Elucidating novel signaling pathways that drive myotube hypertrophy may provide new insights into the mechanisms regulating skeletal muscle growth. We previously reported that 5-hydroxy-7-methoxyflavone (HMF) induces hypertrophy of murine C2C12 myotubes; however, the underlying molecular mechanism remains unclear. Here, loss- and gain-of-function analyses revealed that GPR97 positively regulates myotube size. Furthermore, knockdown and rescue experiments demonstrated that GPR97 is required for HMF-induced myotube hypertrophy. HMF activated mTORC1 signaling in myotubes, and intramuscular administration of HMF also activated mTORC1 signaling in mouse skeletal muscle in vivo. Gpr97 knockdown abolished HMF-induced mTORC1 signaling and protein synthesis. Furthermore, depletion of Gna12 and expression of dominant-negative Gα12 abolished HMF-induced myotube hypertrophy. Gna12 depletion also suppressed HMF-induced mTORC1 signaling and protein synthesis. Beclomethasone dipropionate, a reported GPR97 ligand, suppressed HMF-induced hypertrophy and mTORC1 signaling, while further enhancing HMF-induced serum response factor (SRF)-dependent transcription. Although dominant-negative RhoA inhibited HMF-induced SRF-dependent transcriptional activity, it did not affect myotube hypertrophy. These findings indicate that GPR97-Gα12-mTORC1 signaling promotes hypertrophy independent of the Gα12-RhoA-SRF pathway. GPR97 was predominantly expressed on the myotube surface as a C-terminal fragment generated by N-terminal fragment (NTF) cleavage, and HMF reduced its surface expression. HMF induced hypertrophy in myotubes expressing an NTF cleavage-resistant GPR97 mutant, but not in those expressing an NTF-deleted mutant. These results indicate that NTF cleavage is dispensable and suggest that NTF contributes to GPR97-mediated hypertrophic signaling. These findings identify a novel GPR97-Gα12-mTORC1 signaling axis that mediates HMF-induced myotube hypertrophy.

Single-inhaler triple therapy (SITT) combining an inhaled corticosteroid, long-acting β2-agonist, and long-acting muscarinic antagonist (ICS/LABA/LAMA) represents the current ceiling of inhaled pharmacotherapy for moderate-to-very-severe chronic obstructive pulmonary disease and severe uncontrolled asthma. Five device platforms are currently approved: two extrafine formulations delivering beclomethasone dipropionate/formoterol/glycopyrronium (the Modulite solution pressurised metered-dose inhaler [pMDI] and the NEXThaler breath-actuated dry powder inhaler [DPI]); the co-suspension pMDI Aerosphere platform (budesonide/glycopyrrolate/formoterol); the standard-particle Ellipta DPI (fluticasone furoate/umeclidinium/vilanterol); and the low-resistance, single-dose capsule-based DPI Breezhaler (mometasone furoate/indacaterol/glycopyrronium). Despite a shared pharmacological class, these systems differ in aerosol physics, particle engineering, intrapulmonary deposition patterns, and device-patient interaction. Furthermore, some of them are authorized only for COPD or asthma. This narrative review examines the technology and in vivo deposition evidence for each SITT platform, discusses real-world performance determinants (particle size, flow dependency, technique robustness), and proposes an expert-informed framework for patient-level device selection. Methodological limitations include reliance on in silico Functional Respiratory Imaging data when in vivo scintigraphy is unavailable, and inconsistent dose denominators across studies (emitted vs. metered dose). Cross-platform comparisons are limited by heterogeneous methodologies, and no SITT platform has demonstrated universal superiority. In platform-specific studies, NEXThaler shows relatively high lung deposition (∼55% of emitted dose) though flow-dependent; Aerosphere is robust to inhalation technique variations; Modulite provides extrafine, peripheral delivery; Ellipta and Breezhaler offer once-daily convenience with moderate deposition. Rational device selection requires structured assessment of patient inspiratory capacity, disease phenotype, coordination, and adherence. Head-to-head scintigraphy and prospective imaging-outcome studies represent major evidence gaps.

Chronic obstructive pulmonary disease (COPD) is a chronic lung disease associated with inflammation and obstruction of the airways. COPD progresses through 4 stages of increasing airflow limitation — mild, moderate, severe, and very severe — with symptoms and functional limitations worsening at each stage. Symptoms include difficulty in breathing, cough, and flare-ups (exacerbations) that may require hospitalization. As of 2022–2023, the prevalence of COPD was 8.74% in Canada.

C16-Methylcorticoids are important anti-inflammatory agents whose activity depends on the C16 methyl configuration. However, access to C16β analogues remains challenging. Herein, we report the first concise two-step stereoinversion of C16α-methylcorticoids to C16β diastereomers through C17 hydroxyl elimination followed by Mn-catalyzed Mukaiyama hydration. Betamethasone, beclomethasone, clobetasol, clobetamethasone, and difluorolaxone were obtained in useful yields with high diastereoselectivities (19 : 1 to >99 : 1 dr).

This study explores the application of secondary electrospray ionization mass spectrometry (SESI-MS) for the real-time characterization of pharmaceutical aerosols from metered-dose inhalers (MDIs). The analysis includes one of the most widely used inhalers worldwide, Ventolin®, a simple formulation containing salbutamol and norflurane for which salbutamol was reliably detected, while norflurane remained undetectable due to its low proton affinity; and Ventoduo®, a multicomponent formulation also including beclomethasone dipropionate, ethanol, and oleic acid for which all major components were successfully detected. The coupling of SESI with high-resolution MS enabled unambiguous identification of all analytes, with excellent mass accuracy, confirming the identity of both active ingredients through characteristic fragmentation patterns. These results demonstrate that SESI-MS, particularly when coupled with high-resolution instrumentation (SESI-HRMS), is a powerful and reliable tool for the comprehensive and real-time analysis of pharmaceutical aerosols, including those with multiple active ingredients and co-solvents.

Lenacapavir is now approved for highly treatment experienced persons living with HIV (PLWH) and for HIV pre-exposure prophylaxis (PrEP). Limited lenacapavir clinical data exist with real-world drug-drug interactions. We report two possible drug-drug interactions with ambulatory lenacapavir subcutaneous injections in two PLWH prescribed long-acting injection therapy. Case 1 describes a PLWH prescribed clopidogrel after an acute cerebrovascular event receiving an antiretroviral (ARV) regimen including subcutaneous lenacapavir and ibalizumab biweekly infusions. The clopidogrel was discontinued with no harm noted. Case 2 is a highly treatment experienced PLWH prescribed an ARV regimen including subcutaneous lenacapavir and intramuscular cabotegravir/rilpivirine injections on concomitant inhaled and nasal fluticasone. Symptoms consistent with adrenal insufficiency were reported with immediate fluticasone discontinuation and transition to beclomethasone. The patient's baseline cortisol concentration was low with improvement after fluticasone discontinuation. The electronic medical record alerts were customized to note these possible lenacapavir drug-drug interactions, similar to protease inhibitors/pharmacokinetic boosters (ritonavir and cobicistat) to prevent future events. This case series highlights possible lenacapavir drug-drug interactions and is a precautionary tale to other institutions to consider customizing electronic medical alerts for this novel long-acting injection.