Systemic lupus erythematosus (SLE) is a multifaceted autoimmune disorder characterized by dysregulated immune responses and autoantibody production, which affects multiple organs and varies in clinical presentation and disease severity. The development of SLE is intricate, encompassing dysregulation within the immune system, a collapse of immunological tolerance, genetic susceptibilities to the disease, and a variety of environmental factors that can act as triggers. This review provides a comprehensive discussion of the pathogenesis and treatment strategies of SLE and focuses on the progress and status of traditional and emerging treatment strategies for SLE. Traditional treatment strategies for SLE have mainly employed non-specific approaches, including cytotoxic and immunosuppressive drugs, antimalarials, glucocorticoids, and NSAIDs. These strategies are effective in mitigating the effects of the disease, but they are not a complete cure and are often accompanied by adverse reactions. Emerging targeted therapeutic drugs, on the other hand, aim to control and treat SLE by targeting B and T cells, inhibiting their activation and function, as well as the abnormal activation of the immune system. A deeper understanding of the pathogenesis of SLE and the exploration of new targeted treatment strategies are essential to advance the treatment of this complex autoimmune disease.

Nonalcoholic fatty liver disease (NAFLD) has emerged as a common public health problem that can progress to end-stage liver disease. A high-fat diet (HFD) may promote the development of NAFLD through a mechanism that is poorly understood. We adopted a proteomic approach to examine the effect of HFD on the liver proteome during the progression of NAFLD. Male Sprague-Dawley rats fed an HFD for 4, 12, and 24 weeks replicated the progression of human NAFLD: steatosis, nonspecific inflammation, and steatohepatitis. Using two-dimensional difference gel electrophoresis (DIGE) combined with matrix-assisted laser desorption ionization time of flight/time of flight analysis, 95 proteins exhibiting significant changes (ratio ≥ 1.5 or ≤−1.5, P < 0.05) during the development of NAFLD were identified. Biological functions for these proteins reflected phase-specific characteristics during the progression of the disease. The potential role of enoyl–coenzyme A hydratase (ECHS1), an enzyme that catalyzes the second step of mitochondrial fatty acid beta-oxidation, received further investigation. First, the reduced protein level of ECHS1 was validated both in rat models and in patients with biopsy-proven hepatic simple steatosis via immunoblotting or immunohistochemical analysis. Then the small interfering RNA (siRNA)–mediated knockdown of ECHS1 in the murine hepatocyte cell line alpha mouse liver 12 (AML12) demonstrated increased cellular lipid accumulation induced by free fatty acid (FFA) overload. Furthermore, using a hydradynamic transfection method, the in vivo silencing effect of siRNA duplexes targeting ECHS1 was further investigated in mice. Administering ECHS1 siRNA specifically reduced the expression of ECHS1 protein in mice liver, which significantly exacerbated the hepatic steatosis induced by an HFD. Conclusion: Our results revealed that ECHS1 down-regulation contributed to HFD-induced hepatic steatosis, which may help clarify the pathogenesis of NAFLD and point to potential targets for therapeutic interventions. (HEPATOLOGY 2010.)

Purpose: Pseudomonas aeruginosa is recognized as a major cause of severe and potentially life-threatening infection. However, P. aeruginosa isolates with the phenotype of being carbapenem resistant and cephalosporin susceptible (Carb-R/Ceph-S) have not been thoroughly characterized to date. The aim of this study was to assess the mechanisms, risk factors, and clinical impact of Carb-R/Ceph-S P. aeruginosa bacteremia on mortality. Patients and methods: We conducted a retrospective case–case–control study of the risk factors and clinical outcomes of hospitalized patients with Carb-R/Ceph-S P. aeruginosa bacteremia from 2011 to 2017 in Chongqing, China. Case patients infected with Carb-R/Ceph-S P. aeruginosa, carbapenem-susceptible and cephalosporin-susceptible (Carb-S/Ceph-S) P. aeruginosa, and controls with no P. aeruginosa bacteremia were compared at a ratio of 1:1:2. Real-time reverse transcription polymerase chain reaction was performed to assess resistance mechanisms. A multivariate logistic regression model was performed to investigate several potential predictors for mortality. Results: We collected 63 Carb-R/Ceph-S P. aeruginosa isolates during the study period. None of these isolates possessed carbapenemase or extended-spectrum β-lactamase-encoding genes. The overall 30-day mortality rate was 27.0%. Real-time reverse transcription polymerase chain reaction analysis showed that an overexpression of efflux systems and decreased expression of OprD were associated with Carb-R/Ceph-S P. aeruginosa. Multivariate analysis indicated that 30-day readmission, central venous catheters, and exposure to carbapenems were unique independent predictors for acquiring Carb-R/Ceph-S P. aeruginosa bacteremia. Additionally, hematologic malignancy was a peculiar predictor for Carb-S/Ceph-S P. aeruginosa bacteremia. Notably, total parenteral nutrition was the only common factor of both Carb-R/Ceph-S and Carb-S/Ceph-S groups compared to controls. In a multivariate analysis for the outcome, intensive care unit admission and septic shock were identified as the independent predictors for mortality. Conclusion: Our findings can potentially improve the ability of physicians to identify the high-risk patients, and carbapenems were noted to potentially increase the risk of Carb-R/Ceph-S P. aeruginosa. Additionally, cephalosporin should be considered a valuable therapeutic option for such cases of bacteremia.

In fetal hematopoietic organs, the switch from hematopoiesis is hypothesized to be a critical time point for organogenesis, but it is not yet evidenced. The transient coexistence of hematopoiesis will be useful to understand the development of fetal liver (FL) around this time and its relationship to hematopoiesis. Here, the temporal and the comparative transcriptomic and proteomic profiles were observed during the critical time points corresponding to the initiation (E11.5), peak (E14.5), recession (E15.5), and disappearance (3 ddp) of mouse FL hematopoiesis. We found that E11.5-E14.5 corresponds to a FL hematopoietic expansion phase with distinct molecular features, including the expression of new transcription factors, many of which are novel KRAB (Kruppel-associated box)-containing zinc finger proteins. This time period is also characterized by extensive depression of some liver functions, especially catabolism/utilization, immune and defense, classical complement cascades, and intrinsic blood coagulation. Instead, the other liver functions increased, such as xenobiotic and sterol metabolism, synthesis of carbohydrate and glycan, the alternate and lectin complement cascades and extrinsic blood coagulation, and etc. Strikingly, all of the liver functions were significantly increased at E14.5-E15.5 and thereafter, and the depression of the key pathways attributes to build the hematopoietic microenvironment. These findings signal hematopoiesis emigration is the key to open the door of liver maturation.

Background: Activation of hepatic stellate cells (HSCs) is essential for the pathogenesis of liver fibrosis, there is no effective drug used to prevent or reverse the fibrotic process.Methods: With human hepatic stellate cell line LX-2 and mouse model of CCl₄-induced liver fibrosis, we investigated the anti-fibrotic effect to liver fibrosis of extracellular vesicles (EVs) extracted from tea leaves through cytological tests such as cell proliferation, cell migration, and cell fibrotic marker.Results: It was found that tea-derived EVs (TEVs) inhibited HSCs activation. In CCl₄-induced liver fibrosis model, TEVs treatment can significantly improve the pathological changes of liver tissue, inhibit collagen deposition, reduce the number of lipid droplets in liver tissue, and reduce serum AST and ALT levels. In addition, TEVs inhibited TGF-β1 signaling and miR-44 in TEVs had the potential inhibitory effect on liver fibrosis.Conclusions: Taken together, our work suggesting that TEVs are novel therapeutic potential for liver fibrosis.