Objectives: The effectiveness of combining romosozumab (ROMO) with denosumab (Dmab) remains uncertain.We compare the six-month effects of Dmab plus monthly ROMO versus Dmab plus daily teriparatide (TPTD) on bone mineral density (BMD) in treatment-naïve postmenopausal women with osteoporosis. Methods: This retrospective cohort study analyzed 26 treatment-naïve postmenopausal women with primary osteoporosis. Participants received either a monthly regimen of ROMO and Dmab (N = 14) or a daily regimen of TPTD plus Dmab (N = 12). BMD at the lumbar spine, total hip, and femoral neck was measured at baseline, 3 months, and 6 months by dual-energy X-ray absorptiometry. Serum levels of C-terminal telopeptide (CTX) and procollagen type I N-terminal propeptide (P1NP) were assessed at the same intervals. Results: Both regimens significantly improved lumbar spine BMD at 6 months (ROMO + Dmab: +9.75%; TPTD +Dmab: +7.42%). Improvements in total hip and femoral neck BMD were modest and similar between groups (~2%). Serum CTX and P1NP were significantly suppressed in both groups at 3 months, but P1NP suppression waned in the TPTD + Dmab group by 6 months. No statistically significant differences in BMD or marker changes were detected between the two regimens. Conclusions Both combination therapies effectively improve lumbar spine BMD over 6 months. The ROMO +Dmab regimen yielded numerically greater increases with fewer injections.

Tumor microenvironment contributes to poor prognosis of pancreatic adenocarcinoma (PAAD) patients. Proper regulation could improve survival. Melatonin is an endogenous hormone that delivers multiple bioactivities. Here we showed that pancreatic melatonin level is associated with patients' survival. In PAAD mice models, melatonin supplementation suppressed tumor growth, while blockade of melatonin pathway exacerbated tumor progression. This anti-tumor effect was independent of cytotoxicity but associated with tumor-associated neutrophils (TANs), and TANs depletion reversed effects of melatonin. Melatonin induced TANs infiltration and activation, therefore induced cell apoptosis of PAAD cells. Cytokine arrays revealed that melatonin had minimal impact on neutrophils but induced secretion of Cxcl2 from tumor cells. Knockdown of Cxcl2 in tumor cells abolished neutrophil migration and activation. Melatonin-induced neutrophils presented an N1-like anti-tumor phenotype, with increased neutrophil extracellular traps (NETs) causing tumor cell apoptosis through cell-to-cell contact. Proteomics analysis revealed that this reactive oxygen species (ROS)-mediated inhibition was fueled by fatty acid oxidation (FAO) in neutrophils, while FAO inhibitor abolished the anti-tumor effect. Analysis of PAAD patient specimens revealed that CXCL2 expression was associated with neutrophil infiltration. CXCL2, or TANs, combined with NET marker, can better predict patients' prognosis. Collectively, we discovered an anti-tumor mechanism of melatonin through recruiting N1-neutrophils and beneficial NET formation.

BACKGROUND: Particulate matter (PM) < 2.5 μm (PM METHODS: We obtained DNA methylation and exercise data of 496 participants (aged between 30 and 70 years) from the Taiwan Biobank (TWB) database. We also extracted PM RESULTS: DLEC1 methylation and PM CONCLUSIONS We found significant positive associations between PM
Adult ; Aged ; Air Pollutants/adverse effects* ; DNA Methylation/drug effects* ; Environmental Exposure/adverse effects* ; Exercise ; Female ; Humans ; Male ; Middle Aged ; Particulate Matter/adverse effects* ; Taiwan ; Tumor Suppressor Proteins/metabolism*

Asia ; Asian Continental Ancestry Group ; Cooperative Behavior ; Early Detection of Cancer ; Humans ; International Cooperation ; Japan ; Korea ; Liver ; Lung Neoplasms ; Mass Screening ; Oceania ; Taiwan ; Thailand ; Thyroid Neoplasms

Neural oscillation is rhythmic or repetitive neural activity in the central nervous system that is usually generated by oscillatory activity of neuronal ensembles, reflecting regular and synchronized activities within these cell populations. According to several oscillatory bands covering frequencies from approximately 0.5 Hz to >100 Hz, neural oscillations are usually classified as delta oscillation (0.5-3 Hz), theta oscillation (4-12 Hz), beta oscillation (12-30 Hz), gamma oscillation (30-100 Hz) and sharp-wave ripples (>100 Hz ripples superimposed on 0.01-3 Hz sharp waves). Neural oscillation in different frequencies can be detected in different brain regions of human and animal during perception, motion and sleep, and plays an essential role in cognition, learning and memory process. In this review, we summarize recent findings on neural oscillations in hippocampus, as well as the mechanism and function of hippocampal theta oscillation, gamma oscillation and sharp-wave ripples. This review may yield new insights into the functions of neural oscillation in general.