Unsuccessful laparoscopic resection of a large pelvic solitary fibrous tumor: A case report.

We present a rare case of a female pelvic solitary fibrous tumor unsuccessfully resected using single-port laparoscopy, requiring conversion to laparotomy. Although the resection was successful, the surgical approach could have been improved. For large tumors, minimally invasive results are possible with flexible choices of equipment and incision position.

Disturbing cytoskeleton by engineered nanomaterials for enhanced cancer therapeutics.

Cytoskeleton plays a significant role in the shape change, migration, movement, adhesion, cytokinesis, and phagocytosis of tumor cells. In clinical practice, some anti-cancer drugs achieve cytoskeletal therapeutic effects by acting on different cytoskeletal protein components. However, in the absence of cell-specific targeting, unnecessary cytoskeletal recombination in organisms would be disastrous, which would also bring about severe side effects during anticancer process. Nanomedicine have been proven to be superior to some small molecule drugs in cancer treatment due to better stability and targeting, and lower side effects. Therefore, this review summarized the recent developments of various nanomaterials disturbing cytoskeleton for enhanced cancer therapeutics, including carbon, noble metals, metal oxides, black phosphorus, calcium, silicon, polymers, peptides, and metal-organic frameworks, etc. A comprehensive analysis of the characteristics of cytoskeleton therapy as well as the future prospects and challenges towards clinical application were also discussed. We aim to drive on this emerging topic through refreshing perspectives based on our own work and what we have also learnt from others. This review will help researchers quickly understand relevant cytoskeletal therapeutic information to further advance the development of cancer nanomedicine.

A Polyoxometalate-Encapsulated Metal-Organic Framework Nanoplatform for Synergistic Photothermal-Chemotherapy and Anti-Inflammation of Ovarian Cancer.

Photothermal therapy (PTT), as a noninvasive and local treatment, has emerged as a promising anti-tumor strategy with minimal damage to normal tissue under spatiotemporally controllable irradiation. However, the necrosis of cancer cells during PTT will induce an inflammatory reaction, which may motivate tumor regeneration and resistance to therapy. In this study, polyoxometalates and a chloroquine diphosphate (CQ) co-loaded metal-organic framework nanoplatform with hyaluronic acid coating was constructed for efficient ovarian cancer therapy and anti-inflammation. Our results demonstrated that this nanoplatform not only displayed considerable photothermal therapeutic capacity under 808 nm near-infrared laser, but also had an impressive anti-inflammatory capacity by scavenging reactive oxygen species in the tumor microenvironment. CQ with pH dependence was used for the deacidification of lysosomes and the inhibition of autophagy, cutting off a self-protection pathway induced by cell necrosis-autophagy, and achieving the synergistic treatment of tumors. Therefore, we combined the excellent properties of these materials to synthesize a nanoplatform and explored its therapeutic effects in various aspects. This work provides a promising novel prospect for PTT/anti-inflammation/anti-autophagy combinations for efficient ovarian cancer treatment through the fine tuning of material design.

Transcriptomic analysis supports collective endometrial cell migration in the pathogenesis of adenomyosis.

RESEARCH QUESTION: Adenomyosis is a common uterine disorder of uncertain causes. Can transcriptomic analyses of the endometrium and myometrium reveal potential mechanisms underlying adenomyosis pathogenesis? DESIGN: Transcriptomic profiles of eutopic endometrium and myometrium from women with and without diffuse adenomyosis and with symptomatic FIGO type 2-5 fibroids in the proliferative phase of the menstrual cycle were assessed using RNA sequencing and bioinformatic analysis. Differentially expressed genes (DEG) and potential pathways were validated by quantitative reverse transcription polymerase chain reaction, immunoblotting and Masson staining, using additional clinical samples. RESULTS: Top biological processes in the endometrium of women with versus without adenomyosis, enriched from DEG, comprised inflammation, extracellular matrix (ECM) organization, collagen degradation and hyaluronan synthesis, which are key in cell migration and cell movement. Top biological processes enriched from DEG in the myometrium of women with versus without adenomyosis revealed ECM organization dysfunction, abnormal sensory pain perception and gamma aminobutyric acid (GABA) synaptic transmission. Dysregulation of prolactin signalling was also enriched in eutopic endometrium and in the myometrium of women with adenomyosis. CONCLUSIONS: Overall, our results support the invasive endometrium theory in the pathogenesis of adenomyosis, in which inflammation induces ECM remodelling resulting in a track for subsequent endometrial collective cell migration and onset of adenomyosis. Moreover, abnormal myometrial GABA synaptic transmission may contribute to dysmenorrhoea in women with adenomyosis and is a possible target for novel therapeutic development. Prolactin signalling abnormalities may serve as another opportunity for therapeutic intervention.

Enhanced postoperative cancer therapy by iron-based hydrogels.

Surgical resection is a widely used method for the treatment of solid tumor cancers. However, the inhibition of tumor recurrence and metastasis are the main challenges of postoperative tumor therapy. Traditional intravenous or oral administration have poor chemotherapeutics bioavailability and undesirable systemic toxicity. Polymeric hydrogels with a three-dimensional network structure enable on-site delivery and controlled release of therapeutic drugs with reduced systemic toxicity and have been widely developed for postoperative adjuvant tumor therapy. Among them, because of the simple synthesis, good biocompatibility, biodegradability, injectability, and multifunctionality, iron-based hydrogels have received extensive attention. This review has summarized the general synthesis methods and construction principles of iron-based hydrogels, highlighted the latest progress of iron-based hydrogels in postoperative tumor therapy, including chemotherapy, photothermal therapy, photodynamic therapy, chemo-dynamic therapy, and magnetothermal-chemical combined therapy, etc. In addition, the challenges towards clinical application of iron-based hydrogels have also been discussed. This review is expected to show researchers broad perspectives of novel postoperative tumor therapy strategy and provide new ideas in the design and application of novel iron-based hydrogels to advance this sub field in cancer nanomedicine.

A near-infrared triggered upconversion/MoS2 nanoplatform for tumour-targeted chemo-photodynamic combination therapy.

The combination of photodynamic therapy and chemotherapy has shown a great potential in cancer treatment. As a promising photosensitizer, MoS2 quantum dots (QDs) have limited application due to the low tissue penetration of its light absorbing wavelength in the ultraviolet and visible regions. For the purpose of utilizing MoS2QDs in higher NIR absorption region, herein, we constructed a core/shell nano-photosensitizer upconversion@MoS2 with doxorubicin loading. This nanoplatform can convert 980 nm NIR into visible light, activating MoS2QDs to produce reactive oxygen species through fluorescence resonance energy transfer. In addition, this nanoplatform presented good biocompatibility and tumor targeting after polyethylene glycol and folic acid modification. Interestingly, with pH-responsive drug release performance, this nanoplatform presented efficient chemotherapy effects. Thus, the tumour-targeted nanoplatform can achieve up-converted luminescence imaging guided chemo-photodynamic synergistic therapy effectively.

Biomimetic Nanomaterials Triggered Ferroptosis for Cancer Theranostics.

Ferroptosis, as a recently discovered non-apoptotic programmed cell death with an iron-dependent form, has attracted great attention in the field of cancer nanomedicine. However, many ferroptosis-related nano-inducers encountered unexpected limitations such as immune exposure, low circulation time, and ineffective tumor targeting. Biomimetic nanomaterials possess some unique physicochemical properties which can achieve immune escape and effective tumor targeting. Especially, certain components of biomimetic nanomaterials can further enhance ferroptosis. Therefore, this review will provide a comprehensive overview on recent developments of biomimetic nanomaterials in ferroptosis-related cancer nanomedicine. First, the definition and character of ferroptosis and its current applications associated with chemotherapy, radiotherapy, and immunotherapy for enhancing cancer theranostics were briefly discussed. Subsequently, the advantages and limitations of some representative biomimetic nanomedicines, including biomembranes, proteins, amino acids, polyunsaturated fatty acids, and biomineralization-based ferroptosis nano-inducers, were further spotlighted. This review would therefore help the spectrum of advanced and novice researchers who are interested in this area to quickly zoom in the essential information and glean some provoking ideas to advance this subfield in cancer nanomedicine.

Effect of HCG-Triggered Ovulation on Pregnancy Outcomes in Intrauterine Insemination: An Analysis of 5,610 First IUI Natural Cycles With Donor Sperm in China.

Objective: To evaluate the effect of human chorionic gonadotropin (hCG) trigger ovulation on pregnancy outcomes in natural IUI cycles with donor sperm. Methods: This retrospective cohort study included 5,610 first-natural IUI cycles with donor sperm in infertile couples during the period from January 2012 to December 2017. To control for other confounding factors, our analysis was restricted to normo-ovulatory women without tubal infertility. The main outcome measure was live birth rate; the secondary outcomes included rates of clinical pregnancy and miscarriage. Results: In the crude analysis, both the clinical pregnancy (27.40 vs. 22.73%; P = 0.001) and live birth rates (24.52 vs. 20.13%; P = 0.007) were significantly higher for the hCG group than for the spontaneous LH group. After adjustment for a number of confounding factors, the reproductive outcomes were still significantly worse for the spontaneous ovulatory group. Conclusions: Among women undergoing natural cycle IUI with donor sperm, hCG triggered ovulation for timing insemination offers beneficial impacts on both clinical pregnancy rates and live birth rates.

LRP6 regulates Rab7-mediated autophagy through the Wnt/ß-catenin pathway to modulate trophoblast cell migration and invasion.

Pre-eclampsia is a common complication during pregnancy; however, the underlying mechanisms of the crosstalk between low-density lipoprotein receptor-related protein 6 (LRP6) and autophagy in trophoblast cells are still not fully explored. Messenger RNA (mRNA) and protein levels of LRP6, beclin 1, Unc-51-like autophagy activating kinase 1 (ULK1), p62, vimentin, matrix metallopeptidase-9 (MMP-9), ß-catenin, c-Myc, and Rab7, as well as the ratio of LC3-II/LC3-I, were analysed by quantitative real-time polymerase chain reaction or Western blot analysis, respectively. An MTT assay was used to measure cell growth, and transwell and wound healing assays were carried out to evaluate the invasion and migration abilities of the trophoblasts used. An immunofluorescence assay was used to measure LC3. The mRFP-GFP-LC3 tandem fluorescence assay was applied to detect autophagic flow. LRP6 overexpression was achieved by constructing pcDNA3.1-LRP6 vectors. LRP6 was expressed at low levels in HTR-8/SVneo cells under hypoxia/reoxygenation (H/R) conditions. H/R inhibited the activation of autophagy. LRP6 overexpression promoted cell proliferation and activated autophagy, which led to the upregulation of beclin 1 and ULK1, as well as the ratio of LC3-II/LC3-I and the downregulation of p62. Furthermore, LRP6 overexpression elevated the migration and invasion abilities of the indicated cells and increased vimentin and MMP-9 expression levels. Furthermore, LRP6 upregulated Rab7 and activated autophagy through the Wnt/ß-catenin pathway. The late autophagy inhibitor bafilomycin A1 (Baf-A1) and the Wnt/ß-catenin pathway inhibitor PKF115-584 reversed the effects of LRP6 on trophoblast autophagy, migration and invasion. LRP6 promotes Rab7-mediated autophagy by activating the Wnt/ß-catenin pathway, which leads to increasing migration and invasion of trophoblast cells. Our study paves a new avenue for clinical treatment, and LRP6 may serve as an essential target in pre-eclampsia.

MiR-337-3p suppresses proliferation of epithelial ovarian cancer by targeting PIK3CA and PIK3CB.

Epithelial ovarian cancer (EOC) is responsible for nearly 140,000 deaths worldwide each year. MicroRNAs play critical roles in cancer development and progression. The function of microRNA miR-337-3p has been described in various cancers. However, the biological role of miR-337-3p and its molecular mechanisms underlying EOC initiation and progression have not been reported. Here, we reported that the expression of miR-337-3p is down-regulated in EOC tissues and low expression of miR-337-3p is correlated with advanced pathological grade for patients. Ectopic expression of miR-337-3p inhibited proliferation and induced apoptosis and cell cycle arrest in G0/G1 phase of EOC cells. PIK3CA and PIK3CB were revealed to be direct targets of miR-337-3p for reducing the activation of PI3K/AKT signaling pathway. PIK3CA and PIK3CB were discovered to affect cell proliferation of EOC cells in combination, and only when overexpressed simultaneously in miR-337-3p-expressing cells, could fully restore cell proliferation. In vivo investigation confirmed that miR-337-3p is a tumor suppressor that control expression of PIK3CA and PIK3CB encoded protein: p110α and p110ß. Altogether, our results demonstrate that miR-337-3p is a tumor suppressor in EOC that inhibits the expression of PIK3CA and PIK3CB.

Hsa-miRNA-125b may induce apoptosis of HTR8/SVneo cells by targeting MCL1.

MiR-125b regulates the kinds of cells that undergo apoptosis physiologically and pathologically. However, whether miR-125b affects the apoptotic behavior of trophoblasts and the underlying molecular regulatory mechanisms remains unclear. This study investigated the effect of miR-125b on apoptosis of HTR-8/SVneo cells in vitro. Constructed wild-type reporter vector (Wt-3'UTR) or mutated type reporter vector (Mut-3'UTR) reporter plasmids were transiently transfected into 293 T cells along with miR-125b mimics or a negative control. The luciferase reporter assay was used to validate whether the predicted MCL1 gene is a direct target of miR-125b. The HTR8/SVneo cells were transfected with miR-125 mimics, inhibitors, or a scramble control. Real-time polymerase chain reaction and western blotting were used to analyze mRNA and protein expression of the target gene MCL1. Flow cytometry was used to determine the effects on apoptosis. The luciferase activity assay validated the ability of miR-125b to specifically attenuate MCL1 transcription in the 293 T cell line, suggesting that MCL1 is a direct target of miR-125b. After transfection by miR-125b, relative expression and translation of the target gene MCL1 mRNA were repressed in HTR-8/SVneo cells. Trophoblast cells were induced to undergo apoptosis by overexpressing miR-125b in the HTR-8/SVneo cell line. In conclusion, MiR-125b may induced apoptosis of HTR8/SVneo cells by targeting MCL1. Our findings suggest that miR-125b may play a pivotal role in the pathophysiology of placentation.

LRP6 Knockdown Ameliorates Insulin Resistance via Modulation of Autophagy by Regulating GSK3ß Signaling in Human LO2 Hepatocytes.

Recent studies suggest that autophagy is highly involved in insulin resistance (IR). Inhibition of the PI3K/AKT/mTOR signaling pathway induces autophagy activation. Additionally, depletion of LRP6 has been shown to increase insulin sensitivity but its mechanism is still not clear. We hypothesized that LRP6 contributes to IR by regulating mTOR mediated autophagy through GSK3ß in hepatocytes. LO2 hepatocytes were treated with palmitate (PA) and insulin to induced IR. Levels of LRP6 mRNA and protein expression were measured by real time-PCR and western blot analysis. LRP6 knock down was achieved by adenovirus mediated Si-LRP6 expression and its roles in IR, glucose, GSK3ß, mTOR signaling, and autophagy were explored. Finally, GSK3ß was overexpressed and its involvement in autophagy and IR was examined. We found that PA treatment led to a reduced glucose uptake and IR in hepatocytes, which was accompanied by an upregulation of LRP6 expression. Knocking down of LRP6 enhanced glucose uptake and insulin sensitivity in PA treated cells, probably through increasing GSK3b activity. Overexpression of GSK3b mimicked LRP6 reduction by enhancing autophagy and ameliorating IR. Our study revealed a significant molecular mechanism connecting LRP6 to insulin sensitivity through GSK3ß-mTOR mediated autophagy.

Variants in the 5'-UTR of APELA gene in women with preeclampsia.

OBJECTIVE: To detect APELA gene variants in clinical cases with preeclampsia (PE) and evaluate the influence of the APELA variants in gene expression. METHOD: A total of 288 individuals suffering from PE and 384 unaffected individuals were chosen for case-control studies. Genomic DNA was extracted from peripheral blood. Variants screening of APELA gene was conducted, and potential influence of variants in APELA expression was evaluated with a luciferase assay. RESULTS: Two rare variants (c.-306A > G and c.-145A > G) in the 5'-UTR of APELA gene were identified exclusively in PE affected individuals. Luciferase assays in HEK293 cells and HTR-8/SVneo cells revealed that both variants impaired transcriptional activity of APELA by altering the function of promoter region. Also, a single-nucleotide polymorphism (SNP) (c.159 T > C) in exon 2 of APELA was found in both cases and controls, and there was no statistically significant difference in genotype and allele frequency between cases and controls. CONCLUSION: Variants in the 5'-UTR of APELA gene may account for variability of APELA expression among individuals with PE and may play a negative regulatory role in the pathogenesis of PE.

Association study between variants in LHCGR DENND1A and THADA with preeclampsia risk in Han Chinese populations.

Objective: To evaluate the association between preeclampsia and three single nucleotide polymorphisms (rs13405728 in LHCGR gene; rs13429458 in THADA gene, and rs2479106 in DENND1A gene) which were identified to be genetic variants of polycystic ovary syndrome (PCOS) by genome-wide association study in Han Chinese populations. Methods: A total of 784 northern Han Chinese women (378 controls and 406 cases) were genotyped for the three genetic variants by polymerase chain reaction and direct sequencing. Unconditional logistic regression analysis was used to adjust the impact of prepregnancy body mass index, primiparas, and maternal age. Results: No significant difference was found in the allele frequencies of the three genetic variants between cases and controls (p > .05), but genotype frequency of the SNP rs2479106 was significantly differ between cases and controls when analyzed under recessive models (p = .02). There was also a substantial difference in the genotype frequencies of the SNP rs13429458 between cases and controls under additive models (p = .01). Conclusions: Genetic variants of PCOS (rs13405728 in LHCGR gene; rs13429458 in THADA gene and rs2479106 in DENND1A gene) may not be involved in the development of preeclampsia in Han Chinese women.

Low-Density Lipoprotein Receptor-Related Protein 6 Is Essential for Trophoblast Survival and Invasion.

Remodeling of maternal spiral artery after the implantation of embryo relies on tightly regulated trophoblast functions and is pivotal to ensure the success of pregnancy. Low-density lipoprotein receptor-related protein 6 (LRP6) is implicated in angiogenesis and several vascular diseases, but its function in trophoblast regulation is still not fully understood. We aimed to investigate the involvement of LRP6 in trophoblast functions during maternal spiral artery remodeling. HTR-8/SVneo cells, a trophoblast cell line, were employed to examine the impact of LRP6 knockdown on proliferation, apoptosis, and migration, as well as invasion and tube formation. Expression of matrix metalloproteinases (MMPs), angiogenic factors placental growth factor (PlGF), and vascular endothelial growth factor (VEGF), as well as activation of canonical Wnt/ß-catenin signaling pathway, which was involved in artery remodeling process, was also analyzed. Lipoprotein receptor-related protein 6 knockdown suppressed proliferation, migration, invasion, and tube formation, as well as induced apoptosis in HTR-8/SVneo cells. In addition, LRP6 knockdown also significantly decreased expression of MMPs, PlGF, and VEGF and activation of Wnt/ß-catenin signaling pathway. Lipoprotein receptor-related protein 6 might positively regulate the remodeling of the maternal artery through both endovascular formation and trophoblast invasion.

microRNA-96 protects pancreatic ß-cell function by targeting PAK1 in gestational diabetes mellitus.

Gestational diabetes mellitus (GDM) is a disease condition in which a woman develops high blood sugar levels during pregnancy, which might be induced by multiple factors. Among those relative factors, microRNA (miRNA) is well-known to be involved in GDM development. In this study, we investigated the role of miRNA in GDM by analyzing miRNA expression profiling in placenta tissues from healthy or GDM pregnancies. We found that miR-96 was the most down-regulated miRNA in GDM samples. Furthermore, miRNA target gene prediction revealed that p21-activated kinase 1 (PAK1) is a potential target of miR-96. Functional assays showed that miR-96 enhanced ß-cell function, whereas PAK1 inhibited ß-cell function and cell viability. Our findings demonstrate that miR-96 plays a critical role in GDM development by regulating PAK1 expression, insulin secretion, and ß-cell function. © 2018 BioFactors, 44(6):539-547, 2018.

MicroRNA-200 and microRNA-30 family as prognostic molecular signatures in ovarian cancer: A meta-analysis.

BACKGROUND: MicroRNAs (miRs) play a vital role in the occurrence, development, and progression of human cancers, but its role in the prognosis of ovarian cancer is unclear. METHODS: We performed a meta-analysis by searching PubMed, Embase, and Web of Science databases for eligible studies. The pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were used to explore the association between miRs expression and overall survival (OS) and progression-free survival (PFS) on ovarian cancer patients. We also used Kaplan-Meier to analyze the relationship between miRs and OS in OncoLnc dataset. RESULTS: A total of 15 records were included into the meta-analysis. The expression level of miR-200 family showed significant association with OS (HR = 0.78, 95% CI: 0.64-0.94) and insignificant association with PFS (HR = 0.72, 95% CI: 0.50-1.03). Subgroup analysis revealed that an increased expression level of miR-200c was associated with better OS (HR = 0.59, 95% CI: 0.45-0.74). An increased expression level of miR-200a, miR-200c, and miR-141 was associated with better PFS (miR-200a, HR = 0.59, 95% CI: 0.42-0.75; miR-200c, HR = 0.50, 95% CI: 0.14-0.87, miR-141, HR = 0.38, 95% CI: 0.12-0.63). Similarly, higher expression of miR-30 family was associated with elevated OS/PFS for ovarian cancer (OS, HR = 0.43, 95% CI: 0.13-0.74; PFS, HR = 0.76, 95% CI: 0.64-0.87). The OncoLnc dataset presented that elevated expression level of miR-30d-5p was associated with better OS (n = 470, P = .0197). CONCLUSION: The meta-analysis reveals that miR-200 family and miR-30 family could be promising prognostic biomarkers of ovarian cancer.

Ferulic acid alleviates symptoms of preeclampsia in rats by upregulating vascular endothelial growth factor.

Preeclampsia is a complication affecting pregnant women worldwide, which leads to maternal and fetal morbidity and mortality. In this study, we evaluated the efficacy of ferulic acid (FA) on an Nω -nitro-L-arginine methyl ester hydrochloride (L-NAME) induced rat model of preeclampsia. L-NAME was administered to pregnant rats to induce preeclampsia. 48 rats were divided into three experimental groups (n=16 each): control group, preeclampsia group and preeclampsia with FA treatment (preeclampsia+FA). Physiological characteristics such as urine volume, total urine protein and blood pressure were assessed. Expressions levels of urinary nephrin and podocin mRNAs were analyzed by RT-PCR. Levels of renal vascular endothelial growth factor (VEGF), renal soluble fms-like tyrosine kinase-1 (sFlt-1) and serum placenta growth factor (PlGF) were also examined. Urine volume, total urine protein and blood pressure were markedly increased in preeclampsia group rats compared to control (P<.05), which were then significantly reduced in preeclampsia+FA group (P<.05). Expressions of urinary nephrin and podocin mRNAs, levels of VEGF, sFlt-1 and PlGF were also reversed in preeclampsia+FA group compared to preeclampsia rats (P<.05). We hereby report for the first time, FA alleviates preeclampsia symptoms in a rat preeclampsia model, supporting its potential value in treating preeclampsia.

Role of UMOD Promoter Polymorphism in the Etiology of Preeclampsia.

AIMS: To evaluate the association between preeclampsia (PE) and the single nucleotide polymorphism (SNP) rs13333226, located in the promoter region of the UMOD gene. METHODS: A total of 1248 pregnant Han Chinese women (716 controls and 532 patients with PE) were included in this study. Genotyping of the rs13333226 polymorphism was performed by real-time PCR using a TaqMan-minor groove binder (MGB) probe assay. RESULTS: No significant differences were detected in the allele (p = 0.62, OR = 1.08, 95% CI = 0.81-1.44) and genotype frequencies of rs13333226 (padditive = 0.38, pdominant = 0.45, precessive = 0.31) between cases and controls. When patients were divided into subgroups, no association was found with mild preeclampsia (M PE), severe preeclampsia (S PE), early onset PE, or late-onset PE. Furthermore, no significant differences were detected in the genotype and allele frequencies of rs1333226 between patients with M PE and S PE (p > 0.05) or between patients with late and early onset of the disease (p > 0.05). CONCLUSIONS: UMOD rs13333226 does not appear to be associated with PE in Han Chinese women.

Resveratrol relieves gestational diabetes mellitus in mice through activating AMPK.

BACKGROUND: Gestational diabetes mellitus (GDM) is a disease often manifests in mid to late pregnancy with symptoms including hyperglycemia, insulin resistance and fetal mal-development. The C57BL/KsJ-Lep (db/+) (db/+) mouse is a genetic GDM model that closely mimicked human GDM symptoms. Resveratrol (RV) is a naturally existing compound that has been reported to exhibit beneficial effects in treating type-2 diabetes. METHODS: In this study, we investigated the effect of RV on the pregnant db/+ GDM mouse model, and the underlying molecular mechanism. RESULTS: RV greatly improved glucose metabolism, insulin tolerance and reproductive outcome of the pregnant db/+ females. Moreover, we found that RV relieved GDM symptoms through enhancing AMPK activation, which in turn reduced production and activity of glucose-6-phosphatase in both pregnant db/+ females and their offspring. CONCLUSIONS: Our findings further supported the potential therapeutic effect of RV on not only diabetes, but also alleviating GDM.