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1.
Exp Eye Res ; 245: 109974, 2024 Jun 17.
Artículo en Inglés | MEDLINE | ID: mdl-38897271

RESUMEN

Various corneal diseases are strongly associated with corneal biomechanical characteristics, and early measurement of patients' corneal biomechanics can be utilized in their diagnosis and treatment. Measurement methods for corneal biomechanical characteristics are classified into ex vivo and in vivo. Some of these methods can directly measure certain corneal biomechanical parameters, while others require indirect calculation through alternative methods. However, due to diversities in measurement techniques and environmental conditions, significant differences may exist in the corneal mechanical properties measured by these two methods. Therefore, comprehensive research on current measurement methods and the exploration of novel measurement techniques may have great clinical significance. The corneal elastic modulus, a critical indicator in corneal biomechanics, reflects the cornea's ability to return to its initial shape after undergoing stress. This review aims to provide a comprehensive summary of the corneal elastic modulus, which is a critical biomechanical parameter, and discuss its direct, indirect, and potential measurement methods and clinical applications.

2.
Plant Genome ; : e20478, 2024 Jun 12.
Artículo en Inglés | MEDLINE | ID: mdl-38863371

RESUMEN

The small heat shock proteins (sHSPs) are important components in plant growth and development, and stress response. However, a systematical understanding of the sHSP family is yet to be reported in five diploid Gossypium species. In this study, 34 GlsHSPs, 36 GrsHSPs, 37 GtsHSPs, 37 GasHSPs, and 38 GhesHSPs were identified in Gossypium longicalyx, Gossypium raimondii, Gossypium turneri, Gossypium arboreum, and Gossypium herbaceum, respectively. These sHSP members can be clustered into 10 subfamilies. Different subfamilies had different member numbers, motif distributions, gene structures, gene duplication events, gene loss numbers, and cis-regulatory elements. Besides, the paleohexaploidization event in cotton ancestor led to expanding the sHSP members and it was also inherited by five diploid Gossypium species. After the cotton ancestor divergence, the sHSP members had the relatively conserved evolution in five diploid Gossypium species. The comprehensive evolutionary history of the sHSP family was revealed in five diploid Gossypium species. Furthermore, several GasHSPs and GhesHSPs were important candidates in plant growth and development, and stress response. These current findings can provide valuable information for the molecular evolution and further functional research of the sHSP family in cotton.

3.
Nat Commun ; 15(1): 5325, 2024 Jun 22.
Artículo en Inglés | MEDLINE | ID: mdl-38909045

RESUMEN

Garnet oxide is one of the most promising solid electrolytes for solid-state lithium metal batteries. However, the traditional interface modification layers cannot completely block electron migrating from the current collector to the interior of the solid-state electrolyte, which promotes the penetration of lithium dendrites. In this work, a highly electron-blocking interlayer composed of potassium fluoride (KF) is deposited on garnet oxide Li6.4La3Zr1.4Ta0.6O12 (LLZTO). After reacting with melted lithium metal, KF in-situ transforms to KF/LiF interlayer, which can block the electron leakage and inhibit lithium dendrite growth. The Li symmetric cells using the interlayer show a long cycle life of ~3000 hours at 0.2 mA cm-2 and over 350 hours at 0.5 mA cm-2 respectively. Moreover, an ionic liquid of LiTFSI in C4mim-TFSI is screened to wet the LLZTO|LiNi0.8Co0.1Mn0.1O2 (NCM) positive electrode interfaces. The Li|KF-LLZTO | NCM cells present a specific capacity of 109.3 mAh g-1, long lifespan of 3500 cycles and capacity retention of 72.5% at 25 °C and 2 C (380 mA g-1) with an average coulombic efficiency of 99.99%. This work provides a simple and integrated strategy on high-performance quasi-solid-state lithium metal batteries.

4.
Exp Eye Res ; 243: 109900, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38636803

RESUMEN

A pterygium is a wedge-shaped fibrovascular growth of the conjunctiva membrane that extends onto the cornea, which is the outer layer of the eye. It is also known as surfer's eye. Growth of a pterygium can also occur on the either side of the eye, attaching firmly to the sclera. Pterygia are one of the world's most common ocular diseases. However, the pathogenesis remains unsolved to date. As the pathogenesis of pterygium is closely related to finding the ideal treatment, a clear understanding of the pathogenesis will lead to better treatment and lower the recurrence rate, which is notably high and more difficult to treat than a primary pterygium. Massive studies have recently been conducted to determine the exact causes and mechanism of pterygia. We evaluated the pathogenetic factors ultraviolet radiation, viral infection, tumor suppressor genes p53, growth factors, oxidative stress, apoptosis and neuropeptides in the progression of the disease. The heightened expression of TRPV1 suggests its potential contribution in the occurrence of pterygium, promoting its inflammation and modulating sensory responses in ocular tissues. Subsequently, the developmental mechanism of pterygium, along with its correlation with dry eye disease is proposed to facilitate the identification of pathogenetic factors for pterygia, contributing to the advancement of understanding in this area and may lead to improved surgical outcomes.


Asunto(s)
Pterigion , Pterigion/etiología , Pterigion/metabolismo , Humanos , Factores de Riesgo , Estrés Oxidativo , Rayos Ultravioleta/efectos adversos , Apoptosis , Conjuntiva/patología
5.
Hum Vaccin Immunother ; 20(1): 2338953, 2024 Dec 31.
Artículo en Inglés | MEDLINE | ID: mdl-38658178

RESUMEN

This study aims to examine the development trend of COVID-19 in China and propose a model to assess the impacts of various prevention and control measures in combating the COVID-19 pandemic. Using COVID-19 cases reported by the National Health Commission of China from January 2, 2020, to January 2, 2022, we established a Susceptible-Exposed-Infected-Asymptomatic-Quarantined-Vaccinated-Hospitalized-Removed (SEIAQVHR) model to calculate the COVID-19 transmission rate and Rt effective reproduction number, and assess prevention and control measures. Additionally, we built a stochastic model to explore the development of the COVID-19 epidemic. We modeled the incidence trends in five outbreaks between 2020 and 2022. Some important features of the COVID-19 epidemic are mirrored in the estimates based on our SEIAQVHR model. Our model indicates that an infected index case entering the community has a 50%-60% chance to cause a COVID-19 outbreak. Wearing masks and getting vaccinated were the most effective measures among all the prevention and control measures. Specifically targeting asymptomatic individuals had no significant impact on the spread of COVID-19. By adjusting prevention and control parameters, we suggest that increasing the rates of effective vaccination and mask-wearing can significantly reduce COVID-19 cases in China. Our stochastic model analysis provides a useful tool for understanding the COVID-19 epidemic in China.


Asunto(s)
Vacunas contra la COVID-19 , COVID-19 , SARS-CoV-2 , Vacunación , Humanos , COVID-19/prevención & control , COVID-19/epidemiología , China/epidemiología , Vacunación/estadística & datos numéricos , SARS-CoV-2/inmunología , Vacunas contra la COVID-19/administración & dosificación , Brotes de Enfermedades/prevención & control , Incidencia , Adulto , Número Básico de Reproducción , Persona de Mediana Edad
6.
PLoS One ; 19(4): e0299376, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38630738

RESUMEN

AIM OF THE STUDY: To evaluate the therapeutic effect of SYNC in diarrhea irritable bowel syndrome (IBS-D) and explore its underlying mechanism through transcriptomic sequencing (RNA-Seq). MATERIALS AND METHODS: A rat model of IBS-D was constructed to elucidate the effects of SYNC. Abdominal withdrawal reflex (AWR), fecal water content (FWC), and recording body weight were calculated to assess visceral sensitivity in rats. Histopathological changes in the colon and alterations in mast cell (MC) count were determined. Immunohistochemistry was employed to assess mast cell tryptase (MCT) expression in rat colons. Serum levels of corticotropin-releasing Hormone (CRH), interleukin-6 (IL-6), calcitonin gene-related peptide (CGRP), and 5-hydroxytryptamine (5-HT) were quantified using ELISA. RNA-Seq of colon tissue was performed, followed by Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. Western blot analysis was conducted to quantify the expression levels of key proteins in the Nr4a3 pathway in the colon and hypothalamus tissues of rats. RESULTS: SYNC alleviated visceral hypersensitivity and mood disorders in rats with IBS-D. Moreover, it was positively correlated with its dosage and the observed effects, such as the enhancement of the colon's mucosal lining condition and reduction in the number and activation of MCs within the model group. SYNC reduced the expression levels of factors related to the brain-gut axis and inflammatory markers in the bloodstream. RNA-Seq analysis indicated that SYNC down-regulated the expression of Nr4a3 and PI3K. These SYNC-targeted genes primarily played roles in immune regulation and inflammatory responses, correlating with the modulation of Nr4a3 and the PI3K/AKT pathway. Western blot analysis further confirmed SYNC's influence on inflammation-related MC activation by downregulating key proteins in the Nr4a3/PI3K pathway. CONCLUSIONS: SYNC inhibited mast cell activation and attenuated visceral hypersensitivity in the colon tissues of IBS-D rats. These effects were mediated by the Nr4a3/PI3K signaling pathway.


Asunto(s)
Síndrome del Colon Irritable , Ratas , Animales , Síndrome del Colon Irritable/patología , Ratas Sprague-Dawley , Fosfatidilinositol 3-Quinasas , Diarrea , Hormona Liberadora de Corticotropina/metabolismo , Proteínas de Unión al ADN , Proteínas del Tejido Nervioso
7.
J Cell Mol Med ; 28(6): e18156, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38429902

RESUMEN

This study aimed to identify genes shared by metabolic dysfunction-associated fatty liver disease (MASH) and diabetic nephropathy (DN) and the effect of extracellular matrix (ECM) receptor interaction genes on them. Datasets with MASH and DN were downloaded from the Gene Expression Omnibus (GEO) database. Pearson's coefficients assessed the correlation between ECM-receptor interaction genes and cross talk genes. The coexpression network of co-expression pairs (CP) genes was integrated with its protein-protein interaction (PPI) network, and machine learning was employed to identify essential disease-representing genes. Finally, immuno-penetration analysis was performed on the MASH and DN gene datasets using the CIBERSORT algorithm to evaluate the plausibility of these genes in diseases. We found 19 key CP genes. Fos proto-oncogene (FOS), belonging to the IL-17 signalling pathway, showed greater centrality PPI network; Hyaluronan Mediated Motility Receptor (HMMR), belonging to ECM-receptor interaction genes, showed most critical in the co-expression network map of 19 CP genes; Forkhead Box C1 (FOXC1), like FOS, showed a high ability to predict disease in XGBoost analysis. Further immune infiltration showed a clear positive correlation between FOS/FOXC1 and mast cells that secrete IL-17 during inflammation. Combining the results of previous studies, we suggest a FOS/FOXC1/HMMR regulatory axis in MASH and DN may be associated with mast cells in the acting IL-17 signalling pathway. Extracellular HMMR may regulate the IL-17 pathway represented by FOS through the Mitogen-Activated Protein Kinase 1 (ERK) or PI3K-Akt-mTOR pathway. HMMR may serve as a signalling carrier between MASH and DN and could be targeted for therapeutic development.


Asunto(s)
Nefropatías Diabéticas , Interleucina-17 , Humanos , Fosfatidilinositol 3-Quinasas , Biología Computacional , Aprendizaje Automático
8.
Front Physiol ; 15: 1374627, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38529484

RESUMEN

Recent advancements in the field of endothelial markers of lymphatic vessels and lymphangiogenic factors have shed light on the association between several ocular diseases and ocular nascent lymphatic vessels. The immune privilege of corneal tissue typically limits the formation of lymphatic vessels in a healthy eye. However, vessels in the eyes can potentially undergo lymphangiogenesis and be conditionally activated. It is evident that nascent lymphatic vessels in the eyes contribute to various ocular pathologies. Conversely, lymphatic vessels are present in the corneal limbus, ciliary body, lacrimal glands, optic nerve sheaths, and extraocular muscles, while a lymphatic vasculature-like system exists in the choroid, that can potentially cause several ocular pathologies. Moreover, numerous studies indicate that many ocular diseases can influence or activate nascent lymphatic vessels, ultimately affecting patient prognosis. By understanding the mechanisms underlying the onset, development, and regression of ocular nascent lymphatic vessels, as well as exploring related research on ocular diseases, this article aims to offer novel perspectives for the treatment of such conditions.

9.
J Physiol Biochem ; 80(2): 465-477, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38526704

RESUMEN

Hypothermia is an essential environmental factor in gastrointestinal diseases, but the main molecular mechanisms of pathogenesis remain unclear. The current study sought to better understand how chronic cold stress affects gut damage and its underlying mechanisms. In this work, to establish chronic cold stress (CS)-induced intestinal injury model, mice were subjected to continuous cold exposure (4 °C) for 3 h per day for 3 weeks. Our results indicated that CS led to gut injury via inducing changes of heat shock proteins 70 (HSP70) and apoptosis-related (caspases-3, Bax and Bcl-2) proteins; enhancing expression of intestinal tight-related (ZO-1 and occludin) proteins; promoting releases of inducible nitric oxide synthase (iNOS), tumor necrosis factor-α (TNF-α), cyclooxygenase-2 (COX-2), high mobility group box 1 (HMGB1), interleukin1ß (IL-1ß), IL-18 and IL-6 inflammatory mediators in the ileum; and altering gut microbial diversity. Furthermore, persistent cold exposure resulted in the cleavage of pyroptosis-related Gasdermin D (GSDMD) protein by regulating the NLRP3/ASC/caspase-1 and caspase-11 pathway, and activation of toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88)-mediated nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways, which are strongly associated with changes in gut microbiota diversity. Taken together, these investigations provide new insights into the increased risk of intestinal disorders at extremely low temperatures and establish a theoretical foundation for the advancement of novel pharmaceutical interventions targeting cold-related ailments.


Asunto(s)
Gasderminas , Microbioma Gastrointestinal , Piroptosis , Animales , Masculino , Ratones , Ratones Endogámicos C57BL , Respuesta al Choque por Frío , Proteínas de Unión a Fosfato/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Íleon/metabolismo , Íleon/microbiología , Íleon/patología , Inflamación/metabolismo , Transducción de Señal , Receptor Toll-Like 4/metabolismo , Péptidos y Proteínas de Señalización Intracelular/metabolismo
10.
J Ocul Pharmacol Ther ; 40(3): 160-172, 2024 04.
Artículo en Inglés | MEDLINE | ID: mdl-38394222

RESUMEN

Fungal keratitis (FK) is a dangerous corneal infection that is common in tropical and subtropical areas. Its incidence is extremely high, and ocular trauma and contact lenses can lead to FK, but its common treatment such as using topical antifungal eye drop instillation is often less effective because of several drawbacks of the drugs typically used, including limited ocular penetration, high frequency of dosing, poor biocompatibility, and the potential for severe drug reactions. Therefore, the development of novel drug delivery devices for the treatment of FK is urgent. The urgent need for novel drug delivery devices to treat FK has led to the development of several techniques, including nanoparticles (NPs), in situ forming hydrogels, contact lenses, and microneedles (MNs). However, it is important to note that the main mechanisms differ between these techniques. NPs can transport large amounts of drugs and be taken up by cells owing to their large surface area and small size. In situ forming hydrogels can significantly extend the residence time of drugs because of their strong adhesive properties. Contact lenses, with their comfortable shape and drug-carrying capacity, can also act as drug delivery devices. MNs can create channels in the cornea, bypassing its barrier and enhancing drug bioavailability. This article will go over novel medication delivery techniques for treating FK and make a conclusion about their advantages and limitations in anticipation to serve the best option for the individual therapy of FK.


Asunto(s)
Úlcera de la Córnea , Infecciones Fúngicas del Ojo , Queratitis , Humanos , Úlcera de la Córnea/tratamiento farmacológico , Sistemas de Liberación de Medicamentos/métodos , Queratitis/tratamiento farmacológico , Queratitis/microbiología , Infecciones Fúngicas del Ojo/tratamiento farmacológico , Infecciones Fúngicas del Ojo/microbiología , Hidrogeles
11.
Artículo en Inglés | MEDLINE | ID: mdl-38341816

RESUMEN

The positive detection rate of blood metagenomic next-generation sequencing (mNGS) was still too low to meet clinical needs, while pus from the site of primary infection may be advantageous for identification of pathogens. To assess the value of mNGS using pus in patients with sepsis, thirty-five samples were collected. Pathogen identification and mixed infection diagnosis obtained by use of mNGS or cultivation methods were compared. Fifty-three aerobic or facultative anaerobes, 59 obligate anaerobes and 7 fungi were identified by the two methods. mNGS increased the accuracy rate of diagnosing aerobic or facultative anaerobic infections from 44.4% to 94.4%; mNGS also increased the sensitivity of diagnosing obligate anaerobic infections from 52.9% to 100.0%; however, mNGS did not show any advantage in terms of fungal infections. Culture and mNGS identified 1 and 24 patients with mixed infection, respectively. For obligate anaerobes, source of microorganisms was analyzed. The odontogenic bacteria all caused empyema (n = 7) or skin and soft tissue infections (n = 5), whereas the gut-derived microbes all caused intra-abdominal infections (n = 7). We also compared the clinical characteristics of non-obligate anaerobic and obligate anaerobic infection groups. The SOFA score [9.0 (7.5, 14.3) vs. 5.0 (3.0, 8.0), P = 0.005], procalcitonin value [4.7 (1.8, 39.9) vs. 2.50 (0.7, 8.0), P = 0.035], the proportion of septic shock (66.7% vs. 35.3%, P = 0.044) and acute liver injury (66.7% vs. 23.5%, P = 0.018) in the non-obligate anaerobic infection group were significantly higher than those in the obligate anaerobic infection group. In patients with sepsis caused by purulent infection, mNGS using pus from the primary lesion may yield more valuable microbiological information.

12.
Front Immunol ; 15: 1339373, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38318171

RESUMEN

Background: Diabetes mellitus is a significant health problem worldwide, often leading to diabetic kidney disease (DKD), which may also influence the occurrence of hepatocellular carcinoma (HCC). However, the relationship and diagnostic biomarkers between DKD and HCC are unclear. Methods: Using public database data, we screened DKD secretory RNAs and HCC essential genes by limma and WGCNA. Potential mechanisms, drugs, and biomarkers for DKD-associated HCC were identified using PPI, functional enrichment, cMAP, and machine learning algorithms, and a diagnostic nomogram was constructed. Then, ROC, calibration, and decision curves were used to evaluate the diagnostic performance of the nomograms. In addition, immune cell infiltration in HCC was explored using CIBERSORT. Finally, the detectability of critical genes in blood was verified by qPCR. Results: 104 DEGs associated with HCC using WGCNA were identified. 101 DEGs from DKD were predicated on secreting into the bloodstream with Exorbase datasets. PPI analysis identified three critical modules considered causative genes for DKD-associated HCC, primarily involved in inflammation and immune regulation. Using lasso and RM, four hub genes associated with DKD-associated HCC were identified, and a diagnostic nomogram confirmed by DCA curves was established. The results of immune cell infiltration showed immune dysregulation in HCC, which was associated with the expression of four essential genes. PLVAP was validated by qPCR as a possible blood-based diagnostic marker for DKD-related HCC. Conclusion: We revealed the inflammatory immune pathways of DKD-related HCC and developed a diagnostic nomogram for HCC based on PLVAP, C7, COL15A1, and MS4A6A. We confirmed with qPCR that PLVAP can be used as a blood marker to assess the risk of HCC in DKD patients.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/etiología , Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/etiología , Neoplasias Hepáticas/genética , Algoritmos , Biomarcadores , Aprendizaje Automático
13.
Mater Today Bio ; 24: 100944, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38269056

RESUMEN

Corneal neovascularization (CNV) is a heavy attribute of blinding disease changes. Existing medications need numerous infusions and have a limited absorption. Investigating novel drugs with safety, efficacy, and convenience is crucial. In this study, we developed a bone morphogenetic protein 4 (BMP4)-loaded poloxamer-oxidized sodium alginate (F127-OSA) thermosensitive hydrogel. The 14 % F127-OSA hydrogel transformed from sol to gel at 31-32 °C, which might extend the application period on the ocular surface. The hydrogel's porous structure and uniform dispersion made it possible for drugs to release gradually. We used a suture-induced rat CNV model to investigate the mechanism of CNV inhibition by hydrogel. We discovered that F127-OSA hydrogel loaded with BMP4 could significantly reduce the length and area of CNV, relieve corneal edema, and stop aberrant epithelial cell proliferation. The hydrogel's efficacy was superior to that of the common solvent group. Additionally, BMP4 thermosensitive hydrogel repaired ultrastructure, including microvilli, intercellular junctions, and damaged apical junctional complexes (AJCs), suggesting a potential mechanism by which the hydrogel prevented CNV formation. In conclusion, our investigation demonstrates that F127-OSA thermosensitive hydrogel loaded with BMP4 can repair corneal epithelial AJCs and is a promising novel medication for the treatment of CNV.

14.
J Agric Food Chem ; 72(5): 2741-2755, 2024 Feb 07.
Artículo en Inglés | MEDLINE | ID: mdl-38284775

RESUMEN

Aflatoxin B1 (AFB1) is one of the most harmful and toxic mycotoxins in foods and feeds, posing a serious health risk to both humans and animals, especially its hepatotoxicity. Nuclear factor-erythroid 2-related factor 2 (Nrf2), an important nuclear transcription factor, is generally recognized as a potential target for phytochemicals to ameliorate liver injury. The current study sought to elucidate the molecular processes by which licochalcone A (Lico A), a compound derived from Xinjiang licorice Glycyrrhiza inflate, protects against AFB1 toxicity. In vivo, male wild-type (WT) and Nrf2 knockout (Nrf2-/-) C57BL/6 mice were orally administered AFB1 at 1.5 mg/kg body weight (BW) with or without Lico A at 5 mg/kg. In vitro, AML12 cells were utilized to evaluate the protective effect and mechanism of Lico A against the AFB1-induced hepatotoxicity. Our findings demonstrated that AFB1 caused severe hepatotoxicity, while Lico A treatment successfully relieved the toxicity. Meanwhile, Lico A effectively improved liver injury, inflammatory mediators, oxidative insults, apoptosis, liver fibrosis, and pyroptosis, which contributed to the inhibition of toll receptor 4 (TLR4)-NF-κB/MAPK and NOD-like receptors protein 3 (NLRP3)/caspase-1/GSDMD signaling pathway activation. Furthermore, Lico A was able to enhance the Nrf2 antioxidant signaling pathway. Intriguingly, Lico A still had a protective effect on AFB1-caused liver injury in mice via the inhibition of inflammation and pyroptosis, while apoptosis and liver fibrosis were blocked in the absence of Nrf2. To sum up, the present study first elucidated that Lico A ameliorated AFB1-induced hepatotoxic effects and its main mechanism involved the inhibitory effects on oxidative stress, apoptosis, liver fibrosis, inflammation, and pyroptosis, which might be partially dependent on the regulation of Nrf2. The work may enrich the role and mechanism of Lico A's resistance to liver injury caused by various factors, and its application is promising.


Asunto(s)
Chalconas , Enfermedad Hepática Inducida por Sustancias y Drogas , Factor 2 Relacionado con NF-E2 , Humanos , Masculino , Animales , Ratones , Factor 2 Relacionado con NF-E2/metabolismo , Aflatoxina B1/toxicidad , Ratones Endogámicos C57BL , Transducción de Señal , Estrés Oxidativo , Inflamación/metabolismo , Hígado/metabolismo , Enfermedad Hepática Inducida por Sustancias y Drogas/metabolismo , Cirrosis Hepática/metabolismo
15.
Exp Eye Res ; 237: 109680, 2023 12.
Artículo en Inglés | MEDLINE | ID: mdl-37858608

RESUMEN

Corneal neovascularization (CNV) can lead to impaired corneal transparency, resulting in vision loss or blindness. The primary pathological mechanism underlying CNV is an imbalance between pro-angiogenic and anti-angiogenic factors, with inflammation playing a crucial role. Notably, a vascular endothelial growth factor(VEGF)-A gradient triggers the selection of single endothelial cells(ECs) into primary tip cells that guide sprouting, while a dynamic balance between tip and stalk cells maintains a specific ratio to promote CNV. Despite the central importance of tip-stalk cell selection and shuffling, the underlying mechanisms remain poorly understood. In this study, we examined the effects of bone morphogenetic protein 4 (BMP4) on VEGF-A-induced lumen formation in human umbilical vein endothelial cells (HUVECs) and CD34-stained tip cell formation. In vivo, BMP4 inhibited CNV caused by corneal sutures. This process was achieved by BMP4 decreasing the protein expression of VEGF-A and VEGFR2 in corneal tissue after corneal suture injury. By observing the ultrastructure of the cornea, BMP4 inhibited the sprouting of tip cells and brought forward the appearance of intussusception. Meanwhile, BMP4 attenuated the inflammatory response by inhibiting neutrophil extracellular traps (NETs)formation through the NADPH oxidase-2(NOX-2)pathway. Our results indicate that BMP4 inhibits the formation of tip cells by reducing the generation of NETs, disrupting the dynamic balance of tip and stalk cells and thereby inhibiting CNV, suggesting that BMP4 may be a potential therapeutic target for CNV.


Asunto(s)
Lesiones de la Cornea , Neovascularización de la Córnea , Humanos , Neovascularización de la Córnea/metabolismo , Proteína Morfogenética Ósea 4/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismo , Córnea/metabolismo , Células Endoteliales de la Vena Umbilical Humana/patología , Lesiones de la Cornea/metabolismo , Neovascularización Fisiológica
16.
Infect Drug Resist ; 16: 6309-6322, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37780531

RESUMEN

Objective: To evaluate the diagnostic value and clinical application of metagenomic next-generation sequencing (mNGS) for infections in critically ill patients. Methods: Comparison of diagnostic performance of mNGS and conventional microbiological testing for pathogens was analyzed in 234 patients. The differences between immunocompetent and immunocompromised individuals in mNGS-guided anti-infective treatment adjustment were also analyzed. Results: The sensitivity and specificity of mNGS for bacterial and fungal detection were 96.6% (95% confidence interval [CI], 93.5%-99.6%) and 83.1% (95% CI, 75.2%-91.1%), and 85.7% (95% CI, 71.9%-99.5%) and 93.2% (95% CI, 89.7%-96.7%), respectively. Overall, 152 viruses were detected by mNGS, but in which 28 viruses were considered causative agents. The proportion of mNGS-guided beneficial anti-infective therapy adjustments in the immunocompromised group was greater than in the immunocompetent group (48.5% vs 30.1%; P=0.008). In addition, mNGS-guided anti-infective regimens with peripheral blood and BALF specimens had the highest proportion (39.0%; 40.0%), but the proportion of patients not helpful due to peripheral blood mNGS was also as high as 22.0%. Conclusion: mNGS might be a promising technology to provide precision medicine for critically ill patients with infection.

17.
Pharmacol Res ; 197: 106946, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37797661

RESUMEN

Ocular neovascular disease (OND), characterized by the aberrant formation of immature blood vessels, is the leading cause of vision impairment and blindness. It is important to find effective ways to diagnose and treat these diseases. Circular RNA (circRNA) is a group of endogenous non-coding RNA that play a crucial role in regulating different biological processes. Due to their close association with ocular disease and angiogenesis, circRNAs have become a hotspot in OND research. In this review, we intensively investigate the possibility of using circRNAs in the management of ONDs. In general, angiogenesis is divided into five phases. On the basis of these five steps, we describe the potential of using circRNAs by introducing how they regulate angiogenesis. Subsequently, the interactions between circRNAs and ONDs, including pterygium, corneal neovascularization, age-related macular degeneration, diabetic retinopathy, and retinopathy of prematurity, are analyzed in detail. We also introduce the potential use of circRNAs as OND diagnostic biomarkers. Finally, we summarize the prospects of using circRNAs as a potential strategy in OND management. The gaps in recent research are also pointed out with the purpose of promoting the introduction of circRNAs into clinical applications.


Asunto(s)
Retinopatía Diabética , Degeneración Macular , Enfermedades de la Retina , Humanos , Recién Nacido , ARN Circular/genética , Ojo , Retinopatía Diabética/genética
18.
Front Physiol ; 14: 1234104, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37601629

RESUMEN

Vascular endothelial (VE)-cadherin, an endothelium-specific adhesion protein, is found in the junctions between endothelial cells (ECs). It's crucial to maintain the homogeneity of ECs. Keeping and controlling the contact between ECs is essential. In addition to its adhesive function, VE-cadherin plays important roles in vascular development, permeability, and tumour angiogenesis. Signal transfer, cytoskeletal reconstruction, and contractile integrating, which are crucial for constructing and maintaining monolayer integrity as well as for repair and regeneration, are the foundation of endothelial cell (EC) junctional dynamics. The molecular basis of adhesion junctions (AJs), which are closely related and work with actin filaments, is provided by the VE-cadherin-catenin complex. They can activate intracellular signals that drive ECs to react or communicate structural changes to junctions. An increasing number of molecules, including the vascular endothelial growth factor receptor 2 (VEGFR2) and vascular endothelial protein tyrosine phosphatase (VE-PTP), have been connected to VE-cadherin in addition to the conventional VE-cadherin-catenin complex. This review demonstrates significant progress in our understanding of the molecular mechanisms that affect VE-cadherin's function in the regulation of EC behaviour during angiogenesis. The knowledge of the molecular processes that control VE-cadherin's role in the regulation of EC behaviour during angiogenesis has recently advanced, as shown in this review.

19.
Artículo en Inglés | MEDLINE | ID: mdl-37605422

RESUMEN

BACKGROUND: Limbal stem cells (LSCs) are essential for maintaining corneal transparency and ocular surface integrity. Many external factors or genetic diseases can lead to corneal limbal stem cell deficiency (LSCD), resulting in the loss of barrier and corneal epithelial cell renewal functions. Stem cell transplantation is one of the primary treatments for LSCD, including limbal transplantation and cultivated limbal epithelial transplantation. In addition, a variety of non-limbal stem cell lines have been experimented with for LSCD treatment. Biological scaffolds are also used to support in vitro stem cell culture and transplantation. Here, we review the mechanisms of corneal maintenance by LSCs, the clinical stage and surgical treatment of LSCD, the source of stem cells, and the biological scaffolds required for in vitro culture. METHODS: This study is a narrative retrospective study aimed at collecting available information on various aspects of surgical treatments for LSCD. Relevant literature was searched in a range of online databases, including Web of Science, Scopus, and PubMed from 2005 to March, 2023. RESULTS: A total of 397 relevant articles were found, and 49 articles with strong relevance to the studies in this paper were obtained and analyzed. Moreover, 11 of these articles were on the concept of LSCD and the mechanism of LESCs maintaining the corneal epithelium, 3 articles on the staging and grading of LSCD, 17 articles on cell transplantation methods and donor cell sources, and 18 articles on scaffolds for delivering stem cells. We also summarized the advantages and disadvantages of different cell transplantation methods and the benefits and limitations of scaffolds based on the above literature. CONCLUSION: The treatment of LSCD is determined by the clinical stage and whether it involves monocular or binocular eyes. Appropriate surgical techniques should be taken for LSCD patients in order to reconstruct the ocular surface, relieve symptoms, and restore visual function. Meanwhile, biological scaffolds assist in the ex vivo culture and implantation of stem cells.

20.
Indian J Ophthalmol ; 71(6): 2369-2378, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-37322646

RESUMEN

Although corneal refractive surgery has been proven to be excellent in terms of safety and effectiveness, the reduction of postoperative corneal ectasia remains one of the most concerned topics for surgeons. Forme fruste keratoconus (FFKC) is the most important factor that leads to postoperative corneal ectasia, and common preoperative screenings of the condition include corneal morphology examination and corneal biomechanical examination. However, there are limitations to the single morphological examination or biomechanical examination, and the advantages of the combination of the two have been gradually emerging. The combined examination is more accurate in the diagnosis of FFKC and can provide a basis for determining suspected keratoconus. It allows one to measure the true intraocular pressure (IOP) before and after surgery and is recommended for older patients and those with allergic conjunctivitis. This article aims to discuss the application, advantages, and disadvantages of single examination and combined examination in the preoperative screening of refractive surgery, so as to provide a certain reference value for choosing suitable patients for surgery, improving surgical safety, and reducing the risk of postoperative ectasia.


Asunto(s)
Queratocono , Humanos , Queratocono/diagnóstico , Queratocono/cirugía , Topografía de la Córnea , Dilatación Patológica , Córnea/cirugía , Queratoplastia Penetrante , Fenómenos Biomecánicos
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