Gastric cancer(GC)is the fourth most common cancer in the world with more than 70%of cases occur in the developing world.More than 50%of cases occur in Eastern Asia.GC is the second leading cause of cancer death in bo...Gastric cancer(GC)is the fourth most common cancer in the world with more than 70%of cases occur in the developing world.More than 50%of cases occur in Eastern Asia.GC is the second leading cause of cancer death in both sexes worldwide.In Asia,GC is the third most common cancer after breast and lung and is the second most common cause of cancer death after lung cancer.Although the incidence and mortality rates are slowly declining in many countries of Asia,GC still remains a significant public health problem.The incidence and mortality varies according to the geographic area in Asia.These variations are closely related to the prevalence of GC risk factors;especially Helicobacter pylori(H.pylori)and its molecular virulent characteristics.The gradual and consistent improvements in socioeconomic conditions in Asia have lowered the H.pylori seroprevalence rates leading to a reduction in the GC incidence.However,GC remains a significant public health and an economic burden in Asia.There has been no recent systemic review of GC incidence,mortality,and H.pylori molecular epidemiology in Asia.The aim of this report is to review the GC incidence,mortality,and linkage to H.pylori in Asia.展开更多
Recent data implicate oxidative stress as a mediator of pulmonary hypertension (PH) and of the associated pathological changes to the pulmonary vasculature and right ventricle (RV). Increases in reactive oxygen specie...Recent data implicate oxidative stress as a mediator of pulmonary hypertension (PH) and of the associated pathological changes to the pulmonary vasculature and right ventricle (RV). Increases in reactive oxygen species (ROS), altered redox state, and elevated oxidant stress have been demonstrated in the lungs and RV of several animal models of PH, including chronic hypoxia, monocrotaline toxicity, caveolin-1 knock-out mouse, and the transgenic Ren2 rat which overexpresses the mouse renin gene. Generation of ROS in these models is derived mostly from the activities of the nicotinamide adenine dinucleotide phosphate oxidases, xanthine oxidase, and uncoupled endothelial nitric oxide synthase. As disease progresses circulating monocytes and bone marrow-derived monocytic progenitor cells are attracted to and accumulate in the pulmonary vasculature. Once established, these inflammatory cells generate ROS and secrete mitogenic and fibrogenic cytokines that induce cell proliferation and fibrosis in the vascular wall resulting in progressive vascular remodeling. Deficiencies in antioxidant enzymes also contribute to pulmonary hypertensive states. Current therapies were developed to improve endothelial function, reduce pulmonary artery pressure, and slow the progression of vascular remodeling in the pulmonary vasculature by targeting deficiencies in either NO (PDE-type 5 inhibition) or PGI 2 (prostacyclin analogs), or excessive synthesis of ET-1 (ET receptor blockers) with the intent to improve patient clinical status and survival. New therapies may slow disease progression to some extent, but long term management has not been achieved and mortality is still high. Although little is known concerning the effects of current pulmonary arterial hypertension treatments on RV structure and function, interest in this area is increasing. Development of therapeutic strategies that simultaneously target pathology in the pulmonary vasculature and RV may be beneficial in reducing mortality associated with RV failure.展开更多
Endoscopic ultrasound(EUS) has revolutionized the diagnostic and therapeutic approach to patients with gastrointestinal disorders. Its application in patients with liver disease and portal hypertension is increasing. ...Endoscopic ultrasound(EUS) has revolutionized the diagnostic and therapeutic approach to patients with gastrointestinal disorders. Its application in patients with liver disease and portal hypertension is increasing. Patients with chronic liver disease are at risk for development of portal hypertension sequale such as ascites, spontaneous bacterial peritonitis and gastroesophageal varices. Bleeding esophageal and gastric varices are among the most common causes of mortality in patients with cirrhosis. Thus, early detection and treatment improve the outcome in this population. EUS can improve the detection and diagnosis of gastroesophageal varices and collateral veins and can provide endoscopic therapy of gastroesophageal varices such as EUS-guided sclerotherapy of esophageal collateral vessels and EUS-guided cynoacrylate(Glue) injection of gastric varices. EUS can also provide knowledge on the efficacy of pharmacotherapy of portal hypertension. Furthermore, EUS can provide assessment and prediction of variceal recurrence after endoscopic therapy and assessment of portal hemodynamics such as E-Flow and Doppler study of the azygous and portal veins. Moreover, EUS-guided fine needle aspiration may provide cytologic diagnosis of focal hepatic tumors andanalysis of free abdominal fluid.Using specialized EUSguided needle biopsy,a sample of liver tissue can be obtained to diagnose and evaluate for chronic liver disease.EUS-guided fine needle injection can be used to study portal vein pressure and hemodynamics,and potentially could be used to assist in exact measurement of portal vein pressure and placement of intrahepatic portosystemic shunt.展开更多
Alcohol abuse is the leading cause of liver related morbidity and mortality.Chronic or binge alcohol drinking causes hepatic steatosis which can develop to steatohepatitis,cirrhosis and ultimately hepatocellular carci...Alcohol abuse is the leading cause of liver related morbidity and mortality.Chronic or binge alcohol drinking causes hepatic steatosis which can develop to steatohepatitis,cirrhosis and ultimately hepatocellular carcinoma.The pathogenesis of alcoholic liver disease(ALD)is poorly characterized,however several recent studies point to a major role of mitochondria in this process.Mitochondria play a crucial role in cellular energy metabolism and in reactive species formation.Alcohol treatment causes mitochondrial DNA damage,lipid accumulation and oxidative stress.Studies in both animal models and in humans showed that alcohol administration causes changes in the mitochondrial morphology and function suggesting a role of these changes in the pathogenesis of ALD.We review recent findings on mechanisms by which alcohol negatively impacts mitochondrial biogenesis and function and we will discuss the specific intracellular pathways affected by alcohol consumption.Interestingly,recent findings indicate that a large number of mitochondrial proteins are acetylated and that mitochondrial proteins acetylation and sirtuins are modulated by alcohol.Un-derstanding the mechanisms behind alcohol mediated impaired mitochondrial biogenesis and function may help identify potential therapeutic targets for treating ALD in humans.展开更多
Alcohol consumption causes cellular injury. Recent developments indicate that ethanol induces epigenetic alterations, particularly acetylation, methylation of histones, and hypo- and hypermethylation of DNA. This has ...Alcohol consumption causes cellular injury. Recent developments indicate that ethanol induces epigenetic alterations, particularly acetylation, methylation of histones, and hypo- and hypermethylation of DNA. This has opened up a new area of interest in ethanol research and is providing novel insight into actions of ethanol at the nucleosomal level in relation to gene expression and patho-physiological consequences. The epigenetic effects are mainly attributable to ethanol metabolic stress (Emess), generated by the oxidative and non-oxidative metabolism of ethanol, and dysregulation of methionine metabolism. Epigenetic changes are important in ethanol-induced hepatic steatosis, fibrosis, carcinoma and gastrointestinal injury. This editorial highlights these new advances and its future potential.展开更多
Objective:To evaluate the antioxidant activity of aqueous extract of Atoringa oleifeta M.oleifera) young leaves by in vivo as well as in vitro assays.Methods:In vitro study included estimation of total phenolic,total ...Objective:To evaluate the antioxidant activity of aqueous extract of Atoringa oleifeta M.oleifera) young leaves by in vivo as well as in vitro assays.Methods:In vitro study included estimation of total phenolic,total ilavonol,total flavonoid and total antioxidant power(FRAP assay).Tn addition, in vivo study was done with the identified most effective dose of 200 nig/kg of its lyophilized powder on normal and diabetic rats.Its effect on different oxidative free radical scavenging enzymes,viz,superoxide dismutase(SOD),catalase(CAT),glutathione-S-transferase(GST),lipid peroxide(LPO) contents were measured.Results:Significant increase in activities of SOD.CAT, GST while,a decrease in LPO content was observed.Whereas,total phenolic,flavonoid and ilavonol contents in the extract were found to be 120 mg/g of CAK,40.5 mg/g of QEK and 12.12 mg/g of QE,respectively.On the other hand.FRAP assay results of M.oleifera leaves was(85.00±5.00)μM of Fe^+/g of extract powder.Conclusions:The significant antioxidant activities of M.oleifera leaves from both in vivo as well as in vitro studies suggests that the regular intake of its leaves through diet can protect normal as well as diabetic patients against oxidative damage.展开更多
The c-Jun NH2-terminal Kinase (JNK) pathway representsone sub-group of the mitogen-activated protein (MAP)kinases which plays an important role in variousinflammatory diseases states, including inflammatorybowel disea...The c-Jun NH2-terminal Kinase (JNK) pathway representsone sub-group of the mitogen-activated protein (MAP)kinases which plays an important role in variousinflammatory diseases states, including inflammatorybowel disease (IBD). Significant progress towardsunderstanding the function of the JNK signaling pathwayhas been achieved during the past few years. Blockadeof the JNK pathway with JNK inhibitors in animal modelsof IBD lead to resolution of intestinal inflammation.Current data suggest specific JNK inhibitors hold promiseas novel therapies in IBD.展开更多
Survival of children with chronic medical illnesses is leading to an increase in secondary osteoporosis due to impaired peak bone mass(PBM).Insulin-like growth factor type 1(IGF-1) levels correlate with the pattern of...Survival of children with chronic medical illnesses is leading to an increase in secondary osteoporosis due to impaired peak bone mass(PBM).Insulin-like growth factor type 1(IGF-1) levels correlate with the pattern of bone mass accrual and many chronic illnesses are associated with low IGF-1 levels.Reduced serum levels of IGF-1 minimally affect the integrity of the skeleton,whereas recent studies suggest that skeletal IGF-I regulates PBM.To determine the role of IGF-1 in postnatal bone mass accrual regardless of source,we established an inducible type 1 Igf receptor Cre/lox knockout mouse model,in which the type 1 Igf receptor was deleted inducibely in the mesenchymal stem cells(MSCs) from 3-7 weeks of age.The size of the mouse was not affected as knockout and wild type mice had similar body weights and nasoanal and femoral lengths.However,bone volume and trabecular bone thickness were decreased in the secondary spongiosa of female knockout mice relative to wild type controls,indicating that IGF-1 is critical for bone mass.IGF-1 signaling in MSCs in vitro has been implicated to be involved in both migration to the bone surface and differentiation into bone forming osteoblasts.To clarify the exact role of IGF-1 in bone,we found by immunohistochemical analysis that a similar number of Osterix-positive osteoprogenitors were on the bone perimeter,indicating migration of MSCs was not affected.Most importantly,56% fewer osteocalcin-positive mature osteoblasts were present on the bone perimeter in the secondary spongiosa in knockout mice versus wild type littermates.These in vivo data demonstrate that the primary role of skeletal IGF-1 is for the terminal differentiation of osteoprogenitors,but refute the role of IGF-1 in MSC migration in vivo.Additionally,these findings confirm that impaired IGF-1 signaling in bone MSCs is sufficient to impair bone mass acquisition.展开更多
AIM: To evaluate the effect of relaxing music during colonoscopy under low-dose conscious sedation, on patient satisfaction, scope insertion time and procedure duration, medication doses, and the perceived adequacy of...AIM: To evaluate the effect of relaxing music during colonoscopy under low-dose conscious sedation, on patient satisfaction, scope insertion time and procedure duration, medication doses, and the perceived adequacy of sedation and scope insertion difficulty on the part of the endoscopist. METHODS: One hundred and sixty-seven consecutive adult outpatients presenting for routine colonoscopy under low-dose conscious sedation were randomized to undergo their procedures either with music played during the procedure or no music played. RESULTS: There were no statistical differences between the two groups in terms of meperidine dose, midazolam dose, time to reach the cecum, total procedure time, endoscopist assessment of scope insertion difficulty, endoscopist assessment of adequacy of sedation, or the pain experience of the patients during their procedure. The music group did report significantly better overall procedure satisfaction as compared to the non music group on two of our three different scales. CONCLUSION: While music does not result in shortened procedure times, lower doses of sedative medications or perceived patient pain, the patients who have music playing during their procedures report modestly greater satisfaction with their procedures.展开更多
C-reactive protein(CRP) is a biomarker of inflammation.Increased plasma levels of CRP are associated with an increased risk of myocardial infarction.However,the correlation between plasma CRP concentration and atheros...C-reactive protein(CRP) is a biomarker of inflammation.Increased plasma levels of CRP are associated with an increased risk of myocardial infarction.However,the correlation between plasma CRP concentration and atherosclerotic plaque burden is poor.Based on these observations,it has been hypothesized that CRP increases the risk of myocardial infarction by promoting thrombosis.This article reviews available data that link enhanced CRP expression to increased risk of thrombosis,with a focus on the effects of CRP on hemostasis,platelet function,and fibrinolysis.Overall,the available data support the hypothesis that CRP is an important mechanistic link between inflammation and throm bosis.展开更多
AIM: To evaluate the glycated hemoglobin (HbA1c) determination methods and to determine fructosamine in patients with chronic hepatitis, compensated cirrhosis and in patients with chronic hepatitis treated with ribavi...AIM: To evaluate the glycated hemoglobin (HbA1c) determination methods and to determine fructosamine in patients with chronic hepatitis, compensated cirrhosis and in patients with chronic hepatitis treated with ribavirin.METHODS: HbA1c values were determined in 15 patients with compensated liver cirrhosis and in 20 patients with chronic hepatitis using the ion-exchange high performance liquid chromatography and the immunoassay methods. Fructosamine was determined using nitroblue tetrazolium.RESULTS: Forty percent of patients with liver cirrhosis had HbA1c results below the non-diabetic reference range by at least one HbA1c method, while fructosamine results were either within the reference range or elevated. Twenty percent of patients with chronic hepatitis (hepatic fibrosis) had HbA~ results below the non-diabetic reference range by at least one HbA~ method. In patients with chronic hepatitis treated with ribavirin, 50% of HbA^c results were below the non-diabetic reference using at least one of the HbA1c methods.CONCLUSION: Only evaluated in context with all liverfunction parameters as well as a red blood count includingreticulocytes, HbA1c results should be used in patients withadvanced liver disease. HbA1c and fructosamine measurements should be used with caution when evaluating long-term glucose control in patients with hepatic cirrhosis or in patients with chronic hepatitis and ribavirin treatment.展开更多
Originating from Wuhan in China,coronavirus disease 2019(COVID-19)spread globally within months and was declared a pandemic by World Health Organization in March 2020,making it one of the biggest healthcare calamities...Originating from Wuhan in China,coronavirus disease 2019(COVID-19)spread globally within months and was declared a pandemic by World Health Organization in March 2020,making it one of the biggest healthcare calamities of our time.As more data on COVID-19 infection became available,what was initially thought to be a simple respiratory illness was found to be more complex.Many extra-pulmonary manifestations are now frequently reported for COVID-19 in available literature,most commonly gastrointestinal and hepatopancreatobiliary manifestations.Due to early scarcity of data,extra pulmonary manifestations were initially overlooked and may have contributed to nosocomial spread of the infection.Practitioners,especially gastroenterologists,who frequently encounter patients with these symptoms,need to be aware of them.This can not only help minimize the nosocomial spread,ensure safety of provider but also help conserve already stretched-thin healthcare resources.A tremendous amount of COVID-19 related literature is getting added to the growing pool every day,making it difficult for providers to follow.The aim of our review is to summarize the available evidence for gastrointestinal and hepatopancreatobiliary manifestations of COVID-19.We here briefly discussed the possible pathophysiologic mechanism for these manifestations and summarized the recommendations put forward by multiple gastrointestinal societies regarding safe and effective clinical practice during the ongoing pandemic.展开更多
BACKGROUND The FAT cadherin family members(FAT1,FAT2,FAT3 and FAT4)are conserved tumor suppressors that are recurrently mutated in several types of human cancers,including colorectal carcinoma(CRC).AIM To characterize...BACKGROUND The FAT cadherin family members(FAT1,FAT2,FAT3 and FAT4)are conserved tumor suppressors that are recurrently mutated in several types of human cancers,including colorectal carcinoma(CRC).AIM To characterize the clinicopathologic features of CRC patients with somatic mutations in FAT cadherin family members.METHODS We analyzed 526 CRC cases from The Cancer Genome Atlas PanCancer Atlas dataset.CRC samples were subclassified into 2 groups based on the presence or absence of somatic mutations in FAT1,FAT2,FAT3 and FAT4.Individual clinicopathological data were collected after digital slide review.Statistical analysis was performed using t tests and chi-square tests.RESULTS This CRC study cohort had frequent mutations in the FAT1(10.5%),FAT2(11.2%),FAT3(15.4%)and FAT4(23.4%)genes.Two hundred CRC patients(38.0%)harbored somatic mutations in one or more of the FAT family genes and were grouped into the FAT mutated CRC subtype.The FAT-mutated CRC subtype was more commonly located on the right side of the colon(51.0%)than in the rest of the cohort(30.1%,P<0.001).It showed favorable clinicopathologic features,including a lower rate of positive lymph nodes(pN1-2:33.5%vs 46.4%,P=0.005),a lower rate of metastasis to another site or organ(pM1:7.5%vs 16.3%,P=0.006),and a trend toward an early tumor stage(pT1-2:25.0%vs 18.7%,P=0.093).FAT somatic mutations were significantly enriched in microsatellite instability CRC(28.0%vs 2.1%,P<0.001).However,FAT somatic mutations in microsatellite stable CRC demonstrated similar clinicopathologic behaviors,as well as a trend of a better diseasefree survival rate(hazard ratio=0.539;95%confidence interval:0.301-0.967;log-rank P=0.073).CONCLUSION FAT cadherin family genes are frequently mutated in CRC,and their mutation profile defines a subtype of CRC with favorable clinicopathologic characteristics.展开更多
BACKGROUND Music seems to be beneficial in multiple clinical areas.Colonoscopy is a stressful event for patients,especially with conscious sedation.Music during colonoscopy has been evaluated in multiple randomized co...BACKGROUND Music seems to be beneficial in multiple clinical areas.Colonoscopy is a stressful event for patients,especially with conscious sedation.Music during colonoscopy has been evaluated in multiple randomized controlled trials(RCTs)with varied results.Even meta-analyses on the subject over the years have yielded inconsistent conclusions.Therefore,we conducted an up-to-date meta-analysis regarding music during colonoscopy.AIM To assess the effects of music played during colonoscopy on patients’perspectives and sedation requirements.METHODS Multiple large databases were aggressively searched(November 2018).RCTs comparing music to without music during colonoscopy on adult patients were included.Pooled estimates were calculated for sedative medication doses,total procedure time,and patients’experience,willingness to repeat procedure,and pain scores using odds ratio(OR)and mean difference(MD)with random effects model.RESULTS Eleven studies(n=988)were included.Music during colonoscopy showed a statistically significant reduction in procedure times(MD:-2.3 min;95%CI:-4.13 to-0.47;P=0.01)and patients’pain(MD:-1.26;95%CI:-2.28 to-0.24;P=0.02)while improving patients’experience(MD:-1.11;95%CI:-1.7 to-0.53;P<0.01)as compared to no music.No statistically significant differences were observed between music and no music during colonoscopy for midazolam(MD:-0.4 mg;95%CI:-0.9 to 0.09;P=0.11),meperidine(MD:-3.06 mg;95%CI:-10.79 to 4.67;P=0.44),or patients’willingness to repeat the colonoscopy(OR:3.89;95%CI:0.76 to 19.97;P=0.1).CONCLUSION Music appears to improve overall patient experience while reducing procedure times and patient pain.Therefore,music,being a non-invasive intervention,should be strongly considered during colonoscopy.展开更多
The application of artificial intelligence(AI)using deep learning and machine learning approaches in modern medicine is rapidly expanding.Within the field of Gastroenterology,AI is being evaluated across a breadth of ...The application of artificial intelligence(AI)using deep learning and machine learning approaches in modern medicine is rapidly expanding.Within the field of Gastroenterology,AI is being evaluated across a breadth of clinical and diagnostic applications including identification of pathology,differentiation of disease processes,and even automated procedure report generation.Many pancreatic pathologies can have overlapping features creating a diagnostic dilemma that provides a window for AI-assisted improvement in current evaluation and diagnosis,particularly using endoscopic ultrasound.This topic highlight will review the basics of AI,history of AI in gastrointestinal endoscopy,and prospects for AI in the evaluation of autoimmune pancreatitis,pancreatic ductal adenocarcinoma,chronic pancreatitis and intraductal papillary mucinous neoplasm.展开更多
Reactive oxygen species(ROS)are key regulators of numerous subcellular,cellular,and systemic signals.They function in plants as an integral part of many different hormonal,physiological,and developmental pathways,as w...Reactive oxygen species(ROS)are key regulators of numerous subcellular,cellular,and systemic signals.They function in plants as an integral part of many different hormonal,physiological,and developmental pathways,as well as play a critical role in defense and acclimation responses to different biotic and abiotic conditions.Although many ROS imaging techniques have been developed and utilized in plants,a wholeplant imaging platform for the dynamic detection of ROS in mature plants is lacking.Here we report a robust and straightforward method for the whole-plant live imaging of ROS in mature plants grown in soil.This new method could be used to study local and systemic ROS signals in different genetic variants,conduct phenotyping studies to identify new pathways for ROS signaling,monitor the stress level of different plants and mutants,and unravel novel routes of ROS integration into stress,growth regulation,and development in plants.We demonstrate the utility of this new method for studying systemic ROS signals in different A rabidopsis mutants and wound responses in cereals such as wheat and corn.展开更多
AIM: To identify risk factors associated with esophageal cancer in Zambia and association between dietary intake and urinary 8-iso prostaglandin F2α(8-iso PGF2α).METHODS: We conducted a prospective, case control stu...AIM: To identify risk factors associated with esophageal cancer in Zambia and association between dietary intake and urinary 8-iso prostaglandin F2α(8-iso PGF2α).METHODS: We conducted a prospective, case control study at the University Teaching Hospital. Subjects included both individuals admitted to the hospital and those presenting for an outpatient upper endoscopy. Esophageal cancer cases were compared to age and sex-matched controls. Cases were defined as patients with biopsy proven esophageal cancer; controls were defined as subjects without endoscopic evidence ofesophageal cancer. Clinical and dietary data were collected using a standard questionnaire, developed a priori. Blood was collected for human immunodeficiency virus(HIV) serology. Urine was collected, and 8-iso PGF2α was measured primarily by enzyme-linked immunosorbent assay and expressed as a ratio to creatinine.RESULTS: Forty five controls(mean age 54.2 ± 15.3, 31 male) and 27 cases(mean age 54.6 ± 16.4, 17 males) were studied. Body mass index was lower in cases(median 16.8) than controls(median 23.2), P = 0.01. Histopathologically, 25/27(93%) were squamous cell carcinoma and 2/27(7%) adenocarcinoma. More cases smoked cigarettes(OR = 11.24, 95%CI: 1.37-92.4, P = 0.02) but alcohol consumption and HIV seropositivity did not differ significantly(P = 0.14 for both). Fruit, vegetables and fish consumption did not differ significantly between groups(P = 0.11, 0.12, and 0.10, respectively). Mean isoprostane level was significantly higher in cases(0.03 ng/mg creatinine) than controls(0.01 ng/mg creatinine)(OR = 2.35, 95%CI: 1.19-4.65, P = 0.014).CONCLUSION: Smoking and isoprostane levels were significantly associated with esophageal cancer in Zambians, but diet, HIV status, and alcohol consumption were not.展开更多
Glioblastoma(GBM)is the most common and most aggressive primary brain tumor in adults.The existence of a small population of stem-like tumor cells that efficiently propagate tumors and resist cytotoxic therapy is one ...Glioblastoma(GBM)is the most common and most aggressive primary brain tumor in adults.The existence of a small population of stem-like tumor cells that efficiently propagate tumors and resist cytotoxic therapy is one proposed mechanism leading to the resilient behavior of tumor cells and poor prognosis.In this study,we performed an in-depth analysis of the DNA methylation landscape in GBMderived cancer stem cells(GSCs).Parallel comparisons of primary tumors and GSC lines derived from these tumors with normal controls(a neural stem cell(NSC)line and normal brain tissue)identified groups of hyper- and hypomethylated genes that display a trend of either increasing or decreasing methylation levels in the order of controls,primary GBMs,and their counterpart GSC lines,respectively.Interestingly,concurrent promoter hypermethylation and gene body hypomethylation were observed in a subset of genes including MGMT,AJAP1 and PTPRN2.These unique DNA methylation signatures were also found in primary GBM-derived xenograft tumors indicating that they are not tissue culture-related epigenetic changes.Integration of GSC-specific epigenetic signatures with gene expression analysis further identified candidate tumor suppressor genes that are frequently down-regulated in GBMs such as SPINT2,NEFM and PENK.Forced re-expression of SPINT2 reduced glioma cell proliferative capacity,anchorage independent growth,cell motility,and tumor sphere formation in vitro.The results from this study demonstrate that GSCs possess unique epigenetic signatures that may play important roles in the pathogenesis of GBM.展开更多
Xanthomonas oryzae pv.oryzae(Xoo) is an important rice pathogen.This is a vascular pathogen entering the plant via the hydathodes causing rice bacterial blight.It has been known that most regulation of pathogenicity f...Xanthomonas oryzae pv.oryzae(Xoo) is an important rice pathogen.This is a vascular pathogen entering the plant via the hydathodes causing rice bacterial blight.It has been known that most regulation of pathogenicity factor F(RpfF) genes in Xanthomonas regulates virulence in response to the diffusible signal factor(DSF).The RpfF recognized as an attractive drug target in bacterial rice blight disease.In this study,we performed the gene-gene interaction of RpfF and pathway functional analysis.3 D structure of RpfF protein was predicted using a homology modelling tool Swiss-Model and refined by molecular dynamics(MD) simulation.The refined model protein was predicted structural assessment using various tools such as PROCHECK,ERRAT,and VERIFY-3 D.We have collected 2 500 rifampicin analogues from Zinc Database by virtual screening.The screened compounds were docked into the active site of the RpfF protein using AutoDock Vina in PyRx Virtual Screening Tool.Furthermore,docking result and in silico ADMET analysis described that the compounds ZINC03056414,ZINC03205310,ZINC08673779,ZINC09100848,ZINC09729566,ZINC11415953,ZINC12810788,ZINC24989313,ZINC27441787 and ZINC32739565 have best binding energies and less toxicity than reference compound.This study revealed that the active site residues such as HIS-118,HIS-147,THR-148,ARG-179,ASP-207,ARG-240 and THR-244 are key roles in the pathogenicity.It could be beneficial in the design of small molecule therapeutics or the treatment of rice bacterial blight disease.展开更多
Pancreatic ductal adenocarcinoma is one of the most aggressive and lethal cancers.Surgical resection is the only curable treatment option,but it is available for only a small fraction of patients at the time of diagno...Pancreatic ductal adenocarcinoma is one of the most aggressive and lethal cancers.Surgical resection is the only curable treatment option,but it is available for only a small fraction of patients at the time of diagnosis.With current therapeutic regimens,the average 5-year survival rate is less than 10%in pancreatic cancer patients.Immunotherapy has emerged as one of the most promising treatment options for multiple solid tumors of advanced stage.However,its clinical efficacy is suboptimal in most clinical trials on pancreatic cancer.Current studies have suggested that the tumor microenvironment is likely the underlying barrier affecting immunotherapy drug efficacy in pancreatic cancer.In this review,we discuss the role of the tumor microenvironment in pancreatic cancer and the latest advances in immunotherapy on pancreatic cancer.展开更多
文摘Gastric cancer(GC)is the fourth most common cancer in the world with more than 70%of cases occur in the developing world.More than 50%of cases occur in Eastern Asia.GC is the second leading cause of cancer death in both sexes worldwide.In Asia,GC is the third most common cancer after breast and lung and is the second most common cause of cancer death after lung cancer.Although the incidence and mortality rates are slowly declining in many countries of Asia,GC still remains a significant public health problem.The incidence and mortality varies according to the geographic area in Asia.These variations are closely related to the prevalence of GC risk factors;especially Helicobacter pylori(H.pylori)and its molecular virulent characteristics.The gradual and consistent improvements in socioeconomic conditions in Asia have lowered the H.pylori seroprevalence rates leading to a reduction in the GC incidence.However,GC remains a significant public health and an economic burden in Asia.There has been no recent systemic review of GC incidence,mortality,and H.pylori molecular epidemiology in Asia.The aim of this report is to review the GC incidence,mortality,and linkage to H.pylori in Asia.
文摘Recent data implicate oxidative stress as a mediator of pulmonary hypertension (PH) and of the associated pathological changes to the pulmonary vasculature and right ventricle (RV). Increases in reactive oxygen species (ROS), altered redox state, and elevated oxidant stress have been demonstrated in the lungs and RV of several animal models of PH, including chronic hypoxia, monocrotaline toxicity, caveolin-1 knock-out mouse, and the transgenic Ren2 rat which overexpresses the mouse renin gene. Generation of ROS in these models is derived mostly from the activities of the nicotinamide adenine dinucleotide phosphate oxidases, xanthine oxidase, and uncoupled endothelial nitric oxide synthase. As disease progresses circulating monocytes and bone marrow-derived monocytic progenitor cells are attracted to and accumulate in the pulmonary vasculature. Once established, these inflammatory cells generate ROS and secrete mitogenic and fibrogenic cytokines that induce cell proliferation and fibrosis in the vascular wall resulting in progressive vascular remodeling. Deficiencies in antioxidant enzymes also contribute to pulmonary hypertensive states. Current therapies were developed to improve endothelial function, reduce pulmonary artery pressure, and slow the progression of vascular remodeling in the pulmonary vasculature by targeting deficiencies in either NO (PDE-type 5 inhibition) or PGI 2 (prostacyclin analogs), or excessive synthesis of ET-1 (ET receptor blockers) with the intent to improve patient clinical status and survival. New therapies may slow disease progression to some extent, but long term management has not been achieved and mortality is still high. Although little is known concerning the effects of current pulmonary arterial hypertension treatments on RV structure and function, interest in this area is increasing. Development of therapeutic strategies that simultaneously target pathology in the pulmonary vasculature and RV may be beneficial in reducing mortality associated with RV failure.
文摘Endoscopic ultrasound(EUS) has revolutionized the diagnostic and therapeutic approach to patients with gastrointestinal disorders. Its application in patients with liver disease and portal hypertension is increasing. Patients with chronic liver disease are at risk for development of portal hypertension sequale such as ascites, spontaneous bacterial peritonitis and gastroesophageal varices. Bleeding esophageal and gastric varices are among the most common causes of mortality in patients with cirrhosis. Thus, early detection and treatment improve the outcome in this population. EUS can improve the detection and diagnosis of gastroesophageal varices and collateral veins and can provide endoscopic therapy of gastroesophageal varices such as EUS-guided sclerotherapy of esophageal collateral vessels and EUS-guided cynoacrylate(Glue) injection of gastric varices. EUS can also provide knowledge on the efficacy of pharmacotherapy of portal hypertension. Furthermore, EUS can provide assessment and prediction of variceal recurrence after endoscopic therapy and assessment of portal hemodynamics such as E-Flow and Doppler study of the azygous and portal veins. Moreover, EUS-guided fine needle aspiration may provide cytologic diagnosis of focal hepatic tumors andanalysis of free abdominal fluid.Using specialized EUSguided needle biopsy,a sample of liver tissue can be obtained to diagnose and evaluate for chronic liver disease.EUS-guided fine needle injection can be used to study portal vein pressure and hemodynamics,and potentially could be used to assist in exact measurement of portal vein pressure and placement of intrahepatic portosystemic shunt.
文摘Alcohol abuse is the leading cause of liver related morbidity and mortality.Chronic or binge alcohol drinking causes hepatic steatosis which can develop to steatohepatitis,cirrhosis and ultimately hepatocellular carcinoma.The pathogenesis of alcoholic liver disease(ALD)is poorly characterized,however several recent studies point to a major role of mitochondria in this process.Mitochondria play a crucial role in cellular energy metabolism and in reactive species formation.Alcohol treatment causes mitochondrial DNA damage,lipid accumulation and oxidative stress.Studies in both animal models and in humans showed that alcohol administration causes changes in the mitochondrial morphology and function suggesting a role of these changes in the pathogenesis of ALD.We review recent findings on mechanisms by which alcohol negatively impacts mitochondrial biogenesis and function and we will discuss the specific intracellular pathways affected by alcohol consumption.Interestingly,recent findings indicate that a large number of mitochondrial proteins are acetylated and that mitochondrial proteins acetylation and sirtuins are modulated by alcohol.Un-derstanding the mechanisms behind alcohol mediated impaired mitochondrial biogenesis and function may help identify potential therapeutic targets for treating ALD in humans.
文摘Alcohol consumption causes cellular injury. Recent developments indicate that ethanol induces epigenetic alterations, particularly acetylation, methylation of histones, and hypo- and hypermethylation of DNA. This has opened up a new area of interest in ethanol research and is providing novel insight into actions of ethanol at the nucleosomal level in relation to gene expression and patho-physiological consequences. The epigenetic effects are mainly attributable to ethanol metabolic stress (Emess), generated by the oxidative and non-oxidative metabolism of ethanol, and dysregulation of methionine metabolism. Epigenetic changes are important in ethanol-induced hepatic steatosis, fibrosis, carcinoma and gastrointestinal injury. This editorial highlights these new advances and its future potential.
基金National Medicinal Plants Board. Govt,of India,New Delhi,India for providing financial assistance in the form of Senior Research Fellowship to cam' out the present study
文摘Objective:To evaluate the antioxidant activity of aqueous extract of Atoringa oleifeta M.oleifera) young leaves by in vivo as well as in vitro assays.Methods:In vitro study included estimation of total phenolic,total ilavonol,total flavonoid and total antioxidant power(FRAP assay).Tn addition, in vivo study was done with the identified most effective dose of 200 nig/kg of its lyophilized powder on normal and diabetic rats.Its effect on different oxidative free radical scavenging enzymes,viz,superoxide dismutase(SOD),catalase(CAT),glutathione-S-transferase(GST),lipid peroxide(LPO) contents were measured.Results:Significant increase in activities of SOD.CAT, GST while,a decrease in LPO content was observed.Whereas,total phenolic,flavonoid and ilavonol contents in the extract were found to be 120 mg/g of CAK,40.5 mg/g of QEK and 12.12 mg/g of QE,respectively.On the other hand.FRAP assay results of M.oleifera leaves was(85.00±5.00)μM of Fe^+/g of extract powder.Conclusions:The significant antioxidant activities of M.oleifera leaves from both in vivo as well as in vitro studies suggests that the regular intake of its leaves through diet can protect normal as well as diabetic patients against oxidative damage.
文摘The c-Jun NH2-terminal Kinase (JNK) pathway representsone sub-group of the mitogen-activated protein (MAP)kinases which plays an important role in variousinflammatory diseases states, including inflammatorybowel disease (IBD). Significant progress towardsunderstanding the function of the JNK signaling pathwayhas been achieved during the past few years. Blockadeof the JNK pathway with JNK inhibitors in animal modelsof IBD lead to resolution of intestinal inflammation.Current data suggest specific JNK inhibitors hold promiseas novel therapies in IBD.
基金supported in part by the grants from the United States National Institute of Health NIDDK including T32DK07751 (JLC)the Diabetes Research and Training Center grant P60DK079637(JSF),and DK057501 and DK08098 (XC)
文摘Survival of children with chronic medical illnesses is leading to an increase in secondary osteoporosis due to impaired peak bone mass(PBM).Insulin-like growth factor type 1(IGF-1) levels correlate with the pattern of bone mass accrual and many chronic illnesses are associated with low IGF-1 levels.Reduced serum levels of IGF-1 minimally affect the integrity of the skeleton,whereas recent studies suggest that skeletal IGF-I regulates PBM.To determine the role of IGF-1 in postnatal bone mass accrual regardless of source,we established an inducible type 1 Igf receptor Cre/lox knockout mouse model,in which the type 1 Igf receptor was deleted inducibely in the mesenchymal stem cells(MSCs) from 3-7 weeks of age.The size of the mouse was not affected as knockout and wild type mice had similar body weights and nasoanal and femoral lengths.However,bone volume and trabecular bone thickness were decreased in the secondary spongiosa of female knockout mice relative to wild type controls,indicating that IGF-1 is critical for bone mass.IGF-1 signaling in MSCs in vitro has been implicated to be involved in both migration to the bone surface and differentiation into bone forming osteoblasts.To clarify the exact role of IGF-1 in bone,we found by immunohistochemical analysis that a similar number of Osterix-positive osteoprogenitors were on the bone perimeter,indicating migration of MSCs was not affected.Most importantly,56% fewer osteocalcin-positive mature osteoblasts were present on the bone perimeter in the secondary spongiosa in knockout mice versus wild type littermates.These in vivo data demonstrate that the primary role of skeletal IGF-1 is for the terminal differentiation of osteoprogenitors,but refute the role of IGF-1 in MSC migration in vivo.Additionally,these findings confirm that impaired IGF-1 signaling in bone MSCs is sufficient to impair bone mass acquisition.
文摘AIM: To evaluate the effect of relaxing music during colonoscopy under low-dose conscious sedation, on patient satisfaction, scope insertion time and procedure duration, medication doses, and the perceived adequacy of sedation and scope insertion difficulty on the part of the endoscopist. METHODS: One hundred and sixty-seven consecutive adult outpatients presenting for routine colonoscopy under low-dose conscious sedation were randomized to undergo their procedures either with music played during the procedure or no music played. RESULTS: There were no statistical differences between the two groups in terms of meperidine dose, midazolam dose, time to reach the cecum, total procedure time, endoscopist assessment of scope insertion difficulty, endoscopist assessment of adequacy of sedation, or the pain experience of the patients during their procedure. The music group did report significantly better overall procedure satisfaction as compared to the non music group on two of our three different scales. CONCLUSION: While music does not result in shortened procedure times, lower doses of sedative medications or perceived patient pain, the patients who have music playing during their procedures report modestly greater satisfaction with their procedures.
基金Supported by Merit Review Award from the Department of Veterans Affairs,research grants from the Missouri Life Sciences Research Board and NIH,No. HL57346
文摘C-reactive protein(CRP) is a biomarker of inflammation.Increased plasma levels of CRP are associated with an increased risk of myocardial infarction.However,the correlation between plasma CRP concentration and atherosclerotic plaque burden is poor.Based on these observations,it has been hypothesized that CRP increases the risk of myocardial infarction by promoting thrombosis.This article reviews available data that link enhanced CRP expression to increased risk of thrombosis,with a focus on the effects of CRP on hemostasis,platelet function,and fibrinolysis.Overall,the available data support the hypothesis that CRP is an important mechanistic link between inflammation and throm bosis.
文摘AIM: To evaluate the glycated hemoglobin (HbA1c) determination methods and to determine fructosamine in patients with chronic hepatitis, compensated cirrhosis and in patients with chronic hepatitis treated with ribavirin.METHODS: HbA1c values were determined in 15 patients with compensated liver cirrhosis and in 20 patients with chronic hepatitis using the ion-exchange high performance liquid chromatography and the immunoassay methods. Fructosamine was determined using nitroblue tetrazolium.RESULTS: Forty percent of patients with liver cirrhosis had HbA1c results below the non-diabetic reference range by at least one HbA1c method, while fructosamine results were either within the reference range or elevated. Twenty percent of patients with chronic hepatitis (hepatic fibrosis) had HbA~ results below the non-diabetic reference range by at least one HbA~ method. In patients with chronic hepatitis treated with ribavirin, 50% of HbA^c results were below the non-diabetic reference using at least one of the HbA1c methods.CONCLUSION: Only evaluated in context with all liverfunction parameters as well as a red blood count includingreticulocytes, HbA1c results should be used in patients withadvanced liver disease. HbA1c and fructosamine measurements should be used with caution when evaluating long-term glucose control in patients with hepatic cirrhosis or in patients with chronic hepatitis and ribavirin treatment.
文摘Originating from Wuhan in China,coronavirus disease 2019(COVID-19)spread globally within months and was declared a pandemic by World Health Organization in March 2020,making it one of the biggest healthcare calamities of our time.As more data on COVID-19 infection became available,what was initially thought to be a simple respiratory illness was found to be more complex.Many extra-pulmonary manifestations are now frequently reported for COVID-19 in available literature,most commonly gastrointestinal and hepatopancreatobiliary manifestations.Due to early scarcity of data,extra pulmonary manifestations were initially overlooked and may have contributed to nosocomial spread of the infection.Practitioners,especially gastroenterologists,who frequently encounter patients with these symptoms,need to be aware of them.This can not only help minimize the nosocomial spread,ensure safety of provider but also help conserve already stretched-thin healthcare resources.A tremendous amount of COVID-19 related literature is getting added to the growing pool every day,making it difficult for providers to follow.The aim of our review is to summarize the available evidence for gastrointestinal and hepatopancreatobiliary manifestations of COVID-19.We here briefly discussed the possible pathophysiologic mechanism for these manifestations and summarized the recommendations put forward by multiple gastrointestinal societies regarding safe and effective clinical practice during the ongoing pandemic.
文摘BACKGROUND The FAT cadherin family members(FAT1,FAT2,FAT3 and FAT4)are conserved tumor suppressors that are recurrently mutated in several types of human cancers,including colorectal carcinoma(CRC).AIM To characterize the clinicopathologic features of CRC patients with somatic mutations in FAT cadherin family members.METHODS We analyzed 526 CRC cases from The Cancer Genome Atlas PanCancer Atlas dataset.CRC samples were subclassified into 2 groups based on the presence or absence of somatic mutations in FAT1,FAT2,FAT3 and FAT4.Individual clinicopathological data were collected after digital slide review.Statistical analysis was performed using t tests and chi-square tests.RESULTS This CRC study cohort had frequent mutations in the FAT1(10.5%),FAT2(11.2%),FAT3(15.4%)and FAT4(23.4%)genes.Two hundred CRC patients(38.0%)harbored somatic mutations in one or more of the FAT family genes and were grouped into the FAT mutated CRC subtype.The FAT-mutated CRC subtype was more commonly located on the right side of the colon(51.0%)than in the rest of the cohort(30.1%,P<0.001).It showed favorable clinicopathologic features,including a lower rate of positive lymph nodes(pN1-2:33.5%vs 46.4%,P=0.005),a lower rate of metastasis to another site or organ(pM1:7.5%vs 16.3%,P=0.006),and a trend toward an early tumor stage(pT1-2:25.0%vs 18.7%,P=0.093).FAT somatic mutations were significantly enriched in microsatellite instability CRC(28.0%vs 2.1%,P<0.001).However,FAT somatic mutations in microsatellite stable CRC demonstrated similar clinicopathologic behaviors,as well as a trend of a better diseasefree survival rate(hazard ratio=0.539;95%confidence interval:0.301-0.967;log-rank P=0.073).CONCLUSION FAT cadherin family genes are frequently mutated in CRC,and their mutation profile defines a subtype of CRC with favorable clinicopathologic characteristics.
文摘BACKGROUND Music seems to be beneficial in multiple clinical areas.Colonoscopy is a stressful event for patients,especially with conscious sedation.Music during colonoscopy has been evaluated in multiple randomized controlled trials(RCTs)with varied results.Even meta-analyses on the subject over the years have yielded inconsistent conclusions.Therefore,we conducted an up-to-date meta-analysis regarding music during colonoscopy.AIM To assess the effects of music played during colonoscopy on patients’perspectives and sedation requirements.METHODS Multiple large databases were aggressively searched(November 2018).RCTs comparing music to without music during colonoscopy on adult patients were included.Pooled estimates were calculated for sedative medication doses,total procedure time,and patients’experience,willingness to repeat procedure,and pain scores using odds ratio(OR)and mean difference(MD)with random effects model.RESULTS Eleven studies(n=988)were included.Music during colonoscopy showed a statistically significant reduction in procedure times(MD:-2.3 min;95%CI:-4.13 to-0.47;P=0.01)and patients’pain(MD:-1.26;95%CI:-2.28 to-0.24;P=0.02)while improving patients’experience(MD:-1.11;95%CI:-1.7 to-0.53;P<0.01)as compared to no music.No statistically significant differences were observed between music and no music during colonoscopy for midazolam(MD:-0.4 mg;95%CI:-0.9 to 0.09;P=0.11),meperidine(MD:-3.06 mg;95%CI:-10.79 to 4.67;P=0.44),or patients’willingness to repeat the colonoscopy(OR:3.89;95%CI:0.76 to 19.97;P=0.1).CONCLUSION Music appears to improve overall patient experience while reducing procedure times and patient pain.Therefore,music,being a non-invasive intervention,should be strongly considered during colonoscopy.
文摘The application of artificial intelligence(AI)using deep learning and machine learning approaches in modern medicine is rapidly expanding.Within the field of Gastroenterology,AI is being evaluated across a breadth of clinical and diagnostic applications including identification of pathology,differentiation of disease processes,and even automated procedure report generation.Many pancreatic pathologies can have overlapping features creating a diagnostic dilemma that provides a window for AI-assisted improvement in current evaluation and diagnosis,particularly using endoscopic ultrasound.This topic highlight will review the basics of AI,history of AI in gastrointestinal endoscopy,and prospects for AI in the evaluation of autoimmune pancreatitis,pancreatic ductal adenocarcinoma,chronic pancreatitis and intraductal papillary mucinous neoplasm.
基金the National Science Foundation(IOS-1353886,IOS-1063287,MCB-1613462)and the University of Missouri.
文摘Reactive oxygen species(ROS)are key regulators of numerous subcellular,cellular,and systemic signals.They function in plants as an integral part of many different hormonal,physiological,and developmental pathways,as well as play a critical role in defense and acclimation responses to different biotic and abiotic conditions.Although many ROS imaging techniques have been developed and utilized in plants,a wholeplant imaging platform for the dynamic detection of ROS in mature plants is lacking.Here we report a robust and straightforward method for the whole-plant live imaging of ROS in mature plants grown in soil.This new method could be used to study local and systemic ROS signals in different genetic variants,conduct phenotyping studies to identify new pathways for ROS signaling,monitor the stress level of different plants and mutants,and unravel novel routes of ROS integration into stress,growth regulation,and development in plants.We demonstrate the utility of this new method for studying systemic ROS signals in different A rabidopsis mutants and wound responses in cereals such as wheat and corn.
基金Supported by NIH grant,No.R24TW007988the American Relief and Recovery Actthe Siteman Comprehensive Cancer Center NCI Cancer Center Support Grant,P30 CA091842
文摘AIM: To identify risk factors associated with esophageal cancer in Zambia and association between dietary intake and urinary 8-iso prostaglandin F2α(8-iso PGF2α).METHODS: We conducted a prospective, case control study at the University Teaching Hospital. Subjects included both individuals admitted to the hospital and those presenting for an outpatient upper endoscopy. Esophageal cancer cases were compared to age and sex-matched controls. Cases were defined as patients with biopsy proven esophageal cancer; controls were defined as subjects without endoscopic evidence ofesophageal cancer. Clinical and dietary data were collected using a standard questionnaire, developed a priori. Blood was collected for human immunodeficiency virus(HIV) serology. Urine was collected, and 8-iso PGF2α was measured primarily by enzyme-linked immunosorbent assay and expressed as a ratio to creatinine.RESULTS: Forty five controls(mean age 54.2 ± 15.3, 31 male) and 27 cases(mean age 54.6 ± 16.4, 17 males) were studied. Body mass index was lower in cases(median 16.8) than controls(median 23.2), P = 0.01. Histopathologically, 25/27(93%) were squamous cell carcinoma and 2/27(7%) adenocarcinoma. More cases smoked cigarettes(OR = 11.24, 95%CI: 1.37-92.4, P = 0.02) but alcohol consumption and HIV seropositivity did not differ significantly(P = 0.14 for both). Fruit, vegetables and fish consumption did not differ significantly between groups(P = 0.11, 0.12, and 0.10, respectively). Mean isoprostane level was significantly higher in cases(0.03 ng/mg creatinine) than controls(0.01 ng/mg creatinine)(OR = 2.35, 95%CI: 1.19-4.65, P = 0.014).CONCLUSION: Smoking and isoprostane levels were significantly associated with esophageal cancer in Zambians, but diet, HIV status, and alcohol consumption were not.
基金supported in part by the National Institute of Health(Grant Nos.CA134304 and DA025779 to H.S., NS073611 and NS076759 to J.L.)
文摘Glioblastoma(GBM)is the most common and most aggressive primary brain tumor in adults.The existence of a small population of stem-like tumor cells that efficiently propagate tumors and resist cytotoxic therapy is one proposed mechanism leading to the resilient behavior of tumor cells and poor prognosis.In this study,we performed an in-depth analysis of the DNA methylation landscape in GBMderived cancer stem cells(GSCs).Parallel comparisons of primary tumors and GSC lines derived from these tumors with normal controls(a neural stem cell(NSC)line and normal brain tissue)identified groups of hyper- and hypomethylated genes that display a trend of either increasing or decreasing methylation levels in the order of controls,primary GBMs,and their counterpart GSC lines,respectively.Interestingly,concurrent promoter hypermethylation and gene body hypomethylation were observed in a subset of genes including MGMT,AJAP1 and PTPRN2.These unique DNA methylation signatures were also found in primary GBM-derived xenograft tumors indicating that they are not tissue culture-related epigenetic changes.Integration of GSC-specific epigenetic signatures with gene expression analysis further identified candidate tumor suppressor genes that are frequently down-regulated in GBMs such as SPINT2,NEFM and PENK.Forced re-expression of SPINT2 reduced glioma cell proliferative capacity,anchorage independent growth,cell motility,and tumor sphere formation in vitro.The results from this study demonstrate that GSCs possess unique epigenetic signatures that may play important roles in the pathogenesis of GBM.
文摘Xanthomonas oryzae pv.oryzae(Xoo) is an important rice pathogen.This is a vascular pathogen entering the plant via the hydathodes causing rice bacterial blight.It has been known that most regulation of pathogenicity factor F(RpfF) genes in Xanthomonas regulates virulence in response to the diffusible signal factor(DSF).The RpfF recognized as an attractive drug target in bacterial rice blight disease.In this study,we performed the gene-gene interaction of RpfF and pathway functional analysis.3 D structure of RpfF protein was predicted using a homology modelling tool Swiss-Model and refined by molecular dynamics(MD) simulation.The refined model protein was predicted structural assessment using various tools such as PROCHECK,ERRAT,and VERIFY-3 D.We have collected 2 500 rifampicin analogues from Zinc Database by virtual screening.The screened compounds were docked into the active site of the RpfF protein using AutoDock Vina in PyRx Virtual Screening Tool.Furthermore,docking result and in silico ADMET analysis described that the compounds ZINC03056414,ZINC03205310,ZINC08673779,ZINC09100848,ZINC09729566,ZINC11415953,ZINC12810788,ZINC24989313,ZINC27441787 and ZINC32739565 have best binding energies and less toxicity than reference compound.This study revealed that the active site residues such as HIS-118,HIS-147,THR-148,ARG-179,ASP-207,ARG-240 and THR-244 are key roles in the pathogenicity.It could be beneficial in the design of small molecule therapeutics or the treatment of rice bacterial blight disease.
文摘Pancreatic ductal adenocarcinoma is one of the most aggressive and lethal cancers.Surgical resection is the only curable treatment option,but it is available for only a small fraction of patients at the time of diagnosis.With current therapeutic regimens,the average 5-year survival rate is less than 10%in pancreatic cancer patients.Immunotherapy has emerged as one of the most promising treatment options for multiple solid tumors of advanced stage.However,its clinical efficacy is suboptimal in most clinical trials on pancreatic cancer.Current studies have suggested that the tumor microenvironment is likely the underlying barrier affecting immunotherapy drug efficacy in pancreatic cancer.In this review,we discuss the role of the tumor microenvironment in pancreatic cancer and the latest advances in immunotherapy on pancreatic cancer.
