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1.
Clin Epigenetics ; 12(1): 37, 2020 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-32122390

RESUMO

BACKGROUND: Emerging evidence has shown that MUC1 and TFF2 play crucial roles in the H. pylori-infected pathogenesis of gastric cancer (GC). A recent study revealed that H. pylori infection induced obviously increased Tff2 methylation levels in Muc1-/- mice compared with controls. However, little is known of the molecular mechanism on MUC1 regulating the expression of TFF2. METHODS: We conducted a correlation analysis of MUC1 and TFF2 in public databases and our adjacent GC tissues. Besides, MUC1 overexpression vector or small interfering RNA (siRNA) was transfected into GC cells to assess the change in TFF2 expression. Furthermore, the methylation status of TFF2 was measured by bisulfite sequencing PCR (BSP). RESULTS: The expression of MUC1 was significantly lower in non-cardia and cardia tumor tissues than that in normal tissues. Downregulation of TFF2 expression was also observed in GC tissues. In addition, we found that MUC1 expression was positively associated with TFF2 expression in GC tissues, especially among GC patients with H. pylori infection. Overexpression of MUC1 in BGC-823 and SGC-7901 cell lines substantially increased the TFF2 expression, whereas knockdown of MUC1 reverted this effect. Moreover, MUC1 was negatively related to the methylation of TFF2 in the co-expression analysis. The results of BSP experiments showed that compared with negative vector group, the methylation level of TFF2 was decreased in GC cells transfected with MUC1 overexpression vector. Additionally, survival analysis indicated that GC patients with lower level of MUC1 or TFF2 had a worse outcome. CONCLUSION: Our results indicated that MUC1 was associated with the methylation of TFF2, which may have implications for TFF2 expression in GC. These findings warrant further research toward the underlying mechanism of MUC1 influenced the TFF2 methylation.

2.
Artigo em Inglês | MEDLINE | ID: mdl-32116018

RESUMO

In the early proximal tubule, the Na+-glucose cotransporter SGLT2 mediates the bulk of renal glucose reabsorption. Gene deletion in mice (Sglt2-/-) was used to determine the role of SGLT2 in acute kidney injury (AKI) induced by bilateral ischemia-reperfusion (IR). In Sglt2-/- and littermate wild-type mice (WT), plasma creatinine increased similarly on day 1 (D1) after IR. This was associated with an equal increase in both genotypes in urinary KIM-1-to-creatinine ratio, a tubular injury marker, and similarly reduced urine osmolality and increased plasma osmolality, indicating impaired urine concentration. In both IR groups, FITC-sinistrin GFR was equally reduced on D14 and plasma creatinine was similarly and incompletely restored on D23. In Sglt2-/--IR, fractional urinary glucose excretion was increased on D1 but reduced and associated with normal renal Sglt1 mRNA expression on D23, suggesting temporary SGLT1 suppression. In WT-IR, renal Sglt1 mRNA was likewise normal on D23, while Sglt2 mRNA was reduced by 57%. In both genotypes IR equally reduced urine osmolality and renal mRNA expression of Na-2Cl-K cotransporter NKCC2 and renin on D23, suggesting thick ascending limb dysfunction, and similarly increased renal mRNA expression of markers of injury, inflammation, oxidative stress, and fibrosis (KIM-1, NGAL, MCP-1, TGFB1, NOX2, type 1 collagen). This was associated with equal increases in kidney histological damage scores and similar degree of capillary loss in both genotypes. The data indicate that genetic deletion of SGLT2 did not protect the kidneys in the initial injury phase or the subsequent recovery phase in a mouse model of IR-induced AKI.

3.
Transfus Apher Sci ; : 102743, 2020 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-32139282

RESUMO

OBJECTIVE: To analyze the impact of donor- and recipient-related factors on Graft-versus-host disease (GVHD) and overall survival of transplantation from matched sibling donors. METHOD: we retrospectively analyzed the clinical features of 68 consecutive hematological patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) from matched sibling from 2011 and 2017. RESULTS: The incidence of Ⅱ- Ⅳacute GVHD (aGVHD) and chronic GVHD (cGVHD) after transplantation was 13.6 % and 19.7 %, respectively. We also noted the donor and recipient characteristics had no impact on Ⅱ- Ⅳ aGVHD incidence.We found sex mismatch (F-M) did not increase the risk of cGVHD in the model if a female donor was younger than 30 years (P = 1.000), but cGVHD increased if the female donor was ≥30 years (P = 0.002). Recipients≥40 years undergoing HCT from donors ≥30 years were at higher risk for cGVHD (P = 0.021). Development of Ⅱ- Ⅳ aGVHD and cGVHD had no effect on overall survival (P = 0.159, 0.081). Non-remission status at allo-HCT was linked to lower overall survival (P = 0.001). CONCLUSION: The incidence of cGVHD was higher when male recipients received hematopoietic progenitor cells from female ≥30 years donors, and when older than 40 years recipients received hematopoietic progenitor cells from ≥30 years donors. Patients in non-remission status at allo-HCT was inclined to have lower overall survival.

4.
Chembiochem ; 2020 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-32189429

RESUMO

A novel immobilization of penicillin G acylase (PGA) with a lanthanum-incorporated mesostructured cellular foam (La-MCF) support has been developed utilizing the interaction between the strong Lewis acid sites on the surface of La-MCF and the free amino groups of lysine residues of PGA. The La-MCF support was successfully synthesized by the in situ synthesis method through the addition of a citric acid (CA) complexant. The results of pyridine-IR show the presence of strong Lewis acid sites on the surface of the prepared La-MCF (with CA), attributed to the incorporation of lanthanum species into the framework of MCF. Based on the interaction with the strong Lewis acid sites, the enzymes can be firmly immobilized on the surface of the support. The results indicate that the PGA/La-MCF (with CA) exibits a high specific activity and greatly enhancing operational stability. For the hydrolysis of penicillin G potassium salt, the initial specific activity of PGA/La-MCF (with CA) reaches 10023 U/g. After recycled for 10 times, PGA/La-MCF (with CA) retains 89% of its initial specific activity, much higher than 77% of PGA/Si-MCF.

5.
Exerc Sport Sci Rev ; 48(2): 74-82, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32168170

RESUMO

Hypothalamic pro-opiomelanocortin (POMC) neurons are key sensory neurons for energy balance. The basic helix-loop-helix transcription factor NHLH2 is expressed in POMC neurons, and Nhlh2 knockout mice show adult-onset obesity with low exercise behavior. Evidence is presented to explore the hypothesis that NHLH2 transcriptional activity within POMC neurons is crucial for maintaining motivated spontaneous activity and enforced exercise.

6.
Molecules ; 25(6)2020 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-32168821

RESUMO

Domino cyclization reactions of N-aryl-1,4- and 1,5-benzoxazepine derivatives involving [1,5]-hydride shift or C(sp2)-H functionalization were investigated. Neuroprotective and acetylcholinesterase activities of the products were studied. Domino Knoevenagel-[1,5]-hydride shift-cyclization reaction of N-aryl-1,4-benzoxazepine derivatives with 1,3-dicarbonyl reagents having active methylene group afforded the 1,2,8,9-tetrahydro-7bH-quinolino [1,2-d][1,4]benzoxazepine scaffold with different substitution pattern. The C(sp3)-H activation step of the tertiary amine moiety occurred with complete regioselectivity and the 6-endo cyclization took place in a complete diastereoselective manner. In two cases, the enantiomers of the chiral condensed new 1,4-benzoxazepine systems were separated by chiral HPLC, HPLC-ECD spectra were recorded, and absolute configurations were determined by time-dependent density functional theory- electronic circular dichroism (TDDFT-ECD) calculations. In contrast, the analogue reaction of the regioisomeric N-aryl-1,5-benzoxazepine derivative did not follow the above mechanism but instead the Knoevenagel intermediate reacted in an SEAr reaction [C(sp2)-H functionalization] resulting in a condensed acridane derivative. The AChE inhibitory assays of the new derivatives revealed that the acridane derivative had a 6.98 µM IC50 value.

7.
Stem Cell Res ; 43: 101704, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32014801

RESUMO

An induced pluripotent stem cell (iPSC) line was generated from peripheral blood mononuclear cells of a 3-day-old boy with 47,XXY and ornithine transcarbamylase deficiency carrying hemizygote mutation (c.663+2T>G (sliping)) in OTC. The iPSCs had original 47,XXY, and mutation in OTC, expressing pluripotency markers and bearing differentiation potential in vitro.

8.
Sensors (Basel) ; 20(3)2020 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-32023891

RESUMO

This paper describes an imaging method for near-field defect detection in aluminum plates based on Green's function recovery and application of instantaneous phase coherence weighting factors. The directly acquired acoustic information of near-field defects is usually obscured by the nonlinear effects due to the physical limitation of the acquisition system. Using the diffuse field to recover the Green's function can effectively retrieve the early time information. However, averaging operations of finite number in this process produces an imperfect imaging result. In order to improve the image quality, two kinds of instantaneous phased coherence weighting factors are used to weight the Green's function to reduce the background noise and improve the signal-to-noise ratio: the instantaneous phase coherence factor (IPCF), and the instantaneous phase weighting factor (IPWF). Experiments are conducted on two aluminum plates with two and four near-field defects, respectively. As a result, the background noise of amplitude images weighted by IPCF and IPWF is less than that of the conventional total focusing method (TFM). In addition, the IPCF image achieves a better signal-to-noise ratio (SNR) than that of IPWF, and the phase discontinuity in an IPWF image is suppressed through the IPCF.

9.
Artigo em Inglês | MEDLINE | ID: mdl-32017333

RESUMO

New, biocompatible materials with favorable antibacterial activity are highly desirable. In this work, we develop a unique conjugated polymer featuring aggregation-induced emission (AIE) for reliable bacterial eradication. Thanks to the AIE and donor-π-acceptor structure, this polymer shows a high reactive oxygen species (ROS)-generation ability compared to a low-mass model compound and the common photosensitizer Chlorin E6. Moreover, the selective binding of pathogenic microorganisms over mammalian cells was found, demonstrating its biocompatibility. The effective growth inhibition of bacteria upon polymer treatment under light irradiation was validated in vitro and in vivo. Notably, the recovery from infection after treatment with our polymer is faster than that with cefalotin. Thus, this polymer holds great promise in fighting against bacteria-related infections in practical applications.

10.
Nano Lett ; 20(3): 2034-2046, 2020 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-32019311

RESUMO

Tin-based composites hold promise as anodes for high-capacity lithium/sodium-ion batteries (LIBs/SIBs); however, it is necessary to use carbon coated nanosized tin to solve the issues related to large volume changes during electrochemical cycling, thus leading to the low volumetric capacity for tin-based composites due to their low packing density. Herein, we design a highly dense graphene-encapsulated nitrogen-doped carbon@Sn (HD N-C@Sn/G) compact monolith with Sn nanoparticles double-encapsulated by N-C and graphene, which exhibits a high density of 2.6 g cm-3 and a high conductivity of 212 S m-1. The as-obtained HD N-C@Sn/G monolith anode exhibits ultrahigh and durable volumetric lithium/sodium storage. Specifically, it delivers a high volumetric capacity of 2692 mAh cm-3 after 100 cycles at 0.1 A g-1 and an ultralong cycling stability exceeding 1500 cycles at 1.0 A g-1 with only 0.019% capacity decay per cycle in lithium-ion batteries. Besides, in situ TEM and ex situ SEM have revealed that the unique double-encapsulated structure effectively mitigates drastic volume variation of the tin nanoparticles during electrode cycling. Furthermore, the full cell using HD N-C@Sn/G as an anode and LiCoO2 as a cathode displays a superior cycling stability. This work provides a new avenue and deep insight into the design of high-volumetric-capacity alloy-based anodes with ultralong cycle life.

11.
New Phytol ; 2020 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-32083726

RESUMO

Systemin, a peptide plant hormone of 18 amino acids coordinates local and systemic immune responses. The activation of the canonical systemin-mediated systemic signaling pathway involves systemin release from its precursor prosystemin, systemin binding to its membrane receptor SYSTEMIN RECEPTOR1 (SYR1), and the transport of long-distance signaling molecules, including jasmonic acid, the prosystemin mRNA, volatile organic compounds and possibly systemin itself. Here, we review emerging evidence that the disordered structure and unconventional processing and secretion of systemin contribute to regulation of systemin-mediated signaling during plant defense. We highlight recent advances in systemin research, which elucidated how cells integrates multiple long-distance signals in the systemic defense response. In addition, we discuss the perception of systemin by SYR1 and its mediation of downstream defense responses.

12.
Stem Cell Res ; 43: 101709, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32058304

RESUMO

Methylmalonic acidemia and homocystinuria, cblC type is a rare autosomal recessive inheritance disease. Its clinical phenotype involves multiple systems with varying degrees of severity. The disease is caused by the mutations in the MMACHC gene located on chromosome 1p34.1. Here we report the generation of an iPSC line from the PBMCs of a patient with compound heterozygous mutations in the MMACHC gene. This new iPSC line will allow a better understanding of the MMA disease.

13.
Stem Cell Res ; 43: 101729, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32062132

RESUMO

Nemaline myopathy-2 (NEM2) is an autosomal recessive skeletal muscle disorder caused by mutations in the nebulin (NEB) gene. We report the generation and characterization of a human induced pluripotent stem cell (iPSC) line SDQLCHi017-A, derived from a 1-month-old patient with NEM2 carrying compound heterozygote mutations (c.6915+1G>T, c.14910+3G>C) in NEB gene. The peripheral blood mononuclear cells (PBMCs) were reprogrammed with non-integrating episomal vectors coding OCT4, SOX2, KLF4, BCL-XL and MYC. The established iPSC line contained the same mutations found in the patient, showed a normal karyotype, could differentiate into cells of three germ layers in vitro and expressed pluripotency markers.

14.
J Ethnopharmacol ; 253: 112658, 2020 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-32035876

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Many bioactive constituents of Chinese herbal medicines have poor oral bioavailability. Besides oral administration, herbal medicines in China are also prepared for parenteral administration. Unlike for intravenous route, little is known about the intramuscular pharmacokinetics of herbal compounds. To facilitate rational use of herbal medicine, it is important to better understand such intramuscular pharmacokinetics. AIM OF THE STUDY: Bioactive constituents of XueShuanTong (a lyophilized extract of Panax notoginseng roots, extensively used in treatment of ischemic heart and cerebrovascular diseases) predominantly comprise ginsenosides Rb1 and Rd of 20(S)-protopanaxadiol-type and ginsenosides Rg1, and Re, and notoginsenoside R1 of 20(S)-protopanaxatriol-type; these saponins are poorly absorbed from the gastrointestinal tract. This study aimed to compare intramuscular and intravenous pharmacokinetics of these ginsenosides after dosing XueShuanTong. METHODS: Pharmacokinetics of ginsenosides was assessed in human volunteers receiving an intramuscular injection or 1.5-h intravenous infusion of XueShuanTong, both at 150 mg/person, and the plasma and urine samples were analyzed by liquid chromatography/mass spectrometry. RESULTS: Like after intravenous administration, the unchanged saponins were the major circulating forms after intramuscular administration, while their metabolites were poorly detected. These ginsenosides exhibited intramuscular bioavailability of 100%-112%, relative to the respective intravenous data. Similar to that after intravenous infusion, the 20(S)-protopanaxadiol-type ginsenosides after the intramuscular injection exhibited notably longer terminal half-lives (46-106 h) than the 20(S)-protopanaxatriol-type ginsenosides (1.1-1.4 h). CONCLUSIONS: Intramuscular route might be an effective alternative to intravenous route for XueShuanTong, from the pharmacokinetic perspective.

15.
Photodiagnosis Photodyn Ther ; : 101696, 2020 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-32109616

RESUMO

BACKGROUND: Anal canal condylomata acuminata is a common male homosexually transmitted disease caused by the human papilloma virus. Conventional cauterizing laser treatment cannot achieve a satisfactory result owing to a high recurrence rate, and the application of 5-aminolaevulinic acid-photodynamic therapy (ALA-PDT) also has limitations in the anal canal. Holmium yttrium aluminum garnet (Ho: YAG) laser with fiber is found to be effective at removing canal lesions, and may create suitable conditions for ALA-PDT. We aim to investigate the feasibility of Ho: YAG laser combined with ALA-PDT and to explore a more optimal therapy in refractory anal canal condylomata. METHODS: Data of 37 patients with anal canal condylomata (number of warts≥ 10 lesions) from May 2017 to March 2019 were reviewed. In total 17 cases were treated with Ho: YAG laser plus ALA-PDT, and 20 patients treated with CO2 laser plus ALA-PDT were selected as control. Wart clearance and recurrence rates were evaluated as well as laser complications. RESULTS: Most warts (88.23%) were removed after a session of Ho: YAG laser pretreatment. The average number of laser sessions required to clear all warts was 1.94 in the Ho: YAG laser plus ALA-PDT group, which was obviously decreasing treatment duration. Meanwhile, no wound infections or defecation disfunctions were found. Ho: YAG laser with ALA-PDT could significantly reduce wart recurrence rates (17.6%) in comparison with CO2 laser with ALA-PDT (55%). CONCLUSIONS: Ho: YAG laser combined with ALA-PDT raised the cure rate of refractory anal canal condylomata and has important guidance implications for clinical application.

16.
Cell Death Dis ; 11(1): 17, 2020 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-31907348

RESUMO

Endoplasmic reticulum (ER) stress-associated cell death is prevalent in various liver diseases. However, the determinant mechanism how hepatocytes survive unresolved stress was still unclear. Interleukin-24 (IL-24) was previously found to promote ER stress-mediated cell death, and yet its expression and function in the liver remained elusive. Here we identified an antiapoptotic role of IL-24, which transiently accumulated within ER-stressed hepatocytes in a X-box binding protein 1 (XBP1)-dependent manner. Disruption of IL-24 increased cell death in the CCL4- or APAP-challenged mouse liver or Tm-treated hepatocytes. In contrast, pharmaceutical blockade of eukaryotic initiation factor 2α (eIF2α) or genetical ablation of C/EBP homologous protein (CHOP) restored hepatocyte function in the absence of IL-24. In a clinical setting, patients with acute liver failure manifested a profound decrease of hepatic IL-24 expression, which was associated with disease progression. In conclusion, intrinsic hepatocyte IL-24 maintains ER homeostasis by restricting the eIF2α-CHOP pathway-mediated stress signal, which might be exploited as a bio-index for prognosis or therapeutic intervention in patients with liver injury.

17.
Aging (Albany NY) ; 12(2): 1087-1103, 2020 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-31945013

RESUMO

BACKGROUND: It is generally thought that the occurrence and progression of osteoarthritis (OA) results from multiple causes, including degradation and destruction of the cartilage matrix and aging of chondrocytes. Metformin is a first-line drug for the treatment of diabetes, and has great potential for the treatment of other disorders. However, the role of metformin in OA is unknown. RESULTS: Metformin displayed a protective effect against OA. There were lower OARSI scores and fewer MMP-13-positive cells in DMM mice and cartilage explants after treatment with metformin. In addition, metformin treatment decreased p16INK4a levels in OA chondrocytes, and enhanced polarization of AMPK and inhibition of mTORC1 in OA mice and chondrocytes in a dose-dependent manner. CONCLUSIONS: Metformin effectively alleviated cartilage degradation and aging through regulation of the AMPK/mTOR signaling pathways, suggesting that it could be an effective treatment for OA. METHODS: The effects of metformin on cartilage degradation and chondrocyte aging was determined in a destabilization of the medial meniscus (DMM)-induced OA mouse model and in IL-1ß-treated mouse chondrocytes and cartilage explants. Articular cartilage degeneration was graded using the Osteoarthritis Research Society International (OARSI) criteria. Immunostaining, RT-PCR, and western blot analyses were conducted to detect the relative expressions of protein and RNA.

18.
Exerc Sport Sci Rev ; 2020 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-32000179

RESUMO

Hypothalamic pro-opiomelanocortin (POMC) neurons are key sensory neurons for energy balance. The basic helix-loop helix transcription factor, NHLH2 is expressed in POMC neurons, and Nhlh2 knockout mice show adult-onset obesity with low exercise behavior. Evidence is presented to explore the hypothesis that NHLH2 transcriptional activity within POMC neurons is crucial for maintaining motivated spontaneous activity and enforced exercise.

19.
Biosci Biotechnol Biochem ; : 1-9, 2020 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-31985358

RESUMO

Previous RNA-Seq analyses revealed that NAD(P)H steroid dehydrogenase-like (NSDHL) has a different expression during 3T3-L1 differentiation; however, its roles in adipogenesis are unknown. In the present study, using quantitative real-time PCR, we confirmed that NSDHL knockdown increased the proliferation of 3T3-L1 preadipocytes, but attenuated the differentiation of 3T3-L1 preadipocytes, as evidenced by reduced lipid accumulation and down-regulation of PPARγ gene expression. Further analyses showed that the expression peak of NSDHL was at the early stage of 3T3-L1 preadipocytes differentiation and LXR-SREBP1 signaling pathway was downregulated in NSDHL-knockdown 3T3-L1 cells. Collectively, our findings indicate that NSDHL is a novel modulator of adipogenesis. Moreover, our data provide insight into the complex relationships between sterol sensing, LXR-SREBP1 signaling pathway, and PPARγ in 3T3-L1 cells.

20.
Blood Purif ; : 1-8, 2020 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-31927549

RESUMO

INTRODUCTION: Ultrasound-guided thoracic paravertebral block (US-TPVB) is generally used for postoperative analgesia. We hypothesized that single-injection US-TPVB could be used as the principal anesthetic technique for a peritoneal dialysis catheter (PDC) procedure (implantation or removal). The anesthetic effect and venous ropivacaine level after a TPVB would be compared with that after local anesthetic infiltration (LAI). METHODS: Patients undergoing PDC procedures were randomized into Group LAI or TPVB. In Group LAI, 40 mL of 0.25% ropivacaine were used. In Group TPVB, single-injection of US-TPVB at T10-T11 level was performed with 20 mL of 0.25% ropivacaine. The quality of anesthesia, visual analogue scale of pain, and venous total plasma ropivacaine level were compared between the 2 groups. RESULTS: Seventy-four eligible patients were enrolled and 38 in Group TPVB. Thirty patients in Group TPVB and 26 patients in Group LAI underwent PDC procedures successfully. Higher satisfaction rates by nephrologists and patients (76.3 and 78.9%) were reported in Group TPVB (44.4 and 44.4% in Group LAI, respectively). The peak venous total plasma ropivacaine concentrations were below the reported toxic threshold in the 2 groups. CONCLUSIONS: A single-injection US-TPVB with 20 mL of 0.25% ropivacaine at T10-T11 could be the principal anesthetic technique for PDC procedures, which provided a comparable anesthetic effect to that of LAI with 40 mL ropivacaine. Higher satisfaction rates by nephrologists and patients were observed in Group TPVB. The 20 mL dose of 0.25% ropivacaine used for an US-TPVB was safe in end-stage renal diseases patients.

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