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3.
ISA Trans ; 147: 567-576, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38378403

RESUMEN

Variable stiffness actuators (VSAs) are essential for ensuring safe human-robot interactions in robotic applications. This paper proposes a novel rotary VSA using an antagonistic Hoberman linkage mechanism (AHLM), which offers a large stiffness range and a compact structure. The VSA-AHLM consists of two sets of antagonistic-type quadratic springs based on spiral cams connected to the Hoberman linkage mechanism (HLM) through four cables. By simultaneously adjusting both the radius of the HLM and the spring preload, the stiffness of the VSA-AHLM can be varied within a large range. Furthermore, the position and stiffness of the VSA-AHLM can be controlled independently by two rotary motors. The geometric parameters of the spiral cam are determined to achieve the desired linear stiffness-elongation behavior of a quadratic spring, and detailed models of the actuator's stiffness, elastic energy, and torque are established. An actuator prototype is fabricated to demonstrate the proposed variable stiffness approach. Experiments show that the developed actuator can achieve significant stiffness changes and exhibits excellent positioning and trajectory tracking performance.

4.
Mol Carcinog ; 63(4): 647-662, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38197491

RESUMEN

Colorectal cancer (CRC) continues to be a prevalent malignancy, posing a significant risk to human health. The involvement of alpha/beta hydrolase domain 6 (ABHD6), a serine hydrolase family member, in CRC development was suggested by our analysis of clinical data. However, the role of ABHD6 in CRC remains unclear. This study seeks to elucidate the clinical relevance, biological function, and potential molecular mechanisms of ABHD6 in CRC. We investigated the role of ABHD6 in clinical settings, conducting proliferation, migration, and cell cycle assays. To determine the influence of ABHD6 expression levels on Oxaliplatin sensitivity, we also performed apoptosis assays. RNA sequencing and KEGG analysis were utilized to uncover the potential molecular mechanisms of ABHD6. Furthermore, we validated its expression levels using Western blot and reactive oxygen species (ROS) detection assays. Our results demonstrated that ABHD6 expression in CRC tissues was notably lower compared to adjacent normal tissues. This low expression correlated with a poorer prognosis for CRC patients. Moreover, ABHD6 overexpression impeded CRC cell proliferation and migration while inducing G0/G1 cell cycle arrest. In vivo experiments revealed that downregulation of ABHD6 resulted in an increase in tumor weight and volume. Mechanistically, ABHD6 overexpression inhibited the activation of the AKT signaling pathway and decreased ROS levels in CRC cells, suggesting the role of ABHD6 in CRC progression via the AKT signaling pathway. Our findings demonstrate that ABHD6 functions as a tumor suppressor, primarily by inhibiting the AKT signaling pathway. This role establishes ABHD6 as a promising prognostic biomarker and a potential therapeutic target for CRC patients.


Asunto(s)
Neoplasias Colorrectales , Proteínas Proto-Oncogénicas c-akt , Humanos , Especies Reactivas de Oxígeno , Proliferación Celular , Puntos de Control de la Fase G1 del Ciclo Celular , Hidrolasas , Transducción de Señal , Neoplasias Colorrectales/genética , Línea Celular Tumoral , Movimiento Celular , Monoacilglicerol Lipasas
5.
Rice (N Y) ; 17(1): 1, 2024 Jan 03.
Artículo en Inglés | MEDLINE | ID: mdl-38170415

RESUMEN

Reactive oxygen species (ROS) act as a group of signaling molecules in rice functioning in regulation of development and stress responses. Respiratory burst oxidase homologues (Rbohs) are key enzymes in generation of ROS. However, the role of the nine Rboh family members was not fully understood in rice multiple disease resistance and yield traits. In this study, we constructed mutants of each Rboh genes and detected their requirement in rice multiple disease resistance and yield traits. Our results revealed that mutations of five Rboh genes (RbohA, RbohB, RbohE, RbohH, and RbohI) lead to compromised rice blast disease resistance in a disease nursery and lab conditions; mutations of five Rbohs (RbohA, RbohB, RbohC, RbohE, and RbohH) result in suppressed rice sheath blight resistance in a disease nursery and lab conditions; mutations of six Rbohs (RbohA, RbohB, RbohC, RbohE, RbohH and RbohI) lead to decreased rice leaf blight resistance in a paddy yard and ROS production induced by PAMPs and pathogen. Moreover, all Rboh genes participate in the regulation of rice yield traits, for all rboh mutants display one or more compromised yield traits, such as panicle number, grain number per panicle, seed setting rate, and grain weight, resulting in reduced yield per plant except rbohb and rbohf. Our results identified the Rboh family members involved in the regulation of rice resistance against multiple pathogens that caused the most serious diseases worldwide and provide theoretical supporting for breeding application of these Rbohs to coordinate rice disease resistance and yield traits.

6.
Biomed Pharmacother ; 170: 115975, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38070246

RESUMEN

Osteoarthritis (OA) is characterized by gradual articular cartilage degradation, accompanied by persistent low-grade joint inflammation, correlating with radiographic and pain-related progression. The latent therapeutic potential of DZ2002, a reversible inhibitor of S-adenosyl-L-homocysteine hydrolase (SAHH), holds promise for OA intervention. This study endeavored to examine the therapeutic efficacy of DZ2002 within the milieu of OA. The cytotoxicity of DZ2002 was evaluated using the MTT assay on bone marrow-derived macrophages. The inhibitory impact of DZ2002 during the process of osteoclastogenesis was assessed using TRAP staining, analysis of bone resorption pits, and F-actin ring formation. Mechanistic insights were derived from qPCR and Western blot analyses. Through the intra-articular injection of monosodium iodoacetate (MIA), an experimental rat model of OA was successfully instituted. This was subsequently accompanied by a series of assessments including Von Frey filament testing, analysis of weight-bearing behaviors, and micro-CT imaging, all aimed at assessing the effectiveness of DZ2002. The findings emphasized the effectiveness of DZ2002 in mitigating osteoclastogenesis induced by M-CSF/RANKL, evident through a reduction in TRAP-positive OCs and bone resorption. Moreover, DZ2002 modulated bone resorption-associated gene and protein expression (CTSK, CTR, Integrin ß3) via the MEK/ERK pathway. Encouragingly, DZ2002 also alleviates MIA-induced pain, cartilage degradation, and bone loss. In conclusion, DZ2002 emerges as a potential therapeutic contender for OA, as evidenced by its capacity to hinder in vitro M-CSF/RANKL-induced osteoclastogenesis and mitigate in vivo osteoarthritis progression. This newfound perspective provides substantial support for considering DZ2002 as a compelling agent for osteoarthritis intervention.


Asunto(s)
Resorción Ósea , Cartílago Articular , Osteoartritis , Ratas , Animales , Ácido Yodoacético/efectos adversos , Ácido Yodoacético/metabolismo , Factor Estimulante de Colonias de Macrófagos/metabolismo , Sistema de Señalización de MAP Quinasas , Osteoartritis/inducido químicamente , Osteoartritis/tratamiento farmacológico , Osteoartritis/metabolismo , Dolor/tratamiento farmacológico , Cartílago Articular/metabolismo , Resorción Ósea/metabolismo , Quinasas de Proteína Quinasa Activadas por Mitógenos/metabolismo , Modelos Animales de Enfermedad
7.
Acta Pharmacol Sin ; 45(1): 166-179, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37605050

RESUMEN

Dry eye disease (DED) is a prevalent ocular disorder with a multifactorial etiology. The pre-angiogenic and pre-inflammatory milieu of the ocular surface plays a critical role in its pathogenesis. DZ2002 is a reversible type III S-adenosyl-L-homocysteine hydrolase (SAHH) inhibitor, which has shown excellent anti-inflammatory and immunosuppressive activities in vivo and in vitro. In this study, we evaluated the therapeutic potential of DZ2002 in rodent models of DED. SCOP-induced dry eye models were established in female rats and mice, while BAC-induced dry eye model was established in female rats. DZ2002 was administered as eye drops (0.25%, 1%) four times daily (20 µL per eye) for 7 or 14 consecutive days. We showed that topical application of DZ2002 concentration-dependently reduced corneal neovascularization and corneal opacity, as well as alleviated conjunctival irritation in both DED models. Furthermore, we observed that DZ2002 treatment decreased the expression of genes associated with angiogenesis and the levels of inflammation in the cornea and conjunctiva. Moreover, DZ2002 treatment in the BAC-induced DED model abolished the activation of the STAT3-PI3K-Akt-NF-κB pathways in corneal tissues. We also found that DZ2002 significantly inhibited the proliferation, migration, and tube formation of human umbilical endothelial cells (HUVECs) while downregulating the activation of the STAT3-PI3K-Akt-NF-κB pathway. These results suggest that DZ2002 exerts a therapeutic effect on corneal angiogenesis in DED, potentially by preventing the upregulation of the STAT3-PI3K-Akt-NF-κB pathways. Collectively, DZ2002 is a promising candidate for ophthalmic therapy, particularly in treating DED.


Asunto(s)
Neovascularización de la Córnea , Síndromes de Ojo Seco , Ratas , Humanos , Ratones , Animales , Femenino , Neovascularización de la Córnea/tratamiento farmacológico , Neovascularización de la Córnea/metabolismo , Neovascularización de la Córnea/patología , FN-kappa B/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Roedores/metabolismo , Células Endoteliales/metabolismo , Angiogénesis , Inflamación/tratamiento farmacológico , Síndromes de Ojo Seco/tratamiento farmacológico , Síndromes de Ojo Seco/inducido químicamente , Factor de Transcripción STAT3/metabolismo
8.
Plant Biotechnol J ; 22(1): 116-130, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37752622

RESUMEN

Arabidopsis RESISTANCE TO POWDERY MILDEW 8.1 (RPW8.1) is an important tool for engineering broad-spectrum disease resistance against multiple pathogens. Ectopic expression of RPW8.1 leads to enhanced disease resistance with cell death at leaves and compromised plant growth, implying a regulatory mechanism balancing RPW8.1-mediated resistance and growth. Here, we show that RPW8.1 constitutively enhances the expression of transcription factor WRKY51 and activates salicylic acid and ethylene signalling pathways; WRKY51 in turn suppresses RPW8.1 expression, forming a feedback regulation loop. RPW8.1 and WRKY51 are both induced by pathogen infection and pathogen-/microbe-associated molecular patterns. In ectopic expression of RPW8.1 background (R1Y4), overexpression of WRKY51 not only rescues the growth suppression and cell death caused by RPW8.1, but also suppresses RPW8.1-mediated broad-spectrum disease resistance and pattern-triggered immunity. Mechanistically, WRKY51 directly binds to and represses RPW8.1 promoter, thus limiting the expression amplitude of RPW8.1. Moreover, WRKY6, WRKY28 and WRKY41 play a role redundant to WRKY51 in the suppression of RPW8.1 expression and are constitutively upregulated in R1Y4 plants with WRKY51 being knocked out (wrky51 R1Y4) plants. Notably, WRKY51 has no significant effects on disease resistance or plant growth in wild type without RPW8.1, indicating a specific role in RPW8.1-mediated disease resistance. Altogether, our results reveal a regulatory circuit controlling the accumulation of RPW8.1 to an appropriate level to precisely balance growth and disease resistance during pathogen invasion.


Asunto(s)
Proteínas de Arabidopsis , Arabidopsis , Proteínas de Arabidopsis/metabolismo , Resistencia a la Enfermedad/genética , Retroalimentación , Arabidopsis/metabolismo , Muerte Celular , Enfermedades de las Plantas/genética , Regulación de la Expresión Génica de las Plantas/genética
9.
Chem Commun (Camb) ; 59(84): 12573-12576, 2023 Oct 19.
Artículo en Inglés | MEDLINE | ID: mdl-37812075

RESUMEN

Invisible inks have been applied for the secrecy of texts, symbols and binary images. Based on the photochromism of donor-acceptor Stenhouse adducts (DASAs) in the solid-state promoted by ester-containing molecules, we report the encryption of grayscale information by controlling the kinetics of photoisomerization.

10.
Nano Lett ; 23(21): 9900-9906, 2023 Nov 08.
Artículo en Inglés | MEDLINE | ID: mdl-37862605

RESUMEN

Scanning near-field optical microscope (SNOM) with nanoscale spatial resolution has been a powerful tool in studying the plasmonic properties of nano materials/structures. However, the quantification of the SNOM measurement remains a major challenge in the field due to the lack of reliable methodologies. We employed the point-dipole model to describe the tip-surface interaction upon laser illumination and theoretically derived the quantitative relationship between the measured results and the actual near-field electric field strength. Thus, we can experimentally reconstruct the near-field electric field through this theoretically calculated relationship. We also developed an experimental technique together with FEM simulation to get the above relationship experimentally and reconstruct the near-field electric field from the measurement by SNOM.

11.
Proc Inst Mech Eng H ; 237(9): 1039-1051, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37571990

RESUMEN

A novel passive hip exoskeleton has been designed and built with the aim of reducing metabolic consumption during walking by a passive way of storing the negative mechanical energy in the deceleration phase and releasing it in the acceleration phase. A ratchet spiral spring mechanism with a set of double stable switches is designed inside the exoskeleton for the above purpose. An analysis is conducted on the mechanism and the switching timing for the energy management to automatically store or release the energy according to the biomechanics of walking. In addition, a gravity-balance mechanism embedded inside the exoskeleton is designed as well to minimize the influence of the lower limb weight on muscle work. Human-exoskeleton interaction has been studied using the Opensim software, and simulation results demonstrated the effectiveness of the exoskeleton in reducing metabolic consumption during walking. An exoskeleton prototype has been built and tested with experiments measuring assistive torque and surface electromyography signal, confirming the effectiveness of the gravity-balance mechanism and energy-storage method, as well as the exoskeleton's actual assistive effect.


Asunto(s)
Dispositivo Exoesqueleto , Humanos , Caminata/fisiología , Articulación de la Cadera , Extremidad Inferior , Electromiografía/métodos , Fenómenos Biomecánicos/fisiología
12.
Natl Sci Rev ; 10(7): nwad136, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-37396487

RESUMEN

Non-linear materials are cornerstones of modern optics and electronics. Strong dependence on the intrinsic properties of particular materials, however, inhibits the at-will extension of demanding non-linear effects, especially those second-order ones, to widely adopted centrosymmetric materials (for example, silicon) and technologically important burgeoning spectral domains (for example, terahertz frequencies). Here we introduce a universal route to efficient non-linear responses enabled by exciting non-linear Thomson scattering, a fundamental process in electrodynamics that was known to occur only in relativistic electrons in metamaterial composed of linear materials. Such a mechanism modulates the trajectory of charges, either intrinsically or extrinsically provided in solids, at twice the driving frequency, allowing second-harmonic generation at terahertz frequencies on crystalline silicon with extremely large non-linear susceptibility in our proof-of-concept experiments. By offering a substantially material- and frequency-independent platform, our approach opens new possibilities in the fields of on-demand non-linear optics, terahertz sources, strong field light-solid interactions and integrated photonic circuits.

13.
Pathol Res Pract ; 245: 154426, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-37054577

RESUMEN

OBJECTIVE: To investigate the expression of chromosome 6 open reading frame 15 (C6orf15) in colon cancer and its effects on clinicopathological features and prognosis. METHODS: Using the transcriptome and clinical data of colon cancer and normal tissues in The Cancer Genome Atlas (TCGA) database, the expression of C6orf15 mRNA in colon cancer samples and its relationship with clinicopathological characteristics and prognosis were explored. The expression level of C6orf15 protein in 23 colon cancer tissues was detected by immunohistochemistry (IHC). The possible mechanism of C6orf15 involved in the occurrence and development of colon cancer was explored by gene set enrichment analysis (GSEA). RESULTS: Compared with normal tissues, C6orf15 was highly expressed in colon cancer (1.207 ± 0.694 vs 0.276 ± 0.166, t = 8.281, P < 0.01). The expression level of C6orf15 was associated with tumor invasion depth (χ2 = 8.30, P = 0.04), lymph node metastasis (χ2 = 36.97, P < 0.001), distant metastasis (χ2 = 8.69, P = 0.003) and pathological stage (χ2 = 34.17, P < 0.001). High expression of C6orf15 was associated with poor prognosis (χ2 = 6.43, P < 0.05). The results of GSEA showed that C6orf15 promotes the occurrence and development of colon cancer by promoting the ECM receptor interaction pathway, Hedgehog signaling pathway and Wnt signaling pathway. Immunohistochemical results showed that the expression of C6orf15 protein in colon cancer tissues was correlated with the depth of invasion (P = 0.023) and lymph node metastasis (P = 0.048). CONCLUSION: C6orf15 is highly expressed in colon cancer tissue and is related to adverse pathological features and poor prognosis of colon cancer. It is involved in multiple oncogenic signaling pathways and may serve as a prognostic marker of colon cancer.


Asunto(s)
Neoplasias del Colon , Proteínas Hedgehog , Humanos , Neoplasias del Colon/patología , Metástasis Linfática , Pronóstico
14.
Int J Colorectal Dis ; 38(1): 94, 2023 Apr 13.
Artículo en Inglés | MEDLINE | ID: mdl-37055602

RESUMEN

BACKGROUND: We performed this study to identify predictive factors for lymph node metastasis (LNM) and analyze the impact of LNM on the prognosis of patients with T1-2 colorectal cancer (CRC), with the intention of providing guidance for the treatment. METHODS: The Surveillance Epidemiology and End Result database was used to identify 20,492 patients diagnosed with T1-2 stage CRC between 2010 and 2019, who underwent surgery and lymph node evaluation and had complete prognostic information. Clinicopathological data of patients with T1-2 stage colorectal cancer treated with surgery at Peking University People's Hospital from 2017 to 2021 with complete clinical information were retrieved. We identify and confirm the risk factors for positive lymph node involvement, and the results of follow-up were analyzed. RESULTS: Age, preoperative carcinoembryonic antigen (CEA) level, perineural invasion, and primary tumor site were independent risk factors for LNM in T1-2 CRC based on the analysis of the SEER database, while tumor size and histology of mucinous carcinoma were also independent risk factors in T1 CRC. We then make the nomogram model for predicting LNM risk and showed an acceptable consistency and calibration capability. Survival analysis showed that LNM was an independent prognostic indicator of 5-year disease-specific survival (P = 0.013) and disease-free survival (P < 0.001) in patients with T1 and T2 CRC. CONCLUSION: Age, CEA level and primary tumor site should be taken into consideration before making the surgical decision in T1-2 CRC patients. The tumor size and histology of mucinous carcinoma also need to be thought about in T1 CRC. Conventional imaging tests do not appear to provide a precise assessment for this issue.


Asunto(s)
Adenocarcinoma Mucinoso , Neoplasias Colorrectales , Humanos , Antígeno Carcinoembrionario , Estadificación de Neoplasias , Metástasis Linfática/patología , Ganglios Linfáticos/cirugía , Ganglios Linfáticos/patología , Biomarcadores de Tumor , Neoplasias Colorrectales/patología
15.
Tissue Cell ; 81: 102003, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-36682224

RESUMEN

OBJECTIVE: Necrotizing enterocolitis (NEC) is a severe disease in newborns, this study aimed to investigate the protective effect of dimethyl fumarate (DMF) on NEC and its possible mechanism. METHODS: In vivo, the mice were divided into the control, NEC, and NEC+DMF group. The NEC model was established by artificial feeding, hypoxic for 4 days, and lipopolysaccharide (LPS) stimulation on day 2 and day 3. DMF (25 mg/kg/d) was administered to NEC mice on day 1 and day 3. On the 11th day, the blood and intestinal tissues of mice were taken for enzyme-linked immunosorbent assay (ELISA), pathological examination, quantitative real-time PCR (RT-qPCR), Western blot, and immunohistochemical (IHC) detection. In vitro, human colorectal cells (FHC) were induced by LPS (100 ng/mL) and was divided into the control, LPS, and LPS+DMF group. The effect of DMF (20 µM) on cell viability and TLR4 signal transduction was detected by MTT and RT-qPCR, respectively. RESULTS: Compared to the NEC mice, DMF attenuated NEC-induced weight loss and abdominal distension diarrhea in mice, and alleviated NEC-induced intestinal pathological injuries. In addition, DMF reduced the expression of IL-6, IL-1ß, TNF-α, NF-κB, and TLR4 in NEC mice intestinal tissues. Furthermore, DMF inhibited NEC-induced intestinal cell apoptosis as well as the protein expression of BCL2-Associated X (BAX), caspase-3, caspase-9, and increased Bcl-2 (B-cell lymphoma-2) expression. In vitro, DMF improved cell viability, and restrained NF-κB and TLR4 expression in LPS-induced NEC cells. CONCLUSION: DMF has a protective effect against intestine damage of NEC, which is related to the inhibition of the TLR signaling pathway, alleviating the inflammatory response.


Asunto(s)
Enterocolitis Necrotizante , FN-kappa B , Animales , Ratones , Recién Nacido , Humanos , FN-kappa B/metabolismo , Dimetilfumarato/farmacología , Receptor Toll-Like 4/metabolismo , Enterocolitis Necrotizante/tratamiento farmacológico , Enterocolitis Necrotizante/prevención & control , Enterocolitis Necrotizante/metabolismo , Lipopolisacáridos/toxicidad , Transducción de Señal , Intestinos/patología , Modelos Animales de Enfermedad
16.
Environ Geochem Health ; 45(6): 3805-3816, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-36577857

RESUMEN

Organophosphate esters (OPEs) are emerging pollutants. Currently, research on OPEs in tree rings is still limited. In this study, tree rings of five arbor species from Sichuan Province, China, were sampled to study the occurrence and distribution of six OPEs, which were quantitatively analyzed by gas chromatography-mass spectrometry (GC-MS). The total concentrations of OPEs in all samples ranged from 189.79 (Fir species) to 341.23 ng/g (Toona sinensis), with average concentration of 284.77 ± 46.66 ng/g. So, arbor could be used as good passive samplers for OPEs. The levels of OPEs among five arbor species showed no significant difference (p = 0.668 > 0.05), suggesting that the pollution status of OPEs in a region or country could be roughly assessed by any arbor tree species. In this study area, tris(2-butoxyethyl) phosphate (TBEP) was the dominant OPEs followed by tri(2-chloroethyl) phosphate (TCEP). Tris(2-ethylhexyl) phosphate (TEHP) and tri-n-butyl phosphate (TnBP) showed relatively stable concentrations in each arbor species, while the other four OPEs including TBEP, triphenyl phosphate (TPhP), tri(chloropropyl) phosphate (TCPP) and TCEP had significantly different concentrations. Interestingly, the absorption and accumulation of OPEs by tree rings of arbor species were quite different from that of inorganic elements reported by other studies.


Asunto(s)
Monitoreo del Ambiente , Retardadores de Llama , Monitoreo del Ambiente/métodos , Ésteres/análisis , Retardadores de Llama/análisis , Organofosfatos/análisis , China , Fosfatos/análisis
17.
Comb Chem High Throughput Screen ; 26(6): 1186-1195, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-35792122

RESUMEN

BACKGROUND: Necrotizing enterocolitis (NEC) is a neonatal intestinal necrotizing disease caused by various factors in newborns. Sulforaphane (SFN) has a strong anti-inflammatory ability and a certain protective effect on intestinal diseases. OBJECTIVE: NEC is a common developed gastrointestinal exigency in an untimely baby. SFN is a naturally originated isothiocyanate that has beneficial effects on the intestinal system.The purpose of this study is to study the protective effect of SFN on endoplasmic reticulum stress (ERS)-related NEC. METHODS: The newborn mice were randomly divided into control (n = 15), NEC (n = 20), and NEC+SFN (n = 18) groups. Mice in NEC and SFN+NEC groups were injected with 0.1 µl normal saline or 20 mg/kg/d SFN, respectively. After that, the weight and survival of the mice were recorded every day. Then the mice were sacrificed after 96 h of modeling; ileum tissue and blood samples were collected for qPCR, Western blot, ELISA, HE staining, TUNEL staining, and immunohistochemistry assays. RESULTS: SFN significantly inhibited the mRNA expression of BIP, CHOP, IL-1ß and IL-6, and protein expression of Bax, Caspase-3, Caspase-9 and CHOP, and promoted the expression of Bcl-2 in ER-induced NEC mice intestinal tissues (P<0.01). Meanwhile, SFN could suppress the serum levels of IL-8, IL-10, IL-6, TNF-α, and IL-1ß, and positive expression of TLR4 and NF-κB (P<0.01), and promote the serum levels of IL-10. HE staining showed that SFN alleviated the NEC intestinal tissue injury, and TUNNEL staining showed that SFN could reduce the rate of NEC apoptotic cells (P<0.01). Moreover, SFN treatment improved the body weight and survival rate in NEC mice. CONCLUSION: SFN could effectively protect against ERS-induced inflammation and apoptosis in NEC mice.


Asunto(s)
Enterocolitis Necrotizante , Mucosa Intestinal , Ratones , Animales , Mucosa Intestinal/metabolismo , Interleucina-10/metabolismo , Interleucina-10/farmacología , Interleucina-6/metabolismo , Enterocolitis Necrotizante/tratamiento farmacológico , Enterocolitis Necrotizante/metabolismo , Isotiocianatos/farmacología , Apoptosis , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Modelos Animales de Enfermedad
18.
Bioact Mater ; 22: 225-238, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-36254273

RESUMEN

Staplers have been widely used in the clinical treatment of gastrointestinal reconstruction. However, the current titanium (Ti) staple will remain in the human body permanently, resulting in some adverse effects. In this study, we developed a type of biodegradable staple for colonic anastomosis using 0.3 mm diameter magnesium (Mg) alloy wires. The wire surface was modified by micro-arc oxidation treatment (MAO) and then coated with poly-l-lactic acid (PLLA) to achieve a moderate degradation rate matching the tissue healing process. The results of tensile tests on isolated porcine colon tissue anastomosed by Mg and Ti staples showed that the anastomotic property of Mg staples was almost equal to that of Ti staples. The in vitro degradation tests indicated the dual-layer coating effectively enhanced the corrosion resistance and maintained the tensile force of the coated staple stable after 14-day immersion in the simulated colonic fluid (SCF). Furthermore, 24 beagle dogs were employed to conduct a comparison experiment using Mg-based and clinical Ti staples for 90-day implantation by ent-to-side anastomosis of the colon. The integrated structure of Mg-based staples was observed after 7 days and completely degraded after 90 days. All animals did not have anastomotic leakage and stenosis, and 12 dogs with Mg-based staples fully recovered after 90 days without differences in visceral ion levels and other side effects. The favorable performance makes this Mg-based anastomotic staple an ideal candidate for colon reconstruction.

19.
New Phytol ; 236(6): 2216-2232, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-36101507

RESUMEN

Rice production is threatened by multiple pathogens. Breeding cultivars with broad-spectrum disease resistance is necessary to maintain and improve crop production. Previously we found that overexpression of miR160a enhanced rice blast disease resistance. However, it is unclear whether miR160a also regulates resistance against other pathogens, and what the downstream signaling pathways are. Here, we demonstrate that miR160a positively regulates broad-spectrum resistance against the causative agents of blast, leaf blight and sheath blight in rice. Mutations of miR160a-targeted Auxin Response Factors result in different alteration of resistance conferred by miR160a. miR160a enhances disease resistance partially by suppressing ARF8, as mutation of ARF8 in MIM160 background partially restores the compromised resistance resulting from MIM160. ARF8 protein binds directly to the promoter and suppresses the expression of WRKY45, which acts as a positive regulator of rice immunity. Mutation of WRKY45 compromises the enhanced blast resistance and bacterial leaf blight resistance conferred by arf8 mutant. Overall, our results reveal that a microRNA coordinates rice broad-spectrum disease resistance by suppressing multiple target genes that play different roles in disease resistance, and uncover a new regulatory pathway mediated by the miR160a-ARF8 module. These findings provide new resources to potentially improve disease resistance for breeding in rice.


Asunto(s)
Magnaporthe , Oryza , Resistencia a la Enfermedad/genética , Magnaporthe/metabolismo , Oryza/metabolismo , Enfermedades de las Plantas/microbiología , Proteínas de Plantas/metabolismo , Fitomejoramiento
20.
Front Genet ; 13: 976007, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36176287

RESUMEN

Faced with the high heterogeneity and poor prognosis of colorectal cancer (CRC), this study sought to find new predictive prognostic strategies to improve the situation. Cuproptosis is a novel cell death mechanism that relies on copper regulation. However, the role of cuproptosis-related gene (CRG) in CRC remains to be elucidated. In this study, we comprehensively assessed the CRG landscape in CRC based on The Cancer Genome Atlas (TCGA). We identified differential expression and genetic alterations of CRG in CRC. CRG is highly correlated with initiation, progression, prognosis, and immune infiltration of CRC. We construct a risk score signature containing 3 CRGs based on LASSO. We explored the correlation of CRG-Score with clinicopathological features of CRC. Age, stage, and CRG-Score were integrated to construct a nomogram. The nomogram has robust predictive performance. We also understand the correlation of CRG-Score with CRC immune landscape. CRG-Score can effectively predict the immune landscape of CRC patients. Low-risk CRC patients have greater immunogenicity and higher immune checkpoint expression. Low-risk CRC patients may be better candidates for immunotherapy. At the same time, we also predicted more sensitive drugs in the high-risk CRC patients. In conclusion, the CRG risk score signature is a strong prognostic marker and may help provide new insights into the treatment of individuals with CRC.

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