Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 56
Filtrar
1.
EXCLI J ; 23: 300-334, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38655092

RESUMO

Cutaneous Squamous Cell Carcinoma (cSCC) is a common and potentially fatal type of skin cancer that poses a significant threat to public health and has a high prevalence rate. Exposure to ultraviolet radiation on the skin surface increases the risk of cSCC, especially in those with genetic syndromes like xerodermapigmentosum and epidermolysis bullosa. Therefore, understanding the molecular pathogenesis of cSCC is critical for developing personalized treatment approaches that are effective in cSCC. This article provides a comprehensive overview of current knowledge of cSCC pathogenesis, emphasizing dysregulated signaling pathways and the significance of molecular profiling. Several limitations and challenges associated with conventional therapies, however, are identified, stressing the need for novel therapeutic strategies. The article further discusses molecular targets and therapeutic approaches, i.e., epidermal growth factor receptor inhibitors, hedgehog pathway inhibitors, and PI3K/AKT/mTOR pathway inhibitors, as well as emerging molecular targets and therapeutic agents. The manuscript explores resistance mechanisms to molecularly targeted therapies and proposes methods to overcome them, including combination strategies, rational design, and optimization. The clinical implications and patient outcomes of molecular-targeted treatments are assessed, including response rates and survival outcomes. The management of adverse events and toxicities in molecular-targeted therapies is crucial and requires careful monitoring and control. The paper further discusses future directions for therapeutic advancement and research in this area, as well as the difficulties and constraints associated with conventional therapies.

3.
Clin Immunol ; 259: 109898, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38185267

RESUMO

Myelin antigen-reactive Th1 and Th17 cells are critical drivers of central nervous system (CNS) autoimmune inflammation. Transcription factors T-bet and RORγt play a crucial role in the differentiation and function of Th1 and Th17 cells, and impart them a pathogenic role in CNS autoimmune inflammation. Mice deficient in these two factors do not develop experimental autoimmune encephalomyelitis (EAE). While T-bet and RORγt are known to regulate the expression of several cell adhesion and migratory molecules in T cells, their role in supporting Th1 and Th17 trafficking to the CNS is not completely understood. More importantly, once Th1 and Th17 cells reach the CNS, how the function of these transcription factors modulates the local inflammatory response during EAE is unclear. In the present study, we showed that myelin oligodendrocyte glycoprotein 35-55 peptide (MOG35-55)-specific Th1 cells deficient in RORγt could cross the blood-brain barrier (BBB) but failed to induce demyelination, apoptosis of neurons, and EAE. Pathogenic Th17 cell-derived cytokines GM-CSF, TNF-α, IL-17A, and IL-21 significantly increased the surface expression of IL-23R on neuronal cells. Furthermore, we showed that, in EAE, neurons in the brain and spinal cord express IL-23R. IL-23-IL-23R signaling in neuronal cells caused phosphorylation of STAT3 (Ser727 and Tyr705) and induced cleaved caspase 3 and cleaved poly (ADP-ribose) polymerase-1 (PARP-1) molecules in an IL-23R-dependent manner and caused apoptosis. Thus, we provided a mechanism showing that T-bet is required to recruit pathogenic Th17 cells to the CNS and RORγt-mediated inflammatory response to drive the apoptosis of IL-23R+ neurons in the CNS and cause EAE. Understanding detailed molecular mechanisms will help to design better strategies to control neuroinflammation and autoimmunity. ONE SENTENCE SUMMARY: IL-23-IL-23R signaling promotes apoptosis of CNS neurons.


Assuntos
Encefalomielite Autoimune Experimental , Camundongos , Animais , Células Th17 , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares/genética , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares/metabolismo , Camundongos Transgênicos , Células Th1 , Inflamação , Glicoproteína Mielina-Oligodendrócito , Fatores de Transcrição/metabolismo , Interleucina-23/metabolismo , Apoptose , Neurônios/metabolismo , Neurônios/patologia , Camundongos Endogâmicos C57BL
4.
ACS Omega ; 9(2): 2783-2794, 2024 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-38250361

RESUMO

The emergence of multidrug-resistant (MDR) bacteria has spurred the exploration of therapeutic nanomaterials such as ZnO nanoparticles. However, the inherent nonspecific toxicity of ZnO has posed a significant obstacle to their clinical utilization. In this research, we propose a novel approach to improve the selectivity of the toxicity of ZnO nanoparticles by impregnating them onto a less toxic clay mineral, Bentonite, resulting in ZB nanocomposites (ZB NCs). We hypothesize that these ZB NCs not only reduce toxicity toward both normal and carcinogenic cell lines but also retain the antibacterial properties of pure ZnO nanoparticles. To test this hypothesis, we synthesized ZB NCs by using a precipitation technique and confirmed their structural characteristics through X-ray diffraction and Raman spectroscopy. Electron microscopy revealed composite particles in the size range of 20-50 nm. The BET surface area of ZB NCs, within a relative pressure (P/P0) range of 0.407-0.985, was estimated to be 31.182 m2/g. Notably, 50 mg/mL ZB NCs demonstrated biocompatibility with HCT 116 and HEK 293 cell lines, supported by flow cytometry and fluorescence microscopy analysis. In vitro experiments further confirmed a remarkable five-log reduction in the population of MDR Escherichia coli in the presence of 50 mg/mL of ZB NCs. Antibacterial activity of the nanocomposites was also validated in the HEK293 and HCT 116 cell lines. These findings substantiate our hypothesis and underscore the effectiveness of ZB NCs against MDR E. coli while minimizing nonspecific toxicity toward healthy cells.

5.
J Leukoc Biol ; 115(2): 235-252, 2024 01 19.
Artigo em Inglês | MEDLINE | ID: mdl-37818891

RESUMO

Adaptive immune cells play an important role in mounting antigen-specific antitumor immunity. The contribution of innate immune cells such as monocytes, macrophages, natural killer (NK) cells, dendritic cells, and gamma-delta T cells is well studied in cancer immunology. NK cells are innate lymphoid cells that show effector and regulatory function in a contact-dependent and contact-independent manner. The cytotoxic function of NK cells plays an important role in killing the infected and transformed host cells and controlling infection and tumor growth. However, several studies have also ascribed the role of NK cells in inducing pathophysiology in autoimmune diseases, promoting immune tolerance in the uterus, and antitumor function in the tumor microenvironment. We discuss the fundamentals of NK cell biology, its distribution in different organs, cellular and molecular interactions, and its cytotoxic and noncytotoxic functions in cancer biology. We also highlight the use of NK cell-based adoptive cellular therapy in cancer.


Assuntos
Doenças Autoimunes , Neoplasias , Feminino , Humanos , Imunidade Inata , Células Matadoras Naturais , Neoplasias/terapia , Microambiente Tumoral
6.
Crit Rev Anal Chem ; : 1-15, 2023 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-37184105

RESUMO

In the present review article, different advanced liquid chromatographic techniques and the advanced techniques other than liquid chromatography that are used to estimate the pesticide residues from different plant-based samples are presented. In the beginning of the article, details of pesticides, their health effects and various cell lines used for the related study has been outlined. Afterward, detailed descriptions regarding pesticides classification are inscribed. In the end, recent advancements in the area of analysis of pesticides for herbal drugs are explained. Solid phase micro extraction (SPME) and solid-phase extraction (SPE) are considered as most common method of sample preparation for pesticides and its residual analysis. The most commonly used analytical separation technique for pesticide analysis is liquid chromatography (LC) integrated with mass spectrometry (MS) and MS/MS as Triple Quadrupole Mass Spectrometer (QqQ) for the samples analysis where high level of sensitivity and accuracy is required in quantification.

7.
Biotechnol Genet Eng Rev ; : 1-24, 2023 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-37243587

RESUMO

Staphylococcus aureus (S. aureus) has long been acknowledged as being one of the most harmful bacteria for human civilization. It is the main contributor to skin and soft tissue infections. The gram positive pathogen also contributes to bloodstream infections, pneumonia, or bone and joint infections. Hence, developing an efficient and targeted treatment for these illnesses is greatly desired. Recently, studies on nanocomposites (NCs) have significantly increased due to their potent antibacterial and antibiofilm properties. These NCs provide an intriguing way to control the growth of bacteria without causing the development of resistance strains that come from improper or excessive use of the conventional antibiotics. In this context, we have demonstrated the synthesis of a NC system by precipitation of ZnO nanoparticles (NPs) on Gypsum followed by encapsulation with Gelatine, in the present study. Fourier transform infrared (FTIR) spectroscopy was used to validate the presence of ZnO NPs and Gypsum. The film was characterized by X-ray diffraction (XRD) spectroscopy and scanning electron microscopy (SEM). The system exhibited promising antibiofilm action and was effective in combating S. aureus and MRSA in concentrations between 10 and 50 ug/ml. The bactericidal mechanism by release of reactive oxygen species (ROS) was anticipated to be induced by the NC system. Studies on cell survival and in-vitro infection support the film's notable biocompatibility and its potential for treating Staphylococcus infections in the future.

8.
Environ Res ; 216(Pt 4): 114700, 2023 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-36370814

RESUMO

Globally, Methicillin-Resistant Staphylococcus aureus bacteraemia is one of the commonest bloodstream infections associated with clinical complications and high mortality. Thence, devising effective and targeted biogenic silver based strategies are in great demand. However, limited insights regarding the biosynthesis methodologies impedes the possible scale up and commercial potentials. We, hereby demonstrate the biosynthesis of Ag nanoparticles using the phytochemical agent extracted and purified from bulb extract of Urginea indica. The chemical structure of the phytochemical agent is investigated by various chromatographic and spectroscopic techniques and was found closely relatable to N-ethylacetamide. Ag nanoparticles synthesis by this agent was found to have a strong Surface Plasmon band at 402 nm. X-ray diffraction and transmission electron microscopy further validated the formation of Ag nanoparticles with face-centred cubic structure with a size range of 20-30 nm. The biogenic metal nanoparticles have shown potential antibacterial activity against S. aureus and MRSA (within a range of 10-50 µg/mL). The nanoparticles have also shown promising anti-biofim activity against the above mentioned strains. The nanoparticles were expected to induce ROS mediated bactericidal mechamism. Cell viability and in-vitro infection studies advocate noticeable biocompatibility and future clinical potential of the developed nanoparticles against Staphylococcus infections.


Assuntos
Bacteriemia , Drimia , Nanopartículas Metálicas , Staphylococcus aureus Resistente à Meticilina , Infecções Estafilocócicas , Humanos , Prata/farmacologia , Prata/química , Nanopartículas Metálicas/química , Staphylococcus aureus , Testes de Sensibilidade Microbiana , Infecções Estafilocócicas/tratamento farmacológico , Antibacterianos/farmacologia , Antibacterianos/química , Compostos Fitoquímicos/farmacologia
9.
Biotechnol Genet Eng Rev ; : 1-35, 2022 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-36576250

RESUMO

Diabetes mellitus is a chronic endocrine disease that occurs mostly in the state of hyperglycemia (elevated blood glucose level). In the recent times, diabetes is listed under world's utmost critical health issues. Wound treatment procedures are complicated in diabetic individuals all over the world. Diabetic wound care not only involves high-cost, but also the primary cause of hospitalization, which can lead to amputation thereby reducing diabetic patient life expectancy. To lower the risk of amputation, wound healing requires the development of effective treatments. Traditional management systems for Diabetes are frequently chastised due to their high costs, difficulties in maintaining a sustainable supply chain and limited disposal alternatives. The worrisome rise in diabetes prevalence has sparked a surge of interest in the discovery of viable remedies to supplement existing treatments. Nanomaterials wound healing has a lot of potential for treating and preventing wound infections and it has recently gained popularity owing to its ability to transport drugs to the wound area in a regulated fashion, potentially overpowering the limits of traditional approaches. This research assessed several nanosystems, such as nanocarriers and nanotherapeutics, to explore how they can benefit in diabetic wound healing, with a focus on current obstacles and future prospects.

10.
Mol Biotechnol ; 64(12): 1454-1467, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35763198

RESUMO

Zanthoxylum armatum DC. is a plant with many medicinal values which is extensively used in traditional system of medicine for curing various diseases and ailments, including cancer. The aim of the present study is to identify Zanthoxylum armatum collected from different parts of Manipur, India, at molecular level. Molecular markers like internal transcribed spacer (ITS) region and other DNA barcoding genes such as matK, rbcL, psbA-trnH and trnL-trnF were targeted to find out the most suitable DNA barcode for identifying this species. Sequences obtained using the five primer pairs-ITS An5 and ITS An4, matK-413f-1 and matK-1227r-1, rbcL-1F and rbcL-724R, psbA-F and trnH-R and trnL-F and trnF-R were submitted to GenBank, NCBI. Amongst the five DNA barcoding targets, one nuclear and four chloroplast genes were successfully amplified by PCR (100%) and sequencing (100%) in all the eight plant samples. Sequence similarity of total ITS region (620 bp) when compared to the reference sequence were found to be between 98.55 and 99.68%. In our study, ITS sequence in combination with DNA barcoding sequences of rbcL, trnH-psbA and trnL-trnF was very successful in identification of Z. armatum and differentiate other species clearly in the phylogeny analysis. Our work shows ITS region to be the most suitable DNA barcode which formed a monophyletic group of the species in the phylogenetic tree analysis. The sequences of the barcoding genes of Z. armatum DC. obtained from this study adds to the already available resources which will be helpful in the future research endeavours.


Assuntos
Código de Barras de DNA Taxonômico , Zanthoxylum , DNA de Plantas/genética , DNA Ribossômico , DNA Espaçador Ribossômico/genética , Índia , Filogenia , Zanthoxylum/genética
11.
J Invest Dermatol ; 142(10): 2706-2714.e3, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35378114

RESUMO

γδ T cells represent a small fraction of total T cells in the body and do not use classical polymorphic major histocompatibility complex‒loaded peptides for mounting an immune response. The importance of the effector and regulatory function of γδ T cells in infections, autoimmunity, and tumor models are well characterized. In this study, we investigated the mechanistic role of γδ T cells in costimulatory blockade‒induced transplantation tolerance. We used donor-specific transfusion and anti-CD40L treatment in C57BL/6 mice to induce tolerance to BALB/c skin allografts. We show that depletion of γδ T cells, specifically Vγ2+ γδ T cells, led to the acute rejection of skin allografts despite tolerogen treatment. Tolerogen treatment promoted CD39+Vγ2+ γδ T cells and suppressed IFN-γ‒producing Vγ2+ γδ T cells in the spleen and allografts. Vγ2+ γδ T cells isolated from tolerized mice suppress T helper type 1 cell differentiation. Adoptive transfer of these regulatory Vγ2+ γδ T cells prolonged the survival of allografts in an untreated recipient and Tcrδ‒/‒ mice. Together, our data show that the Vγ2+ subset promotes costimulatory blockade‒induced survival of skin allografts and that tolerogenic Vγ2+ T cells can be used as an adoptive cellular therapy to promote the survival of allografts.


Assuntos
Inflamação , Linfócitos T , Aloenxertos , Animais , Rejeição de Enxerto/prevenção & controle , Sobrevivência de Enxerto , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Compostos Orgânicos , Transplante de Pele
12.
ACS Infect Dis ; 7(8): 2068-2072, 2021 08 13.
Artigo em Inglês | MEDLINE | ID: mdl-33779133

RESUMO

Antibacterial activity of silver nanoparticles is often associated with toxicity to the host. We here report that noncytotoxic doses of silver nanoparticles coated with zinc oxide, Ag@ZnO, can stimulate proliferation and migration of human keratinocytes, HaCaT, with increased expression of Ki67 and vinculin at the leading edge of wounds. Interestingly, Ag@ZnO stimulates keratinocytes to produce the antimicrobial peptides hBD2 and RNase7, promoting antibacterial activity against both extracellular and intracellular Staphylococcus aureus isolated from wounds. Overall, these results suggest that Ag@ZnO has the potential to significantly improve treatment outcomes in clearing wound infection.


Assuntos
Nanopartículas Metálicas , Óxido de Zinco , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Humanos , Queratinócitos , Proteínas Citotóxicas Formadoras de Poros , Prata
13.
Front Bioeng Biotechnol ; 9: 788527, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34976976

RESUMO

Chemotherapy side effects, medication resistance, and tumor metastasis impede the advancement of cancer treatments, resulting in a poor prognosis for cancer patients. In the last decade, nanoparticles (NPs) have emerged as a promising drug delivery system. Swertia chirayita has long been used as a treatment option to treat a variety of ailments. Zinc oxide nanoparticles (ZnO-NPs) were synthesized from ethanolic and methanolic extract of S. chirayita leaves. ZnO-NPs were characterized using UV-visible spectroscopy, Fourier transform infrared spectroscopy (FTIR), scanning electron Microscopy (SEM), high-resolution transmission electron microscopy (HRTEM), and X-ray diffraction (XRD). Its anti-cancer activities were analyzed using cytotoxicity assays [MTT assay and acridine orange (AO) staining] and quantitative real-time PCR (qRT-PCR) using colorectal cancer (CRC) cells (HCT-116 and Caco-2) and control cells (HEK-293). The ZnO-NPs synthesized from the ethanolic extract of S. chirayita have an average size of 24.67 nm, whereas those from methanolic extract have an average size of 22.95 nm with a spherical shape. MTT assay showed NPs' cytotoxic potential on cancer cells (HCT-116 and Caco-2) when compared to control cells (HEK-293). The IC50 values of ethanolic and methanolic extract ZnO-NPs for HCT-116, Caco-2, and HEK-293 were 34.356 ± 2.71 and 32.856 ± 2.99 µg/ml, 52.15 ± 8.23 and 63.1 ± 12.09 µg/ml, and 582.84 ± 5.26 and 615.35 ± 4.74 µg/ml, respectively. Acridine orange staining confirmed the ability of ZnO-NPs to induce apoptosis. qRT-PCR analysis revealed significantly enhanced expression of E-cadherin whereas a reduced expression of vimentin and CDK-1. Altogether, these results suggested anti-cancer properties of synthesized ZnO-NPs in CRC.

14.
Curr Res Immunol ; 2: 66-78, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35492389

RESUMO

Neurokinin receptors belong to the GPCRs family and are ubiquitously expressed throughout the nervous and immune systems. Neurokinin receptors in coordination with neurokinins playing an important role in many physiological processes, including smooth muscle contraction, secretion, proliferation, and nociception. They also contribute to various disease conditions such as inflammatory bowel disease, rheumatoid arthritis, multiple sclerosis, psoriasis, and cancer. Neurokinin receptors antagonist are potent and highly selective and showing success in treating chemotherapy-induced nausea and vomiting. In this review, discuss the various neurokinin receptor expression on immune cells and their importance in various inflammatory and autoimmune diseases and their therapeutic importance.

15.
Environ Res ; 187: 109620, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32416355

RESUMO

Microbial contamination of water is one of the major sources of many diseases worldwide. Evolution of antibacterial resistance (ABR) alongside the caveats in most of the water treatment methods causes the severity of the current problem extremely vexing. This calls for an urgent need to develop new treatment methods aiming to reduce the microbial as well as ABR load in the environment. Herein, we successfully developed a visible light assisted sonophotocatalysis (SPC) using Fe/ZnO nanoparticles (NPs) for the disinfection of Shigella dysenteriae. A consortia containing S. dysenteriae and S. flexineri was also completely disinfected using SPC. Growth conditions of S. dysenteriae like growth phases and growth temperaturehad different outcomes on the overall efficacy of SPC. Compared with catalysts such as ZnO and TiO2, Fe/ZnO resulted in better disinfection. Multi-ROS production, mostly containing h+ and O2· radicals, due to the electron displacement in the catalyst and acoustic cavitation was identified as the factors behind bacterial lethality. The ROS produced was found to interfere with the metabolic activities of S. dysenteriae by causing membrane perturbation. We identified DNA damage inside the cells and the subsequent release of intracellular components. The compositional changes in the fatty acid makeup of the cells were altered as a result of SPC and few fatty acid markers indicating the stress posed by SPC were also identified. Loss of ABR in S. dysenteriae was also recorded post SPC treatment. Abatement in the biofilm forming ability of the injured bacterial cells was also recorded, proving the extremity of stress induced by SPC. Hence, the excellent efficacy of SPC in disinfecting bacteria is proposed for tertiary water treatment applications.


Assuntos
Desinfecção , Shigella , Antibacterianos/farmacologia , Biofilmes , Luz
16.
Colloids Surf B Biointerfaces ; 189: 110846, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32066090

RESUMO

Rapid increase in the case of bacterial infections is considered as a major public health concern and hence exploration of alternative treatment procedures including development of nanomaterials based therapeutic strategies is receiving much attention. In this aspect, here we investigated the antibacterial efficacy of a simple and potential metal/metal oxide nanocomposite system. Biogenic synthetic protocol was designed for processing of Ag/CaO nanocomposites (NCs). Structural features and morphology of the synthesized nanomaterials were investigated by X-ray diffraction (XRD) and electron microscopy techniques respectively. Optical properties of the nanomaterials were analyzed by UV-vis spectrophotometer. Presence of water and possible impurity molecules on the materials surface was examined by Fourier-transform infrared spectroscopy (FTIR). Effective antibacterial activity of the NCs was observed (within a range of 25-150 µg/mL of NCs) against Staphylococcus aureus (S. aureus) and Methicillin-resistant Staphylococcus aureus (MRSA). The potential anti-biofilm effect of as synthesized NCs was tested against S. aureus. Experimental results suggest that the antibacterial action of the NCs could be due to the induction of reactive oxygen species (ROS). DNA degradation and change in the bacterial cell membrane has further indicated the complete disinfection of the target bacterial system. The cytotoxicity evaluation has confirmed that the formation of NCs has maintained the antibacterial efficacy of Ag NPs but reduced its toxicity towards mammalian cells.


Assuntos
Antibacterianos/farmacologia , Compostos de Cálcio/farmacologia , Nanocompostos/química , Óxidos/farmacologia , Prata/farmacologia , Staphylococcus aureus/efeitos dos fármacos , Animais , Antibacterianos/química , Biofilmes/efeitos dos fármacos , Compostos de Cálcio/química , Sobrevivência Celular/efeitos dos fármacos , DNA Bacteriano/efeitos dos fármacos , DNA Bacteriano/metabolismo , Células HCT116 , Humanos , Camundongos , Óxidos/química , Tamanho da Partícula , Células RAW 264.7 , Espécies Reativas de Oxigênio/metabolismo , Prata/química , Staphylococcus aureus/metabolismo , Propriedades de Superfície
17.
Curr Drug Discov Technol ; 17(1): 23-29, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-30306873

RESUMO

OBJECTIVE: Aripiprazole, a synthetic compound, obtained by chemical modification of the structure of quinolinone is considered as an atypical antipsychotic drug. The present review is an attempt to summarize the updated information related to reported chemistry and pharmacology of Aripiprazole. DEVELOPMENT: Aripiprazole, under development by Otsuka Pharmaceutical, was approved by the U.S. Food and Drug Administration (USFDA) by the end of 2002 with an aim to treat patients with schizophrenia. This drug got approved by European Commission in February 2013 to treat the patients having severe manic episodes in bipolar I disorder Additionally, it got approval in Japan in January 2006 and in Canada in 2014. Pharmacology: Aripiprazole shows high specificity for dopamine receptor especially D2 and D3, serotonin 5-HT1A and serotonin 5-HT2A receptors, reasonable specificity for dopamine D4, serotonin 5- HT2C and 5-HT7, alpha1-adrenergic and histamine H1 receptors. It also shows moderate specificity for the serotonin reuptake. The major side effects include headache, agitation, akithesia, anxiety, tachycardia, insomnia, postural hypotension, constipation, vomiting, dizziness, nervousness and somnolence. CONCLUSION: The present article embarks the available information on Aripiprazole with emphasis on its clinical pharmacology, mechanism of action, pharmacokinetics, pharmacodynamics, metabolism and clinical trials.


Assuntos
Antipsicóticos/farmacologia , Aripiprazol/farmacologia , Esquizofrenia/tratamento farmacológico , Antipsicóticos/uso terapêutico , Aripiprazol/uso terapêutico , Aprovação de Drogas , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento , Estados Unidos , United States Food and Drug Administration/legislação & jurisprudência
18.
J Immunother Cancer ; 7(1): 208, 2019 08 06.
Artigo em Inglês | MEDLINE | ID: mdl-31387637

RESUMO

BACKGROUND: NKT cells play an important role in anti-tumor immunity. Alpha-galactosylceramide (α-GalCer), a synthetic glycolipid is presented to natural killer T (NKT) cells by most antigen-presenting cells through CD1d molecules leading to activation of NKT cells. However, the precise mechanisms of how α-GalCer-activated NKT regulate the polarization of the macrophages and effector T cells in the solid tumor are not studied adequately. METHODS: We induced solid tumor in C57BL/6 mice by subcutaneous injection of B16F10 cell line (1 X 106 cells) and monitored the tumor growth. Animals were given an intraperitoneal injection of α-GalCer (2 µg/injection) in 200 µl PBS on day + 1, + 5, + 10, + 15, and + 20 (with respect to tumor cell injection). Immune cells were characterized using flow cytometry and immunofluorescence staining. NK cells, Gr1+ cells, and F4/80+ macrophages in the mice were depleted by intravenous injection of cell-specific antibodies. Statistical analysis was performed using Student's t-test or one-way ANOVA. RESULTS: Our results showed that intratumoral NKT cells have a lower frequency of CD69, CD25, CD122, and IFN-γR expression; produced less inflammatory cytokines such as IFN-γ, TNF-α, and GM-CSF; higher frequency CD62L+ NKT cells; and also showed reduced proliferation as compared to the splenic NKT cells. Mice treated with α-GalCer showed a significantly increased frequency of IFN-γ-producing NKT cells, CD8+ T cells, and effector Th1 cells. Depletion of NK cells in α-GalCer-treated mice showed a lower frequency of IFN-γ-producing CD4+ and CD8+ T cells in the tumor and prevented the α-GalCer-induced tumor growth. NKT cell activation with α-GalCer treatment significantly increased the iNOS+CD206- M1-macrophages and reduced the iNOS-CD206+ M2-macrophages in the spleen and tumor, and depletion of F4/80+ macrophages prevented the α-GalCer-induced reduction in the tumor growth. CONCLUSIONS: We showed that activation of NKT cell with α-GalCer modulates the frequency of M1-macrophages and effector Th1 cells in the secondary lymphoid tissues and tumor microenvironment and inhibit tumor growth. The finding suggests that activation of NKT cells with α-GalCer may provide an effective anti-cancer outcome.


Assuntos
Lectinas Tipo C/imunologia , Macrófagos/imunologia , Lectinas de Ligação a Manose/imunologia , Células T Matadoras Naturais/imunologia , Óxido Nítrico Sintase Tipo II/imunologia , Receptores de Superfície Celular/imunologia , Animais , Lectinas Tipo C/metabolismo , Ativação Linfocitária , Macrófagos/enzimologia , Macrófagos/metabolismo , Masculino , Receptor de Manose , Lectinas de Ligação a Manose/metabolismo , Melanoma Experimental/enzimologia , Melanoma Experimental/imunologia , Melanoma Experimental/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Células T Matadoras Naturais/enzimologia , Células T Matadoras Naturais/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Receptores de Superfície Celular/metabolismo , Microambiente Tumoral/imunologia
19.
Med Microbiol Immunol ; 208(5): 609-629, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30291475

RESUMO

The aim of the present study is focused on the synthesis of Au@ZnO core-shell nanocomposites, where zinc oxide is overlaid on biogenic gold nanoparticles obtained from Hibiscus Sabdariffa plant extract. Optical property of nanocomposites is investigated using UV-visible spectroscopy and crystal structure has been determined using X-ray crystallography (XRD) technique. The presence of functional groups on the surface of Au@ZnO core-shell nanocomposites has been observed by Fourier transforms infrared (FTIR) spectroscopy. Electron microscopy studies revealed the morphology of the above core-shell nanocomposites. The synthesized nanocomposite material has shown antimicrobial and anti-biofilm activity against Staphylococcus aureus and Methicillin Resistant Staphylococcus haemolyticus (MRSH). The microbes are notorious cross contaminant and are known to cause infection in open wounds. The possible antimicrobial mechanism of as synthesized nanomaterials has been investigated against Staphylococcus aureus and obtained data suggests that the antimicrobial activity could be due to release of reactive oxygen species (ROS). Present study has revealed that surface varnishing of biosynthesized gold nanoparticles through zinc oxide has improved its antibacterial proficiency against Staphylococcus aureus, whereas reducing its toxic effect towards mouse fibroblast cells under normal and hyperglycaemic condition. Further studies have been performed in mice model to understand the wound healing efficiency of Au@ZnO nanocomposites. The results obtained suggest the possible and effective use of as synthesized core shell nanocomposites in wound healing.


Assuntos
Antibacterianos/administração & dosagem , Fibroblastos/efeitos dos fármacos , Nanocompostos/administração & dosagem , Staphylococcus aureus/efeitos dos fármacos , Cicatrização/efeitos dos fármacos , Animais , Antibacterianos/efeitos adversos , Antibacterianos/isolamento & purificação , Modelos Animais de Doenças , Ouro/administração & dosagem , Ouro/efeitos adversos , Ouro/isolamento & purificação , Hibiscus/química , Camundongos , Nanocompostos/efeitos adversos , Extratos Vegetais/química , Infecções Estafilocócicas/prevenção & controle , Staphylococcus haemolyticus/efeitos dos fármacos , Óxido de Zinco/administração & dosagem , Óxido de Zinco/efeitos adversos , Óxido de Zinco/isolamento & purificação
20.
Artigo em Inglês | MEDLINE | ID: mdl-30388857

RESUMO

Antibiotic residues in the aquatic environment have the potential to induce resistance in environmental bacteria, which ultimately might get transferred to pathogens making treatment of diseases difficult and poses a serious threat to public health. If antibiotic residues in the environment could be eliminated or reduced, it could contribute to minimizing antibiotic resistance. Towards this objective, water containing ciprofloxacin was treated by sunlight-assisted photocatalysis using Fe- doped ZnO nanoparticles for assessing the degradation potential of this system. Parameters like pH, temperature, catalytic dosage were assessed for the optimum performance of the system. To evaluate degradation of ciprofloxacin, both spectrophotometric as well as microbiological (loss of antibiotic activity) methods were employed. 100 mg/L Fe-doped ZnO nanoparticle catalyst and sunlight intensity of 120,000⁻135,000 lux system gave optimum performance at pH 9 at 30 °C and 40 °C. Under these conditions spectrophotometric analysis showed complete degradation of ciprofloxacin (10 mg/L) at 210 min. Microbiological studies showed loss of antibacterial activity of the photocatalytically treated ciprofloxacin-containing water against Staphylococcus aureus (108 CFU) in 60 min and for Escherichia coli (108 CFU) in 75 min. The developed system, thus possess a potential for treatment of antibiotic contaminated waters for eliminating/reducing antibiotic residues from environment.


Assuntos
Antibacterianos/química , Catálise , Ciprofloxacina/química , Resíduos de Drogas/química , Nanopartículas/química , Luz Solar , Poluentes Químicos da Água/química , Purificação da Água/métodos , Óxido de Zinco/química
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA