Comprehensive macro and micro views on immune cells in ischemic heart disease.

Ischemic heart disease (IHD) is a prevalent cardiovascular condition that remains the primary cause of death due to its adverse ventricular remodelling and pathological changes in end-stage heart failure. As a complex pathologic condition, it involves intricate regulatory processes at the cellular and molecular levels. The immune system and cardiovascular system are closely interconnected, with immune cells playing a crucial role in maintaining cardiac health and influencing disease progression. Consequently, alterations in the cardiac microenvironment are influenced and controlled by various immune cells, such as macrophages, neutrophils, dendritic cells, eosinophils, and T-lymphocytes, along with the cytokines they produce. Furthermore, studies have revealed that Gata6+ pericardial cavity macrophages play a key role in regulating immune cell migration and subsequent myocardial tissue repair post IHD onset. This review outlines the role of immune cells in orchestrating inflammatory responses and facilitating myocardial repair following IHD, considering both macro and micro views. It also discusses innovative immune cell-based therapeutic strategies, offering new insights for further research on the pathophysiology of ischemic heart disease and immune cell-targeted therapy for IHD.

Corosolic acid attenuates cardiac ischemia/reperfusion injury through the PHB2/PINK1/parkin/mitophagy pathway.

Despite advances in treatment, myocardial infarction remains the leading cause of heart failure and death worldwide, and the restoration of coronary blood flow can also cause heart damage. In this study, we found that corosolic acid (CA), also known as plant insulin, significantly protects the heart from ischemia-reperfusion (I/R) injury. In addition, CA can inhibit oxidative stress and improve mitochondrial structure and function in cardiomyocytes. Subsequently, our study demonstrated that CA improved the expression of the mitophagy-related proteins Prohibitin 2 (PHB2), PTEN-induced putative kinase protein-1 (PINK1), and Parkin. Meanwhile, through molecular docking, we found an excellent binding between CA and PHB2 protein. Finally, the knockdown of PHB2 eliminated the protective effect of CA on hypoxia-reoxygenation in cardiomyocytes. Taken together, our study reveals that CA increases mitophagy in cardiomyocytes via the PHB2/PINK1/Parkin signaling pathway, inhibits oxidative stress response, and maintains mitochondrial function, thereby improving cardiac function after I/R.

A novel clinical prediction model for in-hospital mortality in sepsis patients complicated by ARDS: A MIMIC IV database and external validation study.

Background: Sepsis complicated by ARDS significantly increases morbidity and mortality, underscoring the need for robust predictive models to enhance patient management. Methods: We collected data on 6390 patients with ARDS-complicated sepsis from the MIMIC IV database. Following rigorous data cleaning, including outlier management, handling missing values, and transforming variables, we conducted univariate analysis and logistic multivariate regression. We employed the LASSO machine learning algorithm to identify risk factors closely associated with patient outcomes. These factors were then used to develop a new clinical prediction model. The model underwent preliminary assessment and internal validation, and its performance was further tested through external validation using data from 225 patients at a major tertiary hospital in China. This validation assessed the model's discrimination, calibration, and net clinical benefits. Results: The model, illustrated by a concise nomogram, demonstrated significant discrimination with an area under the curve (AUC) of 0.711 in the internal validation set and 0.771 in the external validation set, outperforming conventional severity scores such as the SOFA and SAPS II. It also showed good calibration and net clinical benefits. Conclusions: Our model serves as a valuable tool for identifying sepsis patients with ARDS at high risk of in-hospital mortality. This could enable the implementation of personalized treatment strategies, potentially improving patient outcomes.

Discussion on the relationship between gut microbiota and glioma through Mendelian randomization test based on the brain gut axis.

BACKGROUND: In the realm of Gut-Brain axis research, existing evidence points to a complex bidirectional regulatory mechanism between gut microbiota and the brain. However, the question of whether a causal relationship exists between gut microbiota and specific types of brain tumors, such as gliomas, remains unresolved. To address this gap, we employed publicly available Genome-Wide Association Study (GWAS) and MIOBEN databases, conducting an in-depth analysis using Two-Sample Mendelian Randomization (MR). METHOD: We carried out two sets of MR analyses. The preliminary analysis included fewer instrumental variables due to a high genome-wide statistical significance threshold (5×10-8). To enable a more comprehensive and detailed analysis, we adjusted the significance threshold to 1×10-5. We performed linkage disequilibrium analysis (R2 <0.001, clumping distance = 10,000kb) and detailed screening of palindromic SNPs, followed by MR analysis and validation through sensitivity analysis. RESULTS: Our findings reveal a causal relationship between gut microbiota and gliomas. Further confirmation via Inverse Variance Weighting (IVW) identified eight specific microbial communities related to gliomas. Notably, the Peptostreptococcaceae and Olsenella communities appear to have a protective effect, reducing glioma risk. CONCLUSION: This study not only confirms the causal link between gut microbiota and gliomas but also suggests a new avenue for future glioma treatment.

Comprehensive view of macrophage autophagy and its application in cardiovascular diseases.

Cardiovascular diseases (CVDs) are the primary drivers of the growing public health epidemic and the leading cause of premature mortality and economic burden worldwide. With decades of research, CVDs have been proven to be associated with the dysregulation of the inflammatory response, with macrophages playing imperative roles in influencing the prognosis of CVDs. Autophagy is a conserved pathway that maintains cellular functions. Emerging evidence has revealed an intrinsic connection between autophagy and macrophage functions. This review focuses on the role and underlying mechanisms of autophagy-mediated regulation of macrophage plasticity in polarization, inflammasome activation, cytokine secretion, metabolism, phagocytosis, and the number of macrophages. In addition, autophagy has been shown to connect macrophages and heart cells. It is attributed to specific substrate degradation or signalling pathway activation by autophagy-related proteins. Referring to the latest reports, applications targeting macrophage autophagy have been discussed in CVDs, such as atherosclerosis, myocardial infarction, heart failure, and myocarditis. This review describes a novel approach for future CVD therapies.

Elevated tissue transglutaminase levels in aqueous humor of congenital cataractous eyes with long axial length.

Objective: To investigate the distribution of axial length (AL) and posterior staphyloma (PS) in congenital cataract (CC) patients. The correlation between AL and the concentration of tissue transglutaminase (TGM2) in the aqueous humor (AH) of cataractous eyes was also evaluated. Methods: Cross-sectional data were collected from 499 children with CC who underwent phacoemulsification, anterior vitrectomy, and IOL implantation. AL measured by IOLMaster or A-scan ultrasonography and the presence of PS examined by B-scan ultrasonography were recorded. TGM2 levels in AH of 15 CC patients with normal axial length (NAL) and 15 CC patients with PS or long axial length (LAL) were measured by enzyme-linked immunosorbent assay. Results: The presence of PS in congenital cataractous eyes was 11.02%, and the presence of PS + LAL in congenital cataractous eyes was 29.06%. The AH levels of TGM2 in the cataractous group with NAL were lower than those in the cataractous group with PS or LAL (P < 0.001). The concentration of TGM2 in AH were positively correlated with AL of the patients' eyes (P = 0.001). Additionally, we found that TGM2 expressed in the cytoplasm of lens epithelial cells of cataractous eyes, and the expression level increased with the AL value. Conclusions: This study begins to lay the groundwork for investigating the characteristics of PS and LAL in patients with CC. Furthermore, AL was positively correlated with AH levels of TGM2.

Surgical Outcomes of Lensectomy-Vitrectomy with Primary Intraocular Lens Implantation in Children with Bilateral Congenital Cataracts.

In this study, we evaluated the long-term surgical outcomes of lensectomy-vitrectomy with primary intraocular lens (IOL) implantation in children with bilateral congenital cataracts (CCs) and investigated the potential risk factors for low vision. A total of 148 eyes in 74 children who underwent lensectomy-vitrectomy with primary IOL implantation were enrolled in this study. The surgery age was 44.04 ± 14.60 months, with a follow-up period of 46.66 ± 14.34 months. The final BCVA was 0.24 ± 0.32 logMAR, and low vision was found in 22 eyes (14.9%). Postoperative complications requiring additional surgeries included VAO (4 eyes, 5.4%), IOL pupillary captures (2 eyes, 2.0%), iris incarceration (1 eye, 0.7%), and glaucoma (1 eye, 0.7%). A higher incidence of VAO and larger postoperative refractive error was observed in younger children (≤2 years old) than in elder children (>2 years old) (p = 0.003, p = 0.047, respectively). Final BCVA was affected by preexisting comorbidity (p < 0.001), cataract density (p < 0.001), cataract size (p = 0.020), occurrence of postoperative complications (p = 0.011), and ASE (p = 0.008). Multivariate analysis showed that denser cataracts (OR = 9.303, p = 0.035) and preexisting comorbidity (OR = 4.712, p = 0.004) were the significant predictors of low vision. In conclusion, lensectomy-vitrectomy with primary IOL implantation is an effective and safe treatment for CC. The long-term visual outcome is encouraging in children with bilateral CC undergoing this procedure with a low rate of postoperative complications requiring surgeries. Moreover, eyes with denser cataracts and preexisting comorbidity may have a high risk of low vision.

Glutathione system enhancement for cardiac protection: pharmacological options against oxidative stress and ferroptosis.

The glutathione (GSH) system is considered to be one of the most powerful endogenous antioxidant systems in the cardiovascular system due to its key contribution to detoxifying xenobiotics and scavenging overreactive oxygen species (ROS). Numerous investigations have suggested that disruption of the GSH system is a critical element in the pathogenesis of myocardial injury. Meanwhile, a newly proposed type of cell death, ferroptosis, has been demonstrated to be closely related to the GSH system, which affects the process and outcome of myocardial injury. Moreover, in facing various pathological challenges, the mammalian heart, which possesses high levels of mitochondria and weak antioxidant capacity, is susceptible to oxidant production and oxidative damage. Therefore, targeted enhancement of the GSH system along with prevention of ferroptosis in the myocardium is a promising therapeutic strategy. In this review, we first systematically describe the physiological functions and anabolism of the GSH system, as well as its effects on cardiac injury. Then, we discuss the relationship between the GSH system and ferroptosis in myocardial injury. Moreover, a comprehensive summary of the activation strategies of the GSH system is presented, where we mainly identify several promising herbal monomers, which may provide valuable guidelines for the exploration of new therapeutic approaches.

TGF-ß/Smad Signalling Activation by HTRA1 Regulates the Function of Human Lens Epithelial Cells and Its Mechanism in Posterior Subcapsular Congenital Cataract.

Congenital cataract is the leading cause of blindness among children worldwide. Patients with posterior subcapsular congenital cataract (PSC) in the central visual axis can result in worsening vision and stimulus deprivation amblyopia. However, the pathogenesis of PSC remains unclear. This study aims to explore the functional regulation and mechanism of HTRA1 in human lens epithelial cells (HLECs). HTRA1 was significantly downregulated in the lens capsules of children with PSC compared to normal controls. HTRA1 is a suppression factor of transforming growth factor-ß (TGF-ß) signalling pathway, which plays a key role in cataract formation. The results showed that the TGF-ß/Smad signalling pathway was activated in the lens tissue of PSC. The effect of HTRA1 on cell proliferation, migration and apoptosis was measured in HLECs. In primary HLECs, the downregulation of HTRA1 can promote the proliferation and migration of HLECs by activating the TGF-ß/Smad signalling pathway and can significantly upregulate the TGF-ß/Smad downstream target genes FN1 and α-SMA. HTRA1 was also knocked out in the eyes of C57BL/6J mice via adeno-associated virus-mediated RNA interference. The results showed that HTRA1 knockout can significantly upregulate p-Smad2/3 and activate the TGF-ß/Smad signalling pathway, resulting in abnormal proliferation and irregular arrangement of lens epithelial cells and leading to the occurrence of subcapsular cataract. To conclude, HTRA1 was significantly downregulated in children with PSC, and the downregulation of HTRA1 enhanced the proliferation and migration of HLECs by activating the TGF-ß/Smad signalling pathway, which led to the occurrence of PSC.

Acetyl-11-Keto-Beta Boswellic Acid (AKBA) Protects Lens Epithelial Cells Against H2O2-Induced Oxidative Injury and Attenuates Cataract Progression by Activating Keap1/Nrf2/HO-1 Signaling.

Age-related cataract (ARC) is one of the leading blinding eye diseases worldwide. Chronic oxidative stress and the apoptosis of human lens epithelial cells (HLECs) have been suggested to be the mechanism underlying cataract formation. Acetyl-11-keto-ß-boswellic acid (AKBA) is a pentacyclic triterpene with antioxidative and antiapoptotic effects. In this study, we investigated the potential effects of AKBA on oxidative-induced HLECs injury and cataract formation. H2O2 was used to simulate HLECs oxidative injury in vitro, and Na2SeO3 was applied to establish an in vivo cataract model. In our current study, a cell counting kit-8 (CCK-8) assay was performed to evaluate the effects of H2O2 and AKBA on cell viability in vitro. Intracellular reactive oxygen species (ROS) levels were measured with the ROS assay to verify the antioxidant capacity of AKBA. Apoptotic cells were detected and measured by TUNEL staining and flow cytometry, and quantitative real-time (qRT)-PCR and Western blotting were applied to examine the transcription and expression of apoptosis-related proteins. Furthermore, immunofluorescence staining was performed to locate factor-erythroid 2-related factor 2 (Nrf2), and the protein levels of Nrf2, kelch-like ECH-associated protein 1 (Keap1) and heme oxygenase-1 (HO-1) were determined by Western blotting. Finally, we observed the degree of lens opacity and performed hematoxylin-eosin (H&E) staining to assess the protective effect of AKBA on cataract formation in vivo. AKBA increased HLECs viability under H2O2 stimulation, decreased intracellular ROS levels and alleviated the cell apoptosis rate in vitro. AKBA significantly decreased the expression of caspase-3 and Bax and increased the content of Bcl-2. The results of immunofluorescence and immunohistochemical staining proved that the expression and nuclear translocation of Nrf2 were activated with AKBA treatment in vivo and in vitro. Moreover, computational docking results showed that AKBA could bind specifically to the predicted Keap1/Nrf2 binding sites. After AKBA activation, Nrf2 dissociates from the Nrf2/Keap1 complex, translocates into the nucleus, and subsequently promotes HO-1 expression. In addition, AKBA attenuated lens opacity in selenite-induced cataracts. Overall, these findings indicated that AKBA alleviated oxidative injury and cataract formation by activating the Keap1/Nrf2/HO-1 cascade. Therefore, our current study highlights that AKBA may serve as a promising treatment for ARC progression.

Effect of bilateral inferior oblique partial myectomy on V pattern exotropia with inferior oblique overaction.

PURPOSE: To compare the effect of bilateral inferior oblique partial myectomy on V-pattern exotropia patients with bilateral symmetric inferior oblique overaction (IOOA) and asymmetric IOOA. METHODS: This was a retrospective study including 53 V-pattern exotropia patients with bilateral IOOA of all grades who underwent bilateral inferior oblique partial myectomy. Success was defined as the elimination of the IOOA and the collapse of the V pattern at the final follow-up. The fovea-disc angle (FDA) and V-pattern exotropia were compared before and after surgery. RESULTS: This study included 53 V-pattern exotropia patients, containing 29 patients with symmetric IOOA (Group I) and 24 patients with asymmetric IOOA (Group II). The last follow-up ranged from 3 to 16 months (mean of 5 months). After myectomy, 3 eyes in Group I and 2 eyes in Group II were observed with residual grade 1 IOOA. The surgical success rates of IOOA correction in Group I and Group II were 96% and 95%, respectively. The difference was not statistically significant (P = 0.808). V-pattern exotropia collapsed with residual 2 (min. 0, max. 6) PD for Group I and 2 (min. 0, max. 10) PD for Group II, and there was a statistically significant difference between pre- and postoperative V-pattern exotropia in the two groups (P = 0.000). No inferior oblique (IO) underaction or antielevation syndrome (AES) was found in either group. The average preoperative FDA of the right eye and the left eye was (8.93 ± 4.34)° and (10.86 ± 4.27)° in Group I and (9.08 ± 4.92)° and (11.00 ± 5.69)° in Group II. There was a significant difference in preoperative FDA between the right eye and the left eye in the two groups (Group I p = 0.029; Group II p = 0.038). CONCLUSIONS: Bilateral inferior oblique partial myectomy can bring "symmetric" effectiveness in the correction of IOOA and FDA. It can potentially be used as a safe and successful treatment for V-pattern exotropia with bilateral IOOA. In addition, the FDA may be a promising index for evaluating fundus extorsion.

The influence of congenital and developmental cataract surgery on the ocular surface in a six-month follow-up prospective clinical study.

BACKGROUND: The purpose of this study was to identify changes in tear film function and meibomian gland function in children after congenital/developmental cataract surgery. METHODS: This study enrolled 16 eyes of 16 congenital/developmental cataract patients (mean age: 8.05 ± 1.43 years) who underwent cataract surgery and 16 eyes of 16 normal volunteers (mean age: 8.31 ± 2.18 years). Clinical assessments were conducted preoperatively and at 1 week, 1, 3 and 6 months postoperatively. Symptom questionnaires, non-invasive tear film break-up time, tear meniscus height, corneal fluorescein staining, lid margin abnormality, meibomian gland expressibility, and meibography were assessed. RESULTS: The ocular symptom score was significantly higher in congenital/developmental cataract patients compared to normal controls during the 5 visits (P = 0.009). And the average non-invasive tear film break-up time was significantly lower in congenital/developmental cataract patients compared to normal controls (P = 0.017). The first non-invasive tear film break-up time and average non-invasive tear film break-up time were lowest at 1 month postoperatively compared to baseline levels (P = 0.008 and P = 0.012, respectively). The lid margin score of the upper eyelid was significantly higher in congenital/developmental cataract patients compared to normal controls at 1 week postoperatively (P = 0.027). The meibum expressibility score decreased significantly during the 5 visits (P = 0.024). No significant difference was observed in meibomian gland tortuosity, meibomian gland width, meibomian gland area and meibomian gland length between the congenital/developmental group and normal controls preoperatively and at 6 months postoperatively (P > 0.05). CONCLUSION: Tear film stability and meibomian gland function are worsened transiently after congenital/developmental cataract surgery without accompanying meibomian gland morphological changes.

The impact of pre-operative axial length on myopic shift 3 years after congenital and developmental cataract surgery and intraocular lens implantation.

Purpose: To investigate the impact of the pre-operative axial length (AL) on myopic shift (MS) 3 years after primary intraocular lens (IOL) implantation in congenital/developmental cataract patients. Methods: A retrospective study of patients who underwent congenital/developmental cataract surgery and primary IOL implantation at age 2-3 years at EENT Hospital was conducted. All patients were followed up regularly for at least 3 years after surgery. Refractive outcomes, including spherical equivalent (SE) and MS, were collected at each follow-up. Results: Forty eyes from 40 patients were included. The mean age at surgery was 2.56 ± 0.57 years old, and the mean follow-up time was 3.05 ± 0.22 years. Patients were divided into two groups: Group 1 included 20 patients with longer pre-operative ALs (≥22 mm), and Group 2 included 20 patients with average pre-operative ALs (<22 mm). By the last follow-up, the MS was 2.13 (0.38, 2.63) D in Group 1 and 3.88 (2.85, 5.72) D in Group 2. The post-operative MS in Group 2 was statistically greater than that in Group 1 at 3 years after surgery (P < 0.001). Conclusion: In congenital/developmental cataract patients who underwent cataract extraction and primary IOL implantation at age 2-3 years, eyes with longer pre-operative ALs had a slower MS than those with average pre-operative ALs 3 years after surgery. This finding could have implications for the target refraction decision in congenital/developmental cataract surgery.

Transcriptomics Analysis of Lens from Patients with Posterior Subcapsular Congenital Cataract.

To gain insight into the aetiology of posterior subcapsular congenital cataract from the perspective of transcriptional changes, we conducted an mRNA sequencing analysis of the lenses in posterior subcapsular congenital cataract patients and in normal children. There were 1533 differentially expressed genes from 19,072 genes in the lens epithelial cells of the posterior subcapsular congenital cataract patients compared to in the normal controls at a cut-off criteria of |log2 fold change| of >1 and a p-value of <0.05, including 847 downregulated genes and 686 upregulated genes. To further narrow down the DEGs, we utilised the stricter criteria of |log2 fold change| of >1 and an FDR value of <0.05, and we identified 551 DEGs, including 97 upregulated genes and 454 downregulated genes. This study also identified 1263 differentially expressed genes of the 18,755 genes in lens cortex and nuclear fibres, including 646 downregulated genes and 617 upregulated genes. The downregulated genes in epithelial cells were significantly enriched in the structural constituent of lenses, lens development and lens fibre cell differentiation. After filtering the DEGs using the databases iSyTE and Cat-Map, several high-priority candidate genes related to posterior subcapsular congenital cataract such as GRIFIN, HTRA1 and DAPL1 were identified. The findings of our study may provide a deeper understanding of the mechanisms of posterior subcapsular congenital cataract and help in the prevention and treatment of this disease.

Effects of Cigarette Smoking on Retinal and Choroidal Thickness: A Systematic Review and Meta-Analysis.

BACKGROUND: Cigarette smoking has been regarded as a risk factor for the incidence of a wide variety of chronic illness; however, its effect on thickness of the retina or choroid is still unknown. METHODS: A consummate literature search was conducted in PubMed and Embase up to January, 2018. The quantitative synthesis was conducted by Stata 12.0. RESULTS: A total of 13 observational studies were included in this meta-analysis. In this meta-analysis of all available observational studies, no significant effect of tobacco smoking on retinal or choroidal thickness change was detected. However, advanced analyses showed that smoking would influence the thickness of RNFL (average: SMD, -0.332; 95% CI, -0.637 to -0.027; inferior: SMD, -0.632; 95% CI, -1.092 to -0.172; and superior: SMD, -0.720; 95% CI, -0.977 to -0.463) and GCL (superior: SMD, -0.549; 95% CI, -0.884 to -0.215; inferior: SMD, -0.602; 95% CI, -0.938 to -0.265). Meanwhile, subgroup analyses demonstrated that the results based on studies in some regions (America and Africa) and cross-sectional studies showed a reduced choroidal thickness in smokers. No publication bias was detected in this study. CONCLUSION: In conclusion, no significant effect of tobacco smoking on retinal or choroidal thickness change was detected. However, smoking would influence the thickness of RNFL and GCL. Future research on this field would help in the prevention and treatment of smoking-associated disorders.

Involvement of dysregulated coding and long non­coding RNAs in the pathogenesis of strabismus.

Strabismus is a common ocular disorder in children and may result in exterior abnormalities and impaired visual functions. However, the detailed pathogenesis of strabismus unclear. The present study assessed the comprehensive analyses on the roles of RNAs in the development of strabismus. The public datasets of strabismus and the corresponding control tissues were downloaded from the Gene Expression Omnibus (GEO). Reannotations of the dysregulated coding and long non­coding RNAs (lncRNAs) and functional enrichments of the differently expressed genes (DEGs) were conducted. A total of 790 DEGs were screened (648 upregulated and 142 downregulated) in the present study. Among the DEGs, a total of 32 differently expressed lncRNAs were detected (14 upregulated and 18 downregulated). When the Gene Ontology (GO) enrichment was considered, it was identified that a total of 143 GO terms (82 for biological process, 31 for cellular component and 30 for molecular function) were identified. Among all the 57 detected Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, the phagosome pathway, which was labeled as hsa004145, demonstrated the most bioinformatics importance. However, most lncRNAs, except LINC01279 and LOC643733, indicated <3 target mRNAs and were not suitable for advanced bioinformatics analyses. Bioinformatics analyses demonstrated that there was a GO term for each lncRNA (proteinaceous extracellular for LINC01279 and cell surface for LOC643733). In conclusion, a set of coding RNA as well as lncRNAs differentially expressed in strabismus EOM samples were indicated. Notably, the present findings important information for advanced pathogenesis research and biomarkers detection.