Carcinoma of the stomach is one of the most prevalent cancer types in the world. Although the incidence of gastric cancer is declining, the outcomes of gastric cancer patients remain dismal because of the lack of effective biomarkers to detect early gastric cancer. Modern biomedical research has explored many potential gastric cancer biomarker genes by utilising serum protein antigens, oncogenic genes or gene families through improving molecular biological technologies, such as microarray, RNA-Seq and the like. Recently, the small noncoding microRNAs (miRNAs) have been suggested to be critical regulators in the oncogenesis pathways and to serve as useful clinical biomarkers. This new class of biomarkers is emerging as a novel molecule for cancer diagnosis and prognosis, including gastric cancer. By translational suppression of target genes, miRNAs play a significant role in the gastric cancer cell physiology and tumour progression. There are potential implications of previously discovered gastric cancer molecular biomarkers and their expression modulations by respective miRNAs. Therefore, many miRNAs are found to play oncogenic roles or tumour-suppressing functions in human cancers. With the surprising stability of miRNAs in tissues, serum or other body fluids, miRNAs have emerged as a new type of cancer biomarker with immeasurable clinical potential.

Reverse genetics systems allow artificial generation of non-segmented and segmented negative-sense RNA viruses, like influenza viruses, entirely from cloned cDNA. Since the introduction of reverse genetics systems over a decade ago, the ability to generate ‘designer’ influenza viruses in the laboratory has advanced both basic and applied research, providing a powerful tool to investigate and characterise host–pathogen interactions and advance the development of novel therapeutic strategies. The list of applications for reverse genetics has expanded vastly in recent years. In this review, we discuss the development and implications of this technique, including the recent controversy surrounding the generation of a transmissible H5N1 influenza virus. We will focus on research involving the identification of viral protein function, development of live-attenuated influenza virus vaccines, host–pathogen interactions, immunity and the generation of recombinant influenza virus vaccine vectors for the prevention and treatment of infectious diseases and cancer.

Experimental and human studies have shown that proteinuria contributes to the progression of renal disease. Overexposure to filtered proteins promotes the expression and release of chemokines by tubular epithelial cells, thus leading to inflammatory cell recruitment and renal impairment. This review focuses on recent progress in cellular and molecular understanding of the role of chemokines in the pathogenesis of proteinuria-induced renal injury, as well as their clinical implications and therapeutic potential.

Autoimmune disease manifests in numerous forms, but as a disease group is relatively common in the population. It is complex in aetiology, with genetic and environmental determinants. The involvement of gene variants in autoimmune disease is well established, and evidence for significant involvement of the environment in various disease forms is growing. These factors may act independently, or they may interact, with the effect of one factor influenced by the presence of another. Identifying combinations of genetic and environmental factors that interact in autoimmune disease has the capacity to more fully explain disease risk profile, and to uncover underlying molecular mechanisms contributing to disease pathogenesis. In turn, such knowledge is likely to contribute significantly to the development of personalised medicine, and targeted preventative approaches. In this review, we consider the current evidence for gene–environment (G–E) interaction in autoimmune disease. Large-scale G–E interaction research efforts, while well-justified, face significant practical and methodological challenges. However, it is clear from the evidence that has already been generated that knowledge on how genes and environment interact at a biological level will be crucial in fully understanding the processes that manifest as autoimmunity.

Noroviruses (NoVs) and rotaviruses (RVs), the two most important causes of viral acute gastroenteritis, are found to recognise histo-blood group antigens (HBGAs) as receptors or ligands for attachment. Human HBGAs are highly polymorphic containing ABO, secretor and Lewis antigens. In addition, both NoVs and RVs are highly diverse in how they recognise these HBGAs. Structural analysis of the HBGA-binding interfaces of NoVs revealed a conserved central binding pocket (CBP) interacting with a common major binding saccharide (MaBS) of HBGAs and a variable surrounding region interacting with additional minor binding saccharides. The conserved CBP indicates a strong selection of NoVs by the host HBGAs, whereas the variable surrounding region explains the diverse recognition patterns of different HBGAs by NoVs and RVs as functional adaptations of the viruses to human HBGAs. Diverse recognition of HBGAs has also been found in bacterial pathogen Helicobacter pylori. Thus, exploratory research into whether such diverse recognitions also occur for other viral and bacterial pathogens that recognise HBGAs is warranted.

Calcinosis cutis (CC) is a type of calcinosis wherein insoluble compounds or salts deposited on the skin. Clinical diagnosis of CC is usually achieved through time consuming histopathological or immunohistochemical procedures, but it can only be empirically identified by experienced practitioners. The use of advanced vibrational spectroscopy has been recently shown to have great potential as a diagnostic technique for various diseased tissues because it analyses the chemical composition of diseased tissue rather than its anatomy and predicts disease progression. This review article includes a summary of the application of Fourier transform infrared (FT-IR) and Raman spectroscopic or microspectroscopic analysis for the rapid diagnosis and identification of the chemical composition of skin calcified deposits in patients with various CC symptoms. Both advanced techniques not only can detect the types of insoluble salts such as calcium phosphate, calcium carbonate, and monosodium urate, and β-carotene in the calcified deposits of human skin tissue but also can directly differentiate the carbonate substitution in the apatite structure of the skin calcified deposits. In particular, the combination of both vibrational techniques may provide complementary information to simultaneously assess the intact components of the calcified deposits. In the future, both FT-IR and Raman vibrational microspectroscopic techniques will become available tools to support the standard test techniques currently used in some clinical diagnoses. Molecular spectroscopy technique is rapidly changing disease diagnosis and management.

Glucagon-like peptide (GLP)-1 is an incretin hormone with several antidiabetic functions including stimulation of glucose-dependent insulin secretion, increase in insulin gene expression and beta-cell survival. Despite the initial technical difficulties and profound inefficiency of direct gene transfer into the pancreas that seriously restricted in vivo gene transfer experiments with GLP-1, recent exploitation of various routes of gene delivery and alternative means of gene transfer has permitted the detailed assessment of the therapeutic efficacy of GLP-1 in animal models of type 2 diabetes (T2DM). As a result, many clinical benefits of GLP-1 peptide/analogues observed in clinical trials involving induction of glucose tolerance, reduction of hyperglycaemia, suppression of appetite and food intake linked to weight loss have been replicated in animal models using gene therapy. Furthermore, GLP-1-centered gene therapy not only improved insulin sensitivity, but also reduced abdominal and/or hepatic fat associated with obesity-induced T2DM with drastic alterations in adipokine profiles in treated subjects. Thus, a comprehensive assessment of recent GLP-1-mediated gene therapy approaches with detailed analysis of current hurdles and resolutions, is discussed.

Adipose-derived stem cells (ASCs) are considered a great alternative source of mesenchymal stem cells (MSCs). Unlike bone marrow stem cells (BMSCs), ASCs can be retrieved in high numbers from lipoaspirate, a by-product of liposuction procedures. Given that ASCs represent an easily accessible and abundant source of multipotent cells, ASCs have garnered attention and curiosity from both scientific and clinical communities for their potential in clinical applications. Furthermore, their unique immunobiology and secretome are attractive therapeutic properties. A decade since the discovery of a stem cell reservoir residing within adipose tissue, ASC-based clinical trials have grown over the years around the world along with assessments made on their safety and efficacy. With the progress of ASCs into clinical applications, the aim towards producing clinical-grade ASCs becomes increasingly important. Several countries have recognised the growing industry of cell therapies and have developed regulatory frameworks to assure their safety. With more research efforts made to understand their effects in both scientific and clinical settings, ASCs hold great promise as a future therapeutic strategy in treating a wide variety of diseases. Therefore, this review seeks to highlight the clinical applicability of ASCs as well as their progress in clinical trials across various medical disciplines.

The identification of multipotent adipose-derived stromal cells (ASC) has raised hope that tissue regeneration approaches established with bone-marrow-derived stromal cells (BMSC) can be reproduced with a cell-type that is far more accessible in large quantities. Recent detailed comparisons, however, revealed subtle functional differences between ASC and BMSC, stressing the concept of a common mesenchymal progenitor existing in a perivascular niche across all tissues. Focussing on bone and cartilage repair, this review summarises recent in vitro and in vivo studies aiming towards tissue regeneration with ASC. Advantages of good accessibility, high yield and superior growth properties are counterbalanced by an inferiority of ASC to form ectopic bone and stimulate long-bone healing along with their less pronounced osteogenic and angiogenic gene expression signature. Hence, particular emphasis is placed on establishing whether stem cell activity of ASC is so far proven and relevant for successful osteochondral regeneration, or whether trophic activity may largely determine therapeutic outcome.

ATR protein kinase is one of the key players in maintaining genome integrity and coordinating of the DNA damage response and repair signalling pathways. Inhibition of ATR prevents signalling from stalled replication forks and enhances the formation of DNA damage, particularly under conditions of replication stress present in cancers. For this reason ATR/CHK1 checkpoint inhibitors can potentiate the effect of DNA cross-linking agents, as evidenced by ATR inhibitors recently entering human clinical trials. This review aims to compile the existing literature on small molecule inhibitors of ATR, both from academia and the pharmaceutical industry, and will provide the reader with a comprehensive summary of this promising oncology target.

Copper is an essential element in many biological processes. The critical functions associated with copper have resulted from evolutionary harnessing of its potent redox activity. This same property also places copper in a unique role as a key modulator of cell signal transduction pathways. These pathways are the complex sequence of molecular interactions that drive all cellular mechanisms and are often associated with the interplay of key enzymes including kinases and phosphatases but also including intracellular changes in pools of smaller molecules. A growing body of evidence is beginning to delineate the how, when and where of copper-mediated control over cell signal transduction. This has been driven by research demonstrating critical changes to copper homeostasis in many disorders including cancer and neurodegeneration and therapeutic potential through control of disease-associated cell signalling changes by modulation of copper–protein interactions. This timely review brings together for the first time the diverse actions of copper as a key regulator of cell signalling pathways and discusses the potential strategies for controlling disease-associated signalling processes using copper modulators. It is hoped that this review will provide a valuable insight into copper as a key signal regulator and stimulate further research to promote our understanding of copper in disease and therapy.

Owing to the limited regenerative capacity of cartilage tissue, cartilage repair remains a challenge in clinical treatment. Tissue engineering has emerged as a promising and important approach to repair cartilage defects. It is well known that material scaffolds are regarded as a fundamental element of tissue engineering. Novel biomaterial scaffolds formed by self-assembling peptides consist of nanofibre networks highly resembling natural extracellular matrices, and their fabrication is based on the principle of molecular self-assembly. Indeed, peptide nanofibre scaffolds have obtained much progress in repairing various damaged tissues (e.g. cartilage, bone, nerve, heart and blood vessel). This review outlines the rational design of peptide nanofibre scaffolds and their potential in cartilage tissue engineering.

Acute kidney injury (AKI) is a serious clinical condition with no effective treatment. Tubular cells are key targets in AKI. Tubular cells and, specifically, proximal tubular cells are extremely rich in mitochondria and mitochondrial changes had long been known to be a feature of AKI. However, only recent advances in understanding the molecules involved in mitochondria biogenesis and dynamics and the availability of mitochondria-targeted drugs has allowed the exploration of the specific role of mitochondria in AKI. We now review the morphological and functional mitochondrial changes during AKI, as well as changes in the expression of mitochondrial genes and proteins. Finally, we summarise the current status of novel therapeutic strategies specifically targeting mitochondria such as mitochondrial permeability transition pore (MPTP) opening inhibitors (cyclosporine A (CsA)), quinone analogues (MitoQ, SkQ1 and SkQR1), superoxide dismutase (SOD) mimetics (Mito-CP), Szeto-Schiller (SS) peptides (Bendavia) and mitochondrial division inhibitors (mdivi-1). MitoQ, SkQ1, SkQR1, Mito-CP, Bendavia and mdivi-1 have improved the course of diverse experimental models of AKI. Evidence for a beneficial effect of CsA on human cardiac ischaemia–reperfusion injury derives from a clinical trial; however, CsA is nephrotoxic. MitoQ and Bendavia have been shown to be safe for humans. Ongoing clinical trials are testing the efficacy of Bendavia in AKI prevention following renal artery percutaneous transluminal angioplasty.

Lymphatic vessels (LVs) are involved in a number of physiological and pathophysiological processes such as fluid homoeostasis, immune surveillance, and resolution of inflammation and wound healing. Lymphangiogenesis, the outgrowth of existing LVs and the formation of new ones, has received increasing attention over the past decade on account of its prominence in organ physiology and pathology, which has been enabled by the development of specific tools to study lymph vessel functions. Several studies have been devoted to renal lymphatic vasculature and lymphangiogenesis in kidney diseases, such as chronic renal transplant dysfunction, primary renal fibrotic disorders, proteinuria, diabetic nephropathy and renal inflammation. This review describes the most recent findings on lymphangiogenesis, with a specific focus on renal lymphangiogenesis and its impact on renal diseases. We suggest renal lymphatics as a possible target for therapeutic interventions in renal medicine to dampen tubulointerstitial tissue remodelling and improve renal functioning.

Muscular dystrophies are a group of diseases characterised by the primary wasting of skeletal muscle, which compromises patient mobility and in the most severe cases originate a complete paralysis and premature death. Existing evidence implicates calcium dysregulation as an underlying crucial event in the pathophysiology of several muscular dystrophies, such as dystrophinopathies, calpainopathies or myotonic dystrophy among others. Duchenne muscular dystrophy is the most frequent myopathy in childhood, and calpainopathy or LGMD2A is the most common form of limb-girdle muscular dystrophy, whereas myotonic dystrophy is the most frequent inherited muscle disease worldwide. In this review, we summarise recent advances in our understanding of calcium ion cycling through the sarcolemma, the sarcoplasmic reticulum and mitochondria, and its involvement in the pathogenesis of these dystrophies. We also discuss some of the clinical implications of recent findings regarding Ca2+ handling as well as novel approaches to treat muscular dystrophies targeting Ca2+ regulatory proteins.

Angptl2 is a multifaceted protein, displaying both physiological and pathological functions, in which scientific and clinical interest is growing exponentially within the past few years. Its physiological functions are not well understood, but angptl2 was first acknowledged for its pro-angiogenic and antiapoptotic capacities. In addition, angptl2 can be considered a growth factor, since it increases survival and expansion of hematopoietic stem cells and may promote vasculogenesis. Finally, angptl2 has an important, but largely unrecognised, physiological role: in the cytosol, angptl2 binds to type 1A angiotensin II receptors and induces their recycling, with recovery of the receptor signal functions. Despite these important physiological properties, angptl2 is better acknowledged for its deleterious pro-inflammatory properties and its contribution in multiple chronic diseases such as cancer, diabetes, atherosclerosis, metabolic disorders and many other chronic diseases. This review aims at presenting an updated description of both the beneficial and deleterious biological properties of angptl2, in addition to its molecular signalling pathways and transcriptional regulation. The multiplicity of diseases in which angptl2 contributes makes it a new highly relevant clinical therapeutic target.

Tubulointerstitial fibrosis and glomerulosclerosis, are a major feature of end stage chronic kidney disease (CKD), characterised by an excessive accumulation of extracellular matrix (ECM) proteins. Transforming growth factor beta-1 (TGF-β1) is a cytokine with an important role in many steps of renal fibrosis such as myofibroblast activation and proliferation, ECM protein synthesis and inflammatory cell infiltration. Endoglin is a TGF-β co-receptor that modulates TGF-β responses in different cell types. In numerous cells types, such as mesangial cells or myoblasts, endoglin regulates negatively TGF-β-induced ECM protein expression. However, recently it has been demonstrated that ‘in vivo’ endoglin promotes fibrotic responses. Furthermore, several studies have demonstrated an increase of endoglin expression in experimental models of renal fibrosis in the kidney and other tissues. Nevertheless, the role of endoglin in renal fibrosis development is unclear and a question arises: Does endoglin protect against renal fibrosis or promotes its development? The purpose of this review is to critically analyse the recent knowledge relating to endoglin and renal fibrosis. Knowledge of endoglin role in this pathology is necessary to consider endoglin as a possible therapeutic target against renal fibrosis.

Humans and other vertebrates exhibit left–right (LR) asymmetric arrangement of the internal organs, and failure to establish normal LR asymmetry leads to internal laterality disorders, including situs inversus and heterotaxy. Situs inversus is complete mirror-imaged arrangement of the internal organs along LR axis, whereas heterotaxy is abnormal arrangement of the internal thoraco-abdominal organs across LR axis of the body, most of which are associated with complex cardiovascular malformations. Both disorders are genetically heterogeneous with reduced penetrance, presumably because of monogenic, polygenic or multifactorial causes. Research in genetics of LR asymmetry disorders has been extremely prolific over the past 17 years, and a series of loci and disease genes involved in situs inversus and heterotaxy have been described. The review highlights the classification, chromosomal abnormalities, pathogenic genes and the possible mechanism of human LR asymmetry disorders.