rss_2.0Asian Biomedicine FeedSciendo RSS Feed for Asian Biomedicine Biomedicine Feed acid: an attractive biomarker with promising biomedical applications<abstract> <title style='display:none'>Abstract</title> <p>This broad, narrative review highlights the roles of sialic acids as acidic sugars found on cellular membranes. The role of sialic acids in cellular communication and development has been well established. Recently, attention has turned to the fundamental role of sialic acids in many diseases, including viral infections, cardiovascular diseases, neurological disorders, diabetic nephropathy, and malignancies. Sialic acid may be a target for developing new drugs to treat various cancers and inflammatory processes. We recommend the routine measurement of serum sialic acid as a sensitive inflammatory marker in various diseases.</p> </abstract>ARTICLEtrue 85-amino-acid polypeptide from larvae (antlions) homologous to heat shock factor binding protein 1 with antiproliferative activity against MG-63 osteosarcoma cells in vitro<abstract> <title style='display:none'>Abstract</title> <sec><title style='display:none'>Background</title> <p>Venomous arthropods have substances in their venom with antiproliferative potential for neoplastic cells.</p> </sec> <sec><title style='display:none'>Objectives</title> <p>To identify a polypeptide from <italic>Myrmeleon bore</italic> (antlion) with antiproliferative activity against neoplastic cells, and to elucidate the molecular mechanism of the activity.</p> </sec> <sec><title style='display:none'>Methods</title> <p>We used gel filtration and ion exchange chromatography to purify a polypeptide with antiproliferative activity against MG-63 human osteosarcoma cells from a proteinaceous extract of antlion. The polypeptide was sequenced and the stability of its antiproliferative activity was tested under a range of conditions in vitro. An 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to determine the antiproliferative activity of the polypeptide against the MG-63 osteosarcoma cells and MC3T3-E1 mouse calvarial osteoblasts, which were used as a non-neoplastic control. We used western blotting to compare the levels of expression of heat shock transcription factor 1 (HSF1), heat shock protein 90 (HSP90), cyclin-dependent kinase 4 (CDK4), and protein kinase B alpha (ATK1) in MG-63 osteosarcoma cells and their mouse homologs in MC3T3-E1 osteoblasts after their treatment with the antlion antiproliferative polypeptide (ALAPP).</p> </sec> <sec><title style='display:none'>Results</title> <p>The 85-amino-acid ALAPP has a 56% sequence identity with the human heat shock factor binding protein 1 (HSBP1). The antiproliferative activity of the polypeptide is relatively insensitive to temperature, pH, and metal ions. ALAPP has a strong concentration-dependent antiproliferative activity against MG-63 osteosarcoma cells compared with its effect on MC3T3-E1 osteoblasts. ALAPP significantly upregulates the expression of HSF1 in MC3T3-EL osteoblasts, but not in MG-63 osteosarcoma. ALAPP significantly downregulated the expression of HSP90, CDK4, and AKT1 expression in MG-63 osteosarcoma, but not in the osteoblasts.</p> </sec> <sec><title style='display:none'>Conclusions</title> <p>ALAPP has significant antiproliferative activity against MG-63 osteosarcoma cells, but not nonneoplastic MC3T3-E1 osteoblasts. We speculate that non-neoplastic cells may evade the antiproliferative effect of ALAPP by upregulating HSF1 to maintain their HSP90, CDK4, and AKT1 expression at a relatively constant level.</p> </sec> </abstract>ARTICLEtrue resistance, biofilm forming ability, and clonal profiling of clinical isolates of from southern and northeastern India<abstract> <title style='display:none'>Abstract</title> <sec><title style='display:none'>Background</title> <p><italic>Staphylococcus aureus</italic> is a pathogen endemic in India and sometimes deadly for patients in intensive care units.</p> </sec> <sec><title style='display:none'>Objectives</title> <p>To determine the antibiotic-resistance pattern, biofilm forming ability, and clonal type of <italic>S. aureus</italic> from isolates collected in Tamil Nadu (south) and the Mizoram (northeast) regions of India.</p> </sec> <sec><title style='display:none'>Methods</title> <p>We collected <italic>S. aureus</italic> isolates from diagnostic laboratories in Tamil Nadu and Mizoram. An antibiotic susceptibility test was performed according to Clinical Laboratory and Standards Institute methods. Antibiotic-resistant determinants such as <italic>mecA</italic>, <italic>mecC</italic>, <italic>blaZ</italic>, <italic>vanA</italic>, <italic>vanB</italic>, and <italic>vanC</italic> were confirmed by polymerase chain reaction (PCR). All isolates were further studied for biofilm forming ability. Enterobacterial repetitive intergenic consensus (ERIC)-PCR was used for clonal analysis.</p> </sec> <sec><title style='display:none'>Results</title> <p>A study of 206 clinical isolates showed 52.9% prevalence of methicillin-resistant <italic>S. aureus</italic> in Tamil Nadu and 49.4% in Mizoram. Minimum inhibitory concentration tests showed a high prevalence of 67% oxacillin resistance in isolates from Tamil Nadu and 49% in isolates from Mizoram. PCR showed 53% <italic>mecA</italic> in Tamil Nadu and 49% <italic>mecA</italic> in Mizoram. Vancomycin-intermediate resistance <italic>S. aureus</italic> (VISA) prevalence was lower in isolates from Tamil Nadu (4%) and Mizoram (5%). All methicillin-resistant <italic>S. aureus</italic> (MRSA) isolates formed biofilms. Clonal analysis revealed a genetic relatedness between the isolates.</p> </sec> <sec><title style='display:none'>Conclusions</title> <p>The prevalence of MRSA is high in the regions studied, with most of the clinical isolates being multidrug resistant. Adopting appropriate community-based preventive measures and establishing antimicrobial stewardship is highly recommended to minimize the dissemination in antibiotic resistance.</p> </sec> </abstract>ARTICLEtrue One Health approach to antimicrobial resistance methylation analysis of may be a potential biomarker for early detection of cervical cancer<abstract> <title style='display:none'>Abstract</title> <sec><title style='display:none'>Background</title> <p>Dickkopf 2 (<italic>DKK2</italic>) plays an important role in multiple cancers. Its potential value in the clinical diagnosis of cervical cancer has remained unclear.</p> </sec> <sec><title style='display:none'>Objectives</title> <p>To investigate the expression and promoter methylation levels of <italic>DKK2</italic> in cervical cancer and their clinicopathological associations.</p> </sec> <sec><title style='display:none'>Methods</title> <p>We used the Gene Expression Omnibus, Oncomine, Cancer Genome Atlas, and University of ALabama at Birmingham CANcer data analysis databases, reverse transcription-PCR, and methylation-specific PCR analysis to predict and examine the expression of DKK2 mRNA and <italic>DKK2</italic> methylation levels in cell lines and cervical cancer tissues from 79 patients with cervical cancer and 63 with cervical precancerous lesions including 25 with low-grade squamous intraepithelial lesions (LSIL) and 38 patients with high-grade squamous intraepithelial lesions (HSIL).</p> </sec> <sec><title style='display:none'>Results</title> <p>DKK2 mRNA expression was downregulated in all cancer cell lines and cervical cancer tissues, whereas hypermethylation of <italic>DKK2</italic> was higher in cervical cancer tissue samples. <italic>DKK2</italic> methylation in cervical cancer was significantly higher than that in HSIL (χ<sup>2</sup> = 8.346, <italic>P</italic> = 0.004), whereas <italic>DKK2</italic> methylation in HSIL was significantly higher than that in normal cervical samples (χ<sup>2</sup> = 7.934, <italic>P</italic> = 0.005) and in LSIL samples (χ<sup>2</sup> = 4.375, <italic>P</italic> = 0.037). <italic>DKK2</italic> silencing caused by its promoter hypermethylation was confirmed by treatment with the methyltransferase inhibitor 5-Aza-dC in cell lines. Patients with lymph node metastasis exhibited increased promoter methylation frequency (χ<sup>2</sup> = 5.239, <italic>P</italic> = 0.022) and low DKK2 mRNA expression (χ<sup>2</sup> = 3.958, <italic>P</italic> = 0.047) compared with patients with no lymph node metastasis. Patients with high-risk human papillomavirus infection exhibited increased promoter methylation frequency (χ<sup>2</sup> = 6.279, <italic>P</italic> = 0.015).</p> </sec> <sec><title style='display:none'>Conclusions</title> <p><italic>DKK2</italic> epigenetic changes of DKK2 may play a key role in the development of cervical cancer, suggesting that <italic>DKK2</italic> hypermethylation could be used as a triage test for screening, early diagnosis, or risk prediction of cervical cancer.</p> </sec> </abstract>ARTICLEtrue noncoding and micro-RNA expression in a model of articular chondrocyte degeneration induced by stromal cell-derived factor-1<abstract> <title style='display:none'>Abstract</title> <sec><title style='display:none'>Background</title> <p>Gene regulatory network analysis has found that long noncoding ribonucleic acids (lncRNAs) are strongly associated with the pathogenesis of osteoarthritis.</p> </sec> <sec><title style='display:none'>Objectives</title> <p>To determine the differential expression of lncRNAs and microRNAs (miRNAs) in normal chondrocytes and those from a model of articular chondrocyte degeneration.</p> </sec> <sec><title style='display:none'>Methods</title> <p>Chondrocytes were cultured from cartilage obtained from patients diagnosed with osteoarthritis of the knee. Stromal cell-derived factor-1 (SDF-1) was used to induce their degeneration. Total RNA was extracted, analyzed, amplified, labeled, and hybridized on a chip to determine expression. The set of enriched differentially expressed miRNAs was analyzed by gene ontology and the Kyoto Encyclopedia of Genes and Genomes to describe the functional properties of the key biological processes and pathways. We conducted a bioinformatics analysis using Cytoscape to elucidate the interactions between miRNAs and proteins.</p> </sec> <sec><title style='display:none'>Results</title> <p>We found that the expression of 186 lncRNAs was significantly different in the model of chondrocyte degeneration, in which 88 lncRNAs were upregulated, and 98 were downregulated. Expression of 684 miRNAs was significantly different. Analysis of the protein–protein interaction (PPI) network indicated that the genes for CXCL10, ISG15, MYC, MX1, OASL, IFIT1, RSAD2, MX2, IFI44L, and BST2 are the top 10 core genes, identifying the most important functional modules to elucidate the differential expression of miRNAs.</p> </sec> <sec><title style='display:none'>Conclusions</title> <p>These data may provide new insights into the molecular mechanisms of chondrocyte degeneration in osteoarthritis, and the identification of lncRNAs and miRNAs may provide potential targets for the differential diagnosis and therapy of osteoarthritis.</p> </sec> </abstract>ARTICLEtrue and efficacy of non–vitamin K antagonist oral anticoagulants compared with well-controlled warfarin in Thai patients with atrial fibrillation<abstract> <title style='display:none'>Abstract</title> <sec><title style='display:none'>Background</title><p>In trials of patients with atrial fibrillation (AF), non–vitamin K antagonist oral anticoagulants (NOACs) were not inferior to warfarin for thromboembolic and bleeding events. However, there are scant data comparing the efficacy and safety of NOACs in patients with AF with that of well-controlled warfarin treatment in such patients.</p></sec> <sec><title style='display:none'>Objectives</title><p>To compare total bleeding and thromboembolic events in patients with AF who received NOACs, with the same events in those who received well-controlled warfarin treatment.</p></sec> <sec><title style='display:none'>Methods</title><p>We used retrospective data from patients with AF who received NOACs or well-controlled warfarin at the Central Chest Institute of Thailand from January 2017 to December 2019. The primary outcome was total bleeding or thromboembolic events or both. The secondary outcome was all-cause mortality, total bleeding events including major or minor bleeding, and thromboembolic events including ischemic stroke or systemic embolization.</p></sec> <sec><title style='display:none'>Results</title><p>We included data from 180 patients with AF, 90 who received NOACs and 90 who received well-controlled warfarin. The average time in the therapeutic range for those who received warfarin was 84.9% ± 9.8%. The patients who received well-controlled warfarin had more frequent thromboembolic or total bleeding events or both than those who received NOACs (odds ratio [OR] 3.17; 95% confidence interval [CI] 2.27–4.07; <italic>P</italic> = 0.01). There were more minor bleeding events in those who received well-controlled warfarin (OR 3.75; 95% CI 2.79–4.71; <italic>P</italic> = 0.01). However, there was no significant difference in thromboembolic events, major bleeding, or all-cause mortality between the 2 groups.</p></sec> <sec><title style='display:none'>Conclusions</title><p>Thai patients with AF who received NOACs had less thromboembolic or total bleeding events than those who received well-controlled warfarin treatment.</p></sec> </abstract>ARTICLEtrue tumor resembling ovarian sex-cord tumor: case report and review of the literature<abstract> <title style='display:none'>Abstract</title> <sec><title style='display:none'>Background</title><p>We report the clinicopathological characteristics, immunohistochemical features, ultrastructure, tissue source, differential diagnosis, treatment, and prognosis of a patient with a uterine tumor resembling ovarian sex-cord tumor (UTROSCT).</p></sec> <sec><title style='display:none'>Case report</title><p>A 40-year-old woman had a uterine myoma with enlargement for 2.5 years. An ultrasound examination showed a mixed echogenic mass at the posterior wall of the uterus and a dark cyst in the right adnexal area, which suggested a suspected uterine myoma with liquefaction and a suspected chocolate cyst. The patient underwent transabdominal tumor resection with removal of the right adnexal mass. Through postoperative pathological examination, the patient was diagnosed with UTROSCT. No recurrence was observed after a follow-up of 1 year.</p></sec> <sec><title style='display:none'>Conclusion</title><p>Although UTROSCT is usually benign, it can relapse or metastasize, and patients with UTROSCT need comprehensive diagnosis and treatment.</p></sec> </abstract>ARTICLEtrue collaborations are needed for mangrove land use and mosquito control shear wave elastography of the thyroid in patients with sickle cell anemia<abstract> <title style='display:none'>Abstract</title> <sec><title style='display:none'>Background</title><p>Although thyroid radiology has been conducted in patients with sickle cell anemia (SCA), to our knowledge, there is no report of thyroid gland assessment using ultrasonographic shear wave elastography (US-SWE).</p></sec> <sec><title style='display:none'>Objectives</title><p>To determine values for ultrasonographic US-SWE of the thyroid in patients with SCA and correlations between thyroid elasticity and biochemical variables used to evaluate thyroid function.</p></sec> <sec><title style='display:none'>Methods</title><p>Prospective case–control observational study of 36 patients with SCA and 33 healthy volunteer controls. US-SWE measurements of thyroid gland parenchyma and biochemical parameters of the participants were obtained and compared, and the diagnostic accuracy of elasticity was determined.</p></sec> <sec><title style='display:none'>Results</title><p>The thyroid volume was smaller in patients with SCA than that in controls (<italic>P</italic> = 0.001). Compared with the controls, the patients with SCA had significantly lower serum levels of free triiodothyronine (fT3) (<italic>P</italic> = 0.004) and thyroglobulin (Tg) (<italic>P</italic> = 0.001) and significantly higher levels of thyroid-stimulating hormone (<italic>P</italic> = 0.028). Thyroid stiffness was significantly higher in the left lobe (LL) of the patients with SCA than in the controls (<italic>P</italic> = 0.003). In the patients with SCA, we found a significant correlation between right lobe (RL) and LL stiffness and serum levels of Tg (RL [<italic>r</italic> = −0.439] and LL [<italic>r</italic> = −0.484]; <italic>P</italic> = 0.021) and fT3 (RL [<italic>r</italic> = −0.463] and LL [<italic>r</italic> = −0.386]; <italic>P</italic> = 0.012). Receiver operating characteristic (ROC) curve analysis of thyroid elasticity that represented a diagnosis of SCA found a cutoff of &gt;7.31 kPa, a sensitivity of 52.0%, and a specificity of 72.0% for the RL (<italic>P</italic> = 0.316, area under the curve [AUC] 0.570), and a cutoff of &gt;8.06 kPa, a sensitivity of 58.0%, and a specificity of 84.0% for the LL (<italic>P</italic> = 0.011, AUC 0.680).</p></sec> <sec><title style='display:none'>Conclusions</title><p>US-SWE can be used to follow up thyroid changes in patients with SCA.</p></sec> </abstract>ARTICLEtrue (Diptera: Culicidae) diversity and medical importance in Koh Kong mangrove forests, Cambodia<abstract> <title style='display:none'>Abstract</title> <sec><title style='display:none'>Background</title><p>Mangroves are an ecosystem interface between land and sea, forming distinctive shallow-water marine communities in tropical and subtropical waters. The mangrove forest surface in Cambodia is being reduced due to deforestation. Because the mangrove type of ecosystem generally hosts a great diversity of mosquitoes, the urbanization of these ecosystems will increase interactions between humans and wild mosquitoes, and might thus serve as a potential source of new infectious diseases. Understanding mosquito diversity and analyzing their virome is critical to estimate the risk of emergence or future outbreaks of mosquito-borne diseases.</p></sec> <sec><title style='display:none'>Objective</title><p>To understand the mosquito diversity of mangrove forests of Koh Kong province (Cambodia).</p></sec> <sec><title style='display:none'>Methods</title><p>In 2019, the mosquito fauna was sampled for 3 consecutive days using BG-Sentinel and light traps, in 3 locations in the mangrove forests of Koh Kong province (Cambodia) during both dry and rainy seasons.</p></sec> <sec><title style='display:none'>Results</title><p>A total of 3107 samples were collected, belonging to 10 genera for 34 species. The <italic>Culex</italic> genus was the most diverse, accounting for 10 species. One species, <italic>Culex sitiens,</italic> represented over 60% of all collected mosquitoes. A total of 12 medically important species were recorded, 2 species, <italic>Aedes</italic> (<italic>Stegomyia</italic>) <italic>albopictus</italic> and <italic>Culex vishnui</italic>, were collected in all sites and during both the dry and rainy seasons, highlighting a potential risk of these species acting as bridge vectors.</p></sec> <sec><title style='display:none'>Conclusions</title><p>If new arboviruses were to be recorded in this peculiar area, it would indicate that the mosquito species found have the potential to act as a bridge between sylvatic and anthropogenic arboviruses.</p></sec> </abstract>ARTICLEtrue role of autophagy in cancer<abstract> <title style='display:none'>Abstract</title> <p>Autophagy is an evolutionary conserved catabolic process that plays physiological and pathological roles in a cell. Its effect on cellular metabolism, the proteome, and the number and quality of organelles, diversely holds the potential to alter cellular functions. It acts paradoxically in cancer as a tumor inhibitor as well as a tumor promoter. In the early stage of tumorigenesis, it prevents tumor initiation by the so-called “quality control mechanism” and suppresses cancer progression. For late-staged tumors that are exposed to stress, it acts as a vibrant process of degradation and recycling that promotes cancer by facilitating metastasis. Despite this dichotomy, the crucial role of autophagy is evident in cancer, and associated with mammalian targets of rapamycin (mTOR), p53, and Ras-derived major cancer networks. Irrespective of the controversy regarding autophagic manipulation, promotion and suppression of autophagy act as potential therapeutic targets in cancer treatment and may provide various anticancer therapies.</p> </abstract>ARTICLEtrue impairment in the elderly: the need for a comprehensive approach levels of interleukin-34 and RANKL as multivariable predictors of bone erosion seen by ultrasonography in patients with ankylosing spondylitis<abstract> <title style='display:none'>Abstract</title> <sec><title style='display:none'>Background</title> <p>Ankylosing spondylitis (AS) is a chronic inflammatory arthritic disease, and sacroiliitis, enthesitis, and propensity for sacroiliac and spinal fusion are characteristic pathological features. Interleukin-34 (IL-34) plays a role in the induction and differentiation of osteoclasts. Other inflammatory factors are not directly involved in the induction and differentiation, but play an indirect role by modulating the level of receptor activator of nuclear factor-κB (RANKL) and other molecules during the process of inflammatory bone destruction in AS. However, to our knowledge, the relationship between enthesitis and bone erosion, and IL-34 and RANKL in AS has not yet been elucidated.</p> </sec> <sec><title style='display:none'>Objective</title> <p>To determine the correlation between serum IL-34, RANKL, and disease severity including enthesitis and bone erosion in patients with AS and develop multivariable predictive model.</p> </sec> <sec><title style='display:none'>Methods</title> <p>We conducted a cross-sectional study of 40 patients with AS, compared with 40 patients with osteoarthritis, and 40 healthy volunteers. Their serum levels of IL-34 and RANKL were measured using enzyme-linked immunosorbent assays (ELISAs). Enthesitis and bone erosion were assessed with real-time ultrasonography. Spearman rank correlation coefficients were determined to analyze the relationship between the variables. Multiple logistic regression was used to determine associations and receiver operating characteristic (ROC) curve analyses were conducted to determine the diagnostic performance of cytokine levels.</p> </sec> <sec><title style='display:none'>Results</title> <p>In patients with AS, serum levels of IL-34 (878.9 ± 116.4 pg/mL) and RANKL (155.6 ± 13.8 pg/mL) were significantly (<italic>P</italic> &lt; 0.01) higher than those in patients with osteoarthritis (626.6 ± 79.0 and 138.1 ± 15.3 pg/mL, respectively) or a healthy group (612.9 ± 61.1 and 104.9 ± 15.4 pg/mL, respectively). Serum levels of IL-34 were not significantly correlated with the levels of RANKL. In patients with AS, serum levels of IL-34 and RANKL adjusted for age and weight were significantly correlated with enthesitis (0.798, <italic>P</italic> &lt; 0.01; 0.347, <italic>P</italic> &lt; 0.05, respectively) and bone erosion (0.822, <italic>P</italic> &lt; 0.01; 0.368, <italic>P</italic> &lt; 0.05, respectively). The area under the ROC curve (AUC) for the serum levels of IL-34 was 0.995 between patients with AS and healthy individuals. When serum level of IL-34 was &gt;697.1 pg/mL, the sensitivity (SE) was &gt;99% and specificity (SP) was 95.0%. The AUC for IL-34 was 0.982 between patients with AS and patients with osteoarthritis. When serum IL-34 was &gt;688.4 pg/mL, the SE was &gt;99% and SP 85.0%. IL-34 correlation with the number of bone erosions of enthesis was <italic>r<sub>s</sub></italic> = 0.795, <italic>P</italic> &lt; 0.01. The AUC for serum RANKL was 0.993 between patients with AS and healthy individuals. When serum RANKL was &gt;126.2 pg/mL, the SE was 97.5% and SP 97.5%. The AUC for serum RANKL was 0.798 between patients with AS and patients with osteoarthritis. When serum RANKL was &gt;149.3 pg/mL, the SE was 70% and SP was 80.0%.</p> </sec> <sec><title style='display:none'>Conclusions</title> <p>In patients with AS, serum levels of IL-34 and RANKL may be useful indicators of enthesitis, especially for bone erosions. IL-34 is associated with AS-associated enthesis damage and is a potential biomarker for predicting subsequent progression in patients with AS.</p> </sec> </abstract>ARTICLEtrue receptor subtype-2B signaling is associated with interleukin-18-induced cardiomyoblast hypertrophy in vitro<abstract> <title style='display:none'>Abstract</title> <sec><title style='display:none'>Background</title> <p>In patients with heart failure, interleukin-18 (IL-18) levels increase in the circulatory system and injured myocardial tissue. Serotonin (5-hydroxytryptamine) receptors subtype 2B (HTR2B) play an essential role in cardiac function and development, and their overexpression in rats leads to myocardial hypertrophy. Epigallocatechin gallate (EGCG) is cardioprotective in myocardial ischemia–reperfusion injury in rats and can prevent pressure overload-mediated cardiac hypertrophy in vivo. Mice deficient in peroxisome proliferator-activated receptor delta (PPARδ) can have cardiac dysfunction, myocardial hypertrophy, and heart failure. Matrix metalloproteinases (MMPs) are possibly involved in cardiac remodeling. However, the relationship between IL-18 signaling, cardiac hypertrophy, and the molecular mechanisms involved remain to be fully elucidated.</p> </sec> <sec><title style='display:none'>Objectives</title> <p>To elucidate the relationship between HTR2B and IL-18-induced myocardial hypertrophy and examine the antihypertrophic effects of EGCG and PPARδ.</p> </sec> <sec><title style='display:none'>Methods</title> <p>We induced H9c2 cardiomyoblast hypertrophy with IL-18 in vitro and investigated the downstream signaling by real-time polymerase chain reaction (PCR) and western blotting. Hypertrophy was assessed by flow cytometry. We determined the effects of EGCG and PPARδ on IL-18-induced hypertrophic signaling via HTR2B-dependent mechanisms.</p> </sec> <sec><title style='display:none'>Results</title> <p>IL-18-induced H9c2 hypertrophy upregulated brain natriuretic peptide (BNP) protein and mRNA expression by inducing the expression of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), and the hypertrophy was attenuated by pretreatment with EGCG (20 μM) and L-165,041 (2 μM), a PPARδ agonist. IL-18 upregulated the expression of HTR2B, which was inhibited by pretreatment with EGCG and L-165,041. SB215505 (0.1 μM), a HTR2B antagonist and siRNA for HTR2B, attenuated H9c2 hypertrophy significantly. Inhibition of HTR2B also downregulated the expression of MMP-3 and MMP-9.</p> </sec> <sec><title style='display:none'>Conclusions</title> <p>IL-18 and HTR2B play critical roles in cardiomyoblast hypertrophy. EGCG and L-165,041 inhibit the expression of HTR2B and augment remodeling of H9c2 cardiomyoblasts, possibly mediated by MMP-3 and MMP-9.</p> </sec> </abstract>ARTICLEtrue fistula in a Thai boy with c.101A>G substitution variant-related chronic pancreatitis: a case report and literature review<abstract> <title style='display:none'>Abstract</title> <sec><title style='display:none'>Background</title> <p>Chronic pancreatitis is the most common etiology of pancreaticopleural fistula (PPF) in children, and underlying genetic variations are now widely known, accounting for most chronic pediatric pancreatitis.</p> </sec> <sec><title style='display:none'>Case report</title> <p>We describe a case of previously undetected chronic pancreatitis and PPF with a <italic>SPINK1</italic> variation in a 10-year-old Thai boy who presented with massive left pleural effusion. Magnetic resonance cholangiopancreatography (MRCP) revealed disruption of the pancreatic duct, which was communicating with a large pancreatic pseudocyst with mediastinal extension. The patient subsequently underwent endoscopic intervention with improved clinical symptoms. We also reviewed the imaging findings of 12 other reported cases of pediatric PPF.</p> </sec> <sec><title style='display:none'>Conclusions</title> <p>Massive pleural effusion due to PPF can be an atypical manifestation in children with chronic pancreatitis. MRCP is the preferable imaging study for PPF due to the production of highly detailed images of pancreatic duct disruptions and anatomy, and the imaging is helpful to guide for appropriate treatment. Tests for genetic variation are also recommended in a child with chronic pancreatitis.</p> </sec> </abstract>ARTICLEtrue reduces alloxan-induced impairment of aversive stimulus memory in mice<abstract> <title style='display:none'>Abstract</title> <sec><title style='display:none'>Background</title> <p>An association between dysregulated glucose levels in patients with diabetes mellitus and detrimental effects on the central nervous system, particularly in Alzheimer disease, has been recognized. Atorvastatin treatment has improved memory and cognition in some patients with diabetes mellitus and Alzheimer disease.</p> </sec> <sec><title style='display:none'>Objectives</title> <p>To determine possible neuroprotective effects of atorvastatin on memory and cognition by measuring changes in an adverse stimulus avoidance learning deficit induced by alloxan in a murine model of diabetes mellitus and impaired memory and cognition.</p> </sec> <sec><title style='display:none'>Methods</title> <p>We administered 150 mg/kg and 100 mg/kg alloxan in saline (intraperitoneally, i.p.) at a 48 h interval to produce a model of diabetes mellitus in male BALB/c mice. An oral glucose tolerance test (OGTT) was used to assess blood glucose regulation. After demonstrating hyperglycemia in mice (n = 7 per group) we administered vehicle (saline, i.p.), atorvastatin (10 mg/kg, i.p.), or liraglutide (200 μg/kg, i.p.) for 28 d except for those in a negative control group, which were given saline instead of alloxan, and a group administered atorvastatin alone, which were given saline instead of alloxan followed by atorvastatin (10 mg/kg, i.p.) for 28 d. Locomotor activity was measured 24 h after the final drug treatments, and subsequently their learned behavioral response to an adverse electrical stimulus to their plantar paw surface in a dark compartment was measured using a passive avoidance apparatus (Ugo Basile) in a model of impaired memory and cognition associated with Alzheimer disease. To determine any deficit in their learned avoidance of the adverse stimulus, we measured the initial latency or time mice spent in an illuminated white compartment before entering the dark compartment in the learning trial, and on the day after learning to avoid the adverse stimulus, the retention period latency in the light compartment and time spent in the dark compartment.</p> </sec> <sec><title style='display:none'>Results</title> <p>Atorvastatin alone produced no significant change in blood glucose levels (<italic>F</italic><sub>4,10</sub> = 0.80, <italic>P</italic> = 0.55) within 2 h. Liraglutide decreased blood glucose levels after 0.5 h (<italic>F</italic><sub>4,10</sub> = 11.7, <italic>P</italic> &lt; 0.001). We found no significant change in locomotor activity in any group. In mice with alloxan-induced diabetes, atorvastatin significantly attenuated the decreased avoidance associated with the diabetes (<italic>F</italic><sub>4,30</sub> = 38.0, <italic>P</italic> = 0.02) and liraglutide also significantly attenuated the decreased avoidance (<italic>F</italic><sub>4,30</sub> = 38.0, <italic>P</italic> &lt; 0.001). Atorvastatin alone had no significant effect on the adversive learned response compared with vehicle treatment (<italic>F</italic><sub>4,30</sub> = 38.0, <italic>P</italic> &gt; 0.05). Atorvastatin significantly decreased the time mice with alloxan-induced diabetes spent in the dark compartment compared with mice in the diabetes group without atorvastatin treatment (<italic>F</italic><sub>4,30</sub> = 53.9, <italic>P</italic> = 0.046). Liraglutide also significantly reduced the time mice with alloxan-induced diabetes spent in the dark compartment compared with vehicle-treated mice with alloxan-induced diabetes (<italic>F</italic><sub>4,30</sub> = 53.9, <italic>P</italic> &lt; 0.001). Atorvastatin treatment alone had no significant effect on the time mice spent in dark compartment compared with the control group (<italic>F</italic><sub>4,30</sub> = 53.9, <italic>P</italic> &gt; 0.05).</p> </sec> <sec><title style='display:none'>Conclusion</title> <p>Atorvastatin significantly attenuated the adverse stimulus avoidance learning deficit in the alloxan-induced murine model of diabetes suggesting decreased impairment of memory and cognition.</p> </sec> </abstract>ARTICLEtrue of antidepressive drugs: an overview of stereoselectivity<abstract> <title style='display:none'>Abstract</title> <p>Stereochemistry plays an important role in drug design because the enantiomers of a drug frequently vary in their biological action and pharmacokinetic profiles. Racemates of a drug with either an inactive or an unsafe enantiomer can lead to detrimental effects. The manufacturing industry may still produce racemates, but such decisions must pass through rigorous analyses of the pharmacological and pharmacokinetic characteristics of the particular enantiomer related to the racemates. The pharmacokinetics of antidepressants or antidepressive agents is stereoselective and predominantly favors one enantiomer. The use of pure enantiomers offers (i) better specificity than the racemates in terms of certain pharmacological actions, (ii) enhanced clinical indications, and (iii) optimized pharmacokinetics. Therefore, controlling the stereoselectivity in the pharmacokinetics of antidepressive drugs is of critical importance in dealing with depression and psychiatric conditions. The objective of this review is to highlight the importance of the stereochemistry of antidepressants in the context of the design and development of new chirally pure pharmaceuticals, the potential complications caused by using racemates, and the benefits of using pure enantiomers.</p> </abstract>ARTICLEtrue accuracy of complete blood cell count and neutrophil-to-lymphocyte, lymphocyte-to-monocyte, and platelet-to-lymphocyte ratios for neonatal infection<abstract> <title style='display:none'>Abstract</title> <sec><title style='display:none'>Background</title> <p>Complete blood cell (CBC) counts and neutrophil-to-lymphocyte (NLR), lymphocyte-to-monocyte (LMR), and platelet-to-lymphocyte ratios (PLR) are simple measurements that are conducted as part of routine diagnostic procedures.</p> </sec> <sec><title style='display:none'>Objective</title> <p>To determine the diagnostic importance, specificity, and sensitivity of these measurements for the diagnosis of neonatal infections and in discriminating between neonatal sepsis and various other infections.</p> </sec> <sec><title style='display:none'>Methods</title> <p>We conducted a retrospective study of data from a consecutive series of 232 neonatal patients admitted to Yildirim Beyazit University Yenimahalle Training and Research Hospital in Ankara for 2 years from 2016 to 2018. We included patients with a diagnosis of or clinically suspected infection, and healthy neonates were included as controls. Data included CBC counts, and bacterial culture results, considered the criterion standard for the diagnosis of neonatal sepsis. NLR, LMR, and PLR were calculated. We compared data using independent Student <italic>t</italic> and Mann–Whitney <italic>U</italic> tests and determined the sensitivity, specificity, and likelihood ratio (LHOR) of the characteristics for neonatal sepsis using receiver operating characteristic curve analyses.</p> </sec> <sec><title style='display:none'>Results</title> <p>We included data from 155 neonatal patients with a diagnosis or suspicion of infection and 77 healthy neonates. NLR was significantly higher in neonates with sepsis or fever due to dehydration (<italic>P</italic> &lt; 0.001) than in neonates with other infections or healthy neonates. LMR was significantly higher in neonates with sepsis or viral infection than in those with other infections or healthy controls (<italic>P</italic> = 0.003). In neonates with early-onset sepsis (EOS), we found cut-off values of ≥4.79 [area under curve (AUC) 0.845, 95% confidence interval (CI) 0.76–0.93, LHOR 11.6, specificity 98.7%, sensitivity 15%] for NLR, ≥1.24 (AUC 0.295; CI 0.18–0.41, LHOR 1.02, specificity 2.6%, sensitivity 100%) for LMR, and ≥37.72 (AUC 0.268; CI 0.15–0.39, LHOR 0.86, specificity 7.8%, sensitivity 80%) for PLR. We found cut-off values of ≥4.94 (AUC 0.667; CI 0.56–0.77, LHOR 4.16, specificity 98.7%, sensitivity 5.4%) for NLR and ≥10.92 (AUC 0.384; CI 0.26–0.51, LHOR 6.24, specificity 98.7%, sensitivity 8.1%) for LMR in those with late-onset sepsis (LOS).</p> </sec> <sec><title style='display:none'>Conclusions</title> <p>CBCs, NLR, LMR, and PLR may be useful for the differential diagnosis of EOS and LOS, and neonates with sepsis from those with other infection. NLR may be a useful diagnostic test to identify neonatal patients with septicemia more quickly than other commonly used diagnostic tests such as blood cultures. NLR has high specificity and LHOR, but low sensitivity.</p> </sec> </abstract>ARTICLEtrue RNA (piRNA): a narrative review of its biogenesis, function, and emerging role in lung cancer<abstract> <title style='display:none'>Abstract</title> <p>Cancer remains elusive in many aspects, especially in its causes and control. After protein profiling, genetic screening, and mutation studies, scientists now have turned their attention to epigenetic modulation. This new arena has brought to light the world of noncoding RNA (ncRNA). Although very complicated and often confusing, ncRNA domains are now among the most attractive molecular markers for epigenetic control of cancer. Long ncRNA and microRNA (miRNA) have been studied best among the noncoding genome and huge data have accumulated regarding their inhibitory and promoting effects in cancer. Another sector of ncRNAs is the world of PIWI-interacting RNAs (piRNAs). Initially discovered with the asymmetric division of germline stem cells in the <italic>Drosophila</italic> ovary, piRNAs have a unique capability to associate with mammalian proteins analogous to P-element induced wimpy testis (PIWI) in <italic>Drosophila</italic> and are capable of silencing transposons. After a brief introduction to its discovery timelines, the present narrative review covers the biogenesis, function, and role of piRNAs in lung cancer. The effects on lung cancer are highlighted under sections of cell proliferation, stemness maintenance, metastasis, and overall survival, and the review concludes with a discussion of recent discoveries of another class of small ncRNAs, the piRNA-like RNAs (piR-Ls).</p> </abstract>ARTICLEtrue