Physical activity and idiopathic pulmonary fibrosis: A prospective cohort study in UK Biobank and Mendelian randomization analyses.

Introduction: The impact of physical activity on the incidence of idiopathic pulmonary fibrosis (IPF) remains less well studied. This study aimed to investigate the relationship between moderate-to-vigorous physical activity (MVPA) and the risk of developing IPF.

Methods: We analyzed data from a prospective cohort study within the UK Biobank involving 502,476 participants.

Effect of Vascular Senescence on the Efficacy and Safety of Warfarin: Insights from Rat Models and a Prospective Cohort Study.

Warfarin, with its narrow therapeutic range, requires the understanding of various influencing factors for personalized medication. Vascular senescence, marked by vascular stiffening and endothelial dysfunction, has an unclear effect on the efficacy and safety of warfarin. Based on previous studies, we hypothesized that vascular senescence increases the risk of bleeding during warfarin therapy.

Effects of Natural Products through Inhibiting Endoplasmic Reticulum Stress on Attenuation of Idiopathic Pulmonary Fibrosis.

With ever-increasing intensive studies of idiopathic pulmonary fibrosis (IPF), significant progresses have been made. Endoplasmic reticulum stress (ERS)/unfolded protein reaction (UPR) is associated with the development and progression of IPF, and targeting ERS/UPR may be beneficial in the treatment of IPF. Natural product is a tremendous source of new drug discovery, and accumulating studies have reported that many natural products show potential therapeutic effects for IPF via modulating one or more branches of the ERS signaling pathway.

Association of sleep traits with benign prostatic hyperplasia in middle-aged and elderly men: A prospective analysis in UK Biobank.

Aims: The association of sleep traits (insomnia, sleep duration, chronotype, daytime sleepiness, and snoring) with benign prostatic hyperplasia (BPH) is unclear. This research aimed to examine the effects of sleep traits on BPH risk.

Methods: A total of 170 241 men aged 38 to 73 years from UK Biobank were included.

Rivaroxaban Plasma Concentration and Clinical Outcomes on Older Patients with Non-valvular Atrial Fibrillation and Pulmonary Infection.

Introduction: Infection may induce thrombotic and hemorrhagic events; however, it is currently unclear whether the inflammatory response affects the coagulation function and the clinical efficacy and safety of rivaroxaban in older patients with non-valvular atrial fibrillation (NVAF).

Objective: This project aimed to assess the effectiveness and safety of the non-vitamin K antagonist oral anticoagulant rivaroxaban in older patients with NVAF complicated by infection, and to provide a basis for possible drug dose adjustment.

Methods: A total of 152 NVAF patients aged ≥ 65 years admitted to the Fifth People's Hospital of Shanghai from June 2020 to May 2022 were included in this prospective, observational study.

Multiple genetic mutations increase the risk of thrombosis associated with clopidogrel after percutaneous coronary intervention.

The effect of multiple mutations in , and genes on the effectiveness and safety of dual antiplatelet therapy after percutaneous coronary intervention remains unclear. In total, 263 Chinese Han patients were enrolled in this study. Platelet aggregation rates and thrombosis risk were used to compare clopidogrel responses and outcomes in patients with different numbers of genetic mutations.

Tanreqing injection protects against bleomycin-induced pulmonary fibrosis via inhibiting STING-mediated endoplasmic reticulum stress signaling pathway.

Ethnopharmacological Relevance: Idiopathic pulmonary fibrosis (IPF), characterized by excessive collagen deposition, is a progressive and typically fatal lung disease without effective therapeutic methods. Tanreqing injection (TRQ), a Traditional Chinese Patent Medicine, has been widely used to treat inflammatory respiratory diseases clinically.

Aim Of The Study: The present work aims to elucidate the therapeutic effects and the possible mechanism of TRQ against pulmonary fibrosis.

Traditional Chinese medicine for prevention and treatment of hepatocellular carcinoma: A focus on epithelial-mesenchymal transition.

Hepatocellular carcinoma (HCC) is one of the most prevalent malignant cancers worldwide. Epithelial-mesenchymal transition (EMT), which endows epithelial cells with mesenchymal properties, plays an important role in the early stages of metastasis. Conventional cancer therapies have promising effects, but issues remain, such as high rates of metastasis and drug resistance.

P-Rex1 Cooperates With TGFβR2 to Drive Lung Fibroblast Migration in Pulmonary Fibrosis.

Pulmonary fibrosis is a kind of interstitial lung disease with progressive pulmonary scar formation, leading to irreversible loss of lung functions. The TGF-β1/Smad signaling pathway plays a key role in fibrogenic processes. It is associated with the increased synthesis of extracellular matrix, enhanced proliferation of fibroblasts, and transformation of alveolar epithelial cells into interstitial cells.

Identification of P-Rex1 in the Regulation of Liver Cancer Cell Proliferation and Migration via HGF/c-Met/Akt Pathway.

Background: Rho-GTPases and their activators, guanine nucleotide exchange factors (GEFs), are increasingly being recognized as essential mediators of oncogenic signaling. Although it is known that P-Rex1, a member of the family of GEFs for the Rac small GTPase, contributes to the migration of cancer cells, its exact role in liver cancer and the underlying mechanisms remain unclear.

Materials And Methods: Public datasets from the Gene Expression Omnibus database (GEO) and clinical liver cancer samples were analyzed to explore the expression of P-Rex1.

Valproic acid reverses sorafenib resistance through inhibiting activated Notch/Akt signaling pathway in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the most common lethal human malignancies worldwide. Sorafenib is the first-line drug approved by the United States Food and Drug Administration for HCC. However, the acquired resistance to sorafenib reduces its beneficial effects and limits clinical use.

Valproic acid overcomes sorafenib resistance by reducing the migration of Jagged2-mediated Notch1 signaling pathway in hepatocellular carcinoma cells.

Sorafenib resistance is a classic problem related to the treatment of advanced hepatocellular carcinoma (HCC). There is a recognized need to explore new drug resistance mechanisms and develop novel strategies to overcome the acquired resistance to sorafenib. Although one study has showed that the anti-epileptic drug valproic acid (VPA) could sensitize transforming growth factor-β (TGF-β)-induced sorafenib-resistant HCC cells, it is unclear whether VPA could reverse resistance to long-term clinical treatment with sorafenib.

Interaction between Traditional Chinese Medicine and Anticoagulant/Antiplatelet Drugs.

Background: Traditional Chinese medicine (TCM) has been used for medical purposes since the ancient time and has gradually gained recognition worldwide. Nowadays, patients with thrombus presiding to anticoagulant/ antiplatelet drugs prefer taking TCM. However, an increasing number of studies on herb-drug interactions have been shown.

Tropisetron attenuates lipopolysaccharide induced neuroinflammation by inhibiting NF-κB and SP/NK1R signaling pathway.

Tropisetron, an antagonist of serotonin type 3 receptors (5-HTRs), has been investigated in colonic inflammatory process. Since substance P/neurokinin 1 receptor (SP/NK1R) signaling pathway plays a key role in several sensory neuronal inflammatory. We evaluated the anti-inflammatory activity of tropisetron in mice cerebral cortex, and discovered that it was a potential inhibitor in LPS-mediated neuron inflammation through SP/NK1R signaling pathway.

Precision Medicine: Update on Diagnosis and Therapeutic Strategies of Hepatocellular Carcinoma.

Recent advances in multiple omics technologies and the advent of massively parallel sequencing provide technical supports for the implementation of precision medicine. The precision medicine emphasizes that heterogeneous diseases can be well classified into more precise subtypes by the powerful detection methods and integration of clinical features, so that the clinicians should develop more accurate diagnosis and therapeutic strategies for the disease subtype population in an effort to maximize the efficacy and minimize the unnecessary side effects. Oncology is at the forefront of precision medicine, as malignant tumors have significant heterogeneity and are among the leading causes of death nationally and worldwide.

Combination of sorafenib and Valproic acid synergistically induces cell apoptosis and inhibits hepatocellular carcinoma growth via down-regulating Notch3 and pAkt.

Sorafenib is currently the only approved first-line targeted drug against advanced hepatocellular carcinoma (HCC). However, unsatisfactory efficacy and resistance of sorafenib raises the urgent need to develop more effective therapeutic strategies for HCC. Here, we evaluated the effects of combination of histone deacetylase inhibitor Valproic acid (VPA) and sorafenib in HCC both in vitro and in vivo.

Metabolomic approach to understand the acute and chronic hepatotoxicity of Veratrum nigrum extract in mice based on ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry.

Veratrum nigrum L. (VN) is a poisonous traditional Chinese medicine herb present since thousands of years in China. Clinical studies have shown that VN has the ability to cause hepatotoxicity, which severely limits its clinical use.

Notch Signaling Activation in Cervical Cancer Cells Induces Cell Growth Arrest with the Involvement of the Nuclear Receptor NR4A2.

Cervical cancer is a second leading cancer death in women world-wide, with most cases in less developed countries. Notch signaling is highly conserved with its involvement in many cancers. In the present study, we established stable cervical cell lines with Notch activation and inactivation and found that Notch activation played a suppressive role in cervical cancer cells.

Laboratory monitoring of rivaroxaban and assessment of its bleeding risk.

Background: The aims of this study were to investigate the effects of rivaroxaban on routine coagulation assays using our local, widely available, reagents and to study the relationship between sensitive coagulation assays and bleeding risk caused by rivaroxaban.

Methods: Prothrombin time (PT), activated partial thromboplastin time (APTT) and anti-factor Xa (FXa) chromogenic assays (Biophen DiXaI) and inhibition of FXa activity were performed in normal pooled plasma (NPP) spiked with rivaroxaban and plasma samples from patients treated with rivaroxaban.

Results: In vitro, the linear correlation coefficient of measured concentrations of rivaroxaban, by Biophen DiXaI, and spiked concentrations of rivaroxaban was 0.

The Histone Deacetylase Inhibitor Vaproic Acid Induces Cell Growth Arrest in Hepatocellular Carcinoma Cells via Suppressing Notch Signaling.

Hepatocellular carcinoma (HCC) is a type of malignant cancer. Notch signaling is aberrantly expressed in HCC tissues with more evidence showing that this signaling plays a critical role in HCCs. In the present study, we investigate the effects of the anti-convulsant drug valproic acid (VPA) in HCC cells and its involvement in modulating Notch signaling.

Valproic acid induces NET cell growth arrest and enhances tumor suppression of the receptor-targeted peptide-drug conjugate via activating somatostatin receptor type II.

Background: Human pancreatic carcinoids, a type of neuroendocrine tumors, are asymptomatic and difficult to diagnose, with the effects of traditional anti-cancer therapies being limited. The histone deacetylase (HDAC) inhibitor valproic acid (VPA) was evaluated for its effects alone and in combination with receptor-targeting peptide-drug conjugate via increasing drug internalization.

Materials And Methods: The in vitro and in vivo assays were used to evaluate the effects of VPA and somatostatin receptor-targeting camptothecin-somatostatin conjugate (CPT-SST).

Lamotrigine attenuates cerebral ischemia-induced cognitive impairment and decreases β-amyloid and phosphorylated tau in the hippocampus in rats.

Lamotrigine (LTG) has shown benefits in animal models of cerebral ischemia, but the mechanism involved was not fully studied. This study was carried out to examine the effects of LTG on cognitive dysfunction, β-amyloid1-42 accumulation, and tau protein hyperphosphorylation in the hippocampus of ischemic rats. Transient ischemic stroke was induced by middle cerebral artery occlusion.

The Applications of Targeting Anti-Cancer Agents in Cancer Therapeutics.

Anti-cancer targeting drugs appear to be a new and powerful "weapon" for cancer therapies. These targeting drugs are directed against specific molecules that are over-expressed or where certain unique factors are aberrantly expressed either in cancer cells or in diseased cell sites. Compared with traditional chemotherapeutic drugs, these targeting drugs have the advantages of high specificity, efficacy and less side effects.