Parasitic Characteristics of Ticks (Acari: Ixodidae) Collected from Water Deer (Hydropotes inermis argyropus) and Spatiotemporal Distribution Prediction within Host-Influenced Cultivated Areas.

Tick-borne diseases result from human-ixodid tick encounters, making it crucial to understand host-ixodid tick interactions and host-dependent distribution for epidemiology and prevention. This study examines water deer patterns and ixodid tick interactions in designated croplands of South Korea over two years, finding that the highest deer presence occurred in July and the lowest in May, during crop harvesting. Four tick species were identified, with Haemaphysalis longicornis being predominant (92.2%). Tick life stage analysis revealed peak nymphs and adults in July and larvae in October. Nymph abundance correlated positively with nearby water deer. MaxEnt biodiversity prediction results indicated wider water deer distribution in summer, reflecting their tendency to use multiple croplands. Areas with nymphs and adults aligned with predicted deer presence in summer, while larval areas aligned in autumn. Increased agroforestry expanded water deer habitats, enhancing tick dispersion. Prevention involved minimizing human-deer encounters by strategic land use in tick-prone areas. This comprehensive study provides insights into preventing severe fever with thrombocytopenia syndrome in agricultural workers, emphasizing the need for targeted interventions based on host behavior and tick life stages in different seasons.

Predicting peritoneal recurrence after radical gastrectomy for gastric cancer: Validation of a prediction model (PERI-Gastric 1 and PERI-Gastric 2) on a Korean database.

BACKGROUND: Peritoneal recurrence is a significant cause of treatment failure after radical gastrectomy for gastric cancer. The prediction of metachronous peritoneal recurrence would have a significantly impact risk stratification and tailored treatment planning. This study aimed to externally validate the previously established PERI-Gastric 1 and 2 models to assess their generalizability in an independent population. METHODS: Retrospective external validation was conducted on a cohort of 8564 patients who underwent elective gastrectomy for stage Ib-IIIc gastric cancer between 1998 and 2018 at the Yonsei Cancer Center. Discrimination was tested using the area under the receiver operating characteristic curves (AUROC). Accuracy was tested by plotting observations against the predicted risk of peritoneal recurrence and analyzing the resulting calibration plots. Clinical usefulness was tested with a decision curve analysis. RESULTS: In the validation cohort, PERI-Gastric 1 and PERI-Gastric 2 exhibited an AUROC of 0.766 (95 % C.I. 0.752-0.778) and 0.767 (95 % C.I. 0.755-0.780), a calibration-in-the-large of 0.935 and 0.700, a calibration belt with a 95 % C.I. over the bisector in the risk range of 24%-33 % and 35%-47 %. The decision curve analysis revealed a positive net benefit in the risk range of 10%-42 % and 15%-45 %, respectively. CONCLUSIONS: This study presents the external validation of the PERI-Gastric 1 and 2 scores in an Eastern population. The models demonstrated fair discrimination and satisfactory calibration for predicting the risk of peritoneal recurrence after radical gastrectomy, even in Eastern patients. PERI-Gastric 1 and 2 scores could also be applied to predict the risk of metachronous peritoneal recurrence in Eastern populations.

Superior lymph node harvest by fluorescent lymphography during minimally invasive gastrectomy for gastric cancer patients with high body mass index.

BACKGROUND: Fluorescent lymphography (FL) using indocyanine green (ICG) allows for the visualization of all draining lymph nodes (LNs), thereby increasing LN retrieval. However, no studies have assessed the efficacy of FL in high body mass index (BMI) gastric cancer patients, even as LN yield decreases with increasing BMI in gastrectomy. This study aimed to investigate the influence of FL on LN retrieval in high BMI gastric cancer patients. METHODS: Gastric cancer patients who underwent laparoscopic or robotic gastrectomies from 2013 to 2021 were included. Patients were classified into two groups, with FL (FL group) or without FL (non-FL group). The effect of FL on LN retrieval was assessed by BMI. Inverse probability of treatment weighting (IPTW) was used to ensure comparability between groups. RESULTS: Retrieved LN number decreased as BMI increased regardless of FL application (P < 0.001). According to the IPTW analysis, the mean retrieved LN number was significantly higher in the FL group (48.4 ± 18.5) than in the non-FL group (39.8 ± 16.3, P < 0.001), irrespective of BMI. The FL group exhibited a significantly higher proportion of patients with 16 or more LNs (99.5%) than the non-FL group (98.1%, P < 0.001). The FL group also had a significantly higher proportion of patients with 30 or more LNs (86.6%) than the non-FL group (72.2%, P < 0.001). In both the normal and high-BMI patients, the FL group had a significantly larger percentage of patients with a higher nodal classification than the non-FL group. CONCLUSION: FL resulted in more LN retrieval, even in high BMI patients. FL ensures accurate staging by maintaining the appropriate retrieved LN number in high BMI gastric cancer patients.

Somatic Mutational Analysis in Endoscopic Ultrasound-Guided Biopsy of Pancreatic Adenocarcinoma: Assessing Yield and Impact.

INTRODUCTION: We sought to determine the yield of somatic mutational analysis from endoscopic ultrasound (EUS)-guided biopsies of pancreatic adenocarcinoma compared with that of surgical resection and to assess the impact of these results on oncologic treatment. METHODS: We determined the yield of EUS sampling and surgical resection. We evaluated the potential impact of mutational analysis by identifying actionable mutations and its direct impact by reviewing actual treatment decisions. RESULTS: Yield of EUS sampling was 89.5%, comparable with the 95.8% yield of surgical resection. More than a quarter in the EUS cohort carried actionable mutations, and of these, more than 1 in 6 had treatment impacted by mutational analysis. DISCUSSION: EUS sampling is nearly always adequate for somatic testing and may have substantial potential and real impact on treatment decisions.

Potential Tick Defense Associated with Skin and Hair Characteristics in Korean Water Deer (Hydropotes inermis argyropus).

The Korean water deer (WD), a predominant wildlife species in South Korea, is listed as vulnerable by the IUCN Red List. Despite belonging to the same family, Cervidae, WD show significantly fewer adult ixodid tick infestations compared to roe deer (RD). Ticks, which cannot fly, engage in questing behavior in natural environments to latch onto hosts. They detect signals like body temperature and host skin chemicals to navigate through the hair coat to the preferred epidermis. In light of this, we performed an extensive comparative study of the skin tissue and hair characteristics of both deer species, focusing on elements contributing to the reduced tick bite incidence in WD. Remarkably, WD exhibited more prominent blood vessels, sebaceous glands, and sweat glands, which are crucial for skin barrier functions (p < 0.005). Moreover, WD had irregular scale patterns on their hair cuticles and possessed hair that was significantly stiffer and 2.83 times thicker than that of RD (p < 0.001). These characteristics potentially impede ticks from reaching the epidermis hair in WD and RD in the context of tick bite prevention. Further investigations in this area could enhance our understanding of tick-host dynamics and contribute to developing preventive measures against tick-borne diseases in other deer species.

Identifying the best candidates for reduced port gastrectomy.

BACKGROUND: Previous studies have focused on the non-inferiority of RPG compared with conventional port gastrectomy (CPG); however, we assumed that some candidates might derive more significant benefit from RPG over CPG. METHODS: We retrospectively analyzed the clinicopathological and perioperative parameters of 1442 patients with gastric cancer treated by gastrectomy between 2009 and 2022. The C-reactive protein level on postoperative day 3 (CRPD3) was used as a surrogate parameter for surgical trauma. Patients were grouped according to the extent of gastrectomy [subtotal gastrectomy (STG) or total gastrectomy (TG)] and lymph node dissection (D1+ or D2). The degree of surgical trauma, bowel recovery, and hospital stay between RPG and CPG was compared among those patient groups. RESULTS: Of 1442 patients, 889, 354, 129, and 70 were grouped as STGD1+, STGD2, TGD1+, and TGD2, respectively. Compared with CPG, RPG significantly decreased CRPD3 only among patients in the STGD1+ group (CPG: n = 653, 84.49 mg/L, 95% CI 80.53-88.45 vs. RPG: n = 236, 70.01 mg/L, 95% CI 63.92-76.09, P < 0.001). In addition, the RPG method significantly shortens bowel recovery and hospital stay in the STGD1+ (P < 0.001 and P < 0.001), STGD2 (P < 0.001 and P < 0.001), and TGD1+ (P = 0.026 and P = 0.007), respectively. No difference was observed in the TGD2 group (P = 0.313 and P = 0.740). CONCLUSIONS: The best candidates for RPG are patients who undergo STGD1+, followed by STGD2 and TG D1+, considering the reduction in CRPD3, bowel recovery, and hospital stay.

Safety and feasibility of reduced-port robotic distal gastrectomy for gastric cancer: a phase I/II clinical trial using the da Vinci Single Port(SP) robotic system.

Minimally invasive surgery reduces surgical trauma and the size and number of incisions. The da Vinci SP robotic surgical system was designed to overcome the technical demands of single-incision laparoscopic surgery. This study aimed to demonstrate the safety and feasibility of single-port (SP) robotic distal gastrectomy (SPRDG) for patients with gastric cancer using the da Vinci SP system (Intuitive Surgical Inc., Sunnyvale, CA, USA). This study was designed as a single-arm prospective phase I/II clinical trial of SPRDG (first posted date: 21/09/2021, NCT05051670; clinicaltrials.gov). SPRDG using the da Vinci SP system was performed on 19 patients with gastric cancer between December 2021 and October 2022. The primary outcome was the safety of SPRDG as measured by major postoperative complications. The secondary outcomes were operation time, bleeding amount, bowel motility recovery, and length of hospital stay. SPRDG was performed in all 19 patients without unexpected events, such as use of additional trocars or conversion to laparoscopic or open surgery. No major complications occurred postoperatively (0/19, 0.0%). The mean operation time was 218 min (range 164-286 min). The mean hospital stay duration was 3.2 days (range 2-4 days). This phase I/II clinical trial, performed by a single expert surgeon, demonstrated the safety and feasibility of SPRDG with the da Vinci SP system in selected patients with gastric cancer. SPRDG could be a reasonable alternative to conventional or reduced-port minimally invasive gastrectomy, as it has cosmetic advantages, early recovery, and safe discharge.

Fluorescence-guided Two-port Robotic Gastrectomy Versus Conventional Laparoscopic Gastrectomy: A Nonrandomized Controlled Trial.

Objective: To compare the number of retrieved lymph nodes between conventional laparoscopic gastrectomy (CLG) and robotic gastrectomy integrated with fluorescence guidance and a two-port system (integrated robotic gastrectomy, IRG). Background: The benefits of robotic surgery over laparoscopic surgery for gastric cancer have not yet been established. Using built-in features of robotic system, further benefit can be provided to the patients with effective lymphadenectomy and enhanced recovery. Methods: A nonrandomized controlled trial was performed by a single surgeon at single-center, tertiary referral hospital between January 2018 and October 2021. Overall, 140 patients scheduled to undergo minimally invasive subtotal gastrectomy for early gastric cancer were enrolled. The primary endpoint was the number of retrieved lymph nodes. Secondary endpoints were complications, hospital stay, pain score, body image, and operative cost. Results: This study analyzed 124 patients in the per-protocol group (IRG, 64; CLG, 60). The number of retrieved lymph nodes was higher in the IRG group than those in the CLG group (IRG vs CLG; 42.1 ± 17.9 vs 35.1 ± 14.6, P = 0.019). Moreover, other surgical parameters, such as hospital stay (4.1 ± 1.0 vs 5.2 ± 1.8, P < 0.001) and body image scale (better in 4 of the 10 questions), were significantly better in the IRG than in the CLG. Conclusions: Robotic surgical procedures integrated with fluorescence guidance and a reduced-port system yielded more retrieved lymph nodes. In addition, the IRG group showed better perioperative surgical outcomes, particularly regarding the length of hospital stay and postoperative body image. Trial registration: NCT03396354.

Management of a gastric pouch staple-line leak and its adverse events with multimodal endoscopic techniques including endoscopic vacuum therapy.

Video 1Management of a gastric pouch staple-line leak and its adverse events with multimodal endoscopic techniques including endoscopic vacuum therapy.

Short-term outcomes and cost-effectiveness of laparoscopic gastrectomy with articulating instruments for gastric cancer compared with the robotic approach.

To overcome the limitations of laparoscopic surgery, robotic systems have been commonly used in the era of minimally invasive surgery despite their high cost. However, the articulation of instruments can be achieved without a robotic system at lower cost using articulating laparoscopic instruments (ALIs). Between May 2021 and May 2022, perioperative outcomes following laparoscopic gastrectomy using ALIs versus robotic gastrectomy were compared. A total of 88 patients underwent laparoscopic gastrectomy using ALIs, while 96 underwent robotic gastrectomy. Baseline characteristics were similar between the groups except for a higher proportion of patients with a medical history in the ALI group (p = 0.013). Clinicopathologic and perioperative outcomes were not significantly different between the groups. However, the operation time was significantly shorter in the ALI group (p = 0.026). No deaths occurred in either group. In conclusion, laparoscopic gastrectomy using ALIs was associated with comparable perioperative surgical outcomes and a shorter operation time compared to robotic gastrectomy in this prospective cohort study.

Prognostic impact of fluorescent lymphography on gastric cancer.

BACKGROUND: Fluorescent lymphography-guided lymphadenectomy (FL) for gastric cancer is gaining popularity. However, its impact on prognosis is not known. This study aimed to assess the prognostic impact of FL in gastric cancer patients. MATERIALS AND METHODS: This study retrospectively analyzed 5678 gastric cancer patients who underwent gastrectomy from 2013 to 2017. The survival was compared between the FLFL group and the conventional lymphadenectomy (non-FL group) using 1:1 propensity score matching after exclusion. Patients in the FL group underwent gastrectomy with systematic lymphadenectomy after endoscopic peritumoral injection of indocyanine green the day before surgery. RESULTS: After propensity score matching, the FL and non-FL groups each had 1064 patients with similar demographic and clinicopathological characteristics. All matched variables had a standardized mean difference under 0.1. The FL group showed a significantly higher number of retrieved lymph nodes (56.2±20.1) than the non-FL group (46.2±18.2, P <0.001). The FL group also had more stage III patients ( P= 0.044) than the non-FL group. The FL group demonstrated higher overall survival ( P= 0.038) and relapse-free survival ( P= 0.036) in stage III compared with the non-FL group. However, no significant differences in overall and relapse-free survival were observed between the two groups for stages I ( P= 0.420 and P= 0.120, respectively) and II ( P= 0.200 and P= 0.280, respectively). CONCLUSION: FL demonstrated a higher survival in stage III gastric cancer patients by the more accurate staging resulting from larger lymph node retrieval. Thus, given its potential to improve prognostication by enhancing staging accuracy, it is recommended as an option to consider the use of FL in clinical practice.

Chylous Ascites After Gastric Cancer Surgery: Risk Factors and Treatment Results.

PURPOSE: Although chylous ascites is a frequent complication of radical gastrectomy for gastric cancer, proper diagnostic criteria and optimal treatment strategies have not been established. This study aimed to identify the clinical features of chylous ascites and evaluate the treatment outcomes. MATERIALS AND METHODS: We retrospectively analyzed the data of patients who underwent radical gastrectomy between 2013 and 2019. Diagnosis was made when milky fluid or elevated triglyceride levels (≥100 mg/dL) appeared in the drains without a preceding infection. The clinical features, risk factors, and treatment outcomes were assessed according to the initial treatment modalities for fasting and non-fasting groups. RESULTS: Among the 7,388 patients who underwent radical gastrectomy for gastric cancer, 156 (2.1%) experienced chylous ascites. The median length of hospital stay was longer in patients with chylous ascites than in those without (median [interquartile range]: 8.0 [6.0-12.0] vs. 6.0 [5.0-8.0], P<0.001). Low body mass index (adjusted odds ratio [aOR]=0.9; P<0.001), advanced gastric cancer (aOR=1.51, P=0.024), open surgery (reference: laparoscopic surgery; aOR=1.87, P=0.003), and extent of surgical resection (reference: subtotal gastrectomy, total gastrectomy, aOR=1.5, P=0.029; proximal gastrectomy, aOR=2.93, P=0.002) were associated with the occurrence of chylous ascites. The fasting group (n=12) was hospitalized for a longer period than the non-fasting group (n=144) (15.0 [12.5-19.5] vs. 8.0 [6.0-10.0], P<0.001). There was no difference in grade III complication rate (16.7% vs. 4.2%, P=0.117) or readmission rate (16.7% vs. 11.1%, P=0.632) between the groups. CONCLUSIONS: A fat-controlled diet and medication without fasting provided adequate initial treatment for chylous ascites after radical gastrectomy for gastric cancer.

Patient-specific virtual three-dimensional surgical navigation for gastric cancer surgery: A prospective study for preoperative planning and intraoperative guidance.

Introduction: Abdominal computed tomography (CT) can accurately demonstrate organs and vascular structures around the stomach, and its potential role for image guidance is becoming increasingly established. However, solely using two-dimensional CT images to identify critical anatomical structures is undeniably challenging and not surgeon-friendly. To validate the feasibility of a patient-specific 3-D surgical navigation system for preoperative planning and intraoperative guidance during robotic gastric cancer surgery. Materials and methods: A prospective single-arm open-label observational study was conducted. Thirty participants underwent robotic distal gastrectomy for gastric cancer using a virtual surgical navigation system that provides patient-specific 3-D anatomical information with a pneumoperitoneum model using preoperative CT-angiography. Turnaround time and the accuracy of detecting vascular anatomy with its variations were measured, and perioperative outcomes were compared with a control group after propensity-score matching during the same study period. Results: Among 36 registered patients, 6 were excluded from the study. Patient-specific 3-D anatomy reconstruction was successfully implemented without any problems in all 30 patients using preoperative CT. All vessels encountered during gastric cancer surgery were successfully reconstructed, and all vascular origins and variations were identical to operative findings. The operative data and short-term outcomes between the experimental and control group were comparable. The experimental group showed shorter anesthesia time (218.6 min vs. 230.3 min; P=0.299), operative time (177.1 min vs. 193.9 min; P=0.137), and console time (129.3 min vs. 147.4 min; P=0.101) than the control group, although the differences were not statistically significant. Conclusions: Patient-specific 3-D surgical navigation system for robotic gastrectomy for gastric cancer is clinically feasible and applicable with an acceptable turnaround time. This system enables patient-specific preoperative planning and intraoperative navigation by visualizing all the anatomy required for gastrectomy in 3-D models without any error. Clinical trial registration: Clinicaltrials.gov, identifier NCT05039333.

Changes in failure to rescue after gastrectomy at a large-volume center with a 16-year experience in Korea.

Failure to rescue (FTR), the mortality rate among patients with complications, is gaining attention as a hospital quality indicator. However, comprehensive investigation into FTR has rarely been conducted after radical gastrectomy for gastric cancer patients. This study aimed to assess FTR after radical gastrectomy and investigate the associations between FTR and clinicopathologic factors, operative features, and complication types. From 2006 to 2021, 16,851 gastric cancer patients who underwent gastrectomy were retrospectively analyzed. The incidence and risk factors were analyzed for complications, mortality, and FTR. Seventy-six patients had postoperative mortality among 15,984 patients after exclusion. The overall morbidity rate was 10.49% (1676/15,984 = 10.49%), and the FTR rate was 4.53% (76/1676). Risk factor analysis revealed that older age (reference: < 60; vs. 60-79, adjusted odds ratio [OR] 2.07, 95% confidence interval [CI] 1.13-3.79, P = 0.019; vs. ≥ 80, OR 3.74, 95% CI 1.57-8.91, P = 0.003), high ASA score (vs. 1 or 2, OR 2.79, 95% CI 1.59-4.91, P < 0.001), and serosa exposure in pathologic T stage (vs. T1, OR 2.74, 95% CI 1.51-4.97, P < 0.001) were associated with FTR. Moreover, patients who underwent gastrectomy during 2016-2021 were less likely to die when complications occurred than patients who received the surgery in 2006-2010 (OR 0.35, 95% CI 0.18-0.68, P = 0.002). This investigation of FTR after gastrectomy demonstrated that the risk factors for FTR were old age, high ASA score, serosa exposure, and operation period. FTR varied according to the complication types and the period, even in the same institution.

Securing Resection Margin Using Indocyanine Green Diffusion Range on Gastric Wall during NIR Fluorescence-Guided Surgery in Early Gastric Cancer Patients.

Near-infrared (NIR) fluorescence lymphography-guided minimally invasive gastrectomy using indocyanine green (ICG) is employed to visualize draining lymphatic vessels and lymph nodes. Endoscopically injected ICG spreads along the gastric wall and emits fluorescence from the serosal surface of the stomach. We aimed to assess the efficacy of ICG diffusion in securing the resection margin. We retrospectively analyzed 503 patients with early gastric cancer located in the body of the stomach who underwent fluorescence lymphography-guided gastrectomy from 2018 to 2021. One day before surgery, ICG was endoscopically injected into four points of the submucosal layer peritumorally. We measured the extent of resection and the resection line based on the ICG diffusion area from the specimen using NIR imaging. The mean area of the ICG diffusion was 82.7 × 75.3 and 86.7 × 80.2 mm2 on the mucosal and serosal sides, respectively. After subtotal gastrectomy, the length of the proximal resection margin was 38.1 ± 20.1, 33.4 ± 22.2, and 28.7 ± 17.2 mm in gastroduodenostomy, loop gastrojejunostomy, and Roux-en-Y gastrojejunostomy, respectively. The ICG diffusion area along the gastric wall secured a resection margin of >28 mm. The ICG diffusion range can be used as a simple and easy method for determining the resection margin during gastrectomy using NIR imaging.

Reprogramming of cancer-associated fibroblasts by apoptotic cancer cells inhibits lung metastasis via Notch1-WISP-1 signaling.

The interplay between apoptotic cancer cells and the tumor microenvironment modulates cancer progression and metastasis. Cancer-associated fibroblasts (CAFs) play a crucial role in promoting these events through paracrine communication. Here, we demonstrate that conditioned medium (CM) from lung CAFs exposed to apoptotic cancer cells suppresses TGF-ß1-induced migration and invasion of cancer cells and CAFs. Direct exposure of CAFs to apoptotic 344SQ cells (ApoSQ) inhibited CAF migration and invasion and the expression of CAF activation markers. Enhanced secretion of Wnt-induced signaling protein 1 (WISP-1) by CAFs exposed to ApoSQ was required for these antimigratory and anti-invasive effects. Pharmacological inhibition of Notch1 activation or siRNA-mediated Notch1 silencing prevented WISP-1 production by CAFs and reversed the antimigratory and anti-invasive effects. Enhanced expression of the Notch ligand delta-like protein 1 on the surface of ultraviolet-irradiated apoptotic lung cancer cells triggered Notch1-WISP-1 signaling. Phosphatidylserine receptor brain-specific angiogenesis inhibitor 1 (BAI1)-Rac1 signaling, which facilitated efferocytosis by CAFs, participated in crosstalk with Notch1 signaling for optimal production of WISP-1. In addition, a single injection of ApoSQ enhanced WISP-1 production, suppressed the expression of CAF activation markers in isolated Thy1+ CAFs, and inhibited lung metastasis in syngeneic immunocompetent mice via Notch1 signaling. Treatment with CM from CAFs exposed to ApoSQ suppressed tumor growth and lung metastasis, whereas treatment with WISP-1-immunodepleted CM from CAFs exposed to ApoSQ reversed the antitumorigenic and antimetastatic effects. Therefore, treatment with CM from CAFs exposed to apoptotic lung cancer cells could be therapeutically applied to suppress CAF activation, thereby preventing cancer progression and metastasis.

Fluorescent Lymphography-Guided Lymphadenectomy during Minimally Invasive Completion Total Gastrectomy for Remnant Gastric Cancer Patients.

No study has evaluated fluorescent lymphography for lymphadenectomy in remnant gastric cancer (RGC). This study aimed to assess the clinical application of fluorescent lymphography in minimally invasive completion total gastrectomy for RGC. Patients who had undergone minimally invasive completion total gastrectomy for RGC from 2013 to 2020 were retrospectively reviewed. The perioperative outcomes and long-term prognosis were compared between patients who had undergone minimally invasive completion total gastrectomy with fluorescent lymphography (the FL group) and those without fluorescent lymphography (the non-FL group). The FL group comprised 32 patients, and the non-FL group comprised 36 patients. FL visualized lymphatics in all 32 patients without complications related to the fluorescent injection. The median number [the interquartile range] of LN retrieval was significantly higher in the FL group (17 [9.3-23.5]) than in the non-FL group (12.5 [4-17.8]); p = 0.016). The sensitivity of fluorescent lymphography in detecting metastatic LN stations was 75%, and the negative predictive value was 96.9% in the FL group. The overall relapse-free survivals were comparable between the groups (p = 0.833 and p = 0.524, respectively). FL is an effective tool to perform a more thorough lymphadenectomy during minimally invasive completion total gastrectomy for RGC. Using FL in RGC surgery may improve surgical quality and proper staging.

Inhibition of STAT6 Activation by AS1517499 Inhibits Expression and Activity of PPARγ in Macrophages to Resolve Acute Inflammation in Mice.

Signal transducer and activator of transcription 6 (STAT6) promotes an anti-inflammatory process by inducing the development of M2 macrophages. We investigated whether modulating STAT6 activity in macrophages using AS1517499, the specific STAT6 inhibitor, affects the restoration of homeostasis after an inflammatory insult by regulating PPARγ expression and activity. Administration of AS1517499 suppressed the enhanced STAT6 phosphorylation and nuclear translocation observed in peritoneal macrophages after zymosan injection. In addition, AS1517499 delayed resolution of acute inflammation as evidenced by enhanced secretion of pro-inflammatory cytokines, reduced secretion of anti-inflammatory cytokines in PLF and supernatants from peritoneal macrophages, and exaggerated neutrophil numbers and total protein levels in PLF. We demonstrate temporal increases in annexin A1 (AnxA1) protein and mRNA levels in peritoneal lavage fluid (PLF), peritoneal macrophages, and spleen in a murine model of zymosan-induced acute peritonitis. In vitro priming of mouse bone marrow-derived macrophages (BMDM) and peritoneal macrophages with AnxA1 induced STAT6 activation with enhanced PPARγ expression and activity. Using AS1517499, we demonstrate that inhibition of STAT6 activation delayed recovery of PPARγ expression and activity, as well as impaired efferocytosis. Taken together, these results suggest that activation of the STAT6 signaling pathway mediates PPARγ expression and activation in macrophages to resolve acute inflammation.

Label-free proteomics approach reveals candidate proteins in rice (Oryza sativa L.) important for ACC deaminase producing bacteria-mediated tolerance against salt stress.

The omics-based studies are important for identifying characteristic proteins in plants to elucidate the mechanism of ACC deaminase producing bacteria-mediated salt tolerance. This study evaluates the changes in the proteome of rice inoculated with ACC deaminase producing bacteria under salt-stress conditions. Salt stress resulted in a significant decrease in photosynthetic pigments, whereas inoculation of Methylobacterium oryzae CBMB20 had significantly increased pigment contents under normal and salt-stress conditions. A total of 76, 51 and 33 differentially abundant proteins (DAPs) were identified in non-inoculated salt-stressed plants, bacteria-inoculated plants under normal and salt stress conditions respectively. The abundances of proteins responsible for ethylene emission and programmed cell death were increased, and that of photosynthesis-related proteins were decreased in non-inoculated plants under salt stress. However, bacteria-inoculated plants had shown higher abundance of antioxidant proteins, RuBisCo and ribosomal proteins that are important for enhancing stress tolerance and improving plant physiological traits. Collectively, salt stress might affect plant physiological traits by impairing photosynthetic machinery and accelerating apoptosis leading to a decline in biomass. However, inoculation of plants with bacteria can assist in enhancing photosynthetic activity, antioxidant activities and ethylene regulation related proteins for attenuating salt-induced apoptosis and sustaining growth and development.

2-O-Methylhonokiol Suppresses HCV Replication via TRAF6-Mediated NF-kB Activation.

Hepatitis C virus (HCV) is associated with various liver diseases. Chronic HCV infection is characterized by an abnormal host immune response. Therefore, it is speculated that to suppress HCV, a well-regulated host immune response is necessary. 2-O-methylhonokiol was identified by the screening of anti-HCV compounds using Renilla luciferase assay in Huh 7.5/Con 1 genotype 1b replicon cells. Here, we investigated the mechanism by which 2-O-methylhonokiol treatment inhibits HCV replication using real-time PCR. Our data shows that treatment with 2-O-methylhonokiol activated innate immune responses via nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) pathway. Additionally, the immunoprecipitation result shows that treatment with 2-O-methylhonokiol augmented tumor necrosis factor receptor (TNFR)-associated factor 6 (TRAF6) by preventing p62 from binding to TRAF6, resulting in reduced autophagy caused by HCV. Finally, we reproduced our data with the conditioned media from 2-O-methylhonokiol-treated cells. These findings strongly suggest that 2-O-methylhonokiol enhances the host immune response and suppresses HCV replication via TRAF6-mediated NF-kB activation.