In this article,we comment on an article published in a recent issue of the World Journal of Gastroenterology.We specifically focus on the roles of human leukocyte antigen(HLA)and donor-specific antibodies(DSAs)in pediatric liver transpl-antation(LT),as well as the relationship between immune rejection after LT and DSA.Currently,LT remains the standard of care for pediatric patients with end-stage liver disease or severe acute liver failure.However,acute and chronic re-jection continues to be a significant cause of graft dysfunction and loss.HLA mismatch significantly reduces graft survival and increases the risk of acute rejection.Among them,D→R one-way mismatch at three loci was significantly related to graft-versus-host disease incidence after LT.The adverse impact of HLA-DSAs on LT recipients is already established.Therefore,the evaluation of HLA and DSA is crucial in pediatric LT.
Monocyte-to-M0/M1 macrophage differentiation with unclear molecular mechanisms is a pivotal cellular event in many cardiovascular diseases including atherosclerosis.Long non-coding RNAs(lncRNAs)are a group of protein expression regulators;however,the roles of monocyte-lncRNAs in macrophage differentiation and its related vascular diseases are still unclear.The study aims to investigate whether the novel leukocyte-specific lncRNA Morrbid could regulate macrophage differentiation and atherogenesis.We identified that Morrbid was increased in monocytes and arterial walls from atherosclerotic mouse and from patients with atherosclerosis.In cultured monocytes,Morrbid expression was markedly increased during monocyte to M0 macrophage differentiation with an additional increase during M0 macrophage-to-M1 macrophage differentiation.The differentiation stimuli-induced monocyte-macrophage differentiation and the macrophage activity were inhibited by Morrbid knockdown.Moreover,overexpression of Morrbid alone was sufficient to elicit the monocyte-macrophage differentiation.The role of Morrbid in monocyte-macrophage differentiation was also identified in vivo in atherosclerotic mice and was verified in Morrbid knockout mice.We identified that PI3-kinase/Akt was involved in the up-regulation of Morrbid expression,whereas s100a10 was involved in Morrbid-mediated effect on macrophage differentiation.To provide a proof of concept of Morrbid in pathogenesis of monocyte/macrophage-related vascular disease,we applied an acute atherosclerosis model in mice.The results revealed that overexpression of Morrbid enhanced but monocyte/macrophage-specific Morrbid knockout inhibited the monocytes/macrophages recruitment and atherosclerotic lesion formation in mice.The results suggest that Morrbid is a novel biomarker and a modulator of monocyte-macrophage phenotypes,which is involved in atherogenesis.
Background and aim Hepatic ischemia–reperfusion injury(IRI)is a significant challenge in liver transplantation,trauma,hypovolemic shock,and hepatectomy,with limited effective interventions available.This study aimed to investigate the role of leukocyte cell-derived chemotaxin 2(LECT2)in hepatic IRI and assess the therapeutic potential of Lect2-short hairpin RNA(shRNA)delivered through adeno-associated virus(AAV)vectors.Materials and methods This study analyzed human liver and serum samples from five patients undergoing the Pringle maneuver.Lect2-knockout and C57BL/6J mice were used.Hepatic IRI was induced by clamping the hepatic pedicle.Treatments included recombinant human LECT2(rLECT2)and AAV-Lect2-shRNA.LECT2 expression levels and serum biomarkers including alanine aminotransferase(ALT),aspartate aminotransferase(AST),creatinine,and blood urea nitrogen(BUN)were measured.Histological analysis of liver necrosis and quantitative reverse-transcription polymerase chain reaction were performed.Results Serum and liver LECT2 levels were elevated during hepatic IRI.Serum LECT2 protein and mRNA levels increased post reperfusion.Lect2-knockout mice had reduced weight loss;hepatic necrosis;and serum ALT,AST,creatinine,and BUN levels.rLECT2 treatment exacerbated weight loss,hepatic necrosis,and serum biomarkers(ALT,AST,creatinine,and BUN).AAV-Lect2-shRNA treatment significantly reduced weight loss,hepatic necrosis,and serum biomarkers(ALT,AST,creatinine,and BUN),indicating therapeutic potential.Conclusions Elevated LECT2 levels during hepatic IRI increased liver damage.Genetic knockout or shRNA-mediated knockdown of Lect2 reduced liver damage,indicating its therapeutic potential.AAV-mediated Lect2-shRNA delivery mitigated hepatic IRI,offering a potential new treatment strategy to enhance clinical outcomes for patients undergoing liver-related surgeries or trauma.
According to the latest global cancer statistics,colorectal cancer(CRC)has emerged as the third most prevalent malignant tumor across the globe.In recent decades,the medical field has implemented several levels of CRC screening tests,encompassing fecal tests,endoscopic examinations,radiological examinations and blood tests.Previous studies have shown that leukocyte immunoglobulin-like receptor B2(LILRB2)is involved in inhibiting immune cell function,immune evasion,and promoting tumor progression in acute myeloid leukemia and nonsmall cell lung cancer.However,its interaction with CRC has not been reported yet.Recently,a study published in the World Journal of Gastroenterology revealed that LILRB2 and its ligand,angiopoietin-like protein 2,are markedly overexpressed in CRC.This overexpression is closely linked to tumor progression and is indicative of a poor prognosis.The study highlights the potential of utilizing the concentration of LILRB2 in serum as a promising biomarker for tumors.However,there is still room for discussion regarding the data processing and analysis in this research.
Objective:To investigate the molecular mechanism and identify potential drugs for subthreshold depression(SD),and elucidate the detalied mechanism of Danzhi Xiaoyao powder(DZXY)in SD.Methods:Using RNA-sequencing,we identified differentially expressed genes(DEGs)in leukocytes of SD compared to healthy controls,deciphered their functions and pathways,and identified the hub genes of SD.We also assessed changes in leukocyte transcription factor activity in patients with SD using the TELis platform.The Connectivity Map database was retrieved to screen candidate drugs for SD.Based on network pharmacology,we elucidated the"multi-component,multi-target,and multi-pathway"mechanism of DZXY in the treatment of SD.Results:We identified 1080 DEGs(padj<0.05 and|log2(fold change)l≥1&protein coding)in the leukocytes of patients with SD.These DEGs,including hub genes,were primarily involved in immune and inflammatory response-related processes.Transcription factor activity analysis revealed similarities between the leukocyte transcriptome profile in SD and the conserved transcriptional response to adversities in immune cells.Connectivity Map analysis identified 28 potential drugs for SD treatment,particularly SB-202190 and TWS-119.Constructing the"Direct Compounds-Direct Targets-Pathways"network for DZXY and SD revealed the curative mechanisms of DZXY in SD,primarily including inflammatory response,lipid metabolism,immune response,and other processes.Conclusion:These results provide new insights into the characteristics and functional changes of leukocytes in SD,partially illustrate the pathogenesis of SD,and suggest potential drugs for SD.The curative mechanisms of DZXY in SD are also partially elucidated.
Objective Diabetic foot ulcer(DFU)is one of the most serious complications of diabetes.Leukocyte-and platelet-rich fibrin(L-PRF)is a second-generation autologous platelet-rich plasma.This study aims to investigate the clinical effects of L-PRF in patients with diabetes in real clinical practice.Methods Patients with DFU who received L-PRF treatment and standard of care(SOC)from 2018 to 2019 in Tongji Hospital were enrolled.The clinical information including patient characteristics,wound evaluation(area,severity,infection,blood supply),SOC of DFU,and images of ulcers was retrospectively extracted and analyzed.L-PRF treatment was performed every 7±2 days until the ulcer exhibited complete epithelialization or an overall percent volume reduction(PVR)greater than 80%.Therapeutic effectiveness,including overall PVR and the overall and weekly healing rates,was evaluated.Results Totally,26 patients with DFU were enrolled,and they had an ulcer duration of 47.0(35.0,72.3)days.The severity and infection of ulcers varied,as indicated by the Site,Ischemia,Neuropathy,Bacterial Infection,and Depth(SINBAD)scores of 2–6,Wagner grades of 1–4,and the Perfusion,Extent,Depth,Infection and Sensation(PEDIS)scores of 2–4.The initial ulcer volume before L-PRF treatment was 4.94(1.50,13.83)cm3,and the final ulcer volume was 0.35(0.03,1.76)cm3.The median number of L-PRF doses was 3(2,5).A total of 11 patients achieved complete epithelialization after the fifth week of treatment,and 19 patients achieved at least an 80%volume reduction after the seventh week.The overall wound-healing rate was 1.47(0.63,3.29)cm3/week,and the healing rate was faster in the first 2 weeks than in the remaining weeks.Concurrent treatment did not change the percentage of complete epithelialization or healing rate.Conclusion Adding L-PRF to SOC significantly improved wound healing in patients with DFU independent of the ankle brachial index,SINBAD score,or Wagner grade,indicating that this method is appropriate for DFU treatment under different clinical con
Leukocyte immunoglobulin‐like receptor B4(LILRB4)significantly impacts immune regulation and the pathogenesis and progression of various cancers.This review discusses LILRB4's structural attributes,expression patterns in immune cells,and molecular mechanisms in modulating immune responses.We describe the influence of LILRB4 on T cells,dendritic cells,NK cells,and macrophages,and its dual role in stimulating and suppressing immune activities.The review discusses the current research on LILRB4's involvement in acute myeloid leukemia,chronic lymphocytic leukemia,and solid tumors,such as colorectal cancer,pancreatic cancer,non‐small cell lung cancer,hepatocellular carcinoma,and extramedullary multiple myeloma.The review also describes LILRB4's role in autoimmune disorders,infectious diseases,and other conditions.We evaluate the recent advancements in targeting LILRB4 using monoclonal antibodies and peptide inhibitors and their therapeutic potential in cancer treatment.Together,these studies underscore the need for further research on LILRB4's interactions in the tumor microenvironment and highlight its importance as a therapeutic target in oncology and for future clinical innovations.