Pelvic Pain, Mental Health and Quality of Life in Adolescents with Endometriosis after Surgery and Dienogest Treatment.

BACKGROUND: Diagnostic and treatment delays have caused significant impacts on the physical and emotional well-being of adolescents with endometriosis, though such research is limited. This study aimed to assess the effects of one-year dienogest therapy on the clinical picture, pain patterns, psycho-emotional status, and quality-of-life indicators in adolescents with endometriosis after surgical treatment. METHODS: The study enrolled 32 girls aged 13-17 with peritoneal endometriosis to analyze one-year dynamics of the Visual Analog Scale (VAS), McGill Pain Questionnaire, Beck Depression Scale (BDI), Hospital Anxiety and Depression Scale (HADS), Spielberger State-Trait Anxiety Inventory (STAI) and SF-36 quality-of-life survey scores along with clinical and laboratory indicators before surgery and after one-year dienogest therapy. RESULTS: The therapy provided a significant alleviation of endometriosis-associated clinical symptoms, including dysmenorrhea, pelvic pain, gastrointestinal/dysuria symptoms, decreased everyday activity (<0.001), a decrease in anxiety/depression scores (BDI, HADS, STAI), and quality-of-life improvement (<0.001). These effects were accompanied by beneficial dynamics in hormone and inflammatory markers (prolactin, cortisol, testosterone, estradiol, CA-125, neutrophil/lymphocyte ratio; <0.005) within reference ranges. A low body mass index and high C-reactive protein levels were associated with higher VAS scores; a high estradiol level was a factor for anxiety/depression aggravation (<0.05). CONCLUSIONS: Dienogest, after surgical treatment, significantly improved quality of life and reduced pain symptoms while showing good tolerability and compliance, and reasoning with timely hormonal therapy in adolescents with endometriosis.

Moderating Role of Self-Compassion in the Relationships Between the Three Forms of Perfectionism with Anger, Aggression, and Hostility.

The prevalence of aggression in adolescents is on the rise, and it could be a serious public health concern. Studies have found positive relationships between perfectionism with anger, aggression, and hostility. However, the moderating role of self-compassion in the links between perfectionism with anger, aggression, and hostility has not been studied. To better understand the relationships between the three forms of perfectionism with anger, aggression, and hostility, this study aimed to explore the moderating role of self-compassion. Participants were 380 undergraduates selected using a multi-stage cluster sampling technique from three universities in Iran. Participants completed the Self-Compassion Scale, the Multidimensional Perfectionism Scale, and the Aggression Questionnaire Scale. The results from structural equation modelling analysis showed that other-oriented perfectionism and socially prescribed perfectionism positively predicted anger, aggression, and hostility. The results showed that self-oriented perfectionism significantly and positively predicted anger and hostility; but there were no observed statistically significant relationships of self-oriented perfectionism with verbal aggression and physical aggression. The findings showed that self-compassion played a moderating role in the relationships between other-oriented perfectionism and socially prescribed perfectionism with anger, aggression, and hostility; however, it did not play a moderating effect on self-oriented perfectionism with anger, aggression, and hostility. The findings provide a deeper understanding of the moderating role of self-compassion in the links between other-oriented perfectionism and socially prescribed perfectionism with anger, aggression, and hostility among undergraduates. The findings of this study could be applicable for psychologists and counselors who deal with aggressive behavior, anger, and hostility in undergraduate students to assess the three forms of perfectionism and self-compassion.

Emerging role of human microbiome in cancer development and response to therapy: special focus on intestinal microflora.

In recent years, there has been a greater emphasis on the impact of microbial populations inhabiting the gastrointestinal tract on human health and disease. According to the involvement of microbiota in modulating physiological processes (such as immune system development, vitamins synthesis, pathogen displacement, and nutrient uptake), any alteration in its composition and diversity (i.e., dysbiosis) has been linked to a variety of pathologies, including cancer. In this bidirectional relationship, colonization with various bacterial species is correlated with a reduced or elevated risk of certain cancers. Notably, the gut microflora could potentially play a direct or indirect role in tumor initiation and progression by inducing chronic inflammation and producing toxins and metabolites. Therefore, identifying the bacterial species involved and their mechanism of action could be beneficial in preventing the onset of tumors or controlling their advancement. Likewise, the microbial community affects anti-cancer approaches' therapeutic potential and adverse effects (such as immunotherapy and chemotherapy). Hence, their efficiency should be evaluated in the context of the microbiome, underlining the importance of personalized medicine. In this review, we summarized the evidence revealing the microbiota's involvement in cancer and its mechanism. We also delineated how microbiota could predict colon carcinoma development or response to current treatments to improve clinical outcomes.

CRISPR/Cas9 application in cancer therapy: a pioneering genome editing tool.

The progress of genetic engineering in the 1970s brought about a paradigm shift in genome editing technology. The clustered regularly interspaced short palindromic repeats/CRISPR associated protein 9 (CRISPR/Cas9) system is a flexible means to target and modify particular DNA sequences in the genome. Several applications of CRISPR/Cas9 are presently being studied in cancer biology and oncology to provide vigorous site-specific gene editing to enhance its biological and clinical uses. CRISPR's flexibility and ease of use have enabled the prompt achievement of almost any preferred alteration with greater efficiency and lower cost than preceding modalities. Also, CRISPR/Cas9 technology has recently been applied to improve the safety and efficacy of chimeric antigen receptor (CAR)-T cell therapies and defeat tumor cell resistance to conventional treatments such as chemotherapy and radiotherapy. The current review summarizes the application of CRISPR/Cas9 in cancer therapy. We also discuss the present obstacles and contemplate future possibilities in this context.

Optimizing sgRNA to Improve CRISPR/Cas9 Knockout Efficiency: Special Focus on Human and Animal Cell.

During recent years, clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated protein 9 (Cas9) technologies have been noticed as a rapidly evolving tool to deliver a possibility for modifying target sequence expression and function. The CRISPR/Cas9 tool is currently being used to treat a myriad of human disorders, ranging from genetic diseases and infections to cancers. Preliminary reports have shown that CRISPR technology could result in valued consequences for the treatment of Duchenne muscular dystrophy (DMD), cystic fibrosis (CF), ß-thalassemia, Huntington's diseases (HD), etc. Nonetheless, high rates of off-target effects may hinder its application in clinics. Thereby, recent studies have focused on the finding of the novel strategies to ameliorate these off-target effects and thereby lead to a high rate of fidelity and accuracy in human, animals, prokaryotes, and also plants. Meanwhile, there is clear evidence indicating that the design of the specific sgRNA with high efficiency is of paramount importance. Correspondingly, elucidation of the principal parameters that contributed to determining the sgRNA efficiencies is a prerequisite. Herein, we will deliver an overview regarding the therapeutic application of CRISPR technology to treat human disorders. More importantly, we will discuss the potent influential parameters (e.g., sgRNA structure and feature) implicated in affecting the sgRNA efficacy in CRISPR/Cas9 technology, with special concentration on human and animal studies.

A deep insight into CRISPR/Cas9 application in CAR-T cell-based tumor immunotherapies.

To date, two chimeric antigen receptors (CAR)-T cell products from autologous T cells have been approved by The United States Food and Drug Administration (FDA). The case-by-case autologous T cell generation setting is largely considered as a pivotal restraining cause for its large-scale clinical use because of the costly and prolonged manufacturing procedure. Further, activated CAR-T cells mainly express immune checkpoint molecules, including CTLA4, PD1, LAG3, abrogating CAR-T anti-tumor activity. In addition, CAR-T cell therapy potently results in some toxicity, such as cytokine releases syndrome (CRS). Therefore, the development of the universal allogeneic T cells with higher anti-tumor effects is of paramount importance. Thus, genome-editing technologies, in particular, clustered regularly interspaced short palindromic repeat (CRISPR)-Cas9 are currently being used to establish "off-the-shelf" CAR-T cells with robust resistance to immune cell-suppressive molecules. In fact, that simultaneous ablation of PD-1, T cell receptor alpha constant (TRAC or TCR), and also ß-2 microglobulin (B2M) by CRISPR-Cas9 technique can support the manufacture of universal CAR-T cells with robust resistance to PD-L1. . Indeed, the ablation of ß2M or TARC can severely hinder swift elimination of allogeneic T cells those express foreign HLA-I molecules, and thereby enables the generation of CAR-T cells from allogeneic healthy donors T cells with higher persistence in vivo. Herein, we will deliver a brief overview of the CAR-T cell application in the context of tumor immunotherapy. More importantly, we will discuss recent finding concerning the application of genome editing technologies for preparing universal CAR-T cells or cells that can effectively counter tumor escape, with a special focus on CRISPR-Cas9 technology.

Interleukin-25: New perspective and state-of-the-art in cancer prognosis and treatment approaches.

Cancer is a leading cause of death which imposes a substantial financial burden. Among the several mechanisms involved in cancer progression, imbalance of immune cell-derived factors such as cytokines and chemokines plays a central role. IL-25, as a member of the IL-17 cytokine subfamily, exerts a paradoxical role in cancer, including tumor supportive and tumor suppressive. Hence, we have tried to clarify the role of IL-25 and its receptor in tumor progression and cancer prognosis. It has been confirmed that IL-25 exerts a tumor-suppressive role through inducing infiltration of eosinophils and B cells into the tumor microenvironment and activating the apoptotic pathways. In contrast, the tumor-supportive function has been implemented by activating inflammatory cascades, promoting cell cycle, and inducing type-2 immune responses. Since IL-25 has been dysregulated in tumor tissues and this dysregulation is involved in cancer development, its examination can be used as a tumor diagnostic and prognostic biomarker. Moreover, IL-25-based therapeutic approaches have shown promising results in cancer inhibition. In cancers in which IL-25 has a tumor-suppressive function, employing IL-25-enhancing approaches, such as Virulizin® and dihydrobenzofuran administration, has potentially inhibited tumor cell growth. On the other hand, in the case of IL-25-dependent tumor progression, using IL-25 blocking methods, including anti-IL-25 antibodies, might be a complementary approach to the other anticancer agent. Collectively, it is hoped, IL-25 might be a promising target in cancer treatment.

Mortality Rate Due to Circulatory and Alcohol-Dependent Diseases in Different Climatic Zones of Russia.

AIM: Evaluation of the impact of climatic factors on the formation of mortality due to circulatory diseases and a group of diseases related to alcohol consumption identified as alcohol-dependent. METHODS: The study subject was the adult population residing in different climatic zones of Russia: in the second, third and fourth zones, with different conditions: average annual temperature (5.2°C; 1-2°C; -2.0°C), snow cover duration (≤ 150 days, ≤ 180 days, ≈ 220 days) sunshine duration and the presence of polar night and polar day in the territory of the fourth climatic zone. The assessment "impact-case of death" was carried out by calculating the standardized incidence ratio (SIR) with 95% confidence intervals (CI) for circulatory system diseases (CSD) and alcohol-dependent diseases (ADD) in accordance with the international classification of diseases (ICD-X). RESULTS: The SIR of death from alcohol-dependent diseases for the female population in the 4th climatic zone (Murmansk Region) was the highest: the SIR of death from ADD 1.87; 95% CI (1.5-2.7), the SIR of death from CSD 1.3; 95% CI (1.2-2.3). For the female population in the 3rd climatic zone (Novosibirsk Region), the SIR of death has amounted to: SIRADD 1.52; 95% CI (1.2-1.87), SIRCSD 1.14; 95 CI (1.01-1.3). Living in the 3rd climatic zone was not so important for the health of the male population: the SIR of death from CSD 1.1; 95% CI (1.05-1.13); the SIR of death from ADD 0.8; 95% CI (0.65-0.98). However, living in the 4th climatic zone (Murmansk Region) poses a higher risk of death for the male population: SIRCSD 1.22 (22.0%); 95% CI (1.02-3.95); SIRADD 1.45 (45.0%); 95% CI (0.98-2.1). CONCLUSION: Living in high northern latitudes contributes to higher levels of mortality, both female and male, from circulatory and alcohol-dependent diseases.