Tribulus terrestris fruits are well known for their usage in pharmaceutical preparations and food supplements. The methanol extract of T. terrestris fruits showed potent inhibition against the ...papain-like protease (PLpro), an essential proteolylic enzyme for protection to pathogenic virus and bacteria. Subsequent bioactivity-guided fractionation of this extract led to six cinnamic amides (1–6) and ferulic acid (7). Compound 6 emerged as new compound possessing the very rare carbinolamide motif. These compounds (1–7) were evaluated for severe acute respiratory syndrome coronavirus (SARS-CoV) PLpro inhibitory activity to identify their potencies and kinetic behavior. Compounds (1–6) displayed significant inhibitory activity with IC50 values in the range 15.8–70.1 µM. The new cinnamic amide 6 was found to be most potent inhibitor with an IC50 of 15.8 µM. In kinetic studies, all inhibitors exhibited mixed type inhibition. Furthermore, the most active PLpro inhibitors (1–6) were proven to be present in the native fruits in high quantities by HPLC chromatogram and liquid chromatography with diode array detection and electrospray ionization mass spectrometry (LC-DAD-ESI/MS).
This study investigates and compares the reliability and reproducibility of two facial anthropometric methods about external nasal angles, 3D imaging and conventional 2D photography. 2D photograph ...images and 3D images about external nose of 30 volunteers were taken using digital camera and Morpheus 3D scanner. To evaluate intra-rater reliability, each images were taken over two different days for each subject by the same researcher. To evaluate inter-rater reliability, another researcher took each images for each subject on the first day. The reliability of each method for measuring 4 external nasal angle is obtained using intraclass correlation coefficient (ICC) and compared. Inter-rater and intra-rater reliability of both 3D imaging and 2D photography had excellent agreement in all 4 nasal angles. In the nasofacial angular parameter, Inter-rater ICC, 2D photography was significantly higher than 3D imaging. Result of intra-rater ICC also showed both 3D imaging and 2D photography had good reliability in all 4 nasal angles. Similar to those of inter-rater ICC, nasofacial angular parameter showed statistically significant differences between 3D imaging and 2D photography. In terms of reliability, both 2D and 3D showed appropriate anthropometric results and considering its own advantage, each methods can be used complementarily.
According to recent international consensus conferences, pure laparoscopic donor hepatectomy (PLDH), particularly right and left hepatectomies, is not yet considered a standard practice because ...studies remain limited. Thus, we present the outcomes of more than 500 PLDH patients, mostly receiving a right hepatectomy. To our knowledge, this is the largest study to date on PLDH. Data from all living liver donors who underwent PLDH at 5 centers in Korea until June 2018 were retrospectively analyzed. The outcomes of both donors and recipients were included. Pearson correlation analysis was used to explore the relationship between the duration of surgery and cumulative experience at each center, which reflects the learning curve. Overall, 545 PLDH cases were analyzed, including 481 right hepatectomies, 25 left hepatectomies, and 39 left lateral sectionectomies (LLS). The open conversion was necessary for 10 (1.8%) donors, and none of the donors died or experienced irreversible disability. Notably, there were 25 (4.6%) patients with major complications (higher than Clavien‐Dindo grade 3). All centers except one showed a significant decrease in surgery duration as the number of cases accumulated. Regarding recipient outcomes, there were 110 cases (20.2%) of early major complications and 177 cases (32.5%) of late major complications. This study shows the early and late postoperative outcomes of 545 donors and corresponding recipients, including 481 right hepatectomies and 25 left hepatectomies, from 5 experienced centers. Although the results are comparable to those of previously reported open donor hepatectomy series, further studies are needed to consider PLDH a new standard practice.
Introduction
Influence of early atrial fibrillation (AF) ablation, particularly cryoballoon ablation (CBA), on clinical outcome during long‐term follow‐up has not been clarified. The objective was to ...determine whether an early CBA (diagnosis‐to‐ablation of ≤6 months) strategy could affect freedom from AF recurrence after index CBA.
Methods
The study included 2605 patients from Korean CBA registry data with follow‐up >12 months after de novo CBA. The primary outcome was recurrence of atrial tachyarrhythmias (ATs) of ≥30‐s after a 3‐month blanking period.
Results
Compared to patients in early CBA group, patients in late CBA group had higher prevalence of diabetes, congestive heart failure, and chronic kidney disease, and higher mean CHA2DS2‐VAS score. During mean follow‐up of >21 months, ATs recurrence was detected in 839 (32.2%) patients. The early CBA group showed a significantly lower 2‐year recurrence rate of ATs than the late CBA group (26.1% vs. 31.7%, p = 0.043). In subgroup analysis, the early CBA group showed significantly higher 1‐year and 2‐year freedom from ATs recurrence than the late CBA group only in paroxysmal atrial fibrillation (PAF) patients in overall and propensity score matched cohorts. Multivariate analysis showed that early CBA was an independent factor for preventing ATs recurrence in PAF (hazard ratio: 0.637; 95% confidence intervals: 0.412–0.984).
Conclusion
Early CBA strategy, resulting in significantly lower ATs recurrence during 2‐year follow‐up after index CBA, might be considered as an initial rhythm control therapy in patients with paroxysmal AF.
Finasteride is commonly used for androgenetic alopecia (AGA) treatment. The aim of this study was to assess the therapeutic maintenance effect of a finasteride every other month (EOM) regimen and ...analyze clinical and laboratory differences in patients with AGA according to their treatment response. One hundred males with AGA who received finasteride 1 mg daily treatment for a year were enrolled in the study. At 1 year follow‐up, treatment responses of patients who completed the visit schedule were assessed using five scales. The patients were assigned to good or bad response groups according to their assessment. Further, they were randomly divided into two groups (daily vs. EOM) and treated with finasteride (1 mg) for 1 more year. At 2 years follow‐up, treatment efficacy was assessed. At 1‐year follow‐up, 36 patients completed the schedule, including eight and three patients in the good and bad response groups, respectively. At the 2‐year follow‐up, 23 patients completed the schedule, with nine in the daily group and 14 in the EOM group. Changes in global photographic assessment in the second year were 1.33 and 1.29 for the daily and EOM groups, respectively. The daily group showed an elevated hair density and lower concentration of dihydrotestosterone (DHT) and the DHT to testosterone ratio (DHT/T). However, the EOM group showed decreased hair density and elevated DHT and DHT/T. Following treatment response assessment after 1 year of treatment, the good response group showed early onset which was associated with maternal AGA. Analysis of serum androgen hormone magnitude of DHT reduction was much greater (54.4% vs. 44.4%). DHT/T was higher in the bad response group (1.98 vs. 2.33). We concluded that the finasteride EOM regimen showed similar maintenance effects to the daily regimen.
Recent studies have demonstrated that natural agents targeting the accumulation of reactive oxygen species (ROS) that selectively kill, leaving normal cells undamaged, can suppress prostate cancer. ...Here, we show that auriculasin, derived from Flemingia philippinensis, induces significant cell death and apoptosis via ROS generation in prostate cancer cells. Auriculasin treatment resulted in selective apoptotic cell death in LNCaP prostate cancer cells, characterized by DNA fragmentation, accumulation of sub-G1 cell population, cleavage of poly (ADP-ribose) polymerase (PARP), regulation of Bax/Bcl-2 ratio, increase of cytosolic apoptosis-inducing factor (AIF) and endonuclease G (EndoG), in addition to inhibiting tumor growth in a xenograft mouse model. Interestingly, auriculasin-induced apoptosis did not result in caspase-3, -8, and -9 activations. We found that auriculasin treatment decreased phosphorylation of AKT/mTOR/p70s6k in a dose- and time-dependent manner. Further, cellular ROS levels increased in LNCaP cells treated with auriculasin and blocking ROS accumulation with ROS scavengers resulted in inhibition of auriculasin-induced PARP cleavage, AIF increase, upregulation of Bax/Bcl-2 ratio, and decrease in AKT/mTOR phosphorylation. Taken together, these data suggest that auriculasin targets ROS-mediated caspase-independent pathways and suppresses PI3K/AKT/mTOR signaling, which leads to apoptosis and decreased tumor growth.
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•Auriculasin sensitively inhibited growth of human prostate cancer cells compared with human prostate epithelial cells.•Auriculasin induces caspase-independent apoptosis in LNCaP human prostate cancer cells.•Auriculasin-induced apoptosis in LNCaP cells was regulated by ROS generation.•Auriculasin suppressed tumor growth in xenograft athymic mouse model.
Background
Laparoscopic treatment for hepatocellular carcinoma (HCC) has increased. We retrospectively compared the perioperative and long-term oncological outcomes of laparoscopic liver resection ...(LLR) with those of open liver resection (OLR) for hepatocellular carcinoma (HCC) in well-matched patient groups using propensity score matching (PSM).
Methods
We reviewed medical records of patients with HCC who underwent liver resection between July 2007 and April 2016 at our center. In total, 2335 patients were included in this study and divided into LLR (
n
= 264) and OLR (
n
= 2071) groups. For group comparisons, 1:2 PSM was used with covariates of baseline characteristics, including tumor characteristics and surgical liver resection procedures.
Results
After PSM, there were 217 and 434 patients in the LLR and OLR groups, respectively. The LLR group had shorter hospital stays (8.9 vs. 14.8 days;
P
< 0.001) and lower postoperative morbidity (6.5% vs. 12.0%;
P
= 0.022). The 1-, 3-, and 5-year overall survival rates were 98.1%, 87.0%, and 78.6%, respectively, for the LLR group, and 98.3%, 90.8%, and 84.3%, respectively, for the OLR group (
P
= 0.570). The 1-, 3-, and 5-year disease-free survival rates were 81.0%, 62.0%, and 49.1%, respectively, for the LLR group, and 85.3%, 64.7%, and 56.2%, respectively, for the OLR group (
P
= 0.563).
Conclusions
Long-term oncological outcomes were comparable between LLR and OLR for selected patients. LLR was associated with multiple benefits, even for selected patients with cirrhosis who underwent major hepatectomy. LLR for HCC performed by an experienced surgeon could be considered a safe and feasible alternative to OLR for selected patients.
Celastrol has been reported to possess anticancer effects in various cancers; however, the precise mechanism underlying ROS-mediated mitochondria-dependent apoptotic cell death triggered by celastrol ...treatment in melanoma cells remains unknown. We showed that celastrol effectively induced apoptotic cell death and inhibited tumor growth using tissue culture and in vivo models of B16 melanoma. In addition to apoptotic cell death in B16 cells, several apoptotic events such as PARP cleavage and activation of caspase were confirmed. Pretreatment with caspase inhibitor modestly attenuated the celastrol-induced increase in PARP cleavage and sub-G1 cell population, implying that caspases play a partial role in celastrol-induced apoptosis. Moreover, ROS generation was detected following celastrol treatment. Blocking of ROS accumulation with ROS scavengers resulted in inhibition of celastrol-induced Bcl-2 family-mediated apoptosis, indicating that celastrol-induced apoptosis involves ROS generation as well as an increase in the Bax/Bcl-2 ratio leading to release of cytochrome
c
and AIF. Importantly, silencing of AIF by transfection of siAIF into cells remarkably attenuated celastrol-induced apoptotic cell death. Moreover, celastrol inhibited the activation of PI3K/AKT/mTOR signaling cascade in B16 cells. Our data reveal that celastrol inhibits growth and induces apoptosis in melanoma cells via the activation of ROS-mediated caspase-dependent and -independent pathways and the suppression of PI3K/AKT signaling.
The orifice size of the LHV trunk in LLS grafts is often too small for direct anastomosis. Several methods were developed to enlarge the graft and recipient hepatic vein orifices. This study ...described our surgical techniques to secure hepatic vein reconstruction in infant recipients and analyzed the patency outcomes. Twelve infants undergoing pediatric LDLT were selected during 2‐year study period between January 2018 and December 2019. Surgical techniques and vascular complications of graft hepatic vein outflow were analyzed. The mean recipient age was 12.5 ± 4.5 months; mean body weight was 9.4 ± 1.0 Kg; and mean graft‐recipient weight ratio was 2.8 ± 0.6%. Primary diseases were biliary atresia in six patients, metabolic diseases in two, hepatoblastoma in two, and acute liver failure in two. Eight LLS grafts were recovered through an open method, and four LLS grafts were recovered through a laparoscopic method. A small superficial LHV branch was present in five of 12 LLS grafts, which was opened to widen the graft hepatic vein orifice. Incision‐and‐patch venoplasty was performed in 10, unification venoplasty in 1 and no venoplasty in 1. All four LLS grafts recovered through a laparoscopic approach required circumferential vein patch because of very short hepatic vein stump. No patient experienced graft hepatic vein‐associated vascular complications during the follow‐up period of 19.3 ± 9.3 months. Our surgical techniques with incision‐and‐patch venoplasty for LLS grafts is beneficial to reduce the risk of hepatic vein outflow obstruction in recipients receiving LLS grafts.
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