Experimental Biology and Medicine最新文献

{"title":"Creative and generative artificial intelligence for personalized medicine and healthcare: Hype, reality, or hyperreality?","authors":"Arash Shaban-Nejad, Martin Michalowski, Simone Bianco","doi":"10.1177/15353702241226801","DOIUrl":"10.1177/15353702241226801","url":null,"abstract":"","PeriodicalId":12163,"journal":{"name":"Experimental Biology and Medicine","volume":" ","pages":"2497-2499"},"PeriodicalIF":2.8,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10854468/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139680968","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"IP3R-1 aggravates endotoxin-induced acute lung injury in mice by regulating MAM formation and mitochondrial function.","authors":"Shuan Dong, Ya Wu, Yuan Zhang, Shaona Li, Qin Zhao, Shasha Liu, Yan Guo, Xiangyun Li, Kai Song, Lili Wu, Lina Wu, Jia Shi, Lirong Gong, Jianbo Yu","doi":"10.1177/15353702231220667","DOIUrl":"10.1177/15353702231220667","url":null,"abstract":"<p><p>Acute lung injury (ALI) caused by endotoxin represents one of the common clinical emergencies. Mitochondria-associated endoplasmic reticulum membranes (MAM) serve as a critical link between mitochondria and endoplasmic reticulum (ER), which has an essential effect on maintaining intracellular homeostasis. As an important component of MAM, type-1 inositol-1,4,5-trisphosphate receptor (IP3R-1) mediates the ER-to-mitochondrial transport of Ca²⁺. This study explored the role of IP3R-1 and MAM in ALI. Besides the levels of inflammasome-associated components interleukin (IL)-6, tumor necrosis factor (TNF)-α, and malonyldialdehyde (MDA) were increased in both bronchoalveolar lavage fluid (BALF) and serum, increased cross-sectional area of mitochondria, elevated MAM formation, and decreased respiratory control ratio (RCR) were observed within lung tissues collected in lipopolysaccharide (LPS)-treated mice, accompanied by upregulation of IP3R-1 in total lung lysates and MAM. Ca²⁺ uptake level in the mitochondria, production of reactive oxygen species (ROS) in the mitochondria, and the formation of MAM were elevated within LPS-treated MLE-12 cells, and all those changes in response to LPS were partly inhibited by knocking down of IP3R-1 expression in MLE-12 cells. Collectively, IP3R-1 has a critical effect on MAM formation and mitochondrial dysfunction, which could be innovative therapeutic targets for ALI caused by endotoxin.</p>","PeriodicalId":12163,"journal":{"name":"Experimental Biology and Medicine","volume":" ","pages":"2262-2272"},"PeriodicalIF":3.2,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10903239/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139073783","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Green synthesized silver nanoparticles for the treatment of diabetes and the related complications of hyperlipidemia and oxidative stress in diabetic rats.","authors":"Yousra G El-Baz, Amr Moustafa, Mohamed A Ali, Gaber E El-Desoky, Saikh M Wabaidur, Amjad Iqbal","doi":"10.1177/15353702231214258","DOIUrl":"10.1177/15353702231214258","url":null,"abstract":"<p><p>This study was conducted to compare the impact of cinnamon silver nanoparticles (C-Ag-NPs) and cinnamon aqueous extract (CAE) on the total body weight (TBW), body weight gain (BWG), blood count (BC), fasting blood glucose (FBG), triglycerides (TGs), total cholesterol (TC), low-density (LDL-C) and high-density (HDL-C) lipoprotein cholesterol, liver function enzymes, superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) of normal and streptozotocin (STZ) diabetic rats. The CAE was administered to rats at different doses (50.0 and 100.0 mg/kg bw), whereas the C-Ag-NPs were ingested at doses of 25.0 and 50.0 mg/kg bw for 30 days. At the end of the experiment, the administration of high or low dosages of CAE or C-Ag-NPs to diabetic rats significantly reduced the FBG, TC, TG, and LDL-C and significantly increased the HDL-C compared with the diabetic control rats. The highest dose (50.0 mg/kg bw) of the C-Ag-NPs was the most efficient at significantly reducing (<i>P</i> < 0.05) the levels of all the analyzed parameters compared with the CAE. However, the treated and normal rats did not show any hypoglycemic activity after ingesting the CAE or C-Ag-NPs. Such effects were associated with considerable increases in their BWG. The diabetic rats that ingested the CAE or C-Ag-NPs showed a gradual decrease in their FBG, TC, LDL, and TG levels, but they were still higher than those in the normal rats. Furthermore, the C-Ag-NPs and CAE considerably enhanced the hepatic (GPT, GOT, ALP, and GGT) and antioxidant biomarker enzyme activities (SOD, CAT, and GPx) in diabetic rats. Relative to the untreated diabetic control, the C-Ag-NPs were more effective than the CAE in the diabetic rats. The C-Ag-NPs exhibited a protective role against hyperglycemia and hyperlipidemia in the diabetic rats and modulated their liver function enzyme biomarkers and antioxidant enzyme activities more than the CAE.</p>","PeriodicalId":12163,"journal":{"name":"Experimental Biology and Medicine","volume":" ","pages":"2237-2248"},"PeriodicalIF":3.2,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10903233/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139416693","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dapagliflozin-entresto protected kidney from renal hypertension via downregulating cell-stress signaling and upregulating SIRT1/PGC-1α/Mfn2-medicated mitochondrial homeostasis.","authors":"Sheung-Fat Ko, Chih-Chao Yang, Pei-Hsun Sung, Ben-Chung Cheng, Pei-Lin Shao, Yi-Ling Chen, Hon-Kan Yip","doi":"10.1177/15353702231198087","DOIUrl":"10.1177/15353702231198087","url":null,"abstract":"<p><p>This study tested whether combined dapagliflozin and entresto would be superior to mere one therapy on protecting the residual renal function and integrity of kidney parenchyma in hypertensive kidney disease (HKD) rat. <i>In vitro</i> results showed that the protein expressions of oxidative-stress/mitochondrial-damaged (NOX-1/NOX-2/oxidized-protein/cytosolic-cytochrome-C)/apoptotic (mitochondrial-Bax/cleaved caspeases 3, 9)/cell-stress (p-ERK/p-JNK/p-p38) biomarkers were significantly increased in H₂O₂-treated NRK-52E cells than those of controls that were reversed by dapagliflozin or entresto treatment. Adult-male SD rats (<i>n</i> = 50) were equally categorized into group 1 (sham-operated-control), group 2 (HKD by 5/6 nephrectomy + DOCA-salt/25 mg/kg/subcutaneous injection/twice weekly), group 3 (HKD + dapagliflozin/orally, 20 mg/kg/day for 4 weeks since day 7 after HKD induction), group 4 (HKD + entresto/orally, 100 mg/kg/day for 4 weeks since day 7 after HKD induction), and group 5 (HKD + dapagliflozin + entresto/the procedure and treatment strategy were identical to groups 2/3/4). By day 35, circulatory levels of blood-urine-nitrogen (BUN)/creatinine and urine protein/creatinine ratio were lowest in group 1, highest in group 2, and significantly lower in group 5 than in groups 3/4, but no difference between groups 3/4. Histopathological findings showed the kidney injury score/fibrotic area/cellular expressions of oxidative-stress/kidney-injury-molecule (8-OHdG+/KIM-1+) exhibited an identical trend, whereas the cellular expressions of podocyte components (synaptopodin/ZO-1/E-cadherin) exhibited an opposite pattern of BUN level among the groups. The protein expressions of oxidative stress/mitochondrial-damaged (NOX-1/NOX-2/oxidized protein/cytosolic-cytochrome-C/cyclophilin-D)/apoptotic (mitochondrial-Bax/cleaved-caspase 3)/mitochondrial-fission (PINK1/Parkin/p-DRP1)/autophagic (LC3BII/LC3BI ratio, Atg5/beclin-1)/MAPK-family (p-ERK/p-JNK/p-p38) biomarkers displayed a similar pattern, whereas the protein expression of mitochondria-biogenesis signaling (SIRT1/PGC-1α-Mfn2/complex I-V) displayed an opposite pattern of BUN among the groups. In conclusion, combined dapagliflozin-entresto therapy offered additional benefits on protecting the residual kidney function and architectural integrity in HKD rat.</p>","PeriodicalId":12163,"journal":{"name":"Experimental Biology and Medicine","volume":" ","pages":"2421-2439"},"PeriodicalIF":3.2,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10903247/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138498196","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Radiogenomic landscape: Assessment of specific phagocytosis regulators in lower-grade gliomas.","authors":"Aierpati Maimaiti, Aimitaji Abulaiti, Bin Tang, Yilidanna Dilixiati, Xueqi Li, Suobinuer Yakufu, Yongxin Wang, Lei Jiang, Hua Shao","doi":"10.1177/15353702231211939","DOIUrl":"10.1177/15353702231211939","url":null,"abstract":"<p><p>Genome-wide CRISPR-Cas9 knockout screens have emerged as a powerful method for identifying key genes driving tumor growth. The aim of this study was to explore the phagocytosis regulators (PRs) specifically associated with lower-grade glioma (LGG) using the CRISPR-Cas9 screening database. Identifying these core PRs could lead to novel therapeutic targets and pave the way for a non-invasive radiogenomics approach to assess LGG patients' prognosis and treatment response. We selected 24 PRs that were overexpressed and lethal in LGG for analysis. The identified PR subtypes (PRsClusters, geneClusters, and PRs-score models) effectively predicted clinical outcomes in LGG patients. Immune response markers, such as CTLA4, were found to be significantly associated with PR-score. Nine radiogenomics models using various machine learning classifiers were constructed to uncover survival risk. The area under the curve (AUC) values for these models in the test and training datasets were 0.686 and 0.868, respectively. The CRISPR-Cas9 screen identified novel prognostic radiogenomics biomarkers that correlated well with the expression status of specific PR-related genes in LGG patients. These biomarkers successfully stratified patient survival outcomes and treatment response using The Cancer Genome Atlas (TCGA) database. This study has important implications for the development of precise clinical treatment strategies and holds promise for more accurate therapeutic approaches for LGG patients in the future.</p>","PeriodicalId":12163,"journal":{"name":"Experimental Biology and Medicine","volume":" ","pages":"2289-2303"},"PeriodicalIF":3.2,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10903236/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138801376","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Regulation of expression quantitative trait loci by SVA retrotransposons within the major histocompatibility complex.","authors":"Jerzy K Kulski, Abigail L Pfaff, Luke D Marney, Alexander Fröhlich, Vivien J Bubb, John P Quinn, Sulev Koks","doi":"10.1177/15353702231209411","DOIUrl":"10.1177/15353702231209411","url":null,"abstract":"<p><p>Genomic and transcriptomic studies of expression quantitative trait loci (eQTL) revealed that SINE-VNTR-Alu (SVA) retrotransposon insertion polymorphisms (RIPs) within human genomes markedly affect the co-expression of many coding and noncoding genes by coordinated regulatory processes. This study examined the polymorphic SVA modulation of gene co-expression within the major histocompatibility complex (MHC) genomic region where more than 160 coding genes are involved in innate and adaptive immunity. We characterized the modulation of SVA RIPs utilizing the genomic and transcriptomic sequencing data obtained from whole blood of 1266 individuals in the Parkinson's Progression Markers Initiative (PPMI) cohort that included an analysis of human leukocyte antigen (<i>HLA</i>)<i>-A</i> regulation in a subpopulation of the cohort. The regulatory properties of eight SVAs located within the class I and class II MHC regions were associated with differential co-expression of 71 different genes within and 75 genes outside the MHC region. Some of the same genes were affected by two or more different SVA. Five SVA are annotated in the human genomic reference sequence GRCh38.p14/hg38, whereas the other three were novel insertions within individuals. We also examined and found distinct structural effects (long and short variants and the CT internal variants) for one of the SVA (<i>R_SVA_24</i>) insertions on the differential expression of the <i>HLA-A</i> gene within a subpopulation (550 individuals) of the PPMI cohort. This is the first time that many HLA and non-HLA genes (multilocus expression units) and splicing mechanisms have been shown to be regulated by eight structurally polymorphic SVA within the MHC genomic region by applying precise statistical analysis of RNA data derived from the blood samples of a human cohort population. This study shows that SVA within the MHC region are important regulators or rheostats of gene co-expression that might have potential roles in diversity, health, and disease.</p>","PeriodicalId":12163,"journal":{"name":"Experimental Biology and Medicine","volume":" ","pages":"2304-2318"},"PeriodicalIF":3.2,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10903234/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138458874","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single-nucleotide polymorphisms of <i>TLR4</i> and <i>GAS7</i> linked to primary open-angle glaucoma among patients of Shenyang, China.","authors":"Jiao Jie, Tengfei Wu","doi":"10.1177/15353702231214254","DOIUrl":"10.1177/15353702231214254","url":null,"abstract":"<p><p>The potential for adverse outcomes and classifications of glaucoma differ among race, country, gender, and family medical history. Nearly, 50 represent candidate genes are considered as potential contributors to the happening for the primary open-angle glaucoma (POAG) since the advent of GWASs. Our investigation is the first to report the Toll-like receptor 4 (<i>TLR4</i>) and growth arrest-specific 7 (<i>GAS7</i>) among people in Shenyang, China; to investigate whether single-nucleotide polymorphisms (SNPs) in (<i>TLR4</i>) or <i>GAS7</i> gene are risk factors for POAG among people in Shenyang, China; and also to explore their potential pathogenic mechanisms. POAG patients from July 2015 to June 2019 at Shenyang Fourth People's Hospital were selected. A total of 218 POAG patients and 252 controls were enrolled. Eight potentially functional SNPs of <i>TLR4</i> (rs7868859, rs7873784, rs77358523, and rs752998) and <i>GAS7</i> (rs8012311, rs11656696, rs74629981, and rs9900085) were genotyped. Multifactor analysis was conducted to evaluate the correlation between <i>TLR4</i>, <i>GAS7</i>, and POAG. The allele frequency of rs7873784 of <i>TLR4</i> demonstrated that the GC (<i>P</i> = 0.030), CC (<i>P</i> = 0.040), and GC + CC genotypes (<i>P</i> = 0.009) were significantly higher compared with CC genotype for POAG patients than that for controls. The rs8072311 and rs9900085 of <i>GAS7</i> gene also were significantly associated with POAG. Haplotype analysis found that the C-A-T-A haplotype (order: rs7873784-rs77358523-rs752998-rs7868859) of <i>TLR4</i> gene and the two haplotypes A-C-C-A and C-C-A-C of <i>GAS7</i> (order: rs9900085-rs74629981-rs8072311-rs11656696) were associated with an elevated susceptibility to POAG (<i>P</i> < 0.05). In this study, rs7868859 of <i>TLR4</i> and rs8012311 and rs9900085 polymorphisms of <i>GAS7</i> were first identified to be related to POAG among people in Shenyang, China.</p>","PeriodicalId":12163,"journal":{"name":"Experimental Biology and Medicine","volume":" ","pages":"2319-2324"},"PeriodicalIF":3.2,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10903258/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139490893","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"EXPRESSION OF CONCERN: Diabetic human adipose tissue-derived mesenchymal stem cells fail to differentiate in functional adipocytes.","authors":"","doi":"10.1177/15353702231159815","DOIUrl":"10.1177/15353702231159815","url":null,"abstract":"","PeriodicalId":12163,"journal":{"name":"Experimental Biology and Medicine","volume":" ","pages":"2495"},"PeriodicalIF":3.2,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10903251/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10783493","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to \"CTRP3 protects against uric acid-induced endothelial injury by inhibiting inflammation and oxidase stress in rats\".","authors":"","doi":"10.1177/15353702231223093","DOIUrl":"10.1177/15353702231223093","url":null,"abstract":"","PeriodicalId":12163,"journal":{"name":"Experimental Biology and Medicine","volume":" ","pages":"2492"},"PeriodicalIF":3.2,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10903248/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139416692","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Quercetin suppresses ovariectomy-induced osteoporosis in rat mandibles by regulating autophagy and the NLRP3 pathway.","authors":"Yue Xiong, Cheng-Wei Huang, Chao Shi, Liang Peng, Yu-Ting Cheng, Wei Hong, Jian Liao","doi":"10.1177/15353702231211977","DOIUrl":"10.1177/15353702231211977","url":null,"abstract":"<p><p>With the aging population and the popularity of implant prostheses, an increasing number of postmenopausal osteoporosis (PMOP) patients require implant restorations; however, poor bone condition affects the long-term stability of implant prostheses. This study aimed to investigate the therapeutic effect of quercetin (QR) compared with alendronate (ALN), the primary treatment for PMOP, on mandibular osteoporosis (OP) induced by ovariectomy (OVX) in female rats. Adult female rats were treated with QR (50 mg/kg/day), ALN (6.25 mg/kg/week) by gavage for 8 weeks, chloroquine (CQ, 10 mg/kg/twice a week), and cytokine release inhibitory drug 3 (MCC950, 10 mg/kg/three times a week) by intraperitoneal injection for 8 weeks after bilateral OVX. Blood samples were collected prior to euthanasia; the mandibles were harvested and subjected to micro-computed tomography (micro-CT) and pathological analysis. QR administration controlled weight gain and significantly improved the bone microstructure in OVX rats, increasing bone mass, and bone mineral density (BMD), reducing bone trabecular spacing, and decreasing osteoclast numbers. Western blotting, real-time quantitative PCR (RT-qPCR), and serum markers confirmed that QR inhibited interleukin- 1β (IL-1β) and interleukin-18 (IL-18) on the nucleotide-binding oligomerization domain (NOD)-like receptor (NLR) protein 3 (NLRP3) pathway thereby inhibiting osteoclast differentiation, immunofluorescence and western blotting also confirmed that QR inhibited autophagy in OVX rats and suppressed the number of tartrate-resistant acid phosphatase (TRAP)-stained positive osteoclasts. The findings suggest that QR may protect the bone structure and prevent bone loss in osteoporotic rats by inhibiting the NLRP3 pathway and autophagy in osteoclasts with comparable effects to ALN, thus QR may have the potential to be a promising alternative supplement for the preventive and therapeutic treatment of PMOP.</p>","PeriodicalId":12163,"journal":{"name":"Experimental Biology and Medicine","volume":" ","pages":"2363-2380"},"PeriodicalIF":3.2,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10903250/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139490885","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}