Integrative molecular medicine最新文献

{"title":"Zika virus and microcephaly: A review of the molecular interactions","authors":"Anne Micaelle Souza Montalvao, Bárbara Rezende Teixeira, R. Andrade, Laura Gomes Lima, E. V. Gomes","doi":"10.15761/IMM.1000392","DOIUrl":"https://doi.org/10.15761/IMM.1000392","url":null,"abstract":"The Zika virus (ZIKV) is a tropical and subtropical emergent pathogen, with main clinical manifestations of low fever, headache, myalgia, arthralgia in the small joints of the hands and feet, non-purulent conjunctivitis, ocular pain, prostration, and pruritic maculopapular rash. Furthermore, the most feared complication of this viral infection is microcephaly, caused by the interaction between ZIKV and cells from the fetal central nervous system (CNS). Identifying the mechanism and factors linked to the entry of ZIKV into human cells, particularly in the fetus during the first developmental months, is currently the greatest challenge in understanding the tropism and pathogenesis of ZIKV. Thus, this review aims to assess the ZIKV–human molecular interaction, the main cellular receptors involved in the virus and host, the viral infection process, and microcephaly neuropathogenesis. During ZIKV–human host interaction, the virus binds to host cell membrane receptors, followed by internalization (through endocytic vesicles) and inhibition of the innate immune response, similar to the normal process of receptor signaling activation. Infection of human fetuses by ZIKV leads to cell cycle deregulation, activating cell death by apoptosis, and microcephaly. Blocking the interaction between the virus and specific membrane receptors may be a good strategy to prevent ZIKV infection, particularly in pregnant women during the first months of fetal development. Thus, knowledge of the whole ZIKV–host interaction process may help in designing novel therapies or targets for drugs to prevent the death of fetal CNS cells and microcephaly.","PeriodicalId":94322,"journal":{"name":"Integrative molecular medicine","volume":"17 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88807381","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":"Comparison of ex-vivo organ culture and cell culture to study drug efficiency and virus-host interactions","authors":"Shay Tayeb, Y. Smith, A. Panet, Z. Zakay‐Rones","doi":"10.15761/imm.1000410","DOIUrl":"https://doi.org/10.15761/imm.1000410","url":null,"abstract":"","PeriodicalId":94322,"journal":{"name":"Integrative molecular medicine","volume":"171 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76942368","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":"COVID-19: Search for Therapeutics","authors":"A. Chakraborty, B. Friedrich, G. TatakeJayant, Vijetha Chiniga, R. Pandey, Preetam Holkar, Neelam Holkar, V. Arora, Randall W. Barton, Anil Diwan","doi":"10.15761/IMM.1000407","DOIUrl":"https://doi.org/10.15761/IMM.1000407","url":null,"abstract":"Human coronaviruses (HCoVs) cause respiratory diseases infecting the upper and/or lower respiratory tract. The six human coronaviruses so far identified are HCoV- 229E, HCoV-OC43, HCoV-NL63, HCoV-HKU-1, SARS-CoV, and MERS-CoV. Four of these coronaviruses (HCoV-229E, HCoV-OC43, HCoV- NL63, and HCoV-HKU-1) are known as circulating common coronavirus found continuously in the human population causing mostly common cold, with few cases of severe diseases. In late December 2019, a novel human coronavirus, now called SARS-CoV-2, was identified during an outbreak in Wuhan, China. The disease spectrum caused by this virus is now called COVID-19 (Coronavirus Infectious disease 2019). This novel coronavirus has spread globally resulting in a world-wide pandemic that continues to rage as of now. SARS-CoV-2 has a high case morbidity and mortality rate and is high risk to the elderly populations, immune-compromised populations, and to those who have other critical issues like heart disease, diabetes, etc. In this review, we summarize the latest information of the epidemiology, pathogenesis, and clinical aspects of SARS-CoV-2, and discuss the current scientific and therapeutic advancements for clinical treatment of this pandemic novel coronavirus.","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":"75365597","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":"α-Klotho and catalase expression in essential hypertension","authors":"G. Pathare, S. Raju, M. Mashru, V. Shah, K. Shalia","doi":"10.15761/IMM.1000395","DOIUrl":"https://doi.org/10.15761/IMM.1000395","url":null,"abstract":"α-Klotho, an anti-aging gene, has emerged as novel inhibitor of oxidative stress at cellular level. α-Klotho inhibits oxidative stress by inhibiting IGF-1/InsulinFOXO (Forkhead box-O transcription factors) dependent deactivation of the antioxidative enzymes. The present study aimed at determining α-Klotho and Catalase gene expressions and Catalase activity in peripheral blood mononuclear cells (PBMCs) of essential hypertensive patients as compared to normotensive healthy controls in Indian population. Forty-eight hypertensives and 48 age, BMI-matched controls were recruited. Gene expression was evaluated by quantitative Real-Time PCR. Catalase enzyme activity in PBMCs and soluble α-Klotho levels in serum were detected using Enzyme-Linked Immunosorbent Assay. Gene expressions for α-Klotho and FOXO1 were significantly low (p<0.001 and p=0.002, respectively) in patients as compared to controls. Catalase expression was also low in hypertensive patients but did not reach statistical significance. However, there was strong positive correlation between ΔCt-based gene expression of α-Klotho and Catalase in patients (p<0.001) as well as controls (p=0.008). Positive correlation was also observed between gene expression of FOXO1 and that of α-Klotho (p=0.006) and Catalase (p=0.001) in hypertensives. Catalase activity in patients were significantly low (p<0.001) as compared to controls and positively correlated with soluble α-Klotho levels (rs=0.32, p=0.027), which were also 30.2% lower (p<0.001) in the patient group. Present study demonstrates low soluble levels and gene expression of anti-aging protein α-Klotho in hypertensive patients. α-Klotho may influence Catalase expression in essential hypertension through its effect on FOXO1 expression.","PeriodicalId":94322,"journal":{"name":"Integrative molecular medicine","volume":"35 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81289645","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 changing molecular landscape of AML and its impact on treatment","authors":"L. Finn, C. Davis, Michael J Lunski, Muhammad Azeem Khan, A. Staton, Ambuga R. Badari","doi":"10.15761/IMM.1000405","DOIUrl":"https://doi.org/10.15761/IMM.1000405","url":null,"abstract":"Acute myeloid leukemia is the primary acute leukemia affecting adults and until recently had very limited available treatment options. We are now seeing development and redevelopment of targeted therapy in acute myeloid leukemia with subsequent improvements in disease control and overall survival. The development of therapy with molecular targets allows patients who are not candidates for chemotherapy to receive treatment. In this review, we discuss the molecular mutations FLT3 and IDH and the molecular target CD33, recognized for having key roles in the development of acute myeloid leukemia. We reference key clinical trials to further discuss the approved treatments for acute myeloid leukemia that target these molecular mutations. We then discuss ongoing research to develop new drugs and new combinations of therapy to overcome resistance mechanisms and further improve patient outcomes.","PeriodicalId":94322,"journal":{"name":"Integrative molecular medicine","volume":"186 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88508463","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":"Potential roles of nitric oxide in COVID-19: A perspective","authors":"A. Mel","doi":"10.15761/IMM.1000403","DOIUrl":"https://doi.org/10.15761/IMM.1000403","url":null,"abstract":"Coronavirus disease 2019 (COVID-19) is a respiratory tract infection caused by a beta-coronavirus closely linked to the SARS coronavirus. COVID-19 patients present with hypoxemia linked to acute respiratory distress syndrome (ARDS). Reversing the hypoxemia prevalent in COVID-19 requires advanced mechanisms that facilitate the transportation of oxygen from alveoli to blood, as increased supplemental oxygen does not always lead to optimal oxygen saturation. Clinical and experimental evidence suggest a significant role for inhaled Nitric Oxide (NO) as a selective vasodilator, which has shown to restore oxygenation by helping to normalise shunts and ventilation/perfusion mismatch. NO has demonstrated the ability to suppress the replication of a respiratory corona virus, which is unique for NO among other vasodilators. These suggest a potentially significant role for NO in the clinical management of COVID-19, warranting urgent investigations into optimal methods of harnessing its potential in restoring pulmonary physiology. Introduction The pathophysiological conditions and clinical evidence associated with COVID-19 are rapidly being established, supporting the development of therapeutic solutions [1,2]. COVID-19 patients present with respiratory characteristics of acute respiratory distress syndrome (ARDS), which in accordance with The Berlin definition includes; new or worsening respiratory symptoms within one week of symptom onset; bilateral opacities on chest imaging not fully explained by effusions, atelectasis or nodules; respiratory failure from lung edema not fully explained by cardiac failure or fluid overload; and finally oxygenation impairment [3]. However, the ARDS presented with COVID-19 is recognised to be atypical as an alarmingly majority do not experience breathlessness and have relatively good lung compliance, whilst presenting with hypoxia [4-6]. Supplemental oxygen can partially improve oxygen saturation. However, hypoxaemia due to shunt does not respond well to supplemental oxygen [7]. High levels of supplemental oxygen can be toxic but can be prevented by titrating [8]. Invasive mechanical ventilation, which is considered when addressing the most severe cases continues to be associated with a higher incidence of adverse outcomes [9]. Therefore, there is currently an incentive to explore alternative methods of optimal management of patients in addition to widely practiced prone positioning [10]. Methods of reducing pulmonary resistance and resolving oxygenation with noninvasive therapy are of interest [11]. Hypoxia is known to cause vasodilation in systemic arteries whilst causing vasoconstriction in pulmonary arterioles. Nitric Oxide (NO) has a major role in regulating hypoxia and in healthy conditions it was found that NO can mediate adaptive mechanisms including modulation of vasodilation. Hypoxia regulation in extreme conditions such as high altitudes has shown a strong link to NO, with large populationbased studies demonstrat","PeriodicalId":94322,"journal":{"name":"Integrative molecular medicine","volume":"37 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81125533","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":"Superoxide dismutase, glutathione peroxidase and catalase activities in patients with viral hepatitis C","authors":"Yalcin Ms, Gulesci N, Bilgin R, Koltas Is","doi":"10.15761/IMM.1000397","DOIUrl":"https://doi.org/10.15761/IMM.1000397","url":null,"abstract":"Purpose: Aerobic organisms possess antioxidant defense systems that deal with reactive oxygen species (ROS) produced as a consequence of aerobic respiration and substrate oxidation. It is considered that free radicals, lipid peroxidation and antioxidant defense play a role in various tissue damages, just as in certain types of viral hepatitis. Materials and methods: We determined SOD, CAT, GPX activities of 18 HCV subjects and matched their values with that of 18 healthy volunteers as control. The patients were diagnosed by physicians on the basis of detailed clinical history, clinical examination and other relevant biochemical investigations. Results: SOD, CAT and GPX activities in patients with HCV were found as (mean±SD) 2.75±0.75 U/mg prot, 19.25±3.4 U/g Hbx10 4 , 78.25±23.23 U/g Hb respectively, whereas for the control group 3.76±1.53 U/mg prot, 13.71±1.6 U/g Hbx10 4 , 63.26±6.9 U/g Hb were observed for the respective enzymes. Conclusion: Our results show the mild impact of hepatitis C on antioxidant status of the person. There is a reduction in SOD level but an increase in CAT and GPX levels. In this study also suggests some possible role of oxidative stress in the mechanism of liver injury during viral hepatitis.","PeriodicalId":94322,"journal":{"name":"Integrative molecular medicine","volume":"63 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80123120","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":"Inflammatory cardiomyopathy: A review and meta-analysis of pathophysiology, diagnosis and clinical management","authors":"Aref Albakri","doi":"10.15761/IMM.1000404","DOIUrl":"https://doi.org/10.15761/IMM.1000404","url":null,"abstract":"Inflammatory cardiomyopathy (ICM) is a serious long-term sequelae of myocarditis (MC), defined as the inflammation of the heart muscle accompanied by cardiac dysfunction. Definitive diagnosis of ICM remains a challenge due to the lack of pathognomonic clinical signs and symptoms, as well as the disease mimics a variety of other non-inflammatory myocardial diseases. The disease has multiple aetiologies including infectious, autoimmune, drugs and toxins. Diagnosis relies on histological, immunological, immunohistochemical and molecular findings of infectious causes and the evidence of cardiac dysfunction. Whereas endomyocardial biopsy is the diagnostic gold standard for MC and ICM as well as distinguishes aetiological forms, its use in routine clinical setting is infrequent. The result is the lack of certainty in the epidemiological impact and the natural history of ICM. Moreover, ICM may resolve spontaneously, recur or become chronic leading to death or the need for cardiac transplantation. Traditional diagnosis based on the Dallas Criteria considered MC a relatively rare cause of ICM, HF and sudden cardiac death. However, the recent use of highly sensitive immunohistochemical and molecular tools applied to EMB together with advances in non-invasive imaging modalities suggest the prevalence of the MC and ICM could be much higher than previously estimated. Therefore, the present study reviews published literature on the epidemiology, aetiology, pathophysiology, diagnosis and clinical management to broaden understanding of this potentially treatable but life-threatening disease entity.","PeriodicalId":94322,"journal":{"name":"Integrative molecular medicine","volume":"4 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83681629","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":"Brain metastasis in HER2 positive stomach cancer","authors":"Y. Cihan","doi":"10.15761/IMM.1000402","DOIUrl":"https://doi.org/10.15761/IMM.1000402","url":null,"abstract":"","PeriodicalId":94322,"journal":{"name":"Integrative molecular medicine","volume":"3 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88736700","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":"NL63: A Better Surrogate Virus for studying SARS-CoV-2","authors":"A. Chakraborty, Anil Diwan","doi":"10.15761/imm.1000408","DOIUrl":"https://doi.org/10.15761/imm.1000408","url":null,"abstract":"","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":"79924097","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}