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1.
Bioanalysis ; 14(5): 307-316, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35195039

RESUMO

Aim: HCP002, a phosphate-modified derivative of voriconazole, can improve solubility without using the nephrotoxic solubilizer, sulfobutylether-ß-cyclodextrin. To study pharmacokinetics in humans, LC-MS/MS methods to quantify HCP002 in human plasma and urine were developed and validated. Method: After protein precipitation by acetonitrile containing voriconazole-d3, HCP002 was separated on a ZORBAX SB-Aq column, and LCMS/MS analysis was performed in multi-response monitoring mode. Results: The analytical run time was 3 min. Linearity was observed over the ranges of 0.100-40.0 and 0.400-200 µg/ml in plasma and urine, respectively. Precision and accuracy were within acceptable limits. Sample stability was confirmed. Conclusion: Rapid and reproducible methods quantified HCP002 in urine, and plasma samples were established.


Assuntos
Plasma , Espectrometria de Massas em Tandem , Cromatografia Líquida/métodos , Humanos , Reprodutibilidade dos Testes , Espectrometria de Massas em Tandem/métodos
2.
Food Chem Toxicol ; 165: 113119, 2022 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-35537648

RESUMO

Di-2-ethylhexyl phthalate (DEHP) has been widely used in many fields (agricultural products, medical instruments, and food packing). As an environmental contaminant, DEHP has a negative impact on human and animal health, and thus toxicity caused by DEHP is increasingly serious health concern. Nevertheless, DEHP-induced liver damage in quail remains unclear. To investigate the mechanism of liver damage caused by DEHP, male quail were treated with DEHP (250, 500, and 750 mg/kg) by gavage. Notably, DEHP exposure results in increased blood lipids and the accumulation of triglycerides (TG), total cholesterol (TC), and non-esterified fatty acid (NEFA) in the liver. Histopathological analysis showed that steatosis and inflammatory cell infiltration were observed in the liver tissue of quails exposed to DEHP. The results of Oil Red O staining displayed that DEHP induced lipid storage in the liver. Moreover, DEHP induced lipid metabolism disorders by activating the LXR/SREBP-1c and PPARα/γ signaling pathway. DEHP exposure obviously caused the up-regulation of pro-inflammatory cytokines (NF-κB, IL-6, IL-8, IL-1ß, and TNF-a). This study showed that DEHP could induce lipid metabolism disorders and inflammatory response via LXR/SREBP-1c/PPARα/γ and NF-κB signaling pathways.

3.
Artigo em Inglês | MEDLINE | ID: mdl-35552653

RESUMO

OBJECTIVES: To define the pattern of body composition and alteration after treatment of patients with newly diagnosed idiopathic inflammatory myopathies (IIM) using dual-energy X-ray absorptiometry (DXA). METHODS: DXA was used to obtain regional and whole-body measurements of fat mass (FM) and lean tissue mass (LTM) in 50 patients with newly diagnosed IIM and matched controls. The DXA indices of FM and LTM were calculated. The analyses included correlations between DXA indices and clinical parameters (manual muscle test [MMT], myositis damage index [MDI], myositis intention-to-treat activities index [MITAX], handgrip, percentage forced vital capacity [%FVC], and creatine kinase level), comparison between patients with IIM and controls, comparison between IIM subgroups, receiver operating characteristic (ROC) analysis, and comparison of body composition before and after treatment. RESULTS: DXA LTM measurements were significantly correlated with MMT, MDI-muscle, handgrip strength, and %FVC. Patients with IIM had decreased LTM of the upper limbs and appendicular region. Male patients with IIM had significantly decreased LTM in the upper and lower limbs, whereas female patients with IIM had significantly decreased LTM in the upper limbs. Patients with IIM with anti-SRP seropositivity had lower LTM than patients with anti-SRP seronegativity. In ROC analysis, the DXA LTM indices presented good diagnostic values for distinguishing patients with newly diagnosed IIM from healthy controls. After treatment, the LTM of the upper limbs and appendicular region significantly increased. CONCLUSION: DXA is an attractive method for the evaluation of patients with newly diagnosed IIM as well as a new way of monitoring disease conditions.

4.
J Asian Nat Prod Res ; : 1-7, 2022 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-35579284

RESUMO

A chemical study of 90% ethanol extract of the barks of Juglans cathayensis resulted in the isolation of three new nortriterpenoids, jugcathenoids A-C (1-3). The structures of the new compounds were elucidated by spectroscopic analysis (NMR, IR, UV, and MS). The isolated nortriterpenoids were tested in vitro for cytotoxic activities against 6 pancreatic cell lines. As a result, compounds 1-3 exhibited some cytotoxic activities against all the tested tumor cell lines with IC50 values less than 50 µM.

5.
Eur Radiol ; 2022 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-35579712

RESUMO

OBJECTIVES: Cancer chemotherapy potentially increases the risk of myocardial ischemia. This study assessed myocardial microvascular function by cardiac magnetic resonance (CMR) first-pass perfusion in patients treated with chemotherapy for gynecologic malignancies. METHODS: A total of 81 patients treated with chemotherapy for gynecologic malignancies and 39 healthy volunteers were prospectively enrolled and underwent CMR imaging. Among the patients, 32 completed CMR follow-up, with a median interval of 6 months. The CMR sequences comprised cardiac cine, rest first-pass perfusion, and late gadolinium enhancement. RESULTS: There were no significant differences in the baseline characteristics between the patients and normal controls (all p > 0.05). Compared with the normal controls, the patients had a lower myocardial perfusion index (PI) (13.62 ± 2.01% vs. 12% (11 to 14%), p = 0.001) but demonstrated no significant variation with an increase in the number of chemotherapy cycles at follow-up (11.79 ± 2.36% vs. 11.19 ± 2.19%, p = 0.234). In multivariate analysis with adjustments for clinical confounders, a decrease in the PI was independently associated with chemotherapy treatment (ß = - 0.362, p = 0.002) but had no correlation with the number of chemotherapy cycles (r = - 0.177, p = 0.053). CONCLUSION: Myocardial microvascular dysfunction was associated with chemotherapy treatment in patients with gynecologic malignancies, and can be assessed and monitored by rest CMR first-pass perfusion. KEY POINTS: • Chemotherapy was associated with but did not aggravate myocardial microvascular dysfunction in patients with gynecologic malignancies. • Rest CMR first-pass perfusion is an ideal modality for assessing and monitoring alterations in myocardial microcirculation during chemotherapy treatment.

6.
JAMA Netw Open ; 5(5): e2212681, 2022 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-35579895

RESUMO

Importance: COVID-19 has required universities to rapidly develop vaccination policies for students and staff, yet little is known about the preferences of these individuals toward vaccination. Objective: To quantify student and staff preferences for COVID-19 vaccination at a university in Hong Kong. Design, Setting, and Participants: A cross-sectional online survey study was conducted from July 20 to September 21, 2021, before the announcement of a campus-wide vaccine mandate. A survey of 42 451 eligible university students and staff used discrete-choice experiment methods to quantify 7 attributes of COVID-19 vaccination: risk of a mild or moderate adverse event after vaccination, risk of a severe adverse event after vaccination, efficacy against COVID-19 infection, efficacy against severe manifestation of COVID-19 infection, duration of protection after vaccination, incentive for completing vaccination, and out-of-pocket costs. Main Outcomes and Measures: A mixed logit regression model was used to estimate the preferences of attributes for COVID-19 vaccines and marginal willingness to pay (mWTP) adjusted for background characteristics, role, vaccination, and COVID-19 infection status of family or friends, adverse event status after vaccination among family and friends of participants, and scenario block. Results: Among 42 451 eligible university students and staff invited, 3423 individuals completed the survey (mean [SD] age, 27.1 [9.9] years; 2053 [60.0%] women). Participants included 2506 students (73.2%) and 917 staff (26.8%), with a response rate of 8.1%. Quarantine-free travel was preferred (ß = 0.86; 95% CI, 0.72-0.99; mWTP: $235.9; 95% CI, $190.3-$294.2), followed by efficacy against any COVID-19 infection (ß = 0.30; 95% CI, 0.29-0.32; mWTP: $84.1; 95% CI, $71.8-$100.8), against severe manifestation of COVID-19 infection (ß = 0.25; 95% CI, 0.24-0.27; mWTP: $69.7; 95% CI, $465-$653), and risk of severe adverse events following vaccination (ß = -0.24; 95% CI, -0.27 to -0.21; mWTP: -$66.8; 95% CI, -$81.5 to -$55.3). Participants were less concerned about protection duration (ß = 0.17; 95% CI, 0.15-0.18; mWTP: $46.0; 95% CI, $38.6-$56.2) and risk of mild to moderate adverse events (ß = -0.12; 95% CI, -0.13 to -0.10; mWTP: -$32.7; 95% CI, -$41.2 to -$26.4). Conclusions and Relevance: Preference of all attributes were significant and were considered important by the participants for vaccine decision-making. Insights drawn could assist policy makers in future vaccination decisions, such as campus vaccine mandate and requirement of a third dose.

7.
Cardiovasc Diabetol ; 21(1): 69, 2022 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-35524215

RESUMO

BACKGROUND: Heart failure with reduced ejection fraction (HFrEF) is a major health burden worldwide with high morbidity and mortality. Comorbidities of HFrEF complicate treatment and lead to poor prognosis, among which hypertension (HTN) and diabetes mellitus (DM) are common and frequently cooccur. DM was found to have additive effects on cardiac function and structure in hypertensive patients, while its effects on the HFrEF cohort in the context of HTN remain unclear. METHODS: A total of 171 patients with HFrEF were enrolled in our study, consisting of 51 HFrEF controls, 72 hypertensive HFrEF patients (HTN-HFrEF [DM-]) and 48 hypertensive HFrEF patients with comorbid DM (HTN-HFrEF [DM+]). Cardiac MRI-derived left ventricular (LV) strains, including global radial (GRPS), circumferential (GCPS) and longitudinal (GLPS) peak strain, and remodeling parameters were measured and compared among groups. The determinants of impaired LV function and LV remodeling in HFrEF patients were investigated by multivariable linear regression analyses. RESULTS: Despite a similar LV ejection fraction, patients in the HTN-HFrEF (DM+) and HTN-HFrEF (DM-) groups showed a higher LV mass index and LV remodeling index than those in the HFrEF control group (all p < 0.05). Compared with the HTN-HFrEF (DM-) and HFrEF control groups, the HTN-HFrEF (DM+) group exhibited the most severe GLPS impairment (p < 0.001). After adjustment for covariates in HFrEF patients, DM was found to be an independent determinant of impaired LV strains in all three directions (GRPS [ß = - 0.189; p = 0.011], GCPS [ß = 0.217; p = 0.005], GLPS [ß = 0.237; p = 0.002]). HTN was associated with impaired GLPS (ß = 0.185; p = 0.016) only. However, HTN rather than DM was associated with LV remodeling in HFrEF patients in the multivariable regression analysis (p < 0.05). CONCLUSIONS: DM aggravated LV longitudinal dysfunction in hypertensive HFrEF patients without further changes in LV remodeling, indicating that HFrEF patients with comorbid HTN and DM may have a hidden high-risk phenotype of heart failure that requires more advanced and personalized management.


Assuntos
Diabetes Mellitus , Insuficiência Cardíaca , Hipertensão , Disfunção Ventricular Esquerda , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/epidemiologia , Insuficiência Cardíaca/diagnóstico por imagem , Insuficiência Cardíaca/epidemiologia , Humanos , Hipertensão/complicações , Hipertensão/diagnóstico , Hipertensão/epidemiologia , Imageamento por Ressonância Magnética , Volume Sistólico , Disfunção Ventricular Esquerda/diagnóstico por imagem , Disfunção Ventricular Esquerda/epidemiologia , Função Ventricular Esquerda , Remodelação Ventricular
8.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 47(2): 202-210, 2022 Feb 28.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-35545410

RESUMO

OBJECTIVES: The plateau environment is characterized by low oxygen partial pressure, leading to the reduction of oxygen carrying capacity in alveoli and the reduction of available oxygen in tissues, and thus causing tissue damage. Cilostazol is a phosphodiesterase III inhibitor that has been reported to increase the oxygen release of hemoglobin (Hb) in tissues. This study aims to explore the anti-hypoxic activity of cilostazol and its anti-hypoxic effect. METHODS: A total of 40 male BALB/C mice were randomly divided into a low-dose cilostazol (6.5 mg/kg) group, a medium-dose (13 mg/kg) group, a high-dose (26 mg/kg) group, and a control group. The atmospheric airtight hypoxia experiment was used to investigate the anti-hypoxic activity of cilostazol and to screen the optimal dosage. Twenty-four male Wistar rats were randomly divided into a normoxia control group, a hypoxia model group, an acetazolamide (22.33 mg/kg) group, and a cilostazol (9 mg/kg) group. After 3 days of hypoxia in the 4 010 m high altitude, blood from the abdominal aorta was collected to determine blood gas indicators, the levels of IL-6 and TNF-α in plasma were determined by enzyme-linked immunosorbent assay, and the levels of malondialdehyde (MDA), superoxide dismutase (SOD), and glutataione (GSH) were measured. The degree of pathological damage for rat tissues was observed with HE staining. RESULTS: Compared with the control group, the survival time of mice in the low, medium, and high dose group of cilostazol was significantly prolonged, and the survival time of mice in the medium dose group was the longest, with an extension rate at 29.34%, so the medium dose was the best dose. Compared with the hypoxia model group, the P50 (oxygen partial pressure at Hb oxygen saturation of 50%) value of rats in the cilostazol group was significantly increased by 1.03%; Hb and Hct were significantly reduced by 8.46% and 8.43%, and the levels of IL-6 and TNF-α in plasma were reduced by 50.65% and 30.77%. The MDA contents in heart, brain, lung, liver, and kidney tissues were reduced by 37.12%, 29.55%, 25.00%, 39.34%, and 21.47%, respectively. The SOD activities were increased by 94.93%, 9.14%, 9.42%, 13.29%, and 20.80%, respectively. The GSH contents were increased by 95.24%, 28.62%, 28.57%, 20.80%, and 44.00%, respectively. The results of HE staining showed that compared with the hypoxia model group, cilostazol significantly improved the damage of heart, lung, and kidney tissues in rats after hypoxia. CONCLUSIONS: Cilostazol can significantly improve the oxidative stress and inflammatory reaction caused by rapid altitude hypoxia, and it has a significant protective effect on tissue damage caused by hypoxia, suggesting that it has obvious anti-hypoxic activity.


Assuntos
Doença da Altitude , Animais , Cilostazol/farmacologia , Cilostazol/uso terapêutico , Hipóxia/tratamento farmacológico , Interleucina-6/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Estresse Oxidativo , Oxigênio , Ratos , Ratos Wistar , Superóxido Dismutase/metabolismo , Fator de Necrose Tumoral alfa/farmacologia
9.
Plant Dis ; 2022 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-35549450

RESUMO

Pear (Pyrus pyrifolia (Burm.f.) Nakai) is widely planted in China and plays a key role in economy. In the autumn of 2016, five pear fruits showing symptoms of brown rot (Fig. 1A) were found in a Suancun farmer market in Kunming, Yunnan Province, China (25°02' N; 102°42' E). The incidence of this disease in postharvest pear fruits ranged from 2 % to 5 % in this city. Three fruit samples were taken to run further tests. The decayed area of the fruit was soft, brown, slightly sunken, and circular. Carrot baiting was used to isolate the pathogen from symptomatic tissue (Moller et al. 1968). Primary isolates were made by transferring ascospore drops from the tips of the perithecia formed on the carrot discs onto PDA plates. Single ascospore cultures were generated by transferring single ascospores to potatoe dextrose agar (PDA) plates. Cultures were incubated 7 days at 25°C with a 12-h light/12-h dark cycle. In culture, mycelium was initially white, turned to a shallow celadon and gradually to grey-greenish later. Measurements were made 10 days after the formation of perithecia. Six pure cultures (lik-1~lik-6) were stored at -80 °C in 15% glycerol and stored at the State Key Laboratory for Conservation and Utilization of Bio-Resources of Yunnan Agricultural University. Four isolates (lik-1~lik-4) produced ascomatal bases that were submerged in the agar. Bases (Fig. 1E) were globose, black, 192.15 to 250.81 µm wide, 192.94 to 251.31 µm long, and had straight necks terminating in ostiolar hyphae (Fig. 1F) that were divergent, hyaline, and 74.19 to 116.33 µm long. Asci were not observed. Ascospores (Fig. 1I) were ovoid, hat-shaped (dimensions 3.2 to 5.1 × 2.3 to 4.6 µm). Conidiogenous cells were with enteroblastic conidium ontogeny, flask-shaped or tubular, 65.3 to 130.6 µm long, and produced cylindrical, straight aseptate conidia (8.5 to 18 × 2.5 to 3.5 µm) (Fig.1 G). All isolates produced dark brown, 10.07 to 13.08 ×8.51 to 11.64 µm aleurioconidia (Fig. 1H). Two (lik-1, lik-3) of six isolates were used for molecular identification and genomic DNA was extracted using the CTAB method (Lee & Taylor 1990). The primers ITS1 and ITS4, EF1F and EF2R were used to amplify and sequence the rDNA-ITS and TEF-1α regions (Thorpe et al. 2005; Jacobs et al. 2004). The sequences of rDNA-ITS of the isolates lik-1 and lik-3 (GenBank Accession Nos: MF153994, MF153993) showed 99.49% similarity to AF395679 (C. fimbriata isolate CMW2219). Additionally, the TEF-1α sequences of isolates lik-1 and lik-3 (GenBank Accession Nos: KY708912, KY708915) showed 100% identify to MF347676 (C. fimbriata isolate CM18). Based on symptoms, morphological characteristics, rDNA-ITS and TEF1-α sequence analysis and pathogenicity, this fungus was identified as C. fimbriata. Pathogenicity tests were conducted using 2 isolates (lik-1, lik-3) and repeated three times. Three fresh pear fruits were disinfected with 75% alcohol, then they were wounded with a 2 mm hole punch and inoculated with 200 µL conidia suspension of the fungus (approximately 2.0 × 106 conidia / mL) on the fruit surface. After inoculation pear fruits were incubated in boxes at 25°C with a relative humidity of 80% and a 12-h light / 12-h dark cycle. Three pear fruits that served as controls were wounded by punching a 2 mm hole into the skin and inoculated with 200 µL sterile distilled water. Symptoms of rot were observed one week after inoculation (Fig.1 B). The diameter of the external lesion varied from 1.5 to 2.5 cm, on average 1.9 cm. When pears were cut, the white pulp had turned black and was rotting (Fig.1 C, D). The pathogen re-isolated from all inoculated symptomatic tissue was identical to the isolates originally obtained from the pear fruits at the market by morphology and ITS analysis. No symptoms developed on the control. The pathogenicity assay showed that C. fimbriata was pathogenic on pears. To our knowledge, this is the first report of C. fimbriata on pear in China. The spread of this disease may pose a threat to pear quality in China and further studies could be performed to determine effective disease management strategies.

10.
Int J Mol Sci ; 23(9)2022 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-35562870

RESUMO

Porcine circovirus 2 (PCV2) and pseudorabies virus (PRV) are two important pathogens in the pig industry. PCV2 or PRV infection can induce endoplasmic reticulum stress (ERS) and unfolded protein response (UPR). However, the effect of PCV2 and PRV coinfection on the ERS and UPR pathways remains unclear. In this study, we found that PRV inhibited the proliferation of PCV2 mainly at 36 to 72 hpi, while PCV2 enhanced the proliferation of PRV in the middle stage of the infection. Notably, PRV is the main factor during coinfection. The results of the transcriptomic analysis showed that coinfection with PCV2 and PRV activated cellular ERS, and upregulated expressions of the ERS pathway-related proteins, including GRP78, eIF2α, and ATF4. Further research indicated that PRV played a dominant role in the sequential infection and coinfection of PCV2 and PRV. PCV2 and PRV coinfection induced the ERS activation via the PERK-eIF2α-ATF4-CHOP axis and IRE1-XBP1-EDEM pathway, and thus may enhance cell apoptosis and exacerbate the diseases.

11.
Eur J Pharmacol ; 925: 174977, 2022 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-35513019

RESUMO

Cardiovascular disorders and associated renal diseases account for the main cause of morbidity and mortality worldwide, necessitating the development of novel effective approaches for the prevention and treatment of cardiorenal diseases. Mammalian sirtuins (SIRTs) function as nicotinamide adenine dinucleotide (NAD+)-dependent protein/histone deacetylases. Seven members of SIRTs share a highly invariant catalytic core domain responsible for the specific enzymatic activity. Intriguingly, the broad distribution of SIRTs and alternative isoforms implicate its distinct functions in diverse cardiac and renal cells and tissue types. Notably, SIRT7 has been shown to exert beneficial effects in cardiorenal physiology and pathophysiology via modulation of senescence, DNA damage repair, ribosomal RNA synthesis, protein biosynthesis, angiogenesis, apoptosis, superoxide generation, cardiorenal metabolism, and dysfunction. Furthermore, SIRT7 has emerged as a critical modulator of a broad range of cellular activities including oxidative stress, inflammation response, endoplasmic reticulum stress, and mitochondrial homeostasis, which are all of great significance in postponing the progression of cardiorenal diseases. More importantly, SIRT7 has been implicated in cardiorenal hypertrophy, fibrosis, remodeling, heart failure, atherosclerosis as well as renal acid-base and electrolyte homeostasis as an essential regulator. In this article, we focus on the involvement in cardiorenal physiology and pathophysiology, diverse actions and underlying mechanisms of the SIRT7 signaling, highlighting its updated research progress in heart failure, atherosclerosis, diabetic nephropathy and other cardiorenal diseases. Targeting SIRT7 signaling could be potentially exploited as a therapeutic strategy aiming to prevent and treat cardiorenal diseases.

12.
Psychiatry Res ; 313: 114582, 2022 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-35526421

RESUMO

OBJECTIVE: Many studies have reported the important role of serum levels of short-chain fatty acids (SCFAs) in lipid metabolism and cognitive dysfunction. This study investigated the role of plasma lipids and SCFAs on cognitive functioning in drug- naïve first episode schizophrenia. METHODS: This study recruited 44 schizophrenia inpatients and 35 healthy controls. Plasma lipid metabolism was characterized using standard enzymatic methods and an automated analyzer. Serum levels of SCFAs were measured by Gas chromatography mass spectrometry (GC-MS). Cognitive performance was evaluated by the MATRICS Consensus Cognitive Battery (MCCB). RESULTS: The patient group showed significantly higher serum levels of total SCFAs, acetic acid, acetic acid/ propionic acid ratio, and poorer cognitive scores compared with the control group (p's < 0.05). Within the patient group, the lipid levels were positively associated with acetic acid/ propionic acid ratio (p's < 0.05). Furthermore, multiple regression analysis revealed that the interactions of LDL level × acetic acid/ propionic acid ratio was a significant predictor of the MCCB working memory, and processing speed subscale scores within the patient group. CONCLUSIONS: Cognitive dysfunction and abnormal serum levels of SCFAs occur in the early phase of schizophrenia. Lipid metabolism and serum levels of SCFAs might be, both independently or interactively, associated with cognitive dysfunction in schizophrenia.

13.
Front Oncol ; 12: 863340, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35530326

RESUMO

Objective: Whether fasting insulin (FI) plays a role in cancer risk remains unclear. This study aimed to investigate the association between FI and cancer risk and to explore its potential mediator role in the association between type 2 diabetes mellitus (T2DM) and cancer. Methods: Two-sample Mendelian randomization (TSMR) analysis was performed to evaluate the effect of FI on overall and 14 site-specific cancers using genome-wide association study (GWAS) summary-level data from Meta-Analyses of Glucose and Insulin-related traits Consortium (MAGIC) and consortia of 14 site-specific cancers. The primary MR approach was conducted by using the random-effect inverse-variance weighted (IVW) method, and sensitivity analyses were implemented by adopting weighted-median, weighted-mode, MR-Egger, and MR-PRESSO tests. Polygenic risk score analysis was executed by using individual-level data from UK Biobank to validate the findings from TSMR analyses. Multivariable Mendelian randomization (MVMR) was carried out to estimate the mediation effect of FI on the association between T2DM and cancer. Results: TSMR study suggested that genetically determined high FI levels were associated with increased risk of colorectal cancer (odds ratio (OR) = 1.87, 95% CI: 1.23-2.84, p = 0.003) and endometrial cancer (OR = 1.89, 95% CI: 1.08-3.01, p = 0.008), but not associated with overall cancer risk or the other 12 studied cancer sites. Polygenic risk score analysis successfully replicated the association between genetic liability to high FI levels and the increased risk of colorectal and endometrial cancers. MVMR and MR mediation analyses detected an intermediary effect of FI and quantified that FI mediated 21.3% of the association between T2DM and endometrial cancer. Conclusions: This study demonstrated that FI levels are associated with the risk of colorectal and endometrial cancers, and FI was found to play an intermediary role in the association between T2DM and endometrial cancer. The associations between FI and other cancers need to be further studied.

14.
Front Microbiol ; 13: 791248, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35531284

RESUMO

To screen, prepare, identify, and evaluate the activities of natural antioxidants for treating chronic diseases caused by oxidative stress. Two algal proteins, namely ZD10 and ZD60, precipitated with 10 and 60% (NH4)2SO4 were extracted from red algae Eucheuma cottonii (E. cottonii) and hydrolyzed using five proteolytic enzymes. The results showed that ZD60 played the most significant role in the enhancement of 2,2-diphenyl-1-picrylhydrazyl radical (DPPH⋅) scavenging activity (25.91 ± 0.24%) among all protein hydrolysates. Subsequently, six antioxidant peptides (EP1-EP6) were isolated from the papain hydrolysate of ZD60 by ultrafiltration and chromatography methods. Their amino acid sequences were identified as Thr-Ala (EP1), Met-Asn (EP2), Tyr-Ser-Lys-Thr (EP3), Tyr-Ala-Val-Thr (EP4), Tyr-Leu-Leu (EP5), and Phe-Tyr-Lys-Ala (EP6) with molecular weights of 190.21, 263.33, 497.55, 452.51, 407.51, and 527.62 Da, respectively. Of which, EP3, EP4, EP5, and EP6 showed strong scavenging activities on DPPH⋅, hydroxyl radical (HO⋅), and superoxide anion radical (O- 2⋅). Moreover, EP4 and EP5 could significantly protect human umbilical vein endothelial cells (HUVECs) from H2O2-induced oxidative damage by increasing the levels of antioxidant enzyme systems including superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) to reduce the levels of reactive oxygen species (ROS) (60.51 and 51.74% of model group) and malondialdehyde (MDA) (75.36 and 64.45% of model group). In addition, EP4 and EP5 could effectively inhibit H2O2-induced apoptosis by preventing HUVECs from early apoptosis to late apoptosis. These results indicated that the antioxidant peptides derived from E. cottonii, especially EP4 and EP5, could serve as the natural antioxidants applied in pharmaceutical products to treat chronic cardiovascular diseases caused by oxidative damage, such as coronary heart disease, atherosclerosis, etc.

15.
Zhongguo Zhong Yao Za Zhi ; 47(8): 2008-2014, 2022 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-35531715

RESUMO

Chinese medicine dispensing granules, the result of the efforts to transform Chinese medicinal decoction pieces in China, features portability and ease of storage. Thus, it is destined to be an indispensible dosage form in the modernization drive of Chinese medicine. The Announcement on Ending the Pilot Project of Chinese Medicine Dispensing Granules was released in February 2021 and relevant regulations went into force in November 2021, which marks the a new journey for the development of Chinese medicine dispensing granules and the beginning of the "post-pilot era". However, it faces the challenges in quality and standard. This study reviewed the history of Chinese medicine dispensing granules, analyzed the technical progress, market, and main problems in development, and proposed suggestions and prospects for its development in the "post-pilot era", which is expected to serve as a reference for its industry development and rational use.


Assuntos
Medicamentos de Ervas Chinesas , Medicina Tradicional Chinesa , China , Medicamentos de Ervas Chinesas/uso terapêutico , Desenvolvimento Industrial , Projetos Piloto
16.
Zhen Ci Yan Jiu ; 47(4): 290-7, 2022 Apr 25.
Artigo em Chinês | MEDLINE | ID: mdl-35532365

RESUMO

OBJECTIVE: To observe the effect of mild moxibustion on monocyte chemotaxis protein 1 (MCP-1)/matrix metalloproteinase 2 (MMP-2)/transforming growth factor ß1 (TGF-ß1) pro-inflammatory signal loop in senile rats, so as to explore its mechanisms underlying improving vascular aging (VA). METHODS: Twenty-four male VA SD rats were randomized into senium (VA) control, medication and moxibustion groups, and other 8 young SD rats (aged 2 months) were used as the young control group. The VA model was established by intraperitoneal injection of D-galactose (300 mg·kg-1·d-1) once daily for 4 weeks, and verified by serum total testosterone (TT) and free testosterone (FT) levels. For rats of the moxibustion group, mild moxibustion was applied to bilateral "Shenshu"(BL23) and "Guanyuan"(CV4) for 20 min, once a day, 5 days a week for 8 weeks. Rats of the medication group were treated by intraperitoneal injection of testosterone propionate (7 mg·kg-1·[3 d]-1) once daily for 8 weeks except weekends, and rats of the senium control and young control groups treated by intraperitoneal injection of the same dose of normal saline, once daily for 8 weeks except weekends. The duration of exhausted swimming (DES) before and after the treatment was recorded. H.E. staining and Masson staining were used to observe histopathological changes and collagen fiber content of the thoracic aortic tissue, respectively. The contents of serum TT, FT and angiotensin 2 (Ang Ⅱ) were determined by ELISA. The immunoactivity of aortic MCP-1 was detected by immunohistochemistry, and the expression levels of aortic MCP-1, MMP-2 and TGF-ß1 were detected by Western blot. RESULTS: Compared with the young control group, the levels of DES, serum TT and FT contents were significantly decreased (P<0.01), while those of serum AngⅡ and collagen fiber contents, aortic MCP-1 immunoactivity and MMP-2, TGF-ß1 and MCP-1 protein expression considerably increased in the senium control group (P<0.01). After the interventions, the decreased levels of DES, serum TT and FT contents and the increased levels of serum AngⅡ, collagen fiber contents, aortic MCP-1 immunoactivity and MMP-2, TGF-ß1 and MCP-1 protein expression were reversed in both medication and moxibustion groups (P<0.01, P<0.05). The therapeutic effect of mild moxibustion was significantly superior to that of medication in down-regulating the aortic collagen fiber, serum AngⅡ contents and MCP-1 immunoactivity and protein expression (P<0.05). H.E. staining showed thickened endometrium and disordered arrangement of vascular smooth muscles of the aorta in the senium group, and thinner endometrium and regular and ordered arrangement of aortic vascular smooth muscles in both moxibustion and medication groups. CONCLUSION: Mild moxibustion may improve vascular aging in senescence rats, which is possibly by suppressing vascular MCP-1/MMP-2/TGF-ß1 pro-inflammatory signal loop.


Assuntos
Moxibustão , Envelhecimento , Animais , Colágeno , Feminino , Masculino , Metaloproteinase 2 da Matriz/genética , Ratos , Ratos Sprague-Dawley , Testosterona , Fator de Crescimento Transformador beta1/genética
17.
Org Biomol Chem ; 2022 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-35537202

RESUMO

A selective arylation of donor-acceptor diazo compounds with aniline derivatives catalyzed by Lewis acidic boranes is developed. This simple reaction protocol provides an efficient method for the synthesis of diarylacetates under metal-free conditions.

18.
Front Psychiatry ; 13: 788677, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35546939

RESUMO

Preclinical and clinical studies have suggested that fibroblast growth factor (FGF) system contributed to the onset and development of schizophrenia (SCZ). However, there was no strong clinical evidence to link an individual FGF with SCZ. In this study, we aim to measure blood FGF9 levels in the patients with SCZ with and/or without medication, and test whether FGF9 has a potential to be a biomarker for SCZ. We recruited 130 patients with SCZ and 111 healthy individuals, and the ELISA and qRT-PCR assays were used to measure serum FGF9 levels in the participants. ELISA assay demonstrated that serum FGF9 protein levels were dramatically reduced in first-episode, drug-free patients, but not in chronically medicated patients when compared to healthy control subjects. Further analysis showed that treatment of the first-episode, drug-free SCZ patients with antipsychotics for 8 weeks significantly increased the serum FGF9 levels. In addition, we found that blood FGF9 mRNA levels were significantly lower in first-onset SCZ patients than controls. Under the receiver operating characteristic curve, the optimal cutoff values for FGF9 protein level as an indicator for diagnosis of drug-free SCZ patients was projected to be 166.4 pg/ml, which yielded a sensitivity of 0.955 and specificity of 0.86, and the area under the curve was 0.973 (95% CI, 0.954-0.993). Furthermore, FGF9 had good performance to discriminate between drug-free SCZ patients and chronically medicated patients, the optimal cutoff value for FGF9 concentration was projected to be 165.035 pg/ml with a sensitivity of 0.86 and specificity of 0.919, and the AUC was 0.968 (95% CI, 0.944, 0.991). Taken together, our results for the first time demonstrated the dysregulation of FGF9 in SCZ, and FGF9 has the potential to be served as a biomarker for SCZ.

19.
Front Cardiovasc Med ; 9: 814505, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35548430

RESUMO

Objective: Obesity is a prominent public health problem that has increased cardiovascular mortality risks. However, the specific effects of obesity, independent of comorbidities, on cardiac structure and function have not been well clarified, especially those effects on the right ventricle (RV). Cardiovascular magnetic resonance (CMR) tissue tracking can assess detailed RV mechanical features. This study aimed to evaluate RV strain using CMR in uncomplicated obese adults and assess its association with fat distributions. Methods: A total of 49 obese patients and 30 healthy controls were included. The RV global systolic function and strain parameters based on CMR were assessed. Body fat distributions were measured with dual X-ray absorptiometry. RV function indices of obese patients were compared with those of healthy controls. Correlations among related body fat distribution parameters and RV function indices were conducted with multivariable linear regression. Results: Compared with healthy controls, the obese group had impaired RV strain with lower global longitudinal peak strain (PS), longitudinal peak systolic strain rate (PSSR), circumferential and longitudinal peak diastolic strain rates (PDSR) (all P < 0.05), while LV and RV ejection fractions were not significantly different between the two groups (P > 0.05). Multivariable linear regression analysis demonstrated that android fat% was independently associated with longitudinal PS (ß = -0.468, model R2 = 0.219), longitudinal PDSR (ß = -0.487, model R2 = 0.237), and circumferential PSSR (ß = -0.293, model R2 = 0.086). Trunk fat% was independently associated with longitudinal PSSR (ß = -0.457, model R2 = 0.209). In addition, the strongest correlations of circumferential PDSR were BMI and gynoid fat% (ß = -0.278, ß = 0.369, model R2 = 0.324). Conclusions: Extensive subclinical RV dysfunction is found in uncomplicated obese adults. BMI, as an index of overall obesity, is independently associated with subclinical RV dysfunction. In addition, central obesity (android fat and trunk fat distributions) has a negative effect on subclinical RV function, while peripheral obesity (gynoid fat distribution) may have a positive effect on it. Clinical Trials Registration: Effect of lifestyle intervention on metabolism of obese patients based on smart phone software (ChiCTR1900026476).

20.
Front Genet ; 13: 831599, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35559027

RESUMO

The aim of this study was to locate SSTR5 polymorphisms and evaluate their association with growth traits in Hulun Buir sheep. The study followed up 884 Hulun Buir sheep from birth to 16 months of age, which were born in the same pasture and the same year, and a consistent grazing management strategy was maintained. The birth weight (BRW) was recorded at birth, and body weight (BW), body height (BH), body length (BL), chest circumference (ChC), chest depth (ChD), chest width (ChW), hip width (HW), and cannon circumference (CaC) were measured at 4 and 9 months of age. BW, BH, BL, ChD, HW, and CaC were also recorded at 16 months of age. Based on the growth traits, 233 sheep were selected as experimental animals. Sanger sequencing was performed, and seven single-nucleotide polymorphisms (SNPs) were identified. Association analyses of the SNPs and the growth traits were then conducted. Seven SNPs of the SSTR5 exhibited moderate polymorphism (0.25

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