Background: Bone-target agents (BTAs), including denosumab (DMAb), are one of the bone metastasis treatments that should continue indefinitely. However, BTAs may be interrupted in some cases. In osteoporosis, DMAb withdrawal causes a rebound effect characterized by an increased bone turnover with spine fractures and hypercalcemia; evidence of the DMAb withdrawal effect in oncology is lacking. Methods: This study aimed to identify the DMAb withdrawal effect amongst lung cancer patients treated with DMAb for bone metastases between January 2020 and December 2021. Patients who discontinued DMAb were included. Encounter notes, radiological and laboratory findings were comprehensively reviewed. Results: Thirty patients were included with a median follow-up of 21 months (interquartile range [IQR], 10-30) after DMAb discontinuation. Bisphosphonates were administered before starting DMAb in 7 patients (23.3%) and after DMAb withdrawal in 4 cases (13.3%). Three cases of DMAb withdrawal-related hypercalcemia and 3 cases of spine fractures following DMAb cessation were identified in 5 patients (16.7%), all of them were females and the median age was 65 years old (IQR, 65-70). No statistical difference in DMAb duration or number of injections was found in patients developing DMAb withdrawal-related spine fractures or hypercalcemia compared with others (binary logistic regression, p=0.688 and p=0.938, respectively). Conclusions Patients with bony-metastatic lung cancer, especially post-menopausal women, are at risk of fractures and calcium abnormalities after DMAb discontinuation, suggesting that DMAb withdrawal effect may also be present in the oncological setting. A close follow-up and careful monitoring during and after discontinuation of DMAb is necessary.

Bioassay-guided fractionation of the methanolic extract of Artemisia iwayomogi Kitamura led to the isolation of 12 known compounds (1‒12). Notably, this study marks the first report of 3-epimeridinol (1) being isolated and structurally characterized from a natural source. Additionally, compounds 3, 4, and 7 were isolated from the Asteraceae family for the first time. The structural elucidation of the isolated compound was achieved through analysis of 1D, 2D NMR, and MS data. Upon evaluation of their inhibitory effects against lipopolysaccharideinduced nitric oxide production, compound 12 demonstrated significant inhibitory activity with greater potency than the reference compound quercetin. These results established A. iwayomogi as a promising source of antiinflammatory agents.

Bioassay-guided fractionation of the methanolic extract of Artemisia iwayomogi Kitamura led to the isolation of 12 known compounds (1‒12). Notably, this study marks the first report of 3-epimeridinol (1) being isolated and structurally characterized from a natural source. Additionally, compounds 3, 4, and 7 were isolated from the Asteraceae family for the first time. The structural elucidation of the isolated compound was achieved through analysis of 1D, 2D NMR, and MS data. Upon evaluation of their inhibitory effects against lipopolysaccharideinduced nitric oxide production, compound 12 demonstrated significant inhibitory activity with greater potency than the reference compound quercetin. These results established A. iwayomogi as a promising source of antiinflammatory agents.

Background: Bone-target agents (BTAs), including denosumab (DMAb), are one of the bone metastasis treatments that should continue indefinitely. However, BTAs may be interrupted in some cases. In osteoporosis, DMAb withdrawal causes a rebound effect characterized by an increased bone turnover with spine fractures and hypercalcemia; evidence of the DMAb withdrawal effect in oncology is lacking. Methods: This study aimed to identify the DMAb withdrawal effect amongst lung cancer patients treated with DMAb for bone metastases between January 2020 and December 2021. Patients who discontinued DMAb were included. Encounter notes, radiological and laboratory findings were comprehensively reviewed. Results: Thirty patients were included with a median follow-up of 21 months (interquartile range [IQR], 10-30) after DMAb discontinuation. Bisphosphonates were administered before starting DMAb in 7 patients (23.3%) and after DMAb withdrawal in 4 cases (13.3%). Three cases of DMAb withdrawal-related hypercalcemia and 3 cases of spine fractures following DMAb cessation were identified in 5 patients (16.7%), all of them were females and the median age was 65 years old (IQR, 65-70). No statistical difference in DMAb duration or number of injections was found in patients developing DMAb withdrawal-related spine fractures or hypercalcemia compared with others (binary logistic regression, p=0.688 and p=0.938, respectively). Conclusions Patients with bony-metastatic lung cancer, especially post-menopausal women, are at risk of fractures and calcium abnormalities after DMAb discontinuation, suggesting that DMAb withdrawal effect may also be present in the oncological setting. A close follow-up and careful monitoring during and after discontinuation of DMAb is necessary.

Background: Bone-target agents (BTAs), including denosumab (DMAb), are one of the bone metastasis treatments that should continue indefinitely. However, BTAs may be interrupted in some cases. In osteoporosis, DMAb withdrawal causes a rebound effect characterized by an increased bone turnover with spine fractures and hypercalcemia; evidence of the DMAb withdrawal effect in oncology is lacking. Methods: This study aimed to identify the DMAb withdrawal effect amongst lung cancer patients treated with DMAb for bone metastases between January 2020 and December 2021. Patients who discontinued DMAb were included. Encounter notes, radiological and laboratory findings were comprehensively reviewed. Results: Thirty patients were included with a median follow-up of 21 months (interquartile range [IQR], 10-30) after DMAb discontinuation. Bisphosphonates were administered before starting DMAb in 7 patients (23.3%) and after DMAb withdrawal in 4 cases (13.3%). Three cases of DMAb withdrawal-related hypercalcemia and 3 cases of spine fractures following DMAb cessation were identified in 5 patients (16.7%), all of them were females and the median age was 65 years old (IQR, 65-70). No statistical difference in DMAb duration or number of injections was found in patients developing DMAb withdrawal-related spine fractures or hypercalcemia compared with others (binary logistic regression, p=0.688 and p=0.938, respectively). Conclusions Patients with bony-metastatic lung cancer, especially post-menopausal women, are at risk of fractures and calcium abnormalities after DMAb discontinuation, suggesting that DMAb withdrawal effect may also be present in the oncological setting. A close follow-up and careful monitoring during and after discontinuation of DMAb is necessary.

Bioassay-guided fractionation of the methanolic extract of Artemisia iwayomogi Kitamura led to the isolation of 12 known compounds (1‒12). Notably, this study marks the first report of 3-epimeridinol (1) being isolated and structurally characterized from a natural source. Additionally, compounds 3, 4, and 7 were isolated from the Asteraceae family for the first time. The structural elucidation of the isolated compound was achieved through analysis of 1D, 2D NMR, and MS data. Upon evaluation of their inhibitory effects against lipopolysaccharideinduced nitric oxide production, compound 12 demonstrated significant inhibitory activity with greater potency than the reference compound quercetin. These results established A. iwayomogi as a promising source of antiinflammatory agents.

Bioassay-guided fractionation of the methanolic extract of Artemisia iwayomogi Kitamura led to the isolation of 12 known compounds (1‒12). Notably, this study marks the first report of 3-epimeridinol (1) being isolated and structurally characterized from a natural source. Additionally, compounds 3, 4, and 7 were isolated from the Asteraceae family for the first time. The structural elucidation of the isolated compound was achieved through analysis of 1D, 2D NMR, and MS data. Upon evaluation of their inhibitory effects against lipopolysaccharideinduced nitric oxide production, compound 12 demonstrated significant inhibitory activity with greater potency than the reference compound quercetin. These results established A. iwayomogi as a promising source of antiinflammatory agents.

Bioassay-guided fractionation of the methanolic extract of Artemisia iwayomogi Kitamura led to the isolation of 12 known compounds (1‒12). Notably, this study marks the first report of 3-epimeridinol (1) being isolated and structurally characterized from a natural source. Additionally, compounds 3, 4, and 7 were isolated from the Asteraceae family for the first time. The structural elucidation of the isolated compound was achieved through analysis of 1D, 2D NMR, and MS data. Upon evaluation of their inhibitory effects against lipopolysaccharideinduced nitric oxide production, compound 12 demonstrated significant inhibitory activity with greater potency than the reference compound quercetin. These results established A. iwayomogi as a promising source of antiinflammatory agents.

The neurophysiological mechanisms by which exercise improves cognitive function have not been fully elucidated. A comprehensive and systematic review of current domestic and international neurophysiological evidence on exercise improving cognitive function was conducted from multiple perspectives. At the molecular level, exercise promotes nerve cell regeneration and synaptogenesis and maintains cellular development and homeostasis through the modulation of a variety of neurotrophic factors, receptor activity, neuropeptides, and monoamine neurotransmitters, and by decreasing the levels of inflammatory factors and other modulators of neuroplasticity. At the cellular level, exercise enhances neural activation and control and improves brain structure through nerve regeneration, synaptogenesis, improved glial cell function and angiogenesis. At the structural level of the brain, exercise promotes cognitive function by affecting white and gray matter volumes, neural activation and brain region connectivity, as well as increasing cerebral blood flow. This review elucidates how exercise improves the internal environment at the molecular level, promotes cell regeneration and functional differentiation, and enhances the brain structure and neural efficiency. It provides a comprehensive, multi-dimensional explanation of the neurophysiological mechanisms through which exercise promotes cognitive function.
Animals ; Humans ; Brain/physiology* ; Cognition/physiology* ; Exercise/physiology* ; Nerve Regeneration/physiology* ; Neuronal Plasticity/physiology*

OBJECTIVE: To investigate the effect of TBL1XR1 mutation on cell biological characteristics of diffuse large B-cell lymphoma (DLBCL). METHODS: The TBL1XR1 overexpression vector was constructed and DNA sequencing was performed to determine the mutation status. The effect of TBL1XR1 mutation on apoptosis of DLBCL cell line was detected by flow cytometry and TUNEL fluorescence assay; CCK-8 assay was used to detect the effect of TBL1XR1 mutation on cell proliferation; Transwell assay was used to detect the effect of TBL1XR1 mutation on cell migration and invasion; Western blot was used to detect the effect of TBL1XR1 mutation on the expression level of epithelial-mesenchymal transition (EMT) related proteins. RESULTS: The TBL1XR1 overexpression plasmid was successfully constructed. The in vitro experimental results showed that TBL1XR1 mutation had no significant effect on apoptosis of DLBCL cells. Compared with the control group, TBL1XR1 mutation enhanced cell proliferation, migration and invasion of DLBCL cells. TBL1XR1 gene mutation significantly increased the expression of N-cadherin protein, while the expression of E-cadherin protein decreased. CONCLUSION TBL1XR1 mutation plays a role in promoting tumor cell proliferation, migration and invasion in DLBCL. TBL1XR1 could be considered as a potential target for DLBCL therapy in future research.
Humans ; Lymphoma, Large B-Cell, Diffuse/pathology* ; Cell Proliferation ; Mutation ; Receptors, Cytoplasmic and Nuclear/genetics* ; Apoptosis ; Cell Line, Tumor ; Epithelial-Mesenchymal Transition ; Cell Movement ; Repressor Proteins/genetics* ; Nuclear Proteins/genetics* ; Cadherins/metabolism*