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Biomedical subjects

W C Liu

Publications and source records attributed to W C Liu.

At least 19 recordsLinked to original sources

[Laryngeal squamous cell carcinoma-derived exosomes promote neuronal axonal growth by remodeling the neural microenvironment].

Objective: Perineural invasion (PNI) is a critical determinant of poor prognosis in laryngeal squamous cell carcinoma (LSCC), but its underlying mechanisms remain unclear. This study aimed to investigate whether LSCC-derived exosomes induce axonal growth by delivering neuroactive molecules, thereby contributing to tumor perineural invasion. Methods: Clinical data from the laryngeal cancer cohort of The Cancer Genome Atlas Head and Neck Squamous Cell Carcinoma (TCGA-HNSC) dataset were analyzed. Propensity score matching (PSM) and Cox regression were used to evaluate the prognostic value of nerve density, and these findings were validated using 35 pairs of laryngeal cancer and adjacent normal tissue specimens collected at Yantai Yuhuangding Hospital between 2022 and 2026 to assess neural morphological changes. Exosomes were isolated from the human LSCC cell line AMC-HN-8, characterized by quality-control assays, and co-cultured with PC12 cells. A rescue experiment using GW4869, a specific inhibitor of neutral sphingomyelinase, was performed to confirm the exosome-dependent effect. Neurite outgrowth was evaluated by immunofluorescence, and the expression of axonal growth-related genes was measured by RT-qPCR. Targeted metabolomics was employed for the absolute quantification of neuroactive metabolites within the vesicles and for pathway enrichment analysis. Results: After PSM adjustment, high nerve density was identified as an independent poor prognostic factor in LSCC patients (HR=2.10, P=0.035), with particularly pronounced prognostic value in the early-stage node-negative (N0) subgroup (HR=4.07, P=0.001). Pathological sections showed high expression of the neural markers &#x3b2;III-tubulin and PGP9.5 in LSCC tissues (&#x3b2;III-tubulin: t=2.234, P<0.05; PGP9.5: t=2.575, P<0.05). Exosomes were successfully isolated from AMC-HN-8 cells and passed quality control. In vitro assays showed that LSCC-derived exosomes significantly promoted neurite extension and branching in PC12 cells (t=4.147, P<0.000 1) and upregulated core axonal growth genes, including GAP-43, NEFL, and NEFM (GAP-43: t=3.698, P<0.05; NEFL: t=5.113, P<0.01; NEFM: t=5.263, P<0.01); this effect was completely reversed by the exosome-release inhibitor GW4869 (t=3.535, P<0.001). Targeted metabolomics revealed a specific enrichment of 12 neurotransmitters and metabolites within LSCC exosomes, centered on glutamine (83.411 &#x3bc;mol/L, FC=1.88) and glutamate (18.461 &#x3bc;mol/L, FC=1.21), which were significantly enriched in signaling pathways such as "central carbon metabolism in cancer" and "glutamatergic synapse". Conclusion: Nerve density is a potential adverse prognostic factor in patients with LSCC. LSCC-derived exosomes can directly induce axonal growth in neuron-like cells, suggesting that tumor cells actively remodel the neural microenvironment and drive axonal growth through exosome-mediated long-range signaling.

Exosomes

The role of vasopressin on the effect of U-50,488 to block the development of morphine tolerance and physical dependence.

U-50,488, a selective kappa-opioid receptor agonist, has been reported to inhibit the development of antinociceptive tolerance to morphine in mice, rats and guinea pigs, but the mechanism involved in this action remains unknown. Since U-50,488 has been reported to suppress the plasma vasopressin level, we investigated the role of vasopressin with U-50,488 in the male Sprague Dawley rat in this study. Animals (230-270 g) were chronically treated with morphine (10 mg/kg, i.p.) twice a day for 6 days in order to induce tolerance to antinociceptive effect measured by tail-flick test. Withdrawal symptoms were precipitated by naloxone (10 mg/kg, i.p.) on day 7. U-50,488 (i.p.) or AVP (i.p. or i.c.v.) or U-50,488 and AVP was (were) coadministered with chronic morphine to investigate their effects on morphine tolerance and dependence. We found that coadministration of 8 mg/kg U-50,488 (i.p.) with morphine almost completely block morphine tolerance and partially block withdrawal symptoms. In contrast, coadministration of AVP (0.3 microgram/kg, i.p., or 0.01 microgram, i.c.v.) with morphine and U-50,488, the effects of U-50,488 to block morphine tolerance and dependence were reversed. In addition, treatment of AVP antagonist (dPTyr(Me)AVP, 0.5 microgram/kg, i.p. or 0.5 microgram, i.c.v.) has the similar effect as U-50,488 to block morphine tolerance. In summary, the effect of U-50,488 to block morphine tolerance and dependence may relate to its inhibitory effect on AVP release.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh

Percutaneous intratumoral injection of cisplatin microspheres in tumor-bearing rats to diminish acute nephrotoxicity.

Poly(D,L-lactide) microspheres loaded with cisplatin (PLA-CDDP MS) were prepared by a solvent evaporation technique for direct intratumoral injection. The microspheres, 50-100 microns, containing 40.04% of cisplatin produce sustained release in vitro. PLA-CDDP MS (6 mg/kg body weight of cisplatin) suspensions were injected intratumorally into mammary tumors in rats. Cisplatin solution (6 mg/kg body weight) was injected either intratumorally or intraperitoneally in two groups. After treatments, the tumor size decreased in each of the groups as a function of time. Sixteen days post-injection, the tumors had either disappeared or significantly shrunk. PLA-CDDP MS had a similar antitumor effect compared with cisplatin aqueous solution. Blood urea nitrogen, serum creatinine and histopathology examinations revealed that the renal toxicity in the PLA-CDDP MS group was significantly less than in the control groups. These results indicate that intratumoral injection of PLA-CDDP MS maintains anticancer potency and reduces acute renal toxicity.

Animals

[Studies on semi-synthesis of cephalotaxine esters and correlation of their structures with antitumor activity].

Ten esters of cephalotaxine with amino acids possessing widely different structural features have been synthesized and tested for antitumor activity. Preliminary data showed that compound 6 is the most active one. However, it is still less potent than harringtonine. Other synthetic esters possess varying activities at 10 micrograms/ml. Preliminary structure activity relationship of these esters was discussed.

Antineoplastic Agents, Phytogenic

10'-Desmethoxystreptonigrin, a novel analog of streptonigrin.

10'-Desmethoxystreptonigrin, a novel analog of streptonigrin produced by Streptomyces albus, was discovered in a screen for inhibitors of farnesylation of RAS p21 protein. The compound was isolated from the fermentation broth and its structure determined. It is markedly cytotoxic to several human tumor cell lines and also exhibits potent broad-spectrum antibacterial activity.

Animals

Aerocavin, a new antibiotic produced by Chromobacterium violaceum.

A new antibiotic, aerocavin, has been isolated from fermentation broths of a non-pigmented strain of Chromobacterium violaceum. The structure 1 was deduced from its spectroscopic properties and X-ray diffraction analysis. Aerocavin exhibits activity in vitro against Gram-positive and Gram-negative bacteria.

Anti-Bacterial Agents

Exposure of firefighters to diesel emissions in fire stations.

Personal sampling techniques were used to evaluate firefighter exposure to particulates from diesel engine emissions. Selected fire stations in New York, Boston and Los Angeles were studied. Firefighter exposure to total particulates increased with the number of runs conducted during an 8-hr period. In New York and Boston where the response level ranged from 7 to 15 runs during an 8-hr shift, the resulting exposure levels of total airborne particulates from diesel exhaust were 170 to 480 micrograms/m3 (TWA). Methylene chloride extracts of the diesel particulates averaged 24% of the total. The authors' findings suggest that additional research is necessary to assess fire station concentrations of vehicle diesel exhaust that may have adverse health consequences to firefighters.

Air Pollutants, Occupational

Xylocandin: a new complex of antifungal peptides. I. Taxonomy, isolation and biological activity.

Xylocandin is a complex of novel peptides with potent antifungal activity that is produced by Pseudomonas cepacia ATCC 39277. The complex was isolated from the fermentation broth by extraction with butanol-methanol, 9:1, followed by collection of the precipitate formed upon concentration of the solvent extract. Purification was effected by chromatography on reversed phase and size exclusion gels followed by TLC on silica gel. These techniques afforded eight components: A1, A2, B1, B2, C1, C2, D1 and D2. A mixture of the two closely related components, xylocandins A1 and A2, displayed potent anticandidal and antidermatophytic activities in vitro. The activity was diminished by the presence of serum or vaginal washings. No antibacterial activity was demonstrable.

Animals

Effect of aerosol size on the blood lead distribution of industrial workers.

The size distribution measurements of lead aerosol from a brass foundry and primary lead smelter are used to simulate blood lead distributions applying a pharmacokinetic model developed by Bernard. The predicted distribution of blood lead levels determined using the actual size distribution of lead aerosol are compared to the blood lead levels predicted according to the model assumptions adopted in setting the OSHA lead standard. In the furnace area of the smelter and the pouring area of the foundry the predicted mean blood lead level is higher than that found in the standard whereas, in the smelter's sintering and mixing operation the blood lead level is less than that suggested by the standard. The data support the conclusion that size-selective sampling needs to be considered for incorporation into the OSHA lead standard.

Aerosols

In vivo and in vitro release of cyanide from neurotoxic aminonitriles.

Cyanide release from neurotoxic aminonitriles was measured following in vitro incubation with both microsomes and liver slices. Investigation of cyanide released as urinary thiocyanate following ip aminonitrile administration to rats was also measured. The yield of cyanide in the in vivo study, as measured by the mole percent of administered dose, was greatest from dimethylaminonitrile (DMAA), followed by trimethylaminopropionitrile (TMAPN), dimethylaminopropionitrile (DMAPN), 3,3'-iminodipropionitrile (IDPN), dimethylaminobutyronitrile (DMABN), and monomethylaminopropionitrile (MMAPN). Urinary excretion of thiocyanate accounted for 48.9% of the administered DMAA, 11.6% of TMAPN, 8.0% of DMAPN, 6.8% of IDPN, 3.1% of DMABN, and 1.8% of MMAPN. Incubation of aminonitriles and related compounds with microsomes or liver slices from rats yielded measurable quantities of cyanide from all the compounds tested except for DMABN, TMABN, and succiononitrile. Quantitative evaluation of the yield of formaldehyde by demethylation following microsomal incubation was also determined. The signs of acute toxicity in rats after ip administration of KCN were similar only to those in rats administered DMAA.

Aminopropionitrile

Particle bounce in a personal cascade impactor: a field evaluation.

The collection characteristics of five types of substrates (collection surfaces) used in personal cascade impactors were evaluated for particle bounce in the laboratory with lead dioxide dust, and in the field with brass pouring fume and brass grinding dust. The substrates tested were uncoated stainless steel, silicon grease-coated stainless steel, oil-saturated Millipore membrane filter, oil-saturated Teflon membrane filter and oil-saturated sintered stainless steel. The use of coated and uncoated stainless steel plates to collect lead dioxide dust produced no difference in measured mass median diameter (MMD); however, with brass grinding dust, there was a 50% decrease in measured MMD when uncoated stainless steel substrates were used, as compared with coated stainless steel substrates. Oil-saturated Millipore membrane surfaces gave consistently lower MMDs than coated stainless steel surfaces. Coated and uncoated stainless steel gave similar MMDs when used to sample brass pouring fume. Oil-saturated Teflon membrane and oil-saturated sintered metal, surfaces for which the collection efficiency is presumed to be independent of the particle loading, gave MMDs similar to those measured for grease-coated stainless steel. The implications of these comparisons are discussed. It is concluded that bounce characteristics are strongly dependent on aerosol material and the suitability of collection surfaces needs to be determined by field evaluation.

Aerosols