Apoptosis of pro-B lymphocytes induced by NR4A1 activation in the presence of gingival fibroblast exosomes and TNFα, caspase 8, STAT3, and Akt pathways modulators.

There is a lack of data in the mainstream literature regarding the interactions between gingival fibroblasts, as a component of the local niche, and tumor precursors of B-lymphocytes. Although it is known that the development of tumors and tumor precursors depends on the local environment's characteristics. In order to experimentally evaluate the apoptosis of pro-B type lymphocytes, induced as a result of the known activation of orphan nuclear receptor 4A1 (NR4A1), through Cytosporone B (Csn-B, 10 µM), in the presence or absence of exosomes derived from gingival fibroblasts, we administered as a treatment: 1 µM R-7050 [functional inhibitor of tumor necrosis factor alpha (TNFα)], 1 µM Z-IETD-FMK (functional inhibitor of caspase 8), 1 µM GSK690693 (functional inhibitor of Akt 1∕2∕3 pathways) and, last but not least, 1 µM scutellarin [functional inhibitor of receptor activator of nuclear factor-kappa B ligand (RANKL)] and therefore of the signal transducer and activator of transcription 3 (STAT3) pathway. Firstly, it is really clear that the presence of exosomes in the pro-B lymphocytes culture medium amplified the apoptotic effects of 10 µM Csn-B. The inhibition of tumoral precursors development, namely the pro-B type, might be highly dependent on the inhibition of Akt 1∕2∕3 pathways, the first and most important consequence being apoptosis induced by the activation of NR4A1 orphan nuclear receptors.

Post-Coronary Artery Bypass Grafting Outcomes of Patients with/without Type-2 Diabetes Mellitus and Chronic Kidney Disease Treated with SGLT2 Inhibitor Dapagliflozin: A Single-Center Experience Analysis.

INTRODUCTION: Increasingly, SGLT2 inhibitors save patients with heart failure and comorbidities such as type-2 diabetes mellitus (T2DM) and chronic kidney disease (CKD); the inhibition of sodium-glucose cotransporter 2 (SGLT2) was first studied in patients with diabetes as a solution to lower glucose levels by preventing glucose reabsorption and facilitating its elimination; in the process, researchers took notice of how SGLT2 inhibitors also seemed to have beneficial cardiovascular effects in patients with both diabetes and cardiovascular disease. AIM: Our single-center prospective study assesses outcomes of post-coronary artery bypass grafting (CABG) rehabilitation and SLGT2 inhibition in CABG patients with/without T2DM and with/without CKD. MATERIALS AND METHODS: One hundred twenty consecutive patients undergoing CABG were included in the analysis. Patients were divided into four subgroups: diabetes patients with chronic kidney disease (T2DM + CKD), diabetes patients without chronic kidney disease (T2DM-CKD), prediabetes patients with chronic kidney disease (PreD+CKD), and prediabetes patients without chronic kidney disease (PreD-CKD). Echocardiographic and laboratory investigations post-surgery (phase I) and 6 months later (phase II) included markers for cardiac ischemia, glycemic status, and renal function, and metabolic equivalents were investigated. RESULTS: One hundred twenty patients participated, mostly men, overweight/obese, hypertensive, smokers; 65 had T2DM (18 with CKD), and 55 were prediabetic (17 with CKD). The mean ejection fraction increased by 8.43% overall but significantly more in the prediabetes group compared to the T2DM group (10.14% vs. 6.98%, p < 0.05). Overall, mean heart-type fatty-acid-binding protein (H-FABP) levels returned to normal levels, dropping from 68.40 ng/mL to 4.82 ng/mL (p = 0.000), and troponin data were more nuanced relative to an overall, strongly significant decrease of 44,458 ng/L (p = 0.000). Troponin levels in patients with CKD dropped more, both in the presence of T2DM (by 82,500 ng/L, p = 0.000) and in patients without T2DM (by 73,294 ng/L, p = 0.047). As expected, the overall glycated hemoglobin (HbA1c) levels improved significantly in those with prediabetes (from 6.54% to 5.55%, p = 0.000); on the other hand, the mean HbA1c changed from 7.06% to 6.06% (p = 0.000) in T2DM, and the presence or absence of CKD did not seem to make any difference: T2DM+CKD 7.01-6.08% (p = 0.000), T2DM-CKD 7.08-6.04% (p = 0.000), PreD+CKD 5.66-4.98% (p = 0.014), and PreD-CKD 6.03-4.94% (p = 0.00). Compared to an overall gain of 11.51, the GFRs of patients with CKD improved by 18.93 (68.15-87.07%, p = 0.000) in the presence of established diabetes and 14.89 (64.75-79.64%, p = 0.000) in the prediabetes group. CONCLUSIONS: Regarding the patients' cardiac statuses, the results from our single-center analysis revealed a significant decrease in ischemic risk (H-FABP and hs-cTnI levels) with improvements in mean ejection fraction, glycemic status, and renal function in patients post-CABG with/without T2DM, with/without CKD, and with SGLT2 inhibitor dapagliflozin treatment while undergoing cardiac rehabilitation.

Association between Cone-Beam Computed Tomography and Histological and Immunohistochemical Features in Periapical Lesions Correlated with Thickened Maxillary Sinus Mucosa.

Background and Objectives: Odontogenic sinusitis is a frequently underestimated pathology with fewer symptoms in patients with periapical lesions, periodontal disease, or iatrogenic foreign bodies in the maxillary sinus. The aim of our study was to determine the correlation between maxillary sinusitis and periapical lesions using cone-beam computed tomography (CBCT) imaging and histological and immunohistochemical investigations. Materials and Methods: A total of 1450 initial patients diagnosed with maxillary sinusitis in the Ear-Nose-Throat (ENT) Department, University of Medicine and Pharmacy "Grigore T. Popa" Iasi, Romania, were treated with anti-inflammatory drugs. Of these, 629 still had unresolved symptomatology and were later referred to the Dental Medicine departments for further investigations. Only 50 subjects with periapical lesions in the premolar/molar maxillary area were included in the present study. All the periapical lesions were observed on CBCT and classified using the Periapical Status Index (PSI) and the mean maxillary sinus mucosa thicknesses (MSMT). The enrolled patients underwent surgical procedures with the excision of periapical lesions. The excised samples were submitted to the histological and immunohistochemical investigations. Results: The 50 patients presented periapical lesions of their maxillary teeth in 328 dental units. There was a higher prevalence of periapical lesions in men than in women (chi-square test). We observed a significant difference between the mean MSMT of individuals with periapical lesions compared to those without (p < 0.01). Mean MSMT was 1.23 mm for teeth without periapical lesions and 3.95 mm for teeth with periapical lesions. The histopathological study identified 50% cases with periapical granulomas, 10% cases with periapical granulomas with cystic potential, and 40% cases as periapical cysts. Immunohistochemical stainings showed that CD4+ helper and CD8+ cytotoxic T lymphocytes, along with CD20+ B lymphocytes and CD68+ macrophages, were diffusely distributed in all periapical cysts and in some periapical granulomas, but CD79α+ plasma cells characterized especially periapical granulomas. Conclusions: The current study observed a significant correlation between CBCT maxillary mucosa thickness and type of periapical lesion. Chronic inflammatory lympho-histiocytic infiltrate predominates in periapical lesions, supporting the idea that lesion progression is determined by a humoral-type (CD20+ and CD79α+ B lymphocytes) but also by a cellular-type (CD4+ and CD8+ T lymphocyte population) immune mechanism.

Risk of tuberculosis in low birth weight children from East Romania.

INTRODUCTION: In the context of the global tuberculosis (TB) burden, children represent 10% of all cases, with high incidence rates still reported by many regions worldwide. The study aim was to determine whether there is a correlation between TB clinical diagnosis and low birth weight in children at various ages. MATERIAL AND METHODS: The study was conducted between 2010 and 2014, on a group of 1783 pediatric patients and a subgroup of 137 pediatric patients with low birth weight (LBW). Data were collected from patients' records and hospital statistical reports then processed using MS Excel 2010 and SPSS v.22. RESULTS: The subgroup of LBW patients accounted for 7.68% of all recorded cases. Girls were predominant (total M: F = 0.95; LBW group M: F = 0.91, p < 0.05), most from an urban area (total U: R = 1.29; LBW subgroup U: R = 1.36, p < 0.05). 22.59% of LBW subgroup children were infants aged of 0-12 months. The youngest age at TB diagnosis was 1 month and the lowest weight was 700 g. ANOVA regression for LBW and age at TB diagnosis, showed a multiple R value of 0.0256, p = 0.7659 (F = 0.7659, 95% CI). CONCLUSIONS: The correlation between clinical diagnosis of tuberculosis in children at various ages and their low birth weight was positive but was not statistically significant. However, this research hypothesis should be tested in further studies on larger population groups, due to the current public health context of "End TB", promoted worldwide.

Polycystic Ovary Syndrome, A Complex Entity Involving Reproductive and Metabolic Impairments: A Systematic Review.

We attempt to synthesize main data in what concerns pathogenesis, signs and symptoms, diagnosis and management of polycystic ovary syndrome PCOS. The issue was the systematization of main data regarding different features of PCOS and stressing its peculiar association with characteristics of metabolic syndrome, main diagnostic criteria and most important therapeutic options, finally contouring an updated general picture of PCOS. We pointed also on associated morbidities, such as endometrial cancer, insulin resistance and need for individualized therapy, including changing in lifestyle, especially weight loss.

Genetic polymorphisms of TNFA and IL-1A and generalized aggressive periodontitis.

Virulent bacteria could cause gingival fibroblasts apoptosis through lipopolysaccharide release during generalized aggressive periodontitis (GAgP) development and evolution. We showed that treatment with lipopolysaccharide (LPS, 1 µg/mL) for 30 days induced the decrease in the number of cultured rat gingival fibroblasts as compared to control group, which received no treatment. GAgP is considered to have also a genetic etiology, so the aim of our study was to evaluate if some polymorphisms of tumor necrosis factor-alpha (TNFA) and interleukin 1A (IL-1A) genes are associated with GAgP in a sample of Romanian population. We selected a group of 32 subjects (22 cases and 10 controls) for studying the TNFA (-857) polymorphism and 97 subjects (66 cases and 31 controls) for IL-1A (-889) polymorphism. The single nucleotide polymorphisms were genotyped by real-time polymerase chain reaction for all subjects. The genotype and allelic distribution tended to be equally between the cases and the controls group. Similar results were obtained for the dominant and recessive model. The difference between the two groups did not reach statistic significance for neither of the two studied polymorphisms [p=0.76 for TNFA (-857) and p=0.84 for IL-1A (-889)]. The data suggest that TNFA (-857) C/T and IL-1A (-889) C/T polymorphisms are not associated with susceptibility to GAgP in this Romanian population, potentially because of the small sample size. This is the first such study for Romanian northeastern population.

ETHICAL AND DEMOGRAPHICAL ISSUES IN SCREENING FOR CERVICAL CANCER--AN OUTLINE IN NORTH EASTERN REGION OF ROMANIA.

AIM: This study complements the national screening program for cervical cancer, implemented in Romania. MATERIAL AND METHODS: Inclusion criteria for this program of active detection of cervical cancer are women aged 25 to 64 years and exclusion criteria were other age groups and the diagnosis confirmed of cervical cancer. The testing was free and used the method of colored cervical smear Pap. RESULTS: In 2013, 23.680 women were tested, that means only 10.13% of the total female population eligible for screening. In 2014, the test group was 6337 (one smear required retesting), of which 5852 were negative results and 484 positive results. Squamous cell abnormalities were detected in 433 women (6.84% of total group who attended the screening). Cervical smears with atypical squamous lesions were present at the most women included in the screening, regardless of age group (67.43%). The screening detected 21 lesions HSIL (4.84%), 2 HSIL with suspicion of invasion (0.46%) and 5 lesions of squamous carcinoma (1.15%). CONCLUSIONS: The presence of a small number of people compared to the female population eligible to the test screening may show the need for a better spread of notions about the screening and the afferent national program, for the population in northeastern Romania, considering the ethical issues that this test assumes.

Nutritional factors in transdifferentiation of scheletal muscles to adipocytes.

A current area of interest is the determination of factors able to promote the transition from muscle to adipose tissue. The current review has highlighted that treatment of myoblasts with fatty acids (especially oleic acid) and thiazolidindiones causes conversion to adipocytes. The molecular mechanisms mediating the adipogenic action of thiazolidinediones and fatty acids in myoblasts could involve peroxisome proliferators-activated receptor-gamma (PPARgamma and CCAAT-enhancer-binding protein C/EBP. The role of 1,25-D3 in adipogenesis is mediated at the molecular level through VDR-dependent inhibition of C/EBP and PPARgamma expression and a decrease in PPARgamma transactivation activity. Vitamin D supplementation increases muscle strength and ultimately reduces the incidence of falls. Additional research is needed to fully clarify the role of nutritional factors in adipogenesis.

Metabolic syndrome a widespread threatening condition; risk factors, diagnostic criteria, therapeutic options, prevention and controversies: an overview.

Metabolic syndrome diagnostic criteria include at least three of five of the following medical conditions: abdominal obesity, high blood pressure, abnormal high fasting plasma glucose, elevated serum triglycerides and low HDL (high-density cholesterol) level. Sedentary, overweight and obesity are characteristically associated with the syndrome, nevertheless there are new studies which indicate that chronic stress, through deregulation of the hypothalamic-pituitary-adrenal (HPA) axis is also involved in the development of the syndrome. Metabolic syndrome represents a significant risk for the development of the cardiovascular diseases. New studies in the USA have estimated its prevalence at approximately 34% of the adult population and its prevalence is increasing with age. Diagnosis guidelines are establishing the metabolic syndrome diagnostic when are met three of the following five conditions: fasting glucose > or = 100 mg/dL or type 2 diabetes receiving drug therapy for hyperglycemia; high blood pressure > or = 130/85 mm Hg or high blood pressure receiving drug therapy; triglycerides > or =150 mg/dL or treatment for plasma hyper-triglyceride value; HDL-C < 40 mg/dL in men and < 50 mg/dL in women or if under therapy for reduced HDL-C levels and waist circumference of > or = 102 cm in men and > or = 88 cm in women. Besides important change of lifestyle, often drug therapy is needed (diuretics and ACE inhibitors, cholesterol drugs and weight loss medications). The value of physical activity and diet in prevention and treatment of the syndrome is supported by numerous studies. Association of metabolic syndrome and cardiovascular risk is still a matter of controversy, in what concerns the lack of significant cardiovascular risk in the case of obesity itself without metabolic syndrome.

Apelin effects on lipopolysaccharide-increased pulmonary permeability in rats.

MATERIAL AND METHOD: Pretreatment with apelin-13 (AP-13, 2 mg/kg, i.p.), sodium butyrate (BUT, 200 mg/kg, s.c.) and N-acetyl-L-cysteine (NAC, 150 mg/kg, s.c.), all reduced the LPS-induced vascular leak measured as Evans blue extravasation, in rats lung tissue when compared to intranasal LPS (10 mg/100 mL) administered alone. RESULTS: Although there is a significant difference either between AP-13 and BUT on one hand, and NAC and BUT on the other hand pretreatments, there is no significant difference between AP-13 and NAC pretreatments. Firstly, apelin-13 pretreatment might justify its effects through the modulation of endothelial layer functions. We recently demonstrated that AP-13 could diminish the endothelial dysfunction of pulmonary vein from both ovalbumin sensitized rats and rats with pulmonary hypertension. Furthermore, pretreatment with AP-13 + BUT, AP-13+NAC as well as BUT+ NAC reduced the LPS-induced vascular leak when compared to LPS alone. The reduction effects of BUT and NAC association were higher than those of either BUT or NAC alone. These synergistic effects might be associated to different and additive mechanisms of action of BUT and NAC. Thus, BUT might be primarily effective on macrophage migration and secondarily on activation and cytokine secretion by macrophages and NAC might be primarily effective on macrophages activation. Furthermore, since there are no significant effects between AP-13, NAC and AP-13+NAC we can conclude that AP-13 and NAC effects might be mediated through the same mechanisms (with the possible involvement of nuclear transcription factor NF-kB).