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Head ache within transgender along with gender-diverse patients: A narrative review.
Direct delivery of proteins into cells holds significant potential for basic research and drug development. However, the poor endosomal escape of conventional delivery strategies remains a challenge, thus limiting the clinical translation of many protein therapeutics. Herein, we report that engineered Cry3Aa protein (Pos3Aa) crystals formed naturally within Bacillus thuringiensis can serve as a vehicle for efficient cytosolic delivery of bioactive proteins. We showed that Pos3Aa-mediated delivery of tumor suppressor p53 protein, a promising therapeutic candidate found to be inactivated in nearly half of human cancers, resulted in the restoration of p53 function in p53-deficient cancer cells, and thereby sensitized them to 5-fluorouracil chemotherapy as demonstrated in in vitro and in vivo models. Our results validate that Pos3Aa crystals can be a robust and effective platform for the cytosolic delivery of effector proteins, and suggest that efficient uptake and endosomal escape could be critical for efficacious p53 protein-based cancer therapy.This study was designed to examine the pathophysiological differences in interleukin (IL) and structural protein levels between central nervous system (CNS) disorders associated with heat stroke and CNS stimulants. We measured the concentrations of IL-6, IL-8, neuron-specific enolase (NSE), and myelin basic protein (MBP) in blood and cerebrospinal fluid (CSF) from 87 autopsy cases. In addition, to examine changes in each marker, we cultured nerve cells at 40 °C as a heat stroke model and administered 4-aminopyridine and ephedrine in cultured cells as a CNS stimulant model. IL-6 levels in blood and CSF were significantly higher in the stimulant compared with the heat stroke group. IL-8 levels in blood and CSF were relatively high in the stimulant, heat stroke, and psychotropic addiction groups. NSE levels in blood were high in the stimulant and heat stroke groups, while those in CSF were significantly higher in the heat stroke group. MBP levels in blood were markedly higher in the stimulant and heat stroke groups, but no differences were seen in CSF. Compared with the CNS stimulant model, the heat stroke model with cultured human nerve cells showed high values for each marker. The results of the autopsy and laboratory tests in the present cases and those of cultured cell experiments indicated that CNS disorders caused by CNS stimulants such as amphetamines led to changes in IL-6 as an immune response, which suggests that IL-8 may help protect nerve cells in cases involving heat stroke and stimulants.Pork and pork products are important staple food in the diet of Vietnamese consumers. The safety of pork, including biological contamination, is a concern to several public authorities and value chain actors. This cross-sectional study aimed to identify Salmonella and total bacterial count (TBC) contamination of cut pork sold in different outlets, and determine the potential factors leading to contamination. A total of 671 pork samples were collected from different retail channels in three provinces in Northern Vietnam. Hygiene conditions and practices at pork vending premises were also observed and recorded. Data analysis used descriptive statistics and regression analysis. Overall, Salmonella prevalence in retailed pork was 58.1%. Salmonella contamination in pork from traditional retail, modern retail and food services were 60.5%, 50.9% and 80.5%, respectively. Eighty percent and 68% of fresh pork in canteen and street food was contaminated with Salmonella. Only a small proportion of a subset of the pork samples (6.2%) tested met the Vietnamese standard requirement for TBC contamination. Average concentration of TBC in fresh pork in traditional retail, modern retail and food services were 6.51 (SD 0.64), 6.38 (0.65), and 6.96 (0.85) LogCFU/g, respectively. Transport time, use of the same tools for pork and other types of meat, storage temperature, and environment hygiene are important factors that might affect microbial contamination. The findings underline the high level of microbial contamination, which requires practical interventions to improve food safety hygiene practices and behavior of pork retailers.Bisphenol S (BPS) acts as a xenoestrogen and disturbs the female reproductive system; however, the underlying mechanism has not been elucidated. In this study, the effect of chronic BPS exposure (1 μg/L and 100 μg/L) on ovarian lipid metabolism in zebrafish was investigated to determine its influence on adult reproductive capacity and offspring development. The results showed that long-term (240 days) exposure to BPS induced lipid accumulation in the ovaries by promoting the transport of more lipids from the circulation to the ovaries and by upregulating triacylglycerol synthesis-related genes. Significantly increased expression of cpt2, acadm, acadl, and pparα, which are involved in β-oxidation in the ovarian mitochondria, indicated that more energy was provided for oocyte maturation in exposed zebrafish ovaries. Thus, the proportion of full-grown stage oocytes in ovaries and egg reproduction were elevated at an accelerated rate, which earlier than normal reproductive cycle (8-10 days posts pawning). Tasquinimod Moreover, the maternally BPS-exposed F1 embryos (2 h post-spawning, hpf) showed higher neutral lipid levels, impaired hatching capacity, and increased occurrence of larval deformities. All these findings demonstrated that stimulated lipid synthesis and β-oxidation in zebrafish ovaries significantly contribute to BPS-induced oocyte precociousness with subsequent effects on the development of unexposed offspring. This study provides new insight into the impact of xenoestrogens on oviparous reproduction in females and offspring development from the perspective of ovarian lipid metabolism.Cardiomyocytes differentiated from human induced pluripotent stem cells (hiPSCs) offer tremendous potential when used to engineer human tissues for drug screening and disease modeling; however, phenotypic immaturity reduces assay reliability when translating in vitro results to clinical studies. To address this, we have developed hybrid hydrogels comprised of decellularized porcine myocardial extracellular matrix (dECM) and reduced graphene oxide (rGO) to provide a more instructive microenvironment for proper cell and tissue development. A tissue-specific protein profile was preserved post-decellularization, and through the modulation of rGO content and degree of reduction, the mechanical and electrical properties of the hydrogels could be tuned. Engineered heart tissues (EHTs) generated using dECM-rGO hydrogel scaffolds and hiPSC-derived cardiomyocytes exhibited significantly increased twitch forces and had increased expression of genes that regulate contractile function. Improvements in various aspects of electrophysiological function, such as calcium-handling, action potential duration, and conduction velocity, were also induced by the hybrid biomaterial.
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