Journal: Aging Cell

Article Title: Down‐Regulation of TFEB With Defective Autophagy in the Susceptibility of Aging Kidneys to Septic Acute Kidney Injury

doi: 10.1111/acel.70644

Figure Lengend Snippet: Modulation of autophagy in senescent BUMPT cells bidirectionally regulates their susceptibility to LPS‐induced injury. (A–F) Treatment of LPS‐treated senescent BUMPT cells with Tat‐Beclin 1 peptide (30 μM) and chloroquine (20 μM), respectively. (A) Representative immunoblots of LC3‐I/II, c‐CAS3 and GAPDH expression of BUMPT cells treated with Tat‐Beclin 1 peptide, and (B) corresponding densitometric quantification. (C) Representative immunoblots of LC3‐I/II, c‐CAS3 and GAPDH expression of BUMPT cells treated with chloroquine and (D) corresponding densitometric quantification. (E) Representative images of TUNEL assay (red). Hochest was used to stain the nucleus (blue); scale bar = 50 μm. (F) Relative mRNA expression levels of the genes encoding Il‐6, Mcp‐1 and Tnfα , assessed by RT‐qPCR. All quantitative data are expressed as mean ± SEM. * p < 0.05.

Article Snippet: For LPS treatment, cells were incubated with DMEM medium containing 0.2% FBS and 10 μg/mL LPS for 24 h. For Tat‐Beclin 1 peptide (HY‐P2260, Medchemexpress) treatment, cells were incubated with DMEM medium containing 0.2% FBS and 30 μM Tat‐Beclin 1 peptide for 8 h. For chloroquine (C6628, Sigma‐aldrich) treatment, cells were incubated with DMEM medium containing 0.2% FBS and 20 μM for an additional 8 h. For detection of autophagic flux in cells, normal BUMPT cells and senescence‐induced BUMPT cells were transiently transfected with mRFP‐GFP‐LC3 (ptfLC3, 21,074, Addgene).

Techniques: Western Blot, Expressing, TUNEL Assay, Staining, Quantitative RT-PCR

Journal: Neoplasia (New York, N.Y.)

Article Title: PIK3CA mutant cervical cancer is selectively suppressed by PI3Kα inhibition (Alpelisib/BYL-719 and Inavolisib/GDC-0077) and cooperates with HPV directed T cell therapy

doi: 10.1016/j.neo.2026.101305

Figure Lengend Snippet: Modular structures of the two most prevalent oncoproteins, p110 ( PIK3CA) and YAP1, in CC development. (A) Somatic mutations in the helical domain of PIK3CA, activating the p110 catalytic subunit of PIK3CA, and YAP1 amplification occur frequently in CC. (B) PIK3CA mutations and YAP1 amplification are significantly mutually exclusive. The numbers represent the combined data from TCGA-CESC, MSKCC, and AACR-GENIE datasets. (C) Distribution of three subtypes of cervical cancers (Complete data is in Supplemental Table 2). (D) TCGA CC patients with YAP1 amplification, adjusted for clinical stage, had significantly worse survival outcomes than those without YAP1 amplification. (E) Survival curve for YAP1 -amplified CC in the Caris dataset. (F) Cervical cancer patient outcomes from completed Alpelisib (BYL-719) trials. The respective study and year are listed. PR = Partial Response; SD = Stable Disease.

Article Snippet: BYL-719, a potent and selective PI3Kα ( PIK3CA/ p110) inhibitor with IC50 of 5 nM, was purchased from MCE (Cat# HY-15244, MedChem Express).

Techniques: Amplification

Journal: Neoplasia (New York, N.Y.)

Article Title: PIK3CA mutant cervical cancer is selectively suppressed by PI3Kα inhibition (Alpelisib/BYL-719 and Inavolisib/GDC-0077) and cooperates with HPV directed T cell therapy

doi: 10.1016/j.neo.2026.101305

Figure Lengend Snippet: Inhibition of cervical cancer cell lines by PI3K α inhibitors. The maximum dose for each cell line was selected, and the percentage inhibition was compared with the corresponding control. (A) Alpelisib (BYL-719). (B) Inavolisib (GDC-0077). All cell lines have PIK3CA mutations except SiHa. **** = p < 0.0001 by one-way ANOVA and Dunnett’s multiple comparison test. <20% inhibition interpreted as no or negative response.

Article Snippet: BYL-719, a potent and selective PI3Kα ( PIK3CA/ p110) inhibitor with IC50 of 5 nM, was purchased from MCE (Cat# HY-15244, MedChem Express).

Techniques: Inhibition, Control, Comparison

Journal: Neoplasia (New York, N.Y.)

Article Title: PIK3CA mutant cervical cancer is selectively suppressed by PI3Kα inhibition (Alpelisib/BYL-719 and Inavolisib/GDC-0077) and cooperates with HPV directed T cell therapy

doi: 10.1016/j.neo.2026.101305

Figure Lengend Snippet: Impact of BYL-719 on the expression of target proteins in cervical cancer cell lines. ( A, B) CaSki cells treated with BYL-719 show reduced levels of PD-L1, YAP1, EGFR, CTGF, Integrin, and HPV16 E7. In Panel B cells were treated with 5uM BYL-719, washed at 24 h and place in 0, 1 or 5uM drug. (exposure time, 2 min). (C) BYL-719-treated ME180 cells show decreased levels of PD-L1 and CTGF. (D) SNU-17 cells also show reduced levels of these proteins after treatment (exposure time, 5 min). (E) SiHa ( PIK3CA WT) shows no reduction ofHPV16 E7 after treatment with BYL-719 (exposure time, 3 min). (F) Cell proliferation plot of SNU-17 cells treated with BYL-719. (G) SiHa cells treated with BYL719. *=P < 0.05, **=P < 0.01, ***=P < 0.001.

Article Snippet: BYL-719, a potent and selective PI3Kα ( PIK3CA/ p110) inhibitor with IC50 of 5 nM, was purchased from MCE (Cat# HY-15244, MedChem Express).

Techniques: Expressing

Journal: International Journal of Molecular Sciences

Article Title: Pregabalin Depresses Cerebellar Parallel Fiber–Purkinje Cell Synaptic Transmission by Modulating Glun2a-Containing Nmda Receptors in Mice In Vitro

doi: 10.3390/ijms27114660

Figure Lengend Snippet: The inhibitory effect of PGB on PF–PC synaptic transmission persisted following blockade of postsynaptic NMDA receptors but was abolished by disruption of the α 2 δ-1–NMDAR interaction. ( A ) Representative traces of evoked EPSCs in response to paired-pulse stimulation (0.2 ms pulse duration, 50 ms inter-pulse interval) under control conditions, during pregabalin (PGB; 10 μM) application, and following washout (recovery). Recordings were performed with MK-801-containing pipette solution (left) or following extracellular application of the α2δ-1 Tat peptide (right; 1 μM). ( B ) Pooled data showing normalized N1 amplitude under these conditions. ( C , D ) Bar graphs with individual data points illustrating normalized N1 amplitude ( C ) and paired-pulse ratio (PPR; ( D )) under these conditions. * p < 0.05 versus control; n = 8 cells/8 slices/5 mice for the MK-801 group; n = 8 cells/8 slices/6 mice for the α2δ-1 Tat peptide group.

Article Snippet: The α 2 δ-1 Tat peptide (VSGLNPSLWSIFGLQFILLWLVSGSRHYLW) was purchased from MedChemExpress LLC. (Shanghai, China).

Techniques: Transmission Assay, Disruption, Control, Transferring

Journal: International Journal of Molecular Sciences

Article Title: Pregabalin Depresses Cerebellar Parallel Fiber–Purkinje Cell Synaptic Transmission by Modulating Glun2a-Containing Nmda Receptors in Mice In Vitro

doi: 10.3390/ijms27114660

Figure Lengend Snippet: The effect of PGB on mEPSCs was prevented by blockade of GluN2A-containing NMDA receptors or disruption of α 2 δ-1–NMDA receptor coupling. ( A ) In the presence of a mixture of gabazine (20 μM), TTX (1 μM), and α2δ-1Tat peptide (1 μM), representative membrane current traces of a cerebellar PC recorded under control conditions, during pregabalin (PGB; 10 μM) application, and following washout (recovery). ( B , C ) In the presence of α2δ-1Tat peptide, cumulative probability–interevent interval curves ( B ) and cumulative probability–amplitude curves ( C ) of mEPSCs under control, PGB treatment, and recovery conditions. ( D , E ) Bar graphs showing the mean ± S.E.M. and individual data points for the normalized mEPSC frequency ( D ) and amplitude ( E ) in PCs in the presence of α2δ-1Tat peptide (1 μM; left panel) and PEAQX (1 µM; right panel) under each condition. n = 7 cells/7 slices/4 mice in PEAQX group; n = 7 cells/7 slices/6 mice in α2δ-1Tat peptide group.

Article Snippet: The α 2 δ-1 Tat peptide (VSGLNPSLWSIFGLQFILLWLVSGSRHYLW) was purchased from MedChemExpress LLC. (Shanghai, China).

Techniques: Disruption, Membrane, Control

Journal: International Journal of Molecular Sciences

Article Title: Pregabalin Depresses Cerebellar Parallel Fiber–Purkinje Cell Synaptic Transmission by Modulating Glun2a-Containing Nmda Receptors in Mice In Vitro

doi: 10.3390/ijms27114660

Figure Lengend Snippet: Co-expression of α 2 δ-1 and GluN2A subunits in the molecular layer of the mouse cerebellum. ( A ) Left panel: confocal micrograph showing DAPI staining (blue) in the mouse cerebellar cortex; right panel: magnified view of DAPI staining (blue) corresponding to the boxed area in the left panel. DAPI is a blue nucleic acid dye that preferentially stains double-stranded DNA (dsDNA) in cells. ( B ) Higher-magnification images of the boxed area in the right panel of ( A ), showing DAPI staining (blue), α 2 δ-1 subunit immunoreactivity (red), GluN2A immunoreactivity (green), and the merged immunofluorescence image in the Purkinje cell layer (PCL) and molecular layer (ML). Red fluorescence signals for the α 2 δ-1 subunit and green fluorescence signals for GluN2A immunoreactivity were detected in the ML, surrounding the dendrites of PCs. ML, molecular layer; PCL, Purkinje cell layer; GCL, granular cell layer. ( C ) Co-immunoprecipitation analysis revealed the protein–protein interaction between α 2 δ-1 and NMDAR in membrane extracts from the molecular layer of the cerebellar cortex. Proteins were first immunoprecipitated with rabbit anti-GluN1, anti-α 2 δ-1, or control IgG antibodies. Western immunoblotting (IB) was then performed using mouse anti-α 2 δ-1 (upper panel) and anti-GluN2A antibodies (lower panel). IgG and input samples (tissue lysates without immunoprecipitation) served as the negative and positive controls, respectively.

Article Snippet: The α 2 δ-1 Tat peptide (VSGLNPSLWSIFGLQFILLWLVSGSRHYLW) was purchased from MedChemExpress LLC. (Shanghai, China).

Techniques: Expressing, Staining, Immunofluorescence, Fluorescence, Immunoprecipitation, Membrane, Control, Western Blot