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.

Ophthalmic Manifestations Among Patients Surviving COVID-19.

Background and Aim: To identify ocular findings related to SARS-CoV-2 infection in patients after the resolution of COVID-19 using complete ocular examinations and optical coherence tomography (OCT). Methods: In this cross-sectional study, conducted from May 30 to October 30, 2020, patients who recovered from various stages COVID-19 underwent eye examination and multimodal retinal imaging (Retinographies and Spectral-OCT). Results: We included 50 patients, 29 (58%) males, median age of 46.5 [standard deviation 15.8]. Of these, 42% (21) had mild, 18% (9) had severe and 40% (20) had critical disease. The median time interquartile range (IQR) between symptom onset and ocular examination was 55 days [IQR 39-71]. Seven patients (14%) reported ophthalmic symptoms, transitory low visual acuity (6%) and retroocular pain (8%). On OCT, one patient without comorbidities had sectoral retinal pallor suggestive of acute retinal ischaemia and oedema of the retina's inner layers and atrophy. All findings progressively and spontaneously improved months after resolution of COVID-19. Conclusion: Patients with COVID-19 present findings compatible with the general population depending on age and comorbidities; nevertheless, acute retinal findings associated with the disease may be present, such as caused either by the direct effects of retinal SARS-CoV-2 infection, by indirect effects of the cytokine storm or by the pro-thrombotic state associated with COVID-19. Therefore, retinal involvement in patients with COVID-19 remains subject to considerable discussion and study.

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.

Use of Saliva to Assess the Adherence to Treatment with Oral Hypoglycemic Agents in Patients with Type 2 Diabetes.

BACKGROUND: The diagnosis of Type 2 Diabetes Mellitus (T2DM) is made by demonstrating the hypoglycemic condition, which involves the determination of plasma glucose, and the follow-up of hypoglycemic treatment is performed by assessing the glycated hemoglobin (HbA1c) concentration. AIM: The aim of this study was to evaluate the saliva as an alternative sample in assessing the adherence to treatment with oral hypoglycemic agents in patients with Type 2 Diabetes. METHODS: We selected 68 patients with T2DM, who were subjected to venous blood and saliva collection, in addition to answering a standardized questionnaire on adherence to hypoglycemic treatment. Laboratory tests performed on saliva, whole blood, serum or plasma included assessment of glycemia, urea, creatinine, uric acid, total cholesterol, HDL-cholesterol, LDL-cholesterol, VLDL-cholesterol, and glycated hemoglobin. RESULTS: It was concluded that 82% of the patients adhered to hypoglycemic treatment based on glycated hemoglobin concentration (cut-off value of 7.0%). Comparing the groups that adhered to hypoglycemic treatment and those that did not adhere, statistical differences (P<0.05) were observed in the glucose, HDL-cholesterol, triglycerides, and insulin use (insulin therapy) parameters. Plasma glucose and urea serum concentration showed positive correlations when compared to saliva samples. Regarding the questionnaire, it was found that 35% of the patients presented positive screening for belief barriers and 83% positive score for recall barriers, and the positive screening correlated with glycated hemoglobin. CONCLUSION: Data have shown that it is possible to use saliva as an alternative sample to the laboratory assessment of hypoglycemic treatment adherence in T2DM 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.

COVID-19 compromises iron homeostasis: Transferrin as a target of investigation.

IMPORTANCE: Since the beginning of the COVID-19 pandemic, numerous metabolic alterations have been observed in individuals with this disease. It is known that SARS-CoV-2 can mimic the action of hepcidin, altering intracellular iron metabolism, but gaps remain in the understanding of possible outcomes in other pathways involved in the iron cycle. OBJECTIVE: To profile iron, ferritin and hepcidin levels and transferrin receptor gene expression in patients diagnosed with COVID-19 between June 2020 and September 2020. DESIGN, SETTING AND PARTICIPANTS: Cross-sectional study that evaluated iron metabolism markers in 427 participants, 218 with COVID-19 and 209 without the disease. EXPOSURES: The primary exposure was positive diagnose to COVID-19 in general population of Santo André and São Bernardo cities. The positive and negative diagnose were determinate through RT-qPCR. MAIN OUTCOMES AND MEASURES: Devido a evidências de alterações do ciclo do ferro em pacientes diagnosticados com COVID-19 e devido a corregulação entre hepcidina e receptor de transferrina, uma análise da expressão gênica deste último, poderia trazer insights sobre o estado de ferro celular. A hipótese foi confirmada, mostrando aumento da expressão de receptor de transferrina concomitante com redução do nível de hepcidina circulante. RESULTS: Serum iron presented lower values in individuals diagnosed with COVID-19, whereas serum ferritin presented much higher values in infected patients. Elderly subjects had lower serum iron levels and higher ferritin levels, and men with COVID-19 had higher ferritin values than women. Serum hepcidin was lower in the COVID-19 patient group and transferrin receptor gene expression was higher in the infected patient group compared to controls. CONCLUSIONS AND RELEVANCE: COVID-19 causes changes in several iron cycle pathways, with iron and ferritin levels being markers that reflect the state and evolution of infection, as well as the prognosis of the disease. The increased expression of the transferrin receptor gene suggests increased iron internalization and the mimicry of hepcidin action by SARS-CoV-2, reduces iron export via ferroportin, which would explain the low circulating levels of iron by intracellular trapping.

Effect of Subchronic Selenium Treatment in the Liver of BALB/C Mice with Transplantable Ehrlich Tumor.

Selenium has an anti-inflammatory, antioxidant, and possibly antitumoral action. Thus, we hypothesized that this element could be an ally in cancer treatment. We evaluated the effect of chelated selenium treatment of BALB/c mice with Erhlich Tumor on tumor size, histology, and biochemical parameters of the liver. A total of 96 male mice were treated for 7, 15, and 30 days with different doses of chelated selenium. During the 7 days of treatment, livers presented mild hydropic degeneration; after 15 days, the livers presented mild hydropic degeneration, inflammatory infiltrate, and steatosis, which was intensified in the animals treated for 30 days. Biochemical analysis showed an increase of the alanine transaminase enzyme in those animals, indicating hepatotoxicity. At the beginning of treatment, selenium was able to inhibit tumor growth. After 30 days of treatment, however, hepatotoxicity could be seen.

Relationship between Lifestyle and Residence Area with 25(OH)D Levels in Older Adults.

The aim of this study was to investigate whether the habitat of older adults living in the urban and rural areas is a contributing factor to altered serum 25(OH)D levels. An analytical, cross-sectional research with a quantitative approach was conducted in the upper backwoods of Paraíba with older adults registered at the Reference Center for Social Assistance (CRAS), addressing residents of both rural area (n = 41) and urban area (n = 43) who were randomly chosen to participate in the study. Data collection took place between January and February 2020. Higher rates of handgrip strength were observed in rural older adults (29.22 ± 8.92 Kgf) with serum 25(OH)D levels in the range of 30 to 40 ng/mL when compared to older adults with concentrations below 30 ng/mL (21.82 ± 5.00 Kgf) and above 40 ng/mL (23.47 ± 6.88 Kgf). Older people living in the urban area, with 25(OH)D levels above 40 ng/mL, presented a lower muscle power index when compared to individuals with vitamin levels from 21 to 29 ng/mL (17.40 ± 6.34 s; 15.33 ± 2.00 s). The urbanization associated with 25(OH)D levels can cause changes in skeletal and respiratory muscle strength, because the habitat associated with 25(OH)D levels affects the parameters of muscle strength of the upper limbs for older adults living in a rural area and the muscle strength of the lower limbs for those living in an urban area.

Biochemical markers and anthropometric profile of children enrolled in public daycare centers.

OBJECTIVE: The nutritional status resultant from dietary habits along with socioeconomic conditions and the school environment are directly related to the individual's health condition not only in their childhood but also throughout adulthood. The aim of this study was to evaluate the effects of socioeconomic factors on the anthropometric profile and to analyze a probable association between this profile and biochemical markers in children attending public daycare centers. METHODS: It is a transversal study developed in a probability sample of clusters of children from 6 months to 5 years old. Anthropometric and socioeconomic data were gathered at the CMEIs, questionnaires on the nutritional status were applied and blood was collected at the Family Health Units (USFs). RESULTS: Female children are three times more likely to be underweight; in families with five members, it is 1/3 more likely that children of higher-educated parents are overweight. Among the results of the biochemical tests, hypervitaminosis A was a relevant aspect, positively correlating with copper (p=0.005) and zinc (p=0.008). CONCLUSION: Therefore, since the influence of the family is an important predictor of overweight and its future outcomes related to nutritional deficiencies and inadequate dietary intake, educational interventions are vital as a way to pave the path to prevention.

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.

Diagnostic potential of hypoxia-induced genes in liquid biopsies of breast cancer patients.

In tumor cells, higher expression of glucose transporter proteins (GLUT) and carbonic anhydrases (CAIX) genes is influenced by hypoxia-induced factors (HIF).Thus, we aimed to study the expression profile of these markers in sequential peripheral blood collections performed in breast cancer patients in order to verify their predictive potential in liquid biopsies. Gene expressions were analyzed by qPCR in tumor and blood samples from 125 patients and 25 healthy women. Differential expression was determined by the 2(-ΔCq) method. Expression of HIF-1α and GLUT1 in the blood of breast cancer patients is significantly higher (90-91 and 160-161 fold increased expression, respectively; p < 0.0001) than that found in healthy women. Their diagnostic power was confirmed by ROC curve. CAIX is also more expressed in breast cancer women blood, but its expression was detected only in a few samples. But none of these genes could be considered predictive markers. Therefore, evaluation of the expression of HIF-1α and GLUT1 in blood may be a useful laboratory tool to complement the diagnosis of breast cancer, in addition to being useful for follow-up of patients and of women with a family history of breast cancer.

Effects of Intravitreal Bevacizumab Therapy in Patients with Proliferative Diabetic Retinopathy.

INTRODUCTION: Diabetes mellitus (DM) stands out as one of the chronic diseases with the highest morbidity and mortality rates worldwide. Among the many complications of DM, diabetic retinopathy (DR) is one of the causes of blindness in patients aged between 20 and 64 years. At least 90% of the new cases showed to have the retinal structure and function restored when proper treatment was provided. AIM: To evaluate the efficacy of the antiangiogenic bevacizumab in the treatment of DR according not only to the clinical laboratory parameters for glycated hemoglobin (HbA1C) and capillary glycemia but also to the ophthalmological parameters for optical coherence tomography (OCT) and best-corrected visual acuity (BCVA). PATIENTS AND METHODS: A total of 11 individuals were included and followed up for 12 months after 3 administrations of bevacizumab. RESULTS: Upon associating the ophthalmological and laboratory variables throughout the treatment, no significant alterations could be seen regarding the analyzed variables. However, it was observed that HbA1c values and the total leukocyte count negatively interfered with the treatment response. CONCLUSION: The current study showed that HbA1c values and the amount of leukocytes negatively interfere with the therapeutic response. Therefore, laboratory analyses of these parameters are recommended for diabetic patients undergoing the above-mentioned treatment.

Liquid biopsy in cancer using the Z-scan technique: a new approach to discover biomarkers in cancer.

AIM: Biomarkers have been broadly studied as a tool for the diagnosis and prognosis for different types of cancer. Z-scan is a kind of measurement technique that generates a nonlinear refractive index (n2). Today, Z-scan has been used in oncology to discriminate between solid tumors and to identify tumor circulating cell-free DNA in liquid samples. MATERIALS & METHODS: According to the inclusion and exclusion criteria defined in this review, 35 articles were selected. CONCLUSION: The use of this technique for this kind of measurement will allow for a rapid and precise diagnosis of different types of tumor and may lead to better therapeutic approaches.

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.

Physical exercise alters hepatic morphology of low-density lipoprotein receptor knockout ovariectomized mice.

To explore the effects of physical exercise on the liver of animals in menopause, we analyzed the histomorphometric parameters of the hepatic tissue in ovariectomized and dyslipidemic female mice. The animals were distributed in six groups (n = 5): sedentary control (SC), sedentary ovariectomized control (SOC), trained ovariectomized control (TOC), sedentary LDL knockout (LDL-S), sedentary ovariectomized LDL knockout (LDL-SO), and trained ovariectomized LDL knockout (LDL-TO). At the end of the experiment, the liver and the visceral adipose tissue (VAT) of animals were removed for morphometric and stereological studies. In the LDL-S and LDL-SO animals, both sedentary, results showed reduction in the area (µm2) and major and minor diameters (µm) of hepatocytes and reduction in the portions of large hepatocytes, and increase in the percentage of Kupffer cells. The trained group showed a tendency of increase in the area and diameter and in the percentage of hepatocytes, as well significant reduction in the percentage of Kupffer cells and interstitial tissue. We suggested that training can prevent cell and tissue damage caused by the process of increase in hepatic fat, lipoperoxidation, and tissue inflammation in animals with privation of estrogen and dyslipidemia, apparently reflecting a better metabolic response of the hepatic tissue in organisms undergoing training.

Evaluation of breastfeeding self-efficacy of puerperal women in shared rooming units.

PURPOSE: To evaluate the perception of breastfeeding self-efficacy in puerperal women and to verify the association between Breastfeeding Self-Efficacy Scale-Brazilian Version (BSES-VB) scores and sociodemographic and obstetric variables. The practice of breastfeeding is of extreme importance, not only because of its affective value but also because the nutritional composition of human milk is essential nutrients for the adequate growth and development of the newborn. DESIGN AND METHODS: This is a quantitative and cross-sectional study. The sample consisted of 100 puerperal women. The research instruments used were form with demographic, economic, obstetric and breastfeeding data and the BSES-VB. RESULTS: 40% of the mothers obtained scores compatible with average breastfeeding self-efficacy, 35% of them presented high efficacy and 25% low efficacy. There was no significant relationship between sociodemographic and obstetric variables with the BSES-VB mean scores in the puerperal period. In the association between some variables and items of the breastfeeding self-efficacy scale, it was observed that breastfeeding guidance in the prenatal period and marital status were statistically significant with the mean scores of each item on the scale. CONCLUSION: Only 35% of the puerperal women presented high breastfeeding efficacy. Breastfeeding guidance variables in prenatal care and marital status were statistically significant. PRACTICE IMPLICATIONS: the work of the professionals who work in the care of puerperal women becomes of great importance to provide information on the breastfeeding theme and determining the adherence to the practice of breastfeeding.

Digitoxin improves cardiovascular autonomic control in rats with heart failure.

The effects of chronic treatment with digitoxin on arterial baroreceptor sensitivity for heart rate (HR) and renal sympathetic nerve activity (rSNA) control, cardiopulmonary reflex, and autonomic HR control in an animal model of heart failure (HF) were evaluated. Wistar rats were treated with digitoxin, which was administered in their daily feed (1 mg/kg per day) for 60 days. The following 3 experimental groups were evaluated: sham, HF, and HF treated with digitoxin (HF + DIG). We observed an increase in rSNA in the HF group (190 ± 29 pps, n = 5) compared with the sham group (98 ± 14 pps, n = 5). Digitoxin treatment prevented an increase in rSNA (98 ± 14 pps, n = 7). Therefore, arterial baroreceptor sensitivity was decreased in the HF group (-1.24 ± 0.07 bpm/mm Hg, n = 8) compared with the sham group (-2.27 ± 0.23 bpm/mm Hg, n = 6). Digitoxin did not alter arterial baroreceptor sensitivity in the HF + DIG group. Finally, the HF group showed an increased low frequency band (LFb: 23 ± 5 ms(2), n = 8) and a decreased high frequency band (HFb: 77 ± 5 ms(2), n = 8) compared with the sham group (LFb: 14 ± 3 ms(2); HFb: 86 ± 3 ms(2), n = 9); the HF+DIG group exhibited normalized parameters (LFb: 15 ± 3 ms(2); HFb: 85 ± 3 ms(2), n = 9). In conclusion, the benefits of decreasing rSNA are not directly related to improvements in peripheral cardiovascular reflexes; such occurrences are due in part to changes in the central nuclei of the brain responsible for autonomic cardiovascular control.