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1.
Ther Drug Monit ; 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34610620

RESUMO

PURPOSE: P-glycoprotein, encoded by ABCB1 (or MDR1), may contribute to drug resistance in epilepsy by limiting gastrointestinal absorption and brain access to antiseizure medications (ASMs). The study aimed to evaluate the impact of ABCB1 polymorphisms on lacosamide (LCM) serum concentrations in Uygur pediatric epileptic patients. METHODS: The serum concentrations of LCM were determined by ultra-performance liquid chromatography, and the ABCB1 polymorphism was analyzed via polymerase chain reaction-fluorescence staining in situ hybridization. The chi-squared test and Fisher's exact test were used to analyze the allelic and genotypic distributions of ABCB1 polymorphisms between the drug-resistant and drug-responsive patient groups. Differences in steady-state and dose-corrected LCM serum concentrations between different genotypes were analyzed using the One-Way Analysis of Variance (ANOVA) and Mann-Whitney test. RESULTS: A total of 131 Uygur children with epilepsy were analyzed, and of them, 41 demonstrated drug resistance. The frequency of the GT genotype of ABCB1 G2677T/A was significantly higher in the drug-resistant group than that in the drug-responsive group (p < 0.05, OR = 1.966, 95% CI = 1.060-3.647). Patients with the G2677T/A- AT genotype had a statistically significantly lower concentration-to-dose (CD) value than patients with the G2677T/A-GG genotype (mean: 0.6 ± 0.2 vs 0.8 ± 0.5 µg/ml per mg/kg, p < 0.001). Significantly lower LCM serum concentrations were observed in ABCB1 C3435T CT and TT genotype carriers than those in the CC carriers (p = 0.008 and p = 0.002), and a significantly lower LCM CD value was observed in ABCB1 C3435T CT genotype carriers than that in the CC carriers (p = 0.042). CONCLUSION: ABCB1 G2677T/A and C3435T polymorphisms may affect LCM serum concentrations and treatment efficacy in Uygur pediatric patients with epilepsy, leading to drug resistance in pediatric patients.

2.
Artigo em Inglês | MEDLINE | ID: mdl-34657424

RESUMO

A reliable and sensitive detection approach for SARS-CoV 2 is essential for timely infection diagnosis and transmission prevention. Here, a two-dimensional (2D) metal-organic framework (MOF)-based photoelectrochemical (PEC) aptasensor with high sensitivity and stability for SARS-CoV 2 spike glycoprotein (S protein) detection was developed. The PEC aptasensor was constructed by a plasmon-enhanced photoactive material (namely, Au NPs/Yb-TCPP) with a specific DNA aptamer against S protein. The Au NPs/Yb-TCPP fabricated by in situ growth of Au NPs on the surface of 2D Yb-TCPP nanosheets showed a high electron-hole (e-h) separation efficiency due to the enhancement effect of plasmon, resulting in excellent photoelectric performance. The modified DNA aptamer on the surface of Au NPs/Yb-TCPP can bind with S protein with high selectivity, thus decreasing the photocurrent of the system due to the high steric hindrance and low conductivity of the S protein. The established PEC aptasensor demonstrated a highly sensitive detection for S protein with a linear response range of 0.5-8 µg/mL with a detection limit of 72 ng/mL. This work presented a promising way for the detection of SARS-CoV 2, which may conduce to the impetus of clinic diagnostics.

3.
Plant Physiol ; 186(4): 2051-2063, 2021 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-34618105

RESUMO

The histone H3 family in animals and plants includes replicative H3 and nonreplicative H3.3 variants. H3.3 preferentially associates with active transcription, yet its function in development and transcription regulation remains elusive. The floral transition in Arabidopsis (Arabidopsis thaliana) involves complex chromatin regulation at a central flowering repressor FLOWERING LOCUS C (FLC). Here, we show that H3.3 upregulates FLC expression and promotes active histone modifications histone H3 lysine 4 trimethylation (H3K4me3) and histone H3 lysine 36 trimethylation (H3K36me3) at the FLC locus. The FLC activator FRIGIDA (FRI) directly mediates H3.3 enrichment at FLC, leading to chromatin conformation changes and further induction of active histone modifications at FLC. Moreover, the antagonistic H3.3 and H2A.Z act in concert to activate FLC expression, likely by forming unstable nucleosomes ideal for transcription processing. We also show that H3.3 knockdown leads to H3K4me3 reduction at a subset of particularly short genes, suggesting the general role of H3.3 in promoting H3K4me3. The finding that H3.3 stably accumulates at FLC in the absence of H3K36me3 indicates that the H3.3 deposition may serve as a prerequisite for active histone modifications. Our results reveal the important function of H3.3 in mediating the active chromatin state for flowering repression.

4.
Front Endocrinol (Lausanne) ; 12: 724822, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34594303

RESUMO

Objective: To clarify the relationship between serum urate (SU) decrease and visceral fat area (VFA) reduction in patients with gout. Methods: We retrospectively analyzed 237 male gout patients who had two sets of body composition and metabolic measurements within 6 months. Subjects included had all been treated with urate-lowering therapy (ULT) (febuxostat 20-80 mg/day or benzbromarone 25-50 mg/day, validated by the medical record). All patients were from the specialty gout clinic of The Affiliated Hospital of Qingdao University. The multiple linear regression model evaluated the relationship between change in SU [ΔSU, (baseline SU) - (final visit SU)] and change in VFA [ΔVFA, (baseline VFA) - (final visit VFA)]. Results: ULT resulted in a mean (standard deviation) decrease in SU level (464.22 ± 110.21 µmol/L at baseline, 360.93 ± 91.66 µmol/L at the final visit, p <0.001) accompanied by a decrease in median (interquartile range) VFA [97.30 (81.15-118.55) at baseline, 90.90 (75.85-110.05) at the final visit, p < 0.001]. By multiple regression model, ΔSU was identified to be a significant determinant variable of decrease in VFA (beta, 0.302; p = 0.001). Conclusions: The decrease in SU level is positively associated with reduced VFA. This finding provides a rationale for clinical trials to affirm whether ULT promotes loss of visceral fat in patients with gout.

5.
Exp Ther Med ; 22(5): 1271, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34594408

RESUMO

The underlying mechanism of cardiac hypertrophy has not yet been fully elucidated. The present study aimed to explore the function of transcription factor EC (TFEC) in mouse models of cardiac hypertrophy and to determine the underlying mechanism. Pressure-overload cardiac hypertrophy and angiotensin II (AngII) infusion-induced animal models of cardiac hypertrophy were established in vivo. The expression of TFEC was explored via western blotting. The results demonstrated that TFEC expression was significantly increased in the hearts of mice with pressure overload- and AngII-induced hypertrophy. Injection of rAd-short hairpin (sh)-TFEC significantly decreased the expression of TFEC in heart tissues compared with group injected with rAd-negative control (NC). Furthermore, the expression levels of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and ß-myosin heavy chain (ß-MHC) were increased in the hearts of AngII-treated mice; however, compared with rAd-NC transfection, transfection with rAd-sh-TFEC decreased the expression levels of ANP, BNP and ß-MHC. The results from echocardiographic analysis indicated that transfection with rAd-sh-TFEC improved the cardiac function of AngII-treated mice compared with transfection with rAd-NC. In addition, the AngII-induced increase in cardiomyocyte size could be reversed by TFEC knockdown in primary cardiomyocytes. The elevated expression levels of ANP, BNP and ß-MHC induced by AngII could be partially abolished following TFEC knockdown. The results from western blotting demonstrated that TFEC overexpression decreased the expression of phosphorylated AMP-activated protein kinase (AMPK)/acetyl-CoA carboxylase (ACC) but increased the expression of phosphorylated mechanistic target of rapamycin (mTOR). Furthermore, Compound C significantly suppressed the activation of AMPK/ACC but increased the activation of mTOR, even in primary cardiomyocytes transfected with rAd-sh-TFEC. In conclusion, the findings from this study demonstrated that TFEC was overexpressed in the hearts of mice with cardiac hypertrophy and that silencing TFEC may improve AngII-induced cardiac hypertrophy and dysfunction by activating AMPK/mTOR signaling.

6.
Int J Nanomedicine ; 16: 6719-6747, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34621124

RESUMO

Despite several recent advances, current therapy and prevention strategies for myocardial infarction are far from satisfactory, owing to limitations in their applicability and treatment effects. Nanoparticles (NPs) enable the targeted and stable delivery of therapeutic compounds, enhance tissue engineering processes, and regulate the behaviour of transplants such as stem cells. Thus, NPs may be more effective than other mechanisms, and may minimize potential adverse effects. This review provides evidence for the view that function-oriented systems are more practical than traditional material-based systems; it also summarizes the latest advances in NP-based strategies for the treatment and prevention of myocardial infarction.

7.
Zhongguo Zhen Jiu ; 41(9): 1017-20, 2021 Sep 12.
Artigo em Chinês | MEDLINE | ID: mdl-34491652

RESUMO

OBJECTIVE: To compare the therapeutic effect between cotton-moxibustion and compound flumetasone ointment, and observe the effect on quality of life in patients with chronic eczema. METHODS: A total of 66 patients with chronic eczema were randomized into an observation group (33 cases, 2 cases dropped off) and a control group (33 cases, 2 cases dropped off). In the observation group, cotton-moxibustion was adopted on target skin lesion, once a day, 3 cones a time. In the control group, external application of compound flumetasone ointment was given twice a day. The treatment for 3 weeks was required in the both groups. Before treatment and 1,2,3 weeks into treatment, scores of visual analogue scale (VAS), eczema area and severity index (EASI) and dermatology life quality index (DLQI) were observed, and the recurrence rate was evaluated in the follow-up one month after treatment. RESULTS: Compared before treatment, the VAS scores of 1,2,3 weeks into treatment, the EASI and DLQI scores of 2,3 weeks into treatment were decreased in the both groups (P<0.05), and those in the observation group were lower than the control group (P<0.05). The follow-up recurrence rate in the observation group were lower than the control group (P<0.05). CONCLUSION: Cotton-moxibustion can effectively improve the pruritus symptom, skin lesion and quality of life in the patients with chronic eczema, the therapeutic effect is superior to the external application of compound flumetasone ointment.


Assuntos
Eczema , Moxibustão , Pontos de Acupuntura , Eczema/tratamento farmacológico , Humanos , Qualidade de Vida , Recidiva , Resultado do Tratamento
8.
J Transl Int Med ; 9(2): 98-113, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34497749

RESUMO

Background and Objective: HuangZhi YiShen Capsule (HZYS) is a Chinese patent herbal drug that protects kidney function in diabetic kidney disease (DKD) patients. However, the pharmacologic mechanisms of HZYS remain unclear. This study would use network pharmacology to explore the pharmacologic mechanisms of HZYS. Methods: Chemical constituents of HZYS were obtained through the Traditional Chinese Medicine Systems Pharmacology Database (TCMSP) and literature search. Potential targets of HZYS were identified by using the TCMSP and the SwissTarget Prediction databases. DKD-related target genes were collected by using the Online Mendelian Inheritance in Man, Therapeutic Target Database, GeneCards, DisGeNET, and Drugbank databases. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were carried out to further explore the mechanisms of HZYS in treating DKD. Molecular docking was conducted to verify the potential interactions between the prime compounds and the hub genes. Results: 179 active compounds and 620 target genes were obtained, and 571 common targets were considered potential therapeutic targets. The top 10 main active compounds of HZYS were heparin, quercetin, kaempferol, luteolin, methyl14-methylpentadecanoate, methyl (Z)-11-hexadecenoate, 17-hydroxycorticosterone, 4-pregnene-17α, 20ß, 21-triol-3, 11-dione, wogonin, and hydroxyecdysone. Hub signaling pathways by which HZYS treating DKD were PI3K-Akt, MAPK, AGE-RAGE in diabetic complications, TNF, and apoptosis. The top 10 target genes associated with these pathways were IL6, MAPK1, AKT1, RELA, BCL2, JUN, MAPK3, MAP2K1, CASP3, and TNF. Quercetin and Luteolin were verified to have good binding capability with the hub potential targets IL6, MAPK1, AKT1 through molecular docking. Conclusion: HZYS appeared to treat DKD by regulating the inflammatory, oxidative stress, apoptotic, and fibrosis signaling pathways. This study provided a novel perspective for further research of HZYS.

9.
Artigo em Inglês | MEDLINE | ID: mdl-34505252

RESUMO

In this study, the marine microalgae Skeletonema costatum and Nitzschia closterium were exposed to different forms of copper, such as a metal salt (Cu2+), a nano-metal (nano-Cu), and nano-metal oxide (nano-CuO). During a 96-h exposure to nanoparticles (NPs) and salt, the cell number, Cu2+ concentration in the culture medium, morphology, and intracellular amino acids were measured to assess the toxicity of the copper materials and the toxicity mechanism of the NPs. As results, the toxicity of Cu2+, nano-Cu, and nano-CuO to marine phytoplankton decreased in order. The EC50 values of Cu2+ and nano-Cu for S. costatum and N. closterium ranged from 0.356 to 0.991 mg/L and 0.663 to 2.455 mg/L, respectively. Nano-Cu inhibits the growth of marine phytoplankton by releasing Cu2+; however, nano-CuO is harmful to microalgae because of the effect of NPs. The secretion of extracellular polymeric substances by microalgae could also affect the toxicity of nano-Cu and nano-CuO to microalgae. S. costatum was more sensitive to copper than N. closterium. Cu2+, nano-Cu, and nano-CuO all reduced per-cell amino acids and the total output of algae-derived amino acids by affecting the growth of the phytoplankton. This study helps to understand the risk assessment of nano-Cu and nano-CuO to marine microalgae.

10.
Cancer Lett ; 521: 178-195, 2021 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-34492331

RESUMO

With the identification of "negative immune regulation" defects in the immune system and the continuous improvement of immunotherapy, natural killer cells (NK) have received more attention, especially as tools in combined immunotherapy. Carbon ions (12C6+) have become the ideal radiation for combined immunotherapy due to their significant radiobiological advantages and synergistic effects. The purpose of this study was to explore the NK cell-mediated cytotoxicity pathway and related mechanisms in lung cancer induced by carbon ion irradiation. KLRK1, which specifically encodes the NKG2D receptor, was significantly correlated with the prognosis, clinical stage, functional status of NK cells, and the immune microenvironment of lung cancer, as shown by bioinformatics analysis. Based on RNA-seq data of Lewis lung cancer in C57BL/6 mice, carbon ion irradiation was found to significantly induce Klrk1 gene expression and activate the NKG2D/NKG2D-Ls pathway. The Treg inhibition pathway combined with carbon ion radiotherapy could significantly increase the infiltration and function of NK cells in the tumor microenvironment of lung cancer and prolong the survival time of C57BL/6 mice. In conclusion, carbon ions have significant radiobiological advantages, especially under conditions of combined immunotherapy. Carbon ions combined with Treg inhibitors can significantly improve the infiltration and functional status of NK cells.

11.
Planta ; 254(4): 78, 2021 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-34536142

RESUMO

MAIN CONCLUSION: 51 MdbZIP genes were identified from the apple genome by bioinformatics methods. MhABF-OE improved tolerance to saline-alkali stress in Arabidopsis, indicating it is involved in positive regulation of saline-alkali stress response. Saline-alkali stress is a major abiotic stress limiting plant growth all over the world. Members of the bZIP family play an important role in regulating gene expression in response to many kinds of biotic and abiotic stress, including salt stress. According to the transcriptome data, 51 MdbZIP genes responding to saline-alkali stress were identified in apple genome, and their gene structures, conserved protein motifs, phylogenetic analysis, chromosome localization, and promoter cis-acting elements were analyzed. Based on transcriptome data analysis, a MdbZIP family gene (MD15G1081800), which was highly expressed under stress, was selected to isolate and named as MhABF. Expression profile analysis by quantitative real-time PCR confirmed that the expression of MhABF in the leaves of Malus halliana was 10.6-fold higher than that of the control (0 days) after 2 days of stress. Then an MhABF gene was isolated from apple rootstock M. halliana. CaMV35S promoter drived MhABF gene expression vector was constructed to infect Arabidopsis with Agrobacterium-mediated infection. And overexpression MhABF gene plants were obtained. Compared with wild type, transgenic plants grew better under saline-alkali stress and the MhABF-OE lines showed higher chlorophyll content, POD, SOD and CAT activity, which indicated that they had strong resistance to stress. These results indicate that MhABF plays an important role in plant resistance to saline-alkali stress, which lays a foundation for further study on the functions in apple.


Assuntos
Arabidopsis , Malus , Arabidopsis/genética , Arabidopsis/metabolismo , Regulação da Expressão Gênica de Plantas , Genoma de Planta/genética , Malus/genética , Malus/metabolismo , Filogenia , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Estresse Fisiológico/genética
12.
Lipids Health Dis ; 20(1): 116, 2021 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-34563206

RESUMO

BACKGROUND: Dyslipidemia is a predisposing factor for coronary heart disease (CHD). High-intensity statin therapy is recommended as secondary prevention. ABCB1 and SLCO1B1 genes influence the efficacy and safety of statins. Xinjiang is a multi-ethnic area; however, little is known about the prevalence of dyslipidemia and gene polymorphisms of ABCB1 and SLCO1B1 in minority groups with CHD. OBJECTIVE: To measure levels of lipid and apolipoprotein and the prevalence of dyslipidemia and gene polymorphisms of ABCB1, SLCO1B1 in Han, Uygur, Kazak, Hui, Tatar, Kirgiz, and Sibe populations with CHD in Xinjiang. METHODS: This descriptive retrospective study compares lipid levels in ethnic groups using Kruskal-Wallis test or analysis of variance. The study compared gene polymorphisms and the prevalence of dyslipidemia among different ethnic groups using the chi-square test. The lipid profiles in plasma were measured before lipid-lowering therapy using commercially available kits. Genotyping of SLCO1B1 and ABCB1 variants was performed using sequencing by hybridization. RESULTS: A total of 2218 patients were successfully screened, including 1044 Han, 828 Uygur, 113 Kazak, 138 Hui, 39 Tatar, 36 Kirgiz, and 20 Sibe patients. The overall mean age was 61.8 ± 10.8 years, and 72.5% of participants were male. Dyslipidemia prevalence in these ethnic groups was 42.1, 49.8, 52.2, 40.6, 48.7, 41.7, and 45.0%, respectively. The prevalence of dyslipidemia, high total cholesterol (TC), high triglycerides (TG), and high low density lipoprotein cholesterol (LDL-C) differed significantly among the groups (P = 0.024; P < 0.001; P < 0.001; P < 0.001, respectively). For the Han group, high LDL-C, high TC, and high TG prevalence differed significantly by gender (P = 0.001, P = 0.022, P = 0.037, respectively). The prevalence of high TC, high TG, and low high density lipoprotein cholesterol (HDL-C) differed significantly by gender in the Uygur group (P = 0.006, P = 0.004, P < 0.001, respectively). The prevalence of high TC in Hui patients significantly differed by gender (P = 0.043). These findings suggest that polymorphisms in ABCB1 and C3435T differ significantly across ethnicities (P < 0.001). CONCLUSIONS: The prevalences of dyslipidemia, high TC, high TG, and high LDL-C in Han, Uygur, Kazak, Hui, Tatar, Kirgiz, and Sibe CHD patients in Xinjiang differed concerning ethnicity. Ethnic, gender, and lifestyle were the key factors that affected the lipid levels of the population. The prevalence of polymorphisms of ABCB1 and C3435T significantly differed across ethnicities. These findings will aid the selection of precision lipid-lowering medications and prevention and treatment of CHD according to ethnicity in Xinjiang.

13.
Eur Radiol ; 2021 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-34519862

RESUMO

OBJECTIVE: Sonographic features are associated with pathological and immunohistochemical characteristics of triple-negative breast cancer (TNBC). To predict the biological property of TNBC, the performance using quantitative high-throughput sonographic feature analysis was compared with that using qualitative feature assessment. METHODS: We retrospectively reviewed ultrasound images, clinical, pathological, and immunohistochemical (IHC) data of 252 female TNBC patients. All patients were subgrouped according to the histological grade, Ki67 expression level, and human epidermal growth factor receptor 2 (HER2) score. Qualitative sonographic feature assessment included shape, margin, posterior acoustic pattern, and calcification referring to the Breast Imaging Reporting and Data System (BI-RADS). Quantitative sonographic features were acquired based on the computer-aided radiomics analysis. Breast cancer masses were manually segmented from the surrounding breast tissues. For each ultrasound image, 1688 radiomics features of 7 feature classes were extracted. The principal component analysis (PCA), least absolute shrinkage and selection operator (LASSO), and support vector machine (SVM) were used to determine the high-throughput radiomics features that were highly correlated to biological properties. The performance using both quantitative and qualitative sonographic features to predict biological properties of TNBC was represented by the area under the receiver operating characteristic curve (AUC). RESULTS: In the qualitative assessment, regular tumor shape, no angular or spiculated margin, posterior acoustic enhancement, and no calcification were used as the independent sonographic features for TNBC. Using the combination of these four features to predict the histological grade, Ki67, HER2, axillary lymph node metastasis (ALNM), and lymphovascular invasion (LVI), the AUC was 0.673, 0.680, 0.651, 0.587, and 0.566, respectively. The number of high-throughput features that closely correlated with biological properties was 34 for histological grade (AUC 0.942), 27 for Ki67 (AUC 0.732), 25 for HER2 (AUC 0.730), 34 for ALNM (AUC 0.804), and 34 for LVI (AUC 0.795). CONCLUSION: High-throughput quantitative sonographic features are superior to traditional qualitative ultrasound features in predicting the biological behavior of TNBC. KEY POINTS: • Sonographic appearances of TNBCs showed a great variety in accordance with its biological and clinical characteristics. • Both qualitative and quantitative sonographic features of TNBCs are associated with tumor biological characteristics. • The quantitative high-throughput feature analysis is superior to two-dimensional sonographic feature assessment in predicting tumor biological property.

14.
Molecules ; 26(17)2021 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-34500694

RESUMO

Nitrogen-rich porous networks with additional polarity and basicity may serve as effective adsorbents for the Lewis electron pairing of iodine molecules. Herein a carbazole-functionalized porous aromatic framework (PAF) was synthesized through a Sonogashira-Hagihara cross-coupling polymerization of 1,3,5-triethynylbenzene and 2,7-dibromocarbazole building monomers. The resulting solid with a high nitrogen content incorporated the Lewis electron pairing effect into a π-conjugated nano-cavity, leading to an ultrahigh binding capability for iodine molecules. The iodine uptake per specific surface area was ~8 mg m-2 which achieved the highest level among all reported I2 adsorbents, surpassing that of the pure biphenyl-based PAF sample by ca. 30 times. Our study illustrated a new possibility for introducing electron-rich building units into the design and synthesis of porous adsorbents for effective capture and removal of volatile iodine from nuclear waste and leakage.

15.
3 Biotech ; 11(9): 415, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34485008

RESUMO

Phytic acid is abundant in seeds, roots and stems of plants, it acts as an anti-nutrient in food and feed industry, since it affects the absorption of nutrients by humans and monogastric animals. Furthermore, phosphorus produced through its decomposition by microorganisms can cause environmental pollution. Phytase degrades phytic acid generating precursors of inositol that can be used in clinical practice; in addition, phytase treatment can minimize the anti-nutritional effect of phytic acid. The use of phytase synthesized from Bacillus is more advantageous due to its high activity. Additionally, its good heat resistance under neutral conditions greatly fills the gap of commercial utilization of acid phytase. In this review, we summarize the latest research results on Bacillus phytase, including its physiological and biochemical characteristics, molecular structure information, calcium effects on its catalytic activity and stability, its catalytic mechanism and molecular modification.

16.
Ann Palliat Med ; 2021 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-34498481

RESUMO

BACKGROUND: To evaluate the major cardiovascular events of febuxostat compared to allopurinol for the treatment of gout or asymptomatic hyperuricemia. METHODS: Relevant studies published until August 15, 2020 were identified by a systematic search of the PubMed and Wiley Online Library databases. Any controlled clinical trial, randomised controlled trial (RCT), retrospective cohort study or open label trial (OLT) comparing febuxostat in patients with gout or hyperuricemia with allopurinol. The quality of all identified studies was assessed based on Cochrane Collaboration's risk of bias tool. Odds ratios (OR) were calculated with random effects and reported with corresponding 95% confidence intervals (CI). RESULTS: Eighteen studies were ultimately included in the analysis, among them 6 articles mentioned serum uric acid (sUA) level before and after treatment, 14 articles mentioned major cardiovascular events, 5 articles mentioned cardiovascular death, 6 articles mentioned skin reactions, 6 articles mentioned musculoskeletal and connective tissue signs and symptoms, 4 articles mentioned joint-related signs and symptoms, 6 articles mentioned upper respiratory infection, 5 articles mentioned gastrointestinal reaction and 7 articles mentioned all-cause mortality. The febuxostat group showed significantly lower sUA levels than allopurinol group (MD =-0.83, 95% CI: -1.22 to -0.44, P<0.0001, I2 =98%). There was no markedly difference between the febuxostat and allopurinol (OR 1.01, 95% CI: 0.83 to 1.23, P=0.84, I2 =95%) in the major cardiovascular events. The occurrence of skin reactions of febuxostat was significantly fewer than allopurinol (OR 0.55, 95% CI: 0.42 to 0.73, P<0.0001, I2 =49%). Regarding to occurrence of CV death, musculoskeletal and connective tissue signs and symptoms, febuxostat group was higher than allopurinol group. However, among patients with gout or hyperuricemia, treatment with febuxostat resulted in other adverse reactions, including all-causes mortality similar to those associated with allopurinol. CONCLUSIONS: The limitation of the study was the included studies show high heterogeneity in regard to their design. There was no difference in the incidence of major cardiovascular events between febuxostat and allopurinol, and febuxostat was better in lowering uric acid and has less adverse skin reactions than allopurinol, but the risk of CV death of febuxostat was higher than allopurinol.

17.
Chem Biodivers ; : e2100672, 2021 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-34519420

RESUMO

Two new oleanane-triterpenoid saponins, clinograsaponins A (1) and B (2), together with twelve known ones (3-14), were isolated from the whole herb of Clinopodium gracile (Bentham) Matsumura. Their structures were determined by spectroscopic analysis and chemical method. All the isolated compounds were evaluated for their activities against ATP-citrate lyase (ACLY) and nuclear factor kappa B (NF-κB).

18.
Oncol Lett ; 22(5): 769, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34589148

RESUMO

Dishevelled-2 (DVL2) has been proven to be involved in the tumorigenesis of several human cancers, such as colorectal cancer, lung cancer, prostate cancer, etc. However, its role in pancreatic ductal adenocarcinoma (PDAC) remains unclear. The present study investigated the effects of aberrantly expressed DVL2 on PDAC. A total of 97 pancreatic cancer (PC) samples and 85 adjacent normal samples were obtained from patients who were histopathologically diagnosed with primary PDAC. The present study demonstrated that DVL2 expression was upregulated in PDAC tissues and was positively associated with advanced clinical stage and lymph node metastasis in patients with PDAC. In addition, patients with high expression of DVL2 had a shorter overall survival rate compared with those with low expression. To elucidate the role of DVL2 in PDAC, lentivirus-mediated short hairpin RNA was used to silence DVL2 and its physiological function was analyzed in CFPAC-1 and PANC-1 cells. The results indicated that DVL2 downregulation significantly impaired its oncogenic functions including cell proliferation, migration, invasion and epithelial-mesenchymal transition. Furthermore, DVL2 knockdown inhibits the proliferation and invasion of PC cells in vivo. In addition, co-immunoprecipitation assays revealed that DVL2 interacted with ß-catenin; knockdown of DVL2 reduced the expression level of ß-catenin and inhibited ß-catenin translocation into the nucleus. In conclusion the findings of the present study suggested that DVL2 may be a potential therapeutic target in the treatment of PDAC.

19.
Asia Pac J Clin Nutr ; 30(3): 446-456, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34587704

RESUMO

BACKGROUND AND OBJECTIVES: As an endocrine organ, the mass of skeletal muscle is closely related to human health. The present study aimed to investigate the relationship between regional skeletal muscle and nonalcoholic fatty liver disease (NAFLD) in Chinese elders. METHODS AND STUDY DESIGN: A total of 1,328 participants (579 males and 749 females), aged 65 to 96 years were recruited between March to November 2020 in Qingdao, China. Of these, 400 cases and 400 healthy controls, matched by gender and age (±3 years), were included in the study. Skeletal muscle mass was measured by bioelectrical impedance analysis, and body weight was adopted to standardize skeletal muscle mass to obtain skeletal muscle mass indexes. RESULTS: Inverse associations were observed for trunk muscle mass index (TMI) (OR=0.42; 95% CI: 0.19, 0.93; p for trend=0.083) and leg skeletal muscle mass index (LMI) (OR=0.41; 95% CI: 0.18, 0.97; p for trend=0.012) with NAFLD risk after adjustment for age, body mass index, glucose, total cholesterol, triglyceride, low density lipoprotein cholesterol, high density lipoprotein cholesterol, dietary intakes of energy, carbohydrate, protein and fat, smoking, alcohol drinking, education and physical activity. Dose-response analysis indicated that per standard deviation increment of LMI was associated with 23% (95%CI: 0.63, 0.95) reduction of NAFLD risk. CONCLUSIONS: The present study demonstrates that higher TMI and LMI are associated with a lower NAFLD risk.

20.
Cell Stem Cell ; 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34551362

RESUMO

Extracellular vesicles (EVs) transfer complex biologic material between cells. However, the role of this process in vivo is poorly defined. Here, we demonstrate that osteoblastic cells in the bone marrow (BM) niche elaborate extracellular vesicles that are taken up by hematopoietic progenitor cells in vivo. Genotoxic or infectious stress rapidly increased stromal-derived extracellular vesicle transfer to granulocyte-monocyte progenitors. The extracellular vesicles contained processed tRNAs (tiRNAs) known to modulate protein translation. 5'-ti-Pro-CGG-1 was preferentially abundant in osteoblast-derived extracellular vesicles and, when transferred to granulocyte-monocyte progenitors, increased protein translation, cell proliferation, and myeloid differentiation. Upregulating EV transfer improved hematopoietic recovery from genotoxic injury and survival from fungal sepsis. Therefore, EV-mediated tiRNA transfer provides a stress-modulated signaling axis in the BM niche distinct from conventional cytokine-driven stress responses.

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