Peritoneal Washing Cytology Positivity in Gastric Cancer: Role of Lymph Node Metastasis as a Risk Factor.

PURPOSE: Peritoneal washing cytology (PWC) is a widely used diagnostic tool for detecting peritoneal metastasis of advanced gastric cancer. However, the prognosis of patients with positive PWC remains poor even after gastrectomy, and treatments vary among institutions and eras. In this study, we identified the clinical factors that can help predict cytology-positive (CY(+)) gastric cancer. MATERIALS AND METHODS: We retrospectively reviewed the national data of patients with gastric cancer from 2019, as provided by the Information Committee of the Korean Gastric Cancer Association. Of the 13,447 patients with gastric cancer, 3,672 underwent PWC. Based on cytology results, we analyzed the clinicopathological characteristics and assessed the possibility of CY(+) outcomes in relation to T and N stages. RESULTS: Of the 3,270 patients who underwent PWC without preoperative chemotherapy, 325 were CY(+), whereas 2,945 were negative. CY(+) was more commonly observed in patients with Borrmann type IV gastric cancer, an undifferentiated histological type, and advanced pathological stages. Multivariate analysis revealed Borrmann type IV (odds ratio [OR], 1.821), tumor invasion to T3-4 (OR, 2.041), and lymph node metastasis (OR, 3.155) as independent predictors of CY(+). Furthermore, for circular tumor location, the N stage emerged as a significant risk factor for CY(+), particularly when the tumor was located on the posterior wall (PW) side. CONCLUSIONS: Lymph node metastasis significantly affects CY(+) outcomes, particularly when the tumor is located on the PW side. Therefore, PWC should be considered not only in suspected serosal exposure cases but also in cases of lymph node metastasis.

Regeneration of Non-Alcoholic Fatty Liver Cells Using Chimeric FGF21/HGFR: A Novel Therapeutic Approach.

Non-alcoholic fatty liver disease (NAFLD) has emerged as a significant liver ailment attributed to factors like obesity and diabetes. While ongoing research explores treatments for NAFLD, further investigation is imperative to address this escalating health concern. NAFLD manifests as hepatic steatosis, precipitating insulin resistance and metabolic syndrome. This study aims to validate the regenerative potential of chimeric fibroblast growth factor 21 (FGF21) and Hepatocyte Growth Factor Receptor (HGFR) in NAFLD-afflicted liver cells. AML12, a murine hepatocyte cell line, was utilized to gauge the regenerative effects of chimeric FGF21/HGFR expression. Polysaccharide accumulation was affirmed through Periodic acid-Schiff (PAS) staining, while LDL uptake was microscopically observed with labeled LDL. The expression of FGF21/HGFR and NAFLD markers was analyzed by mRNA analysis with RT-PCR, which showed a decreased expression in acetyl-CoA carboxylase 1 (ACC1) and sterol regulatory element binding protein (SREBP) cleavage-activating protein (SCAP) with increased expression of hepatocellular growth factor (HGF), hepatocellular nuclear factor 4 alpha (HNF4A), and albumin (ALB). These findings affirm the hepato-regenerative properties of chimeric FGF21/HGFR within AML12 cells, opening novel avenues for therapeutic exploration in NAFLD.

Mechanistic Investigation, Wavelength-Dependent Reactivity, and Expanded Reactivity of N-Aryl Azacycle Photomediated Ring Contractions.

Under mild blue-light irradiation, α-acylated saturated heterocycles undergo a photomediated one-atom ring contraction that extrudes a heteroatom from the cyclic core. However, for nitrogenous heterocycles, this powerful skeletal edit has been limited to substrates bearing electron-withdrawing substituents on nitrogen. Moreover, the mechanism and wavelength-dependent efficiency of this transformation have remained unclear. In this work, we increased the electron richness of nitrogen in saturated azacycles to improve light absorption and strengthen critical intramolecular hydrogen bonding while enabling the direct installation of the photoreactive handle. As a result, a broadly expanded substrate scope, including underexplored electron-rich substrates and previously unsuccessful heterocycles, has now been achieved. The significantly improved yields and diastereoselectivities have facilitated reaction rate, kinetic isotope effect (KIE), and quenching studies, in addition to the determination of quantum yields. Guided by these studies, we propose a revised ET/PT mechanism for the ring contraction, which is additionally corroborated by computational characterization of the lowest-energy excited states of α-acylated substrates through time-dependent DFT. The efficiency of the ring contraction at wavelengths longer than those strongly absorbed by the substrates was investigated through wavelength-dependent rate measurements, which revealed a red shift of the photochemical action plot relative to substrate absorbance. The elucidated mechanistic and photophysical details effectively rationalize empirical observations, including additive effects, that were previously poorly understood. Our findings not only demonstrate enhanced synthetic utility of the photomediated ring contraction and shed light on mechanistic details but may also offer valuable guidance for understanding wavelength-dependent reactivity for related photochemical systems.

The Prediction Model of Non-Suicidal Self-Injury in Psychiatric Patients Using Decision Tree Analysis.

PURPOSE: The prevalence rate of non-suicidal self-injury (NSSI) in the clinical population is higher than that in the community sample, necessitating the need to investigate the predicting factors of NSSI in this group. The present study aimed to develop a prediction model of NSSI among psychiatric patients in Korea. MATERIALS AND METHODS: Decision tree analysis was conducted on a sample of 224 psychiatric patients. Emotion regulation strategies (rumination, cognitive reappraisal, and expressive suppression), impulsivity, problematic alcohol use, working memory, depressive mood, and gender were included in the model as predictors of NSSI. RESULTS: Results indicated that rumination, problematic alcohol use, and working memory predicted lifetime NSSI engagement among psychiatric patients. The best predictor of lifetime NSSI engagement was rumination. Specifically, when the level of rumination was high, the level of working memory was lower, and the risk of NSSI was higher. In the case of low levels of rumination, the higher the level of problematic alcohol use, the higher the risk of NSSI. The highest prevalence of lifetime NSSI engagement was found in a subgroup of patients with high levels of rumination and low levels of working memory. CONCLUSION: The major contribution of this study is finding a combination of factors to predict the high-risk group of NSSI among psychiatric patients in Korea. This study provides evidence on the effect of rumination, working memory, and problematic alcohol use on NSSI. It is suggested that clinicians and researchers should pay more attention to emotion regulation and related vulnerabilities in preventing and treating NSSI.

Depression and posttraumatic stress disorder in adolescents with nonsuicidal self-injury: comparisons of the psychological correlates and suicidal presentations across diagnostic subgroups.

BACKGROUND: Nonsuicidal self-injury (NSSI) combined with suicide ideation increases the risk of suicidal behaviors. Depression and posttraumatic stress disorder (PTSD) are comorbidities of NSSI compounding this relationship. The present study compared diagnostic subgroups of NSSI based on current depression and PTSD on psychological correlates (i.e., vulnerabilities and impairment) and suicidal presentations (i.e., suicidal cognitions and behaviors) in a psychiatric sample of adolescents. METHODS: Eighty-seven adolescents meeting DSM-5 criteria for NSSI and 104 age-range-matched nonclinical controls (NC) participated. Participants completed self-report measures on psychological vulnerabilities and impairment (e.g., emotion regulation difficulties, negative cognitions). Adolescents with NSSI also completed clinical interviews on psychiatric diagnoses and a recent self-injurious behavior (SIB). Scores on the psychological correlates of NSSI were compared between adolescents with NSSI and NC, and across three diagnostic subgroups of NSSI (A: NSSI+/depression-/PTSD-, n = 14; B: NSSI+/depression+/PTSD-, n = 57; C: NSSI+/depression+/PTSD+, n = 14). Differences between NSSI diagnostic subgroups were tested on the motives for SIB and accompanying suicidal presentations (e.g., desire, intent, motive, lethality). RESULTS: Common comorbidities of NSSI included depression, panic disorder, generalized anxiety disorder, and PTSD. The NSSI subgroup classification was significantly associated with panic disorder, which was controlled for in the subsequent group comparisons. Overall, adolescents who engage in NSSI with vs. without depression reported more psychological vulnerabilities and impairment and a greater degree of suicidal thoughts/desire in SIB (i.e., groups B, C >A), which remained significant after controlling for panic disorder. An increased odds of the suicidal motive for SIB was found in adolescents with all three conditions (i.e., group C: NSSI+/depression+/PTSD+) compared to those with NSSI but neither depression nor PTSD (i.e., group A: NSSI+/depression-/PTSD-); however, this was not significant after controlling for panic disorder. CONCLUSIONS: Psychological underpinnings of adolescent NSSI in clinical contexts may be largely associated with concurrent depression. Suicidal motives in adolescents who engage in NSSI in the presence of depression and PTSD may be confounded by the co-occurrence of panic disorder. This study warrants the importance of attending to the comorbid depression with NSSI in adolescents as it is related to an increase in suicidal desire accompanying SIB.

Misinformation, Risk Perceptions, and Intention to Seek Information About Masks: The Moderating Roles of Gender and Reflective Judgment.

The current study has three main purposes: to examine 1) the impact of theory-driven corrective messages using individual vs. collective frames on information-seeking intention 2) the mediating role of risk perceptions and 3) the moderating role of reflection and gender. Our findings from a randomized experimental study and Hayes' moderated, moderated mediation model show collective frames were associated with high-risk perceptions among women, which in turn led to higher information seeking intention. The second moderator reveals that people who scored higher on reflection were more willing to seek information. Our findings have critical implications for misinformation research by demonstrating the importance of theoretically driven messages in understanding misperceptions as well as people's information seeking behavior.

Multimodal Golden DNA Superstructures (GDSs) for Highly Efficient Photothermal Immunotherapy.

DNA-templated metallization has emerged as an efficient strategy for creating nanoscale-metal DNA hybrid structures with a desirable conformation and function. Despite the potential of DNA-metal hybrids, their use as combinatory therapeutic agents has rarely been examined. Herein, we present a simple approach for fabricating a multipurpose DNA superstructure that serves as an efficient photoimmunotherapy agent. Specifically, we adsorb and locally concentrate Au ions onto DNA superstructures through induced local reduction, resulting in the formation of Au nanoclusters. The mechanical and optical properties of these metallic nanoclusters can be rationally controlled by their conformations and metal ions. The resulting golden DNA superstructures (GDSs) exhibit significant photothermal effects that induce cancer cell apoptosis. When sequence-specific immunostimulatory effects of DNA are combined, GDSs provide a synergistic effect to eradicate cancer and inhibit metastasis, demonstrating potential as a combinatory therapeutic agent for tumor treatment. Altogether, the DNA superstructure-templated metal casting system offers promising materials for future biomedical applications.

Escherichia coli adhesion protein FimH exacerbates colitis via CD11b+CD103- dendritic cell activation.

Introduction: Immune stimulators are used to improve vaccine efficiency; however, they are accompanied by various side effects. In previous studies, we reported that the Escherichia coli adhesion protein, FimH, induces immune activity; however, we did not examine any side effects in colon inflammation. Methods: FimH was administered orally or intraperitoneally (i.p.) to mice with dextran sulfate sodium (DSS)-induced colitis, and changes in symptoms were observed. Immune cells infiltrated into the colon after the induction of colon inflammation were analyzed using a flow cytometer. Changes in Th1 and Th17 cells that induce colitis were analyzed. Further, mesenteric lymph node (mLN) dendritic cells (DCs) activated by FimH were identified and isolated to examine their ability to induce T-cell immunity. Results: FimH oral and i.p. administration in C57BL/6 mice did not induce inflammation in the colon; however, DSS-induced colitis was exacerbated by oral and i.p. FimH administration. FimH treatment increased immune cell infiltration in the colon compared to that in DSS colitis. Th1 and Th17 cells, which are directly related to colitis, were increased in the colon by FimH; however, FimH did not directly affect the differentiation of these T cells. FimH upregulated the CD11b+CD103- DC activity in the mLNs, which produced the signature cytokines required for Th1 and Th17. In addition, isolated CD11b+CD103- DCs, after stimulation with FimH, directly induced Th1 and Th17 differentiation in a co-culture of CD4 T cells. Conclusion: This study demonstrated the side effects of FimH and indicated that the use of FimH can aggravate the disease in patients with colitis.

Indocyanine Green (ICG) in Robotic Gastrectomy: A Retrospective Review of Lymphadenectomy Outcomes for Gastric Cancer.

Radical gastrectomy is essential for gastric cancer treatment. While guidelines advise dissecting at least 16 lymph nodes, some research suggests over 30 nodes might be beneficial. This study assessed ICG-guided robotic gastrectomy's effectiveness in thorough lymph node dissection. We analyzed data from 393 stage II or III gastric cancer patients treated at Seoul St. Mary's Hospital from 2016-2022. Patients were categorized into conventional laparoscopy (G1, n = 288), ICG-guided laparoscopy (G2, n = 61), and ICG-guided robotic surgery (G3, n = 44). Among 391 patients, 308 (78.4%) achieved proper lymphadenectomy. The ICG-robotic group (G3) showed the highest success rate at 90.9%. ICG-guided robotic surgery was a significant predictor for achieving proper lymphadenectomy, with an odds ratio of 3.151. In conclusion, ICG-robotic gastrectomy improves lymphadenectomy outcomes in selected gastric cancer cases, indicating a promising surgical approach for the future.

Interconverting mirror-image molecules.

A light-driven multitasking catalyst enhances chirality in molecular mixtures.

Linking Clinic With Classroom in Intensive Focused Preservice Education on Augmentative and Alternative Communication.

PURPOSE: This article reports a pilot study that combined clinical training and academic instruction in a graduate-level augmentative and alternative communication (AAC) course. The authors aim to (a) provide a detailed description of the AAC course and (b) present preliminary data regarding the graduate students' perception on the AAC course and their own competencies in AAC. METHOD: Forty-three graduate students completed an intensive focused course that included AAC fieldwork (i.e., direct clinical service and caregiver training) as well as academic content. In delivering the clinical and academic content, the course instructor followed the principles of problem-based learning. During their final semester in the graduate program, the students completed a survey regarding the AAC course and their self-efficacy in AAC services. RESULTS: Thirty-eight among the 43 students perceived that the AAC fieldwork, embedded into the AAC course, made them feel competent or strongly competent. The entire 43 respondents listed the AAC fieldwork as the component that they liked in the AAC course. When students were asked about their self-efficacy in AAC services at three different time points (i.e., before taking the AAC course, after taking the AAC course, and at the time of the survey), their ratings were significantly higher for after taking the AAC course and at the time of the survey, compared to before taking the course. CONCLUSION: This study suggests the significance of compulsory fieldwork embedded in the AAC training as evidenced by the graduate students' subjective perception of competence and preparedness in AAC services following the AAC course.

Feasibility and Potential of Reduced Port Surgery for Total Gastrectomy With Overlap Esophagojejunal Anastomosis Method.

PURPOSE: Reduced port surgery (RPS) for gastric cancer has been frequently reported in distal gastrectomies but rarely in total gastrectomies. This study aimed to determine the feasibility of 3-port totally laparoscopic total gastrectomy (TLTG) with overlapping esophagojejunal (EJ) anastomosis. MATERIALS AND METHODS: A total of 81 patients who underwent curative TLTG for gastric cancer (36 and 45 patients with 3-port and 5-port TLTG, respectively) were evaluated. All 3-port TLTG procedures were performed with the same method as 5-port TLTG, including EJ anastomosis with the intracorporeal overlap method using a linear stapler, except for the number of ports and assistants. Short-term outcomes, including the number of lymph nodes (LNs) harvested by station and postoperative complications, were analyzed retrospectively. RESULTS: Clinical characteristics were not significantly different among the groups, except that the 3-port TLTG group was younger and had a lower rate of pulmonary comorbidity. There were no cases of open conversion or additional port placement. All operative details and the number of harvested LNs did not differ between the groups, but the rate of suprapancreatic LN harvest was higher in the 3-port TLTG group. No significant differences were observed in the overall complication rates between the 2 groups. CONCLUSIONS: Three-port TLTG with overlapping EJ anastomoses using a linear stapler is a feasible RPS procedure for total gastrectomy to treat gastric cancer.

Immunosuppressive nanoparticles containing recombinant PD-L1 and methotrexate alleviate multi-organ inflammation.

Multi-organ inflammatory diseases are one of the most serious autoimmune diseases worldwide. The regulation of immune responses by immune checkpoint proteins influences the development and treatment of cancer and autoimmune diseases. In this study, recombinant murine PD-L1 (rmPD-L1) was used for controlling T cell immunity to treat multi-organ inflammation. To enhance the immunosuppressive effect, we incorporated methotrexate, an anti-inflammatory drug, into hybrid nanoparticles (HNPs) and decorated the surface of HNPs with rmPD-L1 to produce immunosuppressive HNPs (IsHNPs). IsHNP treatment effectively targeted PD-1-expressing CD4 and CD8 T cells in the splenocytes; additionally, it promoted the production of Foxp3-expressing regulatory T cells, which suppressed the differentiation of helper T cells. IsHNP treatment also inhibited anti-CD3 antibody-mediated activation of CD4 and CD8 T cells in mice in vivo. This treatment protected mice from multi-organ inflammation induced by the adoptive transfer of naïve T cells to recombination-activating gene 1 knockout mice. The results of this study imply the therapeutic potential of IsHNPs in the treatment of multi-organ inflammation and other inflammatory diseases.

A Story is Better Told With Collective Interests: An Experimental Examination of Misinformation Correction During the COVID-19 Pandemic.

PURPOSE: To examine strategies that help motivate social correction behaviors to combat COVID-19-related health misinformation on social media. DESIGN: 2 (message types: narrative vs statistics) x 2 (social frames: individual vs collective) between-subjects experiment. SETTING: Qualtrics-based online experiment via Lucid. SUBJECTS: The final sample consisted of 450 participants (Mage = 45.31). MEASURES: Manipulation check, discussion and correction intentions, and need for cognition (NFC). ANALYSIS: ANCOVA and PROCESS model 3 were used to analyze the data. RESULTS: Significant interaction effects emerged between message types and social frames on discussion intention, F (1, 442) = 5.26, P = .022, and correction intention, F (1, 442) = 4.85, P = .028. Collectively framed narrative correction (Mdiscussion = 3.15, Mcorrection = 3.17) was more effective than individually framed narrative correction (Mdiscussion = 2.73, Mcorrection = 2.77). Individually framed statistical correction (Mdiscussion = 3.10, Mcorrection = 2.95) was more persuasive than collectively framed statistical correction (Mdiscussion = 2.89, Mcorrection = 2.69). The interaction effects were more evident for people low on NFC, P = .031. CONCLUSION: In motivating social correction behaviors, a story is better told with an emphasis on collective interests, and numbers are better presented with personal gains and losses. Future interventions should identify the target audience based on the level of NFC.

Predictive model for long-term weight recovery after gastrectomy for gastric cancer: an introduction to a web calculator.

BACKGROUND: Weight changes after gastrectomy affect not only quality of life but also prognosis and survival. However, it remains challenging to predict the weight changes of individual patients. Using clinicopathological variables, we built a user-friendly tool to predict weight change after curative gastrectomy for gastric cancer. METHODS: The clinical data of 984 patients who underwent curative gastrectomy between 2009 and 2013 were retrospectively reviewed and analyzed. Multivariate logistic regression was performed to identify variables predictive of postoperative weight change. A nomogram was developed and verified via bootstrap resampling. RESULTS: Age, sex, performance status, body mass index, extent of resection, pathological stage, and postoperative weight change significantly influenced postoperative weight recovery. Postoperative levels of hemoglobin, albumin, ferritin and total iron-binding capacity were significant covariates. The nomogram performed well (concordance index = 0.637); calibration curves indicated appropriate levels of agreement. We developed an online weight prediction calculator based on the nomogram ( http://gc-weightchange.com/en/front/ ). CONCLUSIONS: The novel, Web-calculator based on the predictive model allows surgeons to explore patient weight patterns quickly. The model identifies patients at high risk for weight loss after gastrectomy; such patients require multidisciplinary medical support.

Enhancement of Muscle Shortening Torque Preloaded with Muscle Lengthening is Joint-Specific.

Our cross-sectional study aimed to investigate joint specificity of concentric muscle torque enhancement after a maximum eccentric contraction for the knee versus ankle joints across two different movement velocities (120°/s and 180°/s). After a familiarization session, 22 healthy young adults randomly performed concentric (CONC) and maximum eccentric preloaded concentric (EccCONC) muscle strength tests of the knee extensors and ankle plantar flexors of the non-dominant leg on an isokinetic strength testing device. We calculated the ratio between EccCONC and CONC (EccCONC/CONC) for all the conditions as the marker of concentric muscle torque enhancement. Separate two-way (joints x velocity) within repeated measures ANOVAs were used to determine joint-specific torque differences at 120°/s and 180°/s. CONC and EccCONC were greater for the knee extensors versus ankle plantar flexors at 120°/s and 180°/s (32.86%-102%; p < 0.001 for both); however, EccCONC/CONC was greater for the ankle plantar flexors than knee extensors at 120°/s (52.4%; p < 0.001) and 180°/s (41.9%; p < 0.001). There was a trend of greater EccCONC/CONC for the knee extensors at 180°/s than 120°/s (6.6%; p = 0.07). Our results show that greater concentric muscle torque enhancement after a maximal eccentric contraction occurs for the ankle plantar flexors versus knee extensors. Whether the joint- specificity of concentric muscle torque enhancement after a maximal eccentric contraction differentially affects sports performance is unknown. Our data provide a reference framework to investigate joint-specific concentric muscle torque enhancement for general and clinical athletic populations.

Investigation of the Subtypes of Nonsuicidal Self-Injury Based on the Forms of Self-Harm Behavior: Examining Validity and Utility via Latent Class Analysis and Ecological Momentary Assessment.

BACKGROUND: This study aimed to empirically derive and validate subtypes of nonsuicidal self-injury (NSSI) based on the forms of self-harm behavior. METHODS: Sixty young adults who exhibited repetitive NSSI completed a clinical interview and baseline measures, followed by a two-week ecological momentary assessment (EMA). A latent class analysis was administered to identify NSSI subtypes based on the forms of self-harm behavior. The subtypes were then compared to baseline clinical and EMA variables, including emotions and urges to self-harm. RESULTS: The best-fitting model supported two subtypes: 1) substance abuse and suicide attempt subtype and 2) cutting and scratching subtype. The substance abuse and suicide attempt subtype reported a higher rate of engaging in lifetime suicide plans and suicide attempts and a higher number of lifetime suicide attempts. They also showed significantly higher severity of self-harm behavior, borderline personality traits, anger, posttraumatic symptoms, and difficulties in emotion regulation when compared to the cutting and scratching subtype. However, there was no inter-subtype difference in self-esteem. In the EMA data, anger toward others, feeling of rejection, loneliness, and helplessness were significantly high in the substance abuse and suicide attempt subtype. The variability of anger toward others was also higher in this subtype compared to the cutting and scratching subtype. Finally, in the two-week research period, the substance abuse and suicide attempt group showed a higher rate of reported urges to self-harm with or without suicidal intent. CONCLUSION: Findings support the validity of the subtypes based on the forms of self-harm behavior, suggesting the clinical utility of addressing heterogeneity within individuals exhibiting self-harm for assessment and treatment.

Lipid Nanocarrier-Based Drug Delivery Systems: Therapeutic Advances in the Treatment of Lung Cancer.

Although various treatments are currently being developed, lung cancer still has a very high mortality rate. Moreover, while various strategies for the diagnosis and treatment of lung cancer are being used in clinical settings, in many cases, lung cancer does not respond to treatment and presents reducing survival rates. Cancer nanotechnology, also known as nanotechnology in cancer, is a relatively new topic of study that brings together scientists from a variety of fields, including chemistry, biology, engineering, and medicine. The use of lipid-based nanocarriers to aid drug distribution has already had a significant impact in several scientific fields. Lipid-based nanocarriers have been demonstrated to help stabilize therapeutic compounds, overcome barriers to cellular and tissue absorption, and improve in vivo drug delivery to specific target areas. For this reason, lipid-based nanocarriers are being actively researched and used for lung cancer treatment and vaccine development. This review discusses the improvements in drug delivery achieved with lipid-based nanocarriers, the obstacles that still exist with in vivo applications, and the current clinical and experimental applications of lipid-based nanocarriers in lung cancer treatment and management.

Pyropia yezoensis-derived porphyran attenuates acute and chronic colitis by suppressing dendritic cells.

Porphyran is known to inhibit immune cell function. Previously, porphyran was shown to prevent lipopolysaccharide-induced sepsis in mice. However, studies on the inhibitory effects of porphyran during colitis are currently lacking. In this study, we evaluated the effects of Pyropia yezoensis-derived porphyran on dextran sodium sulfate (DSS)-induced acute and chronic colitis. The oral or intraperitoneal administration of porphyran inhibited the progression of DSS-induced colitis in mice, with the former also preventing immune cell infiltration in the colon. The levels of intracellular interferon-γ and interleukin-17 in T cells decreased when porphyran was administered orally. Porphyran inhibited T cell activation by suppressing dendritic cells (DCs) and macrophages. Porphyran prevented pathogen-associated molecular pattern and damage-associated molecular pattern-dependent DC and macrophage activation. Finally, porphyran attenuated chronic colitis caused via the long-term administration of DSS. These findings indicate that the oral administration of porphyran can inhibit DSS-induced colitis by suppressing DC and macrophage activation.

Modulation of histone H3K4 dimethylation by spermidine ameliorates motor neuron survival and neuropathology in a mouse model of ALS.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by progressive paralysis due to motor neuron degeneration. It has been proposed that epigenetic modification and transcriptional dysregulation may contribute to motor neuron death. In this study, we investigate the basis for therapeutic approaches to target lysine-specific histone demethylase 1 (LSD1) and elucidate the mechanistic role of LSD1-histone H3K4 signaling pathway in ALS pathogenesis. METHODS: In order to examine the role of spermidine (SD), we administered SD to an animal model of ALS (G93A) and performed neuropathological analysis, body weight, and survival evaluation. RESULTS: Herein, we found that LSD1 activity is increased while levels of H3K4me2, a substrate of LSD1, is decreased in cellular and animal models of ALS. SD administration modulated the LSD1 activity and restored H3K4me2 levels in ChAT-positive motor neurons in the lumbar spinal cord of ALS mice. SD prevented cellular damage by improving the number and size of motor neurons in ALS mice. SD administration also reduced GFAP-positive astrogliogenesis in the white and gray matter of the lumbar spinal cord, improving the neuropathology of ALS mice. Moreover, SD administration improved the rotarod performance and gait analysis of ALS mice. Finally, SD administration delayed disease onset and prolonged the lifespan of ALS (G93A) transgenic mice. CONCLUSION: Together, modulating epigenetic targets such as LSD1 by small compounds may be a useful therapeutic strategy for treating ALS.