Physical Activity Promotion in Schools Using Theoretically Designed Mobile Phone Application.

Background: Regular physical activity for adolescents has many health benefits, many of which also affect adulthood. Physical activity is a behavior that requires planning and choosing an appropriate educational method, model, or theory. However, mobile phone applications are known as a suitable method to increase physical activity according to the guidelines. This study aims to increase physical activity in female students based on the theory of planned behavior using mobile phone applications. Methods: This quasi-experimental study was implemented on 220 high school students (110 people in each group). The samples were selected by a multi-stage cluster method and their information was collected by the International Physical Activity Questionnaire (IPAQ) and the Theory of Planned Behavior (TPB) questionnaire whose validity and reliability were confirmed. The intervention group received 8 sessions of education through a mobile phone application that was designed by the constructs of the theory of planned behavior. The samples were evaluated in three stages, through a pre-test, post-test, and two-month follow-up. Results: The results showed a significant difference in the post-test and two months after the intervention between intervention and control groups in terms of attitude, perceived behavioral control, intention, and physical activity. There was a significant difference between intervention and control groups in subjective norms in the post-test, but there was no significant difference in the two-month follow-up compared to the post-test (P = 0.08). Conclusions: An educational intervention based on the theory of planned behavior using mobile phone applications led to an increase in the physical activity of girl high school students. However, to determine the full effectiveness of this study, it is recommended to implement this intervention in all schools.

Bacillus coagulans T4 and Lactobacillus paracasei TD3 Ameliorate Skeletal Muscle Oxidative Stress and Inflammation in High-Fat Diet-Fed C57BL/6J Mice.

Background: This study aims to investigate the effects of Bacillus coagulans T4 and Lactobacillus paracasei TD3 probiotics on skeletal muscle inflammation and oxidative stress in C57BL/6J mice fed a high-fat diet (HFD). Methods: Probiotics B. coagulans T4, and L. paracasei TD3 were administered to male C57BL/6J mice fed with HFD. The gene expression of macrophage infiltration markers, inflammatory cytokines, and oxidative stress indicators in the muscle tissue was investigated. Results: Treatment with B. coagulans T4 and L. paracasei TD3 reduced macrophage infiltration, accompanied by a decrease in the expression of monocyte chemoattractant protein-1 (MCP-1) and an increase in the expression of interleukin (IL)-10. On the other hand, L. paracasei TD3 decreased malondialdehyde (MDA) while B. coagulans T4 decreased carbonyl and increased catalase activity. Conclusions: Treatment with probiotics B. coagulans T4 and L. paracasei TD3 partially ameliorated obesity-induced skeletal muscle inflammation in HFD-fed mice.

Laboratory Scale Production of Complex Proteins Using Charge Complimentary Nanoenvironments.

Protein refolding is a crucial procedure in bacterial recombinant expression. Aggregation and misfolding are the two challenges that can affect the overall yield and specific activity of the folded proteins. We demonstrated the in vitro use of nanoscale "thermostable exoshells" (tES) to encapsulate, fold and release diverse protein substrates. With tES, the soluble yield, functional yield, and specific activity increased from 2-fold to >100-fold when compared to folding in its absence. On average, the soluble yield was determined to be 6.5 mg/100 mg of tES for a set of 12 diverse substrates evaluated. The electrostatic charge complementation between the tES interior and the protein substrate was considered as the primary determinant for functional folding. We thus describe a useful and simple method for in vitro folding that has been evaluated and implemented in our laboratory.

The high-intensity interval training (HIIT) and curcumin supplementation can positively regulate the autophagy pathway in myocardial cells of STZ-induced diabetic rats.

OBJECTIVE: Targeting autophagy is a new therapeutic strategy for the complications of diabetes,such as diabetic cardiomyopathy (DCM). During diabetes, increased or insufficient autophagic activity causes aberrations in cellular homeostasis. Regarding the conflicting and unclear results regarding the effect of HIIT and curcumin supplementation on the expression of genes associated to autophagy, this study aimed to assess whether 4-week high-intensity interval training (HIIT) and curcumin supplementation are able to influence the expression of autophagy-related genes in myocardial cells of diabetic rats. METHODS: In an experimental design, 24 male Wistar rats were randomly divided into 4 groups: non-diabetic control (NC), diabetic control (DC), diabetes + HIIT (D + HIIT), and diabetes + curcumin (D + CU). After HIIT program and curcumin treatment, the genes expression of autophagy pathway were assessed in the myocardium by real-time PCR Tanique. RESULTS: The results indicated that the expression levels of ATG1, Beclin1, ATG5, and LAMP-2 genes were significantly reduced in the DC group compared to the NC group (p < 0.001). Following 4-week HIIT, the expression of Beclin1, ATG-5, and LAMP-2 improved considerably compared to the DC group (p < 0.001, p < 0.001, and p < 0.05, respectively). In addition, after 4 weeks of curcumin supplementation, the expression levels of ATG-5 and Beclin-1 were significantly improved compared to the DC group (p < 0.001, p < 0.05, respectively). It seems HIIT and curcumin supplementation can be an effective approach for inducing autophagy and improving cardiac function in DCM rats.However, HIIT seems more effective than curcumin in this regard.

Evaluation of the effect of fish oil in the prevention of pressure ulcers in patients admitted to the intensive care unit.

Introduction: Today, the anti-inflammatory property of fish oil is used to heal wounds, but this property has not been investigated to prevent the occurrence of pressure ulcers. So the research team decided to evaluate this feature as well. Materials and methods: This clinical trial study was performed on 102 patients admitted to the intensive care unit located at Besat Hospital in 2020. Samples were assigned to three groups control, placebo, and intervention using permutation blocks. Before the intervention, the questionnaire of demographic and clinical variables, level of consciousness, Braden scale, and short nutritional status questionnaire was completed by the main researcher. In the intervention group, in addition to routine care, 2 cc of fish oil was gently rubbed into the sacrum once a day for 5 days. The same intervention was repeated in the placebo group, with the difference that soybean oil was used instead of fish oil, and the control group received only the usual care. The daily evaluation of pressure ulcers by one of the ICU nurses lasted up to 6 days. Results: The results showed that there was a significant difference in the incidence of pressure ulcers in the three groups (P = 0.043). The risk of pressure ulcers in the control group was 11.9 and 2.7 times higher than the fish oil group and placebo group (P = 0.023) & (P = 0.132). Conclusion: The use of topical fish oil can be effective in preventing pressure ulcers.

Design and Fabrication of a DNA-copper Nanocluster-based Biosensor for Multiple Detections of Circulating miRNAs in Early Screening of Breast Cancer.

Breast cancer is one of the most prevalent cancers and a significant cause of fatalities in women. Diagnosis of breast cancer faces substantial challenges, owing to the multi-factored nature of the illness. Thus, the necessity for an inexpensive, rapid, and non-invasive diagnostic method that enables early detection with high sensitivity and specificity is of primary significance. In this study, a biosensor based on the fluorescence emission of DNA-templated Cu nanoclusters was designed to simultaneously detect and quantify three significant biomarkers of breast cancer (circulating microRNAs, miR-21, miR-195, and miR-155). Fluorescence spectroscopy, FESEM and TEM microscopy, and DLS confirmed the validation of the biosensor. A detection limit of 1.7 pM with a linearity range of 500 nM to 3 µM was obtained. In conclusion, the innovative selection of three biomarkers, the utilization of the HCR process, and an the elaborated design of probes are considered to be among the most important advantages of this biosensor, enabling it a simultaneous triple diagnosis of the blood specific circulating microRNAs without a need for any enzymes, thermo-cycles, expensive or complex facilities, linkers, fluorescent tags, and time-consuming methods.

Gastrointestinal Tract Stabilized Protein Delivery Using Disulfide Thermostable Exoshell System.

Thermostable exoshells (tES) are engineered proteinaceous nanoparticles used for the rapid encapsulation of therapeutic proteins/enzymes, whereby the nanoplatform protects the payload from proteases and other denaturants. Given the significance of oral delivery as the preferred model for drug administration, we structurally improved the stability of tES through multiple inter-subunit disulfide linkages that were initially absent in the parent molecule. The disulfide-linked tES, as compared to tES, significantly stabilized the activity of encapsulated horseradish peroxidase (HRP) at acidic pH and against the primary human digestive enzymes, pepsin, and trypsin. Furthermore, the disulfide-linked tES (DS-tES) exhibited significant intestinal permeability as evaluated using Caco2 cells. In vivo bioluminescence assay showed that encapsulated Renilla luciferase (rluc) was ~3 times more stable in mice compared to the free enzyme. DS-tES collected mice feces had ~100 times more active enzyme in comparison to the control (free enzyme) after 24 h of oral administration, demonstrating strong intestinal stability. Taken together, the in vitro and in vivo results demonstrate the potential of DS-tES for intraluminal and systemic oral drug delivery applications.

Bioorthogonal Catalysis for Treatment of Solid Tumors Using Thermostable, Self-Assembling, Single Enzyme Nanoparticles and Natural Product Conversion with Indole-3-acetic Acid.

Bioorthogonal catalysis (BC) generates chemical reactions not present in normal physiology for the purpose of disease treatment. Because BC catalytically produces the desired therapy only at the site of disease, it holds the promise of site-specific treatment with little or no systemic exposure or side effects. Transition metals are typically used as catalytic centers in BC; however, solubility and substrate specificity typically necessitate a coordinating enzyme and/or stabilizing superstructure for in vivo application. We report the use of self-assembling, porous exoshells (tESs) to encapsulate and deliver an iron-containing reaction center for the treatment of breast cancer. The catalytic center is paired with indole-3-acetic acid (IAA), a natural product found in edible plants, which undergoes oxidative decarboxylation, via reduction of iron(III) to iron(II), to produce free radicals and bioactive metabolites. The tES encapsulation is critical for endocytic uptake of BC reaction centers and, when followed by administration of IAA, results in apoptosis of MDA-MB-231 triple negative cancer cells and complete regression of in vivo orthotopic xenograft tumors (p < 0.001, n = 8 per group). When Renilla luciferase (rLuc) is substituted for horseradish peroxidase (HRP), whole animal luminometry can be used to monitor in vivo activity.

Confined-based catalyst investigation through the comparative functionalization and defunctionalization of Zr-MOF.

In metal-organic frameworks, confined space as a chemical nanoreactor is as important as organocatalysis or coordinatively unsaturated metal site catalysis. In the present study, a set of mixed-ligand structures with UiO-66 architecture have been prepared. To the best of our knowledge, for the first time, structures derived by the solvothermal mixing ligand method and ultrasonic-assisted linker exchange approaches have been compared. Additionally, the relationship between the preparation method, structural properties, and catalytic efficiency of the prepared materials in the Knoevenagel condensation of aldehydes has been investigated. The prepared catalyst is very stable and can be recovered and reused for at least ten periods.

Long non-coding RNA MIR4435-2HG: a key molecule in progression of cancer and non-cancerous disorders.

MIR4435-2HG (LINC00978) is a long non-coding RNA (lncRNA) that acts as an oncogene in almost all cancers. This lncRNA participates in the molecular cascades involved in other disorders such as coronary artery diseases, osteonecrosis, osteoarthritis, osteoporosis, and periodontitis. MIR4435-2HG exerts its functions via the spectrum of different mechanisms, including inhibition of apoptosis, sponging microRNAs (miRNAs), promoting cell proliferation, increasing cell invasion and migration, and enhancing epithelial to mesenchymal transition (EMT). MIR4435-2HG can regulate several signaling pathways, including Wnt, TGF-ß/SMAD, Nrf2/HO-1, PI3K/AKT, MAPK/ERK, and FAK/AKT/ß­catenin signaling pathways; therefore, it can lead to tumor progression. In the present review, we aimed to discuss the potential roles of lncRNA MIR4435-2HG in developing cancerous and non-cancerous conditions. Due to its pivotal role in different disorders, this lncRNA can serve as a potential biomarker in future investigations. Moreover, it may serve as a potential therapeutic target for the treatment of various diseases.

Nanostructures in non-invasive prenatal genetic screening.

Prenatal screening is an important issue during pregnancy to ensure fetal and maternal health, as well as preventing the birth of a defective fetus and further problems such as extra costs for the family and society. The methods for the screening have progressed to non-invasive approaches over the recent years. Limitations of common standard screening tests, including invasive sampling, high risk of abortion and a big delay in result preparation have led to the introduction of new rapid and non-invasive approaches for screening. Non-invasive prenatal screening includes a wide range of procedures, including fetal cell-free DNA analysis, proteome, RNAs and other fetal biomarkers in maternal serum. These biomarkers require less invasive sampling than usual methods such as chorionic villus sampling, amniocentesis or cordocentesis. Advanced strategies including the development of nanobiosensors and the use of special nanoparticles have provided optimization and development of NIPS tests, which leads to more accurate, specific and sensitive screening tests, rapid and more reliable results and low cost, as well. This review discusses the specifications and limitations of current non-invasive prenatal screening tests and introduces a novel collection of detection methods reported studies on nanoparticles' aided detection. It can open a new prospect for further studies and effective investigations in prenatal screening field.

Nanoencapsulation as a General Solution for Lyophilization of Labile Substrates.

Protein macromolecules occur naturally at the nanoscale. The use of a dedicated nanoparticle as a lyophilization excipient, however, has not been reported. Because biopolymeric and lipid nanoparticles often denature protein macromolecules and commonly lack the structural rigidity to survive the freeze-drying process, we hypothesized that surrounding an individual protein substrate with a nanoscale, thermostable exoshell (tES) would prevent aggregation and protect the substrate from denaturation during freezing, sublimation, and storage. We systematically investigated the properties of tES, including secondary structure and its homogeneity, throughout the process of lyophilization and found that tES have a near 100% recovery following aqueous reconstitution. We then tested the hypothesis that tES could encapsulate a model substrate, horseradish peroxidase (HRP), using charge complementation and pH-mediated controlled assembly. HRP were encapsulated within the 8 nm internal tES aqueous cavity using a simplified loading procedure. Time-course experiments demonstrated that unprotected HRP loses 95% of activity after 1 month of lyophilized storage. After encapsulation within tES nanoparticles, 70% of HRP activity was recovered, representing a 14-fold improvement and this effect was reproducible across a range of storage temperatures. To our knowledge, these results represent the first reported use of nanoparticle encapsulation to stabilize a functional macromolecule during lyophilization. Thermostable nanoencapsulation may be a useful method for the long-term storage of labile proteins.

A general approach to protein folding using thermostable exoshells.

In vitro protein folding is a complex process which often results in protein aggregation, low yields and low specific activity. Here we report the use of nanoscale exoshells (tES) to provide complementary nanoenvironments for the folding and release of 12 highly diverse protein substrates ranging from small protein toxins to human albumin, a dimeric protein (alkaline phosphatase), a trimeric ion channel (Omp2a) and the tetrameric tumor suppressor, p53. These proteins represent a unique diversity in size, volume, disulfide linkages, isoelectric point and multi versus monomeric nature of their functional units. Protein encapsulation within tES increased crude soluble yield (3-fold to >100-fold), functional yield (2-fold to >100-fold) and specific activity (3-fold to >100-fold) for all the proteins tested. The average soluble yield was 6.5 mg/100 mg of tES with charge complementation between the tES internal cavity and the protein substrate being the primary determinant of functional folding. Our results confirm the importance of nanoscale electrostatic effects and provide a solution for folding proteins in vitro.

Battling Chemoresistance in Cancer: Root Causes and Strategies to Uproot Them.

With nearly 10 million deaths, cancer is the leading cause of mortality worldwide. Along with major key parameters that control cancer treatment management, such as diagnosis, resistance to the classical and new chemotherapeutic reagents continues to be a significant problem. Intrinsic or acquired chemoresistance leads to cancer recurrence in many cases that eventually causes failure in the successful treatment and death of cancer patients. Various determinants, including tumor heterogeneity and tumor microenvironment, could cause chemoresistance through a diverse range of mechanisms. In this review, we summarize the key determinants and the underlying mechanisms by which chemoresistance appears. We then describe which strategies have been implemented and studied to combat such a lethal phenomenon in the management of cancer treatment, with emphasis on the need to improve the early diagnosis of cancer complemented by combination therapy.

Predicting the Shapes of Protein Complexes through Collision Cross Section Measurements and Database Searches.

In structural biology, collision cross sections (CCSs) from ion mobility mass spectrometry (IM-MS) measurements are routinely compared to computationally or experimentally derived protein structures. Here, we investigate whether CCS data can inform about the shape of a protein in the absence of specific reference structures. Analysis of the proteins in the CCS database shows that protein complexes with low apparent densities are structurally more diverse than those with a high apparent density. Although assigning protein shapes purely on CCS data is not possible, we find that we can distinguish oblate- and prolate-shaped protein complexes by using the CCS, molecular weight, and oligomeric states to mine the Protein Data Bank (PDB) for potentially similar protein structures. Furthermore, comparing the CCS of a ferritin cage to the solution structures in the PDB reveals significant deviations caused by structural collapse in the gas phase. We then apply the strategy to an integral membrane protein by comparing the shapes of a prokaryotic and a eukaryotic sodium/proton antiporter homologue. We conclude that mining the PDB with IM-MS data is a time-effective way to derive low-resolution structural models.

ErbB4 3'-UTR Variant (c.*3622A>G) is Associated with ER/PR Negativity and Advanced Breast Cancer.

A genetic variant may alter a gene expression level and as a result be associated with pathological characteristics in breast cancer. In this research, the frequency and association of the ErbB4 3'-untranslated region (3'-UTR) variant, rs12471583 (c.*3622A>G) was studied in an Iranian breast cancer patients. In silico assessment was performed to predict the function of the rs12471583 variant located on the 3'-UTR of ErbB4. Furthermore, as a case-control study, this polymorphism was genotyped in 243 breast cancer patients and non-cancerous controls using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. The Armitage's trend test and regular association tests were performed to analyze a possible association between the rs12471583 and risk of breast cancer and its relevant pathological traits. The bioinformatics analysis predicted that the rs12471583 SNP is located on the four miRNA binding sites, including miR-511-5p, miR-4659a-5p, miR-4659b-5p, and miR-6830-3p. According to logistic regression tests, the G allele is negatively associated with ER- (OR = 0.20, 95% C.I. = 0.04-0.93, p = 0.026), PR- (OR = 0.31, 95% C.I. = 0.10-0.98, p = 0.039), ER-/PR- (OR = 0.20, 95% C.I. = 0.04-0.93, p = 0.026), and advanced breast cancer (OR = 0.40, 95% C.I. = 0.18-0.85, p = 0.016). It has been found that ErbB4 expression may be linked to unfavorable outcomes in breast cancer. Likewise, our results suggest that the G allele may strengthen miRNA-ErbB4 binding efficiency and as a result reduce expression of ErbB4. This is a possible explanation for the observed association.

Oral administration of protein nanoparticles: An emerging route to disease treatment.

Over the last two decades, developments in nanomedicine have resulted in technical advances with application to clinical science. Both organic and inorganic nanoparticles (NPs) have shown tolerability, pharmacologic specificity and biodegradability. A subclass of NPs, protein NPs, have garnered recent attention due to the inherent biocompatibility of protein substrates. Protein NPs are currently being employed widely in pharmaceuticals development with applications in nasal, pulmonary, intravenous, ocular and oral delivery. Despite the distinct advantages of orally administered pharmaceuticals, the development of oral delivery systems has been comparatively limited. Therefore, this review attempts to discuss the most recent experimental and pre-clinical findings in the development of protein NPs for oral delivery, while envisioning upcoming challenges.

Subtypes of Antiphospholipid Antibodies in Neurologic Disorders: An Observational Study.

BACKGROUND AND OBJECTIVES: Concomitant neurologic manifestations and positive antiphospholipid antibodies (APAs) have been investigated in different manners. The present study aimed to investigate the association between neurologic manifestations and APAs. MATERIALS AND METHODS: This cross-sectional descriptive study was conducted on 100 consecutive patients with selected neurological manifestations and at least one positive APAs within the age range of 20-50 years, referred to the Rheumatic Diseases Research Center from the Northeast Central Neurology Department of Iran during August 2012 to March 2014. RESULTS: According to the results, 89% of the participants were persistently positive for APAs, including lupus anticoagulant, IgG anticardiolipin (aCL), IgM aCL, IgG ß-2 glycoprotein 1 (ß2- GP1), and IgM ß2-GP1, observed in 16%, 41%, 42%, 17%, and 15% of the patients, respectively. Furthermore, 10% of the patients had concomitant lupus manifestations, and 37% of them showed anti-DNA. The IgG and IgM aCL were the most prevalent antibodies. Cerebral vascular accident (33%), retinal artery/vein occlusion (21%), and seizure (20%) were the most frequent presentations among the patients. In addition, the patients with multiple sclerosis (composing 3% of the subjects) were 100% positive for IgG and IgM aCL, as well as lupus anticoagulant. In addition, IgM anti-ß2- GP1 was 100% positive in optic neuritis patients (composing 5% of the subjects) and was significantly associated with this neurologic disorder. IgM anti-ß2-GP1 was also prevalent in the cases with Guillain-Barré syndrome. The most prevalent persistently positive antibody in the patients with cerebrovascular accident was IgM aCL. CONCLUSION: The findings of this study revealed some associations between the subtypes of APAs and incidence of neurologic disorders. However, the exact correlation between those symptoms and APAs needs further investigations.

The association between rs1972820 and the risk of breast cancer in Isfahan population.

CONTEXT: A number of single nucleotide polymorphisms (SNPs) in ERBB4 gene have been linked to increase the risk of breast cancer. However, no study has been dedicated to analyze the significance of microRNA-related SNP rs1972820, located in ERBB4 3'-untranslated region (UTR), in breast tumors. AIMS: Here, we investigated the frequency and association between rs1972820 and breast cancer. SUBJECTS AND METHODS: The rs1972820 genotypes in 182 samples were collected from 96 healthy people, and 86 breast cancer patients were determined using tetra-primer amplification refractory mutation system-polymerase chain reaction. The frequency of genotypes was analyzed to find the association between rs1972820 and breast cancer risk. STATISTICAL ANALYSIS USED: Conditional logistic regression, odds ratios (ORs), the associated 95% confidence intervals (CIs), and Armitage's test were used in this study. RESULTS: In silico analysis suggested that rs1972820 located in the 3'UTR of ERBB4 gene affects the binding affinity of miR-3144-3p a potential oncomiRNA. Statistical analysis showed a significant association between SNP rs1972820 G allele and reduced breast cancer risk, odds ratio = 0.443 (95% CI: 0.196-0.998). CONCLUSIONS: rs1972820 SNP allele is significantly associated with the reduced risk of breast cancer and could be considered as a potential marker for breast cancer predisposition in population of Isfahan.

Cooverexpression of EpCAM and c-myc genes in malignant breast tumours.

The overexpression of epithelial cell adhesion molecule (EpCAM), a proto-oncogene, affects progression, treatment, and diagnosis of many adenocarcinomas. C-myc has been shown to be a downstream target of EpCAM and is also one of the most important proto-oncogenes routinely overexpressed in breast cancer. However, cooverexpression of EpCAM and c-myc genes has not been investigated in breast cancer tissues, particularly in Iranian population. The aim of this study was to assess the expression of EpCAM and c-myc genes in malignant breast cancer tissues using reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR) followed by analyses of the association between the outcomes. In this study, 122 fresh tissues, including 104 malignant and 18 benign samples, were disrupted by mortar and pestle, and then the RNA was isolated from the samples and converted to cDNA. The relative expression levels of EpCAM and c-myc genes were measured by 2-ΔΔCt method using RT-qPCR. EpCAM protein level was also assessed in 66 cases using Western blot technique. Using RT-qPCR method, our results showed that EpCAM was overexpressed in 48% of malignant and 11.1% of benign samples. Evaluating EpCAM protein overexpression in a portion of samples depicted the fully concordance rate between Western blot and RT-qPCR techniques. C-myc expression was first evaluated by RT-qPCR method, showing the overexpression rate of 39% and 28% in malignant and benign samples, respectively. These data were also quite concordant with the clinically available immunohistochemistry reports of the same samples studied in this study. Importantly, overexpression of EpCAM and c-myc was significantly associated and showed an agreement of 57.3%. This study demonstrated the cooverexpression of EpCAM and c-myc in breast tumours collected from breast cancer patients of the Iranian population. EpCAM and c-myc positive cases were significantly associated with reduced and enhanced risk of ER/PR positivity respectively. However, both were associated with grade III of breast cancer.