Retaining or improving periodontal ligament (PDL) function is crucial for restoring periodontal defects. The aim of this study was to evaluate the physiological effects of low-power laser irradiation (LPLI) on the proliferation and osteogenic differentiation of human PDL (hPDL) cells. Cultured hPDL cells were irradiated (660 nm) daily with doses of 0, 1, 2 or 4 J⋅cm(-2). Cell proliferation was evaluated by the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay, and the effect of LPLI on osteogenic differentiation was assessed by Alizarin Red S staining and alkaline phosphatase (ALP) activity. Additionally, osteogenic marker gene expression was confirmed by real-time reverse transcription-polymerase chain reaction (RT-PCR). Our data showed that LPLI at a dose of 2 J⋅cm(-2) significantly promoted hPDL cell proliferation at days 3 and 5. In addition, LPLI at energy doses of 2 and 4 J⋅cm(-2) showed potential osteogenic capacity, as it stimulated ALP activity, calcium deposition, and osteogenic gene expression. We also showed that cyclic adenosine monophosphate (cAMP) is a critical regulator of the LPLI-mediated effects on hPDL cells. This study shows that LPLI can promote the proliferation and osteogenic differentiation of hPDL cells. These results suggest the potential use of LPLI in clinical applications for periodontal tissue regeneration.
Adenine ; analogs & derivatives ; pharmacology ; Adenylyl Cyclase Inhibitors ; Alkaline Phosphatase ; analysis ; genetics ; radiation effects ; Anthraquinones ; Bone Morphogenetic Protein 2 ; genetics ; Calcium ; metabolism ; radiation effects ; Cell Culture Techniques ; Cell Differentiation ; radiation effects ; Cell Line ; Cell Proliferation ; radiation effects ; Coloring Agents ; Core Binding Factor Alpha 1 Subunit ; genetics ; Cyclic AMP ; antagonists & inhibitors ; radiation effects ; Gene Expression ; radiation effects ; Humans ; L-Lactate Dehydrogenase ; analysis ; Lasers, Semiconductor ; Low-Level Light Therapy ; instrumentation ; Osteocalcin ; genetics ; Osteogenesis ; genetics ; radiation effects ; Periodontal Ligament ; cytology ; radiation effects ; Radiation Dosage ; Real-Time Polymerase Chain Reaction ; Reverse Transcriptase Polymerase Chain Reaction ; Tetrazolium Salts ; Thiazoles

Most important international guidelines recommend the use of CHA 2 DS 2 -VASc and HASBLED scores for stroke and bleeding risk assessments in atrial fibrillation (AF) patients, respectively. The 2020 AF guidelines of European Society of Cardiology have revised the definition of “C: congestive heart failure (HF)” component, and now patients with either HF with reduced ejection fraction or preserved ejection fraction should be assigned 1 point.Hypertrophic cardiomyopathy was also included. Besides, the revised “V: vascular diseases” component included both prior myocardial infarction and “angiographically significant coronary artery disease”. It is important to understand that the stroke and bleeding risks of AF patients were not static and should be re-assessed regularly. A high HAS-BLED score itself should not be the only reason to withhold or discontinue oral anticoagulants, but remind physicians for the corrections of modifiable bleeding risk factors and more regular follow up. In the future, the AF duration and left atrial function may play an important role for personalized evaluation of individual stroke risk while more studies are necessary.

Most important international guidelines recommend the use of CHA 2 DS 2 -VASc and HASBLED scores for stroke and bleeding risk assessments in atrial fibrillation (AF) patients, respectively. The 2020 AF guidelines of European Society of Cardiology have revised the definition of “C: congestive heart failure (HF)” component, and now patients with either HF with reduced ejection fraction or preserved ejection fraction should be assigned 1 point.Hypertrophic cardiomyopathy was also included. Besides, the revised “V: vascular diseases” component included both prior myocardial infarction and “angiographically significant coronary artery disease”. It is important to understand that the stroke and bleeding risks of AF patients were not static and should be re-assessed regularly. A high HAS-BLED score itself should not be the only reason to withhold or discontinue oral anticoagulants, but remind physicians for the corrections of modifiable bleeding risk factors and more regular follow up. In the future, the AF duration and left atrial function may play an important role for personalized evaluation of individual stroke risk while more studies are necessary.

Background: Feline mammary carcinoma (FMC) is one of the most prevalent malignancies of female cats. FMC is highly metastatic and thus leads to poor disease outcomes. Among all metastases, liver metastasis occurs in about 25% of FMC patients. However, the mechanism underlying hepatic metastasis of FMC remains largely uncharacterized. Results: Herein, we demonstrate that FMC-derived extracellular vesicles (FMC-EVs) promotes the liver metastasis of FMC by activating hepatic stellate cells (HSCs) to prime a hepatic premetastatic niche (PMN). Moreover, we provide evidence that sphingosine kinase 1 (SK1) delivered by FMC-EV was pivotal for the activation of HSC and the formation of hepatic PMN. Depletion of SK1 impaired cargo sorting in FMC-EV and the EV-potentiated HSC activation, and abol‑ ished hepatic colonization of FMC cells. Conclusions Taken together, our findings uncover a previously uncharacterized mechanism underlying liver-metas‑ tasis of FMC and provide new insights into prognosis and treatment of this feline malignancy.