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Introduction: Neurological dysfunction induced by fluoride contamination is still one of major concern worldwide. Recently, neuroprotective roles of silent information regulator 1 (SIRT1) focusing on mitochondrial function have been highlighted. However, what roles SIRT1 exerts and the underlying regulative mechanisms, remain largely uncharacterized in such neurotoxic process of fluoride. Objectives: We aimed at evaluating the regulatory roles of SIRT1 in human neuroblastoma SH-SY5Y cells and Sprague-Dawley rats with fluoride treatment, and to further identify potential miRNA directly targeting SIRT1. Methods: Pharmacological suppression of SIRT1 by nicotinamide (NIC) and promotion of SIRT1 by adenovirus (Ad-SIRT1) or resveratrol (RSV) were employed to assess the effects of SIRT1 in mitochondrial dysfunction induced by fluoride. Also, miRNAs profiling and bioinformatic prediction were used to screen the miRNAs which can regulate SIRT1 directly. Further, chemical mimic or inhibitor of chosen miRNA was applied to validate the modulation of chosen miRNA. Results: NIC exacerbated defects in mitochondrial network dynamics and cytochrome c (Cyto C) release-driven apoptosis, contributing to fluoride-induced neuronal death. In contrast, the ameliorative effects were observed when overexpressing SIRT1 by Ad-SIRT1 in vitro or RSV in vivo. More importantly, miR-708-3p targeting SIRT1 directly was identified. And interestingly, moreover, treatment with chemically modified miR-708-3p mimic aggravated, while miR-708-3p inhibitor suppressed fluoride-caused neuronal death. Further confirmedly, overexpressing SIRT1 effectively neutralized miR-708-3p mimic-worsened fluoride neuronal death via correcting mitochondrial network dynamics. On contrary, inhibiting SIRT1 counteracted the promotive effects of miR-708-3p inhibitor against neurotoxic response by fluoride through aggravating abnormal mitochondrial network dynamics. Conclusion: These data underscore the functional importance of SIRT1 to mitochondrial network dynamics in neurotoxic process of fluoride and further screen a novel unreported neuronal function of miR-708-3p as an upstream regulator of targeting SIRT1, which has important theoretical implications for a potential therapeutic and preventative target for treatment of neurotoxic progression by fluoride. more...

T-2 toxin can induce bone and cartilage development disorder, and oxidative stress plays an important role in it. It is well known that selenomethionine (Se-Met) has antioxidative stress properties and promotes the repair of cartilage lesion, but it remains unclear whether Se-Met can relieve damaged cartilage exposure to T-2 toxin. Here, the oxidative stress and ferroptosis of chondrocytes exposure to T-2 toxin were observed. Mechanistically, T-2 toxin increased ROS, lipid ROS, MDA and Fe2+ contents in chondrocytes, decreased GSH and GPX4 activity, and inhibited the system Xc−/GSH/GPX4 antioxidant axis. In addition, the mitochondria of chondrocytes shrunk and the mitochondrial crest decreased or disappeared. However, Fer-1 (Ferrostatin-1) inhibited ferroptosis induced by T-2 toxin in chondrocytes. The Se-Met alleviated lipid peroxidation, oxidative stress, and damaged mitochondrial in T-2 toxin-infected chondrocytes, enhanced antioxidant enzyme activity, and activated the system Xc−/GSH/GPX4 axis, thereby antagonizing ferroptosis of chondrocytes and alleviating articular cartilage damage. In conclusion, our findings highlight the essentiality of ferroptosis in chondrocyte caused by T-2 toxin, elucidate how Se-Met offers protection against this injury and provide research evidence for the drug treatment target of Kashin-Beck disease. more...

Acne scars are caused by inflammatory reactions, infections, and improper handling of acne lesions. Such scars have a high incidence and are difficult to treat. There are many methods currently used to treat acne scars, including medications, photoelectric technology, surgery, filling, chemical peeling, traditional Chinese medicine, biotherapy, and microneedle therapy, and many new methods are constantly emerging. However, there are still many issues, such as the lack of high-quality clinical studies, non-uniform treatment methods, and unsatisfactory therapeutic effects. The selection of appropriate methods for the comprehensive treatment of different types of acne scars at different stages in clinical practice remains challenging and is a research topic of great interest. From the perspective of evidence-based medicine, this consensus aims to provide a reference for the treatment of acne scars in clinical practice. more...

The main etiological mechanism for Kashin-Beck disease (KBD) is deep chondrocyte necrosis induced by environmental risk factors (ERFs). The scholars have conducted several epidemiological, cellular, and animal model studies on ERFs. Gradually, four etiological hypotheses have been formed, including water of organic poisoning hypothesis represented by fulvic acid (FA), biogeochemical hypothesis represented by selenium (Se) deficiency, food mycotoxin poisoning hypothesis represented by T-2 toxin poisoning and compound etiology theory hypothesis. The animal models of KBD have been replicated based on the previous etiological hypotheses. The different species of animals (monkey, rat, dog, pig, chicken, and rabbit) were treated with different ERFs interventions, and the clinical manifestations and pathological changes of articular cartilages were observed. The animals in the experimental group were fed with endemic water, endemic grain, low nutrition, thallium sulfate, FA, Se, T-2 toxin, and iodine. The dose of thallium sulfate was 1154 μg/d; the doses range of FA were 5, 50, 150, 200, and 211 mg/kg; the doses range of Se were 0.00035, 0.00175, 0.005, 0.02, 0.031, 0.1, 0.15, 0.314, 0.5, and 10 mg/kg; the doses range of T-2 toxin were 40, 100, 200, 600, 1000, 1500, 3000, 6000, and 9000 ng/g; and the doses range of iodine were 0.04, 0.18, and 0.4–0.5 μg/g. The sample size ranged from 9 to 230 depending on the interventions and grouping; the follow-up duration ranged from 1 week to 18 months. Moreover, the methods and comparisons of different animal models of KBD had been summarized to provide a useful basis for studying the pathogenesis of KBD. In conclusion, the rhesus monkeys administrated endemic water and grain were susceptible animals to replicate KBD. The rats treated with T-2 toxin combined with Se/nutrition deficiency could be a suitable and widely used animal model. more...

To identify the role of the Hippo signaling pathway in the extracellular matrix degradation of chondrocytes induced by fluoride exposure. Environmental response genes (ERGs) of bone injury induced by fluoride exposure were obtained from the Comparative Toxicogenomics Database, and annotated by STRING for KEGG pathway enrichment analysis. The CCK-8 kit was used to measure the proliferation of ATDC5 cells. The malondialdehyde (MDA), total antioxidant capacity (T-AOC), total superoxide dismutase (T-SOD), and glutathione peroxidase (GSH-PX) levels in ATDC5 cells were measured using oxidative stress detection kit. Western blot analysis was used to measure the p-MST1/2, p-LATS1/2, and p-YAP/YAP1 expression levels in the Hippo pathway and the COL2A1, ACAN and MMP13 expression levels in the cartilage matrix. Localizations of YAP1 and COL2A1 proteins in chondrocytes were performed using cell immunofluorescence. Continuous data from the multiple groups were compared using one-way analysis of variance, and then the differences between groups were tested with Dunnett's t-test, with the test level α = 0.05. The 145 ERGs of bone injury induced by fluoride exposure were identified, and KEGG enrichment analysis revealed Hippo signaling pathways significantly related to bone injury. A CCK-8 assay revealed that the viability of the ATDC5 cells was significantly decreased with increased fluorine concentration. The MDA content in 20 mg/L sodium fluoride (NaF) exposure group was significantly higher than that in the control group, the T-SOD, T-AOC and GSH-PX activities in 15 and 20 mg/L NaF exposure groups were significantly lower than those in the control group (P more...

Background: Oral mucosal melanoma (OMM) is a clinically rare disease with poor prognosis. Various treatment methods have been investigated with the aim of improving the prognosis. This study aimed to analyze the data of a single institution in the management of OMM. Methods: A total of 78 consecutive OMM patients were included in this retrospective study. The intraoral lesion was treated either by cryotherapy, surgery or both; the neck was treated by neck dissection or observation; postoperative chemotherapy with dimethyl triazeno imidazole carboxamide and cisplatin was performed in some patients. The Kaplan-Meier method was used for statistical analysis. Results: Among the 78 patients, there were 50 males and 28 females with an average age of 53.8 years (ranging from 27 to 85 years). The most common sites of OMM were the hard palate and gingiva. The main cause of death in OMM was distant metastasis. No significant difference was found between the intraoral/cervical lesion recurrence/post-operative distant metastasis and the intraoral lesion site/biopsy method/treatment method. The metastasis rate of cervical lymph node was high in the OMM patients, even in the patients with clinically negative necks. Cervical lesion recurrence was correlated with N stage and intraoral lesion recurrence. The survival period was longer in the patients with T3 staging, clinical stage III disease, with post-operative chemotherapy and without post-operative distant metastasis when compared to those patients with T4a staging, clinical stage IV disease, without post-operative chemotherapy and with post-operative distant metastasis. Conclusions: Radical surgery including wide intraoral resection and neck dissection is recommended for OMM patients. Post-operative chemotherapy may also be beneficial for both primary and recurrent OMM patients. [ABSTRACT FROM AUTHOR] more...

The aim of the study was to investigate how mitochondrial fusion/fission contributes to fluoride-induced developmental neurotoxicity and to illuminate the potential mechanism. SH-SY5Y cells were treated with different concentrations of sodium fluoride (NaF, 20, 40, and 60 mg/L) for 24 hr. Meanwhile, a Sprague Dawley (SD) rat model of developmental fluoride exposure from pre-pregnancy until 2 months after delivery was constructed and four groups (n=10) were set up: control group, three NaF-treated groups (NaF was administered at 10, 50, and 100 mg/L via dissolving with tap water). Mdivi-1 and Fis1 overexpression were employed to further explore the role of mitochondrial fission in fluoride-induced mitochondrial dysfunction and cell death. Wortmannin and ACDEVD- CHO were used to test the influence of autophagy and apoptosis on the ultimate cellular viability, respectively. The mitochondrial morphology and function, representative mitochondrial fusion/fission, autophagy and apoptosis proteins, apoptotic rate, and cellular viability were detected. We found that NaF induced dysregulated mitochondrial fission/fusion which was manifested by inhibited fission and accelerated fusion, and was accompanied by mitochondrial heterogeneity and dysfunction such as mitochondrial membrane potential loss and mitochondrial superoxide overproduction in the SH-SY5Y cells. Mechanically, suppressing mitochondrial fission with Mdivi-1 exacerbated the NaF-induced mitochondrial injury and the resultant neuronal death was via excessive apoptosis and promoted autophagy. However, targeting promoting mitochondrial fission by Fis1 overexpression alleviated the NaF-induced detrimental outcomes by inhibiting apoptosis and enhancing autophagy. Furthermore, the promoted autophagy and excessive apoptosis after mitochondrial fission interference were validated to be beneficial and harmful for cellular survival, respectively. Mitochondrial fission reduction and fusion accession occurred consistently in the hippocampus in the NaFexposed offspring rats with cognitive deficits and neuron damage, accompanied by defective autophagy and excessive apoptosis. Taken together, our results suggest that mitochondrial fission inhibition and the subsequent mitochondrial dysfunction trigger defective autophagy and excessive apoptosis contributing to developmental fluoride neurotoxicity. [ABSTRACT FROM AUTHOR] more...

Aim: To test the pathogenicity of pseudorabies virus (PRV) variant HN1201 and compare its pathogenicity with a classical PRV Fa strain., Methods: The pathogenicity of the newly-emerging PRV variant HN1201 was evaluated by different inoculating routes, virus loads, and ages of pigs. The classical PRV Fa strain was then used to compare with HN1201 to determine pathogenicity. Clinical symptoms after virus infection were recorded daily and average daily body weight was used to measure the growth performance of pigs. At necropsy, gross pathology and histopathology were used to evaluate the severity of tissue damage caused by virus infection., Results: The results showed that the efficient infection method of RPV HN1201 was via intranasal inoculation at 10(7) TCID50, and that the virus has high pathogenicity to 35- to 127-d old pigs. Compared with Fa strain, pigs infected with HN1201 showed more severe clinical symptoms and pathological lesions. Immunochemistry results revealed HN1201 had more abundant antigen distribution in extensive organs., Conclusion: All of the above results suggest that PRV variant HN1201 was more pathogenic to pigs than the classical Fa strain. more...