Levels of evidence and grades of recommendation supporting European society for medical oncology clinical practice guidelines

Background:The European Society for Medical Oncology(ESMO)guidelines are among the most comprehensive and widely used clinical practice guidelines(CPGs)globally.However,the level of scientific evidence supporting ESMO CPG recommendations has not been systematically investigated.This study assessed ESMO CPG levels of evidence(LOE)and grades of recommendations(GOR),as well as their trends over time across various cancer settings.Methods:We manually extracted every recommendation with the Infectious Diseases Society of America(IDSA)classification from each CPG.We examined the distribution of LOE and GOR in all available ESMO CPG guidelines across different topics and cancer types.Results:Among the 1,823 recommendations in the current CPG,30%were classified as LOEⅠ,and 43%were classified as GOR A.Overall,there was a slight decrease in LOEⅠ(−2%)and an increase in the proportion of GOR A(+1%)in the current CPG compared to previous versions.The proportion of GOR A recommendations based on higher levels of evidence such as randomized trials(LOEⅠ–Ⅱ)shows a decrease(71%vs.63%,p=0.009)while recommendations based on lower levels of evidence(LOEⅢ–Ⅴ)show an increase(29%vs.37%,p=0.01)between previous and current version.In the current versions,the highest proportion of LOEⅠ(42%)was found in recommendations related to pharmacotherapy,while the highest proportion of GOR A recommendations was found in the areas of pathology(50%)and diagnostic(50%)recommendations.Significant variability in LOEⅠand GOR A recommendations and their changes over time was observed across different cancer types.Conclusion:One-third of the current ESMO CPG recommendations are supported by the highest level of evidence.More well-designed randomized clinical trials are needed to increase the proportion of LOEⅠand GOR A recommendations,ultimately leading to improved outcomes for cancer patients.

Short-term efficacy and influencing factors of conventional chemotherapy combined with irinotecan in patients with advanced gastric cancer

BACKGROUND Gastric cancer is one of the most common cancers worldwide, with a 5-year survival rate of only 20%. The age of onset of gastric cancer is in line with the general rule of cancer. Most of them occur after middle age, mostly between 40and 60 years old, with an average age of about 50 years old, and only 5% of patients are under 30 years old. The incidence of male is higher than that of female.AIM To investigate the short-term efficacy and influencing factors of chemotherapy combined with irinotecan in patients with advanced gastric cancer.METHODS Eighty patients with advanced gastric cancer who were treated in our hospital from January 2019 to January 2022 were selected. The patients were divided into an observation group(n = 40) and control group(n = 40) by the envelope method.The control group was given preoperative routine chemotherapy. The observation group was treated with irinotecan in addition to the chemotherapy given to the control group. The short-term efficacy of treatment in the two groups, as well as tumor marker levels and quality of life before and after treatment were evaluated.RESULTS The short-term treatment effect in the observation group was better than that in the control group(P < 0.05), and the total effective rate was 57.50%. The age and proportion of tumor node metastasis(TNM) stage IV patients with ineffective chemotherapy in the observation group were(65.12 ± 5.71) years and 52.94%,respectively, which were notably higher than those of patients with effective chemotherapy(P < 0.05), while the Karnofsky Performance Scale score was(67.70± 3.83) points, which was apparently lower than that of patients with effective chemotherapy(P <0.05). After 3 mo of treatment, the SF-36 scale scores of physiological function, energy, emotional function, and mental health in the observation group were 65.12 ± 8.14, 54.76 ± 6.70, 47.58 ± 7.22,and 66.16 ± 8.11 points, respectively, which were considerably higher than those in the control group(P < 0.05). The incidence rates of grade Ⅲ-Ⅳ diarrhea and grade Ⅲ-Ⅳ thrombocytopenia in the observation group were 32.50% and 25.00%, respectively, which were markedly higher than those in the control group(P < 0.05).CONCLUSION Chemotherapy combined with irinotecan in patients with advanced gastric cancer has a good short-term efficacy and can significantly reduce serum tumor markers and improve the quality of life of patients. The efficacy may be affected by the age and TNM stage of the patients, and its long-term efficacy needs further study.

The Managerial Role of Pharmacist at Community Pharmacy Setting in Saudi Arabia

In Saudi Arabia community pharmacies by law, be owned and managed by pharmacists. Although these two functions seemed to be the same but in reality, they are not. Some studies showed that in community pharmacy managerial functions account for more than 50% of total routine and critical activity for all managerial position surveyed while other study showed that only 13.6% of the pharmacist’s time spent in administrative activities. This article addressed the role of the pharmacist as manager and the way in which he/she manages the pharmacy to ensure optimum productivity. The main part of this review discussed the managerial role of pharmacist in management of human resources, financial resources, marketing, inventory, information resources and space management of the pharmacy. Additionally, the management process, professional skills of managers, development of managerial skills, problems in management process and their resolution were also discussed. In addition to management functions which also include planning, organizing, leading, and controlling processes. The author concluded that the skills of pharmacy managers may vary because of the lack of formalized management training programs. To bridges a gap in management education, interested pharmacists should be encouraged to shift their career goals from professional to pharmacy administration. In addition, expansion of curricula in pharmacy management to include management training of highest possible caliber in managerial skills is highly demanded. Formalized management training programs for those involved in community pharmacy practice are also warranted.

Intention and hesitancy to receive a booster dose of COVID-19 vaccine among pregnant women using a health belief model: A cross-sectional study

Objective:To examine the pattern of COVID-19 infection and vaccination,and to explore pregnant women’s willingness and reluctance to accept a booster dose of the COVID-19 vaccine.Methods:This was a cross-sectional,descriptive study with a convenient sample size using a structured questionnaire among pregnant women attending the gynecology and obstetrics department at Acıbadem Mehmet Ali Aydinlar Hospital,Istanbul,Türkiye.The Health Belief Model scale was used to assess the intention and reluctance to accept a booster dose of the COVID-19 vaccine.Results:A total of 145 participants,with a mean age of(33.5±4.8)years,and a gestational age of(30.9±7.3)weeks,were enrolled in this study.88.8%Received full doses of the Pfizer-BioNTech vaccination.47.8%Participants suffered from vaccine adverse effects.Health Belief Model demonstrated a significant finding of perceived susceptibility(P<0.001),perceived severity of COVID-19 complications(P<0.001),and perceived benefits regarding a booster COVID-19 vaccination(P<0.001).Conclusions:Most pregnant women who received the COVID-19 immunization express a significant intention to receive a booster dose,regardless of the adverse effects experienced from the previous doses.However,a small percentage of the study sample express hesitancy about receiving the booster dose.

Comparing the efficacy of regen-cov,remdesivir,and favipiravir in reducing invasive mechanical ventilation need in hospitalized COVID-19 patients

BACKGROUND Coronavirus disease 2019(COVID-19)pandemic stimulates research works to find a solution to this crisis from starting 2020 year up to now.With ending of the 2021-year,various advances in pharmacotherapy against COVID-19 have emerged.Regarding antiviral therapy,casirivimab and imdevimab antibody combination is a type of new immunotherapy against COVID-19.Standard antiviral therapy against COVID-19 includes Remdesivir and Favipiravir.AIM To evaluate the efficacy of antibodies cocktail(casirivimab and imdevimab)compared to standard antiviral therapy in reducing the need for invasive mechanical ventilation(IMV).METHODS 265 COVID-19 polymerase chain reaction confirmed patients with indication for antiviral therapy were included in this study and were divided into 3 groups(1:2:2):Group A:REGN3048-3051 antibodies cocktail(casirivimab and imdevimab),group B:Remdesivir,group C:Favipiravir.The study design is a single-blind nonrandomized controlled trial Mansoura University Hospital owns the study’s drugs.The duration of the study was about 6 mo after ethical approval.RESULTS Casirivimab and imdevimab achieve less need for O2 therapy and IMV,with less duration of this need than remdesivir and favipiravir.CONCLUSION Group A(casirivimab and imdevimab)achieve better clinical outcomes than groups B(remdesivir)and C(favipiravir)intervention groups.

Investigational treatments for neurodegenerative diseases caused by inheritance of gene mutations:lessons from recent clinical trials

We reviewed recent major clinical trials with investigational drugs for the treatment of subjects with neurodegenerative diseases caused by inheritance of gene mutations or associated with genetic risk factors.Specifically,we discussed randomized clinical trials in subjects with Alzheimer's disease,Huntington's disease and amyotrophic lateral sclerosis bearing pathogenic gene mutations,and glucocerebrosidase-associated Parkinson's disease.Learning potential lessons to improve future therapeutic approaches is the aim of this review.Two long-term,controlled trials on three anti-β-amyloid monoclonal antibodies(solanezumab,gantenerumab and crenezumab)in subjects carrying Alzheimer's disease-linked mutated genes encoding for amyloid precursor protein or presenilin 1 or presenilin 2 failed to show cognitive or functional benefits.A major trial on tominersen,an antisense oligonucleotide designed to reduce the production of the huntingtin protein in subjects with Huntington's disease,was prematurely interrupted because the drug failed to show higher efficacy than placebo and,at highest doses,led to worsened outcomes.A 28-week trial of tofersen,an antisense oligonucleotide for superoxide dismutase 1 in patients with amyotrophic lateral sclerosis with superoxide dismutase 1 gene mutations failed to show significant beneficial effects but the 1-year open label extension of this study indicated better clinical and functional outcomes in the group with early tofersen therapy.A trial of venglustat,a potent and brain-penetrant glucosylceramide synthase inhibitor,in Parkinson's disease subjects with heterozygous glucocerebrosidase gene mutations revealed worsened clinical and cognitive performance of patients on the enzyme inhibitor compared to placebo.We concluded that clinical trials in neurodegenerative diseases with a genetic basis should test monoclonal antibodies,antisense oligonucleotides or gene editing directed against the mutated enzyme or the mutated substrate without dramatically affecting physiological wild-type variants.

Fixed-Dose Combination (FDC) Formulation of Quinine Sulphate-Doxycycline (Qidox) for Malaria Therapy

Background: One of the deadliest parasite infections is malaria. A combination of quinine sulphate and doxycycline is another therapeutic option for malaria that is resistant to chloroquine and is anticipated to be able to both combat the issue of anti-malarial medication resistance as well as the compliance to malaria therapy that is still raging in certain locations of Indonesia. Aim: This study will focus on evaluating the possibility of interaction between quinine sulphate and doxycycline followed by formulating the fixed-dose combination of both active pharmaceutical ingredients. Method: The study was designed as a laboratory experiment and applied some examinations. The examination from the organoleptic test of active pharmaceutical ingredients powder, crystallography analysis, and physical analysis of fixed-dose tablet including hardness, friability, and disintegration time testing. Result: The crystallography study reported there was no physical interaction found between quinine sulphate and doxycycline. The formula found excellent tablet printability with a composition of Quinine sulphate and doxycycline (Qidox). Conclusion: quinine sulphate with doxycycline can be combined into one tablet as Fixed-Dose Combination (FDC).

Role of glioma immune biomarker ORMDL2 in the diagnosis and prognosis of glioma

Obiective:To investigate the prognostic value of ORMDL2 in human glioma and its relationship with immune invasion.Methods:The clinical survival data from TCGA-LGG&GBM,CGGA and GEO were used to evaluate the clinical prognostic value of ORMDL2.The cut off value of ORMDL2 was detected with pROC package to draw ROC curve to prove its value in differential diagnosis of glioma.The first 300 genes with the most significant positive correlation with ORMDL2 were selected to establish PPI network through STRING database and conduct GO and pathway analysis.The relationship between the expression of ORMDL2 mRNA and immune cell infiltration was investigated by using ssGSEA and TIMER2.0 databases.Results:The expression of ORMDL2 mRNA in glioma was significantly higher than that in adjacent normal tissues,and the difference was most significant in high-grade glioma.The expression of ORMDL2 was increased in human glioma,which was related to the clinicopathological characteristics and poor prognosis of glioma patients.In addition,the increased expression of ORMDL2 was associated with a series of immune infiltrating cells,including macrophages.Conclusion:ORMDL2 plays an important role in glioma immune cell infiltration and is a biomarker of prognosis of glioma patients.

Urinary Tract Infections in a Tunisian Orthopedic Institute: Major Strain Microbiological Profile

Background: Urinary Tract Infection (UTI) detected in the hospital and in the community is one of the most common reasons for consultation in everyday practice;it represents a major source of antibiotic consumption. This study’s objectives were to outline the microbiological profile of Tunisian patients with UTI and assess antibiotic resistance over the course of three years at the Orthopedic Institute. Methods: All strains identified in urine samples between January 1st, 2019, and December 31st, 2021, were included. Standard laboratory procedures were used to identify the bacterium. The Microscan Walkway 40 Plus was used to do biochemical assays and antibiotic susceptibility testing. The EUCAST criteria were used to interpret the findings. Results: A total of 1313 strains were isolated. The bacteriological study showed the predominance of enterobacteria (96.8%), especially E. coli (52.2%) and K. pneumoniae (19.3%). Overall resistance rates to antimicrobial agents were as follows: for hospital, E. coli strains were in descending order amoxicillin (73.05%), trimeth/sulfamethoxazole (46.9%), ofloxacin (40.3%), amoxicillin/clavulanic acid (35.05%) and gentamicin (20.5%). Our results showed low resistance to fosfomycin for E. coli 2.6% in hospitals while ≥12.1% for K. pneumoniae. Amikacin resistance remains medium-low for E. coli being ≥20% and 10% for K. pneumonia. Nitrofuran resistance has affected 1.06% of E. coli strains in hospital settings and 21.5% of K. pneumoniae. Extended Spectrum Beta-Lactamases (ESBLs) production was present in a number of enterobacteria (19.3% of K. pneumoniae and 14.4% of E. coli). Conclusion: The prevalence of E. coli and K. pneumoniae producers ESBLs in UTI is increasing. Rigorous surveillance of resistance rate is necessary to determine appropriate empirical treatment and limit the spread of multiresistant strains.

Unveiling the hidden world of gut health:Exploring cutting-edge research through visualizing randomized controlled trials on the gut microbiota

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.

Effect of Rituximab Versus Mycophenolate Mofetil or Cyclophosphamide as Control in Lupus Nephritis:A Meta-Analysis

Objective:To evaluate the effects of rituximab versus mycophenolate mofetil or cyclophosphamide as control in lupus nephritis by meta-analysis.Methods:A systematic search was carried out up to January 2022,obtaining 7 studies involving 645 participants with lupus nephritis at the commencement of the investigation;198 of them were treated with rituximab,while 447 were treated with mycophenolate mofetil or cyclophosphamide.We determined the odds ratio(OR)and mean difference(MD)with 95%confidence index(CI)to compare rituximab’s efficacy to that of mycophenolate mofetil or cyclophosphamide as control in lupus nephritis using random-or fixed-effects model by dichotomous or continuous techniques.Results:The rituximab group showed significantly higher complete renal remission rate(OR=2.52;95%CI 1.30-4.91,P=0.006)and total renal remission rates(OR=2.22;95%CI 1.36-3.63,P=0.001)than the control group.However,there was no significant difference in terms of end Systemic Lupus Erythematosus Disease Activity Index(SLEDAI)score(MD-1.16;95%CI-2.88-0.57,P=0.19),proteinuria(MD-0.31;95%CI-0.70-0.09,P=0.013),and serum creatinine(MD 0.01;95%CI-0.04-0.07,P=0.64)between the rituximab group and the control.Conclusion:Rituximab exhibited significantly greater complete renal remission rate and total renal remission rates,with no significant difference in terms of shorter-end SLEDAI,proteinuria,and serum creatinine,compared with the control in individuals with lupus nephritis.

Inflammatory Bowel Disease Patients’Risk of Developing Prostate Cancer:A Meta-Analysis

Background:Inflammatory bowel disease(IBD)has been linked to an increased risk of prostate cancer(PC)in numerous studies.However,the exact relationship between them remains conflicting.In this meta-analysis,we focus on determining the relationship between PC incidence and IBD.Methods:A comprehensive literature search was conducted up until January 2022,selecting 14 studies,comprising 127,323 subjects with IBD,at the beginning of the study,among which 61,985 were patients with ulcerative colitis(UC)and 37,802 were with Crohn’s disease(CD).The studies reported the differences between subjects with IBD and controls with regard to the incidence of PC.In order to investigate the relationship between IBD and the prevalence of PC,we estimated the odds ratio(OR)with 95%confidence intervals(CIs).Results:IBD significantly increased the incidence of PC(OR,3.46;95%CI,1.40-8.54,P=0.007)compared to controls.UC significantly increased the incidence of PC(OR,1.43;95%CI,1.03-1.98,P=0.03)compared to controls.Yet,no significant difference was observed between CD and controls in relation to PC incidence(OR,0.89;95%CI,0.75-1.06,P=0.18).Conclusion:IBD,particularly UC,may increase the risk of developing PC.This relationship prompts us to advocate for increased PC and IBD screening to reduce the risk for possible complications that could occur in these subjects.

A Meta-Analysis of the Effectiveness of Vitamin C in the Prevention and Treatment of Childhood Upper Respiratory Tract Infections

Background:The effectiveness of vitamin C in the prevention and treatment of pediatric upper respiratory tract infections was evaluated in a meta-analysis.Methods:A total 2,573 children with upper respiratory tract infections were included in the meta-analysis,1,280 of whom received vitamin C and 1,293 who received control medication.The analysis of findings related to the studies included was done through random or fixed effects model to determine whether vitamin C supplementation could stop and control upper respiratory tract infections in children using mean difference(MD)with 95%confidence intervals(CIs).Results:On average,vitamin C-treated children had fewer upper respiratory tract infection bouts,their illness lasted shorter(MD-0.84;95%CI-1.47 to-0.20,P=0.009),and they were less contagious than the control.Conclusions:The number of episodes and illness duration of upper respiratory tract-infected pediatric subjects were considerably reduced in the intervention group(vitamin C)compared to the control.Due to the small sample size in four of 11 studies and the limited number of studies included for comparison,the outcomes should be carefully examined.

Evaluation of antibiotic use among inpatients in surgical ward at Mbarara Regional Referral Hospital,South-Western Uganda

Objective The main aim of this study was to evaluate antibiotic use among inpatients in surgical ward at South-Mbarara Regional Referral Hospital,South-Western Uganda.Methodology:A retrospective cross-sectional study was carried out on patients'follow-up forms of Mbarara Regional Referral Hospital,surgical ward from 15th November to 15th December.Data abstraction tool was employed to extracted data,entered in excel version 2010 then imported into SPSS software version 2010 where different variables were analyzed.Results:A total of 136 patient forms were studied.At least one antibiotic was prescribed in 76(56%).Majority(81.58%)of the antibiotics were prescribed for therapeutic purpose while some lacked documented and approved indications.Specific indications were not documented in 15(19.73%)of the forms.Sepsis without culture and sensitivity was the most frequent indication 14(18.42%)for antibiotics followed by prophylactic use 12(15.79%).Ceftriaxone was the most commonly(82.9%)prescribed antibiotic;followed by metronidazole for 31(40.8%)and Ampicillin/Cloxacillin for 8(10.5%)of the patients.Out of the 76 patients who used antibiotics,the overall use was found to be appropriate in only 20(26.3%).Most prescriptions had right doses 57(75.0%)followed by right frequencies 53(69.7%);whereas the duration was the least appropriate with only 46(60.5%)of the 76 patients.Conclusion:More than half of the patients had at least one antibiotic prescribed to them.Ceftriaxone and metronidazole were the most prescribed,the majority of antibiotics were used for treatment and some of the patients were on antibiotics without specific indications.Sepsis was the most common indication for the antibiotics used.Most antibiotics were inappropriately used.Duration of treatment was the most inappropriate parameter and antibiotic use varied greatly with guidelines.

Phytochemical composition and toxicity assessment of Ammi majus L.

Objective:To assess the acute and subacute toxicity as well as the phytochemical composition of two extracts and three fractions of Ammi majus L.Methods:The aqueous extracts were prepared separately by maceration for 48 h and by infusion for 1 h,while the fractions were prepared by the Soxhlet extractor,successively employing cyclohexane,ethyl acetate,and ethanol.The acute toxicity study was carried out in accordance with the OECD N°423 guideline at a single dose(2000 mg/kg)in mice for 14 days.The subacute toxicity study was performed by a daily oral administration of 250 mg/kg 2 for 10 d and 100 mg/kg doses for 28 d.Phytochemical screening was performed using staining and precipitation reactions,while the chemical characterization of some analytes was detected by HPLC-MS/MS analysis.Results:In the acute toxicity study,no signs of toxicity such as convulsion,salivation,diarrhea,sleep and coma were observed during 30 minutes and 14 days,so the lethal dose was higher than 2000 mg/kg for each extract and fraction.The subacute toxicity results showed that at a dose of 250 mg/kg,61.10%of the animals died and the rest developed morbidity.On the other hand,at a dose of 100 mg/kg,all the animals were still alive after 28 days,with no morbidity and the biochemical parameters were normal with no abnormalities in the liver,kidneys and pancreas.Phytochemical screening indicated the presence of flavonoids,tannins,coumarins,and free quinones and the absence of alkaloids and anthocyanins.Conclusions:The extracts and fractions of Ammi majus L.are not toxic in the short and long term with a varied chemical composition.Toxicological tests on animals other than rodents and in the long term(more than 28 days)are needed to further confirm the safety of Ammi majus extracts.

Anemarsaponin B mitigates acute pancreatitis damage in mice through apoptosis reduction and MAPK pathway modulation

Background:Acute pancreatitis(AP),known for its rapid onset and significant incidence and mortality rates,presents a clinical challenge due to the limited availability of effective treatments and preventive measures.Anemarsaponin B(ASB)has emerged as a potential therapeutic agent,demonstrating capabilities in reducing immune inflammation,positioning it as a promising candidate for AP treatment.Methods:We investigated the effects of ASB on AP in mice,induced by caerulein and lipopolysaccharide(LPS).Peripheral blood samples were collected 24 h post-induction with caerulein to assess of key biomarkers including lipase,amylase,TNF-α,IL-1β,IL-6,SOD,and GSH-Px.A range of techniques such as immunohistochemistry staining,immunofluorescence staining,Western blotting,and quantitative Polymerase Chain Reaction(q-PCR),were employed to measure the expression of critical genes.Additionally,pancreas samples from the mice were harvested for microbiome and metabolome sequencing,with the data analyzed to understand the impact of ASB on AP.Results:Our study revealed that,compared to the sham group,the AP group exhibited significantly higher serum levels of lipase,amylase,and cytokines,while levels of SOD and GSH Px were notably lower.Treatment with ASB led to a substantial decrease in the levels of lipase,amylase,and cytokines,and an increase in SOD and GSH-Px levels.q-PCR analysis of pancreatic histiocytes corroborated these serum findings.Hematoxylin and Eosin(H&E)staining indicated significant alterations in the pathological changes in the pancreas,lungs,and small intestine of the AP model due to ASB.Immunofluorescence assays demonstrated that ASB alleviated the apoptosis of pancreatic histiocytes in the AP model.Western Blot and histological analyses showed that ASB reduced the phosphorylation of TAK,p38,JNK,and ERK proteins,as well as the levels of TRAF6 protein in the AP model.Furthermore,metabolomic and gut microbiota analysis identified 27 differential metabolites and 34 differential species.The combined metabolome and microbiome analysis suggested an association between certain microbes(e.g.,unclassified-Saprospiraceae and unclassified-Micavibrionales)and metabolites(e.g.,LysoPE(0:0/20:0),PC(DiMe(13,5)/PGJ2)),and Heptanoic acid,indicating potential pathways through which ASB may exert its therapeutic effects in AP.Conclusions:ASB exhibits therapeutic efficacy in treating AP induced by caerulein combined with lipopolysaccharide(LPS),primarily through modulating the mitogenactivated protein kinase(MAPK)signaling pathway.This discovery offers fresh perspectives for AP drug development,underscoring the potential of targeting specific cellular pathways.Additionally,the intricate interplay observed between the gut microbiota and metabolites following ASB treatment highlights novel therapeutic targets,suggesting that manipulating the gut microbiome and metabolome could be a viable strategy in AP management.These findings pave the way for further research into comprehensive treatment approaches that incorporate both pharmacological intervention and microbiota modulation.

Chemokine-like factor 1 (CKLF1) is expressed in myocardial ischemia injury in vivo and in vitro

Introduction:Chemokine-like factor 1(CKLF1)is a chemokine that is overexpressed in several diseases.Our previousfindings revealed a significant increase in CKLF1 expression in the ischemic brain,suggesting its potential as a therapeutic target for ischemic stroke.Methods:In this study,we examined the expression dynamics of CKLF1 in both in vivo and in vitro models of ischemic cardiac injury.Myocardial infarction(MI)was induced in vivo by ligation of the left anterior descending artery(LAD)of the rat heart.The levels of CKLF1,Creatine Kinase MB Isoenzyme(CK-MB),and Lactate dehydrogenase(LDH)in the serum were detected using Enzyme-linked immunosorbent assay(ELISA).The expression of CKLF1 in the infarcted area was detected by immunohistochemistry,immunofluorescence,quantitative PCR(qPCR),and Western blotting(WB).H9C2 and AC16 cardiomyocytes cultured in vitro were subjected to oxygen and glucose deprivation(OGD).LDH was used to detect cell damage,and CKLF1 expression was detected by qPCR and WB.Results:CKLF1 mRNA and protein expression were significantly increased in h9c2 cells at 1.5 h and in AC16 cells at 4 h after OGD.The serum CK-MB in rats increased significantly on thefirst day after infarction,while the LDH concentration increased significantly on the third day after infarction.CKLF1 blood levels significantly increased on thefirst day following MI in rats.CKLF1 expression notably increased in the infarct area on days 1,3,and 7 post-MI.In MI tissue,CKLF1 colocalizes with cardiomyocytes,macrophages,and neutrophils.Conclusion:CKLF1 was substantially expressed during myocardial ischemia injury both in vivo and in vitro and was colocalized with macrophages and neutrophils,indicating that CKLF1 is expected to be a biomarker and a drug target for the treatment of myocardial infarction.

Hepatoprotective and antioxidant effects of lycopene on non-alcoholic fatty liver disease in rat

AIM To evaluate the hepatoprotective effect of lycopene(Ly) on non-alcoholic fatty liver disease(NAFLD) in rat. METHODS A rat model of NAFLD was first established by feeding a high-fat diet for 14 wk. Sixty-five rats were randomly divided into normal group, model group and Ly treatment groups. Alanine aminotransferase(ALT), aspartate aminotransferase(AST), triglycerides(TG), total cholesterol(TC) in serum and low density lipoproteincholesterol(LDL-C), high density lipoprotein-cholesterol(HDL-C), free fatty acid(FFA), malondialdehyde(MDA), superoxide dismutase(SOD), glutathione(GSH) in liver tissue were evaluated, respectively. While the hepatoprotective effect was also confirmed by histopathological analysis, the expression levels of TNF-α and cytochrome P450(CYP) 2E1 in rat liver were determined by immunohistochemistry analysis.RESULTS A significant decrease was observed in the levels of serum AST(2.07-fold), ALT(2.95-fold), and the blood lipid TG(2.34-fold) and TC(1.66-fold) in the dose of 20 mg/kg Ly-treated rats(P < 0.01), compared to the model group. Pretreatment with 5, 10 and 20 mg/kg of Ly significantly raised the levels of antioxidant enzyme SOD in a dose-dependent manner,to 90.95 ± 9.56, 109.52 ± 11.34 and 121.25 ± 10.68(P < 0.05, P < 0.01), as compared with the model group. Similarly, the levels of GSH were significantly increased(P < 0.05, P < 0.01) after the Ly treatment. Meanwhile, pretreatment with 5, 10 and 20 mg/kg of Ly significantly reduced MDA amount by 30.87, 45.51 and 54.49% in the liver homogenates, respectively(P < 0.01). The Ly treatment group showed significantly decreased levels of lipid products LDL-C(P < 0.05, P < 0.01), improved HDL-C level and significantly decreased content of FFA, compared to the model group(P < 0.05, P < 0.01). Furthermore, the Ly-treated group also exhibited a down-regulated TNF-α and CYP2E1 expression, decreased infiltration of liver fats and reversed histopathological changes, all in a dosedependent manner(P < 0.05, P < 0.01). CONCLUSION This study suggests that Ly has a protective effect on NAFLD, down-regulates expression of TNF-α, and that CYP2E1 may be one of the action mechanisms for Ly.