P2Y1 agonist HIC in combination with androgen receptor inhibitor abiraterone acetate impairs cell growth of prostate cancer.

P2Y receptors belong to the large superfamily of G-protein-coupled receptors and play a crucial role in cell death and survival. P2Y1 receptor has been identified as a marker for prostate cancer (PCa). A previously unveiled selective P2Y1 receptor agonist, the indoline-derived HIC (1-(1-((2-hydroxy-5-nitrophenyl)(4-hydroxyphenyl)methyl)indoline-4-carbonitrile), induces a series of molecular and biological responses in PCa cells PC3 and DU145, but minimal toxicity to normal cells. Here, we evaluated the combinatorial effect of HIC with abiraterone acetate (AA) targeted on androgen receptor (AR) on the inhibition of PCa cells. Here, the presence of HIC and AA significantly inhibited cell proliferation of PC3 and DU145 cells with time-dependent manner as a synerfistic combination. Moreover, it was also shown that the anticancer and antimetastasis effects of the combinratorial drugs were noticed through a decrease in colony-forming ability, cell migration, and cell invasion. In addition, the HIC + AA induced apoptotic population of PCa cells as well as cell cycle arrest in G1 progression phase. In summary, these studies show that the combination of P2Y1 receptor agonist, HIC and AR inhibitor, AA, effectively improved the antitumor activity of each drug. Thus, the combinatorial model of HIC and AA should be a novel and promising therapeutic strategy for treating prostate cancer.

Mutational screening of germline RB1 gene in Vietnamese patients with retinoblastoma reveals three novel mutations.

Purpose: Retinoblastoma (Rb) is a rare and unique eye cancer that usually develops in the retinas of children less than 5 years old due to mutations in the RB1 gene. About 40% of affected individuals have the heritable form making genetics testing of the RB1 gene important for disease management. This study aims to identify germline mutations in RB1 in a cohort of patients with Rb from northern Vietnam. Methods: Genomic DNA was extracted from peripheral blood of 34 patients with Rb (nine unilateral and 25 bilateral cases) and their available parents. Twenty-seven exons, flanking sequences, and the promoter region of RB1 gene were screened for mutations with direct PCR sequencing. Multiplex ligation-dependent probe amplification (MLPA) was applied for patients with negative sequencing results. In the mutation-positive patients, their available parental DNA was analyzed to determine the parental origin of the mutation. Results: Germline mutations in RB1 were identified in 25 (73.53%) of 34 patients (four unilateral and 21 bilateral cases). Of these mutations, 19 were detected, including seven nonsense, six frameshift, four splice-site (one was identified in two siblings), and one missense, with Sanger sequencing. Three novel frameshift mutations were discovered in one unilateral and two bilateral patients. MLPA detected mutations in the RB1 gene in six bilateral cases, of whom five had a whole gene deletion (three familial cases) and one had a partial gene deletion (from exon 4 to exon 27) in one allele of the RB1 gene. Parental testing showed five mutations originated from the fathers and one was inherited from a mother who was mosaic for the mutation. Conclusions: This study provides a data set of germline mutations in the RB1 gene in Vietnamese patients with retinoblastoma. Screening of mutations in the RB1 gene can help to identify heritable Rb and contribute to clinical management and genetic counseling for affected families.

A new polyoxygenated cyclohexene and a new megastigmane glycoside from Uvaria grandiflora.

A new polyoxygenated cyclohexene, (-)-3-O-debenzoylzeylenone (1), and a new megastigmane glycoside, grandionoside A (2), were isolated from the aerial parts of Uvaria grandiflora collected in Vietnam, together with ten known compounds including polyoxygenated cyclohexenes (3-6), a triterpenoid (7), an alkaloid (8), a long chain alcohol (9), hexenyl glycopyranoside (10), and saponins (11-12). Their chemical structures were elucidated by a combination of extensive NMR spectroscopy with X-ray crystallographic analysis for 1, and chemical conversion for 2. Compound 1 exhibited significant cytotoxicity against the LU-1 and SK-Mel-2 cell lines with IC50 values of 4.68 and 3.63 µM, respectively. Remarkably, the cytotoxicity of 12 against the LU-1, KB, Hep-G2, MKN-7, and SW-480 cell lines was comparable to that of ellipticine, the positive control, with IC50 values ranging from 1.24 to 1.60 µM.

The development and technologies of RNA therapeutics.

Since it was discovered for over 20 years ago, the potentiality of siRNAs in gene silencing in vitro and in vivo models has been recognized. Several studies in the new generation, molecular mechanisms, target attachment, and purification of RNA have supported the development of RNA therapeutics for a variety of applications. RNA therapeutics are growing rapidly with various platforms contributing to the standard of personalized medicine and rare disease treatment. Therefore, understanding the development and technologies of RNA therapeutics becomes a crucial point for new drug generation. Here, the primary purpose of this review is to provide a general view of six therapeutic categories that make up RNA-based therapeutic approaches, including RNA-target therapeutics, protein-targeted therapeutics, cellular reprogramming and tissues engineering, RNA-based protein replacement therapeutics, RNA-based genome editing, and RNA-based immunotherapies based on non-coding RNAs and coding RNA. Furthermore, we present an overview of the RNA strategies regarding viral approaches and nonviral approaches in designing a new generation of RNA technologies. The advantages and challenges of using RNA therapeutics are also discussed along with various approaches for RNA delivery. Therefore, this review is designed to provide updated reference evidence of RNA therapeutics in the battle against rare or difficult-to-treat diseases for researchers in this field.

Diagnostic value of vietnamese smell identification test in Parkinson's disease.

INTRODUCTION: The Vietnamese Smell Identification Test (VSIT) has been validated in determining olfactory dysfunction in the Vietnamese population; however, its value in diagnosing Parkinson's disease (PD) has not been established. METHODS: This case-control study was conducted at University Medical Center HCMC, Ho Chi Minh City, Vietnam. The study sample included non-demented PD patients and healthy controls (HC) who were gender- and age-matched. All participants were evaluated for odor identification ability using the VSIT and the Brief Smell Identification Test (BSIT). RESULTS: A total of 218 HCs and 218 PD patients participated in the study. The median VSIT and BSIT scores were significantly different between PD and HC groups (VSIT, 5 (3) vs. 9 (2), P < 0.0001; BSIT, 6 (3) vs 8 (2), P < 0.0001). Using the cut-off of <8 for correct answers out of 12 odorants, the VSIT had higher sensitivity (84.4%) and specificity (86.2%) than those of the BSIT (sensitivity of 81.7% and specificity of 69.3%) for the diagnosis of PD. The area under the curve (AUC) value was greater for the VSIT than for the BSIT (0.909 vs 0.818). The smell identification scores were not significantly correlated with disease duration, disease severity, or LEDD (all p > 0.05). CONCLUSION: The VSIT can be a valuable ancillary tool for supporting the diagnosis of PD in Vietnam. Olfactory dysfunction in PD was unrelated to the disease duration and severity. The VSIT can be applied to improve the accuracy of clinical PD diagnosis.

Normative data for the Vietnamese smell identification test.

Introduction: The 12-item Vietnamese smell identification test (VSIT) has been developed to evaluate the olfactory function of the Vietnamese population. This study aimed to investigate the normative value of the VSIT in different age groups and sexes. Methods: This cross-sectional study was conducted at Ho Chi Minh University Medical Center, Vietnam. All participants were evaluated for odor identification ability using the VSIT. We included healthy participants aged 18 years or older with no history of olfactory disturbances. Results: A total of 391 healthy volunteers were recruited with a mean age of 45.80 years (SD: 17.62; range: 18-86; female: 63.4 %). The tenth percentile of scores on the 0-12 VSIT scale was 8.3 in participants aged 18-29 years, 9.0 in 30-39 years, 8.0 in 40-49 years, 7.8 in 50-59 years, 7.9 in 60-69 years and 6.0 in over 70 years. Young adults (18-39 years old) had better olfactory identification ability than older adults (over 50 years), p < 0.001. There was a significant main effect of sex on VSIT score (p = 0.02), suggesting that females outperformed males. Sensitivity to 8 odors were negatively correlated with age: lemon, garlic, banana, coffee, mango, guava, apple and watermelon (p < 0.05 in all cases) whereas four odors were age-independent including orange, fish sauce, soy sauce, and fish. Conclusion: Normative data provide guidance for assessing individual olfactory function. However, there were significant sex and age effects on olfactory identification scores on the VSIT. Therefore, future studies should be conducted to better adjust for those confounders mentioned above.

Phosphorylation of EIF2S1 (eukaryotic translation initiation factor 2 subunit alpha) is indispensable for nuclear translocation of TFEB and TFE3 during ER stress.

There are diverse links between macroautophagy/autophagy pathways and unfolded protein response (UPR) pathways under endoplasmic reticulum (ER) stress conditions to restore ER homeostasis. Phosphorylation of EIF2S1/eIF2α is an important mechanism that can regulate all three UPR pathways through transcriptional and translational reprogramming to maintain cellular homeostasis and overcome cellular stresses. In this study, to investigate the roles of EIF2S1 phosphorylation in regulation of autophagy during ER stress, we used EIF2S1 phosphorylation-deficient (A/A) cells in which residue 51 was mutated from serine to alanine. A/A cells exhibited defects in several steps of autophagic processes (such as autophagosome and autolysosome formation) that are regulated by the transcriptional activities of the autophagy master transcription factors TFEB and TFE3 under ER stress conditions. EIF2S1 phosphorylation was required for nuclear translocation of TFEB and TFE3 during ER stress. In addition, EIF2AK3/PERK, PPP3/calcineurin-mediated dephosphorylation of TFEB and TFE3, and YWHA/14-3-3 dissociation were required for their nuclear translocation, but were insufficient to induce their nuclear retention during ER stress. Overexpression of the activated ATF6/ATF6α form, XBP1s, and ATF4 differentially rescued defects of TFEB and TFE3 nuclear translocation in A/A cells during ER stress. Consequently, overexpression of the activated ATF6 or TFEB form more efficiently rescued autophagic defects, although XBP1s and ATF4 also displayed an ability to restore autophagy in A/A cells during ER stress. Our results suggest that EIF2S1 phosphorylation is important for autophagy and UPR pathways, to restore ER homeostasis and reveal how EIF2S1 phosphorylation connects UPR pathways to autophagy.Abbreviations: A/A: EIF2S1 phosphorylation-deficient; ACTB: actin beta; Ad-: adenovirus-; ATF6: activating transcription factor 6; ATZ: SERPINA1/α1-antitrypsin with an E342K (Z) mutation; Baf A1: bafilomycin A1; BSA: bovine serum albumin; CDK4: cyclin dependent kinase 4; CDK6: cyclin dependent kinase 6; CHX: cycloheximide; CLEAR: coordinated lysosomal expression and regulation; Co-IP: coimmunoprecipitation; CTSB: cathepsin B; CTSD: cathepsin D; CTSL: cathepsin L; DAPI: 4',6-diamidino-2-phenylindole dihydrochloride; DMEM: Dulbecco's modified Eagle's medium; DMSO: dimethyl sulfoxide; DTT: dithiothreitol; EBSS: Earle's Balanced Salt Solution; EGFP: enhanced green fluorescent protein; EIF2S1/eIF2α: eukaryotic translation initiation factor 2 subunit alpha; EIF2AK3/PERK: eukaryotic translation initiation factor 2 alpha kinase 3; ER: endoplasmic reticulum; ERAD: endoplasmic reticulum-associated degradation; ERN1/IRE1α: endoplasmic reticulum to nucleus signaling 1; FBS: fetal bovine serum; gRNA: guide RNA; GSK3B/GSK3ß: glycogen synthase kinase 3 beta; HA: hemagglutinin; Hep: immortalized hepatocyte; IF: immunofluorescence; IRES: internal ribosome entry site; KO: knockout; LAMP1: lysosomal associated membrane protein 1; LMB: leptomycin B; LPS: lipopolysaccharide; MAP1LC3A/B/LC3A/B: microtubule associated protein 1 light chain 3 alpha/beta; MAP1LC3B/LC3B: microtubule associated protein 1 light chain 3 beta; MEFs: mouse embryonic fibroblasts; MFI: mean fluorescence intensity; MTORC1: mechanistic target of rapamycin kinase complex 1; NES: nuclear export signal; NFE2L2/NRF2: NFE2 like bZIP transcription factor 2; OE: overexpression; PBS: phosphate-buffered saline; PLA: proximity ligation assay; PPP3/calcineurin: protein phosphatase 3; PTM: post-translational modification; SDS: sodium dodecyl sulfate; SDS-PAGE: sodium dodecyl sulfate-polyacrylamide gel electrophoresis; SEM: standard error of the mean; TEM: transmission electron microscopy; TFE3: transcription factor E3; TFEB: transcription factor EB; TFs: transcription factors; Tg: thapsigargin; Tm: tunicamycin; UPR: unfolded protein response; WB: western blot; WT: wild-type; Xbp1s: spliced Xbp1; XPO1/CRM1: exportin 1.

Development and validation of the Vietnamese smell identification test.

BACKGROUND: Correct olfactory identification requires familiarity with the odor stimuli and is culturally dependent. Existing smell identification tests (SIT) are not culturally specific and may not be reliable in detecting hyposmia in all populations. This study aimed to develop a smell identification test suitable for Vietnamese patients (VSIT). METHODS: The study included 4 phases: 1) survey-based evaluation of the familiarity of 68 odors to identify 18 odors for subsequent testing (N = 1050); 2) smell identification test of 18 odors in healthy patients (N = 50) to determine which 12 should be included in the VSIT; 3) comparison of VSIT scores on 12 odors in patients with hyposmia (N = 60; Brief smell identification test (BSIT) score <8 and those with normosmia (N = 120; BSIT score ≥8) to establish the validity of the newly developed test; and 4) retest of the VSIT in 60 normosmic patients from phase 3 (N = 60) to determine test-retest reliability. RESULTS: As expected, the mean (SD) VSIT score was significantly higher in the healthy participants than in the hyposmic patients [10.28 (1.34) vs 4.57 (1.76); P < 0.001]. Using a cut-off score at 8, the sensitivity and specificity of the instrument in detecting hyposmia were 93.3% and 97.5% respectively. The test-retest reliability using the intra-class correlation coefficient was at 0.72 (P < 0.001). CONCLUSION: The Vietnamese Smell Identification Test (VSIT) demonstrated favorable validity and reliability and will allow for assessment of olfactory function in Vietnamese patients.

Machine Learning Heuristics on Gingivobuccal Cancer Gene Datasets Reveals Key Candidate Attributes for Prognosis.

Delayed cancer detection is one of the common causes of poor prognosis in the case of many cancers, including cancers of the oral cavity. Despite the improvement and development of new and efficient gene therapy treatments, very little has been carried out to algorithmically assess the impedance of these carcinomas. In this work, from attributes or NCBI's oral cancer datasets, viz. (i) name, (ii) gene(s), (iii) protein change, (iv) condition(s), clinical significance (last reviewed). We sought to train the number of instances emerging from them. Further, we attempt to annotate viable attributes in oral cancer gene datasets for the identification of gingivobuccal cancer (GBC). We further apply supervised and unsupervised machine learning methods to the gene datasets, revealing key candidate attributes for GBC prognosis. Our work highlights the importance of automated identification of key genes responsible for GBC that could perhaps be easily replicated in other forms of oral cancer detection.

Target Capture Reveals the Complex Origin of Vietnamese Ginseng.

The global market of the medicinal plant ginseng is worth billions of dollars. Many ginseng species are threatened in the wild and effective sustainable development initiatives are necessary to preserve biodiversity at species and genetic level whilst meeting the demand for medicinal produce. This is also the case of Panax vietnamensis Ha & Grushv., an endemic and threatened ginseng species in Vietnam that is locally cultivated at different scales and has been the object of national breeding programs. To investigate the genetic diversity within cultivated and wild populations of P. vietnamensis we captured 353 nuclear markers using the Angiosperm-353 probe set. Genetic diversity and population structure were evaluated for 319 individuals of Vietnamese ginseng across its area of distribution and from wild and a varying range of cultivated areas. In total, 319 individuals were sampled. After filtering, 1,181 SNPs were recovered. From the population statistics, we observe high genetic diversity and high genetic flow between populations. This is also supported by the STRUCTURE analysis. The intense gene flow between populations and very low genetic differentiation is observed regardless of the populations' wild or cultivated status. High levels of admixture from two ancestral populations exist in both wild and cultivated samples. The high gene flow between populations can be attributed to ancient and on-going practices of cultivation, which exist in a continuum from understorey, untended breeding to irrigated farm cultivation and to trade and exchange activities. These results highlight the importance of partnering with indigenous peoples and local communities and taking their knowledge into account for biodiversity conservation and sustainable development of plants of high cultural value.

Insights into the gene and protein structures of the CaSWEET family members in chickpea (Cicer arietinum), and their gene expression patterns in different organs under various stress and abscisic acid treatments.

'Sugars Will Eventually be Exported Transporters' (SWEETs) are a group of sugar transporters that play crucial roles in various biological processes, particularly plant stress responses. However, no information is available yet for the CaSWEET family in chickpea. Here, we identified all putative CaSWEET members in chickpea, and obtained their major characteristics, including physicochemical patterns, chromosomal distribution, subcellular localization, gene organization, conserved motifs and three-dimensional protein structures. Subsequently, we explored available transcriptome data to compare spatiotemporal transcript abundance of CaSWEET genes in various major organs. Finally, we studied the changes in their transcript levels in leaves and/or roots following dehydration and exogenous abscisic acid treatments using RT-qPCR to obtain valuable information underlying their potential roles in chickpea responses to water-stress conditions. Our results provide the first insights into the characteristics of the CaSWEET family members and a foundation for further functional characterizations of selected candidate genes for genetic engineering of chickpea.

Inappropriate supply of antibiotics for common viral infections by community pharmacies in Vietnam: A standardised patient survey.

Background: This study aimed to evaluate the appropriateness of antibiotic dispensing of private pharmacies in Vietnam. Methods: Standardised patient surveys were conducted in randomly selected community pharmacies across 40 districts in Vietnam. Four clinical scenarios were represented by patient actors: (a) an adult requesting treatment for a sibling with a viral upper respiratory tract infection (URTI), (b) a parent requesting treatment for a child with acute diarrhoea, (c) an adult making a direct antibiotic request, and (d) an adult presenting with an antibiotic prescription. We calculated the proportion of interactions that resulted in inappropriate supply of antibiotics and patient advice. Predictors of inappropriate antibiotic supply were assessed. Findings: Patient actors attended 949 pharmacies, resulting in 1266 clinical interactions. Antibiotics were inappropriately supplied to 92% (291/316) of adults requesting treatment for URTI symptoms, 43% (135/316) for children with acute diarrhoea symptoms and to 84% (267/317) of direct request for antibiotics. Only 49% of pharmacies advised patients regarding their antibiotic use. Female actors were more likely to be given antibiotics than male actors for URTI (aOR 2·71, 1·12-6·60) but not for diarrhoeal disease. Pharmacies in northern Vietnam were more likely than those in southern Vietnam to supply antibiotics without a prescription: for adult URTI (aOR=5·8, 95% CI: 2·2-14·9) and childhood diarrhoea (aOR=3·5, 95% CI: 2·0-6·0) symptoms, but less likely to dispense for direct antibiotics request. Interpretation: Inappropriate antibiotic supply was common in Vietnamese private pharmacies. Multifaceted measures are urgently needed to achieve WHO's global action plan for the optimal use of antimicrobials. Funding: This study was funded by a grant from the Australian Department of Foreign Affairs and Trade.

Functional characterization of HIC, a P2Y1 agonist, as a p53 stabilizer for prostate cancer cell death induction.

Background: (1-(2-hydroxy-5-nitrophenyl)(4-hydroxyphenyl)methyl)indoline-4-carbonitrile (HIC), an agonist of the P2Y1 receptor (P2Y1R), induces cell death in prostate cancer cells. However, the molecular mechanism behind the inhibition of HIC in prostate cancer remains elusive. Methods & results: Here, to outline the inhibitory role of HIC on prostate cancer cells, PC-3 and DU145 cell lines were treated with the respective IC50 concentrations, which reduced cell proliferation, adherence properties and spheroid formation. HIC was able to arrest the cell cycle at G1/S phase and also induced apoptosis and DNA damage, validated by gene expression profiling. HIC inhibited the prostate cancer cells' migration and invasion, revealing its antimetastatic ability. P2Y1R-targeted HIC affects p53, MAPK and NF-κB protein expression, thereby improving the p53 stabilization essential for G1/S arrest and cell death. Conclusion: These findings provide an insight on the potential use of HIC, which remains the mainstay treatment for prostate cancer.

Molecular interaction of HIC, an agonist of P2Y1 receptor, and its role in prostate cancer apoptosis.

Prostate cancer is a heterogeneous, slow growing asymptomatic cancer that predominantly affects man. A purinergic G-protein coupled receptor, P2Y1R, is targeted for its therapeutic value since it plays a crucial role in many key molecular events of cancer progression and invasion. Our previous study demonstrated that indoline derivative, 1 ((1-(2-Hydroxy-5-nitrophenyl) (4-hydroxyphenyl) methyl)indoline-4­carbonitrile; HIC), stimulates prostate cancer cell (PCa) growth inhibition via P2Y1R. However, the mode of interaction of P2Y1R with HIC involved in this process remains unclear. Here, we have reported the molecular interactions of HIC with P2Y1R. Molecular dynamics simulation was performed that revealed the stable specific binding of the protein-ligand complex. In vitro analysis has shown increased apoptosis of PCa-cells, PC3, and DU145, upon specific interaction of P2Y1R-HIC. This was further validated using siRNA analysis that showed a higher percentage of apoptotic cells in PCa-cells transfected with P2Y-siRNA-MRS2365 than P2Y-siRNA-HIC treatment. Decreased mitochondrial membrane potential (MMP) activity and reduced glutathione (GSH) level show their role in P2Y1R-HIC mediated apoptosis. These in silico and in vitro results confirmed that HIC could induce mitochondrial apoptotic signaling through the P2Y1R activation. Thus, HIC being a potential ligand upon interaction with P2Y1R might have therapeutic value for the treatment of prostate cancer.

Sero-Prevalence of SARS-CoV-2 Antibodies in High-Risk Populations in Vietnam.

As a response to the coronavirus disease 2019 (COVID-19) pandemic, Vietnam enforced strict quarantine, contact tracing and physical distancing policies resulting in one of the lowest numbers of individuals infected with severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) globally. This study aimed to determine the prevalence of SARS-CoV-2 antibody positivity among high-risk populations in Vietnam. A prevalence survey was undertaken within four communities in Vietnam, where at least two COVID-19 cases had been confirmed. Participants were classified according to the location of exposure: household contacts, close contacts, community members, and healthcare workers (HCWs) responsible for treating COVID-19 cases. Participants completed a baseline questionnaire and SARS-CoV-2 IgG antibodies were quantified using a commercial assay. A total of 3049 community members and 149 health care workers consented to the study. Among 13 individuals who were seropositive (0.4%), five household contacts (5/27, 18.5%), one close contact (1/53, 1.9%), and seven community members (7/2954, 0.2%) had detectable SARS-CoV-2 antibodies. All HCWs were negative for SARS-CoV-2 antibodies. Participants were tested a median of 15.1 (interquartile range from 14.9 to 15.2) weeks after exposure. Our study found a low prevalence of SARS-CoV-2 antibodies in high-risk communities and healthcare workers in communities in Vietnam with known COVID-19 cases.

Synedrella nodiflora (Linn.) Gaertn. inhibits inflammatory responses through the regulation of Syk in RAW 264.7 macrophages.

Synedrella nodiflora (Linn.) Gaertn. (S. nodiflora) has long been used for the treatment of inflammatory diseases, including liver disease, asthma, rheumatism and earache, in tropical countries throughout America, Asia and Africa. However, the biological effects of S. nodiflora have not been extensively studied at the molecular level. Notably, it remains unclear how S. nodiflora exerts anti-inflammatory activity. In the present study, the anti-inflammatory mechanism of a methanol extract of S. nodiflora (MSN) in RAW 264.7 macrophages activated by lipopolysaccharide (LPS) was investigated. Non-cytotoxic concentrations of MSN (≤400 µg/ml) decreased the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), which resulted in a decrease in nitric oxide and prostaglandin E2 (PGE2) production. The mRNA expression of pro-inflammatory cytokines such as interleukin (IL)-6, IL-1ß, and tumor necrosis factor (TNF)-α was reduced upon MSN treatment. In addition, the activation of spleen tyrosine kinase (Syk) and Akt was suppressed by MSN. Taken together, these findings recommend the traditional medicinal application of S. nodiflora in the treatment of several inflammation-associated diseases and indicate the possibility of MSN as a novel therapeutic reagent of inflammation-related diseases.

[Corrigendum] Methanol extract of Guettarda speciosa Linn. inhibits the production of inflammatory mediators through the inactivation of Syk and JNK in macrophages.

After the acceptance of the article and during the pre­publication stages, the author listed second on the paper, Young­Chang Cho, moved to a new affiliation (College of Pharmacy, Chonnam National University, Gwangju 61186, Korea). Therefore, the published paper should also have included details of the new affiliation as a 'Present address'. The author and affiliation information should have been shown as follows: HIEN THI THU LE1*, YOUNG­CHANG CHO1,2* and SAYEON CHO1. 1Laboratory of Molecular Pharmacological Cell Biology, College of Pharmacy, Chung­Ang University, Seoul 06974, Republic of Korea. *Contributed equally. 2Present address: College of Pharmacy, Chonnam National University, Gwangju 61186, Republic of Korea. The authors regret that this change was not made prior to the publication of their paper, and apologize for any inconvenience caused. [the original article was published in International Journal of Molecular Medicine 41: 1783­1791, 2018; DOI: 10.3892/ijmm.2018.3377].

Recent advances in microfluidic paper-based electrochemiluminescence analytical devices for point-of-care testing applications.

Electrogenerated chemiluminescence (ECL) is an effective method for detecting a wide range of analytes including metal ions, virulent DNA, pathogenic bacteria, tumor cells and glucose. The attractive features of paper including passive liquid transport and biocompatibility are the main two advantages of using paper as a biosensing platform. To achieve key factors in paper-based sensors, the fabrication procedures and the analysis methods are fine tuned to satisfy the requirements of the ultimate-users. Here, we review various ECL signal amplification labels, inexpensive and portable devices, such as rechargeable batteries, which have replaced traditional instrumentation and different light detection technologies used in paper ECL devices. We also highlight the current trends and developments in ECL paper-based microfluidic analytical devices, as well as recent applications of ECL-based detection methods and inexpensive microfluidic devices. We discuss various paper-based devices, including 3D-origami devices, and devices utilizing self-powered and bipolar electrodes. Significant efforts have also been dedicated towards paper based multiplexing analysis (multi-label, and the multi-analyte strategies) and integration of microfluidic lab-on-paper devices with competences for point-to-care diagnostics. This review finally tabulates systematized data on figures of merit and novel types of ECL labels, used for detection of various biomarkers and analytes.

Synthesis and preclinical validation of novel P2Y1 receptor ligands as a potent anti-prostate cancer agent.

Purinergic receptor is a potential drug target for neuropathic pain, Alzheimer disease, and prostate cancer. Focusing on the structure-based ligand discovery, docking analysis on the crystal structure of P2Y1 receptor (P2Y1R) with 923 derivatives of 1-indolinoalkyl 2-phenolic compound is performed to understand the molecular insights of the receptor. The structural model identified the top novel ligands, 426 (compound 1) and 636 (compound 2) having highest binding affinity with the docking score of -7.38 and -6.92. We have reported the interaction efficacy and the dynamics of P2Y1R protein with the ligands. The best hits synthesized were experimentally optimized as a potent P2Y1 agonists. These ligands exhibits anti-proliferative effect against the PC-3 and DU-145 cells (IC50 = 15 µM - 33 µM) with significant increase in the calcium level in dose- and time-dependent manner. Moreover, the activation of P2Y1R induced the apoptosis via Capase3/7 and ROS signaling pathway. Thus it is evidenced that the newly synthesized ligands, as a P2Y1R agonists could potentially act as a therapeutic drug for treating prostate cancer.

Methanol extract of Guettarda speciosa Linn. inhibits the production of inflammatory mediators through the inactivation of Syk and JNK in macrophages.

Guettarda speciosa Linn. (G. speciosa, Rubiaceae) has been used as a traditional medicinal plant in Asia for the treatment of various inflammatory conditions, including cough, fever and maternal postpartum infection. However, the mechanisms underlying the anti­inflammatory action of G. speciosa extracts have remained elusive. In the present study, the anti­inflammatory effects of the methanol extract of G. speciosa (MGS) were investigated in murine macrophages by measuring the production of inflammatory mediators and the underlying mechanisms of action by performing immunoblotting analysis of proteins that are potentially involved. MGS reduced nitric oxide (NO) production through regulation of the expression of inducible NO synthase (iNOS) in lipopolysaccharide­activated RAW 264.7 cells; however, cyclooxygenase­2, the enzyme responsible for prostaglandin E2 production, was not affected at the mRNA or protein level. MGS reduced interleukin­6 (IL­6) production, but had no effect on tumor necrosis factor (TNF)­α production. In addition, MGS suppressed the transcription of IL­6, but not that of IL­1ß and TNF­α. The effect of MGS on proinflammatory mediators resulted from the inhibition of the activation of spleen tyrosine kinase and c­Jun N­terminal kinase. In conclusion, the present study suggested that MGS may be a potential candidate for development as a therapeutic for alleviating inflammation.