Successful interventional occlusion of muscular ventricular septal defect in a dog.

Ventricular septal defect (VSD) is a rare congenital heart disease in dogs. Hemodynamically important interventricular defects must be closed to improve the prognosis. This case report describes successful interventional transcatheter closure of a muscular VSD in a young Maltese and poodle mixed-breed dog with a large muscular interventricular defect (~5 mm in diameter) with a high rate of left-to-right shunt flow. The VSD was closed with a customized Amplatzer-type VSD occluder via a percutaneous transvenous (jugular) approach. We concluded that interventional occlusion of a muscular VSD with an Amplatzer-type occluder is a viable treatment option for dogs. A regular follow-up study for this dog is ongoing and has not detected complications. Key clinical message: Interventional occlusion of a muscular VSD with an Amplatzer-type occluder is a viable treatment option for dogs.

Occlusion interventionnelle réussie d'une communication interventriculaire musculaire chez un chien. La communication interventriculaire (VSD) est une maladie cardiaque congénitale rare chez le chien. Les anomalies interventriculaires hémodynamiquement importantes doivent être fermées pour améliorer le pronostic. Ce rapport de cas décrit la fermeture interventionnelle réussie par cathéter d'un VSD musculaire chez un jeune chien de race mixte (maltais et caniche) présentant un défaut interventriculaire musculaire important (~5 mm de diamètre) avec un débit de shunt élevé de gauche à droite. Le VSD a été fermé avec un obturateur VSD personnalisé de type Amplatzer via une approche trans-veineuse percutanée (jugulaire). Nous avons conclu que l'occlusion interventionnelle d'un VSD musculaire avec un obturateur de type Amplatzer est une option de traitement viable pour les chiens. Une étude de suivi régulière de ce chien est en cours et aucune complication n'a été détectée.Message clinique clé :L'occlusion interventionnelle d'un VSD musculaire avec un obturateur de type Amplatzer est une option de traitement viable pour les chiens.(Traduit par Dr Serge Messier).

Acupuncture for the treatment of trigeminal neuralgia: A systematic review and meta-analysis.

BACKGROUND AND PURPOSE: Few systematic reviews have examined the effects of acupuncture on trigeminal neuralgia. This review aims to provide up-to-date evidence on the efficacy of acupuncture for managing pain in patients with trigeminal neuralgia. METHODS: Eleven databases were searched from inception until November 2022 for relevant articles Two researchers independently conducted study selection, data extraction, and evaluation. The present review solely targeted randomized controlled trials (RCTs). The Cochrane risk of bias assessment tool 2.0 was employed to assess the risk of bias. Data were compiled using RevMan 5.4.1 software, and the quality of the evidence was evaluated using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach. RESULTS: Thirty studies involving 2295 patients were included in this review. Compared with carbamazepine, acupuncture led to improvements in pain scores (15 RCTs, mean difference (MD) - 1.40, 95% confidence interval (CI)-1.82 to -0.98 [95% prediction interval, -3.137,0.343], p < 0.00001, low certainty of evidence (CoE)), response rates (29 RCTs, risk ratio (RR) 1.20, 95% CI 1.15 to 1.25 [95% prediction interval, 1.067, 1.346], p < 0.00001, low CoE), frequency of pain attacks (2 RCTs, MD -2.53, 95% CI -4.11 to -0.96, P = 0.002, low CoE), and adverse effects (13 RCTs, risk difference (RD) -0.15, 95% CI -0.19 to -0.11 [95% prediction interval, -0.193, -0.108], P < 0.00001, very low CoE). CONCLUSION: Although the quality of evidence is low, compared with carbamazepine, acupuncture may improve trigeminal neuralgia-related pain. Further rigorously designed studies are warranted to confirm the effects of acupuncture on patients with trigeminal neuralgia.

Temsirolimus Enhances Anti-Cancer Immunity by Inducing Autophagy-Mediated Degradation of the Secretion of Small Extracellular Vesicle PD-L1.

Tumor-derived small extracellular vesicle (sEV) programmed death-ligand 1 (PD-L1) contributes to the low reactivity of cells to immune checkpoint blockade therapy (ICBT), because sEV PD-L1 binds to programmed death 1 (PD-1) in immune cells. However, there are no commercially available anti-cancer drugs that activate immune cells by inhibiting tumor-derived sEV PD-L1 secretion and cellular PD-L1. Here, we aimed to investigate if temsirolimus (TEM) inhibits both sEV PD-L1 and cellular PD-L1 levels in MDA-MB-231 cells. In cancer cell autophagy activated by TEM, multivesicular bodies (MVBs) associated with the secretion of sEV are degraded through colocalization with autophagosomes or lysosomes. TEM promotes CD8+ T cell-mediated anti-cancer immunity in co-cultures of CD8+ T cells and tumor cells. Furthermore, the combination therapy of TEM and anti-PD-L1 antibodies enhanced anti-cancer immunity by increasing both the number and activity of CD4+ and CD8+ T cells in the tumor and draining lymph nodes (DLNs) of breast cancer-bearing immunocompetent mice. In contrast, the anti-cancer effect of the combination therapy with TEM and anti-PD-L1 antibodies was reversed by the injection of exogenous sEV PD-L1. These findings suggest that TEM, previously known as a targeted anti-cancer drug, can overcome the low reactivity of ICBT by inhibiting sEV PD-L1 and cellular PD-L1 levels.

Electroacupuncture for the treatment of frozen shoulder: A systematic review and meta-analysis.

Background: Electroacupuncture (EA) has reportedly been successful in controlling pain, but there have been no systematic reviews examining the impact of EA on patients with frozen shoulder (FS). The purpose of this review is to provide evidence on the safety and efficacy of EA for pain management in patients with FS. Methods: We searched 11 databases from their inception: EMBASE, the Cochrane Library, PubMed, AMED, one Chinese medical database, and six Korean medical databases. Two researchers independently performed the study selection, data extraction, and assessment. Bias-related risk was evaluated using the Cochrane risk-of-bias assessment tool. Results: This review included thirteen studies involving 936 patients. The EA group exhibited improvements in FS pain (MD -1.11, 95% CI -1.61 to -0.61, p < 0.0001, I 2 = 97%), function (SMD 2.02, 95% CI 0.36-3.69, p < 0.00001, I 2 = 97%), and response rates (RR 1.16, 95% CI 1.07-1.25; p = 0.0002; I 2 = 0%) over the manual acupuncture (MA) group. As an adjunct treatment, EA improved FS pain (SMD -1.12, 95% CI -1.52 to -0.71, P < 0.00001, I 2 = 0) compared to the control treatments. No adverse effects were reported. Conclusion: EA is reported to improve FS pain and function compared with control treatments. Additionally, EA can be used as an adjunct therapy for FS pain. EA could emerge as a potent intervention against FS. Systematic review registration: [http://www.crd.york.ac.uk/PROSPERO/display_record.php?ID=CRD42021247090], identifier [CRD42021247090].

Preclinical assessment and randomized Phase I study of CT-P63, a broadly neutralizing antibody targeting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in significant morbidity and mortality worldwide. Despite a successful vaccination programme, the emergence of mutated variants that can escape current levels of immunity mean infections continue. Herein, we report the development of CT-P63, a broad-spectrum neutralizing monoclonal antibody. In vitro studies demonstrated potent neutralizing activity against the most prevalent variants, including Delta and the BA.1 and BA.2 sub-lineages of Omicron. In a transgenic mouse model, prophylactic CT-P63 significantly reduced wild-type viral titres in the respiratory tract and CT-P63 treatment proved efficacious against infection with Beta, Delta, and Omicron variants of SARS-CoV-2 with no detectable infectious virus in the lungs of treated animals. A randomized, double-blind, parallel-group, placebo-controlled, Phase I, single ascending dose study in healthy volunteers (NCT05017168) confirmed the safety, tolerability, and pharmacokinetics of CT-P63. Twenty-four participants were randomized and received the planned dose of CT-P63 or placebo. The safety and tolerability of CT-P63 were evaluated as primary objectives. Eight participants (33.3%) experienced a treatment-emergent adverse event (TEAE), including one grade ≥3 (blood creatine phosphokinase increased). There were no deaths, treatment-emergent serious adverse events, TEAEs of special interest, or TEAEs leading to study drug discontinuation in the CT-P63 groups. Serum CT-P63 concentrations rapidly peaked before declining in a biphasic manner and systemic exposure was dose proportional. Overall, CT-P63 was clinically safe and showed broad-spectrum neutralizing activity against SARS-CoV-2 variants in vitro and in vivo.

Correlation between serum markers in the second trimester and preterm birth before 34 weeks in asymptomatic twin pregnancies.

OBJECTIVE: To determine the correlation between the levels of serum markers in the second trimester and preterm birth before 34 weeks in asymptomatic twin pregnancies. METHODS: We conducted a retrospective review of the medical records of 102 asymptomatic twin pregnancies delivered at Chilgok Kyungpook National University Hospital between March 2014 and February 2020. Participants were divided into two groups, based on delivery before and after 34 weeks of gestation. Results of the quad test performed at 15-18 weeks and the complete blood count done at 24-28 weeks were compared. RESULTS: Preterm birth before 34 weeks of pregnancy was associated with higher levels of maternal α-fetoprotein (1.04 vs 0.98, multiple of median [MoM], P = 0.006), human chorionic gonadotropin (1.76 vs 1.31, MoM, P = 0.000), and inhibin A (1.78 vs 1.04, MoM, P = 0.000). Positive correlations were observed between gestational age at delivery and white blood cell (WBC) markers. Women with preterm delivery had decreased WBC counts (8180 vs 9405 × 103 /µl, P = 0.019) and neutrophil:lymphocyte ratios (3.85 vs 4.92, P = 0.001). CONCLUSION: Serum marker levels in the second trimester can be indicators of preterm delivery before 34 weeks in asymptomatic twin pregnancies.

Acupuncture for the treatment of overactive bladder: A systematic review and meta-analysis.

Background: Acupuncture (AT) successfully regulates overactive bladder (OAB) symptoms. However, previous systematic reviews and meta-analyses have not provided sufficient evidence. This review presents the current evidence of the efficacy of AT in the management of OAB symptoms. Methods and analyses: A total of 12 databases were searched from their inception: PubMed, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), and AMED databases; five Korean medical databases; and three Chinese medical databases. Study selection, data extraction, and assessment were independently performed by two researchers. The risk of bias was assessed using the Cochrane risk of bias assessment tool. RevMan 5.4.1 software was used for data aggregation, and the Grades of Recommendations, Assessment, Development and Evaluation (GRADE) assessment was used to evaluate the quality of the study outcomes. Results: A total of 30 studies were included in this review. Compared with the sham AT group, the AT group exhibited significant effects in reducing overactive bladder symptom scores (OABSS) [mean difference (MD): -1.13, 95% confidence interval (CI): -2.01 to -0.26, p = 0.01 I 2 = 67%] and urinary frequency [standardized mean difference (SMD): -0.35, 95% CI: -0.62 to -0.08, I 2 = 0%]. The AT group showed an equivalent effect as drug therapy in reducing OABSS (MD: -0.39, 95% CI: - 1.92 to 1.13, p = 0.61, I 2 = 94%) and urinary frequency (MD: 0.74, 95% CI: -0.00 to 1.48, p = 0.05, I 2 = 71%) with fewer adverse events [risk ratio (RR): 0.38, 95% CI: 0.16-0.92, p = 0.03, I2 = 58%]. The AT plus drug therapy group had a more favorable effect than drug therapy alone for reducing OABSS (MD: -2.28, 95% CI: -3.25 to -1.31, p < 0.00001, I 2 = 84%) and urinary frequency (MD: -2.34, 95% CI: -3.29 to -1.38, p < 0.00001, I 2 = 88%). The GRADE assessment demonstrated that the level of evidence was mostly low or very low given the high risk of bias and small sample sizes. Conclusion: AT had more favorable effects than sham AT in reducing OAB symptoms. AT improved OAB symptoms as effectively as conventional drug therapy, and the combination of AT and drug therapy had more favorable effects than drug therapy alone. However, more rigorous studies are needed to enhance the level of evidence. Systematic review registration: http://www.crd.york.ac.uk/PROSPERO/display_record.php?ID=CRD42014010377, identifier: PROSPERO [CRD42014010377].

Electroacupuncture for the treatment of frozen shoulder: A protocol for systematic review and meta-analysis.

BACKGROUND: Electroacupuncture has been reported to successfully control pain. Currently, no systematic reviews of the effects of electroacupuncture on frozen shoulder patients have been performed. This review aims to provide current evidence on the efficacy of electroacupuncture for the management of pain in frozen shoulder. METHODS AND ANALYSES: Eleven databases will be searched from their inception: PubMed, AMED, EMBASE, the Cochrane Library, 6 Korean medical databases, and 1 Chinese medical database. Study selection, data extraction, and assessment will be performed independently by 2 researchers. Risk of bias will be assessed using the Cochrane risk of bias assessment tool. ETHICS AND DISSEMINATION: Ethical approvals and patient consent are not required because the meta-analysis will be based on published research. This systematic review will be published in a peer-reviewed journal and disseminated both electronically and in print. The review will be updated to inform and guide health care practice and policy. TRIAL REGISTRATION NUMBER: PROSPERO 2021 CRD42021247090.

The in vitro and in vivo efficacy of CT-P59 against Gamma, Delta and its associated variants of SARS-CoV-2.

The SARS-CoV-2 variant is rapidly spreading across the world and causes to resurge infections. We previously reported that CT-P59 presented its in vivo potency against Beta variants, despite its reduced activity in cell experiments. Yet, it remains uncertain to exert the antiviral effect of CT-P59 on Gamma, Delta and its associated variants (L452R). To tackle this question, we carried out cell tests and animal studies. CT-P59 showed neutralization against Gamma, Delta, Epsilon, and Kappa variants in cells, with reduced susceptibility. The mouse challenge experiments with Gamma and Delta variants substantiated in vivo potency of CT-P59 showing symptom remission and virus abrogation in the respiratory tract. Collectively, cell and animal studies showed that CT-P59 is effective against Gamma and Delta variants infection, hinting that CT-P59 has therapeutic potential for patients infected with Gamma, Delta and its associated variants.

Staged Chest Wall Reconstruction for Radiation-induced Costochondritis.

Costochondritis after breast reconstruction and radiation therapy is rarely reported. Moreover, it is difficult to diagnose using computed tomography and magnetic resonance imaging; as such, wound debridement and reconstruction must be performed in several stages. A 51-year-old woman was diagnosed with invasive cancer of the right breast, and she underwent nipple sparing mastectomy and direct-to-implant breast reconstruction in November 2007. Thirteen years later, in September 2020, she experienced pain and swelling on her right breast. Incisional drainage and implant removal were performed in another clinic; however, the infection was not controlled. An implant-induced infection was suspected, and debridement was performed to a level where fresh tissue appeared in the upper layer of the intercostal muscle. Antibiotics and open dressing were used for 10 days; however, yellowish debris was noted, and third to fifth ribs and costal cartilages turned dark brown. Radiation-induced costochondritis was diagnosed based on clinical findings from the intraoperative field, wound course, and cartilage biopsy. Radical chest wall resection and reconstruction was performed using Teflon (Dupont/Chemours, Wilmington, Del.) and latissimus dorsi musculocutaneous flap. The patient was discharged 2 weeks after surgery without any complications. Costochondritis should be clinically diagnosed while performing the first debridement in staged operation. Radical chest wall resection is essential with chest wall reconstruction using Teflon and a latissimus dorsi musculocutaneous flap.

Therapeutic effect of CT-P59 against SARS-CoV-2 South African variant.

The global circulation of newly emerging variants of SARS-CoV-2 is a new threat to public health due to their increased transmissibility and immune evasion. Moreover, currently available vaccines and therapeutic antibodies were shown to be less effective against new variants, in particular, the South African (SA) variant, termed 501Y.V2 or B.1.351. To assess the efficacy of the CT-P59 monoclonal antibody against the SA variant, we sought to perform as in vitro binding and neutralization assays, and in vivo animal studies. CT-P59 neutralized B.1.1.7 variant to a similar extent as to wild type virus. CT-P59 showed reduced binding affinity against a RBD (receptor binding domain) triple mutant containing mutations defining B.1.351 (K417N/E484K/N501Y) also showed reduced potency against the SA variant in live virus and pseudovirus neutralization assay systems. However, in vivo ferret challenge studies demonstrated that a therapeutic dosage of CT-P59 was able to decrease B.1.351 viral load in the upper and lower respiratory tracts, comparable to that observed for the wild type virus. Overall, although CT-P59 showed reduced in vitro neutralizing activity against the SA variant, sufficient antiviral effect in B.1.351-infected animals was confirmed with a clinical dosage of CT-P59, suggesting that CT-P59 has therapeutic potential for COVID-19 patients infected with SA variant.

Phenotypic Discovery of SB1501, an Anti-obesity Agent, through Modulating Mitochondrial Activity.

Obesity has become a pandemic that threatens the quality of life and discovering novel therapeutic agents that can reverse obesity and obesity-related metabolic disorders are necessary. Here, we aimed to identify new anti-obesity agents using a phenotype-based approach. We performed image-based high-content screening with a fluorogenic bioprobe (SF44), which visualizes cellular lipid droplets (LDs), to identify initial hit compounds. A structure-activity relationship study led us to yield a bioactive compound SB1501, which reduces cellular LDs in 3T3-L1 adipocytes without cytotoxicity. SB1501 induced the expression of gene products that regulate mitochondrial biogenesis and fatty acid oxidation in 3T3-L1 adipocytes. Daily treatment with SB1501 improved the metabolic states of db/db mice by reducing body fat mass, adipose tissue mass, food intake, and increasing glucose tolerance. The anti-obesity effect of SB1501 may result from perturbation of the PGC-1α-UCP1 regulatory axis in inguinal white adipose tissue and brown adipose tissue. These data suggest the therapeutic potential of SB1501 as an anti-obesity agent via modulating mitochondrial activities.

A therapeutic neutralizing antibody targeting receptor binding domain of SARS-CoV-2 spike protein.

Vaccines and therapeutics are urgently needed for the pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here, we screen human monoclonal antibodies (mAb) targeting the receptor binding domain (RBD) of the viral spike protein via antibody library constructed from peripheral blood mononuclear cells of a convalescent patient. The CT-P59 mAb potently neutralizes SARS-CoV-2 isolates including the D614G variant without antibody-dependent enhancement effect. Complex crystal structure of CT-P59 Fab/RBD shows that CT-P59 blocks interaction regions of RBD for angiotensin converting enzyme 2 (ACE2) receptor with an orientation that is notably different from previously reported RBD-targeting mAbs. Furthermore, therapeutic effects of CT-P59 are evaluated in three animal models (ferret, hamster, and rhesus monkey), demonstrating a substantial reduction in viral titer along with alleviation of clinical symptoms. Therefore, CT-P59 may be a promising therapeutic candidate for COVID-19.

The diagnosis of an imperforate anus in female fetuses.

Imperforate anus is an anomaly caused by a defect in the development of the hindgut during early pregnancy. It is a relatively common congenital malformation and is more common in males. Although there are cases of a solitary imperforate anus, the condition is more commonly found as a part of a wider spectrum of other congenital anomalies. Although urgent reconstructive anorectal surgery is not necessary, immediate evaluation is important and urgent decompressive surgery may be required. Moreover, as there are often other anomalies that can affect management, prenatal diagnosis can help in optimizing perinatal care and prepare parents through prenatal counseling. In the past, imperforate anus was diagnosed by prenatal ultrasonography based on indirect signs such as bowel dilatation or intraluminal calcified meconium. Currently, it is diagnosed by directly checking the perineum with prenatal ultrasonography. Despite advances in ultrasound technology, accurate prenatal diagnosis is impossible in most cases and imperforate anus is detected after birth. Here, we present two cases of imperforate anus in female fetuses that were not diagnosed prenatally.

Sikyungbanha-Tang Suppressing Acute Lung Injury in Mice Is Related to the Activation of Nrf2 and TNFAIP3.

Sikyungbanha-Tang (SKBHT) is a Chinese traditional medicine popularly prescribed to patients with respiratory inflammatory symptoms in Korea. Although the Korea Food and Drug Administration approved SKBHT as a therapeutics for relieving the symptoms, experimental evidence for SKBHT suppressing inflammation is scarce. Here, we presented evidence that SKBHT can suppress inflammation in an acute lung injury (ALI) mouse model and explored the possible underlying mechanisms of SKBHT's anti-inflammatory activity. Single intratracheal (i.t.) injection of SKBHT (1 mg/kg or 10 mg/kg body weight) into mouse lungs decreased prototypic features of lung inflammation found in ALI, such as a high level of proinflammatory cytokines, neutrophil infiltration, and the formation of hyaline membrane, which were induced by a single i.t. LPS (2 mg/kg body weight). When added to a murine macrophage RAW 264.7 cells, SKBHT activated an anti-inflammatory factor Nrf2, increasing the expression of genes regulated by Nrf2. SKBHT suppressed the ubiquitination of Nrf2, suggesting that SKBHT increases the level of and thus activates Nrf2 by blunting the ubiquitin-dependent degradation of Nrf2. SKBHT induced the expression of tumor necrosis factor α-induced protein 3 (TNFAIP3), an ubiquitin-modulating protein that suppresses various cellular signals to NF-κB. Concordantly, SKBHT suppressed NF-κB activity and the expression of inflammatory cytokine genes regulated by NF-κB. Given that Nrf2 and TNFAIP3 are involved in regulating inflammation, our results suggest that SKBHT suppresses inflammation in the lung, the effect of which is related to SKBHT activating Nrf2 and TNFAIP3.

The methanol extract of Guettarda speciosa Linn. Ameliorates acute lung injury in mice.

BACKGROUND: Guettarda speciosa is mainly found in tropical areas in Asia. Although G. speciosa is traditionally used to treat some of the inflammatory disorders, the experimental evidence supporting the anti-inflammatory effect of G. speciosa is limited. Here, we sought to obtain evidence that G. speciosa has anti-inflammatory activity using an acute lung injury (ALI) mouse model and to explore possible underlying mechanisms for the activity. METHODS: The methanol extract of G. speciosa Linn. (MGS) was fingerprinted by HPLC. Cytotoxicity was determined by MTT and flow cytometer. As for an ALI mouse model, C57BL/6 mice received an intratracheal (i.t.) injection of lipopolysaccharide (LPS). The effects of MGS on lung inflammation in the ALI mice were assessed by differential cell counting and FACS of inflammatory cells and hematoxylin and eosin staining of lung tissue. Proteins were analyzed by immunoprecipitation and immunoblotting, and gene expression was by real-time qPCR. Neutrophil elastase activity was measured by ELISA. RESULTS: MGS did not cause metabolic disarray or produce reactive oxygen species that could induce cytotoxicity. Similar to ALI patients, C57BL/6 mice that received an i.t. LPS developed a high level of neutrophils, increased pro-inflammatory cytokines, and inflicted tissue damage in the lung, which was suppressed by i.t. MGS administered at 2 h after LPS. Mechanistically, MGS activated Nrf2, which was related to MGS interrupting the ubiquitin-dependent degradation of Nrf2. MGS suppressed the nuclear localization of NF-κB induced by LPS, suggesting the inhibition of NF-κB activity. Furthermore, MGS inhibited the enzymatic activity of neutrophil elastase. CONCLUSION: MGS could suppress lung inflammation in an ALI mouse model, the effect of which could be attributed to multiple mechanisms, including the activation of Nrf2 and the suppression of NF-κB and neutrophil elastase enzymatic activity by MGS.

Relationship between Cancer Stem Cell Marker CD133 and Cancer Germline Antigen Genes in NCI-H292 Lung Cancer Cells.

BACKGROUND: Previous studies have shown that lung cancer stem cells express CD133 and that certain cancer stem cells express cancer germline antigens (CGAs). The transcriptional regulation of CD133 is complicated and poorly understood. We investigated CD133 and CGA expression in a non-small cell lung cancer cell line. METHODS: The expression levels of CD133 and CGAs (MAGE-6, GAGE, SSX, and TRAG-3) were measured in an NCI-H292 lung cancer cell line. The methylation status of the CD133 gene promoter region was analyzed. The expression levels and promoter methylation statuses of CD133 and CGAs were confirmed by treatment with the demethylating agent 5-aza-2'-deoxycytidine (ADC). RESULTS: After treatment with ADC, CD133 expression was no longer detected. MAGE-6 and TRAG-3 were detected before ADC treatment, while GAGE and SSX were not detected. ADC treatment upregulated MAGE-6 and TRAG-3 expression, while GAGE expression was still undetected after treatment, and only weak SSX expression was observed. GAGE expression was not correlated with expression of CD133, while the levels of expression of MAGE-6, TRAG-3, and SSX were inversely correlated with CD133 expression. CONCLUSION: These results showed that CD133 expression can be regulated by methylation. Thus, the demethylation of the CD133 promoter may compromise the treatment of lung cancer by inactivating cancer stem cells and/or activating CGAs.

Activation of invariant natural killer T cells stimulates adipose tissue remodeling via adipocyte death and birth in obesity.

In obesity, adipose tissue undergoes dynamic remodeling processes such as adipocyte hypertrophy, hypoxia, immune responses, and adipocyte death. However, whether and how invariant natural killer T (iNKT) cells contribute to adipose tissue remodeling are elusive. In this study, we demonstrate that iNKT cells remove unhealthy adipocytes and stimulate the differentiation of healthy adipocytes. In obese adipose tissue, iNKT cells were abundantly found nearby dead adipocytes. FasL-positive adipose iNKT cells exerted cytotoxic effects to eliminate hypertrophic and pro-inflammatory Fas-positive adipocytes. Furthermore, in vivo adipocyte-lineage tracing mice model showed that activation of iNKT cells by alpha-galactosylceramide promoted adipocyte turnover, eventually leading to potentiation of the insulin-dependent glucose uptake ability in adipose tissue. Collectively, our data propose a novel role of adipose iNKT cells in the regulation of adipocyte turnover in obesity.

During Adipocyte Remodeling, Lipid Droplet Configurations Regulate Insulin Sensitivity through F-Actin and G-Actin Reorganization.

Adipocytes have unique morphological traits in insulin sensitivity control. However, how the appearance of adipocytes can determine insulin sensitivity has not been understood. Here, we demonstrate that actin cytoskeleton reorganization upon lipid droplet (LD) configurations in adipocytes plays important roles in insulin-dependent glucose uptake by regulating GLUT4 trafficking. Compared to white adipocytes, brown/beige adipocytes with multilocular LDs exhibited well-developed filamentous actin (F-actin) structure and potentiated GLUT4 translocation to the plasma membrane in the presence of insulin. In contrast, LD enlargement and unilocularization in adipocytes downregulated cortical F-actin formation, eventually leading to decreased F-actin-to-globular actin (G-actin) ratio and suppression of insulin-dependent GLUT4 trafficking. Pharmacological inhibition of actin polymerization accompanied with impaired F/G-actin dynamics reduced glucose uptake in adipose tissue and conferred systemic insulin resistance in mice. Thus, our study reveals that adipocyte remodeling with different LD configurations could be an important factor to determine insulin sensitivity by modulating F/G-actin dynamics.