Biomedical subjects

Xiaowei Lu

Publications and source records attributed to Xiaowei Lu.

9 recordsLinked to original sources

PubMed2026

Efficacy of endometrial microbiota testing-guided personalized therapy in infertile women stratified by CD138 status: a retrospective cohort study.

BACKGROUND: Chronic endometritis (CE) is a persistent inflammatory condition of the endometrium associated with infertility. Current diagnosis relies on histopathological markers like CD138, which may not fully assess the functional state of the endometrial microenvironment. This study aimed to investigate whether the endometrial microbiome test (EMT) combined with personalized therapy could improve pregnancy outcomes in infertile women undergoing IVF, compared with standard management based on CD138 results. METHODS: This retrospective cohort study included 336 infertile women (aged 22-37 years) who underwent the CD138 test in Xiangtan Central Hospital between January 2020 and December 2022. Among them, 162 patients opted to undergo concurrent EMT using 16S rRNA sequencing and received EMT-guided personalized treatment. After excluding patients with missing CD138 results, those who underwent sequential embryo transfer, and those with endometrial thickness <7 mm at the time of transfer, 151 patients were included in the EMT group and 155 in the non-EMT group. The non-EMT group received standard management based on CD138 results (empirical antibiotics for CD138-positive patients; no treatment for CD138-negative patients). Clinical outcomes were compared between the two groups overall and after stratification by CD138 status. Multivariable logistic regression was performed to adjust for confounders. RESULTS: The overall live birth rate in the EMT group was 64.24% (97/151), which was higher than the non-EMT group (46.45%, 72/155, adjusted p=0.004). Among CD138-negative patients, EMT-guided therapy was associated with a significantly higher clinical pregnancy rate (70.89% vs. 53.41%, adjusted p=0.011), ongoing pregnancy rate (62.03% vs 46.59%, adjusted p=0.041), and live birth rate (60.76% vs. 43.18%, adjusted p=0.030) compared to no treatment. Among CD138-positive patients, EMT-guided therapy showed no significant improvement for the ongoing pregnancy rate (69.44% vs. 52.24%, adjusted p=0.142) or the live birth rate (68.06% vs. 50.75%, adjusted p=0.118) compared to empirical antibiotic treatment. CONCLUSION: EMT-guided personalized therapy was associated with favorable reproductive outcomes in CD138-negative women with infertility, identifying a subgroup that may benefit from microbiota-targeted intervention. For CD138-positive patients, the added value of EMT over empirical antibiotic therapy remains uncertain and warrants further investigation. EMT may guide treatment in CD138-negative cases via sequential diagnosis, though prospective validation is needed.

Humans↗

PubMed2006

Some C. elegans class B synthetic multivulva proteins encode a conserved LIN-35 Rb-containing complex distinct from a NuRD-like complex.

The Caenorhabditis elegans synthetic multivulva (synMuv) genes act redundantly to antagonize the specification of vulval cell fates, which are promoted by an RTK/Ras pathway. At least 26 synMuv genes have been genetically identified, several of which encode proteins with homologs that act in chromatin remodeling or transcriptional repression. Here we report the molecular characterization of two synMuv genes, lin-37 and lin-54. We show that lin-37 and lin-54 encode proteins in a complex with at least seven synMuv proteins, including LIN-35, the only C. elegans homolog of the mammalian tumor suppressor Rb. Biochemical analyses of mutants suggest that LIN-9, LIN-53, and LIN-54 are required for the stable formation of this complex. This complex is distinct from a second complex of synMuv proteins with a composition similar to that of the mammalian Nucleosome Remodeling and Deacetylase complex. The class B synMuv complex we identified is evolutionarily conserved and likely functions in transcriptional repression and developmental regulation.

Animals↗

PubMed2006

UNC5A promotes neuronal apoptosis during spinal cord development independent of netrin-1.

In addition to their role as chemorepellent netrin-1 receptors, UNC5 proteins may mediate cell death because they induce apoptosis in cultured cells. To test this in vivo, we generated Unc5a (formerly Unc5h1) knockout mice and found that this deletion decreased apoptosis and increased the number of neurons in the spinal cord. In contrast, loss of netrin-1 (Ntn1) did not affect the amount of apoptosis, suggesting that NTN1 is not required for neuronal apoptosis in vivo.

Animals↗

PubMed2006

C. elegans ISWI and NURF301 antagonize an Rb-like pathway in the determination of multiple cell fates.

The class A, B and C synthetic multivulva (synMuv) genes act redundantly to negatively regulate the expression of vulval cell fates in Caenorhabditis elegans. The class B and C synMuv proteins include homologs of proteins that modulate chromatin and influence transcription in other organisms similar to members of the Myb-MuvB/dREAM, NuRD and Tip60/NuA4 complexes. To determine how these chromatin-remodeling activities negatively regulate the vulval cell-fate decision, we isolated a suppressor of the synMuv phenotype and found that the suppressor gene encodes the C. elegans homolog of Drosophila melanogaster ISWI. The C. elegans ISW-1 protein likely acts as part of a Nucleosome Remodeling Factor (NURF) complex with NURF-1, a nematode ortholog of NURF301, to promote the synMuv phenotype. isw-1 and nurf-1 mutations suppress both the synMuv phenotype and the multivulva phenotype caused by overactivation of the Ras pathway. Our data suggest that a NURF-like complex promotes the expression of vulval cell fates by antagonizing the transcriptional and chromatin-remodeling activities of complexes similar to Myb-MuvB/dREAM, NuRD and Tip60/NuA4. Because the phenotypes caused by a null mutation in the tumor-suppressor and class B synMuv gene lin-35 Rb and a gain-of-function mutation in let-60 Ras are suppressed by reduction of isw-1 function, NURF complex proteins might be effective targets for cancer therapy.

Adenosine Triphosphatases↗

PubMed2006

Absorption and metabolism of Astragali radix decoction: in silico, in vitro, and a case study in vivo.

To profile absorption of Astragali Radix decoction and identify its orally absorbable constituents and their metabolites, four complementary in silico, in vitro, and in vivo methods, i.e., a computational chemistry prediction method, a Caco-2 cell monolayer model experiment, an improved rat everted gut sac experiment, and a healthy human volunteer experiment, were used. According to the in silico computation result, 26 compounds of Astragali Radix could be regarded as orally available compounds, including 12 flavonoids. In the in vitro and in vivo experiments, 21 compounds were tentatively identified by high-performance liquid chromatography-diode array detection-electrospray ion trap tandem mass spectrometry data, which involved calycosin, formononetin, (6aR,11aR)-3-hydroxy-9,10-dimethoxypterocarpan, 7,2'-dihydroxy-3',4'-dimethoxyisoflavan, calycosin-7-O-beta-D-glucoside, formononetin-7-O-beta-D-glucoside, 7,2'-dihydroxy-3',4'-dimethoxyisoflavan-7-O-beta-D-glucoside-6''-O-malonate, (6aR,11aR)-3-hydroxy-9,10-dimethoxypterocarpan-3-O-beta-D-glucoside, and phase II metabolites calycosin-7-O-beta-D-glucuronide, formononetin-7-O-beta-D-glucuronide, (6aR,11aR)-3-hydroxy-9,10-dimethoxypterocarpan-3-O-beta-D-glucuronide, 7,2'-dihydroxy-3',4'-dimethoxyisoflavan-7-O-beta-D-glucuronide, and calycosin sulfate. Calycosin and formononetin were proved absorbable by four methods; (6aR,11aR)-3-hydroxy-9,10-dimethoxypterocarpan and 7,2'-dihydroxy-3',4'-dimethoxyisoflavan were proved absorbable by three methods; formononetin-7-O-beta-D-glucoside and (6aR,11aR)-3-hydroxy-9,10-dimethoxypterocarpan-3-O-beta-D-glucoside were proved absorbable by two methods. The existence of calycosin-7-O-beta-D-glucuronide, formononetin-7-O-beta-D-glucuronide, (6aR,11aR)-3-hydroxy-9,10-dimethoxypterocarpan-3-O-beta-D-glucuronide, 7,2'-dihydroxy-3',4'-dimethoxyisoflavan-7-O-beta-D-glucuronide, and calycosin sulfate was proved by two or three methods. We found that besides isoflavones, pterocarpans and isoflavans also could be metabolized by the intestine during absorption, and the major metabolites were glucuronides. In conclusion, the present study demonstrated that the flavonoids in Astragali Radix decoction, including isoflavones, pterocarpans, and isoflavans, could be absorbed and metabolized by the intestine. These absorbable compounds, which were reported to have various bioactivities related to the curative effects of Astragali Radix decoction, could be regarded as an important component of the effective constituents of Astragali Radix decoction.

Adult↗

PubMed2005

Gene targeting using a promoterless gene trap vector ("targeted trapping") is an efficient method to mutate a large fraction of genes.

A powerful tool for postgenomic analysis of mammalian gene function is gene targeting in mouse ES cells. We report that homologous recombination using a promoterless gene trap vector ("targeting trapping") yields targeting frequencies averaging above 50%, a significant increase compared with current approaches. These high frequencies appear to be due to the stringency of selection with promoterless constructs, because most random insertions are silent and eliminated by drug selection. The promoterless design requires that the targeted gene be expressed in ES cells at levels exceeding a certain threshold (which we estimate to be approximately 1% of the transferrin receptor gene expression level, for the secretory trap vector used here). Analysis of 127 genes that had been trapped by random (nontargeted) gene trapping with the same vector shows that virtually all are expressed in ES cells above this threshold, suggesting that targeted and random trapping share similar requirements for expression levels. In a random sampling of 130 genes encoding secretory proteins, about half were expressed above threshold, suggesting that about half of all secretory genes are accessible by either targeted or random gene trapping. The simplicity and high efficiency of the method facilitate systematic targeting of a large fraction of the genome by individual investigators and large-scale consortia alike.

Animals↗

PubMed2004

The netrin receptor UNC5B mediates guidance events controlling morphogenesis of the vascular system.

Blood vessels and nerves are complex, branched structures that share a high degree of anatomical similarity. Guidance of vessels and nerves has to be exquisitely regulated to ensure proper wiring of both systems. Several regulators of axon guidance have been identified and some of these are also expressed in endothelial cells; however, the extent to which their guidance functions are conserved in the vascular system is still incompletely understood. We show here that the repulsive netrin receptor UNC5B is expressed by endothelial tip cells of the vascular system. Disruption of the Unc5b gene in mice, or of Unc5b or netrin-1a in zebrafish, leads to aberrant extension of endothelial tip cell filopodia, excessive vessel branching and abnormal navigation. Netrin-1 causes endothelial filopodial retraction, but only when UNC5B is present. Thus, UNC5B functions as a repulsive netrin receptor in endothelial cells controlling morphogenesis of the vascular system.

Animals↗

PubMed2004

PTK7/CCK-4 is a novel regulator of planar cell polarity in vertebrates.

In addition to the apical-basal polarity pathway operating in epithelial cells, a planar cell polarity (PCP) pathway establishes polarity within the plane of epithelial tissues and is conserved from Drosophila to mammals. In Drosophila, a 'core' group of PCP genes including frizzled (fz), flamingo/starry night, dishevelled (dsh), Van Gogh/strabismus and prickle, function to regulate wing hair, bristle and ommatidial polarity. In vertebrates, the PCP pathway regulates convergent extension movements and neural tube closure, as well as the orientation of stereociliary bundles of sensory hair cells in the inner ear. Here we show that a mutation in the mouse protein tyrosine kinase 7 (PTK7) gene, which encodes an evolutionarily conserved transmembrane protein with tyrosine kinase homology, disrupts neural tube closure and stereociliary bundle orientation, and shows genetic interactions with a mutation in the mouse Van Gogh homologue vangl2. We also show that PTK7 is dynamically localized during hair cell polarization, and that the Xenopus homologue of PTK7 is required for neural convergent extension and neural tube closure. These results identify PTK7 as a novel regulator of PCP in vertebrates.

Animals↗

PubMed2004

Identification of residues of the Caenorhabditis elegans LIN-1 ETS domain that are necessary for DNA binding and regulation of vulval cell fates.

LIN-1 is an ETS domain protein. A receptor tyrosine kinase/Ras/mitogen-activated protein kinase signaling pathway regulates LIN-1 in the P6.p cell to induce the primary vulval cell fate during Caenorhabditis elegans development. We identified 23 lin-1 loss-of-function mutations by conducting several genetic screens. We characterized the molecular lesions in these lin-1 alleles and in several previously identified lin-1 alleles. Nine missense mutations and 10 nonsense mutations were identified. All of these lin-1 missense mutations affect highly conserved residues in the ETS domain. These missense mutations can be arranged in an allelic series; the strongest mutations eliminate most or all lin-1 functions, and the weakest mutation partially reduces lin-1 function. An electrophoretic mobility shift assay was used to demonstrate that purified LIN-1 protein has sequence-specific DNA-binding activity that required the core sequence GGAA. LIN-1 mutant proteins containing the missense substitutions had dramatically reduced DNA binding. These experiments identify eight highly conserved residues of the ETS domain that are necessary for DNA binding. The identification of multiple mutations that reduce the function of lin-1 as an inhibitor of the primary vulval cell fate and also reduce DNA binding suggest that DNA binding is essential for LIN-1 function in an animal.

Amino Acid Sequence↗