Search

Background: As the number of people working from home has increased since the COVID-19 pandemic, it is important to understand workers’ stress and psychological state while working from home. Work-family conflict and loneliness may be related to working from home, and they could be experienced differently depending on individual traits. Therefore, this study examined the parallel multiple mediating effects of work-family conflict and loneliness in the relationship between personal temperaments and negative emotions such as depression and anxiety.Methods: Data were collected online from people currently working from home for at least one month, more than once per week. They answered K-DASS-21, UCLA loneliness scale, Work-Family Conflict, and FCB-TI. Only four temperaments were used in the statistic step: Briskness and Sense sensitivity as protective factors and Perseveration and Emotional reactivity as vulnerable factors. The multiple mediating effects were analyzed independently by using the PROCESS macro.Results: Firstly, Briskness and Sense sensitivity were found to negatively affect depression and anxiety while working from home by significantly mediating work-family conflict and loneliness. Thus, these temperaments would be protective factors while working from home. Secondly, Perseveration and Emotional reactivity positively influenced both negative emotions by mediating two mediation variables, which means that both temperaments are vulnerable factors.Conclusions: The results suggest that personality traits can impact how people experience stress and negative emotions in working situations, leading to negative psychological states. Consequently, personal temperaments would be important to understand relationships between environments and internal experiences.

Background: Temperament plays an important role in adapting to different environments. The purpose of this study is to investigate the differences between temperament clusters, time management behavior, quality of life, and work-life balance.Methods: A total of 216 participants (male=56, female=160, mean age: 31.92 years) completed questionnaires measuring temperament, time management behavior, quality of life, and work-life balance.Results: Data from the study shows that temperamental profiles are classified into three groups. The profile of “Adaptive Solver” was associated with the most beneficial traits, and that of “Chronic Worrier” was associated with the most disadvantageous traits.Conclusions: The findings of this study confirm that temperaments are related to psychological adjustment. This study provides an implication for considering individual differences in the intervention for psychological adaptation of workers.

Myelin water imaging (MWI) using MRI has been introduced as a method to quantify the integrity of myelin in vivo. However, the investigation of its potential to probe myelin changes has been limited.To determine the myelin change using MWI in the corticospinal tract (CST) during the rehabilitation of stroke patients.Longitudinal.A total of 24 stroke patients within 6 months from the onset (64.3 ± 16.1 years, 14 women, 10 men) and 10 healthy volunteers (27.0 ± 2.2 years, 2 women, 8 men).Three-dimensional multiecho gradient echo sequence and diffusion-weighted echoplanar imaging sequence at 3 T.The changes of myelin water fraction (MWF) and fractional anisotropy (FA) during rehabilitation were analyzed in the CST and other regions using tractography software and region of interest drawings by the radiologist.A paired t-test was performed to investigate the change of MRI metrics during rehabilitation. In addition, an independent two-sample t-test was performed to investigate the effects of different rehabilitation protocols. A P-value0.05 was considered significant.In the CST, MWF significantly changed from 5.83 ± 0.91% to 6.23 ± 0.97% after rehabilitation while changes of FA (0.442 ± 0.038 to 0.443 ± 0.035) were not significant (P = 0.656). The rate of change in MWF and FA, which were 6.69% and 0.439% respectively, were significantly different. Other regions did not show significant changes (range of MWF change: -3.44% to -1.61%, range of FA change: -1.39% to 0.79%, and range of P-value: 0.144-0.761). Further analysis showed that those with additional robot-assisted rehabilitation had a significantly larger MWF change than those with conventional rehabilitation only (rate of change: 11.2% vs. 3.2%).The feasibility of using MWI to monitor myelin content was demonstrated by showing the MWF changes during rehabilitation.2 TECHNICAL EFFICACY STAGE: 2.

Liver fibrosis is part of the wound healing process to help the liver recover from the injuries caused by various liver-damaging insults. However, liver fibrosis often progresses to life-threatening cirrhosis and hepatocellular carcinoma. To overcome the limitations of current in vivo liver fibrosis models for studying the pathophysiology of liver fibrosis and establishing effective treatment strategies, we developed a new mouse model of liver fibrosis using polyhexamethylene guanidine phosphate (PHMG-p), a humidifier sterilizer known to induce lung fibrosis in humans. Male C57/BL6 mice were intraperitoneally injected with PHMG-p (0.03% and 0.1%) twice a week for 5 weeks. Subsequently, liver tissues were examined histologically and RNA-sequencing was performed to evaluate the expression of key genes and pathways affected by PHMG-p. PHMG-p injection resulted in body weight loss of ~15% and worsening of physical condition. Necropsy revealed diffuse fibrotic lesions in the liver with no effect on the lungs. Histology, collagen staining, immunohistochemistry for smooth muscle actin and collagen, and polymerase chain reaction analysis of fibrotic genes revealed that PHMG-p induced liver fibrosis in the peri-central, peri-portal, and capsule regions. RNA-sequencing revealed that PHMG-p affected several pathways associated with human liver fibrosis, especially with upregulation of lumican and IRAK3, and downregulation of GSTp1 and GSTp2, which are closely involved in liver fibrosis pathogenesis. Collectively we demonstrated that the PHMG-p-induced liver fibrosis model can be employed to study human liver fibrosis.

ObjectiveGastric cancer (GC) is a leading cause of cancer-related mortality. Although microbes besides Helicobacter pylori may also contribute to gastric carcinogenesis, wild-type germ-free (GF) mouse models investigating the role of human gastric microbiota in the process are not yet available. We aimed to evaluate the histopathological features of GF mouse stomachs transplanted with gastric microbiota from patients with different gastric disease states and their relationships with the microbiota.DesignMicrobiota profiles in corpus and antrum tissues and gastric fluid from 12 patients with gastric dysplasia or GC were analysed. Thereafter, biopsied corpus and antrum tissues and gastric fluid from patients (n=15 and n=12, respectively) with chronic superficial gastritis, intestinal metaplasia or GC were inoculated into 42 GF C57BL/6 mice. The gastric microbiota was analysed by amplicon sequencing. Histopathological features of mouse stomachs were analysed immunohistochemically at 1 month after inoculation. An independent set of an additional 15 GF mice was also analysed at 1 year.ResultsThe microbial community structures of patients with dysplasia or GC in the corpus and antrum were similar. The gastric microbiota from patients with intestinal metaplasia or GC selectively colonised the mouse stomachs and induced premalignant lesions: loss of parietal cells and increases in inflammation foci, in F4/80 and Ki-67 expression, and in CD44v9/GSII lectin expression. Marked dysplastic changes were noted at 1 year post inoculation.ConclusionMajor histopathological features of premalignant changes are reproducible in GF mice transplanted with gastric microbiota from patients with intestinal metaplasia or GC. Our results suggest that GF mice are useful for analysing the causality of associations reported in human gastric microbiome studies.

Strains of Helicobacter pylori that are positive for the oncoprotein CagA (cytotoxin-associated gene A) are associated with gastric cancer and might be related to the epithelial-to-mesenchymal transition (EMT). Casein kinase 2 (CK2) is a serine/threonine protein kinase that plays a major role in tumorigenesis through signaling pathways related to the EMT. However, the role played by the interaction between CagA and CK2 in gastric carcinogenesis is poorly understood. Although CK2α protein expression remained unchanged during H. pylori infection, we found that CK2α kinase activity was increased in gastric epithelial cells. We also found that the CK2β protein level decreased in H. pylori-infected gastric cancer cells in CagA-dependent manner and demonstrated that CagA induced CK2β degradation via HDM2 (human double minute 2; its murine equivalent is MDM2). We observed that CagA induced HDM2 protein phosphorylation and that p53 levels were decreased in H. pylori-infected gastric cancer cells. In addition, downregulation of CK2β induced AKT Ser473 phosphorylation and decreased the AKT Ser129 phosphorylation level in gastric cancer cells. We also found that the downregulation of CK2β triggered the upregulation of Snail levels in gastric cancer cells. Furthermore, our in vivo experiments and functional assays of migration and colony formation suggest that CK2β downregulation is a major factor responsible for the EMT in gastric cancer. Therefore, CK2 could be a key mediator of the EMT in H. pylori-infected gastric cancer and could serve as a molecular target for gastric cancer treatment.

The lesion detection rate of esophagogastroduodenoscopy (EGD) varies depending on the degree of experience of the endoscopist and anatomical blind spots. This study aimed to identify gaze patterns and blind spots by analyzing the endoscopist’s gaze during real-time EGD. Five endoscopists were enrolled in this study. The endoscopist’s eye gaze tracked by an eye tracker was selected from the esophagogastric junction to the second portion of the duodenum without the esophagus during insertion and withdrawal, and then matched with photos. Gaze patterns were visualized as a gaze plot, blind spot detection as a heatmap, observation time (OT), fixation duration (FD), and FD-to-OT ratio. The mean OT and FD were 11.10 ± 11.14 min and 8.37 ± 9.95 min, respectively, and the FD-to-OT ratio was 72.5%. A total of 34.3% of the time was spent observing the antrum. When observing the body of the stomach, it took longer to observe the high body in the retroflexion view and the low-to-mid body in the forward view. It is necessary to minimize gaze distraction and observe the posterior wall in the retroflexion view. Our results suggest that eye-tracking techniques may be useful for future endoscopic training and education.

Theranostic, which integrates the diagnosis and tumor treatment in tandem, is an emerging strategy in cancer treatment. Here, we report a novel and unique theranostic nanoparticle, HBCP NP, based on hexa-BODIPY cyclophosphazene (HBCP). Due to the unique bulky molecular structure of HBCP, this nanoparticle can simultaneously perform near-infrared (NIR) fluorescence imaging and photoacoustic imaging (PAI). Interestingly, since reactive oxygen species (ROS) generation of HBCP NPs is completely inhibited, 'safe' fluorescence imaging is possible without the risk of cell damage even under laser irradiation. Finally, NIR fluorescence imaging and PAI in 4T1 tumor-bearing mice demonstrated selective accumulation of HBCP NPs at tumor sites. In addition, HBCP NPs exhibited excellent photothermal effects under high-power laser irradiation, achieving effective tumor growth inhibition.

Approximately 70% of breast cancers are estrogen receptor (ER)-positive and treated with endocrine therapy. A commonly used treatment agent, tamoxifen, shows high efficacy for improving prognosis. However, approximately one-third of patients treated with tamoxifen develop resistance to this drug. Here, we investigated the function of general control non-derepressible 5 (GCN5) and its downstream effectors in tamoxifen-resistant (TamR) breast cancer. TamR-MCF7 breast cancer cells maintained high GCN5 levels due to its attenuated proteasomal degradation. GCN5 overexpression upregulated amplified in breast cancer 1 (AIB1) expression, resulting in decreased p53 stability and tamoxifen resistance. Conversely, the sensitivity of GCN5-AIB1-overexpressing MCF7 cells to tamoxifen was restored by forced p53 expression. An in vivo study demonstrated a positive correlation between GCN5 and AIB1 and their contribution to tamoxifen resistance. We concluded that GCN5 promotes AIB1 expression and tamoxifen resistance in breast cancer by reducing p53 levels, suggesting the utility of GCN5 and its downstream effectors as therapeutic targets to either prevent or overcome tamoxifen resistance in breast cancer.

An effective strategy to engineer selective photodynamic agents to surmount bacterial-infected diseases, especially Gram-positive bacteria remains a great challenge. Herein, we developed two examples of compounds for a proof-of-concept study where reactive differences in reactive oxygen species (ROS) can induce selective ablation of Gram-positive bacteria. Sulfur-replaced phenoxazinium (NBS-N) mainly generates a superoxide anion radical capable of selectively killing Gram-positive bacteria, while selenium-substituted phenoxazinium (NBSe-N) has a higher generation of singlet oxygen that can kill both Gram-positive and Gram-negative bacteria. This difference was further evidenced by bacterial fluorescence imaging and morphological changes. Moreover, NBS-N can also successfully heal the Gram-positive bacteria-infected wounds in mice. We believe that such reactive differences may pave a general way to design selective photodynamic agents for ablating Gram-positive bacteria-infected diseases.

This study investigated the efficacy and safety of convalescent plasma (CP) transfusion against the coronavirus disease 2019 (COVID-19) via a systematic review and meta-analysis of randomized controlled trials (RCTs). A total of 5467 articles obtained from electronic databases were assessed; however, only 34 RCTs were eligible after manually screening and eliminating unnecessary studies. The beneficial effect was addressed by assessing the risk ratio (RR) and standardized mean differences (SMDs) of the meta-analysis. It was demonstrated that CP therapy is not effective in improving clinical outcomes, including reducing mortality with an RR of 0.88 [0.76; 1.03] (I2 = 68% and p = 0.10) and length of hospitalization with SMD of −0.47 [−0.95; 0.00] (I2 = 99% and p = 0.05). Subgroup analysis provided strong evidence that CP transfusion does not significantly reduce all-cause mortality compared to standard of care (SOC) with an RR of 1.01 [0.99; 1.03] (I2 = 70% and p = 0.33). In addition, CP was found to be safe for and well-tolerated by COVID-19 patients as was the SOC in healthcare settings. Overall, the results suggest that CP should not be applied outside of randomized trials because of less benefit in improving clinical outcomes for COVID-19 treatment.

Viperin is an interferon (IFN)-inducible multifunctional protein. Recent evidence from high-throughput analyses indicates that most IFN-inducible proteins, including viperin, are intrinsically expressed in specific tissues; however, the respective intrinsic functions are unknown. Here we show that the intrinsic expression of viperin regulates adipose tissue thermogenesis, which is known to counter metabolic disease and contribute to the febrile response to pathogen invasion. Viperin knockout mice exhibit increased heat production, resulting in a reduction of fat mass, improvement of high-fat diet (HFD)-induced glucose tolerance, and enhancement of cold tolerance. These thermogenic phenotypes are attributed to an adipocyte-autonomous mechanism that regulates fatty acid β-oxidation. Under an HFD, viperin expression is increased, and its function is enhanced. Our findings reveal the intrinsic function of viperin as a novel mechanism regulating thermogenesis in adipose tissues, suggesting that viperin represents a molecular target for thermoregulation in clinical contexts.

Acetaminophen (APAP) overdose can cause hepatotoxicity by inducing mitochondrial damage and subsequent necrosis in hepatocytes. Sirtuin2 (Sirt2) is an NAD+-dependent deacetylase that regulates several biological processes, including hepatic gluconeogenesis, as well as inflammatory pathways. We show that APAP decreases the expression of Sirt2. Moreover, the ablation of Sirt2 attenuates APAP-induced liver injuries, such as oxidative stress and mitochondrial damage in hepatocytes. We found that Sirt2 deficiency alleviates the APAP-mediated endoplasmic reticulum (ER) stress and phosphorylation of the p70 ribosomal S6 kinase 1 (S6K1). Moreover, Sirt2 interacts with and deacetylates S6K1, followed by S6K1 phosphorylation induction. This study elucidates the molecular mechanisms underlying the protective role of Sirt2 inactivation in APAP-induced liver injuries. [BMB Reports 2019; 52(3): 190-195].

Multidrug-resistant (MDR) gram-positive bacteria are an inevitable source of infection for hospitalized patients and one of the reasons for the increased proportion of severe diseases. Therefore, constructing smart agents for specific and effective combating infections in vivo caused by MDR gram-positive strains is very urgent. Herein, we reported a structure-oriented design strategy (SODS) to reasonably construct an organic photo-antimicrobial near-infrared (NIR) AIEgen BDPTV equipped with a phenylboronic acid moiety, which could be bound to the thick peptidoglycan layer of MDR gram-positive bacteria, resulting in a tight distribution with the cell wall in a confined space. Compared to the contrast compounds DQVTA and DPTVN, upon photoirradiation of AIEgen BDPTV, the generation of abundant and highly toxic reactive oxygen species (ROS) irreversibly destroys MDR gram-positive bacteria through photodynamic therapy, which is better than commercial photosensitizers (including methylene blue, chlorin e6, and protoporphyrin IX) and antibiotic (cefoxitin). As a proof of concept, in vitro experimental results showed that methicillin-resistant Staphylococcus aureus (MRSA) were completely killed using AIEgen BDPTV. More importantly, AIEgen BDPTV was capable of successfully combating MRSA-infected wounds of mice, but not Escherichia coli (E. coli)-infected wounds. We hope that this strategy could provide a new method to design powerful AIEgens to avoid the overuse and misuse of antibiotics.

Trefoil factor 1 (TFF1, also known as pS2) is strongly expressed in the gastrointestinal mucosa and plays a critical role in the differentiation of gastric glands. Since approximately 50% of all human gastric cancers are associated with decreased TFF1 expression, it is considered a tumor suppressor gene. Tff1 deficiency in mice results in histological changes in the antral and pyloric gastric mucosa, with severe hyperplasia and dysplasia of epithelial cells, resulting in the development of antropyloric adenoma. Here, we generated Tff1-knockout (KO) mice, without a neomycin resistant (NeoR) cassette, using the clustered regularly interspaced short palindromic repeats/CRISPR-associated nuclease 9 (CRSIPR/Cas9) system. Though our Tff1-KO mice showed phenotypes very similar to the previous embryonic stem (ES)-cell-based KO mice, they differed from the previous reports in that a reduction in body weight was observed in males. These results demonstrate that these newly established Tff1-KO mice are useful tools for investigating genetic and environmental factors influencing gastric cancer, without the effects of artificial gene insertion. Furthermore, these findings suggest a novel hypothesis that Tff1 expression influences gender differences.

Leucine-rich repeats and immunoglobulin-like domains (LRIG)-1 is a transmembrane protein that antagonizes epidermal growth factor receptor signaling in epithelial tissues. LRIG1 is down-regulated in various epithelial cancers, including bladder, breast, and colorectal cancer, suggesting that it functions as a tumor suppressor. However, its role in gastric carcinogenesis is not well understood. Here, we investigated the changes in LRIG1 expression during the stages of gastric cancer. We used a DMP-777–induced spasmolytic polypeptide-expressing metaplasia mouse model and a tissue array of human gastric cancer lesions. The effects of LRIG1 knockdown were also assessed using the human gastric cancer cell line SNU638 in a xenograft model. LRIG1 expression varied over the course of gastric carcinogenesis, increasing in spasmolytic polypeptide-expressing metaplasia lesions but disappearing in intestinal metaplasia and cancer lesions, and the increase was concurrent with the up-regulation of epidermal growth factor receptor. In addition, LRIG1 knockdown promoted the tumorigenic potential in vitro, which was manifested as increased proliferation, invasiveness, and migration as well as increased tumor size in vivo in the xenograft model. Furthermore, LRIG1 expression was determined to be a positive prognostic biomarker for the survival of gastric cancer patients. Collectively, our findings indicate that LRIG1 expression is closely related wto gastric carcinogenesis and may play a vital role as a tumor suppressor through the modulation of epidermal growth factor receptor activity.

In vivo phototoxicity testing is important for predicting drug-induced phototoxicity in humans. Currently, there is no internationally validated in vivo test method for the photosafety evaluation of pharmaceuticals. In this study, we evaluated the phototoxicity of systemically administered drugs using SD rats. We first determined the appropriate ultraviolet A (UVA) dose using 8-methoxypsoralen, a well-known phototoxic drug. Compared to lower and higher UVA doses, we found that a UVA dose of 10 J/cm(2) allowed for the detection of phototoxic responses in both a dose- and time-dependent manner. We next performed a phototoxicity study using seven pharmaceutical drugs which included known phototoxic and non-phototoxic drugs using a UVA dose of 10 J/cm(2). In order to improve the accuracy of our assessment, we evaluated both gross skin findings as well as histopathological findings. Using gross skin findings alone resulted in an accuracy of 85.7% which could be increased to 100% accuracy when the gross skin findings were combined with histopathological findings. This study suggests that the inclusion of histopathological findings increases the accuracy of the phototoxicity evaluation of systemically administered drugs in SD rats. In conclusion, we found that for studying drug-induced phytotoxicity, a 10 J/cm(2) UVA dose serves as the optimal radiation dose, and that the inclusion of histopathological findings increases the accuracy of the phototoxicity evaluation of the drugs.

The lesion detection rate of esophagogastroduodenoscopy (EGD) varies depending on the degree of experience of the endoscopist and anatomical blind spots. This study aimed to identify gaze patterns and blind spots by analyzing the endoscopist's gaze during real-time EGD.Five endoscopists were enrolled in this study. The endoscopist's eye gaze tracked by an eye tracker was selected from the esophagogastric junction to the second portion of the duodenum without the esophagus during insertion and withdrawal, and then matched with photos. Gaze patterns were visualized as a gaze plot, blind spot detection as a heatmap, observation time (OT), fixation duration (FD), and FD-to-OT ratio.The mean OT and FD were 11.10 ± 11.14 min and 8.37 ± 9.95 min, respectively, and the FD-to-OT ratio was 72.5%. A total of 34.3% of the time was spent observing the antrum. When observing the body of the stomach, it took longer to observe the high body in the retroflexion view and the low-to-mid body in the forward view.It is necessary to minimize gaze distraction and observe the posterior wall in the retroflexion view. Our results suggest that eye-tracking techniques may be useful for future endoscopic training and education.

Some drugs cause phototoxicity in humans when exposed to light, thus there is a need for an in vivo phototoxicity test to evaluate them. However, an in vivo phototoxicity test method to evaluate this has not been established. This study aimed to establish an in vivo phototoxicity test method for transdermally administered drugs. For this, we evaluated the phototoxicity using Sprague-Dawley (SD) rats for transdermal administered drugs and we studied the appropriate UVA dose using 8-methoxypsalen, which is a well-known phototoxic drug. We found that a UVA dose of 15 J/cm2 was dose and time dependent response compared to other UVA doses. We performed the Minimum Erythema Dose (MED) test because UVB can cause skin irritation by itself and selected 0.01 J/cm2 as an appropriate dose of UVB. Using the selected UVA and UVB doses, we performed a phototoxicity study of 6 pharmaceutical drugs, which included phototoxic and non-phototoxic drugs. As a result of the phototoxicity test, 100% accuracy was obtained when compared with previous studies. In addition, we performed histopathology to confirm the new findings. We found that histopathology can be used as an additional indicator of phototoxicity test for transdermally administered drugs.

We formulate the problem of hypernym prediction as a sequence generation task, where the sequences are taxonomy paths in WordNet. Our experiments with encoder-decoder models show that training to generate taxonomy paths can improve the performance of direct hypernym prediction. As a simple but powerful model, the hypo2path model achieves state-of-the-art performance, outperforming the best benchmark by 4.11 points in hit-at-one (H@1).

Peroxidasin (PXDN) is a unique peroxidase containing extracellular matrix motifs and stabilizes collagen IV networks by forming sulfilimine crosslinks. PXDN gene knockout in Caenorhabditis elegans (C. elegans) and Drosophila results in the demise at the embryonic and larval stages. PXDN mutations lead to severe eye disorders, including microphthalmia, cataract, glaucoma, and anterior segment dysgenesis in humans and mice. To investigate how PXDN loss of function affects organ development, we generated Pxdn knockout mice by deletion of exon 1 and its 5&prime, upstream sequences of the Pxdn gene using the CRISPR/Cas9 system. Loss of both PXDN expression and collagen IV sulfilimine cross-links was detected only in the homozygous mice, which showed completely or almost closed eyelids with small eyes, having no apparent external morphological defects in other organs. In histological analysis of eye tissues, the homozygous mice had extreme defects in eye development, including no eyeballs or drastically disorganized eye structures, whereas the heterozygous mice showed normal eye structure. Visual function tests also revealed no obvious functional abnormalities in the eyes between heterozygous mice and wild-type mice. Thus, these results suggest that PXDN activity is essential in eye development, and also indicate that a single allele of Pxdn gene is sufficient for eye-structure formation and normal visual function.

미역이나 다시마와 같은 해조류는 생물의 상태로 유통될 수 없는 어려움이 있어 건조, 염장, 당장 등의 가공 처리가 필요하다. 본 실험에서는 다시마를 건조 및 전처리를 하여 해조류에 거부감을 가지고 있는 내륙지역에서도 쉽게 접근할 수 있는 스낵으로 제조하고, 맛과 씹힘성이 좋으며 비린 맛이 없어 누구나 좋아하는 스낵을 개발하고, 개발한 스낵의 물리화학적 특성을 연구하였다. 다시마 연화에 탁월한 폴리인산나트륨 용액 농도 탐색 실험에서는 0.2-0.3% 농도의 폴리인산나트륨 용액에 침지시키는 것이 다시마 연화나 맛에서 좋았고 부드러운 질감을 나타내었다. 폴리인산나트륨 용액 침지 및 굽는 처리를 달리한 다시마 스낵 제조에서는 두께가 221 mm 미만인 것은 얇은 것으로, 221 mm 이상인 것은 두꺼운 것으로 분류하여 실험을 진행하였는데, 두꺼운 다시마 스낵에서 모든 실험 결과에서 일관된 결과를 보이는 반면 얇은 다시마의 경우 일관된 결과를 보이지 않아 두꺼운 다시마로 스낵을 제조하는 것이 바람직해 보였다. 다시마 스낵은 굽는 처리를 한 것이 수분함량과 조회분 함량에서 유의적으로 높은 값을 나타내었으며, 폴리인산나트륨 용액에 침지시킨 것이 낮은 경도 값을 나타내는 것으로 보아 폴리인산나트륨 용액에 침지로 인해 다시마가 부드러워지는 것을 확인할 수 있었다. 전자현미경 촬영 결과 폴리인산나트륨 용액에 침지시키고 굽는 처리를 한 다시마 스낵이 조직이 부드러워지는 것과 좋은 질감을 가지는 것을 확인할 수 있었다. 다시마로 스낵을 제조할 때는 단백질과 회분 함량이 적절하게 포함된 중층부 다시마의 두꺼운 부분을 사용하는 것이 좋으며, 음지에서 건조시킨 다시마를 사용하는 것이 저장성이 높은 다시마 스낵을 제조하는데 바람직할 것으로 보인다. 가공 처리의 경우 폴리인산나트륨 용액에 침지 및 굽는 처리를 하여 단맛이나 매운맛의 조미를 가하여 다시마 스낵을 제조할 경우 이 물감이 없고 씹힘성이 좋으며 비린 맛이 없는 상품성이 높은 다시마 스낵을 제조할 수 있을 것으로 보인다. 해조류 섭취의 중요성에 대한 연구들이 뒷받침된다면 다시마 스낵이 남미에 수출되면 갑상선종에 대한 예방이 가능하고 수출 증대로 국가적 이익을 창출 할 수 있을 것으로 기대된다.

Background & Aims WAP 4-disulfide core domain protein 2 (WFDC2), also known as human epididymis protein 4, is a small secretory protein that is highly expressed in fibrosis and human cancers, particularly in the ovaries, lungs, and stomach. However, the role of WFDC2 in carcinogenesis is not fully understood. The present study aimed to investigate the role of WFDC2 in gastric carcinogenesis with the use of preneoplastic metaplasia models. Methods Three spasmolytic polypeptide–expressing metaplasia (SPEM) models were established in both wild-type and Wfdc2-knockout mice with DMP-777, L635, and high-dose tamoxifen, respectively. To reveal the functional role of WFDC2, we performed transcriptomic analysis with DMP-777–treated gastric corpus specimens. Results Wfdc2-knockout mice exhibited remarkable resistance against oxyntic atrophy, SPEM emergence, and accumulation of M2-type macrophages in all 3 SPEM models. Transcriptomic analysis revealed that Wfdc2-knockout prevented the up-regulation of interleukin-33 (IL33) expression in the injured mucosal region of SPEM models. Notably, supplementation of recombinant WFDC2 induced IL33 production and M2 macrophage polarization, and ultimately promoted SPEM development. Moreover, long-term treatment with recombinant WFDC2 was able to induce SPEM development. Conclusions WFDC2 expressed in response to gastric injury promotes SPEM through the up-regulation of IL33 expression. These findings provide novel insights into the role of WFDC2 in gastric carcinogenesis.

Drug-induced liver injury (DILI) is the serious and fatal drug-associated adverse effect, but its incidence is very low and individual variation in severity is substantial. Acetaminophen (APAP)-induced liver injury accounts for >50% of reported DILI cases but little is known for the cause of individual variations in the severity. Intrinsic genetic variation is considered a key element but the identity of the genes was not well-established. Here, pre-biopsy method and microarray technique was applied to uncover the key genes for APAP-induced liver injury in mice, and a cause and effect experiment employing quantitative real-time PCR was conducted to confirm the correlation between the uncovered genes and APAP-induced hepatotoxicity. We identified the innately and differentially expressed genes of mice susceptible to APAP-induced hepatotoxicity in the pre-biopsied liver tissue before APAP treatment through microarray analysis of the global gene expression profiles (Affymetrix GeneChip® Mouse Gene 1.0 ST for 28,853 genes). Expression of 16 genes including Gdap10, Lpl, Gabra3 and Ccrn4l were significantly different (t-test: FDR

Peroxidasin (PXDN) is a unique peroxidase containing extracellular matrix motifs and stabilizes collagen IV networks by forming sulfilimine crosslinks. PXDN gene knockout in Caenorhabditis elegans (C. elegans) and Drosophila results in the demise at the embryonic and larval stages. PXDN mutations lead to severe eye disorders, including microphthalmia, cataract, glaucoma, and anterior segment dysgenesis in humans and mice. To investigate how PXDN loss of function affects organ development, we generated Pxdn knockout mice by deletion of exon 1 and its 5′ upstream sequences of the Pxdn gene using the CRISPR/Cas9 system. Loss of both PXDN expression and collagen IV sulfilimine cross-links was detected only in the homozygous mice, which showed completely or almost closed eyelids with small eyes, having no apparent external morphological defects in other organs. In histological analysis of eye tissues, the homozygous mice had extreme defects in eye development, including no eyeballs or drastically disorganized eye structures, whereas the heterozygous mice showed normal eye structure. Visual function tests also revealed no obvious functional abnormalities in the eyes between heterozygous mice and wild-type mice. Thus, these results suggest that PXDN activity is essential in eye development, and also indicate that a single allele of Pxdn gene is sufficient for eye-structure formation and normal visual function.

p16Ink4a/CDKN2A is a tumor suppressor that critically regulates the cell cycle. Indeed, p16Ink4a deficiency promotes tumor formation in various tissues. We now report that p16Ink4a deficiency in female mice, but not male mice, induces leanness especially in old age, as indicated by lower body weight and smaller white adipose tissue, although other major organs are unaffected. Unexpectedly, the integrity, number, and sizes of adipocytes in white adipose tissue were unaffected, as was macrophage infiltration. Hence, hypermobility appeared to be accountable for the phenotype, since food consumption was not altered. Histological analysis of the cerebellum and deep cerebellar nuclei, a vital sensorimotor control center, revealed increased proliferation of neuronal cells and improved cerebellum integrity. Expression of estrogen receptor β (ERβ) and PCNA also increased in deep cerebellar nuclei, implying crosstalk between p16Ink4a and ERβ. Furthermore, p16Ink4a deficiency expands LC3B+ cells and GFAP+ astrocytes in response to estrogen. Collectively, the data suggest that loss of p16INK4a induces sexually dimorphic leanness in female mice, which appears to be due to protection against cerebellar senescence by promoting neuronal proliferation and homeostasis via ERβ.

Rab25 can function as both a tumor suppressor and a tumor promoter across different tissues. This study sought to clarify the role of Rab25 as a tumor suppressor in skin squamous cell carcinoma (SCC). Rab25 loss was closely associated with neoplastic transition in both humans and mice. Rab25 loss was well correlated with increased cell proliferation and poor differentiation in human SCC. While Rab25 knockout (KO) in mice did not induce spontaneous tumor formation, it did significantly accelerate tumor generation and promote malignant transformation in a mouse two-stage skin carcinogenesis model. Xenografting of a Rab25-deficient human keratinocyte cell line, HaCaT, also elicited neoplastic transformation. Notably, Rab25 deficiency led to dysregulation of integrins β1, β4, and α6, which matched well with increased epidermal proliferation and impaired desmosome-tight junction formation. Rab25 deficiency induced impairment of integrin recycling, leading to the improper expression of integrins. In line with this, significant attenuation of integrin β1, β4, and α6 expression was identified in human SCCs where Rab25 was deficient. Collectively, these results suggest that loss of Rab25 promotes the development and neoplastic transition of SCC through dysregulation of integrin trafficking. © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.