Objective To observe the protection of carbon monoxide （CO） inhalation on lipopolysaccharide （LPS）-induced rat multiple organ injury. Methods Sprague-Dawley rats with multiple organ injury induced by 5 mg/kg LPS i...Objective To observe the protection of carbon monoxide （CO） inhalation on lipopolysaccharide （LPS）-induced rat multiple organ injury. Methods Sprague-Dawley rats with multiple organ injury induced by 5 mg/kg LPS intravenous injection were exposed to room air or 2.5 × 10 ^-4 （V/V） CO for 3 hours. The lung and intestine tissues of rats were harvested to measure the expression of heme oxygenase-1 （ HO-1 ） with reverse transcription-polymerase chain reaction, the levels of pulmonary tumor necrosis factor-or （ TNF-α）, interleukin-6 （ IL-6）, and intestinal platelet activator factor （ PAF）, intercellular adhesion molecule-1 （ICAM-1） with enzyme-linked immunosorbent assay, the content of maleic dialdehyde （MDA） and the activity of myeloperoxidase （MPO） with chemical method, the cell apoptosis rate with flow cytometry, and the pathological changes with light microscope. Results CO inhalation obviously up-regulated the expression of HO-1 in lung （5.43 ± 0. 92） and intestine （6. 29 ± 1.56） in LPS ＋ CO group compared with （ 3.08 ± 0. 82） and （ 3.97 ± 1.16 ） in LPS group （ both P 〈 0. 05 ）. The levels of TNF-ot, IL-6 in lung and PAF, ICAM-1 in intestine ofLPS ＋ CO group were 0. 91 ±0. 25,0. 64 ±0.05, 1. 19 ± 0. 52, and 1.83 ±0. 35 pg/mg, respectively, significantly lower than the corresponding values in LPS group （ 1.48 ± 0. 23, 1.16 ± 0. 26, 1.84 ± 0. 73, and 3.48 ± 0. 36 pg/mg, all P 〈 0. 05 ）. The levels of MDA, MPO, and cell apoptosis rate in lung and intestine of LPS ＋ CO group were 1.02 ± 0. 23 nmol/mg, 1.74 ± 0. 17 nmol/mg, 7.18 ± 1.62 U/mg, 6. 30 ±0. 97 U/mg, 1.60% ±0. 34%, and 30. 56% ±6. 33%, respectively, significantly lower than the corresponding values in LPS group （ 1.27 ± 0. 33 nmol/mg, 2. 75 ± 0. 39 nmol/mg, 8. 16 ± 1.49 U/mg, 7. 72 ± 1.07 U/mg, 3.18% ±0. 51%, and 41.52% -＋3.36%, all P 〈0.05）. In addition, injury of lung and intestine induced by LPS was attenuated at presence of CO inhalation. Conclusion CO inhalation protects rat lung and intestine from LPS-induced injury via anti-oxidantion, anti-inflammation, anti-apoptosis, and up-regulation of HO-1 expression.展开更多
BACKGROUND Bronchopulmonary dysplasia(BPD)is not merely a chronic lung disease,but a systemic condition with multiple organs implications predominantly associated with hyperoxia exposure.Despite advances in current ma...BACKGROUND Bronchopulmonary dysplasia(BPD)is not merely a chronic lung disease,but a systemic condition with multiple organs implications predominantly associated with hyperoxia exposure.Despite advances in current management strategies,limited progress has been made in reducing the BPD-related systemic damage.Meanwhile,although the protective effects of human umbilical cord-derived mesenchymal stem cells(hUC-MSCs)or their exosomes on hyperoxia-induced lung injury have been explored by many researchers,the underlying mechanism has not been addressed in detail,and few studies have focused on the therapeutic effect on systemic multiple organ injury.AIM To investigate whether hUC-MSC intratracheal administration could attenuate hyperoxia-induced lung,heart,and kidney injuries and the underlying regulatory mechanisms.METHODS Neonatal rats were exposed to hyperoxia(80%O_(2)),treated with hUC-MSCs intratracheal(iT)or intraperitoneal(iP)on postnatal day 7,and harvested on postnatal day 21.The tissue sections of the lung,heart,and kidney were analyzed morphometrically.Protein contents of the bronchoalveolar lavage fluid(BALF),myeloper oxidase(MPO)expression,and malondialdehyde(MDA)levels were examined.Pulmonary inflammatory cytokines were measured via enzyme-linked immunosorbent assay.A comparative transcriptomic analysis of differentially expressed genes(DEGs)in lung tissue was conducted via RNA-sequencing.Subsequently,we performed reverse transcription-quantitative polymerase chain reaction and western blot analysis to explore the expression of target mRNA and proteins related to inflammatory and oxidative responses.RESULTS iT hUC-MSCs administration improved pulmonary alveolarization and angiogenesis(P<0.01,P<0.01,P<0.001,and P<0.05 for mean linear intercept,septal counts,vascular medial thickness index,and microvessel density respectively).Meanwhile,treatment with hUC-MSCs iT ameliorated right ventricular hypertrophy(for Fulton’s index,P<0.01),and relieved reduced nephrogenic zone width(P<0.01)and glomerular diameter(P<0.001)in kidneys.Among the beneficial effects,a reduction of BALF protein,MPO,and MDA was observed in hUC-MSCs groups(P<0.01,P<0.001,and P<0.05 respectively).Increased pro-inflammatory cytokines tumor necrosis factor-alpha,interleukin(IL)-1β,and IL-6 expression observed in the hyperoxia group were significantly attenuated by hUC-MSCs administration(P<0.01,P<0.001,and P<0.05 respectively).In addition,we observed an increase in anti-inflammatory cytokine IL-10 expression in rats that received hUC-MSCs iT compared with rats reared in hyperoxia(P<0.05).Transcriptomic analysis showed that the DEGs in lung tissues induced by hyperoxia were enriched in pathways related to inflammatory responses,epithelial cell proliferation,and vasculature development.hUC-MSCs administration blunted these hyperoxia-induced dysregulated genes and resulted in a shift in the gene expression pattern toward the normoxia group.hUC-MSCs increased heme oxygenase-1(HO-1),JAK2,and STAT3 expression,and their phosphorylation in the lung,heart,and kidney(P<0.05).Remarkably,no significant difference was observed between the iT and iP administration.CONCLUSION iT hUC-MSCs administration ameliorates hyperoxia-induced lung,heart,and kidney injuries by activating HO-1 expression and JAK/STAT signaling.The therapeutic benefits of local iT and iP administration are equivalent.展开更多
Summary： The protective effect of erythropoietin （EPO） on tissues following ischemia and reperfusion injuries remains poorly understood. We aimed to investigate the effect of EPO in preventing en- dotoxin-induced o...Summary： The protective effect of erythropoietin （EPO） on tissues following ischemia and reperfusion injuries remains poorly understood. We aimed to investigate the effect of EPO in preventing en- dotoxin-induced organ damage. Rat model of multiple organ failure （MOF） was established by tail vein injection of 10 mg/kg lipopolysaccharide （LPS）. Recombinant human EPO treatment （5000 U/kg） was administered by tail vein injection at 30 min after LPS challenge. Twenty-four h after EPO treatment, changes in serum enzyme levels, including aspartate aminotransferase （AST）, alanine transaminase （ALT）, blood urea nitrogen （BUN） and creatinine （Cr）, were evaluated by biochemical analysis. Serum levels of tumor necrosis factor-tx （TNF-ct） were determined by using immunoradiometric assay. Histological examination of tissue sections was carried out by hematoxylin and eosin staining, while ul- trastructure evaluation of organ tissues was assessed by transmission electron microscopy. Protein ex- pression levels were detected by using Western blotting. EPO treatment showed a modest effect in pre- venting LPS-induced elevation of AST, ALT, BUN, Cr, and TNF-ct levels, and in protecting against LPS-induced tissue degeneration and injured ultrastructure in the lung, liver, and kidney. Moreover, LPS promoted phosphorylation of alanine aminotransferase （AKT） and increased nuclear factor-r,B （NF-rB） activation in the lung, liver, and kidney （P〈0.05 vs. control）. However, EPO treatment significantly de- creased the LPS-induced pAKT up-regulation in these tissues （P〈0.05 vs. LPS treatment alone）. The present study demonstrates that EPO may play a protective role against LPS-induced MOF by reducing the inflammatory response and tissue degeneration, possibly via the phosphatidylinositol 3-kinase/AKT and NF-r,B signaling pathways.展开更多
Background:Sepsis-induced coagulopathy and multiple organ dysfunction syndromes are the leading causes of death in patients with sepsis.Qingwen Baidu decoction(QWBD)can effectively improve the clinical manifestations ...Background:Sepsis-induced coagulopathy and multiple organ dysfunction syndromes are the leading causes of death in patients with sepsis.Qingwen Baidu decoction(QWBD)can effectively improve the clinical manifestations of sepsis and ease inflammation,but its effects on coagulation functions and multiple organ injuries remain unclear.Methods:100 healthy,male Sprague-Dawley rats were randomly divided into the sham group,the cecal ligation and puncture(CLP)group,the low-dose QWBD group,and the high-dose QWBD group,with 25 rats in each group.The sepsis model was established using CLP.Blood was collected to measure platelet count,serum creatinine(Cr),blood urea nitrogen(BUN),alanine aminotransferase(ALT),and aspartate aminotransferase(AST)levels,as well as coagulation function.The total protein in bronchoalveolar lavage fluid(BALF)was determined in each group of rats.The lung,liver,and kidney tissues were harvested,and statistics were calculated on the wet-to-dry(W/D)weight ratio.Changes in histopathology and thrombin level were evaluated in each group.The remaining ten rats in each group were observed daily to record the number of surviving rats.Such observation was made consecutively for 7 days to calculate survival rates.Results:After model establishment,ALT,AST,Cr,and BUN levels were significantly elevated(P<0.01).The BALF protein content and lung W/D weight ratio were significantly increased(P<0.01).Furthermore,the survival rate of rats was significantly reduced in the CLP group compared with the sham group.After the treatment,rats in the high-dose QWBD group had lower ALT(P<0.05),AST(P<0.01),Cr(P<0.05),BUN(P<0.01)levels,lower BALF protein content(P<0.05)and lower lung W/D weight ratio(P<0.01)than the CLP group.However,rats in the high-dose QWBD group had significantly better pathological changes in the lung,liver,and kidney compared to the sham group.After the treatment,the platelet level in the peripheral blood was elevated(P<0.05)and both activated partial thromboplastin time and prothrombin time were significantly shortened(P<0.01).The fibrinogen level was significantly increased(P<0.01).Finally,thrombin positive expression areas in the lung,liver,and kidney were significantly decreased in the high-dose QWBD group.Conclusion:QWBD can improve coagulation disorders caused by sepsis and has a protective effect on multiple organ injuries in rats.展开更多
Dear Editor,A series of novel coronavirus disease 2019(COVID-19)caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)since the end of 2019 is ongoing and triggering a global public health crisis.The es...Dear Editor,A series of novel coronavirus disease 2019(COVID-19)caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)since the end of 2019 is ongoing and triggering a global public health crisis.The estimated case fatality rate is approximately 3.4%in China.However,some patients experience dyspnea within 1 week and develop rapidly to organ injury and even death within 2 weeks after dyspnea.1 In addition,early organ injury could lead to higher risks of mortality.Thus,early identification of patients at risk of organ injury and death is crucial,which saves the patients from classified and invasive treatment,improving clinical outcome and prognosis.The human immune system plays significant roles in the resistance of foreign pathogens and the progress of pneumonia.Recent studies have mentioned that T cells were decreased in COVID-19 patients,excessive activated immune response was caused by pathogenic Th1 cells,and inflammatory CD14+CD16+monocytes may connect to pulmonary immunopathology,leading to deleterious clinical manifestations and even acute mortality after SARS-CoV-2 infections.2 SARS-CoV-2 might damage lymphocytes,especially T lymphocytes,and the immune system was impaired during the period of disease to cause tissue injury.展开更多
Purpose::Rib fractures are one of the most common causes of morbidity and mortality and are associated with abdominal solid organ injury(ASOI).The purpose of this study was to investigate the correlation of ASOI with ...Purpose::Rib fractures are one of the most common causes of morbidity and mortality and are associated with abdominal solid organ injury(ASOI).The purpose of this study was to investigate the correlation of ASOI with the number,location,and involved segments of rib fracture(s)in blunt chest trauma.Methods::This retrospective cohort study was conducted on patients with blunt chest trauma over the age of 15 years,who were hospitalized with the diagnosis of rib fractures from July 2015 to September 2020.After ethic committee approval,a retrospective chart review was designed and patients with a diagnosis of rib fractures were selected.Patients who had chest and abdominopelvic CT scan were included in the study and additional data including age,gender,injury severity score,trauma mechanism,number and sides of the fractured ribs(left/right/bilateral),rib fracture segments(upper,middle,lower zone)and results of chest and abdominal spiral CT scan were recorded.The correlation between ASOI and the sides,segments and number of rib fracture(s)was assessed by Pearson's correlation coefficient.Results::Altogether 1056 patients with rib fracture(s)were included.The mean age was(42.76±13.35)years and 85.4%were male.The most common mechanism of trauma was car accident(34.6%).Most fractures occurred in the middle rib zone(60.44%)and the most commonly involved ribs were the 6th and 7th ones(15.7%and 16.4%,respectively).Concurrent abdominal injuries were observed in 103 patients(34.91%)and were significantly associated with middle zone rib fractures.Conclusion::There is a significant relationship between middle zone rib fractures and ASOI.Intra-abdominal injuries are not restricted to fractures of the lower ribs and thus should always be kept in mind during management of blunt trauma patients with rib fractures.展开更多
AIM:To investigate the impact of intestinal ischemia/reperfusion(I/R) injury and lymph drainage on distant organs in rats.METHODS:Thirty-two Sprague-Dawley male rats,weighing 280-320 g,were randomly divided into blank...AIM:To investigate the impact of intestinal ischemia/reperfusion(I/R) injury and lymph drainage on distant organs in rats.METHODS:Thirty-two Sprague-Dawley male rats,weighing 280-320 g,were randomly divided into blank,sham,I/R,and ischemia/reperfusion and drainage(I/R + D) groups(n = 8).All rats were subjected to 60 min ischemia by clamping the superior mesenteric artery,followed by 120 min reperfusion.The rats in the I/R + D group received intestinal lymph drainage for 180 min.In the sham group,the abdominal cavity was opened for 180 min,but the rats received no treatment.The blank group served as a normal and untreated control.A chromogenic limulus assay kit was used for quantita-tive detection of serum endotoxin.The serum concentrations of tumor necrosis factor-α(TNF-α),interleukin(IL)-6,IL-1β,soluble cell adhesion molecules(sICAM-1),and high mobility group protein box 1(HMGB1) were determined with an enzyme-linked immunosorbent assay kit.Histological evaluations of the intestine,liver,kidney,and lung were performed by hematoxylin and eosin staining and immunohistochemistry.HMGB1 protein expression was assayed by western blot analysis.RESULTS:The serum levels of endotoxin and HMGB1 in the I/R and I/R + D groups were significantly higher than those in the sham group(endotoxin,I/R and I/R + D vs sham:0.033 ± 0.004 EU/mL,0.024 ± 0.003 EU/mL vs 0.017 ± 0.009 EU/mL,respectively,P < 0.05;HMGB1,I/R and I/R + D vs sham:5.473 ± 0.963 EU/mL,4.906 ± 0.552 EU/mL vs 0.476 ± 0.406 EU/mL,respectively,P < 0.05).In addition,endotoxin and HMGB1 were significantly lower in the I/R + D group compared to the I/R group(P < 0.05).The serum inflammatory factors IL-6,IL-1β,and sICAM-1 in the I/R and I/R + D groups were significantly higher than those in the sham group(IL-6,I/R and I/R + D vs sham:41.773 ± 9.753 pg/mL,19.204 ± 4.136 pg/mL vs 11.566 ± 2.973 pg/mL,respectively,P < 0.05;IL-1β,I/R and I/R + D vs sham:144.646 ± 29.378 pg/mL,65.829 ± 10.888 pg/mL vs 38.178 ± 7.157 pg/mL,respectively,P < 0.05;sICAM-1,I/R and I/R + D vs sham:97.360 ± 12.714 ng/mL,48.401 ± 6.547 ng/mL vs 33.073 ± 5.957 ng/mL,respectively;P < 0.05).The serum TNF-α in the I/R group were significantly higher than in the sham group(45.863 ± 11.553 pg/mL vs 18.863 ± 6.679 pg/mL,respectively,P < 0.05).These factors were significantly lower in the I/R + D group compared to the I/R group(P < 0.05).The HMGB1 immunohistochemical staining results showed no staining or apparent injury in the blank group,and slight staining at the top of the microvillus was detected in the sham group.In the I/R group,both the top of villi and the basement membrane were stained for HMGB1 in most areas,and injury in the I/R + D group was less than that in the I/R group.HMGB1 expression in the liver,kidney,and lung of rats in the I/R + D group was significantly lower than the rats in the I/R group(P < 0.05).CONCLUSION:Lymph drainage could block the "gutlymph" pathway,improve intestinal barrier function,and attenuate distant organ injury incurred by intestinal I/R.展开更多
AIM:To study the effect of circulating cell-free oxy-hemoglobin(FHb) on intestinal microcirculation and intestinal epithelial injury in a rat model. METHODS:To induce elevated intravascular circulating FHb,male Spragu...AIM:To study the effect of circulating cell-free oxy-hemoglobin(FHb) on intestinal microcirculation and intestinal epithelial injury in a rat model. METHODS:To induce elevated intravascular circulating FHb,male Sprague-Dawley rats received water or FHb infusion.Microcirculatory changes in jejunum,ileum and colon were evaluated using fluorescent microspheres.Intestinal injury was quantified as plasmatic release of ileal lipid binding protein(iLBP) and verified by histological analysis of the ileum. RESULTS:Water and FHb infusions resulted,when compared with saline infusion,in reduced intestinal microcirculation(after 30 min P<0.05,or better;after 60 min FHb infusion P<0.05 for jejunum and colon) .Circulating FHb levels correlated significantly with release of iLBP(Spearman r=0.72,P=0.0011) .Epithelial cell injury of the villi was histologically observed after water and FHb infusions. CONCLUSION:This study shows that circulating FHb leads to a reduction in intestinal microcirculatory blood flow with marked injury to intestinal epithelial cells. These data support the hypothesis that circulating FHb contributes to the development of intestinal injury.展开更多
Recently, saccharicterpenin extracted from Camellia oleifera seed meal has become a widely used feed supplement in animal husbandry. In order to assess its safety, this study was designed to investigate the toxicity a...Recently, saccharicterpenin extracted from Camellia oleifera seed meal has become a widely used feed supplement in animal husbandry. In order to assess its safety, this study was designed to investigate the toxicity and histopathological effects of saccharicterpenin on piglets. One hundred-fifty weaned pigs((Yorkshire×Landrace)×Duroc), 75 males and 75 females with body weight(BW) of(7.35±0.29) kg, were randomly allotted to groups receiving diets supplemented with 0, 500, 1 000, 2 500 or 5 000 mg kg^–1 saccharicterpenin for 70 d. The diet with 500 mg kg^–1 saccharicterpenin supplementation improved liver glutathione peroxidase(GSH-Px) activity, and the diet with 1 000 mg kg^–1 saccharicterpenin supplementation improved liver glutathione S-transferase(GSH-S) activity in piglets on d 70(P<0.05). At 2 500 mg kg^–1, saccharicterpenin in the diets reduced average daily feed intake(ADFI) and average daily gain(ADG) of piglets from d 1 to 35, damaged the cardiac tissue and liver on d 35, and decreased white blood cell counts(WBC), activities of catalase(CAT) and GSH-Px, and concentrations of glucose(GLU) and urea nitrogen(BUN) in the blood of piglets on d 70(P<0.05). In addition, diets with 5 000 mg kg^–1 saccharicterpenin supplementation reduced ADFI, ADG and increased diarrhea rates of piglets from d 36 to 70, and decreased hemoglobin(HGB) concentration and activity of CAT in the blood of piglets on d 70(P<0.05). Moreover, at a rate of 5 000 mg kg^–1, saccharicterpenin supplementation increased pancreas index on d 35 and hepatic index on d 70, and damaged cardiac tissue, liver and spleen during the whole experimental period(P<0.05). These results suggested that dietary 500 mg kg^–1 saccharicterpenin supplementation had beneficial effects on piglets, but excessive supplementation(2 500 or 5 000 mg kg^–1) of saccharicterpenin in the diets could lead to growth retardation, hematological abnormalities and organ injuries.展开更多
AIM: To identify potential diagnostic target genes in early reperfusion periods following warm liver ischemia before irreversible liver damage occurs. METHODS: We used two strategies (SSH suppression subtractive hybri...AIM: To identify potential diagnostic target genes in early reperfusion periods following warm liver ischemia before irreversible liver damage occurs. METHODS: We used two strategies (SSH suppression subtractive hybridization and hybridization of cDNA arrays) to determine early changes in gene expression profiles in a rat model of partial WI/R, comparing postischemic and adjacent nonischemic liver lobes. Differential gene expression was verified (WI/R; 1 h/2 h) and analyzed in more detail after warm ischemia (1 h) in a reperfusion time kinetics (0, 1, 2 and 6 h) and compared to untreated livers by Northern blot hybridizations. Protein expression was examined on Western blots and by immunohistochemistry for four differentially expressed target genes (Hsp70, Hsp27, Gadd45a and IL-1rI). RESULTS: Thirty-two individual WI/R target genes showing altered RNA levels after confirmation by Northern blot analyzes were identified. Among them, six functionally uncharacteristic expressed sequences and 26 known genes (12 induced in postischemic liver lobes, 14 with higher transcriptional expression in adjacent nonischemic liver lobes). Functional categories of the verified marker genes indicate on the one hand cellular stress and tissue damage but otherwise activation of protective cellular reactions (AP-1 transcription factors, apoptosis related genes, heat shock genes). In order to assign the transcriptional status to the biological relevant protein level we demonstrated that Hsp70, Hsp27, Gadd45a and IL-1rI were clearly up-regulated comparing postischemic and untreated rat livers, suggesting their involvement in the WI/R context. CONCLUSION: This study unveils a WI/R response gene set that will help to explore molecular pathways involved in the tissue damage after WI/R. In addition, these genes especially Hsp70 and Gadd45a might represent promising new candidates indicating WI/R liver damage.展开更多
Optical imaging possesses important implications for early disease diagnosis,timely disease treatment,and basic medical as well as biological research.Compared with the traditionary near-infrared(NIR-I)window(650-950 ...Optical imaging possesses important implications for early disease diagnosis,timely disease treatment,and basic medical as well as biological research.Compared with the traditionary near-infrared(NIR-I)window(650-950 nm)optical imaging,the emerging second near-infrared(NIR-II)window optical imaging technology owns the great superiorities of non-invasiveness,nonionizing radiation,and real-time dynamic imaging with the low biological interference,can significantly improve the tissue penetration depth and detection sensitivity,thus expecting to achieve accurate and precise diagnosis of major diseases.Inspired by the conspicuous superiorities,an increasing number of versatile NIR-II fluorophores have been legitimately designed and engineered for precisely deep-tissue mapping-mediated theranostics of life-threatening diseases.Organic semiconducting nanomaterials(OSNs)are derived from organic conjugated molecules withπ-electron delocalized skeletons,which show greatly preponderant prospects in the biomedicine field due to the excellent photoelectric property,tunable energy bands,and fine biocompatibility.In this review,the superiorities of NIR-II fluorescence imaging using OSNs for brilliant visualization various of diseases,including tongue cancer,ovarian cancer,osteosarcoma,bacteria or pathogens infection,kidney dysfunction,rheumatoid arthritis,liver injury,and cerebrovascular function,are emphatically summarized.Finally,the reasonable prospects and persistent efforts for repurposing OSNs to facilitate the clinical translation of NIR-II fluorescence phototheranostics are outlined.展开更多
Background Apurinic apyrimidinic endonuclease/redox effector factor 1 （APE1/Ref-1） is an important enzyme in the repair of reactive oxygen species-induced DNA damage, and its expression/activation can be induced by ...Background Apurinic apyrimidinic endonuclease/redox effector factor 1 （APE1/Ref-1） is an important enzyme in the repair of reactive oxygen species-induced DNA damage, and its expression/activation can be induced by reactive oxygen species. The aim of this research was to investigate the relationship between multiple-organ injuries and expression of Ref-1 in the early period after liver transplantation. Methods One hundred and fifty adult male Wistar rats were divided randomly into three groups： liver transplantation, sham surgery, and untreated control. After liver transplantation, animals were sacrificed at different time points. Hepatic and renal functions were analyzed by serology. Histology, apoptotic levels, and Ref-1 expression were examined by immunohistochemistry in the liver, kidneys, intestines, and lungs. Results Serum levels of alanine aminotransferase and aspartate aminotransferase peaked 6 hours after liver transplantation and decreased appreciably after 12 hours in the transplantatior~ group, suggesting that the degree of liver injury in the early period after transplantation peaked at 6 hours and then decreased. Pathological analyses showed that hepatic tissues were more severely injured in the transplantation group than in the sham and untreated groups. A considerable number of infiltrating inflammatory cells was observed around the portal vein in the transplantation group. Injuries to the kidneys, intestines, and lungs were milder after liver transplantation. Apoptotic levels increased after liver transplantation in all four organs examined. Ref-1 expression was higher in the transplantation group in the early period after liver transplantation than in the sham surgery and untreated control groups. Conclusion Ref-1 expression induced by ischemia-reperfusion injury may have a critical role in repairing multiple-organ injuries after liver transplantation.展开更多
Severe acute pancreatitis(SAP)is a life-threatening acute abdominal disease with two peaks of death:the first in the early stage,characterized by systemic inflammatory response-associated organ failure;and the second ...Severe acute pancreatitis(SAP)is a life-threatening acute abdominal disease with two peaks of death:the first in the early stage,characterized by systemic inflammatory response-associated organ failure;and the second in the late stage,characterized by infectious complications.Neutrophils are the main immune cells participating in the whole process of SAP.In addition to the traditional recognition of neutrophils as the origination of chemokine and cytokine cascades or phagocytosis and degranulation of pathogens,neutrophil extracellular traps(NETs)also play an important roles in inflammatory reactions.We reviewed the role of NETs in the occurrence and development of SAP and its fatal complications,including multiple organs injury,infected pancreatic necrosis,and thrombosis.This review provides novel insights into the involvement of NETs throughout the entire process of SAP,showing that targeting NETs might be a promising strategy in SAP treatment.However,precision therapeutic options targeting NETs in different situations require further investigation.展开更多
The kidneys have a close functional relationship with other organs especially the lungs. This connection makes the kidney and the lungs as the most organs involved in the multi-organ failure syndrome. The combination ...The kidneys have a close functional relationship with other organs especially the lungs. This connection makes the kidney and the lungs as the most organs involved in the multi-organ failure syndrome. The combination of acute lung injury （ALl） and renal failure results a great clinical significance of 80% mortality rate. Acute kidney injury （AKI） leads to an increase in circulating cytokines, chemokines, activated innate immune cells and diffuse of these agents to other organs such as the lungs. These factors initiate pathological cascade that ultimately leads to ALl and acute respiratory distress syndrome （ARDS）. We comprehensively searched the English medical literature focusing on AKI, ALl, organs cross talk, renal failure, multi organ failure and ARDS using the databases of PubMed, Embase, Scopus and directory of open access journals. In this narrative review, we summarized the pathophysiology and treatment of respiratory distress syndrome following AKI. This review promotes knowledge of the link between kidney and lung with mechanisms, diagnostic biomarkers, and treatment involved ARDS induced by AKI.展开更多
文摘Objective To observe the protection of carbon monoxide （CO） inhalation on lipopolysaccharide （LPS）-induced rat multiple organ injury. Methods Sprague-Dawley rats with multiple organ injury induced by 5 mg/kg LPS intravenous injection were exposed to room air or 2.5 × 10 ^-4 （V/V） CO for 3 hours. The lung and intestine tissues of rats were harvested to measure the expression of heme oxygenase-1 （ HO-1 ） with reverse transcription-polymerase chain reaction, the levels of pulmonary tumor necrosis factor-or （ TNF-α）, interleukin-6 （ IL-6）, and intestinal platelet activator factor （ PAF）, intercellular adhesion molecule-1 （ICAM-1） with enzyme-linked immunosorbent assay, the content of maleic dialdehyde （MDA） and the activity of myeloperoxidase （MPO） with chemical method, the cell apoptosis rate with flow cytometry, and the pathological changes with light microscope. Results CO inhalation obviously up-regulated the expression of HO-1 in lung （5.43 ± 0. 92） and intestine （6. 29 ± 1.56） in LPS ＋ CO group compared with （ 3.08 ± 0. 82） and （ 3.97 ± 1.16 ） in LPS group （ both P 〈 0. 05 ）. The levels of TNF-ot, IL-6 in lung and PAF, ICAM-1 in intestine ofLPS ＋ CO group were 0. 91 ±0. 25,0. 64 ±0.05, 1. 19 ± 0. 52, and 1.83 ±0. 35 pg/mg, respectively, significantly lower than the corresponding values in LPS group （ 1.48 ± 0. 23, 1.16 ± 0. 26, 1.84 ± 0. 73, and 3.48 ± 0. 36 pg/mg, all P 〈 0. 05 ）. The levels of MDA, MPO, and cell apoptosis rate in lung and intestine of LPS ＋ CO group were 1.02 ± 0. 23 nmol/mg, 1.74 ± 0. 17 nmol/mg, 7.18 ± 1.62 U/mg, 6. 30 ±0. 97 U/mg, 1.60% ±0. 34%, and 30. 56% ±6. 33%, respectively, significantly lower than the corresponding values in LPS group （ 1.27 ± 0. 33 nmol/mg, 2. 75 ± 0. 39 nmol/mg, 8. 16 ± 1.49 U/mg, 7. 72 ± 1.07 U/mg, 3.18% ±0. 51%, and 41.52% -＋3.36%, all P 〈0.05）. In addition, injury of lung and intestine induced by LPS was attenuated at presence of CO inhalation. Conclusion CO inhalation protects rat lung and intestine from LPS-induced injury via anti-oxidantion, anti-inflammation, anti-apoptosis, and up-regulation of HO-1 expression.
基金Supported by Rongxiang Regenerative Medicine Foundation of Shandong University, No. 2019SDRX-18Clinical Practical New Technology Development Found of Qilu Hospital of Shandong University, No. KYC 2019-0057+1 种基金Clinical Research Center of Shandong University, No. 2020SDUCRCA010Natural Science Foundation of Shandong Province, No. ZR2020MH063
文摘BACKGROUND Bronchopulmonary dysplasia(BPD)is not merely a chronic lung disease,but a systemic condition with multiple organs implications predominantly associated with hyperoxia exposure.Despite advances in current management strategies,limited progress has been made in reducing the BPD-related systemic damage.Meanwhile,although the protective effects of human umbilical cord-derived mesenchymal stem cells(hUC-MSCs)or their exosomes on hyperoxia-induced lung injury have been explored by many researchers,the underlying mechanism has not been addressed in detail,and few studies have focused on the therapeutic effect on systemic multiple organ injury.AIM To investigate whether hUC-MSC intratracheal administration could attenuate hyperoxia-induced lung,heart,and kidney injuries and the underlying regulatory mechanisms.METHODS Neonatal rats were exposed to hyperoxia(80%O_(2)),treated with hUC-MSCs intratracheal(iT)or intraperitoneal(iP)on postnatal day 7,and harvested on postnatal day 21.The tissue sections of the lung,heart,and kidney were analyzed morphometrically.Protein contents of the bronchoalveolar lavage fluid(BALF),myeloper oxidase(MPO)expression,and malondialdehyde(MDA)levels were examined.Pulmonary inflammatory cytokines were measured via enzyme-linked immunosorbent assay.A comparative transcriptomic analysis of differentially expressed genes(DEGs)in lung tissue was conducted via RNA-sequencing.Subsequently,we performed reverse transcription-quantitative polymerase chain reaction and western blot analysis to explore the expression of target mRNA and proteins related to inflammatory and oxidative responses.RESULTS iT hUC-MSCs administration improved pulmonary alveolarization and angiogenesis(P<0.01,P<0.01,P<0.001,and P<0.05 for mean linear intercept,septal counts,vascular medial thickness index,and microvessel density respectively).Meanwhile,treatment with hUC-MSCs iT ameliorated right ventricular hypertrophy(for Fulton’s index,P<0.01),and relieved reduced nephrogenic zone width(P<0.01)and glomerular diameter(P<0.001)in kidneys.Among the beneficial effects,a reduction of BALF protein,MPO,and MDA was observed in hUC-MSCs groups(P<0.01,P<0.001,and P<0.05 respectively).Increased pro-inflammatory cytokines tumor necrosis factor-alpha,interleukin(IL)-1β,and IL-6 expression observed in the hyperoxia group were significantly attenuated by hUC-MSCs administration(P<0.01,P<0.001,and P<0.05 respectively).In addition,we observed an increase in anti-inflammatory cytokine IL-10 expression in rats that received hUC-MSCs iT compared with rats reared in hyperoxia(P<0.05).Transcriptomic analysis showed that the DEGs in lung tissues induced by hyperoxia were enriched in pathways related to inflammatory responses,epithelial cell proliferation,and vasculature development.hUC-MSCs administration blunted these hyperoxia-induced dysregulated genes and resulted in a shift in the gene expression pattern toward the normoxia group.hUC-MSCs increased heme oxygenase-1(HO-1),JAK2,and STAT3 expression,and their phosphorylation in the lung,heart,and kidney(P<0.05).Remarkably,no significant difference was observed between the iT and iP administration.CONCLUSION iT hUC-MSCs administration ameliorates hyperoxia-induced lung,heart,and kidney injuries by activating HO-1 expression and JAK/STAT signaling.The therapeutic benefits of local iT and iP administration are equivalent.
基金supported by Foundation of Health Department of Jilin Province(No.2009Z072)
文摘Summary： The protective effect of erythropoietin （EPO） on tissues following ischemia and reperfusion injuries remains poorly understood. We aimed to investigate the effect of EPO in preventing en- dotoxin-induced organ damage. Rat model of multiple organ failure （MOF） was established by tail vein injection of 10 mg/kg lipopolysaccharide （LPS）. Recombinant human EPO treatment （5000 U/kg） was administered by tail vein injection at 30 min after LPS challenge. Twenty-four h after EPO treatment, changes in serum enzyme levels, including aspartate aminotransferase （AST）, alanine transaminase （ALT）, blood urea nitrogen （BUN） and creatinine （Cr）, were evaluated by biochemical analysis. Serum levels of tumor necrosis factor-tx （TNF-ct） were determined by using immunoradiometric assay. Histological examination of tissue sections was carried out by hematoxylin and eosin staining, while ul- trastructure evaluation of organ tissues was assessed by transmission electron microscopy. Protein ex- pression levels were detected by using Western blotting. EPO treatment showed a modest effect in pre- venting LPS-induced elevation of AST, ALT, BUN, Cr, and TNF-ct levels, and in protecting against LPS-induced tissue degeneration and injured ultrastructure in the lung, liver, and kidney. Moreover, LPS promoted phosphorylation of alanine aminotransferase （AKT） and increased nuclear factor-r,B （NF-rB） activation in the lung, liver, and kidney （P〈0.05 vs. control）. However, EPO treatment significantly de- creased the LPS-induced pAKT up-regulation in these tissues （P〈0.05 vs. LPS treatment alone）. The present study demonstrates that EPO may play a protective role against LPS-induced MOF by reducing the inflammatory response and tissue degeneration, possibly via the phosphatidylinositol 3-kinase/AKT and NF-r,B signaling pathways.
基金supported by the National Key R&D Program of China(No.2018YFC1706500Nos.81973800)+3 种基金the Tianjin Scientific Research Project of Priority Area of Traditional Chinese Medicine(No.20170062022007)the Oncology Translational Medicine Seed Fund Project of Tianjin Medical University Cancer Hospital(No.1910)the Chunmiao Project of Tianjin First Center Hospital(No.2019CM15).
文摘Background:Sepsis-induced coagulopathy and multiple organ dysfunction syndromes are the leading causes of death in patients with sepsis.Qingwen Baidu decoction(QWBD)can effectively improve the clinical manifestations of sepsis and ease inflammation,but its effects on coagulation functions and multiple organ injuries remain unclear.Methods:100 healthy,male Sprague-Dawley rats were randomly divided into the sham group,the cecal ligation and puncture(CLP)group,the low-dose QWBD group,and the high-dose QWBD group,with 25 rats in each group.The sepsis model was established using CLP.Blood was collected to measure platelet count,serum creatinine(Cr),blood urea nitrogen(BUN),alanine aminotransferase(ALT),and aspartate aminotransferase(AST)levels,as well as coagulation function.The total protein in bronchoalveolar lavage fluid(BALF)was determined in each group of rats.The lung,liver,and kidney tissues were harvested,and statistics were calculated on the wet-to-dry(W/D)weight ratio.Changes in histopathology and thrombin level were evaluated in each group.The remaining ten rats in each group were observed daily to record the number of surviving rats.Such observation was made consecutively for 7 days to calculate survival rates.Results:After model establishment,ALT,AST,Cr,and BUN levels were significantly elevated(P<0.01).The BALF protein content and lung W/D weight ratio were significantly increased(P<0.01).Furthermore,the survival rate of rats was significantly reduced in the CLP group compared with the sham group.After the treatment,rats in the high-dose QWBD group had lower ALT(P<0.05),AST(P<0.01),Cr(P<0.05),BUN(P<0.01)levels,lower BALF protein content(P<0.05)and lower lung W/D weight ratio(P<0.01)than the CLP group.However,rats in the high-dose QWBD group had significantly better pathological changes in the lung,liver,and kidney compared to the sham group.After the treatment,the platelet level in the peripheral blood was elevated(P<0.05)and both activated partial thromboplastin time and prothrombin time were significantly shortened(P<0.01).The fibrinogen level was significantly increased(P<0.01).Finally,thrombin positive expression areas in the lung,liver,and kidney were significantly decreased in the high-dose QWBD group.Conclusion:QWBD can improve coagulation disorders caused by sepsis and has a protective effect on multiple organ injuries in rats.
文摘Dear Editor,A series of novel coronavirus disease 2019(COVID-19)caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)since the end of 2019 is ongoing and triggering a global public health crisis.The estimated case fatality rate is approximately 3.4%in China.However,some patients experience dyspnea within 1 week and develop rapidly to organ injury and even death within 2 weeks after dyspnea.1 In addition,early organ injury could lead to higher risks of mortality.Thus,early identification of patients at risk of organ injury and death is crucial,which saves the patients from classified and invasive treatment,improving clinical outcome and prognosis.The human immune system plays significant roles in the resistance of foreign pathogens and the progress of pneumonia.Recent studies have mentioned that T cells were decreased in COVID-19 patients,excessive activated immune response was caused by pathogenic Th1 cells,and inflammatory CD14+CD16+monocytes may connect to pulmonary immunopathology,leading to deleterious clinical manifestations and even acute mortality after SARS-CoV-2 infections.2 SARS-CoV-2 might damage lymphocytes,especially T lymphocytes,and the immune system was impaired during the period of disease to cause tissue injury.
文摘Purpose::Rib fractures are one of the most common causes of morbidity and mortality and are associated with abdominal solid organ injury(ASOI).The purpose of this study was to investigate the correlation of ASOI with the number,location,and involved segments of rib fracture(s)in blunt chest trauma.Methods::This retrospective cohort study was conducted on patients with blunt chest trauma over the age of 15 years,who were hospitalized with the diagnosis of rib fractures from July 2015 to September 2020.After ethic committee approval,a retrospective chart review was designed and patients with a diagnosis of rib fractures were selected.Patients who had chest and abdominopelvic CT scan were included in the study and additional data including age,gender,injury severity score,trauma mechanism,number and sides of the fractured ribs(left/right/bilateral),rib fracture segments(upper,middle,lower zone)and results of chest and abdominal spiral CT scan were recorded.The correlation between ASOI and the sides,segments and number of rib fracture(s)was assessed by Pearson's correlation coefficient.Results::Altogether 1056 patients with rib fracture(s)were included.The mean age was(42.76±13.35)years and 85.4%were male.The most common mechanism of trauma was car accident(34.6%).Most fractures occurred in the middle rib zone(60.44%)and the most commonly involved ribs were the 6th and 7th ones(15.7%and 16.4%,respectively).Concurrent abdominal injuries were observed in 103 patients(34.91%)and were significantly associated with middle zone rib fractures.Conclusion::There is a significant relationship between middle zone rib fractures and ASOI.Intra-abdominal injuries are not restricted to fractures of the lower ribs and thus should always be kept in mind during management of blunt trauma patients with rib fractures.
基金Supported by The National Natural Science Foundation of China,No. 30940069the Natural Sciences Foundation of Beijing,No. 7102127
文摘AIM:To investigate the impact of intestinal ischemia/reperfusion(I/R) injury and lymph drainage on distant organs in rats.METHODS:Thirty-two Sprague-Dawley male rats,weighing 280-320 g,were randomly divided into blank,sham,I/R,and ischemia/reperfusion and drainage(I/R + D) groups(n = 8).All rats were subjected to 60 min ischemia by clamping the superior mesenteric artery,followed by 120 min reperfusion.The rats in the I/R + D group received intestinal lymph drainage for 180 min.In the sham group,the abdominal cavity was opened for 180 min,but the rats received no treatment.The blank group served as a normal and untreated control.A chromogenic limulus assay kit was used for quantita-tive detection of serum endotoxin.The serum concentrations of tumor necrosis factor-α(TNF-α),interleukin(IL)-6,IL-1β,soluble cell adhesion molecules(sICAM-1),and high mobility group protein box 1(HMGB1) were determined with an enzyme-linked immunosorbent assay kit.Histological evaluations of the intestine,liver,kidney,and lung were performed by hematoxylin and eosin staining and immunohistochemistry.HMGB1 protein expression was assayed by western blot analysis.RESULTS:The serum levels of endotoxin and HMGB1 in the I/R and I/R + D groups were significantly higher than those in the sham group(endotoxin,I/R and I/R + D vs sham:0.033 ± 0.004 EU/mL,0.024 ± 0.003 EU/mL vs 0.017 ± 0.009 EU/mL,respectively,P < 0.05;HMGB1,I/R and I/R + D vs sham:5.473 ± 0.963 EU/mL,4.906 ± 0.552 EU/mL vs 0.476 ± 0.406 EU/mL,respectively,P < 0.05).In addition,endotoxin and HMGB1 were significantly lower in the I/R + D group compared to the I/R group(P < 0.05).The serum inflammatory factors IL-6,IL-1β,and sICAM-1 in the I/R and I/R + D groups were significantly higher than those in the sham group(IL-6,I/R and I/R + D vs sham:41.773 ± 9.753 pg/mL,19.204 ± 4.136 pg/mL vs 11.566 ± 2.973 pg/mL,respectively,P < 0.05;IL-1β,I/R and I/R + D vs sham:144.646 ± 29.378 pg/mL,65.829 ± 10.888 pg/mL vs 38.178 ± 7.157 pg/mL,respectively,P < 0.05;sICAM-1,I/R and I/R + D vs sham:97.360 ± 12.714 ng/mL,48.401 ± 6.547 ng/mL vs 33.073 ± 5.957 ng/mL,respectively;P < 0.05).The serum TNF-α in the I/R group were significantly higher than in the sham group(45.863 ± 11.553 pg/mL vs 18.863 ± 6.679 pg/mL,respectively,P < 0.05).These factors were significantly lower in the I/R + D group compared to the I/R group(P < 0.05).The HMGB1 immunohistochemical staining results showed no staining or apparent injury in the blank group,and slight staining at the top of the microvillus was detected in the sham group.In the I/R group,both the top of villi and the basement membrane were stained for HMGB1 in most areas,and injury in the I/R + D group was less than that in the I/R group.HMGB1 expression in the liver,kidney,and lung of rats in the I/R + D group was significantly lower than the rats in the I/R group(P < 0.05).CONCLUSION:Lymph drainage could block the "gutlymph" pathway,improve intestinal barrier function,and attenuate distant organ injury incurred by intestinal I/R.
基金Supported by The Profileringsfonds of the Maastricht University Medical Center(to Jacobs MJ and Buurman WA)an AGIKO-stipendium 920-03-522(to Lubbers T)from The Netherlands Organization for Health Research and Development
文摘AIM:To study the effect of circulating cell-free oxy-hemoglobin(FHb) on intestinal microcirculation and intestinal epithelial injury in a rat model. METHODS:To induce elevated intravascular circulating FHb,male Sprague-Dawley rats received water or FHb infusion.Microcirculatory changes in jejunum,ileum and colon were evaluated using fluorescent microspheres.Intestinal injury was quantified as plasmatic release of ileal lipid binding protein(iLBP) and verified by histological analysis of the ileum. RESULTS:Water and FHb infusions resulted,when compared with saline infusion,in reduced intestinal microcirculation(after 30 min P<0.05,or better;after 60 min FHb infusion P<0.05 for jejunum and colon) .Circulating FHb levels correlated significantly with release of iLBP(Spearman r=0.72,P=0.0011) .Epithelial cell injury of the villi was histologically observed after water and FHb infusions. CONCLUSION:This study shows that circulating FHb leads to a reduction in intestinal microcirculatory blood flow with marked injury to intestinal epithelial cells. These data support the hypothesis that circulating FHb contributes to the development of intestinal injury.
基金financially supported by the earmarked fund for China Agriculture Research System (CARS-35)a grant from the Science and Technology Support Project of Sichuan Province, China (2016NYZ0052)
文摘Recently, saccharicterpenin extracted from Camellia oleifera seed meal has become a widely used feed supplement in animal husbandry. In order to assess its safety, this study was designed to investigate the toxicity and histopathological effects of saccharicterpenin on piglets. One hundred-fifty weaned pigs((Yorkshire×Landrace)×Duroc), 75 males and 75 females with body weight(BW) of(7.35±0.29) kg, were randomly allotted to groups receiving diets supplemented with 0, 500, 1 000, 2 500 or 5 000 mg kg^–1 saccharicterpenin for 70 d. The diet with 500 mg kg^–1 saccharicterpenin supplementation improved liver glutathione peroxidase(GSH-Px) activity, and the diet with 1 000 mg kg^–1 saccharicterpenin supplementation improved liver glutathione S-transferase(GSH-S) activity in piglets on d 70(P<0.05). At 2 500 mg kg^–1, saccharicterpenin in the diets reduced average daily feed intake(ADFI) and average daily gain(ADG) of piglets from d 1 to 35, damaged the cardiac tissue and liver on d 35, and decreased white blood cell counts(WBC), activities of catalase(CAT) and GSH-Px, and concentrations of glucose(GLU) and urea nitrogen(BUN) in the blood of piglets on d 70(P<0.05). In addition, diets with 5 000 mg kg^–1 saccharicterpenin supplementation reduced ADFI, ADG and increased diarrhea rates of piglets from d 36 to 70, and decreased hemoglobin(HGB) concentration and activity of CAT in the blood of piglets on d 70(P<0.05). Moreover, at a rate of 5 000 mg kg^–1, saccharicterpenin supplementation increased pancreas index on d 35 and hepatic index on d 70, and damaged cardiac tissue, liver and spleen during the whole experimental period(P<0.05). These results suggested that dietary 500 mg kg^–1 saccharicterpenin supplementation had beneficial effects on piglets, but excessive supplementation(2 500 or 5 000 mg kg^–1) of saccharicterpenin in the diets could lead to growth retardation, hematological abnormalities and organ injuries.
文摘AIM: To identify potential diagnostic target genes in early reperfusion periods following warm liver ischemia before irreversible liver damage occurs. METHODS: We used two strategies (SSH suppression subtractive hybridization and hybridization of cDNA arrays) to determine early changes in gene expression profiles in a rat model of partial WI/R, comparing postischemic and adjacent nonischemic liver lobes. Differential gene expression was verified (WI/R; 1 h/2 h) and analyzed in more detail after warm ischemia (1 h) in a reperfusion time kinetics (0, 1, 2 and 6 h) and compared to untreated livers by Northern blot hybridizations. Protein expression was examined on Western blots and by immunohistochemistry for four differentially expressed target genes (Hsp70, Hsp27, Gadd45a and IL-1rI). RESULTS: Thirty-two individual WI/R target genes showing altered RNA levels after confirmation by Northern blot analyzes were identified. Among them, six functionally uncharacteristic expressed sequences and 26 known genes (12 induced in postischemic liver lobes, 14 with higher transcriptional expression in adjacent nonischemic liver lobes). Functional categories of the verified marker genes indicate on the one hand cellular stress and tissue damage but otherwise activation of protective cellular reactions (AP-1 transcription factors, apoptosis related genes, heat shock genes). In order to assign the transcriptional status to the biological relevant protein level we demonstrated that Hsp70, Hsp27, Gadd45a and IL-1rI were clearly up-regulated comparing postischemic and untreated rat livers, suggesting their involvement in the WI/R context. CONCLUSION: This study unveils a WI/R response gene set that will help to explore molecular pathways involved in the tissue damage after WI/R. In addition, these genes especially Hsp70 and Gadd45a might represent promising new candidates indicating WI/R liver damage.
基金supported by the Natural Science Foundation of Jiangxi Province(Nos.20212BAB214005 and 20212ACB214002)the Research startup fund of East China Jiaotong University(No.465).
文摘Optical imaging possesses important implications for early disease diagnosis,timely disease treatment,and basic medical as well as biological research.Compared with the traditionary near-infrared(NIR-I)window(650-950 nm)optical imaging,the emerging second near-infrared(NIR-II)window optical imaging technology owns the great superiorities of non-invasiveness,nonionizing radiation,and real-time dynamic imaging with the low biological interference,can significantly improve the tissue penetration depth and detection sensitivity,thus expecting to achieve accurate and precise diagnosis of major diseases.Inspired by the conspicuous superiorities,an increasing number of versatile NIR-II fluorophores have been legitimately designed and engineered for precisely deep-tissue mapping-mediated theranostics of life-threatening diseases.Organic semiconducting nanomaterials(OSNs)are derived from organic conjugated molecules withπ-electron delocalized skeletons,which show greatly preponderant prospects in the biomedicine field due to the excellent photoelectric property,tunable energy bands,and fine biocompatibility.In this review,the superiorities of NIR-II fluorescence imaging using OSNs for brilliant visualization various of diseases,including tongue cancer,ovarian cancer,osteosarcoma,bacteria or pathogens infection,kidney dysfunction,rheumatoid arthritis,liver injury,and cerebrovascular function,are emphatically summarized.Finally,the reasonable prospects and persistent efforts for repurposing OSNs to facilitate the clinical translation of NIR-II fluorescence phototheranostics are outlined.
文摘Background Apurinic apyrimidinic endonuclease/redox effector factor 1 （APE1/Ref-1） is an important enzyme in the repair of reactive oxygen species-induced DNA damage, and its expression/activation can be induced by reactive oxygen species. The aim of this research was to investigate the relationship between multiple-organ injuries and expression of Ref-1 in the early period after liver transplantation. Methods One hundred and fifty adult male Wistar rats were divided randomly into three groups： liver transplantation, sham surgery, and untreated control. After liver transplantation, animals were sacrificed at different time points. Hepatic and renal functions were analyzed by serology. Histology, apoptotic levels, and Ref-1 expression were examined by immunohistochemistry in the liver, kidneys, intestines, and lungs. Results Serum levels of alanine aminotransferase and aspartate aminotransferase peaked 6 hours after liver transplantation and decreased appreciably after 12 hours in the transplantatior~ group, suggesting that the degree of liver injury in the early period after transplantation peaked at 6 hours and then decreased. Pathological analyses showed that hepatic tissues were more severely injured in the transplantation group than in the sham and untreated groups. A considerable number of infiltrating inflammatory cells was observed around the portal vein in the transplantation group. Injuries to the kidneys, intestines, and lungs were milder after liver transplantation. Apoptotic levels increased after liver transplantation in all four organs examined. Ref-1 expression was higher in the transplantation group in the early period after liver transplantation than in the sham surgery and untreated control groups. Conclusion Ref-1 expression induced by ischemia-reperfusion injury may have a critical role in repairing multiple-organ injuries after liver transplantation.
基金Natural Science Foundation ofChina(Nos.81974552,81774160)the Scientific Research Foundation of the Science and Technology Department of Sichuan Province(No.2022YFS0417).
文摘Severe acute pancreatitis(SAP)is a life-threatening acute abdominal disease with two peaks of death:the first in the early stage,characterized by systemic inflammatory response-associated organ failure;and the second in the late stage,characterized by infectious complications.Neutrophils are the main immune cells participating in the whole process of SAP.In addition to the traditional recognition of neutrophils as the origination of chemokine and cytokine cascades or phagocytosis and degranulation of pathogens,neutrophil extracellular traps(NETs)also play an important roles in inflammatory reactions.We reviewed the role of NETs in the occurrence and development of SAP and its fatal complications,including multiple organs injury,infected pancreatic necrosis,and thrombosis.This review provides novel insights into the involvement of NETs throughout the entire process of SAP,showing that targeting NETs might be a promising strategy in SAP treatment.However,precision therapeutic options targeting NETs in different situations require further investigation.
文摘The kidneys have a close functional relationship with other organs especially the lungs. This connection makes the kidney and the lungs as the most organs involved in the multi-organ failure syndrome. The combination of acute lung injury （ALl） and renal failure results a great clinical significance of 80% mortality rate. Acute kidney injury （AKI） leads to an increase in circulating cytokines, chemokines, activated innate immune cells and diffuse of these agents to other organs such as the lungs. These factors initiate pathological cascade that ultimately leads to ALl and acute respiratory distress syndrome （ARDS）. We comprehensively searched the English medical literature focusing on AKI, ALl, organs cross talk, renal failure, multi organ failure and ARDS using the databases of PubMed, Embase, Scopus and directory of open access journals. In this narrative review, we summarized the pathophysiology and treatment of respiratory distress syndrome following AKI. This review promotes knowledge of the link between kidney and lung with mechanisms, diagnostic biomarkers, and treatment involved ARDS induced by AKI.
