Development of nano-liposomal human growth hormone as a topical formulation for preventing uvb-induced skin damage.

Due to its involvement in skin maintenance and repair, topical administration of recombinant human growth hormone (rhGH) is an interesting strategy for therapeutic purposes. We have formulated and characterized a topical rhGH-loaded liposomal formulation (rhGH-Lip) and evaluated its safety, biological activity, and preventive role against UVB-induced skin damage. The rhGH-Lip had an average size and zeta potential of 63 nm and -33 mV, respectively, with 70 % encapsulation efficiency. The formulation was stable at 4 °C for at least one year. The SDS-PAGE and circular dichroism results showed no structural alterations in rhGH upon encapsulation. In vitro, studies in HaCaT, HFFF-2, and Ba/F3-rhGHR cell lines confirmed the safety and biological activity of rhGH-Lip. Franz diffusion cell study showed increased rhGH skin permeation compared to free rhGH. Animal studies in nude mice showed that liposomal rhGH prevented UVB-induced epidermal hyperplasia, angiogenesis, wrinkle formation, and collagen loss, as well as improving skin moisture. The results of this study show that rhGH-Lip is a stable, safe, and effective skin delivery system and has potential as an anti-wrinkle formulation for topical application. This study also provides a new method for the topical delivery of proteins and merits further investigation.

Measuring Equity of Geographical Distribution of Specialist Physicians in Iran's Health System.

Background: Equitable distribution of health care sector resources is one of the most important goals of health systems in all countries. The purpose of this study is to measure equity of geographical distribution of active specialist physicians in Iran's health system. Methods: The present study was a descriptive-cross-sectional. The statistical population included: all active specialist physicians working in the public, private, social insurance organization, military, charity, and the other health service providers in Iran in 2019. Studied demographic data were collected from Iran's national statistic center. Also, information of specialist physicians was obtained from several databases. Finally, duplicated records were removed, and the number of specialist physicians extracted. Data analysis was performed using Stata V.16 and ArcGIS 10.4 software. Results: The results showed that the number of specialist physicians per 100,000 population who worked in Iran's health system was 46.81. The provinces of Tehran had the highest and Sistan and Baluchestan had the lowest number of specialist physicians. Also, 52.63% of active specialist physicians provide health services in four provinces, whereas these provinces are 37.13% of the country's population. Total Gini coefficient of the distribution of active physicians in Iran in 2019 was 0.23. Conclusions: Distribution of specialist physician was different but somewhat equitable in the provinces. However, in some provinces, the ratio of specialist physicians to the population was still low. Therefore, when the number of specialist physicians increased, their distribution should be considered concurrently.

Modulation of Mesenchymal Stem Cells-Mediated Adaptive Immune Effectors' Repertoire in the Recovery of Systemic Lupus Erythematosus.

The breakdown of self-tolerance of the immune response can lead to autoimmune conditions in which chronic inflammation induces tissue damage. Systemic lupus erythematosus (SLE) is a debilitating multisystemic autoimmune disorder with a high prevalence in women of childbearing age; however, SLE incidence, prevalence, and severity are strongly influenced by ethnicity. Although the mystery of autoimmune diseases remains unsolved, disturbance in the proportion and function of B cell subsets has a major role in SLE's pathogenesis. Additionally, colocalizing hyperactive T helper cell subgroups within inflammatory niches are indispensable. Despite significant advances in standard treatments, nonspecific immunosuppression, the risk of serious infections, and resistance to conventional therapies in some cases have raised the urgent need for new treatment strategies. Without the need to suppress the immune system, mesenchymal stem cells (MSCs), as ''smart" immune modulators, are able to control cellular and humoral auto-aggression responses by participating in precursor cell development. In lupus, due to autologous MSCs disorder, the ability of allogenic engrafted MSCs in tissue regeneration and resetting immune homeostasis with the provision of a new immunocyte repertoire has been considered simultaneously. In Brief The bone marrow mesenchymal stem cells (BM-MSCs) lineage plays a critical role in maintaining the hematopoietic stem-cell microstructure and modulating immunocytes. The impairment of BM-MSCs and their niche partially contribute to the pathogenesis of SLE-like diseases. Allogenic MSC transplantation can reconstruct BM microstructure, possibly contributing to the recovery of immunocyte phenotype restoration of immune homeostasis. In terms of future prospects of MSCs, artificially gained by ex vivo isolation and culture adaptation, the wide variety of potential mediators and mechanisms might be linked to the promotion of the immunomodulatory function of MSCs.

Alpha-Lipoic Acid Can Overcome The Reduced Developmental Competency Induced by Alcohol Toxicity during Ovine Oocyte Maturation.

OBJECTIVE: Alpha-lipoic acid (ALA) as a strong antioxidant has a protective effect. This study was designed to assess whether supplementation of maturation medium with ALA during in vitro maturation (IVM) can attenuate the toxic effect of ethanol. MATERIALS AND METHODS: In this experimental study, to assess the antioxidant capacity of ALA challenged by 1% ethanol during in vitro maturation, immature ovine oocytes were exposed to 1% alcohol in the presence or absence of 25 µM ALA during oocyte maturation. The cumulus expansion index, intracellular reactive oxygen species (ROS), and thiol content levels were assessed in matured oocytes of various treatment groups. Consequently, the blastocyst formation rate of matured oocytes in various treatment groups were assessed. In addition, total cell number (TCN), cell allocation, DNA fragmentation, and relative gene expression of interested genes were assessed in resultant blastocysts. RESULTS: The results revealed that alcohol significantly reduced cumulus cells (CCs) expansion index and blastocyst yield and rate of apoptosis in resultant embryos. Addition of 25 µM ALA to 1% ethanol during oocyte maturation decreased ROS level and elevated Thiolcontent. Furthermore, supplementation of maturation medium with ALA attenuated the effect of 1% ethanol and significantly increased the blastocyst formation and hatching rate as compared to control and ethanol groups. In addition, the quality of blastocysts produced in ALA+ethanol was improved based on the low number of TUNEL positive cells, the increased expression level of mRNA for pluripotency, and anti-oxidant markers, and decreased expression of apoptotic genes. CONCLUSION: The current findings demonstrate that ALA can diminish the effect of ethanol, possibly by decreasing the ROS level and increasing Thiolcontent during oocyte maturation. Using the ALA supplement may have implications in protecting oocytes from alcohol toxicity in affected patients.

A retrospective cohort of coronary artery disease development after at least two angiograms in patients with normal coronary angiograms or mild coronary artery disease.

BACKGROUND: Coronary Artery Disease is one of the leading causes of death in the world. CAD usually progresses slowly during time and patients with normal or near-normal coronary arteries are also at risk of developing CAD. It is now believed that even mild atherosclerosis can increase the rate of CAD. METHODS: This is a retrospective, descriptive and analytic study. We selected patients who had undergone at least two diagnostic coronary angiographies at Tehran Heart Center and had normal coronary structure or mild CAD in initial angiography. The data was obtained from the Tehran Heart Center Angiography Databank. Predicting factors in the development of CAD were determined. RESULTS: Data on 556 patients were reviewed. The median interval between the initial and final coronary catheterization was 37.6 months. On the final evaluation, 216 patients (38.8%) found to have developed some degrees of coronary artery disease. Based on the multivariate analysis, age, hematocrit, cigarette smoking, hypertension, and initial presentation with stable and unstable angina were found to be independent predictors of progression to CAD in patients. CONCLUSION: In the end, 40% of patients who had normal coronary arteries or minimal CAD in the initial angiography report, developed some degrees of CAD and some clinical indices can predict the risk of CAD.

Harnessing the Power of Smart and Connected Health to Tackle COVID-19: IoT, AI, Robotics, and Blockchain for a Better World.

As COVID-19 hounds the world, the common cause of finding a swift solution to manage the pandemic has brought together researchers, institutions, governments, and society at large. The Internet of Things (IoT), artificial intelligence (AI)-including machine learning (ML) and Big Data analytics-as well as Robotics and Blockchain, are the four decisive areas of technological innovation that have been ingenuity harnessed to fight this pandemic and future ones. While these highly interrelated smart and connected health technologies cannot resolve the pandemic overnight and may not be the only answer to the crisis, they can provide greater insight into the disease and support frontline efforts to prevent and control the pandemic. This article provides a blend of discussions on the contribution of these digital technologies, propose several complementary and multidisciplinary techniques to combat COVID-19, offer opportunities for more holistic studies, and accelerate knowledge acquisition and scientific discoveries in pandemic research. First, four areas, where IoT can contribute are discussed, namely: 1) tracking and tracing; 2) remote patient monitoring (RPM) by wearable IoT (WIoT); 3) personal digital twins (PDTs); and 4) real-life use case: ICT/IoT solution in South Korea. Second, the role and novel applications of AI are explained, namely: 1) diagnosis and prognosis; 2) risk prediction; 3) vaccine and drug development; 4) research data set; 5) early warnings and alerts; 6) social control and fake news detection; and 7) communication and chatbot. Third, the main uses of robotics and drone technology are analyzed, including: 1) crowd surveillance; 2) public announcements; 3) screening and diagnosis; and 4) essential supply delivery. Finally, we discuss how distributed ledger technologies (DLTs), of which blockchain is a common example, can be combined with other technologies for tackling COVID-19.

Preparation and characterization of antibacterial magnetic-/pH-sensitive alginate/Ag/Fe3O4 hydrogel beads for controlled drug release.

This work reports the synthesis of novel antibacterial magnetic-/pH-sensitive hydrogel beads based on ionotropic-gelation of alginate biopolymer. Using pomegranate peels extract, green-Ag nanoparticles were synthesized inside a mixture of alginate and Fe3O4, via in situ method. The alginate beads were investigated by VSM, TEM, XRD, and FE-SEM techniques. The introducing Ag and Fe3O4 nanoparticles in hydrogel beads caused a reduction in the swelling capacity of hydrogel beads. Besides, a pH-dependent swelling behavior was observed for hydrogel beads with a maximum swelling capacity at pH = 7.4. Diclofenac sodium (DS) as a model drug was loaded in hydrogel beads and its release showed a pH-dependent behavior. Drug release studies exhibited significant behaviors on the subject of physiological simulated pHs with a high release rate at pH = 7.4. The alginate beads have shown a prolonged and successive controlled drug release nearly 83% at pH = 7.4 and time 200 min. In addition to the pH, the release of DS from magnetic beads was affected by the external-magnetic-fields. Also, the Ag-incorporated alginate beads showed strong antibacterial activity against S. aureus and E. coli. These results indicated that the hydrogel beads have potentially applicable in drug delivery systems.

Induced DNA hypomethylation by Folic Acid Deprivation in Bovine Fibroblast Donor Cells Improves Reprogramming of Somatic Cell Nuclear Transfer Embryos.

Aberrant patterns of DNA methylation are consistent events in SCNT derived embryos and mechanistically are believed to be related to abnormal development. While some epigenetic drugs have been used in attempts to improve SCNT efficiency but some concerns remained toward the safety of these drugs on the health of future offspring. Folate is an essential cofactor in one-carbon cycle for conversion of homocysteine to methionine, thereby ensuring supply of SAM, the universal methyl donor for many biological methylation reactions including DNA methylation. Therefore, in vitro DNA hypo-methylation can be induced by folate deprivation and this study aims at deciphering the role of folic acid deprivation in culture medium of BFFs for 6 days on SCNT efficiency. Our data revealed that culture of fibroblast cells in folate- medium containing 0.5% FBS did not alter the cell cycle compared to other groups. Flowcytometric analysis revealed that DNA methylation (5-mC level) in folate deprived cells cultured in 0.5% serum was decreased compared to folate+ group. The result of bisulfite sequencing was in accordance with flowcytometric analysis, which indicated a decrease in DNA methylation of POU5F1 promoter. Gene expression analysis revealed an increase in expression of POU5F1 gene in folate- group. The nuclear area of the cells in folate- group was significantly larger than folate+ group. Induced DNA hypomethylation by folate deprivation in the folate- group significantly improved blastocyst rate compared to the folate+ group. DNA methylation level in POU5F1 promoter and ICR of H19 and IGF2 of SCNT derived embryos in the folate- group was similar to the IVF derived blastocysts. In conclusion, our results proposes a promising "non-chemical" instead of "chemical" approach using inhibitors of epigenetic modifier enzymes for improving mammalian SCNT efficiency for agricultural and biomedical purposes.

Aerobic oxidative synthesis of quinazolinones and benzothiazoles in the presence of laccase/DDQ as a bioinspired cooperative catalytic system under mild conditions.

The current study applied laccase/DDQ as a bioinspired cooperative catalytic system for the synthesis of quinazolinones (80-95% yield) and benzothiazoles (65-98% yield) using air or O2 as ideal oxidants in aqueous media at ambient temperature. The aerobic oxidative cyclization reactions occur in two steps: (i) chemical cyclization; (ii) chemoenzymatic oxidation. These methods are more environment-friendly, efficient, simple and practical than other reported methods due to the use of O2 as an oxidant, laccase as an eco-friendly biocatalyst, aqueous media as the solvent and free from any toxic transition metal and halide catalysts. Therefore, these methods can be applied in pharmaceutical and other sensitive synthetic procedures.

Trends of geographic distribution of general practitioners in the public health sector of Iran.

BACKGROUND: Proper distribution of general practitioners (GPs) is one of the challenges in all health systems. This study aimed to investigate geographical distribution of GPs in public health sector in Iran between 2010 and 2016. METHODS: The study is a descriptive-cross-sectional study. The population of provinces was extracted from Iran's National Statistic Center, while information on GPs was gathered from deputy of statistic and information technology in Ministry of Health and Medical Education. Data analysis was carried out using descriptive statistics, Gini coefficient (GC), and by drawing geographical distribution map of GPs. Data analysis was performed by excel 2013, Stata V.14, and Arc GIS software. RESULTS: The results of calculating the number of GPs per 100,000 population in Iran showed that, in year 2010, Chaharmahal and Bakhtiari Province had the highest (10.39) and Alborz Province had the lowest (0.66) number of per capita GPs. The highest number of GPs per 100,000 population among Iran's provinces belonged to Chaharmahal and Bakhtiari (8.97), while the lowest belonged to Tehran (0.28) in year 2016. The GC was 0.31 in year 2010 and 0.283 for 2011. The lowest GC belonged to year 2012 (GC = 0.272), while the largest coefficient belonged to year 2016 (0.356). CONCLUSIONS: According to the results of this study, the distribution of GPs in public health sector of Iran in between 2010 and 2016 showed inequality. Therefore, along with increasing the number of GPs working in public health sector, it is necessary to pay attention to their distribution. Further studies are needed to investigate inequality of GPs within and between the provinces.

Opportunities and challenges of resident specialists' attendance plan guidelines (health-care transformation plan) in Isfahan university hospitals in 2015.

BACKGROUND: Given new reforms in Iran's health-care system and due to the need for gathering evidence regarding the implementation of this plan, this study aimed to investigate opportunities and challenges created by resident specialist attendance plan guidelines in university hospitals. MATERIALS AND METHODS: This study used the qualitative method. Semi-structured interviews were used for data gathering. The study population included all experts of Isfahan University of Medical Science. Sampling was carried out using purposeful sampling method and continued until data saturation was reached. In total, 16 experts were interviewed. Criteria such as "reliability of information," "trustworthiness," and "verifiability of the information" were considered. Interviewees were assured that their names would keep hidden and that all information is confidential. Subject analysis method was used for data analysis. RESULTS: The findings of this study based on subject analysis led to extracting three themes in regards of challenges in the implementation of resident (specialist or fellowship) plan in hospitals including structural, management, and resource challenges and one theme in the area of opportunities which were improved quality and timely provision of services. CONCLUSION: The findings showed that despite the strengths of this guideline, there are some fundamental challenges in various areas and need better attention by national level policymakers. These results help health-care policymakers to evaluate the problem with a better attitude and improve the necessary plans for implementation of these guidelines.

DFT study on the chemical sensing properties of B24N24 nanocage toward formaldehyde.

It has been previously shown that the toxic formaldehyde gas (H2CO) cannot be detected by pristine BC2N, carbon, and BN nanotubes, BC3 nanosheet and graphene. Herein, density functional theory calculations were employed to investigate the electronic and structural behavior of a pristine B24N24 nanocluster toward H2CO molecules. It was found that [4,6] BN bonds of the nanocluster are the most favorable sites for the H2CO adsorption, compared to the [4,8], and [6,8] ones. When an H2CO molecule is adsorbed on a [4,6] BN bond, an energy of about 16.40kcal/mol is released and the HOMO-LUMO gap of the cluster is decreased from 6.45 to 2.98eV. Thus, the electrical conductivity of the cluster is significantly increased, indicating that it can produce an electronic noise at the presence of H2CO molecules. Increasing the number of adsorbed H2CO molecules, the electrical conductivity more increases. The recovery time for the H2CO from the surface of B24N24 is calculated to be very short (∼1.02s). Also, the UV-vis spectrum shows that the λmax of the B24N24 shows a large redshift upon the adsorption process and transfers from the UV to the visible region.

Death Portrait of Isfahan Province in Years 2007-2011.

BACKGROUND: The rapid rise in noncommunicable diseases (NCDs) is one of the main health challenges affecting the global development in the present era. This raising challenge is a major threat to countries' socioeconomic development as well as millions of people health. METHODS: It was a retrospective study with analysis of reported death in Isfahan Province during a 5-year period from 2007 to 2011. Required data were collected from statistics provided by Deputy of Health in Kashan and Isfahan Universities of Medical Sciences in 2012. Excel software was used for data analysis. RESULTS: During this period, the cardiovascular events, cancers and tumors, unintentional injuries, respiratory diseases, and prenatal mortality were the main reasons of mortality in Isfahan Province. The overall rate of cardiovascular events rose 5.10% in the 5-years of the study observation, and Khor - Biabanak was on the top of the list; while in cancer rating Khor - Biabanak, Golpayegan, and Khansar both stood at the outset (per 1,000 people). For injuries, the highest rate belonged to Golpayegan, Tiran-Kervan, and Chadegan. Meanwhile, for mental illnesses, the highest rate was observed in Khomeini Shahr. Moreover, the highest maternal and fetal mortality was reported in Fereydunshahr, Khor - Biabanak and Mobarakeh. CONCLUSIONS: Given the sharp rise of NCD, programs by health care system should be directed toward lifestyle modification while a proper framework should be determined to deal with these kinds of disease. Furthermore, optimal allocation of resources based on needs can provide better facilities for different cities.

Simultaneous determination of 6-mercaptopruine, 6-thioguanine and dasatinib as three important anticancer drugs using nanostructure voltammetric sensor employing Pt/MWCNTs and 1-butyl-3-methylimidazolium hexafluoro phosphate.

6-Mercaptopurine, 6-thioguanine and dasatinib are three important anticancer drugs with high adverse effects in human body. In this study, a Pt/MWCNTs-1-butyl-3-methylimidazolium hexafluoro phosphate-modified carbon paste electrode was developed for the simultaneously determination of 6-mercaptopurine, 6-thioguanine and dasatinib for the first time. The Pt/MWCNTs synthesized by polyol method and have been characterized by transmission electron microscopy and X-ray diffraction methods. The obtained data revealed that the electro-oxidation of 6-mercaptopurine, 6-thioguanine and dasatinib is facilitated as a novel voltammetric sensor. After optimization of electrochemical parameters employing this sensor at pH 8.0, the oxidation peak currents for 6-mercaptopurine, 6-thioguanine and dasatinib were found to vary linearly with their concentrations in the range of 0.05-550µM; 0.1-500µM and 5.0-500µM with detection limits of 0.009µM, 0.05µM and 1.0µM respectively using square wave voltammetric method. The modified electrode has been applied for the selective and precise analysis of 6-mercaptopurine, 6-thioguanine and dasatinib in pharmaceutical formulations and urine samples.

A high sensitive biosensor based on FePt/CNTs nanocomposite/N-(4-hydroxyphenyl)-3,5-dinitrobenzamide modified carbon paste electrode for simultaneous determination of glutathione and piroxicam.

This study describes the development, electrochemical characterization and utilization of novel modified N-(4-hydroxyphenyl)-3,5-dinitrobenzamide-FePt/CNTs carbon paste electrode for the electrocatalytic determination of glutathione (GSH) in the presence of piroxicam (PXM) for the first time. The synthesized nanocomposite was characterized with different methods such as TEM and XRD. The modified electrode exhibited a potent and persistent electron mediating behavior followed by well-separated oxidation peaks of GSH and PXM. The peak currents were linearly dependent on GSH and PXM concentrations in the range of 0.004-340 and 0.5-550 µmol L(-1), with detection limits of 1.0 nmol L(-1) and 0.1 µmolL(-1), respectively. The modified electrode was successfully used for the determination of the analytes in real samples with satisfactory results.