Analyzing the Factors Affecting Neonatal Mortality Control in Iran by Providing a Model.

INTRODUCTION: Despite Iran's success in reducing neonatal mortality rate, it is still far behind some developing countries and some Asian countries. The aim of this study was to summarize the measures taken and proposed solutions to design a model to control neonatal mortality. METHODS: This applied cross-sectional analytical study was performed using a factor analysis method derived from 4 models of neonatal mortality reduction. After reviewing different texts and patterns, the common and non-common dimensions of these patterns were set in a comparative table. The results of the comparative studies were designed in the form of a questionnaire and sent to 30 experts for reliability and validity. CVI and CVR validity and Cronbach's α reliability were confirmed and in order to validate the model, the final questionnaire was completed and summarized by interviewing 311 people from 7 provinces in a multi-stage interview method using multi-stage random sampling. Data analysis was performed using SPSS25 and AMOS-18 software. RESULTS: 6 factors were found to be effective in controlling neonatal mortality, including access to health care, health policy, health services, health information systems, family involvement, and evaluation. Access to health care services had the most significant effect with 23.19% of explained variance, and participation and evaluation with 1.19% of explained variance had the least effect. CONCLUSION: The proposed model has the greatest impact on the access to health care services and the least impact on the evaluation component.

Determinants of gold nanoparticle interactions with Proteins: Off-Target effect study.

Photothermal therapy is one of the promising approaches toward cancer treatment. To date, several compounds have been developed for this application, among which nanoparticles are attracting ever-increasing attention. One of the obstacles in developing efficient photothermal nanoparticle agents is their off-target effect which is mainly mediated via non-specific interactions with proteins. Such interaction not only reduces the bioavailability of the agent but also will cause protein aggregation that can be lethal. So, gaining knowledge on the mechanisms mediating such interactions will facilitate development of more effective agents. Our last studies showed the mechanism of action of two modified gold nanoparticles, folic acid functionalized gold nanoparticles (FA-AuNPs) and gold shelled Fe3O4 nanoparticles (AuFeNPs), as photothermal agents. In the current work, we focus on the interaction of these two NPs with human serum albumin (HSA) and human hemoglobin (Hb) as model proteins. The complex formation between NPs and proteins was investigated by fluorescence spectroscopy, dynamic light scattering and circular dichroism. Our data distinguishes the very distinct mode of interaction of charged and neutral NPs with proteins. While the interaction of neutral AuFeNP to proteins is protein dependent, charged nanoparticles FA-AuNP interact indistinguishably with all proteins via electrostatic interactions. Moreover, complexes obtained from FA-AuNPs with proteins are more stable than that of AuFeNP. However, the secondary structure content of proteins in the presence of NPs indicates the insignificant effect of NPs on the secondary structure of these proteins. Our data propose that the charge functionalization of the NPs is an effective way for modulating the interaction of nanoparticles with proteins.

Develop the World Health Organization Assessment Instrument for Mental Health System (WHO-AIMS) In IRAN / Desarrollar el instrumento de evaluación de la Organización Mundial de la Salud para el sistema de salud mental (WHO-AIMS) en IRÁN

Introduction: The tool for assessing the Mental Health System of the World Health Organization has been used in different countries in different countries,by which examining the mental health system and identifying their problems along with finding out the instrumental problems are done simoltaneously. Objetive: this study was conducted in order to develop the means of evaluating the mental health system organization of the world health organization in iran. Method: This research is based on the implementation, analytical, and in terms of variables, combination (qualitative and quantitative), and purposeful, exploratory, and from the perspective of the result, an application that was carried out in six phases. Phase I: Review of texts that have been used to recognize the status of countries Different and Iran. Phase II: The status of mental health system in Khuzestan province was investigated and the problems of mental health system and instrumental problems were determined. Phase III: weaknesses and strengths of the mental health system evaluation tool were surveyed in Khuzestan province, Phase IV: To identify the key components of the WHO Mental Health Routing Program and the 2013-2015 operational plan for development of tools, in the fifth phase: The proposed components were embedded in each main field of the tool, and the content of the content validity and content validity index were evaluated by the experts. Result: Finally, 11 main components were identified and 95 questions were designed for them, which in the sixth phase these questions Mental Health Managers were given an exploratory and confirmatory factor analysis and identified their main factors and their impact on the development of the Mental Health Assessment System of the World Health Organization. Using PLS software from 11 components and 95 suggested questions, 6 factors influencing The development of tools has been identified whose impact coefficients include: Leadership and Governance (0.972), mental health and e-service use (0.929), Policy and Legislative Framework (0.697), status analysis (0.613), mental health services pattern for common disorders (0.413), mental health promotion services (0.259). Conclusion: The development of the Mental Health Assessment Tool of the World Health Organization in Iran will help identify the mental health gap and, with regard to the problems, will be the best pattern for providing mental health services

Introducción: La herramienta para evaluar el Sistema de Salud Mental de la Organización Mundial de la Salud se ha utilizado en diferentes países en diferentes países, mediante el cual el examen del sistema de salud mental y la identificación de sus problemas junto con el descubrimiento de los problemas instrumentales se realizan de forma simultánea. Objetive: este estudio se realizó con el fin de desarrollar los medios para evaluar la organización del sistema de salud mental de la organización mundial de la salud en Irán. Método: Esta investigación se basa en la implementación, analítica y en términos de variables, combinación (cualitativa y cuantitativa), y con una finalidad, exploratoria y, desde la perspectiva del resultado, una aplicación que se realizó en seis fases. Fase I: Revisión de textos que se han utilizado parareconocer el estado de países diferentes e Irán. Fase II: Se investigó el estado del sistema de salud mental en la provincia de Khuzestan y se determinaron los problemas del sistema de salud mental y los problemas instrumentales. Fase III: se examinaron las debilidades y fortalezas de la herramienta de evaluación del sistema de salud mental en la provincia de Khuzestan, Fase IV: para identificar los componentes clave del Programa de Enrutamiento de Salud Mental de la OMS y el plan operativo 2013-2015 para el desarrollo de herramientas, en la quinta fase : Los componentes propuestos se integraron en cada campo principal de la herramienta, y los expertos evaluaron el contenido de la validez de contenido y el índice de validez de contenido. Resultado: Finalmente, se identificaron 11 componentes principales y se diseñaron 95 preguntas para ellos, que en la sexta fase a estas Gerentes de Salud Mental se les realizó un análisis factorial exploratorio y confirmatorio e identificaron sus factores principales y su impacto en el desarrollo de la Salud Mental Sistema de evaluación de la Organización Mundial de la Salud. Utilizando el software PLS de 11 componentes y 95 preguntas sugeridas, se han identificado 6 factores que influyen El desarrollo de herramientas cuyos coeficientes de impacto incluyen: Liderazgo y Gobernanza (0,972), salud mental y uso de servicios electrónicos (0,929), Marco Político y Legislativo (0.697), análisis de estado (0.613), patrón de servicios de salud mental para trastornos comunes (0,413), servicios de promoción de salud mental (0,259). Conclusión: El desarrollo de la Herramienta de evaluación de salud mental de la Organización Mundial de la Salud en Irán ayudará a identificar la brecha de salud mental y, con respecto a los problemas, será el mejor patrón para proporcionar servicios de salud mental.

Gold nanoparticles promote a multimodal synergistic cancer therapy strategy by co-delivery of thermo-chemo-radio therapy.

Multimodal cancer therapy has become a new trend in clinical oncology due to potential generation of synergistic therapeutic effects. Herein, we propose a multifunctional nanoplatform comprising alginate hydrogel co-loaded with cisplatin and gold nanoparticles (abbreviated as ACA) for triple combination of photothermal therapy, chemotherapy and radiotherapy (thermo-chemo-radio therapy). The therapeutic potential of ACA was assessed in combination with 532 nm laser and 6 MV X-ray against KB human mouth epidermal carcinoma cells. The results demonstrated that tri-modal thermo-chemo-radio therapy using ACA induced a superior anticancer efficacy than mono- or bi-modality treatments. The intracellular reactive oxygen species (ROS) level in KB cells treated with tri-modal therapy was increased by 4.4-fold compared to untreated cells. The gene expression analysis demonstrated the up-regulation of Bax pro-apoptotic factor (by 4.5-fold) and the down-regulation of Bcl-2 anti-apoptotic factor (by 0.3-fold). The massive cell injury and the appearance of morphological characteristics of apoptosis were also evident in the micrograph of KB cells caused by thermo-chemo-radio therapy. Therefore, ACA nanocomplex can be offered as a promising platform to combine photothermal therapy, chemotherapy and radiotherapy, thereby affording an opportunity for combating chemo- and radio-resistant tumors.

Conductive hydrogels based on agarose/alginate/chitosan for neural disorder therapy.

Electroactive scaffolds derived from carbohydrate hydrogels were synthesized, resulting in a large shift in the conductivity of chitosan (CS) from 10-6 S/cm to about 10-3 S/cm, assigned to CS-oligoaniline. Several analyses including UV-vis spectroscopy and cyclic voltammetry were performed, before examining the carbohydrate-based scaffolds for their ability to recapitulate the neural tissue microenvironment. Good conductivity and resemblance of the modulus to soft tissue of the optimized hydrogels led to appropriate cellular activity and neural regeneration. The loss of dopaminergic neurons as the prominent source of dopamine in the central nervous system results in the deterioration of multiple brain functions such as voluntary movement and behavioral processes. To overcome this, olfactory ecto-mesenchymal stem cells (OE-MSCs) were induced to differentiate into dopaminergic neuron-like cells on hydrogels through a monolayer arrangement cell culture by using cocktail neurotrophic factors including sonic hedgehog (SHH), fibroblast growth factor 8 (FGF8), basic fibroblast growth factor (bFGF), glial cell line-derived neurotrophic factor (GDNF) and brain derived neurotrophic factor (BDNF). The differentiation capacity of a series of OE-MSCs on the conductive hydrogel was evaluated by real-time PCR, immunocytochemistry and flow cytometry, and the expression of tyrosine hydroxylase (TH) and dopamine transporter (DAT) neural and dopaminergic markers. The results of this study represent the first steps in designing and implementing advanced platforms based on conductive polysaccharide hydrogels for neural disorder therapies, such as the treatment of Parkinson's disease.

Conductive hydrogel based on chitosan-aniline pentamer/gelatin/agarose significantly promoted motor neuron-like cells differentiation of human olfactory ecto-mesenchymal stem cells.

Developing a simple produces for efficient derivation of motor neurons (MNs) is essential for neural tissue engineering studies. Stem cells with high capacity for neural differentiation and scaffolds with the potential to promote motor neurons differentiation are promising candidates for neural tissue engineering. Recently, human olfactory ecto-mesenchymal stem cells (OE-MSCs), which are isolated easily from the olfactory mucosa, are considered a new hope for neuronal replacement due to their neural crest origin. Herein, we synthesized conducting hydrogels using different concentration of chitosan-g-aniline pentamer, gelatin, and agarose. The chemical structures, swelling and deswelling ratio, ionic conductivity and thermal properties of the hydrogel were characterized. Scaffolds with 10% chitosan-g-aniline pentamer/gelatin (S10) were chosen for further investigation and the potential of OE-MSCs as a new source for programming to motor neuron-like cells investigated on tissue culture plate (TCP) and conductive hydrogels. Cell differentiation was evaluated at the level of mRNA and protein synthesis and indicated that conductive hydrogels significantly increased the markers related to motor neurons including Hb-9, Islet-1 and ChAT compared to TCP. Taken together, the results suggest that OE-MSCs would be successfully differentiated into motor neuron-like cells on conductive hydrogels and would have a promising potential for treating motor neuron-related diseases.

Microtubule network as a potential candidate for targeting by gold nanoparticle-assisted photothermal therapy.

Photothermal therapy is achieving ever-increasing attention as a promising method for killing cancer cells. Although, gold nanoparticles are regarded as one of the most effective photothermal therapy agents, the mechanisms underlying their action have to be addressed. Moreover, studies have showed that gold nanoparticles induce apoptosis in treated cultures. Hence, in this study, we investigated the interaction of folic acid functionalized gold nanoparticles and gold-shelled Fe3O4 nanoparticles with microtubule and microtubule associated protein tau in order to introduce intracellular targets of these nanoparticles and provide a holistic view about the mechanism of action of gold nanoparticles used in photothermal therapy. Various spectroscopic methods were used to find gold nanoparticles interaction with Tubulin and Tau. Our results indicated that these gold nanoparticles interact with both Tau and Tubulin and their affinity increases as temperature rises. Also, the results illustrated that quenching mechanism for gold nanoparticles interaction with Tubulin and Tau was static. The hydrophobic interaction was determined as driving force for gold nanoparticles binding to Tubulin and Tau. Moreover, it was showed that both type of gold nanoparticles stabilize microtubule polymers. These results suggest Tau and Tubulin as intracellular target of gold nanoparticles and propose that microtubule network is at the heart of apoptosis mechanisms initiated by photothermal therapy.

Alginate/chitosan hydrogel containing olfactory ectomesenchymal stem cells for sciatic nerve tissue engineering.

Regeneration and functional recovery after peripheral nerve damage still remain a significant clinical problem. In this study, alginate/chitosan (alg/chit) hydrogel was used for the transplantation of olfactory ectomesenchymal stem cells (OE-MSCs) to promote peripheral nerve regeneration. The OE-MSCs were isolated from olfactory mucosa biopsies and evaluated by different cell surface markers and differentiation capacity. After creating sciatic nerve injury in a rat model, OE-MSCs were transplanted to the injured area with alg/chit hydrogel which was prepared and well-characterized. The prepared hydrogel had the porosity of 91.3 ± 1.27%, the swelling ratio of 379% after 240 min, weight loss percentages of 80 ± 5.56% after 14 days, and good blood compatibility. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, 4',6-diamidino-2-phenylindole, and LIVE/DEAD staining were done to assay the behavior of OE-MSCs on alg/chit hydrogel and the results confirmed that the hydrogel can provide a suitable substrate for cell survival. For functional analysis, alg/chit hydrogel with and without OE- MSCs was injected into a 3-mm sciatic nerve defect of Wistar rats. The results of the sciatic functional index, hot plate latency, electrophysiological assessment, weight-loss percentage of wet gastrocnemius muscle, and histopathological examination using hematoxylin-eosin and Luxol fast blue staining showed that utilizing alg/chit hydrogel with OE-MSCs to the sciatic nerve defect enhance regeneration compared to the control group and hydrogel without cells.

Differentiation of human mesenchymal stem cells (MSC) to dopaminergic neurons: A comparison between Wharton's Jelly and olfactory mucosa as sources of MSCs.

The generation of dopaminergic neurons from stem cells is a potential therapeutic approach to treat neurodegenerative disorders, such as Parkinson's disease. The current study aims to investigate the potential of two different types of mesenchymal stem cells derived from human Wharton's jelly and nasal cavity for differentiation into dopaminergic neurons. The differentiation capacities of both cell types were evaluated using real-time PCR, immunocytochemistry, flow cytometry and HPLC. Wharton's jelly-derived mesenchymal stem cells (WJ-MSCs) are noted for their capability to differentiate into mesodermal and non-mesodermal cells, including neurons. However, it was demonstrated that having the same neuroectodermal origin as the nervous system, the olfactory ectomesenchymal stem cells (OE-MSCs) expressed the neural marker MAP2 as well as dopaminergic markers such as tyrosine hydroxylase (TH), dopamine transporter (DAT) and PITX3 to a greater extent than the WJ-MSCs both at the level of mRNA and protein. Furthermore, quantitative flow cytometric evaluation of these markers at 12 days post-induction supported the above-mentioned results. Finally, the assessment of the functionality of differentiated cells and their ability to synthesize dopamine measured by HPLC revealed that the OE-MSC-derived dopaminergic cells released almost the same amount of dopamine as that secreted by WJ-MSC-derived cells. Thus it showed the difference in their functionality to be negligible. Overall, it may be concluded that higher proliferation and differentiation capacity of OE-MSCs, along with their easier harvestability and autologous transplantability compared with WJ-MSCs, makes them a better cell source for stem cell therapy of neurodegenerative disorders which are caused by degeneration of dopaminergic neurons.

Biological evaluations of newly-designed Pt(II) and Pd(II) complexes using spectroscopic and molecular docking approaches.

To perform biological evaluations of newly-designed Pt(II) and Pd(II) complexes, the present study was conducted with targeted protein human serum albumin (HSA) and HCT116 cell line as model of human colorectal carcinoma. The binding of Pt(II) and Pd(II) complexes to HSA was analyzed using fluorescence spectroscopy and molecular docking. The thermal stability and alterations in the secondary structure of HSA in the presence of Pt(II) and Pd(II) complexes were investigated using the thermal denaturation method and circular dichroism (CD) spectroscopy. The cytotoxicity of the Pt(II) and Pd(II) complexes was studied against the HCT116 cell line using MTT assay. The binding analysis revealed that the fluorescence findings were well in agreement with docking results such that there is only one binding site for each complex on HSA. Binding constants of 8.7 × 103 M-1, 2.65 × 103 M-1, 0.3 × 103 M-1, and 4.4 × 103 M-1 were determined for Pd(II) and Pt(II) complexes (I-IV) at temperature of 25 °C, respectively. Also, binding constants of 1.9 × 103 M-1, 15.17 × 103 M-1, 1.9 × 103 M-1, and 13.1 × 103 M-1 were determined for Pd(II) and Pt(II) complexes (I-IV) at temperature of 37 °C, respectively. The results of CD and thermal denaturation showed that the molecular structure of HSA affected by interaction with Pt(II) and Pd(II) complexes is stable. Cytotoxicity studies represented the growth suppression effect of the Pt(II) and Pd(II) complexes toward the human colorectal carcinoma cell line. Therefore, the results suggest that the new designed Pt(II) and Pd(II) complexes are well promising candidates for use in cancer treatment, particularly for human colorectal cancer. Communicated by Ramaswamy H. Sarma.

Human olfactory stem cells: As a promising source of dopaminergic neuron-like cells for treatment of Parkinson's disease.

The production of dopaminergic (DA) neurons from stem cells holds a great promise for future clinical treatment of neurodegenerative diseases, such as Parkinson's disease (PD). Olfactory ecto-mesenchymal stem cells (OE-MSCs) derived from the adult human olfactory mucosa can be easily isolated and expanded in culture while maintaining their immense plasticity. In addition to reduced ethical concerns, OE-MSCs could be transplanted across allogeneic barriers, making them desirable stem cells for clinical applications. The goal of this study was to define the potentiality of human olfactory mucosa-derived MSCs aimed at differentiation into DA neuron-like cells. OE-MSCs were induced to differentiate to DA neuron-like cells in vitro by using sonic hedgehog (SHH), fibroblast growth factor 8 (FGF8), basic fibroblast growth factor (bFGF), Glial cell line-derived neurotrophic factor (GDNF) and brain derived neurotrophic factor (BDNF). Then the differentiated neurons were characterized for expression of DA neuron markers by Real-time PCR, immunocytochemistry and flow cytometry. Our findings showed that differentiated OE-MSCs could significantly express DA neuron markers at mRNA and protein levels along with dopamine release 12 days post-differentiation. These results support the viability and feasibility of using OE-MSCs as a source of in vitro generated DA neuron-like cells for treatment of DA disorders namely PD.

Multimodal cancer cell therapy using Au@Fe2O3 core-shell nanoparticles in combination with photo-thermo-radiotherapy.

In this study, gold coated iron oxide nanoparticle (Au@Fe2O3 NP) was synthesized in a core-shell structure. Photothermal and radiosensitization effects of Au@Fe2O3 NPs were investigated on KB human mouth epidermal carcinoma cell line. Cell death and apoptosis were measured to study the effects of nanoparticles in combination with both radiotherapy (RT) and photothermal therapy (PTT). The KB cells were treated with Au@Fe2O3 NPs (20 µg/ml; 4 h) and then received different treatment regimens of PTT and/or RT using laser (808 nm, 6 W/cm2, 10 min) and/or 6 MV X-ray (single dose of 2 Gy). Following the various treatments, MTT assay was performed to evaluate the cell survival rate. Also, the mode of cell death was determined by flow cytometry using an annexinV-fluorescein isothiocyanate/propidium iodide apoptosis detection kit. No significant cell death was observed due to laser irradiation. The viability of the cells firstly incubated with NPs and then exposed to the laser was significantly decreased. Additionally, our results demonstrated that Au@Fe2O3 NP is a good radiosensitizer at megavoltage energies of X-ray. When nanoparticles loaded KB cells were received both laser and X-ray, the cell viability substantially decreased. Following such a combinatorial treatment, flow cytometry determined that the majority of cell death relates to apoptosis. In conclusion, Au@Fe2O3 NP has a great potential to be applied as a photo-thermo-radiotherapy sensitizer for treatment of head and neck tumors.

Differentiation of neural crest stem cells from nasal mucosa into motor neuron-like cells.

Cell transplantation is a potential therapeutic approach for repairing neuropathological and neurodegenerative disorders of central nervous system by replacing the degenerated cells with new ones. Among a variety of stem cell candidates to provide these new cells, olfactory ectomesenchymal stem cells (OE-MSCs) have attracted a great attention due to their neural crest origin, easy harvest, high proliferation, and autologous transplantation. Since there is no report on differentiation potential of these cells into motor neuron-like cells, we evaluated this potential using Real-time PCR, flowcytometry and immunocytochemistry after the treatment with differentiation cocktail containing retinoic acid and Sonic Hedgehog. Immunocytochemistry staining of the isolated OE-MSCs demonstrated their capability to express nestin and vimentin, as the two markers of primitive neuroectoderm. The motor neuron differentiation of OE-MSCs resulted in changing their morphology into bipolar cells with high expression of motor neuron markers of ChAT, Hb-9 and Islet-1 at the level of mRNA and protein. Consequently, we believe that the OE-MSCs have great potential to differentiate into motor neuron-like cells and can be an ideal stem cell source for the treatment of motor neuron-related disorders of central nervous system.

Selective apoptosis induction in cancer cells using folate-conjugated gold nanoparticles and controlling the laser irradiation conditions.

In this study, we explained in detail a targeted nano-photo-thermal therapy (NPTT) method to induce selective apoptosis in cancer cells. Folate-conjugated gold nanoparticles (F-AuNPs) were synthesized by tailoring the surface of AuNPs with folic acid to enhance the specificity of NPTT. KB cancer cells, as a folate receptor over-expressing cell line, and L929 normal cells with low level of folate receptors were incubated with the synthesized F-AuNPs and then irradiated with various laser intensities and exposure durations. Following various regimes of NPTT, we assessed the level of cell viability and the ratio of apoptosis/necrosis. No significant cytotoxicity was observed for both cell lines at concentrations up to 40 µM of F-AuNPs. Moreover, no significant cell lethality occurred for various laser irradiation conditions. The viability of KB and L929 cells incubated with F-AuNPs (40 µM; 6 h) and then irradiated by laser (1 W/cm2; 2 min) was 57 and 83%, respectively. It was also demonstrated that the majority of cancer cell death is related to apoptosis (41% apoptosis of 43% overall cell death). In this process of F-AuNPs based NPTT, it may be concluded that the main factor determining whether a cell dies due to apoptosis or necrosis depends on laser irradiation conditions. In this study, we explained in detail a targeted nano-photo-thermal therapy (NPTT) method to induce selective apoptosis in cancer cells.