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Journal of Cancer 2024Although fangchinoline has been widely used as an adjunct therapy for a variety of inflammatory and cancerous diseases, its mechanism of action on tumor cells remains...
Although fangchinoline has been widely used as an adjunct therapy for a variety of inflammatory and cancerous diseases, its mechanism of action on tumor cells remains unclear. Fangchinoline derivative LYY-35 reduced the number of A549 cells, deformed cell morphology and increased cell debris. Cell viability was significantly reduced, while the same concentration of LYY-35 had little effect on BEAS-2B viability of normal lung epithelial cells. In addition, LYY-35 can also reduce the migration, proliferation and invasion ability of A549 cells. Levels of β-catenin, ZO-1 and ZEB-1 proteins, biomarkers of cell adhesion and epithelial mesenchymal transformation, were significantly reduced. The levels of superoxide dismutase and lactate dehydrogenase decreased gradually, while the levels of glutathione, malondialdehyde and intracellular and extracellular ROS increased significantly. At the same time, LYY-35 induced increased apoptosis, increased expression of Bax, cleaved caspase3, cleaved PARP1, and decreased expression of Bcl-xl, which blocked the cell cycle to G0/G1 phase. The expressions of cell cycle checkpoint proteins Cyclin B1, Cyclin E1, CDK6, PCNA and PICH were significantly decreased. With the increase of LYY-35 concentration, the trailing phenomenon was more obvious in single cell gel electrophoresis. DNA damage repair proteins: BLM, BRCA-1 and PARP-1 expression decreased gradually.LYY-35 can inhibit the proliferation of non-small cell lung cancer A549 cells, block cell cycle, promote apoptosis, increase ROS production, cause DNA damage and interfere with DNA replication. LYY-35 is promising for the treatment of non-small cell lung cancer in the future.
PubMed: 38947387
DOI: 10.7150/jca.96582 -
Frontiers in Public Health 2024This study aimed to determine the risk factors associated with fluctuations in nucleic acid CT values in patients infected with the Omicron variant during an outbreak at...
OBJECTIVE
This study aimed to determine the risk factors associated with fluctuations in nucleic acid CT values in patients infected with the Omicron variant during an outbreak at a hospital in Changchun city.
METHODS
A retrospective analysis was conducted on general information, medical history, vaccination history, and laboratory test data of COVID-19 patients infected with the Omicron variant and admitted to the hospital in Changchun from March 2022 to April 2022. The study aimed to explore the factors influencing nucleic acid CT value fluctuations in COVID-19 patients infected with the Omicron variant in Changchun city.
RESULTS
Fluctuations in nucleic acid CT values were significantly correlated with occupation composition ( = 0.030), hospital stay duration ( = 0.000), heart rate ( = 0.026), creatinine ( = 0.011), platelet count ( = 0.000), glutamic-pyruvic transaminase ( = 0.045), and glutamic oxaloacetic transaminase ( = 0.017). Binary logistic regression analysis revealed significant correlations between hospital stay duration ( = 0.000), platelet count ( = 0.019), heart rate ( = 0.036), and nucleic acid CT value fluctuations ( < 0.05), indicating that they were independent risk factors. Red blood cell count was identified as a factor influencing nucleic acid CT value fluctuations in Group A patients. Occupation composition, direct bilirubin, and platelet count were identified as factors influencing nucleic acid CT value fluctuations in Group B patients. Further binary logistic regression analysis indicated that occupational composition and direct bilirubin are significant independent factors for nucleic acid CT value fluctuations in Group B patients, positively correlated with occupational risk and negatively correlated with direct bilirubin.
CONCLUSION
Therefore, enhancing patients' immunity, increasing physical exercise to improve myocardial oxygen consumption, reducing the length of hospital stays, and closely monitoring liver function at the onset of hospitalization to prevent liver function abnormalities are effective measures to control fluctuations in nucleic acid CT values.
PubMed: 38947348
DOI: 10.3389/fpubh.2024.1377135 -
World Journal of Gastroenterology Jun 2024Coronavirus disease 2019 (COVID-19), caused by the highly pathogenic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), primarily impacts the respiratory... (Review)
Review
Coronavirus disease 2019 (COVID-19), caused by the highly pathogenic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), primarily impacts the respiratory tract and can lead to severe outcomes such as acute respiratory distress syndrome, multiple organ failure, and death. Despite extensive studies on the pathogenicity of SARS-CoV-2, its impact on the hepatobiliary system remains unclear. While liver injury is commonly indicated by reduced albumin and elevated bilirubin and transaminase levels, the exact source of this damage is not fully understood. Proposed mechanisms for injury include direct cytotoxicity, collateral damage from inflammation, drug-induced liver injury, and ischemia/hypoxia. However, evidence often relies on blood tests with liver enzyme abnormalities. In this comprehensive review, we focused solely on the different histopathological manifestations of liver injury in COVID-19 patients, drawing from liver biopsies, complete autopsies, and liver analyses. We present evidence of the direct impact of SARS-CoV-2 on the liver, substantiated by observations of viral entry mechanisms and the actual presence of viral particles in liver samples resulting in a variety of cellular changes, including mitochondrial swelling, endoplasmic reticulum dilatation, and hepatocyte apoptosis. Additionally, we describe the diverse liver pathology observed during COVID-19 infection, encompassing necrosis, steatosis, cholestasis, and lobular inflammation. We also discuss the emergence of long-term complications, notably COVID-19-related secondary sclerosing cholangitis. Recognizing the histopathological liver changes occurring during COVID-19 infection is pivotal for improving patient recovery and guiding decision-making.
PubMed: 38947288
DOI: 10.3748/wjg.v30.i22.2866 -
Proceedings of the ... IEEE/RSJ... Oct 2023Bronchoscopy is currently the least invasive method for definitively diagnosing lung cancer, which kills more people in the United States than any other form of cancer....
Bronchoscopy is currently the least invasive method for definitively diagnosing lung cancer, which kills more people in the United States than any other form of cancer. Successfully diagnosing suspicious lung nodules requires accurate localization of the bronchoscope relative to a planned biopsy site in the airways. This task is challenging because the lung deforms intraoperatively due to respiratory motion, the airways lack photometric features, and the anatomy's appearance is repetitive. In this paper, we introduce a real-time camera-based method for accurately localizing a bronchoscope with respect to a planned needle insertion pose. Our approach uses deep learning and accounts for deformations and overcomes limitations of global pose estimation by estimating pose relative to anatomical landmarks. Specifically, our learned model considers airway bifurcations along the airway wall as landmarks because they are distinct geometric features that do not vary significantly with respiratory motion. We evaluate our method in a simulated dataset of lungs undergoing respiratory motion. The results show that our method generalizes across patients and localizes the bronchoscope with accuracy sufficient to access the smallest clinically-relevant nodules across all levels of respiratory deformation, even in challenging distal airways. Our method could enable physicians to perform more accurate biopsies and serve as a key building block toward accurate autonomous robotic bronchoscopy.
PubMed: 38947248
DOI: 10.1109/iros55552.2023.10342115 -
Frontiers in Cardiovascular Medicine 2024Anthracyclines are effective in treating acute myeloid leukemia (AML) but limited by cardiotoxicity. CPX-351, a liposomal daunorubicin and cytarabine, may provide...
INTRODUCTION
Anthracyclines are effective in treating acute myeloid leukemia (AML) but limited by cardiotoxicity. CPX-351, a liposomal daunorubicin and cytarabine, may provide therapeutic benefit with less cardiotoxicity. Acute changes in left ventricular systolic function and cardiac biomarkers were evaluated after a cycle of CPX-351 in children with relapsed AML treated on the phase 1/2 Children's Oncology Group study, AAML1421.
METHODS
Subjects received 135 units/m/dose of CPX-351 on days 1, 3, and 5 as cycle 1. Echocardiograms were performed and centrally quantitated at baseline and at the end of cycle 1 (day 29 +/- 1 week). High sensitivity troponin (hs-cTnT) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) were measured at baseline and serially through the end of cycle 1 (days 5, 8, 15, 22 and 29). Differences between baseline and post-CPX-351 echo/biomarker measures were analyzed using Wilcoxon signed rank tests. Linear regression was used to model post-CPX-351 left ventricular ejection fraction (LVEF) with cTnT/NT-proBNP at each time point, controlling for baseline LVEF. Cancer therapy related cardiac dysfunction (CTRCD) was defined as a decline in LVEF of ≥10%-<50%.
RESULTS
Twenty-five of 38 heavily anthracycline pre-treated (median 348 mg/m daunorubicin equivalents) subjects enrolled on AAML1421 were included in the cardiac analyses. At baseline, centrally quantitated LVEF was <50% in 8 of 25 subjects (32%) with a median LVEF of 53.8% [48.0, 56.9]. Following CPX-351, LVEF declined significantly (ΔLVEF -3.3% [-7.8, 0]) and 6 of 25 subjects (24%) experienced CTRCD. Amongst all subjects, hs-cTnT was modestly increased at end of cycle 1 compared to baseline [baseline hs-cTnT 7.2 (3, 10.6); ΔcTnT 1.80 (0, 6.1), = 0.03]. NT-proBNP remained stably elevated without significant change. No significant associations were seen between NT-proBNP or cTnT levels and post-CPX-351 LVEF.
DISCUSSION
In this single arm study of anthracycline pre-treated children exposed to CPX-351, baseline abnormalities in cardiovascular function were prevalent. Following CPX-351, LVEF decreased, cTnT increased, and NT-proBNP did not change. Longer follow-up is needed to determine whether these changes result in clinically meaningful long-term decrements in cardiac function. An ongoing randomized trial of CPX-351 compared to standard anthracyclines in anthracycline naïve patients will provide further insight into the cardiac effects of CPX-351 (ClinicalTrials.gov; NCT04293562).
PubMed: 38947228
DOI: 10.3389/fcvm.2024.1347547 -
Cureus Jun 2024Metabolic syndrome (MetS) encompasses a cluster of metabolic abnormalities, including insulin resistance, hypertension, abdominal obesity, and dyslipidemia, increasing... (Review)
Review
Metabolic syndrome (MetS) encompasses a cluster of metabolic abnormalities, including insulin resistance, hypertension, abdominal obesity, and dyslipidemia, increasing cardiovascular disease and type 2 diabetes risks. Cellulite, a cosmetic condition marked by dimpled skin, predominantly affects women and shares risk factors with MetS, such as obesity and hormonal imbalances. This review examines the potential link between MetS and cellulite, focusing on shared pathophysiological pathways and implications for clinical practice and future research. Common factors such as inflammation, hormonal changes, and adipose tissue dysfunction are explored. The review highlights the importance of longitudinal studies to track cellulite progression in MetS patients, biomarker identification for early detection, intervention trials to assess therapeutic efficacy, mechanistic studies to elucidate underlying pathways and the impact of comorbidities on cellulite development. Understanding these relationships can enhance prevention, diagnosis, and treatment strategies for both MetS and cellulite, addressing significant public health and cosmetic concerns.
PubMed: 38947139
DOI: 10.7759/cureus.63464 -
Frontiers in Cellular and Infection... 2024In infants with cholestasis, variations in the enterohepatic circulation of bile acids and the gut microbiota (GM) characteristics differ between those with biliary...
INTRODUCTION
In infants with cholestasis, variations in the enterohepatic circulation of bile acids and the gut microbiota (GM) characteristics differ between those with biliary atresia (BA) and non-BA, prompting a differential analysis of their respective GM profiles.
METHODS
Using 16S rDNA gene sequencing to analyse the variance in GM composition among three groups: infants with BA (BA group, n=26), non-BA cholestasis (IC group, n=37), and healthy infants (control group, n=50). Additionally, correlation analysis was conducted between GM and liver function-related indicators.
RESULTS
Principal component analysis using Bray-Curtis distance measurement revealed a significant distinction between microbial samples in the IC group compared to the two other groups. IC-accumulated co-abundance groups exhibited positive correlations with aspartate aminotransferase, alanine aminotransferase, total bilirubin, direct bilirubin, and total bile acid serum levels. These correlations were notably reinforced upon the exclusion of microbial samples from children with BA.
CONCLUSION
The varying "enterohepatic circulation" status of bile acids in children with BA and non-BA cholestasis contributes to distinct GM structures and functions. This divergence underscores the potential for targeted GM interventions tailored to the specific aetiologies of cholestasis.
Topics: Humans; Biliary Atresia; Gastrointestinal Microbiome; Cholestasis; Infant; Bile Acids and Salts; Male; Female; RNA, Ribosomal, 16S; Bilirubin; Bacteria; DNA, Ribosomal; Feces
PubMed: 38947125
DOI: 10.3389/fcimb.2024.1402329 -
The Yale Journal of Biology and Medicine Jun 2024Joint hypermobility syndromes, particularly chronic pain associated with this condition, including Hypermobile Ehlers-Danlos Syndrome (hEDS) and Hypermobility Spectrum... (Review)
Review
Chronic Pain and Joint Hypermobility: A Brief Diagnostic Review for Clinicians and the Potential Application of Infrared Thermography in Screening Hypermobile Inflamed Joints.
Joint hypermobility syndromes, particularly chronic pain associated with this condition, including Hypermobile Ehlers-Danlos Syndrome (hEDS) and Hypermobility Spectrum Disorders (HSD), present diagnostic challenges due to their multifactorial origins and remain poorly understood from biomechanical and genomic-molecular perspectives. Recent diagnostic guidelines have differentiated hEDS, HSD, and benign joint hypermobility, providing a more objective diagnostic framework. However, incorrect diagnoses and underdiagnoses persist, leading to prolonged journeys for affected individuals. Musculoskeletal manifestations, chronic pain, dysautonomia, and gastrointestinal symptoms illustrate the multifactorial impact of these conditions, affecting both the physical and emotional well-being of affected individuals. Infrared thermography (IRT) emerges as a promising tool for joint assessment, especially in detecting inflammatory processes. Thermal distribution patterns offer valuable insights into joint dysfunctions, although the direct correlation between pain and inflammation remains challenging. The prevalence of neuropathies among hypermobile individuals accentuates the discordance between pain perception and thermographic findings, further complicating diagnosis and management. Despite its potential, the clinical integration of IRT faces challenges, with conflicting evidence hindering its adoption. However, studies demonstrate objective temperature disparities between healthy and diseased joints, especially under dynamic thermography, suggesting its potential utility in clinical practice. Future research focused on refining diagnostic criteria and elucidating the underlying mechanisms of hypermobility syndromes will be essential to improve diagnostic accuracy and enhance patient care in this complex and multidimensional context.
Topics: Humans; Thermography; Joint Instability; Chronic Pain; Ehlers-Danlos Syndrome; Inflammation; Infrared Rays
PubMed: 38947102
DOI: 10.59249/WGRS1619 -
Research Square Jun 2024Developmental anomalies of the hearing organ, the cochlea, are diagnosed in approximately one-fourth of individuals with congenital deafness. Most patients with cochlear...
Developmental anomalies of the hearing organ, the cochlea, are diagnosed in approximately one-fourth of individuals with congenital deafness. Most patients with cochlear malformations remain etiologically undiagnosed due to insufficient knowledge about underlying genes or the inability to make conclusive interpretations of identified genetic variants. We used exome sequencing for genetic evaluation of hearing loss associated with cochlear malformations in three probands from unrelated families. We subsequently generated monoclonal induced pluripotent stem cell (iPSC) lines, bearing patient-specific knockins and knockouts using CRISPR/Cas9 to assess pathogenicity of candidate variants. We detected (p.Arg165Gly) and (p.Cys186Arg), variants of uncertain significance in two recognized genes for deafness, and (p.Trp574*) in a candidate gene. Upon differentiation of iPSCs towards inner ear organoids, we observed significant developmental aberrations in knockout lines compared to their isogenic controls. Patient-specific single nucleotide variants (SNVs) showed similar abnormalities as the knockout lines, functionally supporting their causality in the observed phenotype. Therefore, we present human inner ear organoids as a tool to rapidly validate the pathogenicity of DNA variants associated with cochlear malformations.
PubMed: 38947059
DOI: 10.21203/rs.3.rs-4474071/v1 -
MedRxiv : the Preprint Server For... Jun 2024In recent years, there has been increased focus on exploring the role the non-protein-coding genome plays in Mendelian disorders. One class of particular interest is...
In recent years, there has been increased focus on exploring the role the non-protein-coding genome plays in Mendelian disorders. One class of particular interest is long non-coding RNAs (lncRNAs), which has recently been implicated in the regulation of diverse molecular processes. However, because lncRNAs do not encode protein, there is uncertainty regarding what constitutes a pathogenic lncRNA variant, and thus annotating such elements is challenging. The Developmental Genome Anatomy Project (DGAP) and similar projects recruit individuals with apparently balanced chromosomal abnormalities (BCAs) that disrupt or dysregulate genes in order to annotate the human genome. We hypothesized that rearrangements disrupting lncRNAs could be the underlying genetic etiology for the phenotypes of a subset of these individuals. Thus, we assessed 279 cases with BCAs and selected 191 cases with simple BCAs (breakpoints at only two genomic locations) for further analysis of lncRNA disruptions. From these, we identified 66 cases in which the chromosomal rearrangements directly disrupt lncRNAs. Strikingly, the lncRNAs and are each disrupted in two unrelated cases. Furthermore, in 30 cases, no genes of any other class aside from lncRNAs are directly disrupted, consistent with the hypothesis that lncRNA disruptions could underly the phenotypes of these individuals. To showcase the power of this genomic approach for annotating lncRNAs, here we focus on clinical reports and genetic analysis of two individuals with BCAs and additionally highlight six individuals with likely developmental etiologies due to lncRNA disruptions.
PubMed: 38946951
DOI: 10.1101/2024.06.16.24307499