Anti-inflammatory and antioxidant traditional Chinese Medicine in treatment and prevention of osteoporosis.

A metabolic bone disorder called osteoporosis is characterized by decreased bone mass and compromised microarchitecture. This condition can deteriorate bones and raise the risk of fractures. The two main causes of osteoporosis are an increase in osteoclast activity or quantity and a decrease in osteoblast viability. Numerous mechanisms, including estrogen shortage, aging, chemical agents, and decreased mechanical loads, have been linked to osteoporosis. Inflammation and oxidative stress have recently been linked to osteoporosis, according to an increasing number of studies. The two primary medications used to treat osteoporosis at the moment are bisphosphonates and selective estrogen receptor modulators (SERMs). These medications work well for osteoporosis brought on by aging and estrogen deprivation, however, they do not target inflammation and oxidative stress-induced osteoporosis. In addition, these drugs have some limitations that are attributed to various side effects that have not been overcome. Traditional Chinese medicine (TCM) has been applied in osteoporosis for many years and has a high safety profile. Therefore, in this review, literature related to botanical drugs that have an effect on inflammation and oxidative stress-induced osteoporosis was searched for. Moreover, the pharmacologically active ingredients of these herbs and the pathways were discussed and may contribute to the discovery of more safe and effective drugs for the treatment of osteoporosis.

Cuproptosis-a potential target for the treatment of osteoporosis.

Osteoporosis is an age-related disease of bone metabolism marked by reduced bone mineral density and impaired bone strength. The disease causes the bones to weaken and break more easily. Osteoclasts participate in bone resorption more than osteoblasts participate in bone formation, disrupting bone homeostasis and leading to osteoporosis. Currently, drug therapy for osteoporosis includes calcium supplements, vitamin D, parathyroid hormone, estrogen, calcitonin, bisphosphates, and other medications. These medications are effective in treating osteoporosis but have side effects. Copper is a necessary trace element in the human body, and studies have shown that it links to the development of osteoporosis. Cuproptosis is a recently proposed new type of cell death. Copper-induced cell death regulates by lipoylated components mediated via mitochondrial ferredoxin 1; that is, copper binds directly to the lipoylated components of the tricarboxylic acid cycle, resulting in lipoylated protein accumulation and subsequent loss of iron-sulfur cluster proteins, leading to proteotoxic stress and eventually cell death. Therapeutic options for tumor disorders include targeting the intracellular toxicity of copper and cuproptosis. The hypoxic environment in bone and the metabolic pathway of glycolysis to provide energy in cells can inhibit cuproptosis, which may promote the survival and proliferation of various cells, including osteoblasts, osteoclasts, effector T cells, and macrophages, thereby mediating the osteoporosis process. As a result, our group tried to explain the relationship between the role of cuproptosis and its essential regulatory genes, as well as the pathological mechanism of osteoporosis and its effects on various cells. This study intends to investigate a new treatment approach for the clinical treatment of osteoporosis that is beneficial to the treatment of osteoporosis.

Identification and validation of a ferroptosis-related gene signature for predicting survival in skin cutaneous melanoma.

PURPOSE: Ferroptosis plays a crucial role in the initiation and progression of melanoma. This study developed a robust signature with ferroptosis-related genes (FRGs) and assessed the ability of this signature to predict OS in patients with skin cutaneous melanoma (SKCM). METHODS: RNA-sequencing data and clinical information of melanoma patients were extracted from TCGA, GEO, and GTEx. Univariate, multivariate, and LASSO regression analyses were conducted to identify the gene signature. A 10 FRG signature was an independent and strong predictor of survival. The predictive performance was assessed using ROC curve. The functions of this gene signature were assessed by GO and KEGG analysis. The statuses of low-risk and high-risk groups according to the gene signature were compared by GSEA. In addition, we investigated the possible relationship of FRGs with immunotherapy efficacy. RESULTS: A prognostic signature with 10 FRGs (CYBB, IFNG, FBXW7, ARNTL, PROM2, GPX2, JDP2, SLC7A5, TUBE1, and HAMP) was identified by Cox regression analysis. This signature had a higher prediction efficiency than clinicopathological features (AUC = 0.70). The enrichment analyses of DEGs indicated that ferroptosis-related immune pathways were largely enriched. Furthermore, GSEA showed that ferroptosis was associated with immunosuppression in the high-risk group. Finally, immune checkpoints such as PDCD-1 (PD-1), CTLA4, CD274 (PD-L1), and LAG3 were also differential expression in two risk groups. CONCLUSIONS: The 10 FRGs signature were a strong predictor of OS in SKCM and could be used to predict therapeutic targets for melanoma.