Colorectal cancer (CRC) is one of the main reasons of tumor-related deaths worldwide.At present,the main treatment is surgery,but the results are unsatisfactory,and the prognosis is poor.The majority of patients die d...Colorectal cancer (CRC) is one of the main reasons of tumor-related deaths worldwide.At present,the main treatment is surgery,but the results are unsatisfactory,and the prognosis is poor.The majority of patients die due to liver or lung metastasis or recurrence.In recent years,great progress has been made in the field of tumor gene therapy,providing a new treatment for combating CRC.As oncolytic viruses selectively replicate almost exclusively in the cytoplasm of tumor cells and do not require integration into the host genome,they are safer,more effective and more attractive as oncolytic agents.Newcastle disease virus (NDV) is a natural RNA oncolytic virus.After NDV selectively infects tumor cells,the immune response induced by NDV’s envelope protein and intracellular factors can effectively kill the tumor without affecting normal cells.Reverse genetic techniques make NDV a vector for gene therapy.Arming the virus by inserting various exogenous genes or using NDV in combination with immunotherapy can also improve the anti-CRC capacity of NDV,and good results have been achieved in animal models and clinical treatment trials.This article reviews the molecular biological characteristics and oncolytic mechanism of NDV and discusses in vitro and in vivo experiments on NDV anti-CRC capacity and clinical treatment.In conclusion,NDV is an excellent candidate for cancer treatment,but more preclinical studies and clinical trials are needed to ensure its safety and efficacy.展开更多
Canine parvovirus type 2(CPV-2) infection is the most lethal disease of dogs with higher mortality in puppies worldwide.In today’s world,dogs are an integral part of our communities as well as dogs breeding and reari...Canine parvovirus type 2(CPV-2) infection is the most lethal disease of dogs with higher mortality in puppies worldwide.In today’s world,dogs are an integral part of our communities as well as dogs breeding and rearing has become a lucrative business.Therefore,a fast,accurate,portable,and costeffective CPV-2 detection method with the ability for on-site detection is highly desired.In this study,we for the first time proposed a nanosystem for CPV-2 DNA detection with RNA-guided RNA endonuclease Cas13 a,which upon activation results in collateral RNA degradation.We expressed LwCasl3 a in prokaryotic expression system and purified it through nickel column.Activity of Cas13 a was verified by RNA-bound fluorescent group while using a quenched fluorescent probe as signals.Further Cas13 a was combined with Recombinase polymerase amplification(RPA) and T7 transcription to establish molecular detection system termed specific high-sensitivity enzymatic reporter un-locking(SHERLOCK) for sensitive detection of CPV-2 DNA.This nanosystem can detect 100 amol/L CPV-2 DNA within 30 min.The proposed nanosystem exhibited high specificity when tested for CPV-2 and other dog viruses.This CRISPR-Cas13 a mediated sensitive detection approach can be of formidable advantage during CPV-2 outbreaks because it is time-efficient,less laborious and does not involve the use of sophisticated instruments.展开更多
Although great achievements have been made in the past decades in medicine,cancer remains a worldwide public health issue.Surgery is usually accompanied by shortcomings such as residual lesions and poor treatment effe...Although great achievements have been made in the past decades in medicine,cancer remains a worldwide public health issue.Surgery is usually accompanied by shortcomings such as residual lesions and poor treatment effects,and the successive appearance of other treatment methods,such as radiotherapy and chemotherapy,has not changed the postoperative recurrence rate,toxicity,and side effects.However,the advent of photodynamic therapy has greatly improved this situation.Photodynamic therapy is an emerging tumor diagnosis and treatment technology with good application prospects,photodynamic therapy uses a specific wavelength of light to excite a photosensitizer to generate reactive oxygen species,damage tumor blood vessels and promote tumor cell apoptosis,exerting an anti-tumor effect.Photodynamic therapy has become a new clinical anti-tumor therapy due to its clear efficacy,few side effects,and easy use in combination with other therapies.In this review,we summarized the main mechanism,current challenges,and advancements of photodynamic therapy.展开更多
Objective: to explore the expression and clinical value of CSF2RA in pan-cancer. Methods: the data was extracted from ONCOMINE, Human Protein Atlas and Kaplan Meier-plotter. The expression level of CSF2RA on cancer ti...Objective: to explore the expression and clinical value of CSF2RA in pan-cancer. Methods: the data was extracted from ONCOMINE, Human Protein Atlas and Kaplan Meier-plotter. The expression level of CSF2RA on cancer tissues and normal tissues, the relationship between CSF2RA and overall survival of cancer patients were analyzed, respectively. Results: CSF2RA mRNA was over-expressed on breast cancer, colorectal cancer, kidney cancer and liver cancer, and CSF2RA protein was over-expressed on melanoma. The expression level of CSF2RA was not associated with overall survival of cancer patients significantly. Conclusion: CSF2RA is over-expression on certain cancers and most immune cells, which maybe contributes to activation of immune system. The high expression of CSF2RA protein on melanoma is maybe associated with adverse outcome of application of GM-CSF.展开更多
The immune response after implantation is a primary determinant of the tissue-repair effects of threedimensional(3D)-printed scaffolds.Thus,scaffolds that can subtly regulate immune responses may display extraordinary...The immune response after implantation is a primary determinant of the tissue-repair effects of threedimensional(3D)-printed scaffolds.Thus,scaffolds that can subtly regulate immune responses may display extraordinary functions.Inspired by the angiogenesis promotion effect of humoral immune response,we covalently combined mesoporous silica micro rod(MSR)/polyethyleneimine(PEI)/ovalbumin(OVA)self-assembled vaccines with 3D-printed calcium phosphate cement(CPC)scaffolds for local antigen-specific immune response activation.With the response activated,antigen-specific CD4+T helper2(Th2)cells can be recruited to promote early angiogenesis.The silicon(Si)ions from MSRs can accelerate osteogenesis,with an adequate blood supply being provided.At room temperature,scaffolds with uniformly interconnected macropores were printed using a self-setting CPC-based printing paste,which promoted the uniform dispersion and structural preservation of functional polysaccharides oxidized hyaluronic acid(OHA)inside.Sustained release of OVA was achieved with MSR/PEI covalently attached to scaffolds rich in aldehyde groups as the vaccine carrier.The vaccine-loaded scaffolds effectively recruited and activated dendritic cells(DCs)for antigen presentation and promoted the osteogenic differentiation of bone marrow mesenchymal stem cells(BMSCs)in vitro.When embedded subcutaneously in vivo,the vaccine-loaded scaffolds increased the proportion of Th2 cells in the spleen and locally recruited antigenspecific T cells to promote angiogenesis in and around the scaffold.Furthermore,the result in a rat skull defect-repair model indicated that the antigen-specific vaccine-loaded scaffolds promoted the regeneration of vascularized bone.This method may provide a novel concept for patient-specific implant design for angiogenesis promotion.展开更多
A simple visual method for DNA detection during the formation of gold nanoparticles(AuNPs) was developed based on different electrostatic properties of single strand DNA(ssDNA) and double strand DNA(dsDNA).Since the s...A simple visual method for DNA detection during the formation of gold nanoparticles(AuNPs) was developed based on different electrostatic properties of single strand DNA(ssDNA) and double strand DNA(dsDNA).Since the ssDNA is easy to bind to AuNPs due to its exposed bases which could prevent saltinduced aggregation of AuNPs.The dsDNA always present negative charge because its negatively charged phosphate backbone is exposed.In this case,the dsDNA could disturb the adsorption between dsDNA and AuNPs and result in non-aggregation of AuNPs.After hybridization,chloroauric acid and ascorbic acid were added to the mixture solution,and the solution changed to red immediately and turned to purple in10 min in the present of target DNA.TEM results confirmed that the change of color stemed from aggregation of AuNPs.In order to obtain accurate results by naked eye,the DNA detection assay should be conducted under pH 7.0.展开更多
Starvation therapy has been proposed as a new anti-cancer therapy that can starve tumor cells and inhibit tumor growth by limiting the supply of nutrition or varying metabolic pathways. This approach has ignited consi...Starvation therapy has been proposed as a new anti-cancer therapy that can starve tumor cells and inhibit tumor growth by limiting the supply of nutrition or varying metabolic pathways. This approach has ignited considerable interest in medical and scientific communities due to its unparalleled safety. Of note, with the progress made in nano - medicine and nanotechnology, recent state-of-the-art studies have focused on designing smart and precise nanoplatforms capable of realizing and monitoring tumor starvation therapy and establishing starvation therapy-based synergistic strategies. These will be discussed in this review. Moreover, the potential challenges with regard to starvation therapy are also described, aiming to advance the development of starvation therapy in both the clinical and basic research areas.展开更多
Hepatocellular carcinoma(HCC)is a significant global health issue,ranking as the sixth most prevalent malignancy and the fourth leading cause of cancer-related mortality worldwide.Despite advancements in therapeutic s...Hepatocellular carcinoma(HCC)is a significant global health issue,ranking as the sixth most prevalent malignancy and the fourth leading cause of cancer-related mortality worldwide.Despite advancements in therapeutic strategies,mortality rates for HCC remain high.The tumor immune microenvironment(TIME)plays a vital role in HCC progression by influencing tumor cell survival and growth.Recent studies highlight the essential role of exosomes in mediating intercellular communication within the TIME,particularly in interactions among tumor cells,immune cells,and fibroblasts.These interactions drive critical aspects of tumor development,including immune escape,angiogenesis,drug resistance,and metastasis.A detailed understanding of the molecular mechanisms by which exosomes modulate the TIME is essential for developing targeted therapies.This review systematically evaluated the roles and regulatory mechanisms of exosomes within the TIME of HCC,examining the impact of both HCC-derived and non-HCC-derived exosomes on various cellular components within the TIME.It emphasized their regulatory effects on cell phenotypes and functions,as well as their roles in HCC progression.The review also explored the potential applications of exosome-based immunotherapies,offering new insights into improving therapeutic strategies for HCC.展开更多
Hepatocellular carcinoma(HCC)is one of the deadliest malignant tumors in the world,and its incidence and mortality have increased year by year.HCC research has increasingly focused on understanding its pathogenesis an...Hepatocellular carcinoma(HCC)is one of the deadliest malignant tumors in the world,and its incidence and mortality have increased year by year.HCC research has increasingly focused on understanding its pathogenesis and developing treatments.The Wnt signaling pathway,a complex and evolutionarily conserved signal transduction system,has been extensively studied in the genesis and treatment of several malignant tumors.Recent investigations suggest that the pathogenesis of HCC may be significantly influenced by dysregulated Wnt/β-catenin signaling.This article aimed to examine the pathway that controls Wnt signaling in HCC and its mechanisms.In addition,we highlighted the role of this pathway in HCC etiology and targeted treatment.展开更多
Pharmacogenomic landscapes and related databases are important for identifying the biomarkers of drug response and toxicity.However,these data are still lacking for the Chinese population.In this study,we constructed ...Pharmacogenomic landscapes and related databases are important for identifying the biomarkers of drug response and toxicity.However,these data are still lacking for the Chinese population.In this study,we constructed a pharmacogenomic landscape and an associated database using whole-genome sequencing data generated by non-invasive prenatal testing in 206,640 Chinese individuals.In total,1,577,513 variants(including 331,610 novel variants)were identified among 3,538 pharmacogenes related to 2,086 drugs.We found that the variant spectrum in the Chinese population differed among the seven major regions.Regional differences also exist among provinces in China.The average numbers of drug enzyme,transporter,and receptor variants were 258,557,and 632,respectively.Subsequent correlation analysis indicated that the pharmacogenes affecting multiple drugs had fewer variants.Among the 16 categories of drugs,we found that nervous system,cardiovascular system,and genitourinary system/sex hormone drugs were more likely to be affected by variants of pharmacogenes.Characteristics of the variants in the enzyme,transporter,and receptor subfamilies showed specificity.To explore the clinical utility of these data,a genetic association study was conducted on 1,019 lung cancer patients.Two novel variants,AKT2 chr19:40770621 C>G and SLC19A1 chr21:46934171 A>C,were identified as novel platinum response biomarkers.Finally,a pharmacogenomic database,named the Chinese Pharmacogenomic Knowledge Base(CNPKB:http://www.cnpkb.com.cn/),was constructed to collect all the data.In summary,a pharmacogenomic landscape and database for the Chinese population were constructed in this study,which could support personalized Chinese medicine in the future.展开更多
Cartilage is solid connective tissue that recovers slowly from injury,and pain and dysfunction from cartilage damage affect many people.The treatment of cartilage injury is clinically challenging and there is no optim...Cartilage is solid connective tissue that recovers slowly from injury,and pain and dysfunction from cartilage damage affect many people.The treatment of cartilage injury is clinically challenging and there is no optimal solution,which is a hot research topic at present.With the rapid development of 3D printing technology in recent years,3D bioprinting can better mimic the complex microstructure of cartilage tissue and thus enabling the anatomy and functional regeneration of damaged cartilage.This article reviews the methods of 3D printing used to mimic cartilage structures,the selection of cells and biological factors,and the development of bioinks and advances in scaffold structures,with an emphasis on how 3D printing structure provides bioactive cargos in each stage to enhance the effect.Finally,clinical applications and future development of simulated cartilage printing are introduced,which are expected to provide new insights into this field and guide other researchers who are engaged in cartilage repair.展开更多
Pancreatic cancer(PC)is an extremely aggressive cancer of the digestive system with insidious onset and the lack of effective biomarkers,resulting in late-stage diagnosis and poor prognosis.Exosomal non-coding RNAs(nc...Pancreatic cancer(PC)is an extremely aggressive cancer of the digestive system with insidious onset and the lack of effective biomarkers,resulting in late-stage diagnosis and poor prognosis.Exosomal non-coding RNAs(ncRNAs)are key mediators of intercellular communication that drive PC initiation and advancement.By modulating gene expression,they impact tumor microenvironment(TME)remodeling,proliferation,migration,apoptosis,and immune evasion.Critically,exosomal ncRNAs serve as promising biomarkers for early diagnosis and prognostic assessment.This review summarizes the current research achievements regarding exosomal ncRNAs in PC,systematically elaborating on their roles in tumor occurrence,metastasis,chemoresistance and the TME.Furthermore,by integrating the potential of exosomal ncRNAs in the diagnosis,treatment and prognosis of PC and by highlighting the challenges and future directions,this review aims to offer novel insights for future research and clinical translation of exosomal ncRNAs in PC.展开更多
Background:Chemoresistance is a major cause of treatment failure in gas-tric cancer(GC).Heterogeneous nuclear ribonucleoprotein A2B1(hnRNPA2B1)is an N6-methyladenosine(m^(6)A)-binding protein involved in a variety of ...Background:Chemoresistance is a major cause of treatment failure in gas-tric cancer(GC).Heterogeneous nuclear ribonucleoprotein A2B1(hnRNPA2B1)is an N6-methyladenosine(m^(6)A)-binding protein involved in a variety of can-cers.However,whether m^(6)A modification and hnRNPA2B1 play a role in GC chemoresistance is largely unknown.In this study,we aimed to investigate the role of hnRNPA2B1 and the downstream mechanism in GC chemoresistance.Methods:The expression of hnRNPA2B1 among public datasets were analyzed and validated by quantitative PCR(qPCR),Western blotting,immunoflu-orescence,and immunohistochemical staining.The biological functions of hnRNPA2B1 in GC chemoresistance were investigated both in vitro and in vivo.RNA sequencing,methylated RNA immunoprecipitation,RNA immunoprecipi-tation,and RNA stability assay were performed to assess the association between hnRNPA2B1 and the binding RNA.The role of hnRNPA2B1 in maintenance of GC stemness was evaluated by bioinformatic analysis,qPCR,Western blotting,immunofluorescence,and sphere formation assays.The expression patterns of hnRNPA2B1 and downstream regulators in GC specimens from patients who received adjuvant chemotherapy were analyzed by RNAscope and multiplex immunohistochemistry.Results:Elevated expression of hnRNPA2B1 was found in GC cells and tis-sues,especially in multidrug-resistant(MDR)GC cell lines.The expression of hnRNPA2B1 was associated with poor outcomes of GC patients,especially in those who received 5-fluorouracil treatment.Silencing hnRNPA2B1 effectively sensitized GC cells to chemotherapy by inhibiting cell proliferation and induc-ing apoptosis both in vitro and in vivo.Mechanically,hnRNPA2B1 interacted with and stabilized long noncoding RNA NEAT1 in an m^(6)A-dependent man-ner.Furthermore,hnRNPA2B1 and NEAT1 worked together to enhance the stemness properties of GC cells via Wnt/β-catenin signaling pathway.In clin-ical specimens from GC patients subjected to chemotherapy,the expression levels of hnRNPA2B1,NEAT1,CD133,and CD44 were markedly elevated in non-responders compared with responders.Conclusion:Our findings indicated that hnRNPA2B1 interacts with and stabi-lizes lncRNA NEAT1,which contribute to the maintenance of stemness property via Wnt/β-catenin pathway and exacerbate chemoresistance in GC.展开更多
To the Editor:Probiotics are a promising treatment modality for functional constipation(FC);however,the factors affecting individual responses to probiotics remain unclear.Growing evidence has identified that there is...To the Editor:Probiotics are a promising treatment modality for functional constipation(FC);however,the factors affecting individual responses to probiotics remain unclear.Growing evidence has identified that there is a strong relationship among the gut microbiota and constipation and related gut-brain axis.[1]The gut microbiota may modulate the gut functions via gut metabolites or trigger the release of gut hormones,such as peptide YY,gastric inhibitory polypeptide,and 5-hydroxytryptamine.[2]In turn,gut hormones affect gut secretion,motility,and sensation through their receptors located on epithelial,enteric,and smooth muscle cells.[2]Based on these findings,exogenous probiotics have been used in patients with constipation;however,few have produced consistent results.[3]In this study,we investigated the efficacy and safety of several specific probiotics strains for constipation,and also examined the potential reasons for the individualized effects of probiotics,which may facilitate interventional decisionmaking for FC patients.展开更多
Procalcitonin(PCT)serves as a crucial biomarker utilized in diverse clinical contexts,including sepsis diagnosis and emergency departments.Its applications extend to identifying pathogens,assessing infection severity,...Procalcitonin(PCT)serves as a crucial biomarker utilized in diverse clinical contexts,including sepsis diagnosis and emergency departments.Its applications extend to identifying pathogens,assessing infection severity,guiding drug administration,and implementing theranostic strategies.However,current clinical deployed methods cannot meet the needs for accurate or real-time quantitative monitoring of PCT.This review aims to introduce these emerging PCT immunoassay technologies,focusing on analyzing their advantages in improving detection performances,such as easy operation and high precision.The fundamental principles and characteristics of state-of-the-art methods are first introduced,including chemiluminescence,immunofluorescence,latex-enhanced turbidity,enzyme-linked immunosorbent,colloidal gold immunochromatography,and radioimmunoassay.Then,improved methods using new materials and new technologies are briefly described,for instance,the combination with responsive nanomaterials,Raman spectroscopy,and digital microfluidics.Finally,the detection performance parameters of these methods and the clinical importance of PCT detection are also discussed.展开更多
Sepsis is a leading cause of death worldwide.This syndrome is commonly accompanied by overactivation of coagulation,excessive reactive oxygen species(ROS),and inflammatory cytokine storm.Notably,disseminated intravasc...Sepsis is a leading cause of death worldwide.This syndrome is commonly accompanied by overactivation of coagulation,excessive reactive oxygen species(ROS),and inflammatory cytokine storm.Notably,disseminated intravascular coagulation(DIC)accounts for around 40%of sepsis-associated deaths.However,anticoagulant therapy is still difficult for sepsis treatment because of the lethal bleeding side effects.Although the relationship between ROS and inflammatory cytokine storm has been described clearly,the pathogenic role of ROS in DIC,however,is still unclear,which renders novel therapeutic approaches hard to achieve bedside for inhibiting DIC.Herein,our new finding reveals that ROS greatly facilitates the entry of lipopolysaccharide(LPS)into the macrophage cytoplasm,which subsequently activates the caspase-11/gasdermin D pathway,and finally induces DIC through phosphatidylserine exposure.Based on this finding,novel gallic acid-modified Mo-based polyoxometalate dots(M-dots)with outstanding antioxidant activity are developed to provide ideal and efficient inhibition of DIC.As expected,M-dots are capable of markedly inhibiting sepsis-caused coagulation,organ injury,and death in sepsis.This therapeutic strategy,blocking the upstream pathway of coagulation rather than coagulation itself,can avoid the side effects of extensive bleeding caused by conventional anticoagulation therapy,and will provide a new avenue for the efficient treatment of sepsis.展开更多
Neuropilins(NRP1 and NRP2)are multifunctional receptor proteins that are involved in nerve,blood vessel,and tumor development.NRP1 was first found to be expressed in neurons,but subsequent studies have demonstrated it...Neuropilins(NRP1 and NRP2)are multifunctional receptor proteins that are involved in nerve,blood vessel,and tumor development.NRP1 was first found to be expressed in neurons,but subsequent studies have demonstrated its surface expression in cells from the endothelium and lymph nodes.NRP1 has been demonstrated to be involved in the occurrence and development of a variety of cancers.NRP1 interacts with various cytokines,such as vascular endothelial growth factor family and its receptor and transforming growth factor p i and its receptor,to affect tumor angiogenesis,tumor proliferation,and migration.In addition,NRP1+regulatory T cells(Tregs)play an inhibitory role in tumor immunity.High numbers of NRP1+Tregs were associated with cancer prognosis.Targeting NRP1 has shown promise,and antagonists against NRP1 have had therapeutic efficacy in preliminary clinical studies.NRP1 treatment modalities using nanomaterials,targeted drugs,oncolytic viruses,and radio-chemotherapy have gradually been developed.Hence,we reviewed the use of NRP1 in the context of tumorigenesis,progression,and treatment.展开更多
The signal adaptor myeloid differentiation primary response 88(MyD88)of Toll-like receptor(TLR)signaling is universally expressed in immune cells and non-immune cells,and myeloid cells play a significant role in modul...The signal adaptor myeloid differentiation primary response 88(MyD88)of Toll-like receptor(TLR)signaling is universally expressed in immune cells and non-immune cells,and myeloid cells play a significant role in modulating colitis.Macrophages are myeloid lineage cells which is important for maintaining intestinal homeostasis in inflammation.1 And macrophages can recognize invading pathogens through pattern recognition receptors(PRRs),such as TLRs and the nucleotide oligomerization domain(NOD)-like receptor family,pyrin domain-containing 3(NLRP3),and quickly infiltrate the injured site leading to inflammation.2 MyD88 expression in myeloid cells can rescue the intestinal injury induced by dextran sulfate sodium(DSS)in murine models.However,the mechanism whereby MyD88 works in myeloid cells and influence the progress of the disease remain elusive.In this study,we used DSS induced colitis mouse model and found Lysm-cre-MyD88fl/fl(MyD88ΔМΦ)mice were more susceptible to colitis.The deficiency of MyD88 leads to up-regulation of S100A8,which activate NLRP3 inflammasome and their associated pyroptosis in intestinal epithelial cells in a RAGE dependent manner.Thus,MyD88 signaling in macrophages,which is necessary to maintain intestinal homeostasis,crucially prevents the development of colitis.Our results may shed new lights on potential targets that can be applied in colitis therapy.展开更多
Oncolytic viruses(OVs)as one promising antitumor methods have made important contributions to tumor immunotherapy,which arouse increasing attention.They provide the dual mechanisms including direct killing effect towa...Oncolytic viruses(OVs)as one promising antitumor methods have made important contributions to tumor immunotherapy,which arouse increasing attention.They provide the dual mechanisms including direct killing effect toward tumor cells and immune activation for elevating antitumor responses,which have been proved in many preclinical studies.Especially,natural or genetically modified viruses as clinical immune preparations have emerged as a new promising approach objective to oncology treatment.The approval of talimogene laherparepvec(T-VEC)by the U.S.Food and Drug Administration(FDA)for the therapy of advanced melanoma could be considered as a milestone achievement in the clinical translation of OV.In this review,we first discussed the antitumor mechanisms of OVs with an emphasis on targeting,replication,and propagation.We further outlined the state of the art of current OVs in tumor and underlined the activated biological effects especially including immunity.More significantly,the enhanced immune responses based on OVs were systematically discussed from different perspectives such as combination with immunotherapy,genetic engineering of OVs,integration with nanobiotechnology or nanoparticles,and antiviral response counteraction,where their principles were shed light on.The development of OVs in the clinics was also highlighted to analyze the actuality and concerns of different OV applications in clinical trials.At last,the future perspectives and challenges of OVs as an already widely accepted treatment means were discussed.This review will provide a systematic review and deep insight into OV development and also offer new opportunities and guidance pathways to drive the further clinical translation.展开更多
Current approaches for the treatment of chronic lymphocytic leukemia （CLL） have greatly improved the prognosis for survival, but some patients remain refractive to these therapeutic regimens. Hence, in addition to r...Current approaches for the treatment of chronic lymphocytic leukemia （CLL） have greatly improved the prognosis for survival, but some patients remain refractive to these therapeutic regimens. Hence, in addition to reducing the long-term side- effects of therapeutics for all leukemia patients, there is an urgent need for novel therapeutic strategies for difficult-to-treat leukemia cases. Due to the cytotoxicity of drugs, the major challenge currently is to deliver the therapeutic agents to neoplastic cells while preserving the viability of non-malignant ceils. In this study, we propose a therapeutic approach in which high doses of hydroxychloroquine and chlorambucil were loaded into biodegradable polymeric nanopartides coated with an anti-CD20 antibody.We first demonstrated the ability of the nanoparticles to target and internalize in tumor B-cells. Moreover, these nanoparticles could kill not only p53-mutated]deleted leukemia cells expressing a low amount of CD20, but also circulating primary ceils isolated from chronic lymphocytic leukemia patients. The safety of these nanoparticles was also demonstrated in healthy mice, and their therapeutic effects were shown in a new model of aggressive leukemia. These results showed that anti-CD20 nanoparticles containing hydroxychloroquine and chlorambucil can be effective in controlling aggressive leukemia and provided a rationale for adopting this approach for the treatment of other B-cell disorders.展开更多
文摘Colorectal cancer (CRC) is one of the main reasons of tumor-related deaths worldwide.At present,the main treatment is surgery,but the results are unsatisfactory,and the prognosis is poor.The majority of patients die due to liver or lung metastasis or recurrence.In recent years,great progress has been made in the field of tumor gene therapy,providing a new treatment for combating CRC.As oncolytic viruses selectively replicate almost exclusively in the cytoplasm of tumor cells and do not require integration into the host genome,they are safer,more effective and more attractive as oncolytic agents.Newcastle disease virus (NDV) is a natural RNA oncolytic virus.After NDV selectively infects tumor cells,the immune response induced by NDV’s envelope protein and intracellular factors can effectively kill the tumor without affecting normal cells.Reverse genetic techniques make NDV a vector for gene therapy.Arming the virus by inserting various exogenous genes or using NDV in combination with immunotherapy can also improve the anti-CRC capacity of NDV,and good results have been achieved in animal models and clinical treatment trials.This article reviews the molecular biological characteristics and oncolytic mechanism of NDV and discusses in vitro and in vivo experiments on NDV anti-CRC capacity and clinical treatment.In conclusion,NDV is an excellent candidate for cancer treatment,but more preclinical studies and clinical trials are needed to ensure its safety and efficacy.
基金supported by the National Key Research and Development Program of China (No.2017YFA0205301)National Natural Science Foundation of China (Nos.81902153,61527806 and 81430055)+2 种基金Key Research and Development Project of Jiangsu Province (No.BE2019761)Programs for Changjiang Scholars and Innovative Research Team in University (No.IRT_15R13)open Funding of State Key Laboratory of Oral Diseases (No.SKLOD20190F03)
文摘Canine parvovirus type 2(CPV-2) infection is the most lethal disease of dogs with higher mortality in puppies worldwide.In today’s world,dogs are an integral part of our communities as well as dogs breeding and rearing has become a lucrative business.Therefore,a fast,accurate,portable,and costeffective CPV-2 detection method with the ability for on-site detection is highly desired.In this study,we for the first time proposed a nanosystem for CPV-2 DNA detection with RNA-guided RNA endonuclease Cas13 a,which upon activation results in collateral RNA degradation.We expressed LwCasl3 a in prokaryotic expression system and purified it through nickel column.Activity of Cas13 a was verified by RNA-bound fluorescent group while using a quenched fluorescent probe as signals.Further Cas13 a was combined with Recombinase polymerase amplification(RPA) and T7 transcription to establish molecular detection system termed specific high-sensitivity enzymatic reporter un-locking(SHERLOCK) for sensitive detection of CPV-2 DNA.This nanosystem can detect 100 amol/L CPV-2 DNA within 30 min.The proposed nanosystem exhibited high specificity when tested for CPV-2 and other dog viruses.This CRISPR-Cas13 a mediated sensitive detection approach can be of formidable advantage during CPV-2 outbreaks because it is time-efficient,less laborious and does not involve the use of sophisticated instruments.
基金supported by the National Natural Science Foundation of China(No.82072340)the Major National Science and Technology Projects–Major New Drug Creation(2019ZX09301-132)+1 种基金Changjiang Scholars and Innovative Research Team in University(No.IRT_15R13)Guangxi Science and Technology Base and Talent Special Project(No.AD17129003).
文摘Although great achievements have been made in the past decades in medicine,cancer remains a worldwide public health issue.Surgery is usually accompanied by shortcomings such as residual lesions and poor treatment effects,and the successive appearance of other treatment methods,such as radiotherapy and chemotherapy,has not changed the postoperative recurrence rate,toxicity,and side effects.However,the advent of photodynamic therapy has greatly improved this situation.Photodynamic therapy is an emerging tumor diagnosis and treatment technology with good application prospects,photodynamic therapy uses a specific wavelength of light to excite a photosensitizer to generate reactive oxygen species,damage tumor blood vessels and promote tumor cell apoptosis,exerting an anti-tumor effect.Photodynamic therapy has become a new clinical anti-tumor therapy due to its clear efficacy,few side effects,and easy use in combination with other therapies.In this review,we summarized the main mechanism,current challenges,and advancements of photodynamic therapy.
文摘Objective: to explore the expression and clinical value of CSF2RA in pan-cancer. Methods: the data was extracted from ONCOMINE, Human Protein Atlas and Kaplan Meier-plotter. The expression level of CSF2RA on cancer tissues and normal tissues, the relationship between CSF2RA and overall survival of cancer patients were analyzed, respectively. Results: CSF2RA mRNA was over-expressed on breast cancer, colorectal cancer, kidney cancer and liver cancer, and CSF2RA protein was over-expressed on melanoma. The expression level of CSF2RA was not associated with overall survival of cancer patients significantly. Conclusion: CSF2RA is over-expression on certain cancers and most immune cells, which maybe contributes to activation of immune system. The high expression of CSF2RA protein on melanoma is maybe associated with adverse outcome of application of GM-CSF.
基金supported by the National Key Research and Development Program of China(2019YFA0112000 and 2018YFB1105600)the National Natural Science Foundation of China(81930051)+2 种基金Shanghai Municipal Education Commission-Gaofeng Clinical Medicine Grant Support(20171906)Shanghai Jiao Tong University “Medical and Research”Program(ZH2018ZDA04)Foundation of National Facility for Translational Medicine(Shanghai)(TMSK-2020-117)。
文摘The immune response after implantation is a primary determinant of the tissue-repair effects of threedimensional(3D)-printed scaffolds.Thus,scaffolds that can subtly regulate immune responses may display extraordinary functions.Inspired by the angiogenesis promotion effect of humoral immune response,we covalently combined mesoporous silica micro rod(MSR)/polyethyleneimine(PEI)/ovalbumin(OVA)self-assembled vaccines with 3D-printed calcium phosphate cement(CPC)scaffolds for local antigen-specific immune response activation.With the response activated,antigen-specific CD4+T helper2(Th2)cells can be recruited to promote early angiogenesis.The silicon(Si)ions from MSRs can accelerate osteogenesis,with an adequate blood supply being provided.At room temperature,scaffolds with uniformly interconnected macropores were printed using a self-setting CPC-based printing paste,which promoted the uniform dispersion and structural preservation of functional polysaccharides oxidized hyaluronic acid(OHA)inside.Sustained release of OVA was achieved with MSR/PEI covalently attached to scaffolds rich in aldehyde groups as the vaccine carrier.The vaccine-loaded scaffolds effectively recruited and activated dendritic cells(DCs)for antigen presentation and promoted the osteogenic differentiation of bone marrow mesenchymal stem cells(BMSCs)in vitro.When embedded subcutaneously in vivo,the vaccine-loaded scaffolds increased the proportion of Th2 cells in the spleen and locally recruited antigenspecific T cells to promote angiogenesis in and around the scaffold.Furthermore,the result in a rat skull defect-repair model indicated that the antigen-specific vaccine-loaded scaffolds promoted the regeneration of vascularized bone.This method may provide a novel concept for patient-specific implant design for angiogenesis promotion.
基金financially supported by the National Key Research and Development Program of China (No.2017YFA0205301)the National Natural Science Foundation of China (Nos.61527806, 81902153 and 61871180)+2 种基金the Natural Science Foundation of Hunan Province (No.2017JJ2069)the Hunan Key Research Project (No.2017SK2174)the Programs for Changjiang Scholars and Innovative Research Team in University (No.IRT_15R13)
文摘A simple visual method for DNA detection during the formation of gold nanoparticles(AuNPs) was developed based on different electrostatic properties of single strand DNA(ssDNA) and double strand DNA(dsDNA).Since the ssDNA is easy to bind to AuNPs due to its exposed bases which could prevent saltinduced aggregation of AuNPs.The dsDNA always present negative charge because its negatively charged phosphate backbone is exposed.In this case,the dsDNA could disturb the adsorption between dsDNA and AuNPs and result in non-aggregation of AuNPs.After hybridization,chloroauric acid and ascorbic acid were added to the mixture solution,and the solution changed to red immediately and turned to purple in10 min in the present of target DNA.TEM results confirmed that the change of color stemed from aggregation of AuNPs.In order to obtain accurate results by naked eye,the DNA detection assay should be conducted under pH 7.0.
基金the National Natural Science Foundation of China (Grant No. 81771836,81501473)the Guangxi Collaborative Innovation Center of Biomedicine (Grant No. GCICB-SR-201703)the Fostering Project of Shanghai Municipal Commission of Health and Family Planning for Excellent Young Medical Scholars (Grant No. 2018YQ31).
文摘Starvation therapy has been proposed as a new anti-cancer therapy that can starve tumor cells and inhibit tumor growth by limiting the supply of nutrition or varying metabolic pathways. This approach has ignited considerable interest in medical and scientific communities due to its unparalleled safety. Of note, with the progress made in nano - medicine and nanotechnology, recent state-of-the-art studies have focused on designing smart and precise nanoplatforms capable of realizing and monitoring tumor starvation therapy and establishing starvation therapy-based synergistic strategies. These will be discussed in this review. Moreover, the potential challenges with regard to starvation therapy are also described, aiming to advance the development of starvation therapy in both the clinical and basic research areas.
基金supported by the National Natural Science Foundation of China(8247274382300921)+8 种基金the Beijing Xisike Clinical Oncology Research Foundation(Y-QL202201-0020)the Beijing Science and Technology Innovation Medical Development Foundation(KC2023-JX-0186-FM046)the Opening Project of Huzhou Key Laboratory of Translational Medicine(HZZHYX-2024-01)the Opening Project of the Scientific and Technological Innovation Major Base of Guangxi(2022-36-Z05-GXSWBX202201)the Key Laboratory of Clinical Laboratory Diagnosis and Translational Research of Zhejiang Province(2022E10022)the Opening Project of Fujian Provincial Key Laboratory of Tumor Biotherapy(FJZL2023001)the Opening Project of Fujian Provincial Key Laboratory of Translational Cancer Medicine(TCM2024-3)the Thematic Research Support Scheme of the State Key Laboratory of Liver Research,The University of Hong Kong(SKLLR/TRSS/2022/08)the Chen Xiaoping Foundation for the Development of Science and Technology of Hubei Province(CXPJJH123003-005).
文摘Hepatocellular carcinoma(HCC)is a significant global health issue,ranking as the sixth most prevalent malignancy and the fourth leading cause of cancer-related mortality worldwide.Despite advancements in therapeutic strategies,mortality rates for HCC remain high.The tumor immune microenvironment(TIME)plays a vital role in HCC progression by influencing tumor cell survival and growth.Recent studies highlight the essential role of exosomes in mediating intercellular communication within the TIME,particularly in interactions among tumor cells,immune cells,and fibroblasts.These interactions drive critical aspects of tumor development,including immune escape,angiogenesis,drug resistance,and metastasis.A detailed understanding of the molecular mechanisms by which exosomes modulate the TIME is essential for developing targeted therapies.This review systematically evaluated the roles and regulatory mechanisms of exosomes within the TIME of HCC,examining the impact of both HCC-derived and non-HCC-derived exosomes on various cellular components within the TIME.It emphasized their regulatory effects on cell phenotypes and functions,as well as their roles in HCC progression.The review also explored the potential applications of exosome-based immunotherapies,offering new insights into improving therapeutic strategies for HCC.
基金funded by the National Natural Science Foundation of China(8247274382300921)+11 种基金the Beijing Xisike Clinical Oncology Research Foundation(Y-QL202201-0020)the Beijing Science and Technology Innovation Medical Development Foundation(KC2023-JX-0186-FM046)the Anhui Engineering Technology Research Center of Biochemical Pharmaceutical(Bengbu Medical University)(2024SYKFD01)the Opening Project of the Scientific and Technological Innovation Major Base of Guangxi(2022-36-Z05-GXSWBX202201)the Key Laboratory of Clinical Laboratory Diagnosis and Translational Research of Zhejiang Province(2022E10022)the Opening Project of Fujian Provincial Key Laboratory of Tumor Biotherapy(FJZL2023001)the Opening Project of Fujian Provincial Key Laboratory of Translational Cancer Medicine(TCM2024-3)the Opening Project of Fujian Provincial Key Laboratory of Innovative Drug Target Research(FJ-YW-2024KF02)the Thematic Research Support Scheme of the State Key Laboratory of Liver Research,The University of Hong Kong(SKLLR/TRSS/2022/08)the Chen Xiaoping Foundation for the Development of Science and Technology of Hubei Province(CXPJJH123003-005)the Postgraduate Research&Practice Innovation Program of Harbin Medical University(YJSCX2024-110HYD)the Construction Project of Shanghai Key Laboratory of Molecular Imaging(18DZ2260400).
文摘Hepatocellular carcinoma(HCC)is one of the deadliest malignant tumors in the world,and its incidence and mortality have increased year by year.HCC research has increasingly focused on understanding its pathogenesis and developing treatments.The Wnt signaling pathway,a complex and evolutionarily conserved signal transduction system,has been extensively studied in the genesis and treatment of several malignant tumors.Recent investigations suggest that the pathogenesis of HCC may be significantly influenced by dysregulated Wnt/β-catenin signaling.This article aimed to examine the pathway that controls Wnt signaling in HCC and its mechanisms.In addition,we highlighted the role of this pathway in HCC etiology and targeted treatment.
基金supported by the National Natural Science Foundation of China(82073943,82373962,and 82450103 to J-Y.Y. and 82204533 to J.J.C.)a Scientific Research Project of the Furong Laboratory of Central South University (2023SK2083 to J-Y.Y.)+4 种基金the Natural Science Foundation of Hunan Province(2023JJ40931 to JJ.C 2023JU50251 to J.-C.W,and 2024JJ6633 to Y.W.)the Postdoctoral Fellowship Programof CPSF (GZB20240878 to Y.W.)the Hunan Innovation platform and talent program(2020RC3086 to C.-P.L)the Non-profit Central Research Institute Fund of the Chinese Academyof Medical Scienoes (2020 PT320-004to J.-G.L)the Open Fund for ScientificResearch ofNHC Key Laboratory of Personalized Diagnosis and Treatment of Nasopharyn-geal Carcinoma (2021NPCK01 to J.-Y.Y.).
文摘Pharmacogenomic landscapes and related databases are important for identifying the biomarkers of drug response and toxicity.However,these data are still lacking for the Chinese population.In this study,we constructed a pharmacogenomic landscape and an associated database using whole-genome sequencing data generated by non-invasive prenatal testing in 206,640 Chinese individuals.In total,1,577,513 variants(including 331,610 novel variants)were identified among 3,538 pharmacogenes related to 2,086 drugs.We found that the variant spectrum in the Chinese population differed among the seven major regions.Regional differences also exist among provinces in China.The average numbers of drug enzyme,transporter,and receptor variants were 258,557,and 632,respectively.Subsequent correlation analysis indicated that the pharmacogenes affecting multiple drugs had fewer variants.Among the 16 categories of drugs,we found that nervous system,cardiovascular system,and genitourinary system/sex hormone drugs were more likely to be affected by variants of pharmacogenes.Characteristics of the variants in the enzyme,transporter,and receptor subfamilies showed specificity.To explore the clinical utility of these data,a genetic association study was conducted on 1,019 lung cancer patients.Two novel variants,AKT2 chr19:40770621 C>G and SLC19A1 chr21:46934171 A>C,were identified as novel platinum response biomarkers.Finally,a pharmacogenomic database,named the Chinese Pharmacogenomic Knowledge Base(CNPKB:http://www.cnpkb.com.cn/),was constructed to collect all the data.In summary,a pharmacogenomic landscape and database for the Chinese population were constructed in this study,which could support personalized Chinese medicine in the future.
基金supported by the National Natural Science Foundation of China(Grant No.:82022033)Scientific and Technological Innovation Major Base of Guangxi(Grant No.:2022-36-Z05)the program for Shanghai Young Top-Notch Talent.
文摘Cartilage is solid connective tissue that recovers slowly from injury,and pain and dysfunction from cartilage damage affect many people.The treatment of cartilage injury is clinically challenging and there is no optimal solution,which is a hot research topic at present.With the rapid development of 3D printing technology in recent years,3D bioprinting can better mimic the complex microstructure of cartilage tissue and thus enabling the anatomy and functional regeneration of damaged cartilage.This article reviews the methods of 3D printing used to mimic cartilage structures,the selection of cells and biological factors,and the development of bioinks and advances in scaffold structures,with an emphasis on how 3D printing structure provides bioactive cargos in each stage to enhance the effect.Finally,clinical applications and future development of simulated cartilage printing are introduced,which are expected to provide new insights into this field and guide other researchers who are engaged in cartilage repair.
基金This research was funded by National Natural Science Foundation of China(82472743,82300921,82270599)Natural Science Foundation of Heilongjiang Province(LH2023H043)+11 种基金Key R&D Program of Heilongjiang Province(GZ2024023)Beijing XisikeClinicalOncology Research Foundation(Y-QL202201-0020)Beijing Science and Technology InnovationMedical Development Foundation(KC2023-JX-0186-FM046)Anhui Engineering Technology Research Center of Biochemical Pharmaceutical,Bengbu Medical University(2024SYKFD01)Opening Project of the Scientific and Technological Innovation Major Base of Guangxi(2022-36-Z05-GXSWBX202201)Opening Project of Key Laboratory of Biological Molecular Medicine Research(Guangxi Medical University),Education Department of Guangxi Zhuang Autonomous Region(GXSWFZ202401)Key Laboratory of Human Development and Disease Research,GuangxiMedicalUniversity,EducationDepartment ofGuangxi ZhuangAutonomous Region(RTFY202301)Opening Project of Key Laboratory of Functional and Clinical Translational Medicine,Fujian Province University(XMMC-OP2024012)Opening Project of Fujian Provincial Key Laboratory of Tumor Biotherapy(FJZL2023001)Opening Project of Fujian Provincial Key Laboratory of Translational CancerMedicine(TCM2024-3)Opening Project of Fujian Provincial Key Laboratory of Innovative Drug Target Research(FJ-YW-2024KF02)Thematic Research Support Scheme of State Key Laboratory of Liver Re-search,The University of Hong Kong(SKLLR/TRSS/2022/08).
文摘Pancreatic cancer(PC)is an extremely aggressive cancer of the digestive system with insidious onset and the lack of effective biomarkers,resulting in late-stage diagnosis and poor prognosis.Exosomal non-coding RNAs(ncRNAs)are key mediators of intercellular communication that drive PC initiation and advancement.By modulating gene expression,they impact tumor microenvironment(TME)remodeling,proliferation,migration,apoptosis,and immune evasion.Critically,exosomal ncRNAs serve as promising biomarkers for early diagnosis and prognostic assessment.This review summarizes the current research achievements regarding exosomal ncRNAs in PC,systematically elaborating on their roles in tumor occurrence,metastasis,chemoresistance and the TME.Furthermore,by integrating the potential of exosomal ncRNAs in the diagnosis,treatment and prognosis of PC and by highlighting the challenges and future directions,this review aims to offer novel insights for future research and clinical translation of exosomal ncRNAs in PC.
基金National Natural Science Foundation of China,Grant/Award Numbers:82073197,82273142,82222058。
文摘Background:Chemoresistance is a major cause of treatment failure in gas-tric cancer(GC).Heterogeneous nuclear ribonucleoprotein A2B1(hnRNPA2B1)is an N6-methyladenosine(m^(6)A)-binding protein involved in a variety of can-cers.However,whether m^(6)A modification and hnRNPA2B1 play a role in GC chemoresistance is largely unknown.In this study,we aimed to investigate the role of hnRNPA2B1 and the downstream mechanism in GC chemoresistance.Methods:The expression of hnRNPA2B1 among public datasets were analyzed and validated by quantitative PCR(qPCR),Western blotting,immunoflu-orescence,and immunohistochemical staining.The biological functions of hnRNPA2B1 in GC chemoresistance were investigated both in vitro and in vivo.RNA sequencing,methylated RNA immunoprecipitation,RNA immunoprecipi-tation,and RNA stability assay were performed to assess the association between hnRNPA2B1 and the binding RNA.The role of hnRNPA2B1 in maintenance of GC stemness was evaluated by bioinformatic analysis,qPCR,Western blotting,immunofluorescence,and sphere formation assays.The expression patterns of hnRNPA2B1 and downstream regulators in GC specimens from patients who received adjuvant chemotherapy were analyzed by RNAscope and multiplex immunohistochemistry.Results:Elevated expression of hnRNPA2B1 was found in GC cells and tis-sues,especially in multidrug-resistant(MDR)GC cell lines.The expression of hnRNPA2B1 was associated with poor outcomes of GC patients,especially in those who received 5-fluorouracil treatment.Silencing hnRNPA2B1 effectively sensitized GC cells to chemotherapy by inhibiting cell proliferation and induc-ing apoptosis both in vitro and in vivo.Mechanically,hnRNPA2B1 interacted with and stabilized long noncoding RNA NEAT1 in an m^(6)A-dependent man-ner.Furthermore,hnRNPA2B1 and NEAT1 worked together to enhance the stemness properties of GC cells via Wnt/β-catenin signaling pathway.In clin-ical specimens from GC patients subjected to chemotherapy,the expression levels of hnRNPA2B1,NEAT1,CD133,and CD44 were markedly elevated in non-responders compared with responders.Conclusion:Our findings indicated that hnRNPA2B1 interacts with and stabi-lizes lncRNA NEAT1,which contribute to the maintenance of stemness property via Wnt/β-catenin pathway and exacerbate chemoresistance in GC.
基金National Natural Science Foundation of China(Nos.81900483 and 81730016)National Clinical Research Center for Digestive Diseases,Xi’an,China(No.2015BAI13 B07)
文摘To the Editor:Probiotics are a promising treatment modality for functional constipation(FC);however,the factors affecting individual responses to probiotics remain unclear.Growing evidence has identified that there is a strong relationship among the gut microbiota and constipation and related gut-brain axis.[1]The gut microbiota may modulate the gut functions via gut metabolites or trigger the release of gut hormones,such as peptide YY,gastric inhibitory polypeptide,and 5-hydroxytryptamine.[2]In turn,gut hormones affect gut secretion,motility,and sensation through their receptors located on epithelial,enteric,and smooth muscle cells.[2]Based on these findings,exogenous probiotics have been used in patients with constipation;however,few have produced consistent results.[3]In this study,we investigated the efficacy and safety of several specific probiotics strains for constipation,and also examined the potential reasons for the individualized effects of probiotics,which may facilitate interventional decisionmaking for FC patients.
基金supported by the National Natural Science Foundation of China(22307098)the Zhejiang Provincial Natural Science Foundation of China(LGF22C100003)+4 种基金the Wenzhou high-level innovation team(Development and application team of functional liver cancer-on-a-chip)the Wenzhou Basic Research Projects(Y2023147)the Key Projects of Wenzhou Science and Technology Bureau(ZG2023013)the program of WIUCASQD2021012 from Wenzhou Institute,University of Chinese Academy of Sciencesthe Scientific and Technological Innovation Major Base of Guangxi(No.2022-36-Z05).
文摘Procalcitonin(PCT)serves as a crucial biomarker utilized in diverse clinical contexts,including sepsis diagnosis and emergency departments.Its applications extend to identifying pathogens,assessing infection severity,guiding drug administration,and implementing theranostic strategies.However,current clinical deployed methods cannot meet the needs for accurate or real-time quantitative monitoring of PCT.This review aims to introduce these emerging PCT immunoassay technologies,focusing on analyzing their advantages in improving detection performances,such as easy operation and high precision.The fundamental principles and characteristics of state-of-the-art methods are first introduced,including chemiluminescence,immunofluorescence,latex-enhanced turbidity,enzyme-linked immunosorbent,colloidal gold immunochromatography,and radioimmunoassay.Then,improved methods using new materials and new technologies are briefly described,for instance,the combination with responsive nanomaterials,Raman spectroscopy,and digital microfluidics.Finally,the detection performance parameters of these methods and the clinical importance of PCT detection are also discussed.
基金supported by the National Natural Science Foundation of China(Nos.82373871,21974134,82072152,82270137,and 82370140)the Hunan Science Fund for Distinguished Young Scholar of China(Nos.2021JJ10067 and 2021JJ10072),the National Key Research and Development Program of China(No.2022YFC2304600)+2 种基金the Innovation-Driven Project of Central South University(No.202045005)the Hunan Provincial Natural Science Foundation of China(Nos.2022JJ30793 and 2021JJ31066)the Key Program of Ningxia Hui Autonomous Region Natural Science Foundation of China(No.2022JJ21059).
文摘Sepsis is a leading cause of death worldwide.This syndrome is commonly accompanied by overactivation of coagulation,excessive reactive oxygen species(ROS),and inflammatory cytokine storm.Notably,disseminated intravascular coagulation(DIC)accounts for around 40%of sepsis-associated deaths.However,anticoagulant therapy is still difficult for sepsis treatment because of the lethal bleeding side effects.Although the relationship between ROS and inflammatory cytokine storm has been described clearly,the pathogenic role of ROS in DIC,however,is still unclear,which renders novel therapeutic approaches hard to achieve bedside for inhibiting DIC.Herein,our new finding reveals that ROS greatly facilitates the entry of lipopolysaccharide(LPS)into the macrophage cytoplasm,which subsequently activates the caspase-11/gasdermin D pathway,and finally induces DIC through phosphatidylserine exposure.Based on this finding,novel gallic acid-modified Mo-based polyoxometalate dots(M-dots)with outstanding antioxidant activity are developed to provide ideal and efficient inhibition of DIC.As expected,M-dots are capable of markedly inhibiting sepsis-caused coagulation,organ injury,and death in sepsis.This therapeutic strategy,blocking the upstream pathway of coagulation rather than coagulation itself,can avoid the side effects of extensive bleeding caused by conventional anticoagulation therapy,and will provide a new avenue for the efficient treatment of sepsis.
文摘Neuropilins(NRP1 and NRP2)are multifunctional receptor proteins that are involved in nerve,blood vessel,and tumor development.NRP1 was first found to be expressed in neurons,but subsequent studies have demonstrated its surface expression in cells from the endothelium and lymph nodes.NRP1 has been demonstrated to be involved in the occurrence and development of a variety of cancers.NRP1 interacts with various cytokines,such as vascular endothelial growth factor family and its receptor and transforming growth factor p i and its receptor,to affect tumor angiogenesis,tumor proliferation,and migration.In addition,NRP1+regulatory T cells(Tregs)play an inhibitory role in tumor immunity.High numbers of NRP1+Tregs were associated with cancer prognosis.Targeting NRP1 has shown promise,and antagonists against NRP1 have had therapeutic efficacy in preliminary clinical studies.NRP1 treatment modalities using nanomaterials,targeted drugs,oncolytic viruses,and radio-chemotherapy have gradually been developed.Hence,we reviewed the use of NRP1 in the context of tumorigenesis,progression,and treatment.
基金supported by the National Natural Science Foundation of China(No.81972689 and 81772497).
文摘The signal adaptor myeloid differentiation primary response 88(MyD88)of Toll-like receptor(TLR)signaling is universally expressed in immune cells and non-immune cells,and myeloid cells play a significant role in modulating colitis.Macrophages are myeloid lineage cells which is important for maintaining intestinal homeostasis in inflammation.1 And macrophages can recognize invading pathogens through pattern recognition receptors(PRRs),such as TLRs and the nucleotide oligomerization domain(NOD)-like receptor family,pyrin domain-containing 3(NLRP3),and quickly infiltrate the injured site leading to inflammation.2 MyD88 expression in myeloid cells can rescue the intestinal injury induced by dextran sulfate sodium(DSS)in murine models.However,the mechanism whereby MyD88 works in myeloid cells and influence the progress of the disease remain elusive.In this study,we used DSS induced colitis mouse model and found Lysm-cre-MyD88fl/fl(MyD88ΔМΦ)mice were more susceptible to colitis.The deficiency of MyD88 leads to up-regulation of S100A8,which activate NLRP3 inflammasome and their associated pyroptosis in intestinal epithelial cells in a RAGE dependent manner.Thus,MyD88 signaling in macrophages,which is necessary to maintain intestinal homeostasis,crucially prevents the development of colitis.Our results may shed new lights on potential targets that can be applied in colitis therapy.
基金This work was supported by the National Outstanding Youth Science Fund Project of the National Natural Science Foundation of China(grant no.82022033)Shanghai Rising-Star Program(grant no.19QA1406800)+2 种基金Shanghai Talent Development Fund(grant no.2019040)the Fundamental Research Funds for the Central Universities(22120210561)the program for Shanghai Young Top-Notch Talent.
文摘Oncolytic viruses(OVs)as one promising antitumor methods have made important contributions to tumor immunotherapy,which arouse increasing attention.They provide the dual mechanisms including direct killing effect toward tumor cells and immune activation for elevating antitumor responses,which have been proved in many preclinical studies.Especially,natural or genetically modified viruses as clinical immune preparations have emerged as a new promising approach objective to oncology treatment.The approval of talimogene laherparepvec(T-VEC)by the U.S.Food and Drug Administration(FDA)for the therapy of advanced melanoma could be considered as a milestone achievement in the clinical translation of OV.In this review,we first discussed the antitumor mechanisms of OVs with an emphasis on targeting,replication,and propagation.We further outlined the state of the art of current OVs in tumor and underlined the activated biological effects especially including immunity.More significantly,the enhanced immune responses based on OVs were systematically discussed from different perspectives such as combination with immunotherapy,genetic engineering of OVs,integration with nanobiotechnology or nanoparticles,and antiviral response counteraction,where their principles were shed light on.The development of OVs in the clinics was also highlighted to analyze the actuality and concerns of different OV applications in clinical trials.At last,the future perspectives and challenges of OVs as an already widely accepted treatment means were discussed.This review will provide a systematic review and deep insight into OV development and also offer new opportunities and guidance pathways to drive the further clinical translation.
文摘Current approaches for the treatment of chronic lymphocytic leukemia （CLL） have greatly improved the prognosis for survival, but some patients remain refractive to these therapeutic regimens. Hence, in addition to reducing the long-term side- effects of therapeutics for all leukemia patients, there is an urgent need for novel therapeutic strategies for difficult-to-treat leukemia cases. Due to the cytotoxicity of drugs, the major challenge currently is to deliver the therapeutic agents to neoplastic cells while preserving the viability of non-malignant ceils. In this study, we propose a therapeutic approach in which high doses of hydroxychloroquine and chlorambucil were loaded into biodegradable polymeric nanopartides coated with an anti-CD20 antibody.We first demonstrated the ability of the nanoparticles to target and internalize in tumor B-cells. Moreover, these nanoparticles could kill not only p53-mutated]deleted leukemia cells expressing a low amount of CD20, but also circulating primary ceils isolated from chronic lymphocytic leukemia patients. The safety of these nanoparticles was also demonstrated in healthy mice, and their therapeutic effects were shown in a new model of aggressive leukemia. These results showed that anti-CD20 nanoparticles containing hydroxychloroquine and chlorambucil can be effective in controlling aggressive leukemia and provided a rationale for adopting this approach for the treatment of other B-cell disorders.
