Effects of essential oils on symptoms and course (duration and severity) of viral respiratory infections in humans: A rapid review.

Oral doses of certain essential oils may reduce symptoms of acute respiratory infections of viral origin. It is likely that the commercially available essential oil capsules Myrtol® (a mixture of essential oils of eucalyptus Eucalyptus globulus, sweet orange Citrus sinensis, myrtle Myrtus communis and lemon Citrus limonum) and Tavipec® (spike lavender Lavandula latifolia) could also provide mild to moderate symptom relief in patients with viral respiratory diseases. Myrtol® may also improve the course (duration and severity) of acute bronchitis of viral origin, in humans. Both products were well tolerated, with most of the mild to moderate side-effects affecting the gastrointestinal tract. This review found no research evidence describing the clinical effect of inhalation of essential oils for acute respiratory viral infections.

Clinical evidence from published clinical trials identified in this rapid review suggests that oral administration of blends of certain essential oils (EO) can reduce symptoms of acute respiratory infections of viral origin in humans, namely acute sinusitis and acute bronchitis.There is clinical evidence for orally administered Lavandula latifolia essential oil (Tavipec®) (n = 2) and a blend of essential oils of Eucalyptus globulus, Citrus sinensis, Myrtus communis and lemon Citrus limonum (Myrtol® and its successors GeloMyrtol® and GeloMyrtol®Forte) (n = 3) to reduce symptoms of acute sinusitis and acute bronchitis of viral origin(s) [[1], [2], [3], [4], [5]]. All five clinical trials relied mostly on (subjective) symptom scores to determine the treatment effect. Differences between treatment and placebo symptom scores in these clinical trials were statistically significant, although the differences in absolute numbers were small. Furthermore, clinical evidence suggests that Myrtol® is also able to improve the course (duration and severity) of acute bronchitis of viral origin, in humans [3,5].No clinical evidence was found on whether EO can also improve symptoms and/or course of other acute respiratory infections, like influenza or acute respiratory distress syndrome caused by viruses of the coronavirus class. Further clinical trials with these and other EO (or blends of EO), and other administration forms, like steam inhalation or personal inhalers, are warranted to further elucidate the potential of commonly available EOs in treating acute respiratory infections of viral origin, especially influenza and COVID-19.

Combined inhibition of receptor tyrosine and p21-activated kinases as a therapeutic strategy in childhood ALL.

Receptor tyrosine kinase (RTK)-dependent signaling has been implicated in the pathogenesis of acute lymphoblastic leukemia (ALL) of childhood. However, the RTK-dependent signaling state and its interpretation with regard to biological behavior are often elusive. To decipher signaling circuits that link RTK activity with biological output in vivo, we established patient-derived xenograft ALL (PDX-ALL) models with dependencies on fms-like tyrosine kinase 3 (FLT3) and platelet-derived growth factor receptor ß (PDGFRB), which were interrogated by phosphoproteomics using iTRAQ mass spectrometry. Signaling circuits were determined by receptor type and cellular context with few generic features, among which we identified group I p21-activated kinases (PAKs) as potential therapeutic targets. Growth factor stimulation markedly increased catalytic activities of PAK1 and PAK2. RNA interference (RNAi)-mediated or pharmacological inhibition of PAKs using allosteric or adenosine triphosphate (ATP)-competitive compounds attenuated cell growth and increased apoptosis in vitro. Notably, PAK1- or PAK2-directed RNAi enhanced the antiproliferative effects of the type III RTK and protein kinase C inhibitor midostaurin. Treatment of FLT3- or PDGFRB-dependent ALLs with ATP-competitive PAK inhibitors markedly decreased catalytic activities of both PAK isoforms. In FLT3-driven ALL, this effect was augmented by coadministration of midostaurin resulting in synergistic effects on growth inhibition and apoptosis. Finally, combined treatment of FLT3 D835H PDX-ALL with the ATP-competitive group I PAK inhibitor FRAX486 and midostaurin in vivo significantly prolonged leukemia progression-free survival compared with midostaurin monotherapy or control. Our study establishes PAKs as potential downstream targets in RTK-dependent ALL of childhood, the inhibition of which might help prevent the selection or acquisition of resistance mutations toward tyrosine kinase inhibitors.

The PML domain of PML-RARα blocks senescence to promote leukemia.

In most acute promyelocytic leukemia (APL) cases, translocons produce a promyelocytic leukemia protein-retinoic acid receptor α (PML-RARα) fusion gene. Although expression of the human PML fusion in mice promotes leukemia, its efficiency is rather low. Unexpectedly, we find that simply replacing the human PML fusion with its mouse counterpart results in a murine PML-RARα (mPR) hybrid protein that is transformed into a significantly more leukemogenic oncoprotein. Using this more potent isoform, we show that mPR promotes immortalization by preventing cellular senescence, impeding up-regulation of both the p21 and p19(ARF) cell-cycle regulators. This induction coincides with a loss of the cancer-associated ATRX/Daxx-histone H3.3 predisposition complex and suggests inhibition of senescence as a targetable mechanism in APL therapy.