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How you can Save a Arm or: Identification associated with Pyoderma Gangrenosum.
Despite reports that quinoline antimalarials including chloroquine (Chq) exhibit idiosyncratic neuropsychiatric effects even at low doses, the drug continues to be in widespread use during pregnancy. Surprisingly, very few studies have examined the potential neurotoxic action of Chq exposure at different points of gestation or how this phenomenon may affect neurophysiological well-being in later life. We therefore studied behavior, and the expression of specific genes and neurochemicals modulating crucial neural processes in offspring of rats exposed to prophylactic dose of Chq during different stages of gestation. Pregnant rats were injected 5 mg/kg/day (3 times) of Chq either during early- (first week), mid- (second week), late- (third week), or throughout- (all weeks) gestation, while controls received PBS injection. Behavioral characterization of offspring between postnatal days 15-20 in the open field, Y-maze, elevated plus and elevated zero mazes revealed that Chq evoked anxiogenic responses and perturb behavioral impairment and neurotoxic changes in rats.Chemotherapy-induced senescent cancer cells secrete several factors in their microenvironment called SASP. Accumulated evidence states that SASP is responsible for some of the harmful effects of chemotherapy such as drug resistance and the induction of cancer cell proliferation, migration, and invasion. Therefore, to develop senolytic and/or senomorphic drugs, targeting the senescent cells gains importance as a new strategy for preventing the damage that senescent cancer cells cause. In the current work, we evaluated whether Rho/Rho kinase pathway has the potential to be used as a target pathway for the development of senolytic and/or senomorphic drugs in doxorubicin-induced senescent cancer cell lines. FM19G11 We have determined that inhibition of Rho/Rho kinase pathway with CT04 and Y27632 reduced the secretory activity of senescent cancer cells and changed the composition of SASP. Our results indicate that ROCK 2 isoform was responsible for these observed effects on the SASP. In addition, non-senescent cancer cell proliferation and migration accelerated by senescent cells were set back to the pre-induction levels after ROCK inhibition. Moreover, contrary to the previous observations, another important finding of the current work is that senescent HeLa and A549 cells did not engulf the non-senescent HeLa, A549 cells, and non-cancer HUVEC. These results indicate that ROCK inhibitors, in particular ROCK 2 specific inhibitors, have the potential to be developed as novel senomorphic drugs. In addition, we found that all senescent cancer cells do not share the same engulfment ability, and this process should not be generalized.Optimal functioning of Sertoli cells is crucial for spermatogenesis which is under tight regulation of sex hormones, estrogen and androgen. Adult rat Sertoli cells expresses estrogen receptor beta (ERβ) and androgen receptor (AR), both of which regulate gene transcription by binding to the DNA. The present study is aimed to acquire a genome-wide map of estrogen- and androgen-regulated genes in adult Sertoli cells. ChIP-Seq was performed for ERβ and AR in Sertoli cells under physiological conditions. 30,859 peaks in ERβ and 9,594 peaks in AR were identified with a fold enrichment >2 fold. Pathway analysis for the genes revealed metabolic pathways to be significantly enriched. Since Sertoli cells have supportive functions and provide energy substrates to germ cells during spermatogenesis, significantly enriched metabolic pathways were explored further. Peaks of the genes involved in lipid metabolism, like fatty acid, glyceride, leucine, and sphingosine metabolism were validated. Motif analysis confirmed the presence of estrogen- and androgen-response elements (EREs and AREs). Moreover, transcript levels of enzymes involved in the lipid metabolic pathways were significantly altered in cultured Sertoli cells treated with estrogen and androgen receptor agonists, demonstrating functional significance of these binding sites. This study elucidates a mechanism by which sex hormones regulate lipid metabolism in Sertoli cells by transcriptionally controlling the expression of these genes, thereby shedding light on the roles of these hormones in male fertility.Massive efforts have been devoted to insulin delivery for diabetes care. Achieving a long-term tight-regulated blood glucose level with a low risk of hypoglycemia remains a great challenge. In this study we propose a novel strategy to efficiently regulate insulin action after insulin is injected or released into patient body aiming to achieve better glycemic control, which is achieved by the administration of insulin-conjugated magnetic nanoparticles (MNPs-Ins). We show that the locomotion of MNPs-Ins can be controlled to reach a target site on an in vitro microfluidic platform, which may open a way to modulate the physiological effect of insulin in a remote-control manner. Most importantly, the in vivo blood glucose regulation of the MNPs-Ins was performed on diabetic mice to understand the glycemic control performance. The results showed that the MNPs-Ins can achieve a better glycemic control with longer effective drug duration while not causing hypoglycemia and a magnetic-modulated hypoglycemic dynamics. Moreover, the in vivo histochemistry experiments confirmed the good biocompatibility of MNPs-Ins. Along with our on-going research on the possibility of the recycle and reuse of the MNPs-Ins, the finding presented in this paper may manifest a fascinating potential in insulin delivery in the near future.Stimuli-responsive drug delivery systems have attracted widespread attention in recent years since they can control drug release in a spatiotemporal manner and can achieve tunable drug release according to patient's physiological or pathological condition. In this review, we briefly introduce the drug delivery barriers and drug delivery systems in the anterior and posterior segment of eyes, and collect the recent advances in stimuli-responsive drug delivery systems in eyes for controlled drug release in response to exogenous stimuli (ultrasound, magnetic stimulus, electrical stimulus, and light) or endogenous stimuli (enzyme, active oxygen species, temperature, ions, and pH). In addition, the design and mechanisms of the stimuli-responsive drug delivery systems have been summarized in this review, and the advantages and limitations are also briefly discussed.
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