Design, Development and Evaluation of Dual Drug Nanomedicine for Non-Small Cell Lung Cancer

Resistance to conventional chemotherapy is a big challenge in the treatment of cancer including non-small cell lung cancer (NSCLC). A combination of natural chemo sensitizer agents with chemotherapy offers unique advantages over monotherapy alone. However, free unbound drugs, (in combination or as a single agent), lack tumor-targeted accumulation and therefore can be easily eliminated from the patient body. Moreover, some drugs are hydrophobic, and their organic solvents cause in vivo toxicity, thereby limiting their capability in clinical translation. Herein, dual loaded biocompatible and biodegradable nanoparticles (NPs) using Gemcitabine (Gem)a pyrimidine nucleoside antimetabolite and Gambogic acid (GA) (a highly hydrophobic chemo sensitizer agent)- were developed on human serum albumin-tannic acid nano-platform (HTA) for targeted treatment of NSCLC.Our in vitro results demonstrate that Gem and GA combination therapy has tremendous potential due to their high efficacy on NSCLC, and GA sensitize NSCLC to Gem therapy. However, GA used in combination with Gem suffers from limited solubility which subsequently leads to a decline in therapeutic efficacy. Therefore, in order to overcome this, in the present study GA and Gem were encapsulated in human serum albumin-tannic acid nanoparticles by the solvent evaporation method. In this platform, HTA is a biocompatible nanocarrier that binds to both GA and Gem. Physico chemical characterizations studies revealed that GA and Gem are successfully encapsulated in HTA NPs with uniform spherical morphology. These nanoparticles were readily taken up by NSCLC cells (A549 and H1299) in a concentration and time-dependent manner. Apart from an increase in GA solubility, encapsulated GA and Gem subsequently manifested elevated therapeutic efficacy, which was confirmed by cell viability, colony formation, migration and invasion studies. Furthermore, in vivo and ex vivo imaging analysis demonstrated notable tumor-targeting behavior of our uniquely designed HTA NPs in mice bearing A549 xenograft tumors. These findings clearly illustrate that our dual loaded NPs can be efficiently utilized to improve cancer therapy and tumor eradication

Seasonal variation of Guillain-Barré syndrome in Iranian patients: a retrospective study

Background: It seems that the incidence of Guillain-Barré syndrome (GBS) has seasonal trends depending on weather as well as environmental and demographic factors such as upper respiratory tract infection (URI). The aim of this study was to evaluate seasonality of GBS and its electrophysiological subtypes. Methods: In this cross-sectional study, the records of all admitted patients to all wards of Dr. Shariati Hospital from March 2009 to March 2019 according to ICD-10 codes for GBS and other similar neuropathies were investigated and 87 patients were registered based on fulfillment of Brighton criteria and symptom onset during the recent 4 weeks. Statistical analysis was performed by IBM SPSS version 20. A p-value < 0.05 was considered statistically significant. Results: Most of the patients (63.2%, n=55) were men. The mean age of them was 49.1±19.2 years, and 41.3% (n=36) and 10.3% (n=9) participants had recent URI and gastrointestinal infection, respectively. The frequency of GBS in different seasons was 35.6% (n=31) patients in the winter, 27.6% (n=24) in the autumn, 19.6% (n=17) in the spring, and 17.2% (n=15) in the summer. The most frequent electrophysiological subtype was acute inflammatory demyelinating polyneuropathy (AIDP) in all seasons. The most common GBS disability score was 1. Conclusion: The highest and the lowest occurrence was seen in the winter and summer, respectively. AIDP was the most common electrophysiological subtype in all seasons. More studies are suggested to evaluate other aspects of GBS on more details

Ethnobotanical study of medicinal plants of Boyer Ahmad and Dena regions in Kohgiluyeh and Boyer Ahmad province, Iran

Background and aims: The current paper aimed to collect and document the information about medicinal plants of Boyer Ahmad and Dena regions and their applications by indigenous inhabitants. Methods: The field surveys were carried out from March 2015 to September 2016 under supervision of local people. Collected plant specimens were identified to species level using Flora of Iran and Flora Iranica. Subsequently, information including scientific names, local names, parts used, method of preparation, medicinal effects, growth forms, and chorotypes for 71 species were recorded. Results: Medicinal plants belonged to 62 genera and 29 families. Apiaceae (14.08%) and Lamiaceae (14.08%) had the most number of species among other families. Based on Raunkier method, hemicryptophytes with 42.25% is the highest growth form and the most common chorotype was Irano-Turanian type (70.42%). The most used parts are aerial parts (40/85%),‎ and the most common mode of preparation was infusion (24%). The results of this study indicate that local people in Boyer Ahmad and Dena regions have used all collected plants for medicinal, food and sanitary purposes and their knowledge about identification of plants and their habitats, medicinal and edible properties is extensive. Conclusions: Native knowledge leads to obtaining valuable information including medicinal properties of plants, usable parts, time of growth, best time for harvesting and areas which have growing potential. Therefore, it is vital to investigate the native knowledge about medicinal plants in various regions of Iran

Investigating activity of masticatory muscles in patients with hypermobile temporomandibular joints by using EMG

Background: Temporomandibular joint hypermobility (TMJH) can manifest higher range of motions in mandible. The aim of this study was to investigate and compare the activity of masticatory muscle of TMJs in healthy individuals and patients with mild, moderate and severe TMJH. Material and Methods: In this clinical study, 69 patients (between the ages of 22 to 42) with manifestation of TMJH were included. The patients were divided into three groups based on their maximum mouth opening (MMO): (light) with MMO of 50-55 mm; (moderate) with MMO between 55 to 65 mm; and (severe) with MMO >65 mm. Also, 20 healthy people with profiled tomography in the last 6 months were invited as control group (healthy) with normal MMO (<50 mm). All the groups subjected to electromyogram (EMG) in 2 steps: maximal voluntary clenching (MVC) of the jaws; and during chewing of bread by using one side of the jaws voluntary. The collected data were analyzed by Student T-test and Chi-Square tests using SPSS software version 15 at significant level of 0.05. Results: Both TMJs of light, moderate and severe groups showed significant differences in frequency, time of activity and rest in comparison with healthy group during chewing and MVC (all p values < 0.01). Conclusions: Masticatory muscles activity reduced in relation with the severity of TMJH and higher excessive mouth opening

The Effectiveness of Choice Theory Education on Reducing Work-Family Conflict of Women

Background: One of the most significant issues of areas of work and family interactions is work-family conflict. Dominant traditional and stereotypical attitudes toward women’s roles and doing institutionalized house chores provoke problems such as a decline in organizational performance and adverse physical, mental, and behavioral effects in women. The purpose of this study was to explore the effectiveness of choice theory education on reducing work-family conflict of women working in the hospital. Methods: The quasi-experimental research conducted in a pre-test and post-test control group design aimed to examine the effectiveness of the choice theory education on reducing work-family conflict of 12 participants in the experimental group and 12 participants in the control group who were selected by multistage cluster sampling. &nbsp; Results: The result of Covariance analysis revealed that there was a significant difference between the experimental and control group in post-test (Pvalue&lt; 0.001, F=50.13). Conclusions: &nbsp;It can be concluded that the education of choice theory's concepts can be used as one of the strategies of reducing the work-family conflict to confront its negative consequences in organizations and families

Gambogic acid: A shining natural compound to nanomedicine for cancer therapeutics

The United State Food and Drug Administration has permitted number of therapeutic agents for cancer treatment. Most of them are expensive and have some degree of systemic toxicity which makes overbearing in clinical settings. Although advanced research continuously applied in cancer therapeutics, but drug resistance, metastasis, and recurrence remain unanswerable These accounts to an urgent clinical need to discover natural compounds with precisely safe and highly efficient for the cancer prevention and cancer therapy. Gambogic acid (GA) is the principle bioactive and caged xanthone component, a brownish gamboge resin secreted from the of Garcinia hanburyi tree. This molecule showed a spectrum of biological and clinical benefits against various cancers. In this review, we document distinct biological characteristics of GA as a novel anti-cancer agent. This review also delineates specific molecular mechanism(s) of GA that are involved in anti-cancer, anti-metastasis, anti-angiogenesis, and chemo-/radiation sensitizer activities. Furthermore, recent evidence, development, and implementation of various nanoformulations of gambogic acid (nanomedicine) have been described

Cell-free seminal mRNA of DDX4 and TNP1 Genes as Potential Biomarkers of the Presence of Sperm in the Testicular Tissue

Introduction: Non-obstructive azoospermia (NOA) is one of the reasons for infertility in men, and different factors including genetic factors are involved in its development. Since taking biopsies of the testicular tissue for assisted reproductive technologies (ARTs) is invasive and time-consuming, and the testicular tissue is heterogeneous, introducing a biomarker for predicting the possibility of the presence of sperm in the testicle can increase the ART efficiency. Accordingly, Cell-free seminal mRNA (CFs-mRNA), which is found in many fluids of the body including the seminal fluid of NOA individuals, can be employed as a biomarker for this purpose. Materials and methods: This study was conducted on 15 men suffering NOA, candidates for testicular sperm extraction (TESE), along with 15 healthy men as control. The testicular tissue of 10 patients was examined using hematoxylin and eosin staining and then classified according to Johnsen scoring. RNA was extracted from the cell-free plasma of semen samples and cDNA was synthesized. The Expression level of TNP1 and DDX4 genes was investigated using real-time polymerase chain reaction (PCR). Results: The expression of CFS-mRNA of the DDX4 gene was observed in only one sample of NOA individuals (10%), showing a score of 8. Further, the expression of CFS-mRNA of the TNP1 gene was observed only in two samples (20%) of NOA patients whose scores were 3 and 8. Conclusion: Insufficiency or lack of expression of CFS-mRNA of TNP1 and DDX4 genes may be helpful in predicting the absence of sperm in the testicular tissue of NOA patients in terms of sperm retrieval for ART. Yet, further studies with more specific and sensitive techniques are required to achieve a more solid and precise conclusion

The Effectiveness of Choice Theory Education on Reducing Work-Family Conflict of Women

Background: One of the most significant issues of areas of work and family interactions is work-family conflict. Dominant traditional and stereotypical attitudes toward women’s roles and doing institutionalized house chores provoke problems such as a decline in organizational performance and adverse physical, mental, and behavioral effects in women. The purpose of this study was to explore the effectiveness of choice theory education on reducing work-family conflict of women working in the hospital. Methods: The quasi-experimental research conducted in a pre-test and post-test control group design aimed to examine the effectiveness of the choice theory education on reducing work-family conflict of 12 participants in the experimental group and 12 participants in the control group who were selected by multistage cluster sampling. &nbsp; Results: The result of Covariance analysis revealed that there was a significant difference between the experimental and control group in post-test (Pvalue&lt; 0.001, F=50.13). Conclusions: &nbsp;It can be concluded that the education of choice theory's concepts can be used as one of the strategies of reducing the work-family conflict to confront its negative consequences in organizations and families

Investigating the Mediating Role of Distress Tolerance in the Relationship between Early Maladaptive Schemas and Psychiatric Symptoms among Addicts

Background: This study aimed to determine the mediating role of distress tolerance in the relationship between early maladaptive schemas and psychiatric symptoms among addicts. Methods: The statistical population of this study consists of addicts referring to addiction treatment clinics in Zanjan city, Iran. Using the multi-stage cluster sampling method, 150 participants were selected as a sample and completed the questionnaires. Early maladaptive schema questionnaire-short form, symptom checklist-25 (SCL-25), and the distress tolerance scale were completed by participants. Results: The findings of this study indicate a negative and significant relationship between early maladaptive schemas and distress tolerance among addicts. Also, there is a positive and significant relationship between early maladaptive schemas and psychiatric symptoms among addicts. It can be said that there is a significant negative relationship between distress tolerance and psychiatric symptoms in addicts. Conclusions: The final results of this study show that in the relationship between early maladaptive schemas and psychiatric symptoms among addicts in Zanjan city, distress tolerance plays a mediating role and the model has a goodness of fit. Keywords: Distress tolerance, Early maladaptive schemas, Psychiatric symptoms, Addicts

Investigating the Mediating Role of Distress Tolerance in the Relationship between Early Maladaptive Schemas and Psychiatric Symptoms among Addicts

Background: This study aimed to determine the mediating role of distress tolerance in the relationship between early maladaptive schemas and psychiatric symptoms among addicts. Methods: The statistical population of this study consists of addicts referring to addiction treatment clinics in Zanjan city, Iran. Using the multi-stage cluster sampling method, 150 participants were selected as a sample and completed the questionnaires. Early maladaptive schema questionnaire-short form, symptom checklist-25 (SCL-25), and the distress tolerance scale were completed by participants. Results: The findings of this study indicate a negative and significant relationship between early maladaptive schemas and distress tolerance among addicts. Also, there is a positive and significant relationship between early maladaptive schemas and psychiatric symptoms among addicts. It can be said that there is a significant negative relationship between distress tolerance and psychiatric symptoms in addicts. Conclusions: The final results of this study show that in the relationship between early maladaptive schemas and psychiatric symptoms among addicts in Zanjan city, distress tolerance plays a mediating role and the model has a goodness of fit. Keywords: Distress tolerance, Early maladaptive schemas, Psychiatric symptoms, Addicts