Histology and histopathology Vol.37, nº7 (2022)
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- PublicationOpen AccessNeuroprotective role of insulin-like growth factor 1 in auditory and other nervous systems(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2022) Yamahara, Kohei; Yamamoto, Norio; Kuwata, Fumihiko; Nakagawa, Takayukiy. Insulin-like growth factor 1 (IGF1) exerts an influence on almost every organ system in the body and plays an important role in growth, development, and metabolism. In the nervous system, IGF1 acts by promoting the development and growth of neurons and glial cells, differentiation of Schwann cells and their migration to axons, neurite outgrowth, and neuronal survival. The lack of IGF1 is associated with several pathological conditions, including severe prenatal growth retardation, postnatal growth failure, microcephaly, mental retardation, and bilateral sensorineural hearing loss. In addition to its physiological effects, based on the findings of in vivo and in vitro experiments and clinical trials, IGF1 is considered to play a potential role in the treatment of various types of neuronal damage. In this review, we discuss the potential use of IGF1 as a therapeutic molecule in the nervous system: (1) auditory system, including hair cells, cochlear ribbon synapses, auditory nerve, and central nervous systems, and (2) other peripheral nervous systems, especially the olfactory system and facial nerve. The role of IGF1 in the progression of age-related sensory deficits, especially hearing loss and olfactory dysfunction, is also discussed. Recent studies on IGF1 demonstrated that exogenous IGF1 can be applied in many fields, thus supporting the continued evaluation of IGF1 as a potential therapeutic molecule. Additional scientific investigations should be conducted to further supplement recent findings.
- PublicationOpen AccessThe clinicopathological and prognostic significances of LATS1 expression in breast cancer(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2022) Zheng, Hua Chuan; Xiang, Li Wei; Cui, Zheng Guo; Xue, Hang; E, Ying; Zhao, Ming ZhenAim. Large tumor suppressor gene 1 (LATS1) belongs to the PKA/PKG/PKC serine/threonine kinase subfamily of the Hippo signaling pathway and inactivates nuclear co-activators YAP1 and WWTR1 by phosphorylation. This study aimed to discern the clinicopathological and prognostic significances of LATS1 expression in breast cancer. Methods. We examined LATS1 expression in breast carcinogenesis and compared it with clinicopathological parameters and survival information of breast cancer patients using immunohistochemistry, western blotting, RT-PCR, and bioinformatics analysis. Results. LATS1 expression was downregulated in breast cancer at both mRNA and protein levels (P<0.05). LATS1 mRNA expression was negatively correlated with low ER and PR expression, aggressive subtypes (TNBC and HER2+ vs. luminal), and poor survival (P<0.05). Its protein expression was negatively linked to T stage, N stage, M stage, TNM stage, histological grade, PR status, and unfavorable prognosis (P<0.05). There was a positive correlationship between nuclar and cytoplasmic LATS1 expression in breast cancer (P<0.05). Conclusions. The downregulation of LATS1 expression plays a vital role in the carcinogenesis and progression of breast cancer. Thus, LATS1 loss was employed to indicate the aggressive behaviors and poor prognosis of breast cance
- PublicationOpen AccessHistological diversity of anti-PD1-induced colitis(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2022) Sakellariou, Stratigoula; Papathanasiou, Evgenia; Perdiki, Marina; Sotiropoulou, Maria; Zampeli, Evangelia; Michopoulos, Spyros; Bamias, Giorgos; Delladetsima, IoannaAim. Histological data on anti-PD1- associated colitis are limited, while the colitis subtypes are still not clearly defined and different terms are being used. The aim of the study was to explore the histopathology of anti-PD1-induced colitis. Methods and Results. Colonic biopsies from 9 patients under anti-PD1 agents presenting diarrhea were examined. Histological evaluation revealed colitis of mild to moderate severity in almost all cases. Four distinct dominant histological patterns were identified with nearly the same incidence: Ulcerative colitis (UC)- like (n=2), GVHD-like (n=2), collagenous-like (n=3) and a mixed colitis pattern combining features of microscopic and UC-like colitis (n=2). The latter was additionally characterized by high crypt epithelium apoptosis and cryptitis with mixed inflammatory infiltrate. Thickening of the subepithelial band of collagen, detachment of the surface epithelium and increased apoptosis of the crypt epithelium were commonly encountered features, irrespective of colitis subtype. CD4/CD8 ratio was lower in the “combined” and higher in the GVHD-like subtype. Conclusions. Anti-PD1-induced colitis is expressed by different patterns of injury which share distinct histological hallmarks harboring diagnostic value, while a “combined” colitis subtype is being established. The histological alterations are indicative of mucosa barrier damage after ant-PD1 treatment and its participation in the pathogenetic process
- PublicationOpen AccessClass II lupus nephritis with podocyte injury in imiquimod-induced lupus-prone mice(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2022) Murai, Atsuko; Yamazaki, Masaki; Kito, Aki; Nishihara, Kaori; Oyama, Sohei; Horiba, Naoshi; Kato, AtsuhikoLupus nephritis (LN) is a renal disease presented in systemic lupus erythematosus (SLE) and is divided into 6 classes based on histopathological criteria set by the International Society of Nephrology/Renal Pathology Society. Major mouse models of SLE usually develop class III/IV LN, which are characterized by subendothelial deposits and endocapillary hypercellularity. We examined the pathological features of kidneys in a mouse model of SLE induced by a tolllike receptor 7 agonist, imiquimod (IMQ). In experiment 1, eleven-female FVB/NJcl wild type mice were treated with IMQ on their ear skin 3 times per week. Plasma anti-dsDNA increased from 2 weeks after first IMQ treatment and 2 mice exhibited nephrotic syndrome from 6 weeks. Histopathology revealed eosinophilic mesangial deposits in all mice from 4 weeks. Subsequently, podocytes showed enlargement with vacuolation and their numbers decreased in 6 mice. There was no infiltration of inflammatory cells, subendothelial deposits in glomeruli, or subepithelial deposits in glomeruli. In experiment 2 using 10 mice at 8 weeks after IMQ treatment, the mesangial deposits were observed in all mice and confirmed to be IgG, IgA, IgM, C1q and C3 by immunofluorescence, which corresponds to class II LN. Foot process effacement was detected by transmission electron microscopy and was considered to lead to proteinuria. These mice exhibited pathological characteristics corresponding to class II LN and podocyte injury, which make it distinct from other mouse models of SLE
- PublicationOpen AccessThe expression of hydrogen sulfide-producing enzymes in primary and lung metastatic osteosarcoma(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2022) Gong, Lihua; Sun, Xiaoqi; Zhang, Ming; Du, Junbao; Ding, Yi; Jin, HongfangBackground. Hydrogen sulfide (H2S) is a novel gas transmitter signaling molecule. H2S is synthesized by cystathionine β-synthase (CBS), cystathionine γ-lyase (CSE), and 3-mercaptopyruvate sulfurtransferase (MST). There have been no reports about the roles of these enzymes in osteosarcoma and its metastases. We detected H2S synthase expression levels in human primary osteosarcoma and lung metastatic osteosarcoma. Methods. Immunohistochemistry was performed in primary osteosarcoma (n=19), lung metastatic osteosarcoma (n=11), osteoblastoma (n=10) and bony callus (n=2). The expression of CBS, CSE, and MST was defined as negative, moderately positive and strongly positive. Results. MST staining was moderately to strongly positive in all cases. CSE staining was negative in 94.7% (18/19) of primary osteosarcoma cases and 90.9% (10/11) of lung metastatic osteosarcoma cases. CBS staining was strongly positive in 68.4% (13/19) of primary osteosarcoma cases, moderately positive in 15.8% (3/19) of cases, and negative in 15.8% (3/19) of cases. In lung metastatic osteosarcoma, the proportions of negative, moderately positive and strongly positive cases were 63.6% (7/11), 18.2% (2/11) and 18.2% (2/11), respectively. Conclusions. CBS and CSE expression, especially CSE expression, decreased in both primary osteosarcoma and lung metastatic osteosarcoma, which may suggest that CBS and CSE play roles in osteoblast cell malignant transformation and osteosarcoma progression. These enzymes could be used as new prognostic assessment factors and may represent new therapeutic targets for osteosarcoma and metastasis prevention
- PublicationOpen AccessDepleting hsa_circ_0000567 suppresses acquired gefitinib resistance and proliferation of lung adenocarcinoma cells through regulating the miR-377-3p / ZFX axis: an in vitro and in vivo study(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2022) Wang, Lanjun; Li, Mengqi; Lian, RongBackground. Circular RNAs (circRNAs) expression profile has been reported in lung adenocarcinoma (LUAD) cells resistant to gefitinib, and hsa_circ_0000567 was abnormally upregulated. However, its precise role in gefitinib resistance remains unclarified. Methods. Levels of hsa_circ_0000567, microRNA (miR)-377-3p and zinc finger protein X-linked (ZFX) were detected by real-time quantitative PCR. Direct attachment was confirmed by dual-luciferase reporter assay and RNA immunoprecipitation assay. Gefitinib resistance was measured by MTT assay, colony formation assay, flow cytometry, western blotting, and xenograft in mice. Results. Expression of hsa_circ_0000567 was upreguated in human gefitinib-resistant human LUAD tissues and cells (HCC827/GR and PC9/GR). Clinically, higher hsa_circ_0000567 correlated with advanced tumor burden. Blockage of hsa_circ_0000567 suppressed cell viability, half maximal inhibitory concentration (IC50) value, colony formation ability, and expression of Bcl-2 and proliferating cell nuclear antigen (PCNA) in HCC827/GR and PC9/GR cells under gefitinib treatment or not, accompanied with enhanced apoptosis rate and Bax expression. In vivo, tumor growth of PC9/GR cells untreated and treated with gefitinib was restrained by silencing hsa_circ_0000567. miR-377-3p was directly regulated by hsa_circ_0000567, and then targeted ZFX. Similar to hsa_circ_0000567 knockdown, overexpressing miR377-3p inhibited chemoresistance in genitinib-resistant LUAD cells in vitro, whereas, depleting miR-377-3p was able to promote gefitinib resistance in spite of hsa_circ_0000567 knockdown. Moreover, restoring ZFX abrogated miR-377-3p-mediated chemosensitivity in genitinib-resistant LUAD cells in vitro. Conclusion. The hsa_circ_0000567/miR-377- 3p/ZFX axis might contribute to acquired gefitinib resistance in LUAD cells both in vitro and in vivo, suggesting hsa_circ_0000567 as a novel therapeutic target in treatment of gefitinib-resistant LUAD.
- PublicationOpen AccessThe PI3K/AKT signaling pathway: How does it regulate development of Sertoli cells and spermatogenic cells?(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2022) Chen, Kuang Qi; Wei, Bang Hong; Hao, Shuang Li; Yang, Wan XiThe PI3K/AKT signaling pathway is one of the most crucial regulatory mechanisms in animal cells, which can mainly regulate proliferation, survival and anti-apoptosis in cell lines. In the seminiferous epithelium, most studies were concentrated on the role of PI3K/AKT signaling in immature Sertoli cells (SCs) and spermatogonia stem cells (SSCs). PI3K/AKT signaling can facilitate the proliferation and antiapoptosis of immature Sertoli cells and spermatogenic cells. Besides, in mature Sertoli cells, this pathway can disintegrate the structure of the blood-testis barrier (BTB) via regulatory protein synthesis and the cytoskeleton of Sertoli cells. All of these effects can directly and indirectly maintain and promote spermatogenesis in male testis.
- PublicationOpen AccessThe clinicopathological and prognostic characteristics of mucinous micropapillary carcinoma of the breast(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2022) Sun, Yangyang; Gu, Wenxian; Wang, Gengfang; Zhou, XiaoliBackground. Mucinous micropapillary carcinoma (MMPC) is a unique subtype of breast cancer, and there is as yet no detailed report on the clinical characteristics of MMPC. Methods. MMPC, pure mucinous breast carcinoma (PMBC), and invasive micropapillary carcinoma (IMPC) samples were enrolled simultaneously, and immunohistochemistry analysis was performed to explore the clinicopathological attributes of MMPC. Moreover, survival analyses of MMPC were performed among the MMPC, PMBC, and IMPC groups and within the MMPC group. Results. The results showed that MMPC demonstrated distinct pathological features and that vascular invasion and lymph node metastasis were two significant clinical attributes of MMPC. MMPC leads to a shorter survival time than PMBC but an increased survival time compared to IMPC, while the tumor-nodemetastasis stage and lymph node metastasis were identified as two independent prognostic elements for disease-free survival in discerning the MMPC prognosis. Conclusions. The gathered data implied that further understanding and classification of MMPC may provide better individualized therapeutic strategies for MMPC treatment