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Background: Fatigue is the most common complaint among patients with rheumatoid arthritis, leading to decreased productivity and reduced quality of life.Aim: The present study was conducted with aim to compare the effect of sole reflexology and stretching exercises on fatigue of rheumatoid arthritis patients.Method: This clinical trial study was conducted on patients with rheumatoid arthritis in Yasuj city of Iran during 2017-2018. Participants were selected through convenience sampling method but randomly allocated to one of the three groups using randomized block allocation. Multidimensional fatigue questionnaire was used to collect data at two times of pre and post interventions. The interventions were performed during 30 minutes per session for three sessions per week over one month.Results: Mean scores of global fatigue before the interventions in the sole reflexology group was 80.72±8.61, in stretching exercise group 81±7.30, and in control group (76.43±8.17), however, these values for post intervention were reported to be 68.72±8.59, 50.95±5.73, and 76.82±7.43, respectively. Intergroup comparison showed significant differences between the sole reflexology and stretching exercise groups with the control group (p

Introduction Language is a seemingly simple but at the same time very complex phenomenon. Linguists have always tried to understand what language is and provide a definition of it. Among the sages, Mulla Sadra has an ontological view of speech and, relying on his system of jurisprudence, defines language using the principles of the originality of existence, sequence of existence, and substantial motion. The purpose of this article is to provide a descriptive-analytical explanation of Mulla Sadra's view on language but from an angle that is in correspondence and similar to the universe. He introduces language in a system that corresponds perfectly to the universe and it means both with an ascending and descending course, beginning and end, grading and rank, fertility and dynamism, and in proportion and addition with the audience. Part of this correspondence is in the relationship between mind and object. He believes that language and existence are so intertwined that existence is nothing but words.Research Questions:Is language an existential truth or a contractual tool?What is the relationship between language and universe?What are the areas of similarity and correspondence between language and the universe? Literature Review Mohsen Pirhadi and Alilah Badashti, in the article “Criticism and review of verbal and emotional speech based on transcendental wisdom” compare the views of theologians and Mulla Sadra regarding the verbal or emotional nature of the speech, and its purpose is to investigate whether the divine word is verbal or emotional. However, the following article not only examines speech in divine and human dimensions, but its purpose is to study language in the system of existence.Maqsood Mahmoudi also examines the views of theologians and Mulla Sadra in the article “Explanation of the attribute of speech, the divine word and the descent of revelation based on the transcendental wisdom “similar to the previous article.Also, Seyyed Mohammad Hossein Mirdamadi and Seyyed Mehdi Emami Juma, in the article “Philosophical principles and principles of Kalam and Divine Book in the modern ontology of Mulla Sadra” deal with the issue of if we want to consider existence as the Word or Divine Book, what are the characteristics of existence we face. To explain this point of view, he points to thirteen rules for studying the Book of Being, which are necessary to know, such as the unlimitedness of the divine word, the unseenness of the divine word, etc. The purpose of this article is not only to know the divine word, but it considers the language regardless of whether it is divine or not, compared to the characteristics of the universe. Methodology The purpose of this article is to examine the similarities and correspondences between the world of existence and speech from Mulla Sadra's point of view, which is done with a comparative approach and descriptive-analytical method. This work has been done through library research and information gathering, and then comparing Mulla Sadra's views in the two areas of existence and speech. Conclusion Just as Mulla Sadra is the founder of a new ruling system regarding the world of existence, he also presents new and creative views on the nature of language, which are completely consistent with the world of existence and can only be understood by knowing his philosophical principles. He introduces words and speech in a structure that, firstly, has unity in connection with the composite mind and secondly, in similarity and correspondence with the universe, it starts from a specific beginning and leads to a specific destination, but this end itself becomes the beginning for Siri. An ascent that ends at the initial origin. This process of descent and ascent occurs in a two-way interaction between the speaker and the listener, and the role of both is important in this matter. Just as the world of existence is multilevel and this is a favor from the Holy Prophet to provide the way of knowledge for human beings, speech also corresponds to the world of existence, it is multilevel and every word leads us to a specific meaning with a specific level. Interaction with the audience makes sense. Existence is constantly giving birth and moving, and speech is a creative gift that invents new sentences and meanings at the foot of the generative existence. In the end, existence and speech are so similar that he considers the universe to be nothing but speech.

Undoubtedly, the conviction of a mystic's Spiritual Journeying is the result of a strong foundation of his epistemological Principles and assumptions. The findings of this study, which is based on library studies and with a descriptive-analytical method, examines the principles and assumptions of the Spiritual Journeying of the fifth-century Jewish mystic Baḥya Ben Joseph ibn Paḳūda. It shows that he based his Spiritual Journeying structure on the three pillars of reason, written sources and Jewish traditions. In this treatise, which is full of verses from the Bible, Baḥya pays special attention to the sayings of the Jewish predecessors and prioritizes reasoning over Jewish traditions and imitation, also believes that one who has intellectual ability should not be content with traditions. In Al-Hidāyah ilá farāʼīḍ al-qulūb one can find biblical beliefs that Bahya has hypothesized, including the Jewish people being chosen by God and the nations closest to him, and who believes that the destruction of the temple is the atonement for the great sins of the Jews. He considers the Jews to be living in a foreign land and asks God to allow the construction of the third temple.such beliefs, which are related to the spiritual aspect of a person, easily affect his intellectual and practical system.

Introduction: Cone-beam computed tomography is used for specialized imaging of dental and maxillofacial structures. CBCTs capabilities and facilities for dental and maxillofacial imaging have resulted in their increasing clinical use. Although the dose of CBCT tests is low, its widespread use increases the cumulative dose. This study was conducted to evaluate head and neck effective dose and image quality in different organs for various exposure techniques in CBCT imaging.Material and Methods: This study was performed on various CBCT imaging examinations. Head and neck parts of anthropomorphic male Rando® Alderson Phantom and thermoluminescent dosimeters were used for organ dosimetry. Contrast to noise ratio and signal to noise ratio were evaluated for image quality assessments. For this purpose, the region of the tooth and soft tissue images were randomly used as the basis.Results: Mean effective dose for face and paranasal sinuses imaging in three modes ( standard, low-dose, ultra-low dose), temporomandibular imaging in two modes(standard & low dose), and dental imaging in implant and endo imaging modes was equal to 382.17, 193.97, 79.96, 262.6, 135.67, 53.93, 682.83, 335.75, 184.18, and 234.57 μSv, respectively.Signal -to -noise ratio (SNR) for the above-mentioned procedures was equal to 6.04, 5.73, 3.71, 6.3, 6.00, 4.08, 14.2, 12.3, 7.51, and 6.97, respectively.Conclusion: The present study showed, when low dose and ultra-low-dose modes are chosen, the patient's dose will be severely reduced in most CBCT procedures. Contrast-to-noise ratio (CNR) and SNR will diminish too, but they are sufficient for some diagnostic purposes.

Background. Radiotherapy is a crucial treatment for most malignancies. However, it can cause several side effects, including the development of secondary malignancies due to radiation-induced genomic instability (RIGI). The aim of this study was to evaluate genomic instability in human mesenchymal stem cells (hMSCs) at different X-ray radiation doses. Additionally, the study aimed to examine the relative expression of certain genes involved in DNA repair, proto-oncogenes, and tumor suppressor genes. Methods. After extracting, characterizing, and expanding hMSCs, they were exposed to X-ray beams at doses of 0, 0.5, 2, and 6 Gy. Nuclear alterations were evaluated through the cytokinesis-block micronucleus (CBMN) assay at 2, 10, and 15 days postirradiation. The expressions of BRCA1, BRCA2, TP53, Bax, Bcl2, and KRAS genes were analyzed 48 hr after irradiation to evaluate genomic responses to different radiation doses. Results. The mean incidence of micronuclei, nucleoplasmic bridges, and nuclear buds was 4.8 ± 1.6, 47.6 ± 6, and 18 ± 2.6, respectively, in the nonirradiated group 48 hr after the fourth passage, per 1,000 binucleated cells. The incidence of micronuclei in groups exposed to 0.5, 2, and 6 Gy of radiation was 14.3 ± 4.9, 32.3 ± 6.5, and 55 ± 9.1, respectively, 48 hr after irradiation. The expression levels of the BRCA2, Bax, TP53, and KRAS genes significantly increased after exposure to 6 Gy radiation compared to the control groups. However, there was no significant increase in BRCA1 and Bcl2 gene expression in our study. Conclusion. This study demonstrated significant nuclear alterations in the 10 days postirradiation due to the RIGIs that they inherited from their irradiated ancestral cells. While chromosomal instability is a prevalent event in malignant cells, so it seems necessary to optimize radiotherapy treatment protocols for tissues that contain stem cells, especially with IMRT, which delivers a low dose to a larger volume of tissues.

The "Sacred Soul" is a term used by philosophers to often name a person who is severely alike. Mulla Sadra and Qazi Saeed both believe in the connection between this soul and the soul of the Prophet, which necessitates the recognition of its characteristics. In this paper, by direct reference to their works, in the first step, the features of the sacred soul are explained and then, by examining the relation of the holy soul and Prophetic soul, the question of the possibility of access of other human beings to the standard of the soul is evaluated. It must be said that the difference between the ontological and anthropological grounds of Mulla Sadra and Qazi Saeed has led to a difference of opinion between the two thinkers. According to the omnipotence of the existence and the formation of existence, the essential movement and the union of the intelligent and the intelligible ranks the arrogance for a sacred soul from the man that can Conjecture to the soul of the Prophet, but Qazi Saeed who did not accept these bases, reveals the instances of a sacred soul in the universal soul and the soul. Despite this difference in appearance, the relationship of the soul with the soul of the Prophet and other human populations in the thoughts of these two great philosophers is very close, to the extent that their difference of opinion cannot be regarded as a literal contribution of a sacred soul in their philosophical system.

Human fall is one of the key issues of anthropological concern in religious studies and philosophical investigations; it not only accounts for the nature of human soul rather it refers to the latter’s origin and its emergence. Although fall has been discussed in some prophetic traditions and sayings; for Mulla Sadra it is of philosophical interest and has been discussed along with the issues of soul’s origination. Thus this essay seeks to study the issue of human soul’s fall in the context of Mull Sadra’s philosophical discussions of soul as a whole and in view of a set of certain prophetic traditions. It aims at providing a picture of fall from a religious and philosophical point of view. Taking a problem-oriented approach, this research struggles to explain the bodily emergence and spiritual eternity of human soul and demonstrate that origination and fall are not of a contradictive or differentiated nature in Sadra’s view rather they are totally coherent; it also studies the philosophical, mystical and exegetical attitudes of Sadra on the existential status of human soul and its knowledge. Finally it seeks to offer a rational interpretation of ontological aspects of the fall of human soul drawing upon Sadra’s ideas concerning human realization.

Attention to practical philosophy is of a special place in the works of Farabi, Avicenna and Khajeh Nasir. The home management is concerned with family system and the place and roles of woman and man in home management. These three philosophers have common points as regards the principles and issues discussed in this area, but there are also considerable difference in their ideas regarding family and particularly woman. Drawing upon Greek philosophers, Farabi considers man an essentially civil entity and approaches the personality of woman with a humanist and virtue-centered perspective regardless of her gender. Avicenna and Khajeh Nasir have more functionalist view and insist mostly on the role of woman and man in family system. Of course, Khajeh has a more gender-related and less humanistic notion of woman and considers her as the servant of man whose main task is being a mother and a wife. Contrary to Farabi, he defines woman as phenomenon who should stay hidden at home and her exit from home and being in the society can result in undesirable consequences. The current essay assays the ideas of these three philosophers as well as their commonalities and differences as regards woman and home management.

The nanorods of [Pb(L)Br2]n (1) (L = 1,2-bis (pyridin-3-ylmethylene)hydrazine) underwent ultrasound irradiation and were synthesized as a novel three-dimensional fishbone-like Pb(II)–organic coordination supramolecular compound. The morphology and nanostructure of the synthesized compound were determined through SEM, FTIR, elemental analyses, and XRD. Compound 1 was structurally characterized by single-crystal X-ray diffraction and revealed six-coordinated Pb (II) ions bonded to two N atoms from two L ligands and four bromine anions, forming a one-dimensional fishbone-like coordination polymer, which extended into a 3D supramolecular structure through weak intermolecular interactions. The bulk thermal stability of compound 1 was examined using thermogravimetric analysis (TGA). Moreover, PbO nanoparticles with sizes of 40–80 nm were obtained through the thermolysis of 1 at 180 °C using oleic acid as a surfactant.

Objectives: The aim of this study was to evaluate the efficacy of a new psychiatry clerkship curriculum which was designed to improve the knowledge and skills of medical students of Tehran University of Medical Sciences (TUMS), Iran.Methods:This quasi-experimental study was conducted in two consecutive semesters from February 2009 to January 2010. In total, 167 medical students participated in the study. In the first semester, as the control group, the clerks’ training was based on the traditional curriculum. In the next semester, we constructed and applied a new curriculum based on the SPICES model (student-centered, problem-based, integrated, community-based, elective and systematic).At the end of the clerkship, the students were given two exams: Multiple Choice Questions (MCQ) to assess their knowledge, and Objective Structured Clinical Examination (OSCE) to assess their skills. Baseline data and test performance for each student were analyzed. Results:Compared to the control group, students in the intervention group showed significantly higher OSCE scores (P= 0.01). With respect to MCQ score, no significant difference was found between the two groups.Conclusions:The results suggest that the revised curriculum is more effective than the traditional one in improving the required clinical skills in medical students during their psychiatry clerkship.

The domain of ‘perceptions’ and ‘philosophy of action’ is a new and significant issue in Islamic philosophy. Our goal is to provide a consistent analysis of the place of two internal faculties - namely imagination and fancy - in the domain of human perceptions and actions. Regarding imagination as the place of particular forms, Mulla Sadra explains the function of these two faculties in multiple relations with other internal faculties. Seeing the imagination as a significant basis of action, Mulla Sadra explains the role of imagination as a link between sensible and intelligible world and like a habitus in keeping forms. This faculty is the source of arbitrary, habitual, natural and temperamental actions. Also fancy - as a perceiver of particular concepts - is the faculty of perception; With a expansion approach, we can promote the place of this faculty from ‘An intellective faculty along with other internal intellective faculties’ to a ‘dominant faculty on all animal faculties’ and even finally take the fancy equal to ‘animal soul’. And also fancy has a basic role in the intellective/ perceptive mistakes and its subsequent actions.

Objective: Bipolar spectrum disorders may often go undiagnosed or unrecognized. The aim of this study was to determine the proportion of bipolar disorder symptoms in Iranian patients with a major depressive episode.Methods: 313 patients with a current DSM-IV-TR (Diagnostic and Statistical Manual of Mental Disorders 4th ed. Text rev.) diagnosed with a major depressive episode entered this cross-sectional study. Thirty two items revised Hypomania/ mania Symptoms Checklist (HCL-32) was used to determine the frequency of bipolar episodes.Results: Considerable proportion of patients (53.9%) previously diagnosed as major depressive disorder fulfilled the criteria for bipolar disorder by Bipolarity Specifier. The Bipolarity Specifier additionally identified significant association for manic / hypomanic states during antidepressants therapy (p

According to some Western thinkers, considering earthy and compelled human alongside with the heavenly and compelling God can result in nothing but human’s alienation and transduction of alien personality in his mind and spirit. Basically, man’s realization of alienation and its type has a close relationship with the way of consideration of human and his nature. Of course type of human regard to God and kind of God that a religion defines, is another altered factor that into the side transaction, human and God has a decisive role. In Islamic teaching human nature and religion are defined as two truth corresponding together and in other words unique truth manifest into the sight of genesis and legislation as human nature and religion. In Islamic philosophy especially Hekmah Al-Motaaliyeh (transcendental wisdom) human’s relationship with God and also universe with God, is the same as relation and dependency. In heavenly instructions, human nature is divine whiff. Therefore, it should have total congruity with divine nature. Since self- forgetfulness is the direct result of God- forgetfulness, God-belief and self- detection have strong relation with each other, too. Moreover, in the mystical instructions of the Muslims mystics, God is a truth that is closer to man than himself. And therefore, the more he is such proximity , attraction and rapture to God, not only the man becomes self- alien , but also he will recognize himself better than before and will approach to his own origin.

The thesis of principality of existence is one of the most fundamental subjects of Islamic Philosophy. In a way most of the discussions of philosophical problems in this school are based on theosophy, and somehow they are tied to it. However Mullasudra raises the discussion of principality of existence with two different approaches in his works. One is a Gnostic approach, and the other is his own and innovative approach, Sadraei approach. In this paper we shall try to clarify the theory of principality of existence and compare the two approaches with each other, using the methodological tools, like discovering the basic questions, finding out the records and historical backgrounds, and requirements, as well as the consequences each involve.

Fluorescent in situ hybridization ( FISH ) is a new diagnostic technique for specific detection of microorganisms at molecular level and direct visualization of microbial morphology. In this study, FISH technique was evaluated for detection of staphylococci. A set of 16S rRNA-targeted oligonucleotide probes were used for FISH. For detection of Staphylococcus aureus in sputum samples by FISH and comparison with conventional bacterial culture, 76 sputum samples were investigated . According to our data , sensitivity and specificity of FISH for detection of this bacterium were 86.7% and 100% , respectively. As another part of this study, 41 blood culture specimens were examined for detection of staphylococci. In compare with conventional culture methods, sensitivity and specificity of FISH for detection of S. aureus were 100% and for non S. aureus species of staphylococci, sensitivity and specificity of FISH were 95.7% and 100% respectively. All steps of FISH technique were performed within 3h. Therefore, FISH is a rapid, sensitive, and specific technique for detection of staphylococci.

Abstract: "nIn developing countries, little evidence is available on the mental health status of health care providers, especially doctors. Therefore, the aim of this study is to obtain an estimation on the prevalence of depression amongresident doctors of medical universities in Tehran, Iran. "n "n "nMethod: "nThe study population consisted of 2251 resident doctors who worked in the hospitals of 3 medical universities located in Tehran.Beck Depression Inventory (BDI) was used as the main instrument of thisresearch "n "n "nResults: "nThe response rate was 68.28%.31.2% of the total study population had symptoms of depression (26% of the males and 39% of the females).Symptoms of depression were 2.3 times more frequent in females. Mostdepressed physicians did not have a history of psychiatric visit or treatment.Conclusion: "n "nThis study demonstrates that depression is common among Iranian residents(particularly in females); however, most of them do not seek any treatment. This may lead to serious impacts on health behavior of the community in general.Moreover, depression may seriously affect physicians' professional function.

Objectives: The aim of this study was to evaluate the efficacy of a new psychiatry clerkship curriculum which was designed to improve the knowledge and skills of medical students of Tehran University of Medical Sciences (TUMS), Iran. Methods:This quasi-experimental study was conducted in two consecutive semesters from February 2009 to January 2010. In total, 167 medical students participated in the study. In the first semester, as the control group, the clerks’ training was based on the traditional curriculum. In the next semester, we constructed and applied a new curriculum based on the SPICES model (student-centered, problem-based, integrated, community-based, elective and systematic).At the end of the clerkship, the students were given two exams: Multiple Choice Questions (MCQ) to assess their knowledge, and Objective Structured Clinical Examination (OSCE) to assess their skills. Baseline data and test performance for each student were analyzed. Results: Compared to the control group, students in the inter ention group showed significantly higher OSCE scores (P= 0.01). With respect to MCQ score, no significant difference was found between the two groups. Conclusions: The results suggest that the revised curriculum is more effective than the traditional one in improving the required clinical skills in medical students during their psychiatry clerkship.

Objective: To report the case of a 28-year old hypercholesterolemic female with postpartum depression, whose triglyceride (TG) and total cholesterol (TC) levels decreased while being treated with fluoxetine. Method: A 28-year old female, with a diagnosis of major depressive disorder with postpartum onset based on DSM-IV criteria, was hospitalized at a mental health hospital. Her past history included another episode of depression 4 months after giving birth to her second child, which was 12 years prior to her recent episode. Her serum total cholestrol and triglyceride levels were measured prior to the initiation of medication. Then fluoxetine was initiated at a daily dose of 20 mg and had been increased to 40 mg per day at the time of discharge. The lipid profile measurements was repeated at week 4 and 8 following treatment. Results: Total cholesterol level was reduced from 242 mg/dL at baseline to 224 mg/dL at week 4 and to 202 mg/dL at week 8; triglyceride level was decreased from 516 mg/dL to 448 mg/dL at week 4 and to 404 mg/dL at week 8. Conclusions: Fluoxetine may be an appropriate treatment for hyperlipidemic women with postpartum depression.

Abstract The CRISPR system finds extensive application in molecular biology, but its continuous activity can yield adverse effects. Leveraging programmable CRISPR/Cas9 function via nano-device mediation effectively mitigates these drawbacks. The integration of RNA-sensing platforms into CRISPR thus empowers it as a potent tool for processing internal cell data and modulating gene activity. Here, an intelligent guide RNA—a cis-repressed gRNA synthetic circuit enabling efficient recognition of specific trigger RNAs—is developed. This platform carries two toehold switches and includes an inhibited CrRNA sequence. In this system, the presence of cognate trigger RNA promotes precise binding to the first toehold site, initiating a cascade that releases CrRNA to target a reporter gene (luciferase) in this study. Decoupling the CrRNA segment from the trigger RNA enhances the potential of this genetic logic circuit to respond to specific cellular circumstances, offering promise as a synthetic biology platform.

Abstract Background Nano-drug delivery systems have become a promising approach to overcoming problems such as low solubility and cellular uptake of drugs. Along with various delivery devices, dendrimers are widely used through their unique features. PEG-citrate dendrimers are biocompatible and nontoxic, with the ability to improve drug solubility. Curcumin, a naturally occurring polyphenol, has multiple beneficial properties, such as antiviral activities. However, its optimum potential has been significantly hampered due to its poor water solubility, which leads to reduced bioavailability. So, the present study attempted to address this issue and investigate its antiviral effects against HIV-1. Method The G2 PEG-citrate dendrimer was synthesized. Then, curcumin was conjugated to it directly. FTIR, HNMR, DLS, and LCMS characterized the structure of products. The conjugate displayed an intense yellow color. In addition, increased aqueous solubility and cell permeability of curcumin were achieved based on flow cytometry results. So, it could be a suitable vehicle for improving the therapeutic applications of curcumin. Moreover, cell toxicity was assessed using XTT method. Ultimately, the SCR HIV system provided an opportunity to evaluate the level of HIV-1 inhibition by the curcumin-dendrimer conjugate using a p24 HIV ELISA kit. Results The results demonstrated a 50% up to 90% inhibition of HIV proliferation at 12 μm and 60 μm, respectively. Inhibition of HIV-1 at concentrations much lower than CC50 (300 µM) indicates a high potential of curcumin-dendrimer conjugate against this virus. Conclusion Thereby, curcumin-dendrimer conjugate proves to be a promising tool to use in HIV-1 therapy.

Abstract Background Drug combination therapy is preferred over monotherapy in clinical research to improve therapeutic effects. Developing a new nanodelivery system for cancer drugs can reduce side effects and provide several advantages, including matched pharmacokinetics and potential synergistic activity. This study aimed to examine and determine the efficiency of the gemini surfactants (GSs) as a pH-sensitive polymeric carrier and cell-penetrating agent in cancer cells to achieve dual drug delivery and synergistic effects of curcumin (Cur) combined with tamoxifen citrate (TMX) in the treatment of MCF-7 and MDA-MB-231 human BC cell lines. Methods The synthesized NPs were self-assembled using a modified nanoprecipitation method. The functional groups and crystalline form of the nanoformulation were examined by Fourier-transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), differential scanning calorimetry (DSC), and dynamic light scattering (DLS) used to assess zeta potential and particle size, and the morphological analysis determined by transmission electron microscopy (TEM). The anticancer effect was evaluated through an in vitro cytotoxicity MTT assay, flow cytometry analysis, and apoptosis analysis performed for mechanism investigation. Results The tailored NPs were developed with a size of 252.3 ± 24.6 nm and zeta potential of 18.2 ± 4.4 mV capable of crossing the membrane of cancer cells. The drug loading and release efficacy assessment showed that the loading of TMX and Cur were 93.84% ± 1.95% and 90.18% ± 0.56%, respectively. In addition, the drug release was more controlled and slower than the free state. Polymeric nanocarriers improved controlled drug release 72.19 ± 2.72% of Tmx and 55.50 ± 2.86% of Cur were released from the Tmx-Cur-Gs NPs after 72 h at pH = 5.5. This confirms the positive effect of polymeric nanocarriers on the controlled drug release mechanism. moreover, the toxicity test showed that combination-drug delivery was much more greater than single-drug delivery in MCF-7 and MDA-MB-231 cell lines. Cellular imaging showed excellent internalization of TMX-Cur-GS NPs in both MCF-7 and MDA-MB-231 cells and synergistic anticancer effects, with combination indices of 0.561 and 0.353, respectively. Conclusion The combined drug delivery system had a greater toxic effect on cell lines than single-drug delivery. The synergistic effect of TMX and Cur with decreasing inhibitory concentrations could be a more promising system for BC-targeted therapy using GS NPs.

Abstract Introduction Depression and anxiety are pervasive mental health disorders with substantial global burdens. Probiotics, live microorganisms known for their health benefits, have emerged as a potential therapeutic intervention for these conditions. This systematic review and meta-analysis aim to evaluate the strain-specific effects of probiotics on relieving depressive and anxiety symptoms while elucidating underlying mechanisms. Methods EMBASE, Cochrane CENTRAL and PubMed/Medline were systematically queried to identify studies released until May 15, 2024. Randomized Controlled Trials (RCTs) that employed standardized assessment tools for depression and anxiety namely Beck Depression Inventory (BDI), Hamilton Depression Rating Scale (HAMD), Depression Anxiety Stress Scales (DASS), or Montgomery-Asberg Depression Rating Scale (MADRS) were included. Results 12 RCTs involving 707 participants were included. Seven RCTs utilizing the BDI questionnaire demonstrated a significant decrease in depressive symptoms favoring probiotics containing strains such as Lactobacillus acidophilus, Lactobacillus paracasei, Lactobacillus casei, Lactobacillus plantarum, Lactobacillus salivarius, Bifidobacterium bifidum, Bifidobacterium lactis, Bifidobacterium breve, and Bifidobacterium longum (MD: -2.69, CI95%: -4.22/-1.16, p value: 0.00). Conversely, RCTs using HAMD showed a non-significant reduction in depressive symptoms (MD: -1.40, CI95%: -3.29/0.48, p value: 0.14). RCTs employing DASS and MADRS scales also showed no significant differences. Conclusion This meta-analysis offers valuable insights into the strain-specific effects of probiotics containing Lactobacillus and Bifidobacterium species on depressive and anxiety symptoms. While our findings suggest a significant reduction in depressive symptoms based on the BDI scale favoring probiotics, the lack of significant effects observed on the HAMD, DASS, and MADRS scales underscores the complexity inherent in these conditions. It is imperative to acknowledge the mixed results across different measurement scales, indicating the need for cautious interpretation. Therefore, we advocate for a nuanced understanding of probiotics’ impacts on various dimensions of mood, emphasizing the necessity for further research.

Abstract In this study we develop novel type of antibacterial chitosan-propolis NPs to improve theantimicrobial activity against various pathogens. To this aim, we primarily extracted propolis with methylal and ethanol as green solvents and its encapsulation with chitosan NPs. The developed propolis loaded chitosan NPs indicated antimicrobial and anti-biofilm properties against various gram positive and negative. FTIR revealed the successful encapsulation of the propolis extract with Ethanol (PE) and Methylal (PM) into the chitosan nano career matrix. HPLC and GC-MASS also confirmed the presence of flavonoids and phenols compounds of propolis extracted with both solvents. In addition, we confirmed the total phenolic and flavonoid compounds in propolis by calorimetric method of Folin–Ciocalteu and aluminum trichloride complex formation assays, respectively. PE-CH and PM-CH were optimized regarding physicochemical properties such as particle size, zeta potential, and poly dispersity index (PDI) index. DLS and SEM micrographs confirmed a spherical morphology in a range of 360–420 nm with Z potential values of 30–48 mV and PDI of 0.105–0.166 for PE-CH and PM-CH, respectively. The encapsulation efficiency was evaluated using colorimetric analysis, with median values ranging from 90 to 92%. The MIC values within the range of 2 to 230 µg/ml and MBC values between 3 to 346 μg/ml against both gram-positive and negative bacteria. While both PE and PM showed a significant reduction in the number of E. coli, S. aureus, and S. epidermidis, the use of PE-CH and PM-CH led to a statistically significant and greater reduction in number of E. coli, S. aureus, and S. epidermidis strains on the biofilm, pre-formed biofilm and planktonic phases. Besides, the DPPH assay showed significant antioxidant activity for these NPs within the range of 36 to 92%. MTT assay for MHFB-1, HFF, L929, MDF, and MCF-7 cells exhibited statistically significant differences in each other that show the IC50 between 60–160 µg/ml for normal cells and 20 for cancer cells. Finally the present study indicated that both PM and PM-CH greater than PE and PE-CH in which contain high flavonoid and phenolic contents with a high antioxidation potential antioxidant properties, which could be beneficial for cell proliferation and antibiotic and anticancer applications.

Abstract MicroRNA expression in breast cancer (BC) is explored both as a potential biomarker and for therapeutic purposes. Recent studies have revealed that miR-203a-3p is involved in BC, and importantly contributes to BC chemotherapy responses; however, the regulatory pathways of miR-203a in BC remain elusive. Hence, we aimed to investigate the miR-203a regulatory mechanisms and their potential functions in the progress of BC. To this end, the miR-203a potential involving pathways was predicted by databases analyzing its target genes. The relations between miR-203a, the phosphatidylinositol 3′-kinase (PI3K)–Akt, and Wnt signaling pathways were mechanistically investigated. Our results revealed that miR-203a inhibited the activation of the PI3K/Akt and Wnt pathways and reduced its downstream cell cycle signals, including Cyclin D1 and c-Myc. Moreover, the overexpression of miR-203a drastically arrested the cell cycle at subG1 and G1 phases, decreased the viability, proliferation, and migration, and increased apoptosis of BC cells. Therefore, miR-203a-3p may be considered a tumor suppressor factor and a potential biomarker or therapeutic target for BC.

Abstract In type 1 diabetes, the immune system destroys pancreatic beta cells in an autoimmune condition. To overcome this disease, a specific monoclonal antibody that binds to pancreatic beta cells could be used for targeted immunotherapy. Protein tyrosine phosphatase receptor N (PTPRN) is one of the important surface antigen candidates. Due to its high sequence homology among mammals, so far, no single-chain monoclonal antibody has been produced against this receptor. In this study, we developed a novel single-chain variable fragment (scFv) against the PTPRN extracellular domain. To this aim, ostrich species was used as a host is far phylogenetically birds from mammals to construct a phage display library for the first time. An ostrich-derived scfv phage display library was prepared and biopanning steps were done to enrich and screen for isolating the best anti-PTPRN binders. An scFv with appropriate affinity and specificity to the PTPRN extracellular domain was selected and characterized by ELISA, western blotting, and flow cytometry. The anti-PTPRN scFv developed in this study could be introduced as an effective tool that can pave the way for the creation of antibody-based targeting systems in cooperation with the detection and therapy of type I diabetes.

Abstract Background GBM is the most frequent malignant primary brain tumor in humans. The CLEC19A is a member of the C-type lectin family, which has a high expression in brain tissue. Herein, we sought to carry out an in-depth analysis to pinpoint the role of CLEC19A expression in GBM. Methods To determine the localization of CLEC19A, this protein was detected using Western blot, Immunocytochemistry/Immunofluorescence, and confocal microscopy imaging. CLEC19A expression in glioma cells and tissues was evaluated by qRT-PCR. Cell viability, proliferation, migration, and apoptosis were examined through MTT assay, CFSE assay, colony formation, wound healing assay, transwell test, and flow cytometry respectively after CLEC19A overexpression. The effect of CLEC19A overexpression on the PI3K/AKT/NF-κB signaling pathway was investigated using Western blot. An in vivo experiment substantiated the in vitro results using the glioblastoma rat models. Results Our in-silico analysis using TCGA data and measuring CLEC19A expression level by qRT-PCR determined significantly lower expression of CLEC19A in human glioma tissues compared to healthy brain tissues. By employment of ICC/IF, confocal microscopy imaging, and Western blot we could show that CLEC19A is plausibly a secreted protein. Results obtained from several in vitro readouts showed that CLEC19A overexpression in U87 and C6 glioma cell lines is associated with the inhibition of cell proliferation, viability, and migration. Further, qRT-PCR and Western blot analysis showed CLEC19A overexpression could reduce the expression levels of PI3K, VEGFα, MMP2, and NF-κB and increase PTEN, TIMP3, RECK, and PDCD4 expression levels in glioma cell lines. Furthermore, flow cytometry results revealed that CLEC19A overexpression was associated with significant cell cycle arrest and promotion of apoptosis in glioma cell lines. Interestingly, using a glioma rat model we could substantiate that CLEC19A overexpression suppresses glioma tumor growth. Conclusions To our knowledge, this is the first report providing in-silico, molecular, cellular, and in vivo evidences on the role of CLEC19A as a putative tumor suppressor gene in GBM. These results enhance our understanding of the role of CLEC19A in glioma and warrant further exploration of CLEC19A as a potential therapeutic target for GBM.

Objective: Type 1 diabetes (T1Ds) is an autoimmune disease in which the immune system invades and destroysinsulin-producing cells. Nevertheless, at the time of diagnosis, about 30-40% of pancreatic beta cells are healthy andcapable of producing insulin. Bi-specific antibodies, chimeric antigen receptor regulatory T cells (CAR-Treg cells), andlabeled antibodies could be a new emerging option for the treatment or diagnosis of type I diabetic patients. The aimof the study is to choose appropriate cell surface antigens in the pancreas tissue for generating an antibody for type Idiabetic patients.Materials and Methods: In this bioinformatics study, we extracted pancreas-specific proteins from two largedatabases; the Human Protein Atlas (HPA) and Genotype-Tissue Expression (GTEx) Portal. Pancreatic-enrichedgenes were chosen and narrowed down by Protter software for the investigation of accessible extracellular domains.The immunohistochemistry (IHC) data of the protein atlas database were used to evaluate the protein expression ofselected antigens. We explored the function of candidate antigens by using the GeneCards database to evaluate thepotential dysfunction or activation/hyperactivation of antigens after antibody binding.Results: The results showed 429 genes are highly expressed in the pancreas tissue. Also, eighteen genes encodedplasma membrane proteins that have high expression in the microarray (GEO) dataset. Our results introduced fourstructural proteins, including NPHS1, KIRREL2, GP2, and CUZD1, among all seventeen candidate proteins.Conclusion: The presented antigens can potentially be used to produce specific pancreatic antibodies that guide CARTreg,bi-specific, or labeling molecules to the pancreas for treatment, detection, or other molecular targeted therapyscopes for type I diabetes.

Introduction: Cone-beam computed tomography is used for specialized imaging of dental and maxillofacial structures. CBCTs capabilities and facilities for dental and maxillofacial imaging have resulted in their increasing clinical use. Although the dose of CBCT tests is low, its widespread use increases the cumulative dose. This study was conducted to evaluate head and neck effective dose and image quality in different organs for various exposure techniques in CBCT imaging. Material and Methods: This study was performed on various CBCT imaging examinations. Head and neck parts of anthropomorphic male Rando® Alderson Phantom and thermoluminescent dosimeters were used for organ dosimetry. Contrast to noise ratio and signal to noise ratio were evaluated for image quality assessments. For this purpose, the region of the tooth and soft tissue images were randomly used as the basis. Results: Mean effective dose for face and paranasal sinuses imaging in three modes (standard, low-dose, ultra-low dose), temporomandibular imaging in two modes(standard & low dose), and dental imaging in implant and endo imaging modes was equal to 382.17, 193.97, 79.96, 262.6, 135.67, 53.93, 682.83, 335.75, 184.18, and 234.57 µSv, respectively. Signal -to -noise ratio (SNR) for the above-mentioned procedures was equal to 6.04, 5.73, 3.71, 6.3, 6.00, 4.08, 14.2, 12.3, 7.51, and 6.97, respectively. Conclusion: The present study showed, when low dose and ultra-low-dose modes are chosen, the patient's dose will be severely reduced in most CBCT procedures. Contrast-to-noise ratio (CNR) and SNR will diminish too, but they are sufficient for some diagnostic purposes. [ABSTRACT FROM AUTHOR]

Lymphoid organs are the main structural components of the immune system. In the current research, the mixture of poly lactic-co-glycolic acid (PLGA), polycaprolactone (PCL), and M13 phage or its RGD-modified form was used in the construction of a fibrillar scaffold using the electrospinning method. The constructs were transplanted intra-abdominally and examined for the formation of lymphoid-like tissues at different time intervals. The confocal and scanning electron microscopy demonstrate that M13 phage-containing scaffolds provide a suitable environment for lymph node-isolated fibroblasts. Morphological analysis demonstrate the formation of lymph node-like tissues in the M13 phage-containing scaffolds after transplantation. Histological analysis confirm both blood and lymph angiogenesis in the implanted construct and migration of inflammatory cells to the M13 phage-containing scaffolds. In addition, flow cytometry and immunohistochemistry analysis showed the homing and compartmentalization of dendritic cells (DCs), B and T lymphocytes within the PLGA/PCL/M13 phage-RGD based scaffolds and similar to what is seen in the mouse lymphoid tissues. It seems that the application of M13 phage could improve the generation of functional lymphoid tissues in the electrospun scaffolds and could be used for lymphoid tissue regeneration.

Objective(s): Targeting the lytic cycle of the Epstein-Barr virus (EBV) has been considered a new treatment strategy for malignancies caused by this virus. This study aimed to investigate the effect of Dendrosomal NanoCurcumin (DNC) to prevent cell transformation and inhibit the expression of viral lytic gene expression in the generation of lymphoblastoid cell line (LCL).Materials and Methods: Cell viability of LCLs and PBMCs was performed by MTT assay, and flow cytometry (Annexin/PI) was used for evaluation of apoptosis. CD markers on the surface of generated LCL (CD19) cells were examined for cell validation. The effect of DNC on transformation was evaluated by examining cell morphology and determining the expression level of lytic genes BZLF1, Zta, BHRF1, and BRLF1 of EBV using Real-time PCR. Student’s t-test was used for statistical analysis.Results: The MTT assay showed that DNC can inhibit the proliferation of LCL in a dose-dependent manner. The 50% cytotoxic concentration (CC50) of DNC and curcumin for LCL was determined 38.8 µg/ml and 75 µg/ml, respectively after 72 hr. Also, Real-time PCR data analysis showed that DNC in 30 µg/ml concentration significantly inhibited cell transformation in the LCL and significantly reduced viral lytic genes such as BZLF1, Zta, BHRF1, and BRLF1expression compared to control.Conclusion: Overall, these findings show that DNC reduces the expression of the viral lytic cycle genes and also the induction of cell apoptosis and finally prevents the generation of LCL.

Abstract Background Hepatocellular Carcinoma (HCC) is a prevalent form of liver cancer that causes significant mortality in numerous individuals worldwide. This study compared the effects of milk thistle (MT) and nano-milk thistle (N-MT) on the expression of the genes that participate in apoptosis and cell cycle pathways in Huh-7 and HepG2 cells. Methods IC50 values of MT and N-MT were determined using the MTT assay. Huh-7 and HepG2 cell lines (containing mutant and wild-type TP53 gene, respectively) were incubated with MT and N-MT for 24h and 48h and the impact of MT and N-MT on the proliferation of these cell lines was evaluated through a comparative analysis. Cell cycle and apoptosis were assessed by flow cytometry after 24h and 48h treatment in the cell lines mentioned. Real-time PCR was used to analyze miR-155-3p, PHLDA1, SOCS2, TP53, P21, BAX, and BCL-2 expression in the cell lines that were being treated. Results N-MT reduces cancer cell growth in a time and concentration-dependent manner, which is more toxic compared to MT. Huh-7 was observed to have IC50 values of 2.35 and 1.7 μg/ml at 24h and 48h, and HepG2 was observed to have IC50 values of 3.4 and 2.6 μg/ml at 24 and 48h, respectively. N-MT arrested Huh-7 and HepG2 cells in the Sub-G1 phase and induced apoptosis. N-MT led to a marked reduction in the expression of miR-155-3p and BCL-2 after 24h and 48h treatments. Conversely, PHLDA1, SOCS2, BAX, and P21 were upregulated in the treated cells compared to untreated cells, which suggests that milk thistle has the potential to regulate these genes. N-MT reduced the expression of TP53 in Huh-7 cells after mentioned time points, while there was a significant increase in the expression of the TP53 gene in HepG2 cells. No gene expression changes were observed in MT-treated cells after 24h and 48h. Conclusion N-MT can regulate cancer cell death by arresting cell cycle and inducing apoptosis. This occurs through the alteration of apoptotic genes expression. A reduction in the expression of miR-155-3p and increase in the expression of SOCS2 and PHLDA1 after N-MT treatment showed the correlation between miR-155-3p and PHLDA1/SOCS2 found in bioinformatics analysis. While N-MT increased TP53 expression in HepG2, reduced it in Huh-7. The findings indicate that N-MT can function intelligently in cancer cells and can be a helpful complement to cancer treatment.

Purpose: Chemotherapy drugs used to treat lung cancer are associated with drug resistance and severe side effects. There have been rising demands for new therapeutic candidates and novel approaches, including combination therapy. Here, we aimed to investigate the combinatorial effect of a dendrosomal formulation of curcumin (DNC) and daunorubicin (DNR) on the A549 lung cancer cell line. Methods: We performed cytotoxicity, apoptosis, cell migration, colony-formation capacity, and gene expression analysis to interpret the mechanism of action for a combination of DNC and DNR on A549 cells. Results: Our results revealed that the combination of DNC and DNR could synergistically inhibit the A549 cells’ growth. This synergistic cytotoxicity was further approved by flow cytometry, migration assessment, colony-forming capacity and gene expression analysis. DNR combination with DNC resulted in increased apoptosis to necrosis ratio compared to DNR alone. In addition, the migration and colony-forming capacity were at the minimal range when DNC was combined with DNR. Combined treatment decreased the expression level of MDR-1, hTERT and Bcl-2 genes significantly. In addition, the ratio of Bax/Bcl2 gene expression significantly increased. Our analysis by free curcumin, dendrosomes and DNC also showed that dendrosomes do not have any significant cytotoxic effect on the A549 cells, suggesting that this carrier has a high potential for enhancing the curcumin’s biological effects. Conclusion: Our observations suggest that the DNC formulation of curcumin synergistically enhances the antineoplastic effect of DNR on the A549 cell line through the modulation of apoptosis/necrosis ratio, as well as Bax/Bcl2 ratio, MDR-1 and hTERT gene expression.

Abstract Chimeric antigen receptor (CAR) T cells and natural killer (NK) cells are genetically engineered immune cells that can detect target antigens on the surface of target cells and eliminate them following adoptive transfer. Recent progress in CAR-based therapies has led to outstanding clinical success in certain patients with leukemias and lymphomas and offered therapeutic benefits to those resistant to conventional therapies. The universal approach to stable CAR transgene delivery into the T/NK cells is the use of viral particles. Such approaches mediate semi-random transgene insertions spanning the entire genome with a high preference for integration into sites surrounding highly-expressed genes and active loci. Regardless of the variable CAR expression level based on the integration site of the CAR transgene, foreign integrated DNA fragments may affect the neighboring endogenous genes and chromatin structure and potentially change a transduced T/NK cell behavior and function or even favor cellular transformation. In contrast, site-specific integration of CAR constructs using recent genome-editing technologies could overcome the limitations and disadvantages of universal random gene integration. Herein, we explain random and site-specific integration of CAR transgenes in CAR-T/NK cell therapies. Also, we tend to summarize the methods for site-specific integration as well as the clinical outcomes of certain gene disruptions or enhancements due to CAR transgene integration. Also, the advantages and limitations of using site-specific integration methods are discussed in this review. Ultimately, we will introduce the genomic safe harbor (GSH) standards and suggest some appropriate safety prospects for CAR integration in CAR-T/NK cell therapies.