Objective To summarize and analyze the efficacy and influencing factors of second allogeneic hematopoietic stem cell transplantation (allo-HSCT) for acute leukemia relapsing after the first allo-HSCT. Methods Clinical data of 17 patients with acute leukemia who underwent second allo-HSCT at Peking University First Hospital from January 2005 to December 2024 were retrospectively analyzed. Results Among the 17 patients, 7 achieved long-term disease-free survival after second transplantation. The median progression-free survival after successful second transplantation was 7 months (range 8 days to 69 months). The relapse fatality was 24%, and the transplant-related fatality was 35%. Conclusions Second transplantation is an effective treatment for relapsed and refractory acute leukemia, but the relapse fatality and transplant-related fatality remain high. Patient age, time of relapse after the first transplantation and disease status before second transplantation are all factors that affect the efficacy of second transplantation. Younger age, late relapse and complete remission of disease before second transplantation are all beneficial for long-term disease-free survival after second transplantation.

[This corrects the article DOI: 10.1016/j.apsb.2022.05.019.].

Osteoarthritis (OA) causes chronic pain that significantly impairs quality of life, with current treatments often proving insufficient and accompanied by adverse effects. Recent research has identified the dorsal root ganglion (DRG) and its resident macrophages as crucial mediators of chronic OA pain through neuroinflammation driven by macrophage polarization. We present a novel injectable thermo-sensitive hydrogel system, KAF@PLEL, designed to deliver an anti-inflammatory peptide (KAF) specifically to the DRG. This biodegradable hydrogel enables sustained KAF release, promoting the reprogramming of DRG macrophages from pro-inflammatory to anti-inflammatory phenotypes. Through comprehensive in vitro and in vivo studies, we evaluated the hydrogel's biocompatibility, effects on macrophage polarization, and therapeutic efficacy in chronic OA pain management. The system demonstrated significant capabilities in preserving macrophage mitochondrial function, suppressing neuroinflammation, alleviating chronic OA pain, reducing cartilage degradation, and improving motor function in OA rat models. The sustained-release properties of KAF@PLEL enabled prolonged therapeutic effects while minimizing systemic exposure and side effects. These findings suggest that KAF@PLEL represents a promising therapeutic approach for improving outcomes in OA patients through targeted, sustained treatment.

N⁶-methyladenosine (m⁶A) modification plays a critical role in cell cycle regulation, while the mechanism of m⁶A in regulating mitosis remains underexplored. Here, we found that the total m⁶A modification level in cells increased during mitosis by the liquid chromatography-mass spectrometry/mass spectrometry and m⁶A dot blot assays. Silencing methyltransferase-like 3 (METTL3) or METTL14 results in delayed mitosis, abnormal spindle assembly, and chromosome segregation defects by the immunofluorescence. By analyzing transcriptome-wide m⁶A targets in HeLa cells, we identified polo-like kinase 1 (PLK1) as a key gene modified by m⁶A in regulating mitosis. Specifically, through immunoblotting and RNA pulldown, m⁶A modification inhibits PLK1 translation via YTH N⁶-methyladenosine RNA binding protein 1, thus mediating cell cycle homeostasis. Demethylation of PLK1 mRNA leads to significant mitotic abnormalities. These findings highlight the critical role of m⁶A in regulating mitosis and the potential of m⁶A as a therapeutic target in proliferative diseases such as cancer.
Humans ; Polo-Like Kinase 1 ; Cell Cycle Proteins/metabolism* ; Proto-Oncogene Proteins/metabolism* ; Protein Serine-Threonine Kinases/metabolism* ; Mitosis/physiology* ; HeLa Cells ; Adenosine/genetics* ; Methyltransferases/metabolism* ; RNA, Messenger/metabolism* ; RNA-Binding Proteins/metabolism*

Skeletal muscle injury is a common disease in clinical practice,and an in-depth understanding of its repair mechanisms is crucial for the development of effective therapeutic strategies.This paper focuses on the key role of TGF-β in skeletal muscle injury repair,introduces the diversity of its family members and signaling pathways,explores the expression and regulation part of TGF-β after skeletal muscle injury,analyzes its early expression dynamics and regulatory factors,and thoroughly investigates the effects of TGF-β on skeletal muscle repair,revealing its inflammatory regulation,cellular activation and proliferation as well as fibrosis.Key role.Special attention was paid to its mechanism of action in muscle regeneration and its regulatory mechanism at the cellular level.In addition,the potential clinical applications of TGF-β in the repair of skeletal muscle injury were discussed,and the development and application of it as a therapeutic target and modulator were explored.However,controversies and shortcomings still exist in the current study,such as the dual roles of TGF-β and the impact of individual differences on treatment.Future research directions should include digging deeper into the details of signaling pathways and biomarker discovery.By overcoming these challenges,the potential clinical application of TGF-β in skeletal muscle injury repair is expected to usher in new breakthroughs and provide patients with more individualized and effective treatment strategies.

Objective This study aimed to investigate the effects of P.odoratum extract on lactase activity and microflora diversity in mice with bacterial dysbacteriosis.Methods SPF male BALB/c mice were randomized into 4 groups:control,model,P.odoratum extract low dose(1.56 g·kg-1·d-1)and high dose(3.12 g·kg-1·d-1)treatment group.There were 8 mice in each group(5 in the blank group).In addition to the control group,after 7 days of intragastric administration of mixed antibiotics,the administration groups were given P.odoratum extract for 7 days,and the control group and the model group were given the same amount of sterile water.The changes of diarrhea,body weight and food intake of mice were recorded.The colon HE staining sections,ZO-1 protein,IL-6 expression,and serum LPS concentration were detected.Feces were collected for lactase activity and microbial diversity determination with 16S rRNA high-throughput sequencing technology.Results After 7 days of antibiotic intervention,compared with the control group,the mice in the model group had soft stool,weight loss,reduced food intake,and significantly reduced intestinal flora diversity.At the 14th day,in the model group,ulceration accompanied by slight interstitial congestion and edema was seen in the colon,ZO-1 expression was significantly reduced,IL-6 expression was significantly increased,serum LPS was significantly increased,lactase activity was significantly reduced,and intestinal flora diversity was still lower compared with the control group.After 7 days of administration,compared with the model group,P.odoratum reduced the diarrhea rate of mice,promoted a recovery of body weight and food intake,downregulated pathological colon tissue damage,significantly increased ZO-1 protein expression,and reduced colon factor IL-6 and serum LPS concentration.In addition,P.odoratum can significantly up-regulate lactase activity and improve the community richness and diversity of dysbacteriosis mice.It is shown that three phyla(up-regulated Firmicutes,down-regulated Proteobacteria and Bacteroidetes)and seven genera(up-regulated Rikenellaceae_RC9_gut_group,Rikenella,Colidextribacter,norank_f__Lachnospiraceae,norank_f__Oscillospiraceae,and Lachnospiraceae_NK4A136_group,down-regulated Alloprevotella),the abundance of which was significantly correlated with body weight and lactase activity,serum LPS,and colon factor IL-6.Conclusion P.odoratum can alleviate the gut barrier injury and dysfunction caused by antibiotic induced dysbiosis,and its mechanism may be achieved by regulating microflora structure.

Objective To investigate the effects of indirubatin derivative E804 on proliferation and migration of non-small cell lung cancer(NSCLC)A549 cells,and to elucidate the possible mechanism of Nrf2-HO-1/GPX4 pathway.Methods Lung cancer A549 cells were used as the cell model.The proliferation and migration of differ-ent specific inhibitors(Nec-1,CQ,Z-VAD,DFO,Fer-1 and Lip-1)in 0,10 μmol/L E804 and 10 μmol/L E804+groups were observed by MTT and cell scratch assay.The contents of reactive oxygen species(ROS)were de-tected by DCFH-DA fluorescence probe method,the contents of Fe2+were detected by colorimetric method,the contents of reduced glutathione(GSH)were detected by spectrophotometry,and the contents of malondialdehyde(MDA)were detected by micromethod.The expression levels of SLC7A11,Transferrin,GPX4,SLC40A1,Nrf2 and HO-1 were detected by Western blot in cells of 0,2.5,5 and 10 μmol/L E804 groups.Results Compared with the control group(0 μmol/L E804),2.5,5 and 10 μmol/L E804 significantly increased intracellular ROS,Fe2+and MDA levels,and decreased intracellular GSH content(P＜0.01).Meanwhile,the expression levels of SLC7A11,GPX4,SLC40A1,Nrf2 and HO-1 significantly decreased(P＜0.01),and the expression level of Transferrin increased(P＜0.05).Compared with the 10 μmol/L E804 group alone,the apoptosis inhibitor(Z-VAD)group and the ferroptosis inhibitor(DFO,Fer-1 and Lip-1)group could significantly reverse the inhibition of proliferation and migration of A549 cells by 10 μmol/L E804(P＜0.01).Conclution E804 can induce ferrop-tosis and inhibit the proliferation and migration of A549 cells,which may be related to the inhibition of Nrf2-HO-1/GPX4 pathway.

Metabolic reprogramming is a hallmark of cancer, including lung cancer. However, the exact underlying mechanism and therapeutic potential are largely unknown. Here we report that protein arginine methyltransferase 6 (PRMT6) is highly expressed in lung cancer and is required for cell metabolism, tumorigenicity, and cisplatin response of lung cancer. PRMT6 regulated the oxidative pentose phosphate pathway (PPP) flux and glycolysis pathway in human lung cancer by increasing the activity of 6-phospho-gluconate dehydrogenase (6PGD) and α-enolase (ENO1). Furthermore, PRMT6 methylated R324 of 6PGD to enhancing its activity; while methylation at R9 and R372 of ENO1 promotes formation of active ENO1 dimers and 2-phosphoglycerate (2-PG) binding to ENO1, respectively. Lastly, targeting PRMT6 blocked the oxidative PPP flux, glycolysis pathway, and tumor growth, as well as enhanced the anti-tumor effects of cisplatin in lung cancer. Together, this study demonstrates that PRMT6 acts as a post-translational modification (PTM) regulator of glucose metabolism, which leads to the pathogenesis of lung cancer. It was proven that the PRMT6-6PGD/ENO1 regulatory axis is an important determinant of carcinogenesis and may become a promising cancer therapeutic strategy.

Liver transplantation is a vital treatment for end-stage liver disease. However, the shortage of donor livers has limited the development of liver transplantation. How to expand the source of donor livers has become a challenge in the academic community. In recent years, the proportion of donors with non-alcoholic fatty liver disease (NAFLD) has been increased. Rational use of steatotic donor livers is a feasible approach to expand the donor pool. Cold ischemia injury during donor liver preservation before liver transplantation increases the risk of postoperative organ dysfunction. Therefore, it is of significance to unravel the mechanism and intervention measures of cold ischemia injury of steatotic donor livers. Cold ischemia injury of steatotic donor livers is characterized as the damage of mitochondria, lysosomes and endoplasmic reticulum at the organelle level, and up-regulated expression of adenosine monphosphate activated protein kinase (AMPK), aldehyde dehydrogenase 2 (ALDH2) and heme oxygenase (HO)-1 at the protein level. In this article, the research progresses on cold ischemia injury of steatotic donor livers and relevant intervention measures were reviewed.