Activation of strigolactone biosynthesis by the DWARF14-LIKE/KARRIKIN-INSENSITIVE2 pathway in mycorrhizal angiosperms, but not in Arabidopsis, a non-mycorrhizal plant

Strigolactones (SLs) are a class of plant hormones that regulate many aspects of plant growth and development. SLs also improve symbiosis with arbuscular mycorrhizal fungi (AMF) in the rhizosphere. Recent studies have shown that the DWARF14-LIKE (D14L)/KARRIKIN-INSENSITIVE2 (KAI2) family, paralogs of the SL receptor D14, are required for AMF colonization in several flowering plants, including rice. In this study, we found that (−)-GR5, a 2′S-configured enantiomer of a synthetic SL analog (+)-GR5, significantly activated SL biosynthesis in rice roots via D14L. This result is consistent with a recent report, showing that the D14L pathway positively regulates SL biosynthesis in rice. In fact, the SL levels tended to be lower in the roots of the d14l mutant under both inorganic nutrient-deficient and -sufficient conditions. We also show that the increase in SL levels by (−)-GR5 was observed in other mycorrhizal plant species. In contrast, the KAI2 pathway did not upregulate the SL level and the expression of SL biosynthetic genes in Arabidopsis, a non-mycorrhizal plant. We also examined whether the KAI2 pathway enhances SL biosynthesis in the liverwort Marchantia paleacea, where SL functions as a rhizosphere signaling molecule for AMF. However, the SL level and SL biosynthetic genes were not positively regulated by the KAI2 pathway. These results imply that the activation of SL biosynthesis by the D14L/KAI2 pathway has been evolutionarily acquired after the divergence of bryophytes to efficiently promote symbiosis with AMF, although we cannot exclude the possibility that liverworts have specifically lost this regulatory system

Impact of Native Coronary Artery Calcification on Lesion Outcome Following Drug-Coated Balloon Angioplasty for Treatment of In-Stent Restenosis

This study aimed to clarify whether native coronary artery（CA） calcification before index percutaneous coronary intervention（PCI） has an impact on the effectiveness of drug-coated balloon（DCB） angioplasty for the treatment of in-stent restenosis（ISR）. 100consecutive patients with 166ISR lesions underwent quantitative coronary angiography（QCA） before and after index PCI and before and after DCB angioplasty for ISR. CA calcification before index PCI was assessed by angiography and results were analyzed to reveal the predictive values for target lesion revascularization（TLR） and major adverse cardiac events（MACE）. During 1.03±1.03years of follow-up, TLR occurred in 44lesions（26.5%） and MACE in 33 patients（33%）. On multivariate analysis, CA calcification before index PCI（p=0.016）, and % diameter of stenosis（%DS）≥73%（p=0.023） and minimal lumen diameter（MLD）<0.65mm（p=0.001） before DCB angioplasty were independent predictors for TLR after DCB angioplasty. MACE was also associated with CA calcification before index PCI（p=0.01）, and %DS≥73%（p=0.001） and MLD<0.65mm（p=0.01） before DCB angioplasty, but only %DS≥73% before DCB angioplasty was an independent predictor for MACE after DCB angioplasty（p=0.039）. The combination of CA calcification before index PCI and these QCA factors before DCB angioplasty was an independent and more powerful predictor for MACE than the QCA factors alone（p<0.001）. Thereafter, the combination of CA calcification and %DS≥73% before DCB angioplasty stratified the risk of MACE after DCB angioplasty（p<0.05）. CA calcification before index PCI, as well as anatomical information at ISR, have an impact on outcome after DCB angioplasty for ISR

Nicotine promotes lymph node metastasis and cetuximab resistance in head and neck squamous cell carcinoma.

Epidermal growth factor (EGF) is overexpressed in many cancers and is associated with worse prognosis. EGF binds to its cell surface receptor (EGFR), which induces EGFR phosphorylation. Phosphorylated EGFR (p‑EGFR) is translocated into the nucleus, which increases cancer cell activity. Nicotine, which is one of the main components of tobacco, is absorbed through pulmonary alveoli and mucosal epithelia in the head and neck region by smoking and moves into the blood. Nicotine in blood binds to nicotinic acetylcholine receptor (nAChR) in the central nervous system and serves a crucial role in tobacco addiction. Although nAChR localization is thought to be limited in the nervous system, nAChR is present in a wide variety of non‑neuronal cells, including cancer cells. Recent studies suggest that nicotine contributes to the metastasis and resistance to anti‑cancer drugs of various cancer cells. However, it remains unknown whether head and neck squamous cell carcinoma (HNSCC) cells can utilize nicotine‑nAChR signaling to metastasize and acquire resistance to anti‑cancer drugs, even though the mucosal epithelia of the head and neck region are the primary sites of exposure to tobacco smoke. To the best of our knowledge, the present study is the first to demonstrate the role of nicotine in metastasis and anti‑EGFR‑therapy resistance of HNSCC. The present findings demonstrated that nicotine increased proliferation, migration, invasion, p‑EGFR nuclear translocation and protein kinase B (Akt) phosphorylation in HNSCC cells. It was also demonstrated that nicotine restored cetuximab‑inhibited proliferation, migration and invasion of HNSCC cells. Finally, an in vivo experiment revealed that nicotine increased lymph node metastasis of xenografted tumors, whereas an nAChR inhibitor suppressed lymph node metastasis and p‑EGFR nuclear localization of xenografted tumors. Taken together, these results demonstrated that nicotine induced nuclear accumulation of p‑EGFR, and activation of Akt signaling. These signaling pathways elevated the activities of HNSCC cells, causing lymph node metastasis and serving a role in cetuximab resistance

Epicardial Adipose Tissue in the Right Atrium Is Associated with Progression of Atrial Fibrillation and Recurrence after Pulmonary Vein Catheter Ablation in Patients with Atrial Fibrillation

An increase in epicardial adipose tissue（EAT）in the left atrium（LA）predicts the progression of atrial fibrillation（AF）and AF recurrence after pulmonary vein catheter ablation（CA）. We hypothesized that EAT in the right atrium（RA）is also associated with the progression of AF and post-CA AF recurrence. Using 128-slice multidetector computed tomography, EAT volume and atrial volume were measured 3-dimensionally before CA in 68 patients who had proven AF（paroxysmal AF, 42; persistent AF, 26; mean age, 65±11 years; 42.6％ female）with successful CA and 21 volunteers with sinus rhythm（age, 63±13 years; 52.3％ female）. In both atria, EAT and atrial volumes were largest in patients with persistent AF, followed, in order, by those with paroxysmal AF, and then healthy volunteers（P＜0.001）. Increased EAT and atrial volumes in both atria predicted persistent AF（P＜0.001）. Fifteen patients had AF recurrence（22.1％）during the 2-year period after CA. Increased EAT volume in both atria were independent predictors for AF recurrence, and a RA EAT volume≥6.2ml was an independent predictor, with a hazard ratio of 5.47（95％ confidence interval, 1.2-24.3; P=0.03）. The combination of EAT and atrial volume in both atria was a more powerful independent prognostic factor, with a hazard ratio of 4.8（95％ confidence interval, 1.7-3.7; P=0.003）, and a sensitivity of 60％ in 9 of 15 patients, and specificity of 81.1％ in 43 of 53 patients,（P=0.003）. RA EAT is associated with the progression of AF and post-CA AF recurrence

Significance of Coronary Artery Calcium Score in the Target Lesion Evaluated by Multi-detector Computed Tomography for Selecting Treatment of Rotational Atherectomy in Patients with Coronary Artery Disease

We investigated whether coronary artery calcium score (CAC) in the target lesion on the multidetector computed tomography angiography (CTA) predicts the addition of the Rotational atherectomy (Rota) during percutaneous coronary intervention (PCI). Lesion CAC on CTA were evaluated with quantitative coronary analysis (QCA) on coronary angiography for predicting the Rota treatment in 114 consecutive patients (165 target lesions) with first PCI (68 ± 9 years old, females: 17.6%). Rota was added in 8 patients (11 lesions). The lesion length and diameter stenosis on QCA, and lesion length and lesion CAC on CTA were the primary factors associated with the addition of Rota. Using the cut-off value based on receiver operating characteristic analysis, the sensitivity and specificity for predicting the Rota based on QCA was 72.7% in 8 of 11 lesions (vessels) with Rota and the specificity was 74% in 114 of 154 without Rota in the lesion length of ≥ 23mm (χ2=10.9, p=0.001), and 54.5% in 6 of 11 lesions with Rota and the specificity was 79.2% in 122 of 154 without Rota in the diameter stenosis of ≥ 83% (χ2=6.6, p=0.01). Those based on CTA were 90.9% in 10 of 11 lesions with Rota and 77.3% in 119 of 154 without Rota in the lesion length of ≥ 34mm (χ2=24.1, p<0.001), and 90.9% in 10 of 11 with Rota and 88.3% in 136 of 154 without Rota in the lesions with CAC ≥453 (χ2=45.7, p<0.001). Lesion CAC on CTA is most predictive of addition of Rota during PCI

Non-functioning pancreatic neuroendocrine tumor accompanied with multiple liver metastases: remorseful case and literature review.

Context Pancreatic neuroendocrine tumor (P-NET) is a rare and slow-growing tumor. Unfortunately, there is no clear consensus on the role and timing of surgery for primary tumor and liver metastases, although current reports refer to liver surgery including LT for unresectable liver metastases. Case report A thirty-nine-year-old man was diagnosed with nonfunctioning pancreatic neuroendocrine tumor (P-NET) in the pancreatic head, with multiple liver metastases. The tumor was 2.5 cm in diameter and he was asymptomatic. Small but multiple metastases were detected in the liver, and no extrahepatic metastases were observed. We initially intended to control the liver metastases before resection of the primary tumor. To begin with, transarterial chemoembolization (TACE) and transcatheter arterial infusion (TAI) were repeated. Thereafter, systemic chemotherapy and biotherapy were introduced according to follow-up assessments. Unfortunately, imaging assessment at about 10 months later revealed that liver metastases were partially enlarged, although some were successfully treated. Therefore, these therapies were switched to other regimens, and TACE/TAI, systemic chemotherapies and biotherapies were repeated. Although liver metastases seemed to be stable for a while, the primary tumor was enlarged even after therapy. At 3.5 years after initial diagnosis, the primary tumor became symptomatic (pain and jaundice). Liver metastases enlarged and massive swelling of the para-aortic lymph nodes was observed. Thereafter, palliative therapy was the main course of action. He died at 4.3 years after initial diagnosis. Conclusion Our young patient could have been a candidate for initial surgery for primary tumor and might have had a chance of subsequent liver transplantation for unresectable metastases. Surgeons still face questions in deciding the best surgical scenario in patients with P-NET with liver metastases