The use of archival formalin-fixed paraffin-embedded (FFPE) tissue samples for biochemical analyses is problematic because of the formation of a Schiff base, leading to low protein and metabolite yields during analytical extractions. Here, we overcome this issue using a unified protocol on FFPE tissue for metabolomics and proteomics analyses. Using 20 mg of wet mass tissue, this protocol consistently extracted more than 50 metabolites (across 11 classes of metabolites) and over 900 proteins.
View Article and Find Full Text PDFDiabetic wounds are hard-to-heal due to complex multifactorial dysregulation within the micro-environment, necessitating the development of novel regenerative approaches to stimulate healing. This study investigated whether the combined therapeutic application of two novel cellular tissue products, namely a decellularized collagen-rich amniotic membrane (AmR) and growth factor-rich umbilical cord blood serum (UCBS) could have a positive synergistic effect on long-term healing outcomes by stimulating both superficial wound closure and wound bed regeneration. Full thickness excisional wounds were induced on obese diabetic mice (B6.
View Article and Find Full Text PDFMyalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating chronic condition that is characterized by unresolved fatigue, post-exertion symptom exacerbation (PESE), cognitive dysfunction, orthostatic intolerance, and other symptoms. ME/CFS lacks established clinical biomarkers and requires further elucidation of disease mechanisms. A growing number of studies demonstrate signs of hematological and cardiovascular pathology in ME/CFS cohorts, including hyperactivated platelets, endothelial dysfunction, vascular dysregulation, and anomalous clotting processes.
View Article and Find Full Text PDFUnlabelled: Coxsackievirus B3 (CVB3) encodes proteinases that are essential for processing of the translated viral polyprotein. Viral proteinases also target host proteins to manipulate cellular processes and evade innate antiviral responses to promote replication and infection. While some host protein substrates of the CVB3 3C and 2A cysteine proteinases have been identified, the full repertoire of targets is not known.
View Article and Find Full Text PDFSugarcane is an economically important crop plant across the globe as it is the primary source of sugar and biofuel. Its growth and development are greatly influenced by water availability; therefore, in periods of water scarcity, yields are severely compromised. Small Ubiquitin-Like Modifier (SUMO) proteases play an important role in stress responses by regulating the SUMO-related post-translational modification of proteins.
View Article and Find Full Text PDFViruses have evolved diverse strategies to evade the host innate immune response and promote infection. The retinoic acid-inducible gene I (RIG-I)-like receptors RIG-I and MDA5 are antiviral factors that sense viral RNA and trigger downstream signal via mitochondrial antiviral-signaling protein (MAVS) to activate type I interferon expression. 14-3-3ε is a key component of the RIG-I translocon complex that interacts with MAVS at the mitochondrial membrane; however, the exact role of 14-3-3ε in this pathway is not well understood.
View Article and Find Full Text PDFIn this paper we test a long-held assumption regarding Otago, New Zealand, goldfields life and death- that scurvy was a ubiquitous and persistent cause of misery and death among the goldminers. We will also explore a parallel argument that the Chinese market gardeners played a large role in stamping out the disease in the goldfields. Through the interrogation of various archival medical primary sources, we show that scurvy was indeed a terrible scourge in the Otago goldfields, but only during the initial rushes into new regions.
View Article and Find Full Text PDFObjectives: We test the hypothesis that the condition(s) leading to the development of cribra orbitalia at Con Co Ngua, an early seventh millennium sedentary foraging community in Vietnam, effectively reduced the resilience of the population to subsequent health/disease impacts. An assessment of both the implications and potential etiology of cribra orbitalia in this specific population is carried out.
Methods: The effective sample included 141 adults aged ≥15 years (53 females, 71 males, and 17 unknown sex) and 15 pre-adults aged ≤14 years.
Am J Biol Anthropol
June 2023
Weighted threshold diagnostic criteria approaches have emerged for diseases that involve skeletal/bony tissue that are readily diagnosed in the field of paleopathology such as Vitamin C deficiency (scurvy), Vitamin D deficiency (rickets) and treponemal disease. These criteria differ from traditional differential diagnosis in that they involve standardized inclusion criteria based on the lesion's specificity to the disease. Here I discuss the limitations and benefits of threshold criteria.
View Article and Find Full Text PDFClimate change is an indisputable threat to human health, especially for societies already confronted with rising social inequality, political and economic uncertainty, and a cascade of concurrent environmental challenges. Archaeological data about past climate and environment provide an important source of evidence about the potential challenges humans face and the long-term outcomes of alternative short-term adaptive strategies. Evidence from well-dated archaeological human skeletons and mummified remains speaks directly to patterns of human health over time through changing circumstances.
View Article and Find Full Text PDFViruses have evolved mechanisms to modulate cellular pathways to facilitate infection. One such pathway is the formation of stress granules (SG), which are ribonucleoprotein complexes that assemble during translation inhibition following cellular stress. Inhibition of SG assembly has been observed under numerous virus infections across species, suggesting a conserved fundamental viral strategy.
View Article and Find Full Text PDFFor more than two centuries, lack of sunlight has been understood to cause vitamin D deficiency and documented as a primary cause of rickets. As such, evidence of rickets in the archeological record has been used as a proxy for vitamin D status in past individuals and populations. In the last decade, a clinical global consensus has emerged wherein it is recognized that dietary calcium deficiency also plays a role in the manifestation of rickets and classic skeletal deformities may not form if dietary calcium is normal even if vitamin D is deficient.
View Article and Find Full Text PDFBackground: Post-acute sequelae of COVID-19 (PASC), also now known as long COVID, has become a major global health and economic burden. Previously, we provided evidence that there is a significant insoluble fibrin amyloid microclot load in the circulation of individuals with long COVID, and that these microclots entrap a substantial number of inflammatory molecules, including those that might prevent clot breakdown. Scientifically, the most challenging aspect of this debilitating condition is that traditional pathology tests such as a serum CRP (C-reactive protein) may not show any significant abnormal inflammatory markers, albeit these tests measure only the soluble inflammatory molecules.
View Article and Find Full Text PDFThe prevailing view regarding the evolution of medicine is that the emergence of settled agricultural societies around 10,000 years ago (the Neolithic Revolution) gave rise to a host of health problems that had previously been unknown among non-sedentary foraging populations, stimulating the first major innovations in prehistoric medical practices. Such changes included the development of more advanced surgical procedures, with the oldest known indication of an 'operation' formerly thought to have consisted of the skeletal remains of a European Neolithic farmer (found in Buthiers-Boulancourt, France) whose left forearm had been surgically removed and then partially healed. Dating to around 7,000 years ago, this accepted case of amputation would have required comprehensive knowledge of human anatomy and considerable technical skill, and has thus been viewed as the earliest evidence of a complex medical act.
View Article and Find Full Text PDFACS Appl Mater Interfaces
January 2022
The development of low-cost, non-toxic, scalable antimicrobial textiles is needed to address the spread of deadly pathogens. Here, we report a polysiloxane textile coating that possesses two modes of antimicrobial inactivation, passive contact inactivation through amine/imine functionalities and active photodynamic inactivation through the generation of reactive oxygen species (ROS). This material can be coated and cross-linked onto natural and synthetic textiles through a simple soak procedure, followed by UV cure to afford materials exhibiting no aqueous leaching and only minimal leaching in organic solvents.
View Article and Find Full Text PDFThe main viral protease (3CL) is indispensable for SARS-CoV-2 replication. We delineate the human protein substrate landscape of 3CL by TAILS substrate-targeted N-terminomics. We identify more than 100 substrates in human lung and kidney cells supported by analyses of SARS-CoV-2-infected cells.
View Article and Find Full Text PDFBackground: Severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2)-induced infection, the cause of coronavirus disease 2019 (COVID-19), is characterized by acute clinical pathologies, including various coagulopathies that may be accompanied by hypercoagulation and platelet hyperactivation. Recently, a new COVID-19 phenotype has been noted in patients after they have ostensibly recovered from acute COVID-19 symptoms. This new syndrome is commonly termed Long COVID/Post-Acute Sequelae of COVID-19 (PASC).
View Article and Find Full Text PDFThe family comprises small non-enveloped viruses with positive-sense RNA genomes of 8.6-9.6 kb.
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