In several human tumors, signal transducer and activator of transcription 3 (STAT3) and nuclear factor κB (NFκB) are activated and interact; how these STAT3–NFκB complexes are transported to the nucleus is not fully understood. In this study, we found that Rac1 was activated in starved cancer cells and that activated Rac1 coexisted with STAT3 and NFκB. Rac1 knockdown and overexpression of the dominant-negative mutant Rac1N19 inhibited the degradation of IκBα, an inhibitor of NFκB. MG132, an inhibitor of the ubiquitin proteasome pathway, increased the amount of non-phosphorylated IκBα, but not serine-phosphorylated IκBα, indicating that IκBα degradation by Rac1 in starved cancer cells is independent of IκBα serine phosphorylation by IKK. Rac1 knockdown also inhibited the nuclear translocation of STAT3–NFκB complexes, indicating that this translocation requires activated Rac1. We also demonstrated that the mutant STAT3 Y705F could form complexes with NFκB, and these unphosphorylated STAT3–NFκB complexes translocated into the nucleus and upregulated the activity of NFκB in starved cancer cells, suggesting that phosphorylation of STAT3 is not essential for its translocation. To our knowledge, this is the first study demonstrating the crucial role of Rac1 in the function of STAT3–NFκB complexes in starved cancer cells and implies that targeting Rac1 may have future therapeutic significance in cancer therapy.
Humans ; Phosphorylation ; Proteasome Endopeptidase Complex ; Serine ; STAT3 Transcription Factor ; Ubiquitin

High mobility group-1 (HMGB-1) enhances the DNA interactions and possesses a transcriptional activation potential for several families of sequence-specific transcriptional activators. In order to examine the effect of HMGB-1 on the cell cycle progression in MCF-7 cells, the HMGB-1 expression vector was transfected into synchronized MCF-7 cells, and the effect of HMGB-1 overexpression on the cell cycle was examined. The HMGB-1 protein level in the transfected cells increased 4.87-fold compared to the non-transfected cells. There were few changes in the cell cycle phase distribution after HMGB-1 overexpression in the MCF-7 cells. Following the estrogen treatment, the cell cycle progressed in both the HMGB-1 overexpressed MCF-7 and the mock-treated cells. However, a larger proportion of HMGB-1 overexpressing MCF-7 cells progressed to the either S or G2 phase than the mock-treated cells. The mRNA levels of the cell cycle regulators changed after being treated with estrogen in both the HMGB-1 overexpressing MCF-7 and the mock-treated cells, but the changes in the expression level of the cell cycle regulator genes were more prominent in the HMGB-1 overexpressing MCF-7 cells than in the mock-treated cells. In conclusion, HMGB-1 overexpression itself does not alter the MCF-7 cell cycle progression, but the addition of estrogen to the HMGB-1 overexpressing MCF-7 cells appears to accelerate the cell cycle progression.
Blotting, Western ; Cell Cycle ; Cell Line, Tumor ; Densitometry ; Estrogens/metabolism ; G2 Phase ; Genetic Vectors ; HMGB1 Protein/*biosynthesis ; Human ; Kinetics ; Oligonucleotides/chemistry ; Plasmids/metabolism ; Protein Structure, Tertiary ; RNA, Messenger/metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; S Phase ; Support, Non-U.S. Gov't ; Time Factors ; Trans-Activation (Genetics) ; Transfection

We systematically reviewed radiological abnormalities in patients with prolonged SARS-CoV-2 infection, defined as persistently positive polymerase chain reaction (PCR) results for SARS-CoV-2 for > 21 days, with either persistent or relapsed symptoms. We extracted data from 24 patients (median age, 54.5 [interquartile range, 44–64 years]) reported in the literature and analyzed their representative CT images based on the timing of the CT scan relative to the initial PCR positivity. Our analysis focused on the patterns and distribution of CT findings, severity scores of lung involvement on a scale of 0–4, and the presence of migration. All patients were immunocompromised, including 62.5% (15/24) with underlying lymphoma and 83.3% (20/24) who had received anti-CD20 therapy within one year. Median duration of infection was 90 days. Most patients exhibited typical CT appearance of coronavirus disease 19 (COVID-19), including ground-glass opacities with or without consolidation, throughout the follow-up period. Notably, CT severity scores were significantly lower during ≤ 21 days than during > 21 days (P < 0.001). Migration was observed on CT in 22.7% (5/22) of patients at ≤ 21 days and in 68.2% (15/22) to 87.5% (14/16) of patients at > 21 days, with rare instances of parenchymal bands in previously affected areas. Prolonged SARS-CoV-2 infection usually presents as migrating typical COVID-19 pneumonia in immunocompromised patients, especially those with impaired B-cell immunity.

PURPOSE: When murine myeloma cells P3-X63-Ag8.653 (V653) of this model treated with amin opterin, an anticancer drug, they can't synthesize nucleic acid via de novo or salvage pathway and selectively eliminated due to apoptosis. This study was aimed to clone specific known and novel genes preferentially expressed in aminopteirn-treated tumor cell apoptosis. MATERIALS AND METHODS: This study was aimed to clone specific known and novel genes pre ferentially expressed in aminopteirn-treated tumor cell apoptosis by using subtraction-PCR technique. RESULTS: By using this technique 868 clones were obtained. Of these 427 clones were positive with insert DNA. By using cross-hybridization Southern blotting, final 101 clones were selected. All of these genes were sequenced and analyzed by using genebank DNA database. Total 101 clones of genes preferentially expressed in apoptotic tumor cells were classified into 10 groups, which included ribosomal proteins, nuclear proteins, mitdegrees Chondrial proteins, signal transductional proteins, retroviral proteins, cell surface receptor proteins, cell structural proteins, unclassified miscellaneous proteins, and novel genes. Especially, Unknown novel genes preferentially ex pressed in this apoptotic tumor cells included clone numbers S1-63, 1-1, 1-3, 1-16, 1-18, 1-20, 3-33, 3-41, 3-44, 3-48, 3-55, 3-60, 6-17, 6-25, 8-12, 50-7, 50-23, and 100-35. CONCLUSION: It seemed that known and unknown novel genes cloned in this study would con tribute to the future studies regarding apoptosis of tumor cells and cancer treatment therepy.
Aminopterin ; Apoptosis* ; Blotting, Southern ; Clone Cells* ; Cloning, Organism* ; Databases, Nucleic Acid ; DNA ; Mass Screening* ; Membrane Proteins ; Nuclear Proteins ; Ribosomal Proteins ; Zidovudine

Surgery is the standard treatment for a primary gastrointestinal stromal tumor (GIST); however, surgical resection is often not curative, particularly for large GISTs. In the past decade, with imatinib mesylate (IM), management strategies for GISTs have evolved significantly, and now IM is the standard care for patients with locally advanced, recurrent or metastatic GISTs. Adjuvant therapy with imatinib was recently approved for use, and preoperative imatinib is an emerging treatment option for patients who require cytoreductive therapy. IM neoadjuvant therapy for primary GISTs has been reported, but there is no consensus on the dose of the drug, the duration of treatment and the optimal time of surgery. These are critical because drug resistance or tumor progression can develop with a prolonged treatment. This report describes two cases of large rectal malignant GISTs, for which a abdominoperineal resection was initially anticipated. The two patients received IM preoperative treatment; we followed-up with CT or magnetic resonance imaging to access the response. After 9 months of treatment, a multi-disciplinary consensus that maximal benefit from imatinib had been achieved was reached. We determined the best time for surgical intervention and successfully performed sphincter-preserving surgery before resistance to imatinib or tumor progression occurred. We believe that a multidisciplinary team approach, considerating the optimal duration of therapy and the timing of surgery, is required to optimize treatment outcome.
Benzamides ; Consensus ; Drug Resistance ; Gastrointestinal Stromal Tumors ; Humans ; Imatinib Mesylate ; Magnetic Resonance Imaging ; Mesylates ; Neoadjuvant Therapy ; Piperazines ; Pyrimidines ; Treatment Outcome

Objective: Because of the exceptionally high suicide rates in South Korea, new assessment methods are needed to improve suicide prevention. The current study aims to validate the revised Suicide Crisis Inventory-2 (SCI-2), a self-report measure that assesses a cognitiveaffective pre-suicidal state in a Korean sample. Methods: With data from 1,061 community adults in South Korea, confirmatory factor analyses were first conducted to test the proposed one-factor and five-factor structures of the SCI-2. Also, an exploratory factor analysis (EFA) was performed to examine possible alternative factor structure of the inventory. Results: The one-factor model of the SCI-2 resulted in good model fit and similarly, the five-factor model also exhibited strong fit. Comparing the two models, the five-factor was evaluated as the superior model fit. An alternative 4-factor model derived from EFA exhibited a comparable model fit. The Korean version of the SCI-2 had high internal consistency and strong concurrent validity in relation to symptoms of suicidal ideation, depression, and anxiety. Conclusion The SCI-2 is an appropriate and a valid tool for measuring one’s proximity to imminent suicide risk. However, the exact factor structure of the SCI-2 may be culture-sensitive and warrants further study.

Purpose: This study examined the prevalence of metabolic syndrome (MetS) in South Korean children and adolescents by gender and age and analyzed gender-specific factors associated with MetS. Methods: This study used data on children aged 10~18 from the Korea National Health and Nutrition Examination Survey (KNHANES) from 2010 to 2015. Analyses included descriptive statistics, the independent t-test, the x2 test, and univariate logistic regression analysis (p<.050). Results: The prevalence of MetS was 4.8% in boys and 3.4% in girls. The prevalence was higher in girls up to the age of 12, but higher in boys who were 13 or older. Abdominal obesity was frequent in girls, whereas low high-density lipoprotein cholesterol (HDL-C) and elevated blood pressure were more common in boys. Higher body mass index, waist-to-height ratio, waist circumference, blood pressure, triglycerides, HDL-C, perceived "fat" body shape, and weight loss efforts were associated with MetS in both genders. Increasing age, having one meal per day, and weight maintenance were associated factors unique to boys. Fasting plasma glucose, familial medical history of low HDL-C, and perceived "thin" body shape were associated factors in girls. Conclusion Gender and age differences should be considered in the risk assessment and prevention of MetS.

In brain tissue, astrocytes play defensive roles in central nervous system integrity by mediating immune responses against pathological conditions. Type I phosphatidylinositol 4-phosphate 5-kinase alpha (PIP5Kalpha) that is responsible for production of phosphatidylinositol 4,5-bisphosphate (PI[4,5]P2) regulates many important cell functions at the cell surface. Here, we have examined whether PIP5Kalpha is associated with astrocyte inflammatory responses. Gangliosides are releasable from damaged cell membranes of neurons and capable of inducing inflammatory responses. We found that treatment of primary cultured astrocytes with gangliosides significantly enhanced PIP5Kalpha mRNA and protein expression levels. PI(4,5)P2 imaging using a fluorescent tubby (R332H) expression as a PI(4,5)P2-specific probe showed that ganglioside treatment increased PI(4,5)P2 level. Interestingly, microRNA-based PIP5Kalpha knockdown strongly reduced ganglioside-induced transcription of proinflammatory cytokines IL-1beta and TNFalpha. PIP5Kalpha knockdown also suppressed ganglioside-induced phosphorylation and nuclear translocation of NF-kappaB and the degradation of IkappaB-alpha, indicating that PIP5Kalpha knockdown interfered with the ganglioside-activated NF-kappaB signaling. Together, these results suggest that PIP5Kalpha is a novel inflammatory mediator that undergoes upregulation and contributes to immune responses by facilitating NF-kappaB activation in ganglioside-stimulated astrocytes.
Animals ; Astrocytes/*metabolism ; Cells, Cultured ; Gangliosides/*metabolism ; Gene Knockdown Techniques ; Inflammation/*metabolism ; Interleukin-1/metabolism ; NF-kappa B/metabolism ; Phosphotransferases (Alcohol Group Acceptor)/*metabolism ; RNA, Messenger/*genetics/metabolism ; Rats ; Rats, Sprague-Dawley ; Signal Transduction ; Tumor Necrosis Factor-alpha/metabolism ; Up-Regulation

BACKGROUND/AIMS: There has been controversy about the role of Toll-like receptor 2 (TLR2) in renal injury following ureteric obstruction. Although inhibition of the renin angiotensin system (RAS) reduces TLR2 expression in mice, the exact relationship between TLR2 and RAS is not known. The aim of this study was to determine whether the RAS modulates TLR2. METHODS: We used 8-week-old male wild type (WT) and TLR2-knockout (KO) mice on a C57Bl/6 background. Unilateral ureteral obstruction (UUO) was induced by complete ligation of the left ureter. Angiotensin (Ang) II (1,000 ng/kg/min) and the direct renin inhibitor aliskiren (25 mg/kg/day) were administrated to mice using an osmotic minipump. Molecular and histologic evaluations were performed. RESULTS: Ang II infusion increased mRNA expression of TLR2 in WT mouse kidneys (p < 0.05). The expression of renin mRNA in TLR2-KO UUO kidneys was significantly higher than that in WT UUO kidneys (p < 0.05). There were no differences in tissue injury score or mRNA expression of monocyte chemotactic protein 1 (MCP-1), osteopontin (OPN), or transforming growth factor beta (TGF-beta) between TLR2-KO UUO and WT UUO kidneys. However, aliskiren decreased the tissue injury score and mRNA expression of TLR2, MCP-1, OPN, and TGF-beta in WT UUO kidneys (p < 0.05). Aliskiren-treated TLR2-KO UUO kidneys showed less kidney injury than aliskiren-treated WT UUO kidneys. CONCLUSIONS: TLR2 deletion induced activation of the RAS in UUO kidneys. Moreover, inhibition of both RAS and TLR2 had an additive ameliorative effect on UUO injury of the kidney.
Amides/*pharmacology ; Angiotensin II/pharmacology ; Animals ; Disease Models, Animal ; Fibrosis ; Fumarates/*pharmacology ; Kidney/*drug effects/metabolism/pathology ; Male ; Mice, Inbred C57BL ; Mice, Knockout ; Nephritis, Interstitial/genetics/metabolism/pathology/*prevention & control ; RNA, Messenger/genetics/metabolism ; Renin/*antagonists & inhibitors/metabolism ; Renin-Angiotensin System/*drug effects ; Toll-Like Receptor 2/deficiency/drug effects/genetics/*metabolism ; Ureteral Obstruction/*drug therapy/genetics/metabolism/pathology

Intracranial manifestations associated with autosomal dominant polycystic kidney disease (ADPKD) include arachnoid cysts, dolichoectasias, and subdural hematoma (SDH), although there are only a few reports of SDH in patients with ADPKD. We report a case of spontaneous SDH in a patient with ADPKD. A 33-year-old woman complained of severe nausea and vomiting for 10 days. She had suffered from a headache for several months. She was diagnosed with ADPKD and hypertension 6 years earlier, and the hypertension was well controlled. Her mental state was drowsy in the emergency room. Her blood pressure was 180/105 mmHg. There was no evidence of head trauma. Results of a peripheral blood CBC and blood chemistry analysis were within normal limits, as were the results of a blood coagulation test and urinalysis. She was pregnant and in the eighth week of gestation. Brain magnetic resonance imaging revealed SDH in the left lateral convexity and focally in the right lateral convexity, and brain herniation. Surgical drainage was performed through a burr hole, under general anesthesia. Intra-operatively, 62 mL of liquefied subdural hematoma were removed. She recovered completely without sequelae.
Adult ; Anesthesia, General ; Arachnoid Cysts ; Blood Coagulation Tests ; Blood Pressure ; Brain ; Craniocerebral Trauma ; Drainage ; Emergencies ; Female ; Headache ; Hematoma, Subdural ; Humans ; Hypertension ; Magnetic Resonance Imaging ; Nausea ; Polycystic Kidney, Autosomal Dominant ; Pregnancy ; Urinalysis ; Vomiting