Optogenetics in taste research: A decade of enlightenment.

The electrophysiological function of the tongue involves complicated activities in taste sense, producing the perceptions of salty, sweet, bitter, and sour. However, therapies and prevention of taste loss arising from dysfunction in electrophysiological activity require further fundamental research. Optogenetics has revolutionized neuroscience and brought the study of sensory system to a higher level in taste. The year 2022 marks a decade of developments of optogenetics in taste since this technology was adopted from neuroscience and applied to the taste research. This review summarizes a decade of advances that define near-term translation with optogenetic tools, and newly-discovered mechanisms with the applications of these tools. The main limitations and opportunities for optogenetics in taste research are also discussed.

Gastrodin alleviates rat chondrocyte senescence and mitochondrial dysfunction through Sirt3.

Several researchers have focused on understanding the pathogenesis and treatment strategies for osteoarthritis (OA). Gastrodin (GAS) is a potential anti-inflammatory agent. In this study, we constructed an in vitro OA chondrocyte model by treating chondrocytes with IL-1ß. Next, we determined the expression of aging-related markers and mitochondrial functions in chondrocytes treated with GAS. Further, we constructed a "drug-component-target-pathway-disease" interactive network and determined the effect of GAS on the functions and pathways related to OA. Finally, we constructed the OA rat model by removing the medial meniscus of the right knee and transection of the anterior cruciate ligament. The results revealed that GAS reduced senescence and improved mitochondrial functions in OA chondrocytes. We used network pharmacology and bioinformatics to screen for key molecules Sirt3 and the PI3K-AKT pathway involved in regulating the effect of GAS on OA. Further studies showed an increase in SIRT3 expression and reduced chondrocyte aging, mitochondrial damage, and the phosphorylation of the PI3K-AKT pathway. The results showed that GAS ameliorates pathological changes related to aging, increases SIRT3 expression, and protects the ECM in the OA rat model. These results were consistent with our bioinformatics results and previous studies. In summary, GAS slows down the aging of chondrocytes and mitochondrial damage in OA by regulating the phosphorylation of the PI3K-AKT pathway via SIRT3.

Dissecting the effect of sphingolipid metabolism gene in progression and microenvironment of osteosarcoma to develop a prognostic signature.

Sphingolipid metabolism (SM) fuels tumorigenesis and the malignant progression of osteosarcoma (OS), which leads to an unfavorable prognosis. Elucidating the molecular mechanisms underlying SM in osteosarcoma and developing a SM-based prognostic signature could be beneficial in the clinical setting. This study included 88 frozen OS samples to recognize the vital SM-relevant genes in the development of OS utilizing univariate Cox regression. The Least Absolute Shrinkage and Selection Operator (LASSO) regression analysis was conducted on the SM- relevant genes to minimize the risk of overfitting. The prognostic signature was generate utilizing the multivariable Cox regression analysis and was verified in the validation cohort. Moreover, cellular and molecular mechanisms associated with SM have an unfavorable prognosis for OS patients and have been widely studied. Resultantly, an SM-based prognostic risk model was established according to critical prognostic genes (CBS, GLB1, and HACD1), which had an excellent ability to predict the prognosis of OS patients (AUC for the train cohort was 0.887 and AUC for validation cohort was 0.737). The high-risk OS patients identified based on this prognostic signature had significantly poor immune microenvironment, indicated by significantly low immune score (mean=216.290 ± 662.463), reduced infiltrations of 25 immune cells, including NK cells (LogFC= -0.3597), CD8+T cells ((LogFC=-0.2346), Cytolytic activity ((LogFC=-0.1998), etc. The immunosuppressive microenvironment could be due to dysregulated SM of glycolipids. Further, a nomogram was constructed by integrating the SM-based prognostic signature and clinical paraments to facilitate clinical application. The nomogram could accurately predict the prognosis of OS invalids. Collectively, this study clarified the function of SM in the development of OS and helped develop a tool for risk stratification based on SM-related genes with application in clinical settings. The results of our study will aid in identifying high-risk patients and provide individualized treatments.

Procyanidin B2 ameliorates the progression of osteoarthritis: An in vitro and in vivo study.

OBJECTIVE: Osteoarthritis (OA) is characterized by cartilage degeneration and inflammation. Procyanidin B2 (PCB2), a natural flavonoid compound, exhibits potential anti-inflammatory and anti-oxidative effects against several diseases. However, its curative effects on OA remain unclear. PURPOSE: Herein, we explored the anti-arthritic effects of PCB2 on OA onset and progress and its potential mechanism. METHODS: CCK-8 assays and EdU staining were used to assess the cytotoxic effects and cell proliferation activity of PCB2. Flow cytometry was used to detect apoptosis in chondrocytes. ELISA, qPCR, and western blotting, were applied to explore the expression of apoptosis and senescence-associated secretion phenotype (SASP) factors. The Nrf2/NF-κB signaling cascade was explored using immunofluorescence and western blotting. Additionally, we silenced the Nrf2 gene using siRNAs to verify its function in PCB2 regulation of senescence and apoptosis phenotypes. Safranin O-Fast Green (SO) and immunohistochemical staining were used to explore the effects of PCB2 on OA model rats. RESULTS: PCB2 dampened interleukin (IL)-1ß-triggered expression of SASP factors in vitro. Additionally, PCB2 diminished IL-1ß-triggered destruction of the extracellular matrix (ECM) via downregulating the expression of MMPs, while upregulating the expression of collagen II and aggrecan. In addition, PCB2 treatment reduced IL-1ß-induced apoptosis of chondrocytes. Mechanistically, PCB2 could attenuated chondrocyte senescence in vitro via the Nrf2/NF-κB pathway. Moreover, PCB2 exhibited anti-apoptotic properties via the Nrf2/BAX/Bcl-2 pathway. PCB2 alleviated knee cartilage degeneration in an OA rat model. CONCLUSIONS: Our results suggest that PCB2 may be used as a therapeutic agent for OA.