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1.
Artigo em Inglês | MEDLINE | ID: mdl-35044489

RESUMO

The CD169+ macrophages in lymph nodes are implicated in cytotoxic T lymphocyte (CTL) activation and are associated with improved prognosis in several malignancies. Here, we investigated the significance of CD169+ macrophages in oral squamous cell carcinoma (OSCC). Further, we tested the anti-tumor effects of naringenin, which has been previously shown to activate CD169+ macrophages, in a murine OSCC model. Immunohistochemical analysis for CD169 and CD8 was performed on lymph node and primary tumor specimens from 89 patients with OSCC. We also evaluated the effects of naringenin on two murine OSCC models. Increased CD169+ macrophage counts in the regional lymph nodes correlated with favorable prognosis and CD8+ cell counts within tumor sites. Additionally, naringenin suppressed tumor growth in two murine OSCC models. The mRNA levels of CD169, interleukin (IL)-12, and C-X-C motif chemokine ligand 10 (CXCL10) in lymph nodes and CTL infiltration in tumors significantly increased following naringenin administration in tumor-bearing mice. These results suggest that CD169+ macrophages in lymph nodes are involved in T cell-mediated anti-tumor immunity and could be a prognostic marker for patients with OSCC. Moreover, naringenin is a new potential agent for CD169+ macrophage activation in OSCC treatment.

2.
Nanoscale ; 2022 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-35014657

RESUMO

Owing to their excellent sensitivity, stretchability, flexibility and conductivity, polymeric nanocomposites with conductive fillers have shown promise for a wide range of applications in bioelectronics and wearable devices. Herein, we report on the development of a flexible and biocompatible polymeric nanocomposite comprising ultra-long Ag-Au core-sheath nanowires (Au@AgNWs) dispersed in elastomeric media to fabricate a high-resolution wearable temperature sensor. Ultra-long AgNWs with an aspect ratio of about 1500 were synthesized using a Ca2+ ion-mediated facile one-pot polyol process. To enhance the biocompatibility and anti-oxidative property of the AgNWs, a 10-20 nm gold (Au) layer was conformably deposited without affecting the original nanowire morphology. The core-sheath structure of Au@AgNWs was characterized using HRTEM and EDS elemental mapping while the biocompatibility and anti-oxidative properties were tested using hydrogen peroxide (H2O2) etching in solution phase. Finally, the fabricated nanowires were used to prepare the Au@AgNW-poly-ethylene glycol (PEG)-polyurethane (PU)-based nanocomposite ink which can be printed on interdigitated electrodes to fabricate a thermoresistive temperature sensor with negative temperature coefficient (NTC) of resistance and quick response time (<100 s). The Au@AgNW-PEG-PU nanocomposite was characterized in detail and a novel temperature sensing mechanism based on controlling the internanowire distance of the PEG coated Au@AgNWs percolation by means of capillarity force among the nanowires as a result of the glass transition temperature of thermosensitive PEG was demonstrated. The proposed printable temperature sensor is flexible and biocompatible and shows promise for a range of wearable applications.

3.
Int J Cardiol Heart Vasc ; 38: 100938, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34977329

RESUMO

Purpose: This study evaluated the diagnostic values of the extent of lung injury manifested in non-contrast enhanced CT (NCCT) images, the inflammatory and immunological biomarkers C-reactive protein (CRP) and lymphocyte for detecting acute cardiac injury (ACI) in patients with COVID-19. The correlations between the NCCT-derived parameters and arterial blood oxygen level were also investigated. Methods: NCCT lung images and blood tests were obtained in 143 patients with COVID-19 in approximately two weeks after symptom onset, and arterial blood gas measurement was also acquired in 113 (79%) patients. The diagnostic values of normal, moderately and severely abnormal lung parenchyma volume relative to the whole lungs (RVNP, RVMAP, RVSAP, respectively) measured from NCCT images for detecting the heart injury confirmed with high-sensitivity troponin I assay was determined. Results: RVNP, RVMAP and RVSAP exhibited similar accuracy for detecting ACI in COVID-19 patients. RVNP was significantly lower while both RVMAP and RVSAP were significantly higher in the patients with ACI. All of the NCCT-derived parameters exhibited poor linear and non-linear correlations with PaO2 and SaO2. The patients with ACI had a significantly higher CRP level but a lower lymphocyte level compared to the patients without ACI. Combining one of these two biomarkers with any of the three NCCT-derived parameter further improved the accuracy for predicting ACI in patients with COVID-19. Conclusion: The NCCT-delineated normal and abnormal lung parenchmyma tissues were statistically significant predictors of ACI in patients with COVID-19, but both exhibited poor correlations with the arterial blood oxygen level. The incremental diagnostic values of lymphocyte and CRP suggested viral infection and inflammation were closely related to the heart injury during the acute stage of COVID-19.

4.
Medicine (Baltimore) ; 100(44): e27524, 2021 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-34871214

RESUMO

BACKGROUND: Lung cancer is the leading cause of death among cancer patients worldwide. Close to 85% of lung cancer pathology types are nonsmall cell lung cancer (NSCLC). With advances in medicine, the survival rate of early-stage NSCLC has improved. Nevertheless, about 70% of patients are diagnosed at an advanced stage, and chemotherapy is the primary treatment option. Chemotherapy causes toxic side effects such as bone marrow suppression, gastrointestinal reactions, and damage to vital organs, which are difficult for patients to tolerate. Many published literatures have reported that Shenmai injection (SMI) combined with platinum-containing first-line chemotherapy regimen for NSCLC can improve the recent efficacy, reduce toxic side effects and improve the quality of life. However, most of the studies were small samples and lacked persuasive power, while controversies existed among individual studies. Therefore, this study used meta-analysis to further evaluate the effects of SMI combined with platinum-containing first-line chemotherapy on the quality of life, immune function and prognosis of patients with NSCLC. METHODS: Wanfang, Chinese Biomedical Literature Database, Chinese National Knowledge Infrastructure, the Chongqing VIP Chinese Science and Technology Periodical Database, PubMed, Embase, and Web of Science databases were searched. The search was scheduled from the establishment of the database to September 2021. All randomized controlled trials comparing SMI in combination with platinum-containing first-line chemotherapy to platinum-containing first-line chemotherapy alone for the treatment of NSCLC were searched and evaluated for inclusion. Two investigators independently performed study selection, data extraction and synthesis. The Cochrane Risk of Bias tool was used to assess the risk of bias in the randomized controlled trials. Stata 16.0 software was used for meta-analysis. RESULTS: The results of this meta-analysis will be submitted to a peer-reviewed journal for publication. CONCLUSION: This study comprehensively evaluated the effects of SMI combined with platinum-containing first-line chemotherapy on quality of life, immune function and prognosis in patients with NSCLC to provide an evidence-based basis for clinical practice. ETHICS AND DISSEMINATION: The private information from individuals will not be published. This systematic review should also not damage participants' rights. Ethical approval was not available. The results may be published in a peer-reviewed journal or disseminated in relevant conferences.OSF Registration number: DOI 10.17605/OSF.IO/AMKDC.

5.
Chin J Integr Med ; 2021 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-34874516

RESUMO

OBJECTIVE: To investigate the protective effect of Chinese herbal formula Huangqin Decoction (HQD) on ulcerative colitis mouse model induced by dextran sulphate sodium (DSS) and human intestinal epithelial cell injury induced by tumour necrosis factor-α (TNF-α). METHODS: In vivo, 30 male C57BL/6 mice were divided into 5 groups using a random number table (n=6 per group), including control, DSS, 5-aminosalicylic acid (5-ASA), HQD low- (HQD-L) and high-dose (HQD-H) groups. The colitis mouse model was established by 3% (w/v) DSS water for 5 days. Meanwhile, mice in the HQD-L, HQD-H and 5-ASA groups were administrated with 100, 200 mg/kg HQD or 100 mg/kg 5-ASA, respectively, once daily by gavage. After 9 days of administration, the body weight, disease activity index (DAI) score and colon length of mice were measured, the pathological changes of colons were analyzed by hematoxylin-eosin staining (HE) staining, and the levels of serum interleukin (IL)-6, IL-1ß and TNF-α were measured by enzyme linked immunosorbent assay. In vitro, the human colon epithelial normal cells (FHC cells) were exposed to HQD (0.6 mg/mL) for 12 h and then treated with TNF-α (10 ng/mL) for 24 h. The tight junction (TJ) protein expression levels of Claudin-4 and Occludin, and the protein phosphorylation levels of p65 and inhibitor of nuclear factor kappaB (NF-κB)-α (IκBα) were measured by Western blot. RESULTS: In vivo, compared with the DSS group, HQD-H treatment attenuated the weight loss and reduced DAI score of mice on the 8th day (P<0.05). Moreover, HQD-H treatment ameliorated the colon shortening in the DSS-induced colitis mice (P<0.05). HE staining showed HQD attenuated the pathological changes of colitis mice, and the histological scores of HQD-H and 5-ASA groups were significantly decreased compared with the DSS group (P<0.05). Meanwhile, HQD-H and 5-ASA significantly decreased the serum IL-1ß, IL-6 and TNF-α levels of mice (P<0.05). In vitro experiments showed that HQD up-regulated Occludin and Claudin-4 protein expressions and inhibited p-p65 and p-IκBα levels in FHC cells compared with the TNF-α group (P<0.05). CONCLUSION: HQD significantly relieved the symptoms in DSS-induced colitis mice by inhibiting pro-inflammatory cytokines expression and maintained the homeostasis of TJ protein in FHC cells by suppressing TNF-α-induced NF-κB activation.

7.
Micromachines (Basel) ; 12(11)2021 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-34832706

RESUMO

The tibia of New Zealand White rabbits was used as a model of critical bone defects to investigate a new design of composite scaffold for bone defects composed of dual materials. The all-in-one design of a titanium alloy (Ti-6Al-4V) scaffold comprised the structure of a bone plate and gradient porosity cage. Hydroxyapatite (HAp), a biodegradable material, was encapsulated in the center of the scaffold. The gradient pore structure was designed with 70%-65%-60%-55%-50% porosity, since the stresses could be distributed more uniformly when the all-in-one scaffold was placed on the bone contact surface. By covering the center of the scaffold with a low strength of HAp to contact the relatively low strength of bone marrow tissues, the excessive stiffness of the Ti-6Al-4V can be effectively reduced and further diminish the incidence of the stress shielding effect. The simulation results show that the optimized composite scaffold for the 3D model of tibia had a maximum stress value of 27.862 MPa and a maximum strain of 0.065%. The scaffold prepared by selective laser melting was annealed and found that the Young's coefficient increased from 126.44 GPa to 131.46 GPa, the hardness increased from 3.9 GPa to 4.12 GPa, and the strain decreased from 2.27% to 1.13%. The result demonstrates that the removal of residual stress can lead to a more stable structural strength, which can be used as a reference for the design of future clinical tibial defect repair scaffolds.

9.
Artigo em Inglês | MEDLINE | ID: mdl-34655303

RESUMO

Tumor-associated macrophages (TAMs), especially the M2-like phenotype, promote tumor progression, making them candidate targets for anti-tumor therapy. We previously discovered a cyclic sulfur compound, Onionin A (ONA), which suppresses tumor progression by inhibiting the M2-polarization of TAMs. In the present study, we sought to find new candidate compounds possessing a stronger effect compared to ONA by exploring compounds with structures similar to those of ONA among several cyclic sulfur compounds. A total of 81 cyclic sulfur compounds were screened, and their effects on macrophage polarization toward an M2-like phenotype were tested using human monocyte-derived macrophages (HMDMs). The anti-tumor effects of the identified candidate compounds were examined in a tumor-bearing mouse model. Three candidate compounds inhibited both IL-10- and tumor culture supernatant (TCS)-induced M2-polarization of HMDMs. These compounds also suppressed STAT3 activation in HMDMs stimulated by IL-10 and TCS, whereas these compounds had no effect on STAT3 activation in tumor cells. Furthermore, these compounds inhibited tumor cell proliferation under co-culture conditions with HMDMs, indicating that the three candidate compounds suppress tumor proliferation by regulating cell-cell interactions between tumor cells and macrophages. In addition, two of these candidate compounds had inhibitory effects on tumor growth and lung metastasis in the LM8 tumor-bearing mouse model. Our study identified new candidate cyclic sulfur compounds for anti-tumor therapy targeting the M2-polarization of TAMs.

10.
Pharmaceutics ; 13(9)2021 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-34575492

RESUMO

The objective of this study aimed to develop biodegradable calcium alginate microspheres carrying doxorubicin (Dox) at the micrometer-scale for sustained release and the capacity of pH regulatory for transarterial chemoembolization. Ultrasonic atomization and CaCl2 cross-linking technologies were used to prepare the microspheres. A 4-by-5 experiment was first designed to identify imperative parameters. The concentration of CaCl2 and the flow rate of the pump were found to be critical to generate microspheres with a constant volume median diameter (~39 µm) across five groups with different alginate: NaHCO3 ratios using each corresponding flow rate. In each group, the encapsulation efficiency was positively correlated to the Dox-loading %. Fourier-transform infrared spectroscopy showed that NaHCO3 and Dox were step-by-step incorporated into the calcium alginate microspheres successfully. Microspheres containing alginate: NaHCO3 = 1 exhibited rough and porous surfaces, high Young's modulus, and hardness. In each group with the same alginate: NaHCO3 ratio, the swelling rates of microspheres were higher in PBS containing 10% FBS compared to those in PBS alone. Microspheres with relatively high NaHCO3 concentrations in PBS containing 10% FBS maintained better physiological pH and higher accumulated Dox release ratios. In two distinct hepatocellular carcinoma-derived cell lines, treatments with microspheres carrying Dox demonstrated that the cell viabilities decreased in groups with relatively high NaHCO3 ratios in time- and dose-dependent manners. Our results suggested that biodegradable alginate microspheres containing relatively high NaHCO3 concentrations improved the cytotoxicity effects in vitro.

11.
Diagnostics (Basel) ; 11(9)2021 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-34573941

RESUMO

Due to the fact that previous studies have rarely investigated the recognition rate discrepancy and pathology data error when applied to different databases, the purpose of this study is to investigate the improvement of recognition rate via deep learning-based liver lesion segmentation with the incorporation of hospital data. The recognition model used in this study is H-DenseUNet, which is applied to the segmentation of the liver and lesions, and a mixture of 2D/3D Hybrid-DenseUNet is used to reduce the recognition time and system memory requirements. Differences in recognition results were determined by comparing the training files of the standard LiTS competition data set with the training set after mixing in an additional 30 patients. The average error value of 9.6% was obtained by comparing the data discrepancy between the actual pathology data and the pathology data after the analysis of the identified images imported from Kaohsiung Chang Gung Memorial Hospital. The average error rate of the recognition output after mixing the LiTS database with hospital data for training was 1%. In the recognition part, the Dice coefficient was 0.52 after training 50 epochs using the standard LiTS database, while the Dice coefficient was increased to 0.61 after adding 30 hospital data to the training. After importing 3D Slice and ITK-Snap software, a 3D image of the lesion and liver segmentation can be developed. It is hoped that this method could be used to stimulate more research in addition to the general public standard database in the future, as well as to study the applicability of hospital data and improve the generality of the database.

13.
Front Psychol ; 12: 752303, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34589038

RESUMO

Along with the rapid development of electronic technology, the appeal of information technology to students and teachers in domestic and international information education has become universal. Education-related departments aim to positively cultivate the professional information knowledge and skills of teachers. The use of information technology in instruction allows students to enhance their creativity and learning motivation. A total of 232 college students from Fujian Province participated in the experimental research. The results show the following: (1) the application of information technology to e-book teaching could enhance a sense of achievement of students in self-directed learning, and students could answer test questions in a confidential and relaxed manner; (2) the application of information technology to e-book teaching activates teaching flexibility, and many teaching models, such as teaching by wandering around, interactive teaching, and blended teaching, are therefore derived to enhance the richness of teaching; (3) the application of information technology to e-book teaching bridges the distance between instructors and students and leads to a deeper understanding of learning conditions of students, expanding the possibilities for content planning and teaching models. The results give rise to suggestions enhancing enjoyment in learning and promoting higher motivation and more effective teaching.

14.
Acta Biomater ; 135: 100-112, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34389483

RESUMO

Chronic wounds remain a worldwide clinical challenge, and bioactive materials that can promote skin regeneration are required. Self-assembling peptide (SAP) hydrogels have shown great potential in tissue repair, but their regenerative efficacy and possible mechanism in chronic wound healing are unclear. Here, we report an SAP (KGH) that enhances extracellular matrix (ECM) remodeling and angiogenesis, thereby promoting chronic wound healing in diabetic mice. In vivo, the KGH hydrogel was retained in wounds up to 7 days after injection, and it was effective in speeding up wound closure by ∼20% compared to the control groups and enhancing angiogenesis (e.g., VEGFA, CD31+ capillaries), cell proliferation (e.g., PCNA+ cells), formation of granulation tissue (e.g., α-SMA), and ECM deposition/remodeling (e.g., collagen I, fibronectin). In vitro, the KGH hydrogel created a 3D microenvironment for skin cells, maintained the sustained growth of cell spheroids, and increased the secretion of ECM proteins (e.g., laminin) and growth factors (e.g., PDGFB, VEGFA, and TGF-ß) in skin keratinocytes compared to the conventional 2D culture. Mechanistically, the KGH hydrogel might promote wound tissue regeneration by activating the Rho/ROCK and TGF-ß/MEK/MAPK pathways. As a type of designed material, SAP can be further re-engineered with biological motifs, therapeutic reagents, or stem cells to enhance skin regeneration. This study highlights that SAP hydrogels are a promising material platform for advanced chronic wound healing and might have translational potential in future clinical applications. STATEMENT OF SIGNIFICANCE: Chronic wounds are a common and serious health issue worldwide, and bioactive dressing materials are required to address this issue. SAP hydrogels have shown certain tissue repair potential, but their regenerative efficacy and underlying mechanism in chronic wound healing remain elusive. Herein, we report that SAP hydrogels create a native 3D microenvironment that can remarkably stimulate angiogenesis and ECM remodeling in diabetic wounds. Mechanistically, the SAP hydrogel promoted ECM proteins and GFs secretion in skin cells through the activation of the Rho/ROCK and TGF-ß/MEK/MAPK pathways. Additionally, SAP can be readily engineered with various bioactive motifs or therapeutic drugs/cells. This work highlights SAP hydrogels as a promising biomaterial platform for chronic wound healing and the regeneration of many other tissues.


Assuntos
Diabetes Mellitus Experimental , Nanofibras , Animais , Hidrogéis/farmacologia , Camundongos , Peptídeos/farmacologia , Cicatrização
15.
Cell Oncol (Dordr) ; 44(5): 1133-1150, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34339014

RESUMO

PURPOSE: Urinary bladder urothelial carcinoma (UBUC) is a common malignant disease, and its high recurrence rates impose a heavy clinical burden. The objective of this study was to identify signaling pathways downstream of epithelial membrane protein 2 (EMP2), which induces cytostasis and apoptosis in UBUC. METHODS: A series of in vitro and in vivo assays using different UBUC-derived cell lines and mouse xenograft models were performed, respectively. In addition, primary UBUC specimens were evaluated by immunohistochemistry. RESULTS: Exogenous expression of EMP2 in J82 UBUC cells significantly decreased DNA replication and altered the expression levels of several TGFß signaling-related proteins. EMP2 knockdown in BFTC905 UBUC cells resulted in opposite effects. EMP2-dysregulated cell cycle progression was found to be mediated by the TGFß/TGFBR1/SP1 family member SMAD. EMP2 or purinergic receptor P2X7 (P2RX7) gene expression upregulation induced apoptosis via both intrinsic and extrinsic pathways. In 242 UBUC patient samples, P2RX7 protein levels were found to be significantly and positively correlated with EMP2 protein levels. Low P2RX7 levels conferred poor disease-specific and metastasis-free survival rates, and significantly decreased apoptotic cell rates. EMP2 was found to physically interact with P2RX7. In the presence of a P2RX7 agonist, BzATP, overexpression of both EMP2 and P2RX7 significantly increased apoptotic cell rates compared to overexpression of EMP2 or P2RX7 alone. CONCLUSIONS: EMP2 induces cytostasis via the TGFß/SMAD/SP1 axis and recruits P2RX7 to enhance apoptosis in UBUC. Our data provide new insights that may be employed for the design of UBUC targeting therapies.

16.
Artigo em Inglês | MEDLINE | ID: mdl-34339842

RESUMO

Wild castor grows in the high-altitude tropical desert of the African Plateau, a region known for high ultraviolet radiation, strong light, and extremely dry condition. To investigate the potential genetic basis of adaptation to both highland and tropical deserts, we generated a chromosome-level genome sequence assembly of the wild castor accession WT05, with a genome size of 316 Mb, a scaffold N50 of 31.93 Mb, and a contig N50 of 8.96 Mb, respectively. Compared with cultivated castor and other Euphorbiaceae species, the wild castor exhibits positive selection and gene family expansion for genes involved in DNA repair, photosynthesis, and abiotic stress responses. Genetic variations associated with positive selection were identified in several key genes, such as LIG1, DDB2, and RECG1, involved in nucleotide excision repair. Moreover, a study of genomic diversity among wild and cultivated accessions revealed genomic regions containing selection signatures associated with the adaptation to extreme environments. The identification of the genes and alleles with selection signatures provides insights into the genetic mechanisms underlying the adaptation of wild castor to the high-altitude tropical desert and would facilitate direct improvement of modern castor varieties.

17.
Materials (Basel) ; 14(15)2021 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-34361427

RESUMO

Polymethylsilsesquioxane (PMSQ) has become a kind of widely studied filler used in the electronic circuit board substrates due to its organic-inorganic hybrid structure, low dielectric constant, and good thermal stability, among other factors. Herein, the PMSQ microspheres were prepared by a two-step acid-base-catalyzed sol-gel method; the influences of reaction conditions including the ratio of water/methyltrimethoxysilane (MTMS), reaction temperature, concentration of the catalyst, and stirring time were systematically investigated; and the optimized reaction condition was then obtained towards a narrow particle size distribution and good sphericity. The microstructure of PMSQ microspheres was analyzed by the infrared spectrum and X-ray diffraction (XRD), which indicated that the as-prepared PMSQ had a ladder-dominant structure. The thermogravimetric analysis (TGA) demonstrated an excellent thermal stability of as-prepared PMSQ microspheres. More specifically, the dielectric constants at high frequency (1~20 GHz) of as-prepared PMSQ microspheres were measured to be about 3.7, which turned out a lower dielectric constant compared to SiO2 powder (≈4.0). This study paves the way to further improve the performance of the electronic circuit board substrates for the application of high-frequency electronic packaging.

18.
Mol Med Rep ; 24(4)2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34368880

RESUMO

Diabetic gastroparesis (DGP), also known as delayed gastric emptying, is a common complication of diabetes mellitus. There are numerous clinical symptoms associated with DGP, as well as high treatment costs and markedly reduced patient quality of life. However, the pathogenesis of DGP is not clear, thus effective treatment methods are yet to be established. In the present study, a DGP rat model was established in Sprague­Dawley rats by the intraperitoneal injection of streptozotocin (STZ). DGP model rats were treated with different doses of atractylenolide­1 to detect alterations in gastrointestinal function, including gastroparesis, gastric emptying, gastric motility, gastric peristalsis and gastric blood flow. Compared with the DGP group, atractylenolide­1 treatment significantly reduced glycaemia and the level of glycated hemoglobin, as well as restoring gastrointestinal function. Gastroparesis, gastric emptying, gastric motility, gastric peristalsis and gastric blood flow were significantly impaired in the STZ­induced group compared with the vehicle control group. Moreover, the STZ­induced group displayed downregulated expression levels of the DGP indicator KIT proto­oncogene, receptor tyrosine kinase (c­kit), as investigated by immunohistochemistry, and stem cell factor (SCF) protein, as assessed using ELISA, significantly enhanced rat interstitial cells of Cajal (ICC) apoptosis, and significantly altered levels of oxidative stress­related markers (malondialdehyde and superoxide dismutase) in the serum and gastric tissues compared with the vehicle control group. By contrast, treatment with atractylenolide­1 significantly counteracted the effects of DGP on peristalsis, inhibited apoptosis and suppressed oxidative stress by regulating the expression of heme oxygenase 1 in STZ­induced DGP model rats. Further research indicated that atractylenolide­1 regulated oxidative stress reactions and improved gastric function by activating the SCF/c­kit signaling pathway. Collectively, the results of the present study suggested that atractylenolide­1 promoted ICC survival and preserved the structure of the gastric tissue network in a DGP rat model via the SCF/c­kit signaling pathway, providing novel insights for the treatment of DGP.

19.
Artigo em Inglês | MEDLINE | ID: mdl-34360309

RESUMO

Maneuvering a wheelchair is an important necessity for the everyday life and social activities of people with a range of physical disabilities. However, in real life, wheelchair users face several common challenges: articulate steering, spatial relationships, and negotiating obstacles. Therefore, our research group has developed a head-mounted display (HMD)-based intuitive virtual reality (VR) stimulator for wheelchair propulsion. The aim of this study was to investigate the feasibility and efficacy of this VR stimulator for wheelchair propulsion performance. Twenty manual wheelchair users (16 men and 4 women) with spinal cord injuries ranging from T8 to L2 participated in this study. The differences in wheelchair propulsion kinematics between immersive and non-immersive VR environments were assessed using a 3D motion analysis system. Subjective data of the HMD-based intuitive VR stimulator were collected with a Presence Questionnaire and individual semi-structured interview at the end of the trial. Results indicated that propulsion performance was very similar in terms of start angle (p = 0.34), end angle (p = 0.46), stroke angle (p = 0.76), and shoulder movement (p = 0.66) between immersive and non-immersive VR environments. In the VR episode featuring an uphill journey, an increase in propulsion speed (p < 0.01) and cadence (p < 0.01) were found, as well as a greater trunk forward inclination (p = 0.01). Qualitative interviews showed that this VR simulator made an attractive, novel impression and therefore demonstrated the potential as a tool for stimulating training motivation. This HMD-based intuitive VR stimulator can be an effective resource to enhance wheelchair maneuverability experiences.


Assuntos
Traumatismos da Medula Espinal , Realidade Virtual , Cadeiras de Rodas , Fenômenos Biomecânicos , Feminino , Humanos , Masculino
20.
Cancer Res ; 81(17): 4545-4559, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34210751

RESUMO

Blood levels of acute-phase protein α1-acid glycoprotein (AGP, orosmucoid) increase in patients with cancer. Although AGP is produced from hepatocytes following stimulation by immune cell-derived cytokines under conditions of inflammation and tumorigenesis, the functions of AGP in tumorigenesis and tumor progression remain unknown. In the present study, we revealed that AGP contributes directly to tumor development by induction of programmed death ligand 1 (PD-L1) expression and IL6 production in macrophages. Stimulation of AGP induced PD-L1 expression in both human monocyte-derived macrophages through STAT1 activation, whereas AGP had no direct effect on PD-L1 expression in tumor cells. AGP also induced IL6 production from macrophages, which stimulated proliferation in tumor cells by IL6R-mediated activation of STAT3. Furthermore, administration of AGP to AGP KO mice phenocopied effects of tumor-associated macrophages (TAM) on tumor progression. AGP decreased IFNγ secretion from T cells and enhanced STAT3 activation in subcutaneous tumor tissues. In addition, AGP regulated PD-L1 expression and IL6 production in macrophages by binding with CD14, a coreceptor for Toll-like receptor 4 (TLR4), and inducing TLR4 signaling. These results provide the first evidence that AGP is directly involved in tumorigenesis by interacting with TAMs and that AGP might be a target molecule for anticancer therapy. SIGNIFICANCE: AGP-mediated suppression of antitumor immunity contributes to tumor progression by inducing PD-L1 expression and IL6 production in TAMs.

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