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Periodontitis, characterized by inflammation and loss of periodontal tissue, is a significant health complication for individuals with diabetes mellitus (DM). Buildup of advanced glycation end-products (AGEs) in DM poses an increased risk of periodontitis via inflammaging. Ganoderma immunomodulatory protein (GMI) shows promise in suppressing inflammaging by mitigating oxidative stress and inflammation via Nrf2 modulation. However, its specific protective effects are not fully understood. Thus, this study aimed to investigate GMI's anti-inflammaging properties and its underlying mechanism in diabetic-associated periodontitis (DP). We first simulated DP by culturing human gingival fibroblasts (HGFs) with AGEs and lipopolysaccharides from P. gingivalis (LPS). We then evaluated the impact of GMI on cell proliferation, migration and wound healing. Additionally, we assessed GMI's effects on the components of inflammaging such as reactive oxygen species (ROS) formation, cellular senescence expression, IL-6 and IL-8 secretions, and NF-κB phosphorylation. Next, we explored whether GMI's anti-inflammaging effects are mediated through the Nrf2 pathway by evaluating Nrf2 and HO-1, followed by the assessment of IL-6 and IL-8 post-Nrf2 knockdown. Our findings revealed that GMI treatment suppressed ROS production, cell senescence, IL-6 and IL-8 and NF-κB phosphorylation. Furthermore, GMI upregulated Nrf2/HO-1 expression and its protective effects were reversed when Nrf2 was knocked down. In conclusion, GMI exerts its anti-inflammaging effect via the modulation of the Nrf2/NF-κB signaling axis in DP in vitro, highlighting its potential as an effective adjunct treatment for diabetes-related periodontitis. [ABSTRACT FROM AUTHOR]

The CDEX Collaboration has been established for direct detection of lightdark matter particles, using ultra-low energy threshold p-type point-contactgermanium detectors, in China JinPing underground Laboratory (CJPL). The first1 kg point-contact germanium detector with a sub-keV energy threshold has beentested in a passive shielding system located in CJPL. The outputs from both thepoint-contact p+ electrode and the outside n+ electrode make it possible toscan the lower energy range of less than 1 keV and at the same time to detectthe higher energy range up to 3 MeV. The outputs from both p+ and n+ electrodemay also provide a more powerful method for signal discrimination for darkmatter experiment. Some key parameters, including energy resolution, dead time,decay times of internal X-rays, and system stability, have been tested andmeasured. The results show that the 1 kg point-contact germanium detector,together with its shielding system and electronics, can run smoothly with goodperformances. This detector system will be deployed for dark matter searchexperiments.

Oral submucous fibrosis (OSF) is a premalignant disorder that is associated with betel nut chewing. The purpose of the study was to establish the role of histone deacetylase (HDAC) 8, one of histone deacetylases, in the regulation of fibrotic conditions to provide a therapeutic potential for OSF. First, we examined the expression of HDAC8 in fibrotic buccal mucosal fibroblasts (fBMFs) and OSF tissues. Markers of myofibroblasts and TGF-β signaling were conducted in fBMFs with HDAC8 knockdown were examined. Furthermore, epithelial–mesenchymal transition (EMT) markers, collagen gel contraction and migration ability were also examined in fBMFs transfected with sh-HDAC8. HDAC8 inhibitor was used to analyze the collagen gel contraction and wound healing ability in fBMFs. We observed the mRNA expression of HDAC8 was significantly increased in fBMFs. Compared to normal tissues, the protein level of HDAC8 was upregulated in OSF. Next, mRNA and protein expression of HDAC8 was significantly decreased, accompanying downregulation of α-SMA and COL1A1 in fBMFs infected with sh-HDAC8. To determine the critical role of HDAC8 in OSF fibrogenesis, results revealed that TGF-β secretion and the expression of EMT transcription factor SNAIL and p-Smad were significantly decreased in HDAC8-knockdown fBMFs. We further demonstrated that collagen gel contraction and migration ability were significantly decreased in fBMFs transfected with sh-HDAC8. Last, results revealed that significantly reduced collagen gel contraction and wound healing ability in fBMFs with HDAC8 inhibitor treatment. We concluded that downregulation of HDAC8 alleviated the activities of myofibroblasts and TGF-β/Smad signaling pathway in OSF. [ABSTRACT FROM AUTHOR]