Ramipril Alleviates Oxaliplatin-Induced Acute Pain Syndrome in Mice

Oxaliplatin is a key drug for colorectal cancer that causes OXP-induced peripheral neuropathy, a dose-limiting effect characterized by cold and tactile hyperesthesia. The relationship between the sensory nervous system and modulation of the renin-angiotensin system has been described, focusing on pain and neurodegeneration in several animal models. We assessed the effect of the RAS modulator, ramipril, an angiotensin converting-enzyme inhibitor in a mouse model of OXP-induced acute pain syndrome. OXP was administered in Swiss mice at a cumulative dose of 15 mg/kg (3 x 5 mg/kg/3 days, i.p.). RAM was administered i.p. every day from 24 h before the first OXP injection until the end of the experiments. We evaluated OIAS development and treatment effects by sensorimotor tests, intraepidermal nerve fiber and dorsal root ganglia-neuron immunohistochemical analyses, and sciatic nerve ultrastructural analysis. OXP-treated mice showed tactile allodynia and cold hypersensitivity, without motor impairment and evidence of nerve degeneration. RAM prevented cold sensitivity and improved recovery of normal tactile sensitivity in OXP-treated mice. Our finding that RAM alleviates OXP-induced pain is a step towards evaluating its therapeutic potential in patients receiving OXP treatment.

Download Full-text

Mesenchymal Stem Cells Differentiation: Mitochondria Matter in Osteogenesis or Adipogenesis Direction

Current Stem Cell Research & Therapy ◽

10.2174/1574888x15666200324165655 ◽

2020 ◽

Vol 15 (7) ◽

pp. 602-606

Author(s):

Kun Ji ◽

Ling Ding ◽

Xi Chen ◽

Yun Dai ◽

Fangfang Sun ◽

...

Keyword(s):

Tissue Engineering ◽

Stem Cells ◽

Mesenchymal Stem Cells ◽

Therapeutic Potential ◽

Mesodermal Cell ◽

Cell Lineages ◽

Current Review ◽

Differentiation Factors ◽

The Relationship ◽

Msc Differentiation

Mesenchymal Stem Cells (MSCs) exhibit enormous therapeutic potential because of their indispensable regenerative, reparative, angiogenic, anti-apoptotic, and immunosuppressive properties. MSCs can best differentiate into mesodermal cell lineages, including osteoblasts, adipocytes, muscle cells, endothelial cells and chondrocytes. Specific differentiation of MSCs could be induced through limited conditions. In addition to the relevant differentiation factors, drastic changes also occur in the microenvironment to conduct it in an optimal manner for particular differentiation. Recent evidence suggests that the mitochondria participate in the regulating of direction and process of MSCs differentiation. Therefore, our current review focuses on how mitochondria participate in both osteogenesis and adipogenesis of MSC differentiation. Besides that, in our current review, we try to provide a further understanding of the relationship between the behavior of mitochondria and the direction of MSC differentiation, which could optimize current cellular culturing protocols for further facilitating tissue engineering by adjusting specific conditions of stem cells.

Download Full-text

ACE2 Is an Adjacent Element of Atherosclerosis and COVID-19 Pathogenesis

International Journal of Molecular Sciences ◽

10.3390/ijms22094691 ◽

2021 ◽

Vol 22 (9) ◽

pp. 4691

Author(s):

Anastasia V. Poznyak ◽

Evgeny E. Bezsonov ◽

Ali H. Eid ◽

Tatyana V. Popkova ◽

Ludmila V. Nedosugova ◽

...

Keyword(s):

Cardiovascular System ◽

Renin Angiotensin System ◽

Myocardial Damage ◽

Angiotensin Converting Enzyme 2 ◽

Adjacent Element ◽

Chinese Province ◽

Coronavirus Infection ◽

First Time ◽

The Relationship ◽

Interspecies Barrier

COVID-19 is a highly contagious new infection caused by the single-stranded RNA Sars-CoV-2 virus. For the first time, this infection was recorded in December 2019 in the Chinese province of Wuhan. The virus presumably crossed the interspecies barrier and passed to humans from a bat. Initially, the disease was considered exclusively in the context of damage to the respiratory system, but it quickly became clear that the disease also entails serious consequences from various systems, including the cardiovascular system. Among these consequences are myocarditis, myocardial damage, subsequent heart failure, myocardial infarction, and Takotsubo syndrome. On the other hand, clinical data indicate that the presence of chronic diseases in a patient aggravates the course and outcome of coronavirus infection. In this context, the relationship between COVID-19 and atherosclerosis, a condition preceding cardiovascular disease and other disorders of the heart and blood vessels, is particularly interesting. The renin-angiotensin system is essential for the pathogenesis of both coronavirus disease and atherosclerosis. In particular, it has been shown that ACE2, an angiotensin-converting enzyme 2, plays a key role in Sars-CoV-2 infection due to its receptor activity. It is noteworthy that this enzyme is important for the normal functioning of the cardiovascular system. Disruptions in its production and functioning can lead to various disorders, including atherosclerosis.

Download Full-text

Transcranial Direct Current Stimulation as a Treatment Tool for Mild Traumatic Brain Injury

Brain Sciences ◽

10.3390/brainsci11060806 ◽

2021 ◽

Vol 11 (6) ◽

pp. 806

Author(s):

Thorsten Rudroff ◽

Craig D. Workman

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Mild Traumatic Brain Injury ◽

Direct Current ◽

Transcranial Direct Current Stimulation ◽

Therapeutic Potential ◽

Repetitive Transcranial Magnetic Stimulation ◽

Motor Impairment ◽

Direct Current Stimulation ◽

Main Technique

Mild traumatic brain injury (mTBI) has been defined as a transient (<24 h) condition of confusion and/or loss of consciousness for less than 30 min after brain injury and can result in short- and long-term motor and cognitive impairments. Recent studies have documented the therapeutic potential of non-invasive neuromodulation techniques for the enhancement of cognitive and motor function in mTBI. Alongside repetitive transcranial magnetic stimulation (rTMS), the main technique used for this purpose is transcranial direct current stimulation (tDCS). The focus of this review was to provide a detailed, comprehensive (i.e., both cognitive and motor impairment) overview of the literature regarding therapeutic tDCS paradigms after mTBI. A publication search of the PubMed, Scopus, CINAHL, and PsycINFO databases was performed to identify records that applied tDCS in mTBI. The publication search yielded 14,422 records from all of the databases, however, only three met the inclusion criteria and were included in the final review. Based on the review, there is limited evidence of tDCS improving cognitive and motor performance. Surprisingly, there were only three studies that used tDCS in mTBI, which highlights an urgent need for more research to provide additional insights into ideal therapeutic brain targets and optimized stimulation parameters.

Download Full-text

Therapeutic potential of renin angiotensin system inhibitors in cancer cells metastasis

Pathology - Research and Practice ◽

10.1016/j.prp.2020.153010 ◽

2020 ◽

Vol 216 (7) ◽

pp. 153010 ◽

Cited By ~ 2

Author(s):

Milad Hashemzehi ◽

Farimah Beheshti ◽

Seyed Mahdi Hassanian ◽

Gordon A. Ferns ◽

Majid Khazaei ◽

...

Keyword(s):

Cancer Cells ◽

Therapeutic Potential ◽

Renin Angiotensin System ◽

Angiotensin System ◽

Renin Angiotensin

Download Full-text

The renin-angiotensin system and volume overload-induced cardiac hypertrophy in rats. Effects of angiotensin converting enzyme inhibitor versus angiotensin II receptor blocker.

Circulation ◽

10.1161/01.cir.87.3.921 ◽

1993 ◽

Vol 87 (3) ◽

pp. 921-930 ◽

Cited By ~ 63

Author(s):

M Ruzicka ◽

B Yuan ◽

E Harmsen ◽

F H Leenen

Keyword(s):

Angiotensin Ii ◽

Angiotensin Converting Enzyme ◽

Cardiac Hypertrophy ◽

Enzyme Inhibitor ◽

Renin Angiotensin System ◽

Volume Overload ◽

Angiotensin Ii Receptor Blocker ◽

Converting Enzyme ◽

Angiotensin Ii Receptor ◽

Angiotensin System

Download Full-text

Recent Advances in Biomarkers and Regenerative Medicine for Diabetic Neuropathy

International Journal of Molecular Sciences ◽

10.3390/ijms22052301 ◽

2021 ◽

Vol 22 (5) ◽

pp. 2301

Author(s):

Yoshikai Fujita ◽

Tatsufumi Murakami ◽

Akihiro Nakamura

Keyword(s):

Diabetic Neuropathy ◽

Target Gene ◽

Pathological Condition ◽

Nerve Fibers ◽

Nerve Degeneration ◽

Limb Amputation ◽

Sensory Impairment ◽

Mechanical Stimuli ◽

Pathological Conditions ◽

The Relationship

Diabetic neuropathy is one of the most common complications of diabetes. This complication is peripheral neuropathy with predominant sensory impairment, and its symptoms begin with hyperesthesia and pain and gradually become hypoesthesia with the loss of nerve fibers. In some cases, lower limb amputation occurs when hypoalgesia makes it impossible to be aware of trauma or mechanical stimuli. On the other hand, up to 50% of these complications are asymptomatic and tend to delay early detection. Therefore, sensitive and reliable biomarkers for diabetic neuropathy are needed for an early diagnosis of this condition. This review focuses on systemic biomarkers that may be useful at this time. It also describes research on the relationship between target gene polymorphisms and pathological conditions. Finally, we also introduce current information on regenerative therapy, which is expected to be a therapeutic approach when the pathological condition has progressed and nerve degeneration has been completed.

Download Full-text

Brain angiotensin system: a new promise in the management of epilepsy?

Clinical Science ◽

10.1042/cs20201296 ◽

2021 ◽

Vol 135 (6) ◽

pp. 725-730

Author(s):

Alberto Javier Ramos

Keyword(s):

Therapeutic Potential ◽

Renin Angiotensin System ◽

B Cell Lymphoma ◽

Ang Ii ◽

Angiotensin System ◽

Beneficial Effects ◽

System A ◽

Pilocarpine Model ◽

Animal Models Of Epilepsy ◽

Future Work

Abstract Epilepsy is a highly prevalent neurological disease and anti-epileptic drugs (AED) are almost the unique clinical treatment option. A disbalanced brain renin–angiotensin system (RAS) has been proposed in epilepsy and several reports have shown that angiotensin II (Ang II) receptor-1 (ATR1) activation is pro-inflammatory and pro-epileptogenic. In agreement, ATR1 blockage with the repurposed drug losartan has shown benefits in animal models of epilepsy. Processing of Ang II by ACE2 enzyme renders Ang-(1-7), a metabolite that activates the mitochondrial assembly (Mas) receptor (MasR) pathway. MasR activation presents beneficial effects, facilitating vasodilatation, increasing anti-inflammatory and antioxidative responses. In a recent paper published in Clinical Science, Gomes and colleagues (Clin. Sci. (Lond.) (2020) 134, 2263–2277) performed intracerebroventricular (icv) infusion of Ang-(1-7) in animals subjected to the pilocarpine model of epilepsy, starting after the first spontaneous motor seizure (SMS). They showed that this approach reduced the frequency of SMS, restored animal anxiety, increased exploration, and augmented the hippocampal expression of protective catalase enzyme and antiapoptotic protein B-cell lymphoma 2 (Bcl-2). Interestingly, but surprisingly, Gomes and colleagues showed that MasR expression and mTor activity were reduced in the hippocampus of the epileptic Ang-(1-7) treated animals. These results show that Ang-(1-7) administration could represent a new avenue for developing strategies for the management of epilepsy in clinical settings. However, future work is necessary to evaluate the levels of RAS metabolites and the activity of key enzymes in these experimental interventions to completely understand the therapeutic potential of the brain RAS manipulation in epilepsy.

Download Full-text

The Relationship between the Adrenal Tissue Renin-Angiotensin System, Internalization of the Type I Angiotensin II Receptor (AT1) and Angiotensin II Function in the Rat Adrenal Zona Glomerulosa Cell

Advances in Experimental Medicine and Biology - Tissue Renin-Angiotensin Systems ◽

10.1007/978-1-4899-0952-7_22 ◽

1995 ◽

pp. 319-329 ◽

Cited By ~ 6

Author(s):

G. P. Vinson ◽

M. M. Ho ◽

J. R. Puddefoot ◽

R. Teja ◽

S. Barker ◽

...

Keyword(s):

Angiotensin Ii ◽

Renin Angiotensin System ◽

Zona Glomerulosa ◽

Type I ◽

Angiotensin Ii Receptor ◽

Angiotensin System ◽

Renin Angiotensin ◽

Adrenal Tissue ◽

The Relationship

Download Full-text

Thermal responses to central angiotensin II, SQ 20881, and dopamine infusions in sheep

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1985.248.3.r371 ◽

1985 ◽

Vol 248 (3) ◽

pp. R371-R377 ◽

Cited By ~ 2

Author(s):

B. S. Huang ◽

M. J. Kluger ◽

R. L. Malvin

Keyword(s):

Angiotensin Ii ◽

Body Temperature ◽

Enzyme Inhibitor ◽

Renin Angiotensin System ◽

Significant Rise ◽

Ang Ii ◽

Deep Body Temperature ◽

Angiotensin System ◽

Conscious Sheep

The thermoregulatory role of brain angiotensin II (ANG II) was tested by intracerebroventricular (IVT) infusion of ANG II or the converting enzyme inhibitor SQ 20881 (SQ) in 15 conscious sheep. Deep body temperature decreased 0.30 +/- 0.07 degree C (SE) during the 3-h period of IVT ANG II (25 ng/min) infusion (P less than 0.05) and increased 0.50 +/- 0.13 degree C during IVT SQ (1 microgram/min) infusion (P less than 0.01). To determine whether the rise in body temperature after IVT SQ infusion might be the result of a central renin-angiotensin system (RAS), SQ was infused IVT in five conscious sheep 20 h after bilateral nephrectomy. This resulted in a significant rise in body temperature of 0.28 +/- 0.05 degree C (P less than 0.05). When vasopressin antidiuretic hormone (ADH) was infused intravenously at the same time of IVT SQ infusion, the rise in temperature was depressed, but ADH did not lower the temperature below basal. IVT dopamine (20 micrograms/min) increased body temperature by 0.40 +/- 0.04 degree C (P less than 0.01), which was qualitatively similar to the result with IVT SQ. These data support the hypothesis that endogenous brain ANG II may play a role in thermoregulation. Furthermore, plasma ADH level, regulated in part by brain ANG II, is probably not the mediator of that thermoregulation. The similar effects of IVT dopamine and SQ on body temperature strengthen the hypothesis that dopamine may be involved in the central action of brain ANG II.

Download Full-text