Motile sperm head morphometry in relation to sperm kinematics and freezability in cats.

Pulpitis represents a prevalent clinical condition in dentistry. Macrophages play pivotal roles in pulpitis immunopathology, while dental pulp stem cells (DPSCs) serve as key effectors in pulp tissue repair and immune regulation. Although mesenchymal stem cells are known to regulate immunity through mitochondrial transfer, this mechanism remains unexplored in pulpitis. This study investigated how mitochondrial transfer influences pulpitis progression and resolution. To investigate DPSC-macrophage mitochondrial transfer and its role in polarisation of macrophages, Lipopolysaccharide-stimulated cocultures were established. Transfer dynamics were analysed by fluorescence microscopy and flow cytometry. Macrophage polarisation (assessed via quantitative real-time polymerase chain reaction (qRT-PCR)/flow cytometry) in the cocultures was detected after mitochondrial transfer agonist/inhibitor treatment. Macrophage polarisation (assessed via qRT-PCR/flow cytometry) and mitochondrial function (reactive oxygen species production, membrane potential) were compared between mitochondria-receiving (Mito+) and non-receiving (Mito-) macrophages. Immunometabolic profiles (itaconate/succinate) were evaluated by qRT-PCR/immunofluorescence. Human dental pulp explants and experimental rat pulpitis models demonstrated the anti-inflammatory and reparative effects of mitochondrial transfer agonists. Data were analysed by one-way ANOVA and unpaired t-tests (α = 0.05). Mitochondrial transfer from DPSCs to macrophages reduced during inflammation. Pharmacological inhibition of mitochondrial transfer exacerbated M1 macrophage polarisation, whereas its enhancement promoted M2 polarisation. Mito+ macrophages exhibited stronger M2 polarisation, improved mitochondrial function, and reduced itaconate/succinate metabolism compared to Mito- cells. Notably, using the inflamed dental pulp explant and the experimental rat pulpitis model, we demonstrated that augmenting mitochondrial transfer can effectively alleviate pulpitis and promote repair. Mitochondrial transfer from dental pulp stem cells to macrophages via tunnelling nanotubes improved macrophage metabolic profiles. Enhanced mitochondrial transfer promoted M2 macrophage polarisation, thereby alleviating pulpal inflammation and promoting repair.

The identification of autoantibodies against nephrin, a key signaling protein of the podocyte slit diaphragm, and their pathogenic role in patients with minimal change disease (MCD) has substantially changed our understanding of primary podocytopathies. However, details on underlying immune pathophysiological mechanisms such as the relation of anti-nephrin autoantibodies with immune cell subsets and therapy response remain to be determined. In this prospective study, we evaluated blood samples from adults with newly diagnosed, biopsy-proven MCD for circulating anti-nephrin antibodies using immunoprecipitation (IP) and B-cell subpopulations by fluorescence-activated cell sorting. Samples were collected at diagnosis (t0) and after 8 weeks of steroid therapy (t1). We detected anti-nephrin antibodies in 12 of 17 (70.6%) therapy-naïve patients with MCD at t0. All 12 patients (100%) positive for anti-nephrin antibodies achieved complete remission with no anti-nephrin antibodies detectable after 8 weeks of steroid treatment (t1). Two of 5 anti-nephrin negative patients (40%) did not reach clinical remission at t1. Anti-nephrin positive patients exhibited a larger fraction of plasmablasts than anti-nephrin negative patients at t0, albeit not statistically significant. Plasmablasts, naïve B cells, and transitional B cells significantly decreased, whereas marginal zone-like B cells increased within 8 weeks of steroid treatment in anti-nephrin positive patients (t1). Our study shows, for the first time, a therapeutically relevant short-term effect of steroids on the B-cell compartment and anti-nephrin antibody levels, explaining the high clinical response rate in patients with anti-nephrin-associated MCD.

Afzelin resists UVA damage through autophagy and synergizes with ganoderic acid A to skin photoaging.

Prolactinomas are the most common functional pituitary adenomas, and dopamine agonists (DAs) are the first-line therapy; however, approximately 10-30% of patients develop resistance, highlighting the need for effective sensitization strategies. In clinical specimens, we observed reduced p300 expression in tumors with poor DA responsiveness, and p300 levels were inversely associated with DA dosage. In cellular and xenograft models, DAs decreased p300 by suppressing the cAMP/PKA/CREB pathway. We therefore tested whether upregulating or activating p300 could enhance DA efficacy and investigated the underlying mechanism using immunohistochemistry, immunofluorescence, Western blot, genetic manipulations, RNA sequencing, CUT&Tag, ChIP-qPCR, Seahorse metabolic assays, flow cytometry, co-immunoprecipitation, and GST pull-down assays. Augmenting p300 markedly potentiated DA-induced antitumor effects in vitro and in vivo, a process accompanied by the elevated histone H3K18 lactylation (H3K18la). Mechanistically, p300-dependent H3K18la promoted transcriptional upregulation of Ndufs7 and Washc1. NDUFS7 induction was associated with increased mitochondrial ROS, whereas WASH1 bound the ubiquitin-associated domain of p62, impairing recognition and clearance of damaged mitochondria, suppressing mitophagy, and thereby sustaining mitochondrial ROS accumulation and apoptosis. Moreover, YF-2, a p300 HAT-domain activator, synergized with DAs to inhibit tumor growth in MMQ and AtT-20 cells. Together, these data identify a p300-H3K18la-NDUFS7/WASH1 axis that links mitophagy inhibition to mitochondrial ROS accumulation and provide a mechanistic rationale for targeting p300 as an adjuvant approach to improve DAs efficacy in prolactinomas.

Breast cancer is a global health challenge for women and chemoresistance is a major contributor to its high mortality rates. Quercetin (Que), a flavonoid with antioxidant, antiviral, anti‑tumor and anti‑inflammatory properties, sensitizes cancer cells to chemotherapy. The present study investigated the mechanism by which Que regulates ATP‑binding cassette (ABC) transporter expression in MCF‑7 cells using a PTEN overexpression plasmid and the PI3K inhibitor LY294002. The present study assessed cell viability via Cell Counting Kit‑8 and Hoechst 33342 staining and analyzed mRNA and protein expression levels by reverse transcription‑quantitative PCR and western blotting. Apoptosis was evaluated by flow cytometry and ABCG2 expression was detected by immunofluorescence. Furthermore, the present study determined the effect of Que on drug uptake using a Rhodamine 123 accumulation assay. The results of the present study demonstrated that Que suppresses cell viability and induces apoptosis in MCF‑7 cells. Moreover, it enhances intracellular drug accumulation and downregulates ABC transporter expression by modulating the PTEN/PI3K/AKT signaling pathway.

Multimodal anticancer potential of newly synthesized palladium(II), platinum(II), and gold(III) complexes with 2-(Thiazol-2-yl)pyridine-4,5-dicarboxylate dimethyl ester.

KPT-8602 combined with IFN-γ released ZBP1-PANoptosome to inhibit the progression of primary central nervous system lymphoma.

Quercetagitrin targets EIF3D to activate NCOA4-mediated ferritinophagy-dependent ferroptosis for the treatment of non-small cell lung cancer.

Context-specific roles of DDX60 in colorectal cancer via autophagy regulation and DDX58 signaling.

Double-negative T cells (DNTs) are significantly elevated in autoimmune diseases and are thought to play an important role in inflammation. The purpose of this study was to explore their role in childhood-onset systemic lupus erythematosus (cSLE). DNTs, as well as T and B cell subsets in peripheral blood, were detected by flow cytometry in 78 patients, including 34 cSLE. Clinical and laboratory data of cSLE patients were collected to analyze the correlation between DNTs and these indices, including demographics: proportion of female patients and mean age (± SD); Organ involvement: presence of lupus nephritis, neuropsychiatric manifestations, and pulmonary involvement; Hematologic parameters: leukopenia, anemia, and thrombocytopenia (WBC, Hb, and PLT counts); Autoantibody profiles: ANA, anti-dsDNA, and anti-Sm antibodies. The changes in DNT levels after glucocorticoid treatment were observed, and the effects of different doses of glucocorticoids on DNTs were analyzed. DNT levels were significantly increased in the peripheral blood of cSLE patients. DNTs were correlated with SLE disease activity, organ involvement, the production of autoantibodies, naive B cells, and plasmablasts. DNT levels increased after low-dose glucocorticoid treatment (9.12 ± 1.43 vs 14.24 ± 1.36, p < 0.01) but gradually decreased with increasing glucocorticoid doses (14.24 ± 1.36 vs 13.45 ± 1.51 vs 7.45 ± 1.01 vs 4.72 ± 1.20, p < 0.05). DNT levels significantly decreased from the fourth day of glucocorticoid pulse therapy. DNT levels were positively correlated with disease activity in cSLE patients, and the effect of glucocorticoid dose on DNT levels varied. Key Points • DNT cells are significantly elevated in cSLE patients and correlate with disease activity, organ involvement, and autoantibody profiles. Low-dose glucocorticoids transiently increase circulating DNT levels, while higher doses progressively reduce DNT frequencies. DNT levels positively correlate with B-cell subsets, suggesting a potential role in autoantibody production in pediatric SLE. • Dynamic changes in DNTs may be influenced by glucocorticoid treatment.

Immunological effects of coinfections with Toxoplasma gondii, Helicobacter pylori, and Epstein-Barr virus on anisakiasis associated phenotypes.

Cyasterone regulates lipid metabolism and autophagy mediated by the AMPK signaling pathway to improve KOA synovitis.

Xbp1-driven lipid metabolism promotes immunosuppression in lung cancer: Jianpi Chutan Jiedu formula reshapes metabolic-immune crosstalk.

PBX1-mediated transcription of AP1M2 promotes triple-negative breast cancer malignant progression and docetaxel resistance.

Bipolar CD4-targeted dual-DARPin-55/57 lipid nanoparticle enables efficient CRISPR/Cas-mediated HIV-1 DNA excision and reactivation blockade in latent CD4 T cell lines.

Cold storage, warm outcomes: Viability of Haematopoietic stem cells after extended cryopreservation.

ADAM8 negatively regulates the osteogenic differentiation of rat tendon stem cells through inhibiting the PI3K/AKT signaling pathway.

Berberine reverses impaired adipose angiogenesis to promote beige adipogenesis by HIF-1α/PRDM16 signaling.

IMM-H004 attenuates neutrophil pyroptosis following ischemic stroke via a CKLF1 dependent mechanism.