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1.
J Neurovirol ; 30(3): 316-326, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38600308

RESUMEN

The Coronavirus Disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) primarily targets respiratory cells, but emerging evidence shows neurological involvement, with the virus directly affecting neurons and glia. SARS-CoV-2 entry into a target cell requires co-expression of ACE2 (Angiotensin-converting enzyme-2) and TMPRSS2 (Trans membrane serine protease-2). Relevant literature on human neurological tissue is sparse and mostly focused on the olfactory areas. This prompted our study to map brain-wide expression of these entry proteins and assess age-related changes. The normal brain tissue samples were collected from cerebral cortex, hippocampus, basal ganglia, thalamus, hypothalamus, brain stem and cerebellum; and were divided into two groups - up to 40 years (n = 10) and above 40 years (n = 10). ACE2 and TMPRSS2 gene expression analysis was done using qRT-PCR and protein co-expression was seen by immunofluorescence. The ACE2 and TMPRSS2 gene expression was observed to be highest in hypothalamus and thalamus regions, respectively. Immunoreactivity for both ACE-2 and TMPRSS2 was observed in all examined brain regions, confirming the presence of these viral entry receptors. Co-localisation was maximum in hypothalamus. Our study did not find any trend related to different age groups. The expression of both these viral entry receptors suggests that normal human brain is susceptibility to SARS-CoV-2, perhaps which could be related to the cognitive and neurological impairment that occur in patients.


Asunto(s)
Enzima Convertidora de Angiotensina 2 , Encéfalo , COVID-19 , SARS-CoV-2 , Serina Endopeptidasas , Humanos , Serina Endopeptidasas/genética , Serina Endopeptidasas/metabolismo , Enzima Convertidora de Angiotensina 2/genética , Enzima Convertidora de Angiotensina 2/metabolismo , COVID-19/metabolismo , COVID-19/virología , COVID-19/genética , COVID-19/patología , SARS-CoV-2/genética , SARS-CoV-2/patogenicidad , Encéfalo/virología , Encéfalo/metabolismo , Encéfalo/patología , Persona de Mediana Edad , Adulto , Masculino , Femenino , Anciano , Internalización del Virus
2.
Artículo en Inglés | MEDLINE | ID: mdl-36777176

RESUMEN

Background: The primary objective of this study was to determine the outcome of emergency surgery in coronavirus disease 2019 (COVID-19) patients with regard to presently existing physical status, and highlight its subspecialty distribution. Methods: This retrospective observational study was done on all patients who underwent emergency surgery between March 2020 and Dec 2021 and were positive for COVID-19. Data collection included the age of the patients, gender, diagnosis, the type of surgery performed, and outcome. Physical status was assessed, as per Modified Medical Research Council Dyspnoea Scale (MMRC) and Metabolic Equivalent Scale (METS). Results: A total of 89 patients were analyzed from March 2020 to Dec 2021. There were 63 females and 26 males. The average age of the males was 53.8 ± 8.9 years and the average age of the females was 29.1 ± 4.6 years. The maximum number of surgeries done was lower segment cesarean section (57.3%). 55 out of 60 (91%) cases had a good grade on the MMRC scale (Grade 0 and 1). 3 patients had Grade 4 MMRC scale and all 3 were oncology cases. As per the METS scale, 56/60 (93.3%) patients had METS >10. Conclusion: This study has demonstrated that 55 out of 60 (91%) of cases had a good grade on the MMRC scale (Grade 0 and 1) 6 months to 1-year post-surgery. As per the METS scale, 56/60 (93.3%) patients had METS >10. Most of the cases were asymptomatic COVID-19-positive and presently have good physical status as determined by the study.

3.
World J Surg Oncol ; 20(1): 403, 2022 Dec 20.
Artículo en Inglés | MEDLINE | ID: mdl-36539838

RESUMEN

BACKGROUND: The present study aims to evaluate the survival status of patients with gallbladder cancer (GBC) and explore the prognostic factors for the improvement and preventions. METHODS: The study consists of 176 patients with clinically diagnosed gallbladder cancer; the study was conducted between 2019 and 2021 registered at Kamala Nehru Memorial Cancer Hospital, Prayagraj, India. The survival rates were analyzed by the Kaplan-Meier method; survival rate difference was analyzed by log-rank test, prognosis factors; and hazard ratio for mortality outcomes was estimated using Cox regression method. RESULTS: The overall median survival time of patients was 5 months with the 1-year, 2-year, and 3-year survival rates of 24.4%, 8.5%, and 4.5%, respectively. The 3-year survival for patients with jaundice was 2.9%, liver infiltration (4.2%), gallstones (0.8%), and with advanced tumor grade (1.4%). Elderly GBC patients had lower survival rates (3.8%), while the 3-year overall survival for patients residing in urban areas dropped to zero. No patients in the tumor stage (T3/T4) and with distance metastasis stage survived in 3 years, while only 1.1% of patients with advanced nodal stage survived. On receiving surgery and radiation therapy, the 3-year survival rate increased to 19.5% and 35%, respectively. The results of multivariate analysis showed that urban region (HR = 1.568, p = 0.040), gallstone or not (1.571, p = 0.049), N stage (HR = 1.468, p = 0.029), and M stage (HR = 2.289, p < 0.0001) were independent risk factors for prognosis, while surgery or not (HR = 0.573, p = 0.030) was the protective factor for the prognosis of GBC. CONCLUSION: The overall survival of GBC in the Gangetic belt is poor. The geographical region of patients, gallstones, and N and M stage was the risk factors for prognosis, while surgery or not was the protective factor for the prognosis of GBC.


Asunto(s)
Carcinoma , Neoplasias de la Vesícula Biliar , Cálculos Biliares , Humanos , Anciano , Pronóstico , Neoplasias de la Vesícula Biliar/patología , Cálculos Biliares/complicaciones , Cálculos Biliares/cirugía , Cálculos Biliares/patología , Modelos de Riesgos Proporcionales , Carcinoma/patología , Estadificación de Neoplasias , Análisis de Supervivencia
4.
Fish Physiol Biochem ; 46(2): 725-738, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-31848826

RESUMEN

In hilsa (Tenualosa ilisha), pseudobranch comprises a row of parallel filaments bear numerous leaf-like lamellae arranged on both sides throughout its length. The purpose of this study was to elucidate involvement of pseudobranchial Na+, K+-ATPase (NKA) 1 α-subunit, and carbonic anhydrase (CA) in concert with H+-ATPase (HAT) compared to their branchial counterparts in freshwater acclimation of hilsa during spawning migration from off-shore of the Bay of Bengal to the Bhagirathi-Hooghly zones of the Ganga river system in India. Adult hilsa fish were collected from seawater (SW), freshwater 1 (FW1), and freshwater 2 (FW2) locations, where the salinity level was 26-28‰, 1-5‰, and 0-0.04‰, respectively. Hilsa migrating through freshwater showed a consistent decrease in the plasma osmolality, sodium (Na+) and chloride (Cl-) ion levels indicates unstable ionic homeostasis. The mRNA expression and activity of NKA 1 α-subunit in pseudobranch as well as in true gills declined with the migration to upstream locations. The pseudobranchial CA activity almost mirrors its branchial counterpart most notably while hilsa entered the freshwater zone, in the upstream river suggesting its diverse role in hypo-osmotic regulatory acclimation. Nevertheless, the H+-ATPase activity of both the tissues increased with the freshwater entry and remained similar during up-river movement into the freshwater environment. The results confirm that the pseudobranchial NKA 1 α-subunit mRNA expression and activity mimic its branchial counterpart in the process of ionoregulatory acclimation during migration through salt barriers. Also, the increase in the activities of pseudobranchial and branchial CA in concert with H+-ATPase (HAT) during freshwater acclimation of hilsa suggests their critical involvement in ion uptake.


Asunto(s)
Anhidrasas Carbónicas/metabolismo , Peces/fisiología , ATPasas de Translocación de Protón/metabolismo , ATPasa Intercambiadora de Sodio-Potasio/metabolismo , Migración Animal , Animales , Branquias/metabolismo , Ríos , Salinidad
5.
J Cell Physiol ; 234(3): 3007-3019, 2019 03.
Artículo en Inglés | MEDLINE | ID: mdl-30206943

RESUMEN

An elevated level of homocysteine (Hcy) leads to hyperhomocysteinemia (HHcy), which results in vascular dysfunction and pathological conditions identical to stroke symptoms. Hcy increases oxidative stress and leads to increase in blood-brain barrier permeability and leakage. Hydrogen sulfide (H2 S) production during the metabolism of Hcy has a cerebroprotective effect, although its effectiveness in Hcy-induced neurodegeneration and neurovascular permeability is less explored. Therefore, the current study was designed to perceive the neuroprotective effect of exogenous H 2 S against HHcy, a cause of neurodegeneration. To test this hypothesis, we used four groups of mice: control, Hcy, control + sodium hydrosulfide hydrate (NaHS), and Hcy + NaHS, and an HHcy mice model in Swiss albino mice by giving a dose of 1.8 g of dl-Hcy/L in drinking for 8-10 weeks. Mice that have 30 µmol/L Hcy were taken for the study, and a H 2 S supplementation of 20 µmol/L was given for 8 weeks to all groups of mice. HHcy results in the rise of the levels of superoxide and nitrite, although a concomitant decrease in the level of superoxide dismutase, catalase, glutathione peroxidase, reduced glutathione, and arginase in oxidative stress and a concomitant decrease in the endogenous level of H 2 S. Although H 2 S supplementation ameliorated, the effect of HHcy and the levels of H 2 S returned to the average level in HHcy animals supplemented with H 2 S. Interestingly, H 2 S supplementation ameliorated neurovascular remodeling and neurodegeneration. Thus, our study suggested that H 2 S could be a beneficial therapeutic candidate for the treatment of Hcy-associated neurodegeneration, such as stroke and neurovascular disorders.


Asunto(s)
Trastornos Cerebrovasculares/tratamiento farmacológico , Sulfuro de Hidrógeno/farmacología , Hiperhomocisteinemia/tratamiento farmacológico , Degeneración Nerviosa/tratamiento farmacológico , Animales , Barrera Hematoencefálica/efectos de los fármacos , Trastornos Cerebrovasculares/inducido químicamente , Trastornos Cerebrovasculares/metabolismo , Trastornos Cerebrovasculares/patología , Modelos Animales de Enfermedad , Homocisteína/toxicidad , Humanos , Hiperhomocisteinemia/genética , Hiperhomocisteinemia/metabolismo , Hiperhomocisteinemia/patología , Metaloproteinasa 9 de la Matriz/genética , Ratones , Degeneración Nerviosa/inducido químicamente , Degeneración Nerviosa/metabolismo , Degeneración Nerviosa/patología , Fármacos Neuroprotectores/farmacología , Estrés Oxidativo/efectos de los fármacos , Permeabilidad/efectos de los fármacos , Accidente Cerebrovascular/tratamiento farmacológico , Accidente Cerebrovascular/metabolismo , Accidente Cerebrovascular/patología
6.
AAPS PharmSciTech ; 20(5): 169, 2019 Apr 19.
Artículo en Inglés | MEDLINE | ID: mdl-31004249

RESUMEN

The aim of the present study was to explore the therapeutic efficacy of microemulsion-based delivery of histidine-capped silver nanoparticles in eradicating Klebsiella pneumoniae-induced burn wound infection. The developed microemulsion was characterized on the basis of differential light scattering, phase separation, refractive index, and specific conductance. Emulgel was prepared and characterized on the basis of thixotropy, texture, differential scanning calorimetry, and release kinetics. Emulgel was further evaluated in skin irritation and in vivo studies, namely full-thickness K. pneumoniae-induced burn wound infection treatment via topical route. Efficacy of treatment was evaluated in terms of bacterial load, histopathology, wound contraction, and other infection markers. The developed emulgel provided significant in vivo antibacterial activity of histidine-capped silver nanoparticle preparations via topical route and resulted in reduction in bacterial load, wound contraction, and enhanced skin healing as well as decrement of inflammatory markers such as malondialdehyde, myeloperoxidase, and reactive nitrogen intermediate compared to untreated animals. The present study encourages the further employment of histidine-capped silver nanoparticles along with microemulsion-based drug delivery system in combating antibiotic-resistant topical infections.


Asunto(s)
Antiinfecciosos Locales/administración & dosificación , Antiinfecciosos Locales/uso terapéutico , Quemaduras/complicaciones , Histidina/administración & dosificación , Histidina/uso terapéutico , Infecciones por Klebsiella/tratamiento farmacológico , Klebsiella pneumoniae , Compuestos de Plata/administración & dosificación , Compuestos de Plata/uso terapéutico , Infección de Heridas/tratamiento farmacológico , Administración Tópica , Animales , Sistemas de Liberación de Medicamentos , Emulsiones , Femenino , Geles , Infecciones por Klebsiella/microbiología , Nanopartículas del Metal , Ratones , Ratones Endogámicos BALB C , Nanopartículas/administración & dosificación , Nanopartículas/uso terapéutico , Infección de Heridas/microbiología
8.
Bioconjug Chem ; 29(4): 1102-1110, 2018 04 18.
Artículo en Inglés | MEDLINE | ID: mdl-29489340

RESUMEN

Peptide-based drug delivery systems have become a mainstay in the contemporary medicinal field, resulting in the design and development of better pharmaceutical formulations. However, most of the available reports employ tedious multiple reaction steps for the conjugation of bioactive cationic peptides with drug delivery vehicles. To overcome these limitations, the present work describes a one-step approach for facile and time efficient synthesis of highly cationic cell penetrating peptide functionalized gold nanoparticles and their intracellular delivery. The nanoconstruct was synthesized by the reduction of gold metal ions utilizing cell penetrating peptide (CPP), which facilitated the simultaneous synthesis of metal nanoparticles and the capping of the peptide over the nanoparticle surface. The developed nanoconstruct was thoroughly characterized and tested for intracellular delivery into HeLa cells. Intriguingly, a high payload of cationic peptide over gold particles was achieved, in comparison to conventional conjugation methods. Moreover, this method also provides the ability to control the size and peptide payload of nanoparticles. The nanoconstructs produced showed enhanced cancer cell penetration (µM) and significant cytotoxic effect compared to unlabeled gold nanoparticles. Therefore, this novel approach may also have significant future potential to kill intracellular hidden dreaded pathogens like the human immunodeficiency virus, Mycobacterium tuberculosis, and so forth.


Asunto(s)
Péptidos de Penetración Celular/administración & dosificación , Oro/química , Nanopartículas del Metal/química , Péptidos/síntesis química , Cationes , Proliferación Celular/efectos de los fármacos , Péptidos de Penetración Celular/química , Péptidos de Penetración Celular/farmacología , Coloides/química , Sistemas de Liberación de Medicamentos , Estabilidad de Medicamentos , Células HeLa , Humanos , Concentración de Iones de Hidrógeno , Péptidos/química , Temperatura , Agua
9.
Dermatol Ther ; 30(5)2017 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-28621443

RESUMEN

Keloids are developed as fibrotic scar at the site of surgery or trauma and often enlarge beyond the original scar margins. Re-188 colloid coated customized patch was superficially fixed onto the lesion for 3 hrs. The same patch was reapplied on the lesion on third day for 3 hrs. The patients were followed up at 1, 3,6 and 12 months post treatment. The size and elevation of the keloid lesion was reduced after treatment. The total radiation dose from the patch (day-1 and day-3) was 100 Gy/mCi of Re-188. The radioactive patch treatment of keloids is noninvasive, painless and safe with prolonged outcome.


Asunto(s)
Coloides/administración & dosificación , Queloide/terapia , Radioisótopos/administración & dosificación , Renio/administración & dosificación , Adulto , Anciano , Femenino , Estudios de Seguimiento , Humanos , Queloide/patología , Masculino , Persona de Mediana Edad , Factores de Tiempo , Parche Transdérmico , Resultado del Tratamiento , Adulto Joven
10.
Luminescence ; 30(6): 878-82, 2015 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-25620581

RESUMEN

Results on optically stimulated luminescence (OSL) in LiCaAlF6:Eu(2+) are reported. Continuous wave OSL signal as recorded using blue (470 nm) stimulation was found to be ~31% that of standard phosphor lithium magnesium phosphate. The rate of OSL depletion for standard phosphor lithium magnesium phosphate is only three times less as compared with that of LiCaAlF6:Eu(2+). Strong photoluminescence (PL) in the near ultraviolet region is observed for LiCaAlF6:Eu(2+) with the characteristic Eu(2+) emission at 369 nm for 254 nm excitation. The thermoluminescence (TL) glow peak for LiCaAlF6:Eu(2+) was observed at around 180°C. The glow peak was about six times more intense compared with the dosimetric peak of the well known thermoluminescence dosimetric (TLD) phosphor LiF-TLD 100. Thus this phosphor deserves much more attention than it has received until now and may be useful as a dosimetric material in radiation dosimetry.


Asunto(s)
Europio/química , Sustancias Luminiscentes/química , Partículas beta , Litio/química , Luminiscencia , Sustancias Luminiscentes/efectos de la radiación , Estroncio/química , Dosimetría Termoluminiscente/métodos , Difracción de Rayos X
11.
Proc Natl Acad Sci U S A ; 108(25): 10144-9, 2011 Jun 21.
Artículo en Inglés | MEDLINE | ID: mdl-21646541

RESUMEN

MicroRNA 21 (miR-21) is overexpressed in virtually all types of carcinomas and various types of hematological malignancies. To determine whether miR-21 promotes tumor development in vivo, we knocked out the miR-21 allele in mice. In response to the 7,12-dimethylbenz[a]anthracene (DMBA)/12-O-tetradecanoylphorbol-13-acetate mouse skin carcinogenesis protocol, miR-21-null mice showed a significant reduction in papilloma formation compared with wild-type mice. We revealed that cellular apoptosis was elevated and cell proliferation was decreased in mice deficient of miR-21 compared to wild-type animals. In addition, we found that a large number of validated or predicted miR-21 target genes were up-regulated in miR-21-null keratinocytes, which are precursor cells to skin papillomas. Specifically, up-regulation of Spry1, Pten, and Pdcd4 when miR-21 was ablated coincided with reduced phosphorylation of ERK, AKT, and JNK, three major downstream effectors of Ras activation that plays a predominant role in DMBA-initiated skin carcinogenesis. These results provide in vivo evidence that miR-21 exerts its oncogenic function through negatively regulating its target genes.


Asunto(s)
Transformación Celular Neoplásica/genética , Regulación Neoplásica de la Expresión Génica , MicroARNs/metabolismo , 9,10-Dimetil-1,2-benzantraceno/farmacología , Animales , Apoptosis/genética , Carcinógenos/farmacología , Proliferación Celular , Células Epidérmicas , Epidermis/efectos de los fármacos , Epidermis/patología , Epidermis/fisiología , Femenino , Queratinocitos/citología , Queratinocitos/efectos de los fármacos , Queratinocitos/fisiología , Ratones , Ratones Noqueados , MicroARNs/genética , Transducción de Señal/fisiología , Neoplasias Cutáneas/inducido químicamente , Neoplasias Cutáneas/patología , Neoplasias Cutáneas/fisiopatología , Acetato de Tetradecanoilforbol/farmacología , Proteínas ras/genética , Proteínas ras/metabolismo
12.
J Cancer Res Ther ; 20(1): 289-296, 2024 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-38554336

RESUMEN

PURPOSE: Majority of the gallbladder cancer (GBC) cases are diagnosed at an advanced stage where chemotherapy alone (or in combination with other treatment methods) is mainly opted as therapeutic approach. However, success or failure of this approach largely depends on the interindividual genetic differences. Careful consideration on the genetic association could assist in the evaluation of patient's treatment response and survival rate. Hence, the present study aims to investigate the survival of patients with GBC and their treatment response to gemcitabine and cisplatin/carboplatin-based chemotherapy in association with Glutathione S-transferase (GSTs) gene polymorphism. MATERIAL AND METHODS: A total of 216 histologically confirmed cases of gallbladder cancer were recruited. A total of 180 patients were treated with gemcitabine and cisplatin/carboplatin-based chemotherapy. GSTM1, GSTT1, and GSTP1 genotypes were determined by multiplex PCR and by PCR restriction fragment length polymorphism (PCR-RFLP), respectively. The influence of genetic polymorphism on overall survival was analyzed by Kaplan-Meier method, survival rate difference was analyzed by log-rank test, and hazard ratio for mortality outcomes was estimated using Cox regression method. RESULTS: GBC patients having genotype GSTP1 (AG + GG) showed poor 3-year survival rate of 0.8% compared to 10.9% of GSTP1 (AA) genotype (χ2 = 6.456, P = 0.011). The multivariate Cox regression results showed that the death risk was significantly higher in GSTP1 (AG + GG) genotype (HR = 3.858, P = 0.050). We found no association of GSTM1 and GSTT1 gene polymorphism with the survival; however, the combined genotypes of GSM1/GSTP1, GSTT1/GSTP1, and GSTM1/GSTT1/GSTP1 were associated with survival (P = 0.053, 0.006, and 0.058, respectively). Increased death hazard was noted by the genotype combinations of GSTM1+/GSTP1AG + GG (HR = 3.484, P = 0.024), GSTM1-/GSTP1AG + GG (HR = 2.721, P = 0.014), GSTT1+/GSTP1AG + GG (HR = 20.690, P = 0.001), and GSTT1-/GSTP1AA (HR = 26.111, P < 0.0001). Our findings indicate that chemotherapy treatment response of GSTP1 (AG + GG) has 1.62-fold increased risk for progression compared to GSTP1 (AA) genotype (p = 0.018); however, none of the genotypes showed association with overall survival and death risk after chemotherapeutic treatment. CONCLUSION: We found that the presence of GSTP1 (AG + GG) genotype showed survival disadvantage and poor treatment outcomes in response to gemcitabine and cisplatin/carboplatin-based chemotherapy. This could serve as biomarker, and future research in pharmacogenomics will definitely pave the way for the development of better treatment approach for GBC.


Asunto(s)
Cisplatino , Neoplasias de la Vesícula Biliar , Humanos , Cisplatino/uso terapéutico , Carboplatino , Gemcitabina , Neoplasias de la Vesícula Biliar/tratamiento farmacológico , Neoplasias de la Vesícula Biliar/genética , Predisposición Genética a la Enfermedad , Polimorfismo Genético , Glutatión Transferasa/genética , Gutatión-S-Transferasa pi/genética , Genotipo , Análisis de Supervivencia , Resultado del Tratamiento
13.
Cells ; 13(10)2024 May 17.
Artículo en Inglés | MEDLINE | ID: mdl-38786076

RESUMEN

Cardiovascular diseases continue to challenge global health, demanding innovative therapeutic solutions. This review delves into the transformative role of mesenchymal stem cells (MSCs) in advancing cardiovascular therapeutics. Beginning with a historical perspective, we trace the development of stem cell research related to cardiovascular diseases, highlighting foundational therapeutic approaches and the evolution of cell-based treatments. Recognizing the inherent challenges of MSC-based cardiovascular therapeutics, which range from understanding the pro-reparative activity of MSCs to tailoring patient-specific treatments, we emphasize the need to refine the pro-regenerative capacity of these cells. Crucially, our focus then shifts to the strategies of the fourth generation of cell-based therapies: leveraging the secretomic prowess of MSCs, particularly the role of extracellular vesicles; integrating biocompatible scaffolds and artificial sheets to amplify MSCs' potential; adopting three-dimensional ex vivo propagation tailored to specific tissue niches; harnessing the promise of genetic modifications for targeted tissue repair; and institutionalizing good manufacturing practice protocols to ensure therapeutic safety and efficacy. We conclude with reflections on these advancements, envisaging a future landscape redefined by MSCs in cardiovascular regeneration. This review offers both a consolidation of our current understanding and a view toward imminent therapeutic horizons.


Asunto(s)
Enfermedades Cardiovasculares , Trasplante de Células Madre Mesenquimatosas , Células Madre Mesenquimatosas , Humanos , Células Madre Mesenquimatosas/citología , Enfermedades Cardiovasculares/terapia , Trasplante de Células Madre Mesenquimatosas/métodos , Animales , Vesículas Extracelulares/metabolismo , Vesículas Extracelulares/trasplante , Tratamiento Basado en Trasplante de Células y Tejidos/métodos
14.
OMICS ; 28(5): 234-245, 2024 05.
Artículo en Inglés | MEDLINE | ID: mdl-38717843

RESUMEN

Cerebral vasospasm (CV) is a significant complication following aneurysmal subarachnoid hemorrhage (aSAH), and lacks a comprehensive molecular understanding. Given the temporal trajectory of intracranial aneurysm (IA) formation, its rupture, and development of CV, altered gene expression might be a molecular substrate that runs through these clinical events, influencing both disease inception and progression. Utilizing RNA-Seq, we analyzed tissue samples from ruptured IAs with and without vasospasm to identify the dysregulated genes. In addition, temporal gene expression analysis was conducted. We identified seven dysregulated genes in patients with ruptured IA with vasospasm when compared with those without vasospasm. We found 192 common genes when the samples of each clinical subset of patients with IA, that is, unruptured aneurysm, ruptured aneurysm without vasospasm, and ruptured aneurysm with vasospasm, were compared with control samples. Among these common genes, TNFSF13B, PLAUR, OSM, and LAMB3 displayed temporal expression (progressive increase) with the pathological progression of disease that is formation of aneurysm, its rupture, and consequently the development of vasospasm. We validated the temporal gene expression pattern of OSM at both the transcript and protein levels and OSM emerges as a crucial gene implicated in the pathological progression of disease. In addition, RSAD2 and ATP1A2 appear to be pivotal genes for CV development. To the best of our knowledge, this is the first study to compare the transcriptome of aneurysmal tissue samples of aSAH patients with and without CV. The findings collectively provide new insights on the molecular basis of IA and CV and new leads for translational research.


Asunto(s)
Perfilación de la Expresión Génica , Aneurisma Intracraneal , Transcriptoma , Vasoespasmo Intracraneal , Humanos , Vasoespasmo Intracraneal/genética , Vasoespasmo Intracraneal/metabolismo , Aneurisma Intracraneal/genética , Aneurisma Intracraneal/metabolismo , Aneurisma Intracraneal/complicaciones , Transcriptoma/genética , Perfilación de la Expresión Génica/métodos , Masculino , Femenino , Hemorragia Subaracnoidea/genética , Hemorragia Subaracnoidea/complicaciones , Hemorragia Subaracnoidea/metabolismo , Regulación de la Expresión Génica , Persona de Mediana Edad , Aneurisma Roto/genética , Aneurisma Roto/complicaciones
15.
J Mol Neurosci ; 74(1): 18, 2024 Feb 05.
Artículo en Inglés | MEDLINE | ID: mdl-38315311

RESUMEN

Delayed cerebral ischemia (DCI) is one of the major causes of a poor neurological outcome following aneurysmal subarachnoid hemorrhage (aSAH). Several biomarkers, including matrix metalloproteinase-9 (MMP-9), have been evaluated to predict the development of DCI for timely management. This prospective cohort study was done on 98 patients with aSAH presenting within 72 h of the ictus. Serum samples were collected preoperatively, 7 days after ictus, 10 days after ictus, or when the patient developed DCI, whichever was earlier. The primary objective was to correlate the serum MMP-9 levels with the development of DCI. The secondary objectives were to correlate the serum MMP-9 levels with sonographic vasospasm and the neurological outcome. There was no correlation between the serum MMP-9 levels and the development of DCI (p = 0.37). Similarly, there was no correlation between the serum MMP-9 levels and the sonographic vasospasm (0.05) nor with the modified Rankin Scale (mRS) at discharge (p = 0.27), mRS at 3 months (p = 0.22), and Glasgow Outcome Scale Extended (GOSE) at 3 months (p = 0.15). Serum MMP-9 levels do not predict the development of DCI following aSAH.


Asunto(s)
Isquemia Encefálica , Hemorragia Subaracnoidea , Humanos , Hemorragia Subaracnoidea/complicaciones , Metaloproteinasa 9 de la Matriz , Estudios Prospectivos , Infarto Cerebral
16.
Pharm Biol ; 51(2): 233-9, 2013 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-23127163

RESUMEN

CONTEXT: Butea frondosa (BF) Roxb. & Koen. (syn. B. monosperma Lam.) (Fabaceae) leaves have been used in folklore medicine for the treatment of diabetes, conjunctivitis, gastrointestinal tract, and central nervous system disorders such as anxiety, amnesia, etc. OBJECTIVE: To evaluate the effect of lyophilized hydroalcoholic extract of BF leaves (BFLE) at 100, 200 and 400 mg/kg, p.o., for its memory enhancing activity against scopolamine-induced amnesia in rats. MATERIALS AND METHODS: Antiamnesic effect of the BFLE was evaluated using Morris water maze and object recognition test models. The effect of BFLE on acetylcholinesterase activity and malondialdehyde and glutathione levels were also evaluated in brain homogenate. RESULT: BFLE ameliorates scopolamine-induced amnesia in both the models with maximum effect at 400 mg/kg. BFLE (400 mg/kg) decreased escape latency and increased time spent in target quadrant (24.2 and 42.5 s, respectively) in comparison to scopolamine (82 and 18.2 s, respectively) in the Morris water maze task. In the object recognition test, BFLE produced significant increase in ability to discriminate between novel and familiar objects. The highest investigated dose of BFLE (400 mg/kg), produced a significant decrease in acetylcholinesterase activity and malondialdehyde levels, and improves glutathione levels in comparison to scopolamine. Moreover, this effect of BFLE at 400 mg/kg was comparable to that of standard, donepezil. CONCLUSION: BFLE exhibited significant antiamnesic activity in rats thereby validating its folklore use.


Asunto(s)
Amnesia/tratamiento farmacológico , Conducta Animal/efectos de los fármacos , Encéfalo/efectos de los fármacos , Butea/química , Liofilización , Memoria/efectos de los fármacos , Nootrópicos/farmacología , Extractos Vegetales/farmacología , Escopolamina , Acetilcolinesterasa/metabolismo , Administración Oral , Amnesia/inducido químicamente , Amnesia/metabolismo , Amnesia/psicología , Animales , Antioxidantes/farmacología , Encéfalo/metabolismo , Inhibidores de la Colinesterasa/farmacología , Discriminación en Psicología/efectos de los fármacos , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Reacción de Fuga/efectos de los fármacos , Femenino , Proteínas Ligadas a GPI/antagonistas & inhibidores , Proteínas Ligadas a GPI/metabolismo , Glutatión/metabolismo , Masculino , Malondialdehído/metabolismo , Aprendizaje por Laberinto/efectos de los fármacos , Nootrópicos/administración & dosificación , Nootrópicos/aislamiento & purificación , Extractos Vegetales/administración & dosificación , Extractos Vegetales/aislamiento & purificación , Hojas de la Planta , Plantas Medicinales , Ratas , Ratas Wistar , Tiempo de Reacción/efectos de los fármacos , Reconocimiento en Psicología/efectos de los fármacos , Factores de Tiempo
17.
J Ambient Intell Humaniz Comput ; 14(4): 3609-3620, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-34548886

RESUMEN

Image classification is getting more attention in the area of computer vision. During the past few years, a lot of research has been done on image classification using classical machine learning and deep learning techniques. Presently, deep learning-based techniques have given stupendous results. The performance of a classification system depends on the quality of features extracted from an image. The better is the quality of extracted features, the more the accuracy will be. Although, numerous deep learning-based methods have shown enormous performance in image classification, still due to various challenges deep learning methods are not able to extract all the important information from the image. This results in a reduction in overall classification accuracy. The goal of the present research is to improve the image classification performance by combining the deep features extracted using popular deep convolutional neural network, VGG19, and various handcrafted feature extraction methods, i.e., SIFT, SURF, ORB, and Shi-Tomasi corner detector algorithm. Further, the extracted features from these methods are classified using various machine learning classification methods, i.e., Gaussian Naïve Bayes, Decision Tree, Random Forest, and eXtreme Gradient Boosting (XGBClassifier) classifier. The experiment is carried out on a benchmark dataset Caltech-101. The experimental results indicate that Random Forest using the combined features give 93.73% accuracy and outperforms other classifiers and methods proposed by other authors. The paper concludes that a single feature extractor whether shallow or deep is not enough to achieve satisfactory results. So, a combined approach using deep learning features and traditional handcrafted features is better for image classification.

18.
J Cancer Res Ther ; 19(7): 1908-1914, 2023 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-38376296

RESUMEN

AIM: In the present case-controlled study, we explored the role of genetic polymorphism in three xenobiotic metabolizing genes, GSTM1, GSTT1 and GSTP1, and their association to gallbladder cancer (GBC) risk in a North Indian population. Its etiology is influenced by genetic, food habits, lifestyle, and environmental factors. GBC incidence is significantly higher in the Gangetic belt, India. Therefore, we explored the prognostic factors in the susceptibility of GBC through gene-gene and gene-environment interaction in this region. MATERIAL AND METHODS: Genetic polymorphism was analyzed in 108 GBC patients from Kamala Nehru Memorial Cancer Hospital, Prayagraj and 142 matched controls. GSTM1 and GSTT1 genotypes were analyzed by multiplex PCR method, while restriction fragment length polymorphism (RFLP) was performed to analyze GSTP1 genotypes. Logistic regression analysis calculating the odds ratio (OR) and 95% confidence interval (CI) was performed to analyze the GBC risk. RESULTS: GSTT1 (null) genotype was at a significantly higher risk and susceptible to GBC (OR = 2.044, CI = 1.225-3.411, P = 0.006), while GSTM1 and GSTP1 genotypes did not show any association to GBC risk. After sex stratification, females diagnosed with GBC had higher GSTT1 (null) genotype (OR = 2.754, CI = 1.428-5.310, P = 0.003) compared to males. GBC patients dwelling in rural areas show higher GSTT1 (null) genotype with two-fold GBC risk (OR = 2.031, CI = 1.200-3.439, P = 0.008). Further, GBC patients with histopathology of adenocarcinoma also showed higher GSTT1 (null) genotype (OR = 2.113, CI = 1.248-3.578, P = 0.005). Gene-gene interaction between GSTT1 (non-null)/GSTP1 (Ile/Val + Val/Val), enhance the GBC risk (OR = 1.840, CI = 1.135-2.982, P = 0.013). CONCLUSIONS: The present study suggests that GSTT1 (null) genotype has higher susceptibility and risk towards GBC in North Indian population. Female patients, patients with histopathology of adenocarcinoma and rural dwelling GBC patients have higher GSTT1 (null) genotypes and may be at risk of developing GBC. The genotype combination GSTT1 (non-null)/GSTP1 (Ile/Val + Val/Val) has increased GBC susceptibility and may be considered as 'at risk' genotypes for GBC in North Indians.


Asunto(s)
Adenocarcinoma , Neoplasias de la Vesícula Biliar , Glutatión Transferasa , Femenino , Humanos , Masculino , Neoplasias de la Vesícula Biliar/epidemiología , Neoplasias de la Vesícula Biliar/genética , Interacción Gen-Ambiente , Genotipo , Polimorfismo Genético , Estudios de Casos y Controles , Glutatión Transferasa/genética
19.
Cureus ; 15(7): e41465, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-37546075

RESUMEN

Parry-Romberg syndrome (PRS) is a rare degenerative disorder of unknown cause that causes slow, progressive atrophy on one side of the face. The cause may be a malfunction of the sympathetic nervous system, with or without neurological symptoms. Atrophy usually begins in childhood and progresses gradually over several years. Stabilization can take up to 20 years. There is no definitive cure for this condition, but once the condition is stabilized, reconstructive surgery of the damaged skin and soft tissue can correct the deformity. The objective of this article is to present an insight into the etiology of PRS with a case report of a 15-year-old male patient, who was diagnosed with PRS due to trauma and developed progressive hemifacial atrophy without neurological manifestations. PRS is a progressive disease that severely affects one side of the face. Because of its devastating effects on the entire body, treatment requires a multidisciplinary approach. Further research is needed to clearly understand the etiology and provide patients with accurate treatment plans.

20.
Multimed Tools Appl ; 82(5): 7553-7566, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36060226

RESUMEN

As of March 31, 2021, the Coronavirus COVID-19 was affecting 219 countries and territories worldwide, with approximately 129,574,017 confirmed cases and 2,830,220 death cases. Social isolation is the most reliable way to deal with this pandemic situation. Motivated by this notion, this paper proposes a deep learning-based technique for automating the task of monitoring social distancing using surveillance cameras. To separate humans from the background, the proposed system employs object detection models based on F-RCNN (Faster Region-based Convolutional Neural Networks) and YOLO (You Only Look Once) algorithms. In the COVID-19 environment, these models track the percentage of people who violate social distancing norms on a daily basis. The authors compared the performance of both models in experimental work using the MS COCO dataset. Many tests were carried out, and we discovered that YOLOv3 demonstrated efficient performance with balanced FPS (frames per second).

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