StMAPKK5 Positively Regulates Response to Drought and Salt Stress in Potato.

MAPKKs, as one of the main members of the mitogen-activated protein kinase (MAPK) cascade pathway, are located in the middle of the cascade and are involved in many physiological processes of plant growth and development, as well as stress tolerance. Previous studies have found that StMAPKK5 is responsive to drought and salt stress. To further investigate the function and regulatory mechanism of StMAPKK5 in potato stress response, potato variety 'Atlantic' was subjected to drought and NaCl treatments, and the expression of the StMAPKK5 gene was detected by qRT-PCR. StMAPKK5 overexpression and RNA interference-mediated StMAPKK5 knockdown potato plants were constructed. The relative water content, superoxide dismutase (SOD), catalase (CAT), and peroxidase (POD) activities, as well as proline (Pro) and malondialdehyde (MDA) contents of plant leaves, were also assayed under drought and NaCl stress. The StMAPKK5 interacting proteins were identified and validated by yeast two-hybrid (Y2H) and bimolecular fluorescence complementation (BiFC). The results showed that the expression of StMAPKK5 was significantly up-regulated under drought and NaCl stress conditions. The StMAPKK5 protein was localized in the nucleus, cytoplasm, and cell membrane. The expression of StMAPKK5 affected the relative water content, the enzymatic activities of SOD, CAT, and POD, and the proline and MDA contents of potatoes under drought and salt stress conditions. These results suggest that StMAPKK5 plays a significant role in regulating drought and salt tolerance in potato crop. Yeast two-hybrid (Y2H) screening identified four interacting proteins: StMYB19, StZFP8, StPUB-like, and StSKIP19. BiFC confirmed the authenticity of the interactions. These findings suggest that StMAPKK5 is crucial for potato growth, development, and response to adversity.

Establishment and Reliability Evaluation of Prognostic Models in Diabetic Foot.

Purpose: To study the risk factors affecting amputation and survival in patients with diabetic foot (DF) and to construct a predictive model using the machine learning technique for DF foot amputation and survival and evaluate its effectiveness. Materials and Methods: A total of 200 patients with DF hospitalized in the First Affiliated Hospital of Shantou University Medical College in China were selected via cluster analysis screening, Kaplan-Meier survival calculation, amputation rate and Cox proportional hazards model investigation of risk factors associated with amputation and death. In addition, we constructed various models, including Cox proportional hazards regression analysis, the deep learning method convolution neural network (CNN) model, backpropagation (BP) neural network model, and backpropagation neural network prediction model after optimizing the genetic algorithm. The accuracy of the 4 prediction models for survival and amputation was assessed, and we evaluated the reliability of these computational models based on the size of the area under the ROC curve (AUC), sensitivity and specificity. Results: We found that the 1-year survival rate in patients with DF was 88.5%, and the 1-year amputation rate was 12.5%. Wagner's Classification of Diabetic Foot Ulcers grade, ankle-brachial index (ABI), low-density lipoprotein (LDL), and percutaneous oxygen partial pressure (TcPO2) were independent risk factors for amputation in patients with DF, while cerebrovascular disease, Sudoscan sweat gland function score, glycated hemoglobin (HbA1c) and peripheral artery disease (PAD) were independent risk factors for death in patients with DF. In addition, our results showed that in the case of amputation, the COX regression predictive model revealed an AUC of 0.788, sensitivity of 74.1% and specificity of 83.6%. The BP neural network predictive model identified an AUC of 0.874, sensitivity of 87.0% and specificity of 87.7%. An AUC of 0.909, sensitivity of 90.7% and specificity of 91.1% were found after optimizing the BP neural network prediction model via genetic algorithm. In the deep learning CNN model, the AUC, sensitivity and specificity were 0.939, 92.6%, and 95.2%, respectively. In the analysis of risk factors for death, the COX regression predictive model identified the AUC, sensitivity and specificity as 0.800, 74.1% and 85.9%, respectively. The BP neural network predictive model revealed an AUC, sensitivity and specificity of 0.937, 93.1% and 94.4%, respectively. Genetic algorithm-based optimization of the BP neural network predictive model identified an AUC, sensitivity and specificity of 0.932, 91.4% and 95.1%, respectively. The deep learning CNN model found the AUC, sensitivity and specificity to be 0.861, 82.8% and 89.4%, respectively. Conclusion: To identify risk factors for death, the BP neural network predictive model and genetic algorithm-based optimizing BP neural network predictive model have higher sensitivity and specificity than the deep learning method CNN predictive model and COX regression analysis.

Cytotoxic tetronic acid derivatives from the mangrove endophytic fungus Hypomontagnella monticulosa YX702.

Three new tetronic acid derivatives, nodulisporacid A ethyl ester (3), isosporothric acid methyl ester (4), and (R)-3-(methoxycarbonyl)-2-methyleneundecanoic acid (5) were isolated from mangrove endophytic fungus Hypomontagnella monticulosa YX702, together with three known analogues nodulisporacid A (1), nodulisporacid A methyl ester (2), and dihydrosporothriolide (6). The structures of these new compounds were elucidated by analysis of NMR and HR-ESI-MS spectroscopic data. In addition, the absolute configuration of nodulisporacid A (1) was confirmed by single-crystal X-ray diffraction for the first time. Subsequently, the absolute configuration of compounds 2 and 3 were determined by chemical derivatization of nodulisporacid A (1). The absolute configuration of compound 4 and 5 were established by TDDFT ECD calculations. Compounds 1 and 2 exhibited cytotoxic activities against A549 and Hela cancer cell lines with the IC50 values between 5.64 and 8.14 µM.

Dupilumab for Treatment of Food-Dependent, Exercise-Induced Anaphylaxis: Report of One Case.

Food-dependent, exercise-induced anaphylaxis (FDEIA) is a potentially life-threatening disorder that often occurs with exercise, and patients typically have eaten a specific food within hours before disease onset. This disease is exceedingly rare, with a prevalence of 0.02%. No well-recognized prevention or treatment strategy has been available for FDEIA except avoiding triggers strictly. Here we report an 11-year-old boy with a history of recurrent anaphylaxis of unknown etiology more than 10 times within two years. As the anaphylactic symptoms had not been controlled after traditional treatments, the patient was given subcutaneous injection of dupilumab seven times within 33 weeks. During dupilumab treatments, the patient was exposed to culprit mushrooms plus exercises at least twice a month but without notable anaphylaxis. Thus, Dupilumab may improve the allergic reactions in FDEIA patients.

Structurally diverse glycosides with α-glucosidase inhibitory properties from water extract of the leaves of Cyclocarya paliurus.

In this work we investigated the chemical constituents of water extract of the leaves of Cyclocarya paliurus. Two new megastigmane glycosides (3 and 8), three aliphatic alcohol glycosides (9-11), and two aromatic glycosides (12 and 13), along with fourteen known compounds were isolated, and their in vitro inhibitory activity against α-glucosidase was evaluated. Compounds 13 and 15-18 displayed inhibitory activity with IC50 values varying from 27.05 to 96.58 µM, and the structure-activity relationship among isolated compounds was discussed.

Ecological and pharmacognostical characteristics in Ephedra saxatilis in the Yarlung Zangbo River Valley of southeastern Tibetan Plateau, China.

In the Yarlung Zangbo River Valley of the southeastern Tibetan Plateau, China (29°07'49.5"N, 92°41'11.0"E, 3256 m above sea level), we found an Ephedra saxatilis community in the xeric steppe with shrubland vegetation habitat of the broad alluvial plain of the river with soil having relatively higher water-soluble cation (Ca2+, 8.62; K+, 1.94; Mg2+, 2.38 mmol/100 g dry soil weight) and nitrogen (NO3-, 21.78; NH4+, 1.82 mmol/100 g dry soil weight) content. The ranges of ephedrine and pseudoephedrine in 13 E. saxatilis samples were as follows: ephedrine, not detected-3.03 of dry weight (%DW) and pseudoephedrine, not detected-1.36%DW. The 13 E. saxatilis plants collected in the study area showed intraspecific variability of ephedrine and pseudoephedrine with 6 samples containing ephedrine and pseudoephedrine, 6 samples containing only ephedrine, and 1 sample containing only pseudoephedrine.

Successful treatment of immune-related cystitis by Chai-Ling-Tang (Sairei-To) in a gastric carcinoma patient: Case report and literature review.

BACKGROUND: Immune checkpoint inhibitors (ICIs) have changed the landscape of advanced cancer treatment. However, immune checkpoint inhibitors can trigger effector T cells against self-antigens as well as tumor antigens, resulting in immune-related toxicities in normal organs, referred to as immune-related adverse events (irAEs). CASE SUMMARY: A 56-year-old man with undifferentiated gastric carcinoma received sintilimab plus paclitaxel and tegafur therapy. After five cycles of treatment, the patient was referred to the hospital for sudden onset urinary frequency, micturition pain, and urinary incontinence. Cystoscopy revealed the entire bladder mucosa was red and edematous but there was no evidence of tumor. Oral administration of Chai-Ling-Tang (Sairei-To) alleviated lower urinary tract symptoms (LUTS). Histological analysis revealed numerous infiltrates of CD3-positive and CD8-positive cells into the urothelium but no atypia, indicating a diagnosis of immune-related cystitis. Interestingly, the urothelial epithelium infiltrated by lymphocytes and subepithelial inflammatory cells strongly expressed cell boundary PD-L1. The dose of Chai-Ling-Tang was maintained and stopped 2 months later without recurrence of LUTS. Since recovering from cystitis, the patient remains alive with no disease progression. CONCLUSION: This report shows that Chai-Ling-Tang is safe and effective for treating immune-related cystitis. The detailed mechanism of action requires further investigation.

New triterpenoids from the Cyclocarya paliurus (Batalin) Iljinskaja and their anti-fibrotic activity.

Cyclocarya paliurus, a Chinese herbal medicine and new food resource, contains a triterpenic-acid-rich extract that demonstrated ameliorative effect on diabetic nephropathy (DN). A more in-depth discovery of functional components led to the isolation of seven new triterpenoids including two pentacyclic triterpenes, 1α,2α,3ß,23-tetrahydroxyolean-12-en-28-oic acid and 2α,3ß,22α-tirhydroxyurs-12-en-28-oic acid 28-O-ß-D-glucopyranoside, and five tetracyclic triterpenoid glycosides (cypaliurusides N-R), together with twelve known compounds from the leaves of C. paliurus. Their structures were determined using a comprehensive analysis of chemical and spectroscopic data. Partial compounds were assessed for anti-fibrotic activities in high-glucose and TGF-ß1 induced HK-2 cells. Compound 16 remarkably decreased the level of fibronectin with an inhibition rate of 37.1%. Furthermore, 16 effectively alleviated the epithelial-mesenchymal transformation (EMT) process by upregulating E-cadherin expression and downregulating α-SMA expression, and it significantly decreased the level of the transcriptional inhibitors (Snail and Twist) of E-cadherin. The discovery of anti-fibrotic compounds from C. paliurus provides the potential utilization and functional candidates for the DN prevention.

Analysis of EBN Interventions in the Perioperative Period of Minimally Invasive Surgery for Intrahepatic and Extrahepatic Bile Duct Stones.

Context: Evidence-based nursing (EBN) is a model of care that emphasizes the formation of scientific findings, together with the development of individualized care plans that consider a patient's condition. Few studies have occurred on EBN interventions for patients with intrahepatic or extrahepatic bile duct stones who are in the perioperative period of minimally invasive surgery. Objective: The study intended to investigate the benefits of EBN interventions for patients with intrahepatic or extrahepatic bile duct stones who are in the perioperative period of minimally invasive surgery. Methods: The research team designed a prospective, randomized controlled trial. Setting: The study took place in the Department of Hepatobiliary Surgery at Wuhan No.1 Hospital in Wuhan, Hubei, China. Participants: Participants were 72 patients with intrahepatic or extrahepatic bile duct stones who had been admitted to the hospital between April 2019 and September 2021. Intervention: Participants were randomly assigned to one of two groups, an intervention group, which received an EBN intervention (n = 36), or a control group, which received conventional perioperative care (n = 36). Randomization occurred using a random number table. Outcome Measures: At baseline and postintervention, the study measured participants' early postoperative-recovery indicators, identified surgical complications, and assessed quality of life (QoL), using World Health Organization's (WHO's) Quality of Life-BREF (WHOQOL-BREF) scale, and psychological status, using the Hamilton depression (HAMD) and Hamilton anxiety (HAMA) scales. Results: In the intervention group, the mean values within 72 h after surgery for time to first gastric discharge after surgery, postoperative exhaust (P < .001); length of hospital stay (P = .0032), and pain score were significantly lower than those in the control group (P < .001). For QoL, the intervention group's score was significantly higher than that of control group in all domains (P < .05). The intervention group's depression (P < .001) and anxiety scores were significantly lower than those of the control group (P = .0001). In the intervention group, complications were all significantly lower than those in the control group (P < .05). Conclusion: For patients with intrahepatic or extrahepatic bile duct stones who are in the perioperative period for minimally invasive surgery, EBN interventions can improve their quality of life, improve their psychological statuses, reduce the occurrence of related complications, and facilitate their recovery.

Relationship between ephedrine alkaloid profile in Ephedra gerardiana and soil characteristics of glacial landforms in southeastern Tibetan Plateau, China.

In the Kaluxung River catchment of the southeastern Tibetan Plateau in China, we identified three Ephedra gerardiana communities on different soils and glacial landforms from 4842 to 4899 m above sea level: a moraine community located on constantly collapsing sandy gravel alpine steppe slopes with exposed bedrock on the outer slope of the terminal moraine of the Qiangyong Glacier on Mt. Kaluxung; an outwash plain community located on a gentle alpine steppe slope with exposed bedrock at the terminal end of the outwash plain in the glacial valley of the southeast side of Mt. Noijinkangsang; and a river terrace community located in an alpine meadow on a rock-scattered flat river terrace along a glacier-fed river in the outwash plain in the glacial valley of the southeast side of Mt. Noijinkangsang. Based on the finding of identical DNA sequences of the intergenic spacers of chloroplast trnT-trnF and trnS-trnfM regions for all Ephedra specimens examined in this study, the E. gerardiana in this study were considered to comprise a genetically homogeneous population. Analysis of the relationship between ephedrine alkaloid profiles of these three communities and soil characteristics showed that the river terrace community in wet alpine meadow had significantly lower ephedrine content than did the moraine and outwash plain communities in dry alpine steppe (moraine community, 1.52 ± 0.44; outwash plain community, 1.42 ± 0.68; river terrace community, 0.33 ± 0.65%DW), but pseudoephedrine content showed the reverse pattern (moraine community, 0.86 ± 0.30; outwash plain community, 0.73 ± 0.60; river terrace community, 1.50 ± 0.71%DW). In addition, total alkaloid (ephedrine and pseudoephedrine) content in the river terrace community (1.83 ± 0.24%DW) was significantly lower than that in the moraine community (2.38 ± 0.64%DW) and outwash plain community (2.15 ± 0.55%DW).

Dietary stevia residue extract supplementation improves the performance and antioxidative capacity of growing-finishing pigs.

BACKGROUND: Improper disposal of stevia residue causes environmental pollution and waste of resources. The extract of stevia residue is rich in chlorogenic acid and isochlorogenic acids, and has a great potential in livestock and poultry breeding. Therefore, this study aimed to investigate the effects of dietary stevia residue extract (SRE) supplementation on the performance, meat quality, antioxidative capacity and gut microbiota in growing-finishing pigs. RESULTS: The results showed that increasing the concentration of SRE supplementation linearly increased (P < 0.05) body weight from day 1 to 35. Supplementation with SRE significantly increased (P < 0.05) average daily gain (ADG) from day 1 to 75. 100 mg kg-1 SRE supplementation significantly increased (P < 0.05) hot carcass weight and gastric index. Moreover, increasing the concentration of SRE linearly increased (P < 0.05) the score of appearance of longissimus thoracis, as well as serum albumin, triglyceride and high-density lipoprotein cholesterol content. Further study found that increasing the concentration of SRE linearly increased (P < 0.05) serum total superoxide dismutase activity, and showed a significant quadratic relationship (P < 0.05) with activity of serum catalase, while linearly decreasing (P < 0.05) muscle malondialdehyde (MDA) content. Furthermore, supplementation with 100 mg kg-1 SRE significantly decreased (P < 0.05) serum MDA content, while 600 and 800 mg kg-1 SRE supplementation significantly decreased (P < 0.05) muscle MDA content. However, SRE supplementation had no significant effect on gut microbiota (P > 0.05). CONCLUSION: These data indicated that dietary SRE supplementation improves the performance and antioxidative capacity of growing-finishing pigs. We recommend that the optimal supplemental level of SRE in the diet of growing-finishing pigs is 100 mg kg-1 . © 2022 Society of Chemical Industry.

Rare cytochalasans isolated from the mangrove endophytic fungus Xylaria arbuscula.

Four new cytochalasans, arbuschalasins A-D (1-4), along with thirteen known analogues (5-17), were isolated from the solid rice medium of endophytic fungus Xylaria arbuscula. Arbuschalasins A-B feature a rare 5/6/6/6 fused ring system while arbuschalasin D was characterized as the first example of natural cytochalasans that possesses a 5/5/11 fused scaffold. The structures of 1-4 were assigned by spectroscopic data, with their absolute structures being determined by electronic circular dichroism (ECD) calculations. All of the isolates were evaluated against the human colorectal adenocarcinoma cell lines (HCT15). Compounds 6 and 7 showed significant inhibitory effects (IC50 values were 13.5 and 13.4 µM, respectively), being more active than those of the positive control, fluorouracil (103.1 µM).

Effects of MBSR therapy on negative emotions, fatigue, and sleep quality in "post-ICU patients": A randomized controlled clinical trial protocol.

BACKGROUND: Survivors of intensive care unit (ICU) transfer to the common ward are often accompanied by psychological distress, negative emotions, fatigue, and sleep disturbances that affect recovery. Mindfulness-based stress reduction (MBSR) has achieved reliable results in improving physical and mental health. However, no clinical study has been conducted to evaluate the effects of MBSR on negative emotions, fatigue and sleep quality of patients who survived ICU and were transferred to general wards. METHODS: This is a prospective randomized controlled trial (RCT) examining the effects of MBSR on negative emotions, fatigue, and sleep quality in inpatients transferred from ICU to general ward. Participants were randomly divided into the treatment group and the control group in a ratio of 1:1. On the basis of the same nursing plan and health education, the treatment group received MBSR therapy, while the control group received no other interventions, and all the patients were followed up for 3 months after 2 weeks of continuous treatment. The indicators included negative mood indicators [Self-rating Depression Scale (SDS) and Self-Rating Anxiety Scale (SAS)], fatigue index [Fatigue Severity Scale (FSS) and Brief Fatigue Inventory (BFI)], and sleep quality index [Pittsburgh Sleep Quality Index (PSQI)]. Finally, SPSS 20.0 software was used for statistical analysis of the data. DISCUSSION: This study will evaluate the effects of MBSR on negative emotions, fatigue, and sleep quality in hospitalized patients transferred from ICU to general ward. The results of this study will provide a reference for MBSR to improve psychological distress in ICU survivors transferred to general ward. TRIAL REGISTRATION: This study protocol was registered in the Open Science Framework (OSF) (registration number: DOI 10.17605/OSF.IO/PD7SU).

A novel homozygous SLC39A14 variant in an infant with hypermanganesemia and a review of the literature.

Background: Manganese (Mn) is an essential trace metal necessary for good health; however, excessive amounts in the body are neurotoxic. To date, three genes (SLC30A10, SLC39A8, and SLC39A14) have been discovered to cause inborn errors in Mn metabolism in humans. As very rare diseases, the clinical features require further clarification. Methods: A male Chinese patient who mainly presented with hypermanganesemia and progressive parkinsonism-dystonia was recruited for this study. We collected and analyzed clinical information, performed whole-exome sequencing (WES), and reviewed the relevant literature. Results: The motor-developmental milestones of the patient were delayed at the age of 4 months, followed by rapidly progressive dystonia. The patient displayed elevated Mn concentrations in blood and urine, and brain magnetic resonance imaging (MRI) showed symmetrical hyperintensity on T1-weighted images and hypointensity on T2-weighted images in multiple regions. A novel homozygous variant of the SLC39A14 gene (c.1058T > G, p.L353R) was identified. The patient was treated with disodium calcium edetate chelation (Na2CaEDTA). Three months later, mild improvement in clinical manifestation, blood Mn levels, and brain MRI was observed. To date, 15 patients from 10 families have been reported with homozygous mutations of SLC39A14, with a mean age of onset of 14.9 months. The common initial symptom is motor regression or developmental milestone delay, with a disease course for nearly all patients involving development of progressive generalized dystonia and loss of ambulation before treatment. Additionally, hypermanganesemia manifests as Mn values ranging from 4- to 25-fold higher than normal baseline levels, along with brain MRI results similar to those observed in the recruited patient. Nine SLC39A14 variants have been identified. Seven patients have been treated with Na2CaEDTA, and only one patient achieved obvious clinical improvement. Conclusion: We identified a novel SLC39A14 mutation related to autosomal recessive hypermanganesemia with dystonia-2, which is a very rare disease. Patients present motor regression or delay of developmental milestones and develop progressive generalized dystonia. Chelation therapy with Na2CaEDTA appears to effectively chelate Mn and increase urinary Mn excretion in some cases; however, clinical response varies. The outcome of the disease was unsatisfactory. This study expands the genetic spectrum of this disease.

Arjunolic acid from Cyclocarya paliurus ameliorates diabetic retinopathy through AMPK/mTOR/HO-1 regulated autophagy pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Cyclocarya paliurus (CP) is a traditional Chinese herb and possesses a variety of biological activities including anti-hyperglycemia, anti-hyperlipidemia, antioxidant and anti-inflammation. Arjunolic acid (AA) is an abundant and bioactive ingredient in CP that shows significant protection against many metabolic diseases such as diabetic complication. Diabetic retinopathy (DR) is a serious complication of diabetes and may lead to vision loss. However, the protective effects and underlying mechanisms of AA against DR is not still understood. AIM OF THE STUDY: We aimed to investigate whether AA activates AMPK/mTOR/HO-1 regulated autophagy pathway to alleviate DR. MATERIALS AND METHODS: In the study, the STZ-induced diabetic model of rats was established, and AA with 10 and 30 mg/kg dosages was given orally for ten weeks to investigate their effect on retinal injury of DR. H2O2-induced ARPE-19 cells were applied to evaluate anti-apoptosis and anti-oxidant effect of AA. RESULTS: The results revealed that AA could prevent STZ-induced weight loss and increase the retinal thickness and nuclei counts. The level of HO-1 protein was upregulated both in vivo and in vitro. In addition, AA prevented retinal damage and cell apoptosis through the AMPK-mTOR-regulated autophagy pathway. Furthermore, anti-apoptosis capacity, as well as the expression of HO-1 and LC3 protein, were effectively locked by AMPK inhibitor dorsomorphin dihydrochloride (compound C). CONCLUSIONS: This finding implies that AA may be a promising candidate drug by protecting retinal cells from STZ-induced oxidative stress and inflammation through the AMPK/mTOR/HO-1 regulated autophagy pathway.

Polyphyllin I Inhibits Propionibacterium acnes-Induced IL-8 Secretion in HaCaT Cells by Downregulating the CD36/NOX1/ROS/NLRP3/IL-1ß Pathway.

Acne vulgaris (AV) is a chronic skin disease involving inflammation of the pilosebaceous units. Propionibacterium acnes (P. acnes) hypercolonization is one pathogenic factor for AV. P. acnes that triggers interleukin-1ß (IL-1ß) by activating the pyrin domain-containing 3 protein (NLRP3) inflammasome of the NOD-like receptor family in human monocytes. Reactive oxygen species (ROS) acts as a trigger for the production of IL-8 and activates theNLRP3 inflammasome. IL-8 promotes the metastasis and multiplication of different cancerous cells, whereas keratinocyte proliferation and migration contribute to the progression of AV. A steroidal saponin called polyphyllin I (PPI) that is extracted from Paris polyphylla's rhizomes has anti-inflammatory properties. This study investigates the regulatory role of P. acnes in the secretion of IL-8 mediated by the CD36/NADPH oxidase 1 (NOX1)/ROS/NLRP3/IL-1ß pathway and the effects of PPI on the CD36/NOX1/ROS/NLRP3/IL-1ß/IL-8 pathway and human keratinocyte proliferation and migration. HaCaT cells were cultured and stimulated with 108 CFU/ml of P. acnes for 0, 6, 12, 18, 24, 30, and 36 hours. P. acnes induced IL-8 secretion from HaCaT cells via the CD36/NOX1/ROS/NLRP3/IL-1ß pathway. PPI inhibited the CD36/NLRP3/NOX1/ROS/IL-8/IL-1ß pathway and HaCaT cell proliferation and migration. PPI alleviates P. acnes-induced inflammatory responses and human keratinocyte proliferation and migration, implying a novel potential therapy for AV.

Four new dammarane triterpenoid glycosides from the leaves of Cyclocarya paliurus and their SIRT1 activation activities.

Four new C-11 monosaccharide attached dammarane triterpenoid glycosides cypaliurusides SV (1-4), along with nine known dammarane triterpenoid glycosides (5-13) were isolated from a CHCl3-soluble extract of the leaves of Cyclocarya paliurus. All characterized compounds were assayed for their cytotoxicities against HepG2 cells and 10 compounds were evaluated for the agonistic effects on sirtuin1 (SIRT1). The results showed that compounds 1, 5 and 6 were strongly cytotoxic in HepG2 cell line. Two dammarane triterpenoid glycosides 3 and 10 exhibited agonistic activities on SIRT1 with IC50 of 10 µM and 20 µM, respectively.

Utilization of preconception care and its impacts on health behavior changes among expectant couples in Shanghai, China.

BACKGROUND: Preconception care is an opportunity for detecting potential health risks in future parents and providing health behavior education to reduce morbidity and mortality for women and their offspring. Preconception care has been established in maternal and child health hospitals in Shanghai, China, which consists of health checkups, health education and counseling. This study investigated factors associated with the utilization of preconception care, and the role of preconception care on health behavior changes before conception among pregnant women and their partners. METHODS: A cross-sectional study was conducted among pregnant women at three maternal and child health hospitals in Shanghai. The participants were invited to complete a self-administered questionnaire on the utilization of preconception care and health behavioral changes before conception. RESULTS: Of the 948 recruited pregnant women, less than half (42.2%) reported that they had utilized preconception care before the current pregnancy. Unplanned pregnancy, unawareness of preconception care and already having a general physical examination were the main reasons for not attending preconception care. The two main sources of information about preconception care were local community workers and health professionals. Younger women and the multipara were less likely to utilize preconception care. Women who utilized preconception care were more likely to take folic acid supplements before conception [Adjusted Odds Ration (aOR) 3.27, 95% Confidence Interval (CI) 2.45-4.36, P < 0.0001]. The partners of pregnant women who had attended preconception care services were more likely to stop smoking [aOR 2.76, 95%CI 1.48-5.17, P = 0.002] and to stop drinking [aOR 2.13, 95%CI 1.03-4.39, P = 0.041] before conception. CONCLUSIONS: Utilization of preconception care was demonstrated to be positively associated with preconception health behavior changes such as women taking folic acid supplements before pregnancy, their male partner stopping smoking and drinking before conception. Future studies are needed to explore barriers to utilizing preconception care services and understand the quality of the services. Strategies of promoting preconception care to expectant couples, especially to young and multipara women, should be developed to further improve the utilization of the services at the community level.

Dietary Geranylgeranyl Pyrophosphate Counteracts the Benefits of Statin Therapy in Experimental Pulmonary Hypertension.

BACKGROUND: The mevalonate pathway generates endogenous cholesterol and intermediates including geranylgeranyl pyrophosphate (GGPP). By reducing GGPP production, statins exert pleiotropic or cholesterol-independent effects. The potential regulation of GGPP homeostasis through dietary intake and the interaction with concomitant statin therapy is unknown. METHODS: We developed a sensitive high-pressure liquid chromatography technique to quantify dietary GGPP and conducted proteomics, qualitative real-time polymerase chain reaction screening, and Western blot to determine signaling cascades, gene expression, protein-protein interaction, and protein membrane trafficking in wild-type and transgenic rats. RESULTS: GGPP contents were highly variable depending on food source that differentially regulated blood GGPP levels in rats. Diets containing intermediate and high GGPP reduced or abolished the effects of statins in rats with hypoxia- and monocrotaline-induced pulmonary hypertension: this was rescuable by methyl-allylthiosulfinate and methyl-allylthiosulfinate-rich garlic extracts. In human pulmonary artery smooth muscle cells treated with statins, hypoxia activated RhoA in an extracellular GGPP-dependent manner. Hypoxia-induced ROCK2 (Rho associated coiled-coil containing protein kinase 2)/Rab10 (Ras-related protein rab-10) signaling was prevented by statin and recovered by exogenous GGPP. The hypoxia-activated RhoA/ROCK2 pathway in rat and human pulmonary artery smooth muscle cells upregulated the expression of Ca2+-sensing receptor (CaSR) and HIMF (hypoxia-induced mitogenic factor), a mechanism attenuated by statin treatment and regained with exogenous GGPP. Rab10 knockdown almost abrogated hypoxia-promoted CaSR membrane trafficking, a process diminished by statin and resumed by exogenous GGPP. Hypoxia-induced pulmonary hypertension was reduced in rats with CaSR mutated at the binding motif of HIMF and the interaction between dietary GGPP and statin efficiency was abolished. In humans fed a high GGPP diet, blood GGPP levels were increased. This abolished statin-lowering effects on plasma GGPP, and also on hypoxia-enhanced RhoA activity of blood monocytes that was rescued by garlic extracts. CONCLUSIONS: There is important dietary regulation of GGPP levels that interferes with the effects of statin therapy in experimental pulmonary hypertension. These observations rely on a key and central role of RhoA-ROCK2 cascade activation and Rab10-faciliated CaSR membrane trafficking with subsequent overexpression and binding of HIMF to CaSR. These findings warrant clinical investigation for the treatment of pulmonary hypertension and perhaps other diseases by combining statin with garlic-derived methyl-allylthiosulfinate or garlic extracts and thus circumventing dietary GGPP variations.

Diallyl sulfide from garlic suppresses quorum-sensing systems of Pseudomonas aeruginosa and enhances biosynthesis of three B vitamins through its thioether group.

Diallyl sulfide (DAS) and diallyl disulfide (DADS), two constituents of garlic, can inhibit quorum sensing (QS) systems of Pseudomonas aeruginosa. However, the differences in the mechanism of QS inhibition between DAS and DADS, and the functional chemical groups of these sulfides that contribute in QS inhibition have not been elucidated yet. We assumed that the sulfide group might play a key role in QS inhibition. To prove this hypothesis and to clarify these unsolved problems, in this study, we synthesized diallyl ether (DAE), and compared and investigated the effects of DAS and DAE on the growth and production of virulence factors, including Pseudomonas quinolone signal (PQS), elastase and pyocyanin, of P. aeruginosa PAO1. Transcriptome analysis and qRT-PCR were used to compare and analyse the differentially expressed genes between the different treatment groups (DAS, DAE and control). The results indicated that DAS did not affect the growth dynamics of P. aeruginosa PAO1; however, DAS inhibited transcription of most of the QS system genes, including lasR, rhlI/rhlR and pqsABCDE/pqsR; thus, biosynthesis of the signal molecules C4 -HSL (encoded by rhlI) and PQS (encoded by pqsABCDE) was inhibited. Furthermore, DAS inhibited the transcription of virulence genes regulated by the QS systems, including rhlABC, lasA, lasB, lecA and phzAB, phzDEFG, phzM and phzS that encode for rhamnolipid, exoprotease, elastase, lectin and pyocyanin biosynthesis respectively. DAS also enhanced the expression of the key genes involved in the biosynthesis of three B vitamins: folate, thiamine and riboflavin. In conclusion, DAS suppressed the production of some virulence factors toxic to the host and enhanced the production of some nutrition factors beneficial to the host. These actions of DAS may be due to its thioether group. These findings would be significant for development of an effective drug to control the virulence and pathogenesis of the opportunistic pathogen P. aeruginosa.