Gastric ulcer(GU)represents a clinically significant manifestation of peptic ulcer disease,driven by a complex interplay of microbial,environmental,and immuneinflammatory factors.A recent cross-sectional study by Shen...Gastric ulcer(GU)represents a clinically significant manifestation of peptic ulcer disease,driven by a complex interplay of microbial,environmental,and immuneinflammatory factors.A recent cross-sectional study by Shen et al systematically evaluated six complete blood count-derived inflammatory indices:Neutrophil-tolymphocyte ratio,monocyte-to-lymphocyte ratio,platelet-to-lymphocyte ratio,systemic immune-inflammation index,systemic inflammatory response index(SIRI),and aggregate index of systemic inflammation and demonstrated their positive associations with GU prevalence,identifying SIRI as the strongest predictor.This editorial contextualizes these findings within the broader literature,clarifies that these indices reflect systemic rather than GU-specific inflammation,highlights methodological strengths and major limitations,and proposes a conceptual clinical algorithm for integrating SIRI into GU risk assessment.Future multicenter studies incorporating Helicobacter pylori infection,non-steroidal antiinflammatory drug exposure,and prospective design are essential to validate and translate these findings into clinical practice.展开更多
The improvements of high-throughput experimental devices such as microarray and mass spectrometry have allowed an effective acquisition of biological comprehensive data which include genome, transcriptome, proteome, a...The improvements of high-throughput experimental devices such as microarray and mass spectrometry have allowed an effective acquisition of biological comprehensive data which include genome, transcriptome, proteome, and metabolome (multi-layered omics data). In Systems Biology, we try to elucidate various dynamical characteristics of biological functions with applying the omics data to detailed mathematical model based on the central dogma. However, such mathematical models possess multi-time-scale properties which are often accompanied by time-scale differences seen among biological layers. The differences cause time stiff problem, and have a grave influence on numerical calculation stability. In the present conventional method, the time stiff problem remained because the calculation of all layers was implemented by adaptive time step sizes of the smallest time-scale layer to ensure stability and maintain calculation accuracy. In this paper, we designed and developed an effective numerical calculation method to improve the time stiff problem. This method consisted of ahead, backward, and cumulative algorithms. Both ahead and cumulative algorithms enhanced calculation efficiency of numerical calculations via adjustments of step sizes of each layer, and reduced the number of numerical calculations required for multi-time-scale models with the time stiff problem. Backward algorithm ensured calculation accuracy in the multi-time-scale models. In case studies which were focused on three layers system with 60 times difference in time-scale order in between layers, a proposed method had almost the same calculation accuracy compared with the conventional method in spite of a reduction of the total amount of the number of numerical calculations. Accordingly, the proposed method is useful in a numerical analysis of multi-time-scale models with time stiff problem.展开更多
Traditional Chinese medicine(TCM)has shown remarkable potential for treating liver fibrosis.In this study,to identify novel TCMs with antifibrotic properties,we used a technique called high-throughput sequencing-based...Traditional Chinese medicine(TCM)has shown remarkable potential for treating liver fibrosis.In this study,to identify novel TCMs with antifibrotic properties,we used a technique called high-throughput sequencing-based high-throughput screening(HTS2),which is based on RNA-mediated oligonucleotide annealing,selection,and ligation followed by sequencing.This technology achieved parallel and quantitative analysis of gene expression in response to thousands of drug treatments[1].展开更多
Hematologic malignancies,including leukemia,lymphoma,and multiple myeloma,are hazardous diseases characterized by the uncontrolled proliferation of cancer cells.Dysregulated cell cycle resulting from genetic and epige...Hematologic malignancies,including leukemia,lymphoma,and multiple myeloma,are hazardous diseases characterized by the uncontrolled proliferation of cancer cells.Dysregulated cell cycle resulting from genetic and epigenetic abnormalities constitutes one of the central events.Importantly,cyclin-dependent kinases(CDKs),complexed with their functional partner cyclins,play dominating roles in cell cycle control.Yet,efforts in translating CDK inhibitors into clinical benefits have demonstrated disappointing outcomes.Recently,mounting evidence highlights the emerging significance of WEE1 G2 checkpoint kinase(WEE1)to modulate CDK activity,and correspondingly,a variety of therapeutic inhibitors have been developed to achieve clinical benefits.Thus,WEE1 may become a promising target to modulate the abnormal cell cycle.However,its function in hematologic diseases remains poorly elucidated.In this review,focusing on hematologic malignancies,we describe the biological structure of WEE1,emphasize the latest reported function of WEE1 in the carcinogenesis,progression,as well as prognosis,and finally summarize the therapeutic strategies by targeting WEE1.展开更多
Non-alcoholic fatty liver disease(NAFLD),a critical global health concern,continues to challenge medical researchers with limited treatment options.This letter examines on the study by Luo et al,demonstrating that vit...Non-alcoholic fatty liver disease(NAFLD),a critical global health concern,continues to challenge medical researchers with limited treatment options.This letter examines on the study by Luo et al,demonstrating that vitamin D 1,25-dihydroxyvitamin D3[1,25(OH)2D3]improves hepatic steatosis in NAFLD by inhibiting M1 macrophage polarization via the vitamin D receptor-peroxisome proliferator-activated receptor gamma signaling pathway.This letter critically appraises these findings,comparing them to similar studies,and discusses their potential implications for treating NAFLD.Furthermore,we highlight future directions,including dose optimization and mechanistic studies.展开更多
Cancer treatment often requires a multimodal approach,such as combining chemotherapy and gene therapy.However,challenges such as low therapeutic efficacy and off-target effects hinder the effectiveness of these treatm...Cancer treatment often requires a multimodal approach,such as combining chemotherapy and gene therapy.However,challenges such as low therapeutic efficacy and off-target effects hinder the effectiveness of these treatments.In this study,the use of calcium-doped metal-organic frameworks Cu_(2)(BDC)_(2)(DABCO)as a nanocarrier platform for the co-delivery of doxorubicin(DOX)and plasmid CRISPR(pCRISPR)proposed to enhance anticancer efficiency.We demonstrated that Ca-doped MOF nanocarriers significantly improved the uptake of DOX and pCRISPR by in cancer cells.The co-delivery of DOX and pCRISPR with Ca-doped MOF nanocarriers resulted in a significant rise in cell death and decreased targeted gene expression.展开更多
Amplification-free,highly sensitive,and specific nucleic acid detection is crucial for health monitoring and diagnosis.The type III CRISPR-Cas10 system,which provides viral immunity through CRISPRassociated protein ef...Amplification-free,highly sensitive,and specific nucleic acid detection is crucial for health monitoring and diagnosis.The type III CRISPR-Cas10 system,which provides viral immunity through CRISPRassociated protein effectors,enables a new amplification-free nucleic acid diagnostic tool.In this study,we develop a CRISPR-graphene field-effect transistors(GFETs)biosensor by combining the type III CRISPR-Cas10 system with GFETs for direct nucleic acid detection.This biosensor exploits the target RNA-activated continuous ss DNA cleavage activity of the d Csm3 CRISPR-Cas10 effector and the high charge density of a hairpin DNA reporter on the GFET channel to achieve label-free,amplification-free,highly sensitive,and specific RNA detection.The CRISPR-GFET biosensor exhibits excellent performance in detecting medium-length RNAs and miRNAs,with detection limits at the aM level and a broad linear range of 10^(-15)to 10^(-11)M for RNAs and 10^(-15)to 10^(-9)M for miRNAs.It shows high sensitivity in throat swabs and serum samples,distinguishing between healthy individuals(N=5)and breast cancer patients(N=6)without the need for extraction,purification,or amplification.This platform mitigates risks associated with nucleic acid amplification and cross-contamination,making it a versatile and scalable diagnostic tool for molecular diagnostics in human health.展开更多
This article comments on the study by Peng et al,published in the World Journal of Gastrointestinal Surgery,representing a notable advancement in hepatobiliary surgery.This article examines laparoscopic anatomical seg...This article comments on the study by Peng et al,published in the World Journal of Gastrointestinal Surgery,representing a notable advancement in hepatobiliary surgery.This article examines laparoscopic anatomical segment VIII resection,a challenging procedure due to the complex liver anatomy and difficulty in accessing deep-seated lesions.Peng and colleagues’experience with caudal and cranial approaches in 34 patients underscores the feasibility of these techniques while sparking debates about the optimal approach.Their study’s strengths lie in technique standardization and comprehensive analysis,although its limitations highlight the need for further research.As minimally invasive liver surgery progresses,larger,prospective trials and integration of advanced technologies are essential for establishing best practices.展开更多
Lactylation,a newly identified post-translational modification,plays a multifaceted role in cancer biology by integrating epigenetic and non-epigenetic mechanisms.This review summarizes the latest research progress on...Lactylation,a newly identified post-translational modification,plays a multifaceted role in cancer biology by integrating epigenetic and non-epigenetic mechanisms.This review summarizes the latest research progress on lactylation,including its functions in epigenetic regulation and its broader impact on cellular processes.Lactate,as a metabolic byproduct,not only serves as an energy source for tumor cells but also acts as a signaling molecule driving various oncogenic processes.Lactylation facilitates cancer metabolic reprogramming,enabling tumor cells to adapt to hypoxic and nutrient-deprivedmicroenvironments.Moreover,lactylationmediates immune suppression in the tumormicroenvironment,promoting immune evasion and therapy resistance.This review further explores the clinical potential of targeting lactylation,offering new avenues for innovation in cancer research and treatment.These findings highlight the pivotal role of lactylation in cancer progression and its significant value as a potential therapeutic target.展开更多
Cancer,a leading cause of global mortality,remains a significant challenge to increasing life expectancy worldwide.Forkhead Box R2(FOXR2),identified as an oncogene within the FOX gene family,plays a crucial role in de...Cancer,a leading cause of global mortality,remains a significant challenge to increasing life expectancy worldwide.Forkhead Box R2(FOXR2),identified as an oncogene within the FOX gene family,plays a crucial role in developing various endoderm-derived organs.Recent studies have elucidated FOXR2-related pathways and their involvement in both tumor and non-tumor diseases.Dysregulation of FOXR2 has been linked to numerous malignant tumors,spanning the brain,nervous system,thyroid,osteosarcoma,Hodgkin lymphoma,colorectal,liver,pancreatic,lung,breast,ovarian,prostate,female genital tract,endometrial,and uterine cancers.Despite extensive research on FOXR2 dysregulation,its practical applications remain underexplored.This review delves into the mechanisms underlying FOXR2 dysregulation during oncogenesis and its implications for cancer diagnosis,prognosis,and treatment.展开更多
Immunoglobulin E(IgE)is a critical biomarker for diagnosing allergic and other immune diseases.However,traditional IgE detection methods are often time-consuming and require specialized operation.As an important bioma...Immunoglobulin E(IgE)is a critical biomarker for diagnosing allergic and other immune diseases.However,traditional IgE detection methods are often time-consuming and require specialized operation.As an important biomarker,researchers have used different strategies and explored various materials for designing IgE biosensors with highly sensitivity,specificity and cost-effectiveness.In this review,we comprehensively summarize recent advances in biosensing technologies for IgE detection,categorizing them into optical,electrochemical,and piezoelectric biosensors.It elaborates on the design principles,performance metrics,and comparative advantages of various platforms,such as surface plasmon resonance(SPR),fluorescence,electrochemical impedance spectroscopy(EIS),and quartz crystal microbalance(QCM).The integration of novel materials like aptamers and nanomaterials has significantly enhanced the performance of these biosensors.Biosensors present a promising alternative for rapid,sensitive,and efficient IgE detection,holding great potential for future clinical diagnostics and point-of-care testing applications.Future perspectives should highlight the discovery of novel materials,the application of artificial intelligence for aptamer development,and the synergy of optoelectronic sensing strategies to improve analytical performance for clinical diagnostics.展开更多
Chemotherapy is the preferred therapeutic approach for advanced ovarian cancer,but a successful long-term treatment is prevented by the development of drug resistance.Recent works have underlined the involvement of no...Chemotherapy is the preferred therapeutic approach for advanced ovarian cancer,but a successful long-term treatment is prevented by the development of drug resistance.Recent works have underlined the involvement of non-coding RNAs,microRNAs（miRNAs） in cancer development,with several conjectures regarding their possible involvement in the evolution of drug resistance.This study is to investigate the promoting effects and mechanism of miR-125b involved in the development of chemoresistance in ovarian cancer.The different expression of miR-125b in cisplatin-sensitive ovarian cancer cell line（OV2008） and its resistant variant（C13＊） was identified by real-time PCR.An in vitro cytotoxicity assay and apoptosis assay using CCK-8 assay and flow cytometry,were carried out to detect the effect of miR-125b and Bak1 on cisplatin resistance of cells.Real-time PCR,Western blotting and luciferase reporter assay were used to detect whether Bak1 is a target of miR-125b.As compared with OV2008 cells,the expression levels of miR-125b in C13＊ cells were increased.It was found that the up-regulation of microRNA-125b caused a marked inhibition of cisplatin-induced cytotoxicity and apoptosis and a subsequent increase in the resistance to cisplatin in OV2008 and C13＊ cells.Moreover,Bak1 was a direct target of miR-125b,and down-regulation of Bak1 suppressed cisplatin-induced apoptosis and led to an increased resistance to cisplatin.Our study indicates that miR-125b has a significantly promoting effect on chemoresistance of C13＊ cells and up-regulation of miR-125b expression contributes to cisplatin resistance through suppression of Bak1 expression.This finding has important implications in the development of targeted therapeutics for overcoming cisplatin resistance in ovarian cancer.展开更多
Objective: To check biofilm formation by Acinetobacter baumannii(A. baumannii)clinical isolates and show their susceptibility to different antibiotics and investigate a possible link between establishment of biofilm a...Objective: To check biofilm formation by Acinetobacter baumannii(A. baumannii)clinical isolates and show their susceptibility to different antibiotics and investigate a possible link between establishment of biofilm and multidrug resistance.Methods: This study was performed on clinical samples collected from patients with nosocomial infections in three hospitals of Tehran. Samples were initially screened by culture and biochemical tests for the presence of different species of Acinetobacter. Identifications were further confirmed by PCR assays. Their susceptibilities to 11 antibiotics of different classes were determined by disc diffusion method according to Clinical and Laboratory Standards Institute guidelines. The ability to produce biofilm was investigated using methods: culture on Congo red agar, microtiter plate, and test tube method.Results: From the overall clinical samples, 156 specimens were confirmed to contain A. baumannii. The bacteria were highly resistant to most antibiotics except polymyxin B.Of these isolates, 10.26% were able to produce biofilms as shown on Congo red agar.However, the percentage of bacteria with positive biofilm in test tube, standard microtiter plate, and modified microtiter plate assays were 48.72%, 66.66%, and 73.72%, respectively. At least 92% of the biofilm forming isolates were multidrug resistant.Conclusions: Since most of the multidrug resistant strains produce biofilm, it seems necessary to provide continuous monitoring and determination of antibiotic susceptibility of clinical A. baumannii. This would help to select the most appropriate antibiotic for treatment.展开更多
INTRODUCTIONThe point mutation rate of k-ras gene at codon 12 inpancreatic adenocarcinoma is reported to be as highas 90%,and with no mutations in normalpancreas tissues or other pancreatic disorders.Wehave detected t...INTRODUCTIONThe point mutation rate of k-ras gene at codon 12 inpancreatic adenocarcinoma is reported to be as highas 90%,and with no mutations in normalpancreas tissues or other pancreatic disorders.Wehave detected the presence of k-ras gene展开更多
Rice(Oryza sativa L.)is an important staple food crop worldwide due to its adaptability to different environmental conditions.Because of its great economic and social importance,there is a constant requirement for new...Rice(Oryza sativa L.)is an important staple food crop worldwide due to its adaptability to different environmental conditions.Because of its great economic and social importance,there is a constant requirement for new varieties with improved agronomic characteristics,such as tolerance to different biotic(such as bacterium,fungus,insect and virus)and abiotic stresses(such as salinity,drought and temperature),higher yield and better organoleptic and nutritional value.Among the new genome editing technologies,the clustered regularly interspaced short palindromic repeats(CRISPR)/CRISPR-associated protein(Cas)(CRISPR/Cas)system allows precise and specific edition in a targeted genome region.It is one of the most frequently used techniques for the study of the function of new genes and for the development of mutant lines with enhanced tolerance to biotic and abiotic stresses,herbicide resistance or improved yield.The wide varieties of applications for this technology include simple non-homologous end joining,homologous recombination,gene replacement,and base editing.In this review,we analyzed how some of these applications have been used in rice cultivars to obtain rice varieties better adapted to current environmental conditions and market requirements.展开更多
Objective:To design a duplex PCR for rapid and simultaneous detection of Brucella species, in human blood samples.Methods:Fifty-two peripheral bloods samples were collected from suspicious patients with brucellosis.Fo...Objective:To design a duplex PCR for rapid and simultaneous detection of Brucella species, in human blood samples.Methods:Fifty-two peripheral bloods samples were collected from suspicious patients with brucellosis.Following DNA extraction,PCR assay were performed, using three primers that could simultaneously identify and differentiate three major species of pathogenic Brucella in humans and animals.Results:Of the 52 peripheral bloods samples tested, 25 sample(48%) showed positive reactions in PCR.Twelve samples were positive for Brucella abortus(B.abortus)(23%,13 for Brucella melUensis(B.melUensis)(25%) and 0 for Brucella ovis (6.ovis)(Ow.Conclusions:This work de=monstrates dial in case where specific primers were utilized,duplex PCR has proved to be a simple,fast,and relatively inexpensive method for simultaneous detection of important species of Brucella in clinical samples.展开更多
The aim of the present study was to examine the effects of suppression of EphB4 and/or mTOR on the biological behaviors of ovarian cancer cells, and the potential regulatory pathways. An-tisense EphB4 vectors and shRN...The aim of the present study was to examine the effects of suppression of EphB4 and/or mTOR on the biological behaviors of ovarian cancer cells, and the potential regulatory pathways. An-tisense EphB4 vectors and shRNA vectors targeting mammalian target of rapamycin （mTOR） were constructed and transfected into A2780 and SKOV3 cells （two ovarian cancer cell lines）. The effects of the antisense EphB4 vectors and the shRNA vectors on the proliferation, apoptosis and invasion of ovarian cancer cells were measured, and the expression of EphB4, mTOR and Akt detected. The results showed that transfection with mTOR shRNA could inhibit growth, induce apoptosis, and reduce invasive ability of ovarian cancer cells, which was accompanied by downregulation of EphB4, mTOR and Akt. The inhibitory effects on cell growth caused by mTOR shRNA alone were weaker than those by antisense pEGFP-C1-EphB4. In the antisense pEGFP-C1-EphB4-transfected cells, it was found that EphB4 knockdown could decrease the mTOR expression and slightly reduce the Akt phosphorylation. Significant suppressive effects on cell growth were observed in cells co-transfected with antisense pEGFP-C1-EphB4 and mTOR shRNA. In co-transfection group, the expression levels of EphB4, mTOR and Akt were distinctly lower than those in other groups. It was concluded that suppression of EphB4 may inhibit the growth of ovarian cancer cells by downregulation of the PI3K/Akt/mTOR pathway, and reverse Akt phosphorylation induced by mTOR shRNA. Inhibition of EphB4 and mTOR combined may cooperatively suppress the biological behaviors of ovarian cancer cells.展开更多
Objective:To investigate antibiotic resistance and carriage class 1 and 2 integrons in clinical isolates of Acinetobacter baumannii(A.baumannii)from Tehran,Iran.Methods:Antimicrobial susceptibility testing was perform...Objective:To investigate antibiotic resistance and carriage class 1 and 2 integrons in clinical isolates of Acinetobacter baumannii(A.baumannii)from Tehran,Iran.Methods:Antimicrobial susceptibility testing was performed according to the Clinical and Laboratory Standards Institute.The presence of integrons was investigated by PCR using specific primers.Results:Among isolated A.baumannii strains,82%were multidrug resistant,27 samples(54%)were resistant to three or more than three antibiotics and 16 samples(32%)showed resistance to two antibiotics.Integrons were detected from 44 of 50 isolates(88%),with classes 1 and 2 being observed in 42%(21/50)and 82%(41/50)of isolates,respectively.Integron-positive A.baumannii isolates showed higher antibiotic resistance than integron-negative isolates and all showed a multidrug-resistant phenotype.Conclusions:Our findings show that classes 1 and 2 integrons,and especially classes 2 integrons are widely disseminated among A.baumannii strains isolated from Tehran and these structures are playing a major role in the acquisition of multidrug resistance in these strains.So monitoring of drug resistance with investigating carriage class 1 and 2 integrons is very important to plan specific infection control measures due to multidrug resistance A.baumannii in Iran hospitals.展开更多
AIM： To investigate the effect of tetramethylpyrazine （TMP）, an active compound from Ligustium Wollichii Franchat, on electrolyte transport across the distal colon of rodents and the mechanism involved.METHODS： Th...AIM： To investigate the effect of tetramethylpyrazine （TMP）, an active compound from Ligustium Wollichii Franchat, on electrolyte transport across the distal colon of rodents and the mechanism involved.METHODS： The short-circuit current （Isc） technique in conjunction with pharmacological agents and specific inhibitors were used in analyzing the electrolyte transport across the distal colon of rodents. The underlying cellular signaling mechanism was investigated by radioimmunoassay analysis （RIA） and a special mouse model of cystic fibrosis.RESULTS： IMP stimulated a conoentration-dependent rise in ISCl, which was dependent on both Cl^- and HCO3^-, and inhibited by apical application of diphenylamine-2,2＇-dicarboxylic acid （DPC） and glibenclamide, but resistant to 4,4＇-diisothiocyanatostilbene-2,2＇-disulfonic acid disodium salt hydrate （DIDS）. Removal of Na^＋ from basolateral solution almost completely abolished the Isc response to TMP, but it was insensitive to apical Na^＋ replacement or apical Na^＋ channel blocker, amiloride. Pretreatment of colonic mucosa with BAPTA-AM, a membrane-permeable selective Ca2＋ chelator, did not significantly alter the TMP-induced Iso No additive effect of forskolin and 3-isobutyl-l-methylxanthine （[BMX） was observed on the TMP-induced Isc, but it was significantly reduced by a protein kinase A inhibitor, H89.RIA results showed that TMP （1 mmol/L） elicited a significant increase in cellular cAMP production, which was similar to that elicited by the adenylate cyclase activator, forskolin （10μmol/L）. The TMP-elicited Isc as well as forskolin- or IBMX-induced Isc were abolished in mice with homozygous mutation of the cystic fibrosis transmembrane conductance regulator （CFTR） presenting defective CFTR functions and secretions.CONCLUSION： TMP may stimulate cAMP-dependent and CFTR-mediated Cl^- and HCO3^- secretion. This may have implications in the future development of alternative treatment for constipation.展开更多
Prior to fertilization sperm has to undergo an activation process known as capaciation,leading to the acrosome reaction.Till now,little is known about the mechanism for preventing premature capacitation in sperm altho...Prior to fertilization sperm has to undergo an activation process known as capaciation,leading to the acrosome reaction.Till now,little is known about the mechanism for preventing premature capacitation in sperm although decapacitation factors from various sources have been thought to be involved.In this study,we report that NYD-SP27,an isoform of phospholipase C Zeta 1(PLCZ1),is localized to the sperm acrosome in mouse and human spermatozoa by immunofluorescence using a specific antibody.Western blot and double staining analyses show NYD-SP27 becomes detached from sperm,as they undergo capacitation and acrosome reaction.The absence of HCO_(3)^(-),a key factor in activating capacitation,from the capacitation-inducing medium prevents the loss of NYD-SP27 from sperm.The anti-NYD-SP27 antibody also prevents the loss of NYD-SP27 from sperm,reduced the number of capacitated sperm,inhibited the acrosome reaction induced by ATP and progesterone,and inhibited agonist-induced PLC-coupled Ca^(2+)mobilization in sperm,which can be mimicked by the PLC inhibitor,U73122.These data strongly suggest that NYD-SP27 is a physiological inhibitor of PLC that acts as an intrinsic decapacitation factor in sperm to prevent premature capacitation and acrosome reaction.展开更多
基金Supported by the National Natural Science Foundation of China,No.82170406 and No.81970238.
文摘Gastric ulcer(GU)represents a clinically significant manifestation of peptic ulcer disease,driven by a complex interplay of microbial,environmental,and immuneinflammatory factors.A recent cross-sectional study by Shen et al systematically evaluated six complete blood count-derived inflammatory indices:Neutrophil-tolymphocyte ratio,monocyte-to-lymphocyte ratio,platelet-to-lymphocyte ratio,systemic immune-inflammation index,systemic inflammatory response index(SIRI),and aggregate index of systemic inflammation and demonstrated their positive associations with GU prevalence,identifying SIRI as the strongest predictor.This editorial contextualizes these findings within the broader literature,clarifies that these indices reflect systemic rather than GU-specific inflammation,highlights methodological strengths and major limitations,and proposes a conceptual clinical algorithm for integrating SIRI into GU risk assessment.Future multicenter studies incorporating Helicobacter pylori infection,non-steroidal antiinflammatory drug exposure,and prospective design are essential to validate and translate these findings into clinical practice.
文摘The improvements of high-throughput experimental devices such as microarray and mass spectrometry have allowed an effective acquisition of biological comprehensive data which include genome, transcriptome, proteome, and metabolome (multi-layered omics data). In Systems Biology, we try to elucidate various dynamical characteristics of biological functions with applying the omics data to detailed mathematical model based on the central dogma. However, such mathematical models possess multi-time-scale properties which are often accompanied by time-scale differences seen among biological layers. The differences cause time stiff problem, and have a grave influence on numerical calculation stability. In the present conventional method, the time stiff problem remained because the calculation of all layers was implemented by adaptive time step sizes of the smallest time-scale layer to ensure stability and maintain calculation accuracy. In this paper, we designed and developed an effective numerical calculation method to improve the time stiff problem. This method consisted of ahead, backward, and cumulative algorithms. Both ahead and cumulative algorithms enhanced calculation efficiency of numerical calculations via adjustments of step sizes of each layer, and reduced the number of numerical calculations required for multi-time-scale models with the time stiff problem. Backward algorithm ensured calculation accuracy in the multi-time-scale models. In case studies which were focused on three layers system with 60 times difference in time-scale order in between layers, a proposed method had almost the same calculation accuracy compared with the conventional method in spite of a reduction of the total amount of the number of numerical calculations. Accordingly, the proposed method is useful in a numerical analysis of multi-time-scale models with time stiff problem.
文摘Traditional Chinese medicine(TCM)has shown remarkable potential for treating liver fibrosis.In this study,to identify novel TCMs with antifibrotic properties,we used a technique called high-throughput sequencing-based high-throughput screening(HTS2),which is based on RNA-mediated oligonucleotide annealing,selection,and ligation followed by sequencing.This technology achieved parallel and quantitative analysis of gene expression in response to thousands of drug treatments[1].
基金supported by grants from the National Natural Science Foundation of China(No.81920108004,82270127,82203880)the Hunan Provincial Natural Science Foundation of China(No.2023JJ30928,2024JJ3037)+2 种基金the Changsha Municipal Natural Sci-Science Foundation(No.kq2208382)the Fellowship of the China Postdoctoral Science Foundation(No.2023T160740)the Hunan Province Clinical Medical Technology Innovation Guidance Project(No.2021SK50917,2023SK4056)。
文摘Hematologic malignancies,including leukemia,lymphoma,and multiple myeloma,are hazardous diseases characterized by the uncontrolled proliferation of cancer cells.Dysregulated cell cycle resulting from genetic and epigenetic abnormalities constitutes one of the central events.Importantly,cyclin-dependent kinases(CDKs),complexed with their functional partner cyclins,play dominating roles in cell cycle control.Yet,efforts in translating CDK inhibitors into clinical benefits have demonstrated disappointing outcomes.Recently,mounting evidence highlights the emerging significance of WEE1 G2 checkpoint kinase(WEE1)to modulate CDK activity,and correspondingly,a variety of therapeutic inhibitors have been developed to achieve clinical benefits.Thus,WEE1 may become a promising target to modulate the abnormal cell cycle.However,its function in hematologic diseases remains poorly elucidated.In this review,focusing on hematologic malignancies,we describe the biological structure of WEE1,emphasize the latest reported function of WEE1 in the carcinogenesis,progression,as well as prognosis,and finally summarize the therapeutic strategies by targeting WEE1.
基金National Natural Science Foundation of China,No.82170406 and No.81970238.
文摘Non-alcoholic fatty liver disease(NAFLD),a critical global health concern,continues to challenge medical researchers with limited treatment options.This letter examines on the study by Luo et al,demonstrating that vitamin D 1,25-dihydroxyvitamin D3[1,25(OH)2D3]improves hepatic steatosis in NAFLD by inhibiting M1 macrophage polarization via the vitamin D receptor-peroxisome proliferator-activated receptor gamma signaling pathway.This letter critically appraises these findings,comparing them to similar studies,and discusses their potential implications for treating NAFLD.Furthermore,we highlight future directions,including dose optimization and mechanistic studies.
文摘Cancer treatment often requires a multimodal approach,such as combining chemotherapy and gene therapy.However,challenges such as low therapeutic efficacy and off-target effects hinder the effectiveness of these treatments.In this study,the use of calcium-doped metal-organic frameworks Cu_(2)(BDC)_(2)(DABCO)as a nanocarrier platform for the co-delivery of doxorubicin(DOX)and plasmid CRISPR(pCRISPR)proposed to enhance anticancer efficiency.We demonstrated that Ca-doped MOF nanocarriers significantly improved the uptake of DOX and pCRISPR by in cancer cells.The co-delivery of DOX and pCRISPR with Ca-doped MOF nanocarriers resulted in a significant rise in cell death and decreased targeted gene expression.
基金financially supported by the National Science and Technology Innovation 2030 Grants(2021ZD0201600)the National Key R&D Program of China(2021YFA0717000)+2 种基金the Intramural Joint Program Fund of State Key Laboratory of Microbial Technology(Project No.SKLMTIJP-2024-05)the Natural Science Foundation of Qingdao-Original exploration project(Project No.24-4-4-zrjj-139-jch)the National Natural Science Foundation of China(31771380)。
文摘Amplification-free,highly sensitive,and specific nucleic acid detection is crucial for health monitoring and diagnosis.The type III CRISPR-Cas10 system,which provides viral immunity through CRISPRassociated protein effectors,enables a new amplification-free nucleic acid diagnostic tool.In this study,we develop a CRISPR-graphene field-effect transistors(GFETs)biosensor by combining the type III CRISPR-Cas10 system with GFETs for direct nucleic acid detection.This biosensor exploits the target RNA-activated continuous ss DNA cleavage activity of the d Csm3 CRISPR-Cas10 effector and the high charge density of a hairpin DNA reporter on the GFET channel to achieve label-free,amplification-free,highly sensitive,and specific RNA detection.The CRISPR-GFET biosensor exhibits excellent performance in detecting medium-length RNAs and miRNAs,with detection limits at the aM level and a broad linear range of 10^(-15)to 10^(-11)M for RNAs and 10^(-15)to 10^(-9)M for miRNAs.It shows high sensitivity in throat swabs and serum samples,distinguishing between healthy individuals(N=5)and breast cancer patients(N=6)without the need for extraction,purification,or amplification.This platform mitigates risks associated with nucleic acid amplification and cross-contamination,making it a versatile and scalable diagnostic tool for molecular diagnostics in human health.
基金Supported by National Natural Science Foundation of China,No.82170406 and No.81970238.
文摘This article comments on the study by Peng et al,published in the World Journal of Gastrointestinal Surgery,representing a notable advancement in hepatobiliary surgery.This article examines laparoscopic anatomical segment VIII resection,a challenging procedure due to the complex liver anatomy and difficulty in accessing deep-seated lesions.Peng and colleagues’experience with caudal and cranial approaches in 34 patients underscores the feasibility of these techniques while sparking debates about the optimal approach.Their study’s strengths lie in technique standardization and comprehensive analysis,although its limitations highlight the need for further research.As minimally invasive liver surgery progresses,larger,prospective trials and integration of advanced technologies are essential for establishing best practices.
基金National Natural Science Foundation of China,Grant/Award Numbers:82372672,81974414,82403469the National key research and development program,Grant/Award Number:2024YFC2707400+1 种基金Project of the Central Government Guiding Local in Shanxi Province,Grant/Award Number:YDZJSX2022B012Research and Innovation Team Project for Scientific Breakthroughs at Shanxi Bethune Hospital,Grant/Award Number:2024ZHANCHI08。
文摘Lactylation,a newly identified post-translational modification,plays a multifaceted role in cancer biology by integrating epigenetic and non-epigenetic mechanisms.This review summarizes the latest research progress on lactylation,including its functions in epigenetic regulation and its broader impact on cellular processes.Lactate,as a metabolic byproduct,not only serves as an energy source for tumor cells but also acts as a signaling molecule driving various oncogenic processes.Lactylation facilitates cancer metabolic reprogramming,enabling tumor cells to adapt to hypoxic and nutrient-deprivedmicroenvironments.Moreover,lactylationmediates immune suppression in the tumormicroenvironment,promoting immune evasion and therapy resistance.This review further explores the clinical potential of targeting lactylation,offering new avenues for innovation in cancer research and treatment.These findings highlight the pivotal role of lactylation in cancer progression and its significant value as a potential therapeutic target.
文摘Cancer,a leading cause of global mortality,remains a significant challenge to increasing life expectancy worldwide.Forkhead Box R2(FOXR2),identified as an oncogene within the FOX gene family,plays a crucial role in developing various endoderm-derived organs.Recent studies have elucidated FOXR2-related pathways and their involvement in both tumor and non-tumor diseases.Dysregulation of FOXR2 has been linked to numerous malignant tumors,spanning the brain,nervous system,thyroid,osteosarcoma,Hodgkin lymphoma,colorectal,liver,pancreatic,lung,breast,ovarian,prostate,female genital tract,endometrial,and uterine cancers.Despite extensive research on FOXR2 dysregulation,its practical applications remain underexplored.This review delves into the mechanisms underlying FOXR2 dysregulation during oncogenesis and its implications for cancer diagnosis,prognosis,and treatment.
文摘Immunoglobulin E(IgE)is a critical biomarker for diagnosing allergic and other immune diseases.However,traditional IgE detection methods are often time-consuming and require specialized operation.As an important biomarker,researchers have used different strategies and explored various materials for designing IgE biosensors with highly sensitivity,specificity and cost-effectiveness.In this review,we comprehensively summarize recent advances in biosensing technologies for IgE detection,categorizing them into optical,electrochemical,and piezoelectric biosensors.It elaborates on the design principles,performance metrics,and comparative advantages of various platforms,such as surface plasmon resonance(SPR),fluorescence,electrochemical impedance spectroscopy(EIS),and quartz crystal microbalance(QCM).The integration of novel materials like aptamers and nanomaterials has significantly enhanced the performance of these biosensors.Biosensors present a promising alternative for rapid,sensitive,and efficient IgE detection,holding great potential for future clinical diagnostics and point-of-care testing applications.Future perspectives should highlight the discovery of novel materials,the application of artificial intelligence for aptamer development,and the synergy of optoelectronic sensing strategies to improve analytical performance for clinical diagnostics.
基金supported by grants from the National Natural Sciences Foundation of China (No.81001153)the "973" Program of China (No. 2009CB521808)
文摘Chemotherapy is the preferred therapeutic approach for advanced ovarian cancer,but a successful long-term treatment is prevented by the development of drug resistance.Recent works have underlined the involvement of non-coding RNAs,microRNAs（miRNAs） in cancer development,with several conjectures regarding their possible involvement in the evolution of drug resistance.This study is to investigate the promoting effects and mechanism of miR-125b involved in the development of chemoresistance in ovarian cancer.The different expression of miR-125b in cisplatin-sensitive ovarian cancer cell line（OV2008） and its resistant variant（C13＊） was identified by real-time PCR.An in vitro cytotoxicity assay and apoptosis assay using CCK-8 assay and flow cytometry,were carried out to detect the effect of miR-125b and Bak1 on cisplatin resistance of cells.Real-time PCR,Western blotting and luciferase reporter assay were used to detect whether Bak1 is a target of miR-125b.As compared with OV2008 cells,the expression levels of miR-125b in C13＊ cells were increased.It was found that the up-regulation of microRNA-125b caused a marked inhibition of cisplatin-induced cytotoxicity and apoptosis and a subsequent increase in the resistance to cisplatin in OV2008 and C13＊ cells.Moreover,Bak1 was a direct target of miR-125b,and down-regulation of Bak1 suppressed cisplatin-induced apoptosis and led to an increased resistance to cisplatin.Our study indicates that miR-125b has a significantly promoting effect on chemoresistance of C13＊ cells and up-regulation of miR-125b expression contributes to cisplatin resistance through suppression of Bak1 expression.This finding has important implications in the development of targeted therapeutics for overcoming cisplatin resistance in ovarian cancer.
基金Supported by an educational grant for doctoral thesis from Islamic Azad University of Karaj(grant number:11530554922001)
文摘Objective: To check biofilm formation by Acinetobacter baumannii(A. baumannii)clinical isolates and show their susceptibility to different antibiotics and investigate a possible link between establishment of biofilm and multidrug resistance.Methods: This study was performed on clinical samples collected from patients with nosocomial infections in three hospitals of Tehran. Samples were initially screened by culture and biochemical tests for the presence of different species of Acinetobacter. Identifications were further confirmed by PCR assays. Their susceptibilities to 11 antibiotics of different classes were determined by disc diffusion method according to Clinical and Laboratory Standards Institute guidelines. The ability to produce biofilm was investigated using methods: culture on Congo red agar, microtiter plate, and test tube method.Results: From the overall clinical samples, 156 specimens were confirmed to contain A. baumannii. The bacteria were highly resistant to most antibiotics except polymyxin B.Of these isolates, 10.26% were able to produce biofilms as shown on Congo red agar.However, the percentage of bacteria with positive biofilm in test tube, standard microtiter plate, and modified microtiter plate assays were 48.72%, 66.66%, and 73.72%, respectively. At least 92% of the biofilm forming isolates were multidrug resistant.Conclusions: Since most of the multidrug resistant strains produce biofilm, it seems necessary to provide continuous monitoring and determination of antibiotic susceptibility of clinical A. baumannii. This would help to select the most appropriate antibiotic for treatment.
基金Natural Science Foundation of Jiangsu Scientific Committee
文摘INTRODUCTIONThe point mutation rate of k-ras gene at codon 12 inpancreatic adenocarcinoma is reported to be as highas 90%,and with no mutations in normalpancreas tissues or other pancreatic disorders.Wehave detected the presence of k-ras gene
文摘Rice(Oryza sativa L.)is an important staple food crop worldwide due to its adaptability to different environmental conditions.Because of its great economic and social importance,there is a constant requirement for new varieties with improved agronomic characteristics,such as tolerance to different biotic(such as bacterium,fungus,insect and virus)and abiotic stresses(such as salinity,drought and temperature),higher yield and better organoleptic and nutritional value.Among the new genome editing technologies,the clustered regularly interspaced short palindromic repeats(CRISPR)/CRISPR-associated protein(Cas)(CRISPR/Cas)system allows precise and specific edition in a targeted genome region.It is one of the most frequently used techniques for the study of the function of new genes and for the development of mutant lines with enhanced tolerance to biotic and abiotic stresses,herbicide resistance or improved yield.The wide varieties of applications for this technology include simple non-homologous end joining,homologous recombination,gene replacement,and base editing.In this review,we analyzed how some of these applications have been used in rice cultivars to obtain rice varieties better adapted to current environmental conditions and market requirements.
基金supported by Molecular Biology Research Center, Baqiyatallah University of Medical Sciences,with grant number BMSU/MBRC-90-001
文摘Objective:To design a duplex PCR for rapid and simultaneous detection of Brucella species, in human blood samples.Methods:Fifty-two peripheral bloods samples were collected from suspicious patients with brucellosis.Following DNA extraction,PCR assay were performed, using three primers that could simultaneously identify and differentiate three major species of pathogenic Brucella in humans and animals.Results:Of the 52 peripheral bloods samples tested, 25 sample(48%) showed positive reactions in PCR.Twelve samples were positive for Brucella abortus(B.abortus)(23%,13 for Brucella melUensis(B.melUensis)(25%) and 0 for Brucella ovis (6.ovis)(Ow.Conclusions:This work de=monstrates dial in case where specific primers were utilized,duplex PCR has proved to be a simple,fast,and relatively inexpensive method for simultaneous detection of important species of Brucella in clinical samples.
基金supported by grants from the National Natural Science Foundation of China(No.81001006)the"973"Program of China(No.2009CB521800)the Specialized Research Fund for the Doctoral Program of Higher Education of China(No.200804871030)
文摘The aim of the present study was to examine the effects of suppression of EphB4 and/or mTOR on the biological behaviors of ovarian cancer cells, and the potential regulatory pathways. An-tisense EphB4 vectors and shRNA vectors targeting mammalian target of rapamycin （mTOR） were constructed and transfected into A2780 and SKOV3 cells （two ovarian cancer cell lines）. The effects of the antisense EphB4 vectors and the shRNA vectors on the proliferation, apoptosis and invasion of ovarian cancer cells were measured, and the expression of EphB4, mTOR and Akt detected. The results showed that transfection with mTOR shRNA could inhibit growth, induce apoptosis, and reduce invasive ability of ovarian cancer cells, which was accompanied by downregulation of EphB4, mTOR and Akt. The inhibitory effects on cell growth caused by mTOR shRNA alone were weaker than those by antisense pEGFP-C1-EphB4. In the antisense pEGFP-C1-EphB4-transfected cells, it was found that EphB4 knockdown could decrease the mTOR expression and slightly reduce the Akt phosphorylation. Significant suppressive effects on cell growth were observed in cells co-transfected with antisense pEGFP-C1-EphB4 and mTOR shRNA. In co-transfection group, the expression levels of EphB4, mTOR and Akt were distinctly lower than those in other groups. It was concluded that suppression of EphB4 may inhibit the growth of ovarian cancer cells by downregulation of the PI3K/Akt/mTOR pathway, and reverse Akt phosphorylation induced by mTOR shRNA. Inhibition of EphB4 and mTOR combined may cooperatively suppress the biological behaviors of ovarian cancer cells.
基金supported by Cell and Molecular Biology Research Center and Microbiology group of Tehran Medicine University,with grant number TUMS/CMBRC-89-007
文摘Objective:To investigate antibiotic resistance and carriage class 1 and 2 integrons in clinical isolates of Acinetobacter baumannii(A.baumannii)from Tehran,Iran.Methods:Antimicrobial susceptibility testing was performed according to the Clinical and Laboratory Standards Institute.The presence of integrons was investigated by PCR using specific primers.Results:Among isolated A.baumannii strains,82%were multidrug resistant,27 samples(54%)were resistant to three or more than three antibiotics and 16 samples(32%)showed resistance to two antibiotics.Integrons were detected from 44 of 50 isolates(88%),with classes 1 and 2 being observed in 42%(21/50)and 82%(41/50)of isolates,respectively.Integron-positive A.baumannii isolates showed higher antibiotic resistance than integron-negative isolates and all showed a multidrug-resistant phenotype.Conclusions:Our findings show that classes 1 and 2 integrons,and especially classes 2 integrons are widely disseminated among A.baumannii strains isolated from Tehran and these structures are playing a major role in the acquisition of multidrug resistance in these strains.So monitoring of drug resistance with investigating carriage class 1 and 2 integrons is very important to plan specific infection control measures due to multidrug resistance A.baumannii in Iran hospitals.
基金Supported by the Innovation and Technology Fund of Hong Kong, China
文摘AIM： To investigate the effect of tetramethylpyrazine （TMP）, an active compound from Ligustium Wollichii Franchat, on electrolyte transport across the distal colon of rodents and the mechanism involved.METHODS： The short-circuit current （Isc） technique in conjunction with pharmacological agents and specific inhibitors were used in analyzing the electrolyte transport across the distal colon of rodents. The underlying cellular signaling mechanism was investigated by radioimmunoassay analysis （RIA） and a special mouse model of cystic fibrosis.RESULTS： IMP stimulated a conoentration-dependent rise in ISCl, which was dependent on both Cl^- and HCO3^-, and inhibited by apical application of diphenylamine-2,2＇-dicarboxylic acid （DPC） and glibenclamide, but resistant to 4,4＇-diisothiocyanatostilbene-2,2＇-disulfonic acid disodium salt hydrate （DIDS）. Removal of Na^＋ from basolateral solution almost completely abolished the Isc response to TMP, but it was insensitive to apical Na^＋ replacement or apical Na^＋ channel blocker, amiloride. Pretreatment of colonic mucosa with BAPTA-AM, a membrane-permeable selective Ca2＋ chelator, did not significantly alter the TMP-induced Iso No additive effect of forskolin and 3-isobutyl-l-methylxanthine （[BMX） was observed on the TMP-induced Isc, but it was significantly reduced by a protein kinase A inhibitor, H89.RIA results showed that TMP （1 mmol/L） elicited a significant increase in cellular cAMP production, which was similar to that elicited by the adenylate cyclase activator, forskolin （10μmol/L）. The TMP-elicited Isc as well as forskolin- or IBMX-induced Isc were abolished in mice with homozygous mutation of the cystic fibrosis transmembrane conductance regulator （CFTR） presenting defective CFTR functions and secretions.CONCLUSION： TMP may stimulate cAMP-dependent and CFTR-mediated Cl^- and HCO3^- secretion. This may have implications in the future development of alternative treatment for constipation.
基金National 973 Project of China(No.2006CB504002),Chinese National Prominent Youth Foundation(No.30425006)Program for Changjiang Scholars and Innovative Research Team in University(PCSIRT)(No.IRT0631)+1 种基金Research Grants Council(RGC)of Hong Kong(No.CUHK4524/05M)Li Ka Shing Institute of Health Sciences and Focused Investment of the Chinese University of Hong Kong,China.
文摘Prior to fertilization sperm has to undergo an activation process known as capaciation,leading to the acrosome reaction.Till now,little is known about the mechanism for preventing premature capacitation in sperm although decapacitation factors from various sources have been thought to be involved.In this study,we report that NYD-SP27,an isoform of phospholipase C Zeta 1(PLCZ1),is localized to the sperm acrosome in mouse and human spermatozoa by immunofluorescence using a specific antibody.Western blot and double staining analyses show NYD-SP27 becomes detached from sperm,as they undergo capacitation and acrosome reaction.The absence of HCO_(3)^(-),a key factor in activating capacitation,from the capacitation-inducing medium prevents the loss of NYD-SP27 from sperm.The anti-NYD-SP27 antibody also prevents the loss of NYD-SP27 from sperm,reduced the number of capacitated sperm,inhibited the acrosome reaction induced by ATP and progesterone,and inhibited agonist-induced PLC-coupled Ca^(2+)mobilization in sperm,which can be mimicked by the PLC inhibitor,U73122.These data strongly suggest that NYD-SP27 is a physiological inhibitor of PLC that acts as an intrinsic decapacitation factor in sperm to prevent premature capacitation and acrosome reaction.
