The neuroprotective effects of human bone marrow mesenchymal stem cells are dose-dependent in TNBS colitis

The incidence of inflammatory bowel diseases (IBD) is increasing worldwide with patients experiencing severe impacts on their quality of life. It is well accepted that intestinal inflammation associates with extensive damage to the enteric nervous system (ENS), which intrinsically innervates the gastrointestinal tract and regulates all gut functions. Hence, treatments targeting the enteric neurons are plausible for alleviating IBD and associated complications. Mesenchymal stem cells (MSCs) are gaining wide recognition as a potential therapy for many diseases due to their immunomodulatory and neuroprotective qualities. However, there is a large discrepancy regarding appropriate cell doses used in both clinical trials and experimental models of disease. We have previously demonstrated that human bone marrow MSCs exhibit neuroprotective and anti-inflammatory effects in a Guinea-pig model of 2,4,6-trinitrobenzene-sulfonate (TNBS)-induced colitis; but an investigation into whether this response is dose-dependent has not been conducted. Methods: Hartley Guinea-pigs were administered TNBS or sham treatment intra-rectally. Animals in the MSC treatment groups received either 1 × 10 5 , 1 × 10 6 or 3 × 10 6 MSCs by enema 3 hours after induction of colitis. Colon tissues were collected 72 hours after TNBS administration to assess the effects of MSC treatments on the level of inflammation and damage to the ENS by immunohistochemical and histological analyses. Results: MSCs administered at a low dose, 1 × 10 5 cells, had little or no effect on the level of immune cell infiltrate and damage to the colonic innervation was similar to the TNBS group. Treatment with 1 × 10 6 MSCs decreased the quantity of immune infiltrate and damage to nerve processes in the colonic wall, prevented myenteric neuronal loss and changes in neuronal subpopulations. Treatment with 3 × 10 6 MSCs had similar effects to 1 × 10 6 MSC treatments. Conclusions: The neuroprotective effect of MSCs in TNBS colitis is dose-dependent. Increasing doses higher than 1 × 10 6 MSCs demonstrates no further therapeutic benefit than 1 × 10 6 MSCs in preventing enteric neuropathy associated with intestinal inflammation. Furthermore, we have established an optimal dose of MSCs for future studies investigating intestinal inflammation, the enteric neurons and stem cell therapy in this model

Human adult stem cells derived from adipose tissue and bone marrow attenuate enteric neuropathy in the guinea-pig model of acute colitis

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Neuroprotective potential of mesenchymal stem cell-based therapy in acute stages of TNBS-induced colitis in Guinea-pigs

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Allogeneic Guinea pig mesenchymal stem cells ameliorate neurological changes in experimental colitis

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Combination of taurine and black pepper extract as a treatment for cardiovascular and coronary artery diseases

The shift in modern dietary regimens to “Western style” and sedentary lifestyles are believed to be partly responsible for the increase in the global burden of cardiovascular diseases. Natural products have been used throughout human history as treatments for a plethora of pathological conditions. Taurine and, more recently, black pepper have gained attention for their beneficial health effects while remaining non-toxic even when ingested in excess. Taurine, black pepper, and the major terpene constituents found in black pepper (i.e., β-caryophyllene; α-pinene; β-pinene; α-humulene; limonene; and sabinene) that are present in PhytoCann BP® have been shown to have cardioprotective effects based on anti-inflammatory, antioxidative, anti-hypertensive and anti-atherosclerotic mechanisms. This comprehensive review of the literature focuses on determining whether the combination of taurine and black pepper extract is an effective natural treatment for reducing cardiovascular diseases risk factors (i.e., hypertension and hyperhomocysteinemia) and for driving anti-inflammatory, antioxidative and anti-atherosclerotic mechanisms to combat coronary artery disease, heart failure, myocardial infarction, and atherosclerotic disease

Oxidative Stress and Neural Dysfunction in Gastrointestinal Diseases: Can Stem Cells Offer a Solution?

Oxidative stress is involved in many gastrointestinal (GI) disorders as either the primary pathogenesis (radiation, chemotherapy, toxicity, ischemia-reperfusion) or a secondary driving force of disease progression (inflammation and diabetes). The GI tract is innervated intrinsically by the enteric nervous system (ENS) with a diverse role in maintaining gut homeostasis and GI motility. Complications in the physiological functioning of the ENS results in GI dysfunction that can result in debilitating sequelae from dysmotility greatly impacting quality of life and leading to potentially fatal complications. Therapeutics to remedy either oxidative stress or enteric neuronal dysfunction are severely limited, resulting in a critical gap in clinical care for GI disease and neurointestinal complications. Stem cell therapies have shown great promise in the treatment of several gut disorders via mechanisms including cell regeneration, anti-inflammatory activity, providing trophic support, and emerging evidence of antioxidant and neuroprotective functions. The potential of mesenchymal stem cell (MSC) therapies and recent evidence of their antioxidant and neuroprotective activity in several GI conditions are discussed. Finally, future therapeutic aspects of stem cell-based tools for combatting oxidative stress and enteric neuropathies in GI disease are considered

Altered stress hormone response following acute exercise during prostate cancer treatment

Exercise training reduces the side effects of cancer treatments; however, the stress hormone response to acute exercise during prostate cancer (PCa) treatment is unclear. The study purpose was to examine the effects of acute exercise on circulating cortisol, epinephrine (Epi), and norepinephrine (NE) concentrations during PCa treatment with and without androgen deprivation therapy (ADT). Men with PCa (n = 11), with PCa on ADT (n = 11), and with non-cancer controls (n = 8) had blood samples for stress hormones collected before and immediately (0 hour), 2 hours, and 24 hours after 45 minutes of intermittent cycling at 60% of peak wattage. NE increased by 385% (P < .001) at 0 hour and remained elevated at 2 hours (P < .05) with no group differences. Overall, cortisol significantly increased at 0 hour (36%, P < .012) and then significantly decreased below baseline at 2 hours (-24%, P < .001) before returning to resting levels at 24 hours. Cortisol levels during ADT were 32% lower than PCa (P = .006) with no differences vs controls. Epi increased immediately after exercise more in controls (817%, P < .001) than with ADT (700%) and PCa (333%) patients, and both cancer groups' absolute levels were attenuated relative to controls (ADT: -54%, PCa: -52%, P = .004). Compared with age-matched controls, PCa and ADT patients exhibited similar stress hormone responses with acute exercise for NE and cortisol but an attenuated EPI response that suggests altered adrenal function. Future studies should examine the physical stress of multiple exercise bouts to verify these findings and to explore the functional hormonal effects, such as immune and metabolic responses, during cancer treatment

Oxaliplatin Treatment Alters Systemic Immune Responses

Purpose. Oxaliplatin is a platinum-based chemotherapeutic agent demonstrating significant antitumor efficacy. Unlike conventional anticancer agents which are immunosuppressive, oxaliplatin has the capacity to stimulate immunological effects in response to the presentation of damage associated molecular patterns (DAMPs) elicited upon cell death. However, the effects of oxaliplatin treatment on systemic immune responses remain largely unknown. Aims of this study were to investigate the effects of oxaliplatin treatment on the proportions of (1) splenic T cells, B cells, macrophages, pro-/anti-inflammatory cytokines, gene expression of splenic cytokines, chemokines, and mediators; (2) double-positive and single-positive CD4+ and CD8+ T thymocytes; (3) bone-marrow hematopoietic stem and progenitor cells. Methods. Male BALB/c mice received intraperitoneal injections of oxaliplatin (3mg/kg/d) or sterile water tri-weekly for 2 weeks. Leukocyte populations within the spleen, thymus, and bone-marrow were assessed using flow cytometry. RT-PCR was performed to characterise changes in splenic inflammation-associated genes. Results. Oxaliplatin treatment reduced spleen size and cellularity (CD45+ cells), increased the proportion of CD4+, CD8+, and Treg cells, and elevated TNF-α expression. Oxaliplatin was selectively cytotoxic to B cells but had no effect on splenic macrophages. Oxaliplatin treatment altered the gene expression of several cytokines, chemokines, and cell mediators. Oxaliplatin did not deplete double-positive thymocytes but increased the single-positive CD8+ subset. There was also an increase in activated (CD69+) CD8+ T cells. Bone-marrow hematopoietic progenitor pool was demonstrably normal following oxaliplatin treatment when compared to the vehicle-treated cohort. Conclusion. Oxaliplatin does not cause systemic immunosuppression and, instead, has the capacity to induce beneficial antitumor immune responses

Maximal exercise increases mucosal associated invariant T cell frequency and number in healthy young men

Mucosal associated invariant T (MAIT) cells have properties of the innate and acquired immune systems. While the response to vigorous exercise has been established for most leukocytes, MAIT cells have not been investigated. Therefore, the purpose was to determine if MAIT cell lymphocytosis occurs with acute maximal aerobic exercise and if this response is influenced by exercise duration, cardiovascular fitness, or body composition