-
Molecular Biology Reports Dec 2023Today, modern lifestyles and disrupted sleep patterns cause circadian clock rhythm impairments that are associated with altered leptin levels, which subsequently affect... (Review)
Review
BACKGROUND
Today, modern lifestyles and disrupted sleep patterns cause circadian clock rhythm impairments that are associated with altered leptin levels, which subsequently affect a wide range of physiological processes and have significant health burdens on societies. Nevertheless, there has been no systematic review of circadian clock genes and proteins, leptin, and related signaling pathways.
METHODS
Accordingly, we systematically reviewed circadian clock proteins, leptin, and molecular mechanisms between them by searching Pubmed, Scopus, ProQuest, Web of Sciences, and Google Scholar until September 2022. After considering the inclusion and exclusion criteria, 20 animal studies were selected. The risk of bias was assessed in each study.
RESULTS
The results clarified the reciprocal interconnected relationship between circadian clock genes and leptin. Circadian clock genes regulate leptin expression and signaling via different mechanisms, such as CLOCK-BMAL1 heterodimers, which increase the expression of PPARs. PPARs induce the expression of C/EBPα, a key factor in upregulating leptin expression. CLOCK-BMAL1 also induces the expression of Per1 and Rev-erb genes. PER1 activates mTORC1 and mTORC1 enhances the expression of C/EBPα. In addition, REV-ERBs activate the leptin signaling pathway. Also, leptin controls the expression of circadian clock genes by triggering the AMPK and ERK/MAPK signaling pathways, which regulate the activity of PPARs. Moreover, the roles of these molecular mechanisms are elucidated in different physiological processes and organs.
CONCLUSIONS
Crosstalk between circadian clock genes and leptin and their affecting elements should be considered in the selection of new therapeutic targets for related disorders, especially obesity and metabolic impairments.
Topics: Animals; ARNTL Transcription Factors; Circadian Clocks; Circadian Rhythm; Circadian Rhythm Signaling Peptides and Proteins; Leptin; Mechanistic Target of Rapamycin Complex 1; Nuclear Receptor Subfamily 1, Group D, Member 1; Peroxisome Proliferator-Activated Receptors; Humans
PubMed: 37874505
DOI: 10.1007/s11033-023-08887-3 -
Journal of Ocular Pharmacology and... Nov 2023Currently, corneal blindness is affecting >10 million individuals worldwide, and there is a significant unmet medical need because only 1.5% of transplantation needs are... (Review)
Review
Currently, corneal blindness is affecting >10 million individuals worldwide, and there is a significant unmet medical need because only 1.5% of transplantation needs are met globally due to a lack of high-quality grafts. In light of this global health disaster, researchers are developing corneal substitutes that can resemble the human cornea and replace human donor tissue. Thus, this review examines ROCK (Rho-associated coiled-coil containing protein kinases) inhibitors as a potential corneal wound-healing (CWH) therapy by reviewing the existing clinical and nonclinical findings. The systematic review was done from PubMed, Scopus, Web of Science, and Google Scholar for CWH, corneal injury, corneal endothelial wound healing, ROCK inhibitors, Fasudil, Netarsudil, Ripasudil, Y-27632, clinical trial, clinical study, case series, case reports, preclinical study, , and studies. After removing duplicates, all downloaded articles were examined. The literature search included the data till January 2023. This review summarized the results of ROCK inhibitors in clinical and preclinical trials. In a clinical trial, various ROCK inhibitors improved CWH in individuals with open-angle glaucoma, cataract, iris cyst, ocular hypertension, and other ocular diseases. ROCK inhibitors also improved ocular wound healing by increasing cell adhesion, migration, and proliferation and . ROCK inhibitors have antifibrotic, antiangiogenic, anti-inflammatory, and antiapoptotic characteristics in CWH, according to the existing research. ROCK inhibitors were effective topical treatments for corneal infections. Ripasudil, Y-27632, H-1152, Y-39983, and AMA0526 are a few new ROCK inhibitors that may help CWH and replace human donor tissue.
Topics: Humans; Endothelium, Corneal; Glaucoma, Open-Angle; Corneal Injuries; Corneal Transplantation; rho-Associated Kinases
PubMed: 37738326
DOI: 10.1089/jop.2023.0040 -
Drug Development Research Aug 2023This study aims to assess studies on circular RNAs (circRNAs) in the chemoresistance of triple-negative breast cancer (TNBC) and provide relevant references for the... (Review)
Review
This study aims to assess studies on circular RNAs (circRNAs) in the chemoresistance of triple-negative breast cancer (TNBC) and provide relevant references for the development of new TNBC chemotherapy sensitivity biomarkers and therapeutic targets. The PubMed, Embase, Web of Knowledge, Cochrane Library, and four Chinese databases were searched up to January 27, 2023, and studies related to TNBC chemoresistance were included. The basic characteristics of the studies and the mechanisms of circRNAs in regulating TNBC chemoresistance were analyzed. A total of 28 studies published between 2018 and 2023 were included, and the chemotherapeutics included adriamycin, paclitaxel, docetaxel, 5-fluorouracil, lapatinib, and so forth. A total of 30 circRNAs were identified, 86.67% (n = 26) of these circRNAs were reported to act as microRNA (miRNA) sponges to regulate chemotherapy sensitivity, while only two circRNAs (circRNA-MTO1 and circRNA-CREIT) interacted with proteins. A total of 14, 12, and 2 circRNAs were reported to be associated with chemoresistance to adriamycin, taxanes, and 5-fluorouracil, respectively. Six circRNAs were found to act as miRNA sponges that promote chemotherapy resistance by regulating the PI3K/Akt signalling pathway. CircRNAs participate in the regulation of TNBC chemoresistance and can be used as biomarkers and therapeutic targets for improving chemotherapy sensitivity. However, further studies are needed to confirm the role of circRNAs in TNBC chemoresistance.
Topics: Humans; RNA, Circular; Triple Negative Breast Neoplasms; Drug Resistance, Neoplasm; Phosphatidylinositol 3-Kinases; MicroRNAs; Biomarkers; Doxorubicin; Fluorouracil; Gene Expression Regulation, Neoplastic
PubMed: 37114737
DOI: 10.1002/ddr.22069 -
Urologia Feb 2024The major barriers to phytonutrients in prostate cancer therapy are non-specific mechanisms and bioavailability issues. Studies have pointed to a synergistic combination... (Review)
Review
The major barriers to phytonutrients in prostate cancer therapy are non-specific mechanisms and bioavailability issues. Studies have pointed to a synergistic combination of curcumin (CURC) and ursolic acid (UA). We investigate this combination using a systematic review process to assess the most likely mechanistic pathway and human testing in prostate cancer. We used the PRISMA statement to screen titles, abstracts, and the full texts of relevant articles and performed a descriptive analysis of the literature reviewed for study inclusion and consensus of the manuscript. The most common molecular and cellular pathway from articles reporting on the pathways and effects of CURC ( = 173) in prostate cancer was NF-κB ( = 25, 14.5%). The most common molecular and cellular pathway from articles reporting on the pathways and effects of UA ( = 24) in prostate cancer was caspase 3/caspase 9 ( = 10, 41.6%). The three most common molecular and cellular pathway from articles reporting on the pathways and effects of both CURC and UA ( = 193) in prostate cancer was NF-κB ( = 28, 14.2%), Akt ( = 22, 11.2%), and androgen ( = 19, 9.6%). Therefore, we have identified the potential synergistic target pathways of curcumin and ursolic acid to involve NF-κB, Akt, androgen receptors, and apoptosis pathways. Our review highlights the limited human studies and specific effects in prostate cancer.
Topics: Male; Humans; Ursolic Acid; Curcumin; NF-kappa B; Signal Transduction; Proto-Oncogene Proteins c-akt; Apoptosis; Triterpenes; Prostatic Neoplasms
PubMed: 37776274
DOI: 10.1177/03915603231202304 -
Critical Reviews in Oncology/hematology Jun 2024This systematic review summarizes evidence of VEGFR gene mutations and VEGF/VEGFR protein expression in glioblastoma multiforme (GBM) patients, alongside the efficacy... (Review)
Review
PURPOSE
This systematic review summarizes evidence of VEGFR gene mutations and VEGF/VEGFR protein expression in glioblastoma multiforme (GBM) patients, alongside the efficacy and safety of anti-VEGFR tyrosine kinase inhibitors (TKIs) for GBM treatment.
METHODS
A comprehensive literature review was conducted using PubMed up to August 2023. Boolean operators and MeSH term "glioma," along with specific VEGFR-related keywords, were utilized following thorough examination of existing literature.
RESULTS
VEGFR correlates with glioma grade and GBM progression, presenting a viable therapeutic target. Regorafenib and axitinib show promise among studied TKIs. Other multi-targeted TKIs (MTKI) and combination therapies exhibit potential, albeit limited by blood-brain barrier penetration and toxicity. Combining treatments like radiotherapy and enhancing BBB penetration may benefit patients. Further research is warranted in patient quality of life and biomarker-guided selection.
CONCLUSION
While certain therapies hold promise for GBM, future research should prioritize personalized medicine and innovative strategies for improved treatment outcomes.
Topics: Humans; Glioblastoma; Protein Kinase Inhibitors; Receptors, Vascular Endothelial Growth Factor; Brain Neoplasms; Antineoplastic Agents
PubMed: 38677355
DOI: 10.1016/j.critrevonc.2024.104365 -
European Journal of Cancer (Oxford,... May 2024The first-line treatment choice of EGFRIs plus doublet chemotherapy vs. bevacizumab plus doublet chemotherapy remains a topic of interest for patients with left-sided... (Meta-Analysis)
Meta-Analysis Review
A meta-analysis of efficacy and safety data from head-to-head first-line trials of epidermal growth factor receptor inhibitors versus bevacizumab in adult patients with RAS wild-type metastatic colorectal cancer by sidedness.
The first-line treatment choice of EGFRIs plus doublet chemotherapy vs. bevacizumab plus doublet chemotherapy remains a topic of interest for patients with left-sided RAS WT mCRC. We conducted a systematic literature review and meta-analysis of clinical trial data published between 2015 and 2024. We evaluated the relative efficacy and safety of first-line EGFRIs plus doublet chemotherapy (FOLFIRI or FOLFOX) vs. bevacizumab plus doublet chemotherapy for patients with RAS WT left-sided mCRC, as well as in all- and right-sided tumors. We identified eight trials with 2624 patients. Five trials reported outcomes by tumor sidedness. In the left-sided population, overall survival (OS) (Hazard Ratio (HR) = 0.80, 95% Confidence Interval (CI): 0.71-0.90) and objective response rate (ORR) (Odds ratio [OR]=1.61, 95% CI: 1.30-1.99) favored EGFRI plus chemotherapy, while no statistically significant differences were observed for progression-free survival (PFS) (HR=0.93, 95% CI: 0.84-1.04) or resection rate (RR). Similar results were found in the all-sided population. In the right-sided population, PFS favored bevacizumab plus chemotherapy (HR=1.45, 95% CI: 1.19-1.78), while no statistically significant differences were observed for OS (HR=1.17, 95% CI: 0.95-1.44), ORR (OR=0.99, 95% CI: 0.69-1.41), and RR. Early tumor shrinkage in the all-sided population favored EGFRI plus chemotherapy (OR=1.72; 95% CI: 1.36-2.17); limited data precluded evaluation by sidedness. Safety was available in 6 trials for all-sided tumors and 1 trial for left-sided tumors, each demonstrating typical class-specific adverse events. This most comprehensive meta-analysis indicates a benefit for first-line EGFRI plus chemotherapy over bevacizumab plus chemotherapy in patients with left-sided RAS WT mCRC.
Topics: Adult; Humans; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Colorectal Neoplasms; ErbB Receptors
PubMed: 38442645
DOI: 10.1016/j.ejca.2024.113975 -
Gene Sep 2023In recent years, the results of the association between Tribbles Pseudokinase 1 (TRIB1) gene polymorphism and the risk of coronary artery disease (CAD) and stroke are... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND AIMS
In recent years, the results of the association between Tribbles Pseudokinase 1 (TRIB1) gene polymorphism and the risk of coronary artery disease (CAD) and stroke are inconsistent. This study aimed to systematically review the literature on TRIB1 gene polymorphisms and susceptibility to coronary atherosclerotic heart disease (CAD) and stroke.
METHODS
This study collected studies published until May 2022 through a systematic search of PubMed, Web of Science, and Google Scholar databases. After a systematic literature search, pooled odds ratio (OR) and their corresponding 95 % confidence interval (CI) were used to assess the strength of the association.
RESULTS
We identified 6 studies on rs17321515, including 12,892 controls and 4583 patients, and 3 on rs2954029, including 1732 controls and 1305 patients. In different genetic models, the rs2954029 genetic polymorphism significantly increased the risk of CAD and stroke. In the codominant model, the AA genotype increased the risk of CAD and stroke (OR = 1.74, 95 % CI = 1.39-2.17, P < 0.001); the TA genotype also increased the prevalence of CAD and stroke risk (OR = 1.39, 95 % CI = 1.18-1.64, P < 0.001). Compared with the control group, the TT + TA genotype increased the risk of CAD and stroke in the dominant genetic model (OR = 1.46, 95 %CI = 1.25-1.71, P < 0.001), and in the recessive model, the TA + AA genotype increased the risk of CAD and stroke (OR = 1.41, 95 % CI = 1.15-1.72, P < 0.001). In addition, the TRIB1 rs17321515 polymorphism was not found to be associated with the risk of CAD and stroke, which may be related to other factors such as race.
CONCLUSIONS
The rs2954029 A allele was significantly associated with an increased risk of CAD and stroke, according to the present meta-analysis. However, the association of rs17321515 polymorphism with susceptibility to CAD and stroke has not been found in this study.
Topics: Humans; Coronary Artery Disease; Genetic Predisposition to Disease; Polymorphism, Single Nucleotide; Genotype; Stroke; Protein Serine-Threonine Kinases; Intracellular Signaling Peptides and Proteins
PubMed: 37414350
DOI: 10.1016/j.gene.2023.147613 -
Journal of Racial and Ethnic Health... Feb 2024Ameloblastoma is an aggressively growing jaw tumor with high recurrent properties. Reports on global and racial distribution of ameloblastoma are variable and... (Meta-Analysis)
Meta-Analysis Review
Ameloblastoma is an aggressively growing jaw tumor with high recurrent properties. Reports on global and racial distribution of ameloblastoma are variable and inconclusive. The role of race and ethnicity on ameloblastoma growth characteristics, genetic mutational profile, and recurrence is also still unclear. The primary aim of this systematic review was to assess genetic, racial, and ethnic distribution of primary and recurrent ameloblastoma from published literature. The secondary aim was to assess potential correlations between ethnicity, genetic mutation, and disparities in ameloblastoma treatment outcomes in Afro-descendants and non-Afro-descendants. Twenty-three eligible articles were selected based on preferred reporting items for systematic review and meta-analysis (PRISMA), and a total of 169 ameloblastoma cases were evaluated. Data on patient demographics, ameloblastoma growth characteristics, and genetic status were collected for quantitative analysis. Among a total of 169 ameloblastoma cases, Afro-descendant patients had higher primary and recurrent ameloblastomas at 15.5% and 4.7% respectively compared to non-Afro-descendant at 10.7% and 1.8% respectively. Additionally, BRAF V600E was positively associated with 48.8% of all ameloblastomas and strong predilection for Afro-descendants. Despite the paucity of information on genetic profile of ameloblastomas in the Afro-descendant patient cohort, this ethnic group still accounted for 2.95% of all BRAF V600E-positive tumors. These suggest that Afro-descendants are understudied regarding ameloblastoma characteristics, genetic profile, and recurrence profile. Mutational analysis of ameloblastoma tumors in Afro-descendants should be promoted.
Topics: Humans; Ameloblastoma; Proto-Oncogene Proteins B-raf; Jaw Neoplasms; Treatment Outcome; Mutation
PubMed: 36596981
DOI: 10.1007/s40615-022-01500-6 -
BMC Ophthalmology Nov 2023To evaluate the efficacy of anti-vascular endothelial growth factor (VEGF) in treatment of age-related macular degeneration (AMD) with retinal pigment epithelial... (Meta-Analysis)
Meta-Analysis
Comparative efficacy of aflibercept and ranibizumab in the treatment of age-related macular degeneration with retinal pigment epithelial detachment: a systematic review and network meta-analysis.
OBJECTIVES
To evaluate the efficacy of anti-vascular endothelial growth factor (VEGF) in treatment of age-related macular degeneration (AMD) with retinal pigment epithelial detachment (PED).
METHODS
Systematic review identifying studies comparing intravitreal ranibizumab (IVR), intravitreal aflibercept (IVA) and intravitreal conbercept (IVC) published before Mar 2022.
RESULTS
One randomized controlled trial and 6 observational studies were selected for meta-analysis (1,069 patients). The change of best corrected visual acuity (BCVA) in IVA 2.0 mg group was better than IVR 0.5 mg (average difference 0.07) and IVR 2.0 mg (average difference 0.10), the differences were statistically significant. The change of the height of PED in IVA 2.0 group was better than IVR 0.5 group (average difference 45.30), the difference was statistically significant. The proportion of patients without PED at last visit in IVA 2.0 group were better than those in IVR 2.0 group (hazard ratio 1.91), the difference was statistically significant. There was no significant difference compared with IVR 0.5 group (hazard ratio 1.45). IVA required fewer injections than IVR, with a mean difference of -1.58.
CONCLUSIONS
IVA appears to be superior to IVR in improvement of BCVA, height decrease of PED and regression of PED with less injections in nAMD with PED.
Topics: Humans; Ranibizumab; Angiogenesis Inhibitors; Retinal Detachment; Network Meta-Analysis; Vascular Endothelial Growth Factor A; Retinal Pigment Epithelium; Retrospective Studies; Receptors, Vascular Endothelial Growth Factor; Recombinant Fusion Proteins; Intravitreal Injections; Macular Degeneration
PubMed: 37990182
DOI: 10.1186/s12886-023-03214-7 -
BMC Cancer Oct 2023N-myc downstream-regulated gene-1 (NDRG1) is well-described as a potent metastasis suppressor, but its role in human breast cancer remains controversial and unclear.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
N-myc downstream-regulated gene-1 (NDRG1) is well-described as a potent metastasis suppressor, but its role in human breast cancer remains controversial and unclear. Therefore, the present study utilized a systematic review and meta-analysis approach to synthesize the association between NDRG1 protein expression and the aggressive characteristics of breast cancer.
METHODS
The protocol for the systematic review and meta-analysis was registered on the PROSPERO website (CRD42023414814). Relevant articles were searched for in PubMed, Scopus, Embase, MEDLINE, and Ovid between March 30, 2023, and May 5, 2023. The included studies were critically evaluated using the Joanna Briggs Institute critical appraisal tools. The results from individual studies were qualitatively synthesized using textual narrative synthesis. Using a random-effects model, the pooled log odds ratio of effect estimate was used to look at the link between NDRG1 protein expression and aggressive features of breast cancer, such as tumor grade, tumor stage, metastasis to the axillary lymph nodes, and hormonal receptor status.
RESULTS
A total of 1423 articles were retrieved from the electronic database search, and six studies that met the eligibility criteria were included for synthesis. There was an association between the expression of NDRG1 protein and the status of the axillary lymph nodes (P = 0.01, log Odds Ratio (OR): 0.59, 95% Confidence Interval (CI): 0.13-1.05, I: 24.24%, 292 breast cancer cases with positive axillary lymph nodes and 229 breast cancer cases with negative axillary lymph nodes, 4 studies). NDRG1 protein expression and human epidermal growth factor receptor 2 (Her2) status were found to have a negative relationship (P = 0.01, log OR: -0.76, 95% CI: -1.32-(-0.20), I: 32.42%, 197 breast cancer cases with Her2 positive and 272 breast cancer cases with Her2 negative, 3 studies). No correlation was found between NDRG1 protein expression and tumor grade (P = 0.10), estrogen receptor (ER) status (P = 0.57), or progesterone receptor (PR) status (P = 0.41).
CONCLUSION
The study concluded that increased NDRG1 protein expression was associated with increased metastasis of the tumor to the axillary lymph node. Additionally, increased NDRG1 protein expression was observed in Her2-negative breast cancer, suggesting its role in both less aggressive and more aggressive behavior depending on breast cancer subtypes. Based on the findings of the meta-analysis, an increase in NDRG1 protein expression was associated with aggressive characteristics of breast cancer.
Topics: Female; Humans; Axilla; Breast Neoplasms; Cell Cycle Proteins; Intracellular Signaling Peptides and Proteins; Lymph Nodes; Receptor, ErbB-2; Receptors, Progesterone
PubMed: 37858101
DOI: 10.1186/s12885-023-11517-7