Inflammatory cytokines is a key point in the development of pathogenesis of SAP. Inflammatory mediators TNF-α and IL-6 are up-regulated in serum of patients with SAP and become good discriminators of SAP severity. In this study, we investigated the treatment effectiveness of Baicalein on SAP rat model. Baicalein was intravenously injected immediately after SAP induction in rats. The mortality, histopathology score, ascites fluid volume, and pro-inflammatory cytokine production were evaluated at 12 h after SAP induction. Baicalein decreased the pancreatic histopathology score, reduced ascites fluid production, protected against pancreatic injury, and improved survival in rats with SAP. The serum IL-6 and TNF-α concentrations were also down-regulated by Baicalein. Baicalein demonstrated a well curative capability on rats with SAP. The mechanism may be alleviateing pancreatic injury and inhibiting pro-inflammatory cytokines expression.

Background: Primary liver cancer (PLC) is a major cause of cancer mortality worldwide, particularly among middle-aged and elderly populations. Given increasing life expectancy, understanding PLC burden in these groups is essential. Methods: We obtained data about incidence, deaths, and disability-adjusted-life-years (DALYs) from 2000 to 2021 for PLC aged 55+ from Global Burden of Disease (GBD) 2021. Trends across sociodemographic index (SDI), etiology, age, and sex level were evaluated using age-standardized rates, estimated annual percentage change (EAPC), and percentage change. Bayesian-age-period-cohort (BAPC) model was applied to predict the global burden to 2050. Results: Globally, the cases of PLC burden among middle-aged and elderly populations increased by 74% in incidence, 67% in deaths, and 59% in DALYs. Despite rising case counts, EAPC for incidence, deaths, and DALYs declined with −0.13, −0.32, and −0.55. Trends varied by region and SDI level, with reductions in HBV- and HCV-related PLC but increases in non-alcoholic steatohepatitis (NASH) and alcohol use related PLC, particularly in high-SDI regions. Burden was the highest and increasing among those aged 75+, especially for NASH-related PLC. Globally, the male-to-female burden ratio was 2.19, though gender differences varied regionally. Finally, projection indicated that the incidence case will persistently rise from 2021 to 2050, while incidence rate will decrease first and then increase. Conclusions: Our study analyzed the global epidemiology of PLC among middle-aged and elderly populations from etiology, age and gender, and conducted a prediction outlook for the next 30 years. These findings contribute to the development of efficient and targeted health strategies to mitigate PLC burden.

Obstruction of bile ducts due to gallstones can lead to biliary acute pancreatitis (BAP). According to Perides et al., G protein-coupled bile acid receptor-1 (GPBAR1) mediates BAP. However, Zi's findings suggest that GPR39, rather than GPBAR1, mediates TLCAS-induced increases in cytosolic calcium and acinar cell necrosis, casting doubt on the role of GPBAR1 in BAP. Numerous G protein-coupled receptors on pancreatic acinar cells utilize Ca²⁺ and cyclic adenosine monophosphate (cAMP) as second messengers to manage pancreatic exocrine secretion, with significant cross-talk between these signals. The primary bile acid cholic acid (CA) and its conjugated forms are predominant in the human gallbladder. This study aimed to clarify the role and physiological significance of GPBAR1 by investigating the physiological and pathological effects of CA activation on GPBAR1 in pancreatic acinar cells. Isolated rat pancreatic acinar cells were treated with CA and CCK in vitro to observe the effect of CA-induced cAMP signaling on CCK-induced physiological and pathological calcium signaling. In vivo evaluations involved reverse biliopancreatic duct injections of 5 % sodium taurocholate (STC) or 5 % CA in rats. CA induced intracellular cAMP signaling in a concentration-dependent manner without increasing the intracellular Ca²⁺ concentration. CA did not independently cause calcium overload or enzyme activation, nor did it exacerbate calcium overload or enzyme activation from high-dose CCK. Reverse biliopancreatic duct injections of 5 % CA did not cause acute pancreatitis in the rats. Transcriptomic analysis revealed that 50 μM CA induced changes in gene expression related to protein synthesis in the endoplasmic reticulum and ribosomes. Furthermore, 50 μM CA accelerated the calcium waves and increased the enzyme secretion induced by CCK. GPBAR1 was found on the basolateral membrane in rat pancreatic tissue rather than near the apical region of acinar cells. GPBAR1 activation is not crucial for BAP activity but may play a role in bile acid regulation of pancreatic exocrine secretion, suggesting that GPBAR1 is a potential therapeutic target for pancreatic exocrine insufficiency.

Background and Objectives: Most published research has only investigated a single timepoint after the onset of severe acute pancreatitis (SAP), meaning that they have been unable to observe the relationship between the dynamic changes in cytokines and SAP progression. In this study, we attempted to reveal the relationship between dynamic changes in cytokine expression levels and SAP disease progression and the relationship between cytokines, using continuous large-scale cytokine detection. Materials and Methods: Seventy rats were randomly assigned to control (Con), sham operation (SO) and SAP groups. The SAP group was randomly allocated to five subgroups at 3, 6, 9, 12 and 15 h after the operation. In the SAP group, 5% sodium taurocholate was injected retrograde into the pancreatic bile duct. Animals in the SO group received a similar incision, a turning over of the pancreas. Control animals did not receive any treatment. We observed the survival, ascites fluid amount, pancreatic histopathological scores and serum amylase activity of SAP rats. We used the cytokine microarray to simultaneously detect 90 cytokines and the dynamic changes in one experiment and to analyze the correlation between cytokine expression and disease progression. Results: The mortality of SAP rats increased with an increase in time. Serum amylase activity, pancreatic histopathological scores and ascites fluid amount were time-dependent. Compared with normal rats, 69 cytokines in SAP rats were significantly changed for at least one timepoint, and 49 cytokines were significantly changed at different timepoints after SAP induction. The changes in inflammatory cytokines were significantly upregulated at 6 and 9 h and 12 h and then significantly decreased. Conclusions: The trend of cytokine expression in SAP rats was not consistent with the disease progression. The cytokine–cytokine receptor interaction and MAPK signal’s dominant cytokines were always highly expressed at various time points over the course of SAP.