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1.
Anal Chem ; 2020 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-32066230

RESUMO

Six mitochondria/lysosomes self-targetable and viscosity-sensitive dyes (1a-1f) were developed via simple structure modification on cyanine-derived dyes. They all showed remarkable OFF-ON fluorescent response to viscosity in the near-infrared region (652-690 nm) and exhibited good linear relationship with solution viscosity. The transient absorption spectra were used to evaluate the excited-state lifetime of dye 1a in different viscosity environments. Furthermore, cellular imaging assays indicated that different derivatives (1a-1f) with the same chromophore core exhibited different organelle-targeting abilities. Among them, dyes 1a-1c could sense lysosomal viscosity fluctuations while dyes 1d-1f could be applied in mitochondrial viscosity detections.

2.
J Diabetes Complications ; : 107558, 2020 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-32075751

RESUMO

AIMS: We aimed to evaluate the associations of mineralocorticoids with type 2 diabetes mellitus (T2DM) and glucose homeostasis among rural Chinese adults. METHODS: A total of 2713 participants were selected from the Henan Rural Cohort study. Serum mineralocorticoids were measured by liquid chromatography-tandem mass spectrometry. Logistic regression and restricted cubic splines were employed to evaluate the associations of mineralocorticoids with pre-diabetes and T2DM. Linear regression was implemented to assess the associations of aldosterone and 11-deoxycorticosterone with different markers of glucose homeostasis by different diabetes status. RESULTS: Elevated aldosterone and 11-deoxycorticosterone were associated with an increased prevalence of pre-diabetes and T2DM (P < 0.05), with a nonlinear dose-response trend, but the association between 11-deoxycorticosterone and T2DM was no statistical significance after adjustment. A 100% increase in ln-aldosterone was associated with a 0.029 mg/dl higher fasting plasma glucose (FPG) and a 1.2% higher HOMA2-IR among those with normal glucose tolerance (NGT), and related to a 0.034 mg/dl lower FPG, a 1.1% higher HbA1c and a 1.3% higher HOMA2-ß among individuals with pre-diabetes. A 100% increment in ln-11-deoxycorticosterone was associated with a 16% increase in HbA1c and a 5.6% decrease in HOMA2-ß in participants with T2DM. CONCLUSIONS: Higher aldosterone and 11-deoxycorticosterone are associated with T2DM risk and glucose homeostasis disorder among different diabetes status.

3.
Asian J Androl ; 2020 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-31929196

RESUMO

Surgical repair of complex posterior urethral disruptions remains one of the most challenging problems in urology. The efficacy of using a tissue expander capsule as an induced vascular bed to prefabricate axial vascularized buccal mucosa-lined flaps for tubularized posterior urethral reconstruction in a rabbit model was tested. The experiments were performed in three stages. First, silicone tissue expanders were inserted into the groin to induce vascularized capsule pouch formation. Next, buccal mucosa grafts were transplanted into the newly formed capsular tissue supplied by axial vessels for buccal mucosa-lined flap prefabrication. Then, circumferential posterior urethral defects were created and repaired with the buccal mucosa graft (Group 1), the capsule flap (Group 2), and the prefabricated capsule buccal mucosa composite flap (Group 3). After surgery, notable contracture of the tubularized buccal mucosa graft was observed in the neourethra, and none of the rabbits in Group 1 maintained a wide urethral caliber. In Group 2, the retrieved neourethra showed little evidence of epithelial lining during the study period, and the lumen caliber was narrowed at the 3-month evaluation. In Group 3, the buccal mucosa formed the lining in the neourethra and maintained a wide urethral caliber for 3 months. The capsule may serve as an induced vascular bed for buccal mucosa-lined flap prefabrication. The prefabricated buccal mucosa-lined flap may serve as a neourethra flap for posterior urethral replacement.

4.
BMC Genomics ; 21(1): 15, 2020 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-31906862

RESUMO

BACKGROUND: Cotton grows in altering environments that are often unfavorable or stressful for its growth and development. Consequently, the plant must cope with abiotic stresses such as soil salinity, drought, and excessive temperatures. Alkali-salt stress response remains a cumbersome biological process and is regulated via a multifaceted transcriptional regulatory network in cotton. RESULTS: To discover the molecular mechanisms of alkali-salt stress response in cotton, a comprehensive transcriptome analysis was carried out after alkali-salt stress treatment in three accessions of Gossypium hirsutum with contrasting phenotype. Expression level analysis proved that alkali-salt stress response presented significant stage-specific and tissue-specific. GO enrichment analysis typically suggested that signal transduction process involved in salt-alkali stress response at SS3 and SS12 stages in leaf; carbohydrate metabolic process and oxidation-reduction process involved in SS48 stages in leaf; the oxidation-reduction process involved at all three phases in the root. The Co-expression analysis suggested a potential GhSOS3/GhCBL10-SOS2 network was involved in salt-alkali stress response. Furthermore, Salt-alkali sensitivity was increased in GhSOS3 and GhCBL10 Virus-induced Gene Silencing (VIGS) plants. CONCLUSION: The findings may facilitate to elucidate the underlying mechanisms of alkali-salt stress response and provide an available resource to scrutinize the role of candidate genes and signaling pathway governing alkali-salt stress response.

5.
Talanta ; 209: 120580, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31892055

RESUMO

In this study, a mitochondria-specific fluorescent probe for efficient ratiometric detection of Cys was designed and investigated. Probe 1 is composed of a xanthylene skeleton and a benzyl group containing an acryloyl moiety. The probe showed excellent water solubility, good selectivity and sensitivity toward Cys over other analytes, and afforded an extremely low detection limit of 33.7 nM. The possible detection mechanism was ascertained by HRMS analysis. Moreover, probe 1 had excellent mitochondrial-targeting ability (the Pearson's correlation coefficient was 0.96), and was capable of monitoring endogenous Cys in living HeLa cells by dual channel ratiometric bioimaging, demonstrating its significant potential in biological applications.

6.
J Clin Endocrinol Metab ; 105(3)2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31912872

RESUMO

PURPOSE: The aims of this study were to evaluate the effect of age at menarche (AM) on type 2 diabetes mellitus (T2DM) and to assess whether the fasting plasma glucose (FPG) and homeostasis model assessment (HOMA) index responses to AM and menopause status interact in Chinese rural adults. METHODS: A cross-sectional, population-based study including 23 138 participants was performed. Logistic regression and multivariable linear regression were performed to investigate the relationship between AM and glucose status. Generalized linear model was used to calculate the interaction term of AM and menopause status on FPG and the HOMA index. Interaction plot was used to interpret the significant interaction effect. RESULTS: Women in the later menarche age group (≥18 years) had a 17.7% lower risk of T2DM (95% confidence interval [CI]: 0.712-0.951, P = .008), after adjusting for multiple variables. Further adjustment for body mass index (BMI) completely attenuated this association (odds ratio = 0.884, 95% CI: 0.764-1.024, P = .099). A significant interaction effect of AM and menopause status on T2DM (P = .004) was observed. The adverse effects of menopausal status on FPG and HOMA-2 of insulin resistance decreased with increasing menarche age, and the age ranges were limited to <18 and 9 to 19 years, respectively. CONCLUSIONS: Later menarche was associated with a lower risk of T2DM, and the association appears to be mediated by BMI. More importantly, the adverse effect of menopause status on T2DM was decreased along with increasing menarche age.

7.
Aging (Albany NY) ; 12(1): 672-689, 2020 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-31927536

RESUMO

BACKGROUND: This study is conducted to investigate the protective role of elevated microRNA-375 (miR-375) in dopaminergic neurons in Parkinson's disease through down-regulating transcription factor specificity protein 1 (SP1). RESULTS: The successfully modeled rats with Parkinson's disease showed aggregated neurobehavioral change, increased neuroinflammatory response and oxidative stress, and lowered dopamine content. Parkinson's disease rats treated with overexpressed miR-375 displayed improved neurobehavioral change, ameliorated neuroinflammatory response and oxidative stress, heightened dopamine content and abated neuronal apoptosis by down-regulating SP1. Up-regulation of SP1 reversed the protective effect of upregulated miR-375 on Parkinson's disease. CONCLUSION: Up-regulation of miR-375 ameliorated the damage of dopaminergic neurons, reduced oxidative stress and inflammation in Parkinson's disease by inhibiting SP1. METHODS: Parkinson's disease rat model was established by targeted injection of 6-hydroxydopamine to damage the substantia nigra striatum. The successfully modeled Parkinson's disease rats were intracerebroventricularly injected with miR-375 mimics or pcDNA3.1-SP1. The functions of miR-375 and SP1 in neurobehavioral change, neuroinflammatory response, oxidative stress, dopamine content and expression of apoptosis-related proteins in the substantia nigra of Parkinson's disease rats were evaluated. The target relation of miR-375 and SP1 was confirmed by bioinformatics analysis and dual luciferase reporter gene assay.

8.
Artigo em Inglês | MEDLINE | ID: mdl-31957949

RESUMO

Radical formation is the initial step for conventional radical chemistry. Reported herein is a unified strategy to generate radicals in situ from aromatic ß-ketoesters by using a photocatalyst. Under visible-light irradiation, a small amount of photocatalyst fac-Ir(ppy)3 generates a transient α-carbonyl radical and persistent ketyl radical in situ. In contrast to the well-established approaches, neither stoichiometric external oxidant nor reductant is required for this reaction. The synthetic utility is demonstrated by pinacol coupling of ketyl radicals and benzannulation of α-carbonyl radicals with alkynes to give a series of highly substituted 1-naphthols in good to excellent yields. The readily available photocatalyst, mild reaction conditions, broad substrate scope, and high functional-group tolerance make this reaction a useful synthetic tool.

9.
Soft Matter ; 16(1): 162-169, 2020 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-31774104

RESUMO

A highly stretchable nanocomposite (NC) hydrogel was fabricated via in situ free radical polymerization of acrylamide. In particular, an exfoliated two-dimensional MXene (Ti3C2) nanosheet was utilized as a crosslinker instead of traditional organic crosslinkers. The exfoliated Ti3C2 nanosheets were confirmed by atomic force microscopy (AFM) and dynamic light scattering (DLS) measurements. Compared with traditional organic crosslinked N,N-methylene bisacrylamide (BIS)/polyacrylamide (PAM) hydrogels (fracture strength of 32.0 kPa and elongation of 109.6%), the synthesized Ti3C2/PAM NC hydrogels exhibited greatly improved mechanical properties with fracture strengths of 66.5 to 102.7 kPa, compressive strengths of 400.6 to 819.4 kPa and elongations at break of 2158.6% to 3047.5% as the Ti3C2 content increases from 0.0145% to 0.0436%. The enhanced mechanical performances can be attributed to the honeycomb-like fine structure with uniform pores as well as more flexible polymer chains in NC hydrogel networks. When loaded with drugs, Ti3C2/PAM NC hydrogels exhibited good sustained-release performance, higher drug loading amounts (97.5-127.7 mg g-1) and higher percentage releases (62.1-81.4%), greatly superior to those of the BIS/PAM hydrogel (46.4 mg g-1, 45.0%). Our work reveals the application of MXene materials in the fabrication of NC hydrogels with enhanced mechanical and drug release behaviors.

10.
J Pharm Biomed Anal ; 179: 113013, 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-31806398

RESUMO

The stems of Mahonia fortunei (MF) are commonly used in Chinese Traditional Medicine and contain multiple bioactive compounds, including 3,4,5-trimethoxyphenol-1-O-ß-d-glucopyranoside (1), 5-hydroxypicolinic acid methyl ester (2), acortatarin A (3), syringic acid (4), 9-epi-acortatarin A (5), vomifoliol (6), corydaldine (7), noroxyhydrastinine (8), columbamine (9), jatrorrhizine (10), palmatine (11), berberine (12) and schisandrin (13). The pharmacokinetics of these 13 compounds in the rat plasma were assessed using a novel sensitive, rapid, and specific UPLC-ESI-MS/MS method after oral administration of an aqueous extract of MF stems. Carbamazepine was employed as the internal standard (IS) and all samples were precipitated with acetonitrile. Chromatographic separation was performed on a C18 column using a gradient elution at 0.3 mL/min, with the mobile phase consisting of acetonitrile and 0.06 % formic acid and 5 mM ammonium acetate aqueous solution. The calibration curves showed satisfactory linearity in the examination area (r2 ≥ 0.99). The accuracy, precision, extraction recovery, matrix effect, and stability were within acceptable ranges. The method successfully assessed the pharmacokinetics of these 13 compounds. In vitro, compound 12 exhibited potent inhibitory activity against production of nitric oxide (NO) in the RAW264.7 cell line when stimulated by lipopolysaccharide (LPS), while compounds 7, 12, and 13 were the most potent inhibitors of NO production in the BV2 cell line when stimulated by LPS. The IC50 values of compounds 7, 12 and 13 were 42.81, 20.55 and 22.74 µM. We conclude that these compounds have promise for clinical application, although their synergistic action may be more effective than that by any single compound alone.

11.
Spectrochim Acta A Mol Biomol Spectrosc ; 226: 117582, 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-31629978

RESUMO

Three 5H-benzo[a]phenoxazin-5-one-based (benzoresorufin and nile-red) Cysteine (Cys) detection probes have been comparatively designed and synthesized in this paper. The optical experiments exhibit probe 1b with a crotonoyl group has no response toward Cys; while probes 1a and 1c have the same reaction site (acryloyl group), their optical responses to Cys are quite different. The benzoresorufin-based-probe 1a shows a turn-on fluorescence response (118-fold) to Cys at 631 nm and affords a very low detection limit (DL = 19.8 nM). Compared with probe 1a, the nile-red-based probe 1c displays gradually diminishing fluorescence intensity with increased Cys concentration at 665 nm. And the notable different fluorescence response mechanisms of probes 1a and 1c toward Cys can be interpreted by HRMS and time-dependent density functional theorety (TDDFT) calculations. Furthermore, both of the two probes indicate high sensitivity and selectivity toward Cys over other similar structured amino acids including homocysteine (Hcy) and glutathione (GSH). Further cellular applications of the two probes have been successfully performed in HeLa cells.

12.
J Mol Neurosci ; 70(1): 1-8, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31428919

RESUMO

This study presents two Chinese siblings with a rare neurodevelopmental disorder (NDD) caused by biallelic INTS1 mutations and investigates the clinical features of this disease by means of in silico analysis. Two siblings, an 11-year-old brother and a 5-year-old sister, visited our hospital due to physical retardation and profound intellectual disability. Whole-exome sequencing (WES) was performed for the girl, and Sanger sequencing was used to validate the identified variants. Phenotype correlation analysis and in silico genetic interaction network analysis were performed to investigate genes that could lead to diseases similar to the rare disease in the patients. Growth retardation, distinct intellectual disability, hypertelorism, mild cataract, uneven teeth, abnormal palmar and plantar creases, and dubious genitalia were noted in the sister. No neurological features related to neuropathy were found. The brother showed features and growth delay similar to his sister. Heterozygous novel variants of c.1645A>G,p.Met549Val and c.5881C>T,p.Gln1961* in INTS1 were considered a candidate etiology. Sanger sequencing demonstrated that the variants were inherited from the grandfather and (maternal) grandmother. Phenotype correlation analysis revealed that CTDP1 mutation-induced congenital cataracts-facial dysmorphism-neuropathy (CCFDN) mostly overlapped with the performance of our patients. In silico analysis of the genetic interaction network showed that INTS1 is highly associated with INTS8 and CTDP1. Our study further validated that biallelic INTS1 mutations could bring about the onset of a novel neurodevelopmental disorder.

13.
J Sep Sci ; 43(2): 438-451, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31654554

RESUMO

Citrus reticulata semen, a traditional Chinese medicinal material, has desirable medicinal and dietary properties. In this study, a method combining ultra high performance liquid chromatography with Q Exactive Orbitrap tandem mass spectrometry was established and validated for the identification and analysis of the chemical components of C. reticulata semen for the first time. The evaluation of different retention times and fragmentation characteristics, as well as comparative analysis with the literature, resulted in the identification of 35 chemical constituents, including 21 flavonoids and 14 other compounds. The 21 flavonoids derived from C. reticulata semen were reported for the first time. Seven of the chemical components of C. reticulata semen were quantitatively analyzed using the developed method under the optimal conditions. The results showed that the content of limonin, hesperidin, nobiletin, synephrine, tangeretin, 3,5,6,7,8,3',4'-heptamethoxyflavone and 5-hydroxide-6,7,8,3',4'-pentamethoxyflavone in C. reticulata semen was 11.1666, 0.0404, 0.0092, 0.0255, 0.0087, 0.0010, and 0.0008 mg/g, respectively. This study demonstrated that the ultra high performance liquid chromatography Q Exactive Orbitrap mass spectrometry based method can be used to rapidly and reliably analyze the chemical constituents of C. reticulata semen. These results provide a scientific basis for further studies of C. reticulata semen.

15.
World J Gastrointest Oncol ; 11(11): 1043-1053, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31798784

RESUMO

BACKGROUND: Several models are currently available for predicting the malignancy of pancreatic intraductal papillary mucinous neoplasm (IPMN), namely, the Pancreatic Surgery Consortium (PSC), the Japan Pancreas Society (JPS), the Johns Hopkins Hospital (JHH), and the Japan-Korea (JPN-KOR) models. However, a head-to-head comparison that shows which model is more accurate for this individualized prediction is lacking. AIM: To perform a head-to-head comparison of the four models for predicting the malignancy of pancreatic IPMN. METHODS: A total of 181 patients with IPMN who had undergone surgical resection were identified from a prospectively maintained database. The characteristics of IPMN in patients were recorded from endoscopic ultrasound imaging data and report archives. The performance of all four models was examined using Harrell's concordance index (C-index), calibration plots, decision curve analyses, and diagnostic tests. RESULTS: Of the 181 included patients, 94 were categorized as having benign disease, and the remaining 87 were categorized as having malignant disease. The C-indexes were 0.842 [95% confidence interval (CI): 0.782-0.901], 0.704 (95%CI: 0.626-0.782), 0.754 (95%CI: 0.684-0.824), and 0.650 (95%CI: 0.483-0.817) for the PSC, JPS, JHH, and JPN-KOR models, respectively. Calibration plots showed that the PSC model had the least pronounced departure from ideal predictions. Of the remaining three models, the JPS and JHH models underestimated the probability of malignancy, while the JPN-KOR model overestimated the malignant potential of branch duct-IPMN. Decision curve analysis revealed that the PSC model resulted in a better clinical net benefit than the three other models. Diagnostic tests also showed a higher accuracy (0.801) for the PSC model. CONCLUSION: The PSC model exhibited the best performance characteristics. Therefore, the PSC model should be considered the best tool for the individualized prediction of malignancy in patients with pancreatic IPMN.

16.
Chin J Nat Med ; 17(11): 822-834, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31831129

RESUMO

Angelicae Pubescentis Radix (APR), a widely used traditional Chinese medicine (TCM), is mainly used to treat rheumatism and headache diseases. Angelol B is one of the bioactive constituents of APR with significant anti-inflammatory activity. This paper is aimed to illustrate the metabolites of angelol B in vivo. To achieve this objective, a metabolomics approach based on a rapid and accurate UPLC-Q-TOF-MS method was used to detect the metabolites of Angelol B in rat. A gradient elution system (ACN and 0.1% formic acid water) equipped with an Agilent SB-C18 column (1.8 µm, 2.1 mm × 50 mm) to complete the separation. Scanning area at m/z 100.800 operated on an electrospray ionization (ESI). The data were collected in both positive and negative ion mode and analyzed by the Masslynx 4.1 and SIMCA 13.0 software. A total of 31 metabolites including 20 phase I and 11 phase II. metabolites were identified. Their structure and fragmentation process were deduced based on the MS and MS/MS data. All of thirty-one metabolites are new compounds based on the search of SCI-Finder database.

17.
J Neuroinflammation ; 16(1): 249, 2019 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-31796106

RESUMO

BACKGROUND: Inflammation can induce cognitive dysfunction in patients who undergo surgery. Previous studies have demonstrated that both acute peripheral inflammation and anaesthetic insults, especially isoflurane (ISO), are risk factors for memory impairment. Few studies are currently investigating the role of ISO under acute peri-inflammatory conditions, and it is difficult to predict whether ISO can aggravate inflammation-induced cognitive deficits. HDACs, which are essential for learning, participate in the deacetylation of lysine residues and the regulation of gene transcription. However, the cell-specific mechanism of HDACs in inflammation-induced cognitive impairment remains unknown. METHODS: Three-month-old C57BL/6 mice were treated with single versus combined exposure to LPS injected intraperitoneally (i.p.) to simulate acute abdominal inflammation and isoflurane to investigate the role of anaesthesia and acute peripheral inflammation in cognitive impairment. Behavioural tests, Western blotting, ELISA, immunofluorescence, qRT-PCR, and ChIP assays were performed to detect memory, the expressions of inflammatory cytokines, HDAC2, BDNF, c-Fos, acetyl-H3, microglial activity, Bdnf mRNA, c-fos mRNA, and Bdnf and c-fos transcription in the hippocampus. RESULTS: LPS, but not isoflurane, induced neuroinflammation-induced memory impairment and reduced histone acetylation by upregulating histone deacetylase 2 (HDAC2) in dorsal hippocampal CaMKII+ neurons. The hyperexpression of HDAC2 in neurons was mediated by the activation of microglia. The decreased level of histone acetylation suppressed the transcription of Bdnf and c-fos and the expressions of BDNF and c-Fos, which subsequently impaired memory. The adeno-associated virus ShHdac2, which suppresses Hdac2 after injection into the dorsal hippocampus, reversed microglial activation, hippocampal glutamatergic BDNF and c-Fos expressions, and memory deficits. CONCLUSIONS: Reversing HDAC2 in hippocampal CaMKII+ neurons exert a neuroprotective effect against neuroinflammation-induced memory deficits.

18.
Menopause ; 26(11): 1265-1271, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31688573

RESUMO

OBJECTIVE: The aim of the study was to determine if early menarche is associated with an increased risk of type 2 diabetes mellitus (T2DM) in rural Chinese women and to estimate the proportion that can be attributed to adiposity. METHODS: A total of 15,346 postmenopausal women were enrolled in this study. Logistic regression and restricted cubic spline analysis were performed to estimate the relationship between age at menarche and T2DM. Mediation analysis was used to investigate whether the association was mediated by body mass index (BMI). RESULTS: After adjusting for multiple confounders, the early menarche group (≤14 y) had a higher risk of T2DM (odds ratio [OR] = 1.21; 95% CI = 1.06-1.38; P = 0.004) compared with the reference group (16-17 y), whereas the late onset group (≥19 y) had a lower risk of T2DM (OR = 0.78; 95% CI = 0.66-0.92; P = 0.003). BMI partially mediated the association between age at menarche and T2DM, and the proportion of the effect was 28%. CONCLUSIONS: Early menarche increases the risk of T2DM, whereas later menarche decreases the risk. The association seems to be partially mediated by BMI.

19.
Front Mol Neurosci ; 12: 246, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31708739

RESUMO

Brain-derived neurotrophic factor (BDNF) is essential for cognitive and memory functions. Abnormal BDNF expression in the central nervous system may impair these functions. Anaesthesia and surgery can induce perioperative neurocognitive disorders (PND). Clinical studies show that BDNF expression is decreased in patients presenting with cognitive impairment after anaesthesia and surgery. However, the molecular mechanism is still unclear. Epigenetic regulation plays an important role in cognition. The hypermethylation of H3K9 is crucial for transcriptional silencing and the onset of cognitive disorders. Here, we hypothesised that H3K9 trimethylation repressed BDNF expression and impaired memory formation or recall during anaesthesia and surgery. Laparotomy under isoflurane inhalation anaesthesia, behavioural tests, Western blotting, quantitative real-time reverse-transcription polymerase chain reaction (qRT-PCR), chromatin immunoprecipitation (ChIP), and immunohistochemistry were used in this study. BDNF expression was decreased in the hippocampus after anaesthesia and surgery. Cognitive impairment affected memory formation but not recall. The trimethylation of H3K9 downregulated BDNF expression. The overexpression of BDNF or use of exogenous BDNF improved the impairment of memory formation caused by anaesthesia and surgery. Therefore, inhibiting H3K9 trimethylation and increasing the expression of BDNF may help prevent PND in the clinical setting.

20.
Molecules ; 24(22)2019 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-31718071

RESUMO

Psoralen (P) and isopsoralen (IP) are the main active ingredients in the dried fruit of Psoralen corylifolia L. (PC), with a wide range of pharmacology activities. The intestinal bacteria biotransformation plays a central role in the metabolism of the complex ingredients in traditional Chinese medicine (TCM). Our study aimed to investigated the metabolic profile of P and IP in the intestinal condition, co-cultured with human fecal bacteria anaerobically. Four bio-transforming products were obtained, including 6,7-furano-hydrocoumaric acid (P-1) and 6,7-furano-hydro- coumaric acid methyl ester (P-2), which transformed from P, and 5,6-furano-hydrocoumaric acid (IP-1) and 5,6-furano-hydrocoumaric acid methyl ester (IP-2), which were transformed from IP. It is worth mentioning that IP-2 is a new compound that has not been published. Their structures were analyzed based on their spectroscopic data. Moreover, a highly sensitive ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method was used to characterize the metabolic pathways of P, IP, and their bio-transforming products in the reaction samples. In addition, the dampening effects against the oxidative stress of P, IP, and their bio-transforming products by human intestinal flora were estimated in vitro via the human colorectal cells (HCT116) and heterogeneous human epithelial colorectal adenocarcinoma cells (Caco-2) cell lines. The results showed that the metabolites have stronger activity than P and IP, which possibly provides a basis for elucidating the treating mechanisms of PC extract against inflammatory bowel disease.

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