Synthesis and antiproliferative evaluation of new hybrids of piperine and acylhydrazone.

Piperine, a natural amide isolated from the genus of Piper, serves as a pharmacophore in medicinal chemistry. In this study, we synthesised and evaluated 18 novel piperine-acylhydrazone hybrids (4a-4r) for their antiproliferative activities in vitro. The structures of these hybrids were validated using 1H,13C NMR, and HR-ESI-MS data. Furthermore, we screened all synthesised compounds for their antiproliferative activities against three human cancer cell lines: FaDu (laryngeal carcinoma cells), HepG2 (hepatoblastoma carcinoma cells), and MGC803 (gastric carcinoma cells). Among them, compound 4o exhibited significantly inhibitory activities against FaDu, HepG2, and MGC803 with IC50 values of 13.85 ± 0.19, 11.02 ± 1.45, and 13.47 ± 3.43 µM, respectively, which was approximately two-fold lower than the positive control cisplatin. These findings suggest that compound 4o has the potential to be promising leads for the design of anti-cancer drugs.

Notes on the Pselaphodes Westwood complex (Coleoptera, Staphylinidae, Pselaphinae) of Hubei, China, with description of a new species and additional faunistic data.

The Pselaphodes Westwood complex of genera is represented in Hubei Province by four genera and eight species. Recent field work at Wanchaoshan Nature Reserve, Xingshan County revealed a small series of material belonging to this complex. In this paper, we describe Pselaphodeswanchaoshanus sp. nov. and provide new faunistic data for P.nomurai Yin, Li & Zhao. A key to the hitherto known members of Pselaphodes complex that occur in Hubei is provided to facilitate ready species identification.

Efficacy and safety of acupuncture for postpartum hypogalactia: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Postpartum hypogalactia (PH) is prominent during lactation and may negatively impact the mother's or infant's health. Acupuncture is widely used to increase maternal breast milk production. However, the effects of acupuncture on PH remain unclear. Therefore, this review aimed to evaluate the efficacy and safety of acupuncture in individuals with PH. MATERIALS AND METHODS: Articles on potentially eligible randomized controlled trials (RCTs) on acupuncture for PH published from database inception to October 2023 were retrieved from the PubMed, Web of Science, Cochrane Library, EMBASE, EBSCO, Scopus, China National Knowledge Infrastructure, Chinese Biomedical Literature Database, WanFang, and VIP databases. Two reviewers independently screened the records, extracted essential information, and evaluated the methodological quality of the RCTs using the revised Cochrane risk-of-bias (RoB) tool. The primary outcome was a change in serum prolactin (PRL) levels before and after treatment. Secondary outcomes included milk secretion volume (MSV), total effective rate (TER), mammary fullness degree (MFD), and exclusive breastfeeding rate (EBR). Meta-analyses were performed using RevMan v5.4. Finally, the quality of evidence was evaluated using the Grading of Recommendations, Assessment, Development, and Evaluation tool. RESULTS: This study included 19 RCTs involving 2,400 participants. The included studies were classified as having an unclear to high RoB. Our findings indicated that, overall, acupuncture showed a significant effect in increasing serum PRL levels (standardized mean differences [SMDs] = 1.09, 95% confidence interval [CI]: 0.50, 1.68), MSV (SMD = 1.69, 95% CI: 0.53, 2.86), TER (relative risk [RR] = 1.25, 95% CI: 1.10, 1.42), and EBR (RR = 2.01, 95% CI: 1.07, 3.78) compared to that in the control group; however, no difference in MFD (SMD = 1.17, 95% CI: -0.09, 2.42) was observed. In the subgroup analysis, acupuncture combined with Chinese herbs or conventional treatment was significantly more effective in increasing serum PRL levels, MSV, and TER than did Chinese herbs or conventional treatment alone. Moreover, acupuncture alone resulted in significantly higher serum PRL levels compared to Chinese herbs; however, this benefit was not observed for TER and MFD. The quality of evidence was critically low. CONCLUSION: Acupuncture may effectively increase milk secretion in women with PH. However, owing to the low quality of evidence, further rigorously designed studies are warranted to confirm our findings.

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In this study, we explored the changes in plant community diversity and their relationship with soil factors under shrub encroachment pressure by selecting four marsh areas in Sanjiang Plain with different degrees of shrub cover (a, 0≤a≤100%), including marsh with no shrub encroachment (a=0), light shrub encroachment (0

Ganoderic acid A ameliorates depressive-like behaviors in CSDS mice: Insights from proteomic profiling and molecular mechanisms.

OBJECTIVE: Ganoderic Acid A (GAA), a primary bioactive component in Ganoderma, has demonstrated ameliorative effects on depressive-like behaviors in a Chronic Social Defeat Stress (CSDS) mouse model. This study aims to elucidate the underlying molecular mechanisms through proteomic analysis. METHODS: C57BL/6 J mice were allocated into control (CON), chronic social defeat stress (CSDS), GAA, and imipramine (IMI) groups. Post-depression induction via CSDS, the GAA and IMI groups received respective treatments of GAA (2.5 mg/kg) and imipramine (10 mg/kg) for five days. Behavioral assessments utilized standardized tests. Proteins from the prefrontal cortex were analyzed using LC-MS, with further examination via bioinformatics and PRM for differential expression. Western blot analysis confirmed protein expression levels. RESULTS: Chronic social defeat stress (CSDS) induced depressive-like behaviors in mice, which were significantly alleviated by GAA treatment, comparably to imipramine (IMI). Proteomic analysis identified distinct proteins in control (305), GAA-treated (949), and IMI-treated (289) groups. Enrichment in mitochondrial and synaptic proteins was evident from GO and PPI analyses. PRM analysis revealed significant expression changes in proteins crucial for mitochondrial and synaptic functions (namely, Naa30, Bnip1, Tubgcp4, Atxn3, Carmil1, Nup37, Apoh, Mrpl42, Tprkb, Acbd5, Dcx, Erbb4, Ppp1r2, Fam3c, Rnf112, and Cep41). Western blot validation in the prefrontal cortex showed increased levels of Mrpl42, Dcx, Fam3c, Ppp1r2, Rnf112, and Naa30 following GAA treatment. CONCLUSION: GAA exhibits potential antidepressant properties, with its action potentially tied to the modulation of synaptic functions and mitochondrial activities.

Research status and trends of physical activity on depression or anxiety: a bibliometric analysis.

Background: Anxiety and depression are prevalent mental disorders. As modern society continues to face mounting pressures, the incidence of anxiety and depression is on the rise. In recent years, there has been an increasing breadth of research exploring the relationship between anxiety, depression, and physical activity (PA). However, the current research progress and future development trends are unclear. The purpose of this study is to explore the research hotspots and development trends in this field, and to provide guidance for future studies and to provide some reference for clinicians. Methods: We searched the relevant literature of Web of Science Core Collection from the establishment of the database to August 15, 2023. CiteSpace, VOSviewer and Bibliometrix Packages based on the R language were used to analyze the number of publications, countries, institutions, journals, authors, references, and keywords. Results: A total of 1,591 studies were included in the analysis, and the research in the field of PA on anxiety or depression has consistently expanded. The USA (304 publications), Harvard University (93 publications), and the journal of affective disorders (97 publications) were the countries, institutions, and journals that published the highest number of articles, respectively. According to the keywords, students and pregnant women, adult neurogenesis, and Tai Chi were the groups of concern, physiological and pathological mechanisms, and the type of PA of interest, respectively. Conclusion: The study of PA on anxiety or depression is experiencing ongoing expansion. Clinicians can consider advising patients to take mind-body exercise to improve mood. In addition, future researchers can explore the mind-body exercise and its impact on anxiety or depression, PA and anxiety or depression in specific populations, and adult neurogenesis of various exercise in anxiety or depression.

Hydroxychloroquine-induced pigmentation in rheumatic diseases: prevalence, clinical features and influencing factors.

OBJECTIVE: To describe the clinical features of Chinese patients with hydroxychloroquine (HCQ)-induced pigmentation and analyze the potential risk factors associated with HCQ-induced pigmentation. METHODS: A cross-sectional study was conducted over a duration of 7 months, during which patients who had received HCQ treatment for >6 months were included. Data was collected through a structured questionnaire that encompassed demographic and geographic characteristics, information on HCQ and concomitant medication usage, sun exposure characteristics, and hyperpigmentation-related characteristics. Univariate and multivariate analyses were employed to calculate the statistical association between HCQ-induced pigmentation and multiple variables. RESULTS: Out of 316 patients, 83 (26.3%) patients presented hyperpigmentation during HCQ treatment. Hyperpigmentation presented after a median duration of HCQ treatment of 12 months (interquartile range, 6.0 months-30.0 months) with a median cumulative dose of 108 g of HCQ (interquartile range, 36-288 g). The most frequently affected sites of pigmentation were the face (60.2%), lower limbs (36.1%), and hands (20.5%). There was a linear decrease in the incidence of pigmentation with increasing daily sun exposure time (p= 0.030). In the multivariate analysis, variables (cumulative HCQ dose and daily sun exposure time) were included in the final models. The results revealed an independent correlation between HCQ-induced pigmentation and daily sun exposure exceeding 1 h (OR: 0.431; 95%CI: 0.208-0.892; p= 0.023). CONCLUSIONS: The occurrence of HCQ-induced pigmentation is not uncommon, with an incidence rate of 26.3%. Daily sun exposure time exhibited a protective effect against HCQ-induced pigmentation.

Supplements for cognitive ability in patients with mild cognitive impairment or Alzheimer's disease: a protocol for systematic review and network meta-analysis of randomised controlled trials.

INTRODUCTION: Considering the increasing incidence of Alzheimer's disease (AD) and mild cognitive impairment (MCI) worldwide, there is an urgent need to identify efficacious, safe and convenient treatments. Numerous investigations have been conducted on the use of supplements in this domain, with oral supplementation emerging as a viable therapeutic approach for AD or MCI. Nevertheless, given the multitude of available supplements, it becomes imperative to identify the optimal treatment regimen. METHODS AND ANALYSIS: Eight academic databases and three clinical trial registries will be searched from their inception to 1 June 2023. To identify randomised controlled trials investigating the effects of supplements on patients with AD or MCI, two independent reviewers (X-YZ and Y-QL) will extract relevant information from eligible articles, while the risk of bias in the included studies will be assessed using the Rob 2.0 tool developed by the Cochrane Collaboration. The primary outcome of interest is the overall cognitive function. Pair-wise meta-analysis will be conducted using RevMan V.5.3, while network meta-analysis will be carried out using Stata 17.0 and ADDIS 1.16.8. Heterogeneity test, data synthesis and subgroup analysis will be performed if necessary. The GRADE system will be employed to assess the quality of evidence. This study is scheduled to commence on 1 June 2023 and conclude on 1 October 2023. ETHICS AND DISSEMINATION: Ethics approval is not required for systematic review and network meta-analysis. The results will be submitted to a peer-reviewed journal or at a conference. TRIAL REGISTRATION NUMBER: PROSPERO (CRD42023414700).

Possible potential spread of Anopheles stephensi, the Asian malaria vector.

BACKGROUND: Anopheles stephensi is native to Southeast Asia and the Arabian Peninsula and has emerged as an effective and invasive malaria vector. Since invasion was reported in Djibouti in 2012, the global invasion range of An. stephensi has been expanding, and its high adaptability to the environment and the ongoing development of drug resistance have created new challenges for malaria control. Climate change is an important factor affecting the distribution and transfer of species, and understanding the distribution of An. stephensi is an important part of malaria control measures, including vector control. METHODS: In this study, we collected existing distribution data for An. stephensi, and based on the SSP1-2.6 future climate data, we used the Biomod2 package in R Studio through the use of multiple different model methods such as maximum entropy models (MAXENT) and random forest (RF) in this study to map the predicted global An. stephensi climatically suitable areas. RESULTS: According to the predictions of this study, some areas where there are no current records of An. stephensi, showed significant areas of climatically suitable for An. stephensi. In addition, the global climatically suitability areas for An. stephensi are expanding with global climate change, with some areas changing from unsuitable to suitable, suggesting a greater risk of invasion of An. stephensi in these areas, with the attendant possibility of a resurgence of malaria, as has been the case in Djibouti. CONCLUSIONS: This study provides evidence for the possible invasion and expansion of An. stephensi and serves as a reference for the optimization of targeted monitoring and control strategies for this malaria vector in potential invasion risk areas.

piRNA loading triggers MIWI translocation from the intermitochondrial cement to chromatoid body during mouse spermatogenesis.

The intermitochondrial cement (IMC) and chromatoid body (CB) are posited as central sites for piRNA activity in mice, with MIWI initially assembling in the IMC for piRNA processing before translocating to the CB for functional deployment. The regulatory mechanism underpinning MIWI translocation, however, has remained elusive. We unveil that piRNA loading is the trigger for MIWI translocation from the IMC to CB. Mechanistically, piRNA loading facilitates MIWI release from the IMC by weakening its ties with the mitochondria-anchored TDRKH. This, in turn, enables arginine methylation of MIWI, augmenting its binding affinity for TDRD6 and ensuring its integration within the CB. Notably, loss of piRNA-loading ability causes MIWI entrapment in the IMC and its destabilization in male germ cells, leading to defective spermatogenesis and male infertility in mice. Collectively, our findings establish the critical role of piRNA loading in MIWI translocation during spermatogenesis, offering new insights into piRNA biology in mammals.

The effect of artificial light at night (ALAN) on the characteristics of diapause of Aedes albopictus.

BACKGROUND: Recently, the effect of artificial light at night (ALAN) on the physiology and behavior of insects has gradually attracted the attention of researchers and has become a new research topic. Aedes albopictus is an important vector that poses a great public health risk. Further studies on the diapause of Ae. albopictus can provide a basis for new vector control, and it is also worth exploring whether the effect of ALAN on the diapause of Ae. albopictus will provide a reference for the prevention and control of infectious diseases mediated by Ae. albopictus. METHODS: In this study, we experimentally studied the diapause characteristics of different geographical strains of Ae. albopictus under the interference of ALAN, explored the effect of ALAN on the diapause of Ae. albopictus and explored the molecular mechanism of ALAN on the diapause process through RNA-seq. RESULTS: As seen from the diapause incidence, Ae. albopictus of the same geographic strain showed a lower diapause incidence when exposed to ALAN. The differentially expressed genes (DEGs) were mainly enriched in signaling and metabolism-related pathways in the parental females and diapause eggs of the ALAN group. CONCLUSIONS: ALAN inhibits Ae. albopictus diapause. In the short photoperiod induced diapause of Ae. albopictus in temperate strain Beijing and subtropical strain Guangzhou, the disturbance of ALAN reduced the egg diapause rate and increased the egg hatching rate of Ae. albopictus, and the disturbance of ALAN also shortened the life cycle of Ae. albopictus eggs after hatching.

Two new species of ant-loving beetles (Coleoptera: Staphylinidae: Pselaphinae) from Jiulong National Wetland Park, China.

Continued collecting efforts at the Jiulong National Wetland Park, Zhejiang, East China revealed two additional species of the ant-loving beetle subfamily Pselaphinae (Coleoptera: Staphylinidae): Trisiniotus jiulong sp. nov. and Arthromelodes lianghongbini sp. nov. Both new species are diagnosed, described, and their important characters are illustrated.

Description of a new species of the genus Woznessenskia from Xizang, China (Orthoptera: Gryllacrididae).

The gryllacridid genus Woznessenskia Gorochov, 2002 comprises 13 extant species from Asia, with 8 species reported from China and 5 species reported from Vietnam. A new species from Xizang, China, Woznessenskia lianhua sp. nov., is reported in this paper.

Short-term effects of cupping and scraping therapy for chronic nonspecific low-back pain: A prospective, multicenter randomized trial.

BACKGROUND: As one of the most common musculoskeletal ailments, chronic nonspecific low-back pain (CNLBP) causes persistent disability and substantial medical expenses. Epidemiological evidence shows that the incidence rate of CNLBP in young and middle-aged people who are demanded rapidly recovery and social contribution is rising. Recent guidelines indicate a reduced role for medicines in the management of CNLBP. OBJECTIVE: The present study investigates the short-term effects of cupping and scraping therapy using a medicated balm, compared to nonsteroidal anti-inflammatory drug (NSAID) with a capsaicin plaster, in the treatment of CNLBP. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: We designed a prospective multicenter randomized clinical trial enrolling patients from January 1, 2022 to December 31, 2022. A total of 156 patients with CNLBP were randomized into two parallel groups. Diclofenac sodium-sustained release tablets were administered orally to participants in the control group for one week while a capsaicin plaster was applied externally. Patients in the test group were treated with cupping and scraping using a medical device and medicated balm. MAIN OUTCOME MEASURES: Primary outcome was pain recorded using the visual analogue scale (VAS). Two secondary outcomes were recorded using the Japanese Orthopedic Association low-back pain scale (JOA) and the traditional Chinese medicine (TCM) syndrome integral scale (TCMS) as assessment tools. RESULTS: Between baseline and postintervention, all changes in outcome metric scales were statistically significant (P < 0.001). Compared to the control group, patients in the test group had a significantly greater treatment effect in all outcome variables, as indicated by lower VAS and TCMS scores and higher JOA scores, after the one-week intervention period (P < 0.001). Further, according to the findings of multivariate linear regression analysis, the participants' pain (VAS score) was related to their marital status, age, smoking habits and body mass index. No adverse reactions were reported for any participants in this trial. CONCLUSION: The effectiveness of TCM combined with the new physiotherapy tool is superior to that of NSAID combined with topical plasters, regarding to pain intensity, TCM symptoms and quality of life. The TCM plus physiotherapy also showed more stable and long-lasting therapeutic effects. TRIAL REGISTRATION: This study was registered at Chinese Clinical Trial Registry (ChiCTR2200055655). Please cite this article as: He JY, Tu XY, Yin ZF, Mu H, Luo MJ, Chen XY, Cai WB, Zhao X, Peng C, Fang FF, Lü C, Li B. Short-term effects of cupping and scraping therapy for chronic nonspecific low-back pain: A prospective, multicenter randomized trial. J Integr Med. 2024; 22(1): 39-45.

Inhibition of PI3K/AKT signaling pathway prevents blood-induced heterotopic ossification of the injured tendon.

Objective: It is a common clinical phenomenon that blood infiltrates into the injured tendon caused by sports injuries, accidental injuries, and surgery. However, the role of blood infiltration into the injured tendon has not been investigated. Methods: A blood-induced rat model was established and the impact of blood infiltration on inflammation and HO of the injured tendon was assessed. Cell adhesion, viability, apoptosis, and gene expression were measured to evaluate the effect of blood treatment on tendon stem/progenitor cells (TSPCs). Then RNA-seq was used to assess transcriptomic changes in tendons in a blood infiltration environment. At last, the small molecule drug PI3K inhibitor LY294002 was used for in vivo and in vitro HO treatment. Results: Blood caused acute inflammation in the short term and more severe HO in the long term. Then we found that blood treatment increased cell apoptosis and decreased cell adhesion and tenonic gene expression of TSPCs. Furthermore, blood treatment promoted osteochondrogenic differentiation of TSPCs. Next, we used RNA-seq to find that the PI3K/AKT signaling pathway was activated in blood-treated tendon tissues. By inhibiting PI3K with a small molecule drug LY294002, the expression of osteochondrogenic genes was markedly downregulated while the expression of tenonic genes was significantly upregulated. At last, we also found that LY294002 treatment significantly reduced the tendon HO in the rat blood-induced model. Conclusion: Our findings indicate that the upregulated PI3K/AKT signaling pathway is implicated in the aggravation of tendon HO. Therefore, inhibitors targeting the PI3K/AKT pathway would be a promising approach to treat blood-induced tendon HO.

Eutypellaolides A-J, Sesquiterpene diversity expansion of the polar fungus Eutypella sp. D-1.

Eight new 12,8-eudesmanolide sesquiterpenes, eutypellaolides A-H (1-8), and two new eudesmane-type sesquiterpenes, eutypellaolides I-J (9-10), along with four known 12,8-eudesmanolide compounds 11-14, were isolated from the culture extract of the polar fungus Eutypella sp. D-1 by one strain many compounds (OSMAC) approach. The structures of these compounds were determined through comprehensive spectroscopic data and experimental and calculated ECD analysis. Antibacterial, immunosuppressive, and PTP1B inhibition activities of these compounds were evaluated. Compounds 1 and 11 exhibited strong inhibitory activities against Bacillus subtilis and Staphylococcus aureus, with each showing an MIC value of 2 µg/mL. Compound 9 displayed weak immunosuppressive activity against ConA-induced T-cell proliferation with an inhibitory rate of 61.7% at a concentration of 19.8 µM. Compounds 5, 11, and 14 exhibited weak PTP1B inhibition activities with IC50 values of 44.8, 43.2, and 49.5 µM, respectively.

The effect of acupuncture on oxidative stress in animal models of vascular dementia: a systematic review and meta-analysis.

BACKGROUND: Growing evidence showed that acupuncture may improve cognitive function by reducing oxidative stress, key to the pathogenesis in vascular dementia (VaD), but this is yet to be systematically analysed. This study aimed to summarize and evaluate the effect of acupuncture on oxidative stress in animal models of VaD. METHOD: Eight databases including PubMed, Embase, Web of Science, Cochrane library, CNKI, Wan Fang, CBM, and VIP were searched since their establishment until April 2023, for studies that reported the effect of acupuncture on oxidative stress in VaD animal models. Relevant literature was screened, and information was extracted by two reviewers. The primary outcomes were the levels of oxidative stress indicators. The methodological quality was assessed via the SYRCLE Risk of Bias Tool. Statistical analyses were performed using the RevMan and Stata software. RESULTS: In total, 22 studies with 747 animals were included. The methodology of most studies had flaws or uncertainties. The meta-analysis indicated that, overall, acupuncture significantly reduced the expression of pro-oxidants including reactive oxygen species (standardized mean differences [SMDs] = -4.29, 95% confidence interval [CI]: -6.26, -2.31), malondialdehyde (SMD = -2.27, 95% CI: -3.07, -1.47), nitric oxide (SMD = -0.85, 95% CI: -1.50, -0.20), and nitric oxide synthase (SMD = -1.01, 95% CI: -1.69, -0.34) and enhanced the levels of anti-oxidants including super oxide dismutase (SMD = 2.80, 95% CI: 1.98, 3.61), glutathione peroxidase (SMD = 1.32, 95% CI: -0.11, 2.76), and catalase (SMD = 1.31, 95% CI: 0.05, 2.58) in VaD animal models. In subgroup analyses, acupuncture showed significant effects on most variables. Only partial modelling methods and treatment duration could interpret the heterogeneity of some outcomes. CONCLUSION: Acupuncture may inhibit oxidative stress to improve cognitive deficits in animal models of VaD. Nevertheless, the methodological quality is unsatisfactory. More high-quality research with a rigorous design and further experimental researches and clinical trials are needed to confirm these findings. SYSTEMATIC REVIEW REGISTRATION: This study was registered in PROSPERO (CRD42023411720).

The role and mechanism of miR-425-3p regulating neuronal pyroptosis -mediated inorganic arsenic-induced generalized anxiety disorder.

Pyroptosis plays a critical role in the pathogenesis of mental disorders. However, its specific role and mechanism in arsenic (As)-induced generalized anxiety disorder (GAD) remain elusive. We utilized the data from CtdBbase, Phenopedia and DisGeNet to analyze genes that interact with arsenic poisoning and GAD. Subsequently KEGG and GO enrichment analysis were conducted to preliminatively predict the mechanism of inorganic arsenic-induced GAD. Male Wistar rats were administered water containing NaAsO2 (50, 100 µg/L) to evaluate GAD-like behavior through open field test and elevated plus maze. The expression of differential miRNAs including miR-425-3p, and pyroptosis in the prefrontal cortex of rats were detected. Furthermore, SKNSH cells were stimulated with NaAsO2 to examine the molecular changes, and then miR-425-3p mimic was transfected into SKNSH cells to detect pyroptosis in order to verify the function of miR-425-3p. Inorganic arsenic was confirmed to induce GAD-like behavior in rats, characterized by decreased locomotor activity and exploratory activities. Rats with inorganic arsenic-induced GAD exhibited reduced miR-425-3p expression levels in the prefrontal cortex and increased expression of pyroptosis-related proteins, including NF-κB, NLRP3, Caspase-1, GSDMD, IL-1ß, and IL-18. Treating with different concentrations of NaAsO2 showed that inorganic arsenic exposure downregulates miR-425-3p expression in SKNSH cells and upregulates the expression levels of pyroptosis-related proteins. Dual-luciferase reporter gene experiments demonstrated that miR-425-3p targets the NFKB1. Overexpressing miR-425-3p reversed the inorganic arsenic-induced pyroptosis in SKNSH cells by inhibiting the expression of NF-κB, NLRP3, Caspase-1, GSDMD, IL-1ß, and IL-18. Our findings suggest that inorganic arsenic exposure may induce GAD-like behavior in rats by downregulating miR-425-3p in prefrontal cortex, which targets NF-κB and regulates pyroptosis in neuronal cells.

Application of serum peptidomics for Parkinson's disease in SNCA-A30P mice.

Intraneuronal inclusions of alpha-synuclein (α-synuclein, α-syn) are commonly found in the brain of patients with Parkinson's disease (PD). The pathogenesis of the abundant α-syn protein in the blood has been extensively studied to understand its properties better. In recent years, peptidome analysis has received increasing attention. In this study, we identified and analyzed serum peptides from wild-type (WT) and the (Thy-1)-h[A30P] alpha-synuclein transgenic mice (SNCA-A30P mice) using liquid chromatography-tandem mass spectrometry (LC-MS/MS). One thousand eight hundred fifty-six peptides from 771 proteins were analyzed. Among them, 151 peptides from 107 proteins were significantly differentially expressed. The glycoprotein VI platelet pathway (GP6) was the pathway's most significant differentially expressed signaling pathway. Cleavage sites of the differentially expressed peptides may reflect protease distribution and activity. We selected the most significantly differentially expressed peptide, VGGDPI, and found that it contained cathepsin K (Ctsk) and trypsin-1 cleavage sites, suggesting that Ctsk and trypsin-1 may be key peptidases in PD. α-syn is a protein associated with the pathogenesis of PD. mutations in several genes, including SNCA, which encodes α-syn, are associated with the development of PD. Bioinformatics analysis of the physiological pathways related to SNCA genes and apoptosis genes found the five most markedly up-regulated proteins: formin homology 2 domain-containing 1 (FHOD1), insulin receptor substrate 1(IRS1), TRPM8 channel-associated factor 1 (TCAF1), glyceraldehyde 3-phosphate dehydrogenase (GAPDH), and interleukin-16 (IL-16). Therefore, the differentially expressed peptides in the five precursor protein domains may be potential bioactive peptides associated with α-syn and apoptosis. This study provides a validated peptidomics profile of SNCA-A30P mice and identifies potentially bioactive peptides linked to α-syn and apoptosis.