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During the COVID-19 pandemic, many patients in intensive care units (ICUs) were affected by invasive fungal infections, including aspergillosis, contributing to a high mortality rate. Diagnosing proven COVID-19-associated pulmonary aspergillosis (CAPA) requires clinical and radiological evaluations, along with laboratory testing of bronchoalveolar lavage samples or lung biopsies. However, these procedures and equipment are often inaccessible in developing countries or regions with limited resources, including Brazil. Consequently, alternative diagnostic methods, such as measuring Aspergillus galactomannan (GM) in tracheal aspirate (TA), have been explored for CAPA diagnosis. Nonetheless, research on the efficacy of TA-based diagnostic tests is limited. This study aimed to assess the performance of the IMMY® Sona Aspergillus lateral flow assay (LFA) for GM detection in TA samples from 60 ICU patients with suspected CAPA at two tertiary hospitals in Campo Grande, Brazil. The ELISA method (Platelia Aspergillus AG, Bio-Rad®) was used to detect Aspergillus GM in TA samples, serving as the microbiological criterion and reference test. Fifteen patients (12.4%) were identified as having possible CAPA. The overall accuracy of LFA was 94%, and the tests demonstrated an agreement of 93.1% (Cohen's kappa of 0.83). Based on our findings, the LFA for Aspergillus GM detection in TA samples exhibited excellent performance, proving to be a valuable diagnostic tool for potential CAPA. In a systematic review, two studies were included, and the meta-analysis revealed pooled estimates provided a sensitivity of 86% (95% CI, 80%-91%) and specificity of 93% (95% CI, 86%-97%). The diagnostic odds ratio (DOR) for identification of Aspergillus using LFA was 103.38 (95% CI, 38.03-281.03). Despite its lower sensitivity compared to our study, the LFA appears to be a promising diagnostic option for CAPA, particularly in suspected cases that have not received antifungal therapy. This enables timely antifungal treatment and could reduce mortality rates in regions where bronchoscopy is unavailable or limited.

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INTRODUCTION: Bipolar disorder (BD) is a chronic pathology that is associated with several impairments throughout a patient's life, including decreased sexual function. Despite the importance in quality of life (QoL), functionality and medication adherence, it is still little investigated in these patients. OBJECTIVE: To compare the sexual function of patients with Bipolar Disorder type I (BD-I), in remission, with healthy controls (HC) and to investigate the clinical and socio-demographic characteristics associated with sexual function in these individuals. Also, to assess the QoL in patients with and without sexual dysfunction (SD). METHODS: Cross-sectional study with 132 patients with BD-I in euthymic phase and 61 HCs from an outpatient clinic. All the participants were evaluated through the Arizona Sexual Scale (ASEX) and the brief version of the World Health Organization Quality of Life Assessment (WHOQoL-BREF). The patients with BD-I were compared with the HCs. The patients were divided into two groups: the ones diagnosed with SD and the ones without it. RESULTS: The patients with BD-I had higher rates of SD (42.4%) compared to the HCs (16.4%) (OR 3.67, 95% CI 1.55 - 8.67; p=0.003). SD in patients was associated with being women (p=0.001), older age (p=0.003) and having a longer duration of untreated illness (p=0.010). Patients with SD had worse QoL scores compared to those without SD. CONCLUSION: Patients with BD-I have a high prevalence of SD and this was associated with worse QoL scores in all domains.

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Cisplatin (CP) is a chemotherapy drug widely prescribed to treat various neoplasms. Although fundamental for the therapeutic action of the drug, its cytotoxic mechanisms trigger adverse effects in several tissues, such as the kidney, liver, and heart, which limit its clinical use. In this sense, studies point to an essential role of damage to nuclear and mitochondrial DNA associated with oxidative stress, inflammation, and apoptosis in the pathophysiology of tissue injuries. Due to the limitation of effective preventive and therapeutic measures against CP-induced toxicity, new strategies with potential cytoprotective effects have been studied. Therefore, this article is timely in reviewing the characteristics and main molecular mechanisms common to renal, hepatic, and cardiac toxicity previously described, in addition to addressing the main validated strategies for the current management of these adverse events in clinical practice. We also handle the main promising antioxidant substances recently presented in the literature to encourage the development of new research that consolidates their potential preventive and therapeutic effects against CP-induced cytotoxicity.

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Regular exercise training can lead to several health benefits, reduce mortality risk, and increase life expectancy. On the other hand, a sedentary lifestyle is a known risk factor for chronic diseases and increased mortality. Acute kidney injury (AKI) and chronic kidney disease (CKD) represent a significant global health problem, affecting millions of people worldwide. The progression from AKI to CKD is well-recognized in the literature, and exercise training has emerged as a potential renoprotective strategy. Thus, this article aims to review the main molecular mechanisms underlying the renoprotective actions of exercise training in the context of AKI and CKD, focusing on its antioxidative, anti-inflammatory, anti-apoptotic, anti-fibrotic, and autophagy regulatory effects. For that, bibliographical research was carried out in Medline/PubMed and Scielo databases. Although the pathophysiological mechanisms involved in renal diseases are not fully understood, experimental studies demonstrate that oxidative stress, inflammation, apoptosis, and dysregulation of fibrotic and autophagic processes play central roles in the development of tissue damage. Increasing evidence has suggested that exercise can beneficially modulate these mechanisms, potentially becoming a safe and effective non-pharmacological strategy for kidney health protection and promotion. Thus, the evidence base discussed in this review suggests that an adequate training program emerges as a valuable tool for preserving renal function in experimental animals, mainly through the production of antioxidant enzymes, nitric oxide (NO), irisin, IL-10, and IL-11. Future research can continue to explore these mechanisms to develop specific guidelines for the prescription of exercise training in different populations of patients with kidney diseases.

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Maternal probiotic supplementation has been found to have a positive impact on the gut health of piglets, not only during the lactation period, but also after weaning. Providing probiotics to nursery pigs is also a common strategy for supplementation. The goal of this study was to evaluate which would be the most effective strategy to improve nutrient digestibility, energy metabolism, and intestinal health in weaned pigs considering the maternal or nursery options. A total of 32 newly weaned pigs were randomly split into a 2 × 2 factorial arrangement considering maternal probiotic supplementation (with or without) in gestation-lactation and probiotic supplementation in the nursery period (with or without). After weaning, experimental diets were provided for 22 days. Total fecal and urine collection was performed from day 15 to 21. Blood samples were collected from all pigs on days 3 and 22 of the experiment to assess serum biochemistry and intestinal permeability. All pigs were euthanized on day 22 for intestinal tissue collection. Pigs born from probiotic-fed sows had greater (p < 0.05) total tract digestibility of dry matter (+1%) and gross energy (+1.3%), and greater (p < 0.05) metabolizable energy coefficient (+1.3%), which resulted in a 46 kcal/kg increase (p < 0.05) in the metabolizable energy content of the diet. Nitrogen intake (p = 0.035), uptake (p = 0.007), and retention (p = 0.012) were all increased in these pigs. Fecal moisture was reduced in pigs born from probiotic-fed sows and pigs fed the probiotic diet only in the nursery (p < 0.05). Pigs born from probiotic-fed sows had reduced intestinal permeability by 16% (p < 0.05), whereas pigs fed the probiotic diet in the nursery only tended to improve this response (p < 0.10). The villus:crypt ratio of pigs born from probiotic-fed sows was greater compared to the control (p < 0.05), while serum levels of alanine aminotransferase were lower (p < 0.05). Pigs born from probiotic-fed sows had increased nutrient digestibility and improved gut health. Therefore, it is concluded that supplementing the sow diets with probiotics rather than just providing diets in the nursery phase is an advantageous strategy.

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BACKGROUND: Trypanosoma cruzi and HIV coinfection can evolve with depression of cellular immunity and increased parasitemia. We applied quantitative PCR (qPCR) as a marker for preemptive antiparasitic treatment to avoid fatal Chagas disease reactivation and analyzed the outcome of treated cases. METHODOLOGY: This mixed cross-sectional and longitudinal study included 171 Chagas disease patients, 60 coinfected with HIV. Of these 60 patients, ten showed Chagas disease reactivation, confirmed by parasites identified in the blood, cerebrospinal fluid, or tissues, 12 exhibited high parasitemia without reactivation, and 38 had low parasitemia and no reactivation. RESULTS: We showed, for the first time, the success of the timely introduction of benznidazole in the non-reactivated group with high levels of parasitemia detected by qPCR and the absence of parasites in reactivated cases with at least 58 days of benznidazole. All HIV+ patients with or without reactivation had a 4.0-5.1 higher chance of having parasitemia than HIV seronegative cases. A positive correlation was found between parasites and viral loads. Remarkably, treated T. cruzi/HIV-coinfected patients had 77.3% conversion from positive to negative parasitemia compared to 19.1% of untreated patients. Additionally, untreated patients showed ~13.6 times higher Odds Ratio of having positive parasitemia in the follow-up period compared with treated patients. Treated and untreated patients showed no differences regarding the evolution of Chagas disease. The main factors associated with all-cause mortality were higher parasitemia, lower CD4 counts/µL, higher viral load, and absence of antiretroviral therapy. CONCLUSION: We recommend qPCR prospective monitoring of T. cruzi parasitemia in HIV+ coinfected patients and point out the value of pre-emptive therapy for those with high parasitemia. In parallel, early antiretroviral therapy introduction is advisable, aiming at viral load control, immune response restoration, and increasing survival. We also suggest an early antiparasitic treatment for all coinfected patients, followed by effectiveness analysis alongside antiretroviral therapy.

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OBJECTIVE: The present study aimed to assess the relationship between keratinized mucosa width and peri-implant diseases, namely peri-implant mucositis and peri-implantitis. MATERIALS AND METHODS: Ninety-one dental implants in function for ≥ 6 months from 40 partially or completely edentulous non-smoker subjects (24 females and 16 males) were evaluated clinically and radiographically. The width of keratinized mucosa, probing depth, plaque index, bleeding on probing, and marginal bone levels were assessed. Keratinized mucosa width was categorized as ≥ 2 mm or < 2 mm. RESULTS: There was no statistically significant association between keratinized buccal mucosa width and peri-implant mucositis or peri-implantitis (p ≥ 0.37). In the regression analysis, peri-implantitis was associated with longer implant function time (RR: 2.55, 95% CI: 1.25-11.81, p = 0.02) and implants in the maxilla (RR: 3.15, 95% CI: 1.61-14.93, p = 0.003). Mucositis was not associated with any of the factors analyzed. CONCLUSION: In conclusion, in the present sample, keratinized buccal mucosa width was not associated with peri-implant diseases, suggesting that a band of keratinized mucosa may not be necessary to maintain peri-implant health. Prospective studies are required to better understand its role in the maintenance of peri-implant health.

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Cutinases are serine esterases that belong to the α/ß hydrolases superfamily. The natural substrates for these enzymes are cutin and suberin, components of the plant cuticle, the first barrier in the defense system against pathogen invasion. It is well-reported that plant pathogens produce cutinases to facilitate infection. Fusarium verticillioides, one important corn pathogens, is an ascomycete upon which its cutinases are poorly explored. Consequently, the objective of this study was to perform the biochemical characterization of three precursor cutinases (FvCut1, FvCut2, and FvCut3) from F. verticillioides and to obtain structural insights about them. The cutinases were produced in Escherichia coli and purified. FvCut1, FvCut2, and FvCut3 presented optimal temperatures of 20, 40, and 35 °C, and optimal pH of 9, 7, and 8, respectively. Some chemicals stimulated the enzymatic activity. The kinetic parameters revealed that FvCut1 has higher catalytic efficiency (Kcat/Km) in the p-nitrophenyl-butyrate (p-NPB) substrate. Nevertheless, the enzymes were not able to hydrolyze polyethylene terephthalate (PET). Furthermore, the three-dimensional models of these enzymes showed structural differences among them, mainly FvCut1, which presented a narrower opening cleft to access the catalytic site. Therefore, our study contributes to exploring the diversity of fungal cutinases and their potential biotechnological applications.

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ABSTRACT Objective: To evaluate the possible renal and hepatic alteration by root canal filling pastes in mice. Material and Methods: Fifty-four mice were divided into nine groups and received one polyethylene tube implant containing two filling pastes (CTZ or calcium hydroxide pastes). Empty polyethylene tubes were used as a negative control. All tubes were implanted subcutaneously in the back of the mice. After time intervals of 7, 21, and 63 days, 1.5 mL of blood was collected by cardiac puncture, and serum samples were used for serological testing. Urea, creatinine, aspartate transferase (AST), alanine transferase (ALT), alkaline phosphatase (ALP), and gamma-glutamyltransferase (GGT) were evaluated. Data were analyzed by 2-way ANOVA (p<0.05). Results: When comparing CTZ and calcium hydroxide pastes and empty tubes and experimental time intervals, no significant differences in the results were found for any of the biochemical parameters analyzed (p>0.05). No differences were observed in the interactions (material*experimental time intervals) and the biochemical parameters analyzed (p>0.05). Conclusion: CTZ and calcium hydroxide pastes did not cause hepatic and renal alterations in mice, demonstrating the pastes' safety.

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Circulating senescent CD8+ T (T8sen) cells are characterized by a lack of proliferative capacities but retain cytotoxic activity and have been associated to resistance to immunotherapy in patients with advanced non-small cell lung cancer (aNSCLC). We aimed to better characterize T8sen and to determine which factors were associated with their accumulation in patients with aNSCLC. Circulating T8sen cells were characterized by a higher expression of SA-ßgal and the transcription factor T-bet, confirming their senescent status. Using whole virome profiling, cytomegalovirus (CMV) was the only virus associated with T8sen. CMV was necessary but not sufficient to explain high accumulation of T8sen (T8senhigh status). In CMV+ patients, the proportion of T8sen cells increased with cancer progression. Last, CMV-induced T8senhigh phenotype but not CMV seropositivity itself was associated with worse progression-free and overall survival in patients treated with anti-PD-(L)1 therapy but not with chemotherapy. Overall, CMV is the unique viral driver of T8sen-driven resistance to anti-PD-(L)1 antibodies in patients with aNSCLC.

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(1) Background: Mammary neoplasms in female dogs share many similarities with the same tumor class in humans, rendering these animals a valuable preclinical model for studying novel therapies against breast cancer. The intricate role of extracellular vesicles (EVs), particularly exosomes, in breast carcinogenesis, by transferring specific proteins to recipient cells within the tumor microenvironment, underscores their significance. Melatonin, a hormone recognized for its antitumor effects, adds another layer of intrigue. (2) Methods: EVs obtained from the plasma of dogs diagnosed with mammary tumors were co cultivated with the benign epithelial lineage E-20 using DMEM. The experiment comprised four 24 h treatment groups: control, EVs, melatonin, and EVs + melatonin. A series of assays were conducted, including colony formation, proliferation, and cellular migration assessments. Furthermore, we conducted colony formation, proliferation, and cellular migration assays. We performed immunohistochemistry for proteins of the mTOR pathway, including mTOR and AKT. (3) Results: Exosomes alone significantly increased proliferation, migration, and colony formation rates and, upregulated the expression of mTOR and AKT proteins. However, when melatonin was added, a protective effect was observed. (4) Conclusions: These findings contributed to the use of melatonin to modulate EV-mediated signaling in the clinical veterinary oncology of mammary tumors.

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Background: In patients at high risk of thromboembolism who were discharged after hospitalisation due to COVID-19, thromboprophylaxis with rivaroxaban 10 mg/day for 35 days significantly improved clinical outcomes, reducing thrombotic events compared with no post-discharge anticoagulation. The present study aimed to estimate the cost-effectiveness of this anticoagulation strategy. Methods: Using the database of the MICHELLE trial, we developed a decision tree to estimate the cost-effectiveness of thromboprophylaxis with rivaroxaban 10 mg/day for 35 days versus no thromboprophylaxis in high-risk post-discharge patients for COVID-19 through an incremental cost-effectiveness analysis. Findings: 318 patients in 14 centres in Brazil were enrolled in the primary MICHELLE trial. The mean age was 57.1 years (SD 15.2), 127 (40%) were women, 191 (60%) were men, and the mean body-mass index was 29.7 kg/m2 (SD 5.6). Rivaroxaban 10 mg per day orally for 35 days after discharge decreased the risk of events defined by the primary efficacy outcome by 67% (relative risk 0.33, 95% CI 0.12-0.90; p = 0.03). The mean cost for thromboprophylaxis with rivaroxaban was $53.37/patient, and no prophylaxis was $34.22/patient, with an incremental cost difference of $19.15. The effectiveness means obtained in the intervention group was 0.1457, while in the control group was 0.1421, determining an incremental QALY difference of 0.0036. The estimated incremental cost-effectiveness ratio (ICER) was $5385.52/QALY. Interpretation: Extended treatment with Rivaroxaban as thromboprophylaxis after hospital discharge for high-risk patients with COVID-19 is a cost-effective treatment option. Funding: Modest funding was provided by Science Valley Research Institute, São Paulo, Brazil.

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The green microalga Chlamydomonas reinhardtii is a model microorganism for several areas of study. Among the different microalgae species, it presents advantageous characteristics, such as genomes completely sequenced and well-established techniques for genetic transformation. Despite that, C. reinhardtii production is still not easily commercially viable, especially due to the low biomass yield. So far there are no reports of scientometric study focusing only on C. reinhardtii biomass production process. Considering the need for culture optimization, a scientometric research was conducted to analyze the papers that investigated the growth regimes effects in C. reinhardtii cultivation. The search resulted in 130 papers indexed on Web of Science and Scopus platforms from 1969 to December 2022. The quantitative analysis indicated that the photoautotrophic regime was the most employed in the papers. However, when comparing the three growth regimes, the mixotrophic one led to the highest production of biomass, lipids, and heterologous protein. The production of bioproducts was considered the main objective of most of the papers and, among them, biomass was the most frequently investigated. The highest biomass production reported among the papers was 40 g L-1 in the heterotrophic growth of a transgenic strain. Other culture conditions were also crucial for C. reinhardtii growth, for instance, temperature and cultivation process.

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BACKGROUND: Cases of coronavirus disease 2019 (COVID-19) requiring hospitalization continue to appear in vulnerable populations, highlighting the importance of novel treatments. The hyperinflammatory response underlies the severity of the disease, and targeting this pathway may be useful. Herein, we tested whether immunomodulation focusing on interleukin (IL)-6, IL-17, and IL-2, could improve the clinical outcomes of patients admitted with COVID-19. METHODS: This multicenter, open-label, prospective, randomized controlled trial was conducted in Brazil. Sixty hospitalized patients with moderate-to-critical COVID-19 received in addition to standard of care (SOC): IL-17 inhibitor (ixekizumab 80 mg SC/week) 1 dose every 4 weeks; low-dose IL-2 (1.5 million IU per day) for 7 days or until discharge; or indirect IL-6 inhibitor (colchicine) orally (0.5 mg) every 8 hours for 3 days, followed by 4 weeks at 0.5 mg 2x/day; or SOC alone. The primary outcome was accessed in the "per protocol" population as the proportion of patients with clinical improvement, defined as a decrease greater or equal to two points on the World Health Organization's (WHO) seven-category ordinal scale by day 28. RESULTS: All treatments were safe, and the efficacy outcomes did not differ significantly from those of SOC. Interestingly, in the colchicine group, all participants had an improvement of greater or equal to two points on the WHO seven-category ordinal scale and no deaths or patient deterioration were observed. CONCLUSIONS: Ixekizumab, colchicine, and IL-2 were demonstrated to be safe but ineffective for COVID-19 treatment. These results must be interpreted cautiously because of the limited sample size.

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OBJECTIVE: This study aimed to evaluate the perceptions of third-year dental students regarding the application of ergonomic principles in the transition between preclinical and clinical training in Restorative Dentistry. METHODS: We conducted a qualitative observational cross-sectional study. The sample consisted of forty-six third-year dental students at São Paulo State University (Unesp), School of Dentistry, Araraquara. Data was collected using an individual interview recorded on a digital voice recorder. A script containing questions related to the process of adaptation of students to clinical care with a view to ergonomic work posture was used. Data analysis was based on the quali-quantitative technique of Discourse of the Collective Subject (DCS), using Qualiquantisoft®. RESULTS: Most students (97.80%) perceived the need for an adaptation period in the transition from the preclinic to the clinic regarding ergonomic posture requirements; a part of them (45.65%) claimed that they still could not adapt, primarily due to the difference between the laboratory and clinic in the workstation (50.00%). Some students suggested longer preclinical training in a clinical environment to facilitate this transition (21.74%). The dental stool (32.60%) and the dental chair (21.74%) were the external factors that contributed most to making this transition difficult. The difficulty of the restorative dentistry procedure (10.87%) also interfered with posture. Additionally, the most challenging ergonomic posture requirements in the transition period were maintaining 30 to 40 cm between the patient's mouth and operator's eyes (45.65%), positioning the patient in the dental chair correctly (15.22%), and working with the elbows close to the body (15.22%). CONCLUSION: Most students perceived the need for an adaptation period in the preclinical transition to the clinic, attributing difficulties to adopt the ergonomic posture requirements, to use the workstation and to perform the procedures on real patients.

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OBJETIVO: Identificar o conhecimento de estudantes sobre os métodos contraceptivos, antes e após a realização de oficinas sobre a temática. MÉTODOS: Pesquisa-ação, realizada com 38 estudantes do ensino médio. Foram realizadas oficinas com discussão da temática (audiogravadas) e aplicação de pré e pós-teste em outubro de 2022. Utilizou-se a análise de conteúdo temática para as narrativas e cálculo da frequência relativa para as questões fechadas do questionário. RESULTADOS: As narrativas se diferenciam entre as escolas. Os estudantes acreditam que o dispositivo intrauterino é abortivo; conhecem pouco sobre dupla proteção; e associam a pílula anticoncepcional aos benefícios à estética. Após as oficinas houve ampliação dos acertos e incorporação de novos conhecimentos mensurados pelo pós-teste nas duas escolas. CONCLUSÃO: É importante realizar oficinas no ambiente escolar a fim de reduzir danos à saúde e o Programa Saúde na Escola pode ser um facilitador para o acesso às temáticas da sexualidade e saúde reprodutiva.

OBJECTIVE: To identify students' knowledge about contraceptive methods, before and after workshops on the topic. METHODS: Action research, carried out with 38 high school students. Workshops were held with discussion of the topic (audiorecorded) and application of pre- and post-tests in October 2022. Thematic content analysis was used for the narratives and calculation of the relative frequency for the closed questions of the questionnaire. RESULTS: The narratives differ between schools. Students believe that the intrauterine device is abortifacient; they know little about double protection; and they associate the contraceptive pill with aesthetic benefits. After the workshops, there was an increase in correct answers and the incorporation of new knowledge measured by the post-test in both schools. CONCLUSION: It is important to hold workshops in the school environment in order to reduce harm to health and the School Health Program can be a facilitator for access to sexuality and reproductive health topics.

OBJETIVO: Identificar los conocimientos de los estudiantes sobre métodos anticonceptivos, antes y después de los talleres sobre el tema. MÉTODOS: Investigación acción, realizada con 38 estudiantes de secundaria. Se realizaron talleres con discusión del tema (audiograbados) y aplicación de pre y post pruebas en octubre de 2022. Para las narrativas se utilizó análisis de contenido temático y cálculo de la frecuencia relativa para las preguntas cerradas del cuestionario. RESULTADOS: Las narrativas difieren entre escuelas. Los estudiantes creen que el dispositivo intrauterino es abortivo; saben poco sobre la doble protección; y asocian la píldora anticonceptiva con beneficios estéticos. Luego de los talleres, hubo un aumento en las respuestas correctas y la incorporación de nuevos conocimientos medidos por el post-test en ambas escuelas. CONCLUSIÓN: Es importante realizar talleres en el ámbito escolar para reducir los daños a la salud y el Programa de Salud Escolar puede ser un facilitador para el acceso a temas de sexualidad y salud reproductiva.

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Apoptotic signaling pathways are involved in acute kidney injury (AKI) induced by the antineoplastic drug cisplatin (Cis). Mechanical stress is known to increase interleukin (IL) -11, a pleiotropic cytokine with antiapoptotic and antinecrotic effects. We compared the impact of high-intensity interval training (HIIT) with low-intensity continuous training (LICT) and moderate-intensity continuous training (MICT) on renal levels of IL-11 and the expression of apoptotic markers in female rats with nephrotoxicity induced by Cis. For that, the animals were divided into five groups (n = 7): control and sedentary (C + S); Cis and sedentary (Cis + S); Cis and LICT (Cis + LICT); Cis and MICT (Cis + MICT) and Cis and HIIT (Cis + HIIT). At the end of 8 weeks of treadmill running, the rats received a single injection of Cis (5 mg/kg), and 7 days later they were euthanized. Serum and kidney samples were collected to assess the blood urea nitrogen (BUN), gene expression of TNF receptor 1 (TNFR1) and 2 (TNFR2), caspase-3, (p38) MAPK (MAPK14), p53, Bax, Bak, Bcl-2, and Bcl-xL, renal levels of IL-11, IL-8, and p53, and immunolocalization of cleaved caspase-3, Bax, Bcl-2, and (p38) MAPK in renal tissue. Our data indicate that all trained groups showed a significant intensity-dependent increase in renal levels of IL-11 associated with reduced local expression of proapoptotic and increased antiapoptotic markers, but these effects were more pronounced with HIIT. So, HIIT appears to provide superior renoprotection than traditional continuous training by modulating apoptotic signaling pathways, and this effect can be related to the increase in renal levels of IL-11.

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Due to environmental contamination, the environment constantly receives pollutants from various anthropic actions. These pollutants put ecological health at risk due to contamination and accumulation in living organisms, including wild animals and humans. Exposure can cause physiological, morphological, and behavioral changes in living beings. In this context, laboratory studies have frequently investigated how environmental contaminants affect the male reproductive system and gametes. However, few studies have examined how these contaminants affect male reproduction in naturally exposed animals. To better understand this topic, we conducted a systematic review of the effects of exposing male vertebrate animals to polluted environments on their reproductive functions. After an extensive search using the PubMed/MEDLINE, Scopus, and Web of Science databases, 39 studies met our inclusion criteria and were eligible for this review. This study showed that reproductive damages were frequent in fishes, amphibians, reptiles, birds, and mammals exposed to contaminated environments. Wild animals are exposed mainly to endocrine-disrupting compounds (EDCs), toxic metals, and radiation. Exposure to pollutants causes a reduction in androgen levels, impaired spermatogenesis, morphological damage to reproductive organs, and decreased sperm quality, leading to reduced fertility and population decline. Although several species have been studied, the number of studies is limited for some groups of vertebrates. Wildlife has proven valuable to our understanding of the potential effects of environmental contaminants on human and ecosystem health. Thus, some recommendations for future investigations are provided. This review also creates a baseline for the understanding state of the art in reproductive toxicology studies.

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Meplazumab, a humanized CD147 antibody, has shown favourable safety and efficacy in our previous clinical studies. In DEFLECT (NCT04586153), 167 patients with severe COVID-19 were enroled and randomized to receive three dosages of meplazumab and a placebo. Meplazumab at 0.12 mg/kg, compared to the placebo group, showed clinical benefits in significantly reducing mortality by 83.6% (2.4% vs. 14.6%, p = 0.0150), increasing the proportion of patients alive and discharged without supplemental oxygen (82.9% vs. 70.7%, p = 0.0337) and increasing the proportion of patients who achieved sustained clinical improvement (41.5% vs. 31.7%). The response rate in the 0.2 mg/kg group was relatively increased by 16.0% compared with the placebo group (53.7% vs. 46.3%). Meplazumab also reduced the viral loads and multiple cytokine levels. Compare with the placebo group, the 0.3 mg/kg significantly increased the virus negative rate by 40.6% (p = 0.0363) and reduced IL-8 level (p = 0.0460); the 0.2 mg/kg increased the negative conversion rate by 36.9%, and reduced IL-4 (p = 0.0365) and IL-8 levels (p = 0.0484). In this study, the adverse events occurred at a comparable rate across the four groups, with no unexpected safety findings observed. In conclusion, meplazumab promoted COVID-19 convalescence and reduced mortality, viral load, and cytokine levels in severe COVID-19 population with good safety profile.

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ABSTRACT Background: Cases of coronavirus disease 2019 (COVID-19) requiring hospitalization continue to appear in vulnerable populations, highlighting the importance of novel treatments. The hyperinflammatory response underlies the severity of the disease, and targeting this pathway may be useful. Herein, we tested whether immunomodulation focusing on interleukin (IL)-6, IL-17, and IL-2, could improve the clinical outcomes of patients admitted with COVID-19. Methods: This multicenter, open-label, prospective, randomized controlled trial was conducted in Brazil. Sixty hospitalized patients with moderate-to-critical COVID-19 received in addition to standard of care (SOC): IL-17 inhibitor (ixekizumab 80 mg SC/week) 1 dose every 4 weeks; low-dose IL-2 (1.5 million IU per day) for 7 days or until discharge; or indirect IL-6 inhibitor (colchicine) orally (0.5 mg) every 8 hours for 3 days, followed by 4 weeks at 0.5 mg 2x/day; or SOC alone. The primary outcome was accessed in the "per protocol" population as the proportion of patients with clinical improvement, defined as a decrease greater or equal to two points on the World Health Organization's (WHO) seven-category ordinal scale by day 28. Results: All treatments were safe, and the efficacy outcomes did not differ significantly from those of SOC. Interestingly, in the colchicine group, all participants had an improvement of greater or equal to two points on the WHO seven-category ordinal scale and no deaths or patient deterioration were observed. Conclusions: Ixekizumab, colchicine, and IL-2 were demonstrated to be safe but ineffective for COVID-19 treatment. These results must be interpreted cautiously because of the limited sample size.