Development of a dexamethasone-hyaluronic acid conjugate with selective targeting effect for acute lung injury therapy.

Acute lung injury (ALI), a critical complication of COVID-19, is characterized by widespread inflammation and severe pulmonary damage, necessitating intensive care for those affected. Although glucocorticoids (GCs), such as dexamethasone (Dex), have been employed clinically to lower mortality, their nonspecific systemic distribution has led to significant side effects, limiting their use in ALI treatment. In this study, we explored the conjugation of Dex to hyaluronic acid (HA) to achieve targeted delivery to inflamed lung tissues.

Development of a zinc chloride-based chemo-mechanical system for potential minimally invasive dental caries removal system.

Background/purpose: The chemo-mechanical caries-removal technique is known to offer advantages of selective dentin caries treatment while leaving healthy dental tissues intact. However, current sodium hypochlorite based reagents usually excessively damage dentin collagen. Therefore, the purpose of this study was to develop a novel chemo-mechanical caries-removal system to preserve the collagen network for subsequent prosthetic restorations.

Development of triamcinolone acetonide-hyaluronic acid conjugates with selective targeting and less osteoporosis effect for rheumatoid arthritis treatments.

Rheumatoid arthritis (RA) is a common systemic autoimmune disease in developed countries. In clinical treatment, steroids have been used as bridging and adjunctive therapy after disease-modifying anti-rheumatic drug administration. However, the severe side effects caused by the nonspecific targeting of organs followed by long-term administration have limited their usage in RA.

Monitoring of T790M in plasma ctDNA of advanced EGFR-mutant NSCLC patients on first- or second-generation tyrosine kinase inhibitors.

Background: The T790M mutation is the major resistance mechanism to first- and second-generation TKIs in EGFR-mutant NSCLC. This study aimed to investigate the utility of droplet digital PCR (ddPCR) for detection of T790M in plasma circulating tumor DNA (ctDNA), and explore its impact on prognosis.

Methods: This prospective study enrolled 80 advanced lung adenocarcinoma patients treated with gefitinib, erlotinib, or afatinib for TKI-sensitizing mutations between 2015 and 2019.

The Optimal Primary Treatment for Pediatric Perianal Abscess and Anal Fistula: A Systemic Review and Meta-Analysis.

Background: Perianal abscesses and anal fistulas are common. The principle of intention-to-treat has not been considered in previous systemic reviews. Thus, the comparison between primary and post-recurrence management was confused, and the recommendation of primary treatment is obscure.

Co-location with marketing value activities as manufacturing upgrading in a COVID-19 outbreak era.

Co-location has been a relevant topic in the international business literature, yet the extant literature focuses on the co-location of research and development (R&D) and production activities and overlooks marketing value activities. Marketing innovation is an agile and effective way to respond to crises such as the COVID-19 pandemic, and many manufacturers in global value chains aim to upgrade functionally following the trajectory of the OEM-ODM-OBM. Thus, this study proposes the co-location of marketing activities as a flexible and organizational learning strategy for manufacturing upgrades, and explores the antecedents of marketing co-location in foreign direct investment (FDI) decisions.

Molecular Characterization and Pathogenicity of the Novel Recombinant Muscovy Duck Parvovirus Isolated from Geese.

Goose parvovirus (GPV) and Muscovy duck parvovirus (MDPV) are the main agents associated with waterfowl parvovirus infections that caused great economic losses in the waterfowl industry. In 2020, a recombinant waterfowl parvovirus, 20-0910G, was isolated in a goose flock in Taiwan that experienced high morbidity and mortality. The whole genome of 20-0910G was sequenced to investigate the genomic characteristics of this isolate.

Hyaluronic Acid-Glycine-Cholesterol Conjugate-Based Nanoemulsion as a Potent Vaccine Adjuvant for T Cell-Mediated Immunity.

Clinical cases of allergic reaction that are due to excipients containing polyethylene glycol (PEG), a hydrophilic molecule commonly used in drug/vaccine formulations, has attracted much attention in recent years. In order to develop PEG-free adjuvants, we investigated the feasibility of natural ingredients in the human body such as hyaluronic acid in the form of hyaluronic acid-glycine cholesterol (HACH) conjugate as an excipient for vaccine formulation. Interestingly, HACH grafted with ~13 wt.

Effects of Eye Drops Containing Hyaluronic Acid-Nimesulide Conjugates in a Benzalkonium Chloride-Induced Experimental Dry Eye Rabbit Model.

Dry eye syndrome (DES) is a common ocular disease worldwide. Currently, anti-inflammatory agents and immunosuppressive drugs, such as cyclosporine A, have been widely used to treat this chronic condition. However, the multifactorial etiology of DES, poor tolerance, low bioavailability, and prolonged treatment to response time have limited their usage.

Vorinostat combined with brigatinib overcomes acquired resistance in EGFR-C797S-mutated lung cancer.

The development of a new generation of tyrosine kinase inhibitors (TKIs) has improved the treatment response in lung adenocarcinomas. However, acquired resistance often occurs due to new epidermal growth factor receptor (EGFR) mutations. In particular, the C797S mutation confers drug resistance to T790M-targeting EGFR TKIs.

EGFR-Mutant SCLC Exhibits Heterogeneous Phenotypes and Resistance to Common Antineoplastic Drugs.

Introduction: Approximately 5% of patients with EGFR-activating mutations acquire EGFR tyrosine kinase inhibitor (TKI) resistance through SCLC transformation. However, the reason for the poor outcome and the molecular basis of EGFR-mutant SCLC that has transformed from adenocarcinoma remain unclear.

Methods: In this study, we established two EGFR-mutant SCLC cell lines from lung adenocarcinoma patients after failed EGFR-TKI treatment to investigate their molecular basis and potential therapeutic strategies in the hope of improving patient outcome.

Hyaluronic acid-nimesulide conjugates as anticancer drugs against CD44-overexpressing HT-29 colorectal cancer in vitro and in vivo.

Carrier-mediated drug delivery systems are promising therapeutics for targeted delivery and improved efficacy and safety of potent cytotoxic drugs. Nimesulide is a multifactorial cyclooxygenase 2 nonsteroidal anti-inflammatory drug with analgesic, antipyretic and potent anticancer properties; however, the low solubility of nimesulide limits its applications. Drugs conjugated with hyaluronic acid (HA) are innovative carrier-mediated drug delivery systems characterized by CD44-mediated endocytosis of HA and intracellular drug release.

Acquired BRAF V600E Mutation as Resistant Mechanism after Treatment with Osimertinib.

Introduction: AZD9291 (osimertinib) is designed for acquired T790M mutation after first- and second-generation EGFR) tyrosine kinase inhibitors have been used. Some of the resistance mechanisms that present after osimertinib treatment, including a newly acquired EGFR C797S mutation, have been identified. It is unclear, however, whether the bypass pathway is also a mechanism of resistance in patients after osimertinib treatment.

Hedgehog pathway maintains cell survival under stress conditions, and drives drug resistance in lung adenocarcinoma.

Hedgehog (HH) pathway plays an important role in embryonic development, but is largely inactive in adult except for tissue repair. Aberrant activation of HH pathway has been found in a variety of cancer types. In non-small cell lung cancer, however, the role and importance of HH pathway remain controversial.

Cystine Deprivation Triggers Programmed Necrosis in VHL-Deficient Renal Cell Carcinomas.

Oncogenic transformation may reprogram tumor metabolism and render cancer cells addicted to extracellular nutrients. Deprivation of these nutrients may therefore represent a therapeutic opportunity, but predicting which nutrients cancer cells become addicted remains difficult. Here, we performed a nutrigenetic screen to determine the phenotypes of isogenic pairs of clear cell renal cancer cells (ccRCC), with or without VHL, upon the deprivation of individual amino acids.

Comprehensive profiling of amino acid response uncovers unique methionine-deprived response dependent on intact creatine biosynthesis.

Besides being building blocks for protein synthesis, amino acids serve a wide variety of cellular functions, including acting as metabolic intermediates for ATP generation and for redox homeostasis. Upon amino acid deprivation, free uncharged tRNAs trigger GCN2-ATF4 to mediate the well-characterized transcriptional amino acid response (AAR). However, it is not clear whether the deprivation of different individual amino acids triggers identical or distinct AARs.

Cancer-associated fibroblasts regulate the plasticity of lung cancer stemness via paracrine signalling.

Cancer stem cells (CSCs) are a promising target for treating cancer, yet how CSC plasticity is maintained in vivo is unclear and is difficult to study in vitro. Here we establish a sustainable primary culture of Oct3/4(+)/Nanog(+) lung CSCs fed with CD90(+) cancer-associated fibroblasts (CAFs) to further advance our knowledge of preserving stem cells in the tumour microenvironment. Using transcriptomics we identify the paracrine network by which CAFs enrich CSCs through de-differentiation and reacquisition of stem cell-like properties.

Soluble triggering receptor expressed on myeloid cells-1 as an infection marker for patients with neutropenic fever.

Objective: To assess the value of soluble triggering receptor expressed on myeloid cells-1 as a biomarker of infection in patients with neutropenic fever comparing with procalcitonin and C-reactive protein.

Design: Prospective, comparative, single-center study.

Setting: Hematology ward at a university hospital.

Serum soluble triggering receptor expressed on myeloid cells-1 in acute respiratory distress syndrome: a prospective observational cohort study.

Background/purpose: Serum soluble triggering receptor expressed on myeloid cells-1 (sTREM-1), a detector of acute inflammatory response to microbial products and a good marker for diagnosing sepsis and pneumonia, has not yet been described as a predictor for infection or a prognostic factor in patients with acute respiratory distress syndrome (ARDS).

Methods: This prospective observational cohort study enrolled 63 ventilated adult patients with ARDS; 50 as septic and 13 as non-septic, and followed them for 28 days in intensive care units at a university hospital in Taiwan. Serial serum sTREM-1 levels and cytokines, such as interleukin (IL)-1, IL-8, and tumor necrosis factor-α, on days 1, 3, 5, 7 and 14 were measured by an enzyme-linked immunosorbent assay.

Structural and functional analyses of the 3' untranslated region of Bamboo mosaic virus satellite RNA.

The 3'-untranslated region (UTR) of RNA genomes of viruses and satellite RNAs plays essential roles in viral replication and transcription. The structural features of the 3'-UTR of the satellite RNA of Bamboo mosaic virus (satBaMV) involved in its replication were analyzed in this study. By the use of enzymatic probing, the secondary structure of satBaMV 3'-UTR was confirmed to comprise two small stem-loops (SLA and SLB), one large stem-loop (SLC), and a poly(A) tail of mainly 75-200 adenylate residues, which is similar to those on the genomic RNA of the helper virus, BaMV.