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1.
ACS Omega ; 9(26): 28648-28658, 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38973936

RESUMO

Basalt is a suitable target area for CO2 storage. Clarifying the evolution of the pore structure during CO2-fluid-basalt interactions is a crucial element in the preparation of a CO2 geologic storage operation. In this study, a pore-scale phase field model is proposed to simulate the CO2-fluid-basalt interaction process of Snake River Plain basalt. Our model is suitable for complex multimineral natural rocks, and the initial mineral distribution before the reaction can be completely based on a real 3D rock image without the need to simplify the mineral geometry. The simulation results demonstrate that after 120 days of dissolution-precipitation reaction, the volume of secondary minerals (3.75%) exceeds that of dissolved minerals (2.01%), leading to a reduction in porosity by 1.74%. The pore structure of the basalt changes significantly, and the connectivity is obviously reduced. The effects of temperature and pressure on the reaction rate were examined to guide site selection for CO2 sequestration. The results show that increasing temperature and pressure can accelerate the reaction rate, but the impact of pressure on the reaction rate is negligible compared to the significant influence of temperature. Therefore, an area with a high geothermal gradient is conducive to geological sequestration.

2.
J Ethnopharmacol ; 334: 118513, 2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-38969151

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: 2,3,5,4'-tetrahydroxy-stilbene-2-O-ß-D-glucoside (TSG) is the principal bioactive compound contained in Polygonum multiflorum Thunb. (PMT), which is traditionally recorded to possess tonic and anti-aging efficacy. AIM OF THE STUDY: To identify the TSG-provided promotion on liver regeneration (LR) following partial hepatectomy (PHx) in mice and to explicate its involved mechanism. MATERIALS AND METHODS: The promotion of TSG on LR was evaluated by hematoxylin and eosin (H&E), 5-bromodeoxyuridinc (BrdU) and Ki-67 staining, and measuring the level of proliferating cell nuclear antigen (PCNA) and Cyclin D1 in mice with PHx at different time points. Gene Expression Omnibus (GEO, GSE15239) database and the label-free quantitative proteomics from liver of mice at 24 h after PHx were integrated to identify potential involved critical proteins, which were verified by Western-blot, Real-time polymerase chain reaction (RT-PCR), molecular docking and luciferase activity assay. Primary hepatocytes isolated from mice were used to investigate the TSG-provided promotion on proliferation in vitro. RESULTS: TSG (20 mg/kg) promoted LR in mice after PHx. Results from RNA expression data from clinical samples and proteomic analysis from liver tissues indicated that peroxisome proliferator-activated receptor α (PPARα)-mediated fatty acid metabolism pathway were crucially associated with the TSG-provided promotion on LR. TSG enhanced the nuclear translocation of PPARα and the mRNA expression of a series of PPARα-regulated downstream genes. In addition, TSG lowered hepatic triglyceride (TG) and non-esterified fatty acid (NEFA) amounts and increased hepatic adenosine triphosphate (ATP) level in mice after PHx. TSG up-regulated the transcriptional activity of PPARα in vitro. Next results displayed that TSG promoted cell proliferation as well as ATP level in mice primary hepatocytes, which were abolished when PPARα was suppressed. Meanwhile, the cell viability was also elevated in mice primary hepatocytes treated with ATP. CONCLUSION: Activating PPARα-mediated fatty acid ß-oxidation (FAO) pathway led to the production of ATP, which contributed to the TSG-provided promotion on LR after PHx in mice.

3.
Biosci Rep ; 44(7)2024 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-38868980

RESUMO

Sulforaphane (SFN) has shown diverse effects on human health and diseases. SFN was administered daily to C57BL/6J mice at doses of 1 mg/kg (SFN1) and 3 mg/kg (SFN3) for 8 weeks. Both doses of SFN accelerated body weight increment. The cross-sectional area and diameter of Longissimus dorsi (LD) muscle fibers were enlarged in SFN3 group. Triglyceride (TG) and total cholesterol (TC) levels in LD muscle were decreased in SFN groups. RNA sequencing results revealed that 2455 and 2318 differentially expressed genes (DEGs) were found in SFN1 and SFN3 groups, respectively. Based on GO enrichment analysis, 754 and 911 enriched GO terms in the SFN1 and SFN3 groups, respectively. KEGG enrichment analysis shown that one KEGG pathway was enriched in the SFN1 group, while six KEGG pathways were enriched in the SFN3 group. The expressions of nine selected DEGs validated with qRT-PCR were in line with the RNA sequencing data. Furthermore, SFN treatment influenced lipid and protein metabolism related pathways including AMPK signaling, fatty acid metabolism signaling, cholesterol metabolism signalling, PPAR signaling, peroxisome signaling, TGFß signaling, and mTOR signaling. In summary, SFN elevated muscle fibers size and reduced TG and TC content of in LD muscle by modulating protein and lipid metabolism-related signaling pathways.


Assuntos
Isotiocianatos , Metabolismo dos Lipídeos , Camundongos Endogâmicos C57BL , Músculo Esquelético , Transdução de Sinais , Sulfóxidos , Animais , Isotiocianatos/farmacologia , Sulfóxidos/farmacologia , Transdução de Sinais/efeitos dos fármacos , Músculo Esquelético/metabolismo , Músculo Esquelético/efeitos dos fármacos , Masculino , Metabolismo dos Lipídeos/efeitos dos fármacos , Camundongos , Colesterol/metabolismo , Triglicerídeos/metabolismo , Desenvolvimento Muscular/efeitos dos fármacos , Oxirredução/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos
4.
Front Nutr ; 11: 1408618, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38840702

RESUMO

Introduction: The incorporation of Staphylococcus xylosus in sausage production is hypothesized to affect various physicochemical properties and flavor profiles of sausages. This study aimed to evaluate the simulation of these features in a sausage model and establish its applicability for in vitro studies. Methods: Both a control and an experimental model, inclusive of Staphylococcus xylosus, were assessed for changes in physicochemical indexes (pH and water activity, Aw) and the concentration of flavoring components (esters and aldehydes). Thiobarbituric acid reactive substances (TBARS) values were also measured to evaluate lipid oxidation. Results: The introduction of Staphylococcus xylosus resulted in no significant changes in pH and Aw between the sausage and the model. However, there was a considerable increase in the content of volatile flavor compounds, specifically esters and aldehydes, in the experimental groups compared to the control. Additionally, the TBARS values in experimental groups were significantly lower than those in the control group at the end of the testing period. Discussion: The findings indicate that Staphylococcus xylosus plays a critical role in enhancing the flavor profile of sausages through the increased synthesis of volatile compounds and inhibiting fat oxidation. The sausage model effectively simulated the physicochemical and flavor index responses, demonstrating its potential utility for further in vitro research on sausage fermentation and preservation techniques.

5.
Acta Biomater ; 182: 199-212, 2024 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-38734283

RESUMO

Reducing plaque lipid content and enhancing plaque stability without causing extensive apoptosis of foam cells are ideal requirements for developing a safe and effective treatment of atherosclerosis. In this study, we synthesized IR780-Gd-OPN nanomicelles by conjugating osteopontin (OPN) and loading a gadolinium-macrocyclic ligand (Gd-DOTA) onto near-infrared dye IR780-polyethylene glycol polymer. The nanomicelles were employed for mild phototherapy of atherosclerotic plaques and dual-mode imaging with near-infrared fluorescence and magnetic resonance. In vitro results reveal that the mild phototherapy mediated by IR780-Gd-OPN nanomicelles not only activates heat shock protein (HSP) 27 to protect foam cells against apoptosis but also inhibits the nuclear factor kappa-B (NF-κB) pathway to regulate lipid metabolism and macrophage polarization, thereby diminishing the inflammatory response. In vivo results further validate that mild phototherapy effectively reduces plaque lipid content and size while simultaneously enhancing plaque stability by regulating the ratio of M1 and M2-type macrophages. In summary, this study presents a promising approach for developing a safe and highly efficient method for the precise therapeutic visualization of atherosclerosis. STATEMENT OF SIGNIFICANCE: The rupture of unstable atherosclerotic plaques is a major cause of high mortality rates in cardiovascular diseases. Therefore, the ideal outcome of atherosclerosis treatment is to reduce plaque size while enhancing plaque stability. To address this challenge, we designed IR780-Gd-OPN nanomicelles for mild phototherapy of atherosclerosis. This treatment can effectively reduce plaque size while significantly improving plaque stability by increasing collagen fiber content and elevating the ratio of M2/M1 macrophages, which is mainly attributed to the inhibition of the NF-κB signaling pathway by mild phototherapy-activated HSP27. In summary, our proposed mild phototherapy strategy provides a promising approach for safe and effective treatment of atherosclerosis.


Assuntos
Micelas , NF-kappa B , Fototerapia , Placa Aterosclerótica , Placa Aterosclerótica/patologia , Animais , NF-kappa B/metabolismo , Camundongos , Indóis/química , Indóis/farmacologia , Masculino , Gadolínio/química , Gadolínio/farmacologia , Células RAW 264.7 , Transdução de Sinais/efeitos dos fármacos , Nanopartículas/química , Camundongos Endogâmicos C57BL , Progressão da Doença , Humanos
6.
Br J Haematol ; 204(6): 2157-2158, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38699807

RESUMO

Primary immune thrombocytopenia (ITP) is an acquired autoimmune disease with multiple immune cells take part in the pathogenesis. Macrophages play multiple roles in both innate and adaptive immune system. The report by Jiani Mo and colleagues identified new biomarkers and explore the role of mitophagy and ferroptosis in ITP pathogenesis. Commentary on: Mo et al. Comprehensive analysis and prediction model of mitophagy and ferroptosis in primary immune thrombocytopenia. Br J Haematol 2024;204:2429-2442.


Assuntos
Macrófagos , Púrpura Trombocitopênica Idiopática , Humanos , Macrófagos/imunologia , Macrófagos/metabolismo , Púrpura Trombocitopênica Idiopática/imunologia , Púrpura Trombocitopênica Idiopática/patologia , Biomarcadores , Mitofagia , Ferroptose
7.
Free Radic Biol Med ; 222: 27-40, 2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38815774

RESUMO

Liver fibrosis is a key and reversible stage in the progression of many chronic liver diseases to cirrhosis or hepatocellular carcinoma. Forsythiaside-A (FTA), a main compound isolated from Forsythiae Fructus, has an excellent liver protective activity. This study aims to investigate the efficacy of FTA in improving cholestatic liver fibrosis. Bile-duct-ligation (BDL) was conducted to induce liver fibrosis in mice. Hepatic collagen deposition was evaluated by Masson and Sirus red staining. The bile acid spectrum in the liver and serum was analyzed by mass spectrometry. Liver oxidative stress injury and mitochondria damage were observed by using Mito-Tracker Red fluorescence staining, transmission electron microscopy, etc. The level of ferrous iron (Fe2+) and the expression of ferroptosis-associated molecules were detected. The binding between FTA and its target protein was confirmed by Co-immunoprecipitation (Co-IP), cellular thermal shift assay (CETSA), drug affinity responsive target stability (DARTS) and surface plasmon resonance (SPR). Our results demonstrated that FTA alleviated BDL-induced liver fibrosis in mice. FTA did not decrease the elevated amount of bile acids in BDL-treated mice, but reduced the bile acid-induced mitochondrial damage, oxidative stress and ferroptosis in hepatocytes, and also induced nuclear factor erythroid 2-related factor-2 (Nrf2) activation. In Nrf2 knock-out mice, the FTA-provided protection against BDL-induced liver fibrosis was disappeared, and FTA's inhibition on mitochondrial damage, oxidative stress and ferroptosis were lowered. Further results displayed that FTA could directly bind to Kelch-like ECH-associated protein-1 (Keap1), thereby activating Nrf2. Moreover, the BDL-induced liver fibrosis was markedly weakened in liver-specific Keap1 knockout mice. Hence, this study suggests that FTA alleviated the BDL-induced liver fibrosis through attenuating mitochondrial damage and ferroptosis in hepatocytes by activating Nrf2 via directly binding to Keap1.

8.
BMC Surg ; 24(1): 123, 2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38658911

RESUMO

OBJECTIVE: This study introduced the modified Q-type purse-string suture duodenal stump embedding method, a convenient way to strengthen the duodenum, and compared it to the conventional one to assess its efficacy and safety. METHODS: This retrospective analysis examined 612 patients who received laparoscopic gastrectomy for gastric Cancer at a single center. The patients were divided into Not Reinforced Group (n = 205) and Reinforced Group (n = 407) according to the surgical approach to the duodenal stump. The reinforced group was further divided into a modified Q-type purse-string suture embedding method group (QM, n = 232) and a conventional suture duodenal stump embedding method group (CM, n = 175) according to the methods of duodenal stump enhancement. Clinicopathological characteristics, operative variables, and short-term complications were documented and analyzed. RESULTS: The incidence of duodenal stump leakage(DSL) in the Not Reinforced Group was higher compared to the Reinforced Group, although the difference was not statistically significant [2.4% (5/205) vs 0.7% (3/407), p = 0.339]. Additionally, the Not Reinforced Group exhibited a higher rate of Reoperation due to DSL compared to the Reinforced Group [2 (1.0%) vs. 0, p = 0.046], with one patient in the Not Reinforced Group experiencing mortality due to DSL [1 (0.5%) vs 0, p = 0.158]. Subgroup analysis within the Reinforced Group revealed that the modified Q-type purse-string suture embedding group (QM) subgroup demonstrated statistically significant advantages over the conventional suture embedding group (CM) subgroup. QM exhibited shorter purse-string closure times (4.11 ± 1.840 vs. 6.05 ± 1.577, p = 0.001), higher purse-string closure success rates (93.1% vs. 77.7%, p = 0.001), and greater satisfaction with purse-string closure [224 (96.6%) vs 157 (89.7%), p = 0.005]. No occurrences of duodenal stump leakage were observed in the QM subgroup, while the CM subgroup experienced two cases [2 (1.1%)], though the difference was not statistically significant. Both groups did not exhibit statistically significant differences in secondary surgery or mortality related to duodenal stump leakage. CONCLUSION: Duodenal Stump Leakage (DSL) is a severe but low-incidence complication. There is no statistically significant relationship between the reinforcement of the duodenal stump and the incidence of DSL. However, laparoscopic reinforcement of the duodenal stump can reduce the severity of fistulas and the probability of Reoperation. The laparoscopic Q-type purse-string suture duodenal stump embedding method is a simple and effective technique that can, to some extent, shorten the operation time and enhance satisfaction with purse-string closure. There is a trend towards reducing the incidence of DSL, thereby improving patient prognosis to a certain extent.


Assuntos
Duodeno , Gastrectomia , Laparoscopia , Neoplasias Gástricas , Técnicas de Sutura , Humanos , Gastrectomia/métodos , Laparoscopia/métodos , Neoplasias Gástricas/cirurgia , Feminino , Estudos Retrospectivos , Masculino , Pessoa de Meia-Idade , Idoso , Duodeno/cirurgia , Resultado do Tratamento , Adulto , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia
9.
Ann Hematol ; 103(7): 2245-2256, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38644415

RESUMO

BACKGROUND: Aplastic anemia (AA) is a kind of bone marrow failure (BMF) characterized by pancytopenia with hypoplasia/aplasia of bone marrow. Immunosuppressive therapy and bone marrow transplantation are effective methods to treat severe aplastic anemia. However, the efficacy is limited by complications and the availability of suitable donors. This study aimed to determine whether any circulating druggable protein levels may have causal effects on AA and provide potential novel drug targets for AA. METHODS: Genetic variants strongly associated with circulating druggable protein levels to perform Mendelian randomization (MR) analyses were used. The effect of these druggable protein levels on AA risk was measured using the summary statistics from a large-scale proteomic genome-wide association study (GWAS) and FinnGen database ( https://www.finngen.fi/en/access_results ). Multivariable MR analyses were performed to statistically adjust for potential confounders, including platelet counts, reticulocyte counts, neutrophil counts, and proportions of hematopoietic stem cells. RESULTS: The data showed that higher level of circulating IFN-γ levels was causally associated with AA susceptibility. The causal effects of circulating IFN-γ levels on the AA were broadly consistent, when adjusted for platelet counts, reticulocyte counts, neutrophil counts and proportions of hematopoietic stem cells. CONCLUSIONS: High levels of circulating IFN-γ levels might increase the risk of AA and might provide a potential novel target for AA.


Assuntos
Anemia Aplástica , Estudo de Associação Genômica Ampla , Interferon gama , Análise da Randomização Mendeliana , Proteoma , Anemia Aplástica/genética , Anemia Aplástica/sangue , Humanos , Interferon gama/sangue , Proteoma/análise , Masculino , Feminino
10.
J Robot Surg ; 18(1): 159, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38578352

RESUMO

Currently, there is no consensus on the position and method for temporary ileostomy in robotic-assisted low anterior resection for rectal cancer. Herein, this study introduced the B-type sutured ileostomy, a new temporary ileostomy technique, and compared it to the traditional one to assess its efficacy and safety. Between September 2020 and December 2022 in our centre, B-type sutured ileostomy was performed on 124 patients undergoing robotic-assisted low anterior resection for rectal cancer. A retrospective review of a prospectively collected database identified patients who underwent robotic-assisted low anterior resection for rectal cancer with a temporary ileostomy between January 2018 and December 2022. Patients who underwent B-type sutured ileostomy (B group) were matched in a 1:1 ratio with patients who underwent traditional ileostomy (Control group) using a propensity score based on age, sex, BMI, Comorbidity, American Society of Anesthesiologists (ASA) score, and Prior abdominal surgery history. Surgical and postoperative outcomes, health status, and stoma closure data were analyzed for both groups. ClinicalTrials.gov Identifier:NCT05915052.  The B group (n = 118) shows advantages compared to the Control group (n = 118) regarding total operation time (155.98 ± 21.63 min vs 168.92 ± 21.49 min, p = 0.001), postoperative body pain (81.92 ± 4.12 vs 78.41 ± 3.02, p = 0.001) and operation time of stoma closure (46.19 ± 11.30 min vs 57.88 ± 11.08 min, p = 0.025). The two groups had no other notable differences. The B-type sutured ileostomy is a safe and feasible option in robotic-assisted low anterior resection for rectal cancer. The B-type sutured ileostomy may offer advantages such as shorter overall surgical duration, lighter postoperative pain, and shorter second-stage ostomy incorporation surgery. However, attention should be directed towards the occurrence of stoma prolapse.


Assuntos
Protectomia , Neoplasias Retais , Procedimentos Cirúrgicos Robóticos , Humanos , Ileostomia/métodos , Dor Pós-Operatória , Complicações Pós-Operatórias/epidemiologia , Protectomia/métodos , Pontuação de Propensão , Neoplasias Retais/cirurgia , Estudos Retrospectivos , Procedimentos Cirúrgicos Robóticos/métodos
11.
Phytomedicine ; 128: 155368, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38498951

RESUMO

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a chronic disease characterized by the abnormal proliferation of fibroblast and excessive deposition of extracellular matrix (ECM), accompanied by inflammation and ultimately respiratory failure. Yinhuang granule (YHG), with clinical properties of clearing heat, detoxifying and anti-inflammation, is commonly used to heal upper respiratory diseases in China for decades. PURPOSE: To explore the improvement of YHG on bleomycin (BLM)-induced IPF in mice and its possible engaged mechanism. METHODS: The mortality rate was recorded, lung function was determined and hematoxylin-eosin (H&E) staining was carried out to explore the alleviation of YHG on BLM-caused IPF in mice. Hydroxyproline, collagen I and collagen III contents were detected, and Sirius red and Masson staining were conducted to evaluate YHG's alleviation on lung fibrosis. The underlying mechanism was predicted by network pharmacology, and confirmed by Real-time polymerase chain reaction (RT-PCR), Western-blot (WB) and enzyme linked immunosorbent assay (ELISA). The binding affinity between related key proteins and active compounds in YHG was calculated by using molecular docking, and further validated by cellular thermal shift assay (CESTA). RESULTS: YHG (400, 800 mg/kg) weakened lung damage and pulmonary fibrosis in mice induced by BLM. Network pharmacology and experimental validation displayed that inflammation and angiogenesis participated in the YHG-provided improvement on IPF, and key involved molecules included tumor necrosis factor-α (TNFα), vascular endothelial growth factor-A (VEGFA), interleukine-6 (IL-6), etc. The data of molecular docking presented that some main active compounds from YHG had a high binding affinity with TNFR1 or VEGFR2, and some of them were further validated by CESTA. CONCLUSION: YHG effectively improved the BLM-induced IPF in mice via reducing inflammation and angiogenesis.


Assuntos
Bleomicina , Medicamentos de Ervas Chinesas , Fibrose Pulmonar Idiopática , Simulação de Acoplamento Molecular , Farmacologia em Rede , Fator A de Crescimento do Endotélio Vascular , Animais , Fibrose Pulmonar Idiopática/tratamento farmacológico , Fibrose Pulmonar Idiopática/induzido quimicamente , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/química , Camundongos , Fator A de Crescimento do Endotélio Vascular/metabolismo , Masculino , Fator de Necrose Tumoral alfa/metabolismo , Humanos , Pulmão/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Modelos Animais de Doenças
12.
J Robot Surg ; 18(1): 83, 2024 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-38386188

RESUMO

Intersphincteric resection (ISR) is a viable option for sphincter preservation in early ultra-low rectal cancer, but postoperative anal dysfunction remains a concern. This study evaluates the outcomes of robotic ISR with coloanal anastomosis in early ultra-low rectal cancer, comparing its efficacy and safety with laparoscopic ISR. Retrospective analysis was conducted on data from 74 consecutive patients undergoing robotic intersphincteric resection (R-ISR) for early ultra-low rectal cancer between January 2017 and December 2018 (R-ISR group), matched with 110 patients undergoing laparoscopic intersphincteric resection (L-ISR). After 1:1 propensity score matching, each group comprised 68 patients. Comparative analyses covered surgical outcomes, complications, long-term results, and anal function. The R-ISR group showed longer total operative time than the L-ISR group (211.7 ± 25.3 min vs. 191.2 ± 23.0 min, p = 0.001), but less intraoperative bleeding (55.2 ± 20.7 ml vs. 69.2 ± 22.9 ml, p = 0.01). R-ISR group had fewer conversions to APR surgery (6/8.8% vs. 14/20.6%). Other perioperative indicators were similar. R-ISR exhibited a smaller tumor margin, superior mesorectal integrity, and comparable histopathological outcomes. Postoperative complications, 3-year and 5-year DFS, and OS were similar. At the 1-year follow-up, the Wexner Incontinence Score favored R-ISR (9.24 ± 4.03 vs. 11.06 ± 3.77, p = 0.048). Although R-ISR prolongs the operative time, its surgical safety and oncological outcomes are similar to conventional ISR procedures. Furthermore, it further shortens the margin of anal preservation, reduces the rate of conversion to APR surgery, and improves postoperative anal function.


Assuntos
Laparoscopia , Neoplasias Retais , Procedimentos Cirúrgicos Robóticos , Humanos , Pontuação de Propensão , Estudos Retrospectivos , Procedimentos Cirúrgicos Robóticos/métodos , Neoplasias Retais/cirurgia
13.
Crit Rev Toxicol ; 54(2): 123-133, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38411492

RESUMO

Pyrrolizidine alkaloids (PAs) are one type of phytotoxins distributed in various plants, including many medicinal herbs. Many organs might suffer injuries from the intake of PAs, and the liver is the most susceptible one. The diagnosis, toxicological mechanism, and detoxification of PAs-induced hepatotoxicity have been studied for several decades, which is of great significance for its prevention, diagnosis, and therapy. When the liver was exposed to PAs, liver sinusoidal endothelial cells (LSECs) loss, hemorrhage, liver parenchymal cells death, nodular regeneration, Kupffer cells activation, and fibrogenesis occurred. These pathological changes classified the PAs-induced liver injury as acute, sub-acute, and chronic type. PAs metabolic activation, mitochondria injury, glutathione (GSH) depletion, inflammation, and LSECs damage-induced activation of the coagulation system were well recognized to play critical roles in the pathological process of PAs-induced hepatotoxicity. A lot of natural compounds like glycyrrhizic acid, (-)-epicatechin, quercetin, baicalein, chlorogenic acid, and so on were demonstrated to be effective in alleviating PAs-induced liver injury, which rendered them huge potential to be developed into therapeutic drugs for PAs poisoning in clinics. This review presents updated information about the diagnosis, toxicological mechanism, and detoxification studies on PAs-induced hepatotoxicity.


Assuntos
Doença Hepática Crônica Induzida por Substâncias e Drogas , Plantas Medicinais , Alcaloides de Pirrolizidina , Alcaloides de Pirrolizidina/toxicidade , Alcaloides de Pirrolizidina/metabolismo , Plantas Medicinais/metabolismo , Células Endoteliais/metabolismo , Células Endoteliais/patologia , Doença Hepática Crônica Induzida por Substâncias e Drogas/patologia , Glutationa/metabolismo , Extratos Vegetais
14.
Foods ; 13(3)2024 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-38338531

RESUMO

Saccharomyces cerevisiae (S. cerevisiae) and Kluyveromyces marxianus (K. marxianus) are often used as fermenters in yogurt and alcohol, and have been less studied within meat products. The yeasts were added to sauce meat, and the uninoculated group served as a control in this study to examine and compare the changing patterns of physicochemical and flavor characteristics of S. cerevisiae and K. marxianus on sauce meat during storage. The changes in moisture content, aw, pH, thiobarbituric acid reactive substances (TBARS), and other flavor characteristics were measured in sauce meat during the first, second, fourth, and sixth months after production. The following factors were examined: moisture content, aw, pH, TBARS, peroxide value (POV), acid value (AV), soluble protein (SP), free amino acid (FAA), and volatile flavoring compounds. With VIP > 1 and p < 0.05 as the screening conditions, the partial least squares model (PLS-DA) was used to assess the distinctive flavor components in the sausages. The findings demonstrated that the three groups' changes in sauce meat were comparable during the first two months of storage but differed significantly between the 4th and 6th months. The moisture content, water activity, and pH of the sauce meat decreased gradually with the storage time; TBARS, AV, and FAA increased significantly; SP decreased significantly from 2.61 to 1.72, while POV increased to 0.03 and then decreased to 0.02. The POV and TBARS values of the yeast-infected meat were substantially lower than those of the control group, and the POV and TBARS values of the meat inoculated with S. cerevisiae were particularly decreased (p < 0.05). The POV and TBARS values of SC (S. cerevisiae group) decreased by 49.09% and 40.15%, respectively, compared to CK (the control group) at the time of storage until June. The experimental group (KM: K. marxianus group) significantly increased the SP and FAA values of the sauce meat (p < 0.05) by 32.4% and 29.84% compared to the CK group, respectively. Esters and olefins as well as alcohols and esters were much greater in meat that had been supplemented with S. cerevisiae and K. marxianus than in meat from the control group. In conclusion, inoculating sauce meat with S. cerevisiae can significantly enhance the quality and flavor of sauce meat while it is being stored.

15.
J Ethnopharmacol ; 322: 117554, 2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38092318

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Rheumatoid arthritis (RA), a chronic auto-immune disease, will cause serious joint damage and disability. Glycyrrhizae Radix et Rhizoma (GRR) is commonly included in many anti-RA formulas used in the clinical practice in China. AIM OF THE STUDY: To elucidate the alleviation of GRR and its active compounds on RA and the possible engaged mechanism. MATERIALS AND METHODS: The clinical score, paw swelling degree and pain threshold were detected in the collagen-induced arthritis (CIA) in DBA/1 mice. The ankle joints of mice were observed by using X-Ray, hematoxylin-eosin (H&E), masson's trichrome (Masson), and safranin O and fast green (Safranin O) staining. The potential targets of GRR were predicted by network pharmacology and further verified by using enzyme-linked immunosorbent assay (ELISA) and western-blot. Real-time polymerase chain reaction (Real-time PCR) and wound healing assay were conducted in synovial MH7A cells. The interaction between active compounds and potential targets predicted by molecular docking was confirmed by using cellular thermal shift assay (CETSA). RESULTS: GRR (615 mg/kg) obviously alleviated CIA in mice. Network pharmacology implied that GRR might affect angiogenesis and inflammation, among which vascular endothelial growth factor-A (VEGF-A), tumor necrosis factor-α (TNFα), interleukin-1ß (IL-1ß), IL-6 and phosphorylated protein kinase B (AKT) might be the key targets involved in this process. GRR decreased AKT phosphorylation and reduced the elevated levels of TNFα, VEGF-A, IL-1ß and IL-6. Next, in vitro results demonstrated that glycyrrhetinic acid (GA) and isoliquiritigenin (ISL) were two active compounds that inhibited TNFα-induced synovial cell angiogenesis and inflammation. Moreover, GA and ISL actually improved RA in CIA mice. The results of molecular docking and CETSA displayed that ISL and GA might interact with TNF receptor-1 (TNFR1), toll-like receptor-4 (TLR4) and VEGF receptor-2 (VEGFR2), thereby contributing to their inhibition on angiogenesis and inflammation. CONCLUSION: GRR and two active compounds, including ISL and GA, alleviated RA via inhibiting angiogenesis and inflammation.


Assuntos
Artrite Experimental , Artrite Reumatoide , Medicamentos de Ervas Chinesas , Glycyrrhiza , Camundongos , Animais , Artrite Experimental/induzido quimicamente , Artrite Experimental/tratamento farmacológico , Fator A de Crescimento do Endotélio Vascular , Proteínas Proto-Oncogênicas c-akt , Fator de Necrose Tumoral alfa , Interleucina-6 , Simulação de Acoplamento Molecular , Camundongos Endogâmicos DBA , Artrite Reumatoide/patologia , Inflamação
16.
J Affect Disord ; 347: 92-100, 2024 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-37992773

RESUMO

BACKGROUND: Subjective support could ameliorate the adverse effect of (pre)frailty on depressive symptoms. However, there is scarce evidence regarding subjective support-focused intervention in preventing depression among (pre)frail community-dwelling older adults. This study aims to explore the effectiveness of subjective support-focused cognitive behavioral therapy (SS-CBT) in preventing depression among this group of population. METHODS: A total of 100 community-dwelling (pre)frail older adults were recruited from six communities in a Chinese city and were randomized to an 8-week SS-CBT group or a wait-list control group. Depressive symptoms and subjective support were assessed at baseline (T0), and at 8 week (T1), 12 week (T2), 16 week (T3) after randomization. Generalized estimating equation was used to examine the effectiveness of SS-CBT on depressive symptoms and subjective support. Hierarchical linear regression models and Bootstrapping method were used to examine whether subjective support mediated the effectiveness of SS-CBT on depressive symptoms. RESULTS: Participants in SS-CBT group reported significant reduction in depressive symptoms (Wald χ2 = 20.800, p < 0.001) and improvement in subjective support (Wald χ2 = 92.855, p < 0.001) compared to those in wait-list control group. Changes in subjective support mediated the effectiveness of SS-CBT on changes in depressive symptoms. LIMITATIONS: Restricted regions to recruit participants, inclusion of the most motivated participants, lack of diagnosis of depression, potential experimenter bias and contamination, short follow-up period, and lack of an active control group. CONCLUSIONS: The findings support the benefits of SS-CBT in preventing depression among (pre)frail community-dwelling older adults, and provide insight into possible mechanisms.


Assuntos
Terapia Cognitivo-Comportamental , Fragilidade , Humanos , Idoso , Depressão/psicologia , Idoso Fragilizado , Vida Independente , Terapia Cognitivo-Comportamental/métodos
17.
Br J Haematol ; 204(4): 1483-1494, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38031970

RESUMO

Primary immune thrombocytopenia (ITP) is an acquired autoimmune disease. Cellular and systemic lipid metabolism plays a significant role in the regulation of immune cell activities. However, the role of lipoprotein lipids and apolipoproteins in ITP remains elusive. The automatic biochemistry analyser was used to measure the levels of serum total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), apolipoprotein A-I (apoA-I), apoB, apoE and lipoprotein a [LP(a)]. Genetic variants strongly associated with circulating lipoprotein lipids and apolipoproteins (LDL-C, apoB, TG, HDL-C and apoA-I) were extracted to perform Mendelian randomization (MR) analyses. Finally, drug-target MR and passive ITP mice model was used to investigate the potential druggable targets of ITP. Levels of HDL-C, apoA-I, decreased and LP(a) increased in ITP patients compared with healthy controls. Low HDL-C was causally associated with ITP susceptibility. Through drug-target MR and animal modelling, ABCA1 was identified as a potential target to design drugs for ITP. Our study found that lipid metabolism is related to ITP. The causative association between HDL-C and the risk of ITP was also established. The study provided new evidence of the aetiology of ITP. ABCA1 might be a potential drug target for ITP.


Assuntos
Apolipoproteína A-I , Púrpura Trombocitopênica Idiopática , Animais , Camundongos , Humanos , Apolipoproteína A-I/genética , LDL-Colesterol , Lipídeos , Análise da Randomização Mendeliana , Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Púrpura Trombocitopênica Idiopática/genética , Apolipoproteínas/genética , Triglicerídeos , HDL-Colesterol
18.
Electrophoresis ; 45(5-6): 505-516, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38037287

RESUMO

Insertion/deletion polymorphisms (InDels) are a category of highly prevalent markers in the human genome, characterized by their distinctive attributes, including short amplicon sizes and low mutation rates, which have shown great potential in forensic applications. Multi-allelic InDel and multi-InDel markers, collectively abbreviated as MM-InDels, were developed to enhance polymorphism by the introduction of novel alleles. Nevertheless, the relatively low mutation rates of InDels, coupled with the founder effect, result in distinct allele frequency distributions among populations. The divergent characteristics of InDels in different populations also pose challenges to the establishment of universally efficient InDel multiplex assays. To enhance the system efficiency of the InDel assay and its applicability across diverse populations, 39 MM-InDels with high polymorphism in five different ancestry superpopulations were selected from the 1000 Genomes Project dataset and combined with an amelogenin gender marker to construct a multiplex assay (named MMIDplex). The combined power of discrimination and the cumulative probability of exclusion of 39 MM-InDels were 1 - 1.3 × 10-23 and 1 - 9.83 × 10-6 in the Chinese Han population, and larger than 1-10-19 and 1-10-4 in the reference populations, relatively. These results demonstrate that the MMIDplex assay has the potential to obtain sufficient power for individual identification and paternity test in global populations.


Assuntos
Genética Forense , Polimorfismo Genético , Humanos , Genética Forense/métodos , Frequência do Gene/genética , Povo Asiático , Mutação INDEL , Genética Populacional , China
20.
Zhongguo Fei Ai Za Zhi ; 26(10): 765-773, 2023 Oct 20.
Artigo em Chinês | MEDLINE | ID: mdl-37989339

RESUMO

Lung cancer is one of the most common cancers in the world, and its treatment strategy is mainly surgery combined with radiotherapy and chemotherapy. However, long-term chemotherapy will result in drug resistance, which is also one of the difficulties in the treatment of lung cancer. Ferroptosis is an iron-dependent and lipid peroxidation-driven non-apoptotic cell death cascade, occurring when there is an imbalance of redox homeostasis in the cell. Nuclear factor erythroid 2-related factor 2 (Nrf2) is key for cellular antioxidant responses. Numerous studies suggest that Nrf2 assumes an extremely important role in regulation of ferroptosis, for its various functions in iron, lipid, and amino acid metabolism, and so on. In this review, a brief overview of the research progress of ferroptosis over the past decade will be presented. In particular, the mechanism of ferroptosis and the regulation of ferroptosis by Nrf2 will be discussed, as well as the role of the Nrf2 pathway and ferroptosis in tumor drug resistance, which will provide new research directions for the treatment of drug-resistant lung cancer patients.
.


Assuntos
Ferroptose , Neoplasias Pulmonares , Humanos , Fator 2 Relacionado a NF-E2/genética , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Resistencia a Medicamentos Antineoplásicos , Ferro
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