RESUMEN

BACKGROUND: Over the past 15 years, World Neurosurgery (WN) has emerged as a pivotal source in the neurosurgery field, reflecting remarkable growth and development. Originally published as Surgical Neurology from 1973 to 2009, the journal transitioned to its current title in 2010, significantly expanding its reach and influence. METHODS: A comprehensive bibliometric analysis of WN's publications from 1973 to 2023 was performed. The analysis focused on identifying the top authors, universities, countries, and sponsors in two periods: 1973-2009 and 2010-2023. Additionally, the study included a detailed examination of the top 1,000 most cited papers, and summary of top 10 most cited papers. RESULTS: The analysis revealed that during the Surgical Neurology period, 6,567 research documents were published, including 6,503 articles and 64 reviews. Since rebranding as World Neurosurgery, the journal has published an additional 17,663 documents, comprising 15,366 articles and 2,297 reviews up to 2023. The top contributors (authors, universities, and sponsors) were identified, and the study found that WN has successfully increased its foothold across various continents. The co-word analysis provided insights into the thematic focus of the top 1,000 most cited papers, categorizing them into 15 distinct areas. CONCLUSION: This study underscores World Neurosurgery's significant role in advancing neurosurgical research over the past five decades. The findings highlight the journal's evolution, its expanding global influence, and the key contributors to its success.

RESUMEN

Background: Research on Coffea arabica focuses on various aspects, including genetics, breeding, climate change resilience, pest and disease management, agronomy, sensory analysis, and sustainability. This study aims to analyze the hotspots, conceptual map and dynamicity, global landscape, and emerging trends in Coffea arabica research (CA-R). Methods: A comprehensive dataset comprising data-driven articles (N = 3967) from 1932 to 2023 was extracted from Scopus using predefined search terms. VOSviewer and Bibliometrix applications were utilized to analyze the data. Thematic evolution was examined by identifying shifts in research focus over time. The global landscape was assessed by examining comparative productivity and collaborative dynamics. Highly-cited CA-R was identified to highlight key findings in specific research areas. Results: The analysis revealed a steady growth of CA-R (annual growth rate = 6.53 %), with strong international collaboration (international co-authorships = 29.35 %) and significant contributions from various countries. Brazil leads the way with 1601 publications, accounting for 28.55 % of the total. Recognizable CA-R focused on important areas such as pollination, shade management, nanotechnology applications, roasting effects, disease management, and environmental impacts. Thematic analysis identified five distinct clusters representing different CA-R themes: "coffee", "coffea," "fermentation," "Coffea arabica," and "climate change." Emerging themes such as "in vitro culture," "sustainable agriculture," "climate change," and "coffee berry borer" were also identified. Conclusion: The current findings enhance our understanding of CA-R and lay the groundwork for future studies in the coffee industry.

RESUMEN

The project aimed to conduct an up-to-date and comprehensive bibliometric analysis of robotic surgery to provide a detailed and holistic understanding of the field. Three strategies were employed in the data analysis i.e. search terms were explored in (A) the title, abstract, and keywords and (B) only in the title of the documents. In 3rd part we analyzed the top 100 most cited papers. Vosviewer and R Studio were utilized for detailed bibliometric and network analyses. Strategy one identified 38,469 publications, and strategy two identified 6451 publications from 2001 to 2023. The top authors, universities, countries, sponsors, and sources based on the number of publications were identified for both strategies. The top 100 most cited papers were analyzed, providing the annual number of publications and various citation metrics. Top authors (by number of publications, total citations, h-index, g-index, and m-index), universities, and countries within these highly cited papers, along with their co-authorship networks and dynamics, were examined. Co-words analysis of the top 100 most cited papers revealed the primary focus of these documents across 25 categories. This comprehensive bibliometric analysis of robotic surgery highlighted significant contributions and collaborations in the field, emphasizing the importance of global and collaborative efforts in advancing robotic surgery research.

Asunto(s)

RESUMEN

Molecular glue (MG) compounds are a type of unique small molecule that can change the protein-protein interactions (PPIs) and interactomes by degrading, stabilizing, or activating the target protein after their binging. These small-molecule MGs are gradually being recognized for their potential application in treating human diseases, including cancer. Evidence suggests that small-molecule MG compounds could essentially target any proteins, which play critical roles in human disease etiology, where many of these protein targets were previously considered undruggable. Intriguingly, most MG compounds with high efficacy for cancer treatment can glue on and control multiple key protein targets. On the other hand, a single key protein target can also be glued by multiple MG compounds with distinct chemical structures. The high flexibility of MG-protein interaction profiles provides rich soil for the growth and development of small-molecule MG compounds that can be used as molecular tools to assist in unraveling disease mechanisms, and they can also facilitate drug development for the treatment of human disease, especially human cancer. In this review, we elucidate this concept by using various types of small-molecule MG compounds and their corresponding protein targets that have been documented in the literature.

Asunto(s)

RESUMEN

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC), a difficult-to-treat cancer, is expected to become the second-largest cause of cancer-related deaths by 2030, while colorectal cancer (CRC) is the third most common cancer and the third leading cause of cancer deaths. Currently, there is no effective treatment for PDAC patients. The development of novel agents to effectively treat these cancers remains an unmet clinical need. FL118, a novel anticancer small molecule, exhibits high efficacy against cancers; however, the direct biochemical target of FL118 is unknown. METHODS: FL118 affinity purification, mass spectrometry, Nanosep centrifugal device and isothermal titration calorimetry were used for identifying and confirming FL118 binding to DDX5/p68 and its binding affinity. Immunoprecipitation (IP), western blots, real-time reverse transcription PCR, gene silencing, overexpression (OE) and knockout (KO) were used for analysing gene/protein function and expression. Chromatin IP was used for analysing protein-DNA interactions. The 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromid assay and human PDAC/CRC cell/tumour models were used for determining PDAC/CRC cell/tumour in vitro and in vivo growth. RESULTS: We discovered that FL118 strongly binds to dephosphorylates and degrades the DDX5 oncoprotein via the proteasome degradation pathway without decreasing DDX5 mRNA. Silencing and OE of DDX5 indicated that DDX5 is a master regulator for controlling the expression of multiple oncogenic proteins, including survivin, Mcl-1, XIAP, cIAP2, c-Myc and mutant Kras. Genetic manipulation of DDX5 in PDAC cells affects tumour growth. PDAC cells with DDX5 KO are resistant to FL118 treatment. Our human tumour animal model studies further indicated that FL118 exhibits high efficacy to eliminate human PDAC and CRC tumours that have a high expression of DDX5, while FL118 exhibits less effectiveness in PDAC and CRC tumours with low DDX5 expression. CONCLUSION: DDX5 is a bona fide FL118 direct target and can act as a biomarker for predicting PDAC and CRC tumour sensitivity to FL118. This would greatly impact FL118 precision medicine for patients with advanced PDAC or advanced CRC in the clinic. FL118 may act as a 'molecular glue degrader' to directly glue DDX5 and ubiquitination regulators together to degrade DDX5.

Asunto(s)

RESUMEN

The incidence of renal cell carcinoma (RCC) is increasing worldwide with an approximate 20% mortality rate. The challenge in RCC is the therapy-resistance. Cancer resistance to treatment employs multiple mechanisms due to cancer heterogeneity with multiple genetic and epigenetic alterations. These changes include aberrant overexpression of (1) anticancer cell death proteins (e.g., survivin/BIRC5), (2) DNA repair regulators (e.g., ERCC6) and (3) efflux pump proteins (e.g., ABCG2/BCRP); mutations and/or deregulation of key (4) oncogenes (e.g., MDM2, KRAS) and/or (5) tumor suppressor genes (e.g., TP5/p53); and (6) deregulation of redox-sensitive regulators (e.g., HIF, NRF2). Foci of tumor cells that have these genetic alterations and/or deregulation possess survival advantages and are selected for survival during treatment. We will review the significance of survivin (BIRC5), XIAP, MCL-1, HIF1α, HIF2α, NRF2, MDM2, MDM4, TP5/p53, KRAS and AKT in treatment resistance as the potential therapeutic biomarkers and/or targets in RCC in parallel with our analized RCC-relevant TCGA genetic results from each of these gene/protein molecules. We then present our data to show the anticancer drug FL118 modulation of these protein targets and RCC cell/tumor growth. Finally, we include additional data to show a promising FL118 analogue (FL496) for treating the specialized type 2 papillary RCC.

Asunto(s)

RESUMEN

Tumor heterogeneity in key gene mutations in bladder cancer (BC) is a major hurdle for the development of effective treatments. Using molecular, cellular, proteomics and animal models, we demonstrated that FL118, an innovative small molecule, is highly effective at killing T24 and UMUC3 high-grade BC cells, which have Hras and Kras mutations, respectively. In contrast, HT1376 BC cells with wild-type Ras are insensitive to FL118. This concept was further demonstrated in additional BC and colorectal cancer cells with mutant Kras versus those with wild-type Kras. FL118 strongly induced PARP cleavage (apoptosis hallmark) and inhibited survivin, XIAP and/or Mcl-1 in both T24 and UMUC3 cells, but not in the HT1376 cells. Silencing mutant Kras reduced both FL118-induced PARP cleavage and downregulation of survivin, XIAP and Mcl-1 in UMUC3 cells, suggesting mutant Kras is required for FL118 to exhibit higher anticancer efficacy. FL118 increased reactive oxygen species (ROS) production in T24 and UMUC3 cells, but not in HT1376 cells. Silencing mutant Kras in UMUC3 cells reduced FL118-mediated ROS generation. Proteomics analysis revealed that a profound and opposing Kras-relevant signaling protein is changed in UMUC3 cells and not in HT1376 cells. Consistently, in vivo studies indicated that UMUC3 tumors are highly sensitive to FL118 treatment, while HT1376 tumors are highly resistant to this agent. Silencing mutant Kras in UMUC3 cell-derived tumors decreases UMUC3 tumor sensitivity to FL118 treatment. Together, our studies revealed that mutant Kras is a favorable biomarker for FL118 targeted treatment.