Metallothionein Alleviates Glutathione Depletion-Induced Oxidative Cardiomyopathy through CISD1-Dependent Regulation of Ferroptosis in Murine Hearts.

This study was designed to discern the effect of heavy scavenger metallothionein on glutathione (GSH) deprivation-evoked cardiac anomalies and mechanisms involved with an emphasis on ferroptosis. Wild-type and cardiac metallothionein transgenic mice received GSH synthase inhibitor buthionine sulfoximine (BSO; 30 mmol/L in drinking water) for 14 days before assessment of myocardial morphology and function. BSO evoked cardiac remodeling and contractile anomalies, including cardiac hypertrophy, interstitial fibrosis, enlarged left ventricular chambers, deranged ejection fraction, fraction shortening, cardiomyocyte contractile capacity, intracellular Ca2+ handling, sarcoplasmic reticulum Ca2+ reuptake, loss of mitochondrial integrity (mitochondrial swelling, loss of aconitase activity), mitochondrial energy deficit, carbonyl damage, lipid peroxidation, ferroptosis, and apoptosis. Metallothionein itself did not affect myocardial morphology and function, although it mitigated BSO-provoked myocardial anomalies, loss of mitochondrial integrity and energy, and ferroptosis. Immunoblotting revealed down-regulated sarco(endo)plasmic reticulum Ca2+-ATPase 2a, glutathione peroxidase 4, ferroptosis-suppressing CDGSH iron-sulfur domain 1 (CISD1), and mitochondrial regulating glycogen synthase kinase-3ß phosphorylation with elevated p53, myosin heavy chain-ß isozyme, IκB phosphorylation, and solute carrier family 7 member 11 (SLC7A11) as well as unchanged SLC39A1, SLC1A5, and ferroptosis-suppressing protein 1 following BSO challenge, all of which, except glutamine transporter SLC7A11 and p53, were abrogated by metallothionein. Inhibition of CISD1 using pioglitazone nullified GSH-offered benefit against BSO-induced cardiomyocyte ferroptosis and contractile and intracellular Ca2+ derangement. Taken together, these findings support a regulatory modality for CISD1 in the impedance of ferroptosis in metallothionein-offered protection against GSH depletion-evoked cardiac aberration.

Secondhand smoking exposure and quality of life among pregnant and postnatal women: a network approach.

OBJECTIVE: This study examined the prevalence of exposure to secondhand smoke, its correlates and its association with quality of life (QOL) among pregnant and postnatal Chinese women. DESIGN: This was a multicentre, cross-sectional study. SETTING: Participants were consecutively recruited from eight tertiary hospitals located in eight municipalities or provinces in China. PARTICIPANTS: A total of 1140 women were invited to join this study and 992 (87.02%) completed all measures. PRIMARY AND SECONDARY OUTCOME: Measures women's secondhand smoking behaviour (frequency and location of exposure to secondhand smoking), and their QOL measured by the WHO Quality of Life Questionnaire. RESULTS: A total of 211 women (21.3%, 95% CI 18.7% to 23.8%) had been exposed to secondhand smoking. Exposure to secondhand smoking was most common in public areas (56.4%), and residential homes (20.5%), while workplaces had the lowest rate of exposure (13.7%). Women with physical comorbidities were more likely to report secondhand smoking exposure, while older women, women living in urban areas, those with college or higher education level, and women in their second trimester were less likely to report exposure to secondhand smoking. Network analysis revealed that there were six significant links between secondhand smoke and QOL items. The strongest negative edge was the connection between secondhand smoke and QOL9 ('physical environment health', edge weight=-0.060), while the strongest positive edge was the connection between secondhand smoke and QOL3 ('pain and discomfort', edge weight=0.037). CONCLUSION: The prevalence of exposure to secondhand smoking is becoming lower among pregnant and postnatal women in China compared with findings reported in previous studies. Legal legislation should be maintained and promptly enforced to establish smoke-free environments in both public and private urban/rural areas for protection of pregnant and postnatal women, especially those who are physically vulnerable and less educated.

Prevalence, correlates, and network analysis of Internet addiction symptoms among Chinese pregnant and postpartum women.

OBJECTIVE: Excessive Internet use is a common health problem globally. This study aimed to assess the prevalence, correlates, and network structure of Internet addiction symptoms (Internet addiction hereafter) among Chinese pregnant and postpartum women. METHODS: This was a multicenter cross-sectional study using Internet Addiction Test (IAT) and the World Health Organization Quality of Life Questionnaire (WHOQOL-BREF) to evaluate Internet addiction and quality of life (QOL), respectively. Univariate analyses, multivariate logistic regression analyses, and network analyses were performed. RESULTS: Of a total of 1,060 women who completed the study, 320 (30.19%, 95% CI=27.42%-32.96%) women reported Internet addiction during or after pregnancy. Women with previous adverse pregnancy experiences (OR=1.831, P=0.001) and physical comorbidities (OR=1.724, P=0.004) had a higher likelihood of developing Internet addiction. Internet addiction was significantly associated with poor QOL in all domains. Network analyses revealed that IAT item 16 (request an extension for longer time spent online) was the most central symptom in the analyses, and also one of the strongest bridging symptoms linking the Internet addiction and QOL communities. LIMITATIONS: This was a cross-sectional study, all study findings were based on self-reported data, and possible recall bias and selection bias may exist. CONCLUSION: Internet addiction is common among Chinese pregnant and postpartum women, and is significantly associated with lower QOL. Effective strategies, especially focusing on central symptoms, are needed to reduce the impact of Internet addiction and improve QOL in pregnant and postpartum women.

The Prevalence of Depression and Its Association With Quality of Life Among Pregnant and Postnatal Women in China: A Multicenter Study.

Background: This study examined the prevalence of depressive symptoms (depression hereafter) and its association with quality of life (QOL) among pregnant and postnatal women in China. Methods: In this multi-center, cross-sectional study, 1,060 pregnant and postnatal women from eight hospitals were assessed. Depression and QOL were measured using the Edinburgh Postnatal Depression Scale and the World Health Organization Quality of Life Questionnaire - brief version, respectively. Results: The prevalence of depression was 7.45% (95% CI: 5.87-9.04%) in the sample. Women with depression had lower QOL in physical, psychological, social and environmental domains compared to those without. Women with physical comorbidities were more likely to suffer from depression (OR = 2.391, 95% CI = 1.384-4.130, P = 0.002). Conclusion: Due to its negative association with QOL, increased attention should be paid to depression in pregnant and postnatal women. Regular screening assessment and preventive measures should be adopted to reduce risk of depression in this population.

A review and comparison of common maternal positions during the second-stage of labor.

The second-stage of labor is the most stressful part of childbirth process and the proper maternal position during this period is paramount for women's safe vaginal birth. Midwives play a pivotal role in managing maternal positions during the second-stage of labor. However, there is limited evidence to support an ideal maternal position during the second-stage of labor. Further, the difference between different maternal positions might not be apparent. This paper aims to review and compare the benefits and risks of common maternal positions during the second-stage of labor, thereby to provide midwives evidence-based practical guidelines.

Involvement of the MiR-181b-5p/HMGB1 Pathway in Ang II-induced Phenotypic Transformation of Smooth Muscle Cells in Hypertension.

Phenotypic transformation of vascular smooth muscle cells (VSMCs) contributes to vascular remodeling in hypertension. High mobility group box-1 (HMGB1) has been reported to be involved in several pathogenic processes including VSMC proliferation and migration. The present study was designed to determine the role of HMGB1 in VSMC phenotypic transformation in hypertension. First, we demonstrated that HMGB1 was elevated in a model of Ang II-induced VSMC phenotypic transformation, which showed down-regulation of contractile proteins and up-regulation of synthetic proteins. Knockdown of HMGB1 and losartan could block the phenotypic transformation. Next, we identified three potential miRNAs for upstream regulation of HMGB1 by bioinformatic analysis; only miR-181b-5p was significantly down-regulated in Ang II-treated cells. Co-treating the cells with miR-181b-5p mimics suppressed HMGB1 expression as well as the phenotypic transformation, migration, and proliferation. Furthermore, the luciferase reporter gene assay confirmed the direct interaction between miR-181b-5p and HMGB1. Finally, to extend these cell-based studies to clinical patients, we demonstrated that plasma miR-181b-5p levels were decreased, while Ang II and HMGB1 levels, as well as the intima-media thickness (IMT) were increased in hypertensive patients; these effects were reversed following the administration of angiotensin receptor blockers. Based on these observations, we conclude that the down-regulation of miR-181b-5p leads to the elevation of HMGB1 levels in hypertensive patients, which accounts, at least partially, for VSMCs phenotypic transformation and vascular remodeling. Our findings also highlight that the plasma levels of miR-181b-5p and HMGB1 may serve as novel biomarkers for vascular remodeling in the hypertensive patients.

The role of 5-hydroxymethylcytosine in melanoma.

Malignant melanoma is a highly aggressive neoplasia of melanocytic origin. In part because of the lack of effective treatment methods, the incidence and mortality rates of this disease continue to increase. Rapidly accumulating evidence suggests that dysregulation of epigenetic mechanisms, including DNA methylation/demethylation, chromatin modification, and remodeling, and diverse activities of noncoding RNAs, play a central role in the pathogenesis of melanoma. The epigenetic mark 5-hydroxymethylcytosine (5-hmC) has attracted interest since 2009, when it was shown that ten-eleven translocation proteins can enzymatically convert 5-methylcytosine into 5-hmC, a key intermediate of DNA demethylation. Factors that regulate DNA hydroxymethylation are frequently altered in cancer, leading to deregulation of 5-hmC levels. In this review, we will discuss the relationship between melanoma and DNA hydroxymethylation, the regulation of DNA hydroxymethylation, and defects in this pathway in melanoma.

Pleurotus nebrodensis polysaccharide (PN-S) enhances the immunity of immunosuppressed mice.

In the present study, the effects of Pleurotus nebrodensis polysaccharide (PN-S) on the immune functions of immunosuppressed mice were determined. The immunosuppressed mouse model was established by treating the mice with cyclophosphamide (40 mg/kg/2d, CY) through intraperitoneal injection. The results showed that PN-S administration significantly reversed the CY-induced weight loss, increased the thymic and splenic indices, and promoted proliferation of T lymphocyte, B lymphocyte, and macrophages. PN-S also enhanced the activity of natural killer cells and increased the immunoglobulin M (IgM) and immunoglobulin G (IgG) levels in the serum. In addition, PN-S treatment significantly increased the phagocytic activity of mouse peritoneal macrophages. PN-S also increased the levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), interferon-γ (INF-γ), and nitric oxide (NOS) in splenocytes. qRT-PCR results also indicated that PN-S increased the mRNA expression of IL-6, TNF-α, INF-γ, and nitric oxide synthase (iNOS) in the splenocytes. These results suggest that PN-S treatment enhances the immune function of immunosuppressed mice. This study may provide a basis for the application of this fungus in adjacent immunopotentiating therapy against cancer and in the treatment of chemotherapy-induced immunosuppression.

[The relevance between the effect on dysmenorrhea and the time of surgery of artery embolization in the treatment of adenomyosis].

OBJECTIVE: To analyze the relevance between the effect on dysmenorrhea of uterine artery embolization (UAE) in treatment of adenomyosis (AM) in different periods of the menstrual cycle and the time of the operation. METHODS: Totally 225 cases with preoperative dysmenorrhea voluntarily chose UAE in treatment of AM. They were divided into two groups according to the different times of menstrual cycle (proliferative phase or secretory phase). We analyzed the relevance between the effect of dysmenorrhea of patients in the two groups with the time of surgery after 1, 2, 3 and 4 years. RESULTS: (1) The numbers of the cases completely followed up were 142, 128, 119 and 101 each year in the following four years. (2) The effective rate on dysmenorrhea in the two groups of AM patients was 81% (43/53) and 76% (68/89) after 1 year (P > 0.05). (3) The effective rate was 75% (36/48) and 70% (56/80) after 2 years (P > 0.05). (4) The effective rate was 70% (32/46) and 63% (46/73) after 3 years (P > 0.05). (5) The effective rate was 63% (24/38) and 63% (40/63) after 4 years (P > 0.05). CONCLUSION: UAE has a good efficacy in treatment of AM, but the relevance is not significant between the time of surgery and the effectiveness on dysmenorrhea.

Differential expression of endogenous ferritin genes and iron homeostasis alteration in transgenic tobacco overexpressing soybean ferritin gene.

For studying the effects of endogenous ferritin gene expressions (NtFer1, GenBank accession number AY083924; and NtFer2, GenBank accession number AY141105) on the iron homeostasis in transgenic tobacco (Nicotiana tabacum L.) plants expressing soybean (Glycine max Merr) ferritin gene (SoyFer1, GenBank accession number M64337), the transgenic tobacco has been produced by placing soybean ferritin cDNA cassette under the control of the CaMV 35S promoter. The exogenous gene expression was examined by both Northern- and Western-blot analyses. Comparison of endogenous ferritin gene expressions between nontransformant and transgenic tobacco plants showed that the expression of NtFer1 was increased in the leaves of transgenic tobacco plants, whereas the NtFer2 expression was unchanged. The iron concentration in the leaves of transgenic tobacco plants was about 1.5-folds higher than that in nontransformant. Enhanced growth of transgenic tobacco was observed at the early development stages, resulting in plant height and fresh weights significantly greater than those in the nontransformant. These results demonstrated that exogenous ferritin expression induced increased expression of at least one of the endogenous ferritin genes in transgenic tobacco plants by enhancing the ferric chelate reductase activity and iron transport ability of the root, and improved the rate of photosynthesis.