Synaptic transmission is critically dependent on synaptic vesicle (SV) recycling. Although the precise mechanisms of SV retrieval are still debated, it is widely accepted that a fundamental role is played by clathrin-mediated endocytosis, a form of endocytosis that capitalizes on the clathrin/adaptor protein complex 2 (AP2) coat and several accessory factors. Here, we show that the previously uncharacterized protein KIAA1107, predicted by bioinformatics analysis to be involved in the SV cycle, is an AP2-interacting clathrin-endocytosis protein (APache). We found that APache is highly enriched in the CNS and is associated with clathrin-coated vesicles via interaction with AP2. APache-silenced neurons exhibit a severe impairment of maturation at early developmental stages, reduced SV density, enlarged endosome-like structures, and defects in synaptic transmission, consistent with an impaired clathrin/AP2-mediated SV recycling. Our data implicate APache as an actor in the complex regulation of SV trafficking, neuronal development, and synaptic plasticity.

Sugar-induced metabolic imbalances are a major health problem since an excessive consumption of saccharides has been linked to greater obesity rates at a global level. Sucrose, a disaccharide composed of 50% glucose and 50% fructose, is commonly used in the food industry and found in a range of fast, restaurant, and processed foods. Herein, we investigated the effects of a TRPC4/TRPC5 blocker, ML204, in the metabolic imbalances triggered by early exposure to sucrose-enriched diet in mice. TRPC4 and TRPC5 belong to the family of non-selective Ca⁺² channels known as transient receptor potential channels. High-sucrose (HS)-fed animals with hyperglycaemia and dyslipidaemia, were accompanied by increased body mass index. mesenteric adipose tissue accumulation with larger diameter cells and hepatic steatosis in comparison to those fed normal diet. HS mice also exhibited enhanced adipose, liver, and pancreas TNFα and VEGF levels. ML204 exacerbated hyperglycaemia, dyslipidaemia, fat tissue deposition, hepatic steatosis, and adipose tissue and liver TNFα in HS-fed mice. Normal mice treated with the blocker had greater hepatic steatosis and adipose tissue cell numbers/diameter than those receiving vehicle, but showed no significant changes in tissue inflammation, glucose, and lipid levels. The results indicate that TRPC4/TRPC5 protect against the metabolic imbalances caused by HS ingestion.

Metabolic dysfunctions, such as hyperglycemia and insulin resistance, have been associated to cognitive impairment and dementia regardless of advanced age, although the underlying mechanisms are still elusive. Thus, this study investigates the deleterious effects of metabolic syndrome (MetS) induced by long-term exposure to a high-sucrose diet on motor and cognitive functions of male adult rats and its relationship with hippocampal endoplasmic reticulum (ER) stress. Weaned Wistar male rats were fed a high-sucrose diet until adulthood (HSD; 6 months old) and compared to both age-matched (CTR; 6 months old) and middle-aged chow-fed rats (OLD; 20 months old). MetS development, serum redox profile, behavioral, motor, and cognitive functions, and hippocampal gene/protein expressions for ER stress pro-adaptive and pro-apoptotic pathways, as well as senescence markers were assessed. Prolonged exposure to HSD induced MetS hallmarked by body weight gain associated to central obesity, hypertriglyceridemia, insulin resistance, and oxidative stress. Furthermore, HSD rats showed motor and cognitive decline similar to that in OLD animals. Noteworthy, HSD rats presented marked hippocampal ER stress characterized by failure of pro-adaptive signaling and increased expression of Chop, p21, and Parp-1 cleavage, markers of cell death and aging. This panorama resembles that found in OLD rats. In toto, our data showed that early and sustained exposure to a high-sucrose diet induced MetS, which subsequently led to hippocampus homeostasis disruption and premature impairment of motor and cognitive functions in adult rats.

Aim: The present study aimed to verify whether the consumption of higher doses of whey proteins present changes in liver biomarkers and in the feed intake in sedentary Wistar rats compared to lower doses. Materials and Methods: This is an experimental study, the study was carried out with 32 rats that were allocated in four groups: C - non-supplemented control (n = 10), S2 - supplemented with 2g/kg/day (n = 10), S4 - supplemented with 4g/kg/day (n = 7), S6 - supplemented with 6g/kg/day (n = 5) by gavage and supplemented with whey proteins. Bilirubin and Albumin biomarkers will be analyzed. Results: Regarding total proteins, significant differences were found between groups C and W6 (p = 0.0282) and between groups W2 and W6 (p = 0.0054). For Bilirubin significant differences were found only between groups W2 and W6 (p = 0.0213). Main Conclusions: The findings of this study suggest that doses of 2, 4 and 6g/kg/day of whey proteins do not influence the alteration of liver biomarkers, constituting a hepatoprotective supplement and as the dosage of supplementation increases, there is a reduction in feed consumption, suggesting that whey protein supplementation may regulate rat food intake.

Diabetes mellitus (DM) is a metabolic disorder characterized by chronic hyperglycemia that disrupts skin repair through alterations in tissue biochemical composition and structural organization. This study compared Raman spectral profiles of normal and healed skin tissue in non-diabetic (Non-Db) and diabetic (Db) Wistar rats, based on the hypothesis that diabetes alters skin molecular composition during healing. Twelve Wistar rats were divided into Non-Db and Db groups ( n = 6 per group). DM was induced by of alloxan monohydrate injection (150 mg/kg). Dorsal skin excision was performed under anesthesia on day 0 (normal tissue) and day 14 (healed tissue), resulting in 24 samples. Raman spectra were acquired (830 nm excitation, 400–1800 cm ^–1 range, ~ 4 cm ^–1 resolution, 30 s integration time) in sextuplicate per sample. Data were analyzed by principal component analysis (PCA), followed by ANOVA or Kruskal-Wallis tests. The Raman spectra mainly characterized by features attributed to structural proteins and lipids from epidermal and dermal layers, including collagen, elastin, keratin, and amino acids, fatty acids, ceramides, phospholipids and cholesterol. PCA revealed group-dependent variations in protein- and lipid-associated bands. Increased in protein related features accompanied by a relative reduction in lipids contributions suggested disruption of protein-lipid balance during extracellular matrix remodeling, suggesting molecular alterations in healed skin tissue associated with DM. Raman spectroscopy showed changes in the biomolecular profile of skin healing in diabetic tissue compared with non-diabetic, evidencing a distinct repair pattern marked by modified collagen related features and enhanced membrane lipid signatures in healed diabetic skin.

Publicado em 23 de maio de 2023. A obra "Farmácia: Pesquisa, produção e difusão de conhecimentos 2" que tem como foco principal a apresentação de trabalhos científicos diversos que compõe seus 09 capítulos, relacionados às Ciências Farmacêuticas e Ciências da Saúde. A obra abordará de forma interdisciplinar trabalhos originais e revisões com temáticas nas diversas áreas de atuação do profissional Farmacêutico nos diferentes níveis de atenção à saúde. O objetivo central foi apresentar de forma sistematizada e objetivo estudos desenvolvidos em diversas instituições de ensino e pesquisa do país. Em todos esses trabalhos a linha condutora foi o aspecto relacionado à atenção e assistência farmacêutica, microbiologia, farmacologia, entre outras áreas. Estudos com este perfil podem nortear novas pesquisas na grande área das Ciências Farmacêuticas. Temas diversos e interessantes são, deste modo, discutidos aqui com a proposta de fundamentar o conhecimento de acadêmicos, mestres e todos aqueles que de alguma forma se interessam pelas Ciências Farmacêuticas, apresentando artigos que apresentam estratégias, abordagens e experiências com dados de regiões específicas do país, o que é muito relevante, assim como abordar temas atuais e de interesse direto da sociedade. Deste modo a obra "Farmácia: Pesquisa, produção e difusão de conhecimentos 2" apresenta resultados obtidos pelos pesquisadores que, de forma qualificada desenvolveram seus trabalhos que aqui serão apresentados de maneira concisa e didática. Sabemos o quão importante é a divulgação científica, por isso evidenciamos também a estrutura da Atena Editora capaz de oferecer uma plataforma consolidada e confiável para estes pesquisadores exporem e divulguem seus resultados. Boa leitura! Débora Luana Ribeiro Pessoa