Protective effect of quercetin on lipopolysaccharide­induced miscarriage based on animal experiments and network pharmacology.

Spontaneous abortion (SA) occurs in woman of child­bearing age, jeopardizing their physical and mental health. Quercetin is a natural flavonoid, which exhibits a variety of pharmacological activities. However, the role and mechanisms of quercetin in SA still need to be further explored. Animal experiments were performed to examine the effect of quercetin in treating SA. Institute of Cancer Research mice were injected with lipopolysaccharide into the tail vein on the 7th day of gestation to establish a SA model. Gavage was performed during days 3­8 of gestation with high­, medium­ and low­dose of quercetin. Then the effect of quercetin on embryos was evaluated. Animal experiment showed that quercetin could remarkably reduce the embryo loss rate and increase the mean weight of surviving embryos to some degree. Furthermore, network pharmacology was employed to explore the underlying mechanisms of quercetin in the treatment of SA. Several databases were used to collect the targets of SA and quercetin. Protein­protein interaction network, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis were performed to elucidate the interactions between SA and quercetin. The relative mRNA expressions of several targets in uterine were detected by quantitative reverse transcriptase polymerase chain reaction (RT­qPCR). Network pharmacology indicated that the effects of quercetin in treating SA were mainly related to hormone response and the modulation of defense response and inflammatory response, involving signaling pathways such as PI3K­Akt, VEGF, MAPK and core targets such as AKT1, albumin, caspase­3. RT­qPCR showed that quercetin could up­regulate AKT1, MAPK1, PGR, SGK1 and down­regulate ESR1, MAPK3. The results showed that quercetin may modulate multiple signaling pathways by targeting core targets to prevent and treat SA.

The role of serum-glucocorticoid regulated kinase 1 in reproductive viability: implications from prenatal programming and senescence.

OBJECTIVE: Organisms and cellular viability are of paramount importance to living creatures. Disruption of the balance between cell survival and apoptosis results in compromised viability and even carcinogenesis. One molecule involved in keeping this homeostasis is serum-glucocorticoid regulated kinase (SGK) 1. Emerging evidence points to a significant role of SGK1 in cell growth and survival, cell metabolism, reproduction, and life span, particularly in prenatal programming and reproductive senescence by the same token. Whether the hormone inducible SGK1 kinase is a major driver in the pathophysiological processes of prenatal programming and reproductive senescence? METHOD: The PubMed/Medline, Web of Science, Embase/Ovid, and Elsevier Science Direct literature databases were searched for articles in English focusing on SGK1 published up to July 2023 RESULT: Emerging evidence is accumulating pointing to a pathophysiological role of the ubiquitously expressed SGK1 in the cellular and organismal viability. Under the regulation of specific hormones, extracellular stimuli, and various signals, SGK1 is involved in several biological processes relevant to viability, including cell proliferation and survival, cell migration and differentiation. In line, SGK1 contributes to the development of germ cells, embryos, and fetuses, whereas SGK1 inhibition leads to abnormal gametogenesis, embryo loss, and truncated reproductive lifespan. CONCLUTION: SGK1 integrates a broad spectrum of effects to maintain the homeostasis of cell survival and apoptosis, conferring viability to multiple cell types as well as both simple and complex organisms, and thus ensuring appropriate prenatal development and reproductive lifespan.

Effects of quercetin on immune regulation at the maternal-fetal interface. / æ§²çš®ç´ å¯¹æ¯èƒŽç•Œé¢å ç–«è°ƒèŠ‚çš„å½±å“.

The imbalance of immune homeostasis at the maternal-fetal interface is closely related to adverse pregnancy outcomes, so it has become one of the hot research topics in the reproductive field. Quercetin is rich in common TCM kidney-tonifying herbs such as dodder and lorathlorace, and has shown pregnancy protection function. As a common flavonoid, quercetin has powerful anti-inflammatory, antioxidant, estrogen-like effects; and it can regulate the functions of maternal-fetal interface immune cells (such as decidual natural killer cells, decidual macrophages, T cells, dendritic cells and myeloid-derived suppressor cells), exovillous trophoblast cells, decidual stromal cells, and the activities of their cytokines. Quercetin maintains the dynamic balance of maternal and fetal immunity by attenuating cytotoxicity, reducing excessive apoptosis of the tissue cells and inhibiting excessive inflammatory reactions. In this article, the role and molecular mechanism of quercetin in the immunomodulatory process of the maternal and fetal interface are reviewed to provide reference for the treatment of recurrent spontaneous abortion and other adverse pregnancy outcomes.

Chinese traditional herbs enhanced the clinical efficacy of low-molecular-weight heparin in the treatment of recurrent spontaneous abortion complicated with thrombophilia.

Thrombophilia is an important cause of recurrent spontaneous abortion (RSA). The treatment of thrombophilia is beneficial to the prevention of RSA. Therefore, we explored the clinical effect of Chinese traditional herbs with the effects of invigorating the blood, tonifying the kidney and calming the fetus in the treatment of RSA complicated with thrombophilia. We retrospectively analyzed the clinical outcomes of 190 RSA patients combined with thrombophilia using different treatment methods. The traditional Chinese medicine group was treated with kidney-invigorating, blood-activating and fetus-soothing herbs and the western medicine group was treated with low molecular weight heparin (LMWH), and the traditional Chinese medicine combined with western medicine group was treated with LMWH plus Chinese traditional herbs with the effects of kidney tonifying, blood activating and fetus stabilizing. After treatments, platelet aggregation rate, plasma D-dimer and uterine artery blood flow resistance were significantly reduced in the LMWH plus herbs compared to the simple herbs and LMWH group (P < 0.0167). The LMWH plus herbs group significantly accelerated the growth of fetal bud compared with other groups (P < 0.0167). Moreover, the LMWH plus herbs group improved traditional Chinese medicine syndrome scores (P < 0.0167), showing a better clinical efficacy. Adverse reactions occurred in five patients in the LMWH group but not in the simple herbs and LMWH plus herbs group during the treatment period. Therefore, our study shows that for the treatment of RSA complicated with thrombophilia, Chinese traditional herbs plus LMWH can improve the blood supply of the uterus during pregnancy and contribute to a favorable environment for the growth of the fetus. Chinese traditional herbs exert a good curative effect with few adverse reactions.

Association between depression or anxiety symptoms and immune-inflammatory characteristics in in-patients with tuberculosis: A cross-sectional study.

Background: Depression and anxiety are major psychological issues among patients with tuberculosis (TB) owing to chronic and complex treatments, have been reported to be closely correlated with immune and inflammation. However, the association of peripheral immune-inflammatory characteristics with depression/anxiety symptoms in in-patients with TB has rarely been reported. Methods: A cross-sectional study of 338 in-patients with TB from 3 hospitals in China were enrolled to investigate their depression and anxiety status by using the nine-item Patient Health Questionnaire (PHQ-9) and seven-item Generalized Anxiety Disorder Scale (GAD-7). Participants were divided into groups based on their PHQ-9 and GAD-7 scores, and differences in demography and immune-inflammatory characteristics were studied. Logistic analysis was performed to explore factors related to depression and anxiety symptoms. Results: Depression and anxiety prevalence among patients with TB was 47.9 and 42.6%, respectively. Furthermore, 38.5% of patients reported a comorbidity of depression and anxiety symptoms. The counts of CD3, CD4, CD8, and lymphocytes decreased, whereas those of neutrophils, platelets, and peripheral blood cells and their derived indices increased among TB patients with depression or anxiety in comparison with those without symptoms (p < 0.05). In addition, increasing age, lower income (monthly income ≤ 3,000 yuan), divorced or widowed, drug resistance, and higher systemic immune inflammation index (SII) were significantly associated with depression or anxiety symptoms (p < 0.05). Conclusion: Approximately half of the patients with TB suffered from depression or/and anxiety symptoms. Patients with depression or anxiety present worse cell immune status and stronger inflammatory responses compared to those without symptoms. We emphasized the importance of paying attention to the dysfunction of immune-inflammation process of TB patients with depression or anxiety symptoms. Especially, SII has a potential application value in guiding the evaluation of TB-related depression or anxiety owing to its easily accessibility and being economical.

Sleep quality and its associated factors among patients with tuberculosis: A cross-sectional study.

Background: Tuberculosis (TB) patients commonly suffer from sleep issues owing to various adverse drug reactions (ADRs), disease symptoms, and the contagious nature of their disease. These sleep issues negatively affect the treatment outcome and quality of life. However, the prevalence of sleep disturbance and its associated factors among TB patients have rarely been reported. Methods: A total of 497 inpatients with TB from three hospitals in China were enrolled in this cross-sectional study to investigate their sleep quality using the Pittsburgh sleep quality index (PSQI). Clinical data, including demographic information, TB-related stigma, perceived stress, and nutrition- and immunity-related indicators, were also collected to explore the factors associated with sleep disturbance among the recruited patients. Results: Approximately 70% of the recruited patients reported a sleep disturbance to varying degrees, presenting poorer global and subjective sleep qualities, longer sleep latency, shorter sleep duration, lower sleep efficiency, more frequent sleep disturbances, greater use of sleeping medication, and more severe daytime dysfunction. Furthermore, the body mass index (BMI), hemoglobin levels, albumin levels, and T lymphocyte count of the patients in the poor sleep quality group were significantly lower than those in the good sleep quality group (p < 0.05). Increasing age, higher income, drug resistance, higher stigma or stress perception, lower albumin levels, and lower CD4 levels were significantly associated with sleep disturbance among TB patients (p < 0.05). Conclusion: Three-quarters of the participants were found to suffer from a probable sleep disturbance. And sleep problems are linked to biological traits that interact with psychological, cultural, and social factors in complex ways. It is therefore important to pay attention to the sleep quality of TB patients, especially those with the identified risk factors. Besides, taking care of these risk factors may prove to be an effective sleep management strategy.