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International Journal of Molecular... Jun 2024Proteomics offers a robust method for quantifying proteins and elucidating their roles in cellular functions, surpassing the insights provided by transcriptomics. The...
Proteomics offers a robust method for quantifying proteins and elucidating their roles in cellular functions, surpassing the insights provided by transcriptomics. The Clinical Proteomic Tumor Analysis Consortium database, enriched with comprehensive cancer proteomics data including phosphorylation and ubiquitination profiles, alongside transcriptomics data from the Genomic Data Commons, allow for integrative molecular studies of cancer. The ProteoCancer Analysis Suite (PCAS), our newly developed R package and Shinyapp, leverages these resources to facilitate in-depth analyses of proteomics, phosphoproteomics, and transcriptomics, enhancing our understanding of the tumor microenvironment through features like immune infiltration and drug sensitivity analysis. This tool aids in identifying critical signaling pathways and therapeutic targets, particularly through its detailed phosphoproteomic analysis. To demonstrate the functionality of the PCAS, we conducted an analysis of GAPDH across multiple cancer types, revealing a significant upregulation of protein levels, which is consistent with its important biological and clinical significance in tumors, as indicated in our prior research. Further experiments were used to validate the findings performed using the tool. In conclusion, the PCAS is a powerful and valuable tool for conducting comprehensive proteomic analyses, significantly enhancing our ability to uncover oncogenic mechanisms and identify potential therapeutic targets in cancer research.
Topics: Humans; Proteomics; Neoplasms; Tumor Microenvironment; Software; Computational Biology; Proteome
PubMed: 38928396
DOI: 10.3390/ijms25126690 -
International Journal of Molecular... Jun 2024The maturation of HIV-1 virions is a crucial process in viral replication. Although T-cells are a primary source of virus production, much of our understanding of virion...
The maturation of HIV-1 virions is a crucial process in viral replication. Although T-cells are a primary source of virus production, much of our understanding of virion maturation comes from studies using the HEK293T human embryonic kidney cell line. Notably, there is a lack of comparative analyses between T-cells and HEK293T cells in terms of virion maturation efficiency in existing literature. We previously developed an advanced virion visualization system based on the FRET principle, enabling the effective distinction between immature and mature virions via fluorescence microscopy. In this study, we utilized pseudotyped, single-round infectious viruses tagged with FRET labels (HIV-1 Gag-iFRET∆Env) derived from Jurkat (a human T-lymphocyte cell line) and HEK293T cells to evaluate their virion maturation rates. HEK293T-derived virions demonstrated a maturity rate of 81.79%, consistent with other studies and our previous findings. However, virions originating from Jurkat cells demonstrated a significantly reduced maturation rate of 68.67% ( < 0.0001). Correspondingly, viruses produced from Jurkat cells exhibited significantly reduced infectivity compared to those derived from HEK293T cells, with the relative infectivity measured at 65.3%. This finding is consistent with the observed relative maturation rate of viruses produced by Jurkat cells. These findings suggest that initiation of virion maturation directly correlates with viral infectivity. Our observation highlights the dynamic nature of virus-host interactions and their implications for virion production and infectivity.
Topics: Humans; HIV-1; HEK293 Cells; Virion; Jurkat Cells; Fluorescence Resonance Energy Transfer; Virus Replication; Virus Assembly; HIV Infections
PubMed: 38928103
DOI: 10.3390/ijms25126396 -
International Journal of Molecular... Jun 2024Mutations have driven the evolution and development of new variants of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with potential implications for...
Mutations have driven the evolution and development of new variants of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with potential implications for increased transmissibility, disease severity and vaccine escape among others. Genome sequencing is a technique that allows scientists to read the genetic code of an organism and has become a powerful tool for studying emerging infectious diseases. Here, we conducted a cross-sectional study in selected districts of the Eastern Province of Zambia, from November 2021 to February 2022. We analyzed SARS-CoV-2 samples ( = 76) using high-throughput sequencing. A total of 4097 mutations were identified in 69 SARS-CoV-2 genomes with 47% (1925/4097) of the mutations occurring in the spike protein. We identified 83 unique amino acid mutations in the spike protein of the seven Omicron sublineages (BA.1, BA.1.1, BA.1.14, BA.1.18, BA.1.21, BA.2, BA.2.23 and XT). Of these, 43.4% (36/83) were present in the receptor binding domain, while 14.5% (12/83) were in the receptor binding motif. While we identified a potential recombinant XT strain, the highly transmissible BA.2 sublineage was more predominant (40.8%). We observed the substitution of other variants with the Omicron strain in the Eastern Province. This work shows the importance of pandemic preparedness and the need to monitor disease in the general population.
Topics: Zambia; Humans; SARS-CoV-2; COVID-19; Genome, Viral; Spike Glycoprotein, Coronavirus; Mutation; Cross-Sectional Studies; Retrospective Studies; Phylogeny; Genomics; High-Throughput Nucleotide Sequencing
PubMed: 38928045
DOI: 10.3390/ijms25126338 -
Cancers Jun 2024During the cell life cycle, extracellular vesicles (EVs) transport different cargos, including organelles, proteins, RNAs, DNAs, metabolites, etc., that influence cell... (Review)
Review
During the cell life cycle, extracellular vesicles (EVs) transport different cargos, including organelles, proteins, RNAs, DNAs, metabolites, etc., that influence cell proliferation and apoptosis in recipient cells. EVs from metastatic cancer cells remodel the extracellular matrix and cells of the tumor microenvironment (TME), promoting tumor invasion and metastatic niche preparation. Although the process is not fully understood, evidence suggests that EVs facilitate genetic material transfer between cells. In the context of NSCLC, EVs can mediate intercellular mitochondrial (Mt) transfer, delivering mitochondria organelle (MtO), mitochondrial DNA (mtDNA), and/or mtRNA/proteinaceous cargo signatures (MtS) through different mechanisms. On the other hand, certain populations of cancer cells can hijack the MtO from TME cells mainly by using tunneling nanotubes (TNTs). This transfer aids in restoring mitochondrial function, benefiting benign cells with impaired metabolism and enabling restoration of their metabolic activity. However, the impact of transferring mitochondria versus transplanting intact mitochondrial organelles in cancer remains uncertain and the subject of debate. Some studies suggest that EV-mediated mitochondria delivery to cancer cells can impact how cancer responds to radiation. It might make the cancer more resistant or more sensitive to radiation. In our review, we aimed to point out the current controversy surrounding experimental data and to highlight new paradigm-shifting modalities in radiation therapy that could potentially overcome cancer resistance mechanisms in NSCLC.
PubMed: 38927940
DOI: 10.3390/cancers16122235 -
Cancers Jun 2024Regulatory approval of immune checkpoint inhibitors (ICIs) was based on results of large, randomized clinical trials, resulting in limited outcomes data in patient...
Regulatory approval of immune checkpoint inhibitors (ICIs) was based on results of large, randomized clinical trials, resulting in limited outcomes data in patient cohorts typically underrepresented in such trials. The objective of this study was to evaluate the efficacy and safety of ICIs in these unique patient cohorts. This is a multicenter, retrospective analysis of real-world data at six academic and community clinics in the United States from 1 January 2011 to 1 April 2018. Patients were included if they had received at least one cycle of ICI treatment. Unique patient cohorts included age > 75 years, non-White race, positive smoking history, ECOG performance status (PS) ≥ 2, BMI ≥ 30 kg/m, autoimmune diseases (AIDs), chronic viral infections (CVI), extensive prior lines of therapy (LOTs), or >three metastatic sites. Immune-related adverse events (irAEs), overall survival (OS), and time to treatment failure were evaluated in the entire cohort and in NSCLC patients treated with PD-(L)1 monotherapy. Outcomes and their association with unique patient cohorts were compared on univariate analysis and multivariate analysis to those without a particular characteristic in the entire NSCLC PD-(L)1 monotherapy cohorts. In total, 1453 patients were included: 56.5%-smokers, 30.4%-non-White, 22.8%-elderly, 20.8%-ECOG PS ≥ 2, 15.7%-history of AIDs, and 4.7%-history of CVI. The common ICIs were nivolumab (37.1%) and pembrolizumab (22.2%). Black patients, compared to White patients, experienced fewer irAEs (OR 0.54, < 0.001). An ECOG PS of ≥2 (HR = 2.01, < 0.001) and an increased number of previous LOTs were associated with poor OS (the median OS of 26.2 vs. 16.2 vs. 9.6 months for one vs. two vs. three prior LOTs, < 0.001). The above results were confirmed in anti-PD-(L)1 monotherapy non-small cell lung cancer patients (n = 384). Overall, ICIs were safe and efficacious in these typically underrepresented patient cohorts. We noted ECOG PS ≥ 2 and an increased prior LOTs were associated with poor ICI efficacy, and Black patients, compared to White patients, experienced fewer irAEs.
PubMed: 38927928
DOI: 10.3390/cancers16122223 -
Bioengineering (Basel, Switzerland) Jun 2024Tumor organoid cultures play a crucial role in clinical practice, particularly in guiding medication by accurately determining the morphology and size of the organoids....
Tumor organoid cultures play a crucial role in clinical practice, particularly in guiding medication by accurately determining the morphology and size of the organoids. However, segmenting individual tumor organoids is challenging due to their inhomogeneous internal intensity and overlapping structures. This paper proposes a convexity-preserving level-set segmentation 4 model based on the characteristics of tumor organoid images to segment individual tumor organoids precisely. Considering the predominant spherical shape exhibited by organoid growth, we propose a level-set model that includes a data-driven term, a curvature term, and a regularization term. The data-driven term pulls the contour to the vicinity of the boundary; the curvature term ensures the maintenance of convexity in the targeted segmentation, and the regularization term controls the smoothness and propagation of the contour. The proposed model aids in overcoming interference from factors such as overlap and noise, enabling the evolving curve to converge to the actual boundary of the target accurately. Furthermore, we propose a selectable and targeted initialization method that guarantees precise segmentation of specific regions of interest. Experiments on 51 pancreatic ductal adenocarcinoma organoid images show that our model achieved excellent segmentation results. The average Dice value and computation time are 98.81±0.48% and 20.67 s. Compared with the C-V and CPLSE models, it is more accurate and takes less time.
PubMed: 38927837
DOI: 10.3390/bioengineering11060601 -
Bioengineering (Basel, Switzerland) May 2024This study aimed to evaluate walking independence in acute-care hospital patients using neural networks based on acceleration and angular velocity from two walking...
This study aimed to evaluate walking independence in acute-care hospital patients using neural networks based on acceleration and angular velocity from two walking tests. Forty patients underwent the 10-m walk test and the Timed Up-and-Go test at normal speed, with or without a cane. Physiotherapists divided the patients into two groups: 24 patients who were monitored or independent while walking with a cane or without aids in the ward, and 16 patients who were not. To classify these groups, the Transformer model analyzes the left gait cycle data from eight inertial sensors. The accuracy using all the sensor data was 0.836. When sensor data from the right ankle, right wrist, and left wrist were excluded, the accuracy decreased the most. When analyzing the data from these three sensors alone, the accuracy was 0.795. Further reducing the number of sensors to only the right ankle and wrist resulted in an accuracy of 0.736. This study demonstrates the potential of a neural network-based analysis of inertial sensor data for clinically assessing a patient's level of walking independence.
PubMed: 38927780
DOI: 10.3390/bioengineering11060544 -
Biomedicines Jun 2024DNA methylation may be a link between HIV, aging, and the increased risk of lung comorbidities. We investigated whether bronchoalveolar lavage (BAL) cells of people...
BACKGROUND
DNA methylation may be a link between HIV, aging, and the increased risk of lung comorbidities. We investigated whether bronchoalveolar lavage (BAL) cells of people living with HIV (PLWH) demonstrate epigenetic disruptions and advanced epigenetic aging.
METHODS
BAL cell DNA methylation from 25 PLWH and 16 HIV-uninfected individuals were tested for differential methylation of Alu and LINE-1 sites, markers of aging. We used a weighted gene correlation network analysis to identify HIV- and age-associated co-methylation networks. We tested the effect of HIV on DNA methylation using a robust linear model (false discovery rate < 0.10).
RESULTS
The BAL cells of PLWH were marked by global hypomethylation in both Alu and LINE-1 elements. Six co-methylated CpG networks were identified that were significantly associated with age; of these, the red module was significantly differentially methylated in PLWH and enriched pathways (e.g., Ras signaling and T-cell receptors). We identified 6428 CpG sites associated with HIV.
CONCLUSIONS
We have shown here for the first time that alterations in the DNA methylation of BAL cells in the lung with HIV show a pattern of advanced aging. This study strongly supports that HIV may contribute to an increased the risk of lung comorbidities through the epigenetics of aging.
PubMed: 38927468
DOI: 10.3390/biomedicines12061261 -
Antibiotics (Basel, Switzerland) Jun 2024Antimicrobial resistance (AMR) is a major public health threat linked to increased morbidity and mortality. It has the potential to return us to the pre-antibiotic era....
Antimicrobial resistance (AMR) is a major public health threat linked to increased morbidity and mortality. It has the potential to return us to the pre-antibiotic era. Antimicrobial stewardship (AMS) programs are recognized as a key intervention to improve antimicrobial use and combat AMR. However, implementation of AMS remains limited in Africa, particularly in Rwanda. This study aimed to assess prescription practices, identify areas for improvement, and promote adherence to AMS principles. Conducted at King Faisal Hospital in Rwanda, this qualitative study used semi-structured interviews with eight participants until saturation was reached. The interviews were recorded, transcribed, and thematically analyzed, revealing four emerging themes. The first theme was on AMS activities that were working well based on availability of microbiology laboratory results and prescription guidelines as factors influencing antibiotic prescription adjustments. The second theme was related to challenges during the implementation of the AMS program, including the prescription of broad-spectrum antibiotics, limited local data on AMR patterns, and stock-outs of essential antibiotics. The third theme was on the importance of adhering to AMR management guidelines at KFH. The last emerged on recommendations from participants centered on regular training for healthcare workers, widespread dissemination of AMR findings across departments, and the enforcement of antibiotic restriction policies. These actions can improve prescription behaviors, upholding the highest standards of patient care, and strengthening the nascent AMS program.
PubMed: 38927214
DOI: 10.3390/antibiotics13060548 -
BMC Public Health Jun 2024Illicit drug and high-risk alcohol use among adolescents leads to poor health outcomes. We enrolled adolescents from urban slums in Kampala, Uganda, to assess baseline...
BACKGROUND
Illicit drug and high-risk alcohol use among adolescents leads to poor health outcomes. We enrolled adolescents from urban slums in Kampala, Uganda, to assess baseline prevalence and factors associated with illicit drug and high-risk alcohol consumption.
METHODS
We conducted a cross-sectional study using data collected in a cohort that enrolled 14-19-year-old male and female participants from 25 March 2019 to 30 March 2020. Data was collected on social demographics, sexual behavior, and reproductive health using interviewer-administered questionnaires. The main outcomes were illicit drug use and high-risk alcohol use. Data on alcohol use was collected using the Alcohol Use Disorder Identification Test (AUDIT); results were dichotomized. Factors associated with each outcome were analyzed using multivariable logistic regression.
RESULTS
We enrolled 490 participants (60.6% female) with a median age of 18 (IQR 17-18) years, 84.9% had less than secondary education, 48.4% had their sexual debut before 15 years, 47.1% reported paid sex in the past 3 months and 22.8% had a sexually transmitted infection (chlamydia, gonorrhea, and active syphilis) baseline characteristics associated with illicit drug use in the past 3 months were male gender (aOR 12.45; 95% CI 7.21-21.50) being married (aOR 2.26; 95%CI 1.03-4.94) 10 or more paying sexual partners (aOR 2.45; 95%CI 1.05-5.69) and high-risk alcohol use (aOR 3.94; 95%CI 2.10-7.40), baseline characteristics associated with high-risk alcohol use were male gender (aOR 0.29; 95% CI 0.13-0.63) emotional violence from sexual partners (aOR 2.35; 95%CI 1.32-418) illicit drug users com (aOR 3.94; 95% CI 2.10-7.40).
CONCLUSION
Illicit drug and high-risk alcohol use are prevalent among male adolescents and adolescents involved in high-risk sexual behavior living in the urban slums of Kampala.
Topics: Humans; Adolescent; Male; Uganda; Female; Cross-Sectional Studies; Poverty Areas; Prevalence; Substance-Related Disorders; Illicit Drugs; Young Adult; Risk Factors; Sexual Behavior; Urban Population; Alcohol Drinking
PubMed: 38926824
DOI: 10.1186/s12889-024-19250-x