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1.
Eur J Neurosci ; 59(7): 1441-1459, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38151481

RESUMEN

Dopamine D2 receptor (D2R) is expressed in striatopallidal neurons and decreases forskolin-stimulated cyclic adenine monophosphate (cAMP) accumulation and gamma-aminobutyric acid (GABA) release. Dopamine D3 receptor (D3R) mRNA is expressed in a population of striatal D2R-expressing neurons. Also, D3R protein and binding have been reported in the neuropil of globus pallidus. We explore whether D2R and D3R colocalize in striatopallidal terminals and whether D3R modulates the D2R effect on forskolin-stimulated [3H]cAMP accumulation in pallidal synaptosomes and high K+ stimulated-[3H]GABA release in pallidal slices. Previous reports in heterologous systems indicate that calmodulin (CaM) and CaMKII modulate D2R and D3R functions; thus, we study whether this system regulates its functional interaction. D2R immunoprecipitates with CaM, and pretreatment with ophiobolin A or depolarization of synaptosomes with 15 mM of K+ decreases it. Both treatments increase the D2R inhibition of forskolin-stimulated [3H]cAMP accumulation when activated with quinpirole, indicating a negative modulation of CaM on D2R function. Quinpirole also activates D3R, potentiating D2R inhibition of cAMP accumulation in the ophiobolin A-treated synaptosomes. D2R and D3R immunoprecipitate in pallidal synaptosomes and decrease after the kainic acid striatal lesion, indicating the striatal origin of the presynaptic receptors. CaM-kinase II alfa (CaMKIIα) immunoprecipitates with D3R and increases after high K+ depolarization. In the presence of KN62, a CaMKIIα blocker, D3R potentiates D2R effects on cAMP accumulation in depolarized synaptosomes and GABA release in pallidal slices, indicating D3R function regulation by CaMKIIα. Our data indicate that D3R potentiates the D2R effect on cAMP accumulation and GABA release at pallidal terminals, an interaction regulated by the CaM-CaMKIIα system.


Asunto(s)
Calmodulina , Receptores de Dopamina D3 , Sesterterpenos , Receptores de Dopamina D3/metabolismo , Quinpirol/farmacología , Calmodulina/metabolismo , Proteína Quinasa Tipo 2 Dependiente de Calcio Calmodulina/metabolismo , Colforsina , Receptores de Dopamina D2/metabolismo , Ácido gamma-Aminobutírico/metabolismo
2.
Drug Dev Res ; 85(2): e22175, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38567708

RESUMEN

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.


Asunto(s)
Antineoplásicos , Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/tratamiento farmacológico , Neoplasias Hepáticas/tratamiento farmacológico , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Flavonoides/farmacología , Flavonoides/uso terapéutico , Línea Celular Tumoral , Microambiente Tumoral
3.
Cancer Cell Int ; 23(1): 180, 2023 Aug 26.
Artículo en Inglés | MEDLINE | ID: mdl-37633886

RESUMEN

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.

4.
Cell Mol Biol (Noisy-le-grand) ; 69(7): 24-27, 2023 Jul 31.
Artículo en Inglés | MEDLINE | ID: mdl-37715439

RESUMEN

In recent years, increasing interest has been paid to using antibody-based therapies for clinical applications. However, it is unclear whether recombinant antibodies can be combined with other scientific approaches to generate innovative solutions for mitigating severe acute respiratory syndrome coronavirus 2. In this context, the increase in this virus transmission, the number of infected people, and the interaction between social and biological processes have led to a syndemic, exacerbating the public health problem. Here, we argue about recent advances in recombinant antibody strategies and the perspective of using them to face this syndemic. Thus, the most promising methods in sample readiness, potency, and reduction of manufacturing time frame have been highlighted.


Asunto(s)
COVID-19 , Humanos , SARS-CoV-2 , Sindémico , Salud Pública
5.
Cell Mol Biol (Noisy-le-grand) ; 69(3): 52-63, 2023 Mar 31.
Artículo en Inglés | MEDLINE | ID: mdl-37300689

RESUMEN

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.


Asunto(s)
Dismenorrea , Calidad de Vida , Femenino , Humanos , Dismenorrea/tratamiento farmacológico , Dimensión del Dolor
6.
Int J Mol Sci ; 25(1)2023 Dec 20.
Artículo en Inglés | MEDLINE | ID: mdl-38203252

RESUMEN

The emergence of bacterial strains displaying resistance to the currently available antibiotics is a critical global concern. These resilient bacteria can form biofilms that play a pivotal role in the failure of bacterial infection treatments as antibiotics struggle to penetrate all biofilm regions. Consequently, eradicating bacteria residing within biofilms becomes considerably more challenging than their planktonic counterparts, leading to persistent and chronic infections. Among various approaches explored, essential oils loaded in nanoparticles based on biopolymers have emerged, promising strategies that enhance bioavailability and biological activities, minimize side effects, and control release through regulated pharmacokinetics. Different available reviews analyze nanosystems and essential oils; however, usually, their main goal is the analysis of their antimicrobial properties, and progress in biofilm combat is rarely discussed, or it is not the primary objective. This review aims to provide a global vision of biofilm conformation and describes mechanisms of action attributed to each EO. Furthermore, we present a comprehensive overview of the latest developments in biopolymeric nanoparticles research, especially in chitosan- and zein-based nanosystems, targeting multidrug-resistant bacteria in both their sessile and biofilm forms, which will help to design precise strategies for combating biofilms.


Asunto(s)
Nanopartículas , Aceites Volátiles , Antibacterianos/farmacología , Biopelículas , Disponibilidad Biológica
7.
Curr Issues Mol Biol ; 44(5): 2054-2068, 2022 May 08.
Artículo en Inglés | MEDLINE | ID: mdl-35678668

RESUMEN

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.

8.
Synapse ; 76(11-12): e22246, 2022 09.
Artículo en Inglés | MEDLINE | ID: mdl-35831708

RESUMEN

Striatal medium-sized spiny neurons express mRNA and protein of GPR55 receptors that stimulate neurotransmitter release; thus, GPR55 could be sent to nigral striatal projections, where it might modulate GABA release and motor behavior. Here, we study the presence of GPR55 receptors at striato-nigral terminals, their modulation of GABA release, their signaling pathway, and their effect on motor activity. By double immunohistochemistry, we found the colocation of GPR55 protein and substance P in the dorsal striatum. In slices of the rat substantia nigra, the GPR55 agonists LPI and O-1602 stimulated [3 H]-GABA release induced by high K+ depolarization in a dose-dependent manner. The antagonists CID16020046 and cannabidiol prevented agonist stimulation in a dose-dependent way. The effect of GPR55 on nigral [3 H]-GABA release was prevented by lesion of the striatum with kainic acid, which was accompanied by a decrement of GPR55 protein in nigral synaptosomes, indicating the presynaptic location of receptors. The depletion of internal Ca2+ stores with thapsigargin did not prevent the effect of LPI on [3 H]-GABA release, but the remotion or chelation of external calcium did. Blockade of Gi, Gs, PLC, PKC, or dopamine D1 receptor signaling proteins did not prevent the effect of GPR55 on release. However, the activation of GPR55 stimulated [3 H]-cAMP accumulation and PKA activity. Intranigral unilateral injection of LPI induces contralateral turning. This turning was prevented by CID16020046, cannabidiol, and bicuculline but not by SCH 23390. Our data indicate that presynaptic GPR55 receptors stimulate [3 H]-GABA release at striato-nigral terminals through [3 H]-cAMP production and stimulate motor behavior.


Asunto(s)
Cannabidiol , Receptores de Cannabinoides , Receptores Acoplados a Proteínas G , Receptores Presinapticos , Animales , Compuestos de Azabiciclo , Benzoatos , Bicuculina/farmacología , Calcio/metabolismo , Cannabidiol/metabolismo , Cannabidiol/farmacología , Ácido Kaínico/metabolismo , Ácido Kaínico/farmacología , Neurotransmisores/farmacología , ARN Mensajero/metabolismo , Ratas , Receptores de Cannabinoides/metabolismo , Receptores de Dopamina D1/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Receptores Presinapticos/metabolismo , Sustancia P/metabolismo , Sustancia Negra/metabolismo , Tapsigargina/metabolismo , Tapsigargina/farmacología , Ácido gamma-Aminobutírico/metabolismo
9.
J Nanobiotechnology ; 20(1): 413, 2022 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-36109747

RESUMEN

Parkinson's disease (PD) significantly affects patients' quality of life and represents a high economic burden for health systems. Given the lack of safe and effective treatments for PD, drug repositioning seeks to offer new medication alternatives, reducing research time and costs compared to the traditional drug development strategy. This review aimed to collect evidence of drugs proposed as candidates to be reused in PD and identify those with the potential to be reformulated into nanocarriers to optimize future repositioning trials. We conducted a detailed search in PubMed, Web of Science, and Scopus from January 2015 at the end of 2021, with the descriptors "Parkinson's disease" and "drug repositioning" or "drug repurposing". We identified 28 drugs as potential candidates, and six of them were found in repositioning clinical trials for PD. However, a limitation of many of these drugs to achieve therapeutic success is their inability to cross the blood-brain barrier (BBB), as is the case with nilotinib, which has shown promising outcomes in clinical trials. We suggest reformulating these drugs in biodegradable nanoparticles (NPs) based on lipids and polymers to perform future trials. As a complementary strategy, we propose functionalizing the NPs surface by adding materials to the surface layer. Among other advantages, functionalization can promote efficient crossing through the BBB and improve the affinity of NPs towards certain brain regions. The main parameters to consider for the design of NPs targeting the central nervous system are highlighted, such as size, PDI, morphology, drug load, and Z potential. Finally, current advances in the use of NPs for Parkinson's disease are cited.


Asunto(s)
Enfermedad de Parkinson , Reposicionamiento de Medicamentos , Humanos , Lípidos , Nanotecnología , Enfermedad de Parkinson/tratamiento farmacológico , Preparaciones Farmacéuticas , Polímeros/uso terapéutico , Calidad de Vida
10.
Genes Immun ; 22(1): 24-34, 2021 05.
Artículo en Inglés | MEDLINE | ID: mdl-33531683

RESUMEN

Sepsis is a life-threatening organ dysfunction condition caused by a dysregulated response to an infection that is common among patients with moderate to severe burn injury. Previously, genomic variants in Toll-like receptor 4 (TLR4), a key innate immunity receptor, have been associated with sepsis and infection susceptibility. In this study, the association of six TLR4 SNPs with sepsis after burn injury was tested in the Mexican mestizo population. We found that the rs2737190 polymorphism is associated with sepsis after burn trauma. Interestingly, the G allele and GG genotype were associated with a lower risk of developing sepsis. Since the rs2737190 SNP is in the promoter region of the TLR4 gene, we analyzed the possibility that this polymorphism regulates the TLR4 pathway. We cultured peripheral blood mononuclear cells from different genotype carriers and found, after stimulation with LPS, that carriers of the GG genotype showed a higher expression of TLR4, IL6, and TNFα than AA genotype carriers. The results suggest that the GG genotype produces an increase in the TLR4 expression, and therefore an improvement in the immune response. We conclude that the rs2737190 polymorphism may become a useful marker for genetic studies of sepsis in patients after a burn injury.


Asunto(s)
Quemaduras , Sepsis , Quemaduras/complicaciones , Quemaduras/genética , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Leucocitos Mononucleares , Polimorfismo de Nucleótido Simple , Sepsis/genética , Receptor Toll-Like 4/genética
11.
Cancer Cell Int ; 21(1): 649, 2021 Dec 04.
Artículo en Inglés | MEDLINE | ID: mdl-34863151

RESUMEN

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(3): 113-117, 2021 Nov 25.
Artículo en Inglés | MEDLINE | ID: mdl-34933725

RESUMEN

Chitosan and poly(3-hydroxybutyrate) are non-toxic, biodegradable, and biocompatible polymers extensively used in regenerative medicine. However, it is unknown whether the chemical combination of these polymers can produce a biomaterial that induces an appropriate cellular response in vitro in mammalian cells. This study aimed to test the ability of a novel salt-leached polyurethane scaffold of chitosan grafted with poly(3-hydroxybutyrate) to support the growth of three mammalian cell lines of different origin: a) HEK-293 cells, b) i28 mouse myoblasts, and c) human dermal fibroblasts. The viability of the cells was assessed by either evaluation of their capacity to maintain the expression of the green fluorescent protein by adenoviral transduction or by esterase activity and plasma membrane integrity. The results indicated that the three cell lines attached well to the scaffold; however, when i28 cells were induced to differentiate, they did not produce morphologically distinct myofibers, and cell growth ceased. In conclusion, the findings reveal that, altogether, these observations suggest that this foam scaffold supports cell growth and proliferation but may not apply to all cell types. Hence, one crucial question yet to be resolved is a poly (saccharide-ester-urethane) derivative with a nano-topography that elicits a similar cellular response for different biological environments.


Asunto(s)
Poliésteres/química , Polisacáridos/química , Poliuretanos/química , Ingeniería de Tejidos/métodos , Andamios del Tejido/química , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología , Diferenciación Celular/efectos de los fármacos , Línea Celular , Proliferación Celular/efectos de los fármacos , Fibroblastos/citología , Fibroblastos/metabolismo , Células HEK293 , Humanos , Microscopía Confocal/métodos , Microscopía Fluorescente/métodos , Mioblastos/citología , Mioblastos/metabolismo
13.
Cell Mol Biol (Noisy-le-grand) ; 67(1): 101-105, 2021 Jan 31.
Artículo en Inglés | MEDLINE | ID: mdl-34817361

RESUMEN

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.


Asunto(s)
Encéfalo/efectos de los fármacos , Curcumina/administración & dosificación , Nanopartículas/administración & dosificación , Enfermedad de Parkinson/tratamiento farmacológico , Animales , Disponibilidad Biológica , Encéfalo/metabolismo , Curcumina/química , Curcumina/farmacocinética , Liberación de Fármacos , Glutatión Peroxidasa/metabolismo , Humanos , NADPH Oxidasas/antagonistas & inhibidores , NADPH Oxidasas/metabolismo , Nanopartículas/química , Fármacos Neuroprotectores/administración & dosificación , Fármacos Neuroprotectores/química , Fármacos Neuroprotectores/farmacocinética , Enfermedad de Parkinson/metabolismo , Especies Reactivas de Oxígeno/antagonistas & inhibidores , Especies Reactivas de Oxígeno/metabolismo , Superóxido Dismutasa/metabolismo , Resultado del Tratamiento , Regulación hacia Arriba/efectos de los fármacos
14.
Cell Mol Biol (Noisy-le-grand) ; 67(1): 96-100, 2021 Jan 31.
Artículo en Inglés | MEDLINE | ID: mdl-34817362

RESUMEN

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.


Asunto(s)
Productos Biológicos/farmacología , Infecciones Oportunistas/prevención & control , Cicatrización de Heridas/efectos de los fármacos , Infección de Heridas/prevención & control , Heridas y Lesiones/prevención & control , Productos Biológicos/química , Humanos , Hidrogeles/química , Hidrogeles/farmacología , Membranas Artificiales , Infecciones Oportunistas/microbiología , Plastificantes/química , Plastificantes/farmacología , Sustancias Protectoras/química , Sustancias Protectoras/farmacología , Infección de Heridas/microbiología , Heridas y Lesiones/microbiología
15.
Cell Mol Biol (Noisy-le-grand) ; 67(1): 89-95, 2021 Jan 31.
Artículo en Inglés | MEDLINE | ID: mdl-34817363

RESUMEN

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.


Asunto(s)
Clonixina/análogos & derivados , Lisina/análogos & derivados , Dolor/tratamiento farmacológico , Enfermedades Periodontales/tratamiento farmacológico , Polisacáridos Bacterianos/química , Analgésicos/farmacocinética , Analgésicos/uso terapéutico , Clonixina/farmacocinética , Clonixina/uso terapéutico , Liberación de Fármacos , Excipientes/química , Humanos , Cinética , Lisina/farmacocinética , Lisina/uso terapéutico , Membranas Artificiales , Microscopía Electrónica de Rastreo , Dolor/complicaciones , Enfermedades Periodontales/complicaciones , Polímeros/química , Polisacáridos Bacterianos/ultraestructura , Temperatura , Termogravimetría/métodos
16.
Cell Mol Biol (Noisy-le-grand) ; 67(1): 80-88, 2021 Jan 31.
Artículo en Inglés | MEDLINE | ID: mdl-34817364

RESUMEN

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.


Asunto(s)
Gardnerella vaginalis/efectos de los fármacos , Metronidazol/uso terapéutico , Polisacáridos Bacterianos/química , Vagina/efectos de los fármacos , Vaginosis Bacteriana/tratamiento farmacológico , Antibacterianos/administración & dosificación , Antibacterianos/farmacocinética , Antibacterianos/uso terapéutico , Liberación de Fármacos , Femenino , Gardnerella vaginalis/fisiología , Humanos , Concentración de Iones de Hidrógeno , Membranas Artificiales , Metronidazol/administración & dosificación , Metronidazol/farmacocinética , Microscopía Electrónica de Rastreo , Polímeros/química , Polisacáridos Bacterianos/ultraestructura , Temperatura , Termogravimetría/métodos , Resultado del Tratamiento , Vagina/microbiología , Vaginosis Bacteriana/microbiología
17.
Cell Mol Biol (Noisy-le-grand) ; 67(1): 73-79, 2021 Jan 31.
Artículo en Inglés | MEDLINE | ID: mdl-34817365

RESUMEN

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.


Asunto(s)
Rayos gamma , Hidrogeles/efectos de la radiación , Polímeros/efectos de la radiación , Polisacáridos Bacterianos/efectos de la radiación , Povidona/efectos de la radiación , Hidrogeles/síntesis química , Hidrogeles/química , Microscopía Electrónica de Rastreo , Modelos Químicos , Estructura Molecular , Polímeros/síntesis química , Polímeros/química , Polisacáridos Bacterianos/síntesis química , Polisacáridos Bacterianos/química , Porosidad , Povidona/síntesis química , Povidona/química , Espectroscopía Infrarroja por Transformada de Fourier/métodos , Temperatura , Termogravimetría/métodos
18.
Cell Mol Biol (Noisy-le-grand) ; 67(1): 64-72, 2021 Jan 31.
Artículo en Inglés | MEDLINE | ID: mdl-34817366

RESUMEN

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.


Asunto(s)
Materiales Biocompatibles/metabolismo , Elastina/metabolismo , Apósitos Oclusivos , Polimerizacion/efectos de la radiación , Povidona/metabolismo , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología , Rastreo Diferencial de Calorimetría/métodos , Proliferación Celular/efectos de los fármacos , Células Cultivadas , Elastina/química , Elastina/ultraestructura , Fibroblastos/citología , Fibroblastos/efectos de los fármacos , Humanos , Hidrogeles/química , Hidrogeles/metabolismo , Hidrogeles/farmacología , Microscopía Electrónica de Rastreo , Povidona/química , Povidona/farmacología , Espectroscopía Infrarroja por Transformada de Fourier/métodos , Termogravimetría/métodos , Cicatrización de Heridas/efectos de los fármacos
19.
Cell Mol Biol (Noisy-le-grand) ; 67(1): 58-63, 2021 Jan 31.
Artículo en Inglés | MEDLINE | ID: mdl-34817367

RESUMEN

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.


Asunto(s)
Materiales Biocompatibles/efectos de la radiación , Rayos gamma , Ácido Hialurónico/efectos de la radiación , Polímeros/efectos de la radiación , Alcohol Polivinílico/efectos de la radiación , Materiales Biocompatibles/síntesis química , Materiales Biocompatibles/farmacología , Movimiento Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Fibroblastos/citología , Fibroblastos/efectos de los fármacos , Humanos , Ácido Hialurónico/síntesis química , Ácido Hialurónico/ultraestructura , Microscopía Electrónica de Rastreo , Modelos Químicos , Estructura Molecular , Polímeros/síntesis química , Polímeros/farmacología , Alcohol Polivinílico/síntesis química , Alcohol Polivinílico/farmacología , Espectroscopía Infrarroja por Transformada de Fourier/métodos , Ingeniería de Tejidos/métodos
20.
Dermatol Ther ; 34(1): e14628, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-33277959

RESUMEN

Lamellar ichthyosis (LI) is a genetic skin disorder characterized by dark brown scales, palmoplantar hyperkeratosis, pain, and itching. LI severity could have implications in psychological aspects, causing depression and impairment in the quality of life (QoL) of patients. In this study, we used the Congenital Ichthyosis Severity Index, the Depression Beck Inventory-II (DBI-II), and the Dermatologic Life Quality Index (DLQI) to assess severity, level of depression, and impairment in QoL in a group of patients with LI. We observed that the majority of the patients presented a high severity level concerning the presence of scales (57.7%), while for erythema and alopecia, the severity was less 80% of the analyzed patients presented depression, while only 20.8% of individuals of the control group presented it (P < .001, OR = 15.2). While for QoL, only 4.3% of the patients did not exhibit any impairment. Finally, the increase in the score obtained in DBI-II was correlated with the DLQI score (rs = 0.663, P = .0014). Our results suggest that patients with LI have an increased risk of suffering depression and impairment in their QoL; thus, the management of their disease should be performed from a multidisciplinary perspective to improve the global aspects of their lives.


Asunto(s)
Ictiosis Lamelar , Calidad de Vida , Alopecia , Depresión/diagnóstico , Depresión/epidemiología , Eritema , Humanos , Ictiosis Lamelar/diagnóstico , Ictiosis Lamelar/epidemiología
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