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Journal of Pharmacy & Bioallied Sciences Aug 2020Diabetes mellitus is an endocrinal disorder affecting worldwide and the disease incidence is rising alarmingly high. The effects of diabetes on tooth development are... (Review)
Review
Diabetes mellitus is an endocrinal disorder affecting worldwide and the disease incidence is rising alarmingly high. The effects of diabetes on tooth development are explored by limited studies and their molecular insights are very rarely studied. This systematic review is aimed to provide the best scientific literature source on the molecular insights into odontogenesis in hyperglycemic environment caused by diabetes mellitus or by maternal diabetes on the offspring. The literature search was conducted on the databases, namely PubMed, PubMed Central, Cochrane, and Scopus. The original studies exploring the alterations in the molecular pathways of odontogenesis in diabetes mellitus were selected. Data were extracted, chosen, and evaluated by two independent researchers. At the end of thorough data search, four articles were eligible for the review. Three articles brought out the molecular pathways involved in the offspring of gestational diabetes through animal models. Fourth article was an study, which treated the stem cells in hyperglycemic environment and drafted the molecular pathway. The altered molecular pathways in dental epithelial stem cells (DESCs), dental papilla cells (DPCs), and stem cells from apical papilla were studied and empowered with statistical analysis. Thus with this systematic review, we conclude that apurinic/apyrimidinic endonuclease1 downregulation causing deoxyribonucleic acid hypermethylation and gene silencing, activation of toll-like receptor-4/nuclear factor kappa B (TLR4/NF-κB) pathway are involved in suppressing cell proliferation and accelerated apoptosis in DESCs in high glucose environment. DPCs are suppressed from odonto differentiation by activation of TLR4 signaling and resulting inhibition of SMAD1/5/9 phosphorylation in diabetic condition. NF-κB pathway activation causes decreased cell proliferation and enhanced differentiation in apical papilla stem cells in hyperglycemia. Further studies targeting various stages of odontogenesis can reveal more molecular insight.
PubMed: 33149430
DOI: 10.4103/jpbs.JPBS_159_20 -
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 -
Frontiers in Pharmacology 2023Alzheimer's disease (AD) is a degenerative disease of the nervous system. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), a drug used to treat type 2 diabetes,...
Alzheimer's disease (AD) is a degenerative disease of the nervous system. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), a drug used to treat type 2 diabetes, have been shown to have neuroprotective effects. This systematic review and meta-analysis evaluated the effects and potential mechanisms of GLP-1 RAs in AD animal models. 26 studies were included by searching relevant studies from seven databases according to a predefined search strategy and inclusion criteria. Methodological quality was assessed using SYRCLE's risk of bias tool, and statistical analysis was performed using ReviewManger 5.3. The results showed that, in terms of behavioral tests, GLP-1 RAs could improve the learning and memory abilities of AD rodents; in terms of pathology, GLP-1 RAs could reduce Aβ deposition and phosphorylated tau levels in the brains of AD rodents. The therapeutic potential of GLP-1 RAs in AD involves a range of mechanisms that work synergistically to enhance the alleviation of various pathological manifestations associated with the condition. A total of five clinical trials were retrieved from ClinicalTrials.gov. More large-scale and high-quality preclinical trials should be conducted to more accurately assess the therapeutic effects of GLP-1 RAs on AD.
PubMed: 37771725
DOI: 10.3389/fphar.2023.1205207 -
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 Oncology 2022ANO1, a calcium-activated chloride channel (CACC), is also known as transmembrane protein 16A (TMEM16A). It plays a vital role in the occurrence, development,...
ANO1, a calcium-activated chloride channel (CACC), is also known as transmembrane protein 16A (TMEM16A). It plays a vital role in the occurrence, development, metastasis, proliferation, and apoptosis of various malignant tumors. This article reviews the mechanism of ANO1 involved in the replication, proliferation, invasion and apoptosis of various malignant tumors. Various molecules and Stimuli control the expression of ANO1, and the regulatory mechanism of ANO1 is different in tumor cells. To explore the mechanism of ANO1 overexpression and activation of tumor cells by studying the different effects of ANO1. Current studies have shown that ANO1 expression is controlled by 11q13 gene amplification and may also exert cell-specific effects through its interconnected protein network, phosphorylation of different kinases, and signaling pathways. At the same time, ANO1 also resists tumor apoptosis and promotes tumor immune escape. ANO1 can be used as a promising biomarker for detecting certain malignant tumors. Further studies on the channels and the mechanism of protein activity of ANO1 are needed. Finally, the latest inhibitors of ANO1 are summarized, which provides the research direction for the tumor-promoting mechanism of ANO1.
PubMed: 35734591
DOI: 10.3389/fonc.2022.922838 -
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 -
BioMed Research International 2019Chemical structures derived from marine foods are highly diverse and pharmacologically promising. In particular, chitooligosaccharides (COS) present a safe...
Chemical structures derived from marine foods are highly diverse and pharmacologically promising. In particular, chitooligosaccharides (COS) present a safe pharmacokinetic profile and a great source of new bioactive polymers. This review describes the antioxidant, anti-inflammatory, and antidiabetic properties of COS from recent publications. Thus, COS constitute an effective agent against oxidative stress, cellular damage, and inflammatory pathogenesis. The mechanisms of action and targeted therapeutic pathways of COS are summarized and discussed. COS may act as antioxidants their radical scavenging activity and by decreasing oxidative stress markers. The mechanism of COS antidiabetic effect is characterized by an acceleration of pancreatic islets proliferation, an increase in insulin secretion and sensitivity, a reduction of postprandial glucose, and an improvement of glucose uptake. COS upregulate the GLUT2 and inhibit digestive enzyme and glucose transporters. Furthermore, they resulted in reduction of gluconeogenesis and promotion of glucose conversion. On the other hand, the COS decrease inflammatory mediators, suppress the activation of NF-B, increase the phosphorylation of kinase, and stimulate the proliferation of lymphocytes. Overall, this review brings evidence from experimental data about protective effect of COS.
Topics: Animals; Anti-Inflammatory Agents; Chitin; Chitosan; Free Radical Scavengers; Gluconeogenesis; Glucose; Glucose Transporter Type 2; Humans; Hypoglycemic Agents; Oligosaccharides
PubMed: 31781615
DOI: 10.1155/2019/4568039 -
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 -
International Journal of Molecular... Jul 2022Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype that is often associated with a poorer prognosis and does not respond to hormonal therapy.... (Review)
Review
Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype that is often associated with a poorer prognosis and does not respond to hormonal therapy. Increasing evidence highlights the exploitability of Annexin A1 (AnxA1), a calcium dependent protein, as a precision medicine for TNBC. To systematically summarize the role of AnxA1 and its associated mechanisms in TNBC, we performed data mining using three main databases: PubMed, Scopus, and Ovid/Medline. The papers retrieved were based on two different sets of key words such as "Annexin A1" or "Lipocortin 1" and "Breast cancer" or "TNBC". A total of 388 articles were identified, with 210 chosen for comprehensive screening and 13 papers that met inclusion criteria were included. Current evidence from cell culture studies showed that AnxA1 expression is correlated with NF-κB, which promotes migration by activating ERK phosphorylation. AnxaA1 also activates TGF-β signaling which upregulates MMP-9 and miR196a expression to enhance epithelial-mesenchymal transition and migratory capacity of TNBC cells. AnxA1 can steer the macrophage polarization toward the M2 phenotype to create a pro-tumor immune environment. Existing research suggests a potential role of AnxA1 in the metastasis and immune landscape of TNBC tumors. Preclinical and clinical experiments are warranted to investigate the feasibility and effectiveness of targeting AnxA1 in TNBC.
Topics: Annexin A1; Cell Line, Tumor; Cell Movement; Cell Proliferation; Epithelial-Mesenchymal Transition; Humans; NF-kappa B; Triple Negative Breast Neoplasms
PubMed: 35897832
DOI: 10.3390/ijms23158256 -
Brain Sciences Apr 2020The accumulation of abnormal protein aggregates represents a universal hallmark of neurodegenerative diseases (NDDs). Post-translational modifications (PTMs) regulate... (Review)
Review
The accumulation of abnormal protein aggregates represents a universal hallmark of neurodegenerative diseases (NDDs). Post-translational modifications (PTMs) regulate protein structure and function. Dysregulated PTMs may influence the propensity for protein aggregation in NDD-proteinopathies. To investigate this, we systematically reviewed the literature to evaluate effects of PTMs on aggregation propensity for major proteins linked to the pathogenesis and/or progression of NDDs. A search of PubMed, MEDLINE, EMBASE, and Web of Science Core Collection was conducted to retrieve studies that investigated an association between PTMs and protein aggregation in seven NDDs: Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), amyotrophic lateral sclerosis (ALS), spinocerebellar ataxias, transmissible spongiform encephalopathy, and multiple sclerosis. Together, 1222 studies were identified, of which 69 met eligibility criteria. We identified that the following PTMs, in isolation or combination, potentially act as modulators of proteinopathy in NDDs: isoaspartate formation in Aβ, phosphorylation of Aβ or tau in AD; acetylation, 4-hydroxy-2-neonal modification, -GlcNAcylation or phosphorylation of α-synuclein in PD; acetylation or phosphorylation of TAR DNA-binding protein-43 in ALS, and SUMOylation of superoxide dismutase-1 in ALS; and phosphorylation of huntingtin in HD. The potential pharmacological manipulation of these aggregation-modulating PTMs represents an as-yet untapped source of therapy to treat NDDs.
PubMed: 32290481
DOI: 10.3390/brainsci10040232