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1.
Bioact Mater ; 8: 355-367, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34541406

RESUMO

Peripheral nerve regeneration and functional recovery remain a major clinical challenge. Nerve guidance conduit (NGC) that can regulate biological behavior of Schwann cells (SCs) and facilitate axonal regeneration through microenvironmental remodeling is beneficial for nerve regeneration and functional recovery. Gastrodin, a main constituent of a Chinese traditional herbal medicine, has been known to display several biological and pharmacological properties, especially antioxidative, anti-inflammatory and nerve regeneration. Herein, polyurethane (PU) NGCs modified by different weight ratio of Gastrodin (0, 1 and 5 wt%) were designed for sequential and sustainable drug release, that created a favorable microenvironment for nerve regeneration. The scaffold showed suitable pore structure and biocompatibility in vitro, and evidently promoted morphological and functional recovery of regenerated sciatic nerves in vivo. Compared to the PU and 1%Gastrodin/PU scaffolds, the 5%Gastrodin/PU significantly enhanced the proliferation, migration and myelination of SCs and up-regulated expression of neurotrophic factors, as well as induction of the differentiation of PC12 cells. Interestingly, the obvious anti-inflammatory response was observed in 5%Gastrodin/PU by reduced expression of TNF-α and iNOS, which also evidenced by the few fibrous capsule formation in the subcutaneous implantation. Such a construct presented a similarity to autograft in vivo repairing a 10 mm sciatic nerve defects. It was able to not only boost the regenerated area of nerve and microvascular network, but also facilitate functional axons growth and remyelination, leading to highly improved functional restoration. These findings demonstrate that the 5%Gastrodin/PU NGC efficiently promotes nerve regeneration, indicating their potential for use in peripheral nerve regeneration applications.

2.
Chemosphere ; 287(Pt 1): 131932, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34455122

RESUMO

Efficient elimination of fluoride from wastewater is an urgent need for ensuring water safety. In the present study, a stable and reusable nanocomposite (NCO@PAE) was synthesized by impregnating nanosized cerium oxides (NCO) inside a porous polystyrene anion exchanger (PAE) host for efficient fluoride removal from wastewater. The newly fabricated NCO@PAE exhibited excellent resistance to acid and alkali environment, allowing it to be utilized in a wide pH range (2-12). Fluoride uptake onto NCO@PAE was a pH-dependent process, which could reach the maximum capacity at pH 3.0. Compared with its host PAE, NCO@PAE showed conspicuous adsorption affinity towards fluoride in the coexistence of other competing anions at high concentrations. Adsorption kinetics confirmed its high efficiency for achieving equilibrium within 120 min. Fixed-bed adsorption runs demonstrated that the effective processing capacity of NCO@PAE for synthetic fluoride-containing wastewater (initial fluoride 2.5 mg/L) was about ~330 BV (bed volume), while only 22 BV for the host PAE. The exhausted NCO@PAE could be effectively revived by a simple in-situ desorption method for long-term cycle operation without conspicuous capacity loss. All the results indicated that NCO@PAE is a reliable and promising adsorbent for water defluoridation.

3.
J Ethnopharmacol ; 283: 114694, 2022 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-34601084

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: The flower buds of Tussilago farfara L. (Abbreviated as FTF) were widely used in traditional Chinese medicine (TCM) to treat respiratory diseases, including asthma, dry throat, great thirst, turbid saliva, stinky pus, and coughs caused by various causes. AIM OF STUDY: The aim of study is to explore the efficiency of FTF in vitro and in vivo for the treatment of lung inflammation, and to illustrate the possible mechanisms of FTF in treating inflammation-related respiratory diseases targeting NOD-like receptor 3 (NLRP3) inflammasome, nuclear factor erythroid 2-related factor 2 (Nrf2), and nuclear transcription factor-κB (NF-κB). METHODS: Lung inflammation model in vivo was induced by exposure of mice to cigarette smoke (CS) for two weeks. The levels of superoxide dismutase (SOD), malondialdehyde (MDA), inflammatory factors, and histology in lung tissues were investigated in presence or absence of ethanol extract of the flower buds of T. farfara L. (FTF-EtOH). In the cell-based models, nitric oxide (NO) assay, flow cytometry assay, enzyme-linked immunosorbent assay (Elisa), and glutathione (GSH) assay were used to explore the anti-inflammatory and anti-oxidant effects of FTF-EtOH. Possible anti-inflammatory mechanisms of FTF targeting NLRP3 inflammasome, Nrf2, and NF-κB have been determined using western blot, quantitative real-time reverse transcriptase-polymerase chain reaction (qRT-PCR), immunofluorescence assay, nuclear and cytoplasmic extraction, and ubiqutination assay. RESULTS: FTF-EtOH suppressed CS-induced overproduction of inflammatory factors [e.g., tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß)], and upregulation of the content of intracellular MDA in the lung homogenate of mice. In cell-based models, FTF-EtOH reduced the lipopolysaccharide (LPS)-induced overproduction of inflammatory factors, and attenuated the CS extract-induced overgeneration of reactive oxygen species (ROS). Furthermore, FTF-EtOH up-regulated Nrf2 and its downstream genes through enhancing the stability of Nrf2 protein, and inhibited the activation of NF-κB and NLRP3 inflammasome, which have been confirmed by detecting the protein levels in the mouse model. CONCLUSIONS: FTF-EtOH effectively attenuated lung inflammation in vitro and in vivo. The protection of FTF-EtOH against inflammation was produced by activation of Nrf2 and inhibitions of NF-κB and NLRP3 inflammasome. These datas definitely support the ethnopharmacological use of FTF as an anti-inflammatory drug for treating respiratory diseases in TCM.

4.
Nat Commun ; 12(1): 6629, 2021 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-34785664

RESUMO

The development of efficient and sustainable methods for carbon-phosphorus bond formation is of great importance due to the wide application of organophosphorus compounds in chemistry, material sciences and biology. Previous C-H phosphorylation reactions under nonelectrochemical or electrochemical conditions require directing groups, transition metal catalysts, or chemical oxidants and suffer from limited scope. Herein we disclose a catalyst- and external oxidant-free, electrochemical C-H phosphorylation reaction of arenes in continuous flow for the synthesis of aryl phosphorus compounds. The C-P bond is formed through the reaction of arenes with anodically generated P-radical cations, a class of reactive intermediates remained unexplored for synthesis despite intensive studies of P-radicals. The high reactivity of the P-radical cations coupled with the mild conditions of the electrosynthesis ensures not only efficient reactions of arenes of diverse electronic properties but also selective late-stage functionalization of complex natural products and bioactive compounds. The synthetic utility of the electrochemical method is further demonstrated by the continuous production of 55.0 grams of one of the phosphonate products.

5.
FEBS Lett ; 2021 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-34817071

RESUMO

The prevalence of non-alcoholic fatty liver disease (NAFLD) increases with aging. However, the mechanism of aging-related NAFLD remains unclear. Herein, we constructed an aging-related hepatic steatosis model and analyzed the differentially expressed proteins (DEPs) in livers from young and old mice using liquid chromatography-mass spectrometry. 588 aging-related DEPs and novel pathways were identified. Aminoacyl tRNA synthetase complex-interacting multifunctional protein 2 (AIMP2), the most significantly upregulated protein, promoted poly(ADP-ribose) polymerase 1 (PARP1) activation in aging-related hepatic steatosis. Additionally, mice liver-specific O-GlcNAcase knockout promoted AIMP2 and PARP1 expression. O-GlcNAc transferase overexpression and O-GlcNAcase inhibition by genetic or pharmaceutical manipulations increased AIMP2 and PARP1 levels in vitro. Mechanistically, O-GlcNAcylation increased AIMP2 protein stability, leading to its aggregation. Our study reveals O-GlcNAcylated AIMP2 as a novel pathogenic regulator of aging-related hepatic steatosis.

6.
Comput Biol Med ; 139: 105030, 2021 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-34800809

RESUMO

This paper presents a fully automatic method for multi-organ segmentation from 3D abdominal CT volumes. Firstly, spines and ribs are removed by exponential transformation and binarization to reduce the disturbance to subsequent segmentation. Then, a Local Linear Embedding (LLE)-based graph partitioning approach is employed to perform initial segmentation for liver, spleen, and bilateral kidneys simultaneously, and a novel segmentation refinement scheme is applied composed of hybrid intensity model, 3D Chan-Vese model, and histogram equalization-based organ separation algorithm. Finally, a pseudo-3D bottleneck detection algorithm is introduced for boundary correction. The proposed method does not require heavy training or registration process and is capable of dealing with shape and location variations as well as the weak boundaries of target organs. Experiments on XHCSU20 database show the proposed method is competitive with state-of-the-art methods with Dice similarity coefficients of 95.9%, 95.1%, 94.7%, and 94.5%, Jaccard indices of 92.2%, 90.8%, 90.0%, and 89.5%, and average symmetric surface distances of 1.1 mm, 1.0 mm, 0.9 mm and 1.1 mm, for liver, spleen, left and right kidneys, respectively, and the average running time is around 6 min for a CT volume. The accuracy, precision, recall, and specificity also maintain high values for each of the four organs. Moreover, experiments on SLIVER07 dataset prove its high efficiency and accuracy on liver-only segmentation.

7.
Front Oncol ; 11: 745699, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34804932

RESUMO

Introduction: The therapeutic cancer vaccine recombinant Epidermal Growth Factor (EGF)-CRM197 is a novel combined conjugate EGF with CRM197 as a carrier protein. Immunization with the EGF-CRM197 vaccine can induce high levels of neutralizing anti-EGF antibodies that inhibit EGF/EGFR signaling and thereby suppress growth of tumors that rely on this signaling pathway. Herein, we characterize the humoral immune responses elicited by the recombinant EGF-CRM197 vaccine in patients with advanced solid tumors in a phase I clinical trial and assess the safety, tolerability, and immunogenicity of this vaccine (CTR20190473). Methods: A total of 16 subjects were enrolled in this study. Under 6 + 3 design, patients in each dosing cohort were administrated subcutaneously at a dosage of 0.4 mg, 0.8 mg, and 1.6 mg, respectively. The patients received vaccinations for immune induction (once a week for 4 consecutive weeks) and booster vaccinations (once every 4 weeks). Safety evaluation was performed 1 week after the immune induction. Booster vaccination was given until the occurrence of disease progression, intolerance, withdrawal of informed consent by the patient, or negative result of anti-EGF test after two booster vaccinations. Results: Vaccination with EGF-CRM197 is safe and well-tolerated in patients with advanced solid tumors. Adverse reactions at the injection site were the most common adverse events (AEs) in recipients. No severe adverse reactions post vaccination were observed in the present study. Vaccinated patients developed a robust neutralizing antibody response triggered by EGF-CRM197 that significantly reduced the levels of EGF in serum. For lung cancer patients who were super good antibody responders (sGAR) to EGF-CRM197, the median progress-free survival (PFS) was 4.83 months, significantly longer than that of the good antibody responder (GAR) patients with lung cancer whose median PFS was 2.10 months (P=0.0018). The median overall survival (OS) of GAR lung cancer patients was 10.67 months while the OS) for sGAR lung cancer patients was not reached until analysis was performed. The median follow-up of the sGAR lung cancer patients was 14.6 months. Conclusion: Our study demonstrates that the recombinant EGF-CRM197 therapeutic cancer vaccine can induce a good immune response in patients with advanced solid tumors and is safe and well tolerated, which ensures further clinical development of the vaccine for extending the survival time of EGF-CRM197 sensitive patients with advanced solid tumors. Clinical Trial Registration: http://www.chinadrugtrials.org.cn, identifier CTR20190473, EGF-CRM197.

8.
Explore (NY) ; 2021 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-34810135

RESUMO

OBJECTIVE: The present study aimed to investigate the efficacy of using acupuncture combined with Bailemian capsule to treat cervical spondylosis by observing the improvement in the degree of headache, anxiety, and depression suffered by patients. METHODS: A total of 100 patients with cervical spondylosis of the cervical type were equally divided into a combination group and a control group using the random number table method. The patients in the combination group were treated with acupuncture combined with the oral administration of Bailemian capsule, while those in the control group were only treated with acupuncture. Patient self-assessment was conducted, comprising the visual analogue scale, the self-assessment scale for anxiety, and the self-assessment scale for depression. Before treatment and on the14th and 28th days of treatment, the therapeutic effects of the two treatment modalities on the cervical spondylosis and accompanying headache, anxiety, and depression were analyzed using the Hamilton anxiety scale, the Hamilton depression scale, the Pittsburgh sleep quality inventory, and the Neck Disability Index (%). RESULTS: There were statistically significant differences between the two groups in all seven indicators at the different treatment time points (p < 0.01). The seven indicators were significantly reduced in both groups on the 14th and 28th days of treatment compared with before the treatment. Moreover, except for the Neck Disability Index results at 14 days, which did not differ between the groups (p = 0.37), all the other indicators were significantly lower in the combination group than in the control group on the 14th and 28th days of treatment (p < 0.01), and at the end of the treatment, the therapeutic effect was significantly better in the combination group than in the control group (p = 0.006). CONCLUSION: Both acupuncture combined with Bailemian Capsule and acupuncture alone were effective in the treatment of cervical spondylosis, but the combination therapy was better than the acupuncture alone in improving the accompanying negative symptoms of headache, anxiety, and depression.

9.
Neurology ; 2021 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-34810247

RESUMO

BACKGROUND AND OBJECTIVE: Patients with earlier age at onset of sporadic Alzheimer's Disease (AD) are more likely than those with later onset to present with atypical clinical and cognitive features. We sought to determine if this age-related clinical and cognitive heterogeneity is mediated by different topographical distributions of tau-aggregate neurofibrillary tangles (NFTs) or by variable amounts of concomitant non-AD neuropathology. METHODS: The relative distribution of NFT density in hippocampus and midfrontal neocortex was calculated, and α-synuclein, TDP-43, and microvascular co-pathologies were staged, in patients with severe AD and age at onset of 51-60 (n=40), 61-70 (n=41), and >70 (n=40) years. Regression, mediation, and mixed effects models examined relationships of pathological findings with clinical features and longitudinal cognitive decline. RESULTS: Patients with later age at onset of AD were less likely to present with non-memory complaints (OR=0.46 per decade, 95%CI: 0.22 - 0.88), psychiatric symptoms (ß=-0.66, 95%CI: -1.15 - -0.17), and functional impairment (ß=-1.25, 95%CI: -2.34 - -0.16). TDP-43 (OR = 2.00, 95%CI: 1.23 - 3.35) and microvascular co-pathology (OR = 2.02, 95%CI: 1.24 - 3.40) were more common in later onset AD, and α-synuclein co-pathology was not related to age at onset. NFT density in Midfrontal cortex (ß = -0.51, 95% CI: -0.72 - -0.31) and Midfrontal/Hippocampal NFT ratio (ß = -0.18, 95% CI: -0.26 - -0.10) were lower in those with later age at onset. Executive function (ß = 0.48, 95% CI: 0.09 - 0.90) and visuospatial (ß = 0.97, 95% CI: 0.46 - 1.46) cognitive deficits were less impaired in patients with later age at onset. Mediation analyses showed that the effect of age at onset on severity of executive function deficits was mediated by Midfrontal/Hippocampal NFT ratio (ß = 0.21, 95% CI: 0.08 - 0.38) and not by concomitant non-AD pathologies. Midfrontal/Hippocampal NFT ratio also mediated an association between earlier age at onset and faster decline on tests of global cognition, executive function, and visuospatial abilities. DISCUSSION: Worse executive dysfunction and faster cognitive decline in people with sporadic AD with earlier rather than later age at onset is mediated by greater relative Midfrontal neocortical to hippocampal NFT burden and not by concomitant non-AD neuropathology.

10.
Proc Natl Acad Sci U S A ; 118(48)2021 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-34810257

RESUMO

Kinetochores, a protein complex assembled on centromeres, mediate chromosome segregation. In most eukaryotes, centromeres are epigenetically specified by the histone H3 variant CENP-A. CENP-T, an inner kinetochore protein, serves as a platform for the assembly of the outer kinetochore Ndc80 complex during mitosis. How CENP-T is regulated through the cell cycle remains unclear. Ccp1 (counteracter of CENP-A loading protein 1) associates with centromeres during interphase but delocalizes from centromeres during mitosis. Here, we demonstrated that Ccp1 directly interacts with CENP-T. CENP-T is important for the association of Ccp1 with centromeres, whereas CENP-T centromeric localization depends on Mis16, a homolog of human RbAp48/46. We identified a Ccp1-interaction motif (CIM) at the N terminus of CENP-T, which is adjacent to the Ndc80 receptor motif. The CIM domain is required for Ccp1 centromeric localization, and the CIM domain-deleted mutant phenocopies ccp1Δ. The CIM domain can be phosphorylated by CDK1 (cyclin-dependent kinase 1). Phosphorylation of CIM weakens its interaction with Ccp1. Consistent with this, Ccp1 dissociates from centromeres through all stages of the cell cycle in the phosphomimetic mutant of the CIM domain, whereas in the phospho-null mutant of the domain, Ccp1 associates with centromeres during mitosis. We further show that the phospho-null mutant disrupts the positioning of the Ndc80 complex during mitosis, resulting in chromosome missegregation. This work suggests that competitive exclusion between Ccp1 and Ndc80 at the N terminus of CENP-T via phosphorylation ensures precise kinetochore assembly during mitosis and uncovers a previously unrecognized mechanism underlying kinetochore assembly through the cell cycle.

11.
BMC Gastroenterol ; 21(1): 416, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34724892

RESUMO

BACKGROUND: MKI67 plays a vital role in the tumour microenvironment (TME) and congenital immunity. The present work focuses on exploring the prognosis prediction performance of MKI67 and its associations with T cell activity and immune infiltration within numerous cancers, especially hepatocellular liver carcinoma (LIHC). METHODS: Oncomine, GEPIA2, and HPA were adopted to analyse MKI67 levels in different types of cancers. The prognostic prediction performance of MKI67 was evaluated through the TCGA portal, GEPIA2, LOGpc, and Kaplan-Meier Plotter databases. The associations of MKI67 with related gene marker sets and immune infiltration were inspected through TISIDB, GEPIA2, and TIMER. We chose MKI67 to analyse biological processes (BPs) and KEGG pathways related to the coexpressed genes. Furthermore, the gene-miRNA interaction network for MKI67 in liver cancer was also examined based on the miRWalk database. RESULTS: MKI67 expression decreased in many cancers related to the dismal prognostic outcome of LIHC. We found that MKI67 significantly affected the prognosis of LIHC in terms of histology and grade. Increased MKI67 levels were directly proportional to the increased immune infiltration degrees of numerous immune cells and functional T cells, such as exhausted T cells. In addition, several critical genes related to exhausted T cells, including TIM-3, TIGIT, PD-1, LAG3, and CXCL13, were strongly related to MKI67. Further analyses showed that MKI67 was associated with adaptive immunity, cell adhesion molecules (CAMs), and chemokine/immune response signal transduction pathways. CONCLUSION: MKI67 acts as a prognostic prediction biomarker in several cancers, particularly LIHC. Upregulation of MKI67 elevates the degree of immune infiltration of many immune cell subtypes, including functional T cells, CD4+ T cells, and CD8+ T cells. Furthermore, MKI67 shows a close correlation with T cell exhaustion, which plays a vital role in promoting T cell exhaustion within LIHC. Detection of the MKI67 level contributes to prognosis prediction and MKI67 modulation within exhausted T cells, thus providing a new method to optimize the efficacy of anti-LIHC immunotherapy.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Biomarcadores Tumorais/genética , Linfócitos T CD8-Positivos , Humanos , Prognóstico , Microambiente Tumoral
12.
ACS Appl Mater Interfaces ; 13(45): 54069-54078, 2021 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-34748308

RESUMO

Rechargeable lithium-ion batteries using high-capacity anodes and high-voltage cathodes can deliver the highest possible energy densities among all electrochemical devices. However, there is no single electrolyte with a wide and stable electrochemical window that can accommodate both a high-voltage cathode and a low-voltage anode so far. Here, we propose that a strategy of using a hybrid electrolyte should be applied to realize the full potential of a Ni-rich LiNi0.8Co0.1Mn0.1O2 (NCM811)-silicon/carbon (Si/C) full cell by simultaneously achieving optimal redox chemistry at both the NCM811 cathode and the Si/C anode. The hybrid-electrolyte design spatially separates the cathodic electrolytes from anodic electrolytes by a Nafion-based separator. The ionic liquid electrolyte (LiTFSI-Pyr13TFSI) on the cathode side can stand high work potentials and form a stable cathodic electrolyte intermediate (CEI) on NCM811. Meanwhile, a stable solid electrolyte intermediate (SEI) and high cycling stability can also be achieved on the anode side, enabled by a localized high concentration of ether-based electrolytes (LiTFSI-DME/HFE). The decoupled NCM811-Si/C full cell exhibits excellent long-term cycling performance with ultrahigh capacity retention for over 1000 cycles, thanks to the synergy of the cathode-side and anode-side electrolytes. This hybrid-electrolyte strategy has been proven to be applicable for other high-performance battery systems such as dual-ion batteries (DIB).

13.
PLoS One ; 16(11): e0260017, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34793486

RESUMO

Flower bud development is a defining feature of walnut, which contributes to the kernel yield, yield stability, fruit quality and commodity value. However, little is known about the mechanism of the flower bud development in walnut. Here, the stages of walnut female flower bud development were divided into five period (P01-05) by using histological observation. They were further studied through PacBio Iso-Seq and RNA-seq analysis. Accordingly, we obtained 52,875 full-length transcripts, where 4,579 were new transcripts, 3,065 were novel genes, 1,437 were consensus lncRNAs and 20,813 were alternatively spliced isoforms. These transcripts greatly improved the current genome annotation and enhanced our understanding of the walnut transcriptome. Next, RNA sequencing of female flower buds at five periods revealed that circadian rhythm-plant was commonly enriched along with the flower bud developmental gradient. A total of 14 differentially expressed genes (DEGs) were identified, and six of them were confirmed by real-time quantitative analysis. Additionally, six and two differentially expressed clock genes were detected to be regulated by AS events and lncRNAs, respectively. All these detected plant circadian genes form a complex interconnected network to regulate the flower bud development. Thus, investigation of key genes associated with the circadian clock could clarify the process of flower bud development in walnut.

14.
Int J Nurs Stud ; 125: 104110, 2021 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-34736073

RESUMO

BACKGROUND: Mild cognitive impairment affects 36% of people aged ≥65 years in China, around 50% of whom will develop dementia within 3 years. Early intervention can slow disease progression and delay the onset of dementia; however, whether a multicomponent intervention can decelerate the progression of mild cognitive impairment remains unknown. OBJECTIVE: To evaluate the effects of a multicomponent intervention to slow mild cognitive impairment progression in Chinese patients. DESIGN: Randomized controlled trial. SETTING(S) AND PARTICIPANTS: This study was conducted in two large regional communities in Guangzhou, China. Patients aged ≥ 65 years diagnosed with mild cognitive impairment were included. METHODS: A total of 112 eligible participants were assigned to receive either a 6-month multicomponent intervention or usual care from September 2019 until January 2021. Data were collected at the beginning of the study and at 1, 3, and 6 months thereafter. The primary outcomes were cognitive function, comprehensive physical capacity, depression, and quality of life. Analysis followed the intention-to-treat principle. A generalized estimating equation was used to determine intervention effects. RESULTS: At baseline, clinical characteristics did not differ significantly between groups. Significant interaction effects between time and group were detected (p < 0.001), indicating that the scores of five outcomes (cognitive function, short physical performance battery, timed up and go test, quality of life, and depression) of intervention and control groups changed differently over time. Participants in the intervention group were found to have a significantly greater improvement in cognitive function, physical function, quality of life, and fewer depression symptoms compared with the control group at baseline and follow-up periods. CONCLUSIONS: This study demonstrates the beneficial effects of a multicomponent intervention on cognitive function, physical function, depression symptoms, and quality of life in people with mild cognitive impairment in the East Asia region. The effectiveness and feasibility of this intervention program suggest that its application should be promoted in community settings to delay the progression of disease in people with mild cognitive impairment. Registration number:ChiCTR1900026042 Tweetable abstract: The multicomponent intervention improves cognitive/physical function, depression, and quality of life, slowing cognitive impairment progression.

15.
Adv Mater ; : e2107161, 2021 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-34767279

RESUMO

The release of tumor-associated antigens (TAAs) and their cross-presentation in dendritic cells (DCs) are crucial for radio-immunotherapy. However, the irradiation resistance of tumor cells usually results in limited TAA generation and release. Importantly, TAAs internalized by DCs are easily degraded in lysosomes, resulting in unsatisfactory extent of TAA cross-presentation. Herein, an antigen-capturing stapled liposome (ACSL) with a robust structure and bioactive surface is developed. The ACSLs capture and transport TAAs from lysosomes to the cytoplasm in DCs, thereby enhancing TAA cross-presentation. l-arginine encapsulated in ACSLs induces robust T cell-dependent antitumor response and immune memory in 4T1 tumor-bearing mice after local irradiation, resulting in significant tumor suppression and an abscopal effect. Replacing l-arginine with radiosensitizers, photosensitizers, and photothermal agents may make ACSL a universal platform for the rapid development of various combinations of anticancer therapies.

16.
Oral Dis ; 2021 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-34773344

RESUMO

Accumulated evidence indicates that immune cell populations play pivotal roles in the process of tumor initiation, progression, recurrence, metastasis, and immune escape. Ferroptosis is a form of regulating cell death in the nexus between metabolism, redox biology, and human health. Ferroptosis is considered as a vital important event in HNSCC, but the underling mechanism of regulating immune cell populations remains poorly understood. Our tissue microarray study showed that patients with high expression of GPX4 were related to poor survival. Moreover, the expression of GPX4 has been negatively associated with immunogenic cell death-related protein calreticulin in HNSCC tissue cohort. Further, RSL3 was used to induce ferroptosis in HNSCC xenograft of C3H/He mouse. We found that the occurrence of ferroptosis had significantly reduced the number of myeloid-derived suppressor cells (MDSCs) and tumor-associated M2-like macrophages (M2 TAMs) in tumor microenvironment. Meanwhile, the tumor-infiltrating CD4+ and CD8+ T cells were increased. And the calreticulin and HMGB1 may be potential candidate proteins improving the immunosuppressive tumor microenvironment. Taken together, our project suggests that ferroptosis can promote anti-tumor immune response by reversing immunosuppressive microenvironment, indicating that ferroptosis inducer is a promising therapeutic strategy in HNSCC.

17.
Lasers Surg Med ; 2021 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-34806777

RESUMO

PURPOSE: To conduct keratometry and investigate the ultrastructural changes after microwave thermokeratoplasty (MTK) in rabbit eyes. METHODS: Eighteen New Zealand rabbits (18 eyes) were recruited for this study. Ten eyes were chosen for slit-lamp photography and corneal topography at 1 day, 1 week, 1 month, 3 months, and 6 months postoperatively. Two rabbits were sacrificed on 1 day, 1 week, 1 month, and 3 months postoperatively. All remaining rabbits were sacrificed at 6 months postoperatively. The cornea was observed using hematoxylin and eosin staining and transmission electron microscopy. Data are expressed as mean ± standard deviation. p value was determined using repeated-measures analysis of variance. RESULTS: Corneal edema, disorganized corneal collagen fibers in the heated area, and necrotic fibroblasts were observed at 1 day and 1 week postoperatively. At 1 month postoperatively, corneal edema was not observed, and corneal cell morphology was normal. Moreover, corneal collagen fibers in the heated area shrunk and tended to be organized. The K1 and K2 values significantly decreased from 49.0 ± 1.2 D and 50.5 ± 0.9 D preoperatively to 40.3 ± 1.2 D and 43.2 ± 0.8 D 6 months postoperatively, respectively. The corneal thickness was 353.1 ± 9.3 µm preoperatively and 317.8 ± 27.7 µm at 6 months postoperatively; the difference was not statistically significant. CONCLUSIONS: Corneal keratometry showed flattening after MTK. Moreover, corneal collagen fibers in the heated area shrunk and tended to be organized at 6 months postoperatively. Further studies are required to determine the safety and stability of MTK.

18.
Int Endod J ; 2021 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-34807471

RESUMO

AIM: To evaluate the effects of hsa-miRNA-143-3p on the cytodifferentiation of human stem cells from the apical papillary (hSCAPs) and the post-transcriptional regulation of Nuclear factor I-C (NFIC). METHODOLOGY: miRNA expression profiles in human immature permanent teeth and during hSCAP differentiation were examined. hSCAPs were treated with miR-143-3p overexpression or silencing viruses, and the proliferation and odontogenic and osteogenic differentiation of these stem cells, and the involvement of the NFIC pathway, were investigated. Luciferase reporter and NFIC mutant plasmids were used to confirm NFIC mRNA as a direct target of miR-143-3p. NFIC expression analysis in the miR-143-3p overexpressing hSCAPs was used to investigate whether miR-143-3p functioned by targeting NFIC. Student's t-test and chi-square tests were used for statistical analysis. RESULTS: miR-143-3p expression was screened by microarray profiling and was found to be significantly reduced during hSCAP differentiation (P < 0.05). Overexpression of miR-143-3p inhibited the mineralization of hSCAPs significantly (P < 0.05) and downregulated the levels of odontogenic differentiation markers [NFIC (P < 0.05), DSP (P < 0.01) and KLF4 (P < 0.01)], whereas silencing of miR-143-3p had the opposite effect. The luciferase reporter gene detection and bioinformatic approaches identified NFIC mRNA as a potential target of miR-143-3p. NFIC overexpression reversed the inhibitory effect of miR-143-3p on the odontogenic differentiation of hSCAPs. CONCLUSIONS: miR-143-3p maintained the stemness of hSCAPs and modulated their differentiation negatively by directly targeting NFIC. Thus, inhibition of this miRNA represents a potential strategy to promote the regeneration of damaged tooth roots.

19.
Int J Gen Med ; 14: 7855-7860, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34795506

RESUMO

Introduction: The association between cancer and hyper-coagulability is well known. However, the association between melanoma and venous thromboembolism (VTE) has not been identified. Methods: We studied the national inpatient sample (NIS) which compromise 20% of US hospitalization to better characterize melanoma and VTE. We analyzed the data between 2010 and 2014 using ICD-9 codes. Results: Melanoma patients were grouped into presence/absence of VTE. Multiple logistic regression was used to obtain the odds ratio (OR) to compare the mortality of the inpatient, total charges, length of stay (LOS), and disability at discharge. A total of 61,812 melanoma patients were identified, of which 5.2% were hospitalized for VTE. The presence of VTE was associated with a remarkable higher rate of discharge with a moderate to severe disability (57.5% vs 41.4%, P<0.001), in-hospital stroke (7.6% vs 4.9%, P<0.001), and in-hospital mortality (8.8% vs 5.1%, P<0.001). Costs of hospitalization (64,720$ vs 46,606, P<0.001) and LOS (5 vs 3 days, P<0.001) were significantly higher as well in the VTE group. After adjusting for common confounder, VTE was found to be an independent predictor of mortality (OR = 1.596, 95% CI [1.399-1.821], P<0.001). Conclusion: In summary, melanoma patients with VTE had higher inpatient mortality, LOS, higher hospital cost, and a higher degree of disability upon discharge.

20.
Front Immunol ; 12: 760954, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34759932

RESUMO

Background: The molecular mechanisms of acute otitis media (AOM) development, and the intercellular crosstalk within the multicellular ecosystem of AOM, are not clear. Methods: We established a model of AOM in rats (with normal rats as controls) and undertook single-cell RNA sequencing (scRNA-seq) for the middle-ear mucosa (MEM). Cell clustering and trajectory analyses were undertaken using Seurat and Monocle 2 packages in R software. Pathway analyses were done by gene set enrichment analysis (GSEA). Cell-cell interactions were inferred by CellChat. Cell scores were calculated to identify cells with dual-feature. Results: A total of 7023 cells from three samples of inflamed MEM and 5258 cells from three samples of healthy MEM underwent scRNA-seq, which identified 20 cell clusters belonging to eight major cell types. After exposure to lipopolysaccharide, the MEM underwent significant conversion of cell types characterized by rapid infiltration of macrophages and neutrophils. M2 macrophages seemed to play a key part in inflammatory intercellular crosstalk, which facilitated the maintenance and proliferation of macrophages, cell chemotaxis, and regulation of the proinflammatory activities of cytokines. Three rare cell clusters with phagocytosis-related dual-feature were also identified. They coexisted with professional phagocytes in the MEM, and displayed distinct immunoregulatory functions by maintaining a normal immune microenvironment or influencing inflammation progression. Conclusions: Macrophages might be the "master" initiators and regulators of the inflammatory response of the MEM to external stimuli. And their functions are fulfilled by a specific polarization status (M2) and sophisticated intercellular crosstalk via certain signaling pathways. Besides, the coexistence of professional phagocytes and non-professional phagocytes as well as their interplay in the MEM provides new clues for deciphering the underlying pathogenic mechanisms of AOM.

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