Alteration in DNA methylation patterns: Epigenetic signatures in gastrointestinal cancers.

Abnormalities in epigenetic modifications can cause malignant transformations in cells, leading to cancers of the gastrointestinal (GI) tract, which accounts for 20% of all cancers worldwide. Among the epigenetic alterations, DNA hypomethylation is associated with genomic instability. In addition, CpG methylation and promoter hypermethylation have been recognized as biomarkers for different malignancies. In GI cancers, epigenetic alterations affect genes responsible for cell cycle control, DNA repair, apoptosis, and tumorigenic-specific signaling pathways. Understanding the pattern of alterations in DNA methylation in GI cancers could help scientists discover new molecular-based pharmaceutical treatments. This study highlights alterations in DNA methylation in GI cancers. Understanding epigenetic differences among GI cancers may improve targeted therapies and lead to the discovery of new diagnostic biomarkers.

Educational intervention of parents and teachers for children with attention deficit hyperactivity disorder.

BACKGROUND: Educating parents and teachers is very important in managing child behavior, so the present study investigates the effect of parent-teacher educational intervention on reducing ADHD symptoms in children. MATERIALS AND METHOD: This quasi-experimental study with a randomized control group before and after. The multi-stage cluster sampling method was used in this study. Seventy-two children and their parents and teachers participated in this study. They were selected using the multistage cluster sampling method and randomly divided into two groups of test and control. Data collected by CSI-4 questionnaire and researcher-made questionnaires (knowledge, attitude, practice) of parents and teachers. Parents and teacher in test group participated in training sessions. Student's ADHD symptoms were assessed before and after the educational intervention. RESULTS: In this study, the mean (SD) age of the parents was 37.28 (6.24) and the age of the teacher was 45.50 (6/45). Covariance test show that, two months after the intervention, based on parent and teacher report, the mean total score of attention was increase significantly only in test group students. Also, the mean total of hyperactivity score was decreased significantly only in test group students (P < 0.001). Also, the score of knowledge, attitude, and practice of parents as well as teachers 2 months after the intervention was significantly higher than the control group (P < 0.001). CONCLUSION: Parents and teachers training and developing appropriate strategies to increase their awareness, attitude, and practice can diminish ADHD symptoms in all three aspects including inattention and reduce the side effects of ADHD. Planning in educating parents and teacher is essential to prevent impulsive and hyperactive behaviors.

Review on Kidney-Liver Crosstalk: Pathophysiology of Their Disorders.

Kidney-liver crosstalk plays a crucial role in normal and certain pathological conditions. In pathologic states, both renal-induced liver damage and liver-induced kidney diseases may happen through these kidney-liver interactions. This bidirectional crosstalk takes place through the systemic conditions that mutually influence both the liver and kidneys. Ischemia and reperfusion, cytokine release and pro-inflammatory signaling pathways, metabolic acidosis, oxidative stress, and altered enzyme activity and metabolic pathways establish the base of this interaction between the kidneys and liver. In these concomitant kidney-liver diseases, the survival rates strongly correlate with early intervention and treatment of organ dysfunction. Proper care of a nephrologist and hepatologist and the identification of pathological conditions using biomarkers at early stages are necessary to prevent the complications induced by this complex and potentially vicious cycle. Therefore, understanding the characteristics of this crosstalk is essential for better management. In this review, we discussed the available literature concerning the detrimental effects of kidney failure on liver functions and liver-induced kidney diseases.

Association of polymorphism of IL-17A, IL-17F, and IL-6 with Toxoplasma gondii infection susceptibility in HIV/AIDS patients in Shiraz, southern Iran.

INTRODUCTION: Toxoplasma gondii infection is considered as one of the most important opportunistic infections and cause of death in HIV patients. METHODS: In this cross-sectional study, 334 HIV positive patients were included. The molecular test was performed by the restriction fragment length polymorphism-polymerase chain reaction method. Allelic frequency, haplotype analyses, and linkage disequilibrium were calculated. The odds ratio was calculated. The linear regression model was used to analysis of interleukin (IL)-17A, IL-17F, and IL-6 single-nucleotide polymorphism genotypes in HIV patients with and without toxoplasmosis. RESULTS: In total, 95 tested'patients (28.4%) were positive for toxoplasmosis. The risk of toxoplasma infection in the current study did not correlate with IL-17 and IL-6 polymorphism and the risk of contracting toxoplasma was also not significantly correlated in this study. There was no association between the frequency of alleles and the risk of toxoplasma infection in IL-17 haplotype analysis. CONCLUSION: The findings of this study revealed that there were significant differences in the serum levels of IL-6 and IL-17A, but not IL-17F, between the case and control groups in various genetic models. However, these polymorphisms did not show a significant relationship with toxoplasma infection in HIV-positive patients. This study represents the first investigation in Iran to explore the role of IL-6 and IL-17 polymorphisms in toxoplasma infection among HIV-positive patients.

Targeted Delivery of Anticancer Drug Loaded Charged PLGA Polymeric Nanoparticles Using Electrostatic Field.

Pure positive electrostatic charges (PPECs) show suppressive effect on the proliferation and metabolism of invasive cancer cells without affecting normal tissues. PPECs are used for the delivery of drug-loaded polymeric nanoparticles (DLNs) capped with negatively charged poly(lactide-co-glycolide) (PLGA) and Poly(vinyl-alcohol) PVA into the tumor site of mouse models. The charged patch is installed on top of the skin in the mouse models' tumor region, and the controlled selective release of the drug is assayed by biochemical, radiological, and histological experiments on both tumorized models and normal rats' livers. It is found that DLNs synthesized by PLGA show great attraction to PPECs due to their stable negative charges, which would not degrade immediately in blood. The burst and drug release after less than 48h of this synthesized DLNs are 10% and 50%, respectively. These compounds can deliver the loaded-drug into the tumor site with the assistance of PPECs, and the targeted-retarded release will take place. Hence, local therapy can be achieved with much lower drug concentration (conventional chemotherapy [2 mg kg-1 ] versus DLNs-based chemotherapy [0.75 mg kg-1 ]) with negligible side effects in non-targeted organs. PPECs have many potential clinical applications for advanced-targeted chemotherapy with the lowest discernible side effects.

A Comprehensive Review of the Current Research Status of Biodegradable Zinc Alloys and Composites for Biomedical Applications.

Zinc (Zn)-based biodegradable materials show moderate degradation rates in comparison with other biodegradable materials (Fe and Mg). Biocompatibility and non-toxicity also make them a viable option for implant applications. Furthermore, Pure Zn has poor mechanical behavior, with a tensile strength of around 100-150 MPa and an elongation of 0.3-2%, which is far from reaching the strength required as an orthopedic implant material (tensile strength is more than 300 MPa, elongation more than 15%). Alloy and composite fabrication have proven to be excellent ways to improve the mechanical performance of Zn. Therefore, their alloys and composites have emerged as an innovative category of biodegradable materials. This paper summarizes the most important recent research results on the mechanical and biological characteristics of biodegradable Zn-based implants for orthopedic applications and the most commonly added components in Zn alloys and composites.

Bredigite-CNTs Reinforced Mg-Zn Bio-Composites to Enhance the Mechanical and Biological Properties for Biomedical Applications.

Magnesium (Mg) and its compounds have been investigated as biodegradable metals for bone implants. However, high corrosion rates and low bioactivity that cause loss of mechanical properties are factors that have limited their biomedical applications. The purpose of this work is to remedy the weaknesses of the Mg-Zn (MZ) alloy matrix. For this purpose, we have synthesized Mg-based composites with different concentrations of bredigite (Br; Ca7MgSi4O16)-carbon nanotubes (CNTs) using mechanical alloying and semi-powder metallurgy processes with spark plasma sintering. Then, we studied the effect of the simultaneous addition of Br-CNTs on in vitro degradation, as well as its effect on the composites' mechanical and antibacterial properties. Increases of 57% and 72% respectively were observed in the microhardness and compressive strength of the MZ/Br-CNTs composite in comparison to the MZ alloy. In addition, the rate of degradation of Mg-based composites in simulated body fluids (SBF) was almost 2 times lower. An assessment of antibacterial behavior disclosed that the simultaneous adding of Br-CNTs to Mg can meaningfully prevent the growth and invasion of E. coli and S. aureus. These research findings demonstrate the potential application of MZ/Br-CNTs composites to implants and the treatment of bone infections.

EVs vs. EVs: MSCs and Tregs as a source of invisible possibilities.

Extracellular vesicles (EVs) are produced by various cells and exist in most biological fluids. They play an important role in cell-cell signaling, immune response, and tumor metastasis, and also have theranostic potential. They deliver many functional biomolecules, including DNA, microRNAs (miRNA), messenger RNA (mRNA), long non-coding RNA (lncRNA), lipids, and proteins, thus affecting different physiological processes in target cells. Decreased immunogenicity compared to liposomes or viral vectors and the ability to cross through physiological barriers such as the blood-brain barrier make them an attractive and innovative option as diagnostic biomarkers and therapeutic carriers. Here, we highlighted two types of cells that can produce functional EVs, namely, mesenchymal stem/stromal cells (MSCs) and regulatory T cells (Tregs), discussing MSC/Treg-derived EV-based therapies for some specific diseases including acute respiratory distress syndrome (ARDS), autoimmune diseases, and cancer.

HNF4α is possibly the missing link between epithelial-mesenchymal transition and Warburg effect during hepatocarcinogenesis.

Hepatocellular carcinoma (HCC) is a heterogeneous, late-diagnosed, and highly recurrent malignancy that often affects the whole body's metabolism. Finding certain theranostic molecules that can address current concerns simultaneously is one of the priorities in HCC management. In this study, performing protein-protein interaction network analysis proposed hepatocyte nuclear factor 4 alpha (HNF4α) as a hub protein, associating epithelial-mesenchymal transition (EMT) to reprogrammed cancer metabolism, formerly known as the Warburg effect. Both phenomena improved the compensation of cancerous cells in competitive conditions. Mounting evidence has demonstrated that HNF4α is commonly downregulated and serves as a tumor suppressor in the HCC. Enhancing the HNF4α mRNA translation through a specific synthetic antisense long non-coding RNA, profoundly affects both EMT and onco-metabolic modules in HCC cells. HNF4α overexpression decreased featured mesenchymal transcription factors and improved hepatocytic function, decelerated glycolysis, accelerated gluconeogenesis, and improved dysregulated cholesterol metabolism. Moreover, HNF4α overexpression inhibited the migration, invasion, and proliferation of HCC cells and decreased metastasis rate and tumor growth in xenografted nude mice. Our findings suggest a central regulatory role for HNF4α through its broad access to a wide variety of gene promoters involved in EMT and the Warburg effect in human hepatocytes. This essential impact indicates that HNF4α may be a potential target for HCC treatment.

The effect of Co-encapsulated GNPs-CNTs nanofillers on mechanical properties, degradation and antibacterial behavior of Mg-based composite.

Magnesium (Mg)-based composites, as one group of the biodegradable materials, enjoy high biodegradability, biocompatibility, and non-toxicity making them a great option for implant applications. In this paper, by the semi powder metallurgy (SPM) technique, the graphene nano-platelets (GNPs) and carbon nanotubes (CNTs) nanosystems, as reinforcements, are dispersed homogenously in the Mg-Zn (MZ) alloy matrix. Subsequently, the composite is successfully produced employing the spark plasma sintering (SPS) process. Compared to the unreinforced MZ sample, GNPs + CNTs mixture reinforced composite exhibits higher compressive strength (∼75%). Notably, adding only 1 wt % of GNPs + CNTs to the MZ matrix reduces the rate of the degradation in the Mg-based composite by almost 2- fold. Examining the antibacterial activity demonstrate that the incorporation of GNPs + CNTs into the Mg-based matrix is likely to prevent the infiltration and development of Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) significantly. While the MTT with 0.5 and 1 wt % GNPs + CNTs does not demonstrate cytotoxicity to the MG63 cells, the excessive GNPs + CNTs results in a certain degree of poisonousness. In general, the findings of the present research attest to the viable application of MZ/GNPs + CNTs composites for implants as well as bone infection treatment.

Investigation of job satisfaction amongst voluntary, counseling and testing centers and health centers in Iran.

BACKGROUND: Job satisfaction is the persons' feeling about their job and if personnel have not good feel to his work, can destroy all plans, intentionally or unintentionally. The present research aims to investigate and compare job satisfaction in the employees and therapists of Voluntary, Counseling and Testing Centers versus Health centers in 9 provinces of Iran. METHODS: All employees of Voluntary, Counseling and Testing Centers were included from Fars, Bushehr, Tehran, Isfahan, South Khorasan, Kurdistan, Kermanshah, Kerman, and Yazd provinces as case group and 103 staffs of similar Health centers selected with the same ratio as the staffs of Voluntary, Counseling and Testing Centers as control samples and answered to Minnesota Satisfaction Questionnaire (MSQ). RESULTS: 50.5% of Health centers employees and 54% of Voluntary, Counseling and Testing Centers employees had high job satisfaction. The highest satisfaction levels were reported in Fars and Kurdistan provinces and the lowest satisfaction levels were reported in Kermanshah and Bushehr. CONCLUSION: According to the findings, in the Iranian treatment centers, the employees' satisfaction were at the same level regardless of their position and workplace. Also, the eastern and western regions of the country reported higher satisfaction score than the southern and central regions.

Conjugated Linoleic Acid Treatment Attenuates Cancerous features in Hepatocellular Carcinoma Cells.

Background: A growing number of hepatocellular carcinoma (HCC), and recurrence frequency recently have drawn researchers' attention to alternative approaches. The concept of differentiation therapies (DT) relies on inducing differentiation in HCC cells in order to inhibit recurrence and metastasis. Hepatocyte nuclear factor 4 alpha (HNF4α) is the key hepatogenesis transcription factor and its upregulation may decrease the invasiveness of cancerous cells by suppressing epithelial-mesenchymal transition (EMT). This study aimed to evaluate the effect of conjugated linoleic acid (CLA) treatment, natural ligand of HNF4α, on the proliferation, migration, and invasion capacities of HCC cells in vitro. Materials and Method. Sk-Hep-1 and Hep-3B cells were treated with different doses of CLA or BIM5078 [1-(2'-chloro-5'-nitrobenzenesulfonyl)-2-methylbenzimidazole], an HNF4α antagonist. The expression levels of HNF4a and EMT related genes were evaluated and associated to hepatocytic functionalities, migration, and colony formation capacities, as well as to viability and proliferation rate of HCC cells. Results: In both HCC lines, CLA treatment induced HNF4α expression in parallel to significantly decreased EMT marker levels, migration, colony formation capacity, and proliferation rate, whereas BIM5078 treatment resulted in the opposite effects. Moreover, CLA supplementation also upregulated ALB, ZO1, and HNF4α proteins as well as glycogen storage capacity in the treated HCC cells. Conclusion: CLA treatment can induce a remarkable hepatocytic differentiation in HCC cells and attenuates cancerous features. This could be as a result of HNF4a induction and EMT inhibition.

Establishing minimal clinically important difference for effectiveness of corrective exercises on craniovertebral and shoulder angles among students with forward head posture: a clinical trial study.

BACKGROUND: Previous studies have addressed the effects of different exercises and modalities on forward head posture (FHP), but the minimal clinically important difference (MCID) of the effect of exercises on FHP remains unclear. Therefore, this study aimed to investigate the effects of selective corrective exercises (SCEs) on the craniovertebral angle (CVA) and shoulder angle (SA) in students with FHP and to establish MCID for these angles. METHODS: In this randomized clinical trial study, a total of 103 second-grade male students with FHP were enrolled. Participants were randomly assigned to experimental and control groups. CVA and SA of participants were measured before and after the 8-week selective corrective exercise program (including strengthening and stretching exercises). The photogrammetric method was used to measure CVA and SA. MCID value was calculated for CVA and SA using the distribution method. RESULTS: The results showed that there was a significant difference between the experimental and control groups in terms of CVA (F = 89.04, P = 0.005, Effect size = 0.47) and SA (F = 18.83, P = 0.005, Effect size = 0.16). After eight weeks of selective corrective exercises, the MCID values of CVA and SA were 1.40° and 1.34°, respectively. CONCLUSION: This study revealed that the selective corrective exercises might lead to postural correction of students having FHP problem. Results further indicated that a corrective exercise program would be considered beneficial if it increased CVA and SA values at least 1.40 and 1.34 degrees, respectively.

3D or not 3D: a guide to assess cell viability in 3D cell systems.

Cell viability is the primary integrative parameter used for various purposes, particularly when fabricating tissue equivalents (e.g., using bioprinting or scaffolding techniques), optimizing conditions to cultivate cells, testing chemicals, drugs, and biomaterials, etc. Most of the conventional methods were originally designed for a monolayer (2D) culture; however, 2D approaches fail to adequately assess a tissue-engineered construct's viability and drug effects and recapitulate the host-pathogen interactions and infectivity. This study aims at revealing the influence of particular 3D cell systems' parameters such as the components' concentration, gel thickness, cell density, etc. on the cell viability and applicability of standard assays. Here, we present an approach to achieving adequate and reproducible results on the cell viability in 3D collagen- and fibrin-based systems using the Live/Dead, AlamarBlue, and PicoGreen assays. Our results have demonstrated that a routine precise analysis of 3D systems should be performed using a combination of at least three methods based on different cell properties, e.g. the metabolic activity, proliferative capacity, morphology, etc.

Organoids in modelling infectious diseases.

Approaches based on animal and two-dimensional (2D) cell culture models cannot ensure reliable results in modeling novel pathogens or in drug testing in the short term; therefore, there is rising interest in platforms such as organoids. To develop a toolbox that can be used successfully to overcome current issues in modeling various infections, it is essential to provide a framework of recent achievements in applying organoids. Organoids have been used to study viruses, bacteria, and protists that cause, for example, respiratory, gastrointestinal, and liver diseases. Their future as models of infection will be associated with improvements in system complexity, including abilities to model tissue structure, a dynamic microenvironment, and coinfection. Teaser. Organoids are a flexible tool for modelling viral, bacterial and protist infections. They can provide fast and reliable information on the biology of pathogens and in drug screening, and thus have become essential in combatting emerging infectious diseases.

Organoids: a novel modality in disease modeling.

Limitations of monolayer culture conditions have motivated scientists to explore new models that can recapitulate the architecture and function of human organs more accurately. Recent advances in the improvement of protocols have resulted in establishing three-dimensional (3D) organ-like architectures called 'organoids' that can display the characteristics of their corresponding real organs, including morphological features, functional activities, and personalized responses to specific pathogens. We discuss different organoid-based 3D models herein, which are classified based on their original germinal layer. Studies of organoids simulating the complexity of real tissues could provide novel platforms and opportunities for generating practical knowledge along with preclinical studies, including drug screening, toxicology, and molecular pathophysiology of diseases. This paper also outlines the key challenges, advantages, and prospects of current organoid systems.

Tissue-Specific Microparticles Improve Organoid Microenvironment for Efficient Maturation of Pluripotent Stem-Cell-Derived Hepatocytes.

Liver organoids (LOs) are receiving considerable attention for their potential use in drug screening, disease modeling, and transplantable constructs. Hepatocytes, as the key component of LOs, are isolated from the liver or differentiated from pluripotent stem cells (PSCs). PSC-derived hepatocytes are preferable because of their availability and scalability. However, efficient maturation of the PSC-derived hepatocytes towards functional units in LOs remains a challenging subject. The incorporation of cell-sized microparticles (MPs) derived from liver extracellular matrix (ECM), could provide an enriched tissue-specific microenvironment for further maturation of hepatocytes inside the LOs. In the present study, the MPs were fabricated by chemical cross-linking of a water-in-oil dispersion of digested decellularized sheep liver. These MPs were mixed with human PSC-derived hepatic endoderm, human umbilical vein endothelial cells, and mesenchymal stromal cells to produce homogenous bioengineered LOs (BLOs). This approach led to the improvement of hepatocyte-like cells in terms of gene expression and function, CYP activities, albumin secretion, and metabolism of xenobiotics. The intraperitoneal transplantation of BLOs in an acute liver injury mouse model led to an enhancement in survival rate. Furthermore, efficient hepatic maturation was demonstrated after ex ovo transplantation. In conclusion, the incorporation of cell-sized tissue-specific MPs in BLOs improved the maturation of human PSC-derived hepatocyte-like cells compared to LOs. This approach provides a versatile strategy to produce functional organoids from different tissues and offers a novel tool for biomedical applications.

Coping styles in HIV positives and HIV negatives.

BACKGROUND: Choosing the most useful and versatile way to solve one's personal and social problems is one of the most important choices in individual life. The aim of this study was to compare the coping styles of people living with Human immunodeficiency virus positive and negative. METHODS: This is a Cross-sectional study that accomplished in Shiraz Behavioural Disease Counselling Centre in 2019 and 2020. For this purpose, in the first phase, 40 HIV+ and 40 HIV- patients were randomly selected to answer the questionnaire of dealing with the stressful conditions of Andler and Parker. In the second phase, the same questionnaire was filled out along with a reality distortion questionnaire from similar individuals (40 HIV+ and 40 HIV-). RESULTS: 92% of the HIV population in this study was between 15 and 55 years and 8% was upper than 55 years. 90% of them had no university degree. Among all, 47.5% of them were, 48.5% were self-employed and 49% of them were infected sexually. The results showed that in the first stage there was a significant relationship between marital status and the chances of getting the disease in people, and after controlling the demographic factors, coping styles did not show a significant effect on the disease. In the second stage, the factors of age, sex, education, and marital status had significant effects on people living with HIV, but the effect of coping styles on people with HIV was not significant (P < 0.05). CONCLUSION: Therefore, it can be concluded that demographic factors more than coping styles can affect the chances of high-risk behaviours; so, what is identified and measured as a coping style in people in the process that leads to the manifestation of high-risk behaviours or healthy behaviour does not matter much. It should be noted that the reason for rejecting the hypotheses of this study could be the effect of cultural and social factors of Iranian society.

Tissue Engineering in Liver Regenerative Medicine: Insights into Novel Translational Technologies.

Organ and tissue shortage are known as a crucially important public health problem as unfortunately a small percentage of patients receive transplants. In the context of emerging regenerative medicine, researchers are trying to regenerate and replace different organs and tissues such as the liver, heart, skin, and kidney. Liver tissue engineering (TE) enables us to reproduce and restore liver functions, fully or partially, which could be used in the treatment of acute or chronic liver disorders and/or generate an appropriate functional organ which can be transplanted or employed as an extracorporeal device. In this regard, a variety of techniques (e.g., fabrication technologies, cell-based technologies, microfluidic systems and, extracorporeal liver devices) could be applied in tissue engineering in liver regenerative medicine. Common TE techniques are based on allocating stem cell-derived hepatocyte-like cells or primary hepatocytes within a three-dimensional structure which leads to the improvement of their survival rate and functional phenotype. Taken together, new findings indicated that developing liver tissue engineering-based techniques could pave the way for better treatment of liver-related disorders. Herein, we summarized novel technologies used in liver regenerative medicine and their future applications in clinical settings.