PubMed Health⌕ Search

Biomedical subjects

Xiaobo Li

Publications and source records attributed to Xiaobo Li.

12 recordsLinked to original sources
PubMed2026

Genomic and evolutionary basis of parthenogenesis in a disease-vector tick species.

Haemaphysalis longicornis is an important tick species and pathogen vector characterized by the co-circulation of triploid parthenogenetic and diploid bisexual strains. However, the evolutionary basis of parthenogenesis in this species is unclear. Here we report reference-quality, haplotype-resolved genome assemblies of the parthenogenetic strain and two reference-quality genomes of the bisexual strains. Comparative genomic analysis revealed high collinearity between the parthenogenetic and bisexual genomes, with a stable chromosomal architecture maintained among the three haplotypes of the parthenogenetic strain. The parthenogenetic H. longicornis genome exhibited a major expansion in cell cycle-related gene families, including the inhibitor of apoptosis protein (IAP) family, but was characterized by a contraction in other gene families. Population resequencing of 179 individuals revealed two distinct subpopulations, with chromosome 7 harbouring high genetic differentiation and several candidate genes probably associated with parthenogenesis. Functional experiments showed that knockdown of the BIRC5 gene, a member of the IAP family, suppressed oviposition in both strains, with the parthenogenetic strain exhibiting milder adverse effects probably due to a stronger transcriptional response. Overall, our results reveal the genomic and evolutionary features associated with polyploid parthenogenesis in H. longicornis.

Animals↗
PubMed2026

Targeting the METTL1/m7G axis as a therapeutic strategy in myeloid leukemia.

N7-methylguanosine (m7G), a prevalent modification in transfer RNAs (tRNAs), is primarily catalyzed by the methyltransferase METTL1. Although growing evidence supports a role for METTL1 in various tumors, its therapeutic potential and precise function in leukemia stem cell (LSC) homeostasis remain largely unexplored. Here, we identify METTL1 as a key regulator of LSC self-renewal and homing within bone marrow (BM) microenvironment through catalyzing m7G formation on a specific tRNA, tRNAPheGAA, thereby promoting leukemogenesis. Mechanistically, METTL1 loss significantly reduces m7G abundance and steady-state levels of tRNAPheGAA, leading to translation suppression and degradation of transcripts enriched with tRNAPheGAA-related codons, such as hematopoietic cell kinase (HCK). Decreased HCK expression disrupts CXCR4 signaling, impairing LSC self-renewal and BM homing. Therapeutically, we characterized a small-molecule METTL1 inhibitor (M1i; NSC137443), through high-throughput screening. Pharmacological inhibition of METTL1 demonstrated potent antitumor efficacy by reducing tRNA m7G levels and disrupting the tRNAPheGAA/HCK/CXCR4 cascade. Notably, targeting METTL1 significantly reduces LSC frequency, delays leukemogenesis, and prolongs survival in multiple acute myeloid leukemia models. Together, our findings establish a previously unrecognized role for METTL1 and its target tRNAPheGAA in LSC homeostasis and provide compelling proof-of-concept evidence that METTL1 is a druggable epitranscriptomic target for antileukemia therapy.

Humans↗
PubMed2006

A novel P755L mutation in LRRK2 gene associated with Parkinson's disease.

Parkinson's disease is a common neurodegenerative disorder. The identification of leucine-rich repeat kinase 2 (LRRK2) gene mutations as a cause of Parkinson's disease has greatly expanded our knowledge of the genetic and molecular pathogenesis of this disorder. By denaturing high-performance liquid chromatography and gene sequencing in patients and controls, we identified a novel frequent heterozygous 2264C-->T substitution, which causes a proline-to-leucine mutation (P755L) in LRRK2 gene. In our sample of 598 patients of Chinese Han ancestry, 12 cases carried the same LRRK2 mutation. Our results indicated that this single mutation was implicated in 2% of sporadic patients. We suggest that testing for this mutation will be important in the management and genetic counseling of patients with Parkinson's disease.

Adult↗
PubMed2006

Quantitative analysis along the pyramidal tract by length-normalized parameterization based on diffusion tensor tractography: application to patients with relapsing neuromyelitis optica.

In this study, we introduced a length-normalized parameterization method to establish anatomical correspondence of white matter fiber tracts across subjects and applied this method to investigate the presence of abnormal diffusion along the pyramidal tract (PYT) of relapsing neuromyelitis optica (RNMO) patients without visible brain lesions. In this approach, the part of the PYT between the lowest slice of the cerebral peduncle and the uppermost slice of the lateral ventricle was reconstructed to establish the anatomical correspondence across subjects using diffusion tensor tractography. Then it was parameterized by normalizing its length and dividing equally the normalized length into a certain number of segments, so that the comparability of each segment across subjects along the PYT was established. Tract-specific diffusion indices, including directionally averaged diffusivity (D(av)), fractional anisotropy (FA), primary diffusivity (lambda(1)) and transverse diffusivity (lambda(23)), were obtained from each segment. Thus, the distribution maps of these indices along the PYT were obtained. The distribution maps of D(av), FA, and lambda(23) of RNMO patients were significantly different from those of healthy controls, especially in the lower part of the PYT. The differences may be caused by secondary degeneration to lesions in the spinal cord. In conclusion, a length-normalized parameterization method is proposed to establish anatomical correspondence for the PYT. Compared with existed methods, a major merit of our method is to provide comparability across subjects along the PYT on the basis of diffusion tensor tractography and to make it possible for the quantitative analysis along the fiber tract. This method can also be used to quantitatively analyze other white matter fiber tracts between two definite anatomic landmarks in many neurological or psychiatric diseases.

Adult↗
PubMed2006

Effect of hypoxia/reoxygenation on CD73 (ecto-5'-nucleotidase) in mouse microvessel endothelial cell lines.

Cerebral ischemia and post-ischemic reperfusion commonly result in significant brain damage. Brain microvessel endothelial cells, the key target cells and regulating sites, can secrete adenosine which plays an important neuroprotective role in the ischemic brain. A primary determinant of localized production of adenosine at tissue interfaces is ecto-5'-nucleotidase (CD73). In our experiments, we used bEnd.3 cells, immortalized mouse brain microvessel endothelial cell lines, as the target cells to study the effect of hypoxia and posthypoxic reoxygenation on CD73 in brain microvessel endothelial cells. CD73 activity in bEnd.3 cells exposed to hypoxia significantly increased in time-dependent way. The upregulation of CD73 mRNA and protein expression induced by hypoxia in bEnd.3 cells were detected by RT-PCR and Western blot. However, for reoxygenation studies, CD73 activity, mRNA and protein expression decreased at the initial stages, but increased at prolonged reoxygenation. Our results suggest that hypoxia can induce upregulation of CD73 expression in brain microvessel endothelial cells, which can be reversed by reoxygenation of short duration. But CD73 expression increased gradually with the duration of reoxygenation. Then, we infer that CD73 in brain microvessel endothelial cells plays a very important role through forming adenosine during brain ischemia and reperfusion.

5'-Nucleotidase↗
PubMed2006

Genetic variability of Blastocystis hominis isolates in China.

To determine if genetic diversity of Blastocystis hominis exists in China, 35 B. hominis isolates obtained from 19 asymptomatic infected individuals and 16 patients with gastrointestinal symptoms were genotyped by PCR using seven pairs of known sequenced-tagged site (STS) primers. Out of the 35 isolates, 29 were identified as one of the known genotypes, while five isolates showed two distinct genotypes, and one isolate was an unknown genotype as this was negative with all the STS primers. In this study, none of the isolates was classified as subtypes 4-7. Compared with the spectrum of human B. hominis subtypes obtained from five geographically different countries (Japan, Pakistan, Bangladesh, Germany, and Thailand), these results showed that subtype 1 was more a popular genotype (18/35) in China. In addition, two groups of the isolates from 19 asymptomatic infected individuals and those from 16 patients with intestinal symptoms were compared with the PCR-based subtype classification. The results suggest a possible relationship between subtype 1 and a pathogenic potential of this parasite.

Animals↗
PubMed2006

Enzyme activity assay for cholesterol 27-hydroxylase in mitochondria.

Mitochondrial cholesterol 27-hydroxylase (CYP27A1) plays an important role in the maintenance of intracellular cholesterol homeostasis. Cholesterol delivery to the mitochondrial inner membrane is believed to be a rate-limiting step for the "acidic" pathway of bile acid synthesis. This work reports that proteinase K treatment of mitochondria markedly increases CYP27A1 specific activity. With endogenous mitochondrial cholesterol, treatment with proteinase K increased CYP27A1 specific activity by 5-fold. Moreover, the addition of the exogenous cholesterol in beta-cyclodextrin plus proteinase K treatment increased the specific activity by 7-fold. Kinetic studies showed that the increased activity was time-, proteinase K-, and substrate concentration-dependent. Proteinase K treatment decreased the apparent K(m) of CYP27A1 for cholesterol from 400 to 150 microM. Using this new assay, we found that during rat hepatocyte preparation and cell culture, mitochondria gradually lose CYP27A1 activity compared with mitochondria freshly isolated from rat liver tissue.

Animals↗
PubMed2006

Cholesterol, LDL, and 25-hydroxycholesterol regulate expression of the steroidogenic acute regulatory protein in microvascular endothelial cell line (bEnd.3).

The steroidogenic acute regulatory (StAR) protein promotes intramitochondrial delivery of cholesterol to the cholesterol side-chain cleavage system. In this experiment, we first demonstrated that StAR expressed in endothelial cells as well. Immunochemistry showed positive staining of StAR in endothelial cells. To investigate whether steroids and oxysterols regulate StAR expression in endothelial cells, mouse brain microvascular endothelial cell line (bEnd.3) was treated with various steroids and oxysterols, including free cholesterol (CHO), low density lipoprotein (LDL), and 25-hydroxycholesterol (25-OH). All these three compounds increased StAR mRNA and protein expression in a time- and dose-dependent manner. When treated with CHO and LDL, the StAR mRNA change was prior to the protein change, suggesting that transcription may be one of the mechanisms of CHO and LDL regulation. In contrast to CHO and LDL, 25-OH increased StAR protein levels independently of mRNA amount. It suggested that 25-OH might regulate StAR activity at post-transcriptional level.

Animals↗
PubMed2006

Identification of a novel sulfonated oxysterol, 5-cholesten-3beta,25-diol 3-sulfonate, in hepatocyte nuclei and mitochondria.

This study reports the discovery of a novel sulfonated oxysterol found at high levels in the mitochondria and nuclei of primary rat hepatocytes after overexpression of the gene encoding steroidogenic acute regulatory protein (StarD1). Forty-eight hours after infection of primary rat hepatocytes with recombinant adenovirus encoding StarD1, rates of bile acid synthesis increased by 4-fold. Concurrently, [(14)C]cholesterol metabolites (oxysterols) were increased dramatically in both the mitochondria and nuclei of StarD1-overexpressing cells, but not in culture medium. A water-soluble [(14)C]oxysterol product was isolated and purified by chemical extraction and reverse-phase HPLC. Enzymatic digestion, HPLC, and tandem mass spectrometry analysis identified the water-soluble oxysterol as 5-cholesten-3beta,25-diol 3-sulfonate. Further experiments detected this cholesterol metabolite in the nuclei of normal human liver tissues. Based upon these observations, we hypothesized a new pathway by which cholesterol is metabolized in the mitochondrion.

Animals↗
PubMed2002

[To identify human and sheep placentas by FT-IR and RP-HPLC techniques].

Placenta has a long history of being Chinese traditional medicine. The quality control methods used nowadays in the markets were mainly based on the amino acid content of the placenta. However, it is hard to distinguish human placenta from sheep placenta with these methods. In this paper, a novel method was established employing FT-IR and RP-HPLC techniques. This method can distinguish human placenta from sheep placenta and may help to improve quality control of placenta in the markets.

Amino Acids↗
PubMedDate not supplied

Nanovesicular vaccines: exosomes.

Exosomes are small membrane vesicles derived from late endosome. They are about 30--100 nm in diameter. The secretion of exosomes is a process in which multivesicular bodies fuse with the cell membrane, and all cells that contain multivesicular endocytic compartments could theoretically secrete exosomes. The surprising biological functions of exosomes are only slowly being unveiled, but it is already clear that they serve to remove obsolete membrane proteins and act as messages of inter-cellular communication. Exosomes derived from tumor or antigen-presenting cells have been extensively investigated. They are released into the extracellular environment and fuse with the membranes of neighboring cells, delivering membrane and cytoplasmic proteins from one cell to another. Exosomes carry immunorelevant structures which play important roles in immune response, such as MHC molecules, costimulatory molecules, heat shock proteins, and naive tumor antigens. Therefore they have been suggested as potential vaccines. Consequently, exosomes have shown considerable anti-tumor effect in several studies and are in phase I clinical trials.

Animals↗