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1.
Endocrine ; 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38722490

RESUMO

PURPOSE: Considering the prevalence of type 2 diabetes (T2D), osteoporosis should be considered a serious complication. However, an effective tool for the assessment of low bone mass mineral density (BMD) in T2D patients is not currently available. Therefore, the aim of our study was to establish a simple-to-use risk assessment tool by exploring risk factors for low BMD in T2D patients. METHODS: This study included 436 patients with a low BMD and 381 patients with a normal BMD. Multiple logistic regression analysis was performed to evaluate risk factors for low BMD in T2D patients. A nomogram was then developed from these results. A receiver operating characteristic (ROC) curve, calibration plot, and goodness-of-fit test were used to validate the nomogram. The clinical utility of the nomogram was also assessed. RESULTS: Multivariate logistic regression indicated that age, sex, education, body mass index (BMI), fasting C-peptide, high-density cholesterol (HDL), alkaline phosphatase (ALP), estimated glomerular filtration rate (eGFR), and type I collagen carboxy terminal peptide (S-CTX) were independent predictors for low BMD in T2D patients. The nomogram was developed from these variables using both the unadjusted area under the curve (AUC) and the bootstrap-corrected AUC (0.828). Calibration plots and the goodness-of-fit test demonstrated that the nomogram was well calibrated. CONCLUSIONS: The nomogram-illustrated model can be used by clinicians to easily predict the risk of low BMD in T2D patients. Our study also revealed that common factors are independent predictors of low BMD risk. Our results provide a new strategy for the prediction, investigation, and facilitation of low BMD in T2D patients.

2.
Cell Biol Int ; 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38741282

RESUMO

Polycystic ovary syndrome (PCOS) is the primary cause of female infertility with a lack of universal therapeutic regimen. Although osthole exhibits numerous pharmacological activities in treating various diseases, its therapeutic effect on PCOS is undiscovered. The present study found that application of osthole improved the symptoms of PCOS mice through preventing ovarian granulosa cells (GCs) production of more estrogen and alleviating the liberation of pro-inflammatory cytokine interleukin (IL)-1ß, IL-6, and tumor necrosis factor alpha. Meanwhile, osthole enhanced ovarian antioxidant capacity and alleviated intracellular reactive oxygen species (ROS) accumulation with a concurrent attenuation for oxidative stress, while intervention of antioxidant enzymic activity and glutathione (GSH) synthesis neutralized the salvation of osthole on GCs secretory disorder and chronic inflammation. Further analysis revealed that osthole restored the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and forkhead box O 1 (Foxo1) whose repression antagonized the amelioration of osthole on the insufficiency of antioxidant capacity and accumulation of ROS. Moreover, Nrf2 served as an intermedium to mediate the regulation of osthole on Foxo1. Additionally, osthole restricted the phosphorylation of IκBα and nuclear factor kappa B (NF-κB) subunit p65 by DHEA and weakened the transcriptional activity of NF-κB, but this effectiveness was abrogated by the obstruction of Nrf2 and Foxo1, whereas adjunction of GSH renewed the redemptive effect of osthole on NF-κB whose activation caused an invalidation of osthole in rescuing the aberration of GCs secretory function and inflammation response. Collectively, osthole might relieve the symptoms of PCOS mice via Nrf2-Foxo1-GSH-NF-κB pathway.

4.
Kidney Int Rep ; 9(4): 1057-1066, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38765575

RESUMO

Introduction: Immunoglobulin A nephropathy (IgAN) has been reported to coexist with hepatitis B virus (HBV) infection. Despite the clinical significance of this association, there is a lack of comprehensive research investigating the impact of various common conditions following HBV infection and the potential influence of anti-HBV therapy on the progression of IgAN. Methods: We investigated 3 distinct states of HBV infection, including chronic HBV infection, resolved HBV infection, and the deposition of hepatitis B antigens in renal tissue, in a follow-up database of 1961 patients with IgAN. IgAN progression was defined as a loss of estimated glomerular filtration rate (eGFR) >40%. Multivariable cause-specific hazards models to analyze the relationship between HBV states and IgAN progression. Results: Chronic HBV infection was identified as an independent risk factor for IgAN progression, supported by both prematching analysis (hazard ratio [HR], 1.61; 95% confidence interval [CI], 1.06-2.44; P = 0.024) and propensity-score matching analysis (HR, 1.74; 95% CI 1.28-2.37; P < 0.001). Conversely, resolved HBV infection showed no significant association with IgAN progression (HR, 1.01; 95% CI 0.67-1.52; P = 0.969). Moreover, the presence of HBV deposition in the kidneys and the utilization of anti-HBV therapy did not appear to be significant risk factors for renal outcomes (P > 0.05). Conclusion: Chronic HBV infection is an independent risk factor for IgAN progression, whereas resolved HBV infection is not. In patients with IgAN, management of concurrent chronic HBV infection should be enhanced. The presence of HBV deposition in the kidneys and the use of anti-HBV medications do not impact the kidney disease progression in patients with IgAN with concurrent HBV infection.

5.
J Int Med Res ; 52(5): 3000605241252607, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38749909

RESUMO

Rapid reduction of plasma triglycerides (TG) is believed to improve the outcome of pancreatitis in the context of hypertriglyceridaemia (HTG)-induced acute pancreatitis (HTG-AP). Previous studies have suggested that haemoperfusion (HP) with the Jafron cartridge series could be effective for reducing TG concentrations in patients with HTG-AP. However, the clearance capacity (CC) for TG removal has not been reported. This case series reports on data from three patients with HTG-AP who underwent HP with HA230 or HA330 cartridges. Blood samples were collected from both before and after the cartridge circuit every 30 min and the CC was calculated. Twelve pairs of blood samples were collected for each type of HP cartridge. The mean ± SD CC of the HA230 cartridge for TG removal in this case series was 0.009781 ± 1.117235 ml/min (95% confidence interval [CI], -0.7000762, 0.7196384 ml). The mean ± SD CC of the HA330 cartridge for TG removal in this case series was 0.344914 ± 1.412183 ml/min (95% CI, -0.5523448, 1.2421721 ml). Based on the findings of this small case series, special caution is advised when considering the use of the HA230 and HA330 cartridges for reducing blood TG concentration pending further conclusive evidence from larger studies.


Assuntos
Hemoperfusão , Hipertrigliceridemia , Pancreatite , Triglicerídeos , Humanos , Hipertrigliceridemia/sangue , Hipertrigliceridemia/complicações , Hipertrigliceridemia/terapia , Pancreatite/terapia , Pancreatite/sangue , Pancreatite/etiologia , Pancreatite/diagnóstico , Masculino , Hemoperfusão/métodos , Triglicerídeos/sangue , Pessoa de Meia-Idade , Feminino , Adulto , Doença Aguda , Idoso
6.
Nat Commun ; 15(1): 3721, 2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38698059

RESUMO

The enormous and widespread use of organoboronic acids has prompted the development of innovative synthetic methodologies to meet the demands on structural diversity and functional group tolerance. The existing photoinduced defunctionalization radical borylation, typically focused on the conversion of one C-X bond (X= Br, I, or other leaving group) into only one C-B bond. Herein, we disclose a divergent radical dechloroborylation reaction enabled by dinuclear gold catalysis with visible light irradiation. A wide range of structurally diverse alkyl boronic, α-chloroboronic, and gem-diboronic esters can be synthesized in moderate to good yields (up to 92%). Its synthetic robustness is further demonstrated on a preparative scale and applied to late-stage diversification of complex molecules. The process hinges on a C-Cl bond relay activation in readily available gem-dichloroalkanes through inner-sphere electron transfer, overcoming the redox potential limits of unreactive alkyl chlorides.

7.
J Cancer Res Clin Oncol ; 150(5): 258, 2024 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-38753091

RESUMO

PURPOSE: Breast cancer (BC) is the most prevalent malignant tumor worldwide among women, with the highest incidence rate. The mechanisms underlying nucleotide metabolism on biological functions in BC remain incompletely elucidated. MATERIALS AND METHODS: We harnessed differentially expressed nucleotide metabolism-related genes from The Cancer Genome Atlas-BRCA, constructing a prognostic risk model through univariate Cox regression and LASSO regression analyses. A validation set and the GSE7390 dataset were used to validate the risk model. Clinical relevance, survival and prognosis, immune infiltration, functional enrichment, and drug sensitivity analyses were conducted. RESULTS: Our findings identified four signature genes (DCTPP1, IFNG, SLC27A2, and MYH3) as nucleotide metabolism-related prognostic genes. Subsequently, patients were stratified into high- and low-risk groups, revealing the risk model's independence as a prognostic factor. Nomogram calibration underscored superior prediction accuracy. Gene Set Variation Analysis (GSVA) uncovered activated pathways in low-risk cohorts and mobilized pathways in high-risk cohorts. Distinctions in immune cells were noted between risk cohorts. Subsequent experiments validated that reducing SLC27A2 expression in BC cell lines or using the SLC27A2 inhibitor, Lipofermata, effectively inhibited tumor growth. CONCLUSIONS: We pinpointed four nucleotide metabolism-related prognostic genes, demonstrating promising accuracy as a risk prediction tool for patients with BC. SLC27A2 appears to be a potential therapeutic target for BC among these genes.


Assuntos
Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Prognóstico , Medição de Risco/métodos , Nucleotídeos/genética , Nomogramas , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Animais , Regulação Neoplásica da Expressão Gênica , Camundongos , Linhagem Celular Tumoral
8.
Int J Biol Macromol ; : 132371, 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38750861

RESUMO

Aflatoxin B1 (AFB1) is one of the most widespread contaminants in agricultural commodities. Pleurotus eryngii (PE) is widely used as a feed additive for its anti-inflammatory properties, and its major active substance is believed to be polysaccharides. This study aims to explore the underlying mechanism of dietary PE polysaccharides alleviating AFB1-induced toxicity in ducks. The major monosaccharide components of PE polysaccharides were identified as glucose, mannose, galactose, glucuronic acid, and fucose. The results showed that dietary PE polysaccharides could alleviate liver inflammation, alleviate intestinal barrier dysfunction, and change the imbalanced gut microbiota induced by AFB1 in ducks. However, PE polysaccharides failed to exert protective roles on the liver and intestine injury induced by AFB1 in antibiotic-treated ducks. The PE + AFB1-originated microbiota showed a positive effect on intestinal barrier and inflammation, the SCFAs transport via the gut-liver axis, and liver inflammation compared with the AFB1-originated microbiota in ducks. These findings provided a possible mechanism that PE polysaccharides alleviated AFB1-induced liver inflammation in ducks by remodeling gut microbiota, regulating microbiota-derived SCFAs transport via the gut-liver axis, and inhibiting inflammatory gene expressions in the liver, which may provide new insight for therapeutic methods against AFB1 exposure in animals.

9.
Angew Chem Int Ed Engl ; : e202406478, 2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38637953

RESUMO

A highly efficient and chemoselective approach for the divergent assembling of unsymmetrical hydrazines through an unprecedented intermolecular desulfurdioxidative N-N coupling is developed. This metal free protocol employs readily accessible N-arylhydroxylamines and N-sulfinylanilines to provide highly valuable hydrazine products with good yields and excellent functional group tolerance under simple conditions. Computational studies suggest that the in situ generated O-sulfenylated arylhydroxylamine intermediate undergoes a retro-[2π+2σ] cycloaddition via a stepwise diradical mechanism to form the N-N bond and release SO2.

10.
World J Diabetes ; 15(3): 488-501, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38591087

RESUMO

BACKGROUND: Diabetic kidney disease (DKD) is a major complication of diabetes mellitus. Renal tubular epithelial cell (TEC) damage, which is strongly associated with the inflammatory response and mesenchymal trans-differentiation, plays a significant role in DKD; However, the precise molecular mechanism is unknown. The recently identified microRNA-630 (miR-630) has been hypothesized to be closely associated with cell migration, apoptosis, and autophagy. However, the association between miR-630 and DKD and the underlying mechanism remain unknown. AIM: To investigate how miR-630 affects TEC injury and the inflammatory response in DKD rats. METHODS: Streptozotocin was administered to six-week-old male rats to create a hyperglycemic diabetic model. In the second week of modeling, the rats were divided into control, DKD, negative control of lentivirus, and miR-630 overexpression groups. After 8 wk, urine and blood samples were collected for the kidney injury assays, and renal tissues were removed for further molecular assays. The target gene for miR-630 was predicted using bioinformatics, and the association between miR-630 and toll-like receptor 4 (TLR4) was confirmed using in vitro investigations and double luciferase reporter gene assays. Overexpression of miR-630 in DKD rats led to changes in body weight, renal weight index, basic blood parameters and histopathological changes. RESULTS: The expression level of miR-630 was reduced in the kidney tissue of rats with DKD (P < 0.05). The miR-630 and TLR4 expressions in rat renal TECs (NRK-52E) were measured using quantitative reverse transcription polymerase chain reaction. The mRNA expression level of miR-630 was significantly lower in the high-glucose (HG) and HG + mimic negative control (NC) groups than in the normal glucose (NG) group (P < 0.05). In contrast, the mRNA expression level of TLR4 was significantly higher in these groups (P < 0.05). However, miR-630 mRNA expression increased and TLR4 mRNA expression significantly decreased in the HG + miR-630 mimic group than in the HG + mimic NC group (P < 0.05). Furthermore, the levels of tumor necrosis factor-alpha (TNF-α), interleukin-1ß (IL-1ß), and IL-6 were significantly higher in the HG and HG + mimic NC groups than in NG group (P < 0.05). However, the levels of these cytokines were significantly lower in the HG + miR-630 mimic group than in the HG + mimic NC group (P < 0.05). Notably, changes in protein expression were observed. The HG and HG + mimic NC groups showed a significant decrease in E-cadherin protein expression, whereas TLR4, α-smooth muscle actin (SMA), and collagen IV protein expression increased (P < 0.05). Conversely, the HG + miR-630 mimic group exhibited a significant increase in E-cadherin protein expression and a notable decrease in TLR4, α-SMA, and collagen IV protein expression than in the HG + mimic NC group (P < 0.05). The miR-630 targets TLR4 gene expression. In vivo experiments demonstrated that DKD rats treated with miR-630 agomir exhibited significantly higher miR-630 mRNA expression than DKD rats injected with agomir NC. Additionally, rats treated with miR-630 agomir showed significant reductions in urinary albumin, blood glucose, TLR4, and proinflammatory markers (TNF-α, IL-1ß, and IL-6) expression levels (P < 0.05). Moreover, these rats exhibited fewer kidney lesions and reduced infiltration of inflammatory cells. CONCLUSION: MiR-630 may inhibit the inflammatory reaction of DKD by targeting TLR4, and has a protective effect on DKD.

11.
Plants (Basel) ; 13(7)2024 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-38611502

RESUMO

In recent years, overuse of chemical fertilization has led to soil acidification and decreased rice yield productivity in southern China. Biochar and manure co-application remediation may have positive effects on rice yield and improve acid paddy soil fertility. This study was conducted to understand the effects of co-application of wood biochar and pig manure on rice yield and acid paddy soil quality (0-40 cm soil layers) in a 5-year field experiment. The experiment consisted of six treatments: no biochar and no fertilizer (CK); biochar only (BC); mineral fertilizer (N); mineral fertilizer combined with biochar (N + BC); manure (25% manure N replacing fertilizer N) combined with mineral fertilizer (MN); and manure combined with mineral fertilizer and biochar (MN + BC). Total nitrogen application for each treatment was the same at 270 kg nitrogen ha-1y-1, and 30 t ha-1 biochar was added to the soil only in the first year. After five years, compared with N treatments, N + BC, MN, and MN + BC treatments increased the rice yield rate to 2.8%, 4.3%, and 6.3%, respectively, by improving soil organic matter, total nitrogen, and available phosphate under a 0-40 cm soil layer. MN + BC had the strongest resistance to soil acidification among all the treatments. The interaction between fertilizers and biochar application was significant (p < 0.05) in rice yield, soil electrical conductivity (10-20 cm), and soil available phosphate (20-40 cm). Principal component analysis indicated that the effect of manure on soil property was stronger than that of biochar in the 0-40 cm soil layer. The overall rice yield and soil fertility decreased in the order of biochar + mineral fertilizer + manure > mineral fertilizer + manure > biochar + mineral fertilizer > mineral fertilizer > biochar > control. These results suggest that biochar and manure co-application is a long-term viable strategy for improving acid soil productivity due to its improvements in soil pH, organic carbon, nutrient retention, and availability.

12.
Ying Yong Sheng Tai Xue Bao ; 35(3): 817-826, 2024 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-38646770

RESUMO

To explore the causes of red tides in Qinhuangdao coastal water, we conducted surveys on both water quality and red tides during April to September of 2022 and analyzed the relationships between main environmental factors and red tide organisms through the factor analysis and canonical correspondence analysis. The results showed that there were eight red tides along the coast of Qinhuangdao in 2022, with a cumulative blooming area of 716.1 km2. The red tides could be divided into three kinds based on the major blooming organisms and occurrence time, Noctiluca scintillans bloom, diatom-euglena (Skeletonema costatum, Eutreptiella gymnastica, Pseudo-nitzschia spp.) bloom, and dinoflagellate (Scrippsiella trochoidea and Ceratium furca) bloom. Seasonal factor played roles mainly during July to September, while inorganic nutrients including nitrogen and phosphorus influenced the blooms mainly in April and July. The canonical correspondence analysis suggested that N. scintillans preferred low temperature, and often bloomed with high concentrations of ammonium nitrogen and dissolved inorganic phosphorus. S. costatum, E. gymnastica, and Pseudo-nitzschia spp. could tolerate broad ranges of various environmental factors, but favored high temperature and nitrogen-rich seawater. C. furca and S. trochoidea had higher survival rate and competitiveness in phosphate-poor waters. Combined the results from both analyses, we concluded that the causes for the three kinds of red tide processes in Qinhuangdao coastal areas in 2022 were different. Adequate diet algae and appropriate water temperature were important factors triggering and maintaining the N. scintillans bloom. Suitable temperature, salinity and eutrophication were the main reasons for the diatom-euglena bloom. The abundant nutrients and seawater disturbance promoted the germination of S. trochoidea cysts, while phosphorus limitation caused the blooming organism switched to C. furca and maintained the bloom hereafter.


Assuntos
Diatomáceas , Dinoflagellida , Monitoramento Ambiental , Proliferação Nociva de Algas , Água do Mar , China , Dinoflagellida/crescimento & desenvolvimento , Água do Mar/análise , Água do Mar/química , Diatomáceas/crescimento & desenvolvimento , Oceanos e Mares , Fósforo/análise , Nitrogênio/análise , Estações do Ano
13.
J Vet Pharmacol Ther ; 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38598665

RESUMO

Tilmicosin, a macrolide antibiotic, has the potential to treat bacterial infections in donkeys. However, the pharmacokinetics of tilmicosin in donkeys have not been reported. The aim of this study was to investigate the pharmacokinetics of tilmicosin in donkey plasma, urine, and feces after a single intragastric administration to determine the suitability of tilmicosin for donkeys. A total of 5 healthy male donkeys with similar body weights were selected. The donkeys were administered a single dose of 10 mg · kg-1 body weight (BW) tilmicosin by gavage. The concentrations of tilmicosin in plasma, urine, and feces were determined. The results showed that after a single intragastric administration of 10 mg · kg-1 body weight, tilmicosin in donkey plasma reached a maximum concentration of 11.23 ± 5.37 mg · L-1 at 0.80 ± 0.10 h, with a half-life of 14.49 ± 7.13 h, a mean residence time of 28.05 ± 3.05 h, a Cl/F of 0.48 ± 0.18 L · kg-1 · h-1, and a Vd/F of 9.28 ± 2.63 Lkg-1. The percentage of tilmicosin excreted through the urine of donkeys is 2.47%, and the percentage excreted through the feces is 66.43%. Our study provides data to inform the use of tilmicosin in donkeys.

14.
J Med Chem ; 67(9): 7088-7111, 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38634624

RESUMO

The novel metal(II)-based complexes HA-Cu, HA-Co, and HA-Ni with phenanthroline, sulfamethazine, and aromatic-aromatic coupled disulfamethazines as ligands were synthesized and characterized. HA-Cu, HA-Co, and HA-Ni all showed a broad spectrum of cytotoxicity and antiangiogenesis. HA-Cu was superior to HA-Co and HA-Ni, and even superior to DDP, showing significant inhibitory effect on the growth and development of tripe-negative breast cancer in vivo and in vitro. HA-Cu exhibited observable synergistic effects of antiproliferation, antiangiogenesis, anti-inflammatory, pro-apoptosis, and cuproptosis to effectively inhibited tumor survival and development. The molecular mechanism was confirmed that HA-Cu could downregulate the expression of key proteins in the VEGF/VEGFR2 signaling pathway and the expression of inflammatory cytokines, enhance the advantage of pro-apoptotic protein Bax, and enforce cuproptosis by weakening the expression of FDX1 and enhancing the expression of HSP70. Our research will provide a theoretical and practical reference for the development of metal-sulfamethazine and its derivatives as chemotherapy drugs for cancer treatment.


Assuntos
Inibidores da Angiogênese , Antineoplásicos , Apoptose , Complexos de Coordenação , Fenantrolinas , Neoplasias de Mama Triplo Negativas , Apoptose/efeitos dos fármacos , Humanos , Complexos de Coordenação/farmacologia , Complexos de Coordenação/química , Complexos de Coordenação/síntese química , Complexos de Coordenação/uso terapêutico , Animais , Fenantrolinas/farmacologia , Fenantrolinas/química , Fenantrolinas/síntese química , Feminino , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/patologia , Neoplasias de Mama Triplo Negativas/metabolismo , Inibidores da Angiogênese/farmacologia , Inibidores da Angiogênese/síntese química , Inibidores da Angiogênese/química , Inibidores da Angiogênese/uso terapêutico , Antineoplásicos/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Proliferação de Células/efeitos dos fármacos , Camundongos , Linhagem Celular Tumoral , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/síntese química , Anti-Inflamatórios/química , Sinergismo Farmacológico , Relação Estrutura-Atividade , Camundongos Endogâmicos BALB C , Ensaios de Seleção de Medicamentos Antitumorais
15.
J Am Soc Nephrol ; 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38687828

RESUMO

BACKGROUND: The therapeutic options for IgA nephropathy are rapidly evolving, but early diagnosis and targeted treatment remain challenging. We aimed to identify circulating plasma proteins associated with IgA nephropathy by proteome-wide mendelian randomization studies across multiple ancestry populations. METHODS: In this study, we applied Mendelian randomization and colocalization analyses to estimate the putative causal effects of 2615 proteins on IgA nephropathy in Europeans and 235 proteins in East Asians. Following two-stage network Mendelian randomization, multi-trait colocalization analysis and protein-altering variant annotation were performed to strengthen the reliability of the results. A protein-protein interaction network was constructed to investigate the interactions between the identified proteins and the targets of existing medications. RESULTS: Putative causal effects of 184 and 13 protein-disease pairs in European and East Asian ancestries were identified, respectively. Two protein-disease pairs showed shared causal effects across them (CFHR1 and FCRL2). Supported by the evidence from colocalization analysis, potential therapeutic targets were prioritized and four drug-repurposing opportunities were suggested. The protein-protein interaction network further provided strong evidence for existing medications and pathways that are known to be therapeutically important. CONCLUSIONS: Our study identified a number of circulating proteins associated with IgA nephropathy and prioritized several potential drug targets that require further investigation.

16.
Toxins (Basel) ; 16(3)2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38535787

RESUMO

Zearalenone (ZEN) is a non-steroidal estrogenic mycotoxin found in many agricultural products and can cause reproductive disorders, mainly affecting spermatogenesis in male animals. Rutin (RUT) is a natural flavonoid compound recognized for its significant antioxidant, anti-inflammatory and estrogenic properties. The present study aimed to determine the protective role of RUT against ZEN-induced reproductive toxicity in male mice. Twenty-four adult Kunming male mice were divided into four groups: control, RUT (500 mg/kg RUT), ZEN (10 mg/kg ZEN), ZEN + RUT (500 mg/kg RUT + 10 mg/kg ZEN), with six replicates per treatment. The results indicated that RUT mitigated ZEN-induced disruption in spermatogenic cell arrangement, decreased spermatozoa count, and increased sperm mortality in the testes. RUT significantly restored ZEN-induced reduction in T, FSH, LH, and E2 serum levels. Moreover, RUT mitigated ZEN-induced apoptosis by increasing the mRNA expression level of bcl-2, decreasing the mRNA expression level of kiss1-r, and decreasing the protein expression level of caspase 8 in reproductive tissues. These findings indicate the protective role of RUT against ZEN-induced reproductive toxicity in male mice by regulating gonadotropin and testosterone secretions to maintain normal spermatogenesis via the HPG axis, which may provide a new application direction for RUT as a therapeutic agent to mitigate ZEN-induced reproductive toxicity.


Assuntos
Zearalenona , Masculino , Camundongos , Animais , Rutina , Eixo Hipotalâmico-Hipofisário-Gonadal , Sêmen , Animais não Endogâmicos , Apoptose , RNA Mensageiro , Expressão Gênica
17.
ACS Nano ; 18(14): 9929-9941, 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38533847

RESUMO

The use of trivalent erbium (Er3+), typically embedded as an atomic defect in the solid-state, has widespread adoption as a dopant in telecommunication devices and shows promise as a spin-based quantum memory for quantum communication. In particular, its natural telecom C-band optical transition and spin-photon interface make it an ideal candidate for integration into existing optical fiber networks without the need for quantum frequency conversion. However, successful scaling requires a host material with few intrinsic nuclear spins, compatibility with semiconductor foundry processes, and straightforward integration with silicon photonics. Here, we present Er-doped titanium dioxide (TiO2) thin film growth on silicon substrates using a foundry-scalable atomic layer deposition process with a wide range of doping controls over the Er concentration. Even though the as-grown films are amorphous after oxygen annealing, they exhibit relatively large crystalline grains, and the embedded Er ions exhibit the characteristic optical emission spectrum from anatase TiO2. Critically, this growth and annealing process maintains the low surface roughness required for nanophotonic integration. Finally, we interface Er ensembles with high quality factor Si nanophotonic cavities via evanescent coupling and demonstrate a large Purcell enhancement (≈300) of their optical lifetime. Our findings demonstrate a low-temperature, nondestructive, and substrate-independent process for integrating Er-doped materials with silicon photonics. At high doping densities this platform can enable integrated photonic components such as on-chip amplifiers and lasers, while dilute concentrations can realize single ion quantum memories.

18.
Sci Total Environ ; 926: 171951, 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38537836

RESUMO

A remarkable progress has been made toward the air quality improvements over the Guangdong-Hong Kong-Macao Greater Bay Area (GBA) of China from 2017 to 2020. In this study, for the first time, the emission reductions of regional control measures together with the COVID-19 pandemic were considered simultaneously into the development of the GBA's emission inventories for the years of 2017 and 2020. Based on these collective emission inventories, the impacts of control measures, meteorological variations together with temporary COVID-19 lockdowns on the five major air quality index pollutants (SO2, NO2, PM2.5, PM10, and O3, excluding CO) were evaluated using the WRF-CMAQ and SMAT-CE model attainment assessment tool over the GBA region. Our results revealed that control measures in the Pearl River Delta (PRD) region affected significantly the GBA, resulting in pollutant reductions ranging from 48 % to 64 %. In contrast, control measures in Hong Kong and Macao contributed to pollutant reductions up to 10 %. In PRD emission sectors, stationary combustion, on-road, industrial processes and dust sectors stand out as the primary contributors to overall air quality improvements. Moreover, the COVID-19 pandemic during period I (Jan 23-Feb 23) led to a reduction of NO2 concentration by 7.4 %, resulting in a negative contribution (disbenefit) for O3 with an increase by 2.4 %. Our findings highlight the significance of PRD control measures for the air quality improvements over the GBA, emphasizing the necessity of implementing more refined and feasible manageable joint prevention and control policies.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , COVID-19 , Poluentes Ambientais , Humanos , Poluentes Atmosféricos/análise , Poluição do Ar/prevenção & controle , Poluição do Ar/análise , Material Particulado/análise , Melhoria de Qualidade , Dióxido de Nitrogênio , Pandemias/prevenção & controle , Monitoramento Ambiental/métodos , COVID-19/epidemiologia , COVID-19/prevenção & controle , Controle de Doenças Transmissíveis , China/epidemiologia
19.
Int Immunopharmacol ; 131: 111920, 2024 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-38522142

RESUMO

The exact pathogenesis of IgA nephropathy (IgAN) is complex and so far, not well defined. Since it has been shown that microbial infections could induce high levels of type I interferon (IFN-I) and there is an evident link between mucosal infection and gross hematuria in IgAN, we hypothesized that IFN-I may play a role in the pathogenic process. In this study, we investigated the type I interferon status in IgAN based on the expression of 17 IFN-regulated genes (IRGs) in whole blood from 59 IgAN patients in a cross-sectional study, of which 34 patients followed longitudinally. Analysis of the IFN-score showed that there was a significant elevated IFN-score in the IgAN patients compared with healthy controls (n = 28, p = 9.80 × 10-3), and we observed an elevated IFN-score in the group with less tubular atrophy/interstitial fibrosis (p = 1.07 × 10-2) and with a lower proportion of mesangial hypercellularity (p = 1.23 × 10-2). In the longitudinal analysis, Cox regression analysis revealed that a higher IFN level was associated with a better renal outcome in IgAN after adjustments for gender and age (hazard ratio, 0.90; 95 % confidence interval, 0.81 to 0.97; p = 4.20 × 10-2). In conclusion, our finding suggested that IFN score may represent a novel type of biomarker in IgAN, which requires further exploration on its mechanism and therapeutic targeting.


Assuntos
Glomerulonefrite por IGA , Interferon Tipo I , Humanos , Glomerulonefrite por IGA/genética , Glomerulonefrite por IGA/tratamento farmacológico , Interferon Tipo I/genética , Interferon Tipo I/uso terapêutico , Estudos Transversais , Prognóstico , Rim/patologia
20.
BMC Genomics ; 25(1): 280, 2024 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-38493091

RESUMO

BACKGROUND: Atrial fibrillation (AF) is a prevalent arrhythmic condition resulting in increased stroke risk and is associated with high mortality. Electrolyte imbalance can increase the risk of AF, where the relationship between AF and serum electrolytes remains unclear. METHODS: A total of 15,792 individuals were included in the observational study, with incident AF ascertainment in the Atherosclerosis Risk in Communities (ARIC) study. The Cox regression models were applied to calculate the hazard ratio (HR) and 95% confidence interval (CI) for AF based on different serum electrolyte levels. Mendelian randomization (MR) analyses were performed to examine the causal association. RESULTS: In observational study, after a median 19.7 years of follow-up, a total of 2551 developed AF. After full adjustment, participants with serum potassium below the 5th percentile had a higher risk of AF relative to participants in the middle quintile. Serum magnesium was also inversely associated with the risk of AF. An increased incidence of AF was identified in individuals with higher serum phosphate percentiles. Serum calcium levels were not related to AF risk. Moreover, MR analysis indicated that genetically predicted serum electrolyte levels were not causally associated with AF risk. The odds ratio for AF were 0.999 for potassium, 1.044 for magnesium, 0.728 for phosphate, and 0.979 for calcium, respectively. CONCLUSIONS: Serum electrolyte disorders such as hypokalemia, hypomagnesemia and hyperphosphatemia were associated with an increased risk of AF and may also serve to be prognostic factors. However, the present study did not support serum electrolytes as causal mediators for AF development.


Assuntos
Fibrilação Atrial , Humanos , Fibrilação Atrial/epidemiologia , Fibrilação Atrial/genética , Fatores de Risco , Magnésio , Análise da Randomização Mendeliana , Cálcio , Potássio , Fosfatos , Eletrólitos , Estudo de Associação Genômica Ampla/métodos
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