Braz. J. Med. Biol. Res. [JOURNAL]
Sun
200 papers
The utility of an artificial intelligence model based on decision tree and evolution algorithm to evaluate steatotic liver disease in a primary care setting.
Goulart AC, Alencar AP, Tunes G … +11 more , Bianchi LLT, Miname MH, Padilha CM, Pescuma JMS, Rodrigues ALCC, Henares BB, Almeida MS, Machado TAO, Syllos DH, Wang YP, Rienzo M
Braz J Med Biol Res · 2025 · PMID 40531757 · Full text
Many ways of classifying steatotic liver disease (SLD) with metabolic conditions have been proposed. Thus, SLD-related variables were verified using a decision tree. We tested if the suggested components of the actual cl...
Many ways of classifying steatotic liver disease (SLD) with metabolic conditions have been proposed. Thus, SLD-related variables were verified using a decision tree. We tested if the suggested components of the actual classification (metabolic dysfunction-associated steatotic liver disease, MASLD) are also present in young and middle-aged adults. In a cross-sectional study involving 6,839 adults (median age: 46 years, 69.5% men) in a primary care setting, a decision tree was created to determine potential clinical and laboratory variables related to SLD. The odds ratio (OR) with a respective 95% confidence interval (95%CI) was calculated for both sexes. SLD frequency was 26.6% (23% in men). More variables and with higher ORs for the association with SLD were identified in women: category 1 (body mass index (BMI) ≥29 kg/m2, age <51 years, high-sensitivity C-reactive protein (hs-CRP) ≥0.195 mg/dL): OR=10.9, 95%CI: 4.40-26.6; category 2 (BMI <9 kg/m2, metabolic syndrome (MS), age ≥50 years, neck circumference (NC) ≥36 cm): OR=8.1, 95%CI: 2.2-29.9; and category 3 (BMI ≥29 kg/m2, age <51 y-old, dyslipidemia, high-density lipoprotein cholesterol (HDL-c) <42 mg/dL): OR=4.7, 95%CI: 2.20-10.7. For men: category 1 (waist circumference (WC) ≥101 cm, alanine aminotransferase (ALT) <28 mg/dL, glycated hemoglobin (HbA1c) ≥5.7%): OR=4.7, 95%CI: 2.8-7.9; and category 2 (WC ≥101 cm, ALT ≥28 mg/dL): OR=3.2, 95%CI: 2.5-4.0). The decision tree identified more variables related to SLD, particularly in women, such as age of more than 50 years, elevated hs-CRP, and NC≥36 cm than variables related to MASLD.
Effect of high-intensity childhood games on heart rate variability, saliva leptin concentrations, and body composition in children.
Rodriguez-Triviño CY, Quintana S, Osorio-Vélez CE … +1 more , Garcia-Florez M
Braz J Med Biol Res · 2025 · PMID 40531756 · Full text
The aim of this study was to evaluate the effect of high-intensity childhood games on cardiac autonomic regulation, obesity biomarkers, and body composition in overweight or obese children compared to moderate-intensity...
The aim of this study was to evaluate the effect of high-intensity childhood games on cardiac autonomic regulation, obesity biomarkers, and body composition in overweight or obese children compared to moderate-intensity games. A single-blind, randomized controlled study was conducted including children aged 6 to 9 years with overweight or obesity. Participants were randomly assigned to two groups: 33 in the moderate-intensity interval game group (MIIG) and 29 in the high-intensity interval game group (HIIG). The intervention lasted 16 weeks, with measurements conducted under double blinding. The study followed institutional ethical standards and was registered on ClinicalTrials.gov (CT NCT05294601). A total of 74 children were recruited, with 7 excluded after sports medicine assessment, leaving 67 children randomized. Five participants dropped out during the study. HRV analysis revealed significant differences in frequency dominance in the HIIG group. High-frequency power, linked to parasympathetic dominance, increased from 59.3 to 65.8 nu (P=0.03), while low-frequency power, related to sympathetic activity, decreased from 40.6 to 34.13 nu (P=0.04). Salivary leptin concentrations decreased significantly from 0.33 to 0.32 ng/mL (P=0.008) in the MIIG group and from 0.35 to 0.32 ng/mL (P=0.004) in the HIIG group. Childhood games positively impacted anthropometry, HRV, and leptin concentrations in both intensity groups, indicating metabolic improvement. However, only the high-intensity strategy enhanced parasympathetic dominance and sympathetic-parasympathetic balance, potentially reducing long-term cardiovascular risk.
Stress-stimulated epinephrine induces premature senescence in dermal fibroblasts and contributes to impaired skin wound healing.
Silva JTD, Meira COS, Nogueira JS … +2 more , Lanzetti M, Romana-Souza B
Braz J Med Biol Res · 2025 · PMID 40531755 · Full text
External factors accelerate cellular senescence in the skin and compromise its repair process. Psychological stress impairs skin wound healing, but no study examined its role in cellular senescence during skin tissue rep...
External factors accelerate cellular senescence in the skin and compromise its repair process. Psychological stress impairs skin wound healing, but no study examined its role in cellular senescence during skin tissue repair. Thus, this study evaluated the effect of stress on cellular senescence during skin wound healing. Human dermal fibroblasts (HDFs) and human skin from aged and young donors were treated with a non-lethal dose of epinephrine or hydrogen peroxide following a stress-induced premature senescence protocol. In vitro, epinephrine or hydrogen peroxide promoted the expression of senescence-associated β-galactosidase, p53, and notch target gene hairy and enhancer of split 1 (HES1) in HDFs, confirming the induction of premature senescence. A higher expression of matrix metalloproteinase-9 and interleukin-8 was observed in HDFs incubated with epinephrine or hydrogen peroxide, confirming a pro-inflammatory senescence-associated secretory phenotype. The protein levels of silent information regulator sirtuin 1, which is associated with a longer lifespan, were not changed in HDFs submitted to stressful conditions. In ex vivo experiments, epinephrine administration impaired wound closure and increased HES1 expression in aged human skin. In conclusion, stress-induced high epinephrine level induced premature senescence in HDFs, which contributes to impaired wound healing in young and aged skin.
Nanoparticle tools for maximizing oral drug delivery.
Cahyani DM, Mubarok AS, Hariawan BS … +7 more , Amalina I, Drake P, Parumasivam T, Sahu RK, Rijal MAS, Sari R, Miatmoko A
Braz J Med Biol Res · 2025 · PMID 40531754 · Full text
The biological permeability and water solubility of drugs can pose substantial obstacles to oral drug delivery, the most common mode of drug administration for improving human health. Solubility determines the amount of...
The biological permeability and water solubility of drugs can pose substantial obstacles to oral drug delivery, the most common mode of drug administration for improving human health. Solubility determines the amount of drug that can be dissolved in solution, whereas permeability is the ability to permeate across biological membranes, determining therapeutic efficacy and safety. Some biological barriers, such as gastrointestinal pH, enzymes, and mucus, may affect the dissolution or absorption of therapeutic drugs. Physical or chemical approaches can be used to modify the water solubility or enhance the permeability. Moreover, nanocarriers, which can increase drug stability through encapsulation, enhance absorption due to their extensive surface area, and facilitate the targeted administration of medications to certain areas, could be useful for drug delivery systems. Nanoparticles can increase drug solubility by particle size reduction, complexation, and drug encapsulation and increase permeation by retention in tumors, opening of tight junctions, membrane fluidization, or intestinal mucoadhesion. Despite the many advantages of nanoparticle drug formulations, they also have several limitations, such as complicated manufacturing processes, nanotoxicity, and stability issues. In this article, we provide a comprehensive description of nanoparticle tools for maximizing oral drug delivery.
Protective effects of Aloe vera extract against doxorubicin-induced degeneration in ovarian follicles and stromal cells in mice.
Assis EIT, Godinho AN, Freire JMO … +8 more , Lima Neto MF, Costa JJN, Souza ALP, Monte APOD, Matos MHT, Sousa ALM, Silva JRV, Silva AWB
Braz J Med Biol Res · 2025 · PMID 40531753 · Full text
The present study aimed to evaluate the protective effects of Aloe vera on doxorubicin (DOX)-induced degeneration in ovarian follicles and stromal cells in mice. Mice (n=48) were randomly divided into six groups. The pos...
The present study aimed to evaluate the protective effects of Aloe vera on doxorubicin (DOX)-induced degeneration in ovarian follicles and stromal cells in mice. Mice (n=48) were randomly divided into six groups. The positive control group mice received pretreatment of N-acetylcysteine orally (po), followed by a single intraperitoneal (ip) dose of DOX after 1 h (NAC+DOX). The negative control group mice were pre-treated with saline (po) and administered a single DOX dose (ip) after 1 h (SAL+DOX). The other groups of mice were pre-treated with different concentrations (0.1, 1.0, or 10.0 mg/kg; po) of Aloe vera and then received a single dose of DOX (ip) after 1 h (AV0.1+DOX, AV1.0+DOX, and AV10.0+DOX). The control group received saline po and ip (SAL+SAL). Aloe vera was administered once daily for 3 consecutive days. On the fourth day, the ovaries were processed for histological analysis, immunohistochemistry, and real-time PCR (mRNA for superoxide dismutase (SOD), catalase (CAT), nuclear factor erythroid 2-related factor 2 (NRF2), and tumor necrosis factor-α (TNF-α). Results showed that 0.1 and 1.0 mg/kg Aloe vera protected ovarian follicles and stromal density against DOX-induced degeneration. Furthermore, 0.1 and 1.0 mg/kg Aloe vera reduced TNF-α protein expression and increased NRF2, SOD, and CAT mRNA levels. In conclusion, 0.1 and 1.0 mg/kg Aloe vera had protective effects against DOX-induced degeneration in ovarian follicles and stromal cells in mice.
Microencapsulation of fish oil by spray-drying using two different wall materials: a comparison.
Pinto SCB, Kluczkovski AM, Lemos HB … +3 more , Torres VG, Jesus AVB, Souza TP
Braz J Med Biol Res · 2025 · PMID 40531752 · Full text
Oils and fats have a wide range of health benefits, especially those that have a high concentration of polyunsaturated fatty acids, like fish oils. Unfortunately, oils are highly susceptible to heat, light, and oxygen de...
Oils and fats have a wide range of health benefits, especially those that have a high concentration of polyunsaturated fatty acids, like fish oils. Unfortunately, oils are highly susceptible to heat, light, and oxygen degradation, causing them to lose the qualities that would make them interesting for the public. With this in mind, this study compared two methods of spray-drying, a technique that helps preserve the stability of oils in storage for longer periods of time. Emulsions made with skimmed milk powder and with maltodextrin and whey protein hydrolysate were spray-dried, resulting in 2 different microencapsulated fish oils. They were compared regarding encapsulation efficiency, water activity, moisture content, and peroxide index. The skimmed milk showed better results, with a 28.17% lower peroxide index than the non-encapsulated oil and lower water activity and moisture content compared to the emulsion using maltodextrin (2.690±0.19% vs 6.747±0.29% moisture content and 0.376±0.013 vs 0.554±0.006 water activity). Since skimmed milk powder is rather cheap, it is ideal for spray-drying, a simple and fast technique. In this way, fish oil can be safely microencapsulated in powder form, lasting longer than the oil capsules currently available, since the oil is protected from light, temperature, moisture, and oxidation. In addition, the oily odor is masked, making it more appealing to the consumer, and it may be combined with other powders, like vitamins and minerals, which opens up new possibilities for the production of supplements.
Montelukast reduced docetaxel-induced peripheral neuropathy in rats by altering oxidative stress, histopathological damage, and gene expressions.
Karakoç MD, Özmen Ö, Zengin MN … +1 more , Çiftçi O
Braz J Med Biol Res · 2025 · PMID 40465884 · Full text
Peripheral neuropathy (PN) is a common side effect of docetaxel (DTX). In this study, we aimed to evaluate the effects of montelukast (MNT), a leukotriene receptor antagonist drug, against DTX-induced PN in rats. Thirty-...
Peripheral neuropathy (PN) is a common side effect of docetaxel (DTX). In this study, we aimed to evaluate the effects of montelukast (MNT), a leukotriene receptor antagonist drug, against DTX-induced PN in rats. Thirty-two male rats were divided into four groups and treated for four weeks: control (sham), DTX (5 mg/kg per week, ip), MNT (10 mg/kg per day, po), and DTX+MNT (5 mg/kg per week, ip + 10 mg/kg per day, po). Behavioral tests (hot plate, tail flick, and rotarod) were conducted. Histopathological, molecular (RT-PCR), and biochemical (ELISA) analyses were performed on sciatic nerve, liver, and serum samples. MNT reduced the malondialdehyde (MDA) levels and increased the superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH) parameters in sciatic nerve tissues. Unlike DTX, MNT resulted in increased Bcl-2 gene expression and decreased caspase-3 (Cas-3) and Bax expressions. DTX caused sensory and motor neuropathy, as revealed by the hot plate, tail flick, and rotarod tests. The co-administration of MNT significantly mitigated the sensory and motor neuropathy induced by DTX. MNT improved the levels of NCAM, p38α MAPK, and nuclear factor kappa B (NF-κB), which were impaired in the sciatic nerve tissues due to DTX administration. Additionally, it reduced the levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), which had increased due to DTX. Histopathological examination revealed that DTX-related sciatic nerve damage was mitigated by MNT administration. The results indicated that MNT may have a protective effect against DTX-induced PN in rats.
Low-intensity sciatic nerve-stretch injury increases nociception, anxiety-like behaviors, and astrocyte activity in male Wistar rats.
Silva-Cardoso GK, Bello-Junior PE, Lazarini-Lopes W … +2 more , Ferrarese-Tiballi AA, Leite-Panissi CRA
Braz J Med Biol Res · 2025 · PMID 40465883 · Full text
The incidence of chronic pain in the general population is highly correlated to anxiety disorders, which promote negative effects on the quality of life. Stretch injury is the primary cause of nerve dysfunction and injur...
The incidence of chronic pain in the general population is highly correlated to anxiety disorders, which promote negative effects on the quality of life. Stretch injury is the primary cause of nerve dysfunction and injury in the civilian population. Here, we characterized changes in nociception, anxiogenic-like behaviors, and astrocyte expression in the low-intensity sciatic nerve-stretch injury (NSI) model. Male Wistar rats were submitted to NSI, chronic constriction injury of the sciatic nerve (CCI), or sham surgery (SHAM). Animals were submitted to nociceptive tests (von Frey, acetone, and hot plate) before surgery and 6, 12, 18, and 24 days post-surgery. Anxiety-like behaviors were assessed in the open field test (OFT) 23 days after surgery. Immunofluorescence for astrocyte activity (glial fibrillary acidic protein (GFAP)) was performed in cortical, thalamic, and brainstem areas involved with pain and emotional processing. Animals submitted to NSI showed increased mechanical allodynia and thermal hyperalgesia, similar to those submitted to CCI. In the OFT, both NSI and CCI animals showed an increase in anxiety-like behaviors. Also, NSI animals presented an increased expression of GFAP in all analyzed areas, similar to CCI animals. In conclusion, the NSI model produced behavioral alterations comparable to those observed in the CCI model, including hypersensitivity to mechanical and thermal (heat) stimuli that lasted for more than three weeks. Additionally, both models induced a similar increase in GFAP expression in cortical, thalamic, and brainstem regions.
Prevalence and factors associated with the presence of oral infections in pregnant women in a medium-sized municipality in Brazil.
Godoi APN, Bernardes GCS, Godoi LN … +3 more , Nogueira LS, Rocha GM, Barros-Pinheiro M
Braz J Med Biol Res · 2025 · PMID 40465882 · Full text
The objective of this study was to estimate the prevalence and factors associated with oral changes, including infections and other oral conditions in pregnant women who underwent prenatal care in public health units in...
The objective of this study was to estimate the prevalence and factors associated with oral changes, including infections and other oral conditions in pregnant women who underwent prenatal care in public health units in the city of Divinópolis, Minas Gerais. This was a cross-sectional study carried out with baseline data from a cohort of 588 pregnant women (aged 14 to 43 years) from 2019 to 2023. Data were collected through interviews and oral clinical examination, using a structured questionnaire. The event of interest was the presence of oral infection. The absolute and relative frequencies of the variables were calculated. Logistic regression was used to evaluate the association between the explanatory variables and the presence of oral infection, with estimation of odds ratios and 95% confidence intervals. Among the participants, 47.8% had oral infections. In the multivariate analysis, the variables that showed a significant association with oral infection were: lower education, last visit to the dentist more than 6 months ago, lower frequency of flossing, regular intake of alcoholic beverages, and self-report of poor oral health. This study highlighted sociodemographic and behavioral disparities and the importance of prenatal dental care. Insights for adapting interventions were provided, although further studies are needed.
The body weight-walking distance product as a superior parameter in determining the VO2 on-kinetics in coronary artery disease.
Rocco IS, Gomes WJ, Viceconte M … +7 more , Matos-Garcia BC, Menezes-Rodrigues FS, Tallo FS, Arida RM, Hossne Junior NA, Arena R, Guizilini S
Braz J Med Biol Res · 2025 · PMID 40465881 · Full text
The 6-minute walk test is frequently used to assess the functional capacity of the cardiac disease population. Nevertheless, anthropometric differences can confound or misestimate performance, which highlights the need f...
The 6-minute walk test is frequently used to assess the functional capacity of the cardiac disease population. Nevertheless, anthropometric differences can confound or misestimate performance, which highlights the need for new parameters. This study aimed to investigate the potential of the body weight-walking distance product (D·W) compared to the 6-minute walk test distance to predict exercise capacity measured by oxygen uptake (VO2) on-kinetics in coronary artery disease (CAD) patients. A cross-sectional study was conducted in a tertiary-care reference institution. Forty-six participants with multivessel CAD with and without left ventricular dysfunction underwent a 6-minute walk test with simultaneous use of mobile telemetric cardiopulmonary monitoring to evaluate VO2 kinetics and other cardiorespiratory responses. The Borg rating of perceived exertion for lower limb discomfort was only correlated with the D·W (P=0.007). The percent predicted and actual distance were only modestly to moderately correlated with VO2 on-kinetics (R2=0.12 and R2=0.29, P<0.05). All the associations of VO2 on-kinetics parameters were improved, showing a stronger correlation to the D·W (R2=0.49, P<0.0001), which also had a larger effect size to identify differences between coronary disease patients compared to distance walked (d=1.32 vs d=0.84). The D·W demonstrated potential to be better than the distance walked in determining VO2 on-kinetics in participants with CAD with and without left ventricular dysfunction.
Changes in microRNA expression associated with preeclampsia: a systematic review.
Lopes ACS, Macedo AA, Mendes FS … +3 more , Costa IM, Dusse LMS, Alpoim PN
Braz J Med Biol Res · 2025 · PMID 40465880 · Full text
Preeclampsia (PE) is a disease of pregnancy characterized by the new onset of hypertension accompanied by proteinuria and/or other signs of maternal organ dysfunction that manifests after 20 weeks of gestation. MicroRNAs...
Preeclampsia (PE) is a disease of pregnancy characterized by the new onset of hypertension accompanied by proteinuria and/or other signs of maternal organ dysfunction that manifests after 20 weeks of gestation. MicroRNAs (miRNAs) are small non-coding RNAs (19-25 nucleotides) that function in the post-transcriptional regulation of gene expression. Many studies have suggested that different microRNA expression profiles may be associated with the development of PE. Hence, this study aims to report differentially expressed microRNAs that may be associated with the pathogenesis of PE and investigate whether different miRNA expression profiles are associated with different PE classifications and different phases of pregnancy. The bibliographic search was conducted from September 2021 to August 2024 and was performed on MEDLINE/PubMed, EMBASE, and Web of Science. This systematic review followed the methodological guidelines of the Cochrane Collaboration Manual for Systematic Intervention Reviews and was written according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Of the 1362 studies identified, 263 articles were selected as the sample of this study. The most frequently cited upregulated microRNAs were: miR-210, miR-155, miR-518b, miR-181a, miR-125b, miR-183, and miR-16. The most frequently cited downregulated microRNAs were: miR-363, miR-18a, miR-144, miR-149, miR-16, miR-18b, and miR-195. This study will serve as a reference to guide future experimental research. In addition, knowledge of the expression profiles of microRNAs associated with PE can help in the development of new protocols for early prediction of the disease.
Biological responses to biomaterials: a review.
Gomes YVR, Tavares AA, Barbosa RC … +5 more , Tomaz AF, Sousa WJB, Oliveira LCC, Silva SML, Fook MVL
Braz J Med Biol Res · 2025 · PMID 40367018 · Full text
Biomaterials stimulate diverse biological responses, including inflammation, wound healing, foreign body reactions, and fibrous encapsulation, all critical for evaluating biocompatibility and effectiveness. These respons...
Biomaterials stimulate diverse biological responses, including inflammation, wound healing, foreign body reactions, and fibrous encapsulation, all critical for evaluating biocompatibility and effectiveness. These responses are influenced by the material's physicochemical and biological properties, such as composition, texture, and surface characteristics. Adverse reactions, such as severe inflammation or fibrous encapsulation, can hinder tissue integration, jeopardizing patient health and increasing healthcare costs. This review aimed to summarize the current scientific evidence on biological responses to biomaterials. A systematic search was conducted through multiple databases (VHL, PubMed, SCOPUS, EMBASE, and Web of Science) including in vitro and in vivo studies that compared biomaterial interactions with the natural immune response (innate and adaptive). From the 791 articles identified, 25 met strict inclusion criteria. These studies revealed variations in immune responses and material surface characteristics, highlighting advancements made to enhance tissue integration. Bioactive materials demonstrated greater potential for tissue regeneration, while inert materials triggered moderate inflammatory reactions. This variability emphasizes the need for a personalized biomaterial selection, considering both short-term biocompatibility and long-term tissue functionality. This review underscores the importance of comprehensive evaluation to optimize biomaterial performance in clinical applications.
Effects of COVID-19 on the contrast sensitivity.
Silva GM, Souto JJS, Fernandes T … +3 more , Souza GS, Andrade MJO, Santos NAD
Braz J Med Biol Res · 2025 · PMID 40367017 · Full text
There are significant gaps in understanding the extent of the damage caused by COVID-19, with few publications examining its link to contrast sensitivity function (CSF). The aim of the present study was to evaluate CSF a...
There are significant gaps in understanding the extent of the damage caused by COVID-19, with few publications examining its link to contrast sensitivity function (CSF). The aim of the present study was to evaluate CSF at low, medium, and high spatial frequencies in individuals with and without a history of COVID-19. Thirty adults, both male and female, aged between 18 and 49 years, participated in the study, 15 with a history of COVID-19 and 15 without. CSF was measured using Metropsis software (version 11) and vertical sine-wave gratings with spatial frequencies ranging from 0.2 to 19.8 cycles per degree (cpd). The results indicated COVID-19-related changes in CSF at spatial frequencies of 6.1 (U=36.00; P=0.003; r=-0.55), 13.2 (U=29.00; P=0.001; r=-0.61), 15.9 (U=17.00; P=0.001; r=-0.70), and 19.8 cpd (U=13.00; P=0.001; r=-0.73). The observed decrease in CSF within specific spatial frequency bands suggested that the visual system of individuals exposed to COVID-19 required higher contrast levels to detect high spatial frequencies. This psychophysical finding indicated that COVID-19 altered the functioning of the visual system and likely affected the neural mechanisms responsible for processing high spatial frequencies.
ESR1 overexpression is a biomarker of relapse and worse prognosis in stage I endometrioid endometrial carcinoma.
Chaves CBP, Nicolau-Neto P, Simão TA … +7 more , Souza-Santos PT, Bergmann A, Brewer L, Moreira FCB, Reis BSB, Moreira MAM, Pinto LFR
Braz J Med Biol Res · 2025 · PMID 40367016 · Full text
Endometrial cancer (EC) is the most common pelvic gynecologic malignancy in developed countries, and its incidence is also increasing in developing countries. Endometrioid endometrial carcinoma (EEC) is the most frequent...
Endometrial cancer (EC) is the most common pelvic gynecologic malignancy in developed countries, and its incidence is also increasing in developing countries. Endometrioid endometrial carcinoma (EEC) is the most frequent subtype. EEC is often associated with favorable clinicopathological features and a good prognosis, especially when diagnosed in stage I. Although some patients have no signs to predict locally advanced or metastatic disease, they may present tumor relapse in the future. There is no biomarker capable of predicting the relapse of stage I EEC. The present study applied a transcriptome analysis to identify differentially expressed genes in stage I EEC, comparing relapsed with non-relapsed tumors. The estrogen receptor 1 gene (ESR1) was overexpressed in EEC stage I samples from patients who developed relapse by 4.3-fold compared to non-relapsed tumors. Subsequently, an independent set of 64 stage I EEC samples was used to validate ESR1 gene overexpression in relapsed tumors and assess estrogen receptor alpha (ERα) protein levels. ESR1 was confirmed to be overexpressed in samples from relapsed tumors, and its expression level was an independent prognostic variable for disease-free (hazard ratio=7.25) and overall survival (hazard ratio=5.15). In contrast, Erα did not show different values between relapsed and non-relapsed tumors. We concluded that ESR1 overexpression is a biomarker for poor prognosis in stage I EEC.
Neuromuscular fatigue in men and women during severe-intensity exercise.
Cristina-Souza G, Schamne JC, Souza-Santos P … +5 more , Santos-Mariano AC, Coelho DB, Bertuzzi R, Lima-Silva AE, Marinho AH
Braz J Med Biol Res · 2025 · PMID 40367015 · Full text
The aim of this study was to explore sex differences in neuromuscular fatigue during a severe-intensity cycling exercise. Twenty-four healthy participants (12 women and 12 men) cycled at 80% of the difference between gas...
The aim of this study was to explore sex differences in neuromuscular fatigue during a severe-intensity cycling exercise. Twenty-four healthy participants (12 women and 12 men) cycled at 80% of the difference between gas exchange threshold and maximal power output to the limit of tolerance. Neuromuscular fatigue was assessed by the decrease in maximal voluntary contraction of the knee extensors before and after exercise, and central and peripheral fatigue was measured by the decrease in voluntary activation and quadriceps potentiated twitch force before and after exercise. Women presented shorter time to task failure (P=0.025) and lower levels of neuromuscular fatigue (P=0.006) and peripheral fatigue (P<0.001) than men. Women and men showed different patterns of muscle activation during exercise, with women presenting greater muscle activation at the beginning of exercise and sustaining this elevated muscle activation throughout exercise, while men increased muscle activation from the beginning to the end of exercise. In conclusion, women had lower levels of neuromuscular fatigue, mainly caused by lower levels of peripheral fatigue, and a different muscle activation pattern in an exhaustive severe-intensity cycling exercise.
Overexpression of SERPINA3 inhibits castration-resistant prostate cancer progression by enhancing M1 macrophage recruitment via CXCL2 upregulation.
Xie J, Chen Q, Li L … +1 more , Liu J
Braz J Med Biol Res · 2025 · PMID 40367014 · Full text
The primary objective of the present study was to identify differentially expressed genes (DEGs) associated with castration-resistant prostate cancer (CRPC) to verify the potential mechanism of CRPC progression. DEGs fro...
The primary objective of the present study was to identify differentially expressed genes (DEGs) associated with castration-resistant prostate cancer (CRPC) to verify the potential mechanism of CRPC progression. DEGs from CRPC datasets were filtered with a P<0.05 and Spearman correlation coefficient ≥0.3. Serpin peptidase inhibitor, clade A member 3 (SERPINA3), was uniquely present in three CRPC datasets, and its low expression in CRPC was confirmed in cell lines and tissues. Colony formation, transwell assays, and subcutaneous tumor formation experiments in mice demonstrated that overexpression of SERPINA3 may significantly inhibit the proliferation and invasion of PC3 cells. Mechanistic studies revealed that, in prostate cancer (PCa), SERPINA3 can activate the interleukin (IL)-17 and tumor necrosis factor (TNF)α signaling pathways by promoting the expression of CXC chemokine ligand 2 (CXCL2), thereby increasing the recruitment of M1 macrophages into the tumor microenvironment and inhibiting the progression of PCa. The current results indicated that the expression of SERPINA3 may be negatively correlated with CRPC, and it could promote the M1 polarization of macrophages and inhibit the progression of CRPC by increasing the expression of CXCL2.
Evaluation of cytokine levels in HIV-infected individuals on therapy with tenofovir, lamivudine, and dolutegravir.
Silva-Junior CDD, Silva BA, Gonçales JP … +7 more , Silva MMD, Moreira LR, Barros MS, Rabello MCS, Araújo PSR, Lorena VMB, Moura LCRV
Braz J Med Biol Res · 2025 · PMID 40367013 · Full text
Antiretroviral therapy (ART) is essential to reduce viral load and restore CD4+ T cell levels in people living with HIV/AIDS (PLWHA). However, different treatment protocols influence the levels of cytokines, important me...
Antiretroviral therapy (ART) is essential to reduce viral load and restore CD4+ T cell levels in people living with HIV/AIDS (PLWHA). However, different treatment protocols influence the levels of cytokines, important mediators of the immune response. This study aimed to evaluate cytokine levels in PLWHA on therapy with tenofovir (TDF), lamivudine (3TC), and dolutegravir (DTG). The results showed that PLWHA on treatment had a significant increase in CD4+ T lymphocyte levels and a reduction in CD8+ T lymphocyte levels compared to naive (untreated) individuals. Furthermore, PLWHA treated with TDF/3TC/DTG had a significant reduction in interleukin (IL)-4 and IL-10 levels (P<0.02; P=0.047) compared to other ART regimens. Naive individuals had higher levels of IL-2 and interferon (IFN)-γ, while their levels of tumor necrosis factor (TNF), IL-4, and IL-10 were lower. These findings suggested that TDF/3TC/DTG treatment modulated cytokines, reducing chronic inflammation and improving the immune response in PLWHA. The decrease in anti-inflammatory cytokines, such as IL-4 and IL-10, may be associated with better regulation of the immune system, resulting in greater control of infection and a balanced inflammatory response.
Single-cell analysis reveals potential therapeutic markers of peripheral blood mononuclear cells from bladder cancer patients.
Mao X, Yang R, Yan Y … +9 more , Zeng Y, Bao M, Huang R, Dai Y, Zhang Q, Ye Y, Cheng J, Mo Z, Zhang H
Braz J Med Biol Res · 2025 · PMID 40367012 · Full text
Bladder cancer is the most prevalent malignancy of the urinary tract, with significant advancements in treatment achieved over recent decades. Nonetheless, the immunological mechanisms underlying bladder cancer progressi...
Bladder cancer is the most prevalent malignancy of the urinary tract, with significant advancements in treatment achieved over recent decades. Nonetheless, the immunological mechanisms underlying bladder cancer progression remain elusive, and only a limited number of patients derive benefit from current immune checkpoint inhibitors. Here, we conducted a single-cell RNA sequencing analysis of 44,022 cells from peripheral blood mononuclear cell samples of bladder cancer patients and a healthy donor. Our findings indicated that the proportions of T cells and neutrophils are higher in bladder cancer patients than in the healthy donor. LAG3, HAVCR2, and CTLA4 had elevated expression levels in CD8-T2-GZMK cell clusters from patients. CD8-T7-STMN1 cells highly expressed ITGAE, CD38, and STMN1. Furthermore, NK3-CMC1, more prevalent in patients, showed a high expression of TIGIT. Additionally, Bcell2-TCL1A and Bcell3-MS4A1 were characterized by the high expression of inhibitory receptor marker genes. Gene set variation analysis suggested that Mono4-THBS1 may play a role in promoting tumor hypoxia and angiogenesis. Neu-FCGR3B exhibited high levels of IL4R and CD274 expression. Our study indicated that LAG-3 and TIM-3 may serve as novel potential immune checkpoint inhibitors in bladder cancer treatment. The phenotypes of NK3-CMC1, Bcell2-TCL1A, and Bcell3-MS4A1 might be altered by tumor progression. Mono4-THBS1 could potentially be a source of tumor-enriched monocyte-like cells. Neu-FCGR3B may play a detrimental role in the anti-tumor response and could emerge as a predictive marker for bladder cancer. Overall, these high-resolution transcriptomic data offer invaluable insights for identifying new therapeutic targets and biomarkers in bladder cancer immunotherapy.
Systemic effects of oral tolerance improve the healing of several and concomitant wounds on different parts of the body.
Nobrega IBC, Andrade AVS, Bikat TJN … +5 more , Quintão GM, Azevedo Junior GM, Franco-Valência K, Costa RA, Carvalho CR
Braz J Med Biol Res · 2025 · PMID 40243821 · Full text
Oral tolerance is an immunological phenomenon that results from protein intake and that has systemic effects on inflammation. Previous research has shown that parenteral injection of tolerated proteins reduces inflammato...
Oral tolerance is an immunological phenomenon that results from protein intake and that has systemic effects on inflammation. Previous research has shown that parenteral injection of tolerated proteins reduces inflammatory infiltrate and improves skin wound healing. Herein, we tested whether the injection of tolerated proteins improves the healing of several wounds on different parts of the body, such as on the skin of the back and on the external ear (the auricle). To induce oral tolerance to ovalbumin (OVA), eight-week old C57BL/6 mice drank egg white diluted 1:5 in water for 3 consecutive days. The control mice drank water. Seven days after oral treatment, mice were submitted to excisional injuries on the skin of the back (6 mm) and ears (4 mm). Minutes before the injuries, the mice received an intraperitoneal injection of OVA + Al(OH)3. Seven and 40 days after the injuries, tissue samples were collected and processed for histological analysis of the wounds. The results showed that the injection of OVA in animals that drank OVA reduced the inflammatory infiltrate in all lesions. In addition, injection of OVA in animals that drank OVA promoted better organization of the extracellular matrix, with thicker and intertwined collagen fibers in the neodermis, resulting in smaller scars on the skin. Furthermore, the healing area of the ears of OVA-tolerant animals showed chondrocyte aggregates and less obvious fibrous scar tissue compared with control animals. In conclusion, systemic effects of oral tolerance positively influenced the healing of several lesions on different parts of the body.
Oleanolic acid enhanced the anticancer effect of fluorouracil by regulating Ca2+ levels in hepatocellular carcinoma cells.
Dong J, Gao Y, Li P … +6 more , Chen P, Lv Y, Liu Y, Zhang S, Zhang M, Wang Y
Braz J Med Biol Res · 2025 · PMID 40243820 · Full text
Oleanolic acid (OA) is recognized for its anticancer properties, which are similar to those of conventional chemotherapeutic agents used in clinical practice. However, its role in modulating the sensitivity of cancer cel...
Oleanolic acid (OA) is recognized for its anticancer properties, which are similar to those of conventional chemotherapeutic agents used in clinical practice. However, its role in modulating the sensitivity of cancer cells to fluorouracil (5FU) has not yet been documented. This study aimed to examine the effects of OA and 5FU co-administration on hepatocellular carcinoma (HCC) and uncover the mechanisms involved. In this study, the efficacy of combination therapy with OA and 5FU in treating HCC was evaluated using the MTT cell proliferation assay, plate clone formation assay, Hoechst 33342 staining, western blot assay, and Ca2+ fluorescence probe. The results demonstrated that compared with the use of OA or 5FU alone, OA and 5FU combination therapy significantly inhibited the proliferation of HEPG2 cells and enhanced cell apoptosis and Ca2+ levels in HCC. Additionally, the inhibitory effect of OA and 5FU combination therapy on cell proliferation and apoptosis was partially reversed by the calcium channel blocker 2-aminoethyldiphenyl borate (2-APB). In summary, these findings indicated that synergistic treatment with OA and 5FU can enhance cell apoptosis, inhibit cell proliferation, and regulate Ca2+ signaling in HCC, providing new guidance for the clinical treatment of HCC.
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