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Background: Significant challenges are associated with the pharmacological management of dyslipidemia, an important risk factor for cardiovascular disease. Limited reliable evidence exists regarding the efficacy of red yeast rice (RYR)-containing commercial Chinese polyherbal preparation (CCPP), despite their widespread use in China. Purpose: We aimed to investigate the efficacy of RYR-containing CCPPs combined with statins in treating dyslipidemia. Methods: Eight databases were searched for relevant randomized controlled trials (RCTs) from database inception date to November 2023. Outcome measures, including low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), total cholesterol (TC), triglyceride (TG), clinical efficacy, and adverse reactions, were assessed. The Cochrane Handbook for Systematic Reviews of Interventions was used for quality evaluation, and the meta-analysis was conducted using RevMan 5.3 and Stata 15.1. Results: Thirty-three studies involving 4,098 participants were included. The combination of RYR-containing CCPP, such as Xuezhikang (XZK), Zhibitai (ZBTAI), or Zhibituo (ZBTUO) with statins had a significant effect on the increase in clinical efficacy [RR:1.16, 95%CI (1.13, 1.19), p < 0.00001]. In addition, they also improved blood lipid profile parameters by increasing HDL-C levels [MD:0.21, 95%CI(0.17, 0.25), p < 0.00001], and decreasing TC [MD: 0.60, 95%CI(-0.76, -0.45), p < 0.00001], TG [MD: 0.33, 95%CI(-0.39, -0.26), p < 0.00001] and LDL-C levels [MD: 0.45, 95%CI(-0.54, -0.36), p < 0.00001]. No significant adverse reactions was observed in the RYR-containing CCPPs. Notably, ZBTAI and XZK significantly reduced the incidence of gastrointestinal disturbances and muscular adverse reactions. However, subgroup analyses suggested that the type of CCPPs, dose, and treatment duration might affect the efficacy of RYR-containing CCPPs. Conclusion: RYR-containing CCPPs combined with statins appears to improve lipid profiles and clinical efficacy in patients with dyslipidemia. However, due to the poor quality of the included studies, and some studied showing negative findings was unpublished. The results should be interpreted with caution until further confirmation by well-designed RCTs. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=487402, identifier CRD42023487402.
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OBJECTIVE: Kidney-tonifying formulas are frequently used in clinical practices to enhance follicular development and maturation. This research explored the impacts of the Bushen Tiaojing formula (BSTJF) on the development of mouse preantral follicles in vitro and its relationship with granulosa cells and gonadotropins. METHODS: Preantral follicles were extracted from mice and cultured with or without serum from rats that were previously treated with or without BSTJF. During cultivation, the follicles were monitored for morphological changes and developmental maturation. Exhausted medium was collected every other day for the measurement of progesterone and estradiol (E2) levels by ELISA. Granulosa cells in in-vitro medium were collected on days 8, 10, and 12 and analyzed for determining the expressions of apoptosis-associated genes (Bax, Bcl-2, and Caspase-3). Propagation and apoptosis rates of collected granulosa cells were measured by CCK-8 assay and flow cytometry. RESULTS: Compared with control follicles, follicles cultured with serum from BSTJF-treated rats had a higher survival rate, larger follicle diameter, higher Bcl-2 expression, and lower Bax and Caspase-3 expressions (all P ≤ 0.05). In addition, their granulosa cells presented substantially elevated proliferation (P ≤ 0.05) and a lower rate of apoptosis (P ≤ 0.05) compared with granulosa cells from control follicles. The level of E2 in the culture media of all groups increased slowly in the first 6 days. Subsequently, after formation of the antrum, the levels of E2 and progesterone were enhanced in the medium of follicles cultured with serum from BSTJF-treated rats compared with those in the media of control follicles (all P ≤ 0.05). CONCLUSION: Serum from BSTJF-treated rats facilitated the in vitro development and maturation of mouse follicles by increasing the expression of anti-apoptotic gene Bcl-2, reducing the expressions of pro-apoptotic genes Bax and Caspase-3 as well as the apoptosis of granulosa cells, promoting the proliferation of granulosa cells and increasing the secretion of E2 and progesterone in the cells.
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Curcumin (CUR) possesses the capability to inhibit various inflammatory factors, exert anti-inflammatory effects, and alleviate asthma attacks; however, its hydrophobicity and instability significantly impede its clinical application. In this study, we synthesized CUR-loaded nanoparticles (CUR-NPs) and evaluated their impact on the proliferation, migration, and inflammatory infiltration of mouse airway smooth muscle cells (ASMCs), while investigating their underlying mechanisms. To achieve this objective, ASMCs were isolated from BALB/c mice and subjected to TGF-ß1-induced cell proliferation and migration. Our findings demonstrate that CUR-NPs effectively regulate the release of CUR within cells with superior intracellular uptake compared to free CUR. The CCK-8 assay results indicate that the blank carrier does not exhibit any cytotoxic effects on cells, thus rendering the impact of the carrier itself negligible. The TGF-ß1 group exhibited a significant increase in cell proliferation, whereas treatment with CUR-NPs significantly suppressed TGF-ß1-induced cell proliferation. The findings from both the cell scratch assay and transwell assay demonstrated that TGF-ß1 substantially enhanced cell migration, while CUR-NPs treatment effectively attenuated TGF-ß1-induced cell migration. The Western blot analysis demonstrated a substantial increase in the expression levels of TGF-ß1, p-STAT3, and CTGF in ASMCs following treatment with TGF-ß1 when compared to the control group. Nevertheless, this effect was effectively counteracted upon administration of CUR-NPs. Furthermore, an asthma mouse model was successfully established and CUR-NPs were administered through tail vein injection. The serum levels of TGF-ß1 and the expression levels of TGF-ß1, p-STAT3, and CTGF proteins in the lung tissue of mice in the model group exhibited significant increases compared to those in the control group. However, CUR-NPs treatment effectively attenuated this change. Our research findings suggest that CUR-NPs possess inhibitory effects on ASMC proliferation, migration, and inflammatory infiltration by suppressing activation of the TGF-ß1/p-STAT3/CTGF signaling pathway, thereby facilitating inhibition of airway remodeling.
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Background: Coronary heart disease (CHD) poses a serious threat to public health, and the current medical management still faces significant challenges. Reliable evidence on the efficacy of Shuxuening injection (SXNI) in CHD is still lacking, even though it is widely used in China. Purpose: To evaluate the efficacy of SXNI combination therapy in treating CHD. Methods: A systematic search of eight databases was conducted to identify relevant randomized controlled trials (RCTs) from the inception of each database until June 2023. ROB 2.0, RevMan 5.4, and Stata 15.1 were used for quality evaluation and data analysis. The Grading of Recommendation, Assessment, Development, and Evaluation (GRADE) approach was used to evaluate the quality of evidence. Results: A total of 3,779 participants from 39 studies were included. The results showed SXNI combination therapy increased the clinical efficacy and decreased the frequency and duration of angina. Furthermore, SXNI combination therapy improved cardiac function of patients by decreasing LVEDD, and increased CI, CO, and LVEF. It also improved blood lipid profiles by increasing HDL, decreasing TC, TG, and LDL. The thrombosis factors of patients were also improved by decreasing FIB, PV, HCT, and HS. Moreover, SXNI combination therapy was superior to the conventional treatment in improving CRP levels, increasing ECG efficacy and BNP. However, due to the limited safety information, reliable safety conclusions could not be drawn. Furthermore, the levels of evidence ranged from very low to moderate due to publication bias and heterogeneity. Conclusion: SXNI can effectively improve angina symptoms, clinical efficacy, cardiac function, blood lipid indicators, and thrombosis factors of patients with CHD. However, more multi-center and large-sample studies are needed to confirm the conclusions due to the limitations of this study. Registration https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=399606; Identifier: CRD42023433292.
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Recurrent spontaneous abortion (RSA) is one of the most common complications during pregnancy and seriously affects women's physical and mental health. About 50% of RSA cases are of unknown etiology. Our previous study found that the decidual tissue of patients with unexplained recurrent spontaneous abortion (URSA) had low expression levels of serum and glucocorticoid-induced protein kinase (SGK) 1. Endometrial decidualization is a key link in the early stage of pregnancy and is crucial to the development and maintenance of pregnancy. Decidualization is the proliferation and differentiation of endometrial stromal cells into deciduals, which involves a complex physiological process such as ovarian steroid hormones (estrogen, progesterone, prolactin, etc.), growth factors, and intercellular signaling. The binding of estrogen and its receptor stimulates the synthesis of endometrial deciduating markers prolactin (PRL) and insulin-like growth factor binding protein 1 (IGFBP-1), which mediates the occurrence of decidualization. Among them, SGK1/ENaC is a signaling pathway closely related to decidualization. The purpose of this study was to further investigate the expression of SGK1 and decidualization-related molecules in the decidual tissue of URSA patients and to explore the potential mechanism of SGK1's protective effect in URSA patients and in mouse models. Decidual tissue samples from 30 URSA patients and 30 women who actively terminated pregnancy were collected, and a URSA mouse model was established and treated with dydrogesterone. Expression levels of SGK1 and its signaling pathway-related proteins (p-Nedd4-2, 14-3-3 protein and ENaC-a), estrogen and progesterone receptors (ERß, PR), and decidualization markers (PRLR, IGFBP-1) were assessed. Our study found that SGK1, p-Nedd4-2, 14-3-3 proteins, and ENaC-a expression levels were reduced in the decidual tissue, the SGK1/ENaC signaling pathway was inhibited, and the expression levels of the decidualization markers PRLR and IGFBP-1 were downregulated in the URSA group compared with the controls. Additionally, the concentrations of E2, P, and PRL in the serum of mice were decreased in the URSA group compared with the controls. However, SGK1/ENaC pathway-related proteins, estrogen and progesterone and their receptors, and decidualization-related molecules were upregulated by dydrogesterone. These data suggest that estrogen and progesterone can induce decidualization by activating the SGK1/ENaC signaling pathway; disruption of this pathway can lead to the development of URSA. Dydrogesterone can increase the expression level of SGK1 protein in decidual tissue.
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Aborto Habitual , Aborto Espontáneo , Humanos , Embarazo , Femenino , Ratones , Animales , Progesterona/farmacología , Progesterona/metabolismo , Decidua/metabolismo , Proteína 1 de Unión a Factor de Crecimiento Similar a la Insulina/metabolismo , Aborto Espontáneo/metabolismo , Prolactina/metabolismo , Didrogesterona , Transducción de Señal/fisiología , Estrógenos/metabolismo , Aborto Habitual/metabolismo , Células del Estroma/metabolismoRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Threatened abortion is a common disease among women of childbearing age. Its high incidence rate and unclear etiology, seriously threaten women's physical and mental health. Shoutai Wan (STW) is a traditional Chinese medicine decoction for treating abortion. It has a long history of treating threatened abortion by tonifying the kidney and calming the fetus. However, the mechanism of STW remains unclear. AIM OF STUDY: To study the mechanism and potential benefit of STW in pregnant mice with hydrocortisone and mifepristone-induced threatened abortion. MATERIALS AND METHODS: The STW compounds were identified using gas chromatography-mass spectrometry analysis. STW-H, STW-M, or STW-L was separately given 3 mg/ml, 1.5 mg/ml and 0.75 mg/ml STW in the morning, and 2 mg/ml hydrocortisone in the afternoon from gestation day (D) 1-9 and once with 0.4 mg/kg mifepristone on D10. Didroxyprogesterone (0.1 mg/ml) and equal dose pure water were used to replace STW in didroxyprogesterone (DYD) group and model group respectively. The control group used pure water to replace STW, hydrocortisone, and mifepristone. We performed morphological and histological analyses of the maternal-fetal interface on day 10. RESULTS: The embryo loss rate in the STW-H and DYD groups was lower than that in the model group. Hematoxylin and eosin (HE) staining suggested that the morphology of maternal-fetal interface was improved in the STW-H and DYD groups. Immunohistochemical (IHC), Quantitative Reverse Transcription Polymerase Chain Reactionstaining (qRT-PCR), and Western blot (WB) results indicated that HIF-1α expression in the maternal-fetal interface of the STW-H and DYD groups was higher than that in model group. The activities of HK, PKM, LDH and the concentration of lactic acid in the STW-H and DYD groups were higher than those in model group. Furthermore, the protein and mRNA levels of HK2, PKM2, LDHA, MCT4, and GPR81 were higher in the STW-H and DYD groups than those in the model group. CONCLUSIONS: STW can reduce the pregnancy loss rate by regulating the glycolysis balance at the maternal-fetal interface of kidney deficiency threatened abortion model mice.
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Aborto Inducido , Aborto Espontáneo , Amenaza de Aborto , Embarazo , Humanos , Ratones , Femenino , Animales , Amenaza de Aborto/tratamiento farmacológico , Mifepristona/farmacología , HidrocortisonaRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Kunling Wan (KW) is a traditional Chinese medicine that is principally used for kidney deficiency, qi stagnation, and blood stasis, which are basic syndromes of infertility in China. KW can improve ovarian follicular development, ovarian function, and endometrial receptivity, which lead to improving pregnancy outcomes. Repeated controlled ovarian hyperstimulation (COH) reduces oocyte quality and results in a lower pregnancy rate. Whether KW has the potential to improve oocyte quality reduced by repeated COH has yet to be determined. AIMS OF THE STUDY: The aim of this study wwas to evaluate the effect of KW on oocyte quality after damage due to repeated COH, and to investigate the mechanism(s) underlying the antioxidative protection of oocytes by mitochondria. MATERIALS AND METHODS: Female Kunming mice were randomly divided into four groups: normal group, model (repeated COH) group, KW group, and N-acetylcysteine (NAC) group. We observed the morphology and quality of mitochondria, level of reactive oxygen species (ROS), and antioxidant enzymes activity of each group. Oocytes were treated with H2O2 and KW-containing serum, and we determined the antioxidant effects of KW on H2O2-treated oocytes and the mechanism involved in the regulation of Nrf2 in reducing oxidative damage. RESULTS: Our results revealed that repeated COH caused oxidative damage and impaired oocyte mitochondrial function and structure, resulting in poor oocyte quality. KW pretreatment reduced oxidative damage by inhibiting ROS production and improving mitochondrial structure and function, thereby enhancing overall oocyte quality. In response to H2O2, KW activated the PKC/Keap1/Nrf2-signaling pathway and promoted the translocation of Nrf2 from the cytoplasm to the nucleus, which activated the expression of SOD and GSH-Px, and removed the excess ROS that caused the initial mitochondrial damage. CONCLUSIONS: KW improved oocyte quality perturbed by repeated COH via reducing oxidative effects and improving mitochondrial function. The mechanism may be related to regulation of the PKC/Keap1/Nrf2 pathway in removing excess ROS.
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Peróxido de Hidrógeno , Factor 2 Relacionado con NF-E2 , Animales , Femenino , Ratones , Embarazo , Antioxidantes/farmacología , Antioxidantes/metabolismo , Peróxido de Hidrógeno/metabolismo , Proteína 1 Asociada A ECH Tipo Kelch/metabolismo , Factor 2 Relacionado con NF-E2/metabolismo , Oocitos/metabolismo , Estrés Oxidativo , Especies Reactivas de Oxígeno/metabolismoRESUMEN
Cold coagulation and blood stasis (CCBS) syndrome is one of the common traditional Chinese medicine (TCM) syndromes of gynecological diseases. However, the molecular mechanism of CCBS syndrome is still unclear. Thus, there is a need to reveal the occurrence and regulation mechanism of CCBS syndrome, in order to provide a theoretical basis for the treatment of CCBS syndrome in gynecological diseases. The plasma proteins in primary dysmenorrhea (PD) patients with CCBS syndrome, endometriosis (EMS) patients with CCBS syndrome, and healthy women were screened using Label-free quantitative proteomics. Based on the TCM theory of "same TCM syndrome in different diseases," the differentially expressed proteins (DEPs) identified in each group were subjected to intersection mapping to obtain common DEPs in CCBS syndrome. The DEPs of gynecological CCBS syndrome in the intersection part were again cross-mapped with the DEPs of gynecological CCBS syndrome obtained by the research group according to the TCM theory of "different TCM syndromes in same disease" theory in the early stage, so as to obtain the DEPs of gynecological CCBS syndrome that were shared by the two parts. The common DEPs were subjected to bioinformatics analysis, and were verified by enzyme-linked immunosorbent assay (ELISA). A total of 67 common DEPs were identified in CCBS syndrome, of which 33 DEPs were upregulated and 34 DEPs were downregulated. The functional classification of DEPs involved in metabolic process, energy production and conversion, immune system process, antioxidant activity, response to stimulus, and biological adhesion. The subcellular location mainly located in the cytoplasm, nucleus, and extracellular. Gene ontology (GO) enrichment analysis showed that the upregulated DEPs mainly concentrated in lipid transport, cell migration, and inflammatory reaction, and the downregulated DEPs mostly related to cell junction, metabolism, and energy response. Protein domain enrichment analysis and clustering analysis revealed that the DEPs mainly related to cell proliferation and differentiation, cell morphology, metabolism, and immunity. The Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis clustering analysis showed that the upregulated DEPs were involved in inflammation and oxidative damage, while the downregulated DEPs were involved in inflammation, cell adhesion, cell apoptosis, and metabolism. The results of ELISA showed significantly increased levels of Cell surface glycoprotein MUC18 (MCAM) and Apolipoprotein C1 (APOC1), and significantly decreased levels of Vasodilator-stimulated phosphoprotein (VASP), Fatty acid-binding protein 5 (FABP5), and Vinculin (VCL) in patients with CCBS syndrome compared with healthy women. We speculated that cold evil may affect the immune process, inflammatory response, metabolic process, energy production and conversion, oxidative damage, endothelial cell dysfunction, and other differential proteins expression to cause CCBS syndrome in gynecological diseases.
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Estrés Oxidativo , Proteómica , Humanos , Femenino , Apoptosis , Adhesión Celular , Inflamación , Proteínas de Unión a Ácidos GrasosRESUMEN
The effects of repeated controlled ovarian stimulation (COS) on the female reproductive system are still controversial. This study investigated the effects of repeated COS on the ovaries and uterus of mice and its possible mechanism. Female ICR (Institute of Cancer Research) mice were subjected to the COS using pregnant mare serum gonadotropin (PMSG) and human chorionic gonadotropin (hCG) for 1, 3, 5, and 7 cycles. Serum hormone levels, reactive oxidative stress (ROS), 8-hydroxy-2'-deoxyguanosine (8-OHdG), total antioxidant capacity (T-AOC), and superoxide dismutase (SOD) in the mouse ovary and uterus were analyzed by ELISA. The morphology of the ovary and endometrium, ovarian apoptosis, and expressions of the vascular endothelial growth factor (VEGF), leukemia inhibitory factor (LIF), PI3K, AKT, Bax, and Bcl-2 in the ovarian and uterine tissues were tested by hematoxylin-eosin (HE) staining, immunohistochemistry, and western blot. The results showed that repeated COS significantly decreased the hormone level (estradiol, progesterone and anti-Müllerian hormone), high-quality of the MII oocyte ratio, oocyte and embryo number, antioxidant capacity (T-AOC, SOD activity), and the protein level of Bcl-2, LIF, and VEGF, but increased the oxidative damage (ROS, 8-OHdG content), embryo fragment ratio, and expression of pro-apoptotic protein Bax. In addition, the expressions of p-PI3K and p-AKT also decreased with the increase of COS cycle. In conclusion, repeated COS causes ovarian and uterus damage possibly through the PI3K/AKT signaling pathway, and this finding may provide some experimental basis for guiding clinical treatment.
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Proteínas Proto-Oncogénicas c-akt , Factor A de Crecimiento Endotelial Vascular , Embarazo , Animales , Ratones , Femenino , Humanos , Fosfatidilinositol 3-Quinasas , Antioxidantes , Especies Reactivas de Oxígeno , Proteína X Asociada a bcl-2 , Ratones Endogámicos ICR , Progesterona , Útero , Transducción de Señal , Inducción de la Ovulación/efectos adversos , Superóxido DismutasaRESUMEN
[This corrects the article DOI: 10.1016/j.isci.2022.104509.].
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Quinoa (Chenopodium quinoa Willd.) contains various physiologically active substances, including vitamins, polyphenols, flavonoids, phytosterols, and saponins. Research showed that saponins were the protective substances in the outer layer of quinoa seeds to defend against microbes, herbivores, and insects. Because the aglycones of quinoa saponins are triterpenoids, they are called triterpenoid saponins (TSs). In addition, the presence of TS imparted bitterness in quinoa and resulted in anticancer and anti-inflammatory effects. In this study, the seeds of low-saponin quinoa, NT376-2 (N), and high-saponin quinoa, B-12071(B), at 30 and 60 days after flowering (DAF) were used to measure the TS content and evaluated for their transcriptomic and metabolomic profiles. The amounts of TS were found to significantly differ between all possible comparisons: N and B at 30 DAF (N1_vs_B1), N and B at 60 DAF (N2_vs_B2), N at 30 DAF and 60 DAF (N1_vs_N2), and B at 30 DAF and 60 DAF (B1_vs_B2). RNA sequencing (RNA-seq) was used to screen differentially expressed genes (DEGs) and revealed 14,703 upregulated DEGs and 26,267 downregulated DEGs in the four comparison groups. The 311 overlapping DEGs found in the four comparisons were used for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses to screen for DEGs related to TS biosynthesis in quinoa. Metabolomics analysis identified acetyl-CoA, 1-hydroxy-2-methyl-2-butenyl-4-diphosphate, farnesal, and (S)-2,3-epoxysqualene as the key differentially accumulated metabolites (DAMs). Transcriptomics-metabolomics joint analysis showed that triterpenoid biosynthesis and terpenoid backbone biosynthesis were the enriched pathways of TS biosynthesis; farnesal were the key DAMs shared in the four comparison groups and associated with 10 key candidate DEGs related to TS biosynthesis in quinoa. These results provided important references for in-depth research on the metabolic mechanism of TS in quinoa.
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Endometriosis has been found to be closely related to autophagy. This study aimed to elucidate the possible mechanism of Bushen Wenyang Huayu Decoction (BWHD) in treating endometriosis (EMs) by targeting TLR4/NF-κB-mediated autophagy. Autologous grafting was used to generate the EMs model in rats. Once the model was developed, BWHD high-dose and low-dose groups received intragastric administration of BWHD, and the gestrinone group served as a positive control. Immunofluorescence labeling and Western blotting were used for the protein expression of toll-like receptor 4 (TLR4), nuclear transcription factor-κB (NF-κB), Beclin-1, and selective autophagy connector protein P62 (P62). Quantitative real-time polymerase chain reaction (qRT-PCR) was used to analyze mRNA levels of TLR4, NF-κB, Beclin-1, and P62. We found that BWHD significantly reduced the size of ectopic lesions in rats with EMs, regulated reproductive hormone levels, and alleviated the cell autophagy level. It suggested that BWHD could be an effective treatment of EMs by targeting TLR4/NF-κB signaling pathway.
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Eucommiae Folium (EF), a traditional Chinese medicine, has been used to treat secondary hypertension, including renal hypertension and salt-sensitive hypertension, as well as hypertension caused by thoracic aortic endothelial dysfunction, a high-fat diet, and oxidized low-density lipoprotein. The antihypertensive components of EF are divided into four categories: flavonoids, iridoids, lignans, and phenylpropanoids, such as chlorogenic acid, geniposide acid and pinoresinol diglucoside. EF regulates the occurrence and development of hypertension by regulating biological processes, such as inhibiting inflammation, regulating the nitric oxide synthase pathway, reducing oxidative stress levels, regulating endothelial vasoactive factors, and lowering blood pressure. However, its molecular antihypertensive mechanisms are still unclear and require further investigation. In this review, by consulting the relevant literature on the antihypertensive effects of EF and using network pharmacology, we summarized the active ingredients and pharmacological mechanisms of EF in the treatment of hypertension to clarify how EF is associated with secondary hypertension, the related components, and underlying mechanisms. The results of the network pharmacology analysis indicated that EF treats hypertension through a multi-component, multi-target and multi-pathway mechanism. In particular, we discussed the role of EF targets in the treatment of hypertension, including epithelial sodium channel, heat shock protein70, rho-associated protein kinase 1, catalase, and superoxide dismutase. The relevant signal transduction pathways, the ras homolog family member A (RhoA)/Rho-associated protein kinase (ROCK) and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase/eNOS/NO/Ca2+ pathways, are also discussed.
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A series of oxazinyl flavonoids were synthesized on the basis of flavone. The structures of all target compounds were characterized by 1H NMR, 13C NMR, and HRMS. The effect of the different substituent on the N-position of oxazinyl flavonoids against tobacco mosaic virus (TMV) activities and plant pathogen activities was systematically investigated. In vivo anti-TMV activity showed that most of the compounds showed moderate-to-excellent antiviral activities against TMV at 500 µg/mL. Compounds 6b, 6d, 6j-6k, and 6n-6q showed better antiviral activities than ribavirin (a commercially available antiviral agent) and apigenin. In particular, compounds 6n and 6p even displayed slightly higher activities than ningnanmycin, which were expected to become new antiviral candidates. Antiviral mechanism research by molecular docking exhibited that compounds 6n and 6p could interact with TMV CP and inhibit virus assembly. Then, the antifungal activities of these compounds against six kinds of plant pathogenic fungi were tested, and the results showed that these oxazinyl flavonoids had broad-spectrum fungicidal activities. Compounds 6h exhibited antifungal activity of up to 91% against Physalospora piricola and might become a candidate drug for new fungicides.
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Alcaloides , Fungicidas Industriales , Virus del Mosaico del Tabaco , Antivirales/química , Ribavirina/farmacología , Fungicidas Industriales/farmacología , Antifúngicos/farmacología , Relación Estructura-Actividad , Flavonoides/farmacología , Simulación del Acoplamiento Molecular , Apigenina/farmacología , Estructura Molecular , Alcaloides/química , Hongos , Diseño de FármacosRESUMEN
Morroniside is the main ingredient of Cornus officinalis and has a variety of biological activities including antioxidative effects. Ovarian granulosa cells (GCs) are responsible for regulating the development and atresia of follicles, which are susceptible to oxidative stress. In this study, we determined whether morroniside can inhibit the oxidative stress of GCs induced by hydrogen peroxide (H2O2), leading to improved oocyte quality. The oxidative damage and apoptosis of ovarian GCs cultured in vitro were induced by the addition of H2O2. After pretreatment with morroniside, the levels of ROS, MDA, and 8-OHdG in ovarian GCs were significantly decreased. Morroniside significantly upregulated p-Nrf2 and promoted the nuclear translocation of Nrf2, which transcriptionally activated antioxidant SOD and NQO1. In addition, morroniside significantly regulated the levels of apoptosis-related proteins Bax, Bcl-2, cleaved caspase-9, and cleaved caspase-3 via the p38 and JNK pathways. These results suggest that morroniside can reduce the oxidative damage and apoptosis of ovarian GCs induced by H2O2.
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BACKGROUND: Chlamydia pneumoniae (Cpn) is one of the most common respiratory pathogens in children and adults. It is characterized as an obligate intracellular parasite. Peripheral blood monocytes (PBMC), lymphocytes, and macrophages are involved in spreading chlamydia infection to extrapulmonary organs indicating that Cpn infection can cause systematic symptoms in vivo via blood transmission. METHODS: This review summarizes the mechanisms of Cpn infection in host cells, the immune response of the body, and the relationship between Cpn infection and some chronic diseases. RESULTS: Cpn participation in extrapulmonary chronic diseases has been proven owing to the presence of Cpn DNA in AS plaque, nerve tissues, and synovium tissues of the joints. CONCLUSIONS: Cpn infection is related to the development of chronic diseases such as atherosclerosis, Alzheimer's Disease (AD), and reactive arthritis through in vivo and in vitro experiments.
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Infecciones por Chlamydia , Infecciones por Chlamydophila , Chlamydophila pneumoniae , Sepsis , Adulto , Niño , Infecciones por Chlamydia/complicaciones , Infecciones por Chlamydophila/complicaciones , Infecciones por Chlamydophila/diagnóstico , Enfermedad Crónica , Humanos , Leucocitos MononuclearesRESUMEN
Purpose: Severe mycoplasma pneumoniae (MP) pneumonia can cause bronchiolitis obliterans (BO). In order to improve the prognosis of BO, it is necessary to grasp the clinical characteristics and risk factors of BO after severe MP pneumonia and intervene as soon as possible. Patients and Methods: This study retrospectively analyzed the clinical data of 110 patients with severe MP pneumonia, and divided them into BO group (22 cases) and non-BO group (88 cases). The clinical characteristics of BO group were analyzed, and the clinical data of two groups were compared to identify the risk factors of BO. Results: At the time of diagnosis, all BO patients had symptoms of cough and wheezing, and 10 (45.45%) had decreased exercise intolerance. Lung function showed moderate to severe obstructive ventilatory dysfunction, high-resolution computed tomography (HRCT) showed mosaic perfusion patterns. Multivariate binomial regression analysis showed that higher levels of serum lactate dehydrogenase (LDH) and hypoxemia were independent risk factors for BO after severe MP pneumonia. Conclusion: Higher levels of serum LDH and hypoxemia were independent risk factors for BO after severe MP pneumonia. For patients with risk factors, clinicians should regular follow-up for early diagnosis and intervention of BO.
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[This corrects the article DOI: 10.3389/fpls.2022.818345.].
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Endometrial angiogenesis is necessary for good endometrial receptivity. Krüppel-like factor 4 (KLF4) is a transcription factor that is essential for regulating angiogenesis. Here we found that vascular endothelial growth factor A (VEGFA) can form a positive feedback loop with KLF4 to promote the proliferation and migration of human endometrial microvascular endothelial cells (HEMECs) and inhibit cell apoptosis. General control non-derepressible 5 (GCN5) is also time-dependent on VEGFA and participates in the KLF4-VEGFA loop. In addition, we found that GCN5 is a succinyltransferase that modulates the succinylation of histones and nonhistones. GCN5 interacts with KLF4 and is recruited to the KLF4-binding site of the VEGFA promoter to succinylate H3K79, which initiates gene transcription epigenetically. For nonhistones, GCN5 succinylates KLF4 that is activated by ERK signaling in HEMECs treated with VEGFA to increase its transcription activity. These results demonstrate KLF4-VEGFA positive feedback loop is regulated by epigenetics, which contributes to endometrial angiogenesis.