Bone marrow aplasia is a common feature in acute myeloid leukemia (AML) patients during their remission induction treatment, and is associated with potential complications such as bleeding, infection and anemia. Frequent platelet and red cell transfusions are administered to prevent and treat these complications. However, platelet counts are poorly associated with bleeding events in this population. Therefore, plasma protein levels could add valuable insights to improve our understanding of the patient's health state. In this study, we aimed to delineate the plasma proteome, including inflammatory pathways, hemostatic and immune components, of AML patients during treatment with intensive transfusion support. We employed unbiased mass spectrometry (MS)-based proteomics on longitudinal plasma samples from 10 AML patients during intensive-transfusion treatment phase with healthy individuals as baseline control. A total of 450 proteins were quantified in plasma samples from AML patients and healthy controls. Alteration in proteins levels were mainly observed for proteins involved in inflammation (e.g. SAA1 and CRP), and complement (e.g. C9 and MASP2) when comparing AML versus healthy individuals. Correlation analysis revealed additional affected protein dynamics, including proteins associated with coagulation cascade, endopeptidase inhibitors activity and lipoprotein remodeling. The plasma proteome from AML patients during intensive treatment shows a disbalance in inflammation, endopeptidase inhibitors activity, lipoprotein remodeling, coagulation and complement. These effects and potential associations with bleeding risk will be further studied in a bigger cohort.
Atheroma is a serious atherosclerotic lesion related to plaque rupture, thrombosis, and ischemic disease. To clarify the pathogenesis of human atheroma, particularly the formation of the liponecrotic tissue in the necrotic core, the distribution of connective tissue fibers, such as collagen and elastic fibers, and related substances was investigated in this study. Atherosclerotic lesions in human coronary arteries were classified into three categories: pathologic intimal thickening (PIT), atheroma with lipid core (ALC), and atheroma with necrotic core (ANC). PIT and ALC consisted of the lipid pool and the lipid core, respectively. The necrotic core of ANC was composed of a lipid core-like region and liponecrotic tissue containing amorphous materials and lacking cells and connective tissue fibers. The distribution of collagen type I, elastin, C-terminal crosslinked telopeptide of collagen type I (CTX-I), and cathepsin K (CatK) was investigated through immunohistochemistry. CTX-I is a fragmented peptide consisting of the C-terminal region of collagen type I that is generated by CatK. The distribution of denatured and unfolded collagen chains was also investigated through collagen hybridizing peptide staining. Collagen type I, denatured and unfolded collagen chains, and elastin were positively stained in the PIT, ALC, and lipid core-like region of ANC. However, they were negatively stained in the liponecrotic tissue of ANC. CTX-I and CatK were positively stained in all four regions, and their grade of staining appeared to show a positive relationship. Both CTX-I and CatK demonstrated higher staining grades in the liponecrotic tissue. These findings suggested that pre-existing collagen type I was severely degraded by CatK, resulting in the production of CTX-I in the liponecrotic tissue, and that pre-existing elastin was also degraded in this region. CatK was mainly found in macrophage foam cells, many of which were localized within and around the liponecrotic tissue. This study suggests that the liponecrotic tissue in the necrotic core of human atheroma is formed by severe degradation of pre-existing connective tissue fibers and consequent collapse of tissue structure. This degradation is likely caused by proteolytic enzymes, such as CatK, secreted by macrophage foam cells.
Antiretroviral therapy (ART) has significantly improved the prognosis for people living with human immunodeficiency virus (PLWH). However, alterations in the gut microbiota of PLWH affect their metabolic environment and may contribute to chronic inflammation and premature aging, despite effective ART. Given that inflammation in the body have been shown to be risk factors for age-related diseases, elucidating changes in the gut microbiota and metabolic levels over time in individuals would be for understanding the dynamics in the body that lead to disease development. The study assessed changes in blood markers, gut microbiota, and metabolic environment of PLWH on ART for four years, with participants divided into two groups based on median CD4 cell count (580/µL). The high-CD4 group was more obese than the low-CD4 group, but there was no significant difference in comorbidities, such as diabetes, hypertension, and dyslipidemia. An investigation of the alterations in gut microbiota over a 4-year period revealed a reduction in specific groups of bacteria that produce short-chain fatty acids (SCFAs) and an increase in the occurrence of Enterobacteriaceae. In addition, a decline in bacterial thiamine synthesis was predicted, and a decreased abundance of the Ruminococcus gauvreauii group, which relies on supplementation with thiamine from symbiotic bacteria, was observed. The abundance of Collinsella and Catenibacterium at baseline was positively correlated with the predicted number of thiamine-synthesizing pathway. The presence of Catenibacterium at follow-up was inversely correlated with the rate of increase in plasma levels of lipopolysaccharide-binding protein, an indicator of a leaky gut. In terms of assessing the diversity of gut microbiota, a trend towards an increase in opportunistic bacteria with different genetic distances was observed in the high-CD4 group at follow-up. These observations suggested that, despite effective ART, the thiamine-deficient environment in the gut continues to reduce thiamine-requiring bacteria, such as certain SCFA-producing bacteria. As a result, secondary effects, such as proliferation of opportunistic bacteria and chronic inflammation associated with increased intestinal permeability, proceed in PLWH. Thus, certain essential nutrient deficiencies for gut metabolic environment may disrupt the symbiotic relationship between gut bacteria and increase the risk of developing inflammatory diseases.
Breast cancer (BC) is the primary cause of cancer-related deaths among women. BH3 only proteins expression profile in BC has been linked to chemotherapy and treatment outcomes. Clinical biomarkers provide insights into disease progression. Therefore, we systematically investigated the prognostic significance of proapoptotic Bcl-2 Homology Domain 3 (BH3) only proteins in Disease-Free Survival (DFS) and Overall Survival (OS) among BC patients. We explored four databases, screening titles, abstracts, and full articles based on predefined criteria. The quality of cohort studies and randomized clinical trials were assessed. Data of BH3-only gene and proteins’ expression were extracted and meta-analysis using random effects model was performed. Of the 3541 studies identified, nine studies met inclusion criteria. The meta-analysis revealed that the BH3-only protein-positive group had a higher chance of 5-year DFS risk ratio (RR = 1.17, 95
Delirium, characterized by a sudden onset of neuropsychiatric symptoms, is a highly prevalent syndrome whose diagnosis is defined solely through clinical evaluation. Due to the often challenging reliability of assessments, especially in non-cooperative patients, there is a growing emphasis on exploring new reliable biomarkers, such as Neuron-Specific Enolase (NSE). NSE, an enzyme primarily found in neuronal and neuroendocrine tissues, has been clinically used to assess the prognosis of patients who have experienced traumatic or hypoxic brain injuries. Thus, the primary purpose of the present review is to examine the literature to determine whether NSE is applicable for diagnosis and/or prognosis of patients with delirium. Literature was searched using Pubmed, Lilacs and Scielo databases, and all published reports identified as potentially relevant were independently assessed by each reviewer. All relevant original studies were included and independent extraction of articles was performed by three authors using predefined data fields. Twenty one studies (2,311 patients) satisfied the entry criteria, among which only eight suggest a possible association between NSE and delirium, particularly in intensive care settings, and only one correlate NSE with delirium prognosis. Also, significant heterogeneity was observed among studies, varying across study design, setting, and methodologies. Furthermore, the majority of the selected studies presented severe methodological limitations, particularly small samples. In conclusion, this systematic review underscores the need for further research with larger, standardized studies to establish the reliability and validity of NSE as a diagnostic and prognostic tool for delirium. The current evidence does not sufficiently support its routine clinical application in assessing patients with delirium.
Background Kidney stones, or renal nephrolithiasis, are common and dangerous, increasing the risk of chronic kidney disease. Dietary manipulation is essential for the prevention and recurrence of kidney stones. Research into nutrition and kidney stones lacks library analysis, making it difficult to identify new trends. This bibliometric study was conducted to explore the current landscape of research on nutrition and kidney stones worldwide. This paper also emphasizes significant research trends in this area over the past two decades, aiming to assist researchers in understanding the current research status and identifying potential future directions. Methods The scholarly literature pertaining to diet and kidney stones was systematically explored utilizing SciVerse Scopus to identify pertinent research articles released from 2003 to 2022. The examination encompassed an assessment of publication patterns, key contributors, focal areas of research, prevalent themes, influential articles, and emerging research avenues. Following data extraction to Excel, analyses, including frequencies, percentages, and linear regression, were conducted. Visual exploration was facilitated through the use of the VOSviewer program version 1.6.19. Results Between 2003 and 2022, 697 publications on nutrition and kidney stones were identified. There were 478 original articles (68.58%), 120 reviews (17.22%) and 99 other types of publications (14.20%). The United States is the most productive country, with significant growth in research in the fields of nutrition and kidney stones. The United States has demonstrated the strongest partnerships between researchers’ networks from various countries. Cluster analysis revealed three major research themes: sex differences in kidney stone disease, the correlation between increased dietary acid consumption and calcium oxide kidney stones, and nephrolithiasis associated with a ketogenic diet. Conclusions This study offers a thorough examination of nutrition and kidney stone research, encompassing key research domains, collaborative networks, and emerging patterns. The findings can aid researchers in gaining insight into the present landscape of the discipline and determining future research directions.
The incidence of brain diseases in humans is increasing as we experience a worldwide ageing of the population. Treatment for such diseases is still only symptomatic as there are almost no disease-modifying therapies available. Further, since treatment often starts when symptoms appear which is only at a late stage of pathology, we need treatments that will create new cells or restore function to still living cells. Cell transplant therapy, where neuronal progenitor cells derived from stem cells are transplanted to the brain, has seen experimental success. And though there has been some clinical progress, there is still no available therapy. While through the years brain research has focused on neurons, it is now shifting to the so-called support cells of the brain, glia. In neurodegenerative diseases and stroke, glia play roles in the pathogenesis of disease. Therefore, replacing them or enhancing their functions to ultimately save or restore neurons is a new avenue of research that has gained traction in recent years. In this review, we present the current state-of-the-art on transplantation of glia cells, feasibility of this as a therapy, and upcoming directions in the field.
Background Late-stage human immunodeficiency virus (HIV) infection is typically characterized by low CD4 + T-cell count. We previously showed that profound changes in the monocyte turnover (MTO) rate in rhesus macaques infected by the simian immunodeficiency virus (SIV) outperforms declining CD4 + T-cell counts in predicting rapid health decline associated with progression to terminal disease. High MTO is associated with increased tissue macrophage death. However, MTO analysis is complex and not directly applicable to humans. Methods We explored blood-available biomarkers associated with MTO using comprehensive immune cell profiling via flow cytometry, blood cell count and chemistry, and ELISA. Results Plasma galectin-9 was identified as the most highly correlated marker with MTO. This correlation remained statistically significant during acute, chronic, and late-stage infections caused by three different SIV strains tested. In addition, the galectin-9 level also predicted decline in animal health, requiring medical cull. The correlation between MTO and galectin-9 was maintained even in uninfected animals showing variable MTO. Conclusions These findings support the exploration of galectin-9 as a surrogate biomarker of MTO for non-invasive monitoring of disease progression (e.g. HIV) that may also be applicable in humans and as a potential indicator of tissue macrophages apoptosis.
Background Insulin resistance is a major pathogenic factor that plays a crucial role in the development of metabolic syndrome and has been proposed as one of its underlying causes. Most diagnostic criteria for metabolic syndrome do not directly include insulin resistance. Furthermore, research on insulin resistance continues to provide information on the development and treatment of metabolic syndromes and related health conditions. Therefore, this bibliometric analysis aimed to investigate the current research status and identify possible future research hotspots in the area of metabolic syndrome and insulin resistance by analyzing Scopus-based studies. Methods To collect published data on metabolic syndrome and insulin resistance, this study used the Scopus database as its data source without a particular starting date but including records up to December 31, 2022. The gathered documents were then exported to VOSviewer v.1.6.18 to analyze and visualize country collaborations and identify research areas of high interest. Results The study presents an overview of 1932 records between 1988 and 2022, focusing on metabolic syndrome and insulin resistance. Of these records, 77.33% were original journal articles, while 13.30% were review articles. Additionally, 9.35% of the documents fall under other types of publication, including letters, notes, and editorials. The United States came out on top with 463 items, accounting for 23.96% of the contributions in this field, followed by Japan in second place with 119 items (6.16%). China ( n = 113, 5.85%) and the United Kingdom ( n = 113, 5.85%) ranked third. Most publications on metabolic syndrome and insulin resistance focus on key terms related to the pathogenesis of insulin resistance syndrome, the use of waist circumference as a crucial clinical indicator to evaluate the risk of metabolic syndrome, and the association between metabolic syndrome and oxidative stress and a pro-inflammatory state. Conclusions This study presents the first bibliometric analysis of publications focusing on metabolic syndrome and insulin resistance. The findings of this study offer a comprehensive global perspective on the research carried out on metabolic syndrome and insulin resistance and can be an invaluable source for future research.
Background:Many tumors contain hypoxic microenvironments caused by inefficient tumor vascularization. Hypoxic tumors have been shown to resist conventional cancer therapies. Hypoxic cancer cells rely on glucose to meet their energetic and anabolic needs to fuel uncontrolled proliferation and metastasis. This glucose dependency is linked to a metabolic shift in response to hypoxic conditions. Methods:To leverage the glucose dependency of hypoxic tumor cells, we assessed the effects of a mild reduction in systemic glucose by controlling both dietary carbohydrates with a ketogenic diet and endogenous glucose production by using metformin on two mouse models of triple-negative breast cancer (TNBC). Results:Here, we showed that animals with TNBC treated with the combination regimen of ketogenic diet and metformin (a) had their tumor burden lowered by two-thirds, (b) displayed 38% slower tumor growth, and (c) showed 36% longer latency, compared to the animals treated with a ketogenic diet or metformin alone. As a result, lowering systemic glucose by this combined dietary and pharmacologic approach improved overall survival in our mouse TNBC models by 31 days, approximately equivalent to 3 years of life extension in human terms. Conclusion:This preclinical study demonstrates that reducing systemic glucose by combining a ketogenic diet and metformin significantly inhibits tumor proliferation and increases overall survival. Our findings suggest a possible treatment for a broad range of hypoxic and glycolytic tumor types that can augment existing treatment options to improve patient outcomes.
Eosinophilic esophagitis (EoE) is a chronic inflammatory condition characterized by an intense infiltration of eosinophils into the esophageal epithelium. When not adequately controlled, eosinophilic inflammation can lead to changes in components of the extracellular matrix (ECM) of the lamina propria. Particularly, alterations to the collagen fiber matrix can lead to lamina propria fibrosis (LPF), which plays an important role in the fibrostenotic complications of EoE. Current approaches to assess LPF in EoE are prone to inter-observer inconsistencies and provide limited insight into the structural remodeling of the ECM. An objective approach to quantify LPF can eliminate inter-observer inconsistencies and provide novel insights into the fibrotic transformation of the lamina propria in EoE. Second harmonic generation (SHG) microscopy is a powerful modality for objectively quantifying disease associated alterations in ECM collagen structure that is finding increasing use for clinical research. We used SHG with morphometric analysis (SHG-MA) to characterize lamina propria collagen fibers and ECM porosity in esophageal biopsies collected from children with active EoE (n = 11), inactive EoE (n = 11), and non-EoE (n = 11). The collagen fiber width quantified by SHG-MA correlated positively with peak eosinophil count (r = 0.65, p < 0.005) and histopathologist scoring of LPF (r = 0.52, p < 0.005) in the esophageal biopsies. Patients with active EoE had a significant enlargement of ECM pores compared to inactive EoE and non-EoE (p < 0.005), with the mean pore area correlating positively with EoE activity (r = 0.76, p < 0.005) and LPF severity (r = 0.65, p < 0.005). These results indicate that SHG-MA can be utilized to objectively characterize and provide novel insights into lamina propria ECM structural remodeling in children with EoE, which could aid in monitoring disease progression.
Background:Tissue engineering is a multidisciplinary field that combines principles from cell biology, bioengineering, material sciences, medicine and surgery to create functional and viable bioproducts that can be used to repair or replace damaged or diseased tissues in the human body. The complexity of tissue engineering can affect the prospects of efficiently translating scientific discoveries in the field into scalable clinical approaches that could benefit patients. Organizational challenges may play a key role in the clinical translation of tissue engineering for the benefit of patients.Methods:To gain insight into the organizational aspects of tissue engineering that may create impediments to efficient clinical translation, we conducted a retrospective qualitative case study of one tissue engineering multi-site translational project on knee cartilage engineered tissue grafts. We collected qualitative data using a set of different methods: semi-structured interviews, documentary research and audio-visual content analysis.Results:Our study identified various challenges associated to first-in-human trials in tissue engineering particularly related to: logistics and communication; research participant recruitment; clinician and medical student participation; study management; and regulation.Conclusions:While not directly generalizable to other types of advanced therapies or to regenerative medicine in general, our results offer valuable insights into organizational barriers that may prevent efficient clinical translation in the field of tissue engineering.
Abstract Rett syndrome (OMIM 312750) is a rare neurodevelopmental disorder caused by de novo mutations in the Methyl-CpG Binding Protein 2 (MeCP2) gene located on the X-chromosome, typically affecting girls. Rett syndrome symptoms, characterized by microcephaly and lack of motor coordination, first appear between 6 to 18 months of age. The disease continues to progress until adulthood at which point it reaches a stationary phase. Currently, available therapy for Rett Syndrome is only symptomatic. More than 800 mutations causing Rett syndrome have been described, the most common being T158M (9% prevalence) located in the Methyl-Binding Domain (MBD) of MeCP2. Due to its importance for DNA binding through recognition of methylated CpG, mutations in the MBD have a significant impact on the stability and function of MeCP2. MeCP2 is a nuclear protein and accumulates in liquid–liquid phase condensates visualized as speckles in NIH3T3 cells by microscopy. This speckled pattern is lost with MeCP2 mutations in the MBD such as T158M. We developed a high content phenotypic assay, detecting fluorescent MeCP2 speckles in NIH3T3 cells. The assay allows the identification of small molecules that stabilize MeCP2-T158M and phenotypically rescue speckle formation. To validate the assay, a collection of 3572 drugs was screened, including FDA-approved drugs, compounds in clinical trials and biologically annotated tool compounds. 18 hits showed at least 25% rescue of speckles in the mutant cell line while not affecting wild-type MeCP2 speckles. Primary hits were confirmed in a dose response assay, a thermal shift assay with recombinant MeCP2 and by testing the MeCP2 expression levels. One class of identified hits represents histone deacetylase inhibitors (HDACis) showing 25% speckle rescue of mutant MeCP2 without toxicity. This screening strategy can be expanded to additional compound libraries and will support novel drug discovery.
We aimed to investigate the development of synovial fibrosis in vitro and how the fibrosis can be halted. Synovial fibrosis causes joint stiffness in arthritic diseases. The pathway of the fibrotic growth factor, transforming growth factor-beta (TGF-β), has been associated with joint pain in osteoarthritis (OA) and with the fibroid phenotype of rheumatoid arthritis (RA). This suggests that synovial fibrosis, thus accumulation of extracellular matrix (ECM) proteins, plays a role in the clinical manifestations of the diseases. Improving our understanding of fibrotic development may aid in selecting appropriate treatments and development of drugs that can target synovial fibrosis. We isolated primary fibroblast-like synoviocytes (FLS) from the synovial membrane of patients undergoing total knee replacement surgery. To investigate the development of synovial fibrosis, the FLS were cultured in a crowded in vitro model mimicking the ECM. TGF-β1 was used as the fibrotic initiator, the activin receptor-like kinase 5 inhibitor (ALK5i), the anti-fibrotic drug nintedanib, and the anti-inflammatory drug tofacitinib were used as fibrotic inhibitors. The ECM protein formation was quantified in the conditioned media using specific biomarkers of type I, III, and VI collagen formation and fibronectin turnover. The TGF-β stimulation inducted fibrogenesis by increasing the biomarkers of fibronectin turnover, type I, III, and VI collagen formation. ALK5i and nintedanib inhibited the TGF-β response across all biomarkers. Tofacitinib trended towards inhibiting TGF-β response with up to 78
SARS-CoV-2 caused an outbreak in late December 2019. It has been suggested that gut microbiota dysbiosis influences the severity, mortality, and quality of life of patients with COVID-19. So, identifying the gut microbiota pattern could be helpful to determine the prognosis of the disease, and maybe determine some potential treatment approaches. Our aim will be to compare gut microbiota patterns between patients with severe or non-severe COVID-19, and healthy controls. We will include 183 samples: 122 samples from COVID-19 patients, including 61 severe patients and 61 non-severe patients, and 61 samples from healthy controls. Total bacterial DNA will be extracted from samples and 16 S rRNA gene will be amplified through two polymerase chain reaction (PCR) stages. Fecal samples will be analyzed using a targeted metabolomics technique. The differences in each RNA or DNA expression between patients with severe COVID-19, patients with non-severe COVID-19, and controls will be compared. Also, we will assess the relationships between each DNA or RNA and the risk of COVID-19 severity, sort of clinical manifestations, and comorbidities. Concurrent medication data will be collected and patients will also be grouped based on their drug history. We hypothesize that the gut microbiota composition will be affected by the COVID-19 severity and there might be differences in terms of sex and age. The results of our study could be the backbone for further trials which might lead to the development of prognostic factors and treatment options. Further studies can also consider the limitations of the study like potential confounders and selection and recall biases.
Abstract Background Uterus tissue engineering aims to repair a dysfunctional uterus that causes infertility, e.g., after significant scarring from benign or malign resection procedures. Decellularized uterine tissue provided regenerative support in several animal models as a biocompatible natural extracellular matrix (ECM) derived scaffold after uterine damage. However, variations in decellularization protocols and species used limit conclusive evidence and translational progress. Hence, a species-independent decellularization protocol could facilitate preclinical research. Therefore, we investigated if our developed sheep uterus decellularization protocol was species-independent and effective for the significantly larger bovine uterus. We further assessed if there were any negative post transplantation immunological consequences from the metalloproteinases 2 and 9 (MMP 2, MMP 9) treatment that was used as a preconditioning treatment to significantly improve scaffold recellularization after decellularization. Methods Bovine uterus was decellularized using sodium deoxycholate, and the remaining ECM was quantitatively assessed for DNA, protein, and ECM components. The morphology and physical attributes were examined by immunohistochemistry, electron microscopy, and mechanical tests. Scaffold biocompatibility, bioactivity, and angiogenic properties were assessed with the chorioallantoic membrane assay (CAM) and the immune response following transplantation of MMP treated scaffolds was compared with untreated scaffolds in a rat model. The in vitro recellularization efficiency of the scaffolds was also assessed. Results The decellularization protocol was effective for bovine uterus. The MMP treatment did not negatively affect scaffold immunogenicity in vivo, while the treatment potentiated mesenchymal stem cell recellularization in vitro. Furthermore, the decellularization protocol generated biocompatible and angiogenic uterine scaffolds. Conclusion Bovine uterus was successfully decellularized using previously established protocols. These results confirm earlier findings in the sheep model and further indicate that MMP treatment may be beneficial. The results further conclude the development of a species-independent, reproducible, and biocompatible scaffold generation protocol that can provide an important element for successful translational research.
Abstract Background In recent years, there has been a noteworthy increase in research exploring the relationship between gut microbiota and bariatric surgery. This increase can be attributed to the growing recognition of the importance of gut microbiota in diverse health issues, such as obesity, and its alterations following bariatric surgery. Consequently, this study seeks to employ bibliometric analysis to show the current research landscape and identify key areas of focus for future investigations on the link between bariatric surgery and gut microbiota. Methods We conducted a comprehensive search of the Scopus database to gather literature concerning bariatric surgery and its impact on the gut microbiota. The search encompassed documents published between 2009 and 2023. To analyze the bibliometric data, we employed diverse metrics, including publication count, citation count, and evaluation of the performance of countries, institutions, and journals. Additionally, we utilized VOSviewer to visually present the findings. Results A total of 555 articles focused on the correlation between bariatric surgery and the gut microbiota. Original research articles constituted 55.32% of all publications on this topic, followed by reviews at 37.30%. The leading countries in terms of publication volume were the USA (n = 156; 28.11%), China (n = 73; 13.15%), and the UK (n = 52; 9.37%). Co-occurrence analysis highlighted three main clusters of research topics: (1) the impact of bariatric surgery on the gut microbiota composition in relation to obesity remission, (2) the relationship between glucose metabolism, circulating bile acids, gut hormones, and gut microbiome remodeling, and (3) the connections between alterations in the gut microbiota and insulin resistance. Conclusions Ongoing research has investigated the connection between bariatric surgery and the gut microbiota, providing new perspectives on metabolic improvements after surgery. Further studies are necessary to comprehensively grasp how bariatric procedures influence the gut microbiota and to formulate precise interventions aimed at optimizing the health advantages of surgery.
Background: Pancreatic cancer (PC) remains a significant healthcare challenge due to its aggressive nature and poor prognosis. The current gold standard that combines imaging modalities, endoscopy, and biopsies has limited diagnostic efficacy due to various shortcomings. Methods: We propose a feasibility study for the use of a bioimpedance biomarker to detect PC. The biomarker was evaluated in a double blind study on ex vivo pancreata of mice: 15 LSL-KrasG12D; LSL-p53R172H; Pdx1-Cre, 2 LSL-KrasG12D, and 9 wild type controls (Study 1). To determine if the biomarker can distinguish between PC and acute pancreatitis (AP), we challenged it with 18 cerulein-induced AP and 6 saline-injected controls (Study 2). Results: The results from Study 1 showed 100% specificity and 94% sensitivity against histopathology outcomes; for Study 2 all AP and saline-injected pancreases were diagnosed as non-cancerous. Regression analysis revealed a positive correlation between biomarker and pathologically analyzed cancer-induced fibrosis (r(24)= 0.73 (p<0.001)). Conclusion: These findings demonstrate the potential of this bioimpedance biomarker as a diagnostic tool for PC.
AbstractParkinson’s disease (PD) is a prevalent neurodegenerative disorder affecting millions of elderly individuals worldwide. Clinically, PD is diagnosed based on the presentation of motoric symptoms. Other methods such as F-DOPA PET scan or α-Synuclein detection from the cerebral spinal fluid are either too expensive or invasive for routine use. Omics platforms such as transcriptomics, proteomics, and metabolomics may identify PD biomarkers from blood, which can reduce cost and increase efficiency. However, there are many biological moieties being measured and issues with false positives/negatives. It is also unknown which omics platform offers most useful information. Therefore, it is important to assess the reliability of these omics studies. Here, we shortlisted and analysed nearly 80 published reports across transcriptomics, proteomics and metabolomics in search of overlapping blood-based biomarkers for PD. The top biomarkers were reported across 29%, 42% and 12.5% of shortlisted papers in transcriptomics, proteomics and metabolomics respectively. These percentages increased to 42%, 60% and 50% accordingly when studies were grouped by specific blood subtypes for analysis, demonstrating the need for test kits to be blood-subtype specific. Following systematic analyses, we propose six novel PD biomarkers: two mRNAs (Whole blood, WB) – Arg1 and SNCA, two proteins (Plasma EV) – SNCA and APOA1, and two metabolites (WB) – 8-OHdG and uric acid for further validation. While these proposed biomarkers are useful, they are also snapshots, representing subsets of larger pathways of origin where the different omics levels corroborate. Indeed, identifying the interconnections across different biological layers can strengthen contextual reasoning, which in turn, would give rise to better quality biomarkers. Knowledge integration across the omics spectrum revealed consistent aberrations on the same neuroinflammation pathway, showcasing the value of integrative (i)-omics agreements for increasing confidence of biomarker selection. We believe that our findings could pave the way for identifying reproducible PD biomarkers, with potential for clinical deployment. Graphical Abstract Six Proposed blood-based biomarkers. Seventy-nine publications across transcriptomics, proteomics and metabolomics were shortlisted and analysed for reported biomarkers. The proposed biomarkers are SNCA, APOA1, Arg1, 8-OHdG and Uric acid.
Abstract Background The COVID-19 pandemic and the consequences of safety measures, such as lockdowns, have impacted not only the physical health of individuals but also their lifestyle, psychosocial health, and mental health. In this analysis, we aimed to explore the effect of the COVID-19 pandemic on lifestyle, eating habits, and sleep quality in the Palestinian population. Furthermore, the current study aimed to determine the factors associated with poor sleep. Methods The study was carried out between November 2021 and February 2022 after a long lockdown. We adopted a cross-sectional design to achieve the objectives of this study. The questionnaire included information on sociodemographic characteristics and other characteristics. In addition, questions related to lifestyle changes and items related to changes in the consumption of certain types of food were included. Furthermore, in the present study, two scales were used to assess sleep quality: the Epworth Sleepiness Scale (ESS) and the Pittsburgh Sleep Quality Index (PSQI). Results A total of 978 participants were included in this study; 508 (51.9%) were women, and 465 (47.5%) were aged between 17 and 30 years. 41% of the participants added one meal or more, and almost 43% skipped one meal or more. A total of 39.2% believed that their habits worsened as a result of the COVID-19 pandemic. A significant portion of the population increased their vitamin intake by 62.5%. In general, nuts, fast food, fried food, coffee, snacks, cans, and homemade baked foods were consumed at higher rates overall. The median ESS score, which measures general levels of daytime drowsiness, was 20.00 (18.00–22.00). Residency (p = 0.008), living status (p < 0.001), salary (p < 0.001), education level (p = 0.002), job status (p = 0.015), and vitamin intake (p < 0.001) were significantly associated with the ESS score. The PSQI score, which evaluates adult sleep patterns and quality, has a median value of 5.00. (4.00–7.00). Living status (p < 0.001), salary (p = 0.006), job status (p = 0.002), smoking status (p = 0.030), chronic diseases (p = 0.002), and vitamin use (p < 0.001) were significantly associated with the PSQI score. Only taking multivitamins was a predictor of having a lower score on both the ESS (p = 0.001) and PSQI (p < 0.001). Conclusions Our findings clearly showed that the COVID-19 pandemic has substantially affected the Palestinian population in different aspects of life. We recommend that health authorities and healthcare providers continually share knowledge and awareness about good eating habits, sleep quality, and other aspects of lifestyles.
