Blocking Wnt Secretion Reduces Growth of Hepatocellular Carcinoma Cell Lines Mostly Independent of β-Catenin Signaling

AbstractAberrant activation of Wnt/β-catenin signaling plays a key role in the onset and development of hepatocellular carcinomas (HCC), with about half of them acquiring mutations in either CTNNB1 or AXIN1. However, it remains unclear whether these mutations impose sufficient β-catenin signaling or require upstream Wnt ligand activation for sustaining optimal growth, as previously suggested for colorectal cancers. Using a panel of nine HCC cell lines, we show that siRNA-mediated knockdown of β-catenin impairs growth of all these lines. Blocking Wnt secretion, by either treatment with the IWP12 porcupine inhibitor or knockdown of WLS, reduces growth of most of the lines. Unexpectedly, interfering with Wnt secretion does not clearly affect the level of β-catenin signaling in the majority of lines, suggesting that other mechanisms underlie the growth-suppressive effect. However, IWP12 treatment did not induce autophagy or endoplasmic reticulum (ER) stress, which may have resulted from the accumulation of Wnt ligands within the ER. Similar results were observed for colorectal cancer cell lines used for comparison in various assays. These results suggest that most colorectal and liver cancers with mutations in components of the β-catenin degradation complex do not strongly rely on extracellular Wnt ligand exposure to support optimal growth. In addition, our results also suggest that blocking Wnt secretion may aid in tumor suppression through alternative routes currently unappreciated

Assessing Groundnut (Arachis hypogaea L.) Genotype Yields and Yield Traits with Different Planting Geometries on Broad Bed and Furrows

A field study on “Assessing Groundnut (Arachis hypogaea L.) genotype yields and yield traits with different planting geometries on broad bed and furrows” was conducted during rabi season of 2022 in the experimental field at International Crops Research Institute for the Semi-Arid Tropics (ICRISAT), Hyderabad, Telangana. The experiment was laid out in factorial randomised block design with three replications. Total 16 treatment combinations consisted of four planting geometries (P1) 30 × 10 cm, (P2) 15:15 × 10 cm, (P3) 20:20 × 10 cm, (P4) 25:25 × 10 cm and four varieties (V1) Girnar 4, (V2) Girnar 5, (V3) Avtar, (V4) K6. The important findings emerged from this investigation found that groundnut sown at the spacing of (P4) 25:25 × 10 cm recorded significantly higher number of pods plant-1 (33.0), kernels pod-1 (2.0), test weight (38.7 g), shelling percentage (67.1%), pod yield (1792 kg ha-1) followed by (P3) 20:20 × 10 cm, (P4) 30 × 10 cm and (P2) 15:15 × 10 cm. The genotype V2 (Girnar 5) performed best in yield and yield contributing characteristics than other genotypes and it was on par with V1 (Girnar 4). Hence, our results concluded that (P4) 25:25 × 10 cm spacing, performing best with (V2) Girnar 5 and (V1) Girnar 4 varieties

The Association of Coloproctology of Great Britain and Ireland consensus guidelines in surgery for inflammatory bowel disease.

AIM There is a requirement of an expansive and up to date review of surgical management of inflammatory bowel disease (IBD) that can dovetail with the medical guidelines produced by the British Society of Gastroenterology. METHODS Surgeons who are members of the ACPGBI with a recognised interest in IBD were invited to contribute various sections of the guidelines. They were directed to produce a procedure based document using literature searches that were systematic, comprehensible, transparent and reproducible. Levels of evidence were graded. An editorial board was convened to ensure consistency of style, presentation and quality. Each author was asked to provide a set of recommendations which were evidence based and unambiguous. These recommendations were submitted to the whole guideline group and scored. They were then refined and submitted to a second vote. Only those that achieved >80% consensus at level 5 (strongly agree) or level 4 (agree) after 2 votes were included in the guidelines. RESULTS All aspects of surgical care for IBD have been included along with 157 recommendations for management. CONCLUSION These guidelines provide an up to date and evidence based summary of the current surgical knowledge in the management of IBD and will serve as a useful practical text for clinicians performing this type of surgery