Lower Fiber Consumption in Women with Polycystic Ovary Syndrome: A Meta-Analysis of Observational Studies.

Polycystic ovary syndrome is a common endocrine disorder associated with metabolic abnormalities and gut microbiota dysbiosis. The deficiency of dietary fiber, a crucial nutrient in the daily diet, is also associated with a wide range of metabolic and reproductive abnormalities, as well as an altered gut microbial ecosystem. This study is a meta-analysis to summarize the available evidence on the dietary fiber intake level in PCOS patients. Databases of PubMed, Embase, Cochrane Library, Web of Science, and ClinicalTrials.gov were searched for observational studies, and 13 studies were finally included. The pooled standardized mean difference (SMD) with the 95% confidence interval (CI) of daily dietary fiber intake and total energy intake were calculated using the random-effects model. The pooled result (12 studies) on absolute dietary fiber intake showed that while there was no significant difference in the total energy intake [−0.17 (−0.44, 0.09), p = 0.208], the dietary fiber intake was significantly lower in PCOS women than those of controls [−0.32 (−0.50, −0.14), p < 0.001]. However, significant heterogeneity was detected across the studies (I2 = 65.6%, p = 0.001). Meta-regression suggested that geographic region and dietary assessment method may confer borderline significance of influence on the heterogeneity. The pooled result (two studies) on dietary fiber intake which adjusted for total energy intake, however, showed no significant difference [−2.11 (−4.77, 0.56), p = 0.122]. In subgroup analyses based on absolute dietary fiber intake, a lower dietary fiber intake in PCOS was observed in studies conducted in Asia, adopted food diary or records or food recall as the dietary assessment method, had a case−control study design, or used Rotterdam criteria for PCOS diagnosis. The difference in SMD was still significant in the adult subgroup or in studies matched or unmatched for age.

Effect of dehydroepiandrosterone on atherosclerosis in postmenopausal women.

In China, cardiovascular disease (CVD) has surpassed malignant tumours to become the disease with the highest mortality rate, and atherosclerosis (AS) is an important pathological cause of CVD. Dehydroepiandrosterone (DHEA) is the most abundant steroid hormone in circulating human blood and is a precursor of estrogen and androgen. DHEA is converted into a series of sex hormones in local peripheral tissues where its acts physiologically. DHEA also acts therapeutically, thereby avoiding the adverse systemic reactions to sex hormones. DHEA inhibits AS, thus inhibiting the development of CVD, and it improves the prognosis for CVD. The incidence of CVD in postmenopausal women is substantially higher than that in premenopausal women, and that incidence is believed to be related to a decrease in ovarian function. The current review analyzes the mechanisms of postmenopausal women's susceptibility to AS. They tend to have dyslipidemia, and their vascular smooth muscle cells (VSMCs) proliferate and migrate more. In addition, oxidative stress and the inflammatory response of endothelial cells (ECs) are more serious in postmenopausal women. This review also discusses how DHEA combats AS by countering these mechanisms, which include regulating the blood lipid status, protecting ECs (including coping with oxidative stress and inflammatory reactions of the vascular endothelium, inhibiting apoptosis of ECs, and inducing NO production) and inhibiting the proliferation and migration of VSMCs. As a result, DHEA has great value in preventing AS and inhibiting its progression in postmenopausal women.

Effect and mechanism of berberine against polycystic ovary syndrome.

For women of reproductive age, polycystic ovary syndrome (PCOS) is not a rare heterogeneous endocrine disorder and metabolic dysfunction. Menstrual problems, hyperandrogenism, polycystic ovary (PCO) and infertility often affect these women, and they are also prone to metabolic syndrome (MS) and insulin resistance (IR). As an isoquinoline alkaloid, Berberine (BBR) is the main effective component of Coptis. BBR, as a multi-target, multi-path plant extract, can interfere with the development of PCOS and relate to pathological process from many aspects, with less adverse reactions. It is mentioned in this review that BBR can alleviate IR, reduce the level of serum androgen, regulate lipid metabolism and moderate chronic inflammation. BBR is often used in combination with metformin, compound cyproterone (CPA) and other drugs, in order to achieve better therapeutic effect on PCOS.

Alterations in the intestinal microbiome associated with PCOS affect the clinical phenotype.

Polycystic ovarian syndrome (PCOS), characterized by chronic anovulation and hyperandrogenaemia, is a complex endocrine and metabolic disorder commonly seen in women of reproductive age. Multiple factors, including the intestinal microbiome, affect the pathogenesis and development of PCOS. However, the specific mechanisms by which gut microbes play a role in PCOS remain elusive. This review summarizes recent research about the transformational changes in gut microbes revealed in PCOS patients and the possible mechanisms and pathways by which the intestinal microbiome exerts influence on PCOS progression and phenotypes. In addition to the intestinal microbiome, evidence from animal studies suggests changes in the vaginal microbiome under PCOS conditions. The alteration of microbiome could affect oestrus cycle and PCOS phenotypes. Microbiome is closely associated with medicine and therapeutic approaches. Microbiome influences drug and therapy response and itself is a new source of therapy. Accurate modulation of the intestinal and vaginal microbiome is a potential therapy for PCOS patients. Future studies are required to elucidate the specific role of each particular genera of microbiota and the mechanism by which microbiome impacts the pathogenesis, progression and phenotypes of PCOS.

Half depletion of Foxp3+ regulatory T cells by diphtheria toxin for long-term study in vivo.

Depletion of regulatory T cells (Tregs) is an appropriate approach to study the function of Tregs in vivo, and most previous studies have focused on complete depletion. The purpose of the current study was to determine an appropriate dose and timing for half depletion of Tregs in vivo. DETREG (DEpletion of REGulatory T cells) mice were produced and injected with different doses of diphtheria toxin (DT) for 7 days and 14 days. The mice were then sacrificed to collect the spleen and mesenteric lymph nodes (MLN) for analysis using flow cytometry. Foxp3+eGFP+ cells were significantly reduced by DT injection. A dose of 5 ug/kg DT led to half depletion and no deaths. A DT dose of 25, 50, or 100 ug/kg led to a progressively higher depletion rate but also a higher mortality rate. In conclusion, a low dose of DT is effective for half depletion of Tregs and long-term study. Half depletion of Tregs may become a new method for the future study of Tregs in vivo.

A basic understanding of mucopolysaccharidosis: Incidence, clinical features, diagnosis, and management.

Mucopolysaccharidoses (MPS) are a group of rare lysosomal storage diseases (LSD) with multi-organic and severe symptoms. MPS occur worldwide in various forms though have relative a low incidence. The prevalent type of MPS varies among different continents, indicating that it may be associated with region and ethnic background. Undegraded glycosaminoglycans (GAGs) induced by deficiency of enzymes are the primary cause of MPS. Clinical features differ depending on the specific enzyme deficiency including coarse facial features, cognitive retardation, hepatosplenomegaly, hernias, kyphoscoliosis, corneal clouding, etc. Symptoms of different types are usually similar especially MPS I and II, but may have distinguishable features such as severe neurological problems in MPS III and hydrops fetails in MPS VII. These clinical features contribute to diagnosis, but early and precisely diagnosis in the asymptomatic stage is imperative for better outcomes. Novel approaches including urinary and blood GAG test, enzyme assay and gene test help to diagnose MPS and to determine its subtype. Hematopoietic stem cell transplantation (HSCT) and enzyme replacement therapy (ERT) are conventional treatment for MPS, but are not effective at treating all MPS. Newer threatments, such as advanced ERT, gene therapy and substrate reduction therapy (SRT), improve therpeutic efficacy. In this review, we update information on the clinical manifestations, diagnosis, and treatment of the different forms of this disease in the hopes of stimulating further interest in MPS.

The novel role of Hippo-YAP/TAZ in immunity at the mammalian maternal-fetal interface: Opportunities, challenges.

The Hippo-Yes-associated protein (YAP)/transcriptional co-activator with PDZ-binding motif (TAZ), originally identified as a regulator of tissue generation and tumorigenesis, has been proven to have a pivotal position in immunity. Its multi-faceted roles in regulating immunity cover both intrinsic mechanism of immune cells and the crosstalk with non-immune cells. Survival of the allogeneic embryo in the maternal uterine environment depends on immune tolerance, supported by the highly orchestrated cooperation between decidual immune cells, decidual stromal cells and trophoblasts at the maternal-fetal interface. The abnormal maternal-fetal dialogue is believed to be associated with adverse pregnancy outcomes such as spontaneous pregnancy loss. Recent breakthroughs shed light on the how the Hippo-YAP/TAZ manipulate the decidualization and trophoblast invasion, while further research is needed to integrate and reconcile existing findings of the Hippo-YAP/TAZ in immunity and to extend them at the context of pregnancy. In this review, we summarized the Hippo-YAP/TAZ pathways, detailed the effects of YAP/TAZ on immune cells, and discussed the role of YAP/TAZ at the maternal-fetal interface and the potential of YAP/TAZ on immunity regulation at the context of pregnancy. Given the remarkable effect of therapeutic intervention of YAP/TAZ in cancer and autoimmune diseases, it is worthy to explore the response to YAP/TAZ inhibition in the maternal-fetal immunity. This may provide a new valuable target for therapy of pregnancy loss, or potentially other pregnancy complications.

Alterations of Several Serum Parameters Are Associated with Preeclampsia and May Be Potential Markers for the Assessment of PE Severity.

The precise pathophysiological mechanisms of preeclampsia (PE) and preventative strategies remain unknown. Laboratory markers which can help in identifying PE patients from pregnant women and assessing the severity of PE during pregnancy are worthy to be explored. In this study, a retrospective case-control study was designed to assess whether the serum levels of albumin (ALB), total protein (TP), prealbumin (PA), alkaline phosphatase (ALP), lactic dehydrogenase (LDH), D-dimer, fibrinogen (Fbg), platelet (PLT) count, mean platelet volume (MPV), and platelet distribution width (PDW) can help in assessing PE and evaluate its severity. 256 pregnant women were enrolled and classified into 3 groups: mild preeclampsia (mPE, n = 85), severe preeclampsia (sPE, n = 78), and healthy normotensive controls (control, n = 93). Our result showed that the serum levels of ALP, LDH, and D-dimer were significantly higher in mild or severe PE patients compared with the healthy controls (66 (52.5-76.5) vs. 168 (141.5-201.25) vs. 182.5 (120-191.5), 152 (139.75-166.25) vs. 183.5 (163.25-307) vs. 282 (215.25-306), 1.05 (0.65-1.57) vs. 3.05 (2.25-4.08) vs. 5.65 (2.29-7.71)), while ALB, TP, and PA are lower (38 (37-42) vs. 31.5 (25.5-34.5) vs. 28.5 (24-33), 65 (63-68.25) vs. 56.5 (52-61) vs. 51.5 (49-58), 219.14 ± 68.25 vs. 167.88 ± 52.21 vs. 143.22 ± 50.46). On the other hand, compared with the mPE group, the sPE group showed significantly lower PLT count but higher level of LDH, D-dimer, and Fbg. No significant differences in MPV or PDW were found between any of the two groups. In conclusion, the above markers except for the MPV and PDW may be correlated with PE severity in this patient cohort, indicating possible values of these potential biomarkers in auxiliary diagnosis and severity assessment of PE.

Chinese herbal medicine for acute upper respiratory tract infections and reproductive safety: A systematic review.

Acute upper respiratory tract infections (AURTIs) are common and self-limited in people with normal immunity but sometimes lead to poor clinical outcomes under specific conditions such as pregnancy if not treated appropriately. Chinese herbal medicines (CHM), which are widely used to treat AURTIs, have proven to be effective in preclinical and clinical studies. This review focuses on the bioactivities of typical CHM and the adverse reactions they cause, and especially issues with reproductive safety when treating AURTIs. The main mechanisms for clinical efficacy may include anti-viral, anti-bacterial, anti-inflammatory, antipyretic, and immunomodulatory action as indicated by preclinical evidence. Most clinical trials indicate that CHM shortens the natural course of AURTIs and that it relieves related symptoms such as a fever, headaches, coughing, myalgia, a cold, sore throat, and a nasal obstruction. However, some CHM have a range of adverse effects and potentially affect reproduction from endocrinal secretion to embryo development while others do not. Therefore, clinical adverse reactions and preclinical studies on the toxicity of CHM are discussed. More reliable evidence is required to conclude that CHM are efficacious and safe for pregnant women with AURTIs. This review should help to promote advances in the research on and development of CHM as alternative treatments for AURTIs and offer insight into strategies to manage the safety of CHM during clinical use.

Sperm DNA fragmentation valued by SCSA and its correlation with conventional sperm parameters in male partner of recurrent spontaneous abortion couple.

The objective of this study is to evaluate the predictive value of sperm DNA fragmentation Index (DFI) in unexplained recurrent spontaneous abortion (RSA) and to investigate its correlation with conventional sperm parameters. Besides, we aimed to reveal the necessity of establishing a DFI clinical threshold of each laboratory for the prognostic diagnosis of RSA and establish our own DFI threshold. Semen samples were collected from male partners of RSA patients (n = 139) and healthy recent fathers (control, n = 200). DFI was tested using SCSA and conventional semen analysis was performed using an automatic semen analyzer. The DFI value and distribution were compared between the two groups using corresponding statistical software. The diagnostic threshold value was established by ROC curve. The correlation between DFI and the conventional semen parameters of the 139 cases was further analyzed using Student's t test and Mann-Whitney U test. Our result showed that DFI was significantly higher in RSA patients compared with normal donor controls. We established our own DFI threshold at 13.59%. There was only a weak partial correlation between DFI values and conventional sperm analysis parameters. Our present study suggested that DFI might be used as a valuable predictor for RSA independent of conventional sperm parameters. Additionally, we recommend that each laboratory should establish its own clinical DFI threshold for more precise prediction of RSA and we recommend that sperm DNA fragmentation test should be included in complete sperm quality assessment in addition to conventional semen analysis for RSA male partners.

New thoughts in exploring the pathogenesis, diagnosis, and treatment of threatened abortion.

Threatened abortion is a common complication of pregnancy. Since the underlying mechanisms behind this condition are complicated, predicting and treating threatened abortion is a challenge for clinicians. Interestingly, a recent article in Bioscience Trends (Biosci Trends 2019; DOI: 10.5582/bst.2019.01111) revealed a higher, not lower, level of ꞵ-human chorionic gonadotropin (hCG) and estrogen during the first 6 weeks of pregnancy, suggesting a novel association between ꞵ-hCG, estrogen, and threatened abortion. Unfortunately, this study was limited by its small sample size, unconvincing trial design, and inadequate exploration of the underlying mechanisms. This low-quality evidence indicates that a higher level of ꞵ- hCG and estrogen is associated with threatened abortion. However, that work provided some new insights for further studies of threatened abortion.

Hydroxychloroquine reverses the drug resistance of leukemic K562/ADM cells by inhibiting autophagy.

Autophagy is an essential metabolic pathway mediated by lysosomal degradation, which is involved in scavenging and recycling senescent or damaged organelles and biological macromolecules in eukaryotic cells. The present study explored the association between the autophagic activity and chemotherapy resistance of leukaemia cells, and the possibility of using autophagy inhibitors to combat leukemic drug resistance. It was found that the levels of basic autophagy in multidrug­resistant leukaemia cells (K562/ADM) were significantly higher compared with sensitive cells (K562), and that Adriamycin (ADM) was capable of inducing autophagic activity in K562 and K562/ADM cells. K562 and K562/ADM cells were treated with a series of hydroxychloroquine (HCQ) concentrations to inhibit cellular autophagy and detect cell sensitivity to ADM. The results demonstrated that the sensitivity of K562 cells to ADM was mildly enhanced by HCQ, and that the sensitivity of K562/ADM cells to ADM was markedly strengthened by HCQ. In addition, more typical morphological changes associated with apoptosis emerged, and the ratio of Bax/Bcl­2 and activity of caspase­3 were markedly increased in K562/ADM cells treated with HCQ. Notably, the expression of mdr1 mRNA and P­glycoprotein (P­gp) in drug­resistant K562/ADM cells was upregulated along with increasing autophagic activity induced by ADM. Furthermore, HCQ significantly reduced the increase in P­gp expression by inhibiting autophagic activity. Collectively, these findings indicated that the inhibition of autophagy significantly promoted the sensitivity of K562/ADM cells to ADM by facilitating apoptosis. Furthermore, inhibition of autophagy attenuated the expression of P­gp; therefore, P­gp may be involved in autophagic regulation in drug­resistant cells.