Recent patents on endocrine, metabolic & immune drug discovery最新文献

{"title":"Reduction of hyperproduction of thyroid autoantibodies in patients without disturbance of the thyroid function: new patents.","authors":"Borys A Gerasun,&nbsp;Olga A Holubovska,&nbsp;Roman Y Hrytsko,&nbsp;Olexandr N Zinchuk,&nbsp;Andrij V Shkurba","doi":"10.2174/1872214808666140604144552","DOIUrl":"https://doi.org/10.2174/1872214808666140604144552","url":null,"abstract":"<p><strong>Unlabelled: </strong>A new method of reduction of autoimmune process activity related to the thyroid in patients without signs of thyroiditis is presented in the article (patent of Ukraine No. 103742). New patents and inventions from different countries of the world related to the problem have been analysed.</p><p><strong>Materials and methods: </strong>Sixty one patients with a significant disturbance of tolerance to the thyroid antigens in the absence of disturbance of the thyroid function were involved in the research. Twenty two patients with chronic hepatitis C, genotype 1 HCV, receiving antiviral therapy, were also included in the research. Patients were immunized intracutaneously with autoleukocytes for autoimmune process inhibition. After single immunization with autoleukocytes decrease in the level of antibodies against the thyroid antigens was observed in all patients. In some patients without chronic hepatitis C the levels of thyroperoxidase and thyroglobulin antibodies decreased by 50% and more (33.33% and 20.51%, respectively). In patients with ChHC these indices were considerably lower, and the duration of the achieved effect was shorter. However, immunization inhibited activity of immune process in patients with ChHC due to interferon therapy. The suggested method enables to decrease the threat for thyroiditis development even in patients with chronic hepatitis C during antiviral therapy.</p>","PeriodicalId":89474,"journal":{"name":"Recent patents on endocrine, metabolic & immune drug discovery","volume":"8 2","pages":"140-5"},"PeriodicalIF":0.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32429709","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":"Cognitive function and quality of life in mild thyroid hormone deficiency.","authors":"Sara Tognini,&nbsp;Giuseppe Pasqualetti,&nbsp;Valeria Calsolaro,&nbsp;Antonio Polini,&nbsp;Fabio Monzani","doi":"10.2174/1872214808666140723111533","DOIUrl":"https://doi.org/10.2174/1872214808666140723111533","url":null,"abstract":"<p><p>Subclinical hypothyroidism (sHT) is very common in general population, especially in women and older people. sHT individuals may experience symptoms that resemble those observed in overt hypothyroidism, resulting in impaired quality of life (QOL). Asymptomatic patients may suffer a reduction in perceived health status due to the awareness of disease. Cognitive function represents one of the most important domains of the QOL questionnaires. Given the intrinsic relationship between cognitive status and QOL it is worth to address these topics together, in a systematic review of the literature. Thus, we reviewed the English scientific literature available on National Library of Medicine (www.pubmed.com) sine 1980 regarding hypothyroidism, sHT, elderly, L-thyroxine (LT4) therapy, QOL, cognition, brain. We supplemented the search with records from personal files, textbooks, and relevant articles. The possible link, at molecular level, between cognition and thyroid failure was also assessed. Conflicting results on the association between sHT and cognitive and health related QOL impairment are still present, although the most recent, naturalistic studies did not find any significant relationship. Interestingly, a reduction in health related QOL is frequently reported in patients with thyroid autoimmune diseases regardless of thyroid dysfunction. We also report most significant patents on the topic. </p>","PeriodicalId":89474,"journal":{"name":"Recent patents on endocrine, metabolic & immune drug discovery","volume":"8 2","pages":"124-34"},"PeriodicalIF":0.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32527828","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":"Impaired clearance of neutrophils extracellular trap (NET) may induce detrimental tissular effect.","authors":"Paula M F Anjos,&nbsp;Fernanda S Fagundes-Netto,&nbsp;Caroline M O Volpe,&nbsp;Jose A Nogueira-Machado","doi":"10.2174/1872214808666141015120450","DOIUrl":"https://doi.org/10.2174/1872214808666141015120450","url":null,"abstract":"<p><p>Neutrophils Extracellular Trap (NET) is composed of nuclear chromatin with hyper segmentation of nuclear lobes, citrullination of histone-associated DNA and mixing with cytoplasmic proteins including the enzyme myeloperoxidase. It is believed that neutrophils trap can kill microorganisms and constitutes a new form of innate defense. However, in some conditions, NET formation may be detrimental to the organism due to its association with autoantibody formation. Thus, NETs can be beneficial or detrimental depending of the DNA clearance recent registered patents describing the processes, products, methods and therapeutic indications of the neutrophil extracellular trap (NET) phenomenon have been reported. The patents US8710039; EP2465536; EP2651440; US20130302345; US20140099648; US20130183662; WO2012166611; and RU2463349C2, related to NETosis, suggest an association between NET formation and autoimmunity. However, its function is still not fully understood. Some parasites have learned to escape from NET using nucleases. NET persistence could be due to a possible enzymatic inhibition as suggested in Grabar´s theory for explaining the induction of physiologic or pathologic autoantibodies. In the present mini-review NET persistence due to impairment in the homeostasis clearance of DNA is discussed. </p>","PeriodicalId":89474,"journal":{"name":"Recent patents on endocrine, metabolic & immune drug discovery","volume":"8 3","pages":"186-90"},"PeriodicalIF":0.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32747665","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":"Modelling of human leucyl aminopeptidases for in silico off target binding analysis of potential Plasmodium falciparum leucine aminopeptidase (PfA-M17) specific inhibitors.","authors":"Shakti Sahi,&nbsp;Utkarsh Raj,&nbsp;Meenakshi Chaudhary,&nbsp;Vikrant Nain","doi":"10.2174/1872214808666141001125057","DOIUrl":"https://doi.org/10.2174/1872214808666141001125057","url":null,"abstract":"<p><p>Malaria is one of the most widespread infectious diseases in the world. Emergence of multi-drug resistant Plasmodium strains makes it crucial to identify new classes of compounds for anti-malarial therapy. Novel anti-malarial compounds from natural sources (Gomphostema niveum) as well as synthetic chemicals (5-aminolevulinic acid) have been reported in recent patents. Plasmodium falciparum leucyl aminopeptidase (PfA-M17) is a validated target for antimalarial drug development. However, known aminopeptidase inhibitors beset with the problem of non-specificity. Therefore, 3D structural models of PfA-M17 human homologs, Leucine aminopeptidase3 (hLAP3) and probable leucine aminopeptidase (hNPEPL1) were predicted for molecular docking based screening of potential inhibitors for their off target activity. Comparison of IC50 and docking scores of highly active hLAP3 inhibitors shows good correlation (r(2)≈ 0.8). Further, docking analysis with potential PfA-M17 inhibitor Compound-X (identified through virtual screening) shows much higher binding affinity towards PfA-M17 (docking score -11.44) than hLAP3 (docking score -4.26) and hNPEPL1 (docking score -5.08). This lead compound, Compound-X can act as a scaffold for further increasing PfA-M17 binding affinity and hLAP3 and hNPEPL1 3D structure models will be useful for screening of PfA-M17 specific inhibitors. </p>","PeriodicalId":89474,"journal":{"name":"Recent patents on endocrine, metabolic & immune drug discovery","volume":"8 3","pages":"191-201"},"PeriodicalIF":0.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32707584","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":"Recent patents on light based therapies: photodynamic therapy, photothermal therapy and photoimmunotherapy.","authors":"Emilio J Sanchez-Barcelo,&nbsp;Maria D Mediavilla","doi":"10.2174/1872214807666131229103707","DOIUrl":"https://doi.org/10.2174/1872214807666131229103707","url":null,"abstract":"<p><p>This article reviews the more recent patents in three kinds of therapeutic strategies using the application of visible light to irradiate photosensible substances (PSs) of different natures. The light-activation of these PSs is directly responsible for the desired therapeutic effects. This group of light therapies includes photodynamic therapy (PDT), photothermal therapy (PTT) and photoimmunotherapy (PIT). Therapeutic mechanisms triggered by the activation of the PSs depend basically (though not exclusively) on the release of reactive oxygen species (ROS) and the activation of immune responses (PDT and PIT) or the local generation of heat (PTT). The main difference between PIT and PDT is that in PIT, monoclonal antibodies (MABs) are associated to PSs to improve the selective binding of the PSs to the target tissues. All these therapeutic strategies offer the possibility of destroying tumor tissue without damaging the surrounding healthy tissue, which is not achievable with chemotherapy or radiotherapy. PDT is also used as an alternative or adjuvant antimicrobial therapy together with the traditional antibiotic therapy since these organisms are unlikely to develop resistance to the ROS induced by PDT. Furthermore, PDT also induces an immune response against bacterial pathogens. The current challenge in PDT, PIT and PTT is to obtain the highest level of selectivity to act on targeted sick tissues with the minimum effects on the surrounding healthy tissue. The development of new PSs with high affinity for specific tissues, new PSs- MABs conjugates to bind to specific kinds of tumors, and new light-sensible nanoparticles with low toxicity, will increase the clinical utility of these therapies. </p>","PeriodicalId":89474,"journal":{"name":"Recent patents on endocrine, metabolic & immune drug discovery","volume":"8 1","pages":"1-8"},"PeriodicalIF":0.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/1872214807666131229103707","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31984716","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":"Recent methods for assessing osteoporosis and fracture risk.","authors":"Kazuhiro Imai","doi":"10.2174/1872214808666140118223801","DOIUrl":"https://doi.org/10.2174/1872214808666140118223801","url":null,"abstract":"<p><p>In the management and treatment of osteoporosis, the target is to assess fracture risk and the end-point is to prevent fractures. Traditionally, measurement of bone mineral density (BMD) by dual energy X-ray absorptiometry (DXA) has been the standard method for diagnosing osteoporosis, in addition to assessing fracture risk and therapeutic effects. Quantitative computed tomography (QCT) can quantify volumetric BMD, and cancellous bone can be measured independently of surrounding cortical bone and aortic calcification. Hip structure analysis (HSA) is a method using the DXA scan image and provides useful data for assessing hip fracture risk. Recently, new tools to assess osteoporosis and fracture risk have been developed. One of the recent advances has been the development of the FRAX (Fracture Risk Assessment Tool), which is helpful in conveying fracture risk to patients and providing treatment guidance to clinicians. Another advance is the finite element (FE) method based on data from computed tomography (CT), which is useful for assessing bone strength, fracture risk, and therapeutic effects on osteoporosis. In selecting the most appropriate drug for osteoporosis treatment, assessment by bone metabolic markers is an important factor. In this review, recent patents for assessing osteoporosis and fracture risk are discussed. </p>","PeriodicalId":89474,"journal":{"name":"Recent patents on endocrine, metabolic & immune drug discovery","volume":"8 1","pages":"48-59"},"PeriodicalIF":0.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/1872214808666140118223801","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32041272","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":"Effects of melatonin derivatives on human malaria parasite Plasmodium falciparum.","authors":"Venkataramanujan Srinivasan,&nbsp;Rahimah Zakaria,&nbsp;Mahaneem Mohamed,&nbsp;Rozieyati M Saleh","doi":"10.2174/1872214808666140616143623","DOIUrl":"https://doi.org/10.2174/1872214808666140616143623","url":null,"abstract":"<p><p>Melatonin's function in modulating the circadian cycle of Plasmodium falciparum has been an intense investigation for the past 45 years. The stimulatory effects of melatonin on malaria growth, development and differentiation have been confirmed by numerous studies conducted in the past 40 years but the molecular mechanisms underlying melatonin stimulatory effects have been well understood recently. Melatonin has been identified as a \"signal\" essential for synchronization of malaria parasitic cell cycle. Melatonin has been shown to modulate the release of intracellular Ca²⁺ and cAMP in Plasmodium falciparum. In this context, melatonin receptor blocking agent luzindole has been shown to block melatonin's actions in these intracellular events occurring in human malaria parasites. Recent studies have resulted in the synthesis and development of melatonin derivatives, compounds 7-11 and 12-16. Of these compounds 12, 13 and 14 were able to inhibit the Plasmodium falciparum growth and this serves as a promising lead for the development of future antimalarial compounds that will have rapid antimalarial actions with low toxicity. Some antimalarial drugs that have been patented are also summarized in this review.</p>","PeriodicalId":89474,"journal":{"name":"Recent patents on endocrine, metabolic & immune drug discovery","volume":"8 2","pages":"102-8"},"PeriodicalIF":0.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32428545","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 two faces of protein palmitoylation in islet β-cell function: potential implications in the pathophysiology of islet metabolic dysregulation and diabetes.","authors":"Abiy M Mohammed,&nbsp;Fei Chen,&nbsp;Anjaneyulu Kowluru","doi":"10.2174/18722148113079990008","DOIUrl":"https://doi.org/10.2174/18722148113079990008","url":null,"abstract":"<p><p>Several cellular proteins undergo post-translational lipidation, including prenylation, palmitoylation and myristoylation, which are felt to promote intracellular targeting, membrane association and interaction with effector partner proteins. Recent findings implicate definitive roles of isoprenylation in islet β-cell function including glucose-stimulated insulin secretion [GSIS]. Published evidence also suggests novel regulatory roles for protein palmitoylation not only in GSIS but also in the metabolic dysfunction induced by proinflammatory cytokines and lipotoxic conditions. Herein, we overviewed the existing evidence on the regulatory roles of protein palmitoylation in the metabolic [dys]regulation of the islet β-cell and highlighted the developments in this area, specifically on potential identity of palmitoylated proteins, and on the utility of two structurally distinct inhibitors of palmitoylation [e.g., cerulenin and 2-bromopalmitate] in halting the metabolic dysfunction of the islet β-cell known to occur following exposure to proinflammatory cytokines and lipotoxic conditions. Potential avenues for future research, including the immediate need for discovery of novel small molecule compounds as inhibitors of palmitoyl transferases to attenuate deleterious consequences of proinflammatory cytokines and glucolipotoxicity are discussed. Furthermore, some relevant patents are also highlighted in this review. </p>","PeriodicalId":89474,"journal":{"name":"Recent patents on endocrine, metabolic & immune drug discovery","volume":"7 3","pages":"203-12"},"PeriodicalIF":0.0,"publicationDate":"2013-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31203102","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":"Associations between periodontitis and systemic inflammatory diseases: response to treatment.","authors":"Una El-Shinnawi,&nbsp;Mena Soory","doi":"10.2174/18715303113139990040","DOIUrl":"https://doi.org/10.2174/18715303113139990040","url":null,"abstract":"<p><p>There is a significant prevalence of subjects with periodontitis presenting with other inflammatory conditions such as coronary heart disease, insulin resistance and arthritis. This pattern of disease presentation underscores the importance of inflammatory loading from chronic diseases, in driving their pathogeneses in a multidirectional manner. Pro-inflammatory cytokines and other agents play an important role in this process; for example, a single nucleotide polymorphism of the TNF-α gene is associated with significant periodontal attachment loss in patients with coronary heart disease. Changes in gene expression associated with inflammation and lipid metabolism in response to oral infection with the periodontal pathogen Porphyromonas gingivalis (Pg) have been demonstrated in mouse models, independent of the demonstration of atherosclerotic lesions. Insulin resistance is considered to be a chronic low-grade inflammatory condition, associated with altered glucose tolerance, hypertriglyceridemia, central obesity and coronary heart disease. It is accompanied by elevated levels of IL-1, IL-6 and TNF-α also relevant to the progression of periodontitis. There is evidence that uncontrolled periodontal disease contributes to maintenance of systemic diseases, including rheumatoid arthritis (RA), with increased risk of periodontitis in subjects with RA. The periodontal pathogen Pg is significant in contributing to citrullination of proteins resulting in immune dysregulation and autoimmune responses, seen in RA. However, they are both multifactorial chronic diseases with complex etiopathogeneses that affect their presentation. Consistent but weak associations are seen for surrogate markers of periodontitis such as tooth loss, with multiple systemic conditions. Effective treatment of periodontitis would be important in reducing systemic inflammatory loading from chronic local inflammation and in achieving systemic health. Lack of a consistent cause and effect relationship in all subjects would be influenced by genetic, epigenetic and other subject variables, although there are clear mechanisms that link the associations. This article includes an appraisal of patents and their applications. </p>","PeriodicalId":89474,"journal":{"name":"Recent patents on endocrine, metabolic & immune drug discovery","volume":"7 3","pages":"169-88"},"PeriodicalIF":0.0,"publicationDate":"2013-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31626744","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 anti-oxidant properties of isothiocyanates: a review.","authors":"Sônia M de Figueiredo,&nbsp;Sidney A V Filho,&nbsp;José A Nogueira-Machado,&nbsp;Rachel B Caligiorne","doi":"10.2174/18722148113079990011","DOIUrl":"https://doi.org/10.2174/18722148113079990011","url":null,"abstract":"<p><p>Cruciferous vegetables, such as broccoli and watercress, have been studied extensively aiming to evaluate their chemopreventive properties. Some of them have already been established using animal models. The ITCs induce Phase II enzymes related to detoxification processes of chemical carcinogens to prevent the start of carcinogenesis. They also exhibit antitumor activity at post-initiation phase, suggesting their additional role(s) in cancer prevention. Sulforaphane is the most extensively studied isothiocyanate, focused in its anti-tumoral activity and it is mainly found in great amounts in broccoli and other cruciferous. In a dose dependent manner, ITCs inhibit the cell viability of human cervical cancer cells, human pancreatic cancer cells, human hepatocellular carcinoma cells, human ovarian cancer cells, and have antiinflammatory properties in the treatment of human T-cell leukemia cells. This protective effect may be due to improved antioxidant status. Although the health effects of diet in humans are generally considered promising, there are definite challenges and limitations of the current data in better understanding of the molecular mechanisms responsible for this effect, together with the possible interactions between different dietary constituents. The survey of relevant patents on the use of isothiocyanates such as sulforaphane for cancer and cardiovascular diseases treatments is also included in this review. </p>","PeriodicalId":89474,"journal":{"name":"Recent patents on endocrine, metabolic & immune drug discovery","volume":"7 3","pages":"213-25"},"PeriodicalIF":0.0,"publicationDate":"2013-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31684970","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}