Kegang Linghu

Background: Glioblastoma is one of the most aggressive and lethal forms of brain cancer, characterized by rapid angiogenesis and infiltration of tumor-associated macrophages in the tumor microenvironment (TME). Given the limited efficacy of single-targeting tumor cell therapies against glioblastoma, regulating the TME has emerged as a promising strategy to improve therapeutic outcomes. Materials and methods: The Cancer Genome Atlas (TCGA) was used to assess the association between ligand-dependent nuclear receptor corepressor (LCoR) expression and glioblastoma. LCoR expression in patient glioma specimens was examined by qRT‑PCR and Western blot. LCoR was knocked down or overexpressed in glioblastoma cell lines (SF295, SNB19) using lentiviral vectors, followed by functional assays for proliferation, migration, invasion, angiogenesis, chemokine secretion, and monocyte migration. Subcutaneous and orthotopic mouse models were established to evaluate tumor growth, angiogenesis, and macrophage infiltration via immunohistochemistry and immunofluorescence. Transcriptome sequencing was performed on LCoR‑overexpressing cells to explore underlying mechanisms. In addition, mice were treated with the small-molecule compound deoxynyboquinone to assess its therapeutic effect via LCoR‑mediated regulation. Results: TCGA analysis reveals lower LCoR expression in glioblastoma than in normal tissues, correlating with improved patient survival. Clinical samples further confirm reduced LCoR expression in tumor versus peri-tumor tissues. LCoR knockdown significantly enhanced the proliferation, migration, and invasion of glioblastoma cells, whereas LCoR overexpression inhibited these malignant phenotypes. Mechanistically, LCoR suppressed VEGF and HIF-1α expression in tumor cells, thereby reducing angiogenesis and tumor sphere formation. Transcriptome sequencing revealed that LCoR is involved in immune regulation. Further experiments demonstrated that LCoR inhibited chemokine secretion, thereby reducing monocyte migration and macrophage M2 polarization. In subcutaneous and orthotopic glioblastoma mouse models, LCoR overexpression suppressed tumor growth by inhibiting angiogenesis and macrophage M2 polarization. Treatment with the deoxynyboquinone reduced angiogenesis and macrophage infiltration in the TME through LCoR-mediated downregulation of MCP-1, thereby blocking glioblastoma progression. Conclusion: LCoR serves as a potential therapeutic target against glioblastoma. Upregulating LCoR can inhibit glioblastoma development by suppressing angiogenesis and immune evasion within the TME.

Chronic liver fibrosis remains a major healthcare burden with no approved pharmacotherapies currently available that directly target the fibrotic process.

Adipose tissue dysfunction drives hepatic lipid overload in metabolic dysfunction-associated steatotic liver disease (MASLD), yet the involvement of adipose tissue-derived small extracellular vesicles (sEVs) remains unclear. Herein, we showed that transplanting adipose tissue from high‑fat diet (HFD)-fed male mice exacerbated insulin resistance and hepatic steatosis in lean recipients. Adipose‑specific Sirt3 overexpression (Sirt3^AKI) alleviated insulin resistance and liver steatosis in HFD-fed male mice, whereas adipose‑specific Sirt3 knockdown aggravated these phenotypes. Moreover, adipose sEV miRNAs regulated hepatic lipid metabolism in Sirt3^AKI male mice. MicroRNA sequencing identified miR-30a-3p was increased in the circulating sEVs from HFD-fed male mice, while decreased in sEVs from Sirt3OE adipocytes and Sirt3^AKI male mice. Mechanistically, miR‑30a‑3p promoted hepatic steatosis by targeting Becn1; this process was suppressed when Sirt3 downregulated miR‑30a‑3p transcription via deacetylation of H3K56. These findings highlight the critical role of adipose sEV microRNAs in driving hepatocyte lipotoxicity, and suggest miR-30a-3p inhibition as a promising MASLD therapy.

The transition from acute kidney injury (AKI) to chronic kidney disease (CKD) represents a distinct clinical syndrome critically driven by mitochondrial dy

This study uses Scientometric analysis to review Sigesbeckiae Herba (SH) research worldwide from 1980 to 2024. Data-driven analysis identifies patterns, partnerships, and possibilities. Due to its wide profile and traditional medical uses, SH is gaining attention, according to this research. China has made the most important contributions to SH research, followed by the United stated of America and Korea. Countries and organizations have not collaborated on SH research. We found “anti-inflammation,” “rheumatic arthritis,” and “NF-κβ” using keyword co-occurrence analysis. Citation analysis showed SH research's most prominent institutions, journals, and authors, offering a complete snapshot of organization and diffusion. The data shows that this subject has received substantial academic interest despite a reduction in publications since 2019. These findings highlight the need for cooperation, multidisciplinary methods, and attention to underrepresented disciplines for academics, funding organizations, and policymakers. SH has been used to cure inflammation. Sigesbeckia orientalis L., S. pubescens Makino, and S. glabrescens Makino are the primary botanical sources. This research extensively evaluates SH literature, focusing on its botanical properties, bioactive components, pharmacological effects, and probable toxicity. More than three hundred phytochemicals, including flavonoids, diterpenoids, sesquiterpenoids, oxylipins, and lignoids, were identified in the extract, many of which are known to exert diverse biological effects. The extracts of SH are used in traditional Chinese medicine (TCM) due to its immunomodulatory, anti-inflammatory, and anti-cancer activities and are being considered for cosmetics and skin issues. Pharmacological benefits of diterpenoids, sesquiterpenoids, and flavonoids are found. The study recommends further research and cooperation to enhance TCM and herbal research by comparing the chemical and pharmacological properties of these three SH species.

Background: Sigesbeckia glabrescens Makino (SG) has been traditionally used for rheumatism and joint protection. However, the anti-arthritic effects and underling mechanisms of SG have not been demonstrated. In this study, we investigated the anti-arthritic effects and mechanisms of SG extract (SGE) on collagen-induced arthritic rats and interleukin (IL)-1β-stimulated human synovial SW982 cells. Methods: Rats were induced to arthritis by collagen for 15 days and then received SGE treatment for 35 days. The body weight and arthritis severity score of the rats were monitored weekly. At the end of the experiment, the radiographic and histological changes of rats’ hind paw were obtained; the serum C-reactive protein was detected by enzyme-linked immunosorbent assay (ELISA); the expression levels of interleukin (IL)- 1β, IL6 and IL-10 in the joint muscles were determined by ELISA and immunohistochemical staining; and the level of regulatory T cells (Tregs) in the spleen was detected using flow cytometry. In addition, 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and scratch wound healing assay were used to evaluate the proliferation of SW982 synovial cells. ELISA, western blot and immunofluorescence staining were used to investigate the anti-inflammatory mechanisms of SGE on IL-1β-induced SW982 cells and joint muscles of CIA rats. Results: SGE attenuated the collagen-induced hind paw swelling, cartilage damage and bone erosion. SGE inhibited the synovial hyperplasia to the articular cavity in the toe joint and ankle. Moreover, SGE decreased the production of C-reactive protein in serum and the expression of IL-6, IL-1β, cyclooxygenase-2 (COX-2) and phosphorylation of NF-κB p65 in the joint muscles. SGE also recovered the decreased Tregs. Results from the in vitro experiments showed that SGE not only inhibited the proliferation and migration of human synovial cell but also inhibited the IL-1β-induced expression of IL-6 and IL-8. Similarly, SGE inhibited the activation of NF-κB and the expression of COX-2. Conclusions: SGE attenuated the collagen-induced arthritis through inhibiting the synovial hyperplasia and inflammation.