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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.
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Estrés del Retículo Endoplásmico , Estrés Oxidativo , Humanos , Enfermedad Crónica , Inflamación , Muerte Celular , AutofagiaRESUMEN
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.
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Enfermedad de Parkinson , Oligoelementos , Humanos , Enfermedad de Parkinson/patología , Cobre , Metales , Hierro , Estrés Oxidativo , Oxidación-Reducción , Neuronas Dopaminérgicas/patología , Quelantes/farmacología , Quelantes/uso terapéuticoRESUMEN
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.
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Remodelación de las Vías Aéreas (Respiratorias) , Asma/metabolismo , Asma/patología , Mucosa Intestinal/metabolismo , Mucosa Intestinal/microbiología , Lactococcus lactis/fisiología , Probióticos/administración & dosificación , Factor de Crecimiento Transformador beta/biosíntesis , Remodelación de las Vías Aéreas (Respiratorias)/inmunología , Animales , Asma/etiología , Asma/prevención & control , Citocinas/metabolismo , Modelos Animales de Enfermedad , Inmunoglobulina E/sangre , Inmunoglobulina E/inmunología , Mediadores de Inflamación/metabolismo , Leucocitos/inmunología , Leucocitos/metabolismo , Ovalbúmina/inmunología , RatasRESUMEN
Caloric restriction (CR) and its related alternatives have been shown to be the only interventions capable of extending lifespan and decreasing the risk of cancer, along with a reduction in burden in pre-clinical trials. Nevertheless, the results from clinical trials have not been as conclusive as the pre-clinical results. Recognizing the challenges associated with long-term fasting, the application of caloric restriction mimetics (CRMs), pharmacological agents that mimic the molecular effects of CR, to harness the potential benefits while overcoming the practical limitations of fasting has resulted in an interesting alternative. This review synthesizes the findings of diverse clinical trials evaluating the safety and efficacy of CR and CRMs. In dietary interventions, a fast-mimicking diet was the most tolerated to reduce tumoral growth markers and chemotherapy side effects. CRMs were well tolerated, and metformin and aspirin showed the most promising effect in reducing cancer risk in a selected group of patients. The application of CR and/or CRMs shows promising effects in anti-cancer therapy; however, there is a need for more evidence to safely include these interventions in standard-of-care therapies.
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Anterior cruciate ligament injuries are frequent afflictions related to sports or physical trauma. Autograft reconstruction strategies cause secondary injury to the patient. One alternative, supported by clinical evidence, is porcine xenografts. For clinical use, xenografts must be conditioned to avoid immune rejection. The most widely accepted procedure is tissue decellularization. We analyzed three decellularization strategies: the application of the anionic detergent sodium dodecyl sulfate (SDS), sonication, and freezing and thawing cycles. The treated tissues were evaluated histologically using H&E, Masson's trichrome, Verhoeff-van Gieson staining, and DAPI for fluorescent staining of nuclei. Finally, collagen fiber preservation was evaluated by quantifying this protein by colorimetry. The most efficient decellularization techniques were sonication and SDS. Collagen fibers were preserved in all experimental conditions.
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Peroxiredoxins (Prdxs) are thiol-dependent enzymes that scavenge peroxides. Previously, we found that Prdxs were hyperoxidized in a Parkinson's disease model induced by paraquat (PQ), which led to their inactivation, perpetuating reactive oxygen species (ROS) formation. Herein, we evaluated the redox state of the typical 2-Cys-Prx subgroup. We found that PQ induces ROS compartmentalization in different organelles, reflected by the 2-Cys-Prdx hyperoxidation pattern detected by redox eastern blotting. 2-Cys Prdxs are most vulnerable to hyperoxidation, while atypical 2-Cys Peroxiredoxin 5 (Prdx5) is resistant and is expressed in multiple organelles, such as mitochondria, peroxisomes, and cytoplasm. Therefore, we overexpressed human Prdx5 in the dopaminergic SHSY-5Y cell line using the adenoviral vector Ad-hPrdx5. Prdx5 overexpression was confirmed by western blotting and immunofluorescence (IF) and effectively decreased PQ-mediated mitochondrial and cytoplasmic ROS assessed with a mitochondrial superoxide indicator and DHE through IF or flow cytometry. Decreased ROS mediated by Prdx5 in the main subcellular compartments led to overall cell protection against PQ-induced cell death, which was demonstrated by flow cytometry using Annexin V labeling and 7-AAD. Therefore, Prdx5 is an attractive therapeutic target for PD, as its overexpression protects dopaminergic cells from ROS and death, which warrants further experimental animal studies for its subsequent application in clinical trials.
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Estrés Oxidativo , Paraquat , Animales , Humanos , Especies Reactivas de Oxígeno/metabolismo , Especies Reactivas de Oxígeno/farmacología , Paraquat/farmacología , Peroxirredoxinas/genética , Peroxirredoxinas/metabolismo , Peroxirredoxinas/farmacología , Muerte Celular/genéticaRESUMEN
BACKGROUND: Trehalose is a non-reducing disaccharide synthesized by lower organisms. It has recently received special attention because of its neuroprotective properties by stimulating autophagy in Parkinson's disease (PD) models. Therefore, evaluating whether trehalose affects metabolic organs is vital to determine its neurotherapeutic safety. METHODS: We validated the trehalose neuroprotective dosage in a PD model induced with intraperitoneal paraquat administration twice weekly for 7 weeks. One week before paraquat administration, mice were treated with trehalose in the drinking water and continued along with paraquat treatment. Histological and morphometrical analyses were conducted on the organs involved in trehalose metabolism, including the liver, pancreas, and kidney. RESULTS: Paraquat-induced dopaminergic neuronal loss was significantly decreased by trehalose. After trehalose treatment, the liver morphology, the mononucleated/binucleated hepatocytes percentage, and sinusoidal diameter remained unchanged in each liver lobes. Endocrine and exocrine pancreas's histology was not affected, nor was any fibrotic process observed. The islet of Langerhans's structure was preserved when analyzing the area, the largest and smallest diameter, and circularity. Renal morphology remained undamaged, and no changes were identified within the glomerular basement membrane. The renal corpuscle structure did not suffer alterations in the Bowman's space, area, diameter, circularity, perimeter, and cellularity. Besides, the renal tubular structures's luminal area and internal and external diameter were preserved. CONCLUSION: Our study demonstrates that systemic trehalose administration preserved the typical histological architecture of the organs involved in its metabolism, supporting its safety as a potential neuroprotective agent.
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Paraquat , Trehalosa , Ratones , Animales , Trehalosa/farmacología , Trehalosa/uso terapéutico , Riñón , Hígado , PáncreasRESUMEN
Parkinson's disease (PD) is characterized by the loss of dopaminergic neurons in the substantia nigra pars compact (SNpc), and no effective treatment has yet been established to prevent PD. Neurotrophic factors, such as cerebral dopamine neurotrophic factor (CDNF), have shown a neuroprotective effect on dopaminergic neurons. Previously, we developed a cell-penetrating-peptide-based delivery system that includes Asn194Lys mutation in the rabies virus glycoprotein-9R peptide (mRVG9R), which demonstrated a higher delivery rate than the wild-type. In this study, using a mouse PD-like model, we evaluated the intrastriatal mRVG9R-KP-CDNF gene therapy through motor and cognitive tests and brain cell analysis. The mRVG9R-KP-CDNF complex was injected into the striatum on days 0 and 20. To induce the PD-like model, mice were intraperitoneally administered Paraquat (PQ) twice a week for 6 weeks. Our findings demonstrate that mRVG9R-KP-CDNF gene therapy effectively protects brain cells from PQ toxicity and prevents motor and cognitive dysfunction in mice. We propose that the mRVG9R-KP-CDNF complex inhibits astrogliosis and microglia activation, safeguarding dopaminergic neurons and oligodendrocytes from PQ-induced damage. This study presents an efficient CDNF delivery system, protecting neurons and glia in the nigrostriatal pathway from PQ-induced damage, which is known to lead to motor and cognitive dysfunction in neurodegenerative diseases such as PD.
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Enfermedad de Parkinson , Animales , Enfermedad de Parkinson/terapia , Enfermedad de Parkinson/metabolismo , Factores de Crecimiento Nervioso/genética , Factores de Crecimiento Nervioso/metabolismo , Sustancia Negra , Modelos Animales de Enfermedad , Neuronas DopaminérgicasRESUMEN
The endoplasmic reticulum (ER) is a key organelle in cell homeostasis and cell health through antigen presentation to immune cells. Thus, the ER has become a therapeutic target to induce cellular immune responses. We previously reported the antitumor effect of a DNA vaccine that expresses the E7 antigen fused to the cyclooxygenase-2 (COX-2) protein. This inflammation-related enzyme contains a degradation cassette associated with the endoplasmic reticulum-associated degradation (ERAD) pathway. To avoid the use of full-length COX-2 and any risk of adverse effects due to the activity of its catalytic site, we designed new versions of the fusion protein. These new constructs encode the E7 antigen fused to the signal peptide and the ERAD sequence of COX-2 with or without the membrane-binding domain (MBD) as well as deletion of the catalytic site. We evaluated the antigen-specific antitumor effect of these DNA constructs in murine prophylactic and therapeutic cancer models. These assays showed that the ERAD cassette is the minimum sequence in the COX-2 protein that induces an antitumor effect when fused to the E7 antigen with the advantage of eliminating any potential adverse effects from the use of full-length COX-2.
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Degradación Asociada con el Retículo Endoplásmico , Vacunas de ADN , Animales , Ratones , Ciclooxigenasa 2 , Retículo EndoplásmicoRESUMEN
The sympathetic nervous system and the immune system are responsible for producing neurotransmitters and cytokines that interact by binding to receptors; due to this, there is communication between these systems. Liver immune cells and nerve fibres are systematically distributed in the liver, and the partial overlap of both patterns may favour interactions between certain elements. Dendritic cells are attached to fibroblasts, and nerve fibres are connected via the dendritic cell-fibroblast complex. Receptors for most neuroactive substances, such as catecholamines, have been discovered on dendritic cells. The sympathetic nervous system regulates hepatic fibrosis through sympathetic fibres and adrenaline from the adrenal glands through the blood. When there is liver damage, the sympathetic nervous system is activated locally and systemically through proinflammatory cytokines that induce the production of epinephrine and norepinephrine. These neurotransmitters bind to cells through α-adrenergic receptors, triggering a cellular response that secretes inflammatory factors that stimulate and activate hepatic stellate cells. Hepatic stellate cells are key in the fibrotic process. They initiate the overproduction of extracellular matrix components in an active state that progresses from fibrosis to liver cirrhosis. It has also been shown that they can be directly activated by norepinephrine. Alpha and beta adrenoblockers, such as carvedilol, prazosin, and doxazosin, have recently been used to reverse CCl4-induced liver cirrhosis in rodent and murine models.KEY MESSAGESNeurotransmitters from the sympathetic nervous system activate and increase the proliferation of hepatic stellate cells.Hepatic fibrosis and cirrhosis treatment might depend on neurotransmitter and hepatic nervous system regulation.Strategies to reduce hepatic stellate cell activation and fibrosis are based on experimentation with α-adrenoblockers.
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Células Estrelladas Hepáticas , Neuroinmunomodulación , Ratones , Humanos , Animales , Células Estrelladas Hepáticas/metabolismo , Células Estrelladas Hepáticas/patología , Cirrosis Hepática/patología , Hígado/metabolismo , Norepinefrina/metabolismo , Fibrosis , Citocinas , Neurotransmisores/metabolismoRESUMEN
Recently, the interest in using nucleic acids for therapeutic applications has been increasing. DNA molecules can be manipulated to express a gene of interest for gene therapy applications or vaccine development. Plasmid DNA can be developed to treat different diseases, such as infections and cancer. In most cancers, the immune system is limited or suppressed, allowing cancer cells to grow. DNA vaccination has demonstrated its capacity to stimulate the immune system to fight against cancer cells. Furthermore, plasmids for cancer gene therapy can direct the expression of proteins with different functions, such as enzymes, toxins, and cytotoxic or proapoptotic proteins, to directly kill cancer cells. The progress and promising results reported in animal models in recent years have led to interesting clinical results. These DNA strategies are expected to be approved for cancer treatment in the near future. This review discusses the main strategies, challenges, and future perspectives of using plasmid DNA for cancer treatment.
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Rapamycin is the best-characterized autophagy inducer, which is related to its antiaging and neuroprotective effects. Although rapamycin is an FDA-approved drug for human use in organ transplantation and cancer therapy, its administration as an antiaging and neuroprotective agent is still controversial because of its immunosuppressive and reported side effects. Therefore, it is critical to determine whether the dose that exerts a neuroprotective effect, 35 times lower than that used as an immunosuppressant agent, harms peripheral organs. We validated the rapamycin neuroprotective dosage in a Parkinson's disease (PD) model induced with paraquat. C57BL/6 J mice were treated with intraperitoneal (IP) rapamycin (1 mg/kg) three times per week, followed by paraquat (10 mg/kg) twice per week for 6 weeks, along with rapamycin on alternate days. Rapamycin significantly decreased dopaminergic neuronal loss induced by paraquat. Since rapamycin's neuroprotective effect in a PD model was observed at 7 weeks of treatment; we evaluated its effect on the liver, kidney, pancreas, and spleen. In addition, we prolonged treatment with rapamycin for 14 weeks. Tissue sections were subjected to histochemical, immunodetection, and morphometric analysis. Chronic rapamycin administration does not affect bodyweight, survival, and liver or kidney morphology. Although the pancreas tissular architecture and cellular distribution in Langerhans islets are modified, they may be reversible. The spleen B lymphocyte and macrophage populations were decreased. Notably, the lymphocyte T population was not affected. Therefore, chronic administration of a rapamycin neuroprotective dose does not produce significant tissular alterations. Our findings support the therapeutic potential of rapamycin as a neuroprotective agent.
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Fármacos Neuroprotectores , Animales , Humanos , Inmunosupresores/efectos adversos , Ratones , Ratones Endogámicos C57BL , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/uso terapéutico , Paraquat , Sirolimus/farmacología , Sirolimus/uso terapéuticoRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Urolithiasis is the presence of stones in the kidney, ureters, bladder and/or urethra; it is the third most frequent disease of the urinary tract. Mimosa malacophylla A. Gray, is a species distributed in northern Mexico, where people traditionally use it for its diuretic effect, and to treat kidney diseases; however, no scientific reports have been found in relation to its antiurolithic properties. AIM OF THE STUDY: This study aimed to obtain a qualitative phytochemical profile of the methanolic extract (ME) of M. malacophylla, and to evaluate its potential cytotoxic effect in vitro and its antiurolithic activity in vivo. MATERIAL AND METHODS: Phytochemical screening was performed to demonstrate the presence of secondary metabolite groups in the methanolic extract of M. malacophylla. In vitro cytotoxicity assays (MTT and nucleotide labeling with DAPI) were performed to evaluate the effect of the extract on kidney cell lines. Urolithiasis was induced in the bladder of Wistar rats introducing zinc disks for the calculus formation and exposed to three concentrations of ME. RESULTS: Phytochemical screening showed phenols, steroids, terpenoids and carbohydrates. In vitro analysis demonstrated that concentrations below 300 µg/mL of ME did not produce a cytotoxic effect on renal Vero and HEK-293 cells. In vivo analysis of 15 days of exposition, revealed that the extract at concentrations of 50 mg/kg to 150 mg/kg were effective as an antiurolithic treatment, and did not produce morphological alterations in kidney or bladder in murine model of induced urolithiasis. CONCLUSIONS: The antiurolithic activity may be attributed to the presence of flavonoids, steroids and terpenes detected in the phytochemical screening which have been reported to possess this activity. These results could be useful to evaluate new alternatives and their potential therapeutic effect to treat renal or urinary affections.
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Mimosa , Urolitiasis , Animales , Células HEK293 , Humanos , Riñón , Metanol/farmacología , Ratones , Extractos Vegetales/química , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Ratas , Ratas Wistar , Vejiga Urinaria , Urolitiasis/inducido químicamenteRESUMEN
Oxidative stress is considered one of the pathological mechanisms that cause Parkinson's disease (PD), which has led to the investigation of several antioxidants molecules as a potential therapeutic treatment against the disease. Although preclinical studies have demonstrated the efficacy of these compounds to maintain neuronal survival and activity in PD models, these results have not been reflected in clinical trials, antioxidants have not been able to act as disease modifiers in terms of clinical symptoms. Translational medicine currently faces the challenge of redesigning clinical trials to standardize criteria when testing molecules to reduce responses' variability. Herein, we discuss current challenges and opportunities regarding several non-enzymatic antioxidants' therapeutic molecules for PD patients' potential treatment.
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It has been previously reported that targeting and retaining antigens in the endoplasmic reticulum (ER) can induce an ER stress response. In this study, we evaluated the antitumor effect of E7 antigen fused to an ERresident protein, cyclooxygenase-2, which possesses a 19-aminoacid cassette that directs it to the endoplasmic reticulum-associated protein degradation (ERAD) pathway. The featured DNA constructs, COX2-E7 and COX2-E7ΔERAD, with a deletion in the 19-aminoacid cassette, were used to evaluate the importance of this sequence. In vitro analysis of protein expression and ER localisation were verified. We observed that both constructs induced an ER stress response. This finding correlated with the antitumor effect in mice injected with TC-1 cells and treated with different DNA constructs by biolistic vaccination. Immunisation with COX2-E7 and COX2-E7ΔERAD DNA constructs induced a significant antitumor effect in mice, without a significant difference between them, although the COX2-E7 construct induced a significant E7-specific immune response. These results demonstrate that targeting the E7 antigen to the ERAD pathway promotes a potent therapeutic antitumor effect. This strategy could be useful for the design of other antigen-specific therapies.
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Vacunas contra el Cáncer/administración & dosificación , Ciclooxigenasa 2/química , Estrés del Retículo Endoplásmico/inmunología , Proteínas E7 de Papillomavirus/inmunología , Animales , Vacunas contra el Cáncer/inmunología , Línea Celular Tumoral , Ciclooxigenasa 2/administración & dosificación , Retículo Endoplásmico/inmunología , Degradación Asociada con el Retículo Endoplásmico/inmunología , Femenino , Células HEK293 , Humanos , Neoplasias Pulmonares/inmunología , Neoplasias Pulmonares/prevención & control , Ratones , Ratones Endogámicos C57BL , Neoplasias Experimentales/inmunología , Neoplasias Experimentales/prevención & control , Vacunas de ADN/administración & dosificación , Vacunas de ADN/inmunologíaRESUMEN
Cancer is a major global public health problem and conventional chemotherapy has several adverse effects and deficiencies. As a valuable option for chemotherapy, nanomedicine requires novel agents to increase the effects of antineoplastic drugs in multiple cancer models. Since its discovery, carbon nanotubes (CNTs) are intensively investigated for their use as carriers in drug delivery applications. This study shows the development of a nanovector generated with commercial carbon nanotubes (cCNTs) that were oxidized (oxCNTs) and chemically functionalized with hyaluronic acid (HA) and loaded with carboplatin (CPT). The nanovector, oxCNTs-HA-CPT, was used as a treatment against HeLa and MDA-MB-231 human tumor cell lines. The potential antineoplastic impact of the fabricated nanovector was evaluated in human cervical adenocarcinoma (HeLa) and mammary adenocarcinoma (MDA-MB-231). The oxCNTs-HA-CPT nanovector demonstrate to have a specific antitumor effect in vitro. The functionalization with HA allows that nanovector bio-directed towards tumor cells, while the toxicity effect is attributed mainly to CPT in a dose-dependent manner.
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Carbon nanotubes (CNTs) have emerged in recent years as a potential option for drug delivery, due to their high functionalization capacity. Biocompatibility and selectivity using tissue-specific biomolecules can optimize the specificity, pharmacokinetics and stability of the drug. In this study, we design, develop and characterize a drug nanovector (oxCNTs-HA-CPT) conjugating oxidated multi-wall carbon nanotubes (oxCNTs) with hyaluronate (HA) and carboplatin (CPT) as a treatment in a lung cancer model in vitro. Subsequently, we exposed TC-1 and NIH/3T3 cell lines to the nanovectors and measured cell uptake, cell viability, and oxidative stress induction. The characterization of oxCNTs-HA-CPT reveals that on their surface, they have HA. On the other hand, oxCNTs-HA-CPT were endocytosed in greater proportion by tumor cells than by fibroblasts, and likewise, the cytotoxic effect was significantly higher in tumor cells. These results show the therapeutic potential that nanovectors possess; however, future studies should be carried out to determine the death pathways involved, as well as their effect on in vivo models.
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OBJECTIVES: A cell-penetrating peptide-based delivery system could target specific types of cells for therapeutic genes delivery. To increase the gene delivery efficiency into neuronal phenotype cells, we introduced an Asn194Lys mutation to RVG29 peptide derived from rabies virus glycoprotein and added a nuclear localization signal to enhance its nuclear import. METHODS: Mutant RVG or wild-type RVG peptide, a karyophilic peptide (KP) and a plasmid encoding green fluorescent protein (pGL) were bound by electrostatic charges to form four different kinds of RVG complexes. Immunofluorescence was used to assess the gene transfection efficiency into astrocytes, oligodendrocyte precursor cells (OPCs), SH-SY5Y, HeLa and NIH/3T3 cells. The cellular uptake mechanism of RVG29 complexes was examined using endocytosis inhibitors. KEY FINDINGS: The mRVG29 peptide has the ability to enhance the nuclear import of plasmids. The Asn194Lys mutation in RVG29 peptide of the pGL-mRVG29 complex and the addition of KP to the pGL-RVG29-KP complex increased the capacity to deliver DNA by endocytosis in astrocytes and SH-SY5Y cells. CONCLUSIONS: The complexes pGL-mRVG29 and pGL-RVG29-KP have specificity for transfecting astrocytes and SH-SY5Y cells. The karyophilic capacity of this new mRVG peptide render it promising candidate to act as gene delivery vector into the brain cells.
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Astrocitos/fisiología , Endocitosis/fisiología , Glicoproteínas/genética , Proteínas Fluorescentes Verdes/genética , Neuroblastoma/genética , Fragmentos de Péptidos/genética , Transgenes/genética , Proteínas Virales/genética , Secuencia de Aminoácidos , Animales , Animales Recién Nacidos , Asparagina/administración & dosificación , Asparagina/genética , Astrocitos/efectos de los fármacos , Células Cultivadas , Endocitosis/efectos de los fármacos , Técnicas de Transferencia de Gen , Glicoproteínas/administración & dosificación , Proteínas Fluorescentes Verdes/administración & dosificación , Lisina/administración & dosificación , Lisina/genética , Ratones , Mutación/genética , Neuroblastoma/terapia , Fragmentos de Péptidos/administración & dosificación , Proteínas Virales/administración & dosificaciónRESUMEN
Parkinson's disease is the second most important neurodegenerative disorder worldwide. It is characterized by the presence of Lewy bodies, which are mainly composed of α-synuclein and ubiquitin-bound proteins. Both the ubiquitin proteasome system (UPS) and autophagy-lysosomal pathway (ALS) are altered in Parkinson's disease, leading to aggregation of proteins, particularly α-synuclein. Interestingly, it has been observed that copper promotes the protein aggregation process. Additionally, phosphorylation of α-synuclein along with copper also affects the protein aggregation process. The interrelation among α-synuclein phosphorylation and its capability to interact with copper, with the subsequent disruption of the protein degradation systems in the neurodegenerative process of Parkinson's disease, will be analyzed in detail in this review.
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The aim of this study was to characterize and compare the morphological and histomorphometric characteristics of the pectoral fascia, fascia lata and ventral rectus sheath. Twenty cadaveric samples of these fascias were analyzed and stained with hematoxylin and eosin, orcein, Van Gieson, Masson's trichrome and Verhoeff¨s stain (1200 slides in total). Morphological evaluation, semiquantitative, morphometric and microdensitometric analysis of elastic fibers present in each of the tissues and a morphometrical analysis of tissue thickness were performed. The mean value of the pectoral fascia thickness was 612±68.13 µm; 84±246 µm for the fascia lata and 584±92 µm for the ventral rectus sheath. The area occupied by the elastic fibers in the pectoral fascia was 12.24±5.84%; 6,54±3.85% for the fascia lata and 11.11±5.26% for the ventral rectus sheath. There were no statistically significant differences when comparing the mean values between the pectoral fascia and the ventral rectus sheath (p=0.07). There were statistically significant differences when comparing the fascia lata to the pectoral fascia and the ventral rectus sheath (p≤0.001). This study reports other morphological characteristics not described in previous histological studies of the analyzed tissues. The results of the morphometric and densitometric analysis in this study reveal that the fascia lata has the fewest elastic fibers of all the tissues analyzed, and the pectoral fascia has the most. These results will be useful for the beginning of a morphological information bank of human fascias.