Biomedical subjects

Li Feng

Publications and source records attributed to Li Feng.

At least 19 recordsLinked to original sources

PubMed2026

Rab10 coordinates SADS-CoV non-lytic egress through the ERGIC-TGN-lysosome trafficking pathway.

Swine acute diarrhea syndrome coronavirus (SADS-CoV) is a bat-originated alphacoronavirus that causes devastating enteric disease in neonatal piglets and possesses significant potential for cross-species transmission. While the early stages of the coronavirus life cycle have been extensively characterized, the host factors indispensable for virion assembly and subsequent export remain largely enigmatic. Here, by performing a genome-wide CRISPR-Cas9 knockout screen using a recombinant icSADS-CoV-GFP reporter virus, we identified the small GTPase Rab10 as a critical host dependency factor for SADS-CoV infection. Viral life cycle analysis revealed that Rab10 is not required for viral attachment, entry, or initial genome replication, but is essential for the virion transport and non-lytic egress. Rab10 deficiency markedly reduced the extracellular release of viral RNA, viral proteins, and infectious progeny, as well as the secretion of SADS-CoV virus-like particles. Confocal imaging showed that Rab10 and viral protein-positive intracellular structures were associated with LMAN1, TGN46, and LAMP1 positive compartments. These findings support a model in which Rab10 coordinates a virus-containing vesicles trafficking pathway associated with ERGIC-TGN-lysosome compartments. Mechanistically, Rab10 facilitates the loading of the viral envelope (E) protein into transport vesicles derived from the ERGIC. Rab10 associates with the SADS-CoV E protein, and mapping analyses implicated the C-terminal PDZ-binding motif, particularly residue V75, in efficient Rab10 association and viral release. Collectively, our findings identify Rab10 as a host regulator of SADS-CoV non-lytic egress and highlight the E-Rab10 interaction and the vesicular trafficking machinery as a potential target for developing antiviral strategies.

Animals↗

PubMed2026

MS4A3 as a potential prognostic biomarker for colon cancer: integrated analysis of expression patterns and immune cell infiltration.

BACKGROUND: Membrane Spanning 4-Domains A3 (MS4A3) has been confirmed to possess significant tumor-suppressive potential in various malignancies. However, its expression characteristics and clinical prognostic value in colon cancer (CC) still lack systematic and in-depth investigation. This study aimed to systematically investigate the expression pattern, prognostic value, immune microenvironment association, and biological function of MS4A3 in CC through integrated bioinformatics analyses and experimental validation. METHODS: This study utilized The Cancer Genome Atlas-Colon Adenocarcinoma (TCGA-COAD) cohort to screen for genes significantly associated with CC and combined multiple independent Gene Expression Omnibus (GEO) datasets to validate the expression patterns and prognostic significance of MS4A3. Key biological pathways were identified through gene set enrichment analysis (GSEA), and tumor immune infiltration characteristics were evaluated using the CIBERSORT algorithm. Additionally, the expression of MS4A3 and its impacts on cellular functions were validated at the cellular level through quantitative real-time polymerase chain reaction (qRT-PCR), Western blot, Cell Counting Kit-8 (CCK-8), EdU, Transwell, and TUNEL assays. RESULTS: Analysis of public datasets revealed that MS4A3 is significantly downregulated in CC tissues, and its low expression is an independent risk factor for shortened overall survival (OS). GSEA indicated that MS4A3 downregulation is closely associated with the aberrant activation of the pentose phosphate pathway. Immune infiltration analysis showed that low MS4A3 expression is closely linked to the enrichment of M2 macrophages and neutrophils, as well as the upregulation of multiple immune checkpoint genes. In vitro experiments further confirmed that MS4A3 was lowly expressed in CC cell lines. Its overexpression significantly inhibited CC cell viability, proliferation, migration, and invasion, while simultaneously promoting cell apoptosis. CONCLUSIONS: MS4A3 expression is significantly decreased in CC tissues and is significantly correlated with poor prognosis, suggesting that this gene may serve as a potential prognostic biomarker.

MS4A3↗

PubMed2026

Chemical and sensory profiling of fermented, washed, and artificially flavored coffee beans: Insights into flavour quality, authenticity, and food safety implications.

This study establishes an integrated framework combining chemical profiling, sensory analysis, and molecular mechanism evaluation to compare flavour quality and authenticity among fermented, washed, and artificially flavored coffees. GC × GC-TOF-MS and UHPLC-HRMS showed that fermented samples had markedly higher ester and aromatic alcohol levels (total esters 74.5 ± 7.8 mg kg-1; phenylethanol 27.5 ± 3.2 mg kg-1, p < 0.01), enhancing fruity-floral notes. Washed coffees contained the highest organic acid concentrations (45.2 ± 3.8 mg kg-1, p < 0.01), supporting brightness and umami. Artificially flavored coffees exhibited elevated exogenous aromatics (vanillin 21.5 ± 3.1 mg kg-1) but significantly fewer Maillard products (p < 0.05) and reduced flavour retention (55% after 14 days). Molecular docking revealed higher theoretical binding affinities for naturally generated compounds, suggesting a potential molecular basis for their greater sensory persistence. The framework supports constructing coffee quality fingerprints and verifying flavour authenticity.

Flavoring Agents↗

PubMed2026

Methylation profiling of normal tissue adjacent to breast tumors reveals two distinct groups with divergent tumor microenvironment features.

We previously identified diverse genetic evolutionary patterns in whole-genome sequencing of paired normal tissue adjacent to tumor (NAT) and tumor tissues from Hong Kong breast cancer (HKBC) patients. Here, we investigated whether DNA methylation (DNAm) contributes to NAT heterogeneity and shapes the tumor microenvironment (TME). Genome-wide DNAm profiling was performed on paired NAT and tumor tissues from 188 HKBC patients using the Infinium 850 K array. RNA-seq data were available for 76 NATs and 177 tumors. Cellular composition was inferred using MethylCIBERSORT, CIBERSORTx, and EpiDISH, and histopathologic features were assessed on 115 H&E-stained sections. Unsupervised clustering identified two distinct NAT subtypes with divergent TME characteristics. Cluster 1 (N = 139) showed higher epithelial and fibroblast content and enrichment of estrogen response pathways. Cluster 2 (N = 49) exhibited an immune-metabolic phenotype characterized by increased fat and immune cells, stromal disruption, inflammatory pathway activation, and greater macrophage infiltration. Cluster 2 patients also demonstrated significantly younger epigenetic age estimated using multiple epigenetic clocks. These DNAm-defined NAT subtypes and associated TME features were validated in 97 NAT samples from TCGA breast cancer patients. Overall, our findings identify DNAm-driven NAT heterogeneity with distinct TME landscapes, providing new insights into field cancerization and tumor evolution in breast cancer.

Journal Article↗

PubMed2026

Genome-Guided Discovery of Antimalarial 4-Amino-2,4-Pentadienoate-Containing Cyclolipodepsipeptides.

4-Amino-2,4-pentadienoate-containing cyclolipodepsipeptides (APD-CLDs) represent a structurally distinctive family of natural products known for their selective activity against hypoxic cancer cells. To explore the structural diversity of APD-CLDs, we have identified and prioritized cryptic APD-CLD biosynthetic gene clusters (BGCs) for compound discovery. Using a combination of genetic and chemical methods, we successfully activated three dormant BGCs, leading to the discovery of 12 new APD-CLDs. These newly discovered metabolites significantly expanded the diversity of the APD-CLD family, with chloromalamides and arabimalamides representing the first halogenated and glycosylated members, respectively. Unexpectedly, chloromalamides and arabimalamides exhibited potent antiplasmodial activity, with IC50 values in the 25-161 nM range against drug-sensitive and multidrug-resistant Plasmodium falciparum strains. Phenotypic studies revealed arabimalamide B halted parasite development during the asexual blood stage life cycle, resulting in enlarged digestive vacuoles, dispersed hemozoin, and ultimately reduced reinvasion efficiency. These phenotypes are reminiscent of the effect of chloroquine and other 4-aminoquinoline drugs, suggesting that arabimalamides may disrupt the parasite's heme detoxification mechanism. Biosynthetic studies identified key scaffold-forming and modifying enzymes, including a rare membrane glycosyltransferase in arabimalamide biosynthesis. Together, these findings unveil APD-CLDs as new antimalarial lead scaffolds and set the stage for structural diversification and optimization.

Antimalarials↗

PubMed2026

Integrative subtyping by bile acid metabolism identifies CLCA1/UGT2A3/ZG16 as markers of immune dysfunction and poor prognosis in colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) is the primary driver of cancer-related death and illness across the world. Despite the full-scale shift of the treatment approach for some colorectal cancer patients due to the use of immune checkpoint inhibitors (ICIs), primary resistance still poses a huge challenge to clinicians. Bile acid metabolism is involved in the pathogenesis of CRC. However, its particular function in shaping the tumor immune microenvironment (TIME) and its effect on prognosis and immune treatment response remain unclear. METHODS: Based on the transcriptome and clinical data from The Cancer Genome Atlas-Colon Adenocarcinoma (TCGA-COAD) cohort, we performed unsupervised consensus clustering and classified patients into different molecular subtypes according to bile acid metabolism. We subsequently compared overall survival (OS), immune cell infiltration levels, and differentially expressed genes among the subtypes. In addition, protein-protein interaction (PPI) network and Cox proportional hazards regression were used to identify key hub genes. Finally, the expression of these crucial hub genes was validated in the Gene Expression Omnibus (GEO) cohort and independent clinical patients. RESULTS: The bile-low group showed a significant reduction in OS time (p = 0.0049). The infiltration levels of CD8+ T cells (p < 0.05) and M1 macrophages (p < 0.01) were significantly higher in the bile-low group than in the bile-high group. We identified three key genes-CLCA1, UGT2A3, and ZG16-and found that they all were downregulated in tumor tissues across the TCGA-COAD and GEO datasets, as well as in independent clinical samples. Survival analysis showed that high CLCA1 expression was significantly associated with favorable overall survival (p < 0.001), whereas UGT2A3 (p = 0.23) and ZG16 (p = 0.17) did not reach statistical significance. The three hub genes were negatively correlated with the (TIDE) score (CLCA1: R = - 0.24, p < 0.001; UGT2A3: R = - 0.15, p = 0.0022; ZG16: R = - 0.14, p = 0.0039). CONCLUSION: Our findings suggest that bile acid metabolism could shape the TIME via key genes CLCA1, UGT2A3, and ZG16, and subsequently modify CRC prognosis and immunotherapy responses. These genes may serve as potential prognostic indicators and mechanistic mediators linking bile acid metabolism to T-cell dysfunction, offering insights for future combination strategies targeting the metabolism-barrier-immunity axis.

CLCA1↗

PubMed2025

Harnessing Landscape Genomics to Evaluate Genomic Vulnerability and Future Climate Resilience in an East Asia Perennial.

In this era of rapid climate change, understanding the adaptive potential of organisms is imperative for buffering biodiversity loss. Genomic forecasting provides invaluable insights into population vulnerability and adaptive potential under diverse climatic conditions, thereby facilitating management interventions and bolstering shaping species-specific germplasm conservation strategies. We primarily employed landscape genomics approaches, leveraging single-nucleotide polymorphisms obtained through whole-genome resequencing of 201 individuals across 43 Rheum palmatum complex populations, to pinpoint adaptive variation and its significance in the context of future climates, delineate seed zones, and establish guidelines for ex situ germplasm conservation. The species complex exhibited strong signatures of local adaptation and differential genomic vulnerabilities across its distribution range, with eastern lineage populations facing significant maladaptation risks under future climate scenarios. Using diverse datasets of putatively adaptive loci and climate change scenarios, we delineated three distinct seed zones within the species' range, estimated varying sample sizes per zone to capture most adaptive diversity, and predicted shifts in seed zone centroids ranging from 48.3 to 359.3 km from historical distributions to mitigate climate change impacts. Collectively, our findings underscore the importance of integrating genomic and environmental data to forecast the adaptive trajectory of an East Asian perennial under anticipated climate changes, guide seed zone delineation for germplasm conservation and enhance population resilience. These results provide a blueprint for designing targeted conservation strategies and restoration plans in other imperilled species.

Climate Change↗

PubMed2006

Mitochondrial respiration defects in cancer cells cause activation of Akt survival pathway through a redox-mediated mechanism.

Cancer cells exhibit increased glycolysis for ATP production due, in part, to respiration injury (the Warburg effect). Because ATP generation through glycolysis is less efficient than through mitochondrial respiration, how cancer cells with this metabolic disadvantage can survive the competition with other cells and eventually develop drug resistance is a long-standing paradox. We report that mitochondrial respiration defects lead to activation of the Akt survival pathway through a novel mechanism mediated by NADH. Respiration-deficient cells (rho(-)) harboring mitochondrial DNA deletion exhibit dependency on glycolysis, increased NADH, and activation of Akt, leading to drug resistance and survival advantage in hypoxia. Similarly, chemical inhibition of mitochondrial respiration and hypoxia also activates Akt. The increase in NADH caused by respiratory deficiency inactivates PTEN through a redox modification mechanism, leading to Akt activation. These findings provide a novel mechanistic insight into the Warburg effect and explain how metabolic alteration in cancer cells may gain a survival advantage and withstand therapeutic agents.

Apoptosis↗

PubMed2006

Synthesis, crystal structure, magnetic property and nuclease activity of a new binuclear cobalt(II) complex.

One new binuclear Co(II) complex of N,N,N',N'-tetrakis(2-benzimidazolylmethyl)-2-hydroxyl-1,3-diaminopropane (HL), [Co(2)L(mu(2)-Cl)](ClO(4))(2) x 3CH(3)CN x C(2)H(5)OC(2)H(5) (1), has been synthesized and its crystal structure and magnetic properties are shown. In 1, each Co(II) atom has a distorted trigonal bipyramidal geometry with a N(3)OCl donor set. The central two Co(II) atoms are bridged by one alkoxo-O atom and one Cl atom with the Co1-Co2 separation of 3.239 A. Susceptibility data of 1 indicate strong intramolecular antiferromagnetic coupling of the high-spin Co(II) atoms. In this paper, the interaction with calf thymus DNA was investigated by UV absorption and fluorescent spectroscopy. Results show the complex binds to ct-DNA with a intercalative mode. The interaction between complex 1 and pBR322 DNA has also been investigated by submarine gel electrophoresis, noticeably, the complex exhibits effective DNA cleavage activity in the absence of any external agents.

Animals↗

PubMed2006

Caspase-3-dependent activation of calcium-independent phospholipase A2 enhances cell migration in non-apoptotic ovarian cancer cells.

Calcium-independent phospholipase A(2) (iPLA(2)) plays a pivotal role in phospholipid remodeling and many other biological processes, including inflammation and cancer development. iPLA(2) can be activated by caspase-3 via a proteolytic process in apoptotic cells. In this study we identify novel signaling and functional loops of iPLA(2) activation leading to migration of non-apoptotic human ovarian cancer cells. The extracellular matrix protein, laminin-10/11, but not collagen I, induces integrin- and caspase-3-dependent cleavage and activation of overexpressed and endogenous iPLA(2). The truncated iPLA(2) (amino acids 514-806) generates lysophosphatidic acid and arachidonic acid. Arachidonic acid is important for enhancing cell migration toward laminin-10/11. Lysophosphatidic acid activates Akt that in turn acts in a feedback loop to block the cleavage of poly-(ADP-ribose) polymerase and DNA fragmentation factor as well as prevent apoptosis. By using pharmacological inhibitors, blocking antibodies, and genetic approaches (such as point mutations, dominant negative forms of genes, and siRNAs against specific targets), we show that beta(1), but not beta(4), integrin is involved in iPLA(2) activation and cell migration to laminin-10/11. The role of caspase-3 in iPLA(2) activation and cell migration are supported by several lines of evidence. 1) Point mutation of Asp(513) (a cleavage site of caspase-3 in iPLA(2)) to Ala blocks laminin-10/11-induced cleavage and activation of overexpressed iPLA(2), whereas mutation of Asp(733) to Ala has no such effect, 2) treatment of inhibitors or a small interfering RNA against caspase-3 results in decreased cell migration toward laminin-10/11, and 3) selective caspase-3 inhibitor blocks cleavage of endogenous iPLA(2) induced by laminin-10/11. Importantly, small interfering RNA-mediated down-regulation of endogenous iPLA(2) expression in ovarian carcinoma HEY cells results in decreased migration toward laminin, suggesting that our findings are pathophysiologically important.

Apoptosis↗

PubMed2006

A boronic-chalcone derivative exhibits potent anticancer activity through inhibition of the proteasome.

Chalcones and their derivatives have been shown to have potent anticancer activity. However, the exact mechanisms of cytotoxic activity remain to be established. In this study, we have evaluated a series of boronic chalcones for their anticancer activity and mechanisms of action. Among the eight chalcone derivatives tested, 3,5-bis-(4-boronic acid-benzylidene)-1-methyl-piperidin-4-one (AM114) exhibited most potent growth inhibitory activity with IC50 values of 1.5 and 0.6 microM in 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and colony formation assay, respectively. The cytotoxic activity of AM114 was shown to be associated with the accumulation of p53 and p21 proteins and induction of apoptosis. Mechanistic studies showed that AM114 treatment inhibited the chymotrypsin-like activity of the 20S proteasome in vitro, leading to a significant accumulation of ubiquitinated p53 and other cellular proteins in whole cells. In vitro studies showed that AM114 did not significantly disrupt the interaction of p53 and murine double minute 2 protein. It is noteworthy that AM114 as a single agent was preferentially toxic to cells with wild-type p53 expression, whereas combination of this compound with ionizing radiation (IR) significantly enhanced the cell-killing activity of IR in both wild-type p53 and p53-null cells. Together, these results indicate that the boronic chalcone derivative AM114 induces significant cytotoxic effect in cancer cells through the inhibition of the cellular proteasome and provide a rationale for the further development of this class of compounds as novel cancer chemotherapeutic agents.

Antineoplastic Agents↗

PubMed2006

Lysophosphatidic acid is constitutively produced by human peritoneal mesothelial cells and enhances adhesion, migration, and invasion of ovarian cancer cells.

Lysophosphatidic acid (LPA) is both a potential marker and a therapeutic target for ovarian cancer. It is critical to identify the sources of elevated LPA levels in ascites and blood of patients with ovarian cancer. We show here that human peritoneal mesothelial cells constitutively produce LPA, which accounts for a significant portion of the chemotactic activity of the conditioned medium from peritoneal mesothelial cells to ovarian cancer cells. Both production of LPA by peritoneal mesothelial cells and the chemotactic activity in the conditioned medium can be blocked by HELSS [an inhibitor of the calcium-independent phospholipase A(2) (iPLA(2))] and AACOCF(3) [an inhibitor of both cytosolic PLA(2) (cPLA(2)) and iPLA(2)]. Moreover, cell-based enzymatic activity assays for PLA(2) indicate that peritoneal mesothelial cells have strong constitutive PLA(2) activity. Receptors for LPA, LPA(2), and LPA(3) are involved in the conditioned medium-induced chemotactic activity. Invasion of ovarian cancer cells into peritoneal mesothelial cells has also been analyzed and shown to require PLA(2), LPA receptors, and the mitogen-activated protein/extracellular signal-regulated kinase kinase/extracellular signal-regulated kinase signaling pathway. Thus, we show here, for the first time, that human peritoneal mesothelial cells constitutively produce bioactive lipid signaling molecules, such as LPA, via iPLA(2) and/or cPLA(2) activities. Conditioned medium from peritoneal mesothelial cells stimulate migration, adhesion, and invasion of ovarian cancer cells, and may play similar roles in vivo.

Arachidonic Acids↗

PubMed2006

Pharmaceutical and immunological evaluation of a single-dose hepatitis B vaccine using PLGA microspheres.

The objective of the study was to investigate the feasibility of a single-dose hepatitis B vaccine based on three kinds of poly (D, L)-lactide-co-glicolide acid (PLGA) microspheres. PLGA microspheres loaded with recombinant hepatitis B surface antigen (HBsAg) were formulated using a double emulsion microencapsulation technique. The pharmaceutical characteristics of size, surface morphology, protein loading efficiency, antigen integrity, release of HBsAg-loaded PLGA microspheres and degradation of the polymer in vitro were evaluated. The degradation of the polymer corresponded with the composition of the polymer (lactide/glycolide ratio), molecular weight of the polymer (viscosity) and morphology of the microspheres. These PLGA microspheres were able to continuously release antigen under conditions that mimic the environment in vivo. The single subcutaneous injection of HBsAg-loaded PLGA50/50 microspheres, PLGA75/25 microspheres and a mixture of PLGA50/50, PLGA75/25, and PLGA50/50-COOH microspheres in mice resulted in comparable serum antibody titers to those of three injections of the conventional aluminum adjuvant formulated HBsAg vaccine. Based on these findings in vitro and in vivo, it was concluded that HBsAg was successfully loaded into the PLGA microspheres, which can auto-boost an immune response, and the HBsAg-loaded PLGA microsphere is a promising candidate for the controlled delivery of a vaccine.

Animals↗

PubMed2006

[Advances in researches on the mechanism and prevention of chronic kidney graft dysfunction].

In the 21st century, one of the focuses in the field of organ transplantation is the prevention of chronic kidney graft dysfunction (CKGD) and the furtherance of the long-term survival rate. Researches on the mechanism and prevention of CKGD have made progress in the important immune and nonimmune factors of CKGD. Researchers' endeavors to establish the model of CKGD in the animals such as inbreeding pigs; to develop new drugs which are characterized by high efficacy, low toxicity, low cost, and synergy when used together with immune depressants available from natural medicine; and to probe deeply into the mechanism and prevention of CKGD, will be the important aspects in the field of organ transplantation in the 21st century.

Graft Survival↗

PubMed2006

[Immunogenicity of single-dose HBsAg-PLGA controlled release microspheres in mice].

AIM: To investigate the level of immune response and the immune mechanism of the single-dose hepatitis B surface antigen (HBsAg)-poly (d, l)-lactide-co-glicolide acid (PLGA) microspheres in BALB/c mice. METHODS: Three kind of HBsAg-PLGA microspheres, HBsAg-PLGA50/50-COOH microspheres, HBsAg-PLGA75/25 microspheres and HBsAg-PLGA50/50 microspheres, were prepared by double emulsion microencapsulation technique used three kinds of PLGA with different L/G ratio. The single-dose of HBsAg-PLGA microspheres was subcutaneously injected into BALB/c mice at the dose of 7.5 microg HBsAg per mouse. The conventional aluminum-adjuvant vaccine was subcutaneously injected at 0, 1 and 2 month as positive control. In certain time interval, the induced immune level of total antibody was detected by enzyme linked immunosorbent assay (ELISA). For subclass of IgG antibody and cytokines studies, the dose of HBsAg was 2.5 microg per mouse. RESULTS: The HBsAg-PLGA microspheres could successfully induce a humoral immune response in BALB/c mice. Compared with the conventional aluminum-adjuvant vaccine, the antibody response of the HBsAg-PLGA50/50-COOH microspheres was significantly lower than the group received three injections of aluminum-adjuvant vaccine (P < 0.01) except for a higher priming response during the early 6 weeks. The results were ascribed to the relatively rapid degradation charactics of PLGA50/50-COOH polymer. The immune response for the HBsAg-PLGA50/50 microspheres and HBsAg-PLGA75/25 microspheres were comparable to the group administered with aluminum-adjuvant vaccine (P > 0.05) which was due to the sustained degradation of PLGA50/50 and PLGA75/25 polymer. CONCLUSION: The HBsAg-PLGA microsphere is a promising candidate for the controlled delivery of a vaccine which does not require multiple injections.

Animals↗

PubMed2006

[Influence of ambroxol on paraquat-induced lung tissue injury and change of pulmonary surfactant-associated protein A in the experimental rats].

OBJECTIVE: To investigate the influence of ambroxol on paraquat poisoning induced acute lung tissue injury and the change of pulmonary surfactant associated protein A in the experimental rats. METHODS: One hundred and twenty healthy adult male Sprague-Dawley rats were randomizedly assigned into normal saline (NS) group (n = 24), paraquat poisoning induced lung tissue injury model (PQ) group (n = 48) and ambroxol treatment (AT) group (n = 48). The indexes were observed among the three groups comprising the mortality rate, the change of arterial blood PaCO(2) and PaO(2), the ratio of wet to dry lung tissue (W/D), the change of the lung tissue under light and electric microscope respectively, and the expression of pulmonary surfactant associated protein A. RESULTS: The mortality rate of rats in the PQ group was 50.0% on the seventh day while the mortality rate in the AT group was 25.0%. The level of arterial blood PaCO(2) in the PQ group (6.94 +/- 0.8) kPa was significantly higher than that in the AT group (6.12 +/- 0.5) kPa and the NS group (4.6 +/- 0.4) kPa. The level of arterial blood PaO(2) in the PQ group (6.98 +/- 1.1) kPa was significantly lower than that in the AT group (8.25 +/- 0.7) kPa and the NS group (12.7 +/- 0.8) kPa. There were significant differences among the groups (P < 0.05). The degree of lung tissue injury was severe in PQ group and relieved in AT group. The expression of pulmonary surfactant associated protein A was significantly decreased in PQ group 13.22% +/- 2.21% on the seventh day, compared with that in the AT group (21.82% +/- 3.67%) (P < 0.05). The expression of pulmonary surfactant associated protein A in AT group was significantly higher in the AT group (18.97% +/- 0.91%) than that in the PQ group on the seventh day (P < 0.05). CONCLUSION: Ambroxol plays a role in facilitating synthesis and secretion of pulmonary surfactant protein A and relieves the lung tissue injury induced by paraquat poisoning.

Ambroxol↗

PubMed2005

[Preparation, release and immunogenicity evaluation of HBsAg-PLGA microspheres].

OBJECTIVE: To investigate microencapsulation technique, release of HBsAg-PLGA microspheres and degradation of the polymer in vitro, and the level of immune response after the single-dose HBsAg-PLGA microspheres subcutaneously injected (sc) to BALB/c mice. METHODS: HBsAg-PLGA microspheres were prepared by double emulsion microencapsulation technique with orthogonal experiments. The pharmaceutical characteristics of size and surface morphology, antigen loading efficiency, release of HBsAg-PLGA microspheres and degradation of the polymer in vitro, and the level of immune response after single sc of PLGA microspheres in BALB/c mice were investigated. RESULTS: The concentration of PVA was the significant factor affecting the particle size (P<0.05). The release of protein from the microspheres was controlled mainly by the bulk erosion of polymer matrix. When single sc of HBsAg-PLGA microspheres mixed with different formulations, the immunogenicity effect was comparable to that of the aluminium adjuvant vaccine. CONCLUSION: The single-dose HBsAg-PLGA microspheres mixture with different release behavior is a promising candidate for controlled delivery vaccine.

Animals↗

PubMed2005

Mitochondrial manganese-superoxide dismutase expression in ovarian cancer: role in cell proliferation and response to oxidative stress.

Superoxide dismutases (SODs) are important antioxidant enzymes responsible for the elimination of superoxide radical (O(2)(-)). The manganese-containing SOD (Mn-SOD) has been suggested to have tumor suppressor function and is located in the mitochondria where the majority of O(2)(-) is generated during respiration. Although increased reactive oxygen species (ROS) in cancer cells has long been recognized, the expression of Mn-SOD in cancer and its role in cancer development remain elusive. The present study used a human tissue microarray to analyze Mn-SOD expression in primary ovarian cancer tissues, benign ovarian lesions, and normal ovary epithelium. Significantly higher levels of Mn-SOD protein expression were detected in the malignant tissues compared with normal tissues (p < 0.05). In experimental systems, suppression of Mn-SOD expression by small interfering RNA caused a 70% increase of superoxide in ovarian cancer cells, leading to stimulation of cell proliferation in vitro and more aggressive tumor growth in vivo. Furthermore, stimulation of mitochondrial O(2)(-) production induced an increase of Mn-SOD expression. Our findings suggest that the increase in Mn-SOD expression in ovarian cancer is a cellular response to intrinsic ROS stress and that scavenging of superoxide by SOD may alleviate the ROS stress and thus reduce the simulating effect of ROS on cell growth.

Animals↗