Frontiers in bioscience (Landmark edition)最新文献

{"title":"Decitabine Enhances Sorafenib Sensitivity in Renal Cell Carcinoma by Promoting BIN1 and SYNE1 Expressions.","authors":"Lijie Kang, Mengyun Jin, Yuqin Mao, Aixiao Xia","doi":"10.31083/j.fbl2910370","DOIUrl":"https://doi.org/10.31083/j.fbl2910370","url":null,"abstract":"<p><strong>Background: </strong>Renal cell carcinoma (RCC), especially clear cell RCC (ccRCC), significantly impacts health, and results in particularly poor outcomes in patients at the advanced stage. Resistance to vascular endothelial growth factor (VEGF) pathway-targeting tyrosine kinase inhibitors (TKIs) is a major barrier in effective ccRCC treatment. Herein, we aim to explore how decitabine mediates bridging integrator 1 (BIN1) and spectrin repeat containing nuclear envelope protein 1 (SYNE1) to impact resistance of ccRCC to sorafenib.</p><p><strong>Methods: </strong>Employing bioinformatics on datasets GSE64052 and CancerSea, we identified genes linked to TKI resistance, ultimately focusing on SYNE1. We assessed influences of SYNE1 overexpression and BIN1 knockdown via quantitative real-time PCR (qRT-PCR) and Western blot. Assessment of cell viability and apoptosis was accomplished using cell counting kit-8 (CCK-8) assays and flow cytometry. The investigation into the potential interactions between SYNE1 and BIN1, as well as their impacts on sorafenib sensitivity was accomplished by Co-Immunoprecipitation (Co-IP) and Glutathione-S-transferase (GST) Pull-down.</p><p><strong>Results: </strong>SYNE1 was substantially down-regulated in sorafenib-resistant ccRCC cells, and its overexpression increased sorafenib sensitivity, decreased viability and enhanced apoptosis. Interaction between BIN1 and SYNE1 was confirmed, with BIN1 level lower in resistant cells. BIN1 knockdown reduced the beneficial effects of SYNE1 overexpression on sorafenib sensitivity. Decitabine treatment elevated both SYNE1 and BIN1, while boosting apoptosis and reducing sorafenib resistance.</p><p><strong>Conclusions: </strong>SYNE1 contributes to the modulation of sorafenib resistance in ccRCC cells through interacting with BIN1. Decitabine treatment enhances expressions of these two proteins to improve TKI response, suggesting a potential strategy for counteracting resistance and bettering patient outcomes.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142549321","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":"Diallyl Disulfide Mitigates Cadmium Hepatotoxicity by Attenuating Oxidative Stress and TLR-4/NF-κB Signaling and Upregulating PPARγ.","authors":"Reem S Alruhaimi, Emad H M Hassanein, Mohammed F Alotaibi, Mohammed A Alzoghaibi, Omnia A M Abd El-Ghafar, Mostafa K Mohammad, Sulaiman M Alnasser, Ayman M Mahmoud","doi":"10.31083/j.fbl2910369","DOIUrl":"https://doi.org/10.31083/j.fbl2910369","url":null,"abstract":"<p><strong>Background: </strong>Heavy metals can cause serious health problems that affect different organs. Cadmium (Cd) is an environmental contaminant known for its toxicological consequences on different organs. Hepatotoxicity is a serious effect of exposure to Cd with oxidative stress (OS) and inflammation playing a central role. Diallyl disulfide (DADS), an organo-sulfur compound found in garlic, is known for its cytoprotective and antioxidant effects. In this study, the effect of DADS on Cd-induced inflammation, oxidative stress and liver injury was investigated.</p><p><strong>Methods: </strong>DADS was supplemented for 14 days via oral gavage, and a single intraperitoneal dose of Cd (1.2 mg/kg body weight) was administered to rats on day 7. Blood and liver samples were collected at the end of the experiment for analyses.</p><p><strong>Results: </strong>Cd administration resulted in remarkable hepatic dysfunction, degenerative changes, necrosis, infiltration of inflammatory cells, collagen deposition and other histopathological alterations. Cd increased liver malondialdehyde (MDA) and nitric oxide (NO) (<i>p</i> < 0.001), upregulated toll-like receptor (TLR)-4, nuclear factor-kappaB (NF-κB), pro-inflammatory mediators, and caspase-3 (<i>p</i> < 0.001) whereas decreased glutathione (GSH) and antioxidant enzymes (<i>p</i> < 0.001). Cd downregulated peroxisome proliferator activated receptor gamma (PPARγ), a transcription factor involved in inflammation and OS suppression (<i>p</i> < 0.001). DADS ameliorated liver injury and tissue alterations, attenuated OS and apoptosis, suppressed TLR-4/NF-κB signaling, and enhanced antioxidants. In addition, DADS upregulated PPARγ in the liver of Cd-administered rats.</p><p><strong>Conclusions: </strong>DADS is effective against Cd-induced hepatotoxicity and its beneficial effects are linked to suppression of inflammation, OS and apoptosis and upregulation of PPARγ. DADS could be valuable to protect the liver in individuals at risk of Cd exposure, pending further studies to elucidate other underlying mechanism(s).</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142549322","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":"Mitochondrial DNA Alterations in Glioblastoma and Current Therapeutic Targets.","authors":"Maher Kurdi, Ahmed Bamaga, Alaa Alkhotani, Thamer Alsharif, Ghada A Abdel-Hamid, Mohamed E Selim, Taghreed Alsinani, Ahmed Albeshri, Adnan Badahdah, Mazen Basheikh, Saleh Baeesa","doi":"10.31083/j.fbl2910367","DOIUrl":"https://doi.org/10.31083/j.fbl2910367","url":null,"abstract":"<p><p>Metabolic reprogramming within tumor cells involves a shift towards either glycolysis or mitochondrial respiration, depending on the stage of tumor progression. Consequently, irreversible dysfunction of the mitochondria is considered a crucial mechanism driving the progression mechanism. While numerous mutations in mitochondrial DNA (mtDNA) have been identified across various tumor types, including glioblastoma, many studies have been limited in the scope, focusing on small segments of mtDNA or utilizing sequencing methods with restricted sensitivity. As a result, several potentially significant mtDNA mutations may have been underestimated, along with their heteroplasmic states, which play a crucial role in determining the phenotypic impact of mtDNA mutation. Although both somatic and germline mtDNA mutations have been observed in different tumor types, research on the mtDNA mutations linked to glioblastoma remains scarce. The mitochondrial genome encodes thirteen protein-coding genes that are essential for the proper functioning of respiratory complex chains. Alterations in mitochondrial function manifest at various levels, including structural and functional changes, impacting mitogenic, hemodynamic, bioenergetic, and apoptotic signaling pathways. These alterations often signify a reduced efficiency of the oxidative phosphorylation system and energy production in tumor cells. As the crucial role of mitochondrial dysfunction in glioma development grows, mitochondria have emerged as promising targets for therapy aimed at overcoming chemoresistance and eliminating cancer cells. This brief review outlines the association between mtDNA alteration and glioblastoma, as well as the current advancements in therapeutic strategies targeting mtDNA alterations.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142549334","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":"Characterization of Extracellular Vesicles by Sulfophosphovanillin Colorimetric Assay and Raman Spectroscopy.","authors":"Alexey Senkovenko, Gleb Skryabin, Evgeniia Parshina, Alexey Piryazev, Elena Tchevkina, Dmitry Bagrov","doi":"10.31083/j.fbl2910366","DOIUrl":"https://doi.org/10.31083/j.fbl2910366","url":null,"abstract":"<p><strong>Background: </strong>Detailed characterization of extracellular vesicles (EVs) is crucial for their application in medical diagnostics. However, the complexity of their chemical composition and the heterogeneity of EV populations make their characterization challenging. Here we describe two analytical procedures that can help overcome this challenge.</p><p><strong>Methods: </strong>Small EVs were isolated from conditioned cell culture media using ultracentrifugation and characterized using nanoparticle tracking analysis (NTA) and transmission electron microscopy (TEM). Raman spectroscopy was used to assess the overall composition of the isolated samples and lipids extracted from them. Sulfophosphovanillin (SPV) colorimetric assay was used to quantify the contents of lipid.</p><p><strong>Results: </strong>Six samples of EVs were characterized. The lipid contents measured using SPV assay was in reasonable agreement with the quantitative estimates based on the particle size and concentration measured using NTA. The most peaks observed in the Raman spectra could be attributed to either proteins or lipids, and their origins was confirmed by lipid extraction. The protein-to-lipid ratio was estimated based on the Raman spectra.</p><p><strong>Conclusions: </strong>The experiential procedures described in this study will help to overcome the challenge of quick and highly informative characterization of the EVs.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142549319","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":"Estimation of Plasma Concentration of L-Carnosine and its Correlation with Core Symptoms of Autism Spectrum Disorder Children: A Pilot Clinical Trial.","authors":"Debi Ann Abraham, Udayakumar Narasimhan, Vijayakumar Thangavel Mahalingam, Manikandan Krishnan, Rajanandh Muhasaparur Ganesan, Khang Wen Goh, Ching Siang Tan, Long Chiau Ming, Chrismawan Ardianto","doi":"10.31083/j.fbl2910365","DOIUrl":"https://doi.org/10.31083/j.fbl2910365","url":null,"abstract":"<p><strong>Background: </strong>Literature indicates that L-carnosine may be deficient in autism spectrum disorder (ASD) children. The aim of the present study was to estimate the level of L-carnosine in plasma and correlate it with the Autism Treatment Evaluation Checklist (ATEC) and Childhood Autism Rating Scale 2nd Edition, Standard Version (CARS2-ST) scores. To measure L-carnosine level, a bio-analytical method was developed using reverse phase high- liquid chromatography and validated as per International Conference on Harmonization guidelines.</p><p><strong>Method: </strong>Children were supplemented with L-carnosine (10-15 mg/kg) along with standard care therapies for 2 months. Before and after supplementation, scores on the ATEC, CARS2-ST, BEARS sleep screening tool, 6-item Gastrointestinal Severity Index, and Parental Stress Scale were evaluated, and L-carnosine was measured at the end of the trial.</p><p><strong>Results: </strong>The calibration curve was linear in the range of 100-600 ng/mL (R² = 0.998). The level of L-carnosine quantified was 33.7 ± 0.2 ng/mL. There was no significant difference found in any of the outcome measures (<i>p</i> > 0.05).</p><p><strong>Conclusions: </strong>Despite the fact that L-carnosine is detectable in the blood, it was found to be ineffective in the management of ASD in children.</p><p><strong>Clinical trial registration: </strong>The study was registered in the Clinical Trial Registry-India, registration number: CTRI/2019/07/020102.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142549326","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":"Identification of Structure-Linked Activity on Bioactive Peptides from Sea Cucumber (<i>Stichopus japonicus</i>): A Compressive <i>In Silico/In Vitro</i> Study.","authors":"Hyo-Geun Lee, D P Nagahawatta, Jun-Geon Je, Jae-Young Oh, H H A C K Jayawardhana, N M Liyanage, M J M S Kurera, Si-Hyeong Park, You-Jin Jeon, Won-Kyo Jung, Yu Ri Choe, Hyun-Soo Kim","doi":"10.31083/j.fbl2910368","DOIUrl":"https://doi.org/10.31083/j.fbl2910368","url":null,"abstract":"<p><strong>Background: </strong>A sea cucumber (<i>Stichopus japonicus</i>) is an invertebrate rich in high-quality protein peptides that inhabits the coastal seas around East Asian countries. Such bioactive peptides can be utilized in targeted disease therapies and practical applications in the nutraceutical industry.</p><p><strong>Methods: </strong>Bioactive peptides were isolated from <i>Stichopus japonicus</i> through ultrafiltration and Sephadex G-10 size exclusion chromatography. The low-molecular-weight fraction (ACSH-III) showed the highest hydroxyl radical scavenging and angiotensin-converting enzyme (ACE) inhibitory activities. Subsequent purification of ACSH-III resulted in four fractions, of which ACSH-III-F3 and ACSH-III-F4 exhibited significant bioactivity.</p><p><strong>Results: </strong>Peptides identified in these fractions, including Phenylalanine-Proline-Threonine-Tyrosine (FPTY) and Tyrosine-Proline-Serine-Tyrosine-Proline-Serine (YPSYPS), were characterized using high-performance liquid chromatography (HPLC) and quadrupole time-of-flight mass spectrometry (QTOF-MS). FPTY demonstrated the most potent antioxidant and antihypertensive activities among these peptides, with IC₅₀ values of 0.11 ± 0.01 mg/mL for hydroxyl radicals and 0.03 ± 0.01 mg/mL for ACE inhibition. Docking simulations revealed strong binding affinities of these peptides to the active site of the ACE, with FPTY displaying interactions similar to those of the synthetic inhibitor lisinopril.</p><p><strong>Conclusions: </strong>These findings suggest that the identified peptides, particularly FPTY, have potential applications as natural antioxidants and functional foods.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142549331","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":"Formulating Spray-Dried Albumin-Modified Lipid Nanoparticles Encapsulating Acyclovir for Enhanced Pulmonary Drug Delivery.","authors":"Kewei Zhang, Zhen Han, Dagui Chen, Chenxi Zhang, Qian Zhang, Bo Cai, Yafei Qin, Kai Wang, Fusheng Shang, Jian Wan","doi":"10.31083/j.fbl2910363","DOIUrl":"https://doi.org/10.31083/j.fbl2910363","url":null,"abstract":"<p><strong>Background: </strong>Viral pneumonia, a pressing global health issue, necessitates innovative therapeutic approaches. Acyclovir, a potent ring-opening antiviral agent with broad-spectrum activity, faces water solubility, oral bioavailability, and drug resistance challenges. The aim of this study was to increase the efficacy of acyclovir through respiratory delivery by encapsulating it within albumin-modified lipid nanoparticles and formulate it as a spray.</p><p><strong>Methods: </strong>Nanoparticles was synthesized via the reverse evaporation method; its physicochemical characteristics were rigorously evaluated, including particle size, zeta potential, morphology, encapsulation efficiency, drug loading, and release profile. Furthermore, the cytotoxicity of nanoparticles and its therapeutic potential against viral pneumonia were assessed through cellular and animal model experiments. Result s: Nanoparticles exhibited a spherical morphology, with a mean particle size of 97.48 ± 5.36 nm and a zeta potential of 30.28 ± 4.72 mv; they demonstrated high encapsulation efficiency (93.26 ± 3.27%), drug loading (11.36 ± 0.48%), and a sustained release profile of up to 92% under neutral conditions. Notably, nanoparticles showed low cytotoxicity and efficient intracellular delivery of acyclovir. <i>In vitro</i> studies revealed that nanoparticles significantly reduced interleukin-6 levels induced by influenza virus stimulation. <i>In vivo</i>, nanoparticles treatment markedly decreased mortality, attenuated the inflammatory markers interleukin-6 and tumor necrosis factor-α levels, and mitigated inflammatory lung injury in mice with viral pneumonia.</p><p><strong>Conclusions: </strong>In this study, albumin was modified with polyethylene glycol (PEG) containing cationic lipid nanoparticles (LN) to prepare albumin-modified lipid nanoparticles encapsulating acyclovir (ALN-Acy), which can effectively deliver Acy into tissues and cells, prolong the survival of mice, and reduce lung injury and inflammatory factors. White albumin LN can be used as efficient drug delivery carriers, and the delivery of Acy via albumin LN is expected to be a therapeutic strategy for treating inflammatory diseases.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142549328","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":"A Dot-Blot Screening for Identifying the Temozolomide-Regulated Proteins as Potential Targets for Glioma Multi-OMICS Studies.","authors":"Anna Maria Bielecka-Wajdman, Grzegorz Machnik, Christina Linnebacher, Michael Linnebacher, Katarzyna Stec-Grosman, Ewa Obuchowicz","doi":"10.31083/j.fbl2910364","DOIUrl":"https://doi.org/10.31083/j.fbl2910364","url":null,"abstract":"<p><strong>Background: </strong>Malignant gliomas represent a heterogenous group of brain cancers that are characterized by infiltrative growth that lacks a clearly identifiable tumor border. The lack of the possibility of radical surgical resection and targeted therapy results in a poor prognosis. Although Temozolomide (TMZ) is still the leading chemotherapeutic agent in glioma treatment, its efficacy is limited due to the development of tumor resistance. Therefore, there an urgent need to improve the diagnosis and treatment of these tumors. Finding and developing biomarkers that are specific to glioma could be useful for both identifying therapy targets and monitoring treatment as well as for constructing a personalized therapy. However, there are still no reliable markers that would change the quality of glioma treatment.</p><p><strong>Methods: </strong>In this study, differences in the expression of 84 cancer-related proteins in three glioma cell lines were analyzed using the dot-blot method: commercial T98G cells and two patient-derived cell lines. The influence of TMZ on changes in protein expression, cell morphology, and migration was also investigated (Proteome Profiler Human XL Oncology Array, LeviCell System, Microscopic imaging). The lines that were analyzed were characterized by a remarkably different plasticity of protein expression and the proteomic alterations that were induced by TMZ.</p><p><strong>Results: </strong>A dot-blot analysis revealed ten proteins that were common to all of the lines and five (Cathepsin b, FGF, Survivin, AXL, Osteopontin) that were modulated by the TMZ. As a result of the exposure of TMZ, the proteins that are involved in chemoresistance and invasion (TIE-2, Thrombospondin) were detected in both the HROG02 and T98G cell lines. In the control culture (not exposed to TMZ) of HROG17 cells, the proteins that are involved in metabolism were strongly suppressed.</p><p><strong>Conclusions: </strong>The presented data sheds new light on the modulatory effect of Temozolomide on the expression of a protein panel: Cathepsin b, fibroblast growth factor (FGF), Survivin, AXL, and Osteopontin that may suggest their potential as therapeutic targets or biomarkers to monitoring therapy effects. However, further high-throughput analysis and detection of the proteins in the body fluids are necessary.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142549312","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":"GRK2 Protein Mediates the ANRIL, a lncRNA, to Affect the Proliferation and Apoptosis of Kasumi-1 Cells.","authors":"Siqi Wang, Chengsi Zhang, Huali Hu, Jianxia Xu, Jinxin Zhang, Wu Zhou, Fahua Deng, Yaming Zhang, Chenlong Hu, Yuancheng Liu, Hai Huang, Sixi Wei","doi":"10.31083/j.fbl2910362","DOIUrl":"https://doi.org/10.31083/j.fbl2910362","url":null,"abstract":"<p><strong>Background: </strong>A long non-coding RNAs (LncRNAs) called antisense noncoding RNA in the INK4 locus (<i>ANRIL</i>), has emerged as substantial regulators of cell survival in acute myeloid leukemia (AML). However, its speciffc and potential mechanism is uncertain in AML. In this research, we investigated the role of <i>ANRIL</i> in cell proliferation, apoptosis, and the underlying mechanism in AML cells.</p><p><strong>Methods: </strong><i>ANRIL</i> expression was quantified by real-time quantitative polymerase chain reaction (RT-qPCR). Kasumi-1 cells were transfected with LV-<i>ANRIL</i> plasmid to upregulate <i>ANRIL</i> expression, with or without co-transfection with a G Protein-Coupled Receptor Kinase 2 (GRK2) siRNA. Additionally, these cells were transfected with sh-<i>ANRIL</i> plasmid to inhibit <i>ANRIL</i> expression, with or without co-transfection with a GRK2 overexpression plasmid. Cell proliferation and apoptosis were determined using the cell counting kit-8 (CCK8) and flow cytometry. Protein expression levels of phosphatidylinositide 3-kinases (PI3K), protein kinase B (AKT), phosphorylated-Akt (p-AKT), Bcl-2-associated protein x (BAX), B-cell leukemia/lymphoma 2 protein (BCL-2), proliferating cell nuclear antigen (PCNA), cleaved caspase-3, and GRK2 were detected by western blot. The RNA-binding protein immunoprecipitation (RIP) assay was conducted to investigate the interaction between <i>ANRIL</i> and GRK2.</p><p><strong>Results: </strong><i>ANRIL</i> expression was increased in Kasumi-1 cells. <i>ANRIL</i> upregulation expression promoted cell proliferation and inhibited apoptosis. Furthermore, its upregulation led to increased expressions of PI3K, AKT, p-AKT, PCNA, and BCL-2, and decreased expression of BAX in Kasumi-1 cells. Additionally, transfection with GRK2 siRNA attenuated the promoting effect of LV-<i>ANRIL</i> on Kasumi-1 cells proliferation and the PI3K/AKT pathway, increased BAX and cleaved caspase-3 expressions, and decreased BCL-2 and PCNA expressions. GRK2 overexpression reversed the inhibitory effect of sh-<i>ANRIL</i> on cell proliferation and the PI3K/AKT pathway. Furthermore, it promoted BCL-2 and PCNA expressions, and inhibited BAX and cleaved caspase-3 expressions. RIP assay confirmed the physical interaction between <i>ANRIL</i> and GRK2.</p><p><strong>Conclusion: </strong>The GRK2 protein-mediated <i>ANRIL</i>, increasing Kasumi-1 cell proliferation and inhibiting apoptosis by activating the PI3K/AKT/BCL-2 pathway.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142549329","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":"Effect of Heat Stress on the Expression of Circulating Cyto(chemo)kine and Inflammatory Markers in Broiler Chickens Selected for High- or Low-water Efficiency.","authors":"Elizabeth S Greene, Travis Tabler, Walter G Bottje, Sara Orlowski, Sami Dridi","doi":"10.31083/j.fbl2910359","DOIUrl":"https://doi.org/10.31083/j.fbl2910359","url":null,"abstract":"<p><strong>Background: </strong>Water scarcity is a current, significant global concern that will only increase under the pressure of climate change. Improving water efficiency of poultry is a new and promising area to help temper agriculture's future impact on fresh water availability. Here, we explored the effects of acute heat stress (HS) on circulating stress and inflammatory markers in 2 lines of broilers divergently selected for water efficiency.</p><p><strong>Methods: </strong>Male chicks from low (LWE) and high water efficient (HWE) lines were raised in 12 environmental chambers (2 pens/chamber, 6 chambers/line, 20 birds/pen) under normal conditions until day 28. On day 29, birds were subjected to thermoneutral (TN, 25 °C) or HS (36 °C) conditions, resulting in four treatments (2 lines × 2 environmental conditions). After 3 h of HS, whole blood was collected (8 birds per line × environment) and analyzed for target gene expression and plasma cytokine levels. Data were analyzed by 2-way ANOVA, with line, environment, and their interaction as main factors, and means were compared using Tukey's multiple range test.</p><p><strong>Results: </strong>Gene expression of heat shock protein (HSP) 27, HSP70, interleukin (IL)-6, IL-18, c-reactive protein (CRP), tumor necrosis factor-α (TNFα), C-C motif chemokine ligand 4 (CCL4), CCL20, nucleotide-binding domain, leucine-rich repeat (NLR) family pyrin domain containing 3 (NLRP3), NLR family CARD domain containing 5 (NLRC5), and NLR family member X1 (NLRX1) were increased by HS, with no differences between the lines. HSP70, IL-10, and NLRC3 were lower in the HWE as compared to the LWE lines. Additionally, there were interactive effects between line and environment for HSP90, IL-4, and CCL4, where HS induced HSP90 expression in the LWE only, and IL-4 and CCL4 in HWE only. Arginine vasopressin (AVP) gene expression was significantly lower in the whole blood of the HWE line; however, plasma protein levels were not different.</p><p><strong>Conclusions: </strong>Overall, most of the effects seen on cyto (chemokines) and inflammatory markers were due to acute HS, with only a few genes differentially regulated between the lines. This likely indicates that the divergent selection for water efficiency for four generations did not elicit changes in inflammation and stress molecular signatures.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142549324","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}