• 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).
It is difficult for physicians to identify patients with metastatic nasopharyngeal carcinoma (NPC) who are sensitive to local treatment. Here, we aimed to establish a prognostic model for survival and to individualize treatments for patients with metastatic NPC. Data from 240 patients with metastatic NPC and received palliative chemotherapy with or without local treatmentand were collated from 2006 until 2020. Multivariable Cox regression was implemented to construct a nomogram which had a concordance index of 0.764 when predicting 1-, 3-, and 5-year overall survival (OS). We then classified patients according to risk, creating low- and high-risk groups using the nomogram. Differences in OS between the two groups was significant (P<0.001). In the low-risk group, the OS for patients who received local treatment was longer than those without (P=0.009). This novel nomogram is capable of accurately classifying patients according to risk and could also be used to determine who will respond best to local treatment.
Mast cell activation syndrome ( MCAS) includes a group of disorders which result in inappropriate release of inflammatory mediators from mast cells. These mediators can affect multiple organ systems and lead to significant morbidity, and possible fatality. Although reactions, typically in response to various nonspecific stimuli, are usually mild, they may put those with MCAS at increased risk of anaphylaxis. In this case report, we present two clinical scenarios of MCAS, and identify possible factors triggering mast cell mediator release. We also define a preoperative preventive pathway, outline anesthetic considerations, and discuss the management of immediate hypersensitivity reactions in patients with MCAS. Meticulous preoperative preparation, avoidance of triggers, and development of a plan to treat possible adverse organ responses are paramount of good outcomes.
Sterculia gum, the dry exudate of Sterculia versicolor and other members of the same genus, is used as a thickener and emulsifier in foods. It is generally considered safe as a food or drug, and its adverse reactions, such as Sterculia-induced liver injury, have never been reported. A 46-year-old woman was admitted to hospital with fatigue, nausea, abdominal distension, jaundice and a >16-fold increase in transaminase and bilirubin level. The patient had used Sterculia gum prior to the onset of her symptoms. Her symptoms and clinical indicators improved after treatment. The possibility of acute viral hepatitis, autoimmune hepatitis, and metabolic liver disease was excluded. After discharge from hospital, the patient had a severe liver injury again when re-exposed to Sterculia gum. And the Roussel Uclaf Causality Assessment Method score was updated from 5 to 7, which was consistent with probable drug-induced liver injury. This is the first report of Sterculia-induced liver injury. Clinicians need to be aware of the potential hepatotoxicity of Sterculia.
Tuberculosis (TB), is an infectious disease caused by Mycobacterium tuberculosis (M. tuberculosis), and presents with high morbidity and mortality. Alveolar macrophages play an important role in TB pathogenesis although there is heterogeneity and functional plasticity. This study aimed to show the characteristics of alveolar macrophages from bronchioalveolar lavage fluids (BALF) in active TB patients. Single-cell RNA sequencing (scRNA-seq) was performed on BALF cells from three patients with active TB and additional scRNA-seq data from three healthy adults were established as controls. Transcriptional profiles were analyzed and compared by differential geneexpression and functional enrichment analysis. We applied pseudo-temporal trajectory analysis to investigate correlations and heterogeneity within alveolar macrophage subclusters. Alveolar macrophages from active TB patients at the single-cell resolution are described. We found that TB patients have higher cellular percentages in five macrophage subclusters. Alveolar macrophage subclusters with increased percentages were involved in inflammatory signaling pathways as well as the basic macrophage functions. The TB-increased alveolar macrophage subsets might be derived from M1-like polarization state, before switching to an M2-like polarization state with the development of M. tuberculosis infection. Cell-cell communications of alveolar macrophages also increase and enhance in active TB patients. Overall, our study demonstrated the characteristics of alveolar macrophages from BALF in active TB patients by using scRNA-seq.
Orexin signaling has been associated with energy expenditure and brown adipose tissue (BAT) function. However, conflicting data exist in the field about how orexin signaling regulates BAT thermogenesis. In this study, we show that a specific orexin receptor type 2 (OX2R) agonist [Ala11, D-Leu15]-OxB (OB-Ala) inhibited intrascapular brown adipose tissue (iBAT) thermogenesis by reducing sympathetic output to iBAT. This effect is mediated by OX2Rs located on afferent nerve endings innervating iBAT instead of brown adipocyte itself. Microinjection of OB-Ala into iBAT inhibited iBAT thermogenesis in mice upon cold exposure and neuronal activity in the paraventricular nucleus (PVN). Findings suggest that OB-Ala could inhibit iBAT thermogenesis by attenuating sensory input thereby inhibiting the sympathetic-sensory iBAT feedback loop. Our study uncovers a novel primary action site of orexin in the regulation of energy balance.
High-affinity antibodies are widely used in diagnostics and for the treatment of human diseases. However, most antibodies are isolated from semi-synthetic libraries by phage display and do not possess in vivo affinity maturation, which is triggered by antigen immunization. It is therefore necessary to engineer the affinity of these antibodies by way of in vitro assaying. In this study, we optimized the affinity of two human monoclonal antibodies which were isolated by phage display in a previous related study. For the 42A1 antibody, which targets the liver cancer antigen glypican-3, the variant T57H in the second complementarity-determining region of the heavy chain (CDR-H2) exhibited a 2.6-fold improvement in affinity, as well as enhanced cell-binding activity. For the I4A3 antibody to severe acute respiratory syndrome coronavirus 2, beneficial single mutations in CDR-H2 and CDR-H3 were randomly combined to select the best synergistic mutations. Among these, the mutation S53P-S98T improved binding affinity (about 3.7 fold) and the neutralizing activity (about 12 fold) compared to the parent antibody. Taken together, single mutations of key residues in antibody CDRs were enough to increase binding affinity with improved antibody functions. The mutagenic combination of key residues in different CDRs creates additive enhancements. Therefore, this study provides a safe and effective in vitro strategy for optimizing antibody affinity.
Oligodendrocyte lineage cells (OL-lineage cells) are a cell population that are crucial for mammalian central nervous system (CNS) myelination. OL-lineage cells go through developmental stages, initially differentiating into oligodendrocyte precursor cells (OPCs), before becoming immature oligodendrocytes, then mature oligodendrocytes (OLs). While the main function of cell lineage is in myelin formation, and increasing number of studies have turned to explore the immunological characteristics of these cells. Initially, these studies focused on discovering how OPCs and OLs are affected by the immune system, and then, how these immunological changes influence the myelination process. However, recent studies have uncovered another feature of OL-lineage cells in our immune systems. It would appear that OL-lineage cells also express immunological factors such as cytokines and chemokines in response to immune activation, and the expression of these factors changes under various pathologic conditions. Evidence suggests that OL-lineage cells actually modulate immune functions. Indeed, OL-lineage cells appear to play both "victim" and "agent" in the CNS which raises a number of questions. Here, we summarize immunologic changes in OL-lineage cells and their effects, as well as consider OL-lineage cell changes which influences immune cells under pathological conditions. We also describe some of the underlying mechanisms of these changes and their effects. Finally, we describe several studies which use OL-lineage cells as immunotherapeutic targets for demyelination diseases.
The present study aims to investigate the therapeutic effect and mechanism of glycyrrhizin acid (GA) in rats with diabetic peripheral neuropathy (DPN) and high glucose-treated RSC96 cells. GA significantly mitigated nerve conduction velocity (NCV) deficit and morphological abnormality and reduced high-mobility group box-1 (HMGB1) expression in the sciatic nerves of diabetic rats independent of blood glucose and body weight. Notably, GA alleviated the increase of HMGB1 content and the decrease of cell viability in high glucose-stimulated RSC96 cells. Furthermore, GA obviously reduced the concentration of inflammatory cytokines in the sciatic nerves of diabetic rats and supernatants of high glucose-exposed RSC96 cells, then restored the decreased expression levels of neuritin-1 and nerve growth factor (NGF), and the increased expression levels of cleaved caspase-3 and neuron-specific enolase (NSE). Additionally, GA markedly inhibited receptor for advanced glycation end products (RAGE) protein expression, p38MAPK phosphorylation and the nuclear translocation of NF-κBp65 in diabetic rats and high glucose-exposed RSC96 cells. These findings were ascertained in RSC96 cells where the promotional effect of high glucose on inflammatory cytokines content, imbalance between caspase-3 activity and neurotrophic substance, RAGE protein expression, p38MAPK phosphorylation, and nuclear NF-κBp65 level were diminished following Hmgb1 siRNA treatment. Our findings indicate that GA may exert neuroprotection on DPN in diabetic rats by suppressing HMGB1, which led to extenuation of inflammation response, balance of NGF, neuritin-1 and caspase-3, as well as inactivation of RAGE/p38MAPK/NF-κBp65 signaling pathway. These data deepen our understanding of the pathogenesis of DPN and provide a theoretical basis for GA treatment of DPN.
The Journal of Biomedical Research--2022, 36(2)
Perspective
Review Article
Melanoma is a relentless type of skin cancer which involves myriad signaling pathways which regulate many cellular processes. This makes melanoma difficult to treat, especially when identified late. At present, therapeutics include chemotherapy, surgical resection, biochemotherapy, immunotherapy, photodynamic and targeted approaches. These interventions are usually administered as either a single-drug or in combination, based on tumor location, stage, and patients' overall health condition. However, treatment efficacy generally decreases as patients develop treatment resistance. Genetic profiling of melanocytes and the discovery of novel molecular factors involved in the pathogenesis of melanoma have helped to identify new therapeutic targets. In this literature review, we examine several newly approved therapies, and briefly describe several therapies being assessed for melanoma. The goal is to provide a comprehensive overview of recent developments and to consider future directions in the field of melanoma.
As a late endosomal/lysosomal transport protein of the P5-type, ATP13A2 is capable of removing the abnormal accumulation of α-synuclein, which maintains the homeostasis of metal ions and polyamines in the central nervous system. Furthermore, ATP13A2 regulates the normal function of several organelles such as lysosomes, endoplasmic reticulum (ER) and mitochondria, and maintains the normal physiological activity of neural cells. Especially, ATP13A2 protects dopaminergic (DA) neurons against environmental or genetically induced Parkinson's disease (PD). As we all know, PD is a neurodegenerative disease characterized by the loss of DA neurons in the substantia nigra pars compacta. An increasing number of studies have reported that the loss-of-function of ATP13A2 affects normal physiological processes of various organelles, leading to abnormalities and the death of DA neurons. Previous studies in our laboratory have also shown that ATP13A2 deletion intensifies the neuroinflammatory response induced by astrocytes, thus inducing DA neuronal injury. In addition to elucidating the normal structure and function of ATP13A2, this review summarized the pathological mechanisms of ATP13A2 mutations leading to PD in existing literature studies, deepening the understanding of ATP13A2 in the pathological process of PD and other related neurodegenerative diseases. This review provides inspiration for investigators to explore the essential regulatory role of ATP13A2 in PD in the future.
Original Article
Clopidogrel is a pro-drug which needs two-step metabolism to produce the active thiol metabolite. This study aimed to explore an efficient method to simultaneously determine the plasma clopidogrel, 2-oxo-clopidogrel (2-Oxo-CLP), and the clopidogrel active metabolite (CAM). A high-throughput liquid chromatography tandem mass spectrometry (LC-MS/MS) was therefore developed. The analytes were extracted from plasma by using methyl tert-butyl ether (MTBE). Chromatographic separation was performed on a C18 column under an isocratic elution, accompanied with acetonitrile and deionized water containing 0.1% formic acid. After optimizing the condition of LC-MS/MS, a stable linearity was observed in the standard curves over the concentration ranges of 0.05 to 50.0 ng/mL for clopidogrel, 0.5 to 50.0 ng/mL for 2-Oxo-CLP, and 0.5 to 100 ng/mL for clopidogrel active metabolite derivative (CAMD). The retention time was 4.78 minutes, 3.79 minutes, 3.59 minutes, and 4.82 minutes for clopidogrel, 2-Oxo-CLP, CAMD, and internal standard, respectively. Both the relative standard deviation and the relative error were within the requirement of operating criteria. No significant degradation of clopidogrel, 2-Oxo-CLP, and CAMD occurred under different storage conditions. This method was successfully validated in 3 patients with coronary artery disease. The results showed that the current LC-MS/MS method was efficient for simultaneously detecting clopidogrel, 2-Oxo-CLP, and CAM with fine linearity, accuracy, precision, and stability.
Aging and obesity contribute to muscle dysfunction. This study aimed to determine the cross-sectional associations between components of metabolic syndrome (MetS) and sarcopenia in 251 older community-dwelling Chinese. The total fat-free mass was measured by dual-energy X-ray absorptiometry, muscle strength (handgrip strength) by a handheld dynamometer, physical performance by 4-meter walk, 5-time chair stand test, and the short physical performance battery (SPPB). MetS was defined using the International Diabetes Federation (IDF) criteria. The participants with MetS had a higher appendicular skeletal muscle mass (ASM) and relative ASM (RASM). The males with MetS had higher handgrip strength, and the females with MetS had higher SPPB scores. After adjusting for age and body mass index, the participants with an increased waist circumference had a higher ASM, and those with increased diastolic blood pressure (DBP) also had higher handgrip strength. The males with elevated fasting blood glucose (FBG) levels had a lower gait speed. Components of MetS, such as DPB and FBG, were associated with muscle strength and physical performance in older adults. These results suggest that muscle strength and function should be considered in treating older adults with MetS.
This study aimed to investigate the effect and mechanism of valproic acid (VPA) on the neurosphere formation in rat embryonic cortical cells. We used free-floating neurosphere formation as a model system to evaluate the VPA on the proliferation of neural stem cells (NSCs). We found a time- and dose-dependent increase in neurosphere formation and NSC proliferation after VPA treatment. Further RNA-seq analysis demonstrated that the upregulated TGFβ1 signaling might attribute to the effect of VPA on the neurosphere formation and NSC proliferation. Consistently, the neurosphere formation and NSC proliferation were blocked by the treatment with SB431542, an inhibitor of TGFβ1 receptor. Moreover, in a coculture system, NSCs treated with VPA significantly reduced the oxygen-glucose deprivation-induced neuronal apoptosis. Taken together, our results showed that VPA could enhance neurosphere formation and NSC proliferation by activating TGFβ1, which might be a novel therapeutic strategy for neurological disorders.
Case Report
Takayasu arteritis (TA) is a chronic, nonspecific inflammatory disease of large and medium-sized vessels that primarily involves the aorta and its branches. TA involving the pulmonary arteries has a prevalence ranging from 14% to 86%, which can lead to pulmonary hypertension, a progressive increase in pulmonary artery pressure, and eventually death from right heart failure. The presentation of pulmonary arteritis (PA) is very nonspecific, with a reported misdiagnosis rate of up to 60% and a diagnosis time ranging from 1 month to more than 10 years. The clinical manifestation of pleural effusion is very rare in both TA and PA cases. Based on our literature review, this is the 6th reported case of TA with pleural effusion, and the specific mechanism of TA with pleural effusion is still unclear. The characteristics of this case and the previously reported cases are summarized in this article to improve the understanding of TA and PA and reduce the misdiagnosis rate.
Letter to the Editor
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
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
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
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
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
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
Deciphering the role of hedgehog signaling in pancreatic cancer
Dongsheng Gu, Kelly E Schlotman, Jingwu Xie
2016, 30(5): 353-360.   doi: 10.7555/JBR.30.20150107
+Abstract PDF 376KB
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](908)
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](796)
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](943)
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](888)
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](1025)
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](845)
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](1049)
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](1534)
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](854)
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](815)