Experimental biology and medicine (Maywood, N.J.)最新文献

{"title":"Iron-based phosphorus chelator: Risk of iron deposition and action on bone metabolism in uremic rats.","authors":"Wander Barros do Carmo,&nbsp;Bárbara Bruna Abreu Castro,&nbsp;Luísa Cardoso Manso,&nbsp;Priscylla Aparecida Vieira do Carmo,&nbsp;Clóvis Antônio Rodrigues,&nbsp;Melani Ribeiro Custódio,&nbsp;Vanda Jorgetti,&nbsp;Helady Sanders-Pinheiro","doi":"10.1177/15353702211057280","DOIUrl":"https://doi.org/10.1177/15353702211057280","url":null,"abstract":"<p><p>Phosphate chelators are frequently used in patients with chronic kidney disease (CKD). New iron-based chelators remain understudied and offer a promising therapeutic option for the control of bone and mineral disorders of chronic kidney disease (BMD-CKD). We assessed the effect of the phosphorus chelator, chitosan-iron III (CH-FeCl), compared to calcium carbonate (CaCO₃) in BMD-CKD and the potential iron overload in uremic rats. Thirty-two animals were divided into four groups, namely the control, CKD, CKD/CH-FeCl, and CKD/CaCO₃ groups. CKD was induced by adding 0.75% (4 weeks) and 0.1% (3 weeks) adenine to the diet. The chelators were administered from week 3 through week 7. The renal function, BMD-CKD markers, and histomorphometry of the femur were assessed at week 7. The CKD group showed a significant increase in creatinine (83.9 ± 18.6 vs. 41.5 ± 22.1 µmol/L; <i>P</i> = 0.001), phosphate (3.5 ± 0.8 vs. 2.2 ± 0.2 mmol/L; <i>P</i> = 0.001), fractional excretion of phosphorus (FEP) (0.71 ± 0.2 vs. 0.2 ± 0.17; <i>P</i> = 0.0001), and FGF23 (81.36 ± 37.16 pg/mL vs. 7.42 ± 1.96; <i>P</i> = 0.011) compared to the control group. There was no accumulation of serum or bone iron after the use of CH-FeCl. The use of chelators reduced the FEP (control: 0.71 ± 0.20; CKD/CH-FeCl: 0.40 ± 0.16; CKD/CaCO₃ 0.34 ± 0.15; <i>P</i> = 0.001), without changes in the serum FGF23 and parathyroid hormone levels. Histomorphometry revealed the presence of bone disease with high remodeling in the uremic animals without changes with the use of chelators. The CH-FeCl chelator was efficient in reducing the FEP without iron accumulation, thereby paving the way for the use of this class of chelators in clinical settings in the future.</p>","PeriodicalId":520623,"journal":{"name":"Experimental biology and medicine (Maywood, N.J.)","volume":" ","pages":"446-452"},"PeriodicalIF":3.2,"publicationDate":"2022-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8919316/pdf/10.1177_15353702211057280.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39688903","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Wnt signaling in biliary development, proliferation, and fibrosis.","authors":"Lipeng Tian,&nbsp;Yichen Wang,&nbsp;Yoon Young Jang","doi":"10.1177/15353702211061376","DOIUrl":"https://doi.org/10.1177/15353702211061376","url":null,"abstract":"<p><p>Biliary fibrosis is an important pathological indicator of hepatobiliary damage. Cholangiocyte is the key cell type involved in this process. To reveal the pathogenesis of biliary fibrosis, it is essential to understand the normal development as well as the aberrant generation and proliferation of cholangiocytes. Numerous reports suggest that the Wnt signaling pathway is implicated in the physiological and pathological processes of cholangiocyte development and ductular reaction. In this review, we summarize the effects of Wnt pathway in cholangiocyte development from embryonic stem cells, as well as the underlying mechanisms of cholangiocyte responses to adult ductal damage. Wnt signaling pathway is regulated in a step-wise manner during each of the liver differentiation stages from embryonic stem cells to functional mature cholangiocytes. With the modulation of Wnt pathway, cholangiocytes can also be generated from adult liver progenitor cells and mature hepatocytes to repair liver damage. Non-canonical Wnt signaling is triggered in the active ductal cells during biliary fibrosis. Targeted control of the Wnt signaling may hold the great potential to reduce and/or reverse the biliary fibrogenic process.</p>","PeriodicalId":520623,"journal":{"name":"Experimental biology and medicine (Maywood, N.J.)","volume":" ","pages":"360-367"},"PeriodicalIF":3.2,"publicationDate":"2022-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8899336/pdf/10.1177_15353702211061376.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39802199","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Innovative approaches for treatment of osteosarcoma.","authors":"Emel Rothzerg,&nbsp;Abigail L Pfaff,&nbsp;Sulev Koks","doi":"10.1177/15353702211067718","DOIUrl":"https://doi.org/10.1177/15353702211067718","url":null,"abstract":"<p><p>Osteosarcoma (OS) is the most common primary malignant bone tumor, which usually occurs in children and adolescents. It is generally a high-grade malignancy presenting with extreme metastases to the lungs or other bones. The etiology of the disease is multifaceted and still remains obscure. A combination of surgery and chemotherapy has played a major role in the treatment of OS over the past three decades, and consequently, the overall survival rates for the disease have remained unchanged. Therefore, there is an urgent need to employ new comprehensive analyses and technologies to develop significantly more informative classification systems, with the aim of developing more effective and less toxic therapies for OS patients. This review discusses the existing knowledge of OS therapy and potential methods to develop novel therapeutic agents for the disease.</p>","PeriodicalId":520623,"journal":{"name":"Experimental biology and medicine (Maywood, N.J.)","volume":" ","pages":"310-316"},"PeriodicalIF":3.2,"publicationDate":"2022-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8899335/pdf/10.1177_15353702211067718.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39830808","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Is COVID-19-associated cytokine storm distinct from non-COVID-19 secondary hemophagocytic lymphohistiocytosis?","authors":"Johnson M Liu,&nbsp;Jeffrey Chi","doi":"10.1177/15353702211068840","DOIUrl":"https://doi.org/10.1177/15353702211068840","url":null,"abstract":"<p><p>Cytokine storm is an umbrella term that describes an inflammatory syndrome characterized by elevated levels of circulating cytokines and hyperactivation of innate and/or adaptive immune cells. One type of cytokine storm is hemophagocytic lymphohistiocytosis (HLH), which can be either primary or secondary. Severe COVID-19-associated pneumonia and acute respiratory distress syndrome (ARDS) can also lead to cytokine storm/cytokine release syndrome (CS/CRS) and, more rarely, meet criteria for the diagnosis of secondary HLH. Here, we review the immunobiology of primary and secondary HLH and examine whether COVID-19-associated CS/CRS can be discriminated from non-COVID-19 secondary HLH. Finally, we review differences in immunobiology between these different entities, which may inform both clinical diagnosis and treatment of patients.</p>","PeriodicalId":520623,"journal":{"name":"Experimental biology and medicine (Maywood, N.J.)","volume":" ","pages":"330-337"},"PeriodicalIF":3.2,"publicationDate":"2022-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8899343/pdf/10.1177_15353702211068840.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39727714","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hyperinflammation after anti-SARS-CoV-2 mRNA/DNA vaccines successfully treated with anakinra: Case series and literature review.","authors":"Sara Bindoli,&nbsp;Alessandro Giollo,&nbsp;Paola Galozzi,&nbsp;Andrea Doria,&nbsp;Paolo Sfriso","doi":"10.1177/15353702211070290","DOIUrl":"https://doi.org/10.1177/15353702211070290","url":null,"abstract":"<p><p>The current SARS-CoV-2 pandemic diffused worldwide has encouraged the rapid development of vaccines to counter the spread of the virus. At present in Italy, 75.01% of the population completed the vaccination course (AIFA.gov.it) and very few adverse events have been recorded by now. Side-effects related to a theoretical over-reaction of the immune system in response to vaccines administration have been described, and the possibility that an autoimmune or a hyperinflammatory condition may occur was recently observed. Herein, we report four cases of hyperinflammatory syndrome with features indicative of Adult-onset Still's disease (AOSD) and macrophage activation syndrome (MAS), occurred after anti-SARS-CoV-2 vaccine injection and seen at our Unit between March and May 2021. Since interleukin (IL)-1 is one of the pivotal cytokines involved in AOSD pathogenesis, the inhibition of IL-1 is crucial in ameliorating the clinical symptoms of those patients. Moreover, it has been highlighted the central role of IL-1 as a hallmark of the hyperinflammatory status elicited by SARS-CoV-2 infection. In this case series, we successfully employed the IL-1 receptor antagonist anakinra to curb the cytokine release likely unleashed by the vaccine stimulation in potentially predisposed subjects. We also made a literature search to detect other patients with hyperinflammation temporally related to vaccines injection who benefited from IL-1 inhibition, while other AOSD/MAS-like described syndromes improved with other immunomodulatory strategies.</p>","PeriodicalId":520623,"journal":{"name":"Experimental biology and medicine (Maywood, N.J.)","volume":" ","pages":"338-344"},"PeriodicalIF":3.2,"publicationDate":"2022-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8899337/pdf/10.1177_15353702211070290.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39962553","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Galangin: A metabolite that suppresses anti-neoplastic activities through modulation of oncogenic targets.","authors":"Hardeep Singh Tuli,&nbsp;Katrin Sak,&nbsp;Shubham Adhikary,&nbsp;Ginpreet Kaur,&nbsp;Diwakar Aggarwal,&nbsp;Jagjit Kaur,&nbsp;Manoj Kumar,&nbsp;Nidarshana Chaturvedi Parashar,&nbsp;Gaurav Parashar,&nbsp;Uttam Sharma,&nbsp;Aklank Jain","doi":"10.1177/15353702211062510","DOIUrl":"https://doi.org/10.1177/15353702211062510","url":null,"abstract":"<p><p>With the dramatic increase in cancer incidence all over the world in the last decades, studies on identifying novel efficient anti-cancer agents have been intensified. Historically, natural products have represented one of the most important sources of new lead compounds with a wide range of biological activities. In this article, the multifaceted anti-cancer action of propolis-derived flavonoid, galangin, is presented, discussing its antioxidant, anti-inflammatory, antiproliferative, pro-apoptotic, anti-angiogenic, and anti-metastatic effects in various cancer cells. In addition, co-effects with standard chemotherapeutic drugs as well as other natural compounds are also under discussion, besides highlighting modern nanotechnological advancements for overcoming the low bioavailability issue characteristic of galangin. Although further studies are needed for confirming the anti-cancer potential of galangin <i>in vivo</i> malignant systems, exploring this natural compound might open new perspectives in molecular oncology.</p>","PeriodicalId":520623,"journal":{"name":"Experimental biology and medicine (Maywood, N.J.)","volume":" ","pages":"345-359"},"PeriodicalIF":3.2,"publicationDate":"2022-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8899339/pdf/10.1177_15353702211062510.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39812865","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Qualification of translational safety biomarkers.","authors":"John-Michael Sauer,&nbsp;Amy C Porter","doi":"10.1177/15353702211002153","DOIUrl":"https://doi.org/10.1177/15353702211002153","url":null,"abstract":"<p><p>Safety biomarkers are important drug development tools, both preclinically and clinically. It is a straightforward process to correlate the performance of nonclinical safety biomarkers with histopathology, and ideally, the biomarker is useful in all species commonly used in safety assessment. In clinical validation studies, where histopathology is not feasible, safety biomarkers are compared to the response of standard biomarkers and/or to clinical adjudication. Worldwide, regulatory agencies have put in place processes to qualify biomarkers to provide confidence in the manner of use and interpretation of biomarker data in drug development studies. This paper describes currently qualified safety biomarkers which can be utilized to monitor for nephrotoxicity and cardiotoxicity and ongoing projects to qualify safety biomarkers for liver, skeletal muscle, and vascular injury. In many cases, the development and use of these critical drug development tools is dependent upon partnerships and the precompetitive sharing of data to support qualification efforts.</p>","PeriodicalId":520623,"journal":{"name":"Experimental biology and medicine (Maywood, N.J.)","volume":" ","pages":"2391-2398"},"PeriodicalIF":3.2,"publicationDate":"2021-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/15353702211002153","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25509042","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Overcoming physiological barriers by nanoparticles for intravenous drug delivery to the lymph nodes.","authors":"Noah Trac,&nbsp;Eun Ji Chung","doi":"10.1177/15353702211010762","DOIUrl":"https://doi.org/10.1177/15353702211010762","url":null,"abstract":"<p><p>The lymph nodes are major sites of cancer metastasis and immune activity, and thus represent important clinical targets. Although not as well-studied compared to subcutaneous administration, intravenous drug delivery is advantageous for lymph node delivery as it is commonly practiced in the clinic and has the potential to deliver therapeutics systemically to all lymph nodes. However, rapid clearance by the mononuclear phagocyte system, tight junctions of the blood vascular endothelium, and the collagenous matrix of the interstitium can limit the efficiency of lymph node drug delivery, which has prompted research into the design of nanoparticle-based drug delivery systems. In this mini review, we describe the physiological and biological barriers to lymph node targeting, how they inform nanoparticle design, and discuss the future outlook of lymph node targeting.</p>","PeriodicalId":520623,"journal":{"name":"Experimental biology and medicine (Maywood, N.J.)","volume":" ","pages":"2358-2371"},"PeriodicalIF":3.2,"publicationDate":"2021-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/15353702211010762","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38957067","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Modeling adaptive drug resistance of colorectal cancer and therapeutic interventions with tumor spheroids.","authors":"Astha Lamichhane,&nbsp;Pradip Shahi Thakuri,&nbsp;Pouria Rafsanjani Nejad,&nbsp;Hossein Tavana","doi":"10.1177/15353702211014185","DOIUrl":"https://doi.org/10.1177/15353702211014185","url":null,"abstract":"<p><p>Drug resistance is a major barrier against successful treatments of cancer patients. Various intrinsic mechanisms and adaptive responses of tumor cells to cancer drugs often lead to failure of treatments and tumor relapse. Understanding mechanisms of cancer drug resistance is critical to develop effective treatments with sustained anti-tumor effects. Three-dimensional cultures of cancer cells known as spheroids present a biologically relevant model of avascular tumors and have been increasingly incorporated in tumor biology and cancer drug discovery studies. In this review, we discuss several recent studies from our group that utilized colorectal tumor spheroids to investigate responses of cancer cells to cytotoxic and molecularly targeted drugs and uncover mechanisms of drug resistance. We highlight our findings from both short-term, one-time treatments and long-term, cyclic treatments of tumor spheroids and discuss mechanisms of adaptation of cancer cells to the treatments. Guided by mechanisms of resistance, we demonstrate the feasibility of designing specific drug combinations to effectively block growth and resistance of cancer cells in spheroid cultures. Finally, we conclude with our perspectives on the utility of three-dimensional tumor models and their shortcomings and advantages for phenotypic and mechanistic studies of cancer drug resistance.</p>","PeriodicalId":520623,"journal":{"name":"Experimental biology and medicine (Maywood, N.J.)","volume":" ","pages":"2372-2380"},"PeriodicalIF":3.2,"publicationDate":"2021-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/15353702211014185","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39074984","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of calcium-sensing receptor signaling in regulating transepithelial calcium transport.","authors":"Rebecca Siu Ga Tan,&nbsp;Christy Hui Lin Lee,&nbsp;Henrik Dimke,&nbsp;R Todd Alexander","doi":"10.1177/15353702211010415","DOIUrl":"https://doi.org/10.1177/15353702211010415","url":null,"abstract":"<p><p>The calcium-sensing receptor (CaSR) plays a critical role in sensing extracellular calcium (Ca²⁺) and signaling to maintain Ca²⁺ homeostasis. In the parathyroid, the CaSR regulates secretion of parathyroid hormone, which functions to increase extracellular Ca²⁺ levels. The CaSR is also located in other organs imperative to Ca²⁺ homeostasis including the kidney and intestine, where it modulates Ca²⁺ reabsorption and absorption, respectively. In this review, we describe CaSR expression and its function in transepithelial Ca²⁺ transport in the kidney and intestine. Activation of the CaSR leads to G protein dependent and independent signaling cascades. The known CaSR signal transduction pathways involved in modulating paracellular and transcellular epithelial Ca²⁺ transport are discussed. Mutations in the CaSR cause a range of diseases that manifest in altered serum Ca²⁺ levels. Gain-of-function mutations in the CaSR result in autosomal dominant hypocalcemia type 1, while loss-of-function mutations cause familial hypocalciuric hypercalcemia. Additionally, the putative serine protease, FAM111A, is discussed as a potential regulator of the CaSR because mutations in FAM111A cause Kenny Caffey syndrome type 2, gracile bone dysplasia, and osteocraniostenosis, diseases that are characterized by hypocalcemia, hypoparathyroidism, and bony abnormalities, i.e. share phenotypic features of autosomal dominant hypocalcemia. Recent work has helped to elucidate the effect of CaSR signaling cascades on downstream proteins involved in Ca²⁺ transport across renal and intestinal epithelia; however, much remains to be discovered.</p>","PeriodicalId":520623,"journal":{"name":"Experimental biology and medicine (Maywood, N.J.)","volume":" ","pages":"2407-2419"},"PeriodicalIF":3.2,"publicationDate":"2021-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/15353702211010415","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38940551","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}