Multifaceted roles of trained immunity in diverse pathological contexts.

Trained immunity, an innate immune response characterized by enhanced cellular responsiveness, exhibits a profound memory akin to adaptive immunity. This phenomenon involves intricate metabolic and epigenetic reprogramming triggered by stimuli such as ß-glucan and BCG, shaping innate immune memory. Following elucidation of the background on trained immunity, it is important to explore its multifaceted roles in various pathological contexts. In this review, we delve into the specific contributions of trained immunity in the intricate landscape of viral infections, tumorigenesis, and diverse inflammatory diseases, shedding light on its potential as a therapeutic target, and offering comprehensive understanding of its broader immunological implications.

UAV aided virtual cooperative spectrum sensing for cognitive radio networks.

Cooperative spectrum sensing (CSS) involves multiple secondary users (SUs) reporting primary user (PU) channel sensing states to the fusion center (FC). However, the high overheads associated with multi-user CSS impose power limitations that limit its usefulness in unmanned aerial vehicle (UAV) networks. To address this challenge, we propose a virtual CSS, where a single UAV conducts CSS while following a circular flight trajectory in the air. The novelty of our approach is presenting a working frame structure for the UAV flight, including sensing and data transmission periods with further division of the sensing time into mini-sensing slots. In the virtual CSS, UAV performs local sensing decisions in each mini-slot and accumulates them for a final decision. The proposed virtual CSS scheme exploits sequential decision fusion (SDF), which sequentially adds individual mini-slot decisions. Additionally, we leverage machine learning (ML), employing AdaBoost ensembling classifier (ENC), to inspect flight conditions and reconfigure mini-slot periods dynamically for both traditional decision fusion (TDF) and our proposed SDF schemes. Furthermore, we identify an optimal decision threshold (ODT) for the proposed SDF, enabling the comparison of sequential results with an adjustable threshold through majority voting. This novel approach results in energy efficiency and improved throughput for virtual CSS using SDF, surpassing the performance of TDF, which relies on collecting entire mini-slot reports for its final decision. Simulation results demonstrate the effectiveness of the proposed SDF following the ENCODT (SDF-ENCODT) scheme compared to existing techniques from the literature. We explore varying levels of UAV flight velocities, moving radius, detection probability demand, and channel signal-to-noise ratio (SNR), reinforcing the significance of our contribution. Our research highlights the motivation to address spectrum scarcity in UAV communication by proposing an innovative virtual CSS scheme based on SDF. The proposed approach enhances spectrum utilization, overcomes power limitations, and substantially improves CSS for UAV networks.

Using Real-Time Interaction Analysis to Explore Human-Robot Interaction.

Despite the increasing presence of social robots (SRs) in Human-Robot Interaction, there are few studies that quantify these interactions and explore children's attitudes by analyzing real-time data as they communicate with SRs. Therefore, we attempted to explore the interaction between pediatric patients and SRs by analyzing the interaction log collected from real-time. This study is a retrospective analysis of data collected in a prospective study conducted on 10 pediatric cancer patients at tertiary hospitals in Korea. Using the Wizard of Oz method, we collected the interaction log during the interaction between pediatric cancer patients and the robot. Out of the collected data, 955 sentences from the robot and 332 sentences from the children were available for analysis, except for the logs that were missing due to environmental errors. we analyzed the delay time from saving the interaction log and the sentence similarity of the interaction log. The interaction log delay time between robot and child was 5.01 seconds. And the child's delay time averaged 7.2 seconds, which was longer than the robot's delay time of 4.29 seconds. Additionally, as a result of analyzing the sentence similarity of the interaction log, the robot (97.2%) was higher than the children (46.2%). The results of the sentiment analysis of the patient's attitude toward the robot were 73% neutral, 13.59% positive, and 12.42% negative. The observational evaluations of pediatric psychological experts identified curiosity (n=7, 70.0%), activity (n=5, 50.0%), passivity (n=5, 50.0%), sympathy (n=7, 70.0%), concentration (n=6, 60.0%), high interest (n=5, 50.0%), positive attitude (n=9, 90.0%), and low interaction initiative (n=6, 60.0%). This study made it possible to explore the feasibility of interaction with SRs and to confirm differences in attitudes toward robots according to child characteristics. To increase the feasibility of human-robot interaction, measures such as improving the completeness of log records by enhancing the network environment are required.

Head and neck dermatitis is exacerbated by Malassezia furfur colonization, skin barrier disruption, and immune dysregulation.

Introduction & objectives: Head and neck dermatitis (HND) is a refractory phenotype of atopic dermatitis (AD) and can be a therapeutic challenge due to lack of responsiveness to conventional treatments. Previous studies have suggested that the microbiome and fungiome may play a role in inducing HND, but the underlying pathogenic mechanisms remain unknown. This study aimed to determine the link between HND and fungiome and to examine the contribution of Malassezia furfur. Materials and methods: To identify the effect of the sensitization status of M. furfur on HND, 312 patients diagnosed with AD were enrolled. To elucidate the mechanism underlying the effects of M. furfur, human keratinocytes and dermal endothelial cells were cultured with M. furfur and treated with Th2 cytokines. The downstream effects of various cytokines, including inflammation and angiogenesis, were investigated by real-time quantitative PCR. To identify the association between changes in lipid composition and M. furfur sensitization status, D-squame tape stripping was performed. Lipid composition was evaluated by focusing on ceramide species using liquid chromatography coupled with tandem mass spectrometry. Results: Increased sensitization to M. furfur was observed in patients with HND. Additionally, sensitization to M. furfur was associated with increased disease severity in these patients. IL-4 treated human keratinocytes cultured with M. furfur produced significantly more VEGF, VEGFR, IL-31, and IL-33. IL-4/M. furfur co-cultured dermal endothelial cells exhibited significantly elevated VEGFR, TGF-ß, TNF-α, and IL-1ß levels. Stratum corneum lipid analysis revealed decreased levels of esterified omega-hydroxyacyl-sphingosine, indicating skin barrier dysfunction in HND. Finally, M. furfur growth was inhibited by the addition of these ceramides to culture media, while the growth of other microbiota, including Cutibacterium acnes, were not inhibited. Conclusions: Under decreased levels of ceramide in AD patients with HND, M. furfur would proliferate, which may enhance pro-inflammatory cytokine levels, angiogenesis, and tissue remodeling. Thus, it plays a central role in the pathogenesis of HND in AD.

SOCS1 counteracts ROS-mediated survival signals and promotes apoptosis by modulating cell cycle to increase radiosensitivity of colorectal cancer cells.

As negative regulators of cytokine signaling pathways, suppressors of cytokine signaling (SOCS) proteins have been reported to possess both pro-tumor and anti-tumor functions. Our recent studies have demonstrated suppressive effects of SOCS1 on epithelial to mesenchymal signaling in colorectal cancer cells in response to fractionated ionizing radiation or oxidative stress. The objective of the present study was to determine the radiosensitizing action of SOCS1 as an anti-tumor mechanism in colorectal cancer cell model. In HCT116 cells exposed to ionizing radiation, SOCS1 over-expression shifted cell cycle arrest from G2/M to G1 and promoted radiation-induced apoptosis in a p53-dependent manner with down-regulation of cyclin B and up-regulation of p21. On the other hand, SOCS1 knock-down resulted in a reduced apoptosis with a decrease in G1 arrest. The regulatory action of SOCS1 on the radiation response was mediated by inhibition of radiation-induced Jak3/STAT3 and Erk activities, thereby blocking G1 to S transition. Radiation-induced early ROS signal was responsible for the activation of Jak3/Erk/STAT3 that led to cell survival response. Our data collectively indicate that SOCS1 can promote radiosensitivity of colorectal cancer cells by counteracting ROS-mediated survival signal, thereby blocking cell cycle progression from G1 to S. The resulting increase in G1 arrest with p53 activation then contributes to the promotion of apoptotic response upon radiation. Thus, induction of SOCS1 expression may increase therapeutic efficacy of radiation in tumors with low SOCS1 levels. [BMB Reports 2022; 55(4): 198-203].

Virus-like nanoparticles as a theranostic platform for cancer.

Virus-like nanoparticles (VLPs) are natural polymer-based nanomaterials that mimic viral structures through the hierarchical assembly of viral coat proteins, while lacking viral genomes. VLPs have received enormous attention in a wide range of nanotechnology-based medical diagnostics and therapies, including cancer therapy, imaging, and theranostics. VLPs are biocompatible and biodegradable and have a uniform structure and controllable assembly. They can encapsulate a wide range of therapeutic and diagnostic agents, and can be genetically or chemically modified. These properties have led to sophisticated multifunctional theranostic platforms. This article reviews the current progress in developing and applying engineered VLPs for molecular imaging, drug delivery, and multifunctional theranostics in cancer research.

A case of chronic lymphocytic leukemia masked by Cushing's disease in a dog.

A 12-year-old, 3.5-kg, intact female dog was presented with polyuria, polydipsia, and a pendulous abdomen. Laboratory examinations showed elevated hepatobiliary enzyme levels and neutrophilic leukocytosis. The adrenocorticotropic hormone stimulation test confirmed hyperadrenocorticism (HAC). Trilostane therapy managed the clinical condition and cortisol concentration. However, lymphocytosis and nonregenerative anemia developed after HAC remission. Bone marrow aspiration analysis revealed a lymphoproliferative disorder with a clonal T-cell population. Accordingly, the patient was diagnosed with T-cell chronic lymphocytic leukemia (CLL) and concurrent HAC. Thereafter, chemotherapy was initiated, which improved the lymphocytosis. However, euthanasia was performed because of worsening quality of life at 45 weeks after the first presentation. These results suggested that CLL could be masked by excessive endogenous cortisol and discovered after HAC remission.

Safe and feasible outcomes of cholecystectomy in extremely elderly patients (octogenarians vs. nonagenarians).

Purpose: Cholecystectomy is the gold standard treatment for gallbladder disease. As life expectancy increases, awareness of cholecystitis treatment in the elderly changes. The safety and feasibility of cholecystectomy in octogenarians have been proven in many studies. Surgical treatment for cholecystitis should be considered in octogenarians and even nonagenarians. In this study, we aimed to assess the outcomes of cholecystectomy in octogenarians and nonagenarians with acute cholecystitis. Methods: A total of 393 patients aged 80 to 89 years (352 octogenarians) and 90 to 99 years (41 nonagenarians) diagnosed with acute cholecystitis underwent cholecystectomy between March 2012 and June 2020. All patients were classified according to the Tokyo guidelines. The evaluated parameters included demographic data, surgical outcomes, American Society of Anesthesiologists physical status classification, and Tokyo guidelines. Results: All 393 patients were analyzed and divided into two groups according to age; octogenarians (83.57 ± 2.64 years) and nonagenarians (92.98 ± 3.15 years). The survival rate was 97.7% for octogenarians and 97.6% for nonagenarians. Laparoscopic surgery was performed more in both groups (96.8% in octogenarians and 92.7% in nonagenarians) than open surgery (3.2% in octogenarians and 7.3% in nonagenarians). The operation time of the nonagenarian group (74.63 ± 30.83 minutes) was shorter than the octogenarian group (75.85 ± 34.63 minutes). The incidences of postoperative complications in the octogenarian and nonagenarian groups were as follows pneumonia, 5.7% and 7.3%; bleeding, 1.7% and 2.4%; gastrointestinal symptoms, 6.0% and 2.4%; and bile leakage, 0.6% and 2.4%, respectively. Conclusion: Cholecystectomy is a safe and efficient procedure for the treatment of acute cholecystitis in both octogenarians and nonagenarians.

Non-Ablative 1927 nm Fractional Thulium Fiber Laser: New, Promising Treatment Modality for Riehl's Melanosis.

BACKGROUND AND OBJECTIVES: The treatment of Riehl's melanosis, also known as pigmented contact dermatitis, is highly challenging. Intense pulsed light (IPL) and 1064 nm Q-switched Nd:Yag (QS-Nd:YAG) laser are reported to have some efficacy. However, no single effective treatment has yet been identified. In this study, we demonstrated the efficacy and safety of the non-ablative 1927 nm fractional thulium fiber laser (TFL, LASEMD™; Lutronic Corp., Goyang, Korea) for patients with Riehl's melanosis. STUDY DESIGN/MATERIALS AND METHODS: A retrospective chart and photographic review of nine patients with Riehl's melanosis, who had received at least three sessions of TFL treatment, was performed. Before the start of TFL treatment, combination treatment with a topical cream containing hydroquinone, low-fluence QS-Nd:YAG laser, pulsed dye laser, and IPL was used with variable and discouraging effects. Seven patients were treated on the face and two patients on the neck with three to seven sessions at 1-month intervals. Clinical improvement was assessed using clinical photos taken before and after every treatment session according to dermal pigmentation area and severity index (DPASI) and a quartile grading scale by two blinded dermatologists. RESULTS: Patients underwent three to seven sessions of TFL treatment depending on severity of pigmentation. Of nine patients, six demonstrated a clinical improvement of 51%-75%, one demonstrated an improvement of 76%-100%, and two showed an improvement of 26%-50% after treatment. The DPASI was significantly decreased from 9.55 to 5.25 on average. Melanin index was decreased after treatment in two patients whose melanin index were measured at initial visits. Treatment-related adverse events, such as scarring or postinflammatory hyperpigmentation (PIH), were not observed in all patients except for transient erythema and swelling. CONCLUSIONS: This report suggests that TFL could be an alternative and/or additive treatment option for hyperpigmentation in intractable Riehl's melanosis and might be a promising treatment for PIH caused by any reason including Riehl's melanosis. Lasers Surg. Med. © 2020 Wiley Periodicals LLC.

A Prospective, Split-Face, Comparative Study of Combined Treatment With Fractional Microneedle Radiofrequency and Nonablative 1927-nm Fractional Thulium Fiber Laser for Wrinkle Treatment.

BACKGROUND: Fractional microneedle radiofrequency (FMR) and nonablative 1927-nm fractional thulium fiber laser (TFL) are widely used for skin rejuvenation treatment. OBJECTIVES: To investigate the efficacy and safety of combined treatment with both devices for wrinkles. PATIENTS AND METHODS: Twenty-five patients with wrinkles were enrolled. One side of the face was treated with FMR alone, while the other side was treated with a combination of FMR and TFL. Each treatment consisted of 3 sessions at four-week intervals and patients were followed up 12 weeks after the last treatment. Overall improvement was assessed by patient global assessment (PGA) and investigator global assessment (IGA). Depression scores for the evaluation of wrinkles were objectively assessed by Antera 3D system. RESULTS: Both sides of the face led to clinical improvement in both mean PGA and IGA. Combination treatment demonstrated a greater improvement in both mean PGA and IGA compared with FMR alone. In addition, wrinkle grading scales and depression scores showed greater improvement in the combination group than in FMR alone. CONCLUSION: This study demonstrated that FMR and TFL comprise a good combination treatment for the treatment of wrinkles because both treatments have a synergistic effect on wrinkle improvement.

Ewing sarcoma protein promotes dissociation of poly(ADP-ribose) polymerase 1 from chromatin.

Poly(ADP-ribose) polymerase 1 (PARP1) facilitates DNA damage response (DDR). While the Ewing's sarcoma breakpoint region 1 (EWS) protein fused to FLI1 triggers sarcoma formation, the physiological function of EWS is largely unknown. Here, we investigate the physiological role of EWS in regulating PARP1. We show that EWS is required for PARP1 dissociation from damaged DNA. Abnormal PARP1 accumulation caused by EWS inactivation leads to excessive Poly(ADP-Ribosy)lation (PARylation) and triggers cell death in both in vitro and in vivo models. Consistent with previous work, the arginine-glycine-glycine (RGG) domain of EWS is essential for PAR chain interaction and PARP1 dissociation from damaged DNA. Ews and Parp1 double mutant mice do not show improved survival, but supplementation with nicotinamide mononucleotides extends Ews-mutant pups' survival, which might be due to compensatory activation of other PARP proteins. Consistently, PARP1 accumulates on chromatin in Ewing's sarcoma cells expressing an EWS fusion protein that cannot interact with PARP1, and tissues derived from Ewing's sarcoma patients show increased PARylation. Taken together, our data reveal that EWS is important for removing PARP1 from damaged chromatin.

Efficacy of Olanzapine for High and Moderate Emetogenic Chemotherapy in Children.

This study was conducted to investigate the safety and efficacy of olanzapine for high and moderate emetogenic chemotherapy in children and young adults. We retrospectively reviewed the records of pediatric patients (n = 13) with cancer who had been administered olanzapine as an anti-emetic drug (AED) during a high and moderate emetogenic chemotherapy block from January 2018 to March 2020. Patients were administered other prophylactic AEDs according to practice guidelines. The mean age of the patients was 14.1 ± 5.5 years. The total number of chemotherapy cycles was 41. Twenty-one (51.2%) chemotherapy blocks were high emetogenic chemotherapy and 20 (48.8%) blocks were moderate emetogenic chemotherapy. Olanzapine was used for prophylaxis in 20 (48.8%) blocks of chemotherapy and rescue in 21 (51.2%). Of the 41 cycles, a complete response to olanzapine was achieved in 31 (75.6%), partial response in 6 (14.6%), and no response in 4 (9.8%). The mean dose was 0.07 ± 0.04 mg/kg/dose and 2.50 ± 1.37 mg/m2/dose. Adverse effects included somnolence, hyperglycemia, fatigue, and disturbed sleep. Our findings indicate that olanzapine was effective and safe for treating chemotherapy-induced nausea and vomiting in children. A prospective controlled study is needed to confirm these findings.

A comparative study of three different surgical methods for both-forearm-bone fractures in adults.

The purpose of this study was to evaluate and compare the results of plate osteosynthesis, intramedullary nailing (IMN), and hybrid fixation for the treatment of both-forearm-bone shaft fractures in adults. One-hundred-one cases of both-forearm-bone shaft fractures were retrospectively reviewed. All fractures were divided into the following three groups, according to the method used for internal fixation : open reduction and internal fixation ORIF group (plate osteosynthesis), IMN group, and HYBRID group (plate osteosynthesis for the radius and intramedullary nail for the ulna). The results were assessed based on the time to union, functional recovery, restoration of the ulna and radial bow, operating time, complications, and patient satisfaction. In the ORIF, IMN, and HYBRID groups, the average union time was 10.8, 14.9, and 11.5 weeks, respectively. No intergroup differences were observed in the functional outcomes. The ORIF and HYBRID groups had a significantly better radial bow ratio compared to the IMN group. All patients in the three groups achieved union, with the exception of a single case of nonunion in the IMN group. ORIF and HYBRID fixation resulted in a more anatomical restoration of radial bow ratio, compared to the contralateral side. Such significant differences in the restoration of the radial bow had no effect on the final functional outcomes and minimal effect on forearm range of motion. Although there are statistically significant effects on the final forearm range of motion, the difference was only 5°. Thus, if the indication is properly selected, our results suggest that hybrid fixation would be acceptable and effective treatment options for both-forearm-bone fractures in adults.

Gallotannin attenuates 2­deoxy­D­glucose­induced dedifferentiation and endoplasmic reticulum stress through inhibition of inositol­requiring enzyme 1 downstream p38 kinase pathway in chondrocytes.

Gallotannin (GT) is a class of polyphenols with antioxidant, anticancer, and antiviral activities. 2­Deoxy­D­glucose (2DG), a glucose­derived molecule, can inhibit glucose metabolism and induce endoplasmic reticulum (ER) stress. GT in primary­cultured chondrocytes enhances expression of type II collagen, an indicator of differentiation, and cyclooxygenase­2 (COX­2), which mediates inflammatory reactions. In contrast, 2DG reduces type II collagen and COX­2 expression while driving ER­stress­induced unglycosylation. In the present study, it was investigated whether GT could attenuate 2DG­induced dedifferentiation and ER­stress. Following treatment with GT and 2DG, chondrocytes were assessed using western blotting, RT­PCR, immunofluorescence, and alcian blue staining. GT restored type II collagen expression that was reduced by 2DG, inhibited ER­stress­induced COX­2 unglycosylation, and induced COX­2 expression. The expression of a glucose­regulated protein, GRP78, which is an indicator of reduced ER­stress, was decreased. To link the GT signaling pathway with pathways that inhibit 2DG­induced dedifferentiation and ER­stress, inhibitors were treated in chondrocytes. The results revealed that, among the different signaling pathways triggered by ER­stress, the p38 kinase pathway was involved in the inositol­requiring enzyme 1 (IRE1) downstream signaling pathway. Following inhibition of the IRE1 pathway, type II collagen expression was increased and COX­2 expression was decreased. In addition, after examining the splicing of X­box binding protein 1 (XBP­1) which is dependent on IRE1 activation induced by ER­stress, it was revealed that GT inhibited the increase of XBP­1s after splicing due to 2DG­induced ER stress. GT in chondrocytes inhibited 2DG­induced dedifferentiation and ER­stress­induced COX­2 unglycosylation while regulating differentiation and inflammation via the ER­stress­induced p38 kinase pathway downstream from the IRE1 pathway.

Effects of α-lipoic acid on LPS-induced neuroinflammation and NLRP3 inflammasome activation through the regulation of BV-2 microglial cells activation.

Microglial cells are known as the main immune cells in the central nervous system, both regulating its immune response and maintaining its homeostasis. Furthermore, the antioxidant α-lipoic acid (LA) is a recognized therapeutic drug for diabetes because it can easily invade the blood-brain barrier. This study investigated the effect of α-LA on the inflammatory response in lipopolysaccharide (LPS)-treated BV-2 microglial cells. Our results revealed that α-LA significantly attenuated several inflammatory responses in BV-2 microglial cells, including pro-inflammatory cytokines, such as tumor necrosis factor-α and interleukin (IL)-6, and other cytotoxic molecules, such as nitric oxide and reactive oxygen species. In addition, α-LA inhibited the LPS-induced phosphorylation of ERK and p38 and its pharmacological properties were facilitated via the inhibition of the nuclear factor kappa B signaling pathway. Moreover, α-LA suppressed the activation of NOD-like receptor pyrin domain containing 3 (NLRP3) inflammasomes, multiprotein complexes consisting of NLRP3 and caspase-1, which are involved in the innate immune response. Finally, α-LA decreased the genes accountable for the M1 phenotype, IL-1ß and ICAM1, whereas it increased the genes responsible for the M2 phenotype, MRC1 and ARG1. These findings suggest that α-LA alleviates the neuroinflammatory response by regulating microglial polarization. [BMB Reports 2019; 52(10): 613-618].

Hypoxia Upregulates Mitotic Cyclins Which Contribute to the Multipotency of Human Mesenchymal Stem Cells by Expanding Proliferation Lifespan.

Hypoxic culture is widely recognized as a method to efficiently expand human mesenchymal stem cells (MSCs) without loss of stem cell properties. However, the molecular basis of how hypoxia priming benefits MSC expansion remains unclear. In this report, our systemic quantitative proteomic and RT-PCR analyses revealed the involvement of hypoxic conditioning activated genes in the signaling process of the mitotic cell cycle. Introduction of screened two mitotic cyclins, CCNA2 and CCNB1, significantly extended the proliferation lifespan of MSCs in normoxic condition. Our results provide important molecular evidence that multipotency of human MSCs by hypoxic conditioning is determined by the mitotic cell cycle duration. Thus, the activation of mitotic cyclins could be a potential strategy to the application of stem cell therapy.

Protective effect of 3-(naphthalen-2-yl(propoxy)methyl)azetidine hydrochloride on hypoxia-induced toxicity by suppressing microglial activation in BV-2 cells.

We recently reported the anti-inflammatory effects of 3-(naphthalen-2-yl(propoxy)methyl)azetidine hydrochloride (KHG26792) on the ATP-induced activation of the NFAT and MAPK pathways through the P2X7 receptor in microglia. To further investigate the underlying mechanism of KHG26792, we studied its protective effects on hypoxia-induced toxicity in microglia. The administration of KHG26792 significantly reduced the hypoxia-induced expression and activity of caspase-3 in BV-2 microglial cells. KHG26792 also reduced hypoxia-induced inducible nitric oxide synthase protein expression, which correlated with reduced nitric oxide accumulation. In addition, KHG26792 attenuated hypoxiainduced protein nitration, reactive oxygen species production, and NADPH oxidase activity. These effects were accompanied by the suppression of hypoxia-induced protein expression of hypoxia-inducible factor 1-alpha and NADPH oxidase-2. Although the clinical relevance of our findings remains to be determined, these data results suggest that KHG26792 prevents hypoxia-induced toxicity by suppressing microglial activation. [BMB Reports 2016; 49(12): 687-692].

Mechanism of suppressors of cytokine signaling 1 inhibition of epithelial-mesenchymal transition signaling through ROS regulation in colon cancer cells: suppression of Src leading to thioredoxin up-regulation.

Reactive oxygen species (ROS) participate in malignant progression of cancers including epithelial-mesenchymal transition (EMT). We have investigated the role of suppressors of cytokine signaling (SOCS)1 as an inhibitor of ROS-induced EMT using colon cancer cell lines transduced with SOCS1 and shSOCS1. Hydrogen peroxide treatment induced EMT features such as elevation of vimentin and Snail with a corresponding reduction of E-cadherin. The EMT markers are significantly decreased upon SOCS1 over-expression while increased under SOCS1 knock-down. SOCS1 inhibited ROS signaling pathways associated with EMT such as Src, Jak, and p65. Of note, strong up-regulation of Src activity in SOCS1-ablated cells was responsible for the elevated signaling leading to EMT, as shSrc or Src inhibitor abolished the shSOCS1-induced promotion of EMT response. Suppression of ROS-inducible EMT markers and invasion in SOCS1 over-expressing cells correlated with significantly low intracellular ROS levels in these cells. Analysis of antioxidant enzymes in SOCS1-transduced cells revealed a selective up-regulation of thioredoxin (Trx1), while thioredoxin ablation restored ROS levels and the associated EMT markers. As a mechanism of thioredoxin up-regulation by SOCS1, inhibition of Src activity promoting nuclear translocation of Nrf-2 is proposed. Taken together, our data strongly indicate that SOCS1 antagonizes EMT by suppressing Src activity, leading to thioredoxin expression and down-regulation of ROS levels in colon cancer cells.

Primary diffuse malignant peritoneal mesothelioma in a striped skunk (Mephitis mephitis).

A 10-year-old female striped skunk (Mephitis mephitis) was admitted with severe abdominal distension and lethargy. Cytological examination of the peritoneal fluid revealed activated mesothelial cells. At necropsy, numerous growing together, projecting, 2 to 20 mm in diameter tawny to white masses were scattered throughout the peritoneum including the mesentery, omentum and intestinal serosa. Microscopically, the tumor was composed of prominent papillo-tubular structures, and immunohistochemically, the spindle to polygonal-shaped tumor cells with nuclear polymorphism were strongly reactive for calretinin. Based on those diagnostic features, the neoplasia was diagnosed as malignant mesothelioma. This is the first case report of mesothelioma in the skunk.

Multiple classes of immune-related proteases associated with the cell death response in pepper plants.

Proteases regulate a large number of biological processes in plants, such as metabolism, physiology, growth, and defense. In this study, we carried out virus-induced gene silencing assays with pepper cDNA clones to elucidate the biological roles of protease superfamilies. A total of 153 representative protease genes from pepper cDNA were selected and cloned into a Tobacco rattle virus-ligation independent cloning vector in a loss-of-function study. Silencing of 61 proteases resulted in altered phenotypes, such as the inhibition of shoot growth, abnormal leaf shape, leaf color change, and lethality. Furthermore, the silencing experiments revealed that multiple proteases play a role in cell death and immune response against avirulent and virulent pathogens. Among these 153 proteases, 34 modulated the hypersensitive cell death response caused by infection with an avirulent pathogen, and 16 proteases affected disease symptom development caused by a virulent pathogen. Specifically, we provide experimental evidence for the roles of multiple protease genes in plant development and immune defense following pathogen infection. With these results, we created a broad sketch of each protease function. This information will provide basic information for further understanding the roles of the protease superfamily in plant growth, development, and defense.