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1.
Front Plant Sci ; 15: 1359315, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38988632

RESUMEN

The gene encoding 9-cis-epoxycarotenoid dioxygenase 3 (NCED3) functions in abscisic acid (ABA) biosynthesis, plant growth and development, and tolerance to adverse temperatures, drought and saline conditions. In this study, three rice lines were used to explore the function of OsNCED3, these included an OsNCED3-overexpressing line (OsNCED3-OE), a knockdown line (osnced3-RNAi) and wild-type rice (WT). These rice lines were infested with the brown plant hopper (BPH; Nilaparvata lugens) and examined for physiological and biochemical changes, hormone content, and defense gene expression. The results showed that OsNCED3 activated rice defense mechanisms, which led to an increased defense enzyme activity of superoxide dismutase, peroxidase, and polyphenol oxidase. The overexpression of OsNCED3 decreased the number of planthoppers and reduced oviposition and BPH hatching rates. Furthermore, the overexpression of OsNCED3 increased the concentrations of jasmonic acid, jasmonyl-isoleucine and ABA relative to WT rice and the osnced3-RNAi line. These results indicate that OsNCED3 improved the stress tolerance in rice and support a role for both jasmonates and ABA as defense compounds in the rice-BPH interaction.

2.
Opt Lett ; 49(13): 3677, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38950239

RESUMEN

This publisher's note contains a correction to Opt. Lett.48, 3219 (2023)10.1364/OL.486644.

3.
Front Immunol ; 15: 1381778, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38947336

RESUMEN

Background: The interaction between pyroptosis-a form of programmed cell death-and tumor immunity represents a burgeoning field of interest. Pyroptosis exhibits a dual role in cancer: it can both promote tumor development and counteract it by activating immune responses that inhibit tumor evasion and encourage cell death. Current tumor immunotherapy strategies, notably CAR-T cell therapy and immune checkpoint inhibitors (ICIs), alongside the potential of certain traditional Chinese medicinal compounds, highlight the intricate relationship between pyroptosis and cancer immunity. As research delves deeper into pyroptosis mechanisms within tumor therapy, its application in enhancing tumor immune responses emerges as a novel research avenue. Purpose: This review aims to elucidate the mechanisms underlying pyroptosis, its impact on tumor biology, and the advancements in tumor immunotherapy research. Methods: A comprehensive literature review was conducted across PubMed, Embase, CNKI, and Wanfang Database from the inception of the study until August 22, 2023. The search employed keywords such as "pyroptosis", "cancer", "tumor", "mechanism", "immunity", "gasdermin", "ICB", "CAR-T", "PD-1", "PD-L1", "herbal medicine", "botanical medicine", "Chinese medicine", "traditional Chinese medicine", "immunotherapy", linked by AND/OR, to capture the latest findings in pyroptosis and tumor immunotherapy. Results: Pyroptosis is governed by a complex mechanism, with the Gasdermin family playing a pivotal role. While promising for tumor immunotherapy application, research into pyroptosis's effect on tumor immunity is still evolving. Notably, certain traditional Chinese medicine ingredients have been identified as potential pyroptosis inducers, meriting further exploration. Conclusion: This review consolidates current knowledge on pyroptosis's role in tumor immunotherapy. It reveals pyroptosis as a beneficial factor in the immunotherapeutic landscape, suggesting that leveraging pyroptosis for developing novel cancer treatment strategies, including those involving traditional Chinese medicine, represents a forward-looking approach in oncology.


Asunto(s)
Inmunoterapia , Neoplasias , Piroptosis , Piroptosis/inmunología , Piroptosis/efectos de los fármacos , Humanos , Neoplasias/inmunología , Neoplasias/terapia , Neoplasias/tratamiento farmacológico , Inmunoterapia/métodos , Animales , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Inhibidores de Puntos de Control Inmunológico/farmacología , Microambiente Tumoral/inmunología , Microambiente Tumoral/efectos de los fármacos
4.
Front Oncol ; 14: 1384928, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38947884

RESUMEN

Sirtuins are pivotal in orchestrating numerous cellular pathways, critically influencing cell metabolism, DNA repair, aging processes, and oxidative stress. In recent years, the involvement of sirtuins in tumor biology has garnered substantial attention, with a growing body of evidence underscoring their regulatory roles in various aberrant cellular processes within tumor environments. This article delves into the sirtuin family and its biological functions, shedding light on their dual roles-either as promoters or inhibitors-in various cancers including oral, breast, hepatocellular, lung, and gastric cancers. It further explores potential anti-tumor agents targeting sirtuins, unraveling the complex interplay between sirtuins, miRNAs, and chemotherapeutic drugs. The dual roles of sirtuins in cancer biology reflect the complexity of targeting these enzymes but also highlight the immense therapeutic potential. These advancements hold significant promise for enhancing clinical outcomes, marking a pivotal step forward in the ongoing battle against cancer.

5.
Fundam Res ; 4(1): 123-130, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38933834

RESUMEN

The most important optical component in an optical fiber endoscope is its objective lens. To achieve a high imaging performance level, the development of an ultra-compact objective lens is thus the key to an ultra-thin optical fiber endoscope. In this work, we use femtosecond laser 3D printing to develop a series of micro objective lenses with different optical designs. The imaging resolution and field-of-view performances of these printed micro objective lenses are investigated via both simulations and experiments. For the first time, multiple micro objective lenses with different fields of view are printed on the end face of a single imaging optical fiber, thus realizing the perfect integration of an optical fiber and objective lenses. This work demonstrates the considerable potential of femtosecond laser 3D printing in the fabrication of micro-optical systems and provides a reliable solution for the development of an ultrathin fiber endoscope.

6.
Sensors (Basel) ; 24(11)2024 Jun 06.
Artículo en Inglés | MEDLINE | ID: mdl-38894474

RESUMEN

A highly sensitivity balloon-like fiber interferometer based on ethanol coating is presented in this paper. The Mach-Zehnder interferometer is formed by bending a single-mode fiber to a balloon-like structure and nested in the Teflon tube. Then, an ethanol solution was filled into the tube of the balloon-like fiber interferometer by the capillary effect. Due to the high sensitivity of the refractive index (RI) of ethanol solutions to temperature, when the external temperature varies, the optical path difference changes. The change in temperature can be detected by the shift in the interference spectrum. Limited by the size of the balloon-like structure, three kinds of these structures with different sensitive lengths were prepared to select the best parameters. The sensitive lengths were 10, 15 and 20 mm, respectively, and the RI detection performance of each structure in 10~26% NaCl solutions was investigated experimentally. The results show that when the sensitive length is 20 mm, the RI sensitivity of the sensor is the highest, which is 212.88 nm/RIU. Ultimately, the sensitive length filled with ethanol is 20 mm. The experimental results show that the temperature sensitivity of the structure is 1.145 nm/°C in the range of 28.1 °C~35 °C, which is 10.3 times higher than that of an unfilled balloon-like structure (0.111 nm/°C). The system has the advantages of low cost and easy fabrication, which can potentially be used in high-precision temperature monitoring processes.

7.
Oral Dis ; 2024 May 12.
Artículo en Inglés | MEDLINE | ID: mdl-38735833

RESUMEN

BACKGROUND: Diabetes is accompanied by a high prevalence of hyposalivation, causing severe damage to oral and systemic health. Mitochondrial dynamics play important roles in the pathogenesis of various diabetic complications; however, little is known about their roles in diabetic hyposalivation. MATERIALS AND METHODS: A diabetic mouse model and a high glucose (HG)-induced diabetic submandibular gland (SMG) cell model were employed. RESULTS: More mitochondria surrounded by autophagosomes and higher expression of mitophagy-related proteins were detected in the SMGs of diabetic mice and HG-treated SMG cells. In diabetic SMGs, dynamin-related protein 1 (DRP1) was upregulated, whereas mitofusin-2 was downregulated both in vivo and in vitro. Shortened mitochondria and impaired mitochondrial functions were observed in the HG group. A DRP1-specific inhibitor, mdivi-1, suppressed mitochondrial fission and mitophagy, as well as restored mitochondrial functions in the HG condition. Moreover, the interaction of F-actin and DRP1 was enhanced in the diabetic group. Inhibiting F-actin with cytochalasin D repaired the injured effects of HG on mitochondrial dynamics and functions. Conversely, the F-actin-polymerization-inducer jasplakinolide aggravated mitochondrial fission and dysfunction. CONCLUSIONS: F-actin contributes to HG-evoked mitochondrial fission by interacting with DRP1, which induces mitophagy and impairs mitochondrial function in SMG cells, ultimately damaging the SMG.

8.
ACS Appl Mater Interfaces ; 16(21): 27785-27793, 2024 May 29.
Artículo en Inglés | MEDLINE | ID: mdl-38757309

RESUMEN

Flexible nanocomposite dielectrics with inorganic nanofillers exhibit great potential for energy storage devices in advanced microelectronics applications. However, high loading of inorganic nanofillers in the matrix results in an inhomogeneous electric field distribution, thereby hindering the improvement of the energy storage density (Ue) of the dielectrics. Herein, we proposed a strategy that utilized (00l)-oriented barium titanate (BT) single-crystal platelets to fabricate trilayered nanocomposite dielectrics for energy storage applications. The trilayered nanocomposites consisted of two high-permittivity layers of (Ta2O5, Al2O3) codoped TiO2 nanoparticles (Ta-Al@TiO2 nps) dispersed in a poly(vinylidene fluoride) (PVDF) matrix to facilitate large electric displacement and a middle layer of (00l)-oriented BT single-crystal platelets to provide high breakdown strength. Hence, the trilayered PVDF/Ta-Al@TiO2 nps/BT single-crystal platelet nanocomposite film attains an outstanding Ue of 16.9 J cm-3 at 370 kV mm-1, which is ∼625% higher than that of the single-layer PVDF/Ta-Al@TiO2 nps film. Finite element simulation further clarified that the successive inner layer of highly (00l)-oriented BT single-crystal platelets could effectively restrain the propagation of electrical treeing in trilayered nanocomposites. This research offers an effective approach for developing flexible dielectric capacitors with an excellent energy storage performance.

9.
Sci Data ; 11(1): 508, 2024 May 16.
Artículo en Inglés | MEDLINE | ID: mdl-38755209

RESUMEN

Stripe rust fungus Puccinia striiformis f. sp. tritici (Pst) is a destructive pathogen of wheat worldwide. Pst has a macrocyclic-heteroecious lifecycle, in which one-celled urediniospores are dikaryotic, each nucleus containing one haploid genome. We successfully generated the first fully haplotype-resolved and nearly gap-free chromosome-scale genome assembly of Pst by combining PacBio HiFi sequencing and trio-binning strategy. The genome size of the two haploid assemblies was 75.59 Mb and 75.91 Mb with contig N50 of 4.17 Mb and 4.60 Mb, and both had 18 pseudochromosomes. The high consensus quality values of 55.57 and 59.02 for both haplotypes confirmed the correctness of the assembly. Of the total 18 chromosomes, 15 and 16 were gapless while there were only five and two gaps for the remaining chromosomes of the two haplotypes, respectively. In total, 15,046 and 15,050 protein-coding genes were predicted for the two haplotypes, and the complete BUSCO scores achieved 97.7% and 97.9%, respectively. The genome will lay the foundation for further research on genetic variations and the evolution of rust fungi.


Asunto(s)
Genoma Fúngico , Haplotipos , Puccinia , Triticum , Cromosomas Fúngicos/genética , Enfermedades de las Plantas/microbiología , Puccinia/genética , Triticum/microbiología
10.
Int Immunopharmacol ; 134: 112218, 2024 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-38733828

RESUMEN

OBJECTIVE: Long noncoding RNAs (lncRNAs) play an increasingly important role in various autoimmune diseases. We aimed to characterize the expression profiles of lncRNAs in peripheral blood mononuclear cells (PBMCs) from RA patients and to assess the potential of these lncRNAs as RA biomarkers. METHODS: Whole-transcriptome sequencing was used to establish a lncRNA expression profile. A total of 155 RA patients, 145 healthy controls, 59 systemic lupus erythematosus (SLE) patients and 59 primary Sjögren's syndrome (pSS) patients were recruited for this study. Four candidate lncRNAs (linc00152, lnc-ADM-1, ITSN1-2, and lnc-FTH1-7) were validated via qRT-PCR in independent samples, and their expression, association with RA clinical features and value as RA biomarkers were evaluated. RESULTS: Linc00152 and lnc-ADM-1 exhibited upregulated expression (p = 0.001, p = 0.014, respectively), while ITSN1-2 and lnc-FTH1-7 exhibited downregulated expression (both p < 0.001, respectively) in RA patients compared to controls. Lnc-ADM-1 and lnc-FTH1-7 expression correlated positively with the C4 level (p = 0.016 and p = 0.012, respectively). ITSN1-2 levels were negatively associated with CRP levels (p = 0.024). Linc00152, lnc-ADM-1, ITSN1-2, and lnc-FTH1-7 showed potential as RA biomarkers, with the four-lncRNA panel distinguishing RA patients from controls, SLE patients, or pSS patients (AUC = 0.886, 0.746, and 0.749, respectively). CONCLUSION: The altered expression of linc00152, lnc-ADM-1, ITSN1-2 and lnc-FTH1-7 in RA patients suggested that these genes may serve as potential biomarkers for RA and could be involved in its pathogenesis.


Asunto(s)
Artritis Reumatoide , Biomarcadores , Leucocitos Mononucleares , ARN Largo no Codificante , Humanos , ARN Largo no Codificante/genética , ARN Largo no Codificante/sangre , Artritis Reumatoide/genética , Artritis Reumatoide/sangre , Leucocitos Mononucleares/metabolismo , Masculino , Femenino , Biomarcadores/sangre , Persona de Mediana Edad , Adulto , Lupus Eritematoso Sistémico/genética , Lupus Eritematoso Sistémico/sangre , Lupus Eritematoso Sistémico/diagnóstico , Síndrome de Sjögren/genética , Síndrome de Sjögren/sangre , Perfilación de la Expresión Génica , Anciano
11.
Expert Rev Vaccines ; 23(1): 570-583, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38733272

RESUMEN

INTRODUCTION: The mRNA vaccine technologies have progressed rapidly in recent years. The COVID-19 pandemic has accelerated the application of mRNA vaccines, with research and development and clinical trials underway for many vaccines. Application of the quality by design (QbD) framework to mRNA vaccine development and establishing standardized quality control protocols for mRNA vaccines are essential for the continued development of high-quality mRNA vaccines. AREAS COVERED: mRNA vaccines include linear mRNA, self-amplifying mRNA, and circular RNA vaccines. This article summarizes the progress of research on quality control of these three types of vaccines and presents associated challenges and considerations. EXPERT OPINION: Although there has been rapid progress in research on linear mRNA vaccines, their degradation patterns remain unclear. In addition, standardized assays for key impurities, such as residual dsRNA and T7 RNA polymerase, are still lacking. For self-amplifying mRNA vaccines, a key focus should be control of stability in vivo and in vitro. For circular RNA vaccines, standardized assays, and reference standards for determining degree of circularization should be established and optimized.


Asunto(s)
Vacunas contra la COVID-19 , COVID-19 , Control de Calidad , Vacunas de ARNm , Humanos , Vacunas contra la COVID-19/inmunología , Vacunas contra la COVID-19/administración & dosificación , Vacunas contra la COVID-19/normas , COVID-19/prevención & control , Vacunas Sintéticas/inmunología , Vacunas Sintéticas/administración & dosificación , Desarrollo de Vacunas , Animales , ARN Mensajero/genética , ARN Mensajero/inmunología , SARS-CoV-2/inmunología , SARS-CoV-2/genética
12.
Int J Mol Med ; 53(5)2024 05.
Artículo en Inglés | MEDLINE | ID: mdl-38577932

RESUMEN

Pyroptosis, a programmed cell death marked by lytic and inflammatory characteristics, plays a crucial role in non­infectious inflammation­related diseases but can lead to detrimental outcomes when dysregulated. Stem cells have emerged as key players in modulating pyroptosis through paracrine signaling, offering a novel avenue for tissue repair and regeneration. The present review delved into previous studies elucidating the intricate interplay between stem cells and pyroptosis, emphasizing the potential of stem cell­based therapies in regulating pyroptotic pathways. The exploration of this dynamic interaction holds promise for developing strategies to harness stem cells for effective tissue repair and regeneration in the context of inflammation­related diseases.


Asunto(s)
Apoptosis , Piroptosis , Humanos , Células Madre , Inflamación
13.
Biomed Pharmacother ; 174: 116585, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38615611

RESUMEN

Emerging research into metabolic dysfunction-associated steatotic liver disease (MASLD) up until January 2024 has highlighted the critical role of cuproptosis, a unique cell death mechanism triggered by copper overload, in the disease's development. This connection offers new insights into MASLD's complex pathogenesis, pointing to copper accumulation as a key factor that disrupts lipid metabolism and insulin sensitivity. The identification of cuproptosis as a significant contributor to MASLD underscores the potential for targeting copper-mediated pathways for novel therapeutic approaches. This promising avenue suggests that managing copper levels could mitigate MASLD progression, offering a fresh perspective on treatment strategies. Further investigations into how cuproptosis influences MASLD are essential for unraveling the detailed mechanisms at play and for identifying effective interventions. The focus on copper's role in liver health opens up the possibility of developing targeted therapies that address the underlying causes of MASLD, moving beyond symptomatic treatment to tackle the root of the problem. The exploration of cuproptosis in the context of MASLD exemplifies the importance of understanding metal homeostasis in metabolic diseases and represents a significant step forward in the quest for more effective treatments. This research direction lights path for innovative MASLD management and reversal.


Asunto(s)
Apoptosis , Cobre , Hígado Graso , Animales , Humanos , Cobre/metabolismo , Hígado Graso/metabolismo , Resistencia a la Insulina , Metabolismo de los Lípidos , Hígado/metabolismo , Hígado/patología , Enfermedades Metabólicas/metabolismo
14.
J Virol ; 98(5): e0195923, 2024 May 14.
Artículo en Inglés | MEDLINE | ID: mdl-38634598

RESUMEN

The role of Culex mosquitoes in the transmission of Japanese encephalitis virus (JEV) is crucial, yet the mechanisms of JEV infection in these vectors remain unclear. Previous research has indicated that various host factors participate in JEV infection. Herein, we present evidence that mosquito sialic acids enhance JEV infection both in vivo and in vitro. By treating mosquitoes and C6/36 cells with neuraminidase or lectin, the function of sialic acids is effectively blocked, resulting in significant inhibition of JEV infection. Furthermore, knockdown of the sialic acid biosynthesis genes in Culex mosquitoes also leads to a reduction in JEV infection. Moreover, our research revealed that sialic acids play a role in the attachment of JEV to mosquito cells, but not in its internalization. To further explore the mechanisms underlying the promotion of JEV attachment by sialic acids, we conducted immunoprecipitation experiments to confirm the direct binding of sialic acids to the last α-helix in JEV envelope protein domain III. Overall, our study contributes to a molecular comprehension of the interaction between mosquitoes and JEV and offers potential strategies for preventing the dissemination of flavivirus in natural environments.IMPORTANCEIn this study, we aimed to investigate the impact of glycoconjugate sialic acids on mosquito infection with Japanese encephalitis virus (JEV). Our findings demonstrate that sialic acids play a crucial role in enhancing JEV infection by facilitating the attachment of the virus to the cell membrane. Furthermore, our investigation revealed that sialic acids directly bind to the final α-helix in the JEV envelope protein domain III, thereby accelerating virus adsorption. Collectively, our results highlight the significance of mosquito sialic acids in JEV infection within vectors, contributing to a better understanding of the interaction between mosquitoes and JEV.


Asunto(s)
Culex , Virus de la Encefalitis Japonesa (Especie) , Encefalitis Japonesa , Ácidos Siálicos , Acoplamiento Viral , Animales , Ratones , Línea Celular , Culex/virología , Culex/metabolismo , Virus de la Encefalitis Japonesa (Especie)/fisiología , Virus de la Encefalitis Japonesa (Especie)/metabolismo , Encefalitis Japonesa/virología , Encefalitis Japonesa/metabolismo , Mosquitos Vectores/virología , Neuraminidasa/metabolismo , Neuraminidasa/genética , Ácidos Siálicos/metabolismo , Proteínas del Envoltorio Viral/metabolismo , Proteínas del Envoltorio Viral/genética , Internalización del Virus
15.
Talanta ; 275: 126086, 2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-38663071

RESUMEN

Laser-induced breakdown spectroscopy (LIBS), as an elemental composition analysis technique, has many unique advantages and great potential for applications in water detection. However, the quality of LIBS spectral signals, such as signal-to-noise ratio and stability, is often poor due to the matrix effects of water, limiting its practical performance. To effectively remove the inherent weak radiation in experimental spectral data that can be easily mistaken for noise, this paper proposes a denoising algorithm for processing spectral data using a self-built blank sample spectral database of deionized water samples, and designs a complete data processing workflow. It includes steps such as blank sample data screening, internal standard correction, blank sample correction, and spectral smoothing. Against the backdrop of marine applications, experimental spectral data for target elements Na, Mg, Ca, K, Sr, and Li were processed with this algorithm. The results show that after algorithm processing, the spectral quality was significantly improved, with the signal-to-noise ratio and detection limits of various elements improved by at least one order of magnitude. The signal-for Li increased by up to 36 times, and the detection limit for K decreased by up to 25.2 times. Additionally, tiny spectral peaks that could not be observable in the original spectral data could be effectively extracted after processing. From a technical implementation perspective, the database establishment and data process are simple and practical, with universal applicability. Therefore, this method has good potential and wide foregrounds in many other water sample LIBS detection technologies.

16.
Cancer Lett ; 591: 216893, 2024 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-38636892

RESUMEN

The oncogenic properties of Nucleobindin2 (NUCB2) have been observed in various cancer types. Nevertheless, the precise understanding of the biological functions and regulatory mechanisms of NUCB2 in osteosarcoma remains limited. This investigation reported that NUCB2 was significantly increased upon glucose deprivation-induced metabolic stress. Elevated NUCB2 suppressed glucose deprivation-induced cell death and reactive oxygen species (ROS) increase. Depletion of NUCB2 resulted in a reduction in osteosarcoma cell proliferation as well as metastatic potential in vitro and in vivo. Mechanically, NUCB2 ablation suppressed C-X-C Motif Chemokine Ligand 8 (CXCL8) expression which then reduced programmed cell death 1 ligand 1 (PD-L1) expression and stimulated anti-tumor immunity mediated through cytotoxic T cells. Importantly, a combination of NUCB2 depletion with anti-PD-L1 treatment improved anti-tumor T-cell immunity in vivo. Moreover, we further demonstrated that NUCB2 interacted with NUCKS1 to inhibit its degradation, which is responsible for the transcriptional regulation of CXCL8 expression. Altogether, the outcome emphasizes the function of NUCB2 in osteosarcoma and indicates that NUCB2 elevates osteosarcoma progression and immunosuppressive microenvironment through the NUCKS1/CXCL8 pathway.


Asunto(s)
Neoplasias Óseas , Proteínas de Unión al Calcio , Progresión de la Enfermedad , Interleucina-8 , Osteosarcoma , Microambiente Tumoral , Osteosarcoma/inmunología , Osteosarcoma/patología , Osteosarcoma/metabolismo , Osteosarcoma/genética , Humanos , Animales , Línea Celular Tumoral , Interleucina-8/metabolismo , Interleucina-8/genética , Ratones , Neoplasias Óseas/inmunología , Neoplasias Óseas/patología , Neoplasias Óseas/metabolismo , Neoplasias Óseas/genética , Proteínas de Unión al Calcio/metabolismo , Proteínas de Unión al Calcio/genética , Microambiente Tumoral/inmunología , Proteínas de Unión al ADN/genética , Proteínas de Unión al ADN/metabolismo , Proliferación Celular , Proteínas del Tejido Nervioso/metabolismo , Proteínas del Tejido Nervioso/genética , Regulación Neoplásica de la Expresión Génica , Antígeno B7-H1/metabolismo , Antígeno B7-H1/genética , Linfocitos T Citotóxicos/inmunología , Transducción de Señal , Especies Reactivas de Oxígeno/metabolismo
17.
Front Cardiovasc Med ; 11: 1334457, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38606383

RESUMEN

Early-stage infective endocarditis (IE) can lead to severe complications, including infarctions and metastatic infections caused by inflammatory embolus shedding. Common embolism sites include the brain, spleen, kidneys, lungs, and intestines. Additionally, acute heart failure (AHF) can occur in up to 40% of cases, and its presence can impact the clinical outcomes of patients with IE. Cardiogenic shock (CGS) is often more likely to occur after AHF has taken place. If bacteria invade the blood, infectious shock can occur. Patients with IE can experience simple CGS, septic shock, or a combination of the two. Extracorporeal membrane oxygenation (ECMO) typically serves as a Bridge for Heart failure and Cardiogenic shock. Previous research indicates that there are limited reports of ECMO support for patients with IE after CGS has occurred. Because CGS may occur at any time during IE treatment, it is important to understand the timing of ECMO auxiliary support and how to carry out comprehensive treatment after support. Timely treatment can help to reduce or avoid the occurrence of serious complications and improve the prognosis of patients with IE. Our work combines a case study to review the ECMO support of IE patients after CGS through a literature review. Overall, we suggest that when patients with IE have large bacterial thrombosis and a greater risk of shedding, it is recommended to carefully evaluate the indications and contraindications for ECMO after discussion by a multidisciplinary team (MDT). Still, active surgical treatment at an early stage is recommended.

18.
Front Immunol ; 15: 1383936, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38638432

RESUMEN

In the quest to address the critical shortage of donor organs for transplantation, xenotransplantation stands out as a promising solution, offering a more abundant supply of donor organs. Yet, its widespread clinical adoption remains hindered by significant challenges, chief among them being immunological rejection. Central to this issue is the role of the complement system, an essential component of innate immunity that frequently triggers acute and chronic rejection through hyperacute immune responses. Such responses can rapidly lead to transplant embolism, compromising the function of the transplanted organ and ultimately causing graft failure. This review delves into three key areas of xenotransplantation research. It begins by examining the mechanisms through which xenotransplantation activates both the classical and alternative complement pathways. It then assesses the current landscape of xenotransplantation from donor pigs, with a particular emphasis on the innovative strides made in genetically engineering pigs to evade complement system activation. These modifications are critical in mitigating the discordance between pig endogenous retroviruses and human immune molecules. Additionally, the review discusses pharmacological interventions designed to support transplantation. By exploring the intricate relationship between the complement system and xenotransplantation, this retrospective analysis not only underscores the scientific and clinical importance of this field but also sheds light on the potential pathways to overcoming one of the major barriers to the success of xenografts. As such, the insights offered here hold significant promise for advancing xenotransplantation from a research concept to a viable clinical reality.


Asunto(s)
Activación de Complemento , Rechazo de Injerto , Animales , Humanos , Porcinos , Trasplante Heterólogo , Animales Modificados Genéticamente , Estudios Retrospectivos , Rechazo de Injerto/prevención & control , Proteínas del Sistema Complemento
19.
FEBS Lett ; 598(12): 1513-1531, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38664231

RESUMEN

Mitochondria harbor the oxidative phosphorylation (OXPHOS) system to sustain cellular respiration. However, the transcriptional regulation of OXPHOS remains largely unexplored. Through the cancer genome atlas (TCGA) transcriptome analysis, transcription factor THAP domain-containing 3 (THAP3) was found to be strongly associated with OXPHOS gene expression. Mechanistically, THAP3 recruited the histone methyltransferase SET and MYND domain-containing protein 3 (SMYD3) to upregulate H3K4me3 and promote OXPHOS gene expression. The levels of THAP3 and SMYD3 were altered by metabolic cues. They collaboratively supported liver cancer cell proliferation and colony formation. In clinical human liver cancer, both of them were overexpressed. THAP3 positively correlated with OXPHOS gene expression. Together, THAP3 cooperates with SMYD3 to epigenetically upregulate cellular respiration and liver cancer cell proliferation.


Asunto(s)
Carcinoma Hepatocelular , Proliferación Celular , Epigénesis Genética , Regulación Neoplásica de la Expresión Génica , N-Metiltransferasa de Histona-Lisina , Neoplasias Hepáticas , Fosforilación Oxidativa , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patología , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patología , N-Metiltransferasa de Histona-Lisina/genética , N-Metiltransferasa de Histona-Lisina/metabolismo , Proliferación Celular/genética , Mitocondrias/metabolismo , Mitocondrias/genética , Respiración de la Célula/genética , Línea Celular Tumoral , Histonas/metabolismo , Histonas/genética , Proteínas de Unión al ADN/genética , Proteínas de Unión al ADN/metabolismo
20.
EMBO J ; 43(12): 2337-2367, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38649537

RESUMEN

Mitochondria are cellular powerhouses that generate energy through the electron transport chain (ETC). The mitochondrial genome (mtDNA) encodes essential ETC proteins in a compartmentalized manner, however, the mechanism underlying metabolic regulation of mtDNA function remains unknown. Here, we report that expression of tricarboxylic acid cycle enzyme succinate-CoA ligase SUCLG1 strongly correlates with ETC genes across various TCGA cancer transcriptomes. Mechanistically, SUCLG1 restricts succinyl-CoA levels to suppress the succinylation of mitochondrial RNA polymerase (POLRMT). Lysine 622 succinylation disrupts the interaction of POLRMT with mtDNA and mitochondrial transcription factors. SUCLG1-mediated POLRMT hyposuccinylation maintains mtDNA transcription, mitochondrial biogenesis, and leukemia cell proliferation. Specifically, leukemia-promoting FMS-like tyrosine kinase 3 (FLT3) mutations modulate nuclear transcription and upregulate SUCLG1 expression to reduce succinyl-CoA and POLRMT succinylation, resulting in enhanced mitobiogenesis. In line, genetic depletion of POLRMT or SUCLG1 significantly delays disease progression in mouse and humanized leukemia models. Importantly, succinyl-CoA level and POLRMT succinylation are downregulated in FLT3-mutated clinical leukemia samples, linking enhanced mitobiogenesis to cancer progression. Together, SUCLG1 connects succinyl-CoA with POLRMT succinylation to modulate mitochondrial function and cancer development.


Asunto(s)
Biogénesis de Organelos , Succinato-CoA Ligasas , Animales , Humanos , Ratones , Acilcoenzima A/metabolismo , Acilcoenzima A/genética , Línea Celular Tumoral , Proliferación Celular , Progresión de la Enfermedad , ADN Mitocondrial/metabolismo , ADN Mitocondrial/genética , ARN Polimerasas Dirigidas por ADN/metabolismo , ARN Polimerasas Dirigidas por ADN/genética , Leucemia/metabolismo , Leucemia/genética , Leucemia/patología , Mitocondrias/metabolismo , Mitocondrias/genética , Proteínas Mitocondriales/metabolismo , Proteínas Mitocondriales/genética , Succinato-CoA Ligasas/metabolismo , Succinato-CoA Ligasas/genética
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