Inonotus sanghuang Polyphenols Attenuate Inflammatory Response Via Modulating the Crosstalk Between Macrophages and Adipocytes

Aims: Obesity is characterized as a chronic state of low-grade inflammation with progressive immune cell infiltration into adipose tissue. Adipose tissue macrophages play a critical role in the establishment of chronic inflammatory states and metabolic dysfunctions. Inonotus (I.) sanghuang and its extract polyphenols exhibit anti-carcinogenesis, anti-inflammatory, and anti-oxidant activities. However, the action of I. sanghuang polyphenols in obesity-related inflammation has not been reported. The aim of this study was to explore the anti-inflammatory action of polyphenols from I. sanghuang extract (ISE) in macrophages and the interaction between macrophages and adipocytes.Materials and Methods: RAW264.7 macrophages were stimulated with LPS or conditioned medium of hypertrophied 3T3-L1 adipocytes or cocultured with differentiated adipocytes in the presence of different doses of ISE. The inflammatory cytokines were evaluated by ELISA, the MAPK, NF-κB, and IL-6/STAT3 signals were determined by immunoblotting, and the migrated function of macrophages was determined by migration assay.Results: ISE suppressed the inflammatory mediators including NO, TNF-α, IL-6, and MCP-1 induced by either LPS or conditioned medium derived from 3T3-L1 adipocytes. ISE also decreased the production of these inflammatory mediators in cocultures of 3T3-L1 adipocytes and RAW264.7 macrophages. Furthermore, ISE blocked RAW264.7 macrophages migration toward 3T3-L1 adipocytes in cocultures. Finally, this effect of ISE might be mediated via inhibiting ERK, p38, and STAT3 activation.Conclusions: Our findings indicate the possibility that ISE suppresses the interaction between macrophages and adipocytes, attenuates chronic inflammation in adipose tissue and improves obesity-related insulin resistance and complication, suggesting that ISE might be a valuable medicinal food effective in improving insulin resistance and metabolic syndrome

Berberine ameliorates diabetic nephropathy by inhibiting TLR4/NF-κB pathway

Abstract Background Diabetic nephropathy (DN) is the leading cause of end-stage renal failure, contributing to severe morbidity and mortality in diabetic patients. Berberine (BBR) has been well characterized to exert renoprotective effects in DN progression. However, the action mechanism of BBR in DN remains to be fully understood. Methods The DN rat model was generated by intraperitoneal injection of streptozotocin (STZ, 65 mg/kg body weight) while 30 mM high glucose (HG)-treated podocytes were used as an in vitro DN model. The fasting blood glucose level and ratio of kidney weight to body weight were measured after BBR treatment (50, 100, or 200 mg/kg) in STZ-induced DN rats. The renal injury parameters including 24-h urinary protein, blood urea nitrogen and serum creatinine were assessed. qRT-PCR was performed to detect the transcript amounts of inflammatory factors. The concentrations of inflammatory factors were evaluated by ELISA kits. Western blot analysis was conducted to measure the amounts of TLR4/NF-κB-related proteins. The apoptotic rate of podocytes was analyzed by flow cytometry using Annexin V/propidium iodide. Results Berberine reduced renal injury in STZ-induced DN rat model, as evidenced by the decrease in fasting blood glucose, ratio of kidney weight to body weight, 24-h urinary protein, serum creatinine, and blood urine nitrogen. BBR attenuated the systemic and renal cortex inflammatory response and inhibited TLR4/NF-κB pathway in STZ-induced DN rats and HG-induced podocytes. Also, HG-induced apoptosis of podocytes was lowered by BBR administration. Furthermore, blockade of TLR4/NF-κB pathway by resatorvid (TAK-242) or pyrrolidine dithiocarbamate aggravated the inhibitory effect of BBR on HG-induced inflammatory response and apoptosis in podocytes. Conclusions Berberine ameliorated DN through relieving STZ-induced renal injury, inflammatory response, and podocyte HG-induced apoptosis via inactivating TLR4/NF-κB pathway

Original Article Establishment of pancreatic cancer stem cells by flow cytometry and their biological characteristics

Abstract: To investigate the method of separating human pancreatic cancer stem cells by Hoechst 33342 labeled flow cytometry and to analyze the biological properties of pancreatic cancer stem cells. The human pancreatic cancer cell line PC-3 was divided into SP and non-SP cells by flow cytometry. The number of two cell clone spheres and nude mice tumor formation rates were compared by cultivating in serum-free medium; The expression of CD133, Nestin mRNA and protein was analyzed by real-time fluorescence quantitative PCR and Western blot; The expression of two cell drug resistance genes (MDR1, ABCG2, ABCA2 and MRP1) was analyzed by real time fluorescent quantitative PCR. The number of the cloned spheres in SP cells in serum-free medium was significantly higher than that of non-SP cells (P<0.05). The incidence of SP cells in the tumor of immunodeficiency nude mice was significantly higher than that of non-SP cells, and the difference was statistically significant (P<0.05). Real-time fluorescence quantitative PCR analysis showed that the expression of CD133 and Nestin mRNA in SP cells was significantly higher than those of non-SP cells, and the expression of CD133 and Nestin protein in SP cells was also significantly higher than those of non-SP cells (P<0.05). In conclusion, SP side population pancreatic cancer cells by Hoechst 33342 separation have the stem cell characteristics, higher tumor formation rate and higher drug resistance, which may be related to chemotherapy resistance

Safety and Efficacy of High Versus Standard Starting Doses of Insulin Glargine in Overweight and Obese Chinese Individuals with Type 2 Diabetes Mellitus Inadequately Controlled on Oral Antidiabetic Medications (Beyond VII: Study Protocol for a Randomized Controlled Trial

<p><b> </b></p> <p><b>Article full text</b></p><p><br></p><p>The full text of this article can be found here<b>. </b><a href="https://link.springer.com/article/10.1007/s12325-018-0717-x">https://link.springer.com/article/10.1007/s12325-018-0717-x</a></p><p></p><p><br></p><p><b>Provide enhanced content for this article</b></p><p><br></p><p>If you are an author of this publication and would like to provide additional enhanced content for your article then please contact <a href="http://www.medengine.com/Redeem/”mailto:[email protected]”"><b>[email protected]</b></a>.</p><p><br></p><p>The journal offers a range of additional features designed to increase visibility and readership. All features will be thoroughly peer reviewed to ensure the content is of the highest scientific standard and all features are marked as ‘peer reviewed’ to ensure readers are aware that the content has been reviewed to the same level as the articles they are being presented alongside. Moreover, all sponsorship and disclosure information is included to provide complete transparency and adherence to good publication practices. This ensures that however the content is reached the reader has a full understanding of its origin. No fees are charged for hosting additional open access content.</p><p><br></p><p>Other enhanced features include, but are not limited to:</p><p><br></p><p>• Slide decks</p><p>• Videos and animations</p><p>• Audio abstracts</p><p> </p><p>• Audio slides</p> <p><b> </b></p

A comparison of daily glucose fluctuation among GCK-MODY and type 2 diabetes using continuous glucose monitoring technology

   Glucokinase variant-induced maturity-onset diabetes of the young (GCK-MODY) exhibits the unique clinical features of mild fasting hyperglycaemia. However, formal studies of its glucose excursion pattern in daily life in comparison with those with or without other types of diabetes are lacking. We conducted a case-control study including 25 patients with GCK-MODY, 25 A1c-matched, drug naive patients with type 2 diabetes (T2DM) and 25 age-, BMI- and sex-matched subjects with normal glucose tolerance (NGT). All the subjects wore flash glucose monitoring (FGM) sensors for 2 weeks, and glucose readings were masked. Glucose excursion was significantly lower in the GCK-MODY than that in A1c-matched T2DM during the daytime, but was similar during the nighttime. The daytime coefficient of variation [CV] driven by postprandial glucose could separate GCK-MODY from well-controlled T2DM, but the nighttime CV could not. In discriminating between GCK-MODY and T2DM, the area under the curve (AUC) of the CV was 0.875. However, in GCK-MODY and NGT subjects, the CVs were similar at 24h, whereas the other four excursion parameters were significantly higher in GCK-MODY than those in NGT subjects. FGM confirmed the stability and mildness of hyperglycemia in GCK-MODY patients. Postprandial regulation is a key driver of the difference in excursion between GCK-MODY and T2DM.</p