Fluoride-Induced Expression of Neuroinflammatory Markers and Neurophysiological Regulation in the Brain of Wistar Rat Model.

Excess fluoride intake has been linked with various pathological conditions. The objective of the present study was to understand the role of fluoride in neurotoxic, neuroinflammatory, and neurodegenerative changes in the brain tissue of Wistar rats. Wistar rats were fed with water containing 20-100 ppm (ppm) sodium fluoride (NaF). An array of neurotransmitters (acetylcholine, dopamine, epinephrine, norepinephrine, serotonin, histamine, and glutamate) expression levels were estimated with respect to different fluoride concentrations. Additionally, its effect on the expression levels of specific neuroinflammatory markers (iNOS, COX-2, TNF-α, PKC, VEGF, and HSP-70) in brain tissues of Wister rats was assessed. An increase in NaF concentration resulted in increased fluoride deposition in the brain which in turn caused increase levels of epinephrine, histamine, serotonin, and glutamate and decreased levels of norepinephrine, acetylcholine, and dopamine in a dose-dependent manner. Tissue fluoride levels of the hippocampus, neocortex, cerebellum, spinal cord, and sciatic nerve increased significantly in fluoride fed rats. Transmission electron microscopy in the experimental animals revealed axon deterioration, myelin sheath degeneration, and dark cells with scanty cytoplasm in the spinal cord and sciatic nerve. Additionally, vacuolated swollen mitochondria were observed in the neocortex, hippocampus, and cerebellum. Results suggest excess fluoride intake modulates a set of biological marker and promote neuroinflammatory and neurodegenerative condition in Wister rats. Therefore, we conclude that the accumulation of NaF alters the neurological function which leads to neurodegenerative disorders.

Efficacy and safety of neural stem cell therapy for spinal cord injury: A systematic literature review.

AIMS: To summarize the evidence on the efficacy and safety of neural stem cell therapy (NSCT) for the treatment of spinal cord injury (SCI). METHODS: A systematic literature review of Medline®, EMBASE® and Cochrane library was performed to identify studies reporting efficacy and safety of NSCT in SCI. Articles were included if they reported efficacy and safety data of SCI patients who received NSCT. RESULTS: Overall, four studies of the 277 records met all the study eligibility criteria. Over the 1-year follow-up period, motor scores were significantly higher among patients who received NSCT compared with those who did not (American Spinal Injury Association [ASIA] motor scores (mean±standard deviation [SD]): 7.9±1.2 versus 3.9±0.6; upper extremity motor score: 7.8±2.1 versus 3.9±0.6, both P<0.05). Sensory scores (pinprick score: 4.8±1.3 versus 2.9±0.6; P=0.5; light touch score: 6.9±3.1 versus 2.3±0.5, P=0.3), ASIA impairment scale (26% versus 7%) or pain score (baseline: 2.4±0.6; 1-year: 3.4±0.4) were comparable in both NSCT and non-NSCT cohorts. Over the 1-year follow-up period, the graded redefined assessment of strength, sensibility, and prehension and international standards for neurological classification of SCI scores showed a mean improvement of 14.8 and 17.8 points respectively. Overall, treatment with NSCT showed favorable safety and tolerability profile. CONCLUSIONS: Due to the limited and poor-quality evidence, it is too early to make robust conclusions on the efficacy of NSCT in the treatment of SCI. However, based on the included studies, NSCT seems to be a potential option worth exploring among patients with SCI. Nonetheless, prospective, randomized trials in larger cohorts are needed to validate the efficacy and safety of NSCT in the treatment of SCI.

Current State and Future of Private Practice Nephrology in the United States.

Chronic kidney disease remains highly prevalent and exerts a heavy economic burden. The practice of nephrology has come a long way in managing this disease, though there remains room for improvement. The private domain, where more than half of the adult nephrology workforce operates, faces serious challenges. Interest has decreased in the field, leading to diminished recruitment. There has been a reduction in both reimbursement rates and revenues. We discuss the current state of private practice nephrology and strategies to reinvigorate our discipline. There needs to be a focus on preparing fellows during training not only for academic careers, but also for effective functioning in the environment of private practice and development of pathways for growth. We believe that private practice nephrology must expand its frontiers to be fulfilling professionally, challenging academically, and successful financially. The United States government has recently announced the Advancing American Kidney Health Executive Order which seeks to prioritize optimal treatments for patients with kidney disease. We are optimistic that there is a renaissance afoot in nephrology and that our field is in the process of rediscovering itself, with its best days yet to come.

Applications of in silico methods to analyze the toxicity and estrogen receptor-mediated properties of plant-derived phytochemicals.

A myriad of phytochemicals may have potential to lead toxicity and endocrine disruption effects by interfering with nuclear hormone receptors. In this examination, the toxicity and estrogen receptor-binding abilities of a set of 2826 phytochemicals were evaluated. The endpoints mutagenicity, carcinogenicity (both CAESAR and ISS models), developmental toxicity, skin sensitization and estrogen receptor relative binding affinity (ER_RBA) were studied using the VEGA QSAR modeling package. Alongside the predictions, models were providing possible information for applicability domains and most similar compounds as similarity sets from their training sets. This information was subjected to perform the clustering and classification of chemicals using Self-Organizing Maps. The identified clusters and their respective indicators were considered as potential hotspot structures for the specified data set analysis. Molecular screening interpretations of models were exhibited accurate predictions. Moreover, the indication sets were defined significant clusters and cluster indicators with probable prediction labels (precision). Accordingly, developed QSAR models showed good predictive abilities and robustness, which observed from applicability domains, representation spaces, clustering and classification schemes. Furthermore, the designed new path could be useful as a valuable approach to determine toxicity levels of phytochemicals and other environmental pollutants and protect the human health.

Haplotype analyses of DNA repair gene polymorphisms and their role in ulcerative colitis.

Ulcerative colitis (UC) is a major clinical form of inflammatory bowel disease. UC is characterized by mucosal inflammation limited to the colon, always involving the rectum and a variable extent of the more proximal colon in a continuous manner. Genetic variations in DNA repair genes may influence the extent of repair functions, DNA damage, and thus the manifestations of UC. This study thus evaluated the role of polymorphisms of the genes involved in DNA repair mechanisms. A total of 171 patients and 213 controls were included. Genotyping was carried out by ARMS PCR and PCR-RFLP analyses for RAD51, XRCC3 and hMSH2 gene polymorphisms. Allelic and genotypic frequencies were computed in both control & patient groups and data was analyzed using appropriate statistical tests. The frequency of 'A' allele of hMSH2 in the UC group caused statistically significant increased risk for UC compared to controls (OR 1.64, 95% CI 1.16-2.31, p = 0.004). Similarly, the CT genotype of XRCC3 gene was predominant in the UC group and increased the risk for UC by 1.75 fold compared to controls (OR 1.75, 95% CI 1.15-2.67, p = 0.03), further confirming the risk of 'T' allele in UC. The GC genotype frequency of RAD51 gene was significantly increased (p = 0.02) in the UC group (50.3%) compared to controls (38%). The GC genotype significantly increased the risk for UC compared to GG genotype by 1.73 fold (OR 1.73, 95% CI 1.14-2.62, p = 0.02) confirming the strong association of 'C' allele with UC. Among the controls, the SNP loci combination of hMSH2:XRCC3 were in perfect linkage. The GTC and ACC haplotypes were found to be predominant in UC than controls with a 2.28 and 2.93 fold significant increase risk of UC.