ABSTRACT
Background: There are more than 1100 different pathogenic variants in the phenylalanine hydroxylase (PAH) gene that are responsible for phenylketonuria (PKU) diseases, and the spectrum of these mutations varies in different ethnic groups. The aim of the present study was to identify the frequency of pathogenic variants in all 13 exons of the PAH gene among patients with PKU in Mazandaran and Golestan provinces in the north of Iran. Methods: Forty unrelated PKU patients from Mazandaran and Golestan provinces were enrolled in the study. Genomic DNA was extracted from leukocytes using a Qiagen DNA extraction kit and polymerase chain reaction - restriction fragment length polymorphism (PCR-RFLP), and Sanger sequencing methods were applied to detect the variants. In the case of new variants, the InterVar online tool (PMID: 28132688) was used to classify the variants. Results: Twenty-one different pathogenic variants were observed among the 40 investigated patients. The c.106611G>A variant had the highest frequency (27.5%) in the region, and the c.168+5G>C, c.473G>A, and c.782 G>A variants were the other most frequent mutations with allelic frequencies of 7.5, 5, and 5%, respectively. Three novel pathogenic variants including c.773T>G, c.878 T>C, and c. 1245del variants were observed among the investigated patients. Conclusions: The introduction of pathogenic variants in the PAH gene in each ethnic group provides valuable data regarding the understanding of the pathogenesis of the disease and can be helpful for prenatal diagnosis programs.
ABSTRACT
Up to now, more than 300 pathogenic variants have been identified in the ß-globin gene, some of which are categorized as silent mutations that do not change the hematological indices. In the present study, our aim is to introduce the first report of a case with thalassemia intermedia with coinheritance of the c.315 + 1 G > A pathogenic variant and a silent variant (HBB: c.-19 G > C) that was missed during the screening program. Multiplex-Gap-PCR and Sanger sequencing methods were applied to identify α- and ß-globin gene mutations in a 26-year-old male subject with diagnosis of thalassemia. The identified mutations were also checked on the parent's sample. The CBC and capillary electrophoresis tests were performed on the parent's blood samples. The case was compound heterozygote for the c.315 + 1 G > A and c.-19 G > C (rs1239893012) variants. The subject's mother carried the c.-19 G > C variant in the ß-globin gene while her CBC and electrophoresis test results showed a normal pattern. Silent mutations are susceptible to being missed during premarital screening of ß-thalassemia carriers, and the c.-19 G > C variant is recommended to be classified as a pathogenic variant in the ß-globin gene.
ABSTRACT
BACKGROUND: Sulfur mustard (SM) is a toxic gas that causes chronic inflammation and oxidative stress leading to cell senescence. This study aimed to evaluate two indicators of biological aging (i.e., serum lipofuscin level and leukocyte telomere length) and assess their relationship based on the severity of SM exposure in the long term. METHODS: The study was performed on two groups of male participants. 1) SM-exposed group (exposed to SM once in 1987), 73 volunteers. 2) Non-exposed group, 16 healthy volunteers. The SM-exposed group was categorized into three subgroups based on the severity of SM exposure and body damage (asymptom, mild, and severe). The blood sample was prepared from members of each group. The serum lipofuscin, TGF-ß, malondialdehyde (MDA), c-reactive protein (CRP), and leukocyte telomere length (TL) were measured in all participants. RESULTS: The MDA level was increased in the SM-exposed group (mean = 39.6 µM, SD = 16.5) compared to the non-exposed group (mean = 21.1 µM, SD = 10.3) (P < 0.05). The CRP level was also increased in the SM-exposed group (mean = 5.12 mg/l, SD = 3.36) compared to the non-exposed group (mean = 3.51 mg/l, SD = 1.21), while the TGF-ß level was decreased (P < 0.05) in the SM-exposed group (mean = 52.6 pg/ml, SD = 18.7) compared to the non-exposed group (mean = 68.9 pg/ml, SD = 13.8). The relative TL was shorter in the SM-exposed group (mean = 0.40, SD = 0.28) than in the non-exposed group (mean = 2.25, SD = 1.41) (P < 0.05). The lipofuscin level was higher in the total SM-exposed group (mean = 1.44 ng/ml, SD = 0.685) than in the non-exposed group (mean = 0.88 ng/ml, SD = 0.449) (P < 0.05). The MDA and CRP levels were increased in the SM-exposed subgroups of asymptom, mild, and severe than the non-exposed group, while TGF-ß level and TL were decreased in those subgroups. The lipofuscin level was higher in the SM-exposed subgroups of mild and severe than in the non-exposed group. The regression analysis determined a negative correlation between lipofuscin level and TL. The lipofuscin/TL ratio was higher in the total SM-exposed group (mean = 6.36, SD = 5.342) than in the non-exposed group (mean = 0.51, SD=0.389). This ratio was also higher in the SM-exposed subgroups of asymptom, mild, and severe than in the non-exposed group. The lipofuscin/TL ratio did not differ between mild and severe subgroups. CONCLUSION: The delayed toxicity of SM is associated with chronic oxidative stress, continuous inflammatory stimulation, increased lipofuscin, and telomere shortening. Future studies are needed to verify the suitability of serum lipofuscin to telomere length ratio in determining the severity of SM toxicity.
Subject(s)
Chemical Warfare Agents , Mustard Gas , Veterans , Humans , Male , Mustard Gas/toxicity , Chemical Warfare Agents/toxicity , Telomere Shortening , Lipofuscin , Leukocytes , Cellular Senescence , Transforming Growth Factor betaABSTRACT
Due to the unique affinity of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to the angiotensin-converting enzyme 2 (ACE2) receptor in patients, the foremost recent evidence indicated that ACE1 and ACE2 polymorphisms could affect the susceptibility of individuals to SARS-CoV-2 infection and also the disease outcome. Here, we aimed to assess the possible association between two polymorphisms and the severity of disease in patients. In the present study, 146 patients with COVID-19 who were admitted to the Mazandaran University of Medical Sciences hospitals between March 2020 and July 2020 were enrolled in this case-control study. The patients were divided into four groups based on clinical symptoms and severity of the diseases (mild, moderate, severe, and critical). After DNA extraction, the ACE gene I/D polymorphism (rs4646994) and ACE2 gene polymorphism (rs2285666) were genotyped using Gap-PCR and PCR-RFLP techniques, respectively. Then, five samples from each obtained genotype were confirmed by Sanger sequencing technique. Data were analyzed with SAS software version 9.1 using appropriate statistical procedures. The ACE gene I/D polymorphism (rs4646994) genotypes were classified into three types: I/I, I/D, and D/D. Our finding indicated that the prevalence of ACE1 D/D genotype was significantly higher in severe and critical COVID-19 patients (P = 0.0016). Additionally, the analysis revealed a remarkable association between rs4646994 SNP and the HB and ESRI levels in patients (P < 0.05). Although the ACE2 rs2285666 SNP was not related to the severity of disease, this variant was significantly associated with ALT, ESRI, and P. These results provide preliminary evidence of a genetic association between the ACE-D/D genotype and the D allele of ACE1 genotype and the disease severity. Therefore, our findings might be useful for identifying the susceptible population groups for COVID-19 therapy.
Subject(s)
Angiotensin-Converting Enzyme 2 , COVID-19 , Peptidyl-Dipeptidase A , Humans , Angiotensin-Converting Enzyme 2/genetics , Case-Control Studies , COVID-19/genetics , Peptidyl-Dipeptidase A/genetics , Polymorphism, Genetic , SARS-CoV-2/physiologyABSTRACT
SQSTM1 gene encodes a protein called p62 that acts as an autophagy receptor in the degradation of protein molecules. A homozygous deletion variant that changes the frame shift in the SQSTM1 gene named c.790 Del A .T was detected in case childhood onset and progressive neurodegeneration with ataxia, and gaze palsy.
ABSTRACT
Sulfur mustard (SM) is a toxic gas that has been used as a chemical weapon in wars. After many years, SM-exposed people are still suffering from its side effects such as biological and premature aging. This study was aimed to evaluate biological aging rate via involving biological health scoring (BHS), relative telomere length (TL) and different physical/social variables i.e. marital and smoking statuses, body mass index, salary and educational levels. BHS was calculated according to measurement of 18 biomarkers related to function of four physiological systems (endocrine, inflammatory, cardiovascular and metabolic systems) and two organs (liver and kidney). The volunteers were 442 individuals exposed to SM gas in 1987 and 119 healthy individuals as non-exposed group. Each group was divided based on leukocyte relative TL (short, intermediate and long). Our data showed an inverse correlation between BHS and relative TL in two groups. The BHS was significantly higher in SM-exposed group than non-exposed group, especially in the participants with short and intermediate TL. The BHS had also a positive correlation with smoking and BMI parameters, and a negative correlation with salary and educational levels in the participants with shorter telomeres; and SM strengthened these correlations in the shorter telomeres. It is concluded that the higher BHS along with shorter relative TL that are indices for lower health quality and biological aging, could be used in the health evaluation of non- and SM-exposed people; and involving of BHS, TL and physical/social covariates could be useful to make this evaluation more accurate.
Subject(s)
Mustard Gas , Veterans , Aging , Humans , Mustard Gas/toxicity , Mustard Plant , Telomere , Telomere ShorteningABSTRACT
Early-life environmental conditions affect offspring's development. Maternal deprivation (MD) can induce persistent changes that give rise to neuropsychiatric diseases including substance abuse disorders. However, long-lasting mechanisms that determine vulnerability to drug addiction remain unknown. We hypothesized that MD could induce changes in Opioid system, HPA (hypothalamic-pituitary-adrenal) axis, and BDNF (brain-derived neurotrophic factor), so may be involved in the drug abuse in later life. Male offspring of Wistar rats (n = 8 per group) were subjected to 3 h of daily MD during postnatal days 1-14. In adulthood, morphine-induced CPP (conditioned place preference) was investigated using two doses of morphine (3 and 5 mg/kg). Serum corticosterone level was measured by ELISA method. The expression level of genes in selected brain regions (hippocampus, prefrontal cortex, and nucleus accumbens) was determined by qPCR (quantitative PCR). A greater morphine-induced CPP was observed in MD rats with 3 and 5 mg/kg morphine compared to controls. MD group had a higher corticosterone level. A significant decrease was observed in the expression of BDNF gene (in all of the selected brain regions) and GR (glucocorticoid receptor) gene (in the hippocampus and nucleus accumbens) in MD rats. Also, a significant increase in the expression of µ Opioid receptor (in all of the selected brain regions) and κ Opioid receptor (in the prefrontal cortex and nucleus accumbens) was observed in MD rats. Our results suggest that MD induces alterations in the HPA axis function, BDNF level, and Opioid receptors system that enhance vulnerability to morphine at adulthood.
Subject(s)
Morphine , Nucleus Accumbens , Animals , Male , Rats , Brain/metabolism , Hippocampus/metabolism , Hypothalamo-Hypophyseal System/metabolism , Maternal Deprivation , Morphine/metabolism , Morphine/pharmacology , Pituitary-Adrenal System/metabolism , Prefrontal Cortex , Rats, Wistar , Receptors, Opioid/metabolismABSTRACT
Among the many polymers introduced for bone tissue engineering, natural polymers have more advantages due to their high biocompatibility and biodegradability, despite their low mechanical properties. Herein, gelatin nanofibers with and without magnesium oxide (MgO) and graphene oxide (GO) nanoparticles were fabricated by electrospinning. The fabricated gelatin and gelatin/GO/MgO nanofibers were examined using scanning electron microscopy, protein adsorption, cell attachment and viability assays. The results revealed that biological behaviours of the gelatin nanofibers significantly improved while incorporated with MgO and GO nanoparticles. In the following, osteosupportive capacity of the fabricated scaffolds was investigated by Alizarin-red staining, alkaline phosphatase activity, and calcium content, and bone-related gene and protein assays. The results revealed that the highest osteogenic differentiation potential of human-induced pluripotent stem cells (hiPSCs) was detected while these cells were cultured on the gelatin/GO/MgO nanofibers. However, these makers in the hiPSCs cultured on the gelatin nanofibers were also significantly increased in comparison with the cells cultured on the tissue culture plates as a control. In conclusion, the results revealed that predictable disadvantages in gelatin nanofibers can be greatly improved by the addition of MgO and GO nanoparticles, and the resulting composite scaffold could be a potential candidate for use in bone tissue engineering.
Subject(s)
Induced Pluripotent Stem Cells , Nanofibers , Osteogenesis , Cell Differentiation , Cell Proliferation , Gelatin , Graphite , Humans , Magnesium Oxide , Tissue ScaffoldsABSTRACT
Stem cells from umbilical cord blood (UCB) are able to proliferate and differentiate into various somatic cell types. Thereby, they are considered as one of the attractive stem cell sources in tissue engineering and regenerative medicine. However, the limited number of hematopoietic CD 133+ stem cells in UCB restricted the clinical application of such stem cells. This study was aimed to expand CD 133+ stem cells derived from UCB on a 3D silk scaffold. UCB133+ stem cells were extracted using Magnetic cell sorting (MACS) and characterized by flow cytometry. Isolated cells were seeded on a fabricated electrospun silk scaffold and cultured for 7 days. The real-time PCR, cell counting, colony-forming assay, and MTT assay were performed to evaluate the expansion and homing of stem cells. The results showed a higher expression of CXCR4 gene, the number of cultured stem cells, and colony-forming units in the 3D silk scaffold group after 7 days when compared to the tissue culture plate. Moreover, higher viability and proliferation of stem cells were seen in cells cultured on silk scaffold. It seems electrospun silk scaffold could be used as a suitable substrate for UCB CD 133+ stem cell expansion.
Subject(s)
AC133 Antigen/metabolism , Fetal Blood/cytology , Hematopoietic Stem Cells/cytology , Nanofibers , Cell Culture Techniques/methods , Cell Proliferation , Cell Separation/methods , Cells, Cultured , Colony-Forming Units Assay , Hematopoietic Stem Cells/metabolism , Humans , Microscopy, Electron, Scanning , Nanofibers/chemistry , Receptors, CXCR4/genetics , Receptors, CXCR4/metabolism , Silk/chemistry , Tissue Scaffolds/chemistryABSTRACT
BACKGROUND: Mustard gas as a chemical weapon has been used in wars and its long-term side effects are substantial in the human body. This study was aimed to apply an extension of allostatic load, known as synthetic biological health score (BHS), including the wear-and-tear of four physiological systems (endocrine, inflammatory, cardiovascular and metabolic systems) and two organs (liver and kidney) to estimate biological aging caused by sulfur mustard (SM) gas poisoning. METHODS: The plasma samples were prepared from two following groups of people; 1) 446 individuals exposed to SM gas in 1987. 2) 115 healthy members, at the same range of age and residence, as the non-exposed group. These people were chosen from the same patients' families and have not had any exposure to SM or pulmonary dysfunction. To estimate BHS, 18 blood-derived biomarkers of the mentioned systems and organs were measured and the relative contribution of many social and body parameters across the age groups was explored. RESULTS: It was revealed, in BHS calculation, the cardiovascular system had the most effect. Also, in the SM group, BHS was significantly higher than in the control group. This feature has a positive correlation with physical parameter (BMI) and a negative correlation with social parameters (salary and educational levels). CONCLUSION: The multisystem BHS could be useful in the evaluation of biological aging due to SM exposure. Social (education, good-paying job) and physical (BMI) parameters could influence BHS and the higher BHS indicates the progress of biological aging due to mustard gas.
Subject(s)
Aging/drug effects , Chemical Warfare Agents/toxicity , Mustard Gas/toxicity , Adult , Biomarkers/blood , Case-Control Studies , Chemical Warfare , Humans , Iran , Middle Aged , VeteransABSTRACT
BACKGROUND: Gyrate atrophy is a rare autosomal recessive inherited genetic disease. Progressive deterioration of peripheral night vision and blindness are the foremost clinical manifestations of the disease caused by mutations of ornithine aminotransferase gene. CASE: The presented case was an 18-year-old male referred for a progressive reduction of visual acuity, which started when the subject was 7 years old, blurred vision, and hypotonic muscles. OBSERVATIONS: The findings by liquid chromatography with tandem mass spectrometry and high-performance liquid chromatography methods exhibited a high level of ornithine: 248 µmol/L (reference range: 44-206 µmol/L) and 818 µmol/L (reference: 25-123 µmol/L), respectively. After genetic counseling and conducting further investigation, a novel mutation (c.425-1G>A) in ornithine aminotransferase gene was recognized through whole exome sequencing and the mutation was verified using Sanger sequencing method, which is associated with gyrate atrophy phenotype. CONCLUSION: The exact mechanism of chorioretinal atrophy in hyperornithinemia is not known but the increased ornithine level is the clinical manifestation of gyrate atrophy of choroid and retina, muscle weakness, moderate mental retardation, and low cerebral creatine. Pathogenic variant in the ornithine aminotransferase gene associated with gyrate atrophy, may be beneficial as a biomarker to initial diagnosis and treatment of gyrate atrophy disease.
Subject(s)
Gyrate Atrophy , Adolescent , Atrophy/pathology , Child , Choroid/pathology , Gyrate Atrophy/diagnosis , Gyrate Atrophy/genetics , Humans , Male , Mutation , Ornithine-Oxo-Acid Transaminase/genetics , Retina/pathologyABSTRACT
In the original publication of this article [1], there are two corrections.
ABSTRACT
Objective: The present study was conducted to investigate the effect of Viola odorata extracted syrup on the quality and patterns of sleep in patients with depression or obsessive-compulsive disorder (OCD) as add-on therapy. Design: A pilot double-blind randomized placebo-controlled trial. Settings/Location: Psychiatric Clinic of Imam Hossein Hospital, Tehran, Iran. Subjects: Participants were 16-15 years of age with mild and moderate depression or OCD having insomnia. Interventions: This pilot study was conducted on patients with insomnia divided into two groups with depression (40 patients) or OCD (43 patients). Each group randomly assigned into two arms with the same conditions at baseline. The intervention arm daily received 5 mL V. odorata syrup every 12 h for 4 weeks, and the control arm received 5 mL placebo syrup every 12 h for 4 weeks. None of the participants was deprived of their routine treatment for depression or OCD. Outcome measures: The scores of insomnia symptoms were evaluated using total score of the Pittsburgh Sleep Quality Index (PSQI) and the scores of its components, the depression score using the final Beck depression inventory-II (BDI-II) score, and OCD score using the Yale-Brown Obsessive-Compulsive Scale (YBOCS). Results: The total PSQI score was found to be improved significantly in the intervention arms with depression or OCD (p < 0.001) compared with the corresponding control arms. Significant improvements were also observed in the final mean difference of BDI-II (p = 0.009) and YBOCS (p = 0.001) scores in the intervention arms. Conclusions: V. odorata syrup significantly improved insomnia symptoms and the scores of depression and OCD.
Subject(s)
Depressive Disorder/drug therapy , Obsessive-Compulsive Disorder/drug therapy , Plant Preparations/therapeutic use , Sleep Initiation and Maintenance Disorders/drug therapy , Viola , Adolescent , Adult , Depressive Disorder/complications , Double-Blind Method , Female , Humans , Male , Middle Aged , Obsessive-Compulsive Disorder/complications , Pilot Projects , Sleep Initiation and Maintenance Disorders/etiology , Surveys and Questionnaires , Young AdultABSTRACT
BACKGROUND: Iran's Parliament passed a Law in 2010 to merge the existing health insurance schemes to boost risk pooling. Merging can be challenging as there are differences among health insurance schemes in various aspects. This qualitative prospective policy analysis aims to reveal key challenges and implementation barriers of the policy as introduced in Iran. METHODS: A qualitative study of key informants and documentary review was conducted. Sixty-seven semi-structured face-to-face interviews were conducted, with key informants from relevant stakeholders. Purposive and snowball sampling techniques were used for selecting the interviewees. The related policy documents were also reviewed and analyzed to supplement interviews. Data analysis was conducted through an existing health financing World Bank framework. RESULTS: This study demonstrated that for combining health insurance funds, operational challenges in the following areas should be taken into account: financing mechanisms, population coverage, benefits package, provider engagement, organizational structure, health service delivery and operational processes. It is also important to have adequate cogent reasons to "the justification of the consolidation process" in the given context. When moving towards combining health insurance funds, especially in countries with a purchaser-provider split, it is critical for policy makers to make sure that the health insurance system is aligned with the policies and Stewardship of the broader health care system. CONCLUSIONS: Implementation of major reforms in a health system with fragmented insurance schemes with different target populations, prepayment structures, benefit packages and history of development is inherently difficult, especially when different stakeholders have vetoing powers over the proposed reforms. Solving the differences and operational challenges in the main areas of health insurance system generated in this study may provide a platform for the designing and implementing merging process of social health insurance schemes in Iran and other countries with similar situations.
Subject(s)
Financial Management/organization & administration , Health Policy/legislation & jurisprudence , Insurance, Health/economics , Adult , Aged , Aged, 80 and over , Female , Humans , Insurance, Health/organization & administration , Iran , Male , Middle Aged , Policy Making , Prospective Studies , Qualitative Research , Social Security/organization & administration , Stakeholder Participation/psychologyABSTRACT
INTRODUCTION: Sulfur mustard (SM) is a potent toxic agent that cause local and systemic changes in the human body such as dysregulation of the immunological system. This gas affects different organs such as lungs, skin, eyes and the gastrointestinal tract. METHODS: 128 veterans with SM-induced eye injuries were examined and compared to 31 gender- and age-matched healthy controls. Serum levels of IgM, IgE, IgA, IgG, and IgG subclasses were measured using ELISA method. RESULTS: There was no significant difference in IgM level between two groups with abnormal and normal ocular conditions except for those having bulbar conjunctiva-limbal ischemia and bulbar conjunctiva-hyperemia abnormalities. There were not significant difference in IgA, IgE, and IgG levels between two groups with and without ocular problem also between study groups. IgG1 level in some ocular abnormalities were significantly lower than the healthy control groups. IgG2 level in SM-exposed participants with stromal abnormality was higher in the SM-exposed groups without this problem. IgG2 levels in the exposed group with some ocular problems were significantly increased compared with control. IgG3 level in all patients did not reveal any significant changes compared with the controls except the fundus abnormality. IgG4 level was not significantly different between two groups with normal and abnormal ocular conditions. Nonetheless, IgG4 level in the exposed participants with some ocular abnormalities significantly increased compared with the controls. CONCLUSION: The results showed SM exposure could alter immunoglobulins level compared with healthy controls and the changes of IgG2 and IgG1 levels were associated with some ocular problems.
Subject(s)
Chemical Warfare Agents/toxicity , Eye Injuries/blood , Eye Injuries/chemically induced , Immunoglobulins/blood , Mustard Gas/toxicity , Adult , Environmental Exposure/adverse effects , Eye Injuries/immunology , Female , Humans , Male , Veterans , Young AdultABSTRACT
BACKGROUND: Sulfur mustard (SM) exposure produces extensive systemic and ocular adverse effects on the victims. One of the most important effects is immunological insults that can lead to other organ damages, including the eyes. METHODS: In this descriptive study, 128 SM-exposed veterans with severe eye injury were compared with 31 healthy controls. Tear levels of tumor necrosis factor (TNF)-α and serum concentrations of interleukin (IL)-1α, IL-1ß, IL1Ra, IL-6, TNF-α, granulocyte-macrophage colony-stimulating factor (GM-CSF), and Fas Ligand (FasL) were compared between the two groups. RESULTS: Meibomian gland dysfunction (MGD); tear breakup time (TBUTâ¯<â¯10â³); and conjunctival, limbal, and corneal abnormalities were more frequent among the cases (MS-exposed veterans) than the controls. Ocular involvement was mild in 14.8%, moderate in 24.2%, and severe in 60.9% of the cases. Serum levels of IL-1α and FasL were significantly higher among the cases than among the controls (Pâ¯<â¯0.001 and Pâ¯=â¯0.037, respectively). Also, a significant decrease was observed in serum and tear levels of TNF-α in the cases as compared with controls (Pâ¯<â¯0.001, Pâ¯<â¯0.001, respectively). Serum levels of FasL were significantly higher in cases with severe ocular involvement than in the controls (Pâ¯=â¯0.03). Nonetheless, serum levels of IL-1ß, IL-1Ra, IL-1α/IL-1Ra, and IL-6 were not significantly different between the two groups. CONCLUSION: Serum levels of IL-1α and FasL may cause different ocular surface abnormalities in SM-exposed patients. Lower tear TNF-α concentration may be due to lower serum levels of this cytokine in these patients.
Subject(s)
Chemical Warfare Agents/toxicity , Cytokines/blood , Eye Injuries/blood , Eye Injuries/chemically induced , Fas Ligand Protein/blood , Inflammation Mediators/blood , Mustard Gas/toxicity , Adult , Antigens, CD/blood , Cytokines/immunology , Environmental Exposure/adverse effects , Eye/pathology , Eye Injuries/immunology , Eye Injuries/pathology , Humans , Inflammation Mediators/immunology , Male , Middle Aged , Nitrites/blood , Tears/chemistry , Veterans , Lymphocyte Activation Gene 3 ProteinABSTRACT
Diabetes is one of the most common diseases in the world that is chronic, progressive, and costly, and causes many complications. Common drug therapies are not able to cure it, and pancreas transplantation is not responsive to the high number of patients. The production of the insulin producing cells (IPCs) from the stem cells in the laboratory and their transplantation to the patient's body is one of the most promising new approaches. In this study, the differentiation potential of the induced pluripotent stem cells (iPSCs) and mesenchymal stem cells (MSCs) into IPCs was compared to each other while cultured on poly(lactic-co-glycolic) acid (PLGA)/polyethylene glycol (PEG) nanofibrous scaffold as a 3D substrate and tissue culture polystyrene (TCPS) as a 2D substrate. Although the expression level of the insulin, Glut2 and pdx-1 genes in stem cells cultured on 3D substrate was significantly higher than the stem cells cultured on 2D substrate, the highest expression level of these genes was detected in the iPSCs cultured on PLGA-PEG. Insulin and C-peptide secretions from differentiated cells were also investigated and the results showed that secretions in cultured iPSCs on the PLGA-PEG were significantly higher than cultured iPSCs on the TCPS and cultured MSCs on both PLGA-PEG and TCPS. In addition, insulin protein was also expressed in the cultured iPSCs on the PLGA-PEG significantly higher than cultured MSCs on the PLGA-PEG. It can be concluded that differentiation potential of iPSCs into IPCs is significantly higher than human MSCs at both 2D and 3D culture systems.
Subject(s)
Cell Culture Techniques/instrumentation , Cell Differentiation/physiology , Induced Pluripotent Stem Cells/physiology , Insulin/metabolism , Mesenchymal Stem Cells/physiology , C-Peptide/metabolism , Cell Culture Techniques/methods , Humans , Real-Time Polymerase Chain Reaction/methods , Reverse Transcriptase Polymerase Chain Reaction/methodsABSTRACT
BACKGROUND: Studies indicate that food restriction (FR) reinforces the effects of morphine. The exact mechanisms by which FR influences the reward circuitry of morphine have not yet been determined. OBJECTIVES: We hypothesized that the effects of FR on the oxytocin (OXT) system and HPA axis can be associated with substance abuse disorders. In this study, the serum levels of OXT and corticosterone, and the expression of OXT/OXT receptor (OXTR), glucocorticoid receptor (GR), and brain-derived neurotrophic factor (BDNF) in the hippocampus, prefrontal cortex, and nucleus accumbens were investigated in an FR model. METHODS: First, the male rats (n = 8 per group) were subjected to FR for 3 weeks. Then, morphine-induced conditioned place preference (CPP) was observed using two doses of morphine (3 and 5 mg/kg). The serum concentrations of corticosterone and OXT were determined by ELISA and the expression of genes was examined by qPCR. RESULTS: FR induced an enhanced preference in the animals for the 5 mg/kg dose of morphine compared to the controls. Serum corticosterone levels increased after FR but OXT levels decreased. Meanwhile, FR actuated downregulation of GR, BDNF, and OXT genes, while inducing the overexpression of OXTR. CONCLUSION: We propose the inclusion of OXT and OXTR alterations in the enhancement of morphine-induced CPP and addiction vulnerability following FR. Moreover, we conclude that altered BDNF levels and HPA axis activity may be the mechanisms involved in the effects of FR on morphine-induced behavior.
Subject(s)
Caloric Restriction , Conditioning, Psychological/drug effects , Morphine/pharmacology , Oxytocin/metabolism , Receptors, Oxytocin/metabolism , Animals , Brain-Derived Neurotrophic Factor , Hippocampus/metabolism , Hypothalamo-Hypophyseal System/metabolism , Male , Pituitary-Adrenal System/metabolism , Prefrontal Cortex/metabolism , Rats , Reinforcement, Psychology , RewardABSTRACT
Osteoarthritis (OA) as the most frequent form of knee arthritis is one of the most annoying complications amongst old peoples. There are different pharmacological and non-pharmacological remedies which could be applied for treatment of knee OA. It's while, significant side effects mostly in patients who are older are the dangerous limiting factors. Integrative, supplementary, traditional remedies have been applied from long time ago in treatment of such chronic diseases like OA. Various topical and oral remedies have been presented in treatment of OA worldwide. In spite of the fact there are multiple remedies for reduction symptoms of patients who suffer from disorders and related inabilities which could enhance their life quality. Remedies which have been applied for a long time for treatment of OA have newly discovered to induce injury to some patients. On the other side, additional knowledge about alternative and supplementary remedies is a main way for enhancing health of patients who suffer from OA disorders. Zingiber zerumbet (Z. zerumbeton) is a kind of herb of the ginger family and is a natural compound with various biomedical characteristics like anti-proliferative, anti-inflammatory, and antioxidant effect. However, Z. zerumbet could be applied for reduction of OA symptoms because of its circulatory stimulant and anti-inflammatory effects. Anyway, up to now there is not any methodical literature review for evaluating the Z. zerumbet clinical effectiveness productiveness in treatment of OA. The main aim of the current study is to review scientific resources around therapeutic effectiveness of Zingiber zerumbet in treatment of adverse symptoms of OA disorder.
ABSTRACT
BACKGROUND: Chronic ocular complications of Sulfur Mustard (SM) exposure leads to severe ocular morbidity during time. The aim of this study was to compare serum levels of Interleukin 17 (IL-17), IL-12, vascular endothelial growth factor (VEGF)-C, VEGF-D and nitric oxide (NO) in SM-exposed patients versus the control group and to measure tear concentration of VEGF-C only in the SM-exposed group. METHODS: In this prospective case control, 128 SM-exposed patients and 31 healthy control subjects were included. In the case group ocular manifestations were classified to three subgroups of mild (19 cases), moderate (31 cases) and severe (78 cases) forms of disease. Serum levels of IL-17, IL-12, NO, VEGF-C and VEGF-D, in all subjects and tear concentration of VEGF-C in SM-exposed group was evaluated. RESULTS: All subjects were male and mean⯱â¯standard deviation (SD) of age in the case and control groups were 44.9⯱â¯8.8 and 40.9⯱â¯10.1â¯years, respectively. Except for significantly lower serum level of IL-17 (pâ¯<â¯0.001) and NO (pâ¯=â¯0.003), other values were not significantly different. The tear concentration of VEGF-C and serum level of IL-12 were not different between subgroups in the SM-exposed group, yet were significantly lower among those with abnormally dilated and tortuous conjunctival vessels and corneal pannus, respectively (pâ¯=â¯0.01, pâ¯=â¯0.015). CONCLUSIONS: Exposure to SM significantly reduced serum level of IL-17 and NO in the delayed phase, yet did not influence VEGF-C; VEGF-D or IL-12.