scholarly journals Gene and cell therapy of adrenal pathology: achievements and prospects

2021 ◽  
Vol 67 (6) ◽  
pp. 80-89
Author(s):  
O. V. Glazova ◽  
M. V. Vorontsova ◽  
N. Sakr ◽  
L. V. Shevkova ◽  
N. A. Onyanov ◽  
...  
Keyword(s):  
Adrenal Gland ◽  
Cell Therapy ◽  
Cellular Systems ◽  
Hereditary Diseases ◽  
Structural Components ◽  
Animal Cells ◽  
Cellular Mechanisms ◽  
Pathological Conditions ◽  
Gene And Cell Therapy

Our current understanding of the molecular and cellular mechanisms in tissues and organs during normal and pathological conditions opens up substantial prospects for the development of novel approaches to treatment of various diseases. For instance, lifelong replacement therapy is no longer mandatory for the management of some monogenic hereditary diseases. Genome editing techniques that have emerged in the last decade are being actively investigated as tools for correcting mutations in affected organs. Furthermore, new protocols for obtaining various types of human and animal cells and cellular systems are evolving, increasingly reflecting the real structures in vivo. These methods, together with the accompanying gene and cell therapy, are being actively developed and several approaches are already undergoing clinical trials. Adrenal insufficiency caused by a variety of factors can potentially be the target of such therapeutic strategies. The adrenal gland is a highly organized organ, with multiple structural components interacting with each other via a complex network of endocrine and paracrine signals. This review summarizes the findings of studies in the field of structural organization and functioning of the adrenal gland at the molecular level, as well as the modern approaches to the treatment of adrenal pathologies.

In vivo and in vitro evidence for the production of inhibin-like immunoreactivity in human adrenocortical adenomas and normal adrenal glands: relatively high secretion from adenomas manifesting Cushing's syndrome

1995 ◽  
Vol 132 (3) ◽  
pp. 292-299 ◽  
Author(s):  
Yoshihiro Nishi ◽  
Masafumi Haji ◽  
Ryoichi Takayanagi ◽  
Toshihiko Yanase ◽  
Shoichiro Ikuyama ◽  
...  
Keyword(s):  
Adrenal Gland ◽  
Cushing’S Syndrome ◽  
General Circulation ◽  
Adrenal Glands ◽  
Cushing's Syndrome ◽  
Secretion Rate ◽  
Pathological Conditions ◽  
Adrenocortical Adenomas

Nishi Y, Haji M, Takayanagi R, Yanase T, Ikuyama S, Nawata H. In vivo and in vitro evidence for the production of inhibin-like immunoreactivity in human adrenocortical adenomas and normal adrenal glands: relatively high secretion from adenomas manifesting Cushing's syndrome. Eur J Endocrinol 1995;132:292–9. ISSN 0804–4643 To clarify whether adrenal gland secretes inhibin in vivo in physiological or pathological conditions, we measured the levels of inhibin-like immunoreactivity (inhibin-LI) in adrenal veins (A-vein) and compared them with those in inferior vena cava (IVC) using blood samples obtained at catheterization of adrenal vein in the patients with adrenal adenoma manifesting Cushing's syndrome (Cs), aldosterone-producing adenoma, clinically non-functioning adenoma and normal adrenal gland. The tumor sides of A-veins in the patients with adenomas and also both sides of A-veins in subjects with normal adrenal glands showed significantly higher contents of inhibin-LI than their IVC. When the inhibin-LI secretion rate from adrenal gland was estimated by the difference between the levels of A-vein (tumor side) and IVC, Cs adenomas showed the highest secretion rate. Similarly, the tissue inhibin-LI content and the basal secretion rate of inhibit-LI from primary cultured cells were the highest in Cs adenomas. These findings indicated that normal adrenal glands and adrenocortical adenomas produced and secreted inhibin-LI into the general circulation in vivo and Cs adenomas have relatively high capacity for secreting inhibin-LI, and the present study provided the first in vivo evidence for adrenal inhibin-LI production in pathological conditions Yoshihiro Nishi, Third Department of Internal Medicine, Faculty of Medicine, Kyushu University, Maidashi 3-1-1, Higashi-Ku, Fukuoka 812, Japan

Autologous transplantation of mesenchymal stem cells into the portal vein of the miniature pig; a preliminary experiment for NOTES approach

2019 ◽  
Vol 98 (9) ◽  
pp. 350-355
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Cell Therapy ◽  
Portal Vein ◽  
Liver Parenchyma ◽  
Miniature Pig ◽  
Hepatic Diseases ◽  
Study Results

Introduction: There is evidence that mesenchymal stem cells (MSCs) could trans-differentiate into the liver cells in vitro and in vivo and thus may be used as an unfailing source for stem cell therapy of liver disease. Combination of MSCs (with or without their differentiation in vitro) and minimally invasive procedures as laparoscopy or Natural Orifice Transluminal Endoscopic Surgery (NOTES) represents a chance for many patients waiting for liver transplantation in vain. Methods: Over 30 millions of autologous MSCs at passage 3 were transplanted via the portal vein in an eight months old miniature pig. The deposition of transplanted cells in liver parenchyma was evaluated histologically and the trans-differential potential of CM-DiI labeled cells was assessed by expression of pig albumin using immunofluorescence. Results: Three weeks after transplantation we detected the labeled cells (solitary, small clusters) in all 10 samples (2 samples from each lobe) but no diffuse distribution in the samples. The localization of CM-DiI+ cells was predominantly observed around the portal triads. We also detected the localization of albumin signal in CM-DiI labeled cells. Conclusion: The study results showed that the autologous MSCs (without additional hepatic differentiation in vitro) transplantation through the portal vein led to successful infiltration of intact miniature pig liver parenchyma with detectable in vivo trans-differentiation. NOTES as well as other newly developed surgical approaches in combination with cell therapy seem to be very promising for the treatment of hepatic diseases in near future.

Modern approaches to peripheral nerve regeneration after injury: the prospects of gene and cell therapy

2017 ◽  
Author(s):  
M. Karagyaur ◽  
P. Makarevich ◽  
E. Shevchenko ◽  
D. Stambolsky ◽  
N. Kalinina ◽  
...  
Keyword(s):  
Cell Therapy ◽  
Peripheral Nerve ◽  
Nerve Regeneration ◽  
Peripheral Nerve Regeneration ◽  
Gene And Cell Therapy

Anthocyanins As Modulators of Cell Redox-Dependent Pathways in Non-Communicable Diseases

2020 ◽  
Vol 27 (12) ◽  
pp. 1955-1996 ◽  
Author(s):  
Antonio Speciale ◽  
Antonella Saija ◽  
Romina Bashllari ◽  
Maria Sofia Molonia ◽  
Claudia Muscarà ◽  
...  
Keyword(s):  
Human Health ◽  
Biological Activities ◽  
Wide Spectrum ◽  
Antioxidant Defenses ◽  
Noncommunicable Diseases ◽  
Protective Effects ◽  
Pathological Conditions ◽  
Chronic Pulmonary Diseases ◽  
Underlying Mechanisms

: Chronic Noncommunicable Diseases (NCDs), mostly represented by cardiovascular diseases, diabetes, chronic pulmonary diseases, cancers, and several chronic pathologies, are one of the main causes of morbidity and mortality, and are mainly related to the occurrence of metabolic risk factors. Anthocyanins (ACNs) possess a wide spectrum of biological activities, such as anti-inflammatory, antioxidant, cardioprotective and chemopreventive properties, which are able to promote human health. Although ACNs present an apparent low bioavailability, their metabolites may play an important role in the in vivo protective effects observed. : This article directly addresses the scientific evidences supporting that ACNs could be useful to protect human population against several NCDs not only acting as antioxidant but through their capability to modulate cell redox-dependent signaling. In particular, ACNs interact with the NF-κB and AP-1 signal transduction pathways, which respond to oxidative signals and mediate a proinflammatory effect, and the Nrf2/ARE pathway and its regulated cytoprotective proteins (GST, NQO, HO-1, etc.), involved in both cellular antioxidant defenses and elimination/inactivation of toxic compounds, so countering the alterations caused by conditions of chemical/oxidative stress. In addition, supposed crosstalks could contribute to explain the protective effects of ACNs in different pathological conditions characterized by an altered balance among these pathways. Thus, this review underlines the importance of specific nutritional molecules for human health and focuses on the molecular targets and the underlying mechanisms of ACNs against various diseases.

Chinese Medicine Protein and Peptide in Gene and Cell Therapy

2019 ◽  
Vol 20 (3) ◽  
pp. 251-264 ◽  
Author(s):  
Yinlu Feng ◽  
Zifei Yin ◽  
Daniel Zhang ◽  
Arun Srivastava ◽  
Chen Ling
Keyword(s):  
Chinese Medicine ◽  
Cell Therapy ◽  
Future Research ◽  
The Past ◽  
Promising Strategy ◽  
Wide Range ◽  
New Directions ◽  
Gene And Cell Therapy ◽  
Proteins And Peptides

The success of gene and cell therapy in clinic during the past two decades as well as our expanding ability to manipulate these biomaterials are leading to new therapeutic options for a wide range of inherited and acquired diseases. Combining conventional therapies with this emerging field is a promising strategy to treat those previously-thought untreatable diseases. Traditional Chinese medicine (TCM) has evolved for thousands of years in China and still plays an important role in human health. As part of the active ingredients of TCM, proteins and peptides have attracted long-term enthusiasm of researchers. More recently, they have been utilized in gene and cell therapy, resulting in promising novel strategies to treat both cancer and non-cancer diseases. This manuscript presents a critical review on this field, accompanied with perspectives on the challenges and new directions for future research in this emerging frontier.

scholarly journals Molecular and Cellular Mechanisms of Metformin in Cervical Cancer

Cancers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2545
Author(s):  
Ya-Hui Chen ◽  
Po-Hui Wang ◽  
Pei-Ni Chen ◽  
Shun-Fa Yang ◽  
Yi-Hsuan Hsiao
Keyword(s):  
Cervical Cancer ◽  
Potential Role ◽  
Treatment Options ◽  
Cellular Mechanisms ◽  
Anticancer Effects ◽  
Clinical Benefits ◽  
Underlying Mechanisms

Cervical cancer is one of the major gynecologic malignancies worldwide. Treatment options include chemotherapy, surgical resection, radiotherapy, or a combination of these treatments; however, relapse and recurrence may occur, and the outcome may not be favorable. Metformin is an established, safe, well-tolerated drug used in the treatment of type 2 diabetes; it can be safely combined with other antidiabetic agents. Diabetes, possibly associated with an increased site-specific cancer risk, may relate to the progression or initiation of specific types of cancer. The potential effects of metformin in terms of cancer prevention and therapy have been widely studied, and a number of studies have indicated its potential role in cancer treatment. The most frequently proposed mechanism underlying the diabetes–cancer association is insulin resistance, which leads to secondary hyperinsulinemia; furthermore, insulin may exert mitogenic effects through the insulin-like growth factor 1 (IGF-1) receptor, and hyperglycemia may worsen carcinogenesis through the induction of oxidative stress. Evidence has suggested clinical benefits of metformin in the treatment of gynecologic cancers. Combining current anticancer drugs with metformin may increase their efficacy and diminish adverse drug reactions. Accumulating evidence is indicating that metformin exerts anticancer effects alone or in combination with other agents in cervical cancer in vitro and in vivo. Metformin might thus serve as an adjunct therapeutic agent for cervical cancer. Here, we reviewed the potential anticancer effects of metformin against cervical cancer and discussed possible underlying mechanisms.

A Sensitive Method for Assay of Mixed-Function Oxygenase (p-450 complex) in Cell Culture

1988 ◽  
Vol 15 (3) ◽  
pp. 219-223
Author(s):  
Jørgen Clausen ◽  
Søren Achim Nielsen
Keyword(s):  
Human Lymphocytes ◽  
Cellular Systems ◽  
Metabolic Effects ◽  
Assay Method ◽  
Related Family ◽  
Oxygenase Activity ◽  
Metabolic Transformation ◽  
Mixed Function Oxygenase

The mixed-function oxygenase system involved in the metabolism of drugs and xenobiotics has been extensively studied in various animal species and in various organs (1). It is now apparent that in humans the p-450 complex is one representative of a related family, expressed by 13 c-DNA genes showing approximately 36% similarity between the different subfamilies (2). In order to compare the in vivo and in vitro metabolic effects of drugs and xenobiotics, the induction capabilities of the mixed-function oxygenase must be known. The most sensitive non-isotopic assay system for determination of mixed-function oxygenase activity is the method of Nebert & Gelboin (3,4), which is based on the metabolic transformation of benzo-(a)-pyrene to its fluorescent hydroxyl derivatives (5). However, the levels of the mixed-function oxygenase enzymes in different cellular systems show great variations, with the highest activities in liver cells. Therefore, in order to use human lymphocytes and other cellular systems with low mixed-function oxygenase activities, the assay method for determining oxygenase activity must have the highest possible sensitivity. The present communication is devoted to a study aimed at increasing the sensitivity of Nebert & Gelboin's methods for assay of mixed-function oxygenase subfamilies using benzo-(a)-pyrene as a substrate.

scholarly journals Hippocampal Interneurons are Required for Trace Eyeblink Conditioning in Mice

2021 ◽  
Author(s):  
Wei-Wei Zhang ◽  
Rong-Rong Li ◽  
Jie Zhang ◽  
Jie Yan ◽  
Qian-Hui Zhang ◽  
...  
Keyword(s):  
Eyeblink Conditioning ◽  
Pyramidal Cells ◽  
Conditioned Eyeblink ◽  
Cellular Mechanisms ◽  
Sustained Activity ◽  
Early Acquisition ◽  
Freely Moving ◽  
Trace Eyeblink Conditioning

AbstractWhile the hippocampus has been implicated in supporting the association among time-separated events, the underlying cellular mechanisms have not been fully clarified. Here, we combined in vivo multi-channel recording and optogenetics to investigate the activity of hippocampal interneurons in freely-moving mice performing a trace eyeblink conditioning (tEBC) task. We found that the hippocampal interneurons exhibited conditioned stimulus (CS)-evoked sustained activity, which predicted the performance of conditioned eyeblink responses (CRs) in the early acquisition of the tEBC. Consistent with this, greater proportions of hippocampal pyramidal cells showed CS-evoked decreased activity in the early acquisition of the tEBC. Moreover, optogenetic suppression of the sustained activity in hippocampal interneurons severely impaired acquisition of the tEBC. In contrast, suppression of the sustained activity of hippocampal interneurons had no effect on the performance of well-learned CRs. Our findings highlight the role of hippocampal interneurons in the tEBC, and point to a potential cellular mechanism subserving associative learning.

scholarly journals Comparative analysis of mouse bone marrow and adipose tissue mesenchymal stem cells for critical limb ischemia cell therapy

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Pegah Nammian ◽  
Seyedeh-Leili Asadi-Yousefabad ◽  
Sajad Daneshi ◽  
Mohammad Hasan Sheikhha ◽  
Seyed Mohammad Bagher Tabei ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Adipose Tissue ◽  
Cell Therapy ◽  
Femoral Artery ◽  
Critical Limb Ischemia ◽  
Limb Ischemia

Abstract Introduction Critical limb ischemia (CLI) is the most advanced form of peripheral arterial disease (PAD) characterized by ischemic rest pain and non-healing ulcers. Currently, the standard therapy for CLI is the surgical reconstruction and endovascular therapy or limb amputation for patients with no treatment options. Neovasculogenesis induced by mesenchymal stem cells (MSCs) therapy is a promising approach to improve CLI. Owing to their angiogenic and immunomodulatory potential, MSCs are perfect candidates for the treatment of CLI. The purpose of this study was to determine and compare the in vitro and in vivo effects of allogeneic bone marrow mesenchymal stem cells (BM-MSCs) and adipose tissue mesenchymal stem cells (AT-MSCs) on CLI treatment. Methods For the first step, BM-MSCs and AT-MSCs were isolated and characterized for the characteristic MSC phenotypes. Then, femoral artery ligation and total excision of the femoral artery were performed on C57BL/6 mice to create a CLI model. The cells were evaluated for their in vitro and in vivo biological characteristics for CLI cell therapy. In order to determine these characteristics, the following tests were performed: morphology, flow cytometry, differentiation to osteocyte and adipocyte, wound healing assay, and behavioral tests including Tarlov, Ischemia, Modified ischemia, Function and the grade of limb necrosis scores, donor cell survival assay, and histological analysis. Results Our cellular and functional tests indicated that during 28 days after cell transplantation, BM-MSCs had a great effect on endothelial cell migration, muscle restructure, functional improvements, and neovascularization in ischemic tissues compared with AT-MSCs and control groups. Conclusions Allogeneic BM-MSC transplantation resulted in a more effective recovery from critical limb ischemia compared to AT-MSCs transplantation. In fact, BM-MSC transplantation could be considered as a promising therapy for diseases with insufficient angiogenesis including hindlimb ischemia.

scholarly journals Probing the Intracellular Bio-Nano Interface in Different Cell Lines with Gold Nanostars

Nanomaterials ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 1183
Author(s):  
Cecilia Spedalieri ◽  
Gergo Péter Szekeres ◽  
Stephan Werner ◽  
Peter Guttmann ◽  
Janina Kneipp
Keyword(s):  
Cell Line ◽  
Cell Lines ◽  
Early Stage ◽  
Protein Corona ◽  
Fibroblast Cell ◽  
Ultrastructural Level ◽  
Epithelial Cell Line ◽  
Animal Cells ◽  
Gold Nanostars

Gold nanostars are a versatile plasmonic nanomaterial with many applications in bioanalysis. Their interactions with animal cells of three different cell lines are studied here at the molecular and ultrastructural level at an early stage of endolysosomal processing. Using the gold nanostars themselves as substrate for surface-enhanced Raman scattering, their protein corona and the molecules in the endolysosomal environment were characterized. Localization, morphology, and size of the nanostar aggregates in the endolysosomal compartment of the cells were probed by cryo soft-X-ray nanotomography. The processing of the nanostars by macrophages of cell line J774 differed greatly from that in the fibroblast cell line 3T3 and in the epithelial cell line HCT-116, and the structure and composition of the biomolecular corona was found to resemble that of spherical gold nanoparticles in the same cells. Data obtained with gold nanostars of varied morphology indicate that the biomolecular interactions at the surface in vivo are influenced by the spike length, with increased interaction with hydrophobic groups of proteins and lipids for longer spike lengths, and independent of the cell line. The results will support optimized nanostar synthesis and delivery for sensing, imaging, and theranostics.

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