Protective effect of vitamin B6 against doxorubicin-induced cardiotoxicity by modulating NHE1 expression.

Doxorubicin (DOX) has been used to treat various types of cancer, but its application is limited due to its heart toxicity as well as other drawbacks. Chronic inhibition of Na+ /H+ exchanger (NHE1) reduces heart failure and reduces the production of reactive oxygen species (ROS); vitamin B6 (VitB6 ) has been demonstrated to have a crucial role in antioxidant mechanism. So, this study was designed to explore the effect of VitB6 supplement on the DOX-induced cardiotoxicity and to imply whether NHE1 is involved. Ultrasonic cardiogram analysis revealed that VitB6 supplement could alleviate DOX-induced cardiotoxicity; hematoxylin and eosin (HE) and Masson's staining further confirmed this effect. Furthermore, VitB6 supplement exhibited significant antioxidative stress and antiapoptosis effect, which was evidenced by decreased serum malondialdehyde (MDA) content and increased serum superoxide dismutase (SOD) content, and decreased Bcl-2-associated X protein/B-cell lymphoma-2 ratio, respectively. Collectively, VitB6 supplement may exert antioxidative and antiapoptosis effects to improve cardiac function by decreasing NHE1 expression and improve DOX-induced cardiotoxicity.

The efficacy of endoscopic dacryocystorhinostomy in the treatment of dacryocystitis: A systematic review and meta-analysis.

BACKGROUND: This article aimed to discuss the efficacy and safety of endoscopic dacryocystorhinostomy (EDCR) versus external dacryocystorhinostomy (EX-DCR) for the treatment of dacryocystitis by meta-analysis. METHODS: All randomized controlled trials that met the inclusion and exclusion criteria were collected by searching the following databases: PubMed, Web of Science, China National Knowledge Infrastructure, and Wanfang, from the establishment of the database to June 2023. Meta-analysis was performed using Stata 17.0 software and review manager 5.4 software. In the collected trials, the observation group was treated with EDCR, whereas the control group was treated with EX-DCR. RESULTS: A total of 10 studies involving 969 patients were included in this analysis. There was a similar surgical success rate in the treatment of dacryocystitis between the 2 groups (RR = 1.021, 95% CI [0. 803, 1.297], P = 0. 865). However, compared with the control group, patients in the observation group had a higher total effective rate of treatment (RR = 1. 195, 95% CI [1. 063, 1.343], P = .003), and shorter operative time (WMD = -23.640, 95% CI [-35.533, -11.747], P < .001), and less intraoperative blood loss (WMD = -50.797, 95% CI [-80.339, -21.255], P = .001), shorter length of hospital stays (WMD = -4.570, 95% CI [-5.992, -3.148], P < .001), and lower incidence of adverse events (RR = 0.295, 95% CI [0.173, 0.504], P < .001). CONCLUSION: EDCR is an effective and safe surgical procedure for the treatment of dacryocystitis and can be used as an alternative to EX-DCR.

The chromatin remodeling factor Arid1a cooperates with Jun/Fos to promote osteoclastogenesis by epigenetically upregulating Siglec15 expression.

Osteoporosis is characterized by an imbalance between osteoclast-mediated bone resorption and osteoblast-related bone formation, particularly increased osteoclastogenesis. However, the mechanisms by which epigenetic factors regulate osteoclast precursor differentiation during osteoclastogenesis remain poorly understood. Here, we show that the specific knockout of the chromatin remodeling factor Arid1a in bone marrow-derived macrophages (BMDMs) results in increased bone mass. The loss of Arid1a in BMDM inhibits cell-cell fusion and maturation of osteoclast precursors, thereby suppressing osteoclast differentiation. Mechanistically, Arid1a increases the chromatin access in the gene promoter region of sialic acid-binding Ig-like lectin 15 (Siglec15) by transcription factor Jun/Fos, which results in the upregulation of Siglec15 and promotion of osteoclast differentiation. However, the loss of Arid1a reprograms the chromatin structure to restrict Siglec15 expression in osteoclast precursors, thereby inhibiting BMDM differentiation into mature osteoclasts. Deleting Arid1a after ovariectomy (a model for postmenopausal bone loss) alleviated bone loss and maintained bone mass. In summary, epigenetic reprogramming mediated by Arid1a loss suppresses osteoclast differentiation and may serve as a promising therapeutic strategy for treating bone loss diseases.

Osteoporosis is a common disease, usually diagnosed by decreased bone density and increased fragility. The people with osteoporosis has higher risk of fractures. Nearly one-third of the aged people will suffer from osteoporosis-related fractures and even lose their lives because of this. Therefore, there is an urgent need for early intervention and effective treatment options for osteoporosis in the aging population. Bone tissue is a highly dynamic tissue that undergoes continuous remodeling throughout an individual's entire life. The balance of remodeling depends on the bone formation mediated by osteoblasts and bone resorption by osteoclasts. When this balance is disrupted, osteoporosis occurs. Thus, the aim of our research is to explore the behind mechanism of this imbalance. Here, we demonstrate that the loss of Arid1a, a chromatin remodeler, leads to chromatin reprogramming that restricts access to promoters by transcription factors such as Jun/Fos, thereby suppressing osteoclast activation and bone resorption. Our findings offer insights into the epigenetic mechanisms underlying osteoporosis and suggest potential strategies for its prevention and treatment.