A dual nociceptin and mu opioid receptor agonist exhibited robust antinociceptive effect with decreased side effects.

The compelling demand of a consummate analgesic medication without addiction is rising due to the clinical mistreatment. Additionally, the series of severe untoward effects usually deterred the utilization while coping with serious pain. As a possible turning point, we revealed that compound 14 is a dual agonist of mu opioid receptor (MOR) and nociceptin-orphanin FQ opioid peptide (NOP) receptor in this study. More importantly, compound 14 achieves pain relieving at very small doses, meanwhile, reduces several unwanted side effects such as constipation, reward, tolerance and withdrawal effects. Here, we evaluated the antinociception and side effects of this novel compound from wild type and humanized mice to further develop a safer prescription analgesic drug.

Expression and distribution of S-100, CD83, and costimulatory molecules (CD80 and CD86) in tissues of thyroid papillary carcinoma.

A higher expression of S-100 in tissue of thyroid papillary carcinoma (TPC) vs. thyroid follicular adenoma (TFA) (p < .001) was observed as well as a higher expression of CD83 in the peri-cancerous tissues vs. TFA (p < .001), oppositely, CD83 was negative in the cancerous net. TPC showed greater decreases in levels of CD80 and CD86 than did the TFA. These findings suggest that impaired immune function, absence of CD83-positive mature and activated dendritic cells in cancer nodules may have a role in the pathogenesis of TPC. The low expression of CD80 and CD86 in TPC may help them evade the immune system.

Study on immune function of dendritic cells in patients with esophageal carcinoma.

AIM: To investigate the immune function of dendritic cells from both peripheral blood and operated tissues of esophageal carcinoma patients in order to find the relationship between the immune function of dendritic cells and the pathogenesis of esophageal carcinoma. METHODS: The expression of CD83, CD80, and CD86 on the surface of dendritic cells cultured from the peripheral blood of patients was detected compared with that from health donors using flow cytometry. The ability of dendritic cells to induce T lymphocyte proliferation was evaluated by a liquid scintillation counter. The expression of CD80, CD86, CD83, and S-100 proteins was assessed in esophageal carcinoma tissues using immunohistochemical method. RESULTS: Compared with those from healthy donors, dendritic cells cultured from the peripheral blood of patients expressed lower CD80 and CD86. Furthermore, the ability of dendritic cells in patients to induce T lymphocyte proliferation was significantly lower than that of the control group. Compared with the control group, the positive expression ratio and frequencies of CD80, CD86, and S-100 in esophageal carcinoma tissues were significantly down regulated. The expression of CD83 was up-regulated in the pericancerous tissues, but no expression was found in the cancerous nodules. CONCLUSION: The impaired immune function and the decreased number of dendritic cells cause pathogenesis and progression of esophageal carcinoma.

Event-related potentials P300 in type 2 diabetes mellitus.

OBJECTIVE: To investigate event-related potentials (ERP) P(300) in patients with type 2 diabetes mellitus (DM) for early detection of the abnormalities in cognitive function and studying the related factors. METHODS: With the assistance of Nicolet Vinking IV equipment, ERP (P(300)) were tested in 30 type 2 diabetic patients and 30 healthy subjects matched for age, gender, and education background, and the the results were analyzed statistically. The relationships of each ERP parameter with glucose hemoglobin (GHb) and blood lipid levels and renal function were analyzed. RESULTS: No significant difference was found in P(300) latencies in the control group irrespective of the gender and education (P > 0.05), while the latencies were significantly prolonged (P < 0.01) and the amplitudes decreased (P < 0.05) in diabetic patients. It was found that P(300) correlated with glucose hemoglobin (GHb) and blood lipid levels (P < 0.05). CONCLUSION: ERP test is useful for early detection of cognition dysfunction in DM cases, helping to timely identify diabetic patients with potential dementia.

In vitro antigen-specific cytotoxic T cell response against esophageal carcinoma cells induced by HPV18E7-transfected dendritic cells.

Human Papillomavirus (HPV)-associated esophageal carcinoma (EC) is a high incidence tumor worldwide. Dendritic cell (DC)-based tumor vaccine is considered an alternative therapy to treat EC. Here we developed a DC-based vaccine by transfecting cord blood CD34+ stem cell-derived DC with HPV18E7 gene, observed its biological characteristics and the antigen-specific T-cell cytotoxicity on EC cells induced by HPV18E7-DC in vitro. Our results showed that 1) HPV18E7 gene transfer did not change the typical morphology of mature DC, 2) the representative phenotypes of mature DC (CD80, CD86, and CD83) were highly expressed in HPV18E7- DC (81.6%, 80.5%, and 86.6%, respectively), 3) the expression level of 18E7 protein in HPV18E7-DC was 47.5%, and 4) the specific cytotoxicity against EC cells was significantly higher than that in controls (p<0.01). This study indicates the possibility of a DC-based immunotherapy in HPV-associated EC.

Changes of serum and urine neutrophil gelatinase-associated lipocalin in type-2 diabetic patients with nephropathy: one year observational follow-up study.

We initiated the present work to explore whether neutrophil gelatinase-associated lipocalin (NGAL) could be used to predict the progression of diabetic nephropathy in type-2 diabetic patients. Seventy-four type-2 diabetic patients were divided into normo-, micro- and macro-albuminuria groups according to their 24 h-urinary albumin excreting rate. Serum and urine NGAL, and other clinical parameters were detected. Patients were followed and measurements were repeated 1 year later. An increased tendency of urine NGAL and a decreased tendency of serum NGAL were detected, from normo-albuminuria group to macro-albuminuria group. Serum NGAL was found to rise after follow-up. Moreover, urine NGAL was found to be correlated positively with cystatin C, urea nitrogen, and serum creatinine (SCr), and inversely with glomerular filtration rate (GFR), while serum NGAL correlated negatively with cystatin C and urea nitrogen, at both baseline and follow-up levels. The results indicate that NGAL correlates closely with renal function. Both serum and urine NGAL are sensitive for predicting the progression of type-2 diabetic nephropathy but they may change differently. Serum NGAL may be more useful in early detection and urine NGAL may be more meaningful in renal function assessment.

Heterogeneity in mitotic activity and telomere length implies an important role of young islets in the maintenance of islet mass in the adult pancreas.

Understanding the mechanisms of beta-cell dynamics in postnatal animals is central to cure diabetes. A major obstacle in evaluating the status of pancreatic cells is the lack of surface markers. Here we performed quantitative measurements of two internal markers to follow the developmental history of islets. One marker, cell-cycle activity, was established by measuring expression of Ki67 and the incorporation of 5-bromodeoxyuridine. The other marker, the aging process, was delineated by the determination of telomere length. Moreover, islet neogenesis, possibly from ductal precursors, was monitored by pancreatic duct labeling with an enhanced green fluorescence protein (EGFP) transgene. We found that islets from younger animals, on average, expressed higher Ki67 transcripts, displayed elevated 5-bromodeoxyuridine incorporation, and had longer telomeres. However, significant heterogeneity of these parameters was observed among islets from the same mouse. In contrast, the levels of proinsulin-1 transcripts in islets of different ages did not change significantly. Moreover, mitotic activities correlated significantly with telomere lengths of individual islets. Lastly, after 5.5 d pancreatic duct labeling, a few EGFP-positive islets could be identified in neonatal but not from adult pancreases. Compared with unlabeled control islets, EGFP-positive islets had higher mitotic activities and longer telomeres. The results suggest that islets are born at different time points during the embryonic and neonatal stages and imply that young islets might play an important role in the maintenance of islet mass in the adult pancreas.