Multiprotein collagen/keratin hydrogel promoted myogenesis and angiogenesis of injured skeletal muscles in a mouse model.

Volumetric loss is one of the challenging issues in muscle tissue structure that causes functio laesa. Tissue engineering of muscle tissue using suitable hydrogels is an alternative to restoring the physiological properties of the injured area. Here, myogenic properties of type I collagen (0.5%) and keratin (0.5%) were investigated in a mouse model of biceps femoris injury. Using FTIR, gelation time, and rheological analysis, the physicochemical properties of the collagen (Col)/Keratin scaffold were analyzed. Mouse C2C12 myoblast-laden Col/Keratin hydrogels were injected into the injury site and histological examination plus western blotting were performed to measure myogenic potential after 15 days. FTIR indicated an appropriate interaction between keratin and collagen. The blend of Col/Keratin delayed gelation time when compared to the collagen alone group. Rheological analysis revealed decreased stiffening in blended Col/Keratin hydrogel which is favorable for the extrudability of the hydrogel. Transplantation of C2C12 myoblast-laden Col/Keratin hydrogel to injured muscle tissues led to the formation of newly generated myofibers compared to cell-free hydrogel and collagen groups (p < 0.05). In the C2C12 myoblast-laden Col/Keratin group, a low number of CD31+ cells with minimum inflammatory cells was evident. Western blotting indicated the promotion of MyoD in mice that received cell-laden Col/Keratin hydrogel compared to the other groups (p < 0.05). Despite the increase of the myosin cell-laden Col/Keratin hydrogel group, no significant differences were obtained related to other groups (p > 0.05). The blend of Col/Keratin loaded with myoblasts provides a suitable myogenic platform for the alleviation of injured muscle tissue.

Polyurethane-based nanofibrous mat containing porphyrin with photosensitivity and bactericidal properties can promote cutaneous tissue healing in rats.

The regeneration of cutaneous tissue is one of the most challenging issues in human regenerative medicine. To date, several studies have been done to promote cutaneous tissue healing with minimum side effects. The healing potential of polyurethane (PU)/Poly (caprolactone)-poly (ethylene glycol)-poly (caprolactone) (PCEC)/chitosan (CS) (PCS) nanofibrous mat with cationic photosensitizer meso tetrakis (N-methyl pyridinium-4-yl) porphyrin tetratosylate salt (TMP) was examined. The CS tripolyphosphate nanoparticles (CSNPs) were prepared and loaded by TMP to provide an efficient drug release system (TMPNPs) for delivery of TMP to promote wound healing. In in vitro setting, parameters such as bactericidal effects, cytocompatibility, and hemolytic effects were examined. The healing potential of prepared nanofibrous mats was investigated in a rat model of full-thickness cutaneous injury. PCS/TMP/TMPNPs nanofibers can efficiently release porphyrin in the aqueous phase. The addition of TMPNPs and CS to the PU backbone increased the hydrophilicity, degradation, and reduced mechanical properties. The culture of human fetal foreskin fibroblasts (HFFF2) on PCS/TMP/TMPNPs scaffold led to an increased survival rate and morphological adaptation analyzed by MTT and SEM images. Irradiation with a red laser (635 nm, 3 J/cm2) for the 30 s reduced viability of S. aureus and E. Coli bacteria plated on PCS/TMP and PCS/TMP/TMPNPs nanofibrous mats compared to PU/PCEC (PC) and PU/PCEC/CS (PCS) groups, indicating prominent antibacterial effects of PCS/TMP and PCS/TMP/TMPNPs nanofibrous (p < 0.05). Data indicated that PCS/TMP/TMPNPs mat enhanced healing of the full-thickness excisional wound in a rat model by the reduction of inflammatory response and fibrotic changes compared to the PC, and PCS groups (p < 0.05). Immunofluorescence imaging indicated that levels of Desmoglein were increased in rats that received PCS/TMP/TMPNPs compared to the other groups. It is found that a PU-based nanofibrous mat is an appropriate scaffold to accelerate the healing of injured skin.

Putative therapeutic impacts of cardiac CTRP9 in ischaemia/reperfusion injury.

Recently, cytokines belonging to C1q/tumour necrosis factor-related proteins (CTRPs) superfamily have attracted increasing attention due to multiple metabolic functions and desirable anti-inflammatory effects. These various molecular effectors exhibit key roles upon the onset of cardiovascular diseases, making them novel adipo/cardiokines. This review article aimed to highlight recent findings correlated with therapeutic effects and additional mechanisms specific to the CTRP9, particularly in cardiac ischaemia/reperfusion injury (IRI). Besides, the network of the CTPR9 signalling pathway and its possible relationship with IRI were discussed. Together, the discovery of all involved underlying mechanisms could shed light to alleviate the pathological sequelae after the occurrence of IRI.

Interaction of alginate with nano-hydroxyapatite-collagen using strontium provides suitable osteogenic platform.

BACKGROUND: Hydrogels based on organic/inorganic composites have been at the center of attention for the fabrication of engineered bone constructs. The establishment of a straightforward 3D microenvironment is critical to maintaining cell-to-cell interaction and cellular function, leading to appropriate regeneration. Ionic cross-linkers, Ca2+, Ba2+, and Sr2+, were used for the fabrication of Alginate-Nanohydroxyapatite-Collagen (Alg-nHA-Col) microspheres, and osteogenic properties of human osteoblasts were examined in in vitro and in vivo conditions after 21 days. RESULTS: Physicochemical properties of hydrogels illustrated that microspheres cross-linked with Sr2+ had reduced swelling, enhanced stability, and mechanical strength, as compared to the other groups. Human MG-63 osteoblasts inside Sr2+ cross-linked microspheres exhibited enhanced viability and osteogenic capacity indicated by mineralization and the increase of relevant proteins related to bone formation. PCR (Polymerase Chain Reaction) array analysis of the Wnt (Wingless-related integration site) signaling pathway revealed that Sr2+ cross-linked microspheres appropriately induced various signaling transduction pathways in human osteoblasts leading to osteogenic activity and dynamic growth. Transplantation of Sr2+ cross-linked microspheres with rat osteoblasts into cranium with critical size defect in the rat model accelerated bone formation analyzed with micro-CT and histological examination. CONCLUSION: Sr2+ cross-linked Alg-nHA-Col hydrogel can promote functionality and dynamic growth of osteoblasts.

Culture of rabbit bone marrow mesenchymal stem cells on polyurethane/pyrrole surface promoted differentiation into endothelial lineage.

Due to the electrical conductivity, pyrrole-based scaffolds are one of the attractive biomaterials in the regeneration of electrically active tissues like the heart and brain. Here, we investigated the impact of polyurethane/pyrrole scaffold on the angiogenesis differentiation of rabbit mesenchymal stem cells toward endothelial lineage in vitro. Nanoelectrospun polyurethane/pyrrole fibers were synthesized and characterized using attenuated total reflection-Fourier transform infrared (ATR-FTIR) spectrum analysis, scanning electron microscope (SEM) imaging. Mechanical properties, electroconductivity, and hydrophobicity were also measured. The viability of cells was monitored 72 hours after being plated on the polyurethane/pyrrole surface. The endothelial differentiation of stem cells was explored using western blotting. ATR-FTIR revealed that the pyrrole was successfully polymerized to polypyrrole and blend with polyurethane fibers. The addition of pyrrole to polyurethane increased the tensile strength compared to the polyurethane group. These features coincided with the reduction of the hydrophilic properties of polyurethane. Based on our data, the electro-conductivity of polyurethane/pyrrole was superior compared to the polyurethane group. SEM imaging showed an appropriate cell attachment to the surface of polyurethane/pyrrole and polyurethane groups synthesized membranes. MTT assay revealed a significantly increased survival rate in the polyurethane/pyrrole group compared to the polyurethane group (P < .05). We noted a statistically significant increase of endothelial-associated proteins, CD31, von Willebrand factor, and CD34, in cells expanded on polyurethane/pyrrole compared to the polyurethane group (P < .05). As a more general note, it could be hypothesized that the polyurethane/pyrrole blend could improve the angiogenesis potency of rabbit bone marrow mesenchymal stem cells for regenerative purposes.

Comparison of end-to-side hand-sewn and side-to-side stapled cervical esophagogastric anastomosis in patients with lower thoracic esophageal cancer undergoing transhiatal esophagectomy: an Iranian retrospective cohort study.

BACKGROUND: Controversies in terms of efficacy and postoperative advantages surround stapled esophagogastric anastomosis compared with the hand-sewn technique as a treatment for patients with esophageal cancer. The purpose of this study was to compare the clinical outcomes of hand-sewn end-to-side esophago-gastrostomy and side-to-side stapled cervical esophagogastric anastomosis after esophagectomy for the aforementioned patients. METHODS: This retrospective cohort study involved examining the medical records of 433 patients who underwent transhiatal esophagectomy for esophageal cancer from March 2010 to March 2016. All the patients were operated using end-to-side hand-sewn esophago-gastrostomy and side-to-side stapled cervical esophagogastric anastomosis. 409 of the patients received a year's worth of follow-up evaluations. All the cases were revisited in 2 weeks as well as in four, eight, and 12 months after surgery. The patients were assessed in terms of postoperative outcomes, including reflux symptoms, anastomotic leakage and stricture, and the need for anastomotic dilatation. RESULTS: Hand-sewn anastomosis was carried out in 271 (62.5%) patients, whereas stapled anastomosis was performed in 162 (37.4%) patients. The mean operative times were 214.46 ± 84.33 min and 250.55 ± 43.31 min for the stapled and hand-sewn anastomosis groups, respectively (P = 0.028). The two groups showed no significant differences with respect to stays in intensive care units and hospitals. Postoperatively, 38 (14.67%) cases of anastomotic leakage were detected in the hand-sewn anastomosis group, with incidence being significantly higher than that in the stapled anastomosis group (8 cases or 5.33%; P = 0.002). Anastomotic stricture occurred less frequently in the patients who underwent stapled anastomosis (P = 0.004). Within the one-year follow-up period, the patients treated via hand-sewn anastomosis more frequently required anastomotic dilatation (P = 0.02). CONCLUSION: Side-to-side stapled cervical esophagogastric anastomosis may reduce operation times and decrease the rates of anastomotic leakage, anastomotic stricture, and anastomotic dilatation in patients with lower thoracic esophageal cancer undergoing transhiatal esophagectomy.

Toll-like receptors in the functional orientation of cardiac progenitor cells.

Cardiac progenitor cells (CPCs) have the potential to differentiate into several cell lineages with the ability to restore in cardiac tissue. Multipotency and self-renewal activity are the crucial characteristics of CPCs. Also, CPCs have promising therapeutic roles in cardiac diseases such as valvular disease, thrombosis, atherosclerosis, congestive heart failure, and cardiac remodeling. Toll-like receptors (TLRs), as the main part of the innate immunity, have a key role in the development and differentiation of immune cells. Some reports are found regarding the effect of TLRs in the maturation of stem cells. This article tried to find the potential role of TLRs in the dynamics of CPCs. By showing possible crosstalk between the TLR signaling pathways and CPCs dynamics, we could achieve a better conception related to TLRs in the regeneration of cardiac tissue.

Cardioprotective role of extracellular vesicles: A highlight on exosome beneficial effects in cardiovascular diseases.

Extracellular vesicles (EVs) are nano-sized vesicles, released from many cell types including cardiac cells, have recently emerged as intercellular communication tools in cell dynamics. EVs are an important mediator of signaling within cells that influencing the functional behavior of the target cells. In heart complex, cardiac cells can easily use EVs to transport bioactive molecules such as proteins, lipids, and RNAs to the regulation of neighboring cell function. Cross-talk between intracardiac cells plays pivotal roles in the heart homeostasis and in adaptive responses of the heart to stress. EVs were released by cardiomyocytes under baseline conditions, but stress condition such as hypoxia intensifies secretome capacity. EVs secreted by cardiac progenitor cells and cardiosphere-derived cells could be pinpointed as important mediators of cardioprotection and cardiogenesis. Furthermore, EVs from many different types of stem cells could potentially exert a therapeutic effect on the damaged heart. Recent evidence shows that cardiac-derived EVs are rich in microRNAs, suggesting a key role in the controlling of cellular processes. EVs harboring exosomes may be clinically useful in cell-free therapy approaches and potentially act as prognosis and diagnosis biomarkers of cardiovascular diseases.

Curcumin ameliorated myocardial infarction by inhibition of cardiotoxicity in the rat model.

Cardiovascular diseases are the main cause of death globally. Many attempts have been done to ameliorate the pathological changes after the occurrence of myocardial infarction. Curcumin is touted as a polyphenol phytocompound with appropriate cardioprotective properties. In this study, the therapeutic effect of curcumin was investigated on acute myocardial infarction in the model of rats. Rats were classified into four groups; control, isoproterenol hydrochloride (ISO) (100 mg/kbw), curcumin (50 mg/kbw), and curcumin plus ISO treatment groups. After 9-day administration of curcumin, levels of lactate dehydrogenase (LDH), creatine kinase (CK), and cardiac troponin I (cTnI) were determined. Superoxide dismutase (SOD) and malondialdehyde (MDA) contents were measured to investigate the oxidative status in infarct rats received curcumin. By using H & E staining, tissue inflammation was performed. Masson's trichrome staining was conducted to show cardiac remodeling and collagen deposition. The number of apoptotic cells was determined by using the terminal deoxynucleotidyl transferase dUTP nick end labeling assay. Data showed the serum decrease of LDH, CK, and cTnI in infarct rats after curcumin intake compared to the rats given (ISO) ( P < 0.05). Curcumin was found to reduce oxidative status by reducing SOD and MDA contents ( P < 0.05). Gross and microscopic examinations revealed that the decrease of infarct area, inflammation response and collagen deposition in rats given ISO plus curcumin ( P < 0.05). We noted the superior effect of curcumin to reduce the number of apoptotic cardiomyocytes after 9 days. Data point the cardioprotective effect of curcumin to diminish the complication of infarction by the reduction of cell necrosis and apoptosis in a rat model of experimental infarction.

Spatial and temporal variability of fluoride concentrations in groundwater resources of Larestan and Gerash regions in Iran from 2003 to 2010.

There is discrepancy about intervals of fluoride monitoring in groundwater resources by Iranian authorities. Spatial and temporal variability of fluoride in groundwater resources of Larestan and Gerash regions in Iran were analyzed from 2003 to 2010 using a geospatial information system and the Mann-Kendall trend test. The mean concentrations of fluoride for the 8-year period in the eight cities and 31 villages were 1.6 and 2.0 mg/l, respectively; the maximum values were 2.4 and 3.8 mg/l, respectively. Spatial, temporal, and spatiotemporal variability of fluoride in overall groundwater resources were relatively constant over the years. However, results of the Mann-Kendall trend test revealed a monotonic trend in the time series of one city and 11 villages for the 8-year period. Specifically, one city and three villages showed positive significant Kendall's Tau values, suggesting an upward trend in fluoride concentrations over the 8-year period. In contrast, seven villages displayed negative significant Kendall's Tau values, arguing for a downward trend in fluoride concentrations over the years. From 2003 to 2010, approximately 52 % of the Larestan and Gerash areas have had fluoride concentrations above the maximum permissible Iranian drinking water standard fluoride level (1.4 mg/l), and about 116,000 people were exposed to such excess amounts. Therefore, our study supports for a close monitoring of fluoride concentrations from health authorities in monthly intervals, especially in villages and cities that showed positive trend in fluoride concentrations. Moreover, we recommend simultaneous implementation of cost-effective protective measures or interventions until a standard fluoride level is achieved.

Global, regional, and national levels and causes of maternal mortality during 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013.

BACKGROUND: The fifth Millennium Development Goal (MDG 5) established the goal of a 75% reduction in the maternal mortality ratio (MMR; number of maternal deaths per 100,000 livebirths) between 1990 and 2015. We aimed to measure levels and track trends in maternal mortality, the key causes contributing to maternal death, and timing of maternal death with respect to delivery. METHODS: We used robust statistical methods including the Cause of Death Ensemble model (CODEm) to analyse a database of data for 7065 site-years and estimate the number of maternal deaths from all causes in 188 countries between 1990 and 2013. We estimated the number of pregnancy-related deaths caused by HIV on the basis of a systematic review of the relative risk of dying during pregnancy for HIV-positive women compared with HIV-negative women. We also estimated the fraction of these deaths aggravated by pregnancy on the basis of a systematic review. To estimate the numbers of maternal deaths due to nine different causes, we identified 61 sources from a systematic review and 943 site-years of vital registration data. We also did a systematic review of reports about the timing of maternal death, identifying 142 sources to use in our analysis. We developed estimates for each country for 1990-2013 using Bayesian meta-regression. We estimated 95% uncertainty intervals (UIs) for all values. FINDINGS: 292,982 (95% UI 261,017-327,792) maternal deaths occurred in 2013, compared with 376,034 (343,483-407,574) in 1990. The global annual rate of change in the MMR was -0·3% (-1·1 to 0·6) from 1990 to 2003, and -2·7% (-3·9 to -1·5) from 2003 to 2013, with evidence of continued acceleration. MMRs reduced consistently in south, east, and southeast Asia between 1990 and 2013, but maternal deaths increased in much of sub-Saharan Africa during the 1990s. 2070 (1290-2866) maternal deaths were related to HIV in 2013, 0·4% (0·2-0·6) of the global total. MMR was highest in the oldest age groups in both 1990 and 2013. In 2013, most deaths occurred intrapartum or postpartum. Causes varied by region and between 1990 and 2013. We recorded substantial variation in the MMR by country in 2013, from 956·8 (685·1-1262·8) in South Sudan to 2·4 (1·6-3·6) in Iceland. INTERPRETATION: Global rates of change suggest that only 16 countries will achieve the MDG 5 target by 2015. Accelerated reductions since the Millennium Declaration in 2000 coincide with increased development assistance for maternal, newborn, and child health. Setting of targets and associated interventions for after 2015 will need careful consideration of regions that are making slow progress, such as west and central Africa. FUNDING: Bill & Melinda Gates Foundation.

Potential impact of air pollution on multiple sclerosis in Tehran, Iran.

BACKGROUND: Multiple sclerosis (MS) incidence has dramatically increased in Tehran, Iran. The health impact of air pollution in Tehran underscores the attention to a possible association to this environmental risk factor. In this study, the authors aimed to analyze the spatial distribution of prevalent MS cases and their association with the spatial patterns of air pollution. METHODS: Patient records meeting McDonald's criteria for definite MS diagnosis with disease onset during 2003-2013 were obtained. Next, the location of 2,188 patients was successfully geo-referenced within Tehran metropolis by geographic information system (GIS) bureau of Iran's post office based on their phone numbers. A cluster analysis was performed using the average nearest neighbor index (ANNI) and quadrat analysis. The long-term exposures of MS patients to particulate matter (PM10), sulfur dioxide (SO2), nitrogen oxide (NO), nitrogen dioxide (NO2), and nitrogen oxides (NOx) were estimated using the previously developed land use regression models. RESULTS: Prevalent MS cases had a clustered pattern in Tehran. A significant difference in exposure to PM10, SO2, NO2, and NOx (p < 0.001) was observed in MS cases compared with controls. CONCLUSION: This study revealed the potential role of long-term exposure to air pollutants as an environmental risk factor in MS.

How within-city socioeconomic disparities affect life expectancy? Results of Urban HEART in Tehran, Iran.

BACKGROUND: There is substantial lack of knowledge about the role of socioeconomic status (SES) indicators on life expectancy (LE) within-cities, especially within mega-cities. We aimed to investigate the disparities of LE within city districts of Tehran, Iran, and specify how SES inequalities play role on LE. METHODS: The death and population data for 2010 by different age, gender, and residency district were obtained from the main cemetery of Tehran and statistical centre of Iran, respectively. Age-specific mortality rates and consequently LE were calculated for all 22 districts by different genders. Finally, based on the results of first Tehran's Urban Health Equity Assessment and Response Tool (Urban HEART) project in 2008, the influence of social classes (SCs), total costs, and education indicators were analyzed on LE at birth (e0). RESULTS: The e0 for total males and females in Tehran were calculated as 74.6 and 78.4 years for 2010, respectively. The maximum LE of 80 years was observed in females of northern part with higher SES, and the minimum e0 of 72.7 years observed in males of southern part with lower SES. The e0 gender gap among districts was 5.5 years for females and 3.7 years for males. The highest and lowest mean of e0 observed in SC1 (highest class) and SC5 (lowest class), were 77.6 and 76.0 years, respectively. The lowest mean of e0 observed in the first group of total costs indicator and was 76.2 years. In addition, the lowest observed mean of e0 was in the first category of education indicator (illiterate) and was 76.0 years. CONCLUSION: RESULTS indicate substantial disparities in LE within city districts. This confirms that SES disparities within-cities would have direct influences on LE.

Tissue engineering modalities in skeletal muscles: focus on angiogenesis and immunomodulation properties.

Muscular diseases and injuries are challenging issues in human medicine, resulting in physical disability. The advent of tissue engineering approaches has paved the way for the restoration and regeneration of injured muscle tissues along with available conventional therapies. Despite recent advances in the fabrication, synthesis, and application of hydrogels in terms of muscle tissue, there is a long way to find appropriate hydrogel types in patients with congenital and/or acquired musculoskeletal injuries. Regarding specific muscular tissue microenvironments, the applied hydrogels should provide a suitable platform for the activation of endogenous reparative mechanisms and concurrently deliver transplanting cells and therapeutics into the injured sites. Here, we aimed to highlight recent advances in muscle tissue engineering with a focus on recent strategies related to the regulation of vascularization and immune system response at the site of injury.

Exosome-loaded microneedle patches: Promising factor delivery route.

During the past decades, the advent of different microneedle patch (MNPs) systems paves the way for the targeted and efficient delivery of several growth factors into the injured sites. MNPs consist of several micro-sized (25-1500 µm) needle rows for painless delivery of incorporated therapeutics and increase of regenerative outcomes. Recent data have indicated the multifunctional potential of varied MNP types for clinical applications. Advances in the application of materials and fabrication processes enable researchers and clinicians to apply several MNP types for different purposes such as inflammatory conditions, ischemic disease, metabolic disorders, vaccination, etc. Exosomes (Exos) are one of the most interesting biological bioshuttles that participate in cell-to-cell paracrine interaction with the transfer of signaling biomolecules. These nano-sized particles, ranging from 50 to 150 nm, can exploit several mechanisms to enter the target cells and deliver their cargo into the cytosol. In recent years, both intact and engineered Exos have been increasingly used to accelerate the healing process and restore the function of injured organs. Considering the numerous benefits provided by MNPs, it is logical to hypothesize that the development of MNPs loaded with Exos provides an efficient therapeutic platform for the alleviation of several pathologies. In this review article, the authors collected recent advances in the application of MNP-loaded Exos for therapeutic purposes.

Exosome-bearing hydrogels and cardiac tissue regeneration.

BACKGROUND: In recent years, cardiovascular disease in particular myocardial infarction (MI) has become the predominant cause of human disability and mortality in the clinical setting. The restricted capacity of adult cardiomyocytes to proliferate and restore the function of infarcted sites is a challenging issue after the occurrence of MI. The application of stem cells and byproducts such as exosomes (Exos) has paved the way for the alleviation of cardiac tissue injury along with conventional medications in clinics. However, the short lifespan and activation of alloreactive immune cells in response to Exos and stem cells are the main issues in patients with MI. Therefore, there is an urgent demand to develop therapeutic approaches with minimum invasion for the restoration of cardiac function. MAIN BODY: Here, we focused on recent data associated with the application of Exo-loaded hydrogels in ischemic cardiac tissue. Whether and how the advances in tissue engineering modalities have increased the efficiency of whole-based and byproducts (Exos) therapies under ischemic conditions. The integration of nanotechnology and nanobiology for designing novel smart biomaterials with therapeutic outcomes was highlighted. CONCLUSION: Hydrogels can provide suitable platforms for the transfer of Exos, small molecules, drugs, and other bioactive factors for direct injection into the damaged myocardium. Future studies should focus on the improvement of physicochemical properties of Exo-bearing hydrogel to translate for the standard treatment options.

Phenolated alginate hydrogel induced osteogenic properties of mesenchymal stem cells via Wnt signaling pathway.

Osteogenic properties of phenolated alginate (1.2 %) hydrogel containing collagen (0.5 %)/nano-hydroxyapatite (1 %) were studied on human mesenchymal stem cells in vitro. The phenolation rate and physical properties of the hydrogel were assessed using nuclear magnetic resonance (NMR), Fourier-transform infrared spectroscopy (FTIR), Scanning electron microscope (SEM), swelling ratio, gelation time, mechanical assay, and degradation rate. The viability of encapsulated cells was monitored on days 7, 14, and 21 using an MTT assay. Osteoblast differentiation was studied using western blotting, and real-time PCR. Using PCR array analysis, the role of the Wnt signaling pathway was also investigated. Data showed that the combination of alginate/collagen/nanohydroxyapatite yielded proper mechanical features. The addition of nanohydroxyapatite, and collagen reduced degradation, swelling rate coincided with increased stiffness. Elasticity and pore size were also diminished. NMR and FTIR revealed suitable incorporation of collagen and nanohydroxyapatite in the structure of alginate. Real-time PCR analysis and western blotting indicated the expression of osteoblast-related genes such as Runx2 and osteocalcin. PCR array revealed the induction of numerous genes related to Wnt signaling pathways during the maturation of human stem cells toward osteoblast-like cells. In vivo data indicated that transplantation of phenolated alginate/collagen/nanohydroxyapatite hydrogel led to enhanced de novo bone formation in rats with critical-sized calvarial defects. Phenolated alginate hydrogel can promote the osteogenic capacity of human amniotic membrane mesenchymal stem cells in the presence of nanohydroxyapatite and collagen via engaging the Wnt signaling pathway.

Asthma can Promote Cardiomyocyte Mitophagy in a Rat Model.

Clinical observations have shown the risk of cardiovascular disease during asthmatic changes. Whether and how asthma causes heart failure is the subject of debate. Here, we aimed to investigate the possibility of cardiomyocyte mitophagy in a rat model of asthma. Twelve mature Wistar rats were randomly allocated into the Control and Asthmatic rats (n = 6). To induce asthma, ovalbumin was injected intraperitoneally on days 1 and 8 and procedure followed by nebulization from days 14 to 32. After 2 weeks, we performed the pathological examination of both lungs and heart using Hematoxylin-Eosin staining. Real-time PCR analysis was used to measure the expression of mitophagic factors, such as Optineurin, Pink1, and mitofusin 1 and 2. Typical changes like increased inter-alveolar septa thickness and interstitial pneumonia were evident in asthmatic lungs. In cardiac tissue, slight inflammatory response, and hydropic degeneration with an eosinophilic appearance were detected in the cytoplasm of cardiomyocytes. Real-time PCR analysis showed mitophagic response in pulmonary and cardiac tissues via upregulation of mitophagy-related genes like Optineurin and Pink-1 in asthmatic lungs and hearts compared to the control group (p < 0.05). Likewise, asthmatic changes increased the expression of genes associated with mitochondrial fusion in the lungs and heart. The expression of mitofusin1 and 2 was significantly increased following inflammatory response in pulmonary and cardiac tissues (p < 0.05). Our findings showed the expression of certain factors related to mitophagy during chronic asthmatic conditions. The findings open a new avenue in the understanding of cardiomyocyte injury during asthma.

Application of microneedle patches for drug delivery; doorstep to novel therapies.

In the past decade, microneedle-based drug delivery systems showed promising approaches to become suitable and alternative for hypodermic injections and can control agent delivery without side effects compared to conventional approaches. Despite these advantages, the procedure of microfabrication is facing some difficulties. For instance, drug loading method, stability of drugs, and retention time are subjects of debate. Besides, the application of novel refining fabrication methods, types of materials, and instruments are other issues that need further attention. Herein, we tried to summarize recent achievements in controllable drug delivery systems (microneedle patches) in vitro and in vivo settings. In addition, we discussed the influence of delivered drugs on the cellular mechanism and immunization molecular signaling pathways through the intradermal delivery route. Understanding the putative efficiency of microneedle patches in human medicine can help us develop and design sophisticated therapeutic modalities.

Exposure assessment to dust and free silica for workers of Sangan iron ore mine in Khaf, Iran.

We aimed to conduct an exposure assessment to dust and free silica for workers of Sangan iron ore mine in Khaf, Iran. The maximum concentrations of total dust and free silica were measured in crusher machine station at 801 ± 155 and 26 ± 7 mg/m(3), respectively. Meanwhile, the minimum concentrations were measured in official and safeguarding station at 8.3 ± 2 and 0.012 ± 0.002 mg/m(3), respectively. Also, the maximum concentrations of respirable dust and free silica were measured in Tappeh Ghermez drilling no. 1 at 66 ± 13 and 1.5 ± 0.4 mg/m(3), respectively, while the minimum concentrations were measured in pneumatic hammer at 5.26 ± 3 and 0.01 ± 0.005 mg/m(3), respectively. Considerate to Iranian standard for respirable dust concentrations (0.11 mg/m(3)) and international standards (ACGIH = 0.1 and NIOSH = 0.05 mg/m(3)), it was found that dust and free silica amounts were much higher than national and international standard levels in this mine.