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1.
J Ethnopharmacol ; 282: 114582, 2022 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-34492322

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Due to the modernization of traditional Chinese medicine (TCM) and the influence of traditional medication habits (TCM has no toxicity or side effects), arsenic poisoning incidents caused by the abuse of realgar and realgar-containing Chinese patent medicines have occurred occasionally. However, the potential mechanism of central nervous system toxicity of realgar remains unclear. AIM OF THE STUDY: This study aimed to clarify the specific mechanism of realgar-induced neurotoxicity. MATERIALS AND METHODS: In this study, the roles of ERK1/2 and p38 MAPK in realgar-induced neuronal autophagy and overactivation of the nuclear factor erythroid-derived factor 2-related factor (Nrf2) signalling pathways was investigated in vivo and in vitro. RESULTS: The arsenic in realgar passed through the blood-brain barrier and accumulated in the brain, resulting in damage to neurons, synapses and myelin sheaths in the cerebral cortex and a decrease in the total antioxidant capacity. The specific mechanism is that the excessive activation of Nrf2 is regulated by the upstream signalling molecules ERK1/2 and p38MAPK. At the same time, p38 MAPK and ERK1/2 interfere with autophagy, thereby promoting autophagy initiation but causing subsequent dysfunctional autophagic degradation and inducing the p62-Keap1-Nrf2 feedback loop to promote Nrf2 signalling pathway activation and nerve cell apoptosis. CONCLUSIONS: This study confirmed the role of the signalling molecules p38 MAPK and ERK1/2 in perturbing autophagy and inducing the p62-Keap1-Nrf2 feedback loop to activate the Nrf2 signalling pathway in realgar-induced neurotoxicity.

2.
Chemosphere ; 286(Pt 3): 131758, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34399255

RESUMO

Wasted polyethylene (PE) products caused pollution has become a global issue. Researchers have identified PE-degrading bacteria which have been considered as a sustainable alleviation to this crisis. However, the degradation mechanism employed by currently isolated bacteria is unclear and their degradation efficiencies are insufficient. More importantly, there is little research into bacteria capable of degrading PE mulching film to solve "white" pollution in agriculture. We determined the PE degradation efficiency of two Pseudomonas, identified by 16S rDNA analysis, and elucidated their potential mechanisms through whole genome sequencing. During an 8-week period, PE mulch lost 5.95 ± 0.03% and 3.62 ± 0.32% of its mass after incubated with P. knackmussii N1-2 and P. aeruginosa RD1-3 strains, respectively. Moreover, considerable pits and wrinkles were observed on PE.The hydrophobicity of PE films also decreased, and new oxygenic functional groups were detected on PE mulch by Fourier Transform Infrared Spectrometry (FTIR). Complete genome sequencing analysis indicated that two Pseudomonas strains encode genes for enzymes and metabolism pathways involved in PE degradation. The results provide a theoretical basis for further research that investigates the mechanism driving the degradation and metabolism of discarded PE in the environment.


Assuntos
Polietileno , Pseudomonas , Agricultura , Bactérias , Biodegradação Ambiental , Pseudomonas/genética
3.
Food Chem ; 371: 131385, 2022 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-34808778

RESUMO

The combination of multiple dietary polyphenols may have synergistic beneficial effects. And the beneficial effects can be further improved by the encapsulation of proteins. The interactions of procyanidin B2 (PB2) and/or dihydromyricetin (DMY) with ß-lactoglobulin (ß-LG) were investigated using multi-spectroscopic techniques and molecular docking. The structural change of ß-LG in the presence of PB2 and/or DMY was demonstrated by dynamic light scattering, Fourier transform infrared spectroscopy and circular dichroism spectroscopy. Response surface analysis was used to optimize the synergistic antioxidant activity between PB2 and DMY. Besides, the antioxidant activity, stability, in vitro digestion and cytotoxicity of PB2 and DMY in the binary and ternary systems were investigated. These studies will elucidate the interaction mechanism of PB2 and/or DMY with ß-LG. The research results can provide theoretical support for the development of functional foods and beverages with synergistic activity, improved stability and bioaccessibility, thereby promoting human health and preventing diseases.


Assuntos
Lactoglobulinas , Polifenóis , Antioxidantes , Digestão , Humanos , Simulação de Acoplamento Molecular , Espectroscopia de Infravermelho com Transformada de Fourier
4.
J Biomed Mater Res B Appl Biomater ; 110(1): 220-228, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34231969

RESUMO

Carbon dots (CDs) are nanomaterials with excellent photoluminescence property, usually used in the field of bioimaging tumor cells. However, its practical applicability in cancer therapeutics is limited by CDs' insensitive surface properties to complicated tumor microenvironment in vivo. Herein, a new type of innovative biomimetic nanoparticles has been formed with HeLa cell membranes (CM) and multifunctional CDs containing antitumor and bioimaging activities. The CDs are prepared by a facile one-step microwave-assisted procedure. Gallic acid is used as carbon resource and antitumor active molecule. Gelatin is treated as the nitrogen resource. Citric acid monohydrate is used as the auxiliary carbon source and the Hela CM is used for tumor targeting. A series of fluorescence analyses has proved its homotypic targeting and ability of diagnosis. Besides, in vitro and in vivo antitumor experiments further indicate their better antitumor efficiency. The findings show the totally new nanoparticles' feasibilities of dealing with the clinical therapy problems as well as applying for the integration of diagnosis and targeting therapy.

5.
Front Pharmacol ; 12: 750815, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34721038

RESUMO

The abnormal activation of the NLRP3 inflammasome is closely related to the occurrence and development of many inflammatory diseases. Targeting the NLRP3 inflammasome has been considered an efficient therapy to treat infections. We found that dihydrotanshinone I (DHT) specifically blocked the canonical and non-canonical activation of the NLRP3 inflammasome. Nevertheless, DHT had no relation with the activation of AIM2 or the NLRC4 inflammasome. Further study demonstrated that DHT had no influences on potassium efflux, calcium flux, or the production of mitochondrial ROS. We also discovered that DHT suppressed ASC oligomerization induced by NLRP3 agonists, suggesting that DHT inhibited the assembly of the NLRP3 inflammasome. Importantly, DHT possessed a significant therapeutic effect on NLRP3 inflammasome-mediated sepsis in mice. Therefore, our results aimed to clarify DHT as a specific small-molecule inhibitor for the NLRP3 inflammasome and suggested that DHT can be used as a potential drug against NLRP3-mediated diseases.

6.
Front Cardiovasc Med ; 8: 738044, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34722671

RESUMO

Background: Coronavirus disease 2019 (COVID-19) has outbroken in China and subsequently spread worldwide since the end of 2019. Chest computed tomography (CT) plays an important role in the diagnosis of lung diseases, but its value in the diagnosis of cardiac injury remains unknown. Methods: We enrolled 241 consecutive hospitalized patients (aged 61 ± 16 years, 115 males) with laboratory-confirmed COVID-19 at Renmin Hospital of Wuhan University from January 11 to March 2, 2020. They were divided into two groups according to whether major adverse cardiovascular events (MACEs) occurred during the follow-up. The anteroposterior diameter of the left atrium (LAD), the length of the left ventricle (LV), and cardiothoracic ratio (CTR) were measured. The values of myocardial CT were also recorded. Results: Of 241 patients, 115 patients (47.7%) had adverse cardiovascular events. Compared with no MACEs, patients with MACEs were more likely to have bilateral lesions (95.7% vs. 86.5%, p = 0.01). In multivariable analysis, bronchial wall thickening would increase the odds of MACEs by 13.42 (p = 0.01). LAD + LV and CTR was the best predictor for MACEs (area under the curve = 0.88, p < 0.001) with a sensitivity of 82.6% and a specificity of 80.2%. Plasma high-sensitivity troponin I levels in patients with cardiac injury showed a moderate negative correlation with minimum CT value (R 2 = -0.636, p < 0.001). Conclusions: Non-contrast chest CT can be a useful modality for detection cardiac injury and provide additional value to predict MACEs in COVID-19 patients.

7.
Front Neurosci ; 15: 769558, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34819836

RESUMO

Objectives: The aim of the study is to demonstrate the characteristic of motor development and MRI changes of related brain regions in preterm infants with different iron statuses and to determine whether the daily iron supplementation can promote motor development for preterm in early infancy. Methods: The 63 preterm infants were grouped into non-anemia with higher serum ferritin (NA-HF) group and anemia with lower serum ferritin (A-LF) group according to their lowest serum Hb level in the neonatal period as well as the sFer at 3 months old. Forty-nine participants underwent MRI scans and Infant Neurological International Battery (INFANIB) at their 3 months. At 6 months of corrected age, these infants received the assessment of Peabody Developmental Motor Scales (PDMS) after 2 mg/kg/day iron supplementation. Results: In total, 19 preterm infants were assigned to the NA-HF group while 44 preterm infants to the A-LF groups. The serum ferritin (sFer) level of the infants in A-LF group was lower than that in NA-HF group (44.0 ± 2.8 mg/L vs. 65.1 ± 2.8 mg/L, p < 0.05) and was with poorer scores of INFANIB (66.8 ± 0.9 vs. 64.4 ± 0.6, p < 0.05) at 3 months old. The structural connectivity between cerebellum and ipsilateral thalamus in the NA-HF group was significantly stronger than that in the A-LF group (n = 17, 109.76 ± 23.8 vs. n = 32, 70.4 ± 6.6, p < 0.05). The decreased brain structural connectivity was positively associated with the scores of PDMS (r = 0.347, p < 0.05). After 6 months of routine iron supplementation, no difference in Hb, MCV, MCHC, RDW, and sFer was detected between A-LF and NA-HF groups as well as the motor scores of PDMS-2 assessments. Conclusion: Iron status at early postnatal period of preterm infant is related to motor development and the enrichment of brain structural connectivity. The decrease in brain structural connectivity is related to the motor delay. After supplying 2 mg/kg of iron per day for 6 months, the differences in the iron status and motor ability between the A-LF and NA-HF groups were eliminated.

8.
Nanomaterials (Basel) ; 11(11)2021 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-34835566

RESUMO

In this study, magnetic Fe3O4 nanoparticles (NPs) were used as an effective enhancer to increase the biomass and total lipid production of Chlorella sp. UJ-3. It was found that the biomass of algal cells increased significantly when they were exposed to low concentrations of Fe3O4 NPs (20 mg/L), while the best total lipid content of algal cells was achieved when they were exposed to high concentrations of Fe3O4 NPs (100 mg/L). Therefore, we established a strategy to promote the growth and lipid accumulation of microalgae by initially exposing the algal cells to low concentrations of Fe3O4 NPs and then treating them with an increased concentration of Fe3O4 NPs after 12 days of culture. For this strategy, the biomass and total lipid production of algal cells increased by 50% and 108.7%, respectively, compared to the untreated control. The increase in lipid production and change in the fatty acid composition of Chlorella cells were found to help them to cope with the increased number of reactive oxygen species produced due to oxidative stress in alga cells after the addition of Fe3O4 NPs. This study provided a highly efficient way to improve the lipid production of microalgae using nanoparticles.

9.
Front Public Health ; 9: 772236, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34778197

RESUMO

Background: The mental health of racial/ethnic minorities in the U.S. has been disproportionately impacted by the COVID-19 pandemic. This study examined the extent to which disruptions in employment and housing, coronavirus-specific forms of victimization and racial bias independently and conjointly contributed to mental health risk among Asian, Black, and Latinx adults in the United States during the pandemic. Methods: This study reports on data from 401 Asian, Black, and Latinx adults (age 18-72) who participated in a larger national online survey conducted from October 2020-June 2021, Measures included financial and health information, housing disruptions and distress in response to employment changes, coronavirus related victimization distress and perceived increases in racial bias, depression and anxiety. Results: Asian participants had significantly higher levels of COVID-related victimization distress and perceived increases in racial bias than Black and Latinx. Young adults (<26 years old) were more vulnerable to depression, anxiety, and coronavirus victimization distress than older respondents. Having at least one COVID-related health risk, distress in response to changes in employment and housing disruptions, pandemic related victimization distress and perceived increases in racial bias were positively and significantly related to depression and anxiety. Structural equation modeling indicated COVID-related increases in racial bias mediated the effect of COVID-19 related victimization distress on depression and anxiety. Conclusions: COVID-19 has created new pathways to mental health disparities among racial/ethnic minorities in the U.S. by exacerbating existing structural and societal inequities linked to race. Findings highlight the necessity of mental health services sensitive to specific challenges in employment and housing and social bias experienced by people of color during the current and future health crises.


Assuntos
COVID-19 , Vítimas de Crime , Racismo , Adolescente , Adulto , Idoso , Emprego , Habitação , Humanos , Saúde Mental , Pessoa de Meia-Idade , Pandemias , SARS-CoV-2 , Estados Unidos/epidemiologia , Adulto Jovem
10.
China CDC Wkly ; 3(45): 948-953, 2021 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-34777900

RESUMO

What is already known about this topic?: Short-term PM2.5 exposure has been associated with hourly, 24-hour, daytime, and nighttime blood pressure (BP) levels, and further studies focusing whether and how the associations with other ambulatory BP monitoring indicators are warranted. What is added by this report?: This study observed that short-term PM2.5 exposure was associated with BP elevations and was the first to report the associations of short-term PM2.5 exposure with BP variability. Circadian rhythm of BP and BP load among hypertensive patients were found to be modified by controlled BP status or taking angiotensin receptor blockers (ARBs). What are the implications for public health practice?: This study suggested that antihypertensive therapy, especially with well-controlled BP status may be potential measurements to attenuate adverse impacts of PM2.5 for hypertensive patients with intermediate-to-high risk of cardiovascular disease (CVD).

11.
Artigo em Inglês | MEDLINE | ID: mdl-34784463

RESUMO

Direct emission of circularly polarized light from organic light-emitting diodes (OLEDs) is a research hotspot as it could increase the efficiency and significantly simplify device architecture of OLED-based 3D displays. In this study, R/S-OBS-Cz and R/S-OBS-TCz with axial chirality were efficiently prepared by using a stable chiral octahydro-binaphthol unit, carbazole/3,6-ditert-butylcarbazole donors, and a 5,5,10,10-tetraoxide acceptor. The chiral unit-acceptor-donor structure provides them not only thermally activated delayed fluorescence (TADF) characteristics with minor singlet-triplet energy gaps of 0.04 and 0.05 eV but also obvious circularly polarized photoluminescence (CPPL) phenomenon with dissymmetry factors of 8.7 × 10-4 and 6.4 × 10-4 in codoped films. Meanwhile, the CP-OLEDs prepared by enantiomers exhibit good device performances with the maximum external quantum efficiency reaching 20.3% and ideal efficiency roll-off as well as obvious CPEL properties with a |gEL| factor up to 1.0 × 10-3.

12.
Nanoscale ; 13(44): 18608-18615, 2021 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-34730599

RESUMO

Pyroptosis is an inflammation-dependent and self-cascade amplifying type of programmed cell death, serving as an effective means for activating the local immune response and improving the anticancer efficacy. As the effector of pyroptosis, gasdermin-E (GSDME) is silenced in most tumor cells. The gene silencing can be reversed by DNA demethylation, but the systemic side effects and toxicity of chemotherapeutic agents are inevitable. In this work, inhaled poly(lactic-co-glycolic acid) (PLGA) porous microspheres loaded with Decitabine (DAC) and Doxorubicin (DOX) (denoted as CO-MPs) were prepared to induce cell pyroptosis for orthotopic lung cancer therapy with fewer systemic side effects. The CO-MPs showed a hollow and porous spherical morphology and exhibited an excellent aerodynamic property, lung distribution and a sustained release effect. The CO-MPs could reverse GSDME silencing and elevate the expression of cleaved-caspase 3 in tumor cells. The cleaved-caspase 3 protein cleaved the GSDEM protein to obtain GSDME-N protein, causing the rupture of cell plasma membranes, release of cell contents and activation of the immune system. The CO-MPs could lead to the suppression of lung tumors, the decrease of the lung metastatic nodules in tumor-bearing mice and the induction of immunological memory that provides continuous protection from the tumor rechallenge. The inhalable microspheres loaded with DAC and DOX could be an effective strategy for lung cancer treatment via the pyroptosis mechanism.


Assuntos
Neoplasias Pulmonares , Piroptose , Animais , Desmetilação do DNA , Doxorrubicina/farmacologia , Neoplasias Pulmonares/tratamento farmacológico , Camundongos , Receptores de Estrogênio
13.
Acta Biomater ; 2021 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-34774783

RESUMO

The existing adverse effects of copper in copper-containing intrauterine devices (Cu-IUDs) have raised concerns regarding their use. These adverse effects include burst release of cupric ions (Cu2+) at the initial stage and an increasingly rough surface of the Cu-IUDs. In this study, we investigated the use of two copper alloys, Cu-38Zn and H62 as the new upgrading or alternative material for IUDs. Their corrosive properties were studied in simulated uterine fluid (SUF) by using electrochemical methods, with pure Cu as a control. We studied the in vitro long-term corrosion behaviors in SUF, cytotoxicity to uterine cells (human endometrial epithelial cells and human endometrial stromal cells), in vivo biocompatibility and contraceptive efficacy of pure Cu, H62, and Cu-38Zn. In the first month, the burst release rate of Cu2+ in the Cu-38Zn group was significantly lower than those in the pure Cu and H62 groups. The in vitro cytocompatibility Cu-38Zn was better than that of pure Cu and H62. Moreover, Cu-38Zn showed improved tissue biocompatibility in vivo experiments. Therefore, the contraceptive efficacy of the Cu-38Zn is still maintained as high as the pure Cu while the adverse effects are significantly eased, suggesting that Cu-38Zn can be a suitable potential candidate material for IUDs. STATEMENT OF SIGNIFICANCE: The existing adverse effects associated with the intrinsic properties of copper materials for copper-containing intrauterine devices (Cu-IUD) are of concern in their employment. Such as, burst release of cupric ions (Cu2+) at the initial stage and an increasingly rough surface of the Cu-IUD. In this work, Cu alloyed with a high amount of bioactive Zn was used for a Cu-IUD. The Cu-38Zn alloy exhibited reduced burst release of Cu2+ within the first month compared with the pure Cu and H62. Furthermore, the Cu-38Zn alloy displayed significantly improved biocompatibility and a much smoother surface. Therefore, high antifertility efficacy of the Cu-38Zn alloy was well maintained, while the adverse effects are significantly eased, suggesting that the Cu-38Zn alloy is promising for a Cu-IUD.

14.
Front Microbiol ; 12: 719599, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34803940

RESUMO

Increasing evidences suggest that the gut microbiota have their contributions to the hypertension, but the metagenomic characteristics and potential regulating mechanisms in primary hypertension patients taking antihypertension drugs are not clear yet. We carried out a metagenomic analysis in 30 primary hypertension patients taking antihypertension medications and eight healthy adults without any medication. We found that bacterial strains from species, such as Bacteroides fragilis, Bacteroides vulgatus, Escherichia coli, Klebsiella pneumoniae, and Streptococcus vestibularis, were highly increased in patients; and these strains were reported to generate glycan, short-chain fatty acid (SCFA) and trimethylamine (TMA) or be opportunistic pathogens. Meanwhile, Dorea longicatena, Eubacterium hallii, Clostridium leptum, Faecalibacterium prausnitzii, and some other strains were greatly decreased in the patient group. The Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis found that ortholog groups and pathways related to glycan biosynthesis and multidrug resistance were significantly increased in the patient group, and some of the hub genes related to N-glycan biosynthesis were increased in the patient group, while those related to TMA precursor metabolism and amino acid metabolism both increased and decreased in the patient group. Metabolites tested by untargeted liquid chromatography-mass spectrometry (LC-MS) proved the decrease of acetic acid, choline, betaine, and several amino acids in patients' fecal samples. Moreover, meta-analysis of recent studies found that almost all patients were taking at least one kind of drugs that were reported to regulate adenosine monophosphate-activated protein kinase (AMPK) pathway, so we further investigated if AMPK regulated the metagenomic changes by using angiotensin II-induced mouse hypertensive model on wild-type and macrophage-specific AMPK-knockout mice. We found that the changes in E. coli and Dorea and glycan biosynthesis-related orthologs and pathways were similar in our cohort and hypertensive wild-type mice but reversed after AMPK knockout. These results suggest that the gut microbiota-derived glycan, SCFA, TMA, and some other metabolites change in medication-taking primary hypertension patients and that medications might promote gut microbiota glycan biosynthesis through activating macrophage-AMPK.

15.
ACS Omega ; 6(45): 30826-30833, 2021 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-34805711

RESUMO

Plant bacteria such as Xanthomonas axonopodis pv. citri (Xac), Pseudomonas syringae pv. actinidiae (Psa), Xanthomonas oryzae pv. oryzae (Xoo), and tobacco mosaic virus (TMV) have created huge obstacles to the global trade of food and economic crops. However, traditional chemical agents used to control these plant diseases have gradually become disadvantageous due to long-term irregular use. Therefore, finding new and efficient antibacterial and antiviral agents is becoming imperative. In this study, a series of myricetin derivatives containing a quinazolinone moiety were designed and synthesized, and the antibacterial and antiviral activities of these compounds were evaluated. The bioassay results showed that some target compounds exhibited good antibacterial activities in vitro and antiviral activities in vivo. Among them, the median effective concentration (EC50) value of compound L18 against Xac was 16.9 µg/mL, which was better than those of the control drugs bismerthiazol (BT) (62.2 µg/mL) and thiodiazole copper (TC) (97.5 µg/mL). Scanning electron microscopy (SEM) results confirmed that compound L18 inhibited the growth of Xac by affecting the morphology of cells. Microscale thermophoresis (MST) test results indicated that the dissociation constant (K d) value of compound L11 against TMV-CP was 0.012 µM, which was better than that of the control agent ningnanmycin (2.726 µM). This study reveals that myricetin derivatives containing a quinazolinone moiety are potential antibacterial and antiviral agents.

16.
J Orthop Surg Res ; 16(1): 673, 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34781979

RESUMO

INTRODUCTION: Steroid-induced osteonecrosis of the femoral head (ONFH) is a disease of the bone. Metabolism and genetic factors are generally considered to play an important role. The purpose of this study was to investigate the relationship between single-nucleotide polymorphisms (SNPs) in MIR17HG and MIR155HG and the risk of steroid-induced ONFH in the population of northern China. METHODS: A total of 199 steroid-induced ONFH patients and 506 healthy controls were recruited for the study. Four SNPs of MIR17HG and seven SNPs of MIR155HG were genotyped by Sequenom MassARRAY. ORs and 95% CIs were used to evaluate the relationship between these SNPs and steroid-induced ONFH. RESULTS: In the codominant model, patients with the MIR17HG SNPs (rs7318578) AA genotype had an increased risk of steroid-induced ONFH (OR = 1.79, p = 0.039); in the recessive model, patients with the MIR17HG SNP (rs7318578) AA genotype had an increased risk of steroid-induced ONFH (OR = 1.78, p = 0.032). Stratified analysis showed that a MIR17HG SNP (rs7318578) and the MIR155HG SNPs (rs77218221, rs11911469, rs34904192 and rs4143370) were closely related to different unornamented phenotypes of steroid-induced ONFH. Analysis of the clinical indicators revealed significant differences in high-density lipoprotein (HDL-C) levels between the ONFH group and the control group (p = 0.005). In the MIR17HG SNP (rs75267932), patients with different genotypes had different levels of triglyceride (TG). The MIR155HG SNPs (rs77699734, rs1893650, and rs34904192) showed differences in triglyceride (TG), high-density lipoprotein (HDL-C) and low-density lipoprotein (LDL-C) levels in patients with different genotypes. CONCLUSION: Our results confirm that MIR17HG and MIR155HG gene mutations are associated with steroid-induced ONFH susceptibility in the population of northern China, providing new evidence for the early detection and prevention of ONFH.

17.
CNS Neurosci Ther ; 2021 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-34767694

RESUMO

AIMS: This study aimed to explore the pathomechanism of a mutation on the leucine-rich glioma inactivated 1 gene (LGI1) identified in a family having autosomal dominant lateral temporal lobe epilepsy (ADLTE), using a precise knock-in mouse model. METHODS AND RESULTS: A novel LGI1 mutation, c.152A>G; p. Asp51Gly, was identified by whole exome sequencing in a Chinese family with ADLTE. The pathomechanism of the mutation was explored by generating Lgi1D51G knock-in mice that precisely phenocopied the epileptic symptoms of human patients. The Lgi1D51G / D51G mice showed spontaneous recurrent generalized seizures and premature death. The Lgi1D51G /+ mice had partial epilepsy, with half of them displaying epileptiform discharges on electroencephalography. They also showed enhanced sensitivity to the convulsant agent pentylenetetrazole. Mechanistically, the secretion of Lgi1 was impaired in the brain of the D51G knock-in mice and the protein level was drastically reduced. Moreover, the antiepileptic drugs, carbamazepine, oxcarbazepine, and sodium valproate, could prolong the survival time of Lgi1D51G / D51G mice, and oxcarbazepine appeared to be the most effective. CONCLUSIONS: We identified a novel epilepsy-causing mutation of LGI1 in humans. The Lgi1D51G /+ mouse model, precisely phenocopying epileptic symptoms of human patients, could be a useful tool in future studies on the pathogenesis and potential therapies for epilepsy.

18.
Public Health Genomics ; : 1-9, 2021 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-34788764

RESUMO

BACKGROUND: Steroid-induced osteonecrosis of the femoral head (ONFH) is aseptic necrosis of the femoral head caused by glucocorticoid use. Once necrotic femoral head necrosis occurs, it irreversibly affects the quality of life seriously. Studies have shown that the susceptibility to steroid-induced ONFH is likely to be related to the variation of miRNA-coding genes. Therefore, this study aimed was to investigate the effect of MIR3142HG on steroid-induced ONFH. METHODS: Agena MassARRAY was used to genotype MIR3142HG gene rs1582417, rs2431689, rs7727155, and rs17057846 in 199 patients and 725 healthy people. A genetic model and haplotype analysis were used to evaluate the relationship between the MIR3142HG polymorphism and the risk of steroid-induced ONFH. The odds ratio and 95% confidence intervals were obtained through logistic regression to assess the influence of gene polymorphisms on the occurrence of steroid-induced ONFH. RESULTS: The consequences show that rs7727115 is a protective factor, it could reduce the risk of steroid-induced ONFH, and rs1582417 could increase the risk of steroid-induced ONFH. In the genetic model, rs1582417 was associated with increased risk of alcohol-induced ONFH in dominant model and log-additive model. rs7727115 showed a decreased risk in codominant model, dominant model, and log-additive model. In addition, rs2431689 is related to HDL-C (p = 0.012) and ApoA1 (p = 0.010) levels, and rs17057846 (p = 0.024) is related to ApoB levels. Thelinkage analysis indicated 3 single-nucleotide polymorphisms (rs2431689, rs7727115, and rs17057846) in MIR3142HG with significant chain imbalance. In addition, haplotype "GGG" of MIR3142HG was found out and is harmful for steroid-induced ONFH. CONCLUSION: Our results first confirm that the genetic polymorphism of MIR3142HG is associated with steroid-induced ONFH susceptibility in Chinese Han population.

19.
Oncotarget ; 12(20): 2068-2074, 2021 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-34611480

RESUMO

Peripheral T-cell lymphoma (PTCL) is characterized by poor outcomes. We and others have shown that targeting the NEDD8-activating enzyme (NAE) with an investigational inhibitor pevonedistat deregulates cell cycle and mitosis in lymphoma and leukemia. Here, we report that PTCL is characterized by increased rate of chromosomal instability. NAE inhibition promotes cell cycle arrest and induces multipolar anaphases in T-cell lymphoma cell lines, resulting in apoptosis, also observed in primary malignant PTCL cells treated with pevonedistat. We identified p27Kip1 as a mediator of anaphase catastrophe in these cells. Targeting neddylation with pevonedistat may be a promising approach to treatment of PTCL.

20.
Front Pharmacol ; 12: 745561, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34675811

RESUMO

Liver fibrosis is an abnormal proliferation of connective tissue in the liver caused by various pathogenic factors. Chronic liver injury leads to release of inflammatory cytokines and reactive oxygen species (ROS) from damaged hepatocytes, which activates hepatic stellate cells (HSCs) to secrete extracellular matrix proteins, thereby leading to fibrosis. Thus, inhibition of hepatocyte injury and HSC activation, and promotion of apoptosis of activated HSCs are important strategies for prevention of liver fibrosis. In this study, we showed that the germacrone (GER), the main component in the volatile oil of zedoary turmeric, inhibited hepatic fibrosis by regulating multiple signaling pathways. First, GER improved the cell survival rate by inhibiting the production of ROS after hepatocyte injury caused by acetaminophen (APAP). In addition, GER inhibited the activation of HSCs and expression of collagen I by blocking TGF-ß/Smad pathway in LX-2 cells. However, when the concentration of GER was higher than 60 µM, it specifically induced HSCs apoptosis by promoting the expression and activation of apoptosis-related proteins, but it had no effect on hepatocytes. Importantly, GER significantly attenuated the methionine- and choline-deficient (MCD) diet-induced liver fibrosis by inhibiting liver injury and the activation of HSCs in vivo. In summary, GER can not only protect hepatocytes by reducing ROS release to avoid the liver injury-induced HSC activation, but also directly inhibit the activation and survival of HSCs by regulating TGF-ß/Smad and apoptosis pathways. These results demonstrate that GER can be used as a potential therapeutic drug for the treatment of liver fibrosis.

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