Mesenchymal stem cell-derived exosomes for management of prostate cancer: An updated view.

Prostate cancer represents the second most prevalent form of cancer found in males, and stands as the fifth primary contributor to cancer-induced mortality on a global scale. Research has shown that transplanted mesenchymal stem cells (MSCs) can migrate by homing to tumor sites in the body. In prostate cancer, researchers have explored the fact that MSC-based therapies (including genetically modified delivery vehicles or vectors) and MSC-derived exosomes are emerging as attractive options to improve the efficacy and safety of traditional cancer therapies. In addition, researchers have reported new insights into the application of extracellular vesicle (EV)-MSC therapy as a novel treatment option that could provide a more effective and targeted approach to prostate cancer treatment. Moreover, the new generation of exosomes, which contain biologically functional molecules as signal transducers between cells, can simultaneously deliver different therapeutic agents and induce an anti-tumor phenotype in immune cells and their recruitment to the tumor site. The results of the current research on the use of MSCs in the treatment of prostate cancer may be helpful to researchers and clinicians working in this field. Nevertheless, it is crucial to emphasize that although dual-role MSCs show promise as a therapeutic modality for managing prostate cancer, further investigation is imperative to comprehensively grasp their safety and effectiveness. Ongoing clinical trials are being conducted to assess the viability of MSCs in the management of prostate cancer. The results of these trials will help determine the viability of this approach. Based on the current literature, engineered MSCs-EV offer great potential for application in targeted tumor therapy.

Immunoregulatory effects of nanocurcumin in inflammatory milieu: Focus on COVID-19.

The use of natural compounds, such as curcumin, to treat infections caused by bacteria, viruses, fungi, parasites, inflammatory diseases, and various types of cancer is an active and dynamic area of research. Curcumin has a long history of use in the food industry, and there is currently a growing interest in its therapeutic applications. Numerous clinical trials have consistently shown that curcumin, a polyphenolic compound, is safe and well-tolerated even at high doses. There is no toxicity limit. However, the clinical efficacy of curcumin has been limited by its constraints. However, scientific evidence indicates that the use of adjuvants and carriers, such as nanoparticles, exosomes, micelles, and liposomes, can help overcome this limitation. The properties, functions, and human benefits of using nanocurcumin are well-supported by scientific research. Recent evidence suggests that nanocurcumin may be a beneficial therapeutic modality due to its potential to decrease gene expression and secretion of specific inflammatory biomarkers involved in the cytokinestorm seen in severe COVID-19, as well as increase lymphocyte counts. Nanocurcumin has demonstrated the ability to improve clinical manifestations and modulate immune response and inflammation in various autoinflammatory diseases. Additionally, its efficacy, affordability, and safety make it a promising replacement for residual cancer cells after tumor removal. However, further studies are necessary to evaluate the safety and efficacy of nanocurcumin as a new therapeutic in clinical trials, including appropriate dosage, frequency, and duration.

Bilateral inferior petrosal sinus sampling: validity, diagnostic accuracy in lateralization of pituitary microadenoma, and treatment in eleven patients with Cushing's syndrome - a single-center retrospective cohort study.

BACKGROUND: This single-center retrospective cohort study aimed to describe the findings and validity of Bilateral inferior petrosal sinus sampling (BIPSS) in the differential diagnosis of patients with ACTH-dependent Cushing's syndrome (CS). METHODS: Eleven patients underwent BIPSS due to equivocal biochemical tests and imaging results. Blood samples were taken from the right inferior petrosal sinus (IPS), left IPS, and a peripheral vein before and after stimulation with desmopressin (DDAVP). ACTH and prolactin levels were measured. The diagnosis was based on the ACTH ratio between the IPS and the peripheral vein. Also, lateralization of pituitary adenoma in patients with Cushing's disease (CD) was predicted. No significant complications were observed with BIPSS. RESULTS: Based on the pathology report, eight patients had CD, and three had ectopic ACTH syndrome (EAS). Unstimulated BIPSS resulted in a sensitivity of 87.5%, specificity of 100%, PPV of 100%, NPV of 75%, and accuracy of 91%. Stimulated BIPSS resulted in a sensitivity of 100%, specificity of 100%, PPV of 100%, NPV of 100%, and accuracy of 100%. However, pituitary magnetic resonance imaging (MRI) had a lower diagnostic accuracy (sensitivity:62.5%, specificity:33%, PPV:71%, NPV:25%, accuracy:54%). BIPSS accurately demonstrated pituitary adenoma lateralization in 75% of patients with CD. CONCLUSIONS: This study suggests that BIPSS may be a reliable and low-complication technique in evaluating patients with ACTH-dependent CS who had inconclusive imaging and biochemical test results. The diagnostic accuracy is improved by DDAVP stimulation. Pituitary adenoma lateralization can be predicted with the aid of BIPSS.

Vitamin C supplementation lowers advanced glycation end products (AGEs) and malondialdehyde (MDA) in patients with type 2 diabetes: A randomized, double-blind, placebo-controlled clinical trial.

This study evaluated how daily vitamin C administration impacts systemic oxidative stress and inflammation and its safety in T2D patients. This randomized, double-blinded, placebo-controlled, parallel-arm clinical trial included 70 patients with T2D. They were allocated to receive either 500 mg/day of vitamin C or a matching placebo for 8 weeks. Of the 70 subjects assigned to the trial, 57 were included in the statistical analysis (vitamin C: n = 32, placebo: n = 25). Inflammatory and oxidative markers, including advanced glycation end products (AGEs), malondialdehyde (MDA), advanced oxidation protein products (AOPP), oxidized low-density lipoprotein (ox-LDL), highly sensitive C-reactive protein (hs-CRP), tumor necrosis factor-α (TNF-α), and ferric reducing ability of plasma (FRAP) were measured at baseline and the end of the trial. In addition, vitamin C tolerance was evaluated. A nutritionist visited all participants for a standard diabetic regimen. Following vitamin C supplementation, the serum levels of MDA (p-value < .001) and AGEs (p-value = .002) demonstrated a significant decrease after controlling for multiple confounders, including age, blood pressure, waist circumference, HbA1C, TG, and LDL-C, while no significant changes were observed for AOPP (p-value = .234) and ox-LDL (p-value = .480). The FRAP showed an increasing trend as an antioxidant marker but was not statistically significant (p-value = .312). The hs-CRP and TNF-α had no significant changes (p-value: .899 and .454, respectively). Also, no major adverse events were observed. Vitamin C supplementation may be beneficial in reducing AGEs and MDA in patients with T2D.

Effects of acupressure on intestinal function in patients with coronary artery bypass graft surgery: a randomized clinical trial.

Aim: This study aimed to determine the effects of acupressure on the intestinal function of patients undergoing Coronary Artery Bypass Graft (CABG) surgery. Background: Studies indicated that cardiovascular patients are prone to constipation. Acupressure is one of the therapeutic and palliative approaches that can be used by doctors, nurses, and even patients themselves. Methods: The present three-group randomized clinical trial study was conducted on 90 patients undergoing CABG surgery. In the intervention group, 48 hours after surgery the patients received acupressure points LI4 and ST25 twice a day (10 am and 6 pm) for three sequential days. In the sham group, the patients received acupressure at a 1.5 cm distance from the LI4-ST25 points, and the patients in the control group received only the usual care. This research used a demographic and medical information questionnaire, Rome IV scale, Bristol stool scale, symptom registration checklist, and daily excretion assessment checklist. The intestinal function indices were completed 24 hours after surgery (before intervention), 48, 72, 96, and 120 hours after surgery. Results: All three intervention, sham, and control groups were without defecation in 24 hours (before intervention) and 48 hours after surgery. There was a significant difference between the three intervention, sham, and control groups in the number of stools after 72 hours, 96 hours, and 120 hours after the intervention (p<0.001). Also, a significant difference was observed among the three groups in terms of stool consistency 96 hours after the start of the intervention (p=0.032) and 120 hours after the start of the intervention (p<0.001). Conclusion: The results showed that patients had a significant improvement in the number of bowel movements and stool consistency in the intervention group. In acute conditions, acupressure on LI4-ST25 points can positively affect intestinal function when patients are hospitalized in the intensive care unit.

Lipid profile, ox-LDL, and LCAT activity in patients with endometrial carcinoma and type 2 diabetes: The effect of concurrent disease based on a case-control study.

Background and Aim: The role of lecithin: cholesterol acyltransferase (LCAT) and oxidized low-density lipoprotein (ox-LDL) in endometrial cancer (EC) or EC with concurrent type 2 diabetes is still unclear. This study investigated the LCAT activity, ox-LDL, and lipid profile in EC patients with or without type 2 diabetes and compared them with healthy individuals and patients with type 2 diabetes alone. Methods: In this cross-sectional, case-control study, 93 female participants were recruited. The participants were divided into four groups, including EC with type 2 diabetes (n = 19), EC without type 2 diabetes (n = 17), type 2 diabetes (n = 31), and healthy controls (n = 26). Sociodemographic information, the LCAT activity, triglyceride (TG), total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and ox-LDL levels were collected. One-way analysis of variance and analysis of covariance, Student's t-test, Mann-Whitney U-test, and χ 2-test were used to compare demographic features and laboratory results among studied groups. Regression analyses were also performed to evaluate the interaction effect between EC and type 2 diabetes on serum LCAT activity. Results: The LCAT activity was significantly lower, and ox-LDL levels were significantly higher in all patient groups compared to the healthy controls (p < 0.001). EC patients had significantly lower LCAT activity and higher ox-LDL levels than type 2 diabetes and healthy groups (p < 0.05). Higher levels of TG and lower levels of HDL-C were observed in all patient groups compared to the healthy group (all p < 0.001). Patients with EC and concomitant type 2 diabetes had significantly lower serum LDL-C levels than healthy and type 2 diabetes groups (p < 0.05). Conclusions: The combination of EC and type 2 diabetes had a subadditive effect on LCAT activity and ox-LDL level. The lowest LCAT activity and the highest ox-LDL levels were observed in patients with EC and concurrent type 2 diabetes.

Using Electronic Medical Records and Clinical Notes to Predict the Outcome of Opioid Treatment Program.

Opioid addiction is a serious public health problem in the US, and this study aimed to explore how natural language processing (NLP) can be used to identify factors that contribute to distress in individuals with opioid addiction, and then use this information along with structured data to predict the outcome of opioid treatment programs (OTP). The study analyzed medical records data and clinical notes of 1,364 patients, out of which 136 succeeded in the program and 1,228 failed. The results showed that several factors influenced the success of patients in the program, including sex, race, education, employment, secondary substance, tobacco use, and type of residences. XGBoost with down sampling was the best model. The accuracy of the model was 0.71 and the AUC score was 0.64. The study highlights the importance of using both structured and unstructured data to evaluate the effectiveness of OTP.

Endurance Exercise Training Attenuates the Waterpipe Smoke Inhaling-Induced Learning and Memory Impairment in Rats: Role of Neurotrophic Factors and Apoptotic System.

INTRODUCTION: The increasing prevalence of waterpipe tobacco smoking (WTS) and its detrimental effects on memory function have been reported. This study was conducted to investigate the effect of moderate-intensity endurance exercise on the detrimental effects of WTS on learning and spatial memory in rats. AIMS AND METHODS: Animals were divided into the Control group (CTL), the exercise group (Ex) which trained for 8 weeks, the WTS group (Wp) exposed to smoke inhalation (30 minutes per day, 5 days each week, and for 8 weeks), and the group that did exercise training and received waterpipe smoke together (Ex + Wp). Thereafter, learning and spatial memory were assessed by the Morris water maze test and hippocampal molecular measurements were done. RESULTS: Waterpipe smoke significantly impaired learning and spatial memory, decreased expression of neurotrophic factors IGF-1 and BDNF (p < .01 and p < .05 vs. CTL group, respectively), increased BAX to BCL-2 ratio (p < .001 vs. CTL group) in hippocampal tissue, and increased the percent of damaged neurons in the hippocampal CA1 area (p < .05 vs. CTL group). Combination of exercise training with WTS prevented learning and spatial memory disturbances and recovered expression of neurotrophic factors IGF-1 (p < .05 vs. Wp group), decreased BAX to BCL-2 ratio (p < .001 vs. Wp group), and reduced percentage of damaged neurons (p < .05 vs. Wp group). CONCLUSIONS: Findings suggest that moderate-intensity endurance exercise training can ameliorate learning and memory impairment caused by waterpipe smoke in rats. This effect partly results from increasing the expression of neurotrophic factors BDNF and IGF-1 and correcting pro/anti-apoptotic proteins balance in the hippocampal tissue. IMPLICATIONS: The popularity of WTS especially among youth is increasing. We assessed the effect of hookah smoke with/without exercise on learning and memory. Hookah smoke leads to CA1-neural injury and impairs learning and memory in rats. A combination of exercise training with hookah smoke attenuates these complications. This positive effect of exercise is partially mediated by the balancing of brain-derived neurotrophic factor (BDNF) and Insulin-like growth factor-1 (IGF-1) and also the BAX to BCL-2 ratio, a significant predictor of cell susceptibility to apoptosis. Extrapolation of these positive findings to humans needs complementary studies.

The landscape of exosomal non-coding RNAs in breast cancer drug resistance, focusing on underlying molecular mechanisms.

Breast cancer (BC) is the most common malignancy among women worldwide. Like many other cancers, BC therapy is challenging and sometimes frustrating. In spite of the various therapeutic modalities applied to treat the cancer, drug resistance, also known as, chemoresistance, is very common in almost all BCs. Undesirably, a breast tumor might be resistant to different curative approaches (e.g., chemo- and immunotherapy) at the same period of time. Exosomes, as double membrane-bound extracellular vesicles 1) secreted from different cell species, can considerably transfer cell products and components through the bloodstream. In this context, non-coding RNAs (ncRNAs), including miRNAs, long ncRNAs (lncRNAs), and circular RNAs (circRNAs), are a chief group of exosomal constituents with amazing abilities to regulate the underlying pathogenic mechanisms of BC, such as cell proliferation, angiogenesis, invasion, metastasis, migration, and particularly drug resistance. Thereby, exosomal ncRNAs can be considered potential mediators of BC progression and drug resistance. Moreover, as the corresponding exosomal ncRNAs circulate in the bloodstream and are found in different body fluids, they can serve as foremost prognostic/diagnostic biomarkers. The current study aims to comprehensively review the most recent findings on BC-related molecular mechanisms and signaling pathways affected by exosomal miRNAs, lncRNAs, and circRNAs, with a focus on drug resistance. Also, the potential of the same exosomal ncRNAs in the diagnosis and prognosis of BC will be discussed in detail.

An unusual site of a pericardial cyst in a child: A case report.

Pericardial cysts are rare congenital anomalies, often clinically silent and incidentally found on imaging. However, patients with pericardial cysts may present with chest pain, tachypnea, and, rarely, symptoms secondary to cardiac tamponade. Echocardiography (transthoracic or transesophageal) and chest computed tomography (CT) scan with contrast are diagnostic modalities of choice in patients with pericardial cysts. Conservative management is justified in asymptomatic patients, while a surgical approach is recommended in symptomatic patients. Here, we describe the case of a 12-year-old boy who underwent imaging during the coronavirus disease 2019 (COVID-19) pandemic and was incidentally found to have a pericardial cyst.

Effects of myo-inositol plus folic acid on ovarian morphology and oocyte quality in PCOS mouse model.

Although the role of myo-inositol (MYO) in promoting the oocyte quality of PCOS patients has been documented in human studies; the cellular effects of this supplement on oocytes have not been directly examined due to ethical limitations. In the first phase of this study, MYO dosimetry was carried out simultaneously with the PCOS model development. An effective dose was obtained following the assessment of fasting insulin and testosterone levels using ELISA and ovarian morphology appraisal by histopathology. In the second phase, following the continuous administration of the effective dose of MYO and dehydroepiandrosterone (DHEA), cellular evaluation was performed. The quality of oocytes from superovulation was analyzed by examining maturity and normal morphology percentage using a stereomicroscope, intracellular reactive oxygen species (ROS) and glutathione (GSH) levels using fluorometry, and ATP count evaluation using ELISA. The results revealed that, among the four different MYO concentrations, the 0.36 mg/g dose compared with the DHEA group reduced testosterone levels and large atretic antral follicles (LAtAnF) diameter. This dose also increased the corpus luteum count and the granulosa:theca (G/T)layer thickness ratio in antral follicles. Furthermore, this dose increased mature oocytes and normal morphology percentage, ATP count, and GSH levels; however, it decreased ROS levels in mature oocytes. Our findings provide the grounds for further cellular and molecular studies on the PCOS mouse model, suggesting that the improvement in mitochondrial function and its antioxidant properties is probably one of the mechanisms by which MYO increases oocyte quality.

Myrtenol Ameliorates Recognition Memories' Impairment and Anxiety-Like Behaviors Induced by Asthma by Mitigating Hippocampal Inflammation and Oxidative Stress in Rats.

INTRODUCTION: Asthma is related to neurochemical alterations which affect brain functions and lead to anxiety and cognitive dysfunctions. Myrtenol has sparked considerable interest due to its pharmacological effects, especially for the remediation of chronic disorders. Thus, the present research was designed to evaluate the impacts of myrtenol on anxiety-like behaviors, cognitive declines, inflammation, and oxidative stress in the hippocampus of asthmatic rats. METHODS: Rats were allocated to five groups: control, asthma, asthma/vehicle, asthma/myrtenol, and asthma/budesonide. Asthma was elicited in the rats by ovalbumin, and the animals were then exposed to myrtenol inhalation. Anxiety-like behavior and memory were assessed by elevated plus maze (EPM) and novel object and location recognition tests. Interleukins (interleukin-6, -17, and -10), tumor necrosis factor α (TNF-α), and oxidative stress biomarkers such as malondialdehyde (MDA), superoxide dismutase (SOD), Glutathione peroxidase (GPX), and total antioxidant capacity (TAC) in the hippocampus were assessed by the ELISA method. RESULTS: The levels of IL-6, IL-17, TNF-α, and MDA decreased, but GPX, SOD, and TAC levels increased in the hippocampus of asthmatic animals due to myrtenol inhalation. CONCLUSION: Myrtenol diminished asthma-induced anxiety-like behaviors and cognitive deficits in asthmatic rats; these effects might have been typically mediated by a reduction in inflammation and oxidative stress.

Association of ABCB1, ABCG2 drug transporter polymorphisms and smoking with disease risk and cytogenetic response to imatinib in chronic myeloid leukemia patients.

BACKGROUND: Despite acceptable results of imatinib in the treatment of chronic myeloid leukemia (CML), some patients fail to acquire a complete cytogenetic response (CCyR), which may be caused by polymorphisms in the pharmacogenetic genes. The study aimed to evaluate the association of two polymorphisms in the ABCB1 and ABCG2 genes with cytogenetic response to imatinib and the risk of CML development. METHODS: We genotyped ABCB1 (c .2677G/T/A) and ABCG2 (c .421C/A) polymorphisms by PCR-RFLP, T-ARMS-PCR methods in 111 patients with CML and 102 sex- and age-matched healthy subjects. CCyR was determined by standard chromosome banding analysis (CBA). RESULTS: Analysis of polymorphisms showed significant association of ABCG2 c.421CA genotype (p < 0.0001; OR = 0. 17), and ABCG2c.421A allele (p < 0.0001; OR = 0.31) with decreased risk of CML. Moreover, ABCB1c.2677GT- ABCG2c.421CC combined genotype (p = 0.017; OR = 4.20) was associated with increased risk of CML. Analysis of the joint effect of SNP-smoking combination showed that smoker subjects with the ABCB1c.2677GG/GT (p = 0.001; OR = 15.96, p = 0.001; OR = 8.13, respectively) or ABCG2c.421CC genotypes (p = 0.001; OR = 5.82) had the increased risk of CML, while the risk of the CML in non-smokers carrying the ABCG2c.421CA (p < 0.0001; OR = 0. 18) genotype was strongly decreased compared with reference group. Regarding drug response, ABCG2c.421 CC/CA genotypes in the smoker patients were associated with an increased risk of resistance to imatinib (p < 0.0001; OR = 7.02, p = 0.018; OR = 4.67, respectively). CONCLUSION: Our results suggest the impact of ABCG2c .421C/A polymorphism on CML development, and smoking may have a synergistic role in the risk of CML and resistance to imatinib.

Chemical composition of essential oil from female cones of Cupressus arizonica Greene.

The hydrodistilled volatile essential oils extracted from the female cones of Cupressus arizonica Greene that harvested in winter and spring seasons were analysed for their chemical composition by using gas chromatography-mass spectrometry (GC/MS). Twenty-four and seventeen components were identified, accounting for winter (95.5%) and spring (96.9%) of the total oils volume, respectively. Monoterpenoids (winter 93.7% and spring 95.0%) dominated the identified components in the essential oils, followed by a small portion of sesquiterpenoids (winter 1.8% and spring 1.9%). Monoterpene hydrocarbons (MH) (winter 90.9% and spring 94.9%) were the principal subclasses of components with α-pinene (winter 42% and spring 72%), ß-myrcene (winter 18.5% and spring 7.7%), δ-3-carene (winter 11.3% and spring 5.1%), limonene (9.4% for winter), and ß-pinene (5.3% for spring) as main constituents. Limonene (9.4%), camphor (0.2%), exo-methylcamphenilol (0.2%), terpinene-4-ol (0.6%), ß-citronellol (0.9%), and bornyl acetate (0.3%) were representative of the monoterpene hydrocarbon and oxygen-containing monoterpenoids (OM) in winter essential oil.

The effects of low-dose anthracycline-based chemotherapy on the levels of serum NT-proBNP level and left ventricular systolic and diastolic dysfunctions: A prospective observational study.

Background and Aims: The present study aimed to evaluate the relationship between serum N-terminal (NT)-pro-brain natriuretic peptide (BNP) levels and incidence of left ventricular (LV) systolic and diastolic dysfunction in patients who underwent low-dose anthracycline chemotherapy. Methods: This observational, prospective study was conducted on all patients with proven breast cancer, Hodgkin lymphoma, or non-Hodgkin lymphoma and no history of previous cardiac or any chronic diseases who were candidates for low-dose anthracycline chemotherapy from March 2017 to February 2018. We evaluated the serum NT-proBNP level and performed trans-thoracic echocardiography at baseline, 6, and 9 months after the chemotherapy. Results: Among 57 patients who successfully finished the study, 13 (22.8%) patients were men and 44 (77.19%) patients were women, and the total mean age was 52 ± 14.86 years. Our results revealed that the LV systolic and diastolic function and NT-proBNP mean levels were in the normal range at all three measured times. Additionally, no significant differences were observed between the levels of NT-proBNP, LV systolic, and diastolic function at baseline, 6, and 9 months after chemotherapy with low-dose anthracycline (p = 0.6, 0.1, and 0.4, respectively). Conclusion: Following low-dose anthracycline chemotherapy, none of our patients encountered LV systolic and diastolic dysfunctions and changes in serum NT-proBNP level. However, further studies with a larger population, longer follow-up duration, and higher dosage of anthracyclines are required to determine the effects of low-dose anthracycline on NT-proBNP level and LV systolic and diastolic functions.

Circular RNAs as prognostic and diagnostic biomarkers in renal cell carcinoma.

BACKGROUND: Circular RNAs (circRNAs) play pivotal roles in proliferation, apoptosis, migration, and invasion of renal cell carcinoma (RCC) cells. This study is aimed to systematically summarize the current evidence regarding the clinical implications of circRNAs in RCC patients. METHODS: A systematic search in PubMed, Embase, and Web of Science was performed until January 1, 2022. The correlation between the expression of circRNAs and clinicopathological, prognostic, and diagnostic features of RCC was evaluated using the meta-analysis. RESULTS: Ultimately, 41 studies with 3485 RCC patients were included in this study: 26 studies for clinicopathological features, 31 studies for prognosis, and eight studies for diagnosis. Altered expression of circRNAs was significantly associated with clinicopathological characteristics of RCC, including tumor size, tumor stage, lymph node metastasis, distant metastasis, and TNM stage. The tumor promoter circRNAs were associated with reduced overall survival (OS) (Hazard Ratio (HR) = 1.98, 95% confidence interval [CI] 1.68-2.34) and disease/progression/recurrence-free survival (DFS/PFS/RFS) (HR = 2.34, 95% CI 1.85-2.97). Contrarily, the tumor suppressor circRNAs were linked with better OS (HR = 0.49, 95% CI 0.40-0.60) and DFS/PFS/RFS (HR = 0.40, 95% CI 0.28-0.59). The pooled sensitivity and specificity of circRNAs for RCC diagnosis in tissue samples were both 0.84. These results in fluid samples (serum and urine) were 0.78 and 0.69, respectively. CONCLUSION: CircRNAs can serve as promising diagnostic and prognostic biomarkers for RCC.

The Role of the IL-33/ST2 Immune Pathway in Autoimmunity: New Insights and Perspectives.

Interleukin (IL)-33, a member of IL-1 cytokine family, is produced by various immune cells and acts as an alarm to alert the immune system after epithelial or endothelial cell damage during cell necrosis, infection, stress, and trauma. The biological functions of IL-33 largely depend on its ligation to the corresponding receptor, suppression of tumorigenicity 2 (ST2). The pathogenic roles of this cytokine have been implicated in several disorders, including allergic disease, cardiovascular disease, autoimmune disease, infectious disease, and cancers. However, alerted levels of IL-33 may result in either disease amelioration or progression. Genetic variations of IL33 gene may confer protective or susceptibility risk in the onset of autoimmune diseases. The purpose of this review is to discuss the involvement of IL-33 and ST2 in the pathogenesis of a variety of autoimmune disorders, such as autoimmune rheumatic, neurodegenerative, and endocrine diseases.

Assessment of burden of disease induced by exposure to heavy metals through drinking water at national and subnational levels in Iran, 2019.

The burden of disease attributable to exposure to heavy metals via drinking water in Iran (2019) was assessed at the national and regional levels. The non-carcinogenic risk, carcinogenic risk, and attributable burden of disease of heavy metals in drinking water were estimated in terms of hazard quotient (HQ), incremental lifetime cancer risk (ILCR), and disability-adjusted life year (DALY), respectively. The average drinking water concentrations of arsenic (As), cadmium (Cd), chromium (Cr), lead (Pb), mercury (Hg), and nickel (Ni) in Iran were determined to be 2.3, 0.4, 12.1, 2.5, 0.7, and 19.7 µg/L, respectively, which were much lower than the standard values. The total average HQs of heavy metals in drinking water in the entire country, rural, and urban communities were 0.48, 0.65 and 0.45, respectively. At the national level, the average ILCRs of heavy metal in the entire country were in the following order: 1.06 × 10-4 for As, 5.89 × 10-5 for Cd, 2.05 × 10-5 for Cr, and 3.76 × 10-7 for Pb. The cancer cases, deaths, death rate (per 100,000 people), DALYs, and DALY rate (per 100,000 people) attributed to exposure to heavy metals in drinking water at the national level were estimated to be 213 (95% uncertainty interval: 180 to 254), 87 (73-104), 0.11 (0.09-0.13), 4642 (3793-5489), and 5.81 (4.75-6.87), respectively. The contributions of exposure to As, Cd, Cr, and Pb in the attributable burden of disease were 14.7%, 65.7%, 19.3%, and 0.2%, respectively. The regional distribution of the total attributable DALY rate for all heavy metals was as follows: Region 5> Region 4> Region 1> Region 3> Region 2. The investigation and improvement of relatively high exceedance of As levels in drinking water from the standard value, especially in Regions 5 and 3 as well as biomonitoring of heavy metals throughout the country were recommended.

Synthesis, characterization, cytotoxicity and DNA/BSA binding of two amino acid palladium(II) complexes derived from alanine and valine.

Two novel palladium(II)-amino acid complexes, [Pd(Ala)2]·H2O (PA) and [Pd(Val)2].H2O (PV) (Ala = alanine; Val = valine) were synthesized and characterized through FTIR, UV/Vis, 1H-NMR spectroscopies, CHN analysis, X-ray crystallography and molar conductivity measurement. Furthermore, cytotoxicity of Pd(II) complexes against human leukemia cancer cell line, MOLT4 showed promising cancer cell death (CC50 = 0.71 ± 0.046 µM for PA; CC50 = 0.85 ± 0.063 µM for PV) that were less than cisplatin (1.59 ± 0.25 µM). Moreover, the interaction of both the complexes with DNA and BSA was studied using UV-Vis absorption and emission spectroscopic techniques that demonstrated the bindings occurred via van der Waals forces and hydrogen bond. Furthermore, the fluorescence titration showed that static quenching mechanism plays predominate role in binding process. All results showed that both complexes have more binding tendency to DNA in compared to BSA that can be a significant achievement for further medical purposes as a potential antitumor candidate. Finally, molecular docking simulation was performed for PA and PV complexes with DNA and BSA and demonstrated both complexes bind to the groove of DNA mainly by hydrogen bond and interact with site I of BSA via hydrogen bond as well.

CIRCULATING GHRELIN LEVELS AND SUSCEPTIBILITY TO COLORECTAL CÂNCER.

BACKGROUND AND OBJECTIVE: Considering the association between colorectal cancer (CRC) and both insulin resistance and obesity, and the prominent role of ghrelin in these metabolic disorders, we explored whether plasma levels of ghrelin were associated with CRC. Moreover, in the patients with CRC the possible correlations between ghrelin and insulin, insulin resistance, and body mass index (BMI) as an indicator of obesity were examined. METHODS: A total of 170 subjects, including 82 cases with CRC and 88 controls were enrolled in this study. Plasma levels of ghrelin, insulin, and glucose were measured in all the subjects using ELISA and glucose oxidase methods. Furthermore, insulin resistance was assessed by calculating HOMA-IR index. RESULTS: The cases with CRC had decreased ghrelin levels (P<0.001) and a higher HOMA-IR index (P<0.001) than controls. Interestingly, when CRC patients were stratified based on tumor site, lower ghrelin levels and a higher HOMA-IR index were observed in the patients with either colon or rectal cancer vs. controls too. Additionally, there were an age and BMI-independent negative correlation between ghrelin levels and HOMA-IR (r=-0.365, P<0.05), and an age-independent negative correlation between ghrelin levels and BMI (r=-0.335, P<0.05) in the rectal subgroup. CONCLUSION: Our findings support a role for ghrelin in connection with insulin resistance and obesity in CRC susceptibility; however, it needs to be corroborated by further studies.