Authors and Reviewers
Articles in press have been peer-reviewed and accepted, which are not yet assigned to volumes /issues, but are citable by Digital Object Identifier (DOI).
Current cell-based biosensors have progressed substantially from mere alternatives to molecular bioreceptors into enabling tools for interfacing molecular machineries and gene circuits with microelectronics and for developing groundbreaking sensing and theragnostic platforms. The recent literature concerning whole-cell biosensors is reviewed with an emphasis on mammalian cells, and the challenges and breakthroughs brought along in biomedical analyses through novel biosensing concepts and the synthetic biology toolbox. These recent innovations allow development of cell-based biosensing platforms having tailored performances and capable to reach the levels of sensitivity, dynamic range, and stability suitable for high analytic/medical relevance. They also pave the way for the construction of flexible biosensing platforms with utility across biological research and clinical applications. The work is intended to stimulate interest in generation of cell-based biosensors and improve their acceptance and exploitation.
Magnetic particle-based immunoassays are widely used in microbiology-related assays for both microbial capture, separation, analysis, and detection. Besides facilitating sample operation, the implementation of micro-to-nanometer scale magnetic beads as a solid support potentially shortens the incubation time (for magnetic immuno capture) from several hours to less than an hour. Analytical technologies based on magnetic beads offer a rapid, effective and inexpensive way to separate and concentrate the target analytes prior to detection. Magneto-immuno separation uses magnetic particles coated with specific antibodies to capture target microorganisms, bear the corresponding antigens, and subsequently separate them from the sample matrix in a magnetic field. The method has been proven effective in separating various types of pathogenic bacteria from environmental water samples and in eliminating background interferences. Magnetic particles are often used to capture target cells (pathogenic bacteria) from samples. In most commercially available assays, the actual identification and quantitation of the captured cells is then performed by classical microbiological assays. This review highlights the most sensitive analytic methods (i.e., long-range surface plasmon resonance and electrochemical impedance spectroscopy) to detect magnetically tagged bacteria in conjunction with magnetic actuation.
Mechanotransduction, a conversion of mechanical forces into biochemical signals, is essential for human development and physiology. It is observable at all levels ranging from the whole body, organs, tissues, organelles down to molecules. Dysregulation results in various diseases such as muscular dystrophies, hypertension-induced vascular and cardiac hypertrophy, altered bone repair and cell deaths. Since mechanotransduction occurs at nanoscale, nanosciences and applied nanotechnology are powerful for studying molecular mechanisms and pathways of mechanotransduction. Atomic force microscopy, magnetic and optical tweezers are commonly used for force measurement and manipulation at the single molecular level. Force is also used to control cells, topographically and mechanically by specific types of nano materials for tissue engineering. Mechanotransduction research will become increasingly important as a sub-discipline under nanomedicine. Here we review nanotechnology approaches using force measurements and manipulations at the molecular and cellular levels during mechanotransduction, which has been increasingly play important role in the advancement of nanomedicine.
Accurate targeting of vesicular acetylcholine transporter (VAChT) to synaptic vesicles (SVs) is indispensable for efficient cholinergic transmission. Previous studies have suggested that the dileucine motif within the C-terminus of the transporter is sufficient for its targeting to SVs. However, the cytosolic mechanism underlying specific regulation of VAChT trafficking and targeting to SVs is still unclear. Here we use the C-terminus of VAChT as bait in a yeast-two-hybrid screen to identify sorting nexin 5 (SNX5) as its novel interacting protein. SNX5 is detected in the SVs enriched LP2 subcellular fraction of rat brain homogenate and shows strong colocalization with VAChT in both brain sections and PC12 cells. Binding assays suggest that the C-terminal domain of VAChT can interact with both BAR and PX domain of SNX5. Depletion of SNX5 enhances the degradation of VAChT and the process is mediated through the lysosomal pathway. More importantly, we find that, in PC12 cells, the depletion of SNX5 expression significantly decreases the synaptic vesicle-like vesicles (SVLVs) localization of VAChT. Therefore, the results suggest that SNX5 is a novel regulator for both stability and SV targeting of VAChT.
The Journal of Biomedical Research--2021, 35(3)
Contrast-enhanced computed tomography (CT) contributes to the increasing detection of pancreatic neuroendocrine neoplasms (PNENs). Nevertheless, its value for differentiating pathological tumor grades is not well recognized. In this report, we have conducted a retrospective study on the relationship between the 2017 World Health Organization (WHO) classification and CT imaging features in 94 patients. Most of the investigated features eventually provided statistically significant indicators for discerning PNENs G3 from PNENs G1/G2, including tumor size, shape, margin, heterogeneity, intratumoral blood vessels, vascular invasion, enhancement pattern in both contrast phases, enhancement degree in both phases, tumor-to-pancreas contrast ratio in both phases, common bile duct dilatation, lymph node metastases, and liver metastases. Ill-defined tumor margin was an independent predictor for PNENs G3 with the highest area under the curve (AUC) of 0.906 in the multivariable logistic regression and receiver operating characteristic curve analysis. The portal enhancement ratio (PER) was shown the highest AUC of 0.855 in terms of quantitative features. Our data suggest that the traditional contrast-enhanced CT still plays a vital role in differentiation of tumor grades and heterogeneity analysis prior to treatment.
J Biomed Res 2021, 35(3): 189-196.
doi: 10.7555/JBR.34.20200082
Triple-negative breast cancer (TNBC) has a poor prognosis and typically earlier onset of metastasis in comparison with other breast cancer subtypes. It has been reported that insulin receptor (INSR) is downregulated in TNBC, however, its clinical significance and functions in TNBC remain to be elucidated. In this study, we found that INSR expression was significantly downregulated in TNBC, and overexpression of INSR suppressed cell migration and invasion in TNBC. In addition, the survival rate of breast cancer patients with low INSR expression was lower than that of patients with high INSR expression. INSR expression was significantly correlated with lymph node metastasis, clinical tumor stages, ER status, PR status, and the proliferation index Ki-67 expression. In summary, our study suggests that INSR may serve as a biomarker for breast cancer prognosis and it may be a potential target for TNBC treatment.
J Biomed Res 2021, 35(3): 197-205.
doi: 10.7555/JBR.34.20200153
Obesity is an escalating global pandemic posing a serious threat to human health. The intervention therapy using weight-reducing drugs, accompanied by lifestyle modification, is a strategy for the treatment of obesity. In the present study, we explored the role of fucoidan, a seaweed compound, on high-fat diet (HFD)-induced obesity in mice. We found that fucoidan treatment significantly reduced the body fat and caused redistribution of visceral and subcutaneous fat in HFD-fed mice. Meanwhile, fucoidan treatment inhibited adipocyte hypertrophy and inflammation in adipose tissue. Collectively, these results suggest that fucoidan may be a promising treatment for obesity and obesity-induced complications.
Periodontitis is a highly prevalent, chronic, non-specific, and immunologically devastating disease of periodontal tissues, caused by microbial infection. This study aims to examine the efficacy and protective mechanism of triclosan (TCS), a bisphenolic, non-cationic component of oral care products, against periodontal inflammation induced by lipopolysaccharide purified from Porphyromonas gingivalis (LPS-PG). TCS markedly downregulated interleukin-6 (IL-6), IL-8, and IL-15 in human periodontal ligament fibroblasts (HPDLFs) treated with LPS-PG. By using a liquid chromatography-tandem mass spectrometry (LC-MS/MS) approach, 318 differentially expressed proteins (161 upregulated and 157 downregulated) were identified in TCS-pretreated HPDLFs. TCS upregulated HSPA5 and HSP90B1 but downregulated HSPA2. Besides, TCS upregulated miR-548i in HPDLFs, which downregulated IL-15. These results indicate that TCS attenuates the activation of HPDLFs and downregulates the inflammatory cytokines through various mechanisms, thus highlighting its protective role in periodontal inflammation.
SARS-CoV-2 encoded microRNAs are involved in the process of virus infection and host immune response
J Biomed Res 2021, 35(3): 216-227.
doi: 10.7555/JBR.35.20200154
The outbreak of COVID-19 caused by SARS-CoV-2 is spreading worldwide, with the pathogenesis mostly unclear. Both virus and host-derived microRNA (miRNA) play essential roles in the pathology of virus infection. This study aims to uncover the mechanism for SARS-CoV-2 pathogenicity from the perspective of miRNA. We scanned the SARS-CoV-2 genome for putative miRNA genes and miRNA targets and conducted in vivo experiments to validate the virus-encoded miRNAs and their regulatory role on the putative targets. One of such virus-encoded miRNAs, MR147-3p, was overexpressed that resulted in significantly decreased transcript levels of all of the predicted targets in human, i.e., EXOC7, RAD9A, and TFE3 in the virus-infected cells. The analysis showed that the immune response and cytoskeleton organization are two of the most notable biological processes regulated by the infection-modulated miRNAs. Additionally, the genomic mutation of SARS-CoV-2 contributed to the changed miRNA repository and targets, suggesting a possible role of miRNAs in the attenuated phenotype of SARS-CoV-2 during its evolution. This study provided a comprehensive view of the miRNA-involved regulatory system during SARS-CoV-2 infection, indicating possible antiviral therapeutics against SARS-CoV-2 through intervening miRNA regulation.
Suppressed estrogen supply via extra-ovarian progesterone receptor membrane component 1 in menopause
J Biomed Res 2021, 35(3): 228-237.
doi: 10.7555/JBR.35.20200172
In post-menopausal women, intra-mammary estrogen, which is converted from extra-ovarian estrone (E1), promotes the growth of breast cancer. Since the aromatase inhibitor letrozole does not suppress 17β-estradiol (E2) production from E1, high intra-mammary E1 concentrations impair letrozole's therapeutic efficacy. Progesterone receptor membrane component 1 (Pgrmc1) is a non-classical progesterone receptor associated with breast cancer progression. In the present study, we introduced a Pgrmc1 heterozygous knockout (hetero KO) murine model exhibiting low Pgrmc1 expression, and observed estrogen levels and steroidogenic gene expression. Naïve Pgrmc1 hetero KO mice exhibited low estrogen (E2 and E1) levels and low progesterone receptor (PR) expression, compared to wild-type mice. In contrast, Pgrmc1 hetero KO mice that have been ovariectomized (OVX), including letrozole-treated OVX mice (OVX-letrozole), exhibited high estrogen levels and PR expression. Increased extra-ovarian estrogen production in Pgrmc1 hetero KO mice was observed with the induction of steroid sulfatase (STS). In MCF-7 cell, letrozole suppressed PR expression, but PGRMC1 knockdown increased PR and STS expression. Our presented results highlight the important role of Pgrmc1 in modulating estrogen production when ovary-derived estrogen is limited, thereby suggesting a potential therapeutic approach for letrozole resistance.
J Biomed Res 2021, 35(3): 238-246.
doi: 10.7555/JBR.34.20200074
Arrhythmias are very common in the healthy populations as well as patients with cardiovascular diseases. Among them, atrial fibrillation (AF) and malignant ventricular arrhythmias are usually associated with some clinical events. Early diagnosis of arrhythmias, particularly AF and ventricular arrhythmias, is very important for the treatment and prognosis of patients. Holter is a gold standard commonly recommended for noninvasive detection of paroxysmal arrhythmia. However, it has some shortcomings such as fixed detection timings, delayed report and inability of remote real-time detection. To deal with such problems, we designed and applied a new wearable 72-hour triple-lead H3-electrocardiogram (ECG) device with a remote cloud-based ECG platform and an expert-supporting system. In this study, 31 patients were recruited and 24-hour synchronous ECG data by H3-ECG and Holter were recorded. In the H3-ECG group, ECG signals were transmitted using remote real-time modes, and confirmed reports were made by doctors in the remote expert-supporting system, while the traditional modes and detection systems were used in the Holter group. The results showed no significant differences between the two groups in 24-hour total heart rate (HR), averaged HR, maximum HR, minimum HR, premature atrial complexes (PACs) and premature ventricular complexes (PVCs) (P>0.05). The sensitivity and specificity of capture and remote automatic cardiac events detection of PACs, PVCs, and AF by H3-ECG were 93% and 99%, 98% and 99%, 94% and 98%, respectively. Therefore, the long-term limb triple-lead H3-ECG device can be utilized for domiciliary ECG self-monitoring and remote management of patients with common arrhythmia under medical supervision.
J Biomed Res 2021, 35(3): 247-252.
doi: 10.7555/JBR.34.20200079
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Authors and Reviewers
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