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1.
Int J Biol Macromol ; : 132190, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38723820

RESUMO

This study describes the synthesis of Chitosan - corn protein (CSZ-TG) composites using TG enzyme (TG) as a cross-linking agent and the preparation of chitosan-based composite membrane material (CSZEO-TG) by blending citrus essential oil (EO) with the synthesized CSZ-TG. The prepared composite membrane material was used for fresh strawberry preservation and characterized by scanning electron microscopy, Fourier transform infrared spectroscopy, X-spectral diffraction, tensile properties, and water vapor and CO2 permeability. Scanning electron microscopy results showed a smooth surface of the composite membrane material after the addition of TG enzyme, while Fourier transforms infrared spectroscopy results showed a structural change of the composite membrane material after the addition of corn protein (Z). The tensile results showed an increase in the tensile strength of the composite membrane material after the addition of TG enzyme, while the flexibility of the composite membrane material was enhanced after the addition of EO. Compared with the pure chitosan membrane (CS), the water vapor and CO2 barrier properties of the composite membrane material after the addition of Z, TG, and EO did not change much, and they all showed better water vapor barrier properties. The results of the antioxidant analysis of the solution of the CSZEO-TG composite membrane material showed that the composite membrane material had efficient antioxidant properties. The effects of the composite film material on the storage period and quality of strawberries were evaluated by the indicators of weight loss, hardness, decay rate, soluble solids, titratable acid content, MDA content, and the content of four enzymes, SOD, POD, PPO and CAT. Comprehensive freshness data analysis showed that CSZEO-TG had the best freshness preservation performance and effectively extended the shelf life of strawberries.

3.
Nature ; 627(8002): 67-72, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38448698

RESUMO

Ordinary metals contain electron liquids within well-defined 'Fermi' surfaces at which the electrons behave as if they were non-interacting. In the absence of transitions to entirely new phases such as insulators or superconductors, interactions between electrons induce scattering that is quadratic in the deviation of the binding energy from the Fermi level. A long-standing puzzle is that certain materials do not fit this 'Fermi liquid' description. A common feature is strong interactions between electrons relative to their kinetic energies. One route to this regime is special lattices to reduce the electron kinetic energies. Twisted bilayer graphene1-4 is an example, and trihexagonal tiling lattices (triangular 'kagome'), with all corner sites removed on a 2 × 2 superlattice, can also host narrow electron bands5 for which interaction effects would be enhanced. Here we describe spectroscopy revealing non-Fermi-liquid behaviour for the ferromagnetic kagome metal Fe3Sn2 (ref. 6). We discover three C3-symmetric electron pockets at the Brillouin zone centre, two of which are expected from density functional theory. The third and most sharply defined band emerges at low temperatures and binding energies by means of fractionalization of one of the other two, most likely on the account of enhanced electron-electron interactions owing to a flat band predicted to lie just above the Fermi level. Our discovery opens the topic of how such many-body physics involving flat bands7,8 could differ depending on whether they arise from lattice geometry or from strongly localized atomic orbitals9,10.

4.
Biomedicines ; 12(3)2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38540274

RESUMO

The emergence of castration-resistant prostate cancer (CRPC) following androgen deprivation therapy (ADT) is associated with increased malignancy and limited treatment options. This study aims to investigate potential connections between immune cell infiltration and inflammatory cytokines with the YAP1/AR/PSA axis by exploring their interactions with autophagy. Our research reveals heightened levels of Yes-associated protein 1 (YAP1) expression in CRPC tissues compared with tissues from androgen-dependent prostate cancer (ADPC) and benign prostate hyperplasia (BPH). Additionally, a correlation was observed between YAP1 and PSA expressions in CRPC tissues, suggesting that YAP1 may exert a regulatory influence on PSA expression within CRPC. Enhanced YAP1 expression in C4-2 cells resulted in the upregulation of androgen receptor (AR) nuclear translocation and intracellular prostate-specific antigen (PSA) levels. Conversely, the suppression of YAP1 led to a decrease in PSA expression, suggesting that YAP1 may positively regulate the PSA in castration-resistant prostate cancer (CRPC) by facilitating AR nuclear import. The modulation of the autophagy activity exerts a significant impact on the expression levels of YAP1, the AR, and the PSA. Moreover, recent advancements in immunity and inflammation studies present promising avenues for potential therapies targeting prostate cancer (PC).

5.
Pharmacol Res ; 203: 107162, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38554788

RESUMO

In American men, the incidence of prostate cancer (PC) is the highest among all types of cancer, making it the second leading cause of mortality associated with cancer. For advanced or metastatic PC, antiandrogen therapies are standard treatment options. The administration of these treatments unfortunately carries the potential risk of inducing neuroendocrine prostate cancer (NEPC). Neuroendocrine differentiation (NED) serves as a crucial indicator of prostate cancer development, encompassing various factors such as phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR), Yes-associated protein 1 (YAP1), AMP-activated protein kinase (AMPK), miRNA. The processes of autophagy and ferroptosis (an iron-dependent form of programmed cell death) play pivotal roles in the regulation of various types of cancers. Clinical trials and preclinical investigations have been conducted on many signaling pathways during the development of NEPC, with the deepening of research, autophagy and ferroptosis appear to be the potential target for regulating NEPC. Due to the dual nature of autophagy and ferroptosis in cancer, gaining a deeper understanding of the developmental programs associated with achieving autophagy and ferroptosis may enhance risk stratification and treatment efficacy for patients with NEPC.


Assuntos
Autofagia , Ferroptose , Neoplasias da Próstata , Humanos , Ferroptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Masculino , Neoplasias da Próstata/patologia , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/metabolismo , Animais , Transdução de Sinais/efeitos dos fármacos , Antineoplásicos/uso terapêutico , Antineoplásicos/farmacologia , Tumores Neuroendócrinos/tratamento farmacológico , Tumores Neuroendócrinos/patologia , Tumores Neuroendócrinos/metabolismo
6.
Biomater Sci ; 12(6): 1425-1448, 2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38374788

RESUMO

To date, organ transplantation remains an effective method for treating end-stage diseases of various organs. In recent years, despite the continuous development of organ transplantation technology, a variety of problems restricting its progress have emerged one after another, and the shortage of donors is at the top of the list. Bioprinting is a very useful tool that has huge application potential in many fields of life science and biotechnology, among which its use in medicine occupies a large area. With the development of bioprinting, advances in medicine have focused on printing cells and tissues for tissue regeneration and reconstruction of viable human organs, such as the heart, kidneys, and bones. In recent years, with the development of organ transplantation, three-dimensional (3D) bioprinting has played an increasingly important role in this field, giving rise to many unsolved problems, including a shortage of organ donors. This review respectively introduces the development of 3D bioprinting as well as its working principles and main applications in the medical field, especially in the applications, and advancements and challenges of 3D bioprinting in organ transplantation. With the continuous update and progress of printing technology and its deeper integration with the medical field, many obstacles will have new solutions, including tissue repair and regeneration, organ reconstruction, etc., especially in the field of organ transplantation. 3D printing technology will provide a better solution to the problem of donor shortage.


Assuntos
Bioimpressão , Transplante de Órgãos , Humanos , Engenharia Tecidual/métodos , Bioimpressão/métodos , Medicina Regenerativa , Impressão Tridimensional
7.
iScience ; 27(1): 108713, 2024 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-38226156

RESUMO

The development of castration-resistant prostate cancer (CRPC) is driven by intricate genetic and epigenetic mechanisms. Traf2- and Nck-interacting kinase (TNIK) has been reported as a serine/threonine kinase associated with tumor cell proliferation or unfavorable cancer behavior. The microarray approach revealed a substantial upregulation of TNIK expression levels, enabling us to investigate the functional behaviors of the TNIK gene in CRPC. Specifically, we discovered that AR suppresses TNIK gene transcription in LNCaP and C4-2 cells by forming a complex with H3K27me3. Following the reduction of AR levels induced by androgen deprivation therapy (ADT), TNIK is recruited to activate EGFR signaling through phosphorylation in C4-2 cells, thereby promoting CRPC progression. Our findings unveil a regulatory role of AR as a repressor for TNIK while also highlighting how TNIK activates the EGFR pathway via phosphorylation to drive CRPC progression. Consequently, targeting TNIK may represent an appealing therapeutic strategy for CRPC.

8.
Int J Biol Macromol ; 259(Pt 1): 129213, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38184052

RESUMO

The wound therapy based on antibiotic delivery inevitably leads to the emergence of drug resistance. Hydrogel biomaterials with inherent antibacterial activities have emerged as promising candidates for addressing this issue. However, developing an inherently antibacterial hydrogel through simple and facile strategies to promote localized wound infection healing remains a challenge. In this study, we successfully constructed antimicrobial cationic hydrogels with self-healing and injectable properties through physically and chemically dual-crosslinked networks. The networks were formed by the copolymers poly[(di(ethylene glycol) methyl ether methacrylate)-co-(4-formylphenyl methacrylate)-co-(2-(methacryloyloxy)ethyl]trimethylammonium chloride solution)] (PDFM) and poly[(di(ethylene glycol) methyl ether methacrylate)-co-(2-aminoethyl methacrylate hydrochloride)-co-(2-(((6-(6-methyl-4[1H]pyrimidionylureido) hexyl)carbamoyl)oxy)ethyl methacrylate)] (PDAU). The hydrogel systems effectively facilitate the regeneration and healing of infected wounds through the contact bactericidal feature of quaternary ammonium cations. The presence of Schiff base bonds in the injectable hydrogels imparts remarkable pH responsiveness and self-healing properties. In vitro experiments verified their intrinsic antibacterial activities along with their favorable cytocompatibility and hemocompatibility in both in vitro and in vivo. In addition, the hydrogel significantly accelerated the healing of bacterially infected in a full-thickness skin wound. This facilely prepared dual-crosslinked hydrogel, without antibiotics loading, holds significant prospects for treating infected wounds.


Assuntos
Anti-Infecciosos , Éteres Metílicos , Hidrogéis/farmacologia , Hidrogéis/química , Anti-Infecciosos/farmacologia , Cicatrização , Antibacterianos/química , Metacrilatos/farmacologia , Etilenoglicóis
9.
Microorganisms ; 11(12)2023 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-38137990

RESUMO

African swine fever, which is induced by the African swine fever virus (ASFV), poses a significant threat to the global pig industry due to its high lethality in domestic pigs and wild boars. Despite the severity of the disease, there is a lack of effective vaccines and drugs against the ASFV. The p72 protein, constituting 31 to 33% of the total virus particle mass, serves as the primary capsid protein of ASFV. It is a crucial antigen for the development of ASF subunit vaccines and serological diagnostic methods. In this investigation, 27 monoclonal antibodies (mAbs) were generated through mouse immunization with the truncated C-terminal p72 protein expressed by Escherichia coli. Among these, six mAbs exhibited binding to the p72 trimer, with their respective recognized epitopes identified as 542VTAHGINLIDKF553, 568GNAIKTP574, and 584FALKPREEY592. All three epitopes were situated within the interval sequences of functional units of the C-terminal jelly-roll barrel of p72. Notably, two epitopes, 568GNAIKTP574 and 584FALKPREEY592, were internal to the p72 trimer, while the epitope 542VTAHGINLIDKF553 was exposed on the surface of the trimer and consistently conserved across all ASFV genotypes. These findings enhance our comprehension of the antigenic function and structure of the p72 protein, facilitating the utilization of p72 in the development of diagnostic techniques for ASFV.

10.
ACS Appl Mater Interfaces ; 15(46): 53273-53282, 2023 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-37936291

RESUMO

Accurate targeting of therapeutic agents to specific tumor tissues, especially via deep tumor penetration, has been an effective strategy in cancer treatments. Here, we described a flexible nanoplatform, pH-responsive zwitterionic acylsulfonamide betaine-functionalized fourth-generation PAMAM dendrimers (G4-AB), which presented multiple advantages for chemo-photothermal therapy, including template synthesis of ultrasmall copper sulfide (CuS) nanoparticles and further encapsulation of doxorubicin (DOX) (G4-AB-DOX/CuS), long-circulating performance by a relatively large size and zwitterionic surface in a physiological environment, combined size shrinkage, and charge conversions via pH-responsive behavior in an acidic tumor microenvironment (TME). Accordingly, high tumor penetration and positive cell uptake for CuS and DOX have been determined, which triggered an excellent combination treatment under near-infrared irradiation in comparison to the monochemotherapy system and irresponsive chemo-photothermal system. Our study represented great promise in constructing multifunctional carriers for the effective delivery of photothermal nanoparticles and drugs in chemo-photothermal therapy.


Assuntos
Dendrímeros , Hipertermia Induzida , Nanopartículas , Neoplasias , Humanos , Dendrímeros/uso terapêutico , Terapia Fototérmica , Doxorrubicina/farmacologia , Doxorrubicina/uso terapêutico , Fototerapia , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Cobre/uso terapêutico , Microambiente Tumoral
11.
J Mater Chem B ; 11(30): 7228-7238, 2023 08 02.
Artigo em Inglês | MEDLINE | ID: mdl-37431576

RESUMO

Antimicrobial hydrogel dressings have received extensive attention for their wide and promising applications in preventing infections associated with wound healing. However, the development of versatile antibacterial hydrogels inevitably leads to complex structures, which restricts their applications. In this work, a multifunctional antibacterial hydrogel based on a reversible diolborate bond crosslinked network was prepared via the interactions between the zwitterionic glycopolymer poly[(2-methacryloyloxyethyl phosphorylcholine)-co-(N,N-dimethylacrylamide)-co-(2-lactobionamidoethyl methacrylamide)] (PMDL) and borax in conjunction with a simple mixing of Ag NPs within 10 s. The obtained PMDL-12%/borax/Ag NP hydrogel displays a rapid self-healing ability and excellent injectability, as well as good adhesiveness to biological tissues and surfaces of various materials. Moreover, the hydrogels exhibit efficient antibacterial activities against Escherichia coli and Staphylococcus aureus, which could prevent bacterial infections in wound care. The multifunctional hydrogel also shows good cytocompatibility and hemocompatibility. Importantly, in vivo wound healing evaluation of a mouse full-thickness skin defect model confirms that the hydrogel effectively accelerates cutaneous regeneration and wound healing by regulating inflammation and promoting collagen deposition. This multifunctional wound dressing hydrogel prepared using a facile strategy has promising application in biomedical areas.


Assuntos
Antibacterianos , Hidrogéis , Animais , Camundongos , Hidrogéis/farmacologia , Antibacterianos/farmacologia , Pele , Bandagens , Modelos Animais de Doenças , Escherichia coli
12.
J Transl Med ; 21(1): 487, 2023 07 20.
Artigo em Inglês | MEDLINE | ID: mdl-37474946

RESUMO

BACKGROUND: Lipid metabolism plays an important role in liver regeneration, but its regulation still requires further research. In this study, lipid metabolites involved in mouse liver regeneration at different time points were sequenced and analyzed to study their influence on liver regeneration and its mechanism. METHODS: Our experiment was divided into two parts. The first part examined lipid metabolites during liver regeneration in mice. In this part, lipid metabolites were sequentially analyzed in the livers of 70% mouse hepatectomy models at 0, 1, 3and 7 days after operation to find the changes of lipid metabolites in the process of liver regeneration. We screened L-carnitine as our research object through metabolite detection. Therefore, in the second part, we analyzed the effects of carnitine on mouse liver regeneration and lipid metabolism during liver regeneration. We divided the mouse into four groups: control group (70% hepatectomy group); L-carnitine group (before operation) (L-carnitine were given before operation); L-carnitine group (after operation)(L-carnitine were given after operation) and L-carnitine + perhexiline maleate (before operation) group. Weighing was performed at 24 h, 36 and 48 h in each group, and oil red staining, HE staining and MPO staining were performed. Tunnel fluorescence staining, Ki67 staining and serological examination. RESULTS: Sequencing analysis of lipid metabolites in 70% of mouse livers at different time points after hepatectomy showed significant changes in carnitine metabolites. The results showed that, compared with the control group the mouse in L-carnitine group (before operation) at 3 time points, the number of fat drops in oil red staining was decreased, the number of Ki67 positive cells was increased, the number of MPO positive cells was decreased, the number of Tunnel fluorescence positive cells was decreased, and the liver weight was increased. Serum enzymes were decreased. Compared with control group, L-carnitine group (after operation) showed similar trends in all indexes at 36 and 48 h as L-carnitine group (before operation). L-carnitine + perhexiline maleate (before operation) group compared with control group, the number of fat drops increased, the number of Ki67 positive cells decreased, and the number of MPO positive cells increased at 3 time points. The number of Tunnel fluorescent positive cells increased and serum enzyme increased. However, both liver weights increased. CONCLUSION: L-carnitine can promote liver cell regeneration by promoting lipid metabolism and reduce aseptic inflammation caused by excessive lipid accumulation.


Assuntos
Hepatectomia , Regeneração Hepática , Camundongos , Animais , Regeneração Hepática/fisiologia , Metabolismo dos Lipídeos , Carnitina/farmacologia , Carnitina/metabolismo , Antígeno Ki-67/metabolismo , Fígado/metabolismo , Lipídeos
13.
Mikrochim Acta ; 190(6): 248, 2023 06 02.
Artigo em Inglês | MEDLINE | ID: mdl-37266700

RESUMO

The modification of EGFR aptamer (Apt 1) and HER2 aptamer (Apt 2) with gold nanoparticles (AuNPs) is reported to obtain probe I (Apt 1-AuNPs) and probe II (Apt 2-AuNPs). Taking Eca109, KYSE510, and KYSE150 cells as models, the sandwich scattering system of probe I-cell-probe II was formed by the recognition of tumor markers by the aptamer modified probe, and the resonance Rayleigh scattering (RRS) spectra were investigated. The results showed that the scattering system can be used to quantitatively detect the Eca109 cell lines in the range 5.0×10 to 5.0×105 cells·mL-1 with a detection limit of 15 cells· mL-1.The system can also detect the KYSE510 cell lines in a linear range of 5.0×10 to 5.0×105 cells·mL-1 with a detection limit of 18 cells·mL-1 and the KYSE150 cell lines in a linear range of 3.0×10 to 5.0×105 cells·mL-1 with a detection limit of 12 cells·mL-1. To demonstrate the potential application of the RRS method for real sample analysis, cells were spiked into blank serum samples at concentrations from 1.0×102 to 1.0×105 cells·mL-1. The recovery was between 97.0% and 102.3%, and the RSD was between 1.1% and 4.9%, confirming the feasibility of the proposed method for ESCC cell determination.


Assuntos
Aptâmeros de Nucleotídeos , Neoplasias Esofágicas , Nanopartículas Metálicas , Humanos , Ouro , Neoplasias Esofágicas/diagnóstico
14.
Nat Commun ; 14(1): 3598, 2023 06 16.
Artigo em Inglês | MEDLINE | ID: mdl-37328460

RESUMO

Towards intracellular engineering of living organisms, the development of new biocompatible polymerization system applicable for an intrinsically non-natural macromolecules synthesis for modulating living organism function/behavior is a key step. Herein, we find that the tyrosine residues in the cofactor-free proteins can be employed to mediate controlled radical polymerization under 405 nm light. A proton-coupled electron transfer (PCET) mechanism between the excited-state TyrOH* residue in proteins and the monomer or the chain transfer agent is confirmed. By using Tyr-containing proteins, a wide range of well-defined polymers are successfully generated. Especially, the developed photopolymerization system shows good biocompatibility, which can achieve in-situ extracellular polymerization from the surface of yeast cells for agglutination/anti-agglutination functional manipulation or intracellular polymerization inside yeast cells, respectively. Besides providing a universal aqueous photopolymerization system, this study should contribute a new way to generate various non-natural polymers in vitro or in vivo to engineer living organism functions and behaviours.


Assuntos
Saccharomyces cerevisiae , Tirosina , Tirosina/química , Transporte de Elétrons , Prótons , Polímeros/química , Polimerização
15.
Int J Biol Macromol ; 246: 125567, 2023 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-37379940

RESUMO

In this study, the composite cling film was prepared by solution casting method using chitosan and golden mushroom foot polysaccharide as substrates, and the structure and physicochemical indexes of the composite cling film were characterized by Fourier infrared spectroscopy, X-ray diffraction, and scanning electron microscopy. The results showed that compared with single chitosan film, the composite cling film has better mechanical properties and antioxidant properties, and the barrier of UV light and water vapor is also stronger. Due to its high nutritional value, blueberry has a short shelf life due to its thin skin and poor storage resistance. Therefore, in this study, blueberry was used as the object of freshness preservation, and the single chitosan film group and the uncovered group were used as controls, and the weight loss, total bacterial colony, decay rate, respiration intensity, malondialdehyde content, hardness, soluble solids, titratable acid, anthocyanin content, and VC content of blueberry were used as freshness preservation indexes for experiments. The comprehensive results showed that the freshness preservation effect of the composite film group was significantly higher than that of the control group, with better antibacterial properties, antioxidant properties, etc., which could effectively delay fruit decay and deterioration, thus prolonging the shelf life, and thus the chitosan/Enoki mushroom foot polysaccharide composite preservation film has a high potential as a new freshness preservation material for blueberry.


Assuntos
Agaricales , Mirtilos Azuis (Planta) , Quitosana , Flammulina , Quitosana/química , Embalagem de Alimentos/métodos , Antioxidantes/farmacologia
16.
Environ Toxicol Pharmacol ; 100: 104136, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37127111

RESUMO

Microplastics (MPs) are a hot environmental contaminant now. However, researchers paid little attention to their effects on immune organs such as the thymus. Here, we exposed chickens to a concentration gradient of polystyrene microplastics (PS-MPs) and then followed the decrease in the thymus index. HE staining showed cellular infiltration in the thymus. The assay kit corroborated that PS-MPs impelled oxidative stress in the thymus: increased MDA levels, downregulated antioxidants such as SOD, CAT, and GSH, and significantly undermined total antioxidant capacity. Western blotting and qRT-PCR results showed that Nrf2/NF-κB, Bcl-2/Bax, and AKT signaling pathways were activated in the thymus after exposure to PS-MPs. It stimulated the increased expression of downstream such as IL-1ß, caspase-3, and Beclin1, triggering thymus inflammation, apoptosis, and autophagy. This study provides new insights into the field of microplastic immunotoxicity and highlights potential environmental hazards in poultry farming.


Assuntos
Microplásticos , NF-kappa B , Animais , NF-kappa B/metabolismo , Microplásticos/toxicidade , Plásticos , Poliestirenos/toxicidade , Galinhas , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Antioxidantes/metabolismo , Estresse Oxidativo , Apoptose
17.
Front Vet Sci ; 10: 1175701, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37215478

RESUMO

African swine fever is a highly lethal contagious disease of pigs for which there is no vaccine. Its causative agent African swine fever virus (ASFV) is a highly complex enveloped DNA virus encoding more than 150 open reading frames. The antigenicity of ASFV is still unclear at present. In this study, 35 proteins of ASFV were expressed by Escherichia coli, and ELISA was developed for the detection of antibodies against these proteins. p30, p54, and p22 were presented as the major antigens of ASFV, positively reacting with all five clinical ASFV-positive pig sera, and 10 pig sera experimentally infected by ASFV. Five proteins (pB475L, pC129R, pE199L, pE184L, and pK145R) reacted well with ASFV-positive sera. The p30 induced a rapid and strong antibody immune response during ASFV infection. These results will promote the development of subunit vaccines and serum diagnostic methods against ASFV.

18.
Cell Death Discov ; 9(1): 128, 2023 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-37061523

RESUMO

Prostate cancer is a major disease that threatens men's health. Its rapid progression, easy metastasis, and late castration resistance have brought obstacles to treatment. It is necessary to find new effective anticancer methods. Ferroptosis is a novel iron-dependent programmed cell death that plays a role in various cancers. Understanding how ferroptosis is regulated in prostate cancer will help us to use it as a new way to kill cancer cells. In this review, we summarize the regulation and role of ferroptosis in prostate cancer and the relationship with AR from the perspective of metabolism and molecular pathways. We also discuss the feasibility of ferroptosis in prostate cancer treatment and describe current limitations and prospects, providing a reference for future research and clinical application of ferroptosis.

19.
J Cell Mol Med ; 27(10): 1384-1397, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-37005492

RESUMO

Human placental mesenchymal stem cells (PMSCs) can prevent liver ischaemia-reperfusion injury (LIRI). However, their therapeutic effects are limited. Therefore, additional research is required to elucidate the mechanisms of PMSC-mediated LIRI prevention and enhance the related therapeutic effects. This study aimed to examine the role of the Lin28 protein in the regulation of glucose metabolism in PMSCs. Further, it explored whether Lin28 could enhance the protective effects of PMSCs against LIRI and investigated the underlying mechanisms. Western blotting was performed to examine Lin28 expression in PMSCs under hypoxic conditions. A Lin28 overexpression construct was introduced into PMSCs, and the effect on glucose metabolism was examined using a glucose metabolism kit. Further, the expression of some proteins involved in glucose metabolism and the PI3K-AKT pathway and the levels of microRNA Let-7a-g were examined using western blots and real-time quantitative PCR, respectively. To examine the relationship between Lin28 and the PI3K-Akt pathway, the effects of AKT inhibitor treatment on the changes induced by Lin28 overexpression were examined. Subsequently, AML12 cells were co-cultured with PMSCs to elucidate the mechanisms via which PMSCs prevent hypoxic injury in liver cells in vitro. Finally, C57BL/6J mice were used to establish a partial warm ischaemia-reperfusion model. The mice received intravenous injections containing PMSCs (control and Lin28-overexpressing PMSCs). Finally, their serum transaminase levels and degree of liver injury were assessed using biochemical and histopathological methods, respectively. Lin28 was upregulated under hypoxic conditions in PMSCs. Lin28 exerted protective effects against hypoxia-induced cell proliferation. Moreover, it increased the glycolytic capacity of PMSCs, allowing PMSCs to produce more energy under hypoxic conditions. Lin28 also activated the PI3K-Akt signalling pathway under hypoxic conditions, and its effects were attenuated by AKT inhibition. Lin28 overexpression could protect cells against LIRI-induced liver damage, inflammation and apoptosis and could also attenuate hypoxia-induced hepatocyte injury. Lin28 enhances glucose metabolism under hypoxic conditions in PMSCs, thereby exerting protective effects against LIRI by activating the PI3K-Akt signalling pathway. Our study is the first to report the potential of genetically modified PMSCs for LIRI treatment.


Assuntos
Hepatopatias , Traumatismo por Reperfusão , Animais , Feminino , Humanos , Camundongos , Gravidez , Apoptose/genética , Glucose/farmacologia , Hipóxia , Camundongos Endogâmicos C57BL , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Placenta/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Traumatismo por Reperfusão/genética , Traumatismo por Reperfusão/prevenção & controle , Traumatismo por Reperfusão/metabolismo
20.
Curr Med Sci ; 43(2): 329-335, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37009959

RESUMO

OBJECTIVE: We aimed to identify new, more accurate risk factors of liver transplantation for liver cancer through using the Surveillance, Epidemiology, and End Results (SEER) database. METHODS: Using the SEER database, we identified patients that had undergone surgical resection for non-metastatic hepatocellular carcinoma (HCC) and subsequent liver transplantation between 2010 and 2017. Overall survival (OS) was estimated using Kaplan-Meier plotter. Cox proportional hazards regression modelling was used to identify factors independently associated with recurrent disease [presented as adjusted hazard ratios (HR) with 95% CIs]. RESULTS: Totally, 1530 eligible patients were included in the analysis. There were significant differences in ethnicity (P=0.04), cancer stage (P<0.001), vascular invasion (P<0.001) and gall bladder involvement (P<0.001) between the groups that survived, died due to cancer, or died due to other causes. In the Cox regression model, there were no significant differences in OS at 5 years with different operative strategies (autotransplantation versus allotransplantation), nor at survival at 1 year with neoadjuvant radiotherapy. However, neoadjuvant radiotherapy did appear to improve survival at both 3 years (HR: 0.540, 95% CI: 0.326-0.896, P=0.017) and 5 years (HR: 0.338, 95% CI: 0.153-0.747, P=0.007) from diagnosis. CONCLUSION: This study demonstrated differences in patient characteristics between prognostic groups after liver resection and transplantation for HCC. These criteria can be used to inform patient selection and consent in this setting. Preoperative radiotherapy may improve long-term survival post-transplantation.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Transplante de Fígado , Humanos , Carcinoma Hepatocelular/epidemiologia , Carcinoma Hepatocelular/cirurgia , Neoplasias Hepáticas/patologia , Prognóstico , Modelos de Riscos Proporcionais
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