Aim of the study In cancer cells, NUR77/NR4A1 orphan receptors appear at the core of the functional picture as an oncogenic survival factor, however, it becomes a potent killer when certain ...activations of cell death phenomena occur. Material and methods The experimental studies we performed included the assessment of pro-B lymphocytes programmed death, induced as a result of activation of the NR4A1 orphan receptor, when treated with cytosporone A and gingival fibroblast-derived exosomes in the presence of apostatin 1, R-7050, and urolithin B. Results The real and distinguishable most important effects on apoptosis of pro-B lymphocytes, induced by cytosporone A, when also using exosomes liberated from gingival fibroblasts, were associated with the following reagents treatment: urolithin B, and R-7050. On the other hand, apostatin 1 had no significant effects when associated with cytospone A treatment. Conclusions So, inhibition of NF-κB pathway and of TNF-α receptors might increase the apoptotic degree induced by activation of NUR77/NR4A1 orphan receptors by cytosporone A, as well as the presence of exosomes derived from gingival fibroblasts. Moreover, the TRADD inhibition had no effects in the above conditions. The tumoral niche seems to be really of great importance when referring to the gingival tissue and leukemia precursors development.
Aim of the study The accelerated development of the tumor mass in acute lymphoblastic leukemia depends not only on the proliferative rate of cells but also on the rate of apoptosis, with NR4A1 dually ...controlling both the survival and death of tumoral cells. Material and methods The experimental plan of the actual studies was represented by highlighting the effects of the activation of the NR4A1 orphan receptor, in the presence of exosomes released from gingival fibroblasts, on the apoptosis of tumor precursors of B lymphocytes, pro-B respectively, and also in the presence of toll-like receptors, CXCL12, and necrosome modulators. Results The obtained results demonstrate that between the apoptosis induced by cytosporone B in the case of exosomes+ pro-B cells, after 48 hours of diverse treatments, and the control cells, there are statistically significant differences (the averages being comparatively 71.84% for 1 µM lipopolysaccharide; 91.25% for 1 µM AMG9810; 63.14% for 1 µM necrostatin 2 racemate; 61.77% for 1 µM tannic acid; and, respectively, 10% for control ones). Conclusions The most important effects of enhancing apoptosis induced by cytosporone B in the presence of exosomes released from gingival fibroblasts were under the following treatments: lipopolysaccharide in chronic conditions; inhibition of the functioning of TLR4 receptors; reduction of RNA for the toll-like receptors TLR4 and TLR2; and inhibition of the CXCL12 pathway. Thus, it is demonstrated that the exosomes of the tumoral microenvironment (gingival fibroblasts in this case) greatly influence the development of tumoral cells, in balance with apoptosis.
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.
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.
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.
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.
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%,
< 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 (
= 0.000), and troponin data were more nuanced relative to an overall, strongly significant decrease of 44,458 ng/L (
= 0.000). Troponin levels in patients with CKD dropped more, both in the presence of T2DM (by 82,500 ng/L,
= 0.000) and in patients without T2DM (by 73,294 ng/L,
= 0.047). As expected, the overall glycated hemoglobin (HbA1c) levels improved significantly in those with prediabetes (from 6.54% to 5.55%,
= 0.000); on the other hand, the mean HbA1c changed from 7.06% to 6.06% (
= 0.000) in T2DM, and the presence or absence of CKD did not seem to make any difference: T2DM+CKD 7.01-6.08% (
= 0.000), T2DM-CKD 7.08-6.04% (
= 0.000), PreD+CKD 5.66-4.98% (
= 0.014), and PreD-CKD 6.03-4.94% (
= 0.00). Compared to an overall gain of 11.51, the GFRs of patients with CKD improved by 18.93 (68.15-87.07%,
= 0.000) in the presence of established diabetes and 14.89 (64.75-79.64%,
= 0.000) in the prediabetes group.
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.
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.
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.
The subgroup of LBW patients accounted for 7.68% of all recorded cases. Girls were predominant (total M:
= 0.95; LBW group M:
= 0.91,
< 0.05), most from an urban area (total U:
= 1.29; LBW subgroup U:
= 1.36,
< 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
value of 0.0256,
= 0.7659 (
= 0.7659, 95% CI).
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.
Aim of the study We explored the relationships between the gingival fibroblasts and pro-B lymphocytes apoptosis in vitro because the current medical literature is lacking such data. Material and ...methods The aim of our study was represented by the effects of gingival fibroblasts on the apoptosis of Nur77 receptors-activated pro-lymphocytes in vitro, also in the presence of some retinoid derivatives. Gingival fibroblasts were obtained from male rats. Pro-B cells of murine type in cultures were used for actual experiments. The apoptosis of pro-B cells was induced using a combination of cytosporone B (50 µM) and cyclosporine A (1 µM). The apoptotic effects were revealed using the classical flow cytometry techniques. Results We clearly showed that pro-B lymphocyte apoptosis induced by the combination of cytosporone B (Nur77 agonist) and cyclosporine A in the presence of gingival fibroblasts could be slightly reduced by 13-cis retinoic acid. The inhibitory effects of 13-cis retinoic acid were powerful than those of tazarotenic acid. The effects of 13-cis retinoic acid and tazarotenic acid were evaluated toward the effects of the combination of cytosporone B and cyclosporine A. Conclusions The intrinsic pathways of retinoid derivatives remain to be established by further experiments
Of all the neoplastic sites, colorectal cancer (CRC) is one of the most common cancers in the family. Studies estimate that approximately 30% of all the CRC cases are a hereditary form of the disease ...with a potentially high impact on the quality of life (QoL), with a high risk of recurrence, and with bio–psycho–social functioning. The aim of the study was to assess the QoL of colorectal cancer patients with genetic risk by using the European Organisation for Research and Treatment of Cancer (EORTC) questionnaire version QLQ-CR29. Materials and methods: The cross-sectional, single-center study was performed on a group of 32 patients with genetic risk of colorectal cancer, who underwent preoperative chemoradiation and surgery. Results: The series of values for the scores on the symptom scale varied between 15 and 30, and the average level of symptom scores did not differ significantly between gender (22.0 vs. 22.75; p = 0.636), highlighting a moderate impairment of QoL. Scores for the emotional functioning scale were significantly lower in men (10.33 vs. 13.25; p = 0.049), as were the scores for the physical functions (15.67 vs. 19.15; p = 0.039), showing a decrease in QoL. Conclusions: The overall score showed an average QoL in patients with colorectal cancer with genetic risk, highlighting significant differences in psycho-emotional functioning between women and men.
Our studies aimed the effects of some endoplasmic reticulum stress inducers (thapsigargin, a Ca2+-ATP-ase inhibitor; tunicamycin, a protein N-glycosylation inhibitor; brefeldin A, a protein transport ...inhibitor; paraquat, an enhancer of reactive oxygen species production; A23187, a Ca2+ ionophore), as well as some antioxidants (N-acetylcysteine; dithiothreitol, a disulfide bond formation inhibitor) on apoptosis of cultured rat mesenchymal stem cells. The analyze of obtained results evidenced that paraquat, a common and effective herbicide, induced the apoptosis of the isolated rat mesenchymal stem cells in a larger proportion as compared to other chemicals as follows: paraquat thapsigargin tunicamycin @A23187 brefeldin A. Dithiothreitol was effective as a reducer of mesenchymal stem cells apoptosis when was administered as co-treatment for paraquat for 24 h. In contrast, N-acetylcysteine, another potent antioxidant, had no protective effects against paraquat apoptotic effects.
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.
The present studies aimed the effects of tyrphostin AG 494 and tyrphostin AG 1295 on apoptosis of mouse pro-B lymphocytes. The actual scientific literature lacks such data. Tyrphostin AG 494 is an ...inhibitor of epidermal growth factor receptor pathways and tyrphostin AG 1295 is an inhibitor of platelet-derived growth factor receptor pathways. Our obtained data demonstrated that tyrphostin AG 1295 was less effective in preventing the apoptosis of murine pro-B cells, triggered by the combination of Cytoporone B (NR4A1 agonist) and Cyclosporine A. In contrast, tyrphostin AG 494 had a stronger inhibitory effect on the apoptosis of the same cells, when administered for 24 hours. Thus, when blocking the activation of epidermal growth factor receptor pathways, the inductive apoptotic effects of Cytoporone B and Cyclosporine A are reduced. Thus, we could conclude that such inhibition will increase the resistance to apoptosis of pro-B cells. Thus, such a resistance to apoptosis could be experimentally acquired by hematopoietic cells.
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