Exercise Training-induced Modulation in Microenvironment of Rat Mammary Neoplasms

AbstractDespite the importance attributed to exercise training in the breast cancer (BC) continuum, the underlying mechanisms modulating tumor behavior are unknown. We evaluated the effects of long-term moderate-exercise in the development of mammary tumors, and studied the microenvironment of infiltrative lesions, the amount of connective tissue, and balance between cellular proliferation/death.Fifty Sprague-Dawley rats, randomly assigned into four groups: two control groups (sedentary and exercised) and two models of BC groups (sedentary and exercised) induced by N-methyl-N-nitrosoureia (MNU), were sacrificed after 35 weeks of moderate-exercise, and all perceptible tumors were removed for histological and immunohistochemistry analysis.The median number of infiltrative-lesions per animal was lower in the MNU exercised animals (p=0.02). More than one histological pattern was identified, and papillary carcinoma was the most frequent in both groups. Within infiltrative-lesions, the number of immunopositive cells per μm2 of Ki67 was lower in exercised animals (p=0.002). This presents increased cell death per μm2 (p=0.019). Tumors from sedentary animals had a higher expression of collagen deposition (p=0.027).Long-term moderate-exercise has beneficial effects in tumor development with a diminished prevalence of malignancy. Within infiltrative-lesions, moderate-exercise improves the balance between cell-proliferation and cell-death with decreased connective tissue that suggests lower tumor aggressiveness.

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Cost-effectiveness analysis of long-term moderate exercise training in chronic heart failure

The American Journal of Cardiology ◽

10.1016/s0002-9149(01)01434-5 ◽

2001 ◽

Vol 87 (8) ◽

pp. 984-988 ◽

Cited By ~ 65

Author(s):

Demetrios Georgiou ◽

Yu Chen ◽

Sheila Appadoo ◽

Romualdo Belardinelli ◽

Richard Greene ◽

...

Keyword(s):

Heart Failure ◽

Cost Effectiveness ◽

Chronic Heart Failure ◽

Exercise Training ◽

Cost Effectiveness Analysis ◽

Moderate Exercise ◽

Effectiveness Analysis ◽

Moderate Exercise Training

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Benefits of exercise training on cardiovascular dysfunction: molecular and integrative

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00516.2018 ◽

2018 ◽

Vol 315 (4) ◽

pp. H1027-H1031 ◽

Cited By ~ 4

Author(s):

Irving H. Zucker ◽

Timothy I. Musch

Keyword(s):

Exercise Training ◽

Cardiovascular Disorders ◽

Chronic Exercise ◽

Peripheral Vasculature ◽

Novel Studies ◽

Beneficial Effects ◽

Circulatory Physiology ◽

Genetic Mechanisms ◽

Intense Research

Exercise training has been shown to ameliorate a wide variety of cardiovascular disorders. The mechanisms by which long-term benefits of exercise training are mediated remains incomplete, despite intense research in this area. Exactly how the act of chronic exercise improves function in every tissue is unknown, but many of the cellular, molecular, and genetic mechanisms are becoming progressively clearer. This “Perspectives” article reviews the contributions of 15 articles published in the American Journal of Physiology-Heart and Circulatory Physiology in response to a Call for Papers in this area. Here, we summarize the contributions of these studies at the cardiac, vascular, immune, and molecular levels. We discuss the translational benefit of these studies and conclude that the beneficial effects of exercise training in cardiovascular disease is due to a large interplay of cellular and molecular mediators in the heart and peripheral vasculature as well as changes in neural elements that regulate blood pressure and blood flow. Readers are encouraged to evaluate and learn from this collection of novel studies.

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Losartan increases NO release in afferent arterioles during regression of l-NAME-induced renal damage

AJP Renal Physiology ◽

10.1152/ajprenal.00056.2009 ◽

2010 ◽

Vol 298 (5) ◽

pp. F1170-F1177 ◽

Cited By ~ 5

Author(s):

Frank Helle ◽

Bjarne M. Iversen ◽

Christos Chatziantoniou

Keyword(s):

Blood Pressure ◽

Recovery Period ◽

Ang Ii ◽

Sprague Dawley ◽

Beneficial Effects ◽

No Release ◽

Afferent Arterioles ◽

And Function ◽

Dose Responses

Inhibition of nitric oxide synthesis (NOS) induces hypertension and heavy proteinuria. Renal structure and function have shown striking improvement after interventions targeting ANG II or endothelin (ET) receptors in rats recovering after long-term NOS inhibition. To search for mechanisms underlying losartan-assisted regression of renal disease in rodents, we measured NO release and contractility to ET in afferent arterioles (AAs) from Sprague-Dawley rats recovering for 2 wk after 4 wk of NG-nitro-l-arginine methyl ester treatment. Losartan administration during the recovery period decreased blood pressure (113 ± 4 vs. 146 ± 5 mmHg, P < 0.01), reduced protein/creatinine ratio more (proteinuria decrease: Δ1,836 ± 214 vs. Δ1,024 ± 180 mg/mmol, P < 0.01), and normalized microvascular hypertrophy (AA media/lumen ratio: 1.74 ± 0.05 vs. 2.09 ± 0.08, P < 0.05) compared with no treatment. In diaminofluorescein-FM-loaded AAs from losartan-treated animals, NO release (% of baseline) was increased compared with untreated animals after stimulation with 10−7 M ACh (118 ± 4 vs. 90 ± 7%, t = 560 s, P < 0.001) and 10−9 M ET (123 ± 4 vs. 101 ± 5%, t = 560 s, P < 0.001). There was also a blunted contractile response to 10−7 M ET in AAs from losartan-treated animals compared with untreated animals (Δ4.01 ± 2.9 vs. Δ14.6 ± 1.7 μm, P < 0.01), which disappeared after acute NOS inhibition (Δ10.7 ± 3.7 vs. Δ12.5 ± 2.9 μm, not significant). Contractile dose responses to ET (10−9, 10−8, 10−7 M) were enhanced by NOS inhibition and blunted by exogenous NO (10−2 mM S-nitroso- N-acetyl-penicillamine) in losartan-treated but not in untreated vessels. Reducing blood pressure similar to losartan with hydralazine did not improve AA hypertrophy, ET-induced contractility, ET-induced NO release, and NO sensitivity. In conclusion, blockade of the local action of ANG II improved endothelial function in AAs, a mechanism that is likely to contribute to the beneficial effects of AT1aR antagonism during the recovery of renal function after long-term NOS inhibition in rats.

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Long-term moderate exercise training improved functional capacity and quality of life in patients with stable chronic heart failure

Evidence-based Healthcare ◽

10.1054/ebhc.1999.0214 ◽

1999 ◽

Vol 3 (2) ◽

pp. 39

Author(s):

Catherine Demers ◽

Robert S. McKelvie

Keyword(s):

Quality Of Life ◽

Heart Failure ◽

Chronic Heart Failure ◽

Exercise Training ◽

Functional Capacity ◽

Moderate Exercise ◽

Moderate Exercise Training

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Effect of long-term moderate exercise training on macrophage nitric oxide and cytokine production in mice.

Exercise Science ◽

10.15857/ksep.2009.18.2.203 ◽

2009 ◽

Vol 18 (2) ◽

pp. 203-212 ◽

Cited By ~ 1

Author(s):

Wanglok Lee ◽

JongKui Jun ◽

Heegeun Park ◽

Deogjo Jung

Keyword(s):

Nitric Oxide ◽

Exercise Training ◽

Cytokine Production ◽

Moderate Exercise ◽

Moderate Exercise Training

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Secukinumab Attenuates Neuroinflammation and Neurobehavior Defect via PKCβ /ERK/NF-κB Pathway in a Rat Model of GMH

10.21203/rs.3.rs-957577/v1 ◽

2021 ◽

Author(s):

Shengpeng Liu ◽

Shuixiang Deng ◽

Yan Ding ◽

Jerry J. Flores ◽

Xiaoli Zhang ◽

...

Keyword(s):

Neurological Deficits ◽

Clinical Event ◽

Sprague Dawley ◽

Neurological Outcomes ◽

Beneficial Effects ◽

Rat Pups ◽

Tnf Α ◽

Short And Long Term ◽

Underlying Mechanisms

Abstract AimsGerminal matrix hemorrhage (GMH) is a disastrous clinical event for newborns. Neuroinflammation plays an important role in the development of neurological deficits after GMH. The purpose of this study is to investigate the anti-inflammatory role of secukinumab after GMH and its underlying mechanisms involving PKCβ/ERK/NF-κB signaling pathway.MethodsA total of 154 Sprague-Dawley P7 rat pups were used. GMH was induced by intraparenchymal injection of bacterial collagenase. Secukinumab was administered intranasally post-GMH. PKCβ activator PMA and p-ERK activator Ceramide C6 were administered intracerebroventricularly at 24h prior to GMH induction, respectively. Neurobehavioral tests, Western blot and immunohistochemistry were used to evaluate the efficacy of secukinumab in both short-term and long-term studies.ResultsEndogenous IL-17A, IL-17RA, PKCβ and p-ERK were increased after GMH. Secukinumab treatment improved short- and long-term neurological outcomes, reduced the expression of MPO and Iba-1 in the perihematoma area, and inhibited the expression of proinflammatory factors, such as NF-κB, IL-1β, TNF-α and IL-6. Additionally, PMA and ceramide C6 abolished the beneficial effects of secukinumab. ConclusionSecukinumab treatment suppressed neuroinflammation and attenuated neurological deficits after GMH, which was mediated through the downregulation of the PKCβ/ERK/NF-κB pathway. Secukinumab treatment may provide a promising therapeutic strategy for GMH patients.

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Effects of acute exhaustive exercise and long-term moderate exercise training on splenocyte immunocompetence in mice

Exercise Science ◽

10.15857/ksep.2009.18.4.467 ◽

2009 ◽

Vol 18 (4) ◽

pp. 467-474 ◽

Cited By ~ 2

Author(s):

Wanglok Lee ◽

Heegeun Park ◽

김명화 ◽

윤아람 ◽

권순미 ◽

...

Keyword(s):

Exercise Training ◽

Exhaustive Exercise ◽

Moderate Exercise ◽

Moderate Exercise Training

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Role of lung macrophages on susceptibility to respiratory infection following short-term moderate exercise training

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00274.2004 ◽

2004 ◽

Vol 287 (6) ◽

pp. R1354-R1358 ◽

Cited By ~ 29

Author(s):

E. A. Murphy ◽

J. M. Davis ◽

A. S. Brown ◽

M. D. Carmichael ◽

N. Van Rooijen ◽

...

Keyword(s):

Exercise Training ◽

Respiratory Infection ◽

Symptom Severity ◽

Moderate Exercise ◽

Upper Respiratory Tract ◽

Short Term ◽

Beneficial Effects ◽

Lung Macrophages ◽

Moderate Exercise Training

Moderate exercise training is associated with a decreased risk for upper respiratory tract infection in human and animal studies, but the mechanisms have not been elucidated. Lung macrophages play an important role in resistance to respiratory infection, and moderate exercise can enhance macrophage antiviral resistance, but no studies have directly tested the role of lung macrophages in this response. This study tested the effect of lung macrophage depletion on susceptibility to infection following short-term moderate exercise training. Mice were assigned to one of four groups: exercise (Ex) and resting controls (Con) with and without clodronate encapsulated liposomes (CL2MDP-lip). Ex mice ran for 1 h on a treadmill for 6 days at 36 m/min, 8% grade. Fifteen minutes following exercise or rest on the last day of training, mice were intranasally inoculated with a standardized dose of herpes simplex virus type 1. Clodronate (Ex-CL2MDP-lip and Con-CL2MDP-lip) or PBS liposomes (Ex-PBS-lip and Con-PBS-lip) (100 μl) were intranasally administered following exercise or rest on the 4th day of training and again on the 4th day postinfection. Morbidity, mortality, and symptom severity were monitored for 21 days. Exercise decreased morbidity by 36%, mortality by 61%, and symptom severity score on days 5–7 ( P < 0.05). Depletion of lung macrophages negated the beneficial effects of moderate exercise. This was indicated by no differences between Ex-CL2MDP-lip and Con-PBS-lip in morbidity (89 vs. 95%), mortality (79 vs. 95%), or symptom severity. Results indicate that lung macrophages play an important role in mediating the beneficial effects of moderate exercise on susceptibility to respiratory infection.

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