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JID Innovations : Skin Science From... Jul 2022As solid organ transplantation becomes more prevalent, more individuals are living as members of the immunosuppressed population with an elevated risk for cutaneous... (Review)
Review
As solid organ transplantation becomes more prevalent, more individuals are living as members of the immunosuppressed population with an elevated risk for cutaneous squamous cell carcinoma (cSCC). Although great progress has been made in understanding the pathogenesis of cSCC in general, little is known about the drivers of tumorigenesis in immunosuppressed patients and organ-transplant recipients, specifically. This systematic review sought to synthesize information regarding the genetic and epigenetic alterations as well as changes in protein and mRNA expression that place this growing population at risk for cSCC, influence treatment response, and promote tumor aggressiveness. This review will provide investigators with a framework to identify future areas of investigation and clinicians with additional insight into how to best manage these patients.
PubMed: 35620703
DOI: 10.1016/j.xjidi.2022.100126 -
Journal of Cellular Physiology Jul 2022Pemphigus vulgaris (PV) is a potentially fatal autoimmune blistering disease characterized by cell-cell detachment (or acantholysis) and blister formation. While the... (Review)
Review
Pemphigus vulgaris (PV) is a potentially fatal autoimmune blistering disease characterized by cell-cell detachment (or acantholysis) and blister formation. While the signaling mechanisms that associate with skin/mucosal blistering are being elucidated, specific treatment strategies targeting PV-specific pathomechanisms, particularly kinase signaling, have yet to be established. Hence, the aim of this review was to systematically evaluate molecules in the class of kinases that are essential for acantholysis and blister formation and are therefore candidates for targeted therapy. English articles from PubMed and Scopus databases were searched, and included in vitro, in vivo, and human studies that investigated the role of kinases in PV. We selected studies, extracted data and assessed risk of bias in duplicates and the results were reported according to the methodology outlined by the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA). The risk of bias assessment was performed on in vivo studies utilizing SYRCLE's risk of bias tool. Thirty-five studies were included that satisfied the pathogenicity criterion of kinases in PV, the vast majority being experimental models that used PV sera (n = 13) and PV-IgG (n = 22). Inhibition of kinase activity (p38MAPK, PKC, TK, c-Src, EGFR, ERK, mTOR, BTK, and CDK2) was achieved mostly by pharmacological means. Overall, we found substantial evidence that kinase inhibition reduced PV-associated phosphorylation events and keratinocyte disassociation, prevented acantholysis, and blocked blister formation. However, the scarce adherence to standardized reporting systems and the experimental protocols/models used did limit the internal and external validity of these studies. In summary, this systematic review highlighted the pathogenic intracellular events mediated by kinases in PV acantholysis and presented kinase signaling as a promising avenue for translational research. In particular, the molecules identified and discussed in this study represent potential candidates for the development of mechanism-based interventions in PV.
Topics: Acantholysis; Autoantibodies; Blister; Humans; Immunoglobulin G; Keratinocytes; Pemphigus; Phosphorylation
PubMed: 35616233
DOI: 10.1002/jcp.30784 -
Frontiers in Pharmacology 2022Cancers are a potential cause of death worldwide and represent a massive burden for healthcare systems. Treating cancers requires substantial resources, including...
Cancers are a potential cause of death worldwide and represent a massive burden for healthcare systems. Treating cancers requires substantial resources, including skilled personnel, medications, instruments, and funds. Thus, developing cancer prevention and treatment measures is necessary for healthcare personnel and patients alike. (Polygonaceae family) is a plant used as a culinary ingredient. It exhibits several pharmacological activities, such as antibacterial, antifungal, antioxidant, anti-inflammatory, and anticancer. Several classes of phytochemical constituents of have been reported. The important ones might be polyphenol and flavonoid derivatives. In this systematic review, the activities of against cancerous cells were determined and summarized. Data were obtained through a systematic search of electronic databases (EMBASE, PubMed, Scopus, Thai Thesis Database, Science Direct and Clinical Key). Eight studies met the eligibility criteria. The cancerous cell lines used in the studies were lymphoma, leukemia, oral, lung, breast, colon, and liver cancer cells. Based on this review, extracts significantly affected Epstein-Barr virus (EBV) genome-carrying human lymphoblastoid (Raji), mouse lymphocytic leukemia (P388), human acute lymphocytic leukemia (Jurkat), breast adenocarcinoma (MCF-7), human colon adenocarcinoma (HT-29), human T lymphoblast (MOLT-4), human promyelocytic leukemia cell line (HL-60), human hepatocellular carcinoma (HepG2), and oral squamous cell carcinoma (SAS, SCC-9, HSC-3) through induction of cell apoptosis, arrest of the cell cycle, inhibition of cell proliferation, migration, and colonization. The molecular mechanism of against cancers was reported to involve suppressing essential proteins required for cell proliferation, colonization, migration, apoptosis, and angiogenesis. They were survivin, cyclin-D, cyclooxygenase 2 (COX-2), matrix metalloproteinase-9 (MMP-9), and vascular endothelial growth factor A (VEGF-A). The extract of was also involved in the protein kinase B (Akt)/mammalian target of rapamycin (mTOR) pathway by inhibiting the expression of Akt, phosphorylated Akt, mTOR, and phosphorylated mTOR. From the key results of this review, is a promising chemotherapy and chemopreventive agent. Further investigation of its pharmacological activity and mechanism of action should be conducted using standardized extracts. experiments and clinical trials are required to confirm the anticancer activity.
PubMed: 35571080
DOI: 10.3389/fphar.2022.875016 -
Frontiers in Aging Neuroscience 2022Because of high prevalence of Alzheimer's disease (AD) in low- and middle-income countries (LMICs), there is an urgent need for inexpensive and minimally invasive...
BACKGROUND
Because of high prevalence of Alzheimer's disease (AD) in low- and middle-income countries (LMICs), there is an urgent need for inexpensive and minimally invasive diagnostic tests to detect biomarkers in the earliest and asymptomatic stages of the disease. Blood-based biomarkers are predicted to have the most impact for use as a screening tool and predict the onset of AD, especially in LMICs. Furthermore, it has been suggested that panels of markers may perform better than single protein candidates.
METHODS
Medline/Pubmed was searched to identify current relevant studies published from January 2016 to December 2020. We included all full-text articles examining blood-based biomarkers as a set of protein markers or panels to aid in AD's early diagnosis, prognosis, and characterization.
RESULTS
Seventy-six articles met the inclusion criteria for systematic review. Majority of the studies reported plasma and serum as the main source for biomarker determination in blood. Protein-based biomarker panels were reported to aid in AD diagnosis and prognosis with better accuracy than individual biomarkers. Conventional (amyloid-beta and tau) and neuroinflammatory biomarkers, such as amyloid beta-42, amyloid beta-40, total tau, phosphorylated tau-181, and other tau isoforms, were the most represented. We found the combination of amyloid beta-42/amyloid beta-40 ratio and APOEε4 status to be most represented with high accuracy for predicting amyloid beta-positron emission tomography status.
CONCLUSION
Assessment of Alzheimer's disease biomarkers in blood as a non-invasive and cost-effective alternative will potentially contribute to early diagnosis and improvement of therapeutic interventions. Given the heterogeneous nature of AD, combination of markers seems to perform better in the diagnosis and prognosis of the disease than individual biomarkers.
PubMed: 35360215
DOI: 10.3389/fnagi.2022.683689 -
Acta Neurochirurgica Jul 2022Idiopathic normal pressure hydrocephalus (iNPH) is a neurodegenerative disease and dementia subtype involving disturbed cerebrospinal fluid (CSF) homeostasis. Patients... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Idiopathic normal pressure hydrocephalus (iNPH) is a neurodegenerative disease and dementia subtype involving disturbed cerebrospinal fluid (CSF) homeostasis. Patients with iNPH may improve clinically following CSF diversion through shunt surgery, but it remains a challenge to predict which patients respond to shunting. It has been proposed that CSF and blood biomarkers may be used to predict shunt response in iNPH.
OBJECTIVE
To conduct a systematic review and meta-analysis to identify which CSF and venous biomarkers predict shunt-responsive iNPH most accurately.
METHODS
Original studies that investigate the use of CSF and venous biomarkers to predict shunt response were searched using the following databases: Embase, MEDLINE, Scopus, PubMed, Google Scholar, and JSTOR. Included studies were assessed using the ROBINS-I tool, and eligible studies were evaluated utilising univariate meta-analyses.
RESULTS
The study included 13 studies; seven addressed lumbar CSF levels of amyloid-β 1-42, nine studies CSF levels of Total-Tau, six studies CSF levels of Phosphorylated-Tau, and seven studies miscellaneous biomarkers, proteomics, and genotyping. A meta-analysis of six eligible studies conducted for amyloid-β 1-42, Total-Tau, and Phosphorylated-Tau demonstrated significantly increased lumbar CSF Phosphorylated-Tau (- 0.55 SMD, p = 0.04) and Total-Tau (- 0.50 SMD, p = 0.02) in shunt-non-responsive iNPH, though no differences were seen between shunt responders and non-responders for amyloid-β 1-42 (- 0.26 SMD, p = 0.55) or the other included biomarkers.
CONCLUSION
This meta-analysis found that lumbar CSF levels of Phosphorylated-Tau and Total-Tau are significantly increased in shunt non-responsive iNPH compared to shunt-responsive iNPH. The other biomarkers, including amyloid-β 1-42, did not significantly differentiate shunt-responsive from shunt-non-responsive iNPH. More studies on the Tau proteins examining sensitivity and specificity at different cut-off levels are needed for a robust analysis of the diagnostic efficiency of the Tau proteins.
Topics: Amyloid beta-Peptides; Biomarkers; Humans; Hydrocephalus, Normal Pressure; Neurodegenerative Diseases; tau Proteins
PubMed: 35230552
DOI: 10.1007/s00701-022-05154-5 -
Ageing Research Reviews Apr 2022Cerebral hypoxia-ischemia (CHI) causes brain aging, neurological disorders, cognitive decline, motor function impairment, and mortality. Inhibiting death-associated... (Meta-Analysis)
Meta-Analysis Review
Neurodegenerative effect of DAPK1 after cerebral hypoxia-ischemia is associated with its post-transcriptional and signal transduction regulations: A systematic review and meta-analysis.
Cerebral hypoxia-ischemia (CHI) causes brain aging, neurological disorders, cognitive decline, motor function impairment, and mortality. Inhibiting death-associated protein kinase 1 (DAPK1) has shown therapeutic potential against CHI, but several reports contradict its protective function, mechanism of activation, and signal transduction. Here, we systematically reviewed the role and the activation mechanism of DAPK1, and quantitatively assess the efficacy of DAPK1 inhibition (DI) methods in neuroprotection, following a CHI in animal models. Embase and PubMed were searched for relevant studies. Overall, 13 studies met the inclusion criteria, and the SYRCLE Risk of bias tool (RoB) tool was used to assess RoB. StataSE 16 was used for meta-analysis and network meta-analysis (NMA). Standardized mean differences (SMD) with 95% confidence intervals (CI) were calculated to estimate the effect size. DI was associated with the reduction of brain infarct volume (BIV) [SMD = -1.70, 95% CI (-2.10, -1.30); p = 0.00], neurological score (N.S.), neuronal degeneration, with no change in the level of in cell death [SMD = -0.83, 95% CI (-2.00, 0.35); p = 0.17], indicating the protective role of DI against CHI. No differences were found in DAPK1 mRNA and protein levels [SMD = 0.50, 95% CI (-0.05, 1.04); p = 0.07] {single-study driven; upregulated after exclusion (p = 0.01, I = 36.43)}, whereas phospho-DAPK1 [SMD = -2.22, 95% CI (-3.69, -0.75); p = 0.00] was downregulated and phosphorylated myosin light chain [SMD = 3.37, 95% CI (2.51, 4.96); p = 0.00] was upregulated between CHI and sham groups. Furthermore, we performed NMA to understand the molecular level at which DI offers maximum protection against BIV. Post-transcriptional inhibition (PTI; SUCRA, 82.6%) and gene knockout showed best (KO; SUCRA, 81.3%), signal transduction inhibition (STI; SUCRA, 49.5%) offered 3 best, while catalytic activity inhibition (CAI; SUCRA, 0.3%) exhibited the lowest reduction in BIV against CHI. The results demonstrate that DI has a neuroprotective effect against CHI and DAPK1 might be regulated at the post-transcriptional and post-translational levels after CHI. Inhibiting DAPK1 at the post-transcriptional level and blocking multiple signal transduction pathways of DAPK1 could lead to better functional recovery against CHI. AVAILABILITY OF DATA AND MATERIALS: The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.
Topics: Animals; Cell Death; Death-Associated Protein Kinases; Humans; Hypoxia-Ischemia, Brain; Network Meta-Analysis; Neurodegenerative Diseases; RNA Processing, Post-Transcriptional; Signal Transduction
PubMed: 35202858
DOI: 10.1016/j.arr.2022.101593 -
Journal of Ovarian Research Nov 2021STAT3 and p-STAT3 are often overexpressed in various human tumours and participate in cancer development and progression. However, whether STAT3/p-STAT3 expression is... (Meta-Analysis)
Meta-Analysis
PURPOSE
STAT3 and p-STAT3 are often overexpressed in various human tumours and participate in cancer development and progression. However, whether STAT3/p-STAT3 expression is associated with clinicopathologic characteristics and has prognostic significance for people suffering from ovarian cancer remains controversial. We conducted a systematic review and meta-analyses to clarify the associations between STAT3/p-STAT3 expression and clinicopathologic characteristics and prognostic factors of ovarian cancer.
METHODS
A systematic electronic search in the PubMed, Embase, CNKI, and Wanfang databases was conducted to identify relevant articles published before 3 April 2021. All statistical analyses were performed using Stata 15.1.
RESULTS
We included 16 eligible studies incorporating 1747 ovarian cancer patients. The expression of STAT3/p-STAT3 was upregulated in ovarian cancer samples versus normal ovarian tissue, benign tumours and borderline tumours (OR = 10.14, p < 0.00001; OR = 9.08, P < 0.00001; OR = 4.01, p < 0.00001, respectively). STAT3/p-STAT3 overexpression was significantly correlated with FIGO stage (I-II vs. III-IV) (OR = 0.36, p < 0.00001), tumour grade (G1 + G2 vs. G3) (OR = 0.55; p = 0.001) and lymph node metastasis (yes vs. no) (OR = 3.39; p < 0.00001). High STAT3/p-STAT3 expression was correlated with poorer prognosis of ovarian cancer patients for both overall survival (OS) (HR = 1.67, p < 0.00001) and progression-free survival (PFS) (HR = 1.40, p = 0.007).
CONCLUSION
The present meta-analysis indicated that high STAT3/p-STAT3 expression is likely predictive of an unfavourable prognosis in ovarian cancer patients. Nonetheless, prospective trials are required to confirm these associations.
Topics: Biomarkers, Tumor; Female; Humans; Lymphatic Metastasis; Neoplasm Grading; Neoplasm Staging; Ovarian Neoplasms; Phosphorylation; Prognosis; Progression-Free Survival; STAT3 Transcription Factor; Survival Rate
PubMed: 34789292
DOI: 10.1186/s13048-021-00918-6 -
Redox Biology Oct 2021Postprandial oxidative stress markers in blood are generated transiently from various tissues and cells following high-fat and/or high-carbohydrate (HFHC) meals, and may... (Review)
Review
BACKGROUND
Postprandial oxidative stress markers in blood are generated transiently from various tissues and cells following high-fat and/or high-carbohydrate (HFHC) meals, and may be suppressed by certain phytonutrients, such as polyphenols and carotenoids. However, the transient presence of phytonutrients in circulation suggests that timing of consumption, relative to the meal, could be important. This systematic review investigates the effect of timing of phytonutrient intake on blood markers of postprandial oxidative processes.
METHOD
EMBASE, Medline, Scopus and Web of Science were searched up to December 2020. Eligible studies met the criteria: 1) healthy human adults; 2) phytonutrient(s) consumed in solid form within 24 h of a HFHC meal; 3) postprandial measurements of oxidative stress or antioxidants in blood; and 4) controlled study design. Cohen's d effect sizes were calculated to compare studies.
RESULTS
Nine studies, involving 256 participants, were included. Phytonutrients were consumed either at the same time, 1 h before, or the day (>12 h) before a HFHC meal. Significant decreases in blood markers - plasma lipid hydroperoxides, plasma malondialdehyde, serum sNox2-dp, serum 8-iso-PGF2α, platelet p47 phosphorylation, and Keap-1 and p47 protein levels in mononuclear cells (MNCs) - were observed where the phytonutrient was consumed together with the challenge meal (n = 4). Lack of any effect on oxidative stress markers was observed where phytonutrients were consumed with (n = 1), 1 h before (n = 1), and the day before (n = 2) the HFHC meal.
CONCLUSION
Phytonutrients consumed with a HFHC meal significantly suppressed some markers of oxidative stress in blood. Although there were only a limited number of studies, it appears that suppression appeared effective at the time of peak phytonutrient concentration in plasma. However, further studies are required to confirm the observations and systematically optimise the effect of timing.
Topics: Antioxidants; Cross-Over Studies; Humans; Malondialdehyde; Oxidative Stress; Phytochemicals; Postprandial Period
PubMed: 34488026
DOI: 10.1016/j.redox.2021.102123 -
Neurology. Clinical Practice Aug 2021There is an unmet need for reliable biomarkers to predict disease severity, prognosis, and treatment effect in patients with spinal muscular atrophy (SMA). The purpose... (Review)
Review
BACKGROUND
There is an unmet need for reliable biomarkers to predict disease severity, prognosis, and treatment effect in patients with spinal muscular atrophy (SMA). The purpose of this review is to evaluate the clinical utility of blood-based biomarkers in patients with SMA.
METHODS
A systematic review of MEDLINE, DARE, PEDro, PsycINFO, Cochrane Database, LILACS, OTSeeker, SpeechBITE, CINAHL, Scopus, Science Direct, clinicaltrial.gov, OpenGrey, and Google Scholar was performed with the last search data of June 30, 2019.
RESULTS
Survival motor neuron (SMN)-related biomarkers showed an important interpatient and cell variability with a wide overlap between SMA phenotypes and healthy controls. Several plasma protein analytes correlated with motor scores; however, validation studies are needed to rule out false positives. DNA methylation analysis distinguished between patients with mild/moderate SMA and healthy controls. Plasma phosphorylated neurofilament heavy chain (pNF-H) levels increased with disease severity and declined considerably after nusinersen treatment.
CONCLUSION
There is no sufficient evidence to support the clinical utility of SMN-related biomarkers to predict disease severity in SMA. pNF-H appears to be a promising biomarker of disease activity and treatment effect in SMA. Further studies should include longitudinal assessments of patients with SMA across functional groups and comparisons with age-matched healthy controls to evaluate the stability of putative biomarkers over time and in response to SMA therapeutics. PROSPERO registration: CRD42019139050.
PubMed: 34484951
DOI: 10.1212/CPJ.0000000000000872 -
Frontiers in Immunology 2021Primary immune regulatory disorders (PIRD) are associated with autoimmunity, autoinflammation and/or dysregulation of lymphocyte homeostasis. Autoimmune... (Meta-Analysis)
Meta-Analysis
Primary immune regulatory disorders (PIRD) are associated with autoimmunity, autoinflammation and/or dysregulation of lymphocyte homeostasis. Autoimmune lymphoproliferative syndrome (ALPS) is a PIRD due to an apoptotic defect in Fas-FasL pathway and characterized by benign and chronic lymphoproliferation, autoimmunity and increased risk of lymphoma. Clinical manifestations and typical laboratory biomarkers of ALPS have also been found in patients with a gene defect out of the Fas-FasL pathway (ALPS-like disorders). Following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA), we identified more than 600 patients suffering from 24 distinct genetic defects described in the literature with an autoimmune lymphoproliferative phenotype (ALPS-like syndromes) corresponding to phenocopies of primary immunodeficiency (PID) (), susceptibility to EBV (), antibody deficiency ( gain of function (GOF) loss of function (LOF) GOF), regulatory T-cells defects ( GOF), combined immunodeficiencies (), defects in intrinsic and innate immunity and predisposition to infection ( GOF, ) and autoimmunity/autoinflammation (). CTLA4 and LRBA patients correspond around to 50% of total ALPS-like cases. However, only 100% of CTLA4, PRKCD, TET2 and NRAS/KRAS reported patients had an ALPS-like presentation, while the autoimmunity and lymphoproliferation combination resulted rare in other genetic defects. Recurrent infections, skin lesions, enteropathy and malignancy are the most common clinical manifestations. Some approaches available for the immunological study and identification of ALPS-like patients through flow cytometry and ALPS biomarkers are provided in this work. Protein expression assays for NKG2D, XIAP, SAP, CTLA4 and LRBA deficiencies and functional studies of AKT, STAT1 and STAT3 phosphorylation, are showed as useful tests. Patients suspected to suffer from one of these disorders require rapid and correct diagnosis allowing initiation of tailored specific therapeutic strategies and monitoring thereby improving the prognosis and their quality of life.
Topics: Autoimmune Lymphoproliferative Syndrome; Early Diagnosis; Humans; Primary Immunodeficiency Diseases
PubMed: 34447369
DOI: 10.3389/fimmu.2021.671755