• ISSN 1674-8301
  • CN 32-1810/R
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).
Obesity is an escalating global pandemic posing 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.
Arrhythmias are very common in healthy population 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-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 H3-ECG group, the 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 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.
There is growing evidence that cellular metabolism can directly participate in epigenetic dynamics and consequently modulate gene expression. However, the role of metabolites in activating the key gene regulatory network for specialization of germ cell lineage remains largely unknown. Here, we identified some cellular metabolites with significant changes by untargeted metabolomics between mouse epiblast-like cells (EpiLCs) and primordial germ cell-like cells (PGCLCs). More importantly, we found that inhibition of glutaminolysis by bis-2- (5-phenylacetamido-1,3,4-thiadiazol-2-yl)ethyl sulfide (BPTES) impeded PGCLC specialization, but the impediment could be rescued by addition of α-ketoglutarate (αKG), the intermediate metabolite of oxidative phosphorylation and glutaminolysis. Moreover, adding αKG alone to the PGCLC medium accelerated the PGCLC specialization through promoting H3K27me3 demethylation. Thus, our study reveals the importance of metabolite αKG in the germ cell fate determination and highlights the essential role of cellular metabolism in shaping the cell identities through epigenetic events.
Genome editing has undergone rapid development in recent years, yielding new approaches to make precise changes in genes. In this review, we discuss the development of various adenine and cytosine base-editing technologies, which share the ability to make specific base changes at specific sites in the genome. We also describe multiple applications of base editing in vitro and in vivo. Finally, as a practical example, we demonstrate the use of a cytosine base editor and an adenine base editor in human cells to introduce and then correct a prevalent mutation responsible for hereditary tyrosinemia type 1.
The rabbit has been recognized as a valuable model in various biomedical and biological research fields because of its intermediate size and phylogenetic proximity to primates. However, the technology for precise genome manipulations in rabbit has been stalled for decades, severely limiting its applications in biomedical research. Novel genome editing technologies, especially CRISPR/Cas9, have remarkably enhanced precise genome manipulation in rabbits, and shown their superiority and promise for generating rabbit models of human genetic diseases. In this review, we summarize the brief history of transgenic rabbit technology and the development of novel genome editing technologies in rabbits.
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--2020, 34(6)
Editorial Commentary
This special issue of The Journal of Biomedical Research presents rigorous empirical analysis related to COVID-19 research in responding to the current global COVID-19 pandemic. Selected articles from different disciplines not only offer broader perspectives on combating the outbreaks, but also disseminate the most updated findings on this new challenge for human being to the field.
Review Article
The Balanced Budget Act of 1997 created a designation for critical access hospitals (CAHs) to sustain care for people living in rural communities who lacked access to care due to hospital closures over the preceding decade. Twenty-five years later, 1350 CAHs serve approximately 18% of the US population and a systematic policy evaluation has yet to be performed. This policy analysis serves to define challenges faced by CAHs through a literature review addressing the four major categories of payment, quality, access to capital, and workforce. Additionally, this analysis describes how current challenges to maintain sustainability of CAHs over time are accentuated by gaps in public health infrastructure and variability in individual health care plans exhibited during the COVID-19 pandemic.
Measuring virus-specific antibody responses to emerging pathogens is a well-established and highly useful tool to diagnose such infections, understand interactions between the immune system and pathogens, and provide potential clues for the development of vaccines or therapeutic agents against such pathogens. Since the beginning of 2020, the discovery of SARS-CoV-2 as the emerging virus responsible for the COVID-19 pandemic has provided new insight into the complexity of antibody responses to this dangerous virus. The current review aims to sort out diverse and sometimes seemingly confusing findings to put together a cohesive understanding on the profile of antibody responses elicited in COVID-19 patients.
The start of the global pandemic secondary to the novel SARS-CoV-2 virus was a time of uncertainty and fear as it claimed the lives of many across the world. Since then, there has been a plethora of research designs and trials in order to understand what we can do to stop the spread of the disease. Scientists and health care providers have utilized old medications and revamped them for current use such a convalescent plasma and steroids, as well as creating novel therapeutics, some with promising results. In this article, we review the major therapeutic options currently available and look into what the future still holds in order to further our understanding of this mysterious disease.
The outbreak and rapid spread of COVID-19 has become a public health emergency of international concern. A number of studies have used modeling techniques and developed dynamic models to estimate the epidemiological parameters, explore and project the trends of the COVID-19, and assess the effects of intervention or control measures. We identified 63 studies and summarized the three aspects of these studies: epidemiological parameters estimation, trend prediction, and control measure evaluation. Despite the discrepancy between the predictions and the actuals, the dynamic model has made great contributions in the above three aspects. The most important role of dynamic models is exploring possibilities rather than making strong predictions about longer-term disease dynamics.
Original Article
We sought to determine the characteristics of viral specimens associated with fatal cases, asymptomatic cases and non-fatal symptomatic cases of COVID-19. This included the analysis of 1264 specimens found reactive for at least two SARS-CoV-2 specific loci from people screened for infection in Northern Nevada in March-May of 2020. Of these, 30 were specimens from fatal cases, while 23 were from positive, asymptomatic cases. We assessed the relative amounts of SARS-CoV-2 RNA from sample swabs by real-time PCR and use of the threshold crossing value (Ct). Moreover, we compared the amount of human RNase P found on the same swabs. A considerably higher viral load was found to be associated with swabs from cases involving fatality and the difference was found to be strongly statistically significant. Noting this difference, we sought to assess whether any genetic correlation could be found in association with virus from fatal cases using whole genome sequencing. While no common genetic elements were discerned, one branch of epidemiologically linked fatal cases did have two point mutations, which no other of 156 sequenced cases from northern Nevada had. The mutations caused amino acid changes in the 3′-5′ exonuclease protein, and the product of the gene, orf8.
Many studies have investigated causes of COVID-19 and explored safety measures for preventing COVID-19 infections. Unfortunately, these studies fell short to address disparities in health status and resources among decentralized communities in the United States. In this study, we utilized an advanced modeling technique to examine complex associations of county-level health factors with COVID-19 mortality for all 3141 counties in the United States. Our results indicated that counties with more uninsured people, more housing problems, more urbanized areas, and longer commute are more likely to have higher COVID-19 mortality. Based on the nationwide population-based data, this study also echoed prior research that used local data, and confirmed that county-level sociodemographic factors, such as more Black, Hispanic, and older subpopulations, are attributed to high risk of COVID-19 mortality. We hope that these findings will help set up priorities on high risk communities and subpopulations in future for fighting the novel virus.
We compared subgroup differences in COVID-19 case and mortality and investigated factors associated with case and mortality rate (MR) measured at the county level in Mississippi. Findings were based on data published by the Mississippi State Department of Health between March 11 and July 16, 2020. The COVID-19 case rate and case fatality rate (CFR) differed by gender and race, while MR only differed by race. Residents aged 80 years or older and those who live in a non-metro area had a higher case rate, CFR, and MR. After controlling for selected factors, researchers found that the percent of residents who are obese, low income, or with certain chronic conditions were associated with the county COVID-19 case rate, CFR, and/or MR, though some were negatively related. The findings may help the state to identify counties with higher COVID-19 case rate, CFR, and MR based on county demographics and the degree of its chronic conditions.
Global prevalence of coronavirus disease 2019 (COVID-19) calls for an urgent development of anti-viral regime. Compared with the development of new drugs, drug repurposing can significantly reduce the cost, time, and safety risks. Given the fact that coronavirus harnesses spike protein to invade host cells through angiotensin-converting enzyme 2 (ACE2), hence we see if any previous anti-virtual compounds can block spike-ACE2 interaction and inhibit the virus entry. The results of molecular docking and molecular dynamic simulations revealed that remdesivir exhibits better than expected anti-viral invasion potential against COVID-19 among the three types of compounds including remdesivir, tenofovir and lopinavir. In addition, a positive correlation between the surface area occupied by remdesivir and anti-viral invasion potential was also found. As such, the structure of remdesivir was modified by linking an N-benzyl substituted diamidine derivative to its hydroxyl group through an ester bond. It was found that this compound has a higher anti-viral invasion potential and greater specificity.
Case Report
The ongoing coronavirus disease 2019 (COVID-19) pandemic is a global public health crisis, causing social and economic disasters in many countries. In China, two-consecutive negative results of nucleic acid tests for SARS-CoV-2 from the respiratory samples are required to end the quarantine of COVID-19 patients. However, clinicians face a dilemma in case of patients with long-term viral shedding. This report described an unusual COVID-19 case who had persistent viral RNA positivity for more than 4 months after initial illness in the presence of low neutralizing antibodies, but without prolonged clinical symptoms. Multiple anti-viral drug treatments had no impact and there was no evidence of re-infection. When the patient was self-quarantined at home, no infection occurred to the three family members living with her for 15 to 19 days. Sputum viral culture in BSL-3 laboratory on the 102nd day after symptom onset was negative. From the 129th day on, 8 continuous nucleic acid tests of sputum samples showed negative results. The patient was discharged on 137th days since symptom onset. In conclusion, viral RNA shedding in the sputum of the COVID-19 patient may last over 4 months. As no evidence shows the existence of infectious virus, two-consecutive negative nucleic acid tests may not be the prerequisite for ending quarantine of COVID-19 patients with prolonged viral shedding.
The MDM2-p53 pathway revisited
Subhasree Nag, Jiangjiang Qin, Kalkunte S. Srivenugopal, Minghai Wang, Ruiwen Zhang
2013, 27(4): 254-271.   doi: 10.7555/JBR.27.20130030
+Abstract PDF 1738KB
Current perspectives of nanoparticles in medical and dental biomaterials
Ibrahim Mohamed Hamouda
2012, 26(3): 143-151.   doi: 10.7555/JBR.26.20120027
+Abstract PDF 588KB
A retrospective analysis of the safety and efficacy of low dose tacrolimus (FK506) for living donor liver transplant recipients
Zhengshan Wu, Qingyang Meng, Yongxiang Xia, Feng Zhang, Wei You
2013, 27(4): 305-309.   doi: 10.7555/JBR.27.20130023
+Abstract PDF 1225KB
Myocardin in biology and disease
Joseph M. Miano
2015, 29(1): 3-19.   doi: 10.7555/JBR. 29.20140151
+Abstract PDF 5076KB
Cryptosporidiosis-an overview
Gordon J Leitch, Qing He
2011, 25(1): 1-16.   doi: 10.1016/S1674-8301(11)60001-8
+Abstract PDF 985KB
GYY4137 protects against myocardial ischemia and reperfusion injury by attenuating oxidative stress and apoptosis in rats
Guoliang Meng, Jing Wang, Yujiao Xiao, Wenli Bai, Liping Xie, Liyang Shan, Philip K Moore, Yong Ji
2015, 29(3): 203-213.   doi: 10.7555/JBR.28.20140037
+Abstract PDF 2347KB
Low dose bisphenol A impairs spermatogenesis by suppressing reproductive hormone production and promoting germ cell apoptosis in adult rats
Pengpeng Jin, Xiaoli Wang, Fei Chang, Yinyang Bai, Yingchun Li, Rong Zhou, Ling Chen
2013, 27(2): 135-144.   doi: 10.7555/JBR.27.20120076
+Abstract PDF 1389KB
Sox2 enhances the tumorigenicity and chemoresistance of cancer stem-like cells derived from gastric cancer
Tian Tian, Yajie Zhang, Shouyu Wang, Jianwei Zhou, Shan Xua
2012, 26(5): 336-345.   doi: 10.7555/JBR.26.20120045
+Abstract PDF 3577KB
Emerging roles of cardiolipin remodeling in mitochondrial dysfunction associated with diabetes, obesity, and cardiovascular diseases
Yuguang Shi
2010, 24(1): 6-15.  
+Abstract PDF 407KB
Development of Leishmania vaccines: predicting the future from past and present experience
Joshua Muli Mutiso, John Chege Macharia, Maria Ndunge Kiio, James Maina Ichagichu, Hitler Rikoi, Michael Muita Gicheru
2013, 27(2): 85-102.   doi: 10.7555/JBR.27.20120064
+Abstract PDF 1050KB
Class A scavenger receptor activation inhibits endoplasmic reticulum stress-induced autophagy in macrophage
Hanpeng Huang, Xiaoyu Li, Yan Zhuang, Nan Li, Xudong Zhu, Jin Hu, Jingjing Ben, Qing Yang, Hui Bai, Qi Chen
2014, 28(3): 213-221.   doi: 10.7555/JBR.28.20130105
+Abstract [PDF 11939KB](653)
Dual therapy of rosiglitazone/pioglitazone with glimepiride on diabetic nephropathy in experimentally induced type 2 diabetes rats
Ravi Prakash Rao, Ansima Singh, Arun K Jain, Bhartu Parsharthi Srinivasan
2011, 25(6): 411-417.   doi: 10.1016/S1674-8301(11)60054-7
+Abstract [PDF 1947KB](652)
A clinical perspective on mucoadhesive buccal drug delivery systems
Ritu MGilhotra, Mohd Ikram, Sunny Srivastava, Neeraj Gilhotra
2014, 28(2): 81-97.   doi: 10.7555/JBR.27.20120136
+Abstract [PDF 2323KB](665)
AEG-1 expression correlates with CD133 and PPP6c levels in human glioma tissues
Jia Guo, Xin Chen, Ruxing Xi, Yuwei Chang, Xuanwei Zhang, Xiaozhi Zhang
2014, 28(5): 388-395.   doi: 10.7555/JBR.28.20140015
+Abstract [PDF 14254KB](673)
Lipoprotein metabolism in nonalcoholic fatty liver disease
Zhenghui Gordon Jiang, Simon C. Robson, Zemin Yao
2013, 27(1): 1-13.   doi: 10.7555/JBR.27.20120077
+Abstract [PDF 1247KB](661)
ApoB/apoA1 is an effective predictor of coronary heart disease risk in overweight and obesity
Min Lu, Qun Lu, Yong Zhang, Gang Tian
2011, 25(4): 266-273.   doi: 10.1016/S1674-8301(11)60036-5
+Abstract [PDF 1144KB](647)
Development of Leishmania vaccines: predicting the future from past and present experience
Joshua Muli Mutiso, John Chege Macharia, Maria Ndunge Kiio, James Maina Ichagichu, Hitler Rikoi, Michael Muita Gicheru
2013, 27(2): 85-102.   doi: 10.7555/JBR.27.20120064
+Abstract [PDF 1050KB](667)
Atrial fibrillation
Thomas M. Munger, Li-Qun Wu, Win K. Shen
2014, 28(1): 1-17.   doi: 10.7555/JBR.28.20130191
+Abstract [PDF 5352KB](677)
Maternal risk factors for low birth weight for term births in a developed region in China: a hospital-based study of 55,633 pregnancies
Yihua Bian, Zhan Zhang, Qiao Liu, Di Wu, Shoulin Wang
2013, 27(1): 14-22.   doi: 10.7555/JBR.27.20120046
+Abstract [PDF 1263KB](659)
Fracture resistance of posterior teeth restored with modern restorative materials
Ibrahim M. Hamouda, Salah H. Shehata
2011, 25(6): 418-424.   doi: 10.1016/S1674-8301(11)60055-9
+Abstract [PDF 763KB](644)