Foundation For Clinical Research Research Articles

BIOM-07. SURVIVAL-ASSOCIATED GENETIC VARIATIONS IN TAIWANESE GLIOBLASTOMA MULTIFORME PATIENTS - A RETROSPECTIVE NGS STUDY

Abstract This retrospective study, conducted at Taichung Veterans General Hospital in Taiwan, employed Next-Generation Sequencing (NGS) technology to analyze genetic variations associated with survival in patients with glioblastoma multiforme (GBM). The study encompassed 30 newly diagnosed GBM patients, divided into two groups based on survival duration: long-term (over two years) and short-term (under two years). The findings are outlined below: Key Mutations: Significant mutations included CHEK2, IDH1, and TP53, along with variations in the TERT promoter and TP53 RNA splicing sites. Correlation Between Mutations and Survival: Contrary to Western data, TP53 mutations were more prevalent in the long-term survival group, suggesting that regional genetic differences may influence GBM prognosis. Therapeutic Effectiveness: The application of bevacizumab was significantly associated with improved survival rates, indicating its potential efficacy in treatment. The study highlights the critical role of personalized medicine in the treatment of GBM in Taiwan and points to the necessity of further research into the genetic characteristics and treatment responses of GBM patients in Taiwan and potentially other non-Western regions. These insights underline the importance of continuing to explore effective personalized treatment strategies and enhancing our understanding of genetic determinants in diverse populations. Moreover, the prevalence of certain mutations in Taiwanese patients, which differ from those commonly observed in Western populations, prompts a reevaluation of global treatment frameworks and suggests the potential for region-specific therapeutic protocols. The implication of these findings extends beyond immediate clinical applications, providing a foundation for future clinical trials and research into genetic markers that could dictate treatment choices. In conclusion, this study not only underscores the importance of individualized treatment plans based on genetic profiling but also highlights the variations in genetic mutations across different populations, which could have profound implications for the management of GBM worldwide. Further investigation into these disparities and their implications on treatment efficacy is essential for advancing GBM treatment and improving patient outcomes globally.

Phenolics in soymilk manufactured from black and Proto soybeans by two continuous-ultrahigh-temperature-processing technologies inhibit DU145-prostate cancer cell proliferation through apoptosis.

Plant genotypes and processing technologies affect health properties of foods. How thermal processes with different sterilization values influence polyphenols in soymilk manufactured from different genotypes, particularly black soybean has not been well characterized. This study's aims were to investigate how one- and two-phase ultrahigh temperature (UHT) processing technologies, with wide differences of lethality (F0 158.5 and 6.35, respectively), affected anti-prostate cancer DU145-cell properties of black soymilk compared to light-yellow-Proto soymilk. Phenolics were extracted from soymilk and used for chemical, cell cycle and apoptosis analyses. Total isoflavones and genistein in black soymilk were significantly higher than Proto soymilk by either processing methods. Compared to one-phase processing, two-phase produced higher gallic acid in both soybeans, and higher oxygen radical absorbance capacity (ORAC) in black soymilk. Soymilk processed from both genotypes by both UHT methods inhibited DU145 cells. Two-phase-UHT processed black soymilk was more effective than one-phase UHT-processed soymilk. IC50 values (mg/mL) of black and yellow soy extracts against prostate cancer cells differed only by 11%-25%, which were lower than the differences of total isoflavone (29%-33%) or genistein (>50% between two beans). The mechanism by which soymilk inhibited DU145 cell proliferation was through apoptosis as evidenced by cell cycle analyses and expressions of caspase-3, Bcl-2, and PARP-1 proteins. Antioxidant properties, isoflavones, and phenolic acids were negatively correlated with prostate-cancer-cell inhibition IC50 (p<0.05) with ORAC having the highest coefficient (r=-0.98). Overall, two-phase-UHT processing of soybean would produce soymilk products with a higher health benefit than a one-phase UHT method. PRACTICAL APPLICATION: This study characterized the potential prostate cancer prevention effect of soymilk's phenolic extract in black soybean and compared with yellow soybean. The crude extract can be prepared much less costly than purified isoflavones and has potential to be developed into a dietary supplement. This study shows differences of soymilks made by continuous high-temperature processing of two soybean types and can serve as a scientific foundation for future clinical research and commercialization.

Research Progress on Using Nanoparticles to Enhance the Efficacy of Drug Therapy for Chronic Mountain Sickness.

Chronic mountain sickness (CMS) poses a significant health risk to individuals who rapidly ascend to high altitudes, potentially endangering their lives. Nanoparticles (NPs) offer an effective means of transporting and delivering drugs, protecting nucleic acids from nuclease degradation, and mediating the expression of target genes in specific cells. These NPs are almost non-toxic and easy to prepare and store, possess a large surface area, exhibit good biocompatibility and degradability, and maintain good stability. They can be utilized in the treatment of CMS to enhance the therapeutic efficacy of drugs. This paper provides an overview of the impact of NPs on CMS, discussing their roles as nanocarriers and their potential in CMS treatment. It aims to present novel therapeutic strategies for the clinical management of CMS and summarizes the relevant pathways through which NPs contribute to plateau disease treatment, providing a theoretical foundation for future clinical research.

Strategies for Equitable Recruitment to Engage Underrepresented Youth and Their Families into Clinical Research: Findings from the BEAD-T1D Pilot Study

Plain Language SummaryPrevious studies have demonstrated a need for increased diverse representation in clinical trials. However, they have not considered the impact of equitable and culturally congruent recruitment practices on underrepresented and underserved families. This study presents recruitment/retention strategies to address disparities in clinical trial recruitment to increase representation and participation of underrepresented families. This study offers practical strategies to increase diverse representation in clinical trials to lay the foundation for equitable clinical research.

Identifying biomarkers for nasopharyngeal carcinoma diagnosis and chemoradiotherapy response using serum endogenous small molecules profiling

Changes in metabolic characteristics are important features of tumor progression and prognosis, including nasopharyngeal carcinoma (NPC). Identifying serum metabolites as potential diagnostic and chemoradiotherapy response biomarkers for NPC is therefore crucial. In this study, ultra-performance liquid chromatography coupled with linear ion trap quadrupole orbitrap high-resolution mass spectrometry (UPLC-LTQ-Orbitrap MS) was used to analyze metabolic variations among controls, NPC patients, and NPC patients undergoing chemoradiotherapy (CRT). Univariate and multivariate analyses revealed seven differential metabolites between the control and NPC groups and eleven metabolites between the CRT and NPC groups. Five common metabolites, gluconic acid, palmitic acid, LysoPC (15:0/0:0), stearic acid, and LysoPC (20:2(11Z,14Z)/0:0), were consistently altered across groups. Notably, the first four metabolites were adjusted closer to normal after chemoradiotherapy, while this change is not reflected at LysoPC (20:2(11Z,14Z)/0:0). These common metabolites were enriched in five pathways. These findings underscore the importance of serum metabolite profiling in NPC diagnosis and treatment response assessment and offer a promising foundation for further clinical research.

Evaluating Microsoft Bing with ChatGPT-4 for the assessment of abdominal computed tomography and magnetic resonance images.

To evaluate the performance of Microsoft Bing with ChatGPT-4 technology in analyzing abdominal computed tomography (CT) and magnetic resonance images (MRI). A comparative and descriptive analysis was conducted using the institutional picture archiving and communication systems. A total of 80 abdominal images (44 CT, 36 MRI) that showed various entities affecting the abdominal structures were included. Microsoft Bing's interpretations were compared with the impressions of radiologists in terms of recognition of the imaging modality, identification of the imaging planes (axial, coronal, and sagittal), sequences (in the case of MRI), contrast media administration, correct identification of the anatomical region depicted in the image, and detection of abnormalities. Microsoft Bing detected that the images were CT scans with 95.4% accuracy (42/44) and that the images were MRI scans with 86.1% accuracy (31/36). However, it failed to detect one CT image (2.3%) and misidentified another CT image as an MRI (2.3%). On the other hand, it also misidentified four MRI as CT images (11.1%) and one as an X-ray (2.7%). Bing achieved an 83.75% success rate in correctly identifying abdominal regions, with 90% accuracy for CT scans (40/44) and 77.7% for MRI scans (28/36). Concerning the identification of imaging planes, Bing achieved a success rate of 95.4% for CT images and 83.3% for MRI. Regarding the identification of MRI sequences (T1-weighted and T2-weighted), the success rate was 68.75%. In the identification of the use of contrast media for CT scans, the success rate was 64.2%. Bing detected abnormalities in 35% of the images but achieved a correct interpretation rate of 10.7% for the definite diagnosis. While Microsoft Bing, leveraging ChatGPT-4 technology, demonstrates proficiency in basic task identification on abdominal CT and MRI, its inability to reliably interpret abnormalities highlights the need for continued refinement to enhance its clinical applicability. The contribution of large language models (LLMs) to the diagnostic process in radiology is still being explored. However, with a comprehensive understanding of their capabilities and limitations, LLMs can significantly support radiologists during diagnosis and improve the overall efficiency of abdominal radiology practices. Acknowledging the limitations of current studies related to ChatGPT in this field, our work provides a foundation for future clinical research, paving the way for more integrated and effective diagnostic tools.

Butyrate protects the intestinal barrier by upregulating Fut2 expression via MEK4-JNK signaling pathway activation.

Necrotizing enterocolitis (NEC) is a severe gastrointestinal inflammatory disease in neonates. Fucosyltransferase 2 (Fut2) regulates intestinal epithelial cell fucosylation. In this study, we aimed to investigate butyrate-mediated upregulation of Fut2 expression and the underlying mechanisms. In vivo and in vitro models were established. SP600125 was used to inhibit the MEK4-JNK pathway, and anisomycin was used to activate the MEK4-JNK pathway. Fut2, occludin, and ZO-1 expressions were assessed. Furthermore, intestinal permeability was analyzed by FITC-Dextran. The expression of proteins in the MEK-4-JNK pathway was examined by western blotting. In vivo, the addition of exogenous butyrate notably upregulated Fut2, occludin, and ZO-1 expressions and reduced intestinal permeability in mice with NEC. Butyrate may increase the phosphorylation of MEK4, JNK, and c-jun, which are key components of the MEK4-JNK pathway. Additionally, SP600125 inhibited their phosphorylation, which was reversed by anisomycin treatment. In vitro, butyrate substantially increased occludin and ZO-1 expressions. Butyrate considerably increased Fut2 expression and markedly upregulated p-MEK4, p-JNK, and p-c-jun expressions. SP600125 administration decreased their expressions, while anisomycin administration increased their expressions. Butyrate upregulated Fut2 expression via activation of the MEK4-JNK pathway, improved intestinal barrier integrity, and protected neonatal mice from NEC. We found that exogenous butyrate could improve intestinal barrier integrity and protect against NEC in neonatal mice. Our data showed that exogenous butyrate supplementation upregulated Fut2 expression by activating the MEK4-JNK pathway. Our study provides novel insights into the pathogenesis of NEC, thereby laying an experimental foundation for future clinical research on the use of butyrate in NEC treatment.

In silico analysis of potential inhibitors for breast cancer targeting 17beta-hydroxysteroid dehydrogenase type 1 (17beta-HSD1) catalyses.

Breast cancer (BC) is still one of the major issues in world health, especially for women, which necessitates innovative therapeutic strategies. In this study, we investigated the efficacy of retinoic acid derivatives as inhibitors of 17beta-hydroxysteroid dehydrogenase type 1 (17beta-HSD1), which plays a crucial role in the biosynthesis and metabolism of oestrogen and thereby influences the progression of BC and, the main objective of this investigation is to identify the possible drug candidate against BC through computational drug design approach including PASS prediction, molecular docking, ADMET profiling, molecular dynamics simulations (MD) and density functional theory (DFT) calculations. The result has reported that total eight derivatives with high binding affinity and promising pharmacokinetic properties among 115 derivatives. In particular, ligands 04 and 07 exhibited a higher binding affinity with values of -9.9 kcal/mol and -9.1 kcal/mol, respectively, than the standard drug epirubicin hydrochloride, which had a binding affinity of -8.2 kcal/mol. The stability of the ligand-protein complexes was further confirmed by MD simulations over a 100-ns trajectory, which included assessments of hydrogen bonds, root mean square deviation (RMSD), root mean square Fluctuation (RMSF), dynamic cross-correlation matric (DCCM) and principal component analysis. The study emphasizes the need for experimental validation to confirm the therapeutic utility of these compounds. This study enhances the computational search for new BC drugs and establishes a solid foundation for subsequent experimental and clinical research.

Comprehensive profiling of the chemical constituents in Dayuanyin decoction using UPLC-QTOF-MS combined with molecular networking

Context Dayuanyin decoction is a traditional Chinese medicine formulation that is commonly used in modern clinical practice to treat viral infections such as viral pneumonia, viral fever, influenza, and hepatitis. Although the usage rate of Dayuanyin decoction is gradually increasing in clinical practice, its pharmacological constituents are still unclear. Objective This study comprehensively characterized the chemical constituents in Dayuanyin decoction using ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS) and molecular networking. Materials and methods The overall strategy involved retrieving structural information, such as fragment ions and precursor ion masses, from self-built databases to identify the target constituents of the Dayuanyin decoction extract. The identification of non-targeted constituents was achieved by analyzing different categories, fragment pathways, mass spectrometry data, and the relationships between clusters of structures in molecular networking. Unannotated constituents were inferred from secondary mass spectrometry similarity and molecular weight differences and annotated constituents in the same constituent cluster. A few predicted constituents were selected and validated by comparing them to reference standards under identical mass spectrometry conditions. Results This study preliminarily identified 216 constituents, including flavonoids, amino acids, alkaloids, triterpenes, steroidal saponins, phenylpropanoids, and other constituents. Conclusions This integrated strategy using UPLC-QTOF-MS and molecular networking lays the foundation for clinical research on pharmacologically active substances in Dayuanyin decoction and could be popularized for the comprehensive profiling of chemical constituents of other traditional Chinese medicines.

Insilico and Invitro approach to assessing the antimicrobial efficiency of novel AMP variants derived from Lactobacillus sp. against ESKAPE pathogens

Antimicrobial resistance is a major threat worldwide especially when it comes to nosocomial infections caused by ESKAPE bacteria. These pathogens exhibit a remarkable capacity to develop resistance to antimicrobial treatments. Probiotics are receiving considerable attention as potential antimicrobial therapies that are safe, and very effective. The objective of this study is to identify a possible treatment using antimicrobial peptides (AMPs) derived from probiotics. The primary objective is to comprehend the interplay between AMPs and the virulence proteins produced by ESKAPE pathogens that are linked with biofilms. We subjected the 12 peptides found in our earlier investigation to a comprehensive screening approach targeting the virulence proteins of ESKAPE infections by applying shape complementarity concepts and chose the docked complexes with the lowest energy score. The screening process involved assessing binding affinity and interactions with active residues using sophisticated computational tools such as HPEPDOCK, ClusPro 2.0, and AutoDock Vina. The AMP designated as plsa_07 was selected for subsequent examination and validated using molecular dynamic simulations. The in vitro assay demonstrated the antibacterial and antibiofilm properties of AMP plsa_07, with a minimal inhibitory concentration ranging from 1 to 4 μg/ml. The AMP plsa_07 demonstrated biofilm inhibition and eradication action against various bacteria, including E.faecium, S.aureus, K.pneumoniae, A.baumannii, and P.aeruginosa, with a range of effectiveness between 17% and 70%. This study establishes a fundamental foundation for clinical research on the possible application of therapeutic peptides produced from probiotics to address the increasing problem of drug-resistant infections.

Exploring Acori Tatarinowii Rhizoma and Polygalae Radix in Alzheimer's: Network pharmacology and molecular docking analysis.

Explore Acori Tatarinowii Rhizoma (ATR) and Polygalae Radix (PR) mechanisms in Alzheimer's disease (AD) treatment through network pharmacology. ATR-PR was investigated in the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database, Batman, and Traditional Chinese Medicines Integrated Database (TCMID) to gather information on its chemical components and target proteins. Target genes associated with AD were retrieved from the GeneCards and National Center for Biotechnology Information (NCBI) databases. The integration of these datasets with potential targets facilitated the construction of an AD and ATR-PR protein-protein interaction (PPI) network using the STRING database. The resulting network identified the core active ingredients and main targets of ATR-PR in AD treatment. Cluster analysis of the PPI network was performed using Cytoscape 3.7.1. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted using the Metascape database. Molecular docking simulations revealed potential interactions between the main active ingredients and core targets. Our analysis identified 8 putative components and 455 targets of ATR-PR. We systematically searched for 1306 genes associated with AD, conducted Venn diagram analysis resulting in 156 common targets, and constructed a PPI network with 57 key targets. GO functional analysis highlighted the primary biological processes associated with oxidative stress. KEGG pathway enrichment analysis revealed the involvement of 64 signaling pathways, with the PI3K/Akt signaling pathway playing a key role. Molecular docking analysis indicated a high affinity between the potential targets of ATR-PR and the main compounds of AD. This study sheds light on the complex network of interactions involving ATR-PR in the context of AD. The identified targets, pathways, and interactions provide a foundation for understanding the potential therapeutic mechanisms. The involvement of oxidative stress-related processes and the crucial role of the PI3K/Akt signaling pathway suggest avenues for targeted therapeutic interventions in Alzheimer's disease treatment. Our proposition of the combined use of ATR-PR has emerged as a potential treatment strategy for AD, supported by a network pharmacology approach. This framework provides a robust foundation for future clinical applications and experimental research in the pursuit of effective Alzheimer's disease treatments.

Integrated Network Pharmacology Analysis and Experimental Validation to Elucidate the Mechanism of Acteoside in Treating Diabetic Kidney Disease.

Acteoside, an active ingredient found in various medicinal herbs, is effective in the treatment of diabetic kidney disease (DKD); however, the intrinsic pharmacological mechanism of action of acteoside in the treatment of DKD remains unclear. This study utilizes a combined approach of network pharmacology and experimental validation to investigate the potential molecular mechanism systematically. First, acteoside potential targets and DKD-associated targets were aggregated from public databases. Subsequently, utilizing protein-protein interaction (PPI) networks, alongside GO and KEGG pathway enrichment analyses, we established target-pathway networks to identify core potential therapeutic targets and pathways. Further, molecular docking facilitated the confirmation of interactions between acteoside and central targets. Finally, the conjectured molecular mechanisms of acteoside against DKD were verified through experimentation on unilateral nephrectomy combined with streptozotocin (STZ) rat model. The underlying downstream mechanisms were further investigated. Network pharmacology identified 129 potential intersected targets of acteoside for DKD treatment, including targets such as AKT1, TNF, Casp3, MMP9, SRC, IGF1, EGFR, HRAS, CASP8, and MAPK8. Enrichment analyses indicated the PI3K-Akt, MAPK, Metabolic, and Relaxin signaling pathways could be involved in this therapeutic context. Molecular docking revealed high-affinity binding of acteoside to PIK3R1, AKT1, and NF-κB1. In vivo studies validated the therapeutic efficacy of acteoside, demonstrating reduced blood glucose levels, improved serum Scr and BUN levels, decreased 24-hour urinary total protein (P<0.05), alongside mitigated podocyte injury (P<0.05) and ameliorated renal pathological lesions. Furthermore, this finding indicates that acteoside inhibits the expression of pyroptosis markers NLRP3, Caspase-1, IL-1β, and IL-18 through the modulation of the PI3K/AKT/NF-κB pathway. Acteoside demonstrates renoprotective effects in DKD by regulating the PI3K/AKT/NF-κB signaling pathway and alleviating pyroptosis. This study explores the pharmacological mechanism underlying acteoside's efficacy in DKD treatment, providing a foundation for further basic and clinical research.

Research Advancements on the Correlation Between Spontaneous Intracerebral Hemorrhage of Different Etiologies and Imaging Markers of Cerebral Small Vessel Disease.

The purpose of this review is to identify the correlation between ICH and CSVD imaging markers under SMASH-U classification by searching and analyzing a large number of literatures in recent years, laying a theoretical foundation for future clinical research. At the same time, by collecting clinical data to evaluate patient prognosis, analyzing whether there are differences or supplements between clinical trial conclusions and previous theories, and ultimately guiding clinical diagnosis and treatment through the analysis of imaging biomarkers. In this review, by searching CNKI, Web of Science, PubMed, FMRS and other databases, the use of "spontaneous intracerebral hemorrhage", "hypertensive hemorrhagic cerebral small vessel disease", "cerebral small vessel disease imaging", "Based cerebral small vessel diseases", "SMASH the -u classification" and their Chinese equivalents for the main search term. We focused on reading and analyzing hundreds of relevant literatures in the last decade from August 2011 to April 2020, and also included some earlier literatures with conceptual data sources. After screening and ranking the degree of relevance to this study, sixty of them were cited for analysis and elaboration. In patients with ICH, the number of cerebral microbleeds in lobes, basal ganglia, and the deep brain is positively correlated with ICH volume and independently correlated with neurological functional outcomes; white matter hyperintensity severity is positively correlated with ICH recurrence risk; multiple lacunar infarction independently predict the risk of ICH; severe brain atrophy is an independent risk factor for a poor prognosis in the long term in patients diagnosed with ICH; and the number of enlarged perivascular spaces is correlated with ICH recurrence. However, small subcortical infarct and ICH are the subject of few studies. Higher CSVD scores are independently associated with functional outcomes at 90 days in patients diagnosed with ICH.

STAT3 ACTIVATION IN THE SYNOVIAL TISSUES FROM THE HIP JOINT IN THE EARLY STAGE OF RAPIDLY DESTRUCTIVE COXOPATHY

The interleukin-6/gp130-associated Janus Kinases/STAT3 axis is known to play an important role in mediating inflammatory signals, resulting in production of matrix metalloproteinase-3 (MMP-3). The hip joints with rapidly destructive coxopathy (RDC) demonstrate rapid chondrolysis, probably by increased production of MMP-3 observed in the early stage of RDC. In the recent study, no apparent activation of STAT3 has been shown in the synovial tissues obtained from the osteoarthritic joint at operation. However, no data are currently available on STAT3 activation in the synovial tissues in the early stage of RDC. This study aimed to elucidate STAT3 activation in the synovial tissues in the early stage of RDC. Synovial tissues within 7 months from the disease onset were obtained from four RDC patients with femoral head destruction and high serum levels of MMP-3. RDC synovial tissues showed the synovial lining hyperplasia with an increase of CD68-positive macrophages and CD3-positive T lymphocytes. STAT3 phosphorylation was found in the synovial tissues by immunohistochemistry using anti-phospho-STAT3 antibody. The majority of phospho-STAT3-positive cells were the synovial lining cells and exhibited negative expression of macrophage or T cell marker. Treatment with tofacitinib, a Janus Kinase inhibitor, resulted in a decrease in phospho-STAT3-positive cells, especially with high intensity, indicating effective suppression of STAT3 activation in RDC synovial tissues. Inhibitory effect of tofacitinib could act through the Janus Kinase/STAT3 axis in the synovial tissues in the early stage of RDC. Therefore, STAT3 may be a potential therapeutic target for prevention of joint structural damage in RDC.Acknowledgements: This study was supported by Katakami Foundation for Clinical Research.

Traditional Chinese medicine treatment for benign thyroid nodules: Literature review.

Thyroid nodules (TNs) are pathological changes characterized by abnormal proliferation of thyroid gland tissue. Approximately 19% to 67% of asymptomatic individuals are diagnosed with TNs, with the majority being benign nodules and 4% to 6.5% being thyroid cancer nodules. Western medicine recommends regular examinations and surgery, while traditional Chinese medicine (TCM) provides an alternative choice to maintain thyroid function and reduce the need for surgery. However, in Taiwan, research on TCM treatment for benign TNs is primarily limited to case reports, lacking large-scale and systematic clinical studies. We conducted a search of electronic databases including PubMed, Google Scholar, Wanfang Data, and China National Knowledge Infrastructure to collect clinical trials related to TCM treatment for TNs. Our goal is to provide new treatment options, further validate the value of TCM in the treatment of TNs, and lay a foundation for future clinical research.

The andrographolide derivative, AND7, and TRAIL combination attenuates acute lymphoblastic leukemia through P53-regulated ROS accumulation

Acute lymphoblastic leukemia (ALL) is a malignant disease of the hematologic system. The current treatment is based on chemotherapeutic drugs, which are becoming less effective due to drug resistance. TNF-related apoptosis-inducing ligand (TRAIL) is an apoptotic protein used to treat cancer that does not affect healthy cells. In recent years, however, ALL cells (e.g., U937) have become more resistant to TRAIL. A novel andrographolide derivative (AND7) with high efficiency and low toxicity was synthesized and combined with TRAIL after the optimal combination ratio was screened using U937 cells. We used peripheral blood mononuclear cells (PBMCs) from patients before the initial treatment of ALL as a model and PBMCs from healthy subjects as a control to determine the mechanism underlying ALL treatment. AND7/TRAIL combination treatment was shown to prevent the original TRAIL-resistant cells from activating the caspase-8/caspase-3 pathway through DR4/DR5 and promote apoptosis via expression of ROS and the apoptotic gene, P53, to achieve an anti-cancer effect. Notably, this study demonstrated that the AND7/TRAIL combination enhanced the anti-cancer effect of AND7 and improved TRAIL resistance. Therefore, the AND7/TRAIL combination is promising for treating ALL and lays the foundation for clinical research.

Exploring the efficacy of laser speckle contrast imaging in the stratified diagnosis of rosacea: a quantitative analysis of facial blood flow dynamics across varied regions.

Rosacea has a high incidence, significantly impacts quality of life, and lacks sufficient diagnostic techniques. This study aimed to investigate the feasibility of laser speckle contrast imaging (LSCI) for measuring facial blood perfusion in patients with rosacea and to identify differences in blood flow among various facial regions associated with different rosacea subtypes. From June to December 2023, 45 patients were recruited, with 9 excluded, leaving 36 subjects: 12 with erythematotelangiectatic rosacea (ETR), 12 with papulopustular rosacea (PPR), and 12 healthy controls. The Think View multispectral imaging analyzer assessed inflammation via gray reading values across the full face and five facial areas: forehead, nose, cheeks, and chin. LSCI measured and analyzed blood perfusion in the same areas. Plasma biomarkers interleukin-6 (IL-6), IL-1β, and tumor necrosis factor-α (TNF-α) were tested in different groups. Both ETR and PPR groups showed increased average blood perfusion and facial inflammation intensity by gray values compared to controls, with statistically significant differences. Average blood perfusion of ETR and PPR groups showed increased values in the forehead, cheeks, and nose, compared to controls, and the values in the cheeks were statistically different between ETR and PPR. The facial inflammation intensity of the ETR group showed increased values in the forehead and cheeks, and the PPR group showed increased gray values in the forehead, cheeks, nose, and chin compared to controls, and the values for the cheeks, nose, and chin were statistically significantly different between ETR and PPR. Plasma biomarkers IL-6, IL-1β, and TNF-α were significantly elevated in both ETR and PPR groups compared to controls. LSCI is a valuable, non-invasive tool for assessing blood flow dynamics in rosacea, providing a data foundation for clinical research. Different rosacea subtypes exhibit distinct lesion distribution and blood flow patterns, and both ETR and PPR could affect all facial areas, particularly the cheeks in ETR and the forehead, nose, and chin in PPR.

Perampanel attenuates oxidative stress and pyroptosis following subarachnoid hemorrhage via the SIRT3/FOXO3α pathway

Subarachnoid hemorrhage (SAH) occurs most commonly after rupture of an aneurysm, resulting in high disability and mortality due to the absence of effective therapy. Its subsequent stage, early brain injury (EBI), promotes the sustainable development of injury in the brain and ultimately leads to poor prognosis. As a new antiepileptic drug, the effect of perampanel on EBI after SAH is unknown. Pyroptosis, a process of inflammatory programmed cell death, has been confirmed in most studies to play a substantial role in aggravating SAH-post EBI. Similarly, oxidative stress is closely involved in neuronal pyroptosis and the pathophysiological mechanism of SAH-post EBI, leading to a devastating outcome for SAH patients. Nonetheless, no studies have been conducted to determine whether perampanel reduces pyroptosis and oxidative stress in the context of SAH-induced EBI. Rat SAH model via endovascular perforation was constructed in this study, to assess the neuroprotective effect of perampanel on SAH-post EBI, and to clarify the possible molecular mechanism. By means of the neurological score, brain edema detection, FJB staining, immunofluorescence, WB, ELISA, and ROS assay, we found that perampanel can improve neuroscores and reduce brain edema and neuronal degeneration at 24 h after SAH; we also found that perampanel reduced oxidative stress, neuronal pyroptosis, and inhibition of the SIRT3-FOXO3α pathway at 24 h after SAH. When 3-TYP, an inhibitor of SIRT3, was administered, the effects of perampanel on the SIRT3-FOXO3a pathway, antioxidant stress, and neuronal pyroptosis were reversed. Taken together, our data indicate that perampanel attenuates oxidative stress and pyroptosis following subarachnoid hemorrhage via the SIRT3/FOXO3α pathway. This study highlights the application value of perampanel in subarachnoid hemorrhage and lays a foundation for clinical research and later transformation of perampanel in SAH.

Big Data Education for Clinical Documentation

Nursing educators and students need new competencies and tools for creating and analyzing clinical documentation and big data to maximize value-based reimbursements and data sharing.&amp;nbsp; Carefully structured and shareable documentation of nursing diagnoses, goals, interventions and outcomes, available in the EHR (electronic health record), may be aggregated and analyzed to provide a foundation for population health, quality improvement and clinical research.&amp;nbsp; One way to access anonymized clinical data for use in academic and clinical data sharing is via Project NeLL™ (Nurses electronic Learning Laboratory™), an innovative suite of online applications for teaching and practicing nursing data science from the Nell Woodruff Hodgson School of Nursing of Emory University's Center for Data Science.&amp;nbsp; Emory is collaborating with Rutgers University School of Nursing to teach graduate students using Project NeLL.

Ferroptosis mechanism and Alzheimer's disease.

Regulated cell death is a genetically determined form of programmed cell death that commonly occurs during the development of living organisms. This process plays a crucial role in modulating homeostasis and is evolutionarily conserved across a diverse range of living organisms. Ferroptosis is a classic regulatory mode of cell death. Extensive studies of regulatory cell death in Alzheimer's disease have yielded increasing evidence that ferroptosis is closely related to the occurrence, development, and prognosis of Alzheimer's disease. This review summarizes the molecular mechanisms of ferroptosis and recent research advances in the role of ferroptosis in Alzheimer's disease. Our findings are expected to serve as a theoretical and experimental foundation for clinical research and targeted therapy for Alzheimer's disease.