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1.
Artigo em Inglês | MEDLINE | ID: mdl-34807583

RESUMO

Stroke is the second leading cause of death globally and the most common cause of severe disability. Several barriers need to be addressed more effectively to treat stroke, including efficient delivery of therapeutic agents, rapid release at the infarct site, precise imaging of the infarct site, and drug distribution monitoring. The present study aimed to develop a bio-responsive theranostic nanoplatform with signal-amplifying capability to deliver rapamycin (RAPA) to ischemic brain tissues and visually monitor drug distribution. A pH-sensitive theranostic RAPA-loaded nanoparticle system was designed since ischemic tissues have a low-pH microenvironment compared with normal tissues. The nanoparticles demonstrated good stability and biocompatibility and could efficiently load rapamycin, followed by its rapid release in acidic environments, thereby improving therapeutic accuracy. The nano-drug-delivery system also exhibited acid-enhanced magnetic resonance imaging (MRI) and near-infrared fluorescence (NIRF) imaging signal properties, enabling accurate multimodal imaging with minimal background noise, thus improving drug tracing and diagnostic accuracy. Finally, in vivo experiments confirmed that the nanoparticles preferentially aggregated in the ischemic hemisphere and exerted a neuroprotective effect in rats with transient middle cerebral artery occlusion (tMCAO). These pH-sensitive multifunctional theranostic nanoparticles could serve as a potential nanoplatform for drug tracing as well as the treatment and even diagnosis of acute ischemic stroke. Moreover, they could be a universal solution to achieve accurate in vivo imaging and treatment of other diseases.

2.
J Asian Nat Prod Res ; : 1-7, 2021 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-34605341

RESUMO

One new ionone glycoside, named centrantheroside F (1), together with 9 known compounds (2-10), were isolated from the roots of Centranthera grandiflora. Their structures were determined by spectroscopic data analyses and comparing with the literature data. The absolute configuration of 1 was confirmed via 2 D NMR and electronic circular dichroism (ECD). All isolated compounds were evaluated for their inhibitory activity on lipopolysaccharide (LPS)-induced nitric oxide (NO) production.

3.
Pharmacol Ther ; : 107983, 2021 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-34480962

RESUMO

Fibrosis, which is characterized by excessive extracellular matrix (ECM) deposition, is a wound-healing response to organ injury and may promote cancer and failure in various organs, such as the heart, liver, lung, and kidney. Aging associated with oxidative stress and inflammation exacerbates cellular dysfunction, tissue failure, and body function disorders, all of which are closely related to fibrosis. Sirtuin-1 (SIRT1) is a class III histone deacetylase that regulates growth, transcription, aging, and metabolism in various organs. This protein is downregulated in organ injury and fibrosis associated with aging. Its expression and distribution change with age in different organs and play critical roles in tissue oxidative stress and inflammation. This review first described the background on fibrosis and regulatory functions of SIRT1. Second, we summarized the relationships of SIRT1 with other proteins and its protective action during fibrosis in the heart, liver, lung and kidney. Third, the activation of SIRT1 in therapies of tissue fibrosis, especially in liver fibrosis and aging-related tissue injury, was analyzed. In conclusion, SIRT1 targeting may be a new therapeutic strategy in fibrosis.

4.
Carbohydr Polym ; 273: 118538, 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34560950

RESUMO

Chinese quince seed gum (CQSG) extracted under water-, alkali- and acid- conditions at 25, 50, and 80 °C, were evaluated in terms of yield, monosaccharide composition, molecular distribution, thermal gravimetry, emulsifying stability, rheological properties, and free radical scavenging ability. The results showed that the yield of CQSG increased to 3.9% after water extraction at 80 °C. Alkali and acid treatments promoted the conversion of neutral sugars to the uronic acid branch. Regardless of the extraction temperature, the xylose chain was the main component (35%-40%); however, a reduction was observed as the extraction temperature increased to 80 °C. All CQSG solutions extracted under these isolation conditions exhibited non-Newtonian rheological behavior. Compared to water-extracted samples, the alkali-extracted samples showed the worst thermal stability, while the acid-treated samples showed the worst emulsifying stability. This study provides theoretical support for the potential application of CQSG polysaccharides in the food and pharmaceutical industries.

5.
Cell Death Dis ; 12(10): 883, 2021 09 27.
Artigo em Inglês | MEDLINE | ID: mdl-34580275

RESUMO

Protein phosphatase 6 (PP6) is a member of the PP2A-like subfamily, which plays significant roles in numerous fundamental biological activities. We found that PPP6C plays important roles in male germ cells recently. Spermatogenesis is supported by the Sertoli cells in the seminiferous epithelium. In this study, we crossed Ppp6cF/F mice with AMH-Cre mice to gain mutant mice with specific depletion of the Ppp6c gene in the Sertoli cells. We discovered that the PPP6C cKO male mice were absolutely infertile and germ cells were largely lost during spermatogenesis. By combing phosphoproteome with bioinformatics analysis, we showed that the phosphorylation status of ß-catenin at S552 (a marker of adherens junctions) was significantly upregulated in mutant mice. Abnormal ß-catenin accumulation resulted in impaired testicular junction integrity, thus led to abnormal structure and functions of BTB. Taken together, our study reveals a novel function for PPP6C in male germ cell survival and differentiation by regulating the cell-cell communication through dephosphorylating ß-catenin at S552.

6.
Artigo em Inglês | MEDLINE | ID: mdl-34433394

RESUMO

BACKGROUND: Recurrent miscarriage (RM) affects 1% to 5% of couples, and the mechanisms still stay unclear. In this study, we explored the underlying molecular mechanism and potential molecular biomarkers of RM as well as constructed a miRNA-mRNA regulation network. METHODS: The microarray datasets GSE73025 and GSE22490, which represent mRNA and miRNA profiles, respectively, were downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) with p-value < 0.05 and fold-change > 2 were identified while the miRNAs with p-value < 0.05 and fold-change > 1.3 were considered as significant differentially expressed miRNAs (DEMs). RESULTS: A total of 373 DEGs, including 218 up-regulated genes and 155 down-regulated genes, were identified, while 138 up-regulated and 68 down-regulated DEMs were screened out. After functional enrichment analysis, we found GO biological process (BP) terms significantly enriched in the Fc-gamma receptor signaling pathway involved in phagocytosis. Moreover, signaling pathway analyses indicated that the neurotrophin signaling pathway (hsa04722) was the top KEGG enrichment. 6 hub genes (FPR1, C5AR1, CCR1, ADCY7, CXCR2, NPY) were screened out to construct a complex regulation network in RM because they had the highest degree of affecting the network. Besides, we constructed miRNA-mRNA network between DEMs target genes and DEGs in RM, including hsa-miR-1297- KLHL24 and hsa-miR-548a-5p-KLHL24 pairs. CONCLUSIONS: In conclusion, the novel differentially expressed molecules in the present study could provide a new sight to explore the pathogenesis of RM as well as potential biomarkers and therapeutic targets for RM diagnosis and treatment.

7.
Artigo em Inglês | MEDLINE | ID: mdl-34394393

RESUMO

Methods: A comprehensive strategy based on several Chinese herb databases and chemical compound databases was established to screen active compounds of ZSYTP and predict target genes. For network pharmacological analysis, network construction and gene enrichment analysis were conducted and further verified by molecular docking. Results: A total of 476 target genes of ZSYTP were obtained from 205 active compounds. 13 herbs of ZSYTP overlapped on 8 active compounds based on the compound-target-disease network (C-T network). 20 biological processes and 9 pathways were strongly connected to the targets of ZSYTP in treating POI, including negative regulation of gene expression, mRNA metabolic process, hypoxia-inducible factor 1 (HIF-1) signaling pathway, and gluconeogenesis. Finally, molecular docking was visualized. Conclusion: Intriguingly, the signal pathways and biological processes uncovered in this study implicate inflamm-aging and glucose metabolism as potential pathological mechanisms of POI. The therapeutic effect of ZSYTP could be mediated by regulating glucose metabolism and HIF-1 signal pathway. Collectively, this study sheds light on the therapeutic potential of ZSYTP on POI.

8.
J Innate Immun ; 13(6): 333-344, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34289483

RESUMO

Eosinophil (Eo) degranulation plays a central role in the initiations of allergic attacks. Flagellin (FGN), the major component of bacterial flagella, has immune regulatory functions. This study aims to investigate the role of FGN in alleviating the allergic reaction by stabilizing Eos. A toll-like receptor 5-knockout mouse strain was employed to test the role of FGN in stabilizing Eos. An airway allergy mouse model was developed to test the administration of FGN in alleviating the airway allergy by stabilizing Eos. The results showed that FGN was required in stabilizing Eos in the airway tissues. FGN prevented specific antigen-induced Eo activation. Oxidative stress was associated with the antigen-induced Eo activation that could be counteracted by the presence of FGN. The FGN levels were lower and chymase levels were higher in the airway tissues of mice with allergic inflammation. Negative correlation was detected between the data of FGN and chymase in the lung tissues. Chymase physically contacted FGN to speed up its degradation. The administration of FGN alleviated experimental allergic inflammation in the mouse airways by stabilized Eos in the lung tissues. In conclusion, FGN contributes to Eo stabilization. The administration of FGN alleviates the experimental airway allergy. The data suggest that FGN can be a candidate to be employed in the treatment of allergic disorders.

9.
BMC Pregnancy Childbirth ; 21(1): 418, 2021 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-34090383

RESUMO

BACKGROUND: Premature ovarian insufficiency (POI) is characterized by impairment of ovarian function on a continuum before the age of 40 years. POI is affected by multiple factors. Considering new insights from recent gut microbiome studies, this study aimed to investigate the relationship between gut microbial community structure and POI. METHODS: Subjects were recruited at the Shenzhen Maternity & Child Healthcare Hospital. Fecal microbial community profiles of healthy women (n = 18), women with POI (n = 35) were analyzed using 16S rRNA gene sequencing based on Illumina NovaSeq platform. RESULTS: Compared to the controls, the serum levels of FSH, LH, T and FSH/LH ratio significantly increased in women with POI, whereas E2 and AMH decreased significantly. Higher weighted UniFrac value was observed in POI women compared with healthy women. Phylum Firmicutes, genera Bulleidia and Faecalibacterium were more abundant in healthy women, while phylum Bacteroidetes, genera Butyricimonas, Dorea, Lachnobacterium and Sutterella enriched significantly in women with POI. Moreover, these alterations of the gut microbiome in women with POI were closely related to FSH, LH, E2, AMH level and FSH/LH ratio. CONCLUSIONS: Women with POI had altered microbial profiles in their gut microbiome, which were associated with serum hormones levels. These results will shed a new light on the pathogenesis and treatment for POI.


Assuntos
Microbioma Gastrointestinal , Insuficiência Ovariana Primária , Adulto , Estudos de Casos e Controles , Estradiol/sangue , Fezes/microbiologia , Feminino , Humanos , RNA Ribossômico 16S/análise , Adulto Jovem
10.
Small ; 17(26): e2100732, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34080772

RESUMO

The rational synthesis of single-layer noble metal directly anchored on support materials is an elusive target to accomplish for a long time. This paper reports well-defined single-layer Pt (Pt-SL) clusters anchored on ultrathin TiO2 nanosheets-as a new frontier in electrocatalysis. The structural evolution of Pt-SL/TiO2 via self-assembly of single Pt atoms (Pt-SA) is systematically recorded. Significantly, the Pt atoms of Pt-SL/TiO2 possess a unique electronic configuration with PtPt covalent bonds surrounded by abundant unpaired electrons. This Pt-SL/TiO2 catalyst presents enhanced electrochemical performance toward diverse electrocatalytic reactions (such as the hydrogen evolution reaction and the oxygen reduction reaction) compared with Pt-SA, multilayer Pt nanoclusters, and Pt nanoparticles, suggesting an efficient new type of catalyst that can be achieved by constructing single-layer atomic clusters on supports.

11.
Opt Express ; 29(11): 16804-16819, 2021 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-34154234

RESUMO

The description of deformable mirror (DM) surface, which is usually a complex freeform surface, affects the measurement speed and accuracy in a real-time interferometric measurement system with a DM as the dynamic compensator. We propose an accurate and fast description method with automatically configurable Gaussian radial basis function. The distribution and shape factors of GRBFs are related to the complexity of the surface with sufficient flexibility to improve the accuracy, and the fitting results are automatically obtained using a traversal optimization algorithm, which can improve the fitting speed by reducing the number of time-consuming calculations. The feasibility is verified by numerical and practical experiment.

12.
Stem Cell Res Ther ; 12(1): 257, 2021 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-33933157

RESUMO

BACKGROUND: Cutaneous wound healing and regeneration have become a recognized health challenge in the world, which causes severe damage to the mental and physical health of patients. Human adipose-derived mesenchymal stem cells (hADSC) play an essential role in wound healing via their paracrine function. Exosomes secreted by hADSC may contribute to this progress. In this study, we investigated the potential clinical application roles of hADSC and hADSC-derived exosomes (hADSC-Exo) in cutaneous wound healing. METHODS: hADSC-Exo was isolated from human hADSC by ultracentrifugation. Mice were subjected to a full-thickness skin biopsy experiment and treated with either control vehicle or hADSC or hADSC-Exo by smearing administration (sm) or subcutaneous administration (sc) or intravenous administration (iv). The efficacy of hADSC and hADSC-Exo on wound healing was evaluated by measuring wound closure rates, histological analysis. RESULTS: Combined application of local hADSC-Exo smearing and hADSC/hADSC-Exo intravenous administration offered the additional benefit of promoting wound healing, accelerating re-epithelialization, reducing scar widths, and enhancing angiogenesis and collagen synthesis. Either topical application of hADSC-Exo or systemic administration with hADSC/hADSC-Exo appeared more effective in stimulating cell proliferation, inhibiting cell apoptosis and inflammation, and promoting skin elasticity and barrier integrity, with increased genes expression of PCNA, VEGF, collagen III, Filaggrin, Loricrin, and AQP3, with decreased genes expression of TNF-alpha. CONCLUSION: Our findings suggest that the combined administration of hADSC/hADSC-Exo can facilitate cutaneous wound healing and reduce scar formation. These data provide the first evidence for the feasibility of smearing of hADSC-Exo as a cell-free therapy in treating cutaneous wounds, and the potential clinical value of combined administration of hADSC/hADSC-Exo.


Assuntos
Exossomos , Células-Tronco Mesenquimais , Animais , Proliferação de Células , Humanos , Camundongos , Pele , Cicatrização
14.
Appl Opt ; 60(6): 1550-1557, 2021 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-33690488

RESUMO

A simultaneous phase-shifting interferometer with a monitored spatial light modulator (SLM) flexible reference mirror is proposed to balance the flexibility and accuracy of aspheric-surface in-process measurements. In this method, polarization simultaneous phase-shifting camera systems are applied to reduce the influence of environmental vibrations on the in-process measurements. An SLM reference mirror is employed to improve the flexibility of in-process measurements. A device is integrated to monitor the SLM surface in order to improve measurement accuracy caused by the spatial phase nonuniformity and modulation instability of the SLM. Thus, the SLM surface is monitored and the aspheric surface is measured simultaneously in only one interferometer, which presents the advantages of a compact structure and simple calibration. A flat acrylic mirror with an unknown surface figure error is measured by the proposed interferometer. Cross tests demonstrate the feasibility of this interferometer.

15.
BMC Nurs ; 20(1): 51, 2021 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-33757518

RESUMO

BACKGROUND: The core nursing outcomes for laryngeal carcinoma in China needed further screening and revision. This study aimed to evaluate and revise a questionnaire according to the "Core Nursing Outcomes for Otorhinolaryngology Head-Neck" of the Nursing Outcomes Classification (NOC, 5th Edition), and determine suitable postoperative nursing outcomes for patients with laryngeal carcinoma in China. METHODS: The commonly used postoperative nursing outcomes for laryngeal carcinoma were screened using a questionnaire given to 93 nurses. An initial expert consultation questionnaire was constructed to discuss the indicators for each nursing outcome. A total of 20 experts were identified using the Delphi method, and their recommendations and revisions on the selected nursing outcomes were collected. RESULTS: A total of 14 postoperative core nursing outcomes and 69 indicators were identified for postoperative patients with laryngeal carcinoma, which are subordinate to 4 domains of the NOC: "Physiologic Health", "Psychosocial Health", "Health Knowledge & Behavior", and "Perceived Health". CONCLUSIONS: The screening and revision of the NOC outcomes and indicators of the Delphi method could be applied to assess the effect of nursing intervention and the quality of the nursing service in China.

16.
J Gen Intern Med ; 36(5): 1292-1301, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33686587

RESUMO

BACKGROUND: The COVID-19 pandemic has resulted in negative impacts on the economy, population health, and health-related quality-of-life (HRQoL). OBJECTIVE: To assess the impact of COVID-19 on US population HRQoL using the EQ-5D-5L. DESIGN: We surveyed respondents on physical and mental health, demographics, socioeconomics, brief medical history, current COVID-19 status, sleep, dietary, financial, and spending changes. Results were compared to online and face-to-face US population norms. Predictors of EQ-5D-5L utility were analyzed using both standard and post-lasso OLS regressions. Robustness of regression coefficients against unmeasured confounding was analyzed using the E-Value sensitivity analysis. SUBJECTS: Amazon MTurk workers (n=2776) in the USA. MAIN MEASURES: EQ-5D-5L utility and VAS scores by age group. KEY RESULTS: We received n=2746 responses. Subjects 18-24 years reported lower mean (SD) health utility (0.752 (0.281)) compared with both online (0.844 (0.184), p=0.001) and face-to-face norms (0.919 (0.127), p<0.001). Among ages 25-34, utility was worse compared to face-to-face norms only (0.825 (0.235) vs. 0.911 (0.111), p<0.001). For ages 35-64, utility was better during pandemic compared to online norms (0.845 (0.195) vs. 0.794 (0.247), p<0.001). At age 65+, utility values (0.827 (0.213)) were similar across all samples. VAS scores were worse for all age groups (p<0.005) except ages 45-54. Increasing age and income were correlated with increased utility, while being Asian, American Indian or Alaska Native, Hispanic, married, living alone, having history of chronic illness or self-reported depression, experiencing COVID-19-like symptoms, having a family member diagnosed with COVID-19, fear of COVID-19, being underweight, and living in California were associated with worse utility scores. Results were robust to unmeasured confounding. CONCLUSIONS: HRQoL decreased during the pandemic compared to US population norms, especially for ages 18-24. The mental health impact of COVID-19 is significant and falls primarily on younger adults whose health outcomes may have been overlooked based on policy initiatives to date.


Assuntos
COVID-19 , Saúde da População , Adolescente , Adulto , Idoso , Nível de Saúde , Humanos , Pessoa de Meia-Idade , Pandemias , Qualidade de Vida , SARS-CoV-2 , Inquéritos e Questionários , Adulto Jovem
17.
Immunol Lett ; 230: 49-58, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33385440

RESUMO

BACKGROUND: Integrin αvß6 can convert the transforming growth factor (TGF)-ß precursor to the mature form. Resiquimod (R848) can generate TGF-ß-producing regulatory T cells (Treg). Thus, to concurrent administration of specific antigen and R848 may generate antigen-specific Tregs, that is expected to restore immune tolerance in subjects with airway allergic diseases (AAD). METHODS: A bio-nanoparticle, designated Rexo, containing an antigen/MHC II complex and R848, was naturally assembled in dendritic cells, that was released as an exosome. An AAD mouse model was developed used to test the effects of Rexo on restoring the immune tolerance in the airways. RESULTS: Exposure to R848 failed to induce Tregs in the ß6-deficient mouse airway tissues, that were successfully induced in wild type mice. The results were validated inin vitro experiments. R848 activated the TLR7/MyD88/p38 signal pathway to increase the αvß6 levels in CD4+ T cells, the αvß6 then converted the TGF-ß precursor to its mature form, and thus, induced Treg generation. Administration of Rexo restored the antigen-specific immune tolerance in the airways manifesting efficiently suppressing experimental AAD by inducing antigen-specific Tregs in the airways and inhibiting antigen-specific Th2 response. CONCLUSIONS: Rexos can inhibit experimental AAD via inducing antigen-specific Tregs to restore immune tolerance in the airway tissues, suggesting that Rexos have the translational potential to be used in the treatment of AAD.

18.
J Toxicol ; 2021: 6290524, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33505465

RESUMO

The objective of this work was to explore the ability of lactic acid bacteria strains to bind benzo(a)pyrene (B(a)P) existing in PM2.5. In this study, we examined the ability of Lactobacillus acidophilus NCFM to bind B(a)P in the simulated PM2.5 environment. Among the tested 5 strains, Lactobacillus acidophilus NCFM exhibited the best capacity to bind B(a)P, and its B(a)P binding percentage was 60.00%. Simulations of organic and inorganic systems which represent PM2.5 indicated that B(a)P could be absorbed by strain L. acidophilus NCFM. For the inorganic system of pH 5, L. acidophilus NCFM bound 92.74% B(a)P with a cell concentration of 1 × 1010 cfu/mL at 37°C for 8 hr. Regarding the organic system with pH 6, 73.00% B(a)P was bound by strain L. acidophilus NCFM after this bacterium was incubated at 37°C for 10 min. A quick B(a)P binding by this probiotic bacterium took place in the organic system. The removal of B(a)P from PM2.5 was significantly related to incubation time, cultivation temperature, pH, and cell concentration. Thus, our finding shows that long-term consumption of L. acidophilus NCFM is beneficial for the reduction of B(a)P towards the population who are exposed to PM2.5, although the ability of this bacterium to adsorb B(a)P is partly affected by the differences in the origin of PM2.5.

19.
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi ; 34(10): 1305-1312, 2020 Oct 15.
Artigo em Chinês | MEDLINE | ID: mdl-33063498

RESUMO

Objective: To explored the effect of stromal cell-derived factor 1α (SDF-1α) on promoting the migration ability of rat adipose derived stem cells (rADSCs) by constructed the rADSCs overexpression SDF-1α via adenovirus transfection. Methods: rADSCs were isolated from adipose tissue of 6-week-old SPF Sprague Dawley rats. Morphological observation, multi-directional differentiations (osteogenic, adipogenic, and chondrogenic inductions), and flow cytometry identification were performed. Transwell cell migration experiment was used to observe and screen the optimal concentration of exogenous SDF-1α to optimize the migration ability of rADSCs; the optimal multiplicity of infection (MOI) of rADSCs was screened by observing the cell status and fluorescence expression after transfection. Then the third generation of rADSCs were divided into 4 groups: group A was pure rADSCs; group B was rADSCs co-cultured with SDF-1α at the best concentration; group C was rADSCs infected with recombinant adenovirus-mediated green fluorescent protein (Adv-GFP) with the best MOI; group D was rADSCs infected with Adv-GFP-SDF-1α overexpression adenovirus with the best MOI. Cell counting kit 8 (CCK-8) and Transwell cell migration experiment were preformed to detect and compare the effect of exogenous SDF-1α and SDF-1α overexpression on the proliferation and migration ability of rADSCs. Results: The cell morphology, multi-directional differentiations, and flow cytometry identification showed that the cultured cells were rADSCs. After screening, the optimal stimulating concentration of exogenous SDF-1α was 12.5 nmol/L; the optimal MOI of Adv-GFP adenovirus was 200; the optimal MOI of Adv-GFP-SDF-1α overexpression adenovirus was 400. CCK-8 method and Transwell cell migration experiment showed that compared with groups A and C, groups B and D could significantly improve the proliferation and migration of rADSCs ( P<0.05); the effect of group D on enhancing the migration of rADSCs was weaker than that of group B, but the effect of promoting the proliferation of rADSCs was stronger than that of group D ( P<0.05). Conclusion: SDF-1α overexpression modification on rADSCs can significantly promote the proliferation and migration ability, which may be a potential method to optimize the application of ADSCs in tissue regeneration and wound repair.


Assuntos
Adipócitos , Quimiocina CXCL12 , Animais , Ratos , Ratos Sprague-Dawley , Células-Tronco , Células Estromais
20.
Cancers (Basel) ; 12(10)2020 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-33065994

RESUMO

Cetuximab, an IgG1 EGFR-directed antibody, promotes antibody-dependent cell-mediated cytotoxicity. We hypothesized that single-nucleotide polymorphisms (SNPs) in immune regulatory pathways may predict outcomes in patients with metastatic colorectal cancer treated with cetuximab-based regimens. A total of 924 patients were included: 105 received cetuximab in IMCL-0144 and cetuximab/irinotecan in GONO-ASL608LIOM01 (training cohort), 225 FOLFIRI/cetuximab in FIRE-3 (validation cohort 1), 74 oxaliplatin/cetuximab regimens in JACCRO CC-05/06 (validation cohort 2), and 520 FOLFIRI/bevacizumab in FIRE-3 and TRIBE (control cohorts). Twelve SNPs in five genes (IDO1; PD-L1; PD-1; CTLA-4; CD24) were evaluated by PCR-based direct sequencing. We analyzed associations between genotype and clinical outcomes. In the training cohort; patients with the CD24 rs52812045 A/A genotype had a significantly shorter median PFS and OS than those with the G/G genotype (PFS 1.3 vs. 3.6 months; OS 2.3 vs. 7.8 months) in univariate (PFS HR 3.62; p = 0.001; OS HR 3.27; p = 0.0004) and multivariate (PFS HR 3.18; p = 0.009; OS HR 4.93; p = 0.001) analyses. Similarly; any A allele carriers in the JACCRO validation cohort had a significantly shorter PFS than G/G carriers (9.2 vs. 11.8 months; univariate HR 1.90; p = 0.011; multivariate HR 2.12; p = 0.018). These associations were not demonstrated in the control cohorts. CD24 genetic variants may help select patients with metastatic colorectal cancer most likely to benefit from cetuximab-based therapy.

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