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1.
Int J Mol Sci ; 20(17)2019 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-31480391

RESUMO

Salinity is one of the most decisive environmental factors threatening the productivity of crop plants. Understanding the mechanisms of plant salt tolerance is critical to be able to maintain or improve crop yield under these adverse environmental conditions. Plant membranes act as biological barriers, protecting the contents of cells and organelles from biotic and abiotic stress, including salt stress. Alterations in membrane lipids in response to salinity have been observed in a number of plant species including both halophytes and glycophytes. Changes in membrane lipids can directly affect the properties of membrane proteins and activity of signaling molecules, adjusting the fluidity and permeability of membranes, and activating signal transduction pathways. In this review, we compile evidence on the salt stress responses of the major membrane lipids from different plant tissues, varieties, and species. The role of membrane lipids as signaling molecules in response to salinity is also discussed. Advances in mass spectrometry (MS)-based techniques have largely expanded our knowledge of salt-induced changes in lipids, however only a handful studies have investigated the underlying mechanisms of membrane lipidome regulation. This review provides a comprehensive overview of the recent works that have been carried out on lipid remodeling of plant membranes under salt treatment. Challenges and future perspectives in understanding the mechanisms of salt-induced changes to lipid metabolisms are proposed.

2.
JAMA ; 2019 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-31475726

RESUMO

Importance: The relationship between exposure to lower low-density lipoprotein cholesterol (LDL-C) and lower systolic blood pressure (SBP) with the risk of cardiovascular disease has not been reliably quantified. Objective: To assess the association of lifetime exposure to the combination of both lower LDL-C and lower SBP with the lifetime risk of cardiovascular disease. Design, Setting, and Participants: Among 438 952 participants enrolled in the UK Biobank between 2006 and 2010 and followed up through 2018, genetic LDL-C and SBP scores were used as instruments to divide participants into groups with lifetime exposure to lower LDL-C, lower SBP, or both. Differences in plasma LDL-C, SBP, and cardiovascular event rates between the groups were compared to estimate associations with lifetime risk of cardiovascular disease. Exposures: Differences in plasma LDL-C and SBP compared with participants with both genetic scores below the median. Genetic risk scores higher than the median were associated with lower LDL-C and lower SBP. Main Outcomes and Measures: Odds ratio (OR) for major coronary events, defined as coronary death, nonfatal myocardial infarction, or coronary revascularization. Results: The mean age of the 438 952 participants was 65.2 years (range, 40.4-80.0 years), 54.1% were women, and 24 980 experienced a first major coronary event. Compared with the reference group, participants with LDL-C genetic scores higher than the median had 14.7-mg/dL lower LDL-C levels and an OR of 0.73 for major coronary events (95% CI, 0.70-0.75; P < .001). Participants with SBP genetic scores higher than the median had 2.9-mm Hg lower SBP and an OR of 0.82 for major coronary events (95% CI, 0.79-0.85, P < .001). Participants in the group with both genetic scores higher than the median had 13.9-mg/dL lower LDL-C, 3.1-mm Hg lower SBP, and an OR of 0.61 for major coronary events (95% CI, 0.59-0.64; P < .001). In a 4 × 4 factorial analysis, exposure to increasing genetic risk scores and lower LDL-C levels and SBP was associated with dose-dependent lower risks of major coronary events. In a meta-regression analysis, combined exposure to 38.67-mg/dL lower LDL-C and 10-mm Hg lower SBP was associated with an OR of 0.22 for major coronary events (95% CI, 0.17-0.26; P < .001), and 0.32 for cardiovascular death (95% CI, 0.25-0.40; P < .001). Conclusions and Relevance: Lifelong genetic exposure to lower levels of low-density lipoprotein cholesterol and lower systolic blood pressure was associated with lower cardiovascular risk. However, these findings cannot be assumed to represent the magnitude of benefit achievable from treatment of these risk factors.

3.
Hepatology ; 2019 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-31506976

RESUMO

Obesity-induced chronic inflammation is a key component in the pathogenesis of nonalcoholic fatty liver disease (NAFLD) and insulin resistance. Increased secretion of pro-inflammatory cytokines by macrophages in metabolic tissues promotes disease progression. In the diet induced obesity mouse (DIO) model, activation of liver resident macrophages, or Kupffer cells (KC), drives inflammatory responses, which recruits circulating macrophages and promotes fatty liver development, and ultimately contributes to impaired hepatic insulin sensitivity. Hepatic macrophage express the highest level of Vitamin D receptor (VDR) among non-parenchymal cells, while VDR expression is very low in hepatocytes. VDR activation exerts anti-inflammatory effects in immune cells. Here we found that VDR activation exhibits strong anti-inflammatory effects in mouse hepatic macrophages, including those isolated from DIO livers, while mice with genetic loss of Vdr developed spontaneous hepatic inflammation at 6 months of age. Under the chronic inflammation conditions of the DIO model, VDR activation by the vitamin D analog calcipotriol reduced liver inflammation and hepatic steatosis, significantly improving insulin sensitivity. The hyperinsulinemic euglycemic clamp revealed that VDR activation greatly increased the glucose infusion rate, while hepatic glucose production was remarkably decreased. Glucose uptake in muscle and adipose did not show similar effects, suggesting that improved hepatic insulin sensitivity is the primary contributor to the beneficial effects of VDR activation. Finally, specifically ablating liver macrophages by treatment with clodronate liposomes largely abolished the beneficial metabolic effects of calcipotriol, confirming that VDR activation in liver macrophages is required for the anti-diabetic effect. Conclusion: Activation of liver macrophage VDR by vitamin D ligands ameliorates liver inflammation, steatosis and insulin resistance. Our results suggest novel therapeutic paradigms for treatment of NAFLD and T2D.

4.
Sci Rep ; 9(1): 11153, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31371750

RESUMO

Although 70-80% of newly diagnosed ovarian cancer patients respond to first-line therapy, almost all relapse and five-year survival remains below 50%. One strategy to increase five-year survival is prolonging time to relapse by improving first-line therapy response. However, no biomarker today can accurately predict individual response to therapy. In this study, we present analytical and prospective clinical validation of a new test that utilizes primary patient tissue in 3D cell culture to make patient-specific response predictions prior to initiation of treatment in the clinic. Test results were generated within seven days of tissue receipt from newly diagnosed ovarian cancer patients obtained at standard surgical debulking or laparoscopic biopsy. Patients were followed for clinical response to chemotherapy. In a study population of 44, the 32 test-predicted Responders had a clinical response rate of 100% across both adjuvant and neoadjuvant treated populations with an overall prediction accuracy of 89% (39 of 44, p < 0.0001). The test also functioned as a prognostic readout with test-predicted Responders having a significantly increased progression-free survival compared to test-predicted Non-Responders, p = 0.01. This correlative accuracy establishes the test's potential to benefit ovarian cancer patients through accurate prediction of patient-specific response before treatment.

5.
Geriatr Nurs ; 2019 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-31466807

RESUMO

This study was designed to examine the feasibility of a caregiving self-management support program developed for caregivers of relatives with dementia in Shanghai. A total of 41 caregivers were recruited for a quasi-experimental study. The experimental group of 26 participants attended six bi-weekly social support group sessions. The control group of 15 participants received three monthly telephone instructions. All of participants received an illustrated caregiver educational booklet and three educational presentations during a six-month follow-up period. The results demonstrated a stronger sense of self-efficacy regarding the gathering of information about dementia care in both study groups compared to the baseline data. Caregivers participating in the group sessions reported better health-related quality of life, improved responses to behavioral disturbances, and efficacy in the management of stress than those who received telephone instructions. This study provided some preliminary information regarding ways to improve self-management for the target population in mainland China.

6.
J Biomed Nanotechnol ; 15(10): 2090-2099, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31462373

RESUMO

Chemodynamic therapy based on Fenton or Fenton-like reactions is an emerging cancer therapy that has attracted considerable attention due to its high selectivity for tumors. However, the low catalytic efficiency of the Fenton or Fenton-like agent limits its therapeutic effect. Combination therapies based on chemodynamic therapy using "all-in-one" agents show great potential for cancer treatment. In this study, W18O49 nanorods with strong near-infrared absorption and excellent Fenton-like reaction performance were prepared, and their application in photoacoustic imaging-guided photothermal-chemodynamic combination cancer therapy was explored. First, hydrophobic W18O49 nanorods were synthesized via a one-step pyrolysis method. Hydrophilic W18O49 nanorods were then prepared via hydrophobic self-assembly between oleyl amine-coated W18O49 nanorods and an amphiphilic polymer. The W18O49 nanorods exhibited good photoacoustic, photothermal, and chemodynamic performance in vitro along with good photoacoustic imaging contrast and excellent therapeutic effect in photothermal-chemodynamic combination cancer therapy in vivo. This study provides a low-cost and easy-to-prepare agent for photothermal-chemodynamic combination therapy and promotes the application of photothermal-chemodynamic combination therapy in cancer treatment.


Assuntos
Nanotubos , Neoplasias , Técnicas Fotoacústicas , Terapia Combinada , Humanos , Polímeros
7.
J Chromatogr A ; : 460378, 2019 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-31376981

RESUMO

Danhong Injection (DHI) is a Chinese medicine patent drug to treat cardiovascular diseases. It is derived from the herbal medicines Dan-shen and Hong-hua. The bioactive compounds of DHI are polar phenolic acids and flavonoid glycosides. Thus far, the contents of major compounds in DHI are not well understood, and the identification of minor compounds lacks rapid methods. In this work, quantitative and qualitative analyses of DHI compounds were performed using ultra-high performance liquid chromatography coupled with orbitrap mass spectrometry (UHPLC/orbitrap-MS). DHI was separated on an Acquity HSS T3 column (1.8 µm, 100 mm × 2.1 mm) and eluted with acetonitrile-water (containing 0.1% formic acid) to determine the contents of 12 compounds within 6 min. The method was fully validated according to the ICH guidance. To identify the minor compounds, an ion statistics-based strategy was used to dig for 4 filtering ions and 6 diagnostic ions from 22 reference standards. A total of 117 compounds, including 76 phenolic acids, 20 flavonoids, and 21 other compounds were tentatively identified. The poor stability of salvianolic acid A upon storage was also discussed.

8.
Acad Psychiatry ; 2019 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-31396881

RESUMO

OBJECTIVE: The primary purpose of this study was to evaluate the factorial structure of the short-form version of the self-compassion scale (SCS-SF) and validate its use with medical students. METHODS: Two hundred medical students completed an electronic questionnaire containing the 12-item SCS-SF and the 16-item Oldenburg burnout inventory. The authors performed reliability and confirmatory factor analyses (CFA) to evaluate the internal consistency and factorial structure of the SCS-SF scores, and correlational analyses to examine relationships of self-compassion with student engagement and exhaustion. RESULTS: The internal consistency of the SCS-SF was 0.86. Self-compassion scores were positively correlated with engagement scores (r = 0.24; p < 0.01) and negatively correlated with exhaustion scores (r = - 0.44; p < 0.001). The CFA results for the two-factor model (formed by three positive and three negative components) indicated an improved fit over the single-factor model. The positive factor (self-compassion) was positively correlated with engagement scores (r = 0.17; p < 0.05) and negatively correlated with exhaustion scores (r = - 0.32; p < 0.001). The negative factor (self-criticism) was negatively correlated with engagement scores (r = - 0.25; p < 0.001) and positively correlated with exhaustion scores (r = 0.44; p < 0.001). CONCLUSIONS: The SCS-SF scores had good internal consistency and expected relations with student engagement and exhaustion. Although the single, general self-compassion factorial structure had an acceptable fit with the data, the hierarchical two-factor structure of the SCS-SF provides support for the idea that distinguishing between self-compassion and self-criticism in medical students may be important.

9.
Pharmacol Rep ; 71(5): 968-975, 2019 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-31470293

RESUMO

BACKGROUND: We aimed to investigate whether the facilitating effect of H2S on the baroreceptor reflex is associated with the GABAA receptor, KATP channel and L-type Ca2+ channel pathway. METHODS: Spontaneously hypertensive rats (SHRs) and Wistar Kyoto (WKY) rats were used to investigate the facilitating effect of H2S on the baroreceptor reflex by perfusing the isolated carotid sinus. The mechanism by which H2S facilitated the baroreceptor reflex was determined by using Bay K8644 (an agonist of calcium channels), glibenclamide (Gli, a KATP channel blocker), and picrotoxin (PIC, a blocker of γ-aminobutyric acid [GABA]A receptor). RESULTS: As compared with WKY rats, SHRs showed impaired baroreceptor reflex sensitivity, as demonstrated by a right and upward shift of the functional curve for the intrasinus pressure-arterial blood pressure relation. H2S perfusion (25, 50, or 100 µmol/L) dose-dependently ameliorated the impaired sensitivity of the baroreceptor reflex. Bay K8644 (500 nmol/L), Gli (20 µmol/L) and PIC (50 µmol/L) all prevented H2S ameliorating the impaired baroreceptor reflex. CONCLUSIONS: H2S facilitating the baroreceptor reflex might be associated with activating the GABAA receptor, opening the KATP channel, and closing the L-type Ca2+ channel. These areas should provide new targets for preventing and treating hypertension.

11.
Int J Biol Sci ; 15(7): 1488-1499, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31337978

RESUMO

Thyroid hormone receptor interactor 13 (TRIP13) is a crucial regulator of the spindle apparatus checkpoint and double-stranded break repair. The abnormal expression of TRIP13 was recently found in several human cancers, whereas the role of TRIP13 in the development of bladder cancer (BCa) has not been fully elucidated. Here, we reported that TRIP13 expression was elevated in BCa tissues compared with normal bladder tissues. Notably, the increased expression of TRIP13 was correlated with advanced tumor stage, lymph node metastasis, distant metastasis and reduced survival in BCa patients. Knockdown of TRIP13 in bladder cancer cells suppressed proliferation, induced cell cycle arrest, promoted apoptosis, and impaired cell motility, ultimately inhibiting tumor xenograft growth. Mechanistic investigations revealed that TRIP13 directly bound to epidermal growth factor receptor (EGFR), modulating the EGFR signaling pathway. Furthermore, TRIP13 expression was positively correlated with EGFR expression in BCa specimens, and the high expression of both TRIP13 and EGFR predicted poor survival. Overall, our results underscore the crucial role of TRIP13 in the tumorigenesis of BCa and provide a novel biomarker and therapeutic target for BCa treatment.

12.
Biochem Biophys Res Commun ; 516(4): 1265-1271, 2019 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-31301767

RESUMO

Leukemia remains a fatal disease for most patients and effective therapeutic strategies are urgently required. Typhaneoside (TYP) is a major flavonoid in the extract of Pollen Typhae, showing significant biological and pharmacological effects. In the present study, we explored the effects of TYP on acute myeloid leukemia (AML) progression. The results indicated that TYP markedly reduced the cell viability of AML cells and arrested the cell cycle at the G2/M phase by regulating the expression of associated proteins. In addition, TYP significantly induced apoptosis in AML cells by promoting the activation of Caspase-3. Intracellular and mitochondrial reactive oxygen species (ROS) accumulation were highly detected in AML cells after treatment with TYP. Moreover, TYP clearly induced ferroptosis in AML cells, and this process was iron-dependent and attendant with mitochondrial dysfunction. We also found that TYP significantly triggered autophagy in AML cells by promoting the activation of AMP-activated protein kinase (AMPK) signaling, contributing to ferritin degradation, ROS accumulation and ferroptotic cell death ultimately. In conclusion, the findings above provided solid evidences that TYP could be a promising therapeutic agent to prevent AML progression by inducing apoptosis, ROS production, autophagy and ferroptosis.

13.
J Cell Physiol ; 2019 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-31264214

RESUMO

This study is launched to investigate the effect of lentivirus-mediated microRNA-26a (miR-26a)-modified neural stem cells (NSCs) in brain injury in rats with cerebral palsy (CP). The successfully constructed miR-26a lentivirus expression vector and empty vector virus were used to modify NSCs. The model of CP with ischemia and anoxia was established in rats. NSCs and miR-26a-NSCs were stereoscopically injected into the cerebral cortex of the modeled rats, respectively. The survival and migration of NSCs infected with recombinant lentivirus expressing green fluorescence in vivo was observed under a light microscope. The neurobehavioral functions, morphology, and ultrastructure of cerebral cortex and hippocampus, apoptosis of brain cells, expression of apoptosis-related protein caspase-3 and Bax, together with the expression of the glial fibrillary acidic protein (GFAP) in cerebral cortex and hippocampus were determined. Expression of miR-26a in NSCs infected with plVTHM-miR-26a increased significantly. After NSCs transplantation, the neurobehavioral status of CP rats was improved, the degree of brain pathological injury was alleviated, the apoptotic index of cells in cerebral cortex and hippocampus and the expression of the apoptotic protein (caspase-3 and Bax) were decreased, the expression of GFAP were significantly decreased. After miR-26a-NSCs transplantation, these aforementioned results further improved or decreased. Our study suggests that miR-26a-modified NSCs mediated by lentivirus can improve brain injury, inhibit apoptosis of brain cells and activation of astrocytes in CP rats.

14.
Opt Lett ; 44(12): 3098-3101, 2019 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-31199390

RESUMO

We report, to the best of our knowledge, the first experimental observation of higher-charge vortex solitons and vector vortex solitons in lead glass with strongly thermal nonlocal nonlinearity. A higher-charge vortex soliton with a topological charge of l=4 and a vector vortex soliton consisting of two orthogonally polarized vortex components, with charges l1=1 and l2=4, were observed at several times of diffraction length. We show that the ring profiles and the carried topological charges of the two incoherently coupled vortex components can be preserved. We also numerically find that the stability of the higher-charge vortex can be enhanced by co-propagating a stable, single-charge vortex.

15.
Medicine (Baltimore) ; 98(24): e15938, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31192929

RESUMO

The aim of this study was to investigate the dose optimization strategy for the sacrum to reduce the risk of pelvic insufficiency fracture (PIF).Using a retrospective study design, we analyzed data from 28 patients with cervical cancer who underwent postoperative adjuvant radiotherapy in our department from June 2017 to January 2018. Among these patients, 20 (71.4%) underwent external beam radiation therapy in the pelvic lymphatic drainage area (node-negative patients). Overall, 8 patients (28.6%) underwent radiotherapy in the pelvic lymphatic drainage area with a simultaneous integrated boost (node-positive patients). Furthermore, 20 patients were assigned to 2 groups of plans according to the prescribed doses of 5000 and 4500 cGy/25. Each group had 3 plans according to 3 different dose limit conditions: "pelvic bones and sacrum unlimited," "pelvic bones limited," and "pelvic bones + sacrum limited." The irradiation dose of the sacrum and pelvis was analyzed in three limited optimization models.The planning target volume conformity index and homogeneity index, based on different optimization modes in the 4500 and 5000 cGy plans, showed no significant differences. The D50% and Dmean of the pelvis + sacrum limited mode were significantly lower than those of the pelvic limited mode (P < .001). The dose of the sacrum and pelvis in the 4500 cGy plan in the lymphatic drainage area was significantly lower than that of the 5000 cGy plan (P < .001). In the lymph node boost group, the irradiation dose of the sacrum and pelvis was significantly increased (P ≤ .001).Increasing the limitation of the sacrum, on the basis of pelvic bone limitation, in cervical cancer intensity-modulated radiation therapy can significantly reduce the dose to the sacrum. Compared with the dose of 5000 cGy to the lymphatic drainage area, the dose of 4500 cGy was the largest influencing factor to reduce the dose to the sacrum.


Assuntos
Pelve/efeitos da radiação , Planejamento da Radioterapia Assistida por Computador/métodos , Radioterapia de Intensidade Modulada/métodos , Sacro/efeitos da radiação , Neoplasias do Colo do Útero/radioterapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Pessoa de Meia-Idade , Doses de Radiação , Dosagem Radioterapêutica , Radioterapia Adjuvante , Estudos Retrospectivos , Resultado do Tratamento
16.
Microb Cell Fact ; 18(1): 107, 2019 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-31196093

RESUMO

BACKGROUND: Microbial mutagenesis is an important avenue to acquire microbial strains with desirable traits for industry application. However, mutagens either chemical or physical used often leads narrow library pool due to high lethal rate. The T4 DNA ligase is one of the most widely utilized enzymes in modern molecular biology. Its contribution to repair chromosomal DNA damages, therefore cell survival during mutagenesis will be discussed. RESULTS: Expression of T4 DNA ligase in vivo could substantially increase cell survival to ionizing radiation in multiple species. A T4 mediated survival-coupled mutagenesis approach was proposed. When polyhydroxybutyrate (PHB)-producing E. coli with T4 DNA ligase expressed in vivo was subjected to ionizing radiation, mutants with improved PHB production were acquired quickly owing to a large viable mutant library generated. Draft genome sequence analysis showed that the mutants obtained possess not only single nucleotide variation (SNV) but also DNA fragment deletion, indicating that T4 DNA ligase in vivo may contribute to the repair of DNA double strand breaks. CONCLUSIONS: Expression of T4 DNA ligase in vivo could notably enhance microbial survival to excess chromosomal damages caused by various mutagens. Potential application of T4 DNA ligase in microbial mutagenesis was explored by mutating and screening PHB producing E. coli XLPHB strain. When applied to atmospheric and room temperature plasma (ARTP) microbial mutagenesis, large survival pool was obtained. Mutants available for subsequent screening for desirable features. The use of T4 DNA ligase we were able to quickly improve the PHB production by generating a larger viable mutants pool. This method is a universal strategy can be employed in wide range of bacteria. It indicated that traditional random mutagenesis became more powerful in combine with modern genetic molecular biology and has exciting prospect.

17.
Biosci Rep ; 39(6)2019 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-31189745

RESUMO

Apocynum venetum is an eco-economic plant that exhibits high stress resistance. In the present paper, we carried out a whole-genome survey of A. venetum in order to provide a foundation for its whole-genome sequencing. High-throughput sequencing technology (Illumina NovaSep) was first used to measure the genome size of A. venetum, and bioinformatics methods were employed for the evaluation of the genome size, heterozygosity ratio, repeated sequences, and GC content in order to provide a foundation for subsequent whole-genome sequencing. The sequencing analysis results indicated that the preliminary estimated genome size of A. venetum was 254.40 Mbp, and its heterozygosity ratio and percentage of repeated sequences were 0.63 and 40.87%, respectively, indicating that it has a complex genome. We used k-mer = 41 to carry out a preliminary assembly and obtained contig N50, which was 3841 bp with a total length of 223949699 bp. We carried out further assembly to obtain scaffold N50, which was 6196 bp with a total length of 227322054 bp. We performed simple sequence repeat (SSR) molecular marker prediction based on the A. venetum genome data and identified a total of 101918 SSRs. The differences between the different types of nucleotide repeats were large, with mononucleotide repeats being most numerous and hexanucleotide repeats being least numerous. We recommend the use of the '2+3' (Illumina+PacBio) sequencing combination to supplement the Hi-C technique and resequencing technique in future whole-genome research in A. venetum.

18.
J Exp Med ; 216(8): 1944-1964, 2019 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-31196982

RESUMO

High bone mass (HBM) is usually caused by gene mutations, and its mechanism remains unclear. In the present study, we identified a novel mutation in the long noncoding RNA Reg1cp that is associated with HBM. Subsequent analysis in 1,465 Chinese subjects revealed that heterozygous Reg1cp individuals had higher bone density compared with subjects with WT Reg1cp Mutant Reg1cp increased the formation of the CD31hiEmcnhi endothelium in the bone marrow, which stimulated angiogenesis during osteogenesis. Mechanistically, mutant Reg1cp directly binds to Krüppel-like factor 3 (KLF3) to inhibit its activity. Mice depleted of Klf3 in endothelial cells showed a high abundance of CD31hiEmcnhi vessels and increased bone mass. Notably, we identified a natural compound, Ophiopogonin D, which functions as a KLF3 inhibitor. Administration of Ophiopogonin D increased the abundance of CD31hiEmcnhi vessels and bone formation. Our findings revealed a specific mutation in lncRNA Reg1cp that is involved in the pathogenesis of HBM and provides a new target to treat osteoporosis.

19.
ACS Appl Mater Interfaces ; 11(23): 21184-21193, 2019 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-31117467

RESUMO

Hydrogels based on supramolecular noncovalent interactions have attracted great research interest but are still limited by relatively low mechanical strength and performance deterioration at subzero temperatures because of the formation of ice crystallization. In this study, an antifreezing and mechanically strong gelatin supramolecular organohydrogel is prepared via a simple strategy of immersing a gelatin pre-hydrogel in the citrate (Cit) water/glycerol mixture solution. In the organohydrogel, a part of water molecules are replaced by glycerol, which inhibits the formation of ice crystallization even at extremely low temperature. In addition, the formation of noncovalent interactions such as the hydrophobic aggregation induced by the salting-out effect, ionic interactions between the -NH3+ of gelatin and Cit3- anions, and hydrogen bonding between gelatin chains and glycerol endows the organohydrogels with high mechanical strength and toughness. The supramolecular organohydrogel can maintain its mechanical flexibility even at -80 °C or be stored for a long time. Moreover, the nature of noncovalent interactions endows the organohydrogel with intriguing thermoplasticity, good healable ability, and excellent adhesive behavior at various substrate surfaces.

20.
Artigo em Inglês | MEDLINE | ID: mdl-31121335

RESUMO

OBJECTIVES: This study aimed to investigated the molecular mechanism conferring Amikacin (AMK) resistance among M. abscessus clinical isolates. METHODS: A total of 194M. abscessus clinical isolates were collected from patients with lung disease during 2012 to 2017. AMK susceptibility was determined by the broth microdilution method. Whole-genome data were used for the identification of the mutations in resistance-associated genes. qRT-PCR was performed to measure the gene transcriptional level. RESULTS: AMK showed high in vitro killing activity against M. abscessus, with MIC50 of 8 mg/L and MIC90 of 16 mg/L. Five (2.6%) isolates were resistant to AMK (MIC > 1024 mg/L). Of the 5 AMK-resistant isolates, 4 (80%) harbored resistance-associated A1408 G rrs mutation. qRT-PCR analysis showed that most of the AMK-resistant isolates (4/5, 80%) had overexpression of transcriptional regulator gene whiB7 and multidrug-efflux transporter gene tap. However, the overexpression of aminoglycoside-modifying enzyme gene eis2 was only observed in one (20%) AMK-resistant isolate. CONCLUSION: The AMK resistance rate in M. abscessus clinical strains isolated in this study was low. Mutation of A1408 G in rrs and overexpression of WhiB7 and Tap were the predominant mechanisms of AMK resistance in M. abscessus.

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