Replacement of Loops at the Entrance of the Active Pocket of Streptococcus thermophilus 4,6-α-Glucanotransferase Changes Its Catalytic Activity and Product Specificity.

To explore the roles of loops around active pocket in the reuteran type 4,6-α-glucanotransferase (StGtfB) from S. thermophilus, they were individually or simultaneously replaced with those of an isomalto/maltopolysaccharides type 4,6-α-glucanotransferase from L. reuteri. StGtfB with the replaced loops A1, A2 (A1A2) and A1, A2, B (A1A2B), respectively, showed 1.41- and 0.83-fold activities of StGtfB. Two mutants reduced crystallinity and increased starch disorder at 2, 4, and 8 U/g more than StGtfB and increased DP ≤ 5 short branches of starch by 38.01% at 2 U/g, much more than StGtfB by 4.24%. A1A2B modified starches had the lowest retrogradation over 14 days. A1A2 modified starches had the highest percentage of slowly digestible fractions, ranging from 40.32% to 43.34%. StGtfB and its mutants bind substrates by hydrogen bonding and van der Waals forces at their nonidentical amino acid residues, suggesting that loop replacement leads to a different conformation and changes activity and product structure.

Potential of Lactobacillus plantarum A56 in relieving food allergy through immunoregulation, antioxidation, and reshaping intestinal microbiota.

Food allergy is an abnormal immune reaction triggered by food protein antigens. Relevant studies have suggested that probiotic supplementation was with the potential to alleviate food allergy. This study aimed to explore the effects of Lactobacillus plantarum A56 on the alleviation of ovalbumin (OVA)-induced food allergy via immunomodulatory function, antioxidation, and modification of intestinal microbiota. Balb/c mice were sensitized with OVA (20 µg/mouse) by intraperitoneal injection for 3 weeks and accompanied by oral administration of L. plantarum A56 (109 CFU/mL), subsequently with orally challenged twice by OVA at 50 mg/mL for 1 week. The results showed that oral supplementation of L. plantarum A56 could effectively relieve allergic symptoms of mice, and decreased OVA-specific IgE and IgG1 concentrations. It also declined interleukin (IL)-4 level, raised interferon-γ (IFN-γ) in serum, and splenocyte supernatant, and the qPCR results were consistent with above results. Moreover, L. plantarum A56 treatment also fortified superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) levels, and reduced malondialdehyde (MDA) level in serum. The increased nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and forkhead box O1 (Foxo1) expression indicated that L. plantarum A56 exerted antioxidation through Nrf2-Foxo1 pathway. In addition, L. plantarum A56 treatment elevated Bacteroidetes richness, ASV/OTU number, species diversity, etc. Notably, Spearman correlation analysis indicated that Bacteroidetes displayed obviously negative correlation with IgE and IgG1, but Actinobacteria and Acidobacteria exhibited significantly positive correlation with IgG1 and IgE. Collectively, these results suggested that L. plantarum A56 could alleviate OVA-induced food allergy by regulating Th1/Th2 imbalance, antioxidation, and modulating intestinal microbiota.

Waxy maize starch incorporated (-)-epigallocatechin-3-gallate can stabilize emulsion gel and improve antioxidant activity.

A food-grade emulsion gel was stabilized using waxy maize starch (WS) incorporated (-)-epigallocatechin-3-gallate (EGCG) at different ratio (from 5 % to 20 %, w/w). The microstructure, rheological behavior, physical stability and antioxidant activity of emulsion gels were investigated using confocal laser scanning microscopy (CLSM), cryo-scanning electron microscopy (cryo-SEM), and rheometer, etc. The results suggested that incorporated EGCG obviously affected the spatial configuration of WS hydrogel. The WS/EGCG hydrogels presented an excellent lipophilic capacity characterized by tightly adhering to linseed oil droplets in the emulsion gels. Moreover, the viscosity, viscoelasticity and physical stability of the emulsion gels stabilized by the WS/EGCG hydrogel matrices were significantly enhanced. The emulsion gel stabilized by the WS/EGCG hydrogel matrix (15 % EGCG) had long-term emulsifying stability because its emulsified phase volume fraction (77.14 %) remained stable for 30 days. Compared with typical natural and synthetic antioxidants in food and pharmaceutical processing, the emulsion gels stabilized by the WS/EGCG hydrogel matrices showed significant stronger DPPH (97.45 %) and ABTS•+ (97.97 %) free radical scavenging activity. These results demonstrate that WS/EGCG hydrogels can not only be used in food-grade matrix materials to stabilize emulsion gels but also improve the antioxidant activity of the emulsion gels.

Preparation and bioactivity of the rare ginsenosides Rg3 and Rh2: An updated review.

Ginseng, an ancient medicinal herb, is used in oriental medicine for the treatment of various diseases. Saponins are the main bioactive components of ginseng, but the multiple glucosyl side chains on its molecules prevent ginsenosides from entering the blood through the intestinal membrane, thus reducing the efficacy. The preparation of rare ginsenosides, which are easy to be absorbed by human body and have higher drug activity, has been widely practiced by removing the sugar group of natural ginsenosides in vitro. Rare ginsenosides Rg3 and Rh2 have been approved as drugs or health supplements to improve immune function. This review summarizes the preparation methods of ginsenoside Rg3 and Rh2 in recent years. Ginsenoside Rg3 and Rh2 were prepared by biotransformation of protopanaxadiol type ginsenoside, with the highest conversion rate of 98.19% and 95.89% in the laboratory, respectively. At present, improving the conversion rate and reducing the production cost are still the bottleneck of industrial scale production of Rg3 and Rh2 through the deglycosylation directly from Rb1, Rb2, Rb3, Rc and Rd in the crude extract of ginseng. In addition, ginsenosides Rg3 and Rh2 play anti-inflammatory, anticancer, cardiovascular protective, immunomodulatory, neuroprotective, anti-diabetic, anti-fatigue, anti-allergic, anti-aging, antioxidant and other pharmacological effects by activating AMPK, JNK, NF-κB, MAPKs, P13K/AKT/mTOR and other signaling pathways. As potential drugs for prevention and treatment of various diseases, ginsenoside Rg3 and Rh2 need to further clarify other underlying mechanisms of action through in vitro and in vivo experiments.

Specific and efficient hydrolysis of all outer glucosyls in protopanaxadiol type and protopanaxatriol type ginsenosides by a ß-glucosidase from Thermoclostridium stercorarium.

To develop a new method for enzymatic preparation of minor ginsenosides, T. stercorarium ß-glucosidase (Tsbgl) was characterized and its activities of deglycosylation towards natural ginsenosides were examined. The substrates of 1 mmol l-1 were incubated with the enzyme of 38.3 U ml-1 at 65 â„ƒ and pH 5.0. The Km values of Tsbgl for ginsenosides Rb1, Rg1 and pNPG were 0.37 ± 0.03, 3.26 ± 0.19, and 1.24 ± 0.03 mmol l-1, and the Vmax values were 183.63 ± 7.15, 85.03 ± 4.90, and 117.66 ± 1.96 µmol mg-1 min-1, respectively. The molar conversion of ginsenosides Rb1, Rb2, Rb3, Rc, Re, Rg1, and Rf by Tsbgl within 6 h was 100%, 50.1%, 42.7%, 92.0%, 57.3%, 67.9%, and 76.8%, respectively. The yield of aglycone protopanaxadiol was 35.5 µmol l-1 h-1 for Rb1, while the yields of aglycone protopanaxatriol were 64.2 and 70.4 µmol l-1 h-1 for Rg1 and Rf. Tsbgl with good organic solvent tolerance, mild reaction conditions and broad substrate specificity, could completely remove all outer glucosyls at the C-3 and C-20 hydroxyls of protopanaxadiol-type ginsenosides, and the C-6 and C-20 hydroxyls of protopanaxatriol-type ginsenosides through various pathways, providing a specific and efficient way to produce minor ginsenosides.

Oral administration of Lactobacillus plantarum JC7 alleviates OVA-induced murine food allergy through immunoregulation and restoring disordered intestinal microbiota.

PURPOSE: The incidence and prevalence of food allergy have sharply risen over the past several decades. Oral administration of probiotic stains has been proven as a safe and effective method to control food allergy. In this study, it aims to comprehensively investigate the anti-allergic effect of Lactobacillus plantarum JC7. METHODS: Balb/c mice were randomly divided into three groups and received OVA (20 µg/mouse, intraperitoneal injection), L. plantarum JC7 (2 × 108 CFU/mouse, intragastric administration) + OVA (20 µg/mouse, intraperitoneal injection) or 0.9% saline (intragastric administration) for 3 weeks. Body weight was monitored weekly, and allergic reactions were evaluated after challenge of OVA. Serum levels of OVA-specific immunoglobulins and various cytokines were tested using ELISA, and the cecum microbiota was analysed by 16S rRNA sequencing to explore the relationships between these indicators and OVA-induced food allergy. Western blotting was used to identify the expression levels of phosphorylated IκBα and nuclear factor kappa B p65. RESULTS: OVA-sensitised mice showed mitigation of respiratory manifestations, alleviation of lung inflammation and congestion, and the presence of an intact intestinal villus structure. Furthermore, OVA-specific immunoglobulin E (IgE), OVA-specific-IgG1, and plasma histamine levels were declined in mice treated with L. plantarum JC7 than in OVA-sensitised mice. In addition, interferon-γ (IFN-γ) and interleukin 10 (IL-10) levels were significantly increased, while IL-4 and IL-17A levels were clearly decreased in mice that had undergone oral administration of L. plantarum JC7, compared with OVA-sensitised mice. These findings indicated imbalances of T helper cell type 1 (Th1)/Th2 and regulatory T cells (Treg)/Th17, which were confirmed by quantitative polymerase chain reaction (PCR). Western blotting demonstrated that the expression levels of phosphorylated IκBα and nuclear factor kappa B p65 were significantly increased in OVA-sensitised mice, but these changes were partly reversed after treatment with L. plantarum JC7. Oral administration of L. plantarum JC7 increased the richness, diversity, and evenness of cecum microbiota, characterised by higher Bacteroidetes abundance and lower Firmicutes abundance. Additionally, the intestinal microbial community composition was significantly altered in the OVA-sensitised group, indicating a disordered intestinal microbiota that was restored by the oral administration of L. plantarum JC7. CONCLUSION: Overall, L. plantarum JC7 can prevent food allergy by rectifying Th1/Th2 and Treg/Th17 imbalances, combined with modifications of disordered intestinal microbiota.

Metabolic differences in women with premature ovarian insufficiency: a systematic review and meta-analysis.

OBJECTIVE: This review aimed to investigate the metabolic profile of women with premature ovarian insufficiency (POI) compared relative to women with normal ovarian functioning. METHODS: A systematic search of PubMed, EMBASE, and the Web of Science for observational studies published up until the 6th of July 2021 that compared the metabolic profile of POI women with a healthy control group were assessed. Mean differences (MD) and 95% confidence interval (CI) were pooled using the fixed or random effect models. RESULTS: A total of 21 studies involving 1573 women with POI and 1762 control women were included. POI patients presented significantly higher waist circumference, total cholesterol, low-density lipoprotein, high-density lipoprotein, triglycerides, and fasting glucose. Additionally, POI patients had marginally higher insulin level. However, the differences in systolic, and diastolic blood pressure were non-significant relative to the control group. CONCLUSIONS: POI is associated with alterations in certain metabolic parameters compared to control women. This finding highlights the importance of early screening and the lifelong management of metabolic health for women with POI.

HB-EGF induces mitochondrial dysfunction via estrogen hypersecretion in granulosa cells dependent on cAMP-PKA-JNK/ERK-Ca2+-FOXO1 pathway.

Polycystic ovarian syndrome (PCOS) is one of the most prevalent endocrinopathies and the leading cause of anovulatory infertility, but its pathogenesis remains elusive. Although HB-EGF is involved in ovarian cancer progression, there is still no clarity about its relevance with PCOS. The present study exhibited that abundant HB-EGF was noted in follicular fluid from PCOS women, where it might induce the granulosa cells (GCs) production of more estrogen via the elevation of CYP19A1 expression after binding to EGFR. Furthermore, HB-EGF transduced intracellular downstream cAMP-PKA signaling to promote the phosphorylation of JNK and ERK whose blockage impeded the induction of HB-EGF on estrogen secretion. Meanwhile, HB-EGF enhanced the accumulation of intracellular Ca2+ whose chelation by BAPTA-AM abrogated the stimulation of HB-EGF on FOXO1 along with an obvious diminishment for estrogen production. cAMP-PKA-JNK/ERK-Ca2+ pathway played an important role in the crosstalk between HB-EGF and FOXO1. Treatment of GCs with HB-EGF resulted in mitochondrial dysfunction as evinced by the reduction of ATP content, mtDNA copy number and mitochondrial membrane potential. Additionally, HB-EGF facilitated the opening of mitochondrial permeability transition pore via targeting BAX and raised the release of cytochrome C from mitochondria into the cytosol to trigger the apoptosis of GCs, but this effectiveness was counteracted by estrogen receptor antagonist. Collectively, HB-EGF might induce mitochondrial dysfunction and GCs apoptosis through advancing estrogen hypersecretion dependent on cAMP-PKA-JNK/ERK-Ca2+-FOXO1 pathway and act as a promising therapeutic target for PCOS.

MiR-let-7d-3p inhibits granulosa cell proliferation by targeting TLR4 in polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is a typical reproductive and endocrinological disorder of women at child-bearing age. In this study, we used miRNA sequencing technology and verified miR-let-7d-3p as a vital miRNA in PCOS. RT-qPCR confirmed miR-let-7d-3p was significantly increased in granulosa cells (GCs) of PCOS. Cell counting kit-8 (CCK-8) identified the suppression of miR-let-7d-3p mimic in KGN cell proliferation and PI3K/Akt signaling pathway. Dual luciferase reporter assay proved that Toll-like receptor 4 (TLR4) was a target of miR-let-7d-3p, and TLR4 was significantly down-regulated by miR-let-7d-3p. Furthermore, over-expression of TLR4 promoted KGN cell proliferation and rescued the inhibition of miR-let-7d-3p on KGN cells. In conclusion, miR-let-7d-3p was a crucial miRNA up-regulated in GCs of PCOS, and inhibited cell proliferation by targeting TLR4 gene.

Predictive value of circulating sex hormone-binding globulin for gestational diabetes: a meta-analysis.

Aim: To detect predictive value of preconception or early pregnancy sex hormone-binding globulin (SHBG) for subsequent gestational diabetes mellitus (GDM). Materials & methods: We searched Embase, Medline, PubMed, Web of Science and Cochrane library up to January 2020. Studies assessing diagnostic performance of SHBG for GDM diagnosed by well-defined diagnostic criteria using oral glucose tolerance test. Results: Totally seven studies with 1947 women were included and 247 were diagnosed as GDM. SHBG had a combined diagnostic odds ratio of 6.68 (95% CI: 4.58-9.74), sensitivity of 0.70 (95% CI: 0.51-0.84), specificity of 0.74 (95% CI: 0.52-0.88), positive likelihood ratio of 2.49 (95% CI: 1.73-3.57) and negative likelihood ratio of 0.37 (95% CI: 0.23-0.61). The area under the summary receiver operating characteristic curve was 0.78 (95% CI: 0.74-0.82). Conclusion: SHBG had a predictive value for GDM and might improve GDM screening. However, heterogeneity between studies warrants more research into this topic.

Predictive value of the number of frozen blastocysts in live birth rates of the transferred fresh embryos.

BACKGROUND: Blastocyst development by extended culture in vitro allows the embryos to 'select' themselves, thus successful growth to the blastocyst stage is a reflection of the developmental competence of cleavage stage embryos in a cohort. The study aims to determine whether the number of frozen blastocysts is associated with live birth rates of the transferred fresh embryos. METHOD: The retrospective study included 8676 cycles of first fresh embryo transfer from January 2016 to June 2019 at a fertility center of a university hospital. The patients with ≥ 10 oocytes retrieved were divided into three groups according to the number of frozen blastocysts: 0 (group 1), 1-2 (group 2), and ≥ 3 (group 3). The primary outcome measure was the live birth. The secondary outcome measures included clinical pregnancy rates and implantation rates. Logistic regression analysis was also performed. RESULTS: Live birth rates in patients with ≥ 3 and 1-2 frozen blastocysts were 47.6% and 46.1%, respectively, which were significantly higher than that in patients without blastocyst (36.0%). The clinical pregnancy rate in group 3 was 65.1%, which was also significantly higher than the other two groups (47.0% and 59.2%). The implantation rates were 35.5%, 47.6%, and 56.0% in the three groups, respectively (P < 0.001). Compared with groups of frozen blastocysts, 0 frozen blastocyst yielded a lower rate of live birth (the adjusted odds ratio: 0.526, 95% CI: 0.469, 0.612). CONCLUSION: In patients with optimal ovarian response that retrieved ≥ 10 oocytes, fresh embryos transfer followed by having blastocysts frozen is a strong indicator of pregnancy achievement, but the number of frozen blastocysts (if not = 0) has limited value in predicting live birth rates.

Correlative research of the incidence of preeclampsia and sperm exposure.

PURPOSE: This study aimed to evaluate the incidence of preeclampsia after a long duration or a short duration of sperm exposure with the biological father. METHODS: Analyze the clinical and follow-up data of 502 single birth primigravid women in Women's Hospital, School of Medicine, Zhejiang University. They were divided into two groups according to the duration of sperm exposure with the biological father, short duration of sperm exposure (≤ 3 months) and long duration of sperm exposure (≥ 12 months). Basic information and clinical characteristics in each group were evaluated. RESULTS: A total of 502 patients were followed, included 122 long duration of sperm exposure and 380 short duration of sperm exposure. Patients in the long duration group were younger than the short group (aged 31.49 ± 3.21 vs 27.49 ± 3.21 years, P < 0.001). These two groups had no statistical significant in patient's body mass index, education level, gestational age, birth weight, fetal birth weight, fetal sex and delivery mode (P > 0.05). Stratified analysis with the cutoff of 30 year-old suggested that the incidence of pregnancy-induced hypertension (PIH)/preeclampsia (PE) of short duration group was significantly higher than the long duration group (OR 2.82; 95% CI 1.08-7.41), so as PE (OR 10.28; 95% CI 1.01-105.02). Stratified analysis suggested no significantly increased or decreased risk for PIH (OR 1.59; 95% CI 0.54-4.68), gestational diabetes mellitus (OR 0.6; 95% CI 0.31-1.18), intrahepatic cholestasis of pregnancy (OR 2.49; 95% CI 0.34-18.48) or fetal anomaly (OR 0.4; 95% CI 0.14-1.20). CONCLUSION: A long duration of sperm exposure with the biological father may reduce the incidence of PE.

Comparison of allergenicity among cow, goat, and horse milks using a murine model of atopy.

Due to the prevalence and severity of cow milk (CM) allergy (CMA), an ideal substitute is urgently needed to develop hypoallergenic infant formula for infants who experience anaphylaxis to typical whey-based CM formula. Goat milk (GM) and horse milk (HM) are considered appropriate substitutes; however, whether GM and HM are less allergenic than CM is unclear. In the present study, the difference in allergenicity among CM, GM, and HM was investigated using the Balb/c mouse model. The number of mice with severe respiratory symptoms was significantly lower in the GM- and HM-sensitised groups than in the CM-sensitised group. Furthermore, histologic examination of intestinal and lung tissues revealed a thinner lamina propria of the small intestine and obvious inflammation and congestion in lungs in the CM-sensitised group than in the GM- and HM-sensitised groups. CM-specific immunoglobulin (Ig) E, serum IgG1, and plasma histamine levels were also higher in CM-sensitised mice than in GM- or HM-sensitised mice. In addition, higher interleukin (IL) 4 and IL-17A levels and lower interferon-γ (IFN-γ) and IL-10 levels were observed in CM-sensitised mice compared with GM- and HM-sensitised mice, according to qPCR, indicating Th1/Th2 and Treg/Th17 imbalances. The CM-sensitised group had a higher proportion of IL-4- and IL-17A-producing CD3+ T cells but a lower proportion of IFN-γ- and IL-10-producing CD3+ T cells compared with the GM- and HM-sensitised groups, confirming the Th1/Th2 and Treg/Th17 imbalances. In conclusion, GM and HM were less allergenic than CM in mice as a result of a shift in the Th1/Th2 and Treg/Th17 imbalances; however, HM was less allergenic than GM and can be used as an alternative milk to develop infant formulas for children with CMA.

Effects of Different Exposure Days to Gonadotropin-Releasing Hormone Agonist (GnRH-a) on Live Birth Rates in the Depot GnRH-a Protocol: A Retrospective Analysis of 7007 Cycles.

BACKGROUND In controlled ovarian hyperstimulation protocols worldwide, depot gonadotropin-releasing hormone agonist (GnRH-a) pretreatment is generally used for pituitary desensitization. The delay between the GnRH-a administration and starting gonadotropin treatment varies greatly, from 25 to 60 days. However, the association between exposure days to GnRH-a before the onset of gonadotropin administration and the clinical outcomes remains unknown. MATERIAL AND METHODS This retrospective study included 7007 patients who underwent fresh embryo transfers between February 2016 and July 2019. The duration of pituitary downregulation was categorized into 3 groups: group 1, ≤30 days; group 2, 31-35 days; and group 3, ≥36 days. The rates of live birth were compared as the main outcome measure. Logistic regression analysis was also performed after controlling for a range of confounders. RESULTS The number of patients in groups 1, 2, and 3 was 2001, 2824, and 2182, respectively. Group 3 (≥36 days) had a noticeably higher live birth rate (48.1%) than the other 2 groups (42.6% and 43.9%, P=0.001). The rate of live birth was remarkably enhanced in group 3 (adjusted odds ratio: 1.264, 95% confidence interval: 1.098, 1.455, P=0.001) after controlling for confounders, while the difference was not found in group 2 (P=0.512) compared with group 1. CONCLUSIONS In the depot GnRH-a protocol, live birth rates are higher among patients needing a longer time to achieve the goal of pituitary downregulation.

Risk Factors for Stillbirth among Pregnant Women Infected with Syphilis in the Zhejiang Province of China, 2010-2016.

BACKGROUND: The World Health Organization estimated that about 1.36 million pregnant women suffered from syphilis in 2008, and nearly 66% of adverse effects occurred in those who were not tested or treated. Syphilis infection is one of the most common maternal factors associated with stillbirth. OBJECTIVE: This study aimed to determine the risk factors for stillbirth among pregnant women infected with syphilis. METHODS: In this retrospective study, data on stillbirth and gestational syphilis from 2010 to 2016 were extracted from the prevention of mother-to-child transmission (PMTCT) program database in the Zhejiang province. A total of 8,724 pregnant women infected with syphilis were included. Multiple logistic regression analysis was performed to determine the degree of association between gestational syphilis and stillbirth. RESULTS: We found that the stillbirth percentage among pregnant women infected with syphilis was 1.7% (152/8,724). Compared with live births, stillbirth was significantly associated with lower maternal age, not being married, lower gravidity, the history of syphilis, nonlatent syphilis stage, higher maternal serum titer for syphilis, inadequate treatment for syphilis, and later first antenatal care visit. In multiple logistic analysis, nonlatent syphilis (adjusted odds ratio (AOR) = 2.03; 95% CI = 1.17, 3.53) and maternal titers over 1 : 4 (AOR = 1.78; 95% CI = 1.25, 2.53) were risk factors for stillbirth, and adequate treatment was the only protective factor for stillbirth (AOR = 0.16; 95% CI = 0.10, 0.25). CONCLUSIONS: Nonlatent syphilis and maternal titers over 1 : 4 were risk factors for stillbirth, and adequate treatment was the only protective factor for stillbirth.

Effect of Hyperinsulinemia and Insulin Resistance on Endocrine, Metabolic, and Reproductive Outcomes in Non-PCOS Women Undergoing Assisted Reproduction: A Retrospective Cohort Study.

Objective: To evaluate the effect of hyperinsulinemia (HI) and insulin resistance (IR) on endocrine, metabolic, and reproductive outcomes in women without polycystic ovary syndrome (PCOS) undergoing assisted reproduction. Materials and Methods: The study included 1,104 non-PCOS women undergoing in vitro fertilization/intracytoplasmic sperm injection-fresh embryo transfer. HI was evaluated by serum fasting insulin (FIN), and IR was evaluated by homeostatic model assessment of insulin resistance index (HOMA-IR). In addition, biometric, sex hormone, and metabolic parameters were measured. Independent t-test, linear, and logistic regression examined associations between HI, IR, and endocrine, metabolic, ovarian stimulation characteristics, and reproductive outcomes. Results: Women with HI and IR had lower levels of progesterone, luteinizing hormone, follicle-stimulating hormone, estradiol, high-density lipoproteins, and increased levels of triglycerides low-density lipoproteins. For ovarian stimulation characteristics, those with HI and IR had a longer duration of stimulation, a higher total gonadotropin dose, and a lower peak estradiol level. Linear regression confirmed these associations. For reproductive outcomes, HI and IR were not associated with clinical pregnancy, live birth, and miscarriage. Conclusions: HI and IR did not impair reproductive outcomes in non-PCOS women undergoing assisted reproduction.

Comparison of GnRH-a Prolonged Protocol and Short GnRH-a Long Protocol in Patients with Thin Endometrium for Assisted Reproduction: A Retrospective Cohort Study.

PURPOSE: Gonadotrophin releasing hormone agonist (GnRH-a) is widely used for pituitary down-regulation and recruiting more follicles in assisted reproduction. However, no information is available on its value for patients with thin endometrial thickness. PATIENTS AND METHODS: This was a retrospective cohort study of 302 patients with endometrium <8 mm undergoing fresh embryo transfer at a fertility center of a university hospital from January 2016 and December 2018. In 148 cycles of the GnRH-a prolonged protocol, one depot of 3.75 mg GnRH-a was injected on day 2 of the menstrual cycle, while in 154 cycles of the short GnRH-a long protocol, 0.1 mg of GnRH-a was injected daily from the mid-luteal phase. The live birth rate and clinical pregnancy rate were compared between the two groups. Other outcome measures included the implantation rate, miscarriage rate, and characteristics of stimulation procedures. RESULTS: Live birth rates and clinical pregnancy rates were significantly higher in the GnRH-a prolonged protocol group than in the other group (36.5% vs 20.8%, P=0.002; 43.9% vs 28.2%, P=0.006, respectively). The live birth rate was significantly increased in the prolonged protocol group (crude OR: 2.190, 95% CI: 1.311, 3.660; adjusted OR: 2.458, 95% CI: 1.430, 4.224) compared with that in the reference group. The implantation rate of the former group was also significantly higher than that of the latter group (35.4% vs 15.9%, P=0.000). There was no significant difference in miscarriage rates between the two protocols. In terms of stimulation procedures, the GnRH-a prolonged protocol group required significantly higher Gn time (10.9 vs 9.5 days, P=0.000) and Gn consumption (2625.0 vs 2047.5 IU, P=0.000) than the short GnRH-a long protocol group. CONCLUSION: The GnRH-a prolonged protocol in fresh embryo transfer cycles yielded better clinical outcomes of patients with thin endometrium than the short GnRH-a long protocol.

Antidepressant-like effects of Lactobacillus plantarum DP189 in a corticosterone-induced rat model of chronic stress.

Probiotic antidepressant effects demonstrated previously in clinical studies and animal models act via unknown mechanisms. Here we used a corticosterone injection-induced Sprague-Dawley rat chronic stress exposure model to investigate antidepressant-like effects of potential probiotic Lactobacillus plantarum DP189 (DP189) isolated from Chinese traditional fermented sauerkraut. After administration of DP189 (1.0 × 109CFU/d) suspension by gavage for 21 days, behavioral, histopathological and biochemical changes were assessed, including hippocampal neuronal apoptosis assessments via TUNEL staining and Western blot analysis. Behaviorally, DP189 treatment improved memory and spatial learning and reduced anhedonia, as measured using Morris water maze and sucrose preference tests, respectively. Histopathologically, DP189 treatment ameliorated hippocampal pathological changes and dramatically reduced TUNEL-positive cell numbers. Biochemically, DP189 decreased serum IL-1ß and TNF-α levels, decreased hippocampal mitogen-activated protein kinase kinase 7 and c-Jun N-terminal kinase 2 levels, down-regulated pro-apoptosis protein Bax immunocontent and up-regulated anti-apoptosis protein Bcl-2 immunocontent. Collectively, these results suggest that DP189 treatment may prevent and/or alleviate depression-like behaviors and hippocampal neural injury induced by CORT.

Lactobacillus plantarum NA136 ameliorates nonalcoholic fatty liver disease by modulating gut microbiota, improving intestinal barrier integrity, and attenuating inflammation.

Gut microbiota dysbiosis, associated with insulin resistance, weak intestinal barrier integrity, and inflammation, may also play a role in the development of dietary-induced nonalcoholic fatty liver disease (NAFLD). This study investigates the effects of dietary Lactobacillus plantarum NA136 administration on gut microbiota composition in an insulin-resistant C57BL/6J mouse NAFLD model. Comparison of mice with and without L. plantarum NA136 treatment revealed that L. plantarum NA136 treatment not only relieved insulin resistance but also significantly increased relative proportions of Desulfovibrio, Alistipes, Prevotella, and Enterorhabdus in gut microbiota of NAFLD mice. Meanwhile, L. plantarum NA136 administration also inhibited pathogenic bacterial growth, while promoting growth of probiotics such as Allobaculum, Lactobacillus, and, most markedly, Bifidobacterium. Moreover, L. plantarum NA136 treatment of NAFLD mice improved intestinal barrier integrity and attenuated high-fat and fructose diet (HFD/F)-induced inflammation. These results implicate gut-liver-axis-dependent microbiota modulation as the underlying mechanism for L. plantarum NA136-induced amelioration of NAFLD.Key points• L. plantarum NA136 corrects gut microbiota disorders caused by a high-fat and fructose diet. • L. plantarum NA136 strengthens the intestinal barrier and reduces inflammation in the liver. • L. plantarum NA136 relieves NAFLD by improving the gut-liver axis.

Malic enzyme 1 is important for uterine decidualization in response to progesterone/cAMP/PKA/HB-EGF pathway.

Malic enzyme 1 (Me1), a member of the malic enzymes involving in glycolytic pathway and citric acid cycle, is essential for the energy metabolism and maintenance of intracellular redox balance state, but its physiological role and regulatory mechanism in the uterine decidualization are still unknown. Current study showed that Me1 was strongly expressed in decidual cells, and could promote the proliferation and differentiation of stromal cells followed by an accelerated cell cycle transition, indicating an importance of Me1 in the uterine decidualization. Silencing of Me1 attenuated NADPH generation and reduced GR activity, while addition of NADPH improved the defect of GR activity elicited by Me1 depletion. Further analysis found that Me1 modulated intracellular GSH content via GR. Meanwhile, Me1 played a role in maintaining mitochondrial function as indicated by these observations that blockadge of Me1 led to the accumulation of mitochondrial O2- level and decreased ATP production and mtDNA copy numbers accompanied with defective mitochondrial membrane potential. In uterine stromal cells, progesterone induced Me1 expression through PR-cAMP-PKA pathway. Knockdown of HB-EGF might impede the regulation of progesterone and cAMP on Me1. Collectively, Me1 is essential for uterine decidualization in response to progesterone/cAMP/PKA/HB-EGF pathway and plays an important role in preventing mitochondrial dysfunction.