The outbreak of the 2019-nCoV infection began in December 2019 in Wuhan,Hubei province,and rapidly spread to many provinces in China as well as other countries.Here we report the epidemiological,clinical,laboratory,an...The outbreak of the 2019-nCoV infection began in December 2019 in Wuhan,Hubei province,and rapidly spread to many provinces in China as well as other countries.Here we report the epidemiological,clinical,laboratory,and radiological characteristics,as well as potential biomarkers for predicting disease severity in 2019-nCoV-infected patients in Shenzhen,China.All 12 cases of the 2019-nCoV-infected patients developed pneumonia and half of them developed acute respiratory distress syndrome (ARDS).The most common laboratory abnormalities were hypoalbuminemia,lymphopenia,decreased percentage of lymphocytes (LYM) and neutrophils (NEU),elevated C-reactive protein (CRP) and lactate dehydrogenase (LDH),and decreased CD8 count.The viral load of 2019-nCoV detected from patient respiratory tracts was positively linked to lung disease severity.ALB,LYM,LYM (%),LDH,NEU (%),and CRP were highly correlated to the acute lung injury.Age,viral load,lung injury score,and blood biochemistry indexes,albumin (ALB),CRP,LDH,LYM (%),LYM,and NEU (%),may be predictors of disease severity.Moreover,the Angiotensin Ⅱlevel in the plasma sample from 2019-nCoV infected patients was markedly elevated and linearly associated to viral load and lung injury.Our results suggest a number of potential diagnosis biomarkers and angiotensin receptor blocker (ARB) drugs for potential repurposing treatment of 2019-nCoV infection.展开更多
Osteoarthritis （OA） is the most common degenerative joint disease and a major cause of pain and disability in adult individuals. The etiology of OA includes joint injury, obesity, aging, and heredity. However, the d...Osteoarthritis （OA） is the most common degenerative joint disease and a major cause of pain and disability in adult individuals. The etiology of OA includes joint injury, obesity, aging, and heredity. However, the detailed molecular mechanisms of OA initiation and progression remain poorly understood and, currently, there are no interventions available to restore degraded cartilage or decelerate disease progression. The diathrodial joint is a complicated organ and its function is to bear weight, perform physical activity and exhibit a joint-specific range of motion during movement. During OA development, the entire joint organ is affected, including articular cartilage, subchondral bone, synovial tissue and meniscus. A full understanding of the pathological mechanism of OA development relies on the discovery of the interplaying mechanisms among different OA symptoms, including articular cartilage degradation, osteophyte formation, subchondral sclerosis and synovial hyperplasia, and the signaling pathway（s） controlling these pathological processes.展开更多
Abiotic stresses and soil nutrient limitations are major environmental conditions that reduce plant growth,productivity and quality.Plants have evolved mechanisms to perceive these environmental challenges,transmit th...Abiotic stresses and soil nutrient limitations are major environmental conditions that reduce plant growth,productivity and quality.Plants have evolved mechanisms to perceive these environmental challenges,transmit the stress signals within cells as well as between cells and tissues,and make appropriate adjustments in their growth and development in order to survive and reproduce.In recent years,significant progress has been made on many fronts of the stress signaling research,particularly in understanding the downstream signaling events that culminate at the activation of stress-and nutrient limitation-responsive genes,cellular ion homeostasis,and growth adjustment.However,the revelation of the early events of stress signaling,particularly the identification of primary stress sensors,still lags behind.In this review,we summarize recent work on the genetic and molecular mechanisms of plant abiotic stress and nutrient limitation sensing and signaling and discuss new directions for future studies.展开更多
Carcinoma of the stomach is still the second most common cause of cancer death worldwide, although the incidence and mortality have fallen dramatically over the last 50 years in many regions. The incidence of gastric ...Carcinoma of the stomach is still the second most common cause of cancer death worldwide, although the incidence and mortality have fallen dramatically over the last 50 years in many regions. The incidence of gastric cancer varies in different parts of the world and among various ethnic groups. Despite advances in diagnosis and treatment, the 5-year survival rate of stomach cancer is only 20 per cent. Stomach cancer can be classified into intestinal and diffuse types based on epidemiological and clinicopathological features. The etiology of gastric cancer is multifactorial and includes both dietary and nondietary factors. The major diet-related risk factors implicated in stomach cancer development include high content of nitrates and high salt intake. Accumulating evidence has implicated the role of Helicobacter pylori (H. pylori) infection in the pathogenesis of gastric cancer. The development of gastric cancer is a complex, multistep process involving multiple genetic and epigenetic alterations of oncogenes, tumor suppressor genes, DNA repair genes, cell cycle regulators, and signaling molecules. A plausible program for gastric cancer prevention involves intake of a balanced diet containing fruits and vegetables, improved sanitationand hygiene, screening and treatment of H. pylori infection, and follow-up of precancerous lesions. The fact that diet plays an important role in the etiology of gastric cancer offers scope for nutritional chemoprevention. Animal models have been extensively used to analyze the stepwise evolution of gastric carcinogenesis and to test dietary chemopreventive agents. Development of multitargeted preventive and therapeutic strategies for gastric cancer is a major challenge for the future.展开更多
Atherosclerosis is a chronic inflammatory disease associated with cardiovascular dysfunction including myocardial infarction, unstable angina, sudden cardiac death, stroke and peripheral thromboses. It has been predic...Atherosclerosis is a chronic inflammatory disease associated with cardiovascular dysfunction including myocardial infarction, unstable angina, sudden cardiac death, stroke and peripheral thromboses. It has been predicted that atherosclerosis will be the primary cause of death in the world by 2020. Atherogenesis is initiated by endothelial injury due to oxidative stress associated with cardiovascular risk factors including diabetes mellitus, hypertension, cigarette smoking, dyslipidemia, obesity, and metabolic syndrome. The impairment of the endothelium associated with cardiovascular risk factors creates an imbalance between vasodilating and vasoconstricting factors, in particular, an increase in angiotensin Ⅱ(Ang Ⅱ) and a decrease in nitric oxide. The renin-angiotensin system(RAS), and its primary mediator Ang Ⅱ, also have a direct influence on the progression of the atherosclerotic process via effects on endothelial function, inflammation, fibrinolytic balance, and plaque stability. Anti-inflammatory agents [statins, secretory phospholipase A2 inhibitor, lipoprotein-associated phospholipase A2 inhibitor, 5-lipoxygenase activating protein, chemokine motif ligand-2, C-C chemokine motif receptor 2 pathway inhibitors, methotrexate, IL-1 pathway inhibitor and RAS inhibitors(angiotensin-converting enzyme inhibitors)], Ang Ⅱ receptor blockers and ranin inhibitors may slow inflammatory processes and disease progression. Several studies in human using anti-inflammatory agents and RAS inhibitors revealed vascular benefits and reduced progression of coronary atherosclerosis in patients with stable angina pectoris; decreased vascular inflammatory markers, improved common carotid intima-media thickness and plaque volume in patients with diagnosed atherosclerosis. Recent preclinical studies have demonstrated therapeutic efficacy of vitamin D analogs paricalcitol in Apo E-deficient atherosclerotic mice.展开更多
Dear Editor Salvia miltiorrhiza Bunge （Danshen） is a medicinal plant of the Lamiaceae family, and its dried roots have long been used in traditional Chinese medicine with hydrophilic phenolic acids and tanshinones a...Dear Editor Salvia miltiorrhiza Bunge （Danshen） is a medicinal plant of the Lamiaceae family, and its dried roots have long been used in traditional Chinese medicine with hydrophilic phenolic acids and tanshinones as pharmaceutically active components （Zhang et al., 2014; Xu et al., 2016）. The first step of tanshinone biosynthesis is bicyclization of the general diterpene precursor （E,E,E）-geranylgeranyl diphosphate （GGPP） to copalyl diphosphate （CPP） by CPP synthases （CPSs）, which is followed by a cyclization or rearrangement reaction catalyzed by kaurene synthase-like enzymes （KSL）. The resulting intermediate is usually an olefin, which requires the insertion of oxygen by cytochrome P450 mono-oxygenases （CYPs） for the final production of diterpenoids （Zi et al., 2014）. While the CPS, KSL, and several early acting CYPs （CYP76AH1, CYP76AH3, and CYP76AK1） for tanshinone biosynthesis have been identified in S. miltiorrhiza （Gao et al., 2009; Guo et al., 2013, 2016; Zi and Peters, 2013）, the majority of the overall biosynthetic pathway, as well as the relevant regulatory factors associated with tanshinone production, remains elusive （Figure 1B）.展开更多
Gallbladder cancer is a malignancy of biliary tract which is infrequent in developed countries but common in some specific geographical regions of developing countries. Late diagnosis and deprived prognosis are major ...Gallbladder cancer is a malignancy of biliary tract which is infrequent in developed countries but common in some specific geographical regions of developing countries. Late diagnosis and deprived prognosis are major problems for treatment of gallbladder carcinoma. The dramatic associations of this orphan cancer with various genetic and environmental factors are responsible for its poorly defined pathogenesis. An understanding to the relationship between epidemiology, molecular genetics and pathogenesis of gallbladder cancer can add new insights to its undetermined pathophysiology. Present review article provides a recent update regarding epidemiology, pathogenesis, and molecular genetics of gallbladder cancer. We systematically reviewed published literature on gallbladder cancer from online search engine Pub Med(http://www.ncbi.nlm.nih.gov/pubmed). Various keywords used for retrieval of articles were Gallbladder, cancer Epidemiology, molecular genetics and bullion operators like AND, OR, NOT. Cross references were manually searched from various online search engines(http://www.ncbi.nlm.nih.gov/pubmed,https://scholar.google.co.in/, http://www.medline.com/home.jsp). Most of the articles published from 1982 to 2015 in peer reviewed journals have been included in this review.展开更多
Human mesenchymal stem cells （hMSCs） can home to tumor sites and inhibit the growth of tumor cells. Little is known about the underlying molecular mechanisms that link hMSCs to the targeted inhibition of tumor cells...Human mesenchymal stem cells （hMSCs） can home to tumor sites and inhibit the growth of tumor cells. Little is known about the underlying molecular mechanisms that link hMSCs to the targeted inhibition of tumor cells. In this study, we investigated the effects of hMSCs on two human hepatoma cell lines （H7402 and HepG2） using an animal transplantation model, a co-culture system and conditioned media from hMSCs. Animal transplantation studies showed that the latent time for tumor formation was prolonged and that the tumor size was smaller when SCID mice were injected with H7402 cells and an equal number of Z3 hMSCs. When co-cultured with Z3 cells, H7402 cell proliferation decreased, apoptosis increased, and the expression of Bcl-2, c-Myc, proliferating cell nuclear antigen （PCNA） and survivin was downregulated. After treatment with conditioned media derived from Z3 hMSC cultures, H4702 cells showed decreased colony-forming ability and decreased proliferation. Immunoblot analysis showed that β-catenin, Bcl-2, c-Myc, PCNA and survivin expression was downregulated in H7402 and HepG2 cells. Taken together, our findings demonstrate that hMSCs inhibit the malignant phenotypes of the H7402 and HepG2 human liver cancer cell lines, which include proliferation, colony-forming ability and oncogene expression both in vitro and in vivo. Furthermore, our studies provide evidence that the Wnt signaling pathway may have a role in hMSC-mediated targeting and tumor cell inhibition.展开更多
Atherosclerosis is a chronic inflammatory vascular disease driven by traditional and nontraditional risk factors.Genome-wide association combined with clonal lineage tracing and clinical trials have demonstrated that ...Atherosclerosis is a chronic inflammatory vascular disease driven by traditional and nontraditional risk factors.Genome-wide association combined with clonal lineage tracing and clinical trials have demonstrated that innate and adaptive immune responses can promote or quell atherosclerosis.Several signaling pathways,that are associated with the inflammatory response,have been implicated within atherosclerosis such as NLRP3 inflammasome,toll-like receptors,proprotein convertase subtilisin/kexin type 9.展开更多
Background In steroid-induced osteonecrosis, hypertrophy and hyperplasia of marrow fat cells and lipid deposition of osteocytes can be found in the femoral head. However, the precise reason is not clear yet. The aim o...Background In steroid-induced osteonecrosis, hypertrophy and hyperplasia of marrow fat cells and lipid deposition of osteocytes can be found in the femoral head. However, the precise reason is not clear yet. The aim of this study was to observe the effect of dexamethasone （Dex） on differentiation of marrow stromal cells （MSCs）, and to investigate the pathobiological mechanism of steroid-induced osteonecrosis.Methods MSCs in cultures were treated with increasing concentrations of Dex （0, 10^-9, 10^-8, 10^-7, and 10^-6 mol/L） continuously for 21 days. The cells, which were exposed to 0 mol/L （control） or 10^-7 mol/L Dex for 4-21 days, were then cultured for 21 days without Dex. MSCs were stained with Sudan Ⅲ. Number of adipocytes was counted under a light microscope. The activity of alkaline phosphatase （ALP） of MSCs treated with 0, 10^-8, 10-7, and 10^-6 mol/L Dex for 12 days, and that treated with 0 mol/L and 10^-7 mol/L Dex for 8, 10, or 12 days were determined. The levels of triglycerides, osteocalcin and cell proliferation of MSCs treated with 0 mol/L and 10^-7 mol/L Dex were detected. The mRNA expression levels of adipose-specific 422（aP2） gene and osteogenic gene type I collagen in MSCs treated with 0 mol/L and 10^-7 mol/L Dex for 6 days were analyzed by whole-cell dot-blot hybridization. Statistical analysis was performed using Student＇s t test and analysis of variance. P values less than 0.05 were considered significant statistically.Results The number of adipocytes in cultures increased with the duration of MSCs＇ exposure to Dex and the concentration of Dex. The level of ALP activity in the MSCs decreased with concentration of Dex. In the control group, it was 8.69 times of that in the 10^-7 mol/L Dex group on day 12 （t=20.51, P〈0.001）. The level of triglycerides in 10^-7 mol/L Dex group was 3.40 times of that in the control （t=11.00, P〈0.001）. The levels of cell proliferation and osteocalcin in the control were 1.54 and 2.42 times of that in the 10^-7 mol/L Dex g展开更多
Inflammatory bowel diseases(IBD),including Crohn's disease and ulcerative colitis,are complex diseases that result from the chronic dysregulated immune response in the gastrointestinal tract. The exact etiology is...Inflammatory bowel diseases(IBD),including Crohn's disease and ulcerative colitis,are complex diseases that result from the chronic dysregulated immune response in the gastrointestinal tract. The exact etiology is not fully understood,but it is accepted that it occurs when an inappropriate aggressive inflammatory respon-se in a genetically susceptible host due to inciting environmental factors occurs. To investigate the path-ogenesis and etiology of human IBD,various animal models of IBD have been developed that provided indispensable insights into the histopathological and morphological changes as well as factors associated with the pathogenesis of IBD and evaluation of therapeutic options in the last few decades. The most widely used experimental model employs dextran sodium sulfate(DSS) to induce epithelial damage. The DSS colitis model in IBD research has advantages over other various chemically induced experimental models due to its rapidity,simplicity,reproducibility and controllability. In this manuscript,we review the newer publicized advances of research in murine colitis models that focus upon the disruption of the barrier function of the intestine,effects of mucin on the development of colitis,alterations found in microbial balance and resultant changes in the metabolome specifically in the DSS colitis murine model and its relation to the pathogenesis of IBD.展开更多
The epidemic nature of diabetes mellitus in different regions is reviewed. The Middle East and North Africa region has the highest prevalence of diabetes in adults(10.9%) whereas, the Western Pacific region has the hi...The epidemic nature of diabetes mellitus in different regions is reviewed. The Middle East and North Africa region has the highest prevalence of diabetes in adults(10.9%) whereas, the Western Pacific region has the highest number of adults diagnosed with diabetes and has countries with the highest prevalence of diabetes(37.5%). Different classes of diabetes mellitus, type 1, type 2, gestational diabetes and other types of diabetes mellitus are compared in terms of diagnostic criteria, etiology and genetics. The molecular genetics of diabetes received extensive attention in recent years by many prominent investigators and research groups in the biomedical field. A large array of mutations and single nucleotide polymorphisms in genes that play a role in the various steps and pathways involved in glucose metabolism and the development, control and function of pancreatic cells at various levels are reviewed. The major advances in the molecular understanding of diabetes in relation to the different types of diabetes in comparison to the previous understanding in this field are briefly reviewed here. Despite the accumulation of extensive data at the molecular and cellular levels, the mechanism of diabetes development and complications are still not fully understood. Definitely, more extensive research is needed in this field that will eventually reflect on the ultimate objective to improve diagnoses, therapy and minimize the chance of chronic complications development.展开更多
This review focuses on research findings in the area of diagnosis and pathogenesis of hepatitis C virus(HCV)infection over the last few decades.The information based on published literature provides an update on these...This review focuses on research findings in the area of diagnosis and pathogenesis of hepatitis C virus(HCV)infection over the last few decades.The information based on published literature provides an update on these two aspects of HCV.HCV infection,previously called blood transmitted non-A,non-B infection,is prevalent globally and poses a serious public health problem worldwide.The diagnosis of HCV infection has evolved from serodetection of non-specific and low avidity anti-HCV antibodies to detection of viral nucleic acid in serum using the polymerase chain reaction(PCR)technique.Current PCR assays detect viral nucleic acid with high accuracy and the exact copy number of viral particles.Moreover,multiplex assays using real-time PCR are available for identification of HCV-genotypes and their isotypes.In contrast to previous methods,the newly developed assays are not only fast and eco-nomic,but also resolve the problem of the window period as well as differentiate present from past infection.HCV is a non-cytopathic virus,thus,its pathogenesis is regulated by host immunity and metabolic changes including oxidative stress,insulin resistance and hepatic steatosis.Both innate and adaptive immunity play an important role in HCV pathogenesis.Cytotoxic lymphocytes demonstrate crucial activity during viral eradication or viral persistence and are influenced by viral proteins,HCV-quasispecies and several metabolic factors regulating liver metabolism.HCV pathogenesis is a very complex phenomenon and requires further study to determine the other factors involved.展开更多
Objective： To determine the clinical serum levels of carcinoembryonic antigen （CEA） and carbohydrate antigen 19-9 （CA19-9）, individually and in combination, for the diagnosis of 50 healthy subjects and 150 cases ...Objective： To determine the clinical serum levels of carcinoembryonic antigen （CEA） and carbohydrate antigen 19-9 （CA19-9）, individually and in combination, for the diagnosis of 50 healthy subjects and 150 cases of esophageal, gastric, and colon cancers. Methods： The sensitivities of the two markers were compared individually and in combination, with specificity set at 100%. Receiver operating characteristic （ROC） curves were plotted. Results： Serum CEA levels were significantly higher in cancer patients than in the control group. The sensitivity of CEA was determined： in esophageal cancer, sensitivity=28%, negative predictive value （NPV）=61.72%, and AUC=0.742 （SE=0.05）, with a significance level of P〈0.0001; in gastric cancer, sensitivity=30%, NPV=58.82%, and AUC=0.734 （SE=0.0S）, with a significance level of P〈0.0001; in colon cancer, sensitivity=74%, NPV=79.36%, and AUC=0.856 （SE=0.04）, with a significance level of P〈0.0001. The sensitivity of CA19-9 was also evaluated： in esophageal cancer, sensitivity=18%, NPV=54.94%, and AUC=0.573 （SE=0.05）, with a significance level of P=0.2054. In gastric cancer, sensitivity=42%, NPV=63.29%, and AUC=0.679 （SE=0.05）, with a significance level of P〈0.0011. In colon cancer, sensitivity=26%, NPV=57.47%, and AUC=0.S80 （SE=0.05）, with a significance level ofP=0.1670. The following were the sensitivities of CEA/CA19-9 combined： in esophageal cancer, sensitivity=42%, NPV=63.29%, SE=0.078 （95% CI： 0.0159-0.322）; gastric cancer, sensitivity=S8%, NPV=70.42%, SE=0.072 （9$% CI： -0.0866-0.198）; and colon cancer, sensitivity=72%, NPV=78.12%, SE=0.070 （9S% CI： 0.137-0.415）. Conclusion： CEA exhibited the highest sensitivity for colon cancer, and CA19-9 exhibited the highest sensitivity for gastric cancer. Combined analysis indicated an increase in diagnostic sensitivity in esophageal and gastric cancer compared with that in colon cancer.展开更多
Osteoarthritis(OA)is a chronic degenerative joint disorder that leads to disability and affects more than 500 million population worldwide.OA was believed to be caused by the wearing and tearing of articular cartilage...Osteoarthritis(OA)is a chronic degenerative joint disorder that leads to disability and affects more than 500 million population worldwide.OA was believed to be caused by the wearing and tearing of articular cartilage,but it is now more commonly referred to as a chronic whole-joint disorder that is initiated with biochemical and cellular alterations in the synovial joint tissues,which leads to the histological and structural changes of the joint and ends up with the whole tissue dysfunction.Currently,there is no cure for OA,partly due to a lack of comprehensive understanding of the pathological mechanism of the initiation and progression of the disease.Therefore,a better understanding of pathological signaling pathways and key molecules involved in OA pathogenesis is crucial for therapeutic target design and drug development.In this review,we first summarize the epidemiology of OA,including its prevalence,incidence and burdens,and OA risk factors.We then focus on the roles and regulation of the pathological signaling pathways,such as Wnt/β-catenin,NF-κB,focal adhesion,HIFs,TGFβ/ΒΜP and FGF signaling pathways,and key regulators AMPK,mTOR,and RUNX2 in the onset and development of OA.In addition,the roles of factors associated with OA,including MMPs,ADAMTS/ADAMs,and PRG4,are discussed in detail.Finally,we provide updates on the current clinical therapies and clinical trials of biological treatments and drugs for OA.Research advances in basic knowledge of articular cartilage biology and OA pathogenesis will have a significant impact and translational value in developing OA therapeutic strategies.展开更多
Hepatocellular carcinoma(HCC), the predominant type of primary liver cancer, is one of the most serious lifethreatening malignancies, worldwide. In majority of the cases, HCC develops after prolonged and persistent ch...Hepatocellular carcinoma(HCC), the predominant type of primary liver cancer, is one of the most serious lifethreatening malignancies, worldwide. In majority of the cases, HCC develops after prolonged and persistent chronic liver disease. hepatitis B virus(HBV) or HCV infection is prominent etiological factors, attributing to this condition. It has been well documented that HBV, being the inducer of chronic inflammation, is the main causative agent in causing HCC, particularly in Asian countries. The HBV infection leads to a wide range of clinical symptoms from carrier state to malignancy. Cytokines being immune-modulatory molecules, are the key mediators in the defense mechanism against viral infection. In this regard, this review will detail the substantial role of key Th1: interleukin 1(IL-1), IL-2, IL-12, tumor necrosis factor-α, interferon-γ; Th2: IL-4, IL-10 and non Th1/Th2: IL-6, transforming growth factor-β1 cytokines genotypes in analyzing the variability in the clinical manifestations in an HBV-afflicted individual, which might finally, culminates into HCC. Since cytokine production is regulated genetically, the cytokine promoter region single-nucleotide polymorphisms induced changes, greatly affects the cytokine production, thus resulting into differential outcome of immune balance.展开更多
DNA mismatch repair （MMR） is a highly conserved biological pathway that plays a key role in maintaining genomic stability. The specificity of MMR is primarily for base-base mismatches and insertion/deletion mispairs...DNA mismatch repair （MMR） is a highly conserved biological pathway that plays a key role in maintaining genomic stability. The specificity of MMR is primarily for base-base mismatches and insertion/deletion mispairs generated during DNA replication and recombination. MMR also suppresses homeologous recombination and was recently shown to play a role in DNA damage signaling in eukaryotic cells. Escherichia coli MutS and MutL and their eukaryotic homologs, MutSα and MutLα, respectively, are key players in MMR-associated genome maintenance. Many other protein components that participate in various DNA metabolic pathways, such as PCNA and RPA, are also essential for MMR. Defects in MMR are associated with genome-wide instability, predisposition to certain types of cancer including hereditary non-polyposis colorectal cancer, resistance to certain chemotherapeutic agents, and abnormalities in meiosis and sterility in mammalian systems.展开更多
Human intestinal microbiota create a complex polymi-crobial ecology. This is characterised by its high population density, wide diversity and complexity of interaction. Any dysbalance of this complex intestinal microb...Human intestinal microbiota create a complex polymi-crobial ecology. This is characterised by its high population density, wide diversity and complexity of interaction. Any dysbalance of this complex intestinal microbiome, both qualitative and quantitative, might have serious health consequence for a macro-organism, including small intestinal bacterial overgrowth syndrome (SIBO).SIBO is defined as an increase in the number and/or alteration in the type of bacteria in the upper gastro-intestinal tract. There are several endogenous defence mechanisms for preventing bacterial overgrowth: gastric acid secretion, intestinal motility, intact ileo-caecal valve, immunoglobulins within intestinal secretion and bacte-riostatic properties of pancreatic and biliary secretion. Aetiology of SIBO is usually complex, associated with disorders of protective antibacterial mechanisms (e.g. achlorhydria, pancreatic exocrine insuff iciency, immuno-deficiency syndromes), anatomical abnormalities (e.g. small intestinal obstruction, diverticula, f istulae, surgical blind loop, previous ileo-caecal resections) and/or motility disorders (e.g. scleroderma, autonomic neuropathy in diabetes mellitus, post-radiation enteropathy, small intestinal pseudo-obstruction). In some patients more than one factor may be involved. Symptoms related to SIBO are bloating, diarrhoea, malabsorption, weight loss and malnutrition. The gold standard for diagnosing SIBO is still microbial investigation of jejunal aspirates. Noninvasive hydrogen and methane breath tests are most commonly used for the diagnosis of SIBO using glucose or lactulose. Therapy for SIBO must be com-plex, addressing all causes, symptoms and complica-tions, and fully individualised. It should include treatment of the underlying disease, nutritional support and cyclical gastro-intestinal selective antibiotics. Prognosis is usually serious, determined mostly by the underlying disease that led to SIBO.展开更多
Growth-defense tradeoffs are thought to occur in plants due to resource restrictions, which demand prior- itization towards either growth or defense, depending on external and internal factors. These tradeoffs have pr...Growth-defense tradeoffs are thought to occur in plants due to resource restrictions, which demand prior- itization towards either growth or defense, depending on external and internal factors. These tradeoffs have profound implications in agriculture and natural ecosystems, as both processes are vital for plant survival, reproduction, and, ulti- mately, plant fitness. While many of the molecular mechanisms underlying growth and defense tradeoffs remain to be elucidated, hormone crosstalk has emerged as a major player in regulating tradeoffs needed to achieve a balance. In this review, we cover recent advances in understanding growth-defense tradeoffs in plants as well as what is known regard- ing the underlying molecular mechanisms. Specifically, we address evidence supporting the growth-defense tradeoff concept, as well as known interactions between defense signaling and growth signaling. Understanding the molecular basis of these tradeoffs in plants should provide a foundation for the development of breeding strategies that optimize the growth-defense balance to maximize crop yield to meet rising global food and biofuel demands.展开更多
Objective:Our previous research showed that Naotaifang(a compound traditional Chinese herbal medicine)extract(NTE)has clinically beneficial effects on neurological improvement of patients with acute cerebral ischemia....Objective:Our previous research showed that Naotaifang(a compound traditional Chinese herbal medicine)extract(NTE)has clinically beneficial effects on neurological improvement of patients with acute cerebral ischemia.In this study,we investigated whether NTE protected acute brain injury in rats and whether its effects on ferroptosis could be linked to the dysfunction of glutathione peroxidase 4(GPX4)and iron metabolism.Methods:We established an acute brain injury model of middle cerebral artery occlusion(MCAO)in rats,in which we could observe the accumulation of iron in neurons,as detected by Perl’s staining.Using assay kits,we measured expression levels of ferroptosis biomarkers,such as iron,glutathione(GSH),reactive oxygen species(ROS)and malonaldehyde(MDA);further the expression levels of transferrin receptor1(TFR1),divalent metal transporter 1(DMT1),solute carrier family 7 member 11(SLC7 A11)and GPX4 were determined using immunohistochemical analysis,real-time quantitative polymerase chain reaction and Western blot assays.Results:We found that treatment with NTE reduced the expression levels of TFR1 and DMT1,reduced ROS,MDA and iron accumulation and reduced neurobehavioral scores,relative to untreated MCAO rats.Treatment with NTE increased the expression levels of SLC7 A11,GPX4 and GSH,and the number of Nissl bodies in the MCAO rats.Conclusion:Taken together,our data suggest that acute cerebral ischemia induces neuronal ferroptosis and the effects of treating MCAO rats with NTE involved inhibition of ferroptosis through the TFR1/DMT1 and SCL7 A11/GPX4 pathways.展开更多
基金This work was supported by the National Science and Technology Major Project(2017ZX10103011 and 2017ZX10204401)Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences(2017-I2M-1-009)+1 种基金Shenzhen Science and Technology Research and Development Project(JCYJ20180504165549581 and JCYJ20170413141236903)China Postdoctoral Science Foundation(2019T120147).
文摘The outbreak of the 2019-nCoV infection began in December 2019 in Wuhan,Hubei province,and rapidly spread to many provinces in China as well as other countries.Here we report the epidemiological,clinical,laboratory,and radiological characteristics,as well as potential biomarkers for predicting disease severity in 2019-nCoV-infected patients in Shenzhen,China.All 12 cases of the 2019-nCoV-infected patients developed pneumonia and half of them developed acute respiratory distress syndrome (ARDS).The most common laboratory abnormalities were hypoalbuminemia,lymphopenia,decreased percentage of lymphocytes (LYM) and neutrophils (NEU),elevated C-reactive protein (CRP) and lactate dehydrogenase (LDH),and decreased CD8 count.The viral load of 2019-nCoV detected from patient respiratory tracts was positively linked to lung disease severity.ALB,LYM,LYM (%),LDH,NEU (%),and CRP were highly correlated to the acute lung injury.Age,viral load,lung injury score,and blood biochemistry indexes,albumin (ALB),CRP,LDH,LYM (%),LYM,and NEU (%),may be predictors of disease severity.Moreover,the Angiotensin Ⅱlevel in the plasma sample from 2019-nCoV infected patients was markedly elevated and linearly associated to viral load and lung injury.Our results suggest a number of potential diagnosis biomarkers and angiotensin receptor blocker (ARB) drugs for potential repurposing treatment of 2019-nCoV infection.
基金supported by NIH grants AR055915 and AR054465 to DC
文摘Osteoarthritis （OA） is the most common degenerative joint disease and a major cause of pain and disability in adult individuals. The etiology of OA includes joint injury, obesity, aging, and heredity. However, the detailed molecular mechanisms of OA initiation and progression remain poorly understood and, currently, there are no interventions available to restore degraded cartilage or decelerate disease progression. The diathrodial joint is a complicated organ and its function is to bear weight, perform physical activity and exhibit a joint-specific range of motion during movement. During OA development, the entire joint organ is affected, including articular cartilage, subchondral bone, synovial tissue and meniscus. A full understanding of the pathological mechanism of OA development relies on the discovery of the interplaying mechanisms among different OA symptoms, including articular cartilage degradation, osteophyte formation, subchondral sclerosis and synovial hyperplasia, and the signaling pathway（s） controlling these pathological processes.
文摘Abiotic stresses and soil nutrient limitations are major environmental conditions that reduce plant growth,productivity and quality.Plants have evolved mechanisms to perceive these environmental challenges,transmit the stress signals within cells as well as between cells and tissues,and make appropriate adjustments in their growth and development in order to survive and reproduce.In recent years,significant progress has been made on many fronts of the stress signaling research,particularly in understanding the downstream signaling events that culminate at the activation of stress-and nutrient limitation-responsive genes,cellular ion homeostasis,and growth adjustment.However,the revelation of the early events of stress signaling,particularly the identification of primary stress sensors,still lags behind.In this review,we summarize recent work on the genetic and molecular mechanisms of plant abiotic stress and nutrient limitation sensing and signaling and discuss new directions for future studies.
基金Supported by A Grant from the Department of Biotechnology,New Delhi, India under the 7th FP of the Indo-EU Joint Collaborative Project on "FUNCFOOD"
文摘Carcinoma of the stomach is still the second most common cause of cancer death worldwide, although the incidence and mortality have fallen dramatically over the last 50 years in many regions. The incidence of gastric cancer varies in different parts of the world and among various ethnic groups. Despite advances in diagnosis and treatment, the 5-year survival rate of stomach cancer is only 20 per cent. Stomach cancer can be classified into intestinal and diffuse types based on epidemiological and clinicopathological features. The etiology of gastric cancer is multifactorial and includes both dietary and nondietary factors. The major diet-related risk factors implicated in stomach cancer development include high content of nitrates and high salt intake. Accumulating evidence has implicated the role of Helicobacter pylori (H. pylori) infection in the pathogenesis of gastric cancer. The development of gastric cancer is a complex, multistep process involving multiple genetic and epigenetic alterations of oncogenes, tumor suppressor genes, DNA repair genes, cell cycle regulators, and signaling molecules. A plausible program for gastric cancer prevention involves intake of a balanced diet containing fruits and vegetables, improved sanitationand hygiene, screening and treatment of H. pylori infection, and follow-up of precancerous lesions. The fact that diet plays an important role in the etiology of gastric cancer offers scope for nutritional chemoprevention. Animal models have been extensively used to analyze the stepwise evolution of gastric carcinogenesis and to test dietary chemopreventive agents. Development of multitargeted preventive and therapeutic strategies for gastric cancer is a major challenge for the future.
文摘Atherosclerosis is a chronic inflammatory disease associated with cardiovascular dysfunction including myocardial infarction, unstable angina, sudden cardiac death, stroke and peripheral thromboses. It has been predicted that atherosclerosis will be the primary cause of death in the world by 2020. Atherogenesis is initiated by endothelial injury due to oxidative stress associated with cardiovascular risk factors including diabetes mellitus, hypertension, cigarette smoking, dyslipidemia, obesity, and metabolic syndrome. The impairment of the endothelium associated with cardiovascular risk factors creates an imbalance between vasodilating and vasoconstricting factors, in particular, an increase in angiotensin Ⅱ(Ang Ⅱ) and a decrease in nitric oxide. The renin-angiotensin system(RAS), and its primary mediator Ang Ⅱ, also have a direct influence on the progression of the atherosclerotic process via effects on endothelial function, inflammation, fibrinolytic balance, and plaque stability. Anti-inflammatory agents [statins, secretory phospholipase A2 inhibitor, lipoprotein-associated phospholipase A2 inhibitor, 5-lipoxygenase activating protein, chemokine motif ligand-2, C-C chemokine motif receptor 2 pathway inhibitors, methotrexate, IL-1 pathway inhibitor and RAS inhibitors(angiotensin-converting enzyme inhibitors)], Ang Ⅱ receptor blockers and ranin inhibitors may slow inflammatory processes and disease progression. Several studies in human using anti-inflammatory agents and RAS inhibitors revealed vascular benefits and reduced progression of coronary atherosclerosis in patients with stable angina pectoris; decreased vascular inflammatory markers, improved common carotid intima-media thickness and plaque volume in patients with diagnosed atherosclerosis. Recent preclinical studies have demonstrated therapeutic efficacy of vitamin D analogs paricalcitol in Apo E-deficient atherosclerotic mice.
文摘Dear Editor Salvia miltiorrhiza Bunge （Danshen） is a medicinal plant of the Lamiaceae family, and its dried roots have long been used in traditional Chinese medicine with hydrophilic phenolic acids and tanshinones as pharmaceutically active components （Zhang et al., 2014; Xu et al., 2016）. The first step of tanshinone biosynthesis is bicyclization of the general diterpene precursor （E,E,E）-geranylgeranyl diphosphate （GGPP） to copalyl diphosphate （CPP） by CPP synthases （CPSs）, which is followed by a cyclization or rearrangement reaction catalyzed by kaurene synthase-like enzymes （KSL）. The resulting intermediate is usually an olefin, which requires the insertion of oxygen by cytochrome P450 mono-oxygenases （CYPs） for the final production of diterpenoids （Zi et al., 2014）. While the CPS, KSL, and several early acting CYPs （CYP76AH1, CYP76AH3, and CYP76AK1） for tanshinone biosynthesis have been identified in S. miltiorrhiza （Gao et al., 2009; Guo et al., 2013, 2016; Zi and Peters, 2013）, the majority of the overall biosynthetic pathway, as well as the relevant regulatory factors associated with tanshinone production, remains elusive （Figure 1B）.
文摘Gallbladder cancer is a malignancy of biliary tract which is infrequent in developed countries but common in some specific geographical regions of developing countries. Late diagnosis and deprived prognosis are major problems for treatment of gallbladder carcinoma. The dramatic associations of this orphan cancer with various genetic and environmental factors are responsible for its poorly defined pathogenesis. An understanding to the relationship between epidemiology, molecular genetics and pathogenesis of gallbladder cancer can add new insights to its undetermined pathophysiology. Present review article provides a recent update regarding epidemiology, pathogenesis, and molecular genetics of gallbladder cancer. We systematically reviewed published literature on gallbladder cancer from online search engine Pub Med(http://www.ncbi.nlm.nih.gov/pubmed). Various keywords used for retrieval of articles were Gallbladder, cancer Epidemiology, molecular genetics and bullion operators like AND, OR, NOT. Cross references were manually searched from various online search engines(http://www.ncbi.nlm.nih.gov/pubmed,https://scholar.google.co.in/, http://www.medline.com/home.jsp). Most of the articles published from 1982 to 2015 in peer reviewed journals have been included in this review.
基金This work was supported by grants from the National Basic Research Program of China （973 Program, No. 2007CB914800 to Xiaodong Zhang）, National Natural Science Foundation of China （No. 30570698 to Xiaodong Zhang） and Tianjin Natural Scientific Foundation （No. 033801211 to Xiaodong Zhang）.
文摘Human mesenchymal stem cells （hMSCs） can home to tumor sites and inhibit the growth of tumor cells. Little is known about the underlying molecular mechanisms that link hMSCs to the targeted inhibition of tumor cells. In this study, we investigated the effects of hMSCs on two human hepatoma cell lines （H7402 and HepG2） using an animal transplantation model, a co-culture system and conditioned media from hMSCs. Animal transplantation studies showed that the latent time for tumor formation was prolonged and that the tumor size was smaller when SCID mice were injected with H7402 cells and an equal number of Z3 hMSCs. When co-cultured with Z3 cells, H7402 cell proliferation decreased, apoptosis increased, and the expression of Bcl-2, c-Myc, proliferating cell nuclear antigen （PCNA） and survivin was downregulated. After treatment with conditioned media derived from Z3 hMSC cultures, H4702 cells showed decreased colony-forming ability and decreased proliferation. Immunoblot analysis showed that β-catenin, Bcl-2, c-Myc, PCNA and survivin expression was downregulated in H7402 and HepG2 cells. Taken together, our findings demonstrate that hMSCs inhibit the malignant phenotypes of the H7402 and HepG2 human liver cancer cell lines, which include proliferation, colony-forming ability and oncogene expression both in vitro and in vivo. Furthermore, our studies provide evidence that the Wnt signaling pathway may have a role in hMSC-mediated targeting and tumor cell inhibition.
基金This work was supported by the National Natural Science Foundation of China(91739301,91849102)the Key Natural Science Foundation Projects of Hebei Province(H2019206028)+1 种基金Natural Science Foundation of Hebei Province(H2021206006)Natural Science Youth Fund of Hebei Province Education Department(QN2020167).
文摘Atherosclerosis is a chronic inflammatory vascular disease driven by traditional and nontraditional risk factors.Genome-wide association combined with clonal lineage tracing and clinical trials have demonstrated that innate and adaptive immune responses can promote or quell atherosclerosis.Several signaling pathways,that are associated with the inflammatory response,have been implicated within atherosclerosis such as NLRP3 inflammasome,toll-like receptors,proprotein convertase subtilisin/kexin type 9.
文摘Background In steroid-induced osteonecrosis, hypertrophy and hyperplasia of marrow fat cells and lipid deposition of osteocytes can be found in the femoral head. However, the precise reason is not clear yet. The aim of this study was to observe the effect of dexamethasone （Dex） on differentiation of marrow stromal cells （MSCs）, and to investigate the pathobiological mechanism of steroid-induced osteonecrosis.Methods MSCs in cultures were treated with increasing concentrations of Dex （0, 10^-9, 10^-8, 10^-7, and 10^-6 mol/L） continuously for 21 days. The cells, which were exposed to 0 mol/L （control） or 10^-7 mol/L Dex for 4-21 days, were then cultured for 21 days without Dex. MSCs were stained with Sudan Ⅲ. Number of adipocytes was counted under a light microscope. The activity of alkaline phosphatase （ALP） of MSCs treated with 0, 10^-8, 10-7, and 10^-6 mol/L Dex for 12 days, and that treated with 0 mol/L and 10^-7 mol/L Dex for 8, 10, or 12 days were determined. The levels of triglycerides, osteocalcin and cell proliferation of MSCs treated with 0 mol/L and 10^-7 mol/L Dex were detected. The mRNA expression levels of adipose-specific 422（aP2） gene and osteogenic gene type I collagen in MSCs treated with 0 mol/L and 10^-7 mol/L Dex for 6 days were analyzed by whole-cell dot-blot hybridization. Statistical analysis was performed using Student＇s t test and analysis of variance. P values less than 0.05 were considered significant statistically.Results The number of adipocytes in cultures increased with the duration of MSCs＇ exposure to Dex and the concentration of Dex. The level of ALP activity in the MSCs decreased with concentration of Dex. In the control group, it was 8.69 times of that in the 10^-7 mol/L Dex group on day 12 （t=20.51, P〈0.001）. The level of triglycerides in 10^-7 mol/L Dex group was 3.40 times of that in the control （t=11.00, P〈0.001）. The levels of cell proliferation and osteocalcin in the control were 1.54 and 2.42 times of that in the 10^-7 mol/L Dex g
基金Supported by the Department of Veterans Affairs,Office of Research and Development(Biomedical Laboratory Research and Development)No.BX001155
文摘Inflammatory bowel diseases(IBD),including Crohn's disease and ulcerative colitis,are complex diseases that result from the chronic dysregulated immune response in the gastrointestinal tract. The exact etiology is not fully understood,but it is accepted that it occurs when an inappropriate aggressive inflammatory respon-se in a genetically susceptible host due to inciting environmental factors occurs. To investigate the path-ogenesis and etiology of human IBD,various animal models of IBD have been developed that provided indispensable insights into the histopathological and morphological changes as well as factors associated with the pathogenesis of IBD and evaluation of therapeutic options in the last few decades. The most widely used experimental model employs dextran sodium sulfate(DSS) to induce epithelial damage. The DSS colitis model in IBD research has advantages over other various chemically induced experimental models due to its rapidity,simplicity,reproducibility and controllability. In this manuscript,we review the newer publicized advances of research in murine colitis models that focus upon the disruption of the barrier function of the intestine,effects of mucin on the development of colitis,alterations found in microbial balance and resultant changes in the metabolome specifically in the DSS colitis murine model and its relation to the pathogenesis of IBD.
文摘The epidemic nature of diabetes mellitus in different regions is reviewed. The Middle East and North Africa region has the highest prevalence of diabetes in adults(10.9%) whereas, the Western Pacific region has the highest number of adults diagnosed with diabetes and has countries with the highest prevalence of diabetes(37.5%). Different classes of diabetes mellitus, type 1, type 2, gestational diabetes and other types of diabetes mellitus are compared in terms of diagnostic criteria, etiology and genetics. The molecular genetics of diabetes received extensive attention in recent years by many prominent investigators and research groups in the biomedical field. A large array of mutations and single nucleotide polymorphisms in genes that play a role in the various steps and pathways involved in glucose metabolism and the development, control and function of pancreatic cells at various levels are reviewed. The major advances in the molecular understanding of diabetes in relation to the different types of diabetes in comparison to the previous understanding in this field are briefly reviewed here. Despite the accumulation of extensive data at the molecular and cellular levels, the mechanism of diabetes development and complications are still not fully understood. Definitely, more extensive research is needed in this field that will eventually reflect on the ultimate objective to improve diagnoses, therapy and minimize the chance of chronic complications development.
文摘This review focuses on research findings in the area of diagnosis and pathogenesis of hepatitis C virus(HCV)infection over the last few decades.The information based on published literature provides an update on these two aspects of HCV.HCV infection,previously called blood transmitted non-A,non-B infection,is prevalent globally and poses a serious public health problem worldwide.The diagnosis of HCV infection has evolved from serodetection of non-specific and low avidity anti-HCV antibodies to detection of viral nucleic acid in serum using the polymerase chain reaction(PCR)technique.Current PCR assays detect viral nucleic acid with high accuracy and the exact copy number of viral particles.Moreover,multiplex assays using real-time PCR are available for identification of HCV-genotypes and their isotypes.In contrast to previous methods,the newly developed assays are not only fast and eco-nomic,but also resolve the problem of the window period as well as differentiate present from past infection.HCV is a non-cytopathic virus,thus,its pathogenesis is regulated by host immunity and metabolic changes including oxidative stress,insulin resistance and hepatic steatosis.Both innate and adaptive immunity play an important role in HCV pathogenesis.Cytotoxic lymphocytes demonstrate crucial activity during viral eradication or viral persistence and are influenced by viral proteins,HCV-quasispecies and several metabolic factors regulating liver metabolism.HCV pathogenesis is a very complex phenomenon and requires further study to determine the other factors involved.
基金the financial support provided by the Biotechnology Information Service–Sub-Distributed Information Centre(supported by the Department of Biotechnology,Government of India)Advanced Bioinformatics Centre(supported by the Government of Rajasthan)at Birla Institute of Scientific Research for the infrastructure and facilities for conducting statistical work
文摘Objective： To determine the clinical serum levels of carcinoembryonic antigen （CEA） and carbohydrate antigen 19-9 （CA19-9）, individually and in combination, for the diagnosis of 50 healthy subjects and 150 cases of esophageal, gastric, and colon cancers. Methods： The sensitivities of the two markers were compared individually and in combination, with specificity set at 100%. Receiver operating characteristic （ROC） curves were plotted. Results： Serum CEA levels were significantly higher in cancer patients than in the control group. The sensitivity of CEA was determined： in esophageal cancer, sensitivity=28%, negative predictive value （NPV）=61.72%, and AUC=0.742 （SE=0.05）, with a significance level of P〈0.0001; in gastric cancer, sensitivity=30%, NPV=58.82%, and AUC=0.734 （SE=0.0S）, with a significance level of P〈0.0001; in colon cancer, sensitivity=74%, NPV=79.36%, and AUC=0.856 （SE=0.04）, with a significance level of P〈0.0001. The sensitivity of CA19-9 was also evaluated： in esophageal cancer, sensitivity=18%, NPV=54.94%, and AUC=0.573 （SE=0.05）, with a significance level of P=0.2054. In gastric cancer, sensitivity=42%, NPV=63.29%, and AUC=0.679 （SE=0.05）, with a significance level of P〈0.0011. In colon cancer, sensitivity=26%, NPV=57.47%, and AUC=0.S80 （SE=0.05）, with a significance level ofP=0.1670. The following were the sensitivities of CEA/CA19-9 combined： in esophageal cancer, sensitivity=42%, NPV=63.29%, SE=0.078 （95% CI： 0.0159-0.322）; gastric cancer, sensitivity=S8%, NPV=70.42%, SE=0.072 （9$% CI： -0.0866-0.198）; and colon cancer, sensitivity=72%, NPV=78.12%, SE=0.070 （9S% CI： 0.137-0.415）. Conclusion： CEA exhibited the highest sensitivity for colon cancer, and CA19-9 exhibited the highest sensitivity for gastric cancer. Combined analysis indicated an increase in diagnostic sensitivity in esophageal and gastric cancer compared with that in colon cancer.
基金We apologize to the authors whose relevant studies have not been included in this review article. This work was supported, in part, by the National Key Research and Development Program of China Grants (2019YFA0906004)the National Natural Science Foundation of China Grants (82230081, 82250710175, 82172375, 81991513, and 82261160395)+3 种基金the Shenzhen Stable Support Plan Program for Higher Education Institutions (20200925150409001)the Shenzhen Fundamental Research Program (JCYJ20220818100617036)the Shenzhen Key Laboratory of Cell Microenvironment Grant (ZDSYS20140509142721429)the Guangdong Provincial Science and Technology Innovation Council Grant (2017B030301018).
文摘Osteoarthritis(OA)is a chronic degenerative joint disorder that leads to disability and affects more than 500 million population worldwide.OA was believed to be caused by the wearing and tearing of articular cartilage,but it is now more commonly referred to as a chronic whole-joint disorder that is initiated with biochemical and cellular alterations in the synovial joint tissues,which leads to the histological and structural changes of the joint and ends up with the whole tissue dysfunction.Currently,there is no cure for OA,partly due to a lack of comprehensive understanding of the pathological mechanism of the initiation and progression of the disease.Therefore,a better understanding of pathological signaling pathways and key molecules involved in OA pathogenesis is crucial for therapeutic target design and drug development.In this review,we first summarize the epidemiology of OA,including its prevalence,incidence and burdens,and OA risk factors.We then focus on the roles and regulation of the pathological signaling pathways,such as Wnt/β-catenin,NF-κB,focal adhesion,HIFs,TGFβ/ΒΜP and FGF signaling pathways,and key regulators AMPK,mTOR,and RUNX2 in the onset and development of OA.In addition,the roles of factors associated with OA,including MMPs,ADAMTS/ADAMs,and PRG4,are discussed in detail.Finally,we provide updates on the current clinical therapies and clinical trials of biological treatments and drugs for OA.Research advances in basic knowledge of articular cartilage biology and OA pathogenesis will have a significant impact and translational value in developing OA therapeutic strategies.
文摘Hepatocellular carcinoma(HCC), the predominant type of primary liver cancer, is one of the most serious lifethreatening malignancies, worldwide. In majority of the cases, HCC develops after prolonged and persistent chronic liver disease. hepatitis B virus(HBV) or HCV infection is prominent etiological factors, attributing to this condition. It has been well documented that HBV, being the inducer of chronic inflammation, is the main causative agent in causing HCC, particularly in Asian countries. The HBV infection leads to a wide range of clinical symptoms from carrier state to malignancy. Cytokines being immune-modulatory molecules, are the key mediators in the defense mechanism against viral infection. In this regard, this review will detail the substantial role of key Th1: interleukin 1(IL-1), IL-2, IL-12, tumor necrosis factor-α, interferon-γ; Th2: IL-4, IL-10 and non Th1/Th2: IL-6, transforming growth factor-β1 cytokines genotypes in analyzing the variability in the clinical manifestations in an HBV-afflicted individual, which might finally, culminates into HCC. Since cytokine production is regulated genetically, the cytokine promoter region single-nucleotide polymorphisms induced changes, greatly affects the cytokine production, thus resulting into differential outcome of immune balance.
文摘DNA mismatch repair （MMR） is a highly conserved biological pathway that plays a key role in maintaining genomic stability. The specificity of MMR is primarily for base-base mismatches and insertion/deletion mispairs generated during DNA replication and recombination. MMR also suppresses homeologous recombination and was recently shown to play a role in DNA damage signaling in eukaryotic cells. Escherichia coli MutS and MutL and their eukaryotic homologs, MutSα and MutLα, respectively, are key players in MMR-associated genome maintenance. Many other protein components that participate in various DNA metabolic pathways, such as PCNA and RPA, are also essential for MMR. Defects in MMR are associated with genome-wide instability, predisposition to certain types of cancer including hereditary non-polyposis colorectal cancer, resistance to certain chemotherapeutic agents, and abnormalities in meiosis and sterility in mammalian systems.
基金Supported by The Research Project MZO 00179906 from the Ministry of Health, Czech Republicby Research Grant GACR 305/08/0535, Czech Republic
文摘Human intestinal microbiota create a complex polymi-crobial ecology. This is characterised by its high population density, wide diversity and complexity of interaction. Any dysbalance of this complex intestinal microbiome, both qualitative and quantitative, might have serious health consequence for a macro-organism, including small intestinal bacterial overgrowth syndrome (SIBO).SIBO is defined as an increase in the number and/or alteration in the type of bacteria in the upper gastro-intestinal tract. There are several endogenous defence mechanisms for preventing bacterial overgrowth: gastric acid secretion, intestinal motility, intact ileo-caecal valve, immunoglobulins within intestinal secretion and bacte-riostatic properties of pancreatic and biliary secretion. Aetiology of SIBO is usually complex, associated with disorders of protective antibacterial mechanisms (e.g. achlorhydria, pancreatic exocrine insuff iciency, immuno-deficiency syndromes), anatomical abnormalities (e.g. small intestinal obstruction, diverticula, f istulae, surgical blind loop, previous ileo-caecal resections) and/or motility disorders (e.g. scleroderma, autonomic neuropathy in diabetes mellitus, post-radiation enteropathy, small intestinal pseudo-obstruction). In some patients more than one factor may be involved. Symptoms related to SIBO are bloating, diarrhoea, malabsorption, weight loss and malnutrition. The gold standard for diagnosing SIBO is still microbial investigation of jejunal aspirates. Noninvasive hydrogen and methane breath tests are most commonly used for the diagnosis of SIBO using glucose or lactulose. Therapy for SIBO must be com-plex, addressing all causes, symptoms and complica-tions, and fully individualised. It should include treatment of the underlying disease, nutritional support and cyclical gastro-intestinal selective antibiotics. Prognosis is usually serious, determined mostly by the underlying disease that led to SIBO.
文摘Growth-defense tradeoffs are thought to occur in plants due to resource restrictions, which demand prior- itization towards either growth or defense, depending on external and internal factors. These tradeoffs have profound implications in agriculture and natural ecosystems, as both processes are vital for plant survival, reproduction, and, ulti- mately, plant fitness. While many of the molecular mechanisms underlying growth and defense tradeoffs remain to be elucidated, hormone crosstalk has emerged as a major player in regulating tradeoffs needed to achieve a balance. In this review, we cover recent advances in understanding growth-defense tradeoffs in plants as well as what is known regard- ing the underlying molecular mechanisms. Specifically, we address evidence supporting the growth-defense tradeoff concept, as well as known interactions between defense signaling and growth signaling. Understanding the molecular basis of these tradeoffs in plants should provide a foundation for the development of breeding strategies that optimize the growth-defense balance to maximize crop yield to meet rising global food and biofuel demands.
基金supported by the National Natural Science Foundation of China(No.81774033 and No.81773736)the Hunan Provincial Department of Education-funded Scientific Research Project(No.18C0379 and No.19A378)。
文摘Objective:Our previous research showed that Naotaifang(a compound traditional Chinese herbal medicine)extract(NTE)has clinically beneficial effects on neurological improvement of patients with acute cerebral ischemia.In this study,we investigated whether NTE protected acute brain injury in rats and whether its effects on ferroptosis could be linked to the dysfunction of glutathione peroxidase 4(GPX4)and iron metabolism.Methods:We established an acute brain injury model of middle cerebral artery occlusion(MCAO)in rats,in which we could observe the accumulation of iron in neurons,as detected by Perl’s staining.Using assay kits,we measured expression levels of ferroptosis biomarkers,such as iron,glutathione(GSH),reactive oxygen species(ROS)and malonaldehyde(MDA);further the expression levels of transferrin receptor1(TFR1),divalent metal transporter 1(DMT1),solute carrier family 7 member 11(SLC7 A11)and GPX4 were determined using immunohistochemical analysis,real-time quantitative polymerase chain reaction and Western blot assays.Results:We found that treatment with NTE reduced the expression levels of TFR1 and DMT1,reduced ROS,MDA and iron accumulation and reduced neurobehavioral scores,relative to untreated MCAO rats.Treatment with NTE increased the expression levels of SLC7 A11,GPX4 and GSH,and the number of Nissl bodies in the MCAO rats.Conclusion:Taken together,our data suggest that acute cerebral ischemia induces neuronal ferroptosis and the effects of treating MCAO rats with NTE involved inhibition of ferroptosis through the TFR1/DMT1 and SCL7 A11/GPX4 pathways.
