PD-1/PD-L1, PD-1/PD-L2, and other co-inhibitory signaling pathways in transplantation

[EN] Transplantation of cells, tissues and vascularized solid organs is a successful therapeutic intervention for many end-stage chronic diseases. The combination of co-stimulatory blockade with the delivery of negative signals to T cells through co-inhibitory receptors would provide a robust approach to modulating T-cell receptor signaling and improving alloantigen-specific control of transplant rejection. This approach based on fundamental knowledge of APC/T-cell interactions may complement conventional therapies in the near future to reinforce long-term allograft survival, and permit minimal immunosuppression. The focus of this review was primarily on two major co-inhibitory signaling pathways, namely PD-1/PD-L1/PD-L2 and BTLA/CD160/HVEM/LIGHT that have been thoroughly characterized in murine models of transplantation using genetically modified mice, specific monoclonal antibodies and fusion proteinsSIThis work has been supported by grants FIS 01-3026 and FIS PI-050021 of Fondo de Investigaciones Sanitarias (Ministerio de Sanidad y Consumo, Spanish Government, Spain) to JIR

Preparation of octacosanol from filter mud produced after sugarcane juice clarification

Filter mud from sugarcane juice clarification containing 6.85 g/100 g waxes was used for octacosanol extraction by supercritical CO2 and hot ethanol reflux method, respectively. Comparing with hot ethanol reflux extraction, supercritical CO2 extraction provided a similar yield of waxes but a higher content of octacosanol in the waxes (29.65 g/100 g vs. 22.52 g/100 g). However, saponification of the waxes extracted by hot ethanol reflux extraction has significantly increased octacosanol content to 47.8 g/100 g. For high efficient preparation of octacosanol from filter mud, hot ethanol reflux extraction of waxes followed by saponification was the method of choice.</p

Impaired lipid metabolism in idiopathic pulmonary alveolar proteinosis

<p>Abstract</p> <p>Background</p> <p>It is well known that lipids abnormally accumulate in the alveoli during idiopathic pulmonary alveolar proteinosis (PAP). It is unclear, however, whether lipids also abnormally accumulate in serum. This study investigated the serum lipid panels in idiopathic PAP patients and explored the relationships between serum levels and the severity of idiopathic PAP.</p> <p>Methods and Results</p> <p>Clinical data including the level of serum lipids were evaluated in 33 non-diabetic idiopathic PAP patients and 157 healthy volunteers. Serum levels of triglyceride were higher in PAP patients than in healthy subjects (median: 192.00 mg/dl (<it>P</it>₂₅: 104.36, <it>P</it>₇₅: 219.00) <it>vs </it>119.56 mg/dl (<it>P</it>₂₅: 78.81, <it>P</it>₇₅: 193.03), <it>P </it>< 0.05), while high-density lipoprotein cholesterol (HDL-C) levels were lower in patients than in the control group (42.50 ± 10.30 <it>vs </it>51.34 ± 12.06 mg/dl, <it>P </it>< 0.01). Forced expiratory volume in one second and forced vital capacity in hypertriglyceridemia patients were lower than those in patients with normal triglyceride. Serum LDL-C and HDL-C ratio correlated negatively with PaO₂(r = -0.403, <it>P </it>< 0.05) and positively with lactate dehydrogenase (r = 0.381, <it>P </it>< 0.05).</p> <p>Conclusions</p> <p>PAP associates with high triglyceride and low HDL levels in the serum, and these lipids provide potential intervention strategy for treatment.</p

Small intestinal CD103+ dendritic cells display unique functional properties that are conserved between mice and humans

A functionally distinct subset of CD103+ dendritic cells (DCs) has recently been identified in murine mesenteric lymph nodes (MLN) that induces enhanced FoxP3+ T cell differentiation, retinoic acid receptor signaling, and gut-homing receptor (CCR9 and α4β7) expression in responding T cells. We show that this function is specific to small intestinal lamina propria (SI-LP) and MLN CD103+ DCs. CD103+ SI-LP DCs appeared to derive from circulating DC precursors that continually seed the SI-LP. BrdU pulse-chase experiments suggested that most CD103+ DCs do not derive from a CD103− SI-LP DC intermediate. The majority of CD103+ MLN DCs appear to represent a tissue-derived migratory population that plays a central role in presenting orally derived soluble antigen to CD8+ and CD4+ T cells. In contrast, most CD103− MLN DCs appear to derive from blood precursors, and these cells could proliferate within the MLN and present systemic soluble antigen. Critically, CD103+ DCs with similar phenotype and functional properties were present in human MLN, and their selective ability to induce CCR9 was maintained by CD103+ MLN DCs isolated from SB Crohn's patients. Thus, small intestinal CD103+ DCs represent a potential novel target for regulating human intestinal inflammatory responses

Osthole Ameliorates Renal Fibrosis in Mice by Suppressing Fibroblast Activation and Epithelial-Mesenchymal Transition

Renal fibrosis is a common pathway of virtually all progressive kidney diseases. Osthole (OST, 7-Methoxy-8-(3-methylbut-2-enyl)-2-chromenone), a derivative of coumarin mainly found in plants of the Apiaceae family, has shown inhibitory effects on inflammation, oxidative stress, fibrosis and tumor progression. The present study investigated whether OST mediates its effect via suppressing fibroblast activation and epithelial-mesenchymal transition (EMT) in unilateral ureteral obstruction (UUO)-induced renal fibrosis in mice. Herein, we found that OST inhibited fibroblast activation in a dose-dependent manner by inhibiting the transforming growth factor-β1 (TGFβ1)-Smad pathway. OST also blocked fibroblast proliferation by reducing DNA synthesis and downregulating the expressions of proliferation- and cell cycle-related proteins including proliferating cell nuclear antigen (PCNA), CyclinD1 and p21 Waf1/Cip1. Meanwhile, in the murine model of renal interstitial fibrosis induced by UUO, myofibroblast activation with increased expression of α-smooth muscle actin (α-SMA) and proliferation were attenuated by OST treatment. Additionally, we provided in vivo evidence suggesting that OST repressed EMT with preserved E-cadherin and reduced Vimentin expression in obstructed kidney. UUO injury-induced upregulation of EMT-related transcription factors, Snail family transcriptional repressor-1(Snail 1) and Twist family basic helix-loop-helix (BHLH) transcription factor (Twist) as well as elevated G2/M arrest of tubular epithelial cell, were rescued by OST treatment. Further, OST treatment reversed aberrant expression of TGFβ1-Smad signaling pathway, increased level of proinflammatory cytokines and NF-kappaB (NF-κB) activation in kidneys with obstructive nephropathy. Taken together, these findings suggest that OST hinder renal fibrosis in UUO mouse mainly through inhibition of fibroblast activation and EMT

Comparative analysis of the phenolic contents and antioxidant activities of different parts of two pomegranate (Punica granatum L.) Cultivars: ‘Tunisia’ and ‘Qingpi’

Pomegranate (Punica granatum L.), with its abundant phenolic substances and strong antioxidant activity, holds significant research and utilization potential across various organs. However, there have been few studies on the phenolic content and antioxidant activity of different parts of pomegranate, especially the placenta. This study investigated the phenolic content and antioxidant activity of fruits, flowers, and leaves of two pomegranate varieties, ‘Tunisia’ and ‘Qingpi’, throughout their growth and development. Results indicated significant variations in phenolic content among different organs, with petals exhibiting the highest total polyphenol content (TPC, 49.40 mg GAE/g FW) and total anthocyanin content (TMAC, 1938.54 nmol/g FW). Placenta contained the highest levels of total flavonoids (TFC, 173.58 mg RE/g FW) and punicalagin (109.30 mg/g FW). The peel had the highest content of total flavanols (TFAC, 19.42 mg CE/g FW). Over the course of pomegranate development, total polyphenols, total flavonoids, total flavanols, punicalagin, and antioxidant activity declined in different organs. Antioxidant activity followed the order: fruit &gt; flower &gt; leaf, with the placenta exhibiting the highest antioxidant activity among fruits. Antioxidant activity showed a significant positive correlation with total polyphenols (R2 = 0.77-1.00), total flavonoids (R2 = 0.71-0.99, except tegmens), and punicalagin (R2 = 0.71-1.00). This study provides a comparative analysis of the phenolic content and antioxidant activity in different organs of pomegranate, highlighting the placenta as the primary source of punicalagin. This study provides a theoretical basis for the development and utilization of pomegranate phenolic compounds

Flexible operation of coal fired power plant integrated with post combustion CO2 capture using model predictive control

The growing demand for CO2 capture from coal-fired power plant (CFPP) has increased the need to improve the dynamic operability of the integrated power generation-CO2 capture plant. Nevertheless, high-level operation of the entire system is difficult to achieve due to the strong interactions between the CFPP and post combustion CO2 capture (PCC) unit. In addition, the control tasks of power generation and CO2 removal are in conflict, since the operation of both processes requires consuming large amount of steam. For these reasons, this paper develops a model for the integrated CFPP-PCC process and analyzes the dynamic relationships for the key variables within the integrated system. Based on the investigation, a centralized model predictive controller is developed to unify the power generation and PCC processes together, involving the key variables of the two systems and the interactions between them. Three operating modes are then studied for the predictive control system with different focuses on the overall system operation; power generation demand tracking and satisfying the CO2 capture requirement. The predictive controller can achieve a flexible operation of the integrated CFPP- PCC system and fully exert its functions in power generation and CO2 reduction