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1.
Int J Mol Sci ; 24(22)2023 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-38003398

RESUMO

Dysregulated metal homeostasis is associated with many pathological conditions, including arthritic diseases. Osteoarthritis and rheumatoid arthritis are the two most prevalent disorders that damage the joints and lead to cartilage and bone destruction. Recent studies show that the levels of zinc (Zn) and copper (Cu) are generally altered in the serum of arthritis patients. Therefore, metal dyshomeostasis may reflect the contribution of these trace elements to the disease's pathogenesis and manifestations, suggesting their potential for prognosis and treatment. Carnosine (Car) also emerged as a biomarker in arthritis and exerts protective and osteogenic effects in arthritic joints. Notably, its zinc(II) complex, polaprezinc, has been recently proposed as a drug-repurposing candidate for bone fracture healing. On these bases, this review article aims to provide an overview of the beneficial roles of Cu and Zn in bone and cartilage health and their potential application in tissue engineering. The effects of Car and polaprezinc in promoting cartilage and bone regeneration are also discussed. We hypothesize that polaprezinc could exchange Zn for Cu, present in the culture media, due to its higher sequestering ability towards Cu. However, future studies should unveil the potential contribution of Cu in the beneficial effects of polaprezinc.


Assuntos
Artrite , Carnosina , Compostos Organometálicos , Humanos , Zinco/farmacologia , Carnosina/farmacologia , Cobre/farmacologia , Compostos Organometálicos/farmacologia , Compostos de Zinco/farmacologia , Proteínas de Ciclo Celular/farmacologia , Cartilagem
2.
Georgian Med News ; (335): 54-59, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37042589

RESUMO

The purpose of this study was to analyze the effects of cadmium toxicity on rat embryogenesis when exposed to other heavy metal citrates. Despite the variety of scientific publications discussing the influence of cadmium on mammalian postnatal development, the effect of this metal on embryogenesis has not yet been sufficiently studied. In this experimental study, cadmium chloride was administered to experimental pregnant female Wistar rats at a daily dose of 1.0 mg/kg. Rats were allocated at random into groups receiving either cadmium chloride alone or additional zinc citrate, cerium citrate, or nanocomposite (based on iodine, sulfur, and selenium citrate). The control group received distilled water at an equivalent volume. In each group, operational intervention occurred at the 13th and 20th day of gestation to assess numbers of live fetuses, corpora lutea, pre-implantation losses, post-implantation losses, and total implantation losses. When cadmium chloride alone was administered, a pronounced embryotoxic effect was observed, manifested as a significant decrease in the number of live fetuses. Experimental groups which received cadmium chloride with zinc citrate, cerium citrate, or nanocomposite had an increased number of live fetuses and corpora lutea, as well as a decreased number of implantation losses, compared to the group which only received cadmium chloride. Each combination of cerium, zinc, and selenium nanocomposite citrates demonstrated a compensatory effect on all measures of embryogenesis impacted by cadmium embryotoxicity. Thus, administration of the citrates of cerium, zinc, and selenium nanocomposite reduces cadmium embryotoxicity and its accumulation in the body.


Assuntos
Cloreto de Cádmio , Citratos , Desenvolvimento Embrionário , Metais Pesados , Animais , Feminino , Gravidez , Ratos , Cloreto de Cádmio/toxicidade , Citratos/farmacologia , Implantação do Embrião/efeitos dos fármacos , Mamíferos , Ratos Wistar , Doença Crônica , Desenvolvimento Embrionário/efeitos dos fármacos , Metais Pesados/farmacologia , Metais Pesados/toxicidade , Cério/farmacologia , Nanocompostos , Compostos de Zinco/farmacologia , Compostos de Selênio/farmacologia , Compostos de Iodo/farmacologia , Compostos de Enxofre/farmacologia
3.
Oral Dis ; 29(8): 3243-3258, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35877467

RESUMO

OBJECTIVES: Zinc sulfide nanoparticles (ZnS NPs), as one of the quantum dots less than 10 nm, possess unique size-dependent autofluorescence. Excitation of their valence electrons by energy higher than the bandgap reveals the ZnS NPs' inherited photocatalysis with additive cytotoxic consequences of reactive oxygen species (ROS) release. Coupling the cytotoxicity of photoactivated ZnS NPs with their autofluorescence would be a novel theranostic modality, combating superficially accessible carcinoma. MATERIAL AND METHODS: After synthesizing and characterization of ZnS NPs, we verified their photocatalysis and electron donation upon UV excitation in degrading organic dye and DNA cleavage, respectively. We then tested the efficacy of UV-activated ZnS NPs to induce ROS-dependent apoptosis in squamous cell carcinoma and breast cancer cell lines. RESULTS: The energetic electron-hole pairs generated upon UV excitation of ZnS NPs with the consequent cascade of ROS release revealed potent apoptotic cancer cell deaths, compared with single treatment modalities of nonexcited nanoparticles and UV. Moreover, the inherited luminescence of ZnS NPs enabled visualization of their predominant intracytoplasmic uptake with tracking of their cellular response. CONCLUSION: The intensified luminescence and the fortified cytotoxicity of photoactivated ZnS NPs enhance their theranostic qualifications, boosting their antitumorigenic use.


Assuntos
Nanopartículas , Neoplasias , Humanos , Espécies Reativas de Oxigênio/metabolismo , Medicina de Precisão , Compostos de Zinco/farmacologia , Sulfetos/farmacologia
4.
Sci Rep ; 12(1): 1943, 2022 02 04.
Artigo em Inglês | MEDLINE | ID: mdl-35121767

RESUMO

T helper (Th) cells provide immunity to pathogens but also contribute to detrimental immune responses during allergy and autoimmunity. Th2 cells mediate asthmatic airway inflammation and Th1 cells are involved in the pathogenesis of multiple sclerosis. T cell activation involves complex transcriptional networks and metabolic reprogramming, which enable proliferation and differentiation into Th1 and Th2 cells. The essential trace element zinc has reported immunomodulatory capacity and high zinc concentrations interfere with T cell function. However, how high doses of zinc affect T cell gene networks and metabolism remained so far elusive. Herein, we demonstrate by means of transcriptomic analysis that zinc aspartate (UNIZINK), a registered pharmaceutical infusion solution with high bioavailability, negatively regulates gene networks controlling DNA replication and the energy metabolism of murine CD3/CD28-activated CD4+ T cells. Specifically, in the presence of zinc, CD4+ T cells show impaired expression of cell cycle, glycolytic and tricarboxylic acid cycle genes, which functionally cumulates in reduced glycolysis, oxidative phosphorylation, metabolic fitness and viability. Moreover, high zinc concentrations impaired nuclear expression of the metabolic transcription factor MYC, prevented Th1 and Th2 differentiation in vitro and reduced Th1 autoimmune central nervous system (CNS) inflammation and Th2 asthmatic airway inflammation induced by house dust mites in vivo. Together, we find that higher zinc doses impair the metabolic fitness of CD4+ T cells and prevent Th1 CNS autoimmunity and Th2 allergy.


Assuntos
Ácido Aspártico/análogos & derivados , Asma/tratamento farmacológico , Sistema Nervoso Central/efeitos dos fármacos , Encefalomielite Autoimune Experimental/tratamento farmacológico , Metabolismo Energético/efeitos dos fármacos , Agentes de Imunomodulação/farmacologia , Pulmão/efeitos dos fármacos , Ativação Linfocitária/efeitos dos fármacos , Pneumonia/tratamento farmacológico , Células Th1/efeitos dos fármacos , Células Th2/efeitos dos fármacos , Compostos de Zinco/farmacologia , Animais , Ácido Aspártico/farmacologia , Asma/genética , Asma/imunologia , Asma/metabolismo , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Sistema Nervoso Central/imunologia , Sistema Nervoso Central/metabolismo , Encefalomielite Autoimune Experimental/genética , Encefalomielite Autoimune Experimental/imunologia , Encefalomielite Autoimune Experimental/metabolismo , Metabolismo Energético/genética , Regulação da Expressão Gênica , Pulmão/imunologia , Pulmão/metabolismo , Ativação Linfocitária/genética , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Pneumonia/genética , Pneumonia/imunologia , Pneumonia/metabolismo , Pyroglyphidae/imunologia , Transdução de Sinais , Células Th1/imunologia , Células Th1/metabolismo , Células Th2/imunologia , Células Th2/metabolismo , Transcrição Gênica
5.
Mol Pharm ; 19(1): 115-123, 2022 01 03.
Artigo em Inglês | MEDLINE | ID: mdl-34927440

RESUMO

Herein, four zinc phthalocyanines (ZnPcs) with chiral lysine modification were synthesized. We found that the chirality of lysine and the chiral structure position strongly influence the properties of ZnPcs. Among the four ZnPcs, d-lysine-modified ZnPc through -NH2 on Cε [denoted N(ε)-d-lys-ZnPc] showed superior properties, including tumor enrichment, cancer cell uptake, and tumor retention capability, compared to the other three ZnPcs. Thus, chiral molecule modification is a simple and effective strategy to regulate the abovementioned properties to achieve a satisfactory antitumor outcome of drugs.


Assuntos
Aminoácidos/química , Isoindóis/farmacologia , Fármacos Fotossensibilizantes/farmacologia , Estereoisomerismo , Animais , Antineoplásicos/química , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Células HeLa/efeitos dos fármacos , Humanos , Isoindóis/síntese química , Isoindóis/química , Lisina/química , Camundongos , Transplante de Neoplasias , Compostos Organometálicos/síntese química , Compostos Organometálicos/química , Compostos Organometálicos/farmacologia , Fármacos Fotossensibilizantes/química , Compostos de Zinco/síntese química , Compostos de Zinco/química , Compostos de Zinco/farmacologia
6.
J Nutr Biochem ; 100: 108901, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34748925

RESUMO

A nutrition deficiency is one of the various causes of hearing loss. Zinc is an essential element for cell proliferation, antioxidant reactions, and the maintenance of hearing ability. Our previous studies have reported that the auditory brainstem response (ABR) threshold is increased in mice fed with zinc-deficient diets. However, the molecular mechanism of zinc involved in auditory system remains to be elucidated. In the present study, we examined the detrimental effects of zinc deficiency on cell cycle progression in murine auditory cells (HEI-OC1). The treatment of HEI-OC1 cells with 0.5 µM TPEN (N,N,N',N'-Tetrakis (2-pyridylmethyl) ethylenediamine) for 24 h inhibited cell proliferation, accumulation of reactive oxygen species (ROS), and induction of apoptosis. The cell proliferation block was caused by a G1/S phase arrest. Supplementation of the cell growth medium with 5 µM ZnCl2 after exposure to TPEN attenuated ROS accumulation and the arrest caused by the zinc deficiency. The ABR threshold was elevated in mice fed with a zinc-deficient diet. Additionally, we observed an increased expression of p21 and decreased expression of cyclin E and pRb in the spiral ganglion (SG), the organ of Corti (OC), Limbus (L), and stria vascularis (SV) in the zinc-deficient mouse cochlea. These results indicated that zinc is an essential nutrient for proliferation via the cell cycle and that a dysregulation of the cell cycle may cause hearing loss.


Assuntos
Ciclo Celular , Células Ciliadas Auditivas/citologia , Células Ciliadas Auditivas/metabolismo , Zinco/deficiência , Zinco/fisiologia , Animais , Apoptose , Pontos de Checagem do Ciclo Celular , Linhagem Celular , Proliferação de Células , Sobrevivência Celular , Cloretos/farmacologia , Cóclea/metabolismo , Etilenodiaminas/farmacologia , Potenciais Evocados Auditivos do Tronco Encefálico , Audição , Homeostase , Masculino , Camundongos , Camundongos Endogâmicos CBA , Oxirredução , Espécies Reativas de Oxigênio , Compostos de Zinco/farmacologia
7.
PLoS One ; 16(12): e0260662, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34941898

RESUMO

Human population is exceeding beyond the carrying capacity of earth resources and stresses like water shortage faced by the plants is jeopardizing the food security. Current research study was aimed to investigate the potentials of Zn-Aspartate (Zn-Asp), Zn-Sulphate (ZnSO4) and L-Aspartate (L-Asp) to be used as osmolytes and role of various levels of these chemicals in combating drought stress in maize plants in Punjab, Pakistan. Study was performed on two plots corresponding to drought and controlled environments. The lamina of maize plants was sprinkled row wise with various treatments including No spray (NS), water sprinkle (WS), sprinkle with ZnSO4 0.25% and 0.50%, sprinkle with Zn-Asp 0.25% and 0.50% and Foliar sprinkle of L-Asp 0.5% and 1%, respectively. Role of major osmoprotectants and secondary metabolites was analyzed and positive changes were found in total soluble sugars (41.16), flavonoids (5387.74), tocopherol content (9089.18), ascorbic acid (645.27) and anthocyanin (14.84) conc. which assists in mitigating drought menace on maize. Shoot mineral ions (Ca, K, Zn, P, Mg and N) status of water stressed maize plants was also analyzed and it was found that application experimental dose enhanced their availability to crop. Physio-biochemical studies were performed on antioxidants enzymes like superoxide dismutase (SOD), peroxidase (POD), carotenoid content (CC), malondialdehyde, hydrogen peroxide, aspartate and free amino acid contents. The activity of SOD was increased by 28.5% and activity of POD was increased by 33.33% due to foliar applied 0.5% Zn-Asp under drought stress. Photosynthetic pigments (chlorophyll A, B and total chlorophyll content) analysis was also carried out in this study. It was found that conc. of different chlorophylls pigments increased (chl-A: 2.24, chl-B: 25.12, total chl: 24.30) which enhanced photosynthetic activity culminating into better growth and yield). The level of malondialdehyde and hydrogen peroxide decreased by 43.9% and 32.8% respectively on treatment with 0.5% Zn-Asp proving the efficacy of the treatment in drought amelioration. Study reveals that Zn-Asp induced modulations are far better than conventional sulphate salts in mitigating water scarce environment. Current study recommends the use of the Zn-Asp to meet the global food and agricultural challenges as compared to ZnSO4 and L-Asp due to its better drought amelioration properties. This research provides valuable informations which can used for future research and practical use in agriculture fields by indigenous and other people to enhance yield of maize to meet the food necessities of country.


Assuntos
Ácido Aspártico/análogos & derivados , Ácido Aspártico/farmacologia , Secas , Zea mays/efeitos dos fármacos , Zea mays/crescimento & desenvolvimento , Compostos de Zinco/farmacologia , Sulfato de Zinco/farmacologia , Antioxidantes/farmacologia , Carboidratos , Caseínas/metabolismo , Peroxidação de Lipídeos , Lipídeos , Fotossíntese , Proteínas de Vegetais Comestíveis/metabolismo , Zea mays/metabolismo
8.
J Mater Sci Mater Med ; 32(12): 149, 2021 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-34862920

RESUMO

As a potential biodegradable implant material, zinc (Zn) alloys have attracted increasing attention due to their good biocompatibility and moderate degradation rate. Zn and its alloys are expected to become candidate materials for medical devices. The metals implanted in the human body will inevitably undergo friction in the human body before it is completely degraded. Friction and wear are essential factors which may cause medical devices' service failure. However, there are still few studies on the friction and wear properties of biodegradable Zn-based alloys in the human body, and most studies just focus on the mechanical properties, degradation properties and biocompatibility of the alloys. Thus, it is crucial to study the friction and wear properties of Zn and its alloys. In the present work, we investigated the tribological properties of biodegradable pure Zn and Zn-X (Li, Cu, Ge) alloys. Our study found that under simulated body fluid and dry friction conditions, the addition of alloying elements Li and Cu can improve the friction properties of Zn. Among the four metals, Zn-0.5Li alloy has the lowest friction coefficient and the best wear resistance. Hank's solution has lubricating and corrosive effects. That is to say, when the alloy is rubbed in Hank's solution, it can not only be protected by the lubrication of the solution, but also tribocorrosion will occur as well.


Assuntos
Cobre/química , Germânio/química , Lítio/química , Compostos de Zinco/farmacologia , Zinco/farmacologia , Implantes Absorvíveis , Ligas/química , Ligas/farmacologia , Humanos , Teste de Materiais , Zinco/química , Compostos de Zinco/química
9.
Anticancer Res ; 41(11): 5453-5459, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34732414

RESUMO

BACKGROUND: Zinc is a mineral that is essential for biological molecules, such as transcription factors, and is involved in the maintenance of intestinal homeostasis. Vitamin D signaling is mediated by vitamin D receptor (VDR) activated by 1α,25-dihydroxyvitamin D3 [1,25(OH)2D3] and is also important in intestinal functions, such as calcium absorption and epithelial barrier maintenance. However, the crosstalk between vitamin D signaling and zinc signaling in intestinal cells remains poorly understood. MATERIALS AND METHODS: Colon cancer SW480 and HCT116 cells were treated with zinc chloride (ZnCl2) with/without 1,25(OH)2D3 Expression of zinc-inducible genes [metallothionein 1A (MT1A) and MT2A] and VDR target genes [cytochrome P450 family 24 subfamily A member 1 (CYP24A1), transient receptor potential cation channel subfamily V member 6 (TRPV6) and cadherin 1 (CDH1)] was examined. RESULTS: Treatment of cells with ZnCl2 effectively induced MT1A and MT2A mRNA expression, and interestingly suppressed mRNA expression of CDH1, which was induced by 1,25(OH)2D3 in both cell lines. ZnCl2 also reduced the CDH1 protein level in HCT116 cells. CONCLUSION: Zinc signaling suppresses VDR-induced expression of CDH1.


Assuntos
Antígenos CD/metabolismo , Caderinas/metabolismo , Calcitriol/farmacologia , Cloretos/farmacologia , Neoplasias do Colo/metabolismo , Receptores de Calcitriol/agonistas , Compostos de Zinco/farmacologia , Antígenos CD/genética , Caderinas/genética , Neoplasias do Colo/genética , Neoplasias do Colo/patologia , Regulação Neoplásica da Expressão Gênica , Células HCT116 , Humanos , Metalotioneína/genética , Metalotioneína/metabolismo , Receptores de Calcitriol/metabolismo , Transdução de Sinais
10.
Eur J Histochem ; 65(s1)2021 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-34755507

RESUMO

Oxaliplatin is a third-generation chemotherapy drug mainly used for colorectal cancer treatment. However, it is also known to trigger neuropathy whose underlying neurobiological mechanisms are still under investigation and currently available treatments show limited efficacy. It is now established that neurons are not the only cell type involved in chronic pain and that glial cells, mainly astrocytes and microglia, are involved in the initiation and maintenance of neuropathy. Among all the pathogenetic factors involved in neuropathic pain, an oxaliplatin-dependent oxidative stress plays a predominant role. In our study, the antioxidant properties of magnesium (Mg), manganese (Mn) and zinc (Zn) salts were evaluated in order to counteract microglial activation induced by oxaliplatin. The antioxidant efficacy of these metals was evaluated by the means of molecular and morphological assays on the BV-2 microglial cell line. Our data clearly show that Mg, Mn and Zn are able to prevent oxaliplatin-dependent microglial alterations by reducing both oxidative and endoplasmic reticulum stress.


Assuntos
Antioxidantes/farmacologia , Cloretos/farmacologia , Cloreto de Magnésio/farmacologia , Compostos de Manganês/farmacologia , Oxaliplatina/toxicidade , Compostos de Zinco/farmacologia , Animais , Antígeno B7-2/metabolismo , Proteínas de Ligação ao Cálcio/metabolismo , Linhagem Celular , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Camundongos , Proteínas dos Microfilamentos/metabolismo , Microglia/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo
11.
Molecules ; 26(22)2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34833970

RESUMO

Photodynamic therapy (PDT) is a light-based cancer therapy approach that has shown promising results in treating various malignancies. Growing evidence indicates that cancer stem cells (CSCs) are implicated in tumor recurrence, metastasis, and cancer therapy resistance in colorectal cancer (CRC); thus, targeting these cells can ameliorate the prognosis of affected patients. Based on our bioinformatics results, SOX2 overexpression is significantly associated with inferior disease-specific survival and worsened the progression-free interval of CRC patients. Our results demonstrate that zinc phthalocyanine (ZnPc)-PDT with 12 J/cm2 or 24 J/cm2 irradiation can substantially decrease tumor migration via downregulating MMP9 and ROCK1 and inhibit the clonogenicity of SW480 cells via downregulating CD44 and SOX2. Despite inhibiting clonogenicity, ZnPc-PDT with 12 J/cm2 irradiation fails to downregulate CD44 expression in SW480 cells. Our results indicate that ZnPc-PDT with 12 J/cm2 or 24 J/cm2 irradiation can substantially reduce the cell viability of SW480 cells and stimulate autophagy in the tumoral cells. Moreover, our results show that ZnPc-PDT with 12 J/cm2 or 24 J/cm2 irradiation can substantially arrest the cell cycle at the sub-G1 level, stimulate the intrinsic apoptosis pathway via upregulating caspase-3 and caspase-9 and downregulating Bcl-2. Indeed, our bioinformatics results show considerable interactions between the studied CSC-related genes with the studied migration- and apoptosis-related genes. Collectively, the current study highlights the potential role of ZnPc-PDT in inhibiting stemness and CRC development, which can ameliorate the prognosis of CRC patients.


Assuntos
Neoplasias Colorretais/tratamento farmacológico , Isoindóis/farmacologia , Células-Tronco Neoplásicas/efeitos dos fármacos , Compostos Organometálicos/farmacologia , Fármacos Fotossensibilizantes/farmacologia , Compostos de Zinco/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Neoplasias Colorretais/patologia , Humanos , Células-Tronco Neoplásicas/patologia , Fotoquimioterapia
12.
Adv Mater ; 33(49): e2104037, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34622500

RESUMO

Although immunotherapy such as immune checkpoint inhibitors has shown promising efficacy in cancer treatment, the responsiveness among patients is relatively limited. Activation of the cyclic guanosine monophosphate-adenosine monophosphate synthase/interferon gene stimulator (cGAS/STING) signaling pathway to upregulate innate immunity has become an emerging strategy for enhancing tumor immunotherapy. Herein, ZnS@BSA (bovine serum albumin) nanoclusters synthesized via a self-assembly approach are reported, where the released zinc ions under acidic tumor microenvironment significantly enhance cGAS/STING signals. Meanwhile, intracellular zinc ions can produce reactive oxygen species, which is further facilitated by the generated H2 S gas from ZnS@BSA via specifically inhibiting catalase in hepatocellular carcinoma cells. It is found that the nanoclusters activate the cGAS/STING signals in mice, which promotes the infiltration of CD8+ T cells at the tumor site and cross-presentation of dendritic cells, leading to an improved immunotherapy efficacy against hepatocellular carcinoma.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Compostos de Zinco , Animais , Linfócitos T CD8-Positivos , Carcinoma Hepatocelular/terapia , Humanos , Imunoterapia , Neoplasias Hepáticas/terapia , Proteínas de Membrana/metabolismo , Nanopartículas Metálicas , Camundongos , Nucleotidiltransferases/genética , Nucleotidiltransferases/metabolismo , Sulfetos , Microambiente Tumoral , Compostos de Zinco/farmacologia
13.
Int J Mol Sci ; 22(19)2021 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-34638673

RESUMO

Steroid-associated osteonecrosis (SAON) is a chronic disease that leads to the destruction and collapse of bone near the joint that is subjected to weight bearing, ultimately resulting in a loss of hip and knee function. Zn2+ ions, as an essential trace element, have functional roles in improving the immunophysiological cellular environment, accelerating bone regeneration, and inhibiting biofilm formation. In this study, we reconstruct SAON lesions with a three-dimensional (3D)-a printed composite made of poly (epsilon-caprolactone) (PCL) and nanoparticulate Willemite (npW). Rabbit bone marrow stem cells were used to evaluate the cytocompatibility and osteogenic differentiation capability of the PCL/npW composite scaffolds. The 2-month bone regeneration was assessed by a Micro-computed tomography (micro-CT) scan and the expression of bone regeneration proteins by Western blot. Compared with the neat PCL group, PCL/npW scaffolds exhibited significantly increased cytocompatibility and osteogenic activity. This finding reveals a new concept for the design of a 3D-printed PCL/npW composite-based bone substitute for the early treatment of osteonecrosis defects.


Assuntos
Regeneração Óssea/efeitos dos fármacos , Fêmur/efeitos dos fármacos , Nanopartículas/administração & dosagem , Osteogênese/efeitos dos fármacos , Poliésteres/farmacologia , Tecidos Suporte/química , Animais , Caproatos/farmacologia , Diferenciação Celular/efeitos dos fármacos , Lactonas/farmacologia , Masculino , Células-Tronco Mesenquimais/efeitos dos fármacos , Osteonecrose/tratamento farmacológico , Impressão Tridimensional , Coelhos , Silicatos/farmacologia , Engenharia Tecidual/métodos , Microtomografia por Raio-X/métodos , Compostos de Zinco/farmacologia
14.
J Mater Chem B ; 9(39): 8289-8299, 2021 10 13.
Artigo em Inglês | MEDLINE | ID: mdl-34505617

RESUMO

While pulp capping using a variety of materials has been applied clinically to preserve the health and vitality of the dental pulp and induce dentin repair no material meets all the anti-infection, anti-inflammation, and promoting pulp tissue regeneration criteria. Micro-nano materials of bioactive glasses (BG) with the biocompatibility and osteogenesis-promoting properties were developed for this study using Zn-doped bioactive glass (BGz) micro-nano spheres for dental pulp capping to control infection and inflammation and promote tissue regeneration. Of three key findings, the co-culture of Porphyromonas gingivalis showed that the BGz had an excellent antibacterial effect, and after being stimulated with BGz in vitro, macrophages showed a significant decrease of pro-inflammatory M1 markers compared with the undoped BG group. It is also noted that the conditioned medium derived from BGz-stimulated macrophages could significantly promote mineralized dentin formation of dental pulp cells (DPCs). In rats, acute pulp restoration experiments proved that BGz used as a pulp capping agent had excellent dentin regenerative properties. This work may provide a novel strategy to promote osteo/dentinogenic differentiation through regulating early inflammation, with potential applications in pulp capping.


Assuntos
Compostos de Cálcio/farmacologia , Capeamento da Polpa Dentária , Dentina/fisiologia , Agentes de Capeamento da Polpa Dentária e Pulpectomia/farmacologia , Compostos de Silício/farmacologia , Compostos de Zinco/farmacologia , Animais , Anti-Infecciosos/química , Anti-Infecciosos/farmacologia , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Compostos de Cálcio/química , Polpa Dentária/citologia , Dentina/efeitos dos fármacos , Vidro , Camundongos , Porphyromonas gingivalis/efeitos dos fármacos , Agentes de Capeamento da Polpa Dentária e Pulpectomia/química , Células RAW 264.7 , Ratos , Compostos de Silício/química , Compostos de Zinco/química
15.
Med Oncol ; 38(11): 129, 2021 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-34550481

RESUMO

Zn(II) complex of Schiff base derived from the condensation of 4-aminopyrimidine-2(1H)-one with salicylaldehyde was prepared and characterized by various physico-chemical and spectral methods for structure determination. The cytotoxic activity of the Zn(II) complex was investigated in comparison with 5-fluorouracil (5-FU) against two different human brain tumor cell lines (T98G and U118), while primer human dermal fibroblast cells (HDF) was used as control for biocompatibility. Then, the effectiveness of electroporation (EP) on cytotoxic activities of these compounds has been examined. The cytotoxicities of the 5-FU and new Zn(II) complex, alone or in combination with electroporation, were determined by MTT assay. The Zn(II) complex showed good cytotoxicity against T98G and U118 brain tumor cell lines with IC50 = 282.47 and 297.91 µM respectively, while it was safe on HDF healthy cells with IC50 = 826.72 µM. The 5-FU exhibited less cytotoxicity compared to the Zn(II) complex against T98G (IC50 = 382.35 µM) and U118 (IC50 = 396.56 µM) tumor cell lines. The combined application of Zn (II) + EP decreased the IC50 value by 5.96-fold in T98G cells and 4.76-fold in U118 cells. EP showed a similar effect in its combined application with 5-FU, resulting in a decrease of the IC50 value of 4.22-fold in the T98G cells and 3.84-fold in the U118 cells. In a conclusion, the Zn(II) complex exhibited an anticancer potential against both brain tumor cell lines (T98G and U118) and EP greatly increased the cytotoxicity of Zn(II) complex and 5-FU on these chemotherapy-resistant cells.


Assuntos
Antineoplásicos/farmacologia , Neoplasias Encefálicas/tratamento farmacológico , Eletroporação , Fluoruracila/farmacologia , Compostos de Zinco/farmacologia , Neoplasias Encefálicas/patologia , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos , Eletroquimioterapia , Humanos , Compostos de Zinco/química
16.
Daru ; 29(2): 321-328, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34417987

RESUMO

PURPOSE: Mohs' paste, which is composed of zinc chloride and zinc oxide starch, is used for hemostasis of superficial malignancy in the clinical setting. We investigated the concentration of intramuscular zinc in mice after Mohs' paste application and evaluated its relationship with angiogenesis from the perspective of blood flow levels within 24 h. METHODS: Male C57BL/6JJmsSlc mice were administered single dose of Mohs' paste at 25%, 50%, and 75% after unilateral hind limb surgery, and glycerin, a viscosity modifier, was administered to the control group (0%). Hind limb blood flow levels were measured with a laser Doppler perfusion imaging system (n = 6). The amounts of intramuscular zinc and vascular endothelial growth factor-A (VEGF-A) expression were analyzed using inductively coupled plasma mass spectrometry (ICP-MS) and western blotting, respectively (n = 5 or 3). RESULTS: Blood flow levels were significantly decreased in the 50% group after 8 h, and significantly decreased in the 25% and 50% groups after 24 h. Intramuscular zinc was significantly increased in the 50% and 75% groups after 8 h. Western blotting showed that VEGF-A levels were significantly increased in the 25% and 50% groups after 8 h. Based on analytical experiments and biological investigation, we predicated the pharmacological effect of Mohs' paste and found over 50% of it is critical in the blood flow and angiogenesis suppression after more than 8 h of its application. CONCLUSIONS: The results suggest that the mechanism of blood flow suppression is independent of VEGF-A levels and might suppress future angiogenesis. Our findings support that of previous studies, in which Mohs' paste was expected to induce hemostasis and suppress angiogenesis. It is an excellent ointment that facilitates hemostasis by suppressing blood flow regardless of angiogenesis, and may be apt for situations where hemostasis is required in the clinical setting.


Assuntos
Inibidores da Angiogênese/administração & dosagem , Circulação Sanguínea/efeitos dos fármacos , Cloretos/administração & dosagem , Membro Posterior/cirurgia , Músculo Esquelético/química , Fator A de Crescimento do Endotélio Vascular/metabolismo , Compostos de Zinco/administração & dosagem , Zinco/análise , Inibidores da Angiogênese/química , Inibidores da Angiogênese/farmacologia , Animais , Cloretos/química , Cloretos/farmacologia , Relação Dose-Resposta a Droga , Glicerol/química , Membro Posterior/diagnóstico por imagem , Fluxometria por Laser-Doppler , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Músculo Esquelético/diagnóstico por imagem , Imagem de Perfusão , Espectrofotometria Atômica , Compostos de Zinco/química , Compostos de Zinco/farmacologia
17.
Int J Mol Sci ; 22(14)2021 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-34299039

RESUMO

Zinc chloride is known to be effective in combatting hepatitis A virus (HAV) infection, and zinc ions seem to be especially involved in Toll-like receptor (TLR) signaling pathways. In the present study, we examined this involvement in human hepatoma cell lines using a human TLR signaling target RT-PCR array. We also observed that zinc chloride inhibited mitogen-activated protein kinase kinase 3 (MAP2K3) expression, which could downregulate HAV replication in human hepatocytes. It is possible that zinc chloride may inhibit HAV replication in association with its inhibition of MAP2K3. In that regard, this study set out to determine whether MAP2K3 could be considered a modulating factor in the development of the HAV pathogen-associated molecular pattern (PAMP) and its triggering of interferon-ß production. Because MAP2K3 seems to play a role in antiviral immunity against HAV infection, it is a promising target for drug development. The inhibition of MAP2K3 may also prevent HAV patients from developing a severe hepatitis A infection.


Assuntos
Carcinoma Hepatocelular/virologia , Cloretos/farmacologia , Hepatite A/complicações , Hepatócitos/virologia , Neoplasias Hepáticas/virologia , MAP Quinase Quinase 3/antagonistas & inibidores , Replicação Viral , Compostos de Zinco/farmacologia , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/enzimologia , Hepatite A/virologia , Vírus da Hepatite A/isolamento & purificação , Hepatócitos/efeitos dos fármacos , Hepatócitos/enzimologia , Interações Hospedeiro-Patógeno , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/enzimologia , Células Tumorais Cultivadas
18.
Dalton Trans ; 50(28): 9700-9708, 2021 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-33950057

RESUMO

In this study, a new fluorinated phthalonitrile compound namely 5-bis[4-(trifluoromethoxy)-thiophenyl] phthalonitrile was synthesized. In addition, peripherally substituted symmetric metallated phthalocyanine derivatives [M = Co (2) and M = Zn (3)] and unsymmetrically substituted zinc phthalocyanine (ZnPc) complex (4) were synthesized by cyclotetramerization of this phthalonitrile compound. Characterization of all new compounds was carried out using FT-IR, NMR, UV-Vis, and mass spectroscopy. Additionally, antioxidant activity, DNA cleavage activity, antimicrobial activity, biofilm inhibition activity, and bacterial viability inhibition test of the compounds (1-4) were investigated. The antioxidant activities of the new phthalocyanine complexes were studied by performing two different methods. The results indicated that the highest DPPH (1,1-diphenyl-2-picrylhydrazyl) free radical scavenging activity was determined to be 67.85% for 2 and also 3 showed the highest activity with 31.65% for chelating activity at 200 mg L-1 concentration. Phthalocyanine compounds demonstrated effective DNA cleavage and antimicrobial activities. The highest percentage of cell vitality inhibition was found for compound 4, 56.92%. Also, test compounds exhibited good biofilm inhibition activity.


Assuntos
Anti-Infecciosos , Antioxidantes , Quelantes , Cobalto , Flúor , Isoindóis , Compostos Organometálicos , Compostos de Zinco , Anti-Infecciosos/química , Anti-Infecciosos/farmacologia , Antioxidantes/química , Antioxidantes/farmacologia , Bactérias/efeitos dos fármacos , Bactérias/genética , Biofilmes/efeitos dos fármacos , Compostos de Bifenilo/química , Candida albicans/efeitos dos fármacos , Candida albicans/crescimento & desenvolvimento , Quelantes/química , Quelantes/farmacologia , Cobalto/química , Cobalto/farmacologia , Clivagem do DNA , Flúor/química , Flúor/farmacologia , Ferro/química , Isoindóis/química , Isoindóis/farmacologia , Compostos Organometálicos/química , Compostos Organometálicos/farmacologia , Picratos/química , Compostos de Zinco/química , Compostos de Zinco/farmacologia
19.
J Oleo Sci ; 70(4): 541-548, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33814514

RESUMO

Two mixed-ligand complexes on the basis of L ligand [L = 3,6-bis(imidazol-1-yl)pyridazine] have been prepared under the solvothermal reaction conditions via the Zn(II) salts reacting with the ligands of L in the existence of two positional isomerous carboxylic acid ligands and their chemical formula respectively are [Zn5(L)(1,2-BDC)4(µ3-OH)2] n (1, 1,2-H2BDC = 1,2-benzenedicarboxylic acid ) and {[Zn4(L)2(1,3-HBDC) (1,3-BDC)(µ3-OH)4]·ClO4·3H2O} n (2, 1,3-H2BDC = 1,3-benzenedicarboxylic acid). The inhibitory influence of the two compounds against the inflammatory response in periodontium was evaluated by measuring the inflammatory cytokines releasing with ELISA detection kit. The results of ELISA assay indicated that compound 1 showed much stronger inhibitory influences than compound 2 against the inflammatory cytokines releasing. In addition to this, the suppression activity of the compounds against the survival gene of Porphyria gingivalis was detected via the real time Reverse Transcription-Polymerase Chain Reaction, and the results suggested that compound 1 could evidently suppresses the survival gene expression of Porphyria gingivalis, which is much better than the biological activity of compound 2. Above all, compound 1 was more outstanding than compound 2 on chronic periodontitis treatment by inhibiting the Porphyria gingivalis survival.


Assuntos
Fenômenos Fisiológicos Bacterianos/genética , Periodontite Crônica/tratamento farmacológico , Periodontite Crônica/microbiologia , Complexos de Coordenação/farmacologia , Complexos de Coordenação/uso terapêutico , RNA Polimerases Dirigidas por DNA/genética , RNA Polimerases Dirigidas por DNA/metabolismo , Expressão Gênica/efeitos dos fármacos , Genes Bacterianos/genética , Periodonto/metabolismo , Periodonto/microbiologia , Porfirias/genética , Compostos de Zinco/farmacologia , Compostos de Zinco/uso terapêutico , Animais , Complexos de Coordenação/química , Cristalização , Citocinas/metabolismo , Modelos Animais de Doenças , Cães , Ensaio de Imunoadsorção Enzimática , Mediadores da Inflamação/metabolismo , Conformação Molecular , Polímeros , Compostos de Zinco/química
20.
Molecules ; 26(7)2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33916013

RESUMO

Periodontal diseases like gingivitis and periodontitis are primarily caused by dental plaque. Several antiplaque and anti-microbial agents have been successfully incorporated into toothpastes and mouthwashes to control plaque biofilms and to prevent and treat gingivitis and periodontitis. The aim of this article was to review recent developments in the antiplaque, anti-gingivitis, and anti-periodontitis properties of some common compounds in toothpastes and mouthwashes by evaluating basic and clinical studies, especially the ones published in the past five years. The common active ingredients in toothpastes and mouthwashes included in this review are chlorhexidine, cetylpyridinium chloride, sodium fluoride, stannous fluoride, stannous chloride, zinc oxide, zinc chloride, and two herbs-licorice and curcumin. We believe this comprehensive review will provide useful up-to-date information for dental care professionals and the general public regarding the major oral care products on the market that are in daily use.


Assuntos
Antissépticos Bucais/análise , Antissépticos Bucais/química , Doenças Periodontais/prevenção & controle , Cremes Dentais/análise , Cremes Dentais/química , Anti-Infecciosos Locais/química , Anti-Infecciosos Locais/farmacologia , Cetilpiridínio/química , Cetilpiridínio/farmacologia , Cloretos/química , Cloretos/farmacologia , Humanos , Doenças Periodontais/etiologia , Doenças Periodontais/patologia , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Fluoreto de Sódio/química , Fluoreto de Sódio/farmacologia , Fluoretos de Estanho/análise , Fluoretos de Estanho/química , Fluoretos de Estanho/farmacologia , Compostos de Zinco/química , Compostos de Zinco/farmacologia
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