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Nutrients Aug 2022The therapeutic effects of food rich in ellagitannins have been established to stem from its microbial metabolite, urolithin. Over the past decade, there has been a... (Review)
Review
UNLABELLED
The therapeutic effects of food rich in ellagitannins have been established to stem from its microbial metabolite, urolithin. Over the past decade, there has been a growing trend in urolithin research pertaining to its pharmacological properties. The purpose of this systematic review is to collate and synthesise all available data on urolithin's therapeutic ability, to highlight its potential as a pharmaceutical agent, and prospective direction on future research.
METHODS
This systematic review was written based on the PRISMA guideline and was conducted across Ovid via Embase, Ovid MEDLINE, Cochrane Central Register for Controlled Trials, and Web of Science Core Collection.
RESULTS
A total of 41 animal studies were included in this systematic review based on the appropriate keyword. The included studies highlighted the neuroprotective, anti-metabolic disorder activity, nephroprotective, myocardial protective, anti-inflammatory, and musculoskeletal protection of urolithin A, B, and its synthetic analogue methylated urolithin A. The Sirt1, AMPK, and PI3K/AKT/mTOR signalling pathways were reported to be involved in the initiation of autophagy and mitochondrial biogenesis by urolithin A.
CONCLUSIONS
This review methodically discusses the therapeutic prospects of urolithins and provides scientific justification for the potential development of urolithin A as a potent natural mitophagy inducer for anti-ageing purposes.
Topics: Animals; Coumarins; Hydrolyzable Tannins; Phosphatidylinositol 3-Kinases; Prospective Studies
PubMed: 36079752
DOI: 10.3390/nu14173494 -
Cancer Medicine Feb 2023Cutaneous adverse effects (AEs) are common following the phosphoinositide-3-kinase (PI3K) inhibitors treatment. We aim to estimate the incidence and risk of PI3K... (Meta-Analysis)
Meta-Analysis Review
Risk of cutaneous adverse events in cancer patients treated with phosphatidylinositol-3-kinase inhibitors: A systematic review and meta-analysis of randomized controlled trials.
BACKGROUND
Cutaneous adverse effects (AEs) are common following the phosphoinositide-3-kinase (PI3K) inhibitors treatment. We aim to estimate the incidence and risk of PI3K inhibitor-related cutaneous AEs.
METHODS
The protocol was submitted to the PROSPERO registry. We searched ClinicalTrials.gov and international databases up to July 29, 2022. Meta-analysis was conducted by using risk ratios (RRs) with 95% confidence intervals (CIs).
RESULTS
Fourteen randomized controlled trials (RCTs) comprising 3877 patients were analyzed in this study. Compared with control arms, PI3K inhibitors showed a significant increase in the risk of all-grade rash, high-grade rash, and serious rash events (RR 2.29, 95% CI 1.58-3.31, p < 0.00001; RR 9.34, 95% CI 4.21-20.69, p < 0.00001; RR 5.11, 95% CI 2.11-12.36, p = 0.0003). The overall incidences of all-grade rash and high-grade rash were 26.2% (592/2257) and 4.4% (66/1487). Subgroup analyses of all-grade rash according to cancer types and PI3K inhibitor assignations identified the significant associations. PI3K inhibitors also significantly increased the risk of pruritus and dry skin (RR 1.63, 95% CI 1.14-2.33, p = 0.007; RR 3.34, 95% CI 2.30-4.85, p < 0.00001), with incidences of 13.4% (284/2115) and 9.8% (141/1436) in the treatment group.
CONCLUSION
There is a significantly increased risk of some cutaneous AEs in patients using PI3K inhibitors. Advance intervention is recommended in case of severe and life-threatening events. Further research is required to investigate the risk factors and pathogenesis.
Topics: Humans; Randomized Controlled Trials as Topic; Neoplasms; Phosphoinositide-3 Kinase Inhibitors; Exanthema; Phosphatidylinositol 3-Kinases; Phosphatidylinositols
PubMed: 35986570
DOI: 10.1002/cam4.5153 -
Biomedicine & Pharmacotherapy =... Sep 2022Development and identification of molecular compounds capable of killing or inhibiting transformed cells promoting carcinogenesis without inducing toxic effects to the... (Review)
Review
Development and identification of molecular compounds capable of killing or inhibiting transformed cells promoting carcinogenesis without inducing toxic effects to the normal cells are of utmost significance. A systematic review was conducted in screening for important literature was extensively performed by searching the Web of Science, Ovid, BMC Springer, Elsevier, Embase, and MEDLINE databases for optimum selectivity. Google Scholar was also used to supplement information. Pharmacotherapeutic biomolecules active against colon cancer carcinogenesis in Musa acuminata and Musa balbisiana (bananas), Punica granatum L (pomegranate), Glycine max (Soybean), Brassica oleracea L var. italica Plenck (Broccoli), and Hibiscus rosa-sinesis and Hibiscus sabdariffa (hibiscus) were evaluated. Signaling pathways like phosphatidylinositol 3-kinase (PI3K), mitogen-activated protein kinase (MAPK), protein kinase B (AKT), and nuclear factor-kappa B (NFκB) correlate the mediation of COX-2 expression. Increased levels of COX-2 are correlated with the occurrence and progression of colon cancer. Natural antioxidants in herbal plants including polyphenols and carotenoids inhibit the oxidation of lipids, proteins, and nucleic acids and thereby preventing the initiation of oxidizing chain reactions. These bioactive compounds should be considered an important dietary supplement.
Topics: Carcinogenesis; Colonic Neoplasms; Cyclooxygenase 2; Hibiscus; Humans; Phosphatidylinositol 3-Kinases; Plants, Medicinal
PubMed: 35820316
DOI: 10.1016/j.biopha.2022.113383 -
European Neuropsychopharmacology : the... Aug 2022Schizophrenia (SZ), bipolar disorder (BD), and major depressive disorder (MDD) are major mental disorders that affect a significant proportion of the global population....
Schizophrenia (SZ), bipolar disorder (BD), and major depressive disorder (MDD) are major mental disorders that affect a significant proportion of the global population. Advancing our knowledge of the pathophysiology of these disorders and identifying biomarkers are urgent needs for developing objective diagnostic tests and new therapeutics. In this study, we performed a systematic review and then extracted, curated, and analyzed proteomics data from published studies, aiming to assess the proteome in peripheral blood of individuals with SZ, BD, or MDD. Then, we performed pathway and network analyses to illuminate the biological themes concatenated by the differentially expressed proteins by systematically interrogating the literature to uncover biological pathways with more robust biological meaning. We identified 486 differentially expressed proteins from 51 studies across the three disorders with 9,423 participants. The great majority of pathways were common to SZ, BD, and MDD. They were related to the immune system, including signaling by interleukins, Toll-like receptor signaling pathway, and complement cascade, and to signal transduction, notably MAPK1/MAPK3 signaling, PI3K-Akt Signaling Pathway, Focal Adhesion-PI3K-Akt-mTOR-signaling, rhodopsin-like receptors, GPCR signaling, and the JAK-STAT signaling pathway. Other shared pathways included advanced glycosylation end-product receptor signaling, Regulation of Insulin-like Growth Factor, cholesterol metabolism, and IL-17 signaling pathway. Pathways shared between SZ and BD were integrin cell-surface interactions, GRB2:SOS provides linkage to MAPK signaling for integrins, and syndecan interactions. Shared between BD and MDD were the NRF2 pathway and signaling by EGFR pathways. Our findings advance our understanding of the protein variations and associations with these disorders, which are useful for accelerating biomarker development and drug discovery.
Topics: Biomarkers; Depressive Disorder, Major; Drug Discovery; Humans; Mental Disorders; Phosphatidylinositol 3-Kinases; Proteome; Proto-Oncogene Proteins c-akt
PubMed: 35763977
DOI: 10.1016/j.euroneuro.2022.06.001 -
Theriogenology Sep 2022Modulation of phosphoinositide 3-kinase/protein kinase B/phosphatase and tensin homologue (PI3K/AKT/PTEN) pathway in mammals yields mixed results. A deep understanding...
Role of phosphoinositide 3-kinase/ protein kinase B/ phosphatase and tensin homologue (PI3K/AKT/PTEN) pathway inhibitors during in vitro maturation of mammalian oocytes on in vitro embryo production: A systematic review.
Modulation of phosphoinositide 3-kinase/protein kinase B/phosphatase and tensin homologue (PI3K/AKT/PTEN) pathway in mammals yields mixed results. A deep understanding of its regulation can be a powerful tool for better in vitro blastocyst production. This systematic review aims to map the evidence of PI3K/AKT/PTEN pathway modulation during in vitro maturation (IVM), to assess its effects on meiosis resumption and nuclear maturation progression of mammalian oocytes, and their impacts on embryo development and quality. A total of 1058 articles were screened in three databases, and 22 articles were included. Fifty-two IVM assessments were identified, among which 11 evaluated blastocyst yield. Three PI3K inhibitors (3-methyladenine, Wortmannin, and LY294002) and one AKT inhibitor (SH6) were investigated. The impact of this pathway modulation on meiosis resumption in swines and murines was not well established, depending on the inhibitor used, concentration, and media supplementation, while in bovines, resumption seems to be independent of PI3K/AKT/PTEN pathway. However, progression to metaphase II (MII) is highly controlled by this pathway on both bovines and swines. Studies that focused on the inhibition reversibility showed that the removal of the modulator produced MII rates similar to the control group. Experiments that aimed to temporarily block meiosis resumption or reduce PI3K activity resulted in blastocyst production equal to or even higher than control groups. Altogether, these data indicate the paramount potential of this pathway as a possible strategy to improve overall in vitro embryo production efficiency, by synchronizing both nuclear and cytoplasmic maturation.
Topics: Animals; In Vitro Oocyte Maturation Techniques; Mammals; Meiosis; Oocytes; Phosphatidylinositol 3-Kinase; Phosphatidylinositol 3-Kinases; Phosphoric Monoester Hydrolases; Proto-Oncogene Proteins c-akt; Tensins
PubMed: 35724451
DOI: 10.1016/j.theriogenology.2022.06.009 -
Cancer Treatment Reviews Jul 2022Despite promising results following targeted treatment with human epidermal growth factor receptor 2 (HER2)-inhibitors in HER2-positive gastric and esophageal... (Review)
Review
INTRODUCTION
Despite promising results following targeted treatment with human epidermal growth factor receptor 2 (HER2)-inhibitors in HER2-positive gastric and esophageal adenocarcinoma (GEA), prognosis remains dismal. Many patients ultimately demonstrate progression following treatment due to resistance to HER2-targeted therapy. Here, we describe the potential primary and secondary resistance mechanisms to HER2-targeted therapy in GEA.
METHODS
We systematically searched PubMed/MEDLINE, EMBASE, and CENTRAL for eligible studies describing changes that were associated with drug resistance. Study quality was assessed using an adjusted version of the OHAT risk of bias tool. Quality of proposed resistance mechanisms was assessed using predefined criteria.
RESULTS
In total, 913 records were screened, of which 73 were included that investigated mechanisms of resistance against anti-HER2 treatment in cell lines, xenograft models, patient tissue samples, and publicly available datasets. HER2-targeted therapy resistance was found to be caused by HER2 receptor changes, upregulation of compensatory receptors, (re)activation of downstream signaling pathways like PI3K/AKT and MAPK, epithelial-to-mesenchymal transition, acquirement of stem cell-like properties, alterations in cell cycle related genes, cellular metabolism, and drug pharmacokinetics.
DISCUSSION
Several different mechanisms can contribute to drug resistance to anti-HER2 treatment in GEA, mainly through loss of or mutations in the HER2 receptor and upregulation of alternative receptors such as MET, HER3, and FGFRs. Despite these preclinical results, methods to overcome the proposed resistance mechanisms in the clinical setting are lacking. Therefore, further investigation of therapy resistance in GEA patients treated with HER2 targeted therapy is essential to overcome resistance and improve treatment outcome of these patients.
Topics: Adenocarcinoma; Animals; Cell Line, Tumor; Drug Resistance, Neoplasm; Esophageal Neoplasms; Humans; Phosphatidylinositol 3-Kinases; Receptor, ErbB-2; Stomach Neoplasms
PubMed: 35689885
DOI: 10.1016/j.ctrv.2022.102418 -
Serine-Arginine Protein Kinase 1 (SRPK1): a systematic review of its multimodal role in oncogenesis.Molecular and Cellular Biochemistry Oct 2022Alternative splicing is implicated in each of the hallmarks of cancer, and is mechanised by various splicing factors. Serine-Arginine Protein Kinase 1 (SRPK1) is an... (Review)
Review
Alternative splicing is implicated in each of the hallmarks of cancer, and is mechanised by various splicing factors. Serine-Arginine Protein Kinase 1 (SRPK1) is an enzyme which moderates the activity of splicing factors rich in serine/arginine domains. Here we review SRPK1's relationship with various cancers by performing a systematic review of all relevant published data. Elevated SRPK1 expression correlates with advanced disease stage and poor survival in many epithelial derived cancers. Numerous pre-clinical studies investigating a host of different tumour types; have found increased SRPK1 expression to be associated with proliferation, invasion, migration and apoptosis in vitro as well as tumour growth, tumourigenicity and metastasis in vivo. Aberrant SRPK1 expression is implicated in various signalling pathways associated with oncogenesis, a number of which, such as the PI3K/AKT, NF-КB and TGF-Beta pathway, are implicated in multiple different cancers. SRPK1-targeting micro RNAs have been identified in a number of studies and shown to have an important role in regulating SRPK1 activity. SRPK1 expression is also closely related to the response of various tumours to platinum-based chemotherapeutic agents. Future clinical applications will likely focus on the role of SRPK1 as a biomarker of treatment resistance and the potential role of its inhibition.
Topics: Arginine; Arginine Kinase; Carcinogenesis; Cell Transformation, Neoplastic; Humans; NF-kappa B; Neoplasms; Phosphatidylinositol 3-Kinases; Protein Serine-Threonine Kinases; Proto-Oncogene Proteins c-akt; RNA Splicing Factors; Serine; Transforming Growth Factor beta
PubMed: 35583632
DOI: 10.1007/s11010-022-04456-7 -
International Journal of Molecular... Apr 2022Ovarian endometriosis may increase the risk of malignancy. Several studies have suggested atypical endometriosis as the direct precursor of endometriosis-associated... (Review)
Review
Ovarian endometriosis may increase the risk of malignancy. Several studies have suggested atypical endometriosis as the direct precursor of endometriosis-associated ovarian cancer. We performed an advanced, systematic search of the online medical databases PubMed and Medline. The search revealed = 40 studies eligible for inclusion in this systematic review. Of these, = 39 were finally included. The results from included studies are characterized by high heterogeneity, but some consistency has been found for altered expression in phosphoinositide 3-kinase (PI3K)/AKT/mTOR pathway, ARID1a, estrogen and progesterone receptors, transcriptional, nuclear, and growth factors in atypical endometriosis. Although many targets have been proposed as biomarkers for the presence of atypical endometriosis, none of them has such strong evidence to justify their systematic use in clinical practice, and they all need expensive molecular analyses. Further well-designed studies are needed to validate the evidence on available biomarkers and to investigate novel serum markers for atypical endometriosis.
Topics: Biomarkers; Carcinoma, Ovarian Epithelial; Endometriosis; Female; Humans; Ovarian Neoplasms; Phosphatidylinositol 3-Kinases; Precancerous Conditions
PubMed: 35457244
DOI: 10.3390/ijms23084425 -
Advanced Science (Weinheim,... May 2022Gaseous molecules have been increasingly explored for therapeutic development. Here, following an analytical background introduction, a systematic review of medical gas... (Review)
Review
Gaseous molecules have been increasingly explored for therapeutic development. Here, following an analytical background introduction, a systematic review of medical gas research is presented, focusing on tissue protections, mechanisms, data tangibility, and translational challenges. The pharmacological efficacies of carbon monoxide (CO) and xenon (Xe) are further examined with emphasis on intracellular messengers associated with cytoprotection and functional improvement for the CNS, heart, retina, liver, kidneys, lungs, etc. Overall, the outcome supports the hypothesis that readily deliverable "biological gas" (CO, H , H S, NO, O , O , and N O) or "noble gas" (He, Ar, and Xe) treatment may preserve cells against common pathologies by regulating oxidative, inflammatory, apoptotic, survival, and/or repair processes. Specifically, CO, in safe dosages, elicits neurorestoration via igniting sGC/cGMP/MAPK signaling and crosstalk between HO-CO, HIF-1α/VEGF, and NOS pathways. Xe rescues neurons through NMDA antagonism and PI3K/Akt/HIF-1α/ERK activation. Primary findings also reveal that the need to utilize cutting-edge molecular and genetic tactics to validate mechanistic targets and optimize outcome consistency remains urgent; the number of neurotherapeutic investigations is limited, without published results from large in vivo models. Lastly, the broad-spectrum, concurrent multimodal homeostatic actions of medical gases may represent a novel pharmaceutical approach to treating critical organ failure and neurotrauma.
Topics: Carbon Monoxide; Gases; Pharmaceutical Preparations; Phosphatidylinositol 3-Kinases; Xenon
PubMed: 35243825
DOI: 10.1002/advs.202104136 -
Journal of Cancer Research and Clinical... Jun 2022Purpose colorectal cancer (CRC) is one of the most commonly diagnosed cancers worldwide. Some evidence has shown that aspirin can reduce the morbidity and mortality of... (Meta-Analysis)
Meta-Analysis
UNLABELLED
Purpose colorectal cancer (CRC) is one of the most commonly diagnosed cancers worldwide. Some evidence has shown that aspirin can reduce the morbidity and mortality of CRC. The aim of this meta-analysis was to compare standard care of patients with CRC and standard care with the addition of aspirin in terms of the survival benefit.
METHODS
The systematic search was conducted by two independent reviewers in the databases PubMed and Web of Science. Survival data were extracted from studies published before July 2019. We searched for randomised controlled trials, cohort studies and case-control studies.
RESULTS
We included 27 studies in our meta-analysis. There was a sample size of 237,245 patients overall. Aspirin use after diagnosis was associated with an improvement in CRC-specific survival with a hazard ratio (HR) for cancer-related death of 0.74 (95% CI: 0.62-0.89). Our analysis of overall survival data revealed reduced mortality with an HR of 0.82 (95% CI: 0.74-0.90). Patients with the phosphatidylinositol-4, 5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) mutation profited from postdiagnosis aspirin use (HR = 0.74, 95% CI: 0.56-0.97). For a high expression of prostaglandin-endoperoxide synthase 2 (PTGS2) = COX-2, we found an HR of 0.65 (95% CI: 0.52-0.82).
CONCLUSION
Aspirin can improve the outcome of patients with CRC. PIK3CA mutation status and high expression of PTGS2 are associated with longer survival. However, randomised controlled trials are needed to investigate postdiagnosis aspirin use in CRC patients taking into account cancer stage and gene expression.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Case-Control Studies; Colorectal Neoplasms; Cyclooxygenase 2; Humans; Proportional Hazards Models; Randomized Controlled Trials as Topic
PubMed: 35171329
DOI: 10.1007/s00432-022-03942-1