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1.
Food Res Int ; 194: 114930, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39232541

RESUMEN

Ripened pu-erh tea is known to have beneficial hypoglycemic properties. However, it remains unclear whether the bioactive peptides produced during fermentation are also related to hypoglycemic potential. This study aimed to identify hypoglycemic peptides in ripened pu-erh tea and to elucidate their bioactive mechanisms using physicochemical property prediction, molecular docking, molecular dynamics simulations, and cell experiments. Thirteen peptides were identified by liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS). Among them, AADTDYRFS (AS-9) and AGDGTPYVR (AR-9) exhibited high α-glucosidase inhibitory activity, with half-maximal inhibitory concentration (IC50) values of 0.820 and 3.942 mg/mL, respectively. Molecular docking and dynamics simulations revealed that hydrogen bonding, hydrophobic interactions, and van der Waals forces assist peptides AS-9 and AR-9 in forming stable and tight complexes with α-glucosidase. An insulin-resistance (IR)-HepG2 cell model was established. AS-9 was non-toxic to IR-HepG2 cells and significantly increased the glucose consumption capacity, hexokinase, and pyruvate kinase activities of IR-HepG2 cells (p < 0.05). AS-9 alleviated glucose metabolism disorders and ameliorated IR by activating the IRS-1/PI3K/Akt signaling pathway and increasing the expression levels of MDM2, IRS-1, Akt, PI3K, GLUT4, and GSK3ß genes. In addition, no hemolysis of mice red blood cells red blood cells occurred at concentrations below 1 mg/mL. This work first explored hypoglycemic peptides in ripened pu-erh tea, providing novel insights for enhancing its functional value.


Asunto(s)
Inhibidores de Glicósido Hidrolasas , Hipoglucemiantes , Simulación del Acoplamiento Molecular , Péptidos , , Hipoglucemiantes/farmacología , Hipoglucemiantes/química , Animales , Té/química , Humanos , Células Hep G2 , Péptidos/química , Péptidos/farmacología , Inhibidores de Glicósido Hidrolasas/farmacología , Inhibidores de Glicósido Hidrolasas/química , Ratones , Simulación de Dinámica Molecular , Resistencia a la Insulina , Transducción de Señal/efectos de los fármacos , Proteínas Sustrato del Receptor de Insulina/metabolismo , Espectrometría de Masas en Tándem , alfa-Glucosidasas/metabolismo , Fermentación
3.
Sci China Life Sci ; 2024 Aug 29.
Artículo en Inglés | MEDLINE | ID: mdl-39225895

RESUMEN

Atherosclerosis is the pathological cause of atherosclerotic cardiovascular disease (ASCVD), which rapidly progresses during the cellular senescence. Sodium-glucose cotransporter 2 inhibitors (SGLT2is) reduce major cardiovascular events in patients with ASCVD and have potential antisenescence effects. Here, we investigate the effects of the SGLT2 inhibitor dapagliflozin on cellular senescence in atherosclerotic mice. Compared with ApoE-/- control mice treated with normal saline, those in the ApoE-/- dapagliflozin group, receiving intragastric dapagliflozin (0.1 mg kg-1 d-1) for 14 weeks, exhibited the reduction in the total aortic plaque area (48.8%±6.6% vs. 74.6%±8.0%, P<0.05), the decrease in the lipid core area ((0.019±0.0037) mm2vs. (0.032±0.0062) mm2, P<0.05) and in the percentage of senescent cells within the plaques (16.4%±3.7% vs. 30.7%±2.0%, P<0.01), while the increase in the thickness of the fibrous cap ((21.6±2.1) µm vs. (14.6±1.5) µm, P<0.01). Transcriptome sequencing of the aortic arch in the mice revealed the involvement of the PPARα and the fatty acid metabolic signaling pathways in dapagliflozin's mechanism of ameliorating cellular aging and plaque progression. In vitro, dapagliflozin inhibited the expression of PPARα and its downstream signal FABP4, by which the accumulation of senescent cells in human aortic smooth muscle cells (HASMCs) was reduced under high-fat conditions. This effect was accompanied by a reduction in the intracellular lipid content and alleviation of oxidative stress. However, these beneficial effects of dapagliflozin could be reversed by the PPARα overexpression. Bioinformatics analysis and molecular docking simulations revealed that dapagliflozin might exert its effects by directly interacting with the RXRA protein, thereby influencing the expression of the PPARα signaling pathway. In conclusion, the cellular senescence of aortic smooth muscle cells is potentially altered by dapagliflozin through the suppression of the RXRA-PPARα-FABP4 signaling pathway, resulting in a deceleration of atherosclerotic progression.

4.
Cardiovasc Diagn Ther ; 14(4): 478-488, 2024 Aug 31.
Artículo en Inglés | MEDLINE | ID: mdl-39263470

RESUMEN

Background: Patient-specific computer simulation of transcatheter aortic valve implantation (TAVI) predicts the interaction between an implanted device and the surrounding anatomy. In this study, we validated the predictive value of computer simulation for the frame deformation following a Venus-A TAVI implant in patients with pure aortic regurgitation (AR). Furthermore, we used the validated computational model to evaluate the anchoring mechanism within the same cohort. Methods: This was a retrospective study. FEops HEARTguide technology was used to simulate the virtual implantation of a Venus-A valve model in a patient-specific geometry. The predicted frame deformation was quantitatively compared to the postoperative device deformation at multiple levels. The outward forces acting on the frame were extracted for each patient and the total outward force acting around the aortic annular (AA) and sinotubular junction (STJ) planes were recorded. Results: Thirty patients were enrolled in the study with 10 in the migration group and 20 in the non-migration group. The dimensions of the simulated and observed frames had good correlations at Dmax (R2=0.88), Dmin (R2=0.91), perimeter (R2=0.92), and area (R2=0.92). The predicted outward force acting on the frame at the AA level was comparable between the migration and no-migration groups. The predicted outward force acting on the frame at the STJ level was always significantly higher in the migration group than the no migration group at different bandwidths: 3 mm (P=0.002), 5 mm (P=0.005), 10 mm (P=0.002). Conclusions: Patient-specific computer simulation of TAVI accurately predicted frame deformation in Chinese patients with pure AR. The forces at the STJ facilitated stabilization of the device within the aortic root, which might be used as a discriminator to identify patients at risk of device migration prior to intervention.

5.
Theranostics ; 14(13): 5219-5234, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39267791

RESUMEN

RATIONALE: Anesthetics are widely used for optimizing surgical conditions, postoperative pain management, and treating various chronic pain conditions. Tetracaine and decamethonium are representative drugs of local anesthetics and neuromuscular blocking agents, respectively. However, overdose and toxicity of the drugs always lead to serious adverse events. Thus, there is a strong demand for effective antidotes. METHODS: The binding interactions of amide naphthotubes with tetracaine and decamethonium were systematically studied using 1H NMR, ITC, and DFT calculations. The antidotal effects of amide naphthotube to tetracaine toxicity were assessed in vitro and in vivo, and the mechanism of detoxification was explored at a cellular level. Additionally, mouse models were established to evaluate the reversal activities of amide naphthotube on decamethonium-induced mortality and muscle relaxation, and the reversal mechanism was investigated through pharmacokinetic experiments. RESULTS: We have demonstrated that the anti-isomer of amide naphthotube exhibits significant binding affinities towards tetracaine (K a = 1.89×107 M-1) and decamethonium (K a = 1.01×107 M-1) in water. The host displayed good biocompatibility both in vitro and in vivo. The administration of amide naphthotube following tetracaine overdose in mouse models notably increased the overall survival rate, indicating its effective antidotal properties. The host could reverse the tetracaine-induced Na+ channels blockage at the cellular level. Moreover, the injection of amide naphthotube also reversed the mortality and paralysis induced by decamethonium in mouse models following a pharmacokinetic mechanism. CONCLUSION: An emerging artificial receptor, amide naphthotube, has strong binding affinities towards tetracaine and decamethonium. It functions as a supramolecular antidote for tetracaine poisoning and a reversal agent for decamethonium by selectively sequestering these compounds in vivo.


Asunto(s)
Antídotos , Tetracaína , Animales , Tetracaína/farmacología , Tetracaína/química , Ratones , Antídotos/farmacología , Antídotos/química , Amidas/química , Amidas/farmacología , Masculino , Anestésicos Locales/farmacología , Anestésicos Locales/química , Humanos , Bloqueantes Neuromusculares/química , Bloqueantes Neuromusculares/farmacología
6.
J Sustain Metall ; 10(3): 1127-1140, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39280577

RESUMEN

Hydrogen-based direct reduction (HyDR) of iron ores has attracted immense attention and is considered a forerunner technology for sustainable ironmaking. It has a high potential to mitigate CO2 emissions in the steel industry, which accounts today for ~ 8-10% of all global CO2 emissions. Direct reduction produces highly porous sponge iron via natural-gas-based or gasified-coal-based reducing agents that contain hydrogen and organic molecules. Commercial technologies usually operate at elevated pressure, e.g., the MIDREX process at 2 bar and the HyL/Energiron process at 6-8 bar. However, the impact of H2 pressure on reduction kinetics and microstructure evolution of hematite pellets during hydrogen-based direct reduction has not been well understood. Here, we present a study about the influence of H2 pressure on the reduction kinetics of hematite pellets with pure H2 at 700 °C at various pressures, i.e., 1, 10, and 100 bar under static gas exposure, and 1.3 and 50 bar under dynamic gas exposure. The microstructure of the reduced pellets was characterized by combining X-ray diffraction and scanning electron microscopy equipped with electron backscatter diffraction. The results provide new insights into the critical role of H2 pressure in the hydrogen-based direct reduction process and establish a direction for future furnace design and process optimization.

7.
Curr Res Food Sci ; 9: 100831, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39281340

RESUMEN

During the fermentation of ripened pu-erh tea (RPT), the composition of lipids and other compounds changes significantly. In this study, we conducted industrial fermentation of RPT and observed that the levels of water extract, tea polyphenols, free amino acids, catechins, caffeine, rutin, theophylline, luteolin, and myricetin decreased, while the level of soluble sugar increased. Additionally, the levels of gallic acid, quercetin, ellagic acid, and kaempferol first increased and then decreased during fermentation. We identified a total of 731 lipids, which were classified into seven categories using a lipomics method. Among these lipids, 85 with relatively high contents decreased, while 201 lipids with low contents increased after fermentation. This led to an overall decrease in the sum contents of lipids and dominant lipids, including glycerophospholipids and saccharolipids. We also detected 33 medium- and long-chain fatty acids, with α-linolenic acid (881.202 ± 12.13-1322.263 ± 19.78 µg/g), palmitic acid (797.275 ± 19.56-955.180 ± 30.49 µg/g), and linoleic acid (539.634 ± 15.551-706.869 ± 12.14 µg/g) being the predominant ones. Coenzymes Q9 (62.76-63.57 µg/g) and Q10 (50.82-59.33 µg/g) were also identified in the fermentation process. Our findings shed light on the changes in lipids during the fermentation of RPT and highlight the potential bio-active compounds, such as α-linolenic acid, linoleic acid, Coenzymes Q9, and Q10, in ripened pu-erh tea. This contributes to a better understanding of the fermentation mechanism for RPT.

8.
Nat Commun ; 15(1): 7664, 2024 Sep 03.
Artículo en Inglés | MEDLINE | ID: mdl-39227567

RESUMEN

The immunosuppressive tumor microenvironment (TME) remains a major obstacle to tumor control and causes suboptimal responses to immune checkpoint blockade (ICB) therapy. Thus, developing feasible therapeutic strategies that trigger inflammatory responses in the TME could improve the ICB efficacy. Mitochondria play an essential role in inflammation regulation and tumor immunogenicity induction. Herein, we report the discovery and characterization of a class of small molecules that can recapitulate aqueous self-assembly behavior, specifically target cellular organelles (e.g., mitochondria), and invigorate tumor cell immunogenicity. Mechanistically, this nanoassembly platform dynamically rewires mitochondria, induces endoplasmic reticulum stress, and causes apoptosis/paraptosis-associated immunogenic cell death. After treatment, stressed and dying tumor cells can act as prophylactic or therapeutic cancer vaccines. In preclinical mouse models of cancers with intrinsic or acquired resistance to PD-1 blockade, the local administration of nanoassemblies inflames the immunologically silent TME and synergizes with ICB therapy, generating potent antitumor immunity. This chemically programmed small-molecule immune enhancer acts distinctly from regular cytotoxic therapeutics and offers a promising strategy for synchronous and dynamic tailoring of innate immunity to achieve traceless cancer therapy and overcome immunosuppression in cancers.


Asunto(s)
Mitocondrias , Neoplasias , Microambiente Tumoral , Animales , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Ratones , Microambiente Tumoral/efectos de los fármacos , Microambiente Tumoral/inmunología , Humanos , Línea Celular Tumoral , Neoplasias/inmunología , Neoplasias/tratamiento farmacológico , Inhibidores de Puntos de Control Inmunológico/farmacología , Estrés del Retículo Endoplásmico/efectos de los fármacos , Estrés del Retículo Endoplásmico/inmunología , Apoptosis/efectos de los fármacos , Femenino , Muerte Celular Inmunogénica/efectos de los fármacos , Ratones Endogámicos C57BL , Nanopartículas/química , Vacunas contra el Cáncer/inmunología , Vacunas contra el Cáncer/administración & dosificación , Inmunoterapia/métodos
9.
Foods ; 13(17)2024 Sep 04.
Artículo en Inglés | MEDLINE | ID: mdl-39272573

RESUMEN

Cronobacter sakazakii (C. sakazakii) is a foodborne pathogen capable of causing severe infections in newborns. The PhoP/PhoQ two-component system exerts a significant influence on bacterial virulence. This study aimed to investigate the impact of the PhoP/PhoQ system on intestinal inflammation in neonatal mice induced by C. sakazakii. Neonatal mice were infected orally by C. sakazakii BAA-894 (WT), a phoPQ-gene-deletion strain (ΔphoPQ), and a complementation strain (ΔphoPQC), and the intestinal inflammation in the mice was monitored. Deletion of the phoPQ gene reduced the viable count of C. sakazakii in the ileum and alleviated intestinal tissue damage. Moreover, caspase-3 activity in the ileum of the WT- and ΔphoPQC-infected mice was significantly elevated compared to that of the ΔphoPQ and control groups. ELISA results showed elevated levels of TNF-α and IL-6 in the ileum of the mice infected with WT and ΔphoPQC. In addition, deletion of the phoPQ gene in C. sakazakii resulted in a down-regulation of inflammatory genes (IL-1ß, TNF-α, IL-6, NF-κB p65, TLR4) within the ileum and decreased inflammation by modulating the TLR4/NF-κB pathway. It is suggested that targeting the PhoP/PhoQ two-component system could be a potential strategy for mitigating C. sakazakii-induced neonatal infections.

10.
Nat Plants ; 2024 Sep 10.
Artículo en Inglés | MEDLINE | ID: mdl-39256564

RESUMEN

Cells harbour numerous receptor pathways to respond to diverse stimuli, yet often share common downstream signalling components. Mitogen-activated protein kinase (MPK) cascades are an example of such common hubs in eukaryotes. How such common hubs faithfully transduce distinct signals within the same cell-type is insufficiently understood, yet of fundamental importance for signal integration and processing in plants. We engineered a unique genetic background allowing direct comparisons of a developmental and an immunity pathway in one cell-type, the Arabidopsis root endodermis. We demonstrate that the two pathways maintain distinct functional and transcriptional outputs despite common MPK activity patterns. Nevertheless, activation of different MPK kinases and MPK classes led to distinct functional readouts, matching observed pathway-specific readouts. On the basis of our comprehensive analysis of core MPK signalling elements, we propose that combinatorial activation within the MPK cascade determines the differential regulation of an endodermal master transcription factor, MYB36, that drives pathway-specific gene activation.

11.
Stem Cell Res Ther ; 15(1): 293, 2024 Sep 11.
Artículo en Inglés | MEDLINE | ID: mdl-39256850

RESUMEN

BACKGROUND: Understanding the role of cytokines in tooth development is critical for advancing dental tissue engineering. Fibroblast growth factor 9 (FGF9) is the only FGF consistently expressed throughout dental epithelial tissue, from the initiation of tooth bud formation to tooth maturation. However, mice lacking Fgf9 (Fgf9-/-) surprisingly show no obvious abnormalities in tooth development, suggesting potential compensation by other FGFs. Here we report findings from an Fgf9S99N mutation mouse model, a loss-of-function mutation with a dominant negative effect. Our study reveals that Fgf9 is crucial for dental epithelial stem cell (DESC) survival and enamel formation. METHODS: To dissect the role of Fgf9 in tooth development, we performed the micro-CT, histomorphological analysis and gene expression assay in mice and embryos with S99N mutation. In addition, we assessed the effect of FGF9 on the DESC survival and dental epithelial differentiation by DESC sphere formation assay and tooth explant culture. Cell/tissue culture methods, gene expression analysis, specific inhibitors, and antibody blockage analysis were employed to explore how Fgf9 regulates enamel differentiation and DESC survival through both direct and indirect mechanisms. RESULTS: The Fgf9S99N mutation in mice led to reduced ameloblasts, impaired enamel formation, and increased apoptosis in the cervical loop (CL). DESC sphere culture experiments revealed that FGF9 facilitated DESC survival via activating ERK/CREB signaling, without affecting cell proliferation. Furthermore, in vitro tissue culture experiments demonstrated that FGF9 promoted enamel formation in a manner dependent on the presence of mesenchyme. Interestingly, FGF9 stimulation inhibited enamel formation in isolated enamel epithelia and DESC spheres. Further investigation revealed that FGF9 supports DESC survival and promotes amelogenesis by stimulating the secretion of FGF3 and FGF10 in dental mesenchymal cells via the MAPK/ERK signaling pathway. CONCLUSIONS: Our study demonstrates that Fgf9 is essential for DESC survival and enamel formation. Fgf9 performs as a dual-directional regulator of the dental enamel epithelium, not only inhibiting DESC differentiation into ameloblasts to preserve the stemness of DESC, but also promoting ameloblast differentiation through epithelial-mesenchymal interactions.


Asunto(s)
Esmalte Dental , Células Epiteliales , Factor 9 de Crecimiento de Fibroblastos , Células Madre , Animales , Factor 9 de Crecimiento de Fibroblastos/metabolismo , Factor 9 de Crecimiento de Fibroblastos/genética , Ratones , Esmalte Dental/metabolismo , Células Madre/metabolismo , Células Madre/citología , Células Epiteliales/metabolismo , Incisivo/metabolismo , Supervivencia Celular , Diferenciación Celular
12.
ACS Omega ; 9(34): 36497-36508, 2024 Aug 27.
Artículo en Inglés | MEDLINE | ID: mdl-39220477

RESUMEN

Plant oil-based vitrimer is an innovative and sustainable polymer with wide-ranging potential applications in the field of advanced materials. However, its restricted application is caused by the poor mechanical properties and the need for catalysts during preparation. Using renewable cardanol as the raw material, epoxy cardanol glycidyl ether (ECGE) with an end epoxide group was obtained by the clicking reaction and epoxidation reaction. After the application of citric acid (CA), ECGE was successfully cured, resulting in the production of fully biobased ECGE-CA vitrimers. This material does not require a catalyst, possesses self-healing properties, and exhibits high mechanical strength. On account of the introduction of hydroxyl groups in citric acid, plenty of hydrogen bonds are formed, allowing the topological network rearrangement of the material in the absence of a catalyst. Recyclable adhesives and repairable materials, vitrimer polymers have good shape memory, self-healing, and recyclability since of their dynamic ester and hydroxyl bonds.

13.
Acta Pharm Sin B ; 14(8): 3385-3415, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39220868

RESUMEN

Bile acids (BAs) are synthesized by the host liver from cholesterol and are delivered to the intestine, where they undergo further metabolism by gut microbes and circulate between the liver and intestines through various transporters. They serve to emulsify dietary lipids and act as signaling molecules, regulating the host's metabolism and immune homeostasis through specific receptors. Therefore, disruptions in BA metabolism, transport, and signaling are closely associated with cholestasis, metabolic disorders, autoimmune diseases, and others. Botanical triterpenoids and steroids share structural similarities with BAs, and they have been found to modulate BA metabolism, transport, and signaling, potentially exerting pharmacological or toxicological effects. Here, we have updated the research progress on BA, with a particular emphasis on new-found microbial BAs. Additionally, the latest advancements in targeting BA metabolism and signaling for disease treatment are highlighted. Subsequently, the roles of botanical triterpenoids in BA metabolism, transport, and signaling are examined, analyzing their potential pharmacological, toxicological, or drug interaction effects through these mechanisms. Finally, a research paradigm is proposed that utilizes the gut microbiota as a link to interpret the role of these important natural products in BA signaling.

14.
Int J Hyperthermia ; 41(1): 2362998, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39128847

RESUMEN

BACKGROUND: Focused ultrasound ablation surgery (FUAS) has been widely employed to treat patients with uterine fibroid (UF). This study aimed to estimate myometrial stiffness changes in patients who received FUAS for UFs or myomectomy (ME) and compare the recovery of surrounding myometrium between FUAS and ME groups. Our results may provide more evidence for guiding the proper conception timing in patients with UF. METHODS: This study enrolled 173 patients from May 2022 to August 2023. Shear wave elastography (SWE) was used to dynamically monitor myometrial elasticity changes in patients before and after surgery. Moreover, our study monitored and analyzed the stiffness changes in the targeted fibroid after FUAS, as well as in the myometrium around after FUAS or ME. RESULTS: The stiffness of the myometrium around the resected fibroid was significantly higher than at the preoperative level until 6 months. Conversely, the stiffness of the surrounding myometrium was only temporarily increased 1 day after FUAS. The comparison between FUAS and ME groups regarding the stiffness of the surrounding myometrium showed that nonsignificant differences were detected between the two groups before the treatment. The stiffness of the surrounding myometrium in the ME group was statistically significantly higher than that of the FUAS group 1 day as well as 1, 3, and 6 months after the treatment, respectively. CONCLUSION: The FUAS had less impact on the surrounding myometrium than the ME, which may be more conducive to the recovery of myometrial elasticity in patients with UF.


Asunto(s)
Elasticidad , Leiomioma , Miometrio , Miomectomía Uterina , Humanos , Femenino , Leiomioma/cirugía , Leiomioma/diagnóstico por imagen , Miometrio/cirugía , Miometrio/diagnóstico por imagen , Adulto , Miomectomía Uterina/métodos , Ultrasonido Enfocado de Alta Intensidad de Ablación/métodos , Persona de Mediana Edad , Neoplasias Uterinas/cirugía , Diagnóstico por Imagen de Elasticidad/métodos
15.
ACS Appl Mater Interfaces ; 16(35): 46834-46843, 2024 Sep 04.
Artículo en Inglés | MEDLINE | ID: mdl-39163543

RESUMEN

Poly(aryl ether) materials are used in a wide range of applications in the communications and microelectronics fields for their outstanding mechanical and dielectric properties. In order to further improve the comprehensive performance, this work reports a series of cross-linkable poly(aryl ether)s (UCL-PAEn) containing trifluoroisopropyl and perfluorobiphenyl structures using 2,2-bis(4-hydroxyphenyl)hexafluoropropane, 2,2'-diallyl bisphenol A, and perfluorobiphenyl as starting materials. Their chemical structures and the effect of changes in the allyl content on the properties are thoroughly investigated. Owing to the introduction of fluorine atoms and cross-linked networks, the cross-linked poly(aryl ether) films present low dielectric constants (Dk = 1.93-2.24 at 1 MHz), low water absorption (0.14% -0.25%), and hydrophobic film surfaces (94.3-99.4°). Additionally, because of the presence of cross-linked networks, the CL-PAEn films exhibit superior thermal stability, with the 5% weight loss temperatures all above 445 °C and the maximum thermal decomposition rate temperatures all above 550 °C. The cross-linked films also demonstrate excellent mechanical properties, with tensile strength in the range of 57.1 -146.7 MPa and tensile modulus in the range of 1.8 GPa-4.5 GPa.

16.
Biochim Biophys Acta Mol Cell Res ; 1871(8): 119820, 2024 Aug 18.
Artículo en Inglés | MEDLINE | ID: mdl-39163918

RESUMEN

The role of micropeptide in cardiomyocyte proliferation remains unknown. We found that MPM (micropeptide in mitochondria) was highly expressed in cardiomyocytes. Compared to MPM+/+ mice, MPM knockout (MPM-/-) mice exhibited reduction in left ventricular (LV) mass, myocardial thickness and LV fractional shortening. RNA-sequencing analysis in H9c2, a rat cardiomyocyte cell line, identified downregulation of cell cycle-promoting genes as the most significant alteration in MPM-silencing cells. Consistently, gain- and loss-of-function analyses in H9c2 cells revealed that cardiomyocyte proliferation was repressed by silencing MPM but was promoted by overexpressing MPM. Moreover, the cardiomyocytes in the hearts of MPM-/- mice displayed reduced proliferation rates. Mechanism investigations disclosed that MPM is crucial for AKT activation in cardiomyocytes. We also identified an interaction between MPM and PTPMT1, and found that silencing PTPMT1 attenuated the effect of MPM in activating the AKT pathway, whereas inhibition of the AKT pathway abrogated the role of MPM in promoting cardiomyocyte proliferation. Collectively, these results indicate that MPM may promote cardiomyocyte proliferation and thus heart growth by interacting with PTPMT1 to activate the AKT pathway. Our findings identify the novel function and regulatory network of MPM and highlight the importance of micropeptides in cardiomyocyte proliferation and heart growth.

17.
Sci Total Environ ; 951: 175563, 2024 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-39153620

RESUMEN

Institutional controls, as an important measure for risk management of contaminated sites, is widely used in site management by the United States, Canada and European countries. At present, some regions in China have also begun to explore the implementation of institutional controls, but its path, safeguard mechanism, and tracking evaluation are still unclear. Based on China's unique contaminated site remediation control system and land management system, this paper proposes a framework for the whole life cycle institutional controls of China's contaminated sites: (1) evaluate the need for institutional controls; (2) establish the objectives of institutional controls; (3) identify the restrictive requirements of institutional controls; (4) establish the implementation form of institutional controls; and (5) regularly review the effectiveness of institutional controls. To demonstrate the applicability of the institutional control framework, a case demonstration study was conducted at a petrochemical contaminated site in China. By analyzing the information on residual pollutants after the implementation of risk management measures at the site, the exposure pathways and hazards in case of re-release, and the engineering facilities, we proposed eight restrictive requirements, including the prohibition of disturbing and damaging the clean and planted soil layers of the site and the protection of long-term monitoring wells. At the same time, we constructed a multi-departmental pathway to implement institutional controls in conjunction with ecological environment, natural resources and housing departments to ensure effective implementation of institutional controls. Eventually, we summarized a set of replicable and generalizable institutional controls application models, which provide valuable theoretical and practical support for China and other local governments in the implementation of institutional controls at contaminated sites.

18.
J Clin Apher ; 39(4): e22140, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39188020

RESUMEN

This meta-analysis aims to evaluate the effectiveness of the double plasma molecular adsorption system (DPMAS) in combination with plasma exchange (PE) compared to plasma exchange alone in the treatment of Acute-on-Chronic liver failure (LF) caused by hepatitis B. Until August 31, 2023, a comprehensive search of databases including Embase, Chinese Medical Journal Full-text Database, China Biomedical Literature Database, Wan Fang Medical Network, PubMed, and the Cochrane Library was carried out using keywords like "liver failure," "acute-on-chronic liver failure," "PE," "DPMAS," and related terms. The quality of the included studies was evaluated using QUADS (quality assessment of diagnostic accuracy studies). Software Revman 5.3 was used to examine the data, while Stata 15.1 was used to run Egger's test. Following thorough screening, 452 patients who received PE alone and 429 patients who received DPMAS in addition to PE were included. Every study that was included was of a high caliber. When comparing the DPMAS plus PE group to the PE alone group, the total bilirubin reduction was considerably higher (mean difference [MD] = -49.09, 95% confidence interval [CI]: -54.84 to -43.35, p < .00001). Prothrombin activity (PTA; MD = -1.53, 95% CI: -3.29 to -0.22, p = .09), albumin (ALB; MD = -0.58, 95% CI: -1.57 to 0.41, p = .25), prothrombin time (PT; MD = -0.07, 95% CI: -1.47 to 1.34, p = .92), and platelet count (PLT; MD = -0.08, 95% CI: -1.33 to 1.66, p = .90) did not differ significantly. The improvement in international standardized ratio (INR) was significantly greater in the PE group (MD = 0.07, 95% CI (0.03, 0.10), p = .0001). When combined with DPMAS, PE has been shown to be more effective in lowering total bilirubin levels. PE can also lower INR in individuals who have hepatitis B-related ACLF. This therapeutic strategy also lessens the need for plasma transfusions.


Asunto(s)
Insuficiencia Hepática Crónica Agudizada , Hepatitis B , Intercambio Plasmático , Femenino , Humanos , Masculino , Insuficiencia Hepática Crónica Agudizada/sangre , Insuficiencia Hepática Crónica Agudizada/etiología , Insuficiencia Hepática Crónica Agudizada/terapia , Adsorción , Bilirrubina/sangre , Hepatitis B/sangre , Hepatitis B/complicaciones , Hepatitis B/terapia , Intercambio Plasmático/instrumentación , Intercambio Plasmático/métodos , Resultado del Tratamiento
19.
J Pharm Biomed Anal ; 251: 116442, 2024 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-39197206

RESUMEN

Polygala tenuifolia is a well-known traditional Chinese medicine. Polygala tenuifolia polysaccharide (PTP), as one of its main active ingredients, has excellent neuroprotective activity. PTP improved the disruption of the endogenous metabolites and gut microbiota caused by Alzheimer's disease (AD). Specifically, untargeted metabolomics results showed that 19 metabolites such as leukotriene B4, vanylglycol, and cer(d18:1/18:0) are significantly reduced, and 2 metabolites are elevated. It was significantly enriched in Sphingolipid metabolism, Glycerophospholipid metabolism, Tyrosine metabolism, and Arachidonic acid metabolism. Meanwhile, 16S rDNA analysis showed that PTP treatment significantly increased the relative abundance of bacteria such as Alistipes, Lachnospiraceae_NK4A136_group, and Lachnospiraceae_UCG-006. In addition, Spearman analysis showed that significant changes in gut microbiota were closely related to differential endogenous metabolites.


Asunto(s)
Enfermedad de Alzheimer , Microbioma Gastrointestinal , Metabolómica , Polygala , Polisacáridos , Microbioma Gastrointestinal/efectos de los fármacos , Animales , Polygala/química , Ratones , Polisacáridos/farmacología , Metabolómica/métodos , Masculino , Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/metabolismo , Enfermedad de Alzheimer/microbiología , Bacterias/efectos de los fármacos , Bacterias/clasificación , Bacterias/metabolismo , Modelos Animales de Enfermedad , Fármacos Neuroprotectores/farmacología , Medicamentos Herbarios Chinos/farmacología , ARN Ribosómico 16S/genética
20.
J Food Prot ; 87(10): 100320, 2024 Aug 28.
Artículo en Inglés | MEDLINE | ID: mdl-39214464

RESUMEN

Limu smoked chicken is a traditional Chinese delicacy; however, polycyclic aromatic hydrocarbons (PAHs) are generated during the smoking process. We developed a pyrolysis process for pear wood liquid smoke with minimal PAH generation. Pear wood liquid smoke products were prepared under different pyrolysis conditions in a self-made pyrolysis reactor, and the total phenol, carbonyl compound, total acid, and PAH contents and PAH toxicity risk were evaluated. With increasing temperatures, the toxicity equivalent ΣPAH of the smoke liquid reached 3.004 µg/kg. With increasing particle sizes, the total phenol content reached 1.6 mg/mL; the phenol content was 5.95 mg/mL. With increasing particle sizes, the toxicity equivalent ΣPAHs of the smoke liquor reached 2.441 µg/kg. The optimal parameters for treating pear wood smoke liquid in the thermal reaction device were a pyrolysis temperature of pear wood of >350 °C, particle size of S2, and sucrose content of 8%.

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