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1.
Hypertens Res ; 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38750218

RESUMO

Phenotypic shift of vascular smooth muscle cells (VSMCs) plays a key role in intimal hyperplasia, especially in patients with diabetes mellitus (DM). This study aimed to investigate the role of dynamin-related protein 1 (DRP1) in mitochondrial fission-mediated VSMC phenotypic shift and to clarify whether DRP1 is the therapeutic target of isoliquiritigenin (ISL). Wire injury of carotid artery or platelet-derived growth factor treatment was performed in DM mice or high-glucose cultured human aortic smooth muscle cells (HASMCs), respectively. The effects of DRP1 silencing on DM-induced intimal hyperplasia were investigated both in vivo and in vitro. Phenotypic shift of HASMCs was evaluated by detection of reactive oxygen species (ROS) generation, cell viability, and related protein expressions. The effects of ISL on DM-induced intimal hyperplasia were evaluated both in vivo and in vitro. DRP1 silencing and ISL treatment attenuated DM-induced intimal hyperplasia with reduced ROS generation, cell viability, and VSMC dedifferentiation. The GTPase domain of DRP1 protein played a critical role in mitochondrial fission in DM-induced VSMC phenotypic shift. Cellular experiments showed that ISL inhibited mitochondrial fission and reduced the GTPase activity of DRP1, which was achieved by the directly binding to K216 of the DRP1 GTPase domain. ISL attenuated mouse intimal hyperplasia by reducing GTPase activity of DRP1 and inhibiting mitochondrial fission in vivo. In conclusion, increased GTPase activity of DRP1 aggregated DM-induced intimal hyperplasia by increasing mitochondrial fission-mediated VSMC phenotypic shift. ISL attenuated mouse intimal hyperplasia by reducing DRP1 GTPase activity and inhibiting mitochondrial fission of VSMCs.

2.
Acta Biomater ; 181: 469-482, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38723926

RESUMO

Medium-entropy alloys (MEAs) typically exhibit outstanding mechanical properties, but their high Young's modulus results in restricted clinical applications. Mismatched Young's modulus between implant materials and human bones can lead to "stress shielding" effects, leading to implant failure. In contrast, ß-Ti alloys demonstrate a lower Young's modulus compared to MEAs, albeit with lower strength. In the present study, based on the bimodal grain size distribution (BGSD) strategy, a series of high-performance TiZrNbTa/Ti composites are obtained by combining TiZrNbTa MEA powders with nano-scale grain sizes and commercially pure Ti (CP-Ti) powders with micro-scale grain sizes. Concurrently, Zr, Nb, and Ta that are ß-Ti stabilizer elements diffuse into Ti, inducing an isomorphous transformation in Ti from the high Young's modulus α-Ti phase to the low Young's modulus ß-Ti phase at room temperature, optimizing the mechanical biocompatibility. The TiZrNbTa/ß-Ti composite demonstrates a yield strength of 1490 ± 83 MPa, ductility of 20.7 % ± 2.9 %, and Young's modulus of 87.6 ± 1.6 GPa. Notably, the yield strength of the TiZrNbTa/ß-Ti composite surpasses that of sintered CP-Ti by 2.6-fold, and its ductility outperforms TiZrNbTa MEA by 2.3-fold. The Young's modulus of the TiZrNbTa/ß-Ti composite is reduced by 28 % and 36 % compared to sintered CP-Ti and TiZrNbTa MEA, respectively. Additionally, it demonstrates superior biocompatibility compared to CP-Ti plate, sintered CP-Ti, and TiZrNbTa MEA. With a good combination of mechanical properties and biocompatibility, the TiZrNbTa/ß-Ti composite exhibits significant potential for clinical applications as metallic biomaterials. STATEMENT OF SIGNIFICANCE: This work combines TiZrNbTa MEA with nano-grains and commercially pure Ti with micro-grains to fabricate a TiZrNbTa/ß-Ti composite with bimodal grain-size, which achieves a yield strength of 1490 ± 83 MPa and a ductility of 20.7 % ± 2.9 %. Adhering to the ISO 10993-5 standard, the TiZrNbTa/ß-Ti composite qualifies as a non-cytotoxic material, achieving a Class 0 cytotoxicity rating and demonstrating outstanding biocompatibility akin to commercially pure Ti. Drawing on element diffusion, Zr, Nb, and Ta serve not only as solvent atoms to achieve solid-solution strengthening but also as stabilizers for the transformation of the ß-Ti crystal structure. This work offers a novel avenue for designing advanced biomedical Ti alloys with elevated strength and plasticity alongside a reduced Young's modulus.


Assuntos
Ligas , Materiais Biocompatíveis , Teste de Materiais , Titânio , Titânio/química , Titânio/farmacologia , Ligas/química , Ligas/farmacologia , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Animais , Módulo de Elasticidade , Humanos , Nióbio/química , Nióbio/farmacologia , Zircônio/química , Zircônio/farmacologia , Transição de Fase , Camundongos
3.
Nat Commun ; 15(1): 4538, 2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38806466

RESUMO

The superconducting gap symmetry is crucial in understanding the underlying superconductivity mechanism. Angle-resolved photoemission spectroscopy (ARPES) has played a key role in determining the gap symmetry in unconventional superconductors. However, it has been considered so far that ARPES can only measure the magnitude of the superconducting gap but not its phase; the phase has to be detected by other phase-sensitive techniques. Here we propose a method to directly detect the superconducting gap sign by ARPES. This method is successfully validated in a cuprate superconductor Bi2Sr2CaCu2O8+δ with a well-known d-wave gap symmetry. When two bands have a strong interband interaction, the resulted electronic structures in the superconducting state are sensitive to the relative gap sign between the two bands. Our present work provides an approach to detect the gap sign and can be applied to various superconductors, particularly those with multiple orbitals like the iron-based superconductors.

4.
Stem Cell Res Ther ; 15(1): 155, 2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38816841

RESUMO

In the past decade, intestinal organoid technology has paved the way for reproducing tissue or organ morphogenesis during intestinal physiological processes in vitro and studying the pathogenesis of various intestinal diseases. Intestinal organoids are favored in drug screening due to their ability for high-throughput in vitro cultivation and their closer resemblance to patient genetic characteristics. Furthermore, as disease models, intestinal organoids find wide applications in screening diagnostic markers, identifying therapeutic targets, and exploring epigenetic mechanisms of diseases. Additionally, as a transplantable cellular system, organoids have played a significant role in the reconstruction of damaged epithelium in conditions such as ulcerative colitis and short bowel syndrome, as well as in intestinal material exchange and metabolic function restoration. The rise of interdisciplinary approaches, including organoid-on-chip technology, genome editing techniques, and microfluidics, has greatly accelerated the development of organoids. In this review, VOSviewer software is used to visualize hot co-cited journal and keywords trends of intestinal organoid firstly. Subsequently, we have summarized the current applications of intestinal organoid technology in disease modeling, drug screening, and regenerative medicine. This will deepen our understanding of intestinal organoids and further explore the physiological mechanisms of the intestine and drug development for intestinal diseases.


Assuntos
Organoides , Organoides/metabolismo , Organoides/citologia , Humanos , Intestinos/citologia , Animais , Medicina Regenerativa/métodos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/citologia
5.
Dalton Trans ; 2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38804223

RESUMO

Correction for 'Single molecule magnet features in luminescent lanthanide coordination polymers with heptacoordinate Dy/Yb(III) ions as nodes' by Xiang-Tao Dong et al., Dalton Trans., 2023, 52, 12686-12694, https://doi.org/10.1039/D3DT02106H.

6.
Mol Med ; 30(1): 58, 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38720283

RESUMO

BACKGROUND: Vascular calcification (VC) is a complication in diabetes mellitus (DM) patients. Osteogenic phenotype switching of vascular smooth muscle cells (VSMCs) plays a critical role in diabetes-related VC. Mitophagy can inhibit phenotype switching in VSMCs. This study aimed to investigate the role of the glucagon-like peptide-1 receptor (GLP-1R) agonist exendin 4 (EX4) in mitophagy-induced phenotype switching. MATERIALS AND METHODS: The status of VC in T2DM mice was monitored using Von Kossa and Alizarin Red S (ARS) staining in mouse aortic tissue. Human aortic smooth muscle cells were cultured in high glucose (HG) and ß-glycerophosphate (ß-GP) conditioned medium. Accumulation of LC3B and p62 was detected in the mitochondrial fraction. The effect of EX4 in vitro and in vivo was investigated by knocking down AMPKα1. RESULTS: In diabetic VC mice, EX4 decreased the percentage of von Kossa/ARS positive area. EX4 inhibited osteogenic differentiation of HG/ß-GP-induced VSMCs. In HG/ß-GP-induced VSMCs, the number of mitophagosomes was increased, whereas the addition of EX4 restored mitochondrial function, increased the number of mitophagosome-lysosome fusions, and reduced p62 in mitochondrial frictions. EX4 increased the phosphorylation of AMPKα (Thr172) and ULK1 (Ser555) in HG/ß-GP-induced VSMCs. After knockdown of AMPKα1, ULK1 could not be activated by EX4. The accumulation of LC3B and p62 could not be reduced after AMPKα1 knockdown. Knockdown of AMPKα1 negated the therapeutic effects of EX4 on VC of diabetic mice. CONCLUSION: EX4 could promote mitophagy by activating the AMPK signaling pathway, attenuate insufficient mitophagy, and thus inhibit the osteogenic phenotype switching of VSMCs.


Assuntos
Proteínas Quinases Ativadas por AMP , Exenatida , Receptor do Peptídeo Semelhante ao Glucagon 1 , Mitofagia , Transdução de Sinais , Calcificação Vascular , Animais , Mitofagia/efeitos dos fármacos , Calcificação Vascular/etiologia , Calcificação Vascular/metabolismo , Calcificação Vascular/tratamento farmacológico , Transdução de Sinais/efeitos dos fármacos , Camundongos , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Receptor do Peptídeo Semelhante ao Glucagon 1/metabolismo , Masculino , Proteínas Quinases Ativadas por AMP/metabolismo , Humanos , Exenatida/farmacologia , Exenatida/uso terapêutico , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/efeitos dos fármacos , Músculo Liso Vascular/patologia , Miócitos de Músculo Liso/metabolismo , Miócitos de Músculo Liso/efeitos dos fármacos , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/tratamento farmacológico , Modelos Animais de Doenças , Camundongos Endogâmicos C57BL
7.
Artigo em Inglês | MEDLINE | ID: mdl-38598383

RESUMO

A long-standing topic in artificial intelligence is the effective recognition of patterns from noisy images. In this regard, the recent data-driven paradigm considers 1) improving the representation robustness by adding noisy samples in training phase (i.e., data augmentation) or 2) pre-processing the noisy image by learning to solve the inverse problem (i.e., image denoising). However, such methods generally exhibit inefficient process and unstable result, limiting their practical applications. In this paper, we explore a non-learning paradigm that aims to derive robust representation directly from noisy images, without the denoising as pre-processing. Here, the noise-robust representation is designed as Fractional-order Moments in Radon space (FMR), with also beneficial properties of orthogonality and rotation invariance. Unlike earlier integer-order methods, our work is a more generic design taking such classical methods as special cases, and the introduced fractional-order parameter offers time-frequency analysis capability that is not available in classical methods. Formally, both implicit and explicit paths for constructing the FMR are discussed in detail. Extensive simulation experiments and robust visual applications are provided to demonstrate the uniqueness and usefulness of our FMR, especially for noise robustness, rotation invariance, and time-frequency discriminability.

8.
BMC Emerg Med ; 24(1): 69, 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38649815

RESUMO

OBJECTIVE: This survey aims to comprehensively understand occupational burnout among pre-hospital emergency medical personnel and explore associated risk factors. METHODS: A cross-sectional online survey using a census method was conducted between 15 July, 2023, and ends on 14 August, 2023, in Chengdu, SiChuan province, China. The questionnaire included general demographic information, the Maslach Burnout Inventory-General Survey (MBI-GS) with 15 items, and the Fatigue Scale-14 (FS-14) with 14 items. Univariate analysis was conducted on all variables, followed by multivariate logistic regression models to examine the associations between occupational burnout and the risk factors. RESULTS: A total of 2,299 participants,99.57% completed the survey effectively The participants were from 166 medical institutions in Chengdu, comprising 1,420 nurses (61.50%) and 889 clinical doctors (38.50%). A total of 33.36% participants experienced burnout, predominantly mild (30.27%), followed by moderate (2.78%) and severe (0.3%). Physicians, higher fatigue scores, age, work experience appeared to be related to burnout. Logistic regression models revealed that individuals aged over 50 were less prone to experience burnout compared to medical staff aged 18-30 (OR: 0.269, 95% CI: 0.115-0.627, p = 0.002). Physicians were more prone to experience burnout compared to nursing staff (OR: 0.690, 95% CI: 0.531-0.898, p = 0.006). Those with 0-5 years of experience were more prone to experience burnout compared to those with 6-10 years or over 15 years of experience (OR: 0.734, 95% CI: 0.547-0.986, p = 0.040; OR: 0.559, 95% CI: 0.339-0.924, p = 0.023). Additionally, for each 1-point increase in the fatigue score, the likelihood of burnout in medical staff increased by 1.367 times (OR: 1.367, 95% CI: 1.323-1.412, p < 0.0001). CONCLUSION: Pre-hospital emergency medical personnel demonstrate a notable prevalence of mild job burnout. These results provide a groundwork for future focus on the various stages of job burnout within pre-hospital emergency staff, alerting hospital and departmental managers to promptly address the mental well-being of their personnel and intervene as needed.


Assuntos
Esgotamento Profissional , Humanos , Esgotamento Profissional/epidemiologia , Esgotamento Profissional/psicologia , Estudos Transversais , Masculino , Feminino , Adulto , China/epidemiologia , Pessoa de Meia-Idade , Inquéritos e Questionários , Fatores de Risco , Adulto Jovem , Auxiliares de Emergência/psicologia , Fadiga/epidemiologia , Médicos/psicologia , Adolescente , Modelos Logísticos
9.
World J Clin Cases ; 12(10): 1799-1803, 2024 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-38660075

RESUMO

BACKGROUND: The precise mechanism by which severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) impacts the central nervous system remains unclear, with manifestations spanning from mild symptoms (e.g., olfactory and gustatory deficits, hallucinations, and headache) to severe complications (e.g., stroke, seizures, encephalitis, and neurally demyelinating lesions). The occurrence of single-pass subdural effusion, as described below, is extremely rare. CASE SUMMARY: A 56-year-old male patient presented with left-sided limb weakness and slurred speech as predominant clinical symptoms. Through comprehensive imaging and diagnostic assessments, he was diagnosed with cerebral infarction complicated by hemorrhagic transformation affecting the right frontal, temporal, and parietal regions. In addition, an intracranial infection with SARS-CoV-2 was identified during the rehabilitation process; consequently, an idiopathic subdural effusion developed. Remarkably, the subdural effusion underwent absorption within 6 d, with no recurrence observed during the 3-month follow-up. CONCLUSION: Subdural effusion is a potentially rare intracranial complication associated with SARS-CoV-2 infection.

10.
Nat Aging ; 4(4): 527-545, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38594460

RESUMO

Limited understanding exists regarding how aging impacts the cellular and molecular aspects of the human ovary. This study combines single-cell RNA sequencing and spatial transcriptomics to systematically characterize human ovarian aging. Spatiotemporal molecular signatures of the eight types of ovarian cells during aging are observed. An analysis of age-associated changes in gene expression reveals that DNA damage response may be a key biological pathway in oocyte aging. Three granulosa cells subtypes and five theca and stromal cells subtypes, as well as their spatiotemporal transcriptomics changes during aging, are identified. FOXP1 emerges as a regulator of ovarian aging, declining with age and inhibiting CDKN1A transcription. Silencing FOXP1 results in premature ovarian insufficiency in mice. These findings offer a comprehensive understanding of spatiotemporal variability in human ovarian aging, aiding the prioritization of potential diagnostic biomarkers and therapeutic strategies.


Assuntos
Fatores de Transcrição Forkhead , Ovário , Animais , Feminino , Humanos , Camundongos , Fatores de Transcrição Forkhead/genética , Perfilação da Expressão Gênica , Células da Granulosa/metabolismo , Oócitos/metabolismo , Ovário/metabolismo , Proteínas Repressoras/metabolismo , Fatores de Transcrição/metabolismo , Insuficiência Ovariana Primária/genética , Insuficiência Ovariana Primária/metabolismo , Inibidor de Quinase Dependente de Ciclina p21/genética , Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Envelhecimento/genética
11.
Front Biosci (Landmark Ed) ; 29(3): 129, 2024 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-38538256

RESUMO

BACKGROUND: The survival rate of hepatocellular carcinoma (HCC) is low and the prognosis is poor. Metabolic reprogramming is still an emerging hallmark of cancer, and reprogramming of cholesterol metabolism plays a crucial action in tumor pathogenesis. Increasing evidence suggests that cholesterol metabolism affects the cell proliferation, invasion, migration, and resistance to chemotherapy of HCC. To date, no long noncoding RNA (lncRNA) signature associated with cholesterol metabolism has been developed to predict the outcome of patients with HCC. METHODS: The RNA-seq data as well as the prognostic and clinical data were obtained from The Cancer Genome Atlas (TCGA) database. We conducted univariate and multivariate analyses to assess cholesterol metabolism-related lncRNAs correlated with the prognosis of patients with HCC in order to construct a prognostic signature. Functional differences between low- and high-risk groups were investigated using genomic enrichment analysis (GSEA). Kaplan-Meier (KM) curves were applied to explore the overall survival (OS) of the low- and high-risk groups. Single-sample genomic enrichment analysis (ssGSEA) was applied to investigate the association between this predictive signature and immune function. We subsequently examined how this signature relates to treatment response in HCC patients. RESULTS: A prognostic signature comprising six lncRNAs related to cholesterol metabolism was constructed (AC124798.1, AL031985.3, AC103760.1, NRAV, WAC-AS1 and AC022613.1). We found that low-risk groups showed a better prognosis than high-risk groups. In HCC patients, the cholesterol metabolism-related lncRNA signature may be served as an independent prognostic factor. Cholesterol metabolism-related lncRNA signature had higher diagnostic efficiency compared to clinicopathologic variables. After stratifying patients according to different clinicopathological variables, patients with low-risk had a longer OS compared with high-risk patients. The ssGSEA demonstrated that this signature was closely related to the immune status of HCC patients. GSEA analysis demonstrated that immune- and tumor-related pathways were predominantly enriched in the high-risk group. High-risk patients were more responsive to immune checkpoint inhibitors (ICIs) and conventional chemotherapeutic agents. CONCLUSIONS: This cholesterol metabolism-related lncRNA signature can predict the prognosis of HCC patients and guide the clinical management of HCC patients, including immunotherapy.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , RNA Longo não Codificante , Humanos , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/terapia , RNA Longo não Codificante/genética , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/terapia , Imunoterapia , Colesterol
12.
Adv Healthc Mater ; : e2304536, 2024 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-38519046

RESUMO

Intense and persistent oxidative stress, excessive inflammation, and impaired angiogenesis severely hinder diabetic wound healing. Bioactive hydrogel dressings with immunoregulatory and proangiogenic properties have great promise in treating diabetic wounds. However, the therapeutic effects of dressings always depend on drugs with side effects, expensive cytokines, and cell therapies. Herein, a novel dynamic borate-bonds crosslinked hybrid multifunctional hydrogel dressings with photothermal properties are developed to regulate the microenvironment of diabetic wound sites and accelerate the whole process of its healing without additional medication. The hydrogel is composed of phenylboronic acid-modified chitosan and hyaluronic acid (HA) crosslinked by tannic acid (TA) through borate bonds and Prussian blue nanoparticles (PBNPs) with photothermal response characteristics are embedded in the polymer networks. The results indicate hydrogels show inherent broad-spectrum antioxidative activities through the integrated interaction of borate bonds, TA, and PBNPs. Meanwhile, combined with the regulation of macrophage phenotype by HA, the inflammatory microenvironment of diabetic wounds is transformed. Moreover, the angiogenesis is then enhanced by the mild photothermal effect of PBNPs, followed by promoted epithelialization and collagen deposition. In summary, this hybrid hydrogel system accelerates all stages of wound repair through antioxidative stress, immunomodulation, and proangiogenesis, showing great potential applications in diabetic wound management.

13.
J Opt Soc Am A Opt Image Sci Vis ; 41(2): 157-164, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38437328

RESUMO

Feature point matching is one of the fundamental tasks in binocular vision. It directly affects the accuracy and quality of 3D reconstruction. This study proposes a directional region-based feature point matching algorithm based on the SURF algorithm to improve the accuracy of feature point matching. First, same-name points are selected as the matching reference points in the left and right images. Then, the SURF algorithm is used to extract feature points and construct the SURF feature point descriptors. During the matching process, the location relationship between the query feature point and the reference point in the left image is directed to determine the corresponding matching region in the right image. Then, the matching is completed within this region based on Euclidean distance. Finally, the grid-based motion statistics algorithm is used to eliminate mismatches. Experimental results show that the proposed algorithm can substantially improve the matching accuracy and the number of valid matched points, particularly in the presence of a large amount of noise and interference. It also exhibits good robustness and stability.

14.
Chem Biol Drug Des ; 103(2): e14436, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38395608

RESUMO

Neuroinflammation contributes to neurological dysfunction in the patients who suffer from subarachnoid hemorrhage (SAH). Isoliquiritigenin (ISL) is a bioactive component extracted from Genus Glycyrrhiza. This work is to investigate whether ISL ameliorates neuroinflammation after SAH. In this study, intravascular perforation of male Sprague-Dawley rats was used to establish a SAH model. ISL was administered by intraperitoneal injection 6 h after SAH in rats. The mortality, SAH grade, neurological score, brain water content, and blood-brain barrier (BBB) permeability were examined at 24 h after the treatment. Expressions of tumor necrosis factor-α, interleukin-6, Iba-1, and MPO were measured by quantitative real-time polymerase chain reaction (qRT-PCR). Besides, the expression levels of NF-κB p65 and NLRP3, ASC, caspase-1, IL-1ß, and IL-18 were analyzed by western blot. The experimental data suggested that ISL treatment could ameliorate neurological impairment, attenuate brain edema, and ameliorate BBB injury after SAH in rats. ISL treatment repressed the expression of proinflammatory cytokines TNF-α and IL-6, and meanwhile inhibited the expression of Iba-1 and MPO. ISL also repressed NF-κB p65 expression as well as the transport from the cytoplasm to the nucleus. In addition, ISL significantly suppressed the expression levels of NLR family pyrin domain containing 3 (NLRP3), ASC, caspase-1, IL-1ß, and IL-18. These findings suggest that ISL inactivates NLRP3 pathway by inhibiting NF-κB p65 translocation, thereby repressing the neuroinflammation after SAH, and it is a potential drug for the treatment of SAH.


Assuntos
Lesões Encefálicas , Chalconas , Hemorragia Subaracnóidea , Humanos , Ratos , Masculino , Animais , NF-kappa B/metabolismo , Hemorragia Subaracnóidea/complicações , Hemorragia Subaracnóidea/tratamento farmacológico , Inflamassomos/metabolismo , Ratos Sprague-Dawley , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Interleucina-18/uso terapêutico , Doenças Neuroinflamatórias , Lesões Encefálicas/tratamento farmacológico , Lesões Encefálicas/metabolismo , Lesões Encefálicas/patologia , Fator de Necrose Tumoral alfa/genética , Caspases/uso terapêutico
15.
J Pept Sci ; 30(7): e3572, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38396336

RESUMO

Hairy tofu is a famous Chinese snack that is made from soybeans and rich in various nutrients. In order to further explore the antioxidant peptides of hairy tofu hydrolysates, seven proteases were used to hydrolyze hairy tofu. The results of in vitro radical scavenging activity showed that hairy tofu hydrolysates obtained by pancreatin exhibited the highest antioxidant activity. After Sephadex G-25 gel filtration and reversed-phase high-performance liquid chromatography (RP-HPLC), 97 peptides were identified in the most antioxidant fraction using liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS). Among them, nine peptides were synthesized and their antioxidant activities were assessed using a H2O2-induced oxidative 293T cell model. Finally, four peptides (QCESHK, LAWNEGR, NLQGENEWDQK, and FTEMWR) at concentrations of < 50 µg/ml significantly decreased the malondialdehyde content compared with the model group, displaying in vivo antioxidant activity and low cytotoxicity. Overall, this research provided the choice of using hairy tofu peptides as antioxidant products in the pharmaceutical and food industries.


Assuntos
Antioxidantes , Peptídeos , Humanos , Antioxidantes/química , Antioxidantes/farmacologia , Cromatografia Líquida de Alta Pressão , Células HEK293 , Peróxido de Hidrogênio , Hidrólise , Peptídeos/química , Peptídeos/farmacologia , Peptídeos/isolamento & purificação , Alimentos de Soja/análise
16.
Zhejiang Da Xue Xue Bao Yi Xue Ban ; 53(1): 58-63, 2024 Feb 15.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-38413220

RESUMO

A 70-year-old man had radical surgery for colon cancer one year before the symptoms of memory loss and decreasing cognitive function. Subsequent magnetic resonance imaging revealed a brain mass, which was surgically resected and confirmed to be metastatic intestinal adenocarcinoma. Immunohistochemistry of the primary tumor and brain metastasis showed mismatch repair deficiency. The patient received adjuvant chemotherapy after surgery. However, the brain metastasis relapsed one month after the last chemotherapy. Genetic testing on the resected colon tumor samples confirmed microsatellite instability-high with a high tumor mutation burden by 77.7 muts/Mb. The patient was subsequently treated with programmed death-1 (PD-1) monoclonal antibody pembrolizumab (keytruda). The brain metastatic lesions were completely shrunk, and a complete clinical response was achieved.


Assuntos
Adenocarcinoma , Antineoplásicos Imunológicos , Neoplasias Encefálicas , Neoplasias do Colo , Neoplasias Colorretais , Síndromes Neoplásicas Hereditárias , Masculino , Humanos , Idoso , Receptor de Morte Celular Programada 1/genética , Receptor de Morte Celular Programada 1/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Mutação , Antineoplásicos Imunológicos/uso terapêutico
18.
Curr Med Sci ; 44(1): 134-143, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38273178

RESUMO

OBJECTIVE: SUMO-specific protease 3 (SENP3), a member of the SUMO-specific protease family, reverses the SUMOylation of SUMO-2/3 conjugates. Dysregulation of SENP3 has been proven to be involved in the development of various tumors. However, its role in mantle cell lymphoma (MCL), a highly aggressive lymphoma, remains unclear. This study was aimed to elucidate the effect of SENP3 in MCL. METHODS: The expression of SENP3 in MCL cells and tissue samples was detected by RT-qPCR, Western blotting or immunohistochemistry. MCL cells with stable SENP3 knockdown were constructed using short hairpin RNAs. Cell proliferation was assessed by CCK-8 assay, and cell apoptosis was determined by flow cytometry. mRNA sequencing (mRNA-seq) was used to investigate the underlying mechanism of SENP3 knockdown on MCL development. A xenograft nude mouse model was established to evaluate the effect of SENP3 on MCL growth in vivo. RESULTS: SENP3 was upregulated in MCL patient samples and cells. Knockdown of SENP3 in MCL cells inhibited cell proliferation and promoted cell apoptosis. Meanwhile, the canonical Wnt signaling pathway and the expression of Wnt10a were suppressed after SENP3 knockdown. Furthermore, the growth of MCL cells in vivo was significantly inhibited after SENP3 knockdown in a xenograft nude mouse model. CONCLUSION: SENP3 participants in the development of MCL and may serve as a therapeutic target for MCL.


Assuntos
Linfoma de Célula do Manto , Adulto , Animais , Humanos , Camundongos , Apoptose/genética , Cisteína Endopeptidases/genética , Cisteína Endopeptidases/metabolismo , Modelos Animais de Doenças , Linfoma de Célula do Manto/genética , Linfoma de Célula do Manto/tratamento farmacológico , Linfoma de Célula do Manto/patologia , Camundongos Nus , Proteínas do Tecido Nervoso , Peptídeo Hidrolases/uso terapêutico , RNA Mensageiro , Proteínas Wnt/uso terapêutico
19.
IEEE J Biomed Health Inform ; 28(2): 917-928, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38079366

RESUMO

Diffusion-weighted imaging (DWI) has been extensively explored in guiding the clinic management of patients with breast cancer. However, due to the limited resolution, accurately characterizing tumors using DWI and the corresponding apparent diffusion coefficient (ADC) is still a challenging problem. In this paper, we aim to address the issue of super-resolution (SR) of ADC images and evaluate the clinical utility of SR-ADC images through radiomics analysis. To this end, we propose a novel double transformer-based network (DTformer) to enhance the resolution of ADC images. More specifically, we propose a symmetric U-shaped encoder-decoder network with two different types of transformer blocks, named as UTNet, to extract deep features for super-resolution. The basic backbone of UTNet is composed of a locally-enhanced Swin transformer block (LeSwin-T) and a convolutional transformer block (Conv-T), which are responsible for capturing long-range dependencies and local spatial information, respectively. Additionally, we introduce a residual upsampling network (RUpNet) to expand image resolution by leveraging initial residual information from the original low-resolution (LR) images. Extensive experiments show that DTformer achieves superior SR performance. Moreover, radiomics analysis reveals that improving the resolution of ADC images is beneficial for tumor characteristic prediction, such as histological grade and human epidermal growth factor receptor 2 (HER2) status.


Assuntos
Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/diagnóstico por imagem , Imagem de Difusão por Ressonância Magnética , Fontes de Energia Elétrica , Radiômica , Processamento de Imagem Assistida por Computador
20.
Adv Healthc Mater ; 13(1): e2301885, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37702116

RESUMO

The healing of diabetic wounds is hindered by various factors, including bacterial infection, macrophage dysfunction, excess proinflammatory cytokines, high levels of reactive oxygen species, and sustained hypoxia. These factors collectively impede cellular behaviors and the healing process. Consequently, this review presents intelligent hydrogels equipped with multifunctional capacities, which enable them to dynamically respond to the microenvironment and accelerate wound healing in various ways, including stimuli -responsiveness, injectable self-healing, shape -memory, and conductive and real-time monitoring properties. The relationship between the multiple functions and wound healing is also discussed. Based on the microenvironment of diabetic wounds, antibacterial, anti-inflammatory, immunomodulatory, antioxidant, and pro-angiogenic strategies are combined with multifunctional hydrogels. The application of multifunctional hydrogels in the repair of diabetic wounds is systematically discussed, aiming to provide guidelines for fabricating hydrogels for diabetic wound healing and exploring the role of intelligent hydrogels in the therapeutic processes.


Assuntos
Antibacterianos , Diabetes Mellitus , Pé Diabético , Hidrogéis , Humanos , Antibacterianos/uso terapêutico , Antioxidantes , Citocinas , Condutividade Elétrica , Hidrogéis/farmacologia , Pé Diabético/tratamento farmacológico
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