The therapeutic potential of Ziziphi Spinosae Semen and Polygalae Radix in insomnia management: Insights from gut microbiota and serum metabolomics techniques.

ETHNOPHARMACOLOGICAL RELEVANCE: Ziziphi Spinosae Semen and Polygalae Radix (ZSS-PR) constitute a traditional Chinese herbal combination with notable applications in clinical and experimental settings due to their evident sedative and calming effects. Aligned with traditional Chinese medicine principles, Ziziphi Spinosae Semen supports cardiovascular health, nourishes the liver, and induces mental tranquillity. Simultaneously, Polygalae Radix elicits calming effects, fosters clear thinking, and reinstates proper coordination between the heart and kidneys. ZSS-PR is commonly employed as a therapeutic intervention for various insomnia types, demonstrating distinct clinical efficacy. Our previous study findings provide evidence that ZSS-PR administration significantly reduces sleep onset latency, increases overall sleep duration, and improves abnormal neurotransmitter levels in a murine insomnia model. AIM OF STUDY: This investigation aimed to scrutinize the intrinsic regulatory mechanism of ZSS-PR in managing insomnia using gut microbiota and serum metabolomics techniques. MATERIALS AND METHODS: Mice were given DL-4-Chlorophenylalanine to induce insomnia and then treated with ZSS-PR. The open-field test assessed the animals' spontaneous activity. Concentrations of neurotransmitters, endocrine hormones, and cytokines in the duodenum were measured using enzyme linked immunosorbent assay, and brain histopathology was evaluated with H&E staining. The impact of ZSS-PR on the metabolic profile was examined by liquid chromatography couped to high resolution mass spectrometry, and 16S rDNA sequencing was used to study the influence of ZSS-PR on the gut microbiota. Additionally, the content of short-chain fatty acids (SCFAs) was analyzed by GC-MS. Finally, correlation analysis investigated relationships between biochemical markers, metabolites, SCFAs, and gut microbiota. RESULTS: ZSS-PR treatment significantly increased movement time and distance in mice with insomnia and improved pathological impairments in the cerebral cortex and hippocampus. It also restored abnormal levels of biochemical markers in the gut of insomnia-afflicted mice, including 5-hydroxytryptamine, dopamine, gastrin, melatonin, tumour necrosis factor-α, and interleukin-1ß. Metabolomics findings showed that ZSS-PR had a significant restorative effect on 15 endogenous metabolites in mice with insomnia. Furthermore, ZSS-PR primarily influenced five metabolic pathways, such as phenylalanine, tyrosine, and tryptophan biosynthesis, glutamine, and glutamate metabolism. Additionally, gut microbiota analysis revealed notable alterations in both diversity and microbial composition after ZSS-PR treatment. These changes were primarily attributed to the relative abundances of microbiota, including Firmicutes, Bacteroidota, Fusobacteriota, Muribaculaceae_unclassified, and Ligilactobacillus. The results of SCFAs analysis demonstrated that ZSS-PR effectively restored abnormal levels of acetic acid, propionic acid, isobutyric acid, butyric acid, isovaleric acid, and valeric acid in insomniac mice. Subsequent correlation analysis revealed that microbiota show obvious correlations with both biochemical markers and metabolites. CONCLUSIONS: The results provide compelling evidence that ZSS-PR effectively mitigates abnormal activity, reduces cerebral pathological changes, and restores abnormal levels of neurotransmitters, endocrine hormones, and cytokines in mice with insomnia. The underlying mechanism is intricately linked to the modulation of gut microbiota and endogenous metabolic pathways.

Pumpkin Leaf Extract Crop Waste as a New Degradable and Environmentally Friendly Corrosion Inhibitor.

The pumpkin leaf was extracted by the decoction method, and it was used as an eco-friendly, nontoxic inhibitor of copper in 0.5 M H2SO4 corrosion media. To evaluate the composition and protective capacity of the pumpkin leaf extract, Fourier infrared spectroscopy, electrochemical testing, XPS, AFM, and SEM were employed. The results showed that the pumpkin leaf extract (PLE) is an effective cathode corrosion inhibitor, exhibiting exceptional protection for copper within a specific temperature range. The corrosion inhibition efficiency of the PLE against copper reached 89.98% when the concentration of the PLE reached 800 mg/L. Furthermore, when the temperature and soaking time increased, the corrosion protection efficiency of 800 mg/L PLE on copper consistently remained above 85%. Analysis of the morphology also indicated that the PLE possesses equally effective protection for copper at different temperatures. Furthermore, XPS analysis reveals that the PLE molecules are indeed adsorbed to form an adsorption film, which is consistent with Langmuir monolayer adsorption. Molecular dynamics simulations and quantum chemical calculations were conducted on the main components of the PLE.

Interaction of air pollution and meteorological factors on IVF outcomes: A multicenter study in China.

BACKGROUND: Previous studies revealed associations between air-pollutant exposure and in vitro fertilization (IVF) outcomes. However, modification effects of air pollution on IVF outcomes by meteorological conditions remain elusive. METHODS: This multicenter retrospective cohort study included 15,217 women from five northern Chinese cities during 2015-2020. Daily average concentrations of air pollutants (PM2.5, PM10, O3, NO2, SO2, and CO) and meteorological factors (temperature, relative humidity, wind speed, and sunshine duration) during different exposure windows were calculated as individual approximate exposure. Generalized estimating equations models and stratified analyses were conducted to assess the associations of air pollution and meteorological conditions with IVF outcomes and estimate potential interactions. RESULTS: Positive associations of wind speed and sunshine duration with pregnancy outcomes were detected. In addition, we observed that embryo transfer in spring and summer had a higher likelihood to achieve a live birth compared with winter. Exposure to PM2.5, SO2, and O3 was adversely correlated with pregnancy outcomes in fresh IVF cycles, and the associations were modified by air temperature, relative humidity, and wind speed. The inverse associations of PM2.5 and SO2 exposure with biochemical pregnancy were stronger at lower temperatures and humidity. Negative associations of PM2.5 with clinical pregnancy were only significant at lower temperatures and wind speeds. Moreover, the effects of O3 on live birth were enhanced by higher wind speed. CONCLUSIONS: Our results suggested that the associations between air-pollutant exposure and IVF outcomes were modified by meteorological conditions, especially temperature and wind speed. Women undergoing IVF treatment should be advised to reduce outdoor time when the air quality was poor, particularly at lower temperatures.

Poor ovarian response is associated with air pollutants: A multicentre study in China.

BACKGROUND: Human evidence on the association between air pollution and ovarian response is scarce. Poor ovarian response (POR) with an incidence of 5-35% is a tricky problem in IVF treatment. METHODS: In this large-scale multicentre study, we included 2186 women with POR (< 4 oocytes retrieved) and 7033 women with a normal ovarian response (10-15 oocytes retrieved), who underwent their first in vitro fertilization treatment in five cities in northern China during 2015-2020. Average concentrations of six air pollutants (PM2.5, PM10, O3, NO2, CO, and SO2) during different exposure windows (5 days, 1, 3, 6, and 12 months) before oocyte pick up (OPU) were calculated using data from the air monitoring station nearest to the residential site as approximate individual exposure. Logistic regression models were employed to assess the association between exposure to air pollutants and the risk of POR. Stratification analyses were conducted based on female age. Sensitivity analyses were performed in poor responders identified by Bologna criteria and women with unexpected POR. FINDINGS: We detected that increased SO2 exposure during all exposure windows before OPU was associated with a higher risk of POR, especially for women ≤ 30 years old. In the stratified analysis, the effect sizes were larger for the unexpected poor ovarian response. INTERPRETATION: The findings provide human evidence for adverse effects of exposure to ambient air pollutants on ovarian response and underscore the need to reduce ambient air pollution exposure in women of reproductive age to protect human fertility. FUNDING: This study was granted from the National Key Research and Development Program (2018YFC1004203), the Major Special Construction Plan for Discipline Construction Project of China Medical University (3110118033), the Shengjing Freelance Researcher Plan of Shengjing Hospital of China Medical University, and the National Natural Science Foundation of China (82071601), the Central Government Special Fund for Local Science and Technology Development (2020JH6/10500006).

The Chemical Constituents of Diaphragma Juglandis Fructus and Their Inhibitory Effect on α-Glucosidase Activity.

In our current investigation, 37 constituents (1-37), including 11 megastigmanes (1-11), 17 flavonoids (12-28) and 9 phenylpropanoids (29-37), were isolated from a 70%-EtOH extract of Diaphragma juglandis Fructus. Among them, compounds 1-3, 12 and 29 were new compounds and their structures were elucidated on the basis of physicochemical evidence and meticulous spectroscopic analysis (NMR, HRESIMS and CD). Compounds 13, 16, 21 and 28 showed moderate inhibitory effect on α-glycosidase inhibitory activities, with IC50 values being in the range of 29.47-54.82 µM and stronger than the positive control (acarbose, 60.01 ± 4.82 µM).

Effects of Dangshen Yuanzhi Powder on learning ability and gut microflora in rats with memory disorder.

ETHNOPHARMACOLOGICAL RELEVANCE: Yuanzhi Powder is a commonly used traditional Chinese medical formulae for its potency in enhancing memory and learning. In clinical practice, Yuanzhi Powder is a classic formula in TCM to treat amnesia of the type "deficiency of Qi, turbid phlegm harasses the head and eyes, and stagnation of phlegm converting into the fire". Our previous study showed that Yuanzhi Power, used together with Codonopsis Radix (Dangshen Yuanzhi Power, DYP), could improve learning and memory ability in animals with memory disorder (MD) and its efficacy is superior or equivalent to that of the Yuanzhi Power. AIM OF STUDY: This study aimed to explore the regulatory mechanism of DYP through the "bacteria-gut-brain axis". MATERIALS AND METHODS: The SD rats were divided randomly into control, model, positive, DYP-L, and DYP-H groups. Except for the control group, the rats were intraperitoneally injected with D-Gal (400 mg/kg) and gavaged with aluminum chloride (200 mg/kg) every day for 50 days. The rats in the DYP group were gavaged with DYP (6.67 and 13.34 g/kg, respectively) from the 15th day, once a day. The rats in the positive group were similarly administrated with piracetam (0.5 g/kg). The rats' bodyweight was recorded from the 16th day. The learning and memory ability of animals was tested by Morris water maze. The levels of MCP-1, NF-L, NSE, and TNF-α in serum were determined by Elisa kit, while the histopathology of duodenum and colon tissues was examined by H & E staining. The diversity of intestinal flora was sequenced and analyzed. In order to reveal the role of intestinal flora in DYP treatment of MD, the intestinal flora composition and the correlation analysis of intestinal flora and the above biochemical indexes were investigated. The intestinal flora function and biological metabolic pathways were predicted and analyzed by the KEGG database. RESULTS: The MD animals' learning and spatial memory ability decreased significantly, compared with the normal group, accompanied by weight increase and intestinal flora disorder. DYP can improve the learning and memory ability of MD animals, and its efficacy may exert through the following ways: (i) callback the abnormal biochemical indexes of MCP-1, NF-L, NSE, and TNF-α; (ii) decreasing the relative ratio of Firmicutes/Bacteroidetes and repairing the pathology of MD animal intestinal mucosa; and (iii) the regulation of DYP on biochemical blood indexes of MD animals was significantly correlated with the regulation of intestinal flora; (iv) DYP rats showed a strong correlation between cognitive ability improvement and bodyweight loss; (v) besides, DYP could also regulate the metabolic pathways of carbohydrate, amino acid, nucleotide, and energy by affecting related biological functions. CONCLUSIONS: The results supported that DYP can improve MD animals' learning and memory ability by restoring the intestinal flora disorder and callback the abnormal biochemical indexes in serum, closely related to the "bacteria-gut-brain axis".

Prolonged Cryopreservation Negatively Affects Embryo Transfer Outcomes Following the Elective Freeze-All Strategy: A Multicenter Retrospective Study.

Background: With the development of embryo freezing and warming technology, frozen-thawed embryo transfer (FET) has been widely utilized. However, studies investigating the association between cryopreservation duration and FET outcomes are limited and controversial, and previous studies did not conduct stratification analyses based on demographic or clinical characteristics. Methods: This multicenter retrospective study included 17,826 women who underwent their first FET following the freeze-all strategy during the period from January 2014 to December 2018. Duration of cryopreservation was categorized into five groups: 3-8 weeks, 8-12 weeks, 12-26 weeks, 26-52 weeks, and >52 weeks. Modified Poisson regression and multivariate logistic regression were used to assess the association between cryostorage time of vitrified embryos and transfer outcomes. Moreover, further stratification analyses were performed according to variables with p <0.05 in multivariate models. Results: In this large multicenter study, we observed that storage duration was inversely associated with the possibility of pregnancy and live birth (p <0.001), but not with the risk of ectopic pregnancy and miscarriage. Stratification analyses based on maternal age, the number of oocytes retrieved, and condition of embryo transferred indicated that the inverse correlation was significant in the subpopulation with characteristics: (1) less than 40 years old, (2) more than 3 oocytes retrieved, and (3) only high-quality blastocysts transferred. Conclusion: The results of this large, multicenter, retrospective study suggested that prolonged cryopreservation was inversely associated with the probability of pregnancy and live birth. Therefore, for patients who adopt a freeze-all strategy, early FET might achieve a better outcome.

Association between exposure to ambient air pollutants and the outcomes of in vitro fertilization treatment: A multicenter retrospective study.

BACKGROUND: Exposure to ambient air pollution has been reported to be inversely correlated with human reproductive health. However, the results of previous studies exploring the association between air pollution and in vitro fertilization (IVF) outcomes are conflicting, and further research is needed to clarify this association. OBJECTIVES: This study aimed to investigate the associations between exposure to air pollutants and IVF outcomes. METHODS: We conducted a multicenter retrospective cohort study involving 20,835 patients from four cities in Northern China, contributing to 11,787 fresh embryo transfer cycles, 9050 freeze-all cycles, and 17,676 frozen-thawed embryo transfer (FET) cycles during 2014-2018. We calculated the daily average concentrations of six criteria air pollutants (PM2.5, PM10, O3, NO2, CO, and SO2) during different exposure windows in IVF treatment timeline using data from the air monitoring station nearest to the residential site as approximate individual exposure. Generalized estimation equation models were used to assess the association between air pollution exposure and IVF outcomes. RESULTS: Exposure to O3, NO2, and CO during most exposure windows in fresh embryo transfer cycles were correlated with lower possibilities of biochemical pregnancy, clinical pregnancy, and live birth. An inverse association of exposure to O3 and SO2 with pregnancy outcomes was observed in FET cycles. In addition, we found a significant association of exposure to air pollutants with a higher risk of ectopic pregnancy and lower oocyte yield. CONCLUSIONS: Our study provided large-scale human evidence of the association between air pollution and adverse human reproductive outcomes in the population opting for IVF. Thus, exposure to air pollutants in the population opting for IVF should be limited to improve treatment outcomes.

Perinatal and maternal outcomes after frozen versus fresh embryo transfer cycles in women of advanced maternal age.

OBJECTIVE: The delay of childbearing in women has become a worldwide issue in recent decades. The application of assisted reproductive technology in women of advanced maternal age (AMA) is increasing. Evidence on the safety and outcomes of frozen embryo transfer (FET) compared with fresh embryo transfer (ET) in AMA women is still lacking. Therefore, the objective of the present study was to compare perinatal and maternal outcomes after autologous FET and fresh ET cycles in women of AMA. STUDY DESIGN: A retrospective study of 1663 FET and 3964 fresh ET cycles in reproductive medical centers from 2009 to 2014. Women who aged ≥35 years and had clinical pregnancies after autologous frozen or fresh ET were included. The main perinatal outcomes included birth weight, gestational age, rates of preterm birth, macrosomia, low birth weight (LBW), and very low birth weight. The main maternal outcomes included rates of hypertensive disorders of pregnancy, gestational diabetes mellitus, and preterm premature rupture of the membranes. RESULTS: Women who underwent FET had an increased risk of hypertensive disorders of pregnancy [1.1 % vs. 0.4 %, adjusted OR (95 % CI): 2.76 (1.39-5.51); p = 0.004]. Singletons born after FET had significantly higher mean birth weight (3388.78 ± 538.47 vs. 3316.19 ± 549.08; p = 0.001). Furthermore, increased risk of macrosomia [13.5 % vs. 10.4 %, adjusted OR (95 % CI): 1.35 (1.07-1.71); p = 0.013] and decreased risk of LBW [3.6 % vs. 5.3 %, adjusted OR (95 % CI): 0.67 (0.45-1.00); p = 0.048] were found in singletons born after FET. CONCLUSIONS: Perinatal risks of AMA patients are higher in FET than in fresh ET, including higher birth weight, risks of macrosomia in singleton births, and hypertensive disorders of pregnancy.

Dehydrocorydaline Accounts the Majority of Anti-Inflammatory Property of Corydalis Rhizoma in Cultured Macrophage.

Corydalis Rhizoma (CR) is a commonly used traditional Chinese medicine for its potency in activating blood circulation and analgesia. In clinic, CR extracts or components are commonly used in the treatment of myocardial ischemia, rheumatism, and dysmenorrhea with different types of inflammation. However, due to different mechanism of pain and inflammation, the anti-inflammatory property of CR has not been fully revealed. Here, the major chromatographic peaks of CR extracts in different extracting solvents were identified, and the anti-inflammatory activities of CR extracts and its major alkaloids were evaluated in LPS-treated macrophages by determining expressions of proinflammatory cytokines, IκBα and NF-κB. The most abundant alkaloid in CR extract was dehydrocorydaline, having >50% of total alkaloids. Besides, the anti-inflammatory activities of dehydrocorydaline and its related analogues were demonstrated. The anti-inflammatory roles were revealed in LPS-treated cultured macrophages, including (i) inhibiting proinflammatory cytokines release, for example, TNF-α, IL-6; (ii) suppressing mRNA expressions of proinflammatory cytokines; (iii) promoting IκBα expression and suppressing activation of NF-κB transcriptional element; and (iv) reducing the nuclear translocation of NF-κB. The results supported that dehydrocorydaline was the major alkaloid in CR extract, which, together with its analogous, accounted the anti-inflammatory property of CR.