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1.
Mol Biol Evol ; 41(3)2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38318973

RESUMO

Mountains are the world's most important centers of biodiversity. The Sino-Himalayan Mountains are global biodiversity hotspot due to their extremely high species richness and endemicity. Ample research investigated the impact of the Qinghai-Tibet Plateau uplift and Quaternary glaciations in driving species diversification in plants and animals across the Sino-Himalayan Mountains. However, little is known about the role of landscape heterogeneity and other environmental features in driving diversification in this region. We utilized whole genomes and phenotypic data in combination with landscape genetic approaches to investigate population structure, demography, and genetic diversity in a forest songbird species native to the Sino-Himalayan Mountains, the red-billed leiothrix (Leiothrix lutea). We identified 5 phylogeographic clades, including 1 in the East of China, 1 in Yunnan, and 3 in Tibet, roughly consistent with differences in song and plumage coloration but incongruent with traditional subspecies boundaries. Isolation-by-resistance model best explained population differentiation within L. lutea, with extensive secondary contact after allopatric isolation leading to admixture among clades. Ecological niche modeling indicated relative stability in the extent of suitable distribution areas of the species across Quaternary glacial cycles. Our results underscore the importance of mountains in the diversification of this species, given that most of the distinct genetic clades are concentrated in a relatively small area in the Sino-Himalayan Mountain region, while a single shallow clade populates vast lower-lying areas to the east. This study highlights the crucial role of landscape heterogeneity in promoting differentiation and provides a deep genomic perspective on the mechanisms through which diversity hotspots form.


Assuntos
Deriva Genética , Passeriformes , Animais , China , Filogeografia , Florestas , Passeriformes/genética , Filogenia , Variação Genética
2.
Syst Biol ; 2023 Dec 29.
Artigo em Inglês | MEDLINE | ID: mdl-38157277

RESUMO

Different genomic regions may reflect conflicting phylogenetic topologies primarily due to incomplete lineage sorting and/or gene flow. Genomic data are necessary to reconstruct the true species tree and explore potential causes of phylogenetic conflict. Here, we investigate the phylogenetic relationships of four Emberiza species (Aves: Emberizidae) and discuss the potential causes of the observed mitochondrial non-monophyly of Emberiza godlewskii (Godlewski's bunting) using phylogenomic analyses based on whole genome resequencing data from 41 birds. Analyses based on both the whole mitochondrial genome and ~39 kilobases from the non-recombining W chromosome reveal sister relationships between each the northern and southern populations of E. godlewskii with E. cioides and E. cia, respectively. In contrast, the monophyly of E. godlewskii is reflected by the phylogenetic signal of autosomal and Z chromosomal sequence data as well as demographic inference analyses, which - in combination - support the following tree topology: (((E. godlewskii, E. cia), E. cioides), E. jankowskii). Using D-statistics, we detected multiple gene flow events among different lineages, indicating pervasive introgressive hybridization within this clade. Introgression from an unsampled lineage that is sister to E. cioides or introgression from an unsampled mitochondrial + W chromosomal lineage of E. cioides into northern E. godlewskii may explain the phylogenetic conflict between the species tree estimated from genome-wide data versus mtDNA/W tree topologies. These results underscore the importance of using genomic data for phylogenetic reconstruction and species delimitation.

3.
Inorg Chem ; 63(3): 1507-1512, 2024 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-38198122

RESUMO

Single-step ethylene (C2H4) production from acetylene (C2H2), ethylene (C2H4), and ethane (C2H6) mixtures was realized via the strategy of a flow channel with recognition corners in MOF NTUniv-64. Both the uptake amounts and the enthalpy of adsorption (Qst) showed the same order of C2H2 > C2H6 > C2H4. Breakthrough testing also verified the above data and the C2H4 purification ability. Grand Canonical Monte Carlo (GCMC) simulations indicated that uneven corners could precisely detain C2H2 and C2H6, in which the C-H···π interaction distance between C2H2 (2.84 Å) and C2H6 (3.03 Å) and the framework was shorter than that of C2H4 (3.85 Å).

4.
Inorg Chem ; 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38949263

RESUMO

The single-step purification of ethylene (C2H4) from a mixture of carbon dioxide (CO2), acetylene (C2H2), ethylene (C2H4), and ethane (C2H6) was achieved through MOF Compound-1, where the aromatic pore surface and carboxylates selectively recognized C2H6 and CO2, respectively, resulting in a reversal of the adsorption orders for both gases (C2H6 > C2H4 and CO2 > C2H4). Breakthrough testing verified that the C2H4 purification ability could be enhanced 2.6 times after adding impure CO2. Grand Canonical Monte Carlo (GCMC) simulations demonstrate that there are interactions between CO2 and C2H6 molecules as well as between CO2 molecules themselves. These interactions contribute to the enhancement of the C2H4 purification ability upon the addition of CO2 and the increased adsorption of CO2.

5.
Inorg Chem ; 63(16): 7113-7117, 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38578870

RESUMO

The strategy of flow channel with wrinkles and calcium sites for single-step C2H4 purification from C2 gases and methanol-to-olefins (MTO) products separation was realized in FJI-Y9. The adsorption amounts showed a total reversal order of C3H6 > C2H6 > C2H2 > C2H4 at 298 K. Modeling indicated that the wrinkles and Ca2+ facilitated the full contact of C3H6 and C2H6. Breakthrough experiments illustrated that FJI-Y9 could yield pure C2H4 in a single step with a productivity of 0.78 mmol g-1. In a lone adsorption/desorption cycle for MTO product separation, the productivities of C3H6 and C2H4 were 1.96 and 1.29 mol g-1, standing as the highest recorded values.

6.
Surg Endosc ; 37(1): 148-155, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-35879570

RESUMO

BACKGROUND: Omental wrapping (OW) is the leading cause of obstruction of the peritoneal dialysis (PD) catheter, which interferes with dialysis treatment. Routinely or selectively performing omentopexy during laparoscopic PD catheter placement has been suggested to prevent OW. However, most of the published techniques for performing this adjunctive procedure require additional incisions and suturing. Herein, we aimed to report our experience in performing omentopexy with a sutureless technique during dual-incision PD catheter insertion. We also performed a comparative analysis to assess the benefit/risk profile of routine omentopexy in these patients. METHODS: This retrospective study enrolled 469 patients who underwent laparoscopic PD catheter insertion. Their demographic characteristics and operative details were collected from the database of our institution. Omentopexy was performed by fixing the inferior edge of the omentum to the round ligament of the liver using titanium clips. For analysis, the patients were divided into the omentopexy group and the non-omentopexy group. We also reviewed the salvage management and outcomes of patients who experienced OW. RESULTS: The patients were categorized into the omentopexy (n = 81) and non-omentopexy (n = 388) groups. The patients in the non-omentopexy group had a higher incidence of OW, whereas no patient in the omentopexy group experienced this complication (5.2% vs. 0.0%, p = 0.033). The median operative time was 27 min longer in patients who underwent omentopexy than in those who did not [100 (82-118) min vs. 73 (63-84) min, p < 0.001]. One patient had an intra-abdominal hematoma after omentopexy and required salvage surgery to restore catheter function. The complication rate of omentopexy was 1.2% (1/81). CONCLUSION: Sutureless omentopexy during laparoscopic PD catheter insertion is a safe and reliable technique that does not require additional incisions and suturing. Routinely performing omentopexy provides clinical benefits by reducing the risk of catheter dysfunction due to OW.


Assuntos
Falência Renal Crônica , Laparoscopia , Diálise Peritoneal , Feminino , Humanos , Omento/cirurgia , Estudos Retrospectivos , Diálise Peritoneal/métodos , Catéteres , Laparoscopia/métodos , Falência Renal Crônica/cirurgia , Cateteres de Demora
7.
Medicina (Kaunas) ; 59(6)2023 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-37374218

RESUMO

Background and Objectives: In peritoneal dialysis (PD) therapy, intra-abdominal adhesions (IAAs) can cause catheter insertion failure, poor dialysis function, and decreased PD adequacy. Unfortunately, IAAs are not readily visible to currently available imaging methods. The laparoscopic approach for inserting PD catheters enables direct visualization of IAAs and simultaneously performs adhesiolysis. However, a limited number of studies have investigated the benefit/risk profile of laparoscopic adhesiolysis in patients receiving PD catheter placement. This retrospective study aimed to address this issue. Materials and Methods: This study enrolled 440 patients who received laparoscopic PD catheter insertion at our hospital between January 2013 and May 2020. Adhesiolysis was performed in all cases with IAA identified via laparoscopy. We retrospectively reviewed data, including clinical characteristics, operative details, and PD-related clinical outcomes. Results: These patients were classified into the adhesiolysis group (n = 47) and the non-IAA group (n = 393). The clinical characteristics and operative details had no remarkable between-group differences, except the percentage of prior abdominal operation history was higher and the median operative time was longer in the adhesiolysis group. PD-related clinical outcomes, including incidence rate of mechanical obstruction, PD adequacy (Kt/V urea and weekly creatinine clearance), and overall catheter survival, were all comparable between the adhesiolysis and non-IAA groups. None of the patients in the adhesiolysis group suffered adhesiolysis-related complications. Conclusions: Laparoscopic adhesiolysis in patients with IAA confers clinical benefits in achieving PD-related outcomes comparable to those without IAA. It is a safe and reasonable approach. Our findings provide new evidence to support the benefits of this laparoscopic approach, especially in patients with a risk of IAAs.


Assuntos
Laparoscopia , Diálise Peritoneal , Humanos , Estudos Retrospectivos , Cateteres de Demora , Diálise Renal , Diálise Peritoneal/efeitos adversos , Laparoscopia/efeitos adversos , Laparoscopia/métodos , Peritônio
8.
J Clin Immunol ; 42(8): 1730-1741, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35947322

RESUMO

PURPOSE: Anti-granulocyte-macrophage colony-stimulating factor autoantibodies (anti-GM-CSF Abs) are a predisposing factor for pulmonary alveolar proteinosis (PAP) and Cryptococcus gattii cryptococcosis. This study aimed to investigate clinical manifestations in anti-GM-CSF Ab-positive patients with C. gattii cryptococcosis and analyze the properties of anti-GM-CSF Abs derived from these patients and patients with PAP. METHODS: Thirty-nine patients diagnosed with cryptococcosis (caused by C. neoformans or C. gattii) and 6 with PAP were enrolled in the present study. Clinical information was obtained from medical records. Blood samples were collected for analysis of autoantibody properties. We also explored the National Health Insurance Research Database (NHIRD) of Taiwan to investigate the epidemiology of cryptococcosis and PAP. RESULTS: High titers of neutralizing anti-GM-CSF Abs were identified in 15 patients with cryptococcosis (15/39, 38.5%). Most anti-GM-CSF Ab-positive cryptococcosis cases had central nervous system (CNS) involvement (14/15, 93.3%). Eleven out of 14 (78.6%) anti-GM-CSF Ab-positive CNS cryptococcosis patients were confirmed to be infected with C. gattii, and PAP did not occur synchronously or metachronously in a single patient from our cohort. Exploration of an association between HLA and anti-GM-CSF Ab positivity or differential properties of autoantibodies from cryptococcosis patients and PAP yielded no significant results. CONCLUSION: Anti-GM-CSF Abs can cause two diseases, C. gattii cryptococcosis and PAP, which seldom occur in the same subject. Current biological evidence regarding the properties of anti-GM-CSF Abs cannot provide clues regarding decisive mechanisms. Further analysis, including more extensive cohort studies and investigations into detailed properties, is mandatory to better understand the pathogenesis of anti-GM-CSF Abs.


Assuntos
Criptococose , Proteinose Alveolar Pulmonar , Humanos , Autoanticorpos , Criptococose/diagnóstico , Criptococose/epidemiologia , Proteinose Alveolar Pulmonar/diagnóstico , Proteinose Alveolar Pulmonar/etiologia , Fator Estimulador de Colônias de Granulócitos e Macrófagos/imunologia
9.
FASEB J ; 35(3): e21414, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33583095

RESUMO

Low back pain (LBP) is a major clinical problem that lacks effective treatments. The sensory innervation in porous vertebral endplates and anxiety contributes to spinal hyperalgesia. We hypothesized that SIRT1 activator resveratrol alleviates LBP and anxiety via promotion of osteogenesis in the porous endplates. The hyperalgesia and anxiety-related behaviors; sensory innervation, inflammation and porosity of endplates; and osteogenic/osteoclastic factors expression were measured following resveratrol treatment after lumbar spine instability (LSI) surgery. To explore whether resveratrol promotes endplates osteogenesis and thus alleviates LBP through activation of SIRT1 in the osteoprogenitor cells of endplates, SIRT1OSX-/- mice were employed. Additionally, the levels of inflammation markers, phosphorylation of cAMP response element-binding protein (pCREB), and brain-derived neurotrophic factor (BDNF) in hippocampus were evaluated. After 4 or 8 weeks LSI surgery, the mice suffered from hyperalgesia and anxiety, which were efficiently attenuated by resveratrol at 8 weeks. Resveratrol treatment-enhanced osteogenesis and decreased endplates porosities accompanied with the reduction of TNFα, IL-1ß, and COX2 levels and CGRP+ nerve fibers innervation in porous endplates. Resveratrol-mediated endplates osteogenesis, decreased endplates porosities, and analgesic and antianxiety effects were abrogated in SIRT1OSX-/- mice. Furthermore, resveratrol relieved inflammation and increased pCREB and BDNF expression in the hippocampus after 8 weeks, which alleviate anxiety-related behaviors. This study provides that resveratrol-mediated porous endplates osteogenesis via the activation of SIRT1 markedly blocked sensory innervation and inflammation in endplates, therefore, alleviating LSI surgery-induced LBP and hippocampus-related anxiety.


Assuntos
Ansiedade/tratamento farmacológico , Comportamento Animal/efeitos dos fármacos , Dor Lombar/tratamento farmacológico , Osteogênese/efeitos dos fármacos , Resveratrol/farmacologia , Sirtuína 1/efeitos dos fármacos , Animais , Ansiolíticos/farmacologia , Ansiedade/metabolismo , Comportamento Animal/fisiologia , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Dor Lombar/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Osteoclastos/efeitos dos fármacos , Osteoclastos/metabolismo
10.
Curr Treat Options Oncol ; 23(9): 1303-1319, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35976553

RESUMO

OPINION STATEMENT: Gastrointestinal stromal tumor (GIST), though rare, is the most common mesenchymal tumors of the gastrointestinal tract. KIT or PDGFRα mutation plays as an oncogenic driver in the majority of GISTs. Surgical resection is the only curative treatment for localized disease. The discovery of imatinib with promising anti-tumor effect and successive tyrosine kinase inhibitors (TKI), including second-line sunitinib and third-line regorafenib, revolutionized the management of advanced and metastatic GIST over the past two decades. Recently, ripretinib and avapritinib were approved for the fourth line setting and for PDGFRA exon 18-mutant GIST in first-line setting, respectively. Despite multi-line TKIs exerted ability of disease control, drug resistance remained an obstacle for preventing rapid disease progression. Experimental TKIs or novel therapeutic targets may further improve treatment efficacy. Immune checkpoint inhibitors such as anti-programmed cell death protein-1 (PD1) and anti-CTL-associated antigen 4 (CTLA-4) showed moderate response in early phase trials composed of heavily pretreated patients. KIT/PDGFRα wild-type GISTs are generally less sensitive to imatinib and late-line TKIs. Recent studies demonstrated that targeting fibroblast growth factor receptor signaling may be a potential target for the wild-type GISTs.


Assuntos
Antineoplásicos , Neoplasias Gastrointestinais , Tumores do Estroma Gastrointestinal , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Resistencia a Medicamentos Antineoplásicos/genética , Neoplasias Gastrointestinais/tratamento farmacológico , Neoplasias Gastrointestinais/genética , Neoplasias Gastrointestinais/patologia , Tumores do Estroma Gastrointestinal/tratamento farmacológico , Tumores do Estroma Gastrointestinal/genética , Tumores do Estroma Gastrointestinal/patologia , Humanos , Mesilato de Imatinib/uso terapêutico , Mutação , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Receptor alfa de Fator de Crescimento Derivado de Plaquetas/genética , Sunitinibe/uso terapêutico
11.
J Vasc Res ; : 1-16, 2021 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-33535226

RESUMO

MicroRNAs and sirtuins are important epigenetic regulators of gene expression and both contribute significantly to postnatal vascular development. However, the crosstalk between miRNAs and sirtuins in the modulation of angiogenesis has rarely been discussed. Here, we investigated the interactions between miR-138 and sirtuins in the process of angiogenesis. We found that overexpression of miR-138 markedly suppressed the proliferation, migration, and tube-forming capacities of the endothelial cells. And, miR-138 inhibitor-treated endothelial cells showed a reversed phenotype. Furthermore, miR-138 plays a negative role in vascular development in vivo. Western blot and qPCR assays demonstrated that SIRT1 was silenced by miR-138, and a luciferase reporter assay showed that miR-138 bound to the 3'-UTR of SIRT1. The re-expression of SIRT1 alleviated miR-138-mediated suppression of angiogenesis. Furthermore, silencing SIRT1 could boost the level of miR-138. And, upon miR-138 inhibitor treatment, SIRT1 silencing no longer reduced the angiogenic ability of endothelial cells significantly. These results demonstrated that the circuitry involving miR-138 and SIRT1 may participate in vascular homeostasis and also offered the possibility of identifying a new approach in the treatment of angiogenic diseases.

12.
Surg Endosc ; 35(12): 6623-6632, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-33258028

RESUMO

BACKGROUND: Acute cholecystitis (AC) is a common surgical emergency. The Tokyo Guidelines 2018 (TG18) provides a reliable algorithm for the treatment of AC patients to achieve optimal outcomes. However, the economic benefits have not been validated. We hypothesize that good outcomes and cost savings can both be achieved if patients are treated according to the TG18. METHOD: This retrospective study included 275 patients who underwent cholecystectomy in a 15-month span. Patients were divided into three groups (group 1: mild AC; group 2: moderate AC with American Society of Anesthesiologists (ASA) physical status class ≤ 2 and Charlson Comorbidity Index (CCI) score ≤ 5; and group 3: moderate AC with ASA class ≥ 3, CCI score ≥ 6, or severe AC). Each group was further divided into two subgroups according to management (followed or deviated from the TG18). Patient demographics, clinical outcomes, and hospital costs were compared. RESULTS: For group 1 patients, 77 (81%) were treated according to the TG18 and had a significantly higher successful laparoscopic cholecystectomy (LC) rate (100%), lower hospital cost ($1896 vs $2388), and shorter hospital stay (2.9 vs 8 days) than those whose treatment deviated from the TG18. For group 2 patients, 50 (67%) were treated according to the TG18 and had a significantly lower hospital cost ($1926 vs $2856), shorter hospital stay (3.9 vs 9.9 days), and lower complication rate (0% vs 12.5%). For group 3 patients, 62 (58%) were treated according to the TG18 and had a significantly lower intensive care unit (ICU) admission rate (9.7% vs 25%), but a longer hospital stay (12.6 vs 7.8 days). However, their hospital costs were similar. Early LC in group 3 patients did not have economic benefits over gallbladder drainage and delayed LC. CONCLUSION: The TG18 are the state-of-the-art guidelines for the treatment of AC, achieving both satisfactory outcomes and cost-effectiveness.


Assuntos
Colecistectomia Laparoscópica , Colecistite Aguda , Colecistite Aguda/cirurgia , Gastos em Saúde , Humanos , Tempo de Internação , Estudos Retrospectivos , Tóquio , Resultado do Tratamento
13.
J Nanobiotechnology ; 19(1): 390, 2021 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-34823543

RESUMO

BACKGROUND: Although lower temperature (< 45 °C) photothermal therapy (LPTT) have attracted enormous attention in cancer therapy, the therapeutic effect is still unsatisfying when applying LPTT alone. Therefore, combining with other therapies is urgently needed to improve the therapeutic effect of LPTT. Recently reported oxygen-irrelevant free radicals based thermodynamic therapy (TDT) exhibit promising potential for hypoxic tumor treatment. However, overexpression of glutathione (GSH) in cancer cells would potently scavenge the free radicals before their arrival to the specific site and dramatically diminish the therapeutic efficacy. METHODS AND RESULTS: In this work, a core-shell nanoplatform with an appropriate size composed of arginine-glycine-aspartate (RGD) functioned polydopamine (PDA) as a shell and a triphenylphosphonium (TPP) modified hollow mesoporous manganese dioxide (H-mMnO2) as a core was designed and fabricated for the first time. This nanostructure endows a size-controllable hollow cavity mMnO2 and thickness-tunable PDA layers, which effectively prevented the pre-matured release of encapsulated azo initiator 2,2'-azobis[2-(2-imidazolin-2-yl) propane] dihydrochloride (AIBI) and revealed pH/NIR dual-responsive release performance. With the mitochondria-targeting ability of TPP, the smart nanocomposites (AIBI@H-mMnO2-TPP@PDA-RGD, AHTPR) could efficiently induce mitochondrial associated apoptosis in cancer cells at relatively low temperatures (< 45 °C) via selectively releasing oxygen-irrelevant free radicals in mitochondria and facilitating the depletion of intracellular GSH, exhibiting the advantages of mitochondria-targeted LPTT/TDT. More importantly, remarkable inhibition of tumor growth was observed in a subcutaneous xenograft model of osteosarcoma (OS) with negligible side effects. CONCLUSIONS: The synergistic therapy efficacy was confirmed by effectively inducing cancer cell death in vitro and completely eradicating the tumors in vivo. Additionally, the excellent biosafety and biocompatibility of the nanoplatforms were confirmed both in vitro and in vivo. Taken together, the current study provides a novel paradigm toward oxygen-independent free-radical-based cancer therapy, especially for the treatment of hypoxic solid tumors.


Assuntos
Radicais Livres , Nanopartículas Metálicas/química , Mitocôndrias , Sistemas de Liberação de Fármacos por Nanopartículas , Terapia Fototérmica , Animais , Compostos Azo/química , Linhagem Celular Tumoral , Temperatura Baixa , Feminino , Radicais Livres/análise , Radicais Livres/metabolismo , Humanos , Imidazóis/química , Compostos de Manganês/química , Camundongos , Camundongos Nus , Mitocôndrias/química , Mitocôndrias/metabolismo , Óxidos/química
14.
J Nanobiotechnology ; 19(1): 221, 2021 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-34315494

RESUMO

BACKGROUND: Despite advances of surgery and neoadjuvant chemotherapy during the past few decades, the therapeutic efficacy of current therapeutic protocol for osteosarcoma (OS) is still seriously compromised by multi-drug resistance and severe side effects. Amplification of intracellular oxidative stress is considered as an effective strategy to induce cancer cell death. The purpose of this study was to develop a novel strategy that can amplify the intracellular oxidative stress for synergistic cascade cancer therapy. METHODS AND RESULTS: A novel nanocomposite, composed of folic acid (FA) modified mesoporous silica-coated gold nanostar (GNS@MSNs-FA) and traditional Chinese medicine lycorine (Ly), was rationally designed and developed. Under near-infrared (NIR) irradiation, the obtained GNS@MSNs-FA/Ly could promote a high level of ROS production via inducing mitochondrial dysfunction and potent endoplasmic reticulum (ER) stress. Moreover, glutathione (GSH) depletion during ER stress could reduce ROS scavenging and further enable efficient amplification of intracellular oxidative stress. Both in vitro and in vivo studies demonstrated that GNS@MSNs-FA/Ly coupled with NIR irradiation exhibited excellent antitumor efficacy without noticeable toxicity in MNNG/HOS tumor-bearing mice. CONCLUSION: All these results demonstrated that GNS@MSNs-FA/Ly coupled with NIR irradiation could dramatically amplify the intra-tumoral oxidative stress, exhibiting excellent antitumor ability without obvious systemic toxicity. Taken together, this promising strategy provides a new avenue for the effective cancer synergetic therapy and future clinical translation.


Assuntos
Alcaloides de Amaryllidaceae/farmacologia , Ouro/química , Nanocompostos/química , Neoplasias/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Fenantridinas/farmacologia , Animais , Materiais Biocompatíveis , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Estresse do Retículo Endoplasmático , Ácido Fólico , Humanos , Camundongos , Microscopia de Fluorescência , Mitocôndrias , Nanocompostos/uso terapêutico , Neoplasias/patologia , Osteossarcoma , Espécies Reativas de Oxigênio , Dióxido de Silício
15.
J Cell Mol Med ; 24(9): 5274-5289, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32207235

RESUMO

Chemoresistance is the main obstacle of treatment in patients with osteosarcoma. RNA-binding protein PTBP1 has been identified as an oncogene in various cancers. However, the role of PTBP1 in osteosarcoma, especially in chemoresistant osteosarcoma, and the underlying mechanism remain unclear. In this study, we aimed to explore the functions of PTBP1 in chemoresistance of osteosarcoma. We found that PTBP1 was significantly increased in chemotherapeutically insensitive osteosarcoma tissues and cisplatin-resistant osteosarcoma cell lines (MG-63CISR and U-2OSCISR ) as compared to chemotherapy-sensitive osteosarcoma tissues and cell lines. Knock-down of PTBP1 can enhance the anti-proliferation and apoptosis-induced effects of cisplatin in MG-63CISR and U-2OSCISR cells. Moreover, PTBP1 knock-down significantly up-regulated the expression of the copper transporter SLC31A1, as indicated by transcriptome sequencing. Through RNA immunoprecipitation, dual-luciferase reporter assay and RNA stability detection, we confirmed that PTBP1 binds to SLC31A1 mRNA and regulates the expression level of SLC31A1 by affecting mRNA stability. Additionally, SLC31A1 silencing abrogated the chemosensitizing effect of PTBP1 knock-down in MG-63CISR and U-2OSCISR cells. Using a nude mouse xenograft model, we further confirmed that PTBP1 knock-down enhanced chemoresistant osteosarcoma responsiveness to cisplatin treatment in vivo. Collectively, the present study suggests that PTBP1 is a crucial determinant of chemoresistance in osteosarcoma.


Assuntos
Cisplatino/uso terapêutico , Transportador de Cobre 1/genética , Resistencia a Medicamentos Antineoplásicos/genética , Regulação Neoplásica da Expressão Gênica , Ribonucleoproteínas Nucleares Heterogêneas/metabolismo , Osteossarcoma/tratamento farmacológico , Osteossarcoma/genética , Proteína de Ligação a Regiões Ricas em Polipirimidinas/metabolismo , Adolescente , Animais , Apoptose/efeitos dos fármacos , Apoptose/genética , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/genética , Neoplasias Ósseas/patologia , Linhagem Celular Tumoral , Criança , Cisplatino/farmacologia , Transportador de Cobre 1/metabolismo , Regulação para Baixo/genética , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Feminino , Inativação Gênica , Ribonucleoproteínas Nucleares Heterogêneas/genética , Humanos , Masculino , Camundongos Nus , Osteossarcoma/patologia , Proteína de Ligação a Regiões Ricas em Polipirimidinas/genética , Prognóstico , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Regulação para Cima/efeitos dos fármacos , Regulação para Cima/genética , Adulto Jovem
16.
World J Surg ; 44(9): 2985-2992, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32383055

RESUMO

BACKGROUND: The advanced technology of interventional radiology may contribute to a rapid and timely angioembolization for hemostasis. We hypothesized that unstable hemodynamics is no longer an absolute contraindication of nonoperative management (NOM) in blunt splenic injury patients using rapid angioembolization. METHODS: From January 2009 to December 2019, blunt splenic injury patients with unstable hemodynamics [initial pulse >120 beats/min or systolic blood pressure <90 mm Hg] were included. Either emergency surgery or angioembolization was performed for hemostasis because of their unstable status. The characteristics of patients who underwent angioembolization or surgery were compared in each group (all patients, patients with hypotension, patients without response to resuscitation and hypotensive patients without response to resuscitation). RESULTS: A total of 73 patients were included in the current study. With respect to all patients, 68.5% (N = 50) of patients underwent NOM with angioembolization for hemostasis. Patients who underwent angioembolization for hemostasis had a significantly lower base deficit (5.3 ± 3.8 vs. 8.3 ± 5.2 mmol/L, p = 0.006) and a higher proportion of response to resuscitation (82.0% vs. 30.4%, p < 0.001) than did patients who underwent surgery. However, there was no significant difference in the proportion of hypotension (58.0% vs. 65.2%, p = 0.558) between these two groups. There were 44 patients with hypotension, and the angioembolization could be performed in 65.9% (N = 29) of them. Patients who underwent angioembolization had a significantly higher proportion of response to resuscitation than did patients who underwent surgery (89.7% vs. 33.3%, p < 0.001). In hypotensive patients without response to resuscitation (N = 13), 23.1% (N = 3) of the patients underwent angioembolization successfully. There was no significant difference in time to hemostasis procedure between patients who underwent angioembolization or surgery (24.7 ± 2.1 vs. 26.3 ± 16.7 min, p = 0.769). The demographics, vital signs, blood transfusion amount, injury severity, mortality rate and length of stay of patients who underwent angioembolization were not significantly different from patients who underwent surgery in each group. CONCLUSIONS: With a short preparation time of angioembolization, the NOM could be performed selectively for hemodynamically unstable patients with blunt splenic injury. The base deficit serves as an early detector of the requirement of surgical treatment.


Assuntos
Embolização Terapêutica/métodos , Hemodinâmica/fisiologia , Baço/lesões , Ferimentos não Penetrantes/terapia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Técnicas Hemostáticas , Humanos , Hipotensão/terapia , Masculino , Pessoa de Meia-Idade , Ressuscitação , Estudos Retrospectivos , Ferimentos não Penetrantes/fisiopatologia , Adulto Jovem
17.
BMC Surg ; 20(1): 179, 2020 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-32762661

RESUMO

BACKGROUND: Submucosal tumors (SMTs) of different etiologies exist from esophagus to rectum. Esophagogastric junction (EGJ) is one of the known difficult locations for tumor resection. Although minimally invasive surgery (MIS) is a well-established approach for gastrointestinal surgery, there is no consensus that MIS for resection of SMTs around EGJ is superior to laparotomy. We tried to clarify the factors that determine the surgeons' choices between these two approaches. METHODS: From January 2002 to June 2016, 909 patients with SMTs underwent resection in our department. Among them, 119 patients (13%) had SMTs around EGJ were enrolled by retrospective review. The clinicopathological features and tumor-related parameters were reviewed and analyzed. RESULTS: The cohort was stratified into three groups according to the extent of gastrectomy and surgical approaches. The three groups are as following: major gastrectomy (n = 13), minor gastrectomy by laparotomy (n = 51), and minor gastrectomy with MIS (n = 55). The average tumor size was significantly larger in the major gastrectomy group than in the two minor gastrectomy groups; however, there was no difference between the two minor gastrectomy groups (5.33 cm, 4.07 cm, and 3.69 cm, respectively). The minor gastrectomy with MIS required least hospital stay and operation duration also. We re-stratify the two minor gastrectomy groups (n = 106) according to the orientation of SMTs around the EGJ into 4 zones. Most of SMTs located on the greater curvature side of the EGJ were resected with MIS (82% versus 18%), whereas SMTs in the other zones were resected more often by laparotomy (59% versus 41%). There was no surgical mortality within the cohort, while minor gastrectomy with MIS yielded least number of leakages among the three groups. CONCLUSIONS: For SMTs around the EGJ, larger tumors (diameter of more than 5 cm) are more likely to be resected with major gastrectomy. To resect SMTs around the EGJ in a wedge-like (minor gastrectomy) fashion, tumors located other than the greater curvature side were more often resected by laparotomy. However, MIS yielded acceptable safety and surgical outcomes compared to conventional laparotomy for SMTs around the EGJ of the same size.


Assuntos
Gastrectomia , Laparoscopia , Neoplasias Gástricas , Adulto , Idoso , Junção Esofagogástrica/patologia , Junção Esofagogástrica/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Neoplasias Gástricas/cirurgia
18.
J Formos Med Assoc ; 119(9): 1343-1352, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31395463

RESUMO

The incidence of acute pancreatitis and related health care utilization are increasing. Acute pancreatitis may result in organ failure and various local complications with risks of morbidity and even mortality. Recent advances in research have provided novel insights into the assessment and management for acute pancreatitis. This consensus is developed by Taiwan Pancreas Society to provide an updated, evidence-based framework for managing acute pancreatitis.


Assuntos
Pancreatite , Doença Aguda , Consenso , Humanos , Pancreatite/diagnóstico , Pancreatite/terapia , Taiwan/epidemiologia
19.
J Shoulder Elbow Surg ; 29(4): 845-852, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32197769

RESUMO

BACKGROUND: Cubitus varus deformity is a well-known late complication of supracondylar fractures in children. In this retrospective study, the primary objective was to compare clinical and radiologic outcomes of lateral closing-wedge osteotomy with either internal fixation or external fixation in pediatric patients with cubitus varus deformities. MATERIALS AND METHODS: From 2010 to 2017, 35 consecutive patients with cubitus varus deformities secondary to supracondylar fractures were included in this study. After corrective osteotomy was performed via a limited lateral approach, the method of definitive fixation was chosen between internal and external. Retrospectively, patients who underwent external fixation on the lateral aspect of the elbow were defined as group I (n = 16) whereas patients with unilateral single-plate fixation were defined as group II (n = 19). The functional outcome was evaluated using the Mayo Elbow Performance Score and Flynn criteria. RESULTS: No significant difference in age was found between the 2 groups (P = .15). Significantly lower costs, a shorter operation duration, smaller scars, and a shorter time for plaster cast use postoperatively were found in group I (P < .001). No nonunion or failure of fixation was found. No significant difference was noted in postoperative elbow range of motion or Mayo Elbow Performance Score (P = .64). Both groups achieved satisfactory functional and cosmetic results. CONCLUSIONS: In pediatric patients with cubitus varus, both methods of fixation after lateral closing-wedge corrective osteotomy are reliable, with a low rate of complications and satisfactory functional results. External fixation is more advantageous in terms of easier preoperative planning, shorter operative times, lower costs, and easier postoperative fixation removal.


Assuntos
Articulação do Cotovelo/cirurgia , Fixação de Fratura/métodos , Fraturas do Úmero/complicações , Deformidades Articulares Adquiridas/cirurgia , Osteotomia/métodos , Amplitude de Movimento Articular/fisiologia , Estudos de Casos e Controles , Criança , Articulação do Cotovelo/diagnóstico por imagem , Articulação do Cotovelo/fisiopatologia , Feminino , Humanos , Fraturas do Úmero/diagnóstico , Fraturas do Úmero/cirurgia , Deformidades Articulares Adquiridas/diagnóstico , Deformidades Articulares Adquiridas/etiologia , Masculino , Período Pós-Operatório , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento
20.
Mol Carcinog ; 58(2): 270-278, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30334579

RESUMO

Cholangiocarcinoma (CCA) is a devastating disease with very poor prognosis due to late diagnosis and resistance to traditional chemotherapies and radiotherapies. Herein, thioacetamide (TAA)-induced rat CCA model and CGCCA cell line were used; we aim to study the cytogenetic features during tumoral development of CCA and uncover the mystery regarding carcinogenesis of CCA. The Array comparative genomic hybridization analysis, in silico method, gene knockdown, Western blot, cell count proliferation assay, clonogenecity assay, and IHC staining were applied in this study. Array comparative genomic hybridization analysis was performed on all different TAA-induced phases of rat tissues to reveal the certain pattern, +2q45, +Xq22, -12p12, have been identified for the tumor early stage, where involve the gene TNNI3K. In addition, 16 genes and 3 loci were associated with rapid tumor progression; JAK-STAT signaling pathway was highly correlated to late stage of CCA. In silico database was used to observe TNNI3K was highly express at tumor part compared with normal adjacent tissue in CCA patients from TCGA dataset. Furthermore, the growth of TNNI3K-knockdown SNU308 and HuCCT1 cells decreased when compared with cells transfected with an empty vector cell demonstrated by proliferation and colonogenecity assay. Besides, over expression of TNNI3K was especially confirmed on human CCA tumors and compared with the intrahepatic duct stone bile duct tissues and normal bile duct tissues (P < 0.001). Our findings might uncover the mystery regarding carcinogenesis of CCA, and provide the potential genetic mechanism to the clinicians some ideas for the patients' treatment.


Assuntos
Neoplasias dos Ductos Biliares/genética , Colangiocarcinoma/genética , MAP Quinase Quinase Quinases/genética , MAP Quinase Quinase Quinases/metabolismo , Tioacetamida/efeitos adversos , Regulação para Cima , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Neoplasias dos Ductos Biliares/induzido quimicamente , Neoplasias dos Ductos Biliares/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Sobrevivência Celular , Colangiocarcinoma/induzido quimicamente , Colangiocarcinoma/metabolismo , Hibridização Genômica Comparativa , Feminino , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Proteínas Serina-Treonina Quinases , Ratos , Transdução de Sinais , Adulto Jovem
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