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1.
Int J Ophthalmol ; 17(9): 1675-1680, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39296571

RESUMEN

AIM: To evaluate the clinical effect of a new surgery technique (covering corneal stromal lenticule, CSL) for macular hole (MH) in pathological myopia. METHODS: This was a prospective non-randomized series case study. Fourteen eyes of 14 patients whose axial length were more than 29 mm and suffered from MH and macular hole retinal detachment (MHRD) were included in this study. All cases were treated with 25-gauge pars plana vitrectomy (PPV) with internal limiting membrane (ILM) peeling, covering CSL and C3F8 gas tamponade. These cases were followed for 6mo, and the best-corrected visual acuity (BCVA), healing status of MH, the reattached rate of retinal detachment (RD), and reoperation rate were analyzed. RESULTS: All cases were successfully performed the surgery and the postoperative follow-up was completed. After surgery, MHs were healed in all 14 eyes (100%, 14/14) after assessed by optical coherence tomography. The reattachment of retina was achieved in all 6 eyes (100%, 6/6) with MHRD. BCVA was improved in 12 eyes (85.71%, 12/14), and had no significant change in 2 eyes (14.29%, 2/14). The overall mean BCVA was improved from 1.80±0.77 to 0.82±0.46 logMAR (F=10.46, P<0.01). No serious complications occurred in all cases. CONCLUSION: The new surgery technique (covering CSL) has high reattached rate of RD and high healing rate of MH in pathological myopia in the preliminary study. And it can effectively improve the visual function of patients. This new technique offers meaningful new ideas for treating refractory MH in pathological myopia.

2.
J Hazard Mater ; 480: 135856, 2024 Sep 16.
Artículo en Inglés | MEDLINE | ID: mdl-39298956

RESUMEN

Volatile organic compounds (VOCs) have proven to be hazardous to the human respiratory system. However, the underlying biological mechanisms remain poorly understood. Therefore, targeted determination of eleven VOC metabolites (mVOCs) along with the nontargeted metabolomic analysis was performed on urine samples collected from lung cancer patients and healthy individuals. Nine mVOCs mainly derived from aldehydes, alkenes, amides, and aromatics were detected in > 90 % of the urine samples, suggesting that the participants were ubiquitously exposed to these typical VOCs. A molecular gatekeeper discovery workflow was employed to link the exposure biomarkers with correlated clusters of endogenous metabolites. As a result, multiple metabolic pathways, including amino acid metabolism, steroid hormone biosynthesis and metabolism, and fatty acid ß-oxidation were connected with VOC exposure. Furthermore, 16 of 73 molecular gatekeepers were associated with lung cancer and pointed to a few disrupted metabolic pathways related to hydroxysteroids and acylcarnitine. The shift in molecular profiles was validated in rat model post VOC administration. Thereinto, the up-regulation of enzymes involved in acylcarnitine synthesis and transport in rat lung tissues highlighted that the mitochondrial dysfunction may be a potential carcinogenic mechanism. Our findings provide new insights into the mechanisms underlying lung cancer induced by VOC exposure.

3.
Ecol Evol ; 14(8): e70055, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39157670

RESUMEN

Soil fungi participate in various ecosystem processes and are important factors driving the restoration of degraded forests. However, little is known about the changes in fungal diversity and potential functions under the development of different vegetation types during natural (secondary forest succession) and anthropogenic (reforestation) forest restoration. In this study, we selected typical forest succession sequences (including Pinus densiflora Siebold & Zucc., pine-broadleaf mixed forest of P. densiflora and Quercus acutissima Carruth., and Q. acutissima), as well as natural secondary deciduous broadleaved mixed forests and planted forests of Robinia pseudoacacia on Kunyu Mountain for analysis. We used ITS rRNA gene sequencing to characterize fungal communities and used the FUNGuild database to predict fungal functional groups. The results showed that forest succession affected fungal ß-diversity, but not the α-diversity. There was a significant increase in Basidiomycota and a decrease in Ascomycota in the later successional stage, accompanied by an increase in the functional groups of ectomycorrhizal fungi (ECM). Conversely, planted forests exhibited decreased fungal α-diversity and altered community compositions, characterized by fewer Basidiomycota and more Ascomycota and Mucoromycota. Planted forests led to a decrease in the relative abundances of ECM and an increase in animal pathogens. The TK content was the major factor explaining the distinction in fungal communities among the three successional stages, whereas pH, AP, and NH4 + were the major factors explaining community variations between natural and planted forests. Changes in vegetation types significantly affected the diversity and functional groups of soil fungal communities during forest succession and reforestation, providing key insights for forest ecosystem management in temperate forests.

4.
Gels ; 10(8)2024 Aug 12.
Artículo en Inglés | MEDLINE | ID: mdl-39195057

RESUMEN

This study aimed to develop a product that closely replicates the texture and appearance of tripe. The effect of three different proteins (soy protein isolate (SPI), pea protein isolate (PPI), and whey protein isolate (WPI)) at different protein levels and processing conditions (heating (90 °C, 1 h) followed by cooling (4 °C, 12 h) and heating (90 °C, 1h) followed by freezing (-18 °C, 12 h)) of konjac glucomannan (KGM) was analyzed. The optimal formulations for simulating tripe were screened by examining their similarity to real tripe in terms of texture, color, and sensory experience. The screened formulations were also subjected to a preliminary mechanistic investigation. The results show that all three proteins improved the gel's textural properties to varying degrees. At the same concentration, the hardness and chewiness of the KGM/WPI composite gel were significantly higher than those of the other two KGM/protein composite gels, among which the composite gel obtained by adding 8% WPI and 5% KGM heating-frozen (FWK4) had the greatest hardness and chewiness of 4338.07 g and 2313.76, respectively, and the springiness differences in all of the composite gels were small. In addition, the addition of protein increased the whiteness of the hybrid gels, with WPI having the most significant effect on the whiteness of the composite gels (whiteness increased from 30.25 to 62.80 as the concentration of WPI increased from 0 to 10%). Freezing increased composite gel hardness and chewiness, but reduced gel springiness and whiteness. Cluster analysis showed that the composite gel obtained by heating-cooling 8% WPI and 5% KGM (WK4) was very similar to the real tripe in terms of chewiness and whiteness, and WK4 had the highest sensory scores for color, tissue morphology, tactile sensation, taste, and odor. The acceptability score in terms of tissue morphology reached 4.3. Meanwhile, the characterization results of WK4 indicate the presence of large junction areas in the gel network. Fourier transform infrared spectroscopy (FTIR) analysis, X-ray diffraction, and intermolecular force contributions indicated that the incorporation of WPI promoted integral interactions, and that hydrophobic interactions and disulfide bonding played a key role in the WK4 composite gel system. Moreover, scanning electron microscopy (SEM) also showed that the combination of WPI and konjac glucan resulted in a more compact gel structure. This study is informative for the development of the field of bionic tripe processing.

5.
Cell Host Microbe ; 32(7): 1045-1047, 2024 Jul 10.
Artículo en Inglés | MEDLINE | ID: mdl-38991501

RESUMEN

The microbiota can impact antitumor immunity, but whether the microbiota regulates omental antitumor immunity remains elusive. In this issue of Cell Host & Microbe, Meza-Perez et al. demonstrated that Proteobacteria consume arginine to increase Treg cell suppressive capacity and inhibit antitumor immune responses, promoting tumor growth in the omentum.


Asunto(s)
Arginina , Epiplón , Proteobacteria , Arginina/metabolismo , Animales , Epiplón/inmunología , Epiplón/microbiología , Humanos , Ratones , Microbioma Gastrointestinal/inmunología , Linfocitos T Reguladores/inmunología , Neoplasias/inmunología , Neoplasias/microbiología
6.
Sci Total Environ ; 946: 174435, 2024 Oct 10.
Artículo en Inglés | MEDLINE | ID: mdl-38964402

RESUMEN

The retreat of Himalayan glaciers and the expansion of glacial lakes due to global warming have increased the occurrence of glacial lake outburst debris flow (GLODF), posing a serious threat to downstream communities. However, there are gaps in understanding the changes in GLODF occurrence driven by climate change, which challenges disaster management and cross-border cooperation in the Himalayas. To consider this issue, our study presents a novel framework integrating environmental evolution, a process-driven indicator system, and a hybrid machine learning model to predict Himalayan GLODF occurrence in the 21st century. Our findings indicate ongoing temperature (0.27-0.60 °C/10a) and precipitation (1.30-5.00 %/10a) increases under both SSP245 and SSP585 scenarios. Meanwhile, Himalayan glaciers are projected to lose between 70 % and 86 % of their mass by 2100 compared to 2020. Additionally, 2722 ± 207 new glacial lakes are expected to emerge by 2100. GLODF occurrence probability index is anticipated to rise to 1.27-1.30 times the current levels, with the Western Himalayas and Indus basin as high-incidence areas. Currently and in the future, the China-Nepal border remains a hotspot for cross-border GLODF. Our framework offers valuable long-term insights into Himalayan GLODF occurrence trends in response to climate change.

7.
Small ; : e2402344, 2024 Jun 03.
Artículo en Inglés | MEDLINE | ID: mdl-38829023

RESUMEN

Lithium-sulfur batteries (LSBs) are still limited by some issues such as polysulfides shuttle and lithium dendrites. Recently, the concept "high-entropy" has been considered as the research hotspot and international frontier. Herein, a high entropy MXene (TiVCrMoC3Tx, HE-MXene) doped graphene is designed as the modified coating on commercial separators for LSBs. The HE-MXene affords multiple metal active sites, fast Li+ diffusion rate, and efficient adsorption toward polysulfide intermediates. Furthermore, strong lithophilic property is favorable for uniform Li+ deposition. The combination of in situ characterizations confirms TiVCrMoC3Tx effectively promotes the Li2S nucleation/dissolution kinetics, reduces the Li+ diffusion barrier, and exhibits favorable lithium uniform deposition behavior. This TiVCrMoC3Tx/G@PP provides a high-capacity retention rate after 1000 cycles at 1 C and 2 C, with a capacity decay rate of merely 0.021% and 0.022% per cycle. Surprisingly, the cell operates at a low potential of 48 mV while maintaining at 5 mA cm-2/5 mAh cm-2 for 4000 h. Furthermore, it still maintains a high-capacity retention rate under a high sulfur loading of 4.8/6.4 mg cm-2 and a low E/S ratio of 8.6/7.5 µg mL-1. This work reveals a technical roadmap for simultaneously addressing the cathode and anode challenge, thus achieving potential commercially viable LSBs.

9.
Sensors (Basel) ; 24(11)2024 Jun 05.
Artículo en Inglés | MEDLINE | ID: mdl-38894455

RESUMEN

The aim of infrared and visible image fusion is to generate a fused image that not only contains salient targets and rich texture details, but also facilitates high-level vision tasks. However, due to the hardware limitations of digital cameras and other devices, there are more low-resolution images in the existing datasets, and low-resolution images are often accompanied by the problem of losing details and structural information. At the same time, existing fusion algorithms focus too much on the visual quality of the fused images, while ignoring the requirements of high-level vision tasks. To address the above challenges, in this paper, we skillfully unite the super-resolution network, fusion network and segmentation network, and propose a super-resolution-based semantic-aware fusion network. First, we design a super-resolution network based on a multi-branch hybrid attention module (MHAM), which aims to enhance the quality and details of the source image, enabling the fusion network to integrate the features of the source image more accurately. Then, a comprehensive information extraction module (STDC) is designed in the fusion network to enhance the network's ability to extract finer-grained complementary information from the source image. Finally, the fusion network and segmentation network are jointly trained to utilize semantic loss to guide the semantic information back to the fusion network, which effectively improves the performance of the fused images on high-level vision tasks. Extensive experiments show that our method is more effective than other state-of-the-art image fusion methods. In particular, our fused images not only have excellent visual perception effects, but also help to improve the performance of high-level vision tasks.

10.
BMC Infect Dis ; 24(1): 643, 2024 Jun 26.
Artículo en Inglés | MEDLINE | ID: mdl-38926679

RESUMEN

BACKGROUND: Malassezia restricta, a lipophilic and lipodependent yeast belonging to the basidiomycetes group, is an opportunistic fungal pathogen associated with various skin diseases, including seborrheic dermatitis and dandruff. Typically, Malassezia infection in neonates manifests as fungemia or hematogenous dissemination to the bone or lungs. However, vertebral osteomyelitis caused by these fungi is rarely reported owing to non-specific clinical presentations and laboratory/imaging findings. The Pathogen Metagenomics Sequencing (PMseq) technique enables direct high-throughput sequencing of infected specimens, facilitating the rapid and accurate detection of all microorganisms in clinical samples through comprehensive reports. CASE PRESENTATION: A 52-year-old male was admitted to our hospital on July 20, 2022 with a 3-month history of ambulatory difficulties and localized low back pain. Magnetic Resonance Imaging (MRI) examination of the spinal column revealed irregular bone destruction affecting the L2, L3, and L5 vertebral bodies. Additionally, low T1 and high T2 intensity lesions were observed at the intervertebral discs between L3 and L5. The presumptive diagnosis of tuberculous spondylitis was made based on the imaging findings, despite negative results in all mycobacterium tests. However, the patient exhibited no improvement after receiving regular anti-tuberculosis treatment for 3 months. Subsequent MRI revealed an expansive abnormal signal within the vertebral body, leading to progressive bone destruction. The absence of spinal tuberculosis or other infective microorganisms was confirmed through culture from blood and pathological tissue from the L4 vertebral body. Subsequently, PMseq was performed on the specimens, revealing M. restricta as the predominant pathogen with the highest relative abundance value. The pathological examination revealed the presence of fungal mycelium in the L4 vertebral body, with positive findings on periodic Schiff-methenamine and periodic acid-Schiff staining. The anti-tuberculosis treatment was discontinued, and an antifungal combination of fluconazole and voriconazole was administered. All symptoms were resolved after 7 consecutive months of treatment, and the patient was able to ambulate autonomously. Vertebral lesions were reduced on MRI during the 13-month follow-up. CONCLUSIONS: M. restricta is not a commonly recognized pathogen associated with infectious vertebral osteomyelitis. However, PMseq can aid in diagnosis, timely treatment, and decision making for some non-specific infectious diseases.


Asunto(s)
Malassezia , Metagenómica , Osteomielitis , Humanos , Masculino , Osteomielitis/microbiología , Osteomielitis/diagnóstico , Osteomielitis/tratamiento farmacológico , Persona de Mediana Edad , Malassezia/genética , Malassezia/aislamiento & purificación , Imagen por Resonancia Magnética , Antifúngicos/uso terapéutico , Secuenciación de Nucleótidos de Alto Rendimiento
12.
Sensors (Basel) ; 24(10)2024 May 19.
Artículo en Inglés | MEDLINE | ID: mdl-38794086

RESUMEN

In recent years, hydrogel-based wearable flexible electronic devices have attracted much attention. However, hydrogel-based sensors are affected by structural fatigue, material aging, and water absorption and swelling, making stability and accuracy a major challenge. In this study, we present a DN-SPEZ dual-network hydrogel prepared using polyvinyl alcohol (PVA), sodium alginate (SA), ethylene glycol (EG), and ZnSO4 and propose a self-calibration compensation strategy. The strategy utilizes a metal salt solution to adjust the carrier concentration of the hydrogel to mitigate the resistance drift phenomenon to improve the stability and accuracy of hydrogel sensors in amphibious scenarios, such as land and water. The ExpGrow model was used to characterize the trend of the ∆R/R0 dynamic response curves of the hydrogels in the stress tests, and the average deviation of the fitted curves ϵ¯ was calculated to quantify the stability differences of different groups. The results showed that the stability of the uncompensated group was much lower than that of the compensated group utilizing LiCl, NaCl, KCl, MgCl2, and AlCl3 solutions (ϵ¯ in the uncompensated group in air was 276.158, 1.888, 2.971, 30.586, and 13.561 times higher than that of the compensated group in LiCl, NaCl, KCl, MgCl2, and AlCl3, respectively; ϵ¯ in the uncompensated group in seawater was 10.287 times, 1.008 times, 1.161 times, 4.986 times, 1.281 times, respectively, higher than that of the compensated group in LiCl, NaCl, KCl, MgCl2 and AlCl3). In addition, for the ranking of the compensation effect of different compensation solutions, the concentration of the compensation solution and the ionic radius and charge of the cation were found to be important factors in determining the compensation effect. Detection of events in amphibious environments such as swallowing, robotic arm grasping, Morse code, and finger-wrist bending was also performed in this study. This work provides a viable method for stability and accuracy enhancement of dual-network hydrogel sensors with strain and pressure sensing capabilities and offers solutions for sensor applications in both airborne and underwater amphibious environments.

13.
Cell Discov ; 10(1): 53, 2024 May 20.
Artículo en Inglés | MEDLINE | ID: mdl-38763950

RESUMEN

Peripheral CD8+ T cell number is tightly controlled but the precise molecular mechanism regulating this process is still not fully understood. In this study, we found that epilepsy patients with loss of function mutation of DEPDC5 had reduced peripheral CD8+ T cells, and DEPDC5 expression positively correlated with tumor-infiltrating CD8+ T cells as well as overall cancer patient survival, indicating that DEPDC5 may control peripheral CD8+ T cell homeostasis. Significantly, mice with T cell-specific Depdc5 deletion also had reduced peripheral CD8+ T cells and impaired anti-tumor immunity. Mechanistically, Depdc5-deficient CD8+ T cells produced high levels of xanthine oxidase and lipid ROS due to hyper-mTORC1-induced expression of ATF4, leading to spontaneous ferroptosis. Together, our study links DEPDC5-mediated mTORC1 signaling with CD8+ T cell protection from ferroptosis, thereby revealing a novel strategy for enhancing anti-tumor immunity via suppression of ferroptosis.

14.
World J Gastrointest Oncol ; 16(4): 1547-1563, 2024 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-38660652

RESUMEN

BACKGROUND: Increasing data indicated that long noncoding RNAs (lncRNAs) were directly or indirectly involved in the occurrence and development of tumors, including hepatocellular carcinoma (HCC). Recent studies had found that the expression of lncRNA HAND2-AS1 was downregulated in HCC tissues, but its role in HCC progression is unclear. Ultrasound targeted microbubble destruction mediated gene transfection is a new method to overexpress genes. AIM: To study the role of ultrasound microbubbles (UTMBs) mediated HAND2-AS1 in the progression of HCC, in order to provide a new reference for the treatment of HCC. METHODS: In vitro, we transfected HAND2-AS1 siRNA into HepG2 cells by UTMBs, and detected cell proliferation, apoptosis, invasion and epithelial-mesenchymal transition (EMT) by cell counting kit-8 assay, flow cytometry, Transwell invasion assay and Western blotting, respectively. In addition, we transfected miR-837-5p mimic into UTMBs treated cells and observed the changes of cell behavior. Next, the UTMBs treated HepG2 cells were transfected together with miR-837-5p mimic and tissue inhibitor of matrix metalloproteinase-2 (TIMP2) overexpression vector, and we detected cell proliferation, apoptosis, invasion and EMT. In vivo, we established a mouse model of subcutaneous transplantation of HepG2 cells and observed the effect of HAND2-AS1 silencing on tumor formation ability. RESULTS: We found that UTMBs carrying HAND2-AS1 restricted cell proliferation, invasion, and EMT, encouraged apoptosis, and HAND2-AS1 silencing eliminated the effect of UTMBs. Additionally, miR-873-5p targets the gene HAND2-AS1, which also targets the 3'UTR of TIMP2. And miR-873-5p mimic counteracted the impact of HAND2-AS1. Further, miR-873-5p mimic solely or in combination with pcDNA-TIMP2 had been transformed into HepG2 cells exposed to UTMBs. We discovered that TIMP2 reversed the effect of miR-873-5p mimic caused by the blocked signalling cascade for matrix metalloproteinase (MMP) 2/MMP9. In vivo results showed that HAND2-AS1 silencing significantly inhibited tumor formation in mice. CONCLUSION: LncRNA HAND2-AS1 promotes TIMP2 expression by targeting miR-873-5p to inhibit HepG2 cell growth and delay HCC progression.

15.
Cancer Discov ; 14(4): 653-657, 2024 Apr 04.
Artículo en Inglés | MEDLINE | ID: mdl-38571418

RESUMEN

SUMMARY: Nutrients are essential for supporting tumor growth and immune cell function in the tumor microenvironment, but emerging evidence reveals a paradoxical competition and collaboration between the metabolic demands of proliferating cancer cells and immune cell activation. Dietary interventions and metabolic immunoengineering offer promise to selectively modulate cancer and immune cell metabolism by targeting metabolic sensing processes rather than pathways directly, moving beyond conventional ideas and heralding an exciting new era of immunometabolism discovery and translation.


Asunto(s)
Neoplasias , Humanos , Neoplasias/metabolismo , Microambiente Tumoral
16.
Biochem Pharmacol ; 223: 116101, 2024 05.
Artículo en Inglés | MEDLINE | ID: mdl-38442793

RESUMEN

Colorectal cancer (CRC) is one of the most common causes of tumor-related deaths globally. Despite recent improvements in the comprehensive therapy of malignancy, metastatic CRC continues to have a poor prognosis. Human epidermal growth factor receptor 2 (HER2) is an established oncogenic driver, which is successfully targeted for breast and gastric cancers. Approximately 5% of CRC patients carry somatic HER2 mutations or gene amplification. In 2019, the U.S. Food and Drug Administration have approved trastuzumab and pertuzumab in combination with chemotherapy for the treatment of HER2-positive metastatic CRC. This approval marked a significant milestone in the treatment of CRC, as HER2-positive patients now have access to targeted therapies that can improve their outcomes. Yet, assessment for HER2 overexpression/ amplification in CRC has not been standardized. The resistance mechanisms to anti-HER2 therapy have been not clearly investigated in CRC. Although many unknowns remain, an improved understanding of these anti-HER2 agents will be essential for advanced CRC. In this review, we provide an overview of the role of HER2 in CRC as an oncogenic driver, a prognostic and predictive biomarker, and a clinically actionable target, as well as the current progress and challenges in the field.


Asunto(s)
Neoplasias Colorrectales , Receptor ErbB-2 , Humanos , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Pronóstico , Receptor ErbB-2/genética , Receptor ErbB-2/metabolismo , Trastuzumab
17.
Ann Plast Surg ; 92(3): 274-278, 2024 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-38394267

RESUMEN

BACKGROUND: In the setting of immediate breast reconstruction by deep inferior epigastric artery perforator (DIEP) flap, the excessive DIEP flap skin is de-epithelialized and then buried under the mastectomy skin. In this study, by virtue of tube flap technique, we hypothesize that the skin supposed to be abandoned could be transferred to the apex of reconstructed breast mound for nipple reconstruction. METHODS: A total of 60 female patients were recruited between January 2019 and December 2020. All these patients underwent mastectomy including nipple-areola complex and immediate DIEP flap breast reconstruction. A ladder-shaped pedicled flap was raised from the DIEP flap and rolled into a tube. The free end of tube flap was inset into the future nipple position of the reconstructed breast mound 1 week later. After revascularization for 1 month, we divided the previous pedicle and used the tube on the apex of the breast mound to recreate a new nipple. RESULTS: All reconstructed breasts and nipples survived well postoperatively. The average nipple projection was 12.5 ± 2.0 mm immediately after the surgery, which gradually decreased to 9.4 ± 1.5 mm at 1-year follow-up, with the projection loss from the initial measurement as 24.9% ± 1.8%. In total, 51 patients considered the overall impression of breast and nipple reconstruction to be very good or good. CONCLUSIONS: We provided an ideal technique that could improve the maintenance of reconstructed nipple projection and have aesthetically acceptable outcomes, without DIEP flap tissue loss, breast mound distortion, or additional scars.


Asunto(s)
Neoplasias de la Mama , Mamoplastia , Colgajo Perforante , Femenino , Humanos , Mastectomía/métodos , Pezones/cirugía , Colgajo Perforante/irrigación sanguínea , Arterias Epigástricas/cirugía , Neoplasias de la Mama/cirugía , Satisfacción del Paciente , Estudios Retrospectivos , Mamoplastia/métodos
18.
Immunity ; 57(3): 528-540.e6, 2024 Mar 12.
Artículo en Inglés | MEDLINE | ID: mdl-38417442

RESUMEN

RNA splicing is involved in cancer initiation and progression, but how it influences host antitumor immunity in the metabolically abnormal tumor microenvironment (TME) remains unclear. Here, we demonstrate that lactate modulates Foxp3-dependent RNA splicing to maintain the phenotypic and functional status of tumor-infiltrating regulatory T (Treg) cells via CTLA-4. RNA splicing in Treg cells was correlated with the Treg cell signatures in the TME. Ubiquitin-specific peptidase 39 (USP39), a component of the RNA splicing machinery, maintained RNA-splicing-mediated CTLA-4 expression to control Treg cell function. Mechanistically, lactate promoted USP39-mediated RNA splicing to facilitate CTLA-4 expression in a Foxp3-dependent manner. Moreover, the efficiency of CTLA-4 RNA splicing was increased in tumor-infiltrating Treg cells from patients with colorectal cancer. These findings highlight the immunological relevance of RNA splicing in Treg cells and provide important insights into the environmental mechanism governing CTLA-4 expression in Treg cells.


Asunto(s)
Neoplasias , Linfocitos T Reguladores , Humanos , Antígeno CTLA-4 , Factores de Transcripción Forkhead/genética , Ácido Láctico/metabolismo , Linfocitos Infiltrantes de Tumor , Neoplasias/genética , Neoplasias/metabolismo , Microambiente Tumoral , Proteasas Ubiquitina-Específicas/metabolismo
19.
Nat Commun ; 15(1): 122, 2024 01 02.
Artículo en Inglés | MEDLINE | ID: mdl-38167862

RESUMEN

Targeting tumor-infiltrating regulatory T cells (Tregs) is an efficient way to evoke an anti-tumor immune response. However, how Tregs maintain their fragility and stability remains largely unknown. IFITM3 and STAT1 are interferon-induced genes that play a positive role in the progression of tumors. Here, we showed that IFITM3-deficient Tregs blunted tumor growth by strengthening the tumor-killing response and displayed the Th1-like Treg phenotype with higher secretion of IFNγ. Mechanistically, depletion of IFITM3 enhances the translation and phosphorylation of STAT1. On the contrary, the decreased IFITM3 expression in STAT1-deficient Tregs indicates that STAT1 conversely regulates the expression of IFITM3 to form a feedback loop. Blocking the inflammatory cytokine IFNγ or directly depleting STAT1-IFITM3 axis phenocopies the restored suppressive function of tumor-infiltrating Tregs in the tumor model. Overall, our study demonstrates that the perturbation of tumor-infiltrating Tregs through the IFNγ-IFITM3-STAT1 feedback loop is essential for anti-tumor immunity and constitutes a targetable vulnerability of cancer immunotherapy.


Asunto(s)
Neoplasias , Linfocitos T Reguladores , Humanos , Retroalimentación , Neoplasias/genética , Neoplasias/terapia , Citocinas/metabolismo , Factores de Transcripción Forkhead/metabolismo , Proteínas de la Membrana/metabolismo , Proteínas de Unión al ARN/metabolismo , Factor de Transcripción STAT1/genética , Factor de Transcripción STAT1/metabolismo
20.
Open Med (Wars) ; 19(1): 20230845, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38205151

RESUMEN

Serine/threonine kinase 11 (STK11), a tumor suppressor gene, exhibits frequent mutations in lung adenocarcinoma (LUAD). However, the specific molecular mechanisms by which STK11 mutations exert an influence on the biosynthesis of monounsaturated fatty acids (MUFAs) and subsequently affect ferroptosis in LUAD remain indistinct. In this study, bioinformatic analysis was employed to probe into the linkage between STK11 and key inhibitory genes of ferroptosis, namely SLC7A11 and SCD1, in LUAD tissues. Quantitative reverse transcription polymerase chain reaction was employed to assess the expression of STK11 in both wild-type and mutant STK11 LUAD cells, cell counting kit-8 to assess cell viability, and flow cytometry to detect apoptosis. A transmission electron microscope was utilized to observe mitochondrial morphology, and Western blot to ascertain the protein expression of STK11, ferroptosis-related proteins, and the enzyme SCD1 involved in MUFA synthesis. Oil red O staining was employed to test the distribution of lipid droplets in cancer cells, and a lipid quantification method to measure the content of MUFAs. Commercial kits were employed to assess the levels of lipid reactive oxygen species, malondialdehyde, glutathione, and Fe2+ in cells. The result revealed a negative correlation between STK11 and SLC7A11 as well as SCD1, with STK11 expression downregulated in mutant STK11 LUAD cells. Furthermore, STK11 mutations were found to suppress ferroptosis in LUAD cells by affecting MUFA synthesis. Subsequent rescue assays demonstrated that STK11 mutations hindered ferroptosis by impacting the synthesis of MUFAs in LUAD cells. This study provided evidence that STK11 mutations suppressed ferroptosis in LUAD cells by promoting MUFA synthesis, thus offering a novel research direction in the management of LUAD.

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