Correction of Hyperglycemia in Diabetic Rats With the Use of Microencapsulated Young Market Pig Islets.

OBJECTIVE: The aim of this work was to investigate the transplantation efficacy of microencapsulated young market pig islets in a diabetic rat model. METHODS: Islets were isolated and purified from young market pigs obtained from a local slaughterhouse. The islets were encapsulated in barium alginate and subjected to a glucose-induced insulin release functional assay in culture. Microencapsulated islets were transplanted into diabetic Sprague-Dawley rats and removed after 30 days for histologic examination. RESULTS: The mean islet equivalent (IEQ) yield per gram of digested tissue was 3,125 ± 617 IEQ/g after isolation and 2,618 ± 917 IEQ/g after purification, respectively. Host rats' blood glucose concentrations normalized (from 22.3 ± 2.7 mmol/L to 5.1 ± 0.67 mmol/L) following encapsulated islet transplantation. After graft removal, hyperglycemia recurred in the rats, indicating that the grafts were responsible for maintaining euglycemia. Histology revealed viable islets in the capsules 30 days after graft removal. Immunolabeling of insulin verified that ß-cells within the capsules remained well granulated. No fibrosis or immune cells were found in histopathology. CONCLUSIONS: Barium alginate encapsulation of young market pig islets can normalize glucose regulation in diabetic rats without fibrosis or an immunologic response.

Disrupted Brain Connectivity Patterns in Patients with Type 2 Diabetes.

BACKGROUND AND PURPOSE: Type 2 diabetes is associated with an increased risk of dementia. This study investigated the global connectivity patterns in the brains of patients with type 2 diabetes by using a functional MR imaging technique. MATERIALS AND METHODS: Forty patients and 43 age-, sex-, and education-matched healthy controls underwent resting-state functional imaging in a 3T MR imaging unit. Degree centrality, a commonly used measurement of global connectivity, was computed for a full-brain exploration of the regions influenced by type 2 diabetes. We then examined the functional connectivity of each region by using the seed-based approach. Finally, voxelwise correlation analyses were performed to explore the relationship among the connectivity changes, cognitive performance, and diabetes-related variables. RESULTS: Patients exhibited decreased degree centrality in the left lingual gyrus and increased centrality in the right insula and dorsal anterior cingulate cortex (corrected P < .05). The occipital network anchored in the lingual gyrus showed extensively reduced connectivity, while the network connectivity of the insula and cingulate cortex (mostly included in the salience network) was significantly elevated (corrected P < .05). Correlational analyses revealed that in the diabetic group, impaired visual memory and executive function performance were correlated with occipital hypoconnectivity, while higher fasting plasma glucose levels and better executive functioning were related to anterior cingulate cortex hyperconnectivity (all corrected P values < .05). Similar effects were not detected in the controls. CONCLUSIONS: This preliminary study shows that network connectivity is altered in patients with type 2 diabetes, which may provide critical insight into the neural substrate of diabetes-related cognitive decline.

Optimization of pyrethroid and repellent on fabrics against Stegomyia albopicta (=Aedes albopictus) using a microencapsulation technique.

A new approach employing a combination of pyrethroid and repellent is proposed to improve the protective efficacy of conventional pyrethroid-treated fabrics against mosquito vectors. In this context, the insecticidal and repellent efficacies of commonly used pyrethroids and repellents were evaluated by cone tests and arm-in-cage tests against Stegomyia albopicta (=Aedes albopictus) (Diptera: Culicidae). At concentrations of LD50 (estimated for pyrethroid) or ED50 (estimated for repellent), respectively, the knock-down effects of the pyrethroids or repellents were further compared. The results obtained indicated that deltamethrin and DEET were relatively more effective and thus these were selected for further study. Synergistic interaction was observed between deltamethrin and DEET at the ratios of 5 : 1, 2 : 1, 1 : 1 and 1 : 2 (but not 1 : 5). An optimal mixing ratio of 7 : 5 was then microencapsulated and adhered to fabrics using a fixing agent. Fabrics impregnated by microencapsulated mixtures gained extended washing durability compared with those treated with a conventional dipping method. Results indicated that this approach represents a promising method for the future impregnation of bednet, curtain and combat uniform materials.

Expression pattern of tumour-associated antigens in hepatocellular carcinoma: association with immune infiltration and disease progression.

BACKGROUND: The distinct expression pattern of tumour-associated antigens (TAAs) might be a critical reason for the inefficacy of immunity-based treatments and heterogeneous postsurgical recovery in patients with solid tumours, including hepatocellular carcinoma (HCC). However, little is known about the clinical value of the coexpression patterns of multiple TAAs. METHODS: We determined the expression of multiple TAAs with identified immunogenicity (GPC3, AFP, SSX-2, NY-ESO-1, EpCAM, midkine) and the density of tumour-infiltrating immune cells by immunohistochemistry in a panel of 362 primary HCC patients. We evaluated the association between the TAAs, immune cell infiltration, clinicopathological parameters, and prognosis. RESULTS: Patients who coexpressed more TAAs had better prognosis (P<0.00001, overall survival). The integrated pattern of TAA was associated with good differentiation and small tumour size, and with more CD57(+) natural killer and CD20(+) B-cell infiltration (P<0.05). Multivariate Cox proportional hazards analysis identified the TAA index as an independent prognostic indicator (hazard ratio 0.625; 95% confidence interval 0.467-0.837; P=0.002), and could further predict patient prognosis in collaboration with local immune infiltration. CONCLUSION: Our results could provide new evidence for the improvement of prognostic molecular signatures in HCC, and a novel rationale for patient enrolment in future immunotherapeutic trials and/or clinical treatments.

Natural products with antitumor activity from endophytic fungi.

Endophytic fungi are a seemingly inexhaustible source of novel bioactive natural products. Currently, more than 140 fungal metabolites have shown confirmed activity in tumor cell line bioassays. We present the chemical structures of these antitumor metabolites, their corresponding fungal endophytes and host plants, and the activities they exhibited, and briefly discuss some of their action mechanisms. This review emphasizes the role of endophytic fungi as an important source of leads for drug discoveries.

PI3K/Akt/mTOR pathway inhibitors in cancer: a perspective on clinical progress.

The phosphoinositide 3-kinase (PI3K)/serine-theronine protein kinase Akt (also known as protein kinase B (PKB))/mammalian target of rapamycin (mTOR) pathway is a vital transduction cascade that is connected with many essential cellular activities, such as growth and survival. Along with extensive pharmacological studies validating the therapeutic potential of targeting the PI3K/Akt/mTOR pathway for the treatment of cancer, kinase inhibitors targeting significant knots of this pathway including PI3K, Akt, mTOR, and 3-phosphoinositide-dependent protein kinase-1 (PDK-1) keep arising and entering clinical studies. Herein, we review the most up-to-date landscape on developing small-molecule kinase inhibitors targeting the PI3K/Akt/mTOR pathway, with emphasis on small-molecule inhibitors which have been progressed into clinical studies.

CK19 mRNA expression in the bone marrow of patients with esophageal squamous cell carcinoma and its clinical significance.

The 5-year survival rate in resectable patients with esophageal cancer is only 20% to 36%. Regional relapse and distant metastasis are responsible for the failure of treatment and the majority of cancer-related deaths. Earlier detection of metastases, especially micrometastases, has the potential for more accurate risk stratification in subsequent therapy decisions. No effective techniques have yet been found to detect metastases in erroneously thought to have early stage disease. This study was designed to investigate the clinical significance of bone marrow micrometastases detected by reverse transcriptase-polymerase chain reaction (RT-PCR) in patients with esophageal cancer. Expression of CK19 mRNA in the bone marrow of 61 patients with esophageal squamous cell carcinoma (ESCC) and 15 benign pulmonary and esophageal disease patients was assessed via RT-PCR. Correlation of CK19 mRNA expression to the clinicopathologic features and prognosis of the 61 patients was analyzed: 21.3% (13/61) were positive for expression of CK19 mRNA in patients with ESCC. No CK19 mRNA was detected of the 15 benign pulmonary and esophageal disease patients. CK19 mRNA expression did not correlate with the clinicopathologic features of the patients with ESCC, but patients with CK19 mRNA-positive bone marrow had earlier recurrence and shorter survival after surgery. In multivariate analysis, CK19 mRNA was found to be an independent predictor of a poor outcome. CK19 mRNA may be used as a molecular maker to detect bone marrow micrometastases in patients with ESCC and may help to select the proper therapy and predict the prognosis.