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1.
Mol Biol Rep ; 51(1): 408, 2024 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-38460043

RESUMO

BACKGROUND: To describe an oncolytic adenovirus (OAd) encoding SP-SA-E7-4-1BBL that is capable of inducing tumor regression in therapeutic assays. Herein, we tested whether the antitumor effect is given by the induction of a tumor-specific immune response, as well as the minimum dose needed to elicit antitumor protection and monitor the OAd biodistribution over time. METHODS AND RESULTS: C57BL/6 mice (n = 5) per group were immunized twice with OAds encoding SP-SA-E7-4-1BBL, SA-E7-4-1BBL, or SP-SA-4-1BBL and challenged with TC-1 cancer cells. The DNA construct SP-SA-E7-4-1BBL was employed as a control via biolistic or PBS injection. Groups without tumor development at 47 days were rechallenged with TC-1 cells, and follow-up lasted until day 90. The minimum dose of OAd to induce the antitumor effect was established by immunization using serial dilution doses. The cytometry bead assay and the ELISpot assay were used to evaluate cytokine release in response to ex vivo antigenic stimulation. The distribution profile of the OAd vaccine was evaluated in the different organs by histological, immunohistochemical and qPCR analyses. The OAd SP-SA-E7-4-1BBL-immunized mice did not develop tumors even in a rechallenge. A protective antitumor effect was observed from a dose that is one hundredth of most reports of adenoviral vaccines. Immunization with OAd increases Interferon-gamma-producing cells in response to antigen stimulation. OAd was detected in tumors over time, with significant morphological changes, contrary to nontumor tissues. CONCLUSIONS: The OAd SP-SA-E7-4-1BBL vaccine confers a prophylactic, safe, long-lasting, and antigen-dependent antitumor effect mediated by a Th1 antitumor immune response.


Assuntos
Vacinas Anticâncer , Neoplasias , Animais , Camundongos , Papillomavirus Humano 16 , Ligante 4-1BB/genética , Ligante 4-1BB/farmacologia , Distribuição Tecidual , Camundongos Endogâmicos C57BL , Adenoviridae/genética , Imunidade , Neoplasias/terapia
2.
Curr Issues Mol Biol ; 45(1): 593-603, 2023 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-36661525

RESUMO

ZO-1α+ and ZO-1α- proteins are expressed in hermetic and leaky tight junctions, respectively. Two cis-acting distant exonic elements partly activate the 240 nucleotide-long α exon producing the ZO-1α+ isoform. However, the elements within and around the α exon and their respective factors involved in its splicing are unknown. To study the dynamic interaction between SRSF3 and its bioinformatically predicted target sites around the 3'ss upstream of the α exon during its activation, we performed EMSA, crosslinking, and in vivo splicing assays by ZO-1 minigene expression and siRNA-mediated silencing in transfected cells. Using V1 RNase, we probed the possible formation of a hairpin RNA structure between the intronic and proximal exonic SRSF3 binding sites. The hairpin sufficed for complex formations in the EMSA. The interaction of SRSF3 with the intronic site promoted the cooperative binding of SRSF3 to the exonic site. Finally, SRSF3 restored α exon activation in SRSF3 knockdown transfectants. Altogether, our results show that SRSF3-hairpin RNA interaction is crucial in the early recognition of 3'ss for α exon activation. It remains to be explored whether SRSF3 recruits or stabilizes the binding of other factors or brings separate splice sites into proximity.

3.
Cell Mol Biol (Noisy-le-grand) ; 69(15): 26-37, 2023 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-38279502

RESUMO

Chronic diseases are a worldwide health problem directly related to society, lifestyle, and the development of unhealthy habits over time. Cardiovascular disease, cancer, chronic respiratory disease, and diabetes are the main causes of death. Environmental factors, such as air pollutants, poor diet, genetic predisposition, or a combination of these, are related to the development of these diseases. These factors activate cell mechanisms, such as DNA damage, oxidative stress, endoplasmic reticulum stress, autophagy, inflammation, and cell death. Depending on the dose and duration of exposure to causative agents, this cell damage can be acute or chronic. Activating these cell mechanisms can rescue normal cell function and cause permanent damage, unleashing the degeneration of tissues and organs over time. A wide variety of treatments help control chronic diseases; however, they cannot be cured completely. This fact leads to complications, dysfunctions, and disabilities. Herein, we discuss some of the principal mechanisms involved and how cellular stress can lead to these diseases when they persist for a long time.


Assuntos
Estresse do Retículo Endoplasmático , Estresse Oxidativo , Humanos , Doença Crônica , Inflamação , Morte Celular , Autofagia
4.
Chem Biodivers ; 20(10): e202300463, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37531499

RESUMO

Over the last decade, liver diseases have become a global problem, with approximately two million deaths per year. The high increase in the mortality rate of these diseases is mostly related to the limitations in the understanding of the evolutionary clinical cases of liver diseases, the low delivery of drugs in the liver, the non-specific administration of drugs, and the side effects generated at the systemic level by conventional therapeutic agents. Today it is common knowledge that phytochemicals have a high curative potential, even in the prevention and/or reversibility of liver disorders; however, even using these green molecules, researchers continue to deal with the same challenges implemented with conventional therapeutic agents, which limits the pharmacological potential of these friendly molecules. On the other hand, the latest advances in nanotechnology have proven that the use of nanocarriers as a delivery system for green active ingredients, as well as conventional ones, increases the pharmacological potential of these active ingredients due to their physicochemical characteristics (size, Zeta potential, etc.,) moldable depending on the therapeutic objective; in addition to the above, it should be noted that in recent years, nanoparticles have been developed for the specific delivery of drugs towards a specific target (stellar cells, hepatocytes, Kupffer cells), depending on the clinical state of the disease in the patient. The present review addresses the challenges of traditional medicine and green nanomedicine as alternatives in the treatment of liver diseases.

5.
Int J Mol Sci ; 24(2)2023 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-36674772

RESUMO

Biometals are all metal ions that are essential for all living organisms. About 40% of all enzymes with known structures require biometals to function correctly. The main target of damage by biometals is the central nervous system (CNS). Biometal dysregulation (metal deficiency or overload) is related to pathological processes. Chronic occupational and environmental exposure to biometals, including iron and copper, is related to an increased risk of developing Parkinson's disease (PD). Indeed, biometals have been shown to induce a dopaminergic neuronal loss in the substantia nigra. Although the etiology of PD is still unknown, oxidative stress dysregulation, mitochondrial dysfunction, and inhibition of both the ubiquitin-proteasome system (UPS) and autophagy are related to dopaminergic neuronal death. Herein, we addressed the involvement of redox-active biometals, iron, and copper, as oxidative stress and neuronal death inducers, as well as the current metal chelation-based therapy in PD.


Assuntos
Doença de Parkinson , Oligoelementos , Humanos , Doença de Parkinson/patologia , Cobre , Metais , Ferro , Estresse Oxidativo , Oxirredução , Neurônios Dopaminérgicos/patologia , Quelantes/farmacologia , Quelantes/uso terapêutico
6.
Int Arch Allergy Immunol ; 182(4): 277-291, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33147596

RESUMO

INTRODUCTION: The use of probiotics has been broadly popularized due to positive effects in the attenuation of aberrant immune responses such as asthma. Allergic asthma is a chronic respiratory disease characterized by airway inflammation and remodelling. OBJECTIVE: This study was aimed to evaluate the effect of oral administration of Lactococcus lactis NZ9000 on asthmatic airway inflammation and lung tissue remodelling in rats and its relation to the maintenance of an adequate intestinal barrier. METHODS: Wistar rats were ovalbumin (OVA) sensitized and challenged and orally treated with L. lactis. Lung inflammatory infiltrates and cytokines were measured, and remodelling was evaluated. Serum OVA-specific immunoglobulin (Ig) E levels were assessed. We also evaluated changes on intestinal environment and on systemic immune response. RESULTS: L. lactis diminished the infiltration of proinflammatory leucocytes, mainly eosinophils, in the bronchoalveolar compartment, decreased lung IL-4 and IL-5 expression, and reduced the level of serum allergen-specific IgE. Furthermore, L. lactis prevented eosinophil influx, collagen deposition, and goblet cell hyperplasia in lung tissue. In the intestine, L. lactis-treated asthmatic rats increased Peyer's patch and goblet cell quantity and mRNA expression of IgA, MUC-2, and claudin. Additionally, intestinal morphological alterations were normalized by L. lactis administration. Splenocyte proliferative response to OVA was abolished, and serum levels of transforming growth factor (TGF)-ß were increased by L. lactis treatment. CONCLUSIONS: These findings suggest that L. lactis is a potential candidate for asthma prevention, and the effect is mediated by the improvement of intestinal barrier function and systemic TGF-ß production.


Assuntos
Remodelação das Vias Aéreas , Asma/metabolismo , Asma/patologia , Mucosa Intestinal/metabolismo , Mucosa Intestinal/microbiologia , Lactococcus lactis/fisiologia , Probióticos/administração & dosagem , Fator de Crescimento Transformador beta/biossíntese , Remodelação das Vias Aéreas/imunologia , Animais , Asma/etiologia , Asma/prevenção & controle , Citocinas/metabolismo , Modelos Animais de Doenças , Imunoglobulina E/sangue , Imunoglobulina E/imunologia , Mediadores da Inflamação/metabolismo , Leucócitos/imunologia , Leucócitos/metabolismo , Ovalbumina/imunologia , Ratos
7.
Int J Mol Sci ; 22(12)2021 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-34207500

RESUMO

The ability of tumor cells to evade the immune system is one of the main challenges we confront in the fight against cancer. Multiple strategies have been developed to counteract this situation, including the use of immunostimulant molecules that play a key role in the anti-tumor immune response. Such a response needs to be tumor-specific to cause as little damage as possible to healthy cells and also to track and eliminate disseminated tumor cells. Therefore, the combination of immunostimulant molecules and tumor-associated antigens has been implemented as an anti-tumor therapy strategy to eliminate the main obstacles confronted in conventional therapies. The immunostimulant 4-1BBL belongs to the tumor necrosis factor (TNF) family and it has been widely reported as the most effective member for activating lymphocytes. Hence, we will review the molecular, pre-clinical, and clinical applications in conjunction with tumor-associated antigens in antitumor immunotherapy, as well as the main molecular pathways involved in this association.


Assuntos
Ligante 4-1BB/imunologia , Antígenos de Neoplasias/imunologia , Imunidade Inata , Ativação Linfocitária , Proteínas de Neoplasias/imunologia , Neoplasias/imunologia , Animais , Humanos , Neoplasias/patologia , Neoplasias/terapia
8.
Acta Vet Hung ; 68(4): 374-379, 2021 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-33459615

RESUMO

The Wilms' tumour gene (WT1) has previously been described as an oncogene in several neoplasms of humans, including melanoma, and its expression increases cancer cell proliferation. Recent reports associate the expression of the PPARß/δ gene (peroxisome proliferator-activated receptor beta/delta) with the downregulation of WT1 in human melanoma and murine melanoma cell lines. The aim of this work was to analyse the expression of WT1 and its association with PPARß/δ in samples of healthy and melanoma-affected skin of horses by immunohistochemistry. WT1 protein expression was detected in healthy skin, mainly in the epidermis, hair follicle, sebaceous gland and sweat gland, while no expression was observed in equine melanoma tissues. Moreover, it was observed that PPARß/δ has a basal expression in healthy skin and that it is overexpressed in melanoma. These results were confirmed by a densitometric analysis, where a significant increase of the WT1-positive area was observed in healthy skin (128.66 ± 19.84 pixels 106) compared with that observed in melanoma (1.94 ± 0.04 pixels 106). On the other hand, a positive area with an expression of PPARß/δ in healthy skin (214.94 ± 11.85 pixels 106) was significantly decreased compared to melanoma (624.86 ± 181.93 pixels 106). These data suggest that there could be a regulation between WT1 and PPARß/δ in this disease in horses.


Assuntos
Doenças dos Cavalos , Melanoma , PPAR delta , PPAR beta , Doenças dos Roedores , Animais , Genes do Tumor de Wilms , Cavalos , Melanoma/genética , Melanoma/veterinária , Camundongos , PPAR delta/genética , PPAR beta/genética , Pele
9.
Adv Skin Wound Care ; 33(4): 1-7, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32195729

RESUMO

OBJECTIVE: Several studies suggest that pirfenidone may have a potential off-label use for wound healing. However, the effectiveness of this medication in patients with burns remains uncertain. Accordingly, investigators sought to assess wound re-epithelialization in patients with second-degree burns after adding pirfenidone to usual care. DESIGN AND SETTING: Single-center pilot, proof-of-concept, single-blind randomized controlled trial. PATIENTS AND INTERVENTION: Eight patients with second-degree burns were treated with occlusive hydrocolloid dressings and were randomly allocated to receive either no additional treatment or pirfenidone. OUTCOME MEASURES: The primary outcome of the study was to evaluate wound healing between groups based on the thickness of the re-epithelialized epidermis at day 7. Secondary outcomes were to qualitatively assess the development of fibrotic tissue in the dermis, anomalies in the basal membrane, and the development of collagen fibers by histologic analysis. Liver and renal functions were measured daily to assess the overall safety of oral pirfenidone. MAIN RESULTS: Patients treated with pirfenidone showed a remarkable improvement in wound re-epithelialization at day 7 (148.98 ± 13.64 vs 119.27 ± 15.55 µm; P = .029; 95% confidence interval, 4.14-55.29). Histologic evaluations showed less wound fibrosis in the pirfenidone group. CONCLUSIONS: A decrease in wound healing time by enhancing wound re-epithelialization was observed with pirfenidone. Larger clinical trials are needed to reach more reliable conclusions.


Assuntos
Anti-Infecciosos Locais/uso terapêutico , Anti-Inflamatórios não Esteroides/uso terapêutico , Queimaduras/terapia , Curativos Oclusivos/estatística & dados numéricos , Cicatrização/fisiologia , Administração Cutânea , Adulto , Queimaduras/tratamento farmacológico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reepitelização , Método Simples-Cego , Resultado do Tratamento
10.
Cell Biol Int ; 43(6): 706-714, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30977573

RESUMO

Early exposure to lead (Pb) has been associated with an elevated risk of developing neurodegenerative diseases. There is evidence that neuronal damage in chronic Pb exposure can be caused by the convergence of glial damage. Apoptosis may be a possible mechanism of Pb-induced cell death in the central nervous system. We tested cellular damage and apoptosis in the spinal cord of Wistar rats treated with Pb. Twelve rats were divided into two groups (n = 6): the control group was treated with only drinking water and the other group received 500 ppm of Pb acetate. After 3 months of Pb treatment, all animals were euthanized and spinal cords were extracted. Morphology was evaluated by Nissl and Kluver-Barrera stainings. Apoptosis was detected by terminal deoxynucleotidyl transferase dUTP nick end labeling assay. Specific antibodies were used to evaluate Pb damage in oligodendrocytes, astrocytes, and microglia. A large number of apoptotic bodies was observed in the white matter of the Pb-treated group. The Pb-treated group also showed a reduced number of neurons and oligodendrocytes but had an increased number of astrocytes compared with the nontreated group. Our results demonstrate that chronic Pb treatment induces neurodegeneration, demyelination, and astrogliosis in the rat spinal cord.


Assuntos
Intoxicação por Chumbo/metabolismo , Chumbo/efeitos adversos , Medula Espinal/efeitos dos fármacos , Animais , Apoptose/fisiologia , Astrocitoma/metabolismo , Astrocitoma/fisiopatologia , Morte Celular/fisiologia , Doenças Desmielinizantes/metabolismo , Doenças Desmielinizantes/fisiopatologia , Masculino , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Oligodendroglia/efeitos dos fármacos , Ratos , Ratos Wistar , Medula Espinal/metabolismo , Medula Espinal/fisiopatologia
11.
Cell Biol Int ; 43(7): 809-819, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31050073

RESUMO

Our research group has developed a cell-penetrating peptide-based delivery system that includes the Asn194Lys mutation in the rabies virus glycoprotein-9R peptide (mRVG-9R). This system has the capacity to deliver DNA in astrocytes and SH-SY5Y cells. The aim of this study was to evaluate the ability of the mRVG-9R peptide to deliver DNA molecules to murine brain cells. The mRVG-9R peptide, a karyophilic peptide (KP) and a plasmid encoding green fluorescent protein (GFP) were bound by electrostatic charges to form the mRVG-9R complex. mRVG-9R complex was injected into the cerebral cortex, striatum and hippocampus of C57BL/6 mice by stereotactic surgery. After 2, 4, and 20 days, the animals were sacrificed and their brains were prepared for quantitative reverse-transcription polymerase chain reaction and histological analysis. We detected the GFP expression in neurons and glial cells in the cerebral cortex, striatum, and hippocampus of the murine brain. The results suggest that the mRVG-9R peptide has the ability to deliver DNA molecules to murine brain cells. Also, the expression of the reporter gene is maintained at least up to 20 days after injection in neurons, astrocytes, oligodendrocytes, and microglia cells. Thus, the in vivo transfection ability of the mRVG-9R peptide, makes it a promising candidate as a therapeutic gene delivery vector to the central nervous system cells.


Assuntos
Peptídeos Penetradores de Células/farmacologia , Corpo Estriado/efeitos dos fármacos , Portadores de Fármacos/farmacologia , Glicoproteínas/farmacologia , Proteínas de Fluorescência Verde/metabolismo , Hipocampo/efeitos dos fármacos , Fragmentos de Peptídeos/farmacologia , Proteínas Virais/farmacologia , Animais , Astrócitos/citologia , Astrócitos/efeitos dos fármacos , Corpo Estriado/citologia , Genes Reporter , Vetores Genéticos/uso terapêutico , Proteínas de Fluorescência Verde/genética , Hipocampo/citologia , Camundongos , Camundongos Endogâmicos C57BL , Microglia/citologia , Neurônios/citologia , Neurônios/efeitos dos fármacos , Oligodendroglia/citologia , Oligodendroglia/efeitos dos fármacos , Transfecção/métodos
13.
Cancer Invest ; 36(1): 19-27, 2018 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-29388837

RESUMO

Conditionally replicative adenoviruses (CRAds) replicate poorly in murine cancer cells; however, E1b-deleted CRAds may replicate effectively in HPV16-E6/E7-positive murine cancer cells (TC-1). The HPV16 E7 open reading frame encodes functions analogous to these deleted adenovirus E1 proteins. In this study, an E1b-deleted CRAd (Adhz60) was evaluated for its ability to replicate and induce oncolysis in TC-1 cells. Adhz60-mediated oncolysis was similar in TC-1 and HeLa cells. Productive viral replication was evident based on expression of E1A and hexon, production of infectious virus progeny, and Adhz60-induced apoptosis. The results suggest that TC-1 murine cancer cells allow Adhz60 replication and oncolysis.


Assuntos
Adenoviridae/genética , Proteínas E1B de Adenovirus/genética , Apoptose/genética , Papillomavirus Humano 16/genética , Replicação Viral/genética , Animais , Apoptose/fisiologia , Linhagem Celular Tumoral , Células HEK293 , Células HeLa , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Proteínas Oncogênicas Virais/genética , Proteínas E7 de Papillomavirus/genética , Proteínas Repressoras/genética
14.
Med Mycol ; 56(4): 434-441, 2018 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-28992352

RESUMO

Trichosporon asahii is an opportunistic yeastlike fungus that colonizes the gastrointestinal and respiratory tracts and human skin. Although it is an important cause of disseminated infections by non-Candida species, there are a few reports related to its virulence factors and their possible role in in vivo pathogenicity. We developed a murine model of disseminated trichosporonosis in immunocompetent mice for the evaluation of the in vivo pathogenicity of 6 T. asahii isolates with different in vitro virulence factor profiles. Tissue fungal burden was determined on days 1, 3, 7, 15, and 25 post-challenge. Overall, the largest fungal load was detected in the kidney on the 5 experimental days, while brain, spleen, and liver displayed a comparatively low fungal count. We observed a fungal burden decrease in most experimental groups from day 15. Histological analysis showed the presence of T. asahii in tissue and a generalized inflammatory infiltrate of polymorphonuclear cells in the kidney, liver, red pulp of the spleen, and the hippocampus. Even though our isolates showed different in vitro virulence factors profiles, we did not detect relevant differences when assayed in vivo, except for a higher persistence of a protease- and biofilm-producing strain in kidney, liver, and brain.


Assuntos
Modelos Animais de Doenças , Trichosporon/enzimologia , Trichosporon/patogenicidade , Tricosporonose/microbiologia , Tricosporonose/patologia , Animais , Antifúngicos/uso terapêutico , Biofilmes/crescimento & desenvolvimento , Contagem de Colônia Microbiana , Humanos , Rim/microbiologia , Rim/patologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Trichosporon/crescimento & desenvolvimento , Trichosporon/isolamento & purificação , Tricosporonose/tratamento farmacológico , Virulência
15.
J BUON ; 23(3): 541-549, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30003717

RESUMO

Currently, nanomedicine is approaching the research of nanomaterials that could work as drug delivery systems, to increase the efficiency, specificity and safety of drugs reducing toxicity and side effects. In this regard, carbon nanotubes have acquired great interest due to their physicochemical properties. The use of platinum-based drugs is facing some troubles in the clinic due to their side effects such as nephrotoxicity, neutropenia, neurotoxicity, among others. In addition, cases of tumors resistant to these drugs have been recently observed. The goal of this review was to analyze the reports about the use of formulations of platinum-based drugs in carbon nanotubes, to know and establish the most functional and potential conditions for its use in cancer treatment, identifying perspectives and develop areas for the improvement of these nanomaterials in the application of cancer therapy.


Assuntos
Portadores de Fármacos/administração & dosagem , Sistemas de Liberação de Medicamentos/métodos , Nanomedicina/métodos , Nanotubos de Carbono , Compostos Organoplatínicos/administração & dosagem , Animais , Humanos
16.
Surg Radiol Anat ; 39(1): 29-38, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27177905

RESUMO

PURPOSE: The objective of this study was to characterize and compare the morphological characteristics of the dura mater, the pericranium, and the temporal fascia to ascertain the most adequate tissue to use as a dura graft. METHODS: 20 dura mater, 20 pericranium and 20 temporalis fascia samples were analyzed. Each of the samples was stained with hematoxylin and eosin, orcein, Van Gieson, Masson's trichrome and Verhoeff-Van Gieson (600 slides in total) for a general morphological evaluation, as well as a quantitative, morphometric and densitometric analysis of elastic fibers present in each of the tissues. RESULTS: The micro-densitometric analysis of the tissues indicated that the area occupied by the elastic fibers showed values of 1.766 ± 1.376, 4.580 ± 3.041, and 8.253 ± 4.467 % for the dura mater, the temporalis fascia and the pericranium, respectively (p < 0.05, all pairs). The values observed in the analysis of the density intensity were 3.42E+06 ± 2.57E+06, 1.41E+07 ± 1.28E+07, and 1.63E+07 ± 9.19E+06 for the dura mater, the temporalis fascia and the pericranium, respectively (p < 0.05), dura mater vs. temporalis fascia and dura mater vs. pericranium). CONCLUSIONS: This is the first study to compare the dura mater with tissues for dural autograft and to quantify the elastic component present in these tissues. The results indicate that the temporalis fascia is a better dural graft because of its intrinsic tissue properties.


Assuntos
Autoenxertos/transplante , Dura-Máter/cirurgia , Fáscia/transplante , Periósteo/transplante , Procedimentos de Cirurgia Plástica/métodos , Retalhos Cirúrgicos/transplante , Adulto , Idoso , Cadáver , Densitometria , Dura-Máter/transplante , Humanos , Masculino , Pessoa de Meia-Idade , Crânio/anatomia & histologia , Músculo Temporal/anatomia & histologia , Adulto Jovem
17.
Biotechnol Lett ; 37(4): 779-85, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25515795

RESUMO

Fusokines are proteins formed by the fusion of two cytokines. They have greater bioavailability and therapeutic potential than individual cytokines or a combination of different cytokines. Interferon-gamma-inducible protein 10 (CXCL10) and lymphotactin (XCL1) are members of the chemotactic family of cytokines, which induce tumor regression by eliciting immune-system cell chemotaxis. We engineered a replication-deficient adenoviral system expressing CXCL10/XCL1 fusokine (Ad FIL) and assessed its chemotactic response in vitro and in vivo. The CXCL10/XCL1 fusokine elicited a greater chemotactic effect in IL-2 stimulated lymphocytes than individual or combined cytokines in vitro. CXCL10/XCL1 fusokine biological activity was demonstrated in vivo by intratumoral chemoattraction of CXCR3+ cells. Thus, this novel CXCL10/XCL1 fusokine may represent a potential tool for gene therapy treatment of cancer and other illnesses that require triggering immune-system cell recruitment.


Assuntos
Quimiocina CXCL10/metabolismo , Quimiocinas C/metabolismo , Quimiotaxia , Vetores Genéticos , Linfócitos/fisiologia , Mastadenovirus/genética , Animais , Linhagem Celular , Quimiocina CXCL10/genética , Quimiocinas C/genética , Humanos , Linfócitos/efeitos dos fármacos , Camundongos Endogâmicos C57BL
18.
Biotechnol Lett ; 36(12): 2489-94, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25214209

RESUMO

Interleukin-22 (IL-22) participates in the modulation of innate immunity and inflammation. This cytokine has important therapeutic potential, such as with ulcerative colitis, liver and lung injury, and infection, in different animal models. We generated a Lactococcus lactis strain that secretes human IL-22 under the regulation of the nisin-inducible promoter. Identification and secretion of this cytokine was demonstrated using western blots of culture supernatants from IL-22-expressing bacteria. The recombinant IL-22 protein produced by L. lactis was biologically active as determined by its ability to induce IL-10 secretion when co-cultured with a colon epithelial cell line in vitro. We consider this novel strain a promising live vaccine for various therapeutic applications.


Assuntos
Interleucinas/metabolismo , Lactococcus lactis/metabolismo , Western Blotting , Linhagem Celular , Meios de Cultura/química , Células Epiteliais/efeitos dos fármacos , Expressão Gênica , Regulação Bacteriana da Expressão Gênica/efeitos dos fármacos , Humanos , Interleucinas/genética , Lactococcus lactis/genética , Nisina/metabolismo , Regiões Promotoras Genéticas , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Interleucina 22
19.
Mem Inst Oswaldo Cruz ; 109(6): 814-9, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25317710

RESUMO

The characteristics of tuberculosis (TB) patients related to a chain of recent TB transmissions were investigated. Mycobacterium tuberculosis (MTB) isolates (120) were genotyped using the restriction fragment length polymorphism-IS6110 (R), spacer oligotyping (S) and mycobacterial interspersed repetitive units-variable number of tandem repeats (M) methods. The MTB isolates were clustered and the clusters were grouped according to the similarities of their genotypes. Spearman's rank correlation coefficients between the groups of MTB isolates with similar genotypes and those patient characteristics indicating a risk for a pulmonary TB (PTB) chain transmission were ana- lysed. The isolates showing similar genotypes were distributed as follows: SMR (5%), SM (12.5%), SR (1.67%), MR (0%), S (46.67%), M (5%) and R (0%). The remaining 35 cases were orphans. SMR exhibited a significant correlation (p < 0.05) with visits to clinics, municipalities and comorbidities (primarily diabetes mellitus). S correlated with drug consumption and M with comorbidities. SMR is needed to identify a social network in metropolitan areas for PTB transmission and S and M are able to detect risk factors as secondary components of a transmission chain of TB.


Assuntos
Técnicas de Genotipagem/métodos , Mycobacterium tuberculosis/genética , Tuberculose Pulmonar/microbiologia , Tuberculose Pulmonar/transmissão , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Cidades , Comorbidade , DNA Bacteriano/isolamento & purificação , Feminino , Genótipo , Humanos , Sequências Repetitivas Dispersas/genética , Masculino , México/epidemiologia , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Epidemiologia Molecular/métodos , Mycobacterium tuberculosis/classificação , Mycobacterium tuberculosis/isolamento & purificação , Polimorfismo de Fragmento de Restrição/genética , Fatores de Risco , Fatores Sociológicos , Estatísticas não Paramétricas , Sequências de Repetição em Tandem/genética , Tuberculose Pulmonar/epidemiologia , Tuberculose Pulmonar/genética , População Urbana , Adulto Jovem
20.
Biochem Biophys Rep ; 39: 101770, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39055170

RESUMO

Entamoeba histolytica is a protozoan parasite that belongs to the Amoebozoa supergroup whose study related to the nucleocytoplasmic transport of proteins through the nucleus is poorly studied. In this work, we have performed in silico predictions of the potential nuclear localization signals (NLS) corresponding to the proteome of 8201 proteins from Entamoeba histolytica annotated in the AmoebaDB database. We have found the presence of monopartite nuclear localization signals (MNLSs), bipartite nuclear localization signals (BNLSs), and non-canonical monopartite NLSs with lengths exceeding 20 amino acid residues. Additionally, we detected a new type of NLS consisting of multiple juxtaposed bipartite NLSs (JNLSs) that have not been described in any eukaryotic organism. Also, we have generated consensus sequences for the nuclear import of proteins with the NLSs obtained. Docking experiments between EhImportin α and an MNLS, BNLS, and JNLS outlined the interacting residues between the Importin and cargo proteins, emphasizing their putative roles in nuclear import. By transfecting HA-tagged protein constructs, we assessed the nuclear localization of MNLS (U1A and U2AF1), JMNLS (U2AF2), and non-canonical NLS (N-terminus of Pol ll) in vivo. Our data provide the basis for understanding the nuclear transport process in E. histolytica.

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