The sex-based differences between the effects of two novel sugar-based drug candidates,a sulfated polymannuroguluronate(SPMG-911)and an acidic oligosaccharide sugar chain compound(AOSC-971),on the enzymes CYP 1A2,CYP2...The sex-based differences between the effects of two novel sugar-based drug candidates,a sulfated polymannuroguluronate(SPMG-911)and an acidic oligosaccharide sugar chain compound(AOSC-971),on the enzymes CYP 1A2,CYP2E1 and CYP3A4 of Chinese human liver microsome were investigated.The results showed that neither SPMG-911 nor AOSC-971 have any effect on CYP3A4,AOSC-971 induced the CYP 2E1 in men but have no effect on CYP1A2,SPMG-911 inhibit the CYP1A2 also in men but have no effect on CYP2E1.The results are useful for their safety evaluation,as well as for the prediction of inter-drug interactions associated with the two drugs.展开更多
Esophageal squamous cell carcinoma(ESCC),the major subtype of esophageal carcinoma(ESCA),is one of the most lethal malignancies worldwide.This study aimed to identify potential biomarkers and/or therapeutic targets fo...Esophageal squamous cell carcinoma(ESCC),the major subtype of esophageal carcinoma(ESCA),is one of the most lethal malignancies worldwide.This study aimed to identify potential biomarkers and/or therapeutic targets for ESCC.The datasets GSE44021,GSE77861,GSE20347,and GSE29001 retrieved from the Gene Expression Omnibus(GEO)database contained 117 ESCC tissues and 109 normal tissues.Differentially expressed genes(DEGs)associated with ESCC were identified using the GEO2R tool.Dysregulated pathways associated with ESCC mainly included mitotic regulation,cell cycle,ECM-receptor interaction,DNA replication,etc.The protein-protein interaction(PPI)network of overlapping DEGs was constructed and nine key genes(KGs)were identified from the complex interaction network using Degree,maximum neighborhood component(MNC),and maximal clique centrality(MCC)algorithms.Expression patterns of KGs at the transcriptional and translational levels were validated using ESCC-related data from the Cancer Genome Atlas(TCGA),Oncomine,and Human Protein Atlas(HPA)databases.Genetic alterations calculation,immune cell infiltrates evaluation,methylation analysis,prognostic analysis,transcription factors(TFs)and miRNAs regulatory networks construction,and targeted drug prediction were further performed.It was also found that the knockout of these KGs affected the survival of more than two types of ESCC cells by genome-wide CRISPR-Cas9 dropout screens.In conclusion,we identified KGs,TFs,and miRNAs with biomarker potential(e.g.,NDC80,BUB1,TOP2A,AURKA,AURKB,TTK,UBE2C,TPX2,BUB1B,E2F1,and hsa-miR-483-5p)and 23 candidate targeted drugs for ESCC by utilizing an integrated multi-omics approach.These findings provide additional insights into uncovering the molecular mechanism and improving the efficiency of clinical diagnosis and treatment for ESCC.展开更多
Mostly candida resides as an opportunistic organism on epithelial surfaces of human being. However, under auspicious conditions can cause infections including serious life threatening invasive candidiasis with subsequ...Mostly candida resides as an opportunistic organism on epithelial surfaces of human being. However, under auspicious conditions can cause infections including serious life threatening invasive candidiasis with subsequent mortality particularly in immune deficit and hospitalized patients having co-morbids. Limited data are published on the prevalence of candidiasis, based on the researches conducted at few tertiary care settings which are not representing the overall disease burden in our country, Pakistan. Therefore, this study was conducted to evaluate the frequency and sensitivity patterns of candidiasis in our community. Methods: Out of total 1020 specimens, 130 clinical samples were identified as candidal positive, obtained from March to May 2018. These samples were isolated from vagina, oropharynx, urine, tracheal aspirates, pus, blood, tips of the intubations, wounds and fluids of the body cavities. Identification of candida, its species and antifungal sensitivity screening was done by Kirby Bauer’s disk diffusion method according to CLSI guide lines’ (M - 44 A2 series, 2009). Results: A significant majority, 80 (61.5%) of candidal strains were isolated from females with female to male ratio 8:5 and most of these isolates were obtained from high vaginal swabs (43.75%). Four candidal species (Candida albicans 80%, Candida tropicalis 10%, Candida glabrata 9.2% and Candida ciferrii 0.8%) were isolated from all positive specimens. Maximum number of the positive samples 52 (40%) were obtained from ICU patients. Sensitivity test of candidal positive samples revealed that commonly used azole antifungal drugs, fluconazole and voriconazole were highly resistant, with respective 57.7% and 70.8% resistance. Conclusion: Candidiasis is highly prevalent in our clinical set up and more frequently infecting females in comparison to males as most of the positive isolates were retrieved from HVS (high vaginal swabs). Still, C. albicans was found to be the most prevalent specie isolated among all candida samples. Our study also demonstrated that the resistance of most commonly prescribed antifungals, azoles have shown a rapid rise. Therefore, it is recommended that before prescription of antifungal drugs the clinicians should routinely recommend culture and sensitivity testing of samples taken from candida infected individuals.展开更多
Immuno-oncology represents a groundbreaking and well-established field within cancer treatment.Among the various immuno-oncology targets,the exploration of programmed cell death-1/ligand-1 for drug discovery has prove...Immuno-oncology represents a groundbreaking and well-established field within cancer treatment.Among the various immuno-oncology targets,the exploration of programmed cell death-1/ligand-1 for drug discovery has proven to be one of the most successful endeavors.Remarkably,it took nearly 30 years from the initial target identification to the clinical approval of monoclonal antibodies.Providing suitable and reliable bioassays for drug candidate evaluation is of paramount importance throughout the early stages of drug discovery,from lead compound identification to in vivo efficacy testing.This assay review aims to shed light on diverse assays reported in the literature for testing antagonism activity and efficacy of programmed cell death-1/ligand-1 inhibitors.Each of these assays possesses inherent advantages and can be applied in different research scenarios.The insights presented in this summary can serve as a valuable resource for scientists in this field,aiding in the selection of appropriate assays for their specific investigations.展开更多
文摘The sex-based differences between the effects of two novel sugar-based drug candidates,a sulfated polymannuroguluronate(SPMG-911)and an acidic oligosaccharide sugar chain compound(AOSC-971),on the enzymes CYP 1A2,CYP2E1 and CYP3A4 of Chinese human liver microsome were investigated.The results showed that neither SPMG-911 nor AOSC-971 have any effect on CYP3A4,AOSC-971 induced the CYP 2E1 in men but have no effect on CYP1A2,SPMG-911 inhibit the CYP1A2 also in men but have no effect on CYP2E1.The results are useful for their safety evaluation,as well as for the prediction of inter-drug interactions associated with the two drugs.
基金supported by the Innovation Capacity Building Project of the Jilin Provincial Development and Reform Commission(2021C041-1).
文摘Esophageal squamous cell carcinoma(ESCC),the major subtype of esophageal carcinoma(ESCA),is one of the most lethal malignancies worldwide.This study aimed to identify potential biomarkers and/or therapeutic targets for ESCC.The datasets GSE44021,GSE77861,GSE20347,and GSE29001 retrieved from the Gene Expression Omnibus(GEO)database contained 117 ESCC tissues and 109 normal tissues.Differentially expressed genes(DEGs)associated with ESCC were identified using the GEO2R tool.Dysregulated pathways associated with ESCC mainly included mitotic regulation,cell cycle,ECM-receptor interaction,DNA replication,etc.The protein-protein interaction(PPI)network of overlapping DEGs was constructed and nine key genes(KGs)were identified from the complex interaction network using Degree,maximum neighborhood component(MNC),and maximal clique centrality(MCC)algorithms.Expression patterns of KGs at the transcriptional and translational levels were validated using ESCC-related data from the Cancer Genome Atlas(TCGA),Oncomine,and Human Protein Atlas(HPA)databases.Genetic alterations calculation,immune cell infiltrates evaluation,methylation analysis,prognostic analysis,transcription factors(TFs)and miRNAs regulatory networks construction,and targeted drug prediction were further performed.It was also found that the knockout of these KGs affected the survival of more than two types of ESCC cells by genome-wide CRISPR-Cas9 dropout screens.In conclusion,we identified KGs,TFs,and miRNAs with biomarker potential(e.g.,NDC80,BUB1,TOP2A,AURKA,AURKB,TTK,UBE2C,TPX2,BUB1B,E2F1,and hsa-miR-483-5p)and 23 candidate targeted drugs for ESCC by utilizing an integrated multi-omics approach.These findings provide additional insights into uncovering the molecular mechanism and improving the efficiency of clinical diagnosis and treatment for ESCC.
文摘Mostly candida resides as an opportunistic organism on epithelial surfaces of human being. However, under auspicious conditions can cause infections including serious life threatening invasive candidiasis with subsequent mortality particularly in immune deficit and hospitalized patients having co-morbids. Limited data are published on the prevalence of candidiasis, based on the researches conducted at few tertiary care settings which are not representing the overall disease burden in our country, Pakistan. Therefore, this study was conducted to evaluate the frequency and sensitivity patterns of candidiasis in our community. Methods: Out of total 1020 specimens, 130 clinical samples were identified as candidal positive, obtained from March to May 2018. These samples were isolated from vagina, oropharynx, urine, tracheal aspirates, pus, blood, tips of the intubations, wounds and fluids of the body cavities. Identification of candida, its species and antifungal sensitivity screening was done by Kirby Bauer’s disk diffusion method according to CLSI guide lines’ (M - 44 A2 series, 2009). Results: A significant majority, 80 (61.5%) of candidal strains were isolated from females with female to male ratio 8:5 and most of these isolates were obtained from high vaginal swabs (43.75%). Four candidal species (Candida albicans 80%, Candida tropicalis 10%, Candida glabrata 9.2% and Candida ciferrii 0.8%) were isolated from all positive specimens. Maximum number of the positive samples 52 (40%) were obtained from ICU patients. Sensitivity test of candidal positive samples revealed that commonly used azole antifungal drugs, fluconazole and voriconazole were highly resistant, with respective 57.7% and 70.8% resistance. Conclusion: Candidiasis is highly prevalent in our clinical set up and more frequently infecting females in comparison to males as most of the positive isolates were retrieved from HVS (high vaginal swabs). Still, C. albicans was found to be the most prevalent specie isolated among all candida samples. Our study also demonstrated that the resistance of most commonly prescribed antifungals, azoles have shown a rapid rise. Therefore, it is recommended that before prescription of antifungal drugs the clinicians should routinely recommend culture and sensitivity testing of samples taken from candida infected individuals.
文摘Immuno-oncology represents a groundbreaking and well-established field within cancer treatment.Among the various immuno-oncology targets,the exploration of programmed cell death-1/ligand-1 for drug discovery has proven to be one of the most successful endeavors.Remarkably,it took nearly 30 years from the initial target identification to the clinical approval of monoclonal antibodies.Providing suitable and reliable bioassays for drug candidate evaluation is of paramount importance throughout the early stages of drug discovery,from lead compound identification to in vivo efficacy testing.This assay review aims to shed light on diverse assays reported in the literature for testing antagonism activity and efficacy of programmed cell death-1/ligand-1 inhibitors.Each of these assays possesses inherent advantages and can be applied in different research scenarios.The insights presented in this summary can serve as a valuable resource for scientists in this field,aiding in the selection of appropriate assays for their specific investigations.
