Activation of AMPK ameliorates acute severe pancreatitis by suppressing pancreatic acinar cell necroptosis in obese mice models.

Obese people with acute pancreatitis (AP) have an increased risk of developing severe acute pancreatitis (SAP), which prolongs the length of hospital stay and increases mortality. Thus, elucidation of the mechanisms through which SAP occurs in obese individuals will provide clues for possible treatment targets. Differences in early events in obese or lean patients with AP have not been conclusively reported. We selected C57BL/6 mice as lean mice models, ob/ob mice or diet induced obese (DIO) mice as obese mice models and then induced experimental AP in mice via injections of caerulein. There were suppressed p-AMPK expressions in the pancreas of obese mice, compared with same-age lean C57BL/6 mice, which were further reduced in AP mice models. Obese AP mice were treated using AICAR, a direct AMPK agonist, which prevented pancreatic damage and cell death, suppressed pancreatic enzyme levels in serum, reduced the areas of fat saponification in the peritoneal cavity, prevented injury in other organs and decreased mice mortality rate. Further assays showed that AICAR activates p-AMPK to stabilize pro-caspase-8. Pro-caspase-8 enhances RIPK3 degradation, inhibits pancreatic acinar cell necroptosis, and downregulates the release of pancreatic enzymes. Thus, activation of AMPK by AICAR alleviates pancreatic acinar cell necroptosis and converts SAP to mild acute pancreatitis in obese mice.

A duct-to-mucosa pancreaticojejunostomy for small main pancreatic duct and soft pancreas in minimally invasive pancreaticoduodenectomy.

BACKGROUND: Postoperative pancreatic fistula (POPF) is often associated with significant morbidity and mortality after the Whipple operation. Patient-related factors associated with POPF include soft pancreatic texture and a small main pancreatic duct (MPD). The traditional duct-to-mucosa anastomosis was modified to be easily performed. The aim of the study was to evaluate the simplified pancreaticojejunostomy (PJ) method in the prevention of POPF after minimally invasive pancreaticoduodenectomy (PD). METHODS: Ninety-eight patients who underwent laparoscopic pancreaticoduodenectomy (LPD) and robotic pancreaticoduodenectomy (RPD) with a simplified PJ procedure containing only two duct-to-mucosa sutures and four penetrating-sutures to anastomose the pancreatic parenchyma and jejunal seromuscular layer in our center were retrospectively studied. Demographics and clinical short-term safety were assessed. RESULTS: All LPD and RPD procedures were successfully performed. The median time of PJ was 17 min, and the median blood loss was 60 mL, with only one patient requiring transfusion. Four patients (4.1%) suffered from clinically relevant POPF (CR-POPF), including four grade B cases and no grade C cases. For patients with an MPD diameter of 3 mm or less, POPF was noted in two (4%) of the fifty patients, with all cases being grade B. Of the patients with a soft pancreas, only two (4.5%) patients suffered from grade B POPF. One patient (1.0%) experienced a 90-day mortality. Neither the main pancreatic diameter nor pancreatic texture had an impact on postoperative outcomes. CONCLUSIONS: Our technique is a simple, safe and efficient alternative to prevent POPF after LPD and RPD. This method is suitable for almost all pancreatic conditions, including cases with a small main pancreatic duct and soft pancreas, and has the potential to become the preferred procedure in low-volume pancreatic surgery centers. Our modified duct-to-mucosa PJ, which contains only two duct-to-mucosa sutures and four penetrating-sutures to anastomose the pancreatic parenchyma and jejunal seromuscular layer, is ideal for small MPD and soft pancreas when performing minimally invasive PD and has a low rate of POPF. PJ pancreaticojejunostomy, MPD main pancreatic diameter, PD pancreaticoduodenectomy, POPF postoperative pancreatic fistula.

Meiotic nuclear divisions 1 promotes proliferation and metastasis in hepatocellular carcinoma and is a potential diagnostic and therapeutic target gene.

Hepatocellular carcinoma is the cancer with the highest incidence among liver cancers and how to treat this cancer effectively is still a difficult problem we must face. We selected meiotic nuclear divisions 1 (MND1) as the study object by combining data from The Cancer Genome Atlas (TCGA) database with prognostic survival analysis. We validated the value of MND1 in evaluating the prognosis of hepatocellular carcinoma through a diagnostic and prognostic model. At the same time, cellular experiments were used to demonstrate the effect of MND1 on hepatocellular carcinoma proliferation and migration. We used short hairpin RNA (shRNA) to knock down MND1 in Hun7 and HCCLM3 cell lines. Through 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and colony formation assays, we found that knocking down MND1 reduced the proliferation of cells. Through wound healing and Transwell assays, we found that knocking down MND1 reduced cell migration and invasion. Moreover, we found that MND1 can promote the proliferation, migration, and invasion of Hep3B cells by overexpressing MND1. Therefore, in general, MND1 is expected to be a gene that can effectively diagnose and treat hepatocellular carcinoma.

Pyroptosis-related genes regulate proliferation and invasion of pancreatic cancer and serve as the prognostic signature for modeling patient survival.

OBJECTIVE: Pancreatic ductal adenocarcinoma (PDAC) has high mortality and poor prognosis. Pyroptosis can influence the prognosis of patients by regulating the proliferation, invasion, and metastasis of cancer cells. However, the role of pyroptosis-related genes (PRGs) in PDAC remains unclear. METHODS: In this study, based on the Cancer Genome Atlas (TCGA) cohort of PDAC samples, univariate Cox analysis and LASSO regression analysis were used to screen the prognostic PRGs and establish the gene signature. To further evaluate the functional significance of CASP4 and NLRP1 in PDAC, we also conducted an in vitro study to explore the mechanism of CASP4 and NLRP1 regulating the occurrence and development of PDAC. Finally, we investigated the relationship between CASP4 and NLRP1 expression levels and drug sensitivity in pancreatic cancer cells. RESULTS: A risk prediction model based on CASP4 and NLRP1 was established, which can distinguish high-risk patients from low-risk patients (P < 0.001). Both internal validation and external GEO data sets validation demonstrate good predictive capability of the model (AUC = 0.732, AUC = 0.802, AUC = 0.632, P < 0.05). In vitro, CCK8 and Transwell assay suggested that CASP4 may accelerate the progression of PDAC by promoting proliferation and migration of pancreatic cancer cells, while NLRP1 has been found to have tumor suppressive effect. It should be noted that knockdown of CASP4 reduced the level of coke death, the expression levels of acetyl-CoA carboxylase, FASN, SREBP-1 and SREBP-2 were decreased, and the number of lipid droplets was also significantly reduced. Moreover, the enrichment of signaling pathways showed that NLRP1 was significantly correlated with MAPK and RAS/ERK signaling pathways, and knocking down NLRP1 could indeed up-regulate p-ERK expression. Finally, high expression of CASP4 and low expression of NLRP1 increased the sensitivity of pancreatic cancer cells to ERK inhibitors. CONCLUSIONS: In especial, CASP4 can promote tumor progression by promoting the synthesis and accumulation of fatty acids, while NLRP1 acts on RAS/ERK signaling pathway. Both of genes play an important role in the diagnosis and treatment of PDAC, which may also affect the inhibitors of MAPK/ERK efficiency.

The complete chloroplast genome of Salsola abrotanoides (Chenopodiaceae), a desert halophyte shrub in China.

Salsola abrotanoides, one of the dominant plant species of desert vegetation, adapts well to the arid, saline, and alkaline environment in the Qinghai-Tibetan Plateau. Here, we reported the complete chloroplast sequence and characters of S. abrotanoides based on the Illumina NovaSeq Platform. The chloroplast genome is 151,622 bp in length, containing a pair of inverted repeated (IR) regions of 23,701 bp, a large single copy (LSC) region of 84,658 bp, and a small single copy (SSC) region of 19,562 bp. And the chloroplast genome sequence encodes 130 genes totally, including 85 mRNA genes, 37 tRNA genes, and 8 rRNA genes. S. abrotanoides is the first species of Genus Salsola and the chloroplast sequence will provide a valuable resource for the phylogenetic studies of Chenopodiaceae.

The gut microbiota is associated with clinical response to statin treatment in patients with coronary artery disease.

BACKGROUND: The structure and composition of the gut microbiota influence patients' response to therapeutic interventions. It is also known that the response to statin treatment can vary greatly from one patient to another, suggesting a possible connection between microbiome composition and response to statins. In the present study, we aim to explore the influence of the microbiome composition on the response to statin treatment among patients with coronary artery disease (CAD). METHODS: A prospective cohort of 836 CAD patients enrolled from January 2016 to December 2017 was used to perform a nested case-control study. We divided 110 CAD patients into two groups according to their response to statins (good response group and poor response group) and compared their gut microbiota. RESULTS: Our analysis reveals no significant difference in microbiome between the two groups. However, significant differences were found in the relative proportion of numerous genera between GR and PR groups. Most remarkably, we could observe that a poor response to statin treatment correlates to a significant decrease in the abundance of beneficial bacteria for the lipid metabolism (Akkermansia muciniphila (A. muciniphila) and Lactobacillus) and a significant increase in the abundance of bacteria (Holdemanella and Facecallibacterium). CONCLUSIONS: Gut microbiota structure is associated with the response to statin. Our results suggest that manipulation of the gut microbiota composition can be an interesting and effective treatment strategy to blood lipid control among CAD patients.

Method comparison for analyzing wound healing rates.

Wound healing scratch assay is a frequently used method to characterize cell migration, which is an important biological process in the course of development, tissue repair, and immune response for example. The measurement of wound healing rate, however, varies among different studies. Here we summarized these measurements into three types: (I) direct rate average; (II) regression rate average; and (III) average distance regression rate. Using Chinese hamster ovary (CHO) cells as a model, we compared the three types of analyses on quantifying the wound closing rate, and discovered that type I & III measurements are more resistant to outliers, and type II analysis is more sensitive to outliers. We hope this study can help researchers to better use this simple yet effective assay.

Rapamycin induces autophagy and exacerbates metabolism associated complications in a mouse model of type 1 diabetes.

Type 1 diabetes mellitus (T1DM) is characterized by lack of insulin production as a consequence of massive beta cells destruction. The contributions of autophagy to loss of beta cell mass were not clearly elucidated. Rapamycin is a specific and potent inhibitor of mammalian target of rapamycin (mTOR) and is used as the central immunosuppressant in T1DM patients especially for those who received islet transplantation. In the present study, effects of rapamycin on autophagy of T1DM were investigated in a mouse model treated with multiple low doses of streptozotocin. Rapamycin treatment led to hyperglycemia, weight loss, increased intake of food and drinking water, and islet inflammation in T1DM mice. Pathological changes including autophagy and apoptosis in pancreas, kidney, spleen and thymus, accompanied with an accumulation of LC3-II, Beclin1 and Caspase-3 protein were observed. The results indicate that rapamycin may exacerbate metabolism associated complications by activating autophagy and apoptosis in T1DM.