Chun-Yin Huang

The APOA1 rs670 (−75 G>A) polymorphism has been implicated in lipid metabolism and susceptibility to metabolic syndrome (MetS). However, individual studies have reported inconsistent associations with circulating apolipoprotein A1 (Apo A1) and lipid parameters, and no meta-analysis has comprehensively evaluated these associations stratified by metabolic disorder status. We therefore quantified the associations between APOA1 rs670 and serum Apo A1 and lipid parameters, and determined whether these associations are modified by metabolic disorder status. PubMed, Embase, Web of Science, Cochrane Library, and ClinicalTrials.gov were searched from inception to March 2026. Eligible studies reported APOA1 rs670 genotype data with quantitative lipid measurements. Forty studies involving 22,175 participants met the inclusion criteria. Pooled effect sizes were estimated as standardized mean differences (SMDs) with 95% confidence intervals (CIs) using random-effects models. This review was registered in PROSPERO (CRD420261333145). A allele carriers had significantly higher serum Apo A1 (SMD, 0.20; p < 0.001) and HDL-C levels (SMD, 0.14; p < 0.001) than GG homozygotes. Subgroup analyses stratified by metabolic disorder status revealed that the associations with Apo A1 (SMD, 0.53 vs. 0.11) and HDL-C (SMD, 0.23 vs. 0.08) were substantially stronger among individuals with metabolic disorders than among metabolically healthy individuals. No significant associations were observed for LDL-C or triglyceride levels. The APOA1 rs670 polymorphism is associated with higher circulating Apo A1 and HDL-C levels, with stronger associations in individuals with metabolic disorders. These findings suggest that metabolic status modifies the phenotypic effects of rs670 on the Apo A1–HDL pathway.

Background Diastasis recti abdominis (DRA), commonly occurring in postpartum women, is not only an aesthetic issue but is also highly associated with functional impairments. Various conservative treatment modalities have been employed in clinical practice to alleviate DRA. However, the comparative efficacy of these non-surgical treatments for improving the inter-recti distance (IRD) remains to be determined. Aim This current network meta-analysis (NMA) aims to compare the efficacy and acceptability of different non-surgical treatments with or without exercise for improving DRA in postpartum women. Methods This NMA adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. ClinicalKey, Cochrane Library, CINAHL, Embase, PubMed, Web of Science, and ClinicalTrials.gov were systematically searched for randomized controlled trial (RCT) studies up to April 2024. The analysis included studies that met the following criteria: (1) postpartum women diagnosed with DRA defined as an IRD greater than 2 cm; (2) intervention: any non-surgical treatments for at least 2 weeks; (3) comparator: no-treatment control; and (4) outcome: changes in IRD and acceptability. The relative efficacy between the non-surgical treatments tested and the probability of treatments were evaluated. Results Twenty-one RCTs comprising 1195 participants aged from 18 to 45 years old were included. The forest plot revealed that exercise coupling with neuromuscular electrical stimulation systems (NMES) [mean difference (MD) − 1.12 cm, 95% confidence interval (CI) − 1.66 to − 0.58], acupuncture (MD − 0.81 cm, 95% CI − 1.54 to − 0.08), corset (MD − 0.65 cm, 95% CI − 1.24 to − 0.06), and exercise alone (MD − 0.48 cm, 95% CI − 0.80 to − 0.16) led to significant reductions in IRD compared with control. Further, the treatment ranking indicated that the combination of NMES with exercise has the highest probability (91.0%) of being the best treatment for reducing IRD, followed by acupuncture with exercise (71.1%). Treatments combined with exercise demonstrated better rankings for reducing IRD than individual treatments without exercise. Acceptability did not significantly differ between the groups. Limitations and Implications This NMA encountered limitations due to participant variability, differing measurement methods, and sparse data, necessitating careful interpretation of findings regarding postpartum DRA interventions. Conclusions This NMA suggests NMES combined with exercise as the best treatment tested for DRA in postpartum women. PROSPERO Registration CRD42024541345.

By Chien-Yi Chan, Chia-Hsien Lien, Ming-Fen Lee, et al., Published on

Aim: To explore the link between the RBP4 rs3758539 genotype and metabolic syndrome risk factors and whether the impact of this genetic variation displays any potential race discrepancy. Materials and Methods: This meta‐analysis followed the PRISMA guidelines and was registered with PROSPERO (registration no. CRD42023407999). PubMed, Web of Science, Embase, Cochrane Library, Google Scholar, Airiti Library and CINAHL databases were used for the study search until October 2023. We evaluated the methodological quality using the Joanna Briggs Institute checklist and determined the correlation using a random‐effects meta‐analysis. Results: The results indicated that individuals with the rs3758539 GA/AA genotype had a higher risk profile, including lower high‐density lipoprotein levels [correlation: −0.045, 95% confidence interval (CI): −0.080 to −0.009, p = .015, I ² = 46.9%] and higher body mass index (correlation: 0.117, 95% CI: 0.036‐0.197, p = .005, I ² = 82.0%), body fat (correlation: 0.098, 95% CI: 0.004‐0.191, p = .041, I ² = 64.0%), and low‐density lipoprotein levels (correlation: 0.074, 95% CI: 0.010‐0.139, p = .024, I ² = 0%), of developing metabolic syndrome than those with the GG genotype. The subgroup analysis maintained a significantly positive correlation between the rs3758539 GA/AA genotype and body mass index (correlation: 0.163, 95% CI: 0.031‐0.289, p = .016, I ² = 88.9%) but a negative correlation with high‐density lipoprotein levels (correlation: −0.047, 95% CI: −0.087 to −0.006, p = .025, I ² = 65.7%) in the Asian group only. Conclusion: The current meta‐analysis supports a significant link between the RBP4 rs3758539 GA/AA genotype and the metabolic syndrome.

Oral squamous cell carcinoma (OSCC) frequently carries high epidermal growth factor receptor (EGFR) expression. Erlotinib, a small molecule tyrosine kinase inhibitor (TKI), is an effective inhibitor of EGFR activity; however, resistance to this drug can occur, limiting therapeutic outcomes. Therefore, in the current study, we aimed to unveil key intracellular molecules and adjuvant reagents to overcome erlotinib resistance. First, two HSC-3-derived erlotinib-resistant cell lines, ERL-R5 and ERL-R10, were established; both exhibited relatively higher growth rates, glucose utilization, epithelial-mesenchymal transition (EMT), and invasiveness compared with parental cells. Cancer aggressiveness-related proteins, such as N-cadherin, Vimentin, Twist, MMP-2, MMP-9, and MMP-13, and the glycolytic enzymes PKM2 and GLUT1 were upregulated in ERL-R cells. Notably, ERL-R cells were sensitive to quercetin, a naturally-existing flavonol phytochemical with anti-cancer properties against various cancer cells. At a concentration of 5 μM, quercetin effectively arrested cell growth, reduced glucose utilization, and inhibited cellular invasiveness. An ERL-R5-derived xenograft mouse model confirmed the growth-inhibitory efficacy of quercetin. Additionally, knock-down of PKM2 by siRNA mimicked the effect of quercetin and re-sensitized ERL-R cells to erlotinib. Furthermore, adding quercetin blocked the development of erlotinib-mediated resistance by enhancing apoptosis. In conclusion, our data support the application of quercetin in anti-erlotinib-resistant OSCC and indicate that PKM2 is a determinant factor in erlotinib resistance and quercetin sensitivity.

Increasing lines of evidence indicate that the biologically active form of vitamin D, calcitriol (1,25-dihydroxyvitamin D₃), prevents cancer progression by reducing cell proliferation, increasing cell differentiation, and inhibiting angiogenesis, among other potential roles. Cancer cells in solid tumors preferably undergo the “Warburg effect” to support cell growth by upregulating glycolysis, and the glycolytic intermediates further serve as building blocks to generate biomass. The objective of the current study is to investigate whether calcitriol affects glucose metabolism and cell growth in human colorectal cancer cells. Calcitriol reduced the expression of cyclin D1 and c-Myc. In addition, calcitriol reduced the expression of glucose transporter 1 (GLUT1) and key glycolytic enzymes and decreased extracellular acidification rate but increased oxygen consumption rate in human colorectal cancer cells. In a subcutaneous HT29 xenograft NOD/SCID mouse model, the volume and weight of the tumors were smaller in the calcitriol groups as compared with the control group, and the expression levels of GLUT1 and glycolytic enzymes, hexokinase 2 and lactate dehydrogenase A, were also lower in the calcitriol groups in a dose-responsive manner. Our data indicate that calcitriol suppresses glycolysis and cell growth in human colorectal cancer cells, suggesting an inhibitory role of the biologically active form of vitamin D in colorectal cancer progression.

Background: Epidermal growth factor receptor (EGFR) is often hyperactivated in head and neck squamous cell carcinoma (HNSCC); however, its downstream mediators are not fully identified. Here, we investigate the role of transcription factor HBP1 in the anticancer efficacy of EGFR inhibitor erlotinib in HNSCC.Methods: The effect of erlotinib and HBP1 on cell proliferation and invasion was examined by flow cytometric analysis and a Matrigel invasion assay, respectively. Oral tumor specimens were used to evaluate the association between the expression level of EGFR and HBP1, and metastatic potential.Results: Erlotinib caused cell growth arrest in the G1 phase and sluggish invasion with a concomitant increase in HBP1 and p27 expression. The erlotinib effect was attenuated upon HBP1 knockdown. Analysis of oral tumor specimens revealed that the low HBP1/high EGFR status can predict metastatic potential.Conclusions: Our data support HBP1 as a crucial mediator of EGFR‐targeting inhibitors in HNSCC.

Non‐small‐cell lung cancer (NSCLC) accounts for the majority of the lung cancer cases that have become a leading cause of cancer deaths worldwide. Overexpression of transcription factor forkhead box M1 (FOXM1) is involved in the inauspicious development of several types of cancer, including lung tumor aggressiveness. Our laboratory has previously found that MED28, a Mediator subunit for transcriptional activation, modulates cell growth, epithelial‐mesenchymal transition, migration, and invasion in human breast cancer cells. The objective of the current study is to investigate the potential role of MED28 and FOXM1 in NSCLC. In addition to A549 and PC9 cells, we also used a doxycycline‐inducible system to generate FOXM1‐overexpressed A549‐DN cells, and we explored the connection of MED28 with FOXM1 and their effect on migration. Herein, we report that the increased expression levels of both MED28 and FOXM1 elevated the expression of matrix metalloproteinase 2 (MMP2), a metastasis marker, which enhanced cell migration and matrigel invasion of NSCLC cells. Furthermore, MED28 interacted with FOXM1, and both exhibited a mutual effect on the expression and subcellular localization. Moreover, MED28 small interfering RNA‐mediated MMP2 gene suppression could be attenuated by inducible expression of a constitutively active form of FOXM1, which consequently restored the migration and invasion ability of NSCLC cells. Our data indicate that MED28 interacts with FOXM1, and each affects the expression and localization of the other, and, more importantly, both regulate MMP2‐dependent migration and invasion in human lung cancer cells.

Transcription factor high‐mobility group box‐containing protein 1 (HBP1) may function as a tumor suppressor in various types of cancer. In a previous study, we demonstrated that HBP1 suppressed cell invasion in oral cancer. To further understand the underlying mechanism, the current study is aimed at investigating how HBP1 exerts its antimetastatic potential in oral cancer. In a cell model, ectopic expression of HBP1 potently suppressed epithelial–mesenchymal transition, cellular migration, and invasion; conversely, HBP1 knockdown promoted these malignant phenotypes. The matrix metalloproteinase (MMP) family is highly implicated in tumor metastasis. Therefore, we examined the effect of HBP1 on the activation of the MMP members, MMP‐2, ‐9, and ‐13 that are highly associated with the aggressiveness of oral cancer. Ectopic expression of HBP1 resulted in a mild reduction in the expression and activity of MMP‐2 and ‐9, yet it had a potent inhibitory effect on MMP‐13. In contrast, HBP1 knockdown strongly enhanced the activation of MMP‐13. Further, we demonstrated that MMP‐13 is a target of HBP1 transcription repression as evidenced by the identification of an HBP1 binding site in the cis proximal region of the MMP‐13 promoter. More important, MMP‐13 knockdown significantly alleviated HBP1 small interfering RNA‐mediated promotion in cell invasion. Analysis of oral tumor specimens revealed that the low HBP1 (3‐fold) status was associated with metastatic potential. All told, our study provides evidence supporting the idea that the HBP1–MMP‐13 axis is a key regulator of the aggressiveness in oral cancer.