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2.
Nano Lett ; 2024 Jun 10.
Artículo en Inglés | MEDLINE | ID: mdl-38856668

RESUMEN

Cell membrane-based nanovesicles (CMNVs) play pivotal roles in biomolecular transportation in living organisms and appear as attractive bioinformed nanomaterials for theranostic applications. However, the current surface-engineering technologies are limited in flexibility and orthogonality, making it challenging to simultaneously display multiple different ligands on the CMNV surface in a precisely controlled manner. Here, we developed a DNA scaffold-programmed approach to orthogonally engineer CMNVs with versatile ligands. The designed DNA scaffolds can rapidly anchor onto the CMNV surface, and their unique sequences and hybridized properties enable independent control of the loading of multiple different types of biomolecules on the CMNVs. As a result, the orthogonal engineering of CMNVs with a renal targeted peptide and a therapeutic protein at controlled ratios demonstrated an enhanced renal targeting and repair potential in vivo. This study highlights that a DNA scaffold-programmed platform can provide a potent means for orthogonal and flexible surface engineering of CMNVs for diverse therapeutic purposes.

3.
Opt Express ; 32(5): 7448-7462, 2024 Feb 26.
Artículo en Inglés | MEDLINE | ID: mdl-38439424

RESUMEN

Optofluidic systems, integrating microfluidic and micro-optical technologies, have emerged as transformative tools for various applications, from molecular detection to flow cytometry. However, existing optofluidic microlenses often rely on external forces for tunability, hindering seamless integration into systems. This work presents an approach using two-photon polymerization (TPP) to fabricate inherently tunable microlens arrays, eliminating the need for supplementary equipment. The optofluidic design incorporates a three-layered structure enabling dynamic manipulation of refractive indices within microchannels, leading to tunable focusing characteristics. It is shown that the TPP fabricated optofluidic microlenses exhibit inherent tunable focal lengths, numerical apertures, and spot sizes without reliance on external forces. This work signifies some advancements in optofluidic technology, offering precise and tunable microlenses with potential applications in adaptive imaging and variable focal length microscopy.

4.
Front Pediatr ; 12: 1351401, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38384661

RESUMEN

Background: The present systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted to investigate the effects of music on pain management in preterm neonates during painful procedures. Methods: The PubMed, Embase, Web of Science, EBSCO and Cochrane Library databases were searched to identify relevant articles published from their inception to September 2023. The study search strategy and all other processes were implemented in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Results: Four RCTs that satisfied the inclusion criteria were included in this meta-analysis. The music group had significantly lower Premature Infant Pain Profile (PIPP) scores during (RR = -1.21; 95% CI = -2.02--0.40, p = 0.0032) and after painful procedures (RR = -0.65; 95% CI = -1.06--0.23, p = 0.002). The music group showed fewer changes in PIPP scores after invasive operations than did the control group (RR = -2.06; 95% CI -3.16--0.96; p = 0.0002). Moreover, our results showed that music improved oxygen saturation during (RR = 3.04, 95% CI = 1.64-4.44, p < 0.0001) and after painful procedures (RR = 3.50, 95% CI = 2.11-4.90, p < 0.00001). However, the change in peak heart rate during and after painful procedures was not statistically significant (RR = -12.14; 95% CI = -29.70-5.41 p = 0.18; RR = -10.41; 95% CI = -22.72-1.90 p = 0.10). Conclusion: In conclusion, this systematic review demonstrated that music interventions are effective for relieving procedural pain in preterm infants. Our results indicate that music can reduce stress levels and improve blood oxygen saturation. Due to the current limitations, large-scale, prospective RCTs should be performed to validate the present results.

5.
J Org Chem ; 89(6): 3941-3953, 2024 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-38421294

RESUMEN

An efficient synthetic method for constructing 2,3- and 2,4-disubstituted pyrimidio[1,2-b]indazole skeletons through I2-DMSO-mediated and substrate-controlled regioselective [4 + 2] cyclization is reported. The reaction conditions are mild, its operation is simple, and the substrate scope is wide. More than 60 pyrimidio[1,2-b]indazole derivatives have been synthesized, providing a new methodology for constructing related molecules and potentially enriching bioactive-molecule libraries.

6.
Orthop Surg ; 16(3): 637-653, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38326289

RESUMEN

OBJECTIVE: Three-dimensional (3D)-CT data is currently insufficient for classifying femoral trochanter fractures. Fracture classification based on fracture stability analysis is helpful to evaluate the prognosis of patients after internal fixation. Currently, there is a lack of fracture classification methods based on 3D-CT images and fracture stability analysis. The aim of this study was to propose a new six-part classification method for intertrochanteric fractures of femur based on 3D-CT images and fracture stability analysis to improve the diagnosis rate of unstable fractures. METHOD: From January 2009 to December 2019, 320 patients receiving intramedullary nail surgery for femoral intertrochanteric fractures at Chengdu University's Affiliated Hospital were studied retrospectively. AO and six-part classifications were undertaken according to the 3D-CT image data of the patients, and the stability rates of two classifications were compared. According to the six-part classification stability criteria, the patients were divided into a stable and an unstable fracture group. The perioperative and follow-up indicators of the two groups were statistically analyzed, and the six-part classification's inter-observer and internal reliability was examined. RESULTS: There were 107 men and 213 females women the 320 patients, with an average age of 79.32 ± 11.26 years and an osteoporosis rate of 55.63% (178/320). The fracture stability rate of 39.69% (127/320) was studied using a six-part classification method. The AO classification fracture stability rate was 42.50% (136/320), with no significant difference (χ2 = 0.523, p = 0.470 > 0.05). There is no statistically significant difference between the two classification techniques in the examination of fracture stability (McNemer difference test p = 0.306 > 0.05; Kappa consistency test p < 0.001). According to the six-part classification, fracture stability and instability group were divided into two groups. The following indicators were compared between the two groups: The surgery time (p = 0.280), fracture reduction quality (p = 0.062); function independent measurement (p = 0.075); timed up and go test (TUG) (p = 0.191), and Parker-Palmer score (p = 0.146). Were as compared according to the six-part classification of stable and unstable fracture groups. Perioperative blood loss (p < 0.001), the Harris score excellent and good rate (p = 0.043), fracture healing time (p < 0.001), and the entire weight-bearing duration (p = 0.002) were statistically significant. The difference in femoral head height (FHH) (p = 0.046), the change in femoral neck shaft angle (p = 0.003), the change in medial cephalic nail length (p = 0.033), and the change in tip-apex distance (TAD) (p = 0.002) were statistically significant compared to the relevant markers of imaging stability. Fracture stability had a substantial influence on Harris ratings at 3, 6, and 12 months following surgery, according to repeated measures analysis of variance (F(1,126) = 32.604, p < 0.001). The effect of time on the Harris score was similarly significant (F(1.893,238.508) = 202.771, p < 0.001). The observer intra-observer inter-group correlation coefficient (ICC) value was 0.941 > 0.75, the inter-observer ICC value was 0.921 > 0.75, and the intra-observer and inter-observer reliability were both good. CONCLUSION: The six-part classification of femoral intertrochanteric fractures based on 3D-CT images has broader guiding relevance for femoral intertrochanteric fracture stability analysis. Clinicians will find this classification simpler and more consistent than the AO classification.


Asunto(s)
Fracturas del Fémur , Fijación Intramedular de Fracturas , Fracturas de Cadera , Masculino , Humanos , Femenino , Anciano , Anciano de 80 o más Años , Fijación Intramedular de Fracturas/métodos , Estudios Retrospectivos , Reproducibilidad de los Resultados , Equilibrio Postural , Clavos Ortopédicos , Resultado del Tratamiento , Estudios de Tiempo y Movimiento , Fracturas del Fémur/cirugía , Fracturas de Cadera/diagnóstico por imagen , Fracturas de Cadera/cirugía , Cabeza Femoral
7.
Small ; 20(10): e2305594, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37919857

RESUMEN

Diabetic alveolar bone defect (DABD) causes persistent bacterial infection, prolonged inflammation, and delayed bone healing, making it a considerable clinical challenge. In this study, by integrating silver nanoclusters (AgNCs) and M2 macrophage-derived extracellular vesicles (M2EVs), a multifunctional DNA-based hydrogel, called Agevgel, is developed with antibacterial, anti-inflammatory, immunomodulatory, and osteogenic properties to promote DABD rebuilding. AgNCs are tightly embedded into the DNA scaffolds and exhibit effective anti-bacterial activity, while immunomodulatory M2EVs are encapsulated within the shape-variable DNA scaffolds and exhibit potent anti-inflammatory and osteogenic properties. The results reveal that Agevgel effectively prolongs the local retention time and bioactivity of M2EVs in vivo. In particular, the sustained release of M2EVs can last for at least 7 days when applying Agevgel to DABD. Compared to free M2EVs or Aggel (AgNCs encapsulated within the DNA hydrogel) treatments, the Agevgel treatment accelerates the defect healing rate of alveolar bone and dramatically improves the trabecular architecture. Mechanistically, Agevgel plays a key role in regulating macrophage polarization and promoting the expression of proliferative and osteogenic factors. In summary, Agevgel provides a comprehensive treatment strategy for DABD with a great clinical translational value, highlighting the application of DNA hydrogels as an ideal bioscaffolds for periodontal diseases.


Asunto(s)
Diabetes Mellitus , Procedimientos de Cirugía Plástica , Hidrogeles , Cicatrización de Heridas , Antibacterianos , ADN , Antiinflamatorios
8.
Int J Surg ; 110(3): 1770-1780, 2024 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-38126341

RESUMEN

BACKGROUND AND AIMS: Partial pancreatectomy, commonly used for chronic pancreatitis, or pancreatic lesions, has diverse impacts on endocrine and metabolism system. The study aims to determine the global prevalence of new-onset, worsening, and resolution of diabetes following partial pancreatectomy. METHODS: The authors searched PubMed, Embase, Web of Science, and Cochrane Library from inception to October, 2023. DerSimonian-Laird random-effects model with Logit transformation was used. Sensitivity analysis, meta-regression, and subgroup analysis were employed to investigate determinants of the prevalence of new-onset diabetes. RESULTS: A total of 82 studies involving 13 257 patients were included. The overall prevalence of new-onset diabetes after partial pancreatectomy was 17.1%. Univariate meta-regression indicated that study size was the cause of heterogeneity. Multivariable analysis suggested that income of country or area had the highest predictor importance (49.7%). For subgroup analysis, the prevalence of new-onset diabetes varied from 7.6% (France, 95% CI: 4.3-13.0) to 38.0% (UK, 95% CI: 28.2-48.8, P <0.01) across different countries. Patients with surgical indications for chronic pancreatitis exhibited a higher prevalence (30.7%, 95% CI: 21.8-41.3) than those with pancreatic lesions (16.4%, 95% CI: 14.3-18.7, P <0.01). The type of surgical procedure also influenced the prevalence, with distal pancreatectomy having the highest prevalence (23.7%, 95% CI: 22.2-25.3, P <0.01). Moreover, the prevalence of worsening and resolution of preoperative diabetes was 41.1 and 25.8%, respectively. CONCLUSIONS: Postoperative diabetes has a relatively high prevalence in patients undergoing partial pancreatectomy, which calls for attention and dedicated action from primary care physicians, specialists, and health policy makers alike.


Asunto(s)
Diabetes Mellitus , Neoplasias Pancreáticas , Pancreatitis Crónica , Humanos , Pancreatectomía/efectos adversos , Pancreatectomía/métodos , Diabetes Mellitus/epidemiología , Diabetes Mellitus/etiología , Diabetes Mellitus/cirugía , Páncreas/cirugía , Pancreatitis Crónica/epidemiología , Pancreatitis Crónica/cirugía , Pancreatitis Crónica/complicaciones , Neoplasias Pancreáticas/cirugía
9.
Opt Lett ; 48(21): 5603-5606, 2023 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-37910713

RESUMEN

Optofluidic chips are frequently utilized in applications such as biological observation, chemical detection, dynamic displays, imaging, holography, and sensing. Yet, developing continuously zoomable technology has been challenging in the production of optical devices. Using a spatial light modulator to shape a femtosecond laser to achieve multibeam parallel pulse punching, we propose an easy-to-fabricate, stable, and reliable tuning technique in this Letter. We then propose the addition of a liquid medium with a continuously variable refractive index to achieve controllable zooming without changing the position and morphology of the microlens. By pumping various concentrations of the liquid medium into the optofluidic chip, continuous tunability of the device was experimentally verified.

10.
Cell Mol Immunol ; 20(10): 1232-1250, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37644166

RESUMEN

SEL1L-mediated endoplasmic reticulum-associated degradation (ERAD) plays critical roles in controlling protein homeostasis by degrading misfolded or terminal unfolded proteins. However, it remains unclear how SEL1L regulates peripheral T-cell survival and homeostasis. Herein, we found that SEL1L deficiency led to a greatly reduced frequency and number of mature T cells, which was further validated by adoptive transfer experiments or bone marrow chimera experiments, accompanied by the induction of multiple forms of cell death. Furthermore, SEL1L deficiency selectively disrupted naïve CD8+ T-cell homeostasis, as indicated by the severe loss of the naïve T-cell subset but an increase in the memory T-cell subset. We also found that SEL1L deficiency fueled mTORC1/c-MYC activation and induced a metabolic shift, which was largely attributable to enhanced expression of the IL-15 receptor α and ß chains. Mechanistically, single-cell transcriptomic profiling and biochemical analyses further revealed that Sel1l-/- CD8+ T cells harbored excessive ER stress, particularly aberrant activation of the PERK-ATF4-CHOP-Bim pathway, which was alleviated by supplementing IL-7 or IL-15. Importantly, PERK inhibition greatly resolved the survival defects of Sel1l-/- CD8+ T cells. In addition, IRE1α deficiency decreased mTORC1 signaling in Sel1l-/- naïve CD8+ T cells by downregulating the IL-15 receptor α chain. Altogether, these observations suggest that the ERAD adaptor molecule SEL1L acts as an important checkpoint for preserving the survival and homeostasis of peripheral T cells by regulating the PERK signaling cascade and IL-15 receptor-mediated mTORC1 axis.


Asunto(s)
Degradación Asociada con el Retículo Endoplásmico , Proteínas Serina-Treonina Quinasas , Linfocitos T CD8-positivos/metabolismo , Supervivencia Celular , Endorribonucleasas/metabolismo , Homeostasis , Proteínas Serina-Treonina Quinasas/metabolismo , Ubiquitina-Proteína Ligasas/metabolismo , Animales , Ratones
11.
Anal Chem ; 95(23): 8850-8858, 2023 Jun 13.
Artículo en Inglés | MEDLINE | ID: mdl-37260159

RESUMEN

Micromixers are a critical component in microfluidics. However, most 2D passive micromixers produce optimal mixing at a high flow rate range and 3D micromixers require mm-scale channels or a complex assembly that is unsuitable for microfluidic applications. Here, we reported a 3D PDMS micromixer based on the splitting-stretching-recombination (SSR) of streams to facilitate molecular diffusion, which can effectively and rapidly mix solutions with low Reynolds numbers (0.01-10). The fabrication of our micromixer is convenient with only two steps─two-photon polymerization (2PP) 3D printing and soft lithography, with high resolution, reproducibility, and ease for integration. We investigated the mixing performance of the micromixer by CFD simulations and experimental studies under a confocal microscope; the results confirmed its better performance and higher chip miniaturization than others. It can achieve a mixing efficiency above 0.90 (which is generally regarded as complete mixing) for low-Re solutions (flow rates ≤60 µL/min) with a mixing volume smaller than 20 nL. The time for complete mixing is in the range of milliseconds (e.g., 21 ms for Re = 10, 194 ms for Re = 0.88). The device shows negligible degradation in mixing performance for highly viscous solutions (∼50 times more viscous than water), macromolecule solutions, and colloidal solutions of nanoparticles.

12.
Front Endocrinol (Lausanne) ; 14: 1170237, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37305058

RESUMEN

Diabetes mellitus (DM) is a systemic metabolic disease with high mortality and morbidity. Extracellular vesicles (EVs) have emerged as a novel class of signaling molecules, biomarkers and therapeutic agents. EVs-mediated intercellular and interorgan crosstalk of pancreatic islets plays a crucial role in the regulation of insulin secretion of ß-cells and insulin action in peripheral insulin target tissues, maintaining glucose homeostasis under physiological conditions, and it's also involved in pathological changes including autoimmune response, insulin resistance and ß-cell failure associated with DM. In addition, EVs may serve as biomarkers and therapeutic agents that respectively reflect the status and improve function and viability of pancreatic islets. In this review, we provide an overview of EVs, discuss EVs-mediated intercellular and interorgan crosstalk of pancreatic islet under physiological and diabetic conditions, and summarize the emerging applications of EVs in the diagnosis and treatment of DM. A better understanding of EVs-mediated intercellular and interorgan communication of pancreatic islets will broaden and enrich our knowledge of physiological homeostasis maintenance as well as the development, diagnosis and treatment of DM.


Asunto(s)
Diabetes Mellitus , Vesículas Extracelulares , Islotes Pancreáticos , Humanos , Fenómenos Fisiológicos Celulares , Insulina
13.
Water Sci Technol ; 87(3): 672-684, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36789711

RESUMEN

This study analyzed the removal effect of various doses of polyaluminum chloride (PACI) on wastewater treatment plants at pH 7. The sewage plant's secondary effluent organic matter (EfOM) separates into four components: hydrophobic base (HOB), hydrophilic (HI), hydrophobic acid (HOA), and hydrophobic neutral (HON). The removal effect for various forms of organic waste is optimum at 16 mg/L and that halogenated acetic acids (HAAs) and trihalomethanes (THMs) are formed simultaneously. After PACI treatment, hydrophobic organic compounds were converted to humic acid (HA), fulvic acid (FA), soluble microbial products (SMPs), and other HI organic compounds, increasing the amount of HAAs produced by HI fractions. Removal rate of hydrophobic organic compounds, particularly HON, is 92.8% when using PAC. Moreover, after EfOM coagulation, most HAAs are trichloroacetic acid (TCAA), followed by bromochloroacetic acid (BCAA) and bromodichloroacetic acid (BDCAA). Only HOB can produce monochloroacetic acid (MCAA), whereas HA and SMPs with HOA are primary components of dichloroacetic acid (DCAA). The toughest removable byproduct of THMs is CHBr3, and after condensation of each THM component, only HOA and HON produce CHBr3, while HI produces only a minimal quantity of CHBrCl2 and CHCl3.This finding is critical for understanding how disinfection byproducts are produced after chlorinating EfOM.


Asunto(s)
Contaminantes Químicos del Agua , Purificación del Agua , Trihalometanos/química , Agua , Desinfección , Acetatos , Contaminantes Químicos del Agua/química
14.
Biochim Biophys Acta Mol Cell Res ; 1870(3): 119414, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36535371

RESUMEN

Previous studies have shown that high levels of reactive oxygen species (ROS) and low tricarboxylic acid (TCA) activity in the brain promote pupal diapause, which is characterized by metabolic depression and lifespan extension. However, it is unclear whether ROS are associated with TCA activity. In this study, we demonstrate that ROS downregulate TCA activity and acetyl-CoA and pyruvate levels in the brains of diapause-destined pupae in the moth Helicoverpa armigera, as well as the protein levels of acetyl-CoA synthetase (ACS) and pyruvate kinase (PK), two proteins involved in the biosynthesis of acetyl-CoA and pyruvate, respectively. Interestingly, miR-34, which is highly expressed in the brains of diapause-destined pupae, can respond to ROS signaling. Furthermore, we show that miR-34 can reduce the expression of ACS and PK by directly targeting their mRNAs. Additionally, hypoxia-inducible factor (HIF), a transcription factor, can be activated by ROS and then promotes miR-34 transcription by binding a cis-element in its promoter. Moreover, we observed delayed pupal development after treatment with a ROS activator paraquat and a HIF activator dimethyloxallyl glycine. Taken together, these results suggest that a novel pathway ROS/HIF/miR-34/ACS-PK was found to negatively regulate TCA activity to promote insect diapause for lifespan extension.


Asunto(s)
MicroARNs , Mariposas Nocturnas , Animales , Piruvato Quinasa/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Longevidad/genética , Acetilcoenzima A/metabolismo , Mariposas Nocturnas/genética , Metabolismo Energético , Piruvatos/metabolismo , MicroARNs/genética , MicroARNs/metabolismo
15.
BMC Womens Health ; 22(1): 559, 2022 12 30.
Artículo en Inglés | MEDLINE | ID: mdl-36585693

RESUMEN

BACKGROUND: To investigate the positive rate and clinical applicability of liquid-based fungal method for detecting of vaginal fungi. We collect the secretions from the posterior vaginal fornix and the vaginal wall of 198 patients with clinically suspected fungi vaginitis patients for study. METHODS: The vaginal fungi of vaginal discharge were detected by fluorescence method, i.e., by liquid-based thin-layer fungi fluorescence morphology staining detection kit (liquid-based fungal method), saline smear method and fungal culture method. RESULTS: The positive rate of liquid-based fungal method, saline smear method was 50%, 25.75% respectively. The positive rate of liquid-based fungal method were 50%. The true positive rate of liquid-based fungal method (87.85%) was higher than that of saline smear method (45.79%, P < 0.001), which was easy to miss diagnosis. Moreover, the Kappa (K) of liquid-based fungal method was 0.81, and P < 0.01, which was statistically significant, indicating that the consistency of the two detection methods is good. Of the eight common symptoms of fungal vaginitis, the positive symptom coincidence rate of liquid-based fungal method was consistent with that of fungal culture method. It was also easier to see fungi under a microscope than with saline smear method. CONCLUSION: The liquid-based fungal method has a high positive coincidence rate and accuracy in the detection of vaginal fungi, and it is convenient to operate and implement steps. Therefore, it may be applied in clinical practice. Or a combination of several detection methods can be used.


Asunto(s)
Excreción Vaginal , Vaginitis , Femenino , Humanos , Vagina , Vaginitis/diagnóstico , Vaginitis/microbiología , Coloración y Etiquetado , Hongos
16.
Front Public Health ; 10: 958870, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36408050

RESUMEN

Emotion in the learning process can directly influence the learner's attention, memory, and cognitive activities. Several literatures indicate that hand-drawn painting could reflect the learner's emotional status. But, such an evaluation of emotional status, manually conducted by the psychologist, is usually subjective and inefficient for clinical practice. To address the issues of subjectivity and inefficiency in the painting based emotional analysis, we conducted an exploration of a painting based emotional analysis in learning environment by using convolutional neural network model. A painting image of 100 × 100 pixels was used as input for the model. The instant emotional statue of the learner was collected by filling out a questionnaire and was reviewed by a psychologist and then used as the label for training the convolutional neural network model. With the completion of convolutional, full-connected, and classification operations, the features of the painting image were learned from the underlying pixel matrix to the high-level semantic feature mapping. Then the emotional classification of the painting image could be made to reflect the learner's emotional status. Finally, the classification result by the model was compared with the result manually conducted by a psychologist to validate the model accuracy. We conducted an experiment in a university at Hangzhou, and 2,103 learners joined in the experiment. The learner was required to first fill out a questionnaire reporting emotional status in the learning process, and then to complete a theme-specified painting. Two thousand valid paintings were received and divided into training dataset (1,600) and test dataset (400). The experimental result indicated that the model achieved the accuracy of 72.1%, which confirmed the effectiveness of the model for emotional analysis.


Asunto(s)
Emociones , Redes Neurales de la Computación , Humanos , Aprendizaje
17.
J Immunol ; 209(10): 1987-1998, 2022 11 15.
Artículo en Inglés | MEDLINE | ID: mdl-36426955

RESUMEN

Pyroptosis is a form of regulated cell death mediated by the gasdermin protein family. During virus infection, cell pyroptosis restricts viral replication. The mechanisms of the tripartite motif (TRIM) protein family and IFN-stimulated genes (ISGs) against viruses have been studied. The role of TRIMs and ISGs in pyroptosis remains unclear. In this study, we show that TRIM21 interacts with ISG12a in viral infection and facilitates its translocation into the mitochondria by promoting its ubiquitination, thereby causing caspase 3 activation. Gasdermin E (GSDME) is specifically cleaved by caspase 3 upon viral infection, releasing the GSDME N-terminal domain, perforating the cell membrane, and causing cell pyroptosis. Our study uncovers a new mechanism of TRIM21 and ISG12a in regulating virus-induced cell pyroptosis.


Asunto(s)
Piroptosis , Virus , Piroptosis/fisiología , Caspasa 3/metabolismo , Ubiquitinación , Muerte Celular , Proteínas de Motivos Tripartitos/metabolismo
18.
Proc Natl Acad Sci U S A ; 119(49): e2210404119, 2022 12 06.
Artículo en Inglés | MEDLINE | ID: mdl-36442095

RESUMEN

Diapause is a form of dormancy used widely by insects to survive adverse seasons. Previous studies have demonstrated that forkhead box O (FoxO) is activated during pupal diapause initiation in the moth Helicoverpa armigera. However, it is unclear how FoxO induces diapause. Here, we show that knockout of FoxO causes H. armigera diapause-destined pupae to channel into nondiapause, indicating that FoxO is a master regulator that induces insect diapause. FoxO activates the ubiquitin-proteasome system (UPS) by promoting ubiquitin c (Ubc) expression via directly binding to the Ubc promoter. Activated UPS decreases transforming growth factor beta (TGFß) receptor signaling via ubiquitination to block developmental signaling to induce diapause. This study significantly advances the understanding of insect diapause by uncovering the detailed molecular mechanism of FoxO.


Asunto(s)
Diapausa de Insecto , Diapausa , Animales , Factor de Crecimiento Transformador beta , Pupa , Transducción de Señal , Receptores de Factores de Crecimiento Transformadores beta , Ubiquitina , Complejo de la Endopetidasa Proteasomal
19.
Adv Healthc Mater ; 11(21): e2200782, 2022 11.
Artículo en Inglés | MEDLINE | ID: mdl-36101484

RESUMEN

Impaired diabetic wound healing is associated with the persistence of chronic inflammation and excessive oxidative stress, which has become one of the most serious clinical challenges. Wound dressings with anti-inflammatory and reactive oxygen species (ROS)-scavenging properties are desirable for diabetic wound treatment. In this study, a shape-adaptable, biodegradable, biocompatible, antioxidant, and immunomodulatory interleukin-33 (IL-33)-cytogel is developed by encapsulating IL-33 into physically cross-linked DNA hydrogels and used as wound dressings to promote diabetic wound healing. The porous microstructures and biodegradable properties of the IL-33-cytogel ensure the local sustained-release of IL-33 in the wound area, where the sustained-release of IL-33 is maintained for at least 7 days. IL-33-cytogel can induce local accumulation of group 2 innate lymphoid cells (ILC2s) and regulatory T cells (Tregs), as well as M1-to-M2 transition at the wound sites. Additionally, the antioxidant and biocompatible characteristics of DNA hydrogels promote the scavenging of intracellular ROS without affecting cell viability. As a result, local inflammation in the diabetic wound area is resolved upon IL-33-cytogel treatment, which is accompanied by improved granulation tissue regeneration and accelerated wound closure. This study demonstrates a promising strategy in tissue engineering and regenerative medicine by incorporating DNA hydrogels and cytokine immunotherapy for promoting diabetic wound healing.


Asunto(s)
Diabetes Mellitus , Hidrogeles , Humanos , Hidrogeles/química , Antioxidantes , Interleucina-33 , Inmunidad Innata , Preparaciones de Acción Retardada , Especies Reactivas de Oxígeno , Citocinas , Linfocitos , Cicatrización de Heridas , Inflamación , ADN
20.
J Cell Mol Med ; 26(18): 4847-4858, 2022 09.
Artículo en Inglés | MEDLINE | ID: mdl-35975481

RESUMEN

Significant pancreatic islet dysfunction and loss shortly after transplantation to the liver limit the widespread implementation of this procedure in the clinic. Nonimmune factors such as reactive oxygen species and inflammation have been considered as the primary driving force for graft failure. The adipokine adiponectin plays potent roles against inflammation and oxidative stress. Previous studies have demonstrated that systemic administration of adiponectin significantly prevented islet loss and enhanced islet function at post-transplantation period. In vitro studies indicate that adiponectin protects islets from hypoxia/reoxygenation injury, oxidative stress as well as TNF-α-induced injury. By applying adenovirus mediated transfection, we now engineered islet cells to express exogenous adiponectin gene prior to islet transplantation. Adenovirus-mediated adiponectin transfer to a syngeneic suboptimal islet graft transplanted under kidney capsule markedly prevented inflammation, preserved islet graft mass and improved islet transplant outcomes. These results suggest that adenovirus-mediated adiponectin gene therapy would be a beneficial clinical engineering approach for islet preservation in islet transplantation.


Asunto(s)
Trasplante de Islotes Pancreáticos , Islotes Pancreáticos , Adenoviridae/genética , Adiponectina/genética , Terapia Genética , Supervivencia de Injerto , Humanos , Inflamación , Trasplante de Islotes Pancreáticos/métodos
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