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.

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.

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.

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).

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.

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.

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.

Effectiveness of a school-based health education program to improve the symptoms of premenstrual syndrome in high school girls in Ilam.

BACKGROUND: The premenstrual syndrome happens periodically and affects both the individual and family. The aim of this study was to determine the effect of the health education program on reducing premenstrual syndrome in high school girls in Ilam. MATERIALS AND METHODS: This experimental study was conducted in girls' high schools in Ilam, in 2017-2018. In total, 120 students were enrolled in the study (intervention group = 61 and control group = 59) and selected through convenience sampling. In this study, a standard Premenstrual Symptoms Screening Tool (PSST) was used to diagnose students with premenstrual syndrome or Premenstrual Dysphoric Disorder (PMDD). The educational program for the intervention group was held in four sessions of 30 min for 4 consecutive weeks. The obtained data were analyzed by the SPSS statistical software at a significance level of less than 0.05. RESULTS: The results showed a significant difference in the proportion of cases with moderate and severe PMS and PMDD between intervention and control groups in follow-up (P < 0.001). However, these proportions were not significantly different between the two groups in the baseline. CONCLUSIONS: According to the results, the educational program can be recommended as an effective intervention for girls with moderate-to-severe premenstrual symptoms and premenstrual dysphoric disorder.

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.

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.

Rewiring of miRNA-mRNA bipartite co-expression network as a novel way to understand the prostate cancer related players.

The differential expression and direct targeting of mRNA by miRNA are two main logics of the traditional approach to constructing the miRNA-mRNA network. This approach, could be led to the loss of considerable information and some challenges of direct targeting. To avoid these problems, we analyzed the rewiring network and constructed two miRNA-mRNA expression bipartite networks for both normal and primary prostate cancer tissue obtained from PRAD-TCGA. We then calculated beta-coefficient of the regression-model when miR was dependent and mRNA independent for each miR and mRNA and separately in both networks. We defined the rewired edges as a significant change in the regression coefficient between normal and cancer states. The rewired nodes through multinomial distribution were defined and network from rewired edges and nodes was analyzed and enriched. Of the 306 rewired edges, 112(37%) were new, 123(40%) were lost, 44(14%) were strengthened, and 27(9%) weakened connections were discovered. The highest centrality of 106 rewired mRNAs belonged to PGM5, BOD1L1, C1S, SEPG, TMEFF2, and CSNK2A1. The highest centrality of 68 rewired miRs belonged to miR-181d, miR-4677, miR-4662a, miR-9.3, and miR-1301. SMAD and beta-catenin binding were enriched as molecular functions. The regulation was a frequently repeated concept in the biological process. Our rewiring analysis highlighted the impact of ß-catenin and SMAD signaling as also some transcript factors like TGFB1I1 in prostate cancer progression. Altogether, we developed a miRNA-mRNA co-expression bipartite network to identify the hidden aspects of the prostate cancer mechanism, which traditional analysis -like differential expression- was not detect it.

Cloning and Recombinant Protein Expression in Lactococcus lactis.

The Lactococcus lactis, a Gram-positive bacteria, is an ideal expression host for the overproduction of heterologous proteins in a properly folded and functional form. L. lactis has been identified as an efficient cell factory, generally recognized as safe (GRAS), has a long history of safe use in food production, and is known to have probiotic properties. Key desirable features of L. lactis include the following: (1) rapid growth to high cell densities, not requiring aeration which facilitates large-scale fermentation; (2) its Gram-positive nature precludes the presence of contaminating endotoxins; (3) the capacity to secrete stable recombinant protein into the growth medium with few proteases resulting in a properly folded, full-length protein; and (4) the availability of diverse expression vectors facilitating various cloning options. We have previously described production of several recombinant proteins with varying degrees of predicted structural complexities using the L. lactis pH-dependent P170 promoter. The purpose of this chapter is to provide a detailed protocol for facilitating wider application of L. lactis as a reliable platform for expression of heterologous recombinant proteins in soluble form. Here, we present details of the various steps involved such as cloning of the target gene in appropriate expression plasmid vector, determination of the expression levels of the heterologous protein, and initial purification of the expressed soluble recombinant protein of interest.

Female high school students' knowledge and attitude toward breast cancer.

BACKGROUND: Breast cancer is the most common cancer among women. Even though early detection and diagnosis of this disease can reduce mortality considerably, several studies have shown that more than 92% of women are unaware of the risk factors for breast cancer and of breast cancer screening tests. The simultaneous promotion of screening and provision of education can increase community health and reduce medical costs, and students can play a leading role in informing and educating people in society. AIM: The present study aims to examine the level of knowledge and attitude of female students in senior high schools in Fasa regarding breast cancer screening. METHODS: In this cross-sectional study, the random sampling method was applied to survey 350 female high school students, only 311 of whom completed the study. Questionnaires were completed in girls' high schools, and the data was analyzed by SPSS Software, Version 25. RESULTS: The results revealed that more than 87% of students were unaware or had incorrect information regarding breast cancer screening. The link between the type of breast cancer information sources and students' general knowledge was significant. Most students were aware of the risk of breast cancer, but they were uninformed of its symptoms, risk factors, and prevention strategies, and students with a family history of breast cancer had a higher score in terms of mammography knowledge than students with no family history of breast cancer, although this difference was not significant (mean ± standard deviation = 0.94 ± 0.90 vs. 0.67 ± 0.81, p = 0.19). CONCLUSION: The level of awareness and attitude of Fasa high school girls regarding breast cancer and screening methods is not acceptable. Therefore, it is recommended that educational programs be implemented to increase the awareness of students in schools, so that the number of screenings increases with the institutionalization of this information. Likewise, by transferring information through students to their families, the level of awareness in the whole society will hopefully increase as well.

Expression analysis of hsa_circ_0020397, hsa_circ_0005986, hsa_circ_0003028, and hsa_circ_0006990 in renal cell carcinoma.

Renal cell carcinoma (RCC) is a prevalent heterogeneous kidney cancer. So far, different genes have been reported for RCC development. However, its particular molecular mechanism remains unclear. Circular RNAs (circRNAs), a class of non-coding RNAs, are involved in numerous biological processes in different malignancies such as RCC. This study aims to assess the expression and underlying mechanism of four circRNAs (hsa_circ_0020397, hsa_circ_0005986, hsa_circ_0003028, hsa_circ_0006990) with possible new roles in RCC. In the experimental step, we investigated the expression of these four circRNAs in our RCC samples using quantitative real-time polymerase chain reaction. In the bioinformatics step, the differential expressed mRNAs (DEmRNAs), and miRNAs (DEmiRNAs) were obtained from the GEO datasets using the GEO2R tool. A protein-protein interaction network was constructed using the STRING database, and hub genes were identified by Cytoscape. Molecular pathways associated with hub genes were detected using KEGG pathway enrichment analysis. Then, we utilized the ToppGene database to detect the relationships between DEmiRNAs and hub genes. Furthermore, interactions between circRNAs and DEmiRNAs were predicted by the StarBase and circinteractome databases. Finally, a circRNA-DEmiRNA-hub gene triple network was constructed. Our results revealed that the expression of hsa_circ_0020397, hsa_circ_0005986, and hsa_circ_0006990 was downregulated in RCC tissues. Moreover, these circRNAs had a significantly lower expression in patients with a history of kidney disease. Furthermore, hsa_circ_0003028 and hsa_circ_0006990 showed higher expression in the tumor of participants with Lymphovascular/perineural invasion and oncocytoma type, respectively. Based on bioinformatic results, 15 circRNA-DEmiRNA-hub gene ceRNA regulatory axes were predicted, which included three hub genes, five miRNAs, and four selected circRNAs. In conclusion, the current work is the first to emphasize the expression of the hsa_circ_0020397, hsa_circ_0005986, hsa_circ_0003028, and hsa_circ_0006990 in RCC patients presents a novel perspective on the molecular processes underlying the pathogenic mechanisms of RCC.

Association of Dietary Acid Load With Metabolic Syndrome and Its Components in Iranian Adults: A Cross-Sectional Study.

Introduction Metabolic syndrome (MetS) remains one of the leading health challenges worldwide. A combination of genetic and environmental factors has been implicated in the etiology of MetS. Diet is a changeable environmental risk factor, and dietary modifications could significantly reduce the incidence and mortality of numerous diseases, including MetS. Certain dietary factors may contribute to MetS by affecting the acid-base balance within the body. This study examined the association of dietary acid load (DAL) with MetS and its components in Iranian adults. Materials and methods This cross-sectional study was conducted in 2022 on 6356 Iranian adults aged 35-70 years. Potential renal acid load (PRAL) and net endogenous acid production (NEAP) as two indicators of DAL were calculated based on nutrient intake data from validated food frequency questionnaires. MetS and its components were defined according to the Adult Treatment Panel III criteria. Logistic regression analysis was used to explore the associations between DAL and MetS and its components. Age, energy intake, physical activity, education, marital status, home ownership, socioeconomic status, history of obesity-related disease, and calcium supplements were included in model I. Further adjustment in model II was made for body mass index. Results Higher NEAP scores were associated with increased odds of low high-density lipoprotein cholesterol (HDL-C) in the crude model (OR: 1.26, 95% CI: 1.01-2.56, p trend = 0.06) in women, which was confirmed in the adjusted models. In model I, women in the last quintile of NEAP had 54% greater odds of having hypertriglyceridemia compared to the first quintile (OR: 1.54, 95% CI: 1.007-2.36, p trend = 0.02). This association was still significant and even stronger after further adjustment for BMI (OR: 1.55, 95% CI: 1.01-2.40, p trend = 0.01). In addition, in model I, men in the fourth quintile of NEAP had 5.68-fold greater odds of hyperglycemia compared to the first quintile (OR: 5.68, 95% CI: 1.18-27.25, p trend = 0.11). Similar results were found in the fully adjusted model (OR: 5.89, 95% CI: 1.19-28.99, p trend = 0.54). Conclusion There was no significant association between DAL and MetS. DAL was positively associated with the odds of low HDL-C and hypertriglyceridemia in women. Moreover, moderate DAL (NEAP) was associated with an increased odds of hyperglycemia in men.

Neuro-mucormycosis: Lessons from COVID-19-associated cases.

Background: Scarce data are available on the neurological presentations of coronavirus disease 2019 (COVID-19)-associated mucormycosis (CAM) and COVID-19-unrelated rhino-orbito-cerebral mucormycosis (ROCM). This study aimed to compare the neurological presentations and their associated outcomes in patients with CAM and COVID-19-unrelated ROCM. Methods: In December 2021, a case-control analysis was conducted on the CAM (case group) and COVID-19-unrelated ROCM (control group) referrals of one center in Isfahan, Iran. Confirmed CAM patients from January 2020 to December 2021 constituted the case group, and patients with COVID-19-unrelated ROCM from 2016-2019 constituted the control group. Their data were then analyzed using proper (non) parametric tests and generalized linear models (GLM), therein P-value below 0.05 was considered as the criterion of statistical significance, and the SPSS software was used. Results: After retrieving data on 177 patients with mucormycosis, 78 patients with CAM were included as the case group and 72 patients with COVID-19-unrelated ROCM were included as the control group. Neurological presentations suggestive of second, third, and eighth cranial nerve involvement were more prevalent in the CAM group (all with P < 0.05). The mortality rate in the CAM group was 1.9 times that of the controls (P = 0.01), being explained by higher extent of corticosteroid administration among them. Higher age and presentation with gait ataxia, ptosis, and mydriasis were considered to be predictive of poor prognosis in patients with CAM (all with P < 0.05). Conclusion: The neurological manifestations of CAM differ from COVID-19-unrelated ROCM based on the presented results, some of which are associated with poor prognosis. Further replication is warranted to confirm our retrospective analyses.

Erysipelothrix rhusiopathiae-specific T-cell responses after experimental infection of chickens selectively bred for high and low serum levels of mannose-binding lectin.

Erysipelas, caused by infection with Erysipelothrix rhusiopathiae (ER) is an important emerging disease in laying hens. We have earlier observed prominent mannose-binding lectin (MBL) acute phase responses in experimentally ER infected chickens. The present study aimed to further examine immune responses to ER by using chickens selectively bred for high (L10H) and low (L10L) serum MBL levels. Chickens were infected with ER at 3 weeks of age and immune parameters and bacterial load were monitored in blood until day 18 after infection. Blood and spleen leukocytes collected on day 18 were stimulated in vitro with ER antigens and blast transformation of different T-cell populations was assessed. The ER infection gave a very varied outcome and no clear differences were observed between L10H and L10L chickens with respect to leukocyte counts, bacterial load or clinical outcome. Nonetheless, rapid innate responses, e.g., heterophilia and increased serum MBL levels were noted in bacteraemic chickens. All ER infected chickens also showed transient increased expression of mannose receptor MRC1L-B and decreased expression of major histocompatibility complex II on monocytes day 1 after infection indicating monocyte activation or relocation. In vitro ER stimulation showed antigen specific blast transformation of CD4+, TCRγ/δ-CD8αß+ and TCRγ/δ+CD8αß+ spleen cells from all infected chickens. For CD4+ and TCRγ/δ-CD8αß+ cells the proportions of blast transformed cells were significantly higher for samples from L10L chickens than those for samples from L10H chickens. This is the first observation of ER-specific T-cells in chickens and interestingly a Th1-type response comprising cytotoxic T-cells was indicated.