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1.
Nanoscale Horiz ; 2024 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-39034818

RESUMO

We report two previously undiscovered phases of GeTe including the sphalerite (c-) phase and the hexagonal (h-) phase with interlayer van der Waals gaps. A polymorphic phase transformation from rhombohedral α-GeTe to c- and h-GeTe at near room temperature is first realized via electron beam irradiation. Their underlying thermodynamics and kinetics are illustrated using the in situ heating experiments and molecular dynamics simulations. Density-functional theory calculations indicate that c-GeTe exhibits typical metallic behavior and h-GeTe is a narrow-gap semiconductor with a strong spin-orbital coupling effect. Our findings shed light on a strategy for designing GeTe-based quantum devices compromising nanopillars and heterostructures via an atomic-scale electron beam lithography technique.

2.
Diabetologia ; 2024 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-39037604

RESUMO

AIMS/HYPOTHESIS: The relationship between metabolic dysfunction-associated steatotic liver disease (MASLD) and type 2 diabetes mellitus, insulin resistance and the metabolic syndrome is well established. While zinc finger BED-type containing 3 (ZBED3) has been linked to type 2 diabetes mellitus and the metabolic syndrome, its role in MASLD remains unclear. In this study, we aimed to investigate the function of ZBED3 in the context of MASLD. METHODS: Expression levels of ZBED3 were assessed in individuals with MASLD, as well as in cellular and animal models of MASLD. In vitro and in vivo analyses were conducted using a cellular model of MASLD induced by NEFA and an animal model of MASLD induced by a high-fat diet (HFD), respectively, to investigate the role of ZBED3 in MASLD. ZBED3 expression was increased by lentiviral infection or tail-vein injection of adeno-associated virus. RNA-seq and bioinformatics analysis were employed to examine the pathways through which ZBED3 modulates lipid accumulation. Findings from these next-generation transcriptome sequencing studies indicated that ZBED3 controls SREBP1c (also known as SREBF1; a gene involved in fatty acid de novo synthesis); thus, co-immunoprecipitation and LC-MS/MS were utilised to investigate the molecular mechanisms by which ZBED3 regulates the sterol regulatory element binding protein 1c (SREBP1c). RESULTS: In this study, we found that ZBED3 was significantly upregulated in the liver of individuals with MASLD and in MASLD animal models. ZBED3 overexpression promoted NEFA-induced triglyceride accumulation in hepatocytes in vitro. Furthermore, the hepatocyte-specific overexpression of Zbed3 promoted hepatic steatosis. Conversely, the hepatocyte-specific knockout of Zbed3 resulted in resistance of HFD-induced hepatic steatosis. Mechanistically, ZBED3 interacts directly with polypyrimidine tract-binding protein 1 (PTBP1) and affects its binding to the SREBP1c mRNA precursor to regulate SREBP1c mRNA stability and alternative splicing. CONCLUSIONS/INTERPRETATION: This study indicates that ZBED3 promotes hepatic steatosis and serves as a critical regulator of the progression of MASLD. DATA AVAILABILITY: RNA-seq data have been deposited in the NCBI Gene Expression Omnibus ( www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE231875 ). MS proteomics data have been deposited to the ProteomeXchange Consortium via the iProX partner repository ( https://proteomecentral.proteomexchange.org/cgi/GetDataset?ID=PXD041743 ).

3.
Nat Commun ; 15(1): 6057, 2024 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-39025843

RESUMO

Although molecular vibronic spectra generation is pivotal for chemical analysis, tackling such exponentially complex tasks on classical computers remains inefficient. Quantum simulation, though theoretically promising, faces technological challenges in experimentally extracting vibronic spectra for molecules with multiple modes. Here, we propose a nontrivial algorithm to generate the vibronic spectra using states with zero displacements (squeezed vacuum states) coupled to a linear optical network, offering ease of experimental implementation. We also fabricate an integrated quantum photonic microprocessor chip as a versatile simulation platform containing 16 modes of single-mode squeezed vacuum states and a fully programmable interferometer network. Molecular vibronic spectra of formic acid and thymine under the Condon approximation are simulated using the quantum microprocessor chip with high reconstructed fidelity ( > 92%). Furthermore, vibronic spectra of naphthalene, phenanthrene, and benzene under the non-Condon approximation are also experimentally simulated. Such demonstrations could pave the way for solving complicated quantum chemistry problems involving vibronic spectra and computational tasks beyond the reach of classical computers.

4.
Mediators Inflamm ; 2024: 3282679, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38962170

RESUMO

Ulcerative colitis (UC) is a chronic intestinal inflammatory disease with complex etiology. Interleukin-35 (IL-35), as a cytokine with immunomodulatory function, has been shown to have therapeutic effects on UC, but its mechanism is not yet clear. Therefore, we constructed Pichia pastoris stably expressing IL-35 which enables the cytokines to reach the diseased mucosa, and explored whether upregulation of T-cell protein tyrosine phosphatase (TCPTP) in macrophages is involved in the mechanisms of IL-35-mediated attenuation of UC. After the successful construction of engineered bacteria expressing IL-35, a colitis model was successfully induced by giving BALB/c mice a solution containing 3% dextran sulfate sodium (DSS). Mice were treated with Pichia/IL-35, empty plasmid-transformed Pichia (Pichia/0), or PBS by gavage, respectively. The expression of TCPTP in macrophages (RAW264.7, BMDMs) and intestinal tissues after IL-35 treatment was detected. After administration of Pichia/IL-35, the mice showed significant improvement in weight loss, bloody stools, and shortened colon. Colon pathology also showed that the inflammatory condition of mice in the Pichia/IL-35 treatment group was alleviated. Notably, Pichia/IL-35 treatment not only increases local M2 macrophages but also decreases the expression of inflammatory cytokine IL-6 in the colon. With Pichia/IL-35 treatment, the proportion of M1 macrophages, Th17, and Th1 cells in mouse MLNs were markedly decreased, while Tregs were significantly increased. In vitro experiments, IL-35 significantly promoted the expression of TCPTP in macrophages stimulated with LPS. Similarly, the mice in the Pichia/IL-35 group also expressed more TCPTP than that of the untreated group and the Pichia/0 group.


Assuntos
Interleucinas , Macrófagos , Camundongos Endogâmicos BALB C , Animais , Masculino , Camundongos , Colite/induzido quimicamente , Colite/metabolismo , Colite Ulcerativa/metabolismo , Colite Ulcerativa/induzido quimicamente , Sulfato de Dextrana , Modelos Animais de Doenças , Interleucinas/metabolismo , Macrófagos/metabolismo , Células RAW 264.7 , Saccharomycetales , Regulação para Cima , Proteína Tirosina Fosfatase não Receptora Tipo 2/metabolismo
5.
Int Immunopharmacol ; 140: 112825, 2024 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-39079347

RESUMO

BACKGROUND: Exosomes derived from endometrial regenerative cells (ERC-Exos) can inherit the immunomodulatory function from ERCs, however, whether ERC-Exos exhibit such effect on inflammatory bowel diseases with mucosal immune dysregulation has not been explored. Insulin-like growth factor-Ⅱ (IGF2) is considered to possess the potential to induce an anti-inflammatory phenotype in immune cells. In this study, the contribution of IGF2 in mediating the protective efficacy of ERC-Exos on colitis was investigated. METHODS: Lentiviral transfection was employed to obtain IGF2-specific knockout ERC-Exos (IGF2-/--ERC-Exos). Experimental colitis mice induced by dextran sulfate sodium (DSS) were divided into the phosphate-buffered saline (untreated), ERC-Exos-treated and IGF2-/--ERC-Exos-treated groups. Colonic histopathological analysis and intestinal barrier function were explored. The infiltration of CD4+ T cells and dendritic cells (DCs) were analyzed by immunofluorescence staining and flow cytometry. The maturation and function of bone marrow-derived dendritic cells (BMDCs) in different exosome administrations were evaluated by flow cytometry, ELISA and the coculture system, respectively. RESULTS: Compared with the untreated group, ERC-Exos treatment significantly attenuated DSS-induced weight loss, bloody stools, shortened colon length, pathological damage, as well as repaired the weakened intestinal mucosal barrier, including promoting the goblet cells retention, restoring the intestinal barrier integrity and enhancing the expression of tight junction proteins, while the protective effect of exosomes was impaired with the knockout of IGF2 in ERC-Exos. Additionally, IGF2-expressing ERC-Exos decreased the proportions of Th1 and Th17, increased the proportions of Treg, as well as attenuated DC infiltration and maturation in mesenteric lymph nodes and lamina propria of the colitis mice. ERC-Exos were also observed to be phagocytosed by BMDCs and IGF2 is responsible for the modulating effect of ERC-Exos on BMDCs in vitro. CONCLUSIONS: Exosomes derived from ERCs can exert a therapeutic effect on experimental colitis with remarkable alleviation of the intestinal barrier damage and the abnormal mucosal immune responses. We emphasized that IGF2 plays a critical role for ERC-Exos mediated immunomodulatory function and protection against colitis.

6.
World J Clin Cases ; 12(21): 4609-4617, 2024 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-39070819

RESUMO

BACKGROUND: Osteoporotic vertebral compression fractures (OVCFs) contribute to back pain and functional limitations in older individuals, with percutaneous vertebroplasty (PVP) emerging as a minimally invasive treatment. However, further height loss post-PVP prompts investigation into contributing factors. AIM: To investigate the factors associated with further height loss following PVP with cement augmentation in OVCF patients. METHODS: A total of 200 OVCF patients who underwent successful PVP between January 2021 and December 2022 were included in this study. "Further height loss" during 1 year of follow-up in OVCF patients with bone edema was defined as a vertical height loss of ≥ 4 mm. The study population was divided into two groups for analysis: The "No Further Height Loss group (n = 179)" and the "Further Height Loss group (n = 21)." RESULTS: In comparing two distinct groups of patients, significant differences existed in bone mineral density (BMD), vertebral compression degree, prevalence of intravertebral cleft (IVF), type of bone cement used, and cement distribution patterns. Results from binary univariate regression analysis revealed that lower BMD, the presence of IVF, cleft distribution of bone cement, and higher vertebral compression degree were all significantly associated with further height loss. Notably, the use of mineralized collagen modified-poly(methyl methacrylate) bone cement was associated with a significant reduction in the risk of further height loss. In multivariate regression analysis, lower BMD and the presence of IVF remained significantly associated with further height loss. CONCLUSION: Further height loss following PVP in OVCF patients is influenced by a complex interplay of factors, especially lower BMD and the presence of IVF. These findings underscore the importance of assessing and managing these factors when addressing height loss following PVP in OVCF patients.

7.
Heliyon ; 10(13): e33855, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-39071614

RESUMO

The electric power industry in China has experienced significant growth in recent years. Despite efforts to improve safety management in the industry, accidents still occur frequently. This study aimed to analyze the personal casualty accidents in the electric power industry from 2012 to 2021. Specific methods used include descriptive analysis, principal component analysis, and Theil index model. The results indicated that fall, electric shock, and collapse were the primary types of accidents, accounting for 59.65 % of all accidents. Accidents were higher in April and August, but lower in February. While the accident rate was relatively low on Mondays, the fatality rate was higher on Mondays, Thursdays, and Fridays. Taking into account accidents, workload, and labor, we found that Ningxia, Hainan, and Guangxi exhibited subpar levels of safety management within the electric power industry. The overall difference in the number of deaths in 31 provinces was significant in 2012 and 2016. It was significantly reduced in 2021. In terms of the proportion of intraregional and interregional differences, there were significant differences in the number of accidents and fatalities between provinces in the Central China and North China regions. This study provides valuable insights for enterprises to formulate accident prevention strategies and for the government to develop relevant policies.

8.
J Oral Rehabil ; 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38873703

RESUMO

OBJECTIVE: This study aimed to investigate whether flow fluid shear stress (FFSS)-mediated signal transduction affects the function of Piezo1 ion channel in chondrocyte and to further explore the role of mechanical overloading in development of temporomandibular joint osteoarthritis (TMJ OA). METHODS: Immunohistochemical staining was used to determine the expression of Piezo1 in TMJ OA tissue collected from rat unilateral anterior crossbite (UAC) models. Chondrocytes harvested from normal adult SD rats were treated with FFSS (0, 4, 8, 12 dyn/cm2) in vitro. Immunofluorescent staining, real-time polymerase chain reaction, western blotting, flow cytometry and phalloidin assay were performed to detect the changes of cellular morphology as well as the expression of Piezo1 and certain pro-inflammatory and degradative factors in chondrocyte. RESULTS: Immunohistochemical analysis revealed that significantly increased Piezo1 expression was associated with UAC stimulation (p < .05). As applied FFSS escalated (4, 8 and 12 dyn/cm2), the expression levels of Piezo1, ADAMTS-5, MMP-13 and Col-X gradually increased, compared with the non-FFSS group (p < .05). Administering Piezo1 ion channel inhibitor to chondrocytes beforehand, it was observed that expression of ADAMTS-5, MMP-13 and Col-X was substantially decreased following FFSS treatment (p < .05) and the effect of cytoskeletal thinning was counteracted. The activated Piezo1 ion channel enhanced intracellular Ca2+ excess in chondrocytes during abnormal mechanical stimulation and the increased intracellular Ca2+ thinned the cytoskeleton of F-actin. CONCLUSIONS: Mechanical overloading activates Piezo1 ion channel to promote pro-inflammation and degradation and to increase Ca2+ concentration in chondrocyte, which may eventually result in TMJ OA.

9.
Adv Sci (Weinh) ; : e2307804, 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38837887

RESUMO

RNA splicing is crucial in the multilayer regulatory networks for gene expression, making functional interactions with DNA- and other RNA-processing machineries in the nucleus. However, these established couplings are all major spliceosome-related; whether the minor spliceosome is involved remains unclear. Here, through affinity purification using Drosophila lysates, an interaction is identified between the minor spliceosomal 65K/RNPC3 and ANKRD11, a cofactor of histone deacetylase 3 (HDAC3). Using a CRISPR/Cas9 system, Deletion strains are constructed and found that both Dm65KΔ/Δ and Dmankrd11Δ/Δ mutants have reduced histone deacetylation at Lys9 of histone H3 (H3K9) and Lys5 of histone H4 (H4K5) in their heads, exhibiting various neural-related defects. The 65K-ANKRD11 interaction is also conserved in human cells, and the HsANKRD11 middle-uncharacterized domain mediates Hs65K association with HDAC3. Cleavage under targets and tagmentation (CUT&Tag) assays revealed that HsANKRD11 is a bridging factor, which facilitates the synergistic common chromatin-binding of HDAC3 and Hs65K. Knockdown (KD) of HsANKRD11 simultaneously decreased their common binding, resulting in reduced deacetylation of nearby H3K9. Ultimately, this study demonstrates that expression changes of many genes caused by HsANKRD11-KD are due to the decreased common chromatin-binding of HDAC3 and Hs65K and subsequently reduced deacetylation of H3K9, illustrating a novel and conserved coupling mechanism that links the histone deacetylation with minor spliceosome for the regulation of gene expression.

10.
Water Res ; 257: 121700, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38705068

RESUMO

Sulfur-based denitrification is a promising technology in treatments of nitrate-contaminated wastewaters. However, due to weak bioavailability and electron-donating capability of elemental sulfur, its sulfur-to-nitrate ratio has long been low, limiting the support for dissimilatory nitrate reduction to ammonium (DNRA) process. Using a long-term sulfur-packed reactor, we demonstrate here for the first time that DNRA in sulfur-based system is not negligible, but rather contributes a remarkable 40.5 %-61.1 % of the total nitrate biotransformation for ammonium production. Through combination of kinetic experiments, electron flow analysis, 16S rRNA amplicon, and microbial network succession, we unveil a cryptic in-situ sulfur disproportionation (SDP) process which significantly facilitates DNRA via enhancing mass transfer and multiplying 86.7-210.9 % of bioavailable electrons. Metagenome assembly and single-copy gene phylogenetic analysis elucidate the abundant genomes, including uc_VadinHA17, PHOS-HE36, JALNZU01, Thiobacillus, and Rubrivivax, harboring complete genes for ammonification. Notably, a unique group of self-SDP-coupled DNRA microorganism was identified. This study unravels a previously concealed fate of DNRA, which highlights the tremendous potential for ammonium recovery and greenhouse gas mitigation. Discovery of a new coupling between nitrogen and sulfur cycles underscores great revision needs of sulfur-driven denitrification technology.


Assuntos
Compostos de Amônio , Nitratos , Nitrogênio , Enxofre , Enxofre/metabolismo , Compostos de Amônio/metabolismo , Nitratos/metabolismo , Nitrogênio/metabolismo , Desnitrificação , Reatores Biológicos , Águas Residuárias , Oxirredução , Filogenia , RNA Ribossômico 16S/genética
11.
Medicine (Baltimore) ; 103(19): e38091, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38728467

RESUMO

To screen immune-related prognostic biomarkers in low-grade glioma (LGG), and reveal the potential regulatory mechanism. The differential expressed genes (DEGs) between alive and dead patients were initially identified, then the key common genes between DEGs and immune-related genes were obtained. Regarding the key DEGs associated with the overall survival (OS), their clinical value was assessed by Kaplan-Meier, RCS, logistic regression, ROC, and decision curve analysis methods. We also assessed the role of immune infiltration on the association between key DEGs and OS. All the analyses were based on the TGCA-LGG data. Finally, we conducted the molecular docking analysis to explore the targeting binding of key DEGs with the therapeutic agents in LGG. Among 146 DEGs, only interleukin-6 (IL-6) was finally screened as an immune-related biomarker. High expression of IL-6 significantly correlated with poor OS time (all P < .05), showing a linear relationship. The combination of IL-6 with IDH1 mutation had the most favorable prediction performance on survival status and they achieved a good clinical net benefit. Next, we found a significant relationship between IL-6 and immune microenvironment score, and the immune microenvironment played a mediating effect on the association of IL-6 with survival (all P < .05). Detailly, IL-6 was positively related to M1 macrophage infiltration abundance and its biomarkers (all P < .05). Finally, we obtained 4 therapeutic agents in LGG targeting IL-6, and their targeting binding relationships were all verified. IL6, as an immune-related biomarker, was associated with the prognosis in LGG, and it can be a therapeutic target in LGG.


Assuntos
Biomarcadores Tumorais , Neoplasias Encefálicas , Glioma , Interleucina-6 , Microambiente Tumoral , Humanos , Interleucina-6/metabolismo , Interleucina-6/genética , Glioma/imunologia , Glioma/genética , Glioma/mortalidade , Microambiente Tumoral/imunologia , Microambiente Tumoral/genética , Prognóstico , Neoplasias Encefálicas/imunologia , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/mortalidade , Biomarcadores Tumorais/genética , Feminino , Estimativa de Kaplan-Meier , Regulação Neoplásica da Expressão Gênica
12.
J Immunother Cancer ; 12(5)2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38782541

RESUMO

BACKGROUND: Accumulating evidence demonstrates that an increased tumor-associated macrophage abundance is often associated with poor prognosis in colorectal cancer (CRC). The mechanism underlying the effect of tumor-derived exosomes on M2 macrophage polarization remains elusive. RESULTS: The novel circular RNA circPOLQ exhibited significantly higher expression in CRC tissues than in paired normal tissues. Higher circPOLQ expression was associated with poorer prognosis in patients with CRC. In vitro and in vivo experiments showed that tumor-derived exosomal circPOLQ did not directly regulate CRC cell development but promoted CRC metastatic nodule formation by enhancing M2 macrophage polarization. circPOLQ activated the interleukin-10/signal transducer and activator of transcription 3 axis by targeting miR-379-3 p to promote M2 macrophage polarization. CONCLUSION: circPOLQ can enter macrophages via CRC cell-derived exosomes and promote CRC metastatic nodule formation by enhancing M2 macrophage polarization. These findings reveal a tumor-derived exosome-mediated tumor-macrophage interaction potentially affecting CRC metastatic nodule formation.


Assuntos
Neoplasias Colorretais , Exossomos , Interleucina-10 , Macrófagos , RNA Circular , Fator de Transcrição STAT3 , Animais , Feminino , Humanos , Masculino , Camundongos , Linhagem Celular Tumoral , Neoplasias Colorretais/patologia , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/genética , Exossomos/metabolismo , Interleucina-10/metabolismo , Ativação de Macrófagos , Macrófagos/metabolismo , RNA Circular/genética , RNA Circular/metabolismo , Transdução de Sinais , Fator de Transcrição STAT3/metabolismo , Macrófagos Associados a Tumor/metabolismo
13.
Mol Ther Nucleic Acids ; 35(2): 102217, 2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38784175

RESUMO

[This retracts the article DOI: 10.1016/j.omtn.2020.05.008.].

14.
BMC Public Health ; 24(1): 1456, 2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38822296

RESUMO

BACKGROUND: As a chronic metabolic disease, diabetes poses a serious threat to human health and has become a major public health problem in China and worldwide. In 2020, 30% of Chinese people (aged ≥ 60 years) reported having diabetes mellitus. Moreover, individuals with diabetes living in rural areas face a significantly higher mortality risk compared to those in urban areas. In this study, we explored the inner experience of self-management behaviors in elderly patients with type 2 diabetes in rural areas to inform targeted interventions. METHODS: A phenomenological research design was used to explore the inner experience of self-management in rural elderly diabetes. Ten elderly diabetic patients were sampled from December 2022 to March 2023 in rural areas of Yangcheng County, Jincheng City, ShanXi Province, China. The seven-step Colaizzi phenomenological was used to analyze the interview data and generate themes. RESULTS: Four themes emerged: "Insufficient self-management cognition", "Negative self-management attitude", "Slack self-management behavior", and "No time for self-management". CONCLUSION: The level of self-management among elderly patients with type 2 diabetes in rural areas is low. Healthcare professionals should develop targeted interventions aimed at enhancing their cognitive levels, modifying their coping styles, and improving their self-management abilities to improve their quality of life.


Assuntos
Diabetes Mellitus Tipo 2 , Pesquisa Qualitativa , População Rural , Autogestão , Humanos , Diabetes Mellitus Tipo 2/terapia , Diabetes Mellitus Tipo 2/psicologia , Idoso , Masculino , Feminino , Autogestão/psicologia , População Rural/estatística & dados numéricos , China/epidemiologia , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais
15.
Cytokine ; 179: 156598, 2024 07.
Artigo em Inglês | MEDLINE | ID: mdl-38583255

RESUMO

BACKGROUND: Allograft rejection remains a major obstacle to long-term graft survival. Although previous studies have demonstrated that IL-37 exhibited significant immunomodulatory effects in various diseases, research on its role in solid organ transplantation has not been fully elucidated. In this study, the therapeutic effect of recombinant human IL-37 (rhIL-37) was evaluated in a mouse cardiac allotransplantation model. METHODS: The C57BL/6 recipients mouse receiving BALB/c donor hearts were treated with rhIL-37. Graft pathological and immunohistology changes, immune cell populations, and cytokine profiles were analyzed on postoperative day (POD) 7. The proliferative capacities of Th1, Th17, and Treg subpopulations were assessed in vitro. Furthermore, the role of the p-mTOR pathway in rhIL-37-induced CD4+ cell inhibition was also elucidated. RESULTS: Compared to untreated groups, treatment of rhIL-37 achieved long-term cardiac allograft survival and effectively alleviated allograft rejection indicated by markedly reduced infiltration of CD4+ and CD11c+ cells and ameliorated graft pathological changes. rhIL-37 displayed significantly less splenic populations of Th1 and Th17 cells, as well as matured dendritic cells. The percentages of Tregs in splenocytes were significantly increased in the therapy group. Furthermore, rhIL-37 markedly decreased the levels of TNF-α and IFN-γ, but increased the level of IL-10 in the recipients. In addition, rhIL-37 inhibited the expression of p-mTOR in CD4+ cells of splenocytes. In vitro, similar to the in vivo experiments, rhIL-37 caused a decrease in the proportion of Th1 and Th17, as well as an increase in the proportion of Treg and a reduction in p-mTOR expression in CD4+ cells. CONCLUSIONS: We demonstrated that rhIL-37 effectively suppress acute rejection and induce long-term allograft acceptance. The results highlight that IL-37 could be novel and promising candidate for prevention of allograft rejection.


Assuntos
Aloenxertos , Rejeição de Enxerto , Transplante de Coração , Interleucina-1 , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Proteínas Recombinantes , Animais , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/prevenção & controle , Humanos , Camundongos , Proteínas Recombinantes/farmacologia , Interleucina-1/metabolismo , Sobrevivência de Enxerto/efeitos dos fármacos , Sobrevivência de Enxerto/imunologia , Células Th1/imunologia , Células Th1/efeitos dos fármacos , Células Th17/imunologia , Células Th17/efeitos dos fármacos , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/efeitos dos fármacos , Masculino , Serina-Treonina Quinases TOR/metabolismo , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos
16.
Heliyon ; 10(8): e29448, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38655317

RESUMO

Background and aim: Solid organ transplantation remains a life-saving therapeutic option for patients with end-stage organ dysfunction. Acute cellular rejection (ACR), dominated by dendritic cells (DCs) and CD4+ T cells, is a major cause of post-transplant mortality. Inhibiting DC maturation and directing the differentiation of CD4+ T cells toward immunosuppression are keys to inhibiting ACR. We propose that oxymatrine (OMT), a quinolizidine alkaloid, either alone or in combination with rapamycin (RAPA), attenuates ACR by inhibiting the mTOR-HIF-1α pathway. Methods: Graft damage was assessed using haematoxylin and eosin staining. Intragraft CD11c+ and CD4+ cell infiltrations were detected using immunohistochemical staining. The proportions of mature DCs, T helper (Th) 1, Th17, and Treg cells in the spleen; donor-specific antibody (DSA) secretion in the serum; mTOR-HIF-1α expression in the grafts; and CD4+ cells and bone marrow-derived DCs (BMDCs) were evaluated using flow cytometry. Results: OMT, either alone or in combination with RAPA, significantly alleviated pathological damage; decreased CD4+ and CD11c+ cell infiltration in cardiac allografts; reduced the proportion of mature DCs, Th1 and Th17 cells; increased the proportion of Tregs in recipient spleens; downregulated DSA production; and inhibited mTOR and HIF-1α expression in the grafts. OMT suppresses mTOR and HIF-1α expression in BMDCs and CD4+ T cells in vitro. Conclusions: Our study suggests that OMT-based therapy can significantly attenuate acute cardiac allograft rejection by inhibiting DC maturation and CD4+ T cell responses. This process may be related to the inhibition of the mTOR-HIF-1α signaling pathway by OMT.

17.
Chem Biodivers ; 21(6): e202302037, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38546704

RESUMO

Tinospora sinensis (T. sinensis), whose Tibetan name is "Lezhe", as a traditional medicine, is widely distributed in China, India and Sri Lanka. It is used for the treatment of rheumatic arthralgia, sciatica, lumbar muscle strain and bruises. Research over the previous decades indicated that T. sinensis mainly contains terpenes, lignans, alkaloids, phenol glycosides and other chemical components. A wide range of pharmacologic activities such as anti-inflammatory, analgesic, immunosuppressive, anti-aging, anti-radiation, anti-leishmania and liver protection have been reported. However, the scholar's research on the pharmacodynamic material basis of T. sinensis is relatively weak. Data regarding many aspects such as links between the traditional uses and bioactivities, pharmacokinetics, and quality control standard of active compositions is still limited and need more attention. This review reports a total of 241 compounds, the ethnopharmacology and clinical application of T. sinensis, covering the literature which were searched by multiple databases including Web of Science, PubMed, Google Scholar, Science Direct, CNKI and other literature sources from 1996 to date, with a view to provide a systematic and insightful reference and lays a foundation and inspiration for the application and further in-depth research of T. sinensis resources.


Assuntos
Compostos Fitoquímicos , Tinospora , Tinospora/química , Humanos , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/química , Compostos Fitoquímicos/isolamento & purificação , Medicina Tradicional , Animais , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Extratos Vegetais/isolamento & purificação
18.
J Int Med Res ; 52(3): 3000605241233418, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38548472

RESUMO

OBJECTIVES: Despite being an important research topic in oral biomaterials, few studies have demonstrated the differences between poly(d,l-lactide-co-glycolide)/hydroxyapatite (PLGA/HA) and poly(d,l-lactic acid)/hydroxyapatite (PDLLA/HA). In this study, PLGA/HA and PDLLA/HA scaffolds were prepared using three-dimensional (3D) printing technology and implanted into radius defects in rabbits to assess their effects on bone regeneration. METHODS: In this study, 6 mm × 4 mm bone defects were generated in the bilateral radii of rabbits. 3D-printed PLGA/HA and PDLLA/HA scaffolds were implanted into the defects. X-ray imaging, micro-computed tomography, and hematoxylin-eosin staining were performed to observe the degradation of the materials, the presence of new bone, and bone remodeling in the bone defect area. RESULTS: The PLGA/HA scaffolds displayed complete degradation at 20 weeks, whereas PDLLA/HA scaffolds exhibited incomplete degradation. Active osteoblasts were detected in both groups. The formation of new bone, bone marrow cavity reconstruction, and cortical bone remodeling were better in the PLGA/HA group than in the PDLLA/HA group. CONCLUSIONS: PLGA/HA scaffolds performed better than PDLLA/HA scaffolds in repairing bone defects, making the former scaffolds more suitable as bone substitutes at the same high molecular weight.


Assuntos
Ácido Poliglicólico , Rádio (Anatomia) , Animais , Coelhos , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Rádio (Anatomia)/diagnóstico por imagem , Rádio (Anatomia)/cirurgia , Ácido Láctico , Microtomografia por Raio-X , Durapatita , Impressão Tridimensional , Alicerces Teciduais
19.
Small ; : e2401143, 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38534196

RESUMO

The regulation of the crystal structure of oxygen evolution cocatalyst (OEC) is a promising strategy for enhancing the photoelectrochemical efficiency of photoanodes. However, the prevailing regulating approach typically requires a multistep procedure, presenting a significant challenge for maintaining the structural integrity and performance of the photoanode. Herein, FeOOH with a local disordered structure is directly grown on a CdIn2S4 (CIS) photoanode via a simple and mild sonochemical approach. By modulating the localized supersaturation of Ni ions, ultrasonic cavitation induces Ni ions to participate in the nucleation and growth of FeOOH clusters to cause local disorder of FeOOH. Consequently, the local disordered FeOOH facilitates the exposure of additional active sites, boosting OER kinetics and extending charge carrier lifetimes. Finally, the optimal photoanode reaches 4.52 mA cm-2 at 1.23 VRHE, and the onset potential shifts negatively by 330 mV, exhibiting excellent performance compared with that of other metal sulfide-based photoelectrodes reported thus far. This work provides a mild and controllable sonochemical method for regulating the phase structure of OECs to construct high-performance photoanodes.

20.
Orthop Surg ; 16(4): 953-964, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38389204

RESUMO

OBJECTIVE: Surgical treatment with internal fixation, specifically percutaneous fixation with three cannulated compression screws (CCSs), is the preferred choice for young and middle-aged patients. The mechanical advantage of the optimal spatial configuration with three screws provides maximum dispersion and cortical support. We suspect that the spatial proportion of the oblique triangle configuration (OTC) in the cross-section of the femoral neck isthmus (FNI) may significantly improve shear and fatigue resistance of the fixed structure, thereby stabilizing the internal fixation system in femoral neck fracture (FNF). This study aims to explore the mechanical features of OTC and provide a mechanical basis for its clinical application. METHODS: Twenty Sawbone femurs were prepared as Pauwels type III FNF models and divided equally into two fixation groups: OTC and inverted equilateral triangle configuration (IETC). Three 7.3 mm diameter cannulated compression screws (CCSs) were used for fixation. The specimens of FNF after screw internal fixation were subjected to static loading and cyclic loading tests, respectively, with five specimens for each test. Axial stiffness, 5 mm failure load, ultimate load, shear displacement, and frontal rotational angle of two fragments were evaluated. In the cyclic loading test, the load sizes were 700 N, 1400 N, and 2100 N, respectively, and the fracture end displacement was recorded. Results were presented as means ± SD. Data with normal distributions were compared by the Student's t test. RESULTS: In the static loading test, the axial stiffness, ultimate load, shear displacement, and frontal rotational angle of two fragments were (738.64 vs. 620.74) N/mm, (2957.61 vs. 2643.06) N, (4.67 vs. 5.39) mm, and (4.01 vs. 5.52)° (p < 0.05), respectively. Comparison between the femoral head displacement after 10,000 cycles of 700N cyclic loading and total displacement after 20,000 cycles of 700-1400N cyclic loading showed the OTC group was less than the IETC group (p < 0.05). A comparison of femoral head displacement after 10,000 cycles of 1400N and 2100N cycles and total displacement after 30,000 cycles of 700-2100N cycles showed the OTC group was less than another group, but the difference was not significant (p > 0.05). CONCLUSION: When three CCSs are inserted in parallel to fix FNF, the OTC of three screws has obvious biomechanical advantages, especially in shear resistance and early postoperative weight-bearing, which provides a mechanical basis for clinical selection of ideal spatial configuration for unstable FNF.


Assuntos
Fraturas do Colo Femoral , Colo do Fêmur , Pessoa de Meia-Idade , Humanos , Colo do Fêmur/cirurgia , Fenômenos Biomecânicos , Fraturas do Colo Femoral/cirurgia , Parafusos Ósseos , Fêmur , Fixação Interna de Fraturas/métodos
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