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1.
Chemistry ; : e202400021, 2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38477386

RESUMO

The development of novel and effective drug delivery systems aimed at enhancing therapeutic profile and efficacy of therapeutic agents is a critical challenge in modern medicine. This study presents an intelligent drug delivery system based on self-assembled two-dimensional peptide nanosheets (2D PNSs). Leveraging the tunable properties of amino acid structures and sequences, we design a peptide with the sequence of Fmoc-FKKGSHC, which self-assembles into 2D PNSs with uniform structure, high biocompatibility, and excellent degradability. Covalent attachment of thiol-modified doxorubicin (DOX) drugs to 2D PNSs via disulfide bond results in the peptide-drug conjugates (PDCs), which is denoted as PNS-SS-DOX. Subsequently, the PDCs are encapsulated within the injectable, thermosensitive chitosan (CS) hydrogels for drug delivery. The designed drug delivery system demonstrates outstanding pH-responsiveness and sustained drug release capabilities, which are facilitated by the characteristics of the CS hydrogels. Meanwhile, the covalently linked disulfide bond within the PNS-SS-DOX is responsive to intracellular glutathione (GSH) within tumor cells, enabling controlled drug release and significantly inhibiting the cancer cell growth. This responsive peptide-drug conjugate based on a 2D peptide nanoplatform paves the way for the development of smart drug delivery systems and has bright prospects in the future biomedicine field.

2.
J Colloid Interface Sci ; 663: 111-122, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38394816

RESUMO

Fluorescent bioimaging and photothermal therapy (PTT) techniques have potential significance in cancer diagnosis and treatment and have been widely applied in biomedical and practical clinical trials. This study proposes the molecular design and biofabrication of a two-dimensional (2D) nanoplatform, exhibiting promising prospects for synergistic bioimaging and PTT of tumors. First, biocompatible 2D peptide nanosheets (PNSs) were designed and prepared through peptide self-assembly. These served as a support matrix for assembling polyethylene glycol-modified Ag2S quantum dots (PEG-Ag2SQDs) to form a 2D nanoplatform (PNS/PEG-Ag2SQDs) with unique fluorescent and photothermal properties. The designed 2D nanoplatform not only showed improved photothermal efficacy and an elevated photothermal conversion efficiency of 52.46 %, but also demonstrated significant lethality against tumors in both in vitro and in vivo cases. Additionally, it displays excellent imaging effects in the near-infrared II region, making it suitable for synergistic fluorescent imaging-guided PTT of tumors. This study not only provides a facile approach for devising and synthesizing 2D peptide assemblies but also presents new biomimetic strategies to create functional 2D organic/inorganic nanoplatforms for biomedical applications.


Assuntos
Nanopartículas , Neoplasias , Pontos Quânticos , Humanos , Fototerapia/métodos , Terapia Fototérmica , Nanopartículas/química , Biomimética , Neoplasias/diagnóstico por imagem , Neoplasias/terapia , Neoplasias/patologia , Peptídeos , Linhagem Celular Tumoral
3.
Dalton Trans ; 53(11): 5034-5042, 2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38374728

RESUMO

The construction and investigation of dual-functional coordination polymers (CPs) with proton conduction and luminescence sensing is of great significance in clean energy and agricultural monitoring fields. In this work, an Mn-based coordination polymer (Mn-CP), namely, [Mn0.5(HL)] (H2L = HOOCC6H4C6H4CH2PO(OH)OCH3), was hydrothermally synthesized. Mn-CP has a one-dimensional (1D) chain structure, in which uncoordinated -COOH groups can serve as potential sites for fluorescence sensing. Moreover, Mn-CP shows good water and pH stabilities, offering the feasibility for proton conduction and sensing applications. Mn-CP displays comparatively high proton conductivity of 1.07 × 10-4 S cm-1 at 368 K and 95% relative humidity (RH), which is promising for proton conduction materials. Moreover, it can serve as a repeatable, highly selective, and visualized fluorescence sensor for detecting oxytetracycline (OTC). More importantly, Mn-CP reveals an amazing quantitative sensing of OTC in actual samples such as seawater, aquaculture freshwater, soil infiltration solutions, and tap water. This work proves the excellent application potential of dual-functional CPs in the field of clean energy and environmental protection, especially for the fluorescence detection of antibiotics in aquaculture systems.

4.
J Mater Chem B ; 12(9): 2253-2273, 2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38375592

RESUMO

The injury of both central and peripheral nervous systems can result in neurological disorders and severe nervous diseases, which has been one of the challenges in the medical field. The use of peptide-based hydrogels for nerve repair and regeneration (NRR) provides a promising way for treating these problems, but the effects of the functions of peptide hydrogels on the NRR efficiency have been not understood clearly. In this review, we present recent advances in the material design, matrix fabrication, functional tailoring, and NRR applications of three types of peptide-based hydrogels, including pure peptide hydrogels, other component-functionalized peptide hydrogels, and peptide-modified polymer hydrogels. The case studies on the utilization of various peptide-based hydrogels for NRR are introduced and analyzed, in which the effects and mechanisms of the functions of hydrogels on NRR are illustrated specifically. In addition, the fabrication of medical NRR scaffolds and devices for pre-clinical application is demonstrated. Finally, we provide potential directions on the development of this promising topic. This comprehensive review could be valuable for readers to know the design and synthesis strategies of bioactive peptide hydrogels, as well as their functional tailoring, in order to promote their practical applications in tissue engineering, biomedical engineering, and materials science.


Assuntos
Hidrogéis , Procedimentos de Cirurgia Plástica , Hidrogéis/farmacologia , Hidrogéis/uso terapêutico , Engenharia Tecidual , Peptídeos/farmacologia , Engenharia Biomédica
5.
Sci Rep ; 13(1): 18232, 2023 10 25.
Artigo em Inglês | MEDLINE | ID: mdl-37880319

RESUMO

Liver ischemia/reperfusion (I/R) injury is a common injury after liver transplantation and hepatectomy. Skimmianine (Ski) has antibacterial, antiviral pharmacological effects. However, it is not clear whether Ski has a protective effect against liver I/R injury. In the present study, we established a mouse liver I/R model and an AML12 cell hypoxia-reoxygenation (H/R) model, both pretreated with different concentrations of Ski. Serum transaminase levels, necrotic liver area, cell viability, inflammatory factors, oxidative stress and apoptosis-related levels were measured to assess the protective effect of Ski against liver I/R injury. Western blotting was used to detect apoptosis-related proteins and PI3K-AKT pathway-related proteins. Mice and cells were also treated with PI3K inhibitor LY294002 to assess changes in indicators of liver injury. The results showed that Ski significantly reduced transaminase levels, liver necrosis area, oxidative stress, and apoptosis levels in mice with I/R. Ski also inhibited cell injury and apoptosis after H/R. Moreover, Ski activated phosphorylation of PI3K-AKT pathway-related proteins after liver I/R and cell H/R. Importantly, the PI3K inhibitor LY294002 effectively reversed the alleviation of I/R injury caused by Ski. These results confirm that Ski exerts a protective effect against liver I/R injury through activation of the PI3K-AKT pathway.


Assuntos
Proteínas Proto-Oncogênicas c-akt , Traumatismo por Reperfusão , Camundongos , Animais , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Transdução de Sinais , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/metabolismo , Estresse Oxidativo , Fígado/metabolismo , Inflamação/metabolismo , Apoptose , Transaminases/metabolismo
6.
Inorg Chem ; 62(32): 12730-12740, 2023 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-37529894

RESUMO

The construction of attractive dual-functional lanthanide-based metal-organic frameworks (Ln-MOFs) with ratiometric fluorescent detection and proton conductivity is significant and challenging. Herein, a three-dimensional (3D) Eu-MOF, namely, [Eu4(HL)2(SBA)4(H2O)6]·9H2O, has been hydrothermally synthesized with a dual-ligand strategy, using (4-carboxypiperidyl)-N-methylenephosphonic acid (H3L = H2O3PCH2-NC5H9-COOH) and 4-sulfobenzoic acid monopotassium salt (KHSBA = KO3SC6H4COOH) as organic linkers. Eu-MOF showed ratiometric fluorescent broad-spectrum sensing of benzophenone-like ultraviolet filters (BP-like UVFs) with satisfactory sensitivity, selectivity, and low limits of detection in water/ethanol (1:1, v/v) solutions and real urine systems. A portable test paper was prepared for the convenience of actual detection. The potential sensing mechanisms were thoroughly analyzed by diversified experiments. The synergistic effect of the forbidden energy transfer from the ligand to Eu3+, the internal filtration effect (IFE), the formation of a complex, and weak interactions between the KHSBA ligand and BP-like UVFs is responsible for the ratiometric sensing effect. Meanwhile, Eu-MOF displayed relatively high proton conductivity of 2.60 × 10-4 S cm-1 at 368 K and 95% relative humidity (RH), making it a potential material for proton conduction. This work provides valuable guidance for the facile and effective design and construction of multifunctional Ln-MOFs with promising performance.

7.
J Nanobiotechnology ; 21(1): 238, 2023 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-37488557

RESUMO

Functional hydrogels show potential application in repairing spinal cord injury (SCI) due to their unique chemical, physical, and biological properties and functions. In this comprehensive review, we present recent advance in the material design, functional regulation, and SCI repair applications of bioactive hydrogels. Different from previously released reviews on hydrogels and three-dimensional scaffolds for the SCI repair, this work focuses on the strategies for material design and biologically functional regulation of hydrogels, specifically aiming to show how these significant efforts can promoting the repairing performance of SCI. We demonstrate various methods and techniques for the fabrication of bioactive hydrogels with the biological components such as DNA, proteins, peptides, biomass polysaccharides, and biopolymers to obtain unique biological properties of hydrogels, including the cell biocompatibility, self-healing, anti-bacterial activity, injectability, bio-adhesion, bio-degradation, and other multi-functions for repairing SCI. The functional regulation of bioactive hydrogels with drugs/growth factors, polymers, nanoparticles, one-dimensional materials, and two-dimensional materials for highly effective treating SCI are introduced and discussed in detail. This work shows new viewpoints and ideas on the design and synthesis of bioactive hydrogels with the state-of-the-art knowledges of materials science and nanotechnology, and will bridge the connection of materials science and biomedicine, and further inspire clinical potential of bioactive hydrogels in biomedical fields.


Assuntos
Nanopartículas , Traumatismos da Medula Espinal , Regeneração da Medula Espinal , Humanos , Biomassa , Hidrogéis
8.
Risk Manag Healthc Policy ; 16: 1259-1271, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37456825

RESUMO

Purpose: The AJCC (the American Joint Committee on Cancer) ypTNM (post-neoadjuvant pathologic stage group) staging was established based on patients with lymphadenectomy scope less than D2 and did not include ypT0N0 patients with pathologically complete response (PCR). The purpose of this study was to construct a survival predictive model for gastric cancer patients after neoadjuvant chemotherapy and gastrectomy combined with D2 lymphadenectomy. Patients and Methods: The multicenter data of 838 gastric cancer patients who received neoadjuvant chemotherapy and gastrectomy combined with D2 lymphadenectomy were analyzed retrospectively. These dual center patients were divided into training (n = 671, the Affiliated Hospital of Qingdao University) and validation (n = 167, Qingdao West Coast New Area Central Hospital) cohorts. Based on training cohort, univariate and multivariable COX regression analyses were performed to select the clinicopathological characteristics significantly correlating with overall survival and construct a nomogram. Based on training and validation cohorts, the distinguishing and calibrating capabilities of nomogram was evaluated by the receiver operating characteristic (ROC) curve, Harrell's concordance index (C-index), decision curve analysis (DCA) curve and calibration curve. Results: Platelet-to-lymphocyte ratio (PLR), pathologic stage after neoadjuvant treatment: ypT and ypN stage, tumor regression grade (TRG) became independent variables intimately related to the prognosis and was used to construct nomograms of 3/5-year prognosis. The nomograms showed an accuracy in predicting OS (overall survival) rate, with area under the ROC curve (AUC) of 0.818 (95% CI = 0.753~0.883) and C-index of 0.801 (95% CI = 0.744~0.858) in validation cohort. Calibration curves showed satisfactory agreement between nomogram prediction and actual result, and DCA curves indicated the large positive net benefit and excellent clinical usefulness of nomogram. Conclusion: This study successfully developed a nomogram to predict overall survival of gastric cancer patients after neoadjuvant chemotherapy and gastrectomy combined with D2 lymphadenectomy, which might have excellent predictive performance and clinical application value.

9.
Dalton Trans ; 52(25): 8558-8566, 2023 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-37288585

RESUMO

By selecting a bisphosphonic ligand H4L (H4L = 4-F-C6H4CH2N(CH2PO3H2)2) and a coligand oxalate (H2C2O4), three isostructural lanthanide metal-organic frameworks (Ln-MOFs) with a 2D layer structure, [Ln(H3L)(C2O4)]·2H2O (Ln = Eu (1), Gd (2), or Tb (3)), were hydrothermally prepared. By tuning the molar ratio of Eu3+, Gd3+, and Tb3+ in the above reactions, six bimetallic or trimetallic doped Ln-MOFs (EuxTb1-x (x = 0.02 (4), 0.04 (5), and 0.06 (6)), Gd0.94Eu0.06 (7), Gd0.96Tb0.04 (8) and Gd0.95Tb0.03Eu0.02 (9)) were obtained. The powder X-ray diffraction (PXRD) patterns of doped Ln-MOFs 4-9 show that they are isomorphous with 1-3. The bimetallic doped Ln-MOFs show a gradual variation of luminous colors between yellow-green, yellow, orange, pink, and light blue. Meanwhile, the trimetallic doped Gd0.95Tb0.03Eu0.02 Ln-MOF (9) displays near white-light emission with a quantum yield of 11.39%. Interestingly, the luminous inks of 1-9 are invisible and color tunable, which makes it possible to promote their anti-counterfeiting applications. Additionally, 3 displays good thermal, water, and pH stabilities, which provides the feasibility for its sensing application. The luminescence sensing experiments show that 3 can serve as a highly selective, reusable, and ratiometric luminescent sensor of sulfamethazine (SMZ). Moreover, 3 shows an excellent SMZ detection performance in real samples, such as mariculture water and real urine. Owing to the visible variation of the response signal under a UV lamp, portable SMZ test paper was prepared.

10.
Dalton Trans ; 52(16): 5202-5211, 2023 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-36970992

RESUMO

Developing high-accuracy luminescent sensors for detecting emerging environmental pollutants is of great importance and is still a challenge. Utilizing a 4-carboxyphenylphosphonic acid (H3pbc) ligand, a novel one-dimensional (1D) Zn-based coordination polymer with the formula [Zn2(Hpbc)2(2,2'-bipy)(H2O)]·H2O (Zn-CP, H3pbc = 4-HOOCC6H4PO3H2, 2,2'-bipy = 2,2'-bipyridine) has been hydrothermally synthesized. Each of the 1D chains was linked via π-π stacking interactions and formed a supramolecular framework. Furthermore, due to the existence of uncoordinated -COOH groups, the terbium-functionalized hybrid (Tb3+@Zn-CP) was prepared by introducing Tb3+ ions into the structure through coordinated postsynthetic modification (PSM). Tb3+@Zn-CP shows the characteristic emission of Tb3+ ions due to the "antenna effect" of the H3pbc ligand. Based on the excellent luminescence properties and structural stabilities of Zn-CP and Tb3+@Zn-CP, they can be used as highly sensitive and selective luminescent probes of the UV filter BP (benzophenone) depending on multiquenching effects. In addition, their obvious color change can be easily distinguished by the naked eye under ultraviolet light, which was successfully used in the preparation of portable BP test paper. More importantly, Tb3+@Zn-CP is the first example of CPs as a ratiometric luminescent sensor for BP. This work provides a novel strategy for the construction of ratiometric luminescent probes of BP-type UVFs through coordinated postsynthetic modification.

11.
Inorg Chem ; 61(49): 20111-20122, 2022 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-36424127

RESUMO

Construction and investigation of dual-functional metal-organic frameworks (MOFs) with luminescent sensing and proton conduction provide widespread applications in clean energy and environmental monitoring fields. By selecting a phosphonic acid ligand 4-pyridyl-CH2N(CH2PO3H2)2 (H4L) and coligand 2,2'-biimidazole (H2biim), two cadmium-based MOFs [Cd1.5(HL)(H2biim)0.5] (1) and (H4biim)0.5·[Cd2(L)(H2biim)Cl] (2) with different structures and properties have been hydrothermally synthesized by controlling reaction temperature. Based on the excellent thermal and chemical stabilities, and good luminescent stabilities in water solution, 1 and 2 can serve as luminescent sensors of chloramphenicol (CAP) with different quenching constant (KSV) values and detection limits (LODs) in water, simulated environmental system, and real fish water system. Meanwhile, different sensing effects and possible sensing mechanisms are analyzed in detail. Moreover, 1 and 2 can also serve as good proton-conducting materials. The proton conductivities can reach up to 1.41 × 10-4 S cm-1 for 1 and 1.02 × 10-3 S cm-1 for 2 at 368 K and 95% relative humidity (RH). Among them, 2 shows better luminescent sensing and proton conduction performance than 1, which indicates that different crystal structures have a great impact on the properties of MOFs. Through the discussion of the relationship between structures and properties in detail, the possible reasons for the differences in properties are obtained, which can provide theoretical guidance for the rational design of this kind of dual-functional MOFs in the future.


Assuntos
Estruturas Metalorgânicas , Animais , Prótons , Antibacterianos , Cádmio , Água
12.
Sci Rep ; 12(1): 13329, 2022 08 03.
Artigo em Inglês | MEDLINE | ID: mdl-35922531

RESUMO

Six members of the gasdermin family are involved in various biological functions in malignant tumors. The present study aimed to perform a comprehensive analysis of gasdermin family genes in pan-cancer. Raw data was acquired from the genotype-tissue expression (GTEx) and the Cancer Genome Atlas. High inter-tumor heterogeneity in the expression between paracancerous and tumor tissues was observed across cancers. Survival analysis confirmed that the risk or protective effects of gasdermin family members on prognosis depended on the cancer types. The mutation frequency appeared to be high, and the mutation group had a worse prognosis. Besides, gasdermin family genes were associated with immune infiltrate subtypes, stromal and immune cell infiltration levels, TMB, MSI, immune checkpoint gene expression, and tumor stemness scores. Moreover, gasdermin family gene expressions affected the expressions of MMR genes and methyltransferases and could predict cancer cells sensitivity to chemotherapeutic drugs. Subsequently, the findings were double-checked in LIHC and PAAD. GSEA results indicated the gasdermin family genes mainly involved in tumor metabolism and immune microenvironment remodeling related signaling pathways. In conclusion, our findings confirmed that gasdermin family genes were potential therapeutic cancer targets in pan-cancer.


Assuntos
Biomarcadores Tumorais , Neoplasias , Humanos , Biomarcadores Tumorais/genética , Neoplasias/genética , Neoplasias/terapia , Prognóstico , Análise de Sobrevida , Microambiente Tumoral/genética
13.
Spine (Phila Pa 1976) ; 47(5): E203-E213, 2022 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-34431832

RESUMO

STUDY DESIGN: In vitro experimental study. OBJECTIVE: To establish an axial impact injury model of intervertebral disc (IVD) and to investigate if a single impact injury without endplate structural disruption could initiate intervertebral disc degeneration (IDD), and what is the roles of Piezo1 in this process. SUMMARY OF BACKGROUND DATA: Although IDD process has been confirmed to be associated with structural failures such as endplate fractures, whether a single impact injury of the endplates without structural disruption could initiate IDD remains controversial. Previous studies reported that Piezo1 mediated inflammation participated in the progression of IDD induced by mechanical stretch; however, the roles of Piezo1 in IVD impact injury remain unknown. METHODS: Rats spinal segments were randomly assigned into Control, Low, and High Impact groups, which were subjected to pure axial impact loading using a custom-made apparatus, and cultured for 14 days. The degenerative process was investigated by using histomorphology, real-time Polymerase Chain Reaction(PCR), western-blot, immunofluorescence, and energy metabolism of IVD cell. The effects of Piezo1 were investigated by using siRNA transfection, real-time PCR, western-blot, and immunofluorescence. RESULTS: The discs in both of the impact groups presented degenerative changes after 14 days, which showed significant up-regulation of Piezo1, NLRP3 inflammasome, the catabolic (MMP-9, MMP-13), and pro-inflammatory gene (IL-1ß) expression than that of the control group (P < 0.05), accompanied by significantly increased release of ATP, lactate, nitric oxide (NO), and glucose consumption of IVD cells at first 7 days. Silencing Piezo1 reduced the activation of NLRP3 inflammasome and IL-1ß expression in the nucleus pulposus induced by impact injury. CONCLUSION: It demonstrated that not only fracture of the endplate but also a single impact injury without structural impairment could also initiate IDD, which might be mediated by activation of Piezo1 induced inflammation and abnormal energy metabolism of IVD cells.Level of Evidence: N/A.


Assuntos
Degeneração do Disco Intervertebral , Disco Intervertebral , Núcleo Pulposo , Traumatismos da Coluna Vertebral , Animais , Inflamação/genética , Degeneração do Disco Intervertebral/genética , Ratos
14.
J Sep Sci ; 45(3): 664-676, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34813681

RESUMO

A new rapid ultra-high-performance liquid chromatography coupled with linear trap quadrupole orbitrap mass spectrometry method was established for the qualitative analysis of absorbed ingredients and metabolites of Zhimu-Huangbai herb pair, which is used to treat type 2 diabetes mellitus. A total of 16 absorbed ingredients and 11 metabolites were identified in normal and type 2 diabetes mellitus rats, respectively. Such findings indicated that the diabetic model had no effect on the type of components in plasma. Seven absorbed ingredients and 11 metabolites were first identified after the oral administration of Zhimu-Huangbai herb pair. Thereafter, ultra-high-performance liquid chromatography coupled with linear trap quadrupole orbitrap mass spectrometry and liquid chromatography-API4000+ triple quadrupole mass spectrometer methods were established and validated for pharmacokinetic comparative studies of seven major bioactive components in normal and type 2 diabetes mellitus rats. Partial pharmacokinetic parameters in the plasma of type 2 diabetes mellitus rats were significantly different from those in normal rats. To our knowledge, this is the first comparison of absorbed ingredients and metabolites of Zhimu-Huangbai herb pair, and its use in pharmacokinetic studies between normal and type 2 diabetes mellitus rats. Ultimately, our findings provide insights into the clinical usage of Zhimu-Huangbai herb pair.


Assuntos
Diabetes Mellitus Tipo 2 , Medicamentos de Ervas Chinesas , Animais , Cromatografia Líquida de Alta Pressão/métodos , Cromatografia Líquida/métodos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Medicamentos de Ervas Chinesas/química , Ratos , Espectrometria de Massas em Tandem/métodos
15.
Front Med (Lausanne) ; 8: 762570, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34970559

RESUMO

Objective: The present study aimed to establish a prognostic signature based on the autophagy-related long non-coding RNAs (lncRNAs) analysis in patients with hepatocellular carcinoma (HCC). Methods: Patients with HCC from The Cancer Genome Atlas (TCGA) were taken as the training cohort, and patients from the International Cancer Genome Consortium (ICGC) were treated as the validation cohort. Autophagy-related lncRNAs were obtained via a co-expression network analysis. According to univariate and multivariate analyses, a multigene prognostic signature was constructed in the training cohort. The predictive power of the signature was confirmed in both cohorts. The detailed functions were investigated using functional analysis. The single-sample gene set enrichment analysis (ssGSEA) score was used to evaluate the tumor microenvironment. The expression levels of immunotherapy and targeted therapy targets between the two risk groups were compared. Finally, a nomogram was constructed by integrating clinicopathological parameters with independently predictive value and the risk score. Results: Four autophagy-related lncRNAs were identified to establish a prognostic signature, which separated patients into high- and low-risk groups. Survival analysis showed that patients in the high-risk group had a shorter survival time in both cohorts. A time-independent receiver-operating characteristic (ROC) curve and principal component analysis (PCA) confirmed that the prognostic signature had a robust predictive power and reliability in both cohorts. Functional analysis indicated that the expressed genes in the high-risk group are mainly enriched in autophagy- and cancer-related pathways. ssGSEA revealed that the different risk groups were associated with the tumor microenvironment. Moreover, the different risk groups had positive correlations with the expressions of specific mutant genes. Multivariate analysis showed that the risk score also exhibited excellent predictive power irrespective of clinicopathological characteristics in both cohorts. A nomogram was established. The nomogram showed good discrimination, with Harrell's concordance index (C-index) of 0.739 and good calibration. Conclusion: The four autophagy-related lncRNAs could be used as biological biomarkers and therapeutic targets. The prognostic signature and nomogram might aid clinicians in individual treatment optimization and clinical decision-making for patients with HCC.

16.
Inorg Chem ; 60(22): 17303-17314, 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34699193

RESUMO

It remains a challenge to exploit dual-functional metal-organic frameworks (MOFs) for applications, including luminescence detection and proton conduction. With the deliberate selection of the bifunctional organic ligand 5-sulfoisophthalic acid monosodium salt (NaH2bts), and the phosphonic acid ligand N,N'-piperazine (bismethylenephosphonic acid; H4L), a robust three-dimensional (3D) noninterpenetrating dual-functional MOF, [Tb(H2L)(H2bts)(H2O)]·H2O (1), has been synthesized hydrothermally. On the basis of the excellent thermal and chemical as well as superior luminescence stabilities in water and solutions with different pHs, 1 can serve as the simple, rapid, and highly selective and sensitive luminescence detection of the carcinoid biomarkers 5-hydroxytryptamine (HT) and its metabolite 5-hydroxyindole-3-acetic acid (HIAA) with detection limits of nanomolar magnitude in water and in simulated blood plasma and urine systems. Due to the change in the signals that could be readily differentiated by the naked eye under a UV lamp, a portable test paper has been developed. The probable quenching mechanisms are discussed in detail. In addition, a great number of hydrogen-bonding networks are formed among the uncoordinated carboxylic oxygen atoms, sulfonate oxygen atoms, protonated nitrogen atoms, and water molecules, which provide potential proton-hopping sites for proton conduction, leading to a maximum proton conductivity of 2.3 × 10-4 S cm-1 at 368 K and 95% relative humidity. The above results suggest that rationally designed dual-functional MOFs can open an avenue for the development of occupational diagnostic tools and alternative energy technology.


Assuntos
Tumor Carcinoide/química , Luminescência , Estruturas Metalorgânicas/química , Prótons , Biomarcadores/análise , Estruturas Metalorgânicas/síntese química , Modelos Moleculares
17.
Sci Rep ; 11(1): 13814, 2021 07 05.
Artigo em Inglês | MEDLINE | ID: mdl-34226605

RESUMO

The study aimed to evaluate the prognostic significance of preoperative systemic inflammatory biomarkers including albumin to globulin ratio (AGR), neutrophil to lymphocyte ratio (NLR), lymphocyte to monocyte ratio (LMR), and platelet to lymphocyte ratio (PLR) and establish a nomogram in hepatocellular carcinoma (HCC) patients after microwave ablation (MWA). 192 HCC patients receiving MWA as initial therapy from the first ward of hepatobiliary surgery were classified as training cohort. Whereas, 84 patients from the second of hepatobiliary surgery were classified as validation cohort. Kaplan-Meier (KM) method and univariate analyses showed that AGR, NLR, LMR, and PLR were significantly associated with OS in the training cohort. Multivariate analysis including clinicopathologic features screened out independent predictors including ascites, tumor size, cancer embolus, AGR, and PLR. Based on those variables, a nomogram for predicting OS was established. The C-index was 0.794 in the training cohort and 0.772 in the validation cohort. Calibration plots identified the nomogram performed well with an ideal model. Compared with Barcelona Clinic Liver Cancer (BCLC) staging system and simple tumor size, the nomogram showed better predictive ability. Besides, the nomogram discovered the highest diagnostic accuracy in predicting postoperative clinical outcome than the combination of the present models with tumor size. In conclusion, the constructed nomogram could accurately predict individualized survival probability and might support clinician in individual treatment optimization and clinical decision-making.


Assuntos
Biomarcadores Tumorais/sangue , Carcinoma Hepatocelular/terapia , Inflamação/sangue , Neoplasias Hepáticas/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Plaquetas/metabolismo , Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/patologia , Intervalo Livre de Doença , Feminino , Humanos , Inflamação/complicações , Inflamação/patologia , Estimativa de Kaplan-Meier , Contagem de Leucócitos , Neoplasias Hepáticas/patologia , Linfócitos/patologia , Masculino , Micro-Ondas/uso terapêutico , Pessoa de Meia-Idade , Monócitos , Neutrófilos/patologia , Nomogramas , Contagem de Plaquetas , Cuidados Pré-Operatórios , Prognóstico , Ablação por Radiofrequência/métodos
18.
J Musculoskelet Neuronal Interact ; 21(2): 308-316, 2021 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-34059576

RESUMO

OBJECTIVES: To explore the expression and correlation of Omentin-1 and miR-502-3p in serum of patients with osteoporotic fracture (OPF). METHODS: Sixty OPF patients diagnosed and treated in our hospital from June 2018 to December 2019 were included in group A. Fifty-six osteoporosis patients without fractures were included in group B. Omentin-1 and miR-502-3p levels were detected by enzyme-linked immunosorbent assay (ELISA) and real-time quantitative PCR (qRT-PCR). Their predictive value for diagnostic efficiency was assessed by ROC curve. Spearman's rank correlation test was used for correlation analysis. The risk factors related to the prognosis of OPF were analyzed by Logistic univariate and multivariate analysis. RESULTS: The expression of Omentin-1 and miR-502-3p in group A was markedly lower than in group B (P<0.001). Spearman correlation analysis showed that in OPF, there was a negative correlation between serum Omentin-1 and TNF-α (r=0.8579, P<0.001), a negative correlation between serum miR-502-3p and TNF-α (r= 0.8653, P<0.001), and a positive correlation between serum Omentin-1 and miR-502-3p (r= 0.8764, P<0.001). CONCLUSIONS: Omentin-1 and miR-502-3p were down-regulated in serum of patients with OPF, both of which could be used as potential biomarkers for the diagnosis and disease evaluation of OPF.


Assuntos
MicroRNAs/genética , Fraturas por Osteoporose , Citocinas , Proteínas Ligadas por GPI , Humanos , Lectinas , Fraturas por Osteoporose/genética , Prognóstico , Curva ROC , Fator de Necrose Tumoral alfa
19.
Dalton Trans ; 50(18): 6152-6160, 2021 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-33885683

RESUMO

Metal-organic framework (MOF) materials have been extensively incorporated with inorganic semiconductor photocatalysts to improve their photocatalytic activity through an efficient charge transfer process across their heterointerface. In this work, octahedral UiO-66-NH2 MOFs with edge-lengths of 110-330 nm are uniformly decorated on the surface of TiO2 electrospun nanofibers by a traditional solvothermal method combined with activation pretreatment. Before the solvothermal growth of UiO-66-NH2, the TiO2 electrospun nanofibers were activated in NaOH solution to etch the TiO2 surface for allowing the exposure of lattice oxygen. The exposed lattice oxygen on the TiO2 surface could interact with the MOF precursor of Zr4+ ions, thus enabling octahedral UiO-66-NH2 to grow uniformly on the surface of TiO2 nanofibers with an intimate Ti-O-Zr hetero-interface. Such an intimate hetero-interface provides an effective channel for boosting the electron transfer between UiO-66-NH2 and TiO2 in their heterostructure. Thus, the UiO-66-NH2/TiO2(anatase) heterostructures exhibited enhanced photocatalytic activity for H2 production as compared to either TiO2(anatase) nanofibers or UiO-66-NH2 nanooctahedra in the presence of Rhodamine B (RhB) as a sensitizer under visible light irradiation. In particular, the decoration of UiO-66-NH2 nanooctahedra on anatase/rutile mixed TiO2 nanofibers could induce further enhancement of the photocatalytic H2 production. The enhanced photocatalytic activity is attributed to the multi-step continuous interfacial transfer of photoinduced electrons with the way of RhB → UiO-66-NH2 → TiO2(anatase) → TiO2(rutile).

20.
Medicine (Baltimore) ; 99(31): e21021, 2020 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-32756087

RESUMO

The purpose of this study was to investigate the potential prognostic value of preoperative lymphocyte-to-monocyte ratio (LMR) and establishment of a prognostic nomogram in post surgical patients with gallbladder carcinoma (GBC).Receiver operating characteristic curve analysis was performed to determine the optimal cut-off value of LMR. The correlation between preoperative LMR and overall survival (OS) was analyzed using univariate and multivariate Cox regression analyses. A relevant prognostic nomogram was established.Three hundred fifteen GBC patients were retrospectively enrolled. Based on receiver operating characteristic curve analysis, the optimal cutoff value of LMR was 2.685. Patients were categorized into high-LMR group (n = 143) or low-LMR group (n = 172). Low-LMR value was significantly associated with elderly age, advanced tumor, and the performance of a palliative cholecystectomy. The results of the univariate and multivariate analyses eliminated the degree of tumor differentiation, tumor-node-metastasis stages, surgery types, and LMR as independent predictors of OS. Based on those independent predictors, a predictive nomogram for OS was generated with an accuracy of 0.848.Based on our findings, the predictive nomogram should be included in the routine assessment of GBC patients.


Assuntos
Neoplasias da Vesícula Biliar/diagnóstico , Contagem de Leucócitos , Contagem de Linfócitos , Monócitos , Nomogramas , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Vesícula Biliar/mortalidade , Neoplasias da Vesícula Biliar/patologia , Neoplasias da Vesícula Biliar/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Prognóstico , Curva ROC , Reprodutibilidade dos Testes , Estudos Retrospectivos , Análise de Sobrevida
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