Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 235
Filtrar
Mais filtros

Tipo de documento
Intervalo de ano de publicação
1.
Chembiochem ; 25(6): e202300679, 2024 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-38205937

RESUMO

The connection between 3d (Cu) and 4d (Mo) via the "Mo-S-Cu" unit is called Mo-Cu antagonism. Biology offers case studies of such interactions in metalloproteins such as Mo/Cu-CO Dehydrogenases (Mo/Cu-CODH), and Mo/Cu Orange Protein (Mo/Cu-ORP). The CODH significantly maintains the CO level in the atmosphere below the toxic level by converting it to non-toxic CO2 for respiring organisms. Several models were synthesized to understand the structure-function relationship of these native enzymes. However, this interaction was first observed in ruminants, and they convert molybdate (MoO4 2- ) into tetrathiomolybdate (MoS4 2- ; TTM), reacting with cellular Cu to yield biological unavailable Mo/S/Cu cluster, then developing Cu-deficiency diseases. These findings inspire the use of TTM as a Cu-sequester drug, especially for treating Cu-dependent human diseases such as Wilson diseases (WD) and cancer. It is well known that a balanced Cu homeostasis is essential for a wide range of biological processes, but negative consequence leads to cell toxicity. Therefore, this review aims to connect the Mo-Cu antagonism in metalloproteins and anti-copper therapy.


Assuntos
Cobre , Metaloproteínas , Humanos , Cobre/metabolismo , Molibdênio/farmacologia , Molibdênio/uso terapêutico
2.
J Nanobiotechnology ; 22(1): 515, 2024 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-39198894

RESUMO

Recent advancements in cancer research have led to the generation of innovative nanomaterials for improved diagnostic and therapeutic strategies. Despite the proven potential of two-dimensional (2D) molybdenum disulfide (MoS2) as a versatile platform in biomedical applications, few review articles have focused on MoS2-based platforms for cancer theranostics. This review aims to fill this gap by providing a comprehensive overview of the latest developments in 2D MoS2 cancer theranostics and emerging strategies in this field. This review highlights the potential applications of 2D MoS2 in single-model imaging and therapy, including fluorescence imaging, photoacoustic imaging, photothermal therapy, and catalytic therapy. This review further classifies the potential of 2D MoS2 in multimodal imaging for diagnostic and synergistic theranostic platforms. In particular, this review underscores the progress of 2D MoS2 as an integrated drug delivery system, covering a broad spectrum of therapeutic strategies from chemotherapy and gene therapy to immunotherapy and photodynamic therapy. Finally, this review discusses the current challenges and future perspectives in meeting the diverse demands of advanced cancer diagnostic and theranostic applications.


Assuntos
Dissulfetos , Molibdênio , Neoplasias , Nanomedicina Teranóstica , Molibdênio/química , Molibdênio/uso terapêutico , Humanos , Dissulfetos/química , Nanomedicina Teranóstica/métodos , Neoplasias/terapia , Neoplasias/diagnóstico por imagem , Animais , Sistemas de Liberação de Medicamentos/métodos , Técnicas Fotoacústicas/métodos , Nanoestruturas/química , Nanoestruturas/uso terapêutico , Imagem Multimodal/métodos
3.
J Nanobiotechnology ; 22(1): 85, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38429826

RESUMO

BACKGROUND: Impaired collateral formation is a major factor contributing to poor prognosis in type 2 diabetes mellitus (T2DM) patients with atherosclerotic cardiovascular disease. However, the current pharmacological treatments for improving collateral formation remain unsatisfactory. The induction of endothelial autophagy and the elimination of reactive oxygen species (ROS) represent potential therapeutic targets for enhancing endothelial angiogenesis and facilitating collateral formation. This study investigates the potential of molybdenum disulfide nanodots (MoS2 NDs) for enhancing collateral formation and improving prognosis. RESULTS: Our study shows that MoS2 NDs significantly enhance collateral formation in ischemic tissues of diabetic mice, improving effective blood resupply. Additionally, MoS2 NDs boost the proliferation, migration, and tube formation of endothelial cells under high glucose/hypoxia conditions in vitro. Mechanistically, the beneficial effects of MoS2 NDs on collateral formation not only depend on their known scavenging properties of ROS (H2O2, •O2-, and •OH) but also primarily involve a molecular pathway, cAMP/PKA-NR4A2, which promotes autophagy and contributes to mitigating damage in diabetic endothelial cells. CONCLUSIONS: Overall, this study investigated the specific mechanism by which MoS2 NDs mediated autophagy activation and highlighted the synergy between autophagy activation and antioxidation, thus suggesting that an economic and biocompatible nano-agent with dual therapeutic functions is highly preferable for promoting collateral formation in a diabetic context, thus, highlighting their therapeutic potential.


Assuntos
Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Humanos , Camundongos , Animais , Diabetes Mellitus Tipo 2/tratamento farmacológico , Espécies Reativas de Oxigênio/metabolismo , Células Endoteliais/metabolismo , Molibdênio/farmacologia , Molibdênio/uso terapêutico , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/metabolismo , Peróxido de Hidrogênio/metabolismo , Autofagia
4.
J Transl Med ; 21(1): 351, 2023 05 27.
Artigo em Inglês | MEDLINE | ID: mdl-37244993

RESUMO

The current ageing trend of the world population has, in part, accounted for Alzheimer disease (AD) being a public health issue in recent times. Although some progress has been made in clarifying AD-related pathophysiological mechanisms, effective intervention is still elusive. Biometals are indispensable to normal physiological functions of the human body-for example, neurogenesis and metabolism. However, their association with AD remains highly controversial. Copper (Cu) and zinc (Zn) are biometals that have been investigated at great length in relation to neurodegeneration, whereas less attention has been afforded to other trace biometals, such as molybdenum (Mo), and iodine. Given the above context, we reviewed the limited number of studies that have evidenced various effects following the usage of these two biometals in different investigative models of AD. Revisiting these biometals via thorough investigations, along with their biological mechanisms may present a solid foundation for not only the development of effective interventions, but also as diagnostic agents for AD.


Assuntos
Doença de Alzheimer , Iodo , Oligoelementos , Humanos , Oligoelementos/metabolismo , Oligoelementos/uso terapêutico , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/terapia , Molibdênio/uso terapêutico , Iodo/uso terapêutico , Zinco/uso terapêutico , Cobre/metabolismo , Cobre/uso terapêutico
5.
Pharmacol Res ; 192: 106768, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37061147

RESUMO

Osteoarthritis (OA) is one of the most prevalent musculoskeletal disorders globally, and treating OA remains a significant challenge. Currently, pharmacological treatments primarily aim to alleviate the OA symptoms associated with inflammation and pain, and no disease-modifying therapies are available to delay OA development and progression. Reactive oxygen species (ROS) play an essential role in OA development and progression, which are a promising target for curing OA. In this study, it was found that photothermal properties of near-infrared (NIR) irradiation enhanced the ROS scavenging activity of molybdenum-based polyoxometalate (POM) nanoclusters. Because of enhanced ROS scavenging, NIR-responsive POM nanoclusters were developed as novel excellent nano-antioxidants for OA protection. The results demonstrated that NIR-responsive POM exhibited outstanding antioxidant activity and superexcellent anti-inflammatory effects, which could effectively alleviate the clinical symptoms of OA mice, diminish inflammatory cytokines, reduce catabolic proteases, and mitigate the progression of OA. Meanwhile, the local treatment had no side effects on normal tissues. Thus, this study pioneered the application of POM for alleviating OA with expected safety and efficiency.


Assuntos
Molibdênio , Osteoartrite , Camundongos , Animais , Molibdênio/uso terapêutico , Espécies Reativas de Oxigênio/metabolismo , Osteoartrite/tratamento farmacológico , Inflamação , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico
6.
J Nanobiotechnology ; 20(1): 216, 2022 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-35524267

RESUMO

Blockade of programmed cell death 1 ligand (PD-L1) has been used to treat triple-negative breast cancer (TNBC), and various strategies are under investigation to improve the treatment response rate. Inhibition of glutamine metabolism can reduce the massive consumption of glutamine by tumor cells and meet the demand for glutamine by lymphocytes in tumors, thereby improving the anti-tumor effect on the PD-L1 blockade therapy. Here, molybdenum disulfide (MoS2) was employed to simultaneously deliver anti-PDL1 antibody (aPDL1) and V9302 to boost the anti-tumor immune response in TNBC cells. The characterization results show that MoS2 has a dispersed lamellar structure with a size of about 181 nm and a size of 232 nm after poly (L-lysine) (PLL) modification, with high stability and biocompatibility. The loading capacity of aPDL1 and V9302 are 3.84% and 24.76%, respectively. V9302 loaded MoS2 (MoS2-V9302) can effectively kill 4T1 cells and significantly reduce glutamine uptake of tumor cells. It slightly increases CD8+ cells in the tumor and promotes CD8+ cells from the tumor edge into the tumor core. In vivo studies demonstrate that the combination of aPDL1 and V9302 (MoS2-aPDL1-V9302) can strongly inhibit the growth of TNBC 4T1 tumors. Interestingly, after the treatment of MoS2-aPDL1-V9302, glutamine levels in tumor interstitial fluid increased. Subsequently, subtypes of cytotoxic T cells (CD8+) in the tumors were analyzed according to two markers of T cell activation, CD69, and CD25, and the results reveal a marked increase in the proportion of activated T cells. The levels of cytokines in the corresponding tumor interstitial fluid are also significantly increased. Additionally, during the treatment, the body weights of the mice remain stable, the main indicators of liver and kidney function in the blood do not increase significantly, and there are no obvious lesions in the main organs, indicating low systemic toxicity. In conclusion, our study provides new insights into glutamine metabolism in the tumor microenvironment affects immune checkpoint blockade therapy in TNBC, and highlights the potential clinical implications of combining glutamine metabolism inhibition with immune checkpoint blockade in the treatment of TNBC.


Assuntos
Neoplasias de Mama Triplo Negativas , Animais , Antígeno B7-H1/metabolismo , Linhagem Celular Tumoral , Glutamina , Humanos , Inibidores de Checkpoint Imunológico , Ligantes , Camundongos , Molibdênio/uso terapêutico , Neoplasias de Mama Triplo Negativas/patologia , Microambiente Tumoral
7.
J Nanobiotechnology ; 20(1): 210, 2022 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-35524268

RESUMO

A sort of composite hydrogel with good biocompatibility, suppleness, high conductivity, and anti-inflammatory activity based on polyvinyl alcohol (PVA) and molybdenum sulfide/graphene oxide (MoS2/GO) nanomaterial has been developed for spinal cord injury (SCI) restoration. The developed (MoS2/GO/PVA) hydrogel exhibits excellent mechanical properties, outstanding electronic conductivity, and inflammation attenuation activity. It can promote neural stem cells into neurons differentiation as well as inhibit the astrocytes development in vitro. In addition, the composite hydrogel shows a high anti-inflammatory effect. After implantation of the composite hydrogel in mice, it could activate the endogenous regeneration of the spinal cord and inhibit the activation of glial cells in the injured area, thus resulting in the recovery of locomotor function. Overall, our work provides a new sort of hydrogels for SCI reparation, which shows great promise for improving the dilemma in SCI therapy.


Assuntos
Álcool de Polivinil , Traumatismos da Medula Espinal , Animais , Anti-Inflamatórios/uso terapêutico , Dissulfetos , Grafite , Hidrogéis , Camundongos , Molibdênio/uso terapêutico , Nanogéis , Traumatismos da Medula Espinal/tratamento farmacológico
8.
J Am Chem Soc ; 143(36): 14635-14645, 2021 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-34410692

RESUMO

Antibodies are recognition molecules that can bind to diverse targets ranging from pathogens to small analytes with high binding affinity and specificity, making them widely employed for sensing and therapy. However, antibodies have limitations of low stability, long production time, short shelf life, and high cost. Here, we report a facile approach for the design of luminescent artificial antibodies with nonbiological polymeric recognition phases for the sensitive detection, rapid identification, and effective inactivation of pathogenic bacteria. Transition-metal dichalcogenide (TMD) nanosheets with a neutral dextran phase at the interfaces selectively recognized S. aureus, whereas the nanosheets bearing a carboxymethylated dextran phase selectively recognized E. coli O157:H7 with high binding affinity. The bacterial binding sites recognized by the artificial antibodies were thoroughly identified by experiments and molecular dynamics simulations, revealing the significance of their multivalent interactions with the bacterial membrane components for selective recognition. The luminescent WS2 artificial antibodies could rapidly detect the bacteria at a single copy from human serum without any purification and amplification. Moreover, the MoSe2 artificial antibodies selectively killed the pathogenic bacteria in the wounds of infected mice under light irradiation, leading to effective wound healing. This work demonstrates the potential of TMD artificial antibodies as an alternative to antibodies for sensing and therapy.


Assuntos
Antibacterianos/uso terapêutico , Infecções por Escherichia coli/tratamento farmacológico , Substâncias Luminescentes/uso terapêutico , Nanoestruturas/uso terapêutico , Animais , Antibacterianos/química , Antibacterianos/efeitos da radiação , Dextranos/química , Escherichia coli O157/efeitos dos fármacos , Escherichia coli O157/isolamento & purificação , Luz , Substâncias Luminescentes/química , Substâncias Luminescentes/efeitos da radiação , Camundongos , Simulação de Dinâmica Molecular , Molibdênio/química , Molibdênio/efeitos da radiação , Molibdênio/uso terapêutico , Nanoestruturas/química , Nanoestruturas/efeitos da radiação , Terapia Fototérmica , Compostos de Selênio/química , Compostos de Selênio/efeitos da radiação , Compostos de Selênio/uso terapêutico , Pele/microbiologia , Análise Espectral Raman , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/isolamento & purificação , Sulfetos/química , Sulfetos/efeitos da radiação , Sulfetos/uso terapêutico , Compostos de Tungstênio/química , Compostos de Tungstênio/efeitos da radiação , Compostos de Tungstênio/uso terapêutico , Cicatrização/efeitos dos fármacos
9.
J Nanobiotechnology ; 19(1): 36, 2021 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-33536031

RESUMO

Owing to the hypoxia status of the tumor, the reactive oxygen species (ROS) production during photodynamic therapy (PDT) of the tumor is less efficient. Herein, a facile method which involves the synthesis of Mg-Mn-Al layered double hydroxides (LDH) clay with MoS2 doping in the surface and anionic layer space of LDH was presented, to integrate the photo-thermal effect of MoS2 and imaging and catalytic functions of Mg-Mn-Al LDH. The designed LDH-MoS2 (LMM) clay composite was further surface-coated with bovine serum albumin (BSA) to maintain the colloidal stability of LMM in physiological environment. A photosensitizer, chlorin e6 (Ce6), was absorbed at the surface and anionic layer space of LMM@BSA. In the LMM formulation, the magnetic resonance imaging of Mg-Mn-Al LDH was enhanced thanks to the reduced and acid microenvironment of the tumor. Notably, the ROS production and PDT efficiency of Ce6 were significantly improved, because LMM@BSA could catalyze the decomposing of the overexpressed H2O2 in tumors to produce oxygen. The biocompatible LMM@BSA that played the synergism with tumor microenvironment is a promising candidate for the effective treatment of cancer.


Assuntos
Catalase/uso terapêutico , Dissulfetos/uso terapêutico , Molibdênio/uso terapêutico , Nanoestruturas/uso terapêutico , Neoplasias/terapia , Fármacos Fotossensibilizantes/uso terapêutico , Porfirinas/uso terapêutico , Animais , Materiais Biomiméticos/síntese química , Materiais Biomiméticos/uso terapêutico , Clorofilídeos , Células HT29 , Humanos , Hidróxidos/uso terapêutico , Imageamento por Ressonância Magnética/métodos , Camundongos , Neoplasias/diagnóstico por imagem , Neoplasias/metabolismo , Fotoquimioterapia/métodos , Terapia Fototérmica/métodos , Espécies Reativas de Oxigênio/metabolismo , Nanomedicina Teranóstica/métodos
10.
Curr Opin Neurol ; 33(4): 534-542, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32657896

RESUMO

PURPOSE OF REVIEW: The aim of this article is to review recent developments in the areas of the disease features and treatment of Wilson disease, and survey disorders that share its pathophysiology or clinical symptoms. RECENT FINDINGS: Knowledge of the clinical spectrum of Wilson disease has expanded with recognition of patients who present in atypical age groups - patients with very early onset (<5 years) and those in whom symptoms present in mid-to-late adulthood. A disease phenotype with dominant psychiatric features and increased risk of cardiac problems and various sleep disorders have been identified.In addition to a better understanding of the phenotype of Wilson disease itself, features of some related disorders ('Wilson disease-mimics') have been described leading to a better understanding of copper homeostasis in humans. These disorders include diseases of copper disposition, such as mental retardation, enteropathy, deafness, neuropathy, ichthyosis, keratoderma syndrome, Niemann-Pick type C, and certain congenital disorders of glycosylation, as well as analogous disorders of iron and manganese metabolism.Outcomes for existing treatments, including in certain patient subpopulations of interest, are better known. Novel treatment strategies being studied include testing of bis-choline tetrathiomolybdate in phase 2 clinical trial as well as various preclinical explorations of new copper chelators and ways to restore ATP7B function or repair the causative gene. SUMMARY: Recent studies have expanded the phenotype of Wilson disease, identified rare inherited metal-related disorders that resemble Wilson disease, and studied long-term outcomes of existing treatments. These developments can be expected to have an immediate as well as a long-term impact on the clinical management of the disease, and point to promising avenues for future research.


Assuntos
ATPases Transportadoras de Cobre/genética , Cobre/metabolismo , Degeneração Hepatolenticular/diagnóstico , Molibdênio/uso terapêutico , Ensaios Clínicos como Assunto , ATPases Transportadoras de Cobre/metabolismo , Degeneração Hepatolenticular/tratamento farmacológico , Degeneração Hepatolenticular/genética , Degeneração Hepatolenticular/metabolismo , Humanos , Fenótipo
11.
Liver Int ; 39(11): 2136-2152, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31206982

RESUMO

BACKGROUND & AIMS: Wilson disease (WD) is a rare disorder of copper metabolism. The objective of this systematic review was to determine the comparative effectiveness and safety of common treatments of WD. METHODS: We included WD patients of any age or stage and the study drugs D-penicillamine, zinc salts, trientine and tetrathiomolybdate. The control could be placebo, no treatment or any other treatment. We included prospective, retrospective, randomized and non-randomized studies. We searched Medline and Embase via Ovid, the Cochrane Central Register of Controlled Trials, and screened reference lists of included articles. Where possible, we applied random-effects meta-analyses. RESULTS: The 23 included studies reported on 2055 patients and mostly compared D-penicillamine to no treatment, zinc, trientine or succimer. One study compared tetrathiomolybdate and trientine. Post-decoppering maintenance therapy was addressed in one study only. Eleven of 23 studies were of low quality. When compared to no treatment, D-penicillamine was associated with a lower mortality (odds ratio 0.013; 95% CI 0.0010 to 0.17). When compared to zinc, there was no association with mortality (odds ratio 0.73; 95% CI 0.16 to 3.40) and prevention or amelioration of clinical symptoms (odds ratio 0.84; 95% CI 0.48 to 1.48). Conversely, D-penicillamine may have a greater impact on side effects and treatment discontinuations than zinc. CONCLUSIONS: There are some indications that zinc is safer than D-penicillamine therapy while being similarly effective in preventing or reducing hepatic or neurological WD symptoms. Study quality was low warranting cautious interpretation of our findings.


Assuntos
Quelantes/efeitos adversos , Quelantes/uso terapêutico , Degeneração Hepatolenticular/tratamento farmacológico , Zinco/uso terapêutico , Cobre/metabolismo , Humanos , Fígado/metabolismo , Molibdênio/efeitos adversos , Molibdênio/uso terapêutico , Penicilamina/efeitos adversos , Penicilamina/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Trientina/efeitos adversos , Trientina/uso terapêutico , Zinco/efeitos adversos
12.
Xenobiotica ; 49(3): 332-338, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29460662

RESUMO

1. WTX101 (bis-choline tetrathiomolybdate) is an investigational copper (Cu)-protein-binding agent developed for the treatment of Wilson disease (WD), a rare genetic disorder caused by mutations in the ATP7B Cu-transporter and resulting in toxic Cu accumulation. 2. Mass balance of a single intravenous WTX101 dose, measured as molybdenum (Mo), was assessed over 168 h in control (Long Evans Agouti [LEA]) and Long-Evans Cinnamon (LEC) rats, a WD model. 3. In LEC rats, Mo was partially excreted (up to 45%); 29% by renal clearance, and faecal clearance, still ongoing at 168 h, accounted for 16%. In contrast, in LEA rats, Mo was almost fully excreted (∼87%); 79% was renally cleared with only 7% faecal excretion. 4. In LEC rats, the proportion of faecal to renal Mo excretion was enhanced (4:6) compared to controls (1:9). 5. Substantially more Mo was found in LEC liver and kidney compared with LEA tissues, in line with tissue Cu distribution. 6. These findings are consistent with the WTX101 mechanism of action: in the WD model, excess Cu is removed from hepatic metallothionein and retained within the stable tetrathiomolybdate-Cu-albumin tripartite complex, preventing tetrathiomolybdate degradation and resulting in less urinary elimination and greater faecal excretion than in controls.


Assuntos
Quelantes/farmacocinética , Cobre/metabolismo , Degeneração Hepatolenticular/tratamento farmacológico , Molibdênio/farmacocinética , Animais , Bile/química , Transporte Biológico/genética , Quelantes/metabolismo , Quelantes/uso terapêutico , Fezes/química , Molibdênio/metabolismo , Molibdênio/uso terapêutico , Ratos , Urina/química
13.
Nano Lett ; 18(9): 6037-6044, 2018 09 12.
Artigo em Inglês | MEDLINE | ID: mdl-30141945

RESUMO

Accurate imaging of glutathione (GSH) in vivo is able to provide real-time visualization of physiological and pathological conditions. Herein, we successfully synthesize bimetallic oxide MnMoOX nanorods as an intelligent nanoprobe for in vivo GSH detection via photoacoustic (PA) imaging. The obtained MnMoOX nanoprobe with no near-infrared (NIR) absorption in the absence of GSH would exhibit strong GSH-responsive NIR absorbance, endowing PA imaging detection of GSH. Due to the up-regulated GSH concentration in the tumor microenvironment, our MnMoOX nanoprobe could be utilized for in vivo tumor-specific PA imaging. Moreover, MnMoOX nanorods with GSH-responsive NIR absorbance could also be employed to achieve tumor-specific photothermal therapy (PTT). Importantly, such MnMoOX nanorods show inherent biodegradability and could be rapidly cleared out from the body, minimizing their long-term body retention and potential toxicity. Our work presents a new type of GSH-responsive nanoprobe based on bimetallic oxide nanostructures, promising for tumor-specific imaging and therapy.


Assuntos
Glutationa/análise , Compostos de Manganês/química , Molibdênio/química , Nanotubos/química , Neoplasias/diagnóstico , Óxidos/química , Técnicas Fotoacústicas/métodos , Nanomedicina Teranóstica/métodos , Animais , Hipertermia Induzida/métodos , Compostos de Manganês/uso terapêutico , Camundongos , Molibdênio/uso terapêutico , Nanotubos/ultraestrutura , Neoplasias/terapia , Óxidos/uso terapêutico , Fototerapia/métodos , Microambiente Tumoral
14.
Bioconjug Chem ; 29(2): 559-570, 2018 02 21.
Artigo em Inglês | MEDLINE | ID: mdl-29376319

RESUMO

Liver cancer is currently among the most challenging cancers to diagnose and treat. It is of prime importance to minimize the side effects on healthy tissues and reduce drug resistance for precise diagnoses and effective treatment of liver cancer. Herein, we report a facile but high-yield approach to fabricate a multifunctional nanomaterial through the loading of chitosan and metformin on Mn-doped Fe3O4@MoS2 nanoflowers. Mn-doped Fe3O4 cores are used as simultaneous T1/T2 magnetic resonance imaging (MRI) agents for sensitive and accurate cancer diagnosis, while MoS2 nanosheets are used as effective near-infrared photothermal conversion agents for potential photothermal therapy. The surface-functionalized chitosan was able not only to improve the dispersibility of Mn-doped Fe3O4@MoS2 nanoflowers in biofluids and increase their biocompatibility, but also to significantly enhance the photothermal effect. Furthermore, metformin loading led to high suppression and eradication of hepatoma cells when photothermally sensitized, but exhibited negligible effects on normal liver cells. Due to its excellent combination of T1/T2 MRI properties with sensitive chemotherapeutic and photothermal effects, our study highlights the promise of developing multifunctional nanomaterials for accurate multimodal imaging-guided, and highly sensitive therapy of liver cancer.


Assuntos
Dissulfetos/química , Óxido Ferroso-Férrico/química , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/terapia , Manganês/química , Molibdênio/química , Nanoestruturas/química , Linhagem Celular Tumoral , Quitosana/química , Quitosana/uso terapêutico , Dissulfetos/uso terapêutico , Óxido Ferroso-Férrico/uso terapêutico , Humanos , Hipertermia Induzida/métodos , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/uso terapêutico , Imageamento por Ressonância Magnética/métodos , Manganês/uso terapêutico , Metformina/administração & dosagem , Metformina/uso terapêutico , Molibdênio/uso terapêutico , Imagem Multimodal/métodos , Nanoestruturas/uso terapêutico , Fototerapia/métodos
15.
Photochem Photobiol Sci ; 17(10): 1337-1345, 2018 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-30141822

RESUMO

Photothermal therapy (PTT) is providing new opportunities for killing cancer cells. In this work, we introduce a new nanomedicine based on spherical MoS2 nanoparticles for PTT treatment of tumors, prepared using "green" bottom-up technology. To increase water solubility and avoid rapid clearance by the reticuloendothelial system, polyethylene glycol (PEG) was used to coat them. These MoS2-PEG nanospheres with an appropriate size (∼100 nm) exhibit high photothermal conversion efficiency (26.7%). In vitro cellular studies revealed that the MoS2-PEG nanospheres showed negligible cytotoxicity. Additionally, through combining the MoS2-PEG nanosphere samples with NIR irradiation at 808 nm, excellent in vitro tumor cell killing efficacy was achieved. In the 4T1 tumor model, the MoS2-PEG nanospheres exhibited good antitumor efficiency in vivo, displaying complete tumor inhibition over 16 days after treatment. Therefore, MoS2-PEG nanospheres played an important role in tumor destruction, and this concept for developing spherical MoS2-based nanomedicines can serve as a platform technology for the next generation of in vivo PTT agents.


Assuntos
Neoplasias da Mama/terapia , Dissulfetos/uso terapêutico , Molibdênio/uso terapêutico , Nanosferas/uso terapêutico , Nanotecnologia/métodos , Fototerapia/métodos , Animais , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Dissulfetos/química , Feminino , Hipertermia Induzida/métodos , Camundongos , Molibdênio/química , Nanomedicina/métodos , Nanosferas/química , Nanosferas/ultraestrutura , Polietilenoglicóis/química , Polietilenoglicóis/uso terapêutico
16.
Internist (Berl) ; 58(12): 1233-1241, 2017 Dec.
Artigo em Alemão | MEDLINE | ID: mdl-29098318

RESUMO

Wilson's disease (WD) is a rare autosomal recessive disorder characterized by abnormal copper accumulation. Presenting a broad variety of phenotypes and, thus, being a chameleon within the group of metabolic diseases, the manifold clinical symptoms of WD can include hepatologic, neurologic, and psychiatric manifestations. Early onset presentations in infancy and late-onset manifestations in adults older than 70 years of age have been described. If the typical laboratory blood test values are missing, the diagnosis of WD may be difficult and often involves a combination of different parameters. Novel test methods like the identification of the relative exchangeable copper have not been validated within a sufficient cohort of WD patients as of yet and therefore do not currently play a crucial role within the clinical setting. Consequently any patient with reasonable suspected diagnosis of WD needs to be presented to a (pediatric) gastroenterologist and/or (pediatric) neurologist. Different medical treatments including drugs such as copper chelating agents are commonly used in the clinical setting. Liver transplantation may be the ultima ratio in selected patients. Dietary changes involving a low copper diet play only a minor role. Due to the fact the use of tetrathiomolybdate is still not approved, the treatment of advanced and progressive neurologic symptoms remains a major challenge. In any case, life-long medical supervision and treatment governed by a specialist is absolutely essential. Early diagnosis and early and life-long treatment lead to better prognoses and do not negatively influence the overall life expectancy.


Assuntos
Degeneração Hepatolenticular/diagnóstico , Degeneração Hepatolenticular/terapia , Quelantes/uso terapêutico , Aberrações Cromossômicas , Cobre/administração & dosagem , Cobre/sangue , Dietoterapia , Genes Recessivos/genética , Degeneração Hepatolenticular/sangue , Degeneração Hepatolenticular/genética , Humanos , Transplante de Fígado , Molibdênio/uso terapêutico , Penicilamina/uso terapêutico , Fenótipo , Zinco/uso terapêutico
17.
Int J Vitam Nutr Res ; 85(1-2): 88-103, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26780281

RESUMO

UNLABELLED: Diabetes mellitus is a chronic physiological glucose metabolic disorder. Its high prevalence globally has a significant impact on the quality of life. The management of diabetes includes non-pharmacological and glucose lowering agents. Although these methods are effective, they have drawbacks. This has led to a search for alternative therapy in macro and micro-minerals from dietary foods and plants. There is therefore a need to review, identify and classify their modes of action in diabetes mellitus therapy. MATERIALS AND METHODS: This review was carried out using comprehensive literature reports on the use of mineral elements in the management of diabetes. Empirical online searches were conducted for different elements that have been studied for their anti-diabetic potentials both in vivo and in vitro. The University of Fort Hare's online database was also used. RESULTS AND DISCUSSION: The results indicate that magnesium, molybdenum, zinc, vanadium and manganese facilitate glucose catabolism. Chromium, vanadium, zinc, molybdenum and magnesium can enhance insulin activity while molybdenum, manganese and zinc stimulate lipogenesis. Zinc and iron can modulate glucose, metabolizing enzymes in the gastrointestinal tract and limit oxidative stress, respectively. These agents have similar mechanisms to conventional drugs in ameliorating diabetic status and other associated complications. CONCLUSION: The mechanisms of these elements are well known, however, the synergetic effects of their combinations are still obscure. Literature on their safe dose(s) is still scanty. Evaluation of other useful macro and micro-minerals should also be undertaken. It is envisaged that the use of mineral supplements will promote good health in diabetics.


Assuntos
Complicações do Diabetes/tratamento farmacológico , Diabetes Mellitus/tratamento farmacológico , Minerais/uso terapêutico , Cromo/uso terapêutico , Sinergismo Farmacológico , Glucose/metabolismo , Humanos , Ferro/uso terapêutico , Magnésio/uso terapêutico , Manganês/uso terapêutico , Minerais/administração & dosagem , Molibdênio/uso terapêutico , Estresse Oxidativo/efeitos dos fármacos , Vanádio/uso terapêutico , Zinco/uso terapêutico
18.
ScientificWorldJournal ; 2014: 291925, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25580456

RESUMO

Metal-on-metal hip resurfacing (MOM-HR) is offered as an alternative to traditional hip arthroplasty for young, active adults with advanced osteoarthritis. Nevertheless, concerns remain regarding wear and corrosion of the bearing surfaces and the resulting increase in metal ion levels. We evaluated three cohorts of patients with Birmingham hip resurfacing (BHR) at an average follow-up of 2, 5, and 9 years. We asked whether there would be differences in ion levels between the cohorts and inside the gender. Nineteen patients were prospectively analyzed. The correlation with clinical-radiographic data was also performed. Chromium, cobalt, nickel, and molybdenum concentrations were measured by atomic absorption spectrophotometry. Chromium and cobalt levels demonstrated a tendency to decrease over time. Such tendency was present only in females. An inverse correlation between chromium, implant size, and Harris hip score was present at short term; it disappeared over time together with the decreased ion levels. The prospective analysis showed that, although metal ion levels remained fairly constant within each patient, there was a relatively large variation between subjects, so mean data in this scenario must be interpreted with caution. The chronic high exposure should be carefully considered during implant selection, particularly in young subjects, and a stricter monitoring is mandatory.


Assuntos
Artroplastia de Quadril , Prótese de Quadril , Desenho de Prótese , Adulto , Idoso , Cromo/efeitos adversos , Cromo/uso terapêutico , Cobalto/efeitos adversos , Cobalto/uso terapêutico , Estudos de Coortes , Corrosão , Feminino , Articulação do Quadril/fisiopatologia , Articulação do Quadril/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Molibdênio/química , Molibdênio/uso terapêutico , Níquel/química , Níquel/uso terapêutico
19.
Biomater Adv ; 156: 213701, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38039808

RESUMO

Pathological bacterial infection poses a serious threat to public health security. The excessive use of antibiotics has resulted in a serious decline in treatment effect and bacterial resistance. For the treatment of infected wounds, we compounded dopamine-assisted exfoliated molybdenum disulfide (MoS2@PDA) into lipoic acid modified chitosan (LAMC) to obtain a composite hydrogel dressing (LAMC-MoS2@PDA). LAMC-MoS2@PDA hydrogels exhibited excellent photothermal conversion ability and the LAMC-MoS2@PDA2 group (0.3 wt%) has a photothermal conversion efficiency of 26.29 %. Meanwhile, they showed good biocompatibility and ROS scavenging activity in vitro. Photothermal therapy usually utilizes photothermal agents to convert near-infrared light into heat energy for bacterial cell membrane destruction and bacterial protein inactivation. Under the near-infrared light irradiation, the antibacterial ratio of LAMC-MoS2@PDA hydrogels against Staphylococcus aureus and Escherichia coli reached nearly 100 %, and the morphology of the bacteria showed obvious contraction and cleavage. The hydrogels also showed an excellent antibacterial effect and wound healing promotion in the infected wound of rats. In particular, the LAMC-MoS2@PDA2 (+) group (with NIR) showed almost complete wound closure after 14 days, indicating that the LAMC-MoS2@PDA hydrogels have great potential in clinical anti-infected treatment.


Assuntos
Quitosana , Hidrogéis , Animais , Ratos , Hidrogéis/farmacologia , Molibdênio/farmacologia , Molibdênio/uso terapêutico , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Proteínas de Bactérias , Escherichia coli
20.
J Trace Elem Med Biol ; 82: 127368, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38150949

RESUMO

BACKGROUND: Hair loss is a common dermatological condition including various types such as alopecia areata, androgenetic alopecia, etc. Minoxidil is a topical medication used for treating hair loss, which is effective for various types of alopecia. However, minoxidil has limitations in treating hair loss, such as slow onset of action and low efficacy, and it cannot effectively inhibit one of the major pathogenic factors of hair loss - excessive oxidative stress. METHODS: Transition metal elements with rapid electron transfer, such as molybdenum, have been extensively studied and applied for inhibiting oxidative stress. We established a mouse model for hair growth and intervened with nano-sized molybdenum, minoxidil, and a combination of both. The physicochemical properties of nano-sized molybdenum enabled it to mediate oxidative stress more quickly. RESULTS: The results showed that nano-sized molybdenum can accelerate hair growth, increase the number of local hair follicles, and reduce the expression of oxidative stress-related molecules such as iNOS, COX2, and androgen receptors. The combination of nano-sized molybdenum and minoxidil showed an additive effect in promoting hair growth. CONCLUSION: Our findings suggest that nano-sized molybdenum might be a potential topical medication for treating hair loss by inhibiting the oxidative stress pathway. Nano-sized molybdenum, alone or in combination with minoxidil, could be a promising therapeutic approach for patients with hair loss, particularly those who do not respond well to current treatments. Further clinical studies are warranted to confirm the efficacy and safety of this novel treatment.


Assuntos
Alopecia em Áreas , Minoxidil , Animais , Camundongos , Humanos , Minoxidil/farmacologia , Minoxidil/uso terapêutico , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Molibdênio/farmacologia , Molibdênio/uso terapêutico , Método Duplo-Cego , Alopecia/tratamento farmacológico , Resultado do Tratamento
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA