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1.
Animals (Basel) ; 14(13)2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38998099

RESUMO

The study determined the impacts of dietary fermented residues' (FBR) inclusion on growth, nutrient utilization, carcass characteristics, and meat properties in fattening pigs. Seventy-two robust pigs were randomly assigned to two experimental groups (Duroc × Landrace × Yorkshire, thirty-six pigs each). Each group was subjected to a 52-day trial, during which they received either a corn-soybean meal-based diet or diet enhanced with a 10% addition of FBR. Consequently, adding 10% FBR caused a significant decrease in the digestive utilization of crude dietary components in fattening pigs (p < 0.05) but showed no significant impact on the growth performance. Additionally, FBR inclusion increased the marbling scores (p < 0.05) and total antioxidant functions (p < 0.05) of muscle tissues, indicating improved meat quality. Gender affected backfat depth, with barrows showing thicker backfat depth. In conclusion, dietary supplementation with 10% FBR in finishing pigs influenced the meat quality by improving the marbling score and antioxidant performance while reducing digestibility without compromising growth performance.

2.
Chemistry ; : e202402119, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-39007706

RESUMO

The lone pair electrons in the electronic structure of molecules have been a prominent research focus in chemistry for more than a century. Stable s2lone pair electrons significantly influence material properties, including thermoelectric properties, nonlinear optical properties, ferroelectricity, and electro(photo)catalysis.While major advances have been achieved in understanding the influence of lone pair electrons on material characteristics, research on this effect in organic-inorganic hybrid materials is in its initial stage. In this work, we successfully obtained a novel organic-inorganic hybrid material incorporating Ge with 4s2 lone pair electrons, (MeHDabco)2[GeBr3]4-H2O (MeHDabco = N-methyl-1,4-diazabicyclo[2.2.2]octane) (1). Driven by the stereochemically active lone pair electrons on the Ge2+, 1 crystallizes in the noncentrosymmetric space group P21 at room temperature and exhibits good second harmonic generation (SHG) responses. Interestingly, 1 also shows electrocatalytic activity for the hydrogen evolution reaction due to the existence of lone pair electrons on Ge2+ cations. The electrochemical experiment combined with the DFT calculations revealed the lone pair electrons act as both an active site for proton adsorption and facilitate the ionization of water. This work not only emphasizes the important role of lone pair electrons in material properties and functions but also provides new insight for designing novel Ge-based hybrid materials.

3.
Front Endocrinol (Lausanne) ; 15: 1404697, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38982993

RESUMO

Adipose tissue, an indispensable organ, fulfils the pivotal role of energy storage and metabolism and is instrumental in maintaining the dynamic equilibrium of energy and health of the organism. Adipocyte hypertrophy and adipocyte hyperplasia (adipogenesis) are the two primary mechanisms of fat deposition. Mature adipocytes are obtained by differentiating mesenchymal stem cells into preadipocytes and redifferentiation. However, the mechanisms orchestrating adipogenesis remain unclear. Autophagy, an alternative cell death pathway that sustains intracellular energy homeostasis through the degradation of cellular components, is implicated in regulating adipogenesis. Furthermore, adipose tissue functions as an endocrine organ, producing various cytokines, and certain inflammatory factors, in turn, modulate autophagy and adipogenesis. Additionally, autophagy influences intracellular redox homeostasis by regulating reactive oxygen species, which play pivotal roles in adipogenesis. There is a growing interest in exploring the involvement of autophagy, inflammation, and oxidative stress in adipogenesis. The present manuscript reviews the impact of autophagy, oxidative stress, and inflammation on the regulation of adipogenesis and, for the first time, discusses their interactions during adipogenesis. An integrated analysis of the role of autophagy, inflammation and oxidative stress will contribute to elucidating the mechanisms of adipogenesis and expediting the exploration of molecular targets for treating obesity-related metabolic disorders.


Assuntos
Adipogenia , Autofagia , Inflamação , Estresse Oxidativo , Adipogenia/fisiologia , Humanos , Autofagia/fisiologia , Estresse Oxidativo/fisiologia , Inflamação/metabolismo , Inflamação/patologia , Animais , Adipócitos/metabolismo , Adipócitos/patologia , Obesidade/metabolismo , Obesidade/patologia , Tecido Adiposo/metabolismo , Tecido Adiposo/patologia
4.
Bioresour Technol ; 406: 131031, 2024 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-38925402

RESUMO

The sustainable management of agricultural waste is essential for curtailing environmental contamination. To address the shortcomings of single treatment methods, this study evaluated the feasibility of combining membrane-covered composting (MC) with vermicomposting. Based on this, the integrated effects of different biochar addition strategies on the combined process were investigated. The aim was to improve the efficiency of vermicomposting while eliminating the negative effects of biochar on earthworms. Addition of biochar before membrane-covered composting increased total earthworm biomass by 25.6 - 31.4 % and reproduction rate by 13.4 - 23.9 %. Specifically, the electrical conductivity (EC) (1061.0 - 1112.0 uS/cm) of the vermicompost was significantly reduced, while the total nutrient content (42.3 - 42.6 mg/g) and germination index (GI) (103.9 - 108.4 %) were maximized. Additionally, reductions in the carbon-to-nitrogen ratio and volatile content were observed. Overall, combination process is a promising approach to improve the quality of vermicomposting. The study's results offer a novel perspective on the value-added treatment of agricultural waste.

5.
Curr Med Sci ; 2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38926331

RESUMO

OBJECTIVE: Bladder outlet obstruction (BOO) results in significant fibrosis in the chronic stage and elevated bladder pressure. Piezo1 is a type of mechanosensitive (MS) channel that directly responds to mechanical stimuli. To identify new targets for intervention in the treatment of BOO-induced fibrosis, this study investigated the impact of high hydrostatic pressure (HHP) on Piezo1 activity and the progression of bladder fibrosis. METHODS: Immunofluorescence staining was conducted to assess the protein abundance of Piezo1 in fibroblasts from obstructed rat bladders. Bladder fibroblasts were cultured under normal atmospheric conditions (0 cmH2O) or exposed to HHP (50 cmH2O or 100 cmH2O). Agonists or inhibitors of Piezo1, YAP1, and ROCK1 were used to determine the underlying mechanism. RESULTS: The Piezo1 protein levels in fibroblasts from the obstructed bladder exhibited an elevation compared to the control group. HHP significantly promoted the expression of various pro-fibrotic factors and induced proliferation of fibroblasts. Additionally, the protein expression levels of Piezo1, YAP1, ROCK1 were elevated, and calcium influx was increased as the pressure increased. These effects were attenuated by the Piezo1 inhibitor Dooku1. The Piezo1 activator Yoda1 induced the expression of pro-fibrotic factors and the proliferation of fibroblasts, and elevated the protein levels of YAP1 and ROCK1 under normal atmospheric conditions in vitro. However, these effects could be partially inhibited by YAP1 or ROCK inhibitors. CONCLUSION: The study suggests that HHP may exacerbate bladder fibrosis through activating Piezo1.

6.
Sci Total Environ ; 946: 174147, 2024 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-38909800

RESUMO

Environmental behaviors of heavy metal in soil are strongly influenced by seasonal freeze-thaw events at the mid-high altitudes. However, the potential impact mechanisms of freeze-thaw cycles on the vertical migration of heavy metal are still poor understood. This study aimed to explore how exogenous cadmium (Cd) migrated and remained in soil during the in-situ seasonal freeze-thaw action using rare earth elements (REEs) as tracers. As a comparison, soil which was incubated in the controlled laboratory (25 °C) was employed. Although there was no statistically significant difference in the Cd levels of different soil depths under different treatments, the original aggregate sources of Cd in the 5-10 cm and 10-15 cm soil layers differed. From the distributions of REEs in soil profile, it can be known that Cd in the subsurface of field incubated soil was mainly from the breakdown of >0.50 mm aggregates, while it was mainly from the <0.106 mm aggregates for the laboratory incubated soil. Furthermore, the dissolved and colloidal Cd concentrations were 0.47 µg L-1 and 0.62 µg L-1 in the leachates from field incubated soil than those from control soil (0.21 µg L-1 and 0.43 µg L-1). Additionally, the colloid-associated Cd in the leachate under field condition was mainly from the breakdown of >0.25 mm aggregates and the direct migration of <0.106 mm aggregates, while it was the breakdown of >0.50 mm and the direct migration of <0.106 mm aggregates for the soil under laboratory condition. Our results for the first time provided insights into the fate of exogenous contaminants in seasonal frozen regions using the rare earth element tracing method.

7.
Int J Biol Sci ; 20(8): 3061-3075, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38904010

RESUMO

Renal fibrosis is the common pathway in the progression of chronic kidney disease (CKD). Acyloxyacyl hydrolase (AOAH) is expressed in various phagocytes and is highly expressed in proximal tubular epithelial cells (PTECs). Research shows that AOAH plays a critical role in infections and chronic inflammatory diseases, although its role in kidney injury is unknown. Here, we found that AOAH deletion led to exacerbated kidney injury and fibrosis after folic acid (FA) administration, which was reversed by overexpression of Aoah in kidneys. ScRNA-seq revealed that Aoah-/- mice exhibited increased subpopulation of CD74+ PTECs, though the percentage of total PTECs were decreased compared to WT mice after FA treatment. Additionally, exacerbated kidney injury and fibrosis seen in Aoah-/- mice was attenuated via administration of methyl ester of (S, R)-3-(4-hydroxyphenyl)-4,5-dihydro-5-isoxazole acetic acid (ISO-1), an inhibitor of macrophage inhibition factor (MIF) and CD74 binding. Finally, AOAH expression was found positively correlated with estimated glomerular filtration rate while negatively correlated with the degree of renal fibrosis in kidneys of CKD patients. Thus, our work indicates that AOAH protects against kidney injury and fibrosis by inhibiting renal tubular epithelial cells CD74 signaling pathways. Targeting kidney AOAH represents a promising strategy to prevent renal fibrosis progression.


Assuntos
Hidrolases de Éster Carboxílico , Macrófagos , Animais , Camundongos , Macrófagos/metabolismo , Hidrolases de Éster Carboxílico/metabolismo , Hidrolases de Éster Carboxílico/genética , Humanos , Antígenos de Diferenciação de Linfócitos B/metabolismo , Antígenos de Diferenciação de Linfócitos B/genética , Insuficiência Renal Crônica/metabolismo , Camundongos Endogâmicos C57BL , Masculino , Antígenos de Histocompatibilidade Classe II/metabolismo , Ácido Fólico/metabolismo , Túbulos Renais/metabolismo , Túbulos Renais/patologia , Fibrose/metabolismo , Camundongos Knockout , Células Epiteliais/metabolismo
8.
Biomed Pharmacother ; 177: 117012, 2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38906025

RESUMO

Myocardial fibrosis is a pathological, physiological change that results from alterations, such as inflammation and metabolic dysfunction, after myocardial infarction (MI). Excessive fibrosis can cause cardiac dysfunction, ventricular remodeling, and heart failure. Caffeic acid (CA), a natural polyphenolic acid in various foods, has cardioprotective effects. This study aimed to explore whether CA exerts a cardioprotective effect to inhibit myocardial fibrosis post-MI and elucidate the underlying mechanisms. Histological observations indicated that CA ameliorated ventricular remodeling induced by left anterior descending coronary artery ligation in MI mice and partially restored cardiac function. CA selectively targeted transforming growth factor-ß receptor 1 (TGFBR1) and inhibited TGFBR1-Smad2/3 signaling, reducing collagen deposition in the infarcted area of MI mice hearts. Furthermore, cell counting (CCK-8) assay, 5-ethynyl-2'-deoxyuridine assay, and western blotting revealed that CA dose-dependently decreased the proliferation, collagen synthesis, and activation of the TGFBR1-Smad2/3 pathway in primary cardiac fibroblasts (CFs) stimulated by TGF-ß1 in vitro. Notably, TGFBR1 overexpression in CFs partially counteracted the inhibitory effects of CA. These findings suggest that CA effectively mitigates myocardial fibrosis and enhances cardiac function following MI and that this effect may be associated with the direct targeting of TGFBR1 by CA.

9.
Math Biosci Eng ; 21(4): 5164-5180, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38872531

RESUMO

B-cell acute lymphoblastic leukemia (B-ALL) is a malignant blood disorder, particularly detrimental to children and adolescents, with recurrent or unresponsive cases contributing significantly to cancer-associated fatalities. IKBKE, associated with innate immunity, tumor promotion, and drug resistance, remains poorly understood in the context of B-ALL. Thus, this research aimed to explore the impact of the IKBKE inhibitor MCCK1 on B-ALL cells. The study encompassed diverse experiments, including clinical samples, in vitro and in vivo investigations. Quantitative real-time fluorescence PCR and protein blotting revealed heightened IKBKE mRNA and protein expression in B-ALL patients. Subsequent in vitro experiments with B-ALL cell lines demonstrated that MCCK1 treatment resulted in reduced cell viability and survival rates, with flow cytometry indicating cell cycle arrest. In vivo experiments using B-ALL mouse tumor models substantiated MCCK1's efficacy in impeding tumor proliferation. These findings collectively suggest that IKBKE, found to be elevated in B-ALL patients, may serve as a promising drug target, with MCCK1 demonstrating potential for inducing apoptosis in B-ALL cells both in vitro and in vivo.


Assuntos
Apoptose , Proliferação de Células , Quinase I-kappa B , Animais , Humanos , Camundongos , Quinase I-kappa B/antagonistas & inibidores , Quinase I-kappa B/metabolismo , Linhagem Celular Tumoral , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Feminino , Sobrevivência Celular/efeitos dos fármacos , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras B/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras B/patologia , Criança , Adolescente , Ensaios Antitumorais Modelo de Xenoenxerto , Inibidores de Proteínas Quinases/farmacologia
10.
Sci Adv ; 10(23): eado1550, 2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38848358

RESUMO

The utilization of three-dimensional (3D) bioprinting technology to create a transplantable bioartificial liver emerges as a promising remedy for the scarcity of liver donors. This study outlines our strategy for constructing a 3D-bioprinted liver, using in vitro-expanded primary hepatocytes recognized for their safety and enhanced functional robustness as hepatic cell sources for bioartificial liver construction. In addition, we have developed bioink biomaterials with mechanical and rheological properties, as well as printing capabilities, tailored for 3D bioprinting. Upon heterotopic transplantation into the mesentery of tyrosinemia or 90% hepatectomy mice, our 3D-bioprinted liver effectively restored lost liver functions, consequently extending the life span of mice afflicted with liver injuries. Notably, the inclusion of an artificial blood vessel in our 3D-bioprinted liver allowed for biomolecule exchange with host blood vessels, demonstrating, in principle, the rapid integration of the bioartificial liver into the host vascular system. This model underscores the therapeutic potential of transplantation for the treatment of liver failure diseases.


Assuntos
Bioimpressão , Hepatócitos , Falência Hepática , Fígado , Impressão Tridimensional , Animais , Hepatócitos/metabolismo , Hepatócitos/transplante , Camundongos , Bioimpressão/métodos , Fígado/metabolismo , Falência Hepática/terapia , Engenharia Tecidual/métodos , Transplante de Fígado/métodos , Fígado Artificial , Modelos Animais de Doenças , Tirosinemias/terapia , Tirosinemias/metabolismo , Alicerces Teciduais/química
11.
Food Chem ; 454: 139741, 2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-38805922

RESUMO

The dual-frequency ultrasound-assisted enzymatic digestion (DUED) technique was developed for synchronous green extraction of five heavy metal ions in root vegetables. The combination of α-amylase, cellulase, and papain showed significant advantageous in extracting heavy metal ions. Under optimized dual-frequency ultrasonic conditions, the extraction rates of Cr, As, Cd, Pb, and Hg in carrots reached 99.04%, 105.88%, 104.65%, 104.10%, and 103.13% respectively. And the extraction process is highly efficient, completing in just 15 min. Compared to conventional microwave-assisted acid hydrolysis method, this technique eliminates the need for high-temperature concentrated acid, enhancing its environmental sustainability while maintaining mild reaction conditions, making it ideal for biosensors application. Additionally, simultaneous extraction and detection of four heavy metals in lotus roots were successfully achieved by using DUED and a fluorescent paper-based microfluidic chip. The obtained results are consistent with those obtained using conventional methods.


Assuntos
Metais Pesados , Raízes de Plantas , Verduras , Metais Pesados/isolamento & purificação , Metais Pesados/química , Verduras/química , Raízes de Plantas/química , alfa-Amilases/metabolismo , alfa-Amilases/química , Celulase/química , Celulase/metabolismo , Papaína/química , Papaína/metabolismo , Ultrassom , Contaminação de Alimentos/análise , Daucus carota/química
12.
J Anim Sci ; 1022024 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-38795007

RESUMO

The present study sought to assess the effects of manganese complexes with lysine and glutamic acid (Mn-LG) as manganese (Mn) sources on growth performance, trace element deposition, antioxidant capacity, and metacarpal strength in weaned piglets. The study involved 288 healthy Duroc × Landrace × Yorkshire piglets that were weaned at 25 to 28 d of age and weighed 8.66 ±â€…0.96 kg. These piglets were randomly divided into six groups: a control group (Mn-LG-0, receiving a basal diet without Mn supplementation), a Mn sulfate group (basal diet supplemented with 40 mg·kg-1 diet of Mn, Mn-S-40 group), and four Mn-LG groups (Mn-LG-20, Mn-LG-40, Mn-LG-60, Mn-LG-80, supplemented with 20, 40, 60, and 80 mg·kg-1 Mn from Mn-LG in the basal diet). Grouping began at weaning on the 0th day of the experiment. The corn-soybean-based basal diet during the early (days 0 to 14) and late (days 15 to 42) phases of the experiment contained 20.88 and 30.12 mg·kg-1 Mn, respectively. Blood samples were collected on days 14 and 42, and pigs were sacrificed for sample collection on day 42. The results indicated no significant differences in average daily gain, average daily feed intake, or feed-to-gain ratio among the groups (P > 0.05). The diarrhea rates of all Mn-LG groups and the Mn-S-40 group were significantly lower in the 0 to 14 d and during the entire experimental period than in the Mn-LG-0 group (P < 0.001). The Mn-LG-40 group exhibited a significant increase in liver Mn concentration and serum Mn superoxide dismutase (Mn-SOD) activity on day 42 (P < 0.01), as well as a significant decrease in fecal Mn concentration (P < 0.05), compared to those of the Mn-S-40 group. Significant differences (P < 0.05) were detected in the serum, liver, and fecal Mn concentrations, as well as in the serum and liver Mn-SOD activity, across the different Mn-LG groups. The serum and fecal Mn concentrations and serum Mn-SOD activity increased linearly or quadratically (P < 0.01) with increasing Mn-LG supplementation. No significant differences (P > 0.05) were found in kidney, heart, or metacarpal bone Mn concentrations or in bone strength indices. In summary, compared with the Mn-LG-0 diet, dietary supplementation with Mn-LG enhanced serum Mn deposition and Mn-SOD activity and decreased the incidence of diarrhea. Additionally, the fecal Mn concentration was lower in the Mn-LG group than in the inorganic group at equivalent dosages.


This research explored the effects of a manganese complex containing lysine and glutamic acid (Mn-LG) on various health parameters in weaned piglets. Utilizing samples of 288 piglets, the study investigated how Mn-LG supplementation influences growth performance, Mn deposition and emission, antioxidant capacity, and metacarpal strength. Key findings include an increase in serum Mn levels and Mn superoxide dismutase (Mn-SOD) activity, a reduction in diarrhea incidence, and no significant effects in bone strength indices in piglets receiving Mn-LG. Additionally, the fecal Mn concentration was notably lower in the Mn-LG group than in the group receiving inorganic Mn at equivalent dosages.


Assuntos
Ração Animal , Antioxidantes , Dieta , Suplementos Nutricionais , Ácido Glutâmico , Lisina , Manganês , Animais , Lisina/farmacologia , Lisina/administração & dosagem , Lisina/metabolismo , Ração Animal/análise , Manganês/farmacologia , Manganês/administração & dosagem , Manganês/metabolismo , Dieta/veterinária , Antioxidantes/metabolismo , Antioxidantes/farmacologia , Suplementos Nutricionais/análise , Suínos/crescimento & desenvolvimento , Ácido Glutâmico/farmacologia , Ácido Glutâmico/metabolismo , Masculino , Feminino , Fenômenos Fisiológicos da Nutrição Animal , Desmame , Distribuição Aleatória , Ossos Metacarpais/metabolismo , Ossos Metacarpais/efeitos dos fármacos
13.
Front Aging Neurosci ; 16: 1377406, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38694260

RESUMO

The worldwide incidence of cognitive impairment is escalating, yet no effective solutions for these afflictions have been discovered. Consequently, the importance of early identification and immediate intervention is heightened. Advanced eye movements-a form of voluntary eye movements that includes anti-saccades, memory-guided saccades, predictive saccades, pro-saccades and gap/overlap saccades, mediated by the cerebral cortex and subcortical pathways reflect cognitive levels and functions across different domains. In view of their objectivity, reproducibility, and non-invasive characteristics, advanced eye movement examination possesses significant prospective utility across a wide range of cognitive impairment. This paper extensively reviews various models associated with advanced eye movement examinations and their current applications in cognitive impairment such as Alzheimer's disease, Lewy body dementia and frontotemporal dementia. Advanced eye movement examination can serve as a biomarker for early screening diagnosis and research on cognitive impairment. In the future, combining advanced eye movement examination with neuropsychological scale assessment and other diagnostic methods may contribute to further early identification of these types of diseases.

14.
Int J Cardiol Cardiovasc Risk Prev ; 21: 200286, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38813099

RESUMO

Background: Ventricular arrhythmias (VAs) mainly occur in the early post-myocardial infarction (MI) period. However, studies examining the association between total myocardial ischemia time interval and the risk of new-onset VAs during a long-term follow-up are scarce. Methods: This study (symptom-to-balloon time and VEntricular aRrhYthmias in patients with STEMI, VERY-STEMI study) was a multicenter, observational cohort and real-world study, which included patients with ST-segment elevation MI (STEMI) undergoing percutaneous coronary intervention (PCI). The primary endpoint was cumulative new-onset VAs during follow-up. The secondary endpoints were the major adverse cardiovascular events (MACE) and changes in left ventricular ejection fraction (ΔLVEF, %). Results: A total of 517 patients with STEMI were included and 236 primary endpoint events occurred. After multivariable adjustments, compared to patients with S2BT of 24 h-7d, those with S2BT ≤ 24 h and S2BT > 7d had a lower risk of primary endpoint. RCS showed an inverted U-shaped relationship between S2BT and the primary endpoint, with an S2BT of 68.4 h at the inflection point. Patients with S2BT ≤ 24 h were associated with a lower risk of MACE and a 4.44 increase in LVEF, while there was no significant difference in MACE and LVEF change between the S2BT > 7d group and S2BT of 24 h-7d group. Conclusions: S2BT of 24 h-7d in STEMI patients was associated with a higher risk of VAs during follow-up. There was an inverted U-shaped relationship between S2BT and VAs, with the highest risk at an S2BT of 68.4 h.

15.
Artigo em Inglês | MEDLINE | ID: mdl-38807023

RESUMO

HSP70 exhibits neuroprotective, antioxidant, and anti-apoptotic properties, which are crucial in preventing spinal cord injury (SCI) induced by oxidative stress and apoptosis. In this study, we assessed the potential protective effects and underlying mechanisms of HSP70 on tert-butyl hydroperoxide (TBHP)-damaged PC12 cells in an in vitro model of SCI. To establish the model, PC12 cells were subjected to oxidative damage induced by TBHP, followed by overexpression of HSP70. Cell viability was assessed using the CCK8 kit, intracellular reactive oxygen species level was evaluated using a commercial kit, cell apoptosis was detected using the Annexin V-APC/7-ADD Apoptosis Detection Kit, and the oxidative stress level was determined using SOD and MDA assay kits. Western blot analysis was used to detect the expression levels of Bax, cleaved caspase-3, and Bcl-2 proteins. Furthermore, immunofluorescence staining and Western bolt were used to detect the expression levels of proteins associated with the Nrf2/HO-1 signaling pathway. We found that HSP70 overexpression reduced apoptosis and oxidative stress in TBHP-induced PC12 cells. Furthermore, it activated the Nrf2/HO-1 signaling pathway. In addition, the Nrf2 inhibitor ML385 attenuated the protective effects of HSP70 on TBHP-induced PC12 cells. In conclusion, HSP70 can partially alleviate TBHP-induced apoptosis and oxidative stress in PC12 cells by promoting the Nrf2/HO-1 signaling pathway.

16.
Clin Cancer Res ; 30(12): 2636-2646, 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38578683

RESUMO

PURPOSE: The current National Comprehensive Cancer Network (NCCN) guidelines recommend afatinib or osimertinib as the preferred first-line treatment strategy for patients with advanced NSCLC harboring EGFR p.G719X mutation. However, in the absence of head-to-head trials comparing afatinib with osimertinib in EGFR p.G719X-mutant patients, it is unclear which regimen is the preferred treatment option. EXPERIMENTAL DESIGN: A large cohort of 4,228 treatment-naïve patients with lung cancer who underwent targeted next-generation sequencing (NGS) testing was screened for EGFR p.G719X mutation. A multicenter cohort involving 68 EGFR p.G719X-mutant patients with advanced NSCLC and NGS profiling was retrospectively enrolled to evaluate clinical responses to afatinib (n = 37) and the third-generation EGFR-TKIs (n = 31). Ba/F3 cells stably expressing the EGFR p.G719A mutation were created to investigate the response to EGFR-TKIs in vitro. RESULTS: Concurrent EGFR p.E709X mutations, being the most frequent co-occurring EGFR mutation in EGFR p.G719X-mutant NSCLC (∼30%), exerted a detrimental effect on outcomes in patients treated with third-generation EGFR-TKI [G719X/E709X vs. G719X; objective response rate (ORR): 0.00% vs. 47.62%, P < 0.001; mPFS: 7.18 vs. 14.2 months, P = 0.04, respectively]. Conversely, no significant difference was found in the treatment efficacy of afatinib between EGFR p.G719X/E709X and EGFR p.G719X patients (G719X/E709X vs. G719X; ORR: 71.43% vs. 56.67%, P = 0.99; mPFS: 14.7 vs. 15.8 months, P = 0.69, respectively). In vitro experiments elucidated a resistant drug sensitivity and poor inhibition of EGFR phosphorylation in Ba/F3 cells expressing EGFR p.G719A/E709K mutation upon the third-generation EGFR-TKI treatment. CONCLUSIONS: Co-occurring EGFR p.E709X mutation mediated primary resistance to the third-generation EGFR-TKIs in EGFR p.G719X-mutant patients but remained sensitive to afatinib. A personalized treatment strategy should be undertaken based on the coexisting EGFR p.E709X mutation status.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Resistencia a Medicamentos Antineoplásicos , Receptores ErbB , Neoplasias Pulmonares , Mutação , Inibidores de Proteínas Quinases , Humanos , Receptores ErbB/genética , Receptores ErbB/antagonistas & inibidores , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Inibidores de Proteínas Quinases/uso terapêutico , Inibidores de Proteínas Quinases/farmacologia , Resistencia a Medicamentos Antineoplásicos/genética , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Feminino , Masculino , Pessoa de Meia-Idade , Idoso , Afatinib/uso terapêutico , Afatinib/farmacologia , Estudos Retrospectivos , Adulto , Idoso de 80 Anos ou mais , Sequenciamento de Nucleotídeos em Larga Escala , Linhagem Celular Tumoral , Compostos de Anilina/uso terapêutico , Compostos de Anilina/farmacologia , Acrilamidas/uso terapêutico , Acrilamidas/farmacologia
17.
Anal Bioanal Chem ; 416(15): 3509-3518, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38647692

RESUMO

Escherichia coli O157:H7 (E. coli O157:H7) is a foodborne pathogenic microorganism that is commonly found in the environment and poses a significant threat to human health, public safety, and economic stability worldwide. Thus, early detection is essential for E. coli O157:H7 control. In recent years, a series of E. coli O157:H7 detection methods have been developed, but the sensitivity and portability of the methods still need improvement. Therefore, in this study, a rapid and efficient testing platform based on the CRISPR/Cas12a cleavage reaction was constructed. Through the integration of recombinant polymerase amplification and lateral flow chromatography, we established a dual-interpretation-mode detection platform based on CRISPR/Cas12a-derived fluorescence and lateral flow chromatography for the detection of E. coli O157:H7. For the fluorescence detection method, the limits of detection (LODs) of genomic DNA and E. coli O157:H7 were 1.8 fg/µL and 2.4 CFU/mL, respectively, within 40 min. Conversely, for the lateral flow detection method, LODs of 1.8 fg/µL and 2.4 × 102 CFU/mL were achieved for genomic DNA and E. coli O157:H7, respectively, within 45 min. This detection strategy offered higher sensitivity and lower equipment requirements than industry standards. In conclusion, the established platform showed excellent specificity and strong universality. Modifying the target gene and its primers can broaden the platform's applicability to detect various other foodborne pathogens.


Assuntos
Sistemas CRISPR-Cas , Escherichia coli O157 , Limite de Detecção , Escherichia coli O157/genética , Escherichia coli O157/isolamento & purificação , DNA Bacteriano/análise , DNA Bacteriano/genética , Microbiologia de Alimentos/métodos , Proteínas Associadas a CRISPR/genética , Humanos , Endodesoxirribonucleases/genética
18.
Cryobiology ; 115: 104895, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38616031

RESUMO

The study is devoted to the effect of lowered resuscitation temperature (26 °C) on cryopreserved porcine adrenal glands functional activity in vitro and in vivo under xenotransplantation. The adrenals were collected from newborn pigs, cryopreserved with 5 % DMSO at a rate of 1 °C/min, resuscitated at 26 or 37 °C for 48 h (5 % CO2, DMEM), embedded into small intestinal submucosa, and transplanted to bilaterally adrenalectomized rats. It has been shown that the glands resuscitated at 26 °C have suppressed free-radical processes and can produce cortisol and aldosterone in vitro, and may lead to elevated blood levels of these hormones. Moreover, the adrenal grafts maintain blood glucose levels and promote the formation of glycogen stores. Thus, the resuscitation at 26 °C can improve the quality of grafts and favor the introduction and application of the cryopreserved organs and tissues for transplantation in clinical and experimental practice.


Assuntos
Glândulas Suprarrenais , Criopreservação , Hidrocortisona , Transplante Heterólogo , Animais , Glândulas Suprarrenais/metabolismo , Transplante Heterólogo/métodos , Criopreservação/métodos , Suínos , Hidrocortisona/sangue , Ratos , Glicemia/metabolismo , Glicemia/análise , Aldosterona/sangue , Aldosterona/metabolismo , Masculino , Glicogênio/metabolismo , Ressuscitação/métodos , Preservação de Órgãos/métodos , Crioprotetores/farmacologia , Dimetil Sulfóxido/farmacologia
19.
Acta Pharmacol Sin ; 2024 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-38684798

RESUMO

Colorectal cancer (CRC) is a prevalent form of gastrointestinal malignancy with challenges in chemotherapy resistance and side effects. Effective and low toxic drugs for CRC treatment are urgently needed. Ferroptosis is a novel mode of cell death, which has garnered attention for its therapeutic potential against cancer. Baicalein (5, 6, 7-trihydroxyflavone) is the primary flavone extracted from the dried roots of Scutellaria baicalensis that exhibits anticancer effects against several malignancies including CRC. In this study, we investigated whether baicalein induced ferroptosis in CRC cells. We showed that baicalein (1-64 µM) dose-dependently inhibited the viability of human CRC lines HCT116 and DLD1. Co-treatment with the ferroptosis inhibitor liproxstatin-1 (1 µM) significantly mitigated baicalein-induced CRC cell death, whereas autophagy inhibitor chloroquine (25 µM), necroptosis inhibitor necrostatin-1 (10 µM), or pan-caspase inhibitor Z-VAD-FMK (10 µM) did not rescue baicalein-induced CRC cell death. RNA-seq analysis confirmed that the inhibitory effect of baicalein on CRC cells is associated with ferroptosis induction. We revealed that baicalein (7.5-30 µM) dose-dependently decreased the expression levels of GPX4, key regulator of ferroptosis, in HCT116 and DLD1 cells by blocking janus kinase 2 (JAK2)/STAT3 signaling pathway via direct interaction with JAK2, ultimately leading to ferroptosis in CRC cells. In a CRC xenograft mouse model, administration of baicalein (10, 20 mg/kg, i.g., every two days for two weeks) dose-dependently inhibited the tumor growth with significant ferroptosis induced by inhibiting the JAK2/STAT3/GPX4 axis in tumor tissue. This study demonstrates that ferroptosis contributes to baicalein-induced anti-CRC activity through blockade of the JAK2/STAT3/GPX4 signaling pathway, which provides evidence for the therapeutic application of baicalein against CRC.

20.
Artigo em Inglês | MEDLINE | ID: mdl-38581337

RESUMO

Objective: With the improvement of living standards, consumers are paying more and more attention to the quality of rice. Traditional rice quality detection relies on human sensory judgment, which is inaccurate and inefficient. With the continuous development of molecular imaging technology, more and more scholars at home and abroad have begun to pay attention to its application in the nondestructive testing of agricultural products. Molecular imaging technology combines the advantages of spectral technology and image technology, which can achieve rapid, nondestructive and accurate detection of rice quality. In this paper, taking rice as the research object, we carried out nondestructive detection research on rice varieties, moisture and starch content using molecular imaging technology. We proposed a rapid detection method based on molecular imaging technology for rice variety identification, moisture content and starch content. Molecular images of the rice samples from four origins were obtained using a molecular imaging system, the regions of interest of the rice were identified and, spectral data, textural features and morphological features of the rice were extracted. Spectral, textural and morphological features were selected by principal component analysis (PCA), and nine feature wavelengths were obtained and an optimal model was established with an accuracy of 91.67%, which demonstrated the feasibility of molecular imaging. By comparing the models, the BCC-LS-SVR model based on the RB function had the highest accuracy with R2 of 0.989, RMSEP of 0.767%, R2 of 0.985, and RMSEC of 0.591%. Moreover, starchy rice was detected using molecular imaging. The PCA-SVR model based on the RBF kernel function had the highest accuracy with R2 of 0.989, RMSEC of 0.445%, R2 of 0.991, and RMSEP of 0.669%. Our models demonstrated high accuracy in identifying rice varieties, as well as quantifying moisture and starch content, showcasing the feasibility of molecular imaging technology in rice quality assessment. This research offers a rapid, nondestructive, and accurate method for rice quality assessment, promising significant benefits for agricultural producers and consumers.

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