Wuling capsule, composed of the traditional Chinese medicine Wuling mycelia powder, is made by fermenting and processing Xylaria nigripes (Kl.) Sacc. Clinically, it is commonly used to alleviate depression and anxiety. However, the mechanisms through which Wuling capsule exerts its therapeutic benefits have not been clearly defined.

AIM OF THE STUDY:

This study aims to elucidate the mechanisms by which Wuling capsule alleviates depression and anxiety like behaviors induced by chronic social defeat stress (CSDS) in mice.

MATERIALS AND METHODS:

High-performance liquid chromatography-tandem mass spectrometry system was used to identify the components of the Wuling capsule. Mice were subjected to CSDS to induce depression and anxiety-like behaviors. The expression of hypothalamic corticotropin-releasing hormone (CRH) and Nesfatin-1, as well as serum levels of adrenocorticotropic hormone (ACTH) and corticosterone (CORT) were quantified. Behavioral assessments included the open field test, elevated plus maze, sucrose preference test, and forced swim test to evaluate depression and anxiety levels. Specific manipulation of Nesfatin-1 in the paraventricular nucleus of the hypothalamus (PVN) or cells was achieved through stereotaxic virus injection or plasmid transfection. Intracerebral cannula implantation was used for PVN-specific drug administration.

RESULTS:

A total of 123 different components were identified in Wuling capsule. CSDS induced depression and anxiety-like behaviors in mice, along with hyperactivation of the HPA axis, increased hypothalamic Nesfatin-1 levels, and elevated nuclear factor kappa-B (NF-κB) phosphorylation. Overexpression of Nesfatin-1 in the hypothalamus mimicked the effects of CSDS. Conversely, knockdown of hypothalamic Nesfatin-1 or PVN-specific administration of Nesfatin-1 antibody or NF-κB antagonist mitigated CSDS-induced depression and anxiety-like behaviors and hypothalamic-pituitary-adrenal (HPA) axis hyperactivity. In neuroblastoma-2a (N2a) cells, overexpression of Nesfatin-1 led to increased NF-κB phosphorylation and CRH levels, whereas knockdown of Nesfatin-1 produced the opposite effects. Treatment with Wuling capsule alleviated CSDS-induced depression and anxiety-like behaviors, HPA axis hyperactivity, and activation of the hypothalamic Nesfatin-1/NF-κB pathway.

CONCLUSIONS:

The hypothalamic Nesfatin-1/NF-κB pathway plays a significant role in depression by modulating the HPA axis and is involved in the antidepressant and anxiolytic effects of Wuling capsule.

2025-01-01·TOXICOLOGY

Chronic exposure to polystyrene microplastics triggers osteoporosis by breaking the balance of osteoblast and osteoclast differentiation

Article

作者: Pan, Chun ; Fan, Zhencheng ; Hong, Runyang ; Chen, Hao ; Shi, Yujie ; Liu, Tingting ; Wang, Kehan

Plastic pollution is becoming more and more serious, and microplastics (MPs) formed by degradation from plastics significantly threaten the health of animals and humans. However, it remains unknown how MPs interfere with bone homeostasis by regulating the function of bone marrow mesenchymal stem cells (BMSCs). In order to simulate the toxic impacts of long-term low-dose MPs on the skeletal system, we constructed a 6-month drinking water model of mice exposed to MPs. We found that the bone microstructure in the femur of mice exposed to MPs was destroyed, the quantity of bone trabeculae decreased sharply and the bone mass decreased significantly, accompanied by the decrease of bone formation and the activation of osteoclasts. In addition, RNA sequencing showed NF-κB pathway was activated in MPs-treated BMSCs, manifested as significantly up-regulated inflammatory factors, accelerated the senescence of BMSCs, and inhibited their osteogenic differentiation and extracellular mineralization. Senescent BMSCs induced by MPs led to the overproduction of RANKL, which contributed to the production of more osteoclasts. Importantly, the administration of NF-κB inhibitors in vivo markedly diminished MPs-induced BMSCs senescence and impaired osteogenic differentiation. Meanwhile, the secretion of RANKL caused by MPs was reversed, and osteoclast formation was significantly reduced. In summary, our data innovatively reveal the core mechanism of MPs in bone balance. By promoting the NF-κB signaling pathway, it significantly accelerates the aging of BMSCs, causes a decrease in bone formation, and promotes osteoclast formation through RANKL.

2024-12-31·Animal Cells and Systems

AP001885.4 promotes the proliferation of esophageal squamous cell carcinoma cells by histone lactylation- and NF-κB (p65)-dependent transcription activation and METTL3-mediated mRNA stability of c-myc

Article

作者: Bai, Jie ; Tao, Hao ; Sun, Wen-Juan ; Yu, Bin-Bing ; Hao, Jia-Jie ; Song, Sheng-Jie ; Li, Wen-Ting ; Jiang, Wen ; Jin, Xin ; Zhang, Xin-Guo ; Wang, Chong ; Shi, Zhi-Zhou ; Fu, Chuang

Esophageal squamous cell carcinoma (ESCC) is an aggressive malignant neoplasm, and up to now, the role of long non-coding RNA (lncRNA) AP001885.4 in cancer, including ESCC, is absolutely unclear. The GEPIA database was applied to identify differentially expressed and prognosis-associated genes in esophageal cancer (ESCA). CCK-8, colony formation, Western blot, and qRT-PCR methods were harnessed to investigate the role and mechanism of AP001885.4 in esophageal carcinogenesis. By analyzing TCGA data in the GEPIA database, two lncRNAs were selected. AP001885.4 was overexpressed and positively associated with the unfavorable outcome of ESCC patients, and LINC001786 was under-expressed and negatively linked with the poor prognosis. Knockdown of AP001885.4 suppressed the proliferation and colony formation of ESCC cells. Importantly, the silence of AP001885.4 downregulated c-myc. Mechanically, the knockdown of AP001885.4 reduced METTL3 expression and m6A modification in c-myc mRNA, and METTL3 positively regulated c-myc. Furthermore, the knockdown of AP001885.4 diminished histone lactylation and NF-κB (p65) expression, and the protein lactylation inhibitors (2-DG, 2-deoxy-D-glucose and oxamate) and the NF-κB inhibitor (JSH-23) also lessened c-myc expression. Consequently, our findings suggested that AP001885.4 promoted the proliferation of esophageal squamous cell carcinoma cells by histone lactylation- and NF-κB (p65)-dependent transcription activation and METTL3-mediated mRNA stability of c-myc.

项与 NF-κB inhibitors(China Pharmaceutical University) 相关的新闻（医药）

2024-04-18

·GlobeNewswire-Health Care

BioVie to Present Data Showing How NE3107 Potentially Restores Homeostasis via Specific Genes Associated with Dementia, Metabolism, and Inflammation

Additionally, the Company announced approval of the non-proprietary name “bezisterim” for NE3107CARSON CITY, Nev., April 18, 2024 (GLOBE NEWSWIRE) -- BioVie Inc. (Nasdaq: BIVI), (“BioVie” or the “Company”), a clinical-stage company developing innovative drug therapies for the treatment of neurological and neurodegenerative disorders and advanced liver disease, today announced that an oral presentation and poster presentation will be shared at the 12th Annual Alzheimer's & Parkinson's Drug Development Summit to be held in Boston, Massachusetts April 23-25. Additionally, the United States Adopted Names (USAN) Council, and the World Health Organization (WHO) International Nonproprietary Names (INN) expert committee has approved “bezisterim” as the non-proprietary (generic) name for NE3107, an orally active partial NF-κB inhibitor product candidate being studied in Parkinson’s Disease and Alzheimer’s Disease. The oral and poster presentations 12th Annual Alzheimer's & Parkinson's Drug Development Summit will provide additional details on how bezisterim appears to have an impact on DNA methylation on 5 different “clocks” measuring biological age and that the extent of DNA methylation is correlated to a series of clinical measures. The oral presentation titled “Clinical Outcomes and Biomarker Findings from a Randomized, Placebo-Controlled Trial of NE3107 in Subjects with Mild to Moderate Probably Alzheimer’s Disease” will be presented by Christopher L. Reading, BioVie’s Senior Vice President, Alzheimer’s Disease Program, on Wednesday, April 24 at 2:30 p.m. EDT. The poster with the same title will be presented at 6:45 p.m. on the same day. Details of the presented data and conclusions will be announced once the presentations are made public at the conference. About BioVie Inc.BioVie Inc. (NASDAQ: BIVI) is a clinical-stage company developing innovative drug therapies for the treatment of neurological and neurodegenerative disorders and advanced liver disease. In neurodegenerative disease, the Company’s drug candidate bezisterim inhibits inflammatory activation of ERK and NFkB (e.g., TNF signaling) that leads to neuroinflammation and insulin resistance, but not their homeostatic functions (e.g., insulin signaling and neuron growth and survival). Both are drivers of Alzheimer’s and Parkinson’s diseases. The Company conducted and reported efficacy data on its randomized, double-blind, placebo-controlled, parallel-group, multicenter study to evaluate bezisterim in patients who have mild to moderate Alzheimer's disease (NCT04669028). Results of a Phase 2 investigator-initiated trial (NCT05227820) showing bezisterim-treated patients experienced improved cognition and biomarker levels were presented at the Clinical Trial in Alzheimer’s Disease annual conference in December 2022. An estimated six million Americans suffer from Alzheimer’s. A Phase 2 study of bezisterim in Parkinson’s disease (NCT05083260) has completed, and data presented at the International Conference on Alzheimer's and Parkinson's Disease and Related Neurological Disorders conference in Gothenburg, Sweden in March 2023 showed significant improvements in “morning on” symptoms and clinically meaningful improvement in motor control in patients treated with a combination of bezisterim and levodopa vs. patients treated with levodopa alone, and no drug-related adverse events. In liver disease, the Company’s Orphan drug candidate BIV201 (continuous infusion terlipressin), with U.S Food and Drug Administration (“FDA”) Fast Track status, is being evaluated and discussed with guidance received from the FDA regarding the design of Phase 3 clinical testing of BIV201 for the treatment of ascites due to chronic liver cirrhosis. The active agent is approved in the U.S. and in about 40 countries for related complications of advanced liver cirrhosis. For more information, visit http://www.bioviepharma.com/. Forward-Looking StatementsThis press release contains forward-looking statements, which may be identified by words such as "expect," "look forward to," "anticipate" "intend," "plan," "believe," "seek," "estimate," "will," "project" or words of similar meaning. Although BioVie Inc. believes such forward-looking statements are based on reasonable assumptions, it can give no assurance that its expectations will be attained. Actual results may vary materially from those expressed or implied by the statements herein due to the Company's ability to successfully raise sufficient capital on reasonable terms or at all, available cash on hand and contractual and statutory limitations that could impair our ability to pay future dividends, our ability to complete our pre-clinical or clinical studies and to obtain approval for our product candidates, our ability to successfully defend potential future litigation, changes in local or national economic conditions as well as various additional risks, many of which are now unknown and generally out of the Company's control, and which are detailed from time to time in reports filed by the Company with the SEC, including quarterly reports on Form 10-Q, reports on Form 8-K and annual reports on Form 10-K. BioVie Inc. does not undertake any duty to update any statements contained herein (including any forward-looking statements), except as required by law. For Investor Relations Inquiries:Bruce MackleManaging Director, LifeSci Advisors, LLCbmackle@lifesciadvisors.com For Media Relations Inquiries:Melyssa WeibleManaging Partner, Elixir Health Public Relationsmweible@elixirhealthpr.com

临床2期孤儿药临床结果快速通道上市批准

100 项与 NF-κB inhibitors(China Pharmaceutical University) 相关的药物交易

登录后查看更多信息