In the present study we investigated the impact of the combination of astragalin and rutin(CAR)on restoring gut-microbial dysbiosis and obesity and obesity related disorders.Randomized male C57BL/6J mice were experime...In the present study we investigated the impact of the combination of astragalin and rutin(CAR)on restoring gut-microbial dysbiosis and obesity and obesity related disorders.Randomized male C57BL/6J mice were experimentally divided into 5 groups and fed either a normal diet or a high-fat diet(HFD)for 16 weeks.Compared to vehicle treated group(HFD group),CAR could substantially improve selected gut microbiota abundance(Akkermansia,Lactobacillus,Bifidobacteria,Roseburia,Prevotella),reversed the Firmicutes/Bacteroidetes proportions,and inhibited the growth of Escherichia coli,Salmonella,and Klebsiella in obese mice.In addition,CAR-treated mice showed significantly increased total short-chain fatty acid production,reduced body weight gain,organs’weights,serum lipid profile(except HDL)and insulin resistance.The mRNA expressions of CCAAT/enhancer binding protein-α(C/EBP-α),sterol regulatory element-binding protein-1c(SREBP-1c),peroxisome proliferator-activated receptor-γ(PPAR-γ),acetyl-CoA carboxylase(ACC),adipocyte protein 2(aP2),and fatty acid synthase(FAS)were downregulated(P<0.05)and the protein expression of PPAR-γwas downregulated while adenosine 5’monophosphate-activated protein kinase(AMPK)was phosphorylated in CAR-treated HFD-fed mice compared to the HFD control group.Interestingly,CAR-treated HFD-fed mice showed significantly improved tissue architecture in the liver and fatty tissues.In conclusion,the findings suggest that CAR/Moringa oleifera may be beneficial in the treatment of insulin resistance and obesity disorders.展开更多
Background The primary differentially methylated regions(DMRs) which are maternally hypermethylated serve as imprinting control regions(ICRs) that drive monoallelic gene expression, and these ICRs have been investigat...Background The primary differentially methylated regions(DMRs) which are maternally hypermethylated serve as imprinting control regions(ICRs) that drive monoallelic gene expression, and these ICRs have been investigated due to their implications in mammalian development. Although a subset of genes has been identified as imprinted, in-depth comparative approach needs to be developed for identification of species-specific imprinted genes. Here, we examined DNA methylation status and allelic expression at the KBTBD6 locus across species and tissues and explored potential mechanisms of imprinting.Results Using whole-genome bisulfite sequencing and RNA-sequencing on parthenogenetic and normal porcine embryos, we identified a maternally hypermethylated DMR between the embryos at the KBTBD6 promoter Cp G island and paternal monoallelic expression of KBTBD6. Also, in analyzed domesticated mammals but not in humans, non-human primates and mice, the KBTBD6 promoter Cp G islands were methylated in oocytes and/or allelically methyl-ated in tissues, and monoallelic KBTBD6 expression was observed, indicating livestock-specific imprinting. Further analysis revealed that these Cp G islands were embedded within transcripts in porcine and bovine oocytes which coexisted with an active transcription mark and DNA methylation, implying the presence of transcription-dependent imprinting.Conclusions In this study, our comparative approach revealed an imprinted expression of the KBTBD6 gene in domesticated mammals, but not in humans, non-human primates, and mice which implicates species-specific evolution of genomic imprinting.展开更多
Hydrogel-based tissue-engineered skin has attracted increased attention due to its potential to restore the structural integrity and functionality of skin.However,the mechanical properties of hydrogel scaffolds and na...Hydrogel-based tissue-engineered skin has attracted increased attention due to its potential to restore the structural integrity and functionality of skin.However,the mechanical properties of hydrogel scaffolds and natural skin are substantially different.Here,we developed a polyvinyl alcohol(PVA)/acrylamide based interpenetrating network(IPN)hydrogel that was surface modified with polydopamine(PDA)and termed Dopa-gel.The Dopa-gel exhibited mechanical properties similar to native skin tissue and a superior ability to modulate paracrine functions.Furthermore,a tough scaffold with tensile resistance was fabricated using this hydrogel by three-dimensional printing.The results showed that the interpenetration of PVA,alginate,and polyacrylamide networks notably enhanced the mechanical properties of the hydrogel.Surface modification with PDA endowed the hydrogels with increased secretion of immunomodulatory and proangiogenic factors.In an in vivo model,Dopa-gel treatment accelerated wound closure,increased vascularization,and promoted a shift in macrophages from a proinflammatory M1 phenotype to a prohealing and anti-inflammatory M2 phenotype within the wound area.Mechanistically,the focal adhesion kinase(FAK)/extracellular signal-related kinase(ERK)signaling pathway may mediate the promotion of skin defect healing by increasing paracrine secretion via the Dopa-gel.Additionally,proangiogenic factors can be induced through Rho-associated kinase-2(ROCK-2)/vascular endothelial growth factor(VEGF)-mediated paracrine secretion under tensile stress conditions.Taken together,these findings suggest that the multifunctional Dopa-gel,which has good mechanical properties similar to those of native skin tissue and enhanced immunomodulatory and angiogenic properties,is a promising scaffold for skin tissue regeneration.展开更多
The impact of epigenetic modifications like DNA methylation on plant phenotypes has expanded the possibilities for crop development.DNA methylation plays a part in the regulation of both the chromatin structure and ge...The impact of epigenetic modifications like DNA methylation on plant phenotypes has expanded the possibilities for crop development.DNA methylation plays a part in the regulation of both the chromatin structure and gene expression,and the enzyme involved,DNA methyltransferase,executes the methylation process within the plant genome.By regulating crucial biological pathways,epigenetic changes actively contribute to the creation of the phenotype.Therefore,epigenome editing may assist in overcoming some of the drawbacks of genome editing,which can have minor off-target consequences and merely facilitate the loss of a gene’s function.These drawbacks include gene knockout,which can have such off-target effects.This review provides examples of several molecular characteristics of DNA methylation,as well as some plant physiological processes that are impacted by these epigenetic changes in the plants.We also discuss how DNA alterations might be used to improve crops and meet the demands of sustainable and environmentally-friendly farming.展开更多
Rheumatoid arthritis(RA)is a systemic autoimmune disease that is primarily manifested as synovitis and polyarticular opacity and typically leads to serious joint damage and irreversible disability,thus adversely affec...Rheumatoid arthritis(RA)is a systemic autoimmune disease that is primarily manifested as synovitis and polyarticular opacity and typically leads to serious joint damage and irreversible disability,thus adversely affecting locomotion ability and life quality.Consequently,good prognosis heavily relies on the early diagnosis and effective therapeutic monitoring of RA.Activatable fluorescent probes play vital roles in the detection and imaging of biomarkers for disease diagnosis and in vivo imaging.Herein,we review the fluorescent probes developed for the detection and imaging of RA biomarkers,namely reactive oxygen/nitrogen species(hypochlorous acid,peroxynitrite,hydroxyl radical,nitroxyl),pH,and cysteine,and address the related challenges and prospects to inspire the design of novel fluorescent probes and the improvement of their performance in RA studies.展开更多
Coronavirus disease 2019(COVID-19)infection caused by the severe acute respiratory syndrome coronavirus 2 virus,its symptoms,treatment,and post-COVID-19 effects have been a major focus of research since 2020.In additi...Coronavirus disease 2019(COVID-19)infection caused by the severe acute respiratory syndrome coronavirus 2 virus,its symptoms,treatment,and post-COVID-19 effects have been a major focus of research since 2020.In addition to respiratory symptoms,different clinical variants of the virus have been associated with dynamic symptoms and multiorgan diseases,including liver abnormalities.The release of cytokines by the activation of innate immune cells during viral infection and the high doses of drugs used for COVID-19 treatment are considered major drivers of liver injury in COVID-19 patients.The degree of hepatic inflammation in patients suffering from chronic liver disease and having COVID-19 could be severe and can be estimated through different liver chemistry abnormality markers.Gut microbiota influences liver chemistry through its metabolites.Gut dysbiosis during COVID-19 treatment can promote liver inflammation.Here,we highlighted the bidirectional association of liver physiology and gut microbiota(gut-liver axis)and its potential to manipulate drug-induced chemical abnormalities in the livers of COVID-19 patients.展开更多
The Betula genus contains pentacyclic triterpenoid betulin known for its environmental adaptation and medicinal properties.However,the mechanisms underlying betulin biosynthesis responding to climate change remain unc...The Betula genus contains pentacyclic triterpenoid betulin known for its environmental adaptation and medicinal properties.However,the mechanisms underlying betulin biosynthesis responding to climate change remain unclear.In this study,the role of epigenetic modification(DNA methylation) in betulin biosynthesis was examined and how climatic factors influence it.Whole-genome bisulfite sequencing was performed for greenhouse-grown Chinese white birch(Betula platyphylla Sukaczev) treated with DNA methylation inhibitor zebularine(ZEB) and a natural birch population in Northeast China.ZEB treatment significantly affected the CHH methylation level of transposable elements and betulin content in a hormesis dose-dependent manner.The methylation and expression of bHLH9,a key transcriptional factor controlling betulin biosynthesis,were also consistently affected by ZEB treatment as a hormetic dose-response.In the natural population,there was a positive correlation between promoter methylation of bHLH9 and summer precipitation,while winter temperature was negatively correlated.Thus climate-dependent methylation of bHLH9 regulates the expression of downstream genes involved in betulin biosynthesis.This study highlights the role of environmental signals to induce epigenetic changes that result in betulin production,possibly helping to develop resilient plants to combat ongoing climate change and enhance secondary metabolite production.展开更多
A long chain insect pheromone for subterranean termites, LC (Lignoceric Acid), was intercalated into the inorganic interlayer, ZLH (Zinc Layered Hydroxide), resulting in the formation of a new nanohybrid, labelled as ...A long chain insect pheromone for subterranean termites, LC (Lignoceric Acid), was intercalated into the inorganic interlayer, ZLH (Zinc Layered Hydroxide), resulting in the formation of a new nanohybrid, labelled as LCN (Lignocerate Nanohybrid). The formation of this inorganic-organic structure nanohybrid was synthesized by the co-precipitation method using ZnO (Zinc Oxide) as the starting material. The PXRD (Powder X-Ray Diffraction) results confirmed the intercalation process although the diffraction patterns of the resultant nanohybrid and the unbound pheromone were fairly similar but both have different basal spacings values. The FTIR (Fourier Transform Infrared) profiles and the chemical composition test supported the intercalation process with the percentage loading of LC into ZLH calculated to be 85%. The thermal stability of the free anion, LC was enhanced when it was transformed into LCN, increasing from 257 °C to 352 °C. The release of LC from the nanohybrid behaved in a sustained manner, governed by the pseudo-second order kinetic model with higher release of LC in sodium carbonate solution than the pH aqueous media. The synthesized nanohybrid was found to be safe for plant germination when the two seed types were successfully germinated in all the tested nanohybrid concentrations. However, the percentage seed germination and the radical seed length from the nanohybrid showed lower values compared to its counterpart anion, LC.展开更多
Bioterrorism has received a lot of attention in the first decade of this century. Biological agents are considered attractive weapons for bioterrorism as these are easy to obtain, comparatively inexpensive to produce ...Bioterrorism has received a lot of attention in the first decade of this century. Biological agents are considered attractive weapons for bioterrorism as these are easy to obtain, comparatively inexpensive to produce and exhibit widespread fear and panic than the actual potential of physical damage. Bacillus anthracis(B. anthracis), the etiologic agent of anthrax is a Gram positive, spore forming, non-motile bacterium. This is supposed to be one of the most potent BW agents because its spores are extremely resistant to natural conditions and can survive for several decades in the environment. B.anthracis spores enter the body through skin lesion(cutaneous anthrax), lungs(pulmonary anthrax), or gastrointestinal route(gastrointestinal anthrax) and germinate, giving rise to the vegetative form. Anthrax is a concern of public health also in many countries where agriculture is the main source of income including India. Anthrax has been associated with human history for a very long time and regained its popularity after Sept 2001 incidence in United States. The present review article describes the history, biology, life cycle, pathogenicity, virulence, epidemiology and potential of B. anthracis as biological weapon.展开更多
Objective:To investigate the antibacterial aclivily of marine actinobacteria against multidrug resistance Staphylococcus aureus(MDRSA).Methods:Fifty one actinobacterial strains were isolated from salt pans soil,costal...Objective:To investigate the antibacterial aclivily of marine actinobacteria against multidrug resistance Staphylococcus aureus(MDRSA).Methods:Fifty one actinobacterial strains were isolated from salt pans soil,costal area in Kothapattanam,Ongole,Andhra Pradesh.Primary screening was done using cross-streak method against MDRSA.The bioaclive compounds are extracted from efficient actinobacteria using solvent extraction.The antimicrobial activity of crude and solvent extracts was perfomied using Kirby-Bauer method.MIC for ethyl acetate extract was determined by modified agar well diffusion method.The potent actinobacteria are identified using Nonomura key,Shirling and Gottlieb 1966 with Bergey's manual of determinative bacteriology.Results:Among the fifty one isolates screened for antibacterial activity,SRB25were found efficient against MDRSA.The ethyl acetate extracts showed high inhibition against test organism.MIC test was performed with the ethyl acetate extract against MDRSA and found to be 1 000μg/mL.The isolaled actinobacteria are identified as Streptomyces sp with the help of Nonomura key.Conclusions:The current investigation reveals that the marine actinobacteria from salt pan environment can be able to produce new drug molecules against drug resistant microorganisms.展开更多
The process of carcinogenesis is tightly regulated by antioxidant enzymes and matrix degrading enzymes, namely, matrix metalloproteinases(MMPs). Degradation of extracellular matrix(ECM) proteins like collagen, proteog...The process of carcinogenesis is tightly regulated by antioxidant enzymes and matrix degrading enzymes, namely, matrix metalloproteinases(MMPs). Degradation of extracellular matrix(ECM) proteins like collagen, proteoglycan, laminin, elastin and fibronectin is considered to be the prerequisite for tumor invasion and metastasis. MMPs can degrade essentially all of the ECM components and, most MMPs also substantially contribute to angiogenesis, differentiation, proliferation and apoptosis. Hence, MMPs are important regulators of tumor growth both at the primary site and in distant metastases; thus the enzymes are considered as important targets for cancer therapy. The implications of MMPs in cancers are no longer mysterious; however, the mechanism of action is yet to be explained. Herein, our major interest is to clarify how MMPs are tied up with gastrointestinal cancers. Gastrointestinal cancer is a variety of cancer types, including the cancers of gastrointestinal tract and organs, i.e., esophagus, stomach, biliary system, pancreas, small intestine, large intestine, rectum and anus. The activity of MMPs is regulated by its endogenous inhibitor tissue inhibitor of metallopro-teinase(TIMP) which bind MMPs with a 1:1 stoichiometry. In addition, RECK(reversion including cysteinerich protein with kazal motifs) is a membrane bound glycoprotein that inhibits MMP-2,-9 and-14. Moreover, α2-macroglobulin mediates the uptake of several MMPs thereby inhibit their activity. Cancerous conditions increase intrinsic reactive oxygen species(ROS) through mitochondrial dysfunction leading to altered protease/anti-protease balance. ROS, an index of oxidative stress is also involved in tumorigenesis by activation of different MAP kinase pathways including MMP induction. Oxidative stress is involved in cancer by changing the activity and expression of regulatory proteins especially MMPs. Epidemiological studies have shown that high intake of fruits that rich in antioxidants is associated with a lower cancer incidence. Evidence indicates that some antioxidants inhibit the growth of malignant cells by inducing apoptosis and inhibiting the activity of MMPs. This review is discussed in six subchapters, as follows.展开更多
AIM: To examine the effect of doxycycline on the activity of matrix metalloproteinases (MMPs) and oxidative stress in gastric tissues of rats following gastric injury.METHODS: Gastric ulcers were generated in rats by ...AIM: To examine the effect of doxycycline on the activity of matrix metalloproteinases (MMPs) and oxidative stress in gastric tissues of rats following gastric injury.METHODS: Gastric ulcers were generated in rats by administration of 70% ethanol,and activity of doxycycline was tested by administration 30 min prior to ethanol.Similarly,the effect of doxycycline was tested in an indomethacin-induced gastric ulcer model.The activities and expression of MMPs were examined by zymography and Western blot analysis.RESULTS: Gastric injury in rats as judged by elevated ulcer indices following exposure to ulcerogen,either indomethacin or ethanol,was reversed significantly by doxycycline.Indomethacin-induced ulcerated gastric tissues exhibited about 12-fold higher proMMP-9 activity and about 5-fold higher proMMP-3 activity as compared to control tissues.Similarly,ethanol induced about 22-fold and about 6-fold higher proMMP-9 and proMMP-3 activities,respectively,in rat gastric tissues.Both proMMP-9 and MMP-3 activities were markedly decreased by doxycycline in ulcerogen treated rat gastric tissues.In contrast,the reduced MMP-2 activity in ulcerated tissues was increased by doxycycline during ulcer prevention.On the other hand,doxycycline inhibited significantly proMMP-9,-2 and -3 activities in vitro.In addition,doxycycline reduced oxidative load in gastric tissues and scavenged H2O2 in vitro.Our results suggest a novel regulatory role of doxycycline on MMP-2 activity in addition to inhibitory action on MMP-9 and MMP-3 during prevention of gastric ulcers.CONCLUSION: This is the first demonstration of dual action of doxycycline,that is,regulation of MMP activity and reduction of oxidative stress in arresting gastric injury.展开更多
Further improvement of rice productivity remains a challenge. Breeding is perceived as an important option to increase rice yield. However, the genetic progress of grain yield in most rice breeding programs was slow i...Further improvement of rice productivity remains a challenge. Breeding is perceived as an important option to increase rice yield. However, the genetic progress of grain yield in most rice breeding programs was slow in the last decades. Although great progress in rice genomics and molecular biology has been achieved, the effect of such technological innovations on rice breeding is far small. Marker-assisted selection （MAS） for a few target quantitative trait loci （QTLs） has significant effects in improving qualitative traits, such as disease resistance. The success of MAS has therefore motivated breeders to identify and use major QTLs for yield and yield component traits. In this review, we summarized the recent methods in QTL identification, including novel statistical methods for linkage and association mapping, special population types, and whole-genome sequencing. We reviewed the successful application of marker-assisted gene introgression and gene pyramiding to improve grain yield and discussed the design of efficient MAS schemes to further increase the success rate of breeding programs. The use of well-characterized major QTLs through introgression and gene pyramiding is proven effective in improving grain yield, particularly yield under abiotic stress. Major QTLs that are stable across genetic background and growing environments are often found in less adapted germplasms, such as landraces and wild relatives. Advanced backcross QTL analysis and introgression lines, which integrate QTL discovery and utilization, are important methods for exploiting major QTLs contained in such germplasms. Next-generation sequencing substantially increases mapping resolution and accelerates the identification of casual genes underlying major QTLs. Practical guidelines derived from theoretical and empirical studies are given to guide the design of efficient marker-assisted gene introgression and pyramiding schemes.展开更多
Chronic hepatitis C virus(HCV) infection is a public health issue that often progresses to life-threatening complications, including liver cirrhosis, fibrosis, and hepatocellular carcinoma. Impaired immune responses t...Chronic hepatitis C virus(HCV) infection is a public health issue that often progresses to life-threatening complications, including liver cirrhosis, fibrosis, and hepatocellular carcinoma. Impaired immune responses to HCV are key features of chronic HCV infection. Therefore, intervention strategies usually involve enhancing the immune responses against HCV. Cytotoxic CD8+ T lymphocytes(CTLs) play a critical role in the control of HCV infection. However, their cytolytic function can be impaired by the expression of co-inhibitory molecules. Programmed death-1(PD-1) receptor and its ligand PD-L1 function in a T cell co-inhibitory pathway, which either blocks the function of CTLs or the differentiation of CD8+ T cells. During chronic HCV infection, the immune inhibitory receptor PD-1 is upregulated on dysfunctional HCV-specific CD8+ T cells. As such, blockade of the PD-1/PD-L1 pathway in these CD8+ T cells might restore their functional capabilities. Indeed, clinical trials using therapies to block this pathway have shown promise in the fostering of anti-HCV immunity. Understanding how chronic HCV infection induces upregulation of PD-1 on HCV specific T cells and how the PD-1/PD-L1 interaction develops HCV specific T cell dysfunction will accelerate the development of an efficacious prophylactic and therapeutic vaccination against chronic HCV infections, which will significantly improve HCV treatments and patient survival. In this review, we discuss the relationship between PD-1 expression and clinical responses and the potential use of PD-1 blockade for anti-HCV therapy.展开更多
Hepatitis C virus(HCV) is endemic in Pakistan and its burden is expected to increase in coming decades owing mainly to widespread use of unsafe medical procedures. The prevalence of HCV in Pakistan has previously been...Hepatitis C virus(HCV) is endemic in Pakistan and its burden is expected to increase in coming decades owing mainly to widespread use of unsafe medical procedures. The prevalence of HCV in Pakistan has previously been reviewed. However, the literature search conducted here revealed that at least 86 relevant studies have been produced since the publication of these systematic reviews. A revised updated analysis was therefore needed in order to integrate the fresh data. A systematic review of data published between 2010 and 2015 showed that HCV seroprevalence among the general adult Pakistani population is 6.8%, while active HCV infection was found in approximately 6% of the population. Studies included in this review have also shown extremely high HCV prevalence in rural and underdeveloped peri-urban areas(up to 25%), highlighting the need for an increased focus on this previously neglected socioeconomic stratum of the population. While a 2.45% seroprevalence among blood donors demands immediate measures to curtail the risk of transfusion transmitted HCV, a very high prevalence in patients attending hospitals with various non-liver disease related complaints(up to 30%) suggests a rise in the incidence of nosocomial HCV spread. HCV genotype 3a continues to be the most prevalent subtype infecting people in Pakistan(61.3%). However, recent years have witnessed an increase in the frequency of subtype 2a in certain geographical sub-regions within Pakistan. In Khyber Pakhtunkhwa and Sindh provinces, 2a was the second most prevalent genotype(17.3% and 11.3% respectively). While the changing frequency distribution of various genotypes demands an increased emphasis on research for novel therapeutic regimens, evidence of high nosocomial transmission calls for immediate measures aimed at ensuring safe medical practices.展开更多
基金Authors are grateful to the Department of Science and Technology,New Delhi,for financial support(DST-SERB,EEQ/2016/000123,2016-17),and thank DST-FIST,Department of Biochemistry,S.V.University.
文摘In the present study we investigated the impact of the combination of astragalin and rutin(CAR)on restoring gut-microbial dysbiosis and obesity and obesity related disorders.Randomized male C57BL/6J mice were experimentally divided into 5 groups and fed either a normal diet or a high-fat diet(HFD)for 16 weeks.Compared to vehicle treated group(HFD group),CAR could substantially improve selected gut microbiota abundance(Akkermansia,Lactobacillus,Bifidobacteria,Roseburia,Prevotella),reversed the Firmicutes/Bacteroidetes proportions,and inhibited the growth of Escherichia coli,Salmonella,and Klebsiella in obese mice.In addition,CAR-treated mice showed significantly increased total short-chain fatty acid production,reduced body weight gain,organs’weights,serum lipid profile(except HDL)and insulin resistance.The mRNA expressions of CCAAT/enhancer binding protein-α(C/EBP-α),sterol regulatory element-binding protein-1c(SREBP-1c),peroxisome proliferator-activated receptor-γ(PPAR-γ),acetyl-CoA carboxylase(ACC),adipocyte protein 2(aP2),and fatty acid synthase(FAS)were downregulated(P<0.05)and the protein expression of PPAR-γwas downregulated while adenosine 5’monophosphate-activated protein kinase(AMPK)was phosphorylated in CAR-treated HFD-fed mice compared to the HFD control group.Interestingly,CAR-treated HFD-fed mice showed significantly improved tissue architecture in the liver and fatty tissues.In conclusion,the findings suggest that CAR/Moringa oleifera may be beneficial in the treatment of insulin resistance and obesity disorders.
基金partially supported by the United States Department of Agriculture National Institute of Food and Agriculture Hatch Grant (Project No.OHO01304)。
文摘Background The primary differentially methylated regions(DMRs) which are maternally hypermethylated serve as imprinting control regions(ICRs) that drive monoallelic gene expression, and these ICRs have been investigated due to their implications in mammalian development. Although a subset of genes has been identified as imprinted, in-depth comparative approach needs to be developed for identification of species-specific imprinted genes. Here, we examined DNA methylation status and allelic expression at the KBTBD6 locus across species and tissues and explored potential mechanisms of imprinting.Results Using whole-genome bisulfite sequencing and RNA-sequencing on parthenogenetic and normal porcine embryos, we identified a maternally hypermethylated DMR between the embryos at the KBTBD6 promoter Cp G island and paternal monoallelic expression of KBTBD6. Also, in analyzed domesticated mammals but not in humans, non-human primates and mice, the KBTBD6 promoter Cp G islands were methylated in oocytes and/or allelically methyl-ated in tissues, and monoallelic KBTBD6 expression was observed, indicating livestock-specific imprinting. Further analysis revealed that these Cp G islands were embedded within transcripts in porcine and bovine oocytes which coexisted with an active transcription mark and DNA methylation, implying the presence of transcription-dependent imprinting.Conclusions In this study, our comparative approach revealed an imprinted expression of the KBTBD6 gene in domesticated mammals, but not in humans, non-human primates, and mice which implicates species-specific evolution of genomic imprinting.
基金supported by the National Natural Science Foundation of China(32271413 and 32271408)the National Basic Research Program of China(2021YFA1201404)+2 种基金the Natural Science Foundation of Jiangsu Province(BK20232023)the Science Program of Jiangsu Province Administration for Market Regulation(KJ2024010)the Jiangsu Provincial Key Medical Center Foundation,and the Jiangsu Provincial Medical Outstanding Talent Foundation.
文摘Hydrogel-based tissue-engineered skin has attracted increased attention due to its potential to restore the structural integrity and functionality of skin.However,the mechanical properties of hydrogel scaffolds and natural skin are substantially different.Here,we developed a polyvinyl alcohol(PVA)/acrylamide based interpenetrating network(IPN)hydrogel that was surface modified with polydopamine(PDA)and termed Dopa-gel.The Dopa-gel exhibited mechanical properties similar to native skin tissue and a superior ability to modulate paracrine functions.Furthermore,a tough scaffold with tensile resistance was fabricated using this hydrogel by three-dimensional printing.The results showed that the interpenetration of PVA,alginate,and polyacrylamide networks notably enhanced the mechanical properties of the hydrogel.Surface modification with PDA endowed the hydrogels with increased secretion of immunomodulatory and proangiogenic factors.In an in vivo model,Dopa-gel treatment accelerated wound closure,increased vascularization,and promoted a shift in macrophages from a proinflammatory M1 phenotype to a prohealing and anti-inflammatory M2 phenotype within the wound area.Mechanistically,the focal adhesion kinase(FAK)/extracellular signal-related kinase(ERK)signaling pathway may mediate the promotion of skin defect healing by increasing paracrine secretion via the Dopa-gel.Additionally,proangiogenic factors can be induced through Rho-associated kinase-2(ROCK-2)/vascular endothelial growth factor(VEGF)-mediated paracrine secretion under tensile stress conditions.Taken together,these findings suggest that the multifunctional Dopa-gel,which has good mechanical properties similar to those of native skin tissue and enhanced immunomodulatory and angiogenic properties,is a promising scaffold for skin tissue regeneration.
文摘The impact of epigenetic modifications like DNA methylation on plant phenotypes has expanded the possibilities for crop development.DNA methylation plays a part in the regulation of both the chromatin structure and gene expression,and the enzyme involved,DNA methyltransferase,executes the methylation process within the plant genome.By regulating crucial biological pathways,epigenetic changes actively contribute to the creation of the phenotype.Therefore,epigenome editing may assist in overcoming some of the drawbacks of genome editing,which can have minor off-target consequences and merely facilitate the loss of a gene’s function.These drawbacks include gene knockout,which can have such off-target effects.This review provides examples of several molecular characteristics of DNA methylation,as well as some plant physiological processes that are impacted by these epigenetic changes in the plants.We also discuss how DNA alterations might be used to improve crops and meet the demands of sustainable and environmentally-friendly farming.
基金supported by the National Natural Science Foundation of China(82072432)the China-Japan Friendship Hospital Horizontal Project/Spontaneous Research Funding(2022-HX-JC-7)+1 种基金the National High Level Hospital Clinical Research Funding(2022-NHLHCRF-PY-20)the Elite Medical Professionals project of China-Japan Friendship Hospital(ZRJY2021-GG12).
文摘Rheumatoid arthritis(RA)is a systemic autoimmune disease that is primarily manifested as synovitis and polyarticular opacity and typically leads to serious joint damage and irreversible disability,thus adversely affecting locomotion ability and life quality.Consequently,good prognosis heavily relies on the early diagnosis and effective therapeutic monitoring of RA.Activatable fluorescent probes play vital roles in the detection and imaging of biomarkers for disease diagnosis and in vivo imaging.Herein,we review the fluorescent probes developed for the detection and imaging of RA biomarkers,namely reactive oxygen/nitrogen species(hypochlorous acid,peroxynitrite,hydroxyl radical,nitroxyl),pH,and cysteine,and address the related challenges and prospects to inspire the design of novel fluorescent probes and the improvement of their performance in RA studies.
基金Supported by United Arab Emirates University UPAR 2022 Research Grant,No.12S094.
文摘Coronavirus disease 2019(COVID-19)infection caused by the severe acute respiratory syndrome coronavirus 2 virus,its symptoms,treatment,and post-COVID-19 effects have been a major focus of research since 2020.In addition to respiratory symptoms,different clinical variants of the virus have been associated with dynamic symptoms and multiorgan diseases,including liver abnormalities.The release of cytokines by the activation of innate immune cells during viral infection and the high doses of drugs used for COVID-19 treatment are considered major drivers of liver injury in COVID-19 patients.The degree of hepatic inflammation in patients suffering from chronic liver disease and having COVID-19 could be severe and can be estimated through different liver chemistry abnormality markers.Gut microbiota influences liver chemistry through its metabolites.Gut dysbiosis during COVID-19 treatment can promote liver inflammation.Here,we highlighted the bidirectional association of liver physiology and gut microbiota(gut-liver axis)and its potential to manipulate drug-induced chemical abnormalities in the livers of COVID-19 patients.
基金the National Non-profi t Institute Research Grant of the Chinese Academy of Forestry(CAFYBB2019ZY003)the National Natural Science Foundation of China(31871220 and 31801444)+2 种基金the Innovation Project of State Key Laboratory of Tree Genetics andBreeding(Northeast Forestry University)(2013A06)the Fundamental Research Funds for the Central Universities(2572017DA06 and 2572020DP01)Heilongjiang Provincial Natural Science Foundation of China(LH2021C005).
文摘The Betula genus contains pentacyclic triterpenoid betulin known for its environmental adaptation and medicinal properties.However,the mechanisms underlying betulin biosynthesis responding to climate change remain unclear.In this study,the role of epigenetic modification(DNA methylation) in betulin biosynthesis was examined and how climatic factors influence it.Whole-genome bisulfite sequencing was performed for greenhouse-grown Chinese white birch(Betula platyphylla Sukaczev) treated with DNA methylation inhibitor zebularine(ZEB) and a natural birch population in Northeast China.ZEB treatment significantly affected the CHH methylation level of transposable elements and betulin content in a hormesis dose-dependent manner.The methylation and expression of bHLH9,a key transcriptional factor controlling betulin biosynthesis,were also consistently affected by ZEB treatment as a hormetic dose-response.In the natural population,there was a positive correlation between promoter methylation of bHLH9 and summer precipitation,while winter temperature was negatively correlated.Thus climate-dependent methylation of bHLH9 regulates the expression of downstream genes involved in betulin biosynthesis.This study highlights the role of environmental signals to induce epigenetic changes that result in betulin production,possibly helping to develop resilient plants to combat ongoing climate change and enhance secondary metabolite production.
文摘A long chain insect pheromone for subterranean termites, LC (Lignoceric Acid), was intercalated into the inorganic interlayer, ZLH (Zinc Layered Hydroxide), resulting in the formation of a new nanohybrid, labelled as LCN (Lignocerate Nanohybrid). The formation of this inorganic-organic structure nanohybrid was synthesized by the co-precipitation method using ZnO (Zinc Oxide) as the starting material. The PXRD (Powder X-Ray Diffraction) results confirmed the intercalation process although the diffraction patterns of the resultant nanohybrid and the unbound pheromone were fairly similar but both have different basal spacings values. The FTIR (Fourier Transform Infrared) profiles and the chemical composition test supported the intercalation process with the percentage loading of LC into ZLH calculated to be 85%. The thermal stability of the free anion, LC was enhanced when it was transformed into LCN, increasing from 257 °C to 352 °C. The release of LC from the nanohybrid behaved in a sustained manner, governed by the pseudo-second order kinetic model with higher release of LC in sodium carbonate solution than the pH aqueous media. The synthesized nanohybrid was found to be safe for plant germination when the two seed types were successfully germinated in all the tested nanohybrid concentrations. However, the percentage seed germination and the radical seed length from the nanohybrid showed lower values compared to its counterpart anion, LC.
基金Defence Research and Development Establishment,Defence Research and Development Organization,Ministry of Defence,Gwalior
文摘Bioterrorism has received a lot of attention in the first decade of this century. Biological agents are considered attractive weapons for bioterrorism as these are easy to obtain, comparatively inexpensive to produce and exhibit widespread fear and panic than the actual potential of physical damage. Bacillus anthracis(B. anthracis), the etiologic agent of anthrax is a Gram positive, spore forming, non-motile bacterium. This is supposed to be one of the most potent BW agents because its spores are extremely resistant to natural conditions and can survive for several decades in the environment. B.anthracis spores enter the body through skin lesion(cutaneous anthrax), lungs(pulmonary anthrax), or gastrointestinal route(gastrointestinal anthrax) and germinate, giving rise to the vegetative form. Anthrax is a concern of public health also in many countries where agriculture is the main source of income including India. Anthrax has been associated with human history for a very long time and regained its popularity after Sept 2001 incidence in United States. The present review article describes the history, biology, life cycle, pathogenicity, virulence, epidemiology and potential of B. anthracis as biological weapon.
基金financial support for the completion of this work
文摘Objective:To investigate the antibacterial aclivily of marine actinobacteria against multidrug resistance Staphylococcus aureus(MDRSA).Methods:Fifty one actinobacterial strains were isolated from salt pans soil,costal area in Kothapattanam,Ongole,Andhra Pradesh.Primary screening was done using cross-streak method against MDRSA.The bioaclive compounds are extracted from efficient actinobacteria using solvent extraction.The antimicrobial activity of crude and solvent extracts was perfomied using Kirby-Bauer method.MIC for ethyl acetate extract was determined by modified agar well diffusion method.The potent actinobacteria are identified using Nonomura key,Shirling and Gottlieb 1966 with Bergey's manual of determinative bacteriology.Results:Among the fifty one isolates screened for antibacterial activity,SRB25were found efficient against MDRSA.The ethyl acetate extracts showed high inhibition against test organism.MIC test was performed with the ethyl acetate extract against MDRSA and found to be 1 000μg/mL.The isolaled actinobacteria are identified as Streptomyces sp with the help of Nonomura key.Conclusions:The current investigation reveals that the marine actinobacteria from salt pan environment can be able to produce new drug molecules against drug resistant microorganisms.
基金Supported by Council of Scientific and Industrial Research,India(CSIR)-INDEPTH and HUM projects
文摘The process of carcinogenesis is tightly regulated by antioxidant enzymes and matrix degrading enzymes, namely, matrix metalloproteinases(MMPs). Degradation of extracellular matrix(ECM) proteins like collagen, proteoglycan, laminin, elastin and fibronectin is considered to be the prerequisite for tumor invasion and metastasis. MMPs can degrade essentially all of the ECM components and, most MMPs also substantially contribute to angiogenesis, differentiation, proliferation and apoptosis. Hence, MMPs are important regulators of tumor growth both at the primary site and in distant metastases; thus the enzymes are considered as important targets for cancer therapy. The implications of MMPs in cancers are no longer mysterious; however, the mechanism of action is yet to be explained. Herein, our major interest is to clarify how MMPs are tied up with gastrointestinal cancers. Gastrointestinal cancer is a variety of cancer types, including the cancers of gastrointestinal tract and organs, i.e., esophagus, stomach, biliary system, pancreas, small intestine, large intestine, rectum and anus. The activity of MMPs is regulated by its endogenous inhibitor tissue inhibitor of metallopro-teinase(TIMP) which bind MMPs with a 1:1 stoichiometry. In addition, RECK(reversion including cysteinerich protein with kazal motifs) is a membrane bound glycoprotein that inhibits MMP-2,-9 and-14. Moreover, α2-macroglobulin mediates the uptake of several MMPs thereby inhibit their activity. Cancerous conditions increase intrinsic reactive oxygen species(ROS) through mitochondrial dysfunction leading to altered protease/anti-protease balance. ROS, an index of oxidative stress is also involved in tumorigenesis by activation of different MAP kinase pathways including MMP induction. Oxidative stress is involved in cancer by changing the activity and expression of regulatory proteins especially MMPs. Epidemiological studies have shown that high intake of fruits that rich in antioxidants is associated with a lower cancer incidence. Evidence indicates that some antioxidants inhibit the growth of malignant cells by inducing apoptosis and inhibiting the activity of MMPs. This review is discussed in six subchapters, as follows.
基金Supported by Research Fellowship from Council of Scientific and Industrial Research,New Delhi,No.NBA2007 of DBT,IAP001 and CLP 261 of NTRF
文摘AIM: To examine the effect of doxycycline on the activity of matrix metalloproteinases (MMPs) and oxidative stress in gastric tissues of rats following gastric injury.METHODS: Gastric ulcers were generated in rats by administration of 70% ethanol,and activity of doxycycline was tested by administration 30 min prior to ethanol.Similarly,the effect of doxycycline was tested in an indomethacin-induced gastric ulcer model.The activities and expression of MMPs were examined by zymography and Western blot analysis.RESULTS: Gastric injury in rats as judged by elevated ulcer indices following exposure to ulcerogen,either indomethacin or ethanol,was reversed significantly by doxycycline.Indomethacin-induced ulcerated gastric tissues exhibited about 12-fold higher proMMP-9 activity and about 5-fold higher proMMP-3 activity as compared to control tissues.Similarly,ethanol induced about 22-fold and about 6-fold higher proMMP-9 and proMMP-3 activities,respectively,in rat gastric tissues.Both proMMP-9 and MMP-3 activities were markedly decreased by doxycycline in ulcerogen treated rat gastric tissues.In contrast,the reduced MMP-2 activity in ulcerated tissues was increased by doxycycline during ulcer prevention.On the other hand,doxycycline inhibited significantly proMMP-9,-2 and -3 activities in vitro.In addition,doxycycline reduced oxidative load in gastric tissues and scavenged H2O2 in vitro.Our results suggest a novel regulatory role of doxycycline on MMP-2 activity in addition to inhibitory action on MMP-9 and MMP-3 during prevention of gastric ulcers.CONCLUSION: This is the first demonstration of dual action of doxycycline,that is,regulation of MMP activity and reduction of oxidative stress in arresting gastric injury.
基金supported by the National Natural Science Foundation of China(Grant Nos.31221004 and 31271700)National Basic Research Program of China(Grant No.2013CBA01405)the Chinese 863 Program(Grant No.2012AA10A302)
文摘Further improvement of rice productivity remains a challenge. Breeding is perceived as an important option to increase rice yield. However, the genetic progress of grain yield in most rice breeding programs was slow in the last decades. Although great progress in rice genomics and molecular biology has been achieved, the effect of such technological innovations on rice breeding is far small. Marker-assisted selection （MAS） for a few target quantitative trait loci （QTLs） has significant effects in improving qualitative traits, such as disease resistance. The success of MAS has therefore motivated breeders to identify and use major QTLs for yield and yield component traits. In this review, we summarized the recent methods in QTL identification, including novel statistical methods for linkage and association mapping, special population types, and whole-genome sequencing. We reviewed the successful application of marker-assisted gene introgression and gene pyramiding to improve grain yield and discussed the design of efficient MAS schemes to further increase the success rate of breeding programs. The use of well-characterized major QTLs through introgression and gene pyramiding is proven effective in improving grain yield, particularly yield under abiotic stress. Major QTLs that are stable across genetic background and growing environments are often found in less adapted germplasms, such as landraces and wild relatives. Advanced backcross QTL analysis and introgression lines, which integrate QTL discovery and utilization, are important methods for exploiting major QTLs contained in such germplasms. Next-generation sequencing substantially increases mapping resolution and accelerates the identification of casual genes underlying major QTLs. Practical guidelines derived from theoretical and empirical studies are given to guide the design of efficient marker-assisted gene introgression and pyramiding schemes.
基金Supported by Science and Technology Development Fund(STDFgrants No.1469 and No.5245)Tanta University Fund,Egypt to Mohamed L Salem,the Principal investigator of these projects
文摘Chronic hepatitis C virus(HCV) infection is a public health issue that often progresses to life-threatening complications, including liver cirrhosis, fibrosis, and hepatocellular carcinoma. Impaired immune responses to HCV are key features of chronic HCV infection. Therefore, intervention strategies usually involve enhancing the immune responses against HCV. Cytotoxic CD8+ T lymphocytes(CTLs) play a critical role in the control of HCV infection. However, their cytolytic function can be impaired by the expression of co-inhibitory molecules. Programmed death-1(PD-1) receptor and its ligand PD-L1 function in a T cell co-inhibitory pathway, which either blocks the function of CTLs or the differentiation of CD8+ T cells. During chronic HCV infection, the immune inhibitory receptor PD-1 is upregulated on dysfunctional HCV-specific CD8+ T cells. As such, blockade of the PD-1/PD-L1 pathway in these CD8+ T cells might restore their functional capabilities. Indeed, clinical trials using therapies to block this pathway have shown promise in the fostering of anti-HCV immunity. Understanding how chronic HCV infection induces upregulation of PD-1 on HCV specific T cells and how the PD-1/PD-L1 interaction develops HCV specific T cell dysfunction will accelerate the development of an efficacious prophylactic and therapeutic vaccination against chronic HCV infections, which will significantly improve HCV treatments and patient survival. In this review, we discuss the relationship between PD-1 expression and clinical responses and the potential use of PD-1 blockade for anti-HCV therapy.
基金Supported by Higher Education Commission of Pakistanthrough Grant No.20-2056 to Iqbal M
文摘Hepatitis C virus(HCV) is endemic in Pakistan and its burden is expected to increase in coming decades owing mainly to widespread use of unsafe medical procedures. The prevalence of HCV in Pakistan has previously been reviewed. However, the literature search conducted here revealed that at least 86 relevant studies have been produced since the publication of these systematic reviews. A revised updated analysis was therefore needed in order to integrate the fresh data. A systematic review of data published between 2010 and 2015 showed that HCV seroprevalence among the general adult Pakistani population is 6.8%, while active HCV infection was found in approximately 6% of the population. Studies included in this review have also shown extremely high HCV prevalence in rural and underdeveloped peri-urban areas(up to 25%), highlighting the need for an increased focus on this previously neglected socioeconomic stratum of the population. While a 2.45% seroprevalence among blood donors demands immediate measures to curtail the risk of transfusion transmitted HCV, a very high prevalence in patients attending hospitals with various non-liver disease related complaints(up to 30%) suggests a rise in the incidence of nosocomial HCV spread. HCV genotype 3a continues to be the most prevalent subtype infecting people in Pakistan(61.3%). However, recent years have witnessed an increase in the frequency of subtype 2a in certain geographical sub-regions within Pakistan. In Khyber Pakhtunkhwa and Sindh provinces, 2a was the second most prevalent genotype(17.3% and 11.3% respectively). While the changing frequency distribution of various genotypes demands an increased emphasis on research for novel therapeutic regimens, evidence of high nosocomial transmission calls for immediate measures aimed at ensuring safe medical practices.
