The Ebola virus (EBOV), a member of the Filoviridae family, is a highly pathogenic agent responsible for severe hemorrhagic fever in humans. Understanding the molecular mechanisms governing its replication is critical for developing effective antiviral strategies. VP35-TurboID immunosuppression coupled with quantitative mass spectrometry identified Septin9, the host GTP-binding protein which played a role in cytoskeletal regulation, as a novel interactor of VP35. Western blotting and Far-Western blotting confirmed the direct interaction and demonstrated that the C-terminal region of VP35 was the critical binding domain. Functionally, EBOV replication as well as the formation of viral inclusion bodies (VIBs) was demonstrated to be significantly suppressed by Septin9 knockdown and depletion, as shown by the EBOV minigenome (EBOV MG) and the transcription- and replication-competent virus-like particles (trVLPs) system. This study reveals that VP35 engages in a specific interaction with the GTP-binding protein Septin9, thereby impeding EBOV replication through the disruption of inclusion bodies. The overarching objective of this study is to significantly enhance our understanding about the pathogenic mechanism of EBOV and offer a robust theoretical foundation and solid empirical support for the formulation of innovative therapeutic strategies against EBOV.
Virus Replication/physiology* ; Septins/physiology* ; Humans ; Ebolavirus/physiology* ; Inclusion Bodies, Viral/metabolism* ; Viral Regulatory and Accessory Proteins/metabolism* ; Hemorrhagic Fever, Ebola/virology*

Metaiodobenzylguanidine (MIBG) is an analog of norepinephrine that accumulates in sympathetic nerve endings soon after intravenous administration. The degree of accumulation reflects the uptake, storage and release of transmitters by noradrenergic neurons. Myocardial imaging with ¹²³I labeled MIBG ( ¹²³I-MIBG) can be used to estimate the extent of local myocardial sympathetic nerve damage, which has been widely used in the diagnosis and treatment of various heart diseases. In recent years, numerous studies have been carried out on the application of ¹²³I-MIBG in the diagnosis of degenerative diseases of the nervous system (such as Parkinson's disease and dementia of Lewy body), and have made some achievements. The purpose of this review is to summarize the current clinical application of ¹²³I-MIBG myocardial imaging in the diagnosis of dementia with Lewy bodies, the problems in imaging technology and the possible research directions in the future, so as to provide valuable reference information for clinicians to reasonably and accurately apply this technology in the early diagnosis and discrimination of dementia.
Humans ; Lewy Bodies ; 3-Iodobenzylguanidine ; Lewy Body Disease/diagnostic imaging* ; Iodine Radioisotopes

Nuclear bodies are membrane-free nuclear substructures that are localized in the mammalian nuclear matrix region. They are multiprotein complexes that recruit other proteins to participate in various cellular activities, such as transcription, RNA splicing, epigenetic regulation, tumorigenesis and antiviral defense. It is of great significance to clarify the functions and regulatory mechanisms of nuclear bodies to probe related diseases and virus-host interactions. This review takes several nuclear bodies associated proteins as examples, summarizes the formation process, structure and functions of nuclear bodies, and focuses on their important roles in antiviral infection. It is expected to provide new insight into host antiviral mechanisms.
Animals ; Cell Nucleus ; Epigenesis, Genetic ; Intranuclear Inclusion Bodies/metabolism* ; Nuclear Proteins/metabolism*

Alzheimer Disease ; China ; Consensus ; Humans ; Lewy Bodies ; Lewy Body Disease/drug therapy*

Dementia with Lewy bodies(DLB) is the second most common neurodegenerative disease. However, DLB might not be adequately diagnosed due to its variety of clinical symptoms. The authors present 65-year-old Mrs. A. who showed Parkinson's movement, cognitive decline, psychological symptoms, and autonomic dysfunction. According to the clinical features and biological markers in the recently revised DLB criteria, Mrs. A. was diagnosed with probable DLB. Differential diagnoses of delirium, Parkinson's dementia, and Alzheimer's dementia were discussed. Psychopharmacological treatments of antidepressants or anxiolytics caused intolerable side effects and showed little efficacy to Mrs. A. She experienced two episodes of hyponatremia during her one-year treatment. Recovery from neurological symptoms due to the first hyponatremia was time-consuming, and in the second, it was associated with changes in the level of consciousness despite relatively mild hyponatremia. A fall that occurred in the latter part of treatment triggered remarkable deterioration of DLB symptoms and daily life function. Prevention of falls is important for maintaining the quality of life of patients with DLB.
Accidental Falls ; Aged ; alpha-Synuclein ; Anti-Anxiety Agents ; Antidepressive Agents ; Biomarkers ; Consciousness ; Delirium ; Dementia ; Diagnosis ; Diagnosis, Differential ; Humans ; Hyponatremia ; Lewy Bodies ; Neurodegenerative Diseases ; Quality of Life

Primary age-related tauopathy (PART) is characterized by tau neurofibrillary tangles (NFTs) in the absence of amyloid plaque pathology. In the present study, we analyzed the distribution patterns of phosphorylated 43-kDa TAR DNA-binding protein (pTDP-43) in the brains of patients with PART. Immunohistochemistry and immunofluorescence double-labeling in multiple brain regions was performed on brain tissues from PART, Alzheimer's disease (AD), and aging control cases. We examined the regional distribution patterns of pTDP-43 intraneuronal inclusions in PART with Braak NFT stages > 0 and ≤ IV, and a Thal phase of 0 (no beta-amyloid present). We found four stages which indicated potentially sequential dissemination of pTDP-43 in PART. Stage I was characterized by the presence of pTDP-43 lesions in the amygdala, stage II by such lesions in the hippocampus, stage III by spread of pTDP-43 to the neocortex, and stage IV by pTDP-43 lesions in the putamen, pallidum, and insular cortex. In general, the distribution pattern of pTDP-43 pathology in PART cases was similar to the early TDP-43 stages reported in AD, but tended to be more restricted to the limbic system. However, there were some differences in the distribution patterns of pTDP-43 between PART and AD, especially in the dentate gyrus of the hippocampus. Positive correlations were found in PART between the Braak NFT stage and the pTDP-43 stage and density.
Aged ; Aged, 80 and over ; Aging ; metabolism ; pathology ; Brain ; metabolism ; pathology ; DNA-Binding Proteins ; metabolism ; Disease Progression ; Female ; Humans ; Immunohistochemistry ; Inclusion Bodies ; pathology ; Male ; Middle Aged ; Neurofibrillary Tangles ; metabolism ; pathology ; Neurons ; metabolism ; pathology ; Severity of Illness Index ; Tauopathies ; metabolism ; pathology

Abstract　　The promyelocytic leukemia (PML) gene encoded PML protein as a tumor suppressor protein, plays important roles in the occurrence and development of various cancers including acute promyelocytic leukemia. Recent studies have indicated that there are a variety of post-translational modifications of the PML protein, such as SUMOylation, ubiquitination, phosphorylation, and acetylation in cells. These modifications of the PML protein can directly affect the formation of PML nuclear bodies (PML-NBs), repair DNA damage, and modulate cell apoptosis. Furthermore, the abnormal modifications of PML not only result in the occurrence of hematopoietic tumors, but also are closely related to the drug-resistance of cancer. Therefore, investigating the post-translational modifications of PML is significant to uncover the mechanism of formation and functions of PML-NBs, thus contributing to the prevention and treatment of related hematopoietic tumors. In this review, the characteristics of the post-translational modifications of PML protein and the relationship between these modifications and functions of PML-NBs are summarized so as to provide the potential targets for the treatment of related cancers.
Humans ; Intranuclear Inclusion Bodies ; Leukemia, Promyelocytic, Acute ; Nuclear Proteins ; Promyelocytic Leukemia Protein ; Protein Processing, Post-Translational

INTRODUCTION: Haemoglobinopathy testing is performed for carrier screening and evaluation of microcytic anaemia. We evaluated the effectiveness of thalassaemia screening tests at our institution and suggest ways of improving the testing algorithm. MATERIALS AND METHODS: A total of 10,084 non-antenatal and 11,364 antenatal samples with alkaline gel electrophoresis (AGE), capillary electrophoresis (CE), haemoglobin H (HbH) inclusion test, mean corpuscular haemoglobin (MCH) and mean corpuscular volume (MCV) were retrospectively reviewed. A subgroup of 187 samples with genetic testing was correlated with HbH inclusions and MCH/ MCV. The effect of iron deficiency on percentage hemoglobin A2 (HbA2) was studied. RESULTS: HbH inclusion test showed low sensitivity of 21.43% for α-thalassaemia mutations but higher sensitivity of 78.95% for deletion. By receiver operating characteristic (ROC) analysis, MCH ≤28 pg or MCV ≤80 fl for non-antenatal samples and MCH ≤27 pg or MCV ≤81 fl for antenatal samples had >98% sensitivity for HbH inclusions. Above these thresholds, the probability that HbH inclusions would be absent was <99% (negative predictive value [NPV] >99%). MCH ≥28 pg had 100% sensitivity (95% CI 95.63%-100%) for α-thalassaemia mutations and 97.68% calculated NPV in the antenatal population. Detection of haemoglobin variants by CE correlated highly with AGE (99.89% sensitivity, 100% specificity). Severe iron deficiency reduced HbA2 in hemoglobin ( <0.001) and α-thalassaemia ( = 0.0035), but not in β-thalassaemia. CONCLUSION MCH/MCV thresholds have adequate sensitivity for α-thalassaemia in the antenatal population, and genotyping plays an important role as HbH inclusion test shows low sensitivity. CE without AGE, may be used as initial screening for haemoglobin variants. Our study provides contemporary data to guide thalassaemia screening algorithms in Singapore.
Blood Protein Electrophoresis ; Electrophoresis, Capillary ; Erythrocyte Inclusions ; pathology ; Erythrocyte Indices ; Female ; Genetic Testing ; Hemoglobin H ; analysis ; Humans ; Male ; Mass Screening ; Pregnancy ; Pregnancy Complications, Hematologic ; blood ; diagnosis ; Retrospective Studies ; Sensitivity and Specificity ; Singapore ; alpha-Thalassemia ; blood ; diagnosis

MYH9-related disorders (MYH9RD) are autosomal-dominant disorders characterized by macrothrombocytopenia with or without leukocyte inclusion bodies or extra-hematological features, such as sensorineural deafness and renal impairment. MYH9RD can be misdiagnosed as an acquired form of thrombocytopenia including immune thrombocytopenic purpura (ITP). This leads to delayed diagnosis or administration of ineffective treatment. In the present study, we investigated the clinical and molecular characteristics of five unrelated Korean patients with MYH9RD and their family members, from four institutions. We reviewed clinical and laboratory data including extra-hematological manifestations. MYH9 pathogenic variants were detected by direct sequencing in all probands and the affected family members (N=10): two probands with c.5521G>A (p.Glu1841Lys) and one proband each with c.99G>T (p.Trp33Cys), c.287C>T (p.Ser96Leu), and c.3493C>T (p.Arg1165Cys). All patients had macrothrombocytopenia. Only the proband with Ser96Leu had extra-hematological manifestations. Past history revealed that two patients had been misdiagnosed with ITP and one of them had received a splenectomy. We validated the frequency of misdiagnosis (~20%) and genotype-phenotype correlations through a comprehensive review of previously reported cases of MYH9RD in Korea. It is important to suspect MYH9RD in patients with thrombocytopenia, and timely identification of macrothrombocytopenia and MYH9 pathogenic variants is required for early and accurate diagnosis of MYH9RD.
Deafness ; Delayed Diagnosis ; Diagnosis ; Diagnostic Errors ; Genetic Association Studies ; Humans ; Inclusion Bodies ; Korea ; Leukocytes ; Purpura, Thrombocytopenic, Idiopathic ; Splenectomy ; Thrombocytopenia

OBJECTIVES: Parkinson disease (PD) is frequently associated with olfactory disorder at early stage, which is caused by deposition of Lewy bodies emerging from the olfactory bulb to higher olfactory centers. Early detection of olfactory disorder in the patients with PD may lead to the early diagnosis and treatment for this refractory disease. METHODS: Visual analog scale (VAS), Jet Stream Olfactometry, and Japanese smell identification test, Open Essence (OE), were carried out on 39 patients with PD. Thirty-one patients with postviral olfactory disorder (PVOD), which was caused by the olfactory mucosal dysfunction, were also enrolled in this study as control. RESULTS: There were no significant differences in detection thresholds (2.2 vs. 1.4, P=0.13), recognition thresholds (3.9 vs. 3.5, P=0.39) and OE (4.8 vs. 4.2, P=0.47) between PVOD and PD, while VAS scores of PVOD and PD were significantly different (2.0 and 6.2, P<0.01). In OE, significant differences were observed in the accuracy rates of menthol (68% vs. 44%, P=0.04) and Indian ink (42% vs. 15%, P=0.01) between PVOD and PD. Of particular interest, patients with PVOD tended to select “no detectable,” while patients with PD tended to select wrong alternative other than “no smell detected.” CONCLUSION: Discrepancy between VAS and OE, and high selected rates of wrong alternative other than “undetectable” in OE might be significant signs of olfactory dysfunction associated with PD.
Asian Continental Ancestry Group ; Early Diagnosis ; Humans ; Ink ; Lewy Bodies ; Menthol ; Olfactometry ; Olfactory Bulb ; Parkinson Disease ; Rivers ; Smell ; Visual Analog Scale