Evaluation the -174G>C Genetic Polymorphism of Interleukin-6 in Iranian Patients with Chronic Lymphocytic Leukemia.

Background & Objective: Interleukin-6 (IL-6) is involved in inflammation and has a significant role in chronic lymphocytic leukemia (CLL) progression. Accordingly, IL-6 level may increase in CLL-affected patients compared to healthy individuals. The -174G>C single nucleotide polymorphism (SNP) in IL-6 promoter region has been related to differences in IL-6 transcription. Therefore, we investigated the possible association of IL-6 polymorphism with CLL. Methods: We examined the -174G>C SNP in IL-6 gene and studied its possible relationship with CLL in affected patients and in healthy controls using Amplification Refractory Mutation System- polymerase chain reaction genotyping method. IL-6 plasma level was measured in both studied groups. Results: According to the results, IL-6 mean plasma concentration was increased significantly in the CLL patients compared to the controls. However, 174G>C genotype of the IL-6 gene was not associated with CLL. Furthermore, there were no significant differences in the distribution of allele and genotype frequencies between the CLL-affected patients and the controls (P>0.05). Conclusion: Our study showed that -174G>C SNP in promotor of IL-6 gene could not be considered a risk factor for CLL. Larger prospective studies should be performed to confirm our results.

Single and Combined Use of Benson Relaxation Technique and Oxygen Therapy on Chemotherapy-Induced Nausea and Vomiting in Gastric Cancer Patients.

BACKGROUND: Nausea and vomiting are the most common complications of chemotherapy encountered by cancer patients. To alleviate these complications and reduce patients' problems, it is necessary to use complementary methods. OBJECTIVE: The present study aimed to investigate the effect of single and combined use of the Benson relaxation technique and oxygen therapy on chemotherapy-induced nausea, vomiting, and retching in patients with gastric cancer. METHODS: This is a single-blind, four-arm, 2 × 2 factorial-design randomized clinical trial, in which a total of 100 patients with gastric cancer were enrolled and assigned to four groups of relaxation therapy, oxygen therapy, combined therapy, and control (n = 25 in each group) using simple random allocation. The intervention program included the application of Benson relaxation technique, supplemental oxygen therapy, and a combination of both. The control group merely received routine care. Data were collected using the Rhodes Index of Nausea and Vomiting Form 2 (INV-2). RESULTS: The results of the Kruskal-Wallis H test showed that there was a statistically significant difference in the mean scores of nausea, vomiting, retching, and acute phase between the four groups (p = 0.001). However, there was a statistically significant difference only in the mean score of retching in this regard for the delayed phase (p = 0.02). CONCLUSION: Overall, the single use of Benson relaxation technique and the combined use of this technique and oxygen therapy were shown to be more effective in managing chemotherapy-induced nausea and vomiting.

Olanzapine enhances the effect of conventional drugs in chemotherapy inducing nausea and vomiting: A randomized clinical trial.

Background: Chemotherapy inducing nausea and vomiting (CINV) is one of the significant side effects of anti-cancer treatment, and its full prevention is a potential challenge. This study was done to specify the effect of olanzapine in this setting. Methods: In this randomized, double-blind, clinical trial study, olanzapine was compared with a placebo in combination with dexamethasone and granisetrone in patients with cancer. Patients in the intervention group received dexamethasone , granisetron and olanzapine. Patients in the control group received a placebo instead of olanzapine. Overall, acute nausea and vomiting prevention were the primary and secondary end points; complete response (no nausea,no vomiting) in the delayed period of chemotherapy was the third end point. Response to treatment was evaluated by the Functional Living Index Emesis (FLIE) questionnaire completion in the first, the third and the fifth of chemotherapy. Results: Percentage reduction in mean±SD nausea and vomiting in the overall phase (0-120 hours) of intervention group compared to the control group respectively were 29.94±2.06, 69.75±2.32 [(57.93% reduction (p<0.001)]. For the acute phase (0-24 hours) were 26.08±2.36, 51.85±2.24 [(47.21% reduction (p<0.001)], for the delayed phase (24-120 hours), were 31.26±2.57, 67.91±2.12 ,[(55.11% reduction;(p<0.001)] respectively. Conclusion: Olanzapine, along with dexamethasone and granisetron, significantly reduced vomiting and nausea in patients undergoing chemotherapy. No adverse event of olanzapine was observed in the patients.

Evaluation of Serum Levels of MicroRNA-200C and ACE2 Gene Expression in Severe and Mild Phases of Patients with COVID-19.

The role of microRNA (miR)200c-3p in regulating ACE2 gene expression in viral and bacterial respiratory diseases has been established. Since ACE2 reduces the acute inflammatory effects in lung diseases and acts as a coronavirus receptor to invade the lung cells, this study investigates the relationship between miR-200c-3p and ACE2 expression in COVID -19 patients. In this study, COVID-19 patients were divided into two groups: mild phase (PCR-positive and mild symptoms) and severe phase (PCR-positive with acute pulmonary symptoms and inflammation). Then, the subjects' demographic, clinical, and paraclinical characteristics were recorded using a prepared checklist. Total RNA was isolated from all samples according to the Trizol kit protocol to evaluate gene expression. Subsequently, the extracted product was analysed for miR-200c expression and ACE2 target gene expression by real-time PCR. The results of the checklist data showed that smoking, cough, and the factors ESR and HCT were statistically significant between the two groups of patients in the mild and acute phases. Also, the mean expression of the miR-200c gene in the mild and acute patients was 1.87±0.70 and 1.87±0.62, respectively, which was not statistically significant. Still, the mean expression of the ACE2 gene, which was 3.96±0.76 and 3.28±0.52 in the mild and acute disease groups, respectively, showed a significant difference between the two groups. This study showed that the expression levels of ACE2 were significantly reduced in people with severe inflammation compared to people with mild inflammation.

Medication errors in hematology-oncology ward by consultation: The role of the clinical pharmacologist.

BACKGROUND: The aim was to describe, evaluate and document the prevention of medication errors by clinical pharmacologist consultations in patients with cancer. METHODS: We assessed the effect of clinical pharmacologist consultation by the acceptance of interventions recommended due to dosage, frequency, duration of therapy errors and drug-drug interactions (DDIs). All medication errors detected by clinical pharmacologist were reported in the format of medical consultation. A documentation template was designed to collect the patient's data (sex, age, and diagnosis), prescriptions written, and drug-specific recommendations. For the descriptive analysis of medication errors, the unit of analysis was the number and percentage of errors. RESULTS: A total of 296 patients included in this study with a median age of 48.67±19.76 years of which 47.30% were females. 936 prescribing errors were detected and recommended for their correction. The specialist physicians accepted 897 of prescribed errors. DDIs that were detected in 66.22% of patients, were the most errors in this group of errors (47%). Improper dose (17.41%) wrong frequency (16.67%) and drug-food interaction (10.26%) were after that. CONCLUSION: Pharmacological consultation in the hematology-oncology ward revealed many medication errors. The trust of physicians in the views of the clinical pharmacologist led to a large part of these errors being accepted and resolved.

Investigation of the Molecular Mechanism of Coagulopathy in Severe and Critical Patients With COVID-19.

Coagulopathy is a frequently reported finding in the pathology of coronavirus disease 2019 (COVID-19); however, the molecular mechanism, the involved coagulation factors, and the role of regulatory proteins in homeostasis are not fully investigated. We explored the dynamic changes of nine coagulation tests in patients and controls to propose a molecular mechanism for COVID-19-associated coagulopathy. Coagulation tests including prothrombin time (PT), partial thromboplastin time (PTT), fibrinogen (FIB), lupus anticoagulant (LAC), proteins C and S, antithrombin III (ATIII), D-dimer, and fibrin degradation products (FDPs) were performed on plasma collected from 105 individuals (35 critical patients, 35 severe patients, and 35 healthy controls). There was a statically significant difference when the results of the critical (CRT) and/or severe (SVR) group for the following tests were compared to the control (CRL) group: PTCRT (15.014) and PTSVR (13.846) (PTCRL = 13.383, p < 0.001), PTTCRT (42.923) and PTTSVR (37.8) (PTTCRL = 36.494, p < 0.001), LACCRT (49.414) and LACSVR (47.046) (LACCRL = 40.763, p < 0.001), FIBCRT (537.66) and FIBSVR (480.29) (FIBCRL = 283.57, p < 0.001), ProCCRT (85.57%) and ProCSVR (99.34%) (ProCCRL = 94.31%, p = 0.04), ProSCRT (62.91%) and ProSSVR (65.06%) (ProSCRL = 75.03%, p < 0.001), D-dimer (p < 0.0001, χ2 = 34.812), and FDP (p < 0.002, χ2 = 15.205). No significant association was found in the ATIII results in groups (ATIIICRT = 95.71% and ATIIISVR = 99.63%; ATIIICRL = 98.74%, p = 0.321). D-dimer, FIB, PT, PTT, LAC, protein S, FDP, and protein C (ordered according to p-values) have significance in the prognosis of patients. Disruptions in homeostasis in protein C (and S), VIII/VIIIa and V/Va axes, probably play a role in COVID-19-associated coagulopathy.

Investigation of p16 protein expression and its association with histopathologic parameters in breast cancer.

We investigated the association between p16 expression and histopathologic parameters including size, neural and vascular invasion, and lymph node involvement in breast cancer. 58 specimens from patients with different grades of breast cancer were included. Hematoxylin and eosin and immunohistochemistry staining for p16 was performed. 5 patients (8.6%) had grade I, 23 (39.7%) had grade II, and 30 (51.7%) had grade III breast cancer. Assessment of the tumor size showed that 5 (8.6%) tumors had a size of ≤2cm, 29 (50%) were between 2-5 cm and 24 (41.4%) had a size of ≥5cm. Moreover, 45 (77.6%) of the included patients had axillary lymph node involvement. Investigation of association between p16 positivity with pathological parameters in three groups with positivity to p16 (1-25%, 26-75%, >75%) showed that there was no association between p16 positivity and other parameters including histologic score (p=0.44), tumor size (p=0.77), neural invasion (p=0.79), perivascular invasion (p=0.98) and the number of involved LNs (p=0.49). From the group including eight patients with >75% p16 positivity, seven (87.5%) were found with neural invasion and two (25%) with perivascular invasion. P16 positivity was not associated with size, neural and vascular invasion, and LN involvement in breast cancer.

Free and hydrogel encapsulated exosome-based therapies in regenerative medicine.

Over the last few decades, mesenchymal stem cells-derived exosomes (MSCs-Ex) have attracted a lot of attention as a therapeutic tool in regenerative medicine. Exosomes are extracellular vehicles (EVs) that play important roles in cell-cell communication through various processes such as stress response, senescence, angiogenesis, and cell differentiation. Success in the field of regenerative medicine sparked exploration of the potential use of exosomes as key therapeutic effectors of MSCs to promote tissue regeneration. Various approaches including direct injection, intravenous injection, intraperitoneal injection, oral administration, and hydrogel-based encapsulation have been exploited to deliver exosomes to target tissues in different disease models. Despite significant advances in exosome therapy, it is unclear which approach is more effective for administering exosomes. Herein, we critically review the emerging progress in the applications of exosomes in the form of free or association with hydrogels as therapeutic agents for applications in regenerative medicine.

Tumor-derived extracellular vesicles: reliable tools for Cancer diagnosis and clinical applications.

BACKGROUND: Studies have recently revealed that almost every type of cells including tumor cells abundantly release small vesicles known as extracellular vesicles (EVs) into the extracellular milieu. EVs carry a repertoire of biological molecules including nucleic acids, proteins, lipids, and carbohydrates and transport their cargo between cells in the vicinity as well as distantly located cells and hence act as messengers of intercellular communication. In this review, we aimed to discuss the tumor-derived exosome biology and the pivotal roles of exosomes in cancer diagnosis and treatment. METHODS: In the present review study, the authors studied several articles over the past two decades published on the kinetics of EVs in tumor environment as well as on the application of these vesicles in cancer diagnosis and therapy. RESULTS: A growing body of evidence indicates that nucleic acids such as microRNAs (miRNAs) transferring by EVs participate to create a conducive tumor environment. As EV-associated miRNAs are tissue-specific and present in most biological fluids, they hold great potential for clinical application in cancer early diagnosis, prognosis, and treatment response. Furthermore, exosomes can serve as drug delivery vehicles transferring miRNAs as well as therapeutic agents to target cells. These nano-vesicles exhibit ideal properties in comparison with the synthetic carriers that attracted scientist's attention in the field of nanotechnology medicine. Scientists have employed different strategies to build exosomes-based drug delivery system. In general, two methods (direct engineering and indirect engineering) are being utilized to produce artificial exosomes. Para-clinical data have confirmed the beneficial effects of engineering exosomes in cancer therapy. CONCLUSION: Exosomal miRNAs hold great promise for clinical application in early diagnosis and treatment of cancers. In addition, in spite of enthusiastic results obtained by engineered exosomes, however, there is an increasing concern over the use of optimal methods for engineering exosomes and the safety of engineered exosomes in clinical trials is still unclear.