The contribution of each factor to stroke severity and outcome is further discussed. Determinant factors in BBB permeability and stroke include mitochondria, miRNAs, matrix metalloproteinases (MMPs), immune cells, cytokines, chemokines, and adhesion proteins. Once these factors are interrogated and their roles in the pathophysiology of stroke are determined, novel targets for drug discovery and development can be uncovered in addition to novel therapeutic avenues for human stroke management.Maple Syrup Urine Disease (MSUD) is an inborn error of metabolism caused by a deficiency of branched α-ketoacid dehydrogenase complex (BCKDC) activity. Branched-chain amino acids (BCAA) accumulation is, at least in part, responsible for neurological disturbances characteristic of this metabolic disorder. Experimental studies demonstrated that high levels of BCAA induce brain oxidative stress. Considering that many antioxidants are obtained from the diet, the dietary restriction in MSUD patients probably produce deficiency of vitamins and micronutrients involved in antioxidant defenses. Supplementation with synthetic melatonin has been used to prevention and treatment of pathological conditions, including brain diseases. In this study, we aimed at investigating the potential neuroprotective effect of melatonin treatment in a MSUD experimental model. Infant rats (7 day old) received twice daily subcutaneous injections of a BCAA pool (0.21472 g/kg, 190 mmol/L leucine, 59 mmol/L isoleucine and 69 mmol/L valine in saline solution (15.8 µL/g per weight/injection) or saline alone, and supplemented with melatonin (10 mg/kg, intraperitoneal) for 21 days. Oxidative stress parameters, i.e. antioxidant enzyme activity, reactive species production and damage to lipids and proteins, were assessed in the cerebral cortex, hippocampus and striatum at twenty-eight days of age. In addition, the damage to blood cell DNA was evaluated. The chronic administration of BCAA pool in infant rats induced significant oxidative stress (p  less then  0.05) - such as oxidation of lipids and proteins, imbalance in antioxidant enzymes activities - damages in DNA (p  less then  0.05) and in brain structures (cerebral cortex, hippocampus and striatum). Notably, melatonin supplementation was able to ameliorate the oxidative (p  less then  0.05) and antioxidant (p  less then  0.05) parameters in the brain and blood of the rat model of MSUD. Our results show that melatonin could be a promising therapeutic agent for MSUD.Vitamin D deficiency has been implicated as a risk factor for autism spectrum disorder (ASD). This case-controlled study was to determine the association between single nucleotide polymorphisms (SNPs) in genes encoding vitamin D metabolism related enzymes and childhood ASD in a Chinese Han population. Both autistic children and age-and gender-matched healthy controls were recruited from September 2012-November 2017. The severity of ASD was evaluated by the childhood autism rating scale (CARS). Taqman probe based real-time PCR was applied to examine genotypes. The association between SNPs and the risk of ASD or the disease severity was examined through the logistic regression. This study recruited 249 children with ASD and 353 healthy controls. The G/A genotype (P = 0.0112) or the G allele (P = 0.0117) of CYP24A1 rs17219315, and the G/A genotype of CYP27B1 rs4646536 (P = 0.0341) were significantly associated with an increased risk of ASD. In addition, multivariate analysis found that A allele of both CYP2R1 rs12794714 (P = 0.0159) and CYP27B1 rs4646536 (P = 0.0268) were significantly associated with the severity of ASD. Genetic polymorphisms in vitamin D metabolism related enzymes are associated with the risk of childhood ASD and the severity of the disease.For therapy of skin cancer, transdermal administration has been a potential way to enhance chemotherapy. However, the drug delivery efficacy remained unsatisfactory because of the physiological barriers from the skin to the tumor, which hindered the effect of 3,5,4'-trimethoxy-trans-stilbene (BTM), a drug that has toxicity to cancer. Herein, we prepared an oil-in-water (O/W) microemulsion to load BTM (BTM-ME) for transdermal therapy of melanoma. BTM-ME was characterized by size, zeta potential, and polymer disperse index (PDI). B16F10 melanoma cell line was used for cell experiments and animal models. And cell uptake, viability assay, and flow cytometry were to test the cell internalization and the ability of BTM-ME to induce cancer cell apoptosis. Skin penetration testing was to detect its penetration efficiency to the skin. And tumor-bearing mice were used to prove the improvement of anti-cancer efficacy of BTM-ME with the combination of Taxol. BTM was successfully loaded in O/W microemulsion, with a drug loading capacity of 24.82 mg/mL. BTM-ME can penetrate the skin and increase the retention of BTM in the epidermis. And the combination of Taxol and BTM-ME effectively suppressed tumor growth and has lower toxicity to normal organs. BTM-ME provides adjuvant therapy to cutaneous melanoma and the combination of Taxol and BTM-ME has the clinical potential for skin cancer therapy. Graphical abstract.Alzheimer disease (AD) is very common among the older people. Midostaurin cell line There are few medications available as oral and suspension dosage forms for the management of AD. Due to the rising cases of AD and the associated risks of the existing line of treatment, oil in water (o/w) nanoemulsion (NE) loaded with donepezil was prepared to explore intranasal route of administration. The NE was prepared using labrasol (10%), cetyl pyridinium chloride (1% in 80% water), and glycerol (10%), with a drug concentration of 1 mg/ml. The developed NE was characterized for particle size, polydispersity index (PDI), and zeta potential. In vitro release studies were conducted to observe the release of drug. Further in vivo studies of developed NE were done on Sprague Dawley rats using technetium pertechnetate (99mTc) labeled formulations to investigate the nose to brain drug delivery pathway. The nanoemulsion showed particle size of 65.36 nm with a PDI of 0.084 and zeta potential of -10.7 mV. In vitro release studies showed maximum release of 99.