Dallavecchia DL, Lima E Silva AA, Debelian ACM
… +2 more, Aguiar VM, Silva Filho RG
Braz J Med Biol Res
· 2025 · PMID 40960776
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The therapeutic benefits obtained from the presence of larvae of certain flies in infected wounds have been mentioned since ancient times. Currently, the so-called maggot therapy or biosurgery is considered a simple, saf...The therapeutic benefits obtained from the presence of larvae of certain flies in infected wounds have been mentioned since ancient times. Currently, the so-called maggot therapy or biosurgery is considered a simple, safe, relatively low-cost, and highly effective alternative for treating a wide variety of infected, necrotic, and difficult-to-heal wounds, including those caused by multidrug-resistant bacteria. In addition to the debridement of necrotic wound tissue promoted by larvae, especially from the green bottle fly (Lucilia sericata; Diptera: Calliphoridae), there is much evidence that their native excretions and secretions (NES) contain components with varied antimicrobial activity against Gram-positive and Gram-negative bacteria and activity against fungi. Furthermore, studies have shown the antibiofilm effect of NES. Biofilms represent an additional problem for wound healing because they prevent the action of antibiotics on the pathogens infecting the wound. The antimicrobial effects of crude NES or its molecular components described in studies sometimes present contrasting results when compared. This is probably due to the laboratory methodological aspects used, which range from the preparation of larvae and extraction of NES to the tests used to evaluate their antimicrobial activity. This review aimed to bring together a diversity of laboratory procedures and results that have been described for the antimicrobial potency of NES. Moreover, it aimed to contribute to a greater standardization of the methodologies adopted in new studies to generate more consensual and comparable results.
Braz J Med Biol Res
· 2025 · PMID 40960775
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The aim of this study was to investigate the correlation between pre-stroke frailty status and post-stroke cognitive impairment (PSCI) in patients with acute large artery atherosclerotic cerebral infarction. One hundred...The aim of this study was to investigate the correlation between pre-stroke frailty status and post-stroke cognitive impairment (PSCI) in patients with acute large artery atherosclerotic cerebral infarction. One hundred and eight patients with acute large artery atherosclerotic cerebral infarction admitted in our hospital from July 2020 to July 2023 were prospectively enrolled. Patients were stratified into frailty (46 cases) and non-frailty groups (62 cases) based on FRAIL scale scores. During the 6-month follow-up after the onset of cerebral infarction, patients were evaluated using the Chinese modified version of Montreal Cognitive Assessment (MoCA) scale for cognitive function and were divided into PSCI (52 cases) and non-PSCI (56 cases) groups. The frailty group showed significantly higher age, prevalence of hypertension and diabetes comorbidities, smoking and alcohol consumption rates, National Institutes of Health Stroke Scale (NHISS) score, and Modified Rankin Scale (mRS) score than those in the non-frailty group (P<0.05, P<0.01). The incidence of PSCI in the frailty group was also significantly higher than that in the non-frailty group (78.3 vs 25.8%, P<0.01). Compared to the non-PSCI group, the PSCI group had higher age, shorter education duration, fewer cases of reperfusion therapy, and greater frailty (P<0.05, P<0.01). Logistic regression analysis showed that pre-stroke frailty was an independent risk factor for PSCI (P<0.01). Timely assessment of the frailty status in patients with acute large artery atherosclerotic cerebral infarction is beneficial for preventing, delaying onset, and reducing the incidence of PSCI.
Neiva JCB, Fernandes MDB, Toralles MBP
… +7 more, Andrade RS, Erfani KJ, Maia MEF, Santana JM, Silva IMM, Reis JBL, Klein SOT
Braz J Med Biol Res
· 2025 · PMID 40960774
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Breast cancer is the most frequent neoplasm and has the highest mortality rate among women. In the Afro-descendant population, these tumors may appear earlier and assume a more aggressive behavior. This study aimed to as...Breast cancer is the most frequent neoplasm and has the highest mortality rate among women. In the Afro-descendant population, these tumors may appear earlier and assume a more aggressive behavior. This study aimed to assess the epidemiological and clinical behavior of breast cancer in a predominantly Afro-descendant population, identify risk and prognostic factors, and compare them with already available data. Clinical and sociodemographic data were obtained from medical records and interviews with the patients involved. The variables ethnicity, age, number of children, monthly income, and education were used to describe the epidemiological profile and the results of clinical evaluation and pathological anatomy study. The immunohistochemical analysis was used to correlate the clinical characteristics of the tumors and prognosis. Afro-descendant women represented 77% of the population and the mean age at diagnosis was 54.4 years. Approximately 75% had up to 2 children, 20.5% had low income, and 37.3% had a low level of education. Infiltrating ductal carcinoma was diagnosed in 91% of patients, 70.2% had a moderate degree of differentiation, luminal subtype A was the most prevalent (39%), and a higher than global average percentage had a triple negative profile (22.9%). Early stages were identified in 53.4% of patients and only 4.8% were diagnosed with metastatic disease. The recurrence rate was 11.6%, and the mortality rate was 6.8%. The present study showed that unfavorable sociodemographic and clinical aspects, such as the high prevalence of triple-negative tumors, were not associated with a worse prognosis.
Braz J Med Biol Res
· 2025 · PMID 40960773
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Glioblastoma (GBM) is the most prevalent tumor in the central nervous system in adults. Lactotransferrin (LTF) is a molecule involved in the growth of various tumors. However, the underlying mechanism of LTF in GBM progr...Glioblastoma (GBM) is the most prevalent tumor in the central nervous system in adults. Lactotransferrin (LTF) is a molecule involved in the growth of various tumors. However, the underlying mechanism of LTF in GBM progression and chemotherapy resistance remains unclear. In this study, the clinical and diagnostic value of LTF were evaluated. In vitro and in vivo experiments were performed to explore the functional role of LTF in GBM. Immunoprecipitation and immunofluorescence assays were performed to clarify the effect of LTF on nuclear factor-κB (NF-κB) activation. LTF was overexpressed in GBM and correlated with poor prognosis. LTF promoted GBM cell proliferation, invasion, and temozolomide (TMZ) resistance. Mechanism assay results indicated that LTF competitively binds to p65, rescuing the inhibited effect of PP2A on p65 phosphorylation, thereby activating the NF-κB signaling pathway. Our results confirmed that highly expressed LTF promoted GBM progression and TMZ resistance through the NF-κB signaling pathway.
Elmas S, Cekic EG, Cenik P
… +4 more, Sirinyildiz F, Elmas O, Elmas O, Cesur G
Braz J Med Biol Res
· 2025 · PMID 40900465
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Serum biomarkers are crucial for identifying complications of obesity. This study evaluated serum levels of leptin, vascular endothelial growth factor (VEGF), myeloperoxidase (MPO), C-reactive protein (CRP), oxidized low...Serum biomarkers are crucial for identifying complications of obesity. This study evaluated serum levels of leptin, vascular endothelial growth factor (VEGF), myeloperoxidase (MPO), C-reactive protein (CRP), oxidized low-density lipoprotein (OXLDL), low-density lipoprotein (LDL), and other biochemical parameters in a rat model of high-fat diet (HFD)-induced obesity to investigate potential relationships between these biomarkers and microvascular function. Rats in the HFD group were fed a high-fat diet for 23 weeks, whereas control rats received a standard diet. Microvascular function was assessed using the post-occlusive reactive hyperemia (PORH) test; PORH responses were measured in the right forelimbs using laser Doppler flowmetry. Serum samples were then collected to measure the aforementioned biomarkers. Results showed decreased PORH responses in the HFD group, indicating impaired microvascular function. Serum levels of leptin, MPO, CRP, LDL, and OXLDL were significantly higher in the HFD group. Strong correlations were observed between microvascular dysfunction and LDL, OXLDL, MPO, and CRP. No significant changes were found in VEGF or HDL levels. These findings suggest that increased LDL oxidation to OXLDL in obesity contributes to vascular impairment, likely due to increased oxidative stress and inflammation mediated by elevated MPO and CRP. Further research focusing on the roles of LDL, OXLDL, MPO, and CRP may provide deeper insights into the mechanisms underlying microvascular dysfunction in obesity.
Braz J Med Biol Res
· 2025 · PMID 40900464
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Cervical cancer remains a leading cause of cancer-related mortality among women worldwide, despite treatment advances. The most common form is squamous cell cervical carcinoma, primarily associated with human papillomavi...Cervical cancer remains a leading cause of cancer-related mortality among women worldwide, despite treatment advances. The most common form is squamous cell cervical carcinoma, primarily associated with human papillomavirus (HPV) type 16. Chrysin (5,7-dihydroxyflavone) is a natural flavonoid with promising anticancer properties both in vitro and in vivo. The aim of this study was to evaluate the antiproliferative, anti-migratory, and anti-invasive effects of chrysin on the SiHa human cervical cancer cell line (HPV-16-positive) using a 3D cell culture model with spheroids. Cell viability was assessed using the resazurin assay, while cytostatic effects were monitored by measuring spheroid size through imaging. Migration was evaluated with the spheroid migration assay. The expression of matrix metalloproteinase (MMP)-2, MMP-9, and vascular endothelial growth factor (VEGF) was quantified by immunoenzymatic assays. Chrysin treatment exhibited concentration-dependent cytotoxic and cytostatic effects, reducing cell proliferation and decreasing SiHa spheroid size. Additionally, chrysin inhibited cell migration and invasion, potentially reducing metastatic potential, primarily by decreasing the production of MMP-2 and VEGF. These findings suggest that chrysin has therapeutic potential for squamous cell cervical carcinoma and warrants further in vivo preclinical studies.
Walsh-Monteiro A, Morato S, Uribe FAR
… +2 more, Gouveia A, Pedroso JS
Braz J Med Biol Res
· 2025 · PMID 40900463
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This systematic review investigates the effects of the ayahuasca beverage (Aya) in various animal models. Using the PRISMA protocol and adhering to the Cochrane Handbook for Systematic Reviews, a comprehensive selection...This systematic review investigates the effects of the ayahuasca beverage (Aya) in various animal models. Using the PRISMA protocol and adhering to the Cochrane Handbook for Systematic Reviews, a comprehensive selection of 2,359 documents was identified from the Web of Science, Medline, and Scopus databases between 2012 and 2022. Following the inclusion and exclusion criteria, 14 articles were included in the final analysis. The analysis revealed a diversity in the selection of animal models that included different developmental stages and various forms of Aya intoxication, including acute and chronic doses, and varying concentrations of the active principles. The studies revealed that Aya causes significant alterations in the motor and cognitive behavior of animals, especially associated with the serotonergic system, which seems to contribute to the negative symptoms also observed in schizophrenia and depression. Despite the evidence found, this review highlights the scarcity of more robust pre-clinical studies with methodological standardization to make more conclusive comparisons, especially given the need to identify potential toxic and neurochemical effects of Aya on organisms for a safer assessment of its therapeutic use.
Braz J Med Biol Res
· 2025 · PMID 40900462
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This study aimed to evaluate the effects of the ketamine-xylazine (KX) anesthetic mixture on autonomic and cardiovascular functions in normotensive rats (Wistar) and spontaneously hypertensive rats (SHR), using both spec...This study aimed to evaluate the effects of the ketamine-xylazine (KX) anesthetic mixture on autonomic and cardiovascular functions in normotensive rats (Wistar) and spontaneously hypertensive rats (SHR), using both spectral and symbolic analyses. Male Wistar (n=22) and SHR (n=28) rats were intramuscularly anesthetized with KX, and their femoral artery and vein were cannulated for pulsatile arterial pressure recording and drug administration. Autonomic function was assessed 24 and 48 h post-surgery through spectral and symbolic analyses of heart rate (HR) and systolic arterial pressure (SAP) variability. KX anesthesia significantly decreased mean arterial pressure (MAP) 24 h post-surgery in both Wistar and SHR rats. Spectral analysis revealed increased sympathetic modulation in the vascular bed of SHR 48 h post-surgery. In Wistar rats, there was a significant reduction in parasympathetic modulation at 48 h, as indicated by root mean square of successive RR interval differences (RMSSD) and high frequency (HF) (nu) indices. Symbolic analysis, however, detected no significant changes in autonomic modulation. These data are consistent with the notion that KX anesthesia significantly impacts autonomic and cardiovascular functions, with differential effects observed between Wistar and SHR rats. Spectral analysis proved more effective than symbolic analysis in detecting these changes. These findings highlight the need for careful consideration of anesthetic effects in experimental research and suggest that optimizing anesthetic protocols could improve clinical outcomes by minimizing adverse autonomic impact.
Zhou X, Li Y, Zhang X
… +4 more, Zhang M, Zhang R, Sun S, Li G
Braz J Med Biol Res
· 2025 · PMID 40900461
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The aim of this study was to evaluate the dynamic variations in the quantitative parameters of diffusion-weighted imaging (DWI) at different b-value combinations in a prostate cancer (PCa) mouse model for noninvasive mon...The aim of this study was to evaluate the dynamic variations in the quantitative parameters of diffusion-weighted imaging (DWI) at different b-value combinations in a prostate cancer (PCa) mouse model for noninvasive monitoring of histopathological changes. Twenty-five male C57BL/6J mice were randomly allocated into a control group (n=5) or an experimental group (n=20). The experimental groups were used to establish the PCa model. On days 9, 12, 15, and 18 post-modeling, 5 mice were randomly selected for MRI, including T1WI, T2WI, T2WI SPIR, and DWI. The b-values were set at 0, 500, 1000, 1500, and 2000 s/mm2. Apparent diffusion coefficient (ADC) and exponential apparent diffusion coefficient (EADC) values from different b-value combinations were measured. Post-MRI, tumors were excised for histopathological analysis. DWI quantitative parameters, tumor nuclear fraction, and Ki-67 area fraction were compared on different days, along with correlation analysis. ADC values gradually decreased as tumor progressed, whereas EADC values gradually increased. Tumor nuclear fraction increased over time. Ki-67 increased first and then decreased. Tumor nuclear fraction was negatively correlated with the ADC value and positively correlated with the EADC value. The Ki-67 was positively correlated with the ADC value and negatively correlated with the EADC value. ADC values at b=1000, 1500 s/mm2 and the EADC values at b=0, 500 s/mm2 demonstrated the strongest correlations with the tumor nuclear fraction; the ADC and EADC values at b=500, 1000 s/mm2 were more strongly correlated with Ki-67, being potential noninvasive imaging biomarkers for monitoring changes in tumor histopathology.
Amorim JL, Bensenor IM, Alencar AP
… +4 more, Pereira AC, Goulart AC, Lotufo PA, Santos IS
Braz J Med Biol Res
· 2025 · PMID 40862459
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It is unclear who benefits the most from atherosclerotic cardiovascular disease (ASCVD) screening imaging. This study aimed to identify features associated with positive coronary artery calcium scores (CACS) in individua...It is unclear who benefits the most from atherosclerotic cardiovascular disease (ASCVD) screening imaging. This study aimed to identify features associated with positive coronary artery calcium scores (CACS) in individuals with diabetes using machine learning (ML) techniques. ELSA-Brasil is a cohort study with 15,105 participants aged 35 to 74 years in six Brazilian cities. We analyzed 25 sociodemographic, medical history, symptom-related, and laboratory variables from 585 participants from the São Paulo investigation center with CACS data and no overt cardiovascular disease at baseline. We used six ML algorithms to build models to identify individuals with positive CACS. Feature importance was determined by SHapley Additive exPlanations (SHAP) values. The best performer ML algorithm was the XGBoost Classifier (accuracy: 94.8%). Age (SHAP: 0.220), systolic blood pressure (SHAP: 0.102), and body mass index (SHAP: 0.075) were the most important variables to identify ASCVD in individuals with diabetes in XGBoost models. Considering all ML models in our analysis, age, systolic blood pressure, and sex were frequently influential variables. We obtained high accuracy with our best model, using information generally present in current clinical practice. ML models may help clinicians select patients with characteristics most probably associated with a positive CAC. Age, systolic blood pressure, body mass index, and sex may be useful markers to identify those at higher risk for subclinical ASCVD.
Zhu L, Guo M, Wang L
… +3 more, Chen S, Ye Z, Wu Y
Braz J Med Biol Res
· 2025 · PMID 40862458
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Keratinocyte hyperproliferation and excessive inflammatory responses are associated with psoriasis pathogenesis. Trifolirhizin has anti-inflammatory and anti-proliferation effects. The purpose of the study was to investi...Keratinocyte hyperproliferation and excessive inflammatory responses are associated with psoriasis pathogenesis. Trifolirhizin has anti-inflammatory and anti-proliferation effects. The purpose of the study was to investigate the role of trifolirhizin in psoriasis-like skin lesions and its molecular mechanism. Imiquimod-induced psoriasis-like mouse models were treated with trifolirhizin. Skin lesions and inflammatory factors were assessed. In vitro, human HaCaT keratinocytes were stimulated by a mixture of interleukin (IL)-1α, IL-17, IL-22, tumor necrosis factor (TNF)-α, and oncostatin M (M5) to establish a psoriatic keratinocyte model. Cell viability and cycle were assessed via CCK-8 assay and flow cytometry. Inflammatory factors, autophagy levels, and AMPK-mTOR pathway activation were detected by western blot. Trifolirhizin dose-dependently inhibited epidermal layer erythema, scaling, and thickening and reduced epidermal thickness and IL-12 level in an imiquimod-induced psoriasis-like mouse model. Trifolirhizin also inhibited cell viability, PCNA expression, and excessive synthesis and secretion of IL-8 and IL-12 in HaCaT keratinocytes induced by M5. Furthermore, the inhibition of autophagy and AMPK-mTOR pathway could be reversed by trifolirhizin in M5-induced HaCaT keratinocytes and skin lesions from imiquimod-mediated psoriasis-like mouse model. The improvement effects of trifolirhizin could be inhibited by the autophagy inhibitor chloroquine. Trifolirhizin up-regulated autophagy through the AMPK-mTOR pathway, improved the hyperproliferation and excessive inflammatory responses of keratinocytes, thus alleviating psoriatic skin lesions. Trifolirhizin may have therapeutic potential in improving the progression of psoriasis.
Braz J Med Biol Res
· 2025 · PMID 40862457
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This study aimed to systematically evaluate the risk of drug-induced pulmonary edema (DIPE) using the Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database. This retrospective pharmacovigilan...This study aimed to systematically evaluate the risk of drug-induced pulmonary edema (DIPE) using the Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database. This retrospective pharmacovigilance study utilized FAERS data from the first quarter of 2004 to the second quarter of 2024. We identified drugs with at least 10 reported DIPE cases as primary suspects (PS). The DIPE signals were assessed using four methods: Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Empirical Bayes Geometric Mean (EBGM). Multivariate logistic regression was employed to control for confounding factors, and the timing of DIPE onset was statistically analyzed. Out of 173 target drugs, 37 were identified with DIPE risk. The top five drugs were naloxone, dasatinib, nifedipine, anti-thymocyte globulin, and pioglitazone. Multivariate logistic regression indicated that all except pioglitazone were independent risk factors for DIPE. The onset time of DIPE varied by age and gender for some drugs. This study is the first to identify the DIPE risk systematically associated with multiple drugs. It highlights the need for clinicians and pharmacists to be aware of these high-risk drugs and to monitor high-risk populations closely to ensure medication safety.
Braz J Med Biol Res
· 2025 · PMID 40862456
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Statins have been shown to have antifibrotic effects on various tissues and organs, but their ability to improve chronic colitis-associated intestinal fibrosis and their mechanisms of action remain unclear. The objective...Statins have been shown to have antifibrotic effects on various tissues and organs, but their ability to improve chronic colitis-associated intestinal fibrosis and their mechanisms of action remain unclear. The objective of this study was to investigate the role of pitavastatin in chronic colitis-associated intestinal fibrosis and its possible mechanisms. We established a mouse model of chronic colitis-associated intestinal fibrosis through repeated administration of dextran sodium sulfate (DSS) and treated the mice with pitavastatin. The severity of intestinal fibrosis, serum inflammatory factor levels, and expression levels of intestinal fibrosis-related genes in mice were assessed using pathological histological staining, immunohistochemical staining, reverse-transcription PCR, RNA sequencing, and enzyme-linked immunosorbent assay. In vitro, we treated a human colon fibroblast cell line (CCD-18Co) with or without transforming growth factor-β1 stimulation using pitavastatin. Western blot, Cell Counting Kit-8 assay, and Transwell assay were used to analyze the activation of colonic fibroblasts, protein expression levels of genes related to intestinal fibrosis, and cell proliferation and migration abilities. Pitavastatin significantly attenuated DSS-induced chronic colitis and intestinal fibrosis. In vitro, pitavastatin concentration-dependently inhibited the activation of CCD-18Co cells, significantly reduced the expression levels of the intestinal fibrosis-related proteins Col1A1, IGF-1, IGF-1R, MMP-3, and TIMP-1, and significantly inhibited cell proliferation and migration while markedly increasing MMP-9 protein expression. Additionally, after silencing the IGF-1 and IGF-1R genes in CCD-18Co cells, the promotion of MMP-9 expression by pitavastatin was significantly inhibited. These findings suggest that pitavastatin may be a promising antifibrotic drug for future treatment of intestinal fibrosis.
Torezani-Sales S, Damiani APL, Madureira AR
… +7 more, Cordeiro JP, Taufner GH, Nogueira BV, Dias MC, Sugizaki MM, Leopoldo AS, Lima-Leopoldo AP
Braz J Med Biol Res
· 2025 · PMID 40862455
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Obesity is an independent risk factor for metabolic dysfunction-associated steatotic liver disease (MASLD). Non-pharmacological strategies, such as strength training (ST), have been investigated for their effectiveness i...Obesity is an independent risk factor for metabolic dysfunction-associated steatotic liver disease (MASLD). Non-pharmacological strategies, such as strength training (ST), have been investigated for their effectiveness in attenuating MASLD. This study evaluated the effects of ST on hepatic fat accumulation in an experimental model of obesity. Thirty-day-old male Wistar rats (∼150 g) were assigned to either a standard diet (SD) or a high-fat diet (HFD). The experimental protocol lasted 26 weeks and was divided into two phases: 1) obesity induction and maintenance (16 weeks) and 2) ST intervention (10 weeks). After the 16th week, HFD-fed rats were further divided into sedentary obese (Ob) and obese trained (ObST) groups. The ST protocol consisted of 4-5 vertical ladder climbs with 60-s intervals, three times per week, using 50-100% of maximal load. Body weight (BW), fat pads, total body fat (BF), adiposity index (AI), and muscle strength were assessed, as were glycemic, lipid, inflammatory, and histological parameters. ST reduced BW, epididymal and visceral fat depots, triglycerides, total cholesterol, glucose, leptin, and tumor necrosis factor (TNF)-α levels while improving insulin resistance. In conclusion, ST significantly attenuated hepatic steatosis in obesity, promoting metabolic and anti-inflammatory benefits. These findings suggest that ST may be an effective therapeutic strategy for MASLD, and further studies are needed to elucidate its molecular mechanisms and clinical applications.
Braz J Med Biol Res
· 2025 · PMID 40561277
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Obstructive sleep apnea (OSA) is linked to cardiovascular complications, including myocardial dysfunction, yet early detection remains difficult. This retrospective study aimed to develop a combined logistic regression a...Obstructive sleep apnea (OSA) is linked to cardiovascular complications, including myocardial dysfunction, yet early detection remains difficult. This retrospective study aimed to develop a combined logistic regression and QUEST decision tree model to predict early myocardial dysfunction in OSA patients. Echocardiography left ventricular global longitudinal strain (LVGLS) and right ventricular free wall longitudinal strain (RVFWLS) were used to assess myocardial function in OSA patients. Predictive models were constructed using clinical parameters. External validation involved 100 OSA patients from a respiratory sleep clinic. LVGLS and RVFWLS were significantly impaired in OSA patients, particularly in moderate-to-severe cases. BMI, percentage of sleep time with oxygen saturation <90% (CT90%), and arterial bicarbonate were identified as key predictors. The combined model achieved superior predictive accuracy, with an area under the curve of 0.91 for LVGLS and RVFWLS reductions, outperforming individual models. External validation confirmed the stability and generalizability of the model. The combined logistic regression and QUEST decision tree model accurately predicted early myocardial dysfunction in OSA patients, providing a valuable tool for personalized risk assessment and early intervention.
Chang P, Huang H, Huang P
… +3 more, Yi H, Zhong W, Yang Z
Braz J Med Biol Res
· 2025 · PMID 40561276
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Total hysterectomy is a commonly performed gynecological procedure used to treat uterine pathologies. This study aimed to establish a total hysterectomy mouse model and investigate the effect of estradiol valerate on hum...Total hysterectomy is a commonly performed gynecological procedure used to treat uterine pathologies. This study aimed to establish a total hysterectomy mouse model and investigate the effect of estradiol valerate on humoral immune function in BALB/c mice. Our results showed that the ratios of CD4+ and CD8+ subpopulation and hepatitis B virus antibody IgG content were reduced in the total hysterectomy (TH) group compared with the control group (P<0.05). The measured indices showed varying degrees of improvement after estradiol valerate administration. The numbers of CD19+ B lymphocytes significantly increased in the TH group (P<0.05) compared with the control group. There was a significant reduction of the size of germinal centers within lymph nodes in the TH group. This effect was reversed by estrogen supplementation. In summary, reduced estrogen levels following total hysterectomy may impair B lymphocyte activation, IgG secretion, and plasma cell production, leading to compromised immune function. Early treatment with estradiol valerate reverses impaired immune function and enhances antigen-induced antibody production in mice.
Braz J Med Biol Res
· 2025 · PMID 40561275
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Immune regulation plays an important role in the pathogenesis of intervertebral disc degeneration (IDD). However, the mechanism of immune regulation in IDD is still unclear. All IDD data were downloaded from a public dat...Immune regulation plays an important role in the pathogenesis of intervertebral disc degeneration (IDD). However, the mechanism of immune regulation in IDD is still unclear. All IDD data were downloaded from a public database. The differentially expressed (DE) immune-related genes in IDD were identified by the limma package in R. Functional enrichment analyses were performed to explore potential immune-related biological pathways in IDD. We also identified differentially expressed microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) and constructed an mRNA-miRNA-lncRNA network. ROC analysis was performed to reveal potential diagnostic biomarkers for IDD. To understand the potential role of immune cells in IDD, xCell and Pearson correlation analyses were performed. Finally, expression validation was performed using real-time PCR. C5AR2, NFATC2, FCGR3A, hsa-miR-302d-3p, and MIR17HG were identified in IDD. ROC analysis results suggested that C5AR2 had good diagnostic accuracy, and FCGR3A and NFATC2 had sufficient diagnostic accuracy, which implied that they may be potential diagnostic markers of IDD. We also found that a large number of immune-related signaling pathways, such as cytokine-cytokine receptor interaction, chemokine signaling pathway, toll-like receptor signaling pathway, and Nod-like receptor signaling pathway, were significantly enriched. C5AR2, hsa-miR-302d-3p, and MIR17HG were significantly correlated with multiple immune cell types, such as cDC, CD8+ Tem, macrophage M1, neutrophils, and plasma cells. The C5AR2-hsa-miR-302d-3p-MIR17HG axis may play a role in immune regulation by regulating the infiltration level of related immune cells in the IDD microenvironment. The identification of key immune-related molecules, cells, and signaling pathways in IDD is of great significance to reveal the pathogenesis of IDD.
Braz J Med Biol Res
· 2025 · PMID 40561274
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Obesity is a serious health problem worldwide and the search for new control methods and therapies is imperative. Studies indicate that a variety of obesogenic diets may increase the risk of developing type 2 diabetes me...Obesity is a serious health problem worldwide and the search for new control methods and therapies is imperative. Studies indicate that a variety of obesogenic diets may increase the risk of developing type 2 diabetes mellitus (T2D) by causing insulin resistance in peripheral tissues. The chronic increase in free fatty acids associated with obesity may increase insulin demand by pancreatic beta cells and induce intrinsic beta cell dysfunction through endoplasmic reticulum (ER) stress, which is associated with beta cell loss during the development of T2D. Physical exercise approaches have been emerging as powerful tools and adjuncts in a variety of conditions, improving glucose homeostasis, oxygen uptake, and metabolism. Here, we showed that a 16-week endurance training program mitigated the deleterious effects of an obesogenic diet on glycemic homeostasis, insulin secretion, and ER stress markers as well as islet health markers in C57/BL6 obese mice. The results corroborated the assumption that physical exercise is an effective therapy to avoid beta cell death in glucose metabolism dysfunction and T2D in obese individuals.
Braz J Med Biol Res
· 2025 · PMID 40561273
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Oxidative stress plays a key role in the mechanisms underlying pathophysiological processes, such as inflammation, age-related degenerative phenomena, atherosclerosis, hypertension, cancer, diabetes mellitus, neurodegene...Oxidative stress plays a key role in the mechanisms underlying pathophysiological processes, such as inflammation, age-related degenerative phenomena, atherosclerosis, hypertension, cancer, diabetes mellitus, neurodegenerative diseases, xenobiotic toxicity, among others. It is generated by the production of free radicals, resulting from the oxidative metabolism of cells. Oxidative stress is an important defense against infections. It acts specifically as a vasodilator and helps modulate antioxidant mechanisms. However, the effects become harmful when its production increases or antioxidant mechanisms are excessively reduced. Toxic metals from environmental and occupational exposure are silent agents that induce oxidative stress. Metals such as mercury (Hg), aluminum (Al), cadmium (Cd), and lead (Pb) are known to be toxic to various organs and tissues in our body. The present mini-review focuses on the cardiovascular system, considering that the interplay between oxidative stress and toxic metals acting silently is involved in their harmful effects, especially on the etiopathogenesis of cardiovascular disorders. A brief review is also given regarding the mechanisms of modulation of redox homeostasis by organic mechanisms, pharmacological approaches that can act directly or indirectly as antioxidants, and food-derived compounds that appear to be effective inhibitors of oxidative stress, thus preventing the harmful effects of free radicals.