Oral oligofructose challenge reduces expression of glucose transport-1 and 5'-adenosine monophosphate-activated protein kinase in lamellar wall of Holstein heifer claw.

The laminar tissue of bovine laminitis may undergo energy failure. The expression of glucose transport protein-1 (GLUT-1) and 5'-adenosine monophosphate-activated protein kinase (AMPK) affects the energy metabolism of digital laminar tissue. This study aimed to determine the expression of glucose uptake and AMPK in laminar wall corium of Holstein heifer claw by oral administration of oligofructose. A total of twelve clinically healthy Holstein heifers were selected and divided into two groups, including control (CON, n = 6) and experimental (OF, n = 6) groups. The heifers of OF group were given 17 g/kg BW oligofructose dissolved in water (20 mL/kg BW) and the heifers of CON group were given water only (20 mL/kg BW). The laminar tissues were collected after euthanasia. The amount of protein and transcript expression of AMPK and GLUT-1 were determined by western blot and quantitative reverse transcription-polymerase chain reaction (qRT-PCR), respectively. Expressions of phosphoenolpyruvate carboxy-kinase (PEPCK), receptor-c coactivator1-α (PGC-1α) and peroxisome proliferator-activated receptor-γ (PPAR-γ) were determined by qRT-PCR. The heifers of OF group showed no significant change in the expression and concentration of AMPK. The phosphor-(Thr172) AMPK and GLUT-1 were significantly decreased, while the gene contents of PPAR-γ and PGC-1α were significantly increased. The activation of AMPK and GLUT-1 in digital laminar tissues of heifers was inhibited, which may contribute to digital laminar tissue damage.

Case report: a p.C618S RET proto-oncogene germline mutation in a large Chinese pedigree with familial medullary thyroid carcinoma.

We report a Chinese pedigree with familial medullary thyroid carcinoma. Direct sequencing of the entire coding sequences of Rearranged during Transfection (RET) identified a recurrent c.T1852A (p.C618S) mutation in 13 of 23 members. The polymorphisms c.A135G (p.A45A), c.A1296G (p.A432A), c.T2307G (p.L769L) and IVS19 + 15T > C were also found in 13 carriers, and c.G2073A (p.G691S) was found in 1 carrier. Of the 13 carriers, seven (mean age: 42.6 years, range: 27-64) presented MTC as the isolated clinical phenotype, with elevated basal serum calcitonin (average: 1077.9 ng/L, range: 504-2,652) and a mean diameter of thyroid nodules of 2.97 cm (range: 1.6-4.3); they underwent a total thyroidectomy with modified bilateral/unilateral neck dissection and/or level VI lymph node dissection. The other 6 carriers did not accept surgery (4 rejected, 2 awaited). These were 2 older patients (63 and 32 years) with elevated calcitonin (1359 and 41.4 ng/L) and multi-centric hypoechoic nodules (1.5 and 0.6 cm) with calcifications in both/left thyroid lobes; and Doppler ultrasound showed normal bilateral thyroids in 4 younger carriers (median age: 8.3 years, range: 4-12) but with increased calcitonin (average: 9.7 ng/L, range: 7.87-12.2) in 3 of them. The phenotype here is consistent with the clinical symptoms reported worldwide. We recommend that screening of hotspot regions of RET should be preferentially carried out, while whole-exon sequencing should be performed when clinical signs fail to reveal hotspot mutations or different phenotype discrepancies. Moreover, we strongly suggest prophylactic thyroidectomy should be performed before age 5 in carriers with p.C618S to prevent the occurrence and metastasis of MTC.