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The Journal of Maternal-fetal &... Dec 2023Spontaneous preterm birth (delivery before 37 completed weeks) is the single most important cause of perinatal morbidity and mortality. The rate is increasing world-wide...
Spontaneous preterm birth (delivery before 37 completed weeks) is the single most important cause of perinatal morbidity and mortality. The rate is increasing world-wide with a great disparity between low, middle and high income countries. It has been estimated that the cost of neonatal care for preterm babies is more than 4 times that of a term neonate admitted into the neonatal care. Furthermore, there are high costs associated with long-term morbidity in those who survive the neonatal period. Interventions to stop delivery once preterm labor starts are largely ineffective hence the best approach to reducing the rate and consequences is prevention. This is either primary (reducing or minimizing factors associated with preterm birth prior to and during pregnancy) or secondary - identification and amelioration (if possible) of factors in pregnancy that are associated with preterm labor. In the first category are optimizing maternal weight, promoting healthy nutrition, smoking cessation, birth spacing, avoidance of adolescent pregnancies and screening for and controlling various medical disorders as well as infections prior to pregnancy. Strategies in pregnancy, include early booking for prenatal care, screening and managing medical disorders and their complications, and identifying predisposing factors to preterm labor such as shortening of the cervix and timely instituting progesterone prophylaxis or cervical cerclage where appropriate. The use of biomarkers such as oncofetal fibronectin, placental alpha-macroglobulin-1 and IGFBP-1 where cervical screening is not available or to diagnosis PPROM would identify those that require close monitoring and allow the institution of antibiotics especially where infection is considered a predisposing factor. Irrespective of the approach to prevention, timing the administration of corticosteroids and where necessary tocolysis and magnesium sulfate are associated with an improved outcome. The role of genetics, infections and probiotics and how these emerging dimensions help in the diagnosis of preterm birth and consequently prevention are exciting and hopefully may identify sub-populations for targeted strategies.
Topics: Adolescent; Female; Humans; Infant, Newborn; Pregnancy; Early Detection of Cancer; Obstetric Labor, Premature; Placenta; Premature Birth; Uterine Cervical Neoplasms
PubMed: 36966809
DOI: 10.1080/14767058.2023.2183756 -
Frontiers in Network Physiology 2023The low-density lipoprotein related protein receptor 1 (LRP1), also known as CD91 or α-Macroglobulin-receptor, is a transmembrane receptor that interacts with more than... (Review)
Review
The low-density lipoprotein related protein receptor 1 (LRP1), also known as CD91 or α-Macroglobulin-receptor, is a transmembrane receptor that interacts with more than 40 known ligands. It plays an important biological role as receptor of morphogens, extracellular matrix molecules, cytokines, proteases, protease inhibitors and pathogens. In the CNS, it has primarily been studied as a receptor and clearance agent of pathogenic factors such as Aβ-peptide and, lately, Tau protein that is relevant for tissue homeostasis and protection against neurodegenerative processes. Recently, it was found that LRP1 expresses the Lewis-X (Lex) carbohydrate motif and is expressed in the neural stem cell compartment. The removal of from the cortical radial glia compartment generates a strong phenotype with severe motor deficits, seizures and a reduced life span. The present review discusses approaches that have been taken to address the neurodevelopmental significance of LRP1 by creating novel, lineage-specific constitutive or conditional knockout mouse lines. Deficits in the stem cell compartment may be at the root of severe CNS pathologies.
PubMed: 37383546
DOI: 10.3389/fnetp.2023.1190240 -
Frontiers in Neuroscience 2023The peripheral immune system changes in amyotrophic lateral sclerosis (ALS), but the causal relationship between the two is still controversial.
INTRODUCTION
The peripheral immune system changes in amyotrophic lateral sclerosis (ALS), but the causal relationship between the two is still controversial.
METHODS
In this study, we aimed to estimate the causal relationship between peripheral immune markers and ALS using a two-sample Mendelian randomization method. Genome-wide association study (GWAS) data on peripheral blood immune traits from European populations were used for exposure, and ALS summary statistics were used as the outcome. The causal relationship was evaluated by inverse variance weighting, MR-Egger, and weighted median methods and verified by multiple sensitivity analysis.
RESULTS
We found that the increase of one standard deviation of lymphocyte count is related to reducing ALS risk. CD3 on effector memory CD4 T cell, HLA DR CD4 T cell, effector memory CD8 T cell, terminally differentiated CD8 T cell and CD28- CD8 T cell is also a protective factor for ALS. Among the circulating immune protein, the increase of one standard deviation of α-2-macroglobulin receptor-associated protein (α-2-MRAP) and C4b showed associated with low risk of ALS, while Interleukin-21 (IL-21) increases the risk of ALS.
DISCUSSION
Our study further reveals the important role of peripheral immune activity in ALS.
PubMed: 38188028
DOI: 10.3389/fnins.2023.1269354 -
Brain, Behavior, and Immunity Jul 2023Low-grade inflammation may occur in association with several mental disorders of early adulthood, though associations with markers of chronic inflammation such as...
Associations between plasma inflammatory markers and psychotic disorder, depressive disorder and generalised anxiety disorder in early adulthood: A nested case-control study.
BACKGROUND
Low-grade inflammation may occur in association with several mental disorders of early adulthood, though associations with markers of chronic inflammation such as soluble urokinase plasminogen activator receptor (suPAR) are less well-established. We aimed to examine associations between acute and chronic inflammatory markers and mental disorders, as well as psychiatric co-morbidity, in young adults aged 24 years in the Avon Longitudinal Study of Parents and Children.
METHODS
Included were 781 participants (of 4019 who attended at age 24 years) who completed psychiatric assessments and provided plasma samples. Of these, 377 met criteria for psychotic disorder, depressive disorder or generalised anxiety disorder and 404 did not. Plasma concentrations of IFN-γ, IL-6, IL-8, IL-10, TNF-α, CRP, sVCAM1, sICAM1, suPAR and alpha-2-macroglobulin were measured using immunoassays. Logistic regression compared standardised inflammatory marker levels in cases and controls. Negative binomial regression evaluated associations between inflammatory markers and co-morbidity (number of mental disorders). Models were adjusted for sex, body mass index, cigarette smoking, cannabis use and employment status, then additionally for childhood trauma.
RESULTS
For psychotic disorder, there was evidence for associations with IL-6 (odds ratio[OR] 1.68, 95 %CI 1.20-2.34) and suPAR (OR 1.74, 95 %CI 1.17-2.58). There was weaker evidence for an association between suPAR and depressive disorder (OR 1.31, 95 %CI 1.05-1.62). There was little evidence for associations between inflammatory markers and generalised anxiety disorder. There was weak evidence for an association between suPAR and co-morbidity (β 0.10, 95 %CI 0.01-0.19). There was little evidence for additional confounding by childhood trauma.
CONCLUSIONS
There was evidence that 24-year-olds with psychotic disorder had raised plasma IL-6 and suPAR concentrations compared to controls. These findings have implications regarding the role of inflammation in mental disorders in early adulthood.
Topics: Child; Young Adult; Humans; Adult; Receptors, Urokinase Plasminogen Activator; Biomarkers; Longitudinal Studies; Case-Control Studies; Interleukin-6; Psychotic Disorders; Inflammation; Anxiety Disorders; Depressive Disorder
PubMed: 37004760
DOI: 10.1016/j.bbi.2023.03.025 -
PloS One 2023Predicting the long-term disability outcomes of multiple sclerosis (MS) cases is challenging.
BACKGROUND
Predicting the long-term disability outcomes of multiple sclerosis (MS) cases is challenging.
OBJECTIVE
We prospectively analysed our previous MS cohort with initial cerebrospinal fluid (CSF) proteomics data to reveal disability markers after 8.2±2.2 years of follow-up.
METHODS
Patients with regular follow-up visits were assigned into two groups: those with an age-related MS severity (ARMSS) score ≥5 (unfavourable course group, N = 27) and ARMSS score <5 (favourable course group, N = 67). A machine learning-based algorithm was applied to reveal candidate poor prognosis-associated initial CSF proteins, which were measured in an independent MS cohort (verification group, N = 40) by ELISA. Additionally, the correlation of initial clinical and radiological parameters with long-term disability was analysed.
RESULTS
CSF alpha-2-macroglobulin (P = 0.0015), apo-A1 (P = 0.0016), and haptoglobin (P = 0.0003) protein levels, as well as cerebral lesion load (>9 lesions) on magnetic resonance imaging, gait disturbance (P = 0.04), and bladder/bowel symptoms (P = 0.01) were significantly higher in the unfavourable course group than in the favourable course group. Optic nerve involvement evident on initial magnetic resonance imaging (P = 0.002) and optic neuritis (P = 0.01) were more frequent in the favourable course group.
CONCLUSION
The herein identified initial CSF protein levels, in addition to the clinical and radiological parameters at disease onset, have predictive value for long-term disability in MS cases.
Topics: Humans; Multiple Sclerosis; Prognosis; Prospective Studies; Optic Neuritis; Optic Nerve; Magnetic Resonance Imaging; Disease Progression
PubMed: 37339131
DOI: 10.1371/journal.pone.0287463 -
International Journal of Molecular... Nov 2023Intrauterine growth restriction (IUGR) remains a significant concern in modern obstetrics, linked to high neonatal health problems and even death, as well as childhood...
Intrauterine growth restriction (IUGR) remains a significant concern in modern obstetrics, linked to high neonatal health problems and even death, as well as childhood disability, affecting adult quality of life. The role of maternal and fetus adaptation during adverse pregnancy is still not completely understood. This study aimed to investigate the disturbance in biological processes associated with isolated IUGR via blood plasma proteomics. The levels of 125 maternal plasma proteins were quantified by liquid chromatography-multiple reaction monitoring mass spectrometry (LC-MRM MS) with corresponding stable isotope-labeled peptide standards (SIS). Thirteen potential markers of IUGR (Gelsolin, Alpha-2-macroglobulin, Apolipoprotein A-IV, Apolipoprotein B-100, Apolipoprotein(a), Adiponectin, Complement C5, Apolipoprotein D, Alpha-1B-glycoprotein, Serum albumin, Fibronectin, Glutathione peroxidase 3, Lipopolysaccharide-binding protein) were found to be inter-connected in a protein-protein network. These proteins are involved in plasma lipoprotein assembly, remodeling, and clearance; lipid metabolism, especially cholesterol and phospholipids; hemostasis, including platelet degranulation; and immune system regulation. Additionally, 18 proteins were specific to a particular type of IUGR (early or late). Distinct patterns in the coagulation and fibrinolysis systems were observed between isolated early- and late-onset IUGR. Our findings highlight the complex interplay of immune and coagulation factors in IUGR and the differences between early- and late-onset IUGR and other placenta-related conditions like PE. Understanding these mechanisms is crucial for developing targeted interventions and improving outcomes for pregnancies affected by IUGR.
Topics: Pregnancy; Adult; Infant, Newborn; Female; Humans; Child; Fetal Growth Retardation; Proteomics; Quality of Life; Fetus; Placenta
PubMed: 38069155
DOI: 10.3390/ijms242316832 -
Biomedicines Jun 2023Metastasis is a serious and often life-threatening condition, representing the leading cause of death among women with breast cancer (BC). Although the current clinical...
Metastasis is a serious and often life-threatening condition, representing the leading cause of death among women with breast cancer (BC). Although the current clinical classification of BC is well-established, the addition of minimally invasive laboratory tests based on peripheral blood biomarkers that reflect pathological changes in the body is of utmost importance. In the current study, the serum proteome and lipidome profiles for 50 BC patients with (25) and without (25) metastasis were studied. Targeted proteomic analysis for concertation measurements of 125 proteins in the serum was performed via liquid chromatography-multiple reaction monitoring mass spectrometry (LC-MRM MS) using the BAK 125 kit (MRM Proteomics Inc., Victoria, BC, Canada). Untargeted label-free lipidomic analysis was performed using liquid chromatography coupled to tandem mass-spectrometry (LC-MS/MS), in both positive and negative ion modes. Finally, 87 serum proteins and 295 lipids were quantified and showed a moderate correlation with tumor grade, histological and biological subtypes, and the number of lymph node metastases. Two highly accurate classifiers that enabled distinguishing between metastatic and non-metastatic BC were developed based on proteomic (accuracy 90%) and lipidomic (accuracy 80%) features. The best classifier (91% sensitivity, 89% specificity, AUC = 0.92) for BC metastasis diagnostics was based on logistic regression and the serum levels of 11 proteins: alpha-2-macroglobulin, coagulation factor XII, adiponectin, leucine-rich alpha-2-glycoprotein, alpha-2-HS-glycoprotein, Ig mu chain C region, apolipoprotein C-IV, carbonic anhydrase 1, apolipoprotein A-II, apolipoprotein C-II and alpha-1-acid glycoprotein 1.
PubMed: 37509426
DOI: 10.3390/biomedicines11071786 -
Cartilage Oct 2023α2-Macroglobulin (A2M) can prevent cartilage degeneration by blocking many types of cartilage-degrading enzymes, but the mechanism remains to be clarified. This study...
OBJECTIVES
α2-Macroglobulin (A2M) can prevent cartilage degeneration by blocking many types of cartilage-degrading enzymes, but the mechanism remains to be clarified. This study aimed to test that A2M protects against cartilage degeneration by promoting chondrocyte proliferation and cartilage matrix synthesis via inducing proliferating cell nuclear antigen (PCNA).
DESIGN
The cartilage degeneration of the anterior cruciate ligament transection (ACLT) model was evaluated by Safranin O-fast green staining, and articular cartilage degeneration was graded using the Osteoarthritis Research Society International (OARSI)-modified Mankin criteria. The chondrocyte proliferation was detected by 5-Bromodeoxyuridinc (BrdU), MTT, and Cell Counting Kit-8 (CCK8) methods. The chondrocyte apoptosis was detected by lactate dehydrogenase (LDH) assay and Annexin PI staining with the flow cytometer. The glycosaminoglycan (sGAG) and aggrecan in culture supernatant were measured by enzyme-linked immunosorbent assay (ELISA). Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to analyze the type II collagen and aggrecan mRNA expression. The PCNA protein expression was analyzed by western blot and immunofluorescent staining.
RESULTS
A2M can attenuate cartilage degeneration in ACLT rats. The OARSI scores for cartilage degeneration in the A2M group were lower than those in the phosphate-buffered saline (PBS) group. A2M can promote chondrocyte proliferation and inhibit chondrocyte apoptosis, promote the cartilage matrix synthesis in chondrocytes (type II collagen and aggrecan), and culture supernatant (sGAG and aggrecan). At the same time, it also up-regulated the PCNA protein expression in chondrocytes.
CONCLUSIONS
A2M can promote chondrocyte proliferation and cartilage matrix synthesis via inducing PCNA expression.
PubMed: 37872706
DOI: 10.1177/19476035231207776 -
Frontiers in Veterinary Science 2023The relationship between epilepsy and cognitive dysfunction has been investigated in canines, and memory impairment was prevalent in dogs with epilepsy. Additionally,...
INTRODUCTION
The relationship between epilepsy and cognitive dysfunction has been investigated in canines, and memory impairment was prevalent in dogs with epilepsy. Additionally, canines with epilepsy have greater amyloid-β (Aβ) accumulation and neuronal degeneration than healthy controls. The present study investigated plasma Aβ levels and performed proteomic profiling in dogs with refractory epilepsy and healthy dogs.
METHODS
In total, eight dogs, including four healthy dogs and four dogs with epilepsy, were included in the study. Blood samples were collected to analyze Aβ levels and perform proteomic profiling. Changes in the plasma proteomic profiles of dogs were determined by nano liquid chromatography tandem mass spectrometry.
RESULTS AND DISCUSSION
The plasma Aβ level was significantly higher in dogs with epilepsy (99 pg/mL) than in healthy dogs (5.9 pg/mL). In total, 155 proteins were identified, and of these, the expression of 40 proteins was altered in epilepsy. Among these proteins, which are linked to neurodegenerative diseases, 10 (25%) were downregulated in dogs with epilepsy, whereas 12 (30%) were upregulated. The expression of the acute phase proteins haptoglobin and α2-macroglobulin significantly differed between the groups. Complement factor H and ceruloplasmin were only detected in epilepsy dogs, suggesting that neuroinflammation plays a role in epileptic seizures. Gelsolin, which is involved in cellular processes and cytoskeletal organization, was only detected in healthy dogs. Gene Ontology annotation revealed that epilepsy can potentially interfere with biological processes, including cellular processes, localization, and responses to stimuli. Seizures compromised key molecular functions, including catalytic activity, molecular function regulation, and binding. Defense/immunity proteins were most significantly modified during the development of epilepsy. In Kyoto Encyclopedia of Genes and Genomes pathway analysis, complement and coagulation cascades were the most relevant signaling pathways affected by seizures. The findings suggested that haptoglobin, ceruloplasmin, α2-macroglobulin, complement factor H, and gelsolin play roles in canine epilepsy and Aβ levels based on proteomic profiling. These proteins could represent diagnostic biomarkers that, after clinical validation, could be used in veterinary practice as well as proteins relevant to disease response pathways. To determine the precise mechanisms underlying these relationships and their implications in canine epilepsy, additional research is required.
PubMed: 38192726
DOI: 10.3389/fvets.2023.1258244