Braz. J. Med. Biol. Res. [JOURNAL]
Sun
200 papers
PD-1 involvement in CD8+ tumor-infiltrating lymphocytes in patients with colonic-derived peritoneal adenocarcinoma.
Hu H, Zhang M
Braz J Med Biol Res · 2025 · PMID 40243819 · Full text
Immune checkpoint blockade with anti-programmed cell death protein 1 (PD-1) antibody has become a hot topic for the treatment of human malignancies. Here, we aimed to investigate whether the percentage of PD-1 in CD8+ tu...
Immune checkpoint blockade with anti-programmed cell death protein 1 (PD-1) antibody has become a hot topic for the treatment of human malignancies. Here, we aimed to investigate whether the percentage of PD-1 in CD8+ tumor-infiltrating lymphocytes correlates with the progression of colonic-derived peritoneal adenocarcinoma (PA). Peripheral blood and tissue samples from 40 patients with colonic-derived PA were collected and subjected to multicolor flow cytometry analysis of the percentage of peripheral PD-1+CD8+ T cells. The multiple immunofluorescence method was used to detect the positive percentages of PD-1 and CD8 in the tissues. The enrolled patients were divided into groups by recurrence interval (less than 6 months, greater than two years) and differentiation grade (low, well/moderate). In the colonic-derived PA tissues, the percentages of cells positive for PD-1, CD8, and PD-1+CD8+ were higher in the paracancer tissues compared with cancerous tissues. PD-1+CD8+ T cells had an increased presence in peripheral blood than in tissues. Our data also indicated that colonic-derived PA patients with less than a six-month recurrence interval presented higher levels of PD-1 in CD8+ tumor-infiltrating lymphocytes in than the two-year recurrence group. The level of PD-1+CD8+T cells in the tissue correlated with the clinical outcome of colonic-derived PA. Higher percentages of PD-1+CD8+T cells correlated with a shorter progression-free survival (PFS). PD-1 in CD8+ tumor-infiltrating lymphocytes may have a good predictive value for immunotherapy of colonic-derived PA and act as the prognostic factor for PFS.
Liraglutide improves antioxidant defense in hearts of spontaneously hypertensive female rats independently of changes in blood pressure in a pre-clinical model of menopause.
Santos WCD, Ronchi SN, Gonçalves LA … +6 more , Oliveira LCSL, Sousa GJ, Melo Junior AF, Andrade TU, Bissoli NS, Brasil GA
Braz J Med Biol Res · 2025 · PMID 40243818 · Full text
Liraglutide (LIRA) is an agonist of the GLP-1 receptor used in the treatment of type 2 diabetes with a cardioprotective effect, although little is known about the effects of LIRA in post-menopause. We aimed to evaluate t...
Liraglutide (LIRA) is an agonist of the GLP-1 receptor used in the treatment of type 2 diabetes with a cardioprotective effect, although little is known about the effects of LIRA in post-menopause. We aimed to evaluate the effects of LIRA in the cardiovascular system of ovariectomized spontaneously hypertensive rats (SHR). SHR rats were separated into two groups: ovariectomized (saline) and ovariectomized + liraglutide (0.6 and 1.2 mg/kg for 4+4 weeks, respectively). Systolic blood pressure (SBP) was indirectly evaluated at the beginning and end of treatment. Diastolic, systolic, and mean blood pressure were evaluated in the carotid artery of anesthetized animals, while left ventricle systolic blood pressure (LVSBP) and left ventricle derivatives (-dP/dt; +dP/dt) were evaluated in the left ventricle. An oral glucose tolerance test (GTT) was conducted. Antioxidant enzymes and calcium-handling proteins were analyzed in heart tissue by western blot. Treatment with LIRA increased the expression of antioxidant enzymes (superoxide dismutase (SOD2) and catalase). No changes were observed in the GTT, cardiac hemodynamics, blood pressure, and calcium-handling protein expression. A decrease in visceral fat depot was observed without changes in final body weight. LIRA induced an antioxidant subclinical effect in ovariectomized SHR female rats without changing glucose metabolism and cardiac blood pressure.
Aerobic capacity evaluation of Sprague Dawley rats in treadmill running: comparison between protocols.
Dellavechia-De-Carvalho C, Rebelo MA, De-Moraes C … +1 more , Papoti M
Braz J Med Biol Res · 2025 · PMID 40243817 · Full text
The objective of the present study was to compare and test the applicability of different protocols for accessing aerobic capacity in Sprague Dawley rats using treadmill running. Fifteen 70-day-old adult Sprague Dawley r...
The objective of the present study was to compare and test the applicability of different protocols for accessing aerobic capacity in Sprague Dawley rats using treadmill running. Fifteen 70-day-old adult Sprague Dawley rats (270-290 g) were used. After 5 days of adaptation to the treadmill, the animals underwent 7 days of evaluations with a 48-h interval between each protocol. On the first two days, they underwent, in random order, a graded exercise test, with (GXT2) or without (GXT1) blood sample collections to determine blood lactate concentrations and the anaerobic threshold. In the subsequent 4 days, they underwent continuous 30-min efforts to determine the maximal lactate steady state (MLSS) with the intensity prescribed in percentages of the maximum speed (MaxS) obtained in GXT1, and on the last day they underwent the minimum lactate (ML) protocol. The MaxS obtained in GXT2 was higher than in GXT1, and there was a moderate correlation (r=0.614, P=0.011) between them. In many cases, lactate and glucose blood concentrations did not show the expected kinetics, making aerobic capacity determination impossible using these protocols. MLSS showed a higher success rate compared to other protocols (MLSS=80%; GXT2=47%; ML=60%). In conclusion, with the MLSS protocol, it is only possible to measure time to exhaustion at each intensity, which does not exactly reflect aerobic capacity, and the use of blood lactate and glucose concentrations to evaluate the aerobic capacity of rats in incremental and ML treadmill running protocols is still discouraged.
Low-intensity pulsed ultrasound inhibits chondrocyte senescence by inhibiting PI3K/AKT/mTOR signaling.
Han W, Guan M, Liao B … +7 more , Han X, Li K, Chen Q, Guo X, Niu Y, Zhu Y, Bai D
Braz J Med Biol Res · 2025 · PMID 40136230 · Publisher ↗
Cellular senescence is an important cause of age-related degenerative diseases, including osteoarthritis (OA). Chondrocyte senescence is crucial in OA onset and progression. As a non-invasive, safe, and widely used physi...
Cellular senescence is an important cause of age-related degenerative diseases, including osteoarthritis (OA). Chondrocyte senescence is crucial in OA onset and progression. As a non-invasive, safe, and widely used physical rehabilitation factor, the effect and mechanism of low intensity pulsed ultrasound (LIPUS) on chondrocyte senescence remain unclear. This study evaluated the inhibitory effect of LIPUS on OA chondrocyte senescence in vitro and in vivo. The effect of LIPUS on chondrocyte senescence was examined by RT-qPCR, enzyme-linked immunosorbent assay (ELISA), and western blotting. Changes in levels of reactive oxygen species (ROS) and γ-h2ax foci in senescent chondrocytes were detected using fluorescent staining. Chondrocyte senescence was evaluated by senescence-associated β-galactosidase (SA-β-gal) staining. The PI3K inhibitor LY294002 and the PI3K agonist 740Y-P were used to investigate whether PI3K/AKT/mTOR signalling was involved in the effect of LIPUS in senescent chondrocytes. Chondrocyte senescence and cartilage degeneration were analyzed in a destabilization of the medial meniscal (DMM) mouse model by immunohistochemistry, hematoxylin and eosin staining, and safranin-O/fast green staining. LIPUS inhibited the expression of the senescence-associated secretory phenotype (SASP) factors CCL4 and CCL2 and the senescence phenotype in doxorubicin-treated chondrocytes by inhibiting the PI3K/AKT/mTOR pathway. LIPUS alleviated chondrocyte senescence and attenuated OA progression in the DMM mice. These results demonstrated a novel role for LIPUS in inhibiting chondrocyte senescence and the SASP by modulating PI3K/AKT/mTOR signalling. Our findings expanded the clinical application of LIPUS and provide a new, non-invasive, and safe treatment approach to prevent and treat age-related degenerative joint disorders.
Potential of N-acetylcysteine in the management of low back pain: a scoping review of studies in humans and animal models.
Sinigaglia G, Fortunato LM, Grillo ML … +1 more , Partata WA
Braz J Med Biol Res · 2025 · PMID 40136229 · Publisher ↗
Low back pain (LBP) is a common type of pain that causes disability and impairs cognitive function. With over 80% of adults estimated to experience LBP during their lifetime, this type of pain not only has a significant...
Low back pain (LBP) is a common type of pain that causes disability and impairs cognitive function. With over 80% of adults estimated to experience LBP during their lifetime, this type of pain not only has a significant impact on the individual, but also on public health systems and national economies. Unfortunately, there is no single standard of care for patients with LBP. N-acetylcysteine (NAC), which is used clinically to treat acetaminophen overdose, has recently been tested as a potential treatment for LBP. NAC is inexpensive and commercially available, and it has an established tolerance and safety profile. However, NAC's efficacy in LBP has not been established. This scoping review presents a summary of studies investigating the effects of NAC and the potential benefits in LBP treatment, and highlights its potential molecular mechanisms and side effects. A systematic literature search in Pubmed/MEDLINE, Embase, Scopus, Science Direct, Web of Science, Cinahl, and Lilacs databases was conducted. The PRISMA-ScR checklist was used to ensure integrity of the review. The scoping review protocol was registered in the Open Science Framework. No limit was set on study language and publication date. In total, 2357 articles were located, of which 16 were included. The studies show that NAC has potential for LBP treatment, but data are derived only from a few clinical trials and preclinical studies. Thus, there is much to learn and more clinical studies should be performed before NAC can be clinically recommended for the treatment of LBP.
Dynactin knockdown leads to synuclein aggregation by blocking autophagy in a zebrafish model of Parkinson's disease.
Wu Y, Guo Q, Gan J … +12 more , Duan L, Zhao H, Tai H, Yang C, Li Y, Xu Z, Yao Y, Nie Z, Yang M, Li S, Li J, Su B
Braz J Med Biol Res · 2025 · PMID 40136228 · Publisher ↗
Axons of dopaminergic neurons projecting from substantia nigra to striatum are severely affected in the early stage of Parkinson's disease (PD), with axonal degeneration preceding the loss of cell bodies. Our previous st...
Axons of dopaminergic neurons projecting from substantia nigra to striatum are severely affected in the early stage of Parkinson's disease (PD), with axonal degeneration preceding the loss of cell bodies. Our previous study indicated that the dysfunctional retrograde axonal transport could lead to the death of dopaminergic neurons resulting in PD (10.1111/j.1471-4159.2008.05526.x). However, dynein, as the main molecule involved in retrograde axonal transport, was not affected. This study aimed to verify the hypothesis that dynactin rather than dynein may be one of the key factors in the retrograde degeneration of dopaminergic neurons in the early stage of PD. Dynactin morpholino was used to inhibit the expression of dynactin in transgenic (Vmat2:GFP) zebrafish, resulting in a significant decrease of diencephalon dopamine neurons and synuclein aggregation in the basal plate region. In the dopaminergic SH-SY5Y cell line, dynactin-siRNA knockdown resulted in the expression of dynein shifting from dispersed distribution to concentration in synapses and cytoplasm near axons, and the fusion rate of dynein to dynactin was decreased, especially in axons, which blocked the retrograde axonal transport of α-synuclein and autophagy flow. Our results linked the knockdown of dynactin gene to the dysfunction of axonal microtubule transport system, suggesting that dynactin may be one of the key factors contributing to the retrograde degeneration of dopaminergic neurons in the early stage of PD.
Saccharomyces boulardii supplementation does not affect anaerobic power gain induced by short-term sprint interval training in physically active individuals.
Hudson ASR, Lisboa AMT, Andrade PVR … +5 more , Bruzzi RS, Martins YAT, Soares DD, Martins FS, Wanner SP
Braz J Med Biol Res · 2025 · PMID 40136227 · Publisher ↗
Sprint interval training (SIT), which consists of vigorous-intensity exercise interspersed with periods of rest or low-intensity exercise, can improve human anaerobic performance. Probiotic strains, including yeasts (e.g...
Sprint interval training (SIT), which consists of vigorous-intensity exercise interspersed with periods of rest or low-intensity exercise, can improve human anaerobic performance. Probiotic strains, including yeasts (e.g. Saccharomyces boulardii; Sb), have beneficial effects on human health; however, evidence regarding the effects of probiotics on anaerobic performance is unavailable. The current study investigated whether Sb supplementation influences the SIT-induced changes to the following performance variables: peak (PPO) and mean (MPO) power output. Fifteen healthy individuals (twelve men and three women) were randomly divided into two groups: placebo (PLA; n=8) and Sb (n=7). The individuals performed six SIT sessions on a cycle ergometer (four to seven 30-s all-out sprints thrice weekly). During the training period, participants ingested a capsule containing PLA or at least 1×109 Sb cells daily for 14 days. Performance-related variables were compared between the first and last training sessions. Sb supplementation did not influence the changes in PPO and MPO across the two weeks of training (P>0.05); therefore, the data from both groups were analyzed collectively to assess performance changes induced by SIT. Training increased PPO, an index of anaerobic power, in the sixth session compared to the first session (by 8±11% in the first sprint; +1.0±1.2 W/kg; P=0.008) but did not change MPO. In conclusion, short-term SIT improved the participants' anaerobic performance (power), as evidenced by increased PPO. Sb supplementation did not affect the improved anaerobic power caused by SIT.
The extent of carbapenem-resistant encoding genes in Klebsiella pneumoniae from COVID-19 and non-COVID-19 patients in a tertiary care center, Saudi Arabia.
Al Bshabshe A, Hamid ME, Salem E … +5 more , Abdelrahim IM, Assiry M, Alasmari A, Joseph M, Alhammdi Y
Braz J Med Biol Res · 2025 · PMID 40136226 · Publisher ↗
Rapid dissemination of Klebsiella pneumoniae carbapenemase (KPC) is a leading cause of treatment failure, significantly increasing morbidity and mortality rates among inpatients, particularly in the intensive care unit (...
Rapid dissemination of Klebsiella pneumoniae carbapenemase (KPC) is a leading cause of treatment failure, significantly increasing morbidity and mortality rates among inpatients, particularly in the intensive care unit (ICU). This study aimed to detect the occurrence of carbapenemase- and carbapenem-resistant-encoding genes in K. pneumoniae isolates from COVID-19 positive and negative patients, and to assess their impact on patient outcomes. A prospective analysis was conducted at a tertiary care hospital in Saudi Arabia, collecting 97 carbapenem-resistant K. pneumoniae (CRKP) isolates from patients with COVID-19 during 2020-2021. Isolates were obtained from various clinical specimens. Antimicrobial susceptibility assays were performed using the Automated Vitek-2 system, and data were analyzed using IBM SPSS Statistics. The predominant carbapenemases identified were Oxacillinase-48 (OXA-48), followed by KPC and New Delhi metallo-β-lactamase (NDM), with Imipenemase (IMP) and Verona integron-encoded metallo-β-lactamase (VIM) being the least prevalent. COVID-19 did not significantly affect the distribution of these genes (P>0.05); however, COVID-19 status and age over 60 years significantly impacted the outcomes of CRKP patients. Other factors such as gender, total ICU or ward stay, and comorbidities did not significantly affect CRKP infection outcomes. The most common carbapenem-resistant genes identified were blaKPC, blaNDM, and blaOXA-48; however, they were not significantly associated with increased mortality.
Prevalence of invasive yeast infections in a COVID-19 intensive care unit in northeastern Brazil.
Medeiros SMFRS, Costa-Júnior SD, Perez VP … +6 more , Sousa ESS, Campana EH, Araújo MAO, Guerra FQS, Dejani NN, Souto FO
Braz J Med Biol Res · 2025 · PMID 40136225 · Publisher ↗
The COVID-19 pandemic has caused a global crisis, overwhelming hospitals and intensive care units (ICU) and leading to an increase in nosocomial infections due to prolonged hospitalization and other risk factors. The pre...
The COVID-19 pandemic has caused a global crisis, overwhelming hospitals and intensive care units (ICU) and leading to an increase in nosocomial infections due to prolonged hospitalization and other risk factors. The present study evaluated the prevalence of secondary fungal infections in critically ill patients with COVID-19. This is a retrospective, single-center study conducted in a hospital in northeastern Brazil, which evaluated 1,364 medical records of patients admitted to a COVID-19 ICU during 2020 and 2021. A total of 327 pathogenic yeasts were isolated from 132 (40.4%) respiratory, 70 (21.4%) blood, 124 (37.9%) urine, and one (0.3%) surgical wound samples. Fungal infections were diagnosed in the intermediate (5 to 12 days) or late (≥12 days) stage of hospitalization. The most frequent yeast isolated from critically ill COVID-19 patients was Candida albicans [126 (67.7%) and 60 (42.6%)], followed by Candida tropicalis [25 (13.4%) and 39 (27.7%)]. Candida parapsilosis isolates increased 5.7-fold in 2021 [40 (28.4%)] compared to 2020 [7 (3.8%)]. The least frequently isolated in 2020 and 2021 were Nakaseomyces glabratus [4 (2.2%) and 1 (0.7%)], and Pichia kudriavzevii, which was isolated only in 2021 (1 (0.7%)). During the study period, a decrease in susceptibility to antifungals was observed: susceptibility to voriconazole reduced from 100 to 77.2%, to flucytosine from 99.4 to 78.8%, and to micafungin from 99.4 to 83.6%. The changes in the frequency of species causing secondary infections in critically ill COVID-19 patients and susceptibility to the antifungals indicate the need for early and adequate diagnosis to minimize negative outcomes.
Coptisine ameliorates colitis in mice by modulating cPLA2/TRPM8/CGRP-1 signaling pathways and strengthening intestinal barrier function.
Wu W, Shu C, Chen L … +5 more , Wei S, Jing M, Li H, Li H, Zhao Y
Braz J Med Biol Res · 2025 · PMID 40053041 · Full text
Coptisine (COP), a naturally occurring alkaloid, is recognized for its varied pharmacological impacts and its supportive function in intestinal well-being. However, the role of COP to protect the colonic epithelium in co...
Coptisine (COP), a naturally occurring alkaloid, is recognized for its varied pharmacological impacts and its supportive function in intestinal well-being. However, the role of COP to protect the colonic epithelium in colitis has not been extensively investigated. The objective of this study was to assess the efficacy of COP in ameliorating colitis by investigating intestinal histopathology, mucosal barrier function, and transient receptor potential (TRP) signaling pathways in mice with colon disease compared to a control group, thereby elucidating the underlying mechanisms of its action. The results demonstrated a marked improvement in diarrhea and bleeding, an improvement in general behavioral competencies of the mice, and a decrease in disease activity index (DAI) scores. Histopathological analysis indicated a reduction in intestinal inflammation and an enhancement of intestinal mucosal barrier function. Our research identified that the protein expressions of the TRP family including transient receptor potential cation subfamily M member 8 (TRPM8), transient receptor potential vanilloid 1 (TRPV1), and transient receptor potential ankyrin 1 (TRPA1) were significantly upregulated with COP treatment. Compared with the model, COP markedly downregulated cytosolic phospholipase A2 (cPLA2) levels, while upregulating calcitonin gene-related peptide-1 (CGRP-1) protein expressions. Our study revealed that COP enhanced intestinal barrier function by modulating the cPLA2/TRPM8/CGRP-1 signaling pathway, thus shedding light on the mechanism by which COP mitigates inflammation in the intestinal mucosa. These findings provided new insights on COP as a therapeutic agent in ulcerative colitis (UC).
Isokinetic assessment of muscle function according to physical activity level and cardiovascular risk in asymptomatic adults aged 20 to 80 years.
Dourado VZ, Nascimento MB, Navarro RC … +6 more , Silva RPD, Gonze BB, Guedes KM, Lauria VT, Vieira WO, Ostolin TLVDP
Braz J Med Biol Res · 2025 · PMID 40053040 · Full text
As limb muscle function is age- and sex-related, both elbow and knee isokinetic muscle functions and their main predictors, such as physical activity level and cardiovascular risk factors, should be determined. We aimed...
As limb muscle function is age- and sex-related, both elbow and knee isokinetic muscle functions and their main predictors, such as physical activity level and cardiovascular risk factors, should be determined. We aimed to describe the percentiles of normality of the isokinetic muscle function of the knee and elbow joints. Secondarily, we developed equations to predict muscle function in apparently healthy adults aged 20-80 years, including cardiovascular risk factors. We conducted a cross-sectional study with 1,334 adults. We collected sociodemographic data, self-reported cardiovascular risk, anthropometry, body composition (bioelectrical impedance), moderate-to-vigorous physical activity (MVPA) (triaxial accelerometry), and isokinetic muscle function. Multiple regression analysis was used to develop equations to predict isokinetic muscle function. Percentiles of normality for muscle function were described by sex and age (20-39, 40-59, and >60 years). The models accounted for 49.6-70.9% of the total variability of muscle function, but MVPA and cardiovascular risk slightly influenced the coefficient of determination (additional ΔR2=0.003-0.006). Demographic and anthropometric variables were more relevant predictors of isokinetic muscle function (R2=0.50-0.70) than MVPA and cardiovascular risk. Even though they correlated with muscle function, cardiovascular risk and MVPA failed to explain the variability of muscle function largely determined by anthropometric and sociodemographic data. The percentile values and equations developed will help in interpreting the isokinetic muscle function and improve its clinical use.
Effects of physical exercise on the lipid profile of perimenopausal and postmenopausal women: a systematic review and meta-analysis.
Bernal JVM, Sánchez-Delgado JC, Jácome-Hortúa AM … +4 more , Veiga AC, Andrade GV, Rodrigues MR, Souza HCD
Braz J Med Biol Res · 2025 · PMID 40053039 · Full text
During the climacteric period, the decline in ovarian hormones leads to changes in the lipid profile. Physical exercise is the main non-pharmacological recommendation for controlling lipid levels. However, the effects on...
During the climacteric period, the decline in ovarian hormones leads to changes in the lipid profile. Physical exercise is the main non-pharmacological recommendation for controlling lipid levels. However, the effects on the lipid profile in perimenopausal and postmenopausal women are incipient and inconclusive. In this context, we searched the Embase, PubMed, Scopus, and Web of Science databases for randomized clinical trials on the effects of exercise on the lipid profile of these women. We excluded studies that did not specify criteria for classifying the climacteric phase, that involved women undergoing hormone replacement therapy, or that examined combined treatments or acute effects of physical exercise. The meta-analysis indicated that general physical exercise increased high-density lipoprotein cholesterol (HDL-C) levels (mean difference [MD]=4.89; 95% confidence interval [95%CI]=0.97 to 8.81) in perimenopausal women. For obese postmenopausal women, 16 weeks of aerobic training increased HDL-C levels (MD=3.88; 95%CI=0.56 to 7.20) and reduced total cholesterol (MD=-22.36; 95%CI=-29.67 to -15.05) and low-density lipoprotein cholesterol (LDL-C) levels (MD=-17.86; 95%CI=-25.97 to -9.75), whereas 12 weeks of resistance training increased HDL-C levels (MD=4.20; 95%CI=1.16 to 7.23) and decreased triglycerides (MD=-14.86; 95%CI=-26.62 to -3.09) and LDL-C levels (MD=-16.36; 95%CI=-28.05 to -4.67). Overall, the results showed that physical exercise regulated lipid profiles in perimenopausal and postmenopausal women. Specifically, 12 weeks of resistance exercise and 16 weeks of aerobic exercise improved the lipid profile of obese postmenopausal women.
Rac1 overexpression promotes Treg-derived cytokines to mediate choroidal neovascularization in wet age-related macular degeneration.
Li J, Ren Y, Li H … +1 more , Zheng Z
Braz J Med Biol Res · 2025 · PMID 40053038 · Full text
Age-related macular degeneration (AMD), particularly the wet form characterized by choroidal neovascularization, is a leading cause of vision loss. Dysregulation of regulatory T cells (Tregs), key modulators of inflammat...
Age-related macular degeneration (AMD), particularly the wet form characterized by choroidal neovascularization, is a leading cause of vision loss. Dysregulation of regulatory T cells (Tregs), key modulators of inflammatory responses, may contribute to wet AMD pathogenesis. This study explored the involvement of Tregs and the Rac1 signaling pathway in modulating Treg-derived cytokine expression and their role in choroidal neovascularization during wet AMD progression. Peripheral blood samples from healthy controls, dry AMD patients, and wet AMD patients were collected. An in vitro transmembrane co-culture system of Tregs and human choroidal endothelial cells (HCECs) was employed to investigate the impact of Tregs (with or without Rac1 silencing) on the angiogenic phenotype of HCECs. A mouse model of AMD was established to evaluate the effects of a Rac1 inhibitor and IL-10/TGF-β neutralization on Tregs and choroidal neovascularization. An increased Treg percentage in the CD4+ T lymphocyte population was found in the peripheral blood samples of wet AMD patients. Tregs from wet AMD patients showed an increased expression of Rac1 and an elevated production of IL-10 and TGF-β1. Rac1 silencing suppressed Treg stability and differentiation, and impaired the pro-angiogenic effect of Tregs on HCECs. In the animal model of AMD, the administration of a Rac1 inhibitor or neutralizing antibodies against IL-10/TGF-β1 reduced Treg abundance and attenuated choroidal neovascularization. Rac1 upregulation in Tregs promoted IL-10 and TGF-β1 production to mediate choroidal neovascularization in wet AMD. Targeting Rac1 and Treg-derived IL-10/TGF-β1 production in Tregs may serve as a strategy to ameliorate AMD progression.
Quantifying lactulose and mannitol using LC-MS/MS in a clinical study of children with environmental enteric disease.
Magalhães LMVC, Rodrigues FAP, Filho JQ … +9 more , Gondim RNDG, Ribeiro SA, Rôla TBM, Clementino MAF, Maciel BLL, Magalhães PJC, Havt A, Santos AA, Lima AAM
Braz J Med Biol Res · 2025 · PMID 40053037 · Full text
Dysfunction of the intestinal epithelium barrier (DIEB) is frequent and can lead to serious complications in early childhood when diagnosis and clinical intervention are limited, especially in children with environmental...
Dysfunction of the intestinal epithelium barrier (DIEB) is frequent and can lead to serious complications in early childhood when diagnosis and clinical intervention are limited, especially in children with environmental enteric disease and malnutrition. The use of refined analytical techniques is increasingly necessary in this context. This study aimed to validate the high-performance liquid chromatography method coupled with tandem mass spectrometry (LC-MS/MS) to measure DIEB by lactulose:mannitol ratio detection (LM test) in samples of children with different social profiles from Fortaleza, Ceará. The first experimental set was conducted to validate the method through laboratory parameters, such as limit of detection (LD), limit of quantification (LQ), specificity/selectivity, linearity, accuracy, and precision. All validation parameters achieved detection and recovery standards within an acceptable coefficient of variation. Community samples (human development index (HDI) from 0.000 to ≤0.499) were obtained from children from the cohort study Malnutrition-Enteric Diseases, Fortaleza-CE (environmental enteric disease; EED group). The control group samples came from a school located in a region with a high HDI (>0.8). Mannitol excretion was lower in the EED group than in the control group (P<0.0001). On the other hand, LM was higher in this group compared to the control group (P<0.0001). For the first time, a robust analytical approach was used to detect biomarkers of environmental enteropathy (LM) in community samples, confirming with high-sensitivity the damage to the intestinal epithelial barrier function in populations living in low socio-economic conditions.
1α,25-Dihydroxyvitamin D3 accelerates skin wound re-epithelialization by promoting epidermal stem cell proliferation and differentiation through PI3K activation: an in vitro and in vivo study.
Yan R, Liu Z, Wang S … +1 more , Fan D
Braz J Med Biol Res · 2025 · PMID 40053036 · Full text
1α,25-Dihydroxyvitamin D3 (VD3), the active form of vitamin D, plays a crucial role in wound healing. In this study, we aimed to investigate the effect of VD3 on the proliferation and differentiation of epidermal stem ce...
1α,25-Dihydroxyvitamin D3 (VD3), the active form of vitamin D, plays a crucial role in wound healing. In this study, we aimed to investigate the effect of VD3 on the proliferation and differentiation of epidermal stem cells (EpSCs) and monitor its impact on re-epithelialization. We established a murine full-thickness skin defect model and applied four doses of VD3 (0, 5, 50, and 250 ng/mouse/day) to the wounds topically for three days. Immunostaining and flow cytometry confirmed the effect of VD3 on the proliferation and differentiation of EpSCs in wounds. This effect of VD3 (0, 1, 10, and 50 nM) on EpSCs and its possible mechanism were further confirmed in vitro by CCK8, westen blot, immunostaining, and flow cytometry. We found that on day five post-wounding, the means±SD length of the neo-epidermis was 195.88±11.57, 231.84±16.45, 385.80±17.50, and 268.00±8.22 μm in the control, 5, 50, and 250 ng groups, respectively, with a significant difference from the control (all P<0.05). Immunostaining and flow cytometry showed that VD3 improved the proliferation and differentiation of K15+ EpSC (vs control, all P<0.05), K14+ epidermal progenitor cells (vs control, all P<0.05), and K10+ epidermal terminal cells (vs control, all P<0.05) in vivo and in vitro. The PI3K signaling pathway appeared to underlie this response because significant inhibition of the response was found when inhibitors were used to inhibit PI3K. Our study demonstrated that VD3 is a potent promoter of cutaneous wound healing by stimulating EpSC proliferation and differentiation through PI3K activation.
A U-shaped relationship between sleep duration and tinnitus incidence: analysis of 13,871 participants from NHANES.
Li Y, Peng L, Lan Y … +3 more , Hou T, Pan X, Yin S
Braz J Med Biol Res · 2025 · PMID 40053035 · Full text
Sleep duration is associated to various health impairments, while its comprehensive association with tinnitus is rarely investigated. The current study aimed to explore the relationship between sleep duration and tinnitu...
Sleep duration is associated to various health impairments, while its comprehensive association with tinnitus is rarely investigated. The current study aimed to explore the relationship between sleep duration and tinnitus incidence, and to determine the optimal sleep duration relating to the lowest tinnitus risk. Data of participants from the National Health and Nutrition Examination Survey (NHANES) from 2005 to 2012 and 2015 to 2018 were retrieved. A total of 13,871 participants were eligible and included in the analysis. Generally, sleep duration was lower in participants with tinnitus compared to those without (7.15±1.76 vs 7.30±1.51 h, P<0.001). After adjustment by demographics, lifestyle, and chronic diseases, a U-shaped relationship between sleep duration and tinnitus incidence was observed, with the inflection point at 8.5 h. Interestingly, in participants with sleep duration <8.5 h, sleep duration exhibited an independent negative correlation with tinnitus risk [OR=0.88 (95%CI: 0.84-0.93), P<0.001], while in participants with sleep duration ≥8.5 h, sleep duration had an independent positive association with tinnitus risk [OR=1.16 (95%CI: 1.04-1.28), P=0.006]. In conclusion, a U-shaped relationship was found between sleep duration and tinnitus incidence, with a sleep duration of about 8.5 h being associated with the lowest tinnitus risk.
Pregnant women with periodontal disease: can complete blood count be useful?
Sá PCS, Godoi APN, Bernardes GCS … +4 more , Almeida NA, Nogueira LS, Carvalho MG, Barros-Pinheiro M
Braz J Med Biol Res · 2025 · PMID 40053034 · Full text
Prenatal care is of fundamental importance and must be carried out by a multidisciplinary healthcare team, including dental care, as several changes and complications affecting the oral cavity may occur during pregnancy....
Prenatal care is of fundamental importance and must be carried out by a multidisciplinary healthcare team, including dental care, as several changes and complications affecting the oral cavity may occur during pregnancy. This was a cross-sectional study that aimed to analyze the hematological profile of pregnant women with and without periodontal disease (PD). Data were obtained by consulting medical and dental records, which were stratified into two subgroups: pregnant women with PD (n=107) and pregnant women without PD (n=42). Study variables were related to PD, sociodemographic, clinical, and laboratory characteristics. Data were collected from the complete blood count and the following indices were calculated: neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), derived NLR (dNLR), systemic inflammation response index (SIRI), aggregate index of systemic inflammation (AISI), and systemic immune-inflammation index (SII). The mean age in both subgroups was 27 years. Pregnant women with less education had more PD. Mean corpuscular volume was significantly higher in pregnant women with PD, probably a reflection of folate deficiency. White blood cell and lymphocyte counts were significantly higher in pregnant women with periodontitis, possibly reflecting an inflammatory process caused by bacterial invasion of the periodontium with systemic repercussions. This study reinforces the need for a multidisciplinary team, including a dentist, in prenatal care, to lower the risk of complications for the mother and child.
Factors associated with depression, anxiety, stress, PTSD, and fatigue of medical staff during the COVID-19 pandemic in Shanghai: a two-phase cross-sectional study.
Li Y, Wang X, Li M … +6 more , Hu B, Cheng J, Chen H, Li X, Zhu S, Li M
Braz J Med Biol Res · 2025 · PMID 40053033 · Full text
During the COVID-19 pandemic in Shanghai, medical workers were more vulnerable to psychological problems. This two-phase cross-sectional survey was conducted by online questionnaires to investigate the symptoms of depres...
During the COVID-19 pandemic in Shanghai, medical workers were more vulnerable to psychological problems. This two-phase cross-sectional survey was conducted by online questionnaires to investigate the symptoms of depression, anxiety, stress, post-traumatic stress disorder (PTSD), and fatigue in healthcare workers during the outbreak of COVID-19 and after the resumption of work and production in Shanghai. The questionnaire included the Depression Anxiety Stress Scale-21 (DASS-21), the Impact of Event Scale-Revised (IES-R), and the Fatigue Assessment Instrument (FAI). In Phase I (n=2192), the prevalence of depression, anxiety, stress, and PTSD symptoms among medical staff was 45.48, 41.93, 20.35, and 75.55%. In Phase II (n=1031), after work resumed in Shanghai, the prevalence was 19.79, 21.44, 28.23, and 12.22%, respectively. Fatigue had a mean score of 121.23±45.776 in Phase I and 144.73±44.141 in Phase II. Binary logistic regression identified risk factors associated with this psychological status: personal and familial chronic disease history; occupation, including doctor, nurse, or administrative staff; working in the fever clinic, infectious disease department, emergency or intensive care unit, hemodialysis room, or clinical laboratory; work experience of 3-6 years or 7-10 years; and involvement in nucleic acid sampling team. Medical staff self-reported comparatively high rates of depression, anxiety, stress, and, especially, PTSD symptoms during the COVID-19 pandemic in Shanghai. Our study indicated that after work resumption in Shanghai, it appeared that the overall mental health of medical staff improved somewhat. Nevertheless, the high level of fatigue exhibited still cannot be ignored.
The role of the PKCζ/JNK signaling pathway in regulating the development of femoral head necrosis.
Hu M, Li C, Sun Q … +5 more , Hu B, Yang J, Wang X, Huang J, Shen D
Braz J Med Biol Res · 2025 · PMID 40053032 · Full text
Osteonecrosis of the femoral head (ONFH) is a debilitating condition characterized by the death of bone cells in the hip joint, resulting in profound disability. This condition has a significant global prevalence. Glucoc...
Osteonecrosis of the femoral head (ONFH) is a debilitating condition characterized by the death of bone cells in the hip joint, resulting in profound disability. This condition has a significant global prevalence. Glucocorticoid (GC)-induced apoptosis of bone cells serves as a crucial cellular mechanism underlying ONFH. The protein kinase C zeta (PKCζ) and c-Jun N-terminal kinase (JNK)/c-Jun cascades have been implicated in the progression of ONFH, yet their interrelationship and contributions to disease development remain unclear. The objective of this study was to investigate the combined impact of PKCζ and JNK/c-Jun signaling on dexamethasone (Dex)-induced apoptosis in osteoblasts in vitro and in GC-induced ONFH rat models in vivo. In vitro experiments were conducted using hFOB1.19 osteoblastic cells to scrutinize the effects of Dex-induced apoptosis. The role of the PKCζ/JNK/c-Jun signaling pathway in this process was examined using naringenin-7-O-β-D-Glucuronide (N7G), a PKC inhibitor, and anisomycin, a JNK activator. The findings were further validated using a rat model of ONFH in vivo. Our results revealed that PKCζ activation augmented JNK/c-Jun signaling and facilitated Dex-induced osteoblast apoptosis. Inhibition of PKCζ with N7G mitigated these effects, while JNK activation with anisomycin intensified them. Similar regulatory effects on osteoblast apoptosis and ONFH progression were observed in the in vivo rat models. Glucocorticoids can induce osteoblast apoptosis and contribute to the development of ONFH by activating the PKCζ/JNK/c-Jun signaling pathway. This study provides compelling evidence supporting the potential therapeutic value of comprehending the pathogenesis of ONFH and developing targeted treatments for this debilitating condition.
Prediction of maximum oxygen uptake over time in adults: analysis from the FRIEND registry.
Dourado VZ, Barbosa AC, Simões MSMP … +10 more , Lauria VT, Matheus AC, Sadarangani KP, Arantes RL, Romiti M, Peterman JE, Arena R, Harber MP, Myers J, Kaminsky LA
Braz J Med Biol Res · 2025 · PMID 40053031 · Full text
Maximum oxygen uptake (V̇O2max) equations from developed countries are inaccurate for developing countries. Accordingly, we aimed to develop equations to predict treadmill V̇O2max over time based on variables other than...
Maximum oxygen uptake (V̇O2max) equations from developed countries are inaccurate for developing countries. Accordingly, we aimed to develop equations to predict treadmill V̇O2max over time based on variables other than exercise test in adults from the USA and Brazil undergoing cardiopulmonary exercise testing (CPET). We analyzed data from 2,170 adults who underwent two CPETs (1,307 men; 20-85 years) from the USA (n=1,880) and Brazil (n=290) with a second test after 2.0±1.7 years on average. We fit linear mixed-effects models to develop equations using 90% of the sample, randomly selected. In the remaining 10% of the cohort, we used the coefficient of variation, intraclass correlation coefficient, and the Bland and Altman plots to cross-validate the optimal equation. Our best linear mixed model equation was as follows: V̇O2max (mLO2·kg-1·min-1) = 62.01 - (0.23×Ageyears) - (0.001×Age×Age) - (0.65×Body mass indexkg/m 2) + (5.47×Sexfemales=0; males=1) + (2.78×CountryBrazil=0; USA=1) - (0.68×Arterial hypertensionno=0; yes=1) - (0.45×Hyperlipidemiano=0; yes=1) - (2.02×Smokingno=0; yes=1) - (4.36×Insufficiently activeno=0; yes=1) - (1.67×Beta-blockersno=0; yes=1); R2=0.566. Our main equation was reliable at baseline according to Bland and Altman plot results (mean difference, 0.01 mLO2·kg-1·min-1: 95%CI, -13.94 to 13.98; P=0.966) and over time (0.44 mLO2·kg-1·min-1: 95%CI, -13.5 to 12.4; P=0.439). Demographic and anthropometric attributes, cardiovascular risk, and beta-blockers are valuable for predicting V̇O2max at baseline and over time. The developed equations may apply to countries with socioeconomic and demographic characteristics such as Brazil and the USA.
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