Triple Combination of MEK, BET, and CDK Inhibitors Significantly Reduces Human Malignant Peripheral Nerve Sheath Tumors in Mouse Models.

Purpose: Malignant peripheral nerve sheath tumor (MPNST) is an aggressive soft tissue sarcoma that develops sporadically or in Neurofibromatosis type 1 patients. Its development is marked by the inactivation of specific tumor suppressor genes (TSGs): NF1, CDKN2A and SUZ12EED (Polycomb Repressor Complex 2). Each TSG loss can be targeted by particular drug inhibitors and we aimed to systematically combine these inhibitors, guided by TSG inactivation status, to test their precision medicine potential for MPNSTs.

Delivery of Magnolia bark extract in nanoemulsions formed by high and low energy methods improves the bioavailability of Honokiol and Magnolol.

Honokiol (HK) and Magnolol (MG), isomers found in Magnolia officinalis bark extract (MBE), possess bioactive properties attributed to their biphenolic structure. However, their low polarity results in poor oral absorption, limiting their bioavailability. To enhance their systemic absorption after passing through the digestive tract, efficient carrier systems are essential.

Chronic spontaneous urticaria remission definition and therapy stepping-down. WAO Position Paper.

Background: There is no global agreement on the definition of Chronic Spontaneous Urticaria (CSU) remission.

Objective: To generate a consensus for clinical definitions in CSU focused on remission.

Methods: The World Allergy Organization (WAO) Urticaria Committee systematically reviewed current available longitudinal articles.

Identification of potent HSV antivirals using 3D bioprinted human skin equivalents.

Herpes simplex virus (HSV) infection has worldwide public health concerns and lifelong medical impacts. The standard therapy, acyclovir, has limited efficacy in preventing HSV subclinical virus shedding, and drug resistance occurs in immunocompromised patients, highlighting the need for novel therapeutics. HSV infection manifests in the skin epidermal layer, but current drug discovery utilizes Vero cells and fibroblasts monolayer cultures, capturing neither relevance nor tissue environment.

Association between Driving Pressure, Systemic Inflammation and Non-pulmonary Organ Dysfunction in Patients with Acute Respiratory Distress Syndrome, a Prospective Pathophysiological Study.

Background: Driving pressure is thought to determine the effect of low tidal ventilation on survival in patients with acute respiratory distress syndrome. The leading cause of mortality in these patients is non-pulmonary multiorgan dysfunction, which is believed to worsen due to the biological response to mechanical ventilation (biotrauma). Therefore, we aimed to analyze the association between driving pressure, biotrauma, and non-pulmonary multiorgan dysfunction.