Use of Essential Medicines for Pain Relief and Palliative Care: A Global Consensus Process.

Context: The WHO Model List of Essential Medicines includes 24 medications under the section Medicines for Pain and Palliative Care (EML). The Lancet Commission on Pain and Palliative Care developed the Lancet Essential Package (LEP), including 35 medications designed to alleviate serious health-related suffering worldwide.

Objectives: This study aims to provide recommendations on the appropriate use of essential of medicines in palliative care.

A pilot trial of neoadjuvant pyrotinib plus trastuzumab, dalpiciclib, and letrozole for triple-positive breast cancer.

Triple-positive breast cancer (TPBC) poorly responds to current standard neoadjuvant therapy (trastuzumab plus pertuzumab and chemotherapy). Our previous MUKDEN 01 study showed a promising total pathological complete response (tpCR) rate of 30.4% with neoadjuvant pyrotinib (pan-human epidermal growth factor receptor tyrosine kinase inhibitor) plus dalpiciclib (cyclin-dependent kinase 4/6 inhibitor) and letrozole, but the efficacy remains suboptimal.

Nanoemulsions: Summary of a Decade of Research and Recent Advances.

Nanoemulsions consist of a combination of several components such as oil, water, emulsifiers, surfactants and cosurfactants. Various techniques for producing nanoemulsions include high-energy and low-energy approaches such as high-pressure homogenization, microfluidization, jet disperser and phase inversion methods. The properties of a formulation can be influenced by elements such as the composition, concentration, size and charge of droplets, which in turn can affect the technique of manufacture.

Inhibition of YAP1 activity ameliorates acute lung injury through promotion of M2 macrophage polarization.

The balance of M1/M2 macrophage polarization plays an important role in regulating inflammation during acute lung injury (ALI). Yes-associated protein (YAP1) is a key protein in the Hippo-YAP1 signaling pathway and is involved in macrophage polarization. We aimed to determine the role of YAP1 in pulmonary inflammation following ALI and regulation of M1/M2 polarization.

Understanding and targeting resistance mechanisms in cancer.

Resistance to cancer therapies has been a commonly observed phenomenon in clinical practice, which is one of the major causes of treatment failure and poor patient survival. The reduced responsiveness of cancer cells is a multifaceted phenomenon that can arise from genetic, epigenetic, and microenvironmental factors. Various mechanisms have been discovered and extensively studied, including drug inactivation, reduced intracellular drug accumulation by reduced uptake or increased efflux, drug target alteration, activation of compensatory pathways for cell survival, regulation of DNA repair and cell death, tumor plasticity, and the regulation from tumor microenvironments (TMEs).

Inhaled Indomethacin-Loaded Liposomes as Potential Therapeutics against Non-Small Cell Lung Cancer (NSCLC).

Most lung cancer instances are non-small cell lung cancers (NSCLC). As stated by recent literature, cycloxygenase-2 (COX-2) is upregulated in lung adenocarcinomas. COX-2 relates to enhanced cell proliferation and reduced apoptosis; both of which are essential for an invasive tumor growth and metastasis.

Overcoming multidrug resistance by knockout of ABCB1 gene using CRISPR/Cas9 system in SW620/Ad300 colorectal cancer cells.

Multidrug resistance (MDR) has been extensively reported in colorectal cancer patients, which remains a major cause of chemotherapy failure. One of the critical mechanisms of MDR in colorectal cancer is the reduced intracellular drug level led by the upregulated expression of the ATP-binding cassette (ABC) transporters, particularly, ABCB1/P-gp. In this study, the CRISPR/Cas9 system was utilized to target in MDR colorectal cancer SW620/Ad300 cell line with ABCB1 overexpression.

Insights on the structure-function relationship of human multidrug resistance protein 7 (MRP7/ABCC10) from molecular dynamics simulations and docking studies.

ATP-binding cassette (ABC) transporters superfamily mediates multidrug resistance in cancer by extruding structurally distinct chemotherapeutic agents, causing failure in chemotherapy. Among the 49 ABC transporters, multidrug resistance protein 7 (MRP7 or ABCC10) is relatively new and has been identified as the efflux pump of multiple anticancer agents including alkaloids and taxanes. Herein, we construct and validate a homology model for human MRP7 based on the cryo-EM structures of MRP1.

Association between Etomidate Use for Rapid Sequence Intubation and Adrenal Insufficiency in Sepsis.

Background The risk of adrenal insufficiency (AI) in using single-dose etomidate for intubation among patients with sepsis remains controversial. Our aim was to assess the prevalence of AI and characterize the risk factors in patients who received etomidate for rapid sequence intubation (RSI). Methods This is a retrospective study of prospectively-acquired data evaluating surgical intensive care unit (SICU) patients who developed respiratory failure undergoing RSI.

Repurposing Quinacrine for Treatment of Malignant Mesothelioma: In-Vitro Therapeutic and Mechanistic Evaluation.

Malignant mesothelioma (MM) is a rare type of cancer primarily affecting mesothelial cells lining the pleural cavity. In this study, we propose to repurpose quinacrine (QA), a widely approved anti-malarial drug, for Malignant Pleural Mesothelioma (MPM) treatment. QA demonstrates high degree of cytotoxicity against both immortalized and primary patient-derived cell lines with sub-micromolar 50% inhibitory concentration (IC) values ranging from 1.

Development of pharmaceutically scalable inhaled anti-cancer nanotherapy - Repurposing amodiaquine for non-small cell lung cancer (NSCLC).

New drug and dosage form development faces significant challenges, especially in oncology, due to longer development cycle and associated scale-up complexities. Repurposing of existing drugs with potential anti-cancer activity into new therapeutic regimens provides a feasible alternative. In this project, amodiaquine (AQ), an anti-malarial drug, has been explored for its anti-cancer efficacy through formulating inhalable nanoparticulate systems using high-pressure homogenization (HPH) with scale-up feasibility and high reproducibility.

Combination of cyclophosphamide and shengbai decoction has synergistic effect against melanoma.

Shengbai decoction (SBD), a famous Chinese herbal prescription, has been used for treatment of leukopenia for decades in China. In this study, its synergistic antitumor effect in combination with cyclophosphamide (CTX) on melanoma-bearing mice was investigated. A total of forty C57BL/6 male mice successfully modeled (6-8 weeks old, 18-22 g) were randomly divided into 4 groups (n = 10): 1) the model group, 2) the CTX group, 3) the low dose of SBD (10.

Fondaparinux Sodium Compared With Low-Molecular-Weight Heparins for Perioperative Surgical Thromboprophylaxis: A Systematic Review and Meta-analysis.

Background Fondaparinux sodium has been compared with low-molecular-weight heparins ( LMWH ) in randomized controlled trials for perioperative surgical thromboprophylaxis. However, the results from these studies are inconsistent in terms of efficacy and safety to reach a clinical decision. The objective of this study was to systematically review the randomized controlled trials comparing the efficacy and safety of fondaparinux and LMWH for perioperative surgical thromboprophylaxis.

Repurposing N,N-Dimethylacetamide (DMA), a Pharmaceutical Excipient, as a Prototype Novel Anti-inflammatory Agent for the Prevention and/or Treatment of Preterm Birth.

Background: Preterm birth (PTB), or birth that occurs before 37 weeks of gestation, accounts for the majority of perinatal morbidity and mortality. As of 2016, PTB has an occurrence rate of 9.6% in the United States and accounts for up to 18 percent of births worldwide.

Exploitation of Novel Molecular Targets to Treat Idiopathic Pulmonary Fibrosis: A Drug Discovery Perspective.

Background: Idiopathic pulmonary fibrosis (IPF) is the most common fibrosing lung disease and is caused by excessive lung scarring. IPF-associated severe mortality can be attributed to late diagnosis due to its generic symptoms, and more importantly due to the lack of effective therapies available. Despite extensive research in the past decades, lung transplant still remains the most effective treatment for IPF.