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Frontiers in Cellular Neuroscience 2024Mild traumatic brain injury (mTBI) resulting from low-intensity blast (LIB) exposure in military and civilian individuals is linked to enduring behavioral and cognitive...
Mild traumatic brain injury (mTBI) resulting from low-intensity blast (LIB) exposure in military and civilian individuals is linked to enduring behavioral and cognitive abnormalities. These injuries can serve as confounding risk factors for the development of neurodegenerative disorders, including Alzheimer's disease-related dementias (ADRD). Recent animal studies have demonstrated LIB-induced brain damage at the molecular and nanoscale levels. Nevertheless, the mechanisms linking these damages to cognitive abnormalities are unresolved. Challenges preventing the translation of preclinical studies into meaningful findings in "real-world clinics" encompass the heterogeneity observed between different species and strains, variable time durations of the tests, quantification of dosing effects and differing approaches to data analysis. Moreover, while behavioral tests in most pre-clinical studies are conducted at the group level, clinical tests are predominantly assessed on an individual basis. In this investigation, we advanced a high-resolution and sensitive method utilizing the CognitionWall test system and applying reversal learning data to the Boltzmann fitting curves. A flow chart was developed that enable categorizing individual mouse to different levels of learning deficits and patterns. In this study, rTg4510 mice, which represent a neuropathology model due to elevated levels of tau P301L, together with the non-carrier genotype were exposed to LIB. Results revealed distinct and intricate patterns of learning deficits and patterns within each group and in relation to blast exposure. With the current findings, it is possible to establish connections between mice with specific cognitive deficits to molecular changes. This approach can enhance the translational value of preclinical findings and also allow for future development of a precision clinical treatment plan for ameliorating neurologic damage of individuals with mTBI.
PubMed: 38948027
DOI: 10.3389/fncel.2024.1397046 -
Oncology Research 2024Inflammatory myofibroblastic tumor (IMT) is a rare neoplasm with intermediate malignancy characterized by a propensity for recurrence but a low metastatic rate.... (Review)
Review
Inflammatory myofibroblastic tumor (IMT) is a rare neoplasm with intermediate malignancy characterized by a propensity for recurrence but a low metastatic rate. Diagnostic challenges arise from the diverse pathological presentation, variable symptomatology, and lack of different imaging features. However, IMT is identified by the fusion of the anaplastic lymphoma kinase (ALK) gene, which is present in approximately 70% of cases, with various fusion partners, including ran-binding protein 2 (RANBP2), which allows confirmation of the diagnosis. While surgery is the preferred approach for localized tumors, the optimal long-term treatment for advanced or metastatic disease is difficult to define. Targeted therapies are crucial for achieving sustained response to treatment within the context of genetic alteration in IMT. Crizotinib, an ALK tyrosine kinase inhibitor (TKI), was officially approved by the US Food and Drug Administration (FDA) in 2020 to treat IMT with ALK rearrangement. However, most patients face resistance and disease progression, requiring consideration of sequential treatments. Combining radiotherapy with targeted therapy appears to be beneficial in this indication. Early promising results have also been achieved with immunotherapy, indicating potential for combined therapy approaches. However, defined recommendations are still lacking. This review analyzes the available research on IMT, including genetic disorders and their impact on the course of the disease, data on the latest targeted therapy regimens and the possibility of developing immunotherapy in this indication, as well as summarizing general knowledge about prognostic and predictive factors, also in terms of resistance to systemic therapy.
PubMed: 38948020
DOI: 10.32604/or.2024.050350 -
Bioinformatics Advances 2024The data sharing of large comprehensive cancer research projects, such as The Cancer Genome Atlas (TCGA), has improved the availability of high-quality data to research...
MOTIVATION
The data sharing of large comprehensive cancer research projects, such as The Cancer Genome Atlas (TCGA), has improved the availability of high-quality data to research labs around the world. However, due to the volume and inherent complexity of high-throughput omics data, analysis of this is limited by the capacity for performing data processing through programming languages such as R or Python. Existing webtools lack functionality that supports large-scale analysis; typically, users can only input one gene, or a gene list condensed into a gene set, instead of individual gene-level analysis. Furthermore, analysis results are usually displayed without other sample-level molecular or clinical annotations. To address these gaps in the existing webtools, we have developed Evergene using R and Shiny.
RESULTS
Evergene is a user-friendly webtool that utilizes RNA-sequencing data, alongside other sample and clinical annotation, for large-scale gene-centric analysis, including principal component analysis (PCA), survival analysis (SA), and correlation analysis (CA). Moreover, Evergene achieves in-depth analysis of cancer transcriptomic data which can be explored through dimensional reduction methods, relating gene expression with clinical events or other sample information, such as ethnicity, histological classification, and molecular indices. Lastly, users can upload custom data to Evergene for analysis.
AVAILABILITY AND IMPLEMENTATION
Evergene webtool is available at https://bshihlab.shinyapps.io/evergene/. The source code and example user input dataset are available at https://github.com/bshihlab/evergene.
PubMed: 38948009
DOI: 10.1093/bioadv/vbae092 -
World Journal of Clinical Pediatrics Jun 2024Preterm birth is the leading cause of mortality in newborns, with very-low-birth-weight infants usually experiencing several complications. Breast milk is considered the...
BACKGROUND
Preterm birth is the leading cause of mortality in newborns, with very-low-birth-weight infants usually experiencing several complications. Breast milk is considered the gold standard of nutrition, especially for preterm infants with delayed gut colonization, because it contains beneficial microorganisms, such as and .
AIM
To analyze the gut microbiota of breastfed preterm infants with a birth weight of 1500 g or less.
METHODS
An observational study was performed on preterm infants with up to 36.6 wk of gestation and a birth weight of 1500 g or less, born at the University Hospital Dr. José Eleuterio González at Monterrey, Mexico. A total of 40 preterm neonates were classified into breast milk feeding (BM) and mixed feeding (MF) groups (21 in the BM group and 19 in the MF group), from October 2017 to June 2019. Fecal samples were collected before they were introduced to any feeding type. After full enteral feeding was achieved, the composition of the gut microbiota was analyzed using 16S rRNA gene sequencing. Numerical variables were compared using Student's -test or using the Mann-Whitney test for nonparametric variables. Dominance, evenness, equitability, Margalef's index, Fisher's alpha, Chao-1 index, and Shannon's diversity index were also calculated.
RESULTS
No significant differences were observed at the genus level between the groups. Class comparison indicated higher counts of and in the initial compared to the final sample of the BM group ( < 0.011). In addition, higher counts of were detected in the final than in the initial sample ( = 0.040). According to the Margalef index, Fisher's alpha, and Chao-1 index, a decrease in species richness from the initial to the final sample, regardless of the feeding type, was observed ( < 0.050). The four predominant phyla were , and with being the most abundant. However, no significant differences were observed between the initial and final samples at the phylum level.
CONCLUSION
Breastfeeding is associated with a decrease in and and an increase of , contributing to the literature of the gut microbiota structure of very low-birth-weight, preterm.
PubMed: 38947995
DOI: 10.5409/wjcp.v13.i2.90499 -
Frontiers in Chemistry 2024Non-plasma technologies are being extensively investigated for their potential to mitigate microbial growth through the production of various reactive species....
Non-plasma technologies are being extensively investigated for their potential to mitigate microbial growth through the production of various reactive species. Predominantly, studies utilise atmospheric non-thermal plasma to produce plasma-activated liquids. The advancement of plasma-liquid applications has led to the investigation of plasma-activated aerosols (PAAs). This study aimed to produce a rapid-prototyped plasma-activated aerosol setup and perform chemical and anti-bacterial characterisation on the resultant activated aerosols. The setup was produced using stereolithography 3D printing, and air was used as the carrier gas. The novel design of the device allowed for the direct production of PAAs without the prior generation of plasma-activated water and subsequent aerosolisation. The generated PAAs were assessed for nitrite, hydrogen peroxide and ozone content using colourimetric assays. Anti-bacterial efficacy was tested against three human pathogenic strains: , , and . It was observed that nitrite and ozone contact concentration increased with exposure time, yet no hydrogen peroxide was detected. The generated PAAs showed significant zones of no growth for all bacterial strains. These devices, therefore, show potential to be used as anti-bacterial disinfection technologies.
PubMed: 38947958
DOI: 10.3389/fchem.2024.1416982 -
Frontiers in Oncology 2024Treatment intensification with androgen deprivation therapy (ADT) and androgen receptor pathway inhibitors (ARPi) have led to improved survival in advanced prostate...
Treatment intensification with androgen deprivation therapy (ADT) and androgen receptor pathway inhibitors (ARPi) have led to improved survival in advanced prostate cancer. However, ADT is linked to significant cardiovascular toxicity, and ARPi also negatively impacts cardiovascular health. Together with a higher prevalence of baseline cardiovascular risk factors reported among prostate cancer survivors at diagnosis, there is a pressing need to prioritise and optimise cardiovascular health in this population. Firstly, While no dedicated cardiovascular toxicity risk calculators are available, other tools such as SCORE2 can be used for baseline cardiovascular risk assessment. Next, selected patients on combination therapy may benefit from de-escalation of ADT to minimise its toxicities while maintaining cancer control. These patients can be characterised by an exceptional PSA response to hormonal treatment, favourable disease characteristics and competing comorbidities that warrant a less aggressive treatment regime. In addition, emerging molecular and genomic biomarkers hold the potential to identify patients who are suited for a de-escalated treatment approach either with ADT or with ARPi. One such biomarker is AR-V7 splice variant that predicts resistance to ARPi. Lastly, optimization of modifiable cardiovascular risk factors for patients through a coherent framework (ABCDE) and exercise therapy is equally important. This article aims to comprehensively review the cardiovascular impact of hormonal manipulation in metastatic hormone-sensitive prostate cancer, propose overarching strategies to mitigate cardiovascular toxicity associated with hormonal treatment, and, most importantly, raise awareness about the detrimental cardiovascular effects inherent in our current management strategies involving hormonal agents.
PubMed: 38947889
DOI: 10.3389/fonc.2024.1386597 -
Nature Cardiovascular Research Oct 2023Among the diverse populations of myeloid cells that reside within the healthy and diseased heart, C-C chemokine receptor 2 (CCR2) is specifically expressed on...
Among the diverse populations of myeloid cells that reside within the healthy and diseased heart, C-C chemokine receptor 2 (CCR2) is specifically expressed on inflammatory populations of monocytes and macrophages that contribute to the development and progression of heart failure. Here, we evaluated a peptide-based imaging probe (Cu-DOTA-ECL1i) that specifically recognizes CCR2 monocytes and macrophages for human cardiac imaging. Compared to healthy controls, Cu-DOTA-ECL1i heart uptake was increased in subjects following acute myocardial infarction, predominately localized within the infarct area, and was associated with impaired myocardial wall motion. These findings establish the feasibility of molecular imaging of CCR2 expression to visualize inflammatory monocytes and macrophages in the injured human heart.
PubMed: 38947883
DOI: No ID Found -
Journal of Extracellular Biology Jul 2024Neuroinflammation is initiated through microglial activation and cytokine release which can be induced through lipopolysaccharide treatment (LPS) leading to a...
Neuroinflammation is initiated through microglial activation and cytokine release which can be induced through lipopolysaccharide treatment (LPS) leading to a transcriptional cascade culminating in the differential expression of target proteins. These differentially expressed proteins can then be packaged into extracellular vesicles (EVs), a form of cellular communication, further propagating the neuroinflammatory response over long distances. Despite this, the EV proteome in the brain, following LPS treatment, has not been investigated. Brain tissue and brain derived EVs (BDEVs) isolated from the cortex of LPS-treated mice underwent thorough characterisation to meet the minimal information for studies of extracellular vesicles guidelines before undergoing mass spectrometry analysis to identify the differentially expressed proteins. Fourteen differentially expressed proteins were identified in the LPS brain tissue samples compared to the controls and 57 were identified in the BDEVs isolated from the LPS treated mice compared to the controls. This included proteins associated with the initiation of the inflammatory response, epigenetic regulation, and metabolism. These results allude to a potential link between small EV cargo and early inflammatory signalling.
PubMed: 38947878
DOI: 10.1002/jex2.165 -
ACS Omega Jun 2024Previous studies have demonstrated the regulatory roles of Transmembrane protein 147 (TMEM147) in various diseases, including cancer. However, systematic pan-cancer...
Previous studies have demonstrated the regulatory roles of Transmembrane protein 147 (TMEM147) in various diseases, including cancer. However, systematic pan-cancer analyses investigating the role of TMEM147 in diagnosis, prognosis, and immunological prediction are lacking. An analysis of data from The Cancer Genome Atlas (TCGA) revealed differential TMEM147 expression across various types of cancer as well as within immune and molecular cancer subtypes. Moreover, high TMEM147 expression was associated with poor disease-specific survival (DSS), overall survival (OS), and progression-free interval (PFI) across cancers, suggesting its potential as a prognostic biomarker. Our study further revealed a significant correlation between TMEM147 expression and T helper cell and Tcm cell infiltration in most cancer types. In the case of liver hepatocellular carcinoma (LIHC), the effect of TMEM147 on prognosis varied among different clinical subtypes. Additionally, functional enrichment analysis revealed an association between TMEM147 and metabolic pathways. Finally, experiments on the MIHA cell line and four LIHC cell lines confirmed the role of TMEM147 in promoting liver cancer cell proliferation, further confirming the clinical value of TMEM147 in liver cancer diagnosis. Our findings suggest that TMEM147 may serve as a diagnostic and prognostic biomarker across cancers while also playing a significant role in LIHC.
PubMed: 38947838
DOI: 10.1021/acsomega.4c01215 -
ACS Omega Jun 2024is the third most common infectious pathogen in AIDS patients and leads to the highest death rate in Guangxi, China. The lack of reliable biomarkers is one of the major...
is the third most common infectious pathogen in AIDS patients and leads to the highest death rate in Guangxi, China. The lack of reliable biomarkers is one of the major obstacles in current clinical diagnosis, which largely contributes to this high mortality. Here, we present a study that aimed at identifying diagnostic biomarker candidates through genome-wide prediction and functional annotation of secreted proteins. A total of 584 secreted proteins then emerged, including 382 classical and 202 nonclassical ones. Among them, there were 87 newly obtained functional annotations in this study. The annotated proteins were further evaluated by combining RNA profiling and a homology comparison. Three proteins were ultimately highlighted as biomarker candidates with robust expression and remarkable specificity. The predicted phosphoinositide phospholipase C and the galactomannoprotein were suggested to play an interactive immune game through metabolism of arachidonic acid. Therefore, they hold promise in developing new tools for clinical diagnosis of and also possibly serve as molecular targets for future therapy.
PubMed: 38947822
DOI: 10.1021/acsomega.4c00571