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1.
Trials ; 22(1): 713, 2021 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-34663424

RESUMO

BACKGROUND: Periarthritis of the shoulder is a common disease leading to dysfunction of the shoulder joint and have a significant impact on patients' daily life. Evidence shows that there is a close relationship between scapular dyskinesis (SD) and shoulder diseases. Scapular stabilization exercise has been proved to be efficacious in relieving pain and improving function. However, there is no targeted exercise based on the type of scapular dyskinesis. This study will investigate the potential of scapular stabilization exercise based on the type of scapular dyskinesis in treating periarthritis of the shoulder. METHODS: This study is a prospective, randomized controlled, parallel-group trial, intending to recruit 90 patients diagnosed with periarthritis of the shoulder. Patients will receive scapular stabilization exercise training based on the type of scapular dyskinesis or receive traditional rehabilitation training conducted for 30 min, once a day, for 6 weeks. The primary outcome is Constant-Murley score (CMS), and other outcomes include pain degree, range of motion (ROM), type of scapular dyskinesis, scapula position, and patients' satisfaction with shoulder function. Assessments will be performed at baseline, 2-, 4- and 6-week treatment, and at the 6-week follow-up after the end of treatment. DISCUSSION: This study will be the first study to investigate the clinical efficacy of scapular stabilization exercise based on the type of scapular dyskinesis in patients with periarthritis of the shoulder. The results may provide evidence of the effect of targeted scapular stabilization exercise in improving shoulder function and correcting scapular dyskinesis, and provide valuable information for future research. TRIAL REGISTRATION: This study had been registered in the Chinese Clinical Trials Registry. Registration number: ChiCTR2100044332 at March 14, 2021.

2.
Artigo em Inglês | MEDLINE | ID: mdl-34416676

RESUMO

A molecularly imprinted polymer (MIP) with magnetic carbon nanotubes (MCNTs) as carrier was synthesized and used for the enrichment and determination of ferulic acid (FA) by high-performance liquid chromatography (HPLC). The morphology and structure of the FA magnetic carbon nanotubes-molecularly imprinted polymers (MCNTs@FA-MIPs) were characterized by Fourier transform infrared spectroscopy, scanning electron microscopy, transmission electron microscopy, and X-ray diffraction. The results demonstrated that the prepared MCNTs@FA-MIPs had excellent magnetic properties and uniform appearance. The adsorption properties of the novel MIP were studied by kinetic, and isothermal adsorption experiments. The results showed that the MCNTs@FA-MIPs exhibited relatively good uptake kinetics (equilibrium time, 2 h), high adsorption capacity (50 mg⋅g-1), fast separation, and good selectivity for the template molecule with a separation factor α of 1.73. The MCNTs@FA-MIPs combined with HPLC were successfully applied to the separation, enrichment, and determination of FA in a Ligusticum chuanxiong extract and in plasma of rats which had been administered with Taitai beauty essence. The recoveries for FA were 95.53-100.03 % with relative standard deviations (RSDs) less than 5.5%. The results confirmed that the proposed MCNTs@FA-MIPs offered efficient extraction of FA from traditional Chinese medicinal preparations and blood samples and with high specificity.

3.
BMC Musculoskelet Disord ; 22(1): 686, 2021 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-34384393

RESUMO

BACKGROUND: Total two-stage exchange is commonly used in clinical practice as a treatment for infected total hip arthroplasty (THA); however, this approach involves considerable limitations, including significant bone loss and severe trauma. This retrospective cohort study was conducted to evaluate clinical outcomes following the use of partial two-stage exchange (PTE) for infected THA. METHODS: We performed a retrospective analysis of 28 patients with infected THA who were treated by PTE between September 2000 and June 2019. Eligibility for PTE was limited to patients with a well-fixed femoral stem prosthesis. In the first stage of the operation, the femoral stem prosthesis was preserved; subsequently, the acetabular prosthesis, liner, and head were replaced with an antibiotic-loaded spacer. The new prosthesis was then implanted into patients and monitored for at least 3 months to ensure freedom from infection. RESULTS: Patients were followed for an average of 4 years (range, 2-11 years), with an overall success rate of 85.7% (24/28). The mean Harris hip score at the final follow-up was 76.2 ± 11.7 points. CONCLUSIONS: The findings of this study suggest that PTE could be an acceptable option for a subset of patients with infected THA, offering a satisfactory infection control rate and clinical outcomes comparable to those of total two-stage exchange, but with less harm.


Assuntos
Artroplastia de Quadril , Prótese de Quadril , Infecções Relacionadas à Prótese , Artroplastia de Quadril/efeitos adversos , Prótese de Quadril/efeitos adversos , Humanos , Infecções Relacionadas à Prótese/diagnóstico , Infecções Relacionadas à Prótese/epidemiologia , Infecções Relacionadas à Prótese/cirurgia , Reoperação , Estudos Retrospectivos , Resultado do Tratamento
4.
Comput Biol Med ; 135: 104632, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34265554

RESUMO

Obstructive sleep apnea (OSA) is a serious sleep disorder, which leads to changes in autonomic nerve function and increases the risk of cardiovascular disease. Heart rate variability (HRV) has been widely used as a non-invasive method for assessing the autonomic nervous system (ANS). We proposed the two-dimensional sample entropy of the coarse-grained Gramian angular summation field image (CgSampEn2D) index. It is a new index for HRV analysis based on the temporal dependency complexity. In this study, we used 60 electrocardiogram (ECG) records from the Apnea-ECG database of PhysioNet (20 healthy records and 40 OSA records). These records were divided into 5-min segments. Compared with the classical indices low-to-high frequency power ratio (LF/HF) and sample entropy (SampEn), CgSampEn2D utilizes the correlation information between different time intervals in the RR sequences and preserves the temporal dependency of the RR sequences, which improves the OSA detection performance significantly. The OSA screening accuracy of CgSampEn2D (93.3%) is higher than that of LF/HF (80.0%) and SampEn (73.3%). Additionally, CgSampEn2D has a significant association with the apnea-hypopnea index (AHI) (R = -0.740, p = 0). CgSampEn2D reflects the complexity of the OSA autonomic nerve more comprehensively and provides a novel idea for the screening of OSA disease.


Assuntos
Apneia Obstrutiva do Sono , Sistema Nervoso Autônomo , Frequência Cardíaca , Humanos , Polissonografia , Análise de Sistemas
5.
Phytomedicine ; 90: 153644, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34274601

RESUMO

BACKGROUND: Nephrotic syndrome (NS) is a common nephropathy with a complex and diverse aetiology. Both Imperatae rhizoma and Hedyotis diffusa Willd. are herbs that are widely used as medicine and functional food. In traditional Chinese medicine theory, they are used as an herbal pair (HP) to treat inflammation-related diseases in the clinic, especially disorders of the kidney. PURPOSE: This study aimed to investigate the anti-inflammatory and hypolipidaemic effects of HP in an NS rat model and provide scientific data for its clinical application. METHODS: An NS model was established by two-dose injection of Sprague-Dawley rats with adriamycin. Seven groups, including the sham, model, HP treatment (0.25, 0.5 and 1.0 g/kg/d), prednisone (positive control, 5 mg/kg/d), and atorvastatin (positive control, 4 mg/kg/d) groups, were tested. The biochemical indexes of renal function and inflammatory cytokines were determined by ELISA kits and/or qPCR assays, and the crucial protein involved in the signalling pathway were subsequently tested by qPCR and/or Western blotting. Based on specific compounds identified by LC-Q-TOF-MS, network pharmacological study was carried out. RESULTS: The levels of BUN, Scr, Upro, UA, Alb, TC, TG, and LDL-C were significantly elevated in model rats. HP treatment for four weeks improved the renal function and the dyslipidaemia by decreasing the levels of all parameters, except BUN and Scr. HP treatment (0.5 and 1.0 g/kg/d) upregulated the expression of PPARγ, CYP7b1, and LDLR in the liver, while it down-regulated PCSK9, showing a regulatory effect on lipid metabolism disorder. The levels of TNF-α and IL-1ß in the plasma and the mRNA expression of TNF-α, IL-1ß, MCP-1, and TGF-ß1 in the kidney were decreased in HP groups, revealing its anti-inflammatory effect in NS rats. The HP exerted an alleviation effect on the inflammatory response through the NF-κB pathway by inhibiting the mRNA and protein expression of p50 and p65. There were 34 compounds identified or tentatively characterized in HP. In the network pharmacological study, PPARG(PPARγ), PCSK9, RELA(p65), and NF-κB1(p50) were the top 20 targets for HP, supporting the animal experimental results. CONCLUSION: HP exhibited protective effects on NS rats. These effects might be closely related to the inhibition of NF-κB and PCSK9-LDLR and activation of the PPARγ-CYP7B1 signalling pathways.


Assuntos
Anti-Inflamatórios , Medicamentos de Ervas Chinesas , Hedyotis , Hipolipemiantes/farmacologia , Síndrome Nefrótica , Animais , Anti-Inflamatórios/farmacologia , Família 7 do Citocromo P450 , Medicamentos de Ervas Chinesas/farmacologia , Hedyotis/química , NF-kappa B , Síndrome Nefrótica/tratamento farmacológico , Pró-Proteína Convertase 9 , Ratos , Ratos Sprague-Dawley , Esteroide Hidroxilases/uso terapêutico
6.
J Med Chem ; 64(14): 9943-9959, 2021 07 22.
Artigo em Inglês | MEDLINE | ID: mdl-34251816

RESUMO

Reported as two antirenal cell carcinoma (RCC) drug candidates, marine-derived compounds piericidin A (PA) and glucopiericidin A (GPA) exhibit hepatotoxicity in renal carcinoma xenograft mice. Proteomics and transcriptomics reveal the hepatotoxicity related with cholesterol disposition since RCC is characterized by cholesterol accumulation. PA/GPA aggravate hepatotoxicity in high-cholesterol diet (HCD)-fed mice while exhibiting no toxicity in chow diet-fed mice. High cholesterol accumulation in liver is liver X receptor (LXR)-mediated cytochrome P450 family 7 subfamily a member 1 (CYP7A1) depression and low-density lipoprotein receptor (LDLR) activation. The farnesoid X nuclear receptor (FXR) is also depressed with a downregulated target gene OSTα. Different from PA directly combined with LXRα as an inhibitor, GPA exists as a prodrug in the liver and exerts toxic effects due to transformation into PA. Surface plasmon resonance (SPR) and docking results of 17 piericidins illustrate that glycosides exert no LXRα binding activity. A longer survival time of GPA-treated mice indicates that further exploration in anti-RCC drug research should focus on reducing glycosides transformed into PA and concentrating in the kidney tumor rather than the liver for lowering the risk of hepatotoxicity.


Assuntos
Colesterol na Dieta/efeitos adversos , Colesterol/metabolismo , Dieta Hiperlipídica/efeitos adversos , Receptores X do Fígado/metabolismo , Pericardite/metabolismo , Animais , Relação Dose-Resposta a Droga , Células Hep G2 , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Estrutura Molecular , Pericardite/induzido quimicamente , Pericardite/patologia , Relação Estrutura-Atividade , Células Tumorais Cultivadas
7.
Food Funct ; 12(14): 6416-6431, 2021 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-34076000

RESUMO

Depression is an important global health issue that is associated with serious physical and mental health consequences. The field of nutritional psychiatry has generated observational and efficacy data supporting a role for healthy dietary patterns in depression. Here, we aim to evaluate the effects of high-fat diet (HFD) consumption on depressive-like behaviors. BALB/c mice were grouped randomly: control, chronic restraint stress (CRS), HFD and CRS + HFD groups. The depressive-like behavior was evaluated using behavioral tests. The serotonin content in murine brain tissue and blood lipid concentrations were detected by ELISA. The fatty acid content in the liver, adipose tissue of epididymis, brain tissue, and serum of mice was determined by gas chromatography (GC). Expression of the fatty acid synthesis pathway-related enzymes at the mRNA level was analyzed by qRT-PCR. The results indicated that a high-fat diet could promote depressive-like behavior. In comparison with regular feeding, concentrations of blood lipids were significantly changed in the HFD group. Correlation analysis implied that high-density lipoprotein cholesterol (HDL-c) and low-density lipoprotein cholesterol (LDL-c) were closely related to depressive-like behavior. Based on fatty acid analysis, the palmitoleic acid, linoleic acid, oleic acid, and arachidonic acid content was remarkably changed in mice with depressive-like behavior. In addition, acetyl-CoA carboxylase (ACC), stearoyl-CoA desaturase-1 (SCD1), fatty acid desaturase 1 (FADS1), and fatty acid desaturase 2 (FADS2) expression, which are involved in de novo fatty acid synthesis, desaturation of fatty acids, and arachidonic acid synthesis, were strengthened in HFD mice with depressive-like behavior. Therefore, we postulated that the disorder of lipid metabolism induced by HFD consumption accelerated the development of depressive-like behavior.

8.
Bioorg Chem ; 112: 104927, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33932772

RESUMO

Four new chromene derivatives, pestalotiochromenoic acids A - D (1, 2, 4, and 5), and two new chromone derivatives, pestalotiochromones A and B (6 and 7), were obtained from the marine alga-derived fungus Pestalotiopsis neglecta SCSIO41403, as well as a reported derivate named piperochromenoic acid (3) with its configuration determined for the first time. Their structures were determined by detailed nuclear magnetic resonance (NMR) and mass spectroscopic analyses, while the absolute configurations were established by theoretical NMR and electronic circular dichroism (ECD) calculation, including Mo2(OAc)4-induced ECD experiments. Those chromene and chromone derivatives displayed weak cytotoxicity, but showed obvious liver X receptors (LXRs) modulatory activities, by in vitro tests on the expression of LXRα, LXRß and theirtarget gene ABCA1, as well as in silico docking analysis. Moreover, the high binding affinities between pestalotiochromone A (6) and LXRα, revealed by surface plasmon resonance (SPR) with the dissociation equilibrium constant (KD) value of 6.2 µM, demonstrated 6 could act as a new potential LXR agonist.

9.
Food Chem ; 359: 129960, 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-33945987

RESUMO

The interaction between lipase and quercetin 3-rhamnoside was studied by fluorescence spectroscopy, enzyme kinetics, and molecular dynamics simulation. The results showed that quercetin 3-rhamnoside had a strong quenching effect on the intrinsic fluorescence of lipase. The binding constant decreased with increasing temperature, and the number of binding sites approached 1. Thermodynamic parameters indicated that hydrogen bonding and van der Waals forces are the dominant forces when the interaction occurs. Circular dichroism spectroscopy and infrared spectroscopy proved that the ligand perturbed the structure of lipase. Enzyme kinetics results showed that quercetin 3-rhamnoside inhibited lipase, and the inhibitory effect was dose-dependent. Molecular dynamics simulation further explained the interaction mechanism and inhibitory effect. This study confirmed the inhibitory effect of quercetin 3-rhamnoside on lipase explained their binding mechanism, which will contribute to guiding the development of fat-reducing functional foods.


Assuntos
Lipase/metabolismo , Quercetina/metabolismo , Sítios de Ligação , Fluorescência , Ligação de Hidrogênio , Lipase/química , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Ligação Proteica , Quercetina/química , Espectrometria de Fluorescência/métodos , Temperatura , Termodinâmica
10.
BMC Pulm Med ; 21(1): 182, 2021 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-34051779

RESUMO

BACKGROUND: Idiopathic pulmonary hemosiderosis (IPH) encompasses a rare and agnogenic group of diffuse alveolar capillary hemorrhagic diseases. Corticosteroid treatment is the globally preferred therapeutic strategy for IPH; however, it can cause immunodeficiency. Nocardia infection often occurs in immunocompromised patients and primarily involves the pleura and lungs. Herein, we describe a case of pediatric pulmonary Nocardia infection after the corticosteroid treatment of IPH. CASE PRESENTATION: A 7-year-old girl presented with chief complaints of pale complexion persisting for 1 year and a cough for 20 days. Abundant hemosiderin-laden macrophages were detected in the gastric juice, which supported the diagnosis of IPH. Uninterrupted doses of corticosteroids were administered during the last hospitalization. After nearly 2 months of corticosteroids therapy, the patient began to cough and produce a purulent sputum. Next-generation sequencing of the bronchoalveolar lavage fluid revealed Nocardia abscessus (N. abscessus) DNA. Linezolid was administered with good response, and the patient was discharged after 18 days of hospitalization. Her symptoms and pulmonary lesions had recovered, and the IPH appeared to be well-controlled with low dose of corticosteroids in follow-up. CONCLUSIONS: Nocardia infection should be considered in the differential diagnoses for IPH patients receiving corticosteroid therapy, especially in patients with poor response to conventional empirical antibiotic therapy. Next-generation sequencing of bronchoalveolar lavage fluid may be used to quickly identify the Nocardia. Sulfonamides or linezolid are effective for pediatric pulmonary Nocardia infection.

11.
Entropy (Basel) ; 23(3)2021 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-33668394

RESUMO

Obstructive sleep apnea (OSA) is associated with reduced heart rate variability (HRV) and autonomic nervous system dysfunction. Sample entropy (SampEn) is commonly used for regularity analysis. However, it has limitations in processing short-term segments of HRV signals due to the extreme dependence of its functional parameters. We used the nonparametric sample entropy (NPSampEn) as a novel index for short-term HRV analysis in the case of OSA. The manuscript included 60 6-h electrocardiogram recordings (20 healthy, 14 mild-moderate OSA, and 26 severe OSA) from the PhysioNet database. The NPSampEn value was compared with the SampEn value and frequency domain indices. The empirical results showed that NPSampEn could better differentiate the three groups (p < 0.01) than the ratio of low frequency power to high frequency power (LF/HF) and SampEn. Moreover, NPSampEn (83.3%) approached a higher OSA screening accuracy than the LF/HF (73.3%) and SampEn (68.3%). Compared with SampEn (|r| = 0.602, p < 0.05), NPSampEn (|r| = 0.756, p < 0.05) had a significantly stronger association with the apnea-hypopnea index (AHI). Hence, NPSampEn can fully overcome the influence of individual differences that are prevalent in biomedical signal processing, and might be useful in processing short-term segments of HRV signal.

12.
Cancer Cell Int ; 21(1): 103, 2021 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-33579299

RESUMO

PURPOSE: Glioma is the most prevalent malignant form of brain tumors, with a dismal prognosis. Currently, cancer immunotherapy has emerged as a revolutionary treatment for patients with advanced highly aggressive therapy-resistant tumors. However, there is no effective biomarker to reflect the response to immunotherapy in glioma patient so far. So we aim to assess the clinical predictive value of FCER1G in patients with glioma. METHODS: The expression level and correlation between clinical prognosis and FER1G levels were analyzed with the data from CGGA, TCGA, and GEO database. Univariate and multivariate cox regression model was built to predict the prognosis of glioma patients with multiple factors. Then the correlation between FCER1G with immune cell infiltration and activation was analyzed. At last, we predict the immunotherapeutic response in both high and low FCER1G expression subgroups. RESULTS: FCER1G was significantly higher in glioma with greater malignancy and predicted poor prognosis. In multivariate analysis, the hazard ratio of FCER1G expression (Low versus High) was 0.66 and 95 % CI is 0.54 to 0.79 (P < 0.001), whereas age (HR = 1.26, 95 % CI 1.04-1.52), grade (HR = 2.75, 95 % CI 2.06-3.68), tumor recurrence (HR = 2.17, 95 % CI 1.81-2.62), IDH mutant (HR = 2.46, 95 % CI 1.97-3.01) and chemotherapeutic status (HR = 1.4, 95 % CI 1.20-1.80) are also included. Furthermore, we illustrated that gene FCER1G stratified glioma cases into high and low FCER1G expression subgroups that demonstrated with distinct clinical outcomes and T cell activation. At last, we demonstrated that high FCER1G levels presented great immunotherapeutic response in glioma patients. CONCLUSIONS: This study demonstrated FCER1G as a novel predictor for clinical diagnosis, prognosis, and response to immunotherapy in glioma patient. Assess expression of FCER1G is a promising method to discover patients that may benefit from immunotherapy.

13.
Food Chem ; 347: 129052, 2021 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-33482484

RESUMO

Hyperoside (HYP) is an important natural product that is widely distributed in fruits and whole grasses of various plants. It is also used by consumers as a healthy ingredient. This work explored the interaction mechanisms between HYP and two main soy proteins, namely, ß-conglycinin (7S) and glycinin (11S), using computational simulation and multi-spectroscopic technology. In this study, the docking and dynamic simulation showed that HYP was stable in the hydrophobic pockets of the proteins. The conformation and microenvironment of 7S/11S also changed after binding to HYP. The binding of HYP to 7S/11S was a state quenching with a good affinity at 4 °C. This result was determined from the binding constant values of (1.995 ± 0.170) × 107 M-1 and (2.951 ± 0.109) × 107 M-1, respectively. The 7S/11S-HYP complex delineated here will provide a novel idea to construct an embedding and delivery system in improving the benefits of HYP for the development of high value-added food products.


Assuntos
Antígenos de Plantas/metabolismo , Globulinas/química , Globulinas/metabolismo , Quercetina/análogos & derivados , Proteínas de Armazenamento de Sementes/metabolismo , Proteínas de Soja/química , Proteínas de Soja/metabolismo , Soja/metabolismo , Antígenos de Plantas/química , Sítios de Ligação , Interações Hidrofóbicas e Hidrofílicas , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Quercetina/química , Quercetina/metabolismo , Proteínas de Armazenamento de Sementes/química , Soja/química , Termodinâmica
14.
J Chromatogr Sci ; 59(3): 212-216, 2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-33257934

RESUMO

Five non-polar phloroglucinol derivatives, viz. pseudo-aspidin, α-kosin and agripinol A-C were isolated and purified from Agrimonia pilosa Ledeb by semi-preparative counter-current chromatography. The separation was performed by a two-step elution with non-aqueous solvent systems. In the first step, an elution mode of a two-phase solvent system consisting of n-hexane-acetonitrile-dichloromethane-methanol (6:6:0.5:0.5, v/v/v/v) was used. We obtained sample Ι containing three components (47.0 mg) and sample ΙΙ containing two components (24.8 mg) from crude extract (371.0 mg). In the second step, sample Ι was successfully separated by closed-loop recycling mode with a solvent system consisting of n-hexane-acetonitrile-dichloromethane (10:7:3, v/v/v), yielding 17.8 mg of pseudo-aspidin, 18.5 mg of α-kosin and 6.4 mg of agripinol A. The other two compounds-8.7 mg of agripinol B and 13.6 mg of agripinol C-were obtained from sample ΙΙ in the same manner. All the isolated compounds had a high purity exceeding 95%.


Assuntos
Agrimonia/química , Distribuição Contracorrente/métodos , Floroglucinol , Isomerismo , Floroglucinol/análogos & derivados , Floroglucinol/análise , Floroglucinol/isolamento & purificação , Extratos Vegetais/química , Solventes/química
15.
Int Immunopharmacol ; 90: 107240, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33310663

RESUMO

Cytochrome P450 4F (CYP4F) enzymes are responsible for the metabolism of eicosanoids, which play important roles in inflammation. Nuclear receptor liver X receptor alpha (LXRα) is a critical signal node connecting inflammation and lipid metabolism. Studies revealed that the release of cytokines and nuclear factor-κB (NF-κB) can change the CYP4F11 expression in HepG2 cells. However, the effect of LXRα on the CYP4F family and the underlying mechanism remain unclear. This study found that CYP4F11 is a target gene of LXRα. Luciferase assays and siRNA transfection showed that LXRα increased the transcription of CYP4F11 and LXRα agonist GW3965 could induce the expression of CYP4F11 by activating the LXRα-CYP4F11 pathway. Besides, overexpression of CYP4F11 could decrease TNF-α and IL-1ß in lipopolysaccharide (LPS)-induced THP-1 cells. The finding of the regulation of CYP4F11 may contribute to the anti-inflammatory activity of LXRα agonists.


Assuntos
Família 4 do Citocromo P450/biossíntese , Regulação Enzimológica da Expressão Gênica/genética , Receptores X do Fígado/genética , Animais , Benzoatos/farmacologia , Benzilaminas/farmacologia , Família 4 do Citocromo P450/genética , Citocinas/metabolismo , Células HEK293 , Células Hep G2 , Humanos , Interleucina-1beta/biossíntese , Lipopolissacarídeos/farmacologia , Receptores X do Fígado/agonistas , Camundongos , Camundongos Endogâmicos C57BL , NF-kappa B , RNA Interferente Pequeno/genética , Transfecção , Fator de Necrose Tumoral alfa/biossíntese
16.
Drug Dev Res ; 82(4): 575-580, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33377532

RESUMO

Acute liver injury (ALI) is a serious syndrome that is associated with high mortality, but there are few effective treatments. The activation of NLRP3 inflammasome is associated with ALI. Oridonin is a natural substance with an anti-inflammatory effect and has been reported to be an inhibitor of NLRP3. The aim of this study was to investigate the protective effect of oridonin on d-galactosamine (d-GalN)/lipopolysaccharide (LPS)-induced ALI and whether the effect is mediated by NLRP3. Mice were pretreated with oridonin (5 or 10 mg/kg) for 3 days. Then, they were injected with d-GalN (400 mg/kg) and LPS (40 µg/kg). The levels of inflammatory factors were measured by RT-PCR, Western blot, and enzyme-linked immunosorbent assay. We confirmed that oridonin significantly alleviated ALI induced by d-GalN/LPS in mice. Oridonin markedly decreased the inflammatory response by reducing the levels of inflammatory cytokines. More importantly, oridonin markedly reduced the expression of NLRP3, caspase-1, IL-18, and IL-1ß. This study showed that oridonin has a protective effect on d-GalN/LPS-induced ALI, and the underlying mechanisms may be associated with the inhibition of the NLRP3 inflammatory pathways.

17.
Open Forum Infect Dis ; 7(8): ofaa314, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32875002

RESUMO

Major histocompatibility complex (MHC) II deficiency is a rare primary immunodeficiency disorder that is characterized by the deficiency of MHC class II molecules. The disease is caused by transcription factor mutations including class II transactivator (CIITA), regulatory factor X-5 (RFX5), RFX-associated protein (RFXAP), and RFXAP-containing ankyrin repeat (RFXANK), respectively. Mutations in the RFXANK gene account for >70% of all known patients worldwide. Herein, we reported a 10-month-old boy with MHC II deficiency caused by a novel mutation in the RFXANK gene (c.337 + 1G>C). The boy was admitted to the hospital due to pneumonia and diarrhea at 4 months of age. Genetic analysis revealed a novel homozygous mutation in the RFXANK gene, which derived from the c.337 + 1G>C heterozygous mutations in the RFXANK gene of his parents. The boy died 3 months after diagnosis. More than 200 cases have been reported, and a review of the literature revealed different mutation rates of 4 transcription factors in different countries or regions. This is the first case report of MHC II deficiency from East Asia. We also describe all gene mutations that cause MHC II deficiency and the epidemiology of MHC II deficiency with gene mutations in this paper.

18.
MAbs ; 12(1): 1802187, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32835602

RESUMO

SERINC5 is a multi-pass transmembrane protein that is thought to play a role in serine incorporation during cellular membrane biosynthesis. This protein has also been identified as a human immunodeficiency virus Type 1 (HIV-1) restriction factor. The paucity of monoclonal antibodies (mAbs) against SERINC5 has posed a challenge for the study of the endogenous protein. Here we report the development of novel anti-SERINC5 mAbs that target three distinct loops on the protein. We demonstrate that these SERINC5 mAbs can be used to detect endogenously expressed SERINC5 protein in various cell lines using Western blot, whole-cell ELISA, flow cytometry, and immunocytochemistry. We further show that some of these antibodies can detect SERINC5 that is present in HIV-1 viral stocks. These antibodies will aid in the characterization of the functions and mechanisms of action of SERINC5 in different cell types.

19.
J Clin Invest ; 130(10): 5235-5244, 2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-32634129

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent for coronavirus 2019 (COVID-19) pneumonia. Little is known about the kinetics, tissue distribution, cross-reactivity, and neutralization antibody response in patients with COVID-19. Two groups of patients with RT-PCR-confirmed COVID-19 were enrolled in this study: 12 severely ill patients in intensive care units who needed mechanical ventilation and 11 mildly ill patients in isolation wards. Serial clinical samples were collected for laboratory detection. Results showed that most of the severely ill patients had viral shedding in a variety of tissues for 20-40 days after onset of disease (8/12, 66.7%), while the majority of mildly ill patients had viral shedding restricted to the respiratory tract and had no detectable virus RNA 10 days after onset (9/11, 81.8%). Mildly ill patients showed significantly lower IgM response compared with that of the severe group. IgG responses were detected in most patients in both the severe and mild groups at 9 days after onset, and remained at a high level throughout the study. Antibodies cross-reactive to SARS-CoV and SARS-CoV-2 were detected in patients with COVID-19 but not in patients with MERS. High levels of neutralizing antibodies were induced after about 10 days after onset in both severely and mildly ill patients which were higher in the severe group. SARS-CoV-2 pseudotype neutralization test and focus reduction neutralization test with authentic virus showed consistent results. Sera from patients with COVID-19 inhibited SARS-CoV-2 entry. Sera from convalescent patients with SARS or Middle East respiratory syndrome (MERS) did not. Anti-SARS-CoV-2 S and N IgG levels exhibited a moderate correlation with neutralization titers in patients' plasma. This study improves our understanding of immune response in humans after SARS-CoV-2 infection.


Assuntos
Anticorpos Antivirais/sangue , Betacoronavirus/metabolismo , Infecções por Coronavirus/sangue , Pneumonia Viral/sangue , Carga Viral , Eliminação de Partículas Virais , Adulto , Idoso , Especificidade de Anticorpos , COVID-19 , Reações Cruzadas , Feminino , Humanos , Cinética , Masculino , Pessoa de Meia-Idade , Pandemias , SARS-CoV-2 , Índice de Gravidade de Doença
20.
J Cell Mol Med ; 24(18): 10444-10457, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32681612

RESUMO

Over-activated osteoclastogenesis, which is initiated by inflammation, has been implicated in osteoporosis. Corilagin, a natural compound extracted from various medicinal herbaceous plants, such as Cinnamomum cassia, has antioxidant and anti-inflammatory activities. We found that Corilagin suppressed osteoclast differentiation in a dose-dependent manner, significantly decreased osteoclast-related gene expression and impaired bone resorption by osteoclasts. Moreover, phosphorylation of members of the nuclear factor-kappaB (NF-κB) and PI3K/AKT signalling pathways was reduced by Corilagin. In a murine model of osteoporosis, Corilagin inhibited osteoclast functions in vivo and restored oestrogen deficiency-induced bone loss. In conclusion, our findings suggested that Corilagin inhibited osteoclastogenesis by down-regulating the NF-κB and PI3K/AKT signalling pathways, thus showing its potential possibility for the treatment of osteoporosis.


Assuntos
Reabsorção Óssea/patologia , Estrogênios/deficiência , Glucosídeos/farmacologia , Taninos Hidrolisáveis/farmacologia , NF-kappa B/metabolismo , Osteogênese/efeitos dos fármacos , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ligante RANK/farmacologia , Actinas/metabolismo , Animais , Células da Medula Óssea/efeitos dos fármacos , Células da Medula Óssea/metabolismo , Regulação para Baixo/efeitos dos fármacos , Glucosídeos/química , Taninos Hidrolisáveis/química , Camundongos , Camundongos Endogâmicos C57BL , Fatores de Transcrição NFATC/metabolismo , Osteoclastos/efeitos dos fármacos , Osteoclastos/metabolismo , Osteoclastos/patologia , Osteoprotegerina/metabolismo , Ovariectomia , Células RAW 264.7 , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos
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