Comparison of pregnancy outcomes in women with normal ovarian response to the gonadotropin-releasing hormone agonist protocol using different trigger methods: a single-center retrospective cohort study based on propensity score matching.

PURPOSE: To investigate whether gonadotropin-releasing hormone agonist (GnRH-a) combined with human chorionic gonadotropin (HCG) can improve pregnancy outcomes in patients with normal ovarian response (NOR). METHODS: In this retrospective cohort study, data of 404 NOR patients undergoing fresh embryo transfer (ET) from 2018 to 2022 were studied. Patients were divided into HCG group and HCG plus GnRH-a group according to trigger methods. After confounding factors were controlled by propensity score matching, 67 cases were included in HCG group and HCG plus GnRH-a group, respectively, and pregnancy outcomes were assessed. Basal data, ovarian stimulation, embryological data and pregnancy outcomes were compared. The effect of trigger methods on pregnancy outcomes was analyzed by binary logistic regression. RESULTS: There was no statistically significant differences in embryological data, embryo implantation rate, clinical pregnancy rate, live birth rate of ET, number of fresh embryos transferred and total number of embryos transferred after one cycle of oocyte retrieval. While, cumulative live birth rate (CLBR) was better in the dual-trigger group than in the HCG group. The binary logistic regression analysis indicated that the trigger methods had an independent influence on embryo implantation and cumulative live birth. CONCLUSIONS: During IVF/ICSI, dual-trigger could potentially play a role in improving oocyte quality, ensuring embryo implantation rate, clinical pregnancy rate, live birth rate of ET and cumulative live birth rate at the end of one ovum pick-up (OPU) cycle, and reducing the physical, temporal and financial negative consequences due to repeated OPU cycle.

Corrigendum to "Cilengitide inhibits osteoclast adhesion through blocking the αvß3-mediated FAK/Src signaling pathway" [Heliyon 9(7) (July 2023) e17841].

[This corrects the article DOI: 10.1016/j.heliyon.2023.e17841.].

Is there any difference in urinary continence between bilateral and unilateral nerve sparing during radical prostatectomy? A systematic review and meta-analysis.

CONTEXT: In men with prostate cancer, urinary incontinence is one of the most common long-term side effects of radical prostatectomy (RP). The recovery of urinary continence in patients is positively influenced by preserving the integrity of the neurovascular bundles (NVBs). However, it is still unclear if bilateral nerve sparing (BNS) is superior to unilateral nerve sparing (UNS) in terms of post-RP urinary continence. The aim of this study is to systematically compare the differences in post-RP urinary continence outcomes between BNS and UNS. METHODS: The electronic databases of PubMed and Web of Science were comprehensively searched. The search period was up to May 31, 2023. English language articles comparing urinary continence outcomes of patients undergoing BNS and UNS radical prostatectomy were included. Meta-analyses were performed to calculate pooled relative risk (RR) estimates with 95% confidence intervals for urinary continence in BNS and UNS groups at selected follow-up intervals using a random-effects model. Sensitivity analyses were performed in prospective studies and robotic-assisted RP studies. RESULTS: A meta-analysis was conducted using data from 26,961 participants in fifty-seven studies. A meta-analysis demonstrated that BNS improved the urinary continence rate compared to UNS at all selected follow-up points. RRs were 1.36 (1.14-1.63; p = 0.0007) at ≤ 1.5 months (mo), 1.28 (1.08-1.51; p = 0.005) at 3-4 mo, 1.12 (1.03-1.22; p = 0.01) at 6 mo, 1.08 (1.05-1.12; p < 0.00001) at 12 mo, and 1.07 (1.00-1.13; p = 0.03) at ≥ 24 mo, respectively. With the extension of the follow-up time, RRs decreased from 1.36 to 1.07, showing a gradual downward trend. Pooled estimates were largely heterogeneous. Similar findings were obtained through sensitivity analyses of prospective studies and robotic-assisted RP studies. CONCLUSION: The findings of this meta-analysis demonstrate that BNS yields superior outcomes in terms of urinary continence compared to UNS, with these advantages being sustained for a minimum duration of 24 months. It may be due to the real effect of saving the nerves involved. Future high-quality studies are needed to confirm these findings.

Causal association between rheumatoid arthritis and pregnancy loss and intrauterine growth retardation: A bidirectional two-sample Mendelian randomization study.

OBJECTIVE: To investigate the causal relationship between rheumatoid arthritis (RA) and pregnancy loss and intrauterine growth retardation (IUGR) using Mendelian randomization (MR). METHODS: Genetic variants associated with RA (12,555 cases and 240,862 controls), miscarriage (1475 cases and 149,622 controls), and IUGR (3558 cases and 207,312 controls) were obtained from the FinnGen consortium, and supplementary data on RA (5201 cases and 457,732 controls) and miscarriage (7069 cases and 250,492 controls) were obtained from the Medical Research Council Integrated Epidemiology Unit (MRC-IEU). 47 Single nucleotide polymorphisms (SNPs) associated with RA were screened as instrumental variables (IV). The causal relationship between RA and pregnancy loss and IUGR were assessed by 5 MR methods, mainly inverse variance weighting (IVW). Sensitivity analyses were also performed to test the stability of the results. RESULTS: Bidirectional MR showed that genetically predicted RA was causally associated with pregnancy loss and IUGR in forward MR analyses, and that RA significantly increased pregnancy loss [odds ratio (OR) = 1.13, 95% confidence interval (CI): 1.00-1.33, P = .03] and IUGR (OR = 1.08, 95% CI: 1.01-1.15, P = .019). In the reverse MR, there was no causal association between pregnancy loss (P = .15) and IUGR (P = .87) and RA. CONCLUSION: This study found a significant genetic association between RA and pregnancy loss and IUGR. RA is considered to be a high-risk factor for adverse maternal outcomes. Pre-pregnancy prophylaxis and intra-pregnancy control of patients should be emphasized to reduce the incidence of adverse pregnancy outcomes such as pregnancy loss and IUGR.

UGT89AC1-mediated quercetin glucosylation is induced upon herbivore damage and enhances Camellia sinensis resistance to insect feeding.

Quercetin is a key flavonol in tea plants (Camellia sinensis (L.) O. Kuntze) with various health benefits, and it often occurs in the form of glucosides. The roles of quercetin and its glucosylated forms in plant defense are generally not well-studied, and remain unknown in the defense of tea. Here, we found higher contents of quercetin glucosides and a decline of the aglucone upon Ectropis grisescens (E. grisescens) infestation of tea. Nine UGTs were strongly induced, among which UGT89AC1 exhibited the highest activity toward quercetin in vitro and in vivo. The mass of E. grisescens larvae that fed on plants with repressed UGT89AC1 or varieties with lower levels of UGT89AC1 was significantly lower than that of larvae fed on controls. Artificial diet supplemented with quercetin glucoside also reduced the larval growth rate, whereas artificial diet supplemented with free quercetin had no significant effect on larval growth. UGT89AC1 was located in both the cytoplasm and nucleus, and its expression was modulated by JA, JA-ILE, and MeJA. These findings demonstrate that quercetin glucosylation serves a defensive role in tea against herbivory. Our results also provide novel insights into the ecological relevance of flavonoid glycosides under biotic stress in plants.

Distribution of and Temporal Variation in Volatiles in Tea (Camellia sinensis) Flowers during the Opening Stages.

Tea (Camellia sinensis) flowers emit a large amount of volatiles that attract pollinators. However, few studies have characterized temporal and spatial variation in tea floral volatiles. To investigate the distribution of volatiles within tea flowers and their variation among opening stages, volatile components from different parts of tea flowers and different opening stages were collected by headspace solid-phase microextraction and analyzed by gas chromatography-mass spectrometry. A total of 51 volatile compounds of eight chemical classes were identified in the tea flowers. Volatile compounds were most abundant in tea flowers of the Shuchazao cultivar. Acetophenone, 1-phenylethanol, 2-phenylethanol, and benzyl alcohol were the most abundant volatiles. Terpenes were common in the sepals, and benzoids were common in the stamens. The fatty acid derivatives were mainly distributed in the pistils and receptacles and were less abundant in the petals, sepals, and stamens. During the opening phase of tea flowers, the volatile content increased 12-fold, which mainly stemmed from the increase in benzoids. These results enhance our understanding of the formation of volatiles in tea flowers.

LH level on the antagonist administration day as a predictor of the reproductive outcomes in women with normal ovarian function.

Introduction: The addition of antagonists is mainly based on estrogen level and follicle size, while LH level has not received sufficient attention.In this study, LH Level on the antagonist administration day was used as the main research objective to explore its relationship with laboratory indicators and pregnancy outcomes. Methods and Analysis: We enrolled 854 patients with normal ovarian function undergoing in-vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) between May 2021 to May 2022 at the Reproductive Center of Shandong University of Traditional Chinese Medicine.We used the quartile method to group LH levels on the antagonist administration day. There were four groups: Q1 (0.53IU/L≤LH ≤ 1.89IU/L); Q2 (1.89IU/L

Afzelin protects against doxorubicin-induced cardiotoxicity by promoting the AMPKα/SIRT1 signaling pathway.

BACKGROUND: Doxorubicin (DOX), a chemotherapeutic drug, could relieve the progressions of various diseases. However, its clinical application is limited due to its cardiotoxicity. This study aimed to investigate the effects of afzelin (a flavonol glycoside found in Houttuynia cordata) on the cardiotoxicity induced by DOX. METHODS: In ex-vivo, H9C2 cells were incubated with 20, 40, or 80 µM afzelin for 12 h, followed by the treatment with 1 µM DOX for 12 h. In vivo, C57BL/6 J mice were intraperitoneally injected with 4 mg/kg/day DOX on days 1, 7, and 14. Meanwhile, starting from day 1, mice were intragastrically administrated with 5 mg/kg/day or 10 mg/kg/day afzelin for 20 days. The cardiac function of mice was evaluated by detecting hemodynamic parameters using the M-mode echocardiography. RESULTS: DOX decreased the cell survival rate, and elevated apoptotic rate, as well as induced the oxidative stress and mitochondrial dysfunction in H9C2 cells. All these changes were alleviated by afzelin treatment in a concentration-dependent manner. The results were further proven by the mitigation of cardiac injury in vivo, as evidenced by the elevation of fractional shortening, heart weight/tibia length, and the rate of the increase/decrease of left ventricular pressure in mice subjected to DOX-induced cardiotoxicity. Furthermore, afzelin upregulated the expression of p-AMP-activated protein kinase alpha (AMPKα) and sirtuin1 (SIRT1). Dorsomorphin (an AMPKα inhibitor) abrogated the anti-cardiotoxicity effects of afzelin in H9C2 cells induced by DOX. CONCLUSION: Afzelin protected against DOX-induced cardiotoxicity by promoting the AMPKα/SIRT1 signaling pathway.

Causal association between psycho-psychological factors, such as stress, anxiety, depression, and irritable bowel syndrome: Mendelian randomization.

BACKGROUND: Pathogenesis, diagnosis, and treatment of irritable bowel syndrome (IBS) have been reported to be challenging hotspots in clinical practice. Previous observational studies have found that stress, anxiety, depression, and other mental and psychological diseases are closely associated with IBS. This study aimed to further explore the causal relationships of these associations through Mendelian randomization (MR). METHODS: The data needed for MR were obtained from publicly published genome-wide association databases. We performed a bidirectional, 2-sample MR analysis using instrumental variables (IV) associated with stress, anxiety, and depression, and other mental and psychological factors as exposures and IBS as the outcome. A reverse MR analysis with IBS as exposure and stress, anxiety, depression, and other mental and psychological factors as the outcomes was also performed. The inverse variance weighting (IVW) method was adopted as the main method of MR, and the causal effect between stress, anxiety, depression, and other mental and psychological factors and IBS was evaluated as the main result of the study. In addition, a series of sensitivity analyses was conducted to comprehensively evaluate the causal relationship between them. RESULTS: Stress, anxiety, depression, and other mental and psychological factors were the underlying etiologies for IBS (odds ratio [OR] = 1.06, 95% confidence interval [CI]: 1.03-1.08), and they were positively correlated. Univariate analysis further supported the above conclusions (Depression, [OR = 1.31, 95% CI: 1.05-1.63, P = .016], Anxiety, [OR = 1.53, 95% CI: 1.16-2.03, P = .003]). However, in reverse MR analysis, we found that IBS did not affect stress, anxiety, depression, or other mental and psychological factors and that there was no causal relationship between IBS and stress, anxiety, depression, or other mental and psychological factors (P > .05). CONCLUSION: This study demonstrates that mental and psychological factors are the underlying etiologies for IBS. These findings may provide important information for physicians regarding the clinical treatment of IBS.

Volatile compound-mediated plant-plant interactions under stress with the tea plant as a model.

Plants respond to environmental stimuli via the release of volatile organic compounds (VOCs), and neighboring plants constantly monitor and respond to these VOCs with great sensitivity and discrimination. This sensing can trigger increased plant fitness and reduce future plant damage through the priming of their own defenses. The defense mechanism in neighboring plants can either be induced by activation of the regulatory or transcriptional machinery, or it can be delayed by the absorption and storage of VOCs for the generation of an appropriate response later. Despite much research, many key questions remain on the role of VOCs in interplant communication and plant fitness. Here we review recent research on the VOCs induced by biotic (i.e. insects and pathogens) and abiotic (i.e. cold, drought, and salt) stresses, and elucidate the biosynthesis of stress-induced VOCs in tea plants. Our focus is on the role of stress-induced VOCs in complex ecological environments. Particularly, the roles of VOCs under abiotic stress are highlighted. Finally, we discuss pertinent questions and future research directions for advancing our understanding of plant interactions via VOCs.

Citric acid-modified pH-sensitive bone-targeted delivery of estrogen for the treatment of postmenopausal osteoporosis.

Bone targeted delivery of estrogen offers great promise for the clinical application of estrogen in the treatment of postmenopausal osteoporosis (PMOP). However, the current bone-targeted drug delivery system still has several issues that need to be solved, such as the side effects of bone-targeted modifier molecules and the failure of the delivery system to release rapidly in the bone tissue. It is important to aggressively search for new bone-targeted modifier molecules and bone microenvironment-responsive delivery vehicles. Inspired by the distribution of citric acid (CA) mainly in bone tissue and the acidic bone resorption microenvironment, we constructed a CA-modified diblock copolymer poly(2-ethyl-2-oxazoline)-poly(ε-caprolactone) (CA-PEOz) drug delivery system. In our study, we found that the CA modification significantly increased the bone targeting of this drug delivery system, and the delivery system was able to achieve rapid drug release under bone acidic conditions. The delivery system significantly reduced bone loss in postmenopausal osteoporotic mice with a significant reduction in estrogenic side effects on the uterus. In summary, our study shows that CA can act as an effective bone targeting modifier molecule and provides a new option for bone targeting modifications. Our study also provides a new approach for bone-targeted delivery of estrogen for the treatment of PMOP.

Cilengitide inhibits osteoclast adhesion through blocking the αvß3-mediated FAK/Src signaling pathway.

The remodeling of actin cytoskeleton of osteoclasts on the bone matrix is essential for osteoclastic resorption activity. A specific regulator of the osteoclast cytoskeleton, integrin αvß3, is known to provide a key role in the degradation of mineralized bone matrixes. Cilengitide is a potent inhibitor of integrins and is capable of affecting αvß3 receptors, and has anti-tumor and anti-angiogenic and apoptosis-inducing effects. However, its function on osteoclasts is not fully understood. Here, the cilengitide role on nuclear factor κB ligand-receptor activator (RANKL)-induced osteoclasts was explored. Cells were cultured with varying concentrations of cilengitide (0,0.002,0.2 and 20 µM) for 7 days, followed by detected via Cell Counting Kit-8, staining for tartrate resistant acid phosphatase (TRAP), F-actin ring formation, bone resorption assays, adhesion assays, immunoblotting assays, and real-time fluorescent quantitative PCR. Results demonstrated that cilengitide effectively restrained the functionality and formation of osteoclasts in a concentration-dependent manner, without causing any cytotoxic effects. Mechanistically, cilengitide inhibited osteoclast-relevant genes expression; meanwhile, cilengitide downregulated the expression of key signaling molecules associated with the osteoclast cytoskeleton, including focal adhesion kinase (FAK), integrin αvß3 and c-Src. Therefore, this results have confirmed that cilengitide regulates osteoclast activity by blocking the integrin αvß3 signal pathway resulting in diminished adhesion and bone resorption of osteoclasts.

Physiological functions of podosomes: From structure and function to therapy implications in osteoclast biology of bone resorption.

With increasing age, bone tissue undergoes significant alterations in composition, architecture, and metabolic functions, probably causing senile osteoporosis. Osteoporosis possess the vast majority of bone disease and associates with a reduction in bone mass and increased fracture risk. Bone loss is on account of the disorder in osteoblast-induced bone formation and osteoclast-induced bone resorption. As a unique bone resorptive cell type, mature bone-resorbing osteoclasts exhibit dynamic actin-based cytoskeletal structures called podosomes that participate in cell-matrix adhesions specialized in the degradation of mineralized bone matrix. Podosomes share many of the same molecular constitutions as focal adhesions, but they have a unique structural organization, with a central core abundant in F-actin and encircled by scaffolding proteins, kinases and integrins. Here, we conclude recent advancements in our knowledge of the architecture and the functions of podosomes. We also discuss the regulatory pathways in osteoclast podosomes, providing a reference for future research on the podosomes of osteoclasts and considering podosomes as a therapeutic target for inhibiting bone resorption.

Evaluation of the Efficacy of Enterococcus faecium L3 as a Feed Probiotic Additive in Chicken.

The study was devoted to the comparison of the probiotic effect of enterococcal Enterococcus faecium L3 to the antibiotic enramycin as a chicken feed additive. Two hundred and sixteen chickens were divided into three groups and tested by different parameters including weight gain, food consumption, blood biochemistry, immunology, and caecal microbiome at two checkpoints, 21 and 39 days after birth. By the end of the experiment, a group of chickens getting probiotic demonstrated weight gain of more than 100 g at the average relative to the control group with no additive in animal feed (P < 0.05). Blood serum biochemistry showed a significant increase in HDL level (P < 0.05) relative to the control group. The 16S RNA sequencing demonstrated the growth abundance of Lachnospiraceae and the decrease of Proteobacteria in probiotic fed group. On the contrary, the antibiotic fed group showed a noticeable increase in the abundance of Proteobacteria which included the genus Salmonella. Thus, probiotic E. faecium L3 being added to chicken food as a single additive may be considered as a possible replacement of antibiotic enramycin.

LEP and LEPR are possibly a double-edged sword for wound healing.

Wound healing is a complex and error-prone process. Wound healing in adults often leads to the formation of scars, a type of fibrotic tissue that lacks skin appendages. Hypertrophic scars and keloids can also form when the wound-healing process goes wrong. Leptin (Lep) and leptin receptors (LepRs) have recently been shown to affect multiple stages of wound healing. This effect, however, is paradoxical for scarless wound healing. On the one hand, Lep exerts pro-inflammatory and profibrotic effects; on the other hand, Lep can regulate hair follicle growth. This paper summarises the role of Lep and LepRs on cells in different stages of wound healing, briefly introduces the process of wound healing and Lep and LepRs, and examines the possibility of promoting scarless wound healing through spatiotemporal, systemic, and local regulation of Lep levels and the binding of Lep and LepRs.

Circadian clock genes as promising therapeutic targets for bone loss.

The circadian clock regulates many key physiological processes such as the sleep-wake cycle, hormone release, cardiovascular health, glucose metabolism and body temperature. Recent evidence has suggested a critical role of the circadian system in controlling bone metabolism. Here we review the connection between bone metabolism and the biological clock, and the roles of these mechanisms in bone loss. We also analyze the regulatory effects of clock-related genes on signaling pathways and transcription factors in osteoblasts and osteoclasts. Additionally, osteocytes and endothelial cells (ECs) regulated by the circadian clock are also discussed in our review. Furthermore, we also summarize the regulation of circadian clock genes by some novel modulators, which provides us with a new insight into a potential strategy to prevent and treat bone diseases such as osteoporosis by targeting circadian genes.

Up-regulation of miR-133a-3p promotes ovary insulin resistance on granulosa cells of obese PCOS patients via inhibiting PI3K/AKT signaling.

BACKGROUND: MicroRNAs are a type of non-coding single-stranded RNA, which is involved in the regulation of ovary insulin resistance (IR). This study aims to explore the underlying mechanisms of miR-133a-3p regulating ovary IR in obese polycystic ovary syndrome (PCOS). METHODS: Granulosa cells (GCs) were extracted from follicular fluids of PCOS patients (obese PCOS group and non-obese PCOS group) and healthy women (control group). The expression of miR-133a-3p in GCs was detected by qRT-PCR. The targets and pathways of miR-133a-3p were predicted by bioinformatics analyses. The protein levels of PI3K, p-AKT, GLUT4, p-GSK-3ß, and p-FOXO1 were measured by Western blotting. RESULTS: MiR-133a-3p was highly expressed in GCs from PCOS patients, especially in obese PCOS patients. The protein levels of PI3K and p-AKT was downregulated in GCs from PCOS patients. There were 11 target genes of miR-133a-3p enriching in PI3K/AKT signaling pathway. miR-133a-3p mimic downregulated the expression of PI3K, p-AKT, and GLUT4, and upregulated the protein levels of p-GSK-3ß and p-FOXO1. miR-133a-3p inhibitor presented the opposite effect of miR-133a-3p mimic. CONCLUSION: MiR-133a-3p promotes ovary IR on GCs of obese PCOS patients via inhibiting PI3K/AKT signaling pathway. This study lays a foundation for further research on the mechanism of ovary IR in obese PCOS patients.

The ASIC3-M-CSF-M2 macrophage-positive feedback loop modulates fibroblast-to-myofibroblast differentiation in skin fibrosis pathogenesis.

Inflammation is one of the main pathological features leading to skin fibrosis and a key factor leading to the progression of skin fibrosis. Acidosis caused by a decrease in extracellular pH is a sign of the inflammatory process. Acid-sensing ion channels (ASICs) are ligand-gated ion channels on the cell membrane that sense the drop in extracellular pH. The molecular mechanisms by which skin fibroblasts are regulated by acid-sensing ion channel 3 (ASIC3) remain unknown. This study investigated whether ASIC3 is related to inflammation and skin fibrosis and explored the underlying mechanisms. We demonstrate that macrophage colony-stimulating factor (M-CSF) is a direct target of ASIC3, and ASIC3 activation promotes M-CSF transcriptional regulation of macrophages for M2 polarization. The polarization of M2 macrophages transduced by the ASIC3-M-CSF signal promotes the differentiation of fibroblasts into myofibroblasts through transforming growth factor ß1 (TGF-ß1), thereby producing an ASIC3-M-CSF-TGF-ß1 positive feedback loop. Targeting ASIC3 may be a new treatment strategy for skin fibrosis.

Insight into the role of DPP-4 in fibrotic wound healing.

Wound healing is a complex and long-term process consisting of hemostasis, inflammation, proliferation, and maturation/remodeling. These four stages overlap and influence each other; they affect wound healing in different ways, and if they do not function perfectly, they may cause scarring, proliferative scarring and keloid formation. A therapeutic target affecting wound healing in multiple ways will help the healing process proceed more effectively. DPP-4/CD26 is a multifunctional dimorphic glycoprotein widely distributed on the surface of a variety of cells, including fibroblasts and keratin-forming cells. It has been found to affect periwound inflammation, re-epithelialization, extracellular matrix secretion and skin fibrosis and is a potential target for promoting wound healing and inhibiting scar formation. After presenting a brief introduction of the wound healing process and DPP-4/CD26, this paper summarizes the effects of DPP-4/CD26 on cells involved in different stages of wound healing and discusses the feasibility of DPP-4/CD26 as a multifunctional target for the treatment of wound healing and inhibition of scar formation.