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1.
Drug Dev Res ; 85(2): e22175, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38567708

RESUMO

Icaritin is a natural prenylated flavonoid derived from the Chinese herb Epimedium. The compound has shown antitumor effects in various cancers, especially hepatocellular carcinoma (HCC). Icaritin exerts its anticancer activity by modulating multiple signaling pathways, such as IL-6/JAK/STAT3, ER-α36, and NF-κB, affecting the tumor microenvironment and immune system. Several clinical trials have evaluated the safety and efficacy of icaritin in advanced HCC patients with poor prognoses, who are unsuitable for conventional therapies. The results have demonstrated that icaritin can improve survival, delay progression, and produce clinical benefits in these patients, with a favorable safety profile and minimal adverse events. Moreover, icaritin can enhance the antitumor immune response by regulating the function and phenotype of various immune cells, such as CD8+ T cells, MDSCs, neutrophils, and macrophages. These findings suggest that icaritin is a promising candidate for immunotherapy in HCC and other cancers. However, further studies are needed to elucidate the molecular mechanisms and optimal dosing regimens of icaritin and its potential synergistic effects with other agents. Therefore, this comprehensive review of the scientific literature aims to summarize advances in the knowledge of icaritin in preclinical and clinical studies as well as the pharmacokinetic, metabolism, toxicity, and mechanisms action to recognize the main challenge, gaps, and opportunities to develop a medication that cancer patients can use. Thus, our main objective was to clarify the current state of icaritin for use as an anticancer drug.


Assuntos
Antineoplásicos , Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Flavonoides/farmacologia , Flavonoides/uso terapêutico , Linhagem Celular Tumoral , Microambiente Tumoral
2.
Cancer Cell Int ; 23(1): 180, 2023 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-37633886

RESUMO

Dietary compounds in cancer prevention have gained significant consideration as a viable method. Indole-3-carbinol (I3C) and 3,3'-diindolylmethane (DIM) are heterocyclic and bioactive chemicals found in cruciferous vegetables like broccoli, cauliflower, cabbage, and brussels sprouts. They are synthesized after glycolysis from the glucosinolate structure. Clinical and preclinical trials have evaluated the pharmacokinetic/pharmacodynamic, effectiveness, antioxidant, cancer-preventing (cervical dysplasia, prostate cancer, breast cancer), and anti-tumor activities of I3C and DIM involved with polyphenolic derivatives created in the digestion showing promising results. However, the exact mechanism by which they exert anti-cancer and apoptosis-inducing properties has yet to be entirely understood. Via this study, we update the existing knowledge of the state of anti-cancer investigation concerning I3C and DIM chemicals. We have also summarized; (i) the recent advancements in the use of I3C/DIM as therapeutic molecules since they represent potentially appealing anti-cancer agents, (ii) the available literature on the I3C and DIM characterization, and the challenges related to pharmacologic properties such as low solubility, and poor bioavailability, (iii) the synthesis and semi-synthetic derivatives, (iv) the mechanism of anti-tumor action in vitro/in vivo, (v) the action in cellular signaling pathways related to the regulation of apoptosis and anoikis as well as the cell cycle progression and cell proliferation such as peroxisome proliferator-activated receptor and PPARγ agonists; SR13668, Akt inhibitor, cyclins regulation, ER-dependent-independent pathways, and their current medical applications, to recognize research opportunities to potentially use these compounds instead chemotherapeutic synthetic drugs.

3.
Rev Neurosci ; 34(8): 915-932, 2023 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-37409540

RESUMO

The transsulfuration pathway (TSP) is a metabolic pathway involving sulfur transfer from homocysteine to cysteine. Transsulfuration pathway leads to many sulfur metabolites, principally glutathione, H2S, taurine, and cysteine. Key enzymes of the TSP, such as cystathionine ß-synthase and cystathionine γ-lyase, are essential regulators at multiple levels in this pathway. TSP metabolites are implicated in many physiological processes in the central nervous system and other tissues. TSP is important in controlling sulfur balance and optimal cellular functions such as glutathione synthesis. Alterations in the TSP and related pathways (transmethylation and remethylation) are altered in several neurodegenerative diseases, including Parkinson's disease, suggesting their participation in the pathophysiology and progression of these diseases. In Parkinson's disease many cellular processes are comprised mainly those that regulate redox homeostasis, inflammation, reticulum endoplasmic stress, mitochondrial function, oxidative stress, and sulfur content metabolites of TSP are involved in these damage processes. Current research on the transsulfuration pathway in Parkinson's disease has primarily focused on the synthesis and function of certain metabolites, particularly glutathione. However, our understanding of the regulation of other metabolites of the transsulfuration pathway, as well as their relationships with other metabolites, and their synthesis regulation in Parkinson´s disease remain limited. Thus, this paper highlights the importance of studying the molecular dynamics in different metabolites and enzymes that affect the transsulfuration in Parkinson's disease.


Assuntos
Cisteína , Doença de Parkinson , Humanos , Cisteína/metabolismo , Enxofre/metabolismo , Cistationina beta-Sintase/metabolismo , Glutationa/metabolismo
4.
Biochem Biophys Rep ; 35: 101492, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37304131

RESUMO

Cancer treatment typically involves multiple strategies, such as surgery, radiotherapy, and chemotherapy, to remove tumors. However, chemotherapy often causes side effects, and there is a constant search for new drugs to alleviate them. Natural compounds are a promising alternative to this problem. Indole-3-carbinol (I3C) is a natural antioxidant agent that has been studied as a potential cancer treatment. I3C is an agonist of the aryl hydrocarbon receptor (AhR), a transcription factor that plays a role in the expression of genes related to development, immunity, circadian rhythm, and cancer. In this study, we investigated the effect of I3C on cell viability, migration, invasion properties, as well as mitochondrial integrity in hepatoma, breast, and cervical cancer cell lines. We found that all tested cell lines showed impaired carcinogenic properties and alterations in mitochondrial membrane potential after treatment with I3C. These results support the potential use of I3C as a supplementary treatment for various types of cancer.

5.
Cell Mol Biol (Noisy-le-grand) ; 69(3): 52-63, 2023 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-37300689

RESUMO

Dysmenorrhea is the combination of cramps and pain associated with the menstrual period, and the symptoms affect at least 30% of women worldwide. Tolerance to symptoms depends on each person's pain threshold; however, dysmenorrhea seriously affects daily activities and chronically reduces the quality of life. Some dysmenorrhea cases even require hospitalization due to unbearable symptoms of severe pain. Dysmenorrhea is an underestimated affectation and remains even in different first-world countries as a taboo subject, promoted by the establishment of an apparent policy of gender equality. A person with primary or secondary dysmenorrhea requires medical assistance in choosing the best treatment and an integral approach. This review intends to demonstrate the impact of dysmenorrhea on quality of life. We describe the pathophysiology of this disorder from a molecular point of view and perform a comprehensive compilation and analysis of the most critical findings in the therapeutic management of dysmenorrhea. Likewise, we propose an interdisciplinary approach to the phenomenon of dysmenorrhea at the cellular level in a concise way and the botanical, pharmacological, and medical applications for its management. Since dysmenorrhea symptoms can vary between individuals, medical treatment cannot be generalized and depends on each patient. Therefore, we hypothesized that a suitable strategy could result from the combination of pharmacological therapy aided by a non-pharmacological approach.


Assuntos
Dismenorreia , Qualidade de Vida , Feminino , Humanos , Dismenorreia/tratamento farmacológico , Medição da Dor
6.
Front Cell Neurosci ; 17: 1125109, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36998270

RESUMO

Diverse neurological symptoms have been reported in patients with SARS-CoV-2 disease (COVID-19), including stroke, ataxia, meningitis, encephalitis, and cognitive impairment. These alterations can cause serious sequelae or death and are associated with the entry of SARS-CoV-2 into the Central Nervous System (CNS). This mini-review discusses the main proposed mechanisms by which SARS-CoV-2 interacts with the blood-brain barrier (BBB) and its involvement in the passage of drugs into the CNS. We performed a search in PubMed with the terms "COVID-19" or "SARS-CoV-2" and "blood-brain barrier injury" or "brain injury" from the year 2019 to 2022. We found proposed evidence that SARS-CoV-2 infects neurovascular cells and increases BBB permeability by increasing the expression of matrix metalloproteinase-9 that degrades type IV collagen in the basement membrane and through activating RhoA, which induces restructuring of the cytoskeleton and alters the integrity of the barrier. The breakdown of the BBB triggers a severe inflammatory response, causing the cytokine storm (release of IL-1ß, IL-6, TNF-α, etc.) characteristic of the severe phase of COVID-19, which includes the recruitment of macrophages and lymphocytes and the activation of astrocytes and microglia. We conclude that the increased permeability of the BBB would allow the passage of drugs that would not reach the brain in a normal physiological state, thus enhancing certain drugs' beneficial or adverse effects. We hope this article will encourage research on the impact of drugs on patients with COVID-19 and recovered patients with sequelae, focusing mainly on possible dose adjustments and changes in pharmacokinetic parameters.

7.
Life (Basel) ; 13(2)2023 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-36836894

RESUMO

Lithium is a therapeutic cation used to treat bipolar disorders but also has some important features as an anti-cancer agent. In this review, we provide a general overview of lithium, from its transport into cells, to its innovative administration forms, and based on genomic, transcriptomic, and proteomic data. Lithium formulations such as lithium acetoacetate (LiAcAc), lithium chloride (LiCl), lithium citrate (Li3C6H5O7), and lithium carbonate (Li2CO3) induce apoptosis, autophagy, and inhibition of tumor growth and also participate in the regulation of tumor proliferation, tumor invasion, and metastasis and cell cycle arrest. Moreover, lithium is synergistic with standard cancer therapies, enhancing their anti-tumor effects. In addition, lithium has a neuroprotective role in cancer patients, by improving their quality of life. Interestingly, nano-sized lithium enhances its anti-tumor activities and protects vital organs from the damage caused by lipid peroxidation during tumor development. However, these potential therapeutic activities of lithium depend on various factors, such as the nature and aggressiveness of the tumor, the type of lithium salt, and its form of administration and dosage. Since lithium has been used to treat bipolar disorder, the current study provides an overview of its role in medicine and how this has changed. This review also highlights the importance of this repurposed drug, which appears to have therapeutic cancer potential, and underlines its molecular mechanisms.

8.
Curr Issues Mol Biol ; 44(5): 2054-2068, 2022 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-35678668

RESUMO

Cervical cancer (CC) is one of the most common cancers in women, and is linked to human papillomavirus (HPV) infection. The virus oncoprotein E6 binds to p53, resulting in its degradation and allowing uncontrolled cell proliferation. Meanwhile, the HPV E7 protein maintains host cell differentiation by targeting retinoblastoma tumor suppressor. The host cell can ubiquitinate E6 and E7 through UBE2L3, whose expression depends on the interaction between the aryl hydrocarbon receptor (AhR) with Xenobiotic Responsive Elements (XREs) located in the UBE2L3 gene promoter. In this study, we used cell culture to determine the effect of indole-3-carbinol (I3C) over cellular viability, apoptosis, cell proliferation, and mRNA levels of UBE2L3 and CYP1A1. In addition, patients' samples were used to determine the mRNA levels of UBE2L3 and CYP1A1 genes. We found that I3C promotes the activation of AhR and decreases cell proliferation, possibly through UBE2L3 mRNA induction, which would result in the ubiquitination of HPV E7. Since there is a strong requirement for selective and cost-effective cancer treatments, natural AhR ligands such as I3C could represent a novel strategy for cancer treatment.

9.
Ann Surg Oncol ; 2022 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-35320428

RESUMO

BACKGROUND: The expression of liver kinase B1 (LKB-1) has been associated with prognosis in squamous cell carcinoma of the oral cavity (SCCOC). This study aimed to define the prognostic role of LKB-1 expression for patients with SCCOC and the suitability of its integration into a multivariate prognostic model. METHODS: A retrospective cohort study of patients with SCCOC was conducted in a cancer center. Expression of LKB-1 was evaluated by immunohistochemistry, and multivariate analysis defined prognostic factors associated with recurrence, recurrence-free survival (RFS), and overall survival (OS). The logistic regression model was used to construct a predictive computer software program. RESULTS: Of the 201 patients in this study, 104 (51.7%) experienced recurrence of their disease. Lower expression of LKB-1, high-risk histopathology, and advanced tumor-node-metastasis (TNM) stages were independent factors via multivariate analysis associated with the increased recurrence risk, poor RFS, and poor OS. If lack of LKB-1 expression is considered the reference category, the factors independently associated with recurrence were low (odds ratio [OR], 0.157; 95% confidence interval [CI], 0.044-0.557), intermediate (OR, 0.073; 95% CI, 0.017-0.319), and intense (OR, 0.047; 95% CI, 0.007-0.304) expression of LKB-1. This model permitted construction of a computer software program capable of prediction with receiver operating characteristic analysis (area under the curve, 0.925) and led to the definition of five prognostic groups with a biologic gradient. CONCLUSION: These results suggest that LKB-1 expression in patients with SCCOC is of robust prognostic value and complements the TNM staging system. The proposed model requires external validation in prospective observational studies.

11.
Cancer Cell Int ; 21(1): 649, 2021 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-34863151

RESUMO

BACKGROUND: The ESR1 gene suffers methylation changes in many types of cancers, including breast cancer (BC), the most frequently diagnosed cancer in women that is also present in men. Methylation at promoter A of ESR1 is the worse prognosis in terms of overall survival; thus, the early detection, prognostic, and prediction of therapy involve some methylation biomarkers. METHODS: Therefore, our study aimed to examine the methylation levels at the ESR1 gene in samples from Mexican BC patients and its possible association with menopausal status. RESULTS: We identified a novel 151-bp CpG island in the promoter A of the ESR1 gene. Interestingly, methylation levels at this CpG island in positive ERα tumors were approximately 50% less than negative ERα or control samples. Furthermore, methylation levels at ESR1 were associated with menopausal status. In postmenopausal patients, the methylation levels were 1.5-fold higher than in premenopausal patients. Finally, according to tumor malignancy, triple-negative cancer subtypes had higher ESR1 methylation levels than luminal/HER2+ or luminal A subtypes. CONCLUSIONS: Our findings suggest that methylation at this novel CpG island might be a promising prognosis marker.

12.
Cell Mol Biol (Noisy-le-grand) ; 67(1): 101-105, 2021 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-34817361

RESUMO

Parkinson's disease (PD) is one of the most prevalent neurodegenerative disorders worldwide. It is caused by the degeneration of dopaminergic neurons from the substantia nigra pars compacta. This neuronal loss causes the dopamine deficiency that leads to a series of functional changes within the basal ganglia, producing motor control abnormalities. L-DOPA is considered the gold standard for PD treatment, and it may alleviate its clinical manifestations for some time. However, its prolonged administration produces tolerance and several severe side effects, including dyskinesias and gastrointestinal disorders. Thus, there is an urgent need to find effective medications, and current trends have proposed some natural products as emerging options for this purpose. Concerning this, curcumin represents a promising bioactive compound with high therapeutic potential. Diverse studies in cellular and animal models have suggested that curcumin could be employed for the treatment of PD. Therefore, the objective of this narrative mini-review is to present an overview of the possible therapeutic effects of curcumin and the subjacent molecular mechanisms. Moreover, we describe several possible nanocarrier-based approaches to improve the bioavailability of curcumin and enhance its biological activity.


Assuntos
Encéfalo/efeitos dos fármacos , Curcumina/administração & dosagem , Nanopartículas/administração & dosagem , Doença de Parkinson/tratamento farmacológico , Animais , Disponibilidade Biológica , Encéfalo/metabolismo , Curcumina/química , Curcumina/farmacocinética , Liberação Controlada de Fármacos , Glutationa Peroxidase/metabolismo , Humanos , NADPH Oxidases/antagonistas & inibidores , NADPH Oxidases/metabolismo , Nanopartículas/química , Fármacos Neuroprotetores/administração & dosagem , Fármacos Neuroprotetores/química , Fármacos Neuroprotetores/farmacocinética , Doença de Parkinson/metabolismo , Espécies Reativas de Oxigênio/antagonistas & inibidores , Espécies Reativas de Oxigênio/metabolismo , Superóxido Dismutase/metabolismo , Resultado do Tratamento , Regulação para Cima/efeitos dos fármacos
13.
Cell Mol Biol (Noisy-le-grand) ; 67(1): 96-100, 2021 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-34817362

RESUMO

The skin is the largest organ in the human body, and due to its barrier function, it is susceptible to multiple injuries. The appearance of infections during the wound healing process is a complication that represents a formidable hospital challenge. The presence of opportunistic bacteria with sophisticated resistance mechanisms is difficult to eradicate and compromises patients' lives. Therefore, the search for new efficacious treatments from natural sources that prevent and counteract infections, in addition to promoting the healing process, has increased in recent years. In this respect, films with the capability to protect wounds and release drugs are the presentation that predominates commercially in the hospital environment. Those films can offer several mechanical advantages such as physical protection to prevent opportunistic bacteria's entry, regulation of gas exchange, and capture of exudate through a swelling process. Wound dressings are generally curative materials easily adaptable to different anatomical regions, with high strength and elasticity, and some are even bioabsorbable. Additionally, the components of the films can actively participate in promoting the healing process. Even more, the film can be made up of carriers with other active participants to prevent and eradicate infections. Therefore, the extensive versatility, practicality, and usefulness of films from natural sources to address infectious processes during wound healing are relevant and recurrent themes. This work presents an analysis of the state-of-the-art of films with natural products focused on preventing and eradicating infections in wound healing.


Assuntos
Produtos Biológicos/farmacologia , Infecções Oportunistas/prevenção & controle , Cicatrização/efeitos dos fármacos , Infecção dos Ferimentos/prevenção & controle , Ferimentos e Lesões/prevenção & controle , Produtos Biológicos/química , Humanos , Hidrogéis/química , Hidrogéis/farmacologia , Membranas Artificiais , Infecções Oportunistas/microbiologia , Plastificantes/química , Plastificantes/farmacologia , Substâncias Protetoras/química , Substâncias Protetoras/farmacologia , Infecção dos Ferimentos/microbiologia , Ferimentos e Lesões/microbiologia
14.
Cell Mol Biol (Noisy-le-grand) ; 67(1): 89-95, 2021 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-34817363

RESUMO

Periodontal pain is a public health problem derived from different conditions, including periodontal diseases, prosthetic complications, and even extractions performed by dentist. There are various treatments to control acute dental pain, being the administration of analgesics, such as Lysine Clonixinate (LC), a common practice. Unfortunately, higher and repeated dosages are usually required. The purpose of this work was to develop a prolonged release pharmaceutical form as an alternative treatment for dental pain. Hence, we conceived a film based on guar gum and loaded different concentrations of LC. We evaluated the film's appearance, brittleness, strength, and flexibility, and then chose one formulation for adequate characteristics. Subsequently, we assessed the morphology, thermal behavior, and swelling properties of the films (LC-free and -loaded). Finally, we performed the release studies of LC from the films in vitro using a simulated saliva medium and employed several mathematical models to evaluate the release kinetics. Guar gum is a natural polymer obtained from the endosperm of Cyamopsis tetragonolobus that presents properties such as biosafety, biocompatibility, and biodegradability. Thus, it represents a potential excipient for use in pharmaceutical formulations. Moreover, our results revealed that the LC-loaded film presented a high adherence, suitable swelling behavior, high LC content, and a prolonged drug release. Therefore, the LC-loaded film may be considered a potential option to be applied as an alternative to treat dental pain.


Assuntos
Clonixina/análogos & derivados , Lisina/análogos & derivados , Dor/tratamento farmacológico , Doenças Periodontais/tratamento farmacológico , Polissacarídeos Bacterianos/química , Analgésicos/farmacocinética , Analgésicos/uso terapêutico , Clonixina/farmacocinética , Clonixina/uso terapêutico , Liberação Controlada de Fármacos , Excipientes/química , Humanos , Cinética , Lisina/farmacocinética , Lisina/uso terapêutico , Membranas Artificiais , Microscopia Eletrônica de Varredura , Dor/complicações , Doenças Periodontais/complicações , Polímeros/química , Polissacarídeos Bacterianos/ultraestrutura , Temperatura , Termogravimetria/métodos
15.
Cell Mol Biol (Noisy-le-grand) ; 67(1): 80-88, 2021 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-34817364

RESUMO

Bacterial vaginosis is a vaginal infection that affects 60% of women of reproductive age worldwide. It is mainly caused by the bacterium Gardnerella vaginalis and is a factor that increases the probability of getting sexually transmitted diseases. We aimed to develop a new pharmaceutical form for the treatment of vaginal infections. We employed the solving-casting method to fabricate a polymeric film with Xanthan gum, a natural polymer produced by the bacterium Xanthomonas campestris, and metronidazole, one of the most commonly used drugs for vaginal infections. In order to characterize the film, we measured pH, dose uniformity, dissolution profile, and the percentage of swelling. Moreover, we performed a thermogravimetric analysis and scanning electron microscopy. The results demonstrated a pH suitable for vaginal application and uniform distribution of the drug in the film. Also, the formulation exhibited a high percentage of swelling and a slow release of the drug in a simulated vaginal fluid medium. All these attributes indicated that the manufactured film has ideal characteristics to be used and administered vaginally. It could be an excellent alternative to treat bacterial vaginosis and also improve user adherence.


Assuntos
Gardnerella vaginalis/efeitos dos fármacos , Metronidazol/uso terapêutico , Polissacarídeos Bacterianos/química , Vagina/efeitos dos fármacos , Vaginose Bacteriana/tratamento farmacológico , Antibacterianos/administração & dosagem , Antibacterianos/farmacocinética , Antibacterianos/uso terapêutico , Liberação Controlada de Fármacos , Feminino , Gardnerella vaginalis/fisiologia , Humanos , Concentração de Íons de Hidrogênio , Membranas Artificiais , Metronidazol/administração & dosagem , Metronidazol/farmacocinética , Microscopia Eletrônica de Varredura , Polímeros/química , Polissacarídeos Bacterianos/ultraestrutura , Temperatura , Termogravimetria/métodos , Resultado do Tratamento , Vagina/microbiologia , Vaginose Bacteriana/microbiologia
16.
Cell Mol Biol (Noisy-le-grand) ; 67(1): 73-79, 2021 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-34817365

RESUMO

Xanthan gum (XG) and polyvinylpyrrolidone (PVP) are two polymers with low toxicity, high biocompatibility, biodegradability, and high hydrophilicity, making them promising candidates for multiple medical aspects. The present work aimed to synthesize a hydrogel from a mixture of XG and PVP and crosslinked by gamma irradiation. We assessed the hydrogel through a series of physicochemical (FT-IR, TGA, SEM, and percentage of swelling) and biological (stability of the hydrogel in cell culture medium) methods that allowed to determine its applicability. The structural evaluation by infrared spectrum demonstrated that a crosslinked hydrogel was obtained from the combination of polymers. The calorimetric test and swelling percentage confirmed the formation of the bonds responsible for the crosslinked structure. The calorimetric test evidenced that the hydrogel was resistant to decomposition in contrast to non- irradiated material. The determination of the swelling degree showed constant behavior over time, indicating a structure resistant to hydrolysis. This phenomenon also occurred during the test of stability in a cell culture medium. Additionally, microscopic analysis of the sample revealed an amorphous matrix with the presence of porosity. Thus, the findings reveal the synthesis of a novel material that has desirable attributes for its potential application in pharmaceutical and biomedical areas.


Assuntos
Raios gama , Hidrogéis/efeitos da radiação , Polímeros/efeitos da radiação , Polissacarídeos Bacterianos/efeitos da radiação , Povidona/efeitos da radiação , Hidrogéis/síntese química , Hidrogéis/química , Microscopia Eletrônica de Varredura , Modelos Químicos , Estrutura Molecular , Polímeros/síntese química , Polímeros/química , Polissacarídeos Bacterianos/síntese química , Polissacarídeos Bacterianos/química , Porosidade , Povidona/síntese química , Povidona/química , Espectroscopia de Infravermelho com Transformada de Fourier/métodos , Temperatura , Termogravimetria/métodos
17.
Cell Mol Biol (Noisy-le-grand) ; 67(1): 64-72, 2021 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-34817366

RESUMO

The purpose of our study was to obtain new wound dressings in the form of hydrogels that promote wound healing taking advantage of the broad activities of elastin (ELT) in physiological processes. The hydrogel of ELT and polyvinylpyrrolidone (PVP; ELT-PVP) was obtained by cross-linking induced by gamma irradiation at a dose of 25 kGy. The physicochemical changes attributed to cross-linking were analyzed through scanning electron microscopy (SEM), infrared spectroscopy analysis with Fourier transform (FTIR), differential scanning calorimetry (DSC), and thermogravimetric analysis (TGA). Furthermore, we performed a rheological study to determine the possible changes in the fluidic macroscopic properties produced by the cross-linking method. Finally, we accomplished viability and proliferation analyses of human dermal fibroblasts in the presence of the hydrogel to evaluate its biological characteristics. The hydrogel exhibited a porous morphology, showing interconnected porous with an average pore size of 16 ± 8.42 µm. The analysis of FTIR, DSC, and TGA revealed changes in the chemical structure of the ELT-PVP hydrogel after the irradiation process. Also, the hydrogel exhibited a rheological behavior of a pseudoplastic and thixotropic fluid. The hydrogel was biocompatible, demonstrating high cell viability, whereas ELT presented low biocompatibility at high concentrations. In summary, the hydrogel obtained by gamma irradiation revealed the appropriate morphology to be applied as a wound dressing. Interestingly, the hydrogel exhibited a higher percentage of cell viability compared with ELT, suggesting that the cross-linking of ELT with PVP is a suitable strategy for biological applications of ELT without generating cellular damage.


Assuntos
Materiais Biocompatíveis/metabolismo , Elastina/metabolismo , Curativos Oclusivos , Polimerização/efeitos da radiação , Povidona/metabolismo , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Varredura Diferencial de Calorimetria/métodos , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Elastina/química , Elastina/ultraestrutura , Fibroblastos/citologia , Fibroblastos/efeitos dos fármacos , Humanos , Hidrogéis/química , Hidrogéis/metabolismo , Hidrogéis/farmacologia , Microscopia Eletrônica de Varredura , Povidona/química , Povidona/farmacologia , Espectroscopia de Infravermelho com Transformada de Fourier/métodos , Termogravimetria/métodos , Cicatrização/efeitos dos fármacos
18.
Cell Mol Biol (Noisy-le-grand) ; 67(1): 58-63, 2021 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-34817367

RESUMO

Hyaluronic acid (HA) is one of the most attractive natural polymers employed in biomaterials with biological applications. This polysaccharide is found in different tissues of the body because it is a natural component of the extracellular matrix; furthermore, it has crucial functions in cell growth, migration, and differentiation. Since its biological characteristics, HA has been utilized for the new biomaterial's development for tissue engineering, such as hydrogels. These hydrophilic macromolecular networks have gained significant attention due to their unique properties, making them potential candidates to be applied in biomedical fields. Different mechanisms to obtain hydrogels have been described. However, the research of new non-toxic methods has been growing in recent years. In this study, we prepared a new hydrogel of HA and polyvinyl alcohol by the cost-effective technique of cross-linking by gamma irradiation. The hydrogel was elaborated for the first time and was characterized by several methods such as Fourier Transform Infrared Spectroscopy, Differential Scanning Calorimetry, Thermogravimetric Analysis, and Scanning Electron Microscopy. Likewise, we evaluated the cytotoxicity of the biomaterial and its influence on cell migration in human fibroblasts. Furthermore, we provide preliminary evidence of the wound closure effect in a cellular wound model. The novel hydrogel offers an increase of HA stability with the potential to expand the useful life of HA in its different medical applications.


Assuntos
Materiais Biocompatíveis/efeitos da radiação , Raios gama , Ácido Hialurônico/efeitos da radiação , Polímeros/efeitos da radiação , Álcool de Polivinil/efeitos da radiação , Materiais Biocompatíveis/síntese química , Materiais Biocompatíveis/farmacologia , Movimento Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Fibroblastos/citologia , Fibroblastos/efeitos dos fármacos , Humanos , Ácido Hialurônico/síntese química , Ácido Hialurônico/ultraestrutura , Microscopia Eletrônica de Varredura , Modelos Químicos , Estrutura Molecular , Polímeros/síntese química , Polímeros/farmacologia , Álcool de Polivinil/síntese química , Álcool de Polivinil/farmacologia , Espectroscopia de Infravermelho com Transformada de Fourier/métodos , Engenharia Tecidual/métodos
19.
Molecules ; 26(7)2021 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-33916823

RESUMO

Nanoparticles possess a huge potential to be employed in numerous biomedical purposes; their applications may include drug delivery systems, gene therapy, and tissue engineering. However, the in vivo use in biomedical applications requires that nanoparticles exhibit sterility. Thus, diverse sterilization techniques have been developed to remove or destroy microbial contamination. The main sterilization methods include sterile filtration, autoclaving, ionizing radiation, and nonionizing radiation. Nonetheless, the sterilization processes can alter the stability, zeta potential, average particle size, and polydispersity index of diverse types of nanoparticles, depending on their composition. Thus, these methods may produce unwanted effects on the nanoparticles' characteristics, affecting their safety and efficacy. Moreover, each sterilization method possesses advantages and drawbacks; thus, the suitable method's choice depends on diverse factors such as the formulation's characteristics, batch volume, available methods, and desired application. In this article, we describe the current sterilization methods of nanoparticles. Moreover, we discuss the advantages and drawbacks of these methods, pointing out the changes in nanoparticles' biological and physicochemical characteristics after sterilization. Our main objective was to offer a comprehensive overview of terminal sterilization processes of nanoparticles for biomedical applications.


Assuntos
Tecnologia Biomédica , Nanopartículas/química , Esterilização , Filtração , Radiação Ionizante
20.
J Cancer Res Ther ; 16(6): 1279-1286, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33342785

RESUMO

CONTEXT: Four single-nucleotide polymorphisms (SNPs) in Mexican patients and their association with the development of breast cancer (BC). AIMS: This work is focused on determining the association of fibroblast growth factor receptor (rs12196489), TOX3 (rs3803662), human telomerase reverse transcriptase (h TERT, rs10069690), and FTO (rs17817449) polymorphisms and BC in a cohort of Mexican women. SETTINGS AND DESIGN: The study included 56 patients with a confirmed diagnosis of BC and 83 controls. Clinical characteristics were obtained from medical records. SUBJECTS AND METHODS: Genomic DNA from the samples was obtained from lymphocytes, and the genotyping of rs12196489, rs3803662, rs10069690, and rs17817449 polymorphisms was performed by real-time polymerase chain reaction using specific TaqMan probes. Statistical analysis was assessed to evaluate the distribution of genotype frequencies between cases and controls. STATISTICAL ANALYSIS: We used the STATA Statistical Package (version 10.1; STATA Corp., College Station, TX, USA). Student's t-test, χ2 test, or Fisher's exact test was used to evaluate the distribution of genotype frequencies. RESULTS: No statistical differences in allelic and genotypic frequencies were found between patients with BC and controls for SNPs: rs1219648, rs3803662, and rs17817449. Interestingly, according to the χ2 test, a significant difference was exhibited for rs10069690 (odds ratio = 0.095; 95% confidence interval = 0.038-0.214; P < 0.001). CONCLUSIONS: The h TERT (rs10069690) polymorphism might be associated with BC in Mexican women. Nevertheless, additional studies in a larger cohort are required to confirm this association and to possibly use this polymorphism as a potential biomarker in the early diagnosis of BC.


Assuntos
Biomarcadores Tumorais/genética , Neoplasias da Mama/genética , Adulto , Dioxigenase FTO Dependente de alfa-Cetoglutarato/genética , Proteínas Reguladoras de Apoptose/genética , Biomarcadores Tumorais/sangue , Neoplasias da Mama/sangue , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/patologia , Estudos de Casos e Controles , Estudos de Coortes , Feminino , Predisposição Genética para Doença , Genótipo , Humanos , México/epidemiologia , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Receptor Tipo 2 de Fator de Crescimento de Fibroblastos/genética , Telomerase/genética , Transativadores/genética
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