Biomedical subjects

Xiaowei Hu

Publications and source records attributed to Xiaowei Hu.

5 recordsLinked to original sources

PubMed2026

Multi-trait polygenic scores for COPD and COPD exacerbations implicate druggable proteins.

BACKGROUNDWe constructed multi-trait polygenic risk scores (PRSs) predicting chronic obstructive pulmonary disease (COPD) and exacerbations, validated their performance in diverse cohorts, and identified PRS-related proteins for potential therapeutic targeting.METHODSPRSmix+, a multi-trait PRS framework, is used to train a composite PRS (PRSmulti) in COPDGene non-Hispanic White participants (n = 6,647). Associations of PRSmulti with COPD status (GOLD 2-4 vs. GOLD 0 or ICD) and exacerbation frequency were tested in COPDGene African American (n = 2,466), ECLIPSE (n = 1,858), Mass General Brigham Biobank (n = 15,152), and All of Us (n = 118,566). Protein prediction models were applied to GWAS summary statistics from traits contributing to PRSmulti and were validated with proteomic data in COPDGene (n = 5,173) and UK Biobank (n = 5,012).RESULTSPRSmix+ selected 7 traits for PRSmulti. In multivariable models, PRSmulti was associated with COPD status (meta-analysis random effects [RE] OR 1.58 [95% CI: 1.28-1.94]) and exacerbation frequency (meta-analysis RE β 0.21 [95% CI: 0.11-0.31]), with higher effect sizes observed in smoking-enriched cohorts. PRSmulti outperformed traditional single-trait PRS in all tested cohorts. Using protein prediction models, we identified 73 proteins associated with the PRSs that were also validated with measured protein levels in COPDGene and UK Biobank. Of these proteins, 25 were linked to approved or investigational drugs. Notable targets include RAGE/sRAGE, IL1RL1, and SCARF2, all implicated in COPD pathogenesis and exacerbations.CONCLUSIONSMulti-trait PRS improves prediction of COPD and exacerbation risk. Integration with proteomic data identifies druggable protein targets, offering a promising avenue for precision medicine in COPD management.TRIAL REGISTRATIONCOPDGene: ClinicalTrials.gov NCT00608764; ECLIPSE: ClinicalTrials.gov NCT00292552.

Humans↗

PubMed2023

Genetic variants in the complement system and their potential link in the aetiology of type 1 diabetes.

Type 1 diabetes is an autoimmune disease in which one's own immune system destroys insulin-secreting beta cells in the pancreas. This process results in life-long dependence on exogenous insulin for survival. Both genetic and environmental factors play a role in disease initiation, progression, and ultimate clinical diagnosis of type 1 diabetes. This review will provide background on the natural history of type 1 diabetes and the role of genetic factors involved in the complement system, as several recent studies have identified changes in levels of these proteins as the disease evolves from pre-clinical through to clinically apparent disease.

Humans↗

PubMed2006

Inhaled nitric oxide attenuates hyperoxic and inflammatory injury without alteration of phosphatidylcholine synthesis in rat lungs.

We hypothesized that inhaled nitric oxide (iNO), a selective vasodilator for pulmonary hypertension, may exacerbate hyperoxia-related lung inflammatory injury by alteration of phosphatidylcholine (PC) synthesis in mature lungs. Healthy adult rats were allocated to 4 groups and exposed to: 95% oxygen, or 20ppm iNO, or both (ONO), or room air, all for 48h. (3)H-choline chloride was injected i.v. at 10min, 8, 16, and 24h prior to the end of 48h exposure and the animal lungs were processed. In oxygen group, oxidative damage and inflammation were significantly induced compared to the room air group. In ONO group there were significantly elevated glutathione, attenuated malondialdehyde, myeloperoxidase, and wet-to-dry lung weight ratio in lung parenchyma, decreased white cell counts and vascular-to-alveolar leakage of albumin in bronchoalveolar lavage fluid. In both oxygen and ONO groups both total phospholipids and surfactant protein-A were significantly increased compared with the room air group. Newly synthesized (3)H-PC was low in the lungs of NO group but high over time in both oxygen and ONO groups. Morphologically, lung injury was mild in ONO, but moderate in both oxygen and NO groups. We conclude that iNO alleviated oxidative damage and inflammation, and reduced alveolar leakage in hyperoxic injury of the mature lungs. Hyperoxia enhanced production of surfactant, whereas iNO did not attenuate this effect.

Administration, Inhalation↗

PubMed2004

Mitigation of meconium-induced lung injury by surfactant and inhaled nitric oxide is associated with suppression of nuclear transcription factor kappa B.

OBJECTIVE: To investigate whether the mechanism of a combined surfactant and inhaled nitric oxide (iNO) in improvement of oxygenation and mitigation of lung injury is associated with suppression of nuclear transcription factor kappa B (NF-kappaB) in the lung tissue of ventilated rabbits with meconium aspiration. METHODS: Adult rabbits (weight 2.0-3.5 kg, n = 33) were anesthetized, intratracheally received human meconium, and were subjected to pressure support ventilation for 30-60 min to induce hypoxemic respiratory failure and lung injury. They were then treated for 6 h in groups: control animals; rabbits receiving iNO; animals receiving surfactant (100 mg/kg), and rabbits receiving both iNO and surfactant. iNO was delivered continuously by mass flow controller in sequence at 1, 10, 20, and 40 ppm each for 60 min at 30-min intervals. RESULTS: Improvement in oxygenation and lung mechanics was found in the animals receiving both iNO and surfactant, associated with a marked response to iNO at 10 and 20 ppm (p < 0.05), a significantly higher ratio of disaturated phosphatidylcholine to total proteins, a lower surface tension of phospholipids from bronchoalveolar lavage fluid, a lower wet-to-dry lung weight ratio and lower lung injury scores, and better alveolar aeration. The iNO- and surfactant-treated groups had only transient or moderate-to-intermediate improvement in the associated parameters. The expression of NF-kappaB in lung tissue was enhanced in the control group, attenuated in the groups treated with either iNO or surfactant, and significantly suppressed in the group receiving both iNO and surfactant. CONCLUSION: Improvements of lung mechanics and gas exchange and mitigation of lung injury by the combined surfactant and iNO are related to suppression of NF-kappaB expression in lung tissue of ventilated rabbits with hypoxemic respiratory failure.

Animals↗

PubMed2004

[Identification of Fructus Schisandrae chinensis and Fructus Schisandrae sphenantherae in wu zi yan zong pill by RP-HPLC analysis].

OBJECTIVE: To identify Fructus schisandrae chinensis and Fructus schisandrae sphenantherae in wu zi yan zong pill (WZYZP). METHODS: Columm SUPELCOSIL C18; Mobile phase: methanol-water (65:35); Detection wavelength: 254 nm. RESULTS: Using above optimum chromatography conditions, the HPLC chromatography of relative medicinal materials and WZYZP was established. CONCLUSION: HPLC chromatography can be used for identification of Fructus schisandrae chinensis and Fructus schisandrae sphenantherae in WZYZP.

Chromatography, High Pressure Liquid↗