Vol.46, No.2, 2022-Table of Contents

On the Cover


3D optical coherence tomography image of a basal cell carcinoma from human skin showing normal cells around the tumor in yellow (with a stiffness of about 1.0 MPa), tumor cells in red (with a stiffness of about 1.7 MPa), normal collagen in the dermis in blue (with a stiffness of about 2.3 MPa), and fibrotic collagen around the tumor in white (with a stiffness of about 10 MPa). The modulus data was collected using vibrational optical coherence tomography. The increased modulus of tumor cells and fibrous tissues deposited near the tumor underscore the relationship between cellular mutations and increases in modulus.
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  • Mechanotransduction-The relationship between gravity, cells and tensile loading in extracellular matrix
  • Abstract Gravity plays a central role in vertebrate development and evolution. Mechanotransduction involves the tensile tethering of veins and arteries, connections between the epidermis and dermis in skin, tensile stress concentrations that occur at tissue interfaces, cell-cell interactions, cell-collagen fiber stress transfer in extracellular matrix and fluid shear flow. While attention in the past has been directed at understanding the myriad of biochemical players associated with mechanotransduction pathways, less attention has been focused on determining the tensile mechanical behavior of tissues in vivo. Fibroblasts sit on the surface of collagen fibers in living skin and exert a retractile force on the… More
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  • New evidence for a role of Bisphenol A in cell integrity. Implications in the human population
  • Abstract Bisphenol A (BPA) is a xenoestrogen known for its implications for the endocrine systems and several other organs, including the kidneys. Recent renal studies have shown that BPA can induce alterations of the cytoskeleton and cell adhesion mechanisms such as a podocytopathy with proteinuria and hypertension, alterations involved in the progression of renal diseases. These data and the fact that BPA is known to be present in the urine of almost the entire population strongly suggest the critical need to reevaluate BPA exposures considered safe. More
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  • Alteration in the expression of microRNA-21 regulated target genes: Role in breast cancer
  • Abstract Breast cancer, also recognized as the principal cause of cancer-related deaths among women, is the second most familiar and prevalent form of cancer. New diagnostic and prognostic biomarkers that are highly specific are urgently needed for its early prognosis. MicroRNAs (miRNAs), a class of non-coding RNAs, are known to control the biological processes involving transcription, post-transcriptional and covalent modifications, splicing, translation, cell differentiation, proliferation, apoptosis, cancer progression, and invasion. Any dysregulation in miRNA expression, demonstrating their oncogenic and tumor-suppressive functions, contributes to cancer progression. MicroRNA-21 (miR-21), an ‘onco-miR’ in breast cancer, is involved in tumor progression and metastasis by suppressing… More
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  • A review from mesenchymal stem-cells and their small extracellular vesicles in tissue engineering
  • Abstract This review aims to offer a vision of the clinical reality of cell therapy today in intensive medicine. For this, it has been carried out a description of the properties, functions, and Mesenchymal Stem Cells (MSCS) sources to subsequently address the evidence in preclinical models and studies clinical trials with whole cells and models attributed to small extracellular vesicles (sEVs), nanoparticles made up of microvesicles secreted by cells with an effect on the extracellular matrix, and their impact as an alternative towards cell-free regenerative medicine. MSCs are cells that enhance the regenerative capacity which can be differentiated typically in different… More
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  • MicroRNA regulation and host interaction in response to Aspergillus exposure
  • Abstract Aspergillus is a group of conidial fungi, isolated from soil and litter, cause serious diseases in humans and animals. This ubiquitous fungus is prevalent in the air and inhalation of fungal spores is common. Fungal diseases from Aspergillus became a major health problem and are difficult to manage because they tend to be chronic and invasive, hard to diagnose and difficult to exterminate with antifungal drugs. Although, immune responses play vital roles in monitoring the fate of fungal infections and regulation of the immune responses against fungal infections might be an effective approach for controlling and reducing the pathological damages.… More
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  • The Potential Toxic Side Effects of Flavonoids
  • Abstract Flavonoids are a class of phytochemical molecules abundant in many plants, fruits, vegetables, and leaves. Flavonoids possess a series of significant biological activities, including anticancer, antioxidant, antiviral, and antiinflammatory properties. They become an important source of dietary supplements and natural health products. Though many studies confirmed the safety of flavonoids, the potential toxicity of flavonoids is still a remarkable field of research to be explored. The enthusiasm for flavonoids expressed by the public has sometimes overlooked their toxicity and also consumed the flavonoids exceeding the body requirements. The current review focused on the potential toxicity of flavonoids to make the… More
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  • Cervical cancer situation in Malaysia: A systematic literature review
  • Abstract Cervix cancer is one of Malaysia’s most significant cancers for women (around 12.9%, with an age-standardised incidence rate of 19.7 per 100,000). It was higher than other Asian, West, and even worldwide nations. The National Strategic Plan for Cancer Control Program 2016–2020 (Health Ministry) was presented to minimize cancer and mortality. The high incidence of cervical cancer in Malaysia is mainly due to women’s insufficient knowledge about its prevention and importance. Compared with traditional literature reviews, the systemic analysis provides many advantages. A clearer review process, a more prominent field of study, and essential priorities that can manage research bias… More
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  • Apigenin as a promising myocyte protectant against damage and degradation
  • Abstract Myocytes power the movement of all organs in the body. Damage to and degradation of myocytes causes hypokinesia and muscle-related degenerative diseases. Apigenin, a kind of flavone, is being used to treat many disorders. It exerts a host of different pharmacological activities, such as anti-inflammatory, anti-mutagenic, cardioprotective, and antioxidant effects. Accordingly, apigenin is considered a promising candidate for myocyte protection. In this review, we introduced the characteristics of apigenin. The means of apigenin protection of myocytes as well as the mechanism were summarized and discussed. The protective effects can be classified into proliferation-promoting, anti-inflammatory, atrophy-preventing, metabolism-increasing, and antioxidative effects. Additionally,… More
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  • Ubiquitin-like posttranslational modifications in NAFLD progression and treatment
  • Abstract Nonalcoholic fatty liver disease (NAFLD) is a long-lasting condition that affects the liver, destroying its function. Liver injury can cause steatosis and inflammation, and further activation of hepatic stellate cells (HSCs) often leads to the development of nonalcoholic liver fibrosis. The patient with NAFLD is at risk of developing advanced liver disease and complications, such as liver failure, hepatocellular carcinoma (HCC), and portal hypertension. Although our understanding of the cellular and molecular mechanisms of NAFLD has greatly improved in recent years, treatment remains limited. Analysis and characterization of protein posttranslational modifications (PTMs) could improve our understanding of NAFLD pathology and… More
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  • MicroRNA-181a is elevated by 10-hydroxycamptothecin and represses lung carcinoma progression by downregulating FOXP1
  • Abstract Tumor progression is usually characterized by proliferation, migration, and angiogenesis, which is essential for supplying both nutrients and oxygen to the tumor cells. Therefore, targeting angiogenesis has been considered a promising therapeutic strategy for cancer prevention and treatment. In the present study, we demonstrated that in addition to suppressing lung cancer cell proliferation and migration in vitro, 10-hydroxycamptothecin (10-HCPT) is also capable of inhibiting angiogenesis in vivo with a miR-181a-dependent manner. Mechanistically, by upregulating miR-181a, which in turn downregulating FOXP1, 10-HCPT can inhibit the PI3K/Akt/ERK signaling pathwaymediated angiogenesis. Furthermore, reduced levels of miR-181a have been found in both lung cancer… More
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  • Short term protective effect of digitoxin in sepsis-induced acute lung injury
  • Abstract Purpose: Digitoxin is a cardiac glycoside used in the treatment of heart failure. Inspired by its known anti-inflammatory effect, this study aims to investigate the effect of digoxin in a sepsis model and to bring to light its effect and underlying mechanism in acute lung injury (ALI). Method: 28 wistar albino rats were divided into 4 groups. Sepsis model is performed by the feces intraperitoneal-injection procedure (FIP). Results: TNF-a, CRP, IL-6, IL 1-Beta, lactic acid, and MDA values were significantly decreased in the FIP+digitoxin group compared to the FIP+Saline group. When the same groups were examined, histological improvements such as… More
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  • KRT4 suppresses oral squamous cell carcinoma development by reducing ATG4B-mediated autophagy
  • Abstract Head and neck squamous cell carcinoma is the sixth most common tumor worldwide, and half of head and neck squamous cell carcinoma patients are with oral squamous cell carcinoma (OSCC). 300,000 new cases of OSCC were reported annually. Even with multi-modality treatment, the prognosis of OSCC remains unsatisfactory. Thus, it is urgent to discover novel therapeutic targets for OSCC. Some microarray studies have revealed that Keratin 4 (KRT4) is downregulated in OSCC, whereas its role in OSCC development remains unknown. The present study revealed that KRT4 suppressed OSCC progression by inducing cell apoptosis and inhibiting cell invasion. In addition, KRT4… More
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  • Lysophosphatidylcholine acyltransferase 1 is involved in the regulation of exosome secretion and uptake in colorectal cancer cells
  • Abstract Lysophosphatidylcholine acyltransferase 1 (LPCAT1) is a phospholipid acyltransferase that promotes phospholipid synthesis and plasma membrane reconstruction. Exosomes play an important role in tumor metastasis. The release and uptake of exosomes are key steps of their functions and depend on plasma membrane fusion and plasma membrane receptors, respectively. The purpose of this study was to explore whether LPCAT1-induced plasma membrane remodeling would change the secretion and uptake behavior of exosomes in tumor cells. We first confirmed the abnormally high expression of LPCAT1 in colorectal cancer cells by quantitative real-time PCR (qPCR) and Western blot analysis. Then, SW620 cells were used as… More
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  • Elp3 modulates neural crest and colorectal cancer migration requiring functional integrity of HAT and SAM domains
  • Abstract Cell migration is a finely tuned biological process that often involves epithelial-mesenchymal transition (EMT). EMT is typically characterized by the upregulation of mesenchymal markers such as Snail1. This process has been shown to be of critical importance to normal developmental processes, including neural crest migration and invasion. Interestingly, similar mechanisms are utilized in disease processes, such as tumor metastasis and migration. Notably, EMT and EMT-like processes confer tumor cells with the ability to migrate, invade, and adopt stem cell-like properties that largely account for immunosuppression and tumor recurrence. Therefore, identifying sensitive EMT markers may contribute to cancer prognosis and diagnosis… More
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  • Neural stem cell-conditioned medium upregulated the PCMT1 expression and inhibited the phosphorylation of MST1 in SH-SY5Y cells induced by Aβ25-35
  • Abstract A progressive neurodegenerative disease, Alzheimer’s disease (AD). Studies suggest that highly expressed protein isoaspartate methyltransferase 1 (PCMT1) in brain tissue. In the current study, we explored the effects of neural stem cell-conditioned medium (NSC-CDM) on the PCMT1/MST1 pathway to alleviate Aβ25-35-induced damage in SH-SY5Y cells. Our data suggested that Aβ25-35 markedly inhibited cell viability. NSC-CDM or Neural stem cell-complete medium (NSC-CPM) had a suppression effect on toxicity when treatment with Aβ25-35, with a greater effect observed with NSC-CDM. Aβ25-35 + NSC-CDM group exhibited an increase in PCMT1 expression. sh-PCMT1 markedly decreased cell proliferation and suppressed the protective role of NSC-CDM… More
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  • Identification of tumorigenic risk genes in human placenta-derived mesenchymal stem cells treated with 3-methylcholanthrene
  • Abstract Mesenchymal stem cells (MSCs) capable of tumour topotaxis have been served as cellular vehicles to deliver anti-tumour agents. As cellular components of the tumour microenvironment, MSCs also affect tumour progression. However, the tumour transformation-related genes of MSCs remain unclear since either tumorigenic or tumour suppressor effects within these cells have been researched. Hence, we aimed to identify potential biomarkers indicative of tumorigenic risk by RNA-seq analysis of human placenta tissue-derived MSCs (hPTMSCs) exposed to the carcinogenic agent, 3-methylcholanthrene (3-MC). Twenty-nine tumour transformation-related genes and three pluripotency-related genes were appraised as differentially expressed genes (DEGs) in hPTMSCs. Overexpression of sfrp1 led… More
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  • M1 macrophage-derived exosomes moderate the differentiation of bone marrow mesenchymal stem cells
  • Abstract Differentiated macrophages have been proven to participate in the development of mesenchymal stem cells in different tissues. However, the regulatory processes remain obscure. Exosomes, which are key secretions of macrophages, have attracted increasing attention. Therefore, macrophage-derived exosomes may modulate the development of Bone marrow mesenchymal stem cells (BMMSCs). Different culture conditions were used to induce M1 polarization in THP1 cells. Subsequently, exosomes derived from unpolarized (M0) and polarized (M1) macrophages were isolated, BMMSCs were cultured with normal complete medium or inductive medium supplemented with M0 or M1 derived exosomes, and the osteogenic capacity of the BMMSCs was measured and analyzed.… More
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  • DTL facilitates the Fanconi anemia pathway for ultraviolet-induced DNA repair in retinal pigment epithelial cells
  • Abstract The excessive energy of light, especially the invisible rays with lower wavelength, is basically absorbed by retinal pigment epithelium (RPE) and usually causes DNA damage. The molecular mechanism behind DNA damage repair response to this frequent stress in RPE is not clearly understood. In this study, we determined that the Fanconi anemia (FA) pathway was activated in human RPE ARPE-19 cells after ultraviolet (UV) B and C treatment. Moreover, immunoprecipitation (IP) of FANCD2 indicated that denticleless E3 ubiquitin protein ligase homolog (DTL) closely interacted with FANCD2. Knockdown of DTL weakened the activity of the FA pathway in ARPE-19 cells responding… More
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  • Revisiting miR-155 in intervertebral disc degeneration: blood cell signature and local cell-free profiles
  • Abstract We unraveled the expression profiles of coding-noncoding RNAs in intervertebral disc degeneration (IDD). However, it remains elusive regarding miR-155 expression in peripheral blood mononuclear cells (PBMCs) and local extracellular space in IDD. The study aimed for investigating the miR-155 expression of PBMCs, extracellular miRNAs (ex-miRNAs) of human nucleus pulposus (NP) tissues, and morphological changes of cell death in the IDD process. Here, we harvested peripheral blood and NP samples from scoliosis and IDD patients as control and degenerative groups, respectively. Then standard Ficoll density-gradient centrifugation was used to isolate PBMCs. The two subpopulations of PBMCs were divided based on the… More
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  • Potential genomic biomarkers of obesity and its comorbidities for phthalates and bisphenol A mixture: In silico toxicogenomic approach
  • Abstract This in silico toxicogenomic study aims to explore the relationship between phthalates and bisphenol A (BPA) co-exposure and obesity, as well as its comorbid conditions, in order to construct a possible set of genomic biomarkers. The Comparative Toxicogenomics Database (CTD; http://ctd.mdibl.org) was used as the main data mining tool, along with GeneMania (https://genemania.org), ToppGene Suite (https://toppgene.cchmc.org) and DisGeNET (http://www.disgenet.org). Among the phthalates, bis(2-ethylhexyl) phthalate (DEHP) and dibutyl phthalate (DBP) were chosen as the most frequently curated phthalates in CTD, which also share similar mechanisms of toxicity. DEHP, DBP and BPA interacted with 84, 90 and 194 obesity-related genes/proteins, involved in… More
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  • Characterization of endogenous nucleic acids that bind to NgAgo in Natronobacterium gregoryi sp2 cells
  • Abstract As nucleic acid-guided endonucleases, some prokaryotic Argonautes have been used as programmable nucleases. Natronobacterium gregoryi Argonaute (NgAgo) has also been proposed for gene editing, but this remains very controversial. Until now, the endogenous nucleic acids that bind to NgAgo in Natronobacterium gregoryi sp2 (N. gregoryi sp2) have not been characterized. We expressed the conserved PIWI domain of NgAgo and used it to induce anti-PIWI antibody. We also cultured the N. gregoryi sp2 strain and performed immunoprecipitation, chromatin immunoprecipitation (ChIP), and RNA immunoprecipitation (RIP) assays. The nucleic acids that endogenously bound NgAgo in N. gregoryi sp2 cells were sequenced and analyzed.… More
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  • Application of VIGS system to explore the function of common wheat TaADF7
  • Abstract As an allohexaploid plant, common wheat has a complex gene structure, making it difficult to study its gene function. Virus-induced gene silencing (VIGS) is an important tool for the rapid analysis of plant gene function. In this study, the gene silencing system, namely, barley stripe mosaic virus (BSMV)-VIGS induced by BSMV was used to silence the wheat phytoene desaturase (TaPDS) and actin depolymerization factor (TaADF7) genes and determine the effect of gene silencing on wheat. TaPDS was used as an indicator gene to determine the feasibility of VIGS system, while TaADF7 was used as a test gene to determine its… More
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