Nuclear proteins and diabetic retinopathy: a review.

Diabetic retinopathy (DR) is an eye disease that causes blindness and vision loss in diabetic. Risk factors for DR include high blood glucose levels and some environmental factors. The pathogenesis is based on inflammation caused by interferon and other nuclear proteins. This review article provides an overview of DR and discusses the role of nuclear proteins in the pathogenesis of the disease. Some core proteins such as MAPK, transcription co-factors, transcription co-activators, and others are part of this review. In addition, some current advanced treatment resulting from the role of nuclear proteins will be analyzes, including epigenetic modifications, the use of methylation, acetylation, and histone modifications. Stem cell technology and the use of nanobiotechnology are proposed as promising approaches for a more effective treatment of DR.

A comparative study of 8-week complex training and resistance training on athletic performance of amateur futsal players.

Background: Despite the acknowledged importance of resistance training (RT) in enhancing physical performance in futsal players., the comparative effectiveness of RT and complex training (CT) on both physical and technical performance in futsal players remains underexplored. This study aimed to compare the effects of RT vs. CT on physical and technical performance in amateur futsal players. Method: Players from two amateur futsal teams were assigned to RT (one team of 16 players; 18 years) and CT (one team of 16 players; 18 years) to perform an 8-week intervention with two weekly sessions. The RT performed the squat and deadlift (6 sets of 6-10 repetitions at 75%-85% one-repetition maximum (1RM), while the CT performed the squat + squat jump and deadlift + high pull (3 sets of 4-6 + 10-12 repetitions at 75%-85% 1RM). Pre- and post-intervention assessments included the Futsal Special Performance Test (FSPT), repeated sprint ability (RSA), sprint decrement (Sdec), sprint times at 10-m (T10), 10-20-m (T10-20), and 20-m (T20), 1RM back squat (1RM BS), isometric mid-thigh pull (IMTP), and countermovement jump (CMJ). Results: At baseline, no significant differences between groups were observed for any variable analyzed (p > 0.05). After 8 weeks, there were significant differences between CT vs. RT on FSPT (-10.8% vs. -3.4%; p < 0.05), T10 (-5.2% vs. -0.1%; p < 0.05), IMTP (7.8% vs. 5.1%; p < 0.05), and CMJ (10.2% vs. 4.5%; p < 0.05). On the other hand, no significant differences between CT vs. RT were observed for RSA (-2.0% vs. -1.2%; p > 0.05), Sdec (-7.6% vs. -3.5%; p > 0.05), T10-20 (-0.9% vs. -0.9%; p > 0.05), T20 (-1.8% vs. -1.7%; p > 0.05), and 1RM BS (5.7% vs. 4.5%; p > 0.05) after the training program. Both groups significantly improved FSPT, T20, 1RM BS, and IMTP, while only CT significantly improved RSA, Sdec, T10, and CMJ. Conclusion: The results suggest that CT may be valuable for improving specific performance parameters in amateur futsal players, with some advantages over RT in enhancing strength and power. These findings support tailored training protocols for futsal players to optimize performance.

Incidence of chemotherapy-related cardiac dysfunction in cancer patients.

BACKGROUND: Cancer patients are increasingly affected by chemotherapy-related cardiac dysfunction. The reported incidence of this condition vary significantly across different studies. HYPOTHESIS: A better comprehensive understanding of chemotherapy-related cardiac dysfunction incidence in cancer patients is imperative. Therefore, we performed a meta-analysis to establish the overall incidence of chemotherapy-related cardiac dysfunction in cancer patients. METHODS: We searched articles in PubMed and EMBASE from database inception to May 1, 2023. Studies that reported the incidence of chemotherapy-related cardiac dysfunction in cancer patients were included. RESULTS: A total of 53 studies involving 35 651 individuals were finally included in the meta-analysis. The overall pooled incidence of chemotherapy-related cardiac dysfunction in cancer patients was 63.21 per 1000 person-years (95% CI: 57.28-69.14). The chemotherapy-related cardiac dysfunction incidence increased steeply within half a year of cancer chemotherapy. Also, the trend of chemotherapy-related cardiac dysfunction incidence appeared to have plateaued after a longer duration of follow-up. In addition, chemotherapy-related cardiac dysfunction incidence rates are significantly higher among patients with age ≥50 years versus patients with age <50 years (99.96 vs. 34.48 per 1000 person-years). The incidence rate of cardiac dysfunction was higher among breast cancer patients (72.97 per 1000 person-years), leukemia patients (65.21 per 1000 person-years), and lymphoma patients (55.43 per 1000 person-years). CONCLUSION: Our meta-analysis unveiled a definitive overall incidence rate of chemotherapy-related cardiac dysfunction in cancer patients. In addition, it was found that the risk of developing this condition escalates within the initial 6 months postchemotherapy, subsequently tapering off to become statistically insignificant after a duration of 6 years.

Deficiency of ASGR1 promotes liver injury by increasing GP73-mediated hepatic endoplasmic reticulum stress.

Liver injury is a core pathological process in the majority of liver diseases, yet the genetic factors predisposing individuals to its initiation and progression remain poorly understood. Here we show that asialoglycoprotein receptor 1 (ASGR1), a lectin specifically expressed in the liver, is downregulated in patients with liver fibrosis or cirrhosis and male mice with liver injury. ASGR1 deficiency exacerbates while its overexpression mitigates acetaminophen-induced acute and CCl4-induced chronic liver injuries in male mice. Mechanistically, ASGR1 binds to an endoplasmic reticulum stress mediator GP73 and facilitates its lysosomal degradation. ASGR1 depletion increases circulating GP73 levels and promotes the interaction between GP73 and BIP to activate endoplasmic reticulum stress, leading to liver injury. Neutralization of GP73 not only attenuates ASGR1 deficiency-induced liver injuries but also improves survival in mice received a lethal dose of acetaminophen. Collectively, these findings identify ASGR1 as a potential genetic determinant of susceptibility to liver injury and propose it as a therapeutic target for the treatment of liver injury.

Bis-Alkoxide Dysprosium(III) Crown Ether Complexes Exhibit Tunable Air Stability and Record Energy Barrier.

High-performance and air-stable single-molecule magnets (SMMs) can offer great convenience for the fabrication of information storage devices. However, the controversial requisition of high stability and magnetic axiality is hard to balance for lanthanide-based SMMs. Here, a family of dysprosium(III) crown ether complexes possessing hexagonal-bipyramidal (pseudo-D6h symmetry) local coordination geometry with tunable air stability and effective energy barrier for magnetization reversal (Ueff) are shown. The three complexes share the common formula of [Dy(18-C-6)L2][I3] (18-C-6 = 1,4,7,10,13,16-hexaoxacyclooctadecane; L = I, 1; L = OtBu 2 and L = 1-AdO 3). 1 is highly unstable in the air. 2 can survive in the air for a few minutes, while 3 remains unchanged in the air for more than 1 week. This is roughly in accordance with the percentage of buried volumes of the axial ligands. More strikingly, 2 and 3 show progressive enhancement of Ueff and 3 exhibits a record high Ueff of 2427(19) K, which significantly contributes to the 100 s blocking temperature up to 11 K for Yttrium-diluted sample, setting a new benchmark for solid-state air-stable SMMs.

Gelatin/carboxymethyl chitosan/aloe juice hydrogels with skin-like endurance and quick recovery: Preparation, characterization, and properties.

Gelatin-based hydrogels have gained considerable attention due to their resemblance to the extracellular matrix and hydrophilic three-dimensional network structure. Apart from providing an air-permeable and moist environment, these hydrogels optimize the inflammatory microenvironment of the wounds. These properties make gelatin-based hydrogels highly competitive in the field of wound dressings. In this study, a series of composite hydrogels were prepared using gelatin (Gel) and carboxymethyl chitosan (CMCh) as primary materials, glutaraldehyde as a crosslinker, and aloe vera juice as an anti-inflammatory component. The properties of the hydrogel, including its rheological properties, microscopic structures, mechanical properties, swelling ratios, thermal stability, antibacterial properties, and biocompatibility, were investigated. The results demonstrate that the gelatin-based hydrogels exhibit good elasticity and rapid self-healing ability. The hydrogels exhibited slight shear behavior, which is advantageous for skin care applications. Furthermore, the inclusion of aloe vera juice into the hydrogel resulted in a dense structure, improved mechanical properties and enhanced swelling ratio. The Gel/CMCh/Aloe hydrogels tolerate a compressive strength similar to that of human skin. Moreover, the hydrogels displayed excellent cytocompatibility with HFF-1 cells, and exhibited antibacterial activity against E. coli and S. aureus. Lomefloxacin was used as a model drug to study the releasing behavior of the Gel/CMCh/aloe hydrogels. The results showed that the drug was released rapidly at the initial stage, and could continue to be released for 12 h, the maximum releasing rate exceeded 20 %. These findings suggest that the gelatin-based hydrogels hold great promise as effective wound dressings.

Plasma Fibronectin as a Novel Predictor of Coronary Heart Disease: A Retrospective Study.

Although fibronectin has been associated with the pathogenesis of atherosclerosis, little is currently known about the relationship between plasma fibronectin and coronary heart disease (CHD). This retrospective study aimed to determine the predictive value of plasma fibronectin for CHD and its severity. A total of 1644 consecutive patients who underwent selective coronary angiography were recruited into the present study. The characteristics and results of the clinical examination of all patients were collected. Logistic regression analyses were performed to determine the predictive value of plasma fibronectin for the presence and severity of CHD. Compared with non-CHD patients, the CHD patients showed significantly higher plasma levels of troponin I and creatine kinase isoenzyme, along with lower plasma levels of fibronectin. However, no significant differences were detected in plasma fibronectin among patients with different grades of CHD. The logistic regression model showed that plasma fibronectin remained an independent predictor of CHD after adjustment with a 1.39-fold increased risk for every 1 SD decrease in plasma fibronectin. Nevertheless, plasma fibronectin could not predict the severity of CHD determined by the number of stenosed vessels and the modified Gensini score. This study demonstrated that lower plasma fibronectin might be an independent predictor of CHD, but it may be of no value in predicting the severity of CHD.

Alternative splicing of CEACAM1 by hypoxia-inducible factor-1α enhances tolerance to hepatic ischemia in mice and humans.

Although alternative splicing (AS) drives transcriptional responses and cellular adaptation to environmental stresses, its contributions in organ transplantation have not been appreciated. We have shown that carcinoembryonic antigen-related cell adhesion molecule (Ceacam1; CD66a), a transmembrane biliary glycoprotein expressed in epithelial, endothelial, and immune cells, determines donor liver transplant quality. Here, we studied how AS of Ceacam1 affects ischemia-reperfusion injury (IRI) in mouse and human livers. We found that the short cytoplasmic isoform Ceacam1-S increased during early acute and late resolution phases of warm IRI injury in mice. Transfection of Ceacam1-deficient mouse hepatocytes with adenoviral Ceacam1-S mitigated hypoxia-induced loss of cellular adhesion by repressing the Ask1/p-p38 cell death pathway. Nucleic acid-blocking morpholinos, designed to selectively induce Ceacam1-S, protected hepatocyte cultures against temperature-induced stress in vitro. Luciferase and chromatin immunoprecipitation assays identified direct binding of hypoxia-inducible factor-1α (Hif-1α) to the mouse polypyrimidine tract binding protein 1 (Ptbp1) promoter region. Dimethyloxalylglycine protected mouse livers from warm IR stress and hepatocellular damage by inhibiting prolyl hydroxylase domain-containing protein 1 and promoting AS of Ceacam1-S. Last, analysis of 46 human donor liver grafts revealed that CEACAM1-S positively correlated with pretransplant HIF1A expression. This also correlated with better transplant outcomes, including reduced TIMP1, total bilirubin, proinflammatory MCP1, CXCL10 cytokines, immune activation markers IL17A, and incidence of delayed complications from biliary anastomosis. This translational study identified mouse Hif-1α-controlled AS of Ceacam1, through transcriptional regulation of Ptbp1 promoter region, as a functional underpinning of hepatoprotection against IR stress and tissue damage in liver transplantation.

The role of glucocorticoids in increasing cardiovascular risk.

Introduction: Different studies provide conflicting evidence regarding the potential for glucocorticoids (GCs) to increase the risk of cardiovascular diseases. This study performed a systematic review and meta-analysis to determine the correlation between GCs and cardiovascular risk, including major adverse cardiovascular events (MACE), death from any cause, coronary heart disease (CHD), heart failure (HF), and stroke. Methods: We performed a comprehensive search in PubMed and Embase (from inception to June 1, 2022). Studies that reported relative risk (RR) estimates with 95% confidence intervals (CIs) for the associations of interest were included. Results: A total of 43 studies with 15,572,512 subjects were included. Patients taking GCs had a higher risk of MACE (RR = 1.27, 95% CI: 1.15-1.40), CHD (RR = 1.25, 95% CI: 1.11-1.41), and HF (RR = 1.92, 95% CI: 1.51-2.45). The MACE risk increased by 10% (95% CI: 6%-15%) for each additional gram of GCs cumulative dose or by 63% (95% CI: 46%-83%) for an additional 10 µg daily dose. The subgroup analysis suggested that not inhaled GCs and current GCs use were associated with increasing MACE risk. Similarly, GCs were linked to an increase in absolute MACE risk of 13.94 (95% CI: 10.29-17.58) cases per 1,000 person-years. Conclusions: Administration of GCs is possibly related with increased risk for MACE, CHD, and HF but not increased all-cause death or stroke. Furthermore, it seems that the risk of MACE increased with increasing cumulative or daily dose of GCs.