Diabetic retinopathy is a prominent cause of blindness in adults,with early retinal ganglion cell loss contributing to visual dysfunction or blindness.In the brain,defects inγ-aminobutyric acid synaptic transmission ...Diabetic retinopathy is a prominent cause of blindness in adults,with early retinal ganglion cell loss contributing to visual dysfunction or blindness.In the brain,defects inγ-aminobutyric acid synaptic transmission are associated with pathophysiological and neurodegenerative disorders,whereas glucagon-like peptide-1 has demonstrated neuroprotective effects.However,it is not yet clear whether diabetes causes alterations in inhibitory input to retinal ganglion cells and whether and how glucagon-like peptide-1 protects against neurodegeneration in the diabetic retina through regulating inhibitory synaptic transmission to retinal ganglion cells.In the present study,we used the patch-clamp technique to recordγ-aminobutyric acid subtype A receptor-mediated miniature inhibitory postsynaptic currents in retinal ganglion cells from streptozotocin-induced diabetes model rats.We found that early diabetes(4 weeks of hyperglycemia)decreased the frequency of GABAergic miniature inhibitory postsynaptic currents in retinal ganglion cells without altering their amplitude,suggesting a reduction in the spontaneous release ofγ-aminobutyric acid to retinal ganglion cells.Topical administration of glucagon-like peptide-1 eyedrops over a period of 2 weeks effectively countered the hyperglycemia-induced downregulation of GABAergic mIPSC frequency,subsequently enhancing the survival of retinal ganglion cells.Concurrently,the protective effects of glucagon-like peptide-1 on retinal ganglion cells in diabetic rats were eliminated by topical administration of exendin-9-39,a specific glucagon-like peptide-1 receptor antagonist,or SR95531,a specific antagonist of theγ-aminobutyric acid subtype A receptor.Furthermore,extracellular perfusion of glucagon-like peptide-1 was found to elevate the frequencies of GABAergic miniature inhibitory postsynaptic currents in both ON-and OFF-type retinal ganglion cells.This elevation was shown to be mediated by activation of the phosphatidylinositol-phospholipase C/inositol 1,4,5-trisphosphate receptor/Ca2+/protein kinase C signaling pathway downstream of glucagon-like peptide-1 receptor activation.Moreover,multielectrode array recordings revealed that glucagon-like peptide-1 functionally augmented the photoresponses of ON-type retinal ganglion cells.Optomotor response tests demonstrated that diabetic rats exhibited reductions in visual acuity and contrast sensitivity that were significantly ameliorated by topical administration of glucagon-like peptide-1.These results suggest that glucagon-like peptide-1 facilitates the release ofγ-aminobutyric acid onto retinal ganglion cells through the activation of glucagon-like peptide-1 receptor,leading to the de-excitation of retinal ganglion cell circuits and the inhibition of excitotoxic processes associated with diabetic retinopathy.Collectively,our findings indicate that theγ-aminobutyric acid system has potential as a therapeutic target for mitigating early-stage diabetic retinopathy.Furthermore,the topical administration of glucagon-like peptide-1 eyedrops represents a non-invasive and effective treatment approach for managing early-stage diabetic retinopathy.展开更多
INTRODUCTIONSialyl Lewis-X antigen ,correlated with carcinoma, is a group of carbohydrate antigen containing oligosaccharide expressed of embryonic tisue and glycoproteins on cell surface of embryonic tissue[1].The SL...INTRODUCTIONSialyl Lewis-X antigen ,correlated with carcinoma, is a group of carbohydrate antigen containing oligosaccharide expressed of embryonic tisue and glycoproteins on cell surface of embryonic tissue[1].The SLeX antigen located on cell surface is synthesized principally by two enzymes ,al ,3fucosyltransfrease and a2, 3sialyctransferase.In adults ,SLeX antigen is expressed principally on the surfaces of granulocytic cells and some tumor cells .展开更多
AIM: To investigate the role of the mitochondrial pathway in JTE-522-induced apoptosis and to investigate the relationship between cytochrome C release, caspase activity and loss of mitochondrial membrane potential (D...AIM: To investigate the role of the mitochondrial pathway in JTE-522-induced apoptosis and to investigate the relationship between cytochrome C release, caspase activity and loss of mitochondrial membrane potential (Deltapsim). METHODS: Cell culture, cell counting, ELISA assay, TUNEL, flow cytometry, Western blot and fluorometric assay were employed to investigate the effect of JTE-522 on cell proliferation and apoptosis in AGS cells and related molecular mechanism. RESULTS: JTE-522 inhibited the growth of AGS cells and induced the apoptosis. Caspases 8 and 9 were activated during apoptosis as judged by the appearance of cleavage products from procaspase and the caspase activities to cleave specific fluorogenic substrates. To elucidate whether the activation of caspases 8 and 9 was required for the apoptosis induction, we examined the effect of caspase-specific inhibitors on apoptosis. The results showed that caspase inhibitors significantly inhibited the apoptosis induced by JTE-522. In addition, the membrane translocation of Bax and cytosolic release of cytochrome C accompanying with the decrease of the uptake of Rhodamin 123, were detected at an early stage of apoptosis. Furthermore, Bax translocation, cytochrome C release, and caspase 9 activation were blocked by Z-VAD.fmk and Z-IETD-CHO. CONCLUSION: The present data indicate a crucial association between activation of caspases 8, 9, cytochrome C release, membrane translocation of Bax, loss of Deltapsim and JTE-522-induced apoptosis in AGS cells.展开更多
Objective:To evaluate the effectiveness of direct-acting antivirals(DAAs)in patients with chronic hepatitis C,assess changes in liver function and hepatic fibrosis following treatment,and identify independent predicto...Objective:To evaluate the effectiveness of direct-acting antivirals(DAAs)in patients with chronic hepatitis C,assess changes in liver function and hepatic fibrosis following treatment,and identify independent predictors of treatment failure.Methods:This retrospective cohort study included patients who received DAA therapy at Hospital Kuala Lumpur between January 2020 and December 2023.Sustained virologic response(SVR)was assessed at least 12 weeks post-treatment by reverse transcription-polymerase chain reaction for hepatitis C virus(HCV)RNA.Demographic,clinical,and laboratory data were collected and analyzed.Multiple logistic regression analysis was performed to identify independent predictors of treatment failure.Results:A total of 335 patients in the study.The overall SVR rate was 89%.After achieving SVR,significant improvements were observed in liver enzyme levels and non-invasive liver fibrosis scores,whereas the overall Model for End-Stage Liver Disease(MELD)scores remained unchanged.Significant independent predictors of treatment failure included non-compliance with DAA therapy[adjusted odds ratio(aOR)68.3;95%confidence interval(95%CI)16.3-285.0;P<0.001],treatment with sofosbuvir/velpatasvir(aOR 6.1;95%CI 1.4-26.5;P=0.015),MELD score of 10-15(aOR 4.6;95%CI 1.1-18.2;P=0.031),HCV genotype 3 infection(aOR 4.5;95%CI 1.1-17.6;P=0.031),and elevated serum total bilirubin level(aOR 1.1;95%CI 1.0-1.1;P=0.003).Conclusions:DAA therapy yielded a high SVR rate,and treatment failure was strongly associated with non-adherence to therapy and advanced liver disease.These findings underscore the necessity of adherence support,early diagnosis,and individualized clinical management to optimize treatment outcomes in patients with chronic hepatitis C.展开更多
We report a theoretical investigation into superconductivity within the MAXH_(6) quaternary hydride system using first-principles calculations,where M and A denote alkali and alkaline earth elements,respectively,and X...We report a theoretical investigation into superconductivity within the MAXH_(6) quaternary hydride system using first-principles calculations,where M and A denote alkali and alkaline earth elements,respectively,and X represents transition metal elements.Systematic analysis of electronic band structures,phonon dispersions,and electron-phonon coupling reveals that substitution of MA binary metal combinations and X metal atoms can create favorable conditions for superconductivity.Mapping of superconducting critical temperatures,combined with dynamical stability analysis through phonon calculations,identifies ten superconducting candidates at ambient pressure.Among these,LiNaAgH_(6) exhibits nearly-free-electron behavior reminiscent of monovalent electron superconductors.It demonstrates exceptional superconducting properties with electron–phonon coupling λ=2.707,which yields a superconducting transition temperature T_(c) of 206.4 K using the Allen–Dynes formula.Its structural analogs MgNaPdH_(6),LiMgPdH_(6),LiMgAgH_(6),LiMgAuH_(6) all exhibit superconducting transition temperatures above 110 K.These findings advance our fundamental understanding of superconductivity in quaternary hydrides and provide guidance for rational design of new high-temperature superconducting materials.展开更多
Osteoclast differentiation depends on receptor activator of nuclear factor-κB(RANK) signaling,which can be divided into triggering,amplifying and targeting phases based on how active the master regulator nuclear fact...Osteoclast differentiation depends on receptor activator of nuclear factor-κB(RANK) signaling,which can be divided into triggering,amplifying and targeting phases based on how active the master regulator nuclear factor of activated T-cells cytoplasmic 1(NFATc1) is. The triggering phase is characterized by immediateearly RANK signaling induced by RANK ligand(RANKL) stimulation mediated by three adaptor proteins,tumor necrosis factor receptor-associated factor 6,Grb-2-associated binder-2 and phospholipase C(PLC)γ2,leading to activation of IκB kinase,mitogen-activated protein kinases and the transcription factors nuclear factor(NF)-κB and activator protein-1(AP-1). Mice lacking NF-κB p50/p52 or the AP-1 subunit c-Fos(encoded by Fos) exhibit severe osteopetrosis due to a differentiation block in the osteoclast lineage. The amplification phase occurs about 24 h later in a RANKLinduced osteoclastogenic culture when Ca2+ oscillation starts and the transcription factor NFATc1 is abundantly produced. In addition to Ca2+ oscillation-dependent nuclear translocation and transcriptional auto-induction of NFATc1,a Ca2+ oscillation-independent,osteoblastdependent mechanism stabilizes NFATc1 protein in dif-ferentiating osteoclasts. Osteoclast precursors lacking PLCγ2,inositol-1,4,5-trisphosphate receptors,regulator of G-protein signaling 10,or NFATc1 show an impaired transition from the triggering to amplifying phases. The final targeting phase is mediated by activation of numerous NFATc1 target genes responsible for cell-cell fusion and regulation of bone-resorptive function. This review focuses on molecular mechanisms for each of the three phases of RANK signaling during osteoclast differentiation.展开更多
INTRODUCTIONBoanmycin (Bleomycin A6, BAM ), a newantitumor antibiotic, was isolated from manycomponents of bleomycin (BLM) produced bystreptomyces pingyangensis which were obtainedfrom a soil sample collected in Pingy...INTRODUCTIONBoanmycin (Bleomycin A6, BAM ), a newantitumor antibiotic, was isolated from manycomponents of bleomycin (BLM) produced bystreptomyces pingyangensis which were obtainedfrom a soil sample collected in Pingyang County,Zhejiang Province, China. Boanmycin has a similarchemical structure to that of BLM, but the terminalamine moiety is different[ 1].展开更多
Various kinds of organisms, including viruses, bacteria, trematodes and fungi are known carcinogens that cause cancer. Infectious identification related to cancer may lead to better treatment for both the prevention a...Various kinds of organisms, including viruses, bacteria, trematodes and fungi are known carcinogens that cause cancer. Infectious identification related to cancer may lead to better treatment for both the prevention and targeting of cancer therapy. Although nearly 20% of all cancers are caused by an infection of a microbe, the amount of evidence and information regarding the mechanisms associated with oncogenesis varies dramatically from one organism to the next. This review cannot be exhaustive because we are not aware of all infections worldwide in addition to their potential mechanisms for oncogenesis. More research is required for all of the species mentioned in this review.展开更多
Objective:To investigate the effect of Catalpa ovata fruit extract(COFE)on muscle growth and exercise performance in C2C12 myoblasts and mice.Me t h o d s:Cel l viabi l i ty was determined through a 3-(4,5-dimethylthi...Objective:To investigate the effect of Catalpa ovata fruit extract(COFE)on muscle growth and exercise performance in C2C12 myoblasts and mice.Me t h o d s:Cel l viabi l i ty was determined through a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay.Myogenic differentiation was observed using Giemsa staining.COFE was administered to mice orally at 50 and 200 mg/kg for 10 weeks.Muscular strength was evaluated using the whole-limb grip strength assay.The expression levels of myogenesis-and energy metabolism-related proteins in vitro and in vivo were determined using Western blotting.Results:COFE significantly improved myoblast-to-myotube differentiation in C2C12 myoblasts.It also increased the expression of myogenesis determination protein 1 and myogenin compared with the control group.Moreover,the expression levels of glucose transporter type 4(Glut4)and peroxisome proliferator-activated receptor-gamma coactivator 1-alpha(PGC-1α)were significantly elevated in the presence of COFE in C2C12 myoblasts.COFE also markedly increased phosphorylation of AMP-activated protein kinase,which regulates Glut4 and PGC-1αexpression levels in C2C12 myoblasts.Mice treated with COFE showed improved grip strength.Myogenesis-and energy metabolism-related protein levels in muscle tissue were significantly increased in COFE-administered mice.Conclusions:COFE treatment improves exercise performance by controlling myogenesis and energy metabolism in skeletal muscle.COFE has the potential to be used as an effective natural agent for enhancing muscular strength.展开更多
The development of Pt-free catalysts for the oxygen reduction reaction(ORR)is a great issue for meeting the cost challenges of proton exchange membrane fuel cells(PEMFCs)in commercial applications.In this work,a serie...The development of Pt-free catalysts for the oxygen reduction reaction(ORR)is a great issue for meeting the cost challenges of proton exchange membrane fuel cells(PEMFCs)in commercial applications.In this work,a series of RuCo/C catalysts were synthesized by NaBH4 reduction method under the premise that the total metal mass percentage was 20%.X-ray diffraction(XRD)patterns and scanning electron microscopy(SEM)confirmed the formation of single-phase nanoparticles with an average size of 33 nm.Cyclic voltammograms(CV)and linear sweep voltammograms(LSV)tests indicated that RuCo(2:1)/C catalyst had the optimal ORR properties.Additionally,the RuCo(2:1)/C catalyst remarkably sustained 98.1% of its activity even after 3000 cycles,surpassing the performance of Pt/C(84.8%).Analysis of the elemental state of the catalyst surface after cycling using X-ray photoelectron spectroscopy(XPS)revealed that the Ru^(0) percentage of RuCo(2:1)/C decreased by 2.2%(from 66.3% to 64.1%),while the Pt^(0) percentage of Pt/C decreased by 7.1%(from 53.3% to 46.2%).It is suggested that the synergy between Ru and Co holds the potential to pave the way for future low-cost and highly stable ORR catalysts,offering significant promise in the context of PEMFCs.展开更多
Background:Os Draconis is an important material in traditional Chinese medicine(TCM).However,its market is saturated with counterfeit products,and the limitations of current identification methods pose a serious threa...Background:Os Draconis is an important material in traditional Chinese medicine(TCM).However,its market is saturated with counterfeit products,and the limitations of current identification methods pose a serious threat to clinical effectiveness and drug safety.This study aims to establish a more accurate and comprehensive authentication system for Os Draconis.Methods:A comprehensive approach was employed to analyze authentic Os Draconis,fossilized Os Draconis,counterfeit products,and lab-prepared modern animal bones.The analytical techniques included ^(14)C dating,electron probe microanalysis(EPMA),polarized light microscopy,X-ray diffraction(XRD),inductively coupled plasma mass spectrometry(ICP-MS),and fourier-transform infrared spectroscopy(FTIR).The study focused on examining the microstructural features and micro-area elemental compositions to identify distinguishing characteristics.Results:Physical identification alone was insufficient to reliably distinguish authentic Os Draconis from its counterfeits.XRD analysis revealed that while hydroxyapatite is the main component in all samples,authentic Os Draconis also contains calcium carbonate and quartz,which were absent in counterfeit and lab-prepared samples.FTIR spectra identified the carbonate ion(CO_(3)^(2-))as a characteristic infrared marker for authentic Os Draconis.ICP-MS analysis showed that Ca and P are the major elements,with a notably high content of Lanthanum(La)among rare earth elements in authentic samples.The EPMA results demonstrated that the Ca/P ratio of authentic Os Draconis is distinct,falling between that of fossilized Os Draconis and counterfeit samples.Conclusion:This study successfully identified several precise markers,including the presence of calcium carbonate,the characteristic CO_(3)^(2-)infrared peak,a high La content,and a specific Ca/P ratio,for the accurate and rapid authentication of Os Draconis.Furthermore,the analysis of its natural porous structure,suitable pore size,and surface area suggests that Os Draconis has significant potential as a natural drug carrier.展开更多
AIM: To study persistence and replication of hepatitis C virus (HCV) in patients' peripheral blood mononuclear cells (PBMC) cultured in vitro. METHODS: Epstein Barr virus (EBV) was used to transform the hepatitis ...AIM: To study persistence and replication of hepatitis C virus (HCV) in patients' peripheral blood mononuclear cells (PBMC) cultured in vitro. METHODS: Epstein Barr virus (EBV) was used to transform the hepatitis C virus from a HCV positive patient to permanent lymphoblastoid cell lines (LCL). Positive and negative HCV RNA strands of the cultured cells and growth media were detected by reverse transcriptase-polymerase chain reaction (RT-PCR) each month. Core and NS5 proteins of HCV were further tested using immunohistochemical SP method and in situ RT-PCR. RESULTS: HCV RNA positive strands were consistently detected the cultured cells for one year. The negative-strand RNA in LCL cells and the positive-strand RNA in supernatants were observed intermittently. Immunohistochemical results medicated expression of HCV NS3 and C proteins in LCL cytoplasm mostly. The positive signal of PCR product was dark blue and mainly localized to the LCL cytoplasm. The RT-PCR signal was eliminated by overnight RNase digestion but not DNase digestion. CONCLUSION: HCV may exist and remain functional in a cultured cell line for a long period.展开更多
The design of this paper is to present the first installment of a complete and final theory of rational human intelligence. The theory is mathematical in the strictest possible sense. The mathematics involved is stric...The design of this paper is to present the first installment of a complete and final theory of rational human intelligence. The theory is mathematical in the strictest possible sense. The mathematics involved is strictly digital—not quantitative in the manner that what is usually thought of as mathematics is quantitative. It is anticipated at this time that the exclusively digital nature of rational human intelligence exhibits four flavors of digitality, apparently no more, and that each flavor will require a lengthy study in its own right. (For more information,please refer to the PDF.)展开更多
The activation of carbon-hydrogen(C-H)bonds is of great scientific importance and offers broad applications in modern organic chemistry[1].In recent years,strategies for C-H bond activation have made notable advances,...The activation of carbon-hydrogen(C-H)bonds is of great scientific importance and offers broad applications in modern organic chemistry[1].In recent years,strategies for C-H bond activation have made notable advances,particularly in the efficient construction of complex molecular architectures.However,most existing C-H activation systems rely on expensive noble metal catalysts,including palladium,rhodium,ruthenium,and iridium.These metals not only come at a high cost but are also often associated with significant toxicity,which further limits their viability and sustainability in industrial applications.展开更多
Hepatitis C virus(HCV)infection,traditionally regarded as a hepatotropic disease,is increasingly recognized as a systemic condition with significant thrombotic implications.Chronic HCV induces a persistent proinflamma...Hepatitis C virus(HCV)infection,traditionally regarded as a hepatotropic disease,is increasingly recognized as a systemic condition with significant thrombotic implications.Chronic HCV induces a persistent proinflammatory and prothrombotic state that substantially elevates the risk of both venous and arterial events.Mechanistically,HCV drives endothelial dysfunction,enhances platelet activation,disrupts coagulation and fibrinolytic balance,and promotes immunemediated vascular injury through cryoglobulinemia and chronic systemic inflammation.Clinical manifestations range from portal vein thrombosis and venous thromboembolism to coronary artery disease and ischemic stroke,highlighting the far-reaching consequences of virus-driven coagulopathy.Emerging evidence challenges the historical view of cirrhosis as a“naturally anticoagulated”state,instead describing a fragile hemostatic balance prone to both bleeding and thrombosis.Directacting antiviral therapy has transformed outcomes,not only achieving sustained virological response but also reversing systemic inflammation,improving endothelial function,and reducing thrombotic complications.However,patients with advanced fibrosis and comorbidities remain at elevated risk despite viral clearance,underscoring the need for ongoing surveillance.This minireview highlights the interplay between hepatic dysfunction,viral-induced inflammation,and cardiovascular sequelae in chronic HCV,emphasizing the importance of integrating thrombotic risk assessment into clinical care and research frameworks.展开更多
AIM: To prepare a cancer vaccine (H(22)-DC) expressing high levels of costimulatory molecules based on fusions of hepatocarcinoma cells (H(22)) with dendritic cells (DC) of mice and to analyze the biological character...AIM: To prepare a cancer vaccine (H(22)-DC) expressing high levels of costimulatory molecules based on fusions of hepatocarcinoma cells (H(22)) with dendritic cells (DC) of mice and to analyze the biological characteristics and induction of specific CTL activity of H(22)-DC. METHODS: DCs were isolated from murine spleen by metrizamide density gradient centrifugation, purified based on its characteristics of semi-adhesion to culture plates and FcR-,and were cultured in the medium containing GM-CSF and IL-4. A large number of DC were harvested. DCs were then fused with H(22) cells by PEG and the fusion cells were marked with CD11c MicroBeads. The H(22)-DC was sorted with Mimi MACS sorter. The techniques of cell culture, immunocytochemistry and light microscopy were also used to test the characteristics of growth and morphology of H(22)-DC in vitro. As the immunogen, H(22)-DC was inoculated subcutaneously into the right armpit of BALB/C mice, and their tumorigenicity in vivo was observed. MTT was used to test the CTL activity of murine spleen in vivo. RESULTS: DC cells isolated and generated were CD11c+ cells with irregular shape, and highly expressed CD80, CD86 and CD54 molecules. H22 cells were CD11c- cells with spherical shape and bigger volume, and did not express CD80, CD86 and CD54 molecules.H(22)-DC was CD11c+ cells with bigger volume, being spherical, flat or irregular in shape, and highly expressed CD80, CD86 and CD54 molecules, too. H(22)-DC was able to divide and proliferate in vitro, but its activity of proliferation was significantly decreased as compared with H(22) cells and its growth curve was flatter than H(22) cells. After subcutaneous inoculation over 60 days, H(22)-DC showed no tumorigenecity in mice, which was significantly different from control groups (P【0.01). The spleen CTL activity against H(22) cells in mice implanted with fresh H(22)-DC was significantly higher than control groups (P 【 0.01). CONCLUSION: H(22)-DC could significantly stimulate the specific CTL activity of murine spleen, which suggests that the fusion cells have already obtained the function of antigen presenting of parental DC and could present H(22)specific antigen which has not been identified yet, and H(22)-DC could induce antitumor immune response; although simply mixed H(22) cells with DC could stimulate the specific CTL activity which could inhibit the growth of tumor in some degree, it could not prevent the generation of tumor. It shows that the DC vaccine is likely to become a helpful approach in immunotherapy of hepatocarcinoma.展开更多
AIM: To establish clone cells with different metastatic potential for the study of metastasis-related mechanisms. METHODS: Cloning procedure was performed on parental hepatocellular carcinoma (HCC) cell line MHCC97, a...AIM: To establish clone cells with different metastatic potential for the study of metastasis-related mechanisms. METHODS: Cloning procedure was performed on parental hepatocellular carcinoma (HCC) cell line MHCC97, and biological characteristics of the target clones selected by in vivo screening were studied. RESULTS: Two clones with high (MHCC97-H) and low (MHCC97-L) metastatic potential were isolated from the parent cell line. Compared with MHCC97-L, MHCC97-H had smaller cell size (average cell diameter 43 microm vs 50 microm) and faster in vitro and in vivo growth rate (tumor cell doubling time was 34.2h vs 60.0h). The main ranges of chromosomes were 55-58 in MHCC97-H and 57-62 in MHCC97-L. Boyden chamber in vitro invasion assay demonstrated that the number of penetrating cells through the artificial basement membrane was (37.5 +/- 11.0) cells/field for MHCC97-H vs (17.7 +/- 6.3)/field for MHCC97-L. The proportions of cells in G0-G1 phase, S phase, and G2-M phase for MHCC97-H/MHCC97-L were 0.56/0.65, 0.28/0.25 and 0.16/0.10, respectively, as measured by flow cytometry. The serum AFP levels in nude mice 5wk after orthotopic implantation of tumor tissue were (246 +/- 66) microg.L(-1) for MHCC97-H and (91 +/- 66) microg.L(-1) for MHCC97-L. The pulmonary metastatic rate was 100% (10/10) vs 40% (4/10). CONCLUSION: Two clones of the same genetic background but with different biological behaviors were established, which could be valuable models for investigation on HCC metastasis.展开更多
BACKGROUND Hepatocellular carcinoma(HCC),the sixth most common cancer and fourthleading cause of cancer-related mortality globally,imposes a significant burden in Vietnam due to endemic hepatitis B virus(HBV)and hepat...BACKGROUND Hepatocellular carcinoma(HCC),the sixth most common cancer and fourthleading cause of cancer-related mortality globally,imposes a significant burden in Vietnam due to endemic hepatitis B virus(HBV)and hepatitis C virus(HCV)infections.Accurate prognostication is crucial for optimizing treatment and outcomes.Numerous staging systems exist,including the Barcelona Clinic Liver Cancer(BCLC),Hong Kong Liver Cancer(HKLC),cancer of the liver Italian Program(CLIP),Italian Liver Cancer(ITA.LI.CA),Japan Integrated Staging(JIS),Tokyo Score,and model to estimate survival in ambulatory HCC patients(MESIAH).However,their comparative performance in Vietnamese patients remains underexplored.AIM To compare the prognostic accuracy of seven HCC staging systems in predicting survival and identify the optimal model.METHODS This retrospective cohort study included 987 patients with HCC diagnosed at Nhan dan Gia Dinh Hospital,Vietnam,from January 2016 to December 2023.Patients were staged using BCLC,HKLC,CLIP,ITA.LI.CA,JIS,Tokyo score,and MESIAH.Overall survival was analyzed using Kaplan-Meier methods,and prognostic performance was evaluated via the area under the receiver operating characteristic(ROC)curve,Harrell’s concordance index,and calibration plots.RESULTS The HKLC and BCLC systems demonstrated the highest discriminatory ability,with area under the ROC curves of 0.834 and 0.830,respectively,at 12 months and 0.859 for both systems at 36 months.CLIP and ITA.LI.CA exhibited superior calibration,particularly at 36 months.The JIS system consistently showed the poorest discriminatory performance.Subgroup analyses revealed that HKLC maintained strong performance across different viral etiologies(HBV,HCV,non-B-non-C)and treatment modalities(transarterial chemoembolization,surgery,ablation).CONCLUSION The HKLC and BCLC systems showed superior prognostic performance for Vietnamese patients with HCC,supporting HKLC adoption in clinical practice.展开更多
With global carbon emissions continuing to rise,carbon dioxide(CO_(2))capture and resource utilization have become central challenges in achieving the“dual carbon”goals(carbon peak and carbon neutrality).Traditional...With global carbon emissions continuing to rise,carbon dioxide(CO_(2))capture and resource utilization have become central challenges in achieving the“dual carbon”goals(carbon peak and carbon neutrality).Traditional carbon capture and storage(CCS)technology can only temporarily sequester CO_(2),whereas emerging green catalytic technologies(photo/electro/thermal catalysis)enable the conversion of CO_(2) into high-value chemicals(e.g.,fuels,pharmaceutical intermediates),advancing the closure of the artificial carbon cycle[1,2].展开更多
Hepatocellular carcinoma(HCC) is the fifth most common cancer, and hepatitis C virus(HCV) infection plays a major role in HCC development. The molecular mechanisms by which HCV infection leads to HCC are varied. HCV c...Hepatocellular carcinoma(HCC) is the fifth most common cancer, and hepatitis C virus(HCV) infection plays a major role in HCC development. The molecular mechanisms by which HCV infection leads to HCC are varied. HCV core protein is an important risk factor in HCV-associated liver pathogenesis and can modulate several signaling pathways involved in cell cycle regulation, cell growth promotion, cell proliferation, apoptosis, oxidative stress and lipid metabolism. The dysregulation of signaling pathways such as transforming growth factor β(TGF-β), vascular endothelial growth factor(VEGF), Wnt/β-catenin(WNT), cyclooxygenase-2(COX-2) and peroxisome proliferator-activated receptor α(PPARα) by HCV core protein is implicated in the development of HCC. Therefore, it has been suggested that this protein be considered a favorable target for further studies in the development of HCC. In addition, considering the axial role of these signaling pathways in HCC, they are considered druggable targets for cancer therapy. Therefore, using strategies to limit the dysregulation effects of core protein on these signaling pathways seems necessary to prevent HCV-related HCC.展开更多
基金supported by the National Natural Science Foundation of China,Nos.32070989(to YMZ),31872766(to YMZ),81790640(to XLY),and 82070993(to SJW)the grant from Sanming Project of Medicine in Shenzhen,No.SZSM202011015(to XLY)。
文摘Diabetic retinopathy is a prominent cause of blindness in adults,with early retinal ganglion cell loss contributing to visual dysfunction or blindness.In the brain,defects inγ-aminobutyric acid synaptic transmission are associated with pathophysiological and neurodegenerative disorders,whereas glucagon-like peptide-1 has demonstrated neuroprotective effects.However,it is not yet clear whether diabetes causes alterations in inhibitory input to retinal ganglion cells and whether and how glucagon-like peptide-1 protects against neurodegeneration in the diabetic retina through regulating inhibitory synaptic transmission to retinal ganglion cells.In the present study,we used the patch-clamp technique to recordγ-aminobutyric acid subtype A receptor-mediated miniature inhibitory postsynaptic currents in retinal ganglion cells from streptozotocin-induced diabetes model rats.We found that early diabetes(4 weeks of hyperglycemia)decreased the frequency of GABAergic miniature inhibitory postsynaptic currents in retinal ganglion cells without altering their amplitude,suggesting a reduction in the spontaneous release ofγ-aminobutyric acid to retinal ganglion cells.Topical administration of glucagon-like peptide-1 eyedrops over a period of 2 weeks effectively countered the hyperglycemia-induced downregulation of GABAergic mIPSC frequency,subsequently enhancing the survival of retinal ganglion cells.Concurrently,the protective effects of glucagon-like peptide-1 on retinal ganglion cells in diabetic rats were eliminated by topical administration of exendin-9-39,a specific glucagon-like peptide-1 receptor antagonist,or SR95531,a specific antagonist of theγ-aminobutyric acid subtype A receptor.Furthermore,extracellular perfusion of glucagon-like peptide-1 was found to elevate the frequencies of GABAergic miniature inhibitory postsynaptic currents in both ON-and OFF-type retinal ganglion cells.This elevation was shown to be mediated by activation of the phosphatidylinositol-phospholipase C/inositol 1,4,5-trisphosphate receptor/Ca2+/protein kinase C signaling pathway downstream of glucagon-like peptide-1 receptor activation.Moreover,multielectrode array recordings revealed that glucagon-like peptide-1 functionally augmented the photoresponses of ON-type retinal ganglion cells.Optomotor response tests demonstrated that diabetic rats exhibited reductions in visual acuity and contrast sensitivity that were significantly ameliorated by topical administration of glucagon-like peptide-1.These results suggest that glucagon-like peptide-1 facilitates the release ofγ-aminobutyric acid onto retinal ganglion cells through the activation of glucagon-like peptide-1 receptor,leading to the de-excitation of retinal ganglion cell circuits and the inhibition of excitotoxic processes associated with diabetic retinopathy.Collectively,our findings indicate that theγ-aminobutyric acid system has potential as a therapeutic target for mitigating early-stage diabetic retinopathy.Furthermore,the topical administration of glucagon-like peptide-1 eyedrops represents a non-invasive and effective treatment approach for managing early-stage diabetic retinopathy.
文摘INTRODUCTIONSialyl Lewis-X antigen ,correlated with carcinoma, is a group of carbohydrate antigen containing oligosaccharide expressed of embryonic tisue and glycoproteins on cell surface of embryonic tissue[1].The SLeX antigen located on cell surface is synthesized principally by two enzymes ,al ,3fucosyltransfrease and a2, 3sialyctransferase.In adults ,SLeX antigen is expressed principally on the surfaces of granulocytic cells and some tumor cells .
基金National Natural Science Foundation of China,No.39770300,30070873the Overseas Chinese Affairs Office of the State Council Foundation,No.98-33
文摘AIM: To investigate the role of the mitochondrial pathway in JTE-522-induced apoptosis and to investigate the relationship between cytochrome C release, caspase activity and loss of mitochondrial membrane potential (Deltapsim). METHODS: Cell culture, cell counting, ELISA assay, TUNEL, flow cytometry, Western blot and fluorometric assay were employed to investigate the effect of JTE-522 on cell proliferation and apoptosis in AGS cells and related molecular mechanism. RESULTS: JTE-522 inhibited the growth of AGS cells and induced the apoptosis. Caspases 8 and 9 were activated during apoptosis as judged by the appearance of cleavage products from procaspase and the caspase activities to cleave specific fluorogenic substrates. To elucidate whether the activation of caspases 8 and 9 was required for the apoptosis induction, we examined the effect of caspase-specific inhibitors on apoptosis. The results showed that caspase inhibitors significantly inhibited the apoptosis induced by JTE-522. In addition, the membrane translocation of Bax and cytosolic release of cytochrome C accompanying with the decrease of the uptake of Rhodamin 123, were detected at an early stage of apoptosis. Furthermore, Bax translocation, cytochrome C release, and caspase 9 activation were blocked by Z-VAD.fmk and Z-IETD-CHO. CONCLUSION: The present data indicate a crucial association between activation of caspases 8, 9, cytochrome C release, membrane translocation of Bax, loss of Deltapsim and JTE-522-induced apoptosis in AGS cells.
文摘Objective:To evaluate the effectiveness of direct-acting antivirals(DAAs)in patients with chronic hepatitis C,assess changes in liver function and hepatic fibrosis following treatment,and identify independent predictors of treatment failure.Methods:This retrospective cohort study included patients who received DAA therapy at Hospital Kuala Lumpur between January 2020 and December 2023.Sustained virologic response(SVR)was assessed at least 12 weeks post-treatment by reverse transcription-polymerase chain reaction for hepatitis C virus(HCV)RNA.Demographic,clinical,and laboratory data were collected and analyzed.Multiple logistic regression analysis was performed to identify independent predictors of treatment failure.Results:A total of 335 patients in the study.The overall SVR rate was 89%.After achieving SVR,significant improvements were observed in liver enzyme levels and non-invasive liver fibrosis scores,whereas the overall Model for End-Stage Liver Disease(MELD)scores remained unchanged.Significant independent predictors of treatment failure included non-compliance with DAA therapy[adjusted odds ratio(aOR)68.3;95%confidence interval(95%CI)16.3-285.0;P<0.001],treatment with sofosbuvir/velpatasvir(aOR 6.1;95%CI 1.4-26.5;P=0.015),MELD score of 10-15(aOR 4.6;95%CI 1.1-18.2;P=0.031),HCV genotype 3 infection(aOR 4.5;95%CI 1.1-17.6;P=0.031),and elevated serum total bilirubin level(aOR 1.1;95%CI 1.0-1.1;P=0.003).Conclusions:DAA therapy yielded a high SVR rate,and treatment failure was strongly associated with non-adherence to therapy and advanced liver disease.These findings underscore the necessity of adherence support,early diagnosis,and individualized clinical management to optimize treatment outcomes in patients with chronic hepatitis C.
基金supported by the National Key R&D Program of China (Grant No.2022YFA1403201)the National Natural Science Foundation of China (Grant Nos.12125404,T2495231,123B2049,and 12204138)+9 种基金the Advanced MaterialsNational Science and Technology Major Project (Grant No.2024ZD0607000)the Natural Science Foundation of Jiangsu Province (Grant Nos.BK20233001 and BK20253009)the Jiangsu Funding Program for Excellent Postdoctoral Talent (Grant No.2024ZB002)the China Postdoctoral Science Foundation (Grant No.2025M773331)the Fundamental and Interdisciplinary Disciplines Breakthrough Plan of the Ministry of Education of Chinathe AI&AI for Science program of Nanjing UniversityArtificial Intelligence and Quantum physics (AIQ) program of Nanjing Universitythe Fundamental Research Funds for the Central Universitiesthe Natural Science Foundation of Nanjing University of Posts and Telecommunications(Grant Nos.NY224165,NY220038,and NY219087)the Hua Li Talents Program of Nanjing University of Posts and Telecommunications。
文摘We report a theoretical investigation into superconductivity within the MAXH_(6) quaternary hydride system using first-principles calculations,where M and A denote alkali and alkaline earth elements,respectively,and X represents transition metal elements.Systematic analysis of electronic band structures,phonon dispersions,and electron-phonon coupling reveals that substitution of MA binary metal combinations and X metal atoms can create favorable conditions for superconductivity.Mapping of superconducting critical temperatures,combined with dynamical stability analysis through phonon calculations,identifies ten superconducting candidates at ambient pressure.Among these,LiNaAgH_(6) exhibits nearly-free-electron behavior reminiscent of monovalent electron superconductors.It demonstrates exceptional superconducting properties with electron–phonon coupling λ=2.707,which yields a superconducting transition temperature T_(c) of 206.4 K using the Allen–Dynes formula.Its structural analogs MgNaPdH_(6),LiMgPdH_(6),LiMgAgH_(6),LiMgAuH_(6) all exhibit superconducting transition temperatures above 110 K.These findings advance our fundamental understanding of superconductivity in quaternary hydrides and provide guidance for rational design of new high-temperature superconducting materials.
基金Supported by Grants from MEXT Japan,No.23790265(to Kuroda Y)and No.21390425(to Matsuo K)
文摘Osteoclast differentiation depends on receptor activator of nuclear factor-κB(RANK) signaling,which can be divided into triggering,amplifying and targeting phases based on how active the master regulator nuclear factor of activated T-cells cytoplasmic 1(NFATc1) is. The triggering phase is characterized by immediateearly RANK signaling induced by RANK ligand(RANKL) stimulation mediated by three adaptor proteins,tumor necrosis factor receptor-associated factor 6,Grb-2-associated binder-2 and phospholipase C(PLC)γ2,leading to activation of IκB kinase,mitogen-activated protein kinases and the transcription factors nuclear factor(NF)-κB and activator protein-1(AP-1). Mice lacking NF-κB p50/p52 or the AP-1 subunit c-Fos(encoded by Fos) exhibit severe osteopetrosis due to a differentiation block in the osteoclast lineage. The amplification phase occurs about 24 h later in a RANKLinduced osteoclastogenic culture when Ca2+ oscillation starts and the transcription factor NFATc1 is abundantly produced. In addition to Ca2+ oscillation-dependent nuclear translocation and transcriptional auto-induction of NFATc1,a Ca2+ oscillation-independent,osteoblastdependent mechanism stabilizes NFATc1 protein in dif-ferentiating osteoclasts. Osteoclast precursors lacking PLCγ2,inositol-1,4,5-trisphosphate receptors,regulator of G-protein signaling 10,or NFATc1 show an impaired transition from the triggering to amplifying phases. The final targeting phase is mediated by activation of numerous NFATc1 target genes responsible for cell-cell fusion and regulation of bone-resorptive function. This review focuses on molecular mechanisms for each of the three phases of RANK signaling during osteoclast differentiation.
基金Supported by the National Natural Science Foundation of China, No. 93090012-03
文摘INTRODUCTIONBoanmycin (Bleomycin A6, BAM ), a newantitumor antibiotic, was isolated from manycomponents of bleomycin (BLM) produced bystreptomyces pingyangensis which were obtainedfrom a soil sample collected in Pingyang County,Zhejiang Province, China. Boanmycin has a similarchemical structure to that of BLM, but the terminalamine moiety is different[ 1].
文摘Various kinds of organisms, including viruses, bacteria, trematodes and fungi are known carcinogens that cause cancer. Infectious identification related to cancer may lead to better treatment for both the prevention and targeting of cancer therapy. Although nearly 20% of all cancers are caused by an infection of a microbe, the amount of evidence and information regarding the mechanisms associated with oncogenesis varies dramatically from one organism to the next. This review cannot be exhaustive because we are not aware of all infections worldwide in addition to their potential mechanisms for oncogenesis. More research is required for all of the species mentioned in this review.
基金supported by Project to Make Multi-Ministerial National Biological Research Resources More Advanced Program,Korea Environment Industry&Technology Institute,and funded by Korea Ministry of Environment(grant number RS-2023-00230403).
文摘Objective:To investigate the effect of Catalpa ovata fruit extract(COFE)on muscle growth and exercise performance in C2C12 myoblasts and mice.Me t h o d s:Cel l viabi l i ty was determined through a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay.Myogenic differentiation was observed using Giemsa staining.COFE was administered to mice orally at 50 and 200 mg/kg for 10 weeks.Muscular strength was evaluated using the whole-limb grip strength assay.The expression levels of myogenesis-and energy metabolism-related proteins in vitro and in vivo were determined using Western blotting.Results:COFE significantly improved myoblast-to-myotube differentiation in C2C12 myoblasts.It also increased the expression of myogenesis determination protein 1 and myogenin compared with the control group.Moreover,the expression levels of glucose transporter type 4(Glut4)and peroxisome proliferator-activated receptor-gamma coactivator 1-alpha(PGC-1α)were significantly elevated in the presence of COFE in C2C12 myoblasts.COFE also markedly increased phosphorylation of AMP-activated protein kinase,which regulates Glut4 and PGC-1αexpression levels in C2C12 myoblasts.Mice treated with COFE showed improved grip strength.Myogenesis-and energy metabolism-related protein levels in muscle tissue were significantly increased in COFE-administered mice.Conclusions:COFE treatment improves exercise performance by controlling myogenesis and energy metabolism in skeletal muscle.COFE has the potential to be used as an effective natural agent for enhancing muscular strength.
基金Funded by the 111 Project(No.B17034)Open Project of Hubei Key Laboratory of Power System Design and Test for Electrical Vehicle(No.ZDSYS202212)+1 种基金Innovative Research Team Development Program of Ministry of Education of China(No.IRT_17R83)the Science and Technology Project of China Southern Power Grid Co.,Ltd.(No.GDKJXM20222546)。
文摘The development of Pt-free catalysts for the oxygen reduction reaction(ORR)is a great issue for meeting the cost challenges of proton exchange membrane fuel cells(PEMFCs)in commercial applications.In this work,a series of RuCo/C catalysts were synthesized by NaBH4 reduction method under the premise that the total metal mass percentage was 20%.X-ray diffraction(XRD)patterns and scanning electron microscopy(SEM)confirmed the formation of single-phase nanoparticles with an average size of 33 nm.Cyclic voltammograms(CV)and linear sweep voltammograms(LSV)tests indicated that RuCo(2:1)/C catalyst had the optimal ORR properties.Additionally,the RuCo(2:1)/C catalyst remarkably sustained 98.1% of its activity even after 3000 cycles,surpassing the performance of Pt/C(84.8%).Analysis of the elemental state of the catalyst surface after cycling using X-ray photoelectron spectroscopy(XPS)revealed that the Ru^(0) percentage of RuCo(2:1)/C decreased by 2.2%(from 66.3% to 64.1%),while the Pt^(0) percentage of Pt/C decreased by 7.1%(from 53.3% to 46.2%).It is suggested that the synergy between Ru and Co holds the potential to pave the way for future low-cost and highly stable ORR catalysts,offering significant promise in the context of PEMFCs.
基金supported by the Scientific and Technological Innovation Project of the China Academy of Chinese Medical Sciences(CI2021A04013)the National Natural Science Foundation of China(82204610)+1 种基金the Qihang Talent Program(L2022046)the Fundamental Research Funds for the Central Public Welfare Research Institutes(ZZ15-YQ-041 and L2021029).
文摘Background:Os Draconis is an important material in traditional Chinese medicine(TCM).However,its market is saturated with counterfeit products,and the limitations of current identification methods pose a serious threat to clinical effectiveness and drug safety.This study aims to establish a more accurate and comprehensive authentication system for Os Draconis.Methods:A comprehensive approach was employed to analyze authentic Os Draconis,fossilized Os Draconis,counterfeit products,and lab-prepared modern animal bones.The analytical techniques included ^(14)C dating,electron probe microanalysis(EPMA),polarized light microscopy,X-ray diffraction(XRD),inductively coupled plasma mass spectrometry(ICP-MS),and fourier-transform infrared spectroscopy(FTIR).The study focused on examining the microstructural features and micro-area elemental compositions to identify distinguishing characteristics.Results:Physical identification alone was insufficient to reliably distinguish authentic Os Draconis from its counterfeits.XRD analysis revealed that while hydroxyapatite is the main component in all samples,authentic Os Draconis also contains calcium carbonate and quartz,which were absent in counterfeit and lab-prepared samples.FTIR spectra identified the carbonate ion(CO_(3)^(2-))as a characteristic infrared marker for authentic Os Draconis.ICP-MS analysis showed that Ca and P are the major elements,with a notably high content of Lanthanum(La)among rare earth elements in authentic samples.The EPMA results demonstrated that the Ca/P ratio of authentic Os Draconis is distinct,falling between that of fossilized Os Draconis and counterfeit samples.Conclusion:This study successfully identified several precise markers,including the presence of calcium carbonate,the characteristic CO_(3)^(2-)infrared peak,a high La content,and a specific Ca/P ratio,for the accurate and rapid authentication of Os Draconis.Furthermore,the analysis of its natural porous structure,suitable pore size,and surface area suggests that Os Draconis has significant potential as a natural drug carrier.
基金The paper was support by a grant from the Ministry Youth Research of China,No.98-1-269
文摘AIM: To study persistence and replication of hepatitis C virus (HCV) in patients' peripheral blood mononuclear cells (PBMC) cultured in vitro. METHODS: Epstein Barr virus (EBV) was used to transform the hepatitis C virus from a HCV positive patient to permanent lymphoblastoid cell lines (LCL). Positive and negative HCV RNA strands of the cultured cells and growth media were detected by reverse transcriptase-polymerase chain reaction (RT-PCR) each month. Core and NS5 proteins of HCV were further tested using immunohistochemical SP method and in situ RT-PCR. RESULTS: HCV RNA positive strands were consistently detected the cultured cells for one year. The negative-strand RNA in LCL cells and the positive-strand RNA in supernatants were observed intermittently. Immunohistochemical results medicated expression of HCV NS3 and C proteins in LCL cytoplasm mostly. The positive signal of PCR product was dark blue and mainly localized to the LCL cytoplasm. The RT-PCR signal was eliminated by overnight RNase digestion but not DNase digestion. CONCLUSION: HCV may exist and remain functional in a cultured cell line for a long period.
文摘The design of this paper is to present the first installment of a complete and final theory of rational human intelligence. The theory is mathematical in the strictest possible sense. The mathematics involved is strictly digital—not quantitative in the manner that what is usually thought of as mathematics is quantitative. It is anticipated at this time that the exclusively digital nature of rational human intelligence exhibits four flavors of digitality, apparently no more, and that each flavor will require a lengthy study in its own right. (For more information,please refer to the PDF.)
文摘The activation of carbon-hydrogen(C-H)bonds is of great scientific importance and offers broad applications in modern organic chemistry[1].In recent years,strategies for C-H bond activation have made notable advances,particularly in the efficient construction of complex molecular architectures.However,most existing C-H activation systems rely on expensive noble metal catalysts,including palladium,rhodium,ruthenium,and iridium.These metals not only come at a high cost but are also often associated with significant toxicity,which further limits their viability and sustainability in industrial applications.
文摘Hepatitis C virus(HCV)infection,traditionally regarded as a hepatotropic disease,is increasingly recognized as a systemic condition with significant thrombotic implications.Chronic HCV induces a persistent proinflammatory and prothrombotic state that substantially elevates the risk of both venous and arterial events.Mechanistically,HCV drives endothelial dysfunction,enhances platelet activation,disrupts coagulation and fibrinolytic balance,and promotes immunemediated vascular injury through cryoglobulinemia and chronic systemic inflammation.Clinical manifestations range from portal vein thrombosis and venous thromboembolism to coronary artery disease and ischemic stroke,highlighting the far-reaching consequences of virus-driven coagulopathy.Emerging evidence challenges the historical view of cirrhosis as a“naturally anticoagulated”state,instead describing a fragile hemostatic balance prone to both bleeding and thrombosis.Directacting antiviral therapy has transformed outcomes,not only achieving sustained virological response but also reversing systemic inflammation,improving endothelial function,and reducing thrombotic complications.However,patients with advanced fibrosis and comorbidities remain at elevated risk despite viral clearance,underscoring the need for ongoing surveillance.This minireview highlights the interplay between hepatic dysfunction,viral-induced inflammation,and cardiovascular sequelae in chronic HCV,emphasizing the importance of integrating thrombotic risk assessment into clinical care and research frameworks.
基金Supported jby the Natural Science Foundation of Guangdong Province China,No.980180
文摘AIM: To prepare a cancer vaccine (H(22)-DC) expressing high levels of costimulatory molecules based on fusions of hepatocarcinoma cells (H(22)) with dendritic cells (DC) of mice and to analyze the biological characteristics and induction of specific CTL activity of H(22)-DC. METHODS: DCs were isolated from murine spleen by metrizamide density gradient centrifugation, purified based on its characteristics of semi-adhesion to culture plates and FcR-,and were cultured in the medium containing GM-CSF and IL-4. A large number of DC were harvested. DCs were then fused with H(22) cells by PEG and the fusion cells were marked with CD11c MicroBeads. The H(22)-DC was sorted with Mimi MACS sorter. The techniques of cell culture, immunocytochemistry and light microscopy were also used to test the characteristics of growth and morphology of H(22)-DC in vitro. As the immunogen, H(22)-DC was inoculated subcutaneously into the right armpit of BALB/C mice, and their tumorigenicity in vivo was observed. MTT was used to test the CTL activity of murine spleen in vivo. RESULTS: DC cells isolated and generated were CD11c+ cells with irregular shape, and highly expressed CD80, CD86 and CD54 molecules. H22 cells were CD11c- cells with spherical shape and bigger volume, and did not express CD80, CD86 and CD54 molecules.H(22)-DC was CD11c+ cells with bigger volume, being spherical, flat or irregular in shape, and highly expressed CD80, CD86 and CD54 molecules, too. H(22)-DC was able to divide and proliferate in vitro, but its activity of proliferation was significantly decreased as compared with H(22) cells and its growth curve was flatter than H(22) cells. After subcutaneous inoculation over 60 days, H(22)-DC showed no tumorigenecity in mice, which was significantly different from control groups (P【0.01). The spleen CTL activity against H(22) cells in mice implanted with fresh H(22)-DC was significantly higher than control groups (P 【 0.01). CONCLUSION: H(22)-DC could significantly stimulate the specific CTL activity of murine spleen, which suggests that the fusion cells have already obtained the function of antigen presenting of parental DC and could present H(22)specific antigen which has not been identified yet, and H(22)-DC could induce antitumor immune response; although simply mixed H(22) cells with DC could stimulate the specific CTL activity which could inhibit the growth of tumor in some degree, it could not prevent the generation of tumor. It shows that the DC vaccine is likely to become a helpful approach in immunotherapy of hepatocarcinoma.
基金Supportod ty the State Key Basic Research Program Grant G1998051211 the Fund for Leading Specialty of Shanghai Metropolitan Bureau of Public Health.
文摘AIM: To establish clone cells with different metastatic potential for the study of metastasis-related mechanisms. METHODS: Cloning procedure was performed on parental hepatocellular carcinoma (HCC) cell line MHCC97, and biological characteristics of the target clones selected by in vivo screening were studied. RESULTS: Two clones with high (MHCC97-H) and low (MHCC97-L) metastatic potential were isolated from the parent cell line. Compared with MHCC97-L, MHCC97-H had smaller cell size (average cell diameter 43 microm vs 50 microm) and faster in vitro and in vivo growth rate (tumor cell doubling time was 34.2h vs 60.0h). The main ranges of chromosomes were 55-58 in MHCC97-H and 57-62 in MHCC97-L. Boyden chamber in vitro invasion assay demonstrated that the number of penetrating cells through the artificial basement membrane was (37.5 +/- 11.0) cells/field for MHCC97-H vs (17.7 +/- 6.3)/field for MHCC97-L. The proportions of cells in G0-G1 phase, S phase, and G2-M phase for MHCC97-H/MHCC97-L were 0.56/0.65, 0.28/0.25 and 0.16/0.10, respectively, as measured by flow cytometry. The serum AFP levels in nude mice 5wk after orthotopic implantation of tumor tissue were (246 +/- 66) microg.L(-1) for MHCC97-H and (91 +/- 66) microg.L(-1) for MHCC97-L. The pulmonary metastatic rate was 100% (10/10) vs 40% (4/10). CONCLUSION: Two clones of the same genetic background but with different biological behaviors were established, which could be valuable models for investigation on HCC metastasis.
文摘BACKGROUND Hepatocellular carcinoma(HCC),the sixth most common cancer and fourthleading cause of cancer-related mortality globally,imposes a significant burden in Vietnam due to endemic hepatitis B virus(HBV)and hepatitis C virus(HCV)infections.Accurate prognostication is crucial for optimizing treatment and outcomes.Numerous staging systems exist,including the Barcelona Clinic Liver Cancer(BCLC),Hong Kong Liver Cancer(HKLC),cancer of the liver Italian Program(CLIP),Italian Liver Cancer(ITA.LI.CA),Japan Integrated Staging(JIS),Tokyo Score,and model to estimate survival in ambulatory HCC patients(MESIAH).However,their comparative performance in Vietnamese patients remains underexplored.AIM To compare the prognostic accuracy of seven HCC staging systems in predicting survival and identify the optimal model.METHODS This retrospective cohort study included 987 patients with HCC diagnosed at Nhan dan Gia Dinh Hospital,Vietnam,from January 2016 to December 2023.Patients were staged using BCLC,HKLC,CLIP,ITA.LI.CA,JIS,Tokyo score,and MESIAH.Overall survival was analyzed using Kaplan-Meier methods,and prognostic performance was evaluated via the area under the receiver operating characteristic(ROC)curve,Harrell’s concordance index,and calibration plots.RESULTS The HKLC and BCLC systems demonstrated the highest discriminatory ability,with area under the ROC curves of 0.834 and 0.830,respectively,at 12 months and 0.859 for both systems at 36 months.CLIP and ITA.LI.CA exhibited superior calibration,particularly at 36 months.The JIS system consistently showed the poorest discriminatory performance.Subgroup analyses revealed that HKLC maintained strong performance across different viral etiologies(HBV,HCV,non-B-non-C)and treatment modalities(transarterial chemoembolization,surgery,ablation).CONCLUSION The HKLC and BCLC systems showed superior prognostic performance for Vietnamese patients with HCC,supporting HKLC adoption in clinical practice.
基金supported by the National Natural Science Foundation of China(22472069,22102064,and 22302080)China Postdoctoral Science Foundation(2024M760028).
文摘With global carbon emissions continuing to rise,carbon dioxide(CO_(2))capture and resource utilization have become central challenges in achieving the“dual carbon”goals(carbon peak and carbon neutrality).Traditional carbon capture and storage(CCS)technology can only temporarily sequester CO_(2),whereas emerging green catalytic technologies(photo/electro/thermal catalysis)enable the conversion of CO_(2) into high-value chemicals(e.g.,fuels,pharmaceutical intermediates),advancing the closure of the artificial carbon cycle[1,2].
文摘Hepatocellular carcinoma(HCC) is the fifth most common cancer, and hepatitis C virus(HCV) infection plays a major role in HCC development. The molecular mechanisms by which HCV infection leads to HCC are varied. HCV core protein is an important risk factor in HCV-associated liver pathogenesis and can modulate several signaling pathways involved in cell cycle regulation, cell growth promotion, cell proliferation, apoptosis, oxidative stress and lipid metabolism. The dysregulation of signaling pathways such as transforming growth factor β(TGF-β), vascular endothelial growth factor(VEGF), Wnt/β-catenin(WNT), cyclooxygenase-2(COX-2) and peroxisome proliferator-activated receptor α(PPARα) by HCV core protein is implicated in the development of HCC. Therefore, it has been suggested that this protein be considered a favorable target for further studies in the development of HCC. In addition, considering the axial role of these signaling pathways in HCC, they are considered druggable targets for cancer therapy. Therefore, using strategies to limit the dysregulation effects of core protein on these signaling pathways seems necessary to prevent HCV-related HCC.
