Downregulation of Tnf-α and Cat Expression in a Wistar Rat Diabetic Model during Diabetes Onset.

INTRODUCTION: Diabetes Mellitus (DM) is a metabolic disorder characterized by persistent hyperglycemia and/or insulin resistance. If left uncontrolled, it can lead to a combination of cardiac and renal alterations known as cardiorenal syndrome. Additionally, oxidative stress and inflammation contribute to tissue damage, thereby reducing the life expectancy of individuals with diabetes. AIM: The aim of this study was to identify early molecular markers associated with cardiorenal syndrome, oxidative stress, and inflammation, and to investigate their correlation with the duration of exposure to DM. METHODS: An experimental DM model was employed using Wistar rats. The rats were divided into four groups: diabetic rats at 7 days (DM7), diabetic rats at 30 days (DM30), control sham at 7 days (CS7), and control sham at 30 days (CS30). Blood and brain tissue from the brainstem region were collected at 7 and 30 days after confirming DM induction. Gene expression analysis of Bnp, Anp, Cat, Gpx, Sod, Tnf-α, and Il-6 was performed. RESULTS: The analysis revealed lower expression values of Cat in the brainstem tissue of the DM7 group compared to the NDS7 group. Moreover, diabetic animals exhibited statistically lower levels of Tnf-α in their peripheral blood compared to the control animals. CONCLUSION: This study concluded that DM alters the oxidative balance in the brainstem after 7 days of DM induction, resulting in lower Cat expression levels. Although some genes did not show statistical differences after 30 days of DM induction, other genes exhibited no expression values, indicating possible gene silencing. The study identified an imbalance in the studied pathways and concluded that the organism undergoes a compensatory state in response to the initial metabolic alterations caused by DM.

Relationship of irisin expression with metabolic alterations and cardiovascular risk in type 2 diabetes mellitus: a preliminary study.

OBJECTIVE: The aim of this study was to investigate the role of irisin in type 2 diabetes mellitus and its association with metabolic alterations and obesity. METHODS: A cross-sectional case-control study was conducted on participants treated at Centro Universitário FMABC between August 2018 and July 2019, by comparing a control group (n=14) with type 2 diabetes mellitus patients (n=16). The control group consisted of participants aged above 21 years with no chronic diseases, diabetes, smoking, or illicit drug use. The type 2 diabetes mellitus group included patients aged above 21 years, who were diagnosed with type 2 diabetes for at least 5 years (glycated hemoglobin>7%). Exclusion criteria were not willing to continue, recent hospitalization, and failure to meet inclusion criteria. Biochemical parameters included blood glucose, glycated hemoglobin, plasma irisin levels, and irisin gene expression in peripheral blood. RESULTS: Type 2 diabetes mellitus patients exhibited significantly higher plasma glucose levels [143 (40) vs. 92 (13) mg/dL, *p<0.05] and glycated hemoglobin levels [7.1% (1.6) vs. 5.6% (0.5), *p<0.05] compared to the control group. Irisin gene expression in type 2 diabetes mellitus patients was lower 0.02288 (0.08050) than the control group 8.506e-006 (1.412e-005) (p=0.06). Correlation analysis revealed a positive association between irisin expression and body mass index in type 2 diabetes mellitus (Rho=0.5221, 95%CI -0.058 to 0.838, p=0.06), while plasma irisin showed a negative correlation with body mass index (Rho=-0.656, 95%CI -0.836 to 0.215, p=0.03). No significant correlations were found between plasma glucose or glycated hemoglobin levels and irisin expression. CONCLUSION: The data suggests that body mass index directly influences plasma irisin levels and the regulation of irisin gene expression, possibly linking irisin to adiposity changes observed in obesity-related type 2 diabetes mellitus.

Expression of TNFR1, VEGFA, CD147 and MCT1 as early biomarkers of diabetes complications and the impact of aging on this profile.

Hyperglycemia leads to microvascular lesions in various tissues. In diabetic nephropathy-DN, alterations in usual markers reflect an already installed disease. The study of new biomarkers for the early detection of diabetic complications can bring new prevention perspectives. Rats were divided into diabetic adult-DMA-or elderly-DME and control sham adult-CSA-or control sham elderly-CSE. Blood and urine samples were collected for biochemical analysis. Bulbar region, cardiac, hepatic and renal tissues were collected for target gene expression studies. As result, DMA showed decreased TNFR1, MCT1 and CD147 expression in the bulbar region, TNFR1 in the heart, VEGFA and CD147 in the kidney and TNFR1 in blood. Positive correlations were found between TNFR1 and MCT1 in the bulbar region and HbA1c and plasma creatinine, respectively. DME showed positive correlation in the bulbar region between TNFR1 and glycemia, in addition to negative correlations between CD147 in the heart versus glycemia and urea. We concluded that the initial hyperglycemic stimulus already promotes changes in the expression of genes involved in the inflammatory and metabolic pathways, and aging alters this profile. These changes prior to the onset of diseases such as DN, show that they have potential for early biomarkers studies.

Survivin expression as a prognostic marker for breast cancer.

OBJECTIVE: Due to the speed of development observed in breast cancer, several studies aimed at discovering new biomarkers have been carried out in order to arrive at an early diagnosis. As survivin plays a fundamental role in the evasion of apoptosis in tumor cells, the aim of this study was to verify the expression profile of the survivin gene in paraffin-embedded breast tumor samples and associate it with the clinical characteristics of the patients. METHODS: This is a cross-sectional study, for which 100 tumor samples were obtained from cancer patients treated throughout the year 2019 at Instituto de Mama do Cariri (Juazeiro do Norte, in the state of Ceará). This study included women over 30 years old who had confirmed breast cancer through anatomopathological examination but excluded those with non-neoplastic breast comorbidities, other neoplasms, or chronic diseases. Survivin gene expression was assessed by quantitative polymerase chain reaction. RESULTS: The expression of survivin is associated with the lack of expression of estrogen (p=0.027) and progesterone (p>0.0005) receptors. It means that survivin expression is higher in patients in which labeling was absent for estrogen receptor and progesterone receptor. CONCLUSION: Our data reinforce that survivin expression is higher in estrogen receptor-patients, thus representing an additional prognostic tool.

Survivin expression as a prognostic marker for breast cancer

SUMMARY OBJECTIVE: Due to the speed of development observed in breast cancer, several studies aimed at discovering new biomarkers have been carried out in order to arrive at an early diagnosis. As survivin plays a fundamental role in the evasion of apoptosis in tumor cells, the aim of this study was to verify the expression profile of the survivin gene in paraffin-embedded breast tumor samples and associate it with the clinical characteristics of the patients. METHODS: This is a cross-sectional study, for which 100 tumor samples were obtained from cancer patients treated throughout the year 2019 at Instituto de Mama do Cariri (Juazeiro do Norte, in the state of Ceará). This study included women over 30 years old who had confirmed breast cancer through anatomopathological examination but excluded those with non-neoplastic breast comorbidities, other neoplasms, or chronic diseases. Survivin gene expression was assessed by quantitative polymerase chain reaction. RESULTS: The expression of survivin is associated with the lack of expression of estrogen (p=0.027) and progesterone (p>0.0005) receptors. It means that survivin expression is higher in patients in which labeling was absent for estrogen receptor and progesterone receptor. CONCLUSION: Our data reinforce that survivin expression is higher in estrogen receptor-patients, thus representing an additional prognostic tool.

Preclinical Effects Of Melatonin On The Development Of Ehrlich's Tumor: A Biochemical, Cognitive, And Molecular Approach.

BACKGROUND: It has already been shown that melatonin is an antitumoral molecule that affects malignant cells via some mechanisms. The benefit played by this hormone on cancer is due to its antioxidant effects. OBJECTIVE: This study aimed to evaluate the preclinical effects of melatonin in mice with the Ehrlich ascites tumor. METHODS: Twenty Balb/ c male mice with Ehrlich tumor were treated with different melatonin doses. Their inflammatory and oxidative stress were accessed by gene expression. Hepatotoxicity and hematological parameters were also evaluated through biochemical analyses. Animal welfare was analysed weekly from the categories guided by the NC3Rs. RESULTS: Gene expression analyses have shown that only Tnfα and Sod1 were expressed in all groups studied. Only the M-3 group showed increased Tnfα expression compared to the control. All groups treated with melatonin showed decreased Sod1 expression compared to the control. No signs of hepatotoxicity were caused by any of the melatonin doses used in the treatment. CONCLUSION: In animals with Ehrlich´s tumor treated with melatonin, a decrease in oxidative stress, an amelioration in welfare and in cognitive tasks could be observed, even if the treatment has not reduced the size of the tumor itself. In parallel with the already patented use of melatonin in the treatment of sleep disorders or chronic kidney disease, our results propose its use to improve the general well-being of breast cancer patients.

Quantification of Vitamin D at Different Levels of Clinical Worsening of COVID-19.

INTRODUCTION AND AIM: Vitamin D is the name given to a group of lipid-soluble steroidal substances of physiological importance in the body, especially in bone metabolism. The active form of vitamin D is believed to have immunomodulatory effects on immune system cells, especially T lymphocytes, as well as on the production and action of several cytokines and on the expression of potent antimicrobial peptides in epithelial cells that line the respiratory tract, playing an important role in protecting the lung from infections. The aim of this study was to assess vitamin D levels in patients with COVID-19 in healthcare service and to verify that these levels are adequate to protect the progression of this infection. METHODS: The aim of this observational study was to evaluate the serum concentration of vitamin D in 300 patients suspected of being infected with COVID-19, treated at Basic Health Units (BHUs) and at the Hospital Complex in the municipality of São Bernardo do Campo. RESULTS: 294 patients were included, 195 (66%) of which tested positive for COVID-19 and 99 (34%) negative for COVID-19. Among the patients in the positive group, 163 patients were in the mild group (84%); 22 patients in the moderate group (11%); 8 patients in the severe group (4%), and 2 patients in the deceased group (1%). CONCLUSION: For the patients in this study, no association was observed for the protective factor of vitamin D against COVID-19 infection, and its role in controlling the clinical staging of the disease was not verified.

Relationship of irisin expression with metabolic alterations and cardiovascular risk in type 2 diabetes mellitus: a preliminary study

SUMMARY OBJECTIVE: The aim of this study was to investigate the role of irisin in type 2 diabetes mellitus and its association with metabolic alterations and obesity. METHODS: A cross-sectional case-control study was conducted on participants treated at Centro Universitário FMABC between August 2018 and July 2019, by comparing a control group (n=14) with type 2 diabetes mellitus patients (n=16). The control group consisted of participants aged above 21 years with no chronic diseases, diabetes, smoking, or illicit drug use. The type 2 diabetes mellitus group included patients aged above 21 years, who were diagnosed with type 2 diabetes for at least 5 years (glycated hemoglobin>7%). Exclusion criteria were not willing to continue, recent hospitalization, and failure to meet inclusion criteria. Biochemical parameters included blood glucose, glycated hemoglobin, plasma irisin levels, and irisin gene expression in peripheral blood. RESULTS: Type 2 diabetes mellitus patients exhibited significantly higher plasma glucose levels [143 (40) vs. 92 (13) mg/dL, *p<0.05] and glycated hemoglobin levels [7.1% (1.6) vs. 5.6% (0.5), *p<0.05] compared to the control group. Irisin gene expression in type 2 diabetes mellitus patients was lower 0.02288 (0.08050) than the control group 8.506e-006 (1.412e-005) (p=0.06). Correlation analysis revealed a positive association between irisin expression and body mass index in type 2 diabetes mellitus (Rho=0.5221, 95%CI -0.058 to 0.838, p=0.06), while plasma irisin showed a negative correlation with body mass index (Rho=-0.656, 95%CI -0.836 to 0.215, p=0.03). No significant correlations were found between plasma glucose or glycated hemoglobin levels and irisin expression. CONCLUSION: The data suggests that body mass index directly influences plasma irisin levels and the regulation of irisin gene expression, possibly linking irisin to adiposity changes observed in obesity-related type 2 diabetes mellitus.

INCISIONAL HERNIA AFTER BARIATRIC SURGERY: ONLY THE PHYSICAL EXAMINATION IS ENOUGH?

BACKGROUND: Incisional hernia is characterized by a bulging of the abdominal wall caused by the prolapse of intracavitary structures, such as a segment of the small intestine, through the trocar orifice. Ultrasonography and physical examination are used in the diagnosis of incisional hernia. AIMS: This study aimed to evaluate the difference between physical examination and abdominal ultrasonography at the diagnosis of incisional hernia in patients who underwent laparoscopic bariatric surgery. METHODS: A total of 123 patients who underwent Roux-en-Y gastric bypass type bariatric surgery performed by laparoscopy were analyzed for the presence or absence of hernia by physical and ultrasonography examination at each trocar incision site. RESULTS: In our results, a total of 7 hernias were detected by physical examination, while ultrasonography detected a total of 56 hernias in at least one of the incision sites. Lin's concordance analysis showed that the tests are not concordant. The association between body mass index and hernia detection (p=0.04 for physical examination and p=0.052 for ultrasonography) was observed. Ultrasonography detected more incisional hernias in 10-mm or larger trocars than in 5-mm trocars (p<0.0001, p<0.05). No differences were noted among the trocar types that were used. CONCLUSIONS: Abdominal ultrasonography showed to have a higher accuracy than physical examination, resulting in a substantial increase in incisional hernia detection at the trocar sites.

Comparative Study on the Effects of Paullinia cupana, PC-18 and Magnesium Chloride on Solid Ehrlich Tumor.

New perspectives arise in the therapeutic practice for cancer, with the objective to not only treat patients, but also improve their quality of life. Guarana, a plant from Brazilian Amazon presents a wide range of pharmacological actions. This study evaluated the effect of Guarana (Paullinia cupana) extract, pure and dry Guarana (PC-18) extract and magnesium chloride (MgCl2) in mice of the Balb/c strain inoculated with the Ehrlich tumor regarding gene expression of inflammatory markers transforming growth factor-ß1 and tumor necrosis factor alpha and oxidative stress (OS) and fatigue, superoxide dismutase, catalase, and glutathione peroxidase 4 and analyzed myelotoxicity and hepatotoxicity. After euthanasia, blood was collected to analyze the complete blood count and measured the levels of liver enzymes (alanine aminotransferase and aspartate aminotransferase). Hepatoprotective actions of the crude extract of P. cupana and PC-18 extract were noticed. The PC-18 and MgCl2 group showed the best result regarding animal welfare. There were no associations between compounds and gene expression regarding fatigue and OS. PC-18 reduced the tumor and may have an antitumor action. The crude extract of Guarana presented hepatoprotective action.

Magnesium Supplementation: Effect on the Expression of Inflammation Genes in Erlich's Tumor.

Magnesium supplementation may be beneficial for cancer patients due to its action as a modulator of cell proliferation and metabolism and its anti-inflammatory effect. Tumor metabolism can influence the bioavailability and absorption of nutrients, leading to an increase in the individual's nutritional needs. In this work, the effects of supplementing different dosages of magnesium chloride in mice with solid Ehrlich's tumors were investigated by analyzing their hematological, inflammatory and anthropometric biomarkers. Three dosages of magnesium chloride (MgCl2) were administered for 28 consecutive days. Animal welfare was assessed according to the criteria stipulated by the National Center for the Replacement, Refinement, and Reduction of Animals in Research (NC3Rs). The inverted grid method was used to analyze muscle strength and fatigue. Difference in expression of the Tumor Necrosis Factor (TNF-α) and the Growth Transformation Factor (TGF-ß1) genes was determined by the 2-ΔCt method. The hematological evaluation consisted of the erythrogram, white blood cell and platelet counts were used for the hematological evaluation and treatment cytotoxicity. Difference in the expression of the TNF-α and TGF-ß genes showed that the group that received a high dose of magnesium had a decrease in TNF-α and RNL, an improvement in well-being with a tendency to increase muscle strength and less tumor progression according to the days of treatment. The group that received a low dosage of magnesium had a smaller tumor volume and a more controlled tumor growth according to the days. The group that received an intermediate dosage presented cytotoxicity.

Incisional hernia after bariatric surgery: only the physical examination is enough? / Hérnia incisional após a cirurgia bariátrica: apenas o exame físico é suficiente?

ABSTRACT BACKGROUND: Incisional hernia is characterized by a bulging of the abdominal wall caused by the prolapse of intracavitary structures, such as a segment of the small intestine, through the trocar orifice. Ultrasonography and physical examination are used in the diagnosis of incisional hernia. AIMS: This study aimed to evaluate the difference between physical examination and abdominal ultrasonography at the diagnosis of incisional hernia in patients who underwent laparoscopic bariatric surgery. METHODS: A total of 123 patients who underwent Roux-en-Y gastric bypass type bariatric surgery performed by laparoscopy were analyzed for the presence or absence of hernia by physical and ultrasonography examination at each trocar incision site. RESULTS: In our results, a total of 7 hernias were detected by physical examination, while ultrasonography detected a total of 56 hernias in at least one of the incision sites. Lin's concordance analysis showed that the tests are not concordant. The association between body mass index and hernia detection (p=0.04 for physical examination and p=0.052 for ultrasonography) was observed. Ultrasonography detected more incisional hernias in 10-mm or larger trocars than in 5-mm trocars (p<0.0001, p<0.05). No differences were noted among the trocar types that were used. CONCLUSIONS: Abdominal ultrasonography showed to have a higher accuracy than physical examination, resulting in a substantial increase in incisional hernia detection at the trocar sites.

RESUMO RACIONAL: A hérnia incisional é caracterizada por um abaulamento da parede abdominal causada por um prolapso das estruturas intracavitárias, como um segmento do intestino delgado, através de um orifício de trocarte. A ultrassonografia e o exame físico são usados no diagnóstico da hérnia incisional. OBJETIVOS: Avaliar a diferença entre o exame físico e a ultrassonografia abdominal no diagnóstico da hérnia incisional em pacientes submetidos a cirurgia bariátrica por videolaparoscopia. MÉTODOS: O total de 123 pacientes submetidos à cirurgia bariátrica, tipo derivação gástrica em Y de Roux, foram avaliados para a presença ou ausência de hérnia incisional por exame físico e ultrassonografia, nos sítios incisionais de cada trocarte. RESULTADOS: O total de sete hérnias foram detectados por exame físico, enquanto a ultrassonografia detectou um total de 56 hérnias em pelo menos um sítio incisional. A análise de concordância de Lin mostrou que os testes empregados não são concordantes. A associação entre o Índice de Massa Corpórea e a detecção de hérnia foi observada (p=0.04, para exame físico, p=0.052 para ultrassonografia). A ultrassonografia detectou mais hérnias incisionais em trocartes de 10 mm ou mais do que em trocartes de 5 mm (p<0,0001, p<0.05). Não foi observada diferença entre os tipos de trocartes empregados. CONCLUSÕES: A ultrassonografia abdominal demonstrou ter acurácia mais elevada que o exame físico, resultando em um aumento substancial na detecção de hérnia incisional nos locais de inserção dos trocartes.

The influence of social isolation on the incidence of positivity in COVID-19 tests in a metropolitan region of São Paulo, Brazil / A influência do isolamento social na incidência de positividade nos testes de COVID-19 em região metropolitana de São Paulo, Brasil

INTRODUCTION: With the arrival of the SARS-CoV-2 (Coronavirus 2 of severe acute respiratory syndrome) pandemic in Brazil, especially in the city of São Paulo, there was a need to apply social isolation policies associated with testing, covering all municipalities. The Clinical Analysis Laboratory of Centro Universitário FMABC was one of the first laboratories to receive certification and qualification to perform RT-PCR (reverse transcriptase reaction followed by polymerase chain reaction) tests in the metropolitan region of São Paulo OBJECTIVE: Aim to analyze the influence of adopting social isolation on the incidence of positivity in COVID-19 tests in the metropolitan region of São Paulo, Brazil METHODS: a descriptive study carried out from March to May 2020, epidemiological data were collected from each unit served and organized by the data controllership team of the Clinical Analysis Laboratory of FMABC. Epidemiological, demographic, and laboratory data were extracted from the Matrix® outpatient data management system. Clinically suspected cases and confirmed by laboratory tests (RT-PCR and serological tests) were entered. The tests were divided into serological tests using the RT-PCR molecular test, on samples of nasopharyngeal mucosal scrapings collected with sterile Swab RESULTS: It were evaluated PCR test and antibody presence (IgA, IgM and IgG) in blood samples of 16.297 patients. 22.718 tests were performed for the diagnosis of COVID-19, both RT-PCR (10.410 tests) and serological tests to detect anti-SARS-CoV-2 antibodies, IgA, IgM and IgG, a total of 16.297 patients were assessed, 63% women and 37% men. It was observed that the social isolation policies adopted during this period contained the massive expansion of contamination, at least while the social isolation rates were above 55% CONCLUSION: The data of this study demonstrated the effectiveness of social isolation in containing the positive contamination of SARS-CoV-2 in the metropolitan region of São Paulo, at least for the first three months

INTRODUÇÃO: com a chegada da pandemia de SARS-CoV-2 (Coronavirus 2 da síndrome respiratória aguda grave) ao Brasil, especialmente na cidade de São Paulo, houve a necessidade de aplicar medidas de distanciamento social associado a testagem, que abrangesse todos os municípios. A região metropolitana de São Paulo compreende 39 municípios e possui uma rede de laboratórios habilitados a realizar a testagem para a detecção do coronavírus, tanto testes sorológicos quanto moleculares. O Laboratório de Análises Clínicas do Centro Universitário ABC/FMABC foi um dos primeiros laboratórios a receber a certificação e habilitação para realizar os testes RT-PCR (reação da transcriptase reversa seguida pela reação em cadeia da polimerase) na região metropolitana de São Paulo OBJETIVO: analisar a influência da adoção do isolamento social na incidência de positividade nos testes de COVID-19 em região metropolitana de São Paulo, Brasil MÉTODO: estudo descritivo realizado no período de março a maio de 2020, os dados epidemiológicos foram coletados de cada unidade atendida e organizada pela equipe de controladoria de dados do Laboratório de Análises Clínicas da FMABC. Os dados epidemiológicos, demográficos e laboratoriais foram extraídos do sistema Matrix® de gerenciamento de dados ambulatoriais. Foram inseridos os casos clinicamente suspeitos e confirmados por testes de laboratório (RT-PCR e testes sorológicos). Os testes foram divididos em testes sorológicos no teste molecular RT-PCR, em amostras de raspado de mucosa nasofaríngea coletada com Swab estéril RESULTADOS: foram avaliados o teste de RT-PCR e a presença de anticorpos (IgA, IgM e IgG) em amostras de sangue de 16.297 pacientes. Foram realizados 22.718 testes para o diagnóstico de COVID-19, tanto RT-PCR (10.410 testes), quanto testes sorológicos para detecção de anticorpos anti-SARS-CoV-2, IgA, IgM e IgG, um total de 16.297 pacientes foram avaliados, 63% mulheres e 37% homens. Observou-se que as políticas de isolamento social adotadas nesse período continham a expansão massiva da contaminação, pelo menos enquanto as taxas de isolamento social eram superiores a 55% CONCLUSÃO: nossos dados demonstraram a efetividade do isolamento social na retenção da positividade da contaminação do SARS-CoV-2 nas cidades contempladas pelo serviço de testagem do Centro Universitário Saúde ABC, pelo menos nos três primeiros meses

Does nebivolol have renoprotective action in patients with chronic kidney disease conditions? An integrative review.

Systemic arterial hypertension (SAH) is a chronic disease of multifactorial origin and one of the main risk factors for major adverse cardiovascular events (MACE), which are the leading causes of morbidity and mortality worldwide. The pharmacological treatment of SAH involves five main classes of drugs, and Nebivolol (NEB) is one of those drugs, belonging to the class of third generation ß1-adrenoceptors selective blockers. NEB is composed of a racemic mixture of two enantiomers: d-nebivolol, which exerts antagonist effects on ß1-adrenoceptors, and l-nebivolol, a vascular ß3 receptor agonist. There are several studies that report different actions of NEB, not only for the treatment of SAH, but also as an antioxidant agent or even as a protector of renal damage. The aim of this systematic review was to investigate the available evidence regarding the effects of NEB on kidney diseases, evaluating its possible renoprotective action.

Kidney Diseases: The Age of Molecular Markers.

Kidney diseases are conditions that increase the morbidity and mortality of those afflicted. Diagnosis of these conditions is based on parameters such as the glomerular filtration rate (GFR), measurement of serum and urinary creatinine levels and equations derived from these measurements (Wasung, Chawla, Madero. Clin Chim Acta 438:350-357, 2015). However, serum creatinine as a marker for measuring renal dysfunction has its limitations since it is altered in several other physiological situations, such as in patients with muscle loss, after intense physical exercise or in people on a high protein diet (Riley, Powers, Welch. Res Q Exerc Sport 52(3):339-347, 1981; Juraschek, Appel, Anderson, Miller. Am J Kidney Dis 61(4):547-554, 2013). Besides the fact that serum creatinine is a marker that indicates glomerular damage, it is necessary the discovery of new biomarkers that reflect not only glomerular damage but also tubular impairment. Recent advances in Molecular Biology have led to the generation or identification of new biomarkers for kidney diseases such as: Acute Kidney Failure (AKI), chronic kidney disease (CKD), nephritis or nephrotic syndrome. There are recent markers that have been used to aid in diagnosis and have been shown to be more sensitive and specific than classical markers, such as neutrophil gelatinase associated lipocalin (NGAL) or kidney injury molecule-1 (KIM-1) (Wasung, Chawla, Madero. Clin Chim Acta 438:350-357, 2015; George, Gounden. Adv Clin Chem 88:91-119, 2019; Han, Bailly, Abichandani, Thadhani, Bonventre. Kidney Int 62(1):237-244, 2002; Fontanilla, Han. Expert Opin Med Diagn 5(2):161-173, 2011). However, early diagnostic biomarkers are still necessary to assist the intervention and monitor of the progression of these conditions.

Ixazomib, an oral proteasome inhibitor, exhibits potential effect in dystrophin-deficient mdx mice.

Dystrophin deficiency makes the sarcolemma fragile and susceptible to degeneration in Duchenne muscular dystrophy. The proteasome is a multimeric protease complex and is central to the regulation of cellular proteins. Previous studies have shown that proteasome inhibition improved pathological changes in mdx mice. Ixazomib is the first oral proteasome inhibitor used as a therapy in multiple myeloma. This study investigated the effects of ixazomib on the dystrophic muscle of mdx mice. MDX mice were treated with ixazomib (7.5 mg/kg/wk by gavage) or 0.2 mL of saline for 12 weeks. The Kondziela test was performed to measure muscle strength. The tibialis anterior (TA) and diaphragm (DIA) muscles were used for morphological analysis, and blood samples were collected for biochemical measurement. We observed maintenance of the muscle strength in the animals treated with ixazomib. Treatment with ixazomib had no toxic effect on the mdx mouse. The morphological analysis showed a reduction in the inflammatory area and fibres with central nuclei in the TA and DIA muscles and an increase in the number of fibres with a diameter of 20 µm2 in the DIA muscle after treatment with ixazomib. There was an increase in the expression of dystrophin and utrophin in the TA and DIA muscles and a reduction in the expression of osteopontin and TGF-ß in the DIA muscle of mdx mice treated with ixazomib. Ixazomib was thus shown to increase the expression of dystrophin and utrophin associated with improved pathological and functional changes in the dystrophic muscles of mdx mice.

Salivary Microbiological and Gingival Health Status Evaluation of Adolescents With Overweight and Obesity: A Cluster Analysis.

Given the high prevalence of obesity in children and adolescents, the investigation of early markers is of clinical importance to better manage this condition. Thus, the aim was to evaluate the cross-sectional relationship between salivary microbiota, gingival health status, and excess weight in adolescents. A total of 248 students (14-17 y; 119 girls) were included, free of caries lesions and periodontal pockets. Physical examination included measures of height, weight, and body fat percentage (%BF). Oral examination was performed to gather information on dental (DMFT index) and gingival health status. Unstimulated saliva was submitted to qPCR reactions to quantify Streptococcus mutans, Porphyromonas gingivalis, Bifidobacteria, and Streptococcus pneumoniae percentages and the NFKappaB expression. Two-way ANOVA was applied considering group (normal-weight/overweight/obesity) and sex factors, in addition to cluster analysis. Group effect was significant for %S. mutans (partial eta2 = 0.20; p < 0.001) and %Bifidobacteria (partial eta2 = 0.19; p < 0.001), with overweight and obesity groups showing the highest levels compared to normal-weight ones, with no significant sex effect. There was no difference in the frequency of gingivitis, P. gingivalis, and S. pneumoniae percentages or NFKappaB expression between groups. Cluster analysis generated three clusters according to body fat accumulation: "Higher %BF," "Moderate %BF," and "Lower %BF." "Higher %BF" cluster was characterized by higher body fat percentage and higher salivary %Bifidobacteria, while cluster "Lower %BF" was characterized by lower body fat percentage and lower frequency of gingivitis ("Moderate %BF" cluster was the contrast). According to nutritional status, a difference in salivary S. mutans and Bifidobacteria percentages was found, with overweight or obesity adolescents showing the highest percentages than normal-weight ones. Besides, a positive relationship between body fat accumulation and Bifidobacteria count was observed, indicating a possible interaction between oral bacteria communities and weight gain.

Involvement of repair genes in oral cancer: A systematic review.

Among the types of cancers that may occur in the oral cavity, squamous cell carcinomas (SCC) of the mouth have a higher incidence and are associated with increased rates of morbidity and mortality. Among steps from the beginning to the progression of the tumour, DNA Repair System is highlighted. The present study aims to conduct a systematic review of the literature on the expression of the repair genes hMSH2 and hMSH6 in patients with SCC in the mouth and oropharyngeal region. The search was performed in databases such as PubMed, Lilacs, and Scielo and included articles published in English from 1999 until 2015. The search in the above-mentioned databases initially yielded 15 scientific articles related to the proposed objective. After a detailed analysis of each of them, only 8 were included in the present review, precisely because they met the inclusion criteria determined in the method. All the reviewed works were unanimous in recognizing the veracity and complexity of the Genomic Repair System, also called Mismatch Repair System, confirming the participation of repair gene proteins (such as hMSH2 and hMSH6) in patients with oral cancer and even of lesions that are susceptible to malignization. SIGNIFICANCE OF THE STUDY: Worldwide, there are an estimated 300 thousand new cases of oral cancer per year. Studies have shown a greater risk in individuals who are smokers and alcohol consumers in developing mouth cancer. Many steps are observed from the beginning to the progression of the tumour, highlighted among them is the moment in which genetic, and epigenetic alterations will interfere in the functioning of the DNA Repair System. This work presents a survey of current knowledge about the involvement of repair genes, especially those of the MutSα system, in the development and progression of oral cancer.

Role of hypoxia-inducible factor 1α as a potential biomarker for renal diseases-A systematic review.

Renal cells need oxygen for homeostasis; it is known for adjusting cellular functioning and the energy obtainment have a broad relationship with cellular respiration, through the O2 bioavailability. O2 homeostasis regulation in the kidney is mediated by hypoxia-inducible factors (HIFs). HIF is divided into three α isoforms, represented by HIF-1α, HIF-2α, and HIF-3α in addition to three paralogs of HIF-1ß; these are involved in some metabolic processes, as well as in the pathogenesis of several diseases. Renal biopsy analyses of patients and experimental animal models aim to understand the relationship between HIF and protection against developing renal diseases or the induction of their onset, being thus this molecule can be considered a potential biomarker of renal disease. We carried out a systematic review to which we included studies on HIF-1α and renal disease in the last 5 years (2013-2018) in researches with humans and/or animal model through searches in three databases: LILACS, PubMed, and SciELO by two researchers. We obtained 22 articles that discussed the relationship with HIF as inductor or protector against renal disease and no relation between HIF and renal. We observed controversies remain regarding the relation between of HIF with renal diseases; this may be related to the different intracellular pathways mediated by HIF-1α, thereby determining differentiated cellular responses.