Volume Articles

Commentary: Effects of different lipoprotein apheresis methods on serum protein levels

Ulrich Julius^1*

¹Lipidology and Center for Extracorporeal Treatment, Department of Internal Medicine III, University Hospital Carl Gustav Carus at the Technische Universität Dresden, Germany Fetscherstr. 74, 01307 Dresden (Germany)

Expansion of Gamma Delta T Cells - A Short Review on Bisphosphonate and K562-Based Methods

Wee Kiat Tan¹, Johan CK Tay², Jieming Zeng³, Min Zheng⁴, Shu Wang^2,3*

¹Tessa Therapeutics, Pte Ltd., Singapore 239351

²Department of Biological Sciences, National University of Singapore, Singapore 117543

³Institute of Bioengineering and Nanotechnology, Singapore 138669

⁴Department of Dermatology, Second Affiliated Hospital, Zhejiang University, School of Medicine, China 310009

Faeco-orally transmitted viral hepatitis in african children

Emmanuel E. Ekanem^1*, Joanan M. Ikobah¹, Henry C. Okpara²

¹DEPARTMENT OF PAEDIATRICS, UNIVERSITY OF CALABAR AND UNIVERSITY OF CALABAR TEACHING HOSPITAL, CALABAR, NIGERIA.

²DEPARTMENT OF CHEMICAL PATHOLOGY, UNIVERSITY OF CALABAR AND UNIVERSITY OF CALABAR TEACHING HOSPITAL, NIGERIA.

The faeco-orally transmitted hepatotropic viruses – hepatitis A and hepatitis E viruses- are endemic in Africa. While transmission has reduced remarkbly in Europe and North America in the past decades, it has remained unchanged in Africa with hepatitis A prevalence remaining at above 50% and hepatitis E more than 7%. Much of this transmission occurs during childhood with the important drivers/predictors being poor water supply, poor sewage disposal facilities, low socioeconomic class, crowding, and poor social conditions arising from conflict. Initial clinical features in children are difficult to distinguish from malaria which is also endemic in the region. Commercially available ELISA kits present the best option for laboratory diagnosis of both viruses in Africa. While effective vaccines suitable for the African situation have been developed recently, improved water supply and sanitation are sine qua non for the prevention of transmission of both viruses among African children. Interventional studies are needed in the region.

MUC1 and carbohydrate associated antigens in head and neck squamous cell carcinoma: our experience

María Virginia Croce¹*, Martín E. Rabassa¹, Amada Segal-Eiras¹

¹Centre of Basic and Applied Immunological Research (CINIBA), Faculty of Medical Sciences, National University of La Plata, Argentina.

Cyclin D1 and P27KIP1: The Gatekeepers of Dysplasia

Mahmoud M. Bakr¹, Simon Guan², Norman Firth³, Robert M. Love^1*

¹School of Dentistry and Oral Health, Griffith University, Australia

²School of Dentistry, University of Otago, New Zealand

³University of Queensland, Brisbane, Australia

There is increasing evidence suggesting that cyclins, cyclin-dependent kinases (CDKs), and cyclin-dependent kinase inhibitors (CDIs) either are themselves targets for genetic change in cancer or are disrupted secondarily by other oncogenic events. Cyclin D1 and p27^KIP1 are two important regulators at the G1/S checkpoint. Cyclin D1 is an oncogene of cell cycle regulation with positive effect. Normally, cyclin D1 at G1 is constant or at a very low level and its excessive expression may be associated with the disordered proliferation of cells leading to malignant change. On the other hand, p27^KIP1 is an anti-oncogene for cell cycle regulation, which functions as a negative regulator. Under the regulation of TGF-β, p27^KIP1 inhibits the activity of oncogenes and controls the transition of the G1/S phase mainly by the interaction with CDK and CDK-Cyclin in order to inhibit cell proliferation and give cells opportunities to repair DNA. In addition, p27^KIP1 not only acts as CDK inhibitor, but also promotes cell differentiation and induces the apoptosis of cells. In this article we review studies that have explored the effects of cyclin D1 and P27^KIP1 on cancer progression and dysplasia with a specific focus on oral dysplasia and oral squamous cell carcinoma (OSCC). We also aim to shed some light on the different means of evaluating the interaction between Cyclin D1 and P27^KIP1 as well as the immunohistochemical reactions associated with different forms of cyclin D1.

LOX-1-deficient mice are resistant to zymosan-induced arthritis: A mini review

Kazuhiko Hashimoto^1*, Yutaka Oda¹, Kotaro Yamagishi¹, Ichiro Tsukamoto¹, Masao Akagi¹

¹Department of Orthopedic Surgery, Kindai University Hospital, Osaka-Sayama City, Osaka 589-8511, Japan

Background: Some reports have shown that metabolic syndrome, including hypertension, hyperlipidemia, and diabetes mellitus, contributes to osteoarthritis (OA) development. Further, lectin-like oxidized low-density lipoprotein (ox-LDL) and ox-LDL receptor-1 (LOX-1), which contributes to atherosclerosis, have also been considered factors contributing to OA development. Several studies have suggested that the LOX-1/ox-LDL system is involved in OA development in vitro. We have suggested the same and conducted in vitro and in vivo studies to validate this concept. However, the role of the LOX-1/ox-LDL system in OA development has not been clarified. This study aimed to identify the mechanism of the LOX-1/ox-LDL system to clarify OA development.

Methods: A zymosan-induced arthritis model was used to identify the mechanism of the LOX-1/ox-LDL system using LOX-1-knockout (KO) mice. Zymosan was administered via the intra-articular route to induce arthritis.

Results: From our experiment, we found that the LOX-1/ox-LDL system contributes to OA development through matrix metalloproteinase-3.

Conclusion: Our findings suggest that the treatment of abnormal lipid metabolism may contribute to the prevention and suppression of arthritis.

Post-cardiac injury syndrome in the Emergency Department: mini-review

Antonio Voza^1*

¹Emergency Department, Humanitas Research Hospital, Via Manzoni 56, 20089 Rozzano, Italy

The term post-cardiac injury syndrome (PCIS) defines a group of inflammatory diseases involving predominantly the pericardium. The syndrome results from a cardiac injury and refers mainly to post-myocardial infarction pericarditis, post-pericardiotomy syndrome and post-traumatic pericarditis (including iatrogenic conditions appearing after percutaneous interventions).

Signs and symptoms are similar to those seen in acute pericarditis and pericardial effusion in other clinical settings. The diagnosis is clinical and could be challenging in the Emergency Department (ED). PCIS should be considered as an alternative diagnosis to acute pericarditis in case of unilateral right-sided, massive, or transudative pleural effusion.

Although typically a benign condition, PCIS may result in significant morbidity and potential mortality; tamponade and constrictive pericarditis represent the leading complications. Therefore, early detection is clinically relevant. Currently, a combination of nonsteroidal anti-inflammatory drugs and colchicine is the mainstay treatment for this condition. Colchicine has also appeared to be effective in primary prevention of PCIS after cardiac surgery.

The purpose of this article is to review the principle clinical characteristics of PCIS in order to achieve an early diagnosis.

Clinical implications of Epstein-Barr virus strain diversity

Ana Cirac^1,2,3, Uta Behrends^1,2,3, and Josef Mautner^1,2,3*

¹Children’s Hospital, Technische Universität München, Munich, Germany

²Research Unit Gene Vectors, Helmholtz Zentrum München, Munich, Germany

²German Centre for Infection Research (DZIF), partner site Munich, Germany

The Epstein-Barr virus (EBV), a ubiquitous γ-herpesvirus, has been implicated in the etiology of several acute and chronic inflammatory, autoimmune, and malignant diseases. Although considered a genetically stable virus, recent sequence information obtained from a large number of viral isolates from around the world revealed that numerous viral variants exist. Whether these different strains differ in pathogenicity and immunogenicity and thereby contribute to the varying incidence rates of several EBV-associated diseases in different geographical regions is now studied intensively. The recent identification of amino acid sequence polymorphisms in a high percentage of all known virus-specific CD4+ and CD8+ T-cell epitopes, and of holes in the individual T-cell repertoire against epitopes derived from strain variants, may suggest that antiviral immunity is incompletely cross-protective against diverse EBV strains. These findings may have implications for immunological approaches seeking to prevent, monitor, or treat EBV-associated diseases.

Phagocytosis alteration preceding staphylococcal infection

Wilma Carvalho Neves Forte¹*, Tainá Mosca¹

¹Immunology Discipline, Santa Casa de Sao Paulo School of Medical Sciences, São Paulo, SP, Brazil

Implications of the HDAC6-ERK1 feed forward loop in immunotherapy

Jheng-Yu Wu^{1, 2}, Niko Moses^1,2, Wenlong Bai³, Xiaohong Mary Zhang^1,2*

¹Department of Oncology, Molecular Therapeutics Program, Karmanos Cancer Institute, Detroit, Michigan 48201

²Wayne State University School of Medicine, Detroit, Michigan 48201

³Department of Pathology and Cell Biology, Morsani College of Medicine, University of South Florida, Tampa, FL 33612

The oncogene HDAC6 controls numerous cell processes that are related to tumorigenesis and metastasis, and has recently arisen as a target to treat malignancies. The ERK cascade is a classic pathway driving oncogenesis, and the components of this pathway are either highly mutated in cancers or are vital in cancer’s pathological activity. The interactions between these important components of tumor proliferation have been examined, and our research has demonstrated that they regulate each other as evidenced by different posttranslational modifications. Preclinical evidence also supports clinical trials cotargeting these two pathways, which may provide better efficacy than single treatment. Furthermore, HDAC6 and ERK both participate in the regulation of T cell maturation and may have implications on the functions of immune cells. This leads to the possibility of connecting HDAC6 and ERK to immunotherapy. In this review, we summarize the published studies about the interaction of HDAC6 and ERK cascade and their relationship to cancers. We also include the association of HDAC6 and ERK to immune system and discuss the plausibility of linking these to immunotherapy.

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

Manuel Freire^1*, 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.

Protein Kinase C-epsilon in Membrane Delivery during Phagocytosis

Anna E. D’Amico¹ and Michelle R. Lennartz^1*

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.

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

Danielson H^1*, 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

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

Shiyu Dai¹, Hualin Wang¹, Fei Deng^1*

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.

Myeloid-derived suppressor cells and their "inconvenient" plasticity

David Escors^1,2, Grazyna Kochan^1*

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.

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

S.R. Mishra¹, Mihir Sarkar^2*

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.