1,721,121 research outputs found
Orchestrating Cytosolic Access: The Partnership of Cationic Lytic Peptide L17E and Potassium Channel KCa3.1
No full textIn this issue of Molecular Therapy, the study by Kuriyama et al.1 represents an advance in the field of intracellular delivery systems by elucidating a novel mechanism for cytosolic delivery mediated by a cationic amphiphilic lytic peptide L17E (IWLTALKFLGKHAAKHEAKQQLSKL-amide). The investigators demonstrate that the peptide achieves cytosolic delivery primarily through transient plasma membrane disruption, bypassing some of the endocytic pathways, and highlight the pivotal role of the calcium-activated potassium channel KCa3.1, encoded by the gene KCNN4, in facilitating this process. These findings offer a deeper understanding of peptide-mediated delivery using a potassium channel and raise intriguing questions about the broader implications for drug delivery strategies
Protein Kinase Inhibitors in Drug Discovery
No full textThis chapter explores the ways in which protein kinase inhibitors perform.https://digitalcommons.chapman.edu/pharmacy_books/1001/thumbnail.jp
Inflammation and Detection: Rethinking the Biomarker Landscape in Gastric Cancer
Full text linkGastric carcinoma is a leading cause of cancer-related mortality worldwide, yet reliable noninvasive biomarkers for its early detection remain limited. As research continues to elucidate the inflammatory underpinnings of tumor initiation and progression, it has become increasingly clear that pro-inflammatory cytokines may hold promise as diagnostic adjuncts. Serum cytokines such as interleukin (IL)-1β, IL-6, IL-8, and interferon-gamma have been frequently reported as elevated in gastric cancer patients compared to healthy individuals. These molecules, known for their roles in modulating tumor-promoting inflammation, angiogenesis, and immune evasion, may serve as accessible indicators of disease presence or progression. Several studies have shown that individual cytokines, particularly IL-6 and IL-8, can achieve receiver operating characteristic curves and area under the curve values exceeding 0.70, suggesting reasonable diagnostic utility. We assess the comparative utility of individual cytokines versus multiplex panels, evaluate their roles in tumor biology and treatment resistance, and situate these findings within the broader inflammatory biomarker landscape. Limitations of the current literature, including small sample sizes, heterogeneity in study design, and lack of specificity, are critically discussed. We advocate for prospective, multicenter validation studies and highlight the promise of integrating inflammatory cytokine profiling into diagnostic algorithms. Composite cytokine panels may better reflect the complex immunobiology of tumor progression and offer a scalable, accessible adjunct to current gastric cancer screening strategies
Design strategies for protein kinase inhibitors
No full textDeregulation of protein kinases due to mutation or overexpression is a hallmark of several diseases, for example, cancer, diabetes, inflammation and cardiovascular disorders. Consequently, there has been a growing interest in the discovery of protein kinase inhibitors as novel drugs. Here, we focus on key milestones and advances in protein kinase inhibitor drug discovery over the last year, with an emphasis on novel strategies such as targeting of single and multiple binding sites, inactive conformations of kinases, allosteric sites, regulatory domains and heat shock proteins. We will highlight recent developments for specific inhibitors in clinical studies for growth factor receptors, non-receptor tyrosine kinases and serine/threonine kinases
Symmetrical Dinucleosides
Full text linkThe authors have reported the utility of 1 for the preparation of sulfonamides (J. Org. Chem. 2006, 71, 7915). To the best of the authors’ knowledge, this is the first report of the synthesis of 5¢,5¢-dinucleoside 5¢,5¢-phosphodiesters by using polymer-bound phosphitylating reagents
Swollen Lymph Node Metastasis in Gastric Cancer: A Forgotten Prognostic Signal in Need of Clinical Action
Full text linkGastric cancer (GC) remains a leading cause of cancer mortality. While the extent of nodal involvement is a well-known prognostic factor, the specific entity of swollen lymph node metastasis (SLNM), bulky nodal tumor deposits detectable radiologically or pathologically, has received little attention in staging. Recent data from a study by Cui et al demonstrated that SLNM is an independent predictor of very poor survival in GC. Through robust data and rigorous propensity-matched analyses, SLNM emerged not merely as an anatomical finding but as an independent predictor of poor prognosis, even among patients undergoing curative resection. As precision oncology advances, the findings by Cui et al urge a fundamental rethinking of how SLNM is incorporated into clinical decision-making for GC management. In this editorial, we critically examine the prognostic significance of SLNM, challenge its omission from traditional staging frameworks, and advocate for its formal integration into preoperative risk stratification and treatment planning. Recognizing SLNM at diagnosis could unlock intensified neoadjuvant therapy strategies and optimize outcomes for a historically high-risk patient subgroup
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Global Cancer Statistics 2022: The Trends Projection Analysis
Full text linkCancer is one of the most fatal diseases of recent times that causes several deaths every year. The disease variations in different parts of the world, the impact of available medical facilities, and other socio-economic factors have impacted the proper management of this disease. The comparative statistical data of cancer types like breast, prostate, colon, lung, lymph, blood, brain, and kidney cancers can be used to design treatment strategies and therapeutics development. With the advancement of science, several drugs besides diagnostic methods have emerged to control respective cancer and have assisted in curing this disease to some extent. The comparative statistics analysis for cancer about current prevalence is included here to bring a clear framework for the efforts towards future drug development to manage this disease. The availability of new diagnostics and therapeutics and advanced medical facilities in clinics impact cancer statistics. An evaluation of current trends and statistics of cancer pathology vis-à-vis theranostics (diagnostics as well as therapeutics) progress with possible application in clinical settings constitutes the core part of the discussion in this review
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
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