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1.
Arch Biochem Biophys ; 758: 110078, 2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38944139

RESUMO

About 140 million people worldwide live at an altitude above 2500 m. Studies have showed an increase of the incidence of hyperuricemia among plateau populations, but little is known about the possible mechanisms. This study aims to assess the effects of high altitude on hyperuricemia and explore the corresponding mechanisms at the histological, inflammatory and molecular levels. This study finds that intermittent hypobaric hypoxia (IHH) exposure results in an increase of serum uric acid level and a decrease of uric acid clearance rate. Compared with the control group, the IHH group shows significant increases in hemoglobin concentration (HGB) and red blood cell counts (RBC), indicating that high altitude hyperuricemia is associated with polycythemia. This study also shows that IHH exposure induces oxidative stress, which causes the injury of liver and renal structures and functions. Additionally, altered expressions of organic anion transporter 1 (OAT1) and organic cation transporter 1 (OCT1) of kidney have been detected in the IHH exposed rats. The adenosine deaminase (ADA) expression levels and the xanthione oxidase (XOD) and ADA activity of liver of the IHH exposure group have significantly increased compared with those of the control group. Furthermore, the spleen coefficients, IL-2, IL-1ß and IL-8, have seen significant increases among the IHH exposure group. TLR/MyD88/NF-κB pathway is activated in the process of IHH induced inflammatory response in joints. Importantly, these results jointly show that IHH exposure causes hyperuricemia. IHH induced oxidative stress along with liver and kidney injury, unusual expression of the uric acid synthesis/excretion regulator and inflammatory response, thus suggesting a potential mechanism underlying IHH-induced hyperuricemia.

2.
Ear Nose Throat J ; : 1455613241261457, 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38877652

RESUMO

Pleomorphic adenoma (PA) represents the most frequently occurring benign tumor within both major and minor salivary glands. However, in rare instances, nasal PA is an epithelial-derived borderline tumor, often originating from the nasal septum. Diagnosis usually relies on histopathological analysis. Under general anesthesia, these rare nasal tumors can be completely resected via endoscopic surgery. This article reports a case of PA originating from the nasal septum in a 49-year-old patient presenting with nasal congestion, along with a brief review of the current literature. The diagnostic nasal endoscopic examination showed a pink neoplastic mass in the left nasal cavity. Subsequent radiologic examination demonstrated a soft tissue mass in the anterior part of the nasal septum. After complete resection under nasal endoscopy, histopathological examination confirmed it as PA. Fortunately, no related complications occurred perioperatively and postoperatively. After surgery, performing a thorough examination with nasal endoscopy and scheduling regular follow-ups are crucial steps to prevent local recurrence.

3.
Br J Haematol ; 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38831655

RESUMO

Chronic refractory primary immune thrombocytopenia (CRITP) is currently defined as refractory to multiple therapeutic of second-line agents with or without splenectomy, faced with the threat of severe bleeding and challenging to obtain effective treatment. Although stable and effective drug therapy is needed, it is tough to find one. Daratumumab (Dara), an anti-CD38 monoclonal antibody presented the target cloned plasma cells in multiple myeloma, has also been reported to be effective in refractory autoimmune cytopenia in some case or series reports and ongoing clinical trials for adult patients with CRITP. Here, we report the early and durable response of Dara combination with avatrombopag in three CRITP patients (2 male and 1 female aged 12, 5 and 7 years, respectively) in our centre, with a follow-up period of more than 25 weeks. Before Dara, the duration of immune thrombocytopenia was 9, 1.4 and 4 years, respectively, a baseline platelet count of 4, 6, 9 × 109/L, the bleeding score was all above level 2 and the number of previous drugs was >3. The time to response (R: Plt ≥30 × 109/L with at least a twofold increase in the baseline count) of Dara was on Day 45, 6 and 4 and achieved complete response (CR: Plt ≥100 × 109/L) on Day 51, 6 and 8, the sustained response (SR: Plt >30 × 109/L following Dara at ≥75% of the platelet count assessment at follow-up end-point since the patient achieved response) was 48, 175 and 204 days with the follow-up time of 39.1, 25.9 and 29.7 weeks. The bleeding score decreased from grade 3 to grade 0 during follow-up. No significant treatment-related adverse events were found during follow-up. Dara combination with avatrombopag may be a safe and efficacious therapy for children with CRITP, but it needs to be further explored.

4.
Pak J Pharm Sci ; 37(1): 139-145, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38741410

RESUMO

Liposomes, a nanoscale carrier, plays an important role in the delivery of drug, affects the in vivo efficacy of drugs. In this paper, silymarin(SM)-loaded liposomes was optimized using the response surface method (RSM), with entrapment efficiency (EE%) as an index. The formulation was optimized as follow: lecithin (7.8mg/mL), SM/lecithin (1/26) and lecithin/cholesterol (10/1). The optimized SM liposomes had a high EE (96.58 ±3.06%), with a particle size of 290.3 ±10.5nm and a zeta potential of +22.98 ±1.73mV. In vitro release tests revealed that SM was released in a sustained-release manner, primarily via diffusion mechanism. In vitro cytotoxicity studies demonstrated that the prepared SM liposomes had stronger inhibitory effects than the model drug. Overall, these results indicate that this liposome system is suitable for intravenous delivery to enhance the antitumor effects of SM.


Assuntos
Lecitinas , Lipossomos , Tamanho da Partícula , Silimarina , Silimarina/farmacologia , Silimarina/química , Silimarina/administração & dosagem , Humanos , Lecitinas/química , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/administração & dosagem , Liberação Controlada de Fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Colesterol/química , Química Farmacêutica , Composição de Medicamentos
5.
Br J Haematol ; 202(3): 636-644, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37188335

RESUMO

Immune thrombocytopenia (ITP) is an autoimmune bleeding disorder characterized by isolated thrombocytopenia and a haemorrhagic risk. Thrombopoietin receptor agonists (TPO-RAs) are highly effective for ITP and are widely used to treat patients with steroid treatment failure or dependency. However, although treatment response to TPO-RAs may differ according to the type, the potential impact of switching from eltrombopag (ELT) to avatrombopag (AVA) with respect to efficacy or tolerance in children remains unknown. This study aimed to evaluate the outcomes of switching from ELT to AVA in paediatric patients with ITP. We retrospectively evaluated children with chronic immune thrombocytopenia (cITP) switched from ELT to AVA owing to treatment failure at the Hematology-Oncology Center of Beijing Children's Hospital between July 2021 and May 2022. Overall, 11 children (seven and four boys and girls respectively) with a median age of 8.3 (range: 3.8-15.3) years were included. The overall response and complete response (platelet [PLT] count ≥100 × 109 /L) rates during AVA treatment were 81.8% (9/11) and 54.6% (6/11) respectively. The median PLT count was significantly increased from ELT to AVA (7 [range: 2-33] × 109 /L vs. 74 [15-387] × 109 /L; p = 0.007). The median time to PLT count ≥30 × 109 /L was 18 (range: 3-120) days. Overall, 7/11 patients (63.6%) used concomitant medications, and concomitant medication use was gradually discontinued within 3-6 months after AVA initiation. In conclusion, AVA after ELT is effective in the heavily pretreated paediatric cITP population, with high response rates even in those with an inadequate response to a prior TPO-RA.


Assuntos
Púrpura Trombocitopênica Idiopática , Trombocitopenia , Masculino , Feminino , Humanos , Criança , Pré-Escolar , Adolescente , Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Estudos Retrospectivos , Trombocitopenia/tratamento farmacológico , Benzoatos/uso terapêutico , Hidrazinas/uso terapêutico , Falha de Tratamento , Trombopoetina/uso terapêutico , Proteínas Recombinantes de Fusão/uso terapêutico
7.
Front Plant Sci ; 13: 956083, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36299788

RESUMO

Physalins, active ingredients from the Physalis alkekengi L. var. franchetii (P. alkekengi) plant, have shown anti-inflammatory, antioxidant and anticancer activities. Whereas the bioactivity of physalins have been confirmed, their biosynthetic pathways, and those of quite a few derivatives, remain unknown. In this paper, biosynthesis and structure modification-related genes of physalins were mined through transcriptomic and metabolomic profiling. Firstly, we rapidly and conveniently analyzed physalins by UPLC-Q-TOF-MS/MS utilizing mass accuracy, diagnostic fragment ions, and common neutral losses. In all, 58 different physalin metabolites were isolated from P. alkekengi calyxes and berries. In an analysis of the physalin biosynthesis pathway, we determined that withanolides and withaphysalins may represent a crucial intermediate between lanosterol and physalins. and those steps were decanted according to previous reports. Our results provide valuable information on the physalin metabolites and the candidate enzymes involved in the physalins biosynthesis pathways of P. alkekengi. In addition, we further analyzed differential metabolites collected from calyxes in the Jilin (Daodi of P. alkekengi) and others. Among them, 20 physalin metabolites may represent herb quality biomarkers for Daodi P. alkekengi, providing an essential role in directing the quality control index of P. alkekengi.

8.
Pharmacology ; 107(5-6): 281-289, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35325888

RESUMO

AIM: Recent evidence indicates that neuroinflammation and oxidative stress play vital roles in the pathological process of major depressive disorder (MDD). Cinnamic acid (CA), a naturally occurring organic acid, has been reported to ameliorate neuroinflammation and oxidative stress for treatment of diabetes-related memory deficits. Here, we explored whether CA pretreatment ameliorated lipopolysaccharide (LPS)-induced depressive-like behaviors in mice by suppressing neuroinflammation and by improving oxidative stress status. METHODS: The mice were treated with CA, vehicle, or fluoxetine as a positive control. After 14 days, LPS (1 mg/kg, i.p.) or saline was administered. The depression-like behaviors were examined by the sucrose preference test (SPT), the forced swimming test (FST), and the tail suspension test (TST). Furthermore, the levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), superoxide dismutase (SOD), glutathione (GSH), malondialdehyde (MDA), and brain-derived neurotrophic factor (BDNF) in the hippocampus and cortex of mice were assayed. RESULTS: Our results demonstrated that CA pretreatment at the doses of 100 and 200 mg/kg significantly attenuated depressive-like behaviors in the TST, FST, and SPT. In addition, not only the upregulation of pro-inflammatory cytokines (IL-6 and TNF-α) but also oxidative stress parameters including SOD, GSH, and MDA in the hippocampus and cortex of mice treated with LPS were dramatically improved by CA pretreatment. Finally, CA pretreatment strikingly ameliorated the downregulation of BDNF induced by LPS in the hippocampus and cortex of mice. CONCLUSION: Our results indicated that CA may have therapeutic potential for MDD treatment through attenuating the LPS-induced inflammation and oxidative stress along with significant improvement of BDNF impairment.


Assuntos
Transtorno Depressivo Maior , Lipopolissacarídeos , Animais , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Cinamatos , Depressão/induzido quimicamente , Depressão/tratamento farmacológico , Glutationa/metabolismo , Hipocampo/metabolismo , Interleucina-6/metabolismo , Lipopolissacarídeos/toxicidade , Camundongos , Doenças Neuroinflamatórias , Estresse Oxidativo , Superóxido Dismutase , Fator de Necrose Tumoral alfa/metabolismo
9.
Expert Rev Clin Pharmacol ; 15(3): 365-369, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35212597

RESUMO

OBJECTIVE: This research aimed to assess the effect of Wuzhi capsules (WZC) on the blood concentration of cyclosporine A (CsA) in renal aplastic anemia recipients. METHODS: This observational study was carried out at the Hematology Oncology Center, Beijing Children's Hospital between November 2019 and February 2020. A total of 102 Chinese AA recipients receiving CsA (6 mg/kg/d) with or without WZC were included in this study. Baseline data, such as age, therapeutic drug monitoring data, and follow-up information were collected. The promotion concentration of CsA was calculated, and the pharmaceutical economics evaluation with combination of two drugs was also carried out. RESULTS: Dose- and body weight-adjusted trough concentrations (C0/D/W) of CsA in the WZC group were found to be significantly higher than that in the non-WZC group (P < 0.01). The average C0 of CsA increased by (63.27 ± 45.81) ng/mL. The incidence of adverse events was also not statistically significant between the two groups (P > 0.05). CONCLUSION: WZC can increase CsA concentration without increasing adverse drug reactions. Efficient and convenient immunosuppressive effects on AA recipients can be achieved via immunosuppressant therapy in combination with WZC.


Assuntos
Anemia Aplástica , Ciclosporina , Anemia Aplástica/tratamento farmacológico , Cápsulas , Criança , Ciclosporina/efeitos adversos , Medicamentos de Ervas Chinesas , Humanos , Fatores Imunológicos , Imunossupressores/efeitos adversos , Imunoterapia
11.
Immunol Invest ; 51(3): 619-629, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33739224

RESUMO

BACKGROUND: This study explored the correlation between the interleukin-1ß gene rs16944 polymorphism and diabetes through epidemiological and follow-up investigations. METHODS: The study was conducted on 600 subjects with normal glucose metabolism recruited from participants of the Risk Evaluation of cAncers in Chinese type 2 diabeTic Individuals: A lONgitudinal (REACTION) study in Luzhou, China in 2011. All subjects received a unified standardized questionnaire, physical examination, laboratory examination, and follow-up in 2016. Subjects were divided into normal glucose metabolism (NC), pre-diabetes (PDM), and type 2 diabetes mellitus (T2DM) groups according to their glucose metabolism after follow-up. The IL-1ß gene rs16944 polymorphism was analyzed using the polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP) technique. RESULTS: After follow-up, 386, 156, and 58 cases were observed in the NC, PDM, and T2DM groups, respectively. Serum IL-1ß levels were compared to baselines at follow-up in the 3 groups; the difference in the T2DM group was statistically significant. The frequency distributions of the IL-1ß gene rs16944 genotypes, i.e., CC, CT, and TT, were significantly different in the 3 groups, and the distributions in the T2DM and NC groups were significantly different. The frequency distributions of the C and T alleles of IL-1ß rs16944 were not significantly different. Logistic regression analysis identified the CC+CT genotype as an independent risk factor for the development of diabetes in patients with normal glucose metabolism (OR = 2.457, 95% CI: 1.238-4.877). CONCLUSIONS: The IL-1ß gene rs16944 C/T polymorphism may cause genetic susceptibility to T2DM in the Luzhou population. The CC+CT genotypes may increase T2DM risk.


Assuntos
Diabetes Mellitus Tipo 2 , Estudos de Casos e Controles , Estudos de Coortes , Diabetes Mellitus Tipo 2/genética , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Glucose , Humanos , Interleucina-1beta/genética , Polimorfismo de Nucleotídeo Único
12.
Blood Adv ; 5(19): 3799-3806, 2021 10 12.
Artigo em Inglês | MEDLINE | ID: mdl-34605871

RESUMO

Immune thrombocytopenia (ITP) is an autoimmune bleeding disorder with isolated thrombocytopenia and risk of hemorrhage. Treatment with eltrombopag increases and maintains hemostatic platelet counts; however, to date, long-term data are lacking on the outcome of children with ITP who are treated with eltrombopag. This prospective, observational, longitudinal cohort study evaluated the efficacy and safety of eltrombopag in pediatric patients with persistent or chronic ITP. For the 116 pediatric patients enrolled, duration of eltrombopag treatment was at least 3 months. Median effective dose was 25 mg/day, 50 mg/day, and 50 mg/day, respectively, for children age 5 years or younger, 6 to 11 years, or 12 years or older. In all, 89 patients (76.7%) achieved overall response, 53 (45.7%) achieved complete response, and 36 (31.0%) achieved response. Median platelet counts increased by week 1 and were sustained throughout the treatment period. During treatment with eltrombopag, the proportion of patients with grade 1 to 4 bleeding symptoms decreased from 83.61% at baseline to 9.88% at 6 months when only grade 1 was reported. Forty-three patients (37.1%) reported using concomitant medications at study entry, which was reduced to 1 patient (2.5%) who needed concomitant medications at 12 months. All adverse events were grade 1 or 2 according to Common Terminology Criteria for Adverse Events. No serious adverse events, cataracts, malignancies, or thromboses were reported during the study. Long-term treatment with eltrombopag was generally safe, well tolerated, and effective in maintaining platelet counts and reducing bleeding in most pediatric patients with persistent or chronic ITP. Combined with future studies, these findings will help establish how eltrombopag should best be used in the management of pediatric patients with East Asian ancestry.


Assuntos
Púrpura Trombocitopênica Idiopática , Trombocitopenia , Benzoatos/efeitos adversos , Criança , Pré-Escolar , China , Humanos , Hidrazinas , Estudos Longitudinais , Estudos Prospectivos , Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Pirazóis , Resultado do Tratamento
13.
Pediatr Hematol Oncol ; 38(7): 647-657, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33798022

RESUMO

Eltrombopag is being investigated for the treatment of aplastic anemia (AA) by stimulating hematopoietic stem cell (HSC) proliferation. To evaluate the efficacy and safety of eltrombopag in the first-line therapy of pediatric AA. The present retrospective study assessed pediatric patients with newly diagnosed AA administered immunosuppressive therapy (IST) (rabbit ATG combined with CSA) with eltrombopag at a single center from March to September 2017. All patients were followed up for >2 years. A total of 14 patients (8 males), averagely aged 86 months, were enrolled in this study. Eltrombopag was administered with a median time to initiation of 19.5 days after IST; the median course of treatment was 253 days. Complete and overall response rates at 6 months were 64.3% (9/14 case) and 78.6% (11/14 cases), respectively. The survival rate was 100%, and no relapse occurred in responders. Eltrombopag was well-tolerated; however, the most common adverse events included indirect bilirubin elevation, jaundice, and transient liver-enzyme elevation. By the end of follow-up, bone marrow chromosomes were normal, and no abnormal myelodysplastic syndrome (MDS)-related clones appeared. Addition of eltrombopag to IST is associated with markedly increased complete response with respect to hematology in pediatric patients with SAA compared with a historical cohort, without intolerable side effects.


Assuntos
Anemia Aplástica , Benzoatos/uso terapêutico , Hidrazinas/uso terapêutico , Imunossupressores/uso terapêutico , Pirazóis/uso terapêutico , Anemia Aplástica/tratamento farmacológico , Animais , Soro Antilinfocitário/uso terapêutico , Benzoatos/efeitos adversos , Criança , Ciclosporina/uso terapêutico , Feminino , Humanos , Hidrazinas/efeitos adversos , Imunossupressores/efeitos adversos , Masculino , Pirazóis/efeitos adversos , Coelhos , Estudos Retrospectivos , Resultado do Tratamento
14.
Zhongguo Zhong Yao Za Zhi ; 45(16): 3852-3856, 2020 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-32893580

RESUMO

The components of traditional Chinese medicine(TCMCs) are the basic unit of raw materials for Chinese medicines, and their physical and chemical properties directly affect the choice of dosage forms and the optimization of prescriptions. However, most of TCMCs are multi-component complex systems, and the characterization of their overall properties is still in the exploration stage. On the basis of biological activity, the representative components are determined, and then the individual characteristics are fitted with the weight coefficient of efficacy contribution rate, which may provide reference for characterizing the overall properties of TCMCs. In this study, with the pharmacological effects of isoproterenol(ISO)-induced myocardial ischemia in rats as the indicators, the pharmacodynamic contribution rates of three representative components of chishao terpene glucoside components(CSTGCs) were evaluated by the normalization weighting method. The contribution rates of paeoniflorin, paeoniflorin and benzoylpaeoniflorin were 54.87%, 32.46% and 12.67%, respectively. The oil-water partition coefficients of paeoniflorin, albiflorin, benzoylpaeoniflorin in water and buffer solutions with different pH values were measured, and the oil-water partition coefficients of CSTGCs were characterized by the weight of their pharmacodynamics contribution rate. The results showed that the apparent oil-water partition coefficient(log P) of CSTGCs in the phosphate buffer system such as n-octanol-water(pH 2.0, 2.5, 5.0, 5.8, 6.8) were 0.18-0.22, indicating that CSTGCs have common absorption and low permeability, providing basis for the preparation of CSTGCs.


Assuntos
Doença da Artéria Coronariana , Isquemia Miocárdica , Animais , Glucosídeos , Medicina Tradicional Chinesa , Ratos , Terpenos , Água
15.
Postgrad Med ; 132(8): 720-726, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32757691

RESUMO

OBJECTIVES: This study aimed to investigate the relationships among islet function, the Nrf2 pathway, and insulin receptor substrate 2 (IRS2) in type 2 diabetes mellitus (T2DM), prediabetes mellitus (IGR), and normal glucose tolerance (NGT) populations. METHODS: Three hundred cases each were selected for the NGT, IGR, and T2DM groups; FBG, 2hPG, HbA1 c, FINS, TG, TC, HDL-C, and LDL-C levels and serum levels of nuclear factor in E2-related factor 2 (Nrf2), insulin receptor substrate 2 (IRS2), tumor necrosis factor alpha (TNF-α), and heme oxygenase 1 (HO-1) were evaluated. RESULTS: The T2DM group had lower islet ß-cell function index and insulin sensitivity index than the NGT and IGR groups (P < 0.05). The Nrf2, IRS2, and HO-1 levels in the NGT, IGR, and T2DM groups followed a decreasing trend in the order mentioned, whereas the TNF-α levels followed an increasing trend. CONCLUSIONS: Upon impairment of glucose regulation, the expression of TNF-α in the human body increased, which indicated the aggravation of oxidative stress (OS) and the inflammatory response. Islet function was maintained in the pre-diabetic population, and concurrently, the TNF-α, Nrf2, and HO-1 levels were moderately elevated, the expression of IRS2 was marginally inhibited, and the Nrf2 pathway was activated under mild OS stimulus to resist OS, inflammation, and injury, which may have been mediated through PI3 K/AKT. In patients with T2DM, islet function was significantly poorer, TNF-α amplification was enhanced significantly, and Nrf2, HO-1, and IRS2 expression reduced significantly; this suggested that, along with the aggravation of OS and the inflammatory response, Nrf2 pathway activation and HO-1 expression were both inhibited, the antioxidant capacity of the body was reduced, IRS2 degradation increased, and islet function was impaired.


Assuntos
Diabetes Mellitus Tipo 2/fisiopatologia , Proteínas Substratos do Receptor de Insulina/metabolismo , Células Secretoras de Insulina/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Idoso , Glicemia , Pressão Sanguínea , Pesos e Medidas Corporais , Estudos Transversais , Feminino , Hemoglobinas Glicadas , Heme Oxigenase-1/biossíntese , Humanos , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Estado Pré-Diabético/fisiopatologia , Fator de Necrose Tumoral alfa/biossíntese
16.
Angew Chem Int Ed Engl ; 59(41): 17864-17871, 2020 10 05.
Artigo em Inglês | MEDLINE | ID: mdl-32602223

RESUMO

The visualization of temporal and spatial changes in the intracellular environment has great significance for chemistry and bioscience research. Mass spectrometry imaging (MSI) plays an important role because of its unique advantages, such as being label-free and high throughput, yet it is a challenge for laser-based techniques due to limited lateral resolution. Here, we develop a simple, reliable, and economic nanoscale MSI approach by introducing desorption laser with a micro-lensed fiber. Using this integrated platform, we achieved 300 nm resolution MSI and successfully visualized the distribution of various small-molecule drugs in subcellular locations. Exhaustive dynamic processes of anticancer drugs, including releasing from nanoparticle carriers entering nucleus of cells, can be readily acquired on an organelle scale. Considering the simplicity and universality of this nanoscale desorption device, it could be easily adapted to most of laser-based mass spectrometry applications.


Assuntos
Espectrometria de Massas/métodos , Preparações Farmacêuticas/metabolismo , Frações Subcelulares/metabolismo , Lasers
17.
Biochem Biophys Res Commun ; 524(2): 308-316, 2020 04 02.
Artigo em Inglês | MEDLINE | ID: mdl-31987499

RESUMO

BACKGROUND: Atherosclerotic plaque rupture is the major trigger of acute cardiovascular risk events, and manipulation of M1/M2 macrophage homeostasis is an effective strategy for regulating atherosclerotic plaque stability. This study was aimed to illuminate the effects of oleoylethanolamide (OEA) on macrophage polarization and plaque stability. METHODS: Macrophages derived from THP-1 were treated with OEA followed by LPS/IFN-γ, and the markers of M1, M2 macrophages were monitored by western blot, real-time PCR and immunofluorescence staining. The effect of OEA on macrophage polarization in the arch of aortic arteries was tested by immunofluorescence staining and western blot, and the plaque stability was completed by Masson's trichrome and hematoxylin and eosin (HE) in apolipoprotein E (ApoE)-/- mice. RESULTS: OEA treatment enhanced the expression of two classic M2 macrophage markers, macrophage mannose receptor (CD206) and transforming growth factor (TGF-ß), while the expression of iNOS (M1 macrophages) was decreased in THP-1-derived macrophages. Blocking of PPARα using siRNA and inhibition of AMP-activated protein kinase (AMPK) by its inhibitor compound C attenuated the OEA-induced expression of M2 macrophage markers. In addition, OEA significantly suppressed M1, promoted M2 macrophage polarization, increased collagen content and decreased necrotic core size in atherosclerotic plaques in ApoE-/- mice, which were linked with the expression of PPARα. CONCLUSIONS: OEA improved atherosclerotic plaque stability through regulating macrophage polarization via AMPK-PPARα pathway.


Assuntos
Proteínas Quinases Ativadas por AMP/imunologia , Anti-Inflamatórios/uso terapêutico , Endocanabinoides/uso terapêutico , Macrófagos/efeitos dos fármacos , Ácidos Oleicos/uso terapêutico , PPAR alfa/imunologia , Placa Aterosclerótica/tratamento farmacológico , Animais , Humanos , Ativação de Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Macrófagos/patologia , Masculino , Camundongos , Placa Aterosclerótica/imunologia , Placa Aterosclerótica/patologia , Transdução de Sinais/efeitos dos fármacos , Células THP-1
18.
Int J Immunopathol Pharmacol ; 33: 2058738419872120, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31438744

RESUMO

The treatment of severe chronic immune thrombocytopenia (SCITP) in pediatric patients is challenging. We evaluated the clinical efficacy and safety of eltrombopag in children with SCITP in China. This observational study was carried out at the Hematology Oncology Center, Beijing Children's Hospital between April 2017 and July 2018. Patients with SCITP who had at least 12 weeks of eltrombopag treatment and follow-up data were included. Baseline data, such as age, drug dosage, pre-study platelet count, concomitant medications, and bleeding severity, were collected. Treatment response rates, durable response rates, bleeding events, and adverse events were assessed during eltrombopag therapy for at least 12 weeks. The median duration of eltrombopag therapy was 16 (12-48) weeks. The overall, complete, and partial response rates were 75% (15/20), 35% (7/20), and 40% (8/20), respectively. The durable response rate was 70% (14/20). No serious bleeding events or serious adverse events occurred during the study period. Eltrombopag appears to be effective and safe in children with SCITP, although additional research is needed to confirm this.


Assuntos
Benzoatos/efeitos adversos , Benzoatos/uso terapêutico , Doença Crônica/tratamento farmacológico , Hidrazinas/efeitos adversos , Hidrazinas/uso terapêutico , Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Pirazóis/efeitos adversos , Pirazóis/uso terapêutico , Adolescente , Criança , Pré-Escolar , China , Feminino , Humanos , Lactente , Masculino , Contagem de Plaquetas/métodos , Resultado do Tratamento
19.
Int J Cardiovasc Imaging ; 35(8): 1499-1508, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31037475

RESUMO

Resting two-dimensional speckle tracking echocardiography (2D-STE) identified right ventricular (RV) systolic function were reported to predict exercise capacity in pulmonary hypertension (PH) patients, but little attention had been payed to 2D-STE detected RV diastolic function. Therefore, we aim to elucidate and compare the relations between 2D-STE identified RV diastolic/systolic functions and peak oxygen consumption (PVO2) determined by cardiopulmonary exercise testing (CPET) in pre-capillary PH. 2D-STE was performed in 66 pre-capillary PH patients and 28 healthy controls. Linear correlation and multivariate regression analyses were performed to evaluate and compare the relations between RV 2D-STE parameters and PVO2. Receiver operating characteristic curves were used to compare the predictive value of 2D-STE parameters in predicting the cut-off-PVO2 < 11 ml/min/kg. There were significant differences of all the 2D-STE parameters between PH patients and healthy controls. In patients, RV-peak global longitudinal strain (GLS, rs = - 0.498, P < 0.001), RV- peak systolic strain rate (GSRs, rs = - 0.537, P < 0.001) and RV- peak early diastolic strain rate (GSRe, rs = 0.527, P < 0.001) significantly correlated with PVO2, but no significant correlation was observed between RV- peak late diastolic strain rate (GSRa, rs = 0.208, P = 0.093) and PVO2. The first multivariate regression analysis of clinical data without echocardiographic parameters identified WHO functional class, NT-proBNP and BMI as independent predictors of PVO2 (Model-1, adjusted r2 = 0.421, P < 0.001); Then we added conventional echocardiographic parameters and 2D-STE parameters to the clinical data, identified S,(Model-2,adjusted r2 = 0.502, P < 0.001), RV-GLS (Model-3, adjusted r2 = 0.491, P < 0.001), RV-GSRe (Model-4, adjusted r2 = 0.500, P < 0.001) and RV-GSRs (Model-5, adjusted r2 = 0.519, P < 0.001) as independent predictors of PVO2, respectively. The predictive power was increased, and Model-5 including RV-GSRs showed the highest predictive capability. ROC curves found RV-GSRs expressed the strongest predictive value (AUC = 0.88, P < 0.001), and RV-GSRs > - 0.65/s had a 88.2% sensibility and 82.2% specificity to predict PVO2 < 11 ml/min/kg. 2D-STE assessed RV function improves the prediction of exercise capacity represented by PVO2 in pre-capillary PH.


Assuntos
Ecocardiografia Doppler/métodos , Tolerância ao Exercício , Hipertensão Pulmonar/diagnóstico por imagem , Função Ventricular Direita , Adulto , Estudos de Casos e Controles , Estudos Transversais , Teste de Esforço , Feminino , Humanos , Hipertensão Pulmonar/fisiopatologia , Masculino , Pessoa de Meia-Idade , Consumo de Oxigênio , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Adulto Jovem
20.
Clin Interv Aging ; 14: 445-451, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30880926

RESUMO

AIM: The aim of this study was to determine the relationship between abnormal glucose metabolism and osteoporosis (OP) in Han Chinese men over the age of 50 years. PATIENTS AND METHODS: A cross-sectional study of 775 male patients aged over 50 years was performed at our hospital in 2011. The patients were divided into a normal glucose metabolism group, an impaired glucose regulation (IGR) group, and a type 2 diabetes mellitus (T2DM) group. Differences in their bone mineral densities (BMDs), OP detection rates, and indices of bone metabolism were assessed. RESULTS: After adjusting for age and body mass index (BMI), there were no significant differences in lumbar spine, femoral neck, and total hip BMD values in the three groups (P>0.05) nor in OP detection rates (P=0.19). However, there were some significant differences in bone metabolism markers between the groups after adjusting for age, BMI, and serum creatinine (Cr): 25-hydroxyvitamin D (25(OH)D) was positively correlated with the presence of abnormal glycometabolism (r=0.08; P<0.01), while ß-carboxy-terminal cross-linking telopeptide of type I collagen (ß-CTX), bone gamma-carboxyglutamic acid protein (BGP; osteocalcin [OC]), and procollagen type 1 intact N-terminal propeptide (P1NP) were negatively correlated (r=-0.13, -0.21, -0.14, respectively; P<0.01). Logistic regression analysis of the data indicated that BGP was the only bone metabolism marker significantly influenced by abnormal glucose metabolism (OR =0.96). CONCLUSION: There were no significant differences in BMD or OP detection rates between the three glycometabolism groups after adjusting for age and BMI. However, the bone metabolism marker, BGP, was significantly negatively correlated with abnormal glucose metabolism.


Assuntos
Diabetes Mellitus Tipo 2/sangue , Glucose/metabolismo , Osteoporose/sangue , Osteoporose/diagnóstico por imagem , Idoso , Idoso de 80 Anos ou mais , Povo Asiático , Densidade Óssea , China , Colágeno Tipo I/sangue , Estudos Transversais , Diabetes Mellitus Tipo 2/complicações , Colo do Fêmur/diagnóstico por imagem , Humanos , Vértebras Lombares/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Osteocalcina/sangue , Osteoporose/complicações , Fragmentos de Peptídeos/sangue , Peptídeos/sangue , Pró-Colágeno/sangue , Vitamina D/análogos & derivados , Vitamina D/sangue
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