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).
Liver diseases with the central pathogenetic mechanism of oxidative stress is one of the main causes of mortality worldwide. Therefore, dihydroquinoline derivatives, which are precursors of hepatoprotectors and have antioxidant activity, are of interest. We have previously found that some compounds in this class have the ability to normalize redox homeostasis under experimental conditions. Here, we initially analyzed the hepatoprotective potential of the dihydroquinoline derivative 1-benzoyl-6-hydroxy-2,2,4-trimethyl-1,2-dihydroquinoline (BHDQ) for carbon tetrachloride (CCl4)-induced liver injury in rats. Result suggested that BHDQ normalized the alanine aminotransferase, aspartate aminotransferase, and gamma-glutamyl transpeptidase in serum. We also observed an improvement in liver tissue morphology related to BHDQ. Animals with CCl4-induced liver injuries treated with BHDQ had less oxidative stress compared to animals with (CCl4)-induced liver injury. BHDQ promoted activation changes in superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, and glutathione transferase on control values in animals with (CCl4)-induced liver injury. BHDQ also activated gene transcription in Sod1 and Gpx1 via nuclear factor erythroid 2-related factor 2 and Forkhead box other 1 factors. Therefore, the compound of concern has a hepatoprotective effect by inhibiting the development of necrotic processes in the liver tissue, through antioxidation.
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 is 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.
Sirtuin 3 (SIRT3), a main family member of mitochondrial deacetylase, targets 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 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 co-activator-1alpha (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.
Alzheimer's disease (AD) is an age-related neurodegenerative disease characterized by progressive cognitive defects. The role of the central immune dominated by microglia in the progression of AD has been extensively investigated. However, little is known about the peripheral immune system in AD pathogenesis. Recently, with the discovery of the meningeal lymphatic vessels and glymphatic system, the roles of acquired immunity in the maintenance of central homeostasis and neurodegenerative diseases have attracted increasing attention. T cells not only regulate the function of neurons, astrocytes, microglia, oligodendrocytes and brain microvascular endothelial cells, but also participate in clearance of β-amyloid (Aβ) plaques. Apart from producing antibodies to bind Aβ peptides, B cells affect Aβ-related cascades via a variety of antibody-independent mechanisms. This review systemically summarizes the recent progress in understanding pathophysiological roles of T cells and B cells in AD.
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 brings significant improvement beyond state-of-the-arts.
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 evidence has 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 a transendoscopic enteral tube during a 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.
The superior vena cava (SVC) is the main component of non-pulmonary vein (PV) ectopy in patients with atrial fibrillation (AF). Researchers have found that epicardial adipose tissue (EAT) volume is related to the AF substrate, which can be defined by the low voltage area (LVA). This study aimed to investigate the relationship between SVC-EAT and SVC-AF. Twenty-six patients with SVC-AF triggers were identified as SVC-AF group. Other three groups were defined and included as LVA-AF group (LVA>5%), non-LVA-AF group (LVA<5%) and physical examination (PE) group. EAT around left atrium (LA-EAT) and SVC-EAT volumes were obtained using a cardiac risk assessment module. According to the SVC/LA-EAT ratio, there are significant differences between SVC-AF group and three control groups (SVC-AF group 0.092±0.041 vs. LVA-AF group 0.054±0.026, non-LVA-AF group 0.052±0.022, and PE group 0.052±0.019, P<0.001). Receiver operating characteristic curve analysis suggests the optimal cut-off point is 6.8% for detecting SVC-AF patients, with 81.1% sensitivity, 73.1% specificity, and an area under the curve of 0.83 (95% confidence interval, 0.75–0.91). Those with SVC-AF have a higher SVC/LA-EAT ratio and empirical SVC isolation could be considered if the SVC/LA-EAT ratio was over 6.8%.
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.
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(4)
J Biomed Res 2022, 36(4): 221-230.
doi: 10.7555/JBR.36.20220060
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.
J Biomed Res 2022, 36(4): 231-241.
doi: 10.7555/JBR.36.20220049
Mounting evidence indicates 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 cell growth both in vitro and in vivo. Mechanistically, we identified that SNHG16 is 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.
Genetic variants within or near the transcription factor 4 gene (TCF4) are robustly implicated in psychiatric disorders including schizophrenia. However, the biological pleiotropy poses considerable obstacles to dissect the potential relationship between TCF4 and those highly heterogeneous diseases. Through integrative transcriptomic analysis, we demonstrated that TCF4 is preferentially expressed in cortical interneurons during early brain development. Therefore, disruptions of interneuron development might be the underlying contribution of TCF4 perturbation to a range of neurodevelopmental disorders. Here, we performed chromatin immunoprecipitation sequencing (ChIP-seq) of TCF4 on human medial ganglionic eminence-like organoids (hMGEOs) to identify genome-wide TCF4 binding sites, followed by integration of multi-omics data from human fetal brain. We observed preferential expression of the isoform TCF4-B over TCF4-A. De novo motif analysis found that the identified 5916 TCF4 binding sites are significantly enriched for the E-box sequence. The predicted TCF4 targets in general have positively correlated expression levels with TCF4 in the cortical interneurons, and are primarily involved in biological processes related to neurogenesis. Interestingly, we found that TCF4 interacts with non-bHLH proteins such as FOS/JUN, which may underlie the functional specificity of TCF4 in hMGEOs. This study highlights the regulatory role of TCF4 in interneuron development and provides compelling evidence to support the biological rationale linking TCF4 to the developing cortical interneuron and psychiatric disorders.
J Biomed Res 2022, 36(4): 255-268.
doi: 10.7555/JBR.36.20220072
Amyloids have traditionally been considered pathologic protein aggregates which contribute to neurodegeneration. New evidence however increasingly suggests that non-pathological amyloids are formed in animals during normal development. Amyloid-like aggregate formation was originally thought to be a conserved feature of animal gametogenesis. This hypothesis was based on findings which suggest that regulated amyloid formations govern yeast meiosis by way of meiosis-specific RNA binding proteins. Additional support came from studies which demonstrate that DAZL, a mammalian gametogenesis-specific RNA binding protein, also forms SDS-resistant aggregates in vivo. Here, we report evidence of aggregated BOULE formations, another DAZ family protein, during sperm development. Data suggest that in mouse testis, BOULE forms SDS-resistant amyloid-like aggregates. BOULE aggregate formation correlates with dynamic developmental expression during spermatogenesis but disappeared in Boule knockout testis. We also mapped essential small region in vitro BOULE aggregations, immediately downstream DAZ repeats, and found that aggregations positively correlated with temperature. We also performed enhanced UV cross-linking immunoprecipitation on BOULE aggregates from mouse testes and found that aggregates bind with a large number of spermatogenesis-related mRNAs. These findings provide insight into the amyloidogenic properties of gametogenesis-specific RNA binding proteins as a conserved feature in mammalian reproduction. Further investigation is warranted to understand the functional significance of BOULE amyloid-like formation during mouse spermatogenesis.
J Biomed Res 2022, 36(4): 269-278.
doi: 10.7555/JBR.36.20220086
Microtubule-severing proteins (MTSPs), are a family of proteins which use adenosine triphosphate to sever microtubules. MTSPs have been shown to play an important role in multiple microtubule-involved cellular processes. One member of this family, fidgetin (FIGN), has also been shown to have an important role in male fertility; however, no studies have explored fidgetin's roles in female fertility. In this study, we found mouse fidgetin is rich within oocyte zona pellucida (ZP) and is the only MTSP member to do so. Fidgetin also appears to interact with all three ZP proteins. These findings prompted us to propose that fidgetin might prevent polyspermy. Results from in vitro maturation oocytes analysis showed that fidgetin knockdown did cause polyspermy. We then deleted all three fidgetin isoforms with CRISPR/Cas9 technologies; however, female mice remained healthy and with normal fertility. Of all mouse MTSPs, only the mRNA level of fidgetin-like 1 (FIGNL1) significantly increased. Therefore, we assert that fidgetin-like 1 compensates FIGN's roles in Fign-knockout female mice.
J Biomed Res 2022, 36(4): 279-294.
doi: 10.7555/JBR.36.20220059
Intrauterine adhesion (IUA) is a common clinical endometrial disease, which can severely damage the fertility and quality of life in women. This study aims to find the differentially expressed endogenous peptides and their possible roles in IUA. Liquid chromatography-mass spectrometry was used to identify the peptidomic profiling of IUA tissues, and the differentially expressed peptides were screened out. Using real-time quantitative PCR, Western blotting, and immunocytochemistry staining, the function of six endogenous peptides was verified in vitro. It was found that peptide 6 (T6) (peptide sequence: TFGGAPGFPLGSPLSSVFPR) could inhibit the expression of TGF-β1-induced cell fibrosis in human endometrial stromal cell line and primary human endometrial stromal cell at a concentration of 50 μmol/L. This study provides new targets for further clarifying the formation and prevention of IUA.
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
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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