Identification of benzo[b]thiophene-1,1-dioxide derivatives as novel PHGDH covalent inhibitors.

The increased de novo serine biosynthesis confers many advantages for tumorigenesis and metastasis. Phosphoglycerate dehydrogenase (PHGDH), a rate-limiting enzyme in serine biogenesis, exhibits hyperactivity across multiple tumors and emerges as a promising target for cancer treatment. Through screening our in-house compound library, we identified compound Stattic as a potent PHGDH inhibitor (IC = 1.

Identifying the pathophysiological traits of obstructive sleep apnea during dexmedetomidine sedation.

Dexmedetomidine (DEX) has been described as a safe sedative in clinical practice, but its effects on the pathophysiological traits of obstructive sleep apnea (OSA) are unclear. We estimated the effects of DEX sedation on the four key pathophysiological traits of OSA (pharyngeal collapsibility, dilator muscle function, arousal threshold, and loop gain) in adult patients with OSA by conducting a secondary analysis of a prospective diagnostic trial. Pathophysiological traits estimated from polysomnography and the respiratory parameters under natural sleep and DEX-induced sleep were compared.

SUMO specific peptidase 3 halts pancreatic ductal adenocarcinoma metastasis via deSUMOylating DKC1.

In the past few decades, advances in the outcomes of patients suffering from pancreatic ductal adenocarcinoma (PDAC) have lagged behind these gained in the treatment of many other malignancies. Although the pivotal role of the SUMO pathway in PDAC has been illustrated, the underlying molecule drivers have yet to be fully elucidated. In the present study, we identified SENP3 as a potential suppressor of PDAC progression through an in vivo metastatic model.

Case report: Image guidance retrieval of a foreign body in retropharyngeal space.

Background: Ingested foreign bodies fully embedded in retropharyngeal space present a unique challenge, as they can be difficult to locate and visualize classic transoral laryngoscopy or the transcervical approach.

Methods: We retrieved a complete extraluminal chicken bone located in the patient's retropharyngeal space at the level of the C4-C5 spine through a well-designed transcervical approach with a combination of image-guided neck navigation.

Conclusion: A combined use of image-guided neck navigation and a dedicated transcervical approach for location of a foreign body in the retropharyngeal space is practical and available for clinical application.

Pregnancy outcomes in different stages of systemic lupus erythematosus among Chinese women - a retrospective cohort study.

Objectives: To analyze the outcomes of pregnancies and risk factors in Chinese women with different stages of systemic lupus erythematosus (SLE).

Material And Methods: A total of 55 conceptions in 52 patients with SLE between Jan 2007 and Jan 2019 were retrospected systematically from a general hospital graded 3A in China. Medical records provided us a good way to retrieve the clinical parameters and lab data of patients.

The interval between onset and admission predicts disease progression in COVID-19 patients.

Background: The prognostic role of the interval between disease onset and hospital admission (O-A interval) was undetermined in patients with the coronavirus disease 2019 (COVID-19).

Methods: A total of 205 laboratory-confirmed inpatients admitted to Hankou hospital of Wuhan from January 11 to March 8, 2020 were consecutively included in this retrospective observational study. Demographic data, medical history, laboratory testing results were collected from medical records.

The deubiquitinase USP44 promotes Treg function during inflammation by preventing FOXP3 degradation.

The transcription factor forkhead box P3 (FOXP3) is essential for the development of regulatory T cells (Tregs) and their function in immune homeostasis. Previous studies have shown that in natural Tregs (nTregs), FOXP3 can be regulated by polyubiquitination and deubiquitination. However, the molecular players active in this pathway, especially those modulating FOXP3 by deubiquitination in the distinct induced Treg (iTreg) lineage, remain unclear.

The Long Non-Coding RNA MALAT1 Enhances Ovarian Cancer Cell Stemness by Inhibiting YAP Translocation from Nucleus to Cytoplasm.

BACKGROUND The purpose of this work was to unearth the effects and underlying mechanism of long non-coding RNA (lncRNA) MALAT1 in ovarian cancer cell stemness. MATERIAL AND METHODS Western blot, quantitative polymerase chain reaction (qPCR) and sphere forming analysis were performed to evaluate the stem-like traits of cells and MALAT1-induced effects on ovarian cancer cell stemness. Cell viability was performed to evaluate MALAT1 role in the chemoresistance of ovarian cancer cells.

Poly-functional T helper cells in human tonsillar mononuclear cells.

Tonsils are important lymphoid organs in which B cells and T cells complete their maturation and identify cells that are infected by pathogens. However, the functions of T cells in human tonsils remain unclear, especially the characteristics of polyfunctional CD4 T helper cells. In this study, we used multi-color flow cytometry to analyze the expression or co-expression of effector cytokines in CD4 T cells from tonsillar tissues.

Nemo-like Kinase Drives Foxp3 Stability and Is Critical for Maintenance of Immune Tolerance by Regulatory T Cells.

The Foxp3 transcription factor is a crucial determinant of both regulatory T (T) cell development and their functional maintenance. Appropriate modulation of tolerogenic immune responses therefore requires the tight regulation of Foxp3 transcriptional output, and this involves both transcriptional and post-translational regulation. Here, we show that during T cell activation, phosphorylation of Foxp3 in T cells can be regulated by a TGF-β activated kinase 1 (TAK1)-Nemo-like kinase (NLK) signaling pathway.

Excessive periostin expression and Th2 response in patients with nasal polyps: association with asthma.

Background: Periostin has been shown to be upregulated in chronic rhinosinusitis with nasal polyps (CRSwNP), especially in the CRSwNP patients with asthma. However, the underlying mechanism that how periostin contributes to the polyp genesis remains unclear.

Methods: In this study, we collected 63 CRSwNP patients' nasal polyps (NPs) and 25 control subjects' uncinated tissues.

Stromal interleukin-33 promotes regulatory T cell-mediated immunosuppression in head and neck squamous cell carcinoma and correlates with poor prognosis.

Regulatory T cells (Tregs) mediate immunosuppressive signals that can contribute to the progression of head and neck squamous cell carcinoma (HNSCC). Interleukin-33 (IL-33) is defined as an 'alarmin', an endogenous factor that is expressed during tissue and cell damage, which has been shown to promote Treg proliferation in non-lymphoid organs. However, the interaction between IL-33 and Tregs in the HNSCC tumor microenvironment remains uncertain.

YAP Is Essential for Treg-Mediated Suppression of Antitumor Immunity.

Regulatory T cells (Treg) are critical for maintaining self-tolerance and immune homeostasis, but their suppressive function can impede effective antitumor immune responses. FOXP3 is a transcription factor expressed in Tregs that is required for their function. However, the pathways and microenvironmental cues governing FOXP3 expression and Treg function are not completely understood.

MicroRNA-17 Modulates Regulatory T Cell Function by Targeting Co-regulators of the Foxp3 Transcription Factor.

Regulatory T (Treg) cells are important in maintaining self-tolerance and immune homeostasis. The Treg cell transcription factor Foxp3 works in concert with other co-regulatory molecules, including Eos, to determine the transcriptional signature and characteristic suppressive phenotype of Treg cells. Here, we report that the inflammatory cytokine interleukin-6 (IL-6) actively repressed Eos expression through microRNA-17 (miR-17).

Increased Expression of miR-146a in Children With Allergic Rhinitis After Allergen-Specific Immunotherapy.

Purpose: MicroRNAs (miRs) were recently recognized to be important for immune cell differentiation and immune regulation. However, whether miRs were involved in allergen-specific immunotherapy (SIT) remains largely unknown. This study sought to examine changes in miR-146a and T regulatory cells in children with persistent allergic rhinitis (AR) after 3 months of subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT).

Expression of leukotriene and its receptors in eosinophilic chronic rhinosinusitis with nasal polyps.

Background: Cysteinyl leukotriene (LT) has been proposed in the pathogenesis of chronic rhinosinusitis with nasal polyps (CRSwNP). This study sought to examine the expression of the LT receptor (LTR) in CRSwNP patients and evaluate the potential role of LTR antagonist (LTRA) in the management of eosinophilic CRSwNP (ECRS) patients.

Methods: Nasal polyps and uncinate process tissues were collected from 18 ECRS patients, 13 non-eosinophilic CRSwNP (non-ECRS) patients, and 16 control subjects.

Human IL-21+IFN-γ+CD4+ T cells in nasal polyps are regulated by IL-12.

In the previous study, we found that the levels of IL-21 in nasal polyps (NPs) were significantly increased and associated with polyp size and recurrence. However, it is unclear that the cell source of IL-21 and the regulation of IL-21 in NP tissues. In the present study, we isolated the lymphocytes from NP tissues, uncinate tissues and peripheral blood of patients with NPs.

Expression of heme oxygenase-1 in eosinophilic and non-eosinophilic chronic rhinosinusitis with nasal polyps: modulation by cytokines.

Background: Oxidative stress is characteristic of chronic airway inflammatory diseases such as asthma, chronic obstructive pulmonary disease and chronic rhinosinusitis with nasal polyps (CRSwNP). Heme oxygenase (HO)-1 has been proposed to be a cytoprotective enzyme against oxidative stress in CRSwNP. However, the expression and regulation of HO-1 in eosinophilic CRSwNP (ECRS) and non-eosinophilic CRSwNP (non-ECRS) subsets has not been well documented.

Expression and Regulation of Transcription Factor FoxA2 in Chronic Rhinosinusitis With and Without Nasal Polyps.

Purpose: Chronic rhinosinusitis (CRS) is characterized by the excessive production of mucus. However, the molecular mechanism underlying mucin overproduction in CRS with or without nasal polyps (CRSwNP and CRSsNP, respectively) is poorly understood. This study was conducted to assess the importance of the transcription factor FoxA2 in mucin production and to investigate the targeting of FoxA2 as a potential therapeutic strategy for mucus hypersecretion in CRS patients.

Corticosteroid regulates epithelial occludin expression in nasal polyps through a MKP-1-dependent pathway.

Objective: To evaluate the regulatory effect of corticosteroid on occludin expression in polyp tissues of chronic rhinosinusitis with nasal polyps (CRSwNP) patients and in vitro.

Methods: Twenty CRSwNP patients were enrolled and subjected to prednisone (30 mg/day for 14 days). The expression of occludin in polyp tissues was examined before and after treatment using immunohistochemical staining and quantitative reverse transcription polymerase chain reaction.

Enhanced expression of SAM-pointed domain-containing Ets-like factor in chronic rhinosinusitis with nasal polyps.

Objective/hypothesis: Chronic rhinosinusitis with nasal polyps (CRSwNP) is characterized by significant goblet hyperplasia and mucus hypersecretion. However, the molecular mechanism underlying mucin overexpression in CRSwNP has not been well characterized. This study sought to assess the expression of SAM-pointed domain-containing Ets-like factor (SPDEF) and its regulation of mucin production in CRSwNP patients.

Azelastine enhances the clinical efficacy of glucocorticoid by modulating MKP-1 expression in allergic rhinitis.

Azelastine was suggested as a supplementary choice of glucocorticoid for the control of moderate to severe allergic rhinitis (AR). However, the underlying mechanism has not been completely understood. In this study, primary cultured nasal epithelial cells and bronchial epithelial cells were stimulated with proinflammatory cytokines (IL-1β and IL-17A) and anti-inflammatory agents (azelastine and budesonide) in vitro.