Cellular Physiology and Biochemistry最新文献

{"title":"Immunogenicity and Protection by DnaK and SpaA Recombinant Proteins Against <i>Erysipelothrix Rhusiopathiae</i> in a Murine Model.","authors":"Naiane Lima Godoy,&nbsp;Jonathan Ballico de Moraes,&nbsp;Cynthia Aparecida de Castro,&nbsp;Jhonne Pedro Pedott Santana,&nbsp;Teresa Cristina Zangirolami,&nbsp;Adilson José da Silva,&nbsp;Maria Teresa Marques Novo-Mansur,&nbsp;Fernanda de Freitas Anibal","doi":"10.33594/000000664","DOIUrl":"10.33594/000000664","url":null,"abstract":"<p><strong>Background/aims: </strong>Swine erysipelas is a disease caused by <i>Erysipelothrix rhusiopathiae</i>, a Gram-positive bacillus, which has great economic importance because it leads to the loss of the swine herd. To control this disease, animals are immunized with a cellular vaccine of killed or attenuated <i>E. rhusiopathiae</i>, but even with herd vaccination, cases of swine erysipelas outbreaks have been reported in the United States, China and Japan, leading to the search for other antigenic components of the bacteria that may promote greater protection against <i>E. rhusiopathiae</i>. The surface protein SpaA from <i>E. rhusiopathiae</i> has been shown to be a candidate to constitute a subunit vaccine, since it has already been reported to induce a host immune response against the bacterium. DnaK, a hsp70 molecular chaperone, also seems to be a good candidate in the composition of a vaccine, as it has been demonstrated to be an antigenic protein of the bacteria.</p><p><strong>Methods: </strong>This work evaluated the immunogenicity and protection induced by the <i>E. rhusiopathiae</i>e SpaA and DnaK recombinant proteins in a murine model, by intramuscular administration to mice with two doses of 100 µg at 21-day interval between them. The candidate proteins were tested either separately and together, compared with the commercial vaccine and the non-vaccination condition, and mice were challenged with a virulent strain of <i>E. rhusiopathiae</i>. Serum was collected to assess the produced antibodies and peripheral blood cells, whereas spleen and kidney tissues were assayed for <i>E. rhusiopathiae</i> presence by colony counting.</p><p><strong>Results: </strong>A survival curve of the animals was performed, which confirmed the protection induced by the proteins. IgG antibodies increased in the animal serum inoculated with the proteins when compared to the control, and a significant delay in disease symptoms was observed.</p><p><strong>Conclusion: </strong>These results suggest that <i>E. rhusiopathiae</i> DnaK and SpaA are immunogenic in mice and interfere with the disease development.</p>","PeriodicalId":9845,"journal":{"name":"Cellular Physiology and Biochemistry","volume":"57 5","pages":"379-394"},"PeriodicalIF":0.0,"publicationDate":"2023-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41182088","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Activity of Lysosomal ABCC3, ABCC5 and ABCC10 is Responsible for Lysosomal Sequestration of Doxorubicin and Paclitaxel-Oregongreen488 in Paclitaxel-Resistant Cancer Cell Lines.","authors":"Karolina Gronkowska,&nbsp;Sylwia Michlewska,&nbsp;Agnieszka Robaszkiewicz","doi":"10.33594/000000663","DOIUrl":"https://doi.org/10.33594/000000663","url":null,"abstract":"<p><strong>Background/aims: </strong>Cancer cell multidrug resistance induced by paclitaxel contributes to the high failure rates of chemotherapy and relapse of the disease. Several mechanisms have been described that underlie the observed resistance, including the overexpression of ABCB1 (P-glycoprotein), which represents an ATP-binding cassette (ABC) transmembrane protein, and its functional occurrence in lysosomal membranes is linked to drug accumulation in these organelles.</p><p><strong>Methods: </strong>Using clinically-relevant models of paclitaxel-resistant triple-negative breast cancer and non-small cell lung cancer cell lines, we provide evidence for the role of ABCC subfamily members in the lysosomal sequestration of drugs in multidrug resistant phenotypes. Proteins expression level and its cellular localisation was measured using Western Blot and confocal microscopy. Drug accumulation was analysed by confocal microscopy and flow cytometry. Drug cytotoxicity was tested using resasurin assay and anexin V propidium iodide staining.</p><p><strong>Results: </strong>Regardless of the alteration in gene expression, paclitaxel induced the intracellular redistribution of ABCC3, ABCC5 and ABCC10 and their enrichment in lysosomes. The use of ABCC inhibitors and transient silencing of these three genes limited the accumulation of doxorubicin and paclitaxel-OregonGreen488 in lysosomes, while having little impact on the total drug level inside cells. The cancer cells were also sensitized to various structurally unrelated chemotherapeutics of differing acidity.</p><p><strong>Conclusion: </strong>The results suggest that lysosome membranes anchored ABCC proteins which remained functionally active and were capable to load chemotherapeutics into lysosomes in paclitaxel-resistant cancer cells. Therefore, targeting of lysosomal ABCC transporters may help to overcome paclitaxel-induced resistance by reducing the accumulation of drugs in lysosomes.</p>","PeriodicalId":9845,"journal":{"name":"Cellular Physiology and Biochemistry","volume":"57 5","pages":"360-378"},"PeriodicalIF":0.0,"publicationDate":"2023-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41101324","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Induced Pluripotent Stem Cells (Ipscs) Based Liver Organoid: the Benefits and Challenges.","authors":"Wahyunia Likhayati Septiana,&nbsp;Ariyani Noviantari,&nbsp;Radiana Dhewayani Antarianto","doi":"10.33594/000000662","DOIUrl":"https://doi.org/10.33594/000000662","url":null,"abstract":"<p><p>The liver is the main metabolic organ and functions to regulate many physiological functions in the human body. Approximately 70% of liver mass consists of hepatic cells (hepatocytes), which execute the liver's metabolic processes. When liver damage progresses to a chronic condition, such as end-stage liver disease (ESLD) or cirrhosis of the liver, the patient's only option for therapy is organ transplantation if the supply of available transplanted organs is insufficient to meet the patient's needs. The fundamental objective of the search for alternatives to organ transplantation has been to make liver tissue replacement more accessible and to produce hepatic and bioartificial liver tissue. Multiple hepatic cell lineages can be formed from human-induced pluripotent stem cells (hiPSCs) from embryoid bodies to become mature hepatocytes. hiPSCs also show a promising source for manufacturing human liver spheroids and are made to produce three-dimensional hepatobiliary organoids, and in some ways, it also briefly highlights important features of early hepatogenesis. Unquestionably, the art of cell culture has evolved to include the use of organoid technology as a resource for learning human biology in the context of health and illness. Organoids are essentially miniature organs that can grow in a three-dimensional matrix to resemble genuine organs in terms of both structure and function. This review summarized alternative protocols to differentiate hepatocytes from iPSC and to produce liver organoids based on iPSC in various ways. The growth of human iPSCs into liver organoids has been accomplished using several procedures.</p>","PeriodicalId":9845,"journal":{"name":"Cellular Physiology and Biochemistry","volume":"57 5","pages":"345-359"},"PeriodicalIF":0.0,"publicationDate":"2023-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41116696","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tyrosine-Mutant AAV8 Vector Mediated Efficient and Safe Gene Transfer of Pigment Epithelium-Derived Factor to Mouse Lungs.","authors":"Débora P Ferreira,&nbsp;Sabrina V Martini,&nbsp;Helena A Oliveira,&nbsp;Adriana L Silva,&nbsp;Siddharth Shenoy,&nbsp;Daiqin Chen,&nbsp;Valentina Simon,&nbsp;Eric Han,&nbsp;Natalie E West,&nbsp;Jung Soo Suk,&nbsp;Patricia R M Rocco,&nbsp;Hilda Petrs-Silva,&nbsp;Marcelo M Morales,&nbsp;Fernanda F Cruz","doi":"10.33594/000000660","DOIUrl":"10.33594/000000660","url":null,"abstract":"<p><strong>Background/aims: </strong>Recombinant adeno-associated viruses (rAAV) are an important tool for lung targeted gene therapy. Substitution of tyrosine with phenylalanine residues (Y-F) in the capsid have been shown to protect the AAV vector from ubiquitin/proteasome degradation, increasing transduction efficiency. We tested the mutant Y733F-AAV8 vector for mucus diffusion, as well as the safety and efficacy of pigment epithelium-derived factor (PEDF) gene transfer to the lung.</p><p><strong>Methods: </strong>For this purpose, Y733F-AAV8-PEDF (10¹⁰ viral genome) was administered intratracheally to C57BL/6 mice. Lung mechanics, morphometry, and inflammation were evaluated 7, 14, 21, and 28 days after injection.</p><p><strong>Results: </strong>The tyrosine-mutant AAV8 vector was efficient at penetrating mucus in ex vivo assays and at transferring the gene to lung cells after in vivo instillation. Increased levels of transgene mRNA were observed 28 days after vector administration. Overexpression of PEDF did not affect in vivo lung parameters.</p><p><strong>Conclusion: </strong>These findings provide a basis for further development of Y733F-AAV8-based gene therapies for safe and effective delivery of PEDF, which has anti-angiogenic, anti-inflammatory and anti-fibrotic activities and might be a promising therapy for lung inflammatory disorders.</p>","PeriodicalId":9845,"journal":{"name":"Cellular Physiology and Biochemistry","volume":"57 5","pages":"331-344"},"PeriodicalIF":0.0,"publicationDate":"2023-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10313069","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"High Fat High Sugar Diet Reduces Small Intestinal Secretion by Sex-Dependent Mechanisms.","authors":"Kyle Miller,&nbsp;Sarah Carpinelli,&nbsp;Maxwell Rubin,&nbsp;John Ahlert,&nbsp;Aaron Kubinski,&nbsp;Brendan Van Iten,&nbsp;Kendra Sy,&nbsp;Bryan Lunt,&nbsp;Katerina Meassick,&nbsp;Stephen Ames,&nbsp;Emma Smith,&nbsp;Chaheyla R St Aubin,&nbsp;Layla Al-Nakkash","doi":"10.33594/000000659","DOIUrl":"https://doi.org/10.33594/000000659","url":null,"abstract":"<p><strong>Background/aims: </strong>The goal of this study was to determine the influence of high-fat high-sugar diet (Western diet) on intestinal function and subsequently to determine if there were any beneficial effects of exercise, genistein (a naturally occurring phytoestrogen) or both, on the intestine.</p><p><strong>Methods: </strong>We measured transepithelial short circuit current (I_sc), across freshly isolated segments of jejunum from male and female C57Bl/6J mice randomly assigned to one of the following groups for the 12-week study duration: high-fat high-sugar diet (HFS), HFS with genistein (Gen), HFS with exercise (Ex), or HFS with both genistein and exercise (Gen+Ex) and compared them to lean controls. Genistein concentration was 600 mg genistein/kg diet. Exercise comprised of moderate intensity treadmill running (150 min per week). At the completion of the study, segments of jejunum were frozen for western blot determination of key proteins involved in secretory and absorptive functions, as well as senescence. Intestinal morphology was assessed. Serum cytokine assays were performed.</p><p><strong>Results: </strong>Basal I_sc was significantly decreased (by 70%, P<0.05) in HFS females and males versus leans. This decrease was partially mitigated by exercise in both sexes. In females, the HFS-induced decrease in I_sc was attributed to a significant loss of CLC2, NKCC1 and CFTR expression whereas in males this was due to a significant loss of Na/K-ATPase, K_Ca and NKCC1 expression (indicating sex-dependent mechanisms). Exercise mitigated most of the loss of I_sc in both sexes. Our data suggested that A2BR levels were dysregulated in HFS fed mice and that concomitant treatment with Gen or Gen+Ex prevented this disruption in females only. Inflammatory state was associated with body weight changes.</p><p><strong>Conclusion: </strong>Our data suggests that the reduced basal jejunal I_sc in HFS mice is attributed to sex-dependent mechanisms and while exercise partially mitigated this, it's mechanism of action was unclear. Improved understanding of Western diet induced intestinal dysfunctions may allow for the development of novel drug targets to treat gastrointestinal disturbances in diabetic obesity.</p>","PeriodicalId":9845,"journal":{"name":"Cellular Physiology and Biochemistry","volume":"57 5","pages":"315-330"},"PeriodicalIF":0.0,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10150808","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Erratum.","authors":"","doi":"10.33594/000000644","DOIUrl":"https://doi.org/10.33594/000000644","url":null,"abstract":"","PeriodicalId":9845,"journal":{"name":"Cellular Physiology and Biochemistry","volume":"57 4","pages":"298"},"PeriodicalIF":0.0,"publicationDate":"2023-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10268342","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Erratum.","authors":"","doi":"10.33594/000000651","DOIUrl":"https://doi.org/10.33594/000000651","url":null,"abstract":"","PeriodicalId":9845,"journal":{"name":"Cellular Physiology and Biochemistry","volume":"57 4","pages":"306-307"},"PeriodicalIF":0.0,"publicationDate":"2023-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10268346","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Retraction Statement.","authors":"","doi":"10.33594/000000658","DOIUrl":"https://doi.org/10.33594/000000658","url":null,"abstract":"","PeriodicalId":9845,"journal":{"name":"Cellular Physiology and Biochemistry","volume":"57 4","pages":"314"},"PeriodicalIF":0.0,"publicationDate":"2023-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10268348","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Erratum.","authors":"","doi":"10.33594/000000648","DOIUrl":"https://doi.org/10.33594/000000648","url":null,"abstract":"","PeriodicalId":9845,"journal":{"name":"Cellular Physiology and Biochemistry","volume":"57 4","pages":"302"},"PeriodicalIF":0.0,"publicationDate":"2023-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10268337","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Retraction Statement.","authors":"","doi":"10.33594/000000655","DOIUrl":"https://doi.org/10.33594/000000655","url":null,"abstract":"","PeriodicalId":9845,"journal":{"name":"Cellular Physiology and Biochemistry","volume":"57 4","pages":"311"},"PeriodicalIF":0.0,"publicationDate":"2023-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10268338","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}