Enhancing organoid culture: harnessing the potential of decellularized extracellular matrix hydrogels for mimicking microenvironments.

Over the past decade, organoids have emerged as a prevalent and promising research tool, mirroring the physiological architecture of the human body. However, as the field advances, the traditional use of animal or tumor-derived extracellular matrix (ECM) as scaffolds has become increasingly inadequate. This shift has led to a focus on developing synthetic scaffolds, particularly hydrogels, that more accurately mimic three-dimensional (3D) tissue structures and dynamics in vitro. The ECM-cell interaction is crucial for organoid growth, necessitating hydrogels that meet organoid-specific requirements through modifiable physical and compositional properties. Advanced composite hydrogels have been engineered to more effectively replicate in vivo conditions, offering a more accurate representation of human organs compared to traditional matrices. This review explores the evolution and current uses of decellularized ECM scaffolds, emphasizing the application of decellularized ECM hydrogels in organoid culture. It also explores the fabrication of composite hydrogels and the prospects for their future use in organoid systems.

Beneficial effects of Wuzhi Capsule on tacrolimus blood concentrations in liver transplant patients with different donor-recipient CYP3A5 genotypes.

WHAT IS KNOWN AND OBJECTIVE: Tacrolimus (Tac) is an immunosuppressant that is widely used to prevent allograft rejection in patients after liver transplantation. Its metabolism mainly depends on the cytochrome P450 3A5 (CYP3A5), which has genetic polymorphisms. Recently, a Chinese herbal medicine known as Wuzhi Capsule (WZC) was shown to increase Tac blood concentrations by inhibiting the activity of CYP3A in animal studies in rats. To date, it remains unexplored whether WZC can be efficiently used to enhance the blood concentration of Tac in liver transplant patients with different donor-recipient CYP3A5 genotypes. METHODS: A total of 185 liver transplant patients were enrolled and two-way ANOVA was carried out, then they were divided into four groups according to the combinations of donor-recipient CYP3A5 phenotypes. WZC was given to patients when the dose of Tac was ≥4 mg, and the dose-adjusted C0 (C0 /D) of Tac measured twice in succession was ≤1 ng/ml/mg. The blood trough concentration of Tac (C0 ), C0 /D, and dose- and body weight-adjusted C0 (C0 /D/W) was analysed on days 7 and 14 after liver transplantation. RESULTS: The genotypes of donor and recipient or WZC had significant effects on C0, C0/D and C0/D/W. There were significant differences in the Tac blood concentrations between the groups. The recipient expression (*1)/donor expression (*1) (R+/D+) group had the lowest C0 , C0 /D and C0 /D/W among the four groups. Furthermore, a larger proportion of patients in the CYP3A5 expression groups required Tac dose adjustment to achieve a therapeutic effect and were given Tac with WZC. Notably, the use of WZC significantly increased the blood concentrations of Tac in the CYP3A5 expression groups and greater increases in the C0 /D and C0 /D/W were significantly associated with higher doses of WZC in the CYP3A5 expression groups. What is more, WZC reduced the hospitalization cost of patients to a certain extent. WHAT IS NEW AND CONCLUSION: WZC significantly increased the C0 , C0 /D and C0 /D/W in the CYP3A5 expression groups and reduced the hospitalization expenses of patients to a certain extent. What is more, greater increases in the C0 /D and C0 /D/W were significantly associated with higher doses of WZC.

Lipid droplet deposition in the regenerating liver: A promoter, inhibitor, or bystander?

Liver regeneration (LR) is a complex process involving intricate networks of cellular connections, cytokines, and growth factors. During the early stages of LR, hepatocytes accumulate lipids, primarily triacylglycerol, and cholesterol esters, in the lipid droplets. Although it is widely accepted that this phenomenon contributes to LR, the impact of lipid droplet deposition on LR remains a matter of debate. Some studies have suggested that lipid droplet deposition has no effect or may even be detrimental to LR. This review article focuses on transient regeneration-associated steatosis and its relationship with the liver regenerative response.

Unveiling the power of microenvironment in liver regeneration: an in-depth overview.

The liver serves as a vital regulatory hub for various physiological processes, including sugar, protein, and fat metabolism, coagulation regulation, immune system maintenance, hormone inactivation, urea metabolism, and water-electrolyte acid-base balance control. These functions rely on coordinated communication among different liver cell types, particularly within the liver's fundamental hepatic lobular structure. In the early stages of liver development, diverse liver cells differentiate from stem cells in a carefully orchestrated manner. Despite its susceptibility to damage, the liver possesses a remarkable regenerative capacity, with the hepatic lobule serving as a secure environment for cell division and proliferation during liver regeneration. This regenerative process depends on a complex microenvironment, involving liver resident cells, circulating cells, secreted cytokines, extracellular matrix, and biological forces. While hepatocytes proliferate under varying injury conditions, their sources may vary. It is well-established that hepatocytes with regenerative potential are distributed throughout the hepatic lobules. However, a comprehensive spatiotemporal model of liver regeneration remains elusive, despite recent advancements in genomics, lineage tracing, and microscopic imaging. This review summarizes the spatial distribution of cell gene expression within the regenerative microenvironment and its impact on liver regeneration patterns. It offers valuable insights into understanding the complex process of liver regeneration.

Hem-o-lok clip found in the common bile duct 3 years after laparoscopic cholecystectomy and surgical exploration.

Endoscopic retrograde cholangiopancreatography (ERCP) with stone extraction is a common and preferred choice for gallstone disease. Laparoscopic common bile duct exploration (LCBDE) and laparoscopic cholecystectomy (LC) are being increasingly used for managing choledocholithiasis and cholecystolithiasis. We report a case of a Hem-o-lok clip that was dropped into the common bile duct (CBD) after LC and surgical common bile duct exploration (CBDE). An 84-year-old man presented with right upper quadrant pain and jaundice for 2 months, and chills and hyperpyrexia for 1 day. The patient had received ERCP and surgical CBDE at a local hospital 3 years previously. The patient first received ERCP and endoscopic nasobiliary drainage (ENBD). When laboratory tests were normal, the patient then received LCBDE. During exploration, stones and a Hem-o-lok clip in the CBD were removed. The patient made good progress after LCBDE + T-tube placement and was discharged from hospital. The findings from this case suggest the following: 1) an appropriate therapy method should be considered for certain gallstone diseases, especially for choledocholithiasis and cholecystolithiasis; and 2) a Hem-o-lok clip should be carefully used during laparoscopic or robot-assisted surgery and the Hem-o-lok clip should not be in close proximity to the incision on the CBD.

Pretreatment albumin to globulin ratio can serve as a prognostic marker in human cancers: a meta-analysis.

PURPOSE: Our meta-analysis aims to investigate the prognostic role of pretreatment albumin to globulin ratio (AGR) in human cancers. METHODS: Available databases were searched up to Sept 25th, 2017. Pooled hazard ratios (HRs) and risk ratio (RRs) with their corresponding 95% confidence intervals (CIs) were used to assess the prognostic impact of AGR on overall survival (OS)/disease-free survival (DFS)/progression-free survival (PFS) and 5-year mortality respectively. RESULTS: Totally, 28 studies with 15 356 cancer patients were included. Our results demonstrated that low pretreatment AGR is associated with poor OS (HR=2.08, 95%CI:1.78-2.44, univariate results; HR=1.75, 95%CI:1.56-1.97, multivariate results), poor DFS (HR=1.96, 95%CI:1.48-2.59, univariate results; HR=1.64, 95%CI:1.26-2.14, multivariate results) and poor PFS (HR=1.89, 95%CI:1.61-2.22, univariate results; HR=1.66, 95%CI:1.32-2.0, multivariate results). Meanwhile, low pretreatment AGR is also associated with increased 5-year mortality (RR=2.12, 95%CI:1.48-3.03). Moreover, this significant correlation was not altered by stratified analysis according to publication times, sample sizes, patient origins, AGR cutoff values, cancer systems, treatment methods or HR sources. CONCLUSION: Low pretreatment AGR is associated with poor prognosis in human cancers, and AGR should be used as a prognostic marker during cancer therapy.