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Cancers invoke various pathways to mitigate external and internal stresses to continue their growth and progression. We previously reported that the eIF2 kinase GCN2 and the integrated stress response are constitutively active in prostate cancer (PCa) and are required to maintain amino acid homeostasis needed to fuel tumor growth. However, although loss of GCN2 function reduces intracellular amino acid availability and PCa growth, there is no appreciable cell death. Here, we discovered that the loss of GCN2 in PCa induces prosenescent p53 signaling. This p53 activation occurred through GCN2 inhibition–dependent reductions in purine nucleotides that impaired ribosome biogenesis and, consequently, induced the impaired ribosome biogenesis checkpoint. p53 signaling induced cell cycle arrest and senescence that promoted the survival of GCN2-deficient PCa cells. Depletion of GCN2 combined with loss of p53 or pharmacological inhibition of de novo purine biosynthesis reduced proliferation and enhanced cell death in PCa cell lines, organoids, and xenograft models. Our findings highlight the coordinated interplay between GCN2 and p53 regulation during nutrient stress and provide insight into how they could be targeted in developing new therapeutic strategies for PCa. Editor's summary: The integrated stress response (ISR) enables tumor cells to adapt quickly to their tissue environment, thus supporting cell survival and tumor progression. Cordova et al. found that inhibiting the ISR kinase GCN2 kills prostate cancer cells deficient in the transcription factor p53. GCN2 inhibition decreased the availability of amino acids that are used in purine nucleotide synthesis. In turn, this nucleotide deficiency was survivable only with p53 signaling, which induced cell cycle arrest and senescence. In mice, although inhibiting GCN2 slowed the growth of p53-functional tumors, it did so to a greater extent and induced cell death in p53-deficient tumors. The loss of p53 typically makes killing tumor cells challenging, and these findings indicate a way to take advantage of those mutations. —Leslie K. Ferrarelli [ABSTRACT FROM AUTHOR]

Background and Aims: Hypovitaminosis D is involved in the development and progression of atherosclerosis, and it is more prevalent in women. The differential impact of hypovitaminosis D on the severity of coronary artery disease (CAD) between genders remains poorly understood. This study aims to address this literature gap. Methods: A total of 1484 consecutive patients with acute myocardial infarction (AMI) were enrolled in the study. Hypovitaminosis D was defined as vitamin D ≤ 20 ng/mL. CAD was defined as the presence of at least one coronary vessel stenosis > 50%, while severe CAD was defined as left main disease and/or three-vessel disease > 50%. Results: The mean age of the cohort was 66.3 (11.5) years, with a predominance of the male gender (71.8%). Vitamin D values were significantly lower in women than in men (15.7 [8.4–25.4] ng/mL vs. 17.9 [11–24.3] ng/mL, p = 0.01). A higher prevalence of severe CAD was observed in female patients with hypovitaminosis D compared to those without (33% vs. 19%, p < 0.01). This finding was not observed in men. Among women, hypovitaminosis D significantly increased the risk of severe CAD (OR: 1.85, p = 0.01), together with diabetes mellitus (DM) and older age, adjusted for GFR < 60 mL/min/1.73 m2, cholesterol and body mass index. Furthermore, women with both hypovitaminosis D and DM had more than three times the risk of severe CAD compared with women who lacked both (OR: 3.56, p = 0.02). Conclusions: In women, hypovitaminosis D increases the risk of severe CAD, and the co-existence of hypovitaminosis D and DM triples the incidence of severe CAD. [ABSTRACT FROM AUTHOR]

Background: Marital satisfaction is one of the important components of quality of life. Women's marital satisfaction is affected when they enter the middle age period, due to the mental and emotional tensions caused by the physical changes. In this regard, the present study aimed to investigate the association of quality of life with marital satisfaction, stress, and anxiety in middle-aged women referring to health centers of Ahvaz city, Iran. Methods: This cross-sectional descriptive-analytical study was conducted on 1,000 middle-aged married women (30-59 year of age) under the auspices of health centers of Ahvaz city, Iran in 2019. The subjects were selected by simple random sampling method, and were asked to complete demographic characteristics, quality of life questionnaire, Enrich marital satisfaction questionnaire, Holmes-Raheh stress questionnaire, and Spielberger state-trait anxiety inventory. The data were analyzed by using SPSS 0.22 software through mean, standard deviation, frequency, Pearson correlation and regression (p = 0.05). Results: Based on the results, 42.4% of the participants were between 40 and 50 years of age, 35.6% had a high school diploma, and 50% of them were housewives. Also, the results of Pearson's correlation showed a positive and significant relationship between quality of life and marital satisfaction (r = 0.178) (p < 0.001). However, quality of life had a negative and significant relationship with anxiety (r = -0.552) (r < 0.001) and stress (r = -0.188) (p < 0.001). Conclusion: Given the positive and significant relationship between quality of life and marital satisfaction, appropriate trainings are highly recommended for couples to increase the quality of life and marital satisfaction of middle-aged women and thus strengthen the health of family and society. [ABSTRACT FROM AUTHOR]

Copyright of Balikesir Health Sciences Journal / Balıkesir Sağlık Bilimleri Dergisi is the property of Balikesir Health Sciences Journal (BAUN Health Sci J) and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

This study aims to assess the validity and reliability of the Turkish version of the FSFI-6 questionnaire,an abbreviated version of FSFI-19,a common tool for evaluating female sexual function. The study included 120 female patients aged between 18-65 years who presented to the urology clinic between December 2019 and March 2020. The Turkish version of FSFI-6 was translated from the English version for validation. The abridged FSFI-6 questionnaire consists of questions 2, 4, 7, 11, 16, and 17 of the FSFI-19 form. We recorded the demographic data of the patients. All subjects filled out the FSFI-19 and FSFI-6 questionnaires. The patients were asked to fill out the questionnaires again after two weeks. The mean age of the subjects was 46.58 ± 9.89 years (28-63). The results of the reliability analysis indicated that the intraclass correlation coefficient of the total FSFI-6 score was 0.92 (weighted kappa coefficients of individual items, 0.868-0.975) and the Cronbach's alpha was 0.862. The validity analysis indicated that the mean total FSFI-6 score was strongly correlated with the mean FSFI-19 score (p < 0.001, r = 0.997). In the test-retest analysis,the kappa coefficient was calculated as 0.891. The FSFI-19 and FSFI-6 scores of the patients with (n = 52) and without climacturia (n = 68) were compared, and it was observed that the scores of the patients with climacturia were significantly lower than those without climacturia (p < 0.001). The abbreviated FSFI-6 questionnaire is a valuable tool for screening women with FSD. It can be used more extensively due to being short and easy to apply. Our results approve the Turkish version of the questionnaire as a valid and reliable tool for evaluating FSD., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

Depressive symptoms are a common menopausal feature in middle-aged women and are associated with dietary factors. This study aimed to determine the association between dietary patterns and depressive symptoms in 2190 Korean women aged 45–69 years. Depressive symptoms were screened using the Beck Depression Inventory-II (BDI-II), and food intake was examined using a food frequency questionnaire. Dietary patterns were derived from principal components analysis and identified two dietary patterns: a "healthy" dietary pattern (high intake of whole-grain rice, legumes, vegetables, fruits, and fish) and an "unhealthy" dietary pattern (high intake of noodles, dumplings, sweets, red meat, soda, and coffee). After adjusting for all confounding factors, those with the highest healthy dietary pattern scores had a 0.56-fold lower risk of depressive symptoms than those with the lowest score (Odds Ratio (OR) = 0.56, 95% confidence interval (CI): 0.37–0.84, p for trend = 0.006). Conversely, those with the highest unhealthy pattern scores had a 1.85-fold higher risk of depressive symptoms than that of those in the lowest quartile (OR = 1.85, 95% CI: 1.30–2.63, p for trend = 0.002). In middle-aged women, a dietary pattern of high intake of fiber-rich whole-grain rice, fruits, vegetables, and legumes may help prevent and manage depressive symptoms. [ABSTRACT FROM AUTHOR]

Purpose: PARP inhibitors have revolutionized the treatment landscape for advanced prostate cancer (PCa) patients who harboring mutations in homologous recombination repair (HRR) genes. However, the molecular mechanisms underlying PARP inhibitors function beyond DNA damage repair pathways remain elusive, and identifying novel predictive targets that favorably respond to PARP inhibitors in PCa is an active area of research. Methods: The expression of GSDME in PCa cell lines and human PCa samples was determined by western blotting. Targeted bisulfite sequencing, gene enrichment analysis (GSEA), clone formation, construction of the stably transfected cell lines, lactate dehydrogenase (LDH) assay, western blotting as well as a mouse model of subcutaneous xenografts were used to investigate the role of GSDME in PCa. The combinational therapeutic effect of olaparib and decitabine was determined using both in vitro and in vivo experiments. Results: We have found low expression of GSDME in PCa. Interestingly, we demonstrated that GSDME activity is robustly induced in olaparib-treated cells undergoing pyroptosis, and that high methylation of the GSDME promoter dampens its activity in PCa cells. Intriguingly, genetically overexpressing GSDME does not inhibit tumor cell proliferation but instead confers sensitivity to olaparib. Furthermore, pharmacological treatment with the combination of olaparib and decitabine synergistically induces GSDME expression and cleavage through caspase-3 activation, thus promoting pyroptosis and enhancing anti-tumor response, ultimately resulting in tumor remission. Conclusion: Our findings highlight a novel therapeutic strategy for enhancing the long-term response to olaparib beyond HRR-deficient tumors in PCa, underscoring the critical role of GSDME in regulating tumorigenesis. [ABSTRACT FROM AUTHOR]

Aberrant DNA methylation has been implicated as a key driver of prostate cancer lineage plasticity and histologic transformation to neuroendocrine prostate cancer (NEPC). DNA methyltransferases (DNMTs) are highly expressed, and global DNA methylation is dysregulated in NEPC. We identified that deletion of DNMT genes decreases expression of neuroendocrine lineage markers and substantially reduced NEPC tumor development and metastasis in vivo. Decitabine, a pan-DNMT inhibitor, attenuated tumor growth in NEPC patient–derived xenograft models, as well as retinoblastoma gene (RB1)–deficient castration-resistant prostate adenocarcinoma (CRPC) models compared with RB1-proficient CRPC. We further found that DNMT inhibition increased expression of B7 homolog 3 (B7-H3), an emerging druggable target, via demethylation of B7-H3. We tested DS-7300a (i-DXd), an antibody-drug conjugate targeting B7-H3, alone and in combination with decitabine in models of advanced prostate cancer. There was potent single-agent antitumor activity of DS-7300a in both CRPC and NEPC bearing high expression of B7-H3. In B7-H3–low models, combination therapy of decitabine plus DS-7300a resulted in enhanced response. DNMT inhibition may therefore be a promising therapeutic target for NEPC and RB1-deficient CRPC and may sensitize B7-H3–low prostate cancer to DS-7300a through increasing target expression. NEPC and RB1-deficient CRPC represent prostate cancer subgroups with poor prognosis, and the development of biomarker-driven therapeutic strategies for these populations may ultimately help improve patient outcomes. Editor's summary: DNA methyltransferases (DNMTs) are increased in neuroendocrine prostate cancer (NEPC), an aggressive cancer associated with frequent metastases and poor clinical outcomes. Here, Yamada and colleagues deleted DNMT genes in NEPC, leading to reduced tumor development and metastases in mice. The DNMT inhibitor decitabine also attenuated tumor growth in NEPC and RB1-deficient castration-resistant prostate adenocarcinoma (CRPC) preclinical models. Because decitabine treatment increased expression of B7 homolog 3 (B7-H3), the authors combined decitabine treatment with DS-7300a, an antibody-drug conjugate that specifically targets B7-H3, in B7-H3–low prostate cancers, leading to a synergistic response. These findings suggest decitabine as a treatment for NEPC. Further, they suggest that the combination of decitabine with DS-7300a could potentially improve treatment response in those with B7-H3–low tumors. —Melissa L. Norton [ABSTRACT FROM AUTHOR]

Herbal medicines are becoming increasingly popular among patients because they are well tolerated and do not exert severe side effects. Nevertheless, they receive little consideration in therapeutic settings. The present article reviews the current state of research on the clinical benefits of herbal medicines on five indication groups, psychosomatic disorders, gynecological complaints, gastrointestinal disorders, urinary and upper respiratory tract infections. The study search was based on the database PubMed and concentrated on herbal medicines legally approved in Europe. After applying defined inclusion and exclusion criteria, 141 articles were selected: 59 for psychosomatic disorders (100% randomized controlled trials; RCTs), 20 for gynecological complaints (56% RCTs), 19 for gastrointestinal disorders (68% RCTs), 16 for urinary tract infections (UTI, 63% RCTs) and 24 for upper respiratory tract infections (URTI) (79% RCTs). For the majority of the studies, therapeutic benefits were evaluated by patient reported outcome measures (PROs). For psychosomatic disorders, gynecological complaints and URTI more than 80% of the study outcomes were positive, whereas the clinical benefit of herbal medicines for the treatment of UTI and gastrointestinal disorders was lower with 55%. The critical appraisal of the articles shows that there is a lack of high-quality studies and, with regard to gastrointestinal disorders, the clinical benefits of herbal medicines as a stand-alone form of therapy are unclear. According to the current state of knowledge, scientific evidence has still to be improved to allow integration of herbal medicines into guidelines and standard treatment regimens for the indications reviewed here. In addition to clinical data, real world data and outcome measures can add significant value to pave the way for herbal medicines into future therapeutic applications. [ABSTRACT FROM AUTHOR]

Background: C-peptide is considered a peptide with active function in the body, which can affect people's health. However, the results of previous studies on the possible association of C-peptide with the risk of cardiometabolic disorders have not been fully understood. This systematic review and meta-analysis aimed to investigate the association between serum C-peptide level and the risk of cardiovascular disease (CVD) events. Methods: The various important databases, including PubMed, Scopus, and Web of Science, were searched comprehensively to November 2022 to identify the relevant studies. The HR(95% CI) or OR(95% CI) for observational studies were extracted and converted into log HR or log OR and their standard deviation(SD) was computed. A random-effects model with an inverse variance weighting method was conducted, to calculate the pooled effect size. Results: Sixteen observational studies, including one case-control study, eight cohort studies, and seven cross-sectional studies were included in the current meta-analysis. The sample size ranged from 90 to 7030, with an age range from 12 to 85 years. During the follow-up time (ranging from 5 to 17 years), 4852 CVD events occurred. Based on cohort and case-control studies, the pooled results showed no significant association between serum C-peptide with CVD events risk (RR = 1.02;95%CI:0.91–1.15, I2 = 34.7%; P-heterogeneity = 0.140). For cross-sectional studies, the pooled results indicated a positive association between serum C-peptide and the odds of CVD outcomes (OR = 1.35;95%CI:1.04–1.76, I2 = 83.6%; P-heterogeneity < 0.001). Conclusions: The pooled results of the current study suggested that C-peptide level was not related to the risk of CVD events in cohort studies, however, the meta-analysis of cross-sectional studies showed a significant association between C-peptide and an increased risk of CVD events. [ABSTRACT FROM AUTHOR]

Gastric carcinoma high expressed transcript 1 (GHET1) is an oncogenic Long noncoding RNA. GHET1 expression promotes multiple levels of developing a complex molecular network. The main purpose of the study was to investigate the mechanism by which long noncoding RNA (lncRNA) GHET1 promotes prostate cancer cell proliferation and related metabolism. In vitro study, lncRNA GHET1 was overexpressed in LN‐cap, PC‐3, 22RV1, and C4‐2 cells. The cell viability was measured by MTT and trans‐well assay. A flow cytometer was also used to detect cell cycles and apoptosis. Western blot analysis was used for protein expression validation. mRNA expression was detected by real‐time PCR. lncRNA GHET1 enhanced cell proliferation, migration, and could resist paclitaxel‐induced apoptosis and cell cycle arrest GHET1 expression stimulates reactive oxygen species (ROS) level upregulated in prostate cancer cells, increased the expression of HIFα, IL‐1B and IL‐6, and activated ROS/STAT‐3/Twsit1 signaling pathway. Knockdown GHET1 could reduce cell proliferation and migration due to the overexpression of GHET1. lncRNA GHET1 promotes prostate cancer growth through oxidative stress signaling pathways and resists the antineoplastic drug paclitaxel, which can be used as a target for antineoplastic therapy and drug resistance therapy in the future in clinics. [ABSTRACT FROM AUTHOR]

The optimal intensity of physical activity for alleviating depression in middle-aged and older adults remains unclear. The World Health Organization (WHO) physical activity guidelines recommend adults and older adults to accumulate at least 150–300 minutes of moderate or 75–150 minutes of vigorous aerobic-type physical activity weekly or an equivalent combination of both for health benefits including reduced risk of depression. This parallel, assessor-blinded, pilot randomized controlled trial preliminarily compared the effectiveness of the minimal volume of aerobic-type physical activity at different intensities as recommended by WHO (150 minutes of moderate walking exercise and 75 minutes of vigorous walking exercise weekly) on alleviating depression in middle-aged and older adults. Thirty-five participants were randomized to the control group (CON), moderate walking exercise group (MOD), or vigorous walking exercise group (VIG). The exercise frequency was three times a week and the intervention duration was 12 weeks. The primary outcome was the severity of depression assessed by Beck Depression Inventory. Secondary outcomes included severity of anxiety, sleep quality, quality of life, and cardiorespiratory fitness. Thirty participants completed the study (CON: n = 10, MOD: n = 10, VIG: n = 10). Participants in both MOD and VIG had significantly decreased depression severity after the intervention compared to CON (both p < 0.001). There was no significant difference between MOD and VIG (p = 0.92). Both MOD and VIG interventions also mitigated anxiety severity, improved quality of life and cardiorespiratory fitness. The minimum volume of walking exercise at either moderate or vigorous intensity was found to alleviate depression in middle-aged and older adults. Trial registration: ClinicalTrials.gov identifier: NCT04403373. Highlights The 12-week 150-minute moderate walking exercise and 75-minute vigorous walking exercise (the minimal weekly volumes of aerobic-type physical activity recommended by WHO guidelines) similarly reduced the severity of depression in middle-aged and older adults. The 12-week walking exercise interventions significantly reduced anxiety severity concomitant with improved quality of life and cardiorespiratory fitness in middle-aged and older adults with depression. [ABSTRACT FROM AUTHOR]

Checkpoint immunotherapy has yielded meaningful responses across many cancers but has shown modest efficacy in advanced prostate cancer. B7 homolog 3 protein (B7-H3/CD276) is an immune checkpoint molecule and has emerged as a promising therapeutic target. However, much remains to be understood regarding B7-H3's role in cancer progression, predictive biomarkers for B7-H3–targeted therapy, and combinatorial strategies. Our multi-omics analyses identified B7-H3 as one of the most abundant immune checkpoints in prostate tumors containing PTEN and TP53 genetic inactivation. Here, we sought in vivo genetic evidence for, and mechanistic understanding of, the role of B7-H3 in PTEN/TP53-deficient prostate cancer. We found that loss of PTEN and TP53 induced B7-H3 expression by activating transcriptional factor Sp1. Prostate-specific deletion of Cd276 resulted in delayed tumor progression and reversed the suppression of tumor-infiltrating T cells and NK cells in Pten/Trp53 genetically engineered mouse models. Furthermore, we tested the efficacy of the B7-H3 inhibitor in preclinical models of castration-resistant prostate cancer (CRPC). We demonstrated that enriched regulatory T cells and elevated programmed cell death ligand 1 (PD-L1) in myeloid cells hinder the therapeutic efficacy of B7-H3 inhibition in prostate tumors. Last, we showed that B7-H3 inhibition combined with blockade of PD-L1 or cytotoxic T lymphocyte–associated protein 4 (CTLA-4) achieved durable antitumor effects and had curative potential in a PTEN/TP53-deficient CRPC model. Given that B7-H3–targeted therapies have been evaluated in early clinical trials, our studies provide insights into the potential of biomarker-driven combinatorial immunotherapy targeting B7-H3 in prostate cancer, among other malignancies. Combinations to crush castration-resistant prostate cancer: Standard of care for prostate cancer includes androgen deprivation therapy; however, many patients progress, leading to castration-resistant prostate cancer (CRPC). Studies have sought to evaluate immunotherapy as a potential treatment for CRPC but have had limited success. To overcome this, Shi et al. evaluated targeted therapy of immune checkpoint B7-H3 in preclinical mouse models of CRPC alone and in combination with the blockade of programmed cell death ligand 1 (PD-L1). They saw that combination treatment induced durable antitumor effects in PTEN/TP53-deficient mice and represents a potential therapy for genomically similar prostate cancer. —DH [ABSTRACT FROM AUTHOR]

Prostate cancers are largely unresponsive to immune checkpoint inhibitors (ICIs), and there is strong evidence that programmed death-ligand 1 (PD-L1) expression itself must be inhibited to activate antitumor immunity. Here, we report that neuropilin-2 (NRP2), which functions as a vascular endothelial growth factor (VEGF) receptor on tumor cells, is an attractive target to activate antitumor immunity in prostate cancer because VEGF-NRP2 signaling sustains PD-L1 expression. NRP2 depletion increased T cell activation in vitro. In a syngeneic model of prostate cancer that is resistant to ICI, inhibition of the binding of VEGF to NRP2 using a mouse-specific anti-NRP2 monoclonal antibody (mAb) resulted in necrosis and tumor regression compared with both an anti–PD-L1 mAb and control immunoglobulin G. This therapy also decreased tumor PD-L1 expression and increased immune cell infiltration. We observed that the NRP2, VEGFA, and VEGFC genes are amplified in metastatic castration-resistant and neuroendocrine prostate cancer. We also found that individuals with NRP2High PD-L1High metastatic tumors had lower androgen receptor expression and higher neuroendocrine prostate cancer scores than other individuals with prostate cancer. In organoids derived from patients with neuroendocrine prostate cancer, therapeutic inhibition of VEGF binding to NRP2 using a high-affinity humanized mAb suitable for clinical use also diminished PD-L1 expression and caused a substantial increase in immune-mediated tumor cell killing, consistent with the animal studies. These findings provide justification for the initiation of clinical trials using this function-blocking NRP2 mAb in prostate cancer, especially for patients with aggressive disease. Preventing PD-L1 expression in prostate cancer: Unlike other solid tumors, prostate cancers do not respond particularly well to immune checkpoint inhibitors such as PD-L1 blockade. Thus, additional strategies are needed to promote antitumor immune responses. Here, Wang et al. demonstrated that antibody-mediated blockade of the interaction between vascular endothelial growth factor (VEGF) and neuropilin-2 (NRP2) reduced PD-L1 expression in prostate cancer and drove antitumor immune responses in mice. When the authors investigated patient samples, they found that those with more aggressive types of prostate cancer had higher expression of the genes encoding PD-L1 and NRP2, suggesting that this therapeutic axis may be especially valuable for these patients. —CM [ABSTRACT FROM AUTHOR]

There are many immediate and longer-term physical, psychological and metabolic benefits of being active during adolescence. These benefits exist when exercise and physical activity are undertaken in a state of energy balance. When exercise occurs in an environment of low energy availability, this is currently termed relative energy deficiency in sport and there are potential significant negative effects on mental well-being, bone, endocrine and metabolic health. Therefore, relative energy deficiency in sport may present to many different specialists or allied health professionals depending upon the symptoms or reasons for seeking help, which include injury, such as bone stress or soft tissue problems, irregular or absent menstruation, stress, anxiety or low mood, or sporting underperformance as examples. The promotion of physical activity in adolescence is a critical part of public health strategy. In parallel with this positive public health message, there needs to be an increase in the awareness of, and education about, relative energy deficiency in sport for those working with and looking after adolescents.This review provides an up to date, practical evidenced based guide on the recognition, investigation and management of relative energy deficiency in sport in the adolescent, both male and female. [ABSTRACT FROM AUTHOR]

Background. Metformin is one of the most common drugs for type 2 diabetes mellitus (T2DM) treatment. In addition, metformin intends to have a positive effect on the prognosis of several cancers. However, the therapeutic effect of metformin on gastric cancer (GC) remains controversial. This study explores and updates the therapeutic effect of metformin in GC patients with T2DM. Methods. We searched through PubMed, Embase, Web of Science, and the Cochrane Library for relevant articles by July 2022. The relationship between metformin therapy and the prognosis of GC patients with T2DM was evaluated based on the hazard ratio (HR) at a 95% confidence interval (95% CI). Overall survival (OS), cancer-specific survival (CSS), and progression-free survival (PFS) were the primary outcomes analyzed. Results. Seven retrospective cohort studies with a combined 2,858 patients met the inclusion criteria. OS and CSS were reported in six studies, and PFS was reported in four studies. Pooled results showed that, compared to the nonmetformin group, the prolonged OS (HR = 0.72, p = 0.001), CSS (HR = 0.81, p = 0.001), and PFS (HR = 0.70, p = 0.008) of the experimental group may be associated with the exposure to metformin. Conclusion. Metformin may have a beneficial effect on the prognosis of GC patients with T2DM. [ABSTRACT FROM AUTHOR]

Hormonal fluctuations, excessive clothing covering, sunscreen use, changes in body fat composition, a vitamin D-deficient diet, and a sedentary lifestyle can all predispose postmenopausal women to vitamin D deficiency. An effective supplementation plan requires a thorough understanding of underlying factors to achieve the desired therapeutic concentrations. The objective of this study was to conduct a systematic review of the predictors that affect vitamin D status in postmenopausal women. From inception to October 2022, we searched MEDLINE, Embase, Web of Science, Scopus, and clinical trial registries. Randomized clinical trials of postmenopausal women taking supplements of vitamin D with serum 25-hydroxyvitamin D (25(OH)D) measurement as the trial outcome were included. Two independent reviewers screened selected studies for full-text review. The final assessment covered 19 trials within 13 nations with participants aged 51 to 78. Vitamin D supplementation from dietary and pharmaceutical sources significantly increased serum 25(OH)D to optimal levels. Lower baseline serum 25(OH)D, lighter skin color, longer treatment duration, and prolonged skin exposure were all associated with a better response to vitamin D supplementation in postmenopausal women. [ABSTRACT FROM AUTHOR]

Early tumor diagnosis could reliably predict the behavior of tumors and significantly reduce their mortality. Due to the response to early cancerous changes at the molecular or cellular level, tumor biomarkers, including small molecules, proteins, nucleic acids, exosomes, and circulating tumor cells, have been employed as powerful tools for early cancer diagnosis. Therefore, exploring new approaches to detect tumor biomarkers has attracted a great deal of research interest. Lanthanide upconversion nanoparticles (UCNPs) provide numerous opportunities for bioanalytical applications. When excited by low-energy near-infrared light, UCNPs exhibit several unique properties, such as large anti-Stoke shifts, sharp emission lines, long luminescence lifetimes, resistance to photobleaching, and the absence of autofluorescence. Based on these excellent properties, UCNPs have demonstrated great sensitivity and selectivity in detecting tumor biomarkers. In this review, an overview of recent advances in tumor biomarker detection using UCNPs has been presented. The key aspects of this review include detection mechanisms, applications in vitro and in vivo, challenges, and perspectives of UCNP-based tumor biomarker detection. [ABSTRACT FROM AUTHOR]

Background. Prevention and timely treatment of gestational diabetes mellitus (GDM) are important to the prognosis of pregnant women and neonates. We aimed to conduct a meta-analysis to evaluate the effects and safety of vitamin D supplementation on GDM patients and neonates, to provide insights into clinical GDM treatment. Methods. Two authors searched the Medline, PubMed, Cochrane Library, Web of Science, Embase, CNKI, and Wanfang databases for randomized controlled trials (RCTs) on the effects and safety of vitamin D supplementation in GDM patients. The quality of the included RCTs was evaluated according to Cochrane handbook. RevMan 5.3 software was used for statistical analysis. Results. A total of 20 RCTs involving 1682 GDM patients were finally included, of whom 837 received vitamin D supplementation. Vitamin D supplementation in GDM patients increased the serum 25(OH)D level (SMD = 4.07, 95% CI: (2.73, 5.41)) and HDL level (SMD = 0.41, 95% CI: (0.23, 0.58)) and reduced serum LDL (SMD = −0.49, 95% CI: (−0.68, −0.29)), TG (SMD = −0.59, 95% CI: (−1.01, −0.17)), and TC (SMD = −0.67, 95% CI: (−1.19, −0.14)) levels in GDM patients (all P < 0.05). Besides, vitamin D supplementation reduced the risk of premature birth (OR = 0.37, 95% CI: (0.22, 0.62)), hyperbilirubinemia (OR = 0.38, 95% CI: (0.25, 0.58)), and neonatal hospitalization (OR = 0.38, 95% CI: (0.25, 0.58)) of neonates (all P < 0.05). No significant publication bias in synthesized results was found (all P > 0.05). Conclusions. Vitamin D supplementation improves the blood lipid level in GDM patients and reduces adverse neonatal outcomes. The dose and duration of vitamin D supplementation for safety need to be further investigated in future high-quality studies. [ABSTRACT FROM AUTHOR]

Some cardiovascular and respiratory diseases are triggered by changes in ambient temperature or extremes of temperature. This study aimed to clarify the changes in mortality associated with temperature-sensitive diseases in Japan during the COVID-19 pandemic. We used data from three major cities (Sapporo City, Tokyo 23 wards, and Osaka City) from 2010 to 2019 to determine disease mortality rates and monthly mean temperatures from April to December. If the pandemic had not occurred in 2020, the results showed that temperature-sensitive disease death counts would have increased from 324 to 980, based on a 95% confidence interval estimated from the past 10 years in Sapporo (19–56% increase in actual deaths from 2020), from 651 to 2,653 in Tokyo (10–39% increase), and from 235 to 1,343 in Osaka (8–48% increase). Analyses of meshed population data during the COVID-19 pandemic indicated that inhibiting people's behaviour and outdoor mobility, especially in older men, caused a decrease in mortality. [ABSTRACT FROM AUTHOR]

Failure of second-generation tyrosine kinase inhibitors (2GTKI) is a challenging situation in patients with chronic myeloid leukemia (CML). Asciminib, recently approved by the US Federal Drug Administration, has demonstrated in clinical trials a good efficacy and safety profile after failure of 2GTKI. However, no study has specifically addressed response rates to asciminib in ponatinib pretreated patients (PPT). Here, we present data on responses to asciminib from 52 patients in clinical practice, 20 of them (38%) with prior ponatinib exposure. We analyzed retrospectively responses and toxicities under asciminib and compared results between PPT and non-PPT patients.After a median follow-up of 30 months, 34 patients (65%) switched to asciminib due to intolerance and 18 (35%) due to resistance to prior TKIs. Forty-six patients (88%) had received at least 3 prior TKIs. Regarding responses, complete cytogenetic response was achieved or maintained in 74% and 53% for non-PPT and PPT patients, respectively. Deeper responses such as major molecular response and molecular response 4.5 were achieved in 65% and 19% in non-PPT versus 32% and 11% in PPT, respectively. Two patients (4%) harbored the T315I mutation, both PPT.In terms of toxicities, non-PPT displayed 22% grade 3-4 TEAE versus 20% in PPT. Four patients (20% of PPT) suffered from cross-intolerance with asciminib as they did under ponatinib.Our data supports asciminib as a promising alternative in resistant and intolerant non-PPT patients, as well as in intolerant PPT patients; the resistant PPT subset remains as a challenging group in need of further therapeutic options. [ABSTRACT FROM AUTHOR]

The coronavirus disease 2019 (COVID-19) pandemic has led to significant changes in life and healthcare all over the world. Pregnant women and their newborns require extra attention due to the increased risk of adverse outcomes. Adverse pregnancy outcomes include intensive care unit (ICU) admission, pulmonary, cardiac, and renal impairment leading to mortality. Immaturity and variations of the neonatal immune system may be advantageous in responding to the virus. Neonates are at risk of vertical transmission and in-utero infection. Impaired intrauterine growth, prematurity, vertical transmission, and neonatal ICU admission are the most concerning issues. Data on maternal and neonatal outcomes should be interpreted cautiously due to study designs, patient characteristics, clinical variables, the effects of variants, and vaccination beyond the pandemic. Cesarean section, immediate separation of mother-infant dyads, isolation of neonates, and avoidance of breast milk were performed to reduce transmission risk at the beginning of the pandemic in the era of insufficient knowledge. Vertical transmission was found to be low with favorable short-term outcomes. Serious fetal and neonatal outcomes are not expected, according to growing evidence. Long-term effects may be associated with fetal programming. Knowledge and lessons from COVID-19 will be helpful for the next pandemic if it occurs. IMPACT: Prenatal infection with SARS-CoV-2 is associated with adverse maternal and neonatal outcomes. Our review includes the effects of COVID-19 on the fetus and neonates, transmission routes, placental effects, fetal and neonatal outcomes, and long-term effects on neonates. There is a growing body of data and evidence about the COVID-19 pandemic. Knowledge and lessons from the pandemic will be helpful for the next pandemic if it happens., (© 2023. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

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Endometrial cancer (EC) kills about 76,000 women worldwide, with the highest incidence in industrialized countries. Because of the rise in disease mortality and new diagnoses, EC is now a top priority for women’s health. Serine racemase (SRR) is thought to play a role in the central nervous system, but its role in cancers, particularly in EC, is largely unknown. The current study starts with a pan-cancer examination of SRR’s expression and prognostic value before delving into SRR’s potential cancer-suppressing effect in patients with EC. SRR may affect the endometrial tumor immune microenvironment, according to subsequent immune-related analysis. SRR expression is also linked to several genes involved in specific pathways such as ferroptosis, N6-methyladenosine methylation, and DNA damage repair. Finally, we used the expression, correlation, and survival analyses to investigate the upstream potential regulatory non-coding RNAs of SRR. Overall, our findings highlight the prognostic significance of SRR in patients with EC, and we can formulate a reasonable hypothesis that SRR influences metabolism and obstructs key carcinogenic processes in EC. [ABSTRACT FROM AUTHOR]

Estradiol (E2) has been proven to be effective in treating perimenopausal depression (PD); however, the downstream signaling pathways have not been fully elucidated. Transient receptor potential channels 6 (TRPC6) plays a vital role in promoting neuronal development and the formation of excitatory synapses. At present, we found that the serum levels of E2 and brain-derived neurotrophic factor (BDNF) declined significantly in the women with PD compared to perimenopausal women, which was accompanied by a clear reduction in TRPC6 levels. To further reveal the effects of TRPC6 on neuronal survival and excitability, the PD-like rat model was established by the total removal of left ovary and 80% removal of right ovary followed by 21 days of the chronic unpredictable mild stress. Intragastric administration of E2 (2 mg/kg), intraperitoneal injection of BDNF/TrB signaling pathway inhibitor (K252a, 100 mg/kg) and TRPC6 agonist (OAG, 0.6 mg/kg), and intracerebroventricular infusion of anti-BDNF antibody for blocking BDNF (0.5 mg/24 ml/rat) daily for 21 days were conducted. The levels of BDNF and TRPC6 in rat serum were lower in PD rats compared to the control rats; the depressionlike behavior was induced, the neuronal death rate in the hippocampus increased, and the thickness of postsynaptic density (PSD) and the number of asymmetric synapses decreased significantly in the PD group. E2 treatment greatly upregulated the serum levels of BDNF and TRPC6, the neuronal excitability indicated by an elevation in the PSD thickness and the numbers of asymmetric synapses, and these actions were reversed by K252a; co-administration of TRPC6 agonist and K252a improved neuronal degeneration and increased the neuronal excitability induced in the E2-treated PD rats. K252a or anti-BDNF antibody inhibited the increased neuronal BDNF and TRPC6 expression in E2-treated PD rats; co-treatment of TRPC6 agonist and anti-BDNF antibody reduced neuronal death and increased the BDNF and TRPC6 expression in the hippocampal CA1 neurons in the E2-treated PD rats. These results suggest that the neuroprotective role of E2 in PD is closely related to enhance the activity of BDNF/TRPC6 pathway and is helpful to provide new prevention and strategies. [ABSTRACT FROM AUTHOR]

Insulin hormone is of great importance for many diseases, especially for diabetes management. Therefore, different detection strategies have been used for sensitive and fast detection of insulin in physiological conditions. In this study, an electrochemical signal switch aptasensor for sensitive detection of insulin has been developed based on methylene blue (MB)–modified insulin-specific aptamer immobilized on gold-deposited screen-printed electrodes. The aptamer fabrication parameters of aptamer, blocker and insulin incubation times, were optimized using the response surface method as 180 min, 60 min, and 25 min, respectively. Optimized values were then used to fabricate aptasensor, and analytical parameters were calculated using square wave voltammetry. The calibration of the aptasensor was performed based on the current difference calculated by subtracting the respective current values obtained for the MB-probe's on and off positions. The linear working range and limit of detection of the aptasensor were calculated as 25–150 pM and 18.5 pM, respectively. The relative standard error and accuracy of the aptasensor were 9.5% and 6.4%, respectively. The interference study showed no significant interfering substances except for uric acid, and the stability of the sensor was good for 10 days keeping 92% of its initial performance. The developed aptasensor showed promising results for easy and sensitive insulin detection in physiological conditions. [ABSTRACT FROM AUTHOR]

Progress in the field of insomnia since 2017 necessitated this update of the European Insomnia Guideline. Recommendations for the diagnostic procedure for insomnia and its comorbidities are: clinical interview (encompassing sleep and medical history); the use of sleep questionnaires and diaries (and physical examination and additional measures where indicated) (A). Actigraphy is not recommended for the routine evaluation of insomnia (C), but may be useful for differential-diagnostic purposes (A). Polysomnography should be used to evaluate other sleep disorders if suspected (i.e. periodic limb movement disorder, sleep-related breathing disorders, etc.), treatment-resistant insomnia (A) and for other indications (B). Cognitive-behavioural therapy for insomnia is recommended as the first-line treatment for chronic insomnia in adults of any age (including patients with comorbidities), either applied in-person or digitally (A). When cognitive-behavioural therapy for insomnia is not sufficiently effective, a pharmacological intervention can be offered (A). Benzodiazepines (A), benzodiazepine receptor agonists (A), daridorexant (A) and low-dose sedating antidepressants (B) can be used for the short-term treatment of insomnia (≤ 4 weeks). Longer-term treatment with these substances may be initiated in some cases, considering advantages and disadvantages (B). Orexin receptor antagonists can be used for periods of up to 3 months or longer in some cases (A). Prolonged-release melatonin can be used for up to 3 months in patients ≥ 55 years (B). Antihistaminergic drugs, antipsychotics, fast-release melatonin, ramelteon and phytotherapeutics are not recommended for insomnia treatment (A). Light therapy and exercise interventions may be useful as adjunct therapies to cognitive-behavioural therapy for insomnia (B)., (© 2023 The Authors. Journal of Sleep Research published by John Wiley & Sons Ltd on behalf of European Sleep Research Society.)