The effect of mesenchymal stem cells administration on DNA repair gene expressions in critically ill COVID-19 patients: prospective controlled study.

When the studies are evaluated, immunomodulatory effect of MSCs, administration in critically ill patients, obstacle situations in use and side effects, pulmonary fibrosis prevention, which stem cells and their products, regeneration effect, administration route, and dosage are listed under the main heading like. The effect of MSC administration on DNA repair genes in COVID-19 infection is unknown. Our aim is to determine the effect of mesenchymal stem cells (MSCs) therapy applied in critically ill patients with coronavirus infection on DNA repair pathways and genes associated with those pathways. Patients (n = 30) divided into two equal groups. Group-1: Patients in a critically ill condition, Group-2: Patients in critically ill condition and transplanted MSCs. The mechanism was investigated in eleven genes of five different pathways; Base excision repair: PARP1, Nucleotide excision repair (NER): RAD23B and ERCC1, Homologous recombinational repair (HR): ATM, RAD51, RAD52 and WRN, Mismatch repair (MMR): MLH1, MSH2, and MSH6, Direct reversal repair pathway: MGMT. It was found that MSCs application had a significant effect on 6 genes located in 3 different DNA damage response pathways. These are NER pathway genes; RAD23 and ERCC1, HR pathway genes; ATM and RAD51, MMR pathway genes; MSH2 and MSH6 (p < 0.05). Two main points were shown. First, as a result of cellular damage in critical patients with COVID-19, DNA damage occurs and then DNA repair pathways and genes are activated in reaction to this situation. Second, administration of MSC to patients with COVID-19 infection plays a positive role by increasing the expression of DNA repair genes located in DNA damage pathways.

Diagnostic Value of Serum Cytokines in Predicting a Complicated Acute Appendicitis.

The diagnostic role of serum cytokines depends on the etiology and pathogenesis of acute appendicitis but the clinical significance of these cytokines in the differential diagnosis of complicated acute appendicitis remains unclear. To investigate the prediction of progression and diagnostic values of interleukin-6, interleukin-1 beta, and tumor necrosis factor-alpha in complicated acute appendicitis. This study was conducted in 100 patients with a definitive diagnosis of acute appendicitis and 20 individuals assigned for the control group. Venous blood was collected to assess biochemical tests, as well as interleukin-6, interleukin-1ß, and tumor necrosis factor-α levels. Serum levels of all parameters were dramatically higher in the complicated group compared with uncomplicated. Duration of hospitalization, rates of postoperative infection, intraabdominal abscess, and re-hospitalization were higher in complicated group. Cut-off points of WBC, CRP, NLR, interleukin-6, interleukin-1ß and tumor necrosis factor-α were 13.5x103/µL, 1.92 mg/dL, 6.09, 23.4 pg/mL, 5.6 pg/mL and 24 pg/mL (p=0.0014, p<0.001, p=0.009, respectively and p<0.001 for the rest). AUC of interleukin-6 was larger than AUCs of all other parameters, suggesting the highest predicting power of interleukin-6 among other parameters. Serum interleukin-6, interleukin-1ß, and tumor necrosis factor-α levels are valuable diagnostic parameters to predict a complicated acute appendicitis.

The importance of inflammatory markers in detection of complications in patients with gastric cancer undergoing the Enhanced Recovery After Surgery (ERAS) protocol: a prospective cohort study.

Introduction: Early diagnosis reduces mortality and morbidity rates in gastrointestinal system (GIS) anastomoses. Aim: The aim of the present study was to investigate the importance of some substances that were used to detect major complications early in patients who were treated in line with the Enhanced Recovery After Surgery (ERAS) protocol for gastric cancer. Factors included in the study were interleukin-1ß (IL-1ß), tumor necrosis factor-α (TNF-α), C-reactive protein (CRP), procalcitonin (PCT) and white blood cell (WBC). Material and methods: A hundred and twenty patients who underwent laparoscopic subtotal or total gastrectomy for gastric cancer in accordance with the ERAS protocol between January 2018 and December 2019 were included in this prospective study. Blood values of IL-1ß, TNF-α, CRP, PCT, and WBC on the third and fifth post-operative days (POD) were measured for diagnosing major complications. Results: Major complications occurred in 12 (10%) patients. Third POD and fifth POD measurements of IL-1ß, TNF-α, CRP, PCT were statistically significantly higher than those in the non-complicated group, whereas WBC was not. In addition, in the group with complications, statistically significant changes of the blood levels of IL-1ß, TNF-α, CRP, and PCT between the 3rd and 5th days were detected (p = 0.008, p = 0.001, p = 0.004, p = 0.001 respectively). Conclusions: IL-1ß, TNF-α, CRP, and PCT can be used in the early detection of major complications in gastric cancer patients undergoing the ERAS protocol. Imaging methods should be used in patients with high levels of these inflammatory substances on the third and fifth POD.

Measurement of Advanced Glycation End Products Could Be Used as an Indicator of Unhealthy Nutrition for Colorectal Cancer Risk.

The main culprit behind most cancers is the accumulation of reactive oxygen species. Glyoxal (GO) and methylglyoxal (MGO) are reactive intermediates created by food processing and they are precursors of advanced glycation end products (AGE) that cause glycative stress. We aimed to evaluate the relationship between AGE levels of healthy volunteers and treatment-naive patients diagnosed with colorectal cancer. The study consisted of patients diagnosed with colorectal cancer and healthy volunteers who underwent routine colonoscopy. The study was conducted with a total of 42 cases, 47.6% (n = 20) female. The ages of the participants in the study ranged from 41 to 82 years, and the mean was 60.57 ± 10.78 years. The GO and MGO values of the patient group were found to be significantly higher than those of the control group (p = 0.007, p = 0.001, respectively). The risk of colorectal cancer was 22 and 57 times higher in individuals with GO and MGO values above 1.25 µg/mL and 0.0095 µg/mL, respectively. The blood AGE level is closely related to diet, and it can be decreased through the appropriate improvement of diet. Thus, the measurement of AGE can be used to predict whether a person's nutrition is healthy or unhealthy and prevent increased risk of colorectal cancer.

The Effect of Polypharmacy on the Charlson Comorbidity Index and Katz Index in Aging People with and without Diabetes Mellitus.

OBJECTIVE: The prevalence of diabetes mellitus is growing worldwide, as well as in the aging population, and its comorbidity and mortality rates are higher in aging people than they are in young people. It has been observed that the number of drugs used increases in aging patients, especially in diabetic patients. This study aimed to investigate the relationship between polypharmacy and modified Charlson Comorbidity Index (CCI) and Katz Index of Independence in Activities of Daily Living (Katz ADL) scores in aging diabetic and non-diabetic patients. MATERIALS AND METHODS: This prospective study included 184 diabetic and 62 non-diabetic subjects who were ≥65 years old. Comorbidity was determined with CCI, and dependency on daily basic activities was assessed with Katz ADL. RESULTS: CCI and the number of drugs were significantly higher in diabetic groups (P = .001). In all subjects and in the diabetic group, there was a negative correlation between CCI and Katz ADL (r = -0.343, P = .001; r = -0.383, P = .001, respectively); there was a positive correlation between CCI and number of drugs (r = 0.430, P = .001; r = 0.248, P = .001, respectively). CONCLUSION: We found an increase in the number of drugs taken by the aging patients, positively correlated with the CCI score. The increase in the number of drugs used is closely related to the insufficiency in daily life activity and comorbidity, and this predicts 10-year survival. Patients should be directed to special centers or physicians who will be scheduled for multidisciplinary treatment for the prevention of polypharmacy, especially in the aging.

The importance of presepsin value in detection of gastrointestinal anastomotic leak: a pilot study.

BACKGROUND: Early diagnosis of anastomotic leakage is the most important factor in reducing its morbidity and mortality. Anastomotic integrity monitoring of the leukocyte count (WBC), C-reactive protein (CRP), and neutrophil-lymphocyte ratio (NLR) are commonly used laboratory parameters. The availability of follow-up presepsin anastomotic integrity was investigated in this study. MATERIALS AND METHODS: This study included patients who had gastrointestinal anastomosis due to major abdominal surgery between January 2016 and February 2017. Blood samples were collected to determine the WBC, CRP, NLR, and presepsin values before the anastomosis was performed and then taken on postoperative days 1, 3, and 5. RESULTS: This is a prospective nonrandomized study with 100 consecutive patients enrolled in the anastomosis group (male/female, 42:58). WBC, CRP, NLR, and presepsin values are based on certain days in the complication group, and the complication group increased with statistical significance. Presepsin had a specificity of 98.63% in determining anastomotic leak. CONCLUSIONS: Presepsin can be used as a supplemental marker with CRP and NLR for anastomotic integrity.

Vitamin D3 inhibits the proliferation of T helper cells, downregulate CD4+ T cell cytokines and upregulate inhibitory markers.

1 α, 25-dihydroxyvitamin D3 (VitD3) has been suggested to have strong modulatory properties in the immune system. Researchers in the present study primarily aimed to understand the effect of VitD3 on human CD4+ T cell proliferation in antigen presenting cells (APCs) free condition in vitro. The effect of VitD3 on intracellular cytokine responses trend to Th1, Th2, Th17 and Th22 was evaluated using the flow cytometry. Moreover the effect of VitD3 on the expression of inhibitory markers such as PD1, PD-L1, and CTLA4 which are induced upon polyclonal T cell receptor (TCR) activation on CD4+ T cells, was assessed. We observed that the stimulation of CD4+ T cells with VitD3, suppressed proliferation capacity, enhanced the expression of PD1, PD-L1 and CTLA4 inhibitory markers on CD4+ T cells, and diminished the percentage of pro-inflammatory cytokines including, IFN-γ, IL-17, and IL-22 except IL-4 in CD4+ T cells. The data suggested a potential insight into the consideration of VitD3 in the prevention/control of pro-inflammatory immune response/autoimmune disorders.

Serum Presepsin Levels Are Not Elevated in Patients with Controlled Hypertension.

INTRODUCTION: Hypertension (HT) is a common serious condition associated with cardiovascular morbidity and mortality. The pathogenesis of HT is multifactorial and has been widely investigated. Besides the vascular, hormonal, and neurological factors, inflammation plays a crucial role in HT. Many inflammatory markers such as C-reactive protein, cytokines, and adhesion molecules have been studied in HT, which supported the role of inflammation in the pathogenesis of HT. Presepsin (PSP) is a novel biomarker of inflammation. Therefore, the potential relationship between PSP and HT was investigated in this study. METHODS: Forty-eight patients with controlled HT and 48 controls without HT were included in our study. Besides routine clinical and laboratory data, PSP levels were measured in peripheral venous blood samples from all the participants. RESULTS: PSP levels were significantly lower in patients with HT than in controls (144.98 ± 75.98 versus 176.67 ± 48.12 pg/mL, p = 0.011). PSP levels were positively correlated with hsCRP among both the patient and the control groups (p = 0.015 and p = 0.009, resp.). However, PSP levels were not correlated with WBC among both groups (p = 0.09 and p = 0.67, resp.). CONCLUSIONS: PSP levels are not elevated in patients with well-controlled HT compared to controls. This result may be associated with anti-inflammatory effects of antihypertensive medicines.

The role of T regulatory cells in immunopathogenesis of myasthenia gravis: implications for therapeutics.

T regulatory cells (Tregs) are crucial for the development of self-tolerance and are the major focus in many studies interpreting the pathogenesis of myasthenia gravis (MG), an autoimmune-based disease. In normal conditions, Tregs regulate the immune responses, while impaired regulatory function of these cells can lead to autoimmunity. Recent studies have confirmed that the thymic and peripheral blood CD4(+)CD25(+) Tregs of MG are defective in functions and/or in numbers, which are associated with disease severity; approaches to correct the defects of these Tregs may be promising in the treatment of MG. This review discusses recent studies on characteristics, quantitative and qualitative changes of Tregs and possible mechanisms that are involved in the impairment of these cells in MG pathogenesis. In addition, new approaches inducing Treg generation that are currently being investigated as therapies for MG, will be discussed as well as proposed approaches for future therapies.

A stimulatory role of ozone exposure on human natural killer cells.

Ozone is claimed to have beneficial effects. While studies revealed the safe therapeutic use of ozone, there are conflicting results for the link between immune system and ozone encounter. Natural killer (NK) cells are important sentinels of immunity with their cytotoxic activity and immune-regulatory potentials. This study aimed to investigate the effects of direct ozone encountering on human immune system, at cellular level. Survival, proliferative capacity and subset content of peripheral blood mononuclear cells (PBMC) were analysed. PBMC of healthy donors (n=5, mean age: 27±6 years) were exposed to 1, 5, 10 and 50 µg/mL doses of medical ozone, directly injected into culture wells, once, initially. 1 and 5 µg/mL doses didn't show toxic effects while 10 and 50 µg/mL doses were toxic. PBMC were cultured for 5 days following 1 and 5 µg/mL ozone encountering. 1 µg/mL dose increased numbers of CD3-CD16+/56+ NK cells among PBMC. Following stimulation with ozone, no difference was observed in basal and phytohemaglutinin-stimulated proliferative capacity. 1 and 5 µg/mL doses of ozone were found to increase NK cytotoxicity. These data indicates influential effects of transient ozone exposure on NK cells, which in turn may have a role in control of immune responses.