Patients undergoing chemotherapy with cisplatin commonly present gastrointestinal effects such as constipation and gastric emptying (GE) delay. Both the purinergic system and physical exercise modulate the gastrointestinal (GI) tract. In the current study, we investigated the role of ATP, physical exercise, and P2X7 receptor blocking on GE delay induced by cisplatin in rats. Male rats were divided into the following groups: control (C), cisplatin (Cis), exercise (Ex), Brilliant Blue G (BBG), ATP, Cis+Ex, Cis+ATP, Cis+BBG, Cis+Ex+BBG, Cis+Ex+BBG+ATP, and Cis+ATP+BBG. GE delay was induced by treatment with 1 mg/kg cisplatin (1 time/week for 5 weeks, ip). The moderate physical exercise was swimming (1 h/day, 5 days/week for 5 weeks). At the end of the treatment or exercise and 30 min before the GE assessment, some groups received BBG (50 mg/kg, sc) or ATP (2 mg/kg, sc). Then, GE was assessed after a 10-min postprandial period. Chronic use of Cis decreased GE delay (P<0.05) compared to the control group. Both exercise and ATP prevented (P<0.05) GE delay compared to Cis. The pretreatment with BBG significantly inhibited (P<0.05) the effect of exercise and ATP. On the other hand, the association between exercise and ATP reversed (P<0.05) the effect of the BBG and prevented GE delay. Therefore, we suggest that both exercise and treatment with ATP activate P2X7 receptors and prevent GE delay induced by cisplatin in rats.

The LW-9 peptide was previously identified through screening of purified molecules from the venom of the spider Phoneutria nigriventer and has been described as an immunomodulatory compound with potential application in cancer therapy. The molecule was biochemically characterized and subjected to in silico analyses to evaluate its toxicity and efficacy profiles. LW-9 exhibits a molecular mass of 1235.522 Da and the amino acid sequence PyrKKDRFLGLM-CONH₂. Secondary and tertiary structures were modeled using computational approaches. The results indicated low permeability across biological membranes, including the blood–brain barrier. In silico predictions further suggested that LW-9 is neither carcinogenic nor mutagenic; however, it may act as a potent inhibitor of the CYP3A4 enzyme, raising concerns regarding potential drug–drug interactions. Overall, LW-9 shows promise as an immunomodulatory agent for cancer applications, while its pharmacokinetic properties and possible interactions with other drugs continue to be investigated.

Dados obtidos em 195 países no ano de 2017 revelaram que a asma atingiu 43,12 milhões de novos casos/ano e para o tratamento dessa patologia utilizam-se medicações anti-inflamatórias, anti-histamínicas e às vezes plantas medicinais, como o gengibre (Zingiber officinale Roscoe). O objetivo desse estudo foi analisar o perfil farmacológico e toxicológico, in silico, dos principais compostos secundários do Zingiber officinale Roscoe e as interações moleculares com alvos farmacológicos de importância no processo inflamatório. Para tal, buscou-se por estruturas químicas e atividades dos compostos com evidência científica, avaliações farmacocinéticas e toxicológicas, in silico, em servidores online, bem como docking molecular. Foram utilizadas 12 moléculas, com destaque para os gingeróis, paradol e shogaóis, por serem os principais compostos do rizoma em quantidade e ação farmacológica, os quais apresentaram porcentagem relevante de afinidade pela 5LOX, segundo a plataforma SwissTarget Prediction. Observou-se, também, pela plataforma preADMET, capacidade em atravessar a barreira hematoencefálica e absorção intestinal favoráveis e, alta ligação às proteínas plasmáticas. Além disso, os principais compostos secundários não inibiram o CYP3A4, não apresentaram potencial mutagênico no Teste de Ames, apresentaram moderadas e baixas DL50 e baixo índice arritmogênico, além de moderada probabilidade de carcinogenicidade, mutagenicidade, nefrotoxicidade e toxicidade no sistema respiratório pelo ProTox III. O compostos secundários 6-shogaol e o 6-paradol apresentaram maior probabilidade de ligação o alvo 5LOX e demonstraram, estatisticamente, ancoragem semelhante ao zileuton, propriedades físico-químicas e farmacocinéticas favoráveis para uso oral, além do perfil menos tóxico quando comparado aos demais compostos, embora possuam potencial imunotóxico e potencial carcinogênico em camundongos.

Acute respiratory distress syndrome (ARDS) is a life-threatening inflammatory condition characterized by high morbidity and mortality, with limited effective pharmacological therapies currently available. The search for novel compounds with anti-inflammatory and antioxidant properties remains essential to improve clinical outcomes. In this context, Pentyl (2E)-3-(3-methoxyphenyl)prop-2-enoate (MAP), a phenolic cinnamic acid derivative, emerges as a promising candidate due to its potential biological activities. This study aimed to investigate the anti-inflammatory effects of MAP using an integrative approach combining in silico and in vivo analyses. Initially, pharmacokinetic and toxicological predictions indicated favorable oral bioavailability, adequate distribution, low predicted toxicity, and compliance with Lipinski’s rules. Molecular docking studies demonstrated significant interactions with key inflammation-related targets, while density functional theory (DFT) calculations revealed electronic stability and favorable orbital distribution. Additionally, molecular dynamics simulations confirmed the stability of ligand–protein complexes, with low root mean square deviation (RMSD) values over time. Subsequently, the in vivo effects of MAP were evaluated in a rat model of intestinal ischemia–reperfusion (iI/R)-induced ARDS. Oral administration of MAP (20, 40, or 60 mg/kg) significantly reduced leukocyte infiltration, oxidative stress markers, and pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6) while attenuating histopathological lung damage. Furthermore, MAP enhanced antioxidant defenses by increasing glutathione levels and catalase activity, alongside reducing nitric oxide production. Importantly, no evidence of acute genotoxicity was observed at the tested doses. In summary, MAP demonstrated consistent anti-inflammatory and antioxidant effects across computational and experimental models, effectively mitigating key pathological features of ARDS. These findings suggest that MAP is a promising adjuvant therapeutic candidate for acute respiratory inflammatory conditions, although further studies are necessary to elucidate its mechanisms of action and support its potential clinical application. Graphical Abstract

Background/Objectives: Chronic complications of diabetes mellitus are closely associated with increased oxidative stress and the formation of advanced glycation end products (AGEs). This study aimed to investigate the antioxidant and antiglycation potential of hesperetin-7-O-glucoside (HCD) and diosmetin-7-O-glucoside (DCD) formulations complexed with cyclodextrins, using in vitro and in silico experimental models to evaluate their efficacy in mitigating hyperglycemia-induced molecular damage. Methods: Antioxidant activity was assessed using chemical and erythrocyte-based oxidative stress models, whereas antiglycation activity was evaluated in BSA–fructose, BSA–methylglyoxal, and arginine–methylglyoxal models. Results: Both formulations showed measurable antioxidant effects, with concentration-dependent behavior observed in some of the evaluated assays. In the DPPH assay, HCD and DCD achieved maximum inhibition values of 30.71% and 26.61%, respectively. Furthermore, DCD exhibited higher total antioxidant capacity (102.80 µg vitamin C equivalents/mL) and nitric oxide scavenging activity (37.89%) than HCD. In a cellular model, both formulations (200 µg/mL) significantly reduced AAPH-induced hemolysis, with DCD providing superior protection (7.05% vs. 16.63% for HCD). Under oxidative stress induced by high glucose concentration in erythrocytes, HCD and DCD reduced non-protein thiol levels, and HCD significantly increased catalase enzyme activity. Regarding antiglycation activity, DCD demonstrated superior efficacy relative to HCD in the BSA-fructose system, achieving 43.23% inhibition. DCD also displayed concentration-dependent inhibition of fructosamine formation (up to 47.99%) and BSA glycation by methylglyoxal (up to 45.20%). Both formulations significantly reduced carbonylated protein levels and preserved free thiol groups. In the arginine–methylglyoxal model, DCD and HCD reached 44.03% and 48.82% inhibition, respectively. Molecular docking revealed high binding affinity of both flavonoids to the protein active site (−9.00 kcal/mol for hesperetin-7-O-glucoside and −9.04 kcal/mol for diosmetin-7-O-glucoside), suggesting a structural protective role. Conclusions: The HCD and DCD formulations demonstrated antioxidant and antiglycation activities that may contribute to attenuating molecular alterations associated with chronic hyperglycemia through complementary mechanisms, including antioxidant effects, protection against protein carbonylation, and inhibition of glycation. While these findings highlight the potential of the evaluated formulations, additional mechanistic and in vivo studies are required to establish their pharmacological applicability.

O câncer de pele não melanoma (CPNM) é o tipo de câncer com maior incidência e tem sido classificado em: carcinoma basocelular (CBC) e carcinoma espinocelular (CEC). O objetivo do presente estudo foi avaliar, por meio de uma revisão bibliográfica integrativa, a utilização de lipossomas no diagnóstico e tratamento de CPNM. A estratégia de busca dos artigos científicos foi realizada através de uma investigação nas bases de dados Scopus, Pubmed e Web Of Science, acessando através do Portal Periódicos Capes, utilizando os descritores em inglês “Liposomes” AND “non-melanoma” AND “skin” AND “cancer” AND “(treatment OR diagnosis)”. Para auxiliar o processo de análise dos artigos, utilizou-se a plataforma Rayyan. Após análise, 7 publicações foram selecionadas para compor essa revisão, identificando: títulos, autores, objetivos, principais resultados, conclusões e temas abordados nos estudos. Observou-se que a maioria dos eixos temáticos abordaram a utilização de sistemas lipossomais para a potencialização de drogas com capacidade antitumoral. Os demais artigos discorriam sobre a utilização na detecção e diagnóstico das lesões associadas ao Câncer de Pele Não Melanoma e, também, a aplicação de nanocarreadores em terapias anticâncer, sobretudo na terapia fotodinâmica. Baseado nisso, concluiu-se que os lipossomas possuem uma aplicação versátil no CPNM, indo do tratamento ao diagnóstico, no entanto, as pesquisas acerca da aplicação voltada para esse tema, são escassas e recentes. Dessa forma, esta revisão é de extrema relevância para que se possa direcionar a elaboração de novos estudos que visem aprimorar técnicas já mencionadas e desenvolver novas pesquisas acerca do tema.