Serum Bcl-2 Research Articles

Serum L C3-II levels in type 2 diabetic patients with impaired renal functions

This study was designed to evaluate serum LC3-II, BCL-2, IL-1β, TGF-β1, and podocin levels in.type 2 diabetes (T2DM) patients with renal dysfunction. Materials176 Turkish subjects were enrolled, of whom 26 were healthy, and 150 had T2DM. Patients.were classified according to albumin urea ratio: 88 patients had macroalbuminuria, 20.patients had microalbuminuria, and 42 had normoalbuminuria. T2DM patients were also.classified into three groups according to proteinuria and eGFR stages. ResultsIncreased serum LC3-II levels in patients with T2DM with increased urinary albumin.extraction and impaired renal functions. There was a strong relationship between serum.LC3-II levels and serum BCL-2, IL-1β, TGF-β1, and Podocin levels. The efficiency of LC3-II as a diagnostic biomarker in the differential diagnosis of DM patients with.macroproteinuria from DM patients with normoproteinuria was 75.4%. ConclusionsIt was thought that increased serum LC3-II levels in T2DM patients with impaired renal.functions may cause renal podocyte damage. In these patients, serum LC3-II levels can be.evaluated as a new biomarker to follow the development of renal damage.

Serum GAS6, sAXL, IL-10, NO, and BCL-2 levels are decreased in patients with Behçet's disease.

Behçet's disease (BD) is an autoimmune chronic systemic inflammatory disease characterized by a versatile clinical spectrum. Growth arrest specific protein 6 (GAS6)/soluble AXL (sAXL) signaling pathway draws attention in the resolution of inflammation, and its deficiency is associated with chronic inflammatory, autoimmune diseases, as well as clearance of apoptotic cells by phagocytes - efferocytosis. In this study, it was aimed to investigate whether GAS6/sAXL, interleukin (IL)-10, nitric oxide (NO), and BCL-2 levels were associated with inflammation and efferocytosis contributes to the pathogenesis of BD. A total of 37 Behçet patients with ocular involvement and 30 healthy control subjects were included in this study. GAS6, sAXL, IL-10, NO, and BCL-2 levels were quantified using enzyme-linked immunosorbent assay (ELISA) method. Serum GAS6, sAXL, IL-10, NO, and BCL-2 levels were significantly lower in patients with BD compared to the controls (P < 0.005, P < 0.001, P < 0.001, P < 0.001, and P < 0.001, respectively). In correlation analysis, research parameters decreased in patients with BD was significantly correlated with each other: GAS6-IL-10 (r = 0.585, P < 0.001), GAS6-BCL-2 (r = 0.541, P < 0.001), sAXL-BCL-2 (r = 0.696, P < 0.001), IL-10-NO (r = 0.717, P < 0.001), IL-10-BCL-2 (r = 0.759, P < 0.001), and NO-BCL-2 (r = 0.541, P < 0.001). In conclusion, decreased serum BCL-2 level may be an indicator of increased apoptosis in these patients and decreased levels of GAS6/sAXL, IL-10, and NO may indicate insufficient clearance of apoptotic bodies released as a result of increased apoptosis in BD patients.

Erythropoietin alleviates lung ischemia-reperfusion injury by activating the FGF23/FGFR4/ERK signaling pathway.

The purpose of the present study was to investigate the effect of erythropoietin (EPO) on lung ischemia-reperfusion injury (LIRI). Sprague Dawley rats and BEAS-2B cells were employed to construct an ischemia-reperfusion (I/R)-induced model in vivo and in vitro, respectively. Afterward, I/R rats and tert-butyl hydroperoxide (TBHP)-induced cells were treated with different concentrations of EPO. Furthermore, 40 patients with LIRI and healthy controls were enrolled in the study. It was observed that lung tissue damage, cell apoptosis and the expression of BAX and caspase-3 were higher in the LIRI model in vivo and in vitro than in the control group, nevertheless, the Bcl-2, FGF23 and FGFR4 expression level was lower than in the control group. EPO administration significantly reduced lung tissue damage and cell apoptosis while also up-regulating the expression of FGF23 and FGFR4. Rescue experiments indicated that EPO exerted a protective role associated with the FGF23/FGFR4/p-ERK1/2 signal pathway. Notably, the expression of serum EPO, FGF23, FGFR4 and Bcl-2 was decreased in patients with LIRI, while the expression of caspase-3 and BAX was higher. EPO could effectively improve LIRI, which might be related to the activation of the FGF23/FGFR4/p-ERK1/2 signaling pathway.

Increased cancer risk in HIV-infected individuals occupationally exposed to chemicals: Depression of p53 as the key driver.

The growing exposure to occupational chemicals and the spread of human immunodeficiency virus (HIV) infection are major global health issues. However, there is little data on the carcinogenic risk profile of HIV-infected individuals who have been occupationally exposed to chemical mixtures. This study therefore investigated the levels of cancer risk biomarkers in HIV-infected individuals exposed to occupational chemicals, exploring the relationship between apoptotic regulatory and oxidative response markers as a measure of cancer risk. Study participants (mean age 38.35±0.72 years) were divided into four groups according to their HIV status and occupational chemical exposure: 62 HIV-positive exposed (HPE), 66 HIV-positive unexposed (HPU), 60 HIV-negative exposed (HNE), and 60 HIV-negative unexposed (HNU). Serum p53, β-cell lymphoma-2 (bcl2), 8-hydroxydeoxyguanosine (8-OHdG), superoxide dismutase (SOD), and malondialdehyde (MDA) were measured using standard methods. Clusters of differentiation 4 (CD4+) T-lymphocytes were enumerated using flow cytometry. Serum p53 and bcl2 levels in HPE (0.91±0.11ng/ml and 122.37±15.77ng/ml) were significantly lower than HNU (1.49±0.15ng/ml and 225.52±33.67ng/ml) (p < 0.05), respectively. Wildtype p53 and bcl2 were positively and significantly correlated with 8-OHdG (r = 0.35, p<0.001; r = 0.36, p<0.001) and SOD (r = 0.38, p<0.001; r = 0.39, p<0.001). After controlling for gender, age, BMI, and cigarette smoking, both HIV status and SOD activity were significantly associated with wildtype p53 and bcl2 (p < 0.05). Malondialdehyde was significantly higher in the HPE (0.72 ± 0.01 mg/ml) than in the HNE (0.68 ± 0.01 mg/ml) and HNU (0.67 ± 0.01 mg/ml) groups (p < 0.05). The HPE group showed significantly lower CD4 counts than the HNE and HNU groups. Individuals who are HIV-infected and occupationally exposed to chemicals have a constellation of depressed immunity, elevated oxidative stress, and loss of tumour suppressive functions, which together intensify cancer risk, providing valuable scientific and public health bases for preventive measures in this vulnerable population.

Preventive effect and mechanism of compound Danshen dripping pills on contrast-induced nephropathy after percutaneous coronary interventional.

Contrast-induced nephropathy (CIN) is one of the most common complications after coronary stent implantation due to the extensive development of coronary catheterization technology. Compound Danshen dripping pills (CDDP) are clinically used as cardiovascular drugs, relieving systemic inflammatory response. Previous studies have observed that CDDP can decrease CIN incidence after coronary stent implantation with uncertain effectiveness. We conducted a prospective, randomized, single-center, single-blind, controlled trial. We enrolled patients 18 years and older with unstable angina pectoris and NSTEMI who underwent PCI at the Tianjin Chest Hospital between November 1, 2021, and November 31, 2022, and followed for 30 days. Patients were randomized to CDDP and hydration therapy (10 capsules three times/day; N = 411) or hydration only (N = 411). The primary outcome was the contrast nephropathy incidence, defined as an elevation in serum creatinine by more than 25% or 44 μmol/L from baseline within 48-72 h of contrast exposure. Secondary outcomes included major adverse cardiovascular events post-surgery and during follow-up. After 48 h of operation, the two groups had statistical significance in Scr and BUN values (80.0 ± 12.59 vs. 84.43 ± 13.49, P < 0.05; 6.22 ± 1.01 vs. 6.40 ± 0.93, P < 0.05). The difference in Scr in 72 h between the two groups was statistically significant (76.42 ± 10.92 vs. 79.06 ± 11.58, P < 0.05). The CIN incidence was significantly lower in the CDDP group than in the hydration group. The CIN risk was significantly elevated in patients with LVEF <50%, contrast volume ≥160 ml, and hypertension, after 48 and 72 h of operation. The serum inflammation index levels NGAL, TNF-α, oxidative stress indexes SOD, and MDA significantly differed between the two groups. However, there was no significant difference in serum apoptosis indexes Bax, Bcl-2, and Casepase-9. CDDP pre-treatment could prevent contrast-induced nephropathy. Inflammatory response and oxidative stress could be significant in the CDDP mechanism.

Evaluation of the combined effects of Turkish mad honey and 5-Fluorouracil in colon cancer model in rats

It was aimed to evaluate the regressive effect of grayanotoxin-rich Turkish mad honey and 5-fluorouracil (5-FU), separately and together by using the N-methyl-N-nitrosourea (MNU)-induced colon cancer modelling in rats. Study groups were designed as control group (CG), cancer control group (CCG), 5-Flourouracil group (FUG), Turkish mad honey group (HG), Turkish mad honey and 5-FU combined group (FU-HG). White blood cell (WBC), lymphocyte, eosinophil, basophil, serum lactate dehydrogenase (LDH), total oxidant status (TOS), and total protein values of the rats in the CCG were significantly lower than the values of the rats in the CG, whereas serum Bcl-2 and survivin levels were significantly higher in the rates belonged to the CCG in comparison to those in the CG. The presence of anaplastic epithelial cells, vascularization, precancerous changes, and inflammatory infiltration detected in the colon and small intestine of the rats in FU-HG, FUG, HG were less intense (P&amp;lt;0.05) compared to the findings in the rats in CCG. In conclusion, mad honey and 5-FU reduced anaplastic cell growth and oxidative stress via suppressed anti-apoptotic activity. Considering the histopathological findings in the liver and kidney, no toxicity occurred related to mad honey and 5-FU metabolization. Therefore, the combined use of these two substances may be an alternative method in the treatment of colon cancer.

CHANGES ANALYSIS OF THE HEPATOCYTE APOPTOSIS MARKERS LEVELS IN MALIGNANT OBSTRUCTIVE JAUNDICE COMPLICATED BY CHOLANGITIS.

The aim: To evaluate changes in the levels of hepatocyte apoptosis markers in malignant obstructive jaundice (MOJ) depending on the performance of preoperative biliary decompression (PBD) and the severity degree of primary ascending cholangitis (PAC). Materials and methods: 136 patients with MOJ complicated by cholangitis were included in the study: group A (n=84) - patients who underwent PBD; group B (n=52) - patients without PBD. The level of CASP3 and Bcl-2 (Human Bcl-2(B-cell Leukemia/Lymphoma 2) in blood serum and bile was assessed according to the principle of Sandwich-ELISA. Material collection for research was performed at the PBD stage and intraoperatively. Results: Comparative analysis of CASP3 levels in patients of the study groups revealed that the level of this indicator in the blood and bile of group A patients was statistically significantly higher compared to group B, p=0,004 and p<0,001, respectively. There was no statistically significant difference between the study groups in the intraoperative levels of blood serum Bcl-2 (p=0,786) and bile Bcl-2 (p=0,439). The presence of a correlation between apoptosis markers in group A patients with I and II degree of PAC at the time of PBD and the main surgical intervention was determined: blood serum CASP3 - r=0,733, p<0,001 and r=0,753, p<0,001; bile CASP3 - r=0,716, p<0,001 and r=0,792, p<0,001; blood serum Bcl-2 - r=0,609, p<0,001 and r=0,495, p=0,002; bile Bcl-2- r=0,744, p<0,001 and r=0,497, p=0,002, respectively. Binary logistic regression analysis showed that the development of grade I and II PAC did not relate with the levels of apoptosis markers (p>0.05). Linear regression analysis revealed a correlation between the levels of Bcl-2 in bile during PBD and intraoperatively in group A patients with moderate grade OJ (R2=0,547, p<0,001) and between the levels of CASP3 in blood serum (R2=0,614, p<0,001), CASP3 in bile (R2=0,603, p<0,001), Bcl-2 in blood serum (R2=0,484, p<0,001) and Bcl-2 in bile (R2=0,485, p<0,001) in PBD and intraoperatively in patients with severe grade OJ. A statistically significant difference in the levels of Bcl-2 in blood serum (p<0,001) and Bcl-2 in bile (p=0,016) was found when comparing apoptosis markers in patients with moderate grade OJ of the study groups. Binary logistic analysis showed that the performance of PBD had a significant (reducing) effect on CASP3 levels in blood serum and bile taken intraoperatively in study groups patients with moderate grade OJ (R2= 0,292, p<0,001; R2= 0,184, p<0,001). Conclusions: Prolonged OJ leads to the pathological apoptosis process. The performance of PBD statistically significantly reduces the level of CASP3 in blood serum and bile, which is confirmed by further determination intraoper¬atively in patients with OJ complicated by PAC, p<0,001. Staged surgical intervention with the performance of PBD according to clear indications is a necessary treatment strategy in patients with MOJ complicated by cholangitis.

Circulating levels of Bcl-2 and its expression in the nasal mucosa of patients with chronic rhinosinusitis

&lt;b&gt;Aim: &lt;/b&gt;To evaluate expression of anti-apoptotic Bcl-2 protein in the nasal tissue and its levels in blood serum of patients with chronic rhinosinusitis with (CRSwNP) and without nasal polyps (CRSsNP).&lt;br /&gt; &lt;b&gt;Material and methods:&lt;/b&gt; Expression of Bcl-2 in the sinonasal tissue and its levels in blood serum of patients with CRSsNP and CRSwNP were evaluated immunohistochemically and using ELISA, respectively.&lt;br /&gt; &lt;b&gt;Results:&lt;/b&gt; In patients with CRSsNP, Bcl-2 was overexpressed in nasal epithelial cells mainly in the atrophic regions. However, its upregulation was also observed in regions with epithelial cell proliferation. Immunostaining for Bcl-2 was stronger both in the stroma and epithelial lining compared with control subjects. The level of Bcl-2 in blood serum was elevated in both forms of chronic rhinosinusitis with a more pronounced increase in CRSwNP.&lt;br /&gt; &lt;b&gt;Conclusion:&lt;/b&gt; CRSsNP and especially CRSwNP are associated with overexpression of anti-apoptotic Bcl-2 in nasal epithelial and cells in the lamina propria against the background of elevated circulating concentrations of Bcl-2.

Hormonal, apoptotic, proliferative and inflammatory markers' expression in Desogestrel-treated women with ovarian endometriosis.

Endometriosis is a relatively frequent pathology in gynecological practice. We performed an analysis to demonstrate the molecular changes that occur in endometriosis synthetic progestin-treated patients, hoping to sketch a possible pathophysiological pathway that will help us to better understand and treat this debilitating disease. We conducted a prospective study that included a group of 40 women, evaluated in our hospital between 2020-2021. We evaluated immunohistochemical tissue expression of estrogen receptor (ER), progesterone receptor (PR), B-cell lymphoma 2 (Bcl-2) protein, Ki-67, and serum levels of osteopontin (OPN) and vascular endothelial growth factor (VEGF) in patients with ovarian endometrioma with and without progestin treatment. Our study revealed that Desogestrel treatment increases OPN serum levels, PR and Bcl-2 tissue expression and reduces VEGF serum levels and Ki-67 tissue expression. The results we have obtained are very interesting because the serum levels of OPN seem to be more influenced by progestin treatment, than by endometriosis itself. The study we have conducted gives a molecular complex view of what endometriosis represents and on how Desogestrel treatment works.

Blood Bcl-2 levels to predict themortality of septic patients.

Aim: To determine whether blood concentrations of Bcl-2 during the 1st week of sepsis could help predict mortality. Methods: Serum Bcl-2 concentrations were determined at the 1st, 4th and 8th days of sepsis diagnosis. Results: Thirty-day surviving patients (n=168) showed higher serum Bcl-2 levels at the 1st (p=0.002), 4th (p<0.001) and 8th days (p<0.001) of sepsis diagnosis than non-surviving patients (n=91). An association between serum Bcl-2 concentrations at the 1st (p=0.003), 4th (p<0.001) and 8th days (p=0.01) and 30-day mortality after controlling for diabetes mellitus, Sepsis-related Organ Failure Assessment, lactic acid and age was found in the multiple logistic regression analysis. Conclusions: The novel finding is that blood Bcl-2 concentrations at any time in the 1st week of sepsis are associated with mortality.

Trifolium pratense extract increases testosterone and improves sperm characteristics and antioxidant status in diabetic rats

ABSTRACT Male reproductive dysfunction is a common complication of diabetes mellitus. Trifolium pratense exhibits antioxidant and antidiabetic effects. We investigated the effects of an extract of T. pratense on serum antioxidant status, sperm characteristics, testicular tissue changes and testosterone level in diabetic rats. Male Wistar rats were divided into six groups: 1, untreated control; 2, diabetic; 3 and 4, 100 or 200 mg/kg T. pratense extract treated, respectively; 5 and 6, diabetic 100 or 200 mg/kg T. pratense extract treated, respectively. Diabetes was induced by intraperitoneal injection of streptozotocin. After 3 weeks, serum glucose, testosterone and nitric oxide (NO); sperm parameters; testicular histology and total antioxidant capacity (TAC) were evaluated. In diabetic rats treated with T. pratense extract, sperm motility, count and viability, as well as TAC and testosterone were increased significantly compared to untreated diabetic rats, while serum NO and bcl-2 and p53 expression was decreased significantly compared to untreated diabetic rats. T. pratense extract reduced testicular tissue destruction caused by diabetes.

Association between serum concentrations of anti-apoptotic B-cell lymphoma-2 protein and traumatic brain injury mortality

ABSTRACT Background There are scarce and contradictory data existing about B-cell lymphoma 2 (Bcl2), one of the Bcl2 family of anti-apoptotic proteins, in traumatic brain injury (TBI) patients. Thus, the objective of this study was to analyze whether blood concentrations of Bcl2 are associated with mortality. Methods Patients with isolated and severe TBI, defined as <10 points of the Injury Severity Score (ISS) in non-cranial aspects and <9 points in Glasgow Coma Scale (GCS), were included. This was an observational and prospective study carried out in five Intensive Care Units. Serum Bcl2 concentrations on day 1 of TBI were determined. Results Serum Bcl2 concentrations were lower (p < 0.001) in surviving patients (n = 59) compared to non-survivors (n = 24). We found an association between serum Bcl2 levels and mortality controlling for age and GCS (OR = 1.149; 95% CI = 1.056–1.251; p = 0.001) and controlling for computer tomography findings (OR = 1.147; 95% CI = 1.056–1.246; p = 0.001). Conclusions This study reports for the first time an association between serum Bcl2 levels and 30-day mortality in TBI patients.

Biological and Classical Prognostic Factors with Impact on Overall Survival in Patients with Early Stage (I/II) Diffuse Large B-Cell Lymphoma: A Study from the Grupo De Estudio Latinoamericano De Linfoproliferativos (GELL)

Background: Diffuse large B-cell lymphoma (DLBCL) is the most common non-Hodgkin lymphoma subtype. Early stage (I/II) disease is seen in up to 30% of all DLBCL cases, and although outcomes in this subgroup have been reported as optimal, relapses can still occur. Prognostic models such as the International Prognostic Index (Miller, NEJM, 1998) continues to be utilized for risk stratification in DLBCL. However, despite its limitations and lack of validation in specific demographic groups such as Latin American patients, no prognostic models exist for the evaluation of limited stage DLBCL. Therefore, we aim to investigate different clinico-epidemiological and laboratory variables and its impact on survival in early stage DLBCL.Methods: We conducted a retrospective study of newly diagnosed patients with early stage DLBCL. Using the Grupo de Estudio Latinoamericano de Linfroproliferativos (GELL) database, we selected patients that had early stage disease, defined as non-bulky stage I or II. The variables analyzed included demographic and clinical variables (e.g., age, ECOG performance status), the International Prognostic Index (IPI), and laboratory variables such as serum albumin, serum lactate dehydrogenase (LDH), serum beta-2-microglobulin, the lymphocyte-monocyte ratio (LMR), the neutrophil-lymphocyte ratio (LNR), and the platelet-lymphocyte ratio (PLR). To determine the variables associated with mortality, univariate and multivariate Cox regression (step-wise type) analysis was performed. Kaplan-Meier and log-rank test were used for survival analysis. Outcomes with a p-value <0.05 were considered statistically significant.Results: We identified 1,375 patients with DLBCL; 503 were identified as early stage DLBCL of whom 498 had sufficient data for analysis. Almost all cases (n=483, 96%) had nodal disease as the primary site, and 15 (4%) extranodal, all within the gastrointestinal tract. There was a slight female predominance (51.8%). The median age at diagnosis was 64 (IQR: 50 -73) with 57.4% older than >65 years. ECOG performance status of <2 was seen in 77.2% of cases; elevated serum LDH in 32.4%; and elevated serum beta-2-microglobulin in 5.6% (n=11/192). Based on previous data, we evaluated and calculated variables that have been suggested as independent negative prognostic factors for overall survival; the proportion of patients with serum albumin <3.5 mg/dL; LMR <2, NLR >4, and PLR >376 was 34.4%, 10.3%, 9.2%, and 4.7% respectively. With a median follow-up of 45 months, the median 5-year overall survival (OS) rate was 72%. The therapy approaches used, response rates and outcomes with these approaches will be presented at the meeting. Results of the univariate and multivariate analysis are summarized in Table 1. We found that age over 65, ECOG performance status, serum albumin level, beta-2-microglobulin level, LDH ratio, LMR, NLR, PLR, and BCL-2 positivity by immunohistochemistry (IHC) were prognostic factors for OS in the univariate analysis. However, in the multivariate analysis, only NLR, serum albumin level and ECOG performance status were independent factor for worse prognosis. Survival rates were significantly shorter in patients with serum albumin <3.5 g/dL (5-year OS of 49% versus 79%, respectively; p<0.0001); NLR >4 (5-year OS of 46% versus 73%, respectively: p=0.0013); and ECOG performance status ≥2 (5-year OS of 51% versus 74%, respectively; p<0.0001) (Figures 1 to 3).Conclusion: In this large cohort of Latin American patients with early stage DLBCL most patients were older than 65, had nodal disease as the primary site, good performance status, with only a third of patients exhibiting elevated LDH. Moreover, we found serum albumin <3.5 g/dL, NLR >4 and ECOG ≥2 as negative prognostic factors for poor survival in early stage DLBCL. We are currently validating our findings in a prospective cohort of Latin American DLBCL patients and to improve clinical decision-making in those deemed at high-risk for early mortality. [Display omitted] DisclosuresOtero: Astra Zeneca: Current Employment. Oliver: Roche: Other: conference support and fees ; Abbvie: Other: conference support and fees . Castillo: Abbvie: Consultancy, Research Funding; BeiGene: Consultancy, Research Funding; Pharmacyclics: Consultancy, Research Funding; Janssen: Consultancy; Roche: Consultancy; TG Therapeutics: Research Funding.

Circulating Bcl-2 concentrations and septic patient mortality

IntroductionThere are not data on blood B-cell lymphoma 2 (Bcl-2) concentrations (one of the antiapoptotic molecules of the Bcl-2 family in the intrinsic apoptosis pathway) in septic patients. Therefore, this study was carried with the aims to explore whether blood Bcl-2 concentrations at diagnosis of sepsis are different in survivor and non-survivor septic patients, are associated with mortality, and are useful for the mortality prediction. MethodsIntensive Care Units from 3 Spanish hospitals participated in this observational and prospective study with septic patients and serum Bcl-2 concentrations at diagnosis of sepsis were determined. Mortality at 30 days was as outcome variable. ResultsWe found that 30-day non-surviving patients (n=81) showed lower serum Bcl-2 levels (p=0.003) than surviving patients (n=140). We found that serum concentrations of Bcl-2<4.4ng/mL were associated with mortality (OR=3.228; 95% CI=1.406–7.415; p=0.006) in the multiple logistic regression analysis, and that showed an area under the curve for mortality prediction of 62% (95% CI=55–68%; p=0.003). ConclusionsIn our study appears novel findings such as higher blood Bcl-2 concentrations in survivor than in non-survivor septic patients, the association between low blood Bcl-2 concentrations and mortality of septic patients, and the ability of blood Bcl-2 concentrations for the prediction of septic patient mortality.

Показатели митохондриального пути апоптоза в сыворотке крови и гомогенате сосудистой стенки у пациентов с атеросклерозом периферических артерий

Aim. Determination of the amount of Bcl2 and Bax apoptosis proteins in the homogenate of the vascular wall and blood serum, and of their relationship in patients with obliterating atherosclerosis of the lower limb arteries (OALLA) with III stage of the disease. Materials and Methods. The study included 12 patients with III stage OALLA according to Pokrovsky-Fontaine classification. After follow-up examination, these patients underwent open surgical interventions on the arteries of the femoral-popliteal segment. According to signed informed consent, during the surgical intervention, the intraoperative samples of all three layers of the vascular wall were taken. A sample of the vessel was crushed, and a homogenate was prepared, in which expression of Bcl2 anti-apoptotic protein and Bax pro-apoptotic protein was determined by ELISA method. Samples of the vascular wall without visible signs of atherosclerosis taken from patients undergoing reconstructive surgery were used as a control for arteries. Initially, before the operation, the studied parameters were determined in blood serum using ELISA method. To determine the reference values of Bcl2 and Bax proteins, healthy volunteers were included in the study. Results. In the homogenate of the arterial wall without atherosclerotic changes (control sample), the amount of Bcl2 protein was 1.26 ng/ml, of Bax 3.8 ng/ml. In the homogenate of the arterial wall in the area of an atherosclerotic plaque, the amount of Bcl2 did not differ from the control sample and was 1.4 ng/ml (p=0.504), and the amount of Bax protein increased to 6.54 ng/ml (p=0.033). In healthy volunteers, Bcl2 and Bax values in serum were 5.2 ng/ml and 15.9 ng/ml, respectively. In patients with OALLA, the amount of Bax protein in blood serum increased to 26.7 ng/ml (p=0.009), with the level of Bcl2 4.96 ng/ml (p=0.761). Correlation analysis showed the relationship between the level of Bcl2 (r=+0.806), Bax (r=+0.699), Вах/Всl2 (r=+0,642) in the homogenate of the vascular wall and in blood serum. Conclusions. In patients with III stage OALLA, the level of pro-apoptotic Bax protein was elevated both in the vascular wall and in the blood serum. The amount of Bcl2 and Bax apoptosis proteins in blood serum reflects their amount in the vascular wall in patients with OALLA.

Blood concentrations of proapoptotic sFas and antiapoptotic Bcl2 and COVID-19 patient mortality

ABSTRACT Background: There are no data on circulating concentrations of sFas (proapoptotic protein of extrinsic pathway) and Bcl2 (antiapoptotic protein of intrinsic pathway) in COVID-19 patients. Thus, our objective study was to determine whether an association exists between serum concentrations of sFas and Bcl2 and COVID-19 patient mortality. Methods: This observational and prospective study of COVID-19 patients was performed in eight Intensive Care Units (ICU) from Canary Islands (Spain). Serum levels of sFas and Bcl2 at ICU admission were determined. Mortality at 30 days was the end-point study. Results: Surviving patients (n = 42) compared to non-surviving (n = 11) had lower APACHE-II (p < 0.001), lower SOFA (p = 0.004), lower serum sFas levels (p = 0.001) and higher serum Bcl2 levels (p < 0.001). Logistic regression showed an association between high serum sFas levels and mortality after controlling for APACHE-II (OR = 1.004; 95% CI = 1.101–1.007; p = 0.01) or SOFA (OR = 1.003; 95% CI = 1.101–1.106; p = 0.004), and between low serum Bcl2 levels and mortality after controlling for APACHE-II (OR = 0.927; 95% CI = 0.873–0.984; p = 0.01) or SOFA (OR = 0.949; 95% CI = 0.913–0.987; p = 0.01). Conclusions: Thus, to the best of our knowledge, this is the first study reporting blood levels of sFas and Bcl2 in COVID-19 patients and its association with mortality.

Micro RNA-148a Targets Bcl-2 in Patients with Non-Small Cell Lung Cancer

Objective:Lung cancer is one of the most prevalent cancers and the leading cause of cancer-related deaths worldwide. MicroRNAs regulate more than 60% of human genes, including tumor suppressor genes and oncogenes. Accordingly, they can affect cancer risk. This study aimed to evaluate the role of serum miR-148a as a non-invasive biomarker in non-small cell lung cancer (NSCLC) patients and to assess the correlation between miR-148a and Bcl-2, as one of its target proteins. Materials and Methods:A total of 50 newly diagnosed NSCLC cases and 30 apparently healthy controls were recruited in this study. MiR-148a level was measured by TaqMan- Real time RT-PCR assay and Bcl-2 level was measured by ELISA. Results:Significant lower expression of serum miR-148a and higher serum Bcl-2 levels were observed in NSCLC patients as compared to the control group (p <0.001 each). A statistically significant inverse correlation was also evident between miR-148a and Bcl-2. Lower miR-148a gene expression level and higher Bcl-2 concentration were found to be associated with advanced tumor stage, lymph node involvement and distant metastasis. Conclusion:MiR-148a could be a possible biomarker for NSCLC and by targeting Bcl-2, it may offer a novel approach for treatment.

Effects of glutamine on exercise-induced fatigue, skeletal muscle oxidation and liver cell apoptosis in rats

Objective: To investigate the effects of glutamine on exercise-induced fatigue, skeletal muscle oxidation and liver cell apoptosis in rats. Methods: Twenty SPF grade SD rats aged at 8 week and weight from 180 to 220 g, were divided into control group and glutamine-treated group after one week of feeding, 10 rats in each group. The rats in the glutamine group were treated with glutamine at the dose of 1.0 g/(kg·d)by intragastric administration, and the rats in control group were administrated with equal volume of normal saline. After 7 days, the exhaustion test was conducted, the content of glutathione (GSH) was detected by high-performance liquid chromatography. Superoxide dismutase (SOD), malondialdehyde (MDA), lactic acid (2-hydroxypropanoic acid (LD) were detected by enzyme-linked immunosorbent assay, and the creatine kinase(CK) was detected by electroluminescence. Activities of CK, Lactate dehydrogenase (LDH), and expression levels of Bcl-2 and Bax mRNA were detected by fluorescence quantitative RT-PCR. Results: The duration of exhaustion in the glutamine group was greater than that in the control group (P＜0.05). The serum glutathione level in the glutamine group was lower than that in the control group (P＜0.05). After exhaustion, the levels of GSH, SOD and MDA in serum and skeletal muscle of the glutamine group were higher than those of the control group significantly differences (P＜ 0.05). The serum Bax mRNA level in the glutamine group was lower than that in the control group significantly (P＜0.05). The serum bcl-2 mRNA level in the glutamine group was higher than that in the control group significantly (P＜0.05). Conclusion: Glutamine can effectively alleviate exercise-induced fatigue in rats, reduce the oxidation degree of skeletal muscle, and decrease the apoptosis rate of liver cells.

Serum Levels of B-cell Lymphoma-2 Anti-Apoptotic Protein and Malignant Middle Cerebral Artery Infarction Mortality

Introduction and GoalThere is scarce and contradictory data on B-cell lymphoma 2 (Bcl2), member of the Bcl-2 antiapoptotic molecules family of intrinsic apoptosis pathway, in ischemic stroke patients. The objective of this study was to determine whether there is an association between blood Bcl2 concentrations and mortality of ischemic stroke patients. Material and MethodsFive Intensive Care Units participated in this prospective and observational study of patients with severe malignant middle cerebral artery infarction (MMCAI). Severe MMCAI was diagnosed when acute infarction was present in 50% or more of said region and with a Glasgow Coma Scale (GCS) score of less than 9 points. Serum samples were collected at the time of MMCAI diagnosis. FindingsHigher serum Bcl2 concentrations (p = 0.001), lower platelet count (p = 0.01) and lower GCS (p = 0.002) were found in non-survivors (n = 28) than in MMCAI survivors (n = 28). Serum Bcl2 levels had an area under the curve for mortality prediction of 75% (95% CI = 62%-88%; p < 0.001). Patients with serum Bcl2 levels > 43.6 ng/mL had higher mortality rate according to Kaplan-Meier analysis (Hazard ratio=10.0; 95% CI = 3.4–29.5; p < 0.001). Multiple logistic regression showed an association between serum Bcl2 and mortality at 30 days (OR = 1.041; 95% CI = 1.006–1.077; p = 0.02) controlling for GCS and platelet count. ConclusionsThis study reports for the first time the higher blood Bcl2 concentrations in non-surviving ischemic stroke patients than in survivors and the association between elevated blood Bcl2 and mortality in ischemic stroke patients.

Prognostic value of circulating Bcl-2 and anti-p53 antibodies in patients with breast cancer: A long term follow-up (17.5 years).

Apoptosis inhibition is a major tumorigenic factor. Bcl-2 dysregulation and TP53 mutation status, which may correlate with autoantibody generation, contribute to impaired apoptosis. This study aimed to investigate the prognostic value of circulating Bcl-2 and anti-p53 antibodies (p53Abs) in a 17.5-year follow-up of breast cancer patients. We also analyzed the correlations of Bcl-2 and p53Abs with various clinicopathological parameters in order to assess their impact on tumor aggressiveness. Serum Bcl-2 and p53Abs levels were analyzed by the enzyme-linked immunosorbent assay (ELISA) in 82 patients with invasive breast cancer and twenty individuals without malignancy. Serum Bcl-2 and p53Abs levels in breast cancer patients were significantly higher than those in controls. Patients with high levels of Bcl-2 (cut-off 200 U/ml) had a poorer prognosis (17.5-year survival) than those with lower Bcl-2 values. In combined analysis the subgroup of patients with elevated p53Abs (cut-off 15 U/ml) and elevated Bcl-2 (cut-offs 124 U/ml and 200U/ml) had the worse prognosis in 17.5-year survival. In correlation analysis p53Abs and Bcl-2 were associated with unfavorable clinicopathological parameters. Our results suggest that breast cancer patients with high serum levels of p53Abs and Bcl-2 present an especially unfavorable group in a long follow-up.