The First Lanthipeptide from Lactobacillus iners, Inecin L, Exerts High Antimicrobial Activity against Human Vaginal Pathogens.

Vaginal infections continue to be a serious public health issue, and developing new approaches to address antibiotic-resistant pathogens is an urgent task. The dominant vaginal Lactobacillus species and their active metabolites (e.g., bacteriocins) have the potential to defeat pathogens and help individuals recover from disorders. Here, we describe for the first time a novel lanthipeptide, inecin L, a bacteriocin from Lactobacillus iners with posttranslational modifications. The biosynthetic genes of inecin L were actively transcribed in the vaginal environment. Inecin L was active against the prevailing vaginal pathogens, such as Gardnerella vaginalis and Streptococcus agalactiae, at nanomolar concentrations. We demonstrated that the antibacterial activity of inecin L was closely related to the N terminus and the positively charged His13 residue. In addition, inecin L was a bactericidal lanthipeptide that showed little effect on the cytoplasmic membrane but inhibited the cell wall biosynthesis. Thus, the present work characterizes a new antimicrobial lanthipeptide from a predominant species of the human vaginal microbiota. IMPORTANCE The human vaginal microbiota plays essential roles in preventing pathogenic bacteria, fungi, and viruses from invading. The dominant vaginal Lactobacillus species show great potential to be developed as probiotics. However, the molecular mechanisms (such as bioactive molecules and their modes of action) involved in the probiotic properties remain to be determined. Our work describes the first lanthipeptide molecule from the dominant Lactobacillus iners. Additionally, inecin L is the only lanthipeptide found among the vaginal lactobacilli thus far. Inecin L shows strong antimicrobial activity toward the prevalent vaginal pathogens and antibiotic-resistant strains, suggesting that inecin L is a potent antibacterial molecule for drug development. In addition, our results show that inecin L exhibits specific antibacterial activity related to the residues in the N-terminal region and ring A, which will contribute to structure-activity relationship studies in lacticin 481-like lanthipeptides.

Organocatalytic Asymmetric Morita-Baylis-Hillman Reaction of Isatins with Vinyl Sulfones.

The organocatalytic asymmetric Morita-Baylis-Hillman (MBH) reaction of isatin derivatives with various vinyl sulfones is disclosed. Chiral sulfone-containing 3-hydroxyoxindoles were produced in good to high yields and with good to high ee's. This report displays an unprecedented example to apply activated alkenes with sulfone moiety other than carbonyl groups in asymmetric MBH reactions and provides an efficient strategy to incorporate the sulfone functional group for the synthesis of chiral 3-hydroxyoxindoles.

In Situ Observations of Halogenated Gases at the Shangdianzi Background Station and Emission Estimates for Northern China.

Halogenated gases include ozone-depleting substances and greenhouse gases, such as chlorofluorocarbons, halons, hydrochlorofluorocarbons, hydrofluorocarbons, and perfluorinated gases. In situ atmospheric observations of major halogenated gases were conducted at the Shangdianzi (SDZ) background station, China, from October 2020 to September 2021 using ODS5-pro, a newly developed measurement system. The measurement time series of 36 halogenated gases showed occasional pollution events, where background conditions represented 25% (CH2Cl2) to 81% (CF3Cl, CFC-13) of the measurements. The annual mean background mole fractions of most species at SDZ were consistent with those obtained at the Mace Head station in Ireland. The background conditions were distinguished from pollution events, and the enhanced mole fractions were used to estimate the emissions of four categories of fluorinated gases (F-gases) from northern China using a tracer ratio method. The CO2-equivalent (CO2-equiv) emission of F-gases from northern China reached 181 ± 18 Tg year-1 during 2020-2021. Among the four categories of F-gases estimated, SF6 accounted for the highest proportion of CO2-equiv emissions (24%), followed by HFC-23 (22%), HFC-125 (17%), HFC-134a (13%), NF3 (10%), CF4 (5.9%), HFC-143a (3.9%), HFC-32 (3.4%), and HFC-152a (0.2%).

[Application of metagenomic next-generation sequencing of bronchoalveolar lavage fluid in the diagnosis and treatment of refractory pneumonia in children]. / æ”¯æ°”ç®¡è‚ºæ³¡çŒæ´—æ¶²å®åŸºå› ç»„äºŒä»£æµ‹åºåœ¨å„¿ç«¥éš¾æ²»æ€§è‚ºç‚Žè¯Šæ²»ä¸­çš„åº”ç”¨.

OBJECTIVES: To investigate the clinical application of metagenomic next-generation sequencing (mNGS) of bronchoalveolar lavage fluid (BALF) in the etiological diagnosis and treatment of refractory pneumonia (RTP) in children. METHODS: A retrospective analysis was performed on 160 children with RTP who were admitted to the Department of Pediatric Internal Medicine, Maternal and Child Health Hospital of Inner Mongolia Autonomous Region, from January 2020 to March 2023. According to whether mNGS was performed, they were divided into two groups: mNGS (n=80) and traditional testing (n=80). All children received the tests of inflammatory markers and pathogen tests after admission. Traditional pathogenicity tests included microbial culture (sputum specimen collected by suction tube), nucleic acid detection of respiratory pathogens, and serological test (mycoplasma, tuberculosis, and fungi). For the mNGS group, BALF specimens were collected after bronchoscopy and were sent to the laboratory for mNGS and microbial culture. The two groups were analyzed and compared in terms of the detection of pathogens and treatment. RESULTS: Compared with the traditional testing group, the mNGS group had a significantly higher detection rate of pathogens (92% vs 58%, P<0.05), with more types of pathogens and a higher diagnostic rate of mixed infections. Compared with the traditional testing group, the mNGS group had a significantly higher treatment response rate and a significantly lower incidence rate of complications during hospitalization (P<0.05). Treatment was adjusted for 68 children in the mNGS group according to the results of mNGS, with a treatment response rate of 96% (65/68) after adjustment. CONCLUSIONS: Compared with traditional pathogen tests, BALF mNGS can significantly improve the detection rate of pathogens and find some rare pathogens. In clinical practice, when encountering bottlenecks during the diagnosis and treatment of children with RTP, it is advisable to promptly perform the mNGS to identify the pathogens.

A Peptide Derived from GAPDH Enhances Resistance to DNA Damage in Saccharomyces cerevisiae Cells.

Social behaviors do not exist only in higher organisms but are also present in microbes that interact for the common good. Here, we report that budding yeast cells interact with their neighboring cells after exposure to DNA damage. Yeast cells irradiated with DNA-damaging UV light secrete signal peptides that can increase the survival of yeast cells exposed to DNA-damaging stress. The secreted peptide is derived from glyceraldehyde-3-phosphate dehydrogenase (GAPDH), and it induced cell death of a fraction of yeast cells in the group. The data suggest that the GAPDH-derived peptide serves in budding yeast's social interaction in response to DNA-damaging stress. IMPORTANCE Many studies have shown that microorganisms, including bacteria and yeast, display increased tolerance to stress after exposure to the same stressor. However, the mechanism remains unknown. In this study, we report a striking finding that Saccharomyces cerevisiae cells respond to DNA damage by secreting a peptide that facilitates resistance to DNA-damaging stress. Although it has been shown that GAPDH possesses many key functions in cells aside from its well-established role in glycolysis, this study demonstrated that GAPDH is also involved in the social behaviors response to DNA-damaging stress. The study opens the gate to an interesting research field about microbial social activity for adaptation to a harsh environment.

Association between 5-hydroxytryptamine gene polymorphism rs140700 and primary insomnia in Chinese population.

BACKGROUND: Primary insomnia is a worldwide problem and it has a considerable negative impact on one's physical and mental health. Studies have shown that non-synonymous Single-nucleotide polymorphisms in 5-hydroxytryptamine (serotonin or 5-HT) are related to primary insomnia. Previous studies have shown that 5-HT polymorphism (rs140700) is related to depression, and insomnia is often accompanied by depression and anxiety. The relationship between this site and primary insomnia is unknown. We speculated that this site may be related to primary insomnia, so we investigated the relationship between rs140700 and primary insomnia. AIMS: To explore the relationship between the 5-HT gene polymorphism rs140700 and primary insomnia. METHODS: In this study, we included 57 patients with primary insomnia and 54 age- and gender-matched normal controls. The subjects who belonged to the Chinese population were subjected to polysomnography for three consecutive nights. Their sleep quality was assessed, and the genotypes of the 5-hydroxytryptamine (5-HT) gene polymorphism rs140700 were determined by the flight mass spectrometry. RESULTS: The genotype distributions of the 5-HT gene polymorphism rs140700 were in Hardy-Weinberg equilibrium in both patients and controls (P > 0.05). The allele and genotype distributions of this variant were comparable between the patients and controls in all subjects and between genders (all P > 0.05). The influence of rs140700 on percentage of stage 1 (P = 0.015) change and arousal index (P = 0.028) of primary insomnia was statistically significant. The logistic multi-factor regression analysis results revealed that 5-HT gene polymorphism rs140700 was not a risk factor for primary insomnia in the Chinese population (P = 0.589). CONCLUSIONS: The 5-HT gene polymorphism rs140700 may not be a susceptibility locus for primary insomnia in the Chinese population.

Tropospheric NO2 vertical column densities retrieved from ground-based MAX-DOAS measurements at Shangdianzi regional atmospheric background station in China.

Ground-basedMulti-AXis Differential Optical Absorption Spectroscopy (MAX-DOAS) measurements were performed at Shangdianzi (SDZ) regional atmospheric background station in northern China from March 2009 to February 2011. The tropospheric NO2 vertical column densities (VCDs) were retrieved to investigate the background condition of the Beijing-Tianjin-Hebei developed economic circle in China. The seasonal variation of mean NO2 tropospheric VCDs (VCDTrop) at SDZ is apparent, with the maximum (1.3 × 1016 molec/cm2) in February and the minimum (3.5 × 1015 molec/cm2) in August, much lower than those observed at the Beijing city center. The average daytime diurnal variations of NO2 VCDTrop are rather consistent for all four seasons, presenting the minimum at noon and the higher values in the morning and evening. The largest and lowest amplitudes of NO2 VCDTrop diurnal variation appear in winter and in summer, respectively. The diurnal pattern at SDZ station is similar to those at other less polluted stations, but distinct from the ones at the urban or polluted stations. Tropospheric NO2 VCDs at SDZ are strongly dependent on the wind, with the higher values being associated with the pollution plumes from Beijing city. Tropospheric NO2 VCDs derived from ground-based MAX-DOAS at SDZ show to be well correlated with corresponding OMI (Ozone Monitoring Instrument) satellite products with a correlation coefficient R = 0.88. However, the OMI observations are on average higher than MAX-DOAS NO2 VCDs by a factor of 28%, probably due to the OMI grid cell partly covering the south of SDZ which is influenced more by the pollution plumes from the urban areas.

Diastereoselective Total Synthesis of (±)-Basiliolide B and (±)-epi-8-Basiliolide B.

The C8 and C9 stereogenic centers of the basiliolide/transtaganolide family have been established stereoselectively using a cyclopropane ring-opening strategy, which has been studied by DFT calculations of a variety of lithium-chelating models. The highly functionalized intermediates obtained in this strategy were successfully employed for the diastereoselective total synthesis of (±)-basiliolide B and (±)-epi-8-basiliolide B. The decalin core with a lactone bridge was constructed via a 2-pyrone Diels-Alder (DA) cycloaddition, and the unprecedented seven-membered acyl ketene acetal was established by a biomimetic intramolecular O-acylation cyclization.

Effect of Resorbable Collagen Plug on Bone Regeneration in Rat Critical-Size Defect Model.

OBJECTIVE: The purpose of this investigation was to examine the effect of resorbable collagen plug (RCP) on bone regeneration in rat calvarial critical-size defects. METHODS: About 5-mm-diameter calvarial defects were created in forty 12-week-old male Sprague-Dawley rats and implanted with or without RCP. Animals were killed at 1, 2, 4, and 8 weeks postoperatively. After being killed, specimens were collected and subjected to micro-computed tomography (µCT) and histological analysis. RESULTS: The µCT showed a significant increase of newly formed bone volume/tissue volume in RCP-implanted defect compared with controls at all designated time points. After 8 weeks, the defects implanted with RCP displayed almost complete closure. Hematoxylin and eosin staining of the decalcified sections confirmed these observations and evidenced active bone regeneration in the RCP group. In addition, Masson's trichrome staining demonstrated that RCP implantation accelerated the process of collagen maturation. CONCLUSIONS: The RCP enhances bone regeneration in rat critical-size cranial defects, which suggest it might be a desired material for bone defect repair.

Solvothermal Synthesis of Indium Telluride Nanowires and Its Photoelectrical Property.

In this paper, 1D In2Te3 nanowires were synthesizes through a simple solvothermal approach. The morphology was first studied by scanning electron microscopy (SEM) and Transmission electron microscopy (TEM). From the results, the nanowires have a diameter from 100 to 200 nm and a length of dozens of microns. X-ray Diffraction (XRD), X-ray photoelectron spectroscopy (XPS) and Raman spectrum were used to study the composition, crystal structures, and optical property. Based on the typical nanowire sample, experiment factors were changed to synthsize other samples in order to study the influence factors. A possible growth mechanism of the nanowires was proposed based on a series of experimental results. This material has a broad light detection range covering the UV-visible-NIR region from the photoelectrical test, which makes it potential for applications in photodetectors and solar cells.

RIP3 overexpression sensitizes human breast cancer cells to parthenolide in vitro via intracellular ROS accumulation.

AIM: Receptor-interacting protein 3 (RIP3) is involved in tumor necrosis factor receptor signaling, and results in NF-κB-mediated prosurvival signaling and programmed cell death. The aim of this study was to determine whether overexpression of the RIP3 gene could sensitize human breast cancer cells to parthenolide in vitro. METHODS: The expression of RIP3 mRNA in human breast cancer cell lines (MCF-7, MDA-MB-231, MDA-MB-435 and T47D) was detected using RT-PCR. Both MDA-MB-231 and MCF-7 cells were transfected with RIP3 expression or blank vectors via lentivirus. Cell viability was measured with MTT assay; intracellular ROS level and cell apoptosis were analyzed using flow cytometry. RESULTS: RIP3 mRNA expression was not detected in the four human breast cancer cell lines tested. However, the transfection induced higher levels of RIP3 protein in MCF-7 and MDA-MB-231 cells. Furthermore, overexpression of RIP3 decreased the IC50 values of parthenolide from 17.6 to 12.6 µmol/L in MCF-7 cells, and from 16.6 to 9.9 µmol/L in MDA-MB-231 cells. Moreover, overexpression of RIP3 significantly increased parthenolide-induced apoptosis and ROS accumulation in MCF-7 and MDA-MB-231 cells. Pretreatment with N-acetyl-cysteine abrogated the increased sensitivity of RIP3-transfected MCF-7 and MDA-MB-231 cells to parthenolide. CONCLUSION: Overexpression of RIP3 sensitizes MCF-7 and MDA-MB-231 breast cancer cells to parthenolide in vitro via intracellular ROS accumulation.

AGEs induce MMP-9 promoter demethylation through the GADD45α-mediated BER pathway to promote breast cancer metastasis in patients with diabetes.

Scientific evidence has linked diabetes to a higher incidence and increased aggressiveness of breast cancer; however, mechanistic studies of the numerous regulators involved in this process are insufficiently thorough. Advanced glycation end products (AGEs) play an important role in the chronic complications of diabetes, but the mechanisms of AGEs in breast cancer are largely unexplored. In this study, we first demonstrate that high AGEs levels in breast cancer tissues are associated with the diabetic state and poor patient outcomes. Furthermore, AGEs interact with the receptor for AGEs (RAGE) to promote breast cancer cell migration and invasion. Mechanistically, based on RNA sequencing (RNA-seq) analysis, we reveal that growth arrest and DNA damage gene 45α (GADD45α) is a vital protein upregulated by AGEs through a P53-dependent pathway. Next, GADD45α recruits thymine DNA glycosylase (TDG) for base excision repair to form the demethylation complex at the promoter region of MMP-9 and enhance MMP-9 transactivation through DNA demethylation. Overall, our results indicate a critical regulatory role of AGEs in patients with breast cancer and diabetes and reveal a novel mechanism of epigenetic modification in promoting breast cancer metastasis.

Effect of acupotomy combined with electroacupuncture on knee function of patients with knee osteoarthritis. / åˆƒé’ˆç»“åˆç”µé’ˆæ²»ç–—å¯¹è†å ³èŠ‚éª¨å ³èŠ‚ç‚Žæ‚£è€ è†å ³èŠ‚åŠŸèƒ½çš„å½±å“.

OBJECTIVES: To compare the clinical effect of combined therapy of acupotomy and electroacupuncture (EA) with the simple application of EA on knee osteoarthritis (KOA), and their influence on knee function. METHODS: Sixty-eight KOA patients were randomly divided into 2 groups, an acupotomy group and an EA group. In the acupotomy group, the combined therapy of acupotomy and EA was adopted. In the EA group, EA was simply used, delivered once every two days, 3 treatments a week；and the duration of treatment was 4 weeks. In the acupotomy group, besides the treatment as the EA group, acupotomy was combined once weekly, and the duration of treatment was 4 weeks. Separately, before and after treatment, and in 4 and 12 weeks after treatment completion (1-month and 3-month follow-up), the results of the timed up and go test (TUG), the 9-step stair climb test (9-SCT) and the knee function (Western Ontario and McMaster University osteoarthritis index visualization scale ［WOMAC］) were measured in the two groups. RESULTS: By the intention-to-treat analysis, the results of TUG, 9-SCT and WOMAC scores were reduced after treatment and in 1-month and 3-month follow-up when compared with those before treatment in the patients of the two groups (P<0.05). Compared with the EA group at the same time point, TUG results were decreased after treatment and in 1-month follow-up, and WOMAC score was reduced after treatment in the acupotomy group. WOMAC score in 1-month follow-up was reduced when compared with that before treatment within the acupotomy group (P<0.05). CONCLUSIONS: Either the simple application of EA or the combined therapy of acupotomy and EA can improve knee function, but the combined therapy obviously increases the walking speed and relieves the symptoms such as joint pain and morning stiffness. The treatment with acupotomy and EA is safe and effective on KOA and the long-term effect is satisfactory.

Asymmetric total synthesis of caribenol A via an intramolecular Diels-Alder reaction.

A total synthesis of the caribenol A (1), a novel natural product with an intriguing tetracyclic framework, has been achieved. The synthesis features an intramolecular Diels-Alder (IMDA) reaction for the facile construction of the tricyclic [5-7-6] skeleton of caribenol A (1) and a biomimetic oxidation reaction for the formation of the 2-hydroxyfuran-2(5H)-one motif of caribenol A (1) as key steps. This synthetic approach also reveals that the sp(2) carbon at C(2) in substrate 8 is a critical factor for the formation of the tricyclic [5-7-6] skeleton in 7.

[Effect of jianpihuashi decoction on rats with hyperuricemia].

OBJECTIVE: To investigate the effect of Jianpihuashi Decoction on rats with hyperuricemia. METHODS: Forty male Sprague-Dawley (SD) rats were randomly divided into four groups: normal, hyperuricemia, Jianpihuashi Decoction and Allopurinol group. After the administration for 0 day, 10 days, 20 days and 30 days, the serum uric acid, creatinine, urea nitrogen and xanthine oxidase (XOD) activity levels were separately detected using the orbital blood. 30 days after the experiment, the rats were anaesthetized by 3% pentobarbital sodium, liver tissue homogenate extracts were used to detect the XOD activity, and histopathological changes in kidney were observed by HE staining. RESULTS: Treatment with Jianpihuashi Decoction for 30 days, the serum uric acid level of rats with hyperuricemia were significantly decreased (P < 0.05). Simultaneously, the XOD activity in the serum and liver tissue homogenate extracts were obviously decreased by the decoction, which had seldom toxic or side effects on kidney. Allopurinol group could significantly decrease the serum uric acid level, but it had seldom pathological injury to kidney at the same time. CONCLUSION: Jianpihuashi Decoction which has seldom pathological injury to kidney can significantly decrease the effect of uric acid by suppressing XOD activity.

Bioinformatics analysis of human kallikrein 5 (KLK5) expression in metaplastic triple-negative breast cancer.

Background: Metaplastic breast carcinoma (MBC) is a rare breast cancer subtype; most cases are triple-negative breast cancers (TNBCs) and are poorly responsive to conventional systemic therapy. Few potential diagnostic and prognostic markers for distinguishing between metaplastic TNBC and nonmetaplastic TNBC have been discovered. We performed bioinformatic analysis to explore the underlying mechanism by which metaplastic TNBC differs from nonmetaplastic TNBC and provides potential pathogenic genes of metaplastic TNBC. Methods: Differentially expressed genes (DEGs) in metaplastic tumors and nonmetaplastic tumors from TNBC patients were screened using GSE165407. The GSE76275 data set and The Cancer Genome Atlas (TCGA) database were used to screen DEGs in TNBC and non-TNBC. Metascape and DAVID were used for the Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis and Gene Ontology (GO) analysis of DEGs. Online databases, including UALCAN, GEPIA, HPA, Breast Cancer Gene-Expression Miner, and quantitative PCR and western blot, were used to examine KLK5 messenger RNA and protein expression in breast cancer. Analysis of KLK5­associated genes was performed with TCGA data, and the LinkedOmics database was used to detect the genes co-expressed with KLK5. STRING (Search Tool for the Retrieval of Interacting Genes) and Cytoscape were used to screen for hub genes. Kaplan­Meier plotter was used for survival analysis. Results: KLK5 was identified among the DEGs in nonmetaplastic TNBC and metaplastic TNBC. The KLK5 gene was overexpressed in nonmetaplastic TNBC but downregulated in metaplastic TNBC. KEGG and GO analyses revealed that epithelial-to-mesenchymal transition was a pathogenic mechanism in metaplastic TNBC and an important pathway by which KLK5 and its associated genes DSG1 and DSG3 influence metaplastic TNBC progression. Prognosis analysis showed that only low expression of KLK5 in metaplastic TNBC had clinical significance. Conclusion: Our research indicated that KLK5 may be a pivotal molecule with a key role in the mechanism of tumorigenesis in metaplastic TNBC.

Palmitic acid induces nDNA release to cytosol and promotes microglial M1 polarization via cGAS-STING signaling pathway.

Palmitic acid (PA), the most common statured fatty acid in diets, is involved in peripheral as well as central inflammation. The M1 polarization of microglia plays an important role in PA-induced neuroinflammation. However, it is still unclear on the key factor and molecule mechanism of microglial polarization among it. Thus, we investigated whether the release of self-DNA into the cytoplasm of microglia was a consequence of PA treatment, as in aortic endothelial cells and adipocytes. RT-qPCR and immunofluorescence were performed to detect the status of cytosolic DNA and microglial polarization after PA treatment. We found that the content of cytosolic nDNA rather than mtDNA increased after PA treatment and the M1 polarization of microglia was associated with this. Moreover, the knockdown of cGAS in BV2 microglial cells demonstrated that the cGAS-STING pathway is involved in polarization process. Our results revealed that nDNA and cGAS-STING pathway are critically involved in PA-induced microglial M1 polarization. This mechanism may pose a new insight on targeting microglia may be a promising way to mitigate diet-induced early neuroinflammation.

Eisenmenger syndrome: not always inoperable.

Recently, advanced therapies for pulmonary arterial hypertension have become available, and have been effective in reducing pulmonary vascular resistance and symptoms in patients with Eisenmenger syndrome, previously thought to be inoperable. This review summarizes the current knowledge on the pathophysiology and treatment of Eisenmenger syndrome. The recent introduction of targeted therapies in pulmonary arterial hypertension has led to a renewed insight in the pathophysiology and treatment of Eisenmenger syndrome. Patients with Eisenmenger syndrome using a diagnostic-treatment-and-repair strategy are amenable to surgery after successful treatment with advanced therapy. With continued improvements in the diagnosis, preoperative management, refinement of surgical techniques and intra- and postoperative management strategies, the patients with Eisenmenger syndrome selected using a diagnostic-treatment-and-repair strategy are operable with safety and efficacy in the current era with advanced pulmonary arterial hypertension therapy. Future directions of Eisenmenger syndrome may be the combination of reversal of pulmonary vascular remodeling and correction.

Inhibition of 11b-HSD1 by tetracyclic triterpenoids from Euphorbia kansui.

The roots of Euphorbia kansui are considered an important traditional folk medicine. In this study the ethanol extracts of E. kansui were investigated. A new tetracyclic triterpenoid, euphane-3b,20-dihydroxy-24-ene, in addition to five known triterpenoids with euphane skeletons were isolated. Their structures were elucidated on the basis of physical and spectral techniques (1D-, 2D-NMR and MS, respectively). Furthermore, these compounds 1-6 exhibited strong inhibitory activity against human 11b-hydroxysteroid dehydrogenase type 1 (11b-HSD1), with IC(50) values of 34.86 nM, 1.115 mM, 16.08 nM, 2.815 nM, 26.47 nM, 15.99 nM, and 41.86 nM, respectively. The docking results show that the ring part of compounds can insert into the hydrophobic core of h11b-HSD1 and the alkane chain orientates toward the outside. The results presented herein provide a scientific explanation for the usage of the E. kansui in clinical treatment of diabetes.

L-Borneol 7-O-[ß-D-Apiofuranosyl-(1→6)]-ß-D-Glucopyranoside Alleviates Myocardial Ischemia-Reperfusion Injury in Rats and Hypoxic/Reoxygenated Injured Myocardial Cells via Regulating the PI3K/AKT/mTOR Signaling Pathway.

Ischemia/reperfusion (I/R) is a primary cause of morbidity and mortality in acute myocardial infarction (AMI). L-Borneol 7-O-[ß-D-apiofuranosyl-(1→6)]-ß-D-glucopyranoside (LBAG), extracted from the Radix Ophiopogonis, is the main bioactive component that may be exerting cardiovascular protection in AMI. The purpose was to examine the effects of LBAG on myocardial I/R injury (MIRI) in rats and H9c2 cells treated with hypoxia/reoxygenation (H/R). MIRI was induced through the combination of ischemia with reperfusion for 30 min and 24 h, respectively. LBAG was administered 7 days before vascular ligation. Myocardial function was detected by an electrocardiograph, histological, TTC, and TUNEL staining analyses. The influences of LBAG on the content concentration of cardiac enzymes in the serum were measured by ELISA. Moreover, H9c2 cells were exposed to LBAG or combined with AKT inhibitor (perifosine) and then exposed to H/R for simulating the cardiac injury process. Afterward, cell viability, LDH, CD-KM release, apoptosis, and autophagy were evaluated by CCK-8 and ELISA assays, flow cytometry, TUNEL, and immunofluorescence staining, respectively. Additionally, the proteins of apoptosis, autophagy, and PI3K/mTOR pathway were determined by western blotting. In I/R rats, LBAG pretreatment significantly ameliorated cardiac function, as illustrated by reducing the infarct size, myocardial autophagy, and apoptosis levels. In H/R-induced H9c2 cells, LBAG pretreatment significantly decreased cell apoptosis, LC3 II/I, and Beclin 1 levels, elevated the Bcl-2 levels, attenuated LDH, and CD-KM production. Moreover, LBAG pretreatment markedly increased the PI3K/mTOR pathway activation, and the protective influences of LBAG were partly abolished with the AKT inhibitor perifosine treatment. These findings demonstrated the protective functions of LBAG on I/R by regulating apoptosis and autophagy in vitro and in vivo by activating the PI3K/mTOR pathway.