Single-cell spatial landscapes of the lung tumour immune microenvironment.

Single-cell technologies have revealed the complexity of the tumour immune microenvironment with unparalleled resolution1-9. Most clinical strategies rely on histopathological stratification of tumour subtypes, yet the spatial context of single-cell phenotypes within these stratified subgroups is poorly understood. Here we apply imaging mass cytometry to characterize the tumour and immunological landscape of samples from 416 patients with lung adenocarcinoma across five histological patterns. We resolve more than 1.6 million cells, enabling spatial analysis of immune lineages and activation states with distinct clinical correlates, including survival. Using deep learning, we can predict with high accuracy those patients who will progress after surgery using a single 1-mm2 tumour core, which could be informative for clinical management following surgical resection. Our dataset represents a valuable resource for the non-small cell lung cancer research community and exemplifies the utility of spatial resolution within single-cell analyses. This study also highlights how artificial intelligence can improve our understanding of microenvironmental features that underlie cancer progression and may influence future clinical practice.

Single-cell spatial immune landscapes of primary and metastatic brain tumours.

Single-cell technologies have enabled the characterization of the tumour microenvironment at unprecedented depth and have revealed vast cellular diversity among tumour cells and their niche. Anti-tumour immunity relies on cell-cell relationships within the tumour microenvironment1,2, yet many single-cell studies lack spatial context and rely on dissociated tissues3. Here we applied imaging mass cytometry to characterize the immunological landscape of 139 high-grade glioma and 46 brain metastasis tumours from patients. Single-cell analysis of more than 1.1 million cells across 389 high-dimensional histopathology images enabled the spatial resolution of immune lineages and activation states, revealing differences in immune landscapes between primary tumours and brain metastases from diverse solid cancers. These analyses revealed cellular neighbourhoods associated with survival in patients with glioblastoma, which we leveraged to identify a unique population of myeloperoxidase (MPO)-positive macrophages associated with long-term survival. Our findings provide insight into the biology of primary and metastatic brain tumours, reinforcing the value of integrating spatial resolution to single-cell datasets to dissect the microenvironmental contexture of cancer.

The association between adherence to unhealthy plant-based diet and risk of COVID-19: a cross-sectional study.

BACKGROUND: The fast spread of the coronavirus disease 2019 (COVID-19) epidemic and its high mortality were quickly considered by the health community. Dietary patterns play an important role in strengthening or weakening the immune system and thus incidence of diseases. AIM: The present study can provide a comprehensive picture of the association between adherence to unhealthy plant-based diet (uPDI) and COVID-19 incidence. METHODS: This study was undertaken on 8157 adults' participants of the Yazd Health Study (YaHS) and Taghzieh Mardom-e-Yazd (TAMIZ) study aged 20 to 70 years. Data on dietary intakes were obtained using a validated food frequency questionnaire (FFQ). Multivariable logistic regression analysis was used to assess the association between uPDI and COVID-19. RESULTS: We found a significant association between uPDI and the risk of COVID-19 (OR: 1.36; 95% CI: 1.05-1.75) in the crude model. After adjusting potential confounders, a significant increasing trend in the odds of COVID-19 across increasing quintiles of uPDI (OR: 1.58;95% CI: 1.05-2.37; P-value: 0.027) was observed. Stratified analysis based on sex indicated that uPDI significantly increased the risk of COVID-19 only in males (OR: 1.73;95% CI: 1.12-2.67; P-value: 0.012) and had no effect on females. CONCLUSIONS: Participants in the highest quintiles of the uPDI had 58% higher odds of COVID-19 compared to subjects in the lowest quintile of uPDI. Although our study has promising results, stronger clinical studies are needed.

Porphysome Engineered With Specific Protein Binding Sites as a Multimodal Theranostic Nanocarrier for Targeted Protein Delivery.

The immobilization of proteins on the surface of carriers is challenging due to the loss of protein structure and function in this process. Here, we report the development of the protein immobilization on the surface of the metallated-porphyrin complex in the porphysome nanocarrier. The conjugated Ni-porphyrin to fatty acid (as a tail) has been synthesized and independently placed at the depth of the bilayer center of Dipalmitoylphosphatidylcholine (DPPC) in which the Ni-porphyrin was at the polar region of the membrane and is thus superficial. This porphysome (DPPC: Ni-porphyrin, 4 : 1 mole ratio) was formed by supramolecular self-assembly with a diameter of 173±7 nm and zeta potential -8.5±3.4 mv, which exhibited no significant toxicity at the experimental concentrations and acceptable cellular uptake on MCF-7 cells. The physicochemical properties and specific protein binding sites of the firefly luciferase as a model protein into the porphysome (1 : 2 mole ratio) show the conjugation efficiency about 80 % and the conformation of protein was completely maintained. Furthermore, bioluminescence assay and SDS-PAGE confirmed the preservation of protein function. The stabilized platform of porphyrin-lipid structure can potentially improve the efficacy of protein functionality for a particular display, shifting porphysomes from a simple carrier to a therapeutic agent.

Agent-Based Modelling Reveals the Role of the Tumor Microenvironment on the Short-Term Success of Combination Temozolomide/Immune Checkpoint Blockade to Treat Glioblastoma.

Glioblastoma is the most common and deadly primary brain tumor in adults. All glioblastoma patients receiving standard-of-care surgery-radiotherapy-chemotherapy (i.e., temozolomide (TMZ)) recur, with an average survival time of only 15 months. New approaches to the treatment of glioblastoma, including immune checkpoint blockade and oncolytic viruses, offer the possibility of improving glioblastoma outcomes and have as such been under intense study. Unfortunately, these treatment modalities have thus far failed to achieve approval. Recently, in an attempt to bolster efficacy and improve patient outcomes, regimens combining chemotherapy and immune checkpoint inhibitors have been tested in trials. Unfortunately, these efforts have not resulted in significant increases to patient survival. To better understand the various factors impacting treatment outcomes of combined TMZ and immune checkpoint blockade, we developed a systems-level, computational model that describes the interplay between glioblastoma, immune, and stromal cells with this combination treatment. Initializing our model to spatial resection patient samples labeled using imaging mass cytometry, our model's predictions show how the localization of glioblastoma cells, influence therapeutic success. We further validated these predictions in samples of brain metastases from patients given they generally respond better to checkpoint blockade compared with primary glioblastoma. Ultimately, our model provides novel insights into the mechanisms of therapeutic success of immune checkpoint inhibitors in brain tumors and delineates strategies to translate combination immunotherapy regimens more effectively into the clinic. SIGNIFICANCE STATEMENT: Extending survival times for glioblastoma patients remains a critical challenge. Although immunotherapies in combination with chemotherapy hold promise, clinical trials have not shown much success. Here, systems models calibrated to and validated against patient samples can improve preclinical and clinical studies by shedding light on the factors distinguishing responses/failures. By initializing our model with imaging mass cytometry visualization of patient samples, we elucidate how factors such as localization of glioblastoma cells and CD8+ T cell infiltration impact treatment outcomes.

Insights into the potential for mutualistic and harmful host-microbe interactions affecting brown alga freshwater acclimation.

Microbes can modify their hosts' stress tolerance, thus potentially enhancing their ecological range. An example of such interactions is Ectocarpus subulatus, one of the few freshwater-tolerant brown algae. This tolerance is partially due to its (un)cultivated microbiome. We investigated this phenomenon by modifying the microbiome of laboratory-grown E. subulatus using mild antibiotic treatments, which affected its ability to grow in low salinity. Low salinity acclimation of these algal-bacterial associations was then compared. Salinity significantly impacted bacterial and viral gene expression, albeit in different ways across algal-bacterial communities. In contrast, gene expression of the host and metabolite profiles were affected almost exclusively in the freshwater-intolerant algal-bacterial communities. We found no evidence of bacterial protein production that would directly improve algal stress tolerance. However, vitamin K synthesis is one possible bacterial service missing specifically in freshwater-intolerant cultures in low salinity. In this condition, we also observed a relative increase in bacterial transcriptomic activity and the induction of microbial genes involved in the biosynthesis of the autoinducer AI-1, a quorum-sensing regulator. This could have resulted in dysbiosis by causing a shift in bacterial behaviour in the intolerant algal-bacterial community. Together, these results provide two promising hypotheses to be examined by future targeted experiments. Although they apply only to the specific study system, they offer an example of how bacteria may impact their host's stress response.

Associations between adherence to Mediterranean dietary pattern and frequency, duration, and severity of migraine headache: A cross-sectional study.

BACKGROUND: The present study was conducted to explore the association between adherence to Mediterranean dietary pattern and migraine headache features including frequency, duration, and severity, as well as patients' migraine-related disabilities among the Iranian population diagnosed with migraine. METHODS: In the present cross-sectional study on 262 migraine patients aged 20-50 years old, a validated 168-item, food frequency questionnaire was used to assess the dietary intakes of participants. The Mediterranean diet score was calculated for each subject using nine pre-defined dietary components and ranged from 0-9. The headache severity, duration, frequency, migraine headache index score (MHIS), and headache impact test-6 (HIT-6) were measured using related questionnaires. RESULTS: After controlling for potential confounders, Mediterranean diet tended to be associated with lower headache frequency (ß = -1.74, 95% CI: -3.53,0.03) and duration (ß = -0.28, 95% CI: -0.59, -0.02) and was significantly associated with lower MHIS (ß = -29.32, 95% CI: -51.22, -7.42), and HIT-6 score (ß = -2.86, 95% CI: -5.40, -0.32) for those in the highest category of Mediterranean diet scores compared to the lowest category. A subgroup analysis of women also revealed a negative association between Mediterranean diet and headaches frequency (ß = -2.30, 95% CI: -4.27, -0.32), duration (ß = -0.42, 95% CI: -0.78, -0.07), scores of MHIS (ß = -47.44, 95% CI: -71.90, -22.99), and HIT-6 (ß = -3.45, 95% CI: -6.29, -0.61), after controlling for potential confounders. CONCLUSIONS: The present study suggests that adherence to the Mediterranean dietary pattern is associated with lower headache frequency, duration, MHIS, and HIT-6 score.

Associations between diet quality and migraine headaches: a cross-sectional study.

AIMS: We evaluated associations between diet quality and migraine outcomes. METHODS: The current work represented a cross-sectional study on 262 patients with migraine (20-50 y). Diet quality was assessed using the standard healthy eating index 2015 (HEI-2015) and alternative healthy eating index 2010 (AHEI-2010). A validated 168-item food frequency questionnaire was used to assess dietary intake. Migraine outcomes included clinical factors (severity, duration, frequency, and disability related to migraine) and serum nitric oxide (NO). Associations between diet quality indices and migraine outcomes were evaluated using linear regressions, and ß and 95% corresponding confidence interval (CI) were reported. RESULTS: HEI-2015 was inversely associated with migraine frequency (ß = -4.75, 95% CI: -6.73, -2.76) in patients with the highest HEI scores (third tertile) vs. those with the lowest scores (first tertile) after adjusting for relevant confounders. AHEI-2010 was inversely associated with migraine frequency (ß = -3.67, 95% CI: -5.65, -1.69) and migraine-related disability (ß = -2.74, 95% CI: -4.79, -0.68) in adjusted models. Also, AHEI-2010 was inversely associated with migraine severity in patients in the second vs. first tertile (ß = -0.56; 95% CI: -1.08, -0.05). We detected no associations between diet quality and NO levels (All P > 0.14). CONCLUSIONS: Improved diet quality may be associated with favorable migraine outcomes (lower headache frequency, severity, and migraine-related disability). Future studies are required to confirm and delineate the causal mechanisms of our observations.

The effect of cinnamon consumption on lipid profile, oxidative stress, and inflammation biomarkers in adults: An umbrella meta-analysis of randomized controlled trials.

AIMS: Cinnamon is a polyphenol-rich spice that has beneficial effects on markers of cardio metabolic health such as lipid profile, oxidative stress, and inflammation. Despite the accumulating evidence from meta-analyses on the effects of cinnamon on these markers, their findings are controversial. Thus, this umbrella meta-analysis was performed to evaluate the present evidence and provide a conclusive clarification. DATA SYNTHESIS: We searched the following international databases from inception to January 2022: PubMed, Scopus, Web of Science and Embase, and Google Scholar. Our findings of eleven meta-analyses showed that cinnamon consumption can significantly improve total cholesterol (TC) (WMD = -1.01 mg/dL; 95% CI: -2.02, -0.00, p = 0.049), low-density lipoprotein-cholesterol (LDL-C) (WMD = -0.82 mg/dL; 95% CI: -1.57, -0.07, p = 0.032), and high-density lipoprotein-cholesterol (HDL-C) (WMD = 0.47 mg/dL; 95% CI: 0.17, 0.77, p = 0.002) levels but not triglyceride (TG) levels (WMD = -0.13 mg/dL; 95% CI: -0.58, 0.32, p = 0.570). Our results did not show any significant effect of cinnamon on malondialdehyde (MDA) levels (WMD = -0.47; 95% CI: -0.99, 0.05, p = 0.078) and C-reactive protein (CRP) levels (WMD = -1.33; 95% CI: -2.66, 0.00, p = 0.051) but there was enhanced total antioxidant capacity (TAC) in patients with type 2 diabetes (T2DM) and polycystic ovary syndrome (PCOS) (WMD = 0.34; 95% CI: 0.04, 0.64, p = 0.026) and increased levels of interleukin-6 (WMD = -1.48; 95% CI: -2.96, -0.01, p = 0.049). CONCLUSIONS: Our results support the usefulness of cinnamon intake in modulating an imbalanced lipid profile in some metabolic disorders, particularly PCOS, as well as in improving TAC and interleukin-6. The review protocol was registered on PROSPERO as CRD42022358827.

The influential role of parents' socioeconomic status and diet quality on their children's dietary behavior: results from the LIPOKAP study among the Iranian population.

PURPOSE: There is a paucity of evidence regarding the influential factors on Iranian children's diet quality. To assess this issue, we explore the relationship between parental diet quality, socioeconomic status (SES), and nutritional knowledge with their children's diet quality using a cross-sectional sample of the Iranian population. METHODS: In this study, paired parents along with one of their children (aged 6-18 years old) who lived with them were included. Dietary intake was assessed using a food frequency questionnaire (FFQ) and diet quality was determined using an Alternative Healthy Eating Index-2010 (AHEI). Nutritional knowledge and SES were also explored using validated questionnaires. Multiple linear regression analysis was used and beta (ß) and corresponding 95% confidence interval (CI) were reported. RESULTS: After controlling for potential confounders, the parents' AHEI was significantly associated with their children's diet quality (ß = 12.34, 95% CI: 10.75, 13.93; P < 0.001). The nutritional knowledge of parents was significantly associated with children's AHEI after controlling for potential confounders (ß = 1.63, 95% CI: 0.14, 3.11; P = 0.032). Moreover, the parents' SES was inversely associated with the AHEI of children (ß=-3.76, 95% CI: -5.40, -2.11; P < 0.001); however, further adjustment for confounders attenuated this relationship (Model 3: ß = 0.87, 95% CI: -0.76, 2.34; P = 0.269). CONCLUSIONS: We found that the children's diet quality could be influenced by their parents' SES, nutritional knowledge, and diet quality. Our findings suggest that improving the nutritional knowledge of parents not only may improve the healthy eating pattern of parents but also could influence their children's diet quality.

Peptide mediated targeted delivery of gold nanoparticles into the demyelination site ameliorates myelin impairment and gliosis.

Drug development for multiple sclerosis (MS) clinical management focuses on both neuroprotection and repair strategies, and is challenging due to low permeability of the blood-brain barrier, off-target distribution, and the need for high doses of drugs. The changes in the extracellular matrix have been documented in MS patients. It has been shown that the expression of nidogen-1 increases in MS lesions. Laminin forms a stable complex with nidogen-1 through a heptapeptide which was selected to target the lesion area in this study. Here we showed that the peptide binding was specific to the injured area following lysophosphatidylcholine (LPC) induced demyelination. In vivo data showed enhanced delivery of the peptide-functionalized gold nanoparticles (Pep-GNPs) to the lesion area. In addition, Pep-GNPs administration significantly enhanced myelin content and reduced astrocyte/microglia activation. Results demonstrated the possibility of using this peptide to target and treat lesions in patients suffering from MS.

LncRNA-miRNA network analysis across the Th17 cell line reveals biomarker potency of lncRNA NEAT1 and KCNQ1OT1 in multiple sclerosis.

Differentiation of CD4+ T cells into Th17 cells is an important factor in the onset and progression of multiple sclerosis (MS) and Th17/Treg imbalance. Little is known about the role of lncRNAs in the differentiation of CD4+ cells from Th17 cells. This study aimed to analyse the lncRNA-miRNAs network involved in MS disease and its role in the differentiation of Th17 cells. The lncRNAs in Th17 differentiation were obtained from GSE66261 using the GEO datasets. Differential expression of lncRNAs in Th17 primary cells compared to Th17 effector cells was investigated by RNA-seq analysis. Next, the most highlighted lncRNAs in autoimmune diseases were downloaded from the lncRNAs disease database, and the most critical miRNA was extracted by literature search. Then, the lncRNA-miRNA interaction was achieved by the Starbase database, and the ceRNA network was designed by Cytoscape. Finally, using the CytoHubba application, two hub lncRNAs with the most interactions with miRNAs were identified by the MCODE plug-in. The expression level of genes was measured by qPCR, and the plasma level of cytokines was analysed by ELISA kits. The results showed an increase in the expression of NEAT1, KCNQ1OT1 and RORC and a decrease in the expression of FOXP3. In plasma, an upregulation of IL17 and a downregulation of TGFB inflammatory cytokines were detected. The dysregulated expression of these genes could be attributed to relapsing-remitting MS (RR-MS) patients and help us understand MS pathogenesis better.

The effects of the dietary approaches to stop hypertension (DASH) diet on oxidative stress and clinical indices of migraine patients: a randomized controlled trial.

AIMS: The relationship between the Dietary Approaches to Stop Hypertension (DASH) diet and oxidative stress (OS) in patients diagnosed with migraine is unknown and remains to be examined. Hence, we conducted a parallel-group, randomized controlled trial to investigate this issue. METHODS: Of the 102 women who met all the inclusion criteria, 51 individuals were randomized to the DASH diet group and 51 to the usual dietary advice group to receive allocated intervention for three months. In order to assess the compliance of participants to the DASH diet, dietary records, and serum vitamin C levels were examined. Parameters of OS status (e.g. nitric oxide (NO), total antioxidant capacity (TAC), total oxidative status (TOS), malondialdehyde (MDA), and oxidative stress index (OSI)) and clinical indices of migraine (e.g. migraine index (MI), headache dairy result (HDR), and migraine headache index score (MHIS)) were assessed at the beginning and the end of the study. RESULTS: There was a significant reduction in NO (-5.75 vs. + 4.18, P = 0.025) and TOS (-1.55 vs. + 0.71, P = 0.034), and a marginally significant reduction in OSI (-0.10 vs. + 0.14, P = 0.060) in the DASH group compared with the control. Compliance with the DASH diet resulted in a significant decrease in the score of MI (-31.33 vs. - 15.09), HDR (-5.04 vs. -2.51), and MHIS (-44.21 vs. -26.74). Moreover, no significant change was observed in TAC, MDA, and total thiol content. CONCLUSION: This type of dietary approach can be considered as a complementary treatment for migraine patients, also further investigations are needed to replicate our findings.Trial registration: Iranian Registry of Clinical Trials identifier: IRCT20121216011763N38.

Food groups and nutrients consumption and risk of endometriosis: a systematic review and meta-analysis of observational studies.

Dietary factors may play a role in the etiology of endometriosis and dietary intake of some food groups and nutrients could be associated with endometriosis risk. This systematic review and meta-analysis of observational studies was conducted to summarize the findings on the association between dietary intakes of selected food groups and nutrients (dairy, fats, fruits, vegetables, legumes, and animal-derived protein sources), and the risk of endometriosis among adult women. PubMed, Scopus, and ISI Web of Science were systematically searched up to September 2022. The inverse variance-weighted fixed-effect method was used to estimate the effect size and corresponding 95% CI. A total of 8 publications (4 studies) including 5 cohorts and 3 case-control with a sample size ranging from 156 to 116,607 were included in this study. A higher intake of total dairy [all low-fat and high-fat dairy foods] was associated with decreased risk of endometriosis (RR 0.90; 95% CI, 0.85 to 0.95; P < 0.001; I2 = 37.0%), but these associations were not observed with intakes of low or high-fat dairy, cheese or milk. Increased risk of endometriosis was associated with higher consumption of red meat (RR 1.17; 95% CI, 1.08 to 1.26; P < 0.001; I2 = 82.4%), trans fatty acids (TFA) (RR 1.12; 95% CI, 1.02 to 1.23; P = 0.019; I2 = 73.0%), and saturated fatty acids (SFA) (RR 1.06; 95% CI, 1.04 to 1.09; P < 0.001; I2 = 57.3%). The results of this meta-analysis suggest that there may be differing associations between dietary intake of dairy foods, red meat, SFAs, and TFAs and the risk of endometriosis. It may be useful to extend the analysis to other types of food groups and dietary patterns to obtain a complete picture. Additionally, further investigations are needed to clarify the role of diet in the incidence and progression of endometriosis.Trial registration: PROSPERO, CRD42020203939.

SARS-CoV-2: phenotype, genotype, and characterization of different variants.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of coronavirus disease 2019 (COVID-19), a major international public health concern. Because of very similar amino acid sequences of the seven domain names, SARS-CoV-2 belongs to the Coronavirinae subfamily of the family Coronaviridae, order Nidovirales, and realm Riboviria, placed in exceptional clusters, but categorized as a SARS-like species. As the RNA virus family with the longest genome, the Coronaviridae genome consists of a single strand of positive RNA (25-32 kb in length). Four major structural proteins of this genome include the spike (S), membrane (M), envelope (E), and the nucleocapsid (N) protein, all of which are encoded within the 3' end of the genome. By engaging with its receptor, angiotensin-converting enzyme 2 (ACE2), SARS-CoV-2 infects host cells. According to the most recent epidemiological data, as the illness spread globally, several genetic variations of SARS-CoV-2 appeared quickly, with the World Health Organization (WHO) naming 11 of them. Among these, seven SARS-CoV-2 subtypes have received the most attention. Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), Delta (B.1.617.2), and Omicron (B.1.617.2) are now designated as variations of concern (VOC) (B.1.1.529). Lambda (C.37) and Mu are variations of interest (VOI) (B.1.621). The remaining six are either being monitored or are no longer considered a threat. On the basis of studies done so far, antiviral drugs, antibiotics, glucocorticoids, recombinant intravenous immunoglobulin, plasma therapy, and IFN-α2b have been used to treat patients. Moreover, full vaccination is associated with lower infection and helps prevent transmission, but the risk of infection cannot be eliminated completely in vaccinated people.

Effects of greater occipital nerve block with local anesthetic and triamcinolone for treatment of medication overuse headache: an open-label, parallel, randomized, controlled clinical trial.

AIM: There is a paucity of evidence and consensus on exactly how to carry out the detoxification process. To examine the effect of a greater occipital nerve block (GONB) in the detoxification process, we conducted an open-label, parallel, randomized, controlled clinical trial. MATERIALS AND METHODS: In order to conduct this study, 54 medication-overuse headache (MOH) patients were recruited and allocated randomly to group A (n = 27) or B (n = 27). In both groups, patients underwent detoxification processes without any acute migraine medication or analgesics. During the run-in period, all patients in both groups received the same education, managed by a neurologist and nutritionist. All patients were offered maximally 300 mL of promethazine syrup (5 mg/5 mL) to be taken 10 mg every 8 h during the first 10 days of the study. A 2-mL syringe containing 1 mL of lidocaine 2% and 1 mL of triamcinolone 40 mg/mL was prepared for each patient of group A for conducting GONB. Characteristics of headache attacks, including headache severity, frequency, and duration, were assessed at baseline and after 3 months of intervention. RESULTS: Twenty-six patients in group A (96.3%) and twenty-three in group B (85.2%) completed detoxification, and were thus cured of MOH (P = 0.351). The present study revealed that GONB with local anesthetic and triamcinolone significantly improved the characteristics of headache, including frequency (- 13.66 in group A and - 7.55 in group B), duration (- 7.92 in group A and - 5.88 in group B), and severity (- 3.44 in group A vs. - 1.33 in group B) in group A compared to control (all P value < 0.05). CONCLUSIONS: Although both detoxification programs were effective, detoxification with GONB resulted in better outcomes. TRIAL REGISTRATION: Iranian Registry of Clinical Trials (registration number; IRCT20150906023922N2).

The Effect of Saffron (Crocus sativus L.) Supplementation on Renal Function: A Systematic Review and Meta-Analysis of Randomized Controlled Clinical Trials.

Background: The present systematic review and meta-analysis of randomized controlled trials (RCTs) aimed at determining the effect of saffron supplementation on renal function. Methods: Electronic databases were searched up to February 2021. The risk of bias in individual studies was assessed using the Cochrane Collaboration tool. The overall weighted mean difference (WMD) and their 95% confidence intervals (CIs) were calculated using random-effect models. P < 0.05 was considered statistically significant. Results: A total of 11 trials were included in this study. Saffron had beneficial effect on BUN (WMD = -0.69 mg/dl; 95% CI, -1.36 to -0.01; P=0.046) compared to placebo, with significant heterogeneity (I 2 = 49.6%, P=0.037). However, it had no significant effect on serum Cr (WMD = 0.04 mg/dl; 95% CI: -0.01 to 0.09; P=0.127). Conclusion: It seems that saffron supplementation had no significant effect on Cr as a renal function factor. However, BUN reduction was significant in the saffron group compared to placebo.

A comparison of the effects of teaching through simulation and the traditional method on nursing students' self-efficacy skills and clinical performance: a quasi-experimental study.

INTRODUCTION: Simulators in a clinical environment provide a space where students can acquire skills and experience under the supervision of their professors without any worries or inflicting any harm on their patients. The current study aimed to compare the effects of teaching through simulation and the traditional method on nursing students' self-efficacy skills and clinical performance. METHOD: The current study was quasi-experimental and adopted a pre-test & post-test design. The population consisted of 122 students of nursing, out of whom 100 students were selected as the sample. Then, they were randomly divided into an experimental and a control group. A questionnaire assessed the students' self-efficacy skills and clinical performance before and after implementing the instructional programs. The data were analyzed using descriptive and inferential statistical techniques in SPSS 23. FINDINGS: The mean of the participants' self-efficacy scores increased significantly after the intervention (from 87.57 to 142.13). Moreover, the mean of the participants' clinical performance increased significantly after the intervention (from 2.16 to 4.57). The findings indicated that simulation teaching significantly affects nursing students' self-efficacy and clinical performance. CONCLUSION: Simulation was recommended as an effective teaching methodology, particularly in nurses' internship wards. In other words, acquiring the essential skills through applying the simulation method is recommended before entering real-world environments.

Interplay between SARS-CoV-2-derived miRNAs, immune system, vitamin D pathway and respiratory system.

The new coronavirus pandemic started in China in 2019. The intensity of the disease can range from mild to severe, leading to death in many cases. Despite extensive research in this area, the exact molecular nature of virus is not fully recognized; however, according to pieces of evidence, one of the mechanisms of virus pathogenesis is through the function of viral miRNAs. So, we hypothesized that SARS-CoV-2 pathogenesis may be due to targeting important genes in the host with its miRNAs, which involved in the respiratory system, immune pathways and vitamin D pathways, thus possibly contributing to disease progression and virus survival. Potential miRNA precursors and mature miRNA were predicted and confirmed based on the virus genome. The next step was to predict and identify their target genes and perform functional enrichment analysis to recognize the biological processes connected with these genes in the three pathways mentioned above through several comprehensive databases. Finally, cis-acting regulatory elements in 5' regulatory regions were analysed, and the analysis of available RNAseq data determined the expression level of genes. We revealed that thirty-nine mature miRNAs could theoretically derive from the SARS-CoV-2 genome. Functional enrichment analysis elucidated three highlighted pathways involved in SARS-CoV-2 pathogenesis: vitamin D, immune system and respiratory system. Our finding highlighted genes' involvement in three crucial molecular pathways and may help develop new therapeutic targets related to SARS-CoV-2.

The expanding role of CDR1-AS in the regulation and development of cancer and human diseases.

CircRNAs are a superabundant and highly conserved group of noncoding RNAs (ncRNAs) that are characterized by their high stability and integrity compared with linear forms of ncRNAs. Recently, their critical role in gene expression regulation has been shown; thus, it is not far-fetched to believe that their abnormal expression can be a cause of different kinds of diseases such as cancer, neurodegenerative, and autoimmune diseases. They can have a function in variety of biological processes such as microRNA (miRNA) sponging, interacting with RNA-binding proteins, or even an ability to translate to proteins. A huge challenge in finding diagnostic biomarkers is finding noninvasive biomarkers that can be detected in human fluids, especially blood samples. CircRNAs are becoming candidate biomarkers for diagnosis and prognosis of these diseases through their ability to transverse from the blood-brain barrier and their broad presence in circulating exosomes. The circRNA for miRNA-7 (ciRS-7) is newly recognized, and acknowledged to being related to human pathology and cancer progression. In this review, we first briefly summarize the latest studies about their characteristics, biogenesis, and their mechanisms of action in the regulation and development of human diseases. Finally, we provide a list of diseases that are linked to one member of this novel class of ncRNAs called ciRS-7.