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Biomedical subjects

Jun Zhao

Publications and source records attributed to Jun Zhao.

At least 19 recordsLinked to original sources

Inheritance of the epigenetic signature and reduced intermuscular bone phenotype acquired via DNA methylation editing of the runx2 b promoter in zebrafish.

The presence of intermuscular bones (IBs) can directly affect the economic value of aquaculture fish. Although genome editing can create IB-free fish by knocking out key IB-related genes, such as runx2b, the associated DNA sequence alterations raise food safety and health concerns, limiting its breeding applications. In this study, we used CRISPR/dCas9-mediated epigenome-editing technology targeting the runx2 b promoter in zebrafish to alter DNA methylation patterns without changing the DNA sequence. Our results showed that higher runx2 b promoter methylation patterns significantly inhibited eGFP mRNA expression levels in the recombinant plasmid. Using the CRISPR/dCas9-Dnmt7 system to enhance methylation of the zebrafish runx2b promoter, we observed a significant decrease in runx2 b mRNA expression levels in the F0 generation. The IBs in the 11 th-16 th muscle segments of the adult F0 fish were significantly shorter compared with the controls. Inbreeding of fish was used to produce F1 and F2 offspring that retained these high promoter methylation levels, along with persistent runx2b expression suppression and IB development inhibition. Transcriptome sequencing analysis suggested that increasing runx2 b promoter methylation levels may synergistically induce additional epigenetic modifications, potentially affecting the PPAR signaling pathway and FoxO transcription factor regulation, which appears to inhibit osteoblast proliferation and differentiation. Overall, this study demonstrates an innovative application of epigenetic editing technology for aquaculture breeding. By precisely regulating the expression patterns of key genes for economically important traits while preserving genomic DNA integrity, this approach provides a theoretical foundation and technical support for improving fish economic traits.

Animals↗

Large-scale genomic analysis places Chinese CC398 as a persistent human-associated MSSA lineage apart from the dominant global LA-MRSA clade.

Staphylococcus aureus clonal complex (CC)398 has emerged as a dominant livestock-associated methicillin-resistant S. aureus (LA-MRSA) lineage worldwide; however, its evolutionary trajectory and regional diversification remain incompletely understood. We developed a core-genome multilocus sequence typing (cgMLST) scheme with hierarchical clustering and applied it to over 30,000 S. aureus genomes, revealing frequent cross-border transmission of CC398. Subsequent time-calibrated phylogenetic analysis placed the most recent common ancestor at 1942 (95% CI: 1939-1945), with the human-to-livestock host jump around 1969 (95% CI: 1968-1972). Chinese CC398 exhibits a distinct trajectory: unlike the LA-MRSA lineages dominating Europe and North America, Chinese isolates are predominantly human-associated methicillin-susceptible S. aureus (HA-MSSA), forming unique East Asia-specific phylogroups (SAP1, SAP2, and AP1-AP3), with distinct resistance and virulence profiles. The LA lineage remains limited in China, with multinational mixed clusters emerging only after 2019. Analysis of global transmission networks revealed a significant correlation between LA-CC398 spread and international trade in fresh swine products, while no such correlation was observed for the human-associated lineage. Beyond the established lineage markers tet(M) and scn, our analysis identified additional differentially distributed genes, including cadC-a chromosomal cadmium resistance regulator-as a novel HA-lineage-enriched gene whose functional role in host adaptation remains to be determined. This study reveals that CC398 followed fundamentally different evolutionary paths in China versus Western countries, challenging a one-size-fits-all model of its dissemination.IMPORTANCEThis study illustrates how large-scale microbial genomics can resolve the evolutionary origins and regional diversification of bacterial pathogens. By applying a novel cgMLST scheme to over 30,000 S. aureus genomes, we show that CC398 followed fundamentally different evolutionary paths in China versus Western countries-challenging the prevailing model of uniform global dissemination-and that livestock-associated MRSA expansion is closely linked to international trade in fresh pork products. These findings highlight the need for integrated surveillance across human, animal, and trade interfaces to anticipate the emergence and spread of zoonotic pathogens.

Staphylococcus aureus↗

Synovial short-lived plasma cells mediate adalimumab resistance in rheumatoid arthritis via MIF-CD74 axis-driven, partially TNF-α-independent inflammation.

OBJECTIVE: Synovial plasma cell infiltration predicts inadequate response to adalimumab in patients with rheumatoid arthritis (RA), yet the cellular and molecular mechanisms underlying this association remain unclear. This study aimed to dissect the functional heterogeneity of synovial plasma cells between adalimumab responders and non-responders at single-cell resolution, and to identify the molecular pathways driving treatment resistance. METHODS: This study was based on a prospective clinical cohort of 101 RA patients receiving adalimumab, from which synovial tissues of 8 patients (4 ACR20 responders and 4 non-responders) were profiled by 10x Genomics single-cell RNA sequencing (66,539 high-quality cells). A systematic ligand-receptor screening was performed to identify candidate signaling axes. Core findings were validated at four levels: an independent single-cell validation cohort (n = 4), external bulk RNA-seq cohorts (GSE15602, GSE47726), multiplex immunofluorescence on synovial tissues (n = 9 per group), and in vitro functional experiments using patient-derived peripheral blood monocyte-derived macrophages stimulated with recombinant human MIF under pharmacological intervention with adalimumab, the MIF inhibitor ISO-1, and an anti-CD74 neutralizing antibody. RESULTS: Plasma cells were significantly enriched in non-responder synovium, with a heterogeneous pattern characterized by quantitative accumulation of long-lived plasma cells (LLPCs) and functional dominance of short-lived plasma cells (SLPCs): SLPCs contributed 58.15% of total ribosomal module activity and preferentially overexpressed MIF. Systematic screening of 145 candidate ligand-receptor pairs identified MIF-CD74 as the only axis satisfying all four independent evidence layers. Tissue-level immunofluorescence confirmed that approximately 95% of synovial CD138+ plasma cells in non-responders co-expressed MIF, compared with approximately 45% in responders. In vitro, rh-MIF upregulated macrophage activation markers (CD74, CD80, CD86, HLA-DR) and induced IL-6 and TNF-α secretion. Adalimumab neutralized supernatant TNF-α but failed to suppress MIF-driven IL-6 and IL-1β activation, whereas ISO-1 and anti-CD74 effectively blocked MIF-induced effects at all levels examined. These findings were replicated in patient-derived PBMC macrophages. CONCLUSION: In adalimumab-resistant RA, a functionally active SLPC subset drives partially TNF-α-independent macrophage inflammation through the MIF-CD74 axis, representing a resistance pathway not fully addressed by anti-TNF therapy. Targeting MIF or CD74 blocked this axis in vitro, supporting MIF-CD74-directed precision intervention.

Adalimumab↗

TWIST2-dependent transcriptional activation of TPI1 mediates TGF-β1-driven fibroblast activation in pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal interstitial lung disease characterized by aberrant profibrotic signaling and excessive extracellular matrix deposition, accompanied by fibroblast-to-myofibroblast transition. Despite extensive investigation, the molecular mechanisms underlying IPF pathogenesis remain incompletely understood. Here, we investigated the role of triosephosphate isomerase 1 (TPI1) in IPF progression and its regulation by transforming growth factor-β (TGF-β) signaling. Loss-of-function analyses identified TPI1 as a downstream effector of TGF-β1, as its knockdown markedly suppressed fibrotic marker expression, fibroblast proliferation, and migration. Mechanistically, TWIST2 was shown to function as a direct transcriptional regulator of TPI1, binding to its promoter and promoting transcriptional activation. Rescue experiments further confirmed that the TWIST2-TPI1 axis is central to the progression of pulmonary fibrosis. Notably, knockdown of either TPI1 or TWIST2 effectively attenuated TGF-β1-induced fibrotic phenotypes. Collectively, these findings define the TGF-β1/TWIST2/TPI1 signaling axis as an important regulator of pathogenic fibroblast behavior and pro-fibrotic responses through transcriptional control of TPI1, highlighting its potential as a therapeutic target for IPF.

Twist-Related Protein 1↗

Benzoic acid inhibits peach root growth and lateral root emergence by disrupting auxin homeostasis through salicylic acid accumulation.

We established a non-sterile root transformation system in peach seedlings. Using this system, we demonstrated that BA treatment inhibits plant growth and lateral root emergence by SA-mediated disruption of auxin distribution. Allelopathic autotoxins, particularly benzoic acid (BA), are recognized as primary contributors to peach (Prunus persica) replant disease; however, the molecular mechanisms by which BA disrupts root development remain poorly understood. BA treatment significantly reduced stem and root length and inhibited lateral root emergence without affecting lateral root initiation. To investigate the underlying mechanism at cellular resolution, we established a non-sterile Agrobacterium rhizogenes-based root transformation system achieving 27.11% transformation efficiency. Auxin biosynthesis (PpYUC10), influx transport (PpAUX1), and response (PpARF19) genes were markedly downregulated following BA treatment. Transgenic roots expressing the DR5::GUS auxin reporter exhibited reduced DR5 activity in root tips and suppressed expression in tissues surrounding lateral root primordia, indicating impaired auxin signaling at both developmental sites. Hormone profiling revealed a non-significant trend toward reduced auxin metabolites alongside significant accumulation of salicylic acid (SA), an auxin-antagonistic hormone, and its storage conjugate SA 2-O-β-glucoside. Supporting a causal role for SA, exogenous SA phenocopied BA-induced root growth inhibition, whereas co-treatment with IAA or the SA-biosynthesis inhibitor aminoindan-1-phosphonic acid (AIP) significantly rescued lateral root number and root fresh weight. Multi-treatment RNA-seq identified "response to auxin" and "response to salicylic acid" as the most enriched GO terms in BA-treated roots, and AIP treatment restored the expression of key auxin-related genes while reversing BA-induced SA-pathway changes. Together, these findings suggest that BA-induced SA accumulation suppresses auxin biosynthesis, transport, and signaling, thereby inhibiting peach root growth and lateral root emergence. This study elucidates the molecular basis of BA autotoxicity and establishes a transformation platform for functional genomic studies in Prunus.

Indoleacetic Acids↗

Genomic Profiling, Risk Stratification, and Post-Transformation Treatment Outcomes in Patients with Transformed Small-Cell Lung Cancer: A Multicenter Analysis.

BACKGROUND: Transformed small-cell lung cancer (T-SCLC) is an increasingly recognized resistance mechanism in EGFR-mutant lung adenocarcinoma. This study aimed to identify early predictors of histologic transformation and evaluate post-transformation treatment outcomes. METHODS: We retrospectively collected 163 T-SCLC patients from five Chinese centers. Next-generation sequencing was performed on 60 EGFR-mutant patients, including 47 paired primary-transformed samples. Integrated genomic and clinical analyses were conducted to delineate molecular features and survival outcomes. RESULTS: Among 150 EGFR-mutant patients, the median time to SCLC transformation was 25.8 months and median post-transformation overall survival (OS) was 14.2 months. Clinical and survival data for the 13 EGFR wild-type patients are reported descriptively given the limited sample size. Among 108 treatment-evaluable patients, first-line EGFR-TKI plus chemotherapy, chemotherapy alone, and immune checkpoint inhibitors (ICIs) plus chemotherapy yielded median progression-free survival (PFS) of 6.2, 5.30, and 4.07 months (P = 0.041) and median OS of 21.2, 27.6, and 13.6 months (P = 0.193). In later-line therapy, taxane-based regimens achieved a median PFS of 6.93 months, outperforming camptothecin-based (1.13 months) and other regimens (1.90 months; P = 0.049). High evolutionary diversity was associated with shorter post-transformation OS (6.77 vs. 11.10 months), with restricted cubic spline analysis showing a nonsignificant trend toward a nonlinear association (P = 0.055).Age, RB1/NTRK1 mutation, and secondary T790M mutation were identified as independent risk factors and integrated into a predictive model with high accuracy. CONCLUSIONS: This study establishes a clinically applicable model for early prediction and risk stratification of SCLC transformation. Taxane-based regimens emerge as a promising later-line therapeutic option for T-SCLC.

Humans↗

Heterogeneous chemistry of butanol and decanol with sulfuric acid: implications for secondary organic aerosol formation.

Recent environmental chamber studies suggest that acid-catalyzed reactions between alcohols and aldehydes in the condensed phase lead to the formation of hemiacetals and acetals, enhancing secondary organic aerosol (SOA) growth. We report measurements of heterogeneous uptake of butanol and decanol on liquid H2SO4 in the range of 62-84 wt % and between 273 and 296 K. Both alcohols exhibit two distinct types of uptake behaviors (partially irreversible vs totally irreversible uptake), depending on the acid concentration and temperature. For the partially irreversible uptake, a fraction of the alcohol was physically absorbed while the other fraction underwent irreversible reaction. For the totally irreversible uptake, the alcohols were completely lost onto the sulfuric acid. The Henry's law solubility constant (H*) was determined from the time-dependent uptake, while the reactive uptake coefficients were calculated from the time-independent irreversible loss. Coexistence of butanol or decanol with octanal or decanal did not show enhanced uptake of the aldehydes in the sulfuric acid. Protonation and dissolution likely account for the reversible uptake, while formation of alkyl sulfate or dialkyl sulfate explains irreversible uptake of the alcohols. The results suggest that heterogeneous uptake of larger alcohols is unlikely of significant importance in the lower atmosphere except in the case of freshly nucleated aerosols that may have high acid concentrations.

Journal Article↗

An autosomal dominant progressive congenital zonular nuclear cataract linked to chromosome 20p12.2-p11.23.

PURPOSE: To map and to identify the causal gene for autosomal dominant congenital cataract (ADCC) in a Chinese family. METHODS: A four-generation family with a history of progressive congenital cataracts was investigated. Twenty-three members of the family were examined ophthalmologically. Blood samples were collected from twenty-nine family members for genetic linkage analysis. Two-point LOD scores were calculated. Multi-point linkage analysis and haplotype construction were performed to define the optimal cosegregating interval. Direct sequence analysis of the candidate gene, beaded filament structural protein 1, filensin (BFSP1) in the critical region was carried out. RESULTS: Fifteen family members were affected with autosomal dominant progressive congenital zonular nuclear cataract (ADPCZNC). The maximum two-point LOD Score of 6.02 was obtained for marker D20S904 (theta=0). The cataract locus in this family was mapped to chromosome 20p12.2-p11.23, a 9.34 Mb (16.37 cM) interval between markers D20S186 and D20S912. Although BFSP1 was in this critical region, we found no evidence that the condition in the family was caused by a BFSP1 mutation. CONCLUSIONS: We have mapped the genetic locus of ADPCZNC to chromosome 20p12.2-p11.23 in an ADCC family. This is the first time ADPCZNC was linked to this region.

Asian People↗

The nano-Au self-assembled glassy carbon electrode for selective determination of epinephrine in the presence of ascorbic acid.

Gold nanoparticles were self-assembled to the modified glassy carbon electrode (GC) with cysteamine (CA) to prepare the nano-Au/CA/GC modified electrode. The electrochemical behavior of epinephrine (EP) on the modified electrode was explored with cyclic voltammetry (CV) and differential pulse voltammetry (DPV). Epinephrine gave a pair of redox peaks at E(pa)=0.190 mV and E(pc)=-0.224 mV (versus SCE), respectively. The nano-Au/CA/GC modified electrode shows an excellent electrocatalytic activity for the oxidation of EP. The modified electrode could be used to determine EP in the presence of ascorbic acid (AA). The response of catalytic current with EP concentration shows a linear relation in the range of 1.0 x 10(-7) to 5.0 x 10(-4) mol L(-1) with the correlation coefficient of 0.998. The detection limit is 4.0 x 10(-8) mol L(-1). The modified electrode exhibited a good reproducibility, sensitivity and stability for the determination of EP injection.

Ascorbic Acid↗

Immunological evaluation of SW-HSA conjugate on goats.

Locoweeds cause significant livestock poisoning and economic loss all over the world. The purpose of this study was to investigate the immune effects of locoweed toxin, swainsonine (SW) and human serum albumin (HSA) conjugate (SW-HSA), on goats. Twenty-four Sannon goats were randomly separated into immune control group (eight goats), immune poisoning group I (six goats), immune poisoning group II (six goats) and poisoning control group (four goats). Immune control group, immune poisoning groups I and II were first vaccinated with SW-HSA conjugate. The poisoning control group, immune poisoning groups I and II were then fed with 10.0 g/kg BW/day dry powder of Oxytropis kansuensis Bunge everyday morning. The immune control group was supplied with an alfalfa-based diet. Blood samples of these experimental animals were collected at different time interval. Immunoassay was performed using indirect ELISA and E-rosette technique. The results show that, after second booster immunization: (1) anti-SW antibody level in some goats increased to 2(8), which proves that SW-HSA conjugate can induce experimental animals to produce high-level anti-SW antibody in their bodies; (2) the high-level antibody in their bodies could maintain 30 days, and decreased gradually after poisoning experiment (in our experiment, there was a return of the antibody level on day 21 after poisoning experiment); (3) the decreasing of the E-rosette rate of the immune poisoning group was delayed 14 days, which suggests that SW-HSA could low down the loss of the immunity of the goats; (4) swainsonine concentration in the blood was significantly lower (p<0.01) in the immune poisoning groups than that in the poisoning control group, and there was no significant difference (p>0.01) between the two immune poisoning groups within the poisoning experiment.

Animals↗

A novel comonomer-free light-cured glass-ionomer cement for reduced cytotoxicity and enhanced mechanical strength.

OBJECTIVE: The objective of this study was to develop a novel comonomer-free light-cured glass-ionomer system based on the 4-arm star-shape poly(acrylic acid). The mechanical strengths and in vitro cytotoxicity of the formed system were evaluated and compared with those of several representative commercial glass-ionomer cements. MATERIALS AND METHODS: The 4-arm poly(acrylic acid) was synthesized using ATRP and tethered with glycidyl methacrylate (GM). The GM-tethered polymer was formulated with water, photo-initiators, and Fuji II LC filler. Fuji II, Fuji II LC and Vitremer were used for comparison. Compressive strength (CS) and MTT assay were used as tools to evaluate the mechanical strengths and in vitro cytotoxicity of the cements, respectively. RESULTS: The experimental cement exhibited significantly high compressive, diametral tensile and flexural strengths as compared to commercial glass-ionomer cements, Fuji II, Fuji II LC and Vitremer. The effects of polymer/water (P/W) ratio, GM-grafting ratio, glass powder/polymer liquid (P/L) ratio and aging in water on strengths were significant. Similar to conventional glass-ionomer cement Fuji II, the eluates from the experimental cement showed little in vitro cytotoxicity to Balb/c mouse fibroblast cells, as compared to Fuji II LC and Vitremer that contain HEMA as a comonomer. CONCLUSIONS: It appears that this novel comonomer-free light-cured glass-ionomer cement will be a promising dental restorative because it demonstrated significantly improved mechanical strengths and almost no in vitro cytotoxicity as compared to current commercial light-cured glass-ionomer cements.

Acrylic Resins↗

Novel injectable and in situ curable glycolide/lactide based biodegradable polymer resins and composites.

Novel in situ polymerizable liquid three-arm biodegradable oligomeric polyesters based upon glycolic acid (GA), L-lactic acid (LLA), and their copolymers are synthesized and characterized. Injectable and in situ curable polymer neat resins and their composites formulated with bioabsorbable beta-tricalcium phosphate are prepared at room temperature using photo- and redox-initiation systems, respectively. The cured neat resins show the initial compressive yield strength (YCS, MPa), modulus (M, MPa), ultimate compressive strength (UCS, MPa), and toughness (T, kN mm), ranging from 4.0 to 20.1, 201.5 to 730.2, 82.7 to 310.5, and 1.02 to 3.93. The cured composites show the initial YCS, M, UCS and T, ranging from 27.7 to 56.4, 1440 to 4870, 81.6 to 158.9, and 0.94 to 1.97. Increasing GA/LLA ratio increases all the initial compressive strengths of both neat resins and composites. Increasing filler content increases YCS and M but decreases UCS and T. A diametral tensile strength test shows the same trend as a compressive strength test. There seems to be an optimal flexural strength for the composite at the filler content around 43%. An increasing molar ratio increases curing time but decreases the degree of conversion (DC). An increasing filler content increases curing time but decreases exotherm and DC. During the course of degradation, all the materials show a burst degradation behavior within 24 h, followed by an increase in CS. The poly(glycolic acid) neat resin completely loses its strength at around Day 45. The composites completely lose their strengths at different time intervals, depending on their molar ratio and filler content. The degradation rate is found to be molar ratio and filler-content dependent.

Absorbable Implants↗

Efficient screening method of the thiopurine methyltransferase polymorphisms for patients considering taking thiopurine drugs in a Chinese Han population in Henan Province (central China).

BACKGROUND: Thiopurine S-methyltransferase (TPMT) is an enzyme that catalyzed the S-methylation of thiopurine drugs. TPMT activity exhibits an interindividual variability, mainly as a result of genetic polymorphism. Patients with intermediate or deficient TPMT activity are at risk for toxicity after receiving standard doses of thiopurine drugs. We determined a cut-off concentration of the TPMT activity assay less than which genotyping of the TPMT gene should be performed. In addition, the influence of hemodialysis on TPMT activity in uremic patients was examined. METHODS: In 248 healthy subjects and 30 uremic patients, PCR-based methods were used to analyze the most common functional mutations TPMT2, 3A, 3B and 3C. A HPLC assay was used to measure erythrocyte TPMT activity in the whole population. RESULTS: Seven TPMT3C heterozygotes were identified, while TPMT2, 3A and 3B alleles were not detected in 248 healthy subjects. The frequency of TPMT3C allele was 1.4% (7/496). The TPMT activity in healthy subjects was normally distributed, ranged from 6.09 to 28.65 nmol/h/ml pRBC with a mean of 16.03 +/- 4.16 nmol/h/ml pRBC. The cut-off for high TPMT activity and intermediate TPMT activity was 10.07 nmol/h/ml pRBC. There were 19 intermediate activity healthy subjects (7.7%) and 229 high activity healthy subjects (92.3%), and no TPMT deficiency subject was found. All of the 229 healthy subjects with high activity had no mutant alleles, while 7 of the 19 subjects with intermediate activity had a mutant allele. Phenotypes were in good agreement with genotypes for 95% of subjects. The uremic patients were all homozygous for the wild-type allele whose TPMT activity was activated significantly before hemodialysis compared with TPMT activity after hemodialysis. CONCLUSIONS: We defined the cut-off values for the TPMT phenotyping assay at 10.07 nmol/h/ml pRBC, less than which additional genotyping elucidates the individual risk for drug therapy. In uremic patients, TPMT activity is increased by some uremic factors, and dialysis shifted their TPMT activity close to that of a healthy control group.

Adult↗

Durable protection of rhesus macaques immunized with a replicating adenovirus-SIV multigene prime/protein boost vaccine regimen against a second SIVmac251 rectal challenge: role of SIV-specific CD8+ T cell responses.

Previously, priming with replication-competent adenovirus-SIV multigenic vaccines and boosting with envelope subunits strongly protected 39% of rhesus macaques against rectal SIV(mac251) challenge. To evaluate protection durability, eleven of the protected and two SIV-infected unimmunized macaques that controlled viremia were re-challenged rectally with SIV(mac251). Strong protection was observed in 8/11 vaccinees, including two exhibiting <50 SIV RNA copies. Decreased viremia compared to naïve controls was observed in the other three. The SIV-infected unimmunized macaques modestly controlled viremia but exhibited CD4 counts < or =200, unlike the protected macaques. Durable protection was associated with significantly increased SIV-specific ELISPOT responses and lymphoproliferative responses to p27 at re-challenge. After CD8 depletion, 2 of 8 re-challenged, protected vaccinees maintained <50 SIV RNA copies; SIV RNA emerged in 6. Re-appearance of CD8 cells and restoration of SIV-specific cellular immunity coincided with viremia suppression. Overall, cellular immunity induced by vaccination and/or low-level, inapparent viremia post-first SIV(mac251) challenge, was associated with durable protection against re-challenge.

Adenoviridae↗

Direct electrochemistry behavior of cytochrome c/L-cysteine modified electrode and its electrocatalytic oxidation to nitric oxide.

Cytochrome c (Cyt c) was successfully immobilized on L-cysteine modified gold electrode by multicyclic voltammetry method. The electrochemical behavior of Cyt c on the L-cysteine modified electrode was explored. In 0.10 M, pH 7.0 phosphate buffer solution (PBS), Cyt c showed a quasi-reversible electrochemical redox behavior with E(pc)=0.180 V, E(pa)=0.208 V (versus Ag/AgCl). The Cyt c/L-cysteine modified electrode gave an excellent electrocatalytic activity towards the oxidation of nitric oxide, and the catalysis currents were proportional to the nitric oxide concentration in the range of 7.0 x 10(-7) to 1.0 x 10(-5) M, the linear regression equation is I (microA)=-0.124-0.003 C(NO) (microM), with a correlation coefficient 0.996, The detection limit was 3.0 x 10(-7) M (times the ratio of signal to noise, S/N=3).

Adsorption↗

Effect of total phenolics from Laggera alata on acute and chronic inflammation models.

The anti-inflammatory effect of total phenolics from Laggera alata (TPLA) was evaluated with various in vivo models of both acute and chronic inflammations. In the acute inflammation tests, TPLA inhibited significantly xylene-induced mouse ear oedema, carrageenan-induced rat paw oedema and acetic acid-induced mouse vascular permeability. In the carrageenan-induced rat pleurisy model, TPLA significantly suppressed inflammatory exudate and leukocyte migration, reduced the serum levels of lysozyme (LZM) and malondialdehyde (MDA), increased the serum levels of superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX), and also decreased the contents of total protein, nitric oxide (NO) and prostaglandin E(2) (PGE(2)) in the pleural exudates. In the chronic inflammation experiment, TPLA inhibited significantly cotton pellet-induced rat granuloma. These results indicated that TPLA possesses potent anti-inflammatory activity on acute and chronic inflammation models. Its anti-inflammatory mechanisms are probably associated with the inhibition of prostaglandin formation, the influence on the antioxidant systems, and the suppression of LZM release. Furthermore, the total phenolic content of Laggera alata and its main component type was quantified, and its principle components were isolated and authenticated. Acute toxicity studies revealed that TPLA up to an oral dose of 8.5 g/kg body weight was almost nontoxic in mice.

Acute Disease↗

A rat model of bone cancer pain induced by intra-tibia inoculation of Walker 256 mammary gland carcinoma cells.

This study described a modified rat model of bone cancer pain. Syngeneic Walker 256 mammary gland carcinoma cells were injected into the tibia medullary cavity via intercondylar eminence. Series of tests were carried out including bone radiology, bone histology, ambulatory pain, thermal hyperalgesia, mechanical allodynia, weight bearing ability, and electrophysiological recording from primary afferent fibers. The rats inoculated with carcinoma cells showed significant ambulatory pain, mechanical allodynia, and reduction in weight bearing, as well as increased incidence of spontaneous activity in Abeta fibers in affected limb, whereas PBS (vehicle) or heat-killed cells (sham) injected rats showed no significant difference in comparison to normal rats. The pain hypersensitive behaviors were aggravated with time and destruction of bone. Interestingly, mechanical allodynia was also observed in the contralateral limb, indicating the involvement of 'mirror image' pain in bone cancer pain. In summary, the present study provided a useful and easily established rat model of bone cancer pain which will contribute to further study of the mechanisms underlying cancer pain.

Action Potentials↗