Regenerative engineering of long bones using the small molecule forskolin.

Bone grafting procedures have become increasingly common in the United States, with approximately 500,000 cases occurring each year at a societal cost exceeding $2.4 billion. Recombinant human bone morphogenetic proteins (rhBMPs) are therapeutic agents that have been widely used by orthopedic surgeons to stimulate bone tissue formation alone and when paired with biomaterials. However, significant limitations such as immunogenicity, high production cost, and ectopic bone growth from these therapies remain. Therefore, efforts have been made to discover and repurpose osteoinductive small-molecule therapeutics to promote bone regeneration. Previously, we have demonstrated that a single-dose treatment with the small-molecule forskolin for just 24 h induces osteogenic differentiation of rabbit bone marrow-derived stem cells in vitro, while mitigating adverse side effects attributed with prolonged small-molecule treatment schemes. In this study, we engineered a composite fibrin-PLGA [poly(lactide-co-glycolide)]-sintered microsphere scaffold for the localized, short-term delivery of the osteoinductive small molecule, forskolin. In vitro characterization studies showed that forskolin released out of the fibrin gel within the first 24 h and retained its bioactivity toward osteogenic differentiation of bone marrow-derived stem cells. The forskolin-loaded fibrin-PLGA scaffold was also able to guide bone formation in a 3-mo rabbit radial critical-sized defect model comparable to recombinant human bone morphogenetic protein-2 (rhBMP-2) treatment, as demonstrated through histological and mechanical evaluation, with minimal systemic off-target side effects. Together, these results demonstrate the successful application of an innovative small-molecule treatment approach within long bone critical-sized defects.

Adherence to the Mediterranean diet and risk of gestational diabetes: a prospective cohort study.

BACKGROUND: Limited data is available on the association between adherence to the Mediterranean diet during early pregnancy and risk of gestational diabetes (GDM) in countries located in the Middle East, one of the regions with the highest prevalence of GDM. METHODS: A total of 647 pregnant mothers were included in the present prospective birth cohort study in Iran. Dietary intake was assessed by a 90-item food frequency questionnaire during the first trimester of pregnancy. Cases of GDM were ascertained by a two-step approach with a 50-g screen followed by a 100-g oral glucose tolerance for those who tested positive. Cox proportional hazard model was used to calculate the hazard ratio and 95%CI of GDM across tertiles of the Mediterranean diet score, while controlling for a wide range of potential confounders. RESULTS: A total of 647 pregnant mothers were included, of whom 77 mothers were diagnosed with GDM during their pregnancy. The average age of the mothers was 28.8 ± 5.1 years. In the multivariable analysis, being in the third tertile of the score of adherence to the Mediterranean diet was associated with a 41% lower risk of developing GDM as compared to those in the first tertile (adjusted hazard ratio: 0.59, 95%CI: 0.35, 0.99). CONCLUSIONS: Based on our findings, greater adherence to the Mediterranean diet during early pregnancy may be associated with a lower risk of developing GDM in Iranian women. Larger cohort studies are needed to confirm the findings.

Polyvinyl alcohol/citric acid/ß-cyclodextrin/CuONP composite nanofibers as an effective and green absorbent for the simultaneous extraction of three antidepressant drugs in biological fluids prior to GC-FID analysis.

Composite nanofibers, namely, polyvinyl alcohol (PVA), citric acid (CA), ß-cyclodextrin (ß-CD), and copper oxide nanoparticles (PVA/CA/ß-cyclodextrin/CuO NPs), were developed as a novel, green, and efficient adsorbent in the pipette tip-micro-solid-phase extraction method (PT-µSPE), for the simultaneous extraction of three antidepressants drugs namely imipramine (IMP), citalopram (CIT), and clozapine (CLZ) in biological fluids before quantification by gas chromatography (GC-FID). Based on the obtained results from field emission scanning electron microscopy (FE-SEM), energy-dispersive X-ray spectroscopy (EDX), Fourier transform infrared spectroscopy (FT-IR), and X-ray diffraction (XRD), the successful synthesis of composite nanofibers was approved. Due to the presence of ß-cyclodextrins and CuO NPs rich of functional groups on their surface, the nanofibers have high extraction efficiency. Under the optimal conditions, the linear range for imipramine, citalopram, and clozapine was 0.1 to 1000.0 ng mL-1 with a determination coefficient ≥ 0.99. The limits of detection (LODs) were in the range 0.03 to 0.15 ng mL-1. The relative standard deviation was 4.8 to 8.7% (within-day, n = 4) and 5.1 to 9.2% (between-day, n = 3) for 3 consecutive days. In addition, excellent clean-up was achieved which is a great advantage over other sample preparation methods. Finally, the ability of the developed method to extract the target analytes from the biological samples was evaluated.

The Role of the Health Belief Model in Explaining Why Symptomatic Iranian Women Hesitate to Seek Early Screening for Breast Cancer: a Qualitative Study.

Early detection of breast cancer (BC) is important to increase the likelihood of treatment and improve the quality of life and survival. The study explored why symptomatic women linger to seek early screening for BC diagnosis based on the health belief model (HBM). In this qualitative study, 20 participants were selected using the purposive sampling method (9 health professionals and 11 female patients BC). Data were collected using in-depth, semi-structured interviews in 2019. Transcribed interview data were analyzed using the directed content analysis informed by HBM. According to the participants' experiences, although most patients comprehended the extent of the disease, they did not see themselves at risk of BC. Some were not adequately aware of the benefits of early diagnosis and did not have the self-efficacy required for early presentation. The main barriers to the early presentation included lack of awareness, financial problems, embarrassment over the clinical examination, and inadequate access to specialized centers. According to HBM, while designing and implementing educational programs, it is recommended to focus on reinforcing perceived susceptibility, perceived benefits, and perceived self-efficacy, providing access to facilities, and removing possible barriers and cultural issues to encourage women for timely referral for BC screening.

Food Quality Score and Risk of Breast Cancer among Iranian Women: Findings from a Case Control Study.

The quality of foods we consume may be an important risk factor for breast cancer (BrCa); however, relations between quality of food metrics and BrCa risk have not been systematically investigated. The purpose of this study was to examine the association between food quality score (FQS) by assessing the intake of healthy and unhealthy food and the odds of (BrCa) among Iranian women. This hospital-based case-control study was carried out on 150 women with pathologically confirmed breast cancer within the past three months and 150 healthy controls that were age-match from the Cancer Research Center, Imam Khomeini hospital, Iran. Participants were interviewed to obtain data relating to diet (using a 147-item validated FFQ) and BrCa risk factors. We found a significant association between adherence to the FQS and odds of breast cancer in the fully adjusted model (OR: 0.58; P = 0.04) and in premenopausal women in the fully adjusted model (OR: 0.45; P = 0.02); however, we did not observe any association between postmenopausal women in the adjusted model (OR: 0.76; P = 0.5). We also failed to observe any association between healthy (p = 0.3) and unhealthy subgroups (p = 0.3) of FQS. Our findings suggest that adherence to FQS may be associated with an increased risk of breast cancer in crude and adjusted models in overall and premenopausal women. However, we did not see any association between FQS and BrCa risk in postmenopausal women. Prospective cohort studies are needed to confirm these findings.Supplemental data for this article is available online at https://doi.org/10.1080/01635581.2021.1957136 .

Dietary Carbohydrate Quality and Quantity and Risk of Breast Cancer among Iranian Women.

OBJECTIVE: This study investigated the association between quality and quantity of carbohydrate by assessing low carbohydrates diet score (LCDS), carbohydrate quality score (CQI), glycemic index (GI), dietary glycemic load (GL), and dietary carbohydrate intake, and risk of breast cancer (BrCa) among Iranian women. METHODS: This hospital-based case-control study was carried out in the Cancer Research Center of Imam Khomeini hospital, Iran. We included One hundred and fifty newly diagnosed BrCa cases and one hundred and fifty healthy controls in this study. Socio-demographic and dietary data and anthropometric measures were recorded. RESULTS: We found that a higher CQI than a lower score was associated with a decrease in odds of BrCa (P = 0.04). After adjusting for potential confounders, we observed that CQI was not associated with BrCa development (P = 0.05). An increase in odds of BrCa among women in the highest tertiles of GL (P = 0.12), GI (P = 0.48), and dietary carbohydrate intake (P = 0.06) was seen, which was not statistically significant. There was also a non-significant lower chance of having BrCa with adherence to the LCDS (P = 0.09). CONCLUSION: Our findings suggest that CQI was not related to BrCa risk among Iranian women. This relation deserves to be investigated in prospective studies.

Ambient air pollutants and respiratory health outcomes in Tabriz and Urmia, two metropolises of Iran.

Polluted air affects human life and it is crucial to assess air pollutants to inform policy and protect human lives. In this study, we sought to assess the respiratory outcomes associated with PM10, O3, SO2, and NO2 in the Iranian population. The required data, which included concentrations of air pollutants, meteorology, and population size, were obtained from the department of environment and meteorological organizations. The validity of the data was evaluated, and appropriate calculations were conducted on the data to extract the required values and parameters for modeling (using the AirQ2.2.3). This study was conducted in two megacities of Iran (Tabriz and Urmia) with over 2 million population. The annual averages of SO2, NO2, and PM10 concentrations were 9, 73, and 43 µg/m3 in Tabriz and 76, 29, and 76 µg/m3 in Urmia, respectively. Excess deaths from respiratory diseases associated with PM10 and SO2 were estimated to be 33.1 and 1.2 cases in Tabriz and 31.6 and 24.7 cases in Urmia, respectively. The proportions of hospitalizations for chronic obstructive pulmonary disease (COPD) attributable to SO2 and NO2 in Tabriz were 0.07% and 1.61%, respectively, whereas they were 2.84% and 0.48% in Urmia. O3 had an annual average of 56 µg/m3 in Tabriz and with 44.5 excess respiratory deaths and 42.5 excess hospital admissions for COPD, it had the greatest health impacts among the pollutants studied. Findings from this study add to the growing literature, especially from developing countries, that provides insights to help authorities and decision-makers develop and implement effective interventions to curb air pollution and save lives.

Factor affecting the activities of daily living among aging people during the COVID-19 pandemic - a structural equation modelling.

Introduction: The activities of daily living (ADLs) are a set of basic skills necessary for self-care. The inability of elderly people to perform ADLs leads to dependence, insecure conditions, and poor quality of life. The COVID-19 pandemic has affected all aspects of the daily life of the elderly. This study aimed to determine the factors associated with ADLs among elderly people during the COVID-19 pandemic using structural equation modelling/path analysis. Material and methods: It was a descriptive-analytical study which had conducted on 487 elderly people who were selected randomly to participate in the study. Data collection tools included a demographic information questionnaire, an activities of daily living questionnaire, a knee pain and personal performance questionnaire Western Ontario and McMaster Universities Osteoarthritis (WOMAC), and the falls efficacy scale, which were completed by interview and self-report methods. SPSS-22 and AMOS software were used for data analysis. Results: Two structures of the fear of falling (FOF) and knee pain and personal performance questionnaire WOMAC had a significant role in explaining the ADL variance among the studied elderly people (p < 0.001, root mean square error of approximation = 0.063). These variables explained 64% of the ADL variance. Conclusions: The structures of this model (FOF and WOMAC) can be used as a reference framework to design effective interventions for improving ADLs among elderly people during the COVID-19 epidemic. It is also recommended that a multi-component program be provided, which includes exercise and psychological strategies for this population during the COVID-19 pandemic through online videos, distance health programs, etc.

Ligand-Controlled Csp2-H versus Csp3-H Bond Formation in Cycloplatinated Complexes: A Joint Experimental and Theoretical Mechanistic Investigation.

The cyclometalated platinum(II) complexes [PtMe(C∧N)(L)] [1PS: C∧N = 2-phenylpyridinate (ppy), L = SMe2; 1BS: C∧N = benzo[h]quinolate (bhq), L = SMe2; 1PP: C∧N = ppy, L = PPh3; and 1BP: C∧N = bhq, L = PPh3] containing two different cyclometalated ligands and two different ancillary ligands have been investigated in the reaction with CX3CO2H (X = F or H). When L = SMe2, the Pt-Me bond rather than the Pt-C bond of the cycloplatinated complex is cleaved to give the complexes [Pt(C∧N)(CX3CO2)(SMe2)]. When L = PPh3, the selectivity of the reaction is reversed. In the reaction of [PtMe(C∧N)(PPh3)] with CF3CO2H, the Pt-C∧N bond is cleaved rather than the Pt-Me bond. The latter reaction gave [PtMe(κ1N-Hppy)(PPh3)(CF3CO2)] as an equilibrium mixture of two isomers. For L = PPh3, no reaction was observed with CH3CO2H. The reasons for this difference in selectivity for complexes 1 are computationally discussed based on the energy barrier needed for the protonolysis of the Pt-Csp3 bond versus the Pt-Csp2 bond. Two pathways including the direct one-step acid attack at the Pt-C bond (SE2) and stepwise oxidative-addition on the Pt(II) center followed by reductive elimination [SE(ox)] are proposed. A detailed density functional theory (DFT) study of these protonations along with experimental UV-vis kinetics suggests that a one-step electrophilic attack (SE2) at the Pt-C bond is the most likely mechanism for complexes 1, and changing the nature of the ancillary ligand can influence the selectivity in the Pt-C bond cleavage. The effect of the nature of the acid and cyclometalated ligand (C∧N) is also discussed.

The association between adherence to MIND diet and risk of breast cancer: A case-control study.

OBJECTIVES: Recently, a new eating pattern called "Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND)" has been coined. This study was aimed to examine the association between adherence to the MIND diet and risk of breast cancer (BC) among Iranian women. METHODS: In this hospital-based case-control study, 150 newly diagnosed BC cases and 150 age-matched controls were included. All cases were pathologically confirmed BC patients, with no history of any type of other pathologically confirmed cancers. Controls were selected from visitors, relatives and friends of non-cancer patients in other wards, which had no family relationship with cases. Dietary intakes of study participants were assessed using a validated 147-item semi-quantitative food frequency questionnaire (FFQ). The MIND diet score was computed based on participants' dietary intakes obtained from FFQ, Regression logistic models were used to examine the association between the MIND diet score and BC. RESULTS: Examining the whole study population, we found no significant association between the MIND diet score and odds of BC, either before (ORs for comparing T3 vs. T1: 0.818; 95% CI: 0.469-1.42, P-trend = .48) or after controlling for potential confounders (ORs for T3 vs. T1: 1.32; 95% CI: 0.31-5.64, P-trend = .633). This was also the case for pre-menopausal and post-menopausal when analyzed separately. We also failed to find any significant association between the MIND diet score and odds of BC after controlling for potential confounders in both pre-menopausal and post-menopausal. CONCLUSION: In conclusion, we found that adherence to the MIND diet was not associated with odds of BC in this case-control study. Further studies are required to confirm these findings.

Total and drinking water intake and risk of all-cause and cardiovascular mortality: A systematic review and dose-response meta-analysis of prospective cohort studies.

BACKGROUND: Understanding the association between water consumption and mortality is important for guiding consumers and prioritizing dietary guidelines to reduce the risk. Therefore, in the current study, we conducted a systematic review and dose-response meta-analysis of prospective cohort studies to summarise the association between total water and drinking intake and risk of mortality from all causes and CVD. METHOD: A comprehensive search was performed on PubMed/Medline, Scopus, and ISI Web of Science up to February 2020. The random-effects model was used to calculate the pooled effect size (ES) and 95% confidence interval. RESULT: Seven prospective cohort studies were included in the systematic review and meta-analysis. During the follow-up period of 6 to 19.1 years, 14 754 deaths (7611 from cardiovascular disease) occurred among 116 816 participants. No significant association was found between drinking water intake and all-cause mortality (ES: 0.82; 95% CI: 0.63-1.08, I2  = 77.3%, P = .16). Total water intake was not associated with all-cause mortality (ES: 0.94; 95% CI: 0.82-1.08, I2  = 66.5%, P = .41). However, a significant inverse association was seen between total water intake and risk of CVD mortality (ES: 0.86; 95% CI: 0.78-0.95, I2  = 0%, P = .002). Linear dose-response meta-analysis revealed a significant inverse association between total water intake and all-cause mortality by an additional one cup per day (pooled ES: 0.98; 95% CI: 0.97-0.99, P = .001). Furthermore, each additional cup of total water intake per day was associated with a 3% lower risk of death from CVD (pooled ES: 0.97; 95% CI: 0.96-0.98, P < .001). CONCLUSION: High consumption of total water is associated with a lower risk of CVD mortality. However, total water intake was not associated with risk of all-cause mortality.

Dropout of infertility treatments and related factors among infertile couples.

BACKGROUND: Dropout of infertility treatments is a global issue and many factors play role in this phenomenon. It is one of the most challenges in life of infertile couples. The purpose of this study was to determine dropout rate and related factors/reasons in the world and in Iran. METHODS: We will conduct a mixed method study with sequential exploratory design (systematic review, qualitative and quantitative phase). In the first stage a systematic review on dropout rate of infertility treatments and related factors will be done. In second stage (quantitative-qualitative study), a retrospective cohort study will be conducted on infertile couples to determine dropout rate of infertility treatments. The follow-up period to assess the discontinuation of treatment in patients, who have discontinued the treatment, will be considered 6 months after the treatment cessation. Data would be analyzed by descriptive statistics. We want to determine proportion and percentage of discontinuation rate among different groups with different causes of infertility. Then, we also will use Chi-square test to compare discontinuation rates among these groups. In qualitative section of second stage, semi-structured interviews would be performed with infertile female who had the history of infertility treatments failure. In this stage, participants will be selected using purposeful sampling method with maximum variation in terms of age, education, occupation, type of infertility, type of treatments, number of unsuccessful treatment and infertility duration. Data would be analyzed using conventional content analysis. DISCUSSION: Determining dropout rate and its related factors/reasons would be helpful for future studies to plan suitable interventions for supporting infertile couples. It also helps politicians to have a better understanding of infertility and its consequences on infertile couple's life. In today's world, infertility is a common phenomenon due to postponement of childbearing following the older age of marriage, tendency to reach higher educational level, economical problems and etc. Infertility brings many challenges and stresses to the individuals by itself and it is very hard to cope with. The problem gets worse, when it is associated with failure in treatments. Many of infertile couples cannot tolerate this failure and may decide to discontinue treatments before achieving pregnancy for ending many stressors which are associated with treatments. As we know, childbearing and having at least one child has important position in some societies such as Iranian culture; so ending the treatment before achieving optimal result may have some adverse consequences in the families such as divorce, remarriage, family conflicts, et. Absolutely many factors play role in dropout of infertility treatments, and many studies around the world have suggested many factors/reasons in dropout of infertility treatments, but there are still many gaps about this subject, especially among Iranian society. This study would be conducted in three consecutive stages, in the first stage; we will do a complete review of existing studies of the world to find out related factors/reasons of dropout in detail. In second stage, dropout rate of infertile couples (380 couples) after at least one unsuccessful cycle of treatment would be achieved by assessing medical records and telephone interview. Data of the first and second stage will help us to have better vision about the issue of dropout and would be used to construct a semi structured interview for the last stage. And finally in the third stage, reasons of dropout would be asked by an in depth interview from infertile couples. We hope the information from this study will help politicians better understand and plan for dropout of treatment.

Adipose-derived stem cells-conditioned medium improved osteogenic differentiation of induced pluripotent stem cells when grown on polycaprolactone nanofibers.

Considering that the common osteogenic growth factors cannot be transplanted with stem cells to the patients, many studies are underway to find a replacement for these factors. Recently, it has been determined that mesenchymal stem cell (MSC)-derived conditioned medium (CM) contains effective factors in the bone formation process. In the current study, the synergistic effect of adipose-derived MSC's CM, and polycaprolactone (PCL) scaffold was investigated on the osteogenic differentiation potential of human induced pluripotent stem cells (iPSCs). After scaffold fabrication by electrospinning and characterization by scanning electron microscopy, iPSCs proliferation in the presence of CM, PCL, and both was evaluated using 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide. Then, iPSCs osteogenic differentiation was investigated while cultured on tissue culture plate and PCL under CM compared with the osteogenic medium using alizarin red staining, calcium content, alkaline phosphatase activity and gene and protein expression analysis. Proliferation rate of the iPSCs was increased while cultured under CM and its effect was synergistically enhanced by culture on PCL. Evaluation of the osteogenic markers was showed CM alone could induce osteogenic differentiation into the iPSCs and this potential was significantly increased while combined with PCL nanofibrous scaffold. According to the results, it was demonstrated that CM has an osteogenic induction property almost the same of the common osteogenic medium and it can also be used potentially with stem cells when transplant to the patients. CM can also help by prolonging cell survival at the site of the defect as well as accelerating healing process.

Efficient osteogenic differentiation of the dental pulp stem cells on ß-glycerophosphate loaded polycaprolactone/polyethylene oxide blend nanofibers.

Hard tissue lesion treatment in oral and maxillofacial has been challenging because of tissue complexities. This study aimed to investigate novel biopolymeric construct effects on the osteogenic differentiation potential of the dental pulp stem cells (DPSCs) for introducing a cell copolymer bioimplant. A blended polycaprolactone (PCL)-polyethylene oxide (PEO) was fabricated using electrospinning, simultaneously filled by ß-glycerophosphate (ß-GP). After that biocompatibility and release kinetics of the PCL-PEO+ß-GP was evaluated and compared with PCL-PEO and then the osteogenic differentiation potential of the DPSCs was examined while being cultured on the scaffolds and compared with those cultured on the culture plate. The results demonstrated that scaffolds have not any cytotoxicity and ß-GP can release in a long-term manner. Alkaline phosphatase activity and calcium content were significantly increased in DPSCs while being cultured on the PCL-PEO+ß-GP compared with the other groups. Runt-related transcription factor 2, collagen type-I, osteonectin, and osteocalcin (OSC) genes expression was upregulated in DPSCs cultured on the PCL-PEO+ß-GP and was significantly higher than those cultured on the PCL-PEO. Immunocytochemistry result also confirmed the positive effects of PCL-PEO+ß-GP on the osteogenic differentiation of the DPSCs by presenting a higher OSC protein expression. According to the results, incorporation of the ß-GP in PCL-PEO makes a better construct for osteogenic induction into the stem cells and it could be also considered as a great promising candidate for bone, oral, and maxillofacial tissue engineering applications.

Poly (3-hydroxybutyrate-co-3-hydroxyvalerate) improved osteogenic differentiation of the human induced pluripotent stem cells while considered as an artificial extracellular matrix.

Cocell polymers can be the best implants for replacing bone defects in patients. The pluripotent stem cells produced from the patient and the nanofibrous polymeric scaffold that can be completely degraded in the body and its produced monomers could be also usable are the best options for this implant. In this study, electrospun poly (3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) nanofibers were fabricated and characterized and then osteogenic differentiation of the human-induced pluripotent stem cells (iPSCs) was investigated while cultured on PHBV scaffold. MTT results showed that cultured iPSCs on PHBV proliferation were increased compared to those cultured on tissue culture polystyrene (TCPS) as the control. Alkaline phosphatase (ALP) activity and calcium content were also significantly increased in iPSCs cultured on PHBV compared to the cultured on TCPS under osteogenic medium. Gene expression evaluation demonstrated that Runx2, collagen type I, ALP, osteonectin, and osteocalcin were upregulated in iPSCs cultured on PHBV scaffold in comparison with those cultured on TCPS for 2 weeks. Western blot analysis have shown that osteocalcin and osteopontin expression as two major osteogenic markers were increased in iPSCs cultured on PHBV scaffold. According to the results, nanofiber-based PHBV has a promising potential to increase osteogenic differentiation of the stem cells and iPSCs-PHBV as a cell-co-polymer construct demonstrated that has a great efficiency for use as a bone tissue engineered bioimplant.

Promoting osteogenic differentiation of human-induced pluripotent stem cells by releasing Wnt/ß-catenin signaling activator from the nanofibers.

Implants that can enhance the stem cells differentiation in the absence of the chemical osteogenic growth factors will attract the great interest of orthopedic scientists. Inorganic polyphosphate (poly-P), as a ubiquitous biological polymer, is one of the factors that can be an alternative for osteogenic growth factors via activating Wnt/ß-catenin signaling. In this study, poly-P was incorporated at the blend of polycaprolactone (PCL)/poly (l-lactic acid) (PLLA) electrospun nanofibers and then osteogenic differentiation potential of human-induced pluripotent stem cells (iPSCs) was investigated by the important bone markers. 3-[4, 5-dimethylthiazol-2-yl]-2, 5 diphenyl tetrazolium bromide (MTT) and scanning electron microscopy results confirmed the biocompatibility of the fabricated nanofibers, while higher proliferation rate of iPSCs was detected in PCL-PLLA(poly-P) group compared with the PCL-PLLA and tissue culture plate groups. Alkaline phosphatase activity, calcium content, and gene expression results demonstrated that osteogenic differentiation of iPSCs was increased when cultured on PCL-PLLA(poly-P) in comparison with other groups. According to the results, PCL-PLLA(poly-P) could be considered as a promising candidate for use as bone implants.

Improved chondrogenic response of mesenchymal stem cells to a polyethersulfone/polyaniline blended nanofibrous scaffold.

Owing to the fact that the cartilage tissue is not able to repair itself, the treatment of the joint damages is very difficult by current methods. Induction of tissue repair requires suitable cell and extracellular matrix. Providing these two parts can only be done using tissue engineering. In the present study, polyethersulfone (PES) and polyaniline (PANI) blend was electrospined for nanofibrous scaffold fabrication. Mesenchymal stem cells were isolated from human adipose tissue (AT-MSCs), and after characterization cultured on the PES-PANI scaffold and culture plate. Electron microscopic and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) colorimetric assays were used for biocompatibility evaluation of the scaffold and the chondrogenic differentiation potential of AT-MSCs were investigated by staining of proteoglycans and gene and protein expression evaluation. Alcian blue staining, real-time reverse-transcriptase polymerase chain reaction and Western blot results showed that chondrogenic differentiation potential of AT-MSCs was significantly increased when grown on PES-PANI nanofibers and was compared to the one grown on a culture plate. According to the results, PES-PANI has a promising potential to be used as a biomedical implant in patients with joints lesion, such as arthritis and osteoarthritis.

Decellularized Wharton's jelly extracellular matrix as a promising scaffold for promoting hepatic differentiation of human induced pluripotent stem cells.

Liver tissue engineering as a therapeutic option for restoring of damaged liver function has a special focus on using native decellularized liver matrix, but there are limitations such as the shortage of liver donor. Therefore, an appropriate alternative scaffold is needed to circumvent the donor shortage. This study was designed to evaluate hepatic differentiation of human induced pluripotent stem cells (hiPSCs) in decellularized Wharton's jelly (WJ) matrix as an alternative for native liver matrix. WJ matrices were treated with a series of detergents for decellularization. Then hiPSCs were seeded into decellularized WJ scaffold (DWJS) for hepatic differentiation by a defined induction protocol. The DNA quantitative assay and histological evaluation showed that cellular and nuclear materials were efficiently removed and the composition of extracellular matrix was maintained. In DWJS, hiPSCs-derived hepatocyte-like cells (hiPSCs-Heps) efficiently entered into the differentiation phase (G1) and gradually took a polygonal shape, a typical shape of hepatocytes. The expression of hepatic-associated genes (albumin, TAT, Cytokeratin19, and Cyp7A1), albumin and urea secretion in hiPSCs-Heps cultured into DWJS was significantly higher than those cultured in the culture plates (2D). Altogether, our results suggest that DWJS could provide a proper microenvironment that efficiently promotes hepatic differentiation of hiPSCs.

Chelating and Bridging Roles of 2-(2-Pyridyl)benzimidazole and Bis(diphenylphosphino)acetylene in Stabilizing a Cyclic Tetranuclear Platinum(II) Complex.

The reaction of complex [Pt(Me)(DMSO)(pbz)], 1, (pbz = 2-(2-pyridyl)benzimidazolate) with [PtMe(Cl)(DMSO)2], B, followed by addition of bis(diphenylphosphino)acetylene (dppac), gave the novel tetranuclear platinum complex [Pt4Me4(µ-dppac)2(pbz)2Cl2], 2, bearing both the pbz and dppac ligands. In this structure, the pbz ligands are both chelating and bridging to stabilize the tetraplatinum framework. The tetranuclear Pt(II) complex was fully characterized by NMR spectroscopy, X-ray crystallography, and mass spectrometry, and its electronic structure was investigated and supported by DFT calculations.

The anti-cancer effect of amygdalin on human cancer cell lines.

Derived from rosaceous plant seed, amygdalin belongs to aromatic cyanogenic glycoside group, and its anticancer effects have been supported by mounting evidence. In this study, we objected to investigate amygdalin effect on two antiapoptotic genes (Survivin, XIAP) and two lncRNAs (GAS5, MALAT1) in human cancer cells (A549, MCF7, AGS). Employing RT-qPCR analysis, we compared the mRNA levels of the genes related to apoptosis in A549, MCF7, and AGS cancer cells between amygdalin-treated (24, 48 and 72 h) and un-treated groups. RNA was extracted from both cell groups and then cDNAs were synthesized. The changes in the gene expression levels were specified using ΔΔCt method. RT-qPCR analysis has revealed that the expression of Survivin, XIAP, GAS5 and MALAT1 in amygdala-treated cancer cells were significantly different, compared to the un-treated cells. However, these expressions were different depending on the treatment time. According to the results, amygdalin significantly inhibited the expression level of Survivin, and XIAP genes in treated via untreated group. Our findings suggest that amygdalin might have an anticancer effect due to the various gene expressions in A549, MCF7, and AGS human cancer cells, showing it's potential as a natural therapeutic anticancer drug.