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1.
Artigo em Inglês | MEDLINE | ID: mdl-32043798

RESUMO

BACKGROUND: Tissue factor pathway inhibitor 2 (TFPI-2) has been recently identified as a tumor suppressor gene in several human cancers, whereas its role in thyroid cancer has been unclear. METHODS: The TFPI-2 protein level in thyroid cancer tissues and cell lines (8305C and B-CPAP) were examined using immunohistochemistry and immunoblotting. The TFPI-2 promoter methylation was examined using methylation-specific polymerase chain reaction (MSP). Lentivirus containing TFPI-2 cDNA (Lenti-TFPI-2) was constructed to elevate TFPI-2 expression in 8305C and B-CPAP cells. The effects of Lenti-TFPI-2 on cell proliferation in vitro and in vivo were evaluated by MTT assay and mouse xenograft model. Annexin V/PI double staining assay was performed to detect the effect of Lenti-TFPI-2 on cell apoptosis. RESULTS: TFPI-2 protein level were decreased in cancer tissues and lymph node metastasis, and TFPI-2 protein level is positively associated with survival time. The promoter of TFPI-2 is hypermethylated in cancer tissues. TFPI-2 mRNA and protein levels were abundant in normal human thyroid follicular cell line Nthy-ori 3-1 cells, whereas they were decreased in 8305C and B-CPAP cells. pcDNA-TFPI-2 elevated TFPI-2 mRNA and protein in 8305C and B-CPAP cells. TFPI-2 overexpression suppressed proliferation and induced apoptosis of 8305C and B-CPAP cells. CONCLUSIONS: TFPI-2 inactivation may play a role in thyroid cancer tumorigenesis and development. TFPI-2 overexpression suppressed cell proliferation through induction of cell apoptosis, suggesting that TFPI-2 may serve as a novel and effective target for thyroid cancer therapy.

2.
Echocardiography ; 2020 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-32045034

RESUMO

Coronary artery fistula (CAF) is a congenital disease in which a communication forms between one or more coronary arteries and a cardiac chamber or great vessel. We describe an infrequent case of right coronary artery (RCA) fistula into the right ventricle (RV) complicated by infective endocarditis in a child. The patient received echocardiography and contrast-enhanced multidetector computed tomography (MDCT). Surgical treatment was performed after management of the infection. Unfortunately, a residual fistula formed after surgery. However, interestingly, the residual fistula spontaneously resolved at one year after surgery. He is now in good condition and totally asymptomatic.

3.
BMC Oral Health ; 20(1): 27, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-32000757

RESUMO

BACKGROUND: Both substance P and hypoxia-inducible factor 1 alpha (HIF-1α) are involved in inflammation and angiogenesis. However, the relationship between substance P and HIF-1α in rat periodontitis is still unknown. METHODS: Ligation-induced rat periodontitis was established to observe the distribution and expression of substance P and HIF-1α by immunohistochemistry. Rat gingival fibroblasts were cultured and stimulated with Porphyromonas gingivalis lipopolysaccharide (LPS). Recombinant substance P was applied to elaborate the relationship between substance P and HIF-1α in gingival fibroblasts in vitro. Primary mouse bone marrow-derived macrophages (BMMs) were isolated and cultured to observe the effect of substance P on receptor activator of NF-κB ligand (RANKL)-induced osteoclastogenesis by TRAP staining. Western blotting was used to investigate the expression of HIF-1α, osteoprotegerin (OPG) and RANKL. RESULTS: Rat experimental periodontitis was successfully established 6 weeks after ligation. Gingival inflammatory infiltration and alveolar bone loss were observed. Positive expression of substance P was found in the infiltrating cells. Higher HIF-1α levels were observed in periodontitis compared to that of normal tissues. Substance P upregulated the level of HIF-1α in gingival fibroblasts with or without 1 µg/ml LPS in vitro (*P < 0.05). Substance P upregulated the expression of HIF-1α in RANKL-stimulated BMMs in vitro. Substance P also increased the RANKL/OPG ratio in gingival fibroblasts (*P < 0.05). Both 10 nM and 50 nM substance P promoted RANKL-induced osteoclast differentiation (*P < 0.05). CONCLUSION: Substance P participates in periodontitis by upregulating HIF-1α and the RANKL/OPG ratio.

4.
Metallomics ; 2020 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-32039426

RESUMO

Selenium (Se) is an essential trace element that has several functions in cellular processes related to cancer prevention. While the cancericidal effect of Se has been reported in liver cancer, the mechanism has not been clarified. MiR-29a has widely been reported as a tumor suppressor; however, it also acts as a carcinogenic agent by increasing cell invasion in human epithelial cancer cells and hepatoma cells. In a previous study, we found that miR-29a-3p is a Se-sensitive miRNA. However, its effect in the chicken hepatocellular carcinoma cell line (LMH) is still unknown. In the present study, we found that the expression of miR-29a-3p in LMH cells was decreased by Se supplementation and increased under Se-deficient conditions. Flow cytometry and CCK-8 results suggested that Se decreased LMH cell proliferation induced by miR-29a-3p overexpression. Transwell and gap-closure assays implied that Se mediated LMH cell invasion and migration by downregulating miR-29a-3p. Quantitative real-time polymerase chain reaction and Western blotting results suggested that Se mitigated miR-29a-3p overexpression-induced LMH cell proliferation by downregulating CDK2, cyclin-D1, CDK6, and cyclin-E1. We further demonstrated that collagen type IV alpha 2 (COL4A2) is a target gene of miR-29a-3p. COL4A2 activates the RhoA/ROCK pathway to promote LMH cell invasion and migration. In conclusion, Se mediated miR-29a-3p overexpression induced LMH cell invasion and migration by targeting COL4A2 to inactivate the RhoA/ROCK pathway.

5.
Pharmacol Rep ; 72(1): 208-213, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32016842

RESUMO

BACKGROUND: αB-crystallin (CRYAB) is a small heat shock protein that is able to inhibit neuroinflammatory responses under various pathological conditions. Some studies have proven that neuroinflammatory mechanisms play important roles in bone cancer pain (BCP). However, whether CRYAB participates in the maintenance of BCP has not yet been examined. METHODS: Walker256 tumour cells were inoculated into the tibia to induce a rat model of BCP. Von Frey hairs were used to measure mechanical allodynia. Immunohistochemistry and western blotting were used to examine the expression level of CRYAB in the spinal dorsal horn. RESULTS: The gradual development of mechanical allodynia was induced by the injection of Walker256 cells into the tibia. The downregulation of spinal CRYAB expression was found in BCP rats. The intrathecal administration of CRYAB (from days 9 to 15 post-inoculation) dose-dependently alleviated mechanical allodynia in BCP rats. Additionally, there were concomitant increases in spinal CRYAB expression and decreases in TNF-α expression. CONCLUSIONS: Spinal CRYAB may participate in the maintenance of BCP in rats. The findings will help to identify new drugs for the management of BCP.

6.
J Neuroinflammation ; 17(1): 51, 2020 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-32028989

RESUMO

BACKGROUND: Radiotherapy is widely used and effective for treating brain tumours, but inevitably impairs cognition as it arrests cellular processes important for learning and memory. This is particularly evident in the aged brain with limited regenerative capacity, where radiation produces irreparable neuronal damage and activation of neighbouring microglia. The latter is responsible for increased neuronal death and contributes to cognitive decline after treatment. To date, there are few effective means to prevent cognitive deficits after radiotherapy. METHODS: Here we implanted hematopoietic stem cells (HSCs) from young or old (2- or 18-month-old, respectively) donor mice expressing green fluorescent protein (GFP) into old recipients and assessed cognitive abilities 3 months post-reconstitution. RESULTS: Regardless of donor age, GFP+ cells homed to the brain of old recipients and expressed the macrophage/microglial marker, Iba1. However, only young cells attenuated deficits in novel object recognition and spatial memory and learning in old mice post-irradiation. Mechanistically, old recipients that received young HSCs, but not old, displayed significantly greater dendritic spine density and long-term potentiation (LTP) in CA1 neurons of the hippocampus. Lastly, we found that GFP+/Iba1+ cells from young and old donors were differentially polarized to an anti- and pro-inflammatory phenotype and produced neuroprotective factors and reactive nitrogen species in vivo, respectively. CONCLUSION: Our results suggest aged peripherally derived microglia-like cells may exacerbate cognitive impairments after radiotherapy, whereas young microglia-like cells are polarized to a reparative phenotype in the irradiated brain, particularly in neural circuits associated with rewards, learning, and memory. These findings present a proof-of-principle for effectively reinstating central cognitive function of irradiated brains with peripheral stem cells from young donor bone marrow.

7.
BMJ Open ; 10(2): e034003, 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-32029493

RESUMO

INTRODUCTION: Scalp nerve block has been proven to be an alternative choice to opioids in multimodal analgesia. However, for the infratentorial space-occupying craniotomy, especially the suboccipital retrosigmoid craniotomy, scalp nerve block is insufficient. METHODS AND ANALYSIS: The study is a prospective, single-centre, randomised, paralleled-group controlled trial. Patients scheduled to receive elective suboccipital retrosigmoid craniotomy will be randomly assigned to the superficial cervical plexus block group or the control group. After anaesthesia induction, superficial cervical plexus nerve block will be performed under the guidance of ultrasound. The primary outcome is the cumulative consumption of sufentanil by the patient-controlled intravenous analgesia pump within 24 hours after surgery. Secondary outcomes include the cumulative consumption of sufentanil at other four time points and numerical rating scale pain severity score. ETHICS AND DISSEMINATION: The protocol (version number: 2.0, 10 April 2019) has been approved by the Ethics Review Committee of China Registered Clinical Trials (Ethics Review No. ChiECRCT-20190047). The findings of this study will be disseminated in peer-reviewed journals and at scientific conferences. TRIAL REGISTRATION NUMBER: NCT04036812.

8.
Mol Cell Endocrinol ; : 110742, 2020 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-32006608

RESUMO

Epidemiological evidence suggests that the etiology and pathogenesis of rheumatoid arthritis (RA) are closely associated with estrogen metabolism and deficiency. Estrogen protects against articular damage. Estradiol replacement therapy ameliorates local inflammation and knee joint swelling in ovariectomized models of RA. The mechanistic basis for the protective role of 17ß-estradiol (17ß-E2) is poorly understood. Acid-sensing ion channel 1a (ASIC1a), a sodium-permeable channel, plays a pivotal role in acid-induced articular chondrocyte injury. The aims of this study were to evaluate the role of 17ß-E2 in acid-induced chondrocyte injury and to determine the effect of 17ß-E2 on the level and activity of ASIC1a protein. Results showed that pretreatment with 17ß-E2 attenuated acid-induced damage, suppressed apoptosis, and restored mitochondrial function. Further, 17ß-E2 was shown to reduce protein levels of ASIC1a through the autophagy-lysosomal pathway, to protect chondrocytes from acid-induced apoptosis, and to induce ASIC1a protein degradation through the ERα receptor. Taken together, these results show that the use of 17ß-E2 may be a novel strategy for the treatment of RA by reducing cartilage destruction through down-regulation of ASIC1a protein levels.

9.
Aging Cell ; : e13103, 2020 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-31960578

RESUMO

Extracellular vesicles (EVs) have emerged as important regulators of inter-cellular and inter-organ communication, in part via the transfer of their cargo to recipient cells. Although circulating EVs have been previously studied as biomarkers of aging, how circulating EVs change with age and the underlying mechanisms that contribute to these changes are poorly understood. Here, we demonstrate that aging has a profound effect on the circulating EV pool, as evidenced by changes in concentration, size, and cargo. Aging also alters particle function; treatment of cells with EV fractions isolated from old plasma reduces macrophage responses to lipopolysaccharide, increases phagocytosis, and reduces endothelial cell responses to vascular endothelial growth factor compared to cells treated with young EV fractions. Depletion studies indicate that CD63+ particles mediate these effects. Treatment of macrophages with EV-like particles revealed that old particles increased the expression of EV miRNAs in recipient cells. Transfection of cells with microRNA mimics recapitulated some of the effects seen with old EV-like particles. Investigation into the underlying mechanisms using bone marrow transplant studies revealed circulating cell age does not substantially affect the expression of aging-associated circulating EV miRNAs in old mice. Instead, we show that cellular senescence contributes to changes in particle cargo and function. Notably, senolytic treatment of old mice shifted plasma particle cargo and function toward that of a younger phenotype. Collectively, these results demonstrate that senescent cells contribute to changes in plasma EVs with age and suggest a new mechanism by which senescent cells can affect cellular functions throughout the body.

10.
Artigo em Inglês | MEDLINE | ID: mdl-31989220

RESUMO

Cyclodipeptide oxidases (CDOs) perform dehydrogenations on diketopiperazines and play an important role in the cyclodipeptide diversification. In this study, we investigated the two known CDOs AlbA/B and Ndas_1146/7 and one new member, CDO-Np. LC-MS monitoring of 32 cyclodipeptide biotransformations in E. coli revealed good consumption of cyclodipeptides containing aromatic amino acids. Cyclodipeptides consisting solely of aliphatic amino acids were poor substrates. In vitro assays of 34 substrates with crude enzyme extracts and product identification proved that the CDO-Np-containing extract catalyzes the formation of two C-C double bonds in many cases. The extracts containing the two other enzymes had lower activities and catalyzed mainly didehydrogenations. For didehydrogenation, the phenylalanyl or tyrosyl site was usually preferred. No or very low acceptance of benzodiazepinediones and a 2,6-diketopiperazine proved the importance of the 2,5-diketopiperazine ring. N-Methylation at the diketopiperazine ring or prenylation of the tryptophan-containing cyclodipeptides influences the enzyme activity and product spectrum. KEY POINTS: • Comparison of catalytic activities of three enzymes; Diverse cyclodipeptides and derivatives as substrates; Determination of double bond formation using2H-labeled substrates; Product identification also by interpretation of MS2fragmentation pattern.

11.
J Control Release ; 320: 73-82, 2020 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-31958479

RESUMO

Cardiac tissue engineering is of particular importance in the combination of contracting cells with a biomaterial scaffold, which serves as a cell-delivery construct, to replace cardiomyocytes (CMs) that are lost as a result of an infarction, to restore heart function. However, most biomaterial scaffolds are nonconductive and may delay regional conduction, potentially causing arrhythmias. In this study, a conductive CM-delivery construct that consists of a gelatin-based gelfoam that is conjugated with a self-doped conductive polymer (poly-3-amino-4-methoxybenzoic acid, PAMB) is proposed as a cardiac patch (PAMB-Gel patch) to repair an infarcted heart. A nonconductive plain gelfoam (Gel patch) is used as a control. The electrical conductivity of the PAMB-Gel patch is approximately 30 times higher than that of the Gel patch; as a result, the conductive PAMB-Gel patch can substantially increase electrical conduction between distinct clusters of beating CMs, facilitating their synchronous contraction. In vivo epicardial implantation of the PAMB-Gel patch that is seeded with CMs (the bioengineered patch) in infarcted rat hearts can significantly enhance electrical activity in the fibrotic tissue, improving electrical impulse propagation and synchronizing CM contraction across the scar region, markedly reducing its susceptibility to cardiac arrhythmias. Echocardiography shows that the bioengineered conductive patch has an important role in the restoration of cardiac function, perhaps owing to the synergistic effects of its conductive construct and the synchronously beating CMs. These experimental results reveal that the as-proposed bioengineered conductive patch has great potential for repairing injured cardiac tissues.

12.
Food Funct ; 11(1): 640-648, 2020 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-31895399

RESUMO

Aspergillus oryzae is a common starter in the soy sauce industry and struggles to grow under complex fermentation conditions. However, little is known about the flavor formation mechanism under osmotic conditions (low-temperature and high-salt) in A. oryzae. This work investigated the flavors and the relative protein expression patterns by gas chromatography-mass spectrometry (GC-MS) and proteomic analysis. Low-temperature and a high-salt content are unfavorable to the secretion of hydrolases and the formation of fragrant aldehydes. The aldehyde contents under osmotic conditions were reduced to 1.4-3.7 times lower than that of the control. Besides, copper amine oxidases which decreased under low-temperature stress and salt stress were shown to be important in catalyzing the oxidative deamination of several amine substrates to fragrant aldehydes. Furthermore, alcohol dehydrogenase and polyketide synthase are beneficial to the formation of alcohols and aromatic flavors under low-temperature stress and salt stress. Particularly, the ethanol content under 16 °C stress was 3.5 times higher than that under 28 °C.

13.
Artigo em Inglês | MEDLINE | ID: mdl-31999502

RESUMO

Background: Nonobese individuals with disproportionate body fat distribution are also vulnerable to dysglycemia. This study aimed to evaluate the association between three visceral adiposity surrogates and impaired fasting glucose (IFG) in nonobese Chinese individuals. Methods: A total of 70,200 nonobese adults without diabetes were included in this analysis. Two diagnostic criteria (IFG-ADA and IFG-WHO) were used to define IFG. The values of the visceral adiposity index, lipid accumulation product index (LAP), and cardiometabolic index (CMI) were calculated. Multivariable logistic analysis was used to evaluate the association between these surrogates and IFG. Results: Among the three indicators, only LAP and CMI were positively correlated with fasting plasma glucose (all P < 0.001). After fully adjusting for confounders, only LAP and CMI exhibited significant associations with IFG. For women, the odds ratios (ORs) for IFG-ADA in the highest quartile of the LAP and CMI were 1.967 (95% confidence interval [CI]: 1.645-2.353) and 1.594 (95% CI: 1.383-1.836), respectively; and were 2.025 (95% CI: 1.597-2.567) and 2.017 (95% CI: 1.647-2.470), respectively, for IFG-WHO (all P < 0.001). For men, the ORs for IFG-ADA of the LAP and CMI were 1.503 (95% CI: 1.233-1.833) and 2.045 (95% CI: 1.752-2.388), respectively; and were 1.534 (95% CI: 1.174-2.005) and 2.541 (95% CI: 2.025-3.188), respectively, for IFG-WHO (all P < 0.001). Conclusions: The LAP and CMI, cost-effective and simple visceral adiposity surrogates, are strongly associated with IFG in nonobese Chinese individuals. These surrogates might be potential targets to monitor for the recognition and management of excess visceral adiposity in nonobese individuals with prediabetes.

14.
Am J Pathol ; 2020 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-31954697

RESUMO

Hepatocellular carcinoma (HCC) ranks as the fifth most common cancer worldwide, and it is the primary histologic subtype of liver cancer, with high incidence and poor prognosis. Recently, numerous long noncoding RNAs have been reported to be associated with the tumorigenesis of HCC; however, the underlying mechanisms of long intergenic nonprotein coding RNA 0152 (LINC00152) action in HCC are poorly understood. Herein, we identified a significant up-regulation of LINC00152 in both HCC tissues and cell lines. Functional studies showed that knockdown of LINC00152 inhibited cell proliferation, migration, and invasion, but promoted cell apoptosis, indicating its oncogenic functions in HCC tumorigenesis. Mechanistically, LINC00152 functioned as an efficient miR-139 sponge, thereby releasing the suppression of PIK3CA (a target gene of miR-139). Anti-miR-139 rescued the inhibition of cell proliferation, migration, and invasion induced by LINC00152 knockdown. Similarly, PIK3CA-overexpressing plasmid also reversed miR-139-mediated biological functions in HCC cells. Taken together, our study revealed a crucial regulatory network of LINC00152/miR-139/PIK3CA axis in the tumorigenesis of HCC, implying that LINC00152 may be a biomarker and novel therapeutic target for further clinical therapy of HCC.

15.
J Biol Chem ; 2020 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-31949049

RESUMO

Insulin secretion by pancreatic islet ß-cells is regulated by glucose levels and is accompanied by proton generation. The voltage-gated proton channel Hv1 is present in pancreatic ß-cells and extremely selective for protons. However, whether Hv1 is involved in insulin secretion is unclear. Here, we demonstrate that Hv1 promotes insulin secretion of pancreatic ß-cells and glucose homeostasis. Hv1-deficient mice displayed hyperglycemia and glucose intolerance due to reduced insulin secretion, but retained normal peripheral insulin sensitivity. Moreover, Hv1 loss contributed much more to severe glucose intolerance as the mice got older. The islets of Hv1-deficient and heterozygous mice were markedly deficient in glucose- and K+-induced insulin secretion. In perifusion assays, Hv1 deletion dramatically reduced both the first and second phase of glucose-stimulated insulin secretion (GSIS). Islet insulin and proinsulin contents were reduced, and histological analysis of pancreas slices revealed an accompanying modest reduction of ß-cell mass in the Hv1-knockout mice. EM observations also indicated a reduction in insulin granule size, but not granule number or granule docking, in the Hv1-deficient mice. Mechanistically, Hv1 loss limited the capacity of glucose-induced membrane depolarization, accompanying the reduced ability of glucose to raise Ca2+ levels in islets, evidenced by a decreased duration of individual calcium oscillations. Moreover, Hv1 expression was significantly reduced in pancreatic ß-cells from streptozotocin-induced diabetic mice, indicating that Hv1 deficiency is associated with ß-cell dysfunction and diabetes. We conclude that Hv1 regulates insulin secretion and glucose homeostasis through a mechanism that depends on intracellular Ca2+ levels and membrane depolarization.

16.
Artigo em Inglês | MEDLINE | ID: mdl-31956937

RESUMO

Liquiritin (LIQ), a major constituent of Glycyrrhiza Radix, exhibits various pharmacological activities. In this study, to explore the potential anti-cancer effects and its underlying molecular mechanisms of LIQ in hepatocellular carcinoma (HCC) cells. LIQ significantly decreased viability and induced apoptosis in HepG2 cells by decreasing mitochondrial membrane potential and regulating Bcl-2 family proteins, cytochrome c, cle-caspase-3, and cle-PARP. The cell cycle analysis and western blot analysis revealed that LIQ induced G2/M phase arrest through increased expression of p21 and decreased levels of p27, cyclin B, and CDK1/2. The flow cytometry and western blot analysis also suggested that LIQ promoted the accumulation of ROS in HepG2 cells and up-regulated the phosphorylation expression levels of p38 kinase, c-Jun N-terminal kinase (JNK), and inhibitor of NF-κB (IκB-α); the phosphorylation levels of extracellular signal-regulated kinase (ERK), protein kinase B (AKT), signal transducer activator of transcription 3 (STAT3), and nuclear factor kappa B (NF-κB) were down-regulated. However, these effects were reversed by N-acetyl-L-cysteine (NAC), MAPK, and AKT inhibitors. The findings demonstrated that LIQ induced cell cycle arrest and apoptosis via the ROS-mediated MAPK/AKT/NF-κB signaling pathway in HepG2 cells, and the LIQ may serve as a potential therapeutic agent for the treatment of human HCC.

17.
Ying Yong Sheng Tai Xue Bao ; 31(1): 326-332, 2020 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-31957411

RESUMO

The phosphate-solubilizing medium plate screening and heavy metal resistance rescreening were used to isolate a phosphate-solubilizing bacterium (coded ZLT11) from the rhizosphere of Mikania micrantha. Results from 16S rRNA gene sequence analysis revealed that the strain ZLT11 belonged to Paenibacillus sp. The amount of phosphorus solubilized from calcium phytate and phytic acid by the ZLT11 was 84.10 and 73.84 mg·L-1, respectively. The maximum phosphate solubilizing activity to calcium phytate (95.66 mg·L-1) was at 30 ℃ and initial pH 9.0. The strain ZLT11 displayed the tolerance to ≤ 400 mg·L-1 Pb 2+, ≤ 100 mg·L-1 Cd 2+, and ≤ 40 mg·L-1 Hg 2+. With calcium phytate as phosphorus source, the inoculation strain ZLT11 treatment increased the average root length, root number, seedling height and total biomass of rice seedlings by 106.7%, 76.6%, 49.0% and 46.3%, respectively. The strain ZLT11 could improve rice seedlings growth under Cd stress.


Assuntos
Oryza , Paenibacillus , Fosfatos , Ácido Fítico , RNA Ribossômico 16S , Rizosfera , Microbiologia do Solo
18.
Nutrients ; 12(1)2020 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-31968655

RESUMO

Non-alcoholic fatty liver disease (NAFLD), the leading cause of chronic liver diseases worldwide, ranges from simple steatosis to steatohepatitis, with the risk for progressive fibrosis or even cirrhosis. While simple steatosis is a relatively benign condition, the buildup of toxic lipid metabolites can induce chronic inflammation, ultimately triggering disease progression. Pigment epithelium-derived factor (PEDF) is a secreted, multifunctional glycoprotein with lipid metabolic activities. PEDF promotes lipolysis through binding to adipose triglyceride lipase (ATGL), a key enzyme for triglyceride breakdown. In the current study, we aimed to delineate how changes in PEDF expression affect hepatic lipid accumulation. Our data revealed that hepatic PEDF was downregulated in a mouse NAFLD model. We further showed that decreased PEDF levels in hepatocytes in vitro resulted in elevated fatty acid uptake and lipid droplet formation, with concomitant upregulation of fatty acid transport proteins CD36 and fatty acid binding protein 1 (FABP1). RNA sequencing analysis of PEDF knocked down hepatocytes revealed an alteration in gene expression profile toward lipid accumulation. Additionally, decreased PEDF promotes mobilization of fatty acids, an observation distinct from blocking ATGL activity. Taken together, our data suggest that hepatic PEDF downregulation causes molecular changes that favor triglyceride accumulation, which may further lead to NAFLD progression.

19.
Int J Mol Sci ; 21(3)2020 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-31973163

RESUMO

The transfer of genetic material from the mitochondria and plastid to the nucleus gives rise to nuclear integrants of mitochondrial DNA (NUMTs) and nuclear integrants of plastid DNA (NUPTs). This frequently occurring DNA transfer is ongoing and has important evolutionary implications. In this review, based on previous studies and the analysis of NUMT/NUPT insertions of more than 200 sequenced plant genomes, we analyzed and summarized the general features of NUMTs/NUPTs and highlighted the genetic consequence of organellar DNA insertions. The statistics of organellar DNA integrants among various plant genomes revealed that organellar DNA-derived sequence content is positively correlated with the nuclear genome size. After integration, the nuclear organellar DNA could undergo different fates, including elimination, mutation, rearrangement, fragmentation, and proliferation. The integrated organellar DNAs play important roles in increasing genetic diversity, promoting gene and genome evolution, and are involved in sex chromosome evolution in dioecious plants. The integrating mechanisms, involving non-homologous end joining at double-strand breaks were also discussed.

20.
Chemosphere ; 246: 125820, 2020 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-31918111

RESUMO

[Background] Melamine and phthalates have been reported to damage renal function in children. This association is scarce in general adults. [Method] A cross-sectional subsample population of 611 adults participating in the 2012 Shanghai Food Consumption Survey (SHFCS) was analyzed for urinary biomarkers of melamine, metabolites of phthalates, and renal function parameters. The correlations between renal function parameters and chemical exposure (either independently or interactively) were explored by linear regression models. To simplify the analysis, phthalate metabolites were dimensionally reduced using principal component analysis (PCA) method. [Result] Urinary melamine was positively associated with renal function parameters of both albumin-to-creatinine ratio (ACR) and ß2-microglobulin (B2M) in multivariate linear regression models (P < 0.05). A PCA pattern characterized by high-molecular-weight phthalates (HMWP) was positively associated with all three parameters of renal function (ACR, B2M, and N-acetyl-ß-d-glucosaminidase (NAG)). The co-exposure to melamine and HMWP presented an additive effect on increasing these parameters (ACR, B2M, and NAG). [Conclusion] Impaired renal function in Shanghai adults was associated with exposure to both melamine and HMWP.

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