IL-2RG as a possible immunotherapeutic target in CRC predicting poor prognosis and regulated by miR-7-5p and miR-26b-5p.

Despite advances in treatment strategies, colorectal cancer (CRC) continues to cause significant morbidity and mortality, with mounting evidence a close link between immune system dysfunctions issued. Interleukin-2 receptor gamma (IL-2RG) plays a pivotal role as a common subunit receptor in the IL-2 family cytokines and activates the JAK-STAT pathway. This study delves into the role of Interleukin-2 receptor gamma (IL-2RG) within the tumor microenvironment and investigates potential microRNAs (miRNAs) that directly inhibit IL-2RG, aiming to discern their impact on CRC clinical outcomes. Bioinformatics analysis revealed a significant upregulation of IL-2RG mRNA in TCGA-COAD samples and showed strong correlations with the infiltration of various lymphocytes. Single-cell analysis corroborated these findings, highlighting IL-2RG expression in critical immune cell subsets. To explore miRNA involvement in IL-2RG dysregulation, mRNA was isolated from the tumor tissues and lymphocytes of 258 CRC patients and 30 healthy controls, and IL-2RG was cloned into the pcDNA3.1/CT-GFP-TOPO vector. Human embryonic kidney cell lines (HEK-293T) were transfected with this construct. Our research involved a comprehensive analysis of miRPathDB, miRWalk, and Targetscan databases to identify the miRNAs associated with the 3' UTR of human IL-2RG. The human microRNA (miRNA) molecules, hsa-miR-7-5p and hsa-miR-26b-5p, have been identified as potent suppressors of IL-2RG expression in CRC patients. Specifically, the downregulation of hsa-miR-7-5p and hsa-miR-26b-5p has been shown to result in the upregulation of IL-2RG mRNA expression in these patients. Prognostic evaluation of IL-2RG, hsa-miR-7-5p, and hsa-miR-26b-5p, using TCGA-COAD data and patient samples, established that higher IL-2RG expression and lower expression of both miRNAs were associated with poorer outcomes. Additionally, this study identified several long non-coding RNAs (LncRNAs), such as ZFAS1, SOX21-AS1, SNHG11, SNHG16, SNHG1, DLX6-AS1, GAS5, SNHG6, and MALAT1, which may act as competing endogenous RNA molecules for IL2RG by sequestering shared hsa-miR-7-5p and hsa-miR-26b-5p. In summary, this investigation underscores the potential utility of IL-2RG, hsa-miR-7-5p, and hsa-miR-26b-5p as serum and tissue biomarkers for predicting CRC patient prognosis while also offering promise as targets for immunotherapy in CRC management.

Immunologic responses to the third and fourth doses of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines in cell therapy recipients: a systematic review and meta-analysis.

BACKGROUND: Multiple studies have provided evidence of suboptimal or poor immune responses to SARS-CoV-2 vaccines in recipients of hematopoietic stem cell transplantation (HSCT) and chimeric antigen receptor-T (CAR-T) cell therapy compared to healthy individuals. Given the dynamic nature of SARS-CoV2, characterized by the emergence of many viral variations throughout the general population, there is ongoing discussion regarding the optimal quantity and frequency of additional doses required to sustain protection against SARS-CoV2 especially in this susceptible population. This systematic review and meta-analysis investigated the immune responses of HSCT and CAR-T cell therapy recipients to additional doses of the SARS-CoV-2 vaccines. METHODS: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, the study involved a comprehensive search across PubMed, Scopus, Web of Science Core Collection, Embase, and Cochrane Biorxiv and medRxiv, focusing on the serological responses to the third and fourth vaccine doses in HSCT and CAR-T cell patients. RESULTS: This study included 32 papers, with 31 qualifying for the meta-analysis. Results showed that after the third dose, the seroconversion rate in HSCT and CAR-T cell therapy recipients who didn't respond to the second dose was 46.10 and 17.26%, respectively. Following the fourth dose, HSCT patients had a seroconversion rate of 27.23%. Moreover, post-third-dose seropositivity rates were 87.14% for HSCT and 32.96% for CAR-T cell therapy recipients. Additionally, the seropositive response to the fourth dose in the HSCT group was 90.04%. CONCLUSION: While a significant portion of HSCT recipients developed antibodies after additional vaccinations, only a minority of CAR-T cell therapy patients showed a similar response. This suggests that alternative vaccination strategies are needed to protect these vulnerable groups effectively. Moreover, few studies have reported cellular responses to additional SARS-CoV-2 vaccinations in these patients. Further studies evaluating cellular responses are required to determine a more precise assessment of immunogenicity strength against SARS-CoV-2 after additional doses.

Exploring the association between ultra-processed foods and COPD: a case-control study.

BACKGROUND: While it is known that the overconsumption of ultra-processed foods (UPFs) is associated with a heightened risk of respiratory ailments, the specific effects of UPF intake on COPD remain unclear. This study was designed to explore the potential link between COPD and the consumption of UPFs among adult individuals in Iran. METHODS: In this hospital-based case-control study conducted at Alzahra University Hospital in Isfahan, Iran, we enrolled 84 patients newly diagnosed with COPD, along with 252 healthy controls matched for age and sex. COPD was defined based on the results of spirometry tests, specifically when the forced expiratory volume per second (FEV1) was less than 80% or the ratio of FEV1 to forced vital capacity (FVC) was less than 70%. To evaluate the dietary intake of the participants, we utilized a validated food frequency questionnaire (FFQ) consisting of 168 items. Additionally, we gathered data on potential confounding factors using a pre-tested questionnaire. RESULTS: The mean ages for the case and control groups were 57.07 and 55.05 years, respectively. Our study found no significant association between the intake of ultra-processed foods (UPFs) and the likelihood of COPD, with an odds ratio (OR: 0.78, 95% CI: 0.34-1.77). This lack of association persisted even after adjusting for factors such as energy intake, sex, and age (OR: 0.48; 95% CI: 0.19-1.21). Further controlling for potential confounders like body mass index (BMI), physical activity, and smoking status did not alter this finding (OR: 0.367; 95% CI: 0.123-1.1008, P = 0.074). CONCLUSIONS: In our study, we observed no significant association between the intake of Ultra-Processed Foods (UPFs) and the odds of Chronic Obstructive Pulmonary Disease (COPD). This finding remained consistent even after adjusting for factors such as energy intake, sex, age, Body Mass Index (BMI), physical activity, and smoking status. Therefore, within the scope of our study, it appears that the consumption of UPFs does not significantly impact the likelihood of developing COPD. However, we recommend further research to deepen our understanding of the intricate relationship between dietary habits and respiratory health.

Dietary patterns and micronutrients in respiratory infections including COVID-19: a narrative review.

BACKGROUND: COVID-19 is a pandemic caused by nCoV-2019, a new beta-coronavirus from Wuhan, China, that mainly affects the respiratory system and can be modulated by nutrition. METHODS: This review aims to summarize the current literature on the association between dietary intake and serum levels of micronutrients, malnutrition, and dietary patterns and respiratory infections, including flu, pneumonia, and acute respiratory syndrome, with a focus on COVID-19. We searched for relevant articles in various databases and selected those that met our inclusion criteria. RESULTS: Some studies suggest that dietary patterns, malnutrition, and certain nutrients such as vitamins D, E, A, iron, zinc, selenium, magnesium, omega-3 fatty acids, and fiber may have a significant role in preventing respiratory diseases, alleviating symptoms, and lowering mortality rates. However, the evidence is not consistent and conclusive, and more research is needed to clarify the mechanisms and the optimal doses of these dietary components. The impact of omega-3 and fiber on respiratory diseases has been mainly studied in children and adults, respectively, and few studies have examined the effect of dietary components on COVID-19 prevention, with a greater focus on vitamin D. CONCLUSION: This review highlights the potential of nutrition as a modifiable factor in the prevention and management of respiratory infections and suggests some directions for future research. However, it also acknowledges the limitations of the existing literature, such as the heterogeneity of the study designs, populations, interventions, and outcomes, and the difficulty of isolating the effects of single nutrients from the complex interactions of the whole diet.

p38 MAPK signaling in chronic obstructive pulmonary disease pathogenesis and inhibitor therapeutics.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterized by persistent respiratory symptoms and airflow limitation due to airway and/or alveolar remodeling. Although the abnormalities are primarily prompted by chronic exposure to inhaled irritants, maladjusted and self-reinforcing immune responses are significant contributors to the development and progression of the disease. The p38 isoforms are regarded as pivotal hub proteins that regulate immune and inflammatory responses in both healthy and disease states. As a result, their inhibition has been the subject of numerous recent studies exploring their therapeutic potential in COPD. MAIN BODY: We performed a systematic search based on the PRISMA guidelines to find relevant studies about P38 signaling in COPD patients. We searched the PubMed and Google Scholar databases and used "P38" AND "COPD" Mesh Terms. We applied the following inclusion criteria: (1) human, animal, ex vivo and in vitro studies; (2) original research articles; (3) published in English; and (4) focused on P38 signaling in COPD pathogenesis, progression, or treatment. We screened the titles and abstracts of the retrieved studies and assessed the full texts of the eligible studies for quality and relevance. We extracted the following data from each study: authors, year, country, sample size, study design, cell type, intervention, outcome, and main findings. We classified the studies according to the role of different cells and treatments in P38 signaling in COPD. CONCLUSION: While targeting p38 MAPK has demonstrated some therapeutic potential in COPD, its efficacy is limited. Nevertheless, combining p38 MAPK inhibitors with other anti-inflammatory steroids appears to be a promising treatment choice. Clinical trials testing various p38 MAPK inhibitors have produced mixed results, with some showing improvement in lung function and reduction in exacerbations in COPD patients. Despite these mixed results, research on p38 MAPK inhibitors is still a major area of study to develop new and more effective therapies for COPD. As our understanding of COPD evolves, we may gain a better understanding of how to utilize p38 MAPK inhibitors to treat this disease. Video Abstract.

We wanted to determine what studies have been done on how a protein called p38 affects a lung disease called COPD. COPD is a condition that makes it hard to breathe and can cause coughing, wheezing, and chest infections. p38 is a protein that helps cells to respond to stress and inflammation, but it may also play a role in causing or worsening COPD. We searched two main online databases for studies that met our criteria. We looked for studies that involved humans, studies that used animals or cells in the lab, studies that reported new findings, studies that were written in English, and studies that focused on p38 and COPD. We did not include studies that were reviews, summaries, opinions, or letters or studies that were not related to p38 or COPD. We found 361 studies that matched our criteria. We read the titles and summaries of these studies and checked the full texts for quality and relevance. We collected information from each study, such as who did it, when and where it was done, how many people were involved, what type of cells were studied, what treatment was given, what outcome was measured, and what the main results were. We grouped the studies based on the type of cells and type of treatment they studied. We found that different types of cells (such as lung cells, immune cells, and blood cells) and different types of treatment can affect how p38 works in COPD.

Clinical epidemiology of pulmonary aspergillosis in hospitalized patients and contribution of Cyp51A, Yap1, and Cdr1B mutations to voriconazole resistance in etiologic Aspergillus species.

Pulmonary aspergillosis is a life-threatening fungal infection with worldwide distribution. In the present study, clinical epidemiology of pulmonary aspergillosis and antifungal susceptibility of etiologic Aspergillus species were evaluated in one-hundred fifty patients with special focus on the frequency of voriconazole resistance. All the cases were confirmed by the clinical pictures, laboratory findings, and isolation of etiologic Aspergillus species which belonged to two major species, i.e., A. flavus and A. fumigatus. Seventeen isolates displayed voriconazole MIC greater than or equal to the epidemiological cutoff value. Expression of cyp51A, Cdr1B, and Yap1 genes was analyzed in voriconazole-intermediate/resistant isolates. In A. flavus, Cyp51A protein sequencing showed the substitutions T335A and D282E. In the Yap1 gene, A78C replacement led to Q26H amino acid substitution that was not reported previously in A. flavus resistant to voriconazole. No mutations associated with voriconazole resistance were found in the three genes of A. fumigatus. The expression of Yap1 was higher than that of two other genes in both A. flavus and A. fumigatus. Overall, voriconazole-resistant strains of both A. fumigatus and A. flavus demonstrated overexpression of Cdr1B, Cyp51A, and Yap1 genes compared to voriconazole-susceptible strains. Although there are still ambiguous points about the mechanisms of azole resistance, our results showed that mutations were not present in majority of resistant and intermediate isolates, while all of these isolates showed overexpression in all three genes studied. As a conclusion, it seems that the main reason of the emergence of mutation in voriconazole-resistant isolates of A. flavus and A. fumigatus is previous or prolonged exposure to azoles.

Long non­coding RNA LINC00460 contributes as a potential prognostic biomarker through its oncogenic role with ANXA2 in colorectal polyps.

BACKGROUND: Long intergenic non-coding RNA 460 (LINC00460) as a potential oncogene and Annexin A2 (ANXA2) as a promoter in different cancer progression processes was considered. A significant relationship between the LINC00460 and ANXA2 has been recently discovered in colorectal cancer (CRC). Therefore, defining molecular biomarkers accompanied by lesion histopathologic features can be a suggestive prognostic biomarker in precancerous polyps. This study aimed to investigate the elusive expression pattern of ANXA2 and LINC00460 in polyps. MATERIALS AND METHODS: The construction of the co-expression and correlation network of LINC00460 and ANXA2 was plotted. LINC00460 and ANXA2 expression in 40 colon polyps was quantified by reverse transcription-real-time polymerase chain reaction. The receiver operating characteristic (ROC) curve was designed for distinguishing the high-risk precancerous lesion from the low-risk. Further, bioinformatics analysis was applied to find the shared MicroRNA-Interaction-Targets (MITs) between ANXA2 and LINC00460, and the associated pathways. RESULTS: ANXA2 has a high co-expression rank with LINC00460 in the lncHUB database. Overexpression of ANXA2 and LINC00460 was distinguished in advanced adenoma polyps compared to the adjacent normal samples. The estimated AUC for ANXA2 and LINC00460 was 0.88 - 0.85 with 93%-90% sensitivity and 81%-70% specificity. In addition, eight MITs were shared between ANXA2 and LINC00460. Enrichment analysis detected several GO terms and pathways, including HIF-1α associated with cancer development. CONCLUSION: In conclusion, the expression of the ANXA2 and LINC00460 were significantly elevated in pre-cancerous polyps, especially in high-risk adenomas. Collectively, ANXA2 and LINC00460 may be administered as potential prognostic biomarkers in patients with a precancerous large intestine lesion as an alarming issue.

The impact of social support, physical and psychological performance on sleep outcomes in Iranian older adults: a case-control study.

BACKGROUND: Sleep quality is one of the most important factors to improve the quality of life in older adults and physical and mental health plays an essential role in better sleep quality. This study aimed to determine the impact of social support, and physical and psychological performance on sleep outcomes in Iranian older adults. METHODS: In this case-control study, 400 elder people, who were exposed to sleep problems, and 400 people without sleep problems were randomly selected during 2016-2017 in Amirkola, Iran. Subjects in the case and control groups were matched in terms of gender and age. The demographic characteristics, Duke Social Support Questionnaire (DSSI), Physical Activity Scale for the Elderly (PASE), Activity of Daily Living (ADL), Instrumental Activity of Daily Living (IADL), Mini-Mental State Examination (MMSE), and Pittsburgh Sleep Quality Questionnaire (PSQI) questionnaires were used to collect data. T-test, Chi-square, Pearson Correlation coefficient, and multiple Logistic regression were used for data analysis. RESULTS: The mean score of DSSI and its domains including social interaction (DSSI.Int) and social satisfaction (DSSI.Sat) were 28.15 ± 3.55, 9.31 ± 1.23, and 18.84 ± 2.88 in the case group and 28.87 ± 3.20, 9.48 ± 1.10, and 19.83 ± 2.44 in the control group, respectively. In this study, the mean scores of MMSE, PASE, ADL, and IADL were 25.36 ± 3.95, 101.71 ± 56.99, 13/97 ± 0.37, 20.59 ± 2/79; respectively. There was a significant inverse correlation between poor sleep quality with DSSI score (rho = -0.165, P < 0.0001), DSSI.Int (rho = -0.113, P < 0.001), DSSI.Sat (rho = -0.160, P < 0.0001), PASE (rho=-0.160, P < 0.0001), and IADL (rho = -0.112, P < 0.001) score. Therefore, more social support and physical activity improved the quality of sleep. There was a significant negative relationship between DSSI, and its domains with sleep quality in terms of gender. DSSI (rho = 0.25, P < 0.0001), DSSI.Int (P < 0.0001, rho=-0.18), and DSSI.Sat (P < 0.0001, rho=-0.22) was significant in men but not in women. The results of the adjusted logistic regression revealed a significant association between sleep quality problems and DSSI (p < 0.045, OR = 1.40), the use of hypnotic drugs (p < 0.0001, OR = 7.56), and occupation (p <0.03, OR= 12.66). CONCLUSIONS: The results of the present study suggest that low social support and all its domains, PASE, IADL, and using hypnotic drugs may play a role in the development of sleep problems. It can be used as an effective, safe, and low-cost strategy for promoting sleep quality in older adults.

Available and total phosphorus background levels in soils: a calcareous and semi-arid region.

It is critical to understand the risk of element pollution in soils by evaluating their background levels. Phosphorus (P) content in agricultural soils needs to be assessed from agronomic and environmental standpoints. The current study intended to calculate the background levels of available and total P in soils. To achieve this goal, 50 sites without human activities were selected. Soils were sampled from the surface and subsurface of each site (100 soil samples). The available P forms in soils were extracted using the water-extractable P (WEP), calcium chloride-extractable P (CCEP), and Olsen-extractable P (OEP) methods. The first two extractants are being used to evaluate P leaching from soils, while the last one is being used as an agronomic indicator. The methods used to calculate background levels were the iterative 2-δ technique (2-δ) and the calculated distribution function (CDF). Results showed that the upper limits of background levels using 2-δ method were 1.45, 0.92, 8.12, and 424.4 mg kg-1 for WEP, CCEP, OEP, and total P, respectively. Also, the upper limits of background levels using CDF method were 1.42, 1.15, 12.09, and 447.6 mg kg-1, for WEP, CCEP, OEP, and total P, respectively. It can be concluded that using these background levels, which for the first time were calculated for P, would enable us to have an accurate examination of P excess as a result of human activities.

Molecular epidemiology, antifungal susceptibility, and ERG11 gene mutation of Candida species isolated from vulvovaginal candidiasis: Comparison between recurrent and non-recurrent infections.

Vulvovaginal candidiasis (VVC) is a prevalent infection of the genitourinary tract affecting millions of women worldwide. In the present study, the importance of virulence factors, ERG11 gene mutations, ERG11 gene expression, and plasma membrane ergosterol content for fluconazole resistance in Candida species was investigated in 200 women suspected of vulvovaginitis. Isolated Candida species were identified using the ITS-restriction fragment length polymorphism (ITS-RFLP) technique. Antifungal susceptibility testing was performed according to the CLSI document. ERG11 gene expression was analyzed using real-time PCR. ERG11 gene mutation analysis was performed using sequencing methods, and the ergosterol content of the cell membrane was determined in fluconazole-resistant isolates. Furthermore, the production of phospholipase and proteinase enzymes was evaluated in recurrent and non-recurrent infections. VVC was diagnosed in 101 (50.5%) of the 200 clinical cases, of which 21 (20.8%) were confirmed as RVVC. Candida albicans was the most prevalent species, followed by C. glabrata, C. tropicalis, C. krusei, C. parapsilosis, and C. guilliermondii. Ketoconazole and fluconazole were the most effective drugs against C. albicans among five tested antifungals with MIC ranges between 0.06 and 16 µg/mL and 0.25-64 µg/mL. Substitutions of A114S, Y257H, T123I and A114V were detected in fluconazole-resistant C. albicans. The ergosterol content of the fungal cell membrane and the mean levels of ERG11 gene expression transcript were higher in fluconazole-resistant C. albicans isolates obtained from RVVC than in those obtained from VVC cases. Phospholipase and proteinase were produced in different amounts in all Candida species isolated from VVC and RVVC cases. In this review, our results demonstrated that several molecular mechanisms, including ERG11 gene expression, changes in the cell membrane ergosterol content, and mutations in ERG11 gene alone or simultaneously involved in fluconazole resistance of C. albicans species and the recurrence of VVC.

The Effects of Synbiotic Supplementation on Serum Anti-Inflammatory Factors in the Survivors of Breast Cancer with Lymphedema following a Low Calorie Diet: A Randomized, Double-Blind, Clinical Trial.

BACKGROUND AND AIM: Breast cancer-related lymphedema (BCRL) is a treatment-related inflammatory complication in breast cancer survivors (BCSs). This study was aimed to evaluate the effect of synbiotic supplementation on serum concentrations of IL-10, TGF-ß, VEGF, adiponectin, and edema volume among overweight or obese BCSs with lymphedema following a low-calorie diet (LCD). METHOD: In a randomized double-blind, controlled clinical trial, 88 obese and overweight BCSs women were randomized to synbiotic supplement (n = 44) or placebo (n = 44) groups and both groups followed an LCD for 10 weeks. Pre- and post-intervention comparisons were made regarding the anti-inflammatory markers which included IL-10, TGF-ß, VEGF, adiponectin, edema volume, and anthropometric measurements. Also, the same factors were analyzed to find inter-group disparities. RESULTS: There were no significant differences among participants in the baseline, except for IL-10 and adiponectin. Post-intervention, no significant differences were observed regarding the anti-inflammatory markers, including IL-10, VEGF, adiponectin, and TGF-ß between the groups. After 10 weeks of intervention edema volume significantly decreased in the synbiotic group; additionally, anthropometric measurements (body weight, BMI, body fat percent, and WC) decreased in both groups significantly (P < 0.001 and P < 0.005; respectively). CONCLUSION: Synbiotic supplementation coupled with an LCD in a 10-week intervention had beneficial effects on increasing the serum TGF-ß, IL-10, and adiponectin levels in women with BCRL. It also reduced arm lymphedema volume. Therefore, synbiotic supplementation can be effective in improving health status in BCRL patients.

Epidemiology of familial multiple sclerosis in Iran: a national registry-based study.

BACKGROUND: Admittedly, little is known about the epidemiological signatures of familial multiple sclerosis (FMS) in different geographical regions of Iran. OBJECTIVE: To determine the epidemiology and the risk of FMS incidence in several provinces of Iran with a different ethnic population including, Fars, Tehran, Isfahan (Persians), and Mazandaran (Mazanis), Kermanshah (Kurds), and Chaharmahal and Bakhtiari (Lors). METHODS: This cross-sectional registry-based study was performed on nationwide MS registry of Iran (NMSRI) data collected from 2018 to 2021. This system, registers baseline characteristics, clinical presentations and symptoms, diagnostic and treatments at regional and national levels. RESULTS: A total of 9200 patients including, 7003 (76.1%) female and 2197 (23.9%) male, were participated. About 19% of patients reported a family history of MS; the order from highest to lowest FMS prevalence was as follows: Fars (26.5%), Chaharmahal and Bakhtiari (21.1%), Tehran (20.5%), Isfahan (20.3%), Mazandaran (18.0%), and Kermanshah (12.5%). Of all FMS cases, 74.7% (1308 cases) were female and 25.3% (442 cases) were male. FMS occurrence was much more common in females than males (P-value = 0.001). Further, the mean age at onset was 30 years among FMS cases. A substantially higher probability of relapsing-remitting MS and secondary-progressive MS was found among FMS cases than sporadic MS (SMS) (P_value = 0.001). There was no significant difference in Expanded Disability Status Scale (EDSS) scores between FMS and SMS. The majority of FMS cases were observed among first-degree relatives, with the highest rate in siblings. There was a significant association between MS risk and positive familial history in both maternal and paternal aunt/uncle (P_value = 0.043 and P_value = 0.019, respectively). Multiple sclerosis occurrence among offspring of females was higher than males (P_value = 0.027). CONCLUSIONS: In summary, our findings imply a noteworthy upward trend of FMS in Iran, even more than the global prevalence, which suggests a unique Atlas of FMS prevalence in this multi-ethnic population. Despite the highest rate of FMS within Persian and Lor ethnicities, no statistically significant difference was observed among the provinces.

Atopic dermatitis: molecular, cellular, and clinical aspects.

Atopic dermatitis (AD) is a complicated, inflammatory skin disease, which numerous genetic and environmental factors play roles in its development. AD is categorized into different phenotypes and stages, although they are mostly similar in their pathophysiological aspects. Immune response alterations and structural distortions of the skin-barrier layer are evident in AD patients. Genetic makeup, lifestyle, and environment are also significantly involved in contextual factors. Genes involved in AD-susceptibility, including filaggrin and natural moisturizing, cause considerable structural modifications in the skin's lipid bilayer and cornified envelope. Additionally, the skin's decreased integrity and altered structure are accompanied by biochemical changes in the normal skin microflora's dysbiosis. The dynamic immunological responses, genetic susceptibilities, and structural modifications associated with AD's pathophysiology will be extensively discussed in this review, each according to the latest achievements and findings.

Exome sequencing reveals novel rare variants in Iranian familial multiple sclerosis: The importance of POLD2 in the disease pathogenesis.

The prevalence of familial multiple sclerosis (FMS) is increasing worldwide which endorses the heritability of the disease. Given that many genome variations are ethnicity-specific and consanguineous marriage could affect genetic diseases, hereditary disease gene analysis among FMS patients from Iran, a country with high rates of parental consanguinity, could be highly effective in finding mutations underlying disease pathogenesis. To examine rare genetic mutations, we selected three Iranian FMS cases with ≥3 MS patients in more than one generation and performed whole exome sequencing. We identified a homozygous rare missense variant in POLD2 (p. Arg141Cys; rs372336011). Molecular dynamics analysis showed reduced polar dehydration energy and conformational changes in POLD2 mutant. Further, we found a heterozygote rare missense variant in NBFP1 (p. Gly487Asp; rs778806175). Our study revealed the possible role of novel rare variants in FMS. Molecular dynamic simulation provided the initial evidence of the structural changes behind POLD2 mutant.

Association of energy adjusts nutrient-rich foods on mental health among obese and overweight women: a cross-sectional study.

PURPOSE: Mental health and obesity have a bilateral relationship with each other. No study has been done on the association between mental health and the ENRF9.3 index so far. Therefore, for the first time, the present study investigated the relationship between the ENRF9.3 index and mental health in overweight and obese women. METHODS: In the current cross-sectional study, 124 overweight and obese women were selected. Food intakes in the last year were collected with 147 items semi-quantitative food frequency questionnaire. Then, the ENRF9.3 index score was calculated for all individuals. Mental health was assessed with 21-item Depression Anxiety Stress Scales (DASS) questionnaire. RESULTS: In the present study, the total DASS score was marginally significant (P = 0.05), however, after the adjustment, it became insignificant (P > 0.05). After adjusting confounders stress also became significant (P = 0.04). No significant relationship was observed between depression and anxiety, even after adjustment (P > 0.05). CONCLUSION: The present study showed that a nutritious diet is not associated with overall mental health score, among subgroups of the DASS total score. The relationship was seen only for the stress subgroup. LEVEL OF EVIDENCE: Level III: Evidence obtained from cohort or case-control analytic studies.

Proposed minimal essential co-expression and physical interaction networks involved in the development of cognition impairment in human mid and late life.

AIM: The aim of this study was to identify the minimal essential co-expression and physical interaction networks involved in the development of cognition impairment in human mid and late life. METHODS: We searched the Online Mendelian Inheritance in Man (OMIM) database to extract the validated human genes annotated (until March 2020) for five major disorders of pathophysiological overlap and sequential chronological occurrence in human, including multiple sclerosis, type 2 diabetes mellitus, Alzheimer's disease, vascular dementia, and Lewy body dementia. Gene co-expression and physical interaction networks were subsequently constructed for the overlapping genes across the selected disorders. RESULTS: Remarkably, each of the gene co-expression and physical interaction networks consisted of single clusters (P = 0.0005 and P = 1 × 10-16, respectively). APP was the major hub in the integrated and tissue-specific co-expression networks, whereas insulin was the major hub in the physical interaction network. Several other hubs were identified across the identified networks, including TNF, VEGFA, GAPDH, and NOTCH1. CONCLUSION: We propose the minimal co-expression and physical interaction networks and their single clustering in the development of cognition impairment in human mid and late life. This is a pilot study, warranting identification of more risk genes, using additional validated databases in the future.

The Effects of Synbiotic Supplementation on Antioxidant Capacity and Arm Volumes in Survivors of Breast Cancer-Related Lymphedema.

Background and Aims: Synbiotics found to be beneficial in breast cancer survivors (BCSs) through its antioxidant properties. The aim of this study was to assess the effects of synbiotic supplementation on edema volume and some oxidative markers among obese and overweight patients with BCRL.Method: This randomized double-blind, placebo-controlled trial was conducted on 88 overweight and obese BCSs aged 18-65 years. All the subjects were given a specified low-calorie diet (LCD) and were randomly assigned into two groups to intake 109 CFU/day synbiotic supplement (n = 44) or placebo (n = 44) for 10 wk. Edema volume and serum total antioxidant capacity (TAC), malondialdehyde (MDA), glutathione peroxidase (GPx), and superoxide dismutase (SOD) concentration were measured at baseline and after the 10-wk intervention.Results: Ten-wk supplementation with synbiotics leads to a significant reduction in serum MDA levels (P = 0.001) and an increase in serum SOD concentration (P = 0.007) compared to placebo. No significant changes were observed in serum GPx, TAC, and edema volume between groups.Conclusion: Our findings reveal that 10-wk synbiotic supplementation along with a LCD program-reduced serum MDA levels and elevate the activity of SOD in overweight and obese patients with BCRL. However, its effect on serum GPx, TAC, and edema volume was not significant.

Decreased serum levels of interleukin-17, interleukin-23, TGF-ß in pemphigus vulgaris patients, and their association with disease phase.

The exact pathogenesis of Pemphigus Vulgaris (PV) has remained unclear, but it seems that cytokines play critical roles in this disease. This study aims to assess the serum levels of interleukin (IL)-6, IL-17, IL-23, and TGF-ß in PV patients and compare the results to the healthy controls. Serum levels of IL6, IL-17, IL-23, and TGF-ß were successfully determined by enzyme-linked immunosorbent assay (ELISA) in 27 newly diagnosed PV, 32 patients in remission, and 29 healthy controls. It was shown that the mean serum levels of IL-17, IL-23, and TGF-ß serum are significantly different among the PV patients and healthy controls (P values: <.001, .001, and .003, respectively). It was found that new PV patients have lower serum levels of IL-17, IL-23, and TGF-ß as compared to healthy controls (P values: <.001, <.001, and .003, respectively). Regarding IL-6, no significant difference was observed between the healthy controls and the other two groups of patients. IL-17, IL-23, and TGF-ß are involved in the pathogenesis of PV. However, more studies are required to clarify their exact roles in the immunopathogenesis of PV.

First azole-resistant Aspergillus fumigatus isolates with the environmental TR46 /Y121F/T289A mutation in Iran.

BACKGROUND: Azole resistance in Aspergillus fumigatus is an emerging problem and reported from all continents. As triazole antifungals are the mainstay of therapy in the management of invasive aspergillosis, azole-resistant A fumigatus has become a major medical concern and with complicated clinical management. OBJECTIVE: Screening of environmental presence of azole-resistant A fumigatus in Iran. METHODS: Compost from Northern Iran, collected between 2017 and 2018, was screened for the presence of azole-resistant A fumigatus with azole-containing agar. Phenotypic MICs were obtained from selected, molecularly confirmed isolates. cyp51A gene sequencing and genotyping of azole-resistant isolates were done. RESULTS: Among 300 compost samples, three A fumigatus isolates had high voriconazole MICs (≥16 mg/L) and harboured the TR46 /Y121F/T289A mutation in the cyp51A gene. Microsatellite typing of these isolates showed that two strains had the same allele across all nine examined microsatellite loci and were genotypically related to Indian azole-resistant strains. The other isolate had a different genotype. CONCLUSION: This is the first report of A fumigatus with TR46 /Y121F/T289A mutation from the region. Monitoring and surveillance of antifungal susceptibility of clinical A fumigatus is warranted in Iran and elsewhere in the region.

Factors behind ethical dilemmas regarding physical restraint for critical care nurses.

BACKGROUND: Physical restraint is among the commonly used methods for ensuring patient safety in intensive care units. However, nurses usually experience ethical dilemmas over using physical restraint because they need to weigh patient autonomy against patient safety. AIM: The aim of this study was to explore factors behind ethical dilemmas for critical care nurses over using physical restraint for patients. DESIGN: This is a qualitative study using conventional content analysis approach, as suggested by Graneheim and Lundman, to analyze the data. METHODS: Seventeen critical care nurses were purposefully recruited from the four intensive care units in Tehran, Iran. Data were collected through in-depth semi-structured interviews and were concurrently analyzed through conventional content analysis as suggested by Graneheim and Lundman. ETHICAL CONSIDERATION: This study was approved by the Ethics Committee of Iran University of Medical Sciences, Tehran, Iran with the code: IR.IUMS.REC.1397.795. Before interviews, participants were provided with explanations about the aim of the study, the confidentiality of the data, their freedom to participate, and the right to withdraw the study, and their free access to the study findings. Finally, their consents were obtained, and interviews were started. RESULTS: Factors behind ethical dilemmas for critical care nurses over using physical restraint were categorized into three main categories, namely the outcomes of using physical restraint, the outcomes of not using physical restraint, and emotional distress for nurses. The outcomes of using physical restraint were categorized into the three subcategories of ensuring patient safety, physical damage to patients, and mental damage to the patient. The outcomes of not using physical restraint fell into two subcategories, namely the risks associated with not using physical restraint and legal problems for nurses. Finally, the two subcategories of the emotional distress for nurses main category were nurses' negative feelings about restraint use and uncertainty over the decision on physical restraint use. CONCLUSION: Decision-making for restraint use is often associated with ethical dilemmas, because nurses need to weight the outcomes of its use against the outcomes of not using it and also consider patient safety and autonomy. Health authorities are recommended to develop clear evidence-based guidelines for restraint use and develop and implement educational and counseling programs for nurses on the principles of ethical nursing practice, patient rights, physical restraint guidelines and protocols, and management of emotional, ethical, and legal problems associated with physical restraint use.