LRP6 Knockdown Ameliorates Insulin Resistance via Modulation of Autophagy by Regulating GSK3β Signaling in Human LO2 Hepatocytes

Recent studies suggest that autophagy is highly involved in insulin resistance (IR). Inhibition of the PI3K/AKT/mTOR signaling pathway induces autophagy activation. Additionally, depletion of LRP6 has been shown to increase insulin sensitivity but its mechanism is still not clear. We hypothesized that LRP6 contributes to IR by regulating mTOR mediated autophagy through GSK3β in hepatocytes. LO2 hepatocytes were treated with palmitate (PA) and insulin to induced IR. Levels of LRP6 mRNA and protein expression were measured by real time-PCR and western blot analysis. LRP6 knock down was achieved by adenovirus mediated Si-LRP6 expression and its roles in IR, glucose, GSK3β, mTOR signaling, and autophagy were explored. Finally, GSK3β was overexpressed and its involvement in autophagy and IR was examined. We found that PA treatment led to a reduced glucose uptake and IR in hepatocytes, which was accompanied by an upregulation of LRP6 expression. Knocking down of LRP6 enhanced glucose uptake and insulin sensitivity in PA treated cells, probably through increasing GSK3b activity. Overexpression of GSK3b mimicked LRP6 reduction by enhancing autophagy and ameliorating IR. Our study revealed a significant molecular mechanism connecting LRP6 to insulin sensitivity through GSK3β-mTOR mediated autophagy

A multicentre study on the clinical characteristics of newborns infected with coronavirus disease 2019 during the omicron wave

ObjectiveTo investigate the clinical characteristics and outcomes of newborns infected with coronavirus disease 2019 (COVID-19) during the Omicron wave.MethodsFrom December 1, 2022, to January 4, 2023, clinical data were collected from neonates with COVID-19 who were admitted to 10 hospitals in Foshan City, China. Their epidemiological histories, clinical manifestations and outcomes were analysed. The neonates were divided into symptomatic and asymptomatic groups. The t test or χ2 test was used for comparisons between groups.ResultsA total of 286 children were diagnosed, including 166 males, 120 females, 273 full-term infants and 13 premature infants. They were 5.5 (0–30) days old on average when they were admitted to the hospital. These children had contact with patients who tested positive for COVID-19 and were infected through horizontal transmission. This study included 33 asymptomatic and 253 symptomatic patients, among whom 143 were diagnosed with upper respiratory tract infections and 110 were diagnosed with pneumonia. There were no severe or critical patients. Fever (220 patients) was the most common clinical manifestation, with a duration of 1.1 (1–6) days. The next most common clinical manifestations were cough with nasal congestion or runny nose (4 patients), cough (34 patients), poor appetite (7 patients), shortness of breath (15 patients), and poor general status (1 patient). There were no significant abnormalities in routine blood tests among the neonates infected with COVID-19 except for mononucleosis. However, compared with the asymptomatic group, in the symptomatic group, the leukocyte and neutrophil granulocyte counts were significantly decreased, and the monocyte count was significantly increased. C-reactive protein (CRP) levels were significantly increased (≥10 mg/L) in 9 patients. Myocardial enzyme, liver function, kidney function and other tests showed no obvious abnormalities.ConclusionsIn this study, neonates infected with the Omicron variant were asymptomatic or had mild disease. Symptomatic patients had lower leucocyte and neutrophil levels than asymptomatic patients

Identification of Tumor‐Specific Surface Proteins Enables Quantification of Extracellular Vesicle Subtypes for Early Detection of Pancreatic Ductal Adenocarcinoma

Pancreatic ductal adenocarcinoma (PDAC) is a leading cause of cancer-related mortality, largely due to late-stage diagnosis. Reliable early detection methods are critically needed. PDAC-derived extracellular vesicles (EVs) carry molecules that reflect their parental tumor cells and are detectable in early disease stages, offering a promising noninvasive diagnostic approach. Here, a streamlined PDAC EV Surface Protein Assay for quantifying PDAC EV subpopulations in 300-µL plasma through a two-step workflow is presented: i) click chemistry-mediated EV enrichment using EV Click Beads and trans-cyclooctene-grafted antibodies targeting three PDAC EV-specific surface proteins (MUC1, EGFR, and TROP2), and ii) quantification of enriched PDAC EVs through reverse transcription-quantitative polymerase chain reaction. The three PDAC EV-specific surface proteins are identified using a bioinformatics framework and validated on PDAC cell lines and tissue microarrays. The resultant PDAC EV Score, derived from signals of the three PDAC EV subpopulations, demonstrates robust differentiation of PDAC patients from noncancer controls, with area under the receiver operating characteristic curves of 0.94 in the training (n = 124) and 0.93 in the validation (n = 136) cohorts. This EV-based diagnostic approach successfully exploits PDAC EV subpopulations as novel biomarkers for PDAC early detection, translating PDAC surface proteins into an EV-based liquid biopsy platform

Histidine functionalized MIL-53(Al) for lead(<scp>ii</scp>) removal from aqueous solution

Introduction of histidine as a new modified material in MIL-53(Al) to enhance the adsorption properties for Pb(ii).</jats:p

Exosomes derived from BMSCs regulate pyroptosis by miR-143-3p/MyD88 axis to ameliorate intestinal ischemia-reperfusion injury

Abstract Intestinal ischemia-reperfusion (I/R) injury is a condition in which tissue injury is aggravated after ischemia due to recovery of blood supply. Bone marrow mesenchymal stem cell-derived exosome (BMSC-exo) showed a positive effect on I/R injury. This study aimed to investigate the effects and possible mechanism of BMSC-exo on intestinal I/R injury based on pyroptosis. BMSC-exos were isolated by super-centrifugation methods. Cell proliferation and apoptosis in the cell model, and intestinal barrier injury in the mouse model were analyzed to explore the effects of BMSC-exo on intestinal I/R, and inflammatory cytokines and pyroptosis-related proteins were analyzed to explore the effects of BMSC-exo on pyroptosis. In addition, miRNA microarray sequencing was used to analyze the differentially expressed miRNA in the regulation of BMSC-exo in intestinal I/R to further elucidate the mechanism. The results showed that BMSC-exo effectively reduced cell apoptosis, alleviated intestinal barrier injury, and regulated the expression of inflammatory cytokines and pyroptosis-related protein, suggesting that BMSC-exo may alleviate intestinal I/R injury by regulating pyroptosis in vitro and in vivo. In addition, the differentially expressed miRNA screened by miRNA microarray sequencing was miR-143-3p. Bioinformatics analysis predicted that there was a binding site between miR-143-3p and MyD88, and dual-luciferase reporter assay confirmed that miR-143-3p could directly target MyD88 and regulate its expression. Further studies verified that miR-143-3p may regulate pyroptosis by regulating NLRP3 through the TLR4/MyD88/NF-кB pathway and participate in BMSC-exo to alleviat intestinal I/R. In conclusion, this study found that BMSC-exo alleviated intestinal I/R by regulating pyroptosis through the miR-143-3p/MyD88/NF-кB/NLRP3 axis.</jats:p

Biomimetic Nanomaterials Triggered Ferroptosis for Cancer Theranostics

10.3389/fchem.2021.768248Frontiers in Chemistry976824

The identification of heterogeneous reactive oxygen subtypes in esophageal squamous cell carcinoma to aid patient prognosis and immunotherapy

Introduction: Esophageal cancer is increasingly recognized as a significant global malignancy. The main pathological subtype of this cancer is esophageal squamous cell carcinoma (ESCC), which displays a higher degree of malignancy and a poorer prognosis. Reactive oxygen species (ROS) play a critical role in modulating the immune response to tumors, and understanding the regulation of ROS in ESCC could lead to novel and improved therapeutic strategies for ESCC patients. Methods: A consensus matrix derived from genes involved in the ROS pathway revealed two subtypes of ROS. These subtypes were categorized as ROS-active or ROS-suppressive based on their level of ROS activity. The heterogeneity among the different ROS subtypes was then explored from various perspectives, including gene function, immune response, genomic stability, and immunotherapy. In order to assess the prognosis and the potential benefits of immunotherapy, a ROS activity score (RAS) was developed using the identified ROS subtypes. In vitro experiments were performed to confirm the impact of core RAS genes on the proliferative activity of esophageal cancer cell lines. Results: Two distinctive subtypes of ROS were identified. The first subtype, referred to as ROS-active, exhibited elevated ROS activity, enhanced involvement in cancer-associated immune pathways, and increased infiltration of effector immune cells. The second subtype, named ROS-suppressive, demonstrated weaker ROS activity but displayed more pronounced dysregulation in the cell cycle and a denser extracellular matrix, indicating malignant characteristics. Genomic stability, particularly in terms of copy number variation (CNV) events, differed between the two ROS subtypes. By developing a RAS model, reliable risk assessment for overall survival (OS) in patients with ESCC was achieved, and the model demonstrated strong predictive capabilities in real-world immunotherapy cohorts. Moreover, the core gene LDLRAD1 within the RAS model was found to enhance proliferative activity in esophageal cancer cell lines. Conclusion: Based on the ROS pathway, we successfully identified two distinct subtypes in ESCC: the ROS-active subtype and the ROS-suppressive subtype. These subtypes were utilized to evaluate prognosis and the sensitivity to immunotherapy