{"title":"Antitumor and off-target effects of cholesterol-conjugated let-7a mimics in an orthotopic hepatocellular carcinoma xenograft nude mouse model.","authors":"Jian Guan, Mingyang Liu, Xin Li, Liangrui Zhou, Xueyu Dong, Wei Dai, Yu Xia, Tao Yang, Shaojuan Guo, Xingqi Li, Yehua Han, Yufeng Luo","doi":"10.1097/JBR.0000000000000103","DOIUrl":"https://doi.org/10.1097/JBR.0000000000000103","url":null,"abstract":"<p><p>To explore the antitumor and potential off-target effects of systemically delivered cholesterol-conjugated <i>let-7a</i> mimics <i>(Chol-let-7a</i>) and control mimics <i>(Chol-miRCtrl</i>) on hepatocellular carcinoma <i>in vivo.</i></p><p><strong>Methods: </strong>The antitumor effects of two intravenous dosing regimens of <i>Chol-let-7a</i> on heptocellular carcinoma growth were compared using an orthotopic xenograft mouse model. Off-targets were analyzed with histopathological and ultrapathological features of heparenal tissue and cells in the <i>Chol-let-7a-, Chol-miRCtrl-</i>, and saline-treated (blank) xenograft mice and normal control mice. Then, <i>let-7</i>a abundance in orthotopic tumors, corresponding paracancerous hepatic tissue, and normal liver tissue from healthy nude mice was examined by reverse transcription-polymerase chain reaction. The distribution of <i>Chol-let-7a</i> and <i>Chol-miRCtrl in vivo</i> was examined by whole-animal imaging and frozen-sections observation. The experiments were approved by the Institutional Research Board of Peking Union Medical College Hospital.</p><p><strong>Results: </strong>Continuous treatment with <i>Chol-let-7a</i> resulted in tumors that were 35.86% and 40.02% the size of those in the <i>Chol-miRCtrl</i> and blank xenograft group (<i>P <</i> 0.01 and <i>P</i> < 0.01, respectively), while intermittent dosing with <i>Chol-let-7a</i> resulted in tumors that were 65.42% and 56.66% the size of those in the <i>Chol-miRCtrl</i> and the blank control group, respectively (<i>P</i> < 0.05 and <i>P <</i> 0.05). In addition, some histopathological and ultrapathological features were only observed after treatment with the two cholesterol-conjugated molecules, however mild with intermittent dosing <i>Chol-let-7a</i> treatment, such as diffuse sinusoidal dilation and edema, primarily around the centrolobular vein in heptic tissues; mild hypercellularity with dilated capillary lumens in the renal tissue; and some organelle abnormalities found in heptic and renal cells. Furthermore, whole-animal imaging showed that <i>Chol-let-7a</i> and <i>Chol-miRCtrl</i> were predominantly distributed in the liver, kidney, and bladder regions after injection, and that the concentration of <i>Chol-let-7a</i> and <i>Chol-miRCtrl</i> in the kidney and the bladder decreased much slowly in the xenograft animals, especially in the <i>Chol-miRCtrl</i> group. Finally, RT-PCR analysis showed that <i>let-7a</i> levels were significantly increased in Chol-let-7a-treated xenografts compared with <i>Chol-miRCtrl</i> group (<i>P</i>=0.003) and blank xenograft group (<i>P</i>=0.001); however, the level was only equivalent to 50.6% and 40.7% of that in paracancerous hepatic tissue and hepatic tissue in normal mice, respectively.</p><p><strong>Conclusions: </strong><i>Chol-let-7a</i>, administered either continuously or intermittently, showed effective antitumor efficacy. <i>Chol-let-7a</i> had some off-target effects, such as mil","PeriodicalId":33885,"journal":{"name":"Journal of BioX Research","volume":"5 4","pages":"181-196"},"PeriodicalIF":0.0,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/4d/75/jr9-5-181.PMC9810003.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10512840","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Journal of BioX ResearchPub Date : 2022-09-01Epub Date: 2022-08-29DOI: 10.1097/JBR.0000000000000125
Elizabeth Rao, Payal Grover, Hongtao Zhang
{"title":"Thrombosis after SARS-CoV2 infection or COVID-19 vaccination: will a nonpathologic anti-PF4 antibody be a solution?-A narrative review.","authors":"Elizabeth Rao, Payal Grover, Hongtao Zhang","doi":"10.1097/JBR.0000000000000125","DOIUrl":"https://doi.org/10.1097/JBR.0000000000000125","url":null,"abstract":"<p><p>The coronavirus disease 2019 (COVID-19) pandemic was triggered by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a previously unknown strain of coronavirus. To fully understand the consequences and complications of SARS-CoV-2 infections, we have reviewed current literature on coagulation dysfunctions that are related to the disease and vaccination. While COVID-19 is more commonly considered as a respiratory illness, studies indicate that, in addition to respiratory illness, a coagulation dysfunction may develop in individuals after the initial infection, placing them at the risk of developing thrombotic events. Patients who died of COVID-19 had higher levels of D-dimer, a biomarker for blood clot formation and breakdown. Effective treatments for coagulation dysfunctions are critically needed to improve patient survival. On the other hand, antibodies against platelet factor 4 (PF4)/heparin may be found in patients with rare instances of vaccine-induced immunological thrombotic thrombocytopenia (VITT) following vaccination with adenovirus-based vaccines. VITT is characterized by atypical thrombosis and thrombocytopenia, similar to immune-mediated heparin-induced thrombocytopenia (HIT), but with no need for heparin to trigger the immune response. Although both adenovirus-based and mRNA-based vaccines express the Spike protein of SARS-CoV-2, VITT is exclusively related to adenovirus-based vaccines. Due to the resemblance with HIT, the use of heparin is highly discouraged against treating patients with thrombotic thrombocytopenia after SARS-CoV-2 infection or with VITT after vaccination. Intravenous immunoglobulin therapy coupled with anticoagulation is recommended instead. The well-studied anti-PF4 monoclonal antibody RTO, which does not induce pathologic immune complexes in the presence of heparin and has been humanized for a potential treatment modality for HIT, may provide a nonanticoagulant HIT-specific solution to the problem of increased blood coagulation after SARS-CoV-2 infection or the VITT after immunization.</p>","PeriodicalId":33885,"journal":{"name":"Journal of BioX Research","volume":"5 3","pages":"97-103"},"PeriodicalIF":0.0,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/d8/7e/jr9-5-97.PMC9531924.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33497265","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Journal of BioX ResearchPub Date : 2022-09-01Epub Date: 2022-10-03DOI: 10.1097/JBR.0000000000000129
{"title":"Corrigendum: <i>In vivo</i> detection of metabolic <sup>2</sup>H-incorporation upon ingestion of <sup>2</sup>H<sub>2</sub>O.","authors":"","doi":"10.1097/JBR.0000000000000129","DOIUrl":"10.1097/JBR.0000000000000129","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.1097/JBR.0000000000000121.].</p>","PeriodicalId":33885,"journal":{"name":"Journal of BioX Research","volume":"5 3","pages":"141"},"PeriodicalIF":0.0,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/c6/fd/jr9-5-141.PMC9531977.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33538799","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Journal of BioX ResearchPub Date : 2022-03-01Epub Date: 2021-12-09DOI: 10.1097/JBR.0000000000000119
{"title":"Corrigendum: <i>PA1426</i> regulates <i>Pseudomonas aeruginosa</i> quorum sensing and virulence: an in vitro study.","authors":"","doi":"10.1097/JBR.0000000000000119","DOIUrl":"10.1097/JBR.0000000000000119","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.1097/JBR.0000000000000088.].</p>","PeriodicalId":33885,"journal":{"name":"Journal of BioX Research","volume":"5 1","pages":"47"},"PeriodicalIF":0.0,"publicationDate":"2022-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/2b/97/jr9-5-47.PMC9394490.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33445504","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Journal of BioX ResearchPub Date : 2021-06-01Epub Date: 2020-12-03DOI: 10.1097/JBR.0000000000000076
Song Fan, Qi Zhen, Cheng Chen, Wenjun Wang, Qibing Wu, Huihui Ma, Chengyuan Zhang, Li Zhang, Baojing Lu, Huiyao Ge, Liang Yong, Bao Li, Yafen Yu, Weiwei Chen, Yiwen Mao, Guangbo Qu, Li Su, Aoli Wang, Zhen Ding, Haiwen Li, Jin Zhang, Yonglian Wang, Yufeng Gao, Xihai Xu, Zhongming Zhu, Jun Chen, Long Zhang, Hongqiang Liang, Song Wu, Meng Huang, Quan Xia, Ping Li, Yehuan Sun, Chaozhao Liang, Wei Wei, Qingsong Liu, Liangdan Sun
{"title":"Clinical efficacy of low-dose emetine for patients with COVID-19: a real-world study.","authors":"Song Fan, Qi Zhen, Cheng Chen, Wenjun Wang, Qibing Wu, Huihui Ma, Chengyuan Zhang, Li Zhang, Baojing Lu, Huiyao Ge, Liang Yong, Bao Li, Yafen Yu, Weiwei Chen, Yiwen Mao, Guangbo Qu, Li Su, Aoli Wang, Zhen Ding, Haiwen Li, Jin Zhang, Yonglian Wang, Yufeng Gao, Xihai Xu, Zhongming Zhu, Jun Chen, Long Zhang, Hongqiang Liang, Song Wu, Meng Huang, Quan Xia, Ping Li, Yehuan Sun, Chaozhao Liang, Wei Wei, Qingsong Liu, Liangdan Sun","doi":"10.1097/JBR.0000000000000076","DOIUrl":"https://doi.org/10.1097/JBR.0000000000000076","url":null,"abstract":"<p><strong>Objective: </strong>Emetine, an isoquinoline alkaloid that is enriched at high concentrations in the lung, has shown potent in vitro activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The aim of this study was to better understand the effectiveness of low-dose emetine for patients with coronavirus disease 2019 (COVID-19).</p><p><strong>Methods: </strong>In this real-world study, 63 patients with mild or common COVID-19 were recruited from Wuhan Fangcang Shelter Hospital and five COVID-19-designated hospitals in Anhui Province, China from February to March 2020. Thirty-nine patients from Wuhan Fangcang Shelter Hospital were assigned to a pragmatic randomized controlled clinical trial, and 24 patients from the 5 COVID-19-designated hospitals in Anhui Province underwent a real-world study. The medication course of emetine was less than 10 days. The main symptoms and adverse reactions of all patients were observed and recorded. The primary outcome measure was the time required for a negative SARS-CoV-2 RNA result or the negative result rate on day 10. Secondary outcomes included axillary temperature, transcutaneous oxygen saturation, and respiratory frequency recovery. The study was approved by the Ethics Committee of The First Affiliated Hospital of Anhui Medical University on February 20, 2019 (approval No. PJ2020-03-19) and was registered with the Chinese Clinical Trial Registry on February 20, 2019 (registration number: ChiCTR2000030022).</p><p><strong>Results: </strong>The oxygen saturation values were higher in the treatment group than in the control group on the first day after enrollment for patients treated at Fangcang Shelter Hospital. The axillary body temperature, respiratory rate, and oxygen saturation among patients in Fangcang Shelter Hospital were related to the time effect but not to the intervention measures. The respiratory rate and oxygen saturation of patients in the Anhui designated hospitals were related to the intervention measures but not to the time effect. The axillary body temperature of patients in Anhui designated hospitals was related to the time effect but not to the intervention measures.</p><p><strong>Conclusion: </strong>Our preliminary study shows that low-dose emetine combined with basic conventional antiviral drugs improves clinical symptoms in patients with mild and common COVID-19 without apparent adverse effects, suggesting that moderately increased doses of emetine may have good potential for treatment and prevention of COVID-19.</p>","PeriodicalId":33885,"journal":{"name":"Journal of BioX Research","volume":"4 2","pages":"53-59"},"PeriodicalIF":0.0,"publicationDate":"2021-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/9e/64/jr9-4-53.PMC8237841.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39178171","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Journal of BioX ResearchPub Date : 2021-06-01Epub Date: 2021-05-25DOI: 10.1097/JBR.0000000000000098
Lei Cai, Lin He
{"title":"The novel coronavirus and humans: who can dominate who?","authors":"Lei Cai, Lin He","doi":"10.1097/JBR.0000000000000098","DOIUrl":"https://doi.org/10.1097/JBR.0000000000000098","url":null,"abstract":"Life may have first arisen on Earth billions of years ago in the form of viruses, which have had a significant influence on the evolution of all living creatures, including human beings. Some scientists believe that up to 8% of the human genome is derived from viruses, which are simple, primitive organisms with a variety of different shapes and sizes. Countless undiscovered viruses can exist within the human body and co-evolve with human beings. Some are pathogenic, but most do not harm humans. The human body is such a complex organism system that it can host bacteria, fungi, and viruses; humans can also engage in high-level thinking and create civilizations. In contrast, viruses are such simple organisms that they consist solely of genetic material (DNA or RNA) and a protective protein capsid, and as such are often overlooked. Both viruses and humans evolve to adapt to changes in their environment. Sometimes they are in conflict with each other, while sometimes they coexist peacefully. However, new conflicts between viruses and humans always arise, which begs the question of who will win: humans or viruses? Several viral pandemics have affected humans over the course of history, such as the influenza pandemic of 1918, severe acute respiratory syndrome (SARS) in 2003, bird flu in 2013, Ebola in 2014, and the novel coronavirus in 2019. Humans have never succumbed to these viruses, but have risen to the challenge of combatting them, including the novel coronavirus. The novel coronavirus is less lethal than smallpox and Ebola but is extremely infectious. Moreover, it has a single-stranded RNA genome, which makes it particularly likely to acquire mutations during a large-scale epidemic. The coronavirus disease 2019 (COVID-19) pandemic has done considerable damage to the human world. Prof. He, a renowned and brilliant geneticist, has made the following comments","PeriodicalId":33885,"journal":{"name":"Journal of BioX Research","volume":"4 2","pages":"45"},"PeriodicalIF":0.0,"publicationDate":"2021-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/b1/14/jr9-4-45.PMC8237838.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39178169","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Connor L West, Austin C V Doughty, Kaili Liu, Wei R Chen
{"title":"Monitoring tissue temperature during photothermal therapy for cancer.","authors":"Connor L West, Austin C V Doughty, Kaili Liu, Wei R Chen","doi":"10.1097/jbr.0000000000000050","DOIUrl":"https://doi.org/10.1097/jbr.0000000000000050","url":null,"abstract":"<p><p>Phototherapies offer promising alternatives to traditional cancer therapies. Phototherapies mainly rely on manipulation of target tissue through photothermal, photochemical, or photomechanical interactions. Combining phototherapy with immunotherapy has the benefit of eliciting a systemic immune response. Specifically, photothermal therapy (PTT) has been shown to induce apoptosis and necrosis in cancer cells, releasing tumor associated antigenic peptides while sparing healthy host cells, through temperature increase in targeted tissue. However, the tissue temperature must be monitored and controlled to minimize adverse thermal effects on normal tissue and to avoid the destruction of tumor-specific antigens, in order to achieve the desired therapeutic effects of PTT. Techniques for monitoring PTT have evolved from post-treatment quantification methods like enzyme linked immunosorbent assay, western blot analysis, and flow cytometry to modern methods capable of real-time monitoring, such as magnetic resonance thermometry, computed tomography, and photoacoustic imaging. Monitoring methods are largely chosen based on the type of light delivery to the target tissue. Interstitial methods of thermometry, such as thermocouples and fiber-optic sensors, are able to monitor temperature of the local tumor environment. However, these methods can be challenging if the phototherapy itself is interstitially administered. Increasingly, non-invasive therapies call for non-invasive monitoring, which can be achieved through magnetic resonance thermometry, computed tomography, and photoacoustic imaging techniques. The purpose of this review is to introduce the feasible methods used to monitor tissue temperature during PTT. The descriptions of different techniques and the measurement examples can help the researchers and practitioners when using therapeutic PTT.</p>","PeriodicalId":33885,"journal":{"name":"Journal of BioX Research","volume":"2 4","pages":"159-168"},"PeriodicalIF":0.0,"publicationDate":"2019-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1097/jbr.0000000000000050","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38515060","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Zhipeng Liu, Naga Chalasani, Jingmei Lin, Samer Gawrieh, Yuan He, Yan J Tseng, Wanqing Liu
{"title":"Integrative omics analysis identifies macrophage migration inhibitory factor signaling pathways underlying human hepatic fibrogenesis and fibrosis.","authors":"Zhipeng Liu, Naga Chalasani, Jingmei Lin, Samer Gawrieh, Yuan He, Yan J Tseng, Wanqing Liu","doi":"10.1097/jbr.0000000000000026","DOIUrl":"https://doi.org/10.1097/jbr.0000000000000026","url":null,"abstract":"<p><p>The genetic basis underlying liver fibrosis remains largely unknown. We conducted a study to identify genetic alleles and underlying pathways associated with hepatic fibrogenesis and fibrosis at the genome-wide level in 121 human livers. By accepting a liberal significance level of <i>P</i><1e-4, we identified 73 and 71 candidate loci respectively affecting the variability in alpha-smooth muscle actin (α-SMA) levels (fibrogenesis) and total collagen content (fibrosis). The top genetic loci associated with the two markers were <i>BAZA1</i> and <i>NOL10</i> for α-SMA expression and <i>FAM46A</i> for total collagen content (<i>P</i><1e-6). We further investigated the relationship between the candidate loci and the nearby gene transcription levels (cis-expression quantitative trait loci) in the same liver samples. We found that 44 candidate loci for α-SMA expression and 44 for total collagen content were also associated with the transcription of the nearby genes (<i>P</i><0.05). Pathway analyses of these genes indicated that macrophage migration inhibitory factor (MIF) related pathway is significantly associated with fibrogenesis and fibrosis, though different genes were enriched for each marker. The association between the single nucleotide polymorphisms, MIF and α-SMA showed that decreased MIF expression is correlated with increased α-SMA expression, suggesting that variations in MIF locus might affect the susceptibility of fibrogenesis through controlling MIF gene expression. In summary, our study identified candidate alleles and pathways underlying both fibrogenesis and fibrosis in human livers. Our bioinformatics analyses suggested MIF pathway as a strong candidate involved in liver fibrosis, thus further investigation for the role of the MIF pathway in liver fibrosis is warranted. The study was reviewed and approved by the Institutional Review Board (IRB) of Wayne State University (approval No. 201842) on May 17, 2018.</p>","PeriodicalId":33885,"journal":{"name":"Journal of BioX Research","volume":"2 1","pages":"16-24"},"PeriodicalIF":0.0,"publicationDate":"2019-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1097/jbr.0000000000000026","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38399172","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}