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1.
Ann Vasc Surg ; 2021 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-33831523

RESUMO

AIM: Aortic intimo-intimal intussusception (AoII) is a rare manifestation of aortic dissection with high mortality. This study aimed to obtain a comprehensive understanding of AoII. METHODS: Three databases (Pubmed, Scopus, Embase) were searched with predefined search terms ["intimal intussusception", "aortic intussusception", "(circumferential) AND (intimal dissection)" and "(circumferential) AND (aortic dissection)"]. Demographics, clinical manifestations, imaging methods, therapies, and follow-up data were recorded and analyzed. RESULTS: The literature search finally identified 81 papers comprising 87 patients (Mean age: 53.7±14.9 years old; male: n=63). According to morphologic criteria (orientation of AoII intimal flap), patients were divided into three groups: antegrade(n=37), retrograde (n=49) and bidirectional (n=1) orientation. The most frequent symptoms in antegrade group were chest pain (62.2%), syncope (27%), and unconsciousness (21.6%), while in retrograde group, they were chest pain (71.4%), dyspnea (20.4%), and back pain (16.3%). Regarding applied imaging modalities, 67.5% of patients in antegrade group were diagnosed with≥2 methods, comparing with 87.7% in retrograde group. A total of 21 patients (24.1%) with AoII finally died, among which 13.8% (12/87) died before surgery. CONCLUSION: AoII is a rare form of aortic dissection with high mortality. Antegrade orientation of the intima flap was more accompanied with neurological disorders and asymmetric blood pressure, while retrograde orientation mostly manifested with aortic regurgitation. Application of multiple imaging examinations may detect this rare entity in time.

2.
Colloids Surf B Biointerfaces ; 202: 111658, 2021 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-33677134

RESUMO

TiO2 acts as an inorganic sunscreen and photocatalyst to protect humans from environmental pollutants. We incorporated TiO2 into mesoporous silica (SBA-15) for skin application to prevent environmental stresses including UVA irradiation and pollutant invasion. Organic ultraviolet (UV)A filters such as avobenzone and oxybenzone were then loaded into mesoporous support for synergistic sunscreen efficiency. The as-prepared formulations with different TiO2 amounts (10 %-50 %) were fabricated. The pore size decreased from 4.72 to 4.00 nm following the increase in TiO2 percentage. TiO2/SBA-15 captured about 60 % fluoranthene and 80 % furfural within 3 h with no significant difference due to different TiO2 content. The in vitro photoprotection assessed by UVA/UVB ratio exhibited the increase in Boots star rating from 2 to 3 to 5 by entrapment of avobenzone into TiO2/SBA-15. Thirty-percent TiO2/SBA-15 in hydrogel decreased avobenzone and oxybenzone deposition by 70 % and 80 % compared to free form, respectively. Avobenzone and TiO2 supplementation to SBA-15 significantly alleviated skin cell death and neutrophil recruitment in the photoaged mouse skin compared to the SBA-15 application alone. Compared to the UVA-irradiated skin, 30 % TiO2/SBA-15 showed a 2.5- and 3.1-fold decline in IL-1ß and IL-6 levels, respectively. The TiO2/SBA-15 hybrid was considered non-irritant based on results of cytotoxicity assay, skin histology, and cutaneous barrier function. Our data indicate that the versatile mesoporous silica is an effective system for topical use in sunscreen and skin protection.

3.
Redox Biol ; 38: 101813, 2020 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-33279869

RESUMO

Diabetic kidney disease is known as a major cause of chronic kidney disease and end stage renal disease. Polysulfides, a class of chemical agents with a chain of sulfur atoms, are found to confer renal protective effects in acute kidney injury. However, whether a polysulfide donor, sodium tetrasulfide (Na2S4), confers protective effects against diabetic nephropathy remains unclear. Our results showed that Na2S4 treatment ameliorated renal dysfunctional and histological damage in diabetic kidneys through inhibiting the overproduction of inflammation cytokine and reactive oxygen species (ROS), as well as attenuating renal fibrosis and renal cell apoptosis. Additionally, the upregulated phosphorylation and acetylation levels of p65 nuclear factor κB (p65 NF-κB) and signal transducer and activator of transcription 3 (STAT3) in diabetic nephropathy were abrogated by Na2S4 in a sirtuin-1 (SIRT1)-dependent manner. In renal tubular epithelial cells, Na2S4 directly sulfhydrated SIRT1 at two conserved CXXC domains (Cys371/374; Cys395/398), then induced dephosphorylation and deacetylation of its targeted proteins including p65 NF-κB and STAT3, thereby reducing high glucose (HG)-caused oxidative stress, cell apoptosis, inflammation response and epithelial-to-mesenchymal transition (EMT) progression. Most importantly, inactivation of SIRT1 by a specific inhibitor EX-527, small interfering RNA (siRNA), a de-sulfhydration reagent dithiothreitol (DTT), or mutation of Cys371/374 and Cys395/398 sites at SIRT1 abolished the protective effects of Na2S4 on diabetic kidney insulting. These results reveal that polysulfides may attenuate diabetic renal lesions via inactivation of p65 NF-κB and STAT3 phosphorylation/acetylation through sulfhydrating SIRT1.

4.
Int J Mol Sci ; 21(20)2020 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-33096924

RESUMO

Cisplatin, a widely used chemotherapy for the treatment of various tumors, is clinically limited due to its extensive nephrotoxicity. Inflammatory response in tubular cells is a driving force for cisplatin-induced nephrotoxicity. The plant-derived agents are widely used to relieve cisplatin-induced renal dysfunction in preclinical studies. Polysulfide and hydrogen sulfide (H2S) are ubiquitously expressed in garlic, and both of them are documented as potential agents for preventing and treating inflammatory disorders. This study was designed to determine whether polysulfide and H2S could attenuate cisplatin nephrotoxicity through suppression of inflammatory factors. In renal proximal tubular cells, we found that sodium tetrasulfide (Na2S4), a polysulfide donor, and sodium hydrosulfide (NaHS) and GYY4137, two H2S donors, ameliorated cisplatin-caused renal toxicity through suppression of the massive production of inflammatory cytokines, including tumor necrosis factor α (TNF-α), interleukin-1ß (IL-1ß), interleukin-6 (IL-6), and cyclooxygenase-2 (COX-2). Mechanistically, the anti-inflammatory actions of Na2S4 and H2S may be mediated by persulfidation of signal transducer and activator of transcription 3 (STAT3) and inhibitor kappa B kinase ß (IKKß), followed by decreased phosphorylation of STAT3 and IKKß. Moreover, the nuclear translocation of nuclear transcription factor kappa B (NF-κB), and phosphorylation and degradation of nuclear factor kappa B inhibitor protein alpha (IκBα) induced by cisplatin, were also mitigated by both polysulfide and H2S. In mice, after treatment with polysulfide and H2S donors, cisplatin-associated renal dysfunction was strikingly ameliorated, as evidenced by measurement of serum blood urea nitrogen (BUN) and creatinine levels, renal morphology, and the expression of renal inflammatory factors. Our present work suggests that polysulfide and H2S could afford protection against cisplatin nephrotoxicity, possibly via persulfidating STAT3 and IKKß and inhibiting NF-κB-mediated inflammatory cascade. Our results might shed light on the potential benefits of garlic-derived polysulfide and H2S in chemotherapy-induced renal damage.

5.
Huan Jing Ke Xue ; 41(9): 4180-4196, 2020 Sep 08.
Artigo em Chinês | MEDLINE | ID: mdl-33124300

RESUMO

In this study, 130 surface soil samples were collected at an industrial pollution site in Beijing and the contents of As, Be, Cd, Cu, Cr, Hg, Ni, Pb, Sb, Ti, Zn, and 16 PAHs were determined. The positive matrix factorization (PMF) model was used to analyze the sources of heavy metals and PAHs, and the contributions of these sources to carcinogenic risk and hazard index in the study area were calculated. The results showed that the contents of Cd, Cu, Pb, Hg, As, Zn, and Cr in the soil exceeded the background values in different degrees; Cd, Hg, Pb, Zn, and Cu exceeded the background values by>50%. Low molecular weight PAHs (two and three rings) and high molecular weight PAHs (four to six rings) accounted for 39.6% and 60.4% of the total content of 16 PAHs. The PAH content at 77% of the sampling points at the target site was more than 1000 µg ·kg-1, which suggests severe PAH pollution at the site. Heavy metals Be, Ti, As, and Ni mainly originated from natural sources. There are three major sources of 7 heavy metals and 16 PAHs at the site: coal combustion (Hg and ∑16PAHs), smelting (Cu, Cr, Pb, and Zn), and traffic (Sb and Cd). The contribution rates of these sources to the total average contents of seven heavy metals and sixteen PAHs at 130 sampling sites were 8.46% (coal combustion), 90.61% (smelting), and 0.94% (traffic). Human health risk assessment results showed that the carcinogenic risk of seven heavy metals and ∑16PAHs ranged from 4.17×10-6 to 39.38×10-4, and the hazard index ranged from 0 to 32.23. The maximum carcinogenic risk and hazard index values were calculated near the coking plant. Benzo[α]pyrene was the PAH that posed the highest carcinogenic risk and Zn was the heavy metal that had the highest hazard index value. The average carcinogenic risk of coal combustion was 2.16×10-4, accounting for 50.26% of the total average carcinogenic risk. The average hazard index of smelting was 0.834, accounting for 56.43% of the total average non-carcinogenic risk. These two pollution sources are responsible for the high levels of heavy metals and PAHs in the soil of the steel smelting sites that pose the most severe health risks. The results of this study can provide reference for soil remediation and process optimization at other heavily polluted industrial sites.


Assuntos
Metais Pesados , Poluentes do Solo , Pequim , China , Monitoramento Ambiental , Humanos , Metais Pesados/análise , Medição de Risco , Solo , Poluentes do Solo/análise
6.
Artigo em Inglês | MEDLINE | ID: mdl-32904600

RESUMO

Objective: The aim of this network meta-analysis (NMA) was to explore the effectiveness of different traditional Chinese medicine injections (TCMIs) combined with systemic chemotherapy for the treatment of hepatocellular carcinoma (HCC). Methods: A comprehensive search for randomized controlled trials (RCTs) was performed with regard to different TCMIs for treating HCC in seven electronic databases up to November 2019. The quality assessment of the included RCTs was conducted according to the Cochrane risk of bias tool. The objective response rate (ORR), clinical benefit rate (CBR), and Karnofsky performance score (KPS) data were extracted. The network meta-analysis used the network package in Stata software to analyse the data and draw a map of the evidence summarizing the direct and indirect comparisons. Results: A total of 1697 articles were retrieved through the comprehensive search. Twenty RCTs focusing on Aidi injection, compound Kushen injection, and Kanglaite injection as adjuvant therapies to chemotherapy were included, involving a total of 1418 patients. The NMA statistics showed that all three indicators (ORR, CBR, and KPS) were better in the combined treatment group of TCMIs with chemotherapy than that in the single treatment group of chemotherapy alone. Kanglaite injection tended to be better than the other two in terms of primary outcome, but there was not a significant difference. The combined treatment group had fewer adverse reactions than the single treatment group. Moreover, several articles reported that TCMIs combined with chemotherapy could increase the number of CD3+ and CD4+ T lymphocytes and the ratio of CD4+/CD8+ T lymphocytes. Conclusions: TCMIs combined with systemic chemotherapy could be an effective and safe treatment option for patients with HCC. Kanglaite injection showed a tendency to be better than the other two kinds of injections in terms of ORR. Nevertheless, additional results from multicentre trials and high-quality studies will be pivotal for supporting our findings.

7.
Curr Neuropharmacol ; 2020 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-32888271

RESUMO

Hydrogen sulfide (H2S) and hydrogen polysulfides are recognized as important signaling molecules that are generated physiologically in the body, including the central nervous system (CNS). Studies have shown that these two molecules are involved in cytoprotection against oxidative stress and inflammatory response. In the brain system, H2S and polysulfides exert multiple functions in both health and diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), memory decline, and glioma. Mechanistically, S-Persulfidation (also known as S-sulfuration or S-sulfhydration) of target proteins is believed to be a fundamental mechanism that underlies H2S-regulated signaling pathways. Cysteine S-Persulfidation is an important paradigm of post-translational protein modification in the process of H2S signaling. This model is established as a critical redox mechanism to regulate numerous biological functions, especially in H2S-mediated neuroprotection and neurogenesis. Although the current research of S-Persulfidation is still in its infancy, accumulative evidence suggests that protein S-Persulfidation may share similar characteristics with protein S-nitrosylation. In this review, we will provide a comprehensive insight into the S-Persulfidation biology of H2S and polysulfides in neurological ailments and presume potential avenues for therapeutic development in these disorders based on S-Persulfidation of target proteins.

8.
Theranostics ; 10(14): 6149-6166, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32483445

RESUMO

Reduced hepatic Na+/K+-ATPase (NKA) activity and NKAα1 expression are engaged in the pathologies of metabolism diseases. The present study was designed to investigate the potential roles of NKAα1 in hepatic gluconeogenesis and glycogenesis in both hepatocytes and obese diabetic mice. Methods: Insulin resistance was mimicked by glucosamine (GlcN) in either human hepatocellular carcinoma (HepG2) cells or primary mouse primary hepatocytes. Obese diabetic mice were induced by high-fat diet (HFD) feeding for 12 weeks. Results: We found that both NKA activity and NKAα1 protein level were downregulated in GlcN-treated hepatocytes and in the livers of obese diabetic mice. Pharmacological inhibition of NKA with ouabain worsened, while activation of NKAα1 with an antibody against an extracellular DR region of NKAα1 subunit (DR-Ab) prevented GlcN-induced increase in gluconeogenesis and decrease in glycogenesis. Likewise, the above results were also corroborated by the opposite effects of genetic knockout/overexpression of NKAα1 on both gluconeogenesis and glycogenesis. In obese diabetic mice, hepatic activation or overexpression of NKAα1 stimulated the PI3K/Akt pathway to suppress hyperglycemia and improve insulin resistance. More importantly, loss of NKA activities in NKAα1+/- mice was associated with more susceptibility to insulin resistance following HFD feeding. Conclusions: Our findings suggest that NKAα1 is a physiological regulator of glucose homoeostasis and its DR-region is a novel target to treat hepatic insulin resistance.

9.
Pharmacol Res ; 159: 104961, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32474086

RESUMO

Cardiovascular diseases are recognized to be a major cause of people morbidity and mortality. A host of stress signals contribute to the pathogenesis of cardiovascular disorders. Deficiency of hydrogen sulfide (H2S) or nitric oxide (NO) coordinately plays essential roles in the development of cardiovascular diseases. Recent studies have shown that interaction between the two gaseostransmitters, H2S and NO, may give rise to nitroxyl (HNO), one-electron-reduced product of NO. HNO is found to exhibit a variety of biological and pharmacological properties including positive inotropy and cardiovascular protective effects, etc. In this review, recent progresses regarding HNO generation, detection, biochemical and pharmacological functions are discussed.

10.
Acad Radiol ; 2020 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-32111466

RESUMO

RATIONALE AND OBJECTIVES: The purpose of this study was to define the CT spectral imaging characteristics of pancreatic neuroendocrine neoplasms (PNENs) and evaluate their potential for differential diagnosis of nonlow grade (non-LG) PNENs from low grade (LG) PNENs. MATERIALS AND METHODS: CT spectral imaging data of 54 pathologically proven PNENs were retrospectively reviewed. Patients were divided into two groups: 40 cases with grade 1 in LG PNENs group and 14 cases with grade 2 and grade 3 in non-LG PNENs group. RESULTS: Gender, calcification, inhomogeneity, invasiveness, PD dilatation, lymph node enlargement, size, normalized iodine (water) concentration in arterial phase (AP) (Iodine (ap)), normalized effective-Z (Zap), slope of normalized CT spectral curves in both AP, and portal venous phase were found to be significant variables for differentiating non-LG PNENs from LG PNENs (p < 0.05). Non-LG PNENs had larger size and lower Zap and Iodine (ap) than LG PNENs. The tumor size, Zap and Iodine (ap) had fair to good diagnostic performance with the area under receiver-operating-characteristic curve (AUC) 0.843, 0.733, and 0.728, respectively. Multivariate analysis with logistic regression had higher AUC (p<0.05) than all the single parameters except for size. CONCLUSION: There were significant differences in CT spectral imaging parameters between non-LG and LG PNENs. Tumor size was the most promising independent parameter and the combination of quantitative parameters with qualitative parameters is the best predictor in differentiating of non-LG PNENs from LG PNENs. CT spectral imaging can help determine the malignancy of PNENs, which can better assist in surgical planning.

11.
Redox Biol ; 32: 101493, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32182574

RESUMO

Nitroxyl (HNO), one-electron reduced and protonated sibling of nitric oxide (NO), is a potential regulator of cardiovascular functions. It produces positive inotropic, lusitropic, myocardial anti-hypertrophic and vasodilator properties. Despite of these favorable actions, the significance and the possible mechanisms of HNO in diabetic hearts have yet to be fully elucidated. H9c2 cells or primary neonatal mouse cardiomyocytes were incubated with normal glucose (NG) or high glucose (HG). Male C57BL/6 mice received intraperitoneal injection of streptozotocin (STZ) to induce diabetes. Here, we demonstrated that the baseline fluorescence signals of HNO in H9c2 cells were reinforced by both HNO donor Angeli's salt (AS), and the mixture of hydrogen sulfide (H2S) donor sodium hydrogen sulfide (NaHS) and NO donor sodium nitroprusside (SNP), but decreased by HG. Pretreatment with AS significantly reduced HG-induced cell vitality injury, apoptosis, reactive oxygen species (ROS) generation, and hypertrophy in H9c2 cells. This effect was mediated by induction of caveolin-3 (Cav-3)/endothelial nitric oxide (NO) synthase (eNOS) complex. Disruption of Cav-3/eNOS by pharmacological manipulation or small interfering RNA (siRNA) abolished the protective effects of AS in HG-incubated H9c2 cells. In STZ-induced diabetic mice, administration of AS ameliorated the development of diabetic cardiomyopathy, as evidenced by improved cardiac function and reduced cardiac hypertrophy, apoptosis, oxidative stress and myocardial fibrosis without affecting hyperglycemia. This study shed light on how interaction of NO and H2S regulates cardiac pathology and provide new route to treat diabetic cardiomyopathy with HNO.

12.
Atherosclerosis ; 292: 112-118, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31785492

RESUMO

Aortic aneurysm (AA) is a complex and dangerous vascular disease, featuring progressive and irreversible vessel dilatation. AA is typically detected either by screening, or identified incidentally through imaging studies. To date, no effective pharmacological therapies have been identified for clinical AA management, and either endovascular repair or open surgery remains the only option capable of preventing aneurysm rupture. In recent years, multiple research groups have endeavored to both identify noncoding RNAs and to clarify their function in vascular diseases, including aneurysmal pathologies. Notably, the molecular roles of noncoding RNAs in AA development appear to vary significantly between thoracic aortic aneurysms (TAAs) and abdominal aortic aneurysms (AAAs). Some microRNAs (miRNA - a non-coding RNA subspecies) appear to contribute to AA pathophysiology, with some showing major potential for use as biomarkers or as therapeutic targets. Studies of long noncoding RNAs (lncRNAs) are more limited, and their specific contributions to disease development and progression largely remain unexplored. This review aims to summarize and discuss the most current data on lncRNAs and their mediation of AA pathophysiology.

13.
Antioxid Redox Signal ; 32(5): 331-349, 2020 02 10.
Artigo em Inglês | MEDLINE | ID: mdl-31617376

RESUMO

Significance: As one-electron reduced molecule of nitric oxide (NO), nitroxyl (HNO) has gained enormous attention because of its novel physiological or pharmacological properties, ranging from cardiovascular protective actions to antitumoricidal effects. Recent Advances: HNO is emerging as a new entity with therapeutic advantages over its redox sibling, NO. The interests in the chemical, pharmacological, and biological characteristics of HNO have broadened our current understanding of its role in physiology and pathophysiology. Critical Issues: In particular, the experimental evidence suggests the therapeutic potential of HNO in tumor pharmacology, such as neuroblastoma, gastrointestinal tumor, ovarian, lung, and breast cancers. Indeed, HNO donors have been demonstrated to attenuate tumor proliferation and angiogenesis. Future Directions: In this review, the generation and detection of HNO are outlined, and the roles of HNO in cancer progression are further discussed. We anticipate that the completion of this review might give novel insights into the roles of HNO in cancer pharmacology and open up a novel field of cancer therapy based on HNO.

14.
Molecules ; 24(15)2019 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-31390847

RESUMO

Diabetic kidney disease develops in approximately 40% of diabetic patients and is a major cause of chronic kidney diseases (CKD) and end stage kidney disease (ESKD) worldwide. Hydrogen sulfide (H2S), the third gasotransmitter after nitric oxide (NO) and carbon monoxide (CO), is synthesized in nearly all organs, including the kidney. Though studies on H2S regulation of renal physiology and pathophysiology are still in its infancy, emerging evidence shows that H2S production by renal cells is reduced under disease states and H2S donors ameliorate kidney injury. Specifically, aberrant H2S level is implicated in various renal pathological conditions including diabetic nephropathy. This review presents the roles of H2S in diabetic renal disease and the underlying mechanisms for the protective effects of H2S against diabetic renal damage. H2S may serve as fundamental strategies to treat diabetic kidney disease. These H2S treatment modalities include precursors for H2S synthesis, H2S donors, and natural plant-derived compounds. Despite accumulating evidence from experimental studies suggests the potential role of the H2S signaling pathway in the treatment of diabetic nephropathy, these results need further clinical translation. Expanding understanding of H2S in the kidney may be vital to translate H2S to be a novel therapy for diabetic renal disease.


Assuntos
Sulfeto de Hidrogênio/metabolismo , Animais , Nefropatias Diabéticas/tratamento farmacológico , Nefropatias Diabéticas/etiologia , Nefropatias Diabéticas/metabolismo , Nefropatias Diabéticas/patologia , Avaliação Pré-Clínica de Medicamentos , Fibrose , Humanos , Sulfeto de Hidrogênio/química , Sulfeto de Hidrogênio/farmacologia , Sulfeto de Hidrogênio/uso terapêutico , Glomérulos Renais/efeitos dos fármacos , Glomérulos Renais/metabolismo , Glomérulos Renais/patologia , Redes e Vias Metabólicas/efeitos dos fármacos , Óxido Nítrico/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Oxigênio/metabolismo , Podócitos/metabolismo , Podócitos/patologia , Sistema Renina-Angiotensina
15.
Int J Mol Sci ; 20(17)2019 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-31461977

RESUMO

Vascular calcification can be enhanced by hyperglycemia. Elastin loss in tunica media promotes the osteogenic transformation of smooth muscle cells (SMCs) and involves arterial medial calcification (AMC) that is associated with a high incidence of cardiovascular risk in patients with type 2 diabetes. Here, we tested whether hydrogen sulfide (H2S), an endogenous gaseous mediator, can prevent elastin loss and attenuate calcification induced by high glucose in SMCs. Calcification was induced by high glucose (4500 mg/L) in human aortic SMCs (HASMCs) under the condition of calcifying medium containing 10 mM ß-glycerophosphate (ß-GP). The experiments showed that NaHS (an H2S donor, 100 µM) mitigated the calcification of HASMCs treated with high glucose by decreasing calcium and phosphorus levels, calcium deposition and ALP activity and inhibited osteogenic transformation by increasing SMα-actin and SM22α, two phenotypic markers of smooth muscle cells, and decreasing core binding factor α-1 (Cbfα-1), a key factor in bone formation, protein expressions in HASMCs. Moreover, NaHS administration inhibited the activation of Stat3, cathepsin S (CAS) activity and its expression, but increased the level of elastin protein. Pharmacological inhibition or gene silencing Stat3 not only reversed elastin loss, but also attenuated CAS expression. Inhibition of CAS alleviated, while CAS overexpression exacerbated, elastin loss. Interestingly, overexpression of wild type (WT)-Stat3, but not its mutant C259S, elevated CAS protein expression and reduced elastin level. Moreover, NaHS induced S-sulfhydration in WT, but not in the C259S Stat3. These data suggest that H2S may directly regulate Cys259 residue in Stat3 and then impair its signaling function. Our data indicate that H2S may attenuate vascular calcification by upregulating elastin level through the inhibition of Stat3/CAS signaling.


Assuntos
Catepsinas/metabolismo , Elastina/metabolismo , Sulfeto de Hidrogênio/metabolismo , Miócitos de Músculo Liso/metabolismo , Fator de Transcrição STAT3/metabolismo , Calcificação Vascular/metabolismo , Cálcio/metabolismo , Células Cultivadas , Glucose/metabolismo , Humanos , Músculo Liso Vascular/citologia , Miócitos de Músculo Liso/efeitos dos fármacos , Fósforo/metabolismo , Transdução de Sinais , Sulfetos/farmacologia
16.
World J Gastroenterol ; 25(24): 3030-3043, 2019 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-31293339

RESUMO

BACKGROUND: Hepatocellular carcinoma (HCC) ranks second in terms of cancer mortality worldwide. Molecular magnetic resonance imaging (MRI) targeting HCC biomarkers such as alpha-fetoprotein (AFP) or glypican-3 (GPC3) offers new strategies to enhance specificity and help early diagnosis of HCC. However, the existing iron oxide nanoparticle-based MR molecular probes singly target AFP or GPC3, which may hinder their efficiency to detect heterogeneous micro malignant HCC tumors < 1 cm (MHCC). We hypothesized that the strategy of double antibody-conjugated iron oxide nanoparticles which simultaneously target AFP and GPC3 antigens may potentially be used to overcome the tumor heterogeneity and enhance the detection rate for MRI-based MHCC diagnosis. AIM: To synthesize an AFP/GPC3 double antibody-labeled iron oxide MRI molecular probe and to assess its impact on MRI specificity and sensitivity at the cellular level. METHODS: A double antigen-targeted MRI probe for MHCC anti-AFP-USPIO-anti-GPC3 (UAG) was developed by simultaneously conjugating AFP andGPC3 antibodies to a 5 nm ultra-small superparamagnetic iron oxide nanoparticle (USPIO). At the same time, the singly labeled probes of anti-AFP-USPIO (UA) and anti-GPC3-USPIO (UG) and non-targeted USPIO (U) were also prepared for comparison. The physical characterization including morphology (transmission electron microscopy), hydrodynamic size, and zeta potential (dynamic light scattering) was conducted for each of the probes. The antigen targeting and MRI ability for these four kinds of USPIO probes were studied in the GPC3-expressing murine hepatoma cell line Hepa1-6/GPC3. First, AFP and GPC3 antigen expression in Hepa1-6/GPC3 cells was confirmed by flow cytometry and immunocytochemistry. Then, the cellular uptake of USPIO probes was investigated by Prussian blue staining assay and in vitro MRI (T2-weighted and T2-map) with a 3.0 Tesla clinical MR scanner. RESULTS: Our data showed that the double antibody-conjugated probe UAG had the best specificity in targeting Hepa1-6/GPC3 cells expressing AFP and GPC3 antigens compared with single antibody-conjugated and unconjugated USPIO probes. The iron Prussian blue staining and quantitative T2-map MRI analysis showed that, compared with UA, UG, and U, the uptake of double antigen-targeted UAG probe demonstrated a 23.3% (vs UA), 15.4% (vs UG), and 57.3% (vs U) increased Prussian stained cell percentage and a 14.93% (vs UA), 9.38% (vs UG), and 15.3% (vs U) reduction of T2 relaxation time, respectively. Such bi-specific probe might have the potential to overcome tumor heterogeneity. Meanwhile, the coupling of two antibodies did not influence the magnetic performance of USPIO, and the relatively small hydrodynamic size (59.60 ± 1.87 nm) of double antibody-conjugated USPIO probe makes it a viable candidate for use in MHCC MRI in vivo, as they are slowly phagocytosed by macrophages. CONCLUSION: The bi-specific probe presents enhanced targeting efficiency and MRI sensitivity to HCC cells than singly- or non-targeted USPIO, paving the way for in vivo translation to further evaluate its clinical potential.


Assuntos
Carcinoma Hepatocelular/diagnóstico por imagem , Detecção Precoce de Câncer/métodos , Neoplasias Hepáticas/diagnóstico por imagem , Imagem por Ressonância Magnética/métodos , Sondas Moleculares/administração & dosagem , Animais , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Dextranos/administração & dosagem , Dextranos/química , Glipicanas/metabolismo , Imunoconjugados/administração & dosagem , Imunoconjugados/química , Neoplasias Hepáticas/patologia , Nanopartículas de Magnetita/administração & dosagem , Nanopartículas de Magnetita/química , Camundongos , Sondas Moleculares/química
17.
Head Neck ; 41(9): 3219-3225, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31116488

RESUMO

BACKGROUND: This study aimed to determine the effectiveness and safety of surgery combined with postoperative 125 I seed brachytherapy for treatment of primary mucoepidermoid carcinoma (MEC) of the parotid gland. METHODS: Retrospective analysis of data of patients with MEC (n = 108) treated with surgery plus postoperative 125 I seed brachytherapy between 2004 and 2016. Overall survival (OS), disease-free survival (DFS), local control rate (LCR), distant metastasis, and radiation-associated toxicities were analyzed, and factors affecting outcomes were evaluated. RESULTS: The 5- and 10-year OS were 98.8% and 95.8%, respectively. The DFS and LCR at 5 and 10 years were all 91.4%. Age ≥ 60 years (hazard ratio [HR] = 6.86, 95% confidence interval [CI]: 1.54-30.55) and T4 disease (HR = 7.15, 95% CI: 1.40-36.52) were poor prognostic factors. Acute radiation-associated toxicities were minor. CONCLUSION: Surgery plus 125 I seed brachytherapy appears to be an effective treatment for parotid gland MEC, capable of providing satisfactory outcomes with few complications.

18.
Cancers (Basel) ; 11(5)2019 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-31137518

RESUMO

Nanoparticle-based drug delivery systems are among the most popular research topics in recent years. Compared with traditional drug carriers, mesoporous silica nanoparticles (MSN) offer modifiable surfaces, adjustable pore sizes and good biocompatibility. Nanoparticle-based drug delivery systems have become a research direction for many scientists. With the active target factionalized, scientists could deliver drug carriers into cancer cells successfully. However, drugs in cancer cells could elicit drug resistance and induce cell exocytosis. Thus, the drug cannot be delivered to its pharmacological location, such as the nucleus. Therefore, binding the cell membrane and the nuclear target on the nanomaterial so that the anticancer drug can be delivered to its pharmacological action site is our goal. In this study, MSN-EuGd was synthesized by doping Eu3+ and Gd3+ during the synthesis of MSN. The surface of the material was then connected to the TAT peptide as the nucleus target for targeting the cancer nucleus and then loaded with the anticancer drug camptothecin (CPT). Then, the surface of MSN-EuGd was bonded to the hyaluronic acid as an active target and gatekeeper. With this system, it is possible and desirable to achieve dual imaging and dual targeting, as well as to deliver drugs to the cell nucleus under a hyaluronidase-controlled release. The experimental approach is divided into three parts. First, we conferred the material with fluorescent and magnetic dual-imaging property by doping Eu3+ and Gd3+ into the MSN. Second, modification of the cell membrane target molecule and the nucleus target molecule occurred on the surface of the nanoparticle, making the nanoparticle a target drug carrier. Third, the loading of drug molecules into the carrier gave the entire carrier a specific target profile and enabled the ability to treat cancer. In this study, we investigated the basic properties of the drug carrier, including physical properties, chemical properties, and in vitro tests. The result showed that we have successfully designed a drug delivery system that recognizes normal cells and cancer cells and has good anticancer effects.

19.
Asian J Surg ; 42(10): 899-906, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30914154

RESUMO

To provide a meta-analysis of studies evaluating long-term all-cause mortality, aneurysm-related mortality and re-intervention after open or endovascular repair for abdominal aortic aneurysm. Electronic bibliographic sources were interrogated using a combination of free text and controlled vocabulary searches to identify studies comparing the long-term outcomes of open and endovascular repair for abdominal aortic aneurysm. The review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement standards. Fixed effect or random effects models were used. We retrieved 4 randomized controlled trials (RCTs; 2,783 patients), 7 nonrandomized trials (86,035 patients). The primary outcome was all-cause mortality. Heterogeneity was high and publication bias could not be excluded. Despite these limitations, the analysis showed that open and endovascular abdominal aortic aneurysm repair had similar all-cause mortality (OR 1.16, 95% CI, 0.89-1.51) over 5 years follow up, which was maintained after at least 10 years of follow-up (OR 0.87, 95% CI, 0.73-1.03). There was no significant difference in aneurysm-related mortality by 5 years or longer follow-up. A significantly lower proportion of patients undergoing open repair required reintervention (OR 0.38, 95% CI 0.24-0.64), which was maintained over 5 years of follow-up. There is no long-term survival difference between the patients who underwent open or endovascular aneurysm repair. There is significantly higher risk of reinterventions after endovascular aneurysm repair.


Assuntos
Aorta Abdominal/cirurgia , Aneurisma da Aorta Abdominal/cirurgia , Procedimentos Endovasculares/métodos , Procedimentos Cirúrgicos Vasculares/métodos , Aneurisma da Aorta Abdominal/mortalidade , Bases de Dados Bibliográficas , Procedimentos Endovasculares/mortalidade , Seguimentos , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Reoperação/estatística & dados numéricos , Risco , Taxa de Sobrevida , Fatores de Tempo , Resultado do Tratamento , Procedimentos Cirúrgicos Vasculares/mortalidade
20.
Brachytherapy ; 18(2): 217-223, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30638911

RESUMO

PURPOSE: We sought to investigate the feasibility and accuracy of computer-assisted techniques in the interstitial brachytherapy of the deep regions of the head and neck. MATERIALS AND METHODS: A computer-assisted brachytherapy workflow was applied to 10 patients with tumors in the deep regions of the head and neck. Based on the brachytherapy treatment preplan, we constructed a digital stereotactic model to accurately transfer the virtual plan into the navigation system, and subsequently printed the individual templates. The navigation system and the individual template were combined together to visualize and guide brachytherapy needle implantation. Preoperative and intraoperative image data were reconstructed and registered to measure and analyze the needle deviation. RESULTS: A total of 58 needles were successfully inserted in 10 patients with the guidance of computer-assisted techniques and a mean deviation of 5.2 mm. The inserting trajectories and depths of the needles were as follows: from the parotid and masseter regions to the infratemporal fossa or skull base, the range was 15.7-74.6 mm; from the submandibular and retromandibular regions to the infratemporal fossa or skull base, the range was 15.6-70.6 mm; from the infraorbital region to the pterygomandibular region, the range was 63.7-69.7 mm; and from the periorbital region to the intraorbital region, the range was 47.6-61.8 mm. The dose distribution met the treatment requirement well. CONCLUSIONS: The computer-assisted interstitial brachytherapy workflow was proven to be feasible and accurate for the deep regions of the head and neck.


Assuntos
Braquiterapia/métodos , Neoplasias de Cabeça e Pescoço/radioterapia , Planejamento da Radioterapia Assistida por Computador/métodos , Estudos de Viabilidade , Neoplasias de Cabeça e Pescoço/diagnóstico por imagem , Humanos , Agulhas , Tomografia Computadorizada por Raios X
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