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Biomedical subjects

Li Deng

Publications and source records attributed to Li Deng.

At least 19 recordsLinked to original sources
PubMed2026

A Phase I Study Assessing the Safety, Tolerability, and Pharmacokinetics of Yinfenidone: A Novel, Potent Drug for Idiopathic Pulmonary Fibrosis Treatment in Healthy Chinese Subjects.

PURPOSE: Idiopathic pulmonary fibrosis (IPF) is a fatal interstitial lung disease with a median survival of only 2-3 years after diagnosis. Yinfenidone (HEC585) possesses the potential to inhibit the proliferation of pulmonary fibroblasts, making it a promising candidate for the treatment of IPF. This study assessed the safety, tolerability, pharmacokinetics, and metabolic profile of Yinfenidone hydrochloride capsule in healthy Chinese subjects. METHODS: This single-center, randomized, double-blind, placebo-controlled, single ascending-dose trial included seven dose groups(20, 50, 100, 200, 400, 600, and 800 mg). Each group enrolled8 healthy subjects: 6 received Yinfenidone hydrochloride capsules and 2 received matching placebo under fasting conditions. Serial pharmacokinetic (PK) blood samples were collected pre-dose and post-dose, liquid chromatography-tandem mass spectrometry was used to analyze the plasma concentrations of Yinfenidone. Additionally, metabolic biotransformation of Yinfenidone in plasma were conducted in the 100 mg dose group. Safety and tolerability endpoints were monitored via physical examinations, vital signs measurements, clinical laboratory tests, 12-lead electrocardiography (ECG), and adverse events (AEs) documentation throughout the trial. FINDINGS: Yinfenidone was rapidly absorbed, with a median maximum plasma concentration (Tmax) of 1.8-3.0 hours, and had a mean half-life (t1/2) ranging from 31.9 to 62.0 hours. Within the 20-100 mg dose range, systemic drug exposure generally increased with ascending dose, above 100 mg, exposure increased less than proportionally to dose. Metabolite profiling in the 100 mg group revealed that the parentcompound predominated in plasma, with metabolic pathways including mono-oxygenation and N-dealkylation. All reported AEswere mild, classified as Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 grade 1. No serious AEs observed; no subject discontinued the trial due to AEs. Single oral doses of 20-800 mg Yinfenidone hydrochloride capsules administered under fasting conditions demonstrated favorable safety and tolerability profiles in healthy Chinese subjects. IMPLICATIONS: Yinfenidone exhibited rapid absorption (median Tmax, 1.8-3.0 hours) and a long terminal t1/2 ranging from 31.9 to 62.0 hours in this single ascending-dose study, indicating that Yinfenidone can be taken once a day in subsequent clinical studies. Yinfenidone mainly exists in human plasma as the original drug and is metabolized through a variety of metabolic pathways. The AEs observed with Yinfenidone in this study, such as diarrhea, nausea, and dizziness, were similar to those reported with pirfenidone. Overall, Yinfenidone demonstrated a favorable safety and tolerability profile in this cohort of healthy subjects.

Adult↗
PubMed2026

Bacteria and phage consortia modulate cecal SCFA production and host metabolism to enhance feed efficiency in ducks.

BACKGROUND: The gut microbiota influences poultry health, nutrition, feed efficiency (FE), and overall productivity. However, the relationship between gut microbes, including bacteria and phages, and FE in ducks remains underexplored. To address this, we integrated cecal 16S amplicon, metagenome, microbiota-derived short-chain fatty acids (SCFAs) profiling, liver transcriptome, and serum metabolome data to illustrate the contribution of the gut microbiome (bacteria and viruses) to duck FE. RESULTS: We reconstructed viral genomes and prokaryotic metagenome-assembled genomes (MAGs) and annotated their genes using comprehensive databases. Prokaryotic hosts of viruses were also predicted to understand virus-host dynamics within the gut ecosystem. Our results revealed that high-FE ducks have higher concentration of propionate and butyrate in cecum compared with low-FE ducks. The metagenome sequencing revealed distinct cecal microbiota profiles between two groups, with increased relative abundance of representative SCFA producers, especially Paraprevotella sp905215575 and Bacteroides sp944322345, and enhanced SCFA-biosynthesis pathways in high-FE ducks. Virome genome assembly identified two phages encoding auxiliary metabolic genes (AMGs) involved in pyruvate metabolism, enhancing nutrient availability for host bacteria to produce SCFAs (e.g., temperate phage-encoded pyruvate phosphate dikinase) or exploiting host central metabolic pathways for viral replication (e.g., lytic phage-encoded formate C-acetyltransferase). Furthermore, these representative SCFA-producing bacteria and phage consortia were associated with serum metabolites (including L-histidine and 4-hydroxydecanedioylcarnitine) linked to duck FE. CONCLUSION: Collectively, these findings provide novel insights into the gut microbial factors regulating FE in ducks, offering potential strategies to optimize poultry nutrition and productivity. Video Abstract.

Animals↗
PubMed2025

Integrated data mining and network pharmacology to explore the prescription patterns from a senior TCM oncologist's clinical practice in treating chemotherapy-induced hand-foot syndrome.

Hand-foot syndrome (HFS) is a common and refractory adverse effect of chemotherapy lacking specific therapeutic strategies currently. Traditional Chinese medicine (TCM) has shown empirical efficacy in clinical HFS management. This study integrated data mining and network pharmacology to systematically elucidate the medication principles and molecular mechanisms underlying Professor Gang Xie's prescriptions for HFS. All medical records from Professor Xie's specialist clinic (January 2020 to March 2025) were retrospectively collected and standardized in Excel. Prescriptions were analyzed through frequency statistics, association and clustering. Active ingredients of core herb pairs and their disease-related targets were identified using TCMSP, HERB, GeneCards, PharmGKB and GEO databases. Protein-protein interaction (PPI) networks, gene ontology (GO), and Kyoto encyclopedia of genes and genomes (KEGG) pathway analyses were performed. Molecular docking validated interactions between key bioactive compounds and targets. This study involved 217 prescriptions containing 150 herbs. Core herb combinations comprised Radix Astragali (Huangqi), Poria (Fuling), and Radix Pseudostellariae (Taizishen), predominantly classified as spleen-tonifying agents with warm properties, targeting lung, spleen, and stomach meridians. Network analysis identified 67 bioactive compounds and 899 disease targets. Quercetin, kaempferol, acacetin and luteolin were identified the key ingredients. The core targets (TP53, STAT3, PIK3CA, HSP90AA1, AKT1, CTNNB1, PI3KR1, MAPK1) were enriched in MAPK and PI3K-Akt signaling pathways. Molecular docking confirmed strong binding affinity between key compounds and targets. Professor Xie's therapeutic strategy for HFS emphasizes "spleen fortification, phlegm elimination, and stasis resolution." The core herb combination likely exerts anti-HFS effects via modulation of MAPK and PI3K-Akt pathways, providing a pharmacological basis for TCM-driven HFS management.

Network Pharmacology↗
PubMed2006

The breast cancer susceptibility allele CHEK2*1100delC promotes genomic instability in a knock-in mouse model.

Allelic variants of CHEK2 contribute to an elevated risk for human breast cancer and possibly other cancer types. In particular, the CHEK2*1100delC polymorphic variant has been identified as a low-penetrance breast cancer susceptibility allele in breast cancer families with wild type BRCA1 and BRCA2. To better understand the molecular basis by which this allele increases risk for disease, we have generated a mouse in which the wild type CHEK2 (Chk2 in mouse) allele has been replaced with the 1100delC variant. Mouse embryo fibroblasts (MEFs) derived from these mice have an altered cell cycle profile in which a far greater proportion of cells are in S-phase and in G2 (4N) compared with wild type cells. The mutant cells show signs of spontaneous genomic instability as indicated by polyploidy and an increase in DNA double strand breaks.

Alleles↗
PubMed2006

Enantioselective Friedel-Crafts reaction of indoles with carbonyl compounds catalyzed by bifunctional cinchona alkaloids.

In this communication, we report an efficient asymmetric Friedel-Crafts reaction that, unprecedently, is applicable to a wide range of both indoles and carbonyls. The use of a readily accessible catalyst in combination with a high enantioselectivity that is insensitive to reaction concentration, temperature, air, and moisture should allow this reaction to provide useful enantioselective access to new chiral indole derivatives. [reaction: see text]

Catalysis↗
PubMed2006

Gradient high-performance liquid chromatography for the simultaneous determination of chlorogenic acid and baicalin in plasma and its application in the study of pharmacokinetics in rats.

A novel HPLC-UV method was developed for the simultaneous determination of two major active components in Yinhuang injection, chlorogenic acid and baicalin, in rat plasma. Extracted from the plasma samples with methanol-acetonitrile (3:1, v/v), the two compounds were successfully separated using a C18 column with a gradient elution composed of 15 and 54% methanol-acetonitrile (1:1, v/v) in 0.2% (v/v) phosphoric acid water solution (pH 2.0). The flow-rate was set at 1 ml min(-1) and the eluent was detected at 327 nm for chlorogenic acid, 278 nm for baicalin. Puerarin and rutin were used as the internal standards for chlorogenic acid and baicalin, respectively. The method was linear over the range of 0.388-12.4 microg ml(-1), 0.485-124 microg ml(-1) for chlorogenic acid and baicalin, respectively. The correlation coefficient for each analyte was above 0.998. The intra-day and inter-day precisions were better than 7 and 9%, with the relative error ranging from -9.5 to 7.3% and from -4.2 to 1.8%. The limit of detection (LOD) and the limit of quantification (LOQ) for chlorogenic acid and baicalin in plasma were 0.194, 0.122, 0.388 and 0.485 microg ml(-1), respectively. This assay has been successfully applied in the pharmacokinetic study of chlorogenic acid and baicalin in vivo through intravenous administration of Yinhuang injection to rats.

Animals↗
PubMed2006

Asymmetric Friedel-crafts reaction of indoles with imines by an organic catalyst.

In this communication, we report an asymmetric Friedel-Crafts reaction of indoles with imines catalyzed by a bifunctional cinchona alkaloid catalyst. This is the first efficient organocatalytic asymmetric Friedel-Crafts reaction of indoles with imines. This reaction is operationally simple and, unprecedentedly, affords high enantioselectivity for a wide range of indoles and both aryl and alkyl imines. This establishes a direct, convergent, and versatile approach to optically active 3-indolyl methanamines, a structural motif embedded in numerous indole alkaloids and synthetic indole derivatives.

Catalysis↗
PubMed2006

The Mannich reaction of malonates with simple imines catalyzed by bifunctional cinchona alkaloids: enantioselective synthesis of beta-amino acids.

We describe the first efficient, direct asymmetric Mannich reactions with malonates and N-Boc aryl and alkyl imines by cooperative hydrogen-bonding catalysis with a cinchona alkaloid bearing a thiourea functionality. We have also extended the scope of this reaction to beta-ketoesters. The synthetic value of this new reaction is demonstrated in the establishment of a convergent enantioselective route toward the biologically important beta-amino acids under mild and air- and moisture-tolerant conditions.

Amino Acids↗
PubMed2006

Activation of IKK by TNFalpha requires site-specific ubiquitination of RIP1 and polyubiquitin binding by NEMO.

The receptor interacting protein kinase 1 (RIP1) is essential for the activation of nuclear factor kappaB (NF-kappaB) by tumor necrosis factor alpha (TNFalpha). Here, we present evidence that TNFalpha induces the polyubiquitination of RIP1 at Lys-377 and that this polyubiquitination is required for the activation of IkappaB kinase (IKK) and NF-kappaB. A point mutation of RIP1 at Lys-377 (K377R) abolishes its polyubiquitination as well as its ability to restore IKK activation in a RIP1-deficient cell line. The K377R mutation of RIP1 also prevents the recruitment of TAK1 and IKK complexes to TNF receptor. Interestingly, polyubiquitinated RIP1 recruits IKK through the binding between the polyubiquitin chains and NEMO, a regulatory subunit of the IKK complex. Mutations of NEMO that disrupt its polyubiquitin binding also abolish IKK activation. These results reveal the biochemical mechanism underlying the essential signaling function of NEMO and provide direct evidence that signal-induced site-specific ubiquitination of RIP1 is required for IKK activation.

Amino Acid Sequence↗
PubMed2006

Dual-function cinchona alkaloid catalysis: catalytic asymmetric tandem conjugate addition-protonation for the direct creation of nonadjacent stereocenters.

Catalytic tandem asymmetric reactions constitute a powerful strategy for the asymmetric construction of nonadjacent stereocenters in acyclic molecules directly from achiral precursors. In this Communication, we report a highly enantioselective and diastereoselective addition of trisubstituted carbon donors to 2-chloroacrylonitrile catalyzed by bifunctional cinchona alkaloid catalysts. This represents the first asymmetric tandem conjugate addition-protonation with efficient catalytic control of two nonadjacent stereocenters. As demonstrated in a concise and highly stereoselective formal total synthesis of (-)-manzacidin A, this asymmetric tandem reaction establishes a new and versatile catalytic approach for the enantioselective and diastereoselective creation of 1,3-tertiary-quaternary stereocenters.

Acrylonitrile↗
PubMed2006

Enantioselective nitroaldol reaction of alpha-ketoesters catalyzed by cinchona alkaloids.

The development of highly enantioselective and general catalytic nitroaldol (Henry) reactions with ketones is a challenging yet desirable task in organic synthesis. In this communication, we report an asymmetric nitroaldol reaction with alpha-ketoesters catalyzed by a new C6'-OH cinchona alkaloid catalyst. This is the first highly efficient organocatalytic asymmetric Henry reaction with ketones. This reaction is operationally simple and affords high enantioselectivity as well as good to excellent yield for a broad range of alpha-ketoesters.

Aldehydes↗
PubMed2006

Reproducibility of ultrasound pachymetry using the Sonogage Corneo-Gage Plus 2.

PURPOSE: The aim of this study was to determine the reproducibility of measurements made using the Sonogage Corneo-Gage Plus 2 (Cleveland, Ohio) ultrasound pachymeter of total corneal and corneal epithelial thickness in 5 different regions of the cornea. METHODS: Twenty-seven subjects at the New England College of Optometry (NECO) and 20 subjects at the Southern College of Optometry (SCO) were enrolled in this study. Measurements were taken of the central cornea as well as the nasal and temporal regions of the midperipheral and peripheral regions of the right cornea of each subject. Identical measurements were again taken in these subjects 1 week later at approximately the same time of day. Within-subject variations were then assessed using paired t tests. RESULTS: The only significant measurement differences that were found between visits were for full corneal thickness at both the nasal and temporal midperipheral locations. The mean differences for these locations were 13.5 microm and 13.7 microm, respectively. CONCLUSIONS: Epithelial corneal thickness and central and peripheral total corneal thickness measurements using the Corneo-Gage Plus 2 pachymeter were reproducible; however, midperipheral total corneal thickness measurements showed poor reproducibility.

Cornea↗
PubMed2006

Fabrication and detection of tissue-engineered bones with bio-derived scaffolds in a rotating bioreactor.

In order to explore the methods for commercialized bone tissue engineering, engineered bones should be cultivated in bioreactors to realize three-dimensional culture under well-defined culture conditions. In the present paper, osteoblasts isolated from the cranium of 1-month-old Zelanian rabbits were inoculated on to the BDBS (bio-derived bone scaffolds) to investigate the three-dimensional fabrication of engineered bone in an RWVB (rotating-wall vessel bioreactor). The osteoblasts, after being transfected with green fluorescent protein, were respectively seeded at 2 x 10(6) and 1 x 10(6) cells x ml(-1) on to the BDBS and then cultured in a T-flask and an RWVB for 1 week. The morphologies and structure of the fabricated bone were investigated by using an inverted microscope, a scanning electron microscope and a laser confocal microscope using the stains haematoxylin/eosin and Toluidine Blue. After being digested from the scaffolds, the cells were assayed with ALP (alkaline phosphatase) stain, von-Kossa staining on mineralized nodules, type I collagen and bone morphogenetic protein-2 expression, and the cell expansion and growth curves using different culture methods were quantitatively determined with MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide). Furthermore, cell cycle and apoptosis were detected by using a flow cytometer, and total DNA was also assayed. For a comparative study, cell-seeded constructs were also cultured under static conditions. The results show that the cell number cultured in the RWVB was five times that in the T-flask. Bone tissues cultured in the RWVB with two different densities grew well, and the osteoblasts maintained their normal cycle and DNA content. The result demonstrates that, with the stress stimulation in the fluid in the RWVB, the active expression of ALP can be increased, rapid proliferation and differentiation of osteoblasts are possible and the three-dimensional fabrication of engineered bone could be realized.

Animals↗
PubMed2006

[Basic study on the development of amniotic membrane and its application].

OBJECTIVE: To review the latest development of amniotic membrane and its application. METHODS: Related literatures on the development of amniotic membrane and its application were extensively reviewed and summarized. RESULTS: There were amniotic epithelial cells and many growth factors in the outer layer of amniotic membrane and there were many kinds of collagen in the basement. The special structure promoted the growth of many kinds of cells. It was widely used in ophthalmology. CONCLUSION: As it is easily available, compatible, cheap in price, low in antigenicity, and able to promote the growth of many kinds of cells, with few ethical problems involved, amniotic membrane will be more and more widely applied.

Amnion↗
PubMed2006

[Surveillance of antimicrobial susceptibility of Streptococcus pneumoniae and Hemophilus influenzae isolated from children in Guangzhou area between 2003 and 2004].

OBJECTIVE: To investigate the situation of antibiotic resistance of Streptococcus pneumoniae (Sp) and Hemophilus influenzae (Hi) clinical isolates from children in Guangzhou area. METHODS: The authors cultured, isolated and identified the Sp and Hi strains from nasopharyngeal secretion of patients who visited Guangzhou Children's Hospital for upper respiratory tract infection between 2003 and 2004. K-B disc diffusion and E-test for antibiotic susceptibility were performed for these clinical isolates. RESULTS: Totally 172 and 484 strains of Sp and Hi were respectively isolated from nasopharyngeal secretions in the hospital. For Sp strains, the rates of resistance to penicillin, amoxicillin/clavulanic acid, ceftriaxone, cefuroxime, cefaclor, erythromycin, tetracycline, chloramphenicol, sulfamethoxazole/trimethoprim (SMZ/TMP), clindamycin and ofloxacin were 32.0%, 11.1%, 32.6%, 18.1%, 39.5%, 82.6%, 78.5%, 24.4%, 87.2%, 69.2% and 3.1%, respectively. The penicillin non-susceptible Sp (PNSSP) isolates showed higher rates of resistance to other antimicrobial agents such as other beta-lactam antimicrobial agents, erythromycin, and SMZ/TMP than those of penicillin susceptible Sp (PSSP) isolates. More than 90% of PNSSP were multidrug resistant strains. The average rate of beta-lactamase production among 484 strains of Hi was 29.5% (143/484). For Hi isolates, the rates of resistance to ampicillin, amoxicillin/clavulanic acid, ceftriaxone, cefuroxime, cefaclor, SMZ/TMP, tetracycline, chloramphenicol, azithromycin, and ofloxacin were 40.1%, 3.4%, 4.1%, 1.9%, 5.6%, 56.2%, 52.1%, 17.4%, 2.1%, and 0.6%, respectively. CONCLUSION: The antimicrobials resistant Sp and Hi isolated from children with respiratory tract infection in the area have become a severe problem. The rate of resistance to penicillin of Sp had been decreased compared with the last three years, but the rate of resistance to ceftriaxone of Sp increased, and the multidrug resistance rates of PNSSP was rather high. PNSSP was characterized by a multidrug-resistance to erythromycin, tetracycline and SMZ/TMP. beta-lactamase production and ampicillin resistance among the Hi isolates from children in the area had increased generally during the period 2003 - 2004. The Hi isolates were more susceptible to the second and the third generation cephalosporins, amoxicillin/clavulanic acid and azithromycin.

Anti-Bacterial Agents↗
PubMed2006

[Effects of salbutamo and ipraopium bromide inhalation on pulmonary function in young children with asthmatoid bronchitis].

OBJECTIVE: The efficacy of bronchodilator in asthmatoid bronchitis remains controversial. This study was designed to investigate the effects of bronchodilators, salbutamo and ipraopium bromide, on the pulmonary function in young children with this disease. METHODS: Pulmonary function tests were performed in 20 children with asthmatoid bronchitis (2 months-2.5 years of age) before and 30, 60, and 120 minutes after salbutamo and ipratropium bromide inhalation. The indexes of pulmonary function measured included tidal breathing flow volume (TBFV) loop, percent of tidal volume to peak tidal expiratory flow (%V-PF), terminal flows per peak expiratory flow (25/PF), peak tidal expiratory flow (PTEF), rate of mid-expiratory to mid-inspiratory flow (ME/MI), respiratory rate (RR) and tidal volume per kilogram (TV/kg). RESULTS: Before drug inhalation, the descending branch of the TBFV loop was depressed. The PTEF shifted forward and %V-PF (0.19 +/- 0.04) and 25/PF (0.42 +/- 0.11) decreased. These changes did not improve and the remaining indexes, RR, ME/MI and TV/kg, 30, 60, and 120 minutes after drug inhalation also remained similar to before inhalation. CONCLUSIONS: Salbutamo and ipratropium bromide inhalation did not improve the airway resistance and ventilation function in children with asthmatoid bronchitis. This suggests that the efficacy of bronchodilator in the treatment of this disease is doubtful.

Administration, Inhalation↗