Expression and significance of SOX B1 genes in glioblastoma multiforme patients.

The overall survival of glioblastoma multiforme (GBM) patients remains poor. To improve patient outcomes, effective diagnostic and prognostic biomarkers for GBM are needed. In this study, we first applied bioinformatic analyses to identify biomarkers for GBM, focusing on SOX (sex-determining region on the Y chromosome (SRY)-related high mobility group (HMG) box) B1 family members. The ONCOMINE, GEPIA, LinkedOmics and CCLE databases were used to assess mRNA expression levels of the SOX B1 family members in different cancers and normal tissue. Further bioinformatic analysis was performed using the ONCOMINE database in combination with the LinkedOmics data set to identify the prognostic value of SOX B1 family members for GBM. We found mRNA expression levels of all tested SOX B1 genes were significantly increased in GBM. In the LinkedOmics database, increased expression of SOX3 indicated a better overall survival. In GEPIA databases, increased expression of all SOX B1 family members suggested an improved overall survival, but none of them were statistically different. Then, Transwell assays and wound healing were employed to evaluate the motility and invasive captivity of U251 cells when silencing SOX2 and SOX3. We found exogenous inhibition of SOX2 appeared to reduce the migration and invasion of U251 cells in vitro. Collectively, our research suggested that SOX2 might serve as a cancer-promoting gene to identify high-risk GBM patients, and SOX3 had the potential to be a prognostic biomarker for GBM patients.

Sestrin2 as a gatekeeper of cellular homeostasis: Physiological effects for the regulation of hypoxia-related diseases.

Sestrin2 (SESN2) is a conserved stress-inducible protein (also known as hypoxia-inducible gene 95 (HI95)) that is induced under hypoxic conditions. SESN2 represses the production of reactive oxygen species (ROS) and provides cytoprotection against various noxious stimuli, including hypoxia, oxidative stress, endoplasmic reticulum (ER) stress and DNA damage. In recent years, the determination of the regulation and signalling mechanisms of SESN2 has increased our understanding of its role in the hypoxic response. SESN2 has well-documented roles in hypoxia-related diseases, making it a potential target for diagnosis and treatment. This review discusses the regulatory mechanisms of SESN2 and highlights the significance of SESN2 as a biomarker and therapeutic target in hypoxia-related diseases, such as cancer, respiratory-related diseases, cardiovascular diseases and cerebrovascular diseases.

Corrigendum: Sestrin2 protects against hypoxic nerve injury by regulating mitophagy through SESN2/AMPK pathway.

[This corrects the article DOI: 10.3389/fmolb.2023.1266243.].

Citrus tangerine pith extract alleviates hypoxia-induced ileum damage in mice by modulating intestinal microbiota.

Visitors to high altitude are susceptible to hypoxia-induced acute intestinal mucosal barrier injury and severe gastrointestinal disorders, which are life-threatening. Citrus tangerine pith extract (CTPE) is rich in pectin and flavonoids and has been proved to enhance intestinal health and improve gut dysbiosis. In this study, we aim to explore the protective effect of CTPE on ileum injury induced by intermittent hypobaric hypoxia in a mouse model. Balb/c mice were divided into blank normoxia (BN), blank hypobaric hypoxia (BH), hypobaric hypoxia plus CTPE (TH), and hypobaric hypoxia plus Rhodiola extract (RH) groups. From the 6th day of gavage, mice in BH, TH, and RH groups were transferred into a hypobaric chamber at a simulated elevation of 6000 m for 8 hours per day for 10 days. Then half the mice were tested for small intestine movement, and others were used to evaluate intestinal physical barrier function, inflammation, and gut microbiota. Results showed that CTPE reversed the increase of intestinal peristalsis, effectively attenuated impaired structural integrity of ileum, improved the mRNA and protein expression levels of tight junction proteins, and reduced serum D-LA content in mice to alleviate hypoxia-induced mucosal barrier damage. Moreover, CTPE supplementation ameliorated hypoxia-induced intestinal inflammation response by significantly downregulating the proinflammatory cytokines IL-6, TNF-α and IFN-γ. By 16S rDNA gene sequencing of gut microbiota, CTPE significantly increased the abundance of probiotic Lactobacillus, suggesting that CTPE may be used as a prebiotic to regulate ecology of intestinal microorganisms. In addition, Spearman rank correlation analysis revealed that changed gut microbiota were significantly correlated with alteration of intestinal barrier function indexes. Taken together, these results indicate that CTPE effectively alleviates hypoxia-induced intestinal injury in mice and enhances intestinal integrity and barrier function by altering intestinal microbiota composition.

Sestrin2 protects against hypoxic nerve injury by regulating mitophagy through SESN2/AMPK pathway.

Hypoxia induced by high altitude can lead to severe neurological dysfunction. Mitophagy is known to play a crucial role in hypoxic nerve injury. However, the regulatory mechanism of mitophagy during this injury remains unclear. Recent studies have highlighted the role of Sestrin2 (SESN2), an evolutionarily conserved stress-inducible protein against acute hypoxia. Our study demonstrated that hypoxia treatment increased SESN2 expression and activated mitophagy in PC12 cells. Furthermore, the knock-out of Sesn2 gene led to a significant increase in mitochondrial membrane potential and ATP concentrations, which protected the PC12 cells from hypoxic injury. Although the AMPK/mTOR pathway was significantly altered under hypoxia, it does not seem to participate in mitophagy regulation. Instead, our data suggest that the mitophagy receptor FUNDC1 plays a vital role in hypoxia-induced mitophagy. Moreover, SESN2 may function through synergistic regulation with other pathways, such as SESN2/AMPK, to mediate cellular adaptation to hypoxia, including the regulation of mitophagy in neuron cells. Therefore, SESN2 plays a critical role in regulating neural cell response to hypoxia. These findings offer valuable insights into the underlying molecular mechanisms governing the regulation of mitophagy under hypoxia and further highlight the potential of SESN2 as a promising therapeutic target for hypoxic nerve injury.

Role of mitochondrial reactive oxygen species in homeostasis regulation.

Mitochondria are the main source of reactive oxygen species (ROS) in cells. Early studies have shown that mitochondrial reactive oxygen species (mROS) are related to the occurrence and adverse outcomes of many diseases, and are thus regarded as an important risk factor that threaten human health. Recently, increasing evidence has shown that mROS are very important for an organism's homeostasis. mROS can regulate a variety of signaling pathways and activate the adaptation and protection behaviors of an organism under stress. In addition, mROS also regulate important physiological processes, such as cell proliferation, differentiation, aging, and apoptosis. Herein, we review the mechanisms of production, transformation, and clearance of mROS and their biological roles in different physiological processes.

[Effects of three Polyphenolic compounds on the intestinal flora of mice exposed simulated intermittent plateau hypoxia].

OBJECTIVE: To investigate the protective effects of three Polyphenolic compounds on intestinal microbial communities in mice exposed intermittent plateau hypoxia. METHODS: In this study, 60 healthy male Balb/c mice were randomly divided into plain control group, plateau control group, primary anthocyanin intervention group, quercetin intervention group and resveratrol intervention group, 12 mice in each group. Primary anthocyanin, quercetin and resveratrol were administrated by gavage at the doses of 50, 100 and 20 mg/kg in pharmacological intervention group, respectively. After exposure of the mice to simulation plateau-condition for 30 days, the serum samples were collected for DAO testing, sterile feces were collected in mice, and the diversity and genus level of the mouse gut bacteria were detected by using 16S rRNA technology. Ileum tissue was fixed and stained with HE. RESULTS: HE staining showed that the plateau control group had significant damage to the intestinal tissue structure compared to the plain control group, and the serum DAO concentration was increased (P＜0.05), but there was no statistical difference in the abundance and diversity of intestinal flora species. Contrast to simulated intermittent plateau hypoxia group, the structure of the intestine tissue and the level of DAO in the quercetin intervention group and resveratrol intervention group were improved(P＜0.05), the abundance and α diversity of the intestinal flora were decreased, the relative abundance of Bacteroidetes was reduced(P＜0.05), and the Firmicutes was increased. Concomitantly, significant decreases in relative abundance were observed for Corynebacterium glutamicum and Lactobacillus reuteri(P＜ 0.05). CONCLUSION: Quercetin and resveratrol showed some degree of protection to mice intestinal microbial communities, and increased the diversity and the abundance of the dominant flora and inhibited the growth of conditional pathogenic bacteria.