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Various Effects of the GABAergic System on Cancer: The Conditions and Specificities of its use in the Treatment of Some Cancers
No full textGABA is an essential neurotransmitter in tissues other than the brain and has different functions. Cancer displays dysfunctional GABAergic system roles, comprising GAD, GABA, and GABA receptors. Both tumor-suppressing and carcinogenic characteristics of the GABAergic system have been reported in several malignancies. In the development of cancer cells, it plays oncogenesis-related roles. However, in some tumors, such as pancreatic cancer, it exhibits anti-cancer benefits in numerous human trials and animal models. As a result, GABAergic therapy may be used to treat cancer. The oxidative condition and the status of several malignant circumstances significantly influence the final GABAergic function in many tumors. Depending on the type of malignant tissue and other modifications, these roles manifest differently in malignancies. In this review, we, for the first time, concentrated on the oncogenic and tumor suppressor functions of GABA in various neoplasms, as well as its potential therapeutic implications. The significance of tumor suppressor function and the conditions that promote its function as a cancer genesis factor in cancer are discussed in this article
Circular RNAs: Novel Biomarkers in Spermatogenesis Defects and Male Infertility
No full textCircular RNAs (circRNAs) are a new class of endogenous non-coding RNAs involved in several cellular and biological processes, including gene expression regulation, microRNA function, transcription regulation, and translation modification. Therefore, these non-coding RNAs have important roles in the pathogenesis of various diseases. Male infertility is mainly due to abnormal sperm parameters such as motility, morphology, and concentration. Recent studies have confirmed the role of circRNAs in spermatogenesis, and the expression of several circRNAs is confirmed in seminal plasma, spermatozoa, and testicular tissue. It is suggested that deregulation of circRNAs is involved in different types of male infertility, including azoospermia, oligozoospermia, and asthenozoospermia. In the present review, we aimed to discuss the potential roles of circRNAs in spermatogenesis failure, sperm defects, and male infertility. Due to their conserved and special structure and tissue-specific expression pattern, circRNAs can be applied as reliable noninvasive molecular biomarkers, therapeutic and pharmaceutical targets in male infertility
Chitosan/alginate bionanocomposites adorned with mesoporous silica nanoparticles for bone tissue engineering
No full textThe regeneration of oral and craniofacial bone defects ranging from minor periodontal and peri-implant defects to large and critical lesions imposes a substantial global health burden. Conventional therapies are associated with several limitations, highlighting the development of a unique treatment strategy, such as tissue engineering. A well-designed scaffold for bone tissue engineering should possess biocompatibility, biodegradability, mechanical strength, and osteoconductivity. For this purpose, mesoporous silica nanoparticles (MSNs) were synthesized and incorporated at different ratios (10, 20, and 30%) into alginate/chitosan (Alg/Chit)-based porous composite scaffolds fabricated through the freeze-drying method. The MSN incorporation significantly improved the mechanical strength of the scaffolds while showing a negligible decreasing effect on the porosity. All of the samples showed desirable swelling behaviors, which is beneficial for cell attachment and proliferation. The MSN-containing scaffolds indicated a decreased hydrolytic degradation in an MSN percentage-dependent manner. The fabricated scaffolds did not depict cytotoxic characteristics. The Alg/Chit/MSN30 scaffolds not only showed noncytotoxic properties, but also increased the cell viability significantly compared to the control group. The biomineralization properties of the MSN-containing nanocomposite scaffolds were significantly higher than the Alg/Chit composite, suggesting the potential of these nanoparticles for bone tissue engineering applications. Taken together, it is concluded that the Alg/Chit/MSN30 scaffolds are considerable substances for bone tissue regeneration, and MSN has a great tissue engineering potential in addition to its extensive biomedical applications
Dual Targeting of Anti-Apoptotic Proteins Enhances Chemosensitivity of the Acute Myeloid Leukemia Cells
No full textBACKGROUND: Acute myeloid leukemia (AML) is a type of blood cancer characterized by fast cellular proliferation. Myeloid cell leukemia-1 (Mcl-1) and survivin, as anti-apoptotic proteins, are involved in cancer growth and resistance to chemotherapy. The aim of this study was to examine the combination effect of Mcl-1 and survivin specific siRNAs on chemosensitivity of the human HL-60 AML cells. METHODS: SiRNAs transfection was performed by using Lipofectamine™2000 reagent. The mRNA expression was analyzed by real-time quantitative PCR. The apoptosis analysis was measured by ELISA cell death assay. RESULTS: siRNAs markedly suppressed mRNA expression levels of Mcl-1 and survivin in a time-dependent manner, resulting in reduction of leukemic cell proliferation and enhanced spontaneous cell death. Surprisingly, Mcl-1 siRNA and survivin siRNA synergistically enhanced the cell toxic effects of etoposide. Furthermore, down-regulation of Mcl-1 and survivin significantly enhanced the apoptotic effect of etoposide. CONCLUSIONS: Our investigation suggests that suppression of Mcl-1 and survivin by siRNA can effectually inhibit cell growth and overcome chemoresistance of AML cells. Therefore siRNAs may be an important adjuvant in chemotherapy for AML patients
Alemtuzumab‐induced petechiae and epistaxis in a patient with relapsing–remitting multiple sclerosis: A case report
No full textHere, we present a case of relapsing-remitting multiple sclerosis that experienced petechiae and epistaxis following treatment with second dose of alemtuzumab. This study highlights such effects, emphasizing the need for vigilance as alemtuzumab usage increases. Timely recognition and management are vital for patient care.
Alemtuzumab-induced petechiae and epistaxis in a patient with relapsing-remitting multiple sclerosis.imag
Lessons from Self-Assessment of Post-Rhinoplasty Complaints; Analysis of 192 Candidates of Secondary Rhinoplasty
No full textBackground: Rhinoplasty as the most common aesthetic surgical operations aims to correct deformities of the different structures of the nose with each case its own challenges. We aimed to highlight the importance of self-assessment for rhino surgeons.
Methods: This retrospective descriptive study was done on 192 patients in Ordibehesht Hospital, Isfahan, Iran from April 2017 to Jun 2021. candidate for secondary rhinoplasty, with mandatory aesthetic and optional functional purposes, having previously undergone rhinoplasty with the same or another surgeon. Patients with initial rhinoplasty by the first author were assigned to group 1 (n=102) and the patients who were operated by the other surgeons were in the group 2 (n=90). Data were collected using an author made checklist divided into three parts: overall demographic questions, questions about the patients' aesthetic and functional complaints and objective evaluation by the surgeon.
Results: The most frequent reported complaints led to their current rhinoplasty were about the nasal tip with 161 cases (83.9%), upper nasal part with 98 cases (51%) and mid-nose (middle nose) with 81 cases (42.2%). Besides, respiratory problem was observed in 58 patients (30.2%). Surgeon's skill was significantly associated with occurrence of these two complaints; so that these two complaints were more common in group2 than group1 (P value <0.05).
Conclusion: Such assessments resulted to improve the surgical outcomes due to finding the more prevalent problems in own patients than the other surgeons' patients and determining the reasons that leads to change the techniques with regard to the researches and consulting with the colleagu
Evaluation of Apoptosis-Related Genes and Hormone Secretion Profiles Using Three Dimensional Culture System of Human Testicular Organoids
No full textBackground: In reproductive biology, testicular organoids can be used to treat infertili-ty and to study testicular development and spermatogonial stem cells (SSCs) differentiation. Generating organoid from primary cells is challenging. In this study, testicular organoids were created using human primary testicular cells and evaluated the apoptotic gene expres-sion and hormone secretion profiles of the organoids. Materials and Methods: Primary hu-man testicular cells were isolated using 2-step enzymatic digestion from three brain-dead do -nors. Immunocytochemistry and flow cytometry analyses were performed to confirm human SSCs. Isolated cells were cultured in three experimental groups: control group (2 dimension -al (2D)), group 1 (organoid culture after 2D culture), and group 2 (organoid culture imme-diately after enzymatic digestion). Testicular organoids were cultured in DMEM/F-12 media supplemented with follicle-stimulating hormone (FSH) and fetal bovine serum (FBS) for four weeks. After 24 hours and four weeks of culture, reverse transcription quantitative real-time PCR (RT-qPCR) was used to investigate the relative expression of apoptotic genes (caspase 3, 9, Bax, and Bcl-2). At 24 hours, two weeks, and four weeks after culture, enzyme-linked immunoassay (ELISA) was used to determine the testosterone and inhibin B concentrations. Light microscopy and toluidine blue staining were also used for morphological analysis. Re-sults: RT-qPCR results revealed that pro-apoptotic (caspase 3, 9, Bax) gene expression lev -els were highest in group 2 after 24 h and four weeks of culture. In contrast, the expression level of Bcl-2 (anti-apoptotic) was lower in group 2 compared to other groups. The hormone secretion levels decreased in a time-dependent manner during the cultivation. According to morphological evaluations, testicular organoids are compact, spherical structures with two to three elongated cells organized along their border. Conclusion: Our findings revealed that the testicular organoid culture system maintained hormonal secretory abilities, demonstrat-ing the function of Sertoli and Leydig cells in the absence of testis-specific environments
Examining the effect of safety climate on accident risk through job stress: a path analysis
No full textBackground: Job stress is a probable mediator of the relationship between safety climate and accident occurrence. To demonstrate this, this study investigates the relationship between safety climate, job stress, and accident risk using a large number of surveys. The study will use structural equation modeling (SEM) to analyze the data collected from the surveys to examine the effect of safety climate on accident risk through job stress. Methods: The study is a cross-sectional study that was conducted on 1,530 male workers of a petrochemical company. The subjects were asked to complete several questionnaires during rest periods, which included demographic information, the Nordic safety climate questionnaire (NOSACQ-50), and the generic job stress questionnaire (GJSQ). Additionally, data on the frequency and intensity of accidents among participants were gathered from the health unit of the company. Path analysis was conducted by structural equation modeling (SEM) in Analysis of Moment Structures (AMOS) software. Results: The results revealed that the latent variable of safety climate with an effect coefficient of – 0.112 did not have a direct effect on accident risk (P = 0.343). However, safety climate with an effect coefficient of − 0.633 had an indirect effect on accident risk through job stress (P < 0.001). The total score of job stress had a significant direct effect (0.649) on accident risk (P < 0.001). Among the dimensions of safety climate, the variables of management’s safety priority, commitment, and competence (− 0.108) and workers’ safety commitment (− 0.107) had the highest indirect effect coefficients on accident risk. Among the dimensions of job stress, the highest indirect effects belonged to the variables of conflict at work (0.636), physical environment (0.631), and workload and responsibility (0.631), respectively. Conclusion: The results of the study revealed that job stress mediates the relationship between safety climate and accident risk. This finding suggests that organizations can potentially decrease accidents in industries by addressing and managing job stress in the workplac
Long non-coding RNAs and gastric cancer: An update of potential biomarkers and therapeutic applications
No full textThe frequent metastasis of gastric cancer (GC) complicates the cure and therefore the development of effective diagnostic and therapeutic approaches is urgently necessary. In recent years, lncRNA has emerged as a drug target in the treatment of GC, particularly in the areas of cancer immunity, cancer metabolism, and cancer metastasis. This has led to the demonstration of the importance of these RNAs as prognostic, diagnostic and therapeutic agents. In this review, we provide an overview of the biological activities of lncRNAs in GC development and update the latest pathological activities, prognostic and diagnostic strategies, and therapeutic options for GC-related lncRNAs
The effect of infusion time on Echium amoenum extract -induced hepatotoxicity in vitro
No full textEchium amoenum is an annual herb native to the northern mountains of Iran which has medicinal application. Petals of Echium amoenum (Gole-Gavzaban) is one of the most valuable medicinal plants in Iranian folk medicine. The dry petals of E. amoenum have long been used as a sedative, tonic, anxiolytic and as a treatment for sore throat, cough and inflammation. Previous studies have shown that petals of E. amoenum contain four toxic pyrrolizidine alkaloids but conflicting results have been acquired in experimental studies investigating the hepatotoxicy of E. amoenum. However, the direct effect of E. amoenum on liver cells and the complete mechanisms of its possible cytotoxic effects toward these cells remain to be defined. The main aim of this study was to assay the mechanisms underlying the toxic effects of E. amoenum toward hepG2 cells. E. amoenum extract was obtained by infusion of dried petals in hot water (90 centigrade) for 15 or 30 min. Cell viability and mechanistic parameters were determined following 12 h incubation of hepG2 with E. amoenum extract that was obtained after 15 or 30 min infusion. The results indicated that E. amoenum extract exerts cytotoxic effects on hepG2 cells, probably through mitochondrial and lysosomal damage induced by glutathione depletion and oxidative stress