The global spread of severe acute respiratory syndrome coronavirus 2 has resulted in a significant number of individuals developing pulmonary fibrosis(PF),an irreversible lung injury.This condition can manifest within...The global spread of severe acute respiratory syndrome coronavirus 2 has resulted in a significant number of individuals developing pulmonary fibrosis(PF),an irreversible lung injury.This condition can manifest within a short inter-val following the onset of pneumonia symptoms,sometimes even within a few days.While lung transplantation is a potentially lifesaving procedure,its limited availability,high costs,intricate surgeries,and risk of immunological rejection present significant drawbacks.The optimal timing of medication administration for coronavirus disease 2019(COVID-19)-induced PF remains controversial.Despite this,it is crucial to explore pharmacotherapy interventions,involving early and preventative treatment as well as pharmacotherapy options for advanced-stage PF.Additionally,studies have demonstrated disparities in anti-fibrotic treatment based on race and gender factors.Genetic mutations may also impact therapeutic efficacy.Enhancing research efforts on pharmacotherapy interventions,while considering relevant pharmacological factors and optimizing the timing and dosage of medication administration,will lead to enhanced,personalized,and fair treatment for individuals impacted by COVID-19-related PF.These measures are crucial in lessening the burden of the disease on healthcare systems and improving patients'quality of life.展开更多
BACKGROUND Development of end-stage renal disease is predominantly attributed to diabetic nephropathy(DN).Previous studies have indicated that myricetin possesses the potential to mitigate the pathological alterations...BACKGROUND Development of end-stage renal disease is predominantly attributed to diabetic nephropathy(DN).Previous studies have indicated that myricetin possesses the potential to mitigate the pathological alterations observed in renal tissue.Never-theless,the precise molecular mechanism through which myricetin influences the progression of DN remains uncertain.AIM To investigate the effects of myricetin on DN and explore its potential therapeutic mechanism.METHODS Db/db mice were administered myricetin intragastrically on a daily basis at doses of 50 mg/kg or 100 mg/kg for a duration of 12 wk.Subsequently,blood and urine indexes were assessed,along with examination of renal tissue pathology.Kidney morphology and fibrosis were evaluated using various staining techniques including hematoxylin and eosin,periodic acid–Schiff,Masson’s trichrome,and Sirius-red.Additionally,high-glucose culturing was conducted on the RAW 264.7 cell line,treated with 25 mM myricetin or co-administered with the PI3K/Akt inhibitor LY294002 for a period of 24 h.In both in vivo and in vitro settings,quantification of inflammation factor levels was conducted using western blotting,real-time qPCR and ELISA.RESULTS In db/db mice,administration of myricetin led to a mitigating effect on DN-induced renal dysfunction and fibrosis.Notably,we observed a significant reduction in expressions of the kidney injury markers kidney injury molecule-1 and neutrophil gelatinase associated lipocalin,along with a decrease in expressions of inflammatory cytokine-related factors.Furthermore,myricetin treatment effectively inhibited the up-regulation of tumor necrosis factor-alpha,interleukin-6,and interluekin-1βinduced by high glucose in RAW 264.7 cells.Additionally,myricetin modulated the M1-type polarization of the RAW 264.7 cells.Molecular docking and bioinformatic analyses revealed Akt as the target of myricetin.The protective effect of myricetin was nullified upon blocking the polarization of RAW 264.7 via inhibition of PI3K/Akt activation using LY294002.CONCLUSION This study demonstrated that myricetin effectively mitigates kidney injury in DN mice through the regulation of macrophage polarization via the PI3K/Akt signaling pathway.展开更多
Background:To explore the effects and mechanisms of Bu-Yang-Huan-Wu Decoction on pulmonary fibrosis in mice.Methods:Forty-five C57BL/6J mice were randomly divided into three groups:Control,Model,and Bu-Yang-Huan-Wu De...Background:To explore the effects and mechanisms of Bu-Yang-Huan-Wu Decoction on pulmonary fibrosis in mice.Methods:Forty-five C57BL/6J mice were randomly divided into three groups:Control,Model,and Bu-Yang-Huan-Wu Decoction.Pulmonary fibrosis was elicited in mice through a solitary intratracheal administration of 2.5 mg/kg bleomycin.For the control group,mice were given a solitary intratracheal administration of a comparable volume of PBS.Treatment began on the first day after the successful model establishment and lasted for 21 days.The survival rate and body weight of the mice were recorded daily,and on the 22nd day,bronchoalveolar lavage fluid was collected to determine total cells and total protein.The wet/dry weight ratio of lung tissue and hydroxyproline were measured.Lung tissue pathology was observed using hematoxylin and eosin staining and Masson staining.The mRNA expression of epithelial-mesenchymal transition-related proteins(E-cadherin and vimentin)was detected by RT-qPCR,and their protein expression was analyzed by western blot.Results:Compared to the model group,the Bu-Yang-Huan-Wu Decoction treatment notably enhanced both the survival rate and body weight in pulmonary fibrosis mice,significantly reduced lung tissue wet/dry weight ratio,total cells,and protein in bronchoalveolar lavage fluid,and hydroxyproline content.The pathological morphology of lung tissue was significantly improved,with increased expression of the epithelial cell marker E-cadherin mRNA and protein,and decreased expression of the mesenchymal cell marker vimentin mRNA and protein.Conclusion:Bu-Yang-Huan-Wu Decoction can improve the degree of bleomycin-induced pulmonary fibrosis in mice by inhibiting epithelial-mesenchymal transition.展开更多
Idiopathic pulmonary fibrosis(IPF),characterized by aggravated alveolar destruc-tion and fibrotic matrix deposition,tendentiously experiences the stage called acute exacerbation IPF(AE-IPF)and progresses to multiple o...Idiopathic pulmonary fibrosis(IPF),characterized by aggravated alveolar destruc-tion and fibrotic matrix deposition,tendentiously experiences the stage called acute exacerbation IPF(AE-IPF)and progresses to multiple organ damage,especially liver injury.Recent studies have found a variety of immune microenvironment disorders associated with elevated IPF risk and secondary organ injury,whereas current animal models induced with bleomycin(BLM)could not completely reflect the pathologi-cal manifestations of AE-IPF patients in clinic,and the exact underlying mechanisms are not yet fully explored.In the current study,we established an AE-IPF model by tracheal administration of a single dose of BLM and then repeated administrations of lipopolysaccharide in mice.This mouse model successfully recapitulated the clinical features of AE-IPF,including excessive intrapulmonary inflammation and fibrosis and extrapulmonary manifestations,as indicated by significant upregulation of Il6,Tnfa,Il1b,Tgfb,fibronectin,and Col1a1 in both lungs and liver and elevated serum aspartate transaminase and alanine transaminase levels.These effects might be attributed to the regulation of Th17 cells.By sharing this novel murine model,we expect to pro-vide an appropriate experimental platform to investigate the pathogenesis of AE-IPF coupled with liver injury and contribute to the discovery and development of targeted interventions.展开更多
Myocardial fibrosis is an important manifestation of diabetic cardiomyopathy.This study investigated the potential mechanism of diabetic myocardial fibrosis.Male C57BL/6J and db/db mice aged 8 weeks were randomly divi...Myocardial fibrosis is an important manifestation of diabetic cardiomyopathy.This study investigated the potential mechanism of diabetic myocardial fibrosis.Male C57BL/6J and db/db mice aged 8 weeks were randomly divided into the diabetic(DB)and control groups.At 20 weeks,the mouse heart was harvested and subjected to hematoxylin-eosin staining(HE)and Masson staining to investigate the degree of fibrosis.The expressions of transforming growth factor-beta 1(TGF-β1),collagen-III,B-cell lymphoma-2(Bcl2),Bcl2-associated X protein(Bax),cleaved gasdermin D(GSDMD),cysteinyl aspartate specific proteinase-1(caspase-1),apoptosis-associated speck-like protein containing a CARD(ASC),and nucleotide-binding oligomerization domain(NOD)-like receptor 3(NLRP3)were measured by western blotting.Immunohistochemistry and TdT-mediated dUTP nick end labeling(TUNEL)staining were performed to analyze the development of apoptosis and pyroptosis.A significant increase in body weight and blood glucose in the DB group was observed.Myocardial pathological injury,fibrosis,apoptosis,and pyroptosis were more obvious and serious in the DB group.The expression of anti-apoptotic Bcl2 significantly decreased,while the expression levels of pro-apoptotic Bax,caspase-3,and pyroptosis-related proteins,such as cleaved GSDMD,and caspase-1 in the DB group were significantly increased.Pyroptosis and apoptosis were probably the main mechanisms that caused myocardial fibrosis in mice with diabetes.展开更多
Objective:To assess the effect of D-pinitol on pulmonary fibrosis induced by bleomycin.Methods:Sprague-Dawley rats received intratracheal bleomycin(6 IU/kg)to induce pulmonary fibrosis,followed by administration of ei...Objective:To assess the effect of D-pinitol on pulmonary fibrosis induced by bleomycin.Methods:Sprague-Dawley rats received intratracheal bleomycin(6 IU/kg)to induce pulmonary fibrosis,followed by administration of either D-pinitol(5,10,or 20 mg/kg)or vehicle or methylprednisolone(10 mg/kg)over 28 days after bleomycin administration.Lung function,biochemical parameters,serum biochemistry,mRNA expressions,and histological features were observed.Results:D-pinitol at 10 and 20 mg/kg significantly(P<0.05)attenuated bleomycin-induced bronchoalveolar lavage fluid,decreased myeloperoxidase,nitric oxide,malondialdehyde levels,and increased glutathione and superoxide dismutase level.D-pinitol also improved lung function(enhanced pause,frequency of breathing,expired volume,and tidal volume).Besides,D-pinitol significantly(P<0.05)upregulated Nrf2 and downregulated mRNA expressions of TGF-β,collagen-1,and Smad-3.Furthermore,considerably less inflammation(peribronchial,perivascular,and total),Ashcroft,and interstitial fibrosis scores were observed in the D-pinitol group.Conclusions:D-pinitol exerts its effect against bleomycin-induced pulmonary fibrosis via antioxidative and anti-fibrotic pathways.展开更多
Objective:To study the protective effect of cannabidiol(CBD)on rats with pulmonary fibrosis and explore the possible mechanism of the use of CBD in the treatment of pulmonary fibrosis.Methods:Sixty SD rats were random...Objective:To study the protective effect of cannabidiol(CBD)on rats with pulmonary fibrosis and explore the possible mechanism of the use of CBD in the treatment of pulmonary fibrosis.Methods:Sixty SD rats were randomly divided into the normal control group,model group,prednisone group,CBD low,medium and high dose groups(12,36,108 mg/kg,ig),10 rats in each group.Except for the normal control group,the other 5 groups were all induced by tracheal injection of bleomycin to rat models of pulmonary fibrosis.After modeling,the rats were given intragastric administration once a day for 28 consecutive days and samples were taken.The degree of pulmonary edema was detected;the pathological changes of lung tissue were observed by HE and Masson staining;tumor necrosis factorα(TNF-α),interleukin-1β(IL-1β),interleukin-6(IL-6)and lung tissue superoxide dismutase(SOD),malondialdehyde(MDA),hydroxyproline(HYP)contents were measured by ELISA,transforming growth factor-β1(TGF-β1)andα-smooth muscle protein(α-SMA)concentration were detected by immunocytochemical method,real-time fluorescent quantitative PCR(qRT-PCR)method was used to detect the mRNA expression levels of TGF-β1,α-SMA,Nrf2 and nuclear transcription factor-κB p65(NF-κB p65).Results:The lung organ coefficient and W/D value were significantly decreased in the CBD administration group(P<0.05);medium and high doses of CBD could reduce the number of collagen fibers and fibroblasts;the pulmonary fibrosis in the low,medium,and high dose groups of CBD was significantly lower.The levels of TNF-α,IL-1β,and IL-6 in rat serum,as well as MDA and HYP in lung tissue,were significantly lower compared to the model group.Additionally,the level of SOD was significantly increased(P<0.05);The expression ofα-SMA was decreased compared with the model group(P<0.05);the contents of TGF-β1,α-SMA and NF-κB p65 mRNA in lung tissue decreased,and the expression level of Nrf2 mRNA increased(P<0.05).Especially,the high-dose group had the most significant effect.Conclusion:CBD can significantly reduce the degree of pulmonary fibrosis in rats,and its potential mechanism may be related to inhibiting inflammatory response,enhancing antioxidant capacity and inhibiting the protein expression of TGF-β1 andα-SMA.展开更多
BACKGROUND Idiopathic pulmonary fibrosis(IPF)is a progressive interstitial lung disease with a high mortality rate.On this basis,exploring potential therapeutic targets to meet the unmet needs of IPF patients is impor...BACKGROUND Idiopathic pulmonary fibrosis(IPF)is a progressive interstitial lung disease with a high mortality rate.On this basis,exploring potential therapeutic targets to meet the unmet needs of IPF patients is important.AIM To explore novel hub genes for IPF therapy.METHODS Here,we used public datasets to identify differentially expressed genes between IPF patients and healthy donors.Potential targets were considered based on multiple bioinformatics analyses,especially the correlation between hub genes and carbon monoxide diffusing capacity of carbon monoxide,forced vital capacity,and patient survival rate.The mRNA levels of the hub genes were determined through quantitative real-time polymerase chain reaction.RESULTS We found that TDO2 was upregulated in IPF patients and predicted poor prognosis.Surprisingly,single-cell RNA sequencing data analysis revealed significant enrichment of TDO2 in alveolar fibroblasts,indicating that TDO2 may participate in the regulation of proliferation and survival.Therefore,we verified the upregulated expression of TDO2 in an experimental mouse model of transforming growth factor-β(TGF-β)-induced pulmonary fibrosis.Furthermore,the results showed that a TDO2 inhibitor effectively suppressed TGF-β-induced fibroblast activation.These findings suggest that TDO2 may be a potential target for IPF treatment.Based on transcription factors-microRNA prediction and scRNA-seq analysis,elevated TDO2 promoted the IPF proliferation of fibroblasts and may be involved in the P53 pathway and aggravate ageing and persistent pulmonary fibrosis.CONCLUSION We provided new target genes prediction and proposed blocking TGF-βproduction as a potential treatment for IPF.展开更多
BACKGROUND Rationale:No other treatment besides lung transplant is effective for idiopathic pulmonary fibrosis(IPF).Patients with IPF have poor prognosis,which may eventually lead to death.Patient concerns:Two female ...BACKGROUND Rationale:No other treatment besides lung transplant is effective for idiopathic pulmonary fibrosis(IPF).Patients with IPF have poor prognosis,which may eventually lead to death.Patient concerns:Two female patients were diagnosed with IPF.In our recent follow-up,both these patients maintained a good quality of life.CASE SUMMARY Diagnosis:Both patients had dry cough and progressive dyspnea.Interventions:The first patient was treated with prednisone,and the second patient was treated with prednisone and tripterygium glycosides.However,the symptoms did not improve and fibrosis was not controlled.Thus,the Feibi recipe was used.Outcomes:No deterioration was observed after the treatment,and the dry cough and its effect were ameliorated.Furthermore,they are still alive and the quality of their lives has improved.CONCLUSION These two cases suggest that the Feibi recipe and other traditional Chinese medicine therapies could be beneficial for IPF treatment.展开更多
Pulmonary fibrosis(PF)is a chronic,progressive,and irreversible pulmonary interstitial disease with unclear pathogenesis.Currently,there are few treatment options for managing PF.Inhalation therapy,as a routine treatm...Pulmonary fibrosis(PF)is a chronic,progressive,and irreversible pulmonary interstitial disease with unclear pathogenesis.Currently,there are few treatment options for managing PF.Inhalation therapy,as a routine treatment for respiratory diseases,is being used to study the treatment of PF.Some herbal medicines and their active ingredients have been reported to have anti-PF effects.This review aims to provide an overview of the latest developments in inhalation therapy,focusing on the utilization of chemical medicines and herbal medicines for the treatment of PF in both clinical practice and basic research.The inhalation of chemical drugs such as pirfenidone,nintedanib,N-acetylcysteine,and interferon-γhas been shown to demonstrate anti-PF effects.Additionally,the inhalation of various natural products derived from herbal medicines,encompassing polyphenols,alkaloids,flavonoids,saponins,terpenoids,and herbal extracts,contributes to the therapeutic management of PF through diverse mechanisms.The inhalation of both chemical and herbal medicines presents promising advantages in the treatment of PF.Further clinical trials are required to investigate the effectiveness,safety,and mechanism of action of inhalation therapy utilizing natural products derived from herbal medicines.展开更多
Objective: To analyze the relevant research literature on the prevention and treatment of pulmonary interstitial fibrosis with traditional Chinese medicine (TCM), understand the current research status, hot spots and ...Objective: To analyze the relevant research literature on the prevention and treatment of pulmonary interstitial fibrosis with traditional Chinese medicine (TCM), understand the current research status, hot spots and future development trend in this field, and provide basis and feasible suggestions for further research in this field. Methods: The journal literatures related to the prevention and treatment of pulmonary interstitial fibrosis with TCM in recent 20 years in CNKI database were searched and passed through CiteSpace 5.8.R3 generates the knowledge map of relevant literature authors, document issuing institutions and keywords, and makes visual analysis. Results: A total of 1,576 documents were included, and the annual number of documents showed a fluctuating upward trend, forming a relatively stable research team represented by authors such as LYU Xiaodong, PANG Lijian and LIU Chuang;According to the atlas of document issuing institutions, Shandong University of Traditional Chinese Medicine and its affiliated hospitals ranked first in the number of documents issued, and the cooperation between institutions is dominated by the University of traditional Chinese medicine and its affiliated hospitals;Keyword cluster analysis shows that a large number of studies have been carried out in the field of etiology and pathogenesis, TCM compound, clinic and experiment. Conclusion: The research on the prevention and treatment of pulmonary interstitial fibrosis with TCM has a high degree of attention, but the cooperation network between the research authors and institutions needs to be strengthened. The research on the pathogenesis and improving the quality of life of patients is the trend of development in the future.展开更多
BACKGROUND In China,the prevalence of type 2 diabetes mellitus(T2DM)among diabetic patients is estimated to be between 90%-95%.Additionally,China is among the 22 countries burdened by a high number of tuberculosis cas...BACKGROUND In China,the prevalence of type 2 diabetes mellitus(T2DM)among diabetic patients is estimated to be between 90%-95%.Additionally,China is among the 22 countries burdened by a high number of tuberculosis cases,with approximately 4.5 million individuals affected by active tuberculosis.Notably,T2DM poses a significant risk factor for the development of tuberculosis,as evidenced by the increased incidence of T2DM coexisting with pulmonary tuberculosis(T2DMPTB),which has risen from 19.3%to 24.1%.It is evident that these two diseases are intricately interconnected and mutually reinforcing in nature.AIM To elucidate the clinical features of individuals diagnosed with both T2DM and tuberculosis(T2DM-PTB),as well as to investigate the potential risk factors associated with active tuberculosis in patients with T2DM.METHODS T2DM-PTB patients who visited our hospital between January 2020 and January 2023 were selected as the observation group,Simple DM patients presenting to our hospital in the same period were the control group,Controls and case groups were matched 1:2 according to the principle of the same sex,age difference(±3)years and disease duration difference(±5)years,patients were investigated for general demographic characteristics,diabetes-related characteristics,body immune status,lifestyle and behavioral habits,univariate and multivariate analysis of the data using conditional logistic regression,calculate the odds ratio(OR)values and 95%CI of OR values.RESULTS A total of 315 study subjects were included in this study,including 105 subjects in the observation group and 210 subjects in the control group.Comparison of the results of both anthropometric and biochemical measures showed that the constitution index,systolic blood pressure,diastolic blood pressure and lymphocyte count were significantly lower in the case group,while fasting blood glucose and high-density lipoprotein cholesterol levels were significantly higher than those in the control group.The results of univariate analysis showed that poor glucose control,hypoproteinemia,lymphopenia,TB contact history,high infection,smoking and alcohol consumption were positively associated with PTB in T2DM patients;married,history of hypertension,treatment of oral hypoglycemic drugs plus insulin,overweight,obesity and regular exercise were negatively associated with PTB in T2DM patients.Results of multivariate stepwise regression analysis found lymphopenia(OR=17.75,95%CI:3.40-92.74),smoking(OR=12.25,95%CI:2.53-59.37),history of TB contact(OR=6.56,95%CI:1.23-35.03)and poor glycemic control(OR=3.37,95%CI:1.11-10.25)was associated with an increased risk of developing PTB in patients with T2DM,While being overweight(OR=0.23,95%CI:0.08-0.72)and obesity(OR=0.11,95%CI:0.02-0.72)was associated with a reduced risk of developing PTB in patients with T2DM.CONCLUSION T2DM-PTB patients are prone to worse glycemic control,higher infection frequency,and a higher proportion of people smoking,drinking alcohol,and lack of exercise.Lymphopenia,smoking,history of TB exposure,poor glycemic control were independent risk factors for T2DM-PTB,and overweight and obesity were associated with reduced risk of concurrent PTB in patients with T2DM.展开更多
Dry powder inhaler Liposomes were prepared to investigate the effectiveness of pulmonary delivery of Colchicine and Budesonide for Idiopathic Pulmonary fibrosis. Budesonide(BUD) and Colchicine(COL) liposomes were prep...Dry powder inhaler Liposomes were prepared to investigate the effectiveness of pulmonary delivery of Colchicine and Budesonide for Idiopathic Pulmonary fibrosis. Budesonide(BUD) and Colchicine(COL) liposomes were prepared by thin layer film hydration method(TFH) using 1,2-Dipalmitoyl-sn-glycero-3-phosphoglycerol sodium(DPPG), Hydrogenated Soyaphosphotidylcholine(HSPC), Soyaphosphatidylcholine(SPC), cholesterol(CHOL) and drug in different weight ratios. The optimum lipid composition for BUD(74.22 ± 0.97%) was DPPG:HSPC: CHOL(4:5:1) and for COL(50.94 ± 2.04%) was DPPG: SPC: CHOL(3:6:1). These compositions retained drug for a longer period of time so selected for further study. Liposomes were found to be spherical in shape with mean size below 100 nm. Liposomes lyophilized using Mannitol as carrier and cryoprotectant showed high entrapment efficiency(97.89-98.6%). The powder was dispersed through an Andersen cascade impactor to evaluate the performance of the aerosolized powder. It was found that prepared liposomal dry powder inhaler(DPIs) sustained the drug release up to 24 hours. Optimized Budesonide DPI Formulation B2(86.53 ± 1.9%), Colchicine DPI Formulation C2(90.54 ± 2.3 %) and BUD and COL DPI Combination M2(89.91 ± 1.8%, 91.23 ± 1.9%). Histopathological results, measurements of lung hydroxyproline content, Myeloperoxidase activity indicated that liposomal drypowder inhaler administration attenuates lung fibrosis induced by bleomycin. Long term stability studies indicated that lyophilised BUD and COL liposomes were stable for 6 months at(25 °C± 2 °C, 60% ± 5% RH) and refrigerated conditions(2-8 °C). These results supported that combination of budesonide and colchicine liposomal dry powder inhaler pulmonary drug delivery for treatment of idiopathic Pulmonary Fibrosis exhibits prolonged drug retention at targeted site and reduces the systemic exposure.展开更多
Diabetic retinopathy(DR) is one of the most important types of diabetic microangiopathy, which is a specific change of fundus lesions and is one of the most serious complications of diabetes. When DR develops to proli...Diabetic retinopathy(DR) is one of the most important types of diabetic microangiopathy, which is a specific change of fundus lesions and is one of the most serious complications of diabetes. When DR develops to proliferative DR, the main factors of decreasing vision, and even blindness, include retinal detachment and vitreous hemorrhage caused by contraction of blood vessels by fiber membrane. Recent studies reported that the formation of fiber vascular membrane is closely related to retinal fibrosis. The connective tissue growth factor(CTGF) is a cytokine that is closely related to DR fibrosis. However, its mechanism is poorly understood. This paper summarizes the recent studies about CTGF on DR fibrosis for a comprehensive understanding of the role and mechanism of CTGF in PDR.展开更多
OBJECTIVE Leukotriene B4(LTB4)biosynthesis and subsequently neutrophilic inflammation may provide a potential strategy for the treatment of acute lung injury(ALI)or idiopathic pulmonary fibrosis(IPF).To provide a pote...OBJECTIVE Leukotriene B4(LTB4)biosynthesis and subsequently neutrophilic inflammation may provide a potential strategy for the treatment of acute lung injury(ALI)or idiopathic pulmonary fibrosis(IPF).To provide a potential strategy for the treatment of ALI or IPF,we identified potent inhibitors of Leukotriene A4 hydrolase(LTA4H),a key enzyme in the biosynthesis of LTB4.METHODS In this study,we identified two known histone deacetylase(HDAC)inhibitors,suberanilohydroxamic acid(SAHA)and its analogue 4-(dimethylamino)-N-[7-(hydroxyamino)-7-oxoheptyl]benzamide(M344),as effective inhibitors of LTA4H using enzymatic assay,thermofluor assay,and X-ray crystallographic investigation.We next tested the effect of SAHA and M344 on endogenous LTB4 biosynthesis in neutrophils by ELISA and neutrophil migration by transwell migration assay.A murine experimental model of ALI was induced by lipopolysaccharide(LPS)inhalation.Histopathological analysis of lung tissue using H&E staining revealed the serious pulmonary damage caused by LPS treatment and the effect of the SAHA.We next examined m RNA and protein levels of pro-inflammatory cytokines in lung tissue and bronchoalveolar lavage fluid using q RT-PCR and ELISA to further investigate the underlying mechanisms of anti-inflammatory activities by SAHA.We also investigated the effects of SAHA and M344 on a murine experimental model of bleomycin(BLM)-induced IPF model.RESULTS The results of enzymatic assay and X-ray crystallography showed that both SAHA and M344 bind to LTA4H,significantly decrease LTB4 levels in neutrophil,and markedly diminish early neutrophilic inflammation in mouse models of ALI and IPF under a clinical safety dose.CONCLUSION Collectively,SAHA and M344 would provide promising agents with well-known clinical safety for potential treatment in patients with ALI and IPF via pharmacologically inhibiting LAT4H and blocking LTB4 biosynthesis.展开更多
AIM: To investigate whether the predominant emphysema type is associated with the high resolution computed tomography(HRCT) pattern of fibrosis in combined pulmonary fibrosis and emphysema(CPFE).METHODS: Fifty-three s...AIM: To investigate whether the predominant emphysema type is associated with the high resolution computed tomography(HRCT) pattern of fibrosis in combined pulmonary fibrosis and emphysema(CPFE).METHODS: Fifty-three smokers with upper lobe emphysema and lower lobe pulmonary fibrosis on- HRCT-were retrospectively evaluated. Patients were stratified into 3 groups according to the predominant type of emphysema: Centrilobular(CLE), paraseptal(PSE), CLE = PSE. Patients were also stratified into 3 other groups according to the predominant type of fibrosis on HRCT: Typical usual interstitial pneumonia(UIP), probable UIP and nonspecific interstitial pneumonia(NSIP). HRCTs were scored at 5 predetermined levels for the coarseness of fibrosis(Coarseness), extent of emphysema(emphysema), extent of interstitial lung disease(Tot Ext ILD), extent of reticular pattern not otherwise specified(Ret NOS), extent of ground glass opacity with traction bronchiectasis(extG GOBx), extent of pure ground glass opacity and extent of honeycombing. HRCT mean scores, pulmonary function tests, diffusion capacity(DLCO) and systolic pulmonary arterial pressure were compared among the groups.RESULTS: The predominant type of emphysema was strongly correlated with the predominant type of fibrosis. The centrilobular emphysema group exhibited a significantly higher extent of emphysema(P < 0.001) and a lower extent of interstitial lung disease(P < 0.002), reticular pattern not otherwise specified(P < 0.023), extent of ground glass opacity with traction bronchiectasis(P < 0.002), extent of honeycombing(P < 0.001) and coarseness of fibrosis(P < 0.001) than the paraseptal group. The NSIP group exhibited a significantly higher extent of emphysema(P < 0.05), total lung capacity(P < 0.01) and diffusion capacity(DLCO)(P < 0.05) than the typical UIP group. The typical UIP group exhibited a significantly higher extent of interstitial lung disease, extent of reticular pattern not otherwise specified, extent of ground glass opacity with traction bronchiectasis, extent of honeycombing and coarseness of fibrosis(0.039 > P > 0.000). Although the pulmonary arterial pressure was higher in typical UIP group relative to the NSIP group, the difference was not statistically significant.CONCLUSION: In CPFE patients, paraseptal emphysema is associated more with UIP-HRCT pattern and higher extent of fibrosis than centrilobular emphysema.展开更多
Rationale: There is accumulating evidence that a group of stem/progenitor cells (SPCs) maintain alveolar epithelial integrity. Pulmonary emphysema is characterized by the histological finding of the loss of alveolar e...Rationale: There is accumulating evidence that a group of stem/progenitor cells (SPCs) maintain alveolar epithelial integrity. Pulmonary emphysema is characterized by the histological finding of the loss of alveolar epithelial integrity along with corresponding bronchiolar fibrosis. Objectives: Based on the concept of autopoiesis (the capacity to produce oneself), we proposed a mathematical model in the maintenance of alveolar epithelial integrity as related to the genesis of pulmonary emphysema and fibrosis. Methods: A tessellation automaton model was used to describe the autopoietic dynamics of the bronchiolo-alveolar epithelial surface. The alveolar septal volume en-closed by the epithelial surface is a distributed system of discrete elements, which move by random walk in the manner of Brownian motion. Assuming that the numbers of components and events in the automaton are large, an approximate theoretical treatment in terms of differential equations is possible, allowing a set of partial differential equations to be produced. Results: 1) Assuming the loss of progenitor cells through the epithelial-mesenchymal transition (EMT), a sharp bifurcation between two qualitatively distinct regions of the phase space (one that is repaired completely, and another that has disappeared entirely) clearly appeared. 2) Thus, from the system of discrete and spatial partial differential equations, we obtained a system of ordinary differential equations in equilibrium conditions that defined a close relationship between the degree of emphysema, the density of alveolar septal fibroblasts, and the mean concentration of SPCs. Conclusions: A mathematical model of the autopoietic maintenance of the alveolar epithelial surface suggested a close relationship between alveolar emphysema and fibrosis and EMT in lungs affected by chronic obstructive pulmonary disease.展开更多
Idiopathic pulmonary fibrosis(IPF)is a serious and fatal pulmonary inflammatory disease with an increasing incidenceworldwide.The drugs nintedanib and pirfenidone,are listed as conditionally recommended drugs in the“...Idiopathic pulmonary fibrosis(IPF)is a serious and fatal pulmonary inflammatory disease with an increasing incidenceworldwide.The drugs nintedanib and pirfenidone,are listed as conditionally recommended drugs in the“Evidence-Based Guidelines for the Diagnosis and Treatment of Idiopathic Pulmonary Fibrosis”.However,these two drugs have many adverse reactions in clinical application.Salvianolic acid B(Sal B),a water-soluble component of Salvia miltiorrhiza,could alleviate bleomycin-induced peroxidative stress damage,and prevent or delay the onset of IPF by regulating inflammatory factors and fibrotic cytokines during the disease’s progression.However,Sal B is poorly absorbed orally,and patient compliance is poor when administered intravenously.Therefore,there is an urgent need to find a new non-injection route of drug delivery.In this study,Sal B was used as model drug and l-leucine(LL)as excipient to prepare Sal B dry powder inhaler(Sal B-DPI)by spray drying method.Modern preparation evaluation methods were used to assess the quality of Sal B-DPI.Sal B-DPI is promising for the treatment of IPF,according to studies on pulmonary irritation evaluation,in vivo and in vitro pharmacodynamics,metabolomics,pharmacokinetics,and lung tissue distribution.展开更多
BACKGROUND Nonalcoholic fatty liver disease(NAFLD)and type-2 diabetes mellitus(T2DM)have an intricate bidirectional relationship.Individuals with T2DM,not only have a higher prevalence of non-alcoholic steatosis,but a...BACKGROUND Nonalcoholic fatty liver disease(NAFLD)and type-2 diabetes mellitus(T2DM)have an intricate bidirectional relationship.Individuals with T2DM,not only have a higher prevalence of non-alcoholic steatosis,but also carry a higher risk of progression to nonalcoholic steatohepatitis.Experts still differ in their recommendations of screening for NAFLD among patients with T2DM.AIM To study the prevalence of NAFLD and advanced fibrosis among our patient population with T2DM.METHODS During the study period(November 2018 to January 2020),59 adult patients with T2DM and 26 non-diabetic control group individuals were recruited prospectively.Patients with known significant liver disease and alcohol use were excluded.Demographic data and lab parameters were recorded.Liver elastography was performed in all patients.RESULTS In the study group comprised of patients with T2DM and normal alanine aminotransferase levels(mean 17.8±7 U/L),81%had hepatic steatosis as diagnosed by elastography.Advanced hepatic fibrosis(stage F3 or F4)was present in 12%of patients with T2DM as compared to none in the control group.Patients with T2DM also had higher number of individuals with grade 3 steatosis[45.8%vs 11.5%,(P<0.00001)and metabolic syndrome(84.7%vs 11.5%,P<0.00001)].CONCLUSION A significant number of patients with T2DM,despite having normal transaminase levels,have NAFLD,grade 3 steatosis and advanced hepatic fibrosis as measured by liver elastography.展开更多
BACKGROUND The prevalence of nonalcoholic fatty liver disease(NAFLD) is significantly rising worldwide. Type-2 diabetes(T2D) is a major risk factor for NAFLD progression.AIM To assess the association of commonly used ...BACKGROUND The prevalence of nonalcoholic fatty liver disease(NAFLD) is significantly rising worldwide. Type-2 diabetes(T2D) is a major risk factor for NAFLD progression.AIM To assess the association of commonly used medications to advanced fibrosis(AF) in patients with biopsy-proven NAFLD and T2D.METHODS We used the International Classification of Disease 9 th Revision Clinical Modification coding system to identify patients with T2D and included patients who underwent liver biopsy for suspected NAFLD between January 1, 2000 to December 31, 2015. We compared demographics, clinical characteristics, and differences in pattern of medication use in patients who had biopsy-proven AF to those without it. A univariate and multivariate analysis was performed to assess the association of different classes of medication with the presence of AF.RESULTS A total of 1183 patients were included in the final analysis, out of which 32%(n =381) had AF on liver biopsy. Mean age of entire cohort was 52 years and majority were females(65%) and Caucasians(85%). Among patients with AF, 51% were on oral hypoglycemics, 30% were on insulin, 66% were on antihypertensives and 27% were on lipid lowering agents for the median duration of 19 mo, 10 mo, 26 mo, and 24 mo respectively. Medications associated with decreased risk of AF included metformin, liraglutide, lisinopril, hydrochlorothiazide, atorvastatin and simvastatin while the use of furosemide and spironolactone were associated with higher prevalence of AF.CONCLUSION In our cohort of T2D with biopsy proven NAFLD, the patients who were receiving metformin, liraglutide, lisinopril, hydrochlorothiazide, atorvastatin and simvastatin were less likely to have AF on biopsy, while patients who were receiving furosemide and spironolactone had a higher likelihood of having AF when they underwent liver biopsy. Future studies are needed to confirm these findings and to establish measures for prevention of NAFLD progression in patients with T2D.展开更多
基金Supported by the Project of Special Funds for Science and Technology Cooperation in Guizhou Provinces and Zunyi City,No.Shengshikehe(2015)53.
文摘The global spread of severe acute respiratory syndrome coronavirus 2 has resulted in a significant number of individuals developing pulmonary fibrosis(PF),an irreversible lung injury.This condition can manifest within a short inter-val following the onset of pneumonia symptoms,sometimes even within a few days.While lung transplantation is a potentially lifesaving procedure,its limited availability,high costs,intricate surgeries,and risk of immunological rejection present significant drawbacks.The optimal timing of medication administration for coronavirus disease 2019(COVID-19)-induced PF remains controversial.Despite this,it is crucial to explore pharmacotherapy interventions,involving early and preventative treatment as well as pharmacotherapy options for advanced-stage PF.Additionally,studies have demonstrated disparities in anti-fibrotic treatment based on race and gender factors.Genetic mutations may also impact therapeutic efficacy.Enhancing research efforts on pharmacotherapy interventions,while considering relevant pharmacological factors and optimizing the timing and dosage of medication administration,will lead to enhanced,personalized,and fair treatment for individuals impacted by COVID-19-related PF.These measures are crucial in lessening the burden of the disease on healthcare systems and improving patients'quality of life.
基金Supported by National Natural Science Foundation of China,No.82205025,No.82374355 and No.82174293Subject of Jiangsu Province Hospital of Chinese Medicine,No.Y21023Forth Batch of Construction Program for Inheritance Office of Jiangsu Province Famous TCM Experts,No.[2021]7.
文摘BACKGROUND Development of end-stage renal disease is predominantly attributed to diabetic nephropathy(DN).Previous studies have indicated that myricetin possesses the potential to mitigate the pathological alterations observed in renal tissue.Never-theless,the precise molecular mechanism through which myricetin influences the progression of DN remains uncertain.AIM To investigate the effects of myricetin on DN and explore its potential therapeutic mechanism.METHODS Db/db mice were administered myricetin intragastrically on a daily basis at doses of 50 mg/kg or 100 mg/kg for a duration of 12 wk.Subsequently,blood and urine indexes were assessed,along with examination of renal tissue pathology.Kidney morphology and fibrosis were evaluated using various staining techniques including hematoxylin and eosin,periodic acid–Schiff,Masson’s trichrome,and Sirius-red.Additionally,high-glucose culturing was conducted on the RAW 264.7 cell line,treated with 25 mM myricetin or co-administered with the PI3K/Akt inhibitor LY294002 for a period of 24 h.In both in vivo and in vitro settings,quantification of inflammation factor levels was conducted using western blotting,real-time qPCR and ELISA.RESULTS In db/db mice,administration of myricetin led to a mitigating effect on DN-induced renal dysfunction and fibrosis.Notably,we observed a significant reduction in expressions of the kidney injury markers kidney injury molecule-1 and neutrophil gelatinase associated lipocalin,along with a decrease in expressions of inflammatory cytokine-related factors.Furthermore,myricetin treatment effectively inhibited the up-regulation of tumor necrosis factor-alpha,interleukin-6,and interluekin-1βinduced by high glucose in RAW 264.7 cells.Additionally,myricetin modulated the M1-type polarization of the RAW 264.7 cells.Molecular docking and bioinformatic analyses revealed Akt as the target of myricetin.The protective effect of myricetin was nullified upon blocking the polarization of RAW 264.7 via inhibition of PI3K/Akt activation using LY294002.CONCLUSION This study demonstrated that myricetin effectively mitigates kidney injury in DN mice through the regulation of macrophage polarization via the PI3K/Akt signaling pathway.
文摘Background:To explore the effects and mechanisms of Bu-Yang-Huan-Wu Decoction on pulmonary fibrosis in mice.Methods:Forty-five C57BL/6J mice were randomly divided into three groups:Control,Model,and Bu-Yang-Huan-Wu Decoction.Pulmonary fibrosis was elicited in mice through a solitary intratracheal administration of 2.5 mg/kg bleomycin.For the control group,mice were given a solitary intratracheal administration of a comparable volume of PBS.Treatment began on the first day after the successful model establishment and lasted for 21 days.The survival rate and body weight of the mice were recorded daily,and on the 22nd day,bronchoalveolar lavage fluid was collected to determine total cells and total protein.The wet/dry weight ratio of lung tissue and hydroxyproline were measured.Lung tissue pathology was observed using hematoxylin and eosin staining and Masson staining.The mRNA expression of epithelial-mesenchymal transition-related proteins(E-cadherin and vimentin)was detected by RT-qPCR,and their protein expression was analyzed by western blot.Results:Compared to the model group,the Bu-Yang-Huan-Wu Decoction treatment notably enhanced both the survival rate and body weight in pulmonary fibrosis mice,significantly reduced lung tissue wet/dry weight ratio,total cells,and protein in bronchoalveolar lavage fluid,and hydroxyproline content.The pathological morphology of lung tissue was significantly improved,with increased expression of the epithelial cell marker E-cadherin mRNA and protein,and decreased expression of the mesenchymal cell marker vimentin mRNA and protein.Conclusion:Bu-Yang-Huan-Wu Decoction can improve the degree of bleomycin-induced pulmonary fibrosis in mice by inhibiting epithelial-mesenchymal transition.
基金supported by the Innovation Team and Talents Cultivation Program of the National Administration of Traditional Chinese Medicine(grant no.:ZYYCXTD-C-202006 to XG and Xiaojiaoyang Li)Beijing Municipal Science and Technology Commission(grant no.:7212174 to Xiaojiaoyang Li)+2 种基金National Natural Science Foundation of China(grant no.:82004045 to Xiaojiaoyang Li)Beijing Nova Program of Science and Technology(grant no.:Z191100001119088 to Xiaojiaoyang Li)the Young Elite Scientists Sponsorship Program by CACM(grant no.:2020-QNRC2-01 to Xiaojiaoyang Li).
文摘Idiopathic pulmonary fibrosis(IPF),characterized by aggravated alveolar destruc-tion and fibrotic matrix deposition,tendentiously experiences the stage called acute exacerbation IPF(AE-IPF)and progresses to multiple organ damage,especially liver injury.Recent studies have found a variety of immune microenvironment disorders associated with elevated IPF risk and secondary organ injury,whereas current animal models induced with bleomycin(BLM)could not completely reflect the pathologi-cal manifestations of AE-IPF patients in clinic,and the exact underlying mechanisms are not yet fully explored.In the current study,we established an AE-IPF model by tracheal administration of a single dose of BLM and then repeated administrations of lipopolysaccharide in mice.This mouse model successfully recapitulated the clinical features of AE-IPF,including excessive intrapulmonary inflammation and fibrosis and extrapulmonary manifestations,as indicated by significant upregulation of Il6,Tnfa,Il1b,Tgfb,fibronectin,and Col1a1 in both lungs and liver and elevated serum aspartate transaminase and alanine transaminase levels.These effects might be attributed to the regulation of Th17 cells.By sharing this novel murine model,we expect to pro-vide an appropriate experimental platform to investigate the pathogenesis of AE-IPF coupled with liver injury and contribute to the discovery and development of targeted interventions.
基金supported by the Advanced Projects of Innovation Program for the Selected Returned Overseas Chinese Scholars,Anhui Province(2020LCX022).
文摘Myocardial fibrosis is an important manifestation of diabetic cardiomyopathy.This study investigated the potential mechanism of diabetic myocardial fibrosis.Male C57BL/6J and db/db mice aged 8 weeks were randomly divided into the diabetic(DB)and control groups.At 20 weeks,the mouse heart was harvested and subjected to hematoxylin-eosin staining(HE)and Masson staining to investigate the degree of fibrosis.The expressions of transforming growth factor-beta 1(TGF-β1),collagen-III,B-cell lymphoma-2(Bcl2),Bcl2-associated X protein(Bax),cleaved gasdermin D(GSDMD),cysteinyl aspartate specific proteinase-1(caspase-1),apoptosis-associated speck-like protein containing a CARD(ASC),and nucleotide-binding oligomerization domain(NOD)-like receptor 3(NLRP3)were measured by western blotting.Immunohistochemistry and TdT-mediated dUTP nick end labeling(TUNEL)staining were performed to analyze the development of apoptosis and pyroptosis.A significant increase in body weight and blood glucose in the DB group was observed.Myocardial pathological injury,fibrosis,apoptosis,and pyroptosis were more obvious and serious in the DB group.The expression of anti-apoptotic Bcl2 significantly decreased,while the expression levels of pro-apoptotic Bax,caspase-3,and pyroptosis-related proteins,such as cleaved GSDMD,and caspase-1 in the DB group were significantly increased.Pyroptosis and apoptosis were probably the main mechanisms that caused myocardial fibrosis in mice with diabetes.
文摘Objective:To assess the effect of D-pinitol on pulmonary fibrosis induced by bleomycin.Methods:Sprague-Dawley rats received intratracheal bleomycin(6 IU/kg)to induce pulmonary fibrosis,followed by administration of either D-pinitol(5,10,or 20 mg/kg)or vehicle or methylprednisolone(10 mg/kg)over 28 days after bleomycin administration.Lung function,biochemical parameters,serum biochemistry,mRNA expressions,and histological features were observed.Results:D-pinitol at 10 and 20 mg/kg significantly(P<0.05)attenuated bleomycin-induced bronchoalveolar lavage fluid,decreased myeloperoxidase,nitric oxide,malondialdehyde levels,and increased glutathione and superoxide dismutase level.D-pinitol also improved lung function(enhanced pause,frequency of breathing,expired volume,and tidal volume).Besides,D-pinitol significantly(P<0.05)upregulated Nrf2 and downregulated mRNA expressions of TGF-β,collagen-1,and Smad-3.Furthermore,considerably less inflammation(peribronchial,perivascular,and total),Ashcroft,and interstitial fibrosis scores were observed in the D-pinitol group.Conclusions:D-pinitol exerts its effect against bleomycin-induced pulmonary fibrosis via antioxidative and anti-fibrotic pathways.
基金Post-doctoral Program of Heilongjiang Province (No.LBH-Z22251)Chinese Medicine Research Project of Heilongjiang Province (No.ZHY2022-114)Heilongjiang Chinese Medicine Association Youth Talent Promotion Project (No.2022-QNRC1-27)。
文摘Objective:To study the protective effect of cannabidiol(CBD)on rats with pulmonary fibrosis and explore the possible mechanism of the use of CBD in the treatment of pulmonary fibrosis.Methods:Sixty SD rats were randomly divided into the normal control group,model group,prednisone group,CBD low,medium and high dose groups(12,36,108 mg/kg,ig),10 rats in each group.Except for the normal control group,the other 5 groups were all induced by tracheal injection of bleomycin to rat models of pulmonary fibrosis.After modeling,the rats were given intragastric administration once a day for 28 consecutive days and samples were taken.The degree of pulmonary edema was detected;the pathological changes of lung tissue were observed by HE and Masson staining;tumor necrosis factorα(TNF-α),interleukin-1β(IL-1β),interleukin-6(IL-6)and lung tissue superoxide dismutase(SOD),malondialdehyde(MDA),hydroxyproline(HYP)contents were measured by ELISA,transforming growth factor-β1(TGF-β1)andα-smooth muscle protein(α-SMA)concentration were detected by immunocytochemical method,real-time fluorescent quantitative PCR(qRT-PCR)method was used to detect the mRNA expression levels of TGF-β1,α-SMA,Nrf2 and nuclear transcription factor-κB p65(NF-κB p65).Results:The lung organ coefficient and W/D value were significantly decreased in the CBD administration group(P<0.05);medium and high doses of CBD could reduce the number of collagen fibers and fibroblasts;the pulmonary fibrosis in the low,medium,and high dose groups of CBD was significantly lower.The levels of TNF-α,IL-1β,and IL-6 in rat serum,as well as MDA and HYP in lung tissue,were significantly lower compared to the model group.Additionally,the level of SOD was significantly increased(P<0.05);The expression ofα-SMA was decreased compared with the model group(P<0.05);the contents of TGF-β1,α-SMA and NF-κB p65 mRNA in lung tissue decreased,and the expression level of Nrf2 mRNA increased(P<0.05).Especially,the high-dose group had the most significant effect.Conclusion:CBD can significantly reduce the degree of pulmonary fibrosis in rats,and its potential mechanism may be related to inhibiting inflammatory response,enhancing antioxidant capacity and inhibiting the protein expression of TGF-β1 andα-SMA.
文摘BACKGROUND Idiopathic pulmonary fibrosis(IPF)is a progressive interstitial lung disease with a high mortality rate.On this basis,exploring potential therapeutic targets to meet the unmet needs of IPF patients is important.AIM To explore novel hub genes for IPF therapy.METHODS Here,we used public datasets to identify differentially expressed genes between IPF patients and healthy donors.Potential targets were considered based on multiple bioinformatics analyses,especially the correlation between hub genes and carbon monoxide diffusing capacity of carbon monoxide,forced vital capacity,and patient survival rate.The mRNA levels of the hub genes were determined through quantitative real-time polymerase chain reaction.RESULTS We found that TDO2 was upregulated in IPF patients and predicted poor prognosis.Surprisingly,single-cell RNA sequencing data analysis revealed significant enrichment of TDO2 in alveolar fibroblasts,indicating that TDO2 may participate in the regulation of proliferation and survival.Therefore,we verified the upregulated expression of TDO2 in an experimental mouse model of transforming growth factor-β(TGF-β)-induced pulmonary fibrosis.Furthermore,the results showed that a TDO2 inhibitor effectively suppressed TGF-β-induced fibroblast activation.These findings suggest that TDO2 may be a potential target for IPF treatment.Based on transcription factors-microRNA prediction and scRNA-seq analysis,elevated TDO2 promoted the IPF proliferation of fibroblasts and may be involved in the P53 pathway and aggravate ageing and persistent pulmonary fibrosis.CONCLUSION We provided new target genes prediction and proposed blocking TGF-βproduction as a potential treatment for IPF.
基金Supported by Beijing Natural Science Foundation,No.7202118National Natural Science Foundation of China,No.81573970and Basic Scientific Research Foundation of Beijing University of Chinese Medicine,No.2021-JYB-XJSJJ-033.
文摘BACKGROUND Rationale:No other treatment besides lung transplant is effective for idiopathic pulmonary fibrosis(IPF).Patients with IPF have poor prognosis,which may eventually lead to death.Patient concerns:Two female patients were diagnosed with IPF.In our recent follow-up,both these patients maintained a good quality of life.CASE SUMMARY Diagnosis:Both patients had dry cough and progressive dyspnea.Interventions:The first patient was treated with prednisone,and the second patient was treated with prednisone and tripterygium glycosides.However,the symptoms did not improve and fibrosis was not controlled.Thus,the Feibi recipe was used.Outcomes:No deterioration was observed after the treatment,and the dry cough and its effect were ameliorated.Furthermore,they are still alive and the quality of their lives has improved.CONCLUSION These two cases suggest that the Feibi recipe and other traditional Chinese medicine therapies could be beneficial for IPF treatment.
基金supported by the National Natural Science Foundation of China under Grant[No.82004141]Guangdong Basic and Applied Basic Research Foundation[No.2023A1515011243]+2 种基金Bao'an Traditional Chinese Medicine Development Foundation under Grant[No.2020KJCX-KTYJ-5,2022KJCX-ZJZL-11]Science,Technology,and Innovation Commission of Shenzhen Municipality under Grant[No.JCYJ20190808160407500]Shenzhen Bao’an Traditional Chinese Medicine Hospital Research Program under Grant[No.BAZYY20220701].
文摘Pulmonary fibrosis(PF)is a chronic,progressive,and irreversible pulmonary interstitial disease with unclear pathogenesis.Currently,there are few treatment options for managing PF.Inhalation therapy,as a routine treatment for respiratory diseases,is being used to study the treatment of PF.Some herbal medicines and their active ingredients have been reported to have anti-PF effects.This review aims to provide an overview of the latest developments in inhalation therapy,focusing on the utilization of chemical medicines and herbal medicines for the treatment of PF in both clinical practice and basic research.The inhalation of chemical drugs such as pirfenidone,nintedanib,N-acetylcysteine,and interferon-γhas been shown to demonstrate anti-PF effects.Additionally,the inhalation of various natural products derived from herbal medicines,encompassing polyphenols,alkaloids,flavonoids,saponins,terpenoids,and herbal extracts,contributes to the therapeutic management of PF through diverse mechanisms.The inhalation of both chemical and herbal medicines presents promising advantages in the treatment of PF.Further clinical trials are required to investigate the effectiveness,safety,and mechanism of action of inhalation therapy utilizing natural products derived from herbal medicines.
基金Key Project of Science and Technology Plan of Shaanxi Province(No.2018ZDXM-SF-008)Construction Project of Famous Traditional Chinese Medicine Ma Zhanping Inheritance Studio(Shaanxi Province Famous Traditional Chinese Medicine Inheritance Studio Construction Project of Shaanxi Province Administration of Traditional Chinese Medicine,studio number:2019013)Ma Zhanping inheritance studio of famous traditional Chinese medicine。
文摘Objective: To analyze the relevant research literature on the prevention and treatment of pulmonary interstitial fibrosis with traditional Chinese medicine (TCM), understand the current research status, hot spots and future development trend in this field, and provide basis and feasible suggestions for further research in this field. Methods: The journal literatures related to the prevention and treatment of pulmonary interstitial fibrosis with TCM in recent 20 years in CNKI database were searched and passed through CiteSpace 5.8.R3 generates the knowledge map of relevant literature authors, document issuing institutions and keywords, and makes visual analysis. Results: A total of 1,576 documents were included, and the annual number of documents showed a fluctuating upward trend, forming a relatively stable research team represented by authors such as LYU Xiaodong, PANG Lijian and LIU Chuang;According to the atlas of document issuing institutions, Shandong University of Traditional Chinese Medicine and its affiliated hospitals ranked first in the number of documents issued, and the cooperation between institutions is dominated by the University of traditional Chinese medicine and its affiliated hospitals;Keyword cluster analysis shows that a large number of studies have been carried out in the field of etiology and pathogenesis, TCM compound, clinic and experiment. Conclusion: The research on the prevention and treatment of pulmonary interstitial fibrosis with TCM has a high degree of attention, but the cooperation network between the research authors and institutions needs to be strengthened. The research on the pathogenesis and improving the quality of life of patients is the trend of development in the future.
文摘BACKGROUND In China,the prevalence of type 2 diabetes mellitus(T2DM)among diabetic patients is estimated to be between 90%-95%.Additionally,China is among the 22 countries burdened by a high number of tuberculosis cases,with approximately 4.5 million individuals affected by active tuberculosis.Notably,T2DM poses a significant risk factor for the development of tuberculosis,as evidenced by the increased incidence of T2DM coexisting with pulmonary tuberculosis(T2DMPTB),which has risen from 19.3%to 24.1%.It is evident that these two diseases are intricately interconnected and mutually reinforcing in nature.AIM To elucidate the clinical features of individuals diagnosed with both T2DM and tuberculosis(T2DM-PTB),as well as to investigate the potential risk factors associated with active tuberculosis in patients with T2DM.METHODS T2DM-PTB patients who visited our hospital between January 2020 and January 2023 were selected as the observation group,Simple DM patients presenting to our hospital in the same period were the control group,Controls and case groups were matched 1:2 according to the principle of the same sex,age difference(±3)years and disease duration difference(±5)years,patients were investigated for general demographic characteristics,diabetes-related characteristics,body immune status,lifestyle and behavioral habits,univariate and multivariate analysis of the data using conditional logistic regression,calculate the odds ratio(OR)values and 95%CI of OR values.RESULTS A total of 315 study subjects were included in this study,including 105 subjects in the observation group and 210 subjects in the control group.Comparison of the results of both anthropometric and biochemical measures showed that the constitution index,systolic blood pressure,diastolic blood pressure and lymphocyte count were significantly lower in the case group,while fasting blood glucose and high-density lipoprotein cholesterol levels were significantly higher than those in the control group.The results of univariate analysis showed that poor glucose control,hypoproteinemia,lymphopenia,TB contact history,high infection,smoking and alcohol consumption were positively associated with PTB in T2DM patients;married,history of hypertension,treatment of oral hypoglycemic drugs plus insulin,overweight,obesity and regular exercise were negatively associated with PTB in T2DM patients.Results of multivariate stepwise regression analysis found lymphopenia(OR=17.75,95%CI:3.40-92.74),smoking(OR=12.25,95%CI:2.53-59.37),history of TB contact(OR=6.56,95%CI:1.23-35.03)and poor glycemic control(OR=3.37,95%CI:1.11-10.25)was associated with an increased risk of developing PTB in patients with T2DM,While being overweight(OR=0.23,95%CI:0.08-0.72)and obesity(OR=0.11,95%CI:0.02-0.72)was associated with a reduced risk of developing PTB in patients with T2DM.CONCLUSION T2DM-PTB patients are prone to worse glycemic control,higher infection frequency,and a higher proportion of people smoking,drinking alcohol,and lack of exercise.Lymphopenia,smoking,history of TB exposure,poor glycemic control were independent risk factors for T2DM-PTB,and overweight and obesity were associated with reduced risk of concurrent PTB in patients with T2DM.
文摘Dry powder inhaler Liposomes were prepared to investigate the effectiveness of pulmonary delivery of Colchicine and Budesonide for Idiopathic Pulmonary fibrosis. Budesonide(BUD) and Colchicine(COL) liposomes were prepared by thin layer film hydration method(TFH) using 1,2-Dipalmitoyl-sn-glycero-3-phosphoglycerol sodium(DPPG), Hydrogenated Soyaphosphotidylcholine(HSPC), Soyaphosphatidylcholine(SPC), cholesterol(CHOL) and drug in different weight ratios. The optimum lipid composition for BUD(74.22 ± 0.97%) was DPPG:HSPC: CHOL(4:5:1) and for COL(50.94 ± 2.04%) was DPPG: SPC: CHOL(3:6:1). These compositions retained drug for a longer period of time so selected for further study. Liposomes were found to be spherical in shape with mean size below 100 nm. Liposomes lyophilized using Mannitol as carrier and cryoprotectant showed high entrapment efficiency(97.89-98.6%). The powder was dispersed through an Andersen cascade impactor to evaluate the performance of the aerosolized powder. It was found that prepared liposomal dry powder inhaler(DPIs) sustained the drug release up to 24 hours. Optimized Budesonide DPI Formulation B2(86.53 ± 1.9%), Colchicine DPI Formulation C2(90.54 ± 2.3 %) and BUD and COL DPI Combination M2(89.91 ± 1.8%, 91.23 ± 1.9%). Histopathological results, measurements of lung hydroxyproline content, Myeloperoxidase activity indicated that liposomal drypowder inhaler administration attenuates lung fibrosis induced by bleomycin. Long term stability studies indicated that lyophilised BUD and COL liposomes were stable for 6 months at(25 °C± 2 °C, 60% ± 5% RH) and refrigerated conditions(2-8 °C). These results supported that combination of budesonide and colchicine liposomal dry powder inhaler pulmonary drug delivery for treatment of idiopathic Pulmonary Fibrosis exhibits prolonged drug retention at targeted site and reduces the systemic exposure.
基金Supported by the National Natural Science Foundation(No.81460089 No.81570872)Tianjin Applied Basic and Frontier Technology Research Plan Project(No.15JCYBJC24900)
文摘Diabetic retinopathy(DR) is one of the most important types of diabetic microangiopathy, which is a specific change of fundus lesions and is one of the most serious complications of diabetes. When DR develops to proliferative DR, the main factors of decreasing vision, and even blindness, include retinal detachment and vitreous hemorrhage caused by contraction of blood vessels by fiber membrane. Recent studies reported that the formation of fiber vascular membrane is closely related to retinal fibrosis. The connective tissue growth factor(CTGF) is a cytokine that is closely related to DR fibrosis. However, its mechanism is poorly understood. This paper summarizes the recent studies about CTGF on DR fibrosis for a comprehensive understanding of the role and mechanism of CTGF in PDR.
基金supported by National Natural Science Foundation of China(81402482,91313303)
文摘OBJECTIVE Leukotriene B4(LTB4)biosynthesis and subsequently neutrophilic inflammation may provide a potential strategy for the treatment of acute lung injury(ALI)or idiopathic pulmonary fibrosis(IPF).To provide a potential strategy for the treatment of ALI or IPF,we identified potent inhibitors of Leukotriene A4 hydrolase(LTA4H),a key enzyme in the biosynthesis of LTB4.METHODS In this study,we identified two known histone deacetylase(HDAC)inhibitors,suberanilohydroxamic acid(SAHA)and its analogue 4-(dimethylamino)-N-[7-(hydroxyamino)-7-oxoheptyl]benzamide(M344),as effective inhibitors of LTA4H using enzymatic assay,thermofluor assay,and X-ray crystallographic investigation.We next tested the effect of SAHA and M344 on endogenous LTB4 biosynthesis in neutrophils by ELISA and neutrophil migration by transwell migration assay.A murine experimental model of ALI was induced by lipopolysaccharide(LPS)inhalation.Histopathological analysis of lung tissue using H&E staining revealed the serious pulmonary damage caused by LPS treatment and the effect of the SAHA.We next examined m RNA and protein levels of pro-inflammatory cytokines in lung tissue and bronchoalveolar lavage fluid using q RT-PCR and ELISA to further investigate the underlying mechanisms of anti-inflammatory activities by SAHA.We also investigated the effects of SAHA and M344 on a murine experimental model of bleomycin(BLM)-induced IPF model.RESULTS The results of enzymatic assay and X-ray crystallography showed that both SAHA and M344 bind to LTA4H,significantly decrease LTB4 levels in neutrophil,and markedly diminish early neutrophilic inflammation in mouse models of ALI and IPF under a clinical safety dose.CONCLUSION Collectively,SAHA and M344 would provide promising agents with well-known clinical safety for potential treatment in patients with ALI and IPF via pharmacologically inhibiting LAT4H and blocking LTB4 biosynthesis.
文摘AIM: To investigate whether the predominant emphysema type is associated with the high resolution computed tomography(HRCT) pattern of fibrosis in combined pulmonary fibrosis and emphysema(CPFE).METHODS: Fifty-three smokers with upper lobe emphysema and lower lobe pulmonary fibrosis on- HRCT-were retrospectively evaluated. Patients were stratified into 3 groups according to the predominant type of emphysema: Centrilobular(CLE), paraseptal(PSE), CLE = PSE. Patients were also stratified into 3 other groups according to the predominant type of fibrosis on HRCT: Typical usual interstitial pneumonia(UIP), probable UIP and nonspecific interstitial pneumonia(NSIP). HRCTs were scored at 5 predetermined levels for the coarseness of fibrosis(Coarseness), extent of emphysema(emphysema), extent of interstitial lung disease(Tot Ext ILD), extent of reticular pattern not otherwise specified(Ret NOS), extent of ground glass opacity with traction bronchiectasis(extG GOBx), extent of pure ground glass opacity and extent of honeycombing. HRCT mean scores, pulmonary function tests, diffusion capacity(DLCO) and systolic pulmonary arterial pressure were compared among the groups.RESULTS: The predominant type of emphysema was strongly correlated with the predominant type of fibrosis. The centrilobular emphysema group exhibited a significantly higher extent of emphysema(P < 0.001) and a lower extent of interstitial lung disease(P < 0.002), reticular pattern not otherwise specified(P < 0.023), extent of ground glass opacity with traction bronchiectasis(P < 0.002), extent of honeycombing(P < 0.001) and coarseness of fibrosis(P < 0.001) than the paraseptal group. The NSIP group exhibited a significantly higher extent of emphysema(P < 0.05), total lung capacity(P < 0.01) and diffusion capacity(DLCO)(P < 0.05) than the typical UIP group. The typical UIP group exhibited a significantly higher extent of interstitial lung disease, extent of reticular pattern not otherwise specified, extent of ground glass opacity with traction bronchiectasis, extent of honeycombing and coarseness of fibrosis(0.039 > P > 0.000). Although the pulmonary arterial pressure was higher in typical UIP group relative to the NSIP group, the difference was not statistically significant.CONCLUSION: In CPFE patients, paraseptal emphysema is associated more with UIP-HRCT pattern and higher extent of fibrosis than centrilobular emphysema.
文摘Rationale: There is accumulating evidence that a group of stem/progenitor cells (SPCs) maintain alveolar epithelial integrity. Pulmonary emphysema is characterized by the histological finding of the loss of alveolar epithelial integrity along with corresponding bronchiolar fibrosis. Objectives: Based on the concept of autopoiesis (the capacity to produce oneself), we proposed a mathematical model in the maintenance of alveolar epithelial integrity as related to the genesis of pulmonary emphysema and fibrosis. Methods: A tessellation automaton model was used to describe the autopoietic dynamics of the bronchiolo-alveolar epithelial surface. The alveolar septal volume en-closed by the epithelial surface is a distributed system of discrete elements, which move by random walk in the manner of Brownian motion. Assuming that the numbers of components and events in the automaton are large, an approximate theoretical treatment in terms of differential equations is possible, allowing a set of partial differential equations to be produced. Results: 1) Assuming the loss of progenitor cells through the epithelial-mesenchymal transition (EMT), a sharp bifurcation between two qualitatively distinct regions of the phase space (one that is repaired completely, and another that has disappeared entirely) clearly appeared. 2) Thus, from the system of discrete and spatial partial differential equations, we obtained a system of ordinary differential equations in equilibrium conditions that defined a close relationship between the degree of emphysema, the density of alveolar septal fibroblasts, and the mean concentration of SPCs. Conclusions: A mathematical model of the autopoietic maintenance of the alveolar epithelial surface suggested a close relationship between alveolar emphysema and fibrosis and EMT in lungs affected by chronic obstructive pulmonary disease.
基金supported by Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine (No. ZYYCXTD-D-202002)Scientific Research Project of Tianjin Municipal Education Commission (No.2019KJ083)
文摘Idiopathic pulmonary fibrosis(IPF)is a serious and fatal pulmonary inflammatory disease with an increasing incidenceworldwide.The drugs nintedanib and pirfenidone,are listed as conditionally recommended drugs in the“Evidence-Based Guidelines for the Diagnosis and Treatment of Idiopathic Pulmonary Fibrosis”.However,these two drugs have many adverse reactions in clinical application.Salvianolic acid B(Sal B),a water-soluble component of Salvia miltiorrhiza,could alleviate bleomycin-induced peroxidative stress damage,and prevent or delay the onset of IPF by regulating inflammatory factors and fibrotic cytokines during the disease’s progression.However,Sal B is poorly absorbed orally,and patient compliance is poor when administered intravenously.Therefore,there is an urgent need to find a new non-injection route of drug delivery.In this study,Sal B was used as model drug and l-leucine(LL)as excipient to prepare Sal B dry powder inhaler(Sal B-DPI)by spray drying method.Modern preparation evaluation methods were used to assess the quality of Sal B-DPI.Sal B-DPI is promising for the treatment of IPF,according to studies on pulmonary irritation evaluation,in vivo and in vitro pharmacodynamics,metabolomics,pharmacokinetics,and lung tissue distribution.
文摘BACKGROUND Nonalcoholic fatty liver disease(NAFLD)and type-2 diabetes mellitus(T2DM)have an intricate bidirectional relationship.Individuals with T2DM,not only have a higher prevalence of non-alcoholic steatosis,but also carry a higher risk of progression to nonalcoholic steatohepatitis.Experts still differ in their recommendations of screening for NAFLD among patients with T2DM.AIM To study the prevalence of NAFLD and advanced fibrosis among our patient population with T2DM.METHODS During the study period(November 2018 to January 2020),59 adult patients with T2DM and 26 non-diabetic control group individuals were recruited prospectively.Patients with known significant liver disease and alcohol use were excluded.Demographic data and lab parameters were recorded.Liver elastography was performed in all patients.RESULTS In the study group comprised of patients with T2DM and normal alanine aminotransferase levels(mean 17.8±7 U/L),81%had hepatic steatosis as diagnosed by elastography.Advanced hepatic fibrosis(stage F3 or F4)was present in 12%of patients with T2DM as compared to none in the control group.Patients with T2DM also had higher number of individuals with grade 3 steatosis[45.8%vs 11.5%,(P<0.00001)and metabolic syndrome(84.7%vs 11.5%,P<0.00001)].CONCLUSION A significant number of patients with T2DM,despite having normal transaminase levels,have NAFLD,grade 3 steatosis and advanced hepatic fibrosis as measured by liver elastography.
文摘BACKGROUND The prevalence of nonalcoholic fatty liver disease(NAFLD) is significantly rising worldwide. Type-2 diabetes(T2D) is a major risk factor for NAFLD progression.AIM To assess the association of commonly used medications to advanced fibrosis(AF) in patients with biopsy-proven NAFLD and T2D.METHODS We used the International Classification of Disease 9 th Revision Clinical Modification coding system to identify patients with T2D and included patients who underwent liver biopsy for suspected NAFLD between January 1, 2000 to December 31, 2015. We compared demographics, clinical characteristics, and differences in pattern of medication use in patients who had biopsy-proven AF to those without it. A univariate and multivariate analysis was performed to assess the association of different classes of medication with the presence of AF.RESULTS A total of 1183 patients were included in the final analysis, out of which 32%(n =381) had AF on liver biopsy. Mean age of entire cohort was 52 years and majority were females(65%) and Caucasians(85%). Among patients with AF, 51% were on oral hypoglycemics, 30% were on insulin, 66% were on antihypertensives and 27% were on lipid lowering agents for the median duration of 19 mo, 10 mo, 26 mo, and 24 mo respectively. Medications associated with decreased risk of AF included metformin, liraglutide, lisinopril, hydrochlorothiazide, atorvastatin and simvastatin while the use of furosemide and spironolactone were associated with higher prevalence of AF.CONCLUSION In our cohort of T2D with biopsy proven NAFLD, the patients who were receiving metformin, liraglutide, lisinopril, hydrochlorothiazide, atorvastatin and simvastatin were less likely to have AF on biopsy, while patients who were receiving furosemide and spironolactone had a higher likelihood of having AF when they underwent liver biopsy. Future studies are needed to confirm these findings and to establish measures for prevention of NAFLD progression in patients with T2D.
