MAFB is essential for regulating male-type urethral differentiation,and especially,its variation can contribute to hypospadias in mice.However,the potential mechanism is still unclear.Here we observed that the basic l...MAFB is essential for regulating male-type urethral differentiation,and especially,its variation can contribute to hypospadias in mice.However,the potential mechanism is still unclear.Here we observed that the basic leucine zipper(bZIP)transcription factor MAFB and CCAAT/enhancer-binding protein alpha(CEBPA)could promote human urothelium SV-HUC-1 growth.Moreover,MAFB and CEBPA expression were reduced in the prepuce tissues of hypospadias patients.Based on transcriptome sequencing analysis and Western blot,MAFB knockdown was found to suppress CEBPA protein expression and repress Wnt/β-catenin signaling in urothelium cells.Meanwhile,we observed blocked cell-cycle progression from the G1 to the S phase,inhibited cell proliferation,and activated apoptosis.Furthermore,MAFB could facilitate CEBPA transcription and regulate the proliferation of urothelium.The above results indicated that MAFB-mediated inhibition of urothelial SV-HUC-1 growth resulted from inhibiting the Wnt/β-catenin signaling pathway by down-regulating CEBPA.Our findings provide new insight into the understanding of genes associated with hypospadias and the pathogenic mechanism of this disorder.展开更多
Intervertebral disc degeneration(IDD)is a common chronic inflammatory degenerative disease that causes lower back pain.However,the underlying mechanisms of IDD remain unclear.Ferroptosis suppressor protein 1(FSP1)is a...Intervertebral disc degeneration(IDD)is a common chronic inflammatory degenerative disease that causes lower back pain.However,the underlying mechanisms of IDD remain unclear.Ferroptosis suppressor protein 1(FSP1)is a newly identified suppressor for ferroptosis.This study aims to investigate the role of FSP1 in IDD.Nucleus pulposus(NP)tissues in humans were collected and NP cells from rats were isolated to detect FSP1 expression pattern.The relationship between FSP1-mediated ferroptosis and apoptosis was identified using FSP1 inhibitor iFSP1.RNA sequencing was utilized to seek downstream molecules and related signaling pathways.Moreover,both exogenous recombinant FSP1 protein and endogenous small interfering RNA were implemented in this study to clarify the role of FSP1 in tumor necrosis factor-alpha(TNFα)-mediated NP cell apoptosis.Ultimately,the underlying mechanisms of FSP1-related signaling pathway in IDD were uncovered both in vitro and in vivo.As a result,FSP1 was up-regulated in human degenerative NP tissues and after TNFαstimulation.FSP1 inhibition by iFSP1 fails to trigger ferroptosis in NP cells while inhibiting TNFα-mediated apoptosis.Further experiments demonstrated that FSP1 was closely related to TNFα-reliant caspase 3 activation and mitochondrial damage.However,the exogenous addition of recombinant protein FSP1 does not induce cell death or intensify the efficacy of TNFα.Mechanically,FSP1 is involved in TNFα-mediated NF-κB signaling activation to accelerate the development of IDD.This study demonstrated that FSP1 promotes IDD through TNFα-reliant NF-κB signaling activation and caspase 3-dependent apoptosis.These findings suggested a novel therapeutic target for the treatment of IDD.展开更多
Although cell-cycle arrest,senescence,and apoptosis are well accepted as the classic barriers in tumorigenesis,recent studies indicate that metabolic regulation is equally important as a major checkpoint in cancer dev...Although cell-cycle arrest,senescence,and apoptosis are well accepted as the classic barriers in tumorigenesis,recent studies indicate that metabolic regulation is equally important as a major checkpoint in cancer development.It is well accepted that ferroptosis,an iron-dependent programmed cell death,acts as a new type of tumor suppression mechanism tightly linked with numerous metabolic pathways.SLC7A11 is a transmembrane cystine/glutamate transporter protein that plays a vital role in controlling ferroptosis in vivo.The levels of SLC7A11 are dynamically regulated by various types of stresses,such as oxidative stress,nutrient deprivation,endoplasmic reticulum stress,radiation,oncogenic stress,DNA damage,and immune stress.SLC7A11 can be transcriptionally regulated by both activators such as ATF4,NRF2,and ETS1,and repressors including BACH1,p53,ATF3,and STAT1 during stress responses.Moreover,SLC7A11 activity and its protein stability and cellular localization are also modulated upon stress.Patients’data show that SLC7A11 is overexpressed in various types of human cancers,and higher levels of SLC7A11 predict poorer overall survival.Growing evidence also suggests that targeting SLC7A11 is a promising approach in cancer therapy by effectively inhibiting tumor proliferation,invasion,and metastasis,as well as counteracting cancer stem cells and overcoming chemoresistance.This review highlights the regulation of SLC7A11 as an unconventional checkpoint in tumorigenesis through modulating ferroptotic responses under various types of stress.展开更多
Naked cuticle homolog 2(NKD2)has been recognized as an antagonist of Wnt/β-catenin signaling and a tumor suppressor.The role of NKD2 in osteoblast and osteoclast differentiation and the mechanism are not fully unders...Naked cuticle homolog 2(NKD2)has been recognized as an antagonist of Wnt/β-catenin signaling and a tumor suppressor.The role of NKD2 in osteoblast and osteoclast differentiation and the mechanism are not fully understood.In this study,we identified the up-regulation of NKD2 during osteoblast and adipocyte differentiation.Functional experiments revealed that NKD2 stimulated osteoblast differentiation and suppressed adipocyte formation.Furthermore,NKD2 down-regulated the expression of receptor activator of nuclear factor-κB ligand in bone marrow mesenchymal stem cells and inhibited osteoclast formation from osteoclast precursor cells.Mechanistic investigations revealed that the regulation of osteoblast and adipocyte differentiation by NKD2 involved Wnt/β-catenin and tuberous sclerosis complex subunit 1(TSC1)/mechanistic target of rapamycin complex 1(mTORC1)signaling pathways.Unlike in undifferentiated mesenchymal cells where NKD2 promoted Dishevelled-1 degradation,in the cells differentiating toward osteoblasts or adipocytes NKD2 down-regulated secreted frizzled related protein 1/4 expression and failed to destabilize Dishevelled-1,thereby activating Wnt/β-catenin signaling.Moreover,NKD2 bound to TSC1 and inhibited mTORC1 signaling.Further investigation uncovered an interplay between TSC1/mTORC1 and Wnt/β-catenin signaling pathways.Finally,transplantation of NKD2-overexpressing bone marrow mesenchymal stem cells into the marrow of mice increased osteoblasts,reduced osteoclasts and marrow fat,and partially prevented bone loss in ovariectomized mice.This study provides evidence that NKD2 in mesenchymal stem/progenitor cells reciprocally regulates the differentiation of osteoblasts and adipocytes by modulating Wnt/β-catenin and mTORC1 pathways and inhibits osteoclast formation by down-regulating receptor activator of nuclear factor-κB ligand.It suggests that NKD2 up-regulation may ameliorate postmenopausal bone loss.展开更多
Extrachromosomal circular DNA(eccDNA),a chromosome-independent circular DNA,has garnered significant attention due to its widespread distribution and intricate biogenesis in carcinoma.Existing research findings propos...Extrachromosomal circular DNA(eccDNA),a chromosome-independent circular DNA,has garnered significant attention due to its widespread distribution and intricate biogenesis in carcinoma.Existing research findings propose that multiple eccDNAs contribute to drug resistance in cancer treatments through complex and interrelated regulatory mechanisms.The unique structure and genetic properties of eccDNA increase tumor heterogeneity.This increased diversity is a result of eccDNA’s ability to stimulate oncogene remodeling and participate in anomalous splicing processes through chimeric cyclization and the reintegration of loop DNA back into the linear genome.Such actions promote oncogene amplification and silencing.eccDNA orchestrates protein interactions and modulates protein degradation by acting as a regulatory messenger.Moreover,it plays a pivotal role in modeling the tumor microenvironment and intensifying the stemness characteristics of tumor cells.This review presented detailed information about the biogenesis,distinguishing features,and functions of eccDNA,emphasized the role and mechanisms of eccDNA during cancer treatment,and further proposed the great potential of eccDNA in inspiring novel strategies for precision cancer therapy and facilitating the discovery of prognostic biomarkers for cancer.展开更多
Multiple myeloma(MM)patients with chromosome 1q gain(1q+)are clinically and biologically heterogeneous.The underlying molecular mechanisms are still under investigation,while the identification of targets for effectiv...Multiple myeloma(MM)patients with chromosome 1q gain(1q+)are clinically and biologically heterogeneous.The underlying molecular mechanisms are still under investigation,while the identification of targets for effective therapy of this subgroup of MM patients is urgently needed.We aimed to investigate the clinical significance and the regulatory mechanisms of insulin-like growth factor 2 messenger RNA(mRNA)binding protein 1(IGF2BP1),a N6-methyladenosine(m6A)reader,in MM patients with 1q+.We found that MM patients with 1q+exhibit a significantly higher level of IGF2BP1 mRNA than controls,while higher IGF2BP1 expression predicted a worse prognosis in MM patients with 1q+.IGF2BP1 overexpression promoted cell proliferation and G1-to-S phase transition of the cell cycle in NCI-H929 cells.Through comprehensive in silico analyses of existing public datasets and in-house generated high-throughput sequencing datasets,along with in vitro experiments,we identified CDC5L as a target of IGFBP1,which can bind to the m6A sites of CDC5L mRNA to up-regulate its protein abundance.Higher CDC5L expression also predicted a worse prognosis of MM patients with 1q+.Moreover,both knockdown and mutation of CDC5L attenuated the pro-proliferative effect of IGF2BP1.Furthermore,IGF2BP1 inhibitor BTYNB effectively inhibited CDC5L expression in MM cells with 1q+and suppressed the proliferation of these cells in vitro and in vivo.Therefore,IGF2BP1 acts as a post-transcriptional enhancer of CDC5L in an m6A-dependent manner to promote the proliferation of MM cells with 1q+.Our work identified a novel IGF2BP1-CDC5L axis and provided new insight into developing targeted therapeutics for MM patients with 1q+.展开更多
Posttranscriptional RNA modification is an important mode of epigenetic regulation in various biological and pathological contexts.N6,2′-O-dimethyladenosine(m6Am)is one of the most abundant methylation modifications ...Posttranscriptional RNA modification is an important mode of epigenetic regulation in various biological and pathological contexts.N6,2′-O-dimethyladenosine(m6Am)is one of the most abundant methylation modifications in mammals and usually occurs at the first transcribed nucleotide.Accumulating evidence indicates that m6Am modifications have important roles in RNA metabolism and physiological and pathological processes.PCIF1(phosphorylated C-terminal domain interacting factor 1)is a protein that can bind to the phosphorylated C-terminal domain of RNA polymeraseⅡthrough its WW domain.PCIF1 is named after this binding ability.Recently,PCIF1 has been identified as a cap-specific adenine N6-methyltransferase responsible for m6Am formation.Discovered as the sole m6Am methyltransferase for mammalian mRNA,PCIF1 has since received more extensive and in-depth study.Dysregulation of PCIF1 contributes to various pathological processes.Targeting PCIF1 may hold promising therapeutic significance.In this review,we provide an overview of the current knowledge of PCIF1.We explore the current understanding of the structure and the biological characteristics of PCIF1.We further review the molecular mechanisms of PCIF1 in cancer and viral infection and discuss its therapeutic potential.展开更多
Exosomes,extracellular vesicles originating from endosomes,were discovered in the late 1980s and their function in intercellular communication has since garnered considerable interest.Exosomes are lipid bilayer-coated...Exosomes,extracellular vesicles originating from endosomes,were discovered in the late 1980s and their function in intercellular communication has since garnered considerable interest.Exosomes are lipid bilayer-coated vesicles that range in size from 30 to 150 nm and appear as sacs under the electron microscope.Exosome secretion is crucial for cell-to-cell contact in both normal physiology and the development and spread of tumors.Furthermore,cancer cells can secrete more exosomes than normal cells.Scientists believe that intercellular communication in the complex tissue environment of the human body is an important reason for cancer cell invasion and metastasis.For example,some particles containing regulatory molecules are secreted in the tumor microenvironment,including exosomes.Then the contents of exosomes can be released by donor cells into the environment and interact with recipient cells to promote the migration and invasion of tumor cells.Therefore,in this review,we summarized the biogenesis of exosome,as well as exosome cargo and related roles.More importantly,this review introduces and discusses the factors that have been reported to affect exosome secretion in tumors and highlights the important role of exosomes in tumors.展开更多
microRNAs(miRNAs)are short single-stranded non-coding RNAs between 21 and 25 nt in length in eukaryotic organisms,which control post-transcriptional gene expression.Through complementary base pairing,miRNAs generally ...microRNAs(miRNAs)are short single-stranded non-coding RNAs between 21 and 25 nt in length in eukaryotic organisms,which control post-transcriptional gene expression.Through complementary base pairing,miRNAs generally bind to their target messenger RNAs and repress protein production by destabilizing the messenger RNA and translational silencing.They regulate almost all life activities,such as cell proliferation,differentiation,apoptosis,tumorigenesis,and host–pathogen interactions.Methylation modification is the most common RNA modification in eukaryotes.miRNA methylation exists in different types,mainly N6-methyladenosine,5-methylcytosine,and 7-methylguanine,which can change the expression level and biological mode of action of miRNAs and improve the activity of regulating gene expression in a very fine-tuned way with flexibility.In this review,we will summarize the recent findings concerning methylation modifications of miRNA,focusing on their biogenesis and the potential role of miRNA fate and functions.展开更多
Human hepatitis B virus(HBV)infection is the major cause of acute and chronic hepatitis B,liver cirrhosis,and hepatocellular carcinoma.Although the application of prophylactic vaccination programs has successfully pre...Human hepatitis B virus(HBV)infection is the major cause of acute and chronic hepatitis B,liver cirrhosis,and hepatocellular carcinoma.Although the application of prophylactic vaccination programs has successfully prevented the trend of increasing HBV infection prevalence,the number of HBV-infected people remains very high.Approved therapeutic management efficiently suppresses viral replication;however,HBV infection is rarely completely resolved.The major reason for therapeutic failure is the persistence of covalently closed circular DNA(cccDNA),which forms viral minichromosomes by combining with histone and nonhistone proteins in the nucleus.Increasing evidence indicates that chromatin-modifying enzymes,viral proteins,and noncoding RNAs are essential for modulating the function of cccDNA.Therefore,a deeper understanding of the regulatory mechanism underlying cccDNA transcription will contribute to the development of a cure for chronic hepatitis B.This review summarizes the current knowledge of cccDNA biology,the regulatory mechanisms underlying cccDNA transcription,and novel anti-HBV approaches for eliminating cccDNA transcription.展开更多
Estrogen deficiency is considered the most important cause of postmenopausal osteoporosis.However,the underlying mechanism is still not completely understood.In this study,progranulin(PGRN)was isolated as a key regula...Estrogen deficiency is considered the most important cause of postmenopausal osteoporosis.However,the underlying mechanism is still not completely understood.In this study,progranulin(PGRN)was isolated as a key regulator of bone mineral density in postmenopausal women through high throughput proteomics screening.In addition,PGRN-deficient mice exhibited significantly lower bone mass than their littermates in an ovariectomy-induced osteoporosis model.Furthermore,estrogen-mediated inhibition of osteoclastogenesis and bone resorption as well as its protection against ovariectomy-induced bone loss largely depended on PGRN.Mechanistic studies revealed the existence of a positive feedback regulatory loop between PGRN and estrogen signaling.In addition,loss of PGRN led to the reduction of estrogen receptorα,the important estrogen receptor involved in estrogen regulation of osteoporosis,through enhancing its degradation via K48-linked ubiquitination.These findings not only provide a previously unrecognized interplay between PGRN and estrogen signaling in regulating osteoclastogenesis and osteoporosis but may also present a new therapeutic approach for the prevention and treatment of postmenopausal osteoporosis by targeting PGRN/estrogen receptorα.展开更多
Digestive-system cancers represent major threats to human health;however,the mechanisms underlying tumorigenesis and radiochemotherapy resistance have remained elusive.Therefore,an urgent need exists for identifying k...Digestive-system cancers represent major threats to human health;however,the mechanisms underlying tumorigenesis and radiochemotherapy resistance have remained elusive.Therefore,an urgent need exists for identifying key drivers of digestive system tumorigenesis and novel targeted therapeutics.The checkpoint kinase 2(Chk2)regulates cell-cycle progression,and Chk2 dysregulation or Chk2 mutations can lead to the development of various cancers,which makes Chk2 an important research topic.This review summarizes the roles of Chk2 in DNA-damage responses,cell-cycle regulation,autophagy,and homeostasis maintenance.We describe relationships between tumorigenesis and cell-cycle dysregulation induced by Chk2 mutations.In addition,we summarize evidence indicating that Chk2 can serve as a novel therapeutic target,based on its contributions to radiochemotherapy-resistance reversion and progress made in developing antitumor agents against Chk2.The prevailing evidence supports the conclusion that further research on Chk2 will provide a deeper understanding of digestive-system tumorigenesis and should suggest novel therapeutic targets.展开更多
Osteoarthritis (OA) is a debilitating chronic joint disease affecting large populations of patients, especially the elderly. The pathological mechanisms of OA are currently unknown. Multiple risk factors are involved ...Osteoarthritis (OA) is a debilitating chronic joint disease affecting large populations of patients, especially the elderly. The pathological mechanisms of OA are currently unknown. Multiple risk factors are involved in OA development. Among these risk factors, alterations of mechanical loading in the joint leading to changes in biological signaling pathways have been known as a key event in OA development. The importance of AMPK-β-catenin-Runx2 signaling in the initiation and progression of OA has been recognized in recent years. In this review, we discuss the recent progress in understanding the role of this signaling pathway and the underlying interaction mechanisms during OA development. We also discuss the drug development aiming to target this signaling pathway for OA treatment.展开更多
In precision cancer therapy,addressing intra-tumor heterogeneity poses a significant obstacle.Due to the heterogeneity of each cell subtype and between cells within the tumor,the sensitivity and resistance of differen...In precision cancer therapy,addressing intra-tumor heterogeneity poses a significant obstacle.Due to the heterogeneity of each cell subtype and between cells within the tumor,the sensitivity and resistance of different patients to targeted drugs,chemotherapy,etc.,are inconsistent.Concerning a specific tumor type,many feasible treatments or combinations can be used by specifically targeting the tumor microenvironment.To solve this problem,it is necessary to further study the tumor microenvironment.Single-cell sequencing techniques can dissect distinct tumor cell populations by isolating cells and using statistical computational methods.This technology may assist in the selection of targeted combination therapy,and the obtained cell subset information is crucial for the rational application of targeted therapy.In this review,we summarized the research and application advances of single-cell sequencing technology in the tumor microenvironment,including the most commonly used single-cell genomic and transcriptomic sequencing,and their future development direction was proposed.The application of single-cell sequencing technology has been expanded to include epigenomics,proteomics,metabolomics,and microbiome analysis.The integration of these different omics approaches has significantly advanced the development of single-cell multiomics sequencing technology.This innovative approach holds immense potential for various fields,such as biological research and medical investigations.Finally,we discussed the advantages and disadvantages of using single-cell sequencing to explore the tumor microenvironment.展开更多
It is estimated that infertility impacts 8%-12%of reproductive-aged couples worldwide.Female infertility accounts for 37%of causes among infertile couples,and ovulatory dysfunction is regarded as its most common facto...It is estimated that infertility impacts 8%-12%of reproductive-aged couples worldwide.Female infertility accounts for 37%of causes among infertile couples,and ovulatory dysfunction is regarded as its most common factor.1 cUL4B belongs to the Cullin family,whose members are the scaffolding proteins of Cullin-RING E3 ligases(CRLs).Human CUL4B gene mutations result in X-linked mental retardation syndromes.In addition to mental retardation,patients have symptoms such as short stature,obesity,and hypogonadism.展开更多
Nowadays,although the treatment and diagnostic approaches have been improved,lung adenocarcinoma(LUAD)is still the leading cause of cancer-related death in the world with overall survival of less than five yearsi.Diag...Nowadays,although the treatment and diagnostic approaches have been improved,lung adenocarcinoma(LUAD)is still the leading cause of cancer-related death in the world with overall survival of less than five yearsi.Diagnosis of LUAD in the early stage is still a challenge,resulting from that early symptoms are not obvious2,which leads to the fact that most patients eventually die from cancer progression and chemotherapy resistance.LUAD is reported to be associated with the MAPK pathway,however,the mechanism at the cellular and genetic levels has not been clearly elucidated.Therefore,functional exploration of LUAD-and MAPK pathway-related genes is essential for understanding the pathogenesis of LUAD and exploring therapeutic measures.Figure S1 illustrates the flowchart of this study.展开更多
Germ cell arrest is one kind of important disease in nonobstructive azoospermia(NOA)including spermatogonia arrest,spermatocyte arrest,and round spermatid arrest.1 There is an urgent need to explore the molecular mech...Germ cell arrest is one kind of important disease in nonobstructive azoospermia(NOA)including spermatogonia arrest,spermatocyte arrest,and round spermatid arrest.1 There is an urgent need to explore the molecular mechanisms underlying germ cell arrest,which are essentially unknown and could provide not only a promising approach for therapy but also novel possibilities for developing male contraceptives.展开更多
Krabbe disease,also known as globoid cell leukodystrophy,is a rare lysosomal storage disorder.It is primarily caused by mutations in the GALC gene on chromosome 14q31,leading to GALC enzyme deficiency in lysosomes.Thi...Krabbe disease,also known as globoid cell leukodystrophy,is a rare lysosomal storage disorder.It is primarily caused by mutations in the GALC gene on chromosome 14q31,leading to GALC enzyme deficiency in lysosomes.This results in the accumulation of toxic substrate psychosine in the nervous systems.1 Currently,hematopoietic stem cell transplantation is the only available treatment,offering only a delay in neurological deterioration.Gene therapy,particularly using recombinant adeno-associated viruses(AAVs),shows promise for treating genetic diseases by introducing functional genes into target cells.展开更多
In recent years,molecular diagnostics has become pivotal in the detection of polycystic kidney disease(PKD).1 Nevertheless,given the extensive genomic architecture,allelic heterogeneity,and dispersed mutations in affi...In recent years,molecular diagnostics has become pivotal in the detection of polycystic kidney disease(PKD).1 Nevertheless,given the extensive genomic architecture,allelic heterogeneity,and dispersed mutations in affiliated genes,the translation of its clinical prospects is constrained.2 Moreover,summarizing the pertinent literature within the past decade reveals that the majority of studies predominantly focus on three main genes(PKD1,PKD2,and PKHD1),resulting in a limited scope of genes considered(Table S1).In the present investigation,endeavoring to supersede the limitations of traditional genetic diagnosis methods,we employed next-generation sequencing to meticulously interrogate the entire coding domains and exon-intron junctions of 15 pre-eminent genes(Table S2).展开更多
Sepsis,a life-threatening condition triggered by a dysregulated host response to infection,remains a major challenge for therapeutic intervention.Despite the growing interest in immunomodulatory strategies for sepsis ...Sepsis,a life-threatening condition triggered by a dysregulated host response to infection,remains a major challenge for therapeutic intervention.Despite the growing interest in immunomodulatory strategies for sepsis treatment,the effects and mechanisms of these approaches on the organ-specific inflammatory and immunosuppressive states induced by sepsis are poorly understood.According to existing studies,capsaicin(CPS)has pharmacological effects such as analgesic,antipruritic,hypolipidemia,hypoglycemia,anti-inflammatory and antibacterial,and antitumor activity.1 However,the effectiveness of CPs in treating sepsis is still unknown.展开更多
基金financed by the National Natural Science Foundation of China(No.81970571)the Natural Science Foundation of Chongqing Municipality,China(No.CSTB2022NSCQ-MSX1001)the Program for Youth Innovation in Future Medicine,Chongqing Medical University(No.W0109).
文摘MAFB is essential for regulating male-type urethral differentiation,and especially,its variation can contribute to hypospadias in mice.However,the potential mechanism is still unclear.Here we observed that the basic leucine zipper(bZIP)transcription factor MAFB and CCAAT/enhancer-binding protein alpha(CEBPA)could promote human urothelium SV-HUC-1 growth.Moreover,MAFB and CEBPA expression were reduced in the prepuce tissues of hypospadias patients.Based on transcriptome sequencing analysis and Western blot,MAFB knockdown was found to suppress CEBPA protein expression and repress Wnt/β-catenin signaling in urothelium cells.Meanwhile,we observed blocked cell-cycle progression from the G1 to the S phase,inhibited cell proliferation,and activated apoptosis.Furthermore,MAFB could facilitate CEBPA transcription and regulate the proliferation of urothelium.The above results indicated that MAFB-mediated inhibition of urothelial SV-HUC-1 growth resulted from inhibiting the Wnt/β-catenin signaling pathway by down-regulating CEBPA.Our findings provide new insight into the understanding of genes associated with hypospadias and the pathogenic mechanism of this disorder.
基金supported in part by the National Natural Science Foundation of China(No.81874022 and 82172483 to Xinyu Liu,No.82102522 to Lianlei Wang)Key R&D Project of Shandong Province(China)(No.2022CXGC010503 to Xinyu Liu)+2 种基金Shandong Natural Science Foundation(No.ZR202102210113 to Lianlei Wang)Shandong Province Taishan Scholar Project(No.tsqn 202211317 to Lianlei Wang)National High Level Hospital Clinical Research Funding(No.2022-PUMCH-D-004).
文摘Intervertebral disc degeneration(IDD)is a common chronic inflammatory degenerative disease that causes lower back pain.However,the underlying mechanisms of IDD remain unclear.Ferroptosis suppressor protein 1(FSP1)is a newly identified suppressor for ferroptosis.This study aims to investigate the role of FSP1 in IDD.Nucleus pulposus(NP)tissues in humans were collected and NP cells from rats were isolated to detect FSP1 expression pattern.The relationship between FSP1-mediated ferroptosis and apoptosis was identified using FSP1 inhibitor iFSP1.RNA sequencing was utilized to seek downstream molecules and related signaling pathways.Moreover,both exogenous recombinant FSP1 protein and endogenous small interfering RNA were implemented in this study to clarify the role of FSP1 in tumor necrosis factor-alpha(TNFα)-mediated NP cell apoptosis.Ultimately,the underlying mechanisms of FSP1-related signaling pathway in IDD were uncovered both in vitro and in vivo.As a result,FSP1 was up-regulated in human degenerative NP tissues and after TNFαstimulation.FSP1 inhibition by iFSP1 fails to trigger ferroptosis in NP cells while inhibiting TNFα-mediated apoptosis.Further experiments demonstrated that FSP1 was closely related to TNFα-reliant caspase 3 activation and mitochondrial damage.However,the exogenous addition of recombinant protein FSP1 does not induce cell death or intensify the efficacy of TNFα.Mechanically,FSP1 is involved in TNFα-mediated NF-κB signaling activation to accelerate the development of IDD.This study demonstrated that FSP1 promotes IDD through TNFα-reliant NF-κB signaling activation and caspase 3-dependent apoptosis.These findings suggested a novel therapeutic target for the treatment of IDD.
基金supported by the National Cancer Institute of the National Institutes of Health(USA)(No.R35CA253059,RO1CA258390,RO1CA254970 to W.G.).
文摘Although cell-cycle arrest,senescence,and apoptosis are well accepted as the classic barriers in tumorigenesis,recent studies indicate that metabolic regulation is equally important as a major checkpoint in cancer development.It is well accepted that ferroptosis,an iron-dependent programmed cell death,acts as a new type of tumor suppression mechanism tightly linked with numerous metabolic pathways.SLC7A11 is a transmembrane cystine/glutamate transporter protein that plays a vital role in controlling ferroptosis in vivo.The levels of SLC7A11 are dynamically regulated by various types of stresses,such as oxidative stress,nutrient deprivation,endoplasmic reticulum stress,radiation,oncogenic stress,DNA damage,and immune stress.SLC7A11 can be transcriptionally regulated by both activators such as ATF4,NRF2,and ETS1,and repressors including BACH1,p53,ATF3,and STAT1 during stress responses.Moreover,SLC7A11 activity and its protein stability and cellular localization are also modulated upon stress.Patients’data show that SLC7A11 is overexpressed in various types of human cancers,and higher levels of SLC7A11 predict poorer overall survival.Growing evidence also suggests that targeting SLC7A11 is a promising approach in cancer therapy by effectively inhibiting tumor proliferation,invasion,and metastasis,as well as counteracting cancer stem cells and overcoming chemoresistance.This review highlights the regulation of SLC7A11 as an unconventional checkpoint in tumorigenesis through modulating ferroptotic responses under various types of stress.
基金funded by the National Natural Science Foundation of China(No.82072389,82272444,81972033).
文摘Naked cuticle homolog 2(NKD2)has been recognized as an antagonist of Wnt/β-catenin signaling and a tumor suppressor.The role of NKD2 in osteoblast and osteoclast differentiation and the mechanism are not fully understood.In this study,we identified the up-regulation of NKD2 during osteoblast and adipocyte differentiation.Functional experiments revealed that NKD2 stimulated osteoblast differentiation and suppressed adipocyte formation.Furthermore,NKD2 down-regulated the expression of receptor activator of nuclear factor-κB ligand in bone marrow mesenchymal stem cells and inhibited osteoclast formation from osteoclast precursor cells.Mechanistic investigations revealed that the regulation of osteoblast and adipocyte differentiation by NKD2 involved Wnt/β-catenin and tuberous sclerosis complex subunit 1(TSC1)/mechanistic target of rapamycin complex 1(mTORC1)signaling pathways.Unlike in undifferentiated mesenchymal cells where NKD2 promoted Dishevelled-1 degradation,in the cells differentiating toward osteoblasts or adipocytes NKD2 down-regulated secreted frizzled related protein 1/4 expression and failed to destabilize Dishevelled-1,thereby activating Wnt/β-catenin signaling.Moreover,NKD2 bound to TSC1 and inhibited mTORC1 signaling.Further investigation uncovered an interplay between TSC1/mTORC1 and Wnt/β-catenin signaling pathways.Finally,transplantation of NKD2-overexpressing bone marrow mesenchymal stem cells into the marrow of mice increased osteoblasts,reduced osteoclasts and marrow fat,and partially prevented bone loss in ovariectomized mice.This study provides evidence that NKD2 in mesenchymal stem/progenitor cells reciprocally regulates the differentiation of osteoblasts and adipocytes by modulating Wnt/β-catenin and mTORC1 pathways and inhibits osteoclast formation by down-regulating receptor activator of nuclear factor-κB ligand.It suggests that NKD2 up-regulation may ameliorate postmenopausal bone loss.
基金supported by grants from the National Natural Science Foundation of China(No.82073281,8157346282073884,U20A20413)Shenyang S&T Projects(Liaoning,China)(No.20-204-4-22)+1 种基金Science and Technology Innovation Team Project of China Medical University(No.CXTD2022007)Supporting the High-Quality Development of Science and Technology Funding Projects at China Medical University(No.2022011963-JH2/202).
文摘Extrachromosomal circular DNA(eccDNA),a chromosome-independent circular DNA,has garnered significant attention due to its widespread distribution and intricate biogenesis in carcinoma.Existing research findings propose that multiple eccDNAs contribute to drug resistance in cancer treatments through complex and interrelated regulatory mechanisms.The unique structure and genetic properties of eccDNA increase tumor heterogeneity.This increased diversity is a result of eccDNA’s ability to stimulate oncogene remodeling and participate in anomalous splicing processes through chimeric cyclization and the reintegration of loop DNA back into the linear genome.Such actions promote oncogene amplification and silencing.eccDNA orchestrates protein interactions and modulates protein degradation by acting as a regulatory messenger.Moreover,it plays a pivotal role in modeling the tumor microenvironment and intensifying the stemness characteristics of tumor cells.This review presented detailed information about the biogenesis,distinguishing features,and functions of eccDNA,emphasized the role and mechanisms of eccDNA during cancer treatment,and further proposed the great potential of eccDNA in inspiring novel strategies for precision cancer therapy and facilitating the discovery of prognostic biomarkers for cancer.
基金supported by the National Natural Science Foundation of China(No.82100215)Natural Science Foundation of Shanghai,China(No.22ZR1411400)Natural Science Foundation of Fujian Province,China(No.2023J05291).
文摘Multiple myeloma(MM)patients with chromosome 1q gain(1q+)are clinically and biologically heterogeneous.The underlying molecular mechanisms are still under investigation,while the identification of targets for effective therapy of this subgroup of MM patients is urgently needed.We aimed to investigate the clinical significance and the regulatory mechanisms of insulin-like growth factor 2 messenger RNA(mRNA)binding protein 1(IGF2BP1),a N6-methyladenosine(m6A)reader,in MM patients with 1q+.We found that MM patients with 1q+exhibit a significantly higher level of IGF2BP1 mRNA than controls,while higher IGF2BP1 expression predicted a worse prognosis in MM patients with 1q+.IGF2BP1 overexpression promoted cell proliferation and G1-to-S phase transition of the cell cycle in NCI-H929 cells.Through comprehensive in silico analyses of existing public datasets and in-house generated high-throughput sequencing datasets,along with in vitro experiments,we identified CDC5L as a target of IGFBP1,which can bind to the m6A sites of CDC5L mRNA to up-regulate its protein abundance.Higher CDC5L expression also predicted a worse prognosis of MM patients with 1q+.Moreover,both knockdown and mutation of CDC5L attenuated the pro-proliferative effect of IGF2BP1.Furthermore,IGF2BP1 inhibitor BTYNB effectively inhibited CDC5L expression in MM cells with 1q+and suppressed the proliferation of these cells in vitro and in vivo.Therefore,IGF2BP1 acts as a post-transcriptional enhancer of CDC5L in an m6A-dependent manner to promote the proliferation of MM cells with 1q+.Our work identified a novel IGF2BP1-CDC5L axis and provided new insight into developing targeted therapeutics for MM patients with 1q+.
基金supported by grants from the National Natural Science Foundation of China(No.81272372)Zhongnan Hospital of Wuhan University Science,Technology and Innovation Seed Fund(Wuhan,China)(No.PTXM2022017)The project was sponsored by SRF for ROCS,SEM.
文摘Posttranscriptional RNA modification is an important mode of epigenetic regulation in various biological and pathological contexts.N6,2′-O-dimethyladenosine(m6Am)is one of the most abundant methylation modifications in mammals and usually occurs at the first transcribed nucleotide.Accumulating evidence indicates that m6Am modifications have important roles in RNA metabolism and physiological and pathological processes.PCIF1(phosphorylated C-terminal domain interacting factor 1)is a protein that can bind to the phosphorylated C-terminal domain of RNA polymeraseⅡthrough its WW domain.PCIF1 is named after this binding ability.Recently,PCIF1 has been identified as a cap-specific adenine N6-methyltransferase responsible for m6Am formation.Discovered as the sole m6Am methyltransferase for mammalian mRNA,PCIF1 has since received more extensive and in-depth study.Dysregulation of PCIF1 contributes to various pathological processes.Targeting PCIF1 may hold promising therapeutic significance.In this review,we provide an overview of the current knowledge of PCIF1.We explore the current understanding of the structure and the biological characteristics of PCIF1.We further review the molecular mechanisms of PCIF1 in cancer and viral infection and discuss its therapeutic potential.
基金supported by grants from the National Natural Science Foundation of China(No.82272624)the Natural Science Foundation of Jiangsu Province,China(No.BK20211105)+6 种基金the Plan of Jiangsu Provincial Medical Key Discipline(China)(No.ZDXK202240)the Social Development Foundation of Nantong City,Jiangsu,China(No.MS22022044,JC22022001,JCZ2022027)the Health Project of Nantong City,Jiangsu,China(No.MS2022056)the Postgraduate Research and Practice Innovation Program of Jiangsu Province,China(No.SJCX21_1452,KYCX21_3112,KYCX23_3419)Jiangsu Provincial Research Hospital(China)(YJXYY202204)the Jiangsu Administration of Traditional Chinese Medicine(China)(JD2022SZ07)Teaching Research Project of Affiliated Hospital of Nantong University(China)(Tfj22002).
文摘Exosomes,extracellular vesicles originating from endosomes,were discovered in the late 1980s and their function in intercellular communication has since garnered considerable interest.Exosomes are lipid bilayer-coated vesicles that range in size from 30 to 150 nm and appear as sacs under the electron microscope.Exosome secretion is crucial for cell-to-cell contact in both normal physiology and the development and spread of tumors.Furthermore,cancer cells can secrete more exosomes than normal cells.Scientists believe that intercellular communication in the complex tissue environment of the human body is an important reason for cancer cell invasion and metastasis.For example,some particles containing regulatory molecules are secreted in the tumor microenvironment,including exosomes.Then the contents of exosomes can be released by donor cells into the environment and interact with recipient cells to promote the migration and invasion of tumor cells.Therefore,in this review,we summarized the biogenesis of exosome,as well as exosome cargo and related roles.More importantly,this review introduces and discusses the factors that have been reported to affect exosome secretion in tumors and highlights the important role of exosomes in tumors.
基金supported by the Natural Science Foundation of Jilin Province,China(No.20230101147JC)the National Natural Science Foundation of China(No.31970154)the China Postdoctoral Science Foundation(No.2022TQ0119).
文摘microRNAs(miRNAs)are short single-stranded non-coding RNAs between 21 and 25 nt in length in eukaryotic organisms,which control post-transcriptional gene expression.Through complementary base pairing,miRNAs generally bind to their target messenger RNAs and repress protein production by destabilizing the messenger RNA and translational silencing.They regulate almost all life activities,such as cell proliferation,differentiation,apoptosis,tumorigenesis,and host–pathogen interactions.Methylation modification is the most common RNA modification in eukaryotes.miRNA methylation exists in different types,mainly N6-methyladenosine,5-methylcytosine,and 7-methylguanine,which can change the expression level and biological mode of action of miRNAs and improve the activity of regulating gene expression in a very fine-tuned way with flexibility.In this review,we will summarize the recent findings concerning methylation modifications of miRNA,focusing on their biogenesis and the potential role of miRNA fate and functions.
基金supported by funds from the National Key R&D Program of China(No.2022YFA1303600)the National Natural Science Foundation of China(No.82273423,82202501)+2 种基金Scientific and Technological Research Program of Chongqing Municipal Education Commission of China(No.KJQN202100429)Natural Science Foundation Project of Chongqing,China(No.CSTB2022NSCQ-MSX0864)College Young Teachers Fund of the Fok Ying Tung Education Foundation(China)(No.171100).
文摘Human hepatitis B virus(HBV)infection is the major cause of acute and chronic hepatitis B,liver cirrhosis,and hepatocellular carcinoma.Although the application of prophylactic vaccination programs has successfully prevented the trend of increasing HBV infection prevalence,the number of HBV-infected people remains very high.Approved therapeutic management efficiently suppresses viral replication;however,HBV infection is rarely completely resolved.The major reason for therapeutic failure is the persistence of covalently closed circular DNA(cccDNA),which forms viral minichromosomes by combining with histone and nonhistone proteins in the nucleus.Increasing evidence indicates that chromatin-modifying enzymes,viral proteins,and noncoding RNAs are essential for modulating the function of cccDNA.Therefore,a deeper understanding of the regulatory mechanism underlying cccDNA transcription will contribute to the development of a cure for chronic hepatitis B.This review summarizes the current knowledge of cccDNA biology,the regulatory mechanisms underlying cccDNA transcription,and novel anti-HBV approaches for eliminating cccDNA transcription.
基金supported by the grants from China Scholarship Council(No.201505320002)the National Institutes of Health(No.R01AR062207,R01AR061484,R01AR076900,R01NS103931)+3 种基金Young Medical Talents Program of Jiangsu Province,China(No.QNRC2016878)National Key R&D Program of China(No.SQ2021YFC2501702)Natural Science Foundation of China(No.82072474)Clinical Medicine Technology Project of Jiangsu Province,China(No.BE2019661).
文摘Estrogen deficiency is considered the most important cause of postmenopausal osteoporosis.However,the underlying mechanism is still not completely understood.In this study,progranulin(PGRN)was isolated as a key regulator of bone mineral density in postmenopausal women through high throughput proteomics screening.In addition,PGRN-deficient mice exhibited significantly lower bone mass than their littermates in an ovariectomy-induced osteoporosis model.Furthermore,estrogen-mediated inhibition of osteoclastogenesis and bone resorption as well as its protection against ovariectomy-induced bone loss largely depended on PGRN.Mechanistic studies revealed the existence of a positive feedback regulatory loop between PGRN and estrogen signaling.In addition,loss of PGRN led to the reduction of estrogen receptorα,the important estrogen receptor involved in estrogen regulation of osteoporosis,through enhancing its degradation via K48-linked ubiquitination.These findings not only provide a previously unrecognized interplay between PGRN and estrogen signaling in regulating osteoclastogenesis and osteoporosis but may also present a new therapeutic approach for the prevention and treatment of postmenopausal osteoporosis by targeting PGRN/estrogen receptorα.
基金supported by the National Natural Science Foundation of China(No.82100700 to F.Y.)the China Postdoctoral Science Foundation(No.2020M670101ZX to F.Y.)+1 种基金the Fundamental Scientific Research Project from the Educational Department of Liaoning Province,China(No.LJKMZ20221191 to F.Y.)the 345 Talent Project of Shengjing Hospital of China Medical University(No.52-30B to F.Y.).
文摘Digestive-system cancers represent major threats to human health;however,the mechanisms underlying tumorigenesis and radiochemotherapy resistance have remained elusive.Therefore,an urgent need exists for identifying key drivers of digestive system tumorigenesis and novel targeted therapeutics.The checkpoint kinase 2(Chk2)regulates cell-cycle progression,and Chk2 dysregulation or Chk2 mutations can lead to the development of various cancers,which makes Chk2 an important research topic.This review summarizes the roles of Chk2 in DNA-damage responses,cell-cycle regulation,autophagy,and homeostasis maintenance.We describe relationships between tumorigenesis and cell-cycle dysregulation induced by Chk2 mutations.In addition,we summarize evidence indicating that Chk2 can serve as a novel therapeutic target,based on its contributions to radiochemotherapy-resistance reversion and progress made in developing antitumor agents against Chk2.The prevailing evidence supports the conclusion that further research on Chk2 will provide a deeper understanding of digestive-system tumorigenesis and should suggest novel therapeutic targets.
基金supported by National Key Research and Development Program of China(No.2021YFB3800800 to D.C.and L.T)the National Natural Science Foundation of China(No.82030067,82250710174,82161160342,82060406,82360429 and 82172397 to D.C.and L.T.and Y.C.)+2 种基金the Hong Kong RGC(China)(No.HKU-17101821 to W.W.L and D.C.)Shenzhen Science and Technology Program(Guangdong,China)(No.JSGGKQTD20210831174330015 to H.P.and D.C.)Natural Science Foundation of Guangxi(No.2022JJA141126 to Y.C.).
文摘Osteoarthritis (OA) is a debilitating chronic joint disease affecting large populations of patients, especially the elderly. The pathological mechanisms of OA are currently unknown. Multiple risk factors are involved in OA development. Among these risk factors, alterations of mechanical loading in the joint leading to changes in biological signaling pathways have been known as a key event in OA development. The importance of AMPK-β-catenin-Runx2 signaling in the initiation and progression of OA has been recognized in recent years. In this review, we discuss the recent progress in understanding the role of this signaling pathway and the underlying interaction mechanisms during OA development. We also discuss the drug development aiming to target this signaling pathway for OA treatment.
文摘In precision cancer therapy,addressing intra-tumor heterogeneity poses a significant obstacle.Due to the heterogeneity of each cell subtype and between cells within the tumor,the sensitivity and resistance of different patients to targeted drugs,chemotherapy,etc.,are inconsistent.Concerning a specific tumor type,many feasible treatments or combinations can be used by specifically targeting the tumor microenvironment.To solve this problem,it is necessary to further study the tumor microenvironment.Single-cell sequencing techniques can dissect distinct tumor cell populations by isolating cells and using statistical computational methods.This technology may assist in the selection of targeted combination therapy,and the obtained cell subset information is crucial for the rational application of targeted therapy.In this review,we summarized the research and application advances of single-cell sequencing technology in the tumor microenvironment,including the most commonly used single-cell genomic and transcriptomic sequencing,and their future development direction was proposed.The application of single-cell sequencing technology has been expanded to include epigenomics,proteomics,metabolomics,and microbiome analysis.The integration of these different omics approaches has significantly advanced the development of single-cell multiomics sequencing technology.This innovative approach holds immense potential for various fields,such as biological research and medical investigations.Finally,we discussed the advantages and disadvantages of using single-cell sequencing to explore the tumor microenvironment.
基金supported by the National Natural Science Foundation of China(No.31970559,82171851,32370652).
文摘It is estimated that infertility impacts 8%-12%of reproductive-aged couples worldwide.Female infertility accounts for 37%of causes among infertile couples,and ovulatory dysfunction is regarded as its most common factor.1 cUL4B belongs to the Cullin family,whose members are the scaffolding proteins of Cullin-RING E3 ligases(CRLs).Human CUL4B gene mutations result in X-linked mental retardation syndromes.In addition to mental retardation,patients have symptoms such as short stature,obesity,and hypogonadism.
基金supported by the Guangzhou basic and applied basic research project(China)(No.2023A04J2337).
文摘Nowadays,although the treatment and diagnostic approaches have been improved,lung adenocarcinoma(LUAD)is still the leading cause of cancer-related death in the world with overall survival of less than five yearsi.Diagnosis of LUAD in the early stage is still a challenge,resulting from that early symptoms are not obvious2,which leads to the fact that most patients eventually die from cancer progression and chemotherapy resistance.LUAD is reported to be associated with the MAPK pathway,however,the mechanism at the cellular and genetic levels has not been clearly elucidated.Therefore,functional exploration of LUAD-and MAPK pathway-related genes is essential for understanding the pathogenesis of LUAD and exploring therapeutic measures.Figure S1 illustrates the flowchart of this study.
基金supported by the National Natural Science Foundation of China(No.81972909,31971151)the National Key Research and Development Program of China(No.2021YFC2700200)the Bio-ID Center at SJTU,and the K.C.Wong Education Foundation(H.K.).
文摘Germ cell arrest is one kind of important disease in nonobstructive azoospermia(NOA)including spermatogonia arrest,spermatocyte arrest,and round spermatid arrest.1 There is an urgent need to explore the molecular mechanisms underlying germ cell arrest,which are essentially unknown and could provide not only a promising approach for therapy but also novel possibilities for developing male contraceptives.
基金funded by grants from the Beijing Municipal Science&TechnologyCommission(China)(No.Z211100002921005 to W.W.)National High-Level Hospital Clinical Research Funding(China)(No.2022-NHLHCRF-PY-12 to W.W.)+2 种基金Hubei Provincial Department of Education's Scientific and Technological Research Project(China)(No.Q20211207 to Y.L.)Yichang Medical and Health Science and Technology Project(Hubei,China)(No.A22-2-069 to Y.L.)the Open Foundation of Hubei Province Key Laboratory of Tumor Microenvironment and Immunotherapy(China)(No.2023KZL08 to Y.L.).
文摘Krabbe disease,also known as globoid cell leukodystrophy,is a rare lysosomal storage disorder.It is primarily caused by mutations in the GALC gene on chromosome 14q31,leading to GALC enzyme deficiency in lysosomes.This results in the accumulation of toxic substrate psychosine in the nervous systems.1 Currently,hematopoietic stem cell transplantation is the only available treatment,offering only a delay in neurological deterioration.Gene therapy,particularly using recombinant adeno-associated viruses(AAVs),shows promise for treating genetic diseases by introducing functional genes into target cells.
基金funded by the National Science Foundation of China(No.82170716,81870333,82100821)the Key Laboratory Construction Plan Project of Shanxi Provincial Health Commission(China)(No.2020SYS01)+1 种基金the Key Project of Shanxi Provincial Health Commission(China)(No.2020XM21)the Key Research and Development Project of Shanxi Province,China(No.201903D321086).
文摘In recent years,molecular diagnostics has become pivotal in the detection of polycystic kidney disease(PKD).1 Nevertheless,given the extensive genomic architecture,allelic heterogeneity,and dispersed mutations in affiliated genes,the translation of its clinical prospects is constrained.2 Moreover,summarizing the pertinent literature within the past decade reveals that the majority of studies predominantly focus on three main genes(PKD1,PKD2,and PKHD1),resulting in a limited scope of genes considered(Table S1).In the present investigation,endeavoring to supersede the limitations of traditional genetic diagnosis methods,we employed next-generation sequencing to meticulously interrogate the entire coding domains and exon-intron junctions of 15 pre-eminent genes(Table S2).
基金supported by the Establishment of Sino-Austria“Belt and Road”Joint Laboratory on Traditional Chinese Medicine for Severe Infectious Diseases and Joint Research(No.2020YFE0205100)the National Key Research and Development Program of China(No.2020YFA0908000)+8 种基金the Innovation Team and Talents Cultivation Program of the National Administration of Traditional Chinese Medicine(China)(No.ZYYCXTD-C-202002)the National Natural Science Foundation of China(No.82074098,81841001)the Fundamental ResearchFunds for the Central Public Welfare Research Institutes(China)(No.ZZ13-ZD-07,ZXKT18003,ZZ14-YQ-050,ZZ14-ND-010,ZZ15-ND-10,ZZ14-FL-002,ZZ14-YQ059,ZZ15-YQ-063)Shenzhen Science and Technology Innovation Commission(Guangdong,China)(No.JCYJ20210324115800001 and JCYJ20210324114014039)the National Key R&D Program of China Key projects for international cooperation on science,technology and innovation(No.2020YFE0205100)the Shenzhen Medical Research Fund of Shenzhen Medical Academy of Research and Translation(Guangdong,China)(No.B2302051)the Distinguished Expert Project of Sichuan Province Tianfu Scholar(China)(No.CW202002)China Academy of Chinese MedicalSciencess(CACMS)InnovationFund(No.CI2023E002)State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs.
文摘Sepsis,a life-threatening condition triggered by a dysregulated host response to infection,remains a major challenge for therapeutic intervention.Despite the growing interest in immunomodulatory strategies for sepsis treatment,the effects and mechanisms of these approaches on the organ-specific inflammatory and immunosuppressive states induced by sepsis are poorly understood.According to existing studies,capsaicin(CPS)has pharmacological effects such as analgesic,antipruritic,hypolipidemia,hypoglycemia,anti-inflammatory and antibacterial,and antitumor activity.1 However,the effectiveness of CPs in treating sepsis is still unknown.
