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The bone marrow microenvironment, also known as the bone marrow niche, plays a critical role in maintaining the functions of hematopoietic stem cells. Under physiological conditions, various bone marrow cells regulate each other to sustain hematopoietic homeostasis. However, bone marrow cells gain abnormal function under pathological conditions to cause and promote the occurrence of leukemia and induce drug resistance. Recent findings indicate that abnormal proliferation and differentiation are not the sole reason to cause leukemia. Different types of bone marrow cells also induce intercellular adhesion, abnormally secrete cytokines and chemokines, accelerating leukemia's progress. This article reviews the multiple signaling pathways that regulate the formation and progress of leukemia bone marrow niche, such as C-X-C motif chemokine ligand 12/C-X-C motif chemokine receptor 4 signaling pathway, et al. It emphasizes that targeting leukemia bone marrow niche is a vital strategy for improving the leukemia treatment.
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Background: Immunoglobulin G4-related disease (IgG4-RD) is an immune mediated fibro inflammatory condition characterized by abundant IgG4-positive (IgG4+) plasma cell infiltrated lesions and elevated serum IgG4 concentrations. Tubulointerstitial nephritis and glomerular lesions are the most common renal IgG4-RDs. However, solitary mass lesion is rarely observed in renal IgG4-RD. Materials and Methods: We reported a 55-year-old male patient with a space-occupying lesion in the right kidney detected during a routine ultrasound medical examination. Computed tomography indicated a 20 mm × 15 mm × 18 mm mass located at the lower pole of the right kidney. Both T1-weighted imaging and T2-weighted imaging magnetic resonance imaging scans showed a hypointense mass. Diffusion-weighted imaging (b value = 800) showed slightly hyperintensity. Results: The lesion was diagnosed as renal cell carcinoma clinically based on the laboratory and radiological findings and treated with laparoscopic resection. However, the postoperative histological examination results indicated the lesion IgG4-RD of the kidney. Conclusion: We should consider pseudotumor-like IgG4-RD as a differential diagnosis for solitary renal lesion although the incidence is low
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Philadelphia chromosome (Ph) positive (Ph+) B cell acute lymphoblastic leukemia (B-ALL) is the most common genetic abnormality associated with B-ALL and has been shown to confer the worst prognosis to both children and adults. Increasing evidence has revealed that high tribbles homologue 3 (TRIB3) expression contributes to multi-cancer development and progression, but the underlying role and molecular mechanisms of TRIB3 in Ph+ B-ALL remain unclear. Here, we report that TRIB3 expression was enhanced in Ph+ B-ALL patient samples and positively associated with the expression of breakpoint cluster region-Abelson tyrosine kinase (BCR-ABL). We further demonstrated that deletion of TRIB3 attenuated the progression of Ph+ B-ALL by reducing BCR-ABL expression. Mechanistically, TRIB3 interacted with lysosomal cysteine proteinase cathepsin Z (CTSZ) to suppress CTSZ-mediated BCR-ABL degradation, which enhanced BCR-ABL activity, causing high proliferation of Ph+ B-ALL cells. Thus, our study indicated that inhibiting the expression of TRIB3 to regulate BCR-ABL kinase activity may be exploited as an additional target therapy for Ph+ ALL. Procedures for animal study were performed with approval of the Animal Care and Use Committee of the Chinese Academy of Medical Sciences and Peking Union Medical College. The procedure of human leukemia sample was approved by the Ethics Committee of Chinese Academy of Medical Sciences and Peking Union Medical College (KT2019055-EC-1).
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<p><b>OBJECTIVE</b>To evaluate the application of different variable number tandem repeats (VNTR) locus in genotyping of Mycobacterium tuberculosis (M.tuberculosis) strains isolated from eight provinces in China, and to find the suitable locus-set of VNTR for epidemical strains in China.</p><p><b>METHODS</b>All 140 M.tuberculosis strains were randomly selected from 2800 M.tuberculosis strains isolated from eight provinces in China, 27 VNTR loci were used for typing all isolates. Discriminatory power (Hunter-Gaston Index, HGI) of every locus and different locus-set were analyzed by BioNumerics software. Meanwhile, Spoligotyping was used to identify Beijing family and non-Beijing family. Then the HGI of different locus-sets in two families was also evaluated.</p><p><b>RESULTS</b>All 140 isolates were clustered into Beijing kindred (112 strains, 80%) and non-Beijing kindred (28 strains, 20%) by Spoligotyping. The discriminatory power of Spoligotyping in 140 isolates was 0.4589. Every locus showed different polymorphism and HGI were from 0 to 0.809. The number of VNTR loci with HGI higher than 0.5 in all strains, Beijing family and non-Beijing family was 8, 7 and 14 respectively. 27 loci were combined into four groups which included 8, 12, 15 and 24 VNTR loci respectively. Four locus-sets showed different polymorphism, HGI of eight-locus, 12-locus, 15-locus, and 24-locus set in 140 strains was 0.9991, 0.9882, 0.9980 and 0.9986, and their discriminatory power were calculated in Beijing kindred (HGI: 0.9987, 0.9318, 0.9969 and 0.9975) and non-Beijing kindred (HGI: 1, 0.9894, 1 and 1).</p><p><b>CONCLUSION</b>Different VNTR locus and locus-set showed different discriminatory power in the selected M.tuberculosis strains isolated from China. Eight-locus set can be used in molecular epidemiological study of M.tuberculosis in China after standardization.</p>
Subject(s)
Bacterial Typing Techniques , DNA, Bacterial , Genetics , Mycobacterium tuberculosis , Classification , Genetics , Tandem Repeat SequencesABSTRACT
Objective To evaluate the discriminatory efficiency of multiple loci of variable numbers of tandem repeats (VNTR) in Mycobacterium tuberculosis genome.Genotyping and identification on Chinese M.tuberculosis clinical strains were used to locate a series of high discriminated loci,so as to provide the basis for creating a standardized multiple loci VNTR analysis (MLVA) to distribute fast typing and identification on Chinese M.tuberculosis.Methods VNTR loci which were chosen from the website http://minisatellites.u-psud.fr/ and referenced to the genome sequence of M.tuberculosis standard strain H37Rv were tested in Chinese M.tuberculosis clinical strains and H37Rv by means of PCR.The primers were designed by DNAStar software.The repeat member of VNTR unit was estimated by the result of PCR.The discrimination power of single locus or multiple loci was confirmed by the Hunter-Gaston index.Results 45 VNTR loci were tested in 135 Chinese M.tuberculosis clinical strains and H37Rv.The discrimination power of these loci appeared different from each other,with the biggest Hunter-Gaston index as 0.814 (0.797-0.830),the smallest one as 0.015 (0.001-0.028),and there were 13 loci with which the Hunter-Gaston index was bigger than 0.5.Results showed that the discrimination power was increasing by different loci that associated with each other.The more loci that were combined,the bigger the Hunter-Gaston index was,For example,the Hunter-Gaston index of Qub11-b associated with Qub 18 was 0.936,by which 136 strains could be divided into 44 groups.With the combination of 9 loci including Qub11-b,Qub18,Mtub21,Rv2372,MIRU26,Qub26,Qub4156c,Qub11-a and Qub15,the HunterGaston index could have reached 1 and by which the 136 strains could be divided into 136 groups,also showing that the biggest discrimination power to strain identification,viz.strain level genotype were reached.Conclusion The discrimination power of different locus was different.The discrimination power of multiple loci was much more satisfied than that of single locus.It was satisfied the combine discrimination power of 9 loci including Qubll-b,Qubl8,Mtub21,Rv2372,MIRU26,Qub26,Qub4156c,Qub11-a and Qubl5,by which the qualified typing method could gain to facilitate research on molecular epidemiology with the Hunter-Gaston index analysis.
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BACKGROUND: Chinese traditional osteopathy is long in history, unique in manipulation and miraculous in therapeutic effect. But people understand it more m perception rather than in theory, more in application rather than in development. There is little research truly on the bioseience.OBJECTIVE: To probe into the macro-idea of Chinese traditional osteopathy, micro-mechanisms on characters and mathematics-physics models, aiming to provide new principles and approaches of treatment for the daily increased bone trauma, fracture and sport injury.SETTING: Physics and machine-electron college of a university, and its affiliated hospital.METHODS: Based on the natural concept of "integration between heaven and human being" and new concept of holistic medicine in Chinese traditional osteopathy, the macro-idea and characters of reduction and union of fracture are generalized from the characters of natural therapy and the biomechanical mechanisms and characters of reduction and union of fracture are summarized from the micro-reaction of bone repair and union so as to discover biomechanical mechanisms and characters of reduction and union of fracture and further to set up biomechanical models and mathematics-physics expressions during the treatment.RESULTS: Chinese traditional osteopathy envelopes macro-idea of "initiative reduction-functional union" in fracture and micro-mechanism on "stress adaptability-functional adaptability" of bone repair and union.CONCLUSION: Chinese traditional osteopathy compiles with the natural,green and non-traumatic therapy in bio-natural law of bone repair and union and supports the theme of "high thought and high skill".