N6-methyladenosine(m^(6)A), the most prevalent and conserved RNA modification in eukaryotic cells, profoundly influences virtually all aspects of mRNA metabolism. mRNA plays crucial roles in neural stem cell genesis a...N6-methyladenosine(m^(6)A), the most prevalent and conserved RNA modification in eukaryotic cells, profoundly influences virtually all aspects of mRNA metabolism. mRNA plays crucial roles in neural stem cell genesis and neural regeneration, where it is highly concentrated and actively involved in these processes. Changes in m^(6)A modification levels and the expression levels of related enzymatic proteins can lead to neurological dysfunction and contribute to the development of neurological diseases. Furthermore, the proliferation and differentiation of neural stem cells, as well as nerve regeneration, are intimately linked to memory function and neurodegenerative diseases. This paper presents a comprehensive review of the roles of m^(6)A in neural stem cell proliferation, differentiation, and self-renewal, as well as its implications in memory and neurodegenerative diseases. m^(6)A has demonstrated divergent effects on the proliferation and differentiation of neural stem cells. These observed contradictions may arise from the time-specific nature of m^(6)A and its differential impact on neural stem cells across various stages of development. Similarly, the diverse effects of m^(6)A on distinct types of memory could be attributed to the involvement of specific brain regions in memory formation and recall. Inconsistencies in m^(6)A levels across different models of neurodegenerative disease, particularly Alzheimer's disease and Parkinson's disease, suggest that these disparities are linked to variations in the affected brain regions. Notably, the opposing changes in m^(6)A levels observed in Parkinson's disease models exposed to manganese compared to normal Parkinson's disease models further underscore the complexity of m^(6)A's role in neurodegenerative processes. The roles of m^(6)A in neural stem cell proliferation, differentiation, and self-renewal, and its implications in memory and neurodegenerative diseases, appear contradictory. These inconsistencies may be attributed to the timespecific nature of m^(6)A and its varying effects on distinct brain regions and in different environments.展开更多
Objective INF2 is a member of the formins family.Abnormal expression and regulation of INF2 have been associated with the progression of various tumors,but the expression and role of INF2 in hepatocellular carcinoma(H...Objective INF2 is a member of the formins family.Abnormal expression and regulation of INF2 have been associated with the progression of various tumors,but the expression and role of INF2 in hepatocellular carcinoma(HCC)remain unclear.HCC is a highly lethal malignant tumor.Given the limitations of traditional treatments,this study explored the expression level,clinical value and potential mechanism of INF2 in HCC in order to seek new therapeutic targets.Methods In this study,we used public databases to analyze the expression of INF2 in pan-cancer and HCC,as well as the impact of INF2 expression levels on HCC prognosis.Quantitative real time polymerase chain reaction(RT-qPCR),Western blot,and immunohistochemistry were used to detect the expression level of INF2 in liver cancer cells and human HCC tissues.The correlation between INF2 expression and clinical pathological features was analyzed using public databases and clinical data of human HCC samples.Subsequently,the effects of INF2 expression on the biological function and Drp1 phosphorylation of liver cancer cells were elucidated through in vitro and in vivo experiments.Finally,the predictive value and potential mechanism of INF2 in HCC were further analyzed through database and immunohistochemical experiments.Results INF2 is aberrantly high expression in HCC samples and the high expression of INF2 is correlated with overall survival,liver cirrhosis and pathological differentiation of HCC patients.The expression level of INF2 has certain diagnostic value in predicting the prognosis and pathological differentiation of HCC.In vivo and in vitro HCC models,upregulated expression of INF2 triggers the proliferation and migration of the HCC cell,while knockdown of INF2 could counteract this effect.INF2 in liver cancer cells may affect mitochondrial division by inducing Drp1 phosphorylation and mediate immune escape by up-regulating PD-L1 expression,thus promoting tumor progression.Conclusion INF2 is highly expressed in HCC and is associated with poor prognosis.High expression of INF2 may promote HCC progression by inducing Drp1 phosphorylation and up-regulation of PD-L1 expression,and targeting INF2 may be beneficial for HCC patients with high expression of INF2.展开更多
Objectives:Epibrassinolide(EBR)is a steroid hormone with anti-tumor properties.Nevertheless,its potential to inhibit gastric cancer(GC)cells remains unknown.The aim of this research was to examine the effects of EBR o...Objectives:Epibrassinolide(EBR)is a steroid hormone with anti-tumor properties.Nevertheless,its potential to inhibit gastric cancer(GC)cells remains unknown.The aim of this research was to examine the effects of EBR on GC cells and to investigate the specific mechanism of EBR.Methods:A cell counting kit-8(CCK-8)assay was utilized to determine cell survival rates.The investigation of apoptosis,cell cycle progression,and reactive oxygen species(ROS)levels was performed using flow cytometry.To detect cell migration,a wound-healing assay was performed on AGS cells.Furthermore,western blotting assay was utilized to determine protein expression levels.Results:The CCK-8 assay demonstrated that EBR reduced the survival rates of AGS,KATO-3,and MKN-45 cells,while causing only minor toxicity to normal cells.The apoptosis assay indicated that EBR induced AGS cell apoptosis through a mitochondria-mediated pathway.Western blotting results demonstrated that EBR induced AGS cell apoptosis via mitogen-activated protein kinase(MAPK)/signal transducer and activator of transcription 3(STAT3)/nuclear factor kappa B(NF-κB)signaling pathway.Further,after treating AGS cells with EBR,the accumulation of intracellular ROS markedly increased.EBR also induced G2/M phase cell cycle arrest in AGS cells by downregulating phospho-protein kinase B(p-AKT),cyclin-dependent kinase 1/2(CDK1/2),and cyclin B1 expression levels,while simultaneously upregulating p21 and p27 expression levels.EBR inhibited AGS cell migration by downregulating p-AKT,phosphorylated-glycogen synthase kinase 3β(p-GSK-3β),andβ-catenin expression levels and upregulating E-cadherin expression levels.However,these effects were reversed by pretreatment with N-acetylcysteine(NAC).Conclusion:EBR regulates AGS cells by inducing apoptosis and G2/M phase arrest,while also inhibiting cell migration,all of which are mediated through ROS-mediated signaling pathways.Ultimately,these effects suggest a significant role for EBR in regulating cellular processes within AGS cells.展开更多
Dear Editor,Pyruvate dehydrogenase complex(PDHc) is a large multienzyme assembly(Mr = 4–10 million Daltons) consisting of three essential components: pyruvate dehydrogenase(E1p), dihydrolipoyl transacetylase(E2p), an...Dear Editor,Pyruvate dehydrogenase complex(PDHc) is a large multienzyme assembly(Mr = 4–10 million Daltons) consisting of three essential components: pyruvate dehydrogenase(E1p), dihydrolipoyl transacetylase(E2p), and dihydrolipoyl dehydrogenase(E3). These three enzymes perform distinct functions sequentially to catalyze the oxidative decarboxylation of pyruvate with formation of nicotinamide adenine dinucleotide(NADH) and acetyl-coenzyme A(Patel and Roche, 1990).展开更多
Country bean, Lablab purpureus (L.) is considered one of the most important leguminous crops, but their cultivation under drought stress condition encounters challenges. In this study, an experiment has been conducted...Country bean, Lablab purpureus (L.) is considered one of the most important leguminous crops, but their cultivation under drought stress condition encounters challenges. In this study, an experiment has been conducted among 30 genotypes under drought condition to explore morphological diversity of qualitative and quantitative, biochemical, molecular analysis. The study identified significant variations in eight traits among the genotypes examined, with phenotypic variance exceeding genotypic variance, indicating both genetic and environmental influences. High heritability and genetic advance were observed in primary, secondary, and tertiary branch lengths, suggesting these traits are likely controlled by additive gene effects, making them effective targets for selection. Principal component analysis identified three components that made a substantial contribution, accounting for approximately 73.06% of the overall quantitative variations. Among the quantitative traits, the highest coefficient of variation (CV%) has been found in number of flowers (55.05%). While number of primary branches, primary branch length, number of secondary branches, secondary branch length, number of tertiary branches, tertiary branch length has individually more than 20% of CV%. The genotypes have been grouped into three clusters based on quantitative traits. Analysis of protein reveals that the genotypes of DS28 and DS29 have higher protein content than other genotypes. Dehydrogenase responsive genotypes have been found on DS28 and DS29 from the molecular analysis. The results suggest that the genotypes DS28 and DS29 could contribute as genetic resource of high protein content and DREB responsive, and the eight quantitative traits of 30 genotypes could be used for further breeding programme.展开更多
Water-saving irrigation strategies can successfully alleviate methane emissions from rice fields,but significantly stimulate nitrous oxide(N_(2)O)emissions because of variations in soil oxygen level and redox potentia...Water-saving irrigation strategies can successfully alleviate methane emissions from rice fields,but significantly stimulate nitrous oxide(N_(2)O)emissions because of variations in soil oxygen level and redox potential.However,the relationship linking soil N_(2)O emissions to nitrogen functional genes during various fertilization treatments in water-saving paddy fields has rarely been investigated.Furthermore,the mitigation potential of organic fertilizer substitution on N_(2)O emissions and the microbial mechanism in rice fields must be further elucidated.Our study examined how soil N_(2)O emissions were affected by related functional microorganisms(ammonia-oxidizing archaea(AOA),ammonia-oxidizing bacteria(AOB),nirS,nirK and nosZ)to various fertilization treatments in a rice field in southeast China over two years.In this study,three fertilization regimes were applied to rice cultivation:a no nitrogen(N)(Control),an inorganic N(Ni),and an inorganic N with partial N substitution with organic manure(N_(i)+N_(o)).Over two rice-growing seasons,cumulative N_(2)O emissions averaged 0.47,4.62 and 4.08 kg ha^(−1)for the Control,Ni and N_(i)+N_(o)treatments,respectively.In comparison to the Ni treatment,the N_(i)+N_(o)fertilization regime considerably reduced soil N_(2)O emissions by 11.6%while maintaining rice yield,with a lower N_(2)O emission factor(EF)from fertilizer N of 0.95%.Nitrogen fertilization considerably raised the AOB,nirS,nirK and nosZ gene abundances,in comparison to the Control treatment.Moreover,the substitution of organic manure for inorganic N fertilizer significantly decreased AOB and nirS gene abundances and increased nosZ gene abundance.The AOB responded to N fertilization more sensitively than the AOA.Total N_(2)O emissions significantly correlated positively with AOB and nirS gene abundances while having a negative correlation with nosZ gene abundance and the nosZ/nirS ratio across N-fertilized plots.In summary,we conclude that organic manure substitution for inorganic N fertilizer decreased soil N_(2)O emissions primarily by changing the soil NO_(3)^(−)-N,pH and DOC levels,thus inhibiting the activities of ammonia oxidation in nitrification and nitrite reduction in denitrification,and strengthening N_(2)O reduction in denitrification from water-saving rice paddies.展开更多
Islet beta cells(β-cells)produce insulin in response to high blood glucose levels,which is essential for preserving glucose homeostasis.Voltage-gated ion channels inβ-cells,including Na+,K+,and Ca2+channels,aid in t...Islet beta cells(β-cells)produce insulin in response to high blood glucose levels,which is essential for preserving glucose homeostasis.Voltage-gated ion channels inβ-cells,including Na+,K+,and Ca2+channels,aid in the release of insulin.The epithelial sodium channel alpha subunit(α-ENaC),a voltage-independent sodium ion channel,is also expressed in human pancreatic endocrine cells.However,there is no reported study on the function of ENaC in theβ-cells.In the current study,we found thatα-ENaC was expressed in human pancreatic glandule and pancreatic isletβ-cells.In the pancreas of db/db mice and high-fat diet-induced mice,and in mouse isletβ-cells(MIN6 cells)treated with palmitate,α-ENaC expression was increased.Whenα-ENaC was overexpressed in MIN6 cells,insulin content and glucose-induced insulin secretion were significantly reduced.On the other hand,palmitate injured isletβ-cells and suppressed insulin synthesis and secretion,but increasedα-ENaC expression in MIN6 cells.However,α-ENaC knockout(Scnn1a−/−)in MIN6 cells attenuatedβ-cell disorder induced by palmitate.Furthermore,α-ENaC regulated the ubiquitylation and degradation of sirtuin 2 inβ-cells.α-ENaC also modulatedβ-cell function in correlation with the inositol-requiring enzyme 1 alpha/X-box binding protein 1(IRE1α/XBP1)and protein kinase RNA-like endoplasmic reticulum kinase/C/EBP homologous protein(PERK/CHOP)endoplasmic reticulum stress pathways.These results suggest thatα-ENaC may play a novel role in insulin synthesis and secretion in theβ-cells,and the upregulation ofα-ENaC promotes isletβ-cell dysfunction.In conclusion,α-ENaC may be a key regulator involved in isletβ-cell damage and a potential therapeutic target for type 2 diabetes mellitus.展开更多
Osteoporosis,a metabolic bone disease characterized by low bone mineral density and deterioration of bone microarchitecture,has led to a high risk of fatal osteoporotic fractures worldwide.Accumulating evidence has re...Osteoporosis,a metabolic bone disease characterized by low bone mineral density and deterioration of bone microarchitecture,has led to a high risk of fatal osteoporotic fractures worldwide.Accumulating evidence has revealed that sexual dimorphism is a notable feature of osteoporosis,with sex-specific differences in epidemiology and pathogenesis.Specifically,females are more susceptible than males to osteoporosis,while males are more prone to disability or death from the disease.To date,sex chromosome abnormalities and steroid hormones have been proven to contribute greatly to sexual dimorphism in osteoporosis by regulating the functions of bone cells.Understanding the sex-specific differences in osteoporosis and its related complications is essential for improving treatment strategies tailored to women and men.This literature review focuses on the mechanisms underlying sexual dimorphism in osteoporosis,mainly in a population of aging patients,chronic glucocorticoid administration,and diabetes.Moreover,we highlight the implications of sexual dimorphism for developing therapeutics and preventive strategies and screening approaches tailored to women and men.Additionally,the challenges in translating bench research to bedside treatments and future directions to overcome these obstacles will be discussed.展开更多
Coronavirus disease 2019(COVID-19)is a kind of viral pneumonia which is caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).The emergence of SARS-CoV-2 has been marked as the third introduction of a ...Coronavirus disease 2019(COVID-19)is a kind of viral pneumonia which is caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).The emergence of SARS-CoV-2 has been marked as the third introduction of a highly pathogenic coronavirus into the human population after the severe acute respiratory syndrome coronavirus(SARS-CoV)and the Middle East respiratory syndrome coro-navirus(MERS-CoV)in the twenty-first century.In this minireview,we provide a brief introduction of the general features of SARS-CoV-2 and discuss current knowledge of molecular immune pathogenesis,diagnosis and treatment of COVID-19 on the base of the present understanding of SARS-CoV and MERS-CoV infections,which may be helpful in offering novel insights and potential therapeutic targets for combating the SARS-CoV-2 infection.展开更多
As a key contributor to memory storage, the synapse is one of the earliest affected neuronal components in Alzheimer＇s disease （AD）. Under physiological conditions, the synaptic con- nections between neurons underg...As a key contributor to memory storage, the synapse is one of the earliest affected neuronal components in Alzheimer＇s disease （AD）. Under physiological conditions, the synaptic con- nections between neurons undergo activity-dependent func- tional and morphological re-organisation. This dynamic, ＇plastic＇ neural ability critically depends on the structural integrity of the synapse. Thus, proteins that are implicated in preserving the organisation and dynamics of synaptic connections, including microtubules of the cytoskeleton and associated proteins, have attracted much focus for their involvement in the malfunction- ing AD synapse.展开更多
Objectives:Deletion of Fscn2 gene in mice has been linked to progressive hearing loss and degeneration of cochlear cells.Cisplatin,an antitumor drug,can cause various side effects,including ototoxicity.The aim of this...Objectives:Deletion of Fscn2 gene in mice has been linked to progressive hearing loss and degeneration of cochlear cells.Cisplatin,an antitumor drug,can cause various side effects,including ototoxicity.The aim of this study was to investigate the effects of Fscn2 on cisplatin-induced hearing impairment in mice and to explore the possible mechanism.Methods:Two-week-old Fscn2^(+/+)mice and Fscn2^(−/−)mice were treated with two doses of cisplatin,with a 3-day recovery period in between.ABR(auditory evoked brain stem response)thresholds were measured and cochlear pathology was observed at 3 weeks of age.Results:Both Fscn2^(+/+)and Fscn2^(−/−)mice showed hearing loss under the effect of cisplatin,but the impairment was more severe in Fscn2^(−/−)mice.Further experiments showed that the percentages of outer hair cell(OHC)and spiral ganglion neuron(SGN)loss were significantly higher in cisplatin-treated Fscn2^(−/−)mice compared to Fscn2^(+/+)mice.Additionally,knockdown of Fscn2 in HEI-OC1 cells worsened cisplatin-induced cell apoptosis.Conclusion:FSCN2 mediates reduction of CDDP induced ototoxicity by inhibiting cell apoptosis.展开更多
Wnt signaling are critical pathway involved in organ development, tumorigenesis, and cancer progression. WNT7A, a member of the Wnt family, remains poorly understood in terms of its role and the underlying molecular m...Wnt signaling are critical pathway involved in organ development, tumorigenesis, and cancer progression. WNT7A, a member of the Wnt family, remains poorly understood in terms of its role and the underlying molecular mechanisms it entails in head and neck squamous cell carcinoma (HNSCC). According to the Cancer Genome Atlas (TCGA), transcriptome sequencing data of HNSCC, the expression level of WNT7A in tumors was found to be higher than in adjacent normal tissues, which was validated using Real-time RT-PCR and immunohistochemistry. Unexpectedly, overexpression of WNT7A did not activate the canonical Wnt-β-catenin pathway in HNSCC. Instead, our findings suggested that WNT7A potentially activated the FZD7/JAK1/STAT3 signaling pathway, leading to enhanced cell proliferation, self-renewal, and resistance to apoptosis. Furthermore, in a patient-derived xenograft (PDX) tumor model, high expression of WNT7A and phosphorylated STAT3 was observed, which positively correlated with tumor progression.These findings underscore the significance of WNT7A in HNSCC progression and propose the targeting of key molecules within the FZD7/JAK1/STAT3 pathway as a promising strategy for precise treatment of HNSCC.展开更多
Objective:To elucidate the biological basis of the heart qi deficiency(HQD)pattern,an in-depth understanding of which is essential for improving clinical herbal therapy.Methods: We predicted and characterized HQD patt...Objective:To elucidate the biological basis of the heart qi deficiency(HQD)pattern,an in-depth understanding of which is essential for improving clinical herbal therapy.Methods: We predicted and characterized HQD pattern genes using the new strategy,TCM-HIN2Vec,which involves heterogeneous network embedding and transcriptomic experiments.First,a heterogeneous network of traditional Chinese medicine(TCM)patterns was constructed using public databases.Next,we predicted HQD pattern genes using a heterogeneous network-embedding algorithm.We then analyzed the functional characteristics of HQD pattern genes using gene enrichment analysis and examined gene expression levels using RNA-seq.Finally,we identified TCM herbs that demonstrated enriched interactions with HQD pattern genes via herbal enrichment analysis.Results: Our TCM-HIN2Vec strategy revealed that candidate genes associated with HQD pattern were significantly enriched in energy metabolism,signal transduction pathways,and immune processes.Moreover,we found that these candidate genes were significantly differentially expressed in the transcriptional profile of mice model with heart failure with a qi deficiency pattern.Furthermore,herbal enrichment analysis identified TCM herbs that demonstrated enriched interactions with the top 10 candidate genes and could potentially serve as drug candidates for treating HQD.Conclusion: Our results suggested that TCM-HIN2Vec is capable of not only accurately identifying HQD pattern genes,but also deciphering the basis of HQD pattern.Furthermore our finding indicated that TCM-HIN2Vec may be further expanded to develop other patterns,leading to a new approach aimed at elucidating general TCM patterns and developing precision medicine.展开更多
In this letter,we comment on a recent publication by Mei et al,in the World Journal of Hepatology,investigating the hepatoprotective effects of the modified Xiaoyao San(MXS)formula in a male rat model of non-alcoholic...In this letter,we comment on a recent publication by Mei et al,in the World Journal of Hepatology,investigating the hepatoprotective effects of the modified Xiaoyao San(MXS)formula in a male rat model of non-alcoholic steatohepatitis(NASH).The authors found that MXS treatment mitigated hepatic steatosis and inflam-mation in the NASH model,as evidenced by the reduction in lipid droplets(LDs),fibrosis markers and lipogenic factors.Interestingly,these hepatoprotective effects were associated with androgen upregulation(based on metabolomics analysis of male steroid hormone metabolites),adenosine 5’-monophosphate-activated protein kinase(AMPK)activation,and restoration of phosphatase and tensin homolog(PTEN)expression.However,the authors did not clearly discuss the relationships between MXS-induced hepatic steatosis reduction in the NASH model,and androgen upregulation,AMPK activation,and restoration of PTEN expression.This editorial emphasizes the reported mechanisms and explains how they act or interact with each other to reduce hepatic steatosis and inflammation in the NASH model.As a perspective,we propose additional mechanisms(such as autophagy/lipophagy activation in hepatocytes)for the clearance of LDs and suppression of hepatic steatosis by MXS in the NASH model.A proper understanding of the mechanisms of MXS-induced reduction of hepatic steatosis might help in the treatment of NASH and related diseases.展开更多
Coronavirus disease 2019(COVID-19)has been a pandemic for more than a year.With the expanding second wave of the pandemic in winter,the continuous evolution of SARS-CoV-2 has brought new issues,including the significa...Coronavirus disease 2019(COVID-19)has been a pandemic for more than a year.With the expanding second wave of the pandemic in winter,the continuous evolution of SARS-CoV-2 has brought new issues,including the significance of virus mutations in infection and the detection of asymptomatic infection.In this review,we first introduced several major SARS-CoV-2 mutations since the COVID-19 outbreak and then mentioned the widely used molecular detection techniques to diagnose COVID-19,primarily focusing on their strengths and limitations.We further discussed the effects of viral genetic variation and asymptomatic infection on the molecular detection of SARS-CoV-2 infection.The review finally summarized useful insights into the molecular diagnosis of COVID-19 under the special situation being challenged by virus mutation and asymptomatic infection.展开更多
Allergic inflammation is closely related to the activation of mast cells(MCs),which is regulated by its intracellular Ca^(2+) plevel,but the intake and effects of the intracellular Ca^(2+) premain unclear.The Ca^(2+) ...Allergic inflammation is closely related to the activation of mast cells(MCs),which is regulated by its intracellular Ca^(2+) plevel,but the intake and effects of the intracellular Ca^(2+) premain unclear.The Ca^(2+) pinflux is controlled by members of Ca^(2+) pchannels,among which calcium voltage-gated channel subunit alpha1 C(CaV1.2)is the most robust.This study aimed to reveal the role and underlying mechanism of MC CaV1.2 in allergic inflammation.We found that CaV1.2 participated in MC activation and allergic inflammation.Nimodipine(Nim),as a strong CaV1.2-specific antagonist,ameliorated allergic inflammation in mice.Further,CaV1.2 activation in MC was triggered by phosphatizing at its Ser1928 through protein kinase C(PKC),which calcium/calmodulin-dependent protein kinase II(CaMKII)catalyzed.Overexpression or knockdown of MC CaV1.2 influenced MC activation.Importantly,CaV1.2 expression in MC had detrimental effects,while its deficiency ameliorated allergic pulmonary inflammation.Results provide novel insights into CaV1.2 function and a potential drug target for controlling allergic inflammation.展开更多
Background: Hepatocellular carcinoma (HCC) is the most common type of liver cancer and one of the leading causes of cancer-related death worldwide. Advanced HCC displays strong resistance to chemotherapy, and traditio...Background: Hepatocellular carcinoma (HCC) is the most common type of liver cancer and one of the leading causes of cancer-related death worldwide. Advanced HCC displays strong resistance to chemotherapy, and traditional chemotherapy drugs do not achieve satisfactory therapeutic efficacy. The delivery of therapeutic compounds to the target site is a major challenge in the treatment of many diseases. Objective: This study aims to evaluate activated charcoal nanoparticles as a drug delivery system for anticancer agents (Sorafenib and Doxorubicin) in Hepatocellular Cancer Stem Cells. Method: The percent efficiency of entrapment (% EE) of the doxorubicin and sorafenib entrapped onto the activated charcoal was obtained by determining the free doxorubicin and sorafenib concentration in the supernatant-prepared solutions. Then the characterizations of nanoparticles were formed by determination of the particle size distribution, zeta potential, and polydispersity index (PDI). The anticancer activity of activated Charcoal, Doxorubicin-ACNP, sorafenib-ACNP, free doxorubicin, and free sorafenib solutions was measured based on cell viability percentage in HepG2 cell lines (ATCC-CCL 75). In vitro RBC’s toxicity of Doxorubicin/sorafenib loaded charcoal was estimated by hemolysis percentage. Results: The synthesized Doxorubicin-ACNP and Sorafenib-ACNP were evaluated and their physiochemical properties were also examined. Essentially, the percent Efficiency of Entrapment (EE %) was found to be 87.5% and 82.66% for Doxorubicin-ACNP and Sorafenib-ACNP, respectively. The loading capacity was 34.78% and 24.31% for Doxorubicin-ACNP and Sorafenib-ACNP. Using the Dynamic Light scattering [DLS] for the determination of the hydrodynamic size and surface zeta potential, a narrow sample size distribution was obtained of (18, 68, and 190 nm for charcoal, 105, 255, and 712 nm for doxorubicin, and 91, 295, and 955 nm for sorafenib), respectively. A surface charge of −13.2, −15.6 and −17 was obtained for charcoal, doxorubicin/charcoal, and sorafenib/charcoal nanoparticles. The cytotoxic activity of Doxorubicin-ACNP and Sorafenib-ACNP was evaluated in-vitro against HepG2 cell lines and it was observed that Drug loaded ACNP improved anticancer activity when compared to Doxorubicin or Sorafenib alone. Moreover, testing the toxicity potential of DOX-ACNP and Sorafenib-ACNP showed a significant reduction in the hemolysis of red blood cells when compared to Doxorubicin and Sorafenib alone. Conclusion: In conclusion, it is notable to state that this study is regarded as the first to investigate the use of Activated charcoal for the loading of Doxorubicin and Sorafenib for further use in the arena of hepatocellular carcinoma. Doxorubicin-ACNP and Sorafenib-ACNP showed noteworthy anticancer activity along with a reduced potential of RBCs hemolysis rendering it as an efficacious carrier with a low toxicity potential.展开更多
Objectives To analyze the clinical profile,adequacy of treatment with rivaroxaban and outcomes in octogenarians with atrial fibrillation(AF),taking rivaroxaban in clinical practice.Methods Observational and non-interv...Objectives To analyze the clinical profile,adequacy of treatment with rivaroxaban and outcomes in octogenarians with atrial fibrillation(AF),taking rivaroxaban in clinical practice.Methods Observational and non-interventional study that included AF adults recruited from 79 Spanish centers,anticoagulated with rivaroxaban ≥ 6 months before being included.Data were analyzed according to age(≥ 80 vs.< 80 years) at baseline.Results Out of 1433 patients,453(31.6%) were octogenarians at baseline.Compared to younger patients,octogenarians had more comorbidities,higher CHA2DS2-VASc(4.5 ± 1.3 vs.3.0 ± 1.4;P < 0.001) and HAS-BLED scores(2.0 ± 1.0 vs.1.4 ± 1.0;P < 0.001).Overall,the dose of rivaroxaban was adequately prescribed in 83.4% of patients,but more frequently in the younger population(71.1% vs.89.1%;P = 0.039).After a mean follow-up of 2.2 ± 0.6 years,annual rates of stroke + systemic embolism + transient ischemic attack,MACE,cardiovascular death and major bleeding were 1.03%,1.24%,1.03% and 1.75%,respectively,in octogenarian patients.Except for progressive heart failure death and major bleeding,rates of outcomes in octogenarians were similar compared to younger patients.In octogenarians,the concomitant use of antiplatelet agents and non-severe dementia were independently associated with the development of ischemic stroke,whereas previous coronary revascularization and heart failure with MACE,and higher HAS-BLED score with major bleeding.Conclusions In clinical practice,around one third of patients taking rivaroxaban are octogenarians.These patients have many comorbidities and a high thromboembolic risk.Despite that,rates of adverse events remain low.Rivaroxaban is adequately prescribed in the majority of octogenarians.展开更多
Macronutrients serve as a source of energy for both gut microbiota and its host. An increase or decrease in macronutrients can either increase or decrease the composition of gut microbiota, leading to gut dysbiosis wh...Macronutrients serve as a source of energy for both gut microbiota and its host. An increase or decrease in macronutrients can either increase or decrease the composition of gut microbiota, leading to gut dysbiosis which has been implicated in many diseases state including non-communicable diseases. To achieve this, seven diets were formulated by restricting 60% of each macronutrient. These diets were fed on 42 albino rats (Wistar), divided into 7 groups of 6 rats each. Group 1 was fed on a normal laboratory chow diet (ND), group 2 received a fat-restricted diet (FRD), group 3 received a protein-restricted diet, (PFD), group 4 received a carbohydrate-restricted diet (CRD), group 5 received a protein and fat-restricted diet (PFRD), group 6 re-ceived a carbohydrate and fat-restricted diet (CFRD) and group 7 received a carbohydrate and protein-restricted diet (CPRD). Feed and water intake were given ad libitum and daily weight and food intake were recorded. The experiment went on for 4 weeks after which animals were sacrificed and intestinal content and blood were collected for analysis (gut microbial composition, glucose, insulin levels, serum lipid, and enzyme). Compared to the control group results showed a decrease in Bacteroides (40.50 - 14.00 CFU), HDL (68.20 - 40.40 mg/dl), and AST (66.62 - 64.74 U/L) in FRD. An increase in AST (66.6 - 69.43 U/L), Bifidobacterial (59.50 - 92.00 CFU) and decreased Bacteroides (40.5 - 19.5 CFU) for PRD was also recorded. CRD reduced Lactobacillus (73 - 33.5 CFU), total bacterial count (129 - 48 CFU), HDL (68.2 - 30.8 mg/dl), and cholesterol (121.44 - 88.65 mg/dl) whereas intestinal composition of E. coli (30.5 - 51.5 CFU) increased. PFRD increased Lactobacillus (73.00 - 102.5 CFU), Bifidobacterial (59.5 - 100 CFU), HDL (68.2 - 74.7 mg/dl), and Triglyceride (111.67 - 146.67 mg/dl) concentration. Meanwhile, a reduction in Bifidobacterial (59.5 - 41.5 CFU), and an increasing of AST (66.62 - 70.30 U/l) were recorded for CFRD. However, Bacteroides (40.5 69.5 CFU), LDL (30.95 - 41.98 mg/dl) increased and Bifidobacterial (59.5 - 38.00 CFU) and HDL (68.2 - 53.5 mg/dl) decreased for CPRD. This work, therefore, concludes that macronutrient restriction causes significant changes in serum marker and enzyme profile, and gut microbial composition which can cause gut dysbiosis and later on could expose the host to inflammatory diseases in the long run.展开更多
In this study, bacteriocinogenic Lactobacillus plantarum isolates capable of inhibiting food- and feed-borne filamentous fungi from the gastrointestinal tract (GIT) of broiler chicken were identified using 16S rRNA ge...In this study, bacteriocinogenic Lactobacillus plantarum isolates capable of inhibiting food- and feed-borne filamentous fungi from the gastrointestinal tract (GIT) of broiler chicken were identified using 16S rRNA gene sequencing and further evaluated for probiotic properties in vitro. Six potent lactobacilli were selected from one hundred and thirteen isolates for the present study based on their ability to inhibit both pathogenic bacteria and filamentous fungi. They were characterized using various physiological, biochemical and molecular methods. They were acetoin producers, homo fermentative, catalase-negative and producing racemic lactic acid (10 - 20 mM). All the six isolates exhibited varied sugar utilization and RAPD pattern, indicated their strain level genotypic variation. The 16S rRNA gene sequence and multiplex PCR analysis confirmed that these isolates were Lactobacillus plantarum. The isolates being resistant to low pH (2.0) and bile salt (0.6%) could survive in the gastrointestinal tract of host indicating their potential probiotic application. The isolates were non-pathogenic (γ-hemolytic) and exhibited resistance to antibiotics ciprofloxacin, nalidixic acid, norfloxacin, nitrofurantoin, colistin and streptomycin. They demonstrated strong autoaggregating phenotype ranging from 78% to 86% and showed 49% - 61% and 30% - 46% coaggregation with E. coli MTCC 728 and L. monocytogenes MTCC 657, respectively. The percentage of hydrophobicity ranged from 16% - 33% for all the isolates showing that surface was rather hydrophilic. They exhibited β-galactosidase activity ranging from 1036 - 1179 MU, bile salt hydrolase activity assisting to reduce serum cholesterol and produced the anti-Listerial bacteriocin. The strong inhibitory activity of these isolates against food spoilage molds and bacteria with probiotic properties indicates their potential application as food preservatives.展开更多
基金supported by the Natural Science Foundation of Heilongjiang Province of China,Outstanding Youth Foundation,No.YQ2022H003 (to DW)。
文摘N6-methyladenosine(m^(6)A), the most prevalent and conserved RNA modification in eukaryotic cells, profoundly influences virtually all aspects of mRNA metabolism. mRNA plays crucial roles in neural stem cell genesis and neural regeneration, where it is highly concentrated and actively involved in these processes. Changes in m^(6)A modification levels and the expression levels of related enzymatic proteins can lead to neurological dysfunction and contribute to the development of neurological diseases. Furthermore, the proliferation and differentiation of neural stem cells, as well as nerve regeneration, are intimately linked to memory function and neurodegenerative diseases. This paper presents a comprehensive review of the roles of m^(6)A in neural stem cell proliferation, differentiation, and self-renewal, as well as its implications in memory and neurodegenerative diseases. m^(6)A has demonstrated divergent effects on the proliferation and differentiation of neural stem cells. These observed contradictions may arise from the time-specific nature of m^(6)A and its differential impact on neural stem cells across various stages of development. Similarly, the diverse effects of m^(6)A on distinct types of memory could be attributed to the involvement of specific brain regions in memory formation and recall. Inconsistencies in m^(6)A levels across different models of neurodegenerative disease, particularly Alzheimer's disease and Parkinson's disease, suggest that these disparities are linked to variations in the affected brain regions. Notably, the opposing changes in m^(6)A levels observed in Parkinson's disease models exposed to manganese compared to normal Parkinson's disease models further underscore the complexity of m^(6)A's role in neurodegenerative processes. The roles of m^(6)A in neural stem cell proliferation, differentiation, and self-renewal, and its implications in memory and neurodegenerative diseases, appear contradictory. These inconsistencies may be attributed to the timespecific nature of m^(6)A and its varying effects on distinct brain regions and in different environments.
文摘Objective INF2 is a member of the formins family.Abnormal expression and regulation of INF2 have been associated with the progression of various tumors,but the expression and role of INF2 in hepatocellular carcinoma(HCC)remain unclear.HCC is a highly lethal malignant tumor.Given the limitations of traditional treatments,this study explored the expression level,clinical value and potential mechanism of INF2 in HCC in order to seek new therapeutic targets.Methods In this study,we used public databases to analyze the expression of INF2 in pan-cancer and HCC,as well as the impact of INF2 expression levels on HCC prognosis.Quantitative real time polymerase chain reaction(RT-qPCR),Western blot,and immunohistochemistry were used to detect the expression level of INF2 in liver cancer cells and human HCC tissues.The correlation between INF2 expression and clinical pathological features was analyzed using public databases and clinical data of human HCC samples.Subsequently,the effects of INF2 expression on the biological function and Drp1 phosphorylation of liver cancer cells were elucidated through in vitro and in vivo experiments.Finally,the predictive value and potential mechanism of INF2 in HCC were further analyzed through database and immunohistochemical experiments.Results INF2 is aberrantly high expression in HCC samples and the high expression of INF2 is correlated with overall survival,liver cirrhosis and pathological differentiation of HCC patients.The expression level of INF2 has certain diagnostic value in predicting the prognosis and pathological differentiation of HCC.In vivo and in vitro HCC models,upregulated expression of INF2 triggers the proliferation and migration of the HCC cell,while knockdown of INF2 could counteract this effect.INF2 in liver cancer cells may affect mitochondrial division by inducing Drp1 phosphorylation and mediate immune escape by up-regulating PD-L1 expression,thus promoting tumor progression.Conclusion INF2 is highly expressed in HCC and is associated with poor prognosis.High expression of INF2 may promote HCC progression by inducing Drp1 phosphorylation and up-regulation of PD-L1 expression,and targeting INF2 may be beneficial for HCC patients with high expression of INF2.
基金supported by the Heilongjiang Province Key Research and Development Plan Guidance Project[Grant No.GZ20220039]the Central Government Supports the Local College Reform and Development Fund Talent Training Project[Grant No.2020GSP16].
文摘Objectives:Epibrassinolide(EBR)is a steroid hormone with anti-tumor properties.Nevertheless,its potential to inhibit gastric cancer(GC)cells remains unknown.The aim of this research was to examine the effects of EBR on GC cells and to investigate the specific mechanism of EBR.Methods:A cell counting kit-8(CCK-8)assay was utilized to determine cell survival rates.The investigation of apoptosis,cell cycle progression,and reactive oxygen species(ROS)levels was performed using flow cytometry.To detect cell migration,a wound-healing assay was performed on AGS cells.Furthermore,western blotting assay was utilized to determine protein expression levels.Results:The CCK-8 assay demonstrated that EBR reduced the survival rates of AGS,KATO-3,and MKN-45 cells,while causing only minor toxicity to normal cells.The apoptosis assay indicated that EBR induced AGS cell apoptosis through a mitochondria-mediated pathway.Western blotting results demonstrated that EBR induced AGS cell apoptosis via mitogen-activated protein kinase(MAPK)/signal transducer and activator of transcription 3(STAT3)/nuclear factor kappa B(NF-κB)signaling pathway.Further,after treating AGS cells with EBR,the accumulation of intracellular ROS markedly increased.EBR also induced G2/M phase cell cycle arrest in AGS cells by downregulating phospho-protein kinase B(p-AKT),cyclin-dependent kinase 1/2(CDK1/2),and cyclin B1 expression levels,while simultaneously upregulating p21 and p27 expression levels.EBR inhibited AGS cell migration by downregulating p-AKT,phosphorylated-glycogen synthase kinase 3β(p-GSK-3β),andβ-catenin expression levels and upregulating E-cadherin expression levels.However,these effects were reversed by pretreatment with N-acetylcysteine(NAC).Conclusion:EBR regulates AGS cells by inducing apoptosis and G2/M phase arrest,while also inhibiting cell migration,all of which are mediated through ROS-mediated signaling pathways.Ultimately,these effects suggest a significant role for EBR in regulating cellular processes within AGS cells.
基金supported by the National Key R&D Program of China(2022YFA1302701)the National Natural Science Foundation of China(32030056 to M.Y.+4 种基金32241031 and 32171195 to S.L.)the scientific project of Beijing Life Science Academy(2023300CA0090)Tsinghua University Initiative Scientific Research Program(2023Z11DSZ001)the King Abdullah University of Science and Technology(KAUST)Office of Sponsored Research(OSR)under Award(OSR-2020-CRG9-4352)Office of Research Administration(ORA)under Award No.URF/1/4352-01-01,FCC/1/1976-44-01,FCC/1/1976-45-01,REI/1/5234-01-01,and REI/1/5414-01-01.
文摘Dear Editor,Pyruvate dehydrogenase complex(PDHc) is a large multienzyme assembly(Mr = 4–10 million Daltons) consisting of three essential components: pyruvate dehydrogenase(E1p), dihydrolipoyl transacetylase(E2p), and dihydrolipoyl dehydrogenase(E3). These three enzymes perform distinct functions sequentially to catalyze the oxidative decarboxylation of pyruvate with formation of nicotinamide adenine dinucleotide(NADH) and acetyl-coenzyme A(Patel and Roche, 1990).
文摘Country bean, Lablab purpureus (L.) is considered one of the most important leguminous crops, but their cultivation under drought stress condition encounters challenges. In this study, an experiment has been conducted among 30 genotypes under drought condition to explore morphological diversity of qualitative and quantitative, biochemical, molecular analysis. The study identified significant variations in eight traits among the genotypes examined, with phenotypic variance exceeding genotypic variance, indicating both genetic and environmental influences. High heritability and genetic advance were observed in primary, secondary, and tertiary branch lengths, suggesting these traits are likely controlled by additive gene effects, making them effective targets for selection. Principal component analysis identified three components that made a substantial contribution, accounting for approximately 73.06% of the overall quantitative variations. Among the quantitative traits, the highest coefficient of variation (CV%) has been found in number of flowers (55.05%). While number of primary branches, primary branch length, number of secondary branches, secondary branch length, number of tertiary branches, tertiary branch length has individually more than 20% of CV%. The genotypes have been grouped into three clusters based on quantitative traits. Analysis of protein reveals that the genotypes of DS28 and DS29 have higher protein content than other genotypes. Dehydrogenase responsive genotypes have been found on DS28 and DS29 from the molecular analysis. The results suggest that the genotypes DS28 and DS29 could contribute as genetic resource of high protein content and DREB responsive, and the eight quantitative traits of 30 genotypes could be used for further breeding programme.
基金supported by the National Key Research and Development Program of China(2022YFD2300300)the National Natural Science Foundation of China(41907072)+1 种基金the Scientific Research Foundation of Zhejiang A&F University,China(2022LFR003)the Jiangsu Agriculture Science and Technology Innovation Fund,China(CX(21)3007).
文摘Water-saving irrigation strategies can successfully alleviate methane emissions from rice fields,but significantly stimulate nitrous oxide(N_(2)O)emissions because of variations in soil oxygen level and redox potential.However,the relationship linking soil N_(2)O emissions to nitrogen functional genes during various fertilization treatments in water-saving paddy fields has rarely been investigated.Furthermore,the mitigation potential of organic fertilizer substitution on N_(2)O emissions and the microbial mechanism in rice fields must be further elucidated.Our study examined how soil N_(2)O emissions were affected by related functional microorganisms(ammonia-oxidizing archaea(AOA),ammonia-oxidizing bacteria(AOB),nirS,nirK and nosZ)to various fertilization treatments in a rice field in southeast China over two years.In this study,three fertilization regimes were applied to rice cultivation:a no nitrogen(N)(Control),an inorganic N(Ni),and an inorganic N with partial N substitution with organic manure(N_(i)+N_(o)).Over two rice-growing seasons,cumulative N_(2)O emissions averaged 0.47,4.62 and 4.08 kg ha^(−1)for the Control,Ni and N_(i)+N_(o)treatments,respectively.In comparison to the Ni treatment,the N_(i)+N_(o)fertilization regime considerably reduced soil N_(2)O emissions by 11.6%while maintaining rice yield,with a lower N_(2)O emission factor(EF)from fertilizer N of 0.95%.Nitrogen fertilization considerably raised the AOB,nirS,nirK and nosZ gene abundances,in comparison to the Control treatment.Moreover,the substitution of organic manure for inorganic N fertilizer significantly decreased AOB and nirS gene abundances and increased nosZ gene abundance.The AOB responded to N fertilization more sensitively than the AOA.Total N_(2)O emissions significantly correlated positively with AOB and nirS gene abundances while having a negative correlation with nosZ gene abundance and the nosZ/nirS ratio across N-fertilized plots.In summary,we conclude that organic manure substitution for inorganic N fertilizer decreased soil N_(2)O emissions primarily by changing the soil NO_(3)^(−)-N,pH and DOC levels,thus inhibiting the activities of ammonia oxidation in nitrification and nitrite reduction in denitrification,and strengthening N_(2)O reduction in denitrification from water-saving rice paddies.
基金supported by the National Natural Science Foundation of China(Grant Nos.81870467 and 82270717 to XL,and 81970673 to FC)China Postdoctoral Science Foundation(Grant No.2023M731630 to XZhang)Postgraduate Research and Practice Innovation Program of Jiangsu Province(Grant No.KYCX21_1588 to XZhou).
文摘Islet beta cells(β-cells)produce insulin in response to high blood glucose levels,which is essential for preserving glucose homeostasis.Voltage-gated ion channels inβ-cells,including Na+,K+,and Ca2+channels,aid in the release of insulin.The epithelial sodium channel alpha subunit(α-ENaC),a voltage-independent sodium ion channel,is also expressed in human pancreatic endocrine cells.However,there is no reported study on the function of ENaC in theβ-cells.In the current study,we found thatα-ENaC was expressed in human pancreatic glandule and pancreatic isletβ-cells.In the pancreas of db/db mice and high-fat diet-induced mice,and in mouse isletβ-cells(MIN6 cells)treated with palmitate,α-ENaC expression was increased.Whenα-ENaC was overexpressed in MIN6 cells,insulin content and glucose-induced insulin secretion were significantly reduced.On the other hand,palmitate injured isletβ-cells and suppressed insulin synthesis and secretion,but increasedα-ENaC expression in MIN6 cells.However,α-ENaC knockout(Scnn1a−/−)in MIN6 cells attenuatedβ-cell disorder induced by palmitate.Furthermore,α-ENaC regulated the ubiquitylation and degradation of sirtuin 2 inβ-cells.α-ENaC also modulatedβ-cell function in correlation with the inositol-requiring enzyme 1 alpha/X-box binding protein 1(IRE1α/XBP1)and protein kinase RNA-like endoplasmic reticulum kinase/C/EBP homologous protein(PERK/CHOP)endoplasmic reticulum stress pathways.These results suggest thatα-ENaC may play a novel role in insulin synthesis and secretion in theβ-cells,and the upregulation ofα-ENaC promotes isletβ-cell dysfunction.In conclusion,α-ENaC may be a key regulator involved in isletβ-cell damage and a potential therapeutic target for type 2 diabetes mellitus.
基金the National Natural Science Foundation of China (Grants 82170844 and 82270613)the Sichuan Science and Technology Program (Grants 2022YFH0045 and 2022YFH0102)+5 种基金the 111 Project (Grant B18035)the 1·3·5 project for Disciplines of Excellence at West China Hospital, Sichuan University (Grant ZYGD22007 and ZYJC21004)Ningbo Top Medical and Health Research Program (No.2023030514)Ningbo Medical and Health Brand Discipline (Grant No.PPXK2018–02)Ningbo Clinical Research Center for Otolaryngology Head and Neck Disease (Grant No.2022L005)the Ministry of Education, Singapore, (Grant MOE-000395-00) to LYC.
文摘Osteoporosis,a metabolic bone disease characterized by low bone mineral density and deterioration of bone microarchitecture,has led to a high risk of fatal osteoporotic fractures worldwide.Accumulating evidence has revealed that sexual dimorphism is a notable feature of osteoporosis,with sex-specific differences in epidemiology and pathogenesis.Specifically,females are more susceptible than males to osteoporosis,while males are more prone to disability or death from the disease.To date,sex chromosome abnormalities and steroid hormones have been proven to contribute greatly to sexual dimorphism in osteoporosis by regulating the functions of bone cells.Understanding the sex-specific differences in osteoporosis and its related complications is essential for improving treatment strategies tailored to women and men.This literature review focuses on the mechanisms underlying sexual dimorphism in osteoporosis,mainly in a population of aging patients,chronic glucocorticoid administration,and diabetes.Moreover,we highlight the implications of sexual dimorphism for developing therapeutics and preventive strategies and screening approaches tailored to women and men.Additionally,the challenges in translating bench research to bedside treatments and future directions to overcome these obstacles will be discussed.
基金support from the National Natural Science Foundation of China(projectNo.81970029)the Fundamental Research Funds for the Central Universities of China(TheEmergency Projects on COVID-19.project No.xzy032020042)。
文摘Coronavirus disease 2019(COVID-19)is a kind of viral pneumonia which is caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).The emergence of SARS-CoV-2 has been marked as the third introduction of a highly pathogenic coronavirus into the human population after the severe acute respiratory syndrome coronavirus(SARS-CoV)and the Middle East respiratory syndrome coro-navirus(MERS-CoV)in the twenty-first century.In this minireview,we provide a brief introduction of the general features of SARS-CoV-2 and discuss current knowledge of molecular immune pathogenesis,diagnosis and treatment of COVID-19 on the base of the present understanding of SARS-CoV and MERS-CoV infections,which may be helpful in offering novel insights and potential therapeutic targets for combating the SARS-CoV-2 infection.
基金supported by grant SDU2020 to Prof.Bente Finsen and Prof.Martin R.Larsen(COPING AD–Collaborative Project on the Interaction between Neurons and Glia in Alzheimer’s Disease)
文摘As a key contributor to memory storage, the synapse is one of the earliest affected neuronal components in Alzheimer＇s disease （AD）. Under physiological conditions, the synaptic con- nections between neurons undergo activity-dependent func- tional and morphological re-organisation. This dynamic, ＇plastic＇ neural ability critically depends on the structural integrity of the synapse. Thus, proteins that are implicated in preserving the organisation and dynamics of synaptic connections, including microtubules of the cytoskeleton and associated proteins, have attracted much focus for their involvement in the malfunction- ing AD synapse.
基金supported by the National Natural Science Foundation of China(No.81771020,81570927 and 81271092)Grant for Scientific and Technological Development Plan for Medical and Health in Shandong Province(2019WS341).
文摘Objectives:Deletion of Fscn2 gene in mice has been linked to progressive hearing loss and degeneration of cochlear cells.Cisplatin,an antitumor drug,can cause various side effects,including ototoxicity.The aim of this study was to investigate the effects of Fscn2 on cisplatin-induced hearing impairment in mice and to explore the possible mechanism.Methods:Two-week-old Fscn2^(+/+)mice and Fscn2^(−/−)mice were treated with two doses of cisplatin,with a 3-day recovery period in between.ABR(auditory evoked brain stem response)thresholds were measured and cochlear pathology was observed at 3 weeks of age.Results:Both Fscn2^(+/+)and Fscn2^(−/−)mice showed hearing loss under the effect of cisplatin,but the impairment was more severe in Fscn2^(−/−)mice.Further experiments showed that the percentages of outer hair cell(OHC)and spiral ganglion neuron(SGN)loss were significantly higher in cisplatin-treated Fscn2^(−/−)mice compared to Fscn2^(+/+)mice.Additionally,knockdown of Fscn2 in HEI-OC1 cells worsened cisplatin-induced cell apoptosis.Conclusion:FSCN2 mediates reduction of CDDP induced ototoxicity by inhibiting cell apoptosis.
基金supported by National Natural Science Foundation of China [Grant numbers: 82272868 and 82173180]the Foundation of Joint Funds for the Innovation of Science and Technology, Fujian Province (No. 2020Y9126)Fujian Provincial Health Technology Project [Grant number: 2020CXA049]。
文摘Wnt signaling are critical pathway involved in organ development, tumorigenesis, and cancer progression. WNT7A, a member of the Wnt family, remains poorly understood in terms of its role and the underlying molecular mechanisms it entails in head and neck squamous cell carcinoma (HNSCC). According to the Cancer Genome Atlas (TCGA), transcriptome sequencing data of HNSCC, the expression level of WNT7A in tumors was found to be higher than in adjacent normal tissues, which was validated using Real-time RT-PCR and immunohistochemistry. Unexpectedly, overexpression of WNT7A did not activate the canonical Wnt-β-catenin pathway in HNSCC. Instead, our findings suggested that WNT7A potentially activated the FZD7/JAK1/STAT3 signaling pathway, leading to enhanced cell proliferation, self-renewal, and resistance to apoptosis. Furthermore, in a patient-derived xenograft (PDX) tumor model, high expression of WNT7A and phosphorylated STAT3 was observed, which positively correlated with tumor progression.These findings underscore the significance of WNT7A in HNSCC progression and propose the targeting of key molecules within the FZD7/JAK1/STAT3 pathway as a promising strategy for precise treatment of HNSCC.
基金supported by the National Natural Science Foundation of China(32088101)National key Research and Development Program of China(2017YFC1700105,2021YFA1301603).
文摘Objective:To elucidate the biological basis of the heart qi deficiency(HQD)pattern,an in-depth understanding of which is essential for improving clinical herbal therapy.Methods: We predicted and characterized HQD pattern genes using the new strategy,TCM-HIN2Vec,which involves heterogeneous network embedding and transcriptomic experiments.First,a heterogeneous network of traditional Chinese medicine(TCM)patterns was constructed using public databases.Next,we predicted HQD pattern genes using a heterogeneous network-embedding algorithm.We then analyzed the functional characteristics of HQD pattern genes using gene enrichment analysis and examined gene expression levels using RNA-seq.Finally,we identified TCM herbs that demonstrated enriched interactions with HQD pattern genes via herbal enrichment analysis.Results: Our TCM-HIN2Vec strategy revealed that candidate genes associated with HQD pattern were significantly enriched in energy metabolism,signal transduction pathways,and immune processes.Moreover,we found that these candidate genes were significantly differentially expressed in the transcriptional profile of mice model with heart failure with a qi deficiency pattern.Furthermore,herbal enrichment analysis identified TCM herbs that demonstrated enriched interactions with the top 10 candidate genes and could potentially serve as drug candidates for treating HQD.Conclusion: Our results suggested that TCM-HIN2Vec is capable of not only accurately identifying HQD pattern genes,but also deciphering the basis of HQD pattern.Furthermore our finding indicated that TCM-HIN2Vec may be further expanded to develop other patterns,leading to a new approach aimed at elucidating general TCM patterns and developing precision medicine.
文摘In this letter,we comment on a recent publication by Mei et al,in the World Journal of Hepatology,investigating the hepatoprotective effects of the modified Xiaoyao San(MXS)formula in a male rat model of non-alcoholic steatohepatitis(NASH).The authors found that MXS treatment mitigated hepatic steatosis and inflam-mation in the NASH model,as evidenced by the reduction in lipid droplets(LDs),fibrosis markers and lipogenic factors.Interestingly,these hepatoprotective effects were associated with androgen upregulation(based on metabolomics analysis of male steroid hormone metabolites),adenosine 5’-monophosphate-activated protein kinase(AMPK)activation,and restoration of phosphatase and tensin homolog(PTEN)expression.However,the authors did not clearly discuss the relationships between MXS-induced hepatic steatosis reduction in the NASH model,and androgen upregulation,AMPK activation,and restoration of PTEN expression.This editorial emphasizes the reported mechanisms and explains how they act or interact with each other to reduce hepatic steatosis and inflammation in the NASH model.As a perspective,we propose additional mechanisms(such as autophagy/lipophagy activation in hepatocytes)for the clearance of LDs and suppression of hepatic steatosis by MXS in the NASH model.A proper understanding of the mechanisms of MXS-induced reduction of hepatic steatosis might help in the treatment of NASH and related diseases.
基金supported by the National Natural Science Foundation of China(project No.81970029)Fundamental Research Funds for the Central Universities of China(The Emergency Projects on COVID-19,xzy032020042)Qinnong Bank-XJTU special project for COVID-19(qnxjtu-12)。
文摘Coronavirus disease 2019(COVID-19)has been a pandemic for more than a year.With the expanding second wave of the pandemic in winter,the continuous evolution of SARS-CoV-2 has brought new issues,including the significance of virus mutations in infection and the detection of asymptomatic infection.In this review,we first introduced several major SARS-CoV-2 mutations since the COVID-19 outbreak and then mentioned the widely used molecular detection techniques to diagnose COVID-19,primarily focusing on their strengths and limitations.We further discussed the effects of viral genetic variation and asymptomatic infection on the molecular detection of SARS-CoV-2 infection.The review finally summarized useful insights into the molecular diagnosis of COVID-19 under the special situation being challenged by virus mutation and asymptomatic infection.
基金funded by National Natural Science Foundation of China(Grant Nos.:81930096 and 82274063).
文摘Allergic inflammation is closely related to the activation of mast cells(MCs),which is regulated by its intracellular Ca^(2+) plevel,but the intake and effects of the intracellular Ca^(2+) premain unclear.The Ca^(2+) pinflux is controlled by members of Ca^(2+) pchannels,among which calcium voltage-gated channel subunit alpha1 C(CaV1.2)is the most robust.This study aimed to reveal the role and underlying mechanism of MC CaV1.2 in allergic inflammation.We found that CaV1.2 participated in MC activation and allergic inflammation.Nimodipine(Nim),as a strong CaV1.2-specific antagonist,ameliorated allergic inflammation in mice.Further,CaV1.2 activation in MC was triggered by phosphatizing at its Ser1928 through protein kinase C(PKC),which calcium/calmodulin-dependent protein kinase II(CaMKII)catalyzed.Overexpression or knockdown of MC CaV1.2 influenced MC activation.Importantly,CaV1.2 expression in MC had detrimental effects,while its deficiency ameliorated allergic pulmonary inflammation.Results provide novel insights into CaV1.2 function and a potential drug target for controlling allergic inflammation.
文摘Background: Hepatocellular carcinoma (HCC) is the most common type of liver cancer and one of the leading causes of cancer-related death worldwide. Advanced HCC displays strong resistance to chemotherapy, and traditional chemotherapy drugs do not achieve satisfactory therapeutic efficacy. The delivery of therapeutic compounds to the target site is a major challenge in the treatment of many diseases. Objective: This study aims to evaluate activated charcoal nanoparticles as a drug delivery system for anticancer agents (Sorafenib and Doxorubicin) in Hepatocellular Cancer Stem Cells. Method: The percent efficiency of entrapment (% EE) of the doxorubicin and sorafenib entrapped onto the activated charcoal was obtained by determining the free doxorubicin and sorafenib concentration in the supernatant-prepared solutions. Then the characterizations of nanoparticles were formed by determination of the particle size distribution, zeta potential, and polydispersity index (PDI). The anticancer activity of activated Charcoal, Doxorubicin-ACNP, sorafenib-ACNP, free doxorubicin, and free sorafenib solutions was measured based on cell viability percentage in HepG2 cell lines (ATCC-CCL 75). In vitro RBC’s toxicity of Doxorubicin/sorafenib loaded charcoal was estimated by hemolysis percentage. Results: The synthesized Doxorubicin-ACNP and Sorafenib-ACNP were evaluated and their physiochemical properties were also examined. Essentially, the percent Efficiency of Entrapment (EE %) was found to be 87.5% and 82.66% for Doxorubicin-ACNP and Sorafenib-ACNP, respectively. The loading capacity was 34.78% and 24.31% for Doxorubicin-ACNP and Sorafenib-ACNP. Using the Dynamic Light scattering [DLS] for the determination of the hydrodynamic size and surface zeta potential, a narrow sample size distribution was obtained of (18, 68, and 190 nm for charcoal, 105, 255, and 712 nm for doxorubicin, and 91, 295, and 955 nm for sorafenib), respectively. A surface charge of −13.2, −15.6 and −17 was obtained for charcoal, doxorubicin/charcoal, and sorafenib/charcoal nanoparticles. The cytotoxic activity of Doxorubicin-ACNP and Sorafenib-ACNP was evaluated in-vitro against HepG2 cell lines and it was observed that Drug loaded ACNP improved anticancer activity when compared to Doxorubicin or Sorafenib alone. Moreover, testing the toxicity potential of DOX-ACNP and Sorafenib-ACNP showed a significant reduction in the hemolysis of red blood cells when compared to Doxorubicin and Sorafenib alone. Conclusion: In conclusion, it is notable to state that this study is regarded as the first to investigate the use of Activated charcoal for the loading of Doxorubicin and Sorafenib for further use in the arena of hepatocellular carcinoma. Doxorubicin-ACNP and Sorafenib-ACNP showed noteworthy anticancer activity along with a reduced potential of RBCs hemolysis rendering it as an efficacious carrier with a low toxicity potential.
文摘Objectives To analyze the clinical profile,adequacy of treatment with rivaroxaban and outcomes in octogenarians with atrial fibrillation(AF),taking rivaroxaban in clinical practice.Methods Observational and non-interventional study that included AF adults recruited from 79 Spanish centers,anticoagulated with rivaroxaban ≥ 6 months before being included.Data were analyzed according to age(≥ 80 vs.< 80 years) at baseline.Results Out of 1433 patients,453(31.6%) were octogenarians at baseline.Compared to younger patients,octogenarians had more comorbidities,higher CHA2DS2-VASc(4.5 ± 1.3 vs.3.0 ± 1.4;P < 0.001) and HAS-BLED scores(2.0 ± 1.0 vs.1.4 ± 1.0;P < 0.001).Overall,the dose of rivaroxaban was adequately prescribed in 83.4% of patients,but more frequently in the younger population(71.1% vs.89.1%;P = 0.039).After a mean follow-up of 2.2 ± 0.6 years,annual rates of stroke + systemic embolism + transient ischemic attack,MACE,cardiovascular death and major bleeding were 1.03%,1.24%,1.03% and 1.75%,respectively,in octogenarian patients.Except for progressive heart failure death and major bleeding,rates of outcomes in octogenarians were similar compared to younger patients.In octogenarians,the concomitant use of antiplatelet agents and non-severe dementia were independently associated with the development of ischemic stroke,whereas previous coronary revascularization and heart failure with MACE,and higher HAS-BLED score with major bleeding.Conclusions In clinical practice,around one third of patients taking rivaroxaban are octogenarians.These patients have many comorbidities and a high thromboembolic risk.Despite that,rates of adverse events remain low.Rivaroxaban is adequately prescribed in the majority of octogenarians.
文摘Macronutrients serve as a source of energy for both gut microbiota and its host. An increase or decrease in macronutrients can either increase or decrease the composition of gut microbiota, leading to gut dysbiosis which has been implicated in many diseases state including non-communicable diseases. To achieve this, seven diets were formulated by restricting 60% of each macronutrient. These diets were fed on 42 albino rats (Wistar), divided into 7 groups of 6 rats each. Group 1 was fed on a normal laboratory chow diet (ND), group 2 received a fat-restricted diet (FRD), group 3 received a protein-restricted diet, (PFD), group 4 received a carbohydrate-restricted diet (CRD), group 5 received a protein and fat-restricted diet (PFRD), group 6 re-ceived a carbohydrate and fat-restricted diet (CFRD) and group 7 received a carbohydrate and protein-restricted diet (CPRD). Feed and water intake were given ad libitum and daily weight and food intake were recorded. The experiment went on for 4 weeks after which animals were sacrificed and intestinal content and blood were collected for analysis (gut microbial composition, glucose, insulin levels, serum lipid, and enzyme). Compared to the control group results showed a decrease in Bacteroides (40.50 - 14.00 CFU), HDL (68.20 - 40.40 mg/dl), and AST (66.62 - 64.74 U/L) in FRD. An increase in AST (66.6 - 69.43 U/L), Bifidobacterial (59.50 - 92.00 CFU) and decreased Bacteroides (40.5 - 19.5 CFU) for PRD was also recorded. CRD reduced Lactobacillus (73 - 33.5 CFU), total bacterial count (129 - 48 CFU), HDL (68.2 - 30.8 mg/dl), and cholesterol (121.44 - 88.65 mg/dl) whereas intestinal composition of E. coli (30.5 - 51.5 CFU) increased. PFRD increased Lactobacillus (73.00 - 102.5 CFU), Bifidobacterial (59.5 - 100 CFU), HDL (68.2 - 74.7 mg/dl), and Triglyceride (111.67 - 146.67 mg/dl) concentration. Meanwhile, a reduction in Bifidobacterial (59.5 - 41.5 CFU), and an increasing of AST (66.62 - 70.30 U/l) were recorded for CFRD. However, Bacteroides (40.5 69.5 CFU), LDL (30.95 - 41.98 mg/dl) increased and Bifidobacterial (59.5 - 38.00 CFU) and HDL (68.2 - 53.5 mg/dl) decreased for CPRD. This work, therefore, concludes that macronutrient restriction causes significant changes in serum marker and enzyme profile, and gut microbial composition which can cause gut dysbiosis and later on could expose the host to inflammatory diseases in the long run.
文摘In this study, bacteriocinogenic Lactobacillus plantarum isolates capable of inhibiting food- and feed-borne filamentous fungi from the gastrointestinal tract (GIT) of broiler chicken were identified using 16S rRNA gene sequencing and further evaluated for probiotic properties in vitro. Six potent lactobacilli were selected from one hundred and thirteen isolates for the present study based on their ability to inhibit both pathogenic bacteria and filamentous fungi. They were characterized using various physiological, biochemical and molecular methods. They were acetoin producers, homo fermentative, catalase-negative and producing racemic lactic acid (10 - 20 mM). All the six isolates exhibited varied sugar utilization and RAPD pattern, indicated their strain level genotypic variation. The 16S rRNA gene sequence and multiplex PCR analysis confirmed that these isolates were Lactobacillus plantarum. The isolates being resistant to low pH (2.0) and bile salt (0.6%) could survive in the gastrointestinal tract of host indicating their potential probiotic application. The isolates were non-pathogenic (γ-hemolytic) and exhibited resistance to antibiotics ciprofloxacin, nalidixic acid, norfloxacin, nitrofurantoin, colistin and streptomycin. They demonstrated strong autoaggregating phenotype ranging from 78% to 86% and showed 49% - 61% and 30% - 46% coaggregation with E. coli MTCC 728 and L. monocytogenes MTCC 657, respectively. The percentage of hydrophobicity ranged from 16% - 33% for all the isolates showing that surface was rather hydrophilic. They exhibited β-galactosidase activity ranging from 1036 - 1179 MU, bile salt hydrolase activity assisting to reduce serum cholesterol and produced the anti-Listerial bacteriocin. The strong inhibitory activity of these isolates against food spoilage molds and bacteria with probiotic properties indicates their potential application as food preservatives.
