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1.
Transl Vis Sci Technol ; 13(8): 4, 2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-39093295

RESUMEN

Purpose: This study aims to investigate the impact of axial elongation on ganglion cell complex thickness (GCCT) and retinal capillary density (CD) using wide-field swept-source optical coherence tomography angiography. Methods: A retrospective cross-sectional analysis was conducted involving 506 eyes. Fovea-centered scans were obtained to assess the subregional GCCT and capillary density across the whole retina, the superficial capillary plexus (SCP), and deep capillary plexus (DCP) among three groups: normal control, high myopia (HM) eyes with axial length < 28 mm, and HM eyes with axial length > 28 mm. Regional variations (central vs. peripheral, quadrants difference [superior, inferior, nasal, and temporal]) were analyzed. Results: In HM eyes with axial length > 28 mm, GCCT and retinal CD exhibit a general decline in most regions (P < 0.05). In HM eyes with axial length < 28 mm, significant reductions were observed specifically in peripheral regions, as in the GCCT beyond the 3 × 3 mm2 area and CD in the 9-12 mm whole retina, 9-12 mm superior SCP, and 6-12 mm DCP (P < 0.05). Maximum GCCT and retinal CD reduction with axial elongation was observed in subregions beyond 6 × 6  mm2. Conclusions: GCCT beyond the 3 × 3 mm2 area and peripheral retinal CD beyond the 6 × 6  mm2 area were more susceptible to axial elongation and are thereby deserving of particular attention. Translational Relevance: It is necessary to evaluate different regions during the clinical assessment of the effect of myopia on the fundus and pay close attention to the peripheral retina.


Asunto(s)
Células Ganglionares de la Retina , Vasos Retinianos , Tomografía de Coherencia Óptica , Humanos , Tomografía de Coherencia Óptica/métodos , Estudios Transversales , Estudios Retrospectivos , Masculino , Células Ganglionares de la Retina/patología , Femenino , Vasos Retinianos/diagnóstico por imagen , Vasos Retinianos/patología , Persona de Mediana Edad , Adulto , Miopía/patología , Miopía/diagnóstico por imagen , Miopía/fisiopatología , Microvasos/patología , Microvasos/diagnóstico por imagen , Longitud Axial del Ojo/patología , Longitud Axial del Ojo/diagnóstico por imagen , Fibras Nerviosas/patología , Angiografía con Fluoresceína/métodos , Adulto Joven , Anciano , Capilares/patología , Capilares/diagnóstico por imagen
2.
Biosens Bioelectron ; 263: 116574, 2024 Jul 14.
Artículo en Inglés | MEDLINE | ID: mdl-39029276

RESUMEN

In this work, a platinum-nickel based nanozyme is prepared and used as a coreaction accelerator in the luminol-H2O2 electrochemiluminescence (ECL) system to construct an ECL biosensor for dimethyl phthalate (DMP) detection. The PtNi/NC nanozyme possesses dispersed metal active sites, and the synergistic effect of Pt and Ni endows it with excellent catalytic performance, which effectively converts H2O2 into more superoxide anions, and then significantly enhances the ECL intensity of the luminol system. The ECL mechanism is investigated by combining cyclic voltammetry and ECL with different types of free radical scavengers. Simultaneously, an "off-on" biosensor is constructed by integrating 3D DNA walker with enzyme-free recycling amplification for ultrasensitive detection of DMP. The biosensor based on PtNi/NC nanozyme mediated luminol-H2O2 system and 3D DNA walker exhibits a linear range of 1 × 10-16 to 1 × 10-6 M with a detection limit of 4.3 × 10-17 M (S/N = 3), and displays good stability and specificity. This study demonstrates the advantages of PtNi/NC nanozyme in enhancing the luminol-H2O2 ECL system, providing new strategy for designing efficient ECL emitter and offering a new method for detecting phthalate esters.

3.
Cont Lens Anterior Eye ; : 102169, 2024 Jul 17.
Artículo en Inglés | MEDLINE | ID: mdl-39025755

RESUMEN

PURPOSE: Vitamin D (VD) is a vitamin with anti-inflammatory and immunomodulatory effects. Several studies have shown that VD deficiency is associated with the incidence and severity of dry eye disease (DED) in humans. This meta-analysis compared signs and symptoms in patients with DED before and after VD supplementation. METHODS: Ten databases (PubMed, Cochrane, Web of science, Ovid, Embase, Scopus, CNKI, CSTJ, Wanfang, Sinomed) and four clinical trials registry websites (ISRCTN, CT, ICTRP, ICH GCP) were searched for studies on the efficacy of VD supplement in patients with DED that were published up to 2023 January. A total of 8 studies with 439 cases were included. Two reviewers independently assessed the quality of the literature and extracted data to calculate standard mean differences (SMD) for the Schirmer's test (SH test), tear film break-up time (TBUT), corneal fluorescein staining scores (CFSS, Oxford Scale, 0-5), lid hyperemia, ocular surface disease index (OSDI), and visual analogue pain scale (VAS). RESULTS: The analysis showed that VD supplementation improved tear production (SMD 1.43, 95% CI 0.81, 2.05, p = 0.000) and tear film stability (SMD 1.19, 95% CI 0.83, 1.55, p = 0.000) and reduced lid hyperemia (SMD -0.71, 95% CI -1.09, -0.32, p = 0.000) and OSDI (SMD -1.10, 95% CI -1.45, -0.74, p = 0.000), which is effective in alleviating the signs and symptoms of DED. CONCLUSIONS: VD supplementation could be an adjuvant treatment to alleviate the signs and symptoms of dry eye in the future. However, further studies regarding its most appropriate administration and dosage need to be conducted.

4.
Asia Pac J Ophthalmol (Phila) ; : 100085, 2024 Jul 24.
Artículo en Inglés | MEDLINE | ID: mdl-39059558

RESUMEN

Large language models (LLMs), a natural language processing technology based on deep learning, are currently in the spotlight. These models closely mimic natural language comprehension and generation. Their evolution has undergone several waves of innovation similar to convolutional neural networks. The transformer architecture advancement in generative artificial intelligence marks a monumental leap beyond early-stage pattern recognition via supervised learning. With the expansion of parameters and training data (terabytes), LLMs unveil remarkable human interactivity, encompassing capabilities such as memory retention and comprehension. These advances make LLMs particularly well-suited for roles in healthcare communication between medical practitioners and patients. In this comprehensive review we discuss the trajectory of LLMs and potential implications for clinicians and patients. For clinicians, LLMs can be used for automated medical documentation, and given better inputs and extensive validation, LLMs may be able to autonomously diagnose and treat in the future. For patient care, LLMs can be used for triage suggestions, summarization of medical documents, explanation of a patient's condition, and customizing patient education materials tailored to their comprehension level. The limitations of LLM and possible solutions for real world use are also presented. Given the rapid advancements in this area, this review attempts to briefly cover many roles that LLMs may play in the ophthalmic space, with a focus on improving the quality of healthcare delivery.

5.
Exp Eye Res ; 246: 110010, 2024 Jul 26.
Artículo en Inglés | MEDLINE | ID: mdl-39069000

RESUMEN

This study aimed to develop and evaluate a guinea pig model for glaucoma, comparing resultant eyeball enlargement with an existing myopia model. Thirty guinea pigs underwent intracameral injection of magnetic microspheres to induce chronic ocular hypertension (COH). Intraocular pressure (IOP) was systematically monitored, revealing a successful induction of COH in 73.33% of the guinea pigs. The mean IOP increased from a baseline of 18.04 ± 1.33 mmHg, reaching a peak at week 3 (36.31 ± 6.13 mmHg) and remaining elevated for at least 7 weeks. All data are presented as mean ± standard deviation of the mean. Subsequently, detailed assessments were conducted to validate the established glaucoma model. Immunofluorescent staining demonstrated a significant decrease in the density of retinal ganglion cells (RGC) in the glaucoma group. Optic disc excavation and notable thinning of the lamina cribrosa (LC) were observed. The quantity of optic nerve ax·ons in glaucoma group gradually decreased from baseline (44553 ± 3608/mm2) to week 4 (28687 ± 2071/mm2) and week 8 (17977 ± 3697/mm2). Moreover, regarding the global enlargement of eyeballs, both the transverse and longitudinal axis in glaucomatous eyes were found to be significantly larger than that in myopic eyes, particularly in the anterior chamber depth (1.758 ± 0.113 mm vs. 1.151 ± 0.046 mm). These findings indicate distinct patterns of structural changes associated with glaucoma and myopia in the guinea pig model. This guinea pig model holds promise for future research aimed at exploring biomechanical mechanisms, therapeutic interventions, and advancing our understanding of the relationship between glaucoma and myopia.

6.
Int Immunopharmacol ; 137: 112428, 2024 Aug 20.
Artículo en Inglés | MEDLINE | ID: mdl-38908077

RESUMEN

Herpes simplex keratitis (HSK) is a blinding disease caused by herpes simplex virus type 1 (HSV-1) infection, and rapid eradication of the virus from the affected cornea is imperative. Nod-like receptors (NLRs) are intracellular innate immune sensors closely associated with cell death, inflammation and immune responses. In this study, we investigated the role of NLRP12 in the antiviral immunology in HSK and the underlying mechanisms. We found that NLRP12 expression was significantly decreased in HSV-1-infected human corneal epithelial cells (HCE-Ts) and HSK mouse corneas. Overexpression of NLRP12 significantly reduced viral replication in infected HCE-Ts and functioned through inflammasome-mediated pyroptosis and downstream IL-18-IFN-γ axis. In HSK mouse models, overexpression of NLRP12 reduced viral replication in the cornea and alleviated HSK symptoms. This resulted from enhanced antiviral immune responses including the activation of specific immune cells in both the cornea and the draining lymph nodes. Specifically, the NLRP12-IL-18-IFN-γ axis regulated the interaction between infected corneal epithelial cells and macrophages. In conclusion, our study identified a role of NLRP12 in mediating pyroptosis and regulating antiviral immune responses. This novel finding opens the possibilities of NLRP12 as a viable target in the therapeutic strategies for HSV-1 infection.


Asunto(s)
Herpesvirus Humano 1 , Interferón gamma , Interleucina-18 , Queratitis Herpética , Ratones Endogámicos C57BL , Piroptosis , Transducción de Señal , Animales , Queratitis Herpética/inmunología , Queratitis Herpética/virología , Humanos , Interleucina-18/metabolismo , Interleucina-18/inmunología , Interferón gamma/metabolismo , Interferón gamma/inmunología , Herpesvirus Humano 1/inmunología , Herpesvirus Humano 1/fisiología , Ratones , Córnea/virología , Córnea/inmunología , Córnea/patología , Femenino , Replicación Viral , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Péptidos y Proteínas de Señalización Intracelular/genética , Modelos Animales de Enfermedad , Inflamasomas/metabolismo , Inflamasomas/inmunología , Inmunidad Innata
7.
Cell Rep Med ; 5(5): 101524, 2024 May 21.
Artículo en Inglés | MEDLINE | ID: mdl-38670096

RESUMEN

The carbonic anhydrase 2 (Car2) gene encodes the primary isoenzyme responsible for aqueous humor (AH) production and plays a major role in the regulation of intraocular pressure (IOP). The CRISPR-Cas9 system, based on the ShH10 adenovirus-associated virus, can efficiently disrupt the Car2 gene in the ciliary body. With a single intravitreal injection, Car2 knockout can significantly and sustainably reduce IOP in both normal mice and glaucoma models by inhibiting AH production. Furthermore, it effectively delays and even halts glaucomatous damage induced by prolonged high IOP in a chronic ocular hypertension model, surpassing the efficacy of clinically available carbonic anhydrase inhibitors such as brinzolamide. The clinical application of CRISPR-Cas9 based disruption of Car2 is an attractive therapeutic strategy that could bring additional benefits to patients with glaucoma.


Asunto(s)
Sistemas CRISPR-Cas , Anhidrasa Carbónica II , Cuerpo Ciliar , Glaucoma , Presión Intraocular , Animales , Glaucoma/genética , Glaucoma/patología , Glaucoma/metabolismo , Sistemas CRISPR-Cas/genética , Cuerpo Ciliar/metabolismo , Cuerpo Ciliar/patología , Anhidrasa Carbónica II/genética , Anhidrasa Carbónica II/metabolismo , Ratones , Humor Acuoso/metabolismo , Humanos , Modelos Animales de Enfermedad , Inhibidores de Anhidrasa Carbónica/farmacología , Inhibidores de Anhidrasa Carbónica/uso terapéutico , Eliminación de Gen , Ratones Endogámicos C57BL , Hipertensión Ocular/genética , Hipertensión Ocular/patología
8.
J Pharmacol Exp Ther ; 390(1): 45-52, 2024 Jun 21.
Artículo en Inglés | MEDLINE | ID: mdl-38272670

RESUMEN

Therapeutic vaccines containing aluminum adjuvants have been widely used in the treatment of tumors due to their powerful immune-enhancing effects. However, the neurotoxicity of aluminum adjuvants with different physicochemical properties has not been completely elucidated. In this study, a library of engineered aluminum oxyhydroxide (EAO) and aluminum hydroxyphosphate (EAHP) nanoparticles was synthesized to determine their neurotoxicity in vitro. It was demonstrated that the surface charge of EAHPs and size of EAOs did not affect the cytotoxicity in N9, bEnd.3, and HT22 cells; however, soluble aluminum ions trigger the cytotoxicity in three different cell lines. Moreover, soluble aluminum ions induce apoptosis in N9 cells, and further mechanistic studies demonstrated that this apoptosis was mediated by mitochondrial reactive oxygen species generation and mitochondrial membrane potential loss. This study identifies the safety profile of aluminum-containing salts adjuvants in the nervous system during therapeutic vaccine use, and provides novel design strategies for their safer applications. SIGNIFICANCE STATEMENT: In this study, it was demonstrated that engineered aluminum oxyhydroxide and aluminum hydroxyphosphate nanoparticles did not induce cytotoxicity in N9, bEnd.3, and HT22 cells. In comparation, soluble aluminum ions triggered significant cytotoxicity in three different cell lines, indicating that the form in which aluminum is presenting may play a crucial role in its safety. Moreover, apoptosis induced by soluble aluminum ions was dependent on mitochondrial damage. This study confirms the safety of engineered aluminum adjuvants in vaccine formulations.


Asunto(s)
Adyuvantes Inmunológicos , Apoptosis , Vacunas contra el Cáncer , Nanopartículas , Adyuvantes Inmunológicos/farmacología , Animales , Nanopartículas/química , Apoptosis/efectos de los fármacos , Ratones , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Humanos , Línea Celular , Aluminio/química , Aluminio/toxicidad , Compuestos de Aluminio/toxicidad
9.
J Control Release ; 365: 208-218, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37981051

RESUMEN

Herpes simplex keratitis (HSK) is a common blinding corneal disease caused by herpes simplex virus type 1 (HSV-1) infection. Antiviral drugs and corticosteroids haven't shown adequate therapeutic efficacy. During the early stage of HSV-1 infection, macrophages serve as the first line of defense. In particular, CD169+ macrophages play an important role in phagocytosis and antigen presentation. Therefore, we constructed GM-gD-lip, a ganglioside GM1 liposome vaccine encapsulating HSV-1 glycoprotein D and targeting CD169+ macrophages. After subconjunctival injection of the vaccine, we evaluated the survival rate and ocular surface lesions of the HSK mice, as well as the virus levels in the tear fluid, corneas, and trigeminal ganglia. We discovered that GM-gD-lip reduced HSV-1 viral load and alleviated the clinical severity of HSK. The GM-gD-lip also increased the number of corneal infiltrating macrophages, especially CD169+ macrophages, and polarized them toward M1. Furthermore, the number of dendritic cells (DCs) and CD8+ T cells in the ocular draining lymph nodes was significantly increased. These findings demonstrated that GM-gD-lip polarized CD169+ macrophages toward M1 to eliminate the virus while cross-presenting antigens to CD8+ T cells via DCs to activate adaptive immunity, ultimately attenuating the severity of HSK. The use of GM-gD-lip as an immunotherapeutic method for the treatment of HSK has significant implications.


Asunto(s)
Herpes Simple , Herpesvirus Humano 1 , Queratitis Herpética , Vacunas , Animales , Ratones , Liposomas , Linfocitos T CD8-positivos , Gangliósidos , Queratitis Herpética/tratamiento farmacológico , Herpesvirus Humano 1/fisiología , Córnea , Macrófagos , Glicoproteínas
10.
Acta Ophthalmol ; 102(2): e168-e177, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38129974

RESUMEN

PURPOSE: To compare the diagnostic performance of the capillary density (CD) of the central 1-6 mm and peripheral 6-12 mm annular regions in detecting open-angle glaucoma in high myopia (HM) using 15 × 12 mm wide-field swept-source optical coherence tomography angiography (WF SS-OCTA). METHODS: The study enrolled 206 and 103 eyes with HM and highly myopic open-angle glaucoma (HM-OAG), respectively. WF SS-OCTA images centred on the fovea were obtained to analyse the changes in the CD in the 1-3 mm, 3-6 mm, 6-9 mm, and 9-12 mm annular regions. CD of the superficial capillary plexus (SCP) was measured with the built-in software. The area under the receiver operating characteristic curve (AUROC) of each region was compared. RESULTS: The diagnostic performance of the SCP CD in the central 1-6 mm annular region (AUROC = 0.849) was better than that in the peripheral 6-12 mm annular region (AUROC = 0.756, p = 0.001). The annular AUROCs of SCP CD peaked in the 3-6 mm annular region (AUROC = 0.858) and gradually decreased with increasing diameter and were lower than the corresponding AUROCs of the ganglion cell-inner plexiform layer thickness (p < 0.05 for all comparisons). SCP CD of the inferior quadrant in the 3-6 mm annular region had the best diagnostic performance (AUROC = 0.859). CONCLUSION: The SCP CD in the central 1-6 mm annular region exhibited better diagnostic performance for the detection of HM-OAG in HM. The assessment of more peripheral regions has no added value in detecting glaucoma in HM.


Asunto(s)
Glaucoma de Ángulo Abierto , Miopía , Humanos , Glaucoma de Ángulo Abierto/diagnóstico , Tomografía de Coherencia Óptica/métodos , Células Ganglionares de la Retina , Presión Intraocular , Campos Visuales , Miopía/diagnóstico , Angiografía , Vasos Retinianos
11.
Heliyon ; 9(9): e19971, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37809549

RESUMEN

Purpose: To evaluate the effects of chalazion excision on the ocular surface, taking into account the subjective symptoms and the objective parameters of the tear film. Methods: This prospective, interventional clinical study included 52 eyes from 26 patients with eyelid chalazion who underwent excision of the lesions between March and August 2022. Chalazion excision was performed on the patient's chalazion eye, and the contralateral eye served as the control. The following parameters were investigated both preoperatively and 1 week, 1 month, and 3 months postoperatively: the Ocular Surface Disease Index (OSDI), Schirmer I test, corneal fluorescein stain (CFS), tear meniscus height (TMH), noninvasive first breakup time (NifBUT), noninvasive average breakup time (NiaBUT), bulbar conjunctival redness score, the thickness of the lipid layer, and meibomian gland loss. Results: Before surgery, the OSDI score of the chalazion eye was significantly higher than the contralateral eye. The bulbar conjunctival redness score (p = 0.043) and the OSDI score (p = 0.004) improved significantly in the first month after surgery. In the third month after surgery, the objective parameters showed significant improvements, including TMH (p = 0.032), NiaBUT (p = 0.028), bulbar conjunctival redness score (p < 0.001), the thickness of the lipid layer (p = 0.021), and meibomian gland loss (p = 0.005). Conclusions: Our study revealed that chalazion excision can significantly improve the subjective symptoms and the objective tear film parameters of the ocular surface.

12.
Sci Data ; 10(1): 653, 2023 09 23.
Artículo en Inglés | MEDLINE | ID: mdl-37741836

RESUMEN

Mice have emerged as a widely employed model for investigating various retinal diseases. However, the availability of comprehensive datasets capturing the entire developmental and aging stages of the mouse retina, particularly during the elderly period, encompassing integrated lncRNA and mRNA expression profiles, is limited. In this study, we assembled a total of 18 retina samples from mice across 6 distinct stages of development and aging (5 days, 3 weeks, 6 weeks, 10 weeks, 6 months, and 15 months) to conduct integrated lncRNA and mRNA sequencing analysis. This invaluable dataset offers a comprehensive transcriptomic resource of mRNA and lncRNA expression profiles during the natural progression of retinal development and aging. The discoveries stemming from this investigation will significantly contribute to the elucidation of the underlying molecular mechanisms associated with various retinal diseases, such as congenital retinal dysplasia and retinal degenerative diseases.


Asunto(s)
ARN Largo no Codificante , Retina , Animales , Ratones , Envejecimiento/genética , Perfilación de la Expresión Génica , Retina/crecimiento & desarrollo , Degeneración Retiniana/genética , ARN Largo no Codificante/genética , ARN Mensajero/genética , Displasia Retiniana/genética , Humanos
13.
Pharmaceuticals (Basel) ; 16(9)2023 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-37765049

RESUMEN

Herpes simplex keratitis (HSK) is a blinding eye disease that is initiated by the herpes simplex virus type 1 (HSV-1). Resistance to acyclovir (ACV) and the side effects of corticosteroid drugs have become concerning issues, so it is crucial to develop new antivirals for treating HSK. In this study, we report that biochanin A (BCA), a naturally occurring flavonoid compound, provides multifaceted protective effects with anti-viral, anti-inflammatory, anti-oxidative stress and anti-apoptotic activities to alleviate HSK. The results show that BCA significantly inhibited HSV-1 replication in vitro and further proved that BCA principally influenced the early stage of virus infection. We reveal that BCA downregulated the expression of pro-inflammatory factors triggered by HSV-1, including TNF-α, RANTES, IL-1ß and IL-6. Furthermore, BCA treatment alleviated oxidative stress and apoptotic arising from HSV-1 infection. Lastly, we induced HSK in male C57BL/6 mice and treated them with either BCA or phosphate buffer solution (PBS) eye drops. We observed the ocular surface lesions; determined the virus load in the tear fluid, corneas as well as trigeminal ganglions (TGs); and detected the levels of inflammation and apoptosis in the corneas simultaneously. These results show that BCA inhibits HSV-1 and alleviates the corneal lesion degree. Our study illustrates that BCA is a promising therapeutic approach for application in treating HSK.

14.
Diabetes Metab Res Rev ; 39(7): e3673, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37302139

RESUMEN

We aimed to summarise current evidence on different antidiabetic drugs to delay cognitive impairment, including mild cognitive impairment, dementia, Alzheimer's disease (AD) and vascular dementia, among subjects with type 2 diabetes mellitus (T2DM). Medline, Cochrane and Embase databases were searched from inception to 31 July 2022. Two investigators independently reviewed and screened trials comparing antidiabetic drugs with no antidiabetic drugs, placebo, or other active antidiabetic drugs on cognitive outcomes in T2DM. Data were analysed using meta-analysis and network meta-analysis. Twenty-seven studies met the inclusion criteria, including 3 randomised controlled trials, 19 cohort studies and 5 case-control studies. Compared with non-user, SGLT-2i (OR 0.41 [95% CI 0.22-0.76]), GLP-1RA (OR 0.34 [95% CI 0.14-0.85]), thiazolidinedione (OR 0.60 [95% CI 0.51-0.69]), and DPP-4i (OR 0.78 [95% CI 0.61-0.99]) users had a decreased risk of dementia, whereas sulfonylurea (OR 1.43 [95% CI 1.11-1.82]) increased dementia risk. Network meta-analysis showed that SGLT-2i was most likely to rank best (SUCRA = 94.4%), GLP-1 RA second best (SUCRA = 92.7%), thiazolidinedione third best (SUCRA = 74.7%) and DPP-4i fourth best (SUCRA = 54.9%), while sulfonylurea second worst (SUCRA = 20.0%) for decreasing dementia outcomes, by synthesising evidence from direct and indirect comparisons of multiple intervention. Evidence suggests the effects of SGLT-2i ≈ GLP-1 RAs > thiazolidinedione > DPP-4i for delaying cognitive impairment, dementia and AD outcomes, whereas sulfonylurea was associated with the highest risk. These findings provide evidence for evaluating the optional treatment for clinical practice. PROSPERO REGISTRATION: Registration no. CRD42022347280.


Asunto(s)
Demencia , Diabetes Mellitus Tipo 2 , Inhibidores de la Dipeptidil-Peptidasa IV , Tiazolidinedionas , Humanos , Hipoglucemiantes/uso terapéutico , Hipoglucemiantes/farmacología , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/complicaciones , Metaanálisis en Red , Compuestos de Sulfonilurea/uso terapéutico , Péptido 1 Similar al Glucagón/uso terapéutico , Demencia/epidemiología , Demencia/complicaciones , Tiazolidinedionas/uso terapéutico , Cognición , Inhibidores de la Dipeptidil-Peptidasa IV/uso terapéutico , Inhibidores de la Dipeptidil-Peptidasa IV/farmacología , Receptor del Péptido 1 Similar al Glucagón
15.
Int Immunopharmacol ; 121: 110397, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37302369

RESUMEN

Dry eye disease (DED) is a multifactorial disease, and oxidative stress plays a crucial role in its pathogenesis. Recently, multiple studies have shown that upregulation of autophagy can protect the cornea from oxidative stress damage. The present study investigated the therapeutic effects of salidroside, the main component of Rhodiola crenulata, in both in vivo and in vitro dry eye models. The results showed that topical eye drop treatment with salidroside restored corneal epithelium damage, increased tear secretion, and reduced cornea inflammation in the DED mice. Salidroside activated autophagy through AMP-activated protein kinase (AMPK)-sirtuin-1 (Sirt1) signaling pathway, which promoted the nuclear translocation of nuclear factor erythroid-2-related factor 2 (Nrf2) and increased the expression of downstream antioxidant factors heme oxygenase-1 (HO-1) and NAD(P)H quinone dehydrogenase 1 (NQO1). This process restored antioxidant enzyme activity, reduced reactive oxygen species (ROS) accumulation, and alleviated oxidative stress. The application of autophagy inhibitor chloroquine and AMPK inhibitor Compound C reversed the therapeutic efficacy of salidroside, validating the above findings. In conclusion, our data suggest that salidroside is a promising candidate for DED treatment.


Asunto(s)
Proteínas Quinasas Activadas por AMP , Antioxidantes , Animales , Ratones , Antioxidantes/farmacología , Proteínas Quinasas Activadas por AMP/metabolismo , Sirtuina 1/metabolismo , Estrés Oxidativo , Especies Reactivas de Oxígeno/metabolismo , Autofagia , Factor 2 Relacionado con NF-E2/metabolismo
16.
Front Med (Lausanne) ; 10: 1149803, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36993811

RESUMEN

Purpose: To evaluate the subclinical changes in corneal dendritic cell density (CDCD) and corneal subbasal nerve density (CSND) in asymptomatic contact lens (CL) wearers. Methods: Databases including PubMed, Scopus, Web of Science, and Cochrane Central Register of Controlled Trials were searched for trials and studies reporting the changes of corneal CDCD and CSND in contact lens wearers published until 25 June 2022. PRISMA guidelines as well as recommended meta-analysis practices were followed. Meta-analysis was conducted using RevMan V.5.3 software. Results: After the screening, 10 studies with 587 eyes of 459 participants were included. Seven studies reported the data of CDCD. Compared with the control group, CDCD in the CL wearers was higher (18.19, 95% CI 18.8-27.57, p = 0.0001). Type of in vivo confocal microscopy (IVCM), wear duration, and frequency of lens change were sources of heterogeneity. The difference in CSND between CL wearers and the control group was insignificant, and subgroup analysis did not reveal a source of heterogeneity. Conclusion: Overall, CDCD increased in CL wears, while CSND did not show significant differences. IVCM is a feasible tool to assess subclinical changes in CL wearers.

17.
Front Genet ; 14: 1088455, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36891151

RESUMEN

TP53 (or p53) is widely accepted to be a tumor suppressor. Upon various cellular stresses, p53 mediates cell cycle arrest and apoptosis to maintain genomic stability. p53 is also discovered to suppress tumor growth through regulating metabolism and ferroptosis. However, p53 is always lost or mutated in human and the loss or mutation of p53 is related to a high risk of tumors. Although the link between p53 and cancer has been well established, how the different p53 status of tumor cells help themselves evade immune response remains largely elusive. Understanding the molecular mechanisms of different status of p53 and tumor immune evasion can help optimize the currently used therapies. In this context, we discussed the how the antigen presentation and tumor antigen expression mode altered and described how the tumor cells shape a suppressive tumor immune microenvironment to facilitate its proliferation and metastasis.

18.
Analyst ; 148(6): 1362-1370, 2023 Mar 13.
Artículo en Inglés | MEDLINE | ID: mdl-36857724

RESUMEN

Exploring new highly efficient electrochemiluminescence (ECL) luminophores is a necessary condition for developing ultrasensitive ECL biosensors. Therefore, a luminescent carbon dot-based covalent organic framework (CD-COF) was prepared using aldehyde-based carbon dots (CDs) and 1,3,5-tris (4-aminophenyl) benzene (TPB). Because the CD-COF made the regular arrangement of CDs conducive to improving the ECL response, CD-COF had a higher ECL intensity and efficiency than CDs. What's more, the ECL intensity of the CD-COF/S2O82-/Bu4N+ system was about 2.98, 7.50, and 28.08 times higher than those of the CD-COF/S2O82-, CDs/S2O82- and S2O82- systems, respectively. Considering the remarkable ECL performance, the CD-COF/S2O82-/Bu4N+ system was employed combined with the CRISPR/Cas12a trans-cutting strategy to construct an "off-on" ECL biosensor for BPA detection. The proposed ECL biosensor exhibited excellent performance with a wide linear range from 1.0 × 10-14 mol L-1 to 1.0 × 10-5 mol L-1 with a low detection limit of 2.21 fM (S/N = 3) under the optimized conditions. The biosensor demonstrated that CD-COF can be used as an efficient ECL emitter, thus expanding the application field of COFs. In addition, the good stability and specificity of the biosensor enabled the rapid detection of BPA, which will provide valuable insights into promising ultrasensitive ECL biosensors.


Asunto(s)
Técnicas Biosensibles , Estructuras Metalorgánicas , Carbono , Sistemas CRISPR-Cas , Mediciones Luminiscentes , Técnicas Electroquímicas , Límite de Detección
19.
Front Pharmacol ; 13: 1048978, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36532743

RESUMEN

Herpes simplex keratitis (HSK) is a severe, infectious corneal disease caused by herpes simplex virus type 1 (HSV-1) infection. The increasing prevalence of acyclovir resistance, the side effects of hormonal drugs, and the ease of recurrence after surgery have made it crucial to develop new methods of treating HSK. HSV-1 evades the host immune response through various mechanisms. Therefore, we explored the role of the immunogenic cell death inducer PKHB1 peptide in HSK. After subconjunctival injection of PKHB1 peptide, we observed the ocular surface lesions and survival of HSK mice and detected the virus levels in tear fluid, corneas, and trigeminal ganglions. We found that PKHB1 peptide reduced HSV-1 levels in the eye and alleviated the severity of HSK. Moreover, it increased the number of corneal infiltrating antigen-presenting cells (APCs), such as macrophages and dendritic cells, and CD8+ T cells in ocular draining lymph nodes. We further observed that PKHB1 peptide promoted the exposure of calreticulin, as well as the release of ATP and high-mobility group box 1 in HSV-1-infected cells in vitro. Our findings suggested that PKHB1 peptide promoted the recruitment and maturation of APCs by inducing the release of large amounts of damage-associated molecular patterns from infected cells. APCs then phagocytized antigenic materials and translocated to the lymph nodes, triggering a cytotoxic T lymphocyte-dependent immune response that ultimately alleviated HSK.

20.
Biomed Res Int ; 2022: 6293095, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35978641

RESUMEN

With the continuous improvement of human living standards, people's demand for health has become an important international research hotspot. In recent years, 41.3% of the total incidence of multiple organ failure (MOF) caused by dysfunction of the intestinal screen was found every year. The mortality rate is 62%, which is more than twice that of developed countries. This paper is aimed at observing the microscopic effects of probiotics derived from dairy products using Caco-2 cells on intestinal barrier function. Based on the above background, the purpose of this study was to construct a Caco-2 cell model under microscope to study the effect of probiotics on intestinal barrier function. This study first describes the background knowledge of the integration of modern microscope technology and medical field and the correlation between them. The results showed that the relative adhesion rates of Lactobacillus bulgaricus, Lactobacillus acidophilus, and Streptococcus thermophilus were 4.67 ± 0.07%, 11.53 ± 0.06%, and 18.31 ± 0.08%, respectively, which were lower than those in the normal group. The production of antibacterial substances can inhibit intestinal pathogens and adjust the balance of intestinal flora.


Asunto(s)
Probióticos , Células CACO-2 , Productos Lácteos/microbiología , Humanos , Lactobacillus acidophilus , Probióticos/metabolismo , Probióticos/farmacología , Streptococcus thermophilus
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