scholarly journals Pathophysiology, Clinical Characteristics of Diabetic Cardiomyopathy: Therapeutic Potential of Natural Polyphenols

2020 ◽  
Vol 7 ◽  
Author(s):  
Neha Atale ◽  
Dhananjay Yadav ◽  
Vibha Rani ◽  
Jun-O Jin
Keyword(s):  
Diabetic Cardiomyopathy ◽  
Therapeutic Potential ◽  
Diabetic Patients ◽  
Future Perspectives ◽  
Local Inflammation ◽  
Natural Polyphenols ◽  
Culture Models ◽  
Metabolic Activities ◽  
Cell Culture Models ◽  
Potential Use

Diabetic cardiomyopathy (DCM) is an outcome of disturbances in metabolic activities through oxidative stress, local inflammation, and fibrosis, as well as a prime cause of fatality worldwide. Cardiovascular disorders in diabetic individuals have become a challenge in diagnosis and formulation of treatment prototype. It is necessary to have a better understanding of cellular pathophysiology that reveal the therapeutic targets and prevent the progression of cardiovascular diseases due to hyperglycemia. Critical changes in levels of collagen and integrin have been observed in the extracellular matrix of heart, which was responsible for cardiac remodeling in diabetic patients. This review explored the understanding of the mechanisms of how the phytochemicals provide cardioprotection under diabetes along with the caveats and provide future perspectives on these agents as prototypes for the development of drugs for managing DCM. Thus, here we summarized the effect of various plant extracts and natural polyphenols tested in preclinical and cell culture models of diabetic cardiomyopathy. Further, the potential use of selected polyphenols that improved the therapeutic efficacy against diabetic cardiomyopathy is also illustrated.

scholarly journals Dynamics of Internalization and Intracellular Interaction of Tau Antibodies and Human Pathological Tau Protein in a Human Neuron-Like Model

2020 ◽  
Vol 11 ◽  
Author(s):  
Dov B. Shamir ◽  
Yan Deng ◽  
Qian Wu ◽  
Swananda Modak ◽  
Erin E. Congdon ◽  
...  
Keyword(s):  
Tau Protein ◽  
Therapeutic Potential ◽  
Ex Vivo ◽  
Human Model ◽  
Paired Helical Filament ◽  
Isotype Control ◽  
Culture Models ◽  
Cellular Compartments ◽  
Cell Culture Models

We and others have shown in various in vivo, ex vivo and cell culture models that several tau antibodies interact with pathological tau within neurons. To further clarify this interaction in a dynamic human model, we differentiated SH-SY5Y cells with retinoic acid and BDNF to create a neuron-like model. Therein, tau antibodies were primarily taken up by receptor-mediated endocytosis, and prevented toxicity of human brain-derived paired helical filament-enriched tau (PHF). Subsequently, we monitored in real-time the interaction of antibodies and PHF within endocytic cellular compartments. Cells were pre-treated with fluorescently-tagged PHF and then incubated with tau antibodies, 4E6, 6B2, or non-specific isotype control IgG1 labeled with a pH sensitive dye. The uptake and binding of the efficacious antibody, 4E6, to PHF occurred mainly within the soma, whereas the ineffective antibody, 6B2, and ineffective control IgG1, were visualized via the processes and showed limited colocalization with PHF within this period. In summary, we have developed a neuron-like model that clarifies the early intracellular dynamics of the interaction of tau antibodies with pathological tau, and identifies features associated with efficacy. Since the model is entirely human, it is suitable to verify the therapeutic potential of humanized antibodies prior to extensive clinical trials.

scholarly journals Development of Feline Ileum- and Colon-Derived Organoids and Their Potential Use to Support Feline Coronavirus Infection

Cells ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 2085 ◽  
Author(s):  
Gergely Tekes ◽  
Rosina Ehmann ◽  
Steeve Boulant ◽  
Megan L. Stanifer
Keyword(s):  
Cell Culture ◽  
Molecular Mechanisms ◽  
Domestic Cat ◽  
Contributing Factors ◽  
Feline Infectious Peritonitis ◽  
Culture Models ◽  
Coronavirus Infection ◽  
Cell Culture Models ◽  
Feline Coronavirus ◽  
Potential Use

Feline coronaviruses (FCoVs) infect both wild and domestic cat populations world-wide. FCoVs present as two main biotypes: the mild feline enteric coronavirus (FECV) and the fatal feline infectious peritonitis virus (FIPV). FIPV develops through mutations from FECV during a persistence infection. So far, the molecular mechanism of FECV-persistence and contributing factors for FIPV development may not be studied, since field FECV isolates do not grow in available cell culture models. In this work, we aimed at establishing feline ileum and colon organoids that allow the propagation of field FECVs. We have determined the best methods to isolate, culture and passage feline ileum and colon organoids. Importantly, we have demonstrated using GFP-expressing recombinant field FECV that colon organoids are able to support infection of FECV, which were unable to infect traditional feline cell culture models. These organoids in combination with recombinant FECVs can now open the door to unravel the molecular mechanisms by which FECV can persist in the gut for a longer period of time and how transition to FIPV is achieved.

scholarly journals The Potential Role of Flavonoids in Ameliorating Diabetic Cardiomyopathy via Alleviation of Cardiac Oxidative Stress, Inflammation and Apoptosis

2021 ◽  
Vol 22 (10) ◽  
pp. 5094
Author(s):  
Fatin Farhana Jubaidi ◽  
Satirah Zainalabidin ◽  
Izatus Shima Taib ◽  
Zariyantey Abd Hamid ◽  
Siti Balkis Budin
Keyword(s):  
Oxidative Stress ◽  
Risk Factors ◽  
Diabetic Cardiomyopathy ◽  
Mortality Risk ◽  
Potential Role ◽  
Therapeutic Potential ◽  
Biological Activities ◽  
Diabetic Patients ◽  
Remedial Actions

Diabetic cardiomyopathy is one of the major mortality risk factors among diabetic patients worldwide. It has been established that most of the cardiac structural and functional alterations in the diabetic cardiomyopathy condition resulted from the hyperglycemia-induced persistent oxidative stress in the heart, resulting in the maladaptive responses of inflammation and apoptosis. Flavonoids, the most abundant phytochemical in plants, have been reported to exhibit diverse therapeutic potential in medicine and other biological activities. Flavonoids have been widely studied for their effects in protecting the heart against diabetes-induced cardiomyopathy. The potential of flavonoids in alleviating diabetic cardiomyopathy is mainly related with their remedial actions as anti-hyperglycemic, antioxidant, anti-inflammatory, and anti-apoptotic agents. In this review, we summarize the latest findings of flavonoid treatments on diabetic cardiomyopathy as well as elucidating the mechanisms involved.

scholarly journals Adeno-associated viral (AAV) vector-mediated therapeutics for diabetic cardiomyopathy – current and future perspectives

2021 ◽  
Vol 135 (11) ◽  
pp. 1369-1387
Author(s):  
Darnel Prakoso ◽  
Mitchel Tate ◽  
Miles J. De Blasio ◽  
Rebecca H. Ritchie
Keyword(s):  
Heart Failure ◽  
Gene Therapy ◽  
Diabetic Cardiomyopathy ◽  
Viral Vector ◽  
Therapeutic Potential ◽  
Future Perspectives ◽  
Cardiac Damage ◽  
Pharmacological Agents ◽  
Potential Alternative ◽  
Artery Disease

Abstract Diabetes increases the prevalence of heart failure by 6–8-fold, independent of other comorbidities such as hypertension and coronary artery disease, a phenomenon termed diabetic cardiomyopathy. Several key signalling pathways have been identified that drive the pathological changes associated with diabetes-induced heart failure. This has led to the development of multiple pharmacological agents that are currently available for clinical use. While fairly effective at delaying disease progression, these treatments do not reverse the cardiac damage associated with diabetes. One potential alternative avenue for targeting diabetes-induced heart failure is the use of adeno-associated viral vector (AAV) gene therapy, which has shown great versatility in a multitude of disease settings. AAV gene therapy has the potential to target specific cells or tissues, has a low host immune response and has the possibility to represent a lifelong cure, not possible with current conventional pharmacotherapies. In this review, we will assess the therapeutic potential of AAV gene therapy as a treatment for diabetic cardiomyopathy.

scholarly journals Haemophilin-Producing Strains of Haemophilus haemolyticus Protect Respiratory Epithelia from NTHi Colonisation and Internalisation

Pathogens ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 29
Author(s):  
Brianna Atto ◽  
Dale Kunde ◽  
David A Gell ◽  
Stephen Tristram
Keyword(s):  
Inhibitory Activity ◽  
Therapeutic Potential ◽  
Epithelial Cell Line ◽  
The Novel ◽  
Nontypeable Haemophilus Influenzae ◽  
Respiratory Epithelia ◽  
Culture Models ◽  
Host Cell Interactions ◽  
Cell Culture Models

Nontypeable Haemophilus influenzae (NTHi) is a significant respiratory tract pathogen responsible for infections that collectively pose a substantial health and socioeconomic burden. The clinical course of these infections is largely dictated by NTHi interactions with host respiratory epithelia, and thus, approaches that disrupt colonisation and invasion may have significant therapeutic potential. Survival, successful host–cell interactions, and pathogenesis are reliant on NTHi’s ability to sequester host-derived haem. Previously, we demonstrated the therapeutic potential of exploiting this haem-dependence using a closely related competitor bacterium, Haemophilus haemolyticus (Hh). Hh strains capable of producing the novel haem-binding protein haemophilin (Hpl) possessed potent inhibitory activity by restricting NTHi access to haem in a broth co-culture environment. Here, we extend this work to cell culture models that more closely represent the human respiratory epithelium and show that Hh strains with high levels of hpl expression protect epithelial cell line monolayers against adhesion and invasion by NTHi. Inhibitory activity was dependent on the level of Hpl production, which was stimulated by NTHi challenge and nasopharyngeal cell exposure. Provided these protective benefits translate to in vivo applications, Hpl-producing Hh may have probiotic utility against NTHi infections by inhibiting requisite nasopharyngeal colonisation.

scholarly journals Dihydromyricetin Protects against Diabetic Cardiomyopathy in Streptozotocin-Induced Diabetic Mice

2017 ◽  
Vol 2017 ◽  
pp. 1-13 ◽  
Author(s):  
Bin Wu ◽  
Jie Lin ◽  
Jian Luo ◽  
Dong Han ◽  
Miaomiao Fan ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cardiac Function ◽  
Diabetic Cardiomyopathy ◽  
Structural Changes ◽  
Therapeutic Potential ◽  
Control Group ◽  
Diabetic Patients ◽  
Distilled Water ◽  
Diabetic Mice ◽  
Diabetes Group

Diabetic cardiomyopathy (DCM) is an important cause of heart failure in diabetic patients. The present study sought to explore the potential effects of dihydromyricetin (DHM) on DCM and its possible mechanism. A diabetic model was induced by intraperitoneal injection of streptozotocin (STZ) in C57BL/6J mice. Two weeks after the STZ injection, mice were randomly allocated into the following 4 groups for treatment: the control group (CON), the control treated with DHM group (CON + DHM), the diabetes group (DM), and the diabetes treated with DHM group (DM + DHM). DHM was dissolved in distilled water and administered daily by gavage. For 14 weeks, the CON + DHM group and DM + DHM group were given a dose of 100 mg/kg/day DHM (Sigma-Aldrich), while the CON and DM groups were intragastrically given equivalent volumes of distilled water. Assessments and comparisons were made among the groups based on cardiac function and structural changes, inflammation factors, markers of oxidative stress, mitochondria function, apoptosis, and autophagy. The DHM treatment normalized body weight, preserved cardiac function, attenuated oxidative stress (MDA, SOD, and GSH-Px), reduced the levels of inflammation factors (IL-6, TNF-α), alleviated pathological changes, improved mitochondrial function (ATP content, CS activity, and complex Ι/ΙΙ/ΙΙΙ/ΙV/V activities), inhibited cardiac apoptosis, and restored autophagy in diabetic mice. DHM may have a great therapeutic potential in the treatment of DCM.

Integrating Bioinformatics Strategies in Cancer Immunotherapy: Current and Future Perspectives

2020 ◽  
Vol 23 (8) ◽  
pp. 687-698 ◽  
Author(s):  
Houda N. Washah ◽  
Elliasu Y. Salifu ◽  
Opeyemi Soremekun ◽  
Ahmed A. Elrashedy ◽  
Geraldene Munsamy ◽  
...  
Keyword(s):  
Cancer Immunotherapy ◽  
Therapeutic Potential ◽  
Cell Cancer ◽  
Full Potential ◽  
Future Perspectives ◽  
The Past ◽  
Bioinformatics Tools ◽  
Treatment Paradigm ◽  
Immunotherapy Of Cancer ◽  
Significant Attention

For the past few decades, the mechanisms of immune responses to cancer have been exploited extensively and significant attention has been given into utilizing the therapeutic potential of the immune system. Cancer immunotherapy has been established as a promising innovative treatment for many forms of cancer. Immunotherapy has gained its prominence through various strategies, including cancer vaccines, monoclonal antibodies (mAbs), adoptive T cell cancer therapy, and immune checkpoint therapy. However, the full potential of cancer immunotherapy is yet to be attained. Recent studies have identified the use of bioinformatics tools as a viable option to help transform the treatment paradigm of several tumors by providing a therapeutically efficient method of cataloging, predicting and selecting immunotherapeutic targets, which are known bottlenecks in the application of immunotherapy. Herein, we gave an insightful overview of the types of immunotherapy techniques used currently, their mechanisms of action, and discussed some bioinformatics tools and databases applied in the immunotherapy of cancer. This review also provides some future perspectives in the use of bioinformatics tools for immunotherapy.

scholarly journals Factors to consider when interrogating 3D culture models with plate readers or automated microscopes

2021 ◽  
Author(s):  
Terry Riss ◽  
O. Joseph Trask
Keyword(s):  
Cell Culture ◽  
Three Dimensional ◽  
3D Culture ◽  
Fluorescent Imaging ◽  
Culture Models ◽  
Assay Methods ◽  
Diffusion Rates ◽  
Cell Culture Models ◽  
Dimensional Cell ◽  
Cells Cultured

AbstractAlong with the increased use of more physiologically relevant three-dimensional cell culture models comes the responsibility of researchers to validate new assay methods that measure events in structures that are physically larger and more complex compared to monolayers of cells. It should not be assumed that assays designed using monolayers of cells will work for cells cultured as larger three-dimensional masses. The size and barriers for penetration of molecules through the layers of cells result in a different microenvironment for the cells in the outer layer compared to the center of three-dimensional structures. Diffusion rates for nutrients and oxygen may limit metabolic activity which is often measured as a marker for cell viability. For assays that lyse cells, the penetration of reagents to achieve uniform cell lysis must be considered. For live cell fluorescent imaging assays, the diffusion of fluorescent probes and penetration of photons of light for probe excitation and fluorescent emission must be considered. This review will provide an overview of factors to consider when implementing assays to interrogate three dimensional cell culture models.

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