Cannabidiol activates MAPK pathway to induce apoptosis, paraptosis, and autophagy in colorectal cancer cells.

Mitogen-activated protein kinase (MAPK) activation by natural compounds is known to be involved in the induction of apoptosis, paraptosis, and autophagy. Cannabidiol (CBD), a bioactive compound found in Cannabis sativa, is endowed with many pharmacological activities. We investigated the cytotoxic effect of CBD in a panel of colorectal cancer (CRC) cells (HT-29, SW480, HCT-116, and HCT-15). CBD induced significant cytotoxicity as evidenced by the results of MTT  assay, live-dead assay, and flow cytometric analysis. Since CBD displayed cytotoxicity against CRC cells, we examined the effect of CBD on apoptosis, paraptosis, and autophagy. CBD decreased the expression of antiapoptotic proteins and increased the Annexin-V-positive as well as TUNEL-positive cells suggesting that CBD induces apoptosis. CBD increased the expression of ATF4 (activating transcription factor 4) and CHOP (CCAAT/enhancer-binding protein homologous protein), elevated endoplasmic reticulum stress, and enhanced reactive oxygen species levels indicating that CBD also promotes paraptosis. CBD also induced the expression of Atg7, phospho-Beclin-1, and LC3 suggesting that CBD also accelerates autophagy. Since, the MAPK pathway is a common cascade that is involved in the regulation of apoptosis, paraptosis, and autophagy, we investigated the effect of CBD on the activation of JNK, p38, and ERK pathways. CBD activated all the forms of MAPK proteins and pharmacological inhibition of these proteins reverted the observed effects. Our findings implied that CBD could induce CRC cell death by activating apoptosis, paraptosis, and autophagy through the activation of the MAPK pathway.

c-MET-positive circulating tumor cells and cell-free DNA as independent prognostic factors in hormone receptor-positive/HER2-negative metastatic breast cancer.

BACKGROUND: Endocrine therapy resistance in hormone receptor-positive/HER2-negative (HR+/HER2-) breast cancer (BC) is a significant clinical challenge that poses several unmet needs in the management of the disease. This study aimed to investigate the prognostic value of c-MET-positive circulating tumor cells (cMET+ CTCs), ESR1/PIK3CA mutations, and cell-free DNA (cfDNA) concentrations in patients with hormone receptor-positive (HR+) metastatic breast cancer (mBC). METHODS: Ninety-seven patients with HR+ mBC were prospectively enrolled during standard treatment at Samsung Medical Center. CTCs were isolated from blood using GenoCTC® and EpCAM or c-MET CTC isolation kits. PIK3CA and ESR1 hotspot mutations were analyzed using droplet digital PCR. CfDNA concentrations were calculated using internal control copies from the ESR1 mutation test. Immunocytochemistry was performed to compare c-MET overexpression between primary and metastatic sites. RESULTS: The proportion of c-MET overexpression was significantly higher in metastatic sites than in primary sites (p = 0.00002). Survival analysis showed that c-MET+ CTC, cfDNA concentration, and ESR1 mutations were significantly associated with poor prognosis (p = 0.0026, 0.0021, and 0.0064, respectively) in HR+/HER2- mBC. By contrast, EpCAM-positive CTC (EpCAM+ CTC) and PIK3CA mutations were not associated with progression-free survival (PFS) in HR+/HER2- mBC. Multivariate analyses revealed that c-MET+ CTCs and cfDNA concentration were independent predictors of PFS in HR+/HER2- mBC. CONCLUSIONS: Monitoring c-MET+ CTC, rather than assessing c-MET expression in the primary BC site, could provide valuable information for predicting disease progression, as c-MET expression can change during treatment. The c-MET+ CTC count and cfDNA concentration could provide complementary information on disease progression in HR+ /HER2- mBC, highlighting the importance of integrated liquid biopsy.

Cs+ conductance in graphene membranes with Ångström-scale pores: the role of pore entrance geometry.

Recently, 2D materials, such as graphene, have been successfully implemented as artificial conduits of molecular sizes. The extreme precision with which these structures can be fabricated provides an unprecedented framework for the development of highly specific and efficient devices. In this work, we study the electrophoretic transport of Cs+ ions in a graphene membrane with effective pore heights of 3.4 Å by conducting molecular dynamics simulations. The entrance of the pore is systematically modified to investigate the effect of pore geometry on ionic conductance. Simulation results suggest a significant correlation between ionic conductance and entrance geometry, with a variation of the conductance up to 100% across the studied cases. To explain the observed correlation, two mechanisms involving an intimate relationship between ion dehydration and edge functional groups are proposed. The present study provides theoretical insights that can aid the design of graphene-based membranes with tunable ionic transport properties.

Components of the Chronic Obstructive Pulmonary Disease Assessment Test Associated with the Exacerbation of Severe Chronic Obstructive Pulmonary Disease Patients.

INTRODUCTION: The chronic obstructive pulmonary disease (COPD) Assessment Test (CAT) score is widely used for evaluating the health status of patients diagnosed with COPD. The aim of this study was to identify which components of the CAT are associated with exacerbations in severe COPD patients. METHODS: Using data from the Korean COPD Subgroup Study (KOCOSS), we identified 3,440 COPD patients, among which 1,027 patients are classified as having severe COPD based on spirometry results. The CAT scores on 8 items were evaluated and classified into respiratory and non-respiratory categories. We analyzed the association between CAT item scores and moderate-to-severe exacerbations during study enrollment and the following years. RESULTS: Patients with a history of moderate-to-severe exacerbations had higher scores on non-respiratory CAT components. Longitudinal CAT scores on all items after enrollment were higher in the moderate-to-severe exacerbation group. Additionally, the frequency of severe exacerbations was associated with specific CAT components related to limited activities, confidence leaving home, sleeplessness, and energy. CONCLUSIONS: This study revealed that the non-respiratory CAT component scores were statistically significant factors for predicting the moderate-to-severe exacerbation of severe COPD patients. Non-respiratory symptoms and functional limitations should be considered in patients with severe COPD. Interventions, such as pulmonary rehabilitation, may be needed to improve patients' overall well-being and prevent exacerbations.

Evaluation of the Clinical Efficacy and Trust in AI-Assisted Embryo Ranking: Survey-Based Prospective Study.

BACKGROUND: Current embryo assessment methods for in vitro fertilization depend on subjective morphological assessments. Recently, artificial intelligence (AI) has emerged as a promising tool for embryo assessment; however, its clinical efficacy and trustworthiness remain unproven. Simulation studies may provide additional evidence, provided that they are meticulously designed to mitigate bias and variance. OBJECTIVE: The primary objective of this study was to evaluate the benefits of an AI model for predicting clinical pregnancy through well-designed simulations. The secondary objective was to identify the characteristics of and potential bias in the subgroups of embryologists with varying degrees of experience. METHODS: This simulation study involved a questionnaire-based survey conducted on 61 embryologists with varying levels of experience from 12 in vitro fertilization clinics. The survey was conducted via Google Forms (Google Inc) in three phases: (1) phase 1, an initial assessment (December 23, 2022, to January 22, 2023); (2) phase 2, a validation assessment (March 6, 2023, to April 5, 2023); and (3) phase 3 an AI-guided assessment (March 6, 2023, to April 5, 2023). Inter- and intraobserver assessments and the accuracy of embryo selection from 360 day-5 embryos before and after AI guidance were analyzed for all embryologists and subgroups of senior and junior embryologists. RESULTS: With AI guidance, the interobserver agreement increased from 0.355 to 0.527 and from 0.440 to 0.524 for junior and senior embryologists, respectively, thus reaching similar levels of agreement. In a test of accurate embryo selection with 90 questions, the numbers of correct responses by the embryologists only, embryologists with AI guidance, and AI only were 34 (38%), 45 (50%), and 59 (66%), respectively. Without AI, the average score (accuracy) of the junior group was 33.516 (37%), while that of the senior group was 35.967 (40%), with P<.001 in the t test. With AI guidance, the average score (accuracy) of the junior group increased to 46.581 (52%), reaching a level similar to that of the senior embryologists of 44.833 (50%), with P=.34. Junior embryologists had a higher level of trust in the AI score. CONCLUSIONS: This study demonstrates the potential benefits of AI in selecting embryos with high chances of pregnancy, particularly for embryologists with 5 years or less of experience, possibly due to their trust in AI. Thus, using AI as an auxiliary tool in clinical practice has the potential to improve embryo assessment and increase the probability of a successful pregnancy.

Investigating the effects of Carpesii fructus extract on the liver transcriptome of olive flounder (Paralichthys olivaceus) as a potential antiparasitic agent.

Olive flounder (Paralichthys olivaceus), a popular aquaculture species, is plagued by the disease scuticociliatosis caused by Miamiensis avidus, which has a high mortality rate and is typically treated with chemicals such as formalin and hydrogen peroxide. However, Carpesii fructus extract has shown potential as a natural therapeutic agent by reducing the motility of M. avidus. However, despite its potential importance, the effect of the extract on fish metabolism remains unknown. In this study, the effect of Carpesii fructus extract and formalin on fish metabolism was analysed by whole transcriptome analysis in the liver of P. olivaceus. A total of 37,796 transcripts were generated and differential expression genes (DEGs) were identified in the liver of P. olivaceus treated with Carpesii fructus extract or formalin. In addition, functional analysis of DEGs between treatment groups was presented using Gene Ontology. These results will be crucial for the study of scuticociliatosis in various fish species, including P. olivaceus, and for the development of therapeutic agents for other diseases.

Network Effects of Brain Lesions Causing Central Poststroke Pain.

OBJECTIVE: This study was undertaken to test whether lesions causing central poststroke pain (CPSP) are associated with a specific connectivity profile, whether these connections are associated with metabolic changes, and whether this network aligns with neuromodulation targets for pain. METHODS: Two independent lesion datasets were utilized: (1) subcortical lesions from published case reports and (2) thalamic lesions with metabolic imaging using 18F- fluorodeoxyglucose positron emission tomography-computed tomography. Functional connectivity between each lesion location and the rest of the brain was assessed using a normative connectome (n = 1,000), and connections specific to CPSP were identified. Metabolic changes specific to CPSP were also identified and related to differences in lesion connectivity. Therapeutic relevance of the network was explored by testing for alignment with existing brain stimulation data and by prospectively targeting the network with repetitive transcranial magnetic stimulation (rTMS) in 7 patients with CPSP. RESULTS: Lesion locations causing CPSP showed a specific pattern of brain connectivity that was consistent across two independent lesion datasets (spatial r = 0.82, p < 0.0001). Connectivity differences were correlated with postlesion metabolism (r = -0.48, p < 0.001). The topography of this lesion-based pain network aligned with variability in pain improvement across 12 prior neuromodulation targets and across 32 patients who received rTMS to primary motor cortex (p < 0.05). Prospectively targeting this network with rTMS improved CPSP in 6 of 7 patients. INTERPRETATION: Lesions causing pain are connected to a specific brain network that shows metabolic abnormalities and promise as a neuromodulation target. ANN NEUROL 2022;92:834-845.

Feasibility of UTE-MRI-based radiomics model for prediction of histopathologic subtype of lung adenocarcinoma: in comparison with CT-based radiomics model.

OBJECTIVES: To assess the feasibility of the UTE-MRI radiomic model in predicting the micropapillary and/or solid (MP/S) patterns of surgically resected lung adenocarcinoma. MATERIALS AND METHODS: We prospectively enrolled 74 lesions from 71 patients who underwent UTE-MRI and CT before curative surgery for early lung adenocarcinoma. For conventional radiologic analysis, we analyzed the longest lesion diameter and lesion characteristics at both UTE-MRI and CT. Radiomic features were extracted from the volume of interest of the lesions and Rad-scores were generated using the least absolute shrinkage and selection operator with fivefold cross-validation. Six models were constructed by combining the conventional radiologic model, UTE-MRI Rad-score, and CT Rad-score. The areas under the curves (AUCs) of each model were compared using the DeLong method. Early recurrence after curative surgery was analyzed, and Kaplan-Meier survival analysis was performed. RESULTS: Twenty-four lesions were MP/S-positive, and 50 were MP/S-negative. The longitudinal size showed a small systematic difference between UTE-MRI and CT, with fair intermodality agreement of lesion characteristic (kappa = 0.535). The Rad-scores of the UTE-MRI and CT demonstrated AUCs of 0.84 and 0.841, respectively (p = 0.98). Among the six models, mixed conventional, UTE-MRI, and CT Rad-score model showed the highest diagnostic performance (AUC = 0.879). In the survival analysis, the high- and low-risk groups were successfully divided by the Rad-score in UTE-MRI (p = 0.01) and CT (p < 0.01). CONCLUSION: UTE-MRI radiomic model predicting MP/S positivity is feasible compared with the CT radiomic model. Also, it was associated with early recurrence in the survival analysis. CLINICAL RELEVANCE STATEMENT: A radiomic model utilizing UTE-MRI, which does not present a radiation hazard, was able to successfully predict the histopathologic subtype of lung adenocarcinoma, and it was associated with the patient's recurrence-free survival. KEY POINTS: • No studies have reported the ultrashort echo time (UTE)-MRI-based radiomic model for lung adenocarcinoma. • The UTE-MRI Rad-score showed comparable diagnostic performance with CT Rad-score for predicting micropapillary and/or solid histopathologic pattern. • UTE-MRI is feasible not only for conventional radiologic analysis, but also for radiomics analysis.

The effect of hepatic steatosis on liver volume determined by proton density fat fraction and deep learning-measured liver volume.

OBJECTIVES: We aimed to evaluate the effect of hepatic steatosis (HS) on liver volume and to develop a formula to estimate lean liver volume correcting the HS effect. METHODS: This retrospective study included healthy adult liver donors who underwent gadoxetic acid-enhanced MRI and proton density fat fraction (PDFF) measurement from 2015 to 2019. The degree of HS was graded at 5% PDFF intervals from grade 0 (no HS; PDFF < 5.5%). Liver volume was measured with hepatobiliary phase MRI using deep learning algorithm, and standard liver volume (SLV) was calculated as the reference lean liver volume. The association between liver volume and SLV ratio with PDFF grades was evaluated using Spearman's correlation (ρ). The effect of PDFF grades on liver volume was evaluated using the multivariable linear regression model. RESULTS: The study population included 1038 donors (mean age, 31 ± 9 years; 689 men). Mean liver volume to SLV ratio increased according to PDFF grades (ρ = 0.234, p < 0.001). The multivariable analysis indicated that SLV (ß = 1.004, p < 0.001) and PDFF grade*SLV (ß = 0.044, p < 0.001) independently affected liver volume, suggesting a 4.4% increase in liver volume per one-point increment in the PDFF grade. PDFF-adjusted lean liver volume was estimated using the formula, liver volume/[1.004 + 0.044 × PDFF grade]. The mean estimated lean liver volume to SLV ratio approximated to one for all PDFF grades, with no significant association with PDFF grades (p = 0.851). CONCLUSION: HS increases liver volume. The formula to estimate lean liver volume may be useful to adjust for the effect of HS on liver volume. KEY POINTS: • Hepatic steatosis increases liver volume. • The presented formula to estimate lean liver volume using MRI-measured proton density fat fraction and liver volume may be useful to adjust for the effect of hepatic steatosis on measured liver volume.

Efficacy and safety of HIP1601 (dual delayed-release esomeprazole) 40 mg in erosive esophagitis compared to HGP1705 (delayed-release esomeprazole) 40 mg: a multicenter, randomized, double-blind, non-inferiority study.

BACKGROUND: Proton-pump inhibitors (PPIs) are the most effective drugs for treating acid-related disorders. However, once-daily dosing with conventional PPIs fail to fully control acid secretion over 24 h. This study aimed to compare the efficacy and safety of HIP1601 (dual delayed-release esomeprazole) and HGP1705 (delayed-release esomeprazole) in patients with erosive esophagitis (EE). METHODS: We enrolled 213 patients with EE randomized in a 1:1 ratio to receive 40 mg HIP1601 (n = 107) or HGP1705 (n = 106) once daily for 4 or 8 weeks. The primary endpoint was the EE healing rate, confirmed by endoscopy up to week 8. GERD-related symptoms and treatment-emergent adverse events were compared between both groups. RESULTS: By week 8, the estimated healing rates of EE were 97.8% and 96.8% in the HIP1601 and HGP1705 groups, respectively, with a 95% confidence interval of -4.7 to 7.2. After 4 or 8 weeks of treatment, the EE healing rate at week 4, complete resolution rate of symptoms, time to sustained resolution of symptoms, and number of rescue medications used were similar in both groups. The proportion of heartburn- and acid regurgitation-free nights by week 4 were higher in the HIP1601 group compared to the HGP1705 group, but the difference did not reach clinical significance (87.7% vs. 85.8%, P = 0.514, 87.5% vs. 85.8%, P = 0.774). The number of adverse events did not differ significantly between the two groups. CONCLUSIONS: The efficacy and safety of HIP1601 40 mg were comparable to those of HGP1705 40 mg for the treatment of EE and symptomatic improvement of GERD. TRIAL REGISTRATION: NCT04080726 ( https://classic. CLINICALTRIALS: gov/ct2/show/NCT04080726 ), registration date: 25/10/2018.

Evaluation of MIC distribution and establishment of epidemiological cut-off values for Streptococcus parauberis isolated from aquatic animals.

AIMS: Streptococcus parauberis is responsible for the development of streptococcosis in marine fish. The aim of the current study was to determine the antimicrobial susceptibility of aquatic Strep. parauberis strains, thus establishing laboratory-specific epidemiological cut-off (COWT) values to distinguish wild-type (WT) and nonwild-type (NWT) strains. METHODS AND RESULTS: Using 220 Strep. parauberis isolates obtained from diseased Paralichthys olivaceus, Platichthys stellatus, and Sebastes schlegelii over 6 years from seven different locations in Korea, we established COWT values for eight common antimicrobial agents using the standard broth microdilution method. The COWT values calculated using MIC distribution with the NRI and ECOFFinder methods were the same or within one dilution step for the eight antimicrobials tested. Nine NWT isolates with decreased susceptibility to at least two antimicrobials and one of these isolates exhibited decreased susceptibility to six antimicrobial agents were identified using COWT values based on NRI. CONCLUSIONS: Interpretive criteria for Strep. parauberis have not yet been established, and the findings of this study provide putative COWT values for eight antimicrobial agents frequently used in aquaculture in Korea.

Dermatofibroma-like dermal non-neural granular cell tumor.

Non-neural granular cell tumor (NNGCT) is a rare tumor with uncertain lineage. It presents as an asymptomatic polypoid or plaque-like lesion, especially on trunk. Because the granular cells are usually strongly reactive with S-100 stain, conventional granular cell tumors (GCTs) are regarded as those of neural or Schwann cell origin. Unlike GCTs, NNGCT is not reactive for S-100 protein and is thought to derive elsewhere, presumably from mesenchymal stem cells. A 20-year-old woman presented with a solitary, dermatofibroma-like, brownish nodule on her right arm. The lesion developed 3 months before presentation without subjective symptoms. Histopathologic examination revealed a grenz zone overlying a poorly circumscribed tumor extending through the reticular dermis. The tumor cells were large and polygonal, and they had numerous eosinophilic small granules in the cytoplasm. Immunohistochemical stains were positive for CD68, vimentin, factor XIIIa, CD10, and cyclin D1. Stains for S-100 protein, neuron-specific enolase, and CD34 were negative. Based on these findings, the lesion was diagnosed as dermal NNGCT.

Safety evaluation of curative gastrectomy for gastric cancer patients who underwent liver transplantation: a comparative study with conventional gastrectomy for gastric cancer patients.

BACKGROUND: We aimed to examine the technical and oncological safety of curative gastrectomy for gastric cancer patients who underwent liver transplantation. METHODS: In this study, we compared the surgical and oncological outcomes of two groups. The first group consisted of 32 consecutive patients who underwent curative gastrectomy for gastric cancer after liver transplantation (LT), while the other group consisted of 127 patients who underwent conventional gastrectomy (CG). In addition, a subgroup analysis was performed to evaluate the impact of the background differences and the surgical outcomes on the involvement of a specialized liver transplant surgery team. RESULTS: The mean operative time was significantly longer in the LT group (p < 0.05). Furthermore, there were more frequent cases of postoperative transfusion in the LT group compared to the CG group (p < 0.05). However, there were no significant differences in the overall complications between the groups (25.00 vs 23.62%, p = 0.874). The 5-year overall survival rates of the LT and CG groups were 76.7% and 90.1%, respectively (p < 0.05). The results of the subgroup analysis demonstrated no statistically significant difference in various early surgical outcomes, such as time to transfusion during surgery, first flatus, time to first soft diet, postoperative complications, hospital stay after surgery, and the number of harvested lymph nodes except for operation time. CONCLUSIONS: Despite one's medical history of undergoing LT, our study demonstrated that curative gastrectomy could be a surgically safe treatment for gastric cancer. However, further study should be conducted to identify the reason gastric cancer patients who underwent liver transplant surgery have lower overall survival rate.

Pediatric Deaths Associated With Coronavirus Disease 2019 (COVID-19) in Korea.

As of September 3, 2022, 5,388,338 coronavirus disease 2019 (COVID-19) cases and 46 deaths (3 in 2021 and 43 in 2022) were reported in children ≤ 18 years in Korea. Cumulative confirmed cases accounted for 67.3% of the population aged ≤ 18 years and case fatality rate was 0.85/100,000. Among 46 fatal cases, 58.7% were male and median age was 7 years. Underlying diseases were present in 47.8%; neurologic diseases (63.6%) and malignancy (13.6%) most common. Only four had history of COVID-19 immunization. COVID-19 associated deaths occurred at median 2 days from diagnosis (range: -1 to 21). Among COVID-19 deaths, 41.3% occurred before admission; 2 before hospital arrival and 17 in the emergency department. Among children whose cause was documented, myocarditis, respiratory and multiorgan failure were most common. COVID-19 associated death was seen early after diagnosis in children and public health policies to provide access to medical care for children with COVID-19 are essential during the pandemic.

High-Performance Mid-IR to Deep-UV van der Waals Photodetectors Capable of Local Spectroscopy at Room Temperature.

The ability to perform broadband optical spectroscopy with subdiffraction-limit resolution is highly sought-after for a wide range of critical applications. However, sophisticated near-field techniques are currently required to achieve this goal. We bypass this challenge by demonstrating an extremely broadband photodetector based on a two-dimensional (2D) van der Waals heterostructure that is sensitive to light across over a decade in energy from the mid-infrared (MIR) to deep-ultraviolet (DUV) at room temperature. The devices feature high detectivity (>109 cm Hz1/2 W-1) together with high bandwidth (2.1 MHz). The active area can be further miniaturized to submicron dimensions, far below the diffraction limit for the longest detectable wavelength of 4.1 µm, enabling such devices for facile measurements of local optical properties on atomic-layer-thickness samples placed in close proximity. This work can lead to the development of low-cost and high-throughput photosensors for hyperspectral imaging at the nanoscale.

Euphorbiasteroid Induces Apoptosis as Well as Autophagy through Modulating SHP-1/STAT3 Pathway in Hepatocellular Carcinoma Cells.

Euphorbiasteroid (EPBS) has gained attention for its activity against human lung cancer and sarcoma; however, its impact on hepatocellular carcinoma has not yet been elucidated. Here, we investigated the cytotoxic effect of EPBS on human hepatocellular carcinoma (HCC) cells. We found that EPBS induced both apoptosis and autophagy in HCC cells. Additionally, we observed that EPBS treatment suppressed the constitutive as well as the inducible activation of a signal transducer and activator of transcription 3 (STAT3) protein expression. Moreover, EPBS promoted the expression of SHP-1 protein and the production of reactive oxidative stress (ROS). Furthermore, the knockdown of SHP-1 by siRNA transfection reversed the effects of EPBS, which have inductive effects related to apoptosis and autophagy. Therefore, EPBS can potentially function as an anti-cancer agent by inducing apoptosis and autophagy when targeting the SHP-1/STAT3 pathway.

Discovery of Pyrimidine- and Coumarin-Linked Hybrid Molecules as Inducers of JNK Phosphorylation through ROS Generation in Breast Cancer Cells.

Human epidermal growth factor receptor 2 (HER2)-positive breast cancer exhibits early relapses, poor prognoses, and high recurrence rates. Herein, a JNK-targeting compound has been developed that may be of utility in HER2-positive mammary carcinoma. The design of a pyrimidine-and coumarin-linked structure targeting JNK was explored and the lead structure PC-12 [4-(3-((2-((4-chlorobenzyl)thio) pyrimidin-4-yl)oxy)propoxy)-6-fluoro-2H-chromen-2-one (5d)] was observed to selectively inhibit the proliferation of HER2-positive BC cells. The compound PC-12 exerted DNA damage and induced apoptosis in HER-2 positive BC cells more significantly compared to HER-2 negative BC cells. PC-12 induced PARP cleavage and down-regulated the expression of IAP-1, BCL-2, SURVIVIN, and CYCLIN D1 in BC cells. In silico and theoretical calculations showed that PC-12 could interact with JNK, and in vitro studies demonstrated that it enhanced JNK phosphorylation through ROS generation. Overall, these findings will assist the discovery of new compounds targeting JNK for use in HER2-positive BC cells.

Anti-Inflammatory Activity of 1,6,7-Trihydroxy-2-(1,1-dimethyl-2-propenyl)-3-methoxyxanthone Isolated from Cudrania tricuspidata via NF-κB, MAPK, and HO-1 Signaling Pathways in Lipopolysaccharide-Stimulated RAW 264.7 and BV2 Cells.

Neuroinflammation activated by microglia affects inflammatory pain development. This study aimed to explore the anti-inflammatory properties and mechanisms of 1,6,7-trihydroxy-2-(1,1-dimethyl-2-propenyl)-3-methoxyxanthone (THMX) from Cudrania tricuspidata in microglia activation-mediated inflammatory pain. In RAW 264.7 and BV2 cells, THMX has been shown to reduce lipopolysaccharide (LPS)-induced inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and pro-inflammatory mediators and cytokines, including nitric oxide (NO), prostaglandin (PG) E2, interleukin (IL)-6, and tumor necrosis factor alpha (TNF-α). THMX also decreased LPS-induced phosphorylation of mitogen-activated protein kinase (MAPK) and the activation of p65 nuclear factor kappa B (NF-κB). Interestingly, THMX also activated heme oxygenase (HO)-1 expression. These findings suggest that THMX is a promising biologically active compound against inflammation through preventing MAPKs and NF-ĸB and activating HO-1 signaling pathways.

Effect of chlorhexidine Mouthrinse on prevention of microbial contamination during EBUS-TBNA: a randomized controlled trial.

BACKGROUND: Although endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a minimally invasive procedure, fatal infectious complications have been reported. However, adequate preventive strategies have not been determined. We aimed to investigate the effect of chlorhexidine mouthrinse on the prevention of microbial contamination during EBUS-TBNA. METHODS: In this single-center, assessor-blinded, parallel-group randomized controlled trial, we randomly assigned adult participants undergoing EBUS-TBNA using a convex probe to gargle for 1 minute with 100 mL of 0.12% chlorhexidine gluconate before EBUS-TBNA or to receive usual care (no chlorhexidine mouthrinse). Aspiration needle wash samples were collected immediately after completion of EBUS-TBNA by instilling sterile saline into the used needle. The primary outcome was colony forming unit (CFU) counts per mL of needle wash samples in aerobic cultures. Secondary outcomes were CFU counts per mL of needle wash samples in anaerobic cultures, fever within 24 hours after EBUS-TBNA, and infectious complications within 4 weeks after EBUS-TBNA. RESULTS: From January 2021 to June 2021, 106 patients received either chlorhexidine mouthrinse (n = 51) or usual care (n = 55). The median CFU counts of needle wash samples in aerobic cultures were not significantly different in the two groups (10 CFU/mL vs 20 CFU/mL; P = 0.70). There were no significant differences between the groups regarding secondary outcomes, including median CFU counts in anaerobic cultures (P = 0.41) and fever within 24 hours after EBUS-TBNA (11.8% vs 5.6%, P = 0.31). There were no infectious complications within 4 weeks in both groups. CONCLUSIONS: Chlorhexidine mouthrinse did not reduce CFU counts in needle wash samples of EBUS-TBNA. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04718922 . Registered on 22/01/2021.

Characterization of the complete mitochondrial genome of Miamiensis avidus causing flatfish scuticociliatosis.

Miamiensis avidus is a parasitic pathogen that causes the disease scuticociliatosis in teleost fish species. It is a ciliate and a free-living marine protozoan belonging to the order Philasterida, subclass Scuticociliatida, class Oligohymenophorea, and phylum Ciliophora. The complete mt-genome of M. avidus was linear and 38,695 bp in length with 47 genes, including 40 protein-coding genes, two ribosomal RNA (rRNA) genes, and five transfer RNA (tRNA) genes. Of these, 20 genes typically belong to the clusters of orthologous groups, playing roles in energy production and conversion, translation, ribosomal structure and biogenesis, and defense mechanisms. This is the first report of sequencing and characterization of the mt-genome of M. avidus, which was observed to be linear and possessing the typical ciliate mitochondrial genome organization and phylogenetic relationships. Remarkable differences were observed between M. avidus and other ciliates in the mitochondrially encoded rRNAs, extensive gene loss in ribosomal genes and tRNAs, terminal repeat sequences, and stop codon usage. A comparative and phylogenetic analysis of M. avidus and Uronema marinum of the order Hymenostomatida, which is most closely related to the order Philasterida, signified the promise of the mitogenome data of M. avidus as a valuable genetic marker in species detection and taxonomic research. The present study has potential applications in epidemiological studies and host-parasite interaction investigations facilitating disease control.