Molecular investigations on T cell subsets in patients affected by Hypomorphic DCLRE1C Mutation.

OBJECTIVE: In this study, we explored the expression of transcription factors, cytokines, and co-stimulatory molecules within the helper T (Th) cell subsets (Th1, Th2, Th17 and Treg) of patients with hypomorphic DCLRE1C gene mutations. METHODS: The study comprised eight patients and five controls. Transcription factor and cytokine expressions of Th subsets and co-stimulatory molecules were investigated by qPCR and flow cytometric following T cell stimulation. The findings were compared between patients (non-HSCT) and with hematopoietic stem cell transplantation (HSCT). RESULTS: Flow cytometric analyses; while the Treg rate was significantly lower in non-HSCT than in controls (p = 0.010), the IFN-γ rate was significantly higher in patients than in the control and HSCT groups (p = 0.016, p = 0.022 respectively). Co-stimulatory molecule expressions were significantly lower in non-HSCT than in control (p < 0.001), and there was a significant improvement after HSCT. Post-stimulation qPCR analysis, significant changes were detected in non-HSCT/control, non-HSCT/HSCT and HSCT/control comparisons. CONCLUSIONS: Our study is the first study to molecularly investigate Th cell subsets in hypomorphic DCLRE1C patients. It was determined that abnormalities in Th cell subsets still persisted despite HSCT. There are still many conditions to be explained in these patients, and we believe that our study may shed light on future studies.

Water-soluble Pillar[5]arene-based drug candidates for lung and breast cancer.

The objective of research was to examine the likely anticancer effectiveness of distinct pillar[5] arene derivatives, ws-penta-P[5] and ws-deca-P[5], on breast and lung cancer cell lines in vitro. To achieve this goal, breast cancer (MCF7) cells, lung cancer (A549) cells, healthy cells (HEK293) were utilized. The IC50 dose of ws-penta-P[5] and ws-deca-P[5] was determined using the MTT method. Both treatment (pillar[5] arene applied) and control (pillar[5] arene not applied) groups were established for all three cell lines. Real-time polymerase chain reaction (qPCR) was used to evaluate changes in gene expression following pillar[5] arene treatment. Flow cytometry analysis was used to determine apoptosis and cell cycle arrest. The treatment group and control group results were compared after the study. The results revealed that in both cell lines treated with ws-deca-P[5], proapoptotic gene expressions were upregulated, while antiapoptotic gene expressions and caspase activation gene expressions were down-regulated. The flow cytometry apoptosis and cell cycle analysis in treatment group compared to the control, it was observed that the apoptosis rate increased in the ws-deca-P[5] and ws-deca-P[5] were shown to cause G0/G1 phase arrest in both cell groups. Results from our study that pillar[5] arene derivatives had the potential for treating breast and lung cancer, and more research is required in this area.Communicated by Ramaswamy H. Sarma.

Exploring the combined anti-cancer effects of sodium butyrate and celastrol in glioblastoma cell lines: a novel therapeutic approach.

Glioblastoma, a highly aggressive and lethal brain cancer, lacks effective treatment options and has a poor prognosis. In our study, we explored the potential anti-cancer effects of sodium butyrate (SB) and celastrol (CEL) in two glioblastoma cell lines. SB, a histone deacetylase inhibitor, and CEL, derived from the tripterygium wilfordii plant, act as mTOR and proteasome inhibitors. Both can cross the blood-brain barrier, and they exhibit chemo- and radiosensitive properties in various cancer models. GB cell lines LN-405 and T98G were treated with SB and CEL. Cell viability was assessed by MTT assay and IC50 values were obtained. Gene expression of DNA repair, apoptosis, and autophagy-related genes was analyzed by RT-PCR. Cell cycle distribution was determined using flow cytometry. Viability assays using MTT assay revealed IC50 values of 26 mM and 22.7 mM for SB and 6.77 µM, and 9.11 µM for CEL in LN-405 and T98G cells, respectively. Furthermore, we examined the expression levels of DNA repair genes (MGMT, MLH-1, MSH-2, MSH-6), apoptosis genes (caspase-3, caspase-8, caspase-9), and an autophagy gene (ATG-6) using real-time polymerase chain reaction. Additionally, flow cytometry analysis revealed alterations in cell cycle distribution following treatment with SB, CEL and their combination. These findings indicate that SB and CEL may act through multiple mechanisms, including DNA repair inhibition, apoptosis induction, and autophagy modulation, to exert their anti-cancer effects in glioblastoma cells. This is the first study providing novel insights into the potential therapeutic effects of SB and CEL in glioblastoma.

Evaluation of transcription factors and cytokine expressions of T-cell subsets in CD19 deficiency and their possible relationship with autoimmune disease.

CD19 deficiency is a rare, predominantly antibody deficiency, and there are few studies showing that it can be seen in autoimmune diseases. The aim of study was evaluated to transcription factor and cytokine expressions of helper T (Th)-cell subsets in CD19 deficiency and the possible mechanism role of this factor expression in autoimmune disease. Transcription factor and cytokine expressions of Th1, Th2, Th17, and regulatory T (Treg) cells were investigated by real-time polymerase chain reaction (qPCR) method. In the study, in the patient/control comparison, transcription factor and cytokine expressions of Th1 (T-bet, STAT1, and STAT4) were found to be significantly downregulated, but IFN-γ was significantly upregulated in patients. Th2 factor GATA3, STAT6, IL-4, and IL-5 were significantly downregulated. For Th17, RORγt was downregulated while IL-22 was upregulated. In the heterozygous/control comparison, there was no significant change in gene expressions other than IL-5. T-bet, STAT1, GATA3, IL-4, RORγt, FoxP3, and TGF-ß were significantly downregulated in the patient/heterozygous comparison. It was revealed for the first time that the expression of the transcription factors and cytokines in CD19 deficiency. These findings might be showing the predominance of Th1 factors and suppressed Treg factors which could be related with autoimmunity in CD19 deficiency.

Effect of intensive training on immune system cells in elite female weightlifters

SUMMARY OBJECTIVE: This study aimed to investigate the effects of intense weightlifting training on lymphocyte and natural killer cell subgroups, which are the major cells of the immune system, in elite female weightlifters. METHODS: A total of 20 elite female weightlifters were evaluated using flow cytometry before training (pre-T), immediately after training (post-T), and after a 120-min rest period (rest-T). RESULTS: Post-T and rest-T showed significant decreases in helper T (Th) and cytotoxic T compared with pre-T (p=0.045, p<0.001 and p=0.05, p<0.001, respectively). B and natural killer cells were higher in post-T and rest-T than in pre-T. The increase in B cells was significant in pre-T/rest-T (p<0.001) but not in pre-T/post-T (p=0.122). Intense training significantly increased natural killer cells in both post-T and rest-T (p<0.001). CD56bright and CD56dim natural killer cell subgroups were significantly lower in post-T and rest-T than in pre-T (p=0.005, p=0.006 and p<0.001, p=0.004, respectively). CONCLUSION: This study shows that intense weightlifting alters peripheral lymphocyte and natural killer subgroup ratios, being the first investigation in this field.

Effect of intensive training on immune system cells in elite female weightlifters.

OBJECTIVE: This study aimed to investigate the effects of intense weightlifting training on lymphocyte and natural killer cell subgroups, which are the major cells of the immune system, in elite female weightlifters. METHODS: A total of 20 elite female weightlifters were evaluated using flow cytometry before training (pre-T), immediately after training (post-T), and after a 120-min rest period (rest-T). RESULTS: Post-T and rest-T showed significant decreases in helper T (Th) and cytotoxic T compared with pre-T (p=0.045, p<0.001 and p=0.05, p<0.001, respectively). B and natural killer cells were higher in post-T and rest-T than in pre-T. The increase in B cells was significant in pre-T/rest-T (p<0.001) but not in pre-T/post-T (p=0.122). Intense training significantly increased natural killer cells in both post-T and rest-T (p<0.001). CD56bright and CD56dim natural killer cell subgroups were significantly lower in post-T and rest-T than in pre-T (p=0.005, p=0.006 and p<0.001, p=0.004, respectively). CONCLUSION: This study shows that intense weightlifting alters peripheral lymphocyte and natural killer subgroup ratios, being the first investigation in this field.

Molecular investigation of the effect of weightlifting training on helper T cell subsets in female weightlifting athletes: an immune profiling panel.

BACKGROUND: In this study, it was aimed to molecularly investigate the changes in the helper T (Th) cell subgroups of intense weightlifting training. For this purpose, transcription factor and cytokine expressions of Th1, Th2, Th17, and regulator T cell (Treg) cells were evaluated. METHODS: Eight elite weightlifting athletes were included in the study. Within the scope of the study, transcription factor and cytokine expressions of Th cell subgroups were evaluated by real-time polymerase chain reaction (qPCR) method before training, after intense training with 90-100% capacity, and after 120 minutes of rest from training. RESULTS: As a result of the study, when the pre-training and post-training expressions were compared, an increase in Th1 and Th2 cell factors and a decrease in Th17 and Treg cell-related expressions were detected. These changes were statistically significant (P<0.05). The changes in expressions after training and after 120 minutes of rest were not statistically significant (P>0.05). CONCLUSIONS: Changes have been detected in Th cell subgroups due to intense weightlifting training, and these changes are the first study conducted with female weightlifters.

Impacts of potential anticancer agents based on pillar[5]arene for head and neck squamous cell carcinoma cells.

PURPOSE: This study was conducted to investigate impacts of potential anticancer (associated with apoptosis and caspase pathways) of two newly synthesized derivatives of pillar[5]arene, named as d-Q-P5 and p-Q-P5, on Squamous cell carcinomas of the head and neck (HNSCC) cells. MATERIALS AND METHODS: The MTT method was used to determine the IC50 doses of the derivatives on HNSCC cells, and the changes in gene expression were analyzed by real-time polymerase chain reaction (qPCR). The apoptosis change was confirmed by flow cytometry analysis. RESULTS: The results showed that the d-Q-P5 and p-Q-P5 effectively inhibited the proliferation of the cells by upregulating proapoptotic genes (Bax, Bad, p53, Bak, and Apaf-1) and genes involved in the caspase pathway (Casp2, Casp3, and Casp9), while downregulating the antiapoptotic gene (Bcl-2). CONCLUSIONS: This study is the first to demonstrate the potential anticancer effects of these two agents on HNSCC cells by positively regulating apoptosis gene expression.

Effective anticancer agents based-on two Pillar[5]arene derivatives for pancreas cancer cell lines: synthesis, apoptotic effect, caspase pathway.

This study aimed to evaluate the possible anticancer effects of two different pillar[5]arene derivatives (5Q-[P5] and 10Q-P[5]) on two different pancreatic cancer cell lines in vitro. For this purpose, changes in the expression of major genes that play a role in apoptosis and caspase pathways were investigated. Panc-1 and BxPC-3 cell lines were used in the study and the cytotoxic dose of pillar[5]arenes was determined by the MTT method. Changes in gene expression after pillar[5]arenes treatment were evaluated by real-time polymerase chain reaction (qPCR). Apoptosis was studied by flow cytometry. As a result of analysis, it was determined that proapoptotic genes and genes involved in major caspase activation were upregulated and antiapoptotic genes were down-regulated in Panc-1 cell line treated with pillar[5]arenes. Flow cytometric apoptosis analysis also showed an increased apoptosis rate in this cell line. On the contrary, although MTT analysis showed cytotoxic effect in BxPC-3 cell line treated with two pillar[5]arene derivatives, the apoptosis pathway was not active. This suggested that it may activate different death pathways for BxPC-3 cell line. Thus, it was first determined that the pillar[5]arene derivatives reduced cancer cell proliferation on pancreatic cancer cells.

The effect of intermittent diet and/or physical therapy in patients with chronic low back pain: A single-blinded randomized controlled trial.

BACKGROUND AND PURPOSE: This study aimed to investigate the effect of intermittent diet and/or physical therapy in patients with chronic low back pain. MATERIALS AND METHODS: Sixty sedentary volunteers with chronic low back pain participated in the study. Body weight and body mass index (BMI) were measured. Pain severity was assessed using Visual Analogue Scale (VAS) and Leeds Assessment of Neuropathic Symptoms and Signs (LANSS), while assessment of disability was done using Barthel Index (BI). RESULTS: The weight and BMI were reduced after treatment with diet only and diet plus physical therapy (p < 0.001). The pain severity was reduced in all the treated groups (p < 0.001), while BI was increased in the group treated with only physical therapy (p < 0.001). CONCLUSION: The present study indicated that intermittent diet and/or physical therapy are beneficial to patients with chronic low back pain in terms of pain sensation and daily activities.

Evaluation of coagulation with TEG in patients diagnosed COVID-19.

BACKGROUND: A high D-dimer level may indicate the risk of coagulopathy and mortality in COVID-19 patients. T hromboelastography (TEG) is a test that evaluates clot formation and fibrinolysis in real-time, unlike routine coagulation tests. The study aimed to investigate the coagulation process with TEG in patients diagnosed with COVID-19. METHODS: The study was performed at our university hospital, chest diseases outpatient clinic as a cross-section study. A total of 51 patients with 23 high D-dimer levels group (HDG) and 28 low D-dimers group (LDG) were included in the study. TEG analysis was performed at the pretreatment evaluation in these two groups. RESULTS: D-dimer and fibrinogen levels of the HDG were higher than those of the LDG (550 vs. 90 ng/mL, p < 0.001; 521 vs. 269 mg/ dL, p < 0.001, respectively). In TEG analysis, HDG's R and K values were lower than LDG, and HDG's Angle, MA, and CI values were higher than LDG (p = 0.037; p < 0.001; p < 0.001; p < 0.001; p < 0.001, respectively). ROC curve analysis suggested that the optimum TEG parameters cut-off points for thrombosis risk were as below: for K was ≤2.1 min, for R was ≤6.1 min, for Angle was >62°, MA was 60.4 mm.

Clinical Evaluation of Acute Pancreatitis Caused by SARS-CoV-2 Virus Infection.

INTRODUCTION: Coronavirus 2019 disease (COVID-19), caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has spread to more than 200 countries worldwide. We aimed to present acute pancreatitis (AP) cases caused by SARS-CoV-2 viral infection. METHODS: The study was conducted retrospectively between April 2020 and June 2020 in Necmettin Erbakan University Meram, Medical Faculty Hospital, and 150 hospitalized patients diagnosed with COVID-19 were included. The degree of acute pancreatitis was determined according to the Atlanta classification. Organ failures of the patients were evaluated in terms of respiratory, cardiovascular, and nephrology according to the modified Marshall scoring (MMS) system, and CTSI (Balthazar score) and Imrie score were determined. Modified Marshall score ≥ 2 was considered organ failure. RESULTS: A total of 29 patients were diagnosed with acute pancreatitis. All 29 patients with pancreatitis had respiratory failure during hospitalization. After the diagnosis of pancreatitis, there was no change in respiratory failure. According to the Atlanta classification, 19 patients had mild AP and 10 patients had moderate AP. Patients with acute pancreatitis were scored according to the CTSI (Balthazar score), and there were no patients with ≥6 severe pancreatitis. The CTSI score of 4 patients was 3. In addition, the Imrie score of the patients was determined and 8 patients with Imrie score ≥ 3 were identified. CONCLUSION: The rate of pancreatic damage in SARS-CoV-2 infection was found to be 19% (n = 29) in our study. In our study, we highlight acute pancreatitis as a complication associated with COVID-19 and the importance of pancreatic evaluation in patients with COVID-19 and abdominal pain is demonstrated.