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Pharmacology, Biochemistry, and Behavior Feb 2023Approximately two-thirds of patients with major depressive disorder (MDD) fail to respond to conventional antidepressants, suggesting that additional mechanisms are... (Review)
Review
Approximately two-thirds of patients with major depressive disorder (MDD) fail to respond to conventional antidepressants, suggesting that additional mechanisms are involved in the MDD pathophysiology. In this scenario, the glutamatergic system represents a promising therapeutic target for treatment-resistant depression. To our knowledge, this is the first study using semantic approach with systems biology to identify potential targets involved in the fast-acting antidepressant effects of ketamine and its enantiomers as well as identifying specific targets of (R)-ketamine. We performed a systematic review, followed by a semantic analysis and functional gene enrichment to identify the main biological processes involved in the therapeutic effects of these agents. Protein-protein interaction networks were constructed, and the genes exclusively regulated by (R)-ketamine were explored. We found that the regulation of α-Amino-3-Hydroxy-5-Methyl-4-Isoxazolepropionic Acid (AMPA) receptor and N-methyl-d-aspartate (NMDA) receptor subunits-Postsynaptic Protein 95 (PSD-95), Brain Derived Neurotrophic Factor (BDNF), and Tyrosine Receptor Kinase B (TrkB) are shared by the three-antidepressant agents, reinforcing the central role of the glutamatergic system and neurogenesis on its therapeutic effects. Differential regulation of Transforming Growth Factor Beta 1 (TGF-β1) receptors-Mitogen-Activated Protein Kinases (MAPK's), Receptor Activator of Nuclear Factor-Kappa Beta Ligand (RANKL), and Serotonin Transporter (SERT) seems to be particularly involved in (R)-ketamine antidepressant effects. Our data helps further studies investigating the relationship between these targets and the mechanisms of (R)-ketamine and searching for other therapeutic compounds that share the regulation of these specific biomolecules. Ultimately, this study could contribute to improve the fast management of depressive-like symptoms with less detrimental side effects than ketamine and (S)-ketamine.
Topics: Humans; Ketamine; Depression; Depressive Disorder, Major; Systems Biology; Antidepressive Agents; Receptors, AMPA; Receptors, N-Methyl-D-Aspartate
PubMed: 36731751
DOI: 10.1016/j.pbb.2023.173523 -
Journal of Strength and Conditioning... Mar 2023Lee, CJ and Nicoll, JX. Time course evaluation of mitogen-activated protein kinase phosphorylation to resistance exercise: a systematic review. J Strength Cond Res...
Lee, CJ and Nicoll, JX. Time course evaluation of mitogen-activated protein kinase phosphorylation to resistance exercise: a systematic review. J Strength Cond Res 37(3): 710-725, 2023-Resistance exercise (RE) can increase the signaling activities of mitogen-activated protein kinases (MAPKs), specifically extracellular signal-regulated kinases 1/2 (ERK1/2), p90 ribosomal S6 kinases (p90RSK), c-Jun NH2-terminal kinases (JNK), and p38-MAPK. These RE-induced responses contribute to various intracellular processes modulating growth and development in skeletal muscles, playing an essential role in resistance training adaptations. The time course of MAPK phosphorylation to different RE conditions, such as training experience and varying loads, remains ambiguous. A systematic review was conducted to determine the effects of different post-RE recovery time points on the MAPK signaling cascade. In addition, the effects of loading and training statuses on MAPK responses were also investigated. The review was performed according to the preferred reporting items for systematic reviews and meta-analyses guidelines with a literature search incorporating 3 electronic databases. A modified version of the Downs and Black checklist was used to evaluate the methodological quality of the studies. The signaling responses were measured within a time range between immediately post-RE and >6 hours post-RE. Forty-four studies met the inclusion criteria, and all were classified as good-to-moderate methodological quality. Mitogen-activated protein kinase phosphorylation increased to different levels after RE, with the highest near the cessation of exercise. Although overall signaling was attenuated among trained individuals likely because of training adaptations, greater MAPK responses can be attributed to moderate loads of 65-85% 1RM regardless of the training experience. However, specific training-induced responses remain equivocal, and further investigations are required to determine the ideal training parameters to optimize anabolic intramuscular signaling, which may likely optimize resistance training adaptations.
Topics: Humans; Mitogen-Activated Protein Kinases; Phosphorylation; Resistance Training; Mitogen-Activated Protein Kinase 1; MAP Kinase Signaling System
PubMed: 36727997
DOI: 10.1519/JSC.0000000000004409 -
Brain and Behavior Feb 2023Neuropathic pain (NP) caused by the injury or dysfunction of the nervous system is a chronic pain state accompanied by hyperalgesia, and the available clinical treatment... (Review)
Review
BACKGROUND
Neuropathic pain (NP) caused by the injury or dysfunction of the nervous system is a chronic pain state accompanied by hyperalgesia, and the available clinical treatment is relatively scarce. Hyperalgesia mediated by pro-inflammatory factors and chemokines plays an important role in the occurrence and maintenance of NP.
DATA TREATMENT
Therefore, we conducted a systematic literature review of experimental NP (PubMed Medline), in order to find the mechanism of inducing central sensitization and explore the intervention methods of hyperalgesia caused by real or simulated injury.
RESULT
In this review, we sorted out the activation pathways of microglia, astrocytes and neurons, and the process of crosstalk among them. It was found that in NP, the microglia P2X4 receptor is the key target, which can activate the mitogen-activated protein kinase pathway inward and then activate astrocytes and outwardly activate neuronal tropomyosin receptor kinase B receptor to activate neurons. At the same time, activated neurons continue to maintain the activation of astrocytes and microglia through chemokines on CXCL13/CXCR5 and CX3CL1/CX3CR1. This crosstalk process is the key to maintaining NP.
CONCLUSION
We summarize the further research on crosstalk among neurons, microglia, and astrocytes in the central nervous system, elaborate the ways and connections of relevant crosstalk, and find potential crosstalk targets, which provides a reference for drug development and preclinical research.
Topics: Humans; Hyperalgesia; Neuroglia; Neuralgia; Neurons; Spinal Cord; Microglia; Astrocytes
PubMed: 36602945
DOI: 10.1002/brb3.2868 -
Dental Materials : Official Publication... Jan 2023Since peri-implantitis differs clinically and histopathologically from periodontitis, implant wear debris is considered to play a role in the destructive processes. This...
OBJECTIVE
Since peri-implantitis differs clinically and histopathologically from periodontitis, implant wear debris is considered to play a role in the destructive processes. This work aims to systematically review if titanium particles affect oral-related cells through changes in molecular signatures (e.g., transcriptome, proteome, epigenome), thereby promoting peri-implantitis.
METHODS
Leveraging three literature databases (Medline, Embase, Cochrane) a systematic search based on a priori defined PICOs was conducted: '-omics' studies examining titanium exposure in oral-related cells. After risk of bias assessments, lists of differentially expressed genes, proteins, and results of functional enrichment analyses were compiled. The significance of overlapping genes across multiple studies was assessed via Monte Carlo simulation and their ranking was verified using rank aggregation.
RESULTS
Out of 2104 screened articles we found 12 eligible publications. A significant overlap of gene expression in oral-related cells exposed to titanium particles was found in four studies. Furthermore, changes in biological processes like immune/inflammatory or stress response as well as toll-like receptor (TLR) and mitogen-activated protein kinase (MAPK) signaling pathways were linked to titanium in transcriptome and proteome studies. Epigenetic changes caused by titanium were detected but inconsistent.
CONCLUSION
An influence of titanium implant wear debris on the development and progression of peri-implantitis is plausible but needs to be proven in further studies. Limitations arise from small sample sizes of included studies and insufficient publication of re-analyzable data.
Topics: Humans; Peri-Implantitis; Dental Implants; Titanium; Proteome; Dental Materials
PubMed: 36526446
DOI: 10.1016/j.dental.2022.11.022 -
Pharmacological Research Jan 2023Cucurbitacin B (CuB, CHO), the most abundant and active member of cucurbitacins, which are highly oxidized tetracyclic triterpenoids. Cucurbitacins are widely... (Review)
Review
Cucurbitacin B (CuB, CHO), the most abundant and active member of cucurbitacins, which are highly oxidized tetracyclic triterpenoids. Cucurbitacins are widely distributed in a variety of plants and mainly isolated from plants in the Cucurbitaceae family. CuB is mostly obtained from the pedicel of Cucumis melo L. Modern pharmacological studies have confirmed that CuB has a broad range of pharmacological activities, with significant therapeutic effects on a variety of diseases including inflammatory diseases, neurodegenerative diseases, diabetes mellitus, and cancers. In this study the PubMed, Web of Science, Science Direct, and China National Knowledge Infrastructure (CNKI) databases were searched from 1986 to 2022. After inclusion and exclusion criteria were applied, 98 out of 2484 articles were selected for a systematic review to comprehensively summarize the pharmacological activity, toxicity, and pharmacokinetic properties of CuB. The results showed that CuB exhibits potent anti-inflammatory, antioxidant, antiviral, hypoglycemic, hepatoprotective, neuroprotective, and anti-cancer activities mainly via regulating various signaling pathways, such as the Janus kinase/signal transducer and activator of transcription-3 (JAK/STAT3), nuclear factor erythroid 2-related factor-2/antioxidant responsive element (Nrf2/ARE), nuclear factor (NF)-κB, AMP-activated protein kinase (AMPK), mitogen-activated protein kinase (MAPK), phosphoinositide 3-kinase (PI3K)/Akt, cancerous inhibitor of protein phosphatase-2A/protein phosphatase-2A (CIP2A/PP2A), Wnt, focal adhesion kinase (FAK), Notch, and Hippo-Yes-associated protein (YAP) pathways. Studies of its toxicity and pharmacokinetic properties showed that CuB has non-specific toxicity and low bioavailability. In addition, derivatives and clinical applications of CuB are discussed in this paper.
Topics: Cucurbitacins; Protein Phosphatase 2; Antioxidants; Phosphatidylinositol 3-Kinases; Triterpenes; NF-kappa B
PubMed: 36460279
DOI: 10.1016/j.phrs.2022.106587 -
The International Journal of... Dec 2022Cardiac magnetic resonance (CMR) derived left ventricular global longitudinal strain (LV-GLS) for evaluating dilated cardiomyopathy patients has been addressed in... (Meta-Analysis)
Meta-Analysis
Prognostic value of cardiac magnetic resonance derived global longitudinal strain analysis in patients with ischaemic and non-ischaemic dilated cardiomyopathy: a systematic review and meta-analysis.
Cardiac magnetic resonance (CMR) derived left ventricular global longitudinal strain (LV-GLS) for evaluating dilated cardiomyopathy patients has been addressed in studies with contradictory results. We therefore performed the first systematic review evaluating evidence on the prognostic value of CMR derived LV-GLS for ischaemic (IDCM) and non-ischaemic dilated cardiomyopathy (NDCM) patients. Systematic review (PROSPERO CRD42020171582) identified studies up to January 2021 that measured LV-GLS for predicting major adverse cardiac events among dilated cardiomyopathy patients. Studies were identified from MEDLINE, Embase and PubMed by two independent reviewers. 2099 studies were screened. Three prospective and three retrospective observational studies comprising of 1758 patients (29% IDCM patients; 71% NDCM patients) with a weighted mean follow up of 3 years (SD = 1 year) were identified. All six studies included mortality in the primary composite outcome. LV-GLS was associated with increase primary composite outcome among mild to moderately impaired left ventricular ejection fraction (LVEF) IDCM and NDCM patients (> 30%) in univariable and multivariable analysis. Association was lost among severely impaired LVEF patients (< 30%). From sensitivity analysis, LV-GLS showed significant association with death among NDCM patients (HR 1.27; 95% CI 1.10-1.46; p = 0.001; I = 59%) but insignificant for heart transplant outcome (HR 1.23; 95% CI 0.46-3.33; p = 0.68, I = 44%). LV-GLS threshold for effectively stratifying patients is - 12.5% to - 13.5%. LVEF in IDCM and NDCM became an insignificant prognostic marker in multivariable analysis. CMR LV-GLS shows promise as an independent predictor of mortality in IDCM and NDCM patients. However, in patients with LVEF < 30% LV-GLS may have less prognostic value.Prospero Registration: CRD42020171582.
Topics: Humans; Prognosis; Stroke Volume; Cardiomyopathy, Dilated; Retrospective Studies; Prospective Studies; Ventricular Function, Left; Predictive Value of Tests; Magnetic Resonance Spectroscopy
PubMed: 36445666
DOI: 10.1007/s10554-022-02679-9 -
Bioorganic Chemistry Jan 2023Discoidin domain receptors (DDRs) are one of the less explored targets for the treatment of cancer which belong to receptor tyrosine kinases family. Discoidin domain... (Review)
Review
Discoidin domain receptor inhibitors as anticancer agents: A systematic review on recent development of DDRs inhibitors, their resistance and structure activity relationship.
Discoidin domain receptors (DDRs) are one of the less explored targets for the treatment of cancer which belong to receptor tyrosine kinases family. Discoidin domain receptors (DDRs) are a collagen-activated receptor tyrosine kinase and essential for controlling cellular functions like proliferation, morphogenesis, adhesion, differentiation, invasion, matrix remodeling, and migration. Although there are many targets and their inhibitors are reported which treat cancer. But most of drugs were amalgamated with moderate to severe side effects. This results in untreated cancerous cells. One of the reasons that cancer is considered challenging to treat because the targets were mutating rapidly and the inhibitor become less potent. The target identification is a tedious task for the researchers from the early 1990 s till date. When it comes to cancer, there has not been any magical stick to treat it undisputedly. Therefore, need for discovery of new receptor may helpful to overcome these difficulties. The development of DDR inhibitors has received a lot of attention ever since the target was discovered. In this review we have reported the development of most promising DDR1 and DDR2 small molecule inhibitors from the perspective of medicinal chemistry. We have also discussed about the clinical trials, recent patents, selectivity biological activity, and structure-activity relationship (SAR) of DDR1 and DDR2 inhibitors.
Topics: Humans; Antineoplastic Agents; Discoidin Domain Receptors; Neoplasms; Receptor Protein-Tyrosine Kinases; Receptors, Mitogen; Structure-Activity Relationship
PubMed: 36384067
DOI: 10.1016/j.bioorg.2022.106215 -
Current Oncology (Toronto, Ont.) Oct 2022Breast cancer represents the most common type of cancer and is the leading cause of death due to cancer among women. Thus, the prevention and early diagnosis of breast... (Review)
Review
Breast cancer represents the most common type of cancer and is the leading cause of death due to cancer among women. Thus, the prevention and early diagnosis of breast cancer is of primary urgency, as well as the development of new treatments able to improve its prognosis. Nerve Growth Factor (NGF) is a neurotrophic factor involved in the regulation of neuronal functions through the binding of the Tropomyosin receptor kinase A (TrkA) and the Nerve Growth Factor receptor or Pan-Neurotrophin Receptor 75 (NGFR/p75NTR). In addition, its precursor (pro-NGF) can extert biological activity by forming a trimeric complex with NGFR/p75NTR and sortilin, or by binding to TrkA receptors with low affinity. Several examples of in vitro and in vivo evidence show that NGF is both synthesized and released by breast cancer cells, and has mitogen, antiapoptotic and angiogenic effects on these cells through the activation of different signaling cascades that involve TrkA and NGFR/p75NTR receptors. Conversely, pro-NGF signaling has been related to breast cancer invasion and metastasis. Other studies suggested that NGF and its receptors could represent a good diagnostic and prognostic tool, as well as promising therapeutic targets for breast cancer. In this paper, we comprehensively summarize and systematically review the current experimental evidence on this topic. INPLASY ID: INPLASY2022100017.
Topics: Female; Humans; Nerve Growth Factor; Receptor, trkA; Breast Neoplasms; Receptor, Nerve Growth Factor; Signal Transduction
PubMed: 36354700
DOI: 10.3390/curroncol29110640 -
Clinical & Translational Oncology :... Mar 2023Obesity may create a mitogenic microenvironment that influences tumor initiation and progression. The obesity-associated adipokine, leptin regulates energy metabolism... (Review)
Review
Obesity may create a mitogenic microenvironment that influences tumor initiation and progression. The obesity-associated adipokine, leptin regulates energy metabolism and has been implicated in cancer development. It has been shown that some cell types other than adipocytes can express leptin and leptin receptors in tumor microenvironments. It has been shown that peroxisome proliferator-activated receptors (PPAR) agonists can affect leptin levels and vice versa leptin can affect PPARs. Activation of PPARs affects the expression of several genes involved in aspects of lipid metabolism. In addition, PPARs regulate cancer cell progression through their action on the tumor cell proliferation, metabolism, and cellular environment. Some studies have shown an association between obesity and several types of cancer, including breast cancer. There is some evidence that suggests that there is crosstalk between PPARs and leptin during the development of breast cancer. Through a systematic review of previous studies, we have reviewed the published relevant articles regarding leptin signaling in breast cancer and its crosstalk with peroxisome proliferator-activated receptors α and γ.
Topics: Humans; Female; Peroxisome Proliferator-Activated Receptors; Leptin; PPAR alpha; Breast Neoplasms; Obesity; Signal Transduction; Tumor Microenvironment
PubMed: 36348225
DOI: 10.1007/s12094-022-02988-4 -
Pharmaceuticals (Basel, Switzerland) Oct 2022(C.) belongs to the family Ericaceae and can be found in the Iberian Peninsula, especially on the coastal areas facing the Atlantic coast. berries have been used for... (Review)
Review
(C.) belongs to the family Ericaceae and can be found in the Iberian Peninsula, especially on the coastal areas facing the Atlantic coast. berries have been used for centuries in traditional medicine. Recent studies have revealed that not only the berries but also the leaves have relevant antioxidant, antiproliferative, and anti-inflammatory properties, bringing this plant to the forefront of discussion. A systematic review of the literature was carried out to summarize the phenolic compounds and bioactive properties identified in berries and leaves and to search for research gaps on this topic. The search was conducted in three electronic databases (PubMed, SCOPUS, and Web of Science) using PRISMA methodology. The inclusion criteria were the chemical compositions of the berries, leaves, or their extracts and their bioactive properties. The exclusion criteria were agronomic and archaeological research. The number of studies concerning phenolic compounds' composition and the bioactive properties of berries and leaves is still limited (11 articles). However, the variety of polyphenolic compounds identified make it possible to infer new insights into their putative mechanism of action towards the suppression of NF-kB transcription factor activation, the modulation of inflammatory mediators/enzymes, the induction of apoptosis, the modulation of mitogen activated protein kinase, cell cycle arrest, and the reduction of oxidative stress. These factors can be of major relevance concerning the future use of as nutraceuticals, food supplements, or medicines. Nevertheless, more scientific evidence concerning bioactivity is required.
PubMed: 36297345
DOI: 10.3390/ph15101231