Hepatitis B virus(HBV)infection,although preventable by vaccination,remains a global health problem and a major cause of chronic liver disease.Although current treatment strategies suppress viral replication very effi...Hepatitis B virus(HBV)infection,although preventable by vaccination,remains a global health problem and a major cause of chronic liver disease.Although current treatment strategies suppress viral replication very efficiently,the optimal endpoint of hepatitis B surface antigen(HBsAg)clearance is rarely achieved.Moreover,the thorny problems of persistent chromatin-like covalently closed circular DNA and the presence of integrated HBV DNA in the host genome are ignored.Therefore,the scientific community has focused on developing innovative therapeutic approaches to achieve a functional cure of HBV,defined as undetectable HBV DNA and HBsAg loss over a limited treatment period.A deeper understanding of the HBV life cycle has led to the introduction of novel direct-acting antivirals that exert their function through multiple mechanisms,including inhibition of viral entry,transcriptional silencing,epigenetic manipulation,interference with capsid assembly,and disruption of HBsAg release.In parallel,another category of new drugs aims to restore dysregulated immune function in chronic hepatitis B accompanied by lethargic cellular and humoral responses.Stimulation of innate immunity by pattern-recognition receptor agonists leads to upregulation of antiviral cytokine expression and appears to contribute to HBV containment.Immune checkpoint inhibitors and adoptive transfer of genetically engineered T cells are breakthrough technologies currently being explored that may elicit potent HBV-specific T-cell responses.In addition,several clinical trials are attempting to clarify the role of therapeutic vaccination in this setting.Ultimately,it is increasingly recognized that elimination of HBV requires a treatment regimen based on a combination of multiple drugs.This review describes the rationale for progressive therapeutic interventions and discusses the latest findings in the field of HBV therapeutics.展开更多
BACKGROUND Multiple myeloma(MM)is a terminal differentiated B-cell tumor disease characterized by clonal proliferation of malignant plasma cells and excessive levels of monoclonal immunoglobulins in the bone marrow.Th...BACKGROUND Multiple myeloma(MM)is a terminal differentiated B-cell tumor disease characterized by clonal proliferation of malignant plasma cells and excessive levels of monoclonal immunoglobulins in the bone marrow.The translocation,(t)(4;14),results in high-risk MM with limited treatment alternatives.Thus,there is an urgent need for identification and validation of potential treatments for this MM subtype.Microarray data and sequencing information from public databases could offer opportunities for the discovery of new diagnostic or therapeutic targets.AIM To elucidate the molecular basis and search for potential effective drugs of t(4;14)MM subtype by employing a comprehensive approach.METHODS The transcriptional signature of t(4;14)MM was sourced from the Gene Expression Omnibus.Two datasets,GSE16558 and GSE116294,which included 17 and 15 t(4;14)MM bone marrow samples,and five and four normal bone marrow samples,respectively.After the differentially expressed genes were identified,the Cytohubba tool was used to screen for hub genes.Then,the hub genes were analyzed using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis.Using the STRING database and Cytoscape,protein–protein interaction networks and core targets were identified.Potential small-molecule drugs were identified and validated using the Connectivity Map database and molecular docking analysis,respectively.RESULTS In this study,a total of 258 differentially expressed genes with enriched functions in cancer pathways,namely cytokine receptor interactions,nuclear factor(NF)-κB signaling pathway,lipid metabolism,atherosclerosis,and Hippo signaling pathway,were identified.Ten hub genes(cd45,vcam1,ccl3,cd56,app,cd48,btk,ccr2,cybb,and cxcl12)were identified.Nine drugs,including ivermectin,deforolimus,and isoliquiritigenin,were predicted by the Connectivity Map database to have potential therapeutic effects on t(4;14)MM.In molecular docking,ivermectin showed strong binding affinity to all 10 identified targets,especially cd45 and cybb.Ivermectin inhibited t(4;14)MM cell growth via the NF-κB pathway and induced MM cell apoptosis in vitro.Furthermore,ivermectin increased reactive oxygen species accumulation and altered the mitochondrial membrane potential in t(4;14)MM cells.CONCLUSION Collectively,the findings offer valuable molecular insights for biomarker validation and potential drug development in t(4;14)MM diagnosis and treatment,with ivermectin emerging as a potential therapeutic alternative.展开更多
Diabetic retinopathy (DR), a major micro-vascular complication of diabetes, has emerged as a leading cause of visual impairment and blindness among working adults in the worldwide. The pathobiology of DR involves mult...Diabetic retinopathy (DR), a major micro-vascular complication of diabetes, has emerged as a leading cause of visual impairment and blindness among working adults in the worldwide. The pathobiology of DR involves multiple molecular pathways and is characterized chronic neurovascular degeneration. Current approaches to prevent or to treat DR are still far from satisfactory. Therefore, it is important to develop new therapeutic strategies for the prevention and treatment to DR. Pigment epithelium-derived factor (PEDF), a 50-kDa secreted glycoprotein, has been described as a multi-functional protein. Some emerging evidences indicate that PEDF are able to target multiple pathways exerting neurotropic, neuroprotective, anti-angiogenic, antivasopermeability, anti-inflammation, anti-thrombogenic and anti-oxidative effects in DR. In this review, we addressed the functions of PEDF in different pathways, which could lead to potential therapeutics on the treatment to DR.展开更多
Therapeutic monoclonal antibodies have become one of the central components of the healthcare system and continuous efforts are made to bring innovative antibody therapeutics to patients in need.It is equally critical...Therapeutic monoclonal antibodies have become one of the central components of the healthcare system and continuous efforts are made to bring innovative antibody therapeutics to patients in need.It is equally critical to acquire sufficient knowledge of their molecular structure and biological functions to ensure the efficacy and safety by incorporating new detection approaches since new challenges like individual differences and resistance are presented.Conventional techniques for determining antibody disposition including plasma drug concentration measurements using LC-MS or ELISA,and tissue distribution using immunohistochemistry and immunofluorescence are now complemented with molecular imaging modalities like positron emission tomography and near-infrared fluorescence imaging to obtain more dynamic information,while methods for characterization of antibody’s interaction with the target antigen as well as visualization of its cellular and intercellular behavior are still under development.Recent progress in detecting therapeutic antibodies,in particular,the development of methods suitable for illustrating the molecular dynamics,is described here.展开更多
Gastric cancer(GC)is the fourth leading cause of cancer-related death.The occurrence and development of GC is a complex process involving multiple biological mechanisms.Although traditional regulation modulates molecu...Gastric cancer(GC)is the fourth leading cause of cancer-related death.The occurrence and development of GC is a complex process involving multiple biological mechanisms.Although traditional regulation modulates molecular functions related to the occurrence and development of GC,the comprehensive mechanisms remain unclear.Ultraconserved region(UCR)refers to a genome sequence that is completely conserved in the homologous regions of the human,rat and mouse genomes,with 100%identity,without any insertions or deletions,and often located in fragile sites and tumour-related genes.The transcribed UCR(T-UCR)is transcribed from the UCR and is a new type of long noncoding RNA.Recent studies have found that the expression level of T-UCRs changes during the occurrence and development of GC,revealing a new mechanism underlying GC.Therefore,this article aims to review the relevant research on T-UCRs in GC,as well as the function of T-UCRs and their regulatory role in the occurrence and development of GC,to provide new strategies for GC diagnosis and treatment.展开更多
The cytokine channel’s mechanism for self-regulation involves the application of antagonistic cytokines that are synthesized to connect to the receptors and release soluble cytokine receptors.The very first receptor ...The cytokine channel’s mechanism for self-regulation involves the application of antagonistic cytokines that are synthesized to connect to the receptors and release soluble cytokine receptors.The very first receptor antagonist of cytokine that was naturally present was interleukin-1 receptor antagonist(IL-1Ra).The IL-1Ra protein forms are disinfected from supernatants of cultured monocytes on stacked IgG.The family of IL-1 consists of IL-1α,IL-1βand IL-1Ra.Human monocytes regulate the production of IL-Ra.IL-Ra takes part in normal physiological functions by using specific antibodies,and acts as an anti-inflammatory agent.IL-Ra is synthesized in the tissues during the period of active disease and can be systematically measured and/or estimated.Maintenance of the levels of IL-Ra and IL-1 is the main factor for host resistance in patients during diseased conditions,as IL-Ra acts as an inherent regulator of various inflammatory responses.In this article,we focuse on how IL-Ra is synthesized and performs its functions once the inflammatory responses are activated.展开更多
B-cell CLL/lymphoma 9(BCL9)is considered a key developmental regulator and a well-established oncogenic driver in multiple cancer types,mainly through potentiating the Wnt/β-catenin signaling.However,increasing evide...B-cell CLL/lymphoma 9(BCL9)is considered a key developmental regulator and a well-established oncogenic driver in multiple cancer types,mainly through potentiating the Wnt/β-catenin signaling.However,increasing evidences indicate that BCL9 also plays multiple Wnt-independent roles.Herein,we summarized the updates of the canonical and non-canonical functions of BCL9 in cellular,physiological,or pathological processes.Moreover,we also concluded that the targeted inhibitors disrupt the interaction ofβ-catenin with BCL9 reported recently.展开更多
Background:Non‐small cell lung cancer(NSCLC),including the lung squamous cell carcinoma(LUSC)and lung adenocarcinoma(LUAD)subtypes,is a malignant tumor type with a poor 5‐year survival rate.The identification of new...Background:Non‐small cell lung cancer(NSCLC),including the lung squamous cell carcinoma(LUSC)and lung adenocarcinoma(LUAD)subtypes,is a malignant tumor type with a poor 5‐year survival rate.The identification of new powerful diagnostic biomarkers,prognostic biomarkers,and potential therapeutic targets in NSCLC is urgently required.Methods:The UCSC Xena,UALCAN,and GEO databases were used to screen and analyze differentially expressed genes,regulatory modes,and genetic/epigenetic alterations in NSCLC.The UCSC Xena database,GEO database,tissue microarray,and immunohistochemistry staining analyses were used to evaluate the diagnostic and prognostic values.Gain‐of‐function assays were performed to examine the roles.The ESTIMATE,TIMER,Linked Omics,STRING,and DAVID algorithms were used to analyze potential molecular mechanisms.Results:NR3C2 was identified as a potentially important molecule in NSCLC.NR3C2 is expressed at low levels in NSCLC,LUAD,and LUSC tissues,which is significantly related to the clinical indexes of these patients.Receiver operating characteristic curve analysis suggests that the altered NR3C2 expression patterns have diagnostic value in NSCLC,LUAD,and especially LUSC patients.Decreased NR3C2 expression levels can help predict poor prognosis in NSCLC and LUAD patients but not in LUSC patients.These results have been confirmed both with database analysis and real‐world clinical samples on a tissue microarray.Copy number variation contributes to low NR3C2 expression levels in NSCLC and LUAD,while promoter DNA methylation is involved in its downregulation in LUSC.Two NR3C2 promoter methylation sites have high sensitivity and specificity for LUSC diagnosis with clinical application potential.NR3C2 may be a key participant in NSCLC development and progression and is closely associated with the tumor microenvironment and immune cell infiltration.NR3C2 co‐expressed genes are involved in many cancer‐related signaling pathways,further supporting a potentially significant role of NR3C2 in NSCLC.Conclusions:NR3C2 is a novel potential diagnostic and prognostic biomarker and therapeutic target in NSCLC.展开更多
AIM:To investigate effects of perirenal space blocking(PSB)on gastrointestinal function in patients with severe acute pancreatitis(SAP).METHODS:Forty patients with SAP were randomly allocated to receive PSB or no PSB(...AIM:To investigate effects of perirenal space blocking(PSB)on gastrointestinal function in patients with severe acute pancreatitis(SAP).METHODS:Forty patients with SAP were randomly allocated to receive PSB or no PSB(NPSB).All the SAP patients received specialized medical therapy(SMT).Patients in the PSB group received PSB+SMT when hospitalized and after diagnosis,whereas patients in the NPSB group only received SMT.A modifed gastrointestinal failure(GIF)scoring system was used to assess the gastrointestinal function in SAP patients after admission.Pain severity(visual analog scale,0 to100)was monitored every 24 h for 72 h.RESULTS:Modified GIF score decreased in both groups during the 10-d study period.The median score decrease was initially significantly greater in the PSB group than in the NPSB group after PSB was per-formed.During the 72-h study period,pain intensity decreased in both groups.The median pain decrease was significantly greater in the PSB group than in the NPSB group at single time points.Patients in the PSB group had significantly lower incidences of hospital mortality,multiple organ dysfunction syndrome,systemic inflammatory response syndrome,and pancreatic infection,and stayed in the intensive care unit for a shorter duration.However,no difference in terms of operation incidence was found between the two groups.CONCLUSION:PSB could ameliorate gastrointestinal dysfunction or failure during the early stage of SAP.Moreover,PSB administration could improve prognosis and decrease the mortality of SAP patients.展开更多
Objective To study the damage of liver function after transcatheter arterial chemoembolization (TACE) with low-dose versus conventional-dose anticancer drugs in patients with hepatocellular carcinoma (HCC). Methods On...Objective To study the damage of liver function after transcatheter arterial chemoembolization (TACE) with low-dose versus conventional-dose anticancer drugs in patients with hepatocellular carcinoma (HCC). Methods One hundred and twelve patients with unresectable HCC were randomly divided into two groups (A and B) to receive superselective TACE. Low-dose anticancer drugs including mitomycin C (MMC) 2 ～ 8 mg,epirubicin (EPI) 5 ～ 10 mg and carboplatin (CBP) 100 mg were used in group A (n = 52),and conventional-dose of anticancer drugs (MMC 10 mg,EPI 40 mg and CBP 300 mg)for patients in group B(n = 60). Lipiodol-anticancer drugs emulsion was injected into the feeding arteries of tumor and then followed by embolization of gelatin sponge (GS) or polyvinyl alcohol (PVA) particles. Laboratory examination of the liver function including Child-Pugh scores,total bilirubin (TBIL),albumin (ALB) and alanine aminotransferase (ALT) were evaluated respectively before TACE and at third day,one week and four weeks after this procedure. Results In both groups,TBIL,ALT,and Child-Pugh scores increased (P < 0.001 or P < 0.05) and ALB decreased (P < 0.001 or P < 0.01) at three days and one week after TACE. Four weeks after-procedure,all the parameters described above showed no significant difference than those before the procedure in group A (P > 0.05). On the contrary in group B,a significant difference (P < 0.05) was found in the comparison of these parameters (except ALT). Conclusion Superselective TACE with low-dose anticancer drugs may induce transient impairment of liver function in the patients with HCC,but those patients used conventional-dose of anticancer drugs frequently cause lasting and more serious worsening of liver function. (J Intervent Radiol,2006,15: 351-355)展开更多
BACKGROUND Acute myelitis(AM)can lead to sudden sensory,motor and autonomic nervous dysfunction,which negatively affects their daily activities and quality of life,so it is necessary to explore optimization from a the...BACKGROUND Acute myelitis(AM)can lead to sudden sensory,motor and autonomic nervous dysfunction,which negatively affects their daily activities and quality of life,so it is necessary to explore optimization from a therapeutic perspective to curb the progression of the disease.AIM To investigate the effect of ganglioside(GM)combined with methylprednisolone sodium succinate(MPSS)on the curative effect and neurological function of patients with AM.METHODS First,we selected 108 AM patients visited between September 2019 and September 2022 and grouped them based on treatment modality,with 52 patients receiving gamma globulin(GG)+MPSS and 56 patients receiving GM+MPSS,assigned to the control group(Con)and observation group(Obs),respectively.The therapeutic effect,neurological function(sensory and motor function scores),adverse events(AEs),recovery(time to sphincter function recovery,time to limb muscle strength recovery above grade 2,and time to ambulation),inflammatory factors(IFs)[interleukin(IL)-6,C-reactive protein(CRP),and tumor necrosis factor(TNF)-α]and other data of the two groups were collected for evaluation and comparison.RESULTS The Obs had:(1)A significantly higher response rate of treatment than the Con;(2)Higher scores of sensory and motor functions after treatment that were higher than the baseline(before treatment)and higher than the Con levels;(3)Lower incidence rates of skin rash,gastrointestinal discomfort,dyslipidemia,osteoporosis and other AEs;(4)Faster posttreatment recovery of sphincter function,limb muscle strength and ambulation;and(5)Markedly lower posttreatment IL-6,CRP and TNF-αlevels than the baseline and the Con levels.CONCLUSION From the above,it can be seen that GM+MPSS is highly effective in treating AM,with a favorable safety profile comparable to that of GG+MPSS.It can significantly improve patients’neurological function,speed up their recovery and inhibit serum IFs.展开更多
We have previously found that long-term effects of exposure to radiofrequency electromagnetic fields in 5xFAD mice with severe late-stage Alzheimer’s disease reduced both amyloid-βdeposition and glial activation,inc...We have previously found that long-term effects of exposure to radiofrequency electromagnetic fields in 5xFAD mice with severe late-stage Alzheimer’s disease reduced both amyloid-βdeposition and glial activation,including microglia.To examine whether this therapeutic effect is due to the regulation of activated microglia,we analyzed mic roglial gene expression profiles and the existence of microglia in the brain in this study.5xFAD mice at the age of 1.5 months were assigned to sham-and radiofrequency electromagnetic fields-exposed groups and then animals were exposed to 1950 MHz radiofrequency electromagnetic fields at a specific absorption rate of 5 W/kg for 2 hours/day and 5 days/week for 6 months.We conducted behavioral tests including the object recognition and Y-maze tests and molecular and histopathological analysis of amyloid precursor protein/a myloid-beta metabolism in brain tissue.We confirmed that radiofrequency electromagnetic field exposure for 6 months ameliorated cognitive impairment and amyloid-βdeposition.The expression levels of Iba1(pan-microglial marker)and colony-stimulating factor 1 receptor(CSF1R;regulates microglial prolife ration)in the hippocampus in 5xFAD mice treated with radiofrequency electromagnetic fields were significantly reduced compared with those of the sham-exposed group.Subsequently,we analyzed the expression levels of genes related to mic rogliosis and microglial function in the radiofrequency electromagnetic fields-exposed group compared to those of a CSF1R inhibitor(PLX3397)-treated group.Both radiofrequency electromagnetic fields and PLX3397 suppressed the levels of genes related to microgliosis(Csf1r,CD68,and Ccl6)and pro-inflammatory cytokine interleukin-1β.N otably,the expression levels of genes related to mic roglial function,including Trem2,Fcgr1α,Ctss,and Spi1,were decreased after long-term radiofrequency electromagnetic field exposure,which was also observed in response to microglial suppression by PLX3397.These results showed that radiofrequency electromagnetic fields ameliorated amyloid-βpathology and cognitive impairment by suppressing amyloid-βdeposition-induced microgliosis and their key regulator,CSF1R.展开更多
文摘Hepatitis B virus(HBV)infection,although preventable by vaccination,remains a global health problem and a major cause of chronic liver disease.Although current treatment strategies suppress viral replication very efficiently,the optimal endpoint of hepatitis B surface antigen(HBsAg)clearance is rarely achieved.Moreover,the thorny problems of persistent chromatin-like covalently closed circular DNA and the presence of integrated HBV DNA in the host genome are ignored.Therefore,the scientific community has focused on developing innovative therapeutic approaches to achieve a functional cure of HBV,defined as undetectable HBV DNA and HBsAg loss over a limited treatment period.A deeper understanding of the HBV life cycle has led to the introduction of novel direct-acting antivirals that exert their function through multiple mechanisms,including inhibition of viral entry,transcriptional silencing,epigenetic manipulation,interference with capsid assembly,and disruption of HBsAg release.In parallel,another category of new drugs aims to restore dysregulated immune function in chronic hepatitis B accompanied by lethargic cellular and humoral responses.Stimulation of innate immunity by pattern-recognition receptor agonists leads to upregulation of antiviral cytokine expression and appears to contribute to HBV containment.Immune checkpoint inhibitors and adoptive transfer of genetically engineered T cells are breakthrough technologies currently being explored that may elicit potent HBV-specific T-cell responses.In addition,several clinical trials are attempting to clarify the role of therapeutic vaccination in this setting.Ultimately,it is increasingly recognized that elimination of HBV requires a treatment regimen based on a combination of multiple drugs.This review describes the rationale for progressive therapeutic interventions and discusses the latest findings in the field of HBV therapeutics.
基金National Key Research and Development Program of China,No.2021YFC2701704the National Clinical Medical Research Center for Geriatric Diseases,"Multicenter RCT"Research Project,No.NCRCG-PLAGH-20230010the Military Logistics Independent Research Project,No.2022HQZZ06.
文摘BACKGROUND Multiple myeloma(MM)is a terminal differentiated B-cell tumor disease characterized by clonal proliferation of malignant plasma cells and excessive levels of monoclonal immunoglobulins in the bone marrow.The translocation,(t)(4;14),results in high-risk MM with limited treatment alternatives.Thus,there is an urgent need for identification and validation of potential treatments for this MM subtype.Microarray data and sequencing information from public databases could offer opportunities for the discovery of new diagnostic or therapeutic targets.AIM To elucidate the molecular basis and search for potential effective drugs of t(4;14)MM subtype by employing a comprehensive approach.METHODS The transcriptional signature of t(4;14)MM was sourced from the Gene Expression Omnibus.Two datasets,GSE16558 and GSE116294,which included 17 and 15 t(4;14)MM bone marrow samples,and five and four normal bone marrow samples,respectively.After the differentially expressed genes were identified,the Cytohubba tool was used to screen for hub genes.Then,the hub genes were analyzed using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis.Using the STRING database and Cytoscape,protein–protein interaction networks and core targets were identified.Potential small-molecule drugs were identified and validated using the Connectivity Map database and molecular docking analysis,respectively.RESULTS In this study,a total of 258 differentially expressed genes with enriched functions in cancer pathways,namely cytokine receptor interactions,nuclear factor(NF)-κB signaling pathway,lipid metabolism,atherosclerosis,and Hippo signaling pathway,were identified.Ten hub genes(cd45,vcam1,ccl3,cd56,app,cd48,btk,ccr2,cybb,and cxcl12)were identified.Nine drugs,including ivermectin,deforolimus,and isoliquiritigenin,were predicted by the Connectivity Map database to have potential therapeutic effects on t(4;14)MM.In molecular docking,ivermectin showed strong binding affinity to all 10 identified targets,especially cd45 and cybb.Ivermectin inhibited t(4;14)MM cell growth via the NF-κB pathway and induced MM cell apoptosis in vitro.Furthermore,ivermectin increased reactive oxygen species accumulation and altered the mitochondrial membrane potential in t(4;14)MM cells.CONCLUSION Collectively,the findings offer valuable molecular insights for biomarker validation and potential drug development in t(4;14)MM diagnosis and treatment,with ivermectin emerging as a potential therapeutic alternative.
文摘Diabetic retinopathy (DR), a major micro-vascular complication of diabetes, has emerged as a leading cause of visual impairment and blindness among working adults in the worldwide. The pathobiology of DR involves multiple molecular pathways and is characterized chronic neurovascular degeneration. Current approaches to prevent or to treat DR are still far from satisfactory. Therefore, it is important to develop new therapeutic strategies for the prevention and treatment to DR. Pigment epithelium-derived factor (PEDF), a 50-kDa secreted glycoprotein, has been described as a multi-functional protein. Some emerging evidences indicate that PEDF are able to target multiple pathways exerting neurotropic, neuroprotective, anti-angiogenic, antivasopermeability, anti-inflammation, anti-thrombogenic and anti-oxidative effects in DR. In this review, we addressed the functions of PEDF in different pathways, which could lead to potential therapeutics on the treatment to DR.
基金We acknowledge financial support from the National Natural Science Foundation of China(81903574)the Fundamental Research Funds for the Central Universities(2019QNA7046,2020QNA7001).
文摘Therapeutic monoclonal antibodies have become one of the central components of the healthcare system and continuous efforts are made to bring innovative antibody therapeutics to patients in need.It is equally critical to acquire sufficient knowledge of their molecular structure and biological functions to ensure the efficacy and safety by incorporating new detection approaches since new challenges like individual differences and resistance are presented.Conventional techniques for determining antibody disposition including plasma drug concentration measurements using LC-MS or ELISA,and tissue distribution using immunohistochemistry and immunofluorescence are now complemented with molecular imaging modalities like positron emission tomography and near-infrared fluorescence imaging to obtain more dynamic information,while methods for characterization of antibody’s interaction with the target antigen as well as visualization of its cellular and intercellular behavior are still under development.Recent progress in detecting therapeutic antibodies,in particular,the development of methods suitable for illustrating the molecular dynamics,is described here.
基金Supported by National Natural Science Foundation of China,No.81672379 and No.81101858Natural Science Foundation of Shandong Province,China,No.ZR2016HM16.
文摘Gastric cancer(GC)is the fourth leading cause of cancer-related death.The occurrence and development of GC is a complex process involving multiple biological mechanisms.Although traditional regulation modulates molecular functions related to the occurrence and development of GC,the comprehensive mechanisms remain unclear.Ultraconserved region(UCR)refers to a genome sequence that is completely conserved in the homologous regions of the human,rat and mouse genomes,with 100%identity,without any insertions or deletions,and often located in fragile sites and tumour-related genes.The transcribed UCR(T-UCR)is transcribed from the UCR and is a new type of long noncoding RNA.Recent studies have found that the expression level of T-UCRs changes during the occurrence and development of GC,revealing a new mechanism underlying GC.Therefore,this article aims to review the relevant research on T-UCRs in GC,as well as the function of T-UCRs and their regulatory role in the occurrence and development of GC,to provide new strategies for GC diagnosis and treatment.
基金support of the Research Center for Advanced Materials Science(RCAMS)at King Khalid University Abha,Saudi Arabia,through Grant(KKU/RCAMS/22).
文摘The cytokine channel’s mechanism for self-regulation involves the application of antagonistic cytokines that are synthesized to connect to the receptors and release soluble cytokine receptors.The very first receptor antagonist of cytokine that was naturally present was interleukin-1 receptor antagonist(IL-1Ra).The IL-1Ra protein forms are disinfected from supernatants of cultured monocytes on stacked IgG.The family of IL-1 consists of IL-1α,IL-1βand IL-1Ra.Human monocytes regulate the production of IL-Ra.IL-Ra takes part in normal physiological functions by using specific antibodies,and acts as an anti-inflammatory agent.IL-Ra is synthesized in the tissues during the period of active disease and can be systematically measured and/or estimated.Maintenance of the levels of IL-Ra and IL-1 is the main factor for host resistance in patients during diseased conditions,as IL-Ra acts as an inherent regulator of various inflammatory responses.In this article,we focuse on how IL-Ra is synthesized and performs its functions once the inflammatory responses are activated.
基金supported by grants from the Zhejiang Provincial Natural Science Foundation of China(No.LR21H160001)"Pioneer"and"Leading Goose"R&DProgram of Zhejiang,China(No.2022C03004)+2 种基金the National Natural Science Foundation of China(No.82072646 to JC and No.82104214)Zhejiang Provincial Natural Science Foundation of China(No.LQ22H160016)Start-up Grant of Hangzhou Normal University(China)(No.4275C50222204072 to DH).
文摘B-cell CLL/lymphoma 9(BCL9)is considered a key developmental regulator and a well-established oncogenic driver in multiple cancer types,mainly through potentiating the Wnt/β-catenin signaling.However,increasing evidences indicate that BCL9 also plays multiple Wnt-independent roles.Herein,we summarized the updates of the canonical and non-canonical functions of BCL9 in cellular,physiological,or pathological processes.Moreover,we also concluded that the targeted inhibitors disrupt the interaction ofβ-catenin with BCL9 reported recently.
基金Natural Science Foundation of Chongqing Municipality,Grant/Award Number:cstc2020jcyjmsxmX0565National Natural Science Foundation of China,Grant/Award Number:82073137Natural Science Foundation of Jilin Province,Grant/Award Number:20200201353JC。
文摘Background:Non‐small cell lung cancer(NSCLC),including the lung squamous cell carcinoma(LUSC)and lung adenocarcinoma(LUAD)subtypes,is a malignant tumor type with a poor 5‐year survival rate.The identification of new powerful diagnostic biomarkers,prognostic biomarkers,and potential therapeutic targets in NSCLC is urgently required.Methods:The UCSC Xena,UALCAN,and GEO databases were used to screen and analyze differentially expressed genes,regulatory modes,and genetic/epigenetic alterations in NSCLC.The UCSC Xena database,GEO database,tissue microarray,and immunohistochemistry staining analyses were used to evaluate the diagnostic and prognostic values.Gain‐of‐function assays were performed to examine the roles.The ESTIMATE,TIMER,Linked Omics,STRING,and DAVID algorithms were used to analyze potential molecular mechanisms.Results:NR3C2 was identified as a potentially important molecule in NSCLC.NR3C2 is expressed at low levels in NSCLC,LUAD,and LUSC tissues,which is significantly related to the clinical indexes of these patients.Receiver operating characteristic curve analysis suggests that the altered NR3C2 expression patterns have diagnostic value in NSCLC,LUAD,and especially LUSC patients.Decreased NR3C2 expression levels can help predict poor prognosis in NSCLC and LUAD patients but not in LUSC patients.These results have been confirmed both with database analysis and real‐world clinical samples on a tissue microarray.Copy number variation contributes to low NR3C2 expression levels in NSCLC and LUAD,while promoter DNA methylation is involved in its downregulation in LUSC.Two NR3C2 promoter methylation sites have high sensitivity and specificity for LUSC diagnosis with clinical application potential.NR3C2 may be a key participant in NSCLC development and progression and is closely associated with the tumor microenvironment and immune cell infiltration.NR3C2 co‐expressed genes are involved in many cancer‐related signaling pathways,further supporting a potentially significant role of NR3C2 in NSCLC.Conclusions:NR3C2 is a novel potential diagnostic and prognostic biomarker and therapeutic target in NSCLC.
文摘AIM:To investigate effects of perirenal space blocking(PSB)on gastrointestinal function in patients with severe acute pancreatitis(SAP).METHODS:Forty patients with SAP were randomly allocated to receive PSB or no PSB(NPSB).All the SAP patients received specialized medical therapy(SMT).Patients in the PSB group received PSB+SMT when hospitalized and after diagnosis,whereas patients in the NPSB group only received SMT.A modifed gastrointestinal failure(GIF)scoring system was used to assess the gastrointestinal function in SAP patients after admission.Pain severity(visual analog scale,0 to100)was monitored every 24 h for 72 h.RESULTS:Modified GIF score decreased in both groups during the 10-d study period.The median score decrease was initially significantly greater in the PSB group than in the NPSB group after PSB was per-formed.During the 72-h study period,pain intensity decreased in both groups.The median pain decrease was significantly greater in the PSB group than in the NPSB group at single time points.Patients in the PSB group had significantly lower incidences of hospital mortality,multiple organ dysfunction syndrome,systemic inflammatory response syndrome,and pancreatic infection,and stayed in the intensive care unit for a shorter duration.However,no difference in terms of operation incidence was found between the two groups.CONCLUSION:PSB could ameliorate gastrointestinal dysfunction or failure during the early stage of SAP.Moreover,PSB administration could improve prognosis and decrease the mortality of SAP patients.
文摘Objective To study the damage of liver function after transcatheter arterial chemoembolization (TACE) with low-dose versus conventional-dose anticancer drugs in patients with hepatocellular carcinoma (HCC). Methods One hundred and twelve patients with unresectable HCC were randomly divided into two groups (A and B) to receive superselective TACE. Low-dose anticancer drugs including mitomycin C (MMC) 2 ～ 8 mg,epirubicin (EPI) 5 ～ 10 mg and carboplatin (CBP) 100 mg were used in group A (n = 52),and conventional-dose of anticancer drugs (MMC 10 mg,EPI 40 mg and CBP 300 mg)for patients in group B(n = 60). Lipiodol-anticancer drugs emulsion was injected into the feeding arteries of tumor and then followed by embolization of gelatin sponge (GS) or polyvinyl alcohol (PVA) particles. Laboratory examination of the liver function including Child-Pugh scores,total bilirubin (TBIL),albumin (ALB) and alanine aminotransferase (ALT) were evaluated respectively before TACE and at third day,one week and four weeks after this procedure. Results In both groups,TBIL,ALT,and Child-Pugh scores increased (P < 0.001 or P < 0.05) and ALB decreased (P < 0.001 or P < 0.01) at three days and one week after TACE. Four weeks after-procedure,all the parameters described above showed no significant difference than those before the procedure in group A (P > 0.05). On the contrary in group B,a significant difference (P < 0.05) was found in the comparison of these parameters (except ALT). Conclusion Superselective TACE with low-dose anticancer drugs may induce transient impairment of liver function in the patients with HCC,but those patients used conventional-dose of anticancer drugs frequently cause lasting and more serious worsening of liver function. (J Intervent Radiol,2006,15: 351-355)
基金This study was approved by the Ethic Committee of Basic Medical College of Qingdao University(Approval No.QDWMkj-2020-012).
文摘BACKGROUND Acute myelitis(AM)can lead to sudden sensory,motor and autonomic nervous dysfunction,which negatively affects their daily activities and quality of life,so it is necessary to explore optimization from a therapeutic perspective to curb the progression of the disease.AIM To investigate the effect of ganglioside(GM)combined with methylprednisolone sodium succinate(MPSS)on the curative effect and neurological function of patients with AM.METHODS First,we selected 108 AM patients visited between September 2019 and September 2022 and grouped them based on treatment modality,with 52 patients receiving gamma globulin(GG)+MPSS and 56 patients receiving GM+MPSS,assigned to the control group(Con)and observation group(Obs),respectively.The therapeutic effect,neurological function(sensory and motor function scores),adverse events(AEs),recovery(time to sphincter function recovery,time to limb muscle strength recovery above grade 2,and time to ambulation),inflammatory factors(IFs)[interleukin(IL)-6,C-reactive protein(CRP),and tumor necrosis factor(TNF)-α]and other data of the two groups were collected for evaluation and comparison.RESULTS The Obs had:(1)A significantly higher response rate of treatment than the Con;(2)Higher scores of sensory and motor functions after treatment that were higher than the baseline(before treatment)and higher than the Con levels;(3)Lower incidence rates of skin rash,gastrointestinal discomfort,dyslipidemia,osteoporosis and other AEs;(4)Faster posttreatment recovery of sphincter function,limb muscle strength and ambulation;and(5)Markedly lower posttreatment IL-6,CRP and TNF-αlevels than the baseline and the Con levels.CONCLUSION From the above,it can be seen that GM+MPSS is highly effective in treating AM,with a favorable safety profile comparable to that of GG+MPSS.It can significantly improve patients’neurological function,speed up their recovery and inhibit serum IFs.
基金Institute of Information&Communications Technology Planning&Evaluation(IITP)grant funded by Korea government(MSIT),Nos.2017-0-00961 and 2019-0-00102(to HDC)。
文摘We have previously found that long-term effects of exposure to radiofrequency electromagnetic fields in 5xFAD mice with severe late-stage Alzheimer’s disease reduced both amyloid-βdeposition and glial activation,including microglia.To examine whether this therapeutic effect is due to the regulation of activated microglia,we analyzed mic roglial gene expression profiles and the existence of microglia in the brain in this study.5xFAD mice at the age of 1.5 months were assigned to sham-and radiofrequency electromagnetic fields-exposed groups and then animals were exposed to 1950 MHz radiofrequency electromagnetic fields at a specific absorption rate of 5 W/kg for 2 hours/day and 5 days/week for 6 months.We conducted behavioral tests including the object recognition and Y-maze tests and molecular and histopathological analysis of amyloid precursor protein/a myloid-beta metabolism in brain tissue.We confirmed that radiofrequency electromagnetic field exposure for 6 months ameliorated cognitive impairment and amyloid-βdeposition.The expression levels of Iba1(pan-microglial marker)and colony-stimulating factor 1 receptor(CSF1R;regulates microglial prolife ration)in the hippocampus in 5xFAD mice treated with radiofrequency electromagnetic fields were significantly reduced compared with those of the sham-exposed group.Subsequently,we analyzed the expression levels of genes related to mic rogliosis and microglial function in the radiofrequency electromagnetic fields-exposed group compared to those of a CSF1R inhibitor(PLX3397)-treated group.Both radiofrequency electromagnetic fields and PLX3397 suppressed the levels of genes related to microgliosis(Csf1r,CD68,and Ccl6)and pro-inflammatory cytokine interleukin-1β.N otably,the expression levels of genes related to mic roglial function,including Trem2,Fcgr1α,Ctss,and Spi1,were decreased after long-term radiofrequency electromagnetic field exposure,which was also observed in response to microglial suppression by PLX3397.These results showed that radiofrequency electromagnetic fields ameliorated amyloid-βpathology and cognitive impairment by suppressing amyloid-βdeposition-induced microgliosis and their key regulator,CSF1R.
