Progressive myoclonus epilepsies (PMEs) are a group of genetic neurological disorders characterised by the occurrence of epileptic seizures, myoclonus and progressive neurological deterioration including cerebellar involvement and dementia. The primary cause of PMEs is variable and alterations in the corresponding mutated genes determine the progression and severity of the disease. In most cases, they

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide, with reported incidences of ~800 000 cases each year. One of the critical determinants in patient response to radiotherapy, particularly for oropharyngeal cancers, is human papillomavirus (HPV) status where HPV-positive patients display improved survival rates and outcomes particularly because of increased responsiveness

DNA damage response (DDR) pathway prevents high level endogenous and environmental DNA damage being replicated and passed on to the next generation of cells via an orchestrated and integrated network of cell cycle checkpoint signalling and DNA repair pathways. Depending on the type of damage, and where in the cell cycle it occurs different pathways are involved, with the ATM-CHK2-p53 pathway controlling

Most commonly described as sporadic, pulmonary adenocarcinoma with enteric differentiation (PAED) is a rare variant of invasive lung cancer recently established and recognised by the World Health Organization. This tumour is highly heterogeneous and shares several morphological features with pulmonary and colorectal adenocarcinomas. Our objective is to summarise current research on PAED, focusing on

Autosomal dominant polycystic kidney disease (ADPKD) is the most common monogenic kidney disease and is caused by heterozygous germ-line mutations in either PKD1 (85%) or PKD2 (15%). It is characterised by the formation of numerous fluid-filled renal cysts and leads to adult-onset kidney failure in ~50% of patients by 60 years. Kidney cysts in ADPKD are focal and sporadic, arising from the clonal proliferation

Muscular dystrophy is a group of genetic disorders characterised by degeneration of muscles. Different forms of muscular dystrophy can show varying phenotypes with a wide range of age, severity and location of muscle deterioration. Many palliative care options are available for muscular dystrophy patients, but no curative treatment is available. Exon-skipping therapy aims to induce skipping of exons

Warburg and coworkers' observation of altered glucose metabolism in tumours has been neglected for several decades, which, in part, was because of an initial misinterpretation of the basis of their finding. Following the realisation that genetic alterations are often linked to metabolism, and that the tumour micro-environment imposes different demands on cancer cells, has led to a reinvestigation of

Hepatitis C virus represents a global pathogen of human health significance. In the space of less than three decades, we have witnessed the discovery of the virus, a growing understanding of the structure and biology of the viral-encoded proteins and their interaction with the host cell and the sequencing of the viral genome. Most importantly, we have moved from early therapeutic strategies aimed at

Mosquitoes are haematophagous vectors for hundreds of pathogenic viruses that are aetiological agents of human diseases. In nature, mosquito-borne viruses maintain a lifecycle between mosquitoes and vertebrate animals. Viruses are acquired by a naive mosquito from an infected host by blood meals and then propagate extensively in the mosquito's tissues. This mosquito then becomes a virus reservoir and

Deviations from the precisely coordinated programme of human head development can lead to craniofacial and orofacial malformations often including a variety of dental abnormalities too. Although the aetiology is still unknown in many cases, during the last decades different intracellular signalling pathways have been genetically linked to specific disorders. Among these pathways, the RAS/extracellular

Gelsolin (GSN), one of the most abundant actin-binding proteins, is involved in cell motility, shape and metabolism. As a member of the GSN superfamily, GSN is a highly structured protein in eukaryotic cells that can be regulated by calcium concentration, intracellular pH, temperature and phosphatidylinositol-4,5-bisphosphate. GSN plays an important role in cellular mechanisms as well as in different

Circulating cell-free DNA (cfDNA) consists of small fragments of DNA that circulate freely in the bloodstream. In cancer patients, a fraction of cfDNA is derived from tumour cells, therefore containing the same genetic and epigenetic alterations, and is termed circulating cell-free tumour DNA. The potential use of cfDNA, the so-called 'liquid biopsy', as a non-invasive cancer biomarker has recently

The human animal type melanoma (ATM) is a rare subtype of melanoma characterised by the proliferation of pigmented dermal epithelioid and spindled melanocytes. However, this variant of melanoma is still lacking a precise nosography definition and classification for the difficulty to be distinguished from other more common melanocytic lesions, as well as for its peculiar biological behaviour. On the

The field of Traditional Chinese Medicine (TCM) represents a vast and largely untapped resource for modern medicine. Exemplified by the success of the antimalarial artemisinin, the recent years have seen a rapid increase in the understanding and application of TCM-derived herbs and formulations for evidence-based therapy. In this review, we summarise and discuss the developmental history, clinical

Fever-associated seizures or epilepsy (FASE) is primarily characterised by the occurrence of a seizure or epilepsy usually accompanied by a fever. It is common in infants and children, and generally includes febrile seizures (FS), febrile seizures plus (FS+), Dravet syndrome (DS) and genetic epilepsy with febrile seizures plus (GEFSP). The aetiology of FASE is unclear. Genetic factors may play crucial

Oestrogen-progesterone signalling is highly versatile and critical for the maintenance of healthy endometrium in humans. The genomic and nongenomic signalling cascades initiated by these hormones in differentiated cells of endometrium have been the primary focus of research since 1920s. However, last decade of research has shown a significant role of stem cells in the maintenance of a healthy endometrium

Cell-free DNA (cfDNA) is present in various body fluids and originates mostly from blood cells. In specific conditions, circulating cfDNA might be derived from tumours, donor organs after transplantation or from the foetus during pregnancy. The analysis of cfDNA is mainly used for genetic analyses of the source tissue -tumour, foetus or for the early detection of graft rejection. It might serve also

The protein kinase R (PKR, also called EIF2AK2) is an interferon-inducible double-stranded RNA protein kinase with multiple effects on cells that plays an active part in the cellular response to numerous types of stress. PKR has been extensively studied and documented for its relevance as an antiviral agent and a cell growth regulator. Recently, the role of PKR related to metabolism, inflammatory processes

Fragile X mental retardation 1 (FMR1) full-mutation expansion causes fragile X syndrome. Trans-generational fragile X syndrome transmission can be avoided by preimplantation genetic diagnosis (PGD). We describe a robust PGD strategy that can be applied to virtually any couple at risk of transmitting fragile X syndrome. This novel strategy utilises whole-genome amplification, followed by triplet-primed

Wilms tumour (WT) is the most common paediatric kidney cancer and affects approximately one in 10 000 children. The tumour is associated with undifferentiated embryonic lesions called nephrogenic rests (NRs) or, when diffuse, nephroblastomatosis. WT or NRs can occur in both kidneys, termed bilateral disease, found in only 5-8% of cases. Management of bilateral WT presents a major clinical challenge

Amyotrophic lateral sclerosis (ALS) is a severe neuromuscular disease characterised by a progressive loss of motor neurons that usually results in paralysis and death within 2 to 5 years after disease onset. The pathophysiological mechanisms involved in ALS remain largely unknown and to date there is no effective treatment for this disease. Here, we review clinical and experimental evidence suggesting

Biologics are a promising new class of drugs based on complex macromolecules such as proteins and nucleic acids. However, delivery of these macromolecules into the cytoplasm of target cells remains a significant challenge. Here we present one potential solution: bacterial nanomachines that have evolved over millions of years to efficiently deliver proteins and nucleic acids across cell membranes and

Ischaemic heart disease and stroke are vascular events with serious health consequences worldwide. Recent genetic and epigenetic techniques have revealed many genetic determinants of these vascular events and simplified the approaches to research focused on ischaemic heart disease and stroke. The pathogenetic mechanisms of ischaemic heart disease and stroke are complex, with mitochondrial involvement

Cancer metastasis occurs through local invasion of circulating tumour cells (CTCs), intravasation, transportation to distant sites, and their extravasation followed by colonisation at secondary sites. Epithelial-mesenchymal transition (EMT) is a normal developmental phenomenon, but its aberrant activation confers tumour cells with enhanced cell motility, metastatic properties, resistant to therapies

Gastric cancer is an inflammation-associated malignancy aetiologically related to infection with the bacterium, Helicobacter pylori, which is considered a necessary but insufficient cause. Unless treated, H. pylori causes life-long acute and chronic gastric inflammation resulting in progressive gastric mucosal damage that may result in gastric cancer. The rate of progression from superficial gastritis

Limb-girdle muscular dystrophy type 2A (LGMD2A) is characterised by muscle wasting and progressive degeneration of proximal muscles because of mutations in the CAPN3 gene. However, the underlying pathophysiological mechanisms of muscle degeneration are still not well understood. The objective of this study was to assess the relevance of genes with differential expression in the muscle of LGMD2A patients

Persistent infection with high-risk human papillomavirus (HPV) genotypes is the leading cause of cervical cancer development. To this end several studies have focused on designing molecular assays for HPV genotyping, which are considered as the gold standard for the early diagnosis of HPV infection. Moreover, the tendency of HPV DNA to be integrated into the host chromosome is a determining event for

Triple-negative breast cancer (TNBC) is a heterogeneous group of tumours characterised by lack of expression of oestrogen-, progesterone- and human epidermal growth factor receptors. TNBC, which represents approximately 15% of all mammary tumours, has a poor prognosis because of an aggressive behaviour and the lack of specific treatment. Accordingly, TNBC has become a major focus of research into breast

Acute intermittent porphyria (AIP) is an autosomal dominant metabolic disease caused by hepatic deficiency of hydroxymethylbilane synthase (HMBS), the third enzyme of the heme synthesis pathway. The dominant clinical feature is acute neurovisceral attack associated with high production of potentially neurotoxic porphyrin precursors due to increased hepatic heme consumption. Current Standard of Care

Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease. Non-alcoholic steatohepatitis (NASH) is a more severe form of NAFLD and causes subsequent pathological changes including cirrhosis and hepatocellular carcinoma. Inflammation is the key pathological change in NASH and involves a series of cytokines and chemokines. The C-X-C motif chemokine 10 (CXCL10), which

Eye-derived fluids, including tears, aqueous humour and vitreous humour often contain molecular signatures of ocular disease states. These signatures can be composed of cytokines, chemokines, growth factors, proteases and soluble receptors. However, the small quantities (<10 µl) of these fluids severely limit the detection of these proteins by traditional enzyme-linked immunosorbent assay or Western

UNLABELLED Steatosis is an early characteristic in the pathogenesis of fatty liver disease (FLD). Mechanisms of hepatic steatosis are aetiology-dependent. Activation of autophagy in liver ameliorates hepatic steatosis. A modulation of hepatic autophagy affects the degree of hepatocyte steatosis and the progression of FLD as demonstrated by pre-clinical models and clinical trials. This review summarises

Current therapies to treat Alzheimer's disease (AD) are focused on ameliorating symptoms instead of treating the underlying causes of AD. The accumulation of amyloid β (Aβ) oligomers, whether by an increase in production or by a decrease in clearance, has been described as the seed that initiates the pathological cascade in AD. Developing therapies to target these species is a vital step in improving

Necrotising enterocolitis (NEC) is an uncommon, but devastating intestinal inflammatory disease that predominantly affects preterm infants. NEC is sometimes dubbed the spectre of neonatal intensive care units, as its onset is insidiously non-specific, and once the disease manifests, the damage inflicted on the baby's intestine is already disastrous. Subsequent sepsis and multi-organ failure entail

Genetic characterization of individuals at risk of Alzheimer's disease (AD), i.e. people having amyloid deposits in the brain without symptoms, people suffering from subjective cognitive decline (SCD) or mild cognitive impairment (MCI), has spurred the interests of researchers. However, their pre-dementia genetic profile remains mostly unexplored. In this study, we reviewed the loci related to phenotypes

The human follicular fluid (HFF) contains molecules and proteins that may affect follicle growth, oocyte maturation and competence acquiring. Despite the numerous studies, an integrated broad overview on biomolecular and patho/physiological processes that are proved or supposed to take place in HFF during folliculogenesis and oocyte development is still missing. In this review we report, for the first

Trimethylamine (TMA) is a tertiary amine with a characteristic fishy odour. It is synthesised from dietary constituents, including choline, L-carnitine, betaine and lecithin by the action of microbial enzymes during both healthy and diseased conditions in humans. Trimethylaminuria (TMAU) is a disease typified by its association with the characteristic fishy odour because of decreased TMA metabolism

Limb-girdle muscular dystrophy type 2A (LGMD2A) is a form of muscular dystrophy caused by mutations in calpain 3 (CAPN3). Several studies have implicated Ca2+ dysregulation as an underlying event in several muscular dystrophies, including LGMD2A. In this study we used mouse and human myotube cultures, and muscle biopsies in order to determine whether dysfunction of sarco/endoplasmatic Ca2+-ATPase (SERCA)

Cardiovascular diseases are the leading cause of death in developed countries. The aetiology is currently multifactorial, thus making them very difficult to prevent. Preclinical models of atherothrombotic diseases, including vulnerable plaque-associated complications, are now providing significant insights into pathologies like atherosclerosis, and in combination with the most recent advances in new

Transmissible spongiform encephalopathies (TSEs), or prion diseases, are fatal neurodegenerative disorders characterised by long incubation period, short clinical duration, and transmissibility to susceptible species. Neuronal loss, spongiform changes, gliosis and the accumulation in the brain of the misfolded version of a membrane-bound cellular prion protein (PrP(C)), termed PrP(TSE), are diagnostic

miR-124, a brain-specific microRNA, was originally considered as a key regulator in neuronal differentiation and the development of the nervous system. Here we showed that miR-124 expression was suppressed in patients with epilepsy and rats after drug induced-seizures. Intrahippocampal administration of a miR-124 duplex led to alleviated seizure severity and prolonged onset latency in two rat models

The GATA family of transcription factors consists of six proteins (GATA1-6) which are involved in a variety of physiological and pathological processes. GATA1/2/3 are required for differentiation of mesoderm and ectoderm-derived tissues, including the haematopoietic and central nervous system. GATA4/5/6 are implicated in development and differentiation of endoderm- and mesoderm-derived tissues such

Arboviruses are pathogens that widely affect the health of people in different communities around the world. Recently, a few successful approaches toward production of effective vaccines against some of these pathogens have been developed, but treatment and prevention of the resulting diseases remain a major health and research concern. The arbovirus infection and replication processes are complex

The translation initiation factor eIF4E mediates a rate-limiting process that drives selective translation of many oncongenic proteins such as cyclin D1, survivin and VEGF, thereby contributing to tumour growth, metastasis and therapy resistance. As an essential regulatory hub in cancer signalling network, many oncogenic signalling pathways appear to converge on eIF4E. Therefore, targeting eIF4E-mediated

Regenerative medicine using patient's own stem cells (SCs) to repair dysfunctional tissues is an attractive approach to complement surgical and pharmacological treatments for aging and degenerative disorders. Recently, dental SCs have drawn much attention owing to their accessibility, plasticity and applicability for regenerative use not only for dental, but also other body tissues. In ophthalmology

Alongside advancements in gene therapy for inherited immune disorders, the need for effective alternative therapeutic options for other conditions has resulted in an expansion in the field of research for T cell gene therapy. T cells are easily obtained and can be induced to divide robustly ex vivo, a characteristic that allows them to be highly permissible to viral vector-mediated introduction of

Polydactyly is one of the most common inherited limb abnormalities, characterised by supernumerary fingers or toes. It results from disturbances in the normal programme of the anterior-posterior axis of the developing limb, with diverse aetiology and variable inter- and intra-familial clinical features. Polydactyly can occur as an isolated disorder (non-syndromic polydactyly) or as a part of an anomaly

The Rho/ROCK pathway is involved in numerous pivotal cellular processes that have made it an area of intense study in cancer medicine, however, Rho-associated coiled-coil containing protein kinase (ROCK) inhibitors are yet to make an appearance in the clinical cancer setting. Their performance as an anti-cancer therapy has been varied in pre-clinical studies, however, they have been shown to be effective

Heart disease, including valve pathologies, is the leading cause of death worldwide. Despite the progress made thanks to improving transplantation techniques, a perfect valve substitute has not yet been developed: once a diseased valve is replaced with current technologies, the newly implanted valve still needs to be changed some time in the future. This situation is particularly dramatic in the case

Epstein-Barr virus (EBV) was first discovered 50 years ago as an oncogenic gamma-1 herpesvirus and infects more than 90% of the worldwide adult population. Nasopharyngeal carcinoma (NPC) poses a serious health problem in southern China and is one of the most common cancers among the Chinese. There is now strong evidence supporting a role for EBV in the pathogenesis of NPC. Latent membrane protein 1

In the mammalian testis, spermatogenesis is a highly coordinated process of germ cell development, which ends with the release of 'mature' spermatozoa. The fine regulation of spermatogenesis is strictly dependent on sex steroid hormones, which orchestrate the cellular and molecular events underlying normal development of germ cells. Sex steroids actions also rely on the control of germ cell survival

Cell-penetrating peptides (CPPs) are reliable vehicles for the target-selective intracellular delivery of therapeutic agents. The identification and application of numerous intrinsically bioactive CPPs, now designated as bioportides, is further endorsement of the tremendous clinical potential of CPP technologies. The refinement of proteomimetic bioportides, particularly sequences that mimic cationic

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

The Hippo signalling is emerging as a tumour suppressor pathway whose function is regulated by an intricate network of intracellular and extracellular cues. Defects in the signal cascade lead to the activation of the Hippo transducers TAZ and YAP. Compelling preclinical evidence showed that TAZ/YAP are often aberrantly engaged in breast cancer (BC), where their hyperactivation culminates into a variety

Methylation of the fragile X mental retardation 1 (FMR1) exon 1/intron 1 boundary positioned fragile X related epigenetic element 2 (FREE2), reveals skewed X-chromosome inactivation (XCI) in fragile X syndrome full mutation (FM: CGG > 200) females. XCI skewing has been also linked to abnormal X-linked gene expression with the broader clinical impact for sex chromosome aneuploidies (SCAs). In this study

Muscle fibres are very specialised cells with a complex structure that requires a high level of organisation of the constituent proteins. For muscle contraction to function properly, there is a need for not only sarcomeres, the contractile structures of the muscle fibre, but also costameres. These are supramolecular structures associated with the sarcolemma that allow muscle adhesion to the extracellular

Since the discovery of adipose-derived stem cells (ASCs), there have been high expectations of their putative clinical use. Recent advances support these expectations, and it is expected that the transition from pre-clinical and clinical studies to implementation as a standard treatment modality is imminent. However ASCs must be isolated and expanded according to good manufacturing practice guidelines

White sponge nevus (WSN) in the oral mucosa is a rare autosomal dominant genetic disease. The involved mucosa is white or greyish, thickened, folded and spongy. The genes associated with WSN include mutant cytokeratin keratin 4 (KRT4) and keratin 13 (KRT13). In recent years, new cases of WSN and associated mutations have been reported. Here, we summarise the recent progress in our understanding of