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Pharmacological Research Jan 2024Zinc is a crucial trace element in the human body, playing a role in various physiological processes such as oxidative stress, neurotransmission, protein synthesis, and...
Zinc is a crucial trace element in the human body, playing a role in various physiological processes such as oxidative stress, neurotransmission, protein synthesis, and DNA repair. The zinc transporters (ZnTs) family members are responsible for exporting intracellular zinc, while Zrt- and Irt-like proteins (ZIPs) are involved in importing extracellular zinc. These processes are essential for maintaining cellular zinc homeostasis. Imbalances in zinc metabolism have been linked to the development of neurodegenerative diseases. Disruptions in zinc levels can impact the survival and activity of neurons, thereby contributing to the progression of neurodegenerative diseases through mechanisms like cell apoptosis regulation, protein phase separation, ferroptosis, oxidative stress, and neuroinflammation. Therefore, conducting a systematic review of the regulatory network of zinc and investigating the relationship between zinc dysmetabolism and neurodegenerative diseases can enhance our understanding of the pathogenesis of these diseases. Additionally, it may offer new insights and approaches for the treatment of neurodegenerative diseases.
Topics: Humans; Cation Transport Proteins; Disease Progression; Homeostasis; Neurodegenerative Diseases; Zinc
PubMed: 38123108
DOI: 10.1016/j.phrs.2023.107039 -
Journal of Biomolecular Structure &... Sep 2023Protein subcellular localization is a promising research question in Proteomics and associated fields, including Biological Sciences, Biomedical Engineering,... (Review)
Review
Protein subcellular localization is a promising research question in Proteomics and associated fields, including Biological Sciences, Biomedical Engineering, Computational Biology, Bioinformatics, Proteomics, Artificial Intelligence, and Biophysics. However, computational techniques are preferred to explore this attribute for a massive number of proteins. The byproduct of this conjunction yields diversified location identifiers of proteins. These protein subcellular localization identifiers are unique regarding the database used, organisms, Machine Learning Technique, and accuracy. Despite the availability of these identifiers, the majority of the work has been done on the subcellular localization of proteins and, less work has been done specifically on locations of transmembrane proteins. This systematic review accounts for computational techniques implemented on transmembrane protein localization. Moreover, a literature search on PubMed, Science Direct, and IEEE Databases disclosed no systematic review or meta-analysis on the cell's transmembrane protein locale. A Systematic review was formed under the guidelines of PRISMA by using Science Direct, PubMed, and IEEE Databases. Journal publications from 2000 to 2023 were taken into consideration and screened. This review has focused only on computational studies rather than experimental techniques. 1004 studies were reviewed and were categorized as relevant and non-relevant according to inclusion and exclusion criteria. All the screening was done through Endnote after importing citations. This systematic review characterizes the gap in targeting the locale of the transmembrane protein and will aid researchers in exploring its new horizons.Communicated by Ramaswamy H. Sarma.
PubMed: 37768108
DOI: 10.1080/07391102.2023.2260490 -
Neurochemical Research Dec 2023Xanthones are natural secondary metabolites that possess great potential as neuroprotective agents due to their prominent biological effects on Alzheimer's disease (AD).... (Review)
Review
Xanthones are natural secondary metabolites that possess great potential as neuroprotective agents due to their prominent biological effects on Alzheimer's disease (AD). However, their underlying mechanisms in AD remain unclear. This study aimed to systematically review the effects and mechanisms of xanthones in cell culture and animal studies, gaining a better understanding of their roles in AD. A comprehensive literature search was conducted in the Medline and Scopus databases using specific keywords to identify relevant articles published up to June 2023. After removing duplicates, all articles were imported into the Rayyan software. The article titles were screened based on predefined inclusion and exclusion criteria. Relevant full-text articles were assessed for biases using the OHAT tool. The results were presented in tables. Xanthones have shown various pharmacological effects towards AD from the 21 preclinical studies included. Cell culture studies demonstrated the anti-cholinesterase activity of xanthones, which protects against the loss of acetylcholine. Xanthones exhibited neuroprotective effects by promoting cell viability, reducing the accumulation of β-amyloid and tau aggregation. The administration of xanthones in animal models resulted in a reduction in neuronal inflammation by decreasing microglial and astrocyte burden. In terms of molecular mechanisms, xanthones prevented neuroinflammation through the modulation of signaling pathways, including TLR4/TAK1/NF-κB and MAPK pathways. Mechanisms such as activation of caspase-3 and -9 and suppression of endoplasmic reticulum stress were also reported. Despite the various neuroprotective effects associated with xanthones, there are limited studies reported on their underlying mechanisms in AD. Further studies are warranted to fully understand their potential roles in AD.
Topics: Animals; Alzheimer Disease; Amyloid beta-Peptides; Antioxidants; Neuroprotective Agents; Xanthones
PubMed: 37578655
DOI: 10.1007/s11064-023-04005-8 -
Medicine Jul 2023To investigate the potential active ingredients and possible mechanisms of Shujin Tongluo granules (SJTLG) in the treatment of cervical spondylosis (CS) by network... (Meta-Analysis)
Meta-Analysis
BACKGROUND
To investigate the potential active ingredients and possible mechanisms of Shujin Tongluo granules (SJTLG) in the treatment of cervical spondylosis (CS) by network pharmacology and molecular docking.
METHODS
The active ingredients and potential targets of SJTLG were obtained through databases such as traditional Chinese medicine system (TCMSP) and BATMAN-traditional Chinese medicine (TCM), and the relevant human targets of CS were identified through databases such as OMIM, GeneCards, and DisGeNET. The intersection targets were imported into STRING for protein-protein interaction (PPI) analysis. The obtained data were imported into Cytoscape 3.9.0 software for visualization, and module analysis was performed using the MCODE plug-in. The representative targets were screened through the Metascape website for pathway enrichment analysis in Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Cytoscape software was used to build networks such as "drug-compound-target" and "drug-compound-target-pathway." Finally, the key targets were selected for molecular docking with the corresponding compounds by Autodock Tools 1.5.7 and visualized by PyMol.
RESULTS
A total of 132 active compounds and 996 targets from SJTLG and 678 targets from CS were screened with 116 intersection targets. The key targets were AKT1, GAPDH, ALB, IL-6, TP53, TNF, VEGFA, IL-1β, EGFR, HSP90AA1, ESR1, and JUN. The results of GO and KEGG enrichment analysis showed that the treatment of CS was mainly related to biological processes such as cellular response to nitrogen compound, cellular response to organonitrogen compound, and positive regulation of locomotion, and the targets were mainly focused on pathways in cancer, Kaposi sarcoma-associated herpesvirus infection, PI3K-Akt signaling pathway, lipid, and atherosclerosis. Molecular docking results showed that the minimum binding energy between the core targets and the corresponding compound was <-5.0 kcal·mol-1.
CONCLUSION
This study preliminarily elucidates the potential active ingredients and mechanism of anti-inflammatory, analgesic, microcirculation improvement, vasodilation, osteoporosis inhibition and nerve nutrition effects of SJTLG in the treatment of CS and provides a reference for its clinical application.
Topics: Humans; Drugs, Chinese Herbal; Molecular Docking Simulation; Network Pharmacology; Spondylosis
PubMed: 37478234
DOI: 10.1097/MD.0000000000034030 -
Current Pharmaceutical Biotechnology Jan 2024Ischemia-reperfusion injury (IRI) is a well-known ailment that can disturb organ function.
BACKGROUND
Ischemia-reperfusion injury (IRI) is a well-known ailment that can disturb organ function.
OBJECTIVES
This systematic review study investigated fisetin's effects and possible mechanisms in attenuating myocardial, cerebral, renal, and hepatic IRIs.
METHODS
This systematic review included studies earlier than Sep 2023 by following the PRISMA statement 2020. After determining inclusion and exclusion criteria and related keywords, bibliographic databases, such as Cochrane Library, PubMed, Web of Science, Embase, and Scopus databases, were used to search the relevant studies. Studies were imported in End- Note X8, and the primary information was recorded in Excel.
RESULTS
Fisetin reduced reactive oxygen species (ROS) generation and upregulated antioxidant enzymes, such as superoxide dismutase (SOD), glutathione (GSH), catalase (CAT), and glutathione peroxidase (GPx), in ischemic tissues. Moreover, fisetin can attenuate oxidative stress by activating phosphoinositide-3-kinase-protein kinase B/Akt (PI3K/Akt) and nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathways. Fisetin has been indicated to prevent the activation of several pro-inflammatory signaling pathways, including NF-κB (Nuclear factor kappa-light-chain-enhancer of activated B cells) and MAPKs (Mitogen-activated protein kinases). It also inhibits the production of pro-inflammatory cytokines and enzymes like tumor necrosis factor-a (TNF-α), inducible-NO synthase (iNOS), cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE2), interleukin-1β (IL-1β), IL-1, and IL-6. Fisetin attenuates IRI by improving mitochondrial function, anti-apoptotic effects, promoting autophagy, and preserving tissues from histological changes induced by IRIs.
CONCLUSION
Fisetin, by antioxidant, anti-inflammatory, mitochondrial protection, promoting autophagy, and anti-apoptotic properties, can reduce cell injury due to myocardial, cerebral renal, and hepatic IRIs without any significant side effects.
PubMed: 38310454
DOI: 10.2174/0113892010281821240102105415 -
JTO Clinical and Research Reports Jun 2024The available approved anticancer drugs for Chinese patients are relatively limited because of China's low participation rate in international clinical trials....
Efficacy and Safety of Anti-Programmed Cell Death Protein 1/Programmed Death-Ligand 1 Antibodies Plus Chemotherapy as First-Line Treatment for NSCLC in the People's Republic of China: a Systematic Review and Meta-Analysis.
INTRODUCTION
The available approved anticancer drugs for Chinese patients are relatively limited because of China's low participation rate in international clinical trials. Therefore, a focus on approved anti-programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) drugs in China is needed. This study aims to assess the heterogeneity of anti-PD-1/PD-L1 antibodies manufactured in China (domestic PD-1/PD-L1) and overseas (imported PD-1/PD-L1) when combined with chemotherapy as the first-line treatment of NSCLC.
METHODS
A systematic search was performed using PubMed, EMBASE, and Cochrane Library of publications up to July 13, 2023. Meta-analysis was applied to compare the efficacy and safety profile between anti-PD-1/PD-L1 antibodies plus chemotherapy (PD-1/PD-L1+Chemo) and chemotherapy alone using STATA software. Pooled hazard ratios for progression-free survival and overall survival, odds ratios for objective response rate, and incidence rate of grade greater than or equal to three treatment-related adverse events with 95% confidence intervals were calculated in the domestic group and imported group by a random-effects model, and the heterogeneity between the two estimates was assessed.
RESULTS
There were 14 eligible clinical studies with a total of 3951 patients involved in this analysis, including eight studies of domestic PD-1/PD-L1+Chemo and six studies of imported PD-1/PD-L1+Chemo. The study revealed that there was no significant difference between domestic and imported PD-1/PD-L1+Chemo in overall survival ( = 0.80), progression-free survival ( = 0.53), and incidence rate of grade greater than or equal to three treatment-related adverse events ( = 0.10). Nevertheless, the objective response rate of imported PD-1/PD-L1+Chemo was significantly higher than that of domestic PD-1/PD-L1+Chemo ( = 0.03).
CONCLUSIONS
Domestic anti-PD-1/PD-L1 antibodies plus chemotherapy were found to have comparable efficacy and safety to those combined with imported anti-PD-1/PD-L1 antibodies based on current evidence.
PubMed: 38846810
DOI: 10.1016/j.jtocrr.2024.100678 -
Antioxidants (Basel, Switzerland) Jul 2023Bioactive compounds in berries may scavenge reactive oxygen and nitrogen species by donating electrons to free radicals, thereby protecting DNA, proteins, and lipids... (Review)
Review
Bioactive compounds in berries may scavenge reactive oxygen and nitrogen species by donating electrons to free radicals, thereby protecting DNA, proteins, and lipids from oxidative damage. Evidence shows that berry consumption has beneficial health effects, though it remains unclear whether berries exert a significant impact on oxidative stress in humans. Thus, we performed a systematic review of randomized controlled trials (RCT) to examine the effects of non-acute (more than a single dose and ≥7 days) berry consumption on biomarkers of oxidative stress. Searches were conducted in PubMed, Cochrane Library, and Scopus; results were imported into Covidence for screening and data extraction. The literature search identified 622 studies that were screened, and 131 full-text studies assessed for eligibility. Ultimately, 28 RCTs met the eligibility criteria. Common biomarkers of oxidative stress (antioxidants, DNA damage, isoprostanes, malondialdehyde, and oxidized LDL) were systematically reviewed, and results were reported narratively. Of the approximate 56 oxidative stress biomarkers evaluated in the 28 RCTs, 32% of the biomarkers were reported to have statistically significant beneficial results and 68% of the biomarkers were reported as having no statistically significant differences. More well-designed and longer-term berry RCTs are needed to evaluate biomarkers of oxidative stress.
PubMed: 37507981
DOI: 10.3390/antiox12071443