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关键词： NK cell   Graft versus leukemia   Graft versus host disease   Missing ligands   Major histocompatibility complex  

摘要： Background: Natural killer (NK) cells express killer immunoglobulin-like receptors (KIRs), which regulate their functions. Self-human leukocyte antigens (HLA) class I molecules act as inhibitory molecules for KIRs, blocking the killing activity of NK cells. Since normal NK activity may affect the outcomes of hematopoietic stem cell transplantation (HSCT) or bone marrow transplantation (BMT) from their HLA-matched sibling donors, we investigated the interaction between KIRs and class I HLA presented on NK cells. Complications such as graft-versus-host disease (GvHD) or transplant rejection may result because of deficient expression of class I HLA ligand inhibitors in the transplant recipient. Methods: We examined the effect of missing KIR ligands (MSL) and KIR haplotypes on GvHD development, relapses, death, infections, and cell recovery in HSCT patients. Our group included 59 patients [n = 24 with acute myeloid leukemia (AML), n = 12 with chronic myeloid leukemia (CML), n = 12 with myelodysplastic syndrome (MDS), and n = 11 with acute lymphoblastic leukemia (ALL)], who received HSCT/BMT from their sibling donors. Results: Our results showed that haplotype AA was more common than Bx in donors for patients with MDS and was associated with a higher incidence of chronic (c) GvHD (p = 0.003). In this group, we also observed a statistically significant relationship between the AA donor haplotype and absolute neutrophil count reconstruction of 0.5 G/l (0.5 x 109 cells/L) under 28 days (p = 0.03). Our results also showed an excellent correlation between KIR MSL values and cGvHD in AML patients (r = 0.9932). Conclusion: Our results indicate that KIR/HLA class I analysis at the stage of selection of a related donor could have an impact on the results of hematological transplantation and possibly reduce complications.

关键词： chondrocyte   interleukin‑1β   isorhamnetin   nuclear factor‑κB   osteoarthritis  

摘要： Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that certain of the western blot data shown in Fig. 3B on p. 4256 were strikingly similar to data that had already appeared in a paper written by different authors at different research institutes that had already been published in the journal . In view of the fact that the abovementioned data had already apparently been published prior to its submission to , the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [Molecular Medicine Reports 16: 4253‑4258, 2017; DOI: 10.3892/mmr.2017.7041].

关键词： Dengue infection   Tumor necrosis factor   Severe dengue   Immunoglobulin   Immune markers  

摘要： Dengue fever (Dengue Virus, Arbovirus) results in severe illness with mortality and morbidity, caused by any of four Dengue serotypes which results in a range of clinical manifestations. The sequence of infections can be an important cause of dengue severity. Early prediction of the high risk of complications in Dengue is dynamic and important to avoid hospital overcrowding during dengue epidemics. Multiple immune markers play a vital role in disease progression Primarily, TNF stimulates the production of reactive oxygen species resulting in cell death. The present study has an ideal design for identifying the risk factors of severity in dengue. Seven different biomarkers namely, TNF-alpha, TNFRSF7/CD27, TNFRSF9/CD137, TRAIL/TNFSF10, TNFRSF6B/DcR3, TNFSF6/Fas ligand and Fas/TNFRSF6/CD95, were evaluated in this study. Significantly, the level of TNFRSF7/CD27 in the dengue groups dengue without warning signs (D-W), dengue with warning signs (D + W), and severe dengue (SD) was higher than in the control group. Moreover, significant changes in the biomarker levels of TNFRS9/ CD137, TRAIL/TNFSF10, and TNFRSF6B/DcR3 were observed in the DI and SD groups as compared to healthy control group. In addition, the TNF alpha marker levels were significantly greater in the D-W group than in the healthy control group. However, biomarkers such as TNFRSF6/CD95, and TNFSF6/Fas ligand were markedly elevated in all the dengue (D-W, D + W, and SD) groups as compared to healthy control. The present study identifies these biomarkers that are differently expressed among D-W, D + W and subsequently augmented in SD.

关键词： Lung cancer   Radiation bystander effect   Intestinal injury   Isoliquiritigenin   TNF-alpha  

摘要： To construct a model of intestinal injury induced by radiotherapy for lung cancer and to study the protective effect and mechanism of isoliquiritigenin. The lungs of mice were irradiated with 0, 2, 4, 6, 8 Gy X-rays to screen the optimal radiation dose. A mouse model of lung cancer was established, and the tumor was irradiated once. At 3, 7, and 10 days after irradiation, H&E was used to detect the pathological manifestations of colon tissue in mice, and WB was used to detect the expression level of tight junction protein in colon tissue, so as to screen the best time point and study its possible mechanism. Molecular docking was used to study the tightness of isoliquiritigenin binding to TNF-alpha. Isoliquiritigenin (40 mg/kg) was given on the next day after 4 Gy X-ray irradiation. The levels of TNF-alpha and apoptosis, intestinal mucosal barrier function, MUC2 protein expression, and colon stem cell proliferation were detected. 4Gy X-ray local irradiation induced obvious colon injury in mice, and the injury was obvious on the 7th day. Isoliquiritigenin significantly improved the general condition, colonic histopathological changes, intestinal stem cell proliferation, and colonic tight junction function of lung cancer-bearing mice after radiotherapy. Further studies have found that isoliquiritigenin can downregulate the activation of TNF-alpha/Caspase-3 signaling pathway by inhibiting the expression of pro-inflammatory factor TNF-alpha, alleviate the apoptosis of colonic epithelial cells, improve the upregulation of colonic tight junction function, regulate the expression of MUC2, and promote the proliferation of intestinal stem cells, which may be related to the stable binding of isoliquiritigenin to TNF-alpha. Radiotherapy-induced bystander effect of lung cancer may be related to the abnormal expression of TNF-alpha. Isoliquiritigenin may downregulate the expression of TNF-alpha by binding to TNF-alpha, inhibit the apoptosis of colon cells, promote the proliferati

摘要： Targeting inflammation has emerged as a promising strategy to reduce residual cardiovascular risk. A study now uses human genetics to show that IL-6 inhibition is associated with a lower risk of cardiovascular disease with no increase in infection, supporting the use of pharmacological treatments that target IL-6 rather than its receptor. © Springer Nature Limited 2025.

关键词： conservation genomics   gene duplication   genetic architecture   incomplete lineage sorting   major histocompatibility complex   pit viper snakes  

摘要： Conservation of threatened species can benefit from an evaluation of genes in the major histocompatibility complex (MHC), whose loci encode proteins that bind pathogens and are often under strong selection to maintain diversity in immune response to diseases. Despite this gene family's importance to disease resistance, little is known about these genes in reptiles including snakes. To address this issue, we assembled and annotated a highly contiguous genome assembly for the timber rattlesnake (Crotalus horridus), a pit viper which is threatened or endangered in parts of its range, and analyzed this new genome along with three other rattlesnake genomes to characterize snake MHC loci. We identified highly duplicated MHC Class I and Class II beta genes in all species typified by a genomic architecture of discrete gene clusters localized on chromosome 2. The number of loci varied between species from 14 to 23 for MHC I and from 8 to 32 for MHC II beta and was greater than previously identified in the few non-genome-based studies of reptile MHC to date. We present evidence of the gene family's complex evolutionary history, with extensive duplication and loss concurrent with speciation resulting in incomplete lineage sorting. The differences in gene number between species combined with a dynamic evolutionary history suggest that gene family expansion/contraction via rapid duplication/gene loss may represent an important mechanism for generating genetic diversity in rattlesnake MHC. Our work demonstrates the utility of whole-genome sequences for identifying functional genetic variation in the form of MHC genes relevant for conservation genomic studies in threatened snakes.

关键词： AAV   adeno-associated virus   ABM   Ascl1, Brn2 and Myt1l   AD   Alzheimer disease   ADRC   adipose-derived regenerative cell   AI   artificial intelligence   ALS   amyotrophic lateral sclerosis   AMD   age-related macular degeneration   ASO   antisense oligonucleotide   ATMP   advanced therapy medicinal product   BBB   blood–brain barrier   BM   basement membrane   BDNF   brain-derived neurotrophic factor   BP-NCD   branched polyethyleneimine coated nitrogen-enriched carbon dots   BrdU   Bromodeoxyuridine   CD-AOF   chemically defined animal origin–free   CiPSC   chemically induced pluripotent stem cell   CNS   central nervous system   2D   2-dimensional   3D   3-dimensional   DMD   Duchenne muscular dystrophy   ECM   extracellular matrix   EGR2   early growth response protein 2   EMT   epithelial-to-mesenchymal transition   EPI   epiblast   ESC   embryonic stem cell   EV   extracellular vesicle   FAD   familial Alzheimer disease   FDA   US Food and Drug Administration   FGF   fibroblast growth factor   FNLM   FH-peptide-modified neutrophil-mimicking membrane   GMT   GATA4, MEF2C and TBX5   HCV   hepatitis C virus   HDF   human dermal fibroblast   hESC   human embryonic stem cell   HFF   human foreskin fibroblast   HIP   hypoimmune induced pluripotent stem cell   hiPSC   human induced pluripotent stem cell   hPSC   human pluripotent stem cell   HLA   human leukocyte antigen   HSC   hematopoietic stem cell   hUC   human urine cell   iCM   induced cardiomyocyte   ICM   inner cell mass   iHep   induced hepatocyte   IL   interleukin   ILC   innate lymphoid cell   iN   induced neuron   iPSC   induced pluripotent stem cell   iPSC-CM   induced pluripotent stem cell–derived cardiomyocyte   IRD   inherited retinal disease   LQTS   long-QT syndrome   MEF   mouse embryonic fibroblast   MG   Müller glia   MI   myocardial infarction   ML   machine learning   miR   microRNA   MPS   microphysiological system   MSC   mesenchymal stem cell   MST   MYOCD, SMAD6 and TBX20   MT   MEF2C and TBX5   mtDNA   mitochondrial DNA   MuSC   muscle stem cell   NCC   neural crest cell   NeuroD1   neuronal differentiation 1   NK   natural killer   NMJ   neuromuscular junction   NSC   neural stem cell   OCA   oculocutaneous albinism   OSK   Oct3/4, Sox2, Klf4   OSKM   Oct3/4, Sox2, Klf4, c-Myc   OPC   oligodendrocyte pro  

摘要： Recent advancements in cell and tissue biology have fundamentally changed our understanding of cellular behavior, revealing that both stem and nonstem cells exhibit remarkable plasticity and adaptability. This discovery has paved the way for revolutionary medical drug therapies that leverage cell and tissue reprogramming to repair or regenerate damaged tissues, offering new hope for conditions that were once considered irreversible. Tissue reprogramming involves the activation of specific molecular pathways to convert the function of residual tissue to compensate for the loss of tissue function to aging, trauma, or disease processes. By targeting these pathways, emerging drugs can promote regenerative processes, enabling the restoration of tissue function lost due to aging, injury, or disease. These therapies have shown promising results in preclinical studies addressing a wide range of diseases. Unlike traditional treatments, which focus primarily on managing symptoms, tissue reprogramming therapies offer a dynamic approach that can fundamentally alter cellular states, leading to functional recovery. This review explores the current state of cell and tissue reprogramming, highlighting its potential applications in regenerative medicine and the challenges that must be addressed for successful clinical translation. As our understanding of cellular plasticity continues to evolve, these innovative therapies stand at the forefront of a new era in medicine, with the potential to transform treatment paradigms and significantly improve patient outcomes across a wide range of conditions. Significance Statement: Breakthrough technologies have transformed our understanding of cell and tissue biology, uncovering that cells and tissues possess remarkable adaptability and fluidity in their roles. This revelation has opened up exciting possibilities in regenerative medicine, where emerging drug therapies aim to harness and reprogram cells to repair or regenerate damaged tissues.