Gastric cancer is one of the leading causes of cancer mortality in the world. Aberrant expression of microRNAs (miRNAs) is the hallmark of this disease. MiRNAs are endogenous non-coding RNAs that are involved in many ...Gastric cancer is one of the leading causes of cancer mortality in the world. Aberrant expression of microRNAs (miRNAs) is the hallmark of this disease. MiRNAs are endogenous non-coding RNAs that are involved in many biological processes (e.g., cell proliferation, differentiation, apoptosis, invasion and development) through gene repression. Deregulation of miRNA expression in gastric tumors and cancer cell lines have been documented to contribute in tumorigenesis, and the expression signature may correlate with different cancer types and clinicopathological features. Here, we summarized the updated gastric cancer-associated miRNAs and the downstream targets in the process of tumorigenesis. Recently, many researchers make use of the miRNA microarray platform to profile miRNA expression in gastric cancer and correlated with different clinical parameters. Its application on cancer diagnosis, prognosis and predicting treatment response rate are still underway and needs further investigation. Emerging roles of miRNAs with oncogenic or tumor suppressive properties in gastric tumorigenesis were discussed. Epigenetic silencing of miRNA by hypermethylation of promoter CpG island was also observed in gastric cancer. However, detailed mechanisms of how miRNAs regulate gene expression in gastric cancer has not been well studied. In this review, we highlight the up-to-date findings on the deregulated miRNAs in gastric cancer, and the potential use of miRNA in the clinical settings, such as diagnostic/prognostic markers and chemotherapeutic tools.展开更多
Objective To investigate the protective effects of putative AGEs （advanced glycation endproducts） inhibitor salidroside against aging in an accelerated mouse aging model induced by D-galactose. Methods A group of 5-...Objective To investigate the protective effects of putative AGEs （advanced glycation endproducts） inhibitor salidroside against aging in an accelerated mouse aging model induced by D-galactose. Methods A group of 5-month-old C57BL/6J mice were treated daily with D-galactose, D-galactose combined with salidroside, salidroside alone, and control buffer for 8 weeks. At the end of the treatment, serum AGEs levels, neurological activities, expression of glial fibrillary acidic protein （GFAP） and neurotrophin-3 （NT-3） in the cerebral cortex, as well as lymphocyte proliferation and IL-2 production were determined. Results D-galactose induced mouse aging model was developed as described before. As expected, salidroside blocked D-galactose induced increase of serum AGEs levels. It also reversed D-galactose induced aging effects in neural and immune system, as evidenced by improving motor activity, increasing memory latency time, and enhancing lymphocyte mitogenesis and interleukin-2 （IL-2） production. Furthermore, elevated expression of GFAP and NT-3 in the aged model mice was also reduced upon salidroside treatment. Conclusion Salidroside inhibits AGEs formation in vivo, which at least partially contributes to its anti-aging effect in D-galactose induced aging model.展开更多
Developing realistic soil carbon （C） sequestration strategies for China＇s sustainable agriculture relies on accurate estimates of the amount, retention and turnover rates of C stored in paddy soils. Available C est...Developing realistic soil carbon （C） sequestration strategies for China＇s sustainable agriculture relies on accurate estimates of the amount, retention and turnover rates of C stored in paddy soils. Available C estimates to date are predominantly for the tilled and flood-irrigated surface topsoil （ca. 30 cm）. Such estimates cannot be used to extrapolate to soil depths of 100 cm since soil organic carbon （SOC） generally shows a sharp decrease with depth. In this research, composite soil samples were collected at several depths to 100 cm from three representative paddy soils in the Taihu Lake region, China. Soil organic carbon distribution in the profiles and in aggregate-size fractions was determined. Results showed that while SOC decreased exponentially with depth to 100 cm, a substantial proportion of the total SOC （30%-40%） is stored below the 30 cm depth. In the carbon-enriched paddy topsoils, SOC was found to accumulate preferentially in the 2-0.25 and 0.25-0.02 mm aggregate size fractions. δ^13C analysis of the coarse micro-aggregate fraction showed that the high degree of C stratification in the paddy topsoil was in agreement with the occurrence of lighter δ^1313C in the upper 30 cm depth. These results suggest that SOC stratification within profiles varies with different pedogenetical types of paddy soils with regards to clay and iron oxyhydrates distributions. Sand-sized fractions of aggregates in paddy soil systems may play a very important role in carbon sequestration and turnover, dissimilar to other studied agricultural systems.展开更多
AIM： To study the association of three common ABCB11 and ABCC2 polymorphisms （ABCB11： 1331T〉C→V444A; ABCC2： 3563T〉A → V1188E and 4544G 〉A → C1515Y） with intrahepatic cholestasis of pregnancy （ICP） and con...AIM： To study the association of three common ABCB11 and ABCC2 polymorphisms （ABCB11： 1331T〉C→V444A; ABCC2： 3563T〉A → V1188E and 4544G 〉A → C1515Y） with intrahepatic cholestasis of pregnancy （ICP） and contraceptive-induced cholestasis （CIC）. METHODS： ABCB11 and ABCC2 genotyping data were available from four CIC patients and from 42 and 33 ICP patients, respectively. Allele-frequencies of the studied polymorphisms were compared with those in healthy pregnant controls and Caucasian individuals. Furthermore, serum bile acid levels were correlated with the presence or absence of the 1331 C allele. RESULTS： The ABCB11 1331T〉C polymorphism was significantly more frequent in cholestatic patients than in pregnant controls： C allele 76.2% （CI, 58.0-94.4） vs 51.3% （CI 35.8-66.7）, respectively （P = 0.0007）; and CC allele 57.1% （CI 36.0-78.3） vs 20% （CI 7.6-32.4）, respectively （P = 0.0065）. All four CIC patients were homozygous carriers of the C allele. In contrast, none of the studied ABCC2 polymorphism was overrepresented in ICP or CIC patients. Higher serum bile acid levels were found in carriers of the 1331CC genotype compared to carriers of the TT genotype. CONCLUSION： Our data support a role for the ABCB11 1331T〉C polymorphism as a susceptibility factor for the development of estrogen-induced cholestasis, whereas no such association was found for ABCC2. Serum bile acid and 7-glutamyl transferase levels might help to distinguish ABCB4- and ABCB11-related forms of ICP and CIC.展开更多
AIM: To investigate Fusobacterium nucleatum (F. nucleatum) abundance in colorectal cancer (CRC) tissues and its association with CRC invasiveness in Chinese patients.METHODS: The resected cancer and adjacent normal ti...AIM: To investigate Fusobacterium nucleatum (F. nucleatum) abundance in colorectal cancer (CRC) tissues and its association with CRC invasiveness in Chinese patients.METHODS: The resected cancer and adjacent normal tissues (10 cm beyond cancer margins) from 101 consecutive patients with CRC were collected. Fluorescent quantitative polymerase chain reaction (FQ-PCR) was applied to detect F. nucleatum in CRC and normal tissues. The difference of F. nucleatum abundance between cancer and normal tissues and the relationship of F. nucleatum abundance with clinical variables were evaluated. Fluorescence in situ hybridization (FISH) analysis was performed on 22 CRC tissues with the highest F. nucleatum abundance by FQ-PCR testing to confirm FQ-PCR results.RESULTS: The median abundance of F. nucleatum in CRC tissues [0.242 (0.178-0.276)] was significantly higher than that in normal controls [0.050 (0.023-0.067)] (P < 0.001). F. nucleatum was over-represented in 88/101 (87.1%) CRC samples. The abundance of F. nucleatum determined by 2<sup>-ΔCT</sup> was significantly greater in tumor samples [0.242 (0.178, 0.276)] than in normal controls [0.050 (0.023, 0.067)] (P < 0.001). The frequency of patients with lymph node metastases was higher in the over-abundance group [52/88 (59.1%)] than in the under-abundance group [0/13 (0%)] (P < 0.005). No significant association of F. nucleatum with other clinico-pathological variables was observed (P > 0.05). FISH analysis also found more F. nucleatum in CRC than in normal tissues (median number 6, 25<sup>th</sup> 3, 75<sup>th</sup> 10 vs 2, 25<sup>th</sup> 1, 75<sup>th</sup> 5) (P < 0.01).CONCLUSION: F. nucleatum was enriched in CRC tissues and associated with CRC development and metastasis.展开更多
Arabidopsis MSI1 has fundamental functions in plant development. MSI1 is a subunit of Polycomb group protein complexes and Chromatin assembly factor 1, and it interacts with the Retinoblastoma-related protein 1. Alter...Arabidopsis MSI1 has fundamental functions in plant development. MSI1 is a subunit of Polycomb group protein complexes and Chromatin assembly factor 1, and it interacts with the Retinoblastoma-related protein 1. Altered levels of MSI1 result in pleiotropic phenotypes, reflecting the complexity of MSI1 protein functions. In order to uncover additional functions of MSI1, we performed transcriptional profiling of wild-type and plants with highly reduced MSI1 levels （msil-cs）. Surprisingly, the known functions of MSI1 could only account for a minor part of the transcriptional changes in msil-cs plants. One of the most striking unexpected observations was the up-regulation of a subset of ABA-responsive genes eliciting the response to drought and salt stress. We report that MSI1 can bind to the chromatin of the drought-inducible downstream target RD20 and suggest a new role for MSI1 in the negative regulation of the Arabidopsis drought-stress response.展开更多
A severe spinal cord involvement may rarely occur in patients with cirrhosis and other chronic liver diseases;this complication is usually associated with overt liver failure and surgical or spontaneous porto-systemic...A severe spinal cord involvement may rarely occur in patients with cirrhosis and other chronic liver diseases;this complication is usually associated with overt liver failure and surgical or spontaneous porto-systemic shunt.Hepatic myelopathy(HM)is characterized by progressive weakness and spasticity of the lower extremities,while sensory and sphincter disturbances have rarely been described and are usually less important.The diagnosis is assigned in the appropriate clinical setting on clinical grounds after the exclusion of other clinical entities leading to spastic paraparesis.Magnetic resonance imaging is often unremarkable;however,also intracerebral corticospinal tract abnor-malities have been reported recently.The study of motor evoked potentials may disclose central conduction abnormalities even before HM is clinically manifest.HM responds poorly to blood ammonia-lowering and other conservative medical therapy.Liver transplantation represents a potentially definitive treatment for HM in patients with decompensated cirrhosis of Child-Pugh B and C grades.Other surgical treatment options in HM include surgical ligation,shunt reduction,or occlusion by interventional procedures.展开更多
Liver cancer is the sixth most common cancer worldwide,and the third most common cause of cancer-related death.Hepatocellular carcinoma(HCC),which accounts for more than 90%of primary liver cancers,is an important pub...Liver cancer is the sixth most common cancer worldwide,and the third most common cause of cancer-related death.Hepatocellular carcinoma(HCC),which accounts for more than 90%of primary liver cancers,is an important public health problem.In addition to cirrhosis caused by hepatitis B viral(HBV)or hepatitis C viral(HCV)infection,non-alcoholic fatty liver disease(NAFLD)is becoming a major risk factor for liver cancer because of the prevalence of obesity.Non-alcoholic steatohepatitis(NASH)will likely become the leading indication for liver transplantation in the future.It is well recognized that gut microbiota is a key environmental factor in the pathogenesis of liver disease and cancer.The interplay between gut microbiota and liver disease has been investigated in animal and clinical studies.In this article,we summarize the roles of gut microbiota in the development of liver disease as well as gut microbiota-targeted therapies.展开更多
Background:Probiotic VSL#3 is used to treat ulcerative colitis.This study examines the effect of VSL#3 in non-alcoholic steatohepatitis(NASH)that has liver carcinogenic potential.Methods:Western diet(WD)-fed wild-type...Background:Probiotic VSL#3 is used to treat ulcerative colitis.This study examines the effect of VSL#3 in non-alcoholic steatohepatitis(NASH)that has liver carcinogenic potential.Methods:Western diet(WD)-fed wild-type(WT)mice that do not have hepatic inflammation with lymphocyte infiltration and carcinogenic potential were used for baseline comparison.Age-,sex-,and diet-matched bile acid(BA)receptor farnesoid X receptor(FXR)knockout(KO)mice,which developed severe NASH and had the potential for liver cancer development,were supplemented with and without VSL#3 for 7 months.All the mice were euthanized when they were 10 months old.Results:Supplementation with VSL#3 completely abolished hepatic lymphocyte infiltration,reduced hepatic fat content,and improved insulin sensitivity in WD-fed FXR KO mice.In addition,VSL#3 normalized dysregulated BA homoeostasis by inhibiting the classical BA synthesis pathway,inducing the alternative BA pathway,and activating ileal G-protein coupled BA receptor 1(GPBAR1)-regulated signaling.Moreover,VSL#3 reconstructed the gut microbiota by reducing Bacteroidaceae,Porphyromonadaceae,and Helicobacteraceae as well as increasing Lachnospiraceae.Further,VSL#3 enriched the abundance of Ruminococcus and Faecalibacterium,which generate butyrate,at the genus level.It also increased the copy number of the butyrate-producing genes bcoA and buk,suggesting their anti-inflammatory and metabolic effects.Conclusions:VSL#3 is useful in reversing NASH that occurred due to dysregulated BA synthesis and dysbiosis,suggesting its potential in liver cancer prevention.展开更多
Despite the tremendous efforts for improving therapeutics of lung cancer patients,its prognosis remains disappoint-ing.This can be largely attributed to the lack of comprehensive understanding of drug resistance leadi...Despite the tremendous efforts for improving therapeutics of lung cancer patients,its prognosis remains disappoint-ing.This can be largely attributed to the lack of comprehensive understanding of drug resistance leading to insuf-ficient development of effective therapeutics in clinic.Based on the current progresses of lung cancer research,we classify drug resistance mechanisms into three different levels:molecular,cellular and pathological level.All these three levels have significantly contributed to the acquisition and evolution of drug resistance in clinic.Our under-standing on drug resistance mechanisms has begun to change the way of clinical practice and improve patient prognosis.In this review,we focus on discussing the pathological changes linking to drug resistance as this has been largely overlooked in the past decades.展开更多
Peritoneal carcinomatosis (PC) is one manifestation of metastatic colorectal cancer (CRC). Tumor growth on intestinal surfaces and associated fluid accumulation eventually result in bowel obstruction and incapacitatin...Peritoneal carcinomatosis (PC) is one manifestation of metastatic colorectal cancer (CRC). Tumor growth on intestinal surfaces and associated fluid accumulation eventually result in bowel obstruction and incapacitating levels of ascites, which profoundly affect the quality of life for affected patients. PC appears resistant to traditional 5-fluorouracil-based chemotherapy, and surgery was formerly reserved for palliative purposes only. In the absence of effective treatment, the histori-cal prognosis for these patients was extremely poor, with an invariably fatal outcome. These poor outcomes likely explain why PC secondary to CRC has received little attention from oncologic researchers. Thus, data are lacking regarding incidence, clinical disease course, and accurate treatment evaluation for patients with PC. Recently, population-based studies have revealed that PC occurs relatively frequently among patients withCRC. Risk factors for developing PC have been identi-fied:right-sided tumor, advanced T-stage, advanced N-stage, poor differentiation grade, and younger age at diagnosis. During the past decade, both chemother-apeutical and surgical treatments have achieved prom-ising results in these patients. A chance for long-term survival or even cure may now be offered to selected patients by combining radical surgical resection with intraperitoneal instillation of heated chemotherapy. This combined procedure has become known as hy-perthermic intraperitoneal chemotherapy. This edito-rial outlines recent advancements in the medical and surgical treatment of PC and reviews the most recent information on incidence and prognosis of this disease. Given recent progress, treatment should now be considered in every patient presenting with PC.展开更多
Floods are phenomenon with significant socio-economic implications mainly for human loss, agriculture, livestock, soil loss and land degradation, for which many researchers try to identify the most appropriate methodo...Floods are phenomenon with significant socio-economic implications mainly for human loss, agriculture, livestock, soil loss and land degradation, for which many researchers try to identify the most appropriate methodologies by analyzing their temporal and spatial development. This study therefore attempts to employ the GIS-based multi-criteria decision analysis and analytical hierarchy process techniques to derive the flood risks management on rice productivity in the Gishari Agricultural Marshland in Rwamagana district, Rwanda. Here, six influencing potential factors to flooding, including river slope, soil texture, Land Use Land Cover through Land Sat 8, rainfall, river distance and Digital Elevation Model are considered for the delineation of flood risk zones. Data acquisition like Landsat 8 images, DEM, land use land cover, slope, and soil class in the study area were considered. Results showed that if the DEM is outdated or inaccurate due to changes in the terrain, such as construction, excavation, or erosion, the predicted flood patterns might not reflect the actual water flow. This could result unexpected flood extents and depths, potentially inundating rice fields that were not previously at risk and this, expectedly explained that the increase 1 m in elevation would reduce the rice productivity by 0.17% due to unplanned flood risks in marshland. It was found that the change in rainfall distribution in Gishari agricultural marshland would also decrease the rice productivity by 0.0018%, which is a sign that rainfall is a major factor of flooding in rice scheme. Rainfall distribution plays a crucial role in flooding analysis and can directly impact rice productivity. Oppositely, another causal factor was Land Use Land Cover (LULC), where the Multivariate Logistic Regression Model Analysis findings showed that the increase of one unit in Land Use Land Cover would increase rice productivity by 0.17% of the total rice productivity from the Gishari Agricultural Marshland. Based on findings from these techniques展开更多
This study evaluated the genetic and agronomic parameter estimates of maize under different nitrogen rates. The trial was established at the Njala Agricultural Research Centre experimental site during 2021 and 2022 in...This study evaluated the genetic and agronomic parameter estimates of maize under different nitrogen rates. The trial was established at the Njala Agricultural Research Centre experimental site during 2021 and 2022 in a split block design with three maize varieties (IWCD2, 2009EVDT, and DMR-ESR-Yellow) and seven nitrogen (0, 30, 60, 90, 120, 150 and 180 kg∙N∙ha<sup>−</sup><sup>1</sup>) rates. Findings showed that cob diameter and anthesis silking time (ASI) had intermediate heritability, ASI had high genetic advance, ASI and grain yield had high genotypic coefficient of variation (GCV), while traits with high phenotypic coefficient of variation (PCV) were plant height, ASI, grain yield, number of kernel per cob, number of kernel rows, ear length, and ear height. The PCV values were higher than GCV, indicating the influence of the environment in the studied traits. Nitrogen rates and variety significantly (p < 0.05) influenced grain yield production. Mean grain yields and economic parameter estimates increased with increasing nitrogen rates, with the 30 and 180 kg∙N∙ha<sup>−</sup><sup>1</sup> plots exhibiting the lowest and highest grain yields of 1238 kg∙ha<sup>−</sup><sup>1</sup> and 2098 kg∙ha<sup>−</sup><sup>1</sup>, respectively. Variety and nitrogen effects on partial factor productivity (PFP<sub>N</sub>), agronomic efficiency (AEN), net returns (NR), value cost ratio (VCR) and marginal return (MR) indicated that these parameters were significantly affected (p < 0.05) by these factors. The highest PFP<sub>N</sub> (41.3 kg grain kg<sup>−</sup><sup>1</sup>∙N) and AEN (29.4 kg grain kg<sup>−</sup><sup>1</sup>∙N) were obtained in the 30 kg∙N∙ha<sup>−</sup><sup>1</sup> plots, while the highest VCR (2.8) and MR (SLL 1.8 SLL<sup>−</sup><sup>1</sup> spent on N) were obtained in the 180 kg∙N∙ha<sup>−</sup><sup>1</sup>. The significant influence of variety and nitrogen on traits suggests that increasing yields and maximizing profits require use of appropriate nitrogen fertiliz展开更多
Enterococcus faecalis and Enterococcus faecium rank among the leading causes of nosocomial bacteremia and urinary tract infections. They often persist on hospital surfaces due to their ability to withstand adverse env...Enterococcus faecalis and Enterococcus faecium rank among the leading causes of nosocomial bacteremia and urinary tract infections. They often persist on hospital surfaces due to their ability to withstand adverse environmental conditions (low or high temperatures, high pH, and high salinity). The global Enterococcus faecalis-Enterococcus faecium ratio is currently shifting towards Enterococcus faecium. Enterococci present variable levels of resistance to certain families of antibiotics. This is the case for aminoglycosides, beta-lactams and cephalosporins. In 2017, WHO ranked Enterococci among priority pathogens for research and development of new antibiotics. The objective of our study was to determine the antibiotic resistance profile of Enterococcus faecalis and Enterococcus faecium isolates from urine and pleural fluid in two hospitals in Cameroon. This cross-sectional and analytic study was carried out between June to August 2023 on hospitalized and day patients in which a cytobacteriological test of urine and pleural fluid was done. The samples were inoculated on CLED Agar for urine and on Chocolate + polyvitex and blood agar (prepared from Columbia agar) for pleural fluid samples and incubated at 37℃ for 18 to 24 hours. Identification of isolates was carried out using the API 20 STREP micro gallery (Biomerieux, France) and tested for antimicrobial susceptibility. The data on socio-demographical and potential risk factors were recorded using self-administered questionnaires and data from laboratory analyses of the specimen were collected in a data capture sheet. Potential risk factors associated with the presence of Enterococci, were evaluated using the logistic regression in univariate and multivariate analysis. P value < 0.05 was considered as significant. A total of 511 patients were recruited who were predominantly females. Enterococcus spp were isolated in 27.79% of our samples with Enterococcus faecalis mostly encountered. Enterococcus spp showed a high level of resistance to penicilline (99.3% to展开更多
Hepatocellular carcinoma(HCC)is one of the most common malignant tumors with a low survival rate.The identification of mechanisms underlying the development of HCC helps uncover cellular and mo-lecular targets for the...Hepatocellular carcinoma(HCC)is one of the most common malignant tumors with a low survival rate.The identification of mechanisms underlying the development of HCC helps uncover cellular and mo-lecular targets for the diagnosis,prevention,and treatment of HCC.Golgi protein 73(GP73)level is up-regulated in HCC patients and potentially can be a therapeutic target.Despite many studies devoted to GP73 as a marker for HCC early diagnosis,there is little discussion about the function of GP73 in HCC tumorigenesis.Given the poor response to currently available HCC therapies,a better understanding of the role of GP73 in HCC may provide a new therapeutic target for HCC.The current paper summarizes the role of GP73 as a diagnostic marker as well as its roles in liver carcinogenesis.Its roles in other types of cancer are also discussed.展开更多
Galectins(Gals)are evolutionarily conserved proteins that bind to b-galactoside containing glycans.Abnormal expression of Gals is associated with the development,progression,and metastasis of different types of cancer...Galectins(Gals)are evolutionarily conserved proteins that bind to b-galactoside containing glycans.Abnormal expression of Gals is associated with the development,progression,and metastasis of different types of cancer.Among the 11 Gals identified in humans,the roles of Gal-1 and Gal-3 have been extensively investigated in various tumors.Here,we summarize the roles of overly expressed Gal-1 and Gal-3 in the pathogenesis of hepatocellular carcinoma(HCC).The overexpression of Gal-1 and Gal-3 correlates with tumor growth,HCC cell migration and invasion,tumor aggressiveness,metastasis,and poor prognosis.A potentially promising future treatment strategy for HCC may include the combination of immunotherapy with Gal-1 inhibition.Additional research is warranted to investigate targeting Gal-1 and Gal-3 for HCC treatment.展开更多
Accumulation of macrophage"foam"cells,laden with cholesterol and cholesteryl ester,within the intima of large arteries,is a hallmark of early"fatty streak"lesions which can progress to complex,mult...Accumulation of macrophage"foam"cells,laden with cholesterol and cholesteryl ester,within the intima of large arteries,is a hallmark of early"fatty streak"lesions which can progress to complex,multicellular atheromatous plaques,involving lipoproteins from the bloodstream and cells of the innate and adaptive immune response.Sterol accumulation triggers induction of genes encoding proteins mediating the atheroprotective cholesterol efflux pathway.Within the arterial intima,however,this mechanism is overwhelmed,leading to distinct changes in macrophage phenotype and inflammatory status.Over the last decade marked gains have been made in understanding of the epigenetic landscape which influence macrophage function,and in particular the importance of small non-coding micro-RNA(miRNA)sequences in this context.This review identifies some of the miRNA sequences which play a key role in regulating"foam"cell formation and atherogenesis,highlighting sequences involved in cholesterol accumulation,those influencing inflammation in sterol-loaded cells,and novel sequences and pathways which may offer new strategies to influence macrophage function within atherosclerotic lesions.展开更多
文摘Gastric cancer is one of the leading causes of cancer mortality in the world. Aberrant expression of microRNAs (miRNAs) is the hallmark of this disease. MiRNAs are endogenous non-coding RNAs that are involved in many biological processes (e.g., cell proliferation, differentiation, apoptosis, invasion and development) through gene repression. Deregulation of miRNA expression in gastric tumors and cancer cell lines have been documented to contribute in tumorigenesis, and the expression signature may correlate with different cancer types and clinicopathological features. Here, we summarized the updated gastric cancer-associated miRNAs and the downstream targets in the process of tumorigenesis. Recently, many researchers make use of the miRNA microarray platform to profile miRNA expression in gastric cancer and correlated with different clinical parameters. Its application on cancer diagnosis, prognosis and predicting treatment response rate are still underway and needs further investigation. Emerging roles of miRNAs with oncogenic or tumor suppressive properties in gastric tumorigenesis were discussed. Epigenetic silencing of miRNA by hypermethylation of promoter CpG island was also observed in gastric cancer. However, detailed mechanisms of how miRNAs regulate gene expression in gastric cancer has not been well studied. In this review, we highlight the up-to-date findings on the deregulated miRNAs in gastric cancer, and the potential use of miRNA in the clinical settings, such as diagnostic/prognostic markers and chemotherapeutic tools.
基金supported by the National Grand Fundamental Research 973 Program of China(2007CB507406)the National NaturalScience Foundation of China(30600659)the Central and Non-profitable Basic R&D Funds for Scientific Research Institutes(IMBF200913)
文摘Objective To investigate the protective effects of putative AGEs （advanced glycation endproducts） inhibitor salidroside against aging in an accelerated mouse aging model induced by D-galactose. Methods A group of 5-month-old C57BL/6J mice were treated daily with D-galactose, D-galactose combined with salidroside, salidroside alone, and control buffer for 8 weeks. At the end of the treatment, serum AGEs levels, neurological activities, expression of glial fibrillary acidic protein （GFAP） and neurotrophin-3 （NT-3） in the cerebral cortex, as well as lymphocyte proliferation and IL-2 production were determined. Results D-galactose induced mouse aging model was developed as described before. As expected, salidroside blocked D-galactose induced increase of serum AGEs levels. It also reversed D-galactose induced aging effects in neural and immune system, as evidenced by improving motor activity, increasing memory latency time, and enhancing lymphocyte mitogenesis and interleukin-2 （IL-2） production. Furthermore, elevated expression of GFAP and NT-3 in the aged model mice was also reduced upon salidroside treatment. Conclusion Salidroside inhibits AGEs formation in vivo, which at least partially contributes to its anti-aging effect in D-galactose induced aging model.
文摘Developing realistic soil carbon （C） sequestration strategies for China＇s sustainable agriculture relies on accurate estimates of the amount, retention and turnover rates of C stored in paddy soils. Available C estimates to date are predominantly for the tilled and flood-irrigated surface topsoil （ca. 30 cm）. Such estimates cannot be used to extrapolate to soil depths of 100 cm since soil organic carbon （SOC） generally shows a sharp decrease with depth. In this research, composite soil samples were collected at several depths to 100 cm from three representative paddy soils in the Taihu Lake region, China. Soil organic carbon distribution in the profiles and in aggregate-size fractions was determined. Results showed that while SOC decreased exponentially with depth to 100 cm, a substantial proportion of the total SOC （30%-40%） is stored below the 30 cm depth. In the carbon-enriched paddy topsoils, SOC was found to accumulate preferentially in the 2-0.25 and 0.25-0.02 mm aggregate size fractions. δ^13C analysis of the coarse micro-aggregate fraction showed that the high degree of C stratification in the paddy topsoil was in agreement with the occurrence of lighter δ^1313C in the upper 30 cm depth. These results suggest that SOC stratification within profiles varies with different pedogenetical types of paddy soils with regards to clay and iron oxyhydrates distributions. Sand-sized fractions of aggregates in paddy soil systems may play a very important role in carbon sequestration and turnover, dissimilar to other studied agricultural systems.
基金Supported by Grants from the Gebert Rüf Foundation, the Forschungskredit of the University Zurichthe Swiss National Science Foundation, Grants PP00B-108511/1 and 31-64140.00
文摘AIM： To study the association of three common ABCB11 and ABCC2 polymorphisms （ABCB11： 1331T〉C→V444A; ABCC2： 3563T〉A → V1188E and 4544G 〉A → C1515Y） with intrahepatic cholestasis of pregnancy （ICP） and contraceptive-induced cholestasis （CIC）. METHODS： ABCB11 and ABCC2 genotyping data were available from four CIC patients and from 42 and 33 ICP patients, respectively. Allele-frequencies of the studied polymorphisms were compared with those in healthy pregnant controls and Caucasian individuals. Furthermore, serum bile acid levels were correlated with the presence or absence of the 1331 C allele. RESULTS： The ABCB11 1331T〉C polymorphism was significantly more frequent in cholestatic patients than in pregnant controls： C allele 76.2% （CI, 58.0-94.4） vs 51.3% （CI 35.8-66.7）, respectively （P = 0.0007）; and CC allele 57.1% （CI 36.0-78.3） vs 20% （CI 7.6-32.4）, respectively （P = 0.0065）. All four CIC patients were homozygous carriers of the C allele. In contrast, none of the studied ABCC2 polymorphism was overrepresented in ICP or CIC patients. Higher serum bile acid levels were found in carriers of the 1331CC genotype compared to carriers of the TT genotype. CONCLUSION： Our data support a role for the ABCB11 1331T〉C polymorphism as a susceptibility factor for the development of estrogen-induced cholestasis, whereas no such association was found for ABCC2. Serum bile acid and 7-glutamyl transferase levels might help to distinguish ABCB4- and ABCB11-related forms of ICP and CIC.
基金Supported by The National Clinical Key Institute Foundation of Chinese Health and Family Planning MinistryNo.2013-544
文摘AIM: To investigate Fusobacterium nucleatum (F. nucleatum) abundance in colorectal cancer (CRC) tissues and its association with CRC invasiveness in Chinese patients.METHODS: The resected cancer and adjacent normal tissues (10 cm beyond cancer margins) from 101 consecutive patients with CRC were collected. Fluorescent quantitative polymerase chain reaction (FQ-PCR) was applied to detect F. nucleatum in CRC and normal tissues. The difference of F. nucleatum abundance between cancer and normal tissues and the relationship of F. nucleatum abundance with clinical variables were evaluated. Fluorescence in situ hybridization (FISH) analysis was performed on 22 CRC tissues with the highest F. nucleatum abundance by FQ-PCR testing to confirm FQ-PCR results.RESULTS: The median abundance of F. nucleatum in CRC tissues [0.242 (0.178-0.276)] was significantly higher than that in normal controls [0.050 (0.023-0.067)] (P < 0.001). F. nucleatum was over-represented in 88/101 (87.1%) CRC samples. The abundance of F. nucleatum determined by 2<sup>-ΔCT</sup> was significantly greater in tumor samples [0.242 (0.178, 0.276)] than in normal controls [0.050 (0.023, 0.067)] (P < 0.001). The frequency of patients with lymph node metastases was higher in the over-abundance group [52/88 (59.1%)] than in the under-abundance group [0/13 (0%)] (P < 0.005). No significant association of F. nucleatum with other clinico-pathological variables was observed (P > 0.05). FISH analysis also found more F. nucleatum in CRC than in normal tissues (median number 6, 25<sup>th</sup> 3, 75<sup>th</sup> 10 vs 2, 25<sup>th</sup> 1, 75<sup>th</sup> 5) (P < 0.01).CONCLUSION: F. nucleatum was enriched in CRC tissues and associated with CRC development and metastasis.
文摘Arabidopsis MSI1 has fundamental functions in plant development. MSI1 is a subunit of Polycomb group protein complexes and Chromatin assembly factor 1, and it interacts with the Retinoblastoma-related protein 1. Altered levels of MSI1 result in pleiotropic phenotypes, reflecting the complexity of MSI1 protein functions. In order to uncover additional functions of MSI1, we performed transcriptional profiling of wild-type and plants with highly reduced MSI1 levels （msil-cs）. Surprisingly, the known functions of MSI1 could only account for a minor part of the transcriptional changes in msil-cs plants. One of the most striking unexpected observations was the up-regulation of a subset of ABA-responsive genes eliciting the response to drought and salt stress. We report that MSI1 can bind to the chromatin of the drought-inducible downstream target RD20 and suggest a new role for MSI1 in the negative regulation of the Arabidopsis drought-stress response.
文摘A severe spinal cord involvement may rarely occur in patients with cirrhosis and other chronic liver diseases;this complication is usually associated with overt liver failure and surgical or spontaneous porto-systemic shunt.Hepatic myelopathy(HM)is characterized by progressive weakness and spasticity of the lower extremities,while sensory and sphincter disturbances have rarely been described and are usually less important.The diagnosis is assigned in the appropriate clinical setting on clinical grounds after the exclusion of other clinical entities leading to spastic paraparesis.Magnetic resonance imaging is often unremarkable;however,also intracerebral corticospinal tract abnor-malities have been reported recently.The study of motor evoked potentials may disclose central conduction abnormalities even before HM is clinically manifest.HM responds poorly to blood ammonia-lowering and other conservative medical therapy.Liver transplantation represents a potentially definitive treatment for HM in patients with decompensated cirrhosis of Child-Pugh B and C grades.Other surgical treatment options in HM include surgical ligation,shunt reduction,or occlusion by interventional procedures.
文摘Liver cancer is the sixth most common cancer worldwide,and the third most common cause of cancer-related death.Hepatocellular carcinoma(HCC),which accounts for more than 90%of primary liver cancers,is an important public health problem.In addition to cirrhosis caused by hepatitis B viral(HBV)or hepatitis C viral(HCV)infection,non-alcoholic fatty liver disease(NAFLD)is becoming a major risk factor for liver cancer because of the prevalence of obesity.Non-alcoholic steatohepatitis(NASH)will likely become the leading indication for liver transplantation in the future.It is well recognized that gut microbiota is a key environmental factor in the pathogenesis of liver disease and cancer.The interplay between gut microbiota and liver disease has been investigated in animal and clinical studies.In this article,we summarize the roles of gut microbiota in the development of liver disease as well as gut microbiota-targeted therapies.
基金This study supported by grants funded by National Institutes of Health CA179582 and CA222490.
文摘Background:Probiotic VSL#3 is used to treat ulcerative colitis.This study examines the effect of VSL#3 in non-alcoholic steatohepatitis(NASH)that has liver carcinogenic potential.Methods:Western diet(WD)-fed wild-type(WT)mice that do not have hepatic inflammation with lymphocyte infiltration and carcinogenic potential were used for baseline comparison.Age-,sex-,and diet-matched bile acid(BA)receptor farnesoid X receptor(FXR)knockout(KO)mice,which developed severe NASH and had the potential for liver cancer development,were supplemented with and without VSL#3 for 7 months.All the mice were euthanized when they were 10 months old.Results:Supplementation with VSL#3 completely abolished hepatic lymphocyte infiltration,reduced hepatic fat content,and improved insulin sensitivity in WD-fed FXR KO mice.In addition,VSL#3 normalized dysregulated BA homoeostasis by inhibiting the classical BA synthesis pathway,inducing the alternative BA pathway,and activating ileal G-protein coupled BA receptor 1(GPBAR1)-regulated signaling.Moreover,VSL#3 reconstructed the gut microbiota by reducing Bacteroidaceae,Porphyromonadaceae,and Helicobacteraceae as well as increasing Lachnospiraceae.Further,VSL#3 enriched the abundance of Ruminococcus and Faecalibacterium,which generate butyrate,at the genus level.It also increased the copy number of the butyrate-producing genes bcoA and buk,suggesting their anti-inflammatory and metabolic effects.Conclusions:VSL#3 is useful in reversing NASH that occurred due to dysregulated BA synthesis and dysbiosis,suggesting its potential in liver cancer prevention.
基金This work was supported by the National Basic Research Program of China(Grant No.2017YFA0505501)Strategic Priority Research Program of the Chinese Academy of Sciences(Grant No.XDB19020201)National Natural Science Foundation of China(Grant Nos.81430066,91731314,31621003,81872312,81871875,81802279).
文摘Despite the tremendous efforts for improving therapeutics of lung cancer patients,its prognosis remains disappoint-ing.This can be largely attributed to the lack of comprehensive understanding of drug resistance leading to insuf-ficient development of effective therapeutics in clinic.Based on the current progresses of lung cancer research,we classify drug resistance mechanisms into three different levels:molecular,cellular and pathological level.All these three levels have significantly contributed to the acquisition and evolution of drug resistance in clinic.Our under-standing on drug resistance mechanisms has begun to change the way of clinical practice and improve patient prognosis.In this review,we focus on discussing the pathological changes linking to drug resistance as this has been largely overlooked in the past decades.
文摘Peritoneal carcinomatosis (PC) is one manifestation of metastatic colorectal cancer (CRC). Tumor growth on intestinal surfaces and associated fluid accumulation eventually result in bowel obstruction and incapacitating levels of ascites, which profoundly affect the quality of life for affected patients. PC appears resistant to traditional 5-fluorouracil-based chemotherapy, and surgery was formerly reserved for palliative purposes only. In the absence of effective treatment, the histori-cal prognosis for these patients was extremely poor, with an invariably fatal outcome. These poor outcomes likely explain why PC secondary to CRC has received little attention from oncologic researchers. Thus, data are lacking regarding incidence, clinical disease course, and accurate treatment evaluation for patients with PC. Recently, population-based studies have revealed that PC occurs relatively frequently among patients withCRC. Risk factors for developing PC have been identi-fied:right-sided tumor, advanced T-stage, advanced N-stage, poor differentiation grade, and younger age at diagnosis. During the past decade, both chemother-apeutical and surgical treatments have achieved prom-ising results in these patients. A chance for long-term survival or even cure may now be offered to selected patients by combining radical surgical resection with intraperitoneal instillation of heated chemotherapy. This combined procedure has become known as hy-perthermic intraperitoneal chemotherapy. This edito-rial outlines recent advancements in the medical and surgical treatment of PC and reviews the most recent information on incidence and prognosis of this disease. Given recent progress, treatment should now be considered in every patient presenting with PC.
文摘Floods are phenomenon with significant socio-economic implications mainly for human loss, agriculture, livestock, soil loss and land degradation, for which many researchers try to identify the most appropriate methodologies by analyzing their temporal and spatial development. This study therefore attempts to employ the GIS-based multi-criteria decision analysis and analytical hierarchy process techniques to derive the flood risks management on rice productivity in the Gishari Agricultural Marshland in Rwamagana district, Rwanda. Here, six influencing potential factors to flooding, including river slope, soil texture, Land Use Land Cover through Land Sat 8, rainfall, river distance and Digital Elevation Model are considered for the delineation of flood risk zones. Data acquisition like Landsat 8 images, DEM, land use land cover, slope, and soil class in the study area were considered. Results showed that if the DEM is outdated or inaccurate due to changes in the terrain, such as construction, excavation, or erosion, the predicted flood patterns might not reflect the actual water flow. This could result unexpected flood extents and depths, potentially inundating rice fields that were not previously at risk and this, expectedly explained that the increase 1 m in elevation would reduce the rice productivity by 0.17% due to unplanned flood risks in marshland. It was found that the change in rainfall distribution in Gishari agricultural marshland would also decrease the rice productivity by 0.0018%, which is a sign that rainfall is a major factor of flooding in rice scheme. Rainfall distribution plays a crucial role in flooding analysis and can directly impact rice productivity. Oppositely, another causal factor was Land Use Land Cover (LULC), where the Multivariate Logistic Regression Model Analysis findings showed that the increase of one unit in Land Use Land Cover would increase rice productivity by 0.17% of the total rice productivity from the Gishari Agricultural Marshland. Based on findings from these techniques
文摘This study evaluated the genetic and agronomic parameter estimates of maize under different nitrogen rates. The trial was established at the Njala Agricultural Research Centre experimental site during 2021 and 2022 in a split block design with three maize varieties (IWCD2, 2009EVDT, and DMR-ESR-Yellow) and seven nitrogen (0, 30, 60, 90, 120, 150 and 180 kg∙N∙ha<sup>−</sup><sup>1</sup>) rates. Findings showed that cob diameter and anthesis silking time (ASI) had intermediate heritability, ASI had high genetic advance, ASI and grain yield had high genotypic coefficient of variation (GCV), while traits with high phenotypic coefficient of variation (PCV) were plant height, ASI, grain yield, number of kernel per cob, number of kernel rows, ear length, and ear height. The PCV values were higher than GCV, indicating the influence of the environment in the studied traits. Nitrogen rates and variety significantly (p < 0.05) influenced grain yield production. Mean grain yields and economic parameter estimates increased with increasing nitrogen rates, with the 30 and 180 kg∙N∙ha<sup>−</sup><sup>1</sup> plots exhibiting the lowest and highest grain yields of 1238 kg∙ha<sup>−</sup><sup>1</sup> and 2098 kg∙ha<sup>−</sup><sup>1</sup>, respectively. Variety and nitrogen effects on partial factor productivity (PFP<sub>N</sub>), agronomic efficiency (AEN), net returns (NR), value cost ratio (VCR) and marginal return (MR) indicated that these parameters were significantly affected (p < 0.05) by these factors. The highest PFP<sub>N</sub> (41.3 kg grain kg<sup>−</sup><sup>1</sup>∙N) and AEN (29.4 kg grain kg<sup>−</sup><sup>1</sup>∙N) were obtained in the 30 kg∙N∙ha<sup>−</sup><sup>1</sup> plots, while the highest VCR (2.8) and MR (SLL 1.8 SLL<sup>−</sup><sup>1</sup> spent on N) were obtained in the 180 kg∙N∙ha<sup>−</sup><sup>1</sup>. The significant influence of variety and nitrogen on traits suggests that increasing yields and maximizing profits require use of appropriate nitrogen fertiliz
文摘Enterococcus faecalis and Enterococcus faecium rank among the leading causes of nosocomial bacteremia and urinary tract infections. They often persist on hospital surfaces due to their ability to withstand adverse environmental conditions (low or high temperatures, high pH, and high salinity). The global Enterococcus faecalis-Enterococcus faecium ratio is currently shifting towards Enterococcus faecium. Enterococci present variable levels of resistance to certain families of antibiotics. This is the case for aminoglycosides, beta-lactams and cephalosporins. In 2017, WHO ranked Enterococci among priority pathogens for research and development of new antibiotics. The objective of our study was to determine the antibiotic resistance profile of Enterococcus faecalis and Enterococcus faecium isolates from urine and pleural fluid in two hospitals in Cameroon. This cross-sectional and analytic study was carried out between June to August 2023 on hospitalized and day patients in which a cytobacteriological test of urine and pleural fluid was done. The samples were inoculated on CLED Agar for urine and on Chocolate + polyvitex and blood agar (prepared from Columbia agar) for pleural fluid samples and incubated at 37℃ for 18 to 24 hours. Identification of isolates was carried out using the API 20 STREP micro gallery (Biomerieux, France) and tested for antimicrobial susceptibility. The data on socio-demographical and potential risk factors were recorded using self-administered questionnaires and data from laboratory analyses of the specimen were collected in a data capture sheet. Potential risk factors associated with the presence of Enterococci, were evaluated using the logistic regression in univariate and multivariate analysis. P value < 0.05 was considered as significant. A total of 511 patients were recruited who were predominantly females. Enterococcus spp were isolated in 27.79% of our samples with Enterococcus faecalis mostly encountered. Enterococcus spp showed a high level of resistance to penicilline (99.3% to
基金This study was supported bygrants funded by the USA National Institutes of Health(NIH)R01CA222490 to Y.-J.Y.Wanalong with grants from the National Natural Science Foundation of China Project number 81602456financial sup-port from the China Scholarship Council(CSC)to Y.Wang.
文摘Hepatocellular carcinoma(HCC)is one of the most common malignant tumors with a low survival rate.The identification of mechanisms underlying the development of HCC helps uncover cellular and mo-lecular targets for the diagnosis,prevention,and treatment of HCC.Golgi protein 73(GP73)level is up-regulated in HCC patients and potentially can be a therapeutic target.Despite many studies devoted to GP73 as a marker for HCC early diagnosis,there is little discussion about the function of GP73 in HCC tumorigenesis.Given the poor response to currently available HCC therapies,a better understanding of the role of GP73 in HCC may provide a new therapeutic target for HCC.The current paper summarizes the role of GP73 as a diagnostic marker as well as its roles in liver carcinogenesis.Its roles in other types of cancer are also discussed.
基金This manuscript is supported by grants funded by the USA National Institutes of Health(NIH)U01CA179582,R01CA222490,T32 CA108459-15UC Davis Comprehensive Cancer Center seed grant.
文摘Galectins(Gals)are evolutionarily conserved proteins that bind to b-galactoside containing glycans.Abnormal expression of Gals is associated with the development,progression,and metastasis of different types of cancer.Among the 11 Gals identified in humans,the roles of Gal-1 and Gal-3 have been extensively investigated in various tumors.Here,we summarize the roles of overly expressed Gal-1 and Gal-3 in the pathogenesis of hepatocellular carcinoma(HCC).The overexpression of Gal-1 and Gal-3 correlates with tumor growth,HCC cell migration and invasion,tumor aggressiveness,metastasis,and poor prognosis.A potentially promising future treatment strategy for HCC may include the combination of immunotherapy with Gal-1 inhibition.Additional research is warranted to investigate targeting Gal-1 and Gal-3 for HCC treatment.
文摘Accumulation of macrophage"foam"cells,laden with cholesterol and cholesteryl ester,within the intima of large arteries,is a hallmark of early"fatty streak"lesions which can progress to complex,multicellular atheromatous plaques,involving lipoproteins from the bloodstream and cells of the innate and adaptive immune response.Sterol accumulation triggers induction of genes encoding proteins mediating the atheroprotective cholesterol efflux pathway.Within the arterial intima,however,this mechanism is overwhelmed,leading to distinct changes in macrophage phenotype and inflammatory status.Over the last decade marked gains have been made in understanding of the epigenetic landscape which influence macrophage function,and in particular the importance of small non-coding micro-RNA(miRNA)sequences in this context.This review identifies some of the miRNA sequences which play a key role in regulating"foam"cell formation and atherogenesis,highlighting sequences involved in cholesterol accumulation,those influencing inflammation in sterol-loaded cells,and novel sequences and pathways which may offer new strategies to influence macrophage function within atherosclerotic lesions.
