• 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).
To investigate feasibility and effectiveness of the establishing porcine ischemia-reperfusion models by ligating the left anterior descending (LAD) coronary artery, we first randomly divided 16 male Bama pigs into a sham group and a model group. After anesthesia, we separated the arteries and veins and passed the LAD coronary artery through a median thoracic incision to be below the beginning of its first diagonal branch. Then, we loosened and released the ligation line after five minutes of pre-occlusion. Finally, we ligated the LAD coronary artery in situ two minutes later and loosened the ligature 60 minutes after ischemia. Compared with the sham group, ECG showed that ST-segment was ?non-significantly? elevated in multiple continuous leads, and UCG showed that EF and FS were significantly lower at one hour and seven days after operation in the model group. Twenty four hours after operation, the cTnT and CK-MB levels significantly increased in the model group than that in the sham group. The hematoxylin and eosin staining showed many inflammatory cells infiltrating the interstitium of the myocardium in the model group but not in the sham group. Masson staining showed a significant increase in infarct size in the ischemia/reperfusion group. All eight pigs in the model group recovered with normal sinus heart rates, and the survival rate was 100%. In conclusion, the method can provide an accurate and stable large animal model for preclinical research of ischemia/reperfusion with a high success rate and homogeneity of the myocardial infarction area.
Although vaccines have been developed, mutations of SARS-CoV-2, especially the dominant B.1.617.2 (delta) strain and B.1.529 (omicron) with more than 30 mutations on its spike protein have caused a significant decline in prophylaxis, calling for the need for drug improvement. Antibodies are drugs preferentially used in infectious diseases and are easy to get from immunized organisms. This study combined molecular modeling and single memory B cell sequencing to have candidate sequences assessed before experiments, which provided a strategy for SARS-CoV-2 neutralizing antibody fabrication. 128 sequences were obtained after sequencing of 196 memory B cells and 42 sequences were left when merging extremely similar ones and discarding incomplete ones followed by homology modeling of the antibody variable region. 13 candidate sequences were expressed, 3 of them were tested positive for RBD recognition and one was confirmed as having broad neutralization against several SARS-CoV-2 variants. Our study successfully obtained a SARS-CoV-2 antibody with broad neutralizing abilities and provided a strategy from single memory B cell BCR sequencing to antibody with computer assistance, which could be referenced in antibody development of emerging infectious disease.
To overcome immune tolerance to cancer, the immune system needs to be exposed to a multi-target action intervention. Here, we investigated the activating effect of CpG oligodeoxynucleotides, mesyl phosphoramidate CpG oligodeoxynucleotides, anti-OX40 antibodies, and OX40 RNA aptamers on major populations of immunocompetent cells ex vivo. Comparative analysis of the antitumor effects of in situ vaccination with CpG oligodeoxynucleotides and anti-OX40 antibodies, as well as several other combinations such as mesyl phosphoramidate CpG oligodeoxynucleotides and OX40 RNA aptamers, were conducted. Antibodies against programmed death 1 (PD1) checkpoint inhibitors or corresponding PD1 DNA aptamers were also added to vaccination regimens for analytical purposes. Four scenarios were considered: a weakly immunogenic Krebs-2 carcinoma grafted in CBA mice; a moderately immunogenic Lewis carcinoma grafted in C57Black mice; and an immunogenic A20 B cell lymphoma or an Erlich carcinoma, grafted in BALB/c mice. Adding anti-PD1 antibodies (CpG+αOX40+αPD1) to in situ vaccinations boosts the antitumor effect. When used instead of antibodies, aptamers also possess antitumor activity, although this effect was less pronounced. The strongest effect across all the tumors was observed in highly immunogenic A20 B cell lymphoma and Erlich carcinoma.
The erythropoietin-producing human hepatocellular A3 (EphA3) is a member of the largest subfamily of tyrosine kinase receptors—Eph receptors. Previous studies showed that EphA3 is associated with tissue development. Recently, we found that the expression of EphA3 is elevated in the hypothalamus of diet-induced obesity (DIO) mice. However, the role of EphA3 in hypothalamic controlled energy metabolism remains unclear. In this study, we demonstrated that deletion of EphA3 in the hypothalamus by CRISPR/Cas9-mediated gene editing promotes obesity in male mice with high fat diet feeding rather than those with normal chow diet feeding. Moreover, deletion of hypothalamic EphA3 promotes high fat diet-induced obesity by increasing food intake and reducing energy expenditure. Knockdown of EphA3 leads to smaller intracellular vesicles in GT1-7 cells. Our study reveals that hypothalamic EphA3 plays important roles in promoting diet-induced obesity.
Sepsis-induced myocardial dysfunction is accompanied primarily by severe sepsis, which is associated with high morbidity and mortality. 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), a reductase, can convert inactive cortisone into metabolically active cortisol. The role of 11β-HSD1 in sepsis-induced myocardial dysfunction remains poorly understood. This study aimed to investigate the effects of 11β-HSD1 in lipopolysaccharide (LPS)-induced mouse model. LPS(10 mg/kg) was administered to wild-type C57BL/6J mice and 11β-HSD1 global knockout mice. Cardiac function was assessed by echocardiography. Transmission electron microscopy and immunohistochemical staining were performed to analyze myocardial mitochondrial injury and record histological changes. The levels of reactive oxygen species and biomarkers of oxidative stress were determined. Polymerase chain reaction analysis, western blot, and immunofluorescent staining were employed to determine the expression of related genes and proteins, respectively. To investigate the role of 11β-HSD1 in sepsis-induced myocardial dysfunction, LPS was used to induce lentivirus-infected neonatal rat ventricular cardiomyocytes. Knockdown of 11β-HSD1 alleviated LPS-induced myocardial mitochondrial injury, oxidative stress, and inflammation, along with improved myocardial function. Furthermore, depletion of 11β-HSD1 promoted the phosphorylation of adenosine 5'‐monophosphate-activated protein kinase, peroxisome proliferator activated receptor gamma coactivator 1α, and silent information regulator 1 protein levels both in vivo and in vitro. The suppression of 11β-HSD1 may be a viable strategy to improve cardiac function against endotoxemia challenges.
Circulating tumor cells (CTCs) play an important role in tumor metastases, which positively correlates with an increased risk of death. Actin-binding proteins, i.e., cofilin (CFL1), profilin 1 (PFN1), and adenylate cyclase-associated protein 1 (CAP1) are thought to be involved in tumor cell motility and metastasis, specifically in head and neck squamous cell carcinoma (HNSCC). However, there are currently no published studies of CFL1, PFN1, and CAP1 in CTCs and leukocytes in HNSCC patients. We assessed serum levels of CFL1, PFN1, and CAP1 and the number of CTCs and leukocytes containing these proteins in blood from 31 HNSCC patients (T1–4N0–2M0). Analysis was conducted using flow cytometry and an ELISA kit. We found that CAP1+ CTCs and CAP1+ leukocyte subgroups were prevalent in our HNSCC patient samples, while the prevalence rates of CFL1+ and PFN1+ CTCs was relatively low. Patients with stage T2–4N1–2M0 had CFL1+ and PFN1+ CTCs, and with an elevated PFN1 serum level. In general, PFN1 serum level and the relative number of PFN1+CD326+ CTCs could be valuable prognostic markers for HNSCC metastases. This study is the first to obtain data regarding the contents of ABPs in CTCs, and leukocytes in blood from HNSCC patients. This is also the first to assess the relationship between the number of CTCs subgroups and disease characteristics.
Anti-cancer therapy is often a cause of premature ovarian insufficiency and infertility since the ovarian follicle reserve is extremely sensitive to chemotherapy drugs like cisplatin. Various methods have been explored for fertility preservation in women, especially in prepubertal girls undergoing radiotherapy and chemotherapy because of cancer. In recent years, mesenchymal stem cell-derived exosomes (MSC-exos) have been reported to play an important role in tissue repair and treatment of various diseases. In this study, by using exosomes human umbilical cord-derived from mesenchymal stem cells, we observed that human umbilical cord-derived MSC-exos (hucMSC-exos) after short-term culture improved follicular survival and development while receiving cisplatin treatment. Moreover, the intravenous injection of hucMSC-exos improved ovarian function and ameliorated the inflammatory environment within the ovary. The underlying mechanism of hucMSC-exos on fertility preservation was associated with the down-regulation of p53-related apoptosis and their anti-inflammatory function. Taken together, we proposed that HucMSC-derived exosomes might be a potential approach to improve fertility in women diagnosed with cancer.
Acute myocardial infarction (AMI) and sudden cardiac death (SCD), which are associated with acute cardiac ischemia, are one of the leading causes of death of adults in economically developed countries. The development of new approaches for treatment and prevention of AMI, and SCD remains the highest priority for medicine. A study of the cardiovascular effects of chronic hypoxia (CH) could contribute to the development of these methods. Chronic hypoxia exerts both positive and adverse effects. The positive effects are the infarct-reducing, the vasoprotective, and the antiarrhythmic effects, which can lead to the improvement of cardiac contractility in reperfusion. The adverse effects are pulmonary hypertension and right ventricular hypertrophy. This review presents a comprehensive overview of how CH enhances cardiac tolerance to ischemia/reperfusion. It is an in-depth analysis of the published data on the underlying mechanisms which can lead to the development of the cardioprotective effect of CH. A study of the CH-activated protective signaling pathways could contribute to a better understanding of the development of CH as well as could promote the development of new therapeutic approaches in an increase of cardiac tolerance to ischemia/reperfusion.
The Journal of Biomedical Research--2023, 37(2)
Review Article
Sirtuin 3 (SIRT3), the main family member of mitochondrial deacetylase, targets the majority of substrates controlling mitochondrial biogenesis via lysine deacetylation and modulates important cellular functions such as energy metabolism, reactive oxygen species production and clearance, oxidative stress, and aging. Deletion of SIRT3 has a deleterious effect on mitochondrial biogenesis, thus leading to the defect in mitochondrial function and insufficient ATP production. Imbalance of mitochondrial dynamics leads to excessive mitochondrial biogenesis, dampening mitochondrial function. Mitochondrial dysfunction plays an important role in several diseases related to aging, such as cardiovascular disease, cancer and neurodegenerative diseases. Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α) launches mitochondrial biogenesis through activating nuclear respiratory factors. These factors act on genes, transcribing and translating mitochondrial DNA to generate new mitochondria. PGC1α builds a bridge between SIRT3 and mitochondrial biogenesis. This review described the involvement of SIRT3 and mitochondrial dynamics, particularly mitochondrial biogenesis in aging-related diseases, and further illustrated the role of the signaling events between SIRT3 and mitochondrial biogenesis in the pathological process of aging-related diseases.
Circular RNAs (circRNAs) are characterized by a covalent closed-loop structure with an absence of both 5′ cap structure and 3′ polyadenylated tail. Numerous studies have found that circRNAs play an important role in various diseases and have a variety of biological regulatory mechanisms, including acting as microRNA sponges, interacting with proteins, modulating the expression of related genes and translating into peptides or proteins. CircRNAs have also been used as biomarkers for a number of diseases, which could improve clinical practice. This review summarizes the most recent advances in biogenesis and knowledge of the biological functions of circRNAs as well as the related bioinformatics databases. We specifically describe developments in understanding of circRNA functions in the field of environmental exposure-induced diseases. Finally, we focus on potential clinical implications of circRNAs to facilitate their clinical transformation into disease treatment.
Original Article
Lead (Pb) and furan are toxic agents, and persistent exposure may impair human and animal reproductive function. We therefore explored the effects of Pb and furan on male rat hypothalamic-pituitary-gonadal reproductive status, oxidative stress, inflammation, and genomic integrity. We found that co-exposure to Pb and furan reduced the activities of testicular function enzymes, endogenous antioxidant levels, total sulfhydryl group, and glutathione. Sperm abnormality, biomarkers of oxidative stress, inflammation, and p53 expression were increased in a dose-dependent manner by treatment with furan and Pb. Typical rat gonad histoarchitecture features were also damaged. Conclusively, co-exposure to Pb and furan induced male reproductive function derangement by decreasing the antioxidant defences in rats, increasing abnormalities in spermatozoa morphology, and reducing reproductive hormone in circulation. These pathophysiological alterations, if persistent, might provide a permissive environment for potentiating reproductive dysfunction and infertility.
An increasing number of studies demonstrated that alcohol vapor chamber is an effective way to model physical signs of alcohol use disorders. Although researchers are developing different vapor chambers to study chronic alcohol exposure model worldwide, few studies build and modify their own vapor chambers in China. Here, we designed and established an alcohol vapor chamber system for small animals. We described a paradigm showing how to control and monitor alcohol concentration in whole system. The vapor chamber system with several advantages including accommodating up to ten standard mouse cages. Furthermore, the system was tested by evaluating the blood alcohol concentration and neuron injury in mice. Importantly, the alcohol withdrawal after vapor exposure caused motor coordination impairment, anxiolytic- and depression-like behavior. Finally, the N-methyl-D-aspartate receptor (NMDAR)-mediated glutamatergic transmissions in the medial prefrontal cortex was changed after alcohol vapor exposure-induced behaviors. The frequency and amplitude of spontaneous excitatory postsynaptic currents between control and alcohol groups were not different, suggesting that alcohol exposure-induced behaviors are associated with the change in NMDAR response. Taken together, the new alcohol vapor chamber system was constructed, which would help to research the relationship between the stable alcohol exposure and withdrawal behaviors and to study chronic alcohol exposure-induced disorders in China.
Recently, cognitive impairments (CI) and behavioral abnormalities in patients with amyotrophic lateral sclerosis (ALS) have been reported. However, the underlying mechanisms have been poorly understood. In the current study, we explored the role of gut microbiota in CI of ALS patients. We collected fecal samples from 35 ALS patients and 35 healthy controls. The cognitive function of the ALS patients was evaluated using the Edinburgh Cognitive and Behavioral ALS Screen. We analyzed these samples by using 16S rRNA gene sequencing as well as both untargeted and targeted (bile acids) metabolite mapping between patients with CI and patients with normal cognition (CN). We found altered gut microbial communities and a lower ratio of Firmicutes/Bacteroidetes in the CI group, compared with the CN group. In addition, the untargeted metabolite mapping revealed that 26 and 17 metabolites significantly increased and decreased, respectively, in the CI group, compared with the CN group. These metabolites were mapped to the metabolic pathways associated with bile acids. We further found that cholic acid and chenodeoxycholic acid were significantly lower in the CI group than in the CN group. In conclusion, we found that the gut microbiota and its metabolome profile differed between ALS patients with and without CI and that the altered bile acid profile in fecal samples was significantly associated with CI in ALS patients. These results need to be replicated in larger studies in the future.
The current study aims to investigate a suitable adhesive for primary tooth enamel. Shear bond strength (SBS) of primary teeth and the length of resin protrusion were analyzed using one-way ANOVA with Bonferroni multiple comparison tests after etching with 35% H3PO4. SBS and marginal microleakage tests were conducted with Single Bond Universal (SBU)/Single Bond 2 (SB2) adhesives with or without pre-etching using a nonparametric Kruskal-Wallis test. Clinical investigations were performed to validate the adhesive for primary teeth restoration using Chi-square tests. Results showed that the SBS and length of resin protrusion increased significantly with the etching time. Teeth in the SBU with 35% H3PO4 pre-etching groups had higher bond strength and lower marginal microleakage than those in the SB2 groups. Mixed fractures were more common in the 35% H3PO4 etched 30 s + SB2/SBU groups. Clinical investigations showed significant differences between the two groups in cumulative retention rates at the 6-, 12- and 18-month follow-up evaluations, as well as in marginal adaptation, discoloration, and secondary caries at the 12- and 18-month follow-up assessments. Together, pre-etching primary teeth enamel for 30 s before SBU treatment improved clinical composite resin restoration, which can provide a suitable approach for restoration of primary teeth.
Case Report
Right heart thrombus (RHTh) with concurrent acute pulmonary embolism (PE) is rare and can seriously destabilize hemodynamics, leading to an emergency situation with high mortality. Diagnosis and treatment of RHTh with acute PE are not yet standardized. There are few reports of acute PE concurrent with RHTh and even less is known about patients with a right heart mural thrombus. For physicians, the diagnostic choice and treatment of these patients are particularly difficult due to the lack of knowledge. Here, we report a rare case of partial mural RHTh (type C RHTh) with acute PE. The mural mass in the right heart was initially diagnosed as atrial myxoma according to transthoracic echocardiography (TTE), and both pulmonary embolus and the mural mass were completely absorbed after administering Rivaroxiban. This case suggests that TTE alone is insufficient to identify and diagnoses a right heart mural mass such as this. However, novel oral anticoagulants may be effective at alleviating PE with type C RHTh.
Myocardin in biology and disease
Joseph M. Miano
2015, 29(1): 3-19.   doi: 10.7555/JBR. 29.20140151
+Abstract PDF 5076KB
Exosomes and their role in the micro-/macro-environment: a comprehensive review
Naureen Javeed, Debabrata Mukhopadhyay
2017, 31(5): 386-394.   doi: 10.7555/JBR.30.20150162
+Abstract PDF 185KB
Immune checkpoint inhibitors in cancer therapy
Eika S. Webb, Peng Liu, Renato Baleeiro, Nicholas R. Lemoine, Ming Yuan, Yaohe Wang
2018, 32(5): 317-326.   doi: 10.7555/JBR.31.20160168
+Abstract PDF 275KB
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
Platelets in hemostasis and thrombosis: Novel mechanisms of fibrinogen-independent platelet aggregation and fibronectinmediated protein wave of hemostasis
Yan Hou, Naadiya Carrim, Yiming Wang, Reid C. Gallant, Alexandra Marshall, Heyu Ni
2015, 29(6): 437-444.   doi: 10.7555/JBR.29.20150121
+Abstract PDF 610KB
Statistical analysis for genome-wide association study
Ping Zeng, Yang Zhao, Cheng Qian, Liwei Zhang, Ruyang Zhang, Jianwei Gou, Jin Liu, Liya Liu, Feng Chen
2015, 29(4): 285-297.   doi: 10.7555/JBR.29.20140007
+Abstract PDF 3937KB
Recent advances in targeting the autotaxin-lysophosphatidate-lipid phosphate phosphatase axis in vivo
Matthew G.K. Benesch, Xiaoyun Tang, Ganesh Venkatraman, Raie T. Bekele, David N. Brindley
2016, 30(4): 272-284.   doi: 10.7555/JBR.30.20150058
+Abstract PDF 462KB
Hepatic ischemia-reperfusion injury in liver transplant setting: mechanisms and protective strategies
Rampes Sanketh, Ma Daqing
2019, 33(4): 221-234.   doi: 10.7555/JBR.32.20180087
+Abstract + HTML PDF 1187KB
Autoantibodies in Alzheimer's disease: potential biomarkers, pathogenic roles, and therapeutic implications
Jianming Wu, Ling Li
2016, 30(5): 361-372.   doi: 10.7555/JBR.30.20150131
+Abstract PDF 426KB
Translating transitions - how to decipher peripheral human B cell development
Mats Bemark
2015, 29(4): 264-284.   doi: 10.7555/JBR.29.20150035
+Abstract PDF 858KB
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](983)
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](904)
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](1079)
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](970)
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](1262)
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 4KB](925)
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 4KB](1232)
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](1904)
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](891)
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 4KB](985)