Impact of Omicron variant sublineage BA.2.75 on the OnSite COVID-19 Ag Rapid Test: the applicability of rapid antigen test with universal transport media.

BACKGROUND: Rapid antigen testing (RAT) is one of the most powerful tools for SARS-CoV-2 detection. The OnSite COVID-19 Ag Rapid Test is an antigen-based, point-of-care test approved by the WHO for Emergency Use Listing. The Nucleocapsid (N) gene mutations found in the emerging Omicron sublineages lead to the question of RAT performance. OBJECTIVE: To ensure the diagnostic performance of the study RAT during rapidly mutated Omicron variants. RESULTS: We independently evaluated the performance of this assay in 1098 archived samples collected in Thailand during October 2022-February 2023, which were 798 and 300 COVID-19 real-time RT-PCR positive and negative, respectively. The assay performed with 100% sensitivity and 100% specificity using a cycle threshold (Ct) of <20 for the RT-PCR. The sensitivity decreased to 88% when using Ct <30. Most of the SARS-CoV-2 found were Omicron BA.2 (99%), harboring six known N mutations (P13L, E31del, S33del, R203K, G204R and S413R). Eight samples containing hybrid variants (XBB.1*, XBB.2 and XBJ) were detected by the study RAT. This RAT detects all Omicron sublineages known to be circulating in Thailand. CONCLUSIONS: These results confirmed the good performance of the study RAT for detecting Omicron variants and its appropriateness for individual diagnosis and for genomic surveillance.

Cervical Cancer Markers: Epigenetics and microRNAs.

Gynecologic malignant neoplasms are a severe health problem among female patients, of which cervical cancer (CC), in particular, is a common disease leading to high mortality rates. Despite extensive attempts by researchers to solve the molecular mystery of CC, the mechanisms of its pathogenesis remain unclear. Tumor markers used in the clinical laboratory, such as squamous cell carcinoma (SCC), cancer antigen (CA)-125, and CA19-9, provide some help in diagnosing patients with CC. However, finding new molecular markers with high sensitivity and specificity is necessary. This review focuses on the role of epigenetic changes, particularly microRNAs (miRNAs), to CC. Several miRNAs that associated with CC potentially have the advantage of being early biomarkers. Moreover, altered serum miRNAs or single nucleotide polymorphisms in miRNA patterns may predict disease progression.

Inhibitory effect of oxidative damage on cardiomyocyte differentiation from Wharton's jelly-derived mesenchymal stem cells.

Ischemic heart diseases are a serious health problem worldwide. The transplantation of mesenchymal stem cells (MSCs) has been investigated in numerous clinical trials on various other diseases due to the self-renewal capacity of these cells and their potential to differentiate into a variety of cell types. The presence of excess reactive oxygen species in injured myocardium causes cardiac dysfunction and leads to inefficient repair of the heart. The poor outcomes of stem cell transplantation have been suggested to result from residual oxidative damage affecting the transplanted cells. The aim of the present study was to compare the effects of hydrogen peroxide (H2O2) on Wharton's jelly-derived MSCs (WJ-MSCs) and bone marrow-derived MSCs (BM-MSCs) in vitro, in order to provide information useful for the future selection of MSC types for cardiac differentiation and transplantation. H2O2 at concentrations of 200, 500 and 1,000 µM was applied to WJ-MSCs and BM-MSCs under cardiogenic differentiation conditions. The morphology of MSCs treated with H2O2 was similar to that of untreated cells, whereas the cell density decreased in direct association with the dose of H2O2. Cardiac differentiation markers were then evaluated by immunofluorescence analysis of GATA4 and cardiac troponin T (cTnT). The fluorescence intensity levels of the two markers were identified to be diminished by increasing doses of H2O2 from 500 to 1,000 µM. The expression levels of homeobox protein Nkx2.5, cTnT and cardiac α-actin were also examined, and were identified to be low in the WJ-MSCs treated with 1,000 µM H2O2, which was similar to the findings observed in BM-MSCs. These results suggested that oxidative stress affects cardiomyocyte differentiation via the downregulation of cardiac genes and cardiac proteins. Furthermore, it should be noted that there was a marked difference in the effect depending on the source of MSCs. This evidence provided supportive information for the use of stem cells in transplantation.

Prevalence of Anemia and Hemoglobin Disorders Among School Children in Myanmar.

The prevalence of anemia is high in the population of Myanmar and hypochromic microcytic anemia (HMA) is predominant. The objective of our study was to determine the prevalence of anemia and causes of HMA among school children. A cross-sectional study was conducted on 239 children from Thanlyin and Insein Townships, Yangon Region, Myanmar. Complete blood count (CBC) and blood film morphology was examined on venous blood samples. Hypochromic microcytic anemia cases were subsequently analyzed for serum ferritin and cellulose acetate hemoglobin (Hb) electrophoresis. The prevalence of anemia was 46.4%; 27.6% had mild, while 18.8% had moderate anemia, and no case of severe anemia was detected. The mean Hb concentration was 11.7 ± 0.9 g/dL. The younger age group (8-11 years) had a significantly higher prevalence of anemia than the older age group (12-15 years) (p = 0.029). Blood film morphology revealed a 50.6% red blood cell (RBC) disorder; HMA was the most common type (70.2%). Out of 85 children with HMA, three children (3.5%) had iron deficiency and all had comorbidity with Hb AE (ßA/ßE) (Hb E trait). Hemoglobin electrophoresis illustrated that Hb AA (ßA/ßA) (31, 36.5%) and Hb AE (ßA/ßE) trait (31, 36.5%) were the most common types followed by ß-thalassemia (ß-thal) trait (19, 22.3%) and Hb EE (ßE/ßE) (homozygous Hb E; HBB: c.79G>A) (three, 3.5%). Hematocrit [or packed cell volume (PCV)], mean corpuscular volume (MCV), mean corpuscular Hb (MCH) and mean corpuscular Hb concentration (MCHC), showed a significant difference between Hb AE, Hb EE and ß-thal trait (p = 0.029, 0.023, 0.015 and 0.01, respectively). Our findings will provide valuable information for the management of anemia in the Myanmar school-age population.

Molecular basis of human cerebral malaria development.

Cerebral malaria is still a deleterious health problem in tropical countries. The wide spread of malarial drug resistance and the lack of an effective vaccine are obstacles for disease management and prevention. Parasite and human genetic factors play important roles in malaria susceptibility and disease severity. The malaria parasite exerted a potent selective signature on the human genome, which is apparent in the genetic polymorphism landscape of genes related to pathogenesis. Currently, much genomic data and a novel body of knowledge, including the identification of microRNAs, are being increasingly accumulated for the development of laboratory testing cassettes for cerebral malaria prevention. Therefore, understanding of the underlying complex molecular basis of cerebral malaria is important for the design of strategy for cerebral malaria treatment and control.

p53 Regulates oxidative stress-mediated retrograde signaling: a novel mechanism for chemotherapy-induced cardiac injury.

The side effects of cancer therapy on normal tissues limit the success of therapy. Generation of reactive oxygen species (ROS) has been implicated for numerous chemotherapeutic agents including doxorubicin (DOX), a potent cancer chemotherapeutic drug. The production of ROS by DOX has been linked to DNA damage, nuclear translocation of p53, and mitochondrial injury; however, the causal relationship and molecular mechanisms underlying these events are unknown. The present study used wild-type (WT) and p53 homozygous knock-out (p53(-/-)) mice to investigate the role of p53 in the crosstalk between mitochondria and nucleus. Injecting mice with DOX (20 mg/kg) causes oxidative stress in cardiac tissue as demonstrated by immunogold analysis of the levels of 4-hydroxy-2'-nonenal (4HNE)-adducted protein, a lipid peroxidation product bound to proteins. 4HNE levels increased in both nuclei and mitochondria of WT DOX-treated mice but only in nuclei of DOX-treated p53((-/-)) mice, implicating a critical role for p53 in causing DOX-induced oxidative stress in mitochondria. The stress-activated protein c-Jun amino-terminal kinase (JNKs) was activated in response to increased 4HNE in WT mice but not p53((-/-)) mice receiving DOX treatment, as determined by co-immunoprecipitation of HNE and pJNK. The activation of JNK in DOX treated WT mice was accompanied by Bcl-2 dissociation from Beclin in mitochondria and induction of type II cell death (autophagic cell death), as evidenced by an increase in LC3-I/LC-3-II ratio and γ-H2AX, a biomarker for DNA damage. The absence of p53 significantly reduces mitochondrial injury, assessed by quantitative morphology, and decline in cardiac function, assessed by left ventricular ejection fraction and fraction shortening. These results demonstrate that p53 plays a critical role in DOX-induced cardiac toxicity, in part, by the induction of oxidative stress mediated retrograde signaling.