Alcoholic liver disease(ALD), a major cause of chronic liver disease worldwide, poses a serious threat to human health. Despite the availability of various drugs for treating ALD, their efficacy is often uncertain, necessitating the search for new therapeutic approaches. Traditional Chinese medicine polysaccharides have garnered increasing attention in recent years due to their versatility, high efficiency, and low side effects, and they have demonstrated significant potential in preventing and treating ALD. Emerging studies have suggested that these polysaccharides exert their therapeutic effects through multiple mechanisms, including the inhibition of oxidative stress and the regulation of lipid metabolism, gut microbiota, and programmed cell death. This review summarizes the recent research progress in the pharmacological effects and regulatory mechanisms of traditional Chinese medicine polysaccharides in treating ALD, aiming to provide a scientific basis and theoretical support for their application in the prevention and treatment of ALD.
Humans ; Liver Diseases, Alcoholic/metabolism* ; Polysaccharides/administration & dosage* ; Drugs, Chinese Herbal/administration & dosage* ; Animals ; Oxidative Stress/drug effects* ; Medicine, Chinese Traditional ; Gastrointestinal Microbiome/drug effects* ; Lipid Metabolism/drug effects*

This study primarily aimed to investigate the prevalence of human papillomavirus (HPV) and other common pathogens of sexually transmitted infections (STIs) in spermatozoa of infertile men and their effects on semen parameters. These pathogens included Ureaplasma urealyticum, Ureaplasma parvum, Chlamydia trachomatis, Mycoplasma genitalium , herpes simplex virus 2, Neisseria gonorrhoeae, Enterococcus faecalis, Streptococcus agalactiae, Pseudomonas aeruginosa , and Staphylococcus aureus . A total of 1951 men of infertile couples were recruited between 23 March 2023, and 17 May 2023, at the Department of Reproductive Medicine of The First People's Hospital of Yunnan Province (Kunming, China). Multiplex polymerase chain reaction and capillary electrophoresis were used for HPV genotyping. Polymerase chain reaction and electrophoresis were also used to detect the presence of other STIs. The overall prevalence of HPV infection was 12.4%. The top five prevalent HPV subtypes were types 56, 52, 43, 16, and 53 among those tested positive for HPV. Other common infections with high prevalence rates were Ureaplasma urealyticum (28.3%), Ureaplasma parvum (20.4%), and Enterococcus faecalis (9.5%). The prevalence rates of HPV coinfection with Ureaplasma urealyticum, Ureaplasma parvum, Chlamydia trachomatis, Mycoplasma genitalium , herpes simplex virus 2, Neisseria gonorrhoeae, Enterococcus faecalis, Streptococcus agalactiae , and Staphylococcus aureus were 24.8%, 25.4%, 10.6%, 6.4%, 2.4%, 7.9%, 5.9%, 0.9%, and 1.3%, respectively. The semen volume and total sperm count were greatly decreased by HPV infection alone. Coinfection with HPV and Ureaplasma urealyticum significantly reduced sperm motility and viability. Our study shows that coinfection with STIs is highly prevalent in the semen of infertile men and that coinfection with pathogens can seriously affect semen parameters, emphasizing the necessity of semen screening for STIs.
Humans ; Male ; Infertility, Male/epidemiology* ; Coinfection/microbiology* ; Papillomavirus Infections/virology* ; Adult ; Sexually Transmitted Diseases/complications* ; China/epidemiology* ; Staphylococcus aureus/isolation & purification* ; Chlamydia trachomatis/isolation & purification* ; Prevalence ; Mycoplasma genitalium/isolation & purification* ; Ureaplasma urealyticum/isolation & purification* ; Neisseria gonorrhoeae/isolation & purification* ; Enterococcus faecalis/isolation & purification* ; Streptococcus agalactiae/isolation & purification* ; Herpesvirus 2, Human/genetics* ; Pseudomonas aeruginosa/isolation & purification* ; Semen/virology* ; Sperm Motility ; Spermatozoa/microbiology* ; Human Papillomavirus Viruses

Objective:An in vivo mammalian hepatocyte Unscheduled DNA Synthesis(UDS)test was used to evaluate the genotoxicity of Cross-linked Sodium Hyaluronate Gel and Bone Repair Materials,providing experimental evidence for establishing a UDS testing method for medical devices and materials.Methods:0.9％sodium chloride injection and cottonseed oil were used as the solvent for test materials and negative control,respectively.N-dimethylnitrosamine(NDMA)was used as the positive control for the early sampling times,and 2-acetylaminofluorene(2-AAF)was used as the positive control for the late sampling times.SD rats were administered a single dose for toxic exposure,and liver tissues were collected at 4 h and 16 h,respectively.Hepatocytes were isolated using collagenase perfusion.After labeling with 5-ethynyl-2'-deoxyuridine(EdU),and the net average fluorescence intensity(NAFI)of cell nuclei and nucleoplasm was measured by fluorescence microscope.Data from 50 cells were used to analyze the DNA repair level.Results:Compared with the negative control groups,the positive control groups(NDMA and 2-AAF)showed highly statistically significant differences in NAFI(P＜0.01),indicating successful induction of DNA damage.There was no statistically significant differences between the cross-linked sodium hyaluronate gel groups,bone repair material groups and the negative control group(P＞0.05),suggesting that these materials did not significantly induce DNA damage under the experimental conditions.Conclusion:This study first applied EdU labeling technology to the in vivo hepatic UDS assay,achieving non-radioactive labeling through click chemistry reactions.Under the conditions of this study,cross-linked sodium hyaluronate gel and bone repair materials did not exhibit genotoxicity.In the follow-up,the sample range can be expanded and the observation period can be prolonged to further improve the genotoxicity evaluation system of medical devices.

Chronic kidney disease(CKD)is a chronic disease characterized by renal structural damage and dysfunction.At present,there is still a lack of effective therapeutic drugs and prevention and treatment methods for CKD in clinical practice.More and more studies have shown that necroptosis,as a new type of programmed cell death,plays a vital role in the onset and progression of CKD.Targeting key molecules in the necroptosis pathway,such as RIPK1,RIPK3 and MLKL,the development of small molecule inhibitors has become an emerging strategy for the treatment of CKD,and has shown significant potential to pro-tect the kidneys and alleviate renal fibrosis in a variety of in vitro and in vivo models.Therefore,this article summarizes the re-search progress of the mechanism of necroptosis in recent years,and focuses on the potential role of necroptosis in the pathogene-sis of CKD and the therapeutic potential of targeting this path-way,providing a new perspective and research direction for the prevention and treatment of CKD in the future.

Objective:An in vivo mammalian hepatocyte Unscheduled DNA Synthesis(UDS)test was used to evaluate the genotoxicity of Cross-linked Sodium Hyaluronate Gel and Bone Repair Materials,providing experimental evidence for establishing a UDS testing method for medical devices and materials.Methods:0.9％sodium chloride injection and cottonseed oil were used as the solvent for test materials and negative control,respectively.N-dimethylnitrosamine(NDMA)was used as the positive control for the early sampling times,and 2-acetylaminofluorene(2-AAF)was used as the positive control for the late sampling times.SD rats were administered a single dose for toxic exposure,and liver tissues were collected at 4 h and 16 h,respectively.Hepatocytes were isolated using collagenase perfusion.After labeling with 5-ethynyl-2'-deoxyuridine(EdU),and the net average fluorescence intensity(NAFI)of cell nuclei and nucleoplasm was measured by fluorescence microscope.Data from 50 cells were used to analyze the DNA repair level.Results:Compared with the negative control groups,the positive control groups(NDMA and 2-AAF)showed highly statistically significant differences in NAFI(P＜0.01),indicating successful induction of DNA damage.There was no statistically significant differences between the cross-linked sodium hyaluronate gel groups,bone repair material groups and the negative control group(P＞0.05),suggesting that these materials did not significantly induce DNA damage under the experimental conditions.Conclusion:This study first applied EdU labeling technology to the in vivo hepatic UDS assay,achieving non-radioactive labeling through click chemistry reactions.Under the conditions of this study,cross-linked sodium hyaluronate gel and bone repair materials did not exhibit genotoxicity.In the follow-up,the sample range can be expanded and the observation period can be prolonged to further improve the genotoxicity evaluation system of medical devices.

Chronic kidney disease(CKD)is a chronic disease characterized by renal structural damage and dysfunction.At present,there is still a lack of effective therapeutic drugs and prevention and treatment methods for CKD in clinical practice.More and more studies have shown that necroptosis,as a new type of programmed cell death,plays a vital role in the onset and progression of CKD.Targeting key molecules in the necroptosis pathway,such as RIPK1,RIPK3 and MLKL,the development of small molecule inhibitors has become an emerging strategy for the treatment of CKD,and has shown significant potential to pro-tect the kidneys and alleviate renal fibrosis in a variety of in vitro and in vivo models.Therefore,this article summarizes the re-search progress of the mechanism of necroptosis in recent years,and focuses on the potential role of necroptosis in the pathogene-sis of CKD and the therapeutic potential of targeting this path-way,providing a new perspective and research direction for the prevention and treatment of CKD in the future.

Adaptive immunity is a critical component of the human immune system, playing an essential role in identifying antigens and orchestrating a tailored immune response. This review delves into the significant strides made in the development of epitope prediction tools, their integration into vaccine design, and their pivotal role in enhancing immunotherapy strategies. The review emphasizes the transformative potential of these tools in refining our understanding and application of immune responses. Adaptive immunity distinguishes itself from innate immunity by its ability to recognize specific antigens and remember past infections, leading to quicker and more effective responses upon subsequent exposures. This facet of immunity involves complex interactions between various cell types, primarily B cells and T cells, which recognize distinct epitopes presented by antigens. Epitopes are small sequences or configurations on antigens that are recognized by the immune receptors on B cells and T cells, acting as the focal points of immune recognition and response. Epitopes can be broadly classified into two types: linear (or sequential) epitopes and conformational (or discontinuous) epitopes. Linear epitopes consist of a sequence of amino acids in a protein that are recognized by B cells and T cells in their primary structure form. Conformational epitopes, on the other hand, are formed by spatially distinct amino acids that come together in the tertiary structure of the protein, often recognized by the immune system only when the protein folds into its native conformation. The role of epitopes in the immune response is critical as they are the primary triggers for the activation of B cells and T cells. When an epitope is recognized, it can stimulate B cells to produce antibodies, mobilize helper T cells to secrete cytokines, or prompt cytotoxic T cells to kill infected cells. These actions form the basis of the adaptive immune response, tailored to eliminate specific pathogens or infected cells effectively. The prediction of B cell and T cell epitopes has evolved with advances in computational biology, leading to the development of several sophisticated tools that utilize a variety of algorithms to predict the likelihood of epitope regions on antigens. Tools employing machine learning methods, such as support vector machines (SVMs), XGBoost, random forest, analyze large datasets of known epitopes to classify new sequences as potential epitopes based on their similarity to known data. Moreover, deep learning has emerged as a powerful method in epitope prediction, leveraging neural networks capable of learning high-dimensional data from vast amounts of immunological inputs to identify patterns that may not be evident to other predictive models. Deep learning models, such as convolutional neural networks (CNNs), recurrent neural networks (RNNs) and ESM protein language model have demonstrated superior accuracy in mapping the nonlinear relationships inherent in protein structures and epitope interactions. The application of epitope prediction tools in vaccine design is transformative, enabling the development of epitope-based vaccines that can elicit targeted immune responses against specific parts of the pathogen. These vaccines, by focusing the immune response on highly specific regions of the pathogen, can offer high efficacy and reduced side effects. Similarly, in cancer immunotherapy, epitope prediction tools help identify tumor-specific antigens that can be targeted to develop personalized immunotherapeutic strategies, thereby enhancing the precision of cancer treatments. The future of epitope prediction technology appears promising, with ongoing advancements anticipated to enhance the precision and efficiency of these tools further. The integration of broader immunological data, such as patient-specific immune profiles and pathogen variability, along with advances in AI and machine learning, will likely drive the development of more adaptive, robust, and clinically relevant prediction models. This will not only improve the effectiveness of vaccines and immunotherapies but also contribute to our broader understanding of immune mechanisms, potentially leading to breakthroughs in the treatment and prevention of multiple diseases. In conclusion, the development and refinement of epitope prediction tools stand as a cornerstone in the advancement of immunological research and therapeutic design, highlighting a path toward more precise and personalized medicine. The ongoing integration of computational models with experimental immunology holds the promise of revolutionizing our approach to combating infectious diseases and cancer.

Norepinephrine (NE) modulates synaptic transmission and long-term plasticity through distinct subtype adrenergic receptor (AR)-mediated-intracellular signaling cascades. However, the role of NE modulates glutamatergic long-term potentiation (LTP) in the hypothalamic paraventricular nucleus (PVN) magnocellular neuroendocrine cells (MNCs) is unclear. We here investigate the effect of NE on high frequency stimulation (HFS)-induced glutamatergic LTP in rat hypothalamic PVN MNCs in vitro, by whole-cell patch-clamp recording, biocytin staining and pharmacological methods. Delivery of HFS induced glutamatergic LTP with a decrease in N2/N1 ratio in the PVN MNCs, which was enhanced by application of NE (100 nM).HFS-induced LTP was abolished by the blockade of N-methyl-D-aspartate receptors (NMDAR) with D-APV, but it was rescued by the application of NE. NE failed to rescue HFS-induced LTP of MNCs in the presence of a selective β1-AR antagonist, CGP 20712. However, application of β1-AR agonist, dobutamine HCl rescued HFS-induced LTP of MNCs in the absence of NMDAR activity. In the absence of NMDAR activity, NE failed to rescue HFS-induced MNC LTP when protein kinase A (PKA) was inhibited by extracellular applying KT5720 or intracellular administration of PKI. These results indicate that NE activates β1-AR and triggers HFS to induce a novel glutamatergic LTP of hypothalamic PVN NMCs via the postsynaptic PKA signaling pathway in vitro in rats.

Objective To study the effect of panatinib on cholangiocarcinoma(CCA)and its molecular mechanism.Methods QBC939 cells were divided into control group(no treatment),low dose group(0.1 μmol·L-1 panatinib treatment),medium dose group(0.5μmol·L-1panatinib treatment),high dose group(1.0 μmol·L-1 panatinib treatment)and high dose+microRNA-92b-3 group(after treatment with 1.0 μmol·L-1 panatinib transfected miR-92b-3p mimic),high-dose+miR-92b-3p mimic+overexpressed homologous domain interacting protein kinase 3 plasmid(oe-HIPK3)group(after treatment with 1.0 μmol·L-1 panatinib,miR-92b-3p mimic and oe-HIPK3),mimic-NC group(transfected miR-92b-3p NC),and miR-92b-3p mimic group(transfected miR-92b-3p mimic)were transfected.Cell proliferation was detected by cell counting kit 8(CCK-8);cell migration was detected by Transwell,the relative expression level of protein was detected by Western blot.Results Cell proliferation rates of control group,high-dose group,high-dose+miR-92b-3p mimic group,and high-dose+miR-92b-3p mimic group mimic+oe-HIPK3 group were(76.58±8.56)％,(61.85±7.77)％,(74.54±7.68)％and(58.63±6.87)％,respectively;the number of cells migrated were 185.32±20.14,132.33±18.99,168.23±19.85 and 138.66±15.95,respectively;phosphorylated phosphatidyl inositide 3-kinase(p-PI3K)/PI3K ratios were 1.00±0.23,0.68±0.09,0.91±0.18 and 0.60±0.08,respectively;phosphorylated protein kinase B(p-AKT)/AKT ratios were 1.00±0.25,0.61±0.08,1.12±0.28 and 0.72±0.14,respectively.The above indexes were compared with those of the control group in the high-dose group,and those of the high-dose+miR-92b-3p mimic group in the high-dose+miR-92b-3p mimic group in the oe-HIPK3 group.There were statistically significant differences(all P＜0.05).Conclusion Panatinib can effectively inhibit the evil biological behavior of cholangiocarcinoma,which may be related to inhibiting the level of miR-92b-3p and promoting HIPK3-mediated PI3K/AKT signaling pathway.