Modified Sol-Gel Synthesis of Mesoporous Borate Bioactive Glasses for Potential Use in Wound Healing.

In this study, we successfully utilized nitrate precursors for the synthesis of silver (Ag)-doped borate-based mesoporous bioactive glass (MBGs) based on the 1393B3 glass formulation in the presence of a polymeric substrate (polyvinyl alcohol (PVA)) as a stabilizer of boric acid. The X-ray diffraction (XRD) analysis confirmed the glassy state of all the MBGs. The incorporation of 7.5 mol% Ag into the glass composition led to a decrease in the glass transition temperature (Tg). Improvements in the particle size, zeta potential, surface roughness, and surface area values were observed in the Ag-doped MBGs. The MBGs (1 mg/mL) had no adverse effect on the viability of fibroblasts. In addition, Ag-doped MBGs exhibited potent antibacterial activity against gram-positive and gram-negative species. In summary, a modified sol-gel method was confirmed for producing the Ag-doped 1393B3 glasses, and the primary in vitro outcomes hold promise for conducting in vivo studies for managing burns.

Detection of Isoniazid and Rifampin Resistance in Mycobacterium tuberculosis Clinical Isolates from Sputum Samples by High-Resolution Melting Analysis.

The effective management of multidrug-resistant tuberculosis (MDR-TB) and the need for rapid and accurate screening of rifampin (RIF) and isoniazid (INH)-resistant Mycobacterium tuberculosis (Mtb) isolates are the most fundamental and difficult challenges facing the global TB control. The present study aimed to compare the diagnostic accuracy of high-resolution melting-curve analysis (HRMA) in comparison to multiplex allele-specific PCR (MAS-PCR) and xpert MTB/RIF as well as the conventional drug-susceptibility test (DST) and gene sequencing for the detection of INH and RIF resistance in the Mtb isolates. In the present study, a total of 431 Mtb isolates including 11 MDR (%2.55), 7 INH resistance (%1.62), two RIF resistance (%0.46), and 411 sensitive isolates were phenotypically confirmed. HRMA assay identified katG gene mutations and the mabA-inhA promoter region in 15 of 18 INH-resistant samples and rpoB gene mutations were successfully evaluated in 11 out of 13 RIF-resistant samples. The sensitivity and specificity of the HRMA method were 83.3% and 98.8% for INH and 84.6% and 99% for RIF, respectively. The most common mutation in RIF-resistance-determining region (RRDR) occurred at codon 531 (TCG → TTG)(84.6%) and then at codon 513 (CAA → GTA)(7.6%) and 526 (CAC → TAC) (7.6%), which resulted in the amino-acid changes. Also, 88.8% of INH-resistant samples had mutations in the katG gene and the mabA-inhA promoter region, of which the highest mutation occurred at codon 315 (AGC → ACC) of the katG gene. In conclusion, all these results indicated that the sensitivity and specificity of the HRM method were increased when the katG gene and the mabA-inhA promoter region were used as a target.

Decellularization of human amniotic membrane using detergent-free methods: Possibilities in tissue engineering.

The human amniotic membrane (HAM) is widely used as a natural scaffold in tissue engineering due to its excellent biological characteristics, including anti-microbial, anti-inflammatory, low immunogenicity, and pro-angiogenic properties. This study aimed to develop simple and cost-effective protocols for the decellularization of HAM (d-HAM) using detergent-free methods, i.e., mechanical force (brushing) and physical treatment (heating 45-55 °C). The effectiveness of the methods of interest was compared with a chemical-based approach (EDTA + NaOH + NH4Cl). The prepared d-HAMs were characterized using a series of physico-chemical, mechanical, and biological evaluations. The results from DAPI staining revealed that the chemical method could completely remove epithelial cells from HAM, while the two other approaches only reduced the number of epithelial cells. All three decellularization methods led to a sharp reduction (P < 0.001) in the DNA content of the tissue samples (< 50 ng/mg). Histological evaluations showed the preservation of the d-HAMs' integrity along with the conservation of collagen and glycosaminoglycans (GAGs). Although the chemical method caused the lowest mechanical deterioration (3.55 MPa in ultimate tensile stress), the mechanical method preserved the highest hydroxyproline levels (3.13 mg/mL). On the other hand, the physical method (heating to 45 and 50 °C) encouraged cell proliferation more than the chemical and mechanical approaches. All of the samples proved to be suitable for cell attachment and could induce cell migration. In conclusion, the present study showed that the use of detergent-free protocols is applicable for the decellularization of HAM, and the obtained tissues may be considered as inexpensive dressings for numerous tissue engineering applications.

Stem cell-mediated angiogenesis in skin tissue engineering and wound healing.

The timely management of skin wounds has been an unmet clinical need for centuries. While there have been several attempts to accelerate wound healing and reduce the cost of hospitalisation and the healthcare burden, there remains a lack of efficient and effective wound healing approaches. In this regard, stem cell-based therapies have garnered an outstanding position for the treatment of both acute and chronic skin wounds. Stem cells of different origins (e.g., embryo-derived stem cells) have been utilised for managing cutaneous lesions; specifically, mesenchymal stem cells (MSCs) isolated from foetal (umbilical cord) and adult (bone marrow) tissues paved the way to more satisfactory outcomes. Since angiogenesis plays a critical role in all four stages of normal wound healing, recent therapeutic approaches have focused on utilising stem cells for inducing neovascularisation. In fact, stem cells can promote angiogenesis via either differentiation into endothelial lineages or secreting pro-angiogenic exosomes. Furthermore, particular conditions (e.g., hypoxic environments) can be applied in order to boost the pro-angiogenic capability of stem cells before transplantation. For tissue engineering and regenerative medicine applications, stem cells can be combined with specific types of pro-angiogenic biocompatible materials (e.g., bioactive glasses) to enhance the neovascularisation process and subsequently accelerate wound healing. As such, this review article summarises such efforts emphasising the bright future that is conceivable when using pro-angiogenic stem cells for treating acute and chronic skin wounds.

Experience of patients hospitalized with COVID-19: A qualitative study of a pandemic disease in Iran.

BACKGROUND: The spread of COVID-19 as an infectious disease brings about many newly arrived challenges, which call for further research on the scope of its effect on life due to the special conditions of this disease. The present study is, therefore, an attempt to understand the lived experience of inpatients hospitalized with COVID-19. METHOD: In this phenomenological study, among patients with COVID-19 who were hospitalized in COVID-19 referral hospitals, 17 people were selected by random sampling method. Data were gathered by interviews and analysed using MAXQDA10 software. FINDINGS: Analysis revealed 4 main themes and 16 subthemes. Main themes included the (1) denial of the disease, (2) negative emotions upon arrival, (3) perception of social and psychological supports and (4) post-discharge concerns and problems. CONCLUSION: Patients with COVID-19 experience a different world of stresses, concerns and feelings in the course of their disease. Gaining a deeper insight into patients' experiences with this disease can help handle this disease more effectively and provide better post-corona nursing and psychological care and services.

Diagnostic and Therapeutic Costs of Patients With a Diagnosis of or Suspected Coronavirus Disease in Iran.

OBJECTIVES: To understand the social and individual effects of the disease and make decisions on the allocation of health resources, it is necessary to understand the economic burden of coronavirus disease (COVID-19); however, there are limited data in this field. This study aimed to estimate diagnostic and therapeutic costs of patients with a diagnosis of or suspected of COVID-19 disease admitted to hospitals in northeast Iran. METHODS: This descriptive and analytical research was conducted as a retrospective study using the data collected from 2980 patients admitted to 30 hospitals from February to April 2020 in Iran. For data collection, an appropriate data capture tool was designed to record detailed resource use. A multivariate regression analysis was performed to examine the association between the treatment costs and sociodemographic, disease severity, and underlying diseases. Data were analyzed using Excel 2017 (Microsoft, Redmond, WA) and SPSS version 21 software (SPSS Inc., Chicago, IL). RESULTS: The inpatient costs per patient were Int$416, of which 74% were paid by social health insurance systems, 19% by the government, and 7% by the patients. The largest cost components were hoteling (37%) and medicine (36%). The 4 subscales of age, sex, underlying disease, and severity predicted 48.6% of the cost variance. CONCLUSION: Understanding the economic consequences of diseases can help policymakers to make plans to reduce out-of-pocket payments and make plans for funding. Since COVID-19 is a newly emerging disease and there is no definitive cure for the disease, the discovery of an effective medicine may alter medical costs and reduce the hospital length of stay, therefore significantly reducing treatment costs.

Stem cell-based therapies for cardiac diseases: The critical role of angiogenic exosomes.

Finding effective treatments for cardiac diseases is among the hottest subjects in medicine; cell-based therapies have brought great promises for managing a broad range of life-threatening heart complications such as myocardial infarction. After clarifying the critical role of angiogenesis in tissue repair and regeneration, various stem/progenitor cell were utilized to accelerate the healing of injured cardiac tissue. Embryonic, fetal, adult, and induced pluripotent stem cells have shown the appropriate proangiogenic potential for tissue repair strategies. The capability of stem cells for differentiating into endothelial lineages was initially introduced as the primary mechanism involved in improving angiogenesis and accelerated heart tissue repair. However, recent studies have demonstrated the leading role of paracrine factors secreted by stem cells in advancing neo-vessel formation. Genetically modified stem cells are also being applied for promoting angiogenesis regarding their ability to considerably overexpress and secrete angiogenic bioactive molecules. Yet, conducting further research seems necessary to precisely identify molecular mechanisms behind the proangiogenic potential of stem cells, including the signaling pathways and regulatory molecules such as microRNAs. In conclusion, stem cells' pivotal roles in promoting angiogenesis and consequent improved cardiac healing and remodeling processes should not be ignored, especially in the case of stem cell-derived extracellular vesicles.

Serum Pro-oxidant-antioxidant Balance in Subjects with Type 2 Diabetes Mellitus.

AIM AND OBJECTIVE: Diabetes mellitus is associated with inflammation and increased oxidative stress. In the current study, we aimed to investigate the relationship between type 2 diabetes mellitus (T2DM) and serum pro-oxidant-antioxidant balance (PAB) in a large populationbased study. METHODS: In this cross-sectional study, 7888 individuals were recruited as part of the Mashhad Stroke and Heart Atherosclerotic Disorders (MASHAD) cohort study. Participants were divided into three groups based on their serum PAB values (levels < 36.4, 36.4-82.6 and > 82.6 HK). Serum PAB values were measured using a colorimetric method and enzyme-linked immune sorbent assay (ELISA). RESULTS: Serum PAB in subjects with and without diabetes was reported 76.85 ± 61.07 HK and 69.51 ± 55.50 HK. In subjects with a serum PAB > 82.6 HK the risk of T2DM was 1.2 fold higher in comparison to subjects with a serum PAB < 36.4 HK (OR: 1.26, 95% CI: 1.09 - 1.47, P-value: 0.002). This association remained significant after adjustment for confounding factors in multivariable analysis (OR: 1.19, 95% CI: 1.02 - 1.38, P-value: 0.027). CONCLUSION: Increased pro-oxidant levels may be a major complication of T2DM in our study subjects and PAB could be an indicator of higher oxidative stress in T2DM patients from northeastern Iran.

The effect of adipose-derived mesenchymal stem cells on renal function and histopathology in a rat model of ischemia-reperfusion induced acute kidney injury.

OBJECTIVES: It has been shown that adipose-derived mesenchymal stem cells (AD-MSC) have protective effects in acute kidney injury (AKI). This study was conducted to assess the therapeutic effects of AD-MSC in rats subjected to acute kidney injury by 45 min of renal ischemia followed by 48 hr of reperfusion (I/R). MATERIALS AND METHODS: 28 male Wistar rats were divided into four groups, including control, 48-hr sham, 48-hr I/R, and 48-hr I/R receiving AD-MSC. After 48 hr of reperfusion, blood samples were taken from rats' hearts, and 24-hr urines were collected using a metabolic cage. Serum creatinine level (Cr), blood urea nitrogen (BUN), creatinine clearance (Ccr), absolute sodium excretion (UNaV°), fractional sodium excretion (FENa), absolute potassium excretion (UKV°), factional potassium excretion (FEK), and urine osmolarity were measured. Malondialdehyde (MDA) and ferric reducing antioxidant power (FRAP) levels were measured in the right kidney, while the left kidney was used for histologic study after Hematoxylin-Eosin staining. RESULTS: Renal I/R significantly increased serum Cr, BUN, UNaV°, FENa, FEK, and tissue MDA, and significantly decreased Ccr and urine osmolarity as compared with the sham group. Moreover, histologic studies showed that I/R increased Bowman capsule area, tubular necrosis, vascular congestion, and caused formation of intratubular casts. Administration of AD-MSC at the time of I/R completely or partially protected kidneys from these I/R induced injuries. CONCLUSION: Our results show that injection of AD-MSC can reduce degree of renal injury caused by 45 min of ischemia followed by 48 hr of reperfusion in rats.

Quantum Dots: A Review from Concept to Clinic.

Quantum dots (QDs) are semiconductor materials that have gained great interest due to their unique characteristics like optical properties. They are extensively being used in different areas, including solar cells, light-emitting diodes, laser technology, as well as biological and biomedical applications. In this review, comprehensive information about different aspects of QDs is provided, including their types and classifications, synthesis approaches, in vitro and in vivo toxicity, biological applications, and potentials in clinical applications. With a focus on the biological aspects, the respective in vitro and in vivo studies are collected and presented. Various surface modifications on QDs are discussed as directly influencing their properties like toxicity and optical abilities. Given the promising results, these materials are clinically used for targeted molecular therapy and imaging. However, there are a large number of questions that should be addressed before the wide application of QDs in a clinical setting. Regarding the existing barriers to QDs, suggestions are given and discussed to present an appropriate route for the clinical use of these materials.

Fibroblast Growth Factor 1 Gene-Transfected Adipose-Derived Mesenchymal Stem Cells Modulate Apoptosis And Inflammation In The Chronic Constriction Injury Model of Neuropathic Pain.

Stem cell therapy is noted for its clinical effect in the treatment of neuropathic pain. This study aimed to investigate the potential anti-apoptotic and anti-inflammatory effects of adipose-derived mesenchymal stem cells (AD-MSCs) and fibroblast growth factor 1 gene-transfected adipose-derived mesenchymal stem cells (AD-MSCs FGF1) on chronic constriction injury (CCI) of the rat's sciatic nerve. The rats that underwent CCI were treated with AD-MSCs and AD-MSCs FGF1. Bax, Bcl2, and caspases 3, the major contributors of apoptosis, and inflammatory markers including Iba-1, IL1-ß, and MMP-2 were evaluated in the lumbar portion (L4-L6) of the spinal cord through western bloating at days 3 and 14. The ratio of Bax/Bcl2, cleaved caspases 3, MMP-2, IL-1ß, and Iba1, was elevated in CCI animals compared to sham-operated animals and decreased following treatment with both AD-MSCs and AD-MSCs FGF1. However, the effect of AD-MSCs FGF1 was significantly higher than AD-MSCs. These data suggest that the administration of AD-MSCs FGF1 through modulating apoptosis and neuroinflammation could be considered a promising medicine for treating neuropathic pain.

Altered serum Zinc and Copper in Iranian Adults who were of normal weight but metabolically obese.

Metabolically obese normal weight (MONW) individuals are potentially at increased risk of developing metabolic syndrome. Serum zinc and copper concentrations were assessed in individuals with MONW to determine whether MONW is associated with altered serum zinc and/or copper status. Normal weight subjects (total n = 2419; 1298 men and 1121 women), were recruited as part of Mashhad Stroke and Heart Association Disorder (MASHAD) Study cohort. They were divided into two groups according to the presence or absence of MetS, defined using IDF criteria. Serum zinc and copper concentrations were determined by atomic absorption. Of the 2419 normal weight adults, 377 had MetS. Of this group, 53.7% and 49.7% had a serum zinc <70 µg/dl (Q1) (p = 0.001) or a serum copper <79 µg/dl (Q1) respectively. Furthermore, 27.3% had a serum copper >131 µg/dl (Q4) (p = 0.034), and 18.8% had a serum zinc >95 µg/dl (Q4). Logistic regression analysis was performed to determine the odds ratio (OR) for an association of serum zinc, copper and zinc to copper ratio with MetS in normal weight subjects. The subjects with a serum zinc >95 µg/dl (Q4) had 0.386 [OR: 0.614(95%CI 0.457-0.823)] lower chance of MetS (p = 0.001) and the subjects with a serum copper >131 (Q4) had OR 1.423 (95% CI: 1.09-1.857) higher chance of MetS (p = 0.009). These data remained significant after adjustment for age and sex, for serum zinc and copper, respectively. Furthermore, our results strongly suggested that zinc and copper were the independent risk factor for metabolic syndrome in normal weight subjects. There is an imbalance between serum copper and zinc concentrations among individuals with MONW when compared with normal BMI individuals without MetS. This may increase the risk of individuals with MONW developing conditions associated with this imbalance, such as diabetes and cardiovascular disease.

Curcumin: footprints on cardiac tissue engineering.

Introduction: Curcumin-based products are extensively used as therapeutics in the treatment of cardiac disorders; however, there is no significant report on the curcumin potentials in cardiac tissue engineering applications. Due to its anti-oxidant, anti-inflammatory, and anti-apoptotic properties, curcumin has been demonstrated to be a promising candidate for tissue engineering (TE) applications. Areas covered: Various curcumin-containing tissue-engineered constructs have been developed for the management of soft tissue damages (such as wound injuries); hence, there are hopes for the use of this natural product in cardiac tissue engineering (CTE). However, some crucial issues should primarily be addressed before curcumin could be widely used in CTE. Expert opinion: The challenges regarding the use of curcumin in CTE include the optimum dosages of curcumin for promoting cardiac regeneration, the type of carrier used (e.g., polymeric matrices), the preferable release profile, as well as the short- and long-term toxicity in the human body.

Biomedical applications of nanoceria: new roles for an old player.

The use of different biomaterials with the ability to accelerate the repair and regeneration processes is of great importance in tissue engineering strategies. On this point, cerium oxide nanoparticles (CNPs or nanoceria) have recently attracted much attention due to their excellent biological properties including anti-oxidant, anti-inflammation and antibacterial activities as well as high angiogenic potential. The results of incorporation of these nano-sized particles into various constructs and scaffolds designed for tissue engineering applications have proven the success of this strategy in terms of improving healing process of different tissues. In this review, we first summarize the physicochemical and biological properties of nanoceria in brief and then present its usability in tissue engineering strategies based on the currently available published reports.

Fibroblast Growth Factor Type 1 (FGF1)-Overexpressed Adipose-Derived Mesenchaymal Stem Cells (AD-MSCFGF1) Induce Neuroprotection and Functional Recovery in a Rat Stroke Model.

Stroke, as the second most common cause of death, imposes a great financial burden on both the individual and society. Mesenchymal stem cells from rodents have demonstrated efficacy in experimental animal models of stroke due to enhanced neurological recovery. Since FGF1 (fibroblast growth factor 1) displays neuroprotective properties, for the first time, we investigated the effect of acute intravenous administration of FGF1 gene transfected adipose-derived mesenchymal stem cell (AD-MSCFGF1) on transient experimental ischemic stroke in rats. Stroke induction was made by transient middle cerebral artery occlusion (tMCAO). 2 × 106 AD-MSCFGF1 was administrated intravenously 30 min after carotid reperfusion. The ability of technetium99m-hexamethyl propylene amine oxime (99mTc-HMPAO)-labeled AD-MSCFGF1 to enter into ischemic brain was evaluated 2 h post injection. 24 h post operation, the neurological recovery (rotarod and Roger's tests), the infarct volume (2, 3, 5-triphenyltetrazolium chloride, TTC assay), apoptosis rate (TUNEL assay), and the expression of FGF1 protein (western blotting) in the ischemic hemisphere were assessed. The 99mTc-HMPAO-labeled AD-MSCFGF1 could enter into the ischemic brain. Ischemic hemisphere activity was significantly higher than that observed in the contralateral hemisphere (p = 0.002). The administration of AD-MSCFGF1 resulted in significant improvement of neurological function tests and increased density of FGF1 protein in the peri-infarct area, while the infarct volume and the apoptotic index were significantly decreased, in comparison to the other treated groups. In conclusion, acute intravenous administration of AD-MSCFGF1 can be a novel and promising candidate approach for the treatment of ischemic stroke.

Platelet rich plasma: Effective treatment for repairing of spinal cord injury in rat.

OBJECTIVE: The aim of the present study was to evaluate the effect of PRP on the repair of spinal cord injury in rat model. MATERIAL AND METHODS: Rats were randomly divided into three groups with six rats in each group. Then, spinal cord injury was performed under general anesthesia using "weight dropping" method. Control group included rats receiving normal saline, group two received PRP 1 week after injury; group three received PRP 24 h after injury. The motor function was assessed weekly using the Basso, Beattie, and Bresnahan (BBB) locomotor rating scale. Anterograde tracing was performed for evaluation of axon regeneration. RESULT: Motor recovery was significantly better in the rats treated with PRP 24 h after injury than the control group. In the rats treated with PRP 1 week after injury and rats treated with PRP 24 h after injury, the average numbers of BDA-labeled axons were statistically different from the control group. CONCLUSION: Our experimental study demonstrated positive effects of platelet rich plasma on nerve regeneration after spinal cord injury.

Fibroblast Growth Factor 1-Transfected Adipose-Derived Mesenchymal Stem Cells Promote Angiogenic Proliferation.

The aim of this study was to investigate, for the first time, the effects of using adipose-derived mesenchymal stem cells (AD-MSCs) transfected with an episomal plasmid encoding fibroblast growth factor 1 (FGF1) (AD-MSCsFGF1), in providing the microenvironment required for angiogenic proliferation. The isolated rat AD-MSCs were positive for mesenchymal (CD29 and CD90) and negative for hematopoietic (CD34 and CD45) surface markers. Adipogenic and osteogenic differentiation of the AD-MSCs also occurred in the proper culture media. The presence of FGF1 in the conditioned medium from the AD-MSCsFGF1 was confirmed by Western blotting. G418 and PCR were used for selection of transfected cells and confirmation of the presence of FGF1 mRNA, respectively. Treatment with the AD-MSCFGF1-conditioned medium significantly increased the NIH-3T3 cell proliferation and human umbilical vein endothelial cell (HUVEC) tube formation compared to conditioned medium from nontransfected AD-MSCs (p < 0.001). In conclusion, the AD-MSCsFGF1 efficiently secreted functional FGF1, which promoted angiogenic proliferation. Using AD-MSCsFGF1 may provide a useful strategy in cell therapy, which can merge the beneficial effects of stem cells with the positive biological effects of FGF1 in various disorders, especially tissue defects, neurodegenerative, cardiovascular and diabetes endocrine pathologies, which remain to be tested in preclinical and clinical studies.

Effects of Streptozotocin-Induced Diabetes on Proliferation and Differentiation Abilities of Mesenchymal Stem Cells Derived from Subcutaneous and Visceral Adipose Tissues.

Introduction: Accumulated evidence indicates that there are intrinsic differences between adipose tissue-derived stem cells (ASCs) obtained from different body fat depots. Here, we compared the proliferation and multipotency of subcutaneous ASCs (SC-ASCs) and epididymal ASCs (ED-ASCs) before and after induction of diabetes by streptozotocin. Methods: The adipogenic and osteogenic abilities of rat SC-ASCs and ED-ASCs were evaluated using Oil Red O and Alizarin Red staining, respectively. The expression of adipocyte (PPAR-γ, LPL) and osteoblast (ALP, SPP1) specific mRNAs was evaluated by quantitative real-time PCR. MTT test was used for determination of cell proliferation capacity. Results: The proliferation of SC-ASCs was higher than ED-ASCs, both before and after diabetes induction (P<0.05). Diabetes increased the proliferative capability of SC-ASCs (P<0.05) but not ED-ASCs. Before diabetes, both adipogenic and osteogenic differentiation of SC-ASCs were higher than ED-ASCs (P<0.05). After diabetes, both SC-ASCs and ED-ASCs were able to differentiate into adipocyte and osteoblast, but the levels of differentiation were higher in SC-ASCs than in ED-ASCs (P<0.05). Diabetes decreased the expression of PPAR-γ and LPL, but increased the SPP1 and ALP expression in both SC-ASCs and ED-ASCs. Conclusion: Our data suggested that diabetes increases the proliferation of ASCs but decreases their adipogenic differentiation. Also, SC-ASCs have higher proliferation and differentiation abilities than ED-ASCs in normal and diabetic conditions so can be more preferable for cell therapy.