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  • 1
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    Online Resource
    The Usefulness of the Athens Insomnia Scale for Evaluating Sleep Disturbance in Patients with Chronic Liver Disease Comparing with Pittsburgh Sleep Quality Index and Epworth Sleepiness Scale
    MDPI AG ; 2022
    In:  Medicina Vol. 58, No. 6 ( 2022-05-30), p. 741-
    Details
    In: Medicina, MDPI AG, Vol. 58, No. 6 ( 2022-05-30), p. 741-
    Abstract: Background and Objectives: Sleep disturbance due to muscle cramps or hepatic encephalopathy in patients with chronic liver disease (CLD) can lead to a reduced quality of life. The Pittsburgh sleep quality index (PSQI) is commonly used for evaluating sleep disturbance; however, this questionnaire is time-consuming owing to the large number of questions. As the usefulness of the Athens insomnia scale (AIS) in patients with CLD is not sufficiently known, the present study aimed to determine whether the AIS and Epworth sleepiness scale (ESS) could be used as simple alternative questionnaires for evaluating sleep disturbances in patients with CLD. Materials and Methods: A total of 117 patients with CLD were retrospectively evaluated. Patients with overt hepatic encephalopathy were excluded. All patients were examined using the AIS, PSQI, and ESS, and their responses to these questionnaires were statistically analyzed. Results: The number of patients diagnosed with sleep disturbance using the AIS, PSQI, and ESS were 39 (33.3%), 37 (31.6%), and 9 (7.7%), respectively. There was no correlation between PSQI and ESS scores (r = 0.011, p = 0.910); in contrast, the AIS scores showed a significant correlation with the PSQI scores (r = 0.689, p 〈 0.001). When the PSQI was considered as the standard for evaluating sleep disturbance, the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the AIS were 76.9%, 91.0%, 81.1%, and 88.8%, respectively. In the sleep medication group, the sensitivity, specificity, PPV, and NPV of the AIS were 100%, 70%, 78.6%, and 100%, respectively. Conclusions: This is the first report to indicate that the AIS is an alternative questionnaire to the PSQI and that it can be a useful tool for detecting cirrhosis-related complications in patients with CLD.
    Type of Medium: Online Resource
    ISSN: 1648-9144
    URL: Article
    DOI: 10.3390/medicina58060741
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2088820-X
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  • 2
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    Metaplasia in the Stomach—Precursor of Gastric Cancer?
    MDPI AG ; 2017
    In:  International Journal of Molecular Sciences Vol. 18, No. 10 ( 2017-09-27), p. 2063-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 18, No. 10 ( 2017-09-27), p. 2063-
    Type of Medium: Online Resource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms18102063
    Language: English
    Publisher: MDPI AG
    Publication Date: 2017
    detail.hit.zdb_id: 2019364-6
    SSG: 12
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  • 3
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    Dysregulated Immune Responses by ASK1 Deficiency Alter Epithelial Progenitor Cell Fate and Accelerate Metaplasia Development during H. pylori Infection
    MDPI AG ; 2020
    In:  Microorganisms Vol. 8, No. 12 ( 2020-12-14), p. 1995-
    Details
    In: Microorganisms, MDPI AG, Vol. 8, No. 12 ( 2020-12-14), p. 1995-
    Abstract: The mechanism of H. pylori-induced atrophy and metaplasia has not been fully understood. Here, we demonstrate the novel role of Apoptosis signal-regulating kinase 1 (ASK1) and downstream MAPKs as a regulator of host immune responses and epithelial maintenance against H. pylori infection. ASK1 gene deficiency resulted in enhanced inflammation with numerous inflammatory cells including Gr-1+CD11b+ myeloid-derived suppressor cells (MDSCs) recruited into the infected stomach. Increase of IL-1β release from apoptotic macrophages and enhancement of TH1-polarized immune responses caused STAT1 and NF-κB activation in epithelial cells in ASK1 knockout mice. Dysregulated immune and epithelial activation in ASK1 knockout mice led to dramatic expansion of gastric progenitor cells and massive metaplasia development. Bone marrow transplantation experiments revealed that ASK1 in inflammatory cells is critical for inducing immune disorder and metaplastic changes in epithelium, while ASK1 in epithelial cells regulates cell proliferation in stem/progenitor zone without changes in inflammation and differentiation. These results suggest that H. pylori-induced immune cells may regulate epithelial homeostasis and cell fate as an inflammatory niche via ASK1 signaling.
    Type of Medium: Online Resource
    ISSN: 2076-2607
    URL: Article
    DOI: 10.3390/microorganisms8121995
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2720891-6
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  • 4
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    Screening Strategy of Pancreatic Cancer in Patients with Diabetes Mellitus
    MDPI AG ; 2020
    In:  Diagnostics Vol. 10, No. 8 ( 2020-08-08), p. 572-
    Details
    In: Diagnostics, MDPI AG, Vol. 10, No. 8 ( 2020-08-08), p. 572-
    Abstract: The incidence of pancreatic cancer (PCa) is increasing worldwide and has become one of the leading causes of cancer-related death. Screening for high risk populations is fundamental to overcome this intractable malignancy. Diabetes mellitus (DM) is classically known as a risk factor for PCa. Recently the reverse causality is in the spotlight, that is to say, DM is considered to be a manifestation of PCa. Numbers of epidemiological studies clarified that new-onset DM (≤2-year duration) was predominant in PCa patients and the relative risk for PCa inversely correlated with duration of DM. Among patients with new-onset DM, elder onset, weight loss, and rapid exacerbation of glycemic control were reported to be promising risk factors and signs, and the model was developed by combining these factors. Several pilot studies disclosed the possible utility of biomarkers to discriminate PCa-associated DM from type 2 DM. However, there is no reliable biomarkers to be used in the practice. We previously reported the application of a multivariate index for PCa based on the profile of plasma free amino acids (PFAAs) among diabetic patients. We are further investigating on the PFAA profile of PCa-associated DM, and it can be useful for developing the novel biomarker in the near future.
    Type of Medium: Online Resource
    ISSN: 2075-4418
    URL: Article
    DOI: 10.3390/diagnostics10080572
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2662336-5
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  • 5
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    Plasticity of Intestinal Epithelium: Stem Cell Niches and Regulatory Signals
    MDPI AG ; 2020
    In:  International Journal of Molecular Sciences Vol. 22, No. 1 ( 2020-12-31), p. 357-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 22, No. 1 ( 2020-12-31), p. 357-
    Abstract: The discovery of Lgr5+ intestinal stem cells (ISCs) triggered a breakthrough in the field of ISC research. Lgr5+ ISCs maintain the homeostasis of the intestinal epithelium in the steady state, while these cells are susceptible to epithelial damage induced by chemicals, pathogens, or irradiation. During the regeneration process of the intestinal epithelium, more quiescent +4 stem cells and short-lived transit-amplifying (TA) progenitor cells residing above Lgr5+ ISCs undergo dedifferentiation and act as stem-like cells. In addition, several recent reports have shown that a subset of terminally differentiated cells, including Paneth cells, tuft cells, or enteroendocrine cells, may also have some degree of plasticity in specific situations. The function of ISCs is maintained by the neighboring stem cell niches, which strictly regulate the key signal pathways in ISCs. In addition, various inflammatory cytokines play critical roles in intestinal regeneration and stem cell functions following epithelial injury. Here, we summarize the current understanding of ISCs and their niches, review recent findings regarding cellular plasticity and its regulatory mechanism, and discuss how inflammatory cytokines contribute to epithelial regeneration.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms22010357
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2019364-6
    SSG: 12
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  • 6
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    Lipid Metabolism in Oncology: Why It Matters, How to Research, and How to Treat
    MDPI AG ; 2021
    In:  Cancers Vol. 13, No. 3 ( 2021-01-26), p. 474-
    Details
    In: Cancers, MDPI AG, Vol. 13, No. 3 ( 2021-01-26), p. 474-
    Abstract: Lipids in our body, which are mainly composed of fatty acids, triacylglycerides, sphingolipids, phospholipids, and cholesterol, play important roles at the cellular level. In addition to being energy sources and structural components of biological membranes, several types of lipids serve as signaling molecules or secondary messengers. Metabolic reprogramming has been recognized as a hallmark of cancer, but changes in lipid metabolism in cancer have received less attention compared to glucose or glutamine metabolism. However, recent innovations in mass spectrometry- and chromatography-based lipidomics technologies have increased our understanding of the role of lipids in cancer. Changes in lipid metabolism, so-called “lipid metabolic reprogramming”, can affect cellular functions including the cell cycle, proliferation, growth, and differentiation, leading to carcinogenesis. Moreover, interactions between cancer cells and adjacent immune cells through altered lipid metabolism are known to support tumor growth and progression. Characterization of cancer-specific lipid metabolism can be used to identify novel metabolic targets for cancer treatment, and indeed, several clinical trials are currently underway. Thus, we discuss the latest findings on the roles of lipid metabolism in cancer biology and introduce current advances in lipidomics technologies, focusing on their applications in cancer research.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    URL: Article
    DOI: 10.3390/cancers13030474
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2527080-1
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  • 7
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    Lipid Metabolic Reprogramming in Hepatocellular Carcinoma
    MDPI AG ; 2018
    In:  Cancers Vol. 10, No. 11 ( 2018-11-15), p. 447-
    Details
    In: Cancers, MDPI AG, Vol. 10, No. 11 ( 2018-11-15), p. 447-
    Abstract: Metabolic reprogramming for adaptation to the local environment has been recognized as a hallmark of cancer. Although alterations in fatty acid (FA) metabolism in cancer cells have received less attention compared to other metabolic alterations such as glucose or glutamine metabolism, recent studies have uncovered the importance of lipid metabolic reprogramming in carcinogenesis. Obesity and nonalcoholic steatohepatitis (NASH) are well-known risk factors of hepatocellular carcinoma (HCC), and individuals with these conditions exhibit an increased intake of dietary FAs accompanied by enhanced lipolysis of visceral adipose tissue due to insulin resistance, resulting in enormous exogenous FA supplies to hepatocytes via the portal vein and lymph vessels. This “lipid-rich condition” is highly characteristic of obesity- and NASH-driven HCC. Although the way in which HCC cells adapt to such a condition and exploit it to aid their progression is not understood, we recently obtained new insights into this mechanism through lipid metabolic reprogramming. In addition, accumulating evidence supports the importance of lipid metabolic reprogramming in various situations of hepatocarcinogenesis. Thus, in this review, we discuss the latest findings regarding the role of FA metabolism pathways in hepatocarcinogenesis, focusing on obesity- and NASH-driven lipid metabolic reprogramming.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    URL: Article
    DOI: 10.3390/cancers10110447
    Language: English
    Publisher: MDPI AG
    Publication Date: 2018
    detail.hit.zdb_id: 2527080-1
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  • 8
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    Peribiliary Glands as the Cellular Origin of Biliary Tract Cancer
    MDPI AG ; 2018
    In:  International Journal of Molecular Sciences Vol. 19, No. 6 ( 2018-06-12), p. 1745-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 19, No. 6 ( 2018-06-12), p. 1745-
    Type of Medium: Online Resource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms19061745
    Language: English
    Publisher: MDPI AG
    Publication Date: 2018
    detail.hit.zdb_id: 2019364-6
    SSG: 12
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  • 9
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    Exposure to Heated Tobacco Products Aerosol Causes Acute Stress Responses in the Lung of Mouse
    MDPI AG ; 2022
    In:  Antioxidants Vol. 11, No. 12 ( 2022-11-25), p. 2329-
    Details
    In: Antioxidants, MDPI AG, Vol. 11, No. 12 ( 2022-11-25), p. 2329-
    Abstract: In the present study, we evaluated the acute response of mice exposed to IQOS aerosol, a brand-name heated tobacco product (HTP), in the lung tissue. First, the thiobarbituric acid-reactive substances (TBA-RS) value was measured as an index to assess oxidative stress, and a significant increase was observed after exposure, followed by a significant increase in the total lung GSH concentration. The stress responses induced by IQOS aerosols was then analyzed by focusing on the changes in Nrf2 and ATF4, which are transcription factors that induce the expression of genes involved in GSH biosynthesis or metabolism. Although Nrf2 activation was not observed, significant accumulation of ATF4 in the nuclear fraction was noted three hours after exposure to IQOS aerosols. Upon an examination of changes in factors in the GSH biosynthetic system, a significant increase in cystine concentration in the lung tissue was measured, and an increase in xCT expression level was observed in the cell membrane fraction three–six hours after IQOS exposure. Furthermore, characteristic changes in HO-1, a stress-response protein regulated by ATF4, was discovered six hours after IQOS exposure. Moreover, analysis of the upstream ATF4 regulatory system revealed that phosphorylation of eIF2α was enhanced in the lung cytoplasmic fraction three hours after exposure to IQOS aerosols. These findings suggest that ER stress might be induced as an early response to IQOS aerosol exposure, accompanied by the activation of the eIF2α-ATF4 axis. These intracellular changes have also been reported after exposure to combustible cigarette smoke. Thus, the acute response found in the lungs of mice in the present study demonstrate that the inhalation of aerosols from IQOS elicits a biological response similar to that of combustible cigarette smoke. In conclusion, our results provide evidence that the biological effects of HTPs, such as IQOS, cannot be ignored in the lungs.
    Type of Medium: Online Resource
    ISSN: 2076-3921
    URL: Article
    DOI: 10.3390/antiox11122329
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2704216-9
    SSG: 15,3
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  • 10
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    Role of Endoscopic Ultrasonography-Guided Fine Needle Aspiration/Biopsy in the Diagnosis of Autoimmune Pancreatitis
    MDPI AG ; 2020
    In:  Diagnostics Vol. 10, No. 11 ( 2020-11-15), p. 954-
    Details
    In: Diagnostics, MDPI AG, Vol. 10, No. 11 ( 2020-11-15), p. 954-
    Abstract: Type 1 autoimmune pancreatitis (AIP) is histologically characterized by lymphoplasmacytic sclerosing pancreatitis (LPSP). Recently, the diagnostic yield of endoscopic ultrasonography-guided fine needle aspiration/biopsy (EUS-FNA/B) for AIP has been reported. However, its role in the diagnostic flow of AIP is not fully elucidated. We retrospectively reviewed 53 consecutive patients who were suspected with AIP and underwent EUS-FNA/B. We evaluated the contribution of EUS-FNA/B to the diagnosis of AIP before considering response to steroid therapy among patients with diffuse enlargement of the pancreas and those with focal enlargement, respectively. Twenty-two patients showed diffuse pancreatic enlargement and 31 showed focal enlargement. The final diagnosis was definitive AIP in 32 patients, probable AIP in 2, possible AIP in 1, and mass-forming focal pancreatitis in 18. There was no change in diagnosis after EUS-FNA/B among patients with diffuse pancreatic enlargement, while diagnosis changed in 38.7% (12/31) among those with focal enlargement—there was a probable to definitive diagnosis in 4 patients, unspecified to definitive in 3, and unspecified to probable in 5. EUS-FNB provided a significantly higher sensitivity for typical pathological findings of LPSP than EUS-FNA, and 10 patients were diagnosed as pathologically definitive AIP by EUS-FNB, though none were by EUS-FNA (p = 0.002). EUS-FNA/B was useful in the diagnosis of focal type AIP, and steroid therapy could be introduced after the diagnosis was confirmed. Meanwhile, EUS-FNA/B provided no contribution to diagnosis of diffuse type AIP. EUS-FNB showed a higher diagnostic yield than FNA.
    Type of Medium: Online Resource
    ISSN: 2075-4418
    URL: Article
    DOI: 10.3390/diagnostics10110954
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2662336-5
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