Management strategies and outcomes in pregnancy-related acute aortic dissection: a multicentre cohort study in China.

BACKGROUND: Acute aortic dissection (AD) in pregnancy poses a lethal risk to both mother and fetus. However, well-established therapeutic guidelines are lacking. This study aimed to investigate clinical features, outcomes and optimal management strategies for pregnancy-related AD. METHODS: We conducted a retrospective multicentre cohort study including 67 women with acute AD during pregnancy or within 12 weeks postpartum from three major cardiovascular centres in China between 2003 and 2021. Patient characteristics, management strategies and short-term outcomes were analysed. RESULTS: Median age was 31 years, with AD onset at median 32 weeks gestation. Forty-six patients (68.7%) had type A AD, of which 41 underwent immediate surgery. Overall maternal mortality was 10.4% (7/67) and fetal mortality was 26.9% (18/67). Compared with immediate surgery, selective surgery was associated with higher risk of composite maternal and fetal death (adjusted RR: 12.47 (95% CI 3.26 to 47.73); p=0.0002) and fetal death (adjusted RR: 8.77 (95% CI 2.33 to 33.09); p=0.001). CONCLUSIONS: Immediate aortic surgery should be considered for type A AD at any stage of pregnancy or postpartum. For pregnant women with AD before fetal viability, surgical treatment with the fetus in utero should be considered. Management strategies should account for dissection type, gestational age, and fetal viability. TRIAL REGISTRATION NUMBER: NCT05501145.

Ganoderic acid D prevents oxidative stress-induced senescence by targeting 14-3-3ε to activate CaM/CaMKII/NRF2 signaling pathway in mesenchymal stem cells.

Stem cell senescence is an important cause of aging. Delaying senescence may present a novel way to combat aging and age-associated diseases. This study provided a mechanistic insight into the protective effect of ganoderic acid D (GA-D) against human amniotic mesenchymal stem cell (hAMSCs) senescence. GA-D, a Ganoderma lucidum-derived triterpenoid, markedly prevented hAMSCs senescence via activating the Ca2+ calmodulin (CaM)/CaM-dependent protein kinase II (CaMKII)/nuclear erythroid 2-related factor 2 (Nrf2) axis, and 14-3-3ε was identified as a target of GA-D. 14-3-3ε-encoding gene (YWHAE) knockdown in hAMSCs reversed the activation of the CaM/CaMKII/Nrf2 signals to attenuate the GA-D anti-aging effect and increase senescence-associated ß-galactosidase (SA-ß-gal), p16 and p21 expression levels, including reactive oxygen species (ROS) production, thereby promoting cell cycle arrest and decreasing differentiation potential. YWHAE overexpression maintained or slightly enhanced the GA-D anti-aging effect. GA-D prevented d-galactose-caused aging in mice by significantly increasing the total antioxidant capacity, as well as superoxide dismutase and glutathione peroxidase activity, and reducing the formation of malondialdehyde, advanced glycation end products, and receptor of advanced glycation end products. Consistent with the protective mechanism of GA-D against hAMSCs senescence, GA-D delayed the senescence of bone-marrow mesenchymal stem cells in this aging model in vivo, reduced SA-ß-gal and ROS production, alleviated cell cycle arrest, and enhanced cell viability and differentiation via regulating 14-3-3ε and CaM/CaMKII/Nrf2 axis. Therefore, GA-D retards hAMSCs senescence by targeting 14-3-3ε to activate the CaM/CaMKII/Nrf2 signaling pathway. Furthermore, the in vivo GA-D anti-aging effect may involve the regulation of stem cell senescence via the same signal axis.

The role of insulin-like growth factor 2 mRNA binding proteins in female reproductive pathophysiology.

Insulin-like growth factor 2 (IGF2) mRNA binding proteins (IMPs) family belongs to a highly conserved family of RNA-binding proteins (RBPs) and is responsible for regulating RNA processing including localization, translation and stability. Mammalian IMPs (IMP1-3) take part in development, metabolism and tumorigenesis, where they are believed to play a major role in cell growth, metabolism, migration and invasion. IMPs have been identified that are expressed in ovary, placenta and embryo. The up-to-date evidence suggest that IMPs are involved in folliculogenesis, oocyte maturation, embryogenesis, implantation, and placentation. The dysregulation of IMPs not only contributes to carcinogenesis but also disturbs the female reproduction, and may participate in the pathogenesis of reproductive diseases and obstetric syndromes, such as polycystic ovary syndrome (PCOS), pre-eclampsia (PE), gestational diabetes mellitus (GDM) and gynecological tumors. In this review, we summarize the role of IMPs in female reproductive pathophysiology, and hope to provide new insights into the identification of potential therapeutic targets.

LAWN TRIMMER-RELATED OPEN-GLOBE INJURIES IN TAIWAN.

PURPOSE: Work-related ocular trauma remains the leading cause of unilateral visual impairment worldwide. Many preventable work-related ocular injuries continue to occur, even at home. This study describes the characteristics, surgical techniques, and prognostic factors of lawn trimmer-related open-globe injuries in eastern Taiwan. METHODS: This was a retrospective, consecutive case series study. Slit-lamp biomicroscopy, dilated fundoscopy, and orbital computed tomography (CT) images were collected. RESULTS: Twenty-six eyes of 26 patients were enrolled in the study. Fifteen patients (57.7%) had an intraocular foreign body (IOFB). The IOFB was metallic in 13 cases and glass and stone in the other 2 cases. Seven IOFBs (46.7%) were retained in the anterior chamber, 7 (46.7%) in the posterior segment, and 1 (6.7%) in the intraconal space. Univariate analysis showed that the presence of IOFB trended toward the development of endophthalmitis; however, this was not statistically significant (hazard ratio, 2.25; 95% confidence interval 0.35-14.61; P = 0.658). Eleven patients had metallic IOFBs noted on CT scans with metal artifacts, whereas two patients had small metallic IOFBs without metal artifacts. One patient had a glass IOFB mimicking metal artifacts on the CT scan. In one case, CT failed to reveal the IOFB, and an intralenticular metallic foreign body was incidentally found intraoperatively. CONCLUSION: Our study provides a broad characterization of lawn trimmer-related open-globe injuries. The informative and diverse findings of IOFBs on CT scans will help clinicians detect and recognize IOFBs more precisely and perform the surgery without causing further damage.

Oxidative Transformation of Dihydroflavonols and Flavan-3-ols by Anthocyanidin Synthase from Vitis vinifera.

Twelve polyphenols from three distinct families (dihydroflavonols, flavan-3-ols, and flavanones) were studied as potential substrates of anthocyanidin synthase from Vitis vinifera (VvANS). Only flavan-3-ols of (2R,3S) configuration having either a catechol or gallol group on ring B are accepted as substrates. Only dihydroflavonols of (2R,3R) configuration are accepted as substrates, but a catechol or gallol group is not mandatory. Flavanones are not substrates of VvANS. HPLC and MS/MS analyses of the enzymatic products showed that the VvANS-catalyzed oxidative transformation of (+)-dihydroflavonols, such as dihydroquercetin, dihydrokaempferol and dihydromyricetin, leads only to the corresponding flavonols. Among the flavan-3-ols recognized as substrates, (+)-gallocatechin was only transformed into delphinidin by VvANS, whereas (+)-catechin was transformed into three products, including two major products that were an ascorbate-cyanidin adduct and a dimer of oxidized catechin, and a minor product that was cyanidin. Data from real-time MS monitoring of the enzymatic transformation of (+)-catechin suggest that its products are all derived from the initial C3-hydroxylation intermediate, i.e., a 3,3-gem-diol, and their most likely formation mechanism is discussed.

Pomegranate peel-derived punicalagin: Ultrasonic-assisted extraction, purification, and its α-glucosidase inhibitory mechanism.

The pomegranate peel is a by-product of pomegranate fruit rich in polyphenols. In this study, pomegranate peel polyphenols were explored using LC-MS/MS, and punicalagin was the most abundant compound. The highest yield (505.89 ± 1.73 mg/g DW) of punicalagin was obtained by ultrasonic-assisted extraction (UAE) with the ethanol concentration of 53%, sample-to-liquid ratio of 1:25 w/v, ultrasonic power of 757 W, and extraction time of 25 min. Punicalagin was further purified by the macroporous resin D101 and prep-HPLC, reaching the purity of 92.15%. The purified punicalagin had the IC50 of 82 ± 0.02 µg/mL against α-glucosidase, similar to the punicalagin standard with IC50 of 58 ± 0.014 µg/mL, both exhibiting a mixed inhibitory mechanism. Molecular docking further revealed that a steric hindrance with the intermolecular energy of -7.99 kcal/mol was formed between punicalagin and α-glucosidase. Overall, pomegranate peel is a promising source of punicalagin to develop anti-diabetic functional foods.

The anticancer potential of the dietary polyphenol rutin: Current status, challenges, and perspectives.

Rutin is one of the most common dietary polyphenols found in vegetables, fruits, and other plants. It is metabolized by the mammalian gut microbiota and absorbed from the intestines, and becomes bioavailable in the form of conjugated metabolites. Rutin exhibits a plethora of bioactive properties, making it an extremely promising phytochemical. Numerous studies demonstrate that rutin can act as a chemotherapeutic and chemopreventive agent, and its anticancer effects can be mediated through the suppression of cell proliferation, the induction of apoptosis or autophagy, and the hindering of angiogenesis and metastasis. Rutin has been found to modulate multiple molecular targets involved in carcinogenesis, such as cell cycle mediators, cellular kinases, inflammatory cytokines, transcription factors, drug transporters, and reactive oxygen species. This review summarizes the natural sources of rutin, its bioavailability, and in particular its potential use as an anticancer agent, with highlighting its anticancer mechanisms as well as molecular targets. Additionally, this review updates the anticancer potential of its analogs, nanoformulations, and metabolites, and discusses relevant safety issues. Overall, rutin is a promising natural dietary compound with promising anticancer potential and can be widely used in functional foods, dietary supplements, and pharmaceuticals for the prevention and management of cancer.

Green Extraction of Antioxidant Polyphenols from Green Tea (Camellia sinensis).

In this study, the feasibility of improving the extraction yield of green tea antioxidant polyphenols by the combination of ultrasound-assisted extraction (UAE) and deep eutectic solvents (DESs) was investigated. Choline chloride (ChCl)-glycerol was selected as the best DES among 12 ChCl-based DESs to extract tea antioxidant polyphenols. Subsequently, the influences of extraction parameters on total phenolic content (TPC) values were investigated, and liquid/solid ratio, ultrasonic power, and ultrasonic time were optimized based on the response surface methodology. The optimal extraction conditions were a liquid to solid ratio of 36:1 (mL/g), ultrasonic power of 461.5 W, and ultrasonic time of 21 min, with the highest TPC value of 243 ± 7 mg gallic acid equivalent (mg GAE)/g dry weight (DW), which was 13% higher than that before optimization. In addition, under the optimal extraction conditions, tea polyphenolic extract exhibited higher antioxidant activity compared with conventional extraction methods. Four major catechins in the green tea extracts, including (-)-epicatechin (EC), (-)-epigallocatechin (EGC), (-)-epicatechin gallate (ECG) and (-)-epigallocatechin gallate (EGCG) were identified and quantified by high-performance liquid chromatography. In addition, scanning electron microscopy (SEM) analysis revealed that UAE-DES effectively disrupted the green tea leaf cells, thereby improving tea polyphenol yield. In summary, UAE-DES is an ideal green extraction method for the extraction of tea antioxidant polyphenols.

Optimization and Characterization of Microwave-Assisted Hydro-Distillation Extraction of Essential Oils from Cinnamomum camphora Leaf and Recovery of Polyphenols from Extract Fluid.

In this study, the efficiency of microwave-assisted hydro-distillation (MAHD) to extract essential oil from Cinnamomum camphora leaf, and the recovery of polyphenols from extract fluid were investigated. The effects of microwave power, liquid-to-material ratio, and extraction time on the extraction efficiency were studied by a single factor test as well as the response surface methodology (RSM) based on the central composite design method. The optimal extraction conditions were a microwave power of 786.27 W, liquid-to-material ratio of 7.47:1 mL/g, and extraction time of 35.57 min. The yield of essential oil was 3.26 ± 0.05% (w/w), and the recovery of polyphenols was 4.97 ± 0.02 mg gallic acid equivalent/g dry weight under the optimal conditions. Furthermore, the comprehensive two-dimensional gas chromatography-time-of-flight mass spectrometry (GC×GC-TOFMS) was used to characterize the essential oils of fresh and fallen leaves, and 159 individual compounds were tentatively identified, accounting for more than 89.68 and 87.88% of the total contents, respectively. The main ingredients include sabinene, l-ß-pinene, ß-myrcene, α-terpineol, 3-heptanone, and ß-thujene, as well as δ-terpineol and 3-heptanone, which were first identified in C. camphora essential oil. In conclusion, the MAHD method could extract essential oil from C. camphora with high efficiency, and the polyphenols could be obtained from the extract fluid at the same time, improving the utilization of C. camphora leaf.

Termination of a partial hydatidiform mole and coexisting fetus: A case report.

BACKGROUND: We describe the treatment strategy for a patient who was found to have a partial hydatidiform mole and coexisting fetus (PHMCF) during the second trimester. The patient was a 38-year-old Chinese woman who had become pregnant following in vitro fertilization and embryo transplantation. We wanted to determine the safest therapeutic strategy to terminate the PHMCF during the second trimester. CASE SUMMARY: In this case, we present a patient who was found to have a PHMCF complicated with serious continuous vaginal bleeding and pre-eclampsia during the second trimester. After careful evaluation, the pregnancy was considered to be unsustainable and was terminated via caesarean section (CS). An infant with weak vital signs and a partially cystic placenta measuring 110 mm × 95 mm × 35 mm were delivered by CS. The patient was discharged after 4 d. The serum levels of ß-human chorionic gonadotropin decreased to within a normal range 5 wk after the operation, and no evidence of persistent trophoblastic disease or lung metastases was noticed at the 6-mo follow-up. CONCLUSION: CS termination of PHMCF during the second trimester may be a relatively safe therapeutic strategy.

mTORC2 activation protects retinal ganglion cells via Akt signaling after autophagy induction in traumatic optic nerve injury.

Traumatic optic neuropathy is an injury to the optic nerve that leads to vision loss. Autophagy is vital for cell survival and cell death in central nervous system injury, but the role of autophagy in traumatic optic nerve injury remains uncertain. Optic nerve crush is a robust model of traumatic optic nerve injury. p62 siRNA and rapamycin are autophagy inducers and have different neuroprotective effects in the central nervous system. In this study, p62 and rapamycin induced autophagy, but only p62 siRNA treatment provided a favorable protective effect in visual function and retinal ganglion cell (RGC) survival. Moreover, the number of macrophages at the optic nerve lesion site was lower in the p62-siRNA-treated group than in the other groups. p62 siRNA induced more M2 macrophage polarization than rapamycin did. Rapamycin inhibited both mTORC1 and mTORC2 activation, whereas p62 siRNA inhibited only mTORC1 activation and maintained mTORC2 and Akt activation. Inhibition of mTORC2-induced Akt activation resulted in blood-optic nerve barrier disruption. Combined treatment with rapamycin and the mTORC2 activator SC79 improved RGC survival. Overall, our findings suggest that mTORC2 activation after autophagy induction is necessary for the neuroprotection of RGCs in traumatic optic nerve injury and may lead to new clinical applications.

Polyphenolic Profile and Antioxidant Capacity of Extracts from Gordonia axillaris Fruits.

An ultrasonic-assisted extraction (UAE) method was adopted to extract natural antioxidants from edible Gordonia axillaris fruit. Single-factor experiments and response surface methodology were conducted to investigate the influences of five different parameters on antioxidant capacity. The optimal conditions of the UAE were 39.78% ethanol, 30.94 mL/g solvent/material ratio, 59.47 min extraction time, 40 °C temperature, and 400 W ultrasonication power. The antioxidant capacity was 525.05 ± 14.34 µmol Trolox/g DW under the optimal conditions, which was in agreement with the predicted one (531.71 µmol Trolox/g DW). Additionally, in comparison with two traditional methods (maceration and Soxhlet extraction), the established UAE method greatly improved the yield of antioxidants and significantly reduced the extraction time. Besides, nine phenolic compounds were identified and quantified in the extract of Gordonia axillaris fruits by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS), including rutin, gallic acid, protocatechuic acid, epicatechin, 2-hydrocinnamic acid, p-coumaric acid, quercetin, epicatechin gallate, and ferulic acid. The richness of phenolic compounds in the Gordonia axillaris fruits indicated its potential health benefits, and its extract rich in antioxidants could be developed into functional food or nutraceuticals with the potential to prevent certain diseases induced by oxidative stress, such as cardiovascular diseases and cancers. This study also provided a way to enhance the economic values of Gordonia axillaris fruits compared to raw fruits.

Epigenetic inactivation of BRCA1 through promoter hypermethylation in ovarian cancer progression.

AIM: The BRCA1 promoter is hypermethylated in ovarian cancer patients. We postulated that this hypermethylation might be involved in ovarian cancer progression. METHODS: To confirm our hypothesis, tissue and serum samples were collected from ovarian carcinoma patients and categorized according to tumor stage. Healthy or benign ovarian disease tissue samples and corresponding serum samples were used as controls. Breast and ovarian cancer susceptibility gene 1 (BRCA1) promoter methylation levels were detected by real-time polymerase chain reaction (PCR). Real-time PCR was also used to evaluate BRCA1 gene expression, and Western blot was performed to assay the expression of BRCA1 protein. RESULTS: BRCA1 showed hypomethylation in 30 normal ovarian and 30 benign ovarian tumors, but showed hypermethylation or methylation in ovarian cancer patients. There was also a significant difference in the BRCA1 promoter methylation levels between different ovarian cancer stages. Compared to stage I and the control groups, there were higher BRCA1 promoter methylation frequencies in stage II and III ovarian cancers. BRCA1 methylation correlated with the loss of BRCA1 expression. BRCA1 promoter in stage I tumors showed hypomethylated. CONCLUSION: Promoter hypermethylation may act as a biomarker for sporadic ovarian cancer progression, but is unlikely to be helpful in the early diagnosis of ovarian cancer.

Aberrant methylation of breast and ovarian cancer susceptibility gene 1 in chemosensitive human ovarian cancer cells does not involve the phosphatidylinositol 3'-kinase-Akt pathway.

Methylation is an important silencing mechanism of breast and ovarian cancer susceptibility gene 1 (BRCA1) expression in sporadic ovarian cancer. However, the role of BRCA1 methylation in chemotherapy in sporadic ovarian cancer and the related pathways have not been understood completely. This study has determined the roles of BRCA1 hypermethylation in chemotherapy of sporadic ovarian cancer and its related signaling pathways. We used bisulfite sequencing, real-time polymerase chain reaction, and western blotting to check the methylation state and expression levels of BRCA1 of the following cell lines: platinum-sensitive human ovarian cancer cell line COC1, platinum-resistant cell line COC1/DDP, SKOV-3, and 5-Aza-dC treated COC1. The cisplatin sensitivity of ovarian cancer cells was examined by MTS (methyl-thiazol tetrazolium) assay. Tumorigenicity in vivo and DDP-based chemosensitivity were compared among the above cells. Phosphatidylinositol 3'-kinase (PI3K)-Akt pathway activation in ovarian cancer cells was studied by western blotting. The frequency of BRCA1 methylation in the COC1 cell line was higher than in COC1/DDP and SKOV-3 cell lines, whereas the mRNA and protein expression of BRCA1 were lower than in the COC1/DDP and SKOV-3 cell lines. DNA demethylation decreased the chemosensitivity of COC1 cells and partially increased the expression levels of BRCA1. The activation of the PI3K-Akt pathway was low in ovarian cancer cells. Our results indicate that hypermethylation of BRCA1 might play an important role in the chemosensitivity of ovarian cancer, and that the PI3K-Akt pathway is not involved in this response.

The role of microRNAs in ovarian cancer initiation and progression.

Epithelial ovarian cancer (EOC) has the highest mortality rate of all gynaecological cancers. One of the greatest impediments to improving outcome is an incomplete understanding of the molecular underpinnings of EOC pathogenesis and progression. Recent studies suggest that microRNAs (miRNAs) are involved in ovarian tumorigenesis and cancer development. Several miRNA profiling studies have identified some consensus aberrantly expressed miRNAs in EOC tissues, and these EOC-related miRNAs may play critical roles in the pathogenesis and progression of EOC. Moreover, some of the miRNAs may have diagnostic or prognostic significance. In this review, recent progress to reveal the role of miRNAs in EOC will be addressed, and a model for miRNA functions in ovarian cancer initiation and progression will be proposed.