Vol 2-2 Commentary

Commentary: The Starving Brain: Overfed meets undernourished in the pathology of mild cognitive impairment (MCI) and Alzheimer's disease (AD)

Kelly Gibas1*

1Department of Human Kinetics and Applied Health Science, 3900 Bethel Drive, Bethel University, MN, USA

The emerging bioenergetic model for cognitive decline defines late-onset, neural impairment as symptomatic of brain starvation resulting from the physiological paradox of chronic cerebral hyperinsulinemia/hyperglycemia concurrent with episodic hypoglycemia. The catabolic injury to the brain occur linear to energy deficits and mirror the progression of peripheral, cellular insulin resistance and type II diabetes; this pathology of brain starvation is being recognized as Type III diabetes. An energetic construct of neurodegeneration centers on homeostatic energy failure, as hypothesized by Demetrius and Simon (2012)1; the model focuses on the centralized role of astrocytes for the metabolic coupling of lactate to feed hungry neurons. Healthy fed/fasted signaling within the cells of the brain involves coordinated action of astrocytes and neurons. The astrocytes’ primary mode of energy production, via brain-side, glucose transporter 1 (GLUT1), is glycolysis; glucose is metabolized anaerobically to lactate. Lactate is released by the astrocyte into the extracellular milieu and utilized as supplemental energy for neurons2 (Pellerin, 2007). A recent study, “PSEN1 Mutant iPSC-Derived Model Reveals Severe Astrocyte Pathology in Alzheimer’s Disease,” published in Stem Cell Reports (2017)3 by a team from the University of Eastern Finland confirmed the role of astrocytes as lactate shuttles3. This study was the first to use human stem cells to demonstrate that in patients with AD astrocytes manifest pathological metabolic shifts. Conclusions of the study show astrocytes play a significant role in the early stages of the disease and contribute to metabolic changes in neurons leading to neurodegenerative pathology.

DOI: 10.29245/2578-3009/2018/2.1124 View / Download Pdf View Full Text
Vol 2-2 Mini Review

Drug interactions of monoclonal antibodies-clinical perspective

José M. Serra López-Matencio1, Concepción Martínez Nieto1, Alberto Morell Baladrón1, Santos Castañeda2*

1Hospital Pharmacy Service, Hospital de la Princesa, IIS-Princesa, c / Diego de León 62; 28006-Madrid, Spain

2Rheumatology Service, Hospital de la Princesa, IIS-Princesa, c / Diego de León 62; 28006-Madrid, Spain

Biological agents are used to treat a variety of diseases in many therapeutic areas, including oncology, hematology, rheumatology, gastroenterology, dermatology, neurology, respiratory diseases, hormone deficiency and infections. Since biologics constitute many of the recently approved new therapies, clinical research of drug-drug interactions with biologics has been discussed. Here, we present a personal view of drug-drug interactions with monoclonal antibodies, a predominant class of therapeutic biologics. In this line, we think that the interactions of biological agents with other chemical drugs represent an important issue, completely unknown and with potentially prominent clinical implications, that will have to be taken into account in coming years.

DOI: 10.29245/2578-3009/2018/2.1126 View / Download Pdf View Full Text
Vol 2-2 Mini Review

Development, maintenance and functions of CD8+ T-regulatory cells: Molecular orchestration of FOXP3 transcription

Sreeparna Chakraborty1 & Gaurisankar Sa1*

1Division of Molecular Medicine, Bose Institute, P-1/12, Calcutta Improvement Trust Scheme VII M, Kolkata 700054, India

Modulation of immune cells to rejuvenate the immune responses against cancer becomes a promising strategy for cancer therapy. T-regulatory cells are one of the major hurdles in successful cancer immunotherapy. Recent studies discovered that apart from CD4+ Treg cells, CD8+ Tregs also play roles in tumor immune evasion. Moreover, CD8+ Tregs shows synergistic immunosuppression with CD4+ Treg cells in tumor microenvironment. Several phenotypic markers have been described for peripherally induced CD8+ Treg cells, but till now no universal phenotypic signature has yet established. FOXP3 is the master regulator of Treg cells and its transcription is critically regulated by promoter region as well as three intronic conserved non-coding regions, viz; CNS 1, 2 and 3. In this review, we have described the transcriptional networking associated with the regulation of FOXP3 in tumor-CD8+ Treg cells along with CD4+ nTreg and iTreg cells. Intervention of the intensive transcriptional machinery of FOXP3 regulation may aid to target Treg cells and thus could potentiate immunotherapy of cancer.

DOI: 10.29245/2578-3009/2018/2.1117 View / Download Pdf View Full Text
Vol 2-2 Mini Review

Intestinal bacterial biofilms modulate mucosal immune responses

Melissa Ellermann1 and R. Balfour Sartor2, 3, 4*

1Department of Microbiology, University of Texas Southwestern Medical Center, Dallas, TX, USA.

2Departments of Medicine, University of North Carolina, Chapel Hill, NC, USA.

3Microbiology and Immunology, University of North Carolina, Chapel Hill, NC, USA.

4Center for Gastrointestinal Biology and Disease, University of North Carolina, Chapel Hill, NC, USA.

Host-associated microbial communities modulate numerous aspects of host physiology at the epithelial interface within mucosal environments. Perturbations to this symbiotic relationship between host and microbiota has been linked to numerous microbial-driven pathological states, including Crohn’s disease (CD). This is in part driven by the outgrowth of aggressive resident bacterial strains such as adherent and invasive Escherichia coli (AIEC) and changes in bacterial physiology and function that promote enhanced mucosal association of pathobionts and aberrant stimulation of mucosal immunity. Endogenous bacteria from host-associated microbial communities can adopt a sessile lifestyle and form multicellular structures known as biofilms that are generated through the expression of extracellular adhesion factors that include curli amyloid fibrils, cellulose and type 1 pili. In addition to enabling bacterial attachment to mucosal surfaces, biofilm components also stimulate immune responses and can therefore instigate or perpetuate microbial-driven inflammatory diseases such as CD. These host-bacterial interactions provide pharmacological targets that can potentially be exploited to limit mucosal adherence of aggressive enteric bacteria, inappropriate stimulation of inflammatory immune responses and consequent development of chronic intestinal inflammation.

DOI: 10.29245/2578-3009/2018/2.1122 View / Download Pdf View Full Text
Vol 2-2 Mini Review

Prothymosin α, a protein implicated in the proliferation and survival of lymphocytes

Manuel Freire1*, Pablo Barbeito1, Concepción S. Sarandeses1, Cristina Díaz-Jullien1, Juan Muras1, Guillermo Covelo1, David Moreira1 and Carmen Freire-Cobo1

1The Department of Biochemistry and Molecular Biology, CIBUS, Faculty of Biology, University of Santiago de Compostela, 15782 Santiago de Compostela, Spain

Prothymosin α (ProTα) is a 109-11 amino acid protein widely distributed in mammalian tissues and particularly abundant in lymphoid cells. Genomic and proteomic studies led to consider ProTα as a multifunctional protein implicated in nuclear and cytoplasmic functions. The nuclear function of ProTα is related to chromatin activity through its interaction with core histones and proteins involved in chromatin remodelling, whereas, processes related to the phosphorylation, the proteolytic processing to generate Thymosin α1, and the role as anti-apoptotic factor of ProTα, are linked to its cytoplasmic location. Affinity chromatography and co-immunoprecipitation experiments have demonstrated novel interactions of ProTα with acidic proteins such as SET, ANP32A, and ANP32B in the cytoplasm of proliferating lymphocytes. The stabilization of these interactions by chemical cross-linking with formaldehyde shows that they are formed through associations in six acidic complexes which correspond to selective interactions of SET and ANP32 proteins with ProTα. These ProTα-complexes also include cytoplasmic proteins implicated in membrane remodelling and in mitochondrial activity. In conclusion, these novel protein interactions of ProTα observed in proliferation activity and apoptosis studies, suggest that they might be related to mechanisms involved in the proliferation activity and the apoptotic control of lymphocytes.

DOI: 10.29245/2578-3009/2018/2.1130 View / Download Pdf View Full Text
Vol 2-2 Mini Review

Protein Kinase C-epsilon in Membrane Delivery during Phagocytosis

Anna E. D’Amico1 and Michelle R. Lennartz1*

1Department of Regenerative and Cancer Cell Biology, Albany Medical College, 47 New Scotland Avenue Albany, NY 12208, USA

During phagocytosis, internal membranes are recruited to the site of pathogen binding and fuse with the plasma membrane, providing the membrane needed for pseudopod extension and target uptake. The mechanism by which vesicles destined for the phagosome are generated, targeted, and fuse is unknown. We established that Golgi-associated protein kinase C-epsilon (PKC-ε) is necessary for the addition of membrane during FcγR -mediated phagocytosis. PKC-ε is tethered to the Golgi through interactions between its’ regulatory domain and the Golgi lipids PI4P and diacylglycerol; disruption of these interactions prevents PKC-ε concentration at phagosomes and decreases phagocytosis. The accumulated evidence suggests that PKC-ε orchestrates vesicle formation at the Golgi by a mechanism requiring lipid binding but not enzymatic activity. This review discusses how PKC-ε might mediate vesicle formation at the level of budding and fission. Specifically, we discuss PKC-ε binding partners, the formation of lipid subdomains to generate membrane curvature, and PKC-ε mediated links to the actin and microtubule cytoskeleton to provide tension for vesicle fission. Assimilating information from several model systems, we propose a model for PKC-ε mediated vesicle formation for exocytosis during phagocytosis that may be applicable to other processes that require directed membrane delivery and fusion.

DOI: 10.29245/2578-3009/2018/2.1134 View / Download Pdf View Full Text
Vol 2-2 Commentary

Commentary: Total joint replacement in inhibitor-positive haemophilia: Long-term outcome analysis in fifteen cases

Danielson H1*, Ylinen P1, Yrjönen T1, Lassila R2

1Orton Orthopaedic Hospital, Invalid Foundation, Helsinki, Finland

2Helsinki University and Coagulation Disorders unit, Department of Haematology and Comprehensive Cancer Centre, Helsinki University Hospital, Helsinki, Finland

DOI: 10.29245/2578-3009/2018/2.1129 View / Download Pdf View Full Text
Vol 2-2 Mini Review

Advances and challenges in enveloped virus-like particle (VLP)-based vaccines

Shiyu Dai1, Hualin Wang1, Fei Deng1*

1State Key laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, 430071, China

Virus-like particles (VLPs) are highly organized particles that self-assemble from viral structural proteins. Like parental viruses, VLPs can be either non-enveloped or enveloped and can be produced in different expression systems depending on their complexity. Over the last three decades, VLPs have developed as a high-priority alternative to traditional vaccines against infectious pathogens due to their safety, simplicity and favorable immunological characteristics to induce both humoral and cellular immune responses. Most of emerging and re-emerging viruses that pose a continuous threat to human health are enveloped, but few vaccines are currently available. Advances in expression technology for complex, enveloped VLPs provide new possibilities to develop potent vaccines against pathogenic enveloped viruses. This review describes major progress and challenges in the production of enveloped VLPs, with respect to the main principles in the assembly and budding process, factors that need to be taken into account for the design strategies and choice of relevant production platforms.

DOI: 10.29245/2578-3009/2018/2.1118 View / Download Pdf View Full Text
Vol 2-2 Mini Review

Myeloid-derived suppressor cells and their "inconvenient" plasticity

David Escors1,2, Grazyna Kochan1*

1Navarrabiomed-Fundación Miguel Servet. Complejo Hospitalario de Navarra. Irunlarrea 3, 31008, Pamplona. Navarra. Spain.

2Division of Infection and Immunity. University College London, 5 University Street, WC1E 6JF London, United Kingdom.

Myeloid-derived suppressor cells (MDSCs) comprise certain types of myeloid subsets with strong immunosuppressive activities, which expand at high levels in pathological conditions such as cancer. A major drawback in the study of MDSCs is the extraordinary plasticity of the myeloid lineage that hampers the identification of MDSC subsets, especially in humans. Here we provide a brief overview on MDSCs, their differentiation and the current difficulties in classifying these immunosuppressive subsets.

DOI: 10.29245/2578-3009/2018/2.1135 View / Download Pdf View Full Text
Vol 2-2 Mini Review

Interferon Stimulated Genes (Isgs): Novel Pregnancy Specific Biomarker In Buffaloes (Bubalus bubalis)

S.R. Mishra1, Mihir Sarkar2*

1Department of Veterinary Physiology, College of Veterinary Science and Animal Husbandry, OUAT, Bhubabeswar, Odisha, 751003, India

2Physiology & Climatology Division, Indian Veterinary Research Institute, Izatnagar, Uttar Pradesh, 243122, India

Early embryonic mortality (EEM) has been shown to be the prime cause of pregnancy failure in domestic species incurring severe economic losses in terms of milk production in dairy cows in most of the tropical countries including India. Despite of the availability of various diagnosis methods for the pregnancy detection the domestic animals are still prone to reproductive failure before the onset of implantation. Recently, a group of genes called as interferon stimulated genes (ISG) have been shown to be expressed during peri-implanation period which could serve as a potential diagnostic marker for early detection of pregnancy in domestic species. The present mini review highlights the differential expression dynamics of interferon stimulated genes (ISG) during early pregnancy period in buffalo.

DOI: 10.29245/2578-3009/2018/2.1132 View / Download Pdf View Full Text