The effects of nicotinamide mononucleotide (NMN) on streptozotocin (STZ)-induced islet β-cell dysfunction and the underlying mechanisms have not been fully elucidated. This study investigated the ameliorative effect and mechanism of NMN on islet β-cell dysfunction. NMN significantly increased the INS-1 cell viability following treatment with either STZ or erastin and effectively mitigated STZ-induced cell injury. Upon exposure to STZ, INS-1 cells exhibited significantly elevated intracellular Fe2+ levels, significantly increased reactive oxygen species (ROS) levels, and significantly decreased in the activities of superoxide dismutase (SOD) and glutathione (GSH). The levels of lipid peroxidation (LPO) and malondialdehyde (MDA) were substantially increased, and the mitochondrial membrane potential significantly decreased. Transmission electron microscopy further revealed mitochondrial shrinkage, rupture of the mitochondrial membrane, and disintegration of mitochondrial cristae. NMN markedly reduced intracellular iron accumulation in INS-1 cells treated with STZ. NMN subsequently attenuated intracellular ROS, LPO, and MDA levels while restoring GSH and SOD activities in STZ-exposed cells. Moreover, NMN restored the mitochondrial membrane potential and reversed the STZ-induced pathological changes in mitochondrial morphology. Compared with STZ treatment, ferrostatin-1 treatment significantly upregulated Nrf2 and GPX4 expression. In contrast, compared with STZ treatment, erastin treatment suppressed Nrf2 and GPX4 expression. Notably, compared with STZ or erastin treatment, cotreatment with NMN resulted in a further reduction in Keap1 expression and a significant upregulation of Nrf2 and GPX4. NMN may alleviate STZ-induced INS-1 cell ferroptosis by activating the Nrf2/GPX4 pathway, providing a theoretical basis for the treatment of diabetes mellitus.
Intracerebral hemorrhage (ICH) is a hemorrhagic stroke causing severe secondary brain injury. Acupuncture has been shown to be effective in treating ICH, but the mechanism remains unclear. ICH was induced by injection of autologous blood, followed by acupuncture treatment at Baihui (DU20) and Qubin (GB7) acupoints. Histopathological results showed that acupuncture inhibited ICH-induced neuronal apoptosis and oxidative stress in perihematomal areas. Importantly, molecular and pathological findings proved that acupuncture stimulation significantly induced the Lung-Kruppel-like factor (LKLF) expression in perihematomal tissues of ICH-induced rats. The embryonic day 18 (E18) rat primary cortical neurons were treated with hemin as an in vitro model, and LKLF was overexpressed using lentiviral vectors to ascertain its function. LKLF overexpression inhibited neuronal apoptosis and oxidative stress and mitigated mitochondrial injury evidenced by decreased mitochondrial membrane potential in hemin-induced neurons. Both in vivo and in vitro experiments showed that mitofusin2 (Mfn2) expression was inhibited in neurons but increased upon acupuncture and LKLF overexpression. This suggested that the remission of ICH injury via acupuncture or LKLF overexpression might be related to the upregulation of Mfn2 reactivity. Dual luciferase assay demonstrated that LKLF activated Mfn2 promoter activity, showing that LKLF might improve mitochondrial function through transcriptional activation of Mfn2 expression, which subsequently mitigated hemin-induced neuronal injury. The rescue experiments in vivo indicated that LKLF knockdown suppressed Mfn2 expression and counteracted the attenuation of acupuncture on ICH-induced neuronal injury. These findings suggested that acupuncture might activate the LKLF/Mfn2 pathway, therefore inhibiting oxidative stress and neuronal apoptosis in ICH-induced rats.
Obesity has emerged as a critical factor influencing host-pathogen interactions and infection outcomes. However, its role in protozoan infections such as giardiasis remains poorly understood. In this study, we investigated the effects of a high-calorie, high-fat diet on metabolic, intestinal, and immune parameters in gerbils infected with Giardia lamblia. Our results demonstrated that the high-fat diet significantly increased body weight and induced metabolic disturbances, including dyslipidemia, hepatic fat accumulation, and altered adipokine production. Moreover, Giardia infection exacerbated these effects, leading to intensified intestinal inflammation and epithelial damage. Notably, obese animals exhibited a compromised immune response to infection, characterized by reduced production of inflammatory cytokines and increased parasitic load after two weeks. These findings indicated that obesity weakened the immune system's ability to control Giardia infection, thereby exacerbating the severity of giardiasis. Additionally, the combination of obesity and infection resulted in morphological alterations in intestinal tissue, further amplifying inflammation and impairing immune responses. Our study underscores the importance of obesity management to mitigate the inflammatory state that worsens infectious diseases, such as giardiasis. This is particularly relevant in vulnerable populations, such as children, who are at higher risk of infection and its associated complications.
Dementia is a growing global health challenge driven by population aging and unequal exposure to biological, behavioral, social, and environmental determinants across the life course. Existing evidence demonstrates that these factors accumulate and interact from fetal development through old age, shaping cognitive reserve, brain resilience, and vulnerability to neurodegeneration. However, current models rarely integrate these multilevel influences in a structured manner. This study proposes a comprehensive multilevel conceptual framework for dementia that maps determinants across seven levels (biological, behavioral, psychological, individual, family, community, and national) and across all life stages, from prenatal development to late life. The framework is organized along a bi-axial structure that aligns levels of influence with temporal windows of exposure, allowing a clear visualization of how early-life and midlife factors contribute to dementia in older age. Two illustrative pathways are explored in depth. The first describes the development of cognitive reserve, highlighting the roles of maternal health, education, health literacy, social engagement, and lifelong learning in delaying symptom onset despite neuropathological burden. The second focuses on cerebrovascular integrity, demonstrating how prenatal vascular development, lifestyle behaviors, and cardiovascular risk profiles influence vascular cognitive impairment and interact with Alzheimer-related pathologies. The framework distinguishes modifiable population-level determinants, such as education quality and public health policies, from more fixed biological factors, thereby identifying critical intervention points. By integrating life-course epidemiology with multilevel determinants, this model provides a structured approach for understanding dementia etiology and supports the development of targeted prevention strategies across individual, community, and societal domains.
Refeeding syndrome (RS) encompasses electrolyte and metabolic disturbances, and its incidence depends on diagnostic criteria. We aimed to evaluate the incidence and risk factors for RS in inpatients at a university hospital in Brazil, who received enteral or parenteral nutrition. This retrospective study included all patients admitted to the hospital who received enteral or parenteral feeding after at least a 3-day fasting period. RS diagnosis was based on phosphorus, potassium, and magnesium changes in the first 3 days after diet reintroduction. Clinical, anthropometric, and other laboratory evaluations, as well as caloric prescriptions, were also collected. Risk factors for RS development were evaluated using logistic regression, and the 30-day mortality risk associated with RS was analyzed using Cox regression. A total of 315 participants were included in the final analysis. The median age was 65 years, 55% were men, 45% had a diagnosis of cancer, and the body mass index was 23.7 (IQR: 20.5-27.0) kg/m2. Development of RS was found in 36.8%. The risks associated with RS development were female gender and higher serum phosphorus and sodium levels. The 30-day survival rates for patients with or without RS were 50.7 and 49.9%, respectively (P=0.42). In the Cox regression model, the diagnosis of RS was not associated with death risk (HR: 0.81, 95%CI: 0.54-1.21). In conclusion, a high incidence of RS was found, but this was not associated with increased death risk, which could be explained by the prompt diagnosis and correction of electrolyte deficits.
This study aimed to investigate the role of microglia and NOD-like receptor protein 3 (NLRP3) inflammasome-mediated neuroimmune pathways in the analgesic effects of electroacupuncture (EA) in a mouse model of Parkinson's disease (PD). Male C57BL/6 mice (8 weeks old) were randomly assigned to the control, PD model, and PD + EA groups. PD was induced by intraperitoneal injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), while control mice received saline. EA was administered to the motor cortex once daily for five consecutive days in the PD + EA group, whereas PD model mice were restrained without receiving EA stimulation. Behavioral assessments were performed to evaluate motor function and nociceptive sensitivity. Immunohistochemistry, immunofluorescence, and western blot analyses were used to quantify tyrosine hydroxylase (TH), ionized calcium-binding adapter molecule 1 (Iba-1), NLRP3 inflammasome components, and inflammatory cytokines in key brain regions. Compared with control mice, PD model mice showed reduced motor performance and heightened nociceptive sensitivity, accompanied by a decrease in TH-positive neurons and an increase in Iba-1-positive microglia in both the substantia nigra and amygdala. EA significantly improved motor performance and increased pain thresholds. Moreover, EA preserved TH-positive neurons, suppressed microglial activation, and downregulated the expression of NLRP3, ASC, caspase-1, interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α in the amygdala. These findings suggest that EA alleviates PD-related pain, possibly by modulating microglial activation and NLRP3 inflammasome signaling in the amygdala, thereby reducing neuroinflammation.
Among the morbidities triggered by obesity, metabolic dysfunction-associated steatotic liver disease (MASLD) stands out, with its progression resulting from the deposition of lipid molecules in the liver. There is a growing interest in natural/functional foods as an alternative for improving health, as well as for the treatment and prevention of diseases. Capsinoids (Cap) - bioactive compounds present in peppers of the genus Capsicum annuum - have been studied for promoting loss of adiposity and increased caloric expenditure. Therefore, this study aimed to investigate the effects of Cap on liver parameters in obese (Ob) rats induced by a high-fat diet (HFD). Male Wistar rats were initially randomized into two groups: standard diet (SD) and HFD. The protocol lasted 27 weeks, including 19 weeks of induction and maintenance of obesity and 8 weeks of Cap treatment. At week 19, the HFD rats were redistributed into the Obese (Ob) and Obese capsinoids (ObCap) groups, and the ObCap group was supplemented daily with chronic Cap treatment by orogastric gavage (10 mg Cap/kg daily). Cap treatment was not effective in improving adiposity and inflammatory parameters of obesity, although it reduced ghrelin, cholesterol, and hepatic fat accumulation, and attenuated MASLD progression, which may be promising for combating chronic diseases related to lipid metabolism.
The combination of drugs for malaria treatment holds promise, although the potential for drug-drug interactions remains insufficiently explored in novel therapeutic combinations. This study aims to assess these interactions using physiologically based pharmacokinetic modeling, supported by data-driven parameter optimization, as a step towards the preclinical development of a formulation containing chloroquine and colchicine. Given that both compounds share metabolic pathways involving CYP3A4 and CYP2D6, we developed individual and population models using a middle-out strategy in PK-Sim®, an open-source software, and validated these models by comparing predicted and observed pharmacokinetic parameters. Simulations evaluated competitive inhibition between the compounds. The results indicated no significant changes in systemic exposure, with the area under the curve and maximum concentration values remaining consistent between single and combined administration. Our findings suggest that the proposed modeling is a powerful tool for predicting pharmacokinetic interactions during the preformulation stage, offering mechanistic insight and supporting rational decision-making prior to in vivo studies. The absence of significant drug-drug interactions between chloroquine and colchicine reinforces the feasibility of advancing this combination in future therapeutic development.
Pancreatic adenocarcinoma (PAAD) is a highly aggressive and lethal malignancy originating from the epithelial cells lining the pancreatic ducts. To date, no robust biomarkers have been established to reliably predict PAAD prognosis. To identify potential transcriptional biomarkers, we analyzed transcription factor expression in PAAD patients from The Cancer Genome Atlas (TCGA) and identified ZNF821 as a novel prognostic marker. Higher ZNF821 expression was significantly associated with improved patient survival and was positively correlated with increased immune infiltration and cytotoxic activity within the tumor microenvironment. Additionally, elevated ZNF821 levels predicted a favorable response to immunotherapy. We further discovered that tumors downregulate ZNF821 through DNA methylation, facilitating immune evasion during tumor progression. To investigate its functional mechanisms, we analyzed proteins regulated by or interacting with ZNF821. Moreover, we identified existing drugs that may target ZNF821, suggesting potential therapeutic applications for PAAD. Experimental validation using RT-PCR confirmed ZNF821 downregulation in pancreatic cancer cell lines. Furthermore, tumor growth comparisons between ZNF821-overexpressing and ZNF821-null models demonstrated that ZNF821 enhances anti-tumor immunity, contributing to tumor suppression. In summary, our study identified ZNF821 as a novel prognostic biomarker in PAAD, offering new insights into tumor immune evasion and potential therapeutic strategies.
Curcumin inhibits osteoclastogenesis and mitigates osteoporosis. Our data demonstrated that curcumin decreases membrane-bound RANKL (mRANKL) levels on osteoblasts. Notably, mRANKL exerts a more prominent role in osteoclastogenesis than its soluble counterpart (sRANKL). This study aimed to explore the role of RANKL membrane localization in curcumin-regulated osteoclastogenesis. We primarily investigated the effect of curcumin on mRANKL expression in osteoblasts in vitro and in vivo. Using fluorescence-activated cell sorting (FACS) for RANKL and co-culture experiments of osteoclast precursors (OCPs) with osteoblasts, we further analyzed the association between curcumin's indirect inhibition of osteoclast differentiation and mRANKL production. Finally, we explored the involvement of matrix metalloproteinase 14 (MMP14) in curcumin-mediated regulation of mRANKL levels. The results showed that curcumin significantly reduced mRANKL expression in osteoblasts. Curcumin also abrogated the upregulated RANKL levels in osteoblasts of Tg-hRANKL transgenic mice. Co-culture assays revealed that curcumin exerted the weakest inhibitory effect on osteoclast differentiation when OCPs were co-cultured with mRANKL-negative osteoblasts. Additionally, curcumin increased MMP14 expression in osteoblasts and enhanced the MMP14-RANKL interaction. Importantly, silencing MMP14 in osteoblasts reversed curcumin-inhibited mRANKL levels and osteoclast differentiation. Collectively, our findings indicated that curcumin inhibited mRANKL production in osteoblasts, which contributes to its therapeutic effect on osteoclastic osteoporosis.
Aging is associated with the accumulation of oxidative damage. Isoliquiritigenin (ISL), a natural flavonoid, exhibits antioxidant properties, but its effect on lifespan and the underlying mechanisms remains incompletely understood. This study aimed to investigate whether ISL extends lifespan in Caenorhabditis elegans through the transcription factor DAF-16 and the aquaporin AQP-2. We employed lifespan assays, stress resistance tests, intracellular ROS measurement, osmotic water permeability assays in Xenopus oocytes, genetic manipulation (using mutants and RNAi), quantitative real-time PCR, and fluorescence microscopy to assess DAF-16 localization and target gene expression. ISL extended the mean lifespan of wild-type C. elegans by 15.35% at 20 μM (P<0.01). It enhanced resistance to oxidative stress (36.54% higher survival under paraquat) and heat shock (20.56% higher survival at 37°C), and reduced intracellular ROS levels. Mechanistically, ISL increased DAF-16 nuclear translocation by 44.3% (P=0.003), and upregulated the expression of its target genes, including sod-3 (3.2-fold, P=0.008) and aqp-2 (2.9-fold, P=0.012). ISL also increased the osmotic water permeability of Xenopus oocytes by 1.7-fold (P=0.007), and the effect was abolished by the aquaporin inhibitor HgCl2. Genetic ablation of aqp-2 nullified ISL-induced lifespan extension (P=0.65 vs control) and ROS reduction. Crucially, aqp-2 RNAi suppressed ISL-driven DAF-16 nuclear accumulation and sod-3 expression, establishing a feedforward loop. ISL extended lifespan and enhanced stress resistance in C. elegans by activating a DAF-16/AQP-2 regulatory module, thereby linking water homeostasis to the transcriptional control of aging.
Orofacial musculoskeletal pain (OMP) is a common feature of temporomandibular disorders (TMD), a group of conditions affecting the temporomandibular joint, chewing muscles, and associated structures. The etiology of muscular TMD is currently understood within a biopsychosocial model of pain, highlighting the complexity related to OMP. In this context, the objective of this study was to investigate the OMP induced by psychological/emotional stress (ES) in rats, regarding the role of the endocannabinoid system (ECS) through CB1 and CB2 receptors. Male Wistar rats were divided into Control and ES groups. OMP was induced by ES using the communication box model and evaluated through the mechanical threshold in masticatory muscles. c-Fos, CB1, and CB2 immunostaining was evaluated in the trigeminal ganglion (TG) and in the trigeminal nucleus caudalis (Sp5C). The selective CB1 or CB2 antagonist (AM251 or AM630, respectively) or the cannabinoid receptor non-selective agonist (WIN55,212-2) were administered to both groups, and the OMP was evaluated. The mechanical sensitivity of the masticatory muscles increased in the ES group, accompanied by increased c-Fos expression in the TG and Sp5C. AM251 and AM630 increased mechanical sensitivity, while WIN55,212-2 decreased the OMP. Furthermore, ES increased CB1 density in the TG and elevated both CB1 and CB2 in the Sp5C. Additionally, CB2 was increased in the masseter muscle. Thus, cannabinoid receptors played a protector role in OMP caused by ES, indicating that cannabinoid drugs or the modulation of the ECS may represent a promising approach for the treatment of OMP frequently observed in patients with TMD.
Despite growing evidence that nociceptive stimuli are processed and modulated by distinct neural mechanisms depending on biological sex and aging, these factors remain underrepresented in experimental and clinical pain research. Most preclinical studies continue to rely on young male rodents, overlooking potential differences in neuropathic pain perception between sexes and age groups. Understanding these variations is critical for advancing pain management strategies. Aged rats (22 months old) of both sexes were divided into three groups: orchiectomized (Orch) males, non-orchiectomized (Non-orch) males, and females. The animals underwent L5 spinal nerve ligation and were assessed for mechanical allodynia on the plantar surface of their left hind paw before nerve ligation and on days 7, 14, 21, and 28 post-ligation. By day 14, Non-orch males showed a significantly higher withdrawal threshold than Orch males, with an average difference of 8.46 g (P<0.005), which remained significant and increased over time, peaking at day 28, with 13.07 g (P<0.0006). By day 28, Non-orch males also showed greater mechanical allodynia than females, with an estimated mean difference of approximately 8 g (P=0.038). These findings suggest that male gonadal hormones mitigate neuropathic pain-induced mechanical allodynia. The study underscores the role of testosterone in pain modulation and highlights the need for further research on the interplay between hormonal regulation, aging, and neuropathic pain mechanisms.
One of the effects of the COVID-19 pandemic was the interruption of exercise programs for older adults, significantly impacting their physical performance (PP). Few studies have identified the effects of the interruption of exercise programs on the PP of older adults, and none have assessed the relationship between this outcome and objectively measured daily step count and sedentary behavior (SB). This study assessed the association between SB and daily step count with PP in 42 community-dwelling older adults (73.86±6.78 years old, 88.10% female) after an 18-month interruption of an exercise program due to the COVID-19 pandemic. SB and daily step count were measured using the activPAL3™ micro accelerometer, while PP was assessed through the 30-s sit-to-stand test, handgrip strength test, and Timed Up and Go (TUG) test. Data were analyzed using Pearson correlation test and linear regression model. Results showed that daily step count was significantly correlated with PP (r=0.38 to 0.42). Regression analysis revealed that a mean increment of 1,000 steps/day was associated with a mean increase of 0.31 repetitions in the sit-to-stand test, 0.89 kgF in handgrip strength, and a mean reduction of 0.30-s in TUG time. Additionally, older adults who reached approximately 9,325 steps/day demonstrated better PP outcomes compared to those who accumulated a lower number of daily steps. However, SB was not significantly associated with PP (P>0.05). These findings suggest that accumulating high amounts of daily steps may help mitigate declines in PP when structured exercise programs are interrupted.
Eosinophilic chronic rhinosinusitis (CRS), characterized by prominent eosinophil infiltration, has the highest postoperative recurrence rate among CRS subtypes. Given the critical role of eotaxins in CRS pathogenesis, this study aimed to identify eotaxins associated with eosinophilic CRS and evaluate their correlation with surgical outcomes. Transcriptomic data from GSE36830 revealed 125 differentially expressed genes (49 up-regulated, 76 down-regulated) in CRSwNP compared to CRSsNP, with significant enrichment of eosinophil and dendritic cell infiltration pathways. Functional analysis identified chemotaxis and cell migration as key dysregulated processes in CRSwNP. Among eotaxins, CCL26 and CCL13 emerged as hub molecules from the intersection of these dysregulated pathways. In a clinical cohort of 115 CRS patients, preoperative serum CCL26 and CCL13 levels were significantly elevated in CRSwNP compared to CRSsNP (P<0.001). ROC analysis demonstrated strong diagnostic power for nasal polyps (CCL26: AUC=0.895; CCL13: AUC=0.830). Higher preoperative CCL26 levels predicted poorer symptom improvement post-surgery (standardized β=−0.564, P<0.001). In conclusion, preoperative serum CCL26 serves as both a diagnostic biomarker for CRSwNP and a prognostic indicator for surgical outcomes, with elevated levels associated with reduced symptom improvement.
Respecting the patient's preferred place of death is a key indicator of the quality of palliative care. However, clinical factors may influence this outcome. This study aimed to compare the clinical profiles, symptom burden, and medical interventions of patients who died at home versus those who died in an inpatient setting (hospital) within the context of a Brazilian public healthcare institution. A retrospective study was conducted involving 227 patients who were followed by the Palliative Care Team at the Instituto de Assistência Médica ao Servidor Público Estadual (IAMSPE). Sociodemographic and clinical variables, symptom control, and pharmacological interventions were analyzed using generalized linear mixed models (GLMMs). Of these patients, 59.47% (n=135) died in the hospital ward and 40.53% (n=92) died at home. No statistically significant differences were observed between age or sex and place of death. Hospitalized patients presented with a greater number of symptoms, although no significant differences were found for pain and dyspnea. Most of the patients also had multiple metastases. The use of oxygen was significantly higher in the inpatient setting, while oral and enteral feeding was more feasible at home. Although the total number of medications administered was higher in the hospital, there were no significant differences in the use of morphine and midazolam between the groups. In conclusion, clinical severity was a key factor influencing hospitalization until death. Despite equivalent symptom control between settings, expanding access to structured home-based palliative care could enable patients to experience end-of-life care aligned with their preferences.
The introduction of combination antiretroviral therapy (cART) has significantly reduced AIDS-related morbidity and mortality. However, the prevalence of age-associated comorbidities, particularly cardiovascular diseases (CVD), has increased, becoming a leading cause of mortality in people living with HIV. This study investigated the interaction between cART regimens and dietary composition on electrocardiographic (ECG) parameters and myocardial histopathology. A total of 120 weanling Sprague Dawley rats were allocated to one of three diets for 15 weeks: normal chow, a calorie-dense low protein (CDLP) diet, or a calorie-dense normal protein (CDNP) diet. Each dietary group was then subdivided into four treatment groups for a further 9 weeks: a standard group (normal saline), Test group 1 (dolutegravir (DTG) plus tesamorelin), Test group 2 (DTG only), and a positive control (classical cART regimen). ECG recordings and histological assessments were performed at week 24. Significant intergroup variations in ECG indices were observed, including Q, R, S, and T wave amplitudes, PR interval, QRS duration, ST height, and QTc (all P < 0.0001). Myocardial fibrosis (P < 0.0001) was evident in animals from the TG2 (DTG only) and PC (classical regimen) groups maintained on CDLP and CDNP diets. These findings demonstrated that CDLP and CDNP diets, combined with DTG-based or classical cART regimens, exerted deleterious cardiac effects, promoting myocardial fibrosis that disrupts normal electrical conduction and may predispose to arrhythmogenesis. Tesamorelin prevented these effects, implicating growth hormone pathway dysfunction in the underlying pathology.
Traumatic brain injury (TBI) is a major global health concern. The lateral fluid percussion injury (LFPI) model, widely used in rodents to simulate nonpenetrating TBI, has limited translational applicability due to anatomical differences between rodent and human brains. The common marmoset (Callithrix jacchus), a New World primate with a quasi-gyrencephalic brain, offers a promising alternative. This study aimed to standardize the LFPI model in marmosets by comparing trauma responses across parietal and temporal lobes. Ten adult marmosets underwent LFPI in these regions. Lesion volume was measured using Nissl staining; astrocytic and microglial responses were assessed via GFAP and Iba-1 immunofluorescence, and degenerating neurons were identified with Fluoro-Jade B. Righting reflex time and hemorrhage presence were evaluated as injury markers. Percussion aiming at the temporal lobe injury resulted in the most prominent lesions, epidural and subdural hematomas, and significant neuronal degeneration. Astrocytes showed longer processes after temporal trauma in the cortex and fewer branches in the hippocampal region CA1 than in the naive group. In contrast, hippocampal microglia showed fewer elongated branches in CA1 and dentate gyrus (DG), indicative of a reactive phenotype. Our results highlighted region-specific vulnerability, with temporal injury triggering the most pronounced inflammatory and degenerative responses. The marmoset LFPI model effectively mirrored key aspects of human TBI, supporting its translational relevance.
Citation analysis has emerged as a key area in scientometrics. However, the global movement toward open science, alongside the pervasive “publish or perish” culture, underscores the need to reevaluate the paradigm of citations as a measure of impact and quality. Brazil, a top 15 producer of scientific articles, has established the Lattes Platform, a comprehensive resource data on virtually active researchers in the country. Herein, the Brazilian scientific landscape was analyzed by integrating a widely used global ranking based on large-scale citation metrics with individual-level data from the Lattes Platform. The analysis assessed the impact, distribution, and disparities of Brazilian science across disciplines, geographic regions, and institutional affiliations from 2019-2023. Results showed that Brazilian researchers account for approximately 0.43% of the world's most cited scientists, a significant underrepresentation relative to Brazil's population share and scientific potential. Most highly cited scientists are concentrated in three states within the Southeast region, reflecting longstanding economic and infrastructural advantages. The majority of top Brazilian scientists work in Life Sciences, with particular representation in the subfields Zoology, Tropical Medicine, and Mycology & Parasitology. While Brazil's scientific output compares favorably with other South American and African countries, it remains behind nations with higher gross domestic products per capita and Human Development Index. Nonetheless, 73% of the most cited researchers receive national Research Productivity Grants, indicating a positive correlation between citation and qualified scientific excellence. These findings offer a deeper understanding of Brazilian scientific production from a citation perspective and advocate for strategic policy shifts.
Bladder cancer (BCa) is a histologically and molecularly heterogeneous disease and is one of the leading causes of cancer death globally. The main risk factors are sex (with incidence 3 to 4 times higher in men), tobacco usage, occupational exposure to carcinogens, and persistent infections, such as those caused by Schistosoma haematobium. Urine and the bladder were recently confirmed to be non-sterile, prompting investigations into the urinary and intratumoral microbiomes and their roles in tumor stage, prognosis, and therapy response. In this context, the role of the urinary and intratumoral microbiome in bladder carcinoma is among the most promising areas in translational uro-oncology. Recent evidence demonstrates the presence and diversity of microbial communities in both urine and bladder cancer tissue, with patterns associated with tumor stage and prognosis. Chronic inflammation, genotoxin production, altered carcinogen metabolism, and modulation of the immune microenvironment are biological processes that provide a rationale for the functional role of these microorganisms in the bladder. Furthermore, microbial profiles have been correlated with responses to intravesical therapies (such as BCG - Bacillus Calmette-Guérin) and, potentially, with systemic immunotherapies. The microbiome can help identify predictors of treatment response and potential adjuvant interventions, and offers a non-invasive, translational pathway for diagnosis and surveillance. This review summarizes current evidence on the microbiome in bladder cancer patients and its prognostic and therapeutic potential.
