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1.
Nat Cell Biol ; 2024 Jul 22.
Artículo en Inglés | MEDLINE | ID: mdl-39039181

RESUMEN

Immunotherapy elicits a systemic antitumour immune response in peripheral circulating T cells. However, the T cell trafficking circuit between organs and their contributions to antitumour immunity remain largely unknown. Here we show in multiple mouse leukaemia models that high infiltration of leukaemic cells in bone marrow (BM) stimulates the transition of CD8+CD44+CD62L+ central memory T cells into CD8+CD44-CD62L- T cells, designated as inter-organ migratory T cells (TIM cells). TIM cells move from the BM to the intestine by upregulating integrin ß7 and downregulating C-X-C motif chemokine receptor 3 during leukaemogenesis. Upon immunogenic chemotherapy, these BM-derived TIM cells return from the intestine to the BM through integrin α4-vascular cell adhesion molecule 1 interaction. Blocking C-X-C motif chemokine receptor 3 function boosts the immune response against leukaemia by enhancing T cell trafficking. This phenomenon can also be observed in patients with leukaemia. In summary, we identify an unrecognized intestine-BM trafficking circuit of T cells that contributes to the antitumour effects of immunogenic chemotherapy.

2.
Immunol Res ; 2024 Jul 16.
Artículo en Inglés | MEDLINE | ID: mdl-39009881

RESUMEN

Rheumatoid arthritis (RA) is a chronic, inflammatory, systemic autoimmune disease characterized by cartilage, bone damage, synovial inflammation, hyperplasia, autoantibody production, and systemic features. To obtain an overall profile of the immune environment in RA patients and its association with clinical features, we performed single-cell transcriptome and T-cell receptor sequencing of mononuclear cells from peripheral blood (PBMC) and synovial fluid (SF) from RA patients, integrated with two large cohorts with bulk RNA sequencing for further validation and investigation. Dendritic cells (DCs) exhibited relatively high functional heterogeneity and tissue specificity in relation to both antigen presentation and proinflammatory functions. Peripheral helper T cells (TPHs) are likely to originate from synovial tissue, undergo activation and exhaustion, and are subsequently released into the peripheral blood. Notably, among all immune cell types, TPHs were found to have the most intense associations with disease activity. In addition, CD8 effector T cells could be clustered into two groups with different cytokine expressions and play distinct roles in RA development. By integrating single-cell data with bulk sequencing from two large cohorts, we identified interactions among TPHs, CD8 cells, CD16 monocytes, and DCs that strongly contribute to the proinflammatory local environment in RA joints. Of note, the swollen 28-joint counts exhibited a more pronounced association with this immune environment compared to other disease activity indexes. The immune environment alternated significantly from PBMCs to SF, which indicated that a series of immune cells was involved in proinflammatory responses in the local joints of RA patients. By integrating single-cell data with two large cohorts, we have uncovered associations between specific immune cell populations and clinical features. This integration provides a rapid and precise methodology for assessing local immune activation, offering valuable insights into the pathophysiological mechanisms at play in RA.

3.
Metab Eng ; 84: 95-108, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38901556

RESUMEN

Microbial instability is a common problem during bio-production based on microbial hosts. Halomonas bluephagenesis has been developed as a chassis for next generation industrial biotechnology (NGIB) under open and unsterile conditions. However, the hidden genomic information and peculiar metabolism have significantly hampered its deep exploitation for cell-factory engineering. Based on the freshly completed genome sequence of H. bluephagenesis TD01, which reveals 1889 biological process-associated genes grouped into 84 GO-slim terms. An enzyme constrained genome-scale metabolic model Halo-ecGEM was constructed, which showed strong ability to simulate fed-batch fermentations. A visible salt-stress responsive landscape was achieved by combining GO-slim term enrichment and CVT-based omics profiling, demonstrating that cells deploy most of the protein resources by force to support the essential activity of translation and protein metabolism when exposed to salt stress. Under the guidance of Halo-ecGEM, eight transposases were deleted, leading to a significantly enhanced stability for its growth and bioproduction of various polyhydroxyalkanoates (PHA) including 3-hydroxybutyrate (3HB) homopolymer PHB, 3HB and 3-hydroxyvalerate (3HV) copolymer PHBV, as well as 3HB and 4-hydroxyvalerate (4HB) copolymer P34HB. This study sheds new light on the metabolic characteristics and stress-response landscape of H. bluephagenesis, achieving for the first time to construct a long-term growth stable chassis for industrial applications. For the first time, it was demonstrated that genome encoded transposons are the reason for microbial instability during growth in flasks and fermentors.


Asunto(s)
Halomonas , Halomonas/genética , Halomonas/metabolismo , Halomonas/enzimología , Halomonas/crecimiento & desarrollo , Ingeniería Metabólica , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Redes y Vías Metabólicas/genética , Eliminación de Gen , Modelos Biológicos
4.
Appl Opt ; 63(11): 2822-2830, 2024 Apr 10.
Artículo en Inglés | MEDLINE | ID: mdl-38856377

RESUMEN

Local phase retardation (LPR) is increasingly recognized as a crucial biomarker for assessing disease progression. However, the presence of speckle noise significantly challenges its accuracy and polarization contrast. To address this challenge, we propose a signal-processing strategy aimed at reducing the impact of noise on LPR measurements. In this approach, the LPR is reconstructed by polar decomposition after averaging multiple Mueller matrices from different overlapping sub-spectra. To optimize measurement accuracy, we systematically combined and traversed different sub-spectral numbers and bandwidths. By examining the quarter-wave plate and glass slide, high-accuracy phase retardation measurements were successfully verified, and the maximum polarization contrast was improved by 23%. Moreover, experimental results from multi-tissue imaging vividly illustrate that the equivalent number of looks (ENL) and polarization contrast were improved by 18% and 19%, respectively. This outcome indicates that our proposed strategy can effectively reduce the noise spikes, enhancing tissue discrimination capabilities.

5.
Cell Rep Med ; 5(5): 101536, 2024 May 21.
Artículo en Inglés | MEDLINE | ID: mdl-38697103

RESUMEN

Spatial transcriptomics (ST) provides insights into the tumor microenvironment (TME), which is closely associated with cancer prognosis, but ST has limited clinical availability. In this study, we provide a powerful deep learning system to augment TME information based on histological images for patients without ST data, thereby empowering precise cancer prognosis. The system provides two connections to bridge existing gaps. The first is the integrated graph and image deep learning (IGI-DL) model, which predicts ST expression based on histological images with a 0.171 increase in mean correlation across three cancer types compared with five existing methods. The second connection is the cancer prognosis prediction model, based on TME depicted by spatial gene expression. Our survival model, using graphs with predicted ST features, achieves superior accuracy with a concordance index of 0.747 and 0.725 for The Cancer Genome Atlas breast cancer and colorectal cancer cohorts, outperforming other survival models. For the external Molecular and Cellular Oncology colorectal cancer cohort, our survival model maintains a stable advantage.


Asunto(s)
Aprendizaje Profundo , Neoplasias , Microambiente Tumoral , Humanos , Pronóstico , Neoplasias/patología , Neoplasias/genética , Neoplasias/diagnóstico , Transcriptoma/genética , Regulación Neoplásica de la Expresión Génica , Femenino , Neoplasias de la Mama/patología , Neoplasias de la Mama/genética , Neoplasias de la Mama/diagnóstico
6.
BMC Gastroenterol ; 24(1): 180, 2024 May 22.
Artículo en Inglés | MEDLINE | ID: mdl-38778288

RESUMEN

BACKGROUND: Intussusception presents a significant emergency that often necessitates bowel resection, leading to severe complications and management challenges. This study aims to investigate and establish a scoring system to enhance the prediction of bowel resection necessity in pediatric intussusception patients. METHODS: This retrospective study analyzed 660 hospitalized patients with intussusception who underwent surgical management at a pediatric hospital in Southwest China from April 2008 to December 2020. The necessity of bowel resection was assessed and categorized in this cohort. Variables associated with bowel resection were examined using univariate and multivariate logistic regression analyses. Based on these analyses, a scoring system was developed, grounded on the summation of the coefficients (ß). RESULTS: Among the 660 patients meeting the inclusion criteria, 218 required bowel resection during surgery. Bowel resection occurrence was linked to an extended duration of symptoms (Odds Ratio [OR] = 2.14; 95% Confidence Interval [CI], 1.03-5.23; P = 0.0015), the presence of gross bloody stool (OR = 8.98; 95% CI, 1.76-48.75, P < 0.001), elevated C-reactive protein levels (OR = 4.79; 95% CI, 1.12-28.31, P = 0.0072), lactate clearance rate (LCR) (OR = 17.25; 95% CI, 2.36-80.35; P < 0.001), and the intussusception location (OR = 12.65; 95% CI, 1.46-62.67, P < 0.001), as determined by multivariate logistic regression analysis. A scoring system (totaling 14.02 points) was developed from the cumulative ß coefficients, with a threshold of 5.22 effectively differentiating infants requiring surgical intervention from others with necrotizing enterocolitis (NEC), exhibiting a sensitivity of 78.3% and a specificity of 71.9%. CONCLUSIONS: This study successfully identified multiple risk factors for bowel resection and effectively used a scoring system to identify patients for optimal clinical management.


Asunto(s)
Intususcepción , Humanos , Intususcepción/cirugía , Intususcepción/diagnóstico , Estudios Retrospectivos , Masculino , Femenino , Lactante , Preescolar , China , Proteína C-Reactiva/análisis , Procedimientos Quirúrgicos del Sistema Digestivo/métodos , Modelos Logísticos , Niño , Factores de Riesgo
7.
Oncogene ; 43(24): 1836-1851, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38654108

RESUMEN

Vascular endothelial cells (VECs) are key players in the formation of neovessels and tumor metastasis, the ultimate cause of the majority of cancer-related human death. However, the crosstalk between VECs and metastasis remain greatly elusive. Based on our finding that tumor-associated VECs present significant decrease of Nrdp1 protein which is closely correlated with higher metastatic probability, herein we show that the conditional medium from hypoxia-incubated cancer cells induces extensive Nrdp1 downregulation in human and mouse VECs by vascular endothelial growth factor (VEGF), which activates CHIP, followed by Nrdp1 degradation in ubiquitin-proteasome-dependent way. More importantly, lung metastases of cancer cells significantly increase in conditional VECs Nrdp1 knockout mice. Mechanically, Nrdp1 promotes degradation of Fam20C, a secretory kinase involved in phosphorylating numerous secreted proteins. Reciprocally, deficiency of Nrdp1 in VECs (ecNrdp1) results in increased secretion of Fam20C, which induces degradation of extracellular matrix and disrupts integrity of vascular basement membrane, thus driving tumor metastatic dissemination. In addition, specific overexpression of ecNrdp1 by Nrdp1-carrying adeno-associated virus or chemical Nrdp1 activator ABPN efficiently mitigates tumor metastasis in mice. Collectively, we explore a new mechanism for VEGF to enhance metastasis and role of Nrdp1 in maintaining the integrity of vascular endothelium, suggesting that ecNrdp1-mediated signaling pathways might become potential target for anti-metastatic therapies.


Asunto(s)
Membrana Basal , Células Endoteliales , Ratones Noqueados , Metástasis de la Neoplasia , Factor A de Crecimiento Endotelial Vascular , Animales , Humanos , Ratones , Membrana Basal/metabolismo , Membrana Basal/patología , Línea Celular Tumoral , Células Endoteliales/metabolismo , Células Endoteliales/patología , Neoplasias Pulmonares/secundario , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/genética , Ubiquitina-Proteína Ligasas/metabolismo , Ubiquitina-Proteína Ligasas/genética , Factor A de Crecimiento Endotelial Vascular/metabolismo , Factor A de Crecimiento Endotelial Vascular/genética
8.
Chin J Integr Med ; 2024 Apr 02.
Artículo en Inglés | MEDLINE | ID: mdl-38561489

RESUMEN

Prostate cancer is a prevalent and debilitating disease that necessitates effective prevention and treatment strategies. Green tea, a well-known beverage derived from the Camellia sinensis plant, contains bioactive compounds with potential health benefits, including catechins and polyphenols. This comprehensive review aims to explore the potential benefits of green tea in prostate cancer prevention and treatment by examining existing literature. Green tea possesses antioxidant, anti-inflammatory, and anti-carcinogenic properties attributed to its catechins, particularly epigallocatechin gallate. Epidemiological studies have reported an inverse association between green tea consumption and prostate cancer risk, with potential protection against aggressive forms of the disease. Laboratory studies demonstrate that green tea components inhibit tumor growth, induce apoptosis, and modulate signaling pathways critical to prostate cancer development and progression. Clinical trials and human studies further support the potential benefits of green tea. Green tea consumption has been found to be associated with a reduction in prostate-specific antigen levels, tumor markers, and played a potential role in slowing disease progression. However, challenges remain, including optimal dosage determination, formulation standardization, and conducting large-scale, long-term clinical trials. The review suggests future research should focus on combinatorial approaches with conventional therapies and personalized medicine strategies to identify patient subgroups most likely to benefit from green tea interventions.

9.
Langmuir ; 40(16): 8665-8677, 2024 Apr 23.
Artículo en Inglés | MEDLINE | ID: mdl-38598258

RESUMEN

In this study, a simple, green, and low-cost room temperature synthesis of broccoli-like silver nanoflowers (AgNF) with a particle size of about 300-500 nm was developed using plant-derived caffeic acid as a reducing agent and polyvinylpyrrolidone as a dispersant under ultrasound assistance. The flower clusters covered by small nanocrystals of 20-50 nm significantly enhance the electromagnetic field signals. AgNF was deposited on the surface of silicon wafers as a surface-enhanced Raman spectroscopy sensor for the detection of probe molecules such as rhodamine 6G (R6G) and malachite green with high sensitivity, homogeneity, and reproducibility. AgNF was deposited on cotton fabrics in the form of composites to catalyze the degradation of dye pollutants such as R6G, MG, and methyl orange in the presence of sodium borohydride. 0.1 g of AgNF/cotton fabric could assist 15 mmol/L NaBH4 to achieve over 90% degradation of various dyes as well as a high concentration of dyes in 12 min with good reusability and recyclability. The AgNF synthesized in this work can not only monitor the type and amounts of pollutants (dyes) in wastewater but also catalyze the rapid degradation of dyes, which is expected to be valuable for industrial applications.

10.
Materials (Basel) ; 17(5)2024 Mar 06.
Artículo en Inglés | MEDLINE | ID: mdl-38473686

RESUMEN

Synthetic dyes are prone to water pollution during use, jeopardizing biodiversity and human health. This study aimed to investigate the adsorption and photocatalytic assist potential of sodium lignosulfonate (LS) in in situ reduced silver nanoparticles (AgNPs) and chitosan (CS)-loaded silver nanoparticles (CS-LS/AgNPs) as adsorbents for Rhodamine B (RhB). The AgNPs were synthesized by doping LS on the surface of chitosan for modification. Fourier transform infrared (FT-IR) spectrometry, energy-dispersive spectroscopy (EDS), scanning electron microscopy (SEM), X-ray diffraction (XRD), and X-ray photoelectron spectroscopy (XPS) were used to confirm the synthesis of nanomaterials. The adsorption and photocatalytic removal experiments of RhB were carried out under optimal conditions (initial dye concentration of 20 mg/L, adsorbent dosage of 0.02 g, time of 60 min, and UV power of 250 W), and the kinetics of dye degradation was also investigated, which showed that the removal rate of RhB by AgNPs photocatalysis can reach 55%. The results indicated that LS was highly effective as a reducing agent for the large-scale production of metal nanoparticles and can be used for dye decolorization. This work provides a new catalyst for the effective removal of dye from wastewater, and can achieve high-value applications of chitosan and lignin.

11.
Langmuir ; 40(13): 7147-7157, 2024 Apr 02.
Artículo en Inglés | MEDLINE | ID: mdl-38520353

RESUMEN

In this work, sea urchin-like magnetic Fe3O4@CA/BNNS/AgNP composite microspheres were successfully prepared. The photocatalytic performance of composite microspheres for the organic dye rhodamine B (RhB) was systematically investigated under different conditions, and the catalytic degradation rate of RhB was as high as 95% within 60 min; after three cycles of recycling, the degradation rate of RhB was reduced by only 8%. The main active agents in the reaction are e- and •O2-. Fe3O4@CA/BNNS/AgNP microspheres prepared in this study exhibit photocatalytic and electrochemical properties, making them easy to separate. This work is not limited to the development of Fe3O4-based catalysts but also is expected to provide ideas for the research and progress of photocatalytic composite catalysts with electrochemical properties.

12.
Int J Biol Macromol ; 266(Pt 1): 131140, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38537864

RESUMEN

Conventional textile dyeing relies on the use of dyes and pigments, which can cause severe environmental contamination and waste a large amount of water. Structural coloring is one of the effective ways to achieve environmentally friendly coloring of textiles. In this work, three plant polyphenols with the same o-benzenetriol structure (tannic acid (TA), gallic acid (GA), and tea polyphenol (TP)) were selected as raw materials. Three plant polyphenols can quickly form nanofilms at the gas-liquid interface through a Schiff base reaction with polyethyleneimine (PEI) under mildly alkaline conditions, which were deposited to the surface of silk fabric, allowing precise control over the thickness of film by adjusting the time, resulting in various structurally colored silk fabric. This method for creating structural colors is not substrate-specific and enables the quick production of structural colors on various textile substrates. Furthermore, the structural color silk fabric based on plant polyphenol has antibacterial performance. This textile coloring method is simple, cost-effective and environmentally friendly, providing a new approach to eco-friendly textile dyeing.


Asunto(s)
Color , Polifenoles , Seda , Textiles , Polifenoles/química , Seda/química , Colorantes/química , Antibacterianos/química , Antibacterianos/farmacología
13.
Int J Gen Med ; 17: 693-704, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38435112

RESUMEN

Background: Discordance between the anatomy and physiology of the coronary has important implications for managing patients with stable coronary disease, but its significance in ST-elevation myocardial infarction has not been fully elucidated. Methods: The retrospective study involved patients diagnosed with ST-elevation myocardial infarction (STEMI) who underwent percutaneous coronary intervention (PCI), along with quantitative coronary angiography (QCA) and quantitative flow ratio (QFR) assessments. Patients were stratified into four groups regarding the severity of the culprit vessel, both visually and functionally: concordantly negative (QCA-diameter stenosis [DS] ≤ 50% and QFR > 0.80), mismatch (QCA-DS > 50% and QFR > 0.80), reverse mismatch (QCA-DS ≤ 50% and QFR ≤ 0.80), and concordantly positive (QCA-DS > 50% and QFR ≤ 0.80). Multivariable logistic regression analyses were conducted to identify the clinical factors linked to visual-functional mismatches. Kaplan‒Meier analysis was conducted to estimate the 18-month adverse cardiovascular events (MACE)-free survival between the four groups. Results: The study involved 310 patients, with 68 presenting visual-functional mismatch, and 51 exhibiting reverse mismatch. The mismatch was associated with higher angiography-derived microcirculatory resistance (AMR) (adjusted odds ratio [aOR]=1.016, 95% CI: 1.010-1.022, P<0.001). Reverse mismatch was associated with larger area stenosis (aOR=1.044, 95% CI: 1.004-1.086, P=0.032), lower coronary flow velocity (aOR=0.690, 95% CI: 0.567-0.970, P<0.001) and lower AMR (aOR=0.947, 95% CI: 0.924-0.970, P<0.001). Additionally, the mismatch group showed the worst 18-month MACE-free survival among the four groups (Log rank test p = 0.013). Conclusion: AMR plays a significant role in the occurrence of visual-functional mismatches between QCA-DS and QFR, and the mismatch group showed the worst prognosis.

14.
Nanoscale Adv ; 6(3): 876-891, 2024 Jan 30.
Artículo en Inglés | MEDLINE | ID: mdl-38298577

RESUMEN

In this research, a molecular dynamics (MD) model was adopted to investigate the essence of the effect of strain rate on the mechanical behavior of the Fe14.6Ni (at%) elastocaloric refrigeration alloy. The study showed that the mechanical behavior of the Fe14.6Ni (at%) alloy was dependent on the strain rate. Besides, the investigation of temperature demonstrated that the strain rate influenced mechanical behavior by changing the transient temperatures. Furthermore, it was found that the adiabatic temperature change (ΔTadi) was high and up to 51 K, which was a 1.57 times improvement. Finally, the conclusion was drawn that the strain rate influenced the mechanical behavior by changing the transient total kinetic energy and the phase content evolution processes, which was the essence of the effect of strain rate on the mechanical behavior. This work has clarified the essence and enriched the theory of the effect of strain rate on the mechanical behavior of elastocaloric refrigeration alloys.

15.
ACS Nano ; 2024 Feb 07.
Artículo en Inglés | MEDLINE | ID: mdl-38323542

RESUMEN

Autoimmune diseases, allergies, transplant rejections, generation of antidrug antibodies, and chronic inflammatory diseases have impacted a large group of people across the globe. Conventional treatments and therapies often use systemic or broad immunosuppression with serious efficacy and safety issues. Tolerogenic vaccines represent a concept that has been extended from their traditional immune-modulating function to induction of antigen-specific tolerance through the generation of regulatory T cells. Without impairing immune homeostasis, tolerogenic vaccines dampen inflammation and induce tolerogenic regulation. However, achieving the desired potency of tolerogenic vaccines as preventive and therapeutic modalities calls for precise manipulation of the immune microenvironment and control over the tolerogenic responses against the autoantigens, allergens, and/or alloantigens. Engineered nano-/microparticles possess desirable design features that can bolster targeted immune regulation and enhance the induction of antigen-specific tolerance. Thus, particle-based tolerogenic vaccines hold great promise in clinical translation for future treatment of aforementioned immune disorders. In this review, we highlight the main strategies to employ particles as exciting tolerogenic vaccines, with a focus on the particles' role in facilitating the induction of antigen-specific tolerance. We describe the particle design features that facilitate their usage and discuss the challenges and opportunities for designing next-generation particle-based tolerogenic vaccines with robust efficacy to promote antigen-specific tolerance for immunotherapy.

16.
Metab Eng ; 82: 238-249, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38401747

RESUMEN

Ectoine, a crucial osmoprotectant for salt adaptation in halophiles, has gained growing interest in cosmetics and medical industries. However, its production remains challenged by stringent fermentation process in model microorganisms and low production level in its native producers. Here, we systematically engineered the native ectoine producer Halomonas bluephagenesis for ectoine production by overexpressing ectABC operon, increasing precursors availability, enhancing product transport system and optimizing its growth medium. The final engineered H. bluephagenesis produced 85 g/L ectoine in 52 h under open unsterile incubation in a 7 L bioreactor in the absence of plasmid, antibiotic or inducer. Furthermore, it was successfully demonstrated the feasibility of decoupling salt concentration with ectoine synthesis and co-production with bioplastic P(3HB-co-4HB) by the engineered H. bluephagenesis. The unsterile fermentation process and significantly increased ectoine titer indicate that H. bluephagenesis as the chassis of Next-Generation Industrial Biotechnology (NGIB), is promising for the biomanufacturing of not only intracellular bioplastic PHA but also small molecular compound such as ectoine.


Asunto(s)
Aminoácidos Diaminos , Halomonas , Halomonas/genética , Aminoácidos Diaminos/genética , Antibacterianos , Biopolímeros
17.
Cell Death Dis ; 15(2): 168, 2024 Feb 23.
Artículo en Inglés | MEDLINE | ID: mdl-38395990

RESUMEN

Glioblastoma (GBM) cells require large amounts of iron for tumor growth and progression, which makes these cells vulnerable to destruction via ferroptosis induction. Mitochondria are critical for iron metabolism and ferroptosis. Sirtuin-3 (SIRT3) is a deacetylase found in mitochondria that regulates mitochondrial quality and function. This study aimed to characterize SIRT3 expression and activity in GBM and investigate the potential therapeutic effects of targeting SIRT3 while also inducing ferroptosis in these cells. We first found that SIRT3 expression was higher in GBM tissues than in normal brain tissues and that SIRT3 protein expression was upregulated during RAS-selective lethal 3 (RSL3)-induced GBM cell ferroptosis. We then observed that inhibition of SIRT3 expression and activity in GBM cells sensitized GBM cells to RSL3-induced ferroptosis both in vitro and in vivo. Mechanistically, SIRT3 inhibition led to ferrous iron and ROS accumulation in the mitochondria, which triggered mitophagy. RNA-Sequencing analysis revealed that upon SIRT3 knockdown in GBM cells, the mitophagy pathway was upregulated and SLC7A11, a critical antagonist of ferroptosis via cellular import of cystine for glutathione (GSH) synthesis, was downregulated. Forced expression of SLC7A11 in GBM cells with SIRT3 knockdown restored cellular cystine uptake and consequently the cellular GSH level, thereby partially rescuing cell viability upon RSL3 treatment. Furthermore, in GBM cells, SIRT3 regulated SLC7A11 transcription through ATF4. Overall, our study results elucidated novel mechanisms underlying the ability of SIRT3 to protect GBM from ferroptosis and provided insight into a potential combinatorial approach of targeting SIRT3 and inducing ferroptosis for GBM treatment.


Asunto(s)
Ferroptosis , Glioblastoma , Sirtuina 3 , Humanos , Sistema de Transporte de Aminoácidos y+/genética , Cistina , Ferroptosis/genética , Glioblastoma/genética , Glutatión , Indanos , Hierro , Mitofagia , Sirtuina 3/genética
18.
Sci Rep ; 14(1): 4745, 2024 02 27.
Artículo en Inglés | MEDLINE | ID: mdl-38413652

RESUMEN

To compare the safety and effectiveness of the combination of intelligent intrarenal pressure control platforms (IPCP) and flexible ureteral access sheath (FUAS) combined with retrograde intrarenal surgery (RIRS) for the treatment of renal stones less than 2 cm. We retrospectively collected 383 patients with renal stones who underwent RIRS in our department from June 2022 to October 2023. Inclusion criteria: stone length or the sum of multiple stone lengths ≤ 2 cm. Finally, 99 cases were included and divided into an IPCP group (n = 40) and FUAS group (n = 59) based on surgical methods. The main endpoint was the stone-free rate (SFR) at third months after surgery, with no residual stones or stone fragments less than 2 mm defined as stone clearance. The secondary endpoints were surgical time and perioperative complications, including fever, sepsis, septic shock, and perirenal hematoma. There was no statistically significant difference in general information between the two groups, including age, gender, body mass index, comorbidities, stone side, stone location, stone length, urine bacterial culture, and hydronephrosis. The operation time for IPCP group and FUAS group was 56.83 ± 21.33 vs 55.47 ± 19.69 min (p = 0.747). The SFR of IPCP group and FUAS group on the first postoperative day was 75.00% vs 91.50% (p = 0.024). The SFR was 90.00% vs 94.90% in the third month (p = 0.349).In IPCP group, there were 11 cases with stones located in the lower renal calyces and 17 cases in FUAS group. The SFR of the two groups on the first day and third months after surgery were 45.50% vs 88.20% (p = 0.014) and 63.60% vs 94.10% (p = 0.040), respectively, with statistical differences. For kidney stones ≤ 2 cm, there was no difference in SFR and the incidence of infection-related complications between IPCP and FUAS combined with RIRS, both of which were superior to T-RIRS. For lower renal caliceal stones, FUAS has a higher SFR compared to IPCP.


Asunto(s)
Difosfonatos , Cálculos Renales , Ureteroscopía , Humanos , Ureteroscopía/efectos adversos , Ureteroscopía/métodos , Estudios Retrospectivos , Resultado del Tratamiento , Cálculos Renales/cirugía
19.
J Clin Neurosci ; 121: 11-17, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38308978

RESUMEN

BACKGROUND: Nervus intermedius neuralgia (NIN) is characterized by paroxysmal episodes of sharp, lancinating pain in the deep ear. Unfortunately, only a few studies exist in the literature on this pain syndrome, its pathology and postoperative outcomes. METHOD: We conducted a retrospective review of four cases diagnosed with NIN who underwent a neurosurgical intervention at our center from January 2015 to January 2023. Detailed information on their MRI examinations, intraoperative findings and other clinical presentations were obtained, and the glossopharyngeal and vagus nerves were isolated for immunohistochemistry examination. RESULTS: A total of 4 NIN patients who underwent a microsurgical intervention at our institution were included in this report. The NI was sectioned in all patients and 3 of them underwent a microvascular decompression. Of these 4 patients, 1 had a concomitant trigeminal neuralgia (TN), and 1 a concomitant glossopharyngeal neuralgia (GPN). Three patients underwent treatment for TN and 2 for GPN. Follow-up assessments ranged from 8 to 99 months. Three patients reported complete pain relief immediately after the surgery until last follow-up, while in the remaining patient the preoperative pain gradually resolved over the 3 month period. Immunohistochemistry revealed that a greater amount of CD4+ and CD8+ T cells had infiltrated the glossopharyngeal versus vagus nerve. CONCLUSIONS: NIN is an extremely rare condition showing a high degree of overlap with TN/GPN. An in depth neurosurgical intervention is effective to completely relieve NIN pain, without any serious complications. It appears that T cells may play regulatory role in the pathophysiology of CN neuralgia.


Asunto(s)
Enfermedades del Nervio Glosofaríngeo , Cirugía para Descompresión Microvascular , Neuralgia , Neuralgia del Trigémino , Humanos , Nervio Facial , Linfocitos T CD8-positivos , Neuralgia/etiología , Neuralgia/cirugía , Neuralgia del Trigémino/diagnóstico por imagen , Neuralgia del Trigémino/etiología , Neuralgia del Trigémino/cirugía , Enfermedades del Nervio Glosofaríngeo/cirugía , Resultado del Tratamiento
20.
Biomimetics (Basel) ; 9(1)2024 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-38248589

RESUMEN

Traditional textile dyeing uses chemical pigments and dyes, which consumes a large amount of water and causes serious environmental pollution. Structural color is an essential means of achieving green dyeing of textiles, and thin-film interference is one of the principles of structural coloring. In the assembly of structural color films, it is necessary to introduce dark materials to suppress light scattering and improve the brightness of the fabric. In this study, the conditions for the generation of nanofilms of catechin (CC) at the gas-liquid interface were successfully investigated. At the same time, environmentally friendly colored silk fabrics were novelly prepared using polycatechin (PCC) structural color films. In addition, it was found that various structural colors were obtained on the surface of silk fabrics by adjusting the time. Meanwhile, the color fastness of the structural colored fabrics was improved by introducing polyvinylpyrrolidone (PVP) to form a strong hydrogen bond between the fabric and catechin. PCC film is uniform and smooth, with a special double-layer structure, and can be attached to the surface of silk fabrics, giving the fabrics special structural colors. Through the thin-film interference formed between the visible light and the PCC film, the silk fabrics obtain bright, controllable, and uniform structural colors. This method is easy to operate and provides a new way of thinking for environmental-protection-oriented coloring of fabrics.

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