Biomolecular Concepts最新文献

{"title":"Insulin resistance is positively associated with plasma cathepsin D activity in NAFLD patients.","authors":"Lingling Ding,&nbsp;Toon J I De Munck,&nbsp;Yvonne Oligschlaeger,&nbsp;Jef Verbeek,&nbsp;Ger H Koek,&nbsp;Tom Houben,&nbsp;Ronit Shiri-Sverdlov","doi":"10.1515/bmc-2021-0011","DOIUrl":"https://doi.org/10.1515/bmc-2021-0011","url":null,"abstract":"<p><p>Previous studies associated plasma cathepsin D (CTSD) activity with hepatic insulin resistance in overweight and obese humans. Insulin resistance is a major feature of non-alcoholic fatty liver disease (NAFLD) and is one of the multiple hits determining the progression towards non-alcoholic steatohepatitis (NASH). In line, we have previously demonstrated that plasma CTSD levels are increased in NASH patients. However, it is not known whether insulin resistance associates with plasma CTSD activity in NAFLD. To increase our understanding regarding the mechanisms by which insulin resistance mediates NAFLD, fifty-five liver biopsy or MRI-proven NAFLD patients (BMI>25kg/m²) were included to investigate the link between plasma CTSD activity to insulin resistance in NAFLD. We concluded that HOMA-IR and plasma insulin levels are independently associated with plasma CTSD activity in NAFLD patients (standardized coefficient β: 0.412, 95% Cl: 0.142~0.679, p=0.004 and standardized coefficient β: 0.495, 95% Cl: 0.236~0.758, p=0.000, respectively). Together with previous studies, these data suggest that insulin resistance may link to NAFLD via elevation of CTSD activity in plasma. As such, these data pave the way for testing CTSD inhibitors as a pharmacological treatment of NAFLD.</p>","PeriodicalId":38392,"journal":{"name":"Biomolecular Concepts","volume":" ","pages":"110-115"},"PeriodicalIF":0.0,"publicationDate":"2021-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39294457","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":"Retraction of: Alzheimer's and Danish dementia peptides induce cataract and perturb retinal architecture in rats.","authors":"G Bhanuprakash Reddy,&nbsp;P Yadagiri Reddy,&nbsp;Avadhesha Surolia","doi":"10.1515/bmc-2021-0012","DOIUrl":"https://doi.org/10.1515/bmc-2021-0012","url":null,"abstract":"and Danish dementia peptides induce cataract and perturb retinal in","PeriodicalId":38392,"journal":{"name":"Biomolecular Concepts","volume":" ","pages":"116"},"PeriodicalIF":0.0,"publicationDate":"2021-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1515/bmc-2021-0012","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39263802","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":"Bcl2 negatively regulates Protective Immune Responses During <i>Mycobacterial</i> Infection.","authors":"Aayushi Singh,&nbsp;Vandana Anang,&nbsp;Chaitenya Verma,&nbsp;Shakuntala Surender Kumar Saraswati,&nbsp;Ankush Kumar Rana,&nbsp;Upasana Bandyopadhyay,&nbsp;Attinder Chadha,&nbsp;Krishnamurthy Natarajan","doi":"10.1515/bmc-2021-0010","DOIUrl":"https://doi.org/10.1515/bmc-2021-0010","url":null,"abstract":"<p><p>We previously reported that <i>M. tb</i> on its own as well as together with HIV inhibits macrophage apoptosis by upregulating the expression of Bcl2 and Inhibitor of Apoptosis (IAP). In addition, recent reports from our lab showed that stimulation of either macrophages or BMDCs results in the significant upregulation of Bcl2. In this report, we delineate the role of Bcl2 in mediating defense responses from dendritic cells (BMDCs) during mycobacterial infection. Inhibiting Bcl2 led to a significant decrease in intracellular bacterial burden in BMDCs. To further characterize the role of Bcl2 in modulating defense responses, we inhibited Bcl2 in BMDCs as well as human PBMCs to monitor their activation and functional status in response to mycobacterial infection and stimulation with <i>M. tb</i> antigen Rv3416. Inhibiting Bcl2 generated protective responses including increased expression of co-stimulatory molecules, oxidative burst, pro-inflammatory cytokine expression and autophagy. Finally, co-culturing human PBMCs and BMDCs with antigen-primed T cells increased their proliferation, activation and effector function. These results point towards a critical role for Bcl2 in regulating BMDCs defense responses to mycobacterial infection.</p>","PeriodicalId":38392,"journal":{"name":"Biomolecular Concepts","volume":" ","pages":"94-109"},"PeriodicalIF":0.0,"publicationDate":"2021-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1515/bmc-2021-0010","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39218436","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":"Incidence and characterisation of <i>Bacillus cereus</i> bacteriophages from Thua Nao, a Thai fermented soybean product.","authors":"Wallapat Phongtang, Ekachai Chukeatirote","doi":"10.1515/bmc-2021-0009","DOIUrl":"10.1515/bmc-2021-0009","url":null,"abstract":"<p><p><i>Bacillus cereus</i> is considered to be an important food poisoning agent causing diarrhea and vomiting. In this study, the occurrence of <i>B. cereus</i> bacteriophages in Thai fermented soybean products (Thua Nao) was studied using five <i>B. cereus sensu lato</i> indicator strains (four <i>B. cereus</i> strains and one <i>B. thuringiensis</i> strain). In a total of 26 Thua Nao samples, there were only two bacteriophages namely BaceFT01 and BaceCM02 exhibiting lytic activity against <i>B. cereus</i>. Morphological analysis revealed that these two bacteriophages belonged to the <i>Myoviridae</i>. Both phages were specific to <i>B. cereus</i> and not able to lyse other tested bacteria including <i>B. licheniformis</i> and <i>B. subtilis</i>. The two phages were able to survive in a pH range between 5 and 12. However, both phages were inactive either by treatment of 50°C for 2 h or exposure of UV for 2 h. It should be noted that both phages were chloroform-insensitive, however. This is the first report describing the presence of bacteriophages in Thua Nao products. The characterization of these two phages is expected to be useful in the food industry for an alternative strategy including the potential use of the phages as a biocontrol candidate against foodborne pathogenic bacteria.</p>","PeriodicalId":38392,"journal":{"name":"Biomolecular Concepts","volume":" ","pages":"85-93"},"PeriodicalIF":0.0,"publicationDate":"2021-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1515/bmc-2021-0009","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39147460","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":"Size-based Degradation of Therapeutic Proteins - Mechanisms, Modelling and Control.","authors":"Rohit Bansal,&nbsp;Saurabh Kumar Jha,&nbsp;Niraj Kumar Jha","doi":"10.1515/bmc-2021-0008","DOIUrl":"https://doi.org/10.1515/bmc-2021-0008","url":null,"abstract":"<p><p>Protein therapeutics are in great demand due to their effectiveness towards hard-to-treat diseases. Despite their high demand, these bio-therapeutics are very susceptible to degradation <i>via</i> aggregation, fragmentation, oxidation, and reduction, all of which are very likely to affect the quality and efficacy of the product. Mechanisms and modelling of these degradation (aggregation and fragmentation) pathways is critical for gaining a deeper understanding of stability of these products. This review aims to provide a summary of major developments that have occurred towards unravelling the mechanisms of size-based protein degradation (particularly aggregation and fragmentation), modelling of these size-based degradation pathways, and their control. Major caveats that remain in our understanding and control of size-based protein degradation have also been presented and discussed.</p>","PeriodicalId":38392,"journal":{"name":"Biomolecular Concepts","volume":" ","pages":"68-84"},"PeriodicalIF":0.0,"publicationDate":"2021-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1515/bmc-2021-0008","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39248189","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":"Pathophysiological Aspects of the Development of Abdominal Aortic Aneurysm with a Special Focus on Mitochondrial Dysfunction and Genetic Associations.","authors":"Volha I Summerhill,&nbsp;Vasily N Sukhorukov,&nbsp;Ali H Eid,&nbsp;Ludmila V Nedosugova,&nbsp;Igor A Sobenin,&nbsp;Alexander N Orekhov","doi":"10.1515/bmc-2021-0007","DOIUrl":"https://doi.org/10.1515/bmc-2021-0007","url":null,"abstract":"<p><p>Abdominal aortic aneurysm (AAA) is a complex degenerative vascular disease, with considerable morbidity and mortality rates among the elderly population. The mortality of AAA is related to aneurysm expansion (the enlargement of the aortic diameter up to 30 mm and above) and the subsequent rupture. The pathogenesis of AAA involves several biological processes, including aortic mural inflammation, oxidative stress, vascular smooth muscle cell apoptosis, elastin depletion, and degradation of the extracellular matrix. Mitochondrial dysfunction was also found to be associated with AAA formation. The evidence accumulated to date supports a close relationship between environmental and genetic factors in AAA initiation and progression. However, a comprehensive pathophysiological understanding of AAA formation remains incomplete. The open surgical repair of AAA is the only therapeutic option currently available, while a specific pharmacotherapy is still awaited. Therefore, there is a great need to clarify pathophysiological cellular and molecular mechanisms underlying AAA formation that would help to develop effective pharmacological therapies. In this review, pathophysiological aspects of AAA development with a special focus on mitochondrial dysfunction and genetic associations were discussed.</p>","PeriodicalId":38392,"journal":{"name":"Biomolecular Concepts","volume":" ","pages":"55-67"},"PeriodicalIF":0.0,"publicationDate":"2021-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1515/bmc-2021-0007","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39102978","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":"Polyphenols from Passiflora ligularis Regulate Inflammatory Markers and Weight Gain.","authors":"Jaime Angel-Isaza,&nbsp;Juan Carlos Carmona-Hernandez,&nbsp;William Narváez-Solarte,&nbsp;Clara Helena Gonzalez-Correa","doi":"10.1515/bmc-2021-0005","DOIUrl":"https://doi.org/10.1515/bmc-2021-0005","url":null,"abstract":"<p><p>Weight-related disorders affect more than half of the adult population worldwide; they are also concomitant with a state of chronic low-grade inflammation manifesting in abnormal cytokine production. The present study evaluated the effect of polyphenol and flavonoid extract from <i>Passiflora ligularis</i> (granadilla) on low-grade inflammation and body weight in overweight Wistar rats. To induce weight-gain, rats were fed a chow diet with 30% sucrose water and supplemented with 2.0, 2.5, and 3.0 g/L polyphenol extracts (<i>n</i> = 16). The design was a 3 +1 factorial model performed for 42 days (granadilla polyphenols, 3 levels of supplementation, and 1 control group). In addition to total polyphenol and total flavonoid content, the major identified and quantified polyphenol, via UHPLC, was ferulic acid. Interleukin 6 (IL-6), and cytokine tumor necrosis factor-alpha (TNF-α) were evaluated in serum. A decline in the concentration of TNF-α and in weight-gain was found in <i>P. ligularis</i> (granadilla) groups treated with the 2.5 g/L dose. Consumption of polyphenol extracts from granadilla inhibits interleukin-activity as an indicator of inflammation and aids in body-weight control, considering similar food intake, in overweight Wistar rats.</p>","PeriodicalId":38392,"journal":{"name":"Biomolecular Concepts","volume":" ","pages":"36-45"},"PeriodicalIF":0.0,"publicationDate":"2021-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1515/bmc-2021-0005","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39081707","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":"Everolimus-induced effector mechanism in macrophages and survivability of Erdman, CDC1551 and HN878 strains of <i>Mycobacterium tuberculosis</i> infection.","authors":"Ruoqiong Cao, Kimberly To, Nala Kachour, Abrianna Beever, James Owens, Airani Sathananthan, Pooja Singh, Afsal Kolloli, Selvakumar Subbian, Vishwanath Venketaraman","doi":"10.1515/bmc-2021-0006","DOIUrl":"10.1515/bmc-2021-0006","url":null,"abstract":"<p><p>With a disease as widespread and destructive as tuberculosis, more effective drugs and healthcare strategies, in addition to the current antibiotics regimen, are crucial for the enhanced well-being of millions of people suffering from the disease. Host-directed therapy is a new and emerging concept in treating chronic infectious diseases, such as tuberculosis. Repurposing of anti-cancer drugs, such as everolimus, may be an effective way to supplement the standard antibiotic treatment. Individuals with type 2 diabetes are increasingly susceptible to co-morbidities and co-infections including <i>Mycobacterium tuberculosis,</i> the causative agent of tuberculosis. We demonstrated in this study that <i>in vitro</i> everolimus treatment of granulomas from individuals with type 2 diabetes caused significant reduction in the viability of <i>Mycobacterium tuberculosis.</i>Further investigations revealed the effects of everolimus in targeting foamy macrophages, a macrophage phenotype that forms around granulomas, and is characterized by a higher lipid accumulation inside the cells. These foamy macrophages are thought to harbor dormant bacilli, which are potential sources of disease reactivation. Therefore, blocking foamy macrophage formation would help better killing of intracellular bacteria. Here, we report the potential of everolimus treatment to downregulate lipid content within the foamy macrophages of <i>in vitro</i> granulomas, thus leading to a potential decrease in the number of foamy macrophages and a more robust response to <i>Mycobacterium tuberculosis</i>.</p>","PeriodicalId":38392,"journal":{"name":"Biomolecular Concepts","volume":" ","pages":"46-54"},"PeriodicalIF":0.0,"publicationDate":"2021-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1515/bmc-2021-0006","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39039261","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Myosteatosis in NAFLD patients correlates with plasma Cathepsin D.","authors":"Lingling Ding,&nbsp;Toon J I De Munck,&nbsp;Yvonne Oligschlaeger,&nbsp;Inês Magro Dos Reis,&nbsp;Jef Verbeek,&nbsp;Ger H Koek,&nbsp;Tom Houben,&nbsp;Ronit Shiri-Sverdlov","doi":"10.1515/bmc-2021-0004","DOIUrl":"https://doi.org/10.1515/bmc-2021-0004","url":null,"abstract":"<p><p>Previously, we have shown that hepatic lipid accumulation induces the secretion of cathepsin D (CTSD), and that plasma CTSD levels are associated with increased inflammation and disease severity in nonalcoholic fatty liver disease (NAFLD). Although it is clear that the liver is a major source of plasma CTSD, it is unknown whether other metabolically active organs such as the muscle, also associate with plasma CTSD levels in NAFLD patients. Therefore, the aim of this study was to explore the relation between lipid accumulation in the muscle (myosteatosis) and plasma CTSD levels in forty-five NAFLD patients. We observed that hepatic steatosis positively associated with plasma CTSD levels, confirming the previously established link between plasma CTSD and the liver. Furthermore, a positive association between myosteatosis and plasma CTSD levels was observed, which was independent of sex, age, BMI, waist circumference and hepatic steatosis. By establishing a positive association between myosteatosis and plasma CTSD levels, our findings suggest that, in addition to the liver, the muscle is also linked to plasma CTSD levels in NAFLD patients. The observed link between myosteatosis and plasma CTSD levels supports the concept of a significant role of the skeletal muscle in metabolic disturbances in metabolic syndrome-related disorders.</p>","PeriodicalId":38392,"journal":{"name":"Biomolecular Concepts","volume":" ","pages":"27-35"},"PeriodicalIF":0.0,"publicationDate":"2021-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1515/bmc-2021-0004","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38984937","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 Effects of Oral Liposomal Glutathione and In Vitro Everolimus in Altering the Immune Responses against <i>Mycobacterium bovis</i> BCG Strain in Individuals with Type 2 Diabetes.","authors":"Kimberly To,&nbsp;Ruoqiong Cao,&nbsp;Aram Yegiazaryan,&nbsp;James Owens,&nbsp;Kayvan Sasaninia,&nbsp;Charles Vaughn,&nbsp;Mohkam Singh,&nbsp;Edward Truong,&nbsp;Airani Sathananthan,&nbsp;Vishwanath Venketaraman","doi":"10.1515/bmc-2021-0003","DOIUrl":"https://doi.org/10.1515/bmc-2021-0003","url":null,"abstract":"<p><p>Tuberculosis (TB) caused by <i>Mycobacterium tuberculosis</i> (<i>M. tb</i>) still remains a devastating infectious disease in the world. There has been a daunting increase in the incidence of Type 2 Diabetes Mellitus (T2DM) worldwide. T2DM patients are three times more vulnerable to <i>M. tb</i> infection compared to healthy individuals. TB-T2DM coincidence is a challenge for global health control. Despite some progress in the research, <i>M. tb</i> still has unexplored characteristics in successfully evading host defenses. The lengthy duration of treatment, the emergence of multi-drug-resistant strains and extensive-drug-resistant strains of <i>M. tb</i> have made TB treatment very challenging. Previously, we have tested the antimycobacterial effects of everolimus within <i>in vitro</i> granulomas generated from immune cells derived from peripheral blood of healthy subjects. However, the effectiveness of everolimus treatment against mycobacterial infection in individuals with T2DM is unknown. Furthermore, the effectiveness of the combination of <i>in vivo</i> glutathione (GSH) supplementation in individuals with T2DM along with <i>in vitro</i> treatment of isolated immune cells with everolimus against mycobacterial infection has never been tested. Therefore, we postulated that liposomal glutathione (L-GSH) and everolimus would offer great hope for developing adjunctive therapy for mycobacterial infection. L-GSH or placebo was administered to T2DM individuals orally for three months. Study subjects' blood was drawn pre- and post-L-GSH/or placebo supplementation, where Peripheral Blood Mononuclear Cells (PBMCs) were isolated from whole blood to conduct <i>in vitro</i> studies with everolimus. We found that <i>in vitro</i> treatment with everolimus, an mTOR (membrane target of rapamycin) inhibitor, significantly reduced intracellular <i>M. bovis</i> BCG infection alone and in conjunction with L-GSH supplementation. Furthermore, we found L-GSH supplementation coupled with <i>in vitro</i> everolimus treatment produced a greater effect in inhibiting the growth of intracellular <i>Mycobacterium bovis</i> BCG, than with the everolimus treatment alone. We also demonstrated the functions of L-GSH along with <i>in vitro</i> everolimus treatment in modulating the levels of cytokines such as IFN-γ, TNF-α, and IL-2 and IL-6, in favor of improving control of the mycobacterial infection. In summary, <i>in vitro</i> everolimus-treatment alone and in combination with oral L-GSH supplementation for three months in individuals with T2DM, was able to increase the levels of T-helper type 1 (Th1) cytokines IFN-γ, TNF-α, and IL-2 as well as enhance the abilities of granulomas from individuals with T2DM to improve control of a mycobacterial infection.</p>","PeriodicalId":38392,"journal":{"name":"Biomolecular Concepts","volume":" ","pages":"16-26"},"PeriodicalIF":0.0,"publicationDate":"2021-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1515/bmc-2021-0003","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38963936","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}