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Histone deacetylases (HDACs) are zinc-dependent deacetylases that remove acetyl groups from lysine residues of histones or form protein complexes with other proteins for transcriptional repression, changing chromatin structure tightness, and inhibiting gene expression. Recent in vivo and in vitro studies have amply demonstrated the critical role of HDACs in the cell biology of the nervous system during both physiological and pathological processes and have provided new insights into the conduct of research on neurological disease targets. In addition, in vitro and in vivo studies on HDAC inhibitors show promise for the treatment of various diseases. This review summarizes the regulatory mechanisms of HDAC and the important role of its downstream targets in nervous system diseases, and summarizes the therapeutic mechanisms and efficacy of HDAC inhibitors in various nervous system diseases. Additionally, the current pharmacological situation, problems, and developmental prospects of HDAC inhibitors are described. A better understanding of the pathogenic mechanisms of HDACs in the nervous system may reveal new targets for therapeutic interventions in diseases and help to relieve healthcare pressure through preventive measures.

Despite considerable research efforts, inflammatory diseases remain a heavy burden on human health, causing significant economic losses annually. Histone deacetylases (HDACs) play a significant role in regulating inflammation (via histone and non-histone protein deacetylation) and chromatin structure and gene expression regulation. Herein, we present a detailed description of the different HDACs and their functions and analyze the role of HDACs in inflammatory diseases, including pro-inflammatory cytokine production reduction, immune cell function modulation, and anti-inflammatory cell activity enhancement. Although HDAC inhibitors have shown broad inflammatory disease treatment potentials, their clinical applicability remains limited because of their non-specific effects, adverse effects, and drug resistance. With further research and insight, these inhibitors are expected to become important tools for the treatment of a wide range of inflammatory diseases. This review aims to explore the mechanisms and application prospects of HDACs and their inhibitors in multiple inflammatory diseases.

Abstract As an essential marker of cancer treatment, PARP-1 inhibitors could effectively kill tumor cells through a mechanism known as synthetic lethality and are used to treat a variety of cancers. In order to explore novel PARP-1 inhibitors, a series of 22 novel erythrina derivatives were reported and preliminarily explored their mechanism of action. The antitumor activities against four human cancer cell lines including A549, OVCAR-3, HCT-116, and MCF-7 were evaluated, and the preliminary SARs were summarized. Among them, compound 11b exhibited better anti-proliferative effects against A549 cells (IC50 = 1.95 µM). The SI results showed that compound 11b had low toxicity. Moreover, compound 11b displayed excellent PARP-1 inhibitory activities with IC50 values of 19.24 nM. In addition, molecular docking studies provided the rational binding modes of compound 11b in complexes with PARP-1. The flow cytometry assays revealed that compound 11b could induce apoptosis of A549 cells (P

Abstract Accurate and reliable foot measurements at different stances offer comprehensive geometrical information on foot, thus enabling a more comfortable insole/footwear for practical use and daily activities. However, there lacks investigations on continuous deformation of foot shape during the roll-over process. This study analyses the foot deformation of 19 female diabetic patients during half weight bearing standing and self-selected walking speed by using a novel 4D foot scanning system. The scanning system has good repeatability and accuracy in both static and dynamic scanning situations. Point cloud registration for scanned image reorientation and algorithms to automatically extract foot measurements is developed. During the foot roll-over process, maximum deformation of length and girth dimensions are found at first toe contact. Width dimensions have maximum deformation at heel take off. The findings provide a new understanding of foot shape changes in dynamic situations, thus providing an optimal solution for foot comfort, function and protection.

IntroductionResearch on acupuncture for Parkinson's Disease is growing rapidly. A scoping review examines emerging evidence and is important to guide policy and practice. The purpose of this scoping review was to examine the breadth and methodological quality of systematic reviews and meta-analyses, and to map the quality of evidence of these studies to evaluate the efficacy of acupuncture for treatment of PD.MethodsSeven literature databases were searched. Two researchers independently screened the literature and extracted relevant information (such as general characteristics, inclusion criteria, study results, and report quality).The inclusion criteria include publicly published systematic reviews/meta-analyses/systematic reviews of acupuncture treatment for Parkinson's disease. The research subjects are any patients who meet the diagnostic criteria for Parkinson's disease, and intervention measures include acupuncture treatment including electro acupuncture, scalp acupuncture, or combination with other treatment methods. The outcome indicators are all types of results related to PD and the effective measurement tools used.ResultsA total of 23 systematic reviews and/or meta-analyses of studies were included. Most of the articles were published between 2019 and 2023 (47.8%). A total of 14 articles (60.9%) were evaluated and classified, and 89 (36.8.1%) of the 242 included articles were of medium and high quality.DiscussionThis study comprehensively evaluates the quality and research methods of incorporating SRs/MAs, and concludes that acupuncture treatment for Parkinson's disease may be significant. Considering the shortcomings in research design and methodology, it is not possible to draw conclusions on the evidence of acupuncture treatment for PD at this stage, but it does not mean that acupuncture treatment is ineffective. We hope to focus on improving research design and methods in the study of acupuncture treatment for Parkinson's disease, an increase the credibility of research results.

Radiotherapy is the major treatment of non-small cell lung cancer (NSCLC). The radioresistance and toxicity are the main obstacles that leading to therapeutic failure and poor prognosis. Oncogenic mutation, cancer stem cells (CSCs), tumor hypoxia, DNA damage repair, epithelial-mesenchymal transition (EMT), and tumor microenvironment (TME) may dominate the occurrence of radioresistance at different stages of radiotherapy. Chemotherapy drugs, targeted drugs, and immune checkpoint inhibitors are combined with radiotherapy to treat NSCLC to improve the efficacy. This article reviews the potential mechanism of radioresistance in NSCLC, and discusses the current drug research to overcome radioresistance and the advantages of Traditional Chinese medicine (TCM) in improving the efficacy and reducing the toxicity of radiotherapy.

Abstract Background Neuroinflammation is a major driver of age-related brain degeneration and concomitant functional impairment. In patients with Alzheimer’s disease, the most common form of age-related dementia, factors that enhance neuroinflammation may exacerbate disease progression, in part by impairing the glymphatic system responsible for clearance of pathogenic beta-amyloid. Inflammatory bowel diseases (IBDs) induce neuroinflammation and exacerbate cognitive impairment in the elderly. The NACHT-LRR and pyrin (PYD) domain-containing protein 3 (NLRP3) inflammasome has been implicated in neuroinflammation. Therefore, we examined if the NLRP3 inflammasome contributes to glymphatic dysfunction and cognitive impairment in an aging mouse model of IBD. Methods Sixteen-month-old C57BL/6J and NLRP3 knockout (KO) mice received 1% wt/vol dextran sodium sulfate (DSS) in drinking water to model IBD. Colitis induction was confirmed by histopathology. Exploratory behavior was examined in the open field, associative memory by the novel-object recognition and Morris water maze tests, glymphatic clearance by in vivo two-photon imaging, and neuroinflammation by immunofluorescence and western blotting detection of inflammatory markers. Results Administration of DSS induced colitis, impaired spatial and recognition memory, activated microglia, and increased A1-like astrocyte numbers. In addition, DSS treatment impaired glymphatic clearance, aggravated amyloid plaque accumulation, and induced neuronal loss in the cortex and hippocampus. These neurodegenerative responses were associated with increased NLRP3 inflammasome expression and accumulation of gut-derived T lymphocytes along meningeal lymphatic vessels. Conversely, NLRP3 depletion protected against cognitive dysfunction, neuroinflammation, and neurological damage induced by DSS. Conclusions Colitis can exacerbate age-related neuropathology, while suppression of NLRP3 inflammasome activity may protect against these deleterious effects of colitis.

A high-temperature conductive silver slurry containing lead-free ZnO-B _2 O _3 -SiO _2 glass for metallization of ceramic MgTiO _3 substrate has been prepared. The ZnO-B _2 O _3 -SiO _2 glass was obtained by high-temperature melting and cold extraction with a transition temperature (T _g ) of 579 °C and thermal stability (∆T) of 105 °C as an inorganic bonding phase of high-temperature conductive silver paste. Then, silver paste with different glass powder content was sintered on ceramic MgTiO _3 substrate between 730 °C and 930 °C in increments of 50 °C. Characterization of the prepared materials revealed that their resistivity increases with the increase in glass powder content and decreases with the increase in sintering temperature. Sintering temperature and glass content have significant effects on the resistivity and adhesion of the thick silver film. When the silver paste with a glass content of 1.1 wt% was sintered at 830 °C for 10 min, the resulting thick silver film had a low resistivity of 1.81 μ Ω·cm (1.65 μ Ω·cm for silver) and a good adhesive strength of 39.4 N mm ^−2 . During the sintering process, the glass material melts and wets the silver powder, which promotes the sintering of the silver powder to form a dense network structure and improves the electrical conductivity of the silver film. In addition, the formation of ZnTiO _3 by chemical reactions between the glass and the substrate was observed, which dramatically improved the bonding strength of the silver film. Therefore, lead-free silver paste containing ZnO-B _2 O _3 -SiO _2 glass powder and MgTiO _3 ceramics has broad development prospects in ceramic filters.

The tumor microenvironment is essential for the formation and development of tumors. Cytokines in the microenvironment may affect the growth, metastasis and prognosis of tumors, and play different roles in different stages of tumors, of which transforming growth factor β (TGF-β) and tumor necrosis factor α (TNF-α) are critical. The two have synergistic and antagonistic effect on tumor regulation. The inhibition of TGF-β can promote the formation rate of tumor, while TGF-β can promote the malignancy of tumor. TNF-α was initially determined to be a natural immune serum mediator that can induce tumor hemorrhagic necrosis, it has a wide range of biological activities and can be used clinically as a target to immune diseases as well as tumors. However, there are few reports on the interaction between the two in the tumor microenvironment. This paper combs the biological effect of the two in different aspects of different tumors. We summarized the changes and clinical medication rules of the two in different tissue cells, hoping to provide a new idea for the clinical application of the two cytokines.

Pluripotent stem cells (PSCs) are characterized by their capacity for high self-renewal and multiple differentiation potential and include embryonic stem cells, embryonic germ cells and induced PSCs. PSCs provide a very suitable model for the studies of human diseases, drugs screening, regenerative medicine and developmental biology research. Pigs are considered as an ideal model for preclinical development of human xenotransplantation, therapeutic approaches and regenerative medicine because of their size and physiological similarity to humans. However, lack of knowledge about the derivation, characterization and pluripotency mechanisms of porcine PSCs hinders progress in these biotechnologies. In this review, we discuss the latest progress on porcine PSCs generation, evaluation criteria for pluripotency, the scientific and technical questions arising from these studies. We also introduce our perspectives on porcine PSC research, in the hope of providing new ideas for generating naive porcine PSCs and animal breeding.

Background and ObjectivesIn China, over 90% of esophageal cancer (EC) cases are esophageal squamous cell carcinoma (ESCC). ESCC is a frequently malignant tumor with poor prognosis despite the development of comprehensive therapeutic strategies, for which there is still a lack of effective prognostic factors. Previous studies found that the abnormal expression of TRPC1 is closely related to the proliferation, invasion, metastasis, and differentiation of various tumors. However, the relationship between TRPC1 and ESCC is currently unclear. The present study aimed to clarify the clinical significance of TRPC1 and to preliminarily assess the molecular mechanism by which TRPC1 regulates cell proliferation, migration, and invasion in ESCC.Materials and MethodsImmunohistochemistry (IHC) was used to determine the expression of TRPC1 and Ki-67 in 165 cases of ESCC. The correlations between TRPC1 expression and clinicopathological characteristics were determined, and both univariate and multivariate analyses were utilized to quantify the impact of TRPC1 expression on patient survival. Cell Counting Kit-8, scratch wound healing, and transwell assays were used to determine the effects of TRPC1 on proliferation, migration, and invasion in ESCC in vitro, respectively.ResultsThe positive expression rate of TRPC1 showed significantly decreased in ESCC (45.50%) compared with the levels in normal esophageal mucosa (NEM; 80.80%) and high-grade intraepithelial neoplasia (HGIEN; 63.20%) (P

Purpose This study was conducted to explore the effect of intervention in the form of sexual behavior guidance on the quality of sexual life of young and middle-aged male patients with rectal cancer. Methods Twenty cases of young and middle-aged male patients with rectal cancer were randomly divided into experimental and control group in each group including 10 cases per group. The control group was given the traditional health education after the rectal cancer Miles operation. While the experimental group was given sexual behavior guidance and “sex focused training therapy” after the Miles operation and before sexual intercourse in order to overcome erectile dysfunction. The International Index of Erectile Function (IIEF-5) questionnaire was used to measure the sexual functionality of both groups upon admission, at the time of discharge and after 3, 6 and 9 months. Results In the experimental group, patients with normal sexual function at the 6th and 9th month after discharge were 7 cases and 9 cases respectively, which were significantly higher than the control group which included 5 cases and 6 cases (p-value < 0.05). Conclusion In conclusion, sexual health education not only could effectively improve the sexual function of young and middle-aged male patients with rectal cancer after Miles operation, but also could improve the quality of the sexual life of the patients. It is considered to be worthy to promotion and application on clinical practice.

Although physical exercise is an effective strategy for treatment of ischemic stroke, the underlying protective mechanisms are still not well understood. It has been recently demonstrated that neural progenitor cells play a vital role in the recovery of neurological function (NF) through differentiation into mature neurons. In the current study, we observed that physical exercise significantly reduced the infarct size and improved damaged neural functional recovery after an ischemic stroke. Furthermore, we found that the treatment not only exhibited a significant increase in the number of neural progenitor cells and neurons but also decreased the apoptotic cells in the peri-infarct region, compared to a control in the absence of exercise. Importantly, the insulin-like growth factor-1 (IGF-1)/Akt signaling pathway was dramatically activated in the peri-infarct region of rats after physical exercise training. Therefore, our findings suggest that physical exercise directly influences the NF recovery process by increasing neural progenitor cell count via activation of the IGF-1/Akt signaling pathway.

Objective To investigate the clinical and pathological characteristics of sellar chondroid chordoma and discuss differential diagnosis of sellar chondroid chordoma with literature review. Methods The clinical manifestations of a patient with chondroid chordoma occurring in sellar area were stated. The morphological characteristics and immune phenotype were analyzed by using HE and immunohistochemical staining, and related literatures were reviewed. Results A 66-year-old male mainly presented with repeated hyponatremia. MRI revealed a well-circumscribed, round and space-occupying mass in sellar area. The tumor was removed under endoscope via the right nasal cavity. During the resection, the tumor could be seen locating in sellar region with solid, tough quality and clear boundaries. Histologically, part of the tumor showed the chondroid differentiation in classical chordoma. The immunohistochemistry of this tumor was positive for cytokeratin (CK), epithelial membrane antigen (EMA) and S-100 protein (S-100), and Ki-67 labeling index was about 1%. The pathological diagnosis was sellar chondroid chordoma. During the follow-up period of 11 months, the patient was in good condition and no tumor recurrence was found. Conclusions Despite low incidence, chondroid chordoma usually develops in the midline regions with distinctive histological features and immunohistochemical phenotypes. In general, the prognosis is better than general type of chordoma, and the diagnosis should be differentiated from general types of chordoma and chondrosarcoma.doi：10.3969/j.issn.1672-6731.2014.02.007

Genipin is the bioactive compound of geniposide and a natural cross-linking agent. In order to improve the preparation process of genipin, the hydrolysis of geniposide to genipin by immobilized β-glucosidase in an aqueous-organic two-phase system was studied. β-Glucosidase was immobilized by the crosslinking-embedding method using sodium alginate as the carrier. The optimum reaction temperature, pH value and time were 55 °C, 4.5 and 2.5 h, respectively. To reduce genipin hydrolysis and byproduct production the reaction was carried out in an aqueous-organic two-phase system comprising ethyl acetate and sodium acetate buffer. The product was analyzed by HPLC, UV, IR, and NMR. The yield of genipin was 47.81% and its purity was over 98% (HPLC).