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Braz. J. Med. Biol. Res. [JOURNAL]

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Revealing induced pluripotent stem cells' potential as a better alternative to embryonic stem cells for Parkinson's disease treatment based on single-cell RNA-seq.

Zhang S, Jiang X, Yan M … +5 more , Cheng Z, Bi J, Wang Q, Luo Y, Tian X

Braz J Med Biol Res · 2024 · PMID 39699375 · Full text

Both embryonic stem cells (ESCs) and the successful reprogramming of induced pluripotent stem cells (iPSCs) offer an unprecedented therapeutic potential for Parkinson's disease (PD), allowing for the replacement of deple... Both embryonic stem cells (ESCs) and the successful reprogramming of induced pluripotent stem cells (iPSCs) offer an unprecedented therapeutic potential for Parkinson's disease (PD), allowing for the replacement of depleted neurons in PD-affected brain regions, thereby achieving therapeutic goals. This study explored the differences in cell types between iPSCs and ESCs in the PD brain to provide a feasible theoretical basis for the improved use of iPSCs as a replacement for ESCs in treating PD. Signal cell RNA sequencing data and microarray data of ESCs and iPSCs were collected from the GEO database. scRNA-seq data were subjected to quality control, clustering, and identification using the Seurat R package to determine cell types and proportions in ESCs and iPSCs. Differential expression analysis was performed to identify differentially expressed genes between ESCs and iPSCs, and PPI network analysis was conducted using String. Based on scRNA-seq data, we identified 13 cell clusters in ESCs and 13 cell clusters in iPSCs. iPSCs were predominantly composed of immune cells and lacked astrocytes, neurons, and dopamine neurons compared to ESCs. iPSCs also exhibited lower cell type diversity compared to ESCs. At the gene level, iPSCs lacked key genes, such as TH and GAP43 for nerve growth and development. At the metabolic level, the difference between ESCs and iPSC was mainly reflected in nerve cells and was closely related to the tumor-proliferation signature. iPSCs can be promoted to differentiate into cell types closer to or even replace ESCs, providing a better therapeutic option for PD treatment.

Erratum notice for: "Unlocking the molecular realm: advanced approaches for identifying clinically and environmentally relevant bacteria" [Braz J Med Biol Res 2023: 56, e12894].

Braz J Med Biol Res · 2024 Dec · PMID 39630810 · Full text

[This corrects the article doi: 10.1590/1414-431X2023e12894]. [This corrects the article doi: 10.1590/1414-431X2023e12894].

Deoxycholic acid aggravates necrotizing enterocolitis through downregulation of mesenchymal-epithelial transition factor expression.

Li H, Lai J, Xiao D … +5 more , Huang D, Zhang Y, Gu X, Li F, Hao H

Braz J Med Biol Res · 2024 · PMID 39630809 · Full text

Bile acids are closely associated with necrotizing enterocolitis (NEC), and their accumulation has cytotoxic effects on cells. However, the specific bile acid subtype involved in NEC and its underlying mechanisms remains... Bile acids are closely associated with necrotizing enterocolitis (NEC), and their accumulation has cytotoxic effects on cells. However, the specific bile acid subtype involved in NEC and its underlying mechanisms remains poorly understood, limiting the therapeutic potential of bile acids as treatment targets. In the present study, deoxycholic acid (DCA) accumulation in the intestinal lumen exacerbated NEC-induced intestinal damage. DCA suppressed the expression of mesenchymal-epithelial transition factor (MET), a proto-oncogene located on chromosome 7q31.2 that encodes c-Met, in the mouse intestine through transcription factors and increased nuclear translocation of p-STAT3. MET is a receptor tyrosine kinase that participates in cell proliferation and migration processes. Increasing concentrations of DCA downregulated MET expression and reduced the proliferation and migration of intestinal epithelial cells in vitro. MET knockdown reduced the proliferation and migration of intestinal epithelial cells but increased STAT3 phosphorylation. These findings indicated that MET mediated STAT3 involvement in intestinal epithelial cell proliferation and migration, demonstrating that the inhibitory effect of DCA on MET disrupted this process. These results elucidated the damaging effects and mechanisms of DCA accumulation in NEC, providing new insights into the use of DCA as a therapeutic target for NEC.

Effects of imposed and self-selected exercise on perceptual and affective responses, muscle function, quality, and functionality of strength training in older women and men: a randomized trial.

Garcia EDSA, Ferreira SS, Lazzarotto R … +2 more , Silva JKFD, Bento PCB

Braz J Med Biol Res · 2024 · PMID 39630808 · Full text

The objective of the present randomized trial was to verify the effect of twelve weeks of strength training with self-selected and imposed loads on muscle function, functionality, muscle quality, and perceptual and affec... The objective of the present randomized trial was to verify the effect of twelve weeks of strength training with self-selected and imposed loads on muscle function, functionality, muscle quality, and perceptual and affective responses in elderly men and women. Twenty-four volunteers were divided into two groups of 12 individuals each: self-selected group (SS) (8 women, 4 men; mean age=66.92±6.18 years) and imposed group (IMP) (8 women, 4 men; mean age=65.33±2.42 years). The strength exercise program lasted 12 weeks (3 d/w). All exercises were performed on machines. The SS group was instructed to select a weight that would allow them to complete three sets of 10 repetitions, while the IMP group had the load imposed by the researchers following the exercise prescription model recommended by American College of Sports Medicine (ACSM). Rated perceived exertion (RPE) and affective responses were recorded at the end of each session. Muscle function, functionality, and muscle quality were assessed before and after the intervention. Both groups demonstrated similar improvements in strength and functional capacity. Furthermore, the SS group reported lower RPE and higher affective responses compared to the IMP group at 8-12 weeks. In summary, the findings from this study highlighted the effectiveness of both IMP and SS intensity resistance training programs in enhancing muscle strength and functional capacity among older adults.

Machine learning approaches and genetic determinants that influence the development of type 2 diabetes mellitus: a genetic association study in Brazilian patients.

Santos KF, Assunção LP, Santos RS … +1 more , Reis AAS

Braz J Med Biol Res · 2024 · PMID 39630807 · Full text

This genetic association study including 120 patients with type 2 diabetes mellitus (T2DM) and 166 non-diabetic individuals aimed to investigate the association of polymorphisms in the genes GSTM1 and GSTT1 (gene deletio... This genetic association study including 120 patients with type 2 diabetes mellitus (T2DM) and 166 non-diabetic individuals aimed to investigate the association of polymorphisms in the genes GSTM1 and GSTT1 (gene deletion), GSTP1 (rs1695), ACE (rs4646994), ACE2 (rs2285666), VEGF-A (rs28357093), and MTHFR (rs1801133) with the development of T2DM in the population of Goiás, Brazil. Additionally, the combined effects of these polymorphisms and the possible differences between sexes in susceptibility to the disease were evaluated. Finally, machine learning models were integrated to select the main risk characteristics for the T2DM diagnosis. Risk associations were found for the GSTT1-null genotype in the non-stratified sample and females, and for mutant C allele of the VEGF-A rs28357093 polymorphism in the non-stratified sample. Furthermore, an association of heterozygous (AG) and mutant (GG) GSTP1 genotypes was observed when combined with GSTT1-null. Machine learning approaches corroborated the results found. Therefore, these results suggested that GSTT1 and GSTP1 polymorphisms may contribute to T2DM susceptibility in a Brazilian sample.

Poricoic acid A attenuates renal fibrosis by inhibiting endoplasmic reticulum stress-mediated apoptosis.

Zhao H, Liu T, Yang CE … +5 more , Hu YH, Niu Y, Lei SP, Chen L, Zhang MX

Braz J Med Biol Res · 2024 · PMID 39607209 · Full text

Renal fibrosis is a common manifestation in the progression of chronic kidney disease (CKD) to kidney failure. Currently, there is no available therapy to prevent the progression of renal fibrosis. Poricoic acid A (PAA)... Renal fibrosis is a common manifestation in the progression of chronic kidney disease (CKD) to kidney failure. Currently, there is no available therapy to prevent the progression of renal fibrosis. Poricoic acid A (PAA) isolated from Poria cocos shows notable antifibrotic effects. However, its potential mechanism is still unclear. This study aimed to evaluate the effects and the potential mechanisms of PAA against renal fibrosis. A mouse model of renal fibrosis was established using unilateral ureteral obstruction (UUO). We showed that PAA administration significantly alleviated renal lesions and collagen deposition in UUO mice. Mice with UUO resulted in epithelial-to-mesenchymal transition (EMT) and the activation of endoplasmic reticulum stress (ERS) in the renal tissues, while PAA treatment significantly inhibited EMT and ERS activation. Additionally, PAA markedly alleviated ERS-mediated apoptosis in UUO mice. Molecular docking results indicated that PAA stably combined to GRP78 and ATF4. In conclusion, these results demonstrated that PAA possesses a significant bioactivity against renal fibrosis and its treatment mechanism might be the inhibition of ERS-mediated apoptosis.

Changes in cerebral glucose metabolism among mild long COVID patients: an [18F]FDG PET/CT study.

Sakamoto JS, Lopes-Santos LE, Lacerda KJCC … +5 more , Trevisan AC, Alexandre-Santos L, Fukumori OY, Bellissimo-Rodrigues F, Wichert-Ana L

Braz J Med Biol Res · 2024 · PMID 39607208 · Full text

COVID-19, caused by SARS-CoV-2, presents diverse symptoms, including neurological manifestations. This study investigated COVID-19's neurological sequelae, focusing on the central nervous system's involvement through cer... COVID-19, caused by SARS-CoV-2, presents diverse symptoms, including neurological manifestations. This study investigated COVID-19's neurological sequelae, focusing on the central nervous system's involvement through cerebral glycolytic metabolism assessed via PET/CT. Twenty-two patients with mild long COVID cognitive symptoms and 20 healthy volunteers without cognitive, psychiatric, or neurological impairments and no history of COVID-19 infection underwent cerebral PET/CT scans using [18F]FDG to assess cerebral metabolism. The study meticulously evaluated the uptake of [18F]FDG in various brain regions, employing the CortexID Suite software for quantitative analysis. The analysis focused on identifying areas of hypometabolism and hypermetabolism, indicative of altered glucose metabolism possibly related to COVID-19's neurological impact. No statistically significant differences were found between the mild COVID and healthy groups. Although our sample was too small to generate a statistical difference between groups, future studies should explore some findings, such as hypometabolism in 15 regions and hypermetabolism in 11 regions in the mild COVID group. These changes, especially in areas linked to executive functions, sensory perception, and emotional regulation, suggest nuanced alterations in brain function. Our study did not find significant glycolytic metabolic changes in patients with mild long COVID. However, areas of glycolytic hypometabolism and hypermetabolism found in some patients showed biological plausibility with the cognitive and affective symptoms they presented. Future investigations with a larger sample size should be correlated with neuropsychological and neuropsychiatric examinations to confirm this relationship.

Exercise: a non-drug strategy of NK cell activation.

Pan H, Meng R, Jia Z … +5 more , Zhang J, Ma W, Liu Y, Wang Q, Li Q

Braz J Med Biol Res · 2024 · PMID 39607207 · Full text

Natural killer (NK) cells are a critical component of the innate immune system and one of the immune cells most sensitive to exercise. So far, it is widely believed that moderate exercise can significantly enhance the pr... Natural killer (NK) cells are a critical component of the innate immune system and one of the immune cells most sensitive to exercise. So far, it is widely believed that moderate exercise can significantly enhance the proliferation and activity of NK cells, strengthening immune function. However, the impact of exercise on NK cells is a dynamic and complex process. In addition to the type of exercise, the frequency, intensity, and duration of exercise are also key factors. This article not only briefly summarizes the activation mechanisms of NK cells but also delves into the potential importance of exercise as a non-pharmacological strategy in modulating NK cell activity and enhancing the immune system. Emerging studies have indicated that the timing and regularity of exercise bouts might also influence NK cell responses. Moreover, the interaction between exercise and other components of the immune system, such as cytokines and chemokines, could further modulate the functionality of NK cells. The above research is of crucial significance for achieving a deeper understanding of the intricate connection between exercise and NK cell function, as well as the development of effective health promotion strategies. In addition, further research is needed to investigate the effects of long-term exercise on NK cell function and the interaction between exercise and NK cell-mediated immune responses. Translating these research findings into precisely tailored exercise programs for specific populations, taking into account factors like age, health status, and genetic predisposition, could potentially offer unprecedented prospects for further advancements in this burgeoning field of study.

Optimizing genomic DNA extraction from long-term preserved formalin-fixed and paraffin-embedded lung cancer and lymph node tissues.

Faria CS, Baldavira CM, Mangone FRR … +7 more , Agati MEM, Kulikowski LD, Nagai MA, Nascimento ECTD, Mello ES, Capelozzi VL, Antonangelo L

Braz J Med Biol Res · 2024 · PMID 39607206 · Full text

Personalized therapy in lung cancer (LC) has revolutionized routine histopathology and cytopathology, emphasizing the importance of obtaining adequate material for molecular studies to support oncological decisions. Adap... Personalized therapy in lung cancer (LC) has revolutionized routine histopathology and cytopathology, emphasizing the importance of obtaining adequate material for molecular studies to support oncological decisions. Adaptations of cytologic sample preparations offer benefits for molecular testing, yet their potential remains underutilized. A significant number of LC cases is identified through specimens of aspiration or exfoliative cytology. Improving screening approaches and optimizing tissue utilization for biomarker research are crucial for effective LC management. The utilization of formalin-fixed, paraffin-embedded (FFPE) tumor tissues has become standard practice in clinical and epidemiological genetic research. However, current techniques require not only a standardized sample fixation and storage but also sufficient genetic material to yield reliable results. In this study, we utilized the Qiagen GeneRead® DNA FFPE kit with an adapted protocol for two extraction methods: one involved cutting FFPE blocks and the other involved scraping tissue from slides used for histochemical and cytological analysis. Our findings emphasized the importance of increasing the number of FFPE sections, heat deparaffinization, and adjusting proteinase K digestion time to enhance genomic DNA (gDNA) yields. Notably, scraping tissue from slides yielded superior results compared to the standard FFPE protocol. A median of 2.82 and 4.34 DNA yields for tumor and lymph node, respectively, were obtained. Our results demonstrated the feasibility of this adapted protocol for gDNA extraction in clinical and epidemiological studies. We recommend scraping tissue from slides as a reliable source of gDNA and suggest fine-tuning proteinase K digestion time and heat exposure based on the input tissue volume.

Physical exercise-mediated neuroprotective mechanisms in Parkinson's disease, Alzheimer's disease, and epilepsy.

Pinho RA, Muller AP, Marqueze LF … +2 more , Radak Z, Arida RM

Braz J Med Biol Res · 2024 · PMID 39607205 · Full text

Research suggests that physical exercise is associated with prevention and management of chronic diseases. The influence of physical exercise on brain function and metabolism and the mechanisms involved are well document... Research suggests that physical exercise is associated with prevention and management of chronic diseases. The influence of physical exercise on brain function and metabolism and the mechanisms involved are well documented in the literature. This review provides a comprehensive overview of the potential implications of physical exercise and the molecular benefits of exercise in Parkinson's disease, Alzheimer's disease, and epilepsy. Here, we present an overview of the effects of exercise on various aspects of metabolism and brain function. To this end, we conducted an extensive literature search of the PubMed, Web of Science, and Google Scholar databases to identify articles published in the past two decades. This review delves into key aspects including the modulation of neuroinflammation, neurotrophic factors, and synaptic plasticity. Moreover, we explored the potential role of exercise in advancing therapeutic strategies for these chronic diseases. In conclusion, the review highlights the importance of regular physical exercise as a complementary non-pharmacological treatment for individuals with neurological disorders such as Alzheimer's, Parkinson's disease, and epilepsy.

PMEPA1 promotes gastric cancer cell proliferation by regulating the ubiquitin-mediated degradation of 14-3-3σ and promoting cell cycle progression.

Huang H, Sun R, Xu Y … +2 more , Liu R, Chen Z

Braz J Med Biol Res · 2024 · PMID 39607204 · Full text

Gastric cancer (GC) remains a global health challenge due to its heterogeneity and diverse regional epidemiology. Treatment for advanced GC often requires chemotherapy, whose effects are closely associated with the cell... Gastric cancer (GC) remains a global health challenge due to its heterogeneity and diverse regional epidemiology. Treatment for advanced GC often requires chemotherapy, whose effects are closely associated with the cell cycle. This association highlights the critical need to understand cell cycle regulators that can influence the effectiveness of chemotherapy. Bioinformatics analyses were performed on transcriptome data from a hospital cohort and on a publicly available database. Flow cytometry was used for cell cycle analysis. The interaction of PMEPA1 with 14-3-3σ was confirmed by coimmunoprecipitation and immunofluorescence staining. Western blot analysis was performed following inhibition of protein synthesis and degradation to assess 14-3-3σ protein stability, while ubiquitination was evaluated after treatment with the proteasome inhibitor MG132. High PMEPA1 expression was detected in GC tissues and was correlated with poor prognosis. In vitro overexpression of PMEPA1 promoted GC cell proliferation, while knockdown of PMEPA1 inhibited cell proliferation and induced G2/M arrest. In vivo study showed that overexpressing PMEPA1 promoted tumor growth, while knocking down PMEPA1 inhibited tumor growth, as indicated by the level of the proliferation marker Ki67. 14-3-3σ was identified as a downstream target of PMEPA1. PMEPA1 binds to 14-3-3σ and promoted its degradation by facilitating its ubiquitination. Overexpression of PMEPA1 increased its interactions with TTC3 and 14-3-3σ, increased 14-3-3σ ubiquitination, and reduced 14-3-3σ stability, and the opposite effects were observed after PMEPA1 knockdown. PMEPA1 recruited TTC3, allowing the ubiquitination of 14-3-3σ and leading to its degradation, thus promoting cell cycle progression in GC.

Correlation between sleep duration and prevalence of hypertension: the China Health and Nutrition Survey.

Guan HS, Shangguan HJ

Braz J Med Biol Res · 2024 · PMID 39607203 · Full text

It is increasingly thought that sleep is a lifestyle factor that contributes to hypertension. However, the correlation between sleep duration and hypertension in the Chinese population remains largely unexplored. This st... It is increasingly thought that sleep is a lifestyle factor that contributes to hypertension. However, the correlation between sleep duration and hypertension in the Chinese population remains largely unexplored. This study utilized data from the 2009 China Health and Nutrition Survey to investigate the correlation between sleep duration and hypertension. Average hours of sleep per day were grouped into following categories: ≤6, 7-9, and ≥10 h. The frequency of hypertension and odds ratio (OR) were computed across different sleep duration categories. Individuals sleeping 7-9 h per day were designated as the control group. Logistic regression was utilized for multivariate analysis. Among the 9435 participants, the mean sleep duration was 7.9±1.2 h. The prevalence of hypertension was 34.1, 21.7, and 29.3% for individuals sleeping ≤6, 7-9, and ≥10 h per day, respectively. Following adjustments for age, gender, body mass index, and diabetes, a significant association was observed between prolonged (≥10 h) sleep duration and hypertension. Compared to those sleeping 7-9 h per day, the OR for hypertension was 1.21 (95%CI: 1.02-1.43, P=0.03) for individuals sleeping ≥10 h per day. This study suggested that sleeping ≥10 h per day is associated with a higher risk of hypertension in adults.

Diagnostic and prognostic value of the gasdermins in gastric cancer.

Xu Y, Chen J, Wang P … +5 more , Chen H, Zhao Y, Cao X, Wan C, Gu Y

Braz J Med Biol Res · 2024 · PMID 39607202 · Full text

Pyroptosis has attracted attention due to its role in various cancers. Recently, gasdermins (GSDMs) involved in pyroptosis have been reported to be associated with several types of cancers. However, the role of GSDMs exp... Pyroptosis has attracted attention due to its role in various cancers. Recently, gasdermins (GSDMs) involved in pyroptosis have been reported to be associated with several types of cancers. However, the role of GSDMs expression in the diagnosis and prognosis of gastric cancer (GC) is still not well understood. We analyzed the transcriptional and prognostic information and the role of GSDMs in patients with GC from TIMER, UALCAN, Human Protein Atlas (HPA), GEPIA, and Kaplan-Meier Plotter databases. The cBioPortal platform was used to discover the genetic alterations, significance, and networks of GSDMs. Furthermore, STRING, Cytoscape, and TIMER were used to explore functional enrichment and immunomodulation. GSDMB, GSDMC, GSDMD, and GSDME were more highly expressed in GC than in normal tissues in the TIMER database. Moreover, survival analyses in two databases showed that high expression of GSDME was related to shorter overall survival (OS) in patients with GC. Additionally, functional enrichment revealed that GSDMs may be involved in endopeptidase activity, peptidase regulatory activity, and cysteine peptidase activity. GSDMs correlated with infiltration levels of immune cells in GC, and GSDME correlated with the infiltrating level of CD4+ T, CD8+ T, neutrophils, macrophages, and dendritic cells. This study indicated the potential diagnostic and prognostic value of GSDMs in GC. Our results showed that GSDME could play a significant oncogenic role in GC diagnosis and prognosis. However, our bioinformatics analyses should be validated in further prospective studies.

Bioinformatic features and immunological response of recombinant antigen CTLA4-IgV-EgG1Y162 against Echinococcus granulosus.

Zhao S, Li Y, Kong H … +7 more , Zhou Y, Zhou W, Zheng J, Gong Q, Cao C, Ding J, Zhou X

Braz J Med Biol Res · 2024 · PMID 39607201 · Full text

Cystic echinococcosis (CE) is a zoonotic disease caused by the infection of Echinococcus granulosus (E. granulosus) larva. Currently, blocking the pathogenic cycle chain through immunoprophylaxis has become the main rese... Cystic echinococcosis (CE) is a zoonotic disease caused by the infection of Echinococcus granulosus (E. granulosus) larva. Currently, blocking the pathogenic cycle chain through immunoprophylaxis has become the main research direction. EgG1Y162 protein has good antigenicity and immunogenicity and is therefore a good candidate molecule for E. granulosus vaccine. Mature T cells express CTLA-4 on their surface, and its extracellular IgV region binds efficiently to the B7 molecules on antigen-presenting cells to deliver negative signals. We designed and prepared a recombinant vaccine by fusing CTLA-4IgV to the EgG1Y162 protein to exploit its binding properties. Bioinformatic methods were used to analyze the structure and epitopes of the proposed recombinant vaccine. The placement of 16 amino acids (GTDDDDKAMADIGSEF) between the CTLA-4IgV and EgG1Y162 using the skeleton structure of pET30a plasmid did not affect the correct folding of the proteins. When the recombinant proteins were co-cultured with bone marrow-induced dendritic cells (DC), the protein CTLA-4IgV-EgG1Y162 promoted its binding to DC and increased the percentage of DC maturation compared with protein EgG1Y162 in vitro and in vivo. Compared to EgG1Y162, CTLA-4IgV-EgG1Y162 promoted the proliferation of lymphocytes in spleen and the release of interferon (IFN)-γ and interleukin (IL)-4 by those lymphocytes in vitro, while it also promoted the release of protective antibodies in the serum of immunized mice in vivo. These findings indicated that the designed recombinant vaccine, CTLA-4IgV-EgG1Y162, can provide new ideas for the optimization and improvement of vaccines against E. granulosus.

Evaluation of COVID-19 cases treated in the intensive care unit in a coastal city hospital during the pandemic.

Klauss PHA, Hi EMB, Bianchi CCR … +8 more , Ruiz AU, Barros MFCB, Silva BMD, Moretto TL, Soriano FG, Curi R, Machado MCC, Gritte RB

Braz J Med Biol Res · 2024 · PMID 39504070 · Full text

SARS-CoV-2 is a novel coronavirus that infects the respiratory tract and was the causing agent of COVID-19, declared a pandemic by the World Health Organization on March 11, 2020. Several studies have been carried out to... SARS-CoV-2 is a novel coronavirus that infects the respiratory tract and was the causing agent of COVID-19, declared a pandemic by the World Health Organization on March 11, 2020. Several studies have been carried out to understand the pathophysiology of the disease, immune reactions, and risk factors that could aggravate the condition and predict the prognosis of patients. Therefore, this study aimed to evaluate the most prevalent laboratory data of hospitalized patients associated with discharge or death. A survey was conducted utilizing the medical records of COVID-19 cases in patients treated in the intensive care unit of the Guilherme Álvaro Hospital in the seaside city of Santos, Brazil. We correlated the most important variables reported in the literature to provide a global comparison of the population affected by the virus in the Santos lowlands.

Antitumor activity of membranes associated with Acmella oleracea extract.

Priante-Silva CA, Godoi BH, Menegon RF … +2 more , Silva NSD, Pacheco-Soares C

Braz J Med Biol Res · 2024 · PMID 39504069 · Full text

Epithelial cancers, such as epidermoid cancer and some adenocarcinomas, affect surface areas that are generally more accessible to various treatments. However, this group of tumor cells has an aggressive behavior, leadin... Epithelial cancers, such as epidermoid cancer and some adenocarcinomas, affect surface areas that are generally more accessible to various treatments. However, this group of tumor cells has an aggressive behavior, leading to a high annual mortality rate. The development of a biomaterial that is non-invasive, can kill tumor cells, and prevent opportunistic infections is the basis for the treatment for this type of cancer. Therefore, the objective of this study was to develop a biomaterial from chitosan and A. oleracea extracts that exhibits cytotoxic action against the HEp-2 tumor cell line. Dried crude 90% ethanol extracts were obtained through ultrasound-assisted maceration, followed by liquid-liquid extraction to yield the butanol fraction. From these extracts, chitosan membranes were developed and evaluated for their antitumor activity against HEp-2 using viability tests with crystal violet and MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay, in addition to a wound healing test. The cytotoxic assays indicated a significant reduction in cell density and mitochondrial activity, especially at the concentration of 1000 µg/mL of crude extract. The butanol fraction had minimal effects on mitochondrial activity. The wound healing test demonstrated that the biomaterial and extract prevented closure of the wound created in the cell monolayer within 48 h of incubation and caused changes in cell morphology. In view of this, we concluded that a chitosan membrane associated with a 90% ethanol extract of Acmella oleracea exhibited cytotoxic activity is a potential alternative treatment for superficial cancers.

Therapeutic effects of whole-body vibration on postmenopausal women with osteoporosis: a systematic review and meta-analysis.

Li Q, Liang L, Gao C … +1 more , Zong B

Braz J Med Biol Res · 2024 · PMID 39504068 · Full text

The objective of this study was to assess the efficacy of whole-body vibration (WBV) on bone mineral density (BMD), pain levels, and body composition in postmenopausal women with osteoporosis (PMOP). Relevant studies wer... The objective of this study was to assess the efficacy of whole-body vibration (WBV) on bone mineral density (BMD), pain levels, and body composition in postmenopausal women with osteoporosis (PMOP). Relevant studies were retrieved from the PubMed, EMBASE, Web of science, CENTRAL, and PEDro databases. Thirteen randomized controlled trials with 783 patients were enrolled. The meta-analysis results showed that WBV can significantly increase lumbar spine BMD (WMD=0.018; 95%CI: 0.004 to 0.032; P=0.011), femoral neck BMD (WMD=0.005, 95%CI: 0.001 to 0.011, P=0.0493), and reduce pain degree (WMD=-0.786; 95%CI: -1.300 to -0.272; P=0.0027) in PMOP, but has no significant effect on patients' muscle mass (WMD=0.547; 95%CI: -1.104 to 2.199; P=0.5158) as well as fat mass (WMD=0.530; 95%CI: -2.389 to 3.448; P=0.7222). To conclude, WBV showed the potential to provide positive benefits in improving BMD and relieving pain of PMOP.

Esculetin attenuates cerebral ischemia-reperfusion injury and protects neurons through Nrf2 activation in rats.

Zhang Z, Zhang J, Shi R … +3 more , Xu T, Wang S, Tian J

Braz J Med Biol Res · 2024 · PMID 39504067 · Full text

Nuclear factor erythroid 2 (NF-E2)-related factor 2 (Nrf2) is a key transcription factor in the antioxidant response and is associated with various chronic diseases. The aim of this study was to explore the action of esc... Nuclear factor erythroid 2 (NF-E2)-related factor 2 (Nrf2) is a key transcription factor in the antioxidant response and is associated with various chronic diseases. The aim of this study was to explore the action of esculetin, a natural dihydroxy coumarin, on attenuating middle cerebral artery occlusion (MCAO) and reperfusion, and whether its effect is dependent on Nrf2 activation, as well as nuclear factor-kappa B (NF-κB) inhibition. Two doses of esculetin (20 and 40 mg/kg) were tested on rats with MCAO reperfusion. Neurological deficiency, oxidative stress, and pathological analyses were performed to evaluate its effect. An in vitro analysis was also used to confirm whether its action was dependent on the Nrf2/HO-1/NQO-1 pathway. Compared with MCAO reperfusion rats, esculetin improved infarct volume and increased normal-shaped neuron cells by decreasing tumor necrosis factor-alpha (TNF-α), interleukin (IL)-6, and IL-1β levels. The oxidative stress parameter malondialdehyde (MDA) decreased and the activity of superoxide dismutase (SOD) and glutathione/glutathione disulfide (GSH/GSSG) ratio increased after esculetin treatment. Moreover, esculetin inhibited NF-κB activation induced by MCAO. In vitro, hypoxia/reoxygenation (H/R) impaired the viability of rat neuron cells and esculetin showed a neuron protection effect on cells. Nrf2 inhibitor Brusatol inhibited the activation of Nrf2, heme oxygenase-1 (HO-1), and NAD(P)H quinone oxidoreductase 1 (NQO-1) caused by esculetin and abolished its protection effect. Esculetin protected cerebral neurons from ischemia-reperfusion injury by inhibiting NF-κB and Nrf2/HO-1/NQO-1 activation.

MRTO4 acts as an independent prognostic and immunological biomarker and is correlated with tumor microenvironment in hepatocellular carcinoma.

Liang B, Li L, He C … +2 more , Wang M, Mao G

Braz J Med Biol Res · 2024 · PMID 39504066 · Full text

Liver cancer is a malignant tumor found worldwide. mRNA turnover 4 homolog (MRTO4) is highly expressed in hepatocellular carcinoma (HCC) tissues, and we explored its relationship with HCC. All cancer data were downloaded... Liver cancer is a malignant tumor found worldwide. mRNA turnover 4 homolog (MRTO4) is highly expressed in hepatocellular carcinoma (HCC) tissues, and we explored its relationship with HCC. All cancer data were downloaded from the Cancer Genome Atlas (TCGA), the Cancer Immune Atlas (TCIA), and the Human Protein Atlas (THPA). Stromal scores, immune scores, and ESTIMATE scores were calculated by "ESTIMATE" R package. Single sample gene set enrichment analysis and CIBERSORT were used to evaluate the immune status and infiltration of cancer tissues. pRRophetic R package was used to predict the half-maximal inhibitory concentration (IC50) of different drugs in each sample. MRTO4 overexpression was associated with poor prognosis in HCC, and positively correlated with the stage and grade of HCC patients. The average immunophenoscore (IPS) of the low MRTO4 group was significantly higher than that of the high MRTO4 group. Tumor microenvironment (TME) scores were significantly higher in the low MRTO4 group than in the high MRTO4 group in HCC. MRTO4 expression was positively correlated with tumor mutation burden (TMB) and was positively correlated with most immune checkpoint gene expressions in HCC. Drug sensitivity analysis showed significantly higher IC50 values for 5-fluorouracil, gemcitabine, and sorafenib in patients with low MRTO4 expression than in those with high MRTO4 expression. MRTO4 acts as an independent prognostic and immunological biomarker and is correlated with clinical stage, tumor grade, and drug sensitivity in HCC. It may serve as a putative therapeutic target and potential biomarker for prognosis of HCC.

Association of Hibiscus sabdariffa and high-intensity interval training induces reduction in adiposity and beneficial metabolic adaptations in obesity without changes in lipid metabolism.

Oliveira DBO, Giordani MA, Luvizotto RAM … +6 more , Nascimento AFD, Santos MCD, Santos KCC, Lima-Leopoldo AP, Leopoldo AS, Sugizaki MM

Braz J Med Biol Res · 2024 · PMID 39504065 · Full text

High-intensity interval training (HIIT) has stood out as a treatment for obesity, leading to adaptations of the cardiovascular system and reducing body adiposity. In addition, the search for alternative therapies for wei... High-intensity interval training (HIIT) has stood out as a treatment for obesity, leading to adaptations of the cardiovascular system and reducing body adiposity. In addition, the search for alternative therapies for weight loss has intensified. The administration of Hibiscus sabdariffa (Hs) has been described as an efficient supplement in weight loss and in the treatment of metabolic changes associated with obesity. In this context, the objective was to investigate the effects of the association of Hs and HIIT on metabolic adaptations and lipid metabolism in obese rats. Wistars rats were subjected to obesity and subsequently randomized into 4 groups: obese (Ob), obese + HS (ObHs), obese + HIIT (ObHIIT), and obese + HS + HIIT (ObHsHIIT). For 8 weeks, ObHs and ObHsHIIT rats received Hs extract daily (150 mg/kg of body weight) and trained groups (ObHIIT and ObHsHIIT) were subjected to a HIIT program on a treadmill. Nutritional profile, glycemic curve, biochemical profile, and liver glycogen were determined. HIIT decreased caloric intake, feed efficiency, body adiposity, total body fat, and body weight gain, associated with improvements in physical performance parameters and a smaller glycemic curve and area. Hs had a hepatoprotective effect, reducing alkaline phosphatase values, but its effects were more pronounced when associated with HIIT. Therefore, the combination of treatments promoted a reduction in food consumption and body adiposity, as well as an improvement in physical performance and glycemic profile, but without changes in lipid metabolism.
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