Integrative molecular medicine最新文献

{"title":"Two genetic disorders (TRMU and SCYL1) explaining transient infantile liver failure in one patient","authors":"T. Campos, E. Teles, E. Rodrigues, C. Nogueira, L. Vilarinho, M. Leão","doi":"10.15761/IMM.1000399","DOIUrl":"https://doi.org/10.15761/IMM.1000399","url":null,"abstract":"Introduction: Paediatric acute liver failure (PALF) has an extremely heterogeneous aetiology, with some genetic disorders being associated with recurrent/transient episodes of infantile hepatopathy. Here, we report a patient who experienced a severe episode of liver failure with complete recovery, and in whom were discovered two genetic disorders possibly explaining this occurrence: a mitochondrial disease caused by pathogenic variants in TRMU gene and the CALFAN syndrome secondary to mutations in SCYL1 gene. Case presentation: Healthy female child who was admitted at hospital by the age of 13 months due to acute hepatic failure in context of febrile flu. Hepatotropic infectious diseases were excluded and metabolic evaluation was normal, with exception of positive allopurinol testing. Liver biopsies revealed focal ballooning of hepatocytes and pronounced fibrosis. The liver function gradually recovered. From age of 3 years, she developed intention tremor, and after the age of 10 progressive ataxia and motor-sensory neuropathy. She is now 25 years-old and presents a cerebellar syndrome, without cognitive impairment. There were no further episodes of hepatic failure and serial evaluation showed normal liver function, without evidence of important fibrosis in transient elastography. Genetic analysis revealed that the patient has two novel variants in heterozygosity in TRMU gene, and, in homozygosity, an already known pathogenic variant in SCYL1 gene. Conclusion: Although patient presents neurological features of CALFAN syndrome, it is discussed which genetic disorder (SCYL1 or TRMU) was responsible for the acute liver failure episode.","PeriodicalId":94322,"journal":{"name":"Integrative molecular medicine","volume":"32 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74248629","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SOX30 might not be associated with Sertoli cell-only syndrome in azoospermic Japanese men","authors":"T. Miyamoto, M. Iijima, T. Shin, Masafumi Ikezawa, Yasuhiro Utsuno, Y. Saijo, H. Okada, K. Sengoku","doi":"10.15761/IMM.1000406","DOIUrl":"https://doi.org/10.15761/IMM.1000406","url":null,"abstract":"Purpose: Members of the Sry-related HIGH Motility Group (HMG box (SOX) gene family encode transcription factors that are highly conserved and are critical for a range of developmental processes. In mice, loss of function of the Sox30 gene results in male infertility with failure of spermatogenesis. Here, we investigated the relevance of this gene to human male infertility manifested as Sertoli cell-only syndrome (SCOS) with azoospermia. Methods: A total of 138 Japanese men with SCOS were included, along with 95 fertile Japanese men as healthy controls. All patients underwent testicular microdissection and sperm extraction; however, no spermatozoa were found. Mutation analysis of the SOX30 coding region was performed. Results: Six single nucleotide polymorphisms (SNPs) were identified in the coding region in the patient group. However, the frequency and distribution of SNPs in this allele were not significantly different between patient and control groups. Conclusions: This study suggests a lack of association of SOX30 with azoospermia in infertile Japanese men with SCOS. Here, we describe an analysis of SOX30 single nucleotide polymorphisms (SNPs) in 138 infertile Japanese men showing SCOS.","PeriodicalId":94322,"journal":{"name":"Integrative molecular medicine","volume":"91 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73910414","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of melanocytes in oral mucosa: From embryologic origin to oral mucosal melanoma: A short review","authors":"R. Hsieh, Raquel Silva, S. Lourenço","doi":"10.15761/IMM.1000394","DOIUrl":"https://doi.org/10.15761/IMM.1000394","url":null,"abstract":"Melanoblasts are precursor cells of melanocytes, that arise from neural crest in vertebrates and through several cycles of migration and proliferation, they populate the basal layer of epidermis; hair bulb; eyes; ears and meninges. However, melanocytes also situate in the basal layer of stratified squamous epithelia that is lining in the mouth. The role of melanocytes in the pathophysiology of the oral mucosa still poor understand, and differently from skin melanocytes, they are in a photo-protected site Physiologically, oral melanocytes may or may not produce melanin, however non-physiological alterations related to genetic, metabolic, endocrine, chemical and physical factors, and to infections, inflammatory and neoplasic processes could interfere in the oral pigmentation Primary Oral Mucosal Melanoma (POMM) develops from malignant transformation of melanocytic cell localized in the basal layer of the oral mucosa, which incidence is between 0.2 to 8% of all melanomas, and representing 0.5% of all malignant neoplasias of the oral cavity A better comprehension of the neural crest cells; melanoblasts and melanocytes development and proliferation, and also the melanogenesis and molecular pathways, it could help to understand more about the role of the oral mucosal melanocytes, moreover, and to improve all diagnostic techniques and treatment for Primary Oral Mucosal Melanomas.","PeriodicalId":94322,"journal":{"name":"Integrative molecular medicine","volume":"85 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83918249","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Emerging diagnostic and predictive utilities of natriuretic peptides in diabetes mellitus patients at high cardiovascular risk","authors":"A. Berezin, A. Berezin","doi":"10.15761/IMM.1000393","DOIUrl":"https://doi.org/10.15761/IMM.1000393","url":null,"abstract":"Pre-diabetes and diabetes mellitus (DM) are established cardiovascular (CV) risk factors, which contribute to heart failure (HF) with reduced (HFrEF) and preserved (HFpEF) ejection fraction. Natriuretic peptides (NPs) were found to be useful tool for CV risk stratification among patients with pre-diabetes and T2DM regardless of HF. Previous clinical studies have shown that elevated levels of NPs predicted all-cause and CV mortality, risk of HF manifestation and progression, as well as risk re-admission due to HF. The discriminative potency of NPs for CV death and HF-related events in pre-diabetes and T2DM populations has not been demonstrated beyond traditional CV risk factors. The aim of the review is to accumulate knowledge regarding differential prognostic role of circulating NPs in patients with prediabetes and established T2DM. Presences of HFrEF or HFpEF in T2DM patients may require modification of NP cut-off points to primary diagnose HF and determine HF-related risks. There are several controversies between clinical outcomes and dynamic of circulating levels of NPs in diabetics treated with glucagon-like peptide-1 agonists and sodium-glucose co-transporter-2 inhibitors that requires to be elucidated in large clinical studies in the future.","PeriodicalId":94322,"journal":{"name":"Integrative molecular medicine","volume":"28 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89163182","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phosphoproteomic profile of peripheral blood mononuclear cells in mesangial proliferative glomerulonephritis patients","authors":"Yangyyang Zhang, Guoping Sun, Feng-yan Li, Xiao-cong Lin, Wenbiao Chen, Y. Dai","doi":"10.15761/IMM.1000391","DOIUrl":"https://doi.org/10.15761/IMM.1000391","url":null,"abstract":"To insight the pathogenesis of Mesangial proliferative glomerulonephritis (MsPGN), we investigated the phosphoproteomic profile of PBMCs from MsPGN patients and normal subjects by integrating TiO 2 enrichment technology, 2D nano-liter liquid chromatography and linear ion trap quadrupole mass spectrometry. We identified totally 693 differential phosphorylation sites and corresponded to 439 genes. Gene ontology (GO) analysis showed that protein or nucleic acid binding took up the largest proportion of molecular function, followed by nucleobase, nucleoside, nucleotide and nucleic acid metabolic process in the nucleus. KEGG Pathway analysis showed that most of differential gene enrich in mitogen-activated protein kinase (MAPK) signaling pathway and focal adhesion pathway. Gene network analysis showed that serine/arginine repetitive matrix (SRRM) 1, histone deacetylase (HDAC) 1 and protein kinase C delta (PRKED) were significantly regulators in the network. These results suggested that abnormal changes of protein phosphorylation modification may contribute to MsPGN, and may be derived from the dysregulation of MAPK signaling pathway and focal adhesion pathway. In these pathways, the differential genes SRRM1, HDAC1 and PRKCD with higher connection may be the promising biomarker for MsPGN.","PeriodicalId":94322,"journal":{"name":"Integrative molecular medicine","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82167758","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Quantum chemistry molecular modelling for mitochondria targeted chemotherapy: Verification of oxidative stress on mitochondria and anticancer medicines","authors":"S. Yanagida, S. Yanagisawa, Nobuyuki Murakami","doi":"10.15761/IMM.1000396","DOIUrl":"https://doi.org/10.15761/IMM.1000396","url":null,"abstract":"Background: We understand that most diseases which are accompanied with aging must relate to oxidative stress, i.e. oxidative damage of lipid lamellar bimolecular membranes of mitochondria ( mt ). So-called cancer and tumor are groups of such diseases and are diagnosed on the basis of hard spot touch and cell-deformed invasion image obtained by optical microscope, but molecular-level definition of cancer and tumor cells is unclear. The hard spot and/or the cell invasion will be symptoms relating to metabolic dysfunctions of cells, and hydrogen peroxide-derived hydroxyl radical must induce oxidative degradation of lipid lamellar membranes of mt in the cells. Our goal is to gain insights into reactivity of hydrated HOOH and hydroxyl radicals which produce and exist inevitably in mt , and instability of the mt ’s lipid bimolecular membrane. The result allows us to propose candidates for anticancer medicines which may have antioxidative effects on sustainable mt ’s membranes. Materials and methods: Quantum chemistry molecular modeling, i.e., density functional theory-based molecular modeling (DFT/MM) can be regarded as theory- based “experiments”. DFT/MM can be carried out very quickly using high-end supercomputer-like personal computers. The molecular unit consisting bimolecular membranes is glycerin triester of lauric acid [Gly(n-C 11 H 23 COO) 3 ]. DFT/MM are applicable to molecular aggregates which are induced by van der Waals (vdW) force (i.e. hydrogen bonding and Coulomb interactions). medicines, 5-Fluorouracil, Cisplatin, Oxaliplatin, Vitamin C and thyroid hormone, thyroxine (T4) are verified to suppress oxidation power of HOOH and HO . . DFT/MM verifies that the swelling and/or invasion tissues filled with the swollen and dysfunctional mt is an authentic model of cancer.","PeriodicalId":94322,"journal":{"name":"Integrative molecular medicine","volume":"23 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82000190","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Right ventricular septal or apical? which is optimal positioning in pacemaker implantation: A systematic review and meta-analysis","authors":"Aref Albakri, D. Bimmel","doi":"10.15761/imm.1000411","DOIUrl":"https://doi.org/10.15761/imm.1000411","url":null,"abstract":"","PeriodicalId":94322,"journal":{"name":"Integrative molecular medicine","volume":"77 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81465671","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A meta-analysis of ECG abnormalities (arrhythmias) in different types of heart failure","authors":"Aref Albakri","doi":"10.15761/IMM.1000400","DOIUrl":"https://doi.org/10.15761/IMM.1000400","url":null,"abstract":"The present paper performed a meta-analysis of 11 heart failure (HF) registries and 22 studies (N=292,927; mean age=71.8 years; females=43%) that evaluated arrhythmias in HF. The aim was to determine the prevalence and common types of arrhythmias in different forms of HF. Despite the prevalence of arrhythmias in all forms of heart failure (HF) and their association with a substantial risk of hospitalization, morbidity, and mortality, the search for studies finds that ECG-defined arrhythmias remain an understudied pathology in HF populations. Original studies on arrhythmias in HF populations are lacking, with a majority only reporting atrial fibrillation (AF) and ventricular tachycardia or fibrillation (VT/VF) during index admission as the underlying disease or precipitating factor. VT/VF received disproportionate focus because they confer substantial risk of thromboembolism and sudden cardiac death, respectively. The event rate of AF was 32.7% (95% CI: 31.1-34.3) and VT was 32.0% (95% CI: 12.2-61.3) in the 11 registries and AF occurred in 32.7% (95% CI: 32.5-33.0) in the 22 HF studies. Data on the prevalence of other forms of arrhythmias was either unavailable or insufficient for a pooled analysis. The prevalence of AF was observed in hypertensive HF, HF with reduced/ preserved ejection fraction, right HF, systolic HF, ischemic HF, and thyrotoxic HF. Given that arrhythmias can be both a cause and a consequence of HF, it is important to determine the prevalence of the different types of arrhythmias in different HF populations to improve diagnosis and refine management. Our present findings reveal that studies evaluating VT among HF patients are lacking. The study of ventricular arrhythmias is complicated by its broad-spectrum, which ranges from isolated and asymptomatic ventricular ectopy on ECG to fatal VF. Together with VA's high spontaneous variability, the assessment of the prevalence and incidence of Vas in the HF population becomes extremely difficult, explaining the paucity of studies on VA in HF. However, the VA may be more common in patients with ischemic HF and severely reduced","PeriodicalId":94322,"journal":{"name":"Integrative molecular medicine","volume":"21 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84930902","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Radiosurgery for symptomatic cavernous malformations in the brainstem","authors":"Y. Kida, T. Hasegawa","doi":"10.15761/IMM.1000390","DOIUrl":"https://doi.org/10.15761/IMM.1000390","url":null,"abstract":"Purpose: Cavernous malformations are believed to be clinically silent and some are found just incidentally. However, the lesions once become symptomatic with hemorrhage or epilepsy, they are very troublesome because the repeated episodes may happen. Since the majority of symptomatic incidents of the brainstem lesions are hemorrhage, the prompt treatments are required. Microsurgery has a limited indication such as the lesions easy to access and located just beneath the brainstem surface. It is often difficult and risky to undergo surgery, which requires the skills of the microsurgeon to complete these tasks. Methods and cases: Radiosurgery is an alternative to microsurgery, which has been chosen for treating such symptomatic lesions. Because radiosurgery required no special techniques and can be performed by standard radio surgeons with sufficient knowledge. After the brainstem hemorrhage once or twice, radiosurgery was performed with a mean marginal dose of 12.8 Gy. After the radiosurgery, the follow-up studies were performed at the intervals of every 3 to 6 months. Results: Radiological studies with MRI demonstrated a lesion shrinkage approximately in half of the lesions, and the others showed no obvious change. A few lesions caused hemorrhage showing enlargement of the lesion in the association of clinical signs, even after the treatment. Hemorrhage rate before and after the treatment was considerably decreased from 30 %/year/case to 5 %/year/case after the treatment. Conclusion: Radiosurgery with gamma knife reduced the hemorrhage rate significantly and the lesions were smaller in half and the other half showed no remarkable changes. Since the indication for microsurgery is restricted, radiosurgery is the better treatment option for symptomatic CMs in the brainstem. Radiosurgery might be able to change the natural course of this peculiar disease. Abbreviation: CM: Cavernous malformation; CNS: Central nervous system; HR: Hemorrhage rate; PFS: Progression-free-survival. Introduction Cavernous malformations (CM) are one of the vascular anomalies similar to arteriovenous malformation, venous anomaly and capillary telangiectasia in the central nervous system (CNS). Different from the other three, CMs are a very peculiar disease. The majority of them are usually very silent, however, they become symptomatic all of the sudden in association with repeated hemorrhages and frequent epilepsy attacks. Once becoming symptomatic, they are so troublesome and may develop frequent episodes and neurological deterioration. This is true especially when the brainstem lesions become symptomatic, exclusively with hemorrhage. Motor dysfunction, ataxia, or disturbed ocular movement are the main and popular symptoms of brainstem hemorrhages. Since they may often appear repeatedly, the patients require prompt treatment procedures to stop the bleeding. A waitand-see strategy may be taken into account when the microsurgery is difficult because of the location and the pati","PeriodicalId":94322,"journal":{"name":"Integrative molecular medicine","volume":"23 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82758822","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A meta-analysis of ECG abnormalities (arrhythmia) in cardiomyopathies","authors":"Aref Albakri","doi":"10.15761/IMC.1000140","DOIUrl":"https://doi.org/10.15761/IMC.1000140","url":null,"abstract":"An electrocardiogram (ECG) is an important diagnostic test recommended for individuals with a clinical suspicion of heart disease. The primary diagnostic role is the assessment of the strength and time of electrical activity in the heart. It is also the most common test for the diagnosis of arrhythmias, which are disturbances in the heart rhythm and rate. An ECG test is recommended for patients with cardiomyopathy (CM) and heart failure (HF). The two are distinct but related cardiac disease entities, in which HF is the final sequelae to CM, which is a progressive heart muscle disease. Although arrhythmias are prevalent in both CM and HF, fewer studies have investigated them as the primary objective. In the present pooled analysis of 66 studies (HF=26; CM=40). Atrial fibrillation (AF), ventricular tachycardia (VT) and premature ventricular contractions (PVC) are the most common arrhythmias. The prevalence of AF is higher in HF (32.7%) compared to CM (19.2%) possible due to higher mean age in HF patients (71.8 years) compared to CM (42.7 years) because AF correlates with age. However, the prevalence of VT and PVC is much higher in CM patients (38.0% and 56.6%) compared to HF (3.7% and 13.3%). In both HF and CM, the ECG test is more useful on the differential diagnosis of arrhythmogenic right ventricular cardiomyopathy (ARVC), where it can differentiate ARVC from right ventricular outflow tract induced VT. In addition to diagnostic value, ECG-assessed arrhythmias can guide therapeutic intervention since AF and VT can be life-threatening and may require specific antiarrhythmic therapy.","PeriodicalId":94322,"journal":{"name":"Integrative molecular medicine","volume":"14 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80172361","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}