There are significant gaps in understanding the extent of the damage caused by COVID-19, with few publications examining its link to contrast sensitivity function (CSF). The aim of the present study was to evaluate CSF at low, medium, and high spatial frequencies in individuals with and without a history of COVID-19. Thirty adults, both male and female, aged between 18 and 49 years, participated in the study, 15 with a history of COVID-19 and 15 without. CSF was measured using Metropsis software (version 11) and vertical sine-wave gratings with spatial frequencies ranging from 0.2 to 19.8 cycles per degree (cpd). The results indicated COVID-19-related changes in CSF at spatial frequencies of 6.1 (U=36.00; P=0.003; r=-0.55), 13.2 (U=29.00; P=0.001; r=-0.61), 15.9 (U=17.00; P=0.001; r=-0.70), and 19.8 cpd (U=13.00; P=0.001; r=-0.73). The observed decrease in CSF within specific spatial frequency bands suggested that the visual system of individuals exposed to COVID-19 required higher contrast levels to detect high spatial frequencies. This psychophysical finding indicated that COVID-19 altered the functioning of the visual system and likely affected the neural mechanisms responsible for processing high spatial frequencies.

Endometrial cancer (EC) is the most common pelvic gynecologic malignancy in developed countries, and its incidence is also increasing in developing countries. Endometrioid endometrial carcinoma (EEC) is the most frequent subtype. EEC is often associated with favorable clinicopathological features and a good prognosis, especially when diagnosed in stage I. Although some patients have no signs to predict locally advanced or metastatic disease, they may present tumor relapse in the future. There is no biomarker capable of predicting the relapse of stage I EEC. The present study applied a transcriptome analysis to identify differentially expressed genes in stage I EEC, comparing relapsed with non-relapsed tumors. The estrogen receptor 1 gene (ESR1) was overexpressed in EEC stage I samples from patients who developed relapse by 4.3-fold compared to non-relapsed tumors. Subsequently, an independent set of 64 stage I EEC samples was used to validate ESR1 gene overexpression in relapsed tumors and assess estrogen receptor alpha (ERα) protein levels. ESR1 was confirmed to be overexpressed in samples from relapsed tumors, and its expression level was an independent prognostic variable for disease-free (hazard ratio=7.25) and overall survival (hazard ratio=5.15). In contrast, Erα did not show different values between relapsed and non-relapsed tumors. We concluded that ESR1 overexpression is a biomarker for poor prognosis in stage I EEC.

The primary objective of the present study was to identify differentially expressed genes (DEGs) associated with castration-resistant prostate cancer (CRPC) to verify the potential mechanism of CRPC progression. DEGs from CRPC datasets were filtered with a P<0.05 and Spearman correlation coefficient ≥0.3. Serpin peptidase inhibitor, clade A member 3 (SERPINA3), was uniquely present in three CRPC datasets, and its low expression in CRPC was confirmed in cell lines and tissues. Colony formation, transwell assays, and subcutaneous tumor formation experiments in mice demonstrated that overexpression of SERPINA3 may significantly inhibit the proliferation and invasion of PC3 cells. Mechanistic studies revealed that, in prostate cancer (PCa), SERPINA3 can activate the interleukin (IL)-17 and tumor necrosis factor (TNF)α signaling pathways by promoting the expression of CXC chemokine ligand 2 (CXCL2), thereby increasing the recruitment of M1 macrophages into the tumor microenvironment and inhibiting the progression of PCa. The current results indicated that the expression of SERPINA3 may be negatively correlated with CRPC, and it could promote the M1 polarization of macrophages and inhibit the progression of CRPC by increasing the expression of CXCL2.

Bladder cancer is the most prevalent malignancy of the urinary tract, with significant advancements in treatment achieved over recent decades. Nonetheless, the immunological mechanisms underlying bladder cancer progression remain elusive, and only a limited number of patients derive benefit from current immune checkpoint inhibitors. Here, we conducted a single-cell RNA sequencing analysis of 44,022 cells from peripheral blood mononuclear cell samples of bladder cancer patients and a healthy donor. Our findings indicated that the proportions of T cells and neutrophils are higher in bladder cancer patients than in the healthy donor. LAG3, HAVCR2, and CTLA4 had elevated expression levels in CD8-T2-GZMK cell clusters from patients. CD8-T7-STMN1 cells highly expressed ITGAE, CD38, and STMN1. Furthermore, NK3-CMC1, more prevalent in patients, showed a high expression of TIGIT. Additionally, Bcell2-TCL1A and Bcell3-MS4A1 were characterized by the high expression of inhibitory receptor marker genes. Gene set variation analysis suggested that Mono4-THBS1 may play a role in promoting tumor hypoxia and angiogenesis. Neu-FCGR3B exhibited high levels of IL4R and CD274 expression. Our study indicated that LAG-3 and TIM-3 may serve as novel potential immune checkpoint inhibitors in bladder cancer treatment. The phenotypes of NK3-CMC1, Bcell2-TCL1A, and Bcell3-MS4A1 might be altered by tumor progression. Mono4-THBS1 could potentially be a source of tumor-enriched monocyte-like cells. Neu-FCGR3B may play a detrimental role in the anti-tumor response and could emerge as a predictive marker for bladder cancer. Overall, these high-resolution transcriptomic data offer invaluable insights for identifying new therapeutic targets and biomarkers in bladder cancer immunotherapy.

The aim of this study was to explore sex differences in neuromuscular fatigue during a severe-intensity cycling exercise. Twenty-four healthy participants (12 women and 12 men) cycled at 80% of the difference between gas exchange threshold and maximal power output to the limit of tolerance. Neuromuscular fatigue was assessed by the decrease in maximal voluntary contraction of the knee extensors before and after exercise, and central and peripheral fatigue was measured by the decrease in voluntary activation and quadriceps potentiated twitch force before and after exercise. Women presented shorter time to task failure (P=0.025) and lower levels of neuromuscular fatigue (P=0.006) and peripheral fatigue (P<0.001) than men. Women and men showed different patterns of muscle activation during exercise, with women presenting greater muscle activation at the beginning of exercise and sustaining this elevated muscle activation throughout exercise, while men increased muscle activation from the beginning to the end of exercise. In conclusion, women had lower levels of neuromuscular fatigue, mainly caused by lower levels of peripheral fatigue, and a different muscle activation pattern in an exhaustive severe-intensity cycling exercise.

Biomaterials stimulate diverse biological responses, including inflammation, wound healing, foreign body reactions, and fibrous encapsulation, all critical for evaluating biocompatibility and effectiveness. These responses are influenced by the material's physicochemical and biological properties, such as composition, texture, and surface characteristics. Adverse reactions, such as severe inflammation or fibrous encapsulation, can hinder tissue integration, jeopardizing patient health and increasing healthcare costs. This review aimed to summarize the current scientific evidence on biological responses to biomaterials. A systematic search was conducted through multiple databases (VHL, PubMed, SCOPUS, EMBASE, and Web of Science) including in vitro and in vivo studies that compared biomaterial interactions with the natural immune response (innate and adaptive). From the 791 articles identified, 25 met strict inclusion criteria. These studies revealed variations in immune responses and material surface characteristics, highlighting advancements made to enhance tissue integration. Bioactive materials demonstrated greater potential for tissue regeneration, while inert materials triggered moderate inflammatory reactions. This variability emphasizes the need for a personalized biomaterial selection, considering both short-term biocompatibility and long-term tissue functionality. This review underscores the importance of comprehensive evaluation to optimize biomaterial performance in clinical applications.

Antiretroviral therapy (ART) is essential to reduce viral load and restore CD4+ T cell levels in people living with HIV/AIDS (PLWHA). However, different treatment protocols influence the levels of cytokines, important mediators of the immune response. This study aimed to evaluate cytokine levels in PLWHA on therapy with tenofovir (TDF), lamivudine (3TC), and dolutegravir (DTG). The results showed that PLWHA on treatment had a significant increase in CD4+ T lymphocyte levels and a reduction in CD8+ T lymphocyte levels compared to naive (untreated) individuals. Furthermore, PLWHA treated with TDF/3TC/DTG had a significant reduction in interleukin (IL)-4 and IL-10 levels (P<0.02; P=0.047) compared to other ART regimens. Naive individuals had higher levels of IL-2 and interferon (IFN)-γ, while their levels of tumor necrosis factor (TNF), IL-4, and IL-10 were lower. These findings suggested that TDF/3TC/DTG treatment modulated cytokines, reducing chronic inflammation and improving the immune response in PLWHA. The decrease in anti-inflammatory cytokines, such as IL-4 and IL-10, may be associated with better regulation of the immune system, resulting in greater control of infection and a balanced inflammatory response.

Cancer is the second leading cause of death worldwide. Cancer cachexia is a multifactorial catabolic syndrome responsible for almost one third of cancer-related deaths. Drug repurposing has been used in oncological research and drugs like clenbuterol and metformin seem to be reasonable candidates in the context of cancer cachexia, because the former is a β2-agonist that stimulates muscle gain and the latter has anti-inflammatory properties. The aim of this study was to assess the effects of a short-term treatment with metformin and clenbuterol, isolated or combined, on tumor growth and cancer cachexia parameters in Walker 256 tumor-bearing rats, a model of cancer cachexia. To this end, Wistar rats were separated into 8 groups and 4 of them were injected with Walker 256 tumor cells (W groups). Control (C) and W groups received the following treatments: metformin (M), clenbuterol (Cb), or metformin combined with clenbuterol (MCb). Body and tumor weight, metabolic parameters, and oxidative damage in the tumor were assessed. Compared to the C group, the W group showed body weight loss, hypoglycemia, hyperlactatemia, and hypertriacylglycerolemia. None of the treatments could reverse body weight loss, although they reversed the alterations of the assessed plasma metabolic parameters. Surprisingly, only clenbuterol alone reduced tumor weight. Hydrogen peroxide production and lipid peroxidation in tumor tissue was increased in this group. In conclusion, metformin and clenbuterol ameliorated metabolic cachexia parameters in Walker tumor-bearing rats, but only clenbuterol reduced the tumor weight, probably, through a lipid peroxidation-dependent cell death.

Sirtuins (SIRTs) are key regulators of cellular metabolism, involved in a wide range of physiological and pathological processes. However, there is scarce knowledge about the effect of sugar consumption and physical activity on SIRTs in kidney disorders. Here, we evaluated the impact of prolonged consumption of an isocaloric high-sugar diet (HSD) and physical training on the modulation of renal Sirts and the link between these alterations and possible obesity-associated kidney damage. Newly weaned male Wistar rats were fed a standard chow diet (STD) or HSD ad libitum and then subjected or not to regular workload swimming training for 18 weeks. Morphometric and biochemical parameters were analyzed, and the kidneys were removed for lipid quantification, histological analysis, and for Sirts1-7 expression. HSD led to the development of obesity, increased serum triglyceride levels, and glucose intolerance, regardless of higher caloric consumption. However, training was able to partially inhibit the HSD-induced obesogenic effect. No changes were identified in kidney mass, lipid content, histology, and creatinine clearance among the groups; these results were associated with a decrease in the renal expression of Sirt2-3 and Sirt7; however, training was able to reverse this modulation. The interaction between HSD and training led to an increase in Sirt4-7. However, Sirt1 remained constant among experimental groups. In conclusion, our results indicated that the transcriptional modulation of Sirts precedes HSD-induced damage and loss of kidney function, as well as a possible protective adaptive response of physical exercise on long-term Sirts expression.

Osteosarcoma (OS) remains the most common bone tumor and the prognosis for many patients remains stagnant due to the unsatisfactory therapeutic effect of conventional treatment regimens. This research explored the effect and mechanism of a novel natural product, Eriocalyxin B (EB), in pathogenesis and immunotherapy in OS. Cell Count Kit 8 assay, colony formation assay, and wound healing assay were employed to detect the proliferative, colony-forming, and migratory abilities of human OS cells following EB treatment. Moreover, xenograft growth assay was performed to assess the effect of EB on OS in vivo. Subcutaneous OS models constructed in immunocompetent mice were employed to evaluate the effect of EB treatment in combination with immune checkpoint blockades (ICBs) PD1ab and CTLA4ab. Immunohistochemistry (IHC) staining was utilized to detect the level of CD8+ T cells infiltration and Ki67 expression. TARGET database, RNA interference technology, and qPCR assay were employed to explore the mechanism of EB on OS. EB inhibited the proliferative, colony-forming, and migratory abilities of the human OS cells MG63 and U2OS both in vitro and in vivo. TARGET data analysis demonstrated that up-regulation of TCEA3 was significantly negatively correlated with overall survival in OS patients. EB exerted anti-tumor activity via downregulation of TCEA3. EB, in conjunction with ICBs, synergistically optimized anti-tumorigenic activity against OS in immunocompetent mice. EB may promote infiltration of CD8+ T cells and down-regulate Ki67 expression. These results signaled that EB may have a role as a candidate therapeutic or preventive agent for the treatment of OS.

Necrotizing enterocolitis (NEC) is a severe intestinal disease of multifactorial origin that primarily affects premature infants. Approximately 27% of NEC babies develop short gut (SG) secondary to extensive intestinal resection, and 10% will have chronic dependence on total parenteral nutrition. We evaluated the Botox treatment in SG model rats. Twenty-day-old weanling male rats (weight range 38-70 g, n=72) were divided into four groups (n=18 each): 1) Control (fed a regular liquid diet); 2) Botox (Control submitted to laparotomy and intestinal injection of Botox®); 3) SG (short gut); and 4) SG and Botox (SG+Botox®). After seven post-operative days, samples were collected for biometrics [body weight (BW), intestine weight (IW) and IW/BW ratio (IBR), and intestine length (IL) and height (IH)], histometric analysis [villous height (VH), crypt depth (CD), muscular thickness (MT), and PCNA index)], and intestinal transit time (ITT). BW, IW, and IL decreased in SG (P<0.05). IH, VH, and PCNA index increased in Botox groups [Control = SG < Botox and SG+Botox (P<0.05)], CD increased in Botox, SG, and SG+Botox (P<0.005), and MT was higher in SG and SG+Botox. Botox groups had lower ITT (P<0.05). Botox provided dilatation and histological changes in SG. These findings suggested that Botox improved adaptation and might be applied in SG with promising results.

Although correlated to peak oxygen uptake (VO2), the six-minute walk test (6MWT) alone cannot provide precise physiological insight regarding the specific cause(s) of exercise limitations. We aimed to analyze whether 6MWT is able to properly detect differences in the cardiorespiratory responses between patients with stable coronary artery disease (SCAD) and those with ischemic cardiomyopathy (IC) and determine whether the degree of abnormality in ejection fraction is related with impaired submaximal exercise capacity. Twenty-two subjects with SCAD and 19 subjects with IC underwent a 6MWT while simultaneously using a mobile telemetric cardiopulmonary monitor to assess cardiorespiratory responses. VO2 response at exercise onset was used to obtain VO2 on-kinetics, and the slope of ventilation vs carbon dioxide output (VE/VCO2) was calculated. IC subjects exhibited significantly delayed VO2 on-kinetics compared with the SCAD group (P<0.01) and higher VE/VCO2 slope (IC=40.45 [95%CI: 39.76 to 41.1] vs SCAD=34.36 [95%CI: 34.03 to 34.69], P=0.001). The left ventricular ejection fraction (LVEF) was moderately correlated with VO2 on-kinetics in the SCAD group, but no relationship was found in the IC group. Pulmonary function was correlated with the VE/VCO2 slope only in the IC group. Subjects with IC presented slower VO2 on-kinetics during the 6MWT than those with SCAD. Once reduction in left ventricular function is achieved, LVEF had no association with exercise capacity. Pulmonary function could help identify IC patients at risk of ventilatory inefficiency and may add diagnostic power to the 6MWT.

Head and neck squamous cell carcinoma (HNSCC) is a common malignant tumor that poses a major hazard to people's health. ZC3H12D, which belongs to the family of CCCH-type zinc finger-containing proteins, is a negative regulator with a key function in immune modulation. However, it is still unclear how ZC3H12D affects the immune infiltration and prognosis of HNSCC. In this study, the data obtained from various databases were used to assess ZC3H12D expression in HNSCC and in various tumors under the HNSCC classification. The association between clinical features and ZC3H12D expression in HNSCC was evaluated using the UALCAN database. Additionally, a ROC curve was employed to analyze the diagnostic value of ZC3H12D. The effect of ZC3H12D on prognosis was assessed using Kaplan-Meier curves, Cox analysis, and the nomogram model. Gene Set Enrichment Analysis, Gene Ontology, and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were employed to investigate the underlying role of ZC3H12D in HNSCC. The association between ZC3H12D expression and the tumor microenvironment and immune checkpoints were investigated by TIMER2 and Tumor Immune Single Cell Hub 2 databases and various packages in R. The findings demonstrated a significant up-regulation of ZC3H12D expression in HNSCC, while ZC3H12D expression was found to be associated with clinical parameters. Our study also demonstrated that ZC3H12D could act as a potential prognostic biomarker for HNSCC, especially oral squamous cell carcinoma. Additional analyses have shown that ZC3H12D was associated with common immune checkpoint genes and may be related to immune infiltration in HNSCC.

Alpinia zerumbet, a plant native to East Asia, is widely found on the Brazilian coast, where it is used in folk medicine as an antihypertensive, diuretic, and anxiolytic. This study investigated the effects of the hydroalcoholic extract obtained from Alpinia zerumbet leaves (AZE) on cardiovascular changes and oxidative status in spontaneously hypertensive rats (SHR). SHR and Wistar-Kyoto male rats, 90 days old, treated or not with AZE (50 mg/kg/day in drinking water) for six weeks, were used in this study. Blood pressure (BP) was assessed weekly by tail plethysmography. At the end of treatment, the animals were anesthetized with thiopental (70 mg/kg, ip), blood was collected through abdominal aorta puncture, the thoracic aorta and left ventricle were isolated for morphometric analysis and immunostaining of NOX-4, SOD-2, 8-isoprostane, and angiotensin II AT1 receptors (AT1R), and the mesenteric arterial bed (MAB) was isolated for the assessment of vascular function. Oxidative damage in lipids and proteins and the enzymatic antioxidant activity were evaluated in plasma samples by spectrophotometry. AZE normalized BP in SHR. Although the treatment did not improve the MAB vascular dysfunction, it reversed the cardiovascular remodeling in the aorta and left ventricle. In addition, AZE improved antioxidant activity in plasma and SOD-2 immunostaining in the thoracic aorta and left ventricle, decreased protein carbonylation in plasma, and reduced 8-isoprostane, NOX-4, and AT1R immunostaining in the cardiovascular system. The results suggested that AZE reversed hypertension and cardiovascular remodeling in SHR, which was associated with lower oxidative stress and AT1R.

Frailty is a significant risk factor for adverse outcomes in elderly surgical patients. Gait speed assessment is a new tool recently used to stratify risk for these pre-operative adverse outcomes. In this prospective study of 392 frail elderly patients undergoing abdominal surgery, we investigated the predictive value of preoperative gait speed for postoperative outcomes. Patients were divided into two groups based on their 6-meter gait speed: normal (≥0.8 m/s, n=184) and slow (<0.8 m/s, n=208). The slow group was older, had more comorbidities, and higher American Society of Anesthesiologists (ASA) grades (P<0.05). They also had significantly higher rates of 30-day overall complications (38.9 vs 18.5%, P<0.01), severe complications (12.0 vs 4.3%, P<0.01), and 1-year mortality (15.4 vs 6.5%, P=0.008) compared to the normal group. Pulmonary infection, wound infection, and delirium were the most common complications. Multivariate logistic regression confirmed slow gait speed as an independent risk factor for 30-day complications (OR=2.38, 95%CI: 1.41-4.01) and 1-year mortality (OR=2.19, 95%CI: 1.07-4.48). Our findings demonstrated that preoperative 6-meter gait speed effectively predicted short-term complications and mid-term mortality in frail elderly patients undergoing abdominal surgery. This suggests the need for individualized perioperative management strategies for high-risk patients with slow gait speed to potentially improve their prognosis.