Mechanism-based therapeutic targets of pemphigus vulgaris: A scoping review of pathogenic molecular pathways.

Pemphigus vulgaris (PV) is a potentially fatal autoimmune blistering disease characterised by cell-cell detachment or acantholysis. The mechanisms which follow antibody (Ab) binding and culminate in acantholytic changes and skin/mucosal blistering have not been fully clarified. Current treatment strategies are not specific to PV pathophysiology and although life-saving, harbour considerable side effects. We aimed to systematically assess the molecules amenable to targeted treatments that follow Ab binding and are associated with PV acantholysis. The resulting scoping review was conducted under PRISMA-ScR guidelines with clear inclusion and exclusion criteria and focused specifically on kinases, caspases, proteases, hydrolytic enzymes and other molecules of interest postulated to take part in the pathophysiology of PV. The review process resulted in the identification of 882 articles, of which 56 were eligible for qualitative synthesis. From the included articles, the majority (n = 42) used PV-IgG as the pathogenic agent, mainly via in vitro (n = 16) and in vivo (n = 10) models. Twenty-five molecules were found to play a pathogenic role in PV, including uPA, ADAM10, EGFR, Src, PKC, cdk2, ERK, PLC, calmodulin, NOS, p38MAPK and caspase-3. Selective inhibition of these molecules resulted in varying degrees of reduction in acantholysis and blistering. The pathogenic molecules identified in this review represent potential candidates for clinical translation.

Starch engineered with Moringa oleifera seeds protein crosslinked Fe3O4: A synthesis and flocculation studies.

This study aimed to utilize cationic protein extracted from the Moringa oleifera seed in the fabrication of cationic starch crosslinked with magnetic nanoparticles (MagCS). Important synthesis parameters include starch to cationic protein volume ratio, magnetic nanoparticles mass fraction, reaction and crosslinking time, reaction and crosslinking temperature and crosslinker concentration. At optimum synthesis conditions, MagCS yield a 38.55% amide content, 2.46 degree of substitution, 1.1 mmol/g charge density and 78.6% crosslinking, which are much higher compared to other starch derivatives. A series of characterization analyses such as Fourier transform infrared spectroscopy, X-ray diffraction, thermogravimetric analysis, elemental analysis and vibrating sample magnetometer concluded that MagCS was embedded with amide group, has high crystallinity structure, is thermally stable and shows a promising magnetic characteristic. Based on the synthesis parameters and characterization studies, the synthesis mechanism of MagCS was also postulated. The flocculation performance of MagCS was successfully assessed for the treatment of palm oil mill effluent. At optimum dosage, initial pH and settling time of 1.0 g/L, 9.0 and 15 min, the MagCS flocculant was able to remove 90.48, 83.95 and 58.19% of turbidity, color and chemical oxygen demand, respectively. This study provides an alternative eco-friendly materials in the wastewater treatment application.

Low-dose Nicotine Exposure Induced the Oxidative Damage of Reproductive Organs and Altered the Sperm Characteristics of Adolescent Male Rats.

BACKGROUND: Nicotine is a major toxic and hazardous component of cigarette smoke, and it has been widely used in nicotine replacement therapy (NRT). This study was aimed to investigate the effects of chronic low-dose nicotine on sperm characteristics and reproductive organ integrity in adolescent male Sprague-Dawley rats. METHODS: Twelve rats were equally divided into two groups. Group I received normal saline, and group II received 0.6 mg/kg body weight nicotine intraperitoneally for 28 consecutive days. At the end of the experimental period, sperm was collected for sperm characteristic evaluation, and the testes and prostate were isolated for biochemical and morphological analysis. The effects of nicotine on the body and reproductive organ weights of the animals were evaluated. RESULTS: Chronic nicotine treatment significantly (P < 0.05) altered the sperm count, motility, viability, and morphology, and remarkably increased the malondialdehyde (P < 0.001) and advanced oxidation protein product (P < 0.05) levels in the testes and prostate of nicotine-treated group compared to control group. Moreover, nicotine caused a significant decrease (P < 0.05) in the superoxide dismutase activity of the testes. No significant differences were observed in the reduced glutathione level in both of the testes and prostate of nicotine group compared with control group. Nicotine also induced histopathological alteration in the testes. CONCLUSION: A low-dose nicotine exposure at 0.6 mg/kg caused detrimental effects on sperm characteristics and induced oxidative stress in the testes and prostate.