Histology and histopathology Vol.38, nº9 (2023)
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- PublicationOpen AccessInduction of lncRNA MALAT1 by hypoxia promotes bone formation by regulating the miR-22-3p/CEBPD axis(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2023) Huang, Jiang; Shen, Hui liang; Feng, Ming-li; Li, Zheng; An, Shuai; Cao, Guang-leiAdaptation to hypoxia promotes fracture healing. However, the underlying molecular mechanism remains unknown. Increasing evidence has indicated that long non-coding RNAs (lncRNAs) play crucial roles in several diseases, including fracture healing. In the present study, lncRNA microarray analysis was performed to assess the expression levels of different lncRNAs in MC3T3-E1 cells cultured under hypoxic conditions. A total of 42 lncRNAs exhibited significant differences in their expression, including metastasis associated lung adenocarcinoma transcript 1 (MALAT1), maternally expressed 3, AK046686, AK033442, small nucleolar RNA host gene 2 and distal-less homeobox 1 splice variant 2. Furthermore, overexpression of MALAT1 promoted osteoblast differentiation, alkaline phosphatase (ALP) activity and matrix mineralization of MC3T3-E1 cells, whereas its knockdown diminished hypoxia-induced cell differentiation, ALP activity and matrix mineralization in these cells. Moreover, functional analysis indicated that MALAT1 regulated the mRNA and protein expression levels of CCAAT/ enhancer binding protein δ by competitively binding to microRNA-22-3p. Adenoviral-mediated MALAT1 knockdown inhibited fracture healing in a mouse model. Taken together, the results indicated that MALAT1 may serve a role in hypoxia-mediated osteogenesis and bone formation.
- PublicationOpen AccessMutant pattern of p53 predicts local recurrence and poor survival rate in gastric cancer(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2023) Chung, Yumin; Lee, Hyoun Wook; Park, Jung Ho; Yoo, Chang Hak; Son, Byung Ho; Kim, KyungeunBackground. TP53 mutation is a poor prognostic factor for various organ malignancies such as colorectal cancer, breast cancer, ovarian cancer, hepatocellular carcinoma, lung adenocarcinoma and clinical pathologists previously evaluated it using immunohistochemistry for p53. The clinicopathologic significance of p53 expression in gastric cancer remains unclear due to inconsistent classification methods. Methods. Immunohistochemistry for p53 protein was performed using tissue microarray blocks generated from 725 cases of gastric cancer, and p53 expression was divided into three staining patterns using a semiquantitative ternary classifier: heterogeneous (wild type), overexpression, and absence (mutant pattern). Results. Mutant pattern of p53 expression had a male predominance, greater frequency in cardia/fundus, higher pT stage, frequent lymph node metastasis, local recurrence clinically, and more differentiated histology microscopically compared with wild type. In survival analysis, p53 mutant pattern was associated with worse recurrent-free survival and overall survival rates, and significance was maintained in subgroup analysis of early versus advanced gastric cancers. In Cox regression analysis, p53 mutant pattern was a significant predicting factor for local recurrence (relative risk (RR=4.882, p<0.001)) and overall survival (RR=2.040, p=0.007). The p53 mutant pattern remained significant for local recurrence (RR=2.934, p=0.018) in multivariate analyses. Conclusions. Mutant p53 pattern on immunohistochemistry was a significant prognostic factor for local recurrence and poor overall survival in gastric cancer.
- PublicationOpen AccessDevelopment of a new treatment for preterm birth complications using amniotic fluid stem cell therapy(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2023) Abe, Yushi; Sato, Yu; Tanaka, Mamoru; Ochiai, DaigoThis paper describes the current status of studies and clinical trials on the use of mesenchymal stem cells (MSCs) and amniotic fluid stem cells (AFSCs) for complications of preterm birth (PTB), an urgent issue in the perinatal field. PTB is a serious challenge in clinical medicine that is increasing globally, and effective control of its complications is necessary for newborns’ subsequent long life. Classical treatments are inadequate, and many patients have PTB complications. A growing body of evidence provided by translational medicine and others indicates that MSCs, and among them, the readily available AFSCs, may be useful in treating PTB complications. AFSCs are the only MSCs available prenatally and are known to be highly antiinflammatory and tissue-protective and do not form tumors when transplanted. Furthermore, because they are derived from the amniotic fluid, a medical waste product, no ethical issues are involved. AFSCs are an ideal cell resource for MSC therapy in neonates. This paper targets the brain, lungs, and intestines, which are the vital organs most likely to be damaged by PTB complications. The evidence to date and future prospects with MSCs and AFSCs for these organs are described.
- PublicationOpen AccessCircRNA PDE3B regulates tumorigenicity via the miR-136-5p/MAP3K2 axis of esophageal squamous cell carcinoma(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2023) Yue, Wei; Ye, Yiwang; Chen, Baokun; Wu, Da; Wang, He; Hui, GangBackground. CircRNA has a covalently closed circular conformation and a stable structure. However, the exact role of circRNA in esophageal squamous cell carcinoma (ESCC) remains uncertain. The purpose of this study was to explore the role of hsa_circ_0000277 (circ_PDE3B) in ESCC. Methods. The expression levels of circ_PDE3B, miR-136-5p and mitogen-activated protein kinase kinase kinase 2 (MAP3K2) in ESCC tissues and cells were detected by quantitative real-time polymerase chain reaction (qRT-PCR) or western blot. The proliferation ability of EC9706 and KYSE30 cells was detected by clonal formation, 5-ethynyl-2’-deoxyuridine (EdU) and 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-Htetrazolium bromide (MTT) assays. Flow cytometry was used to detect the apoptosis rate of cells. Transwell assay was used to detect the invasion ability of EC9706 and KYSE3 cells. The relationship between miR-136-5p and circ_PDE3B or MAP3K2 was verified by dual-luciferase reporter assay and RNA pull-down, and the effect of circ_PDE3B on tumor growth in vivo was explored through tumor transplantation experiment. Immunohistochemistry (IHC) assay was used to detect MAP3K2 and Ki67 expression in mice tumor tissues. Results. The results showed that circ_PDE3B was highly expressed in ESCC tissues and cells. Downregulated circ_PDE3B expression in ESCC cells significantly reduced cell proliferation, migration and invasion. Circ_PDE3B served as a sponge for miR-136- 5p, and miR-136-5p inhibition reversed the roles of circ_PDE3B knockdown in ESCC cells. MAP3K2 was a direct target of miR-136-5p, and miR-136-5p targeted MAP3K2 to inhibit the malignant behaviors of ESCC cells. Furthermore, circ_PDE3B regulated MAP3K2 expression by sponging miR-136-5p. Importantly, circ_PDE3B knockdown inhibited tumor growth in vivo. Conclusions. In conclusion, circ_PDE3B acted as oncogenic circRNA in ESCC and accelerated ESCC progression by adsorption of miR-136-5p and activation of MAP3K2, supporting circ_PDE3B as a potential therapeutic target for ESCC.
- PublicationOpen AccessStructural and functional integrity of endocrine pancreas post administration of Karwinskia humboldtiana fruit to Wistar rats: a possible therapeutic application for cancer of exocrine origin(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2023) Segoviano Ramirez, Juan Carlos; Esparza Rodriguez, Nallely; Carcano Diaz, Katya; Diaz Perez, Rosa Nelly; Palma Nicolas, Jose Prisco; Hernandez Bello, Romel; García Juárez, JaimeAims. Pancreatic adenocarcinoma represents a therapeutic challenge due to the high toxicity of antineoplastic treatments and secondary effects of pancreatectomy. T-514, a toxin isolated from Karwinskia humboldtiana (Kh) has shown antineoplastic activity on cell lines. In acute intoxication with Kh, we reported apoptosis on the exocrine portion of pancreas. One of the mechanisms of antineoplastic agents is the induction of apoptosis, therefore our main objective was to evidence structural and functional integrity of the islets of Langerhans after the administration of Kh fruit in Wistar rats. Methods. TUNEL assay and immunolabelling against activated caspase-3 were used to detect apoptosis. Also, immunohistochemical tests were performed to search for glucagon and insulin. Serum amylase enzyme activity was also quantified as a molecular marker of pancreatic damage. Results. Evidence of toxicity on the exocrine portion, by positivity in the TUNEL assay and activated caspase-3, was found. On the contrary, the endocrine portion remained structurally and functionally intact, without apoptosis, and presenting positivity in the identification of glucagon and insulin. Conclusions. These results demonstrated that Kh fruit induces selective toxicity on the exocrine portion and establish a precedent to evaluate T-514 as a potential treatment against pancreatic adenocarcinoma without affecting the islets of Langerhans.
- PublicationOpen AccessLHPP promotes the intracellular reactive oxygen species accumulation and sensitivity of gastric cancer to cisplatin via JNK and p38 MAPK pathways(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2023) Gao, Kai; Yin, Ning; Shen, Zhaolong; Li, Qiqing; Chen, Peng; Yang, KaiyanBackground. Cisplatin is the first-line chemotherapy drug for the treatment of gastric cancer (GC) patients. However, GC patients who are resistant to cisplatin often do not benefit from it. Therefore, finding a key molecule that affects cisplatin sensitivity is expected to enhance the efficacy of cisplatin in GC treatment. Methods. The human GC cell lines SGC-7901 and BGC-823 were used. The protein chip array was used to screen the cisplatin-resistance genes from the complete response and non-complete response GC patients’ tissues, then, the differential gene expression analysis, GO function annotation analysis, and KEGG pathway enrichment analysis were performed. The GC tissue chip in the GEO database was analyzed to screen the target gene. Flow cytometry, Hoechst 33342 staining assay, Western Blot, MTT, tumor sphere formation, cell cycle, and apoptosis assays were performed to explore the effect of Phospholysine Phosphohistidine Inorganic Pyrophosphate Phosphatase (LHPP) on the apoptosis, stemness, and reactive oxygen species (ROS) accumulation of cisplatin-resistant GC cells treated with cisplatin. In vivo, the cisplatin-resistant GC cell lines transfected with pcDNA-LHPP or si-LHPP were injected subcutaneously into mice to construct GC subcutaneous xenograft GC models. Results. Based on protein chip array and bioinformatics analysis, it was found that LHPP is the core molecule in the cisplatin resistance regulatory network in GC, and its expression is down-regulated in GC cisplatin-resistant tissues and cells. In vitro and in vivo experimental results show that the up-regulated expression of LHPP is closely related to the increase in sensitivity of GC to cisplatin. Mechanically, we found that overexpression of LHPP may inhibit the activation of the JNK and p38 MAPK pathways, promote cisplatininduced ROS accumulation, suppress stemness, and enhance the sensitivity of GC to cisplatin. Conclusions. Up-regulation of LHPP may inhibit the activation of the JNK and p38 MAPK pathways, attenuate stemness, and enhance the accumulation of intracellular ROS, thereby promoting cisplatin-mediated GC cell apoptosis and enhancing cisplatin sensitivity.
- PublicationOpen AccessHsa_circ_0026344 suppresses gastric cancer progression via modulating the miR-1290/FBP2 axis(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2023) Xiao, GaoChun; Zhang, TingTing; Tan, BinBin; Hao, HuBackground. Circular RNAs (circRNAs) are a novel type of noncoding RNAs and play important roles in tumorigenesis, including gastric cancer (GC). However, the functions of most circRNAs remain poorly understood. In our study, we mainly learn the influence of hsa_circ_0026344 (circ_0026344) in GC progression. Methods. Circ_0026344, miR-1290 and Fructose1,6-bisphosphatase 2 (FBP2) expression was determined by quantitative real-time polymerase chain reaction (qRT-PCR). GC cell proliferation, migration, and invasion were detected by colony formation, 5-ethynyl2’-deoxyuridine (EdU), and transwell assays, respectively. The interaction between circ_0026344 and miR-1290 complex was evaluated by RNA pull-down assay. The interaction of miR-1290 with circ_0026344 or FBP2 was detected using dual-luciferase reporter assay. A xenograft model was established to determine the effect of circ_0026344 on GC tumor growth in vivo. Results. Circ_0026344 expression was dramatically decreased in GC cells and tissues. Circ_0026344 overexpression inhibited GC cell proliferation, migration and invasion. MiR-1290 was predicted as a target of circ_0026344 and miR-1290 overexpression attenuated the anti-tumor effect of circ_0026344 on GC cells. Furthermore, we predicted FBP2 as the target of miR1290. FBP2 knockdown reversed the effects of circ_0026344 knockdown on GC cell malignant behaviors. Functional analysis showed that circ_0026344 upregulated FBP2 expression via miR1290. Additionally, in vivo studies demonstrated that circ_0026344 suppressed GC tumor progression. Conclusion. In conclusion, circ_0026344 inhibited GC cell proliferation via the miR-1290/FBP2 axis, which might provide a new therapeutic target for GC patients.
- PublicationOpen AccessApoptotic effect of selenium mushroom extract from Qinba on multiple myeloma cells(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2023) Yang, Ge; Song, Ze; Wang, Rongli; Sun, YanqinQinba selenium mushroom is a mushroom belonging to the Basidiomycetes family, which is believed to have anti- oxidant, anti-tumoral and antimutagenic activities. However, the efficacy of Qinba selenium mushroom against multiple myeloma has not been confirmed. The present study aimed to investigate the apoptotic effect of FA-2-b-β, the selenium mushroom extract from Qinba on multiple myeloma (MM) cells. The MM RPMI-8226 cells were treated with FA-2-b-β at different concentrations and time points. MM RPMI8226 cell proliferation and apoptosis were detected by the Cell Counting Kit-8 (CCK-8) assay and Annexin V/propidium iodide (PI) assay, RT-QPCR and western blotting analyses were performed to determine the proteins and pathways involved. The results of the present study demonstrated that FA-2-b-β has high antiproliferative activities and strong pro-apoptotic effects on MM RPMI-8226 cells, and its pharmacological effects on proliferation changes occurred in a dose- and time-dependent manner. In addition, we found that FA2-b-β was able to induce cell apoptosis and promote cell cycle arrest at G0/G1 phase. In summary, the results illustrate the involvement of FA-2-b-β in mediating G0/G1 cell cycle arrest and apoptosis in MM RPMI8226 cells, which suggested that FA-2-b-β might have therapeutic potential against multiple myeloma as an effective compound, and may provide useful information for the development of a novel therapeutic target in this area.
- PublicationOpen AccessTreatment of berberine alleviates diabetic nephropathy by reducing iron overload and inhibiting oxidative stress(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2023) Wang, Yujing; Yue, Shuling; Cai, Feng; Zhu, Wen; Zhong, Yuxiang; Chen, Juanjuan; Li, ChunyunDiabetic nephropathy (DN) has become one of the major fatal factors in diabetic patients. The aim of this study was to elucidate the function and mechanism by which berberine exerts renoprotective effects in DN. In this work, we first demonstrated that urinary iron concentration, serum ferritin and hepcidin levels were increased and total antioxidant capacity was significantly decreased in DN rats, while these changes could be partially reversed by berberine treatment. Berberine treatment also alleviated DN-induced changes in the expression of proteins involved in iron transport or iron uptake. In addition, berberine treatment also partially blocked the expression of renal fibrosis markers induced by DN, including MMP2, MMP9, TIMP3, β-arrestin-1, and TGF-β1. In conclusion, the results of this study suggest that berberine may exert renoprotective effects by ameliorating iron overload and oxidative stress and reducing DN
- PublicationOpen AccessThe significance of M1 macrophage should be highlighted in peripheral nerve regeneration(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2023) Feng, Ruiqin; Zhang, PeixunMacrophage influences peripheral nerve regeneration. According to the classical M1/M2 paradigm, the M1 macrophage is an inhibitor of regeneration, while the M2 macrophage is a promoter. However, several studies have shown that M1 macrophages are indispensable for peripheral nerve repair and facilitate many critical processes in axonal regeneration. In this review, we summarized the information on macrophage polarization and focused on the activities of M1 macrophages in regeneration. We also provided some examples where the macrophage phenotypes were regulated to help regeneration. We argued that the coordination of both macrophage phenotypes might be effective in peripheral nerve repair, and a more comprehensive view of macrophages might contribute to macrophage-based immunomodulatory therapies.