Structural and pharmacological insights into cordycepin for neoplasms and metabolic disorders.

Cytotoxic adenosine analogues were among the earliest chemotherapeutic agents utilised in cancer treatment. Cordycepin, a natural derivative of adenosine discovered in the fungus Ophiocordyceps sinensis, directly inhibits tumours not only by impeding biosynthesis, inducing apoptosis or autophagy, regulating the cell cycle, and curtailing tumour invasion and metastasis but also modulates the immune response within the tumour microenvironment. Furthermore, extensive research highlights cordycepin's significant therapeutic potential in alleviating hyperlipidaemia and regulating glucose metabolism. This review comprehensively analyses the structure-activity relationship of cordycepin and its analogues, outlines its pharmacokinetic properties, and strategies to enhance its bioavailability. Delving into the molecular biology, it explores the pharmacological mechanisms of cordycepin in tumour suppression and metabolic disorder treatment, thereby underscoring its immense potential in drug development within these domains and laying the groundwork for innovative treatment strategies.

Amnioinfusion compared with expectant management in oligohydramnios with intact amnions in the second and early third trimesters.

INTRODUCTION: Treatment of oligohydramnios in the mid-trimester is challenging, because of the high incidence of adverse perinatal outcomes mainly due to bronchopulmonary dysplasia. Antenatal amnioinfusion has been proposed as a possible treatment for oligohydramnios with intact amnions, but there are few relevant studies. This study aimed to evaluate the effectiveness of transabdominal amnioinfusion in the management of oligohydramnios without fetal lethal malformations in the second and early third trimesters. MATERIAL AND METHODS: It is a historical cohort study. A total of 79 patients diagnosed with oligohydramnios at 18-32 weeks gestation were enrolled. In the amnioinfusion group (n = 39), patients received transabdominal amnioinfusion with the assistance of real-time ultrasound guidance. In the expectant group (n = 41), patients were treated with 3000 mL of intravenous isotonic fluids daily. The perioperative complications and perinatal outcomes were analyzed. RESULTS: Compared with the expectant group, the delivery latency was significantly prolonged, and the rate of cesarean delivery was significantly reduced in the amnioinfusion group (p < 0.05). Although the rate of intrauterine fetal death was significantly reduced, the incidence of spontaneous miscarriage, premature rupture of membranes (PROMs), and threatened preterm labor were significantly higher in the amnioinfusion group than in the expectant group (p < 0.05). There was no significant difference in terms of perinatal mortality (28.9% vs. 41.4%, p > 0.05). Multivariate logistic regression revealed that amnioinfusion (odds ratio [OR] 0.162, 95% confidence interval [CI] 0.04-0.61, p = 0.008) and gestational age at diagnosis (OR 0.185, 95% CI 0.04-0.73, p = 0.016) were independently associated with neonatal adverse outcomes. Further subgrouping showed that amnioinfusion significantly reduced the frequency of bronchopulmonary hypoplasia for patients ≤26 weeks (26.7% vs. 75.0%, p = 0.021). The rates of other neonatal complications were similar in both groups. CONCLUSIONS: Amnioinfusion has no significant effect on improving the perinatal mortality of oligohydramnios in the second and early third trimesters. It may lead to a relatively high rate of PROM and spontaneous abortion. However, amnioinfusion may significantly improve the latency period, the rate of cesarean delivery, and neonatal outcomes of oligohydramnios, especially for women ≤26 weeks with high risk of neonatal bronchopulmonary hypoplasia.

Higher vitamin B6 dietary consumption is associated with a lower risk of glaucoma among United States adults.

Objective: Although numerous studies have substantiated the neuroprotective effects of vitamin B6 on the optic nerve and its enhancement of visual function, comprehensive data delineating the correlation between vitamin B6 and glaucoma at a national demographic scale remain insufficient. This study is designed to explore the link between the dietary consumption of vitamin B6 and glaucoma. Methods: This study included 3,850 individuals aged 40 and older from the National Health and Nutrition Examination Survey (NHANES), spanning 2005-2008. Dietary consumption of vitamin B6 was calculated from the average of two 24-h dietary recall interviews. Glaucoma was diagnosed in accordance with the established Rotterdam criteria. To evaluate the relationship between vitamin B6 dietary consumption and the risk of glaucoma, we employed Restricted Cubic Splines and weighted multivariable logistic regression analysis. We employed stratified and three other sensitivity analyses to confirm the robustness of our results, and conducted a preliminary exploration of the potential association between vitamin B6 supplement consumption and glaucoma risk. Results: After adjusting for covariates, we found a significant inverse correlation between dietary consumption of vitamin B6 and glaucoma risk (p non-linearity = 0.18; p for trend = 0.02). Stratified analysis and three other sensitivity analyses revealed stability in the outcomes (all p for interaction>0.05). Compared to the lowest quartile of consumption (≤1.23 mg/day), individuals in the highest quartile of vitamin B6 consumption (>2.34 mg/day) experienced a 75% reduction in glaucoma risk (OR = 0.25, 95% CI 0.07-0.92). However, the effect of vitamin B6 supplements on glaucoma was inconclusive. Conclusion: A diet high in vitamin B6 inversely correlates with glaucoma risk, suggesting that increasing dietary intake of vitamin B6 could be a viable preventative strategy against glaucoma among adults in the United States.

Circular RNA differential expression profiles and bioinformatics analysis of hsa_circRNA_079422 in human endometrial carcinoma.

The aim of our study was to explore circular RNA (circRNA) expression profiles associated with human endometrial carcinoma (EC) and to analyse the molecular mechanisms involved in cancer development and their potential clinical importance. Differential expression profiles were revealed by Arraystar human circRNA microarray analysis. The results of the circRNA microarray were confirmed by quantitative real-time PCR. Interactions between circRNAs and microRNAs (miRNAs) were predicted using Arraystar's miRNA target prediction software. The functions of the circRNA-miRNA coexpression network were identified by KEGG pathway analysis and GO analysis. Compared with para-tumorous tissues, 14 genes were significantly upregulated and 12 genes were significantly downregulated in EC tissues (P < 0.05). The quantitative real-time PCR data demonstrated consistency with the results of the microarray profile analysis. We generated a circRNA-miRNA coexpression network. Hsa_circRNA_079422 expression was significantly lower and miR-136-5p expression was higher in EC tissues than in normal endometrial tissues. KEGG pathway analysis and GO analysis indicated that hsa_circRNA_079422 might play roles in different signalling pathways and biological functions. We confirmed the presence of different circRNA expression profiles and predicted the circRNA-miRNA coexpression network in human EC tissues. Hsa_circRNA_079422 might be involved in the pathogenesis and biological process of EC via interactions with miRNAs.IMPACT STATEMENTWhat is already known on this subject? EC is a common malignancy of the female reproductive system. CircRNAs were demonstrated to exert critical roles in cancers, including EC.What do the results of this study add? The results of this study add circRNAs expression profiles, the circRNA-miRNA coexpression network and cancer-related circRNA-miRNA target genes in EC. It was first found that hsa_circRNA_079422 was downregulated, while miR-136-5p was upregulated in EC tissues.What are the implications of these findings for clinical practice and/or further research? In clinical practice, early EC diagnosis lacks specific biomarkers, so most EC patients are diagnosed at an advanced stage. In the management of EC patients, we also lack personalised adjuvant treatment that combines the clinical pathological characteristics. For the existing literature, we identified a new EC differential expression biomarker, hsa_circ_079422. It can be used to verify the correlation with EC clinical severity or poor prognosis. Its targeting can also be used to stratify EC patients with different molecular types, including to guide adjuvant therapy. In addition, we can verify and analyse regulatory pathways associated with it for the design of regulating engineering circRNA.

The role of internal iliac artery intraoperative vascular clamp temporary occlusion in abnormally invasive placenta.

OBJECTIVE: To investigate the efficacy of internal iliac artery intraoperative vascular clamp temporary occlusion in the treatment of abnormally invasive placenta. METHOD: This retrospective study enrolled 153 patients diagnosed with abnormally invasive placenta between January 2018 and December 2021. The patients were divided into a study group (n = 88, undergoing cesarean section followed by internal iliac artery vascular clamp temporary occlusion) and a control group (n = 65, receiving routine cesarean section). The general situation, intraoperative conditions, postoperative complications, and neonatal outcomes were compared between the two groups. RESULTS: The hysterectomy rate in the study group was significantly lower than that in the control group. However, there were no significant differences in intraoperative blood loss, blood transfusion, postoperative intensive care unit transfer rate, or neonatal outcome between the groups. Further subgrouping showed that in patients with placenta increta, the hysterectomy rate and intraoperative bleeding amount were significantly lower in the occlusion group. Nevertheless, these advantages were not significantly different between the groups in patients with placenta percreta. CONCLUSION: Vascular clamp temporary occlusion of internal iliac artery is an effective method for controlling hemorrhage and decreasing the incidence of hysterectomy in patients with placenta increta. For patients with placenta percreta, the benefit is limited.

Uteroplacental-Cerebral Ratio: A Doppler Parameter for Prognostic Prediction of Late-Onset Fetal Growth Restriction: Single Center Prospective Cohort Study.

Purpose: This study aimed to elucidate the accuracy of Doppler parameters in predicting the prognosis of late-onset fetal growth restriction (FGR). Methods: This was a prospective study of 114 pregnancies. Doppler parameters, including the cerebroplacental ratio and pulsatility index (PI) in the middle cerebral, umbilical, uterine artery, were recorded. The new uteroplacental−cerebro ratio (UPCR) was constructed as the ratio of (umbilical artery + mean of the left and right uterine artery) to middle cerebral artery PI. Logistic regression analyses and receiver operating characteristic curves were performed. Results: Adverse outcomes occurred in 37 (32%) neonates. The z values of the middle cerebral artery PI and cerebroplacental ratio were lower (p < 0.001), while the z values of the umbilical artery PI, mean uterine artery PI, and UPCR (p < 0.001) were higher in late-onset FGR in those with compared to those without adverse outcomes. Multivariate logistic regression revealed that only UPCR was independently associated with adverse outcomes (p < 0.001). For predicting the prognosis of late-onset FGR, UPCR showed a fair degree of accuracy (area under the curve [AUC], 0.824). Conclusion: The new UPCR, reflecting the impact of placental impedance from both fetal and maternal sides on fetal well-being, improves the accuracy of prognostic prediction for late-onset FGR.

Characterization of Diaporthe species associated with peach constriction canker, with two novel species from China.

Species of Diaporthe infect a wide range of plants and live in vivo as endophytes, saprobes or pathogens. However, those in peach plants are poorly characterized. In this study, 52 Diaporthe strains were isolated from peach branches with buds, showing constriction canker symptoms. Phylogenetic analyses were conducted using five gene regions: internal transcribed spacer of the ribosomal DNA (ITS), translation elongation factor 1-α (TEF), ß-tubulin (TUB), histone (HIS), and calmodulin (CAL). These results coupled with morphology revealed seven species of Diaporthe, including five known species (D. caryae, D. cercidis, D. eres, D. hongkongensis, and D. unshiuensis). In addition, two novel species D. jinxiu and D. zaofenghuang are introduced. Except for the previously reported D. eres, this study represents the first characterization of Diaporthe species associated with peach constriction canker in China, and contributes useful data for practicable disease management.

The protective effects of human umbilical cord mesenchymal stem cell-derived extracellular vesicles on cisplatin-damaged granulosa cells.

OBJECTIVE: Long term exposure to gonadotoxic chemotherapy is becoming a major cause of premature ovarian failure/insufficiency (POF/POI) with the increasing cancer incidence among young women. The present study was designed to investigate the protective effects of human cord mesenchymal stem cells (HUCMSCs)-derived extracellular vesicles (EVs) on cisplatin (CDDP)-damaged granulosa cells (GCs) in vitro. MATERIALS AND METHODS: EVs were obtained from supernatant of cultured HUCMSCs by ultracentrifugation method, purified by Sucrose density gradient centrifugation, and then were co-cultured with cisplatin-damaged GCs of 3-weeks female Sprague-Dawley (SD) rats. PKH26 labeled EVs could be observed in normal and CDDP-damaged GCs after 6 h co-culture. RESULTS: The surviving GCs were significantly higher and apoptotic GCs were significantly lower in EVs + CDDP group compared with CDDP group. Meanwhile, the levels of E2 and StAR (the key gene related to synthesis of steroid hormone) were significantly higher in EVs + CDDP group compared with CDDP group. Furthermore, the mRNA expression of Caspase 3 was down-regulated significantly and the ratio of Bcl-2/Bax was up-regulated significantly in EVs + CDDP group. Moreover, the protective effect of EVs on CDDP-damaged GCs showed a dose-dependent effect. CONCLUSION: HUCMSCs-derived EVs could become incorporated to CDDP-damaged GCs, and increase the number of living cells, therefore playing important roles in promoting resistance to cisplatin-induced GCs apoptosis and restoring synthesis and secretion of steroid hormone in GCs. This study might provide a theoretical and experimental basis for use of mesenchymal stem cells (MSCs) derived EVs instead of MSCs as a cell-free therapeutic strategy for the patients with POI induced by chemotherapeutic agents.

[Phylogenetic structure of Abies georgei var. smithii community at different spatial scales in Sygera Mountains of Tibet, China]. / 不同空间尺度西藏色季拉山急尖长苞冷杉群落谱系结构特征.

We analyzed the phylogenetic structure of trees within six diameter classes (1-2, 2-4, 4-7, 7-11, 11-16, >16 cm) in quadrats with different size of 5 m×5 m,10 m×10 m, 20 m×20 m, 50 m×50 m, 100 m×100 m in a Abies georgei var. smithii community in a 4 hm2 stem-mapping plot located in subalpine dark coniferous forest of Sygera Mountains, southeast Tibet. In various spatial scales, both net relatedness index (NRI) and nearest taxon index (NTI) of the community were larger than zero, indicating a clustered phylogenetic structure with the largest clustering intensity at small spatial scale (5 m×5 m). Community of small-size classes were phylogenetically clustering. In large-size classes (DBH>7 cm) phylogenetic over dispersion became more common, with dispersion increased with increasing tree size under all spatial scales. The intensity of phylogenetic clustering in young trees increased with increasing spatial scales, while the intensity of over dispersion in large trees (DBH>7 cm) increased with spatial scale. Our results suggested that environmental filtering in small-size trees and competitive exclusion in large-size trees might be the main ecological processes driving community assembly in this region.

Extracellular Vesicles Derived from Mesenchymal Stem Cells Recover Fertility of Premature Ovarian Insufficiency Mice and the Effects on their Offspring.

It has been reported that extracellular vesicles (EVs) derived from human umbilical cord mesenchymal stem cells (HUCMSCs) can promote the proliferative and secretive functions of granulosa cells. In vivo study further demonstrated that EVs derived from HUCMSCs can not only promote the angiogenesis of ovarian tissue but also restore the function of an ovary of chemically induced premature ovarian insufficiency (POI) mice. However, no study investigates the effects of HUCMSCs derived EVs on fertility recovery of POI mice and evaluating their offspring. This study investigates the effects of HUCMSCs derived EVs on fertility recovery and the cognitive function of their offspring. A POI model was established by intraperitoneal injection of cyclophosphamide (CTX) and busulfan (BUS), and randomly divided into EVs-transplantation group (a single injection of 150 µg EVs proteins which suspended in 0.1 ml phosphate buffer saline [PBS] via tail vein), POI group (a single injection of 0.1 ml PBS via tail vein), and normal control group (a single injection of 0.1 ml PBS via tail vein without intraperitoneal injection of CTX and BUS). After EVs treatment, not only the ovarian function of POI mice recovered but also the fertility increased with less time to get pregnant, evaluating by in vitro fertilization and mating test. Cognitive behaviors of the offspring were similar among the three groups through the Y-maze test and novel object recognition task. An anti-apoptotic effect was identified through immunohistochemistry, real-time polymerase chain reaction and western blot. These findings indicate that HUCMSCs derived EVs can improve the fertility of POI mice without adverse effects on the cognitive behavior of their offspring, highlighting the potential value of EVs to be a cell-free therapy for patients suffering from POI.

Therapeutic effects of human umbilical cord mesenchymal stem cell-derived microvesicles on premature ovarian insufficiency in mice.

BACKGROUND: Premature ovarian insufficiency (POI) is one of the leading causes of female infertility, which is caused by an abnormal ovarian reserve. Currently, there is no effective treatment to restore the fertility of POI patients. Recent studies suggested that microvesicles (MVs) released from mesenchymal stem cells (MSCs) exert therapeutic effects in various degenerative diseases. In this study, the effect of human umbilical cord MSC-derived MVs (HUCMSC-MVs) on the restoration of ovarian function in a chemotherapy-induced POI mouse model is investigated. METHODS: MVs were obtained from the supernatant of cultured HUCMSCs. The localization of PKH26-labeled HUCMSC-MVs in ovarian tissues was observed by confocal laser scanning microscopy. Histomorphometric analysis was performed to count the number of ovarian follicles and vessels. The ovarian sections were stained with anti-CD34 to evaluate angiogenesis. The levels of estradiol (E2) and follicle-stimulating hormone (FSH) were measured by enzyme-linked immunosorbent serologic assay. The mRNA expression of angiogenesis-related cytokines and the protein expression of AKT in mouse ovaries were measured by quantitative RT-PCR and western blot analysis. The parametric variables were compared by Student's t test and analysis of variance. The non-parametric variables were compared by the Mann-Whitney U test. Categorical variables were compared by χ2 test. P < 0.05 was considered statistically significant. RESULTS: PKH26-labeled HUCMSC-MVs were detectable within the ovaries and migrated to the ovarian follicles 24 h after transplantation. The transplantation of HUCMSC-MVs could increase the body weight and number of ovarian follicles (primordial, developing, and preovulatory follicles), induce ovarian angiogenesis, and recover the disturbed estrous cycle of POI mice. The expression levels of total AKT, p-AKT, and angiogenic cytokines (including VEGF, IGF, and angiogenin) in the ovaries of POI mice were markedly upregulated after HUCMSC-MVs transplantation, suggesting that HUCMSC-MVs transplantation might recover ovarian function by inducing angiogenesis via the PI3K/AKT signaling pathway. CONCLUSIONS: This study provides valuable insight into the effects of HUCMSC-MVs on ovarian tissue angiogenesis and on the restoration of ovarian function in POI mice, which may be helpful to develop a treatment strategy for POI patients.