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1.
Nat Immunol ; 24(12): 2032-2041, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37945822

RESUMEN

Cancer cells often overexpress CD47, which triggers the inhibitory receptor SIRPα expressed on macrophages, to elude phagocytosis and antitumor immunity. Pharmacological blockade of CD47 or SIRPα is showing promise as anticancer therapy, although CD47 blockade has been associated with hematological toxicities that may reflect its broad expression pattern on normal cells. Here we found that, in addition to triggering SIRPα, CD47 suppressed phagocytosis by a SIRPα-independent mechanism. This mechanism prevented phagocytosis initiated by the pro-phagocytic ligand, SLAMF7, on tumor cells, due to a cis interaction between CD47 and SLAMF7. The CD47-SLAMF7 interaction was disrupted by CD47 blockade and by a first-in-class agonist SLAMF7 antibody, but not by SIRPα blockade, thereby promoting antitumor immunity. Hence, CD47 suppresses phagocytosis not only by engaging SIRPα, but also by masking cell-intrinsic pro-phagocytic ligands on tumor cells and knowledge of this mechanism may influence the decision between CD47 blockade or SIRPα blockade for therapeutic purposes.


Asunto(s)
Antígeno CD47 , Neoplasias , Escape del Tumor , Humanos , Antígenos de Diferenciación/metabolismo , Antígenos de Diferenciación/uso terapéutico , Ligandos , Macrófagos , Neoplasias/tratamiento farmacológico , Neoplasias/inmunología , Neoplasias/patología , Fagocitosis , Animales , Ratones
2.
Nat Immunol ; 20(4): 447-457, 2019 04.
Artículo en Inglés | MEDLINE | ID: mdl-30833791

RESUMEN

Invariant natural killer T cells (iNKT cells) develop through an incompletely understood process that requires positive selection by CD4+CD8+ double-positive thymocytes and SLAM family receptors (SFRs). Here we found that SFRs promoted the development of iNKT cells by reducing the strength of the T cell antigen receptor (TCR) signal after positive selection. This effect improved the survival of iNKT cells and their responses to antigen. Loss of SFRs upregulated the expression of inhibitory receptors, including PD-1, on iNKT cells to mitigate the deleterious effect of SFR deficiency. The role of SFRs could be mimicked by expression of SLAMF6 alone in SFR-deficient mice, and this involved the adaptor SAP-kinase Fyn complex and the phosphatase SHP-1. Thus, SFRs foster iNKT cell development by attenuating TCR signal strength after positive selection.


Asunto(s)
Células T Asesinas Naturales/inmunología , Receptores de Antígenos de Linfocitos T/metabolismo , Familia de Moléculas Señalizadoras de la Activación Linfocitaria/fisiología , Animales , Proliferación Celular , Supervivencia Celular , Receptores Coestimuladores e Inhibidores de Linfocitos T/metabolismo , Humanos , Ratones , Ratones Noqueados , Células T Asesinas Naturales/enzimología , Proteína Tirosina Fosfatasa no Receptora Tipo 6/genética , Proteína Tirosina Fosfatasa no Receptora Tipo 6/metabolismo , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Proteínas Proto-Oncogénicas c-fyn/metabolismo , Receptores de Antígenos de Linfocitos T/inmunología , Transducción de Señal , Proteína Asociada a la Molécula de Señalización de la Activación Linfocitaria/genética , Familia de Moléculas Señalizadoras de la Activación Linfocitaria/genética , Familia de Moléculas Señalizadoras de la Activación Linfocitaria/metabolismo
3.
Immunology ; 2024 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-38618976

RESUMEN

Despite progress in cancer immunotherapy, ovarian cancer (OC) prognosis continues to be disappointing. Recent studies have shed light on how not just tumour cells, but also the complex tumour microenvironment, contribute to this unfavourable outcome of OC immunotherapy. The complexities of the immune microenvironment categorize OC as a 'cold tumour'. Nonetheless, understanding the precise mechanisms through which the microenvironment influences the effectiveness of OC immunotherapy remains an ongoing scientific endeavour. This review primarily aims to dissect the inherent characteristics and behaviours of diverse cells within the immune microenvironment, along with an exploration into its reprogramming and metabolic changes. It is expected that these insights will elucidate the operational dynamics of the immune microenvironment in OC and lay a theoretical groundwork for improving the efficacy of immunotherapy in OC management.

4.
J Am Chem Soc ; 146(7): 4795-4802, 2024 Feb 21.
Artículo en Inglés | MEDLINE | ID: mdl-38329998

RESUMEN

An iron/chromium system (Fe(OAc)2, CpCr(CO)3H) catalyzes the preparation of ß,γ- or γ,δ-unsaturated amides from 1,4,2-dioxazol-5-ones. An acyl nitrenoid iron complex seems likely to be responsible for C-H activation. A cascade of three H• transfer steps appears to be involved: (i) the abstraction of H• from a remote C-H bond by the nitrenoid N, (ii) the transfer of H• from Cr to N, and (iii) the abstraction of H• from a radical substituent by the Cr•. The observed kinetic isotope effects are consistent with the proposed mechanism if nitrenoid formation is the rate-determining step. The Fe/Cr catalysts can also desaturate substituted 1,4,2-dioxazol-5-ones to 3,5-dienamides.

5.
Small ; 20(7): e2306803, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37803480

RESUMEN

Lead-free dielectric capacitors have attracted significant research interest for high-power applications due to their environmental benefits and ability to meet the demanding performance requirements of electronic devices. However, the development of lead-free ceramic dielectrics with outstanding energy storage performance remains a challenge. In this study, environmentally friendly ceramic dielectrics with sandwich structures are designed and fabricated to improve energy storage performance via the synergistic effect of different dielectrics. The chemical compositions of the outer and middle layers of the sandwich structure are 0.35BiFeO3 -0.65SrTiO3 and Bi0.39 Na0.36 Sr0.25 TiO3 , respectively. The experimental and theoretical simulation results demonstrate that the breakdown strength is over 700 kV cm-1 for prepare sandwich structure ceramics. As a result, an ultrahigh recoverable energy storage density of 9.05 J cm-3 and a near-ideal energy storage efficiency of 97% are simultaneously achieved under 710 kV cm-1 . Furthermore, the energy storage efficiency maintains high values (≥ 96%) within 1-100 Hz and the power density as high as 188 MW cm-3 under 400 kV cm-1 . These results indicate that the designed lead-free ceramics with a sandwich structure possess superior comprehensive energy storage performance, making them promising lead-free candidates in the energy storage field.

6.
Fish Shellfish Immunol ; 145: 109364, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38199264

RESUMEN

Micropterus salmoides rhabdovirus (MSRV) is one of the main pathogens of largemouth bass, leading to serious economic losses. The G protein, as the only envelope protein present on the surface of MSRV virion, contains immune-related antigenic determinants, thereby becoming the primary target for the design of MSRV vaccines. Here, we displayed the G protein on the surface of yeast cells (named EBY100/pYD1-G) and conducted a preliminary assessment of the protective efficacy of the recombinant yeast vaccine. Upon oral vaccination, a robust immune response was observed in systemic and mucosal tissue. Remarkably, following the MSRV challenge, the relative percent survival of EBY100/pYD1-G treated largemouth bass significantly increased to 66.7 %. In addition, oral administration inhibited viral replication and alleviated the pathological symptoms of MSRV-infected largemouth bass. These results suggest that EBY100/pYD1-G could be used as a potential oral vaccine against MSRV infection.


Asunto(s)
Lubina , Enfermedades de los Peces , Rhabdoviridae , Animales , Saccharomyces cerevisiae , Vacunación , Proteínas Fúngicas , Vacunas Sintéticas
7.
Acta Pharmacol Sin ; 45(3): 531-544, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37919475

RESUMEN

Cardiac inflammation contributes to heart failure (HF) induced by isoproterenol (ISO) through activating ß-adrenergic receptors (ß-AR). Recent evidence shows that myeloid differentiation factor 2 (MD2), a key protein in endotoxin-induced inflammation, mediates inflammatory heart diseases. In this study, we investigated the role of MD2 in ISO-ß-AR-induced heart injuries and HF. Mice were infused with ISO (30 mg·kg-1·d-1) via osmotic mini-pumps for 2 weeks. We showed that MD2 in cardiomyocytes and cardiac macrophages was significantly increased and activated in the heart tissues of ISO-challenged mice. Either MD2 knockout or administration of MD2 inhibitor L6H21 (10 mg/kg every 2 days, i.g.) could prevent mouse hearts from ISO-induced inflammation, remodelling and dysfunction. Bone marrow transplantation study revealed that both cardiomyocyte MD2 and bone marrow-derived macrophage MD2 contributed to ISO-induced cardiac inflammation and injuries. In ISO-treated H9c2 cardiomyocyte-like cells, neonatal rat primary cardiomyocytes and primary mouse peritoneal macrophages, MD2 knockout or pre-treatment with L6H21 (10 µM) alleviated ISO-induced inflammatory responses, and the conditioned medium from ISO-challenged macrophages promoted the hypertrophy and fibrosis in cardiomyocytes and fibroblasts. We demonstrated that ISO induced MD2 activation in cardiomyocytes via ß1-AR-cAMP-PKA-ROS signalling axis, and induced inflammatory responses in macrophages via ß2-AR-cAMP-PKA-ROS axis. This study identifies MD2 as a key inflammatory mediator and a promising therapeutic target for ISO-induced heart failure.


Asunto(s)
Insuficiencia Cardíaca , Miocitos Cardíacos , Ratas , Ratones , Animales , Miocitos Cardíacos/metabolismo , Isoproterenol/toxicidad , Receptores Adrenérgicos beta/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Insuficiencia Cardíaca/inducido químicamente , Insuficiencia Cardíaca/metabolismo , Inflamación/inducido químicamente , Inflamación/metabolismo , Macrófagos/metabolismo
8.
Inhal Toxicol ; 36(1): 1-12, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38175690

RESUMEN

Background: Paraquat (PQ) plays an important role in agricultural production due to its highly effective herbicidal effect. However, it has led to multiple organ failure in those who have been poisoned, with damage most notable in the lungs and ultimately leading to death. Because of little research has been performed at the genetic level, and therefore, the specific genetic changes caused by PQ exposure are unclear.Methods: Paraquat poisoning model was constructed in Sprague Dawley (SD) rats, and SD rats were randomly divided into Control group, paraquat (PQ) poisoning group and Anthrahydroquinone-2,6-disulfonate (AH2QDS) treatment group. Then, the data was screened and quality controlled, compared with reference genes, optimized gene structure, enriched at the gene expression level, and finally, signal pathways with significantly different gene enrichment were screened.Results: This review reports on lung tissues from paraquat-intoxicated Sprague Dawley (SD) rats that were subjected to RNA-seq, the differentially expressed genes were mainly enriched in PI3K-AKT, cGMP-PKG, MAPK, Focal adhesion and other signaling pathways.Conclusion: The signaling pathways enriched with these differentially expressed genes are summarized, and the important mechanisms mediated through these pathways in acute lung injury during paraquat poisoning are outlined to identify important targets for AH2QDS treatment of acute lung injury due to paraquat exposure, information that will be used to support a subsequent in-depth study on the mechanism of PQ action.


Asunto(s)
Lesión Pulmonar Aguda , Paraquat , Ratas , Animales , Ratas Sprague-Dawley , Paraquat/toxicidad , RNA-Seq , Fosfatidilinositol 3-Quinasas/metabolismo , Fosfatidilinositol 3-Quinasas/farmacología , Lesión Pulmonar Aguda/inducido químicamente , Lesión Pulmonar Aguda/genética , Lesión Pulmonar Aguda/metabolismo , Pulmón , Transducción de Señal , Tecnología
9.
BMC Pediatr ; 24(1): 136, 2024 Feb 22.
Artículo en Inglés | MEDLINE | ID: mdl-38383331

RESUMEN

OBJECTIVE: To explore the effect of repetitive transcranial magnetic stimulation (rTMS)-assisted training on lower limb motor function in children with hemiplegic cerebral palsy (HCP). METHOD: Thirty-one children with HCP who met the inclusion criteria were selected and randomly divided into a control group (n = 16) and an experimental group (n = 15). The control group received routine rehabilitation treatment for 30 min each time, twice a day, 5 days a week for 4 weeks. Based on the control group, the experimental group received rTMS for 20 min each time, once a day, 5 days a week for 4 weeks. The outcome measures included a 10-metre walk test (10MWT), a 6-minute walk distance (6MWD) test, D- and E-zone gross motor function measurements (GMFM), the symmetry ratio of the step length and stance time and the muscle tone of the triceps surae and the hamstrings (evaluated according to the modified Ashworth scale), which were obtained in both groups of children before and after treatment. RESULTS: After training, the 10MWT (P < 0.05), 6MWD (P < 0.01), GMFM (P < 0.001) and the symmetry ratio of the step length and stance time of the two groups were significantly improved (P < 0.05), there was more of an improvement in the experimental group compared with the control group. There was no significant change in the muscle tone of the hamstrings between the two groups before and after treatment (P > 0.05). After treatment, the muscle tone of the triceps surae in the experimental group was significantly reduced (P < 0.05), but there was no significant change in the control group (P > 0.05). CONCLUSION: Repetitive TMS-assisted training can improve lower limb motor function in children with HCP.


Asunto(s)
Parálisis Cerebral , Estimulación Magnética Transcraneal , Niño , Humanos , Hemiplejía/etiología , Extremidad Inferior , Caminata
10.
J Craniofac Surg ; 35(4): e338-e341, 2024 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-38349342

RESUMEN

Extensive skin graft necrosis after auricle reconstruction surgery is a thorny problem for plastic surgeons. Four unilateral microtia patients were enrolled for extensive skin graft necrosis after ear elevation surgery. Early debridement and daily dressing changes were important for preoperative preparation. Surgical treatments involved local flaps and secondary split-thickness skin graft. After 3 to 12 months of follow-up, clear surface structures and obvious auricular sulcus were shown in all 4 patients. No cartilage exposure, skin necrosis, healing impairment, or other complications were found. We attribute the cause of extensive skin graft necrosis to subcutaneous hematoma. Local skin flaps and split-thickness skin grafting can be effective treatments for such situations. The use of temporoparietal fascial flap is unnecessary when poor graft survival is caused by subcutaneous hematoma.


Asunto(s)
Pabellón Auricular , Necrosis , Procedimientos de Cirugía Plástica , Trasplante de Piel , Colgajos Quirúrgicos , Humanos , Masculino , Trasplante de Piel/métodos , Procedimientos de Cirugía Plástica/métodos , Pabellón Auricular/cirugía , Niño , Femenino , Complicaciones Posoperatorias/cirugía , Desbridamiento , Microtia Congénita/cirugía , Terapia Recuperativa/métodos , Adolescente , Hematoma/cirugía , Hematoma/etiología
11.
Angew Chem Int Ed Engl ; : e202405878, 2024 May 07.
Artículo en Inglés | MEDLINE | ID: mdl-38713005

RESUMEN

Lattice mismatch significantly influences microscopic transport in semiconducting devices, affecting interfacial charge behavior and device efficacy. This atomic-level disordering, often overlooked in previous research, is crucial for device efficiency and lifetime. Recent studies have highlighted emerging challenges related to lattice mismatch in perovskite solar cells, especially at heterojunctions, revealing issues like severe tensile stress, increased ion migration, and reduced carrier mobility. This review systematically discusses the effects of lattice mismatch on strain, material stability, and carrier dynamics. It also includes detailed characterizations of these phenomena and summarizes current strategies including epitaxial growth and buffer layer, as well as explores future solutions to mitigate mismatch-induced issues. We also provide the challenges and prospects for lattice mismatch, aiming to enhance the efficiency and stability of perovskite solar cells, and contribute to renewable energy technology advancements.

12.
J Am Chem Soc ; 145(41): 22384-22393, 2023 Oct 18.
Artículo en Inglés | MEDLINE | ID: mdl-37774115

RESUMEN

In the course of our investigations of the adsorption of ions to the air-water interface, we previously reported the surprising result that doubly charged carbonate anions exhibit a stronger surface affinity than singly charged bicarbonate anions. In contrast to monovalent, weakly hydrated anions, which generally show enhanced concentrations in the interfacial region, multivalent (and strongly hydrated) anions are expected to show a much weaker surface propensity. In the present work, we use resonantly enhanced deep-UV second-harmonic generation spectroscopy to measure the Gibbs free energy of adsorption of both carbonate (CO32-) and bicarbonate (HCO3-) anions to the air-water interface. Contrasting the predictions of classical electrostatic theory and in support of our previous findings from X-ray photoelectron spectroscopy, we find that carbonate anions do indeed exhibit much stronger surface affinity than do the bicarbonate anions. Extensive computer simulations reveal that strong ion pairing of CO32- with the Na+ countercation in the interfacial region results in the formation of near-neutral agglomerate clusters, consistent with a theory of interfacial ion adsorption based on hydration free energy and capillary waves. Simulated X-ray photoelectron spectra predict a 1 eV shift in the carbonate spectra compared to that of bicarbonate, further confirming our experiments. These findings not only advance our fundamental understanding of ion adsorption chemistry but also impact important practical processes such as ocean acidification, sea-spray aerosol chemistry, and mammalian respiration physiology.

13.
Clin Immunol ; 248: 109250, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36738816

RESUMEN

BACKGROUNDS: HLA-B*58:01 allele was strongly associated with allopurinol induced severe cutaneous adverse drug reaction (SCAR). However, HLA-B genotype is not sufficient to predict the occurrence of allopurinol-induced SCAR. OBJECTIVE: To discover DNA methylation markers for allopurinol-induced SCAR which may improve the prediction accuracy of genetic testing. STUDY DESIGN: The study was designed as a retrospective case-control clinical study in multicenter hospitals across Taiwan, Mainland China, Malaysia and Canada. 125 cases of allopurinol-induced SCAR patients and 139 cases of allopurinol tolerant controls were enrolled in this study during 2005 to 2021. RESULTS: The results of genome-wide DNA methylation assay of 62 patients revealed that ITGB2 showed strong discriminative ability of allopurinol-induced SCAR in both HLA-B*58:01 positive and negative patients with AUC value of 0.9364 (95% CI 0.8682-1.000). In validation study, significant hypermethylation of ITGB2 were further validated in allopurinol-induced SCAR patients compared to tolerant controls, especially in those without HLA-B*58:01(AUC value of 0.8814 (95% CI 0.7121-1.000)). Additionally, the methylation levels of 2 sites on ITGB2 were associated with SCAR phenotypes. Combination of HLA-B*58:01 genotyping and ITGB2 methylation status could improve the prediction accuracy of allopurinol-induced SCAR with the AUC value up to 0.9387 (95% CI 0.9089-0.9684), while the AUC value of HLA-B*58:01 genotyping alone was 0.8557 (95% CI 0.8030-0.9083). CONCLUSIONS: Our study uncovers differentially methylated genes between allopurinol-induced SCAR patients and tolerant controls with positive or negative HLA-B*58:01 allele and provides the novel epigenetic marker that improves the prediction accuracy of genetic testing for prevention of allopurinol-induced SCAR.


Asunto(s)
Hipersensibilidad a las Drogas , Síndrome de Stevens-Johnson , Humanos , Alopurinol/efectos adversos , Estudios Retrospectivos , Metilación de ADN , Hipersensibilidad a las Drogas/epidemiología , Antígenos HLA-B/genética , Síndrome de Stevens-Johnson/tratamiento farmacológico , Síndrome de Stevens-Johnson/genética
14.
Small ; 19(6): e2206125, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36461726

RESUMEN

Owing to the high power density, eco-friendly, and outstanding stability, the lead-free ceramics have attracted great interest in the fields of pulsed power systems. Nevertheless, the low energy storage density of such ceramics is undoubtedly a severe problem in practical applications. To overcome this limitation, the lead-free ceramics with gradient structures are designed and fabricated using the tape-casting method herein. By optimizing the composition and distribution of the gradient-structured ceramics, the energy storage density, and efficiency can be improved simultaneously. Under a moderate electric field of 320 kV cm-1 , the value of recoverable energy storage density (Wrec ) is higher than 4 J cm-3 , and the energy storage efficiency (η) is of ≥88% for 20-5-20 and 20-10-20. Furthermore, the gradient-structured ceramics of 20-10-0-10-20 and 20-15-0-15-20 possess high applied electric field, large maximum polarization, and small remnant polarization, which give rise to ultrahigh Wrec and η on the order of ≈6.5 J cm-3 and 89-90%, respectively. In addition, the energy storage density and efficiency also exhibit excellent stability over a broad range of frequencies, temperatures, and cycling numbers. This work provides an effective strategy for improving the energy storage capability of eco-friendly ceramics.

15.
Small ; 19(37): e2302376, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37140075

RESUMEN

PbYb0.5 Nb0.5 O3 (PYN)-based ceramics, featured by their ultra-high phase-switching field and low sintering temperature (950 °C), are of great potential in exploiting dielectric ceramics with high energy storage density and low preparation cost. However, due to insufficient breakdown strength (BDS), their complete polarization-electric field (P-E) loops are difficult to be obtained. Here, to fully reveal their potential in energy storage, synergistic optimization strategy of composition design with Ba2+ substitution and microstructure engineering via hot-pressing (HP) are adopted in this work. With 2 mol% Ba2+ doping, a recoverable energy storage density (Wrec ) of 10.10 J cm-3 and a discharge energy density (Wdis ) of 8.51 J cm-3 can be obtained, supporting the superior current density (CD ) of 1391.97 A cm-2 and the outstanding power density (PD ) of 417.59 MW cm-2 . In situ characterization methods are utilized here to reveal the unique movement of the B-site ions of PYN-based ceramics under electric field, which is the key factor of the ultra-high phase-switching field. It is also confirmed that microstructure engineering can refine the grain of ceramics and improve BDS. This work strongly demonstrates the potential of PYN-based ceramics in energy storage field and plays a guiding role in the follow-up research.

16.
J Transl Med ; 21(1): 452, 2023 07 08.
Artículo en Inglés | MEDLINE | ID: mdl-37422640

RESUMEN

BACKGROUND: Osteoarthritis (OA), in which macrophage-driven synovitis is considered closely related to cartilage destruction and could occur at any stage, is an inflammatory arthritis. However, there are no effective targets to cure the progression of OA. The NOD-, LRR-,and pyrin domain-containing protein 3 (NLRP3) inflammasome in synovial macrophages participates in the pathological inflammatory process and treatment strategies targeting it are considered to be an effective approach for OA. PIM-1 kinase, as a downstream effector of many cytokine signaling pathways, plays a pro-inflammatory role in inflammatory disease. METHODS: In this study, we evaluated the expression of the PIM-1 and the infiltration of synovial macrophages in the human OA synovium. The effects and mechanism of PIM-1 were investigated in mice and human macrophages stimulated by lipopolysaccharide (LPS) and different agonists such as nigericin, ATP, Monosodium urate (MSU), and Aluminum salt (Alum). The protective effects on chondrocytes were assessed by a modified co-culture system induced by macrophage condition medium (CM). The therapeutic effect in vivo was confirmed by the medial meniscus (DMM)-induced OA in mice. RESULTS: The expression of PIM-1 was increased in the human OA synovium which was accompanied by the infiltration of synovial macrophages. In vitro experiments, suppression of PIM-1 by SMI-4a, a specific inhibitor, rapidly inhibited the NLRP3 inflammasome activation in mice and human macrophages and gasdermin-D (GSDME)-mediated pyroptosis. Furthermore, PIM-1 inhibition specifically blocked the apoptosis-associated speck-like protein containing a CARD (ASC) oligomerization in the assembly stage. Mechanistically, PIM-1 inhibition alleviated the mitochondrial reactive oxygen species (ROS)/chloride intracellular channel proteins (CLICs)-dependent Cl- efflux signaling pathway, which eventually resulted in the blockade of the ASC oligomerization and NLRP3 inflammasome activation. Furthermore, PIM-1 suppression showed chondroprotective effects in the modified co-culture system. Finally, SMI-4a significantly suppressed the expression of PIM-1 in the synovium and reduced the synovitis scores and the Osteoarthritis Research Society International (OARSI) score in the DMM-induced OA model. CONCLUSIONS: Therefore, PIM-1 represented a new class of promising targets as a treatment of OA to target these mechanisms in macrophages and widened the road to therapeutic strategies for OA.


Asunto(s)
Osteoartritis , Sinovitis , Humanos , Ratones , Animales , Inflamasomas/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Osteoartritis/tratamiento farmacológico , Macrófagos/metabolismo , Transducción de Señal , Sinovitis/metabolismo , Interleucina-1beta/metabolismo , Canales de Cloruro/metabolismo , Canales de Cloruro/farmacología , Canales de Cloruro/uso terapéutico , Proteínas Mitocondriales/metabolismo
17.
Inorg Chem ; 62(38): 15641-15650, 2023 Sep 25.
Artículo en Inglés | MEDLINE | ID: mdl-37690055

RESUMEN

When it comes to an efficient catalytic oxygen evolution reaction (OER) in the production of renewable energy and chemicals, the construction of heterogeneous structures is crucial to break the linear scalar relationship of a single catalyst. This heterogeneous structure construction helps creatively achieve high activity and stability. However, the synthesis process of heterogeneous crystalline materials is often complex and challenging to capture and reproduce, which limits their application. Here, the dynamic process of structural changes in Co-MOFs in alkali was captured by in situ powder X-ray diffraction, FT-IR spectroscopy, and Raman spectroscopy, and several self-reconfigured MOF heterogeneous materials with different structures were stably isolated. The created ß-Co(OH)2/Co-MOF heterojunction structure facilitates rapid mass-charge transfer and exposure of active sites, which significantly enhanced OER activity. Experimental results show that this heterogeneous structure achieves a low overpotential of 333 mV at 10 mA cm-2. The findings provide new insights and directions for the search for highly reactive cobalt-based MOFs for sustainable energy technologies.

18.
Exp Cell Res ; 417(1): 113210, 2022 08 01.
Artículo en Inglés | MEDLINE | ID: mdl-35597298

RESUMEN

Cancer cells acquire immunoediting ability to evade immune surveillance and thus escape eradication. It is widely known that mutant proteins encoded from tumor suppressor TP53 exhibit gain-of-function in cancer cells, thereby promoting progression; however, how mutant p53 contributes to the sheltering of cancer cells from host anticancer immunity remains unclear. Herein, we report that murine p53 missense mutation G242A (corresponding to human G245A) suppresses the activation of host natural killer (NK) cells, thereby enabling breast cancer cells to avoid immune assault. We found that serial injection of EMT6 breast cancer cells that carry wild-type (wt) Trp53, like normal fibroblasts, promoted NK activity in mice, while SVTneg2 cells carrying Trp53 G242A+/+ mutation decreased NK cell numbers and increased CD8+ T lymphocyte numbers in spleen. Innate immunity based on NK cells and CD8 T cells was reduced in p53 mutant-carrying transgenic mice (Trp53 R172H/+, corresponding to human R175H/+). Further, upon co-culture with isolated NK cells, EMT6 cells substantively activated NK cells and proliferation thereof, increasing interferon-gamma (IFN-γ) production; however, SVTneg2 cells suppressed NK cell activation. Further mechanistic study elucidated that p53 can modulate expression by cancer cells of Mult-1 and H60a, which are activating and inhibitory ligands for NKG2D receptors of NK cells, respectively, to enhance immune surveillance against cancer. Our findings demonstrate that wt p53 is requisite for NK cell-based immune recognition and elimination of cancerous cells, and perhaps more importantly, that p53 missense mutant presence in cancer cells impairs NK cell-attributable responses, thus veiling cancerous cells from host immunity and enabling cancer progression.


Asunto(s)
Neoplasias de la Mama , Células Asesinas Naturales , Proteína p53 Supresora de Tumor , Animales , Neoplasias de la Mama/genética , Neoplasias de la Mama/inmunología , Femenino , Células Asesinas Naturales/metabolismo , Ratones , Ratones Transgénicos , Subfamilia K de Receptores Similares a Lectina de Células NK/genética , Subfamilia K de Receptores Similares a Lectina de Células NK/metabolismo , Proteína p53 Supresora de Tumor/genética , Proteína p53 Supresora de Tumor/metabolismo
19.
Nucleic Acids Res ; 49(1): 15-24, 2021 01 11.
Artículo en Inglés | MEDLINE | ID: mdl-33330935

RESUMEN

RNA polymerase pausing during elongation is an important mechanism in the regulation of gene expression. Pausing along DNA templates is thought to be induced by distinct signals encoded in the nucleic acid sequence and halt elongation complexes to allow time for necessary co-transcriptional events. Pausing signals have been classified as those producing short-lived elemental, long-lived backtracked, or hairpin-stabilized pauses. In recent years, structural microbiology and single-molecule studies have significantly advanced our understanding of the paused states, but the dynamics of these states are still uncertain, although several models have been proposed to explain the experimentally observed pausing behaviors. This review summarizes present knowledge about the paused states, discusses key discrepancies among the kinetic models and their basic assumptions, and highlights the importance and challenges in constructing theoretical models that may further our biochemical understanding of transcriptional pausing.


Asunto(s)
Proteínas Bacterianas/metabolismo , ADN Bacteriano/genética , ARN Polimerasas Dirigidas por ADN/metabolismo , Modelos Genéticos , ARN Bacteriano/biosíntesis , Elongación de la Transcripción Genética , Dominio Catalítico , Cristalografía por Rayos X , Proteínas de Escherichia coli/metabolismo , Cinética , Modelos Moleculares , Conformación de Ácido Nucleico , Conformación Proteica , ARN Bacteriano/genética , Thermus thermophilus/genética , Factores de Tiempo
20.
Int J Neurosci ; 133(4): 450-456, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33975502

RESUMEN

PURPOSE/AIM: Cerebellopontine angle (CPA) oligodendrogliomas are very rare, and only three preoperative cases have been confirmed. Secondary CPA oligodendrogliomas after radiation therapy are exceptionally rare, and no other cases have been reported. CASE REPORT: We present a case of a 25-year-old male with CPA oligodendroglioma who experienced hearing loss in right ear with walking instability for more than 2 months. The patient underwent craniotomy in our hospital because of grade II astrocytoma of the right temporal lobe 10 years ago. Postoperative radiotherapy lasted for 30 days, and six rounds of chemotherapy were performed. Magnetic resonance imaging (MRI) of the head revealed a cystic lesion located in the right CPA. The patient underwent surgery without obvious complications, and the tumor was subtotally removed. Histopathological examination revealed a diagnosis of oligodendroglioma, World Health Organization (WHO) grade II. The patient was discharged on the tenth postoperative day with a good recovery. Two weeks after discharge, chemotherapy with temozolomide and radiotherapy were performed. The patient remained well at 8 months follow-up. CONCLUSIONS: To the best of our knowledge, no other cases of secondary CPA oligodendroglioma after cranial irradiation have been reported in the literature. Compared with general oligodendroglioma, the tumor has no typical calcification and is more aggressive. The cranial nerves in the CPA area are closely adhered, and the blood supply is abnormally rich. It is difficult to completely remove the tumor. Postoperative radiotherapy and chemotherapy should be carried out as soon as possible.


Asunto(s)
Astrocitoma , Oligodendroglioma , Masculino , Humanos , Adulto , Oligodendroglioma/diagnóstico por imagen , Oligodendroglioma/etiología , Oligodendroglioma/cirugía , Ángulo Pontocerebeloso/diagnóstico por imagen , Ángulo Pontocerebeloso/patología , Ángulo Pontocerebeloso/cirugía , Astrocitoma/diagnóstico , Irradiación Craneana , Temozolomida , Imagen por Resonancia Magnética
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