Biomedical Journal最新文献

{"title":"Comprehensive insight into the alterations in the gut microbiome and the intestinal barrier as a consequence of iron deficiency anaemia.","authors":"Ana Soriano-Lerma, María García-Burgos, Wiley Barton, María José M Alférez, Jorge Valentín Crespo-Pérez, Miguel Soriano, Inmaculada López-Aliaga, Paul D Cotter, José A García-Salcedo","doi":"10.1016/j.bj.2024.100701","DOIUrl":"https://doi.org/10.1016/j.bj.2024.100701","url":null,"abstract":"<p><strong>Background: </strong>Iron deficiency is the top leading cause of anaemia, whose treatment has been shown to deteriorate gut health. However, a comprehensive analysis of the intestinal barrier and the gut microbiome during IDA have not been performed to date. This study aims to delve further into the analysis of these two aspects, which will mean a step forward minimising the negative impact of iron supplements on intestinal health.</p><p><strong>Methods: </strong>IDA was experimentally induced in an animal model. Shotgun sequencing was used to analyse the gut microbiome in the colonic region, while the intestinal barrier was studied through histological analyses, mRNA sequencing (RNA-Seq), qPCR and immunofluorescence. Determinations of lipopolysaccharide (LPS) and bacteria-specific immunoglobulins were performed to assess microbial translocation.</p><p><strong>Results: </strong>Microbial metabolism in the colon shifted towards an increased production of certain amino acids, short chain fatty acids and nucleotides, with Clostridium species being enriched during IDA. Structural alterations of the colonic epithelium were shown by histological analysis. RNA-Seq revealed a downregulation of extracellular matrix-associated genes and proteins and an overall underdeveloped epithelium. Increased levels of serum LPS and an increased immune response against dysbiotic bacteria support an impairment in the integrity of the gut barrier during IDA.</p><p><strong>Conclusions: </strong>IDA negatively impacts the gut microbiome and the intestinal barrier, triggering an increased microbial translocation. This study emphasizes the deterioration of gut health during IDA and the fact that it should be addressed when treating the disease.</p>","PeriodicalId":8934,"journal":{"name":"Biomedical Journal","volume":null,"pages":null},"PeriodicalIF":5.5,"publicationDate":"2024-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139569146","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gut microbiota and clinical response to immune checkpoint inhibitor therapy in patients with advanced cancer","authors":"","doi":"10.1016/j.bj.2024.100698","DOIUrl":"10.1016/j.bj.2024.100698","url":null,"abstract":"<div><h3>Background</h3><p>There is currently no well-accepted consensus on the association between gut microbiota and the response to treatment of immune checkpoint inhibitors (ICIs) in patients with advanced cancer.</p></div><div><h3>Methods</h3><p>Fecal samples were collected before ICI treatment. Gut microbiota was analyzed using 16 S ribosomal RNA sequencing. We investigated the relationship between the α-diversity of fecal microbiota and patients’ clinical outcomes. Microbiota profiles from patients and healthy controls were determined. Pre-treatment serum was examined by cytokine array.</p></div><div><h3>Results</h3><p>We analyzed 74 patients, including 42 with melanoma, 8 with kidney cancer, 13 with lung cancer, and 11 with other cancers. Combination therapy of <em>anti</em>-PD1 and <em>anti</em>-CTLA-4 was used in 14 patients, and monotherapy in the rest. Clinical benefit was observed in 35 (47.3 %) cases, including 2 complete responses, 16 partial responses, and 17 stable diseases according to RECIST criteria. No significant difference in α-diversity was found between the benefiter and non-benefiter groups. However, patients with α-diversity within the range of our healthy control had a significantly longer median overall survival (18.9 months), compared to the abnormal group (8.2 months) (<em>p</em> = 0.041, hazard ratio = 0.546) for all patients. The microbiota composition of the benefiters was similar to that of healthy individuals. Furthermore, specific bacteria, such as <em>Prevotella copri</em> and <em>Faecalibacterium prausnitzii</em>, were associated with a favorable outcome. We also observed that serum IL-18 before treatment was significantly lower in the benefiters, compared to non-benefiters.</p></div><div><h3>Conclusions</h3><p>The α-diversity of gut microbiota is positively correlated with more prolonged overall survival in cancer patients following ICI therapy.</p></div>","PeriodicalId":8934,"journal":{"name":"Biomedical Journal","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2319417024000015/pdfft?md5=06962946a4c13b4e2c4a2f0a22540d06&pid=1-s2.0-S2319417024000015-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139555972","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Heart rate variability as a predictor of cognitive decline: A possible role for the Central Autonomic Network","authors":"Paola Nicolini,&nbsp;Tiziano Lucchi,&nbsp;Marco Vicenzi","doi":"10.1016/j.bj.2024.100700","DOIUrl":"10.1016/j.bj.2024.100700","url":null,"abstract":"","PeriodicalId":8934,"journal":{"name":"Biomedical Journal","volume":null,"pages":null},"PeriodicalIF":5.5,"publicationDate":"2024-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2319417024000039/pdfft?md5=a3427d4489f0e0349ee7cb01fcccf850&pid=1-s2.0-S2319417024000039-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139510013","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Senescence: No country for old cells","authors":"Jan Martel,&nbsp;David M. Ojcius,&nbsp;John D. Young","doi":"10.1016/j.bj.2023.100697","DOIUrl":"10.1016/j.bj.2023.100697","url":null,"abstract":"","PeriodicalId":8934,"journal":{"name":"Biomedical Journal","volume":null,"pages":null},"PeriodicalIF":5.5,"publicationDate":"2023-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2319417023001348/pdfft?md5=3cbeb1aa8e6e0edf2b0ab034e7b69bd7&pid=1-s2.0-S2319417023001348-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139062318","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inactivation of Ymr1, Sjl2/3 phosphatases promotes stress resistance and longevity in wild type and Ras2G19V yeast","authors":"M.G. Mirisola ,&nbsp;V.D. Longo","doi":"10.1016/j.bj.2023.100694","DOIUrl":"10.1016/j.bj.2023.100694","url":null,"abstract":"<div><p>In <em>Saccharomyces cerevisiae</em>, Ras (<u>RA</u>t <u>S</u>arcoma) activity plays a central role in mediating the effect of glucose in decreasing stress resistance and longevity, with constitutive Ras activation mutations promoting cell growth and oncogenesis. Here, we used transposon mutagenesis in yeast to identify suppressors of the constitutively active Ras2G19V, orthologue of the KRASG12C mammalian oncogene. We identified mutations in <em>YMR1</em> (<u>Y</u>east <u>M</u>yotubularin <u>R</u>elated), <em>SJL2</em> (<u>S</u>ynapto<u>J</u>anin-<u>L</u>ike) and <em>SJL3</em> phosphatases, which target phosphatidylinositol phosphates, as the most potent suppressors of constitutive active Ras, able to reverse its effect on stress sensitization and sufficient to extend longevity. In <em>sjl2</em> mutants, the staining of Ras-GTP switched from membrane-associated to a diffuse cytoplasmic staining, suggesting that it may block Ras activity by preventing its localization. Whereas expression of the Sjl2 PI 3,4,5 phosphatase mediated stress sensitization in both the Ras2G19V and wild type backgrounds, overexpression of the phosphatidylinositol 3 kinase VPS34 (<u>V</u>acuolar <u>P</u>rotein <u>S</u>orting), promoted heat shock sensitization only in the Ras2G19V background, suggesting a complex relationship between different phosphatidylinositol and stress resistance. These results provide potential targets to inhibit the growth of cancer cells with constitutive Ras activity and link the glucose-dependent yeast pro-aging Ras signaling pathway to the well-established pro-aging PI3K (<u>P</u>hospho<u>I</u>nositide <u>3</u>-<u>K</u>inase) pathway in worms and other species raising the possibility that the conserved longevity effect of mutations in the PI3K-AKT (<u>AK</u> strain <u>T</u>ransforming) pathway may involve inhibition of Ras signaling.</p></div>","PeriodicalId":8934,"journal":{"name":"Biomedical Journal","volume":null,"pages":null},"PeriodicalIF":5.5,"publicationDate":"2023-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2319417023001312/pdfft?md5=cfaaa5588d94b7cd3bcdcda8467dab0b&pid=1-s2.0-S2319417023001312-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139058145","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Symptom-correlated MiRNA signature as a potential biomarker for Kawasaki disease","authors":"","doi":"10.1016/j.bj.2023.100684","DOIUrl":"10.1016/j.bj.2023.100684","url":null,"abstract":"","PeriodicalId":8934,"journal":{"name":"Biomedical Journal","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2023-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S231941702300121X/pdfft?md5=b3fef34c06e66d2f9b7f36b8543b8a4b&pid=1-s2.0-S231941702300121X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138573423","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neural oscillatory markers of respiratory sensory gating in human cortices","authors":"","doi":"10.1016/j.bj.2023.100683","DOIUrl":"10.1016/j.bj.2023.100683","url":null,"abstract":"<div><h3>Background</h3><p>Human respiratory sensory gating is a neural process associated with inhibiting the cortical processing of repetitive respiratory mechanical stimuli. While this gating is typically examined in the time domain, the neural oscillatory dynamics, which could offer supplementary insights into respiratory sensory gating, remain unknown. The purpose of the present study was to investigate central neural gating of respiratory sensation using both time- and frequency-domain analyses.</p></div><div><h3>Methods</h3><p>A total of 37 healthy adults participated in this study. Two transient inspiratory occlusions were presented within one inspiration, while responses in the electroencephalogram (EEG) were recorded. N1 amplitudes and oscillatory activities to the first stimulus (S1) and the second stimulus (S2) were measured. The perceived level of breathlessness and level of unpleasantness elicited by the occlusions were measured after the experiment.</p></div><div><h3>Results</h3><p>As expected, the N1 peak amplitude to the S1 was significantly larger than to the S2. The averaged respiratory sensory gating S2/S1 ratio for the N1 peak amplitude was 0.71. For both the evoked- and induced-oscillations, time-frequency analysis showed higher theta activations in response to S1 relative to S2. A positive correlation was observed between the perceived unpleasantness and induced theta power.</p></div><div><h3>Conclusions</h3><p>Our results suggest that theta oscillations, evoked as well as induced, reflect the “gating” of respiratory sensation. Theta oscillation, particularly theta-induced power, may be indicative of the emotional processing of respiratory mechanosensation. The findings of this study serve as a foundation for future investigations into the underlying mechanisms of respiratory sensory gating, particularly in patient populations.</p></div>","PeriodicalId":8934,"journal":{"name":"Biomedical Journal","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2023-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2319417023001208/pdfft?md5=ca0d42eb3dbb27c857ce7fe6f5dbf062&pid=1-s2.0-S2319417023001208-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138573889","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interferon-alpha and MxA inhibit BK polyomavirus replication by interaction with polyomavirus large T antigen","authors":"","doi":"10.1016/j.bj.2023.100682","DOIUrl":"10.1016/j.bj.2023.100682","url":null,"abstract":"<div><h3>Introduction</h3><p>BK Polyomavirus (BKPyV) infection is a common complication in kidney transplant recipients and can result in poor outcomes and graft failure. Currently, there is no known effective antiviral agent. This study investigated the possible antiviral effects of Interferon alpha (IFNα) and its induced protein, MxA, against BKPyV.</p></div><div><h3>Methods</h3><p><em>In vitro</em> cell culture experiments were conducted using human primary renal proximal tubular epithelial cells (HRPTECs). We also did animal studies using Balb/c mice with unilateral kidney ischemic reperfusion injury.</p></div><div><h3>Results</h3><p>Our results demonstrated that IFNα effectively inhibited BKPyV <em>in vitro</em> and murine polyomavirus in animal models. Additionally, IFNα and MxA were found to suppress BKPyV TAg and VP1 production. Silencing MxA attenuated the antiviral efficacy of IFNα. We observed that MxA interacted with BKPyV TAg, causing it to remain in the cytosol and preventing its nuclear translocation. To determine MxA's essential domain for its antiviral activities, different mutant MxA constructs were generated. The MxA mutant K83A retained its interaction with BKPyV TAg, and its antiviral effects were intact. The MxA T103A mutant, on the other hand, abolished GTPase activity, lost its protein-protein interaction with BKPyV TAg, and lost its antiviral effect.</p></div><div><h3>Conclusion</h3><p>IFNα and its downstream protein, MxA, have potent antiviral properties against BKPyV. Furthermore, our findings indicate that the interaction between MxA and BKVPyV TAg plays a crucial role in determining the anti-BKPyV effects of MxA.</p></div>","PeriodicalId":8934,"journal":{"name":"Biomedical Journal","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2023-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2319417023001191/pdfft?md5=c0596c768a5a0eb83d1611fd50c559ee&pid=1-s2.0-S2319417023001191-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138552211","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Colonizing foreign terrain: Insights into bacterial enteropathogens","authors":"Aila Akosua Kattner","doi":"10.1016/j.bj.2023.100681","DOIUrl":"10.1016/j.bj.2023.100681","url":null,"abstract":"<div><p>In this present issue of the <em>Biomedical Journal</em> insights into pediatric campylobacteriosis are granted, and a potential path to developing a parenteral vaccine against enterotoxigenic <em>E. coli</em> is demonstrated. Additionally, a study shows how the use of extracorporeal shockwave therapy contributes to countering osteonecrosis of the femoral head. Furthermore, the relation between intimate partner violence and a saliva biomarker is explored. Finally, findings concerning the risk of dementia in patients with autonomic nervous system dysregulation are elucidated; and patterns of non-Alzheimer disease pathophysiology in individuals with depressive disorder are revealed.</p></div>","PeriodicalId":8934,"journal":{"name":"Biomedical Journal","volume":null,"pages":null},"PeriodicalIF":5.5,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S231941702300118X/pdfft?md5=82cc43ff8d35edb9837bc4cfabdfb7e4&pid=1-s2.0-S231941702300118X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138476702","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Autonomic modulation and the risk of dementia in a middle-aged cohort: A 17-year follow-up study","authors":"Yu-Tsung Chou ,&nbsp;Zih-Jie Sun ,&nbsp;Shih-Chieh Shao ,&nbsp;Yi-Ching Yang ,&nbsp;Feng-Hwa Lu ,&nbsp;Chih-Jen Chang ,&nbsp;Tzu-Chi Liao ,&nbsp;Chung-Yi Li ,&nbsp;Tony Hsiu-Hsi Chen ,&nbsp;Jin-Shang Wu ,&nbsp;Edward Chia-Cheng Lai","doi":"10.1016/j.bj.2022.12.004","DOIUrl":"10.1016/j.bj.2022.12.004","url":null,"abstract":"<div><h3>Background</h3><p>Altered autonomic modulation, measured by heart rate variability (HRV), has been found to be associated with dementia risk in the elderly. However, long-term follow-up study evaluating the association between autonomic modulation from middle-age and the incidence of dementia has been limited.</p></div><div><h3>Methods</h3><p>This retrospective cohort analyzed data from Taiwan's National Health Insurance Database covering the period from 2001 to 2017, with a linkage to citywide health examinations conducted by Tainan Metropolitan City, Taiwan. We included subjects aged 45–64 years. The mean follow-up period was 15.75 ± 3.40 years. The measurements of HRV included resting heart rate, high frequency (HF), low frequency (LF), standard deviation of normal-to-normal R–R intervals (SDNN), ratio between the 30th and 15th R–R interval after standing up from the supine position (30/15 ratio), ratio between the R–R intervals during expiration and inspiration, and the ratio between the high- and low-frequency components (LF/HF). The main study outcome was the incidence of dementia. We performed multivariable Cox proportional hazard regression models to compare the risk of dementia among different HRV subgroups.</p></div><div><h3>Results</h3><p>We included 565 participants with a mean age of 53 (SD: 6) years, of whom 44% were male. The risk of dementia was significantly increased in association with lower parasympathetic HRV modulation, including SDNN (HR: 3.23, 95% CI: 1.55–6.73) and 30/15 ratio (HR: 3.52, 95%CI: 1.67–7.42). Moreover, the risk of dementia was increased in subjects with higher LF/HF ratios (HR: 2.05, 95% CI: 1.12–3.72).</p></div><div><h3>Conclusions</h3><p>Lower parasympathetic activity and higher sympathetic-vagal imbalance in middle-age were associated with dementia risk.</p></div>","PeriodicalId":8934,"journal":{"name":"Biomedical Journal","volume":null,"pages":null},"PeriodicalIF":5.5,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S231941702200172X/pdfft?md5=cb91d85fed2212a0c56a5481ca9affb9&pid=1-s2.0-S231941702200172X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9170467","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}