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In the ongoing fight against Coronavirus Disease 2019 (COVID-19), researchers are exploring potential treatments to improve outcomes, especially in severe cases. This includes investigating the repurposing of existing medications, such as furosemide, which is widely available. This study aimed to evaluate the impact of furosemide on mortality rates among COVID-19 patients with severe or critical illness. We assessed a cohort of 515 hospitalized adults who experienced a high mortality rate of 43.9%. Using a multivariate analysis with adjusted risk ratios (AdRRs), factors like smoking (AdRR 2.48, 95% CI 1.53-4.01, p < 0.001), a high Pneumonia Severity Index (PSI) score (AdRR 7.89, 95% CI 5.82-10.70, p < 0.001), mechanical ventilation (AdRR 23.12, 95% CI 17.28-30.92, p < 0.001), neutrophilia (AdRR 2.12, 95% CI 1.52-2.95, p < 0.001), and an elevated neutrophil-to-lymphocyte ratio (NLR) (AdRR 2.39, 95% CI 1.72-3.32, p < 0.001) were found to increase mortality risk. In contrast, vaccination and furosemide use were associated with reduced mortality risk (AdRR 0.58, p = 0.001 and 0.60, p = 0.008; respectively). Furosemide showed a pronounced survival benefit in patients with less severe disease (PSI < 120) and those not on hemodialysis, with mortality rates significantly lower in furosemide users (3.7% vs. 25.7%). A Kaplan-Meier analysis confirmed longer survival and better oxygenation levels in patients treated with furosemide. Furthermore, a Structure-Activity Relationship analysis revealed that furosemide's sulfonamide groups may interact with cytokine sites such as tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6), potentially explaining its beneficial effects in COVID-19 management. These findings suggest that furosemide could be a beneficial treatment option in certain COVID-19 patient groups, enhancing survival and improving oxygenation.
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BACKGROUND: COVID-19 is an infectious disease caused by SARS-CoV-2. It is unclear whether influenza vaccination reduces the severity of disease symptoms. Previous studies have suggested a beneficial effect of influenza vaccination on the severity of COVID-19. The aim of this study was to evaluate the possible protective effect of the influenza vaccine on the occurrence of SARS-CoV-2 infection symptoms and prognosis in patients hospitalized with COVID-19. METHODS: This was a retrospective cohort study of patients who tested positive for SARS-CoV-2, identified by quantitative real-time polymerase chain reaction. Chi-square tests, Kaplan-Meier analysis, and multivariate analysis were performed to assess the association between influenza vaccination and the presence of symptoms in hospitalized patients with COVID-19 and their outcome. RESULTS: In this study, 1712 patients received positive laboratory tests for SARS-CoV-2; influenza vaccination was a protective factor against the presence of characteristic COVID-19 symptoms such as polypnea, anosmia, dysgeusia, and fever (p < 0.001). Influenza-vaccinated patients had fewer days of hospitalization (p = 0.029). CONCLUSIONS: The findings of this study support that influenza vaccination is associated with a decrease in the number of symptoms in patients hospitalized due to COVID-19, with fewer days of hospitalization, but not with the outcome of disease.
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Endometrial cancer (EC) is a significant cause of cancer-related deaths in women. MicroRNAs (miRs) play a role in cancer development, acting as oncogenes or tumor suppressors. This study evaluated the diagnostic potential of hsa-miR-185-5p and hsa-miR-191-5p in EC and their correlation with clinical and histopathological features. A cross-sectional study analyzed formalin-fixed, paraffin-embedded tissue samples from 59 patients: 18 with EC, 21 with endometrial hyperplasia (EH), 17 with normal endometrium (NE), and 3 with endometrial polyps (EPs). Quantitative reverse transcription-polymerase chain reaction and TaqMan probes were used for miR expression analysis. The Shapiro-Wilk test was used to analyze the normal distribution of the data. Subsequently, parametric or non-parametric tests were used to evaluate the associations between the expression levels of each miR and clinical parameters. Both miRs were underexpressed in some precursor and malignant lesions compared to certain NE subtypes and benign lesions. Specifically, hsa-miR-185-5p showed underexpression in grade 3 EC compared to some NE and EH subtypes (FC: -57.9 to -8.5, p < 0.05), and hsa-miR-191-5p was underexpressed in EH and EC compared to secretory endometrium and EPs (FC: -4.2 to -32.8, p < 0.05). SETD1B, TJP1, and MSI1 were common predicted target genes. In conclusion, hsa-miR-185-5p and hsa-miR-191-5p are underexpressed in EC tissues, correlating with histopathological grades, highlighting their potential as diagnostic biomarkers and their role as tumor suppressors in EC.
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Neoplasias do Endométrio , Endométrio , Regulação Neoplásica da Expressão Gênica , MicroRNAs , Humanos , Feminino , MicroRNAs/genética , MicroRNAs/metabolismo , Neoplasias do Endométrio/genética , Neoplasias do Endométrio/patologia , Neoplasias do Endométrio/metabolismo , Endométrio/metabolismo , Endométrio/patologia , Pessoa de Meia-Idade , Estudos Transversais , Gradação de Tumores , Adulto , Idoso , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismoRESUMO
Vitamin D3 or calcitriol (VitD3) has been shown to have anticancer and anti-inflammatory activity in in vitro models and clinical studies. However, its effect on HPV-16-related cancer has been sparsely explored. In this study, we aimed to determine whether monotherapy or combination therapy with cisplatin (CP) reduces tumor growth and affects survival and systemic inflammation. Treatments were administered to C57BL/6 mice with HPV-16-related tumors (TC-1 cells) as follows: (1) placebo (100 µL vehicle, olive oil, orally administered daily); (2) VitD3 (3.75 µg/kg calcitriol orally administered daily); (3) CP (5 mg/kg intraperitoneally, every 7 days); and (4) VitD3+CP. Tumor growth was monitored for 25 days, survival for 60 days, and the neutrophil-to-lymphocyte ratio (NLR) was evaluated on days 1 (baseline), 7, and 14. VitD3+CP showed greater success in reducing tumor volume compared to CP monotherapy (p = 0.041), while no differences were observed between CP and VitD3 monotherapy (p = 0.671). Furthermore, VitD3+CP prolonged survival compared to CP (p = 0.036) and VitD3 (p = 0.007). Additionally, at day 14 the VitD3 and VitD3+CP groups showed significantly lower NLR values than the CP group (p < 0.05, for both comparisons). Vitamin D3 could be a promising adjuvant in the treatment of cervical cancer or solid tumors and deserves further investigation.
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OBJECTIVES: To analyze the gene variants of the renin-angiotensin-aldosterone system and determine their association with the severity and outcome of COVID-19. METHODS: A total of 104 patients were included in the study: 34 asymptomatic patients with COVID-19 as controls and 70 symptomatic patients as cases. The genetic variants ACE rs4343, ACE2 rs2074192, AGTR1 rs5182, and AGT rs4762 were identified using TaqMan genotyping tests. RESULTS: Patients with the T/T genotype of AGTR1 rs5182 have a higher probability of developing symptomatic COVID-19 (odds ratio [OR] 12.25, 95% confidence interval [CI] 1.34-111.9, P ≤0.001) and a higher risk of hospitalization because of disease (OR 14.00, 95% CI 1.53-128.49, P = 0.012). The haplotype CTG (AGTR1 rs5182, ACE2 rs2074192, ACE rs4343) decreased the odds of death related to COVID-19 in the study population (OR 0.03, 95% CI 0.0-0.06, P = 0.026). CONCLUSIONS: The T/T genotype of the AGTR1 rs5182 variant increased the probability of symptomatic COVID-19 and hospitalization, whereas the haplotype CTG (consisting of AGTR1 rs5182, ACE2 rs2074192, and ACE rs4343) decreased the odds of death related to COVID-19 by 97% in the hospitalized patients with COVID-19. These results support the participation of renin-angiotensin-aldosterone system gene variants as modifiers of the severity of symptoms associated with SARS-CoV-2 infection and the outcome of COVID-19.
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Enzima de Conversão de Angiotensina 2 , COVID-19 , Hospitalização , Peptidil Dipeptidase A , Receptor Tipo 1 de Angiotensina , Sistema Renina-Angiotensina , SARS-CoV-2 , Índice de Gravidade de Doença , Humanos , COVID-19/genética , COVID-19/mortalidade , COVID-19/virologia , Masculino , Feminino , Pessoa de Meia-Idade , Receptor Tipo 1 de Angiotensina/genética , Sistema Renina-Angiotensina/genética , Enzima de Conversão de Angiotensina 2/genética , SARS-CoV-2/genética , Peptidil Dipeptidase A/genética , Adulto , Polimorfismo de Nucleotídeo Único , Idoso , Angiotensinogênio/genética , Genótipo , Predisposição Genética para Doença , Haplótipos , Estudos de Casos e ControlesRESUMO
INTRODUCTION: The interferon pathway plays a critical role in triggering the immune response to SARS-CoV-2, and these gene variants may be involved in the severity of COVID-19. This study aimed to analyze the frequency of three gene variants of OAS and RNASEL with the occurrence of COVID-19 symptoms and disease outcome. METHODS: This cross-sectional study included 104 patients with SARS-CoV-2 infection, of which 34 were asymptomatic COVID-19, and 70 were symptomatic cases. The variants rs486907 (RNASEL), rs10774671 (OAS1), rs1293767 (OAS2), and rs2285932 (OAS3) were screened and discriminated using a predesigned 5'-nuclease assay with TaqMan probes. RESULTS: Patients with the allele C of the OAS2 gene rs1293767 (OR = 0.36, 95% CI: 0.15-0.83, p = 0.014) and allele T of the OAS3 gene rs2285932 (OR = 0.39, 95% CI: 0.2-0.023, p = 0.023) have lower susceptibility to developing symptomatic COVID-19. The genotype frequencies (G/G, G/C, and C/C) of rs1293767 for that comparison were 64.7%, 29.4%, and 5.9% in the asymptomatic group and 95.2%, 4.8%, and 0% in severe disease (p < 0.05). CONCLUSIONS: Our data indicate that individuals carrying the C allele of the OAS2 gene rs1293767 and the T allele of the OAS3 gene rs2285932 are less likely to develop symptomatic COVID-19, suggesting these genetic variations may confer a protective effect among the Mexican study population. Furthermore, the observed differences in genotype frequencies between asymptomatic individuals and those with severe disease emphasize the potential of these variants as markers for disease severity. These insights enhance our understanding of the genetic factors that may influence the course of COVID-19 and underscore the potential for genetic screening in identifying individuals at increased risk for severe disease outcomes.
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The COVID-19 pandemic has had a significant impact on the health and economy of the global population. Even after recovery from the disease, post-COVID-19 symptoms, such as pulmonary fibrosis, continue to be a concern. This narrative review aims to address pulmonary fibrosis (PF) from various perspectives, including the fibrotic mechanisms involved in idiopathic and COVID-19-induced pulmonary fibrosis. On the other hand, we also discuss the current therapeutic drugs in use, as well as those undergoing clinical or preclinical evaluation. Additionally, this article will address various biomarkers with usefulness for PF prediction, diagnosis, treatment, prognosis, and severity assessment in order to provide better treatment strategies for patients with this disease.
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COVID-19 , Fibrose Pulmonar Idiopática , Humanos , Pandemias , COVID-19/complicações , Fibrose Pulmonar Idiopática/diagnóstico , Fibrose Pulmonar Idiopática/tratamento farmacológico , Fibrose Pulmonar Idiopática/etiologia , Fibrose , Biomarcadores , Teste para COVID-19RESUMO
The present study highlighted the repositioning of the drug dapsone (DDS) for cancer therapy. Due to its mechanism of action, DDS has a dual effect as an antibiotic and as an anti-inflammatory/immunomodulator; however, at high doses, it has important adverse effects. The derivative DDS-13 [N,N'-(sulfonyl bis (4,1-phenylene)) dioctanamide] was synthesized through an N-acylation reaction to compare it with DDS. Its cytotoxic effects in cancer cells (DU145 and HeLa) and non-cancer cells (HDFa) were observed at concentrations ranging 0.01-100 µM and its physicochemical/pharmacokinetic properties were analyzed using the SwissADME tool. The objectives of the present study were to evaluate the anticancer activity of both DDS and DDS-13 and to identify the physicochemical and pharmacokinetic properties of DDS-13. The results showed that DDS-13 presented a cytotoxic effect in the DU145 cell line (IC50=19.06 µM), while DDS showed a cytotoxic effect on both the DU145 (IC50=11.11 µM) and HeLa (IC50=13.07 µM) cell lines. DDS-13 appears to be a good cytotoxic candidate for the treatment of prostate cancer, while DDS appears to be a good candidate for both cervical and prostate cancer. Neither candidate showed a cytotoxic effect in non-cancerous cells. The different pharmacokinetic properties of DDS-13 make it a new candidate for evaluation in preclinical models for the treatment of cancer.
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Pre-eclampsia (PE) is a disorder characterized by hypertension in the second trimester of pregnancy that results from abnormal placentation affecting fetal development and maternal health. Previous studies have shown the role of serotonin (5-HT) that leads to poor placental perfusion, where S/S and S/L polymorphisms promote the solute carrier family 6 member 4 (SLC6A4) gene associated with the risk of developing changes in the microvasculature of the placenta. This study looked at the association between the gene variant 5-HTTLPR (serotonin-transporter-linked promoter region) of the SLC6A4 gene and the occurrence of PE. A total of 200 women were included: 100 cases (pregnant with PE) and 100 controls (pregnant without complications). Genotyping of the 5-HTTLPR variant was performed using polymerase chain reaction (PCR). Associations between the presence of the genetic variant of interest and PE and other clinical features were evaluated statistically. The frequencies of S/S, S/L, and L/L genotypes were 32%, 53%, and 15% for the cases and 55%, 25%, and 20% in the control group. Compared to the controls, the genotype frequencies S/S vs. S/L + L/L (recessive model) in the cases group were different (p = 0.002). The S/S genotype decreased the probability of PE (OR = 0.39, 95% IC: 0.22-0.69, p = 0.002) and PE with severity criteria (OR = 0.39, 95% IC: 0.17-0.91, p = 0.045). The 5-HTTLPR gene variant of the SLC6A4 gene modifies the risk of PE development among the studied population.
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Acute lymphoblastic leukemia (ALL) is a hematological disease characterized by the dysfunction of the hematopoietic system that leads to arrest at a specific stage of stem cells development, suppressing the average production of cellular hematologic components. BCP-ALL is a neoplasm of the B-cell lineage progenitor. BCP-ALL is caused and perpetuated by several mechanisms that provide the disease with its tumor potential and genetic and cytological characteristics. These pathological features are used for diagnosis and the prognostication of BCP-ALL. However, most of these paraclinical tools can only be obtained by bone marrow aspiration, which, as it is an invasive study, can delay the diagnosis and follow-up of the disease, in addition to the anesthetic risk it entails for pediatric patients. For this reason, it is crucial to find noninvasive and accessible ways to supply information concerning diagnosis, prognosis, and the monitoring of the disease, such as circulating biomarkers. In oncology, a biomarker is any measurable indicator that demonstrates the presence of malignancy, tumoral behavior, prognosis, or responses to treatments. This review summarizes circulating molecules associated with BCP-ALL with potential diagnostic value, classificatory capacity during monitoring specific clinic features of the disease, and/or capacity to identify each BCP-ALL stage regarding its evolution and outcome of the patients with BCP-ALL. In the same way, we provide and classify biomarkers that may be used in further studies focused on clinical approaches or therapeutic target identification for BCP-ALL.
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PURPOSE: This study aims to develop and evaluate a cost-effective, user-friendly multiplex quantitative real-time polymerase chain reaction (qPCR) method for detecting multiple tick-borne pathogens associated with human and veterinary diseases. METHODS: In silico PCR was performed to design and evaluate primer sequences reported for amplifying Rickettsia spp., Borrelia spp., and Ehrlichia spp. Single and multiplex qPCR assays were then standardized to detect individual pathogens and multiple pathogens in a single reaction. Positive controls were generated to determine the dynamic range of the methods. In the validation phase, a total of 800 samples were screened for the presence of tick-borne pathogens. RESULTS: Identification in a single qPCR reaction (multiplex) of Ehrlichia spp., and Borrelia spp. with a limit of detection of 10 copies and Rickettsia spp. with 100 copies, a PCR efficiency (E) of 90-100% and a coefficient of correlation (R2) of 0.998-0.996 for all pathogens. CONCLUSION: The ability to detect three significant pathogens (Ehrlichia spp., Rickettsia spp., and Borrelia spp.) in a single qPCR reaction offers a significant advantage in the field of molecular diagnostics for tick-borne diseases. This advancement has a profound impact on public health as it facilitates the selection of appropriate treatment protocols, thereby reducing complications associated with disease progression. The streamlined approach provided by this method simplifies the diagnostic process and enables timely intervention, ultimately improving patient outcomes and mitigating the potential risks associated with untreated or misdiagnosed tick-borne infections.
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Borrelia , Rickettsia , Doenças Transmitidas por Carrapatos , Carrapatos , Animais , Humanos , Carrapatos/microbiologia , Reação em Cadeia da Polimerase em Tempo Real , Rickettsia/genética , Ehrlichia/genética , Doenças Transmitidas por Carrapatos/diagnóstico , Doenças Transmitidas por Carrapatos/veterinária , Borrelia/genéticaRESUMO
In developed countries, endometrial cancer (EC) is one of the most common neoplasms of the female reproductive system. MicroRNAs (miRs) are a class of single-stranded noncoding RNA molecules with lengths of 19-25 nucleotides that bind to target messenger RNA (mRNA) to regulate post-transcriptional gene expression. Although there is a large amount of research focused on identifying miRs with a diagnostic, prognostic, or response to treatment capacity in EC, these studies differ in terms of experimental methodology, types of samples used, selection criteria, and results obtained. Hence, there is a large amount of heterogeneous information that makes it difficult to identify potential miR biomarkers. We aimed to summarize the current knowledge on miRs that have been shown to be the most suitable potential markers for EC. We searched PubMed and Google Scholar without date restrictions or filters. We described 138 miRs with potential diagnostic, prognostic, or treatment response potential in EC. Seven diagnostic panels showed higher sensitivity and specificity for the diagnosis of EC than individual miRs. We further identified miRs up- or downregulated depending on the FIGO stage, precursor lesions, and staging after surgery, which provides insight into which miRs are expressed chronologically depending on the disease stage and/or that are modulated depending on the tumor grade based on histopathological evaluation.
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The use of derivatives of natural and synthetic origin has gained attention because of their therapeutic effects against human diseases. Coumarins are one of the most common organic molecules and are used in medicine for their pharmacological and biological effects, such as anti-inflammatory, anticoagulant, antihypertensive, anticonvulsant, antioxidant, antimicrobial, and neuroprotective, among others. In addition, coumarin derivates can modulate signaling pathways that impact several cell processes. The objective of this review is to provide a narrative overview of the use of coumarin-derived compounds as potential therapeutic agents, as it has been shown that substituents on the basic core of coumarin have therapeutic effects against several human diseases and types of cancer, including breast, lung, colorectal, liver, and kidney cancer. In published studies, molecular docking has represented a powerful tool to evaluate and explain how these compounds selectively bind to proteins involved in various cellular processes, leading to specific interactions with a beneficial impact on human health. We also included studies that evaluated molecular interactions to identify potential biological targets with beneficial effects against human diseases.
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Anti-Infecciosos , Antineoplásicos , Neoplasias , Humanos , Simulação de Acoplamento Molecular , Cumarínicos/farmacologia , Neoplasias/tratamento farmacológico , Anti-Infecciosos/farmacologia , Anti-Inflamatórios/uso terapêutico , Antineoplásicos/farmacologiaRESUMO
Inflammatory Bowel Disease (IBD) is a chronic gastrointestinal disorder characterized by periods of activity and remission. IBD includes Crohn's disease (CD) and ulcerative colitis (UC), and even though IBD has not been considered as a heritable disease, there are genetic variants associated with increased risk for the disease. 5-Hydroxytriptamine (5-HT), or serotonin, exerts a wide range of gastrointestinal effects under both normal and pathological conditions. Furthermore, Serotonin Transporter (SERT) coded by Solute Carrier Family 6 Member 4 (SLC6A4) gene (located in the 17q11.1-q12 chromosome), possesses genetic variants, such as Serotonin Transporter Gene Variable Number Tandem Repeat in Intron 2 (STin2-VNTR) and Serotonin-Transporter-linked promoter region (5-HTTLPR), which have an influence over the functionality of SERT in the re-uptake and bioavailability of serotonin. The intestinal microbiota is a crucial actor in normal human gut physiology, exerting effects on serotonin, SERT function, and inflammatory processes. As a consequence of abnormal serotonin signaling and SERT function under these inflammatory processes, the use of selective serotonin re-uptake inhibitors (SSRIs) has been seen to improve disease activity and extraintestinal manifestations, such as depression and anxiety. The aim of this study is to integrate scientific data linking the intestinal microbiota as a regulator of gut serotonin signaling and re-uptake, as well as its role in the pathogenesis of IBD. We performed a narrative review, including a literature search in the PubMed database of both review and original articles (no date restriction), as well as information about the SLC6A4 gene and its genetic variants obtained from the Ensembl website. Scientific evidence from in vitro, in vivo, and clinical trials regarding the use of selective serotonin reuptake inhibitors as an adjuvant therapy in patients with IBD is also discussed. A total of 194 articles were used between reviews, in vivo, in vitro studies, and clinical trials.
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Doenças Inflamatórias Intestinais , Serotonina , Humanos , Proteínas da Membrana Plasmática de Transporte de Serotonina/genética , Disbiose/genética , Doenças Inflamatórias Intestinais/genética , Inibidores Seletivos de Recaptação de Serotonina , ImunidadeRESUMO
The current COVID-19 pandemic has completely changed people's daily routines. This has had a big impact on mental health. In Mexico, medical school authorities are interested in understanding the mental health status of the student population to be able to provide support to students who may need help from a mental health specialist. The aim of this study was to develop a platform comprised of a mobile and web application called Mentali, to be used as an auxiliary tool for the detection of conditions such as anxiety and depression, as well as variations in mood, by analysis of the results of validated inventories. Following the Scrum software development methodology, Python, Dart and PHP programming languages were used for development of the application. This platform was used prospectively with 155 first year students taking part in the human medicine program. After 22 weeks, Mentali enabled the identification of 40 users with positive primary screening for anxiety and/or depression (45% for anxiety, 32.5% for both anxiety and depression, and 22.5% for altered mood). These students were contacted and referred to a psychologist; however, only 26 (65%) accepted psychological support. For all of these students a mental health disorder was confirmed. The results support the use of Mentali for the primary screening of anxiety and depression in young adults, including medical students.
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COVID-19 , Estudantes de Medicina , Adulto Jovem , Humanos , Pandemias/prevenção & controle , Depressão/diagnóstico , Depressão/epidemiologia , Depressão/psicologia , COVID-19/diagnóstico , COVID-19/epidemiologia , Ansiedade/diagnóstico , Ansiedade/epidemiologia , Ansiedade/psicologiaRESUMO
The impact of the COVID-19 health crisis on the mental health of the population requires the implementation of new primary screening strategies of mental health disorders to intervene in a timelier manner, and technology may provide solutions. We aimed to evaluate the usefulness of the mobile app Mentali (version 1.1.2; creators: Jorge Alfonso Solís Galván Sodel Vázquez Reyes, Margarita de la Luz Martínez Fierro, Perla Velasco Elizondo, Idalia Garza Veloz, Alejandro Mauricio González and Claudia Caldera Villalobos, Zacatecas, México) as a primary screening tool for anxiety and depression disorders in medical students and to assess the triggering risk factors. This was a descriptive and longitudinal study and included 155 Mexican medical students. Participants interacted with Mentali for 6 months. The mobile app integrated the Beck anxiety and depression inventories together with a mood module. At the end of the interaction, the students received psychological and psychiatric interventions to confirm their primary diagnoses. Symptoms of moderate/severe anxiety and depression were present in 62.6% and 54.6% of the studied population. When corroborating the diagnoses, Mentali obtained a sensitivity of 100%, 95%, and 43% to classify a mental health disorder, anxiety, and depression, respectively. The most important triggers found were as follows: belonging to a dysfunctional family, being introverted, and having suffered from bullying. The proportion of users with excellent/good mood decreased from 78.7% to 34.4% at the end of the semester, and the proportion of users who claimed to have bad/very bad mood increased from 7.4% to 34.4% at the end of the semester (p < 0.05). Mentali was useful for identifying users with anxiety and/or depression, and as an auxiliary tool to coordinate the provision of specialized interventions, allowing us to increase the proportion of patients who needed psychological care and received it by 30%. The efficacy of Mentali in identifying activities through time with an impact on the mood and mental health of the users was confirmed. Our results support the use of Mentali for the primary screening of mental health disorders in young adults, including medical students.
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The abnormal implantation of the trophoblast during the first trimester of pregnancy precedes the appearance of the clinical manifestations of preeclampsia (PE), which is a hypertensive disorder of pregnancy. In a previous study, which was carried out in a murine model of PE that was induced by NG-nitro-L-arginine methyl ester (L-NAME), we observed that the intravenous administration of fibroblast growth factor 2 (FGF2) had a hypotensive effect, improved the placental weight gain and attenuated the fetal growth restriction, and the morphological findings that were induced by L-NAME in the evaluated tissues were less severe. In this study, we aimed to determine the effect of FGF2 administration on the placental gene expression of the vascular endothelial growth factor (VEGFA), VEGF receptor 2 (VEGFR2), placental growth factor, endoglin (ENG), superoxide dismutase 1 (SOD1), catalase (CAT), thioredoxin (TXN), tumor protein P53 (P53), BCL2 apoptosis regulator, Fas cell surface death receptor (FAS), and caspase 3, in a Sprague Dawley rat PE model, which was induced by L-NAME. The gene expression was determined by a real-time polymerase chain reaction using SYBR green. Taking the vehicle or the L-NAME group as a reference, there was an under expression of placental VEGFA, VEGFR2, ENG, P53, FAS, SOD1, CAT, and TXN genes in the group of L-NAME + FGF2 (p < 0.05). The administration of FGF2 in the murine PE-like model that was induced by L-NAME reduced the effects that were generated by proteinuria and the increased BP, as well as the response of the expression of genes that participate in angiogenesis, apoptosis, and OS. These results have generated valuable information regarding the identification of molecular targets for PE and provide new insights for understanding PE pathogenesis.
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Fator 2 de Crescimento de Fibroblastos , Pré-Eclâmpsia , Animais , Modelos Animais de Doenças , Feminino , Fator 2 de Crescimento de Fibroblastos/farmacologia , Expressão Gênica , Humanos , NG-Nitroarginina Metil Éster/efeitos adversos , Placenta/metabolismo , Fator de Crescimento Placentário/genética , Fator de Crescimento Placentário/metabolismo , Pré-Eclâmpsia/induzido quimicamente , Pré-Eclâmpsia/tratamento farmacológico , Pré-Eclâmpsia/genética , Gravidez , Ratos , Ratos Sprague-Dawley , Superóxido Dismutase-1/genética , Proteína Supressora de Tumor p53/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
Bacterial coinfections, which increase the severity of respiratory viral infections, are frequent causes of mortality in influenza pandemics but have not been well characterized in patients with Coronavirus disease 2019 (COVID-19). Moreover, the association of COVID-19 infection with pulmonary Mycobacterium tuberculosis disease (TB) and concurrent pulmonary fungal infection is not well known. The classification of patients with COVID-19-associated pulmonary aspergillosis (CAPA) using the current definitions for invasive fungal diseases has proven difficult. In this study, we aimed to provide information about three patients with underlying diseases ongoing with COVID-19 and co-infection with pulmonary TB, and with COVID-19-associated pulmonary aspergillosis (CAPA). At the time of hospital admission, each patient presented complications such as decompensated T2DM with diabetic ketoacidosis and/or hypertension. Findings of chest computed tomography and serum galactomannan by radioimmunoassay were useful for classifying them as possible CAPA. One of the three possible CAPA cases was fatal. These three cases are rare and are the first of their kind reported worldwide. The generation of reliable algorithms, early diagnosis, standardization of classification criteria, and the selection of specific and personalized treatments for COVID-19-associated opportunistic infections, including CAPA, are necessary to improve outcomes in these kinds of patients.
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BACKGROUND: Some oral lesions have been described in patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2); the possibility has been raised that the buccal lesions observed in patients with the coronavirus disease 2019 (COVID-19) are due to this virus and the patient's systemic condition. The aim of this review was to integrate the knowledge related to the oral lesions associated with COVID-19 and the participation of the buccal cavity in the establishment of immunity against SARS-CoV-2. METHODS: A literature search on the manifestations of buccal lesions from the beginning of the pandemic until October 2021 was carried out by using the PubMed database. A total of 157 scientific articles were selected from the library, which included case reports and reports of lesions appearing in patients with COVID-19. RESULTS: Oral lesions included erosions, ulcers, vesicles, pustules, plaques, depapillated tongue, and pigmentations, among others. The oral cavity is a conducive environment for the interaction of SARS-CoV-2 with the mucosal immune system and target cells; direct effects of the virus in this cavity worsen the antiviral inflammatory response of underlying oral disorders, immunodeficiencies, and autoimmunity primarily. CONCLUSIONS: The oral cavity is an accessible and privileged environment for the interaction of SARS-CoV-2 with the mucosal immune system and target cells; the direct effects of the virus in this cavity worsen the antiviral inflammatory response of underlying oral disorders, in particular those related to immunodeficiencies and autoimmunity.