STAT3 Decoy Oligodeoxynucleotides Suppress Liver Inflammation and Fibrosis in Liver Cancer Cells and a DDC-Induced Liver Injury Mouse Model.

Liver damage caused by various factors results in fibrosis and inflammation, leading to cirrhosis and cancer. Fibrosis results in the accumulation of extracellular matrix components. The role of STAT proteins in mediating liver inflammation and fibrosis has been well documented; however, approved therapies targeting STAT3 inhibition against liver disease are lacking. This study investigated the anti-fibrotic and anti-inflammatory effects of STAT3 decoy oligodeoxynucleotides (ODN) in hepatocytes and liver fibrosis mouse models. STAT3 decoy ODN were delivered into cells using liposomes and hydrodynamic tail vein injection into 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC)-fed mice in which liver injury was induced. STAT3 target gene expression changes were verified using qPCR and Western blotting. Liver tissue fibrosis and bile duct proliferation were assessed in animal experiments using staining techniques, and macrophage and inflammatory cytokine distribution was verified using immunohistochemistry. STAT3 decoy ODN reduced fibrosis and inflammatory factors in liver cancer cell lines and DDC-induced liver injury mouse model. These results suggest that STAT3 decoy ODN may effectively treat liver fibrosis and must be clinically investigated.

NSrp70 is a lymphocyte-essential splicing factor that controls thymocyte development.

Alternative pre-mRNA splicing is a critical step to generate multiple transcripts, thereby dramatically enlarging the proteomic diversity. Thus, a common feature of most alternative splicing factor knockout models is lethality. However, little is known about lineage-specific alternative splicing regulators in a physiological setting. Here, we report that NSrp70 is selectively expressed in developing thymocytes, highest at the double-positive (DP) stage. Global splicing and transcriptional profiling revealed that NSrp70 regulates the cell cycle and survival of thymocytes by controlling the alternative processing of various RNA splicing factors, including the oncogenic splicing factor SRSF1. A conditional-knockout of Nsrp1 (NSrp70-cKO) using CD4Cre developed severe defects in T cell maturation to single-positive thymocytes, due to insufficient T cell receptor (TCR) signaling and uncontrolled cell growth and death. Mice displayed severe peripheral lymphopenia and could not optimally control tumor growth. This study establishes a model to address the function of lymphoid-lineage-specific alternative splicing factor NSrp70 in a thymic T cell developmental pathway.

Anti-Fibrotic Effect of Synthetic Noncoding Decoy ODNs for TFEB in an Animal Model of Chronic Kidney Disease.

Despite emerging evidence suggesting that autophagy occurs during renal interstitial fibrosis, the role of autophagy activation in fibrosis and the mechanism by which autophagy influences fibrosis remain controversial. Transcription factor EB (TFEB) is a master regulator of autophagy-related gene transcription, lysosomal biogenesis, and autophagosome formation. In this study, we examined the preventive effects of TFEB suppression on renal fibrosis. We injected synthesized TFEB decoy oligonucleotides (ODNs) into the tail veins of unilateral ureteral obstruction (UUO) mice to explore the regulation of autophagy in UUO-induced renal fibrosis. The expression of interleukin (IL)-1ß, tumor necrosis factor-α (TNF-α), and collagen was decreased by TFEB decoy ODN. Additionally, TEFB ODN administration inhibited the expression of microtubule-associated protein light chain 3 (LC3), Beclin1, and hypoxia-inducible factor-1α (HIF-1α). We confirmed that TFEB decoy ODN inhibited fibrosis and autophagy in a UUO mouse model. The TFEB decoy ODNs also showed anti-inflammatory effects. Collectively, these results suggest that TFEB may be involved in the regulation of autophagy and fibrosis and that regulating TFEB activity may be a promising therapeutic strategy against kidney diseases.

Bee Venom and Its Major Component Melittin Attenuated Cutibacterium acnes- and IGF-1-Induced Acne Vulgaris via Inactivation of Akt/mTOR/SREBP Signaling Pathway.

Acne vulgaris is the most common disease of the pilosebaceous unit. The pathogenesis of this disease is complex, involving increased sebum production and perifollicular inflammation. Understanding the factors that regulate sebum production is important in identifying novel therapeutic targets for the treatment of acne. Bee Venom (BV) and melittin have multiple effects including antibacterial, antiviral, and anti-inflammatory activities in various cell types. However, the anti-lipogenic mechanisms of BV and melittin have not been elucidated. We investigated the effects of BV and melittin in models of Insulin-like growth factor-1 (IGF-1) or Cutibacterium acnes (C. acnes)-induced lipogenic skin disease. C. acnes or IGF-1 increased the expression of sterol regulatory element-binding protein-1 (SREBP-1) and proliferator-activated receptor gamma (PPAR-γ), transcription factors that regulate numerous genes involved in lipid biosynthesis through the protein kinase B (Akt)/mammalian target of rapamycin (mTOR)/SREBP signaling pathway. In this study using a C. acnes or IGF-1 stimulated lipogenic disease model, BV and melittin inhibited the increased expression of lipogenic and pro-inflammatory factor through the blockade of the Akt/mTOR/SREBP signaling pathway. This study suggests for the first time that BV and melittin could be developed as potential natural anti-acne agents with anti-lipogenesis, anti-inflammatory, and anti-C. acnes activity.

Synthetic Non-Coding RNA for Suppressing mTOR Translation to Prevent Renal Fibrosis Related to Autophagy in UUO Mouse Model.

The global burden of chronic kidney disease is increasing, and the majority of these diseases are progressive. Special site-targeted drugs are emerging as alternatives to traditional drugs. Oligonucleotides (ODNs) have been proposed as effective therapeutic tools in specific molecular target therapies for several diseases. We designed ring-type non-coding RNAs (ncRNAs), also called mTOR ODNs to suppress mammalian target rapamycin (mTOR) translation. mTOR signaling is associated with excessive cell proliferation and fibrogenesis. In this study, we examined the effects of mTOR suppression on chronic renal injury. To explore the regulation of fibrosis and inflammation in unilateral ureteral obstruction (UUO)-induced injury, we injected synthesized ODNs via the tail vein of mice. The expression of inflammatory-related markers (interleukin-1ß, tumor necrosis factor-α), and that of fibrosis (α-smooth muscle actin, fibronectin), was decreased by synthetic ODNs. Additionally, ODN administration inhibited the expression of autophagy-related markers, microtubule-associated protein light chain 3, Beclin1, and autophagy-related gene 5-12. We confirmed that ring-type ODNs inhibited fibrosis, inflammation, and autophagy in a UUO mouse model. These results suggest that mTOR may be involved in the regulation of autophagy and fibrosis and that regulating mTOR signaling may be a therapeutic strategy against chronic renal injury.

Anti-Fibrotic Effect of Synthetic Noncoding Oligodeoxynucleotide for Inhibiting mTOR and STAT3 via the Regulation of Autophagy in an Animal Model of Renal Injury.

Renal fibrosis is a common process of various kidney diseases. Autophagy is an important cell biology process to maintain cellular homeostasis. In addition, autophagy is involved in the pathogenesis of various renal disease, including acute kidney injury, glomerular diseases, and renal fibrosis. However, the functional role of autophagy in renal fibrosis remains poorly unclear. The mammalian target of rapamycin (mTOR) plays a negative regulatory role in autophagy. Signal transducer and activator of transcription 3 (STAT3) is an important intracellular signaling that may regulate a variety of inflammatory responses. In addition, STAT3 regulates autophagy in various cell types. Thus, we synthesized the mTOR/STAT3 oligodeoxynucleotide (ODN) to regulate the autophagy. The aim of this study was to investigate the beneficial effect of mTOR/STAT3 ODN via the regulation of autophagy appearance on unilateral ureteral obstruction (UUO)-induced renal fibrosis. This study showed that UUO induced inflammation, tubular atrophy, and tubular interstitial fibrosis. However, mTOR/STAT3 ODN suppressed UUO-induced renal fibrosis and inflammation. The autophagy markers have no statistically significant relation, whereas mTOR/STAT3 ODN suppressed the apoptosis in tubular cells. These results suggest the possibility of mTOR/STAT3 ODN for preventing renal fibrosis. However, the role of mTOR/STAT3 ODN on autophagy regulation needs to be further investigated.

Ameliorating Fibrotic Phenotypes of Keloid Dermal Fibroblasts through an Epidermal Growth Factor-Mediated Extracellular Matrix Remodeling.

Keloid and hypertrophic scars are skin fibrosis-associated disorders that exhibit an uncontrollable proliferation of fibroblasts and their subsequent contribution to the excessive accumulation of extracellular matrix (ECM) in the dermis. In this study, to elucidate the underlying mechanisms, we investigated the pivotal roles of epidermal growth factor (EGF) in modulating fibrotic phenotypes of keloid and hypertrophic dermal fibroblasts. Our initial findings revealed the molecular signatures of keloid dermal fibroblasts and showed the highest degree of skin fibrosis markers, ECM remodeling, anabolic collagen-cross-linking enzymes, such as lysyl oxidase (LOX) and four LOX-like family enzymes, migration ability, and cell-matrix traction force, at cell-matrix interfaces. Furthermore, we observed significant EGF-mediated downregulation of anabolic collagen-cross-linking enzymes, resulting in amelioration of fibrotic phenotypes and a decrease in cell motility measured according to the cell-matrix traction force. These findings offer insight into the important roles of EGF-mediated cell-matrix interactions at the cell-matrix interface, as well as ECM remodeling. Furthermore, the results suggest their contribution to the reduction of fibrotic phenotypes in keloid dermal fibroblasts, which could lead to the development of therapeutic modalities to prevent or reduce scar tissue formation.

LncRNAs Act as a Link between Chronic Liver Disease and Hepatocellular Carcinoma.

Long non-coding RNAs (lncRNAs) are emerging as important contributors to the biological processes underlying the pathophysiology of various human diseases, including hepatocellular carcinoma (HCC). However, the involvement of these molecules in chronic liver diseases, such as nonalcoholic fatty liver disease (NAFLD) and viral hepatitis, has only recently been considered in scientific research. While extensive studies on the pathogenesis of the development of HCC from hepatic fibrosis have been conducted, their regulatory molecular mechanisms are still only partially understood. The underlying mechanisms related to lncRNAs leading to HCC from chronic liver diseases and cirrhosis have not yet been entirely elucidated. Therefore, elucidating the functional roles of lncRNAs in chronic liver disease and HCC can contribute to a better understanding of the molecular mechanisms, and may help in developing novel diagnostic biomarkers and therapeutic targets for HCC, as well as in preventing the progression of chronic liver disease to HCC. Here, we comprehensively review and briefly summarize some lncRNAs that participate in both hepatic fibrosis and HCC.

A comparative study of intraoral versus retromandibular approach in the management of subcondylar fracture.

BACKGROUND: The purpose of this study was to compare the outcomes and effectiveness between intraoral approach and retromandibular approach for treatment of subcondylar fracture of mandible. METHODS: Between March 2011 and October 2013, 24 patients with subcondylar fractures of the mandible were treated by a single surgeon with an intraoral approach using an angulated screwdriver (n = 14) or by another surgeon using a retromandibular approach (n = 10). The interincisal distance was measured 1 week (T0), 6 weeks (T1), 3 months (T2), and 6 months (T3) postoperatively. We also compare the average operation time and the cost of operation between the two groups. RESULTS: At 6 months postoperatively, all 24 patients achieved satisfactory ranges of temporomandibular joint movement, with an interincisal distance > 40 mm without deviation and with stable centric occlusion. The intraoral group had the median interincisal distance of 14 mm at T0, 38 mm at T1, 42.5 mm at T2, and 43 mm at T3, while the retromandibular group had that of 15, 29, 35, and 42.5 mm respectively. There was no statistically significant difference between the intraoral and the retromandibular group at T0 and T4. However, significant differences were noted T1 and T2 (p < 0.01). The differences of average operation time between the intraoral (81 min) and retromandibular group (45 min) were statistically significant (p < 0.01). The cost of an operation was 369.96 ± 8.14 (United States dollar [USD]) in intraoral group and was 345.48 ± 0.0 (USD) in retromandibular group. The differences between the two groups were statistically significant (p < 0.01). CONCLUSION: In open reduction of a subcondylar fracture of the mandible, a intraoral approach using an angulated screwdriver is superior to the retromandibular approach in terms of interincisal distance, although the operation time is longer.

Surgical Treatment of Mandible Fracture Using Unsintered Hydroxyapatite/Poly L-Lactide Composite Fixation System.

Recently, absorbable plates have been used for various types of facial fractures. However, in the case of mandibular fractures, a large amount of force is applied after fixation. Thus, a firm fixation is necessary. In particular, unfavorable fractures are more frequent in mandibular fractures. Therefore, plates should be strong enough to withstand forces at the time of surgery. The purpose of this study was to determine clinical efficacy and usefulness of unsintered hydroxyapatite (u-HA)/poly (L-lactide) (PLLA) composite system by clinical application and follow-up of fixation in patients with mandible fracture. A total of 13 patients with mandible fractures were assessed for compliance with the selection criteria. Fracture site was confirmed with radiographic findings including X-ray and facial computed tomography images. Subjects who fulfilled all criteria underwent operation using HA/PLLA composite fixation system (OSTEOTRANS; Takiron Co Ltd, Osaka, Japan). After reduction of fracture site through oral or skin incision, we placed OSTEOTRANS plates on fracture line and performed rigid fixation with OSTEOTRANS-MX screws. Follow-up was performed at 1 week, 1, 3, and 6 months after surgery. Occlusion and mouth opening were checked by physical examination and radiographic finding. We also confirmed bone approximation status, bony gap change, and bone union status. All patients finished every follow-up. They were satisfied with outcomes without complications such as malocclusion, foreign body sensation, or tenderness. This study confirms that OSTEOTRANS can be used appropriately for mandibular fractures.

Apamin inhibits hepatic fibrosis through suppression of transforming growth factor ß1-induced hepatocyte epithelial-mesenchymal transition.

Apamin is an integral part of bee venom, as a peptide component. It has long been known as a highly selective block Ca(2+)-activated K(+) (SK) channels. However, the cellular mechanism and anti-fibrotic effect of apamin in TGF-ß1-induced hepatocytes have not been explored. In the present study, we investigated the anti-fibrosis or anti-EMT mechanism by examining the effect of apamin on TGF-ß1-induced hepatocytes. AML12 cells were seeded at ∼60% confluence in complete growth medium. Twenty-four hours later, the cells were changed to serum free medium containing the indicated concentrations of apamin. After 30 min, the cells were treated with 2 ng/ml of TGF-ß1 and co-cultured for 48 h. Also, we investigated the effects of apamin on the CCl4-induced liver fibrosis animal model. Treatment of AML12 cells with 2 ng/ml of TGF-ß1 resulted in loss of E-cadherin protein at the cell-cell junctions and concomitant increased expression of vimentin. In addition, phosphorylation levels of ERK1/2, Akt, Smad2/3 and Smad4 were increased by TGF-ß1 stimulation. However, cells treated concurrently with TGF-ß1 and apamin retained high levels of localized expression of E-cadherin and showed no increase in vimentin. Specifically, treatment with 2 µg/ml of apamin almost completely blocked the phosphorylation of ERK1/2, Akt, Smad2/3 and Smad4 in AML12 cells. In addition, apamin exhibited prevention of pathological changes in the CCl4-injected animal models. These results demonstrate the potential of apamin for the prevention of EMT progression induced by TGF-ß1 in vitro and CCl4-injected in vivo.

Systemic cytotoxic chemotherapy of patients with advanced hepatocellular carcinoma in the era of sorafenib nonavailability.

GOALS: The goal of the study was to compare the efficacy and safety of sorafenib with those of systemic cytotoxic chemotherapy. BACKGROUND: Sorafenib treatment has shown to improve the survival in patients with advanced hepatocellular carcinoma (HCC) when compared with placebo. However, whether sorafenib controls advanced-stage HCC better than systemic cytotoxic chemotherapy has not been elucidated. STUDY: We retrospectively reviewed the medical records of 220 patients with measurable advanced HCC who had not received systemic treatment previously between January 2007 and April 2012. Among these patients, 78 had been treated with sorafenib. Another 14 patients who were treated with a 4-weekly regimen of adriamycin, cisplatin, and capecitabine were included as the historical control group for comparison. The median overall survival, the progression-free survival, response rates, and safety profiles were evaluated. RESULTS: Baseline characteristics were similar between the treatment groups. The median overall survival was 7.2 months [95% confidence interval (CI), 5.6-8.8] in the sorafenib group and 11.2 months (95% CI, 8.1-14.2) in the cytotoxic chemotherapy group (P=0.10). The median progression-free survival was 3.2 months (95% CI, 2.2-4.3) in the sorafenib group and 5.9 months (95% CI, 3.6-8.2) in the cytotoxic chemotherapy group (P=0.07). The deterioration of liver function and neutropenia were the most frequent serious adverse events in the sorafenib and the systemic chemotherapy group. CONCLUSIONS: Although a direct head-to-head comparison could not be done, there were some patients who showed a good response to systemic cytotoxic chemotherapy. Further assessment is necessary to study the role of chemotherapy in patients who are intolerant or intractable to sorafenib.

Synergistic effect of simvastatin plus NS398 on inhibition of proliferation and survival in hepatocellular carcinoma cell line.

BACKGROUND AND AIMS: NS398, a selective cyclooxygenase-2 inhibitor, and simvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, both exert an anticancer effect on hepatocellular carcinoma cells, but the effect of co-administration of the two drugs remains unknown. We aimed to investigate the synergistic in vitro anticancer effect of co-administration of NS398 and simvastatin and its mechanism. METHODS: The Hep3B and Huh-7 cell lines were cultured. Cells were treated with simvastatin, NS398, or a combination. 5-bromo-2'-deoxyuridine ELISA assay, flow cytometry, Western blot analyses, and immunofluorescence assay were performed. RESULTS: In both cell lines, co-administration of simvastatin and NS398 resulted in a greater effect on proliferation and apoptosis. In Hep3B cells, co-administration of the two drugs resulted in a greater decrease in procaspase 3 and Bcl-2 and an increase in cleaved caspase 9 than that noted with monotherapy. In Huh-7 cells, co-administration of the two drugs resulted in a greater decrease in procaspase 3 and cyclin D1 and an increase in cleaved caspase 9. Expression of NF-κB and Akt were also decreased to a greater extent when the two drugs were co-administered in both cell lines. Immunofluorescence assay showed suppression of the nuclear localization of NF-κB by simvastatin or NS398. The effect was greater by co-administration. CONCLUSIONS: The co-administration of NS398 and simvastatin produced greater antiproliferative and proapoptotic effects against Hep3B cells and Huh-7 cells. Inhibition of the NF-κB and Akt pathway and activation of caspase cascade, which are considered as the major mechanism of synergistic anticancer properties, were observed in both cell lines.

Temperamental and Neuropsychological Predictors for Major League Pro-Baseball Success.

BACKGROUND: Securing a professional baseball career is a formidable task, and only a unique few can overcome the obstacles necessary to become a Major League player in the Korea Baseball Organization (KBO). When achieving a spot in a KBO Major League team, a player's technical aspect may be influenced by their initial neuropsychological status. HYPOTHESIS: Personality and neurocognitive functions influence long-term pro-baseball league success. STUDY DESIGN: Cohort observational study. LEVEL OF EVIDENCE: Level 3. METHODS: From the start of each player's career, we monitored the status and course of 153 baseball players in the KBO from 2009 to 2019 who agreed to participate in this study. The Korean versions of the Temperament and Character Inventory (TCI) and the State-Trait Anxiety Inventory-Y (STAI-KY) analyzed traits and estimated state and trait anxiety levels, respectively. The Trail Making Test (TMT) (parts A and B) assessed attention shifting, and, in the Wisconsin Card Sorting Test (WCST), perseverative errors determined cognitive flexibility. Hierarchical logistic regression models were used to predict player status variables, with TCI and neurocognitive function variables as covariates. RESULTS: High novelty-seeking scores, low state anxiety, and short TMT A results reliably predict KBO Major League participation in a player's third year. Similarly, low state anxiety scores and high harm avoidance, reward dependence, and self-transcendence scores accurately predict KBO Major League participation in a player's fifth year. Lastly, short TMT A results, low perseverative error scores, and high novelty-seeking, harm avoidance, reward dependence, and self-transcendence efficiently predict KBO Major League participation in a player's seventh year. CONCLUSION: Draft ranking, personality, and neurocognitive function are associated with pro-baseball league achievement. In particular, personality and neuropsychological functions are associated with long-term success. CLINICAL RELEVANCE: Clinically, sound personality and neuropsychological functions determine KBO Major League success.

A nationwide seroepidemiology of hepatitis C virus infection in South Korea.

BACKGROUND & AIMS: The aim of this study was to reveal nationwide seroprevalence of HCV infection in South Korea by a large-scale survey. METHODS: From January to December 2009, a total of 291 314 adults underwent health check-up in 29 centres nationwide. The data concerning anti-HCV antibody and biochemical tests were obtained from all participants. Among subjects with positive anti-HCV, such data as HCV RNA, genotypes and treatment detail were additionally analysed. RESULTS: Using an estimated 2009 population of Korea, the age, sex and area-adjusted anti-HCV positive rate was 0.78%. Anti-HCV prevalence in female patients (0.83%) was higher than that in male patients (0.75%). Gradual increase in anti-HCV positivity was observed, from 0.34% in those aged 20-29 years to 2.31% in those >70 years. The age- and sex-adjusted anti-HCV prevalence varied in different areas, being higher in Busan and Jeonnam (1.53-2.07%), mid-level in Seoul and surrounding districts (0.50-0.61%) and lower in Jeju (0.23%). The comparative analysis of laboratory variables between anti-HCV (+) and anti-HCV (-) group revealed significantly higher levels of alanine aminotransferase and lower levels of serum lipids in anti-HCV (+) group. Among 1 718 anti-HCV positive subjects, serum HCV RNA was measured only in 478 people, of whom 268 (56.1%) patients had detectable HCV RNA in serum. Among 50 patients for whom assessment of response to antiviral therapy was feasible, overall sustained virological response was achieved in 84% of patients. CONCLUSION: The prevalence of HCV infection is low in South Korea. Studies to analyse risk factors are warranted to reduce HCV infection.

Treatment of lamivudine-resistant chronic hepatitis B infection: a multicenter retrospective study.

OBJECTIVES: To compare the efficacy of rescue therapies in lamivudine (LAM)-resistant chronic hepatitis B (CHB) infections including: (1) adefovir dipivoxil (ADV) monotherapy, (2) ADV plus LAM combination therapy and (3) entecavir (ETV) 1.0 mg monotherapy. MATERIALS AND METHODS: The authors designed a multicenter-retrospective study. Eight institutions participated in the study from Korea. RESULTS: A total of 343 LAM-resistant CHB patients were enrolled. The proportion of patients with undetectable serum hepatitis B virus (HBV) DNA levels at month 24 after the initiation of rescue therapy was higher in the ADV plus LAM combination therapy group (39/64, 60.9%) than in the ADV monotherapy (50/126, 39.7%) and ETV 1.0 mg monotherapy (19/48, 39.6%) groups (p = 0.014). Mean serum HBV DNA levels at 24 months were 2.07 ± 1.21 log(10) IU/ml in the ADV plus LAM combination therapy group, 2.74 ± 1.74 log(10) IU/ml in the ADV monotherapy group and 3.08 ± 1.97 log(10) IU/ml in the ETV 1.0 mg monotherapy group (p = 0.014). In multivariate analysis, a finding of undetectable serum HBV DNA level at 6 months and ADV plus LAM combination therapy (vs. ADV) was an independent factor for predicting undetectable serum HBV DNA at month 24 (odds ratio, 1.003; 95% confidence interval, 1.000-1.006; p = 0.026). CONCLUSIONS: ADV plus LAM combination therapy is more effective in reducing viral load than switching to ADV or ETV 1.0 mg in patients with LAM-resistant CHB.

Reduction process of dislocation and standby leakage current for embedded flash memory using nano-scale integration.

We determined that the use of densification, sacrificial oxidation, gate oxidation and source/drain implantation has the capability to reduce the dislocation. A dislocation-free process is proposed, and its mechanism presented in embedded flash memory. The dislocation decreased when n-type ions were implanted at a low energy level for source and drain. A dry oxidation process using only oxygen without hydrogen and oxidation for logic gates led to the formation of a sacrificial oxide on the rapid thermal oxidation (RTP) methods without densification after gap-filling as reducing dislocation processes. These methods dramatically reduced the standby leakage current.

Association between Preoperative 18-FDG PET-CT SUVmax and Next-Generation Sequencing Results in Postoperative Ovarian Malignant Tissue in Patients with Advanced Ovarian Cancer.

This study investigated the association between maximum standardized uptake values (SUVmax) on preoperative 18-FDG PET-CT and next-generation sequencing (NGS) results in post-surgical ovarian malignant tissue in patients with advanced ovarian cancer. Twenty-five patients with stage IIIC or IV ovarian cancer who underwent both preoperative 18-FDG PET-CT and postoperative NGS for ovarian malignancies were retrospectively enrolled. Two patients had no detected variants, 21 of the 23 patients with any somatic variant had at least one single nucleotide variant (SNV) or insertion/deletion (indel), 10 patients showed copy number variation (CNV), and two patients had a fusion variant. SUVmax differed according to the presence of SNVs/indels, with an SUVmax of 13.06 for patients with ≥ 1 SNV/indel and 6.28 for patients without (p = 0.003). Seventeen of 20 patients with Tier 2 variants had TP53 variants, and there was a statistically significant association between SUVmax and the presence of TP53 variants (13.21 vs. 9.35, p = 0.041). Analysis of the correlation between the sum of the Tier 1 and Tier 2 numbers and SUVmax showed a statistically significant correlation (p = 0.002; Pearson's r = 0.588). In conclusion, patients with advanced ovarian cancer with SNVs/indels on NGS, especially those with TP53 Tier 2 variants, showed a proportional association with tumor SUVmax on preoperative PET-CT.

Assessment of effectiveness in stabilization/solidification of arsenic-contaminated soil: long-term leaching test and geophysical measurement.

This study focused on evaluating the effectiveness of stabilizer/binding agents in immobilizing arsenic (As) in contaminated soil using both geochemical and geophysical monitoring methods. The effluent from the stabilizer/binding agent's application and control columns was analyzed, and the status of the columns was monitored using electrical resistivity (ER) and induced polarization (IP) methods. As stabilizers/binder, acid mine drainage sludge (AMDS) and steel slag (SS) were used, which delayed As and Ca leaching time and significantly reduced As leaching amount. Determination coefficients for As and Fe leaching exhibited elevated values (control column, R2 = 0.955; AMDS column, R2 = 0.908; and SS column, R2 = 0.833). A discernible decline in the concentration of leached Fe was accompanied by a corresponding reduction in IP. The determination coefficients correlating IP and Fe leaching remained substantial (control column, R2 = 0.768; AMDS column, R2 = 0.807; and SS column, R2 = 0.818). Such IP measurements manifest as instrumental tools in monitoring and assessing the retention capacity of applied stabilizer/binding agents in As-affected soils, thereby furnishing crucial data for the enduring surveillance of stabilization/solidification locales. This research posits a swift and continuous monitoring method for solidification/stabilization locales in situ.

Protective Effects of Carnosol on Renal Interstitial Fibrosis in a Murine Model of Unilateral Ureteral Obstruction.

Renal fibrosis is a common feature of chronic kidney disease and is a promising therapeutic target. However, there is still limited treatment for renal fibrosis, so the development of new anti-fibrotic agents is urgently needed. Accumulating evidence suggest that oxidative stress and endoplasmic reticulum (ER) stress play a critical role in renal fibrosis. Carnosol (CS) is a bioactive diterpene compound present in rosemary plants and has potent antioxidant and anti-inflammatory properties. In this study, we investigated the potential effects of CS on renal injury and fibrosis in a murine model of unilateral ureteral obstruction (UUO). Male C57BL/6J mice underwent sham or UUO surgery and received intraperitoneal injections of CS (50 mg/kg) daily for 8 consecutive days. CS improved renal function and ameliorated renal tubular injury and interstitial fibrosis in UUO mice. It suppressed oxidative injury by inhibiting pro-oxidant enzymes and activating antioxidant enzymes. Activation of ER stress was also attenuated by CS. In addition, CS inhibited apoptotic and necroptotic cell death in kidneys of UUO mice. Furthermore, cytokine production and immune cell infiltration were alleviated by CS. Taken together, these findings indicate that CS can attenuate renal injury and fibrosis in the UUO model.