Human normal flora is a source of probiotics.The safety characteristics of a specific isolate determine its application in foods or drugs.The food-borne-pathogen antagonist strain Lactobacillus gasseri HMV18 is one of...Human normal flora is a source of probiotics.The safety characteristics of a specific isolate determine its application in foods or drugs.The food-borne-pathogen antagonist strain Lactobacillus gasseri HMV18 is one of the isolates from normal human flora.In this work,we assessed the in vitro pH tolerance,bile tolerance,biogenic amine production,mucin utilization,and safety of in vivo administration to mice to evaluate general health,organ-body weight index,organ histopathological change,whether L.gasseri HMV18 can colonize in the gut or modulate the gut microbiota after oral administration.The results suggest that L.gasseri HMV18 can tolerate pH 3 for 2 h,3%bile for 3 h,biogenic amine negative,mucin usage negative,does not encode verified toxins,and cause no visible change in mice's organs.L.gasseri HMV18 might not colonize in mice's gut,but can significantly affect the structure of gut microbiota.A bibliographical survey suggested that there were as few as 8 opportunistic infection cases from 1984 to 2022 and that the possibility for L.gasseri to cause infection is relatively low.Therefore,this work provides a basis for the foods or drugs application of L.gasseri HMV18 and gives a map of experiments for the safety assessment of probiotics.展开更多
Patients and physicians understand the importance of self-care following spinal cord injury (SCI), yet many individuals with SCI do not adhere to recommended self-care activities despite logistical supports. Neurobeha...Patients and physicians understand the importance of self-care following spinal cord injury (SCI), yet many individuals with SCI do not adhere to recommended self-care activities despite logistical supports. Neurobehavioral determinants of SCI self-care behavior, such as impulsivity, are not widely studied, yet understanding them could inform efforts to improve SCI self-care. We explored associations between impulsivity and self-care in an observational study of 35 US adults age 18 - 50 who had traumatic SCI with paraplegia at least six months before assessment. The primary outcome measure was self-reported self-care. In LASSO regression models that included all neurobehavioral measures and demographics as predictors of self-care, dispositional measures of greater impulsivity (negative urgency, lack of premeditation, lack of perseverance), and reduced mindfulness were associated with reduced self-care. Outcome (magnitude) sensitivity, a latent decision-making parameter derived from computationally modeling successive choices in a gambling task, was also associated with self-care behavior. These results are preliminary;more research is needed to demonstrate the utility of these findings in clinical settings. Information about associations between impulsivity and poor self-care in people with SCI could guide the development of interventions to improve SCI self-care and help patients with elevated risks related to self-care and secondary health conditions.展开更多
The coronavirus disease 2019(COVID-19)represents a global health and economic challenge.Hepatic injuries have been approved to be associated with severe acute respiratory syndrome coronavirus(SARS-CoV-2)infection.The ...The coronavirus disease 2019(COVID-19)represents a global health and economic challenge.Hepatic injuries have been approved to be associated with severe acute respiratory syndrome coronavirus(SARS-CoV-2)infection.The viral tropism pattern of SARS-CoV-2 can induce hepatic injuries either by itself or by worsening the conditions of patients with hepatic diseases.Besides,other factors have been reported to play a crucial role in the pathological forms of hepatic injuries induced by SARS-CoV-2,including cytokine storm,hypoxia,endothelial cells,and even some treatments for COVID-19.On the other hand,several groups of people could be at risk of hepatic COVID-19 complications,such as pregnant women and neonates.The present review outlines and discusses the interplay between SARS-CoV-2 infection and hepatic injury,hepatic illness comorbidity,and risk factors.Besides,it is focused on the vaccination process and the role of developed vac-cines in preventing hepatic injuries due to SARS-CoV-2 infection.展开更多
Objective Arsenic(As) and fluoride(F) are two of the most common elements contaminating groundwater resources. A growing number of studies have found that As and F can cause neurotoxicity in infants and children, lead...Objective Arsenic(As) and fluoride(F) are two of the most common elements contaminating groundwater resources. A growing number of studies have found that As and F can cause neurotoxicity in infants and children, leading to cognitive, learning, and memory impairments. However, early biomarkers of learning and memory impairment induced by As and/or F remain unclear. In the present study, the mechanisms by which As and/or F cause learning memory impairment are explored at the multi-omics level(microbiome and metabolome).Methods We stablished an SD rats model exposed to arsenic and/or fluoride from intrauterine to adult period.Results Arsenic and/fluoride exposed groups showed reduced neurobehavioral performance and lesions in the hippocampal CA1 region. 16S rRNA gene sequencing revealed that As and/or F exposure significantly altered the composition and diversity of the gut microbiome, featuring the Lachnospiraceae_NK4A136_group, Ruminococcus_1, Prevotellaceae_NK3B31_group, [Eubacterium]_xylanophilum_group. Metabolome analysis showed that As and/or F-induced learning and memory impairment may be related to tryptophan, lipoic acid, glutamate, gamma-aminobutyric acidergic(GABAergic) synapse, and arachidonic acid(AA) metabolism. The gut microbiota, metabolites, and learning memory indicators were significantly correlated.Conclusion Learning memory impairment triggered by As and/or F exposure may be mediated by different gut microbes and their associated metabolites.展开更多
Objective:To investigate the relationship between triterpenoid saponin content and antioxidant,antimicrobial,and α-glucosidase inhibitory activities of 70%ethanolic,butanolic,aqueous,supernate and precipitate extract...Objective:To investigate the relationship between triterpenoid saponin content and antioxidant,antimicrobial,and α-glucosidase inhibitory activities of 70%ethanolic,butanolic,aqueous,supernate and precipitate extracts of Juglans regia leaves.Methods:Triterpenoid saponins of different Juglans regia leaf extracts were measured by the vanillin method.Antioxidant activity was evaluated against DPPH and ABTS free radicals.We also assessed α-glucosidase inhibitory and antimicrobial activities of the leaf extracts.Pearson’s correlation coefficient was evaluated to determine the correlation between the saponin content and biological activities.Results:The butanolic extract was most effective against DPPH with an IC50of 6.63μg/mL,while the aqueous extract showed the highest scavenging activity against ABTS free radical with an IC50of 42.27μg/mL.Pearson’s correlation analysis indicated a strong negative correlation (r=-0.956) between DPPH radical scavenging activity (IC50) and the saponin content in the samples examined.In addition,the aqueous extract showed the best α-glucosidase inhibitory activity compared with other extracts.All the extracts had fair antibacterial activity against Bacillus subtilis,Escherichia coli,and Klebsiella pneumoniae except for the aqueous extract.Conclusions:Juglans regia extracts show potent antioxidant,antimicrobial,and α-glucosidase inhibitory activities.There is a correlation between saponin levels in Juglans regia leaf extracts and the studied activities.However,additional research is required to establish these relationships by identifying the specific saponin molecules responsible for these activities and elucidating their mechanisms of action.展开更多
The antiparacitic agent Flubendazole (F) caused a dose-dependent and time-dependent induction of polyploid in C3H1OT cells.At concentrations of 78ug/ml the yield of polyploidcells was 95%.Harringtonine(H),a antineopl...The antiparacitic agent Flubendazole (F) caused a dose-dependent and time-dependent induction of polyploid in C3H1OT cells.At concentrations of 78ug/ml the yield of polyploidcells was 95%.Harringtonine(H),a antineoplastic agent in-duced chromosome aberrations at 0.195ug/ml.Both F and H werecytotoxicity in the concentration ranges of 0.04-0.16ug/ml展开更多
Objective:To evaluate the efficacy of ponatinib plus gossypol against colorectal cancer HCT-116 and Caco-2 cells.Methods:Cells were treated with ponatinib and/or gossypol at increasing concentrations to evaluate syner...Objective:To evaluate the efficacy of ponatinib plus gossypol against colorectal cancer HCT-116 and Caco-2 cells.Methods:Cells were treated with ponatinib and/or gossypol at increasing concentrations to evaluate synergistic drug interactions by combination index.Cell viability,FGF19/FGFR4,and apoptotic and autophagic cell death were studied.Results:Ponatinib(1.25-40μM)and gossypol(2.5-80μM)monotherapy inhibited HCT-116 and Caco-2 cell viability in a doseand time-dependent manner.The combination of ponatinib and gossypol at a ratio of 1 to 2 significantly decreased cell viability(P<0.05),with a>2-and>4-fold reduction in IC50,respectively,after 24 h and 48 h,as compared to the IC50 of ponatinib.Lower combined concentrations showed greater synergism(combination index<1)with a higher ponatinib dose reduction index.Moreover,ponatinib plus gossypol induced morphological changes in HCT-116and Caco-2 cells,increased beclin-1 and caspase-3,and decreased FGF19,FGFR4,Bcl-2 and p-Akt as compared to treatment with drugs alone.Conclusions:Gossypol enhances ponatinib's anticancer effects against colorectal cancer cells through antiproliferative,apoptotic,and autophagic mechanisms.This may open the way for the future use of ponatinib at lower doses with gossypol as a potentially safer targeted strategy for colorectal cancer treatment.展开更多
Thenorphine is a new parrtail agonist of opioid recepter synthesized by our institute of pharmacology and toxicology.There are double effects of agonist and antegonist on opioid recepter. The agonist effect was showed...Thenorphine is a new parrtail agonist of opioid recepter synthesized by our institute of pharmacology and toxicology.There are double effects of agonist and antegonist on opioid recepter. The agonist effect was showed by analgesia. The analgesic properties are stronger efficacy (ED50 1 mg/kg po) ; longer duration (t1/2 9h) and lower dependence (no展开更多
The body of evidence investigating human epidermal growth factor receptor-2(HER2)directed therapy in patients with breast cancer(BC)has been growing within the last decade.Recently,the use of tyrosine kinase inhibitor...The body of evidence investigating human epidermal growth factor receptor-2(HER2)directed therapy in patients with breast cancer(BC)has been growing within the last decade.Recently,the use of tyrosine kinase inhibitors(TKIs)has been of particular interest in the treatment of human malignancies.This literature commentary is intended to highlight the most recent findings associated with the widely-studied TKI agents and their clinical significance in improving the outcomes of HER2 positive BC.展开更多
Objective:To evaluate the effectiveness and safety of ivermectin in patients with mild and moderate COVID-19.Methods:This study was a single-center,randomized,open-label,controlled trial with a 2-arm parallel-group de...Objective:To evaluate the effectiveness and safety of ivermectin in patients with mild and moderate COVID-19.Methods:This study was a single-center,randomized,open-label,controlled trial with a 2-arm parallel-group design on 68 patients with COVID-19.According to the 1:1 ratio between the study groups(ivermectin group and standard treatment group),patients were randomly admitted to each intervention arm.Results:The mean age of the participants in the ivermectin group was(48.37±13.32)years.Eighteen of them were males(54.5%)and the participants in the control group had a mean age of(46.28±14.47)years,with nineteen of them being males(59.4%).As a primary outcome,after 5 days of randomization,there was no significant difference between the ivermectin group and the control group in the length of stay in the hospital(P=0.168).ICU admission(P=0.764),length of stay in ICU(P=0.622),in-hospital mortality(P=0.427),adverse drug reactions,and changes in the mean difference of laboratory data had not any significant difference between the two groups(except for urea change).In addition,the radiologic findings of the two groups of patients were not significantly different.Linear regression analysis showed that for every 10 years increase of age,0.6 day of hospitalization duration was increased.There was no statistically significant association between other variables and clinical outcomes.Conclusions:Among adult hospitalized patients with moderate to severe COVID-19,there was no significant relationship between the administration of ivermectin single dose in a five-day course and clinical improvement,and mortality of the participants.展开更多
Objective:To evaluate the effect of hydroxysafflor yellow A(HSYA)on thioacetamide-induced liver fibrosis.Methods:Thioacetamide was administered to rats intraperitoneally in doses of 200 mg/kg twice a week for 12 weeks...Objective:To evaluate the effect of hydroxysafflor yellow A(HSYA)on thioacetamide-induced liver fibrosis.Methods:Thioacetamide was administered to rats intraperitoneally in doses of 200 mg/kg twice a week for 12 weeks.Thioacetamide-intoxicated rats were given silymarin(50 mg/kg)or HSYA(5 mg/kg)orally every day for 8 weeks.Liver enzymes,fibrosis markers,histological changes as well as immunohistochemistry of TNF-α,IL-6,p21,α-SMA,and caspase-3 were examined.The effect of HSYA on HSC-T6 activation/proliferation and apoptosis was also determined in vitro.Results:HSYA decreased liver enzymes,TNF-α,IL-6,and p21 expressions,hepatic PDGF-B,TIMP-1,TGF-β1,and hydroxyproline levels,as well as fibrosis score(S2 vs.S4)compared to the thioacetamide group.HSYA also downregulatedα-SMA while increasing caspase-3 expression.Surprisingly,at 500μg/mL,HSYA had only a slightly suppressive effect on HSC proliferation,with a 9.5%reduction.However,it significantly reduced TGF-β1,inhibitedα-SMA expression,induced caspase-3 expression,and promoted cell senescence.Conclusions:HSYA may be a potential therapeutic agent for delaying and reversing the progression of liver fibrosis.More research on HSYA at higher doses and for a longer period is warranted.展开更多
The synthesis of bile acids(BAs)is carried out by complex pathways characterized by sequential chemical reactions in the liver through various cytochromes P450(CYP)and other enzymes.Maintaining the integrity of these ...The synthesis of bile acids(BAs)is carried out by complex pathways characterized by sequential chemical reactions in the liver through various cytochromes P450(CYP)and other enzymes.Maintaining the integrity of these pathways is crucial for normal physiological function in mammals,encompassing hepatic and neurological processes.Studying on the deficiencies in BA synthesis genes offers valuable insights into the significance of BAs in modulating farnesoid X receptor(FXR)signaling and metabolic homeostasis.By creating mouse knockout(KO)models,researchers can manipulate deficiencies in genes involved in BA synthesis,which can be used to study human diseases with BA dysregulation.These KO mouse models allow for a more profound understanding of the functions and regulations of genes responsible for BA synthesis.Furthermore,KO mouse models shed light on the distinct characteristics of individual BA and their roles in nuclear receptor signaling.Notably,alterations of BA synthesis genes in mouse models have distinct differences when compared to human diseases caused by the same BA synthesis gene deficiencies.This review summarizes several mouse KO models used to study BA synthesis and related human diseases,including mice deficient in Cyp7a1,Cyp27a1,Cyp7a1/Cyp27a1,Cyp8b1,Cyp7b1,Cyp2c70,Cyp2a12,and Cyp2c70/Cyp2a12,as well as germ-free mice.展开更多
Liver disorders are one of the most common pathological problems worldwide.It affects more than 1.5 billion worldwide.Many types of hepatic cells have been reported to be involved in the initiation and propagation of ...Liver disorders are one of the most common pathological problems worldwide.It affects more than 1.5 billion worldwide.Many types of hepatic cells have been reported to be involved in the initiation and propagation of both acute and chronic liver diseases,including hepatocytes,Kupffer cells,sinusoidal endothelial cells,and hepatic stellate cells(HSCs).In addition,oxidative stress,cytokines,fibrogenic factors,microRNAs,and autophagy are also involved.Understanding the molecular mechanisms of liver diseases leads to discovering new therapeutic interventions that can be used in clinics.Recently,antioxidant,anti-inflammatory,anti-HSCs therapy,gene therapy,cell therapy,gut microbiota,and nanoparticles have great potential for preventing and treating liver diseases.Here,we explored the recent possible molecular mechanisms involved in the pathogenesis of acute and chronic liver diseases.Besides,we overviewed the recent therapeutic interventions that targeted liver diseases and summarized the recent studies concerning liver disorders therapy.展开更多
Though significant improvements have been made in the treatment methods for ovarian cancer(OC),the prognosis for OC patients is still poor.Exploring hub genes associated with the development of OC and utilizing them a...Though significant improvements have been made in the treatment methods for ovarian cancer(OC),the prognosis for OC patients is still poor.Exploring hub genes associated with the development of OC and utilizing them as appropriate potential biomarkers or therapeutic targets is highly valuable.In this study,the differentially expressed genes(DEGs)were identified from an independent GSE69428 Gene Expression Omnibus(GEO)dataset between OC and control samples.The DEGs were processed to construct the protein-protein interaction(PPI)network using STRING.Later,hub genes were identified through Cytohubba analysis of the Cytoscape.Expression and survival profiling of the hub genes were validated using GEPIA,OncoDB,and GENT2.For exploring promoter methylation levels and genetic alterations in hub genes,MEXPRESS and cBioPortal were utilized,respectively.Moreover,DAVID,HPA,TIMER,CancerSEA,ENCORI,DrugBank,and GSCAlite were used for gene enrichment analysis,subcellular localization analysis,immune cell infiltration analysis,exploring correlations between hub genes and different diverse states,lncRNA-miRNA-mRNA co-regulatory network analysis,predicting hub gene-associated drugs,and conducting drug sensitivity analysis,respectively.In total,8947 DEGs were found between OC and normal samples in GSE69428.After STRING and Cytohubba analysis,4 hub genes including TTK(TTK Protein Kinase),(BUB1 mitotic checkpoint serine/threonine kinase B)BUB1B,(Nucleolar and spindle-associated protein 1)NUSAP1,and(ZW10 interacting kinetochore protein)ZWINT were selected as the hub genes.Further,it was validated that these 4 hub genes were significantly up-regulated in OC samples compared to normal controls,but overexpression of these genes was not associated with overall survival(OS).However,genetic alterations in those genes were found to be linked with OS and disease-free(DFS)survival.Moreover,this study also revealed some novel links between TTK,BUB1B,NUSAP1,and ZWINT overexpression and promoter methylation status,immune cell infiltration,miRNAs,gene enrichment terms,and various chemotherapeutic drugs.Four hub genes,including TTK,BUB1B,NUSAP1,and ZWINT,were revealed as tumor-promotive factors in OC,having the potential to be utilized as novel biomarkers and therapeutic targets for OC management.展开更多
The coronavirus disease 2019(COVID-19)pandemic caused by frequently mutating severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has had a worldwide impact.However,detailed data on the potential aerosol transmi...The coronavirus disease 2019(COVID-19)pandemic caused by frequently mutating severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has had a worldwide impact.However,detailed data on the potential aerosol transmission of SARS-CoV-2 in real-world and controlled laboratory settings remain sparse.During the COVID-19 pandemic in Shanghai,China in 2022,samples were collected in a Fangcang shelter hospital,a large-scale temporary hospital rapidly built by converting the existing National Exhibition and Convention Center(Shanghai)into a health care facility.Aerosol samples at different sites and intervals around patients and in public areas,surface samples,and pharyngeal swab samples from corresponding patients were included.Samples were tested for SARS-CoV-2 using real-time quantitative polymerase chain reaction(RT-qPCR)assays,followed by sequencing if the cycle threshold(Ct)value was<30.The positivity rate for SARS-CoV-2 in aerosol samples was high in contaminated zones(37.5%,104/277),especially around the bed(41.2%,68/165)and near ventilation inlets(45.2%,14/31).The prevalence of SARS-CoV-2 around the bed,public areas,and air inlets of exhaust vents fluctuated and was closely related to the positivity rate among patients at corresponding sampling sites.Some surface samples of different personal protective equipment from medical staff had high positivity rates.Sixty sequences of joined ORF1ab and spike genes obtained from sixty samples represented two main clusters of Omicron SARS-CoV-2.There was consistency in virus sequences from the same patient and their environment,and the detected virus sequences matched those of virus strains in circulation during the collection periods,which indicated a high likelihood of cross-contamination in the Fangcang shelter hospital.In summary,the results provide a quantitative and real landscape of the aerosol transmission of SARS-CoV-2 and a patient-centered view of contamination in large and enclosed spaces and offer a useful guide for taking targeted measures to avoid nosocomial infections during the management of SARS-CoV-2 or other respiratory virus diseases in a Fangcang shelter hospital.展开更多
Codiaeum variegatum has been widely investigated for its biological proprieties ranging from the antiamoebic potential to the phytochemical analysis. The aim of the present study was to evaluate the anti-inflammatory ...Codiaeum variegatum has been widely investigated for its biological proprieties ranging from the antiamoebic potential to the phytochemical analysis. The aim of the present study was to evaluate the anti-inflammatory potential of C. variegatum leaf extracts and fractions. A primary macrophage culture activated by Saccharomyces cereviseae (SC) was used to evaluate cell cytotoxicity and anti-inflammatory potential of the plant extracts and fractions. Macrophages were treated with different concentrations (0.1;1;10 and 100 μg/mL) of the extracts/fractions for the inhibition of 5-lipoxygenase activity, nitric oxide (NO) and Tumor Necrosis Factor Alpha (TNF-α) production. No significant difference was observed on cell viability in the presence of extracts and fractions at tested concentration during the incubation period. Extracts and fractions of C. variegatum inhibited the 5-lipoxygenase activity, NO and TNF-α production by viable primary mouse macrophages in a concentration-dependent manner. The fractionation process increased anti-inflammatory activity. Among fractions, HEF2, HEF3, HEF5, EEF1, EEF3 and EEF5 exhibited the best anti-inflammatory potential. C. variegatum extracts and fractions exhibited a greater anti-inflammatory potential throughout the inhibition of pro-inflammatory mediators such as NO, 5-Lox and TNF-α.展开更多
Amoebiasis, classified as the third intestinal parasitic infection, represents a public health problem in low-income countries where hygiene and sanitation conditions are poor. With the resurgence of resistant pathoge...Amoebiasis, classified as the third intestinal parasitic infection, represents a public health problem in low-income countries where hygiene and sanitation conditions are poor. With the resurgence of resistant pathogenic strains as well as ancestral considerations in developing countries such as Cameroon, many people rely on medicinal plants to treat a plethora of diseases. This work aimed to highlight the anti-amoebic and anti-oxidant potential of Codiaeum variegatum extracts and fractions. The anti-amoebic potential of C. variegatum was assayed on the polyxenic culture of the clinical isolates of E. histolytica. Then, the anti-oxidant potential of the ethanolic/hydroethanolic extracts and fractions was evaluated through DPPH radical scavenging, iron reduction (FRAP), lipid peroxidation inhibitory potential and total antioxidant capacity tests followed by the determination of phenolic compound and flavonoid content. It was found that the fractionation process decreased the amoebicidal activities of C. variegatum leaf extracts. However hydroethanolic extract (CI<sub>50</sub>: 10.08 ± 0.42, 5.18 ± 0.09, 5.18 ± 0.09 μg/mL respectively after 24, 48 and 72 hours) was more active than ethanolic extract (CI<sub>50</sub>: 15.59 ± 6.17;9.61 ± 2.37;6.26 ± 3.22 μg/mL respectively after 24, 48 and 72 hours). Interestingly, the activities of hydroethanolic extract were significantly non-different compared to metronidazole CI<sub>50</sub>: 8.42 ± 0.44, 6.45 ± 0.22 and 3.42 ± 0.33 μg/mL, respectively after 24, 48 and 72 hours). Ethanolic extract and EF5 showed higher Phenolic compound contents and higher antioxidant activity than hydroethanolic extract and other fractions through DPPH radical scavenging power (EC50 = 311.50 ± 4.12 μg/mL) and total antioxidant capacity (44 ± 0.07 mgEAA/gF). However, these activities are significantly lower than those of ascorbic acid (EC50 = 31.20 ± 4.39 μg/mL, and 61.34 ± 4.42 μg/mL respectively). This low antioxidant activity was confirmed by poor phenolic and flavonoid compounds contents found in the extracts and fractions. The present result brings a new approach to the ethnopharmacological uses of C. variegatum against dysentery in cases associated with Amoebiasis in Cameroun.展开更多
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 ...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.展开更多
The low survival rate of Kidney renal clear cell carcinoma(KIRC)patients is largely attributed to cisplatin resistance.Rather than focusing solely on individual proteins,exploring protein-protein interactions could of...The low survival rate of Kidney renal clear cell carcinoma(KIRC)patients is largely attributed to cisplatin resistance.Rather than focusing solely on individual proteins,exploring protein-protein interactions could offer greater insight into drug resistance.To this end,a series of in silico and in vitro experiments were conducted to identify hub genes in the intricate network of cisplatin resistance-related genes in KIRC chemotherapy.The genes involved in cisplatin resistance across KIRC were retrieved from the National Center for Biotechnology Information(NCBI)database using search terms as“Kidney renal clear cell carcinoma”and“Cisplatin resistance”.The genes retrieved were analyzed for hub gene identification using the STRING database and Cytoscape tool.Expression and promoter methylation profiling of the hub genes was done using UALCAN,GEPIA,OncoDB,and HPA databases.Mutational,survival,functional enrichment,immune cell infiltration,and drug prediction analyses of the hub genes were performed using the cBioPortal,GEPIA,GSEA,TIMER,and DrugBank databases.Lastly,expression and methylation levels of the hub genes were validated on two cisplatin-resistant RCC cell lines(786-O and A-498)and a normal renal tubular epithelial cell line(HK-2)using two high throughput techniques,including targeted bisulfite sequencing(bisulfite-seq)and RT-qPCR.A total of 124 genes were identified as being associated with cisplatin resistance in KIRC.Out of these genes,MCL1,IGF1R,CCND1,and PTEN were identified as hub genes and were found to have significant(p<0.05)variations in their mRNA and protein expressions and effects on the overall survival(OS)of the KIRC patients.Moreover,an aberrant promoter methylation pattern was found to be associated with the dysregulation of the hub genes.In addition to this,hub genes were also linked with different cisplatin resistance-causing pathways.Thus,hub genes can be targeted with Alvocidib,Estradiol,Tretinoin,Capsaicin,Dronabinol,Metribolone,Calcitriol,Acetaminophen,Acitretin,Cyclosporine,Azacitidine,Genistein,and Resveratrol drugs.As the pathogenesis of KIRC is complex,targeting hub genes and associated pathways involved in cisplatin resistance could bring a milestone change in the drug discovery and management of drug resistance,which might uplift overall survival among KIRC patients.展开更多
The Rat sarcoma virus (RAS) family of proteins, which includes the Kristen Rat sarcoma virus (KRAS), is linked to nearly one-fourth of all human cancers. KRAS mutations, in particular, are associated with Non-Small Ce...The Rat sarcoma virus (RAS) family of proteins, which includes the Kristen Rat sarcoma virus (KRAS), is linked to nearly one-fourth of all human cancers. KRAS mutations, in particular, are associated with Non-Small Cell Lung Carcinoma (NSCLC), colorectal cancer, adenocarcinomas, ovarian carcinoma, and endometrial tumors. KRAS activates 80 different signaling pathways, including Mitogen-activated protein kinases (MAPK) and Phosphoinositide 3-kinase (PI3K), and up-regulates transcription factors such as ETS like Protein (ELK), Jun Proto-Oncogene (JUN), and Myelocytomatosis (MYC), which are involved in cell differentiation, proliferation, transformation, and survival. KRAS mutations are also known to cause autocrine function, which further exacerbates the situation. In NSCLC, KRAS mutations have a strong positive correlation with the disease, particularly in patients with a smoking history. In pancreatic cancer, KRAS mutations are a dominant pathological basis, with most mutations being G12D, G12V, G13D, G13C, G13S, and G13R. These mutations serve as initial markers in tumorigenesis and are associated with poor prognosis and high mortality rates. In colorectal cancer, KRAS mutations contribute to 4/5 of cases, with cellular mechanisms involving the MAPK pathway, which resists anti-epidermal growth factor antibodies. In Low-grade Serous Ovarian Cancer (LGSOC), KRAS mutations are associated with altered signaling in the MAPK pathway and drug resistance. However, treatments such as Selumetinib, a down regulator of RAS/Rapidly Accelerated Fibrosarcoma (RAF)/Mitogen-activated protein kinase (MEK) pathways, and a combination of trametinib and buparlisib have shown promise in managing LGSOC when diagnosed early through KRAS mutation markers. Although KRAS mutations are commonly associated with many types of cancer, their use in clinical practice is limited due to the lack of accurate methods to identify them. It is needed to further isolate the KRAS mutation products and correlate the cancer-causing genes to make it a promising approach for cancer chemotherapy.展开更多
基金financially supported by postdoctoral funding of Hebei Medical UniversityHebei Province Postdoctoral Research Project Funding(B2022003035)+5 种基金Natural Science Foundation of Hebei Province(H2020206579)CAMS Innovation Found for Medical Sciences(2019-I2M-5-055)2023 Scientific Research Projects of Colleges and Universities in Hebei Province(QN2023131)S&T Program of Hebei(18277743D)Undergraduate Innovation Experiment Project from Hebei Medical University(USIP2019008)Spring rain project of Hebei Medical University(CYCZ201906)。
文摘Human normal flora is a source of probiotics.The safety characteristics of a specific isolate determine its application in foods or drugs.The food-borne-pathogen antagonist strain Lactobacillus gasseri HMV18 is one of the isolates from normal human flora.In this work,we assessed the in vitro pH tolerance,bile tolerance,biogenic amine production,mucin utilization,and safety of in vivo administration to mice to evaluate general health,organ-body weight index,organ histopathological change,whether L.gasseri HMV18 can colonize in the gut or modulate the gut microbiota after oral administration.The results suggest that L.gasseri HMV18 can tolerate pH 3 for 2 h,3%bile for 3 h,biogenic amine negative,mucin usage negative,does not encode verified toxins,and cause no visible change in mice's organs.L.gasseri HMV18 might not colonize in mice's gut,but can significantly affect the structure of gut microbiota.A bibliographical survey suggested that there were as few as 8 opportunistic infection cases from 1984 to 2022 and that the possibility for L.gasseri to cause infection is relatively low.Therefore,this work provides a basis for the foods or drugs application of L.gasseri HMV18 and gives a map of experiments for the safety assessment of probiotics.
文摘Patients and physicians understand the importance of self-care following spinal cord injury (SCI), yet many individuals with SCI do not adhere to recommended self-care activities despite logistical supports. Neurobehavioral determinants of SCI self-care behavior, such as impulsivity, are not widely studied, yet understanding them could inform efforts to improve SCI self-care. We explored associations between impulsivity and self-care in an observational study of 35 US adults age 18 - 50 who had traumatic SCI with paraplegia at least six months before assessment. The primary outcome measure was self-reported self-care. In LASSO regression models that included all neurobehavioral measures and demographics as predictors of self-care, dispositional measures of greater impulsivity (negative urgency, lack of premeditation, lack of perseverance), and reduced mindfulness were associated with reduced self-care. Outcome (magnitude) sensitivity, a latent decision-making parameter derived from computationally modeling successive choices in a gambling task, was also associated with self-care behavior. These results are preliminary;more research is needed to demonstrate the utility of these findings in clinical settings. Information about associations between impulsivity and poor self-care in people with SCI could guide the development of interventions to improve SCI self-care and help patients with elevated risks related to self-care and secondary health conditions.
文摘The coronavirus disease 2019(COVID-19)represents a global health and economic challenge.Hepatic injuries have been approved to be associated with severe acute respiratory syndrome coronavirus(SARS-CoV-2)infection.The viral tropism pattern of SARS-CoV-2 can induce hepatic injuries either by itself or by worsening the conditions of patients with hepatic diseases.Besides,other factors have been reported to play a crucial role in the pathological forms of hepatic injuries induced by SARS-CoV-2,including cytokine storm,hypoxia,endothelial cells,and even some treatments for COVID-19.On the other hand,several groups of people could be at risk of hepatic COVID-19 complications,such as pregnant women and neonates.The present review outlines and discusses the interplay between SARS-CoV-2 infection and hepatic injury,hepatic illness comorbidity,and risk factors.Besides,it is focused on the vaccination process and the role of developed vac-cines in preventing hepatic injuries due to SARS-CoV-2 infection.
基金supported by National Natural Science Foundation of China [No. 81773405 to Y.Q. and No. 82173644to X.Y.]Shanxi Natural Science Foundation of China [No.202203021211246 and No. 202103021224242]。
文摘Objective Arsenic(As) and fluoride(F) are two of the most common elements contaminating groundwater resources. A growing number of studies have found that As and F can cause neurotoxicity in infants and children, leading to cognitive, learning, and memory impairments. However, early biomarkers of learning and memory impairment induced by As and/or F remain unclear. In the present study, the mechanisms by which As and/or F cause learning memory impairment are explored at the multi-omics level(microbiome and metabolome).Methods We stablished an SD rats model exposed to arsenic and/or fluoride from intrauterine to adult period.Results Arsenic and/fluoride exposed groups showed reduced neurobehavioral performance and lesions in the hippocampal CA1 region. 16S rRNA gene sequencing revealed that As and/or F exposure significantly altered the composition and diversity of the gut microbiome, featuring the Lachnospiraceae_NK4A136_group, Ruminococcus_1, Prevotellaceae_NK3B31_group, [Eubacterium]_xylanophilum_group. Metabolome analysis showed that As and/or F-induced learning and memory impairment may be related to tryptophan, lipoic acid, glutamate, gamma-aminobutyric acidergic(GABAergic) synapse, and arachidonic acid(AA) metabolism. The gut microbiota, metabolites, and learning memory indicators were significantly correlated.Conclusion Learning memory impairment triggered by As and/or F exposure may be mediated by different gut microbes and their associated metabolites.
基金supported by the Deanship of Scientific Research at Umm Al-Qura University(Grant code:22UQU4331128DSR77).
文摘Objective:To investigate the relationship between triterpenoid saponin content and antioxidant,antimicrobial,and α-glucosidase inhibitory activities of 70%ethanolic,butanolic,aqueous,supernate and precipitate extracts of Juglans regia leaves.Methods:Triterpenoid saponins of different Juglans regia leaf extracts were measured by the vanillin method.Antioxidant activity was evaluated against DPPH and ABTS free radicals.We also assessed α-glucosidase inhibitory and antimicrobial activities of the leaf extracts.Pearson’s correlation coefficient was evaluated to determine the correlation between the saponin content and biological activities.Results:The butanolic extract was most effective against DPPH with an IC50of 6.63μg/mL,while the aqueous extract showed the highest scavenging activity against ABTS free radical with an IC50of 42.27μg/mL.Pearson’s correlation analysis indicated a strong negative correlation (r=-0.956) between DPPH radical scavenging activity (IC50) and the saponin content in the samples examined.In addition,the aqueous extract showed the best α-glucosidase inhibitory activity compared with other extracts.All the extracts had fair antibacterial activity against Bacillus subtilis,Escherichia coli,and Klebsiella pneumoniae except for the aqueous extract.Conclusions:Juglans regia extracts show potent antioxidant,antimicrobial,and α-glucosidase inhibitory activities.There is a correlation between saponin levels in Juglans regia leaf extracts and the studied activities.However,additional research is required to establish these relationships by identifying the specific saponin molecules responsible for these activities and elucidating their mechanisms of action.
文摘The antiparacitic agent Flubendazole (F) caused a dose-dependent and time-dependent induction of polyploid in C3H1OT cells.At concentrations of 78ug/ml the yield of polyploidcells was 95%.Harringtonine(H),a antineoplastic agent in-duced chromosome aberrations at 0.195ug/ml.Both F and H werecytotoxicity in the concentration ranges of 0.04-0.16ug/ml
基金financial support from the Theodor Bilharz Research InstituteWarrak El-Hadar+1 种基金ImbabaGiza 12411,Egypt。
文摘Objective:To evaluate the efficacy of ponatinib plus gossypol against colorectal cancer HCT-116 and Caco-2 cells.Methods:Cells were treated with ponatinib and/or gossypol at increasing concentrations to evaluate synergistic drug interactions by combination index.Cell viability,FGF19/FGFR4,and apoptotic and autophagic cell death were studied.Results:Ponatinib(1.25-40μM)and gossypol(2.5-80μM)monotherapy inhibited HCT-116 and Caco-2 cell viability in a doseand time-dependent manner.The combination of ponatinib and gossypol at a ratio of 1 to 2 significantly decreased cell viability(P<0.05),with a>2-and>4-fold reduction in IC50,respectively,after 24 h and 48 h,as compared to the IC50 of ponatinib.Lower combined concentrations showed greater synergism(combination index<1)with a higher ponatinib dose reduction index.Moreover,ponatinib plus gossypol induced morphological changes in HCT-116and Caco-2 cells,increased beclin-1 and caspase-3,and decreased FGF19,FGFR4,Bcl-2 and p-Akt as compared to treatment with drugs alone.Conclusions:Gossypol enhances ponatinib's anticancer effects against colorectal cancer cells through antiproliferative,apoptotic,and autophagic mechanisms.This may open the way for the future use of ponatinib at lower doses with gossypol as a potentially safer targeted strategy for colorectal cancer treatment.
文摘Thenorphine is a new parrtail agonist of opioid recepter synthesized by our institute of pharmacology and toxicology.There are double effects of agonist and antegonist on opioid recepter. The agonist effect was showed by analgesia. The analgesic properties are stronger efficacy (ED50 1 mg/kg po) ; longer duration (t1/2 9h) and lower dependence (no
基金Supported by the Elsa U.Pardee Foundation Grant,No.671432(to Sahu RP)NIH R21 Grant,No.ES033806(to Sahu RP).
文摘The body of evidence investigating human epidermal growth factor receptor-2(HER2)directed therapy in patients with breast cancer(BC)has been growing within the last decade.Recently,the use of tyrosine kinase inhibitors(TKIs)has been of particular interest in the treatment of human malignancies.This literature commentary is intended to highlight the most recent findings associated with the widely-studied TKI agents and their clinical significance in improving the outcomes of HER2 positive BC.
基金Hormozgan University of Medical Sciences,Bandar Abbas,Iran(grant No.990238)。
文摘Objective:To evaluate the effectiveness and safety of ivermectin in patients with mild and moderate COVID-19.Methods:This study was a single-center,randomized,open-label,controlled trial with a 2-arm parallel-group design on 68 patients with COVID-19.According to the 1:1 ratio between the study groups(ivermectin group and standard treatment group),patients were randomly admitted to each intervention arm.Results:The mean age of the participants in the ivermectin group was(48.37±13.32)years.Eighteen of them were males(54.5%)and the participants in the control group had a mean age of(46.28±14.47)years,with nineteen of them being males(59.4%).As a primary outcome,after 5 days of randomization,there was no significant difference between the ivermectin group and the control group in the length of stay in the hospital(P=0.168).ICU admission(P=0.764),length of stay in ICU(P=0.622),in-hospital mortality(P=0.427),adverse drug reactions,and changes in the mean difference of laboratory data had not any significant difference between the two groups(except for urea change).In addition,the radiologic findings of the two groups of patients were not significantly different.Linear regression analysis showed that for every 10 years increase of age,0.6 day of hospitalization duration was increased.There was no statistically significant association between other variables and clinical outcomes.Conclusions:Among adult hospitalized patients with moderate to severe COVID-19,there was no significant relationship between the administration of ivermectin single dose in a five-day course and clinical improvement,and mortality of the participants.
基金funded by Theodore Bilharz Research Institute (grant number:ID-MS-99/A,Principal investigator:Naglaa M.El-Lakkany).
文摘Objective:To evaluate the effect of hydroxysafflor yellow A(HSYA)on thioacetamide-induced liver fibrosis.Methods:Thioacetamide was administered to rats intraperitoneally in doses of 200 mg/kg twice a week for 12 weeks.Thioacetamide-intoxicated rats were given silymarin(50 mg/kg)or HSYA(5 mg/kg)orally every day for 8 weeks.Liver enzymes,fibrosis markers,histological changes as well as immunohistochemistry of TNF-α,IL-6,p21,α-SMA,and caspase-3 were examined.The effect of HSYA on HSC-T6 activation/proliferation and apoptosis was also determined in vitro.Results:HSYA decreased liver enzymes,TNF-α,IL-6,and p21 expressions,hepatic PDGF-B,TIMP-1,TGF-β1,and hydroxyproline levels,as well as fibrosis score(S2 vs.S4)compared to the thioacetamide group.HSYA also downregulatedα-SMA while increasing caspase-3 expression.Surprisingly,at 500μg/mL,HSYA had only a slightly suppressive effect on HSC proliferation,with a 9.5%reduction.However,it significantly reduced TGF-β1,inhibitedα-SMA expression,induced caspase-3 expression,and promoted cell senescence.Conclusions:HSYA may be a potential therapeutic agent for delaying and reversing the progression of liver fibrosis.More research on HSYA at higher doses and for a longer period is warranted.
基金This study was supported by grants from National Institutes of Health(GM135258,GM093854)the Department of Veteran Affairs(BX002741)the Rutgers NIEHS Center for Environmental Expo-sure and Diseases(CEED)(P30 ES005022).
文摘The synthesis of bile acids(BAs)is carried out by complex pathways characterized by sequential chemical reactions in the liver through various cytochromes P450(CYP)and other enzymes.Maintaining the integrity of these pathways is crucial for normal physiological function in mammals,encompassing hepatic and neurological processes.Studying on the deficiencies in BA synthesis genes offers valuable insights into the significance of BAs in modulating farnesoid X receptor(FXR)signaling and metabolic homeostasis.By creating mouse knockout(KO)models,researchers can manipulate deficiencies in genes involved in BA synthesis,which can be used to study human diseases with BA dysregulation.These KO mouse models allow for a more profound understanding of the functions and regulations of genes responsible for BA synthesis.Furthermore,KO mouse models shed light on the distinct characteristics of individual BA and their roles in nuclear receptor signaling.Notably,alterations of BA synthesis genes in mouse models have distinct differences when compared to human diseases caused by the same BA synthesis gene deficiencies.This review summarizes several mouse KO models used to study BA synthesis and related human diseases,including mice deficient in Cyp7a1,Cyp27a1,Cyp7a1/Cyp27a1,Cyp8b1,Cyp7b1,Cyp2c70,Cyp2a12,and Cyp2c70/Cyp2a12,as well as germ-free mice.
文摘Liver disorders are one of the most common pathological problems worldwide.It affects more than 1.5 billion worldwide.Many types of hepatic cells have been reported to be involved in the initiation and propagation of both acute and chronic liver diseases,including hepatocytes,Kupffer cells,sinusoidal endothelial cells,and hepatic stellate cells(HSCs).In addition,oxidative stress,cytokines,fibrogenic factors,microRNAs,and autophagy are also involved.Understanding the molecular mechanisms of liver diseases leads to discovering new therapeutic interventions that can be used in clinics.Recently,antioxidant,anti-inflammatory,anti-HSCs therapy,gene therapy,cell therapy,gut microbiota,and nanoparticles have great potential for preventing and treating liver diseases.Here,we explored the recent possible molecular mechanisms involved in the pathogenesis of acute and chronic liver diseases.Besides,we overviewed the recent therapeutic interventions that targeted liver diseases and summarized the recent studies concerning liver disorders therapy.
基金Researchers Supporting Project Number(RSPD2023R725)King Saud University,Riyadh,Saudi Arabia.
文摘Though significant improvements have been made in the treatment methods for ovarian cancer(OC),the prognosis for OC patients is still poor.Exploring hub genes associated with the development of OC and utilizing them as appropriate potential biomarkers or therapeutic targets is highly valuable.In this study,the differentially expressed genes(DEGs)were identified from an independent GSE69428 Gene Expression Omnibus(GEO)dataset between OC and control samples.The DEGs were processed to construct the protein-protein interaction(PPI)network using STRING.Later,hub genes were identified through Cytohubba analysis of the Cytoscape.Expression and survival profiling of the hub genes were validated using GEPIA,OncoDB,and GENT2.For exploring promoter methylation levels and genetic alterations in hub genes,MEXPRESS and cBioPortal were utilized,respectively.Moreover,DAVID,HPA,TIMER,CancerSEA,ENCORI,DrugBank,and GSCAlite were used for gene enrichment analysis,subcellular localization analysis,immune cell infiltration analysis,exploring correlations between hub genes and different diverse states,lncRNA-miRNA-mRNA co-regulatory network analysis,predicting hub gene-associated drugs,and conducting drug sensitivity analysis,respectively.In total,8947 DEGs were found between OC and normal samples in GSE69428.After STRING and Cytohubba analysis,4 hub genes including TTK(TTK Protein Kinase),(BUB1 mitotic checkpoint serine/threonine kinase B)BUB1B,(Nucleolar and spindle-associated protein 1)NUSAP1,and(ZW10 interacting kinetochore protein)ZWINT were selected as the hub genes.Further,it was validated that these 4 hub genes were significantly up-regulated in OC samples compared to normal controls,but overexpression of these genes was not associated with overall survival(OS).However,genetic alterations in those genes were found to be linked with OS and disease-free(DFS)survival.Moreover,this study also revealed some novel links between TTK,BUB1B,NUSAP1,and ZWINT overexpression and promoter methylation status,immune cell infiltration,miRNAs,gene enrichment terms,and various chemotherapeutic drugs.Four hub genes,including TTK,BUB1B,NUSAP1,and ZWINT,were revealed as tumor-promotive factors in OC,having the potential to be utilized as novel biomarkers and therapeutic targets for OC management.
基金supported by National Key Research and Development Program of China(2019YFC1200500)supported by Emergency Key Program of Guangzhou Laboratory(EKPG21-01)supported by National Natural Science Foundation of China(32070166)。
文摘The coronavirus disease 2019(COVID-19)pandemic caused by frequently mutating severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has had a worldwide impact.However,detailed data on the potential aerosol transmission of SARS-CoV-2 in real-world and controlled laboratory settings remain sparse.During the COVID-19 pandemic in Shanghai,China in 2022,samples were collected in a Fangcang shelter hospital,a large-scale temporary hospital rapidly built by converting the existing National Exhibition and Convention Center(Shanghai)into a health care facility.Aerosol samples at different sites and intervals around patients and in public areas,surface samples,and pharyngeal swab samples from corresponding patients were included.Samples were tested for SARS-CoV-2 using real-time quantitative polymerase chain reaction(RT-qPCR)assays,followed by sequencing if the cycle threshold(Ct)value was<30.The positivity rate for SARS-CoV-2 in aerosol samples was high in contaminated zones(37.5%,104/277),especially around the bed(41.2%,68/165)and near ventilation inlets(45.2%,14/31).The prevalence of SARS-CoV-2 around the bed,public areas,and air inlets of exhaust vents fluctuated and was closely related to the positivity rate among patients at corresponding sampling sites.Some surface samples of different personal protective equipment from medical staff had high positivity rates.Sixty sequences of joined ORF1ab and spike genes obtained from sixty samples represented two main clusters of Omicron SARS-CoV-2.There was consistency in virus sequences from the same patient and their environment,and the detected virus sequences matched those of virus strains in circulation during the collection periods,which indicated a high likelihood of cross-contamination in the Fangcang shelter hospital.In summary,the results provide a quantitative and real landscape of the aerosol transmission of SARS-CoV-2 and a patient-centered view of contamination in large and enclosed spaces and offer a useful guide for taking targeted measures to avoid nosocomial infections during the management of SARS-CoV-2 or other respiratory virus diseases in a Fangcang shelter hospital.
文摘Codiaeum variegatum has been widely investigated for its biological proprieties ranging from the antiamoebic potential to the phytochemical analysis. The aim of the present study was to evaluate the anti-inflammatory potential of C. variegatum leaf extracts and fractions. A primary macrophage culture activated by Saccharomyces cereviseae (SC) was used to evaluate cell cytotoxicity and anti-inflammatory potential of the plant extracts and fractions. Macrophages were treated with different concentrations (0.1;1;10 and 100 μg/mL) of the extracts/fractions for the inhibition of 5-lipoxygenase activity, nitric oxide (NO) and Tumor Necrosis Factor Alpha (TNF-α) production. No significant difference was observed on cell viability in the presence of extracts and fractions at tested concentration during the incubation period. Extracts and fractions of C. variegatum inhibited the 5-lipoxygenase activity, NO and TNF-α production by viable primary mouse macrophages in a concentration-dependent manner. The fractionation process increased anti-inflammatory activity. Among fractions, HEF2, HEF3, HEF5, EEF1, EEF3 and EEF5 exhibited the best anti-inflammatory potential. C. variegatum extracts and fractions exhibited a greater anti-inflammatory potential throughout the inhibition of pro-inflammatory mediators such as NO, 5-Lox and TNF-α.
文摘Amoebiasis, classified as the third intestinal parasitic infection, represents a public health problem in low-income countries where hygiene and sanitation conditions are poor. With the resurgence of resistant pathogenic strains as well as ancestral considerations in developing countries such as Cameroon, many people rely on medicinal plants to treat a plethora of diseases. This work aimed to highlight the anti-amoebic and anti-oxidant potential of Codiaeum variegatum extracts and fractions. The anti-amoebic potential of C. variegatum was assayed on the polyxenic culture of the clinical isolates of E. histolytica. Then, the anti-oxidant potential of the ethanolic/hydroethanolic extracts and fractions was evaluated through DPPH radical scavenging, iron reduction (FRAP), lipid peroxidation inhibitory potential and total antioxidant capacity tests followed by the determination of phenolic compound and flavonoid content. It was found that the fractionation process decreased the amoebicidal activities of C. variegatum leaf extracts. However hydroethanolic extract (CI<sub>50</sub>: 10.08 ± 0.42, 5.18 ± 0.09, 5.18 ± 0.09 μg/mL respectively after 24, 48 and 72 hours) was more active than ethanolic extract (CI<sub>50</sub>: 15.59 ± 6.17;9.61 ± 2.37;6.26 ± 3.22 μg/mL respectively after 24, 48 and 72 hours). Interestingly, the activities of hydroethanolic extract were significantly non-different compared to metronidazole CI<sub>50</sub>: 8.42 ± 0.44, 6.45 ± 0.22 and 3.42 ± 0.33 μg/mL, respectively after 24, 48 and 72 hours). Ethanolic extract and EF5 showed higher Phenolic compound contents and higher antioxidant activity than hydroethanolic extract and other fractions through DPPH radical scavenging power (EC50 = 311.50 ± 4.12 μg/mL) and total antioxidant capacity (44 ± 0.07 mgEAA/gF). However, these activities are significantly lower than those of ascorbic acid (EC50 = 31.20 ± 4.39 μg/mL, and 61.34 ± 4.42 μg/mL respectively). This low antioxidant activity was confirmed by poor phenolic and flavonoid compounds contents found in the extracts and fractions. The present result brings a new approach to the ethnopharmacological uses of C. variegatum against dysentery in cases associated with Amoebiasis in Cameroun.
文摘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.
基金The authors would like to extend their sincere appreciation to the Researchers Supporting Project Number(RSPD2023R986)King Saud University,Riyadh,Saudi Arabia.
文摘The low survival rate of Kidney renal clear cell carcinoma(KIRC)patients is largely attributed to cisplatin resistance.Rather than focusing solely on individual proteins,exploring protein-protein interactions could offer greater insight into drug resistance.To this end,a series of in silico and in vitro experiments were conducted to identify hub genes in the intricate network of cisplatin resistance-related genes in KIRC chemotherapy.The genes involved in cisplatin resistance across KIRC were retrieved from the National Center for Biotechnology Information(NCBI)database using search terms as“Kidney renal clear cell carcinoma”and“Cisplatin resistance”.The genes retrieved were analyzed for hub gene identification using the STRING database and Cytoscape tool.Expression and promoter methylation profiling of the hub genes was done using UALCAN,GEPIA,OncoDB,and HPA databases.Mutational,survival,functional enrichment,immune cell infiltration,and drug prediction analyses of the hub genes were performed using the cBioPortal,GEPIA,GSEA,TIMER,and DrugBank databases.Lastly,expression and methylation levels of the hub genes were validated on two cisplatin-resistant RCC cell lines(786-O and A-498)and a normal renal tubular epithelial cell line(HK-2)using two high throughput techniques,including targeted bisulfite sequencing(bisulfite-seq)and RT-qPCR.A total of 124 genes were identified as being associated with cisplatin resistance in KIRC.Out of these genes,MCL1,IGF1R,CCND1,and PTEN were identified as hub genes and were found to have significant(p<0.05)variations in their mRNA and protein expressions and effects on the overall survival(OS)of the KIRC patients.Moreover,an aberrant promoter methylation pattern was found to be associated with the dysregulation of the hub genes.In addition to this,hub genes were also linked with different cisplatin resistance-causing pathways.Thus,hub genes can be targeted with Alvocidib,Estradiol,Tretinoin,Capsaicin,Dronabinol,Metribolone,Calcitriol,Acetaminophen,Acitretin,Cyclosporine,Azacitidine,Genistein,and Resveratrol drugs.As the pathogenesis of KIRC is complex,targeting hub genes and associated pathways involved in cisplatin resistance could bring a milestone change in the drug discovery and management of drug resistance,which might uplift overall survival among KIRC patients.
文摘The Rat sarcoma virus (RAS) family of proteins, which includes the Kristen Rat sarcoma virus (KRAS), is linked to nearly one-fourth of all human cancers. KRAS mutations, in particular, are associated with Non-Small Cell Lung Carcinoma (NSCLC), colorectal cancer, adenocarcinomas, ovarian carcinoma, and endometrial tumors. KRAS activates 80 different signaling pathways, including Mitogen-activated protein kinases (MAPK) and Phosphoinositide 3-kinase (PI3K), and up-regulates transcription factors such as ETS like Protein (ELK), Jun Proto-Oncogene (JUN), and Myelocytomatosis (MYC), which are involved in cell differentiation, proliferation, transformation, and survival. KRAS mutations are also known to cause autocrine function, which further exacerbates the situation. In NSCLC, KRAS mutations have a strong positive correlation with the disease, particularly in patients with a smoking history. In pancreatic cancer, KRAS mutations are a dominant pathological basis, with most mutations being G12D, G12V, G13D, G13C, G13S, and G13R. These mutations serve as initial markers in tumorigenesis and are associated with poor prognosis and high mortality rates. In colorectal cancer, KRAS mutations contribute to 4/5 of cases, with cellular mechanisms involving the MAPK pathway, which resists anti-epidermal growth factor antibodies. In Low-grade Serous Ovarian Cancer (LGSOC), KRAS mutations are associated with altered signaling in the MAPK pathway and drug resistance. However, treatments such as Selumetinib, a down regulator of RAS/Rapidly Accelerated Fibrosarcoma (RAF)/Mitogen-activated protein kinase (MEK) pathways, and a combination of trametinib and buparlisib have shown promise in managing LGSOC when diagnosed early through KRAS mutation markers. Although KRAS mutations are commonly associated with many types of cancer, their use in clinical practice is limited due to the lack of accurate methods to identify them. It is needed to further isolate the KRAS mutation products and correlate the cancer-causing genes to make it a promising approach for cancer chemotherapy.