An aquaporin and an aquaglyceroporin have roles in low temperature adaptation of mosquitoes (Anopheles sinensis).

Mosquitoes (Anopheles sinensis), widely geographically distributed in Asia including China, are the primary vector of the malaria parasite Plasmodium vivax and other parasitic diseases such as Malayan filariasis. An. sinensis can survive through low winter temperatures. Aquaporin channels are found in all life forms, where they facilitate environmental adaptation by allowing rapid trans-cellular movement of water (classical aquaporins) or water and solutes such as glycerol (aquaglyceroporins). Here, we identified and characterized 2 aquaporin (AQP) homologs in An. sinensis: AsAQP2 (An. sinensis aquaglyceroporin) and AsAQP4 (An. sinensis aquaporin). When expressed in frog (Xenopus laevis) oocytes, AsAQP2 transported water, glycerol, and urea; AsAQP4 transported only water. Water permeation through AsAQP2 and AsAQP4 was inhibited by mercuric chloride. AsAQP2 expression was slightly higher in adult female mosquitoes than in males, and AsAQP4 expression was significantly higher in adult males. The 2 AsAQPs were highly expressed in Malpighian tubules and midgut. AsAQP2 and AsAQP4 expression was up-regulated by blood feeding compared with sugar feeding. At freezing point (0 °C), the AsAQP4 expression level increased and An. sinensis survival time reduced compared with those at normal temperature (26 °C). At low temperature (8 °C), the AsAQP2 and AsAQP4 expression levels decreased and survival time was significantly longer compared with those at 26 °C. These results suggest that AsAQP2 and AsAQP4 have roles in water homeostasis during blood digestion and in low temperature adaptation of A. sinensis. Together, our results show that the 2 AQPs are important for mosquito diuresis after blood feeding and when exposed to low temperatures.

Tomatidine ameliorates high-fat-diet/streptozocin (HFD/STZ)-induced type 2 diabetes mellitus in mice.

OBJECTIVE: To investigate the effects of tomatidine (Td) on the progression of type 2 diabetes mellitus (T2DM) in mice and uncover the mechanism. METHODS: T2DM mice model was induced by high-fat diet (HFD) and intrabitoneal injection of streptozotocin (STZ). The mice were grouped as follows: 1, control; 2, T2D; 3, T2D + tomatidine (5 mg/kg); 4, T2D + tomatidine (10 mg/kg); 5, T2D + tomatidine (20 mg/kg). Fasting blood glucose was detected by glucose metre and fasting insulin was detected by the kit to determine the effect of Td on T2DM mice. ELISA, qPCR, and Immunoblot assays were performed to detect the effects of Td on the hepatic glucose homeostasis and inflammation of mice. Immunoblot assays further confirmed the mechanism. RESULTS: Td improved blood glucose and insulin resistance in T2DM mice. In addition, Td improved liver function and lipid metabolism disorder in T2DM mice. Td also affected the liver glucose homeostasis related genes in T2DM mice. Td alleviated serum inflammation in T2DM mice. We further found that Td activated AMPK pathway, therefore ameliorating T2DM. CONCLUSION: Td ameliorated HFD/STZ-induced T2DM in mice, suggesting that it could serve as a drug of T2DM.

LINC01311 exerts an inhibitory effect in thyroid cancer progression by targeting the miR-146b-5p/IMPA2 axis.

BACKGROUND: A growing body of research suggests that long non-coding RNA (lncRNA) play an important role during the tumorigenesis and progression of cancers, including thyroid cancer (TC). Herein, we intended to uncover the role and mechanisms of LINC01311 in TC. METHODS: The relative LINC01311, miR-146b-5p, and IMPA2 expressions were quantified by subjecting TC cells and tissues to western blotting and RT-qPCR. CCK-8 and scratch-wound healing assays were carried out for the evaluation of the proliferation and migration of TC cells. The apoptosis was evaluated by flow cytometry assay and western blotting of Bax and Bcl-2 proteins. Xenograft tumor model was also used to study how LINC01311 functions during TC cell growth. Luciferase reporter and RNA immunoprecipitation (RIP) assays were performed to ascertain miR-146b-5p's interactions with LINC01311 and IMPA2 3'UTR. RESULTS: The TC cells and tissues exhibited a downregulation of LINC01311 and IMPA2 and an upregulation of miR-146b-5p. LINC01311 overexpression retarded TC cell growth in vitro as well as in vivo. The luciferase reporter and RIP assays verified that miR-146b-5p recognizes LINC01311 and IMPA2 3'UTR by base pairing. LINC01311 overexpression could counteract the oncogenic effect of miR-146b-5p in vitro. Moreover, IMPA2 upregulation could offset the tumor-promoting effect of miR-146b-5p. CONCLUSION: LINC01311-mediated inhibition of TC cell growth was achieved by targeting the miR-146b-5p/IMPA2 axis. These findings support that targeting the LINC01311/miR-146b-5p/IMPA2 axis may be a promising approach against TC progression.

Exenatide Twice Daily Plus Glargine Versus Aspart 70/30 Twice Daily in Patients With Type 2 Diabetes With Inadequate Glycemic Control on Premixed Human Insulin and Metformin.

OBJECTIVE: Many patients with type 2 diabetes treated with premixed insulin gradually have inadequate glycemic control and switch to a basal-bolus regimen, which raises some concerns for weight gain and increased hypoglycemic risk. Switching to combination use of glp-1 agonist and basal insulin may be an alternative option. METHODS: After a 12-week premixed human insulin 70/30 dosage optimization period, 200 patients with HbA1c of 7.0% to 10.0% were randomized into 24-week treatment groups with exenatide twice a day plus glargine or with aspart 70/30 twice a day. RESULTS: After 24 weeks, the patients receiving exenatide plus glargine (n = 90) had improved HbA1c control compared with those receiving aspart 70/30 (n = 90) (least squares mean change: ‒0.59 vs ‒0.13%; difference [95% CI]: ‒0.45 [‒0.74 to ‒0.17]) in the full analysis set population. Weight decreased 3.5 kg with exenatide and decreased 0.4 kg with aspart 70/30 (P < .001). The insulin dose was reduced 10.7 units/day (95% CI, ‒12.2 to ‒9.2 units; P < .001) with exenatide, and increased 9.7 units/day (95% CI, 8.2 to 11.2 units; P < .001) with aspart 70/30. The most common adverse events were gastrointestinal adverse effects in the exenatide group (nausea [21%], vomiting [16%], diarrhea [13%]). The incidence of hypoglycemia was similar in 2 groups (27% for exenatide and 38% for aspart 70/30; P = .1). CONCLUSION: In premixed human insulin‒treated patients with type 2 diabetes with inadequate glycemic control, switching to exenatide twice a day plus glargine was superior to aspart 70/30 twice a day for glycemic and weight control.