Advances in clinical chemistry最新文献

Organisms as well as pathogens require several transition metals including iron, copper, zinc, manganese, nickel and cobalt, for genetic replication and other cellular functions. Of these, iron is vital and plays a key role in DNA replication, transcription, synthesis of cofactors and other essential enzymes. During infection, iron deprivation, particularly sequestration thereof, represents a unique response against pathogen attack. The host sequesters ferrous (Fe²⁺) and ferric (Fe³⁺) iron via lactoferrin binding at mucosal surfaces, transferrin in blood and tissue and ferritin in blood and cytoplasm. Despite this protective mechanism, pathogens can be resilient in obtaining iron. For example, hemolytic protozoan parasites can obtain iron from heme by rupturing red blood cells. Furthermore, earlier pathogens, driven from active to inactive infections by iron deprivation, could now acquire sufficient iron to enable reactivation resulting in chronic inflammation, oxidative stress to organs and/or circulatory hypertension potentially leading to death. This review discusses the impact of hemolytic protozoan parasite infection in reactivation of latent iron-deprived pathogen infections thus explaining two puzzling pregnancy disorders, pre-eclampsia (PE) and eclampsia. The unknown causations of both disorders have created centuries of confusion and killed millions of women worldwide. Furthermore, reduction-oxidation reactions with iron promote additional oxidative stress damage to vital organs, particularly the kidneys, a common symptom in PE and eclampsia.

Malaria remains a significant global health issue, especially in tropical and subtropical regions. Although Egypt attained malaria-free status in 2024, countries like Eritrea, Ethiopia, Ghana, Kenya, Nigeria, Somalia, Sri Lanka, Sudan, and Yemen are still considered "High Burden High Impact" zones. Malaria causes over 435,000 fatalities annually and places billions more at risk. Unfortunately, treatment resistance, atypical symptomology, analytical sensitivity, and the specificity of conventional detection methods have made diagnosis challenging. To mitigate the large reservoir of malaria parasites in disease hotspots, a more strategic non-invasive diagnostic tool with improved monitoring, multiplex capability and analytical performance is required. Fortunately, the advent of novel biosensor technology that uses advanced nanotechnology design and biochemical approaches provides rapid, sensitive, and cost-effective alternatives. Furthermore, these user-friendly devices require minimal technical expertise and are ideal at the point of care, especially in remote and resource-limited settings. Herein, we examine current and emerging diagnostic tools and evaluate their potential to revolutionize malaria control and eradication efforts worldwide.

Endometriosis represents a diverse disease characterized by three distinct phenotypes: superficial peritoneal lesions, ovarian endometriomas, and deep infiltrating endometriosis. The most widely accepted pathophysiological hypothesis for endometriosis is rooted in retrograde menstruation, a phenomenon observed in most patients. Endometriosis is closely linked to infertility, but having endometriosis does not necessarily imply infertility. The disease can impact fertility through various mechanisms affecting the pelvic cavity, ovaries, and the uterus itself. MicroRNAs (miRNAs) indeed represent a fascinating and essential component of the regulatory machinery within cells. Discovered in the early 1990s, miRNAs have since been identified as critical players in gene expression control. Unfortunately, ovarian endometrioma is a common gynecologic disorder for which specific serum markers are currently lacking. Some have examined urocortin for its ability to differentiate endometriomas from other benign ovarian cysts. Another potential marker, Cancer Antigen 125 (CA-125) is a well-established indicator for epithelial cell ovarian cancer and its levels can be elevated in conditions such as endometriosis. CA-125 is derived from coelomic epithelia, including the endometrium, fallopian tube, ovary, and peritoneum. In this review we examine the pathophysiologic basis for endometriosis and highlight potential markers to more fully characterize the underlying biochemical processes linked to this multifaceted disease state.

Metabolic syndrome is a group of cardio-metabolic dysfunctions characterized by increased fasting blood glucose, blood pressure, waist circumference, triglycerides, and decreased high-density lipoprotein cholesterol. Globally, the prevalence of metabolic syndrome ranged from 12.5-31.4 %, among which 5-7 % were young adults. Environmental factors, nutrition, and genetic and epigenetic predispositions are thought to interact intricately to cause metabolic disease. MicroRNAs are short, small non-coding RNAs that attach to the target coding sequences and untranslated genomic regions in many cell types, thereby post-transcriptionally suppressing gene expression. The human genome contains around 2000 microRNAs many of which appear linked to a numerous biologic and pathophysiologic processes, such as inflammatory response, angiogenesis, and glucose homeostasis. Many human disorders, including obesity, type 2 diabetes mellitus, and cardiovascular disorders, have been linked to deregulated microRNA expression. More recently, the identification of extracellular microRNAs has highlighted their potential as markers of disease and endocrine signaling molecules. This review provides an overview of microRNA biogenesis and its function in insulin signaling, adipogenesis, biology of pancreatic β-cell, and metabolism. We review current research on microRNAs linked to vascular diabetic complications and metabolic diseases, with a focus on their diagnostic and therapeutic potential.

Heavy metal toxicity poses significant risks to environmental and human health, necessitating advanced analytical and integrative approaches for assessment and mitigation. Herein we review the use of high-resolution metabolomics, ultra-high-performance liquid chromatography-mass spectrometry (UHPLC-MS), and Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR-MS) to identify metabolic disruptions associated with heavy metal exposure. NMR, due to a non-destructive nature and ability to provide quantitative and structural information, has emerged as a vital tool in identifying biomarkers and elucidating metabolic disruptions caused by heavy metals. Integrating genomics, transcriptomics, proteomics, and lipidomics with metabolomics has significantly enhanced the understanding of gene-environment interactions. Systems biology and computational modeling bridge experimental data with predictive insights, simulating complex interactions and identifying intervention points. Furthermore, this chapter explores advanced instrumentation and the role of interdisciplinary collaboration as metabolomics, enriched by NMR and multi-omics integration, holds the potential to manage the heavy metal toxicity, paving the way for precision medicine and environmental resilience.

Diabetes mellitus is a chronic condition caused by high blood glucose resulting from insufficient insulin production or cellular resistance to insulin action or both. It is one of the fastest-growing public health concerns worldwide. Development of long-term nephropathy, retinopathy, neuropathy, and cardiovascular disease are some of the complications commonly associated with poor blood glycemic control. Type 2 diabetes mellitus (T2DM), the most prevalent type of diabetes, accounts for around 95 % of all cases globally. Although middle-aged or older adults are more likely to develop T2DM, its prevalence has grown in children and young people due to increased obesity, sedentary lifestyle and poor nutrition. Furthermore, it is believed that more than 50 % of cases go undiagnosed annually. Routine screening is essential to ensure early detection and reduce risk of life-threatening complications. Herein, we review traditional biomarkers and highlight the ongoing pursuit of novel and efficacious biomarkers driven by the objective of achieving early, precise and prompt diagnoses. It is widely acknowledged that individual biomarkers will inevitably have certain limitations necessitating the need for integrating multiple markers in screening.

Blood microsampling has demonstrated clinical utility for applications in the fields of newborn screening, therapeutic drug monitoring (TDM) of immunosuppressive drugs, and for viral detection. However, for cancer diagnostics, including early diagnosis, disease recurrence or TDM, use of blood microsampling technology is still in its infancy. Nonetheless, rapid innovation in microsampling device design coupled with proof of principle studies suggests high enthusiasm for the future integration of blood microsampling for clinical cancer applications. In this review we discuss the opportunities and challenges of using microsampling for biospecimen collection and analysis, including the stability of biomarkers using dried blood spots as this is crucial in applications relying on self-collected specimens. We highlight current research in the 'omics' biomarker field with respect to cancer diagnostics, covering applications of microsampling with proteomics, metabolomics, lipidomics, glycomics, genomics and epigenetics. Although the landscape of blood microsampling is still evolving, the potential of this technology to provide a promising solution to some of the challenges in biospecimen collection and cancer diagnostics makes it a rapidly developing and innovative research area.