Negative pressure wound therapy (NPWT) has significantly advanced wound care and continues to find new applications. Its effects at a molecular level however, remain a subject of debate. The aim of this systematic review is to summarize the current evidence regarding the molecular mechanisms of action of NPWT. Medline, Embase, EBSCO databases and clinical trial registries were searched from inception to January 2023. Clinical studies, animal models or in-vitro studies that quantitatively or semi-quantitatively evaluated the influence of NPWT on growth factors, cytokine or gene-expression in the circulation or wound-bed were included. Risk of Bias assessment was performed using the RoBANS tool for non-randomized studies, the COCHRANE's Risk of Bias 2(ROB-2) tool for randomized clinical studies, OHAT tool for in-vitro studies or the SYRCLE tool for animal model studies. A descriptive summary was collated and the aggregated data is presented as a narrative synthesis. This review included 19 clinical studies, 11 animal studies and 3 in-vitro studies. The effects of NPWT on 43 biomarkers and 17 gene expressions were studied across included studies. NPWT stimulates modulation of numerous local and circulating cytokines and growth factor expressions to promote an anti-inflammatory profile. This is most likely achieved by downregulation of TNFα, upregulation of VEGF, TGF-β and fibronectin.

Aging is the most prominent risk factor for many diseases, which is considered to be a complicated biological process. The rate of aging depends on the effectiveness of important mechanisms such as the protection of DNA from free radicals, which protects the structural and functional integrity of cells and tissues. In any organism, not all organs may age at the same rate. Slowing down primary aging and reaching maximum lifespan is the most basic necessity. In this process, it may be possible to slow down or stabilise some diseases by using the compounds for both dietary and pharmacological purposes. Natural compounds with antioxidant and anti-inflammatory effects, mostly plant-based nutraceuticals, are preferred in the treatment of age-related chronic diseases and can also be used for other diseases. An increasing number of long-term studies on synthetic and natural compounds aim to elucidate preclinically and clinically the mechanisms underlying being healthy and prolongation of life. To delay age-related diseases and prolong the lifespan, it is necessary to take these compounds with diet or pharmaceuticals, along with detailed toxicological results. In this review, the most promising and utilised compounds will be highlighted and it will be discussed whether they have toxic effects in short/long-term use, although they are thought to be used safely.

The difficulty of diagnosing prostate cancer (PC) with the available biomarkers frequently leads to over-diagnosis and overtreatment of PC, underscoring the need for novel molecular signatures. The purpose of this review is to provide a summary of the currently available cellular metabolomics for PC molecular signatures. A comprehensive search on PubMed was conducted to find studies published between January 2004 and August 2022 that reported biomarkers for PC detection, development, aggressiveness, recurrence and treatment response. Although potential studies have reported the presence of distinguishing molecules that can distinguish between benign and cancerous prostate tissue. However, there are few studies looking into signature molecules linked to disease development, therapy response or tumour recurrence. The majority of these studies use high-dimensional datasets, and the number of potential metabolites investigated frequently exceeds the size of the available samples. In light of this, pre-analytical, statistical, methodological and confounding factors such as antiandrogen therapy (NAT) may also be linked to the identified chemometric multivariate differences between PC and relevant control samples in the datasets. Despite the methodological and procedural challenges, a range of methodological groups and processes have consistently identified a number of signature metabolites and pathways that appear to imply a substantial involvement in the cellular metabolomics of PC for tumour formation and recurrence.

The nuclear factor of κ-light chain of enhancer-activated B cells (NF-κB) signaling pathway, which is conserved in invertebrates, plays a significant role in human diseases such as inflammation-related diseases and carcinogenesis. Angiogenesis refers to the growth of new capillary vessels derived from already existing capillaries and postcapillary venules. Maintaining normal angiogenesis and effective vascular function is a prerequisite for the stability of organ tissue function, and abnormal angiogenesis often leads to a variety of diseases. It has been suggested that NK-κB signalling molecules under pathological conditions play an important role in vascular differentiation, proliferation, apoptosis and tumourigenesis by regulating the transcription of multiple target genes. Many NF-κB inhibitors are being tested in clinical trials for cancer treatment and their effect on angiogenesis is summarised. In this review, we will summarise the role of NF-κB signalling in various neovascular diseases, especially in tumours, and explore whether NF-κB can be used as an attack target or activation medium to inhibit tumour angiogenesis.

Reactive oxygen species (ROS) play an essential role in regulating various functions of organisms such as gene transcription, signalling transduction and immune response. However, overproduction of ROS can lead to oxidative stress, which is related to various ageing diseases including eye and brain degenerative diseases. Ocular measurements have recently been suggested as potential sources of biomarkers for the early detection of brain neurodegenerative diseases. MicroRNAs (miRNAs) are useful biomarkers for various diseases including degenerative diseases. miRNAs play an important role in the oxidative stress mechanisms of ageing diseases. In this paper, the role of miRNAs related to oxidative stress mechanisms in four ageing diseases, Parkinson's disease (PD), Alzheimer's disease (AD), glaucoma and age-related macular degeneration was reviewed. The common miRNA biomarkers related to the four diseases were also discussed. The results show that these eye and brain ageing diseases share many common miRNA biomarkers. It indicates that the ocular condition may be a prognostic biomarker for PD or AD patients. When a patient's eye condition changes, this can be a warning of a change in PD or AD status.

Helicobacter pylori (H. pylori) is a worldwide spread bacterium, co-evolving with humans for at least 100 000 years. Despite the uncertainty about the mode of H. pylori transmission, the development of intra-gastric and extra-gastric diseases is attributed to this bacterium. The morphological transformation and production of heterogenic virulence factors enable H. pylori to overcome the harsh stomach environment. Using numerous potent disease-associated virulence factors makes H. pylori a prominent pathogenic bacterium. These bacterial determinants are adhesins (e.g., blood group antigen-binding adhesin (BabA)/sialic acid-binding adhesin (SabA)), enzymes (e.g., urease), toxins (e.g., vacuolating cytotoxin A (VacA)), and effector proteins (e.g., cytotoxin-associated gene A (CagA)) involved in colonisation, immune evasion, and disease induction. H. pylori not only cleverly evades the immune system but also robustly induces immune responses. This insidious bacterium employs various strategies to evade human innate and adaptive immune responses, leading to a life-long infection. Owing to the alteration of surface molecules, innate immune receptors couldn't recognise this bacterium; moreover, modulation of effector T cells subverts adaptive immune response. Most of the infected humans are asymptomatic and only a few of them present severe clinical outcomes. Therefore, the identification of virulence factors will pave the way for the prediction of infection severity and the development of an effective vaccine. H. pylori virulence factors are hereby comprehensively reviewed and the bacterium evasion from the immune response is properly discussed.

Inflammation and immune evasion are major key players in breast cancer (BC) progression. Recently, the FDA approved the use of anti-programmed death-ligand 1 antibody (anti-PD-L1) and phosphoinositide 3-kinase (PI3K) inhibitors against aggressive BC. Despite the paradigm shift in BC treatments, patients still suffer from resistance, recurrence and serious immune-related adverse events. These obstacles require unravelling of the hidden molecular contributors for such therapy failure hence yielding therapeutics that are at least as efficient yet safer. Inflammasome pathway is activated when the pattern recognition receptor senses danger signals (danger-associated molecular patterns) from damagedRdying cells or pathogen-associated molecular patterns found in microbes, leading to secretion of the active pro-inflammatory cytokines interleukin-1β (IL-1β) and interleukin-18 (IL-18). It has been shown throughout numerous studies that inflammasome pathway enhanced invasion, metastasis, provoked BC progression and therapy resistance. Additionally, inflammasomes upregulated the proliferative index ki67 and enhanced PD-L1 expression leading to immunotherapy resistance. IL-1β contributed to significant decrease in oestrogen receptor levels and promoted BC chemo-resistance. High levels of IL-18 in sera of BC patients were associated with worst prognosis. Stimulation of purinergic receptors and modulation of adipokines in obese subjects activated inflammasomes that evoked radiotherapy resistance and BC progression. The micro RNA miR-223-3p attenuated the inflammasome over-expression leading to lowered tumour volume and lessened angiogenesis in BC. This review sheds the light on the molecular pathways of inflammasomes and their impacts in distinct BC subtypes. In addition, it highlights novel strategies in treatment and prevention of BC.

Breast cancer is a high-risk disease with a high mortality rate among women. Chemotherapy plays an important role in the treatment of breast cancer. However, chemotherapy eventually results in tumours that are resistant to drugs. In recent years, many studies have revealed that the activation of Wnt/β-catenin signalling is crucial for the emergence and growth of breast tumours as well as the development of drug resistance. Additionally, drugs that target this pathway can reverse drug resistance in breast cancer therapy. Traditional Chinese medicine has the properties of multi-target and tenderness. Therefore, integrating traditional Chinese medicine and modern medicine into chemotherapy provides a new strategy for reversing the drug resistance of breast tumours. This paper mainly reviews the possible mechanism of Wnt/β-catenin in promoting the process of breast tumour drug resistance, and the progress of alkaloids extracted from traditional Chinese medicine in the targeting of this pathway in order to reverse the drug resistance of breast cancer.

Studies of autism spectrum disorder (ASD) related to exposure to toxic levels of dietary phosphate are lacking. Phosphate toxicity from dysregulated phosphate metabolism can negatively impact almost every major organ system of the body, including the central nervous system. The present paper used a grounded theory-literature review method to synthesise associations of dysregulated phosphate metabolism with the aetiology of ASD. Cell signalling in autism has been linked to an altered balance between phosphoinositide kinases, which phosphorylate proteins, and the counteracting effect of phosphatases in neuronal membranes. Glial cell overgrowth in the developing ASD brain can lead to disturbances in neuro-circuitry, neuroinflammation and immune responses which are potentially related to excessive inorganic phosphate. The rise in ASD prevalence has been suggested to originate in changes to the gut microbiome from increasing consumption of additives in processed food, including phosphate additives. Ketogenic diets and dietary patterns that eliminate casein also reduce phosphate intake, which may account for many of the suggested benefits of these diets in children with ASD. Dysregulated phosphate metabolism is causatively linked to comorbid conditions associated with ASD such as cancer, tuberous sclerosis, mitochondrial dysfunction, diabetes, epilepsy, obesity, chronic kidney disease, tauopathy, cardiovascular disease and bone mineral disorders. Associations and proposals presented in this paper offer novel insights and directions for future research linking the aetiology of ASD with dysregulated phosphate metabolism and phosphate toxicity from excessive dietary phosphorus intake.

A period of about a decade has been estimated to pass for the emergence of a new infectious strain of a virus that may lead to the occurrence of a pandemic one. It is now suggested that the variants of the 1918 H1N1 and coronavirus disease-19 pandemics could have existed in humans after the initial cross-species introduction to humans and underwent multiple low-level seasonal epidemics before the occurrence of their outbreaks. They share similarities in the continuation, widespreadness due to high transmissibility, high fatality rate and clinical symptoms. They are assumed to share a similar principle of a zoonotic source and a cross-species pathway for transmission. They show some similarities in their pathogenesis with other enveloped viruses: Severe Acute Respiratory Syndrome Coronavirus-1 (SARS-CoV-1), Middle East respiratory syndrome coronavirus (MERS-CoV), human immunodeficiency virus, Ebola, Lassa and measles viruses. The highly pathogenic nature of these viruses and their genetic variants may depend on their binding affinity for host cell receptors, whereby they efficiently circumvent or block host cell immune responses triggered by cytokines (interferon). High transmission rates and viral pathogenicity are attributed to glycan moieties that facilitate virus binding to host multiple receptors and cell entry, thereby helping viruses to evade immune recognition and response. Also, mucosa glycotopes are a matter of concern that play as primary sites for virus attachment and body entry. Finding general lectins or ligands that block the viral–host receptors interaction or identifying individual glycotopes is the therapeutic and prognosis topic that demands the main focus.

Timothy syndrome (TS), characterised by multiple system malfunction especially the prolonged corrected QT interval and synchronised appearance of hand/foot syndactyly, is an extremely rare disease affecting early life with devastating arrhythmia. In this work, firstly, the various mutations in causative gene CACNA1C encoding cardiac L-type voltage-gated calcium channel (LTCC), regard with the genetic pathogeny and nomenclature of TS are reviewed. Secondly, the expression profile and function of CACNA1C gene encoding Cav1.2 proteins, and its gain-of-function mutation in TS leading to multiple organ disease phenotypes especially arrhythmia are discussed. More importantly, we focus on the altered molecular mechanism underlying arrhythmia in TS, and discuss about how LTCC malfunction in TS can cause disorganised calcium handling with excessive intracellular calcium and its triggered dysregulated excitation–transcription coupling. In addition, current therapeutics for TS cardiac phenotypes including LTCC blockers, beta-adrenergic blocking agents, sodium channel blocker, multichannel inhibitors and pacemakers are summarised. Eventually, the research strategy using patient-specific induced pluripotent stem cells is recommended as one of the promising future directions for developing therapeutic approaches. This review updates our understanding on the research progress and future avenues to study the genetics and molecular mechanism underlying the pathogenesis of devastating arrhythmia within TS, and provides novel insights for developing therapeutic measures.

This review discusses current research on acute paediatric leukaemia, the leukaemic bone marrow (BM) microenvironment and recently discovered therapeutic opportunities to target leukaemia–niche interactions. The tumour microenvironment plays an integral role in conferring treatment resistance to leukaemia cells, this poses as a key clinical challenge that hinders management of this disease. Here we focus on the role of the cell adhesion molecule N-cadherin (CDH2) within the malignant BM microenvironment and associated signalling pathways that may bear promise as therapeutic targets. Additionally, we discuss microenvironment-driven treatment resistance and relapse, and elaborate the role of CDH2-mediated cancer cell protection from chemotherapy. Finally, we review emerging therapeutic approaches that directly target CDH2-mediated adhesive interactions between the BM cells and leukaemia cells.

Breast cancer was the most commonly diagnosed cancer worldwide in 2020. Greater understanding of the factors which promote tumour progression, metastatic development and therapeutic resistance is needed. In recent years, a distinct microbiome has been detected in the breast, a site previously thought to be sterile. Here, we review the clinical and molecular relevance of the oral anaerobic bacterium Fusobacterium nucleatum in breast cancer. F. nucleatum is enriched in breast tumour tissue compared with matched healthy tissue and has been shown to promote mammary tumour growth and metastatic progression in mouse models. Current literature suggests that F. nucleatum modulates immune escape and inflammation within the tissue microenvironment, two well-defined hallmarks of cancer. Furthermore, the microbiome, and F. nucleatum specifically, has been shown to affect patient response to therapy including immune checkpoint inhibitors. These findings highlight areas of future research needed to better understand the influence of F. nucleatum in the development and treatment of breast cancer.

The term ‘autophagy’ literally translates to ‘self-eating’ and alterations to autophagy have been identified as one of the several molecular changes that occur with aging in a variety of species. Autophagy and aging, have a complicated and multifaceted relationship that has recently come to light thanks to breakthroughs in our understanding of the various substrates of autophagy on tissue homoeostasis. Several studies have been conducted to reveal the relationship between autophagy and age-related diseases. The present review looks at a few new aspects of autophagy and speculates on how they might be connected to both aging and the onset and progression of disease. Additionally, we go over the most recent preclinical data supporting the use of autophagy modulators as age-related illnesses including cancer, cardiovascular and neurodegenerative diseases, and metabolic dysfunction. It is crucial to discover important targets in the autophagy pathway in order to create innovative therapies that effectively target autophagy. Natural products have pharmacological properties that can be therapeutically advantageous for the treatment of several diseases and they also serve as valuable sources of inspiration for the development of possible new small-molecule drugs. Indeed, recent scientific studies have shown that several natural products including alkaloids, terpenoids, steroids, and phenolics, have the ability to alter a number of important autophagic signalling pathways and exert therapeutic effects, thus, a wide range of potential targets in various stages of autophagy have been discovered. In this review, we summarised the naturally occurring active compounds that may control the autophagic signalling pathways.

Cancer metastasis is the primary cause of cancer-related deaths. The seeding of primary tumours at a secondary site is a highly inefficient process requiring substantial alterations in the genetic architecture of cancer cells. These alterations include significant changes in global gene expression patterns. MicroRNAs are small, non-protein coding RNAs which play a central role in regulating gene expression. Here, we focus on microRNA determinants of cancer metastasis and examine microRNA dysregulation in metastatic cancer cells. We dissect the metastatic process in a step-wise manner and summarise the involvement of microRNAs at each step. We also discuss the advantages and limitations of different microRNA-based strategies that have been used to target metastasis in pre-clinical models. Finally, we highlight current clinical trials that use microRNA-based therapies to target advanced or metastatic tumours.

Hepatitis B virus (HBV) infection led to 66% liver deaths world-wide in year 2015. Thirty-seven per cent of these deaths were the result of chronic hepatitis B (CHB)-associated hepatocellular carcinoma (HCC). Although early diagnosis of HCC improves survival, early detection is rare. Methylation of HBV DNA including covalently closed circular DNA (cccDNA) is more often encountered in HCC cases than those in CHB and cirrhosis. Three typical CpG islands within the HBV genome are the common sites for methylation. The HBV cccDNA methylation affects the viral replication and protein expression in the course of infection and may associate with the disease pathogenesis and HCC development. We review the current findings in HBV DNA methylation that provide insights into its role in HCC diagnosis.

Glioblastoma (GBM) is the most frequent adult malignant brain tumour and despite different therapeutic efforts, the median overall survival still ranges from 14 to 18 months. Thus, new therapeutic strategies are urgently needed. However, the identification of cancer-specific targets is particularly challenging in GBM, due to the high heterogeneity of this tumour in terms of histopathological, molecular, genetic and epigenetic features. Telomerase reactivation is a hallmark of malignant glioma. An activating mutation of the hTERT gene, encoding for the active subunit of telomerase, is one of the molecular criteria to establish a diagnosis of GBM, IDH-wildtype, in the 2021 WHO classification of central nervous system tumours. Telomerase inhibition therefore represents, at least theoretically, a promising strategy for GBM therapy: pharmacological compounds, as well as direct gene expression modulation therapies, have been successfully employed in in vitro and in vivo settings. Unfortunately, the clinical applications of telomerase inhibition in GBM are currently scarce. The aim of the present systematic review is to provide an up-to-date report on the studies investigating telomerase inhibition as a therapeutic strategy for malignant glioma in order to foster the future translational and clinical research on this topic.