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1.
Liver Int ; 2024 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-39082260

RESUMO

BACKGROUND: Dysregulation of bile acids (BAs), as important signalling molecules in regulating lipid and glucose metabolism, contributes to the development of non-alcoholic fatty liver disease (NAFLD). However, static BA profiles during fasting may obscure certain pathogenetic aspects. In this study, we investigate the dynamic alterations of BAs in response to an oral glucose tolerance test (OGTT) among children with NAFLD. METHODS: We recruited 230 subjects, including children with overweight/obesity, or complicated with NAFLD, and healthy controls. Serum BAs, 7-hydroxy-4-cholesten-3-one (C4) and fibroblast growth factor 19 (FGF19) were quantified during OGTT. Clinical markers related to liver function, lipid metabolism and glucose metabolism were assessed at baseline or during OGTT. FINDINGS: Conjugated BAs increased while unconjugated ones decreased after glucose uptake. Most BAs were blunted in response to glucose in NAFLD (p > .05); only glycine and taurine-conjugated chenodeoxycholic acid (CDCA) and cholic acid (CA) were responsive (p < .05). Primary BAs were significantly increased while secondary BAs were decreased in NAFLD. C4 and FGF19 were significantly increased while their ratio FGF19/C4 ratio was decreased in NAFLD. The dynamic pattern of CDCA and taurine-conjugated hyocholic acid (THCA) species was closely correlated with glucose (correlation coefficient r = .175 and -.233, p < .05), insulin (r = .327 and -.236, p < .05) and c-peptide (r = .318 and -.238, p < .05). Among which, CDCA was positively associated with liver fat content in NAFLD (r = .438, p < .05). Additionally, glycochenodeoxycholic acid (GCDCA), CDCA and THCA were potential biomarkers to discriminate paediatric NAFLD from healthy controls and children with obesity. INTERPRETATION: This study provides novel insights into the dynamics of BAs during OGTT in paediatric NAFLD. The observed variations in CDCA and HCA species were associated with liver dysfunction, dyslipidaemia and dysglycaemia, highlighting their potential roles as promising diagnostic and therapeutic targets in NAFLD.

2.
World J Gastroenterol ; 30(22): 2839-2842, 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38947289

RESUMO

Metabolic dysfunction-associated fatty liver disease (MAFLD) is the most prevalent chronic liver condition worldwide. Current liver enzyme-based screening methods have limitations that may missed diagnoses and treatment delays. Regarding Chen et al, the risk of developing MAFLD remains elevated even when alanine aminotransferase levels fall within the normal range. Therefore, there is an urgent need for advanced diagnostic techniques and updated algorithms to enhance the accuracy of MAFLD diagnosis and enable early intervention. This paper proposes two potential screening methods for identifying individuals who may be at risk of developing MAFLD: Lowering these thresholds and promoting the use of noninvasive liver fibrosis scores.


Assuntos
Fígado , Programas de Rastreamento , Hepatopatia Gordurosa não Alcoólica , Humanos , Fígado/patologia , Fígado/enzimologia , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Hepatopatia Gordurosa não Alcoólica/sangue , Programas de Rastreamento/métodos , Alanina Transaminase/sangue , Algoritmos , Biomarcadores/sangue , Cirrose Hepática/diagnóstico , Cirrose Hepática/sangue , Fatores de Risco , Diagnóstico Precoce
3.
Liver Int ; 2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-38963299

RESUMO

BACKGROUND AND AIMS: Lifestyle intervention is the mainstay of therapy for metabolic dysfunction-associated steatohepatitis (MASH), and liver fibrosis is a key consequence of MASH that predicts adverse clinical outcomes. The placebo response plays a pivotal role in the outcome of MASH clinical trials. Second harmonic generation/two-photon excitation fluorescence (SHG/TPEF) microscopy with artificial intelligence analyses can provide an automated quantitative assessment of fibrosis features on a continuous scale called qFibrosis. In this exploratory study, we used this approach to gain insight into the effect of lifestyle intervention-induced fibrosis changes in MASH. METHODS: We examined unstained sections from paired liver biopsies (baseline and end-of-intervention) from MASH individuals who had received either routine lifestyle intervention (RLI) (n = 35) or strengthened lifestyle intervention (SLI) (n = 17). We quantified liver fibrosis with qFibrosis in the portal tract, periportal, transitional, pericentral, and central vein regions. RESULTS: About 20% (7/35) and 65% (11/17) of patients had fibrosis regression in the RLI and SLI groups, respectively. Liver fibrosis tended towards no change or regression after each lifestyle intervention, and this phenomenon was more prominent in the SLI group. SLI-induced liver fibrosis regression was concentrated in the periportal region. CONCLUSION: Using digital pathology, we could detect a more pronounced fibrosis regression with SLI, mainly in the periportal region. With changes in fibrosis area in the periportal region, we could differentiate RLI and SLI patients in the placebo group in the MASH clinical trial. Digital pathology provides new insight into lifestyle-induced fibrosis regression and placebo responses, which is not captured by conventional histological staging.

4.
Obes Res Clin Pract ; 2024 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-39054194

RESUMO

OBJECTIVE: This study aimed to define the calf proportion index (CPI) and investigate its association with malnutrition and survival in overweight and obese patients with cancer. METHODS: This multicenter observational cohort study included 3499 patients diagnosed with cancer, including 3145 overweight and 354 obese individuals. The CPI was defined as the ratio of the cross-sectional area of the calf circumference (CC) to the body surface area (BSA). A CPI calculator that automatically calculated the CPI and survival probability based on the patient's sex, height, weight, and CC was developed. RESULTS: During a median follow-up of 44.1 months, 935 deaths were recorded. Receiver operating characteristic curves revealed that the CPI was better than CC and BSA as a predictor of survival, with AUCs for the 3-year mortality rate were 0.574, 0.553 and 0.529, respectively. In overweight and obese patients with cancer, the optimal CPI cut-off value was 0.65 % for men and 0.57 % for women. The Kaplan-Meier curve revealed that patients with a low CPI had lower survival. After adjusting confounding factors, a low CPI was an independent risk factor for overweight (hazard ratio [HR]: 1.29, 95 % confidence interval [CI]: 1.11-1.51, P < 0.001) and obesity (HR: 1.92, 95 % CI: 1.20-3.09, P = 0.007) in patients with cancer. The CPI exhibited significant prognostic value in patients with lung and digestive system cancers. The risk of malnutrition was significantly higher in patients with a low CPI (HR: 1.25, 95 % CI: 1.04-1.50, P = 0.019). CONCLUSIONS: The CPI is a useful prognostic indicator in overweight and obese patients with cancer, especially in obese patients.

5.
BMC Med ; 22(1): 278, 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38956533

RESUMO

BACKGROUND: APRI and FIB-4 scores are used to exclude clinically significant fibrosis (defined as stage ≥ F2) in patients with chronic viral hepatitis. However, the cut-offs for these scores (generated by Youden indices) vary between different patient cohorts. This study aimed to evaluate whether serum dithiothreitol-oxidizing capacity (DOC), i.e., a surrogate test of quiescin sulfhydryl oxidase-1, which is a matrix remodeling enzyme, could be used to non-invasively identify significant fibrosis in patients with various chronic liver diseases (CLDs). METHODS: Diagnostic performance of DOC was compared with APRI and FIB-4 for identifying significant fibrosis. ROC curve analyses were undertaken in: a) two chronic hepatitis B (CHB) cohorts, independently established from hospitals in Wenzhou (n = 208) and Hefei (n = 120); b) a MASLD cohort from Wenzhou hospital (n = 122); and c) a cohort with multiple CLD etiologies (except CHB and MASLD; n = 102), which was identified from patients in both hospitals. Cut-offs were calculated using the Youden index. All CLD patients (n = 552) were then stratified by age for ROC curve analyses and cut-off calculations. RESULTS: Stratified by CLD etiology or age, ROC curve analyses consistently showed that the DOC test was superior to APRI and FIB-4 for discriminating between clinically significant fibrosis and no fibrosis, when APRI and FIB-4 showed poor/modest diagnostic performance (P < 0.05, P < 0.01 and P < 0.001 in 3, 1 and 3 cohort comparisons, respectively). Conversely, the DOC test was equivalent to APRI and FIB-4 when all tests showed moderate/adequate diagnostic performances (P > 0.05 in 11 cohort comparisons). DOC had a significant advantage over APRI or FIB-4 scores for establishing a uniform cut-off independently of age and CLD etiology (coefficients of variation of DOC, APRI and FIB-4 cut-offs were 1.7%, 22.9% and 47.6% in cohorts stratified by CLD etiology, 2.0%, 26.7% and 29.5% in cohorts stratified by age, respectively). The uniform cut-off was 2.13, yielded from all patients examined. Surprisingly, the uniform cut-off was the same as the DOC upper limit of normal with a specificity of 99%, estimated from 275 healthy control individuals. Hence, the uniform cut-off should possess a high negative predictive value for excluding significant fibrosis in primary care settings. A high DOC cut-off with 97.5% specificity could be used for detecting significant fibrosis (≥ F2) with an acceptable positive predictive value (87.1%). CONCLUSIONS: This proof-of-concept study suggests that the DOC test may efficiently rule out and rule in significant liver fibrosis, thereby reducing the numbers of unnecessary liver biopsies. Moreover, the DOC test may be helpful for clinicians to exclude significant liver fibrosis in the general population.


Assuntos
Biomarcadores , Ditiotreitol , Cirrose Hepática , Humanos , Cirrose Hepática/diagnóstico , Cirrose Hepática/sangue , Masculino , Pessoa de Meia-Idade , Biomarcadores/sangue , Feminino , Adulto , Idoso , Oxirredução , Curva ROC , Estudos de Coortes , Oxirredutases atuantes sobre Doadores de Grupo Enxofre/sangue , Estudo de Prova de Conceito
8.
Chin Med Sci J ; 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38953223

RESUMO

Objective To explore the influence of Linggui Zhugan Decoction (LGZGD) on high glucose induced podocyte autophagy Methods LGZGD containing serum were prepared by intragastric administation of 4.2 g·kg-1 (low dose), 8.4 g·kg-1 (medium dose), and 12.6 g·kg-1 (high dose) LGZGD into SD rats respectively. MPC5 and AB8/13 cells were treated with 60 mmol/L glucose to establish diabetic nephropathy podocyte model in vitro. Podocytes, MPC5 and AB8.13, were divided into control group, high glucose group, low dose LGZGD group, medium dose LGZGD group, and high dose LGZGD group, respectively. For the three LGZGD groups, before LGZGD intervention, podocytes were treated with 60 mmol/L glucose for 3 days. After treated with LGZGD containing serum, cells were collected to analyze cell migration using Transwell assay, proliferation using CCK8, apoptosis and cell cycle using flow cytometry,, autophagosome formation using transmission electron microscopy, and expression levels of Beclin-1, Atg5, LC3II/I, and P62 proteins using western blot.Results Compared with the control group, the proliferation and migration of MPC5 and AB8.13 cells in high glucose group showed slightly decreased, whereas these parameters restored after intervention with low and medium concentrations of LGZGD, with the medium dose LGZGD having the best effect. Flow cytometry analysis showed that the medium dose LGZGD group had a lower apoptosis rate (P < 0.05) and higher survival rate (P > 0.05) compared to the high dose group. High glucose arrested podocytes in G1 phase, whereas LGZGD shifted podocytes from being predominant in G1 phase to increasing into G2. High dose LGZGD significanly reduced increased autophagosome formation due to high glucose in both podocytes (P < 0.05). Western blot analysis showed that Beclin-1, Atg5, LC3Ⅱ/Ⅰ, and P62 expressions were increased in MPC5 cells treated with high glucose, and reversed after adminstration of low and medium doses of LGZGD (P < 0.05). Conclusion LGZGD reduced apoptosis and enhanced autophagy in high glucose treated podocytes via regulating Beclin-1/LC3II/I/Atg5 expression.

9.
Sci Rep ; 14(1): 15811, 2024 07 09.
Artigo em Inglês | MEDLINE | ID: mdl-38982221

RESUMO

The Microsoft Kinect depth sensor, with its built-in software that automatically captures joint coordinates without markers, could be a potential tool for ergonomic studies. This study investigates the performance of Kinect in limb segment lengths using dual-energy X-ray absorptiometry (DXA) as a reference. Healthy children and adults (n = 76) were recruited for limb length measurements by Kinect and DXA. The results showed consistent ratios of arm, forearm, thigh, and leg lengths to height, which were 0.16, 0.14, 0.23, and 0.22 respectively, for both age groups and methods. Kinect exhibited perfect correlation among all limb lengths, indicating fixed proportions assumed by its algorithm. Comparing the two methods, there was a strong correlation (R = 0.850-0.985) and good to excellent agreement (ICC = 0.829-0.977), except for the right leg in adults, where agreement was slightly lower but still moderate (ICC = 0.712). The measurement bias between the methods ranged from - 1.455 to 0.536 cm. In conclusion, Kinect yields outcomes similar to DXA, indicating its potential utility as a tool for ergonomic studies. However, the built-in algorithm of Kinect assumes fixed limb proportions for individuals, which may not be ideal for studies focusing on investigating limb discrepancies or anatomical differences.


Assuntos
Absorciometria de Fóton , Humanos , Adulto , Masculino , Criança , Feminino , Absorciometria de Fóton/métodos , Adulto Jovem , Algoritmos , Software , Adolescente , Pessoa de Meia-Idade , Antropometria/métodos
10.
Angew Chem Int Ed Engl ; : e202412193, 2024 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-39022851

RESUMO

Transition-metal-catalyzed enantioselective transformations of aryl/aryl carbene are inherently challenging due to the difficulty in distinguishing between two arene rings in the reaction process thus remain largely less explored. The few successful examples reported so far, without exception, have all been catalyzed by Rh(II)-complexes. Herein, we describe our successful development of a novel cationic Rh(I)/chiral diene catalytic system capable of efficient enantioselective B-H and O-H insertions with diaryl diazomethanes, allowing the access to a broad range of gem-diarylmethine boranes and gem-diarylmethine ethers in good yields with high enantioselectivities. Notably, previously unattainable asymmetric diarylcarbene insertion into the O-H bond was achieved for the first time. A remarkable feature of this newly designed Rh(I)/diene catalyst bearing two ortho-amidophenyl substitutents is that it can distinguish between two arene rings of the diaryl carbene through a stereochemically selective control of π-π stacking interactions. DFT calculations indicate that the rotation-restricted conformation of Rh(I)/diene complex played an important role in the highly enantioselective carbene transformations. This work provides an interesting and unprecedented stereocontrol mode in diaryl metal carbene transformations.

11.
Huan Jing Ke Xue ; 45(7): 4206-4217, 2024 Jul 08.
Artigo em Chinês | MEDLINE | ID: mdl-39022967

RESUMO

In order to remedy the lack of research on the effect of "Grain for Green" on soil carbon (C) and nitrogen (N) distribution on slope soil in purple hilly areas of Sichuan Basin, China, a study was conducted on a long-term observation site established in the Wanan small watershed of Yanting Agro-ecological Experimental Station of Purple Soil, Chinese Academy of Sciences. The morphology, content, and storage of C and N in soil at different slope positions of farmland and the artificial forests in rehabilitated land with a history of approximately 30 years were compared. Our results showed that "Grain for Green" significantly increased soil organic carbon (SOC) content and SOC stock in all soil layers. The SOC stock of the surface layer (0-20 cm) increased by 25.86 t·hm-2, and the annual SOC stocks ratio was 0.89 t·hm-2. Soil total nitrogen (TN) content increased slightly but only in the 0-20 cm soil layer. Compared with those in sloping farmland, the differences in available C and N nutrients such as soil nitrate N (NO3--N), ammonia N (NH4+-N), and dissolved organic C (DOC) in the whole soil profile (0-70 cm) were basically not significant (P > 0.05). In addition, our research also found that slope position had significant effects on the contents of TN, SOC, NO3--N, NH4+-N, and DOC in farmland soil (P< 0.05). The variation trend of soil NO3--N, NH4+-N, and DOC contents along the slope was as follows: upper slope < middle slope < lower slope, whereas the soil TN and SOC contents were highest in the lower slope, followed by the upper slope and middle slope. The position of the slope had a significant impact only on DOC content in forest soil, which increased along the slope. This research indicated that when evaluating the impact of land use changes on soil C and N stocks in the purple soil hilly region, the influence of topographic factors cannot be ignored.

12.
JHEP Rep ; 6(7): 101066, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39022387

RESUMO

Background & Aims: Patients with nonalcoholic fatty liver disease (NAFLD)/metabolic dysfunction-associated steatotic liver disease (MASLD) face a multifaceted disease burden which includes impaired health-related quality of life (HRQL) and potential stigmatization. We aimed to assess the burden of liver disease in patients with NAFLD and the relationship between experience of stigma and HRQL. Methods: Members of the Global NASH Council created a survey about disease burden in NAFLD. Participants completed a 35-item questionnaire to assess liver disease burden (LDB) (seven domains), the 36-item CLDQ-NASH (six domains) survey to assess HRQL and reported their experience with stigmatization and discrimination. Results: A total of 2,117 patients with NAFLD from 24 countries completed the LDB survey (48% Middle East and North Africa, 18% Europe, 16% USA, 18% Asia) and 778 competed CLDQ-NASH. Of the study group, 9% reported stigma due to NAFLD and 26% due to obesity. Participants who reported stigmatization due to NAFLD had substantially lower CLDQ-NASH scores (all p <0.0001). In multivariate analyses, experience with stigmatization or discrimination due to NAFLD was the strongest independent predictor of lower HRQL scores (beta from -5% to -8% of score range size, p <0.02). Experience with stigmatization due to obesity was associated with lower Activity, Emotional Health, Fatigue, and Worry domain scores, and being uncomfortable with the term "fatty liver disease" with lower Emotional Health scores (all p <0.05). In addition to stigma, the greatest disease burden as assessed by LDB was related to patients' self-blame for their liver disease. Conclusions: Stigmatization of patients with NAFLD, whether it is caused by obesity or NAFLD, is strongly and independently associated with a substantial impairment of their HRQL. Self-blame is an important part of disease burden among patients with NAFLD. Impact and implications: Patients with nonalcoholic fatty liver disease (NAFLD), recently renamed metabolic dysfunction-associated steatotic liver disease (MASLD), may experience impaired health-related quality of life and stigmatization. Using a specifically designed survey, we found that stigmatization of patients with NAFLD, whether it is caused by obesity or the liver disease per se, is strongly and independently associated with a substantial impairment of their quality of life. Physicians treating patients with NAFLD should be aware of the profound implications of stigma, the high prevalence of self-blame in the context of this disease burden, and that providers' perception may not adequately reflect patients' perspective and experience with the disease.

13.
Phytochem Anal ; 2024 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-39072803

RESUMO

INTRODUCTION: The identification of Aucklandiae Radix (AR), Vladimiriae Radix (VR), and Inulae Radix (IR) based on traits and microscopic features is susceptible to the state of samples and the subjective awareness of personnel, and the identification based on a few or single chemical compositions is a cumbersome and time-consuming procedure and fails to rationally and effectively utilize the information of unknown components and is not specificity enough. OBJECTIVES: This study aimed to improve the identification efficiency, strengthen supervision, and realize digital identification of three Chinese medicines. Ultra-high-performance liquid chromatography with quadrupole time-of-flight mass spectrometry (UHPLC-QTOF-MS) combined with multivariate algorithms was used to explore the digital identification of AR, VR, and IR. MATERIALS AND METHODS: UHPLC-QTOF-MS was used to analyze AR, VR, and IR. The MS data combined with multivariate algorithms such as partial least squares discrimination analysis (PLS-DA) and artificial neural networks (ANNs) was used to filter important variables and data modeling. Finally, the optimal model was selected for the digital identification of three herbs. RESULTS: The results showed that three herbs can be distinguished on the whole level, and through feature screening, 591 characteristic variables combined with multivariate algorithms to construct data models. The ANN model was the best with accuracy = 0.983, precision = 0.984, and external verification showed the reliability and practicability of ANN model. CONCLUSION: ANN model combined with MS data is of great significance for tdigital identification of AR, VR, and IR. It is an important reference for developing the digital identification of traditional Chinese medicines at the individual level based on UHPLC-QTOF-MS and multivariate algorithms.

15.
Diabetes Obes Metab ; 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38874096

RESUMO

AIM: To analyse the association between serum bile acid (BA) profile and heart failure (HF) with preserved ejection fraction (HFpEF) in patients with metabolic dysfunction-associated fatty liver disease (MAFLD). METHODS: We enrolled 163 individuals with biopsy-proven MAFLD undergoing transthoracic echocardiography for any indication. HFpEF was defined as left ventricular ejection fraction >50% with at least one echocardiographic feature of HF (left ventricular diastolic dysfunction, abnormal left atrial size) and at least one HF sign or symptom. Serum levels of 38 BAs were analysed using ultra-performance liquid chromatography coupled with tandem mass spectrometry. RESULTS: Among the 163 patients enrolled (mean age 47.0 ± 12.8 years, 39.3% female), 52 (31.9%) and 43 (26.4%) met the HFpEF and pre-HFpEF criteria, and 38 serum BAs were detected. Serum ursodeoxycholic acid (UDCA) and hyocholic acid (HCA) species were lower in patients with HFpEF and achieved statistical significance after correction for multiple comparisons. Furthermore, decreases in glycoursodeoxycholic acid and tauroursodeoxycholic acid were associated with HF status. CONCLUSIONS: In this exploratory study, specific UDCA and HCA species were associated with HFpEF status in adults with biopsy-confirmed MAFLD.

16.
Artigo em Inglês | MEDLINE | ID: mdl-38908982

RESUMO

The prognosis of patients with decompensated cirrhosis is poor, with significantly increased liver-related mortality rates. With the rising tide of decompensated cirrhosis associated with metabolic dysfunction-associated steatotic liver disease (MASLD), the role of metabolic bariatric surgery (MBS) in achieving hepatic recompensation is garnering increasing attention. However, the complexity of preoperative assessment, the risk of postoperative disease recurrence, and the potential for patients to experience surgical complications of the MBS present challenges. In this opinion article we analyze the potential of MBS to induce recompensation in MASLD-related cirrhosis, discuss the mechanisms by which MBS may affect recompensation, and compare the characteristics of different MBS procedures; we highlight the therapeutic potential of MBS in MASLD-related cirrhosis recompensation and advocate for research in this complex area.

17.
Colloids Surf B Biointerfaces ; 240: 113998, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38823340

RESUMO

Photoactivated therapy has gradually emerged as a promising and rapid method for combating bacteria, aimed at overcoming the emergence of drug-resistant strains resulting from the inappropriate use of antibiotics and the subsequent health risks. In this work, we report the facile fabrication of Zn3[Fe(CN)6]/g-C3N4 nanocomposites (denoted as ZHF/g-C3N4) through the in-situ loading of zinc hexacyanoferrate nanospheres onto two-dimensional g-C3N4 sheets using a simple metal-organic frameworks construction method. The ZHF/g-C3N4 nanocomposite exhibits enhanced antibacterial activity through the synergistic combination of the excellent photothermal properties of ZHF and the photodynamic capabilities of g-C3N4. Under dual-light irradiation (420 nm + 808 nm NIR), the nanocomposites achieve remarkable bactericidal efficacy, eliminating 99.98% of Escherichia coli and 99.87% of Staphylococcus aureus within 10 minutes. Furthermore, in vivo animal experiments have demonstrated the outstanding capacity of the composite in promoting infected wound healing, achieving a remarkable wound closure rate of 99.22% after a 10-day treatment period. This study emphasizes the potential of the ZHF/g-C3N4 nanocomposite in effective antimicrobial applications, expanding the scope of synergistic photothermal/photodynamic therapy strategies.


Assuntos
Antibacterianos , Escherichia coli , Nanocompostos , Staphylococcus aureus , Cicatrização , Nanocompostos/química , Cicatrização/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Antibacterianos/farmacologia , Antibacterianos/química , Animais , Fotoquimioterapia , Testes de Sensibilidade Microbiana , Camundongos , Esterilização/métodos , Ferrocianetos/química , Ferrocianetos/farmacologia , Tamanho da Partícula , Zinco/química , Zinco/farmacologia , Terapia Fototérmica , Propriedades de Superfície , Compostos de Nitrogênio/química , Compostos de Nitrogênio/farmacologia , Grafite
18.
Cancers (Basel) ; 16(11)2024 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-38893153

RESUMO

Numerous studies have reported that Dyrk1A, Dyrk1B, and Clk1 are overexpressed in multiple cancers, suggesting a role in malignant disease. Here, we introduce a novel class of group-selective kinase inhibitors targeting Dyrk1A, Dyrk1B, and Clk1. This was achieved by modifying our earlier selective Clk1 inhibitors, which were based on the 5-methoxybenzothiophene-2-carboxamide scaffold. By incorporating a 5-hydroxy group, we increased the potential for additional hydrogen bond interactions that broadened the inhibitory effect to include Dyrk1A and Dyrk1B kinases. Within this series, compounds 12 and 17 emerged as the most potent multi-kinase inhibitors against Dyrk1A, Dyrk1B, and Clk1. Furthermore, when assessed against the most closely related kinases also implicated in cancer, the frontrunner compounds revealed additional inhibitory activity against Haspin and Clk2. Compounds 12 and 17 displayed high potency across various cancer cell lines with minimal effect on non-tumor cells. By examining the effect of these inhibitors on cell cycle distribution, compound 17 retained cells in the G2/M phase and induced apoptosis. Compounds 12 and 17 could also increase levels of cleaved caspase-3 and Bax, while decreasing the expression of the antiapoptotic Bcl-2 protein. These findings support the further study and development of these compounds as novel anticancer therapeutics.

19.
Fitoterapia ; 177: 106057, 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38844141

RESUMO

The pericarps of Zanthoxylum schinifolium Sieb. et Zucc were called "green huajiao", which were used as traditional folk medicine and popular seasoning in China. In this study, twenty-seven alkylamides, including a rare alkylamide containing two amide groups (1), an alkylamide with a furan ring (5), six new alkylamide analogues (2-4, 6-8), together with nineteen known alkylamides (9-27) were isolated from green huajiao. Their structures were elucidated by extensive spectroscopic analysis, including 1D, 2D NMR, HRESIMS, and UV spectra. Furthermore, compounds 5, 18, 21, and 22 exhibited weak protective activity for corticosterone-induced PC12 cells damage.

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