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Transcatheter aortic valve replacement by alternate access sites allows for treatment of patients with unfavorable anatomy for a transfemoral approach. To our knowledge, we present the first reported case of successful transcatheter aortic valve replacement via the transcarotid approach in a 65-year-old man with a symptomatic severe bicuspid aortic valve stenosis and virtually atretic coarctation of the thoracic aorta.
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PURPOSE: To assess outcomes of keratoplasty performed in patients diagnosed with keratitis caused by Pythium insidiosum (PI). DESIGN: Retrospective review. METHODS: Preoperative, intra operative and post operative data of patients diagnosed with PI keratitis and who underwent keratoplasty for their condition from January 2020 to December 2021 were collected from the central patient database of a tertiary eye care hospital in India. The data were analyzed for anatomic success, elimination of infection, graft survival, incidence of repeat keratoplasty, final visual acuity and varied complications. RESULTS: In total, 16 eyes underwent penetrating keratoplasty for PI keratitis during the study period. Mean time to keratoplasty from onset of symptoms was 31.3 days and mean graft size was 10.4 mm. Nine out of the 16 cases had recurrence of infection following surgery, seven of which required a repeat keratoplasty for elimination of infection. Mean graft size for repeat keratoplasty performed in recurrent cases was 11.7 mm. Globe was successfully salvaged in 14 out of 16 patients (87.5 %). Three grafts remained clear at 6-month follow up while 11 grafts failed. Mean improvement in uncorrected visual acuity from 2.32 to 2.04 logMAR was observed at last follow up. Endo-exudates, graft infiltration, graft dehiscence, secondary glaucoma and retinal detachment were the various complications noted after keratoplasty. CONCLUSION: PI keratitis is a tenacious and potentially blinding condition. Keratoplasty remains the choice of treatment in this condition, however recurrence of disease and graft failure are common. Large sized grafts, meticulous per-operative removal of infection, adjuvant cryotherapy, and intraoperative and post operative use of antibiotics can help in improving outcome of keratoplasty in these patients.
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Queratoplastia Penetrante , Pitiosis , Centros de Atención Terciaria , Agudeza Visual , Humanos , India/epidemiología , Estudios Retrospectivos , Masculino , Femenino , Adulto , Queratoplastia Penetrante/métodos , Persona de Mediana Edad , Pitiosis/diagnóstico , Pitiosis/cirugía , Queratitis/diagnóstico , Queratitis/cirugía , Queratitis/microbiología , Queratitis/epidemiología , Supervivencia de Injerto , Estudios de Seguimiento , Pythium/aislamiento & purificación , Adulto Joven , Córnea/cirugía , Córnea/patología , Córnea/parasitología , Córnea/microbiología , Resultado del Tratamiento , Anciano , Infecciones Parasitarias del Ojo/cirugía , Infecciones Parasitarias del Ojo/diagnóstico , Infecciones Parasitarias del Ojo/parasitología , Infecciones Parasitarias del Ojo/epidemiología , AdolescenteRESUMEN
Prone positioning of patients is a routine occurrence in procedural suites and operating rooms (ORs). However, the physiological changes that occur with prone positioning are frequently underappreciated by proceduralists, surgeons, and anesthesiologists. This may be related to a sense of the routine or a lack of familiarity with physiological changes that accompany the prone position. The prone position, while aiding visualization and cannulation of the ampulla of Vater during endoscopic retrograde cholangiopancreatography (ERCP), can induce physiological changes such as reduced preload, inferior vena cava filling, and cardiac output; it can also increase intrathoracic pressure and mediastinal compression. Anesthetic agents can further impact cardiopulmonary physiology, decreasing systemic vascular resistance and reducing cardiac contractility. In addition, the transition from negative to positive pressure ventilation following endotracheal intubation can increase pulmonary artery pressures and right ventricular (RV) strain. Therefore, caution is needed with patients who have RV dysfunction, pulmonary hypertension, or preload dependency, as they may not tolerate prone positioning. We describe a case in which a 73-year-old male patient scheduled for an ERCP suffered cardiac arrest after being transitioned to the prone position. The patient was repositioned in the supine position and resuscitated. The case was completed in the supine position.
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Cornea-related injuries are the most common cause of blindness worldwide. Transplantation remains the primary approach for addressing corneal blindness, though the demand for donor corneas outmatches the supply by millions. Tissue adhesives employed to seal corneal wounds have shown inefficient healing and incomplete vision restoration. We have developed a biodegradable hydrogel - Kuragel, with the ability to promote corneal regeneration. Functionalized gelatin and hyaluronic acid form photo-crosslinkable hydrogel with transparency and compressive modulus similar to healthy human cornea. Kuragel composition was tuned to achieve sufficient adhesive strength for sutureless integration to host tissue, with minimal swelling post-administration. Studies in the New Zealand rabbit mechanical injury model affecting corneal epithelium and stroma demonstrate that Kuragel efficiently promotes re-epithelialization within 1 month of administration, while stroma and sub-basal nerve plexus regenerate within 3 months. We propose Kuragel as a regenerative treatment for patients suffering from corneal defects including thinning, by restoration of transparency and thickness.
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PURPOSE: Chemical eye injury is an acute emergency that can result in vision loss. Neurotrophic keratitis (NK) is the most common long-term manifestation of chemical injury. NK due to alkali burn affects ocular surface health and is one of its most common causes. Here, we established a rabbit model of corneal alkali burns to evaluate the severity of NK-associated changes. MATERIAL METHODS: Alkali burns were induced in NZ rabbits by treating the cornea with (i) a 5 mm circular filter paper soaked in 0.75 N NaOH for 10 s (Mild NK) and (ii) trephination using a guarded trephine (5 mm diameter and 150-micron depth), followed by alkali burn, with a 5 mm circular filter paper soaked in 0.75 N NaOH for 10 s (a severe form of NK). Immediately after, the cornea was rinsed with 10 mL of normal saline to remove traces of NaOH. Clinical features were evaluated on Day 0, Day 1, Day 7, Day 15, and Day 21 post-alkali burn using a slit lamp, Pentacam, and anterior segment optical coherence tomography (AS-OCT). NK-like changes in epithelium, sub-basal nerve plexus, and stroma were observed using in vivo confocal microscopy (IVCM), and corneal sensation were measured using an aesthesiometer post alkali injury. After 21 days, pro-inflammatory cytokines were evaluated for inflammation through ELISA. RESULTS: Trephination followed by alkali burn resulted in the loss of epithelial layers (manifested using fluorescein stain), extensive edema, and increased corneal thickness (550 µm compared to 380 µm thickness of control) evaluated through AS-OCT and increased opacity score in alkali-treated rabbit (80 compared to 16 controls). IVCM images showed complete loss of nerve fibers, which failed to regenerate over 30 days, and loss of corneal sensation-conditions associated with NK. Cytokines evaluation of IL6, VEGF, and MMP9 indicated an increased angiogenic and pro-inflammatory milieu compared to the milder form of NK and the control. DISCUSSION: Using clinical parameters, we demonstrated that the alkali-treated rabbit model depicts features of NK. Using IVCM in the NaOH burn animal model, we demonstrated a complete loss of nerve fibers with poor self-healing capability associated with sub-basal nerve degeneration and compromised corneal sensation. This pre-clinical rabbit model has implications for future pre-clinical research in neurotrophic keratitis.
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Quemaduras Químicas , Enfermedades de la Córnea , Queratitis , Conejos , Animales , Quemaduras Químicas/tratamiento farmacológico , Álcalis , Hidróxido de Sodio/uso terapéutico , Córnea , Microscopía Confocal/métodos , CitocinasRESUMEN
HSV1 presents as epithelial or stromal keratitis or keratouveitis and can lead to sight-threatening complications. KLF4, a critical transcription factor, and regulator of cell growth and differentiation, is essential in corneal epithelium stratification and homeostasis. Here, we want to understand the epigenetic modification specifically the methylation status of KLF4 in epithelium samples of HSV1 keratitis patients. After obtaining consent, epithelial scrapes were collected from 7 patients with clinically diagnosed HSV1 keratitis and 7 control samples (patients undergoing photorefractive keratectomy). Genomic DNA was isolated from the collected samples using the Qiagen DNeasy Kit. Subsequently, bisulfite modification was performed. The bisulphite-modified DNA was then subjected to PCR amplification using specific primers designed to target the KLF4, ACTB gene region, allowing for the amplification of methylated and unmethylated DNA sequences. The amplified DNA products were separated and visualized on a 3% agarose gel. KLF4 hypermethylation was found in 6 out of 7 (85.71%) eyes with viral keratitis, while 1 eye showed hypomethylation compared to PRK samples. Out of these 6, there were 2 each of epithelial dendritic keratitis, epithelial geographical keratitis, and neurotrophic keratitis. The patient with hypomethylated KLF4 had a recurrent case of HSV1 keratitis with multiple dendrites and associated vesicular lesions of the lip along with a history of fever. KLF4 hypermethylation in most viral keratitis cases indicated the under functioning of KLF4 and could indicate a potential association between KLF4 hypermethylation and the development or progression of HSV1 keratitis.
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Epitelio Corneal , Infecciones Virales del Ojo , Queratitis , Humanos , ADN , Metilación de ADN , Epitelio Corneal/patología , Infecciones Virales del Ojo/genética , Infecciones Virales del Ojo/patología , Queratitis/patologíaRESUMEN
Tears contain numerous secreted factors, enzymes, and proteins that help in maintaining the homeostatic condition of the eye and also protect it from the external environment. However, alterations to these enzymes and/or proteins during pathologies such as mechanical injury and viral or fungal infections can disrupt the normal ocular homeostasis, further contributing to disease development. Several tear film components have a significant role in curbing disease progression and promoting corneal regeneration. Additionally, several factors related to disease progression are secreted into the tear film, thereby serving as a valuable reservoir of biomarkers. Tears are readily available and can be collected via non-invasive techniques or simply from contact lenses. Tears can thus serve as a valuable and easy source for studying disease-specific biomarkers. Significant advancements have been made in recent years in the field of tear film proteomics, lipidomics, and transcriptomics to allow a better understanding of how tears can be utilized to gain insight into the etiology of diseases. These advancements have enabled us to study the pathophysiology of various disease states using tear samples. However, the mechanisms by which tears help to maintain corneal homeostasis and how they are able to form the first line of defense against pathogens remain poorly understood and warrant detailed in vitro studies. Herein, we have developed an in vitro assay to characterize the functional importance of patient isolated tears and their components on corneal epithelial cells. This novel approach closely mimics real physiological conditions and could help the researchers gain insight into the underlying mechanisms of ocular pathologies and develop new treatments. Key features ⢠This method provides a new technique for analyzing the effect of tear components on human corneal epithelial cells. ⢠The components of the tears that are altered in response to diseases can be used as a biomarker for detecting ocular complications. ⢠This procedure can be further employed as an in vitro model for assessing the efficacy of drugs and discover potential therapeutic interventions.
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BACKGROUND: Epilepsy is a neurological illness affecting the brain that makes people more likely to experience frequent, spontaneous seizures. There has to be an accurate automated method for measuring seizures frequency and severity to assess the efficacy of pharmacological therapy for epilepsy. The drug quantities are often derived from patient reports which may cause significant issues owing to inadequate or inaccurate descriptions of seizures and their frequencies. METHODS AND MATERIALS: This study proposes a novel deep learning architecture-based Lightweight Convolution Transformer (LCT). The Transformer model is able to learn spatial and temporal correlated information simultaneously from the multi-channel electroencephalogram (EEG) signal to detect seizures at smaller segment lengths. In the proposed work, the lack of translation equivariance and localization of ViT is reduced using convolution tokenization, and rich information from the Transformer encoder is extracted by sequence pooling instead of the learnable class token. RESULTS: Extensive experimental results demonstrate that the proposed model on cross-patient learning can effectively detect seizures from the raw EEG signals. The accuracy and F1-score of seizure detection in the cross-patient case on the CHB-MIT dataset are 96.31% and 96.32%, respectively, at 0.5 sec segment length. In addition, the performance metrics show that the inclusion of inductive biases and attention-based pooling in the model enhances the performance and reduces the number of Transformer encoder layers, which significantly reduces the computational complexity. In this research, we provide a novel approach to enhance efficiency and simplify the architecture for multi-channel automated seizure detection.
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Epilepsia , Convulsiones , Humanos , Convulsiones/diagnóstico , Epilepsia/diagnóstico , Electroencefalografía/métodos , EncéfaloRESUMEN
Retinoblastoma is a retinal cancer that affects children and is the most prevalent intraocular tumor worldwide. Despite tremendous breakthroughs in our understanding of the fundamental mechanisms that regulate progression of retinoblastoma, the development of targeted therapeutics for retinoblastoma has lagged. Our review highlights the current developments in the genetic, epigenetic, transcriptomic, and proteomic landscapes of retinoblastoma. We also discuss their clinical relevance and potential implications for future therapeutic development, with the aim to create a frontline multimodal therapy for retinoblastoma.
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Neoplasias de la Retina , Retinoblastoma , Niño , Humanos , Retinoblastoma/tratamiento farmacológico , Retinoblastoma/genética , Proteómica , Neoplasias de la Retina/diagnóstico , Neoplasias de la Retina/tratamiento farmacológico , Neoplasias de la Retina/genética , Terapia CombinadaRESUMEN
Hypertensive Retinopathy (HR) is a retinal disease caused by elevated blood pressure for a prolonged period. There are no obvious signs in the early stages of high blood pressure, but it affects various body parts over time, including the eyes. HR is a biomarker for several illnesses, including retinal diseases, atherosclerosis, strokes, kidney disease, and cardiovascular risks. Early microcirculation abnormalities in chronic diseases can be diagnosed through retinal examination prior to the onset of major clinical consequences. Computer-aided diagnosis (CAD) plays a vital role in the early identification of HR with improved diagnostic accuracy, which is time-efficient and demands fewer resources. Recently, numerous studies have been reported on the automatic identification of HR. This paper provides a comprehensive review of the automated tasks of Artery-Vein (A/V) classification, Arteriovenous ratio (AVR) computation, HR detection (Binary classification), and HR severity grading. The review is conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocol. The paper discusses the clinical features of HR, the availability of datasets, existing methods used for A/V classification, AVR computation, HR detection, and severity grading, and performance evaluation metrics. The reviewed articles are summarized with classifiers details, adoption of different kinds of methodologies, performance comparisons, datasets details, their pros and cons, and computational platform. For each task, a summary and critical in-depth analysis are provided, as well as common research issues and challenges in the existing studies. Finally, the paper proposes future research directions to overcome challenges associated with data set availability, HR detection, and severity grading.
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Retinopatía Hipertensiva , Enfermedades de la Retina , Humanos , Fondo de Ojo , Interpretación de Imagen Asistida por Computador/métodos , Retinopatía Hipertensiva/diagnóstico , Diagnóstico por Computador/métodos , Enfermedades de la Retina/diagnóstico , ComputadoresRESUMEN
Introduction: Road Traffic Accidents, are one of the major neglected global health burdens which are predicted to be the 7th leading cause of global deaths by 2030 as per the World Health Organization hence, seem to be one of the major global threats in near future. Most road traffic accidents affect the most vulnerable age groups in developing countries. The aim of this study was to find out the prevalence of road traffic accidents among patients visiting the Department of Emergency of a tertiary care centre. Methods: A descriptive cross-sectional study was conducted among patients visiting the department of emergency of a tertiary care centre from 16 September 2022 to 15 October 2022. Ethical approval was obtained from the Institutional Review Committee (Reference number: IRC-DMCRI: 307/079/080). All the road traffic accidents cases recorded in the Emergency Department from 14 April 2021 to 13 April 2022 were taken. Convenience sampling was used. Point estimate and 95% confidence interval were calculated. Results: Among 29735 patients, the prevalence of road traffic accidents was 1340 (4.50%) (4.26-4.74, 95% Confidence Interval). Among these, 1037 (77.4%) were male and 303 (22.6%) were female. Road traffic accidents among two-wheelers were 1065 (79.48%) followed by pedestrian 703 (52.46%). Mangsir witness the higher number of cases, 137 (13.90%) followed by Kartik, 170 (12.69%). Conclusions: The prevalence of road traffic accidents was similar to other studies done in similar settings. In our study, young people of highly productive and active age groups were the most common victims. Keywords: emergencies; prevalence; traffic accidents.
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Accidentes de Tránsito , Servicio de Urgencia en Hospital , Humanos , Masculino , Femenino , Adolescente , Centros de Atención Terciaria , Estudios Transversales , PrevalenciaRESUMEN
INTRODUCTION: Artificial intelligence (AI) technology has transformed the way healthcare functions in the present scenario. In orthodontics, expert systems and machine learning have aided clinicians in making complex, multifactorial decisions. One such scenario is an extraction decision in a borderline case. OBJECTIVE: The present in silico study was planned with the intention of building an AI model for extraction decisions in borderline orthodontic cases. DESIGN: An observational analytical study. SETTING: Department of Orthodontics, Hitkarini Dental College and Hospital, Madhya Pradesh Medical University, Jabalpur, India. METHODS: An artificial neural network (ANN) model for extraction or non-extraction decisions in borderline orthodontic cases was constructed based on a supervised learning algorithm using the Python (version 3.9) Sci-Kit Learn library and feed-forward backpropagation method. Based on 40 borderline orthodontic cases, 20 experienced clinicians were asked to recommend extraction or non-extraction treatment. The decision of the orthodontist and the diagnostic records, including the selected extraoral and intra-oral features, model analysis and cephalometric analysis parameters, constituted the training dataset of AI. The built-in model was then tested using a testing dataset of 20 borderline cases. After running the model on the testing dataset, the accuracy, F1 score, precision and recall were calculated. RESULTS: The present AI model showed an accuracy of 97.97% for extraction and non-extraction decision-making. The receiver operating curve (ROC) and cumulative accuracy profile showed a near-perfect model with precision, recall and F1 values of 0.80, 0.84 and 0.82 for non-extraction decisions and 0.90, 0.87 and 0.88 for extraction decisions. LIMITATION: As the present study was preliminary in nature, the dataset included was too small and population-specific. CONCLUSION: The present AI model gave accurate results in decision-making capabilities related to extraction and non-extraction treatment modalities in borderline orthodontic cases of the present population.
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Inteligencia Artificial , Ortodoncia , Humanos , Algoritmos , Redes Neurales de la Computación , OrtodoncistasRESUMEN
INTRODUCTION: Treating a Class III malocclusion is often challenging for orthodontists. Bone-anchored maxillary protraction (BAMP) is known for achieving a significant maxillary protraction. The study aimed to evaluate the stress distribution and displacement of craniofacial bones as a reaction to the forces of BAMP, along with rapid maxillary expander and the posterior bite plane, in growing patients with skeletal Class III malocclusion using a finite element method. METHODS: An finite element model was constructed from the spiral computed tomographic images of a skull from an 11-year-old growing patient with skeletal Class III malocclusion along with BAMP, rapid maxillary expander, and the posterior bite plane. The created model had 105,189 nodes and 481,066 elements. After assigning the appropriate material properties and the boundary condition, 800 g of transverse force per side and a Class III intraoral elastic 250 g of force per side were applied to the model, and after the postprocessing, the results were obtained in the form of color bands. RESULTS: The maxilla and the attached structures were displaced and expanded transversely. The maxilla was displaced anteriorly by 0.692 mm, and the mandible was displaced backward by 0.204 mm in the sagittal direction. The anterior region of the maxilla and mandible, dentition, and nasal bone were rotated counterclockwise. Displacement in an upward direction was greatest at the symphysis region of the mandible. The stresses experienced by most of the bones were tensile, with the maxilla and maxillary dentition experiencing the maximum. CONCLUSIONS: Favorable changes were appreciated with maxillary forward and mandibular backward displacement, with appreciable tensile stresses in all the bones.
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Maloclusión de Angle Clase III , Maxilar , Humanos , Niño , Maxilar/diagnóstico por imagen , Análisis de Elementos Finitos , Técnica de Expansión Palatina , Cráneo , Maloclusión de Angle Clase III/diagnóstico por imagen , Maloclusión de Angle Clase III/terapia , Cefalometría/métodosRESUMEN
Purpose: Failure of rapid re-epithelialization within 10-14 days after corneal injury, even with standard supportive treatment, is referred to as persistent corneal epithelial (CE) defect (PED). Though an array of genes regulates reepithelization, their mechanisms are poorly understood. We sought to understand the network of genes driving the re-epithelialization in PED. Method: After obtaining informed consent, patients underwent an ophthalmic examination. Epithelial scrapes and tears samples of six PED patients and six individuals (control) undergoing photorefractive keratectomy (PRK) were collected. RNA isolation and quantification were performed using either the epithelial scrape taken from PED patients or from HCLE cells treated with control tears or tears of PED patients. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to detect the expression of a few important genes in CE homeostasis, inflammation, and cell-cell communication, viz., Kruppel-like factor 4 (KLF4), GPX4, IL6, TNFα, STING, IL8, desmoglein, and E-cadherin, among others. Their expressions were normalized with their respective housekeeping genes and fold changes were recorded. KLF4 localization and MMPs activity was carried out via immunofluorescence and zymography, respectively. Results: KLF4, a transcription factor important for CE homeostasis, was upregulated in tears-treated HCLE cells and downregulated in PED patients compared to the healthy PRK group. Cell-cell communication genes were also upregulated in tears-treated cells, whereas they were downregulated in the PED tissue group. Genes involved in proinflammation (IL6, 282-fold; TNFα, 43-fold; IL8, 4.2-fold) were highly upregulated in both conditions. MMP9 activity increased upon tears treatment. Conclusions: This study suggests that tears create an acute proinflammatory milieu driving the PED disease pathology, whereas the PED patients scrapes are an indicator of the chronic stage of the disease. Interferons, pro-inflammatory genes, and their pathways are involved in PED, which can be a potential target for inducing epithelialization of the cornea.
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Optical coherence tomography (OCT) is analogous to ultrasound biometry in the cross sectional imaging of ocular tissues. Development of current devices with deeper penetration and higher resolution has made it popular tool in clinics for visualization of anterior segment structures. In this review, the authors discussed the application of AS-OCT for diagnosis and management of various corneal and ocular surface disorders. Further, recent developments in the application of the device for pediatric corneal disorders and extending the application of OCT angiography for anterior segment are introduced.
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On 7 February 2021, Chamoli district (Uttarakhand, India) was devastated by a deadly rock-ice avalanche that led to a large causality of more than 200 people and a huge economic loss. We found noteworthy sequence of precursory signals of main failure/detachment preceded by a dynamic nucleation phase. The rock-ice avalanche appears to have been initiated by seismic precursors which were continuously active for 2:30 h prior to main detachment. The seismic amplitude, frequency characteristics and signal-to-noise ratio variation of detected tremors indicate static to dynamic changes in nucleation phase located at the source of detached wedge. The characteristics of seismic data distinguished debris flow and hitting obstacles from other seismic sources and allowed the estimations of debris flow speed. We analyzed and verified the seismic signals with field evidences to estimate the associated impacts and velocity of dynamic flow. The proximal high-quality seismic data allowed us to reconstruct the complete chronological sequence and evaluate impacts since the initiation of nucleation phase to its advancement. Furthermore, we suggest that real-time seismic monitoring with existing network and future deployment of integrated dense network can be used for forecasting of flow events and hazard mitigation in the downstream.
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Desastres , Hielo , Humanos , IndiaRESUMEN
PURPOSE: Previously we demonstrated that the secreted Ly-6/uPAR related protein-1 (SLURP1), abundantly expressed in the corneal epithelium (CE) and secreted into the tear fluid, serves as an anti-inflammatory and anti-angiogenic molecule. Here we describe the Slurp1-null (Slurp1X-/-) mouse corneal phenotype for the first time. METHODS: We compared the 10-week-old wild type (WT) and Slurp1X-/- mouse corneal (i) histology by hematoxylin-eosin and periodic acid-Schiff's reagent staining, (ii) cell proliferation by immunostaining for Ki67, (iii) cell adhesion molecules by immunostaining for desmosomal and tight junction proteins, (iv) barrier function by fluorescein staining and (v) wound-healing by epithelial debridement. Effect of SLURP1 on cell cycle was quantified in human corneal limbal epithelial (HCLE) cells engineered to express SLURP1 (HCLE-SLURP1). RESULTS: WT and Slurp1X-/- corneal histology was largely comparable, other than a few loosely attached superficial cells in Slurp1X-/- corneas. Compared with the WT, Slurp1X-/- corneas displayed (i) increase in Ki67+ cells, (ii) altered expression and/or localization of tight junction proteins Tjp1 and Pard3, and desmosomal Dsp, (iii) increased superficial fragility and (iv) slower CE wound healing. HCLE-SLURP1 cells displayed (i) decrease in Ki67+ cells, (ii) increased cell number doubling time, (iii) stalling in G1-S phase transition during cell cycle, and (iv) downregulation of cyclins CCNE and CCND1/D2, cyclin-dependent kinases CDK4 and CDK6, and upregulation of CDK inhibitor p15/CDKN2B. CONCLUSIONS: Collectively, these results elucidate that Slurp1X-/- CE cell homeostasis is altered and suggest that SLURP1 is a pro-differentiation factor that stalls G1-S transition during cell cycle progression by downregulating cyclins and upregulating p15/CDKN2B.
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Córnea , Epitelio Corneal , Animales , Córnea/metabolismo , Células Epiteliales , Epitelio Corneal/metabolismo , Antígeno Ki-67/metabolismo , Ratones , Proteínas de Uniones Estrechas/metabolismoRESUMEN
Epigenetic mechanisms modulate gene expression and function without altering the base sequence of DNA. These reversible, heritable, and environment-influenced mechanisms generate various cell types during development and orchestrate the cellular responses to external stimuli by regulating the expression of genome. Also, the epigenetic modifications influence common pathological and physiological responses including inflammation, ischemia, neoplasia, aging and neurodegeneration etc. In recent past, the field of epigenetics has gained momentum and become an increasingly important area of biomedical research As far as eye is concerned, epigenetic mechanisms may play an important role in many complex diseases such as corneal dystrophy, cataract, glaucoma, diabetic retinopathy, ocular neoplasia, uveitis, and age-related macular degeneration. Focusing on the epigenetic mechanisms in ocular diseases may provide new understanding and insights into the pathogenesis of complex eye diseases and thus can aid in the development of novel treatments for these diseases. In the present review, we summarize the clinical perspective of infectious keratitis, role of epigenetics in infectious keratitis, therapeutic potential of epigenetic modifiers and the future perspective.
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Epigénesis Genética , Infecciones del Ojo/genética , Queratitis/genética , Animales , Infecciones del Ojo/terapia , Humanos , Queratitis/terapiaRESUMEN
Exosomes are a subset of extracellular vesicles (EVs) that are secreted by most cell types. They are nanosized EVs ranging from 30 to 150 nm. The membrane-enclosed bodies originate by the process of endocytosis and mainly comprise DNA, RNA, protein, and lipids. Exosomes not only act as cell-to-cell communication signaling mediators but also have the potential to act as biomarkers for clinical application and as a promising carrier for drug delivery. Unfortunately, the purification methods for exosomes remain an obstacle. While most of the exosome researches are mainly focused on cancer, there are limited studies highlighting the importance of exosomes in ocular biology, specifically cornea-associated pathologies. Here, we summarize a brief description of exosome biogenesis, roles of exosomes and exosome-based therapies in corneal pathologies, and exosome bioengineering for tissue-specific therapy.