Multi-epitope vaccine design against leishmaniasis using IFN-γ inducing epitopes from immunodominant gp46 and gp63 proteins.

There is no currently approved human vaccine against leishmaniasis. Utilization of immunogenic antigens and their epitopes capable of enhancing immune responses against leishmaniasis is a crucial step for rational in silico vaccine design. The objective of this study was to generate and evaluate a potential vaccine candidate against leishmaniasis, designed by immunodominant proteins from gp46 and gp63 of Leishmania major, which can stimulate helper T-lymphocytes (HTL) and cytotoxic T-lymphocytes (CTL). For this aim, the IFN-γ-inducing MHC-I and MHC-II binders were predicted for each examined protein (gp46 and gp63) and connected with appropriate linkers, along with an adjuvant (Mycobacterium tuberculosis L7/L12) and a histidine tag. The vaccine's stability, antigenicity, structure, and interaction with the TLR-4 receptor were evaluated in silico. The resulting chimeric vaccine was composed of 344 amino acids and had a molecular weight of 35.64 kDa. Physico-chemical properties indicated that it was thermotolerant, soluble, highly antigenic, and non-allergenic. Predictions of the secondary and tertiary structures were made, and further analyses confirmed that the vaccine construct could interact with the human TLR-4 receptor. Virtual immune simulation demonstrated strong stimulation of T-cell responses, particularly by an increase in IFN-γ, following vaccination. In summary, the in silico data indicated that the vaccine candidate showed high antigenicity in humans. It was also found to trigger significant levels of clearance mechanisms and other components of the cellular immune profile. Nevertheless, further wet experiments are required to properly assess the efficacy of this multi-epitope vaccine candidate against leishmaniasis.

In Silico Characterization of an Important Metacyclogenesis Marker in Leishmania donovani, HASPB1, as a Potential Vaccine Candidate.

Visceral leishmaniasis is a life-threatening infectious disease worldwide. Extensive experiments have been done to introduce potential vaccine candidates to combat leishmaniasis. The present study was done to evaluate Leishmania donovani hydrophilic acylated surface protein B1 as a potential vaccine candidate using in silico methods. For this aim, server-based predictions were performed regarding physicochemical characteristics, solubility, antigenicity, allergenicity, signal peptide, transmembrane domain, and posttranslational modifications (PTMs). Also, secondary and tertiary structures were predicted using NetSurfP-3.0 and I-TASSER, respectively. The 3D model was further subjected to refinement and validation, and promising B-cell, cytotoxic T-lymphocyte (CTL; human, dog), and helper T-lymphocyte (HTL; human) epitopes were predicted. The protein had a molecular weight of 42.19 kDa, with high solubility (0.749), stability (instability index: 21.34), and hydrophilicity (GRAVY: -2.322). No signal peptide or transmembrane domain was predicted, and the most abundant PTMs were phosphorylation, O-glycosylation, and acetylation. Many coils and disordered regions existed in the secondary structure analysis, and the tertiary model had a good confidence score (-0.79). Next, the ProSA-web and PROCHECK tools showed adequate improvements in the refined model compared to the crude model. Only 4 shared B-cell epitopes among three web servers (ABCpred, BepiPred 2.0, and SVMTriP) were shown to be antigenic, nonallergenic, and with good water solubility. Also, five potent CTL epitopes in dogs and five in humans were predicted. Notably, two HTL epitopes were found to be potential IFN-γ inducers. In conclusion, our results demonstrated several immunogenic epitopes in this protein, which could be directed towards multiepitope vaccine design.

Resistance training, gremlin 1 and macrophage migration inhibitory factor in obese men: a randomised trial.

OBJECTIVE: This study aimed to determine how different resistance training protocols affect gremlin 1, macrophage migration inhibitory factor (MIF), cardiometabolic, and anthropometric measures in obese men. METHODS: Forty-four males with obesity (weight: 93.2 ± 2.2 kg, BMI: 32.9 ± 1.2 kg/m2, age: 27.5 ± 9.4 years) were randomly assigned to traditional resistance training (TRT, n = 11), circuit resistance training (CRT, n = 11), interval resistance training (IRT, n = 11) or control (C, n = 11) groups. TRT group performed ten exercises at 50% of 1RM with 14 repetitions for three sets and 30 seconds rest interval between exercises and 1.5 min rest between sets, the CRT protocol included three circuits of 10 exercises, at an intensity of 50% of 1-RM, 14 repetitions with a minimum rest (< 15 s) between exercises and 3 min rest between sets, and the IRT group performed two sets of the same exercises with 50% of 1 RM, and 14 repetitions were followed with active rest of 25% of 1RM and 14 repetitions. All resistance training groups performed 60 min per session resistance exercises, 3 days per week, for 12 weeks. Measurements were taken at baseline and after 12 weeks of exercise training. RESULTS: Resistance training (TRT, CRT, and IRT) significantly decreased plasma levels of gremlin (TRT from 231.0 ± 5.8 to 210.0 ± 11.6 ng/ml, CRT from 226.0 ± 7.6 to 188.0 ± 7.7 ng/ml and, IRT from 227.0 ± 6.3 to 183.0 ± 9.0 ng/ml, effect size (ES): 0.50), MIF (TRT from 251.0 ± 7.4 to 260.0 ± 6.5 ng/ml, CRT from 248.0 ± 10.9 to 214.0 ± 9.0 ng/ml and, IRT from 247.0 ± 8.9 to 196.0 ± 6.9 ng/ml, ES: 0.55) and CRP (TRT from 28.4 ± 1.7 to 23.3 ± 2.1 nmol/l, CRT from 28.5 ± 2.2 to 21.1 ± 1.8 nmol/l, IRT from 28.1 ± 1.3 to 20.8 ± 1.3 nmol/l, ES: 0.49) compared to the control group (p < .05), but these reduction were greater in the CRT and IRT groups compared to the TRT group (p < .05). CONCLUSION: The CRT and IRT protocols had more beneficial improvement in gremlin 1, MIF, body composition, and cardiometabolic risk factors compared to the beneficial changes produced by TRT protocol.

Intensity Dependent Effects of Interval Resistance Training on Myokines and Cardiovascular Risk Factors in Males With Obesity.

Objective: To determine the effects of different intensities of interval resistance training (IRT) protocols on the levels of select myokines (decorin, follistatin, myostatin, activin A, transforming growth factor beta-1 [TGF-ß1]), and cardiometabolic and anthropometric measures in males with obesity. Methods: Forty-four obese males (age: 27.5 ± 9.4 yr.; height: 165.4 ± 2.8 cm; weight: 97.9 ± 2.6 kg and BMI: 35.7 ± 4.3 kg/m2) were randomly assigned to one of four groups (n=11 per group): low-intensity interval resistance training (LIIRT), moderate-intensity interval resistance training (MIIRT), high-intensity interval resistance training (HIIRT) or control (C). The LIIRT group performed 10 exercises in 3 sets of 40% (20 repetitions), the MIIRT group performed 10 exercises in three sets of 60% (13 repetitions), and the HIIRT group performed 10 exercises in three sets of 80% (10 repetitions) of one maximum repetition (1RM), which were followed with active rest of 20% of 1RM and 15 repetitions. The resistance training groups exercised ~70 min per session, 3 days per week, for 12 weeks. Measurements were taken at baseline and after 12 weeks of exercise training. Results: Baseline levels of myokines, cardiovascular risk factors, anthropometry, body composition, and cardio-respiratory fitness were not different between the four groups (p>0.05). The group x time interactions for decorin, activin A, follistatin, myostatin, and TGF-ß1, total cholesterol (TC), triglyceride (TG), high-density cholesterol (HDL), low-density cholesterol (LDL), anthropometry, body composition, and cardio-respiratory fitness were statistically significant (p<0.05). There were increases in post-test values for decorin, follistatin, HDL (p<0.05) and decreases in TC, TG, TGF-ß1, LDL, and myostatin levels in the LIIRT, MIIRT, and HIIRT groups compared to pretest values (p<0.05). Changes in fat mass, VO2peak, HDL, TG, glucose, activin A, decorin were not significant in LIIRT compared to the control group, while changes in activin A, follistatin, and TFG-ß1 levels were greater in HIIRT and MIIRT groups compared to the LIIRT group (p<0.05). Conclusion: The LIIRT, MIIRT, and HIIRT protocols all produced beneficial changes in decorin, activin A, follistatin, myostatin, and TGF-ß1 levels, and cardiometabolic risk factors, with greater effects from the MIIRT and HIIRT protocols compared to LIIRT.

Promising effects of parasite-derived compounds on tumor regression: a systematic review of in vitro and in vivo studies.

The parasites are repeatedly confronting their host to take advantage of nutrients for multiplication and survival. In this sense, a wide spectrum of molecules is released from both sides, with immune-regulatory activity, accompanying this biological battle. Such parasites and their valuable molecules can be directed toward microbial-based cancer therapy. Herein, we contrived a systematic review to gather information on the antitumor activity of parasite-derived compounds. Following systematic search in Web of Science, ScienceDirect, Scopus, PubMed, ProQuest and Embase until 31 December 2019, a total number of 51 articles (54 datasets) were finally included in this review. Thirteen parasitic agents were found to possess possible antitumor activity, comprising protozoan species Toxoplasma gondii, Trypanosoma cruzi, Trichomonas vaginalis, Acanthamoeba castellanii, Besnoitia jellisoni, Leishmania major, Plasmodium yoelii, and Plasmodium lophurae, as well as parasitic helminths Toxocara canis, Echinococcus granulosus, Taenia crassiceps, Trichinella spiralis, and Schistosoma mansoni. Most experiments were done based on antigenic preparations from T. gondii (16 studies), E. granulosus (10 studies), T. spiralis (8 studies), and T. cruzi (6 studies). Possible antitumor properties of the selected parasites were revealed in this review. However, precise molecular basis of anticancer activity for each parasite remains to be elucidated in the future.

Ethnobotanical Survey of Medicinal Plants used to Treat Cardiovascular Disorders in Ghasemloo Valley of Urmia City.

AIMS: Many pharmaceutical plants belonging to this region are used as the traditional drug by traditional physicians of the Urmia city in order to treat signs of disorders and cardiovascular system diseases. BACKGROUND: The Ghasemloo valley located in Urmia city is one of the typical areas in northwestern Iran and includes many pharmaceutical and plant species. OBJECTIVE: Many pharmaceutical plants belonging to this region are used as the traditional drug by traditional physicians of the Urmia city in order to treat several symptoms of disorders and cardiovascular system diseases. METHOD: A study was performed among 35 grocers in Urmia city to identify effective and famous pharmaceutical plants in the treatment of cardiovascular and related diseases. Firstly, a complete list of Urmia grocers was prepared by the Food and Drug Administrator of the Urmia University of Medical Sciences. The direct observation and interview, alongside collecting herbarium samples of usual and effective indigenous medicinal plants, were used to identify disorders and different signs of cardiovascular diseases. Questionnaires included personal information of grocers, and completed indigenous plants list containing information, including the plant's local name, the used organ, method of use, and the traditional therapeutic effect. Herbarium samples mentioned in the questionnaire were collected from the region and sent to the Jahad-e-Keshavarzi Research Centers and the Agriculture Faculty of Urmia university to determine the genus and species. After identifying and confirming the plant species, data related to the plant and results of cardiovascular research conducted on them were collected and recorded with reference to valid scientific sites. Data were entered into the Excel 2010 program and then analyzed. RESULT: 60 medicinal plants of 26 families in Urmia were identified as effective in the treatment of cardiovascular diseases from interviews and questionnaires; some plants mentioned in this study had known traditional therapeutic effects on cardiovascular disorders in the literature and some were identified with new effects. Results showed that the most therapeutic effects in cardiovascular diseases belonged to families Rosaceae (15%), Fabaceae (13%), Asteraceae (13%), and Apiaceae (10%). The most used organs of plants were the leave (23%) and fruit (19%). Plants were used mainly as an infusion (68%) in the traditional method. Most plants of this study were used to treat the blood cholesterol (29%), hypertension (9%), blood coagulation, prevention of bleeding (9%), and decrease in abdominal fat (9%). CONCLUSION: Some herbs introduced in this study have new therapeutic effects introduced for the first time. It is necessary to study the therapeutic effects of indigenous plants presented in this research in order to prove studied and mentioned therapeutic effects and provide a study field for researchers in relation to identifying effective substances and studying claimed clinical effects of these plants on different cardiovascular diseases.

Systematic review on telemedicine platforms in lockdown periods: Lessons learned from the COVID-19 pandemic.

With the onset of the coronavirus disease 2019 (COVID-19) outbreak, the transformation of the care delivery model from conventional in-person (face to face) to largely virtual or remote care has been accelerated to appropriately allocate resources and constrain the spread of the virus. In this regard, telemedicine is a breakthrough technology to battle against the COVID-19 emergency. Therefore, we sought to identify the telemedicine applications in the COVID-19 pandemic (tele-COVID) according to interaction modes, transmission modalities, and disease categories. This systematic review was conducted through searching five databases including PubMed, Scopus, ProQuest, Web of Science, and Science Direct. Inclusion criteria were studies clearly outlining any use of telemedicine interactive mode during the COVID-19 pandemic, written in English language and published in peer-reviewed journals in 2020. Finally, 43 articles met the inclusion out of the 1118 search results. Telemedicine provides a diversity of interaction modes and modalities affordable by patients and physicians including short message service, E-mail and web portals, secure telephone calls or VOIP, video calls, interactive mobile health applications (m-Health), remote patient monitoring, and video conferencing. Transmission of video data using synchronized video calls via common social media had the highest and exchange of data using store-forward service via secure messaging technology and prerecorded multimedia had the lowest popularity for virtual disease management during the COVID-19 outbreak. Selection of telemedicine communication services and interaction modes with regard to its use-case, disease category, and application plays a significant role in the success of remote disease management infrastructures in this scenario and their implication for a better future healthcare system.

A systematic review and meta-analysis of recent studies reporting hormone levels related to thyroid gland function in migraineurs, until April 2020.

PURPOSE: The purpose of the current study was to evaluate thyroid function in terms of serum thyroid-stimulating hormone (TSH, also known as thyrotropin), 3,5,3'-triiodo-L-thyronine (T3), and 3,5,3',5'-tetraiodo-L-thyronine (T4, also known as thyroxine) levels in migraineurs in comparison with non-migraineurs using a systematic review of literature and a meta-analysis. METHODS: This is a systematic review of case-control studies on serum TSH, T3, and T4 concentrations of migraineurs in comparison with non-migraineurs. After extracting the data from the finally included studies, the weighted overall standardized mean difference (SMD) was calculated. RESULTS: The weighted overall SMD for the impact of TSH, T3, and T4 blood levels for migraineurs in comparison with non-migraineurs was as follows: 0.804 (95% CI, 0.045-1.564), - 0.267 (95% CI, - 0.660-0.125), 0.093 (95% CI, - 0.077-0.263), respectively. It is noteworthy that only the p value for the significance of the overall SMD for serum TSH level was statistically significant (p = 0.038), as examined by the z-test. CONCLUSIONS: The results of the current study point to an association between migraine pathogenesis and changing TSH levels in comparison with those of controls.

Serum vascular endothelial growth factor (VEGF) levels in ischemic stroke patients: a systematic review and meta-analysis of case-control studies.

Serum VEGF level is regarded to be a biomarker for the diagnosis of stroke. Even though there have been published plethora of original articles describing higher blood VEGF concentrations since the 1970s, however, there is no any meta-analysis report for serum VEGF levels in the field of evidence-based medicine yet. A systematic review was performed by searching the online biomedical databases including retrieving 14 case-control studies including within-article subgroups after fulfilling the inclusion and exclusion criteria without the beginning date restriction, until 2020 for ischemic stroke patients. The Q quantity and I2% statistic index showed a high heterogeneity (84.895 and 84.687, respectively) and the random-effects model of meta-analysis was applied for further analyses. The meta-analysis on a total number of 769 stroke subjects and 621 controls found that the weighted pooled SMD for overall serum VEGF levels on different days of testing was 1.92 (95% CI, - 4.059-0.219, p value = 0.079) and the pooled SMD for overall serum VEGF levels on day 1 of testing was - 1.083 (95% CI, - 4.229-2.063, p value = 0.500). The meta-regression results demonstrated that different days of testing do not significantly affect serum VEGF concentrations in ischemic patients and actually their serum levels are time-independent. Based on the recently published studies, this meta-analysis showed that serum VEGF levels were not significantly associated with an ischemic stroke diagnosis. Thus, researchers may concern another ideal serum or cerebrospinal fluid-derived biomarker for stroke diagnosis.

Aberrant Expression of Peroxisome Proliferator-Activated Receptors in Colorectal Cancer and Their Association with Cancer Progression and Prognosis.

INTRODUCTION: Peroxisome proliferator-activated receptors (PPARs), PPARα, PPARγ, and PPARδ, are nuclear ligand-activated transcription factors which presumably contribute to a broad range of pathophysiological processes, such as tumorigenesis. Nevertheless, their exact role as tumor suppressors or promoters is not straightforward in colorectal cancer (CRC). Therefore, expression values of these PPARs and their relation with tumor progression and prognosis were examined in CRC patients. METHODS: In this work, the relative expression values of the PPARs were measured by real-time polymerase chain reaction in 100 CRC tumor tissues paired with adjacent normal tissues. After that, the association between relative expression values of the PPARs in tumor tissues and the cancer progression-related clinicopathological characteristics as well as overall survival of patients were assessed. RESULTS: While PPARα and PPARδ seemed to be overexpressed, PPARγ was suppressed in CRC tumor tissues compared with paired adjacent normal tissues (p = 0.0001). The relative expressions of PPARα and PPARδ were negatively associated with tumor size, tumor grade, TNM stage, metastasis, lymphatic invasion, and decreased overall survival time (p < 0.05). The same associations, but in reverse direction, were found for PPARγ. CONCLUSIONS: It was found that PPARα and PPARδ were overexpressed while PPARγ was suppressed in CRC tumor tissues, and these deregulations are associated with cancer progression and poor prognosis.

Efficiency of Nebulizing Furosemide in the Treatment of Chronic Pulmonary Obstructive Disease: A Systematic Review and Meta-Analysis of Clinical Trials.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is one of the most common chronic illnesses in humans. Among both oral and intravenous diuretics, nebulizing furosemide (Lasix) is the most commonly used agent. The purpose of this study was to ascertain the therapeutic effects of nebulizing furosemide compared with placebo in the treatment of COPD using a systematic review and meta-analysis of clinical trials. MATERIALS AND METHODS: This review was performed based on the preferred reporting items for systematic reviews and meta-analyses (PRISMA) protocol. The databases of Web of Science, Google Scholar, PubMed, and Scopus were independently searched by two researchers using MeSH keywords. Studies published between 2002 and 2018 in different parts of the world were considered. The meta-analysis was performed through STATA 14 software and the heterogeneity was assessed using Q statistic or I2 index. RESULTS: From 40 selected articles, 8 articles were finally included in the systematic review process. The analyses were performed considering two groups; nebulizing furosemide treatment (i.e. case) and placebo (i.e. control). Based on the forest plots, the average values of PaCO2 were 48.3 (39.04-57.56) and 46.56 (39.94-53.18) in the case and control groups, respectively. Also, the mean forced expiratory volume in the first second (FEV1) was 49 (31.32-66.67) and 46.87 (31.44-62.30) in the case and control groups, respectively. Meta-regression analysis showed that both heart and pulse rates in the nebulizing furosemide group decreased by increasing the year of study and sample size (P <0.001). The heterogeneity among the studies was found to be 72.2%, which is classified as severe heterogeneity. CONCLUSION: nebulizing furosemide can improve and normalize the vital signs and other respiratory variables in patients with COPD.

Association of High Expression Levels of SOX2, NANOG, and OCT4 in Gastric Cancer Tumor Tissues with Progression and Poor Prognosis.

BACKGROUND: Expression of the essential regulator genes, SOX2, NANOG, and OCT4, so-called as stemness factors, is prerequisite for the tumorigenic capability of cancer stem cells (CSCs) and their potential role in the formation and progression of various human cancers. METHODS: In this study, the expression levels of SOX2, NANOG, and OCT4 were quantified by a qRT-PCR method in 100 gastric cancer tumor tissues vs the paired adjacent normal tissues. Then, the relationship between the expression of the three genes in gastric cancer tumor tissues and the clinicopathological characteristics and overall survival of patients was investigated. RESULTS: Higher expression levels of SOX2, NANOG, and OCT4 were found in gastric cancer tumor tissues compared with those in paired adjacent normal tissues (P = 0.0001). Overexpression of the mentioned genes in gastric cancer tumor tissues was resolved to be significantly associated with tumor size (P < 0.05), TNM stage (P = 0.001), tumor grade (P < 0.01), and shortened overall survival time (P = 0.0001). CONCLUSIONS: These findings indicted that the stemness factors SOX2, NANOG, and OCT4 are significantly overexpressed in gastric cancer and may serve as potential biomarkers of gastric cancer progression and prognosis.

Molecular Dynamics Mechanisms of the Inhibitory Effects of Abemaciclib, Hymenialdisine, and Indirubin on CDK-6.

BACKGROUND: Cyclin-Dependent Kinases-6 (CDK-6) is a serine/threonine protein kinase with regular activity in the cell cycle. Some inhibitors, such as abemaciclib, hymenialdisine, and indirubin, cause cell arrest by decreasing its activity. OBJECTIVES: The purpose of this study was to evaluate the Molecular Dynamic (MD) effects of abemaciclib, hymenialdisine, and indirubin on the structure of CDK-6. METHODS: The PDB file of CDK-6 was obtained from the Protein Data Bank (http://www.rcsb.org). After the simulation of CDK-6 in the Gromacs software, 200 stages of molecular docking were run on CDK-6 in the presence of the inhibitors using AutoDock 4.2. The simulation of CDK-6 in the presence of inhibitors was performed after docking. RESULTS: Abemaciclib showed the greatest tendency to bind CDK-6 via binding 16 residues in the binding site with hydrogen bonds and hydrophobic bonding. CDK-6 docked to hymenialdisine and indirubin increased the Total Energy (TE) and decreased the radius of gyration (Rg). CDK-6 docked to hymenialdisine significantly decreased the coil secondary structure. CONCLUSION: CDK-6 is inhibited via high binding affinity to abemaciclib, hymenialdisine, and indirubin inhibitors and induces variation in the secondary structure and Rg in the CDK-6 docked to the three inhibitors. It seems that developing a drug with a binding tendency to CDK6 that is similar to those of abemaciclib, indirubin, and hymenialdisine can change the secondary structure of CDK6, possibly more potently, and can be used to develop anticancer drugs. However, additional studies are needed to confirm this argument.

Cancer stem cells and nanotechnological approaches for eradication.

Cancer stem cells (CSCs) are currently known as the main cause of tumor recurrence. After chemotherapy is completed, CSCs proliferate and then differentiate to generate new tumor tissues. Similar to normal stem cells, this non-uniformly distributed cell population in the tumor tissue has self-renewal capacity and is responsible for survival of the tumor and difference in its genetic and metabolic characteristics. Followed by gene instability in CSCs, new phenotypic markers are aberrantly expressed in CSCs subpopulation. Hence, some of the surface markers and metabolic pathways that are upregulated in CSCs may be applied as specific targets for development of diagnostic and therapeutic approaches. In this review article, the distinctive properties of CSCs including signal pathways implicated in self-renewal and surface markers were discussed. Moreover, targeting CSCs based on their specific properties using nanodrugs was reviewed.

Independent and Combined Effects of Antioxidant Supplementation and Circuit Resistance Training on Selected Adipokines in Postmenopausal Women.

We examined the effects of the independent and combined effects of Zataria Multiflora supplementation and circuit resistance training (CRT) on selected adipokines among postmenopausal women. Forty-eight postmenopausal women were divided into four groups: Exercise (EG, n = 12), Zataria Multiflora (ZMG, n = 12), exercise and Zataria Multiflora (ZMEG, n = 12), and control (CG, n = 12). Participants in experimental groups either performed CRT (3 sessions per week with intensity at 55% of one-repetition maximum) or supplemented with Zataria Multiflora (500 mg every day after breakfast with 100 ml of water), or their combination, for 8 weeks. Blood samples were collected at pre- and post-intervention for measuring selected adipokines, including visfatin, omentin-1, vaspin, FGF-21, adiponectin, leptin, and ghrelin. Our findings demonstrated that visfatin, vaspin, and leptin levels significantly decreased over the intervention period (all p < 0.05), with these values were lower in EG and ZMEG in comparison to CG at post-intervention (all p < 0.05). Visfatin and vaspin levels were also lower in ZMEG in comparison to EG at post-intervention (both p < 0.05). In contrast, omentin-1, ghrelin, adiponectin, and FGF21 significantly increased in EG and EMG (all p < 0.05) after CRT. These findings suggest that Zataria Multiflora supplementation by itself has little effect on measured adipokines; however, its combination with CRT produced noticeable effects on circulating levels of these adipokines, even more than CRT alone. Consequently, a combination of CRT and Zataria Multiflora supplementation may represent a potentially beneficial non-pharmacologic intervention on some selected adipokines in postmenopausal women.

Analgesic Medicinal Plants in Shahrekord, Southwest of Iran: An Ethnobotanical Study.

BACKGROUND: Identification of indigenous medicinal plants, including the gathering of information regarding the uses of these plants can help find out their traditional pharmacological activities and their benefits for the community's healthcare system. In this study, an ethnobotanical investigation was conducted in Shahrekord city, southwest of Iran to indicate the ethnobotanical knowledge about analgesic medicinal plants in the region and the methods of using them. MATERIALS AND METHODS: To this end, plant antioxidants and analgesic medicinal plants were identified. For this purpose, a questionnaire was used to obtain indigenous knowledge from traditional therapists in Shahrekord regarding pain relief using medicinal plants. This ethnobotanical study was conducted in 2018 with the participation of 29 traditional therapists of the region under purpose. Finally, the data drawn from the questionnaires were analyzed using the Excel software. The frequency of plants use was also calculated. RESULTS: Our study showed that in Shahrekord, 23 species of medicinal plants are used to relieve pain. The highest frequency of use was obtained for Eugenia caryophylata (44%), followed by Alhagi maurorum (31%), Tribulus terrestris (27%), and angustifolia (24%). The Laminaceae family (7 species) was the most frequently used plant family for pain relief. The most frequently used plant organ to relieve the pain was flower (25%), followed by the stem (22%) and leaves (19%). CONCLUSION: Given the high importance of medicinal plants in Shahrekord, the results of this study and additional scientific investigations can help produce more effective and less harmful drugs from medicinal plants.

Contribution of Blastocystishominis subtypes and associated inflammatory factors in development of irritable bowel syndrome.

Blastocystis hominis with worldwide distribution is a human intestinal protozoa found in all countries. There have been differences in the severity of the pathogenesis of various Blastocystis spp. and a concomitant variation in the plasma concentration of the cytokines in patients with irritable bowel syndrome. In the present study, we aimed to demonstrate the contribution of B. hominis subtypes in the development of irritable bowel syndrome. Stool samples were collected from patients with gastrointestinal disorders. All samples were evaluated through native-lugol method. Total DNA was extracted. A PCR protocol was developed to amplify a specific region of the SSU ribosomal DNA (rDNA) gene. Serum levels of IL-6 and TNF-α were determined by immunoassay methods. The ClustalW algorithm was applied to align and blast the nucleotide sequences of the amplified region of the SSU rDNA gene. To evaluate the phylogenetic and molecular evolutionary of the nucleotide sequences, we used the MEGA software. In this study, we found 26 haplotypes of B. hominis in the studied samples which were collectively belong to five subtypes (ST1, ST2 in patients without irritable bowel syndrome vs. ST3 and two unknown subtypes in patients with irritable bowel syndrome). Result of ELISA showed a high level of IL-6 and TNF-α in the serum of patients with irritable bowel syndrome. The genetic heterogeneity of B. hominis and the existence of different subtypes of the protozoan in patients with IBS may shed light to the fact that some subtypes of parasites may involve in the pathogenesis of IBS.

Circulating levels of the miRNAs, miR-194, and miR-29b, as clinically useful biomarkers for colorectal cancer.

The microRNAs (miRNAs), miR-194 and miR-29b, have been shown to downregulate in colorectal cancer (CRC) and may identify and classify CRC patients as compared with those in control subjects. In the current study, we aimed to explore whether the serum levels of the miRNAs could be potential biomarkers for diagnosis and prognosis of CRC. A quantitative reverse-transcription polymerase chain reaction (qRT-PCR) assay was utilized to determine and compare serum levels of miR-194 and miR-29b in 55 patients with CRC and 55 control subjects. The correlations between levels of the miRNAs and clinicopathological stages of cancer were analyzed in patients. Receiver operating characteristic (ROC) curve and survival analyses were carried out, respectively, to determine diagnostic and prognostic values of the miRNAs. Serum levels of miR-194 and miR-29b were found to be significantly lower in CRC patients than those in control subjects (P < 0.0001). Moreover, serum levels of the miRNAs in patients were inversely correlated with the advanced TNM stages (P = 0.01). ROC curve and survival analyses revealed that reduced levels of the miRNAs could serve as diagnostic and prognostic biomarkers for patients with CRC (P = 0.0001). Serum levels of miR-194 and miR-29b may serve as potential biomarkers for diagnosis and prognosis of CRC.

Association between adipokine and myeloperoxidase levels in patients with coronary artery disease.

The adipokines, leptin and adiponectin, have a prominent role in the pathogenesis of coronary artery disease (CAD). The inflammatory enzyme, myeloperoxidase (MPO) also has an important role in the pathogenesis of CAD. Association of the adipokines with MPO remains to be resolved in patients with CAD. In this case-control study, 100 patients with CAD and 100 control subjects were appropriately recruited. Angiographic evaluation assigned the presence of CAD. Plasma leptin, adiponectin and MPO concentrations were measured using immunoassay methods. Other conventional cardiovascular risk factors were also recorded. Leptin and MPO concentrations were significantly increased in CAD patients compared to control subjects (25.38 ± 5.91 ng/ml vs. 3.68 ± 1.95 ng/mL and 52.85 ± 12.90 ng/mL vs.  23.00 ± 3.60 ng/mL, P=0.001, respectively). In contrast, adiponectin was significantly decreased in CAD patients compared to control subjects (5.62 ± 1.15 µg/mL vs. 9.25 ± 1.8, P = 0.001). There was a strong positive association between leptin and MPO concentrations only in CAD patients (P = 0.01). In contrast, a significant inverse association was found between adiponectin and MPO concentrations in CAD patients (P = 0.01). The associations also were significant after adjustment for other conventional risk factors (P = 0.001). Considering the presence of significant association between leptin and MPO, as well as adiponectin and MPO in patients with CAD, it may be inferred that the contribution of the adipokines in the pathogenesis of CAD may be, in part, through affecting the MPO concentration.

Elevated level of microRNA-21 in the serum of patients with colorectal cancer.

In patients with colorectal cancer, circulating micro RNA-21 (miR-21) is overexpressed and may act as a potential diagnostic and prognostic biomarker. In the present study, serum miR-21 level was determined in patients with colorectal cancer and control subjects in an attempt to explore its potential clinical diagnostic and prognostic value. Serum levels of miR-21 were measured in 40 patients with colorectal adenocarcinoma and 40 control subjects using a quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) assay. Serum miR-21 levels were compared in the colorectal cancer patients and control subjects. Furthermore, the association between serum miR-21 level and the clinical stages of tumors was also examined in the patients. Serum miR-21 level was significantly elevated in colorectal adenocarcinoma patients relative to control subjects (P=0.0001), and it was revealed as a potential diagnostic biomarker for differentiating the patients from control subjects. Increased levels of serum miR-21 were associated with clinical stages of tumors in the patients (P=0.01). These results indicated that serum miR-21 levels could serve as a reliable diagnostic and prognostic biomarker for colorectal adenocarcinoma.