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Fulltext Anti-proliferation of MDA-MB-231 Cells by Averrhoa bilimbi Extract is Associated with G0/G1 Perturbation and Mitochondria-mediated Apoptosis Independent of p53

Yan, S. W.., Asmah, R.

International Food Research Journal, 2017;24(3):1331-1337.
MyJurnal

Practiced as folk medicine since ancient times, bilimbi (Averrhoa bilimbi) is commonly
consumed and widely cultivated in Malaysia. In search for naturally occurring anticancer
agents, a potential fruit extract was found to exert anticancer properties in vitro without any
cytotoxic effect on normal cells. This study investigated the anti-proliferative effect and
underlying cell death pathway induced by bilimbi ethanolic extract on human non-hormonedependent
breast cancer cell line, MDA-MB-231. Anticancer potential of bilimbi extract was
conducted by investigating the in vitro growth inhibitory effect, DNA fragmentation, cell cycle
progression and anti-proliferation assay. Release of caspases, cytochrome c and apoptotic
proteins were demonstrated to determine the mechanism of cell death pathway. Findings
revealed that bilimbi inhibited growth of MDA-MB-231 cells through the induction of
apoptosis mediated by cell cycle arrest at G0/G1 checkpoint. Released of cytochrome c coupled
with up-regulation of caspase-3/7, caspase-9 and Bax pro-apoptotic proteins in addition to
down-regulation of dysfunctional p53 and Bcl-2 anti-apoptotic proteins implied that bilimbi
induced a p53-independent mitochondrial apoptosis pathway in MDA-MB-231. These results
suggest that bilimbi could induce tumor cell anti-proliferation through apoptosis. As a natural
product, bilimbi could be a promising anticancer agent and an inexpensive approach to cancer
chemoprevention strategy.
Fulltext Exploring the Factors That Influence Stakeholder Participation in Decision-Making for the Moat System Restoration Project in Tianchang City, China

Yan S, Ibrahim RB

ScientificWorldJournal, 2023;2023:9969589.
PMID: 38021481 DOI: 10.1155/2023/9969589

The driving factors have a critical effect on shaping stakeholder behavior toward participating in decision-making for river restoration initiatives. The participation of stakeholders is a vital determinant for increasing public confidence in the government and enhancing the acceptance of government decisions. Conversely, insufficient stakeholder participation in decision-making may lead to resistance to decisions on river restoration projects. Thus, the primary purpose of this investigation is to shed light on the complex interactions between the various drivers that underpin stakeholder participation in the context of the Moat System Restoration Project (MSRP). The extended Theory of Planned Behavior (TPB) describes the relationships between seven drivers that have positively influenced stakeholder participation behaviors: stakeholder attitude, priority, risk perception, trust in government decisions, motivation, intention, and knowledge. The empirical underpinning of this research was obtained through a questionnaire survey conducted in Tianchang, China, encompassing a sample size of 473. The empirical findings discern that stakeholder attitudes vis-à-vis the MSRP favorably influence stakeholder participation behaviors. Additionally, stakeholder motivation and intention have been discerned as catalysts for heightened stakeholder participation behavior. These findings promise to furnish invaluable insights, benefit forthcoming river restoration initiatives, and equip decision-makers with a profound understanding of strategies to enhance stakeholder participation.
Phylogeography of Tetrancistrum nebulosi (Monogenea, Dactylogyridae) on the host of mottled spinefoot (Siganus fuscescens) in the South China Sea, inferred from mitochondrial COI and ND2 genes

Wang M, Yan S, Brown CL, Shaharom-Harrison F, Shi SF, Yang TB

Mitochondrial DNA A DNA Mapp Seq Anal, 2016 11;27(6):3865-3875.
PMID: 25319302

To examine the phylogeographical pattern of Tetrancistrum nebulosi (Monogenea, Dactylogyridae) in the South China Sea, fragments of mitochondrial cytochrome c oxidase subunit I and NADH dehydrogenase subunit 2 genes were obtained for 220 individuals collected from 8 localities along the southeast coast of China and 1 locality in Terengganu, Malaysia. Based on these two genes, two and three distinct clades with geographic signals were revealed on the phylogenetic trees respectively. The divergence between these clades was estimated to occur in the late Pleistocene. Analysis of molecular variance and pairwise FSTsuggested a high rate of gene flow among individuals sampled from the Chinese coast, but with obvious genetic differentiation from the Malaysian population. Mismatch distribution and neutrality tests indicated that the T. nebulosi population experienced expansion in Pleistocene low sea level periods. Vicariance was considered to account for the genetic divergence between Chinese and Malaysian populations, while sea level fluctuations and mainland-island connections during glacial cycles were associated with the slight genetic divergence between the populations along the mainland coast of China and those off Sanya. On the contrary, oceanographic circulations and host migration could lead to genetic homogeneity of populations distributed along the mainland coast of China.
Effect of maternal age, birth weight and infant sex on total nucleated cell (TNC) count and volume of umbilical cord blood (UCB) collected

Choong SN, Ng YK, Kamalan A, Saraswathy S, Goh EH, Lee MJ, et al.

Med J Malaysia, 2008 Jul;63 Suppl A:55-6.
PMID: 19024981

This study evaluates the effect of maternal age, birth weight and infant sex on two main UCB parameters for use and long-term cryopreservation: TNC and volume. Data from 1000 UCB units were collected and analyzed in this study. The results indicate that TNC is correlated to infant birth weight and sex but not maternal age at delivery. Volume is only correlated to birth weight but not maternal age and infant sex.
Fulltext Deep Neural Network-Based Fusion Localization Using Smartphones

Yan S, Su Y, Xiao J, Luo X, Ji Y, Ghazali KHB

Sensors (Basel), 2023 Oct 24;23(21).
PMID: 37960380 DOI: 10.3390/s23218680

Indoor location-based services (LBS) have tremendous practical and social value in intelligent life due to the pervasiveness of smartphones. The magnetic field-based localization method has been an interesting research hotspot because of its temporal stability, ubiquitousness, infrastructure-free nature, and good compatibility with smartphones. However, utilizing discrete magnetic signals may result in ambiguous localization features caused by random noise and similar magnetic signals in complex symmetric and large-scale indoor environments. To address this issue, we propose a deep neural network-based fusion indoor localization system that integrates magnetic and pedestrian dead reckoning (PDR). In this system, we first propose a ResNet-GRU-LSTM neural network model to achieve magnetic localization more accurately. Afterward, we put forward a multifeatured-driven step length estimation. A hierarchy GRU (H-GRU) neural network model is proposed, and a multidimensional dataset using acceleration and a gyroscope is constructed to extract more valid characteristics. Finally, more reliable and accurate pedestrian localization can be achieved under the particle filter framework. Experiments were conducted at two trial sites with two pedestrians and four smartphones. Results demonstrate that the proposed system achieves better accuracy and robustness than other traditional localization algorithms. Moreover, the proposed system exhibits good generality and practicality in real-time localization with low cost and low computational complexity.
Fulltext Emergence and adaptive evolution of Nipah virus

Li K, Yan S, Wang N, He W, Guan H, He C, et al.

Transbound Emerg Dis, 2020 Jan;67(1):121-132.
PMID: 31408582 DOI: 10.1111/tbed.13330

Since its first emergence in 1998 in Malaysia, Nipah virus (NiV) has become a great threat to domestic animals and humans. Sporadic outbreaks associated with human-to-human transmission caused hundreds of human fatalities. Here, we collected all available NiV sequences and combined phylogenetics, molecular selection, structural biology and receptor analysis to study the emergence and adaptive evolution of NiV. NiV can be divided into two main lineages including the Bangladesh and Malaysia lineages. We formly confirmed a significant association with geography which is probably the result of long-term evolution of NiV in local bat population. The two NiV lineages differ in many amino acids; one change in the fusion protein might be involved in its activation via binding to the G protein. We also identified adaptive and positively selected sites in many viral proteins. In the receptor-binding G protein, we found that sites 384, 386 and especially 498 of G protein might modulate receptor-binding affinity and thus contribute to the host jump from bats to humans via the adaption to bind the human ephrin-B2 receptor. We also found that site 1645 in the connector domain of L was positive selected and involved in adaptive evolution; this site might add methyl groups to the cap structure present at the 5'-end of the RNA and thus modulate its activity. This study provides insight to assist the design of early detection methods for NiV to assess its epidemic potential in humans.
Soil carbon supplementation: Improvement of root-surrounding soil bacterial communities, sugar and starch content in tobacco (N. tabacum)

Yan S, Ren T, Wan Mahari WA, Feng H, Xu C, Yun F, et al.

Sci Total Environ, 2021 Aug 24;802:149835.
PMID: 34461468 DOI: 10.1016/j.scitotenv.2021.149835

Soil carbon supplementation is known to stimulate plant growth by improving soil fertility and plant nutrient uptake. However, the underlying process and chemical mechanism that could explain the interrelationship between soil carbon supplementation, soil micro-ecology, and the growth and quality of plant remain unclear. In this study, we investigated the influence and mechanism of soil carbon supplementation on the bacterial community, chemical cycling, mineral nutrition absorption, growth and properties of tobacco leaves. The soil carbon supplementation increased amino acid, carbohydrates, chemical energy metabolism, and bacterial richness in the soil. This led to increased content of sugar (23.75%), starch (13.25%), and chlorophyll (10.56%) in tobacco leaves. Linear discriminant analysis revealed 49 key phylotypes and significant increment of some of the Plant Growth-Promoting Rhizobacteria (PGPR) genera (Bacillus, Novosphingobium, Pseudomonas, Sphingomonas) in the rhizosphere, which can influence the tobacco growth. Partial Least Squares Path Modeling (PLS-PM) showed that soil carbon supplementation positively affected the sugar and starch contents in tobacco leaves by possibly altering the photosynthesis pathway towards increasing the aroma of the leaves, thus contributing to enhanced tobacco flavor. These findings are useful for understanding the influence of soil carbon supplementation on bacterial community for improving the yields and quality of tobacco in industrial plantation.
Fulltext Lixisenatide treatment improves glycaemic control in Asian patients with type 2 diabetes mellitus inadequately controlled on metformin with or without sulfonylurea: a randomized, double-blind, placebo-controlled, 24-week trial (GetGoal-M-Asia)

Yu Pan C, Han P, Liu X, Yan S, Feng P, Zhou Z, et al.

Diabetes Metab Res Rev, 2014 Nov;30(8):726-35.
PMID: 24639432 DOI: 10.1002/dmrr.2541

BACKGROUND: This study assessed the efficacy and safety of the once-daily glucagon-like peptide-1 receptor agonist, lixisenatide, in Asian patients with type 2 diabetes mellitus inadequately controlled on metformin ± sulfonylurea.
METHODS: In this 24-week, double-blind, placebo-controlled, multinational study, patients were randomized to lixisenatide 20 µg once daily or placebo. The primary endpoint was absolute change in glycated haemoglobin (HbA1c ) from baseline to week 24.
RESULTS: A total of 391 patients were randomized. Lixisenatide significantly reduced HbA1c levels compared with placebo (LS mean difference: -0.36%, p = 0.0004). A significantly higher proportion of lixisenatide-treated patients achieved HbA1c targets of <7% (p = 0.003) and ≤6.5% (p = 0.001) versus placebo. Lixisenatide was associated with a statistically significant reduction in 2-h postprandial plasma glucose after a standardized breakfast versus placebo (LS mean difference: -4.28 mmol/L, p
The effect of acupuncture on lateral habenular nucleus and intestinal microflora in depression model rats

Chen W, Chen Y, Aslam MS, Shen J, Tong T, Yan S, et al.

Behav Brain Res, 2023 Oct 18;455:114627.
PMID: 37619770 DOI: 10.1016/j.bbr.2023.114627

BACKGROUND: Depression is a severe emotional condition that significantly affects the quality of life. Acupuncture exerts preventive effects on depression in rats with post-chronic unpredictable mild stress (CUMS). Methods The study involved chronic unpredictable mild stress (CUMS) depression model mice to administer acupuncture as a preventative measure to investigate the mechanism of acupuncture's antidepressant and observe the effect of acupuncture on impact via the Lateral Habenula (LHb) and Gut-Liver-Brain Axis. The researcher investigated molecules correlating with a nitric oxide/cyclic guanosine monophosphate (NO/cGMP) pathway and assessed inflammation in the LHb and liver. In addition, 16 S rDNA bioinformatics study revealed the quantity and variety of gut microbiota. Rats were randomly divided into five groups: control (CON), CUMS, CUMS + acupuncture (AP), CUMS + fluoxetine (FX) and CUMS + N(G) -nitro -L- arginine methyl ester (LNAME) group. Except for the CON group, other rats were exposed to CUMS condition for 28 days. Simultaneously, manual acupuncture (at Fengfu and Shangxing acupoints, once every other day) and fluoxetine gavage (2.1 mg/kg, 0.21 mg/mL, daily) were conducted to the groups of AP and FX, respectively, after stressors. Rats in LNAME group were treated with LNAME normal saline (10 mg/kg, 1 mg/mL, i.p.) solution. Behavioural tests and biological detection methods were conducted sequentially to evaluate depressionlike phenotype in rats.
RESULTS: The results showed CUMS induced depression-like behaviours, hyper-activation of NO/cGMP signaling pathway, inflammation in serum, LHb and liver, and dysbiosis of the gut microbiota. These changes could be prevented and ameliorated by acupuncture to varying extents.
CONCLUSION: Acupuncture prevented and attenuated depression-like phenotype induced by CUMS, possibly via regulating the NO/cGMP signaling pathway and thus improving inflammation in serum, LHb and liver, and gut microbiota dysbiosis. In addition, these can be evidence of the existence of the gut-liver-brain axis.
Fulltext Electroacupuncture ameliorates chronic unpredictable mild stress-induced depression-like behavior and cognitive impairment through suppressing oxidative stress and neuroinflammation in rats

Tong T, Hao C, Shen J, Liu S, Yan S, Aslam MS, et al.

Brain Res Bull, 2024 Jan;206:110838.
PMID: 38123022 DOI: 10.1016/j.brainresbull.2023.110838

BACKGROUND: Depression is associated with lowered mood, anxiety, anhedonia, cognitive impairments, and even suicidal tendencies in severe cases. Yet few studies have directed acupuncture's mechanism toward enhancing axonal repair correlated with synaptic plasticity and anti-inflammatory effects related to oxidative stress in the hippocampus.
METHODS: Male Sprague-Dawley (SD) rats were randomly divided into control group (CON), chronic unpredictable mild stress (CUMS) group, CUMS + electroacupuncture group (EA), and CUMS + fluoxetine group (FLX) (n = 10/group). Rats were given a 28-day treatment at the Shangxing (GV23) and Fengfu (GV16) acupoints with electroacupuncture or fluoxetine (2.1 mg/kg).
RESULTS: Rats exposed to CUMS induced depression-like behaviors and spatial learning-memory impairment, changed the ionized calcium binding adaptor molecule 1 (IBA-1), Vglut1, myelin basic protein (MBP), and postsynaptic density protein 95 (PSD95) level of hippocampal, increased the Nod-like receptor protein 3 (NLRP3), atypical squamous cell (ASC), Caspase level and hippocampal reactive oxygen species (ROS), and prompted the activation of Epha4-mediated signaling and an inflammatory response. Conversely, electroacupuncture administration reduced these changes and prevented depression-like behaviors and cognitive impairment. Electroacupuncture also promoted hippocampal expression of Sirtuin1(SIRT1), Nuclear factor erythroid 2-like (Nrf2), Heme oxygenase-1 (HO-1); reduced the expression of interleukin-1β (IL-1β), interleukin-18 (IL-18), and tumor necrosis factor-alpha (TNF-α); and prevented neural damage, particularly the synaptic myelin sheath, and neuroinflammation by regulating Eph receptor A4 (EphA4) in the hippocampal.
CONCLUSION: These results indicate that electroacupuncture prevents depression-like behaviors with cognitive impairment and synaptic and neuronal damage, probably by reducing EphA4, which mediates ROS hyperfunction and the inflammatory response.
Fulltext Acupuncture alleviates CUMS-induced depression-like behaviors of rats by regulating oxidative stress, neuroinflammation and ferroptosis

Shen J, Hao C, Yuan S, Chen W, Tong T, Chen Y, et al.

Brain Res, 2024 Mar 01;1826:148715.
PMID: 38142722 DOI: 10.1016/j.brainres.2023.148715

BACKGROUND: The treatment of depression with acupuncture has been documented. The mechanism behind acupuncture's curative and preventative effects is still unknown.
METHODS: The current study examined the effects of acupuncture on depression-like behaviors in a rat model of chronic unpredictable mild stress (CUMS), while also exploring its potential mechanisms. A total of six groups of rats were randomly assigned: control, CUMS, acupuncture, fluoxetine, acupoint catgut embedding and sham acupoint catgut embedding. Fluoxetine (2.1 mg/kg) and acupoint catgut embedding were used for comparative research to acupuncture. The modelling evaluation is measured by body weight and behavior tests. Western blotting and reverse transcription-polymerase chain reaction were used to detect the proteins and mRNA expression of Silent information regulator 1 (Sirt1)/ nuclear factor-erythroid 2-related factor 2 (Nrf2)/ heme oxygenase-1 (HO-1)/ Glutathione peroxidase 4 (GPX4) pathway in the hippocampus. The expression of oxidative stress (OS)-related proteins and inflammatory cytokines in the serum was detected with ELISA. Immunofluorescence showed microglia and astrocytes activity in the hippocampus.
RESULTS: Acupuncture and fluoxetine could alleviate CUMS-induced depression-like behaviors. Acupuncture was also found to effectively reverse the levels of MDA, SOD, GSH, GSH-PX and T-AOC, IL-1β, IL-6 and TNF-α in the serum of CUMS-induced rats. Rats with CUMS showed decreased levels of Sirt1, Nrf2, HO-1 and GPX4 in the hippocampus, while acupuncture treatment could partly reverse the diminished effects. In addition, acupuncture treatment significantly reduced the activation of hippocampal microglia and astrocytes in CUMS-induced rats.
CONCLUSION: The study's findings indicate that acupuncture has the potential to mitigate depression-like behaviors in rats induced with CUMS by mitigating OS and reducing neuroinflammation.
Fulltext Regulation of hepatic insulin signaling and glucose homeostasis by sphingosine kinase 2

Aji G, Huang Y, Ng ML, Wang W, Lan T, Li M, et al.

Proc Natl Acad Sci U S A, 2020 09 29;117(39):24434-24442.
PMID: 32917816 DOI: 10.1073/pnas.2007856117

Sphingolipid dysregulation is often associated with insulin resistance, while the enzymes controlling sphingolipid metabolism are emerging as therapeutic targets for improving insulin sensitivity. We report herein that sphingosine kinase 2 (SphK2), a key enzyme in sphingolipid catabolism, plays a critical role in the regulation of hepatic insulin signaling and glucose homeostasis both in vitro and in vivo. Hepatocyte-specific Sphk2 knockout mice exhibit pronounced insulin resistance and glucose intolerance. Likewise, SphK2-deficient hepatocytes are resistant to insulin-induced activation of the phosphoinositide 3-kinase (PI3K)-Akt-FoxO1 pathway and elevated hepatic glucose production. Mechanistically, SphK2 deficiency leads to the accumulation of sphingosine that, in turn, suppresses hepatic insulin signaling by inhibiting PI3K activation in hepatocytes. Either reexpressing functional SphK2 or pharmacologically inhibiting sphingosine production restores insulin sensitivity in SphK2-deficient hepatocytes. In conclusion, the current study provides both experimental findings and mechanistic data showing that SphK2 and sphingosine in the liver are critical regulators of insulin sensitivity and glucose homeostasis.
Fulltext Rapid Targeted Next-Generation Sequencing Platform for Molecular Screening and Clinical Genotyping in Subjects with Hemoglobinopathies

Shang X, Peng Z, Ye Y, Asan, Zhang X, Chen Y, et al.

EBioMedicine, 2017 Sep;23:150-159.
PMID: 28865746 DOI: 10.1016/j.ebiom.2017.08.015

Hemoglobinopathies are among the most common autosomal-recessive disorders worldwide. A comprehensive next-generation sequencing (NGS) test would greatly facilitate screening and diagnosis of these disorders. An NGS panel targeting the coding regions of hemoglobin genes and four modifier genes was designed. We validated the assay by using 2522 subjects affected with hemoglobinopathies and applied it to carrier testing in a cohort of 10,111 couples who were also screened through traditional methods. In the clinical genotyping analysis of 1182 β-thalassemia subjects, we identified a group of additional variants that can be used for accurate diagnosis. In the molecular screening analysis of the 10,111 couples, we detected 4180 individuals in total who carried 4840 mutant alleles, and identified 186 couples at risk of having affected offspring. 12.1% of the pathogenic or likely pathogenic variants identified by our NGS assay, which were undetectable by traditional methods. Compared with the traditional methods, our assay identified an additional at-risk 35 couples. We describe a comprehensive NGS-based test that offers advantages over the traditional screening/molecular testing methods. To our knowledge, this is among the first large-scale population study to systematically evaluate the application of an NGS technique in carrier screening and molecular diagnosis of hemoglobinopathies.
Evidence for the Higgs Boson Decay to a Z Boson and a Photon at the LHC

Aad G, Abbott B, Abeling K, Abicht NJ, Abidi SH, Aboulhorma A, et al.

Phys Rev Lett, 2024 Jan 12;132(2):021803.
PMID: 38277607 DOI: 10.1103/PhysRevLett.132.021803

The first evidence for the Higgs boson decay to a Z boson and a photon is presented, with a statistical significance of 3.4 standard deviations. The result is derived from a combined analysis of the searches performed by the ATLAS and CMS Collaborations with proton-proton collision datasets collected at the CERN Large Hadron Collider (LHC) from 2015 to 2018. These correspond to integrated luminosities of around 140 fb^{-1} for each experiment, at a center-of-mass energy of 13 TeV. The measured signal yield is 2.2±0.7 times the standard model prediction, and agrees with the theoretical expectation within 1.9 standard deviations.
Fulltext Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1

Klionsky DJ, Abdel-Aziz AK, Abdelfatah S, Abdellatif M, Abdoli A, Abel S, et al.

Autophagy, 2021 Jan;17(1):1-382.
PMID: 33634751 DOI: 10.1080/15548627.2020.1797280

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field.

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