The association between energy-adjusted dietary inflammatory index and metabolic syndrome and its mediatory role for cardiometabolic diseases: a prospective cohort study.

Background: Metabolic syndrome (MetS) is a collection of medical conditions that elevate the chance of cardiovascular disease. An unhealthy diet is a major risk factors for MetS through different mechanisms, especially systemic chronic inflammation. Objective: This study aimed to investigate the effect of dietary inflammatory potential on MetS incidence and the role of MetS in the association between Energy-adjusted dietary inflammatory index (E-DII) and cardiometabolic diseases. Methods: In this prospective cohort study, 10,138 participants were recruited. All participants were divided into MetS or non-MetS groups based on the Adult Treatment Panel III criteria. The E-DII was used to assess the inflammatory potential of diet. After excluding the participants with MetS at baseline, 2252 individuals were followed for 5 years (longitudinal phase), and the effect of E-DII on MetS incidence was investigated using logistic regression models (p-value <0.05). Results: The cohort's mean age (45.1% men) was 48.6 ± 10.0 years. E-DII ranged from -6.5 to 5.6 (mean: -0.278 ± 2.07). Higher E-DII score had a 29% (95%CI: 1.22-1.36) increased risk for incidence of MetS and its components during five-year follow-up. Also, E-DII was significantly associated with the prevalence of MetS (OR = 1.55, 95%CI: 1.51-1.59). Among MetS components, E-DII had the strongest association with waist circumference in the cross-sectional study (OR = 2.17, 95%CI: 2.08-2.25) and triglyceride in the longitudinal study (OR = 1.19, 95%CI: 1.13-1.25). The association between E-DII and MetS was consistent in both obese (OR = 1.13, 95%CI:1.05-1.21) and non-obese (OR = 1.42, 95%CI: 1.27-1.60) individuals and stronger among non-obese participants. Additionally, MetS mediated the association between E-DII and hypertension, diabetes, and myocardial infarction. Conclusion: In conclusion, a pro-inflammatory diet consumption is associated with a higher risk of MetS and its components. Furthermore, a pro-inflammatory diet increases the risk of cardiometabolic diseases. The higher E-DII had a stronger association with MetS, even among normal-weight individuals.

The association between energy-adjusted dietary inflammatory index and 10-year cardiovascular risk: Fasa adult cohort study.

A healthy diet is dominant in cardiovascular disease (CVD) prevention. Inflammation is pivotal for CVD development. This study aimed to evaluate the association between the pro-inflammatory diet and the CVD risk. This cross-sectional study involved 10,138 Fasa adult cohort study participants. After excluding participants with missing data, the Energy-Adjusted Dietary Inflammatory Index (E-DII) was calculated to assess the inflammatory potential of diet using the recorded Food Frequency Questionnaire. Framingham risk score (FRS) was used to predict the 10-year risk of CVD. The association between E-DII and high risk for CVD was investigated using multinominal regression. After exclusion, the mean age of studied individuals (n = 10,030) was 48.6 ± 9.6 years, including 4522 men. Most participants were low risk (FRS <10%) for CVD (87.6%), while 2.7% of them were high risk (FRS ≥20%). The median FRS was 2.80 (1.70, 6.30). The E-DII ranged from -4.22 to 4.49 (mean E-DII = 0.880 ± 1.127). E-DII was significantly associated with FRS. This result persisted after adjusting for confounding factors and in both genders. This study revealed that the pro-inflammatory diet significantly increases the CVD risk. Consequently, reducing the inflammatory potential of diet should be considered an effective dietary intervention in CVD prevention.

Association between TMPRSS2 rs2070788 polymorphism and COVID-19 severity: a case-control study in multiple cities of Iran.

Introduction: Host genetic variations have been identified as potential influencers of COVID-19 infection. This study aimed to examine the association between transmembrane serine protease type 2 (TMPRSS2) rs2070788 single nucleotide polymorphism (SNP) and the prognosis of COVID-19 in Iranian populations. Method: This case-control study was performed on 756 COVID-19 patients and 59 healthy individuals across Iran. Clinical data, blood samples, and the presence of the TMPRSS2 rs2070788: G>A SNP were determined using T-ARMS-PCR. Additionally, serum levels of tumor necrosis factor α (TNF-α), C-reactive protein (CRP), interleukin-6 (IL-6), and IL-1ß were evaluated in the collected blood samples. Results: No significant association was found between the genotypes and allele frequencies of TMPRSS2 rs2070788 SNP and susceptibility to or mortality from COVID-19 infection. However, we observed a substantial increase in IL-6 and CRP levels associated with the severity of COVID-19, while no such trend was observed for IL-1ß and TNF-α. This study showed a considerable rise in TNF-α and IL-1ß serum levels exclusively in COVID-19 patients with TT rs2070788 TMPRSS2 SNP genotype compared to healthy controls. Conclusion: In this study conducted across multiple cities in Iran, no significant association was found between the TMPRSS2 rs2070788 SNP genotypes and COVID-19 severity or mortality.

The High-Dietary Insulin Load Score Is Associated With Elevated Level of Fasting Blood Sugar in Iranian Adult Men: Results From Fasa PERSIAN Cohort Study.

Aim: The potential of different foods to induce postprandial hyperinsulinemia may be involved in the development of metabolic syndrome (MetS). We aimed to evaluate the association between dietary insulin indices and MetS in a large population of adults in Iran. Methods: A total of 6356 adults aged 35-70 years were included in the present cross-sectional study. A validated block-format 125-item semiquantitative food frequency questionnaire (FFQ) was used to obtain usual food intakes, and MetS was defined according to the International Diabetes Federation (IDF) and American Heart Association (AHA)/National Heart, Lung, and Blood Institute (NHLBI) criteria. Results: MetS was prevalent in 13.8% of participants. Mean age of the study participants was 46.58 ± 8.82 years, and mean body mass index (BMI) was 25.02 ± 4.60 kg/m2. Mean dietary insulin index (DII) and dietary insulin load (DIL) were 63.15 ± 7.57 and 168.253 ± 52.09, respectively. In the crude model, men in the highest DIL quartile were more likely to have hyperglycemia than those in the lowest quartile (OR: 1.75, 95% CI: 1.12-2.73, p trend = 0.04). This association remained significant and was even stronger after adjusting for potential confounders in model I (OR: 3.64, 95% CI: 1.57-8.47, p trend = 0.005) and further adjustment for BMI in model II (OR: 3.61, 95% CI: 1.55-8.44, p trend = 0.006). Conclusions: In healthy men, adherence to a high-DIL diet may be associated with a greater likelihood of having hyperglycemia. No statistically significant association was observed between insulin indices and the odds of having MetS.

Consanguineous marriage among familial multiple sclerosis subjects: A national registry-based study.

Background: The rising prevalence of familial multiple sclerosis (MS) in Iran has spurred interest in the potential impact of parental consanguinity on the risk of developing the disease. This study aims to aggregate current knowledge on parental consanguinity and its possible effect on MS risk, particularly among familial MS patients from various regions and ethnicities in Iran. The objective is to enhance the understanding of MS genetics and encourage further research in this field. Materials and methods: A cross-sectional study was conducted on clinically definite familial MS (FMS) patients registered in the nationwide MS registry of Iran (NMSRI). Data were extracted and supplemented with structured telephone follow-ups to gather detailed histories of MS in relatives and the familial relationships of the patients' parents. A family penetration score was proposed. Descriptive statistics and inferential statistical tests were used to analyze the data at a significance level of 0.05, adhering to ethical guidelines. Results: Out of 19,911 individuals registered in the NMSRI, 2307 FMS patients across 13 provinces were included in the final analysis. Among these, 385 (19.3 %) reported parental consanguinity, with 283 (14.2 %) having parents who were cousins and 102 (5.1 %) having parents who were distant relatives. The data showed no significant association between parental kinship and variables such as MS phenotype, number of affected relatives with MS, hospitalization rates, and expanded disability status scale score. Similarly, MS severity did not differ based on parental consanguinity (P-value >0.05). While the rate of consanguineous marriage was higher among patients with an onset age less than 18 years, there was no statistically significant difference in disease onset age based on parental consanguinity status. Conclusion: Our study highlights the complexity of factors influencing MS development, including genetic and environmental components. These results highlight the need for further research to achieve a more comprehensive understanding of MS etiology.

Comparison of atherosclerotic cardiovascular disease (ASCVD) and Framingham risk scores (FRS) in an Iranian population.

Background: Framingham risk score (FRS) and Atherosclerotic Cardiovascular Disease risk score (ASCVDrs) are widely used tools developed based on the American population. This study aimed to compare the ASCVDrs and FRS in an Iranian population. Method: The participants of the Fasa Adult Cohort Study and the patients of the cardiovascular database of Vali-Asr Hospital of Fasa, aged 40-80 years, were involved in the present cross-sectional study. After excluding non-eligible participants, the individuals with a history of myocardial infarction or admission to the cardiology ward due to heart failure were considered high-risk, and the others were considered low-risk. The discriminative ability of FRS and ASCVDrs was evaluated and compared using receiver operating characteristic curve analysis. The correlation and agreement of ASCVDrs and FRS were tested using Cohen Kappa and Spearman. Results: Finally, 8983 individuals (mean age:53.9 ± 9.5 y, 49.2 % male), including 1827 high-risk participants, entered the study. ASCVDrs detected a greater portion of participants as high-risk in comparison with FRS (28.7 % vs. 15.7 %). ASVD (AUC:0.794) had a higher discriminative ability than FRS (AUC:0.746), and both showed better discrimination in women. Optimal cut-off points for both ASCVDrs (4.36 %) and FRS (9.05 %) were lower than the original ones and in men. Compared to FRS, ASCVDrs had a higher sensitivity (79.3 % vs. 71.6 %) and lower specificity (64.5 % vs. 65.1 %). FRS and ASCVDrs had a moderate agreement (kappa:0.593,p-value<0.001) and were significantly correlated (Spearman:0.772,p-value<0.001). Conclusions: ASCVDrs had a more accurate prediction of cardiovascular events and identified a larger number of people as high-risk in the Iranian population.

The relationship between moral courage, team work, and safe nursing care in clinical nurses: a multicenter cross-sectional study in Iran.

BACKGROUND: Moral courage and team work are the most important aspects of professional competence in clinical nurses; nurses with moral courage and team work are thought to be able to deliver safe nursing care to patients. The present study aimed to investigate whether moral courage and teamwork correlate with safe nursing care among clinical nurses. METHODS: This descriptive cross-sectional multicenter study was carried out from December 2023 to February 2024. A total of 375 nurses who were practicing in four hospitals in the south of Iran were enrolled in this study using convenience sampling. The data collection tools used consisted of a demographics survey, Moral Courage Questionnaire (MCQ), Team STEPPS Team Perception Questionnaire (T-TPQ), and the Assessment of Safe Nursing Care Questionnaire (ASNCQ). The data were analyzed using descriptive statistics, t-test, chi-square, multiple regression analysis, and Pearson's correlation coefficient. SPSS version 22 was used to analyze the data. RESULTS: The participants' mean age was 32.66 ± 6.63 years, and their work experience was 8.56 ± 6.22 years. The total mean scores for moral courage, teamwork, and safe care were 422.37 ± 52.92, 144.09 ± 18.43, 315.84 ± 41.95, respectively. A statistically significant positive correlation was found between teamwork and safe care (r = 0.57, p < 0.001), teamwork and moral courage (r = 0.49, p = 0.002), and moral courage and safe nursing care (r = 0.59 p < 0.001). According to the results, work experience, moral courage, and teamwork explained 44.4% of the variance in safe nursing care (R2 = 0.44, p < 0.001). CONCLUSION: The results indicated that the moral courage and teamwork of nurses were positively and significantly correlated with the participants' safe nursing care. Accordingly, since moral courage and teamwork are the qualities that can contribute to improving the quality of care and ensuring safe nursing care, it is recommended that nursing managers pay special attention to these factors.

Online exercise added to ergonomic advice for reducing habitual upper body postures: A randomized trial.

BACKGROUND: Online learning during the COVID-19 pandemic is associated with unfavorable habitual upper body postures. OBJECTIVE: This study explored whether adding a remedial exercise routine to an ergonomic advice intervention, delivered remotely, is helpful for reducing habitual postures of the neck, shoulders, and upper back. DESIGN: Pragmatic randomized controlled trial. METHODS: 42 male adolescent students, initially selected with a forward head posture, were randomized to one of two intervention groups: ergonomic advice alone or exercise + ergonomic advice. Outcome measures were specific postural angles of, measured by a photogrammetric profile technique using a bespoke app before and after the 8-week intervention period. RESULTS: During online learning, most students used mobile phones (76%), while 35% used a table-chair-computer arrangement. At 8-week follow-up, a statistically significant reduction of forward head, shoulder protraction, and thoracic kyphosis angles was found in both groups (P < 0.001). However, the effect was significantly greater in the exercise + ergonomic advice group (P < 0.001): forward head, shoulder protraction, and thoracic kyphosis angles reduced by some 9, 6, and 5° respectively, compared with 4° for head and 2° for shoulder and thoracic angles for the ergonomic advice alone group. CONCLUSION: The results show that, a remedial online exercise routine is a beneficial addition to an ergonomic advice program for improving unfavorable habitual upper body postures. The impact of this intervention may extend beyond postural issues related just to online learning at home.

Prevalence of Complementary and Alternative Medicine Use and Its Associated Factors among Iranian Diabetic Patients: A Cross-Sectional Study.

Objective: This cross-sectional study aimed to assess the prevalence of complementary and alternative medicine (CAM) use and its associated factors among diabetic patients in Fasa, a city in southern Iran. Methods: Data were collected from diabetic patients who visited the endocrinology clinics at Fasa University of Medical Sciences. A structured questionnaire was administered to gather information on CAM use, including the types of CAM modalities used, and reasons for use. The patient's demographic and clinical characteristics, such as age, gender, duration of diabetes, glycosylated hemoglobin (HbA1c) levels, and quality of life (QoL) were also recorded. Descriptive statistics were used to determine the prevalence of CAM use, while logistic regression analysis was employed to identify factors associated with CAM use. Results: A total of 376 diabetic patients participated in the study, with more than 89% reporting CAM use within the past year. Herbal preparations were the most commonly used type of CAM, with a prevalence rate of 99.4%. Factors associated with CAM use included patients' psychological health, attitude towards the safety of CAM, belief in the synergistic effects of combining routine medications with CAM, and previous positive experiences with CAM. Conclusion: The high prevalence of CAM use highlights the importance of considering it in diabetes management and the need for healthcare professionals' engagement in open discussions with patients about their CAM practices. Understanding the factors influencing CAM use can inform healthcare providers and policymakers in developing appropriate strategies for integrating CAM approaches into conventional diabetes care.

Evaluation of the Expression of Infection-Related Long Noncoding RNAs among COVID-19 Patients: A Case-Control Study.

Background and Aims: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a worldwide pandemic, activates signaling cascades and leads to innate immune responses and secretion of multiple chemokines and cytokines. Long noncoding RNAs (lncRNAs) have a crucial role in inflammatory pathways. Through our search on the PubMed database, we discovered that existing research has primarily focused on examining the regulatory impacts of five lncRNAs in the context of viral infections. However, their role in regulating other conditions, including SARS-CoV-2, has not been explored. Therefore, this study aimed to investigate the expression pattern of lncRNAs in the peripheral blood mononuclear cells (PBMC) and their potential roles in SARS-CoV-2 infection. Potentially significant competing endogenous RNA (ceRNA) networks of these five lncRNAs were found using online in-silico techniques. Methods: Ethylenediaminetetraacetic acid (EDTA) blood samples of the control group consisted of 45 healthy people, and a total of 53 COVID-19-infected patients in case group, with a written informed consent, was collected. PBMCs were extracted, and then, the RNA extraction and complementary DNA (cDNA) synthesis was performed. The expression of five lncRNAs (lnc ISR, lnc ATV, lnc PAAN, lnc SG20, and lnc HEAL) was assessed by real-time PCR. In order to evaluate the biomarker roles of genes, receiver operating characteristic (ROC) curve was drawn. Results: Twenty-four (53.3%) and 29 (54.7%) of healthy and COVID-19-infected participants were male, respectively. The most prevalent symptoms were as follows: cough, general weakness, contusion, headache, and sore throat. The results showed that three lncRNAs, including lnc ISR, lnc ATV, and lnc HEAL, were expressed dramatically higher in the case group compared to healthy controls. According to ROC curve analysis, lnc ATV has a higher AUC and is a better biomarker to differentiate COVID-19 patients from the healthy controls. Then, using bioinformatics methods, the ceRNA network of these lncRNAs enabled the identification of mRNAs and miRNAs with crucial functions in COVID-19. Conclusion: The considerable higher expression of ISR, ATV, and HEAL lncRNAs and the significant area under curve (AUC) in ROC curve demonstrate that these RNAs probably have a potential role in controlling the host innate immune responses and regulate the viral replication of SARS-CoV-2. However, these assumptions need further in vitro and in vivo investigations to be confirmed.

Production and Purification of Plasmodium Circumsporozoite Protein in Lactococcus lactis.

Malaria is a vector-borne disease caused by Plasmodium parasites of which Plasmodium falciparum contributed to an estimated 247 million cases worldwide in 2021 (WHO malaria report 2022). The P. falciparum Circumsporozoite protein (PfCSP) covers the surface of the sporozoite which is critical to cell invasion in the human host. PfCSP is the leading pre-erythrocytic vaccine candidate and forms the basis of the RTS'S (Mosquirix®) malaria vaccine. However, high-yield production of full-length PfCSP with proper folding has been challenging. Here, we describe expression and purification of full-length PfCSP (containing 4 NVDP and 38 NANP repeats) with proper conformation by a simple three-step procedure in the Lactococcus lactis expression system.

Clinical formulation development of Plasmodium falciparum malaria vaccine candidates based on Pfs48/45, Pfs230, and PfCSP.

Two malaria transmission-blocking vaccine (TBV) candidates, R0.6C and ProC6C, have completed preclinical development including the selection of adjuvants, Alhydrogel® with or without the saponin based adjuvant Matrix-M™. Here, we report on the final drug product (formulation) design of R0.6C and ProC6C and evaluate their safety and biochemical stability in preparation for preclinical and clinical pharmacy handling. The point-of-injection stability studies demonstrated that both the R0.6C and ProC6C antigens are stable on Alhydrogel in the presence or absence of Matrix-M for up to 24 h at room temperature. As this is the first study to combine Alhydrogel and Matrix-M for clinical use, we also evaluated their potential interactions. Matrix-M adsorbs to Alhydrogel, while not displacing the > 95 % adsorbed protein. The R0.6C and ProC6C formulations were found to be safe and well tolerated in repeated dose toxicity studies in rabbits generating high levels of functional antibodies that blocked infection of mosquitoes. Further, the R0.6C and ProC6C drug products were found to be stable for minimally 24 months when stored at 2-8 °C, with studies ongoing through 36 months. Together, this data demonstrates the safety and suitability of the L. lactis expression system as well as supports the clinical testing of the R0.6C and ProC6C malaria vaccine candidates in First-In-Human clinical trials.

A randomized first-in-human phase I trial of differentially adjuvanted Pfs48/45 malaria vaccines in Burkinabé adults.

BACKGROUNDMalaria transmission-blocking vaccines aim to interrupt the transmission of malaria from one person to another.METHODSThe candidates R0.6C and ProC6C share the 6C domain of the Plasmodium falciparum sexual-stage antigen Pfs48/45. R0.6C utilizes the glutamate-rich protein (GLURP) as a carrier, and ProC6C includes a second domain (Pfs230-Pro) and a short 36-amino acid circumsporozoite protein (CSP) sequence. Healthy adults (n = 125) from a malaria-endemic area of Burkina Faso were immunized with 3 intramuscular injections, 4 weeks apart, of 30 µg or 100 µg R0.6C or ProC6C each adsorbed to Alhydrogel (AlOH) adjuvant alone or in combination with Matrix-M (15 µg or 50 µg, respectively). The allocation was random and double-blind for this phase I trial.RESULTSThe vaccines were safe and well tolerated with no vaccine-related serious adverse events. A total of 7 adverse events, mild to moderate in intensity and considered possibly related to the study vaccines, were recorded. Vaccine-specific antibodies were highest in volunteers immunized with 100 µg ProC6C-AlOH with Matrix-M, and 13 of 20 (65%) individuals in the group showed greater than 80% transmission-reducing activity (TRA) when evaluated in the standard membrane feeding assay at 15 mg/mL IgG. In contrast, R0.6C induced sporadic TRA.CONCLUSIONAll formulations were safe and well tolerated in a malaria-endemic area of Africa in healthy adults. The ProC6C-AlOH/Matrix-M vaccine elicited the highest levels of functional antibodies, meriting further investigation.TRIAL REGISTRATIONPan-African Clinical Trials Registry (https://pactr.samrc.ac.za) PACTR202201848463189.FUNDINGThe study was funded by the European and Developing Countries Clinical Trials Partnership (grant RIA2018SV-2311).

Home schooling during the COVID-19 pandemic: A randomized controlled trial of online exercise and ergonomics advice protocols on upper body symptoms.

BACKGROUND: Understanding of students' musculoskeletal health under home-schooling during the COVID-19 pandemic is limited. OBJECTIVES: (1) To investigate the prevalence and severity of musculoskeletal symptoms in home-schooled adolescents during the COVID-19 pandemic. (2) To evaluate the effect of an online exercise + ergonomics advice protocol on symptoms, compared with ergonomics advice alone. DESIGN: Cross-sectional symptom survey identifying eligible participants, followed by a pragmatic randomized controlled trial. SETTING: Online classes. PARTICIPANTS: Survey: 354 students (mean 16.6 years). TRIAL: 188 students with upper body musculoskeletal symptoms. INTERVENTIONS: Randomization to three groups (physical therapy exercises + ergonomics postural advice, ergonomics postural advice alone, nonintervention control) stratified by the site of symptoms (neck, shoulder, upper back). Interventions were orally delivered online (via WhatsApp) supplemented with written/illustrative material. Follow-up occurred at 8 weeks. OUTCOME MEASURES: Survey: prevalence of symptoms (Nordic Questionnaire). TRIAL: primary outcome = change in intensity of upper body symptoms (visual analogue scale); secondary outcome = number of participants reporting improvement in upper body symptoms. RESULTS: The 12-month prevalence of musculoskeletal disorders in the survey was 38% neck, 28% shoulder, and 35% upper back, with mean pain intensity of 3.6, 3.9, and 3.8, respectively, on 0-10 visual analogue scale: Two-thirds reported symptoms in multiple anatomical regions. In the trial, there was no statistically significant difference between the exercise + ergonomics group and ergonomics alone group on the primary outcome, yet both groups showed reduced symptom intensity compared with control (p < .001). More participants in the exercise + ergonomics group reported improvement than in the ergonomics advice alone group (p < .02). CONCLUSIONS: The prevalence of musculoskeletal symptoms was relatively high in home-schooled adolescents. Symptoms can be reduced by ergonomics advice with or without exercises, but the effect is enhanced by the addition of physical therapy exercises. The latter approach may be considered for improving schoolchildren's musculoskeletal health in the usual classroom setting.

Food co-consumption network as a new approach to dietary pattern in non-alcoholic fatty liver disease.

Dietary patterns strongly correlate with non-alcoholic fatty liver disease (NAFLD), which is a leading cause of chronic liver disease in developed societies. In this study, we introduce a new definition, the co-consumption network (CCN), which depicts the common consumption patterns of food groups through network analysis. We then examine the relationship between dietary patterns and NAFLD by analyzing this network. We selected 1500 individuals living in Tehran, Iran, cross-sectionally. They completed a food frequency questionnaire and underwent scanning via the FibroScan for liver stiffness, using the CAP score. The food items were categorized into 40 food groups. We reconstructed the CCN using the Spearman correlation-based connection. We then created healthy and unhealthy clusters using the label propagation algorithm. Participants were assigned to two clusters using the hypergeometric distribution. Finally, we classified participants into two healthy NAFLD networks, and reconstructed the gender and disease differential CCNs. We found that the sweet food group was the hub of the proposed CCN, with the largest cliques of size 5 associated with the unhealthy cluster. The unhealthy module members had a significantly higher CAP score (253.7 ± 47.8) compared to the healthy module members (218.0 ± 46.4) (P < 0.001). The disease differential CCN showed that in the case of NAFLD, processed meat had been co-consumed with mayonnaise and soft drinks, in contrast to the healthy participants, who had co-consumed fruits with green leafy and yellow vegetables. The CCN is a powerful method for presenting food groups, their consumption quantity, and their interactions efficiently. Moreover, it facilitates the examination of the relationship between dietary patterns and NAFLD.

An insight into the potential role of LINC00968 in luminal breast cancer: Case-control study and bioinformatics analysis.

Background: Luminal A and B subtypes of breast cancer (BC) comprises up to 70% of all BC patients. LncRNAs can affect many biological and pathological processes, and dysregulation of them is related to human cancers. The potential role of lncRNA LINC00968 in luminal BC is still unclear. Materials and methods: We analyzed the LINC00968 expression across 44 paired luminal BC tissues from the TCGA-BRCA RNA sequencing dataset. Besides, we used the GEPIA2 web server and GENEVESTIGATOR software, as well. Real-Time Quantitative Reverse Transcription PCR (qRT-PCR) assay was performed to confirm the LINC00968 expression in 71 paired luminal BC tissues and two luminal A cell lines (MCF7 and T47D). Moreover, to better understanding the potential role of LINC00968 in luminal BC, computational data analyses including co-expression analysis, functional annotation analysis, and genetic alteration analysis have been done. Results: The results of data analyses retrieved from BRCA dataset and databases revealed the significant downregulation of LINC00968 in luminal A and B BC. Also, the results of qRT-PCR in luminal BC tissues and cell lines confirmed the earlier data. LINC00968 expression was negatively associated with tumor stage and lymph node metastasis. Additionally, functional annotation analyses revealed that LINC00968 might be involved in vascular development and angiogenesis, extracellular matrix organization, and cell motility and migration. LINC00968 might play role in some cancer-related signaling pathways. Conclusion: Our study found that downregulation of LINC00968 might promote tumorigenesis, invasion, and metastasis of luminal BC.

Insilco prediction of the role of the FriZZled5 gene in colorectal cancer.

INTRODUCTION: In this study, we aimed to elucidate the crosstalk between the Wnt/ß-catenin signaling pathway and colorectal cancer (CRC) associated with inflammatory bowel disease (IBD) using a bioinformatics analysis of putative common biomarkers and a systems biology approach. MATERIALS AND METHODS: The following criteria were used to search the GEO and ArrayExpress databases for terms related to CRC and IBD: 1. The dataset containing the transcriptomic data, and 2. Untreated samples by medications or drugs. A total of 42 datasets were selected for additional analysis. The GEO2R identified the differentially expressed genes. The genes involved in the Wnt signaling pathway were extracted from the KEGG database. Enrichment analysis and miRNA target prediction were conducted through the ToppGene online tool. RESULTS: In CRC datasets, there were 1168 up- and 998 down-regulated probes, whereas, in IBD datasets, there were 256 up- and 200 down-regulated probes. There were 65 upregulated and 57 downregulated genes shared by CRC and IBD. According to KEGG, there were 166 genes in the Wnt pathway. FriZZled5 (FZD5) was a down-regulated gene in both CRC and IBD, as determined by the intersection of CRC- and IBD-related DEGs with the Wnt pathway. It was also demonstrated that miR-191, miR-885-5p, miR-378a-3p, and miR-396-3p affect the FriZZled5 gene expression. CONCLUSION: It is possible that increased expression of miR-191 and miR-885-5p, or decreased expression of miR-378a -3p and miR396-3, in IBD and CRC results in decreased expression of the FZD5 gene. Based on the function of this gene, FZD5 may be a potential therapeutic target in IBD that progresses to CRC.

Effect of tofacitinib on clinical and laboratory findings in severe and resistant patients with COVID-19.

BACKGROUND: The efficacy and safety of a strong Janus kinase inhibitor, tofacitinib, in individuals suffering from severe coronavirus disease 2019 (Covid-19) pneumonia are not definite well. METHODS: In this non-randomized and non-blinded trial, a total of 52 Iranian patients with severe COVID-19 associated with decreased oxygen saturation, elevated C-reactive protein, and/or persistent fever were included. A total of 52 patients were included in this study. Tofacitinib was administered to 29 patients (55.8%) in addition to the standard care treatments, whereas 23 patients (44.2%) were treated with the standard of care alone (mostly antiviral agents and corticosteroids). Tofacitinib was administered at a dose of 5 mg twice daily for up to 10 days. The primary outcomes were mortality rate, oxygen saturation level, CT findings, rate of breath, heart rate, and level of consciousness. Inflammatory cytokines and blood biomarkers were considered as the secondary outcomes. RESULTS: Death from any cause through day 14 occurred in 51.7% of the tofacitinib group and 65.2% of the control group. There was no significant difference in lung radiographic findings between the intervention and control groups at the first day of the study and after the study period. However, a significant decrease was observed in the extent of lung tissue involvement in the intervention group after administration of tofacitinib. Regarding cell and blood biomarkers, a significant decrease in the CPK levels in the intervention group and Hct and ACE levels in the control group was observed after fourteen days of the study. Moreover, a significant increase in SGOT and ferritin values was detected in the control group 14 days after the beginning tofacitinib administration. Comparing control and intervention groups, there was a significant difference in hemoglobin, SGOT, LDH, ferritin, and ACE values between groups before the intervention, while after fourteen days of the study, no significant difference was found. In case of DHEAS and TSH levels, a significant decrease was seen in the intervention group compared to the control after the study period. No other significant improvement was detected in other outcomes of the tofacitinib group compared to the control. CONCLUSIONS: The administration of tofacitinib combined with corticosteroids, is not effective enough to treat severe COVID-19 patients and the use of this medication should be considered before the disease deterioration.

Human blood neutrophils generate ROS through FcγR-signaling to mediate protection against febrile P. falciparum malaria.

Blood phagocytes, such as neutrophils and monocytes, generate reactive oxygen species (ROS) as a part of host defense response against infections. We investigated the mechanism of Fcγ-Receptor (FcγR) mediated ROS production in these cells to understand how they contribute to anti-malarial immunity. Plasmodium falciparum merozoites opsonized with naturally occurring IgG triggered both intracellular and extracellular ROS generation in blood phagocytes, with neutrophils being the main contributors. Using specific inhibitors, we show that both FcγRIIIB and FcγRIIA acted synergistically to induce ROS production in neutrophils, and that NADPH oxidase 2 and the PI3K intracellular signal transduction pathway were involved in this process. High levels of neutrophil ROS were also associated with protection against febrile malaria in two geographically diverse malaria endemic regions from Ghana and India, stressing the importance of the cooperation between anti-malarial IgG and neutrophils in triggering ROS-mediated parasite killing as a mechanism for naturally acquired immunity against malaria.

The relationship between pregnancy count and duration of breast-feeding with metabolic syndrome (Fasa Persian cohort study).

BACKGROUND: Changes that occur during pregnancy and after that during breastfeeding induce some symptoms similar to metabolic syndrome (MetS) risk factors. This study aims to determine the relationship between pregnancy, as well as the duration of breastfeeding and MetS controlling the effect of other risk factors like hypertension, glucose intolerance, triglyceride, central obesity, and reduction of high-density lipoprotein in women of Fasa Persian Cohort Study. MATERIALS AND METHODS: In this cross-sectional study, 5015 women aged 35-70 years were investigated in the Sheshdeh region from 2016 to 2021, and the information related to the disease symptoms was collected through questionnaires, examinations, and laboratory tests. MetS was calculated based on two guidelines according to adult treatment panel III (ATP III) and international diabetes federation (IDF) methods. For reporting the data, the odds ratio with its 95% confidence interval was used. In order to eliminate the effect of confounders, logistic regression was used. RESULTS: Prevalence of MetS showed a descending trend in women with up to two pregnancies and it reached 22.6% and 22.4% using ATPIII and IDF methods respectively, while with an increase in the number of pregnancies of more than two, MetS prevalence was ascending. The prevalence of MetS did not have any specific trend across various breastfeeding duration groups. Multivariate analysis approved that the odds ratio of developing MetS in comparison with women who had two pregnancies was significantly increasing trend when the pregnancy counts increased. CONCLUSION: The chance of developing MetS based on both IDF and ATP III methods after adjustment for confounding effects would grow with an increase in the number of pregnancies to more than two and breast-feeding of more than seven years. It is recommended that women with more than two pregnancies or the long duration of breast-feeding women undergo a specialized examination to investigate and control MetS problems so that future diseases could be prevented.