Irigenin Alleviates Blue Light-Induced Retinal Damage by Upregulating Antioxidative Defense System via Nrf2 Pathway In Vivo and In Vitro.

This research aimed to assess the potential of irigenin to attenuate blue light (BL)-induced apoptosis in human adult retinal pigment epithelial (hARPE-19) cells loaded with N-retinylidene-N-retinylethanolamine (A2E, DA50062). Furthermore, the study investigated the associated molecular mechanisms. Cell viability was assessed using the MTT assay, and flow cytometry was employed to evaluate reactive oxygen species (ROS) production, alterations in mitochondrial membrane potential, and cytochrome c release.

Transfer Learning Prediction of Early Exposures and Genetic Risk Score on Adult Obesity in Two Minority Cohorts.

Due to ethnic heterogeneity in genetic architecture, genetic risk score (GRS) constructed within the European population generally possesses poor portability in underrepresented non-European populations, but substantial genetic similarity exists across diverse ancestral groups. We here explore the prediction performance of early exposures and GRS on body mass index (BMI) through leveraging genetic similarity knowledge acquired from Europeans into non-Europeans. We present a linear mixed prediction model for BMI in three distinct UK Biobank cohorts under the transfer learning framework, where we consider Asians (n = 7487) and Africans (n = 7533) as target samples and Europeans (n = 280,575) as informative auxiliary samples.

Polygenic prediction for underrepresented populations through transfer learning by utilizing genetic similarity shared with European populations.

Because current genome-wide association studies are primarily conducted in individuals of European ancestry and information disparities exist among different populations, the polygenic score derived from Europeans thus exhibits poor transferability. Borrowing the idea of transfer learning, which enables the utilization of knowledge acquired from auxiliary samples to enhance learning capability in target samples, we propose transPGS, a novel polygenic score method, for genetic prediction in underrepresented populations by leveraging genetic similarity shared between the European and non-European populations while explaining the trans-ethnic difference in linkage disequilibrium (LD) and effect sizes. We demonstrate the usefulness and robustness of transPGS in elevated prediction accuracy via individual-level and summary-level simulations and apply it to seven continuous phenotypes and three diseases in the African, Chinese, and East Asian populations of the UK Biobank and Genetic Epidemiology Research Study on Adult Health and Aging cohorts.

Comparison of population pharmacokinetic modeling and machine learning approaches for predicting voriconazole trough concentrations in critically ill patients.

Background: Despite the widespread use of voriconazole in antifungal treatment, its high pharmacokinetic and pharmacodynamic variability may lead to suboptimal efficacy, especially in intensive care unit (ICU) patients. Machine learning (ML), an artificial intelligence modeling approach, is increasingly being applied to personalized medicine. The effectiveness of ML models for predicting voriconazole blood concentrations in ICU patients, compared to traditional population pharmacokinetics (popPK) models, has been uncertain until now.

Discussion on the treatment of diabetic kidney disease based on the "gut-fat-kidney" axis.

Diabetic kidney disease is the main cause of end-stage renal disease, and its prevention and treatment are still a major clinical problem. The human intestine has a complex flora of hundreds of millions of microorganisms, and intestinal microorganisms, and their derivatives are closely related to renal inflammatory response, immune response, and material metabolism. Brown adipose tissue is the main part of adaptive thermogenesis.

Breastfeeding, genetic susceptibility, and the risk of asthma and allergic diseases in children and adolescents: a retrospective national population-based cohort study.

Background: Asthma and allergic diseases (such as allergic rhinitis) are multifactorial chronic respiratory diseases, and have many common pathogenic mechanisms. This study aimed to assess the joint effects of breastfeeding and genetic susceptibility on asthma, allergic disease in children and adolescents and sought to examine whether the effect of breastfeeding was consistent under distinct levels of genetic risk.

Methods: A total of 351,931 UK Biobank participants were analyzed.

Enhancing ocular protection against UVB: The role of irigenin in modulating oxidative stress and apoptotic pathways In Vivo.

Oxidative damage contributes to age-related macular degeneration. Irigenin possesses diverse pharmacologic properties, including antioxidative and antiapoptotic effects. Our in vivo experiments indicated that irigenin mitigates UVB-induced histopathologic changes and oxidative DNA damage.

Clinical comparative study of laparoscopic partial splenectomy and open partial splenectomy.

Introduction: The aim of the article was too investigate and compare the feasibility, safety, and early postoperative recovery associated with laparoscopic partial splenectomy (LPS) and open partial splenectomy (OPS) in patients with benign splenic tumours and traumatic splenic rupture.

Material And Methods: A retrospective analysis was conducted on clinical data from 110 patients undergoing splenic resection at our hospital between March 2019 and May 2022. Among them, 35 patients underwent OPS, 25 underwent LPS for traumatic splenic rupture, while 50 patients with benign splenic tumours underwent either OPS (n = 20) or LPS (n = 30).

Cryoablation combined with dual immune checkpoint blockade enhances antitumor efficacy in hepatocellular carcinoma model mice.

Background: Cryoablation (Cryo) is a minimally invasive treatment for tumors. Cryo can activate the body's immune response, although it is typically weak. The immune response induced by Cryo in hepatocellular carcinoma (HCC) is poorly understood.

tRNA-derived RNA fragment, tRF-18-8R6546D2, promotes pancreatic adenocarcinoma progression by directly targeting ASCL2.

Pancreatic adenocarcinoma (PAAD) is a life-threatening cancer. Exploring new diagnosis and treatment targets helps improve its prognosis. tRNA-derived small non-coding RNAs (tsRNAs) are a novel type of gene expression regulators and their dysregulation is closely related to many human cancers.

Central role of Sigma-1 receptor in ochratoxin A-induced ferroptosis.

Ochratoxin A (OTA), a secondary fungal metabolite known for its nephrotoxic effects, is prevalent in various feeds and food items. Our recent study suggests that OTA-induced nephrotoxicity is linked to the Sigma-1 receptor (Sig-1R)-mediated mitochondrial pathway apoptosis in human proximal tubule epithelial-originated kidney-2 (HK-2) cells. However, the contribution of Sig-1R to OTA-induced nephrotoxicity involving other forms of regulated cell death, such as ferroptosis, remains unexplored.

Pregnane X receptor activation induces liver enlargement and regeneration and simultaneously promotes the metabolic activity of CYP3A1/2 and CYP2C6/11 in rats.

Human pregnane X receptor (PXR) is critical for regulating the expression of key drug-metabolizing enzymes such as CYP3A and CYP2C. Our recent study revealed that treatment with rodent-specific PXR agonist pregnenolone-16α-carbonitrile (PCN) significantly induced hepatomegaly and promoted liver regeneration after two-thirds partial hepatectomy (PHx) in mice. However, it remains unclear whether PXR activation induces hepatomegaly and liver regeneration and simultaneously promotes metabolic function of the liver.

Hsa_circ_0007590/PTBP1 complex reprograms glucose metabolism by reducing the stability of mA-modified PTEN mRNA in pancreatic ductal adenocarcinoma.

The role of circular RNAs (circRNAs) in glucose metabolism in pancreatic duct adenocarcinoma (PDAC) remains elusive. Through RNA sequencing of cells cultured under conditions of glucose deprivation, we identified hsa_circ_0007590. Sanger sequencing and RNase R and Act D treatments were performed to confirm the circular RNA features of hsa_circ_0007590.

Treatment of landfill leachate by black soldier fly (Hermetia illucens L.) larvae and the changes of intestinal microbial community.

Black soldier fly larvae (BSFL) (Hermetia illucens) are commonly used to treat organic waste. This work aims to evaluate the transformation effect, heavy metal migration, and alterations in the gut microbiota of BSFL in addition to treating landfill leachate (LL) with BSFL. We found that BSFL may grow in various landfill leachate concentrations without obvious toxicity and growth inhibition.

Chlorpyrifos-induced suppression of the antioxidative defense system leads to cytotoxicity and genotoxicity in macrophages.

Chlorpyrifos, widely used for pest control, is known to have various harmful effects, although its toxic effects in macrophages and the mechanisms underlying its toxicity remain unclear. The present study investigated the toxic effects of chlorypyrifos in a macrophage cell line. Here, we found that chlorpyrifos induced cytotoxicity and genotoxicity in RAW264.

Vascular endothelial dysfunction induced by 3-bromofluoranthene via MAPK-mediated-NFκB pro-inflammatory pathway and intracellular ROS generation.

3-Bromofluoranthene (3-BrFlu) is the secondary metabolite of fluoranthene, which is classified as a polycyclic aromatic hydrocarbon, through bromination and exists in the fine particulate matter of air pollutants. Endothelial dysfunction plays a critical role in the pathogenesis of cardiovascular and vascular diseases. Little is known about the molecular mechanism of 3-BrFlu on endothelial dysfunction in vivo and in vitro assay.

Teaghrelin protected dopaminergic neurons in MPTP-induced Parkinson's disease animal model by promoting PINK1/Parkin-mediated mitophagy and AMPK/SIRT1/PGC1-α-mediated mitochondrial biogenesis.

Mitochondrial dysfunction, a common cellular hallmark in both familial and sporadic forms of Parkinson's disease (PD), is assumed to play a significant role in pathologic development and progression of the disease. Teaghrelin, a unique bioactive compound in some oolong tea varieties, has been demonstrated to protect SH-SY5Y cells against 1-methyl-4-phenylpyridinium induced neurotoxicity by binding to the ghrelin receptor to activate the AMPK/SIRT1/PGC-1α pathway. In this study, an animal model was established using a neurotoxin, 1-methyl-4phenyl-1,2,3,6-tetrahydropyridine (MPTP), a byproduct of a prohibited drug, to evaluate the oral efficacy of teaghrelin on PD by monitoring motor dysfunction of mice in open field, pole, and bean walking tests.

3D MR elastography-based stiffness as a marker for predicting tumor grade and subtype in cervical cancer.

Background: Increasing evidence has indicated that high tissue stiffness (TS) may be a potential biomarker for evaluation of tumor aggressiveness.

Purpose: To investigate the value of magnetic resonance elastography (MRE)-based quantitative parameters preoperatively predicting the tumor grade and subtype of cervical cancer (CC).

Study Type: Retrospective.

Cyclizine induces cytotoxicity and apoptosis in macrophages through the extrinsic and intrinsic apoptotic pathways.

Cyclizine, an over-the-counter and prescription antihistamine, finds widespread application in the prevention and treatment of motion sickness, encompassing symptoms such as nausea, vomiting, dizziness, along with its effectiveness in managing vertigo. However, the overuse or misuse of cyclizine may lead to hallucinations, confusion, tachycardia, and hypertension. The molecular mechanisms underlying cyclizine-induced cytotoxicity and apoptosis remain unclear.

Wogonin induces apoptosis in macrophages by exhibiting cytotoxic and genotoxic effects.

Macrophages play an important role in defending the body against invading pathogens. In the face of pathogens, macrophages become activated and release toxic materials that disrupt the pathogens. Macrophage overactivation can lead to severe illness and inflammation.