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1.
Methods Mol Biol ; 2326: 197-201, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34097269

RESUMO

To assess the toxicities of gas/aerosol, inhalation exposure model is necessary. Especially important is the inhalation exposure early in life. Traditional inhalation exposure method requires specific instruments and may have to imitate the exposure either days before or after birth. Here, a new inhalation exposure method is introduced, which may be performed without any specific instruments and effectively expose late stage chicken embryos to gas/aerosol very early-in-life by inhalation. This method may facilitate the risk assessment and mechanistic studies regarding the early-in-life effects of gas/aerosol exposure.

2.
Orthop Surg ; 2021 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-33955670

RESUMO

OBJECTIVE: This study was performed to evaluate the function and satisfaction outcome of patients with rheumatoid arthritis (RA) who underwent total knee arthroplasty (TKA) with high-flexion prostheses. MATERIALS AND METHODS: Twenty-two patients (35 knees) using high-flexion prostheses (Zimmer, Warsaw, IN) were followed up for a period of 7-11 years from February 2007 to December 2009. Clinical and radiographic follow-up was performed using Hospital for Special Surgery (HSS), Short-Form 36 scores (SF-36), American Knee Society score (KSS), and Knee Society Total Knee Arthroplasty Roentgenographic Evaluation and Scoring System. Patient satisfaction assessments took place at the final follow-up sessions using the Marsh Satisfaction Questionnaire. RESULTS: The average ROM improved from preoperative 68.43° ± 33.78° to 95.54° ± 7.03° at the final follow-up. The HSS score and KSS score for pain improved from (46.49 ± 12.73) points to (85.46 ± 3.90) points and from 20.57 ± 5.91 points to 47.43 ± 3.51 points at the follow-up evaluation, respectively. Physical Component Summary(PCS) and Physical Component Summary (MCS) scores were 45.38 and 52.56, respectively by the end of follow-up. Deep venous thrombosis developed in one patient and one patient required surgical revision due to infection. There were no instances of prosthetic loosening. The satisfaction rate of patients was 95.5%. CONCLUSION: Although this particular model of TKA did not yield high-flexion angles (ie, 140°) required for kneeling, squatting, or rising from the floor, significant clinical and radiographic gains were evident in these patients with RA.

3.
Mol Med Rep ; 24(1)2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33955513

RESUMO

Autophagy serves a crucial role in the etiology of kidney diseases, including drug­induced renal impairment, inherited kidney disease, diabetic nephropathy and aristolochic acid nephropathy (AAN) and is, therefore, a potential target for treatment. We previously demonstrated that rapamycin could attenuate AAN in mice; however, the underlying mechanism remains to be elucidated. Therefore, whether the renal protective effect of rapamycin (an autophagy activator) is related to autophagy in aristolochic acid (AA)­treated mice was of particular interest. The pathophysiological roles of rapamycin were investigated in AA­induced nephrotoxicity in mice and the mechanisms of rapamycin action were explored by evaluating the modulation of autophagy in rapamycin­treated mice and cultured renal tubular epithelial cells. Supplementation with rapamycin reversed AA­induced kidney injury in mice and improved AA­induced autophagy damage in vivo and in vitro. Mechanistically, rapamycin inhibited the renal expression of phosphorylated (p­)mammalian target of rapamycin (mTOR) and p­ribosomal S6 protein kinase 1, which in turn activated renal autophagy and decreased apoptosis, probably by removing AA­elicited damaged mitochondria and misfolded proteins. The findings of the present study demonstrated that rapamycin protects against AA­induced nephropathy by activating the mTOR­autophagy axis and suggested that rapamycin may be a promising pharmacological target for the treatment of AAN.

4.
Int J Mol Med ; 47(6)2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33907823

RESUMO

Radiation is one of the main methods for the treatment of colorectal cancer (CRC) before or after surgery. However, radiotherapy tolerance of patients with CRC is often a major concern. Interferon regulatory factor 1 (IRF1) is a member of the IRF family and is involved in the development of multiple diseases, including tumors. The present study investigated the role of IRF1 in the development and radiation sensitivity of CRC. Immunohistochemistry was performed to examine the expression levels of IRF1 in tissue samples from patients with CRC, as well as in nude mice. MTT, 5­ethynyl­20­deoxyuridine, colony formation, cell cycle alteration and apoptosis assays were performed in CRC cell lines. Western blotting and immunofluorescence were used to detect the expression levels of a series of proteins. RNA sequencing was applied to identify genes whose expression was upregulated by IRF1 overexpression. Xenograft nude mouse models and hematoxylin and eosin staining were used to validate the present findings in vivo. It was revealed that the expression levels of IRF1 were significantly lower in CRC tissues than in adjacent tissues. IRF1 upregulation inhibited cell proliferation and colony formation, caused G1 cell arrest, promoted cell apoptosis, and enhanced the sensitivity of CRC cells to X­ray irradiation. The role of IRF1 in promoting the radiosensitivity of CRC was further demonstrated in nude mice with CRC xenografts. In addition, RNA sequencing revealed that overexpression of IRF1 in CRC cells significantly increased the expression levels of interferon­induced protein family members interferon α inducible protein 6, interferon induced transmembrane protein 1 and interferon induced protein 35 (fold change >2.0). In summary, the present study demonstrated that the upregulation of IRF1 inhibited the progression and promoted the radiosensitivity of CRC, likely by regulating interferon­induced proteins.

5.
Nanoscale ; 13(17): 8107-8117, 2021 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-33881108

RESUMO

Parkinson's disease (PD) is the second most prevalent neurodegenerative disease. Nitrated α-synuclein (α-syn) in the blood is a potentially efficient biomarker for PD in its early stages. In this work, an ultrasensitive electrochemical immunosensor was developed for the specific detection of nitrated α-syn. Supramolecule-mediated AuNP composites (GNCs) were modified on the gold electrode as a sensing film to capture anti-nitrated α-syn. Basic characterization studies revealed that GNCs were composed of abundant binding sites and had high conductivity with a large surface area, biocompatibility, and remarkable electrochemical activity. Anti-α-syn-modified magnetic nanoparticles (MNPs) were used as signal amplification tags to construct a sensitive sandwich assay. With a high specific surface area, strong conductivity, and abundant active sites, GNCs as an amplifying matrix can enhance the performance of the immunoassay and obtain preliminary signal amplification. MNPs showed excellent stability and led to a net decrease in the charge-transfer resistance due to their unique spherical structure and high conductivity, resulting in a sensitive electrochemical signal change according to the nitrated α-syn concentration in the sample. Therefore, this simple nitrated α-syn immunoassay with sensitivity and selectivity has potential for practical clinical applications.


Assuntos
Técnicas Biossensoriais , Nanopartículas Metálicas , Doenças Neurodegenerativas , Técnicas Eletroquímicas , Ouro , Humanos , Imunoensaio , Limite de Detecção , Fenômenos Magnéticos , Nitratos , alfa-Sinucleína
6.
Plants (Basel) ; 10(3)2021 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-33799776

RESUMO

Functional characterization of plant agrichemical transporters provided an opportunity to discover molecules that have a high mobility in plants and have the potential to increase the amount of pesticides reaching damage sites. Agrobacterium-mediated transient expression in tobacco is simple and fast, and its protein expression efficiency is high; this system is generally used to mediate heterologous gene expression. In this article, transient expression of tobacco nicotine uptake permease (NtNUP1) and rice polyamine uptake transporter 1 (OsPUT1) in Nicotiana benthamiana was performed to investigate whether this system is useful as a platform for studying the interactions between plant transporters and pesticides. The results showed that NtNUP1 increases nicotine uptake in N. benthamiana foliar discs and protoplasts, indicating that this transient gene expression system is feasible for studying gene function. Moreover, yeast expression of OsPUT1 apparently increases methomyl uptake. Overall, this method of constructing a transient gene expression system is useful for improving the efficiency of analyzing the functions of plant heterologous transporter-encoding genes and revealed that this system can be further used to study the functions of transporters and pesticides, especially their interactions.

7.
J Vis Exp ; (169)2021 03 21.
Artigo em Inglês | MEDLINE | ID: mdl-33818575

RESUMO

Chicken embryos are a classical model in developmental studies. During the development of chicken embryos, the time window of heart development is well-defined, and it is relatively easy to achieve precise and timely exposure via multiple methods. Moreover, the process of heart development in chicken embryos is similar to mammals, also resulting in a four-chambered heart, making it a valuable alternative model in the assessment of developmental cardiotoxicities. In our lab, the chicken embryo model is routinely used in the assessment of developmental cardiotoxicities following exposure to various environmental pollutants, including per- and polyfluoroalkyl substances (PFAS), particulate matter (PMs), diesel exhaust (DE) and nano materials. The exposure time can be freely selected based on the need, from the beginning of development (embryonic day 0, ED0) all the way to the day prior to hatch. The major exposure methods include air-cell injection, direct microinjection, and air-cell inhalation (originally developed in our lab), and the currently available endpoints include cardiac function (electrocardiography), morphology (histological assessments) and molecular biological assessments (immunohistochemistry, qRT-PCR, western blotting, etc.). Of course, the chicken embryo model has its own limitations, such as limited availability of antibodies. Nevertheless, with more laboratories starting to utilize this model, it can be used to make significant contributions to the study of developmental cardiotoxicities.


Assuntos
Cardiotoxicidade/fisiopatologia , Animais , Embrião de Galinha , Galinhas
8.
Adv Mater ; 33(18): e2007833, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33786873

RESUMO

The global demand for clean and safe water will continue to grow well into the 21st century. Moving forward, the lack of access to clean water, which threatens human health and strains precious energy resources, will worsen as the climate changes. Therefore, future innovations that produce potable water from contaminated sources must be sustainable. Inspired by nature, a solar absorber gel (SAG) is developed to purify water from contaminated sources using only natural sunlight. The SAG is composed of an elastic thermoresponsive poly(N-isopropylacrylamide) (PNIPAm) hydrogel, a photothermal polydopamine (PDA) layer, and a sodium alginate (SA) network. Production of the SAG is facile; all processing is aqueous-based and occurs at room temperature. Remarkably, the SAG can purify water from various harmful reservoirs containing small molecules, oils, metals, and pathogens, using only sunlight. The SAG relies on solar energy to drive a hydrophilic/hydrophobic phase transformation at the lower critical solution temperature. Since the purification mechanism does not require water evaporation, an energy-intensive process, the passive solar water-purification rate is the highest reported. This discovery can be transformative in the sustainable production of clean water to improve the quality of human life.

9.
Brain Inj ; 35(5): 554-562, 2021 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-33749412

RESUMO

Background: This study aims to describe TBI-related hospitalizations for the whole population and identify factors associated with in-hospital mortality among elderly (≥65 years) patients hospitalized with TBI in Texas.Methods: Using Texas Hospital Discharge Data from 2012 to 2014, TBI-related hospitalizations were identified using International Classification of Diseases - Ninth Revision - Clinical Modification (ICD-9-CM) codes. Rates for age and gender were estimated using U.S. Census data. Univariate and multivariate analyses were used to identify factors associated with in-hospital mortality among those aged at least 65 years.Results: There were 51,419 TBI-related hospitalizations from 2012 to 2014 in Texas. Falls were the leading cause of TBI-related hospitalizations 6235 (36.64%), 6595 (38.40%), and 5412 (37.59%) for 2012, 2013, and 2014, respectively. Males had higher rates of hospitalizations while rates were highest for those above 80 years of age. Compared to Whites, Hispanics had 1.18 higher adjusted odds of in-hospital mortality [OR = 1.18: 95% CI (1.01-1.40)]. Similarly, adjusted odds of in-hospital mortality were higher among males [OR = 1.55: 95% CI (1.36-1.77)].Conclusion: This study provided evidence of demographic disparities in the burden and outcome of TBI in Texas, findings could serve as a foundation for targeted TBI prevention interventions.

10.
Medicine (Baltimore) ; 100(12): e24813, 2021 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-33761641

RESUMO

BACKGROUND: The study aims to evaluate the effectiveness and safety of Baduanjin exercise for patients with cervical spondylosis (CS). METHODS: We will retrieve a randomized controlled trial of Baduanjin for CS from the following electronic databases establishment to May 2021: The Cochrane Library, MEDLINE, EMBASE, Web of Science, Springer, World Health Organization International Clinical Trials Registry Platform (ICTRP), China National Knowledge Infrastructure (CNKI), Wan-fang database, Chinese Scientific Journal Database (VIP), Chinese Biomedical Literature Databases (CBM), and other databases. Two independent researchers will operate article retrieval, duplication removing, screening, quality evaluation, and data analyses by Review Manager (V.5.3.5). Meta-analyses, subgroup analysis, and/or descriptive analysis will be performed based on the included data conditions. RESULTS: The results of this study will provide researchers in the field of CS with a current synthesis of high-quality evidence. CONCLUSION: This conclusion of this study will provide the evidence of whether Baduanjin is an effective and safe intervention for patients with CS. PROSPERO REGISTRATION NUMBER: CRD42020211019.


Assuntos
Qigong/métodos , Espondilose/terapia , Humanos , Metanálise como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto , Revisões Sistemáticas como Assunto , Resultado do Tratamento
11.
Cell Death Dis ; 12(2): 169, 2021 02 10.
Artigo em Inglês | MEDLINE | ID: mdl-33568627

RESUMO

Cisplatin is one of the most effective chemotherapy drugs and is widely used in the treatment of cancer, including hepatocellular carcinoma (HCC) and cervical cancer, but its therapeutic benefit is limited by the development of resistance. Our previous studies demonstrated that BCAT1 promoted cell proliferation and decreased cisplatin sensitivity in HCC cells. However, the exact role and mechanism of how BCAT1 is involved in cisplatin cytotoxicity remain undefined. In this study, we revealed that cisplatin triggered autophagy in cancer cells, with an increase in BCAT1 expression. The cisplatin-induced up-regulation of BCAT1 decreased the cisplatin sensitivity by regulating autophagy through the mTOR signaling pathway. In addition, branched-chain amino acids or leucine treatment inhibited cisplatin- or BCAT1-mediated autophagy and increased cisplatin sensitivity by activating mTOR signaling in cancer cells. Moreover, inhibition of autophagy by chloroquine increased cisplatin sensitivity in vivo. Also, the knockdown of BCAT1 or the administration of leucine activated mTOR signaling, inhibited autophagy, and increased cisplatin sensitivity in cancer cells in vivo. These findings demonstrate a new mechanism, revealing that BCAT1 decreases cisplatin sensitivity in cancer cells by inducing mTOR-mediated autophagy via branched-chain amino acid leucine metabolism, providing an attractive pharmacological target to improve the effectiveness of chemotherapy.

12.
Anal Chem ; 93(7): 3403-3410, 2021 02 23.
Artigo em Inglês | MEDLINE | ID: mdl-33556238

RESUMO

Rapid, quantitative, and group-targeting detection of total benzodiazepines (BZDs) is critical to create an accurate judgement in emergent medical and forensic settings. Large-size (111) faceted Ag nanosheets decorated with small ZnO nanoparticles were designed as the prominent surface-enhanced Raman scattering substrate, which possessed advantages of specific metal facets and additional charge-transfer (CT) effect from the semiconductor. The vital and bridge role of ZnO in the CT effect was systematically studied via experimental investigations and molecular dynamics simulation, which proves the essentiality of an appropriate ZnO decoration density. Upon determining optimal Ag NS/ZnO hybrids, a calibration curve of estazolam was established with a 0.5 nM detection limit. Based on the obtained curve, group-targeting screening was achieved toward total concentrations of five BZDs (estazolam, oxazepam, alprazolam, triazolam, and lorazepam). Importantly, the total concentrations of BZDs in mice serum were accurately monitored with changing analytical time during the metabolic process, which was in agreement with the tendency measured by liquid chromatography with tandem mass spectrometry.

13.
Environ Int ; 148: 106378, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33508708

RESUMO

Low birth weight is an important risk factor for many co-morbidities both in early life as well as in adulthood. Numerous studies report associations between prenatal exposure to particulate matter (PM) air pollution and low birth weight. Previous systematic reviews and meta-analyses report varying effect sizes and significant heterogeneity between studies, but did not systematically evaluate the quality of individual studies or the overall body of evidence. We conducted a new systematic review to determine how prenatal exposure to PM2.5, PM10, and coarse PM (PM2.5-10) by trimester and across pregnancy affects infant birth weight. Using the Navigation Guide methodology, we developed and applied a systematic review protocol [CRD42017058805] that included a comprehensive search of the epidemiological literature, risk of bias (ROB) determination, meta-analysis, and evidence evaluation, all using pre-established criteria. In total, 53 studies met our inclusion criteria, which included evaluation of birth weight as a continuous variable. For PM2.5 and PM10, we restricted meta-analyses to studies determined overall as "low" or "probably low" ROB; none of the studies evaluating coarse PM were rated as "low" or "probably low" risk of bias, so all studies were used. For PM2.5, we observed that for every 10 µg/m3 increase in exposure to PM2.5 in the 2nd or 3rd trimester, respectively, there was an associated 5.69 g decrease (I2: 68%, 95% CI: -10.58, -0.79) or 10.67 g decrease in birth weight (I2: 84%, 95% CI: -20.91, -0.43). Over the entire pregnancy, for every 10 µg/m3 increase in PM2.5 exposure, there was an associated 27.55 g decrease in birth weight (I2: 94%, 95% CI: -48.45, -6.65). However, the quality of evidence for PM2.5 was rated as "low" due to imprecision and/or unexplained heterogeneity among different studies. For PM10, we observed that for every 10 µg/m3 increase in exposure in the 3rd trimester or the entire pregnancy, there was a 6.57 g decrease (I2: 0%, 95% CI: -10.66, -2.48) or 8.65 g decrease in birth weight (I2: 84%, 95% CI: -16.83, -0.48), respectively. The quality of evidence for PM10 was rated as "moderate," as heterogeneity was either absent or could be explained. The quality of evidence for coarse PM was rated as very low/low (for risk of bias and imprecision). Overall, while evidence for PM2.5 and course PM was inadequate primarily due to heterogeneity and risk of bias, respectively, our results support the existence of an inverse association between prenatal PM10 exposure and low birth weight.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Efeitos Tardios da Exposição Pré-Natal , Adulto , Poluentes Atmosféricos/análise , Poluentes Atmosféricos/toxicidade , Poluição do Ar/efeitos adversos , Poluição do Ar/análise , Peso ao Nascer , Exposição Ambiental/análise , Feminino , Humanos , Lactente , Recém-Nascido , Exposição Materna/efeitos adversos , Material Particulado/análise , Gravidez , Efeitos Tardios da Exposição Pré-Natal/epidemiologia
14.
Toxicol Lett ; 339: 88-96, 2021 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-33423876

RESUMO

The roots of Averrhoa carambola L. (Oxalidaceae) have a long history of medical use in traditional Chinese medicine for treating diabetes and diabetic nephropathy. 2-dodecyl-6-methoxycyclohexa-2, 5-diene-1, 4-dione (DMDD) was isolated from the tuberous roots of Averrhoa carambola L. The purpose of this study was to investigate the beneficial effect of DMDD on the advanced glycation end-product-mediated renal injury in type 2 diabetic KKAy mice with regard to prove its efficacy by local traditional practitioners in the treatment of kidney frailties in diabetics. KKAy mice were orally administrated DMDD (12.5, 25, 50 mg/kg body weight/d) or aminoguanidine (200 mg/kg body weight/d) for 8 weeks. Hyperglycemia, renal AGE formation, and the expression of related proteins, such as the AGE receptor, nuclear factor-κB, transforming growth factor-ß1, and Nε-(carboxymethyl)lysine, were markedly decreased by DMDD. Diabetes-dependent alterations in proteinuria, serum creatinine, creatinine clearance, and serum urea-N and glomerular mesangial matrix expansion were attenuated after treatment with DMDD for 8 weeks. The activities of superoxide dismutase and glutathione peroxidase, which are reduced in the kidneys of KKAy mice, were enhanced by DMDD. These findings suggest that DMDD may inhibit the progression of diabetic nephropathy and may be a therapeutic agent for regulating several pharmacological targets to treat or prevent of diabetic nephropathy.

16.
Ecotoxicol Environ Saf ; 208: 111614, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33396134

RESUMO

A novel gill cell line from pearl gentian grouper (Epinephelus lanceolatus♂×Epinephelus fuscoguttatus♀, PGGG cell line) was established, its application in cadmium (Cd) toxicology was demonstrated in this study. Primary cultures and PGGG subcultures were carried out at 25 °C in Dulbecco's Modified Eagle medium/F12 medium (1:1; pH 7.2) supplemented with 15% fetal bovine serum (FBS). Primary PGGG cells were spindle-shaped, proliferated into a confluent monolayer within two weeks and were continuously subcultured over passage 60. The growth of cells at passages 20, 40, and 60 was examined. Chromosome analysis revealed that the chromosomal number of normal PGGG cells was 48, but the number of cells with the normal chromosomes number decreased during the passaging process. Cadmium is one of the most toxic metals in aquatic systems and has been associated with multiple animal and human health problems. To interpret the cytotoxicity and related mechanisms of cadmium, PGGG cells were used as an in vitro model. After treatment with cadmium at concentrations ranging from 1 µM to 500 µM, PGGG cells demonstrated dose- and time-dependent cytotoxicity, manifested as morphological abnormalities and a viability decline. Further, it was found that the reactive oxygen species (ROS) and malondialdehyde (MDA) levels were elevated following cadmium exposure, and related genes involved in the antioxidant system, including those encoding catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR), and Kelch-like- ECH-associated protein 1 (Keap1), were regulated differently. In addition, PGGG cells treated with cadmium had the typical features associated with apoptosis, including phosphatidylserine (PS) externalization; upregulated expression of caspase-3, -8, and -9; and apoptotic body formation. In general, the PGGG cell line may serve as a useful tool for studying the toxic mechanisms of cadmium or other toxicants or for toxicity testing and environment monitoring.


Assuntos
Apoptose/efeitos dos fármacos , Bass , Cádmio/toxicidade , Expressão Gênica/efeitos dos fármacos , Brânquias , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Poluentes Químicos da Água/toxicidade , Animais , Antioxidantes/metabolismo , Catalase/genética , Catalase/metabolismo , Técnicas de Cultura de Células , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Brânquias/citologia , Proteína 1 Associada a ECH Semelhante a Kelch/genética , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/genética , Espécies Reativas de Oxigênio/metabolismo , Superóxido Dismutase/genética , Superóxido Dismutase/metabolismo
17.
Nan Fang Yi Ke Da Xue Xue Bao ; 41(1): 55-63, 2021 Jan 30.
Artigo em Chinês | MEDLINE | ID: mdl-33509753

RESUMO

OBJECTIVE: To investigate the role of NDUFA13 inactivation in the pathogenesis of spontaneous hepatitis in mice and explore the possible mechanisms. METHODS: Hepatocyte-specific NDUFA13 knockout (NDUFA13fl/-) mice were generated by intercrossing NDUFA13fl/fl and Alb-Cre mice based on Cre/loxP transgenic technology, and tail and liver DNA of the mice was genotyped by PCR analysis. Ten NDUFA13fl/- mice and 10 littermate control NDUFA13fl/fl mice were housed, and in each group, 5 mice were euthanized at the age of 4 weeks and the other 5 at two years for pathological examination of the liver tissues with HE staining. Immunohistochemistry was used to verify the expression levels of NDUFA13, NF-κB/p65, NF-κB/p-p65 and inflammasome NLRP3. The total intracellular ROS and mitochondrial ROS levels were measured with a ROS staining kit. The expressions of the inflammatory cell markers (CD45, MPO, and F4/80) and inflammatory cytokines (IL1ß and IL33) in the liver were detected with immunohistochemistry and immunofluorescence assay. RESULTS: Liver-specific NDUFA13 heterozygous knockout mice were successfully constructed as verified by PCR results. HE staining revealed severe liver damage in both 4- week-old and 2-year-old NDUFA13fl/- mice as compared with their littermate controls. Immunohistochemistry showed a significant decrease of NDUFA13 expression in both 4-week-old and 2-year-old NDUFA13fl/- mice (P < 0.05). The expression levels of NF-κB signals p65, p-p65 and NLRP3 inflammasomes were all significantly increased in NDUFA13fl/- mice (P < 0.05). The total intracellular ROS and mitochondrial ROS levels in NDUFA13fl/- mice were also significantly increased. NDUFA13 knockout obviously promoted the expression of the inflammatory cell markers (CD45, MPO and F4/80) and the secretion of IL-1ß and IL-33 in the liver tissue of the mice (P < 0.05). CONCLUSIONS: Hepatocytes-specific NDUFA13 ablation can trigger spontaneous hepatitis in mice possibly mediated by the activation of ROS/NF-κB/NLRP3 signaling.


Assuntos
Hepatite , Proteína 3 que Contém Domínio de Pirina da Família NLR , Animais , Inflamassomos , Camundongos , NF-kappa B/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Transdução de Sinais
18.
Biosci Trends ; 14(6): 450-456, 2021 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-33328394

RESUMO

Metabolic syndrome (MS) is common among obese people. Little is known about the magnitude and characteristics of MS in people living with HIV (PLWH) in Asian countries in general and China in particular. Using baseline data collected between February 2017 through January 2020 from the Comparative HIV and Aging Research in Taizhou (CHART) cohort in China, we examined MS among 2,227 PLWH and 5,264 matched people without HIV, respectively. MS was defined using the criteria set forth by the International Diabetes Federation (IDF). Approximately 76.7% of PLWH had body mass index (BMI) < 24.0 kg/m2, significantly higher than people without HIV (50.3%). Among participants with BMI < 24.0 kg/m2, PLWH had a significantly higher prevalence of MS than people without HIV (20.6% vs. 14.5%; aOR: 1.41, 95% CI: 1.19-1.68) overall, and at an age of 18-29 (10.4% vs. 3.4%, aOR: 3.49, 95% CI: 1.99-6.11) and 30-44 years (17.3% vs. 8.5%, aOR: 2.03, 95% CI: 1.47-2.81), respectively. Among participants with BMI ≥ 24.0 kg/m2, MS prevalence was not significantly different between PLWH and people without HIV overall, but significantly lower in PLWH than people without HIV for those aged over 60 years (65.9% vs. 77.8%, aOR: 0.53, 95% CI: 0.32-0.88). Among PLWH, MS was significantly associated with older age and higher CD4 cell count, and with stavudine (d4T) use only in the group of BMI < 24.0 kg/m2. Our finding is indicative of a relatively higher risk for early onset of MS among HIV-infected young adults with lower BMI. Research is needed to elucidate the pathogenic mechanism for MS among PLWH.

19.
AIDS Care ; : 1-5, 2020 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-33269606

RESUMO

Hypertension is highly prevalent among people living with HIV (PLWH). We sought to characterize the hypertension incidence among PLWH on antiretroviral therapy, focusing on the effect of change in general and abdominal obesity on hypertension during follow-up. This was a prospective analysis of 229 treated PLWH aged over 40 years without hypertension at baseline. Overall a median follow-up of 2.9 years, 26.2% PLWH developed hypertension. In multivariable models, compared to those without obesity measures at both baseline and follow-up visit, PLWH with general obesity at both occasions (adjusted odds ratio [aOR] = 3.83, P = 0.006) or at baseline only (aOR = 5.45, P = 0.003), abdominal obesity (measured as waist circumference) at both occasions (aOR = 3.87, P = 0.001) or at follow-up only (aOR = 2.27; 9P = 0.060), abdominal obesity (measured as waist-to-hip ratio) at both occasions (aOR = 2.27, P = 0.077) were at increased risk of incident hypertension. Our data show that both general and abdominal obesity especially in the persistent status increase the hypertension risk in treated PLWH.

20.
Front Psychol ; 11: 563493, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33192834

RESUMO

Block building is a popular play activity among young children and is also used by psychologists to assess their intelligence. However, little research has attempted to systematically explore the cognitive bases of block-building ability. The current study (N = 66 Chinese preschoolers, 32 boys and 34 girls; mean age = 4.7 years, SD = 0.29, range = 3.4 to 5.2 years) investigated the relationships between six measures of spatial skills (shape naming, shape recognition, shape composition, solid figure naming, cube transformation, and mental rotation, with the former four representing form perception and the latter two representing visualization) and block-building complexity. Correlation results showed that three of the four measures of form perception (shape naming, shape recognition, and shape composition) were significantly and positively correlated with block-building complexity, whereas the two measures of visualization were not. Results from regression models indicated that shape recognition and shape composition, as well as shape-recognition-by-gender interaction, were unique predictors of children's block-building complexity. These findings provide preliminary evidence for the basic spatial skills underlying children's block-building complexity and have implications for classroom instructions aimed at improving preschoolers' block-building complexity.

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