Takotsubo Cardiomyopathy and Autoimmune Disorders: A Systematic Scoping Review of Published Cases.

Introduction: Takotsubo cardiomyopathy (TCM) features transient left ventricular apical dysfunction or ballooning. The underlying mechanism remains elusive; however, evidence suggests the role of different physical and psychological stressors. We systematically reviewed patients presenting with TCM and autoimmunity to explore the link between the two conditions. Methods: We applied the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) to report this review. Using keywords related to autoimmune/immune-mediated diseases and TCM, we searched PubMed, Scopus, and WOS in March 2022. The final results were added to a data extraction sheet. Data were analyzed by SPSS version 26.0. Results: Our search yielded 121 studies, including 155 patients. Females were considerably predominant. Most patients had a history of autoimmune disease, and almost a third had a history of cardiovascular disease. Dyspnea and chest pain were the most common chief complaints. More than 70% of patients had experienced physical stress. Myasthenia gravis, systemic lupus erythematosus, and multiple sclerosis were the most frequently reported autoimmune diseases. Conclusion: There were similarities in age and sex compared to classic TCM. TCM should be considered as a differential diagnosis for ACS, especially in patients with a positive background of autoimmunity. A precise reporting system is required for further studies.

A Possible Case of Hypertensive Crisis With Aortic Dissection After an Anti-COVID-19 Vaccine.

Aortic dissection, a potentially fatal event, usually presents with acute intense chest or back pain. Painless aortic dissections constitute about 10% of all cases. High blood pressure is a common finding in both painless and painful aortic dissections. During the coronavirus disease (COVID-19) pandemic, various anti-COVID vaccines have been massively used. Although these vaccines are generally safe, there is a small risk of adverse effects which are mostly mild and transient, but sometimes they could be life-threatening. We report a case of painless aortic dissection that occurred within minutes of receiving the COVID-19 inactivated vaccine. A 65-year-old woman with chronic controlled systemic hypertension developed slurred speech, decreased level of consciousness, generalized weakness, and dyspnea without chest, back, or abdominal pain a few minutes after receiving the second dose of inactivated COVID-19 vaccine; she had a systolic blood pressure of 220 mmHg and left-sided pleural effusion. Drainage of the pleural effusion revealed gross blood and a spiral chest and mediastinum CT with intravenous contrast showed a penetrating atherosclerotic ulcer in the descending aorta. Therefore, thoracic endovascular aortic repair (TEVAR) was carried out, and the patient was discharged in satisfactory condition after 3 days.

Antioxidant and anti-apoptotic effects of selenium nanoparticles and Lactobacillus casei on mice testis after X-ray.

Radiation can lead to various damages in the process of spermatogenesis that lead to a decrease in the number of sperm, an increase in spermatogenesis disorders, and defective sperm function. Radioprotectors are considered a good approach to reducing the damage caused by radiation. The goal of this work was to study how X-ray radiation affects testicular tissue and the process of spermatogenesis, as well as the radioprotective effects of selenium nanoparticles (SeNPs) and Lactobacillus casei (L. casei) as probiotic compounds, given alone or together. This study included 64 adult Syrian male mice weighing approximately 20 ± 5 g and aged 10 ± 1 weeks. Animals were randomly divided into eight groups: control group, SeNPs, probiotic, SeNPs and probiotic, X-ray radiation, SeNPs (X-ray), probiotic (X-ray), and SeNPs and probiotic (X-ray). Histology parameters and levels of oxidative stress biomarkers such as catalase, malondialdehyde, superoxide dismutase, and glutathione peroxidase were examined. In addition, the level of apoptosis was measured in testicular cells that had been treated with SeNPs and L. casei as a probiotic. The results showed that the administration of SeNPs or probiotic diminished the effects of X-ray radiation. These compounds induced a significant decreased in malondialdehyde, caspase 3, and caspase 9 gene levels and a remarkable increased in catalase, superoxide dismutase, and Catsper gene expression. SeNPs and probiotic exhibited a potent antioxidant effect and elevated the mean number of spermatogonia cells, sperm cell count, spermatogenesis percentage, and sperm motility percentage. The prescribed compound exhibited an ideal radioprotective effect with the ability to reduce the side effects of ionizing radiation and to protect normal tissues. SeNPs and probiotic inhibit testicular injury and improve the antioxidant state in male mice.

Antiproliferative effects of AAV-delivered CRISPR/Cas9-based degradation of the HPV18-E6 gene in HeLa cells.

Human papillomavirus infections are associated with most cervical cancers, which are the fourth most common cancer in women. HPV-E6 protein binds to protein p53 and inhibits its function, leading to the switching of normal cells toward cancer cells. Here, we disrupted the HPV-E6 gene and investigated its effects on the proliferation and apoptosis of HeLa cells. The HPV18-E6 gene was targeted with two designed sgRNAs cloned into an AAV-CRISPR-based plasmid. The AAV-E6-CRISPR/Cas9 virions were prepared and titrated in HEK293t cells. The cleavage created in the HPV-E6 gene was detected using the T7E1 assay. Cell cycle profiling, MTT assay, and annexin V/PI staining were performed. Also, the p53 protein level was measured by Western blotting. Our data showed that disruption of the HPV-E6 gene led to increased cell apoptosis and decreased cell proliferation. A significant accumulation of infected cells in sub-G1 phase was observed in the cell profiling assay. Also, HPV-E6 gene disruption resulted in a significant increase in the level of P53 protein. Our findings indicated that AAV-mediated delivery of CRISPR/Cas9 can effectively target the HPV-E6 gene in HeLa cells, and its antiproliferative effects may provide therapeutic benefits of local administration of this gene-editing system for HPV-related cervical cancers.

The Protective Effect of Sulforaphane against Oxidative Stress through Activation of NRF2/ARE Pathway in Human Granulosa Cells.

OBJECTIVE: Sulforaphane (SFN) is a natural free radical scavenger that can reduce oxidative stress (OS) through mediating nuclear factor (erythroid-derived 2)-like 2 (NF-E2-related factor 2 or NRF2)/antioxidant response element (ARE) signaling pathway and the downstream antioxidant enzymes. Here, we intended to study the role of SFN in OSinduced human granulosa cells (GCs) by investigating the intracellular levels of reactive oxygen species (ROS), cell death, and NRF2-ARE pathway. MATERIALS AND METHODS: This experimental study was conducted on GCs of 12 healthy women who had normal menstrual cycles with no history of polycystic ovary syndrome (PCOS), endometriosis, menstrual disorders, hyperprolactinemia, or hormonal therapy. After isolation of GCs, the MTT assay was performed to explore GCs viability after treatment with SFN in the presence or absence of H2O2. Flow cytometry was utilized to determine the intracellular ROS production and the apoptosis rate. Evaluation of the mRNA and protein expression levels of NRF2 and phase II enzymes including superoxide dismutase (SOD) and catalase (CAT) was performed by quantitative real-time polymerase chain reaction (PCR) and western blotting. Finally, the data were analyzed by SPSS software using One-way ANOVA and the suitable post-hoc test. Significance level was considered as P<0.05. RESULTS: Pretreatment of GCs with SFN attenuated intracellular ROS production and apoptosis rate in the H2O2-exposed cells. Moreover, SFN treatment increased the mRNA expression level of NRF2, SOD, and CAT. Higher expression of NRF2 and SOD was also observed at the protein level. CONCLUSION: Our study demonstrated that SFN protects human GCs against H2O2 induced-OS by reducing the intracellular ROS production and the following apoptosis through a mechanism by which NRF2 increases the antioxidant enzymes such as SOD and CAT. This result may have a potential application in assisted reproduction cycles by improving the quality of GCs and the embedded oocyte, especially in PCOS patients.

Circular RNA-associated ceRNA network involved in HIF-1 signalling in triple-negative breast cancer: circ_0047303 as a potential key regulator.

The aggressive and highly metastatic nature of triple-negative breast cancer (TNBC) causes patients to suffer from the poor outcome. HIF-1 signalling pathway is a prominent pathway that contributes to angiogenesis and metastasis progression in tumours. On the contrary, the undeniable importance of circular RNAs (circRNAs) as multifunctional non-coding RNAs (ncRNAs) has been identified in breast cancer. These ncRNAs owing to their high stability and specificity have been becoming a hotspot in cancer researches. circRNAs act as competing endogenous RNAs (ceRNAs) and compete with mRNAs for shared miRNAs, thus modulate gene expression. Since the most dysregulated biological functions in TNBC are associated with cellular invasion, understanding the molecular pathogenesis of these processes is a crucial step towards the development of new treatment approaches. The purpose of this study is to undermine the circRNA-associated ceRNA network involved in HIF-1 signalling in TNBC using an integrative bioinformatics approach. In the next step, the novel circ_0047303-mediated ceRNA regulatory axes have been extracted and validated across TNBC samples. We show that circ_0047303 has the highest degree in the circRNA-associated ceRNA network and shows a significant up-expression in TNBC. Moreover, our results suggest that circ_0047303 could mediate the upregulation of key angiogenesis-related genes, including HIF-1, EIF4E2 and VEGFA in TNBC through sponging the tumour-suppressive miRNAs. The circ_0047303 could be a promising molecular biomarker and/or therapeutic target for TNBC.

Anti-IgE monoclonal antibodies as potential treatment in COVID-19.

Coronavirus disease 2019 (COVID-19) is associated with irreversible effects on vital organs, especially the respiratory and cardiac systems. While the immune system plays a key role in the survival of patients to viral infections, in COVID-19, there is a hyperinflammatory immune response evoked by all the immune cells, such as neutrophils, monocytes, and includes release of various cytokines, resulting in an exaggerated immune response, named cytokine storm. This severe, dysregulated immune response causes multi-organ damage, which eventually leads to high mortality. One of the most important components of hypersensitivity is immunoglobulin E (IgE), which plays a major role in susceptibility to respiratory infections and can lead to the activation of mast cells. There is also a negative association between IgE and IFN-α, which can reduce Toll-like receptor (TLR) nine receptor expression and TLR-7 signaling to disrupt IFN production. Moreover, anti-IgE drugs such as omalizumab reduces the severity and duration of COVID-19. In addition to its anti-IgE effect, omalizumab inhibits inflammatory cells such as neutrophils. Hence, blockade of IgE may have clinical utility as an immunotherapy for COVID-19.

Anti-angiogenic effects of testis-specific gene antigen 10 on primary endothelial cells.

Growing evidence indicates the antitumor and antiangiogenesis activities of testis-specific gene antigen 10 (TSGA10). However, the underlying mechanisms and precise role of TSGA10 in angiogenesis are still elusive. In this study, we isolated human umbilical cord vein endothelial cells (HUVECs) and stably transfected with pcDNA3.1 carrying TSGA10 coding sequence. We demonstrated that TSGA10 over-expression significantly decreases HUVEC tubulogenesis and interconnected capillary network formation. HUVECs over-expressing TSGA10 exhibited a significant decrease in migration and proliferation rates. TSGA10 over-expression markedly decreased expression of angiogenesis-related genes, including VEGF-A, VEGFR-2, Ang-1, Ang-2, and Tie-2. Our ELISA results showed the decrease in VEGF-A mRNA expression level is associated with a significant decrease in its protein secretion. Additionally, over-expressing TSGA10 decreased expression levels of marker genes of cell migration (MMP-2, MMP-9, and SDF-1a) and proliferation (PCNA and Ki-67. Furthermore, ERK-1 and AKT phosphorylation significantly reduced in HUVECs over-expressing TSGA10. Our findings suggest a potent anti-angiogenesis activity of TSGA10 in HUVECs through down-regulation of ERK and AKT signalling pathways, and may provide therapeutic benefits for the management of different pathological angiogenesis.

Genotype-phenotype correlation and description of two novel mutations in Iranian patients with glycogen storage disease 1b (GSD1b).

BACKGROUND: Glycogen storage disease (GSD) is a rare inborn error of the synthesis or degradation of glycogen metabolism. GSD1, the most common type of GSD, is categorized into GSD1a and GSD1b which caused by the deficiency of glucose-6-phosphatase (G6PC) and glucose-6-phosphate transporter (SLC37A4), respectively. The high rates of consanguineous marriages in Iran provide a desirable context to facilitate finding the homozygous pathogenic mutations. This study designates to evaluate the clinical and genetic characteristics of patients with GSD1b to assess the possible genotype-phenotype correlation. RESULTS: Autozygosity mapping was performed on nineteen GSD suspected families to suggest the causative loci. The mapping was done using two panels of short tandem repeat (STR) markers linked to the corresponding genes. The patients with autozygous haplotype block for the markers flanking the genes were selected for direct sequencing. Six patients showed autozygosity in the candidate markers for SLC37A4. Three causative variants were detected. The recurrent mutation of c.1042_1043delCT (p.Leu348Valfs*53) and a novel missense mutation of c.365G > A (p.G122E) in the homozygous state were identified in the SLC37A4. In silico analysis was performed to predict the pathogenicity of the variants. A novel whole SLC37A4 gene deletion using long-range PCR and sequencing was confirmed as well. Severe and moderate neutropenia was observed in patients with frameshift and missense variants, respectively. The sibling with the whole gene deletion has shown both severe neutropenia and leukopenia. CONCLUSIONS: The results showed that the hematological findings may have an appropriate correlation with the genotype findings. However, for a definite genotype-phenotype correlation, specifically for the clinical and biochemical phenotype, further studies with larger sample sizes are needed.

Investigation of iron oxide nanoparticle cytotoxicity in relation to kidney cells: A mathematical modeling of data mining.

Iron oxide nanoparticles (IONs) have several applications in medical fields including magnetic resonance imaging (MRI), drug delivery, cancer treatment and cell splitting. Therefore, it is important to investigate their cellular toxicity. It is difficult to predict their cellular toxicity due to complexities associated with their cellular mechanisms. The present study was designed to collect data on the cell viability of IONs and obtain a mathematical modeling. For this purpose, particle size, concentration, incubation time and the surface charge of NPs were selected as the model inputs and the percentage of cell viability (%CV) as the model output. Using a version of the modeling called SA-LOOCV-GRBF, these issues can be resolved with favorable results. Since the behavior of positive zeta potential (PZP) is different from negative zeta potential (NZP), they were compared by separate modeling efforts. Kidney is a vital body organ that dispose of IONs in the body, but it is possible that these cells engage in unwanted interactions with IONs. Therefore, the kidney cell line was examined in this study.

Long non-coding RNAs: Diverse roles in various disorders.

BACKGROUND: Long non-coding RNAs (lncRNAs) are a group of transcripts larger than 200 nucleotides that are not translated to proteins. These transcripts regulate expression of numerous genes at different levels by acting as decoys, scaffolds, and enhancers. Thus they regulate cell development, differentiation and fate. OBJECTIVE: To find the role of lncRNAs in various diseases. METHODS: We searched PubMed and google scholar and summarized the data regarding the role of lncRNAs in cancer and neurologic disorders. RESULTS: Several recent studies have shown that their expressions are up-/down-regulated in malignant tissues. Consequently, they have suggested that lncRNAs can differentiate cancer samples from normal samples. Their application as biomarker is not limited to cancers. In several neurologic or psychiatric disorders researchers have found aberrant expression of lncRNAs. CONCLUSIONS: Taken together, lncRNAs constitute a novel vast area of research to find answer to fundamental biologic questions.

Improving Depression, and Quality of Life in Patients with Type 2 Diabetes: Using Group Cognitive Behavior Therapy.

Objective: Depression is a chronic condition comorbid with diabetes type 2 that often remains untreated. Dealing with diabetes is a challenging task for patients and can lead to depression in long term. These two conditions have a negative influence on each other and on the individual's quality of life. The purpose of this study was to investigate the effect of group cognitive behavior therapy on depression, quality of life in women with diabetes type 2. Method: We conducted a clinical trial among 30 women with diabetes type 2 comorbid with depression. The women were divided randomly into the two groups of intervention and control. Each group consisted of 15 individuals. The intervention group received 10 sessions of group cognitive behavior therapy while the control group didn't. Results: The results suggested that group cognitive-behavior therapy decreased depression symptoms (F=72.17, p<0.001), and improved quality of life of the patients (F=8.82, p<0.05) of the intervention group compared to the control group. Conclusion: The results shows that group cognitive behavior therapy can affect depression symptoms, and consequently patients' quality of life with diabetes type 2.

Assessment of dental student satisfaction with regard to process of thesis educational courses.

INTRODUCTION: Ensuring achievement of research experience by students is one of the most important goals of the thesis-conduction process and evaluation of student satisfaction with this process is one of the most imperative challenges herein. AIMS: The aim of this study is to investigate the satisfaction of dental students passing the thesis educational course from the Isfahan Dental School. SETTINGS AND DESIGN: Sixty-two dental students who had graduated in2011, from the Isfahan Dental School, participated in this descriptive cross-sectional study. MATERIALS AND METHODS: The postgraduate Research Experience Questionnaire (PREQ) was used for data collection. The questionnaire evaluated student satisfaction in seven domains: Thesis supervision, skill development, intellectual climate, infrastructure, thesis examination, goals and expectations, and overall satisfaction. STATISTICAL ANALYSIS USED: The data were analyzed on an SPSS software using descriptive and inferential statistics. RESULTS: The mean score of satisfaction of the participants was 75 ± 12. On the basis of their scores, satisfaction in 3.2% of them was slow, in 33.9%was medium, in 61.3% was good and in 1.6% was high. The highest satisfaction was found to be in thesis supervision and the least was in the intellectual climate domain. There was no significant statistical difference between satisfaction and gender (P = 0.46). CONCLUSIONS: Considering the results, to increase student satisfaction for passing the thesis courses, it is necessary to improve the intellectual climate in dental schools and also increase the research budget for more financial support of students to carry out their projects.

Present technology and future trends in point-of-care microfluidic diagnostics.

This work reviews present technologies and developing trends in Point-of-Care (POC) microfluidic diagnostics platforms. First, various fluidics technologies such as pressure-driven flows, capillary flows, electromagnetically driven flows, centrifugal fluidics, acoustically driven flows, and droplet fluidics are categorized. Then three broad categories of POC microfluidic testing devices are considered: lateral flow devices, desktop and handheld POC diagnostic platforms, and emergent molecular diagnostic POC systems. Such evolving trends as miniaturization, multiplexing, networking, new more sensitive detection schemes, and the importance of sample processing are discussed. It is concluded that POC microfluidic diagnostics has a potential to improve patient treatment outcome and bring substantial savings in overall healthcare costs.

The effect of vitamin D supplementation on bone formation around titanium implants in diabetic rats.

BACKGROUND: Diabetes has become the next most widespread disease after cancer. Recent studies have found that diabetes and moderate to severe vitamin D deficiency are associated with reduced bone mineral content; therefore administration of vitamin D may correct these conditions. The purpose of this research is to compare the effect of vitamin D administration on bone to implant contact in diabetic rats with control group. MATERIALS AND METHODS: In this randomized placebo-controlled trial, 48 Wistar rats were rendered diabetic (130≤ blood sugar ≤200 mg/dl) by IV injection of 35 mg/kg Alloxan. Implants were inserted in tibial bone; Then rats were divided into study and control groups and received oral vitamin D3 (160 IU) or placebo respectively for one week. Bone to implant contact value was measured under light microscope at 3 and 6 weeks. RESULTS: Analysis of data indicated that vitamin D had no significant effect on bone to implant contact (BIC). At 3 weeks, the control group (n = 5) reported BIC level at 44 ± 19 and study group (n = 7) at 57 ± 20. At 6 weeks, the control group (n = 5) reported BIC level at 70 ± 29, and study group (n = 10) at 65 ± 22. Twenty one samples were missed because of death or incorrect lab processes. CONCLUSION: It seems that vitamin D supplement has no significant effect on BIC in 130 mg/dL ≤ blood sugar ≤200 mg/dL (P = 0.703) andwas also not time dependent (P = 0.074).

A multiplexed immunoassay system based upon reciprocating centrifugal microfluidics.

A novel, centrifugal disk-based micro-total analysis system (µTAS) for low cost and high throughput semi-automated immunoassay processing was developed. A key innovation in the disposable immunoassay disk design is in a fluidic structure that enables very efficient micro-mixing based on a reciprocating mechanism in which centrifugal acceleration acting upon a liquid element first generates and stores pneumatic energy that is then released by a reduction of the centrifugal acceleration, resulting in a reversal of direction of flow of the liquid. Through an alternating sequence of high and low centrifugal acceleration, the system reciprocates the flow of liquid within the disk to maximize incubation/hybridization efficiency between antibodies and antigen macromolecules during the incubation/hybridization stage of the assay. The described reciprocating mechanism results in a reduction in processing time and reagent consumption by one order of magnitude.

Reciprocating flow-based centrifugal microfluidics mixer.

Proper mixing of reagents is of paramount importance for an efficient chemical reaction. While on a large scale there are many good solutions for quantitative mixing of reagents, as of today, efficient and inexpensive fluid mixing in the nanoliter and microliter volume range is still a challenge. Complete, i.e., quantitative mixing is of special importance in any small-scale analytical application because the scarcity of analytes and the low volume of the reagents demand efficient utilization of all available reaction components. In this paper we demonstrate the design and fabrication of a novel centrifugal force-based unit for fast mixing of fluids in the nanoliter to microliter volume range. The device consists of a number of chambers (including two loading chambers, one pressure chamber, and one mixing chamber) that are connected through a network of microchannels, and is made by bonding a slab of polydimethylsiloxane (PDMS) to a glass slide. The PDMS slab was cast using a SU-8 master mold fabricated by a two-level photolithography process. This microfluidic mixer exploits centrifugal force and pneumatic pressure to reciprocate the flow of fluid samples in order to minimize the amount of sample and the time of mixing. The process of mixing was monitored by utilizing the planar laser induced fluorescence (PLIF) technique. A time series of high resolution images of the mixing chamber were analyzed for the spatial distribution of light intensities as the two fluids (suspension of red fluorescent particles and water) mixed. Histograms of the fluorescent emissions within the mixing chamber during different stages of the mixing process were created to quantify the level of mixing of the mixing fluids. The results suggest that quantitative mixing was achieved in less than 3 min. This device can be employed as a stand alone mixing unit or may be integrated into a disk-based microfluidic system where, in addition to mixing, several other sample preparation steps may be included.