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Cureus May 2024Hypertension (HTN), a leading risk factor for cardiovascular diseases, is intricately linked with endothelial dysfunction, a hallmark of vascular pathology. The effect...
INTRODUCTION
Hypertension (HTN), a leading risk factor for cardiovascular diseases, is intricately linked with endothelial dysfunction, a hallmark of vascular pathology. The effect of oxidative stress in maintaining the optimum endothelial function in the regulation of blood pressure is yet to be explored. While numerous factors contribute to the pathogenesis of HTN, emerging evidence highlights the pivotal role of oxidative stress in endothelial dysfunction, offering novel insights into the underlying mechanisms.
AIM
Our study delves into the multifaceted relationship between oxidative stress and endothelial dysfunction in HTN, elucidating key molecular pathways and potential therapeutic avenues. Our study aims to find out the association between oxidative stress and endothelial function in the regulation of blood pressure.
METHODS
A total of 108 age-matched participants of both genders were divided into three groups by following the guidelines of the American Heart Association (AHA) classification for HTN. Blood pressure was recorded manually in resting posture three times at an interval of 10 minutes using a sphygmomanometer after providing 10 minutes of rest before the first reading. Parameters of oxidative stress and endothelial function were measured by using a UV spectrophotometer. Our study results were depicted as mean ± SD.
RESULTS
The correlation between our variables was performed using Spearman's correlation considering the value of p<0.05 as statistically significant. Serum malondialdehyde (MDA), a parameter of oxidative stress, was found to be increasing and serum nitric oxide (NO), a parameter to assess endothelial function, was found to be decreasing as the blood pressure increased. These observations are indicative that optimal oxidative stress and optimal endothelial function are required to maintain normal blood pressure regardless of gender.
CONCLUSIONS
All persons who are suspected of future cardiovascular risks should be regularly checked for these parameters to avoid cardiovascular morbidity such as HTN.
PubMed: 38939274
DOI: 10.7759/cureus.61245 -
Advances in Laboratory Medicine Jun 2024Pyruvate carboxylase, a mitochondrial enzyme, catalyses the conversion of glycolytic end-product pyruvate to tricarboxylic acid cycle intermediate, oxaloacetate. Rare...
OBJECTIVES
Pyruvate carboxylase, a mitochondrial enzyme, catalyses the conversion of glycolytic end-product pyruvate to tricarboxylic acid cycle intermediate, oxaloacetate. Rare pyruvate carboxylase deficiency manifests in three clinical and biochemical phenotypes: neonatal onset type A, infantile onset type B and a benign C type. The objective of this case series is to expand the knowledge of overlapping clinical and biochemical phenotypes of pyruvate carboxylase deficiency.
CASE PRESENTATION
We report three Sri Lankan neonates including two siblings, of two unrelated families with pyruvate carboxylase deficiency. All three developed respiratory distress within the first few hours of birth. Two siblings displayed typical biochemical findings reported in type B. The other proband with normal citrulline, lysine, moderate lactate, paraventricular cystic lesions, bony deformities, and a novel missense, homozygous variant c.2746G>C [p.(Asp916His)] in the gene, biochemically favoured type A.
CONCLUSIONS
Our findings indicate the necessity of prompt laboratory investigations in a tachypneic neonate with coexisting metabolic acidosis, as early recognition is essential for patient management and family counselling. Further case studies are required to identify overlapping symptoms and biochemical findings in different types of pyruvate carboxylase deficiency phenotypes.
PubMed: 38939194
DOI: 10.1515/almed-2023-0102 -
Journal of Extracellular Biology Jul 2023High-resolution computed tomography (HRCT) imaging is critical for diagnostic evaluation of Idiopathic Pulmonary Fibrosis (IPF). However, several other interstitial lung...
High-resolution computed tomography (HRCT) imaging is critical for diagnostic evaluation of Idiopathic Pulmonary Fibrosis (IPF). However, several other interstitial lung diseases (ILDs) often exhibit radiologic pattern similar to IPF on HRCT making the diagnosis of the disease difficult. Therefore, biomarkers that distinguish IPF from other ILDs can be a valuable aid in diagnosis. Using mass spectrometry, we performed proteomic analysis of plasma extracellular vesicles (EVs) in patients diagnosed with IPF, chronic hypersensitivity pneumonitis, nonspecific interstitial pneumonitis, and healthy subjects. A five-protein signature was identified by lasso regression and was validated in an independent cohort using ELISA. The five-protein signature derived from mass spectrometry data showed an area under the receiver operating characteristic curve of 0.915 (95%CI: 0.819-1.011) and 0.958 (95%CI: 0.882-1.034) for differentiating IPF from other ILDs and from healthy subjects, respectively. Stepwise backwards elimination yielded a model with 3 and 2 proteins for discriminating IPF from other ILDs and healthy subjects, respectively, without compromising diagnostic accuracy. In summary, we discovered and validated EV protein biomarkers for differential diagnosis of IPF in independent cohorts. Interestingly, the biomarker panel could also distinguish IPF and healthy subjects with high accuracy. The biomarkers need to be evaluated in large prospective cohorts to establish their clinical utility.
PubMed: 38939072
DOI: 10.1002/jex2.98 -
Molecular Therapy. Nucleic Acids Sep 2024Effective therapeutics are necessary for managing severe COVID-19 disease despite the availability of vaccines. Small interfering RNA (siRNA) can silence viral genes and...
Effective therapeutics are necessary for managing severe COVID-19 disease despite the availability of vaccines. Small interfering RNA (siRNA) can silence viral genes and restrict SARS-CoV-2 replication. Cell-penetrating peptides is a robust method for siRNA delivery, enhancing siRNA stability and targeting specific receptors. We developed a peptide HE25 that blocks SARS-CoV-2 replication by various mechanisms, including the binding of multiple receptors involved in the virus's internalization, such as ACE2, integrins and NRP1. HE25 not only acts as a vehicle to deliver the SARS-CoV-2 RNA-dependent RNA polymerase siRNA into cells but also facilitates their internalization through endocytosis. Once inside endosomes, the siRNA is released into the cytoplasm through the Histidine-proton sponge effect and the selective cleavage of HE25 by cathepsin B. These mechanisms effectively inhibited the replication of the ancestral SARS-CoV-2 and the Omicron variant BA.5 . When HE25 was administered , either by intravenous injection or inhalation, it accumulated in lungs, veins and arteries, endothelium, or bronchial structure depending on the route. Furthermore, the siRNA/HE25 complex caused gene silencing in lung cells . The SARS-CoV-2 siRNA/HE25 complex is a promising therapeutic for COVID-19, and a similar strategy can be employed to combat future emerging viral diseases.
PubMed: 38939051
DOI: 10.1016/j.omtn.2024.102227 -
JACC. Advances Jul 2023Obesity cardiomyopathy (OCM) can be associated with sudden cardiac death (SCD) but its pathologic features are not well described.
BACKGROUND
Obesity cardiomyopathy (OCM) can be associated with sudden cardiac death (SCD) but its pathologic features are not well described.
OBJECTIVES
The objective of this study was to characterize the clinical and pathological features of OCM associated with SCD.
METHODS
This was a retrospective case control autopsy study. OCM was identified by an increased heart weight (>550 g in males; >450 g in females) in individuals with obesity (body mass index [BMI] ≥30 kg/m) in the absence of other causes. Cases of OCM with SCD were compared to sex and age matched SCD controls with obesity or with normal weight (BMI 18.5-24.9 kg/m) and morphologically normal hearts. Autopsy measures included: heart weight, atrial dimensions, ventricular wall thickness, and epicardial adipose tissue. Fibrosis was assessed microscopically.
RESULTS
Of 6,457 SCD cases, 53 cases of OCM were identified and matched to 106 controls with obesity and 106 normal weight controls. The OCM mean age at death of individuals with OCM was 42 ± 12 with a male predominance (n = 34, 64%). Males died younger than females (40 ± 13 vs 45 ± 10, = 0.036). BMI was increased in OCM cases compared to controls with obesity (42 ± 8 vs 35 ± 5). The average heart weight was 598 ± 93 g in OCM. There were increases in right and left ventricular wall thickness (all < 0.05) in OCM cases compared to controls. Right ventricular epicardial fat was increased in OCM compared to normal weight controls only. Left ventricular fibrosis was identified in 7 (13%) cases.
CONCLUSIONS
OCM may be a specific pathological entity associated with SCD. It is most commonly seen in young males with increased BMI.
PubMed: 38938994
DOI: 10.1016/j.jacadv.2023.100414 -
Journal of Extracellular Biology Jun 2023Small RNA (sRNA) profiling of Extracellular Vesicles (EVs) by Next-Generation Sequencing (NGS) often delivers poor outcomes, independently of reagents, platforms or...
Small RNA (sRNA) profiling of Extracellular Vesicles (EVs) by Next-Generation Sequencing (NGS) often delivers poor outcomes, independently of reagents, platforms or pipelines used, which contributes to poor reproducibility of studies. Here we analysed pre/post-sequencing quality controls (QC) to predict issues potentially biasing biological sRNA-sequencing results from purified human milk EVs, human and mouse EV-enriched plasma and human paraffin-embedded tissues. Although different RNA isolation protocols and NGS platforms were used in these experiments, all datasets had samples characterized by a marked removal of reads after pre-processing. The extent of read loss between individual samples within a dataset did not correlate with isolated RNA quantity or sequenced base quality. Rather, cDNA electropherograms revealed the presence of a constant peak whose intensity correlated with the degree of read loss and, remarkably, with the percentage of adapter dimers, which were found to be overrepresented sequences in high read-loss samples. The analysis through a QC pipeline, which allowed us to monitor quality parameters in a step-by-step manner, provided compelling evidence that adapter dimer contamination was the main factor causing batch effects. We concluded this study by summarising peer-reviewed published workflows that perform consistently well in avoiding adapter dimer contamination towards a greater likelihood of sequencing success.
PubMed: 38938917
DOI: 10.1002/jex2.91 -
Frontiers in Cardiovascular Medicine 2024Malignant mesothelioma (MM) is a rare and aggressive tumor that is found in the pleura and peritoneum. A few cases of MM in the pericardium and tunica vaginalis testis...
BACKGROUND
Malignant mesothelioma (MM) is a rare and aggressive tumor that is found in the pleura and peritoneum. A few cases of MM in the pericardium and tunica vaginalis testis have been reported. Moreover, primary occurrence in the atrium is extremely rare. The visual appearance of this tumor is similar to that of a common atrial myxoma, which makes it challenging for clinicians and radiologists to diagnose and treat this disease.
CASE DEMONSTRATION
An 18-year-old woman presented with symptoms of chest pain, shortness of breath, cough, and expectoration for 7 days. Echocardiography was performed on the patient, which revealed an atrial mass. Myxoma was one of the differential diagnoses. The tumor was an elliptical mass with tips, and the cut surface was jelly-like, similar to myxoma. After surgery, a pathologic examination of the biopsied tumor confirmed epithelial-type MM. During postoperative follow-up, no recurrence of the tumor was observed.
CONCLUSIONS
MM originating in the atrium is considered to be extremely rare. Consequently, clinicians can easily misdiagnose atrial MM as a myxoma. Moreover, to confirm the diagnosis, histopathologic biopsy, histomorphological characterization, immunohistochemistry, and molecular genetic testing are required. Therefore, clinical diagnosis and treatment of MM are challenging.
PubMed: 38938650
DOI: 10.3389/fcvm.2024.1398311 -
PeerJ 2024While the significance of immunogenic cell death (ICD) in oncology is acknowledged, its specific impact on colorectal carcinoma remains underexplored. In this study, we...
While the significance of immunogenic cell death (ICD) in oncology is acknowledged, its specific impact on colorectal carcinoma remains underexplored. In this study, we delved into the role of ICD in colorectal carcinoma, a topic not yet comprehensively explored. A novel ICD quantification system was developed to forecast patient outcomes and the effectiveness of immunotherapy. Utilizing single-cell sequencing, we constructed an ICD score within the tumor immune microenvironment (TIME) and examined immunogenic cell death related genes (ICDRGs). Using data from TCGA and GEO, we discovered two separate molecular subcategories within 1,184 patients diagnosed with colon adenocarcinoma/rectum adenocarcinoma (COADREAD). The ICD score was established by principal component analysis (PCA), which classified patients into groups with low and high ICD scores. Further validation in three independent cohorts confirmed the model's accuracy in predicting immunotherapy success. Patients with higher ICD scores exhibited a "hot" immune phenotype and showed increased responsiveness to immunotherapy. Key genes in the model, such as , , , and , were found to enhance COADREAD cell proliferation, invasion, and expression. These insights offered a new avenue for anti-tumor strategies by targeting ICD, marking advances in colorectal carcinoma treatment.
Topics: Humans; Colorectal Neoplasms; Immunogenic Cell Death; Prognosis; Tumor Microenvironment; Immunotherapy; Gene Expression Profiling; Male; Female; Adenocarcinoma; Middle Aged; Biomarkers, Tumor; Principal Component Analysis; Gene Expression Regulation, Neoplastic
PubMed: 38938617
DOI: 10.7717/peerj.17629 -
Frontiers in Immunology 2024This study discusses the importance of minimal residual disease (MRD) detection in acute myeloid leukemia (AML) patients using liquid biopsy and next-generation...
This study discusses the importance of minimal residual disease (MRD) detection in acute myeloid leukemia (AML) patients using liquid biopsy and next-generation sequencing (NGS). AML prognosis is based on various factors, including genetic alterations. NGS has revealed the molecular complexity of AML and helped refine risk stratification and personalized therapies. The long-term survival rates for AML patients are low, and MRD assessment is crucial in predicting prognosis. Currently, the most common methods for MRD detection are flow cytometry and quantitative PCR, but NGS is being incorporated into clinical practice due to its ability to detect genomic aberrations in the majority of AML patients. Typically, bone marrow samples are used for MRD assessment, but using peripheral blood samples or liquid biopsies would be less invasive. Leukemia originates in the bone marrow, along with the cfDNA obtained from peripheral blood. This study aimed to assess the utility of cell-free DNA (cfDNA) from peripheral blood samples for MRD detection in AML patients. A cohort of 20 AML patients was analyzed using NGS, and a correlation between MRD assessment by cfDNA and circulating tumor cells (CTCs) in paired samples was observed. Furthermore, a higher tumor signal was detected in cfDNA compared to CTCs, indicating greater sensitivity. Challenges for the application of liquid biopsy in MRD assessment were discussed, including the selection of appropriate markers and the sensitivity of certain markers. This study emphasizes the potential of liquid biopsy using cfDNA for MRD detection in AML patients and highlights the need for further research in this area.
Topics: Neoplasm, Residual; Humans; Leukemia, Myeloid, Acute; High-Throughput Nucleotide Sequencing; Neoplastic Cells, Circulating; Male; Female; Middle Aged; Liquid Biopsy; Adult; Biomarkers, Tumor; Aged; Prognosis; Cell-Free Nucleic Acids
PubMed: 38938565
DOI: 10.3389/fimmu.2024.1252258 -
Open Veterinary Journal May 2024Although relatively uncommon, lymphoma is the most prevalent haematopoietic neoplasia in horses, and multicentric lymphoma remains the most common presentation of the...
BACKGROUND
Although relatively uncommon, lymphoma is the most prevalent haematopoietic neoplasia in horses, and multicentric lymphoma remains the most common presentation of the disease. The pathogenesis of equine lymphoma is still poorly understood and the diagnosis is usually confirmed at an advanced stage of the disease, compromising the prognosis. This study investigated the clinical, pathological, and molecular features of a case of equine multicentric lymphoma.
CASE DESCRIPTION
An apparently healthy 5-year-old crossbreed mare hospitalized at the Centre of Animal Reproduction of Vairão, Portugal, suddenly presented clinical signs of supraorbital oedema and mandibular lymph node enlargement, developing fever, facial oedema, and generalized lymphadenopathy. The mare ended up dying twenty-four days after the first clinical signs due to multisystem organ failure. Haematological and biochemical analyses, necropsy, and microscopic and molecular evaluation of affected tissues were performed. At necropsy, the main findings were multiple multinodular lesions, distributed along the serous surface of oropharynx, trachea, pericardium, gastrointestinal tract, and mesentery. Microscopically, these consisted of solid proliferations of neoplastic round cells that exhibited immunopositivity for CD3 (T cells). Based on these findings, a medium-grade multicentric T-cell lymphoma was diagnosed.
CONCLUSION
There is still very little research regarding the molecular characterization of lymphoma in horses. As an entity itself is quite heterogeneous, it is important to describe the interspecies particularities to understand its development and behaviour.
Topics: Horses; Animals; Horse Diseases; Female; Fatal Outcome; Lymphoma; Portugal; Lymphoma, T-Cell
PubMed: 38938428
DOI: 10.5455/OVJ.2024.v14.i5.24