International Journal of Experimental Pathology最新文献

{"title":"Histomorphometric analysis of excisional cutaneous wounds with different diameters in an animal model","authors":"Janiele Staianov,&nbsp;Jeiciele Mayara Rodrigues Struz,&nbsp;Rafaela Viana Vieira,&nbsp;Rafael Messias Luiz,&nbsp;Ana Carla Zarpelon-Schutz,&nbsp;Kádima Nayara Teixeira,&nbsp;Juliana Bernardi-Wenzel","doi":"10.1111/iep.12520","DOIUrl":"10.1111/iep.12520","url":null,"abstract":"<p>The skin wound model in rats is a fundamental stage in preclinical trials, but there is a lack of standardization in these trials regarding the initial wound area, making analysis and comparison between studies difficult. Therefore, this study evaluates the healing progression of excisional skin lesions of varying diameters in Wistar rats, aiming to identify the optimal wound size for monitoring treatment effects on wound healing. Excisions of 0.8, 1.5, 2.0 and 3.0 cm in diameter were made on the back of the animals. Thirty animals were used per treatment and evaluated on days 3, 7, 10, 14 and 21 after surgery. The lesions were cleaned daily with saline solution until they were completely closed. The 0.8 cm group showed complete repair on D14, while in the other groups, the wounds persisted until day 21, with a reddened surface and no complete epidermal coverage, but with greater keratinization and presence of appendages in the 1.5 cm lesions. Therefore, as a standardization model for creating skin wounds, we suggest using 1.5 or 2.0 cm excisions, considering that 0.8 cm wounds close very early and 3.0 cm wounds, although behaving similarly to 2.0 cm wounds, are more invasive for the animals. The 1.5 cm model proved to be suitable for closure within 21 days. When evaluating a product intended to accelerate wound healing, 2.0 cm lesions are recommended to assess the effectiveness of the treatment.</p>","PeriodicalId":14157,"journal":{"name":"International Journal of Experimental Pathology","volume":"105 6","pages":"235-245"},"PeriodicalIF":1.8,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142500432","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Determination of osteopontin in monitoring retinal damage in metabolic syndrome","authors":"Ramona D'Amico,&nbsp;Rosalba Siracusa,&nbsp;Marika Cordaro,&nbsp;Roberta Fusco,&nbsp;Livia Interdonato,&nbsp;Gianluca Antonio Franco,&nbsp;Salvatore Cuzzocrea,&nbsp;Rosanna Di Paola,&nbsp;Daniela Impellizzeri","doi":"10.1111/iep.12518","DOIUrl":"10.1111/iep.12518","url":null,"abstract":"<p>Metabolic syndrome (MetS) is becoming an increasing public health challenge. Many of the individual components of MetS are associated with ocular changes, but it is not yet clear what the association is. It is known that MetS can lead to diabetes and hence its consequences such as retinopathy. Osteopontin (OPN) is a phosphoglycoprotein that appears to be implicated in diabetic retinopathy. Given the involvement of OPN in retinal damage, the aim of this research was to evaluate OPN expression and its variation over time in a model of MetS induced by 30% fructose consumption for 1, 2 and 3 months. The weight of the animals and the consumption of food and fructose/water were evaluated during the experiment. The results showed a time-dependent increase in weight and liquid consumption in animals treated with fructose, while there was no significant difference in food consumption. Subsequently, the biochemical parameters confirmed that the animals treated with fructose, over time, underwent alterations like those found in patients with MetS. We then moved on to the evaluation of OPN and microglia. In both cases, we observed a time-dependent increase in OPN and Iba-1 in fructose consumption. Furthermore, the results showed a gradual loss of ZO-1 and occludin levels over time. Thus identification of OPN in patients with MetS could be used as an early marker of retinal damage, and this could help to prevent the complications related to the progression of this pathology.</p>","PeriodicalId":14157,"journal":{"name":"International Journal of Experimental Pathology","volume":"105 6","pages":"206-218"},"PeriodicalIF":1.8,"publicationDate":"2024-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/iep.12518","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142465352","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":"Enhanced hepatoprotective effects of empagliflozin and vitamin D dual therapy against metabolic dysfunction-associated steatohepatitis in mice by boosted modulation of metabolic, oxidative stress, and inflammatory pathways","authors":"Wesam F. Farrash,&nbsp;Shakir Idris,&nbsp;Mohamed E. Elzubier,&nbsp;Elshiekh B. A. Khidir,&nbsp;Akhmed Aslam,&nbsp;Abdulrahman Mujalli,&nbsp;Riyad A. Almaimani,&nbsp;Ahmad A. Obaid,&nbsp;Mahmoud Z. El-Readi,&nbsp;Mohammad A. Alobaidy,&nbsp;Afnan Salaka,&nbsp;Afnan M. Shakoori,&nbsp;Alaa M. Saleh,&nbsp;Faisal Minshawi,&nbsp;Jamil A. Samkari,&nbsp;Sallwa M. Alshehre,&nbsp;Bassem Refaat","doi":"10.1111/iep.12519","DOIUrl":"10.1111/iep.12519","url":null,"abstract":"<p>Although single treatment with sodium-glucose cotransporter-2 inhibitors (SGLT2i) or vitamin D₃ (VD₃) inhibited metabolic dysfunction-associated steatohepatitis (MASH) development in diabetic patients, their combination has not been explored previously. Hence, this study investigated the hepatoprotective effects of SGLT2i (empagliflozin) and/or VD₃ against MASH in type 2 diabetic mice. Forty Mice were assigned into negative (NC) and positive (PC) controls, SGLT2i, VD₃, and SGLT2i + VD₃ groups. All animals, except the NC group, received high-fructose/high-fat diet (8 weeks) followed by diabetes induction. Diabetic mice then received another cycle of high-fructose/high-fat diet (4 weeks) followed by 8 weeks of treatment (five times/week) with SGLT2i (5.1 mg/kg/day) and/or VD₃ (410 IU/Kg/day). The PC group demonstrated hyperglycaemia, dyslipidaemia, elevated liver enzymes, and increased non-alcoholic fatty liver disease activity score (NAS) with fibrosis. Hepatic glucose transporting molecule (SGLT2) with lipogenesis (SREBP-1/PPARγ), oxidative stress (MDA/H₂O₂), inflammation (IL1β/IL6/TNF-α), fibrosis (TGF-β1/α-SMA), and apoptosis (TUNEL/Caspase-3) markers alongside the PI3K/AKT/mTOR pathway increased in the PC group. Conversely, hepatic insulin-dependent glucose transporter (GLUT4), lipolytic (PPARα/INSIG1), antioxidant (GSH/GPx1/SOD1/CAT), and anti-inflammatory (IL-10) molecules with the inhibitor of PI3K/AKT/mTOR pathway (PTEN) decreased in the PC group. Whilst SGLT2i monotherapy outperformed VD₃, their combination showed the best attenuation of hyperglycaemia, dyslipidaemia, and fibrosis with the strongest modulation of hepatic glucose-transporting and lipid-regulatory molecules, PI3K/AKT/mTOR pathway, and markers of oxidative stress, inflammation, fibrosis, and apoptosis. This study is the first to reveal boosted hepatoprotection for SGLT2i and VD₃ co-therapy against diabetes-induced MASH, possibly via enhanced metabolic control and modulation of hepatic PI3K/AKT/mTOR, anti-inflammatory, anti-oxidative, and anti-fibrotic pathways.</p>","PeriodicalId":14157,"journal":{"name":"International Journal of Experimental Pathology","volume":"105 6","pages":"219-234"},"PeriodicalIF":1.8,"publicationDate":"2024-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142465353","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Thrombospondins: Conserved mediators and modulators of metazoan extracellular matrix","authors":"Josephine C. Adams","doi":"10.1111/iep.12517","DOIUrl":"10.1111/iep.12517","url":null,"abstract":"<p>This review provides a personal overview of significant scientific developments in the thrombospondin field during the course of my career. Thrombospondins are multidomain, multimeric, calcium-binding extracellular glycoproteins with context-specific roles in tissue organisation. They act at cell surfaces and within ECM to regulate cell phenotype and signalling, differentiation and assembly of collagenous ECM, along with tissue-specific roles in cartilage, angiogenesis and synaptic function. More recently, intracellular, homeostatic roles have also been identified. Resolution of structures for the major domains of mammalian thrombospondins has facilitated major advances in understanding thrombospondin biology from molecule to tissue; for example, in illuminating molecular consequences of disease-causing coding mutations in human pseudoachrondroplasia. Although principally studied in vertebrates, thrombospondins are amongst the most ancient of animal ECM proteins, with many invertebrates encoding a single thrombospondin and the thrombospondin gene family of vertebrates originating through gene duplications. Moreover, thrombospondins form one branch of a thrombospondin superfamily that debuted at the origin of metazoans. The super-family includes additional sub-groups, present only in invertebrates, that differ in N-terminal domain organisation, share the distinctive TSP C-terminal region domain architecture and, to the limited extent studied to date, apparently contribute to tissue development and organisation. Finally, major lines of translational research are discussed, related to fibrosis; TSP1, TSP2 and inhibition of angiogenesis; and the alleviation of chronic cartilage tissue pathologies in pseudoachrondroplasia.</p>","PeriodicalId":14157,"journal":{"name":"International Journal of Experimental Pathology","volume":"105 5","pages":"136-169"},"PeriodicalIF":1.8,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/iep.12517","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142255575","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":"Renal protective roles of macrophage matrix metalloproteinase-12 in mice with obstructed kidneys","authors":"Shunichiro Hanai,&nbsp;Daiki Nakagomi,&nbsp;Kotaro Suzuki,&nbsp;Hiroshi Nakajima,&nbsp;Fumihiko Furuya","doi":"10.1111/iep.12516","DOIUrl":"10.1111/iep.12516","url":null,"abstract":"<p>Matrix metalloproteinase (MMP)-12 has been reported to have diverse functions, including regulation of immune reactions and anti-inflammatory effects, but the potential roles of MMP-12 in kidney injury have not been fully elucidated. This study aimed to determine whether MMP-12 contributes to tubulointerstitial injury in a unilateral ureteric obstruction (UUO) model. MMP-12-deficient (MMP-12^−/−) mice and C57BL/6J mice as controls (MMP-12^+/+) were subjected to UUO and analysed 7 days after UUO. To analyse the functions of MMP-12 on monocytes/macrophages, we generated MMP-12-deficient, irradiated, chimeric mice (BM-MMP-12^−/−) and performed UUO. Bone marrow-derived macrophages (BMDMs) were isolated from both groups of mice and used for investigations. MMP-12^−/− mice showed exacerbation of macrophage accumulation and interstitial fibrosis in the UUO-kidney compared with control mice. BM-MMP-12^−/− mice also showed exacerbation of kidney injury. UUO induced accumulation of Ly6C⁺ macrophages in MMP-12^−/− mice compared with control mice. Increases in inflammatory cytokine (tumour necrosis factor α, interleukin [IL]-1β, IL-6) levels from BMDMs after lipopolysaccharide stimulation were higher in MMP-12^−/− mice than in MMP-12^+/+ mice. MMP-12 may play protective roles against kidney injury by UUO in mice, decreasing inflammatory cytokines from BMDMs and macrophage accumulation.</p>","PeriodicalId":14157,"journal":{"name":"International Journal of Experimental Pathology","volume":"105 5","pages":"193-201"},"PeriodicalIF":1.8,"publicationDate":"2024-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142008777","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Zinc transporter ZnT5 is associated with epithelial mesenchymal transition via SMAD1 in breast cancer","authors":"Erina Iwabuchi,&nbsp;Yasuhiro Miki,&nbsp;Junyao Xu,&nbsp;Ayako Kanai,&nbsp;Takanori Ishida,&nbsp;Hironobu Sasano,&nbsp;Takashi Suzuki","doi":"10.1111/iep.12515","DOIUrl":"10.1111/iep.12515","url":null,"abstract":"<p>Zinc levels in breast cancer tissues have been reported to be higher than those in normal tissues. In addition, the expression levels of zinc transporters, including ZnT5 and ZnT6, are reportedly higher in breast cancer than in normal breast tissues. ZnT5 and ZnT6 also contribute to heterodimer formation and are involved in several biological functions. However, the functions of ZnT5 and ZnT6 heterodimers in breast cancer remain unknown. Therefore, we first investigated the immunolocalization of ZnT5 and ZnT6 in pathological breast cancer specimens and in MCF-7 and T-47D breast cancer cells. Next, we used small interfering RNA to assess cell viability and migration in ZnT5 knockdown MCF-7 and T-47D cells. Immunohistochemical analysis showed that the number of ZnT5-positive breast cancer cells was inversely correlated with the pathologic N factor status. ZnT5 knockdown had no effect on cell viability in the presence of 100 μM ZnCl₂ in MCF-7 and T-47D cells. In a wound healing assay, 100 μM ZnCl₂ treatment inhibited cell migration of MCF-7 and T-47D cells, whereas ZnT5 knockdown promoted cell migration, decreased E-cadherin expression and increased vimentin, slug and matrix metalloproteinase 9 expression. Antibody arrays showed that ZnT5 knockdown increased the expression of SMAD1, and that dorsomorphin treatment inhibited the promotion of migratory ability induced by ZnT5 knockdown. The results of this study revealed that both ZnT5 may be involved in less aggressive breast cancer subtypes, possibly through inhibition of cell migration.</p>","PeriodicalId":14157,"journal":{"name":"International Journal of Experimental Pathology","volume":"105 5","pages":"184-192"},"PeriodicalIF":1.8,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/iep.12515","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141975585","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":"Feline hypertrophic cardiomyopathy: Does the microRNA-mRNA regulatory network contribute to heart sarcomeric protein remodelling?","authors":"Gabriella Guelfi,&nbsp;Noemi Venanzi,&nbsp;Camilla Capaccia,&nbsp;Valentina Stefanetti,&nbsp;Chiara Brachelente,&nbsp;Monica Sforna,&nbsp;Francesco Porciello,&nbsp;Elvio Lepri","doi":"10.1111/iep.12514","DOIUrl":"10.1111/iep.12514","url":null,"abstract":"<p>Feline primary hypertrophic cardiomyopathy (HCM) is an intrinsic myocardial disease characterized by concentric hypertrophy of the left ventricle. In the present study, we investigated the microRNA-mRNA regulatory network in feline myocardial tissue affected by primary (HCMI) and secondary HCM (HCMII). MRNA expression levels of sarcomeric genes, including, <i>TNNT2</i>, <i>TNNI3</i>, <i>MYH7</i>, <i>MYBPC3</i>, <i>TPM1</i> and <i>ACTC1</i> were assessed in the FFPE myocardial tissues. FFPE tissues from healthy cats were sequenced by the NGS, to explore, in the entire non-deposited miRNome, the expression level of microRNAs targeting the complementary sequences of selected sarcomeric mRNAs. The sarcomeric genes <i>TNNT2</i>, <i>MYH7</i>, <i>MYBPC3</i> and <i>TPM1</i> showed a statistically significant upregulation in HCMI compared to HCMII (<i>p</i> &lt; .01), except <i>ACTC1</i> which was downregulated (<i>p</i> &lt; .01); <i>TNNI3</i> showed no statistically significant difference. In HCMII miR-122-5p, miR-338-3p, miR-484, miR-370-3p, miR-92b-3p, miR-375 and miR-370-3p showed a significant upregulation (<i>p</i> &lt; .01) compared to control. The exception was miR-30a-5p which showed downregulation. Worthy of note is the 4-fold higher expression of miR-370-3p, a key regulator of <i>MYBPC3</i>, in HMCI compared to HMCII. This research does not solve the aetiological mystery of HCM, but it may help to find a way to help diagnose and define the prognosis of HCM in cats.</p>","PeriodicalId":14157,"journal":{"name":"International Journal of Experimental Pathology","volume":"105 5","pages":"170-183"},"PeriodicalIF":1.8,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/iep.12514","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141975584","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":"British Society for Matrix Biology Spring Meeting 2024: The Dynamic matrix—Mechanics, Ageing and Repair","authors":"","doi":"10.1111/iep.12512","DOIUrl":"10.1111/iep.12512","url":null,"abstract":"","PeriodicalId":14157,"journal":{"name":"International Journal of Experimental Pathology","volume":"105 4","pages":"A1-A23"},"PeriodicalIF":1.8,"publicationDate":"2024-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141748155","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"GABRP inhibits the progression of oesophageal cancer by regulating CFTR: Integrating bioinformatics analysis and experimental validation","authors":"Jingzhi Zhang,&nbsp;Xue Liu,&nbsp;Ling Zeng,&nbsp;Ying Hu","doi":"10.1111/iep.12513","DOIUrl":"10.1111/iep.12513","url":null,"abstract":"<p>Oesophageal cancer (EC) is a malignancy which accounts for a substantial number of cancer-related deaths worldwide. The molecular mechanisms underlying the pathogenesis of EC have not been fully elucidated. GSE17351 and GSE20347 data sets from the Gene Expression Omnibus (GEO) database were employed to screen differentially expressed genes (DEGs). Reverse transcription quantitative PCR (RT-qPCR) was used to examine hub gene expression. ECA-109 and TE-12 cells were transfected using the pcDNA3.1 expression vector encoding <i>GABRP</i>. The cell counting kit-8 (CCK-8), cell scratch and Transwell assays were performed to assess the effect of <i>GABRP</i> on EC cell proliferation, migration and invasion. Epithelial-mesenchymal transition (EMT)-associated protein levels were measured by Western blotting. Subsequently, <i>CFTR</i> was knocked down to verify whether <i>GABRP</i> affected biological events in EC cells by targeting <i>CFTR</i>. Seven hub genes were identified, including <i>GABRP</i>, <i>FLG</i>, <i>ENAH</i>, <i>KLF4</i>, <i>CD24</i>, <i>ABLIM3</i> and <i>ABLIM1</i>, which all could be used as diagnostic biomarkers for EC. The RT-qPCR results indicated that the expression levels of <i>GABRP</i>, <i>FLG</i>, <i>KLF4</i>, <i>CD24</i>, <i>ABLIM3</i> and <i>ABLIM1</i> were downregulated, whereas the expression level of <i>ENAH</i> was upregulated. In vitro functional assays demonstrated that <i>GABRP</i> overexpression suppressed the proliferation, migration, invasion and EMT of EC cells. Mechanistically, <i>GABRP</i> promoted the expression of <i>CFTR</i>, and <i>CFTR</i> knockdown significantly counteracted the influence of <i>GABRP</i> overexpression on biological events in EC cells. Overexpression of <i>GABRP</i> inhibited EC progression by increasing <i>CFTR</i> expression, which might be a new target for EC treatment.</p>","PeriodicalId":14157,"journal":{"name":"International Journal of Experimental Pathology","volume":"105 4","pages":"118-132"},"PeriodicalIF":1.8,"publicationDate":"2024-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141579639","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to “Clinical applications of gene therapy for rare diseases: A review”","authors":"","doi":"10.1111/iep.12505","DOIUrl":"10.1111/iep.12505","url":null,"abstract":"<p>Papaioannou I, Owen JS and Yáñez-Muñoz RJ. Clinical applications of gene therapy for rare diseases: A review. <i>Int J Exp Pathol</i> 2023 Aug;104(4):154–176. doi: 10.1111/iep.12478. Epub 2023 May 13.</p><p>It has been brought to our attention that in paragraph 1 of section 5.3, some details regarding the design of Zolgensma were not accurate. Therefore, the following text was incorrect: “Zolgensma (Onasemnogene Abeparvovec)^196–200 is an AAV-based gene supplementation treatment aimed at directly and permanently restoring <i>SMN1</i> expression with a single dose. The design of the Zolgensma expression cassette is similar to Luxturna (Figure 5), in using the hybrid CMV–Chicken beta actin promoter to drive the expression of <i>SMN1</i> cDNA. To enhance expression, the design incorporates an artificial intron (from SV40) and codon optimization. The sequence of AVXS-101 (the vector for Zolgensma) is proprietary and the exact optimizations are not in the public domain, but the effectiveness of this approach was documented by using a similar AAV9 platform.^201–203 A self-complementary design (Figure 12) was employed, where one of the flanking ITRs was a specially engineered variant to synthesize genome dimers, rather than monomers.²⁰⁴”</p><p>This should have read: “Zolgensma (Onasemnogene Abeparvovec)^196–200 is an AAV-based gene supplementation treatment aimed at directly and permanently restoring SMN protein production with a single dose. The design of the Zolgensma expression cassette is similar to Luxturna (Figure 5) in using the hybrid CMV–Chicken beta-actin promoter to drive the expression of <i>SMN2</i> cDNA, and it includes the bovine growth hormone polyadenylation sequence. To enhance expression, the design incorporates an artificial intron (from SV40). Unusually, the sequence of the <i>SMN2</i> cDNA in Zolgensma was not codon-optimized. The effectiveness of AVXS-101 (the vector for Zolgensma) was corroborated by the work of several other groups using similar self-complementary AAV9-<i>SMN</i> platforms^201–203 (Figure 12), where one of the flanking ITRs was a specially engineered variant to synthesize genome dimers, rather than monomers.²⁰⁴”</p><p>We apologize for this error.</p>","PeriodicalId":14157,"journal":{"name":"International Journal of Experimental Pathology","volume":"105 3","pages":"114"},"PeriodicalIF":3.0,"publicationDate":"2024-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/iep.12505","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140922113","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}