156 Epigenomics and transcriptomics of muscle and liver tissues from in vitro- and in vivo-produced dairy calves at 3 months of age

2022 ◽  
Vol 34 (2) ◽  
pp. 316
Author(s):  
M. Rabaglino ◽  
J. Bojsen-Møller Secher ◽  
P. Hyttel ◽  
H. Kadarmideen
Keyword(s):  
Dairy Calves ◽  
Liver Tissues

Genetic engineered MSCs are attractive possibilities for regenerative stem-cell therapy to treat several liver diseases

2021 ◽  
Author(s):  
Moataz Dowaidar
Keyword(s):  
Stem Cell ◽  
Genetic Engineering ◽  
Genetically Modified ◽  
Tumor Development ◽  
Trophic Factors ◽  
Surface Marker Expression ◽  
Functional Features ◽  
Liver Tissues

While MSCs are intriguing candidates for stem cell-based regenerative therapy to treat numerous liver ailments, further study is needed to improve their therapeutic advantages. By delivering particular genes or trophic factors to wounded liver tissues, genetic engineering boosts MSC's therapeutic efficacy. Moreover, overexpression of foreign genes in damaged liver tissues will improve the hepatogenic differentiation, homing, anti-inflammatory, immunosuppressive, anti-apoptotic, antifibrotic, and cancer capacities of MSCs. MSCs are transformed into HLCs with mature hepatocyte capabilities when transcription factors are supplied; however, HLCs derived from genetically modified MSCs are not used to treat liver disease.This is because, after extended growing in vitro, both primary hepatocytes and HLCs lose their liver-specific functions. Difficulty in using genetic engineering in MSCs. For starters, there is no recognized genetic modification approach to homogenize the functional features of MSCs, resulting in substantial variation in surface marker expression, proliferation, and differentiation in gene-modified MSCs. Second, MSC genetic alteration creates safety issues and unpredictability, such as tumor development or in vivo differentiation. In the future, new techniques with effective gene carriers, appropriate transfection conditions, good targeted specificity and lesser cytotoxicity should be developed. As MSCs respond variably to local microenvironments, people with distinct liver illnesses may have variable responses to genetically altered MSC transplantation. Finally, we underline that all scientific challenges must be resolved before genetically modified MSC therapy may be employed in clinical practice for liver problem patients.

scholarly journals Evaluation of Sirt1 And Foxo’s In Primary Tumor And Distant Organ Metastasis Invaded By Benign And Highly Metastatic Breast Carcinoma Cells Under In Vitro And In Vivo Conditions.

2021 ◽  
Author(s):  
Sayra Dilmac ◽  
Nilay Kuscu ◽  
Ayse Caner ◽  
Sendegul Yildirim ◽  
Burcak Yoldas ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Primary Tumor ◽  
Metastatic Breast ◽  
Signal Pathways ◽  
Breast Cancers ◽  
Primary Tumors ◽  
Metastatic Breast Carcinoma ◽  
Liver Tissues

Abstract Breast cancer is the second most common cancer in women. In malignant breast cancers, tumor cells have the potential to metastasize to distant organs through the lymphatic system and blood circulation. The aim of this study is to evaluate the expression of SIRT1 and FoxO proteins in metastatic and nonmetastatic breast cancer cells and distant organs metastasis. In our study, SIRT1, p53, p21, and FoxO proteins have been evaluated in metastatic 4TLM and non-metastatic 67NR cell lines by immunocytochemistry in vitro and also in mice breast cancer model in vivo. Cells were orthotopically injected to mammary fat pads of 8-10 weeks old Balb/c female mice. Primary tumor, lung and liver tissues were removed and expressions of these proteins were evaluated by immunohistochemistry, western blot and RT-PCR. In addition, signal pathways that are related to SIRT and FoxO proteins were examined by using IPA core analysis. TCGA database was browsed for investigation of different genes.In primary tumors, SIRT1, p21, p53, E2F1 and FoxO expressions were higher in 67NR compared to 4TLM. In metastatic lung and liver tissues, the expression levels of SIRT1, FoxO1, FoxO3a and FoxO4 proteins were increased in 4TLM compared to 67NR. IPA and TCGA analysis have also revealed that SIRT1 and FoxO proteins are lower in primary tumors, but increased in metastatic stages. In conclusion, in primary tumors SIRT1 and FoxO expressions were decreased in 4TLM compared to 67NR. Moreover, SIRT1 and FoxO, especially expressed in metastatic cells. High level of FoxO expressions in metastatic stages in TNBC patients also supports its association with metastasis. Our findings suggest that SIRT1 and FoxO’s have crucial role in tumor progression metastatic process in breast cancer.

scholarly journals Bicelin (B-cell lymphoma 2 inhibitor) a Highly Safe DNA-based Anti-cancer Drug Showed No in vivo Cytopenia, Nephrotoxicity and/or Hepatotoxicity

2020 ◽  
Author(s):  
Reza Sheikhnejad ◽  
Farzaneh Ashrafi ◽  
Ardeshir Talebi ◽  
Bahar Mazaheri ◽  
Fatemeh Moslemi ◽  
...  
Keyword(s):  
Side Effects ◽  
Hodgkin’S Lymphoma ◽  
B Cell Lymphoma ◽  
Hodgkin's Lymphoma ◽  
Cancer Drug ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma ◽  
Liver Tissues

Abstract Background: Non-Hodgkin's lymphoma is the seventh most common cancer in clinic. Lymphoma could be treated with newly developed anti-apoptotic small molecule inhibitors of bcl-2 such as ABT-199 or venetoclax. However most small molecules present numerous side effects and cancer becomes resistance to them rapidly. PNT100 is a DNA-based bcl-2 inhibitor that has shown great efficacy and safety in treating non-Hodgkin's lymphoma tumors. However, liposomal carrier(smarticles) that was used to deliver PNT100 eventually failed to produce robust efficacy in the latest clinical trial conducted by ProNai Therapeutics (now called Sierra Technology). The high cost of liposomal carriers, makes this targeted drug less affordable. In addition, the liposomal components may also present some minor side effects as reported in pilot phase II trial [17-22]. In this study, we eliminated liposome and used a specific Epigenic modification to deliver this 24bp oligonucleotides (PNT100) without using additional chemicals and named it Bicelin. Methods: In this study, the safety of Bicelin was determined by evaluating the cytopenia, nephrotoxicity and hepatotoxicity effects of this drug in healthy animal model (Rats). The rats in experimental group were received Bicelin (20 mg/kg/day) for 5 days a week. The treatment was continued for 3 consecutive weeks. The blood and urine samples were collected for evaluation and the rats were then sacrificed. The kidneys and liver tissues were fixed in formalin 10% to perform histological investigation using H&E staining. Results: The in vitro and in vivo results clearly demonstrate that Bicelin is target specific and highly safe. We observed no cytopenia when blood tests were performed after 15 consecutive injection of Bicelin; Urine analysis revealed no significant differences between experimental and control group and there was no nephrotoxicity or hepatotoxicity when kidney and liver tissues were examined. Conclusion: based on our in vitro and in vivo safety studies, our bcl2 inhibitor, Bicelin is much safer and about 10-fold more effective than its liposomal form (PNT2258). Considering preclinical, phase I and II studies of PNT2258, Bicelin is expected to be very safe and effective in clinic.

scholarly journals Cytosolic sulfotransferase 2B1b promotes hepatocyte proliferation gene expression in vivo and in vitro

2012 ◽  
Vol 303 (3) ◽  
pp. G344-G355 ◽  
Author(s):  
Xin Zhang ◽  
Qianming Bai ◽  
Leyuan Xu ◽  
Genta Kakiyama ◽  
William M. Pandak ◽  
...  
Keyword(s):  
Gene Expression ◽  
Mouse Liver ◽  
Rat Hepatocytes ◽  
Hepatocyte Proliferation ◽  
Gene Expressions ◽  
Primary Rat Hepatocytes ◽  
Liver Proliferation ◽  
Liver Tissues

Cytosolic sulfotransferase 2B1b (SULT2B1b) catalyzes the sulfation of 3β-hydroxysteroids and functions as a selective cholesterol and oxysterol sulfotransferase. Activation of liver X receptors (LXRs) by oxysterols has been known to be an antiproliferative factor. Overexpression of SULT2B1b impairs LXR's response to oxysterols, by which it regulates lipid metabolism. The aim of this study was to investigate in vivo and in vitro effects of SULT2B1b on liver proliferation and the underlying mechanisms. Primary rat hepatocytes and C57BL/6 mice were infected with adenovirus encoding SULT2B1b. Liver proliferation was determined by measuring the proliferating cell nuclear antigen (PCNA) immunostaining labeling index. The correlation between SULT2B1b and PCNA expression in mouse liver tissues was determined by double immunofluorescence. Gene expressions were evaluated by quantitative real-time PCR and Western blot analysis. SULT2B1b overexpression in mouse liver tissues increased PCNA-positive cells in a dose- and time-dependent manner. The increased expression of PCNA in mouse liver tissues was only observed in the SULT2B1b transgenic cells. Small interference RNA SULT2B1b significantly inhibited cell cycle regulatory gene expressions in primary rat hepatocytes. LXR activation by T0901317 effectively suppressed SULT2B1b-induced gene expression in vivo and in vitro. SULT2B1b may promote hepatocyte proliferation by inactivating oxysterol/LXR signaling.

scholarly journals In Vivo (Dairy Calves) and in Vitro Studies with Surface-Active Agents

1954 ◽  
Vol 37 (6) ◽  
pp. 737-743 ◽  
Author(s):  
H.H. Voelker ◽  
R.S. Allen ◽  
N.L. Jacobson ◽  
J.T. Blake
Keyword(s):  
In Vitro Studies ◽  
Dairy Calves ◽  
Surface Active Agents ◽  
Surface Active

scholarly journals Cellular retinol binding protein-1 inhibits cancer stemness via upregulating WIF1 to suppress Wnt/β-catenin pathway in hepatocellular carcinoma

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Xiangye Liu ◽  
Wenhua Shan ◽  
Tingting Li ◽  
Xiaoge Gao ◽  
Fanyun Kong ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Retinoic Acid ◽  
Cell Growth ◽  
Signaling Pathway ◽  
Normal Liver ◽  
Retinol Binding Protein ◽  
Cancer Stemness ◽  
Liver Tissues

Abstract Background CRBP-1, a cytosolic chaperone of vitamin A, is identified in a serious number of cancers; however, its biological role in hepatocellular carcinoma (HCC) needs to be further explored. The aim of our present study is to explore the roles and mechanisms of CRBP-1 in regulating liver cancer by using in vitro and in vivo biology approaches. Methods The expression level of CRBP-1 was detected using immunohistochemistry in HCC and matching adjacent non-tumorous liver tissues. Following established stable CRBP-1 overexpressed HCC cell lines, the cell growth and tumorigenicity were investigated both in vitro and in vivo. Intracellular retinoic acid was quantified by ELISA. The relationship between CRBP-1 and WIF1 was validated by using dual luciferase and ChIP analyses. Results The low expression of CRBP-1 was observed in HCC tissues compared to the normal liver tissues, while high CRBP-1 expression correlated with clinicopathological characteristics and increased overall survival in HCC patients. Overexpression of CRBP-1 significantly inhibited cell growth and tumorigenicity both in vitro and in vivo. Moreover, overexpression of CRBP-1 suppressed tumorsphere formation and cancer stemness related genes expression in HCC. Mechanically, CRBP-1 inhibited Wnt/β-catenin signaling pathway to suppress cancer cell stemness of HCC. Furthermore, our results revealed that CRBP-1 could increase the intracellular levels of retinoic acid, which induced the activation of RARs/RXRs leading to the transcriptional expression of WIF1, a secreted antagonist of the Wnt/β-catenin signaling pathway, by physically interacting with the region on WIF1 promoter. Conclusion Our findings reveal that CRBP-1 is a crucial player in the initiation and progression of HCC, which provide a novel independent prognostic biomarker and therapeutic target for the diagnosis and treatment of HCC.

scholarly journals Bicelin (B-cell lymphoma 2 inhibitor) a Highly Safe DNA-based Anti-cancer Drug Showed No in vivo Cytopenia, Nephrotoxicity and/or Hepatotoxicity

2021 ◽  
Author(s):  
Reza Sheikhnejad ◽  
Farzaneh Ashrafi ◽  
Ardeshir Talebi ◽  
Bahar Mazaheri ◽  
Fatemeh Moslemi ◽  
...  
Keyword(s):  
Side Effects ◽  
Hodgkin’S Lymphoma ◽  
B Cell Lymphoma ◽  
Hodgkin's Lymphoma ◽  
Cancer Drug ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma ◽  
Liver Tissues

Abstract Background: Non-Hodgkin's lymphoma is the seventh most common cancer in clinic. Lymphoma could be treated with newly developed anti-apoptotic small molecule inhibitors of bcl-2 such as ABT-199 or venetoclax. However most small molecules present numerous side effects and cancer becomes resistance to them rapidly. PNT100 is a DNA-based bcl-2 inhibitor that has shown great efficacy and safety in treating non-Hodgkin's lymphoma tumors. However, liposomal carrier(smarticles) that was used to deliver PNT100 eventually failed to produce robust efficacy in the latest clinical trial conducted by ProNai Therapeutics (now called Sierra Technology). The high cost of liposomal carriers, makes this targeted drug less affordable. In addition, the liposomal components may also present some minor side effects as reported in pilot phase II trial [17-22]. In this study, we eliminated liposome and used a specific Epigenic modification to deliver this 24bp oligonucleotides (PNT100) without using additional chemicals and named it Bicelin.Methods: In this study, the safety of Bicelin was determined by evaluating the cytopenia, nephrotoxicity and hepatotoxicity effects of this drug in healthy animal model (Rats). The rats in experimental group were received Bicelin (20 mg/kg/day) for 5 days a week. The treatment was continued for 3 consecutive weeks. The blood and urine samples were collected for evaluation and the rats were then sacrificed. The kidneys and liver tissues were fixed in formalin 10% to perform histological investigation using H&E staining.Results: The in vitro and in vivo results clearly demonstrate that Bicelin is target specific and highly safe. We observed no cytopenia when blood tests were performed after 15 consecutive injection of Bicelin; Urine analysis revealed no significant differences between experimental and control group and there was no nephrotoxicity or hepatotoxicity when kidney and liver tissues were examined.Conclusion: based on our in vitro and in vivo safety studies, our bcl2 inhibitor, Bicelin is much safer and about 10-fold more effective than its liposomal form (PNT2258). Considering preclinical, phase I and II studies of PNT2258, Bicelin is expected to be very safe and effective in clinic.

Induction and Differentiation of Dental Epithelium in Vivo and in Vitro

1982 ◽  
Vol 40 ◽  
pp. 142-145
Author(s):  
E. J. Kollar
Keyword(s):  
Connective Tissue ◽  
Oral Mucosa ◽  
Basal Lamina ◽  
Functional Derivatives ◽  
Specific Source ◽  
Dental Epithelium ◽  
Connective Tissue Stroma

The differentiation and maintenance of many specialized epithelial structures are dependent on the underlying connective tissue stroma and on an intact basal lamina. These requirements are especially stringent in the development and maintenance of the skin and oral mucosa. The keratinization patterns of thin or thick cornified layers as well as the appearance of specialized functional derivatives such as hair and teeth can be correlated with the specific source of stroma which supports these differentiated expressions.

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