Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 2.319
Filtrar
1.
J Ethnopharmacol ; 336: 118751, 2025 Jan 10.
Artículo en Inglés | MEDLINE | ID: mdl-39214192

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Huachansu Capsule (HCSc) is a simple enteric-coated capsule refined from the skin of the dried toad, a traditional medicinal herb. It has been used clinically for many years to treat a variety of malignant tumors with remarkable efficacy. To date, a number of main components of HCSc have been reported to be cardiotoxic, but the specific mechanism of cardiotoxicity is still unknown. AIM OF THE STUDY: The aim of this study was to elucidate the possible cardiotoxic symptoms caused by high-doses of HCSc and to further reveal the complex mechanisms by which it causes cardiotoxicity. MATERIALS AND METHODS: UPLC-Q-Exactive Orbitrap MS and network toxicology were used to identify and predict the potential toxic components, related signaling pathways. Then, we used acute and sub-acute toxicity experiments to reveal the apparent phenomenon of HCSc-induced cardiotoxicity. Finally, we combined transcriptomics and metabolomics to elucidate the potential mechanism of action, and verified the putative mechanism by molecular docking, RT-qPCR, and Western blot. RESULTS: We found 8 toad bufadienolides components may be induced cardiac toxicity HCSc main toxic components. Through toxicity experiments, we found that high dose of HCSc could increase a variety of blood routine indexes, five cardiac enzymes, heart failure indexes (BNP), troponin (cTnI and cTnT), heart rate and the degree of heart tissue damage, while low-dose of HCSc had no such changes. In addition, by molecular docking, found that 8 kinds of main toxic components and cAMP, AMPK, IL1ß, mTOR all can be a very good combination, especially in the cAMP. Meanwhile, RT-qPCR and Western blot results showed that HCSc could induce cardiotoxicity by regulating a variety of heart-related differential genes and activating the cAMP signaling pathway. CONCLUSIONS: In this study, network toxicology, transcriptomics and metabolomics were used to elucidate the complex mechanism of possible cardiotoxicity induced by high-dose HCSc. Animal experiments, molecular docking, Western blot and RT-qPCR experiments were also used to verify the above mechanism. These findings will inform further mechanistic studies and provide theoretical support for its safe clinical application.


Asunto(s)
Cardiotoxicidad , Metabolómica , Transcriptoma , Animales , Metabolómica/métodos , Masculino , Transcriptoma/efectos de los fármacos , Ratas , Bufanólidos/toxicidad , Simulación del Acoplamiento Molecular , Ratas Sprague-Dawley , Farmacología en Red , Cápsulas , Transducción de Señal/efectos de los fármacos , Perfilación de la Expresión Génica/métodos , Anuros
2.
Front Immunol ; 15: 1455899, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39308854

RESUMEN

Background: Severe burns can lead to systemic inflammatory response syndrome (SIRS) and multiple organ dysfunction syndrome (MODS) due to inflammation-immunity dysregulation. This study aimed to identify key immune-related molecules and potential drugs for immune regulation in severe burn treatment. Method: Microarray datasets GSE77791 and GSE37069 were analyzed to identify immune-related differentially expressed genes (DEGs), enriched pathways and prognosis-related genes. The DGIdb database was used to identify potentially clinically relevant small molecular drugs for hub DEGs. Hub DEGs were validated by total RNA from clinical blood samples through qPCR. The efficacy of drug candidates was tested in a severe burn mouse model. Pathologic staining was used to observe organ damage. Enzyme Linked Immunosorbent Assay (ELISA) was used to detect the serum IL-1b, IL-6, TNF-a and MCP-1 contents. Activation of the NF-κB inflammatory pathway was detected by western blotting. Transcriptome sequencing was used to observe inflammatory-immune responses in the lung. Results: A total of 113 immune-related DEGs were identified, and the presence of immune overactivation was confirmed in severe burns. S100A8 was not only significantly upregulated and identified to be prognosis-related among the hub DEGs but also exhibited an increasing trend in clinical blood samples. Methotrexate, which targets S100A8, as predicted by the DGIdb, significantly reduces transcription level of S100A8 and inflammatory cytokine content in blood, organ damage (lungs, liver, spleen, and kidneys) and mortality in severely burned mice when combined with fluid resuscitation. The inflammatory-immune response was suppressed in the lungs. Conclusion: S100A8 with high transcription level in blood is a potential biomarker for poor severe burn prognosis. It suggested that methotrexate has a potential application in severe burn immunotherapy. Besides, it should be emphasized that fluid resuscitation is necessary for the function of methotrexate.


Asunto(s)
Quemaduras , Quemaduras/inmunología , Animales , Ratones , Humanos , Pronóstico , Masculino , Perfilación de la Expresión Génica , Modelos Animales de Enfermedad , Metotrexato/uso terapéutico , Citocinas/metabolismo , Citocinas/sangre , Biología Computacional/métodos , Transcriptoma , Ratones Endogámicos C57BL , Femenino , Biomarcadores
3.
Food Chem ; 463(Pt 3): 141352, 2024 Sep 19.
Artículo en Inglés | MEDLINE | ID: mdl-39316903

RESUMEN

In this study, we investigated the protein structures, powder characteristics, as well as rehydration and emulsifying properties of spray-dried egg yolk powder after short-time lactic acid fermentation (3.5 h). Results indicate that fermentation improved the rehydration and emulsifying properties of yolk powder. Limosilactobacillus reuteri-fermented yolk powder exhibited better wettability due to the porous structure of particles and higher hydrophilicity. Lacticaseibacillus rhamnosus-fermented yolk powder had an enhanced coefficient of stability due to its smaller particles and higher surface charge. The higher water solubility of fermented yolk powder samples is mainly attributed to their lower hydrophobicity and higher zeta potential. The enhanced emulsifying activity of fermented yolk powder samples is primarily related to their increased ß-turn structure and better solubility. Furthermore, fermentation treatment altered powder moisture content and bulk densities, while not affecting its flow behavior and thermal stability. This study provides an effective approach to improving the quality of yolk powder.

4.
Food Funct ; 2024 Sep 25.
Artículo en Inglés | MEDLINE | ID: mdl-39319490

RESUMEN

Correction for 'Grifola frondosa polysaccharides ameliorate lipid metabolic disorders and gut microbiota dysbiosis in high-fat diet fed rats' by Lu Li et al., Food Funct., 2019, 10, 2560-2572, https://doi.org/10.1039/C9FO00075E.

5.
J Transl Med ; 22(1): 860, 2024 Sep 27.
Artículo en Inglés | MEDLINE | ID: mdl-39334418

RESUMEN

BACKGROUND: There is currently a lack of comprehensive evidence regarding the correlation between Alternate Mediterranean Diet (AMED) and the survival of patients with ovarian cancer (OC). This prospective cohort study first assessed the association of AMED, not only pre-diagnosis and post-diagnosis but also the change from pre-diagnosis to post-diagnosis with OC survival. METHODS: A total of 560 OC patients were included in the study, and their dietary intake was assessed using a reliable 111-item food frequency questionnaire. The overall survival (OS) of the patients was monitored through active follow-up and review of medical records until February 16th, 2023. Cox proportional hazard regression models were utilized to compute the hazard ratios (HRs) and their corresponding 95% confidence intervals (CIs). RESULTS: Out of the total 560 patients with OC, 211 (37.68%) succumbed during a median follow-up period of 44.40 months (interquartile range: 26.97-61.37). Comparative analysis indicated a significant association between the highest tertiles of pre-diagnosis (HR = 0.59; 95% CI 0.38-0.90; Ptrend < 0.05) and post-diagnosis (HR = 0.61; 95% CI 0.41-0.91; Ptrend < 0.05) AMED intake and improved OS as opposed to the lowest tertile. Additionally, a significant linear trend was observed for AMED and OC survival. Notably, decreased intake (more than 5% change) and significantly increased intake (more than 15% change) of AMED from pre-diagnosis to post-diagnosis were linked to worse and better OS, respectively, when compared to the stable intake group (change within 5%). Furthermore, patients displaying consistently higher AMED intake both before and after diagnosis experienced enhanced OS in comparison to those with consistently low AMED intake (HRHigh-High vs. Low-Low = 0.47; 95% CI 0.31-0.70). CONCLUSION: High pre-diagnosis and post-diagnosis AMED was associated with an improved OS in patients with OC, suggesting that maintaining a consistently high intake of AMED could potentially benefit the prognosis of OC.


Asunto(s)
Dieta Mediterránea , Neoplasias Ováricas , Humanos , Femenino , Neoplasias Ováricas/diagnóstico , Neoplasias Ováricas/mortalidad , Neoplasias Ováricas/dietoterapia , Estudios Prospectivos , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Análisis de Supervivencia , Adulto , Estimación de Kaplan-Meier , Anciano
6.
Cell Biol Toxicol ; 40(1): 82, 2024 Sep 25.
Artículo en Inglés | MEDLINE | ID: mdl-39320524

RESUMEN

Angiotensin-converting enzyme 2 (ACE2), a crucial element of the renin-angiotensin system (RAS), metabolizes angiotensin II into Ang (1-7), which then combines with the Mas receptor (MasR) to fulfill its protective role in various diseases. Nevertheless, the involvement of ACE2 in sepsis-induced cardiomyopathy (SIC) is still unexplored. In this study, our results revealed that CLP surgery dramatically impaired cardiac function accompanied with disruption of the balance between ACE2-Ang (1-7) and ACE-Ang II axis in septic heart tissues. Moreover, ACE2 knockin markedly alleviated sepsis induced RAS disorder, cardiac dysfunction and improved survival rate in mice, while ACE2 knockout significantly exacerbates these outcomes. Adoptive transfer of bone marrow cells and in vitro experiments showed the positive role of myeloid ACE2 by mitigating oxidative stress, inflammatory response, macrophage polarization and cardiomyocyte apoptosis by blocking NF-κB and STAT1 signals. However, the beneficial impacts were nullified by MasR antagonist A779. Collectively, these findings showed that ACE2 alleviated SIC by inhibiting M1 macrophage via activating the Ang (1-7)-MasR axis, highlight that ACE2 might be a promising target for the management of sepsis and SIC patients.


Asunto(s)
Enzima Convertidora de Angiotensina 2 , Cardiomiopatías , Macrófagos , FN-kappa B , Factor de Transcripción STAT1 , Sepsis , Transducción de Señal , Animales , Enzima Convertidora de Angiotensina 2/metabolismo , Enzima Convertidora de Angiotensina 2/genética , Sepsis/complicaciones , Sepsis/metabolismo , FN-kappa B/metabolismo , Cardiomiopatías/metabolismo , Ratones , Factor de Transcripción STAT1/metabolismo , Macrófagos/metabolismo , Masculino , Ratones Endogámicos C57BL , Ratones Noqueados , Apoptosis/efectos de los fármacos , Sistema Renina-Angiotensina/efectos de los fármacos , Receptores Acoplados a Proteínas G/metabolismo , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/efectos de los fármacos , Miocitos Cardíacos/patología , Estrés Oxidativo/efectos de los fármacos , Angiotensina I/metabolismo , Angiotensina I/farmacología , Proto-Oncogenes Mas , Fragmentos de Péptidos/metabolismo , Fragmentos de Péptidos/farmacología , Peptidil-Dipeptidasa A/metabolismo , Peptidil-Dipeptidasa A/genética
7.
Plants (Basel) ; 13(18)2024 Sep 16.
Artículo en Inglés | MEDLINE | ID: mdl-39339566

RESUMEN

When a plant is infected by a pathogen, endogenous immune responses are initiated. When the initiation of these defense responses is induced by a pathogen-associated molecular pattern (PAMP) of a pathogen, it is called PAMP-triggered immunity (PTI). Previous studies have shown that Bacillus amyloliquefaciens PMB05 can enhance PTI signals and improve disease control of bacterial soft rot and wilt in Arabidopsis thaliana. In the context of controlling bacterial wilt disease, the involvement of a mitogen-activated protein kinase (MAPK) signaling pathway has been established. Nevertheless, it remains unclear whether this pathway is also required for B. amyloliquefaciens PMB05 in controlling bacterial soft rot. In this study, A. thaliana ecotype Columbia (Col-0) and its mutants on a MAPK pathway-related pathway were used as a model and established that the ability of B. amyloliquefaciens PMB05 to control soft rot requires the participation of the MAPK pathway. Moreover, the enhancement of disease resistance by PMB05 is highly correlated with the activation of reactive oxygen species generation and stomata closure, rather than callose deposition. The spray inoculation method was used to illustrate that PMB05 can enhance stomatal closure, thereby restricting invasion by the soft rot bacterium. This control mechanism has also been demonstrated to require the activation of the MAPK pathway. This study demonstrates that B. amyloliquefaciens PMB05 can accelerate stomata closure via the activation of the MAPK pathway during PTI, thereby reducing pathogen invasion and achieving disease resistance against bacterial soft rot.

8.
Cureus ; 16(8): e66231, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39238702

RESUMEN

Neurocysticercosis (NCC) is a central nervous system infection caused by Taenia solium or pork tapeworm. It affects millions worldwide and represents a leading cause of epilepsy in developing countries. NCC may be challenging to distinguish from intracranial tuberculomas, with tuberculosis being highly prevalent in developing countries. We highlight the importance of clinical history, including exposure history and neuroimaging, in obtaining an accurate diagnosis to enable prompt treatment. This report presents the case of a 26-year-old man diagnosed with NCC and presenting with acute giddiness and headache. Otherwise, there was no history of fever or constitutional symptoms. Neuroimaging demonstrated multiple cerebral lesions over both hemispheres, with degenerating scolex on brain MRI. He recovered well following a combination of oral albendazole, praziquantel, and corticosteroids. This case highlights the salient features that distinguish NCC from intracranial tuberculoma. Early and precise diagnosis will ensure that patients receive optimal treatment, expedite recovery, and prevent further complications.

9.
J Med Internet Res ; 26: e63367, 2024 Sep 20.
Artículo en Inglés | MEDLINE | ID: mdl-39238480

RESUMEN

BACKGROUND: As the global population ages, we witness a broad scientific and technological revolution tailored to meet the health challenges of older adults. Over the past 25 years, technological innovations, ranging from advanced medical devices to user-friendly mobile apps, are transforming the way we address these challenges, offering new avenues to enhance the quality of life and well-being of the aging demographic. OBJECTIVE: This study aimed to systematically review the development trends in technology for managing and caring for the health of older adults over the past 25 years and to project future development prospects. METHODS: We conducted a comprehensive bibliometric analysis of literatures related to technology-based solutions for health challenges in aging, published up to March 18, 2024. The search was performed using the Web of Science Core Collection, covering a span from 1999 to 2024. Our search strategy was designed to capture a broad spectrum of terms associated with aging, health challenges specific to older adults, and technological interventions. RESULTS: A total of 1133 publications were found in the Web of Science Core Collection. The publication trend over these 25 years showed a gradual but fluctuating increase. The United States was the most productive country and participated in international collaboration most frequently. The predominant keywords identified through this analysis included "dementia," "telemedicine," "older-adults," "telehealth," and "care." The keywords with citation bursts included "telemedicine" and "digital health." CONCLUSIONS: The scientific and technological revolution has significantly improved older adult health management, particularly in chronic disease monitoring, mobility, and social connectivity. The momentum for innovation continues to build, with future research likely to focus on predictive analytics and personalized health care solutions, further enhancing older adults' independence and quality of life.


Asunto(s)
Envejecimiento , Bibliometría , Humanos , Anciano , Calidad de Vida , Telemedicina/tendencias , Telemedicina/estadística & datos numéricos
10.
Int J Mol Sci ; 25(17)2024 Aug 23.
Artículo en Inglés | MEDLINE | ID: mdl-39273087

RESUMEN

Activating enhancer-binding protein 2 (AP-2) is a family of transcription factors (TFs) that play crucial roles in regulating embryonic and oncogenic development. In addition to splice isoforms, five major family members encoded by the TFAP2A/B/C/D/E genes have been identified in humans, i.e., AP-2α/ß/γ/δ/ε. In general, the first three TFs have been studied more thoroughly than AP-2δ or AP-2ε. Currently, there is a relatively limited body of literature focusing on the AP-2 family in the context of gastroenterological research, and a comprehensive overview of the existing knowledge and recommendations for further research directions is lacking. Herein, we have collected available gastroenterological data on AP-2 TFs, discussed the latest medical applications of each family member, and proposed potential future directions. Research on AP-2 in gastrointestinal tumors has predominantly been focused on the two best-described family members, AP-2α and AP-2γ. Surprisingly, research in the past decade has highlighted the importance of AP-2ε in the drug resistance of gastric cancer (GC) and colorectal cancer (CRC). While numerous questions about gastroenterological disorders await elucidation, the available data undoubtedly open avenues for anti-cancer targeted therapy and overcoming chemotherapy resistance. In addition to gastrointestinal cancers, AP-2 family members (primarily AP-2ß and marginally AP-2γ) have been associated with other health issues such as obesity, type 2 diabetes, liver dysfunction, and pseudo-obstruction. On the other hand, AP-2δ has been poorly investigated in gastroenterological disorders, necessitating further research to delineate its role. In conclusion, despite the limited attention given to AP-2 in gastroenterology research, pivotal functions of these transcription factors have started to emerge and warrant further exploration in the future.


Asunto(s)
Factor de Transcripción AP-2 , Humanos , Factor de Transcripción AP-2/metabolismo , Factor de Transcripción AP-2/genética , Enfermedades Gastrointestinales/genética , Enfermedades Gastrointestinales/metabolismo , Animales
11.
J Clin Invest ; 134(18)2024 Aug 06.
Artículo en Inglés | MEDLINE | ID: mdl-39286985

RESUMEN

BACKGROUNDFrailty significantly affects morbidity and mortality rates in the older population (age >65 years). Age-related degenerative diseases are influenced by the intestinal microbiota. However, limited research exists on alterations in the intestinal microbiota in frail older individuals, and the effectiveness of prebiotic intervention for treating frailty remains uncertain.OBJECTIVEWe sought to examine the biological characteristics of the intestinal microbiome in frail older individuals and assess changes in both frailty status and gut microbiota following intervention with a prebiotic blend consisting of inulin and oligofructose.METHODSThe study consisted of 3 components: an observational analysis with a sample size of 1,693, a cross-sectional analysis (n = 300), and a multicenter double-blind, randomized, placebo-controlled trial (n = 200). Body composition, commonly used scales, biochemical markers, intestinal microbiota, and metabolites were examined in 3 groups of older individuals (nonfrail, prefrail, and frail). Subsequently, changes in these indicators were reevaluated after a 3-month intervention using the prebiotic mixture for the prefrail and frail groups.RESULTSThe intervention utilizing a combination of prebiotics significantly improved frailty and renal function among the older population, leading to notable increases in protein levels, body fat percentage, walking speed, and grip strength. Additionally, it stimulated an elevation in gut probiotic count and induced alterations in microbial metabolite expression levels as well as corresponding metabolic pathways.CONCLUSIONSThe findings suggest a potential link between changes in the gut microbiota and frailty in older adults. Prebiotics have the potential to modify the gut microbiota and metabolome, resulting in improved frailty status and prevention of its occurrence.TRIAL REGISTRATIONClinicalTrials.gov NCT03995342.


Asunto(s)
Anciano Frágil , Fragilidad , Microbioma Gastrointestinal , Prebióticos , Humanos , Prebióticos/administración & dosificación , Anciano , Masculino , Método Doble Ciego , Femenino , Anciano de 80 o más Años , Vida Independiente , Oligosacáridos/administración & dosificación , Inulina/administración & dosificación , Estudios Transversales
12.
Sci Total Environ ; 954: 176351, 2024 Sep 17.
Artículo en Inglés | MEDLINE | ID: mdl-39299314

RESUMEN

Phthalates (PAEs), especially di (2-ethylhexyl) phthalate (DEHP), are generally considered to have adverse impact on nervous system. The residue of DEHP in the environment has gradually become a widely concerned environmental problem due to its widespread use in plastic items. Lycopene (LYC) as the readily available natural antioxidant is considered to have the potential to alleviate exogenous poisons-induced nerve damage. However, there is currently a lack of strategies to alleviate the neurotoxicity caused by DEHP, and it is also unknown whether LYC can alleviate the neurotoxicity caused by DEHP. The experiment demonstrated that LYC had the potential to mitigate DEHP-induced mitochondrial damage in cerebellum. DEHP induced the disorder of Ca2+ transport in cerebellum, thereby resulting in the imbalance of protein homeostasis. Such disruption in protein homeostasis further results in the overactivation of mitochondrial unfolded protein response (UPRmt) and mitochondrial injury. Mechanistically, LYC could alleviate the imbalance of calcium homeostasis and protein homeostasis induced by DEHP via regulating inositol 1, 4, 5-trisphosphate receptor type1 (IP3R1) and sarco/endoplasmic reticulum Ca (2+)-ATPase 2 (SERCA2), further alleviating mitochondrial damage in cerebellum. Subsequently, the present study suggested the mechanism of cerebellar injury induced by DEHP, and provided a novel approach to treating DEHP-induced neurotoxicity.

13.
EMBO J ; 2024 Sep 27.
Artículo en Inglés | MEDLINE | ID: mdl-39333773

RESUMEN

Inherited deficiency of zinc finger NFX1-type containing 1 (ZNFX1), a dsRNA virus sensor, is associated with severe familial immunodeficiency, multisystem inflammatory disease, increased susceptibility to viruses, and early mortality. However, limited treatments for patients with pathological variants of ZNFX1 exist due to an incomplete understanding of the diseases resulting from ZNFX1 mutations. Here, we demonstrate that ZNFX1 specifically inhibits the activation of the NLR family pyrin domain-containing protein 3 (NLRP3) inflammasome in response to NLRP3 activators both in vitro and in vivo. ZNFX1 retains NLRP3 in the cytoplasm and prevents its accumulation in the TGN38 + /TGN46+ vesicles in the resting state. Upon NLRP3 inflammasome activation, ZNFX1 is cleaved by caspase-1, establishing a feed-forward loop that promotes NLRP3 accumulation in the trans-Golgi network (TGN) and amplifies the activity of the downstream cascade. Expression of wild-type ZNFX1, but not of ZNFX1 with human pathogenic mutations, rescues the impairment of NLRP3 inflammasome inhibition. Our findings reveal a dual role of ZNFX1 in virus sensing and suppression of inflammation, which may become valuable for the development of treatments for ZNFX1 mutation-related diseases.

14.
J Am Chem Soc ; 2024 Sep 25.
Artículo en Inglés | MEDLINE | ID: mdl-39321390

RESUMEN

The selective construction of bridged bicyclic scaffolds has garnered increasing attention because of their extensive use as saturated bioisosteres of arene in pharmaceutical industry. However, in sharp contrast to their racemic counterparts, assembling chiral bridged bicyclic structures in an enantioselective and regioselective manner remains challenging. Herein, we describe our protocol for constructing chiral 2-oxa-3-azabicyclo[3.1.1]heptanes (BCHeps) by enantioselective [4π + 2σ] cycloadditions of bicyclo[1.1.0]butanes (BCBs) and nitrones taking advantage of a chiral copper(II) complex as a Lewis acid catalyst. This method features mild conditions, good functional group tolerance, high yield (up to 99%), and excellent enantioselectivity (up to 99% ee). Density functional theory (DFT) calculation elucidates the origin of the reaction's enantioselectivity and the mechanism of BCB activation by Cu(II) complex.

15.
World J Gastrointest Surg ; 16(8): 2374-2381, 2024 Aug 27.
Artículo en Inglés | MEDLINE | ID: mdl-39220060

RESUMEN

In this editorial, we comment on the article "Analysis of the impact of immunotherapy efficacy and safety in patients with gastric cancer and liver metastasis" by Liu et al that was published in the recent issue of the World Journal of Gastrointestinal Surgery. It has prompted us to think and summarize some thoughts on immunotherapy for malignant tumor liver metastasis. Immunotherapy plays a crucial role in the treatment of malignant tumors; however, the presence of liver metastases in advanced tumors may impact its efficacy. Although patients with liver metastases can still benefit from immunotherapy, multiple clinical studies have indicated that, compared to other sites of metastasis, liver metastases may diminish the effectiveness of immunotherapy. The efficacy of immune checkpoint inhibitors in patients with liver metastases often fails to reach the ideal level, primarily due to the liver metastases exploiting the host's peripheral immune tolerance mechanisms to promote systemic CD8(+) T cell exhaustion, resulting in a systemic immune-tolerant environment. This article aims to summarize the reasons for the decreased efficacy of immunotherapy following liver metastasis in various malignant tumors and propose potential clinical strategies for management.

16.
Acta Pharm Sin B ; 14(8): 3513-3527, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39220861

RESUMEN

Bile acids (BAs) are natural metabolites in mammals and have the potential to function as drugs against viral infection. However, the limited understanding of chenodeoxycholic acid (CDCA) receptors and downstream signaling, along with its lower suppression efficiency in inhibiting virus infection limits its clinical application. In this study, we demonstrate that farnesoid X receptor (FXR), the receptor of CDCA, negatively regulates interferon signaling, thereby contributing to the reduced effectiveness of CDCA against virus replication. FXR deficiency or pharmacological inhibition enhances interferon signaling activation to suppress virus infection. Mechanistically, FXR impairs the DNA binding and transcriptional abilities of activated interferon regulatory factor 3 (IRF3) through interaction. Reduced IRF3 transcriptional activity by FXR-IRF3 interaction significantly undermines the expression of Interferon Beta 1 (IFNB1) and the antiviral response of cells, especially upon the CDCA treatment. In FXR-deficient cells, or when combined with Z-guggulsterone (GUGG) treatment, CDCA exhibits a more potent ability to restrict virus infection. Thus, these findings suggest that FXR serves as a limiting factor for CDCA in inhibiting virus replication, which can be attributed to the "signaling-brake" roles of FXR in interferon signaling. Targeting FXR inhibition represents a promising pharmaceutical strategy for the clinical application of BAs metabolites as antiviral drugs.

17.
Ying Yong Sheng Tai Xue Bao ; 35(7): 1753-1761, 2024 Jul 18.
Artículo en Inglés | MEDLINE | ID: mdl-39233403

RESUMEN

Warming drives material cycling in terrestrial ecosystems by affecting litter decomposition, as it can alter litter yield, quality and decomposer composition and activity. The effect of warming on the decomposition of mixed litter in arid and semi-arid zones remains unknown. We investigated the mass loss and nutrient release dynamics during 450 days of decomposition of Artemisia ordosica, Leymus secalinus, and their mixture in Mu Us Desert by open-top chambers and litter bags. The results showed interspecific differences in the responses to warming, in that warming promoted mass loss and N and P release from L. secalinus and inhibited mass loss and P but promoting N release from A. ordosica. Mixing of A. ordosica and L. secalinus litter inhibited decomposition. Warming enhanced the antagonistic effects of mixed decomposition. The total mass loss of mixed litter was decreased by 9%, and the release of N and P was decreased by 4.9% and 12.6%, respectively. The antagonistic effects of mixed litter mass loss and P release under the warming treatment gradually strengthened with time, with N release changing from a synergistic to an antagonistic effect at 150 d. The non-additive effects produced by the mixed decomposition of A. ordosica and L. secalinus litter were jointly regulated by temperature and time. Future research on mixed litter decomposition should consider the interaction between temperature and time.


Asunto(s)
Artemisia , Clima Desértico , Artemisia/crecimiento & desarrollo , Artemisia/química , China , Poaceae/crecimiento & desarrollo , Hojas de la Planta/química , Hojas de la Planta/metabolismo , Nitrógeno/análisis , Nitrógeno/química , Ecosistema , Fósforo/química , Fósforo/análisis , Factores de Tiempo , Calor , Calentamiento Global
18.
RSC Adv ; 14(39): 28285-28297, 2024 Sep 04.
Artículo en Inglés | MEDLINE | ID: mdl-39239279

RESUMEN

In the current study, NiO nanoparticles, MnO nanoparticles, and Mn2NiO4 nanocomposites (Ni-NPs, Mn-NPs and MN-NCs, respectively) were synthesized using a facile hydrothermal method, and their performance in the removal of amaranth (AM) dye from synthetic wastewater was compared. XRD, FTIR spectroscopy, SEM, BET analysis, and TGA were performed to characterize the produced catalysts. The effect of pertinent parameters, including pH, dosage of catalysts, temperature, and shaking speed on the uptake of AM was investigated through batch experiments. The MN-NCs showed ultrafast and high efficiency for AM removal compared to their counter parts Mn-NPs and Ni-NPs. Under ideal conditions, the highest adsorption efficiencies of AM onto Ni-NPs, Mn-NPs, and MN-NCs were calculated to be 80.50%, 93.85%, and 98.50%, respectively. The Langmuir isotherm fitted the experimental data of AM removal better as shown by the higher values of r 2, compared to the Freundlich isotherm, indicating monolayer type adsorption of AM. According to kinetic analyses, the adsorption of AM was best described by the pseudo-second-order kinetic model. Further, regeneration/recycling studies showed that MN-NCs retained 79% adsorption efficiency after four cycles. DFT experiments were also conducted to gain a deeper understanding of the process and behavior of AM adsorption. In conclusion, as Ni-NPs, Mn-NPs, and MN-NCs adsorb AM predominantly via electrostatic interaction, they can be applied for the removal of both cationic and anionic dyes by controlling the pH factor.

19.
Food Microbiol ; 124: 104620, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-39244356

RESUMEN

The spoilage of irradiated ready-to-eat chicken feet (RTECF) seriously affects the food's quality, resulting in package swelling and off-flavors, both of which are highly undesirable to stakeholders and consumers. To investigate the spoilage characteristics of irradiated RTECF and the microorganisms responsible for the spoilage and swelling, the changes in physicochemical properties, microbial community, and volatile organic compounds (VOCs) between normal and spoiled RTECF were evaluated. Compared with normal samples, the spoiled RTECF showed a higher pH value and total volatile basic nitrogen (TVB-N) value, lower color value, and texture features (P < 0.05). Acinetobacter, Pseudomonas, Lactobacillus, and Candida were the dominant genera responsible for RTECF spoilage as confirmed through both culture-dependent methods and high-throughput sequencing (HTS). The results of the verification for gas-producing strains showed that Lactobacillus brevis could cause RTECF packaging to swell. A total of 20 key VOCs were identified using headspace solid-phase microextraction combined with gas chromatography-mass spectrometry (HS-SPME-GC-MS). The results of Pearson correlation analysis (|r|>0.8, P < 0.05) showed that 12 dominant core microbial genera had a significant effect on the flavor of RTECF before and after spoilage. This study provides a theoretical reference for solving the problem of RTECF spoilage and improving the overall quality of RTECF products.


Asunto(s)
Bacterias , Pollos , Irradiación de Alimentos , Microbiología de Alimentos , Compuestos Orgánicos Volátiles , Pollos/microbiología , Animales , Compuestos Orgánicos Volátiles/análisis , Compuestos Orgánicos Volátiles/química , Compuestos Orgánicos Volátiles/metabolismo , Bacterias/clasificación , Bacterias/efectos de la radiación , Bacterias/aislamiento & purificación , Bacterias/genética , Bacterias/crecimiento & desarrollo , Bacterias/metabolismo , Irradiación de Alimentos/métodos , Microbiota/efectos de la radiación , Embalaje de Alimentos/métodos , Cromatografía de Gases y Espectrometría de Masas , Concentración de Iones de Hidrógeno , Comida Rápida/microbiología , Comida Rápida/análisis
20.
Int J Nanomedicine ; 19: 9273-9289, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39282576

RESUMEN

Subretinal injection (SR injection) is a commonly used method of ocular drug delivery and has been mainly applied for the treatment of neovascular age-associated macular degeneration (nAMD) and sub-macular hemorrhage (SMH) caused by nAMD, as well as various types of hereditary retinopathies (IRD) such as Stargardt's disease (STGD), retinitis pigmentosa (RP), and a series of fundus diseases such as Leber's congenital dark haze (LCA), choroidal defects, etc. The commonly used carriers of SR injection are mainly divided into viral and non-viral vectors. Leber's congenital amaurosis (LCA), choroidal agenesis, and a series of other fundus diseases are also commonly treated using SR injection. The commonly used vectors for SR injection are divided into two categories: viral vectors and non-viral vectors. Viral vectors are a traditional class of SR injection drug carriers that have been extensively studied in clinical treatment, but they still have many limitations that cannot be ignored, such as poor reproduction efficiency, small loading genes, and triggering of immune reactions. With the rapid development of nanotechnology in the treatment of ocular diseases, nanovectors have become a research hotspot in the field of non-viral vectors. Nanocarriers have numerous attractive properties such as low immunogenicity, robust loading capacity, stable structure, and easy modification. These valuable features imply greater safety, improved therapeutic efficacy, longer duration, and more flexible indications. In recent years, there has been a growing interest in nanocarriers, which has led to significant advancements in the treatment of ocular diseases. Nanocarriers have not only successfully addressed clinical problems that viral vectors have failed to overcome but have also introduced new therapeutic possibilities for certain classical disease types. Nanocarriers offer undeniable advantages over viral vectors. This review discusses the advantages of subretinal (SR) injection, the current status of research, and the research hotspots of gene therapy with viral vectors. It focuses on the latest progress of nanocarriers in SR injection and enumerates the limitations and future perspectives of nanocarriers in the treatment of fundus lesions. Furthermore, this review also covers the research progress of nanocarriers in the field of subretinal injection and highlights the value of nanocarrier-mediated SR injection in the treatment of fundus disorders. Overall, it provides a theoretical basis for the application of nanocarriers in SR injection.


Asunto(s)
Portadores de Fármacos , Humanos , Animales , Portadores de Fármacos/química , Inyecciones Intraoculares , Retina , Enfermedades de la Retina/terapia , Enfermedades de la Retina/tratamiento farmacológico , Nanopartículas/química , Sistemas de Liberación de Medicamentos/métodos , Vectores Genéticos/administración & dosificación , Vectores Genéticos/genética , Degeneración Macular/terapia
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA