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1.
Org Lett ; 2021 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-34787425

RESUMO

The first palladium-catalyzed direct o-C-H iodination of benzaldehydes was successfully developed with the assistance of commercially available 2,5-bis(trifluoromethyl)aniline as the optimal monodentate transient directing group (MonoTDG). Moderate to excellent yields and good selectivity were achieved for a broad substrate scope under mild conditions. More importantly, the synthetic application was demonstrated by a concise two-step total synthesis of the natural product hernandial, which was accomplished by merging this new MonoTDG-assisted C-H iodination and subsequent copper-catalyzed cross-coupling.

2.
Cancer Cell Int ; 21(1): 592, 2021 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-34736474

RESUMO

BACKGROUND: As an important component of the Hippo pathway, WW domain-containing transcription regulator 1 (TAZ), is a transcriptional coactivator that is responsible for the progression of various types of cancers. Programmed cell death protein 1 (PD-1) receptors in activated T cells and their ligand programming death force 1 (PD-L1) are the main checkpoint signals that control T cell activity. Studies have shown high levels of PD-L1 in various cancers and that PD-L1/PD-1 signals to evade T-cell immunity. Recent data have demonstrated that TAZ can regulate the characteristics of cancer cells via PD-L1. Cervical cancer is a common gynecological disease worldwide. In this study, we attempted to evaluate the effects of TAZ and PD-L1 on cervical cancer. METHODS: Hela cervical cancer cells were transfected with TAZ plasmid or TAZ siRNA or PD-L1 siRNA by using Lipofectamine 2000. The relationship between TAZ and PD-L1 in cervical cancer cells was determined by qRT-PCR and western blotting. The functional roles of TAZ were confirmed via CCK-8, Transwell and flow cytometry assays. Western blotting was utilized to observe the expression of BCL-2 and Caspase-3. The clinicopathological correlation of TAZ and PD-L1 was evaluated via relevant databases. RESULT: TAZ is upregulated in cervical cancer and induces the growth and metastasis of cervical cancer cells by targeting PD-L1and inhibiting the ratio of apoptotic of cancer cells. High TAZ and PD-L1 expression was observed in different stage, grade, histological patterns, and ages of cervical cancer groups compared with normal cervix groups. Furthermore, high TAZ expression was positively correlated with the infiltration levels of immune cells and the expression of PD-L1.

3.
J Cereb Blood Flow Metab ; : 271678X211056393, 2021 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-34743630

RESUMO

Oxygen extraction fraction (OEF) and cerebral metabolic rate of oxygen (CMRO2) are markers of cerebral oxygen homeostasis and metabolism that may offer insights into abnormal changes in brain aging. The present study cross-sectionally related OEF and CMRO2 to cognitive performance and structural neuroimaging variables among older adults (n = 246, 74 ± 7 years, 37% female) and tested whether apolipoprotein E (APOE)-ε4 status modified these associations. Main effects of OEF and CMRO2 were null (p-values >0.06), and OEF interactions with APOE-ε4 status on cognitive and structural imaging outcomes were null (p-values >0.06). However, CMRO2 interacted with APOE-ε4 status on language (p = 0.002), executive function (p = 0.03), visuospatial (p = 0.005), and episodic memory performances (p = 0.03), and on hippocampal (p = 0.006) and inferior lateral ventricle volumes (p = 0.02). In stratified analyses, lower oxygen metabolism related to worse language (p = 0.02) and episodic memory performance (p = 0.03) among APOE-ε4 carriers only. Associations between CMRO2 and cognitive performance were primarily driven by APOE-ε4 carriers with existing cognitive impairment. Congruence across language and episodic memory results as well as hippocampal and inferior lateral ventricle volume findings suggest that APOE-ε4 may interact with cerebral oxygen metabolism in the pathogenesis of Alzheimer's disease and related neurodegeneration.

4.
Int J Hyperthermia ; 38(1): 1571-1583, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34724862

RESUMO

OBJECTIVE: To examine the effectiveness and safety of thermal ablative methods and myomectomy for the treatment of uterine fibroids. MATERIALS AND METHODS: We searched EMBASE, PubMed, the Cochrane Central Register of Controlled Trials, Scopus, CINAHL, ClinicalTrials.gov and Web of Science databases through April 2021. Clinical trials comparing the thermal ablative methods and myomectomy for the treatment of uterine fibroids were included. RESULTS: Thirteen studies including 4205 patients were eligible. The thermal ablative treatment group was associated with less major adverse events (only ultrasound guided high-intensity focused ultrasound) (RR, 0.111 [95% CI, 0.070-0.175], p=.0), shorter duration of hospital stays in observational studies (-0.1497 day, [95% CI, -1.593 to -0.321], p=.0) and in randomized controlled trials (RCTs) (-0.844 day, [95% CI, -0.1.142 to -0.546], p=.0), higher uterine fibroid symptom (UFS) score after operation (0.252 [95% CI, 0.165-0.339]; p=.0), transformed symptom severity (tSS) score after operation (0.515 [95% CI, 0.355-0.674]; p=.0) and quality of life (QoL) score after operation (0.188 [95% CI, 0.093-0.283]; p=.0) in comparison with myomectomy group. No statistically significant difference was found between the thermal ablative treatment group and myomectomy group with respect to reintervention rate and pregnancy rate. CONCLUSION: The current data available demonstrate that thermal ablative methods were not inferior to myomectomy in the treatment of uterine fibroids. The findings in this study need to be further confirmed by large RCTs.


Assuntos
Leiomioma , Miomectomia Uterina , Neoplasias Uterinas , Feminino , Humanos , Leiomioma/cirurgia , Gravidez , Neoplasias Uterinas/cirurgia
6.
Front Genet ; 12: 748111, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34737766

RESUMO

Cleidocranial dysplasia (CCD) is an autosomal dominant inheritable skeletal disorder characterized by cranial dysplasia, clavicle hypoplasia, and dental abnormalities. Mutations involving Runt-related transcription factor 2 (RUNX2) are currently the only known molecular etiology for CCD but are not identified in all CCD patients. No RUNX2 abnormality can be detected in about 20-30% of patients, and the molecular cause remains unknown. The present study includes a family case with typical features of CCD. RUNX2 mutation was first screened by sequencing analysis, and no mutation was detected. Copy number alterations of the RUNX2 gene were then measured by quantitative PCR and multiplex ligation-dependent probe amplification (MLPA). No copy number variation in RUNX2 could be detected. We performed whole-exome sequencing (WES) to identify the underlying genetic mutations. Unexpectedly, no abnormalities could be detected in genes related to the RUNX2 signaling pathway. Therefore, it was supposed that other new unknown gene variations might contribute to the CCD phenotype. We focused on Immunoglobulin superfamily member 10 (IGSF10), a gene related to bone development. An IGSF10 frameshift mutation (c.6001_6002delCT, p.Leu2001Valfs*24) was detected by WES. Sanger sequencing verified that this mutation was only detected in the patient and her affected mother but not in her unaffected father. Bioinformatics studies demonstrated that this mutation could change the 3D structure of the IGSF10 protein and severely damage its function. In addition, alkaline phosphatase (ALP) activity and the ability to form mineralized nodules were inhibited by IGSF10 knockdown compared with normal controls. The expression of bone sialoprotein (BSP) was significantly reduced by IGSF10 knockdown, but not that of other osteogenic markers. Our results provide new genetic evidence that IGSF10 mutation might contribute to CCD.

7.
Front Pharmacol ; 12: 758792, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34744738

RESUMO

Hyperglycemia-induced endothelial cell senescence has been widely reported to be involved in the pathogenesis of type 2 diabetes mellitus‒accelerated atherosclerosis. Thus, understanding the underlying mechanisms and identifying potential therapeutic targets for endothelial cell senescence are valuable for attenuating atherosclerosis progression. C1q/tumor necrosis factor-related protein 9 (CTRP9), an emerging potential cardiokine, exerts a significant protective effect with respect to atherosclerosis, particularly in endothelial cells. However, the exact mechanism by which CTRP9 prevents endothelial cells from hyperglycemia-induced senescence remains unclear. This study aimed to investigate the effects of CTRP9 on hyperglycemia-induced endothelial cell senescence and atherosclerotic plaque formation in diabetic apolipoprotein E knockout (ApoE KO) mice. Human umbilical vein endothelial cells (HUVECs) were cultured in normal glucose (5.5 mM) and high glucose (40 mM) with or without recombinant human CTRP9 protein (3 µg/ml) for 48 h. Purified lentiviruses overexpressing CTRP9 (Lv-CTRP9) and control vectors containing green fluorescent protein (Lv-GFP) were injected via the tail vein into streptozotocin-induced diabetic ApoE KO mice. Results revealed that exposure of HUVECs to HG significantly increased the expression of Krüppel-like factor 4 (KLF4) and cyclin-dependent kinase inhibitor p21 (p21) and decreased that of telomerase reverse transcriptase (TERT). Treatment with recombinant human CTRP9 protein protected HUVECs from HG-induced premature senescence and dysfunction. CTRP9 promoted the phosphorylation of AMP-activated kinase (AMPK), attenuated the expression of KLF4 and p21 induced by HG, and increased the expression of TERT in HUVECs. Furthermore, in the background of AMPKα knockdown or KLF4 activation, the protective effects of CTRP9 were abolished. In-vivo experiments showed that the overexpression of CTRP9 inhibited vascular senescence and reduced atherosclerotic plaque formation in ApoE KO mice with diabetes. In conclusion, we demonstrate that KLF4 upregulation plays a crucial role in HG-induced endothelial senescence. This anti-atherosclerotic effect of CTRP9 may be partly attributed to the inhibition of HG-induced endothelial senescence through an AMPKα/KLF4-dependent mechanism, suggesting that CTRP9 could benefit further therapeutic approaches for type 2 diabetes mellitus‒accelerated atherosclerosis.

8.
Pak J Pharm Sci ; 34(3(Special)): 1233-1241, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-34602394

RESUMO

To reveal the protective effect of Terminalia chebula Retz (TCR) on cardiotoxicity induced by radix of Aconitum kusnezoffii Reichb (AKR). Control, AKR, AKR-TCR 1:3, AKR-TCR 1:1, AKR-TCR 3:1 and TCR-prepared AKR groups were set up. After treatment, the heart tissues were observed by H&E staining and transmission electron microscope. Serum myoglobin (MB) and troponin (cTn) were detected by ELISA. UPLC-Q Exactive/MS analysis was performed to detect the metabolic difference among the groups. ELISA results showed that the MB and cTn values of AKR group were significantly higher than Control group (P<0.05), while those of the other groups were lower than AKR group. TCR-prepared AKR group had similar MB and cTn contents to the Control group. Histopathological examination also indicated better detoxifying effects in the TCR-prepared AKR and AKR-TCR 1:1 group. The serum metabolomics analysis showed obvious distinction between the AKR and Control groups, while AKR-TCR combination reversed the metabolomics changes induced by AKR. Through multivariate statistical analysis, 9 metabolic markers related to energy, nucleic acid and amino acid metabolism were identified. Conclusively, AKR-induced cardiotoxicity may be related to energy, nucleic acid and amino acid metabolism, and TCR can reduce the cardiotoxicity by regulating the relative metabolism pathways.

9.
Hum Vaccin Immunother ; : 1-7, 2021 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-34623932

RESUMO

Although measles, rubella and mumps elimination had achieved great progress in recent years, outbreaks were still reported worldwide. Serological surveillance on the remaining susceptibility in the population is essential to evaluate the preventive policy, estimate the current risk of infection, and predict evolutions in the future. In this study, we aimed to investigate the prevalence of seropositivity of antibodies against measles, rubella and mumps in a population of all ages in Youyang, southwest China. A cross-sectional hospital-based study was conducted among 657 cases who attended to Youyang Hospital from Sep 2018 to Aug 2019. Sero IgG antibodies were measured by ELISA. No difference in the seropositivity of antibodies against measles, rubella and mumps was found between neither urban vs. rural, nor male vs. female. The overall seropositivity of anti-measles, rubella, mumps IgG antibodies was 81.1% (95% CI: 78.0-83.9), 65.9% (95% CI: 62.2-69.4) and 63.2% (95% CI: 59.4-66.8), respectively. The IgG seropositivity varied with age significantly. In this study, the seropositivity of antibodies against measles, rubella and mumps among the participants was insufficient in the population, especially among infants, teenagers and productive women, who were suggested to booster the immunity. To better control and eliminate measles, mumps and rubella-related diseases, nation-wide active laboratory-supported surveillance, outbreak investigation and revaccination for vulnerable population are needed.

10.
Exp Ther Med ; 22(5): 1318, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34630672

RESUMO

The aim of the present study was to investigate the expression and role of microRNA-18a-5p (miR-18a-5p) during the formation of hypertrophic scar (HS), and to further explore the molecular mechanisms involved. Downregulation of miR-18a-5p in HS tissues and human HS fibroblasts (hHSFs) was detected by reverse transcription-quantitative polymerase chain reaction. The binding sites between miR-18a-5p and the 3'-untranslated region of SMAD family member 2 (Smad2) were predicted by TargetScan and confirmed by dual-luciferase reporter assay. To investigate the role of miR-18a-5p in HS formation, the effects of miR-18a-5p downregulation or upregulation on hHSFs were subsequently determined. Cell proliferation was detected by an MTT assay, while cell apoptosis was measured by flow cytometry. In addition, the protein expression levels of Smad2, Collagen I (Col I) and Col III were examined by western blot assay. The findings indicated that miR-18a-5p downregulation in hHSFs significantly promoted the cell proliferation, decreased cell apoptosis and enhanced the expression levels of Smad2, Col I and Col III protein and mRNA, whereas miR-18a-5p upregulation in hHSFs exerted opposite effects. Notably, the effects of miR-18a-5p upregulation on hHSFs were eliminated by Smad2 upregulation. In conclusion, the data indicated that miR-18a-5p was downregulated during HS formation, and its upregulation repressed scar fibroblast proliferation and extracellular matrix deposition by targeting Smad2. Therefore, miR-18a-5p may serve as a novel therapeutic target for the treatment of HS.

11.
Stroke ; : STROKEAHA121034349, 2021 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-34702069

RESUMO

BACKGROUND AND PURPOSE: Left ventricular (LV) mass index is a marker of subclinical LV remodeling that relates to white matter damage in aging, but molecular pathways underlying this association are unknown. This study assessed if LV mass index related to cerebrospinal fluid (CSF) biomarkers of microglial activation (sTREM2 [soluble triggering receptor expressed on myeloid cells 2]), axonal injury (NFL [neurofilament light]), neurodegeneration (total-tau), and amyloid-ß, and whether these biomarkers partially accounted for associations between increased LV mass index and white matter damage. We hypothesized higher LV mass index would relate to greater CSF biomarker levels, and these pathologies would partially mediate associations with cerebral white matter microstructure. METHODS: Vanderbilt Memory and Aging Project participants who underwent cardiac magnetic resonance, lumbar puncture, and diffusion tensor imaging (n=142, 72±6 years, 37% mild cognitive impairment [MCI], 32% APOE-ε4 positive, LV mass index 51.4±8.1 g/m2, NFL 1070±588 pg/mL) were included. Linear regressions and voxel-wise analyses related LV mass index to each biomarker and diffusion tensor imaging metrics, respectively. Follow-up models assessed interactions with MCI and APOE-ε4. In models where LV mass index significantly related to a biomarker and white matter microstructure, we assessed if the biomarker mediated white matter associations. RESULTS: Among all participants, LV mass index was unrelated to CSF biomarkers (P>0.33). LV mass index interacted with MCI (P=0.01), such that higher LV mass index related to increased NFL among MCI participants. Associations were also present among APOE-ε4 carriers (P=0.02). NFL partially mediated up to 13% of the effect of increased LV mass index on white matter damage. CONCLUSIONS: Subclinical cardiovascular remodeling, measured as an increase in LV mass index, is associated with neuroaxonal degeneration among individuals with MCI and APOE-ɛ4. Neuroaxonal degeneration partially reflects associations between higher LV mass index and white matter damage. Findings highlight neuroaxonal degeneration, rather than amyloidosis or microglia, may be more relevant in pathways between structural cardiovascular remodeling and white matter damage.

12.
Clin Nutr ; 40(11): 5615-5618, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34656958

RESUMO

BACKGROUND & AIM: The association between habitual coffee or caffeine consumption and age at onset (AAO) of Huntington's disease (HD) is unclear. We employed Mendelian randomization to investigate the causal relationship between coffee consumption and AAO of HD. METHODS: The instrumental variable including 14 independent genetic variants associated with coffee consumption was selected from a genome-wide association study (GWAS) meta-analysis of 375,833 individuals of European ancestry. Genetic association estimates for AAO of HD were obtained from the Genetic Modifiers of Huntington's Disease Consortium GWAS meta-analysis including 9064 HD patients of European ancestry. The inverse variance weighted method was used to evaluate the causal estimate and a comprehensive set of analyses tested the robustness of our results. RESULTS: Genetically predicted higher coffee consumption was associated with an earlier AAO of HD (ß = -1.84 years, 95% confidence interval = -3.47 to -0.22, P = 0.026). Results were robust to potential pleiotropy and weak instrument bias. CONCLUSIONS: This genetic study suggests high coffee consumption is associated with an earlier AAO of HD. Coffee is widely consumed and thus our findings, if confirmed, offers a potential way to delay the onset of this debilitating autosomal dominant disease.

13.
Arterioscler Thromb Vasc Biol ; 41(12): 3015-3024, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34706559

RESUMO

OBJECTIVE: To determine whether baseline aortic stiffness, measured by aortic pulse wave velocity (PWV), relates to longitudinal cerebral gray or white matter changes among older adults. Baseline cardiac magnetic resonance imaging will be used to assess aortic PWV while brain magnetic resonance imaging will be used to assess gray matter and white matter hyperintensity (WMH) volumes at baseline, 18 months, 3 years, 5 years, and 7 years. Approach and Results: Aortic PWV (m/s) was quantified from cardiac magnetic resonance. Multimodal 3T brain magnetic resonance imaging included T1-weighted imaging for quantifying gray matter volumes and T2-weighted fluid-attenuated inversion recovery imaging for quantifying WMHs. Mixed-effects regression models related baseline aortic PWV to longitudinal gray matter volumes (total, frontal, parietal, temporal, occipital, hippocampal, and inferior lateral ventricle) and WMH volumes (total, frontal, parietal, temporal, and occipital) adjusting for age, sex, race/ethnicity, education, cognitive diagnosis, Framingham stroke risk profile, APOE (apolipoprotein E)-ε4 carrier status, and intracranial volume. Two hundred seventy-eight participants (73±7 years, 58% male, 87% self-identified as non-Hispanic White, 159 with normal cognition, and 119 with mild cognitive impairment) from the Vanderbilt Memory & Aging Project (n=335) were followed on average for 4.9±1.6 years with PWV measurements occurring from September 2012 to November 2014 and longitudinal brain magnetic resonance imaging measurements occurring from September 2012 to June 2021. Higher baseline aortic PWV was related to greater decrease in hippocampal (ß=-3.6 [mm3/y]/[m/s]; [95% CI, -7.2 to -0.02] P=0.049) and occipital lobe (ß=-34.2 [mm3/y]/[m/s]; [95% CI, -67.8 to -0.55] P=0.046) gray matter volume over time. Higher baseline aortic PWV was related to greater increase in WMH volume over time in the temporal lobe (ß=17.0 [mm3/y]/[m/s]; [95% CI, 7.2-26.9] P<0.001). All associations may be driven by outliers. CONCLUSIONS: In older adults, higher baseline aortic PWV related to greater decrease in gray matter volume and greater increase in WMHs over time. Because of unmet cerebral metabolic demands and microvascular remodeling, arterial stiffening may preferentially affect certain highly active brain regions like the temporal lobes. These same regions are affected early in the course of Alzheimer disease.

14.
Org Lett ; 23(21): 8402-8406, 2021 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-34664971

RESUMO

A unified method for direct C4-H halogenation of indoles has been accomplished with the assistance of anthranilic acids as suitable transient directing groups. Exclusive site selectivity (one out of five potential reactive sites) as well as good functional group tolerance was obtained to install three kinds of halogen atoms (Cl, Br and I, respectively) by using inexpensive N-halosuccinimides (NXS) as halogen sources under mild conditions. Taking advantage of the rich functional groups in the product, a diversity of nitrogen-containing heterocycles were facily constructed via one-step late-stage derivations.

15.
Int J Biol Macromol ; 192: 684-691, 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34648802

RESUMO

pH-sensitive hydrogels have been applied in delivering probiotics and drugs. However, pH sensitivity has been found to be contradictory with structural stability in hydrogel preparation. In this work, a novel strategy based on two systems of sodium carboxymethyl cellulose (CMC)/chitosan (CS) and sodium alginate (SA)/calcium chloride was designed to construct a reticulated shell structure stable for 3 h in simulated gastric fluid (pH 1.2) but began to break up at 2 h in simulated intestinal fluid (pH 6.8), exhibiting obvious pH sensitivity. The embedding rate of Bacillus subtilis natto reached to 67.3%, and the sustained release lasted for more than 10 h. It is implicated that the reticulated shell structure has harmoniously balanced the two incompatible properties of pH sensitivity and sustained release of CMC/CS/SA beads.

16.
Am J Otolaryngol ; 43(1): 103263, 2021 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-34653954

RESUMO

OBJECTIVES: During the COVID-19 pandemic, maintenance of safe and timely oncologic care has been challenging. The goal of this study is to compare presenting symptoms, staging, and treatment of head and neck mucosal squamous cell carcinoma during the pandemic with an analogous timeframe one year prior. MATERIALS AND METHODS: Retrospective cohort study at a single tertiary academic center of new adult patients evaluated in a head and neck surgical oncology clinic from March -July 2019 (pre-pandemic control) and March - July 2020 (COVID-19 pandemic). RESULTS: During the pandemic, the proportion of patients with newly diagnosed malignancies increased by 5%, while the overall number of new patients decreased (n = 575) compared to the control year (n = 776). For patients with mucosal squamous cell carcinoma (SCC), median time from referral to initial clinic visit decreased from 11 days (2019) to 8 days (2020) (p = 0.0031). There was no significant difference in total number (p = 0.914) or duration (p = 0.872) of symptoms. During the pandemic, patients were more likely to present with regional nodal metastases (adjusted odds ratio (OR) 2.846, 95% CI 1.072-3.219, p = 0.028) and more advanced clinical nodal (N) staging (p = 0.011). No significant difference was seen for clinical tumor (T) (p = 0.502) or metastasis (M) staging (p = 0.278). No significant difference in pathologic T (p = 0.665), or N staging (p = 0.907) was found between the two periods. CONCLUSION: Head and neck mucosal SCC patients presented with more advanced clinical nodal disease during the early months of the COVID-19 pandemic despite no change in presenting symptoms.

17.
Biochem Biophys Res Commun ; 581: 96-102, 2021 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-34662809

RESUMO

OBJECTIVE: To examine the mechanisms of Nogo-B (RTN4B) in the protection of blood-retinal barrier in experimental diabetic retinopathy. METHODS: The level of Nogo-B in vitreous and plasma samples was detected with ELISA. Diabetes was induced in Sprague-Dawley rats with intraperitoneal injection of streptozotocin. The rats were injected intravitreally with adeno-associated virus (AAV) for knockdown the expression of Nogo-B in retina or/and as AAV negative control. The permeability of blood-retinal barrier was detected with Rhodamine-B-dextran leakage assay. The expressions of Nogo-B, junctional proteins, inflammatory factors and signaling pathways were examined with Western blot and quantitative real-time PCR. RESULTS: Nogo-B expression was significantly upregulated in clinical samples and experimental diabetic rat models. Under normal condition, Nogo-B knockdown resulted in the increased permeability of retinal blood vessels. In diabetic rat retinas, the vascular leakage was increased significantly, which was partially decreased by Nogo-B knockdown through increasing p/t-Src (Tyr529) and p/t-Akt (Ser473), and decreasing p/t-ERK1/2. CONCLUSION: Nogo-B was increased in diabetic retinopathy and silencing Nogo-B is a promising therapy for diabetic retinopathy.

18.
ACS Biomater Sci Eng ; 7(11): 5154-5164, 2021 11 08.
Artigo em Inglês | MEDLINE | ID: mdl-34636537

RESUMO

Photothermal therapy (PTT) using nanoparticles is one of the research hotspots in the field of cancer therapy. However, the thermal resistance of tumor cells and the elimination of nanoparticles by the body's immune system reduce their therapeutic effect. Therefore, it is essential to reduce heat resistance, improve their biocompatibility, and reduce the clearance of the immune system. In this work, we constructed a biomimetic platform for cancer therapy based on heat shock protein (HSP) inhibitors, 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG))-loaded and platelet membrane (PM)-coated mesoporous platinum nanoparticles (MPNPs). First, MPNPs with the properties of chemotherapy and PTT were synthesized to load 17-DMAG (17-DMAG/MPNPs). Then, they were coated with PM for tumor targeting and improved biocompatibility to obtain the final bionic nanotherapy platform 17-DMAG/MPNPs@PM. The results in vivo and in vitro showed that 17-DMAG/MPNPs@PM could accumulate in the tumor and effectively inhibit the growth of tumor cells. Therefore, the biomimetic nanotherapy system is expected to provide new ideas for cancer treatment.


Assuntos
Antineoplásicos , Nanopartículas Metálicas , Neoplasias , Antineoplásicos/uso terapêutico , Biomimética , Humanos , Neoplasias/tratamento farmacológico , Platina
19.
Surg Oncol ; 39: 101666, 2021 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-34634575

RESUMO

Thyroglobulin (Tg) measurement in fine-needle aspiration (FNA-Tg) has proved to be an excellent tool to identify metastatic cervical lymph nodes (CLN) before or after surgery for papillary thyroid cancer (PTC). The diagnostic value of FNA-Tg for metastatic CLN in PTC patients is higher than that of ultrasound (US) and fine-needle aspiration cytology (FNAC), especially for small or cystic LN. The combination of FNAC and FNA-Tg can provide nearly 100% diagnostic sensitivity and specificity for CLN metastasis. However, the cutoff values of FNA-Tg for metastatic CLN have not been standardized, and the reported cutoff values of FNA-Tg range from 0.2 ng/ml to 77 ng/ml because of the differences in study samples, Tg measurement methods, Tg assays kits, etc. Serum anti-thyroglobulin antibody level, serum thyroglobulin level, the presence or absence of thyroid glands, and the characteristics of CLN may be factors affecting the accuracy of FNA-Tg. This review summarizes the recent research on the application of FNA-Tg in the diagnosis of metastatic LN in PTC and provides a reliable basis for the clinical diagnosis of cervical lymph node metastasis.

20.
J Agric Food Chem ; 69(38): 11461-11469, 2021 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-34542274

RESUMO

Our previous study showed that ochratoxin A (OTA), one of the most common mycotoxins in feed, could induce immunosuppression with long-time exposure but immunostimulation with short-time exposure. However, limited studies for the control of OTA-induced two-way immune toxicity were carried out. This study explored the effects of mannan oligosaccharide (MOS), a glucomannoprotein complex with immunoregulatory capability derived from the yeast cell wall, on OTA-induced immune toxicity and its underlying mechanisms. Surprisingly, the results showed that MOS significantly attenuated immunosuppression induced by long-time OTA treatment but did not provide protection against immunostimulation induced by short-time OTA treatment on porcine alveolar macrophages (PAMs), as demonstrated by the expressions of inflammatory cytokines and the capability of migration and phagocytosis. Further, MOS increased the OTA-inhibited autophagy level and the JNK phosphorylation level on PAMs with long-time OTA treatment. In addition, the inhibition of autophagy by 3-MA or the inhibition of JNK phosphorylation by SP600125 could partly block the protective effects of MOS on OTA-induced immunosuppression. Importantly, the inhibition of JNK phosphorylation down-regulated the MOS-promoted autophagy level. In conclusion, MOS could attenuate OTA-induced immunosuppression with short-time exposure on PAMs through activating JNK-mediated autophagy but had no significant effects on OTA-induced immunostimulation with short-time exposure. Our study provides new insights into the application of MOS as an immunoregulator against mycotoxin-induced immune toxicity.


Assuntos
Mananas , Ocratoxinas , Animais , Linhagem Celular , Imunização , Imunossupressão , Ocratoxinas/toxicidade , Oligossacarídeos , Suínos
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