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).
Glial cells play an essential part of neuron system. They can not only serve as structural blocks in human brain, but also participate in many biological processes. Extensive studies have shown that astrocytes and microglia play an important role in neurodegenerative disease, such as Alzheimer's disease, Parkinson's disease, and Huntington disease, as well as glioma, epilepsy, ischemic stroke and infections. Positron emission tomography is a functional imaging technique providing molecular-level information before anatomic changes are visible and have been widely used in many above-mentioned diseases. In this review, we focus on the positron emission tomography tracers used in pathologies related to glial cells, such as glioma, Alzheimer's disease, and neuroinflammation.
Amyotrophic lateral sclerosis (ALS) is known as a progressive paralysis disorder characterized by degeneration of upper and lower motor neurons and has an average survival time of three to five years. Growing evidences have suggested the bidirectional link between gut microbiota and neurodegeneration. Here we aimed to report one female case with ALS who benefited from washed microbiota transplantation (WMT), an improved fecal microbiota transplantation (FMT), through transendoscopic enteral tube during 12-month follow-up. Notedly, the accidental scalp trauma the patient suffered later was treated with prescribed antibiotics which caused ALS deterioration. The subsequent rescue WMTs successfully stopped the progression of the disease with quick improvement. The plateaus and reversals occurred during the whole course of WMT. The stool and blood samples from the first WMT to the last were collected for dynamic microbial and metabolomic analysis. We observed the microbial and metabolomic changing trend consistent with the disease status. This case report for the first time shows the direct clinical evidence on using WMT for treating ALS, indicating that WMT may be the novel treatment strategy for controlling this so-called incurable disease.
It is difficult for physicians to identify patients with metastatic nasopharyngeal carcinoma (NPC) who are sensitive to local treatment of metastases. Here, we aimed to establish a prognostic model for survival and individualize treatments for patients with metastatic NPC. Data were collated from 240 NPC patients diagnosed with metachronous metastasis between 2006 and 2020 who received palliative chemotherapy with or without local treatment. 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 were 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 shows good performance in classifying patients according to risk and may also be a promising tool for determining who responds best to local treatment. Further validation using external center data is warranted.
In this paper, we propose a framework based deep learning for medical image translation using paired and unpaired training data. Initially, a deep neural network with an encoder-decoder structure is proposed for image-to-image translation using paired training data. A multi-scale context aggregation approach is then used to extract various features from different levels of encoding, which are used during the corresponding network decoding stage. At this point, we further propose an edge-guided generative adversarial network for image-to-image translation based on unpaired training data. An edge constraint loss function is used to improve network performance in tissue boundaries. To analyze framework performance, we conducted five different medical image translation tasks. The assessment demonstrates that the proposed deep learning framework significant improvement beyond state-of-the-arts.
Mounting evidence indicate that long non-coding RNAs (lncRNAs) have critical roles in colorectal cancer (CRC) progression, providing many potential diagnostic biomarkers, prognostic biomarkers, and treatment targets. Here, we sought to investigate the role and underlying regulatory mechanism of lncRNA small nucleolar RNA host gene 16 (SNHG16) in CRC. The expressions of SNHG16 in CRC were identified by RNA-sequencing and quantitative reverse transcription PCR. The functions of SNHG16 were explored by a series of in vitro and in vivo assays (colony formation assay, flow cytometry assay, and xenograft model). Bioinformatics analysis, RNA fluorescence in situ hybridization and luciferase reporter assay were used to investigate the regulatory mechanism of effects of SNHG16. SNHG16 was found to be significantly elevated in human CRC tissues and cell lines. Functional studies suggested that SNHG16 promoted CRC cells growth both in vitro and in vivo. Mechanistically, we identified that SNHG16 expressed predominantly in the cytoplasm. SNHG16 could interact with miR-214-3p and up-regulated its target ABCB1. This study indicated that SNHG16 plays an oncogenic role in CRC, suggesting it could be a novel biomarker and therapeutic target in CRC.
Spinal cord injury (SCI) leads to permanent deficits in neural function without effective therapies, which places a substantial burden on families and society. Astrocytes, the major glia supporting the normal function of neurons in the spinal cord, become active and form glial scars after SCI, which has long been regarded as a barrier for axon regeneration. However, recent progress has indicated the beneficial role of astrocytes in spinal repair. During the past three decades, astrocyte transplantation for SCI treatment has gained increasing attention. In this review, we first summarize the progress of using rodent astrocytes as the primary step for spinal repair. Rodent astrocytes can survive well, migrate extensively, and mature in spinal injury; they can also inhibit host reactive glial scar formation, stimulate host axon regeneration, and promote motor, sensory, respiratory, and autonomic functional recovery. Then, we review the progress in spinal repair by using human astrocytes of various origins, including fetal brain, fetal spinal cord and pluripotent stem cells. Finally, we introduce some key questions that merit further research in the future, including rapid generation of large amounts of human astrocytes with high purity, identification of the right origins of astrocytes to maximize neural function improvement while minimizing side effects, testing human astrocyte transplantation in chronic SCI, and verification of the long-term efficacy and safety in large animal models.
Mast cell activation syndrome (MCAS) includes a group of disorders that result in the 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.
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 influence 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 Journal of Biomedical Research--2022, 36(3)
J Biomed Res 2022, 36(3): 147-154.
doi: 10.7555/JBR.36.20220040
Even though randomized controlled clinical trials (RCTs) have been accepted as the gold standard for official assessment of novel interventions, there is a substantial gap between the efficacy observed in RCTs and the impact on clinical practice and in terms of patient benefit. While real-world studies (RWS) are emerging to confer valuable complementing evidence in this regard and beyond, the evolving role of RWS is yet to be agreed. This article delineates an updated profile of RWS covering effectiveness verification, rare adverse effects discovery, indication repurposing, to name a few. RWS tends not only to improve the efficiency of clinical investigations for regulatory approval, but also optimizes the whole-life cycle evaluation of biomedical/pharmaceutical products.
J Biomed Res 2022, 36(3): 155-166.
doi: 10.7555/JBR.36.20220003
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.
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 fluid (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 subclusters 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 increased and enhanced in active TB patients. Overall, our study demonstrated the characteristics of alveolar macrophages from BALF in active TB patients by using scRNA-seq.
The present study aims to investigate the therapeutic effect and mechanism of glycyrrhizic acid (GA) in diabetic peripheral neuropathy (DPN). 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 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 nerve growth factor (NGF) and neuritin-1, and the increased expression levels of cleaved caspase-3 and neuron-specific enolase. Additionally, GA markedly inhibited receptor for advanced glycation end products (RAGE) expression, p38MAPK phosphorylation, and the nuclear translocation of NF-κBp65 in diabetic rats and high glucose-exposed RSC96 cells. The promotional effect of high glucose in RSC96 cells was diminished following Hmgb1 siRNA treatment. Our findings indicate that GA may exert neuroprotection on DPN by suppressing HMGB1, which lead to extenuation of inflammation response, balance of NGF, neuritin-1 and caspase-3, as well as inactivation of RAGE/p38MAPK/NF-κBp65 signaling pathway.
J Biomed Res 2022, 36(3): 195-207.
doi: 10.7555/JBR.36.20220033
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. 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.
Osteoporotic vertebral compression fracture (OVCF) has become a major public health issue that becomes more pressing with increasing global aging. Percutaneous kyphoplasty (PKP) is an effective treatment for OVCF. Robot-assisted PKP has been utilized in recent years to improve accuracy and reduce complications. However, the effectiveness of robot-assisted PKP in the treatment of multi-segmental OVCF has yet to be proved. This study was designed to compare the efficacy of robot-assisted and conventional fluoroscopy-assisted multi-segmental PKP. A total of 30 cases with multi-segmental OVCF between April 2019 and April 2021 were included in this study. Fifteen cases were assigned to the robot-assisted PKP group (robot group) and 15 cases to the conventional fluoroscopy-assisted PKP group (conventional fluoroscopy group). The number of fluoroscopic exposures, fluoroscopic dose, operation time, cement leakage rate, visual analog scale (VAS) score, vertebral kyphosis angle (VKA), and height of fractured vertebral body (HFV) were compared between the 2 groups. The number of fluoroscopic exposures, fluoroscopic doses, and cement leakage rates in the robot group were lower than in the conventional fluoroscopy group (P<0.05) while the operative time in the robot group was longer than in the conventional fluoroscopy group (P<0.05). VAS score and VKA were decreased and HFV was increased after surgery in both groups (P<0.05). Therefore, robot-assisted PKP for the treatment of multi-segmental OVCF can reduce the number of fluoroscopic exposures, fluoroscopic doses, and cement leakage compared to conventional treatment. As such, robot-assisted PKP has good application prospects and is potentially more effective in the treatment of multi-segmental OVCF.
J Biomed Res 2022, 36(3): 215-220.
doi: 10.7555/JBR.36.20220044
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.
2015, 29(1): 3-19.
doi: 10.7555/JBR. 29.20140151
2017, 31(5): 386-394.
doi: 10.7555/JBR.30.20150162
2018, 32(5): 317-326.
doi: 10.7555/JBR.31.20160168
2015, 29(4): 285-297.
doi: 10.7555/JBR.29.20140007
2016, 30(5): 353-360.
doi: 10.7555/JBR.30.20150107
2015, 29(4): 264-284.
doi: 10.7555/JBR.29.20150035
2014, 28(2): 81-97.
doi: 10.7555/JBR.27.20120136
2014, 28(5): 388-395.
doi: 10.7555/JBR.28.20140015
2013, 27(1): 1-13.
doi: 10.7555/JBR.27.20120077
2011, 25(4): 266-273.
doi: 10.1016/S1674-8301(11)60036-5
2013, 27(2): 85-102.
doi: 10.7555/JBR.27.20120064
2011, 25(6): 418-424.
doi: 10.1016/S1674-8301(11)60055-9
Authors and Reviewers
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