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Background: Hyperlipidaemic acute pancreatitis (HLAP) has become the most common cause of acute pancreatitis (AP) not due to gallstones or alcohol (Mosztbacher et al, Pancreatology 20:608-616, 2020; Yin et al, Pancreas 46:504-509, 2017). Therapeutic plasma exchange (TPE) has been reported to be effective in reducing serum TG levels which is important in management of HLAP (World J Clin Cases 9:5794-803, 2021). However, studies on TPE are mostly focusing on cases reports, TPE remains poorly evaluated till date and need to be compared with conservative therapy with a well-designed study. Methods: A retrospectively cohort study on HLAP patients between January 2003 and July 2023 was conducted. Factors correlated with efficacy of TPE were included in a propensity model to balance the confounding factors and minimize selection bias. Patients with and without TPE were matched 1:2 based on the propensity score to generate the compared groups. Lipid profiles were detected on admission and consecutive 7 days. The triglyceride (TG) level decline rates, percentage of patients to reach the target TG levels, early recurrence rate, local complications and mortality were compared between groups. Results: A total of 504 HLAP patients were identified. Since TPE was scarcely performed on patients with TG < 11.3 mmol/L, 152 patients with TG level 5.65 to 11.3 mmol/L were excluded while 352 with TG ≧11.3 mmol/L were enrolled. After excluding 25 cases with incomplete data or pregnancy, 327 patients, of whom 109 treated without TPE while 218 treated with TPE, were included in data analysis. One-to-two propensity-score matching generated 78 pairs, 194 patients with well-balanced baseline characteristics. Of 194 patients enrolled after matching done, 78 were treated without while 116 with TPE. In the matched cohort (n = 194), patients treated with TPE had a higher TG decline rate in 48 h than those without TPE (70.00% vs 54.00%, P = 0.001); the early recurrence rates were 8.96% vs 1.83%, p = 0.055. If only SAP patients were analyzed, the early recurrence rates were 14.81% vs 0.00% (p = 0.026) respectively. For patients with CT severity index (CTSI) rechecked within 14 days, early CTSI improment rate were 40.90% vs 31.91%. Local complications checked 6 months after discharge were 44.12% vs 38.30%. Mortality was 1.28% vs 1.72%. No differences were found in early stage CTSI improment rate (P =.589), local complications (P =.451) or motality between two groups. Conclusions: TPE reduces TG levels more quickly in 48 h compared with those with conservative treatment, but no difference in the consecutive days. TPE tends to reduce the early recurrence rate comparing with conventional therapy, but TPE has no advantages in improving CTSI in early stage, and no improvement for outcomes including local complications and mortalty. [ABSTRACT FROM AUTHOR]

Background: Studies on chemerin/chemokine-like receptor-1 have mainly focused on adipose and liver with the intestinal tissues largely overlooked. In this study conducted on obese mice, we have explored: 1) CMKLR1 expression in the ileums; 2) CMKLR1 inhibitor α-NETA on body weight and intestinal mucosa integrity hence the impact on hepatic steatosis and pathway involved. Methods: Nineteen male C57BL/6 mice were randomly divided into five groups: normal diet group (ND), high-fat diet group (HFD), HFD + α-NETA group (NETA), HFD + PD98059 group (PD) and HFD + α-NETA + PD98059 group (NETA + PD). Mice were fed either with a chow diet or HFD for 12 weeks. At 12th week, mice of ND were put on the diet as before; mice of NETA received daily treatments of α-NETA (30 mg/kg) via gavage; mice of PD received daily treatment of PD98059 via tail vein injection; mice of NETA + PD received daily treatment of α-NETA + PD98059, all for another 4 weeks. At the time intervention ended, mice were sacrificed. The body weight, the liver pathologies were assessed. Ileal CMKLR1 mRNA was evaluated by rtPCR; ZO-1, ERK1/2 protein expression of ileal tissues by western blotting; liver TNF-α and serum endotoxin by Elisa. Results: More weight gains in mice of HFD than ND (37.90 ± 3.00 g) vs (24.47 ± 0.50 g), P = 0.002; α-NETA reduced the body weight (33.22 ± 1.90 g) vs (37.90 ± 3.00 g), P = 0.033; and further reduced by NETA + PD98059: (31.20 ± 1.74 g) vs (37.30 ± 4.05 g), P = 0.032. CMKLR1 mRNA expression was up-regulated in ileum in group HFD compared with ND and down-regulated by α-NETA. Steatosis was only alleviated in group PD + NETA with less weight gain. No impact of α-NETA on ileal ZO-1 or pERK with western blotting, and no endotoxin level changes were detected. TNF-α was higher in group HFD than in group ND, while no significant difference between other groups. Conclusions: CMKLR1 mRNA was up-regulated in the ileum of obese mice and down-regulated by α-NETA along with a body weight control collaborating with ERK inhibitor PD98059. Steatosis was alleviated in a weight dependent way. α-NETA has no influence on intestinal mucosal integrity and no impact on steatohepatitis progression. [ABSTRACT FROM AUTHOR]

Three-dimensional (3D) organoid models derived from human pluripotent stem cells provide a platform for studying human development and understanding disease mechanisms. Most studies that examine biallelic inactivation of the cell cycle regulator Retinoblastoma 1 (RB1) and the link to retinoblastoma is in mice, however, less is known regarding the pathophysiological role of RB1 during human retinal development. To study the role of RB1 in early human retinal development and tumor formation, we generated retinal organoids from CRISPR/Cas9-derived RB1-null human embryonic stem cells (hESCs). We showed that RB is abundantly expressed in retinal progenitor cells in retinal organoids and loss of RB1 promotes S-phase entry. Furthermore, loss of RB1 resulted in widespread apoptosis and reduced the number of photoreceptor, ganglion, and bipolar cells. Interestingly, RB1 mutation in retinal organoids did not result in retinoblastoma formation in vitro or in the vitreous body of NOD/SCID immunodeficient mice. Together, our work identifies a crucial function for RB1 in human retinal development and suggests that RB1 deletion alone is not sufficient for tumor development, at least in human retinal organoids. A model of the role of RB1 during human retinal development. In wild-type cells, RB1 regulates entry into S-phase. While RB1 mutation in retinal organoids did not result in retinoblastoma formation, either in vitro or when injected into vitreous body of NOD/SCID mice, loss of RB1 promotes an accumulation of cells in S-phase, causes widespread apoptosis, and reduces the number of photoreceptor, ganglion and bipolar cells. Image 1 • RB expression is highest in progenitor cells and downregulated during maturation stages. • RB1 is required for S-phase entry and cell survival in retinal organoids. • RB1 is necessary for photoreceptor, ganglion and bipolar cell differentiation. • Loss of RB1 is not sufficient for retinoblastoma formation in retinal organoids. [ABSTRACT FROM AUTHOR]

Bovine embryonic stem cells (bESCs) extend the lifespan of the transient pluripotent bovine inner cell mass in vitro. After years of research, derivation of stable bESCs was only recently reported. Although successful, bESC culture relies on complex culture conditions that require a custom-made base medium and mouse embryonic fibroblasts (MEF) feeders, limiting the widespread use of bESCs. We report here simplified bESC culture conditions based on replacing custom base medium with a commercially available alternative and eliminating the need for MEF feeders by using a chemically-defined substrate. bESC lines were cultured and derived using a base medium consisting of N2B27 supplements and 1% BSA (NBFR-bESCs). Newly derived bESC lines were easy to establish, simple to propagate and stable after long-term culture. These cells expressed pluripotency markers and actively proliferated for more than 35 passages while maintaining normal karyotype and the ability to differentiate into derivatives of all three germ lineages in embryoid bodies and teratomas. In addition, NBFR-bESCs grew for multiple passages in a feeder-free culture system based on vitronectin and Activin A medium supplementation while maintaining pluripotency. Simplified conditions will facilitate the use of bESCs for gene editing applications and pluripotency and lineage commitment studies. [ABSTRACT FROM AUTHOR]