Association between vitamin D and cardiovascular health in Chinese children and adolescents: Basing on Life's Essential 8.

BACKGROUND AND AIMS: The relationship between vitamin D and cardiovascular health (CVH) in children remains unclear. We aimed to explore the association between vitamin D and CVH metrics using the latest Life's Essential 8 (LE8) among Chinese children and adolescents. METHODS AND RESULTS: A cross-sectional study containing 2680 participants aged 7-18 years (1340 boys and 1340 girls) was performed in South China in 2013. Vitamin D levels were categorized as follows: ≥20 ng/mL (sufficiency), 12 - < 20 ng/mL (inadequacy), and <12 ng/mL (deficiency). The CVH metrics of LE8 was assessed by overall CVH score, health behavior score, health factor score and high CVH, among which the health behaviors included diet, physical activity, nicotine exposure, and sleep health, as well as the health factors contained body mass index, blood lipids, blood glucose, and blood pressure. Different regression models were used to assess the associations between vitamin D levels and CVH metrics of LE8. Results showed that the prevalence of vitamin D deficiency and inadequacy was 7.5% and 44.4%, respectively. Boys had lower levels in overall CVH score, health behavior score, and health factor score than girls. After adjusting for potential confounds, upward trends in diet score, health behavior score, and high CVH were observed with increasing vitamin D levels. CONCLUSION: Vitamin D levels were positively associated with high CVH based on LE8, and more attention should be paid on boys due to whose lower levels in CVH metrics.

Autophagy Deficiency Induced by SAT1 Potentiates Tumor Progression in Triple-Negative Breast Cancer.

Aggressive triple-negative breast cancer (TNBC) still lacks approved targeted therapies, requiring more exploration of its underlying mechanisms. Previous studies have suggested a potential role of SAT1 (Spermidine/Spermine N1-acetyltransferase 1) in cancer, which needs to be further elucidated in breast cancer. In this study, highly expressed SAT1 in TNBC signified worse patient prognoses. And SAT1 knockdown effectively inhibited the proliferation and migration abilities of TNBC cells in vitro and in vivo. In terms of mechanism, the transcription factor JUN enhanced SAT1 transcriptional activity by binding to its promoter region. Then, SAT1 protein in the cytoplasm engaged in directly binding with YBX1 for sustaining YBX1 protein stability via deubiquitylation mediated by the E3 ligase HERC5. Further, SAT1 was found to suppress autophagy remarkably via stabilization of mTOR mRNA with the accumulation of YBX1-mediated methyl-5-cytosine (m5C) modification. These findings proved that SAT1 drives TNBC progression through the SAT1/YBX1/mTOR axis, which may provide a potential candidate for targeted therapy in advanced TNBC.

The therapeutic potential of circular RNA in triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is among the most aggressive subtypes of the disease that does not express estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2. Circular RNAs (circRNAs) are a type of non-coding RNA with a circular shape formed by non-standard splicing or reverse splicing. Numerous circRNAs exhibit abnormal expression in various malignancies, showing their critical role in the emergence and growth of tumors. Recent studies have shown evidence supporting the idea that certain circRNAs regulate the proliferation and metastasis of TNBC. In addition, circRNAs alter metabolism and the immune microenvironment to promote or inhibit the development of TNBC. Notably, circRNAs may affect the efficacy of clinical drug therapy, serve as therapeutic targets, and be used as molecular biomarkers in the future. Herein, we will first summarize the biogenesis and function of circRNAs. Then, we will explain current research on circRNAs related to TNBC and their potential to serve as therapeutic targets or biomarkers for future drug development, providing a new direction and idea for TNBC therapy.

Interleukin-33 increases the sensitivity of multiple myeloma cells to the proteasome inhibitor bortezomib through reactive oxygen species-mediated inhibition of nuclear factor kappa-B signal and stemness properties.

The proteasome inhibitor bortezomib (BTZ) is the first-line therapy for multiple myeloma (MM). BTZ resistance largely limits its clinical application in MM. Interleukin-33 (IL-33) exerts antitumor effects through various mechanisms, including enhancing antitumor immunity and promoting the apoptosis of cancer cells. Here, the synergistic anti-MM effect of IL-33 and BTZ was verified, and the underlying mechanisms were elucidated. Bioinformatic analysis indicated that IL-33 expression levels were downregulated in MM, and that BTZ-treated MM patients with high IL-33 levels had better prognosis than those with low IL-33 levels. Moreover, the patients with high IL-33 levels had a better treatment response to BTZ. Further immune analysis suggested that IL-33 can enhance the anti-MM immunity. IL-33 and BTZ synergistically inhibited proliferation and induced apoptosis of MM cells, which was mediated by the excessive accumulation of cellular reactive oxygen species (ROS). Furthermore, increased ROS hindered the nuclear translocation of NF-κB-p65, thereby decreasing the transcription of target stemness-related genes (SOX2, MYC, and OCT3/4). These effects induced by the combination therapy could be reversed by eliminating ROS by N-acetylcysteine. In conclusion, our results indicated that IL-33 enhanced the sensitivity of MM to BTZ through ROS-mediated inhibition of nuclear factor kappa-B (NF-κB) signal and stemness properties.

Short-term efficacy and safety of neoadjuvant pyrotinib plus taxanes for early HER2-positive breast cancer: a single-arm exploratory phase II trial.

Background: The effectiveness and safety of pyrotinib have been substantiated in human epidermal growth factor receptor 2 (HER2)-positive advanced breast cancer (BC). However, the role of pyrotinib as a single HER2 blockade in neoadjuvant setting among BC patients has not been studied. The objective of this study was to evaluate the efficacy and tolerability of pyrotinib plus taxanes as a novel neoadjuvant regimen in patients with HER2-positive early or locally advanced BC. Methods: In this single-arm exploratory phase II trial, patients with treatment-naïve HER2-positive BC (stage IIA-IIIC) received pyrotinib 400 mg once daily and taxanes [docetaxel 75 mg/m2 or nanoparticle albumin-bound (nab)-paclitaxel 260 mg/m2 every 3 weeks, or paclitaxel 80 mg/m2 weekly] for a total of four 21-day cycles before surgery. Efficacy assessment was based on pathological and clinical measurements. The primary endpoint of this study was the total pathological complete response (tpCR) rate. The secondary endpoints included breast pCR (bpCR) rate, investigator-assessed objective response rate (ORR) and adverse events (AEs) profiles. Results: From 1 September 2021 to 30 December 2022, a total of 31 patients were enrolled. One patient was withdrawn due to unbearable skin rash after the second cycle of neoadjuvant therapy. The majority of the intention-to-treat (ITT) population was premenopausal (54.8%), had large tumors (90.3%) and metastatic nodes (58.1%) at diagnosis and hormone-receptor positive tumors (64.5%). Most participants used nab-paclitaxel (74.2%) and received mastectomy (67.7%) after neoadjuvant treatment. The tpCR and bpCR rates were 48.4% [95% confidence interval (CI): 30.8-66%] and 51.6% (95% CI: 34-69.2%), respectively. Grade ≥3 treatment-related AEs were observed in 16.1% (5/31) of the ITT population, including diarrhea (n=2, 6.5%), hand and foot numbness (n=1, 3.2%), loss of appetite (n=1, 3.2%), and skin rash (n=1, 3.2%). AE related dose reduction or pyrotinib interruption was not required. Conclusions: In female patients with HER2-positive non-metastatic BC, neoadjuvant pyrotinib monotherapy plus taxanes appears to show promising clinical benefit and controllable AEs [Chinese Clinical Trial Registry (ChiCTR2100050870)]. The long-term efficacy and safety of this regime warrant further verification.

The burgeoning importance of PIWI-interacting RNAs in cancer progression.

PIWI-interacting RNAs (piRNAs) are a class of small noncoding RNA molecules that specifically bind to piwi protein family members to exert regulatory functions in germ cells. Recent studies have found that piRNAs, as tissue-specific molecules, both play oncogenic and tumor suppressive roles in cancer progression, including cancer cell proliferation, metastasis, chemoresistance and stemness. Additionally, the atypical manifestation of piRNAs and PIWI proteins in various malignancies presents a promising strategy for the identification of novel biomarkers and therapeutic targets in the diagnosis and management of tumors. Nonetheless, the precise functions of piRNAs in cancer progression and their underlying mechanisms have yet to be fully comprehended. This review aims to examine current research on the biogenesis and functions of piRNA and its burgeoning importance in cancer progression, thereby offering novel perspectives on the potential utilization of piRNAs and piwi proteins in the management and treatment of advanced cancer.

Circular RNAs in breast cancer diagnosis, treatment and prognosis.

Breast cancer has surpassed lung cancer to become the most common malignancy worldwide. The incidence rate and mortality rate of breast cancer continue to rise, which leads to a great burden on public health. Circular RNAs (circRNAs), a new class of noncoding RNAs (ncRNAs), have been recognized as important oncogenes or suppressors in regulating cancer initiation and progression. In breast cancer, circRNAs have significant roles in tumorigenesis, recurrence and multidrug resistance that are mediated by various mechanisms. Therefore, circRNAs may serve as promising targets of therapeutic strategies for breast cancer management. This study reviews the most recent studies about the biosynthesis and characteristics of circRNAs in diagnosis, treatment and prognosis evaluation, as well as the value of circRNAs in clinical applications as biomarkers or therapeutic targets in breast cancer. Understanding the mechanisms by which circRNAs function could help transform basic research into clinical applications and facilitate the development of novel circRNA-based therapeutic strategies for breast cancer treatment.