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1.
Nutrients ; 15(2)2023 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-36678288

RESUMO

Mannuronate oligosaccharide (MOS) is α-D-mannuronic acid polymer with 1,4-glycosidic linkages that possesses beneficial biological properties. The aim of this study was to investigate the hypouricemic effect of MOS in hyperuricemic mice and demonstrate the possible protective mechanisms involved. In this research, 200 mg/kg/day of MOS was orally administered to hyperuricemic mice for four weeks. The results showed that the MOS treatment significantly reduced the serum uric acid (SUA) level from 176.4 ± 7.9 µmol/L to 135.7 ± 10.9 µmol/L (p < 0.05). MOS alleviated the inflammatory response in the kidney. Moreover, MOS promoted uric acid excretion by regulating the protein levels of renal GLUT9, URAT1 and intestinal GLUT9, ABCG2. MOS modulated the gut microbiota in hyperuricemic mice and decreased the levels of Tyzzerella. In addition, research using antibiotic-induced pseudo-sterile mice demonstrated that the gut microbiota played a crucial role in reducing elevated serum uric acid of MOS in mice. In conclusion, MOS may be a potential candidate for alleviating HUA symptoms and regulating gut microbiota.


Assuntos
Microbioma Gastrointestinal , Hiperuricemia , Camundongos , Animais , Ácido Úrico , Rim/metabolismo , Nitrogênio da Ureia Sanguínea
2.
J Transl Med ; 21(1): 39, 2023 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-36681819

RESUMO

BACKGROUND: Different metabolic phenotypes may be related to nonalcoholic fatty liver disease (NAFLD), but such association whether modified by serum uric acid levels is unknown. We examined the association between different metabolic phenotypes and NAFLD and further explore whether hyperuricemia could modify this association. METHODS: A total of 2959 participants (mean age: 55.02 years) with medical checkups were recruited from Tianjin Medical University General Hospital. Participants were categorized into four groups according to their BMI levels and metabolically healthy status: metabolically healthy normal weight (MHNW), metabolically healthy overweight or obese (MHO), metabolically unhealthy normal weight (MUNW), and metabolically unhealthy overweight or obese (MUO). Blood samples (including serum uric acid) were collected from participants after an overnight fast. NAFLD was diagnosed based on abdominal ultrasonography scanning. Data were analyzed using logistic regression models and the interaction effect model. RESULTS: The prevalence of NAFLD in MHNW, MHO, MUNW, and MUO groups was 9.9% (7.9-12.0%), 42.8% (39.5-46.1%), 36.5% (31.2-41.9%), and 69.7% (66.8-72.6%), respectively. In multi-adjusted logistic models, the ORs (95% CIs) of NAFLD were 5.32 (4.01-7.04) for participants with MHO, 4.51 (3.17-6.40) for those with MUNW, and 13.68 (10.23-18.30) for those with MUO compared to those with MHNW. In the stratified analysis by uric acid levels, the prevalence of NAFLD was significantly higher in participants with MHO, MUNW, and MUO in the hyperuricemia group than those in the normal uric acid group, and the interaction effect of metabolic phenotypes and uric acid on NAFLD was statistical significant (P < 0.05). CONCLUSIONS: MHO, MUNW, and MUO were associated with higher prevalence of NAFLD. Serum uric acid levels may modify the association between metabolically phenotypes and NAFLD.


Assuntos
Hiperuricemia , Síndrome Metabólica , Hepatopatia Gordurosa não Alcoólica , Obesidade Metabolicamente Benigna , Humanos , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Sobrepeso/complicações , Ácido Úrico , Obesidade Metabolicamente Benigna/diagnóstico , Obesidade Metabolicamente Benigna/epidemiologia , Hiperuricemia/complicações , Hiperuricemia/epidemiologia , Obesidade , Fenótipo , Síndrome Metabólica/complicações , Índice de Massa Corporal , Fatores de Risco
3.
J Orthop Surg Res ; 18(1): 61, 2023 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-36683056

RESUMO

BACKGROUND: This study aimed to explore the clinical characteristics of perioperative acute gout attacks in patients with varying uric acid levels undergoing orthopedic surgery, identify the risk factors for gout recurrence within the first postoperative year, and provide a disease prevention and diagnostic reference. METHODS: This hospital-based retrospective study was conducted between January 2018 and December 2020. According to the blood uric acid levels at admission, the patients were grouped into either the normal uric acid level group or the hyperuricemia group. Patient comorbidities, serum uric acid levels, inflammatory indicators, follow-up recurrence rates, and other indicators were compared. RESULT: The uric acid decline ratio and the inflammatory indexes (white blood cell count and C-reactive protein level) at the time of the attack were significantly higher in the normal uric acid level group than in the hyperuricemia group (P < 0.05). Patients in the hyperuricemia group with diabetes and tophi and those administered diuretics were more prone to acute gout attacks than those in the normal uric acid level group (P < 0.05). In the normal uric acid level group, 22 patients (84.6%) exhibited single joint involvement, whereas only 18 patients (47.4%) in the hyperuricemia group demonstrated single joint involvement (P < 0.05). After 1 year of follow-up, the gout recurrence rate in the hyperuricemia group was 44.7%, which was significantly higher that the recurrence rate in the normoglycemic group (11.5%; P < 0.05). Presenting tophi in perioperative orthopedic surgery patients was found to be an independent risk factor for gout recurrence within 1 year (RR = 4.80; P = 0.029). CONCLUSION: The recurrence rate of gout in patients with hyperuricemia during perioperative period increased 1 year after operation. Therefore, it is crucial to monitor the uric acid level to prevent acute gout attacks during the perioperative period and recurrence during the 1-year follow-up period. Moreover, the risk of an acute gout recurrence 1 year after operation increased in patients who presented tophi; therefore, it is necessary to maintain appropriate blood uric acid level during perioperative period among patients undergoing orthopedic surgery.


Assuntos
Artrite Gotosa , Gota , Hiperuricemia , Procedimentos Ortopédicos , Humanos , Hiperuricemia/complicações , Hiperuricemia/diagnóstico , Ácido Úrico , Estudos Retrospectivos , Gota/cirurgia , Gota/diagnóstico , Fatores de Risco , Procedimentos Ortopédicos/efeitos adversos , Período Perioperatório
4.
J Agric Food Chem ; 71(3): 1620-1627, 2023 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-36625439

RESUMO

The xanthine oxidase (XO) inhibitory peptides from pacific white shrimp or swimming crab were identified by molecular docking, and the anti-hyperuricemic activity of the peptides was confirmed in hyperuricemic cells. In our study, 17 novel XO inhibitory peptides were purified from pacific white shrimp or swimming crab, and Ala-Glu-Ala-Gln-Met-Trp-Arg (AEAQMWR, 891.01 Da, IC50 = 8.85 ± 0.05 mM) exhibited the greatest XO inhibitory activity in vitro. Molecular docking results indicated that attractive charge, salt bridge, and hydrogen bond showed a crucial effect on the interactions of XO inhibitory peptides with the pivotal residues of Arg880, Glu802, and Glu1261. In addition, XO inhibitory peptides alleviated hyperuricemia by inhibiting inflammation and preventing increased uric acid transporter expression levels in hyperuricemia cells. Overall, these results further confirmed that screening of XO inhibitory peptides rapidly via molecular docking was feasible.


Assuntos
Braquiúros , Hiperuricemia , Animais , Simulação de Acoplamento Molecular , Xantina Oxidase/metabolismo , Inibidores Enzimáticos/química , Hiperuricemia/tratamento farmacológico , Hiperuricemia/metabolismo , Natação , Peptídeos
5.
Artigo em Inglês | MEDLINE | ID: mdl-36674173

RESUMO

The incidence of chronic kidney disease (CKD) is increasing worldwide; however, the association between CKD and anemia and hyperuricemia has yet to be clarified. In addition, whether anemia and hyperuricemia only influence renal damage in combination with other comorbidities or whether they are direct causative factors is also controversial. Therefore, the aim of this longitudinal study was to investigate these issues in a large Taiwanese cohort. We enrolled 26,631 participants from the Taiwan Biobank (TWB) after excluding those with CKD at the baseline, all of whom had follow-up data for a median of 4 years. In this study, CKD was defined as an estimated glomerular filtration rate < 60 mL/min/1.73 m2, incident new-onset CKD was defined as the development of CKD during follow-up, anemia was defined as a hemoglobin level <13 mg/dL in males and <12 mg/dL in females, and hyperuricemia was defined as a serum uric acid (UA) level >7 mg/dL in males and >6 mg/dL in females. The participants were divided into four groups according to whether or not they had anemia and hyperuricemia. Multivariable analysis showed that low hemoglobin (per 1 g/dL; odds ratio [OR], 0.760; p < 0.001) and high serum UA (per 1 mg/dL; OR, 1.444; p < 0.001) in model 1 and anemia (OR, 2.367; p < 0.001) and hyperuricemia (OR, 2.516; p < 0.001) in model 2 were significantly associated with new-onset CKD. Furthermore, compared to the group without anemia or hyperuricemia, the groups with anemia without hyperuricemia (OR, 2.502; p < 0.001), without anemia with hyperuricemia (OR, 2.559; p < 0.001), and with anemia and hyperuricemia (OR, 5.505; p < 0.001) were significantly associated with new-onset CKD. There was a significant interaction between hemoglobin and serum UA and new-onset CKD (p < 0.001). In conclusion, we found that anemia and hyperuricemia were associated with new-onset CKD, respectively, and also had a synergetic effect on new-onset CKD.


Assuntos
Anemia , Hiperuricemia , Insuficiência Renal Crônica , Masculino , Feminino , Humanos , Seguimentos , Estudos Longitudinais , Hiperuricemia/complicações , Hiperuricemia/epidemiologia , Ácido Úrico , Insuficiência Renal Crônica/epidemiologia , Insuficiência Renal Crônica/etiologia , Anemia/etiologia , Anemia/complicações , Taxa de Filtração Glomerular , Fatores de Risco
6.
PeerJ ; 11: e14554, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36632144

RESUMO

Background: Hyperuricemia and gout are a group of disorders of purine metabolism. In recent years, the incidence of hyperuricemia and gout has been increasing, which is a severe threat to people's health. Several studies on hyperuricemia and gout in proteomics and metabolomics have been conducted recently. Some literature has identified biomarkers that distinguish asymptomatic hyperuricemia from acute gout or remission of gout. We summarize the physiological processes in which these biomarkers may be involved and their role in disease progression. Methodology: We used professional databases including PubMed, Web of Science to conduct the literature review. This review addresses the current landscape of hyperuricemia and gout biomarkers with a focus on proteomics and metabolomics. Results: Proteomic methods are used to identify differentially expressed proteins to find specific biomarkers. These findings may be suggestive for the diagnosis and treatment of hyperuricemia and gout to explore the disease pathogenesis. The identified biomarkers may be mediators of the link between hyperuricemia, gout and kidney disease, metabolic syndrome, diabetes and hypertriglyceridemia. Metabolomics reveals the main influential pathways through small molecule metabolites, such as amino acid metabolism, lipid metabolism, or other characteristic metabolic pathways. These studies have contributed to the discovery of Chinese medicine. Some traditional Chinese medicine compounds can improve the metabolic disorders of the disease. Conclusions: We suggest some possible relationships of potential biomarkers with inflammatory episodes, complement activation, and metabolic pathways. These biomarkers are able to distinguish between different stages of disease development. However, there are relatively few proteomic as well as metabolomic studies on hyperuricemia and gout, and some experiments are only primary screening tests, which need further in-depth study.


Assuntos
Gota , Hiperuricemia , Humanos , Hiperuricemia/diagnóstico , Proteômica , Gota/diagnóstico , Ácido Úrico , Biomarcadores
7.
J Enzyme Inhib Med Chem ; 38(1): 2163241, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36629443

RESUMO

In this work, a series of novel compounds Spartinin C1-C24 were screened, synthesised and evaluated for inhibiting xanthine oxidase thus lowering serum uric acid level. The backbones were derived from the components of coastal marine source Spartina alterniflora and marketed drugs. The top hits Spartinin C10 & C22 suggested high inhibition percentages (78.54 and 93.74) at 10 µM dosage, which were higher than the positive control Allopurinol. They were low cytotoxic onto human normal hepatocyte cells. Treatment with Spartinin C10 could lower the serum uric acid level to 440.0 µM in the hyperuricemic model mice (723.0 µM), comparable with Allopurinol (325.8 µM). Spartinin C10 was more appreciated than Allopurinol on other serum indexes. The preliminary pharmacokinetics evaluation indicated that the rapid absorption, metabolism and elimination of Spartinin C10 should be further improved. The discovery of pharmaceutical molecules from coastal marine source here might inspire the inter-disciplinary investigations on public health.


Assuntos
Alopurinol , Hiperuricemia , Humanos , Camundongos , Animais , Alopurinol/farmacologia , Alopurinol/uso terapêutico , Ácido Úrico/uso terapêutico , Ácidos Cumáricos , Hiperuricemia/tratamento farmacológico , Xantina Oxidase/metabolismo
8.
Sci Rep ; 13(1): 93, 2023 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-36639673

RESUMO

Two-thirds of urate is excreted via the renal pathway and the remaining one-third via the extra-renal pathway, the latter mainly via the intestine in healthy individuals. ABCG2, a urate exporter, is expressed in various tissues including the kidney and intestine, and its dysfunction leads to hyperuricemia and gout. ABCG2 is regarded as being responsible for most of the extra-renal urate excretion. However, the extra-renal urate excretion capacity via ABCG2 remains undefined in end-stage kidney diseases. Therefore, we evaluated the capacity of extra-renal ABCG2 using 123 anuric hemodialysis patients whose urate excretion depended on only the extra-renal pathway. ABCG2 function in each participant was estimated based on ABCG2 dysfunctional variants. We computed the uric acid pool (PoolUA) from bodyweight and serum urate level (SUA) using previously reported radio-isotopic data, and we analyzed the association between ABCG2 function and the PoolUA. SUA and PoolUA increased significantly with ABCG2 dysfunction, and extra-renal ABCG2 could excrete up to approximately 60% of the daily uric acid turnover in hemodialysis patients. Our findings indicate that the extra-renal urate excretion capacity can expand with renal function decline and highlight that the extra-renal pathway is particularly important in the uric acid homeostasis for patients with renal dysfunction.


Assuntos
Gota , Hiperuricemia , Humanos , Ácido Úrico , Rim/metabolismo , Gota/genética , Gota/metabolismo , Diálise Renal , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/genética , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/metabolismo , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo
9.
Chempluschem ; 88(1): e202200286, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36591998

RESUMO

Nanozymes have advantages over natural enzymes in terms of efficiency, stability, and economy. MVSM (Mixed Valence State MOF) is a nano-oxidase with uricase-like activity that may catalyze uric acid (UA) in the body into allantoin and H2 O2 to treat gout and hyperuricemia by substituting natural uricase. However, it cannot specifically identify and choose UA. To increase the selectivity and affinity of MVSM for UA, the composite material MVSM@MIP is innovatively synthesized using a new synthetic approach termed the "two-step synthesis method," which may prevent UA from being oxidized by MVSM during manufacture in this study. At the same time, this study also provides experimental proof of the effective creation of the material, the advantages of the "two-step synthesis approach," and the high selectivity and affinity of MVSM@MIP for UA. Based on these findings, the suggested technique may be used to effectively catalyze uric acid in human urine with high activity.


Assuntos
Hiperuricemia , Ácido Úrico , Humanos , Ácido Úrico/urina , Polímeros Molecularmente Impressos , Urato Oxidase
10.
J Agric Food Chem ; 71(3): 1434-1446, 2023 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-36525382

RESUMO

Hyperuricemia characterized by high serum levels of uric acid (UA, >6.8 mg/dL) is regarded as a common chronic metabolic disease. When used as a food supplement, naringenin might have various pharmacological activities, including antioxidant, free-radical-scavenging, and inflammation-suppressing activities. However, the effects of naringenin on hyperuricemia and renal inflammation and the underlying mechanisms remain to be elucidated. Here, we comprehensively examined the effects of naringenin on hyperuricemia and the attenuation of renal impairment. Mice were injected with 250 mg/kg of potassium oxonate (PO) and given 5% fructose water to induce hyperuricemia. The pharmacological effects of naringenin (10 and 50 mg/kg) and benzbromarone (positive control group, 20 mg/kg) on hyperuricemic mice were evaluated in vivo. The disordered expression of urate transporters in HK-2 cells was stimulated by 8 mg/dL UA, which was used to determine the mechanisms underlying the effects of naringenin in vitro. Naringenin markedly reduced the serum UA level in a dose-dependent manner and improved renal dysfunction. Moreover, the increased elimination of UA in urine showed that the effects of naringenin were associated with the regulation of renal excretion. Further examination indicated that naringenin reduced the expression of GLUT9 by inhibiting the PI3K/AKT signaling pathway and reinforced the expression of ABCG2 by increasing the abundance of PDZK1 in vivo and in vitro. Furthermore, sirius red staining and western blotting indicated that naringenin plays a protective role in renal injury by suppressing increases in the levels of pro-inflammatory cytokines, including IL-6 and TNF-α, which contribute to the inhibition of the TLR4/NF-κB signaling pathway in vivo and in vitro. Naringenin supplementation might be a potential therapeutic strategy to ameliorate hyperuricemia by promoting UA excretion in the kidney and attenuating the inflammatory response by decreasing the release of inflammatory cytokines. This study shows that naringenin could be used as a functional food or dietary supplement for hyperuricemia prevention and treatment.


Assuntos
Hiperuricemia , Camundongos , Animais , Hiperuricemia/metabolismo , NF-kappa B/genética , NF-kappa B/metabolismo , Ácido Úrico/metabolismo , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Eliminação Renal , Rim/metabolismo , Transdução de Sinais , Inflamação/tratamento farmacológico , Inflamação/genética , Inflamação/metabolismo , Citocinas/metabolismo , Ácido Oxônico
11.
J Agric Food Chem ; 71(1): 320-330, 2023 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-36530149

RESUMO

The metabolic disease hyperuricemia (HUA) is characterized by a disturbance in purine metabolism. Peptides, such as marine fish-derived peptides, have previously been shown to be effective in alleviating HUA. In this study, HUA rats were induced by potassium oxonate with 100 mg/kg (L), 200 mg/kg (M), and 400 mg/kg (H) of marine fish protein peptide (MFPP). The results showed that MFPP could effectively reduce the serum uric acid (SUA) levels compared with the model group rats; kidney histopathology and the levels of inflammatory factors (TNF-α, IL-6, and IL-10) indicated that MFPP attenuated HUA-induced kidney inflammation. Meanwhile, MFPP restored the abundance of beneficial bacteria, including Lactobacillus, Blautia, Colidextribacter, and Intestinimonas. MFPP further repaired the intestinal barrier by recovering the expression of gene Ildr2 encoding the tricellular tight junction protein ILDR2 and the immune-related genes Ccr7 and Nr4a3 and also regulated the expression of Entpd8 and Cyp27b1 to restore kidney function and uric acid metabolism. MFPP was proved to have potential as a therapeutic strategy to be included in dietary intervention to relieve HUA.


Assuntos
Hiperuricemia , Enteropatias , Ratos , Animais , Hiperuricemia/induzido quimicamente , Hiperuricemia/tratamento farmacológico , Hiperuricemia/genética , Ácido Úrico/metabolismo , Proteínas de Peixes/metabolismo , Rim/metabolismo , Enteropatias/metabolismo , Proteínas de Transporte/metabolismo , Inflamação/tratamento farmacológico , Inflamação/genética , Inflamação/metabolismo , Peptídeos/metabolismo
12.
Ecotoxicol Environ Saf ; 249: 114354, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36508833

RESUMO

BACKGROUND AND OBJECTIVES: Studies on the effects of airborne particulates of diameter ≤ 1 µm (PM1), airborne particulates of diameter ≤ 2.5 µm (PM2.5) and airborne particulates of diameter ranges from 1 to 2.5 µm (PM1-2.5) on incidence of hyperuricemia are limited. We aimed to investigate the associations between PM1, PM2.5, and PM1-2.5 and hyperuricemia among male traffic officers. METHODS: We conducted a prospective cohort study of 1460 traffic officers without hyperuricemia in Guangzhou, China from 2009 to 2016. Exposures of PM1 and PM2.5 were estimated with a spatiotemporal model. PM1-2.5 concentrations were calculated by subtracting PM1 from PM2.5 concentrations. Cox's proportional hazards regressions models were used to examine the association between PM1, PM2.5, and PM1-2.5 and hyperuricemia, adjusted for potential confounders. Associations between PM1, PM2.5, and PM1-2.5 and serum uric acid (SUA) levels were evaluated with multiple linear regression models. RESULTS: Hazard ratios (HRs) and 95% confidence intervals (CIs) of hyperuricemia associated with 10 µg/m3 increment in PM1, PM2.5, and PM1-2.5 were 1.67 (95% CI:1.30-2.36), 1.49 (95% CI: 1.27-1.75), and 2.18 (95% CI: 1.58-3.02), respectively. The SUA concentrations increased by 12.23 µmol/L (95% CI: 5.91-18.56), 6.93 µmol/L (95% CI: 3.02-10.84), and 8.72 µmol/L (95% CI: 0.76-16.68) per 10 µg/m3 increase in PM1, PM2.5, and PM1-2.5, respectively. Stratified analyses indicated the positive associations of PM2.5 and PM1-2.5 with SUA levels were stronger in non-smokers, and PM1, PM2.5, and PM1-2.5 with SUA levels were stronger in non-drinkers. CONCLUSION: Long-term PM1, PM2.5, and PM1-2.5 exposures may increase the risk of hyperuricemia and elevate SUA levels among male traffic officers, especially in non-smokers and non-drinkers.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Hiperuricemia , Humanos , Masculino , Material Particulado/toxicidade , Material Particulado/análise , Poluentes Atmosféricos/análise , Hiperuricemia/epidemiologia , Estudos Prospectivos , Ácido Úrico/análise , Exposição Ambiental/efeitos adversos , Exposição Ambiental/análise , China/epidemiologia , Poluição do Ar/análise
13.
Int Immunopharmacol ; 114: 109568, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36527883

RESUMO

Cancer is a disease caused when cells divide uncontrollably and spread into surrounding tissues. There are different therapeutic modalities that control cancer growth, of which surgery, chemotherapy, and radiotherapy. Chemotherapy is a cancer treatment approach in which medications are used to inhibit cell proliferation and tumor multiplication, thus avoiding invasion and metastasis and thus eradicate cancer. One of the common complications associated with cancer chemotherapy is rapid lysis of expanding tumor cells, known as tumor lysis syndrome (TLS). TLS is associated with number of metabolic changes such as hyperuricemia, hyperkalemia, hyperphosphatemia and hypocalcemia. Among the consequences of hyperuricemia, hyperkalemia, hyperphosphatemia and hypocalcemia is the inhibition of 5' AMP-activated protein kinase (AMPK). Inhibition of AMPK induced different cancer chemo-resistance mechanisms such as cancer stem cells (CSCs), p-glycoproteins, Octamer-binding transcription factor 4 (OCT-4), homeobox protein NANOG, Krüppel-like factor 4 (KLF4) and immune microenvironment and thus leads to poor response to chemotherapy and even relapses after treatment. Our review aims to uncover new mechanisms underlying the metabolic consequences of tumor lysis on AMPK in tumor microenvironment. In this review, we also investigated the effect of AMPK on different cancer chemo-resistance mechanisms such as cancer stem cells, p-glycoproteins, OCT-4, NANOG, KLF4 and immune microenvironment.


Assuntos
Hiperpotassemia , Hiperfosfatemia , Hiperuricemia , Hipocalcemia , Síndrome de Lise Tumoral , Humanos , Proteínas Quinases Ativadas por AMP , Resistencia a Medicamentos Antineoplásicos , Hiperpotassemia/complicações , Hiperpotassemia/terapia , Hiperfosfatemia/complicações , Hipocalcemia/complicações , Hipocalcemia/terapia , Recidiva Local de Neoplasia , Síndrome de Lise Tumoral/etiologia , Síndrome de Lise Tumoral/terapia , Microambiente Tumoral , Inibidores de Proteínas Quinases/uso terapêutico
14.
Bioorg Chem ; 131: 106320, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36527991

RESUMO

Xanthine oxidase (XO) is a crucial target for the treatment of hyperuricemia and gout. A series of derivatives based on natural 3,4-dihydroxychalcone, obtained from Carthamus tinctorious and Licorice, were designed and synthesized. Nine derivatives (9a-e, 10b,c, and 15a,b) exhibited apparent XO inhibitory activity in vitro (IC50 values varied from 0.121 to 7.086 µM), 15b presented the most potent inhibitory activity (IC50 = 0.121 µM), which was 27.47-fold higher than that of allopurinol (IC50 = 3.324 µM). The SAR analysis indicated that introducing hydroxyl groups at 3'/4'/5'-position on ring A was more beneficial to the inhibition of XO than at 2'/6'-position; the removal of 3­hydroxyl group on ring B could weaken the inhibitory potency of hydroxychalcones on XO, but it was beneficial to the XO inhibitory potency of methoxychalcones. Molecule modeling studies afforded insights into the binding mode of 15b with XO and supported the findings of SAR analysis. Additionally, kinetics studies demonstrated that 15b presented a reversible and competitive XO inhibitor, which spontaneously combined with XO through hydrophobic force, and finally changed the secondary conformation of XO. Furthermore, the acute hyperuricemia model was employed to investigate the hypouricemic effect of 15b, which could effectively reduce the serum uric acid levels of rats at an oral dose of 10 mg/kg. ADMET prediction suggested that compound 15b possessed good pharmacokinetic properties. Briefly, compound 15b emerges as an interesting XO inhibitor for the treatment of hyperuricemia and gout with beneficial effects on serum uric acid levels regulating. Meanwhile, the XO inhibitors with chalcone skeleton will deserve further attention and discussion.


Assuntos
Chalcona , Chalconas , Gota , Hiperuricemia , Ratos , Animais , Relação Estrutura-Atividade , Ácido Úrico , Chalconas/farmacologia , Chalconas/uso terapêutico , Xantina Oxidase , Chalcona/farmacologia , Chalcona/uso terapêutico , Hiperuricemia/tratamento farmacológico , Hiperuricemia/metabolismo , Inibidores Enzimáticos/química , Gota/tratamento farmacológico
15.
J Clin Hypertens (Greenwich) ; 25(1): 78-85, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36573350

RESUMO

Previous studies focused on the relationships between Serum Uric Acid (SUA) and lipids have found an association mainly with triglycerides. Furthermore, previous studies on adiposity indices have been focused on the evaluation of the Visceral Adiposity Index (VAI). The present study was aimed at providing within the same population a systematic evaluation of lipids and adiposity indices with SUA, employing both the classic cutoff for hyperuricemia and the newly one identified by the Uric Acid Right for Heart Health (URRAH) study. We analyzed data collected in 1892 subjects of the Pressioni Arteriose Monitorate E loro Associazioni (PAMELA) study with available SUA, lipid profile and variables necessary to calculate VAI, Cardio-Metabolic Index (CMI) and Lipid Accumulation Product (LAP). At linear regression model (corrected for confounders) SUA correlated with all the lipids values (with the strongest ß for triglycerides) and adiposity indices. When the two different cutoffs were compared, the URRAH one was significantly related to atherogenic lipids profile (OR 1.207 for LDL and 1.33 for non-HDL, P < 0.001) while this was not the case for the classic one. Regarding adiposity indices the classic cutoff displays highest OR as compared to the URRAH one. In conclusions, newly reported URRAH cutoff for hyperuricemia better relate to atherogenic lipoprotein (LDL and non-HDL) when compared to the classic one. The opposite has been found for adiposity indexes where the classic cut-off seems to present highest performance. Among adiposity indexes, LAP present the highest OR for the relationship with hyperuricemia.


Assuntos
Hipertensão , Hiperuricemia , Humanos , Adiposidade , Ácido Úrico , Hiperuricemia/complicações , Hipertensão/complicações , Obesidade/complicações , Triglicerídeos , Obesidade Abdominal/epidemiologia , Índice de Massa Corporal
16.
J Agric Food Chem ; 71(1): 382-397, 2023 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-36562602

RESUMO

Hyperuricemic nephropathy (HN) is caused by urate crystals that get deposited in the kidney and contribute to renal fibrosis. Uric acid (UA) has been proven to directly cause renal mesangial cell oxidative stress and fibrosis in the pathogenesis of HN. Some antioxidants can be used as chemopreventive agents of HN. Hibiscus sabdariffa leaf extracts (HLE), rich in polyphenol, have been shown to possess hypoglycemic, antioxidant, hypolipidemic, antiatherosclerotic, and anticancer effects. The aim of the study is to examine the inhibitory effect of HLE and its main component ellagic acid (EA) on renal fibrosis. In vitro, mouse renal glomerular mesangial SV40MES13 cells pretreated with UA were demonstrated to trigger obvious morphological changes and viability loss, as well as affect matrix metalloproteinases (MMPs) activities. Noncytotoxic doses of HLE and EA abolished the UA-induced cell injury and MMP-2/9 secretion. In addition, HLE and EA exhibited antioxidant and anti-inflammatory effects on the UA-treated cells with a reduction in transforming growth factor-beta (TGF-ß) production. Next, the UA-activated pro-fibrotic factors, extracellular matrix (ECM) deposition, and epithelial-mesenchymal-transition (EMT) were inhibited by HLE or EA. Mechanistic assays indicated that antifibrotic effects of HLE might be mediated via TGF-ß/Smad signaling, as confirmed by the transfection of Smad7 siRNA. In vivo, HLE and EA supplementations significantly alleviated HN development, which may result from inhibiting adenine-induced TGF-ß production accompanying oxidative stress and inflammation, as well as fibrogenesis. Our data imply that EA-enriched HLE regulates the TGF-ß/Smad signaling, which in turn led to reduced renal mesangial cell injury and fibrosis in HN and provided a new mechanism for its nephroprotective activity.


Assuntos
Hibiscus , Hiperuricemia , Nefropatias , Animais , Camundongos , Antioxidantes/uso terapêutico , Ácido Elágico/farmacologia , Fibrose , Hibiscus/química , Hiperuricemia/tratamento farmacológico , Hiperuricemia/genética , Nefropatias/tratamento farmacológico , Nefropatias/genética , Nefropatias/prevenção & controle , Fator de Crescimento Transformador beta , Ácido Úrico , Folhas de Planta/química
17.
Environ Pollut ; 318: 120891, 2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-36529338

RESUMO

Ubiquitous polycyclic aromatic hydrocarbons (PAHs) and metals could induce hyperuricemia and oxidative damage individually, while their co-exposure effects on hyperuricemia risk and the potential roles of oxidative damage in these health outcomes remain poorly understood. We conducted a cross-sectional study in 1379 coke oven workers. We evaluated the levels of PAH-metal exposure and oxidative damage by urinary monohydroxy-PAHs, plasma benzo [a]pyrene-7,8-diol-9,10-epoxide-albumin (BPDE-Alb) adducts, urinary metals, urinary 8-iso-prostaglandin-F2α, and urinary 8-hydroxydeoxyguanosine (8-OH-dG). The subjects were classified into cases of hyperuricemia and controls by the levels of blood uric acid. We found that the sum of multiple hydroxyphenanthrene (ΣOH-Phe) was robustly associated with the increase in hyperuricemia risk, while rubidium and strontium had robust protective associations with hyperuricemia risk (Ptrend<0.05). The risk association of ΣOH-Phe was weaker in workers with high levels of rubidium and strontium [P for modifying effect (PME) < 0.030]. The protective association of strontium was more pronounced in workers with higher ΣOH-Phe (PME = 0.014). We also found that 8-OH-dG was a risk factor for hyperuricemia (Ptrend = 0.006) and mediated 10.13% of the elevated hyperuricemia risk associated with ΣOH-Phe. Our findings suggested that individual PAHs and metals, as well as their co-exposure, may influence hyperuricemia risk among coke oven workers, with oxidative DNA damage playing a potential mediating role in their associations.


Assuntos
Coque , Hiperuricemia , Exposição Ocupacional , Hidrocarbonetos Policíclicos Aromáticos , Humanos , Hidrocarbonetos Policíclicos Aromáticos/toxicidade , 8-Hidroxi-2'-Desoxiguanosina , Exposição Ocupacional/efeitos adversos , Exposição Ocupacional/análise , Rubídio , Estudos Transversais , Hiperuricemia/induzido quimicamente , Hiperuricemia/epidemiologia , Metais , Estrôncio , Estresse Oxidativo , Dano ao DNA
18.
Medicine (Baltimore) ; 101(47): e32094, 2022 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-36451481

RESUMO

Prospective evidence on the association of obesity and metabolic health status and its transition over time with the risk of hyperuricemia in the Chinese population is limited. This study aims to investigate the phenotypic transition characteristics of metabolic obesity in Chinese adults and its association with hyperuricemia. Using the China Health and Retirement Longitudinal Survey (CHARLS) survey data in 2011 and 2015, 6059 adults aged ≥ 18 years were selected as the research people. The participants' general information, living habits, blood sample testing, and blood uric acid testing data during follow-up were extracted. According to body weight and metabolic health status, obesity phenotypes were divided into: metabolically normal weight group (MHNW), metabolically normal overweight/obesity group (MHOWO); metabolically abnormal normal weight group (MUNW); metabolically abnormal overweight/obese group (MUHOWO). Multiple linear regression was used to evaluate the correlation between metabolic obesity phenotype and serum uric acid level, and logistic regression model was used to analyze the association of metabolic obesity phenotype and transition with the risk of hyperuricemia. The average age of all subjects was (58.62 ±â€…8.93) years old, and 42.1% were male. The MHOWO phenotype was present in 19.2% of the general population and 48.6% of the baseline who were overweight or obese population. During the 4-year follow-up period, only 10.7% of participants with MHNW at baseline converted to MHOWO. Among MHOWO participants, 21.2% converted to MUHOWO. MHOWO also increased the risk of hyperuricemia (OR, 1.57; 95% CI 1.15-2.13; P = .004), both in obese and normal-weight individuals, even when metabolic status changed from unhealthy to healthy. Risk of hyperuricemia was high among those who remained metabolically unhealthy but of normal weight (OR, 3.09; 95% CI 1.51-6.30; P = .001). MHOWO also increases the risk of hyperuricemia, and MHOWO remains stable or changes to MUHOWO, which increases the risk of hyperuricemia. Therefore, close attention should be paid to the transition of metabolic health status over time, and individualized prevention strategies should be focused on metabolically unhealthy and obese individuals.


Assuntos
Hiperuricemia , Humanos , Masculino , Feminino , Hiperuricemia/complicações , Hiperuricemia/epidemiologia , Estudos de Coortes , Sobrepeso/complicações , Sobrepeso/epidemiologia , Ácido Úrico , Estudos Prospectivos , Obesidade/complicações , Obesidade/epidemiologia , Fenótipo
19.
Int Immunopharmacol ; 113(Pt A): 109375, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36461592

RESUMO

BACKGROUND: Recent studies have uncovered that hyperuricemia (HUA) leads to cognitive deficits, which are accompanied by neuronal damage and neuroinflammation. Here, we aim to explore the role of methyltransferase-like 3 (METTL3) in HUA-mediated neuronal apoptosis and microglial inflammation. METHODS: A HUA mouse model was constructed. The spatial memory ability of the mice was assessed by the Morris water maze experiment (MWM), and neuronal apoptosis was analyzed by the TdT-mediated dUTP nick end labeling (TUNEL) assay. Besides, enzyme-linked immunosorbent assay (ELISA) was utilized to measure the contents of inflammatory factors (IL-1ß, IL-6, and TNF-α) and oxidative stress markers (MDA, SOD, and CAT) in the serum of mice. In vitro, the mouse hippocampal neuron (HT22) and microglia (BV2) were treated with uric acid (UA). Flow cytometry was applied to analyze HT22 and BV2 cell apoptosis, and ELISA was conducted to observe neuroinflammation and oxidative stress. In addition, the expression of MyD88, p-NF-κB, NF-κB, NLRP3, ASC and Caspase1 was determined by Western blot. RESULTS: METTL3 and miR-124-3p were down-regulated, while the MyD88-NF-κB pathway was activated in the HUA mouse model. UA treatment induced neuronal apoptosis in HT22 and stimulated microglial activation in BV2. Overexpressing METTL3 alleviated HT22 neuronal apoptosis and resisted the release of inflammatory cytokines and oxidative stress mediators in BV2 cells. METTL3 repressed MyD88-NF-κB and NLRP3-ASC-Caspase1 inflammasome. In addition, METTL3 overexpression enhanced miR-124-3p expression, while METTL3 knockdown aggravated HT22 cell apoptosis and BV2 cell overactivation. CONCLUSION: METTL3 improves neuronal apoptosis and microglial activation in the HUA model by choking the MyD88/NF-κB pathway and up-regulating miR-124-3p.


Assuntos
Disfunção Cognitiva , Hiperuricemia , MicroRNAs , Camundongos , Animais , NF-kappa B , Inflamassomos , Hiperuricemia/tratamento farmacológico , Fator 88 de Diferenciação Mieloide , Proteína 3 que Contém Domínio de Pirina da Família NLR , Proteínas Adaptadoras de Transdução de Sinal , Disfunção Cognitiva/tratamento farmacológico , Ácido Úrico , MicroRNAs/genética , Metiltransferases
20.
Front Immunol ; 13: 995582, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36466813

RESUMO

Periodontitis is one of the most prevalent diseases in oral cavity, which could not merely lead to the destruction of supporting or surrounding tooth structures but also affect the whole-body health such as the digestive and nervous systems. Epidemiological investigations suggested that in some developed countries, more than 45% or even 50% population were suffering from periodontitis. However, the prevalence increases with age remarkably and it is investigated that a high prevalence (>50%) is affecting the elderly who is over 65 years old. There is an increasing interest in the direct and indirect relationships between periodontitis and hyperuricemia. Currently, hyperuricemia has become the second major metabolic disease in modern society and the prevalence of hyperuricemia among adult males and females was 21.7% and 14.4% respectively. As an inflammatory disease associated with various systemic diseases, periodontitis may have certain connections with hyperuricemia. Partial existing research announced that hyperuricemia could act as an inhibitory factor for periodontitis, while other scholars presented that a high uric acid (UA) level was more likely to aggravate inflammatory immune response and lead to more serious tissue destruction. This article provides a detailed and comprehensive overview of the relationship underlying hyperuricemia and periodontitis in the molecular mechanisms. Given the impact of hyperuricemia, this review could provide insight into its comorbidities.


Assuntos
Hiperuricemia , Periodontite , Adulto , Idoso , Feminino , Masculino , Humanos , Hiperuricemia/epidemiologia , Periodontite/epidemiologia
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