Introduction: Inflammation has a crucial role in the progression of cardiovascular disease in diabetes. Tumour necrosis factor-α (TNF-α) as an inflammatory marker induces angiotensin II (Ang II) related hypertension pathway in diabetic patients. Gut modulation via prebiotics may ameliorate hypertension caused by inflammation. The aim of this study was to investigate the role of sodium butyrate (NaBut) and inulin supplements on inflammatory and oxidative stress parameters in type 2 diabetic patients.
Methods: In this clinical trial, 60 overweight and obese diabetic patients were recruited and randomly allocated into four groups. The groups received, respectively, 600 mg/d NaBut (group A), 10 g/d inulin powder (group B), both inulin and NaBut (group C), or placebo (group D) for 45 consecutive days. Blood and stool samples were collected at baseline and after intervention. Quantitative real-time PCR analysis targeting the 16S rRNA gene of Akkermansia muciniphila was done. We assessed the TNF-α mRNA expression and the serum levels of the high sensitive C-reactive protein (hs-CRP) and malondialdehyde (MDA).
Results: There was a significant increase in A. muciniphila percent change in inulin and butyrate supplemented groups (P < 0.05). Furthermore, significant decrease was seen in TNF-α mRNA expression in group A (fold change 0.88 ± 0.16, P< 0.05), group B (fold change 0.75 ± 0.18, P < 0.05) and group C (fold change 0.91 ± 0.32, P < 0.05). Also hs-CRP, MDA and diastolic blood pressure levels decreased significantly in these groups (P < 0.05).
Conclusion: Intervention had significant effects on inflammatory and oxidative stress parameters and led to improvement of hypertension. However, further investigations are needed to make concise conclusions.
Natural killer (NK) cells are immune cells that have attracted signi cant attention due to their cytotoxic properties. They are believed to be highly effective in cancer therapy. In this study, anti-KIR2DL4 (Killer cell Immunoglobulin like Receptor, 2 Ig Domains and Long cytoplasmic tail 4) was used to stimulate the NK-92 activator receptor to increase their cytotoxicity on breast cancer cell lines. Unstimulated and stimulated NK-92 cells (sNK-92) were cocultured with breast cancer (MCF-7 and SK-BR-3) and normal breast (MCF-12A) cell lines at 1:1, 1:5, and 1:10 (Target: Effector) ratios. The most effective cell cytotoxicity ratio (1:10) was used in the immunostaining and western blot assays to evaluate apoptosis pathway proteins. The sNK-92 cells showed higher cytotoxic activity on breast cancer cells than NK-92 cells. sNK-92 cells had a selective signi cant cytotoxicity effect on MCF-7 and SK-BR-3 cells but not MCF-12A cells. While sNK-92 cells were effective at all cell concentrations, they were most effective at a 1:10 ratio. Immunostaining and western blots showed signi cantly higher BAX, caspase 3, and caspase 9 protein levels in all breast cancer cell groups cocultured with sNK-92 than with NK-92 cells. NK-92 cells stimulated with KIR2DL4 showed elevated cytotoxic activity. The cytotoxic activity of sNK-92 cells on breast cancer cells is via apoptosis pathways. However, their effect on normal breast cells is limited. While the obtained data contains only basic information, additional clinical studies are needed to provide a basis for a new treatment model.
Recent increase in the interest in stem and progenitor cells may be attributed to their behavioural characteristics. A consensus has been reached that embryonic or adult stem cells have therapeutic potential. As cardiovascular health issues are still the major culprits in many developed countries, stem and progenitor cell driven approaches may give the clinicians a new arsenal to tackle many significant health issues. However, stem and progenitor cell mediated cardiovascular regeneration can be achieved via complex and dynamic molecular mechanisms involving a variety of cells, growth factors, cytokines, and genes. Functional contributions of transplanted cells on target organs and their survival are still critical problems waiting to be resolved. Moreover, the regeneration of contracting myocardial tissue has controversial results in human trials. Thus, moderately favourable clinical results should be interpreted carefully. Determining the behavioural programs, genetic and transcriptional control of stem cells, mechanisms that determine cell fate, and functional characteristics are the primary targets. In addition, ensuring the long-term follow-up of cells with efficient imaging techniques in human clinical studies may provide a resurgence of the initial enthusiasm, which has faded over time. Here, we provide a brief historical perspective on stem cell driven cardiac regeneration and discuss cardiac and vascular repair in the context of translational science.
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