Formulation and administration timing of lipid derivatized JAK-inhibitor and corticosteroid modulate saRNA-LNP inflammation and expression.

Zhi-Gan Formula improved insomnia and anxiety comorbidity in a mouse model via PACAP signaling in the medial prefrontal cortex.

Chaihu Shugan San exerts antidepressant effects by driving microglial M2 polarization via inhibition of the IL-1β/JNK signaling pathway.

Sishen Wan suppresses colon cancer through dual inhibition of PI3K/AKT/mTOR and STAT3-mitophagy pathways: Network pharmacology and experimental validation.

Danhong injection alleviates sepsis-induced acute lung injury by regulating AGE/RAGE/AKT pathway.

Identification and functional analysis of biallelic loss-of-function variants of WNT7B in a Chinese family affected with PDAC syndrome.

Differential methylation of the miR-132/212 promoter contributes to PRRSV resistance by targeting FOXA1 and MYD88 in pigs.

Huang Qi Decoction inhibits differentiation of hepatic oval cells to cholangiocytes via the β-catenin pathway to ameliorate hepatic fibrosis.

Targeting translocator protein (TSPO) ameliorates inflammation and maintains mitochondrial homeostasis to protect against dry eye.

Deficiency in beclin1 alleviates doxorubicin-induced liver injury through inhibiting ferroptosis and autophagy.

TLR9-mediated activation of the NLRP3 inflammasome in Fusarium solani-induced keratitis.

Dentin bonding agents and camphorquinone-induced cytotoxicity, 8-isoprostane and prostaglandin production is associated with CYP450, NQO1, NQO2, GST, and GSH peroxidase in human dental pulp cells.

The purpose of this study was to evaluate how the immune response to recombinant antigens is impacted by formulation with a panel of Montanide adjuvants Montanide IMS 1313 VG NST (M1313), Montanide ISA 660 VG (M660) and Montanide Gel 02 (MGel02) administered intradermally (ID) to pigs in combination with four antigens - FliC, ClpP, GroEL and YopN (Ag), which were previously found to be immunogenic when administered to pigs via the intramuscular route. M660, MGel02 and M1313 plus Ag formulations induced significantly elevated serum anti-ClpP IgG, anti-GroEL or anti-FliC IgG titres relative to pigs administered their respective adjuvants alone. Further, M660, MGel02, and M1313 plus Ag formulations contributed to significantly elevated anti-ClpP IgG, and anti-FliC IgG titres in serum, over time. No significant mucosal IgA titers were detected. Pigs administered the ID subunit vaccine formulated with M660 showed significantly elevated antigen-specific IFNγ secretion, a marker of a strong cell-mediated immune response, but these animals also developed lesions at the site of injection accompanied by evidence of significant suppurative inflammation. In a second study, histological analysis after 7 days or 24 h showed significantly increased granuloma formation, cellular recruitment, suppurative inflammation and necrosis, with reduced evidence of these pathologies in response to M660 alone. The tissue site reactions showed significantly elevated IL-1β, but not IL-6 or IFNγ, protein expression. Further, results showed significantly elevated CXCL2 gene expression between 24 h and 7 days, but not differential expression of NLRP3 or MSR1 genes, despite these genes being known to contribute to elevated IL-1β secretion and the associated pathology. The elevated expression of CXCL2 expression observed in the M660 + Ag group shows agreement with the neutrophil infiltration observed in the histopathology, which is consistent with neutrophil recruitment and involvement. These studies indicate that M660 + Ag contribute to humoral and cell-mediated immunity, but reduced doses should be assessed to ensure immunity without site reactions.

HAX1 overexpression induces osteogenic differentiation of periodontal ligament stem cells via the MEK/ERK signaling cascade.

Dietary L-Se-methylselenocysteine suppresses liver tumor progression via integrated antioxidant, immune, and apoptotic modulation in mice.

The cinnamaldehyde-thiosemicarbazone-zinc (II) complex induces apoptosis in CAL-27 cells.

Triple-negative breast cancer (TNBC) is a highly aggressive subtype of breast cancer lacking estrogen receptor (ER), progesterone receptor (PR), and HER2 expression. Among its heterogeneous subtypes, luminal androgen receptor-positive (LAR) TNBC is driven by androgen signaling and presents limited treatment options. We previously identified dehydrogenase/reductase SDR family member 11 (DHRS11) as a novel enzyme involved in androgen biosynthesis, and demonstrated that Kobochromone A (KC-A), a polyphenol isolated from Carex kobomugi, inhibited androgen-driven proliferation in LAR TNBC cells via DHRS11 inhibition and AR downregulation. In this study, we synthesized 23 structural derivatives of KC-A and identified WH23 as the most potent DHRS11 inhibitor (IC50 = 37 nM). Molecular docking and MM-PBSA analysis revealed that the 2'-hydroxy group of WH23 forms a hydrogen bond with His210 of DHRS11, which was validated by site-directed mutagenesis. WH23 suppressed AR mRNA and protein expression, reduced 11-ketodihydrotestosterone (11KDHT)-induced c-Myc expression, and inhibited proliferation of MDA-MB-453 cells. Additionally, WH23 inhibited PI3K/AKT signaling, reducing phosphorylation of PDK1, AKT, mTOR, and ERK. Capivasertib (Cap), a clinically approved pan-AKT inhibitor, induced DHRS11 expression in MDA-MB-453 cells. Although Cap and WH23 did not show synergistic cytotoxicity in parental cells, Cap-resistant (Cap-R) cells, which exhibited elevated DHRS11 and c-Myc expression, showed significant sensitivity to the combination. In Cap-R cells, the combination of Cap and WH23 significantly induced apoptosis, demonstrating a synergistic anticancer effect. These findings establish WH23 as a dual-acting compound targeting both androgen biosynthesis and AR signaling, with potential to overcome AKT inhibitor resistance in LAR TNBC.

Mesaconine alleviates hyperalgesia in CFA-induced mice by modulating YAP1 to suppress cell ferroptosis within the spinal cord.

Radiofrequency therapy attenuates hypertrophic scar formation in rabbit ears by modulating the TGF-β1/Smad3 signaling pathway.

N-acetyl-cysteine alleviates nandrolone decanoate-induced hippocampal cell apoptosis in rats via reversing protein expressions of S1P1, Akt and FOXO3a signaling pathway.