Neuron-astrocyte interactions are vital for the brain’s connectome.Understanding astrocyte activities is crucial for comprehending the complex neural network,particularly the population-level functions of neurons in ...Neuron-astrocyte interactions are vital for the brain’s connectome.Understanding astrocyte activities is crucial for comprehending the complex neural network,particularly the population-level functions of neurons in different cortical states and associated behaviors in mammals.Studies on animal sleep and wakefulness have revealed distinct cortical synchrony patterns between neurons.Astrocytes,outnumbering neurons by nearly fivefold,support and regulate neuronal and synaptic function.Recent research on astrocyte activation during cortical state transitions has emphasized the influence of norepinephrine as a neurotransmitter and calcium waves as key components of ion channel signaling.This summary focuses on a few recent studies investigating astrocyte-neuron interactions in mouse models during sleep,wakefulness,and arousal levels,exploring the involvement of noradrenaline signaling,ion channels,and glutamatergic signaling in different cortical states.These findings highlight the significant impact of astrocytes on large-scale neuronal networks,influencing brain activity and responsiveness.Targeting astrocytic signaling pathways shows promise for treating sleep disorders and arousal dysregulation.More research is needed to understand astrocytic calcium signaling in different brain regions and its implications for dysregulated brain states,requiring future human studies to comprehensively investigate neuron-astrocyte interactions and pave the way for therapeutic interventions in sleep-and arousal-related disorders.展开更多
Objective:Myocardial ischemia-reperfusion injury(MIRI)is one of the leading causes of death from cardiovascular disease in humans,especially in individuals exposed to cold environments.Long non-coding RNAs(lncRNAs)reg...Objective:Myocardial ischemia-reperfusion injury(MIRI)is one of the leading causes of death from cardiovascular disease in humans,especially in individuals exposed to cold environments.Long non-coding RNAs(lncRNAs)regulate MIRI through multiple mechanisms.This study explored the regulatory effect of lncRNA-AK138945 on myocardial ischemia-reperfusion injury and its mechanism.Methods:In vivo,8-to 12-weeks-old C57BL/6 male mice underwent ligation of the left anterior descending coronary artery for 50 minutes followed by reperfusion for 48 hours.In vitro,the primary cultured neonatal mouse ventricular cardiomyocytes(NMVCs)were treated with 100μmol/L hydrogen peroxide(H_(2)O_(2)).The knockdown of lncRNA-AK138945 was evaluated to detect cardiomyocyte apoptosis,and a glucose-regulated,endoplasmic reticulum stress-related protein 94(GRP94)inhibitor was used to detect myocardial injury.Results:We found that the expression level of lncRNA-AK138945 was reduced in MIRI mouse heart tissue and H2O2-treated cardiomyocytes.Moreover,the proportion of apoptosis in cardiomyocytes increased after lncRNA-AK138945 was silenced.The expression level of Bcl2 protein was decreased,and the expression level of Bad,Caspase 9 and Caspase 3 protein was increased.Our further study found that miR-1a-3p is a direct target of lncRNA-AK138945,after lncRNA-AK138945 was silenced in cardiomyocytes,the expression level of miR-1a-3p was increased while the expression level of its downstream protein GRP94 was decreased.Interestingly,treatment with a GRP94 inhibitor(PU-WS13)intensified H2O2-induced cardiomyocyte apoptosis.After overexpression of FOXO3,the expression levels of lncRNA-AK138945 and GRP94 were increased,while the expression levels of miR-1a-3p were decreased.Conclusion:LncRNA-AK138945 inhibits GRP94 expression by regulating miR-1a-3p,leading to cardiomyocyte apoptosis.The transcription factor Forkhead Box Protein O3(FOXO3)participates in cardiomyocyte apoptosis induced by endoplasmic reticulum stress through up-regulation of lncRNA-AK138945.展开更多
Objective:To evaluate the combination therapy of pyronaridine tetraphosphate and diminazene aceturate against Babesia in vitro and in vivo.Methods:Bioinformatic analysis was performed using atom pair fingerprints.An i...Objective:To evaluate the combination therapy of pyronaridine tetraphosphate and diminazene aceturate against Babesia in vitro and in vivo.Methods:Bioinformatic analysis was performed using atom pair fingerprints.An in vitro combination test was performed against Babesia bovis and Theileria equi.Moreover,the in vivo chemotherapeutic efficacy of pyronaridine tetraphosphate in combination with diminazene aceturate was investigated against the growth of Babesia microti in mice using a fluorescence inhibitory assay.Results:Pyronaridine tetraphosphate and diminazene aceturate exhibited nearly similar molecular weights.The in vitro combination of pyronaridine tetraphosphate and diminazene aceturate was synergistic on Babesia bovis and additive on Theileria equi.In addition,5 mg/kg pyronaridine tetraphosphate combined with 10 mg/kg diminazene aceturate inhibited Babesia microti growth significantly compared with those observed after treatment with 25 mg/kg diminazene aceturate alone from day 6 post treatment to day 12 post treatment.The combination therapy also normalized the hematological parameters of infected mice.Conclusions:An oral dose of pyronaridine tetraphosphate combined with a subcutaneous dose of diminazene aceturate inhibits Babesia in vitro and in mice,suggesting it might be a new paradigm for the treatment of babesiosis.展开更多
Fexofenadine is useful in various allergic disease treatment.However,the pharmacokinetic variability information and quantitative factor identification of fexofenadine are very lacking.This study aimed to verify the v...Fexofenadine is useful in various allergic disease treatment.However,the pharmacokinetic variability information and quantitative factor identification of fexofenadine are very lacking.This study aimed to verify the validity of previously proposed genetic factors through fexofenadine population pharmacokinetic modeling and to explore the quantitative correlations affecting the pharmacokinetic variability.Polymorphisms of the organic-anion-transporting-polypeptide(OATP)1B1 and 2B1 have been proposed to be closely related to fexofenadine pharmacokinetic diversity.Therefore,modeling was performed using fexofenadine oral exposure data according to the OATP1B1-and 2B1-polymorphisms.OATP1B1 and 2B1 were identified as effective covariates of clearance(CL/F)and distribution volume(V/F)-CL/F,respectively,in fexofenadine pharmacokinetic variability.CL/F and average steady-state plasma concentration of fexofenadine differed by up to 2.17-and 2.20-folds,respectively,depending on the OATP1B1 polymorphism.Among the individuals with different OATP2B1 polymorphisms,the CL/F and V/F differed by up to 1.73-and 2.00-folds,respectively.Ratio of the areas under the curves following single-and multiple-administrations,and the cumulative ratio were significantly different between OATP1B1-and 2B1-polymorphism groups.Based on quantitative prediction comparison through a model-based approach,OATP1B1 was confirmed to be relatively more important than 2B1 regarding the degree of effect on fexofenadine pharmacokinetic variability.Based on the established pharmacokineticpharmacodynamic relationship,the difference in fexofenadine efficacy according to genetic polymorphisms of OATP1B1 and 2B1 was 1.25-and 0.87-times,respectively,and genetic consideration of OATP1B1 was expected to be important in the pharmacodynamics area as well.This population pharmacometrics study will be a very useful starting point for fexofenadine precision medicine.展开更多
Although solar exposure is necessary for human health,phototoxicology induced by excessive UVB and UVA radiation,which involves sunburns,skin aging and even tu-morigenesis,has been widely researched.Sunscreen is one o...Although solar exposure is necessary for human health,phototoxicology induced by excessive UVB and UVA radiation,which involves sunburns,skin aging and even tu-morigenesis,has been widely researched.Sunscreen is one of the most important ways to protect skin from UV phototoxic damage.As well as inorganic and organic UV filters,some natural products or plant extracts with aromatic rings in their structures,such as flavonoids or polyphenols,can absorb UV to reduce sunburn,acting as a natu-ral UV filter;they also show antioxidant or/and anti-inflammatory activity.This could explain why,although there are no officially approval natural commercial sun-filters,more and more commercial sunscreen products containing plant extracts are avail-able on the market.Here we summarize articles focusing on natural UV filters from plant published in the last 6 years,selecting the most significant data in order to better understand the photoprotective activity of natural products and extracts from plants,including their major constituents and main biological effects,methods for evaluating UV radiation resistance,anti-UV radiation experimental models and anti-UV radiation mechanisms.展开更多
Metabolic associated fatty liver disorder(MAFLD)characterizes the contributing etiologies(i.e.,type 2 diabetes mellitus,metabolic syndrome,overweight)of individuals with fatty liver disease that affects 1/3rd of the w...Metabolic associated fatty liver disorder(MAFLD)characterizes the contributing etiologies(i.e.,type 2 diabetes mellitus,metabolic syndrome,overweight)of individuals with fatty liver disease that affects 1/3rd of the world population.In 2020,the coronavirus disease 2019(COVID-19)crisis was unprecedented,and people with different comorbidities became more susceptible to the infection caused by severe acute respiratory syndrome coronavirus 2.MAFLD patients are frequently obese with added metabolic menace like diabetes,hypertension,and dyslipidemia leading to greater jeopardy of COVID-19.MAFLD patients are 4 to 6-fold more prone towards infections.COVID-19 induces liver injury with elevated levels of aspartate aminotransferase and alanine aminotransferase and insignificantly elevated bilirubin.Hence,MAFLD in COVID-19 patients worsens the condition significantly.The evidence highlighting the interaction between MAFLD and altered liver functioning in COVID-19 suggested that COVID-19 patients with pre-existing MAFLD are at greater risk of morbidity or intensive care unit admission.Direct hepatic injury,enhanced levels of inflammatory cytokines,declined hepatic mitochondrial activity,and compromised immunity are considered as some underlying mechanisms.The main focus of this review is to discuss the implications of metabolic dysfunction associated with fatty liver disease in COVID-19 patients.The review systematically analyzes the effect of striking two worldwide pandemics(MAFLD and COVID-19)together in the present era.展开更多
Objective:This work aimed to report the first complete mitochondrial genome(mitogenome)of Rheum palmatum,summarize the features of Caryophyllales mitogenomes,and to reveal the potential of utilizing the mitogenomes of...Objective:This work aimed to report the first complete mitochondrial genome(mitogenome)of Rheum palmatum,summarize the features of Caryophyllales mitogenomes,and to reveal the potential of utilizing the mitogenomes of R.palmatum and other Caryophyllales species for inferring phylogenetic relationships and species identification.Methods:Both Illumina short reads and PacBio HiFi reads were utilized to obtain a complete mitogenome of R.palmatum.A variety of bioinformatics tools were employed to characterize the R.palmatum mitogenome,compare the reported mitogenomes in Caryophyllales and conduct phylogenetic analysis.Results:The mitogenome of R.palmatum was assembled into a single master circle of 302,993 bp,encoding 35 known protein-coding genes,18 transfer RNA genes,and three ribosome RNA genes.A total of 249 long repeats and 49 simple sequence repeats were identified in this mitogenome.The sizes of mitogenomes in Caryophyllales varied from 253 kb to 11.3 Mb.Among them,23 mitogenomes were circular molecules,one was linear,and one consisted of relaxed circles,linear molecules,and supercoiled DNA.Out of the total mitogenomes,11 were single-chromosome structure,whereas the remaining 14 were multi-chromosomal organizations.The phylogenetic analysis is consistent with both the Engler system(1964)and the Angiosperm Phylogeny Group III system.Conclusions:We obtained the first mitogenome of R.palmatum,which consists of a master circle.Mitogenomes in Caryophyllales have variable genome sizes and structures even within the same species.Circular molecules are still the dominant pattern in Caryophyllales.Single-chromosome mitogenomes account for nearly a half of all the mitogenomes in Caryophyllales,in contrast to previous studies.It is feasible to utilize mitochondrial genomes for inferring phylogenetic relationships and conducting species identification.展开更多
BACKGROUND Depression is one of the most common and important psychological issues faced by dialysis patients.It can make it more difficult for them to adhere to their treatment regimen,which,in turn,can worsen their ...BACKGROUND Depression is one of the most common and important psychological issues faced by dialysis patients.It can make it more difficult for them to adhere to their treatment regimen,which,in turn,can worsen their physical symptoms and lead to poorer health outcomes.AIM To examine the evolution and growth of publications related to dialysis and depression.The objectives were to identify the number of publications,the top active countries,the contributed institutions,funding agencies and journals,as well as to perform citation and research theme analysis.METHODS The search was conducted using the Scopus database for publications related to dialysis and depression between 1970 and 2022.Subsequently,bibliometric analysis was carried out on the data obtained using VOSviewer software,version 1.6.9.This analysis included visualization analysis,co-occurrence analysis and examination of publication trends in dialysis and depression.RESULTS We identified 800 publications that met the search criteria.The number of publications related to dialysis and depression has increased significantly in the past two decades.The USA led the way with 144 publications,which is 18%of all publications on this topic.Turkey came second with 88 publications(11%),followed by China with 55 publications(6.88%)and Iran with 52 publications(6.5%).Analysis of the research theme identified three main clusters related to gender differences in prevalence,identification of depression as a risk factor,and effective interventions to relieve depression.Future research direction analysis shows a shift toward effective interventions to relieve depression in dialysis patients.CONCLUSION This study provides a comprehensive overview of growth,trends and research themes related to dialysis and depression that could help researchers identify gaps in the literature and develop future research.展开更多
BACKGROUND The global spread of severe acute respiratory syndrome coronavirus 2,responsible for coronavirus disease 2019(COVID-19),poses a significant risk to public health.Beyond the respiratory issues initially asso...BACKGROUND The global spread of severe acute respiratory syndrome coronavirus 2,responsible for coronavirus disease 2019(COVID-19),poses a significant risk to public health.Beyond the respiratory issues initially associated with the condition,severe cases of COVID-19 can also lead to complications in other organs,including the liver.Patients with severe COVID-19 may exhibit various clinical signs of liver dysfunction,ranging from minor elevations in liver enzymes without symptoms to more serious cases of impaired liver function.Liver damage is more commonly observed in patients with severe or critical forms of the disease.AIM To present the research landscape on COVID-19 and liver dysfunction while also offering valuable insights into the prominent areas of interest within this particular domain.METHODS On 18 February 2023,Scopus was utilised to conduct a comprehensive exploration of the relationship between COVID-19 and the liver dysfunction.The investigation encompassed the period from 1 January 2020 to 31 December 2022.Primary sources were meticulously examined and organised in a Microsoft Excel 2013 spreadsheet,categorised by journal,institution,funding agency,country and citation type.VOSviewer version 1.6.18 was employed to explore the prominent topics and knowledge network related to the subject.RESULTS There were 2336 publications on COVID-19 and liver dysfunction analysed in this study,of which 558 were published in 2020,891 in 2021 and 887 in 2022.Researchers from 111 different countries participated in the retrieved documents.The United States contributed the most studies,with 497 documents,representing 21.28%of the total,followed by China with 393 documents(16.82%)and Italy with 255 documents(10.92%).In the context of research related to COVID-19 and the liver,co-occurrence analysis identified three distinct clusters of topics:(1)‘COVID-19 vaccines in liver transplant recipients’;(2)‘liver function tests as a predictor of the severity and clinical outcomes in hospitalised patients’;and(3)‘care of patients with liver disease during the COVID-19 pandemic’.CONCLUSION This bibliometric study provides a comprehensive overview of liver-related publications in COVID-19 research over the past 3 years.This study highlights the significant contributions of high-income nations,particularly the United States,China,and Italy,to the production of liver-related scholarly literature in this field.Most of the articles focused on liver dysfunction in patients with COVID-19 and the implications of the virus for gastroenterologists and hepatologists.展开更多
Objective:To assess the effectiveness and adverse drug reactions of all-oral regimens for patients with multidrug-resistant tuberculosis.Methods:This retrospective study was conducted at 10 Programmatic Management of ...Objective:To assess the effectiveness and adverse drug reactions of all-oral regimens for patients with multidrug-resistant tuberculosis.Methods:This retrospective study was conducted at 10 Programmatic Management of Drug Resistant Tuberculosis sites in Punjab province of Pakistan.Patients receiving treatment for drug resistant tuberculosis from July 2019 to December 2020 with at least interim result i.e.6th month culture conversion or final outcomes(cured,complete,lost to follow-up,failure,death)available,were included in the study.Data was extracted from electronic data management system.For the reporting and management of adverse drug events,active tuberculosis drug safety monitoring and management was implemented across all sites.All the data was analyzed using SPSS version 22.Results:Out of 947 drug resistant tuberculosis patients included in this study,579(68%)of the patients had final outcomes available.Of these,384(67.9%)successfully completed their treatment.Out of 368(32%)patients who had their interim results available,all had their 6th month culture negative.Combining new medications was thought to result in serious adverse outcomes such as QT prolongation.However,this study did not record any severe adverse events among patients.Conclusions:All-oral regimens formulation guided by overall treatment effectiveness resulted in treatment outcomes comparable to those obtained with traditional injectable treatment.展开更多
BACKGROUND Crohn’s disease represents a challenge for patients concerned with the modified diet regimen as well as practitioners who seek the best nutritional therapy.Crohn’s disease can alter the body’s ability to...BACKGROUND Crohn’s disease represents a challenge for patients concerned with the modified diet regimen as well as practitioners who seek the best nutritional therapy.Crohn’s disease can alter the body’s ability to digest food and to absorb nutrients,resulting in severe vitamin deficiencies,malnutrition and sometimes lifethreatening complications.However,a comprehensive bibliometric analysis is lacking to map the current links between nutrition and Crohn’s disease in terms of the number of citations,geographic distribution and growth trends of publications.AIM To introduce the current state of research as well as hotspots in the field of nutrition and Crohn’s disease from a bibliometric standpoint.METHODS We searched the Scopus database and selected the relevant literature on nutrition and Crohn’s disease that met the inclusion criteria.We analyzed the publication trends and research hotspots by using video object segmentation viewer software.RESULTS We included 1237 publications.The number of documents published each year has increased steadily.The United States and the University of Otago,Christchurch,have had the highest productivity,with 208(16.81%)and 29(2.34%)documents,respectively.The“role of exclusive enteral nutrition for complicated Crohn’s disease”and“manipulation of the gut microbiota as a key target for Crohn’s disease”were the major research areas in 2016-2021,and they could be extensively investigated in the future.Meanwhile,research on“malnutrition in patients with Crohn’s disease”appeared to be an area that attracted more research attention before 2016.CONCLUSION This is the first bibliometric analysis to map the knowledge structure and trends regarding nutrition in Crohn’s disease research over the past two decades.The results provide a comprehensive summary and identification of the frontiers of nutrition and Crohn’s disease-related research,which may be used as a resource by researchers in the field.展开更多
Objective:To predict and analyze the potential Q-markers of Chuanxiong Chatiao Prescription,and the pharmacokinetic properties of pulvis and pills in vivo were studied,which provided a basis for the rational evaluatio...Objective:To predict and analyze the potential Q-markers of Chuanxiong Chatiao Prescription,and the pharmacokinetic properties of pulvis and pills in vivo were studied,which provided a basis for the rational evaluation of the phenomenon of“Different Dosage Forms of the Same Prescription”.Methods and Material:Q-markers analysis of Chuanxiong Chatiao Prescription based on the“Five Principles”(traceability and transmissibility,specificity,effectiveness,prescription compatibility and testability).The content determination method of Q-markers in Chuanxiong Chatiao Prescription was established by UPLC,and the content difference of Q-markers in the two dosage forms ware determined and compared.The Q-markers in rabbit plasma was determined by LC-MS/MS method,and the pharmacokinetic parameters of Q-markers in pulvis and pills were analyzed.Results:A total of 16 potential Q-markers from the“Five Principles”were used,nine components of tetramethylprazine,ferulic acid,glycyrrhizin,glycyrrhizic acid,luteolin,cimicifugoside,senkyunolideⅠ,isoimperatorin,nodakenin were identified as Q-markers of Chuanxiong Chatiao Presciption.The content of tetramethylprazine and other components in the pulvis form was found to be significantly higher than that in the pills,while the content of senkyunolideⅠwas lower than that in the pills,which may be related to the preparation process of the dosage form and the physicochemical properties of the components.Compared with pulvis,the Tmax and t_(1/2)of ferulic acid and other components in pills were significantly prolonged.To a certain extent,it can explain the classical theory of traditional Chinese medicine“Components in pulvis release quickly and take effect in fast-acting manner,while in pills release slowly and take effect in slow-acting”.Meanwhile,the Cmax and AUC0-t of tetramethylprazine and other components in pills were higher than those in pulvis,which showed unexpected pharmacokinetic characteristics,indicating the complexity of compounding and the importance of dosage form design.Conclusions:A method for the determination of Q-markers content was established by UPLC,which provide reference for the quality control of Chuanxiong Chatiao Prescription.In vivo studies have found the pharmacokinetic parameters indicate the absorption and distribution characteristics of pulvis and pills.However,it is also found that the release behavior of different components not only affected by the dosage form but also closely related to their own physical and chemical properties.展开更多
BACKGROUND The gut microbiota plays a crucial role in gastrointestinal and overall health.Randomized clinical trials(RCTs)play a crucial role in advancing our knowledge and evaluating the efficacy of therapeutic inter...BACKGROUND The gut microbiota plays a crucial role in gastrointestinal and overall health.Randomized clinical trials(RCTs)play a crucial role in advancing our knowledge and evaluating the efficacy of therapeutic interventions targeting the gut microbiota.AIM To conduct a comprehensive bibliometric analysis of the literature on RCTs involving the gut microbiota.METHODS Using bibliometric tools,a descriptive cross-sectional investigation was conducted on scholarly publications concentrated on RCTs related to gut microbiota,spanning the years 2003 to 2022.The study used VOSviewer version 1.6.9 to examine collaboration networks between different countries and evaluate the frequently employed terms in the titles and abstracts of the retrieved publications.The primary objective of this analysis was to identify key research areas and focal points associated with RCTs involving the gut microbiota.RESULTS A total of 1061 relevant articles were identified from the 24758 research articles published between 2003 and 2022.The number of publications showed a notable increase over time,with a positive correlation(R2=0.978,P<0.001).China(n=276,26.01%),the United States(n=254,23.94%),and the United Kingdom(n=97,9.14%)were the leading contributing countries.Københavns Universitet(n=38,3.58%)and Dankook University(n=35,3.30%)were the top active institutions.The co-occurrence analysis shows current gut microbiota research trends and important topics,such as obesity interventions targeting the gut microbiota,the efficacy and safety of fecal microbiota transplantation,and the effects of dietary interventions on humans.CONCLUSION The study highlights the rapid growth and importance of research on RCTs that involve the gut microbiota.This study provides valuable insight into research trends,identifies key players,and outlines potential future directions in this field.Additionally,the co-occurrence analysis identified important topics that play a critical role in the advancement of science and provided insights into future research directions in this field.展开更多
For the purpose of solving the engineering constrained discrete optimization problem, a novel discrete particle swarm optimization(DPSO) is proposed. The proposed novel DPSO is based on the idea of normal particle swa...For the purpose of solving the engineering constrained discrete optimization problem, a novel discrete particle swarm optimization(DPSO) is proposed. The proposed novel DPSO is based on the idea of normal particle swarm optimization(PSO), but deals with the variables as discrete type, the discrete optimum solution is found through updating the location of discrete variable. To avoid long calculation time and improve the efficiency of algorithm, scheme of constraint level and huge value penalty are proposed to deal with the constraints, the stratagem of reproducing the new particles and best keeping model of particle are employed to increase the diversity of particles. The validity of the proposed DPSO is examined by benchmark numerical examples, the results show that the novel DPSO has great advantages over current algorithm. The optimum designs of the 100?1 500 mm bellows under 0.25 MPa are fulfilled by DPSO. Comparing the optimization results with the bellows in-service, optimization results by discrete penalty particle swarm optimization(DPPSO) and theory solution, the comparison result shows that the global discrete optima of bellows are obtained by proposed DPSO, and confirms that the proposed novel DPSO and schemes can be used to solve the engineering constrained discrete problem successfully.展开更多
AIM To determine the short-term biochemical effects and clinical tolerability of intermittent fasting(IF) in adults with type 2 diabetes mellitus(T2DM).METHODS We describe a three-phase observational study(baseline 2 ...AIM To determine the short-term biochemical effects and clinical tolerability of intermittent fasting(IF) in adults with type 2 diabetes mellitus(T2DM).METHODS We describe a three-phase observational study(baseline 2 wk, intervention 2 wk, follow-up 2 wk) designed to determine the clinical, biochemical, and tolerability of IF in community-dwelling volunteer adults with T2DM. Biochemical, anthropometric, and physical activity measurements(using the Yale Physical Activity Survey) were taken at the end of each phase. Participants reported morning, afternoon and evening self-monitored blood glucose(SMBG) and fasting duration on a daily basis throughout all study stages, in addition to completing a remote food photography diary three times within each study phase. Fasting blood samples were collected on the final days of each study phase. RESULTS At baseline, the ten participants had a confirmed diagnosis of T2DM and were all taking metformin, and on average were obese [mean body mass index(BMI) 36.90 kg/m^2]. We report here that a short-term periodof IF in a small group of individuals with T2DM led to significant group decreases in weight(-1.395 kg, P = 0.009), BMI(-0.517, P = 0.013), and at-target morning glucose(SMBG). Although not a study requirement, all participants preferentially chose eating hours starting in the midafternoon. There was a significant increase(P < 0.001) in daily hours fasted in the IF phase(+5.22 h), although few attained the 18-20 h fasting goal(mean 16.82 ± 1.18). The increased fasting duration improved at-goal(< 7.0 mmol/L) morning SMBG to 34.1%, from a baseline of 13.8%. Ordinal Logistic Regression models revealed a positive relationship between the increase in hours fasted and fasting glucose reaching target values(χ~2 likelihood ratio = 8.36, P = 0.004) but not for afternoon or evening SMBG(all P > 0.1). Postprandial SMBGs were also improved during the IF phase, with 60.5% readings below 9.05 mmol/L, compared to 52.6% at baseline, and with less glucose variation. Neither insulin resistance(HOMAIR), nor inflammatory markers(C-reactive protein) normalized during the IF phase. IF led to an overall spontaneous decrease in caloric intake as measured by food photography(Remote Food Photography Method). The data demonstrated discernable trends during IF for lower energy, carbohydrate, and fat intake when compared to baseline. Physical activity, collected by a standardized measurement tool(Yale Physical Activity Survey), increased during the intervention phase and subsequently decreased in the follow-up phase. IF was well tolerated in the majority of individuals with 6/10 participants stating they would continue with the IF regimen after the completion of the study, in a full or modified capacity(i.e., every other day or reduced fasting hours).CONCLUSION The results from this pilot study indicate that shortterm daily IF may be a safe, tolerable, dietary intervention in T2DM patients that may improve key outcomes including body weight, fasting glucose and postprandial variability. These findings should be viewed as exploratory, and a larger, longer study is necessary to corroborate these findings.展开更多
This study investigated the effects and molecular mechanisms of genistein in improving insulin resistance induced by free fatty acids (FFAs) in HepG2 hepatocytes. A model of insulin resistance in HepG2 cells was estab...This study investigated the effects and molecular mechanisms of genistein in improving insulin resistance induced by free fatty acids (FFAs) in HepG2 hepatocytes. A model of insulin resistance in HepG2 cells was established by adding palmitic acid (0.5 mmol/L) to the culture medium and the cells were treated by genistein. Glucose consumption of HepG2 cells was determined by glucose oxidase method. The levels of c-jun N-terminal kinase (JNK) phosphorylation, insulin receptor substrate-1 (IRS-1) Ser307 phosphorylation, JNK, IRS-1, phosphatidylinositol-3-kinase p85 (PI-3K p85) and glucose transporter 1 (GLUT1) proteins were detected by Western blotting. The results showed that after the treatment with palmitic acid for 24 h, the insulin-stimulated glucose transport in HepG2 cells was inhibited, and the glucose consumption was substantially reduced. Meanwhile, the expressions of IRS-1, PI-3K p85 protein and GLUT1 were obviously reduced, while the levels of JNK phosphorylation and IRS-1 Ser307 phosphorylation and the expression of JNK protein were significantly increased, as compared with cells of normal control. However, the aforementioned indices, which indicated the existence of insulin resistance, were reversed by genistein at 1-4 μmol/L in a dose-dependent manner. It was concluded that insulin resistance induced by FFAs in HepG2 hepatocytes could be improved by genistein. Genistein might reverse FFAs-induced insulin resistance in HepG2 cells by targeting JNK.展开更多
AIM To investigate whether morin can reduce hepatic fibrosis by activating the NF-E2-related factor 2(Nrf2) signaling pathway.METHODS Twenty male Sprague-Dawley rats were randomly divided into four groups: control gro...AIM To investigate whether morin can reduce hepatic fibrosis by activating the NF-E2-related factor 2(Nrf2) signaling pathway.METHODS Twenty male Sprague-Dawley rats were randomly divided into four groups: control group, morin group, carbon tetrachloride(CCl4) group, and morin + CCl4 group. Rats in both the CCl4 and morin + CCl4 groups were injected intraperitoneally with CCl4 at a dose of 2 mL/kg twice a week. Rats in both the morin and morin + CCl4 groups were treated orally with morin at a dose of 50 mg/kg twice a week. Control rats were treated with vehicle only twice a week. At the end-point of the 8 wk of the experimental period, serum AST, ALT, and ALP were measured, and the liver specimenswere obtained for pathological assessment. Real-time PCR and Western blot methods were used to analyze the expression of α-smooth muscle actin(α-SMA), collagen Ⅰ, collagen Ⅲ, Nrf2, heme oxygenase(HO-1), and quinone oxidoreductase 1(NQO1) using frozen liver specimens.RESULTS Morin-treated rats in the morin + CCl4 group had less hyperplasia of fiber tissue, minimal inflammatory cells, and less body weight loss with favorable liver enzyme measurements compared to rats treated with CCl4 only. Additionally, morin-treated rats had significantly lower m RNA and protein expression of α-SMA, collagen Ⅰ, and collagen Ⅲ, but significantly higher m RNA and protein expression of Nrf2, HO-1, and NQO1 compared to rats treated with CCl4 only(P < 0.05).CONCLUSION Morin could play a protective role by inducing the expression of Nrf2 and its downstream antioxidant factors(HO-1 and NQO1) and reducing the expression of α-SMA, collagen Ⅰ, and collagen Ⅲ in CCl4-induced liver fibrosis rats.展开更多
AIM To investigate the dynamic alteration of mitochondrial carnitine palmitoyl transferase Ⅱ(CPT-Ⅱ) expression during malignant transformation of rat hepatocytes.METHODS Sprague-Dawley male rats were fed with normal...AIM To investigate the dynamic alteration of mitochondrial carnitine palmitoyl transferase Ⅱ(CPT-Ⅱ) expression during malignant transformation of rat hepatocytes.METHODS Sprague-Dawley male rats were fed with normal, high fat(HF), and HF containing 2-fluorenylacetamide(2-FAA) diet, respectively. According to the Hematoxylin and Eosin staining of livers, rats were divided into control, fatty liver, degeneration, pre-cancerous, and cancerous groups. Liver lipids were dyed with Oil Red O, CPT-Ⅱ alterations were analyzed by immunohistochemistry, and compared with CPT-Ⅱ specific concentration(μg/mg protein). Levels of total cholesterol(Tch), triglyceride(TG), and aminotransferases [alanine aminotransferase(ALT), aspartate aminotransferase(AST)] were determined by the routine methods.RESULTS After intake of HF and/or HF+2-FAA diets, the rat livers showed mass lipid accumulation. The lipid level in the control group was significantly lower than that in other groups. The changes of serum TG and Tch levels were abnormally increasing, 2-3 times more than those in the controls(P < 0.05). During the rat liver morphological changes from normal to cancer development process with hepatocyte injury, serum AST and ALT levels were significantly higher(4-8 times, P < 0.05) than those in the control group. The specific concentration of CPT-Ⅱ in liver tissues progressively decreased during hepatocyte malignant transformation, with the lowest CPT-Ⅱ levels in the cancer group than in any of the other groups(P < 0.05).CONCLUSION Low CPT-Ⅱ expression might lead to abnormal hepatic lipid accumulation, which should promote the malignant transformation of hepatocytes.展开更多
基金supported by the Corbett Estate Fund(62285-531021-41800,to EW)the Helen Vosburg McCrillus Plummer and Robert Edward Lee Plummer,Jr.Chair Fund(to JHH).
文摘Neuron-astrocyte interactions are vital for the brain’s connectome.Understanding astrocyte activities is crucial for comprehending the complex neural network,particularly the population-level functions of neurons in different cortical states and associated behaviors in mammals.Studies on animal sleep and wakefulness have revealed distinct cortical synchrony patterns between neurons.Astrocytes,outnumbering neurons by nearly fivefold,support and regulate neuronal and synaptic function.Recent research on astrocyte activation during cortical state transitions has emphasized the influence of norepinephrine as a neurotransmitter and calcium waves as key components of ion channel signaling.This summary focuses on a few recent studies investigating astrocyte-neuron interactions in mouse models during sleep,wakefulness,and arousal levels,exploring the involvement of noradrenaline signaling,ion channels,and glutamatergic signaling in different cortical states.These findings highlight the significant impact of astrocytes on large-scale neuronal networks,influencing brain activity and responsiveness.Targeting astrocytic signaling pathways shows promise for treating sleep disorders and arousal dysregulation.More research is needed to understand astrocytic calcium signaling in different brain regions and its implications for dysregulated brain states,requiring future human studies to comprehensively investigate neuron-astrocyte interactions and pave the way for therapeutic interventions in sleep-and arousal-related disorders.
基金This work was supported in part by the National Natural Science Foundation of China(82370417,81970320,82270273)the Certificate of China Postdoctoral Science Foundation Grant(2021M693826)+1 种基金the postdoctoral funding from Heilongjiang Province(21042230046)the Hai Yan Youth Fund from Harbin Medical University Cancer Hospital(JJQN2021-09).
文摘Objective:Myocardial ischemia-reperfusion injury(MIRI)is one of the leading causes of death from cardiovascular disease in humans,especially in individuals exposed to cold environments.Long non-coding RNAs(lncRNAs)regulate MIRI through multiple mechanisms.This study explored the regulatory effect of lncRNA-AK138945 on myocardial ischemia-reperfusion injury and its mechanism.Methods:In vivo,8-to 12-weeks-old C57BL/6 male mice underwent ligation of the left anterior descending coronary artery for 50 minutes followed by reperfusion for 48 hours.In vitro,the primary cultured neonatal mouse ventricular cardiomyocytes(NMVCs)were treated with 100μmol/L hydrogen peroxide(H_(2)O_(2)).The knockdown of lncRNA-AK138945 was evaluated to detect cardiomyocyte apoptosis,and a glucose-regulated,endoplasmic reticulum stress-related protein 94(GRP94)inhibitor was used to detect myocardial injury.Results:We found that the expression level of lncRNA-AK138945 was reduced in MIRI mouse heart tissue and H2O2-treated cardiomyocytes.Moreover,the proportion of apoptosis in cardiomyocytes increased after lncRNA-AK138945 was silenced.The expression level of Bcl2 protein was decreased,and the expression level of Bad,Caspase 9 and Caspase 3 protein was increased.Our further study found that miR-1a-3p is a direct target of lncRNA-AK138945,after lncRNA-AK138945 was silenced in cardiomyocytes,the expression level of miR-1a-3p was increased while the expression level of its downstream protein GRP94 was decreased.Interestingly,treatment with a GRP94 inhibitor(PU-WS13)intensified H2O2-induced cardiomyocyte apoptosis.After overexpression of FOXO3,the expression levels of lncRNA-AK138945 and GRP94 were increased,while the expression levels of miR-1a-3p were decreased.Conclusion:LncRNA-AK138945 inhibits GRP94 expression by regulating miR-1a-3p,leading to cardiomyocyte apoptosis.The transcription factor Forkhead Box Protein O3(FOXO3)participates in cardiomyocyte apoptosis induced by endoplasmic reticulum stress through up-regulation of lncRNA-AK138945.
基金supported by Deputyship for Research&Innovation,Ministry of Education in Saudi Arabia through the project number:ISP23-73.
文摘Objective:To evaluate the combination therapy of pyronaridine tetraphosphate and diminazene aceturate against Babesia in vitro and in vivo.Methods:Bioinformatic analysis was performed using atom pair fingerprints.An in vitro combination test was performed against Babesia bovis and Theileria equi.Moreover,the in vivo chemotherapeutic efficacy of pyronaridine tetraphosphate in combination with diminazene aceturate was investigated against the growth of Babesia microti in mice using a fluorescence inhibitory assay.Results:Pyronaridine tetraphosphate and diminazene aceturate exhibited nearly similar molecular weights.The in vitro combination of pyronaridine tetraphosphate and diminazene aceturate was synergistic on Babesia bovis and additive on Theileria equi.In addition,5 mg/kg pyronaridine tetraphosphate combined with 10 mg/kg diminazene aceturate inhibited Babesia microti growth significantly compared with those observed after treatment with 25 mg/kg diminazene aceturate alone from day 6 post treatment to day 12 post treatment.The combination therapy also normalized the hematological parameters of infected mice.Conclusions:An oral dose of pyronaridine tetraphosphate combined with a subcutaneous dose of diminazene aceturate inhibits Babesia in vitro and in mice,suggesting it might be a new paradigm for the treatment of babesiosis.
文摘Fexofenadine is useful in various allergic disease treatment.However,the pharmacokinetic variability information and quantitative factor identification of fexofenadine are very lacking.This study aimed to verify the validity of previously proposed genetic factors through fexofenadine population pharmacokinetic modeling and to explore the quantitative correlations affecting the pharmacokinetic variability.Polymorphisms of the organic-anion-transporting-polypeptide(OATP)1B1 and 2B1 have been proposed to be closely related to fexofenadine pharmacokinetic diversity.Therefore,modeling was performed using fexofenadine oral exposure data according to the OATP1B1-and 2B1-polymorphisms.OATP1B1 and 2B1 were identified as effective covariates of clearance(CL/F)and distribution volume(V/F)-CL/F,respectively,in fexofenadine pharmacokinetic variability.CL/F and average steady-state plasma concentration of fexofenadine differed by up to 2.17-and 2.20-folds,respectively,depending on the OATP1B1 polymorphism.Among the individuals with different OATP2B1 polymorphisms,the CL/F and V/F differed by up to 1.73-and 2.00-folds,respectively.Ratio of the areas under the curves following single-and multiple-administrations,and the cumulative ratio were significantly different between OATP1B1-and 2B1-polymorphism groups.Based on quantitative prediction comparison through a model-based approach,OATP1B1 was confirmed to be relatively more important than 2B1 regarding the degree of effect on fexofenadine pharmacokinetic variability.Based on the established pharmacokineticpharmacodynamic relationship,the difference in fexofenadine efficacy according to genetic polymorphisms of OATP1B1 and 2B1 was 1.25-and 0.87-times,respectively,and genetic consideration of OATP1B1 was expected to be important in the pharmacodynamics area as well.This population pharmacometrics study will be a very useful starting point for fexofenadine precision medicine.
基金supported by Henan Provincial Department of Education(No.21B350001)Zhengzhou science and technology department(No.ZZSZX202109 and ZZSZX202108).
文摘Although solar exposure is necessary for human health,phototoxicology induced by excessive UVB and UVA radiation,which involves sunburns,skin aging and even tu-morigenesis,has been widely researched.Sunscreen is one of the most important ways to protect skin from UV phototoxic damage.As well as inorganic and organic UV filters,some natural products or plant extracts with aromatic rings in their structures,such as flavonoids or polyphenols,can absorb UV to reduce sunburn,acting as a natu-ral UV filter;they also show antioxidant or/and anti-inflammatory activity.This could explain why,although there are no officially approval natural commercial sun-filters,more and more commercial sunscreen products containing plant extracts are avail-able on the market.Here we summarize articles focusing on natural UV filters from plant published in the last 6 years,selecting the most significant data in order to better understand the photoprotective activity of natural products and extracts from plants,including their major constituents and main biological effects,methods for evaluating UV radiation resistance,anti-UV radiation experimental models and anti-UV radiation mechanisms.
文摘Metabolic associated fatty liver disorder(MAFLD)characterizes the contributing etiologies(i.e.,type 2 diabetes mellitus,metabolic syndrome,overweight)of individuals with fatty liver disease that affects 1/3rd of the world population.In 2020,the coronavirus disease 2019(COVID-19)crisis was unprecedented,and people with different comorbidities became more susceptible to the infection caused by severe acute respiratory syndrome coronavirus 2.MAFLD patients are frequently obese with added metabolic menace like diabetes,hypertension,and dyslipidemia leading to greater jeopardy of COVID-19.MAFLD patients are 4 to 6-fold more prone towards infections.COVID-19 induces liver injury with elevated levels of aspartate aminotransferase and alanine aminotransferase and insignificantly elevated bilirubin.Hence,MAFLD in COVID-19 patients worsens the condition significantly.The evidence highlighting the interaction between MAFLD and altered liver functioning in COVID-19 suggested that COVID-19 patients with pre-existing MAFLD are at greater risk of morbidity or intensive care unit admission.Direct hepatic injury,enhanced levels of inflammatory cytokines,declined hepatic mitochondrial activity,and compromised immunity are considered as some underlying mechanisms.The main focus of this review is to discuss the implications of metabolic dysfunction associated with fatty liver disease in COVID-19 patients.The review systematically analyzes the effect of striking two worldwide pandemics(MAFLD and COVID-19)together in the present era.
基金financially supported by the National Natural Science Foundation of China (81874339)Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences (2022-I2M-1-018).
文摘Objective:This work aimed to report the first complete mitochondrial genome(mitogenome)of Rheum palmatum,summarize the features of Caryophyllales mitogenomes,and to reveal the potential of utilizing the mitogenomes of R.palmatum and other Caryophyllales species for inferring phylogenetic relationships and species identification.Methods:Both Illumina short reads and PacBio HiFi reads were utilized to obtain a complete mitogenome of R.palmatum.A variety of bioinformatics tools were employed to characterize the R.palmatum mitogenome,compare the reported mitogenomes in Caryophyllales and conduct phylogenetic analysis.Results:The mitogenome of R.palmatum was assembled into a single master circle of 302,993 bp,encoding 35 known protein-coding genes,18 transfer RNA genes,and three ribosome RNA genes.A total of 249 long repeats and 49 simple sequence repeats were identified in this mitogenome.The sizes of mitogenomes in Caryophyllales varied from 253 kb to 11.3 Mb.Among them,23 mitogenomes were circular molecules,one was linear,and one consisted of relaxed circles,linear molecules,and supercoiled DNA.Out of the total mitogenomes,11 were single-chromosome structure,whereas the remaining 14 were multi-chromosomal organizations.The phylogenetic analysis is consistent with both the Engler system(1964)and the Angiosperm Phylogeny Group III system.Conclusions:We obtained the first mitogenome of R.palmatum,which consists of a master circle.Mitogenomes in Caryophyllales have variable genome sizes and structures even within the same species.Circular molecules are still the dominant pattern in Caryophyllales.Single-chromosome mitogenomes account for nearly a half of all the mitogenomes in Caryophyllales,in contrast to previous studies.It is feasible to utilize mitochondrial genomes for inferring phylogenetic relationships and conducting species identification.
文摘BACKGROUND Depression is one of the most common and important psychological issues faced by dialysis patients.It can make it more difficult for them to adhere to their treatment regimen,which,in turn,can worsen their physical symptoms and lead to poorer health outcomes.AIM To examine the evolution and growth of publications related to dialysis and depression.The objectives were to identify the number of publications,the top active countries,the contributed institutions,funding agencies and journals,as well as to perform citation and research theme analysis.METHODS The search was conducted using the Scopus database for publications related to dialysis and depression between 1970 and 2022.Subsequently,bibliometric analysis was carried out on the data obtained using VOSviewer software,version 1.6.9.This analysis included visualization analysis,co-occurrence analysis and examination of publication trends in dialysis and depression.RESULTS We identified 800 publications that met the search criteria.The number of publications related to dialysis and depression has increased significantly in the past two decades.The USA led the way with 144 publications,which is 18%of all publications on this topic.Turkey came second with 88 publications(11%),followed by China with 55 publications(6.88%)and Iran with 52 publications(6.5%).Analysis of the research theme identified three main clusters related to gender differences in prevalence,identification of depression as a risk factor,and effective interventions to relieve depression.Future research direction analysis shows a shift toward effective interventions to relieve depression in dialysis patients.CONCLUSION This study provides a comprehensive overview of growth,trends and research themes related to dialysis and depression that could help researchers identify gaps in the literature and develop future research.
文摘BACKGROUND The global spread of severe acute respiratory syndrome coronavirus 2,responsible for coronavirus disease 2019(COVID-19),poses a significant risk to public health.Beyond the respiratory issues initially associated with the condition,severe cases of COVID-19 can also lead to complications in other organs,including the liver.Patients with severe COVID-19 may exhibit various clinical signs of liver dysfunction,ranging from minor elevations in liver enzymes without symptoms to more serious cases of impaired liver function.Liver damage is more commonly observed in patients with severe or critical forms of the disease.AIM To present the research landscape on COVID-19 and liver dysfunction while also offering valuable insights into the prominent areas of interest within this particular domain.METHODS On 18 February 2023,Scopus was utilised to conduct a comprehensive exploration of the relationship between COVID-19 and the liver dysfunction.The investigation encompassed the period from 1 January 2020 to 31 December 2022.Primary sources were meticulously examined and organised in a Microsoft Excel 2013 spreadsheet,categorised by journal,institution,funding agency,country and citation type.VOSviewer version 1.6.18 was employed to explore the prominent topics and knowledge network related to the subject.RESULTS There were 2336 publications on COVID-19 and liver dysfunction analysed in this study,of which 558 were published in 2020,891 in 2021 and 887 in 2022.Researchers from 111 different countries participated in the retrieved documents.The United States contributed the most studies,with 497 documents,representing 21.28%of the total,followed by China with 393 documents(16.82%)and Italy with 255 documents(10.92%).In the context of research related to COVID-19 and the liver,co-occurrence analysis identified three distinct clusters of topics:(1)‘COVID-19 vaccines in liver transplant recipients’;(2)‘liver function tests as a predictor of the severity and clinical outcomes in hospitalised patients’;and(3)‘care of patients with liver disease during the COVID-19 pandemic’.CONCLUSION This bibliometric study provides a comprehensive overview of liver-related publications in COVID-19 research over the past 3 years.This study highlights the significant contributions of high-income nations,particularly the United States,China,and Italy,to the production of liver-related scholarly literature in this field.Most of the articles focused on liver dysfunction in patients with COVID-19 and the implications of the virus for gastroenterologists and hepatologists.
文摘Objective:To assess the effectiveness and adverse drug reactions of all-oral regimens for patients with multidrug-resistant tuberculosis.Methods:This retrospective study was conducted at 10 Programmatic Management of Drug Resistant Tuberculosis sites in Punjab province of Pakistan.Patients receiving treatment for drug resistant tuberculosis from July 2019 to December 2020 with at least interim result i.e.6th month culture conversion or final outcomes(cured,complete,lost to follow-up,failure,death)available,were included in the study.Data was extracted from electronic data management system.For the reporting and management of adverse drug events,active tuberculosis drug safety monitoring and management was implemented across all sites.All the data was analyzed using SPSS version 22.Results:Out of 947 drug resistant tuberculosis patients included in this study,579(68%)of the patients had final outcomes available.Of these,384(67.9%)successfully completed their treatment.Out of 368(32%)patients who had their interim results available,all had their 6th month culture negative.Combining new medications was thought to result in serious adverse outcomes such as QT prolongation.However,this study did not record any severe adverse events among patients.Conclusions:All-oral regimens formulation guided by overall treatment effectiveness resulted in treatment outcomes comparable to those obtained with traditional injectable treatment.
文摘BACKGROUND Crohn’s disease represents a challenge for patients concerned with the modified diet regimen as well as practitioners who seek the best nutritional therapy.Crohn’s disease can alter the body’s ability to digest food and to absorb nutrients,resulting in severe vitamin deficiencies,malnutrition and sometimes lifethreatening complications.However,a comprehensive bibliometric analysis is lacking to map the current links between nutrition and Crohn’s disease in terms of the number of citations,geographic distribution and growth trends of publications.AIM To introduce the current state of research as well as hotspots in the field of nutrition and Crohn’s disease from a bibliometric standpoint.METHODS We searched the Scopus database and selected the relevant literature on nutrition and Crohn’s disease that met the inclusion criteria.We analyzed the publication trends and research hotspots by using video object segmentation viewer software.RESULTS We included 1237 publications.The number of documents published each year has increased steadily.The United States and the University of Otago,Christchurch,have had the highest productivity,with 208(16.81%)and 29(2.34%)documents,respectively.The“role of exclusive enteral nutrition for complicated Crohn’s disease”and“manipulation of the gut microbiota as a key target for Crohn’s disease”were the major research areas in 2016-2021,and they could be extensively investigated in the future.Meanwhile,research on“malnutrition in patients with Crohn’s disease”appeared to be an area that attracted more research attention before 2016.CONCLUSION This is the first bibliometric analysis to map the knowledge structure and trends regarding nutrition in Crohn’s disease research over the past two decades.The results provide a comprehensive summary and identification of the frontiers of nutrition and Crohn’s disease-related research,which may be used as a resource by researchers in the field.
基金supported by Chinese Medicine Pharmaceutical Key Discipline of Shaanxi province(No.303061107)National key Research and Development plan(No.2018-YFC1706904)+1 种基金Discipline Innovation team Project of Shaanxi University of Chinese Medicine(No.2019-YL11)Shaanxi Province Key subject of pharmacy engineering of Shaanxi Provincial Traditional Chinese Medicine administration(No.2017001).
文摘Objective:To predict and analyze the potential Q-markers of Chuanxiong Chatiao Prescription,and the pharmacokinetic properties of pulvis and pills in vivo were studied,which provided a basis for the rational evaluation of the phenomenon of“Different Dosage Forms of the Same Prescription”.Methods and Material:Q-markers analysis of Chuanxiong Chatiao Prescription based on the“Five Principles”(traceability and transmissibility,specificity,effectiveness,prescription compatibility and testability).The content determination method of Q-markers in Chuanxiong Chatiao Prescription was established by UPLC,and the content difference of Q-markers in the two dosage forms ware determined and compared.The Q-markers in rabbit plasma was determined by LC-MS/MS method,and the pharmacokinetic parameters of Q-markers in pulvis and pills were analyzed.Results:A total of 16 potential Q-markers from the“Five Principles”were used,nine components of tetramethylprazine,ferulic acid,glycyrrhizin,glycyrrhizic acid,luteolin,cimicifugoside,senkyunolideⅠ,isoimperatorin,nodakenin were identified as Q-markers of Chuanxiong Chatiao Presciption.The content of tetramethylprazine and other components in the pulvis form was found to be significantly higher than that in the pills,while the content of senkyunolideⅠwas lower than that in the pills,which may be related to the preparation process of the dosage form and the physicochemical properties of the components.Compared with pulvis,the Tmax and t_(1/2)of ferulic acid and other components in pills were significantly prolonged.To a certain extent,it can explain the classical theory of traditional Chinese medicine“Components in pulvis release quickly and take effect in fast-acting manner,while in pills release slowly and take effect in slow-acting”.Meanwhile,the Cmax and AUC0-t of tetramethylprazine and other components in pills were higher than those in pulvis,which showed unexpected pharmacokinetic characteristics,indicating the complexity of compounding and the importance of dosage form design.Conclusions:A method for the determination of Q-markers content was established by UPLC,which provide reference for the quality control of Chuanxiong Chatiao Prescription.In vivo studies have found the pharmacokinetic parameters indicate the absorption and distribution characteristics of pulvis and pills.However,it is also found that the release behavior of different components not only affected by the dosage form but also closely related to their own physical and chemical properties.
文摘BACKGROUND The gut microbiota plays a crucial role in gastrointestinal and overall health.Randomized clinical trials(RCTs)play a crucial role in advancing our knowledge and evaluating the efficacy of therapeutic interventions targeting the gut microbiota.AIM To conduct a comprehensive bibliometric analysis of the literature on RCTs involving the gut microbiota.METHODS Using bibliometric tools,a descriptive cross-sectional investigation was conducted on scholarly publications concentrated on RCTs related to gut microbiota,spanning the years 2003 to 2022.The study used VOSviewer version 1.6.9 to examine collaboration networks between different countries and evaluate the frequently employed terms in the titles and abstracts of the retrieved publications.The primary objective of this analysis was to identify key research areas and focal points associated with RCTs involving the gut microbiota.RESULTS A total of 1061 relevant articles were identified from the 24758 research articles published between 2003 and 2022.The number of publications showed a notable increase over time,with a positive correlation(R2=0.978,P<0.001).China(n=276,26.01%),the United States(n=254,23.94%),and the United Kingdom(n=97,9.14%)were the leading contributing countries.Københavns Universitet(n=38,3.58%)and Dankook University(n=35,3.30%)were the top active institutions.The co-occurrence analysis shows current gut microbiota research trends and important topics,such as obesity interventions targeting the gut microbiota,the efficacy and safety of fecal microbiota transplantation,and the effects of dietary interventions on humans.CONCLUSION The study highlights the rapid growth and importance of research on RCTs that involve the gut microbiota.This study provides valuable insight into research trends,identifies key players,and outlines potential future directions in this field.Additionally,the co-occurrence analysis identified important topics that play a critical role in the advancement of science and provided insights into future research directions in this field.
基金supported by National Hi-tech Research and Development Program of China (Grant No. 2006aa042439)
文摘For the purpose of solving the engineering constrained discrete optimization problem, a novel discrete particle swarm optimization(DPSO) is proposed. The proposed novel DPSO is based on the idea of normal particle swarm optimization(PSO), but deals with the variables as discrete type, the discrete optimum solution is found through updating the location of discrete variable. To avoid long calculation time and improve the efficiency of algorithm, scheme of constraint level and huge value penalty are proposed to deal with the constraints, the stratagem of reproducing the new particles and best keeping model of particle are employed to increase the diversity of particles. The validity of the proposed DPSO is examined by benchmark numerical examples, the results show that the novel DPSO has great advantages over current algorithm. The optimum designs of the 100?1 500 mm bellows under 0.25 MPa are fulfilled by DPSO. Comparing the optimization results with the bellows in-service, optimization results by discrete penalty particle swarm optimization(DPPSO) and theory solution, the comparison result shows that the global discrete optima of bellows are obtained by proposed DPSO, and confirms that the proposed novel DPSO and schemes can be used to solve the engineering constrained discrete problem successfully.
基金Supported by Department of Medicine,University of Saskat-chewan,and the College of Pharmacy and Nutrition,University of Saskatchewan
文摘AIM To determine the short-term biochemical effects and clinical tolerability of intermittent fasting(IF) in adults with type 2 diabetes mellitus(T2DM).METHODS We describe a three-phase observational study(baseline 2 wk, intervention 2 wk, follow-up 2 wk) designed to determine the clinical, biochemical, and tolerability of IF in community-dwelling volunteer adults with T2DM. Biochemical, anthropometric, and physical activity measurements(using the Yale Physical Activity Survey) were taken at the end of each phase. Participants reported morning, afternoon and evening self-monitored blood glucose(SMBG) and fasting duration on a daily basis throughout all study stages, in addition to completing a remote food photography diary three times within each study phase. Fasting blood samples were collected on the final days of each study phase. RESULTS At baseline, the ten participants had a confirmed diagnosis of T2DM and were all taking metformin, and on average were obese [mean body mass index(BMI) 36.90 kg/m^2]. We report here that a short-term periodof IF in a small group of individuals with T2DM led to significant group decreases in weight(-1.395 kg, P = 0.009), BMI(-0.517, P = 0.013), and at-target morning glucose(SMBG). Although not a study requirement, all participants preferentially chose eating hours starting in the midafternoon. There was a significant increase(P < 0.001) in daily hours fasted in the IF phase(+5.22 h), although few attained the 18-20 h fasting goal(mean 16.82 ± 1.18). The increased fasting duration improved at-goal(< 7.0 mmol/L) morning SMBG to 34.1%, from a baseline of 13.8%. Ordinal Logistic Regression models revealed a positive relationship between the increase in hours fasted and fasting glucose reaching target values(χ~2 likelihood ratio = 8.36, P = 0.004) but not for afternoon or evening SMBG(all P > 0.1). Postprandial SMBGs were also improved during the IF phase, with 60.5% readings below 9.05 mmol/L, compared to 52.6% at baseline, and with less glucose variation. Neither insulin resistance(HOMAIR), nor inflammatory markers(C-reactive protein) normalized during the IF phase. IF led to an overall spontaneous decrease in caloric intake as measured by food photography(Remote Food Photography Method). The data demonstrated discernable trends during IF for lower energy, carbohydrate, and fat intake when compared to baseline. Physical activity, collected by a standardized measurement tool(Yale Physical Activity Survey), increased during the intervention phase and subsequently decreased in the follow-up phase. IF was well tolerated in the majority of individuals with 6/10 participants stating they would continue with the IF regimen after the completion of the study, in a full or modified capacity(i.e., every other day or reduced fasting hours).CONCLUSION The results from this pilot study indicate that shortterm daily IF may be a safe, tolerable, dietary intervention in T2DM patients that may improve key outcomes including body weight, fasting glucose and postprandial variability. These findings should be viewed as exploratory, and a larger, longer study is necessary to corroborate these findings.
文摘This study investigated the effects and molecular mechanisms of genistein in improving insulin resistance induced by free fatty acids (FFAs) in HepG2 hepatocytes. A model of insulin resistance in HepG2 cells was established by adding palmitic acid (0.5 mmol/L) to the culture medium and the cells were treated by genistein. Glucose consumption of HepG2 cells was determined by glucose oxidase method. The levels of c-jun N-terminal kinase (JNK) phosphorylation, insulin receptor substrate-1 (IRS-1) Ser307 phosphorylation, JNK, IRS-1, phosphatidylinositol-3-kinase p85 (PI-3K p85) and glucose transporter 1 (GLUT1) proteins were detected by Western blotting. The results showed that after the treatment with palmitic acid for 24 h, the insulin-stimulated glucose transport in HepG2 cells was inhibited, and the glucose consumption was substantially reduced. Meanwhile, the expressions of IRS-1, PI-3K p85 protein and GLUT1 were obviously reduced, while the levels of JNK phosphorylation and IRS-1 Ser307 phosphorylation and the expression of JNK protein were significantly increased, as compared with cells of normal control. However, the aforementioned indices, which indicated the existence of insulin resistance, were reversed by genistein at 1-4 μmol/L in a dose-dependent manner. It was concluded that insulin resistance induced by FFAs in HepG2 hepatocytes could be improved by genistein. Genistein might reverse FFAs-induced insulin resistance in HepG2 cells by targeting JNK.
文摘AIM To investigate whether morin can reduce hepatic fibrosis by activating the NF-E2-related factor 2(Nrf2) signaling pathway.METHODS Twenty male Sprague-Dawley rats were randomly divided into four groups: control group, morin group, carbon tetrachloride(CCl4) group, and morin + CCl4 group. Rats in both the CCl4 and morin + CCl4 groups were injected intraperitoneally with CCl4 at a dose of 2 mL/kg twice a week. Rats in both the morin and morin + CCl4 groups were treated orally with morin at a dose of 50 mg/kg twice a week. Control rats were treated with vehicle only twice a week. At the end-point of the 8 wk of the experimental period, serum AST, ALT, and ALP were measured, and the liver specimenswere obtained for pathological assessment. Real-time PCR and Western blot methods were used to analyze the expression of α-smooth muscle actin(α-SMA), collagen Ⅰ, collagen Ⅲ, Nrf2, heme oxygenase(HO-1), and quinone oxidoreductase 1(NQO1) using frozen liver specimens.RESULTS Morin-treated rats in the morin + CCl4 group had less hyperplasia of fiber tissue, minimal inflammatory cells, and less body weight loss with favorable liver enzyme measurements compared to rats treated with CCl4 only. Additionally, morin-treated rats had significantly lower m RNA and protein expression of α-SMA, collagen Ⅰ, and collagen Ⅲ, but significantly higher m RNA and protein expression of Nrf2, HO-1, and NQO1 compared to rats treated with CCl4 only(P < 0.05).CONCLUSION Morin could play a protective role by inducing the expression of Nrf2 and its downstream antioxidant factors(HO-1 and NQO1) and reducing the expression of α-SMA, collagen Ⅰ, and collagen Ⅲ in CCl4-induced liver fibrosis rats.
基金Supported by the National Natural Science Foundation,No.81673241,No.81200634,No.81370982the program of Jiangsu Key Research Plan,No.BE2016698the International Science and Technology Cooperation Program of China,No.2013DFA32150
文摘AIM To investigate the dynamic alteration of mitochondrial carnitine palmitoyl transferase Ⅱ(CPT-Ⅱ) expression during malignant transformation of rat hepatocytes.METHODS Sprague-Dawley male rats were fed with normal, high fat(HF), and HF containing 2-fluorenylacetamide(2-FAA) diet, respectively. According to the Hematoxylin and Eosin staining of livers, rats were divided into control, fatty liver, degeneration, pre-cancerous, and cancerous groups. Liver lipids were dyed with Oil Red O, CPT-Ⅱ alterations were analyzed by immunohistochemistry, and compared with CPT-Ⅱ specific concentration(μg/mg protein). Levels of total cholesterol(Tch), triglyceride(TG), and aminotransferases [alanine aminotransferase(ALT), aspartate aminotransferase(AST)] were determined by the routine methods.RESULTS After intake of HF and/or HF+2-FAA diets, the rat livers showed mass lipid accumulation. The lipid level in the control group was significantly lower than that in other groups. The changes of serum TG and Tch levels were abnormally increasing, 2-3 times more than those in the controls(P < 0.05). During the rat liver morphological changes from normal to cancer development process with hepatocyte injury, serum AST and ALT levels were significantly higher(4-8 times, P < 0.05) than those in the control group. The specific concentration of CPT-Ⅱ in liver tissues progressively decreased during hepatocyte malignant transformation, with the lowest CPT-Ⅱ levels in the cancer group than in any of the other groups(P < 0.05).CONCLUSION Low CPT-Ⅱ expression might lead to abnormal hepatic lipid accumulation, which should promote the malignant transformation of hepatocytes.
