Journal: Aging Cell

Article Title: Aerobic Exercise Attenuates Autophagy‐Lysosomal Flux Deficits via β2‐AR‐Mediated ESCRT‐III Subunit CHMP4B in Mice With Human MAPT P301L

doi: 10.1111/acel.70184

Figure Lengend Snippet: AE upregulates CHMP4B expression through β2‐AR‐RXRα signaling in MAPT P301L mice. (A and B) The mRNA and protein levels of β2‐AR in the hippocampus of WT, MAPT and AE‐treated MAPT mice ( n = 6 mice per group). (C and D) The level of HT7, β2‐AR, pSβ2‐AR, SQSTM1 and LC3‐II in N2a cells with overexpression of MAPT and treated with Teb ( n = 6 independent experiments for each group). (E) Representative images of autophagic flux and (F) quantification of LC3 puncta in N2a cells with overexpression of MAPT and treated with Teb (8 images from n = 4 independent experiments for each group). (G and H) The protein levels of HT7, CHMP4B, SQSTM1 and LC3‐II in the N2a cells with overexpression of MAPT and CHMP4B and treated with si Adrb 2 and si Chmp4b or Teb detected by western blotting ( n = 6 independent experiments for each group). (I‐L) The mRNA levels of the Chmp4b transcription factors Thap11 , Nr2f6 , Prdm15 and Rxrα in the hippocampus of WT, MAPT and MAPT+AE mice ( n = 6 mice per group). (M and N) The protein levels of RXRα in the hippocampus of WT, MAPT and MAPT+AE mice ( n = 6 mice per group). (O) Schematic diagram revealing the mouse CHMP4B promoter region and Rxrα potential binding Site1 and Site2. (P) ChIP assay results determined the enrichment of RXRα at potential binding site 1 and site 2 of the CHMP4B promoter region. (Q) The direct binding capacity of RXRα at Site2 to the CHMP4B promoter was validated using qPCR of the ChIP products ( n = 6 mice per group). (R) Diagram of the principle of Dual‐luciferase experiment. (S) Dual‐luciferase reporter gene assays the binding level of RXRα to the CHMP4B promoter at Site2 in N2a cells with overexpression of RXRα and treated with si Rxrα ( n = 6 independent experiments for each group). (T and U) The protein levels of CHMP4B in the N2a cells with overexpression of MAPT and treated with si Rxrα or Teb were detected by western blotting ( n = 6 mice per group). * p < 0.05; ** p < 0.01; *** p < 0.001; **** p < 0.0001. The data are presented as the means ± SEMs. One‐way ANOVA with Bonferroni post hoc test was used to analyze the data.

Article Snippet: Mice were treated with the systemic β2‐AR antagonist propranolol (MedChemExpress, HY‐B0573B) at a dose of 30 mg/kg by intragastric administration 1 h prior to the AE (Tsai et al. ).

Techniques: Expressing, Over Expression, Western Blot, Binding Assay, Luciferase

Journal: Aging Cell

Article Title: Aerobic Exercise Attenuates Autophagy‐Lysosomal Flux Deficits via β2‐AR‐Mediated ESCRT‐III Subunit CHMP4B in Mice With Human MAPT P301L

doi: 10.1111/acel.70184

Figure Lengend Snippet: The β2‐AR inhibitor propranolol reverses the ameliorative effects on cognition and pathology in MAPT P301L mice after AE. (A) Escape latency to the hidden platform during the 6‐day training trials in the MWM test ( n = 8 mice per group). * p < 0.05, (MAPT+AE vs. MAPT); # p < 0.05, ## p < 0.01 (MAPT+AE + Prop vs. MAPT+AE). (B) The swimming pathway traveled to locate the platform on day 7. (C) Escape latency, (D) number of crossings of the hidden platform area, (E) the time in target quadrants and (F) swimming speed on day 7. (G and H) The protein levels of SQSTM1 and LC3‐II in the hippocampus of the AE and propranolol‐inhibited groups ( n = 6 mice per group). (I and J) Electron microscopy analysis of autophagosomes shows arrows indicating autophagosomes ( n = 9 images from 3 mice per group; scale bar: 0.5 μm). (K and L) The protein levels of soluble Tau of (pS396, pS404, pT231 and Tau5) in the hippocampus were detected using western blotting and quantitatively analyzed. (M) Representative confocal images of LC3 and Tau5 immunofluorescence co‐labeling in the DG region of the hippocampus of the mice. (N) Quantification of the ratio of LC3 + Tau5 + :Tau5 + . (O and P) Nissl staining and quantification of intact neurons in the hippocampal CA1 region of mice. ( n = 6 mice per group). (Q and R) The protein levels of RXRα and CHMP4B in the hippocampus of the AE and propranolol‐inhibited groups ( n = 6 mice per group). * p < 0.05; ** p < 0.01; *** p < 0.001; **** p < 0.0001. The data are presented as the means ± SEMs. Two‐way ANOVA with Bonferroni post hoc test was used for (A), and one‐way ANOVA with Bonferroni post hoc test was used to analyze the data in (C–F) and unpaired t ‐test for the other data.

Article Snippet: Mice were treated with the systemic β2‐AR antagonist propranolol (MedChemExpress, HY‐B0573B) at a dose of 30 mg/kg by intragastric administration 1 h prior to the AE (Tsai et al. ).

Techniques: Electron Microscopy, Western Blot, Immunofluorescence, Labeling, Staining

Journal: Polymers

Article Title: Development of a 3D Printed Coating Shell to Control the Drug Release of Encapsulated Immediate-Release Tablets

doi: 10.3390/polym12061395

Figure Lengend Snippet: Illustration representing encapsulation of the propranolol HCl tablet soaked with color dye (methylene blue) kept inside 3D printed controlled-release shell, with the gradual increase in the intensity of the color solution showing the visual observation of methylene blue release through the 3D printed controlled-release shell at different time intervals.

Article Snippet: An assay of the propranolol HCl tablet was performed as per the method described in the British Pharmacopoeia to determine the drug content.

Techniques: Encapsulation

Journal: Polymers

Article Title: Development of a 3D Printed Coating Shell to Control the Drug Release of Encapsulated Immediate-Release Tablets

doi: 10.3390/polym12061395

Figure Lengend Snippet: ( a ) Cumulative release of propranolol HCl from the model tablet with phosphate buffer (pH 6.8) as dissolution media at temperature 37 ± 0.5 °C versus when enclosed inside 3D printed coating shells with different excipient ratios . ( b ) The coating shell system still intact after the dissolution experiment. The cross-section of the shell shows the expansion of the propranolol HCl tablet inside the shell.

Article Snippet: An assay of the propranolol HCl tablet was performed as per the method described in the British Pharmacopoeia to determine the drug content.

Techniques: Dissolution

Journal: Polymers

Article Title: Development of a 3D Printed Coating Shell to Control the Drug Release of Encapsulated Immediate-Release Tablets

doi: 10.3390/polym12061395

Figure Lengend Snippet: ( a ) Different sizes of 3D printed controlled-release shells illustrating the gap/space between the enclosed tablet and the shell wall. ( b ) Cumulative release of propranolol HCl with phosphate buffer (pH 6.8) as dissolution media at temperature 37 ± 0.5 °C from 3D printed controlled-release shells of different sizes.

Article Snippet: An assay of the propranolol HCl tablet was performed as per the method described in the British Pharmacopoeia to determine the drug content.

Techniques: Dissolution

Journal: Polymers

Article Title: Development of a 3D Printed Coating Shell to Control the Drug Release of Encapsulated Immediate-Release Tablets

doi: 10.3390/polym12061395

Figure Lengend Snippet: In vitro release kinetics of propranolol HCl from 3D printed controlled-release shells of variable composition and size fitted to the best-fit release kinetic model.

Article Snippet: An assay of the propranolol HCl tablet was performed as per the method described in the British Pharmacopoeia to determine the drug content.

Techniques: In Vitro, Formulation

Journal: Investigative Ophthalmology & Visual Science

Article Title: Chronic Restraint Stress Misaligns Corneal Clock via β-Adrenergic and Glucocorticoid Signaling, Altering Epithelial, Neural, Immune, Metabolic States

doi: 10.1167/iovs.66.15.50

Figure Lengend Snippet: RS misaligns the corneal clock and perturbs ocular-surface homeostasis via sympathetic and HPA-axis activation. Schematic of the working model. RS activates the SNS and the HPA axis, increasing circulating catecholamines (EPI/NE) and glucocorticoids (corticosterone). These neuroendocrine signals impinge on the cornea to disrupt circadian timing (phase advance/amplitude dampening) and triggering functional changes across multiple domains: immune suppression (fewer neutrophils and γδ-T cells), metabolic/antioxidant upregulation (ATP and glutathione pathways), epithelial hyperproliferation (basal mitoses), barrier weakening (ZO-1/occludin↓), and enhanced corneal mechanical sensitivity. Pharmacologic modulation—β-adrenergic receptor blockade (e.g., propranolol) and inhibition of glucocorticoid synthesis (e.g., metyrapone)—partially attenuates clock misalignment and functional abnormalities, indicating distinct yet complementary roles of SNS and HPA signaling in stress-induced corneal reprogramming.

Article Snippet: The RS + Pro group received propranolol (cat# S4076; Selleck Chemicals, Houston, TX, USA) administered ad libitum in drinking water at a concentration of 0.5 g/L, consistent with previously validated regimens.

Techniques: Activation Assay, Functional Assay, Inhibition

Journal: International Journal of Molecular Sciences

Article Title: R-Propranolol Has Broad-Spectrum Anti-Coronavirus Activity and Suppresses Factors Involved in Pathogenic Angiogenesis

doi: 10.3390/ijms24054588

Figure Lengend Snippet: Effect of R-propranolol and S-propranolol on SARS-CoV-2-induced cytopathic effect in Vero E6 cells. CPE reduction assays were carried out on Vero E6 cells infected with SARS-CoV-2 (MOI of 0.015). Cells were pretreated with and infected in the presence of ( a ) R-propranolol, or ( b ) S-propranolol. At 72 hpi, cell viability was determined by MTS assay. n = 2 independent experiments. Cell viability of uninfected compound-treated cells was measured in parallel to assess the cytotoxicity of the compound. Mean ± SEM is shown. The 50% inhibitory concentration (IC50) was determined by non-linear regression with GraphPad Prism 6.

Article Snippet: R-(+)-Propranolol hydrochloride, S-(+)-Propranolol hydrochloride, and phorbol-12-myristate-13-acetate (PMA) were purchased from MedChemExpress and dissolved in DMSO.

Techniques: Infection, MTS Assay, Concentration Assay