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Biomedical subjects

Gang Li

Publications and source records attributed to Gang Li.

At least 37 records · Page 2Linked to original sources

alpha-Fetoprotein shields hepatocellular carcinoma cells from apoptosis induced by tumor necrosis factor-related apoptosis-inducing ligand.

The interference of alpha-fetoprotein (AFP) with the apoptosis induced by tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in Bel 7402 cells was investigated in the current study. The results showed a moderate degree of drug-resistance of Bel 7402 cells to TRAIL. The caspase-3 cascade was the main pathway involved in TRAIL-induced apoptosis, which was virtually abolished in the presence of AFP. TRAIL together with antibody against AFP was able to accelerate the death of tumor cells. This study suggests the possibility a therapeutic strategy for improving clinical treatment of liver tumor with TRAIL could be effected through antagonizing the shelter effect of AFP.

Antibodies, Monoclonal↗

Precision measurement of ultralow losses of an asymmetric optical microcavity.

The losses of the transmission, absorption, and scattering of optical mirrors govern the extraction efficiency of a nonclassical state that is generated inside a cavity. By measuring the reflectivities and transmittances and the matching factors from both sides of a super-mirror-made microcavity at various mode-matching efficiencies, the transmission losses and the unwanted losses, including the absorption and scatter losses, of the left and right cavity mirrors were both determined at the parts-per-million level.

Journal Article↗

Development of a monoclonal antibody-based enzyme-linked immunosorbent assay for the analysis of glycyrrhizic acid.

Glycyrrhizic acid (GL) is a major active compound of licorice. The specific monoclonal antibody (MAb) (designated as 8F8A8H42H7) against GL was produced with the immunogen GL-BSA conjugate. The dissociation constant (Kd) value of the MAb was approximately 9.96x10(-10) M. The cross reactivity of the MAb with glycyrrhetic acid was approximately 2.6%. The conventional indirect competitive enzyme-linked immunosorbent assay (icELISA) and simplified icELISA adapted with a modified procedure were established using the MAb. The IC50 value and the detect range by the conventional icELISA were 1.1 ng mL-1 and 0.2-5.1 ng mL-1, respectively. The IC50 value and the detect range by the simplified icELISA were 5.3 ng mL-1 and 1.2-23.8 ng mL-1, respectively. The two icELISA formats were used to analyze GL contents in the roots of wild licorice and different parts of cultivated licorice (Glycyrrhiza uralensis Fisch). The results obtained with the two icELISAs agreed well with those of the HPLC analysis. The correlation coefficient was more than 0.98 between HPLC and the two icELISAs. The two icELISAs were shown to be appropriate, simple, and effective for the quality control of raw licorice root materials.

Animals↗

Synthesis of single crystal CdMoO4 octahedral microparticles via microemulsion-mediated route.

The single crystal octahedra of tetragonal CdMoO4 were synthesized on large scale via a microemulsion-mediated hydrothermal route at 120 degrees C for 10 h. The structures, compositions and morphologies of the as-prepared products were characterized by X-ray power diffraction pattern, field emission scanning electronic microscopy, transmission electron microscopy. Further studies reveal that the octahedral CdMoO4 crystal has eight equivalent exposed crystal faces {101}. The possible growth mechanism of the CdMoO4 octahedral is based on the anisotropic growth habit of CdMoO4 crystals and the selective absorption of surfactant molecules CTAB on the faces of the prime crystals, and the reaction time, composition of the microemulsions and temperature have considerable effects on the final morphology of CdMoO4.

Journal Article↗

Role of p53 up-regulated modulator of apoptosis and phosphorylated Akt in melanoma cell growth, apoptosis, and patient survival.

Malignant melanoma is an aggressive and chemoresistant form of skin cancer characterized by rapid metastasis and poor patient prognosis. The development of innovative therapies with improved efficacy is critical to treatment of this disease. Here, we show that aberrant expression of two proteins, p53 up-regulated modulator of apoptosis (PUMA) and phosphorylated Akt (p-Akt), is associated with poor patient survival. Using tissue microarray analysis, we found that patients exhibiting both weak PUMA expression and strong p-Akt expression in their melanoma tumor tissue had significantly worse 5-year survival than patients with either weak PUMA or strong p-Akt expression alone (P < 0.001). Strikingly, no patients exhibiting strong PUMA expression and weak p-Akt expression in primary tumor tissue died within 5 years of diagnosis. We propose a two-pronged therapeutic strategy of (a) boosting PUMA expression and (b) inhibiting Akt phosphorylation in melanoma tumor tissue. Here, we report that a recombinant adenovirus containing human PUMA cDNA (ad-PUMA) efficiently inhibits human melanoma cell survival in vitro, rapidly induces apoptosis, and dramatically suppresses human melanoma tumor growth in a severe combined immunodeficient mouse xenograft model. In melanoma cells strongly expressing p-Akt, we show that Akt/protein kinase B signaling inhibitor-2 (API-2; a small-molecule Akt inhibitor) reduces cell survival in a dose- and time-dependent manner and enhances ad-PUMA-mediated growth inhibition of melanoma cells. Finally, we show that, by combining ad-PUMA and API-2 treatments, human melanoma tumor growth can be inhibited by >80% in vivo compared with controls. Our results suggest that a strategy to correct dysregulated PUMA and p-Akt expression in malignant melanoma may be an effective therapeutic option.

Adenoviridae↗

Concise review: multipotent mesenchymal stromal cells in blood.

Peripheral blood-derived multipotent mesenchymal stromal cells circulate in low number. They share, most although not all, of the surface markers with bone marrow-derived multipotent mesenchymal stromal cells, possess diverse and complicated gene expression characteristics, and are capable of differentiating along and even beyond mesenchymal lineages. Although their origin and physio-pathological function are still unclear, their presence in the adult peripheral blood might relate to some interesting but controversial subjects in the field of adult stem cell biology, such as systemic migration of bone marrow-derived multipotent mesenchymal stromal cells and the existence of common hematopoietic-mesenchymal precursors. In this review, current studies/knowledge about peripheral blood-derived multipotent mesenchymal stromal cells is summarized, and the above-mentioned topics are discussed.

Animals↗

Prognostic significance of nuclear factor-kappaB p105/p50 in human melanoma and its role in cell migration.

Transcriptional factor nuclear factor-kappaB (NF-kappaB) family has been shown to play an important role in tumor pathogenesis and serve as a potential target in cancer therapy. However, it is necessary to clarify the specific functions of NF-kappaB members, which would provide the basis for the selective blockade and reduction of therapeutic side effects resulting from unspecific inhibition of NF-kappaB members. In this study, we explored the role of NF-kappaB p105/p50 in melanoma pathogenesis in vitro and in vivo. We found that the expression of NF-kappaB p105/p50 significantly increased in dysplastic nevi, primary melanoma, and metastatic melanoma compared with normal nevi (P = 0.0004, chi(2) test). Furthermore, NF-kappaB p105/p50 nuclear staining increased with melanoma progression and strong NF-kappaB p105/p50 nuclear staining was inversely correlated with disease-specific 5-year survival of patients with tumor thickness >2.0 mm (P = 0.014, log-rank test). Multivariate Cox regression analysis revealed that nuclear expression of NF-kappaB p105/p50 is an independent prognostic factor in this subgroup. Moreover, we found that up-regulation of NF-kappaB p50 enhanced melanoma cell migration, whereas small interfering RNA knockdown inhibited cell migration. In addition, overexpression of NF-kappaB p50 induced RhoA activity and Rock-mediated formation of stress fiber in melanoma cells. Taken together, our data indicate that NF-kappaB p105/p50 may be an important marker for human melanoma progression and prognosis as well as a potentially selective therapeutic target.

Cell Line, Tumor↗

Molecular and cytogenetic characterization of an Oryza officinalis-O. sativa chromosome 4 addition line and its progenies.

The wild species Oryza officinalis Wall. ex Watt (2n = 24, CC) is a valuable genetic resource for rice (O. sativa L., 2n = 24, AA) breeding and genomics research. Genomic in situ hybridization (GISH) and molecular approaches were used to determine the nature and composition of the additional chromosome in a monosomic alien addition line (MAAL) of O. officinalis and its backcross progenies. The extra wild species chromosome in the MAAL (2n = 2x = 25) was a mosaic one, comprising of the long arm of chromosome 4 from O. officinalis and the short arm from O. sativa. Comparative analysis showed that O. sativa and O. officinalis shared high synteny of restriction fragment length polymorphism (RFLP) markers and low synteny of simple sequence repeat (SSR) markers. A DNA methylation alteration was revealed at C619 in the MAAL and progenies. Analysis of progenies of the MAAL indicated that introgression segments were small in size and introgression was not evenly distributed along the long arm. One recombination hot spot between C513 and RG177 was identified, which is in a gene-rich region.

Blotting, Southern↗

Mesenchymal stem cells in immunoregulation.

Mesenchymal stem cells are present within the bone marrow cavity and serve as a reservoir for the continuous renewal of various mesenchymal tissues. Recent studies suggest that mesenchymal stem cells modulate immune reactions in vitro and escape from immune surveillance in vivo. We provide herein a discussion of issues including the current research progress on the in vitro interactions of mesenchymal stem cells with multiple subsets of immune cells (dendritic cells, T cells, B cells and NK cells), in vivo transplantation outcomes, the possible underlying mechanisms, future research directions as well as potential clinical implications.

Animals↗

Development of a monoclonal antibody-based enzyme-linked immunosorbent assay for the herbicide chlorimuron-ethyl.

Hybridomas secreting a monoclonal antibody (mAb) against the herbicide chlorimuron-ethyl (CE) were produced by fusing the mouse myeloma cell line (SP2/0) with splenocytes from a mouse immunized against the conjugate of the sulfonamide moiety of CE and bovine serum albumin (BSA). The mAb, designated 1F5C5A10, had very weak affinity with metsulfuron, ethametsulfuron, pyrazosulfuron, bensulfuron, and chlorsulfuron. Two mAb-based indirect competitive enzyme-linked immunosorbent assays (icELISA) were developed. A conventional icELISA (icELISA-I) showed a concentration of half-maximum inhibition (IC(50)) of 11.6 ng/mL with a dynamic range of 1.6-84 ng/mL. A simplified icELISA (icELISA-II) had an IC(50) of 28.7 ng/mL and a dynamic range of 2.2-372 ng/mL. The two assays were tested on spiked water and soil samples. CE (1-500 ng/mL) fortified in water samples could be analyzed directly without any sample preparation by both immunoassays with an average recovery between 74 and 114%. icELISA-II, but not icELISA-I, was able to accurately analyze the herbicide residues in the crude soil extracts with recoveries between 99 and 129% without obvious matrix effects due to its lesser amount of sample used. In contrast to icELISA-I, icELISA-II is more convenient, whereas it consumes more reagents of coating antigen and goat anti-mouse IgG-peroxidase.

Animals↗

Genetic background controls tumor development in PTEN-deficient mice.

PTEN is one of the most frequently mutated tumor suppressor genes in human cancers. Germ line mutations of PTEN have been detected in three rare autosomal-dominant disorders. However, identical mutations in the PTEN gene may lead to different symptoms that have traditionally been described as different disorders, such as Cowden disease, Lhermitte-Duclos disease, and Bannayan-Zonana syndromes. This lack of genotype-phenotype correlation prompted us to directly test the possible effects of genetic background or modifier genes on PTEN-controlled tumorigenesis using genetically engineered mouse models. In this study, we generated two animal models in which either exon 5 (Pten(Delta5)) or promoter to exon 3 (Pten(-)) of the murine Pten gene were deleted and compared phenotypes associated with individual mutations on two genetic backgrounds. We found that the onset and spectrum of tumor formation depend significantly on the genetic background but less on the type of mutation generated. Our results suggest that PTEN plays a critical role in cancer development, and genetic background may influence the onset, the spectrum, and the progression of tumorigenesis caused by Pten mutation.

Alleles↗

Long-lived effector/central memory T-cell responses to severe acute respiratory syndrome coronavirus (SARS-CoV) S antigen in recovered SARS patients.

The role of cell-mediated immunity in human SARS-CoV infection is still not well understood. In this study, we found that memory T-cell responses against the spike (S) protein were persistent for more than 1 year after SARS-CoV infection by detecting the production of IFN-gamma using ELISA and ELISpot assays. Flow cytometric analysis showed that both CD4(+) and CD8(+) T cells were involved in cellular responses against SARS-CoV infection. Interestingly, most of SARS-CoV S-specific memory CD4(+) T cells were central memory cells expressing CD45RO(+) CCR7(+) CD62L(-). However, the majority of memory CD8(+) T cells revealed effector memory phenotype expressing CD45RO(-) CCR7(-) CD62L(-). Thus, our study provides the evidence that SARS-CoV infection in humans can induce cellular immune response that is persistent for a long period of time. These data may have an important implication in the possibility of designing effective vaccine against SARS-CoV infection, specifically in defining T-cell populations that are implicated in protective immunity.

Adult↗

Phosphatized polar lobe-forming embryos from the Precambrian of southwest China.

In developing embryos of some extant spiralian animals, polar lobe formation is one of the symmetry-breaking mechanisms for segregation of maternal cytoplasmic substances to certain blastomeres and not others. Polar lobe formation leads to unique early cleavage morphologies that include trilobed, J-shaped, and five-lobed structures. Fossil embryos similar to modern lobeforming embryos are recognized from the Precambrian Doushantuo Formation phosphates, Weng'an, Guizhou Province, China. These embryos are abundant and form a developmental sequence comparable to different developing stages observed in lobe-forming embryos of extant spiralians. These data imply that lobe formation is an evolutionarily ancient process of embryonic specification.

Animals↗

Aberrant expression of collagen triple helix repeat containing 1 in human solid cancers.

PURPOSE: The collagen triple helix repeat containing 1 (CTHRC1) is a promigratory protein first found to be expressed during rat tissue repair process. Recent preliminary results revealed CTHRC(1) mRNA in melanoma and breast cancer. However, the full significance of CTHRC1 to human carcinogenesis remains unclear. This study is to further characterize the clinical and functional relevance of CTHRC1 in melanoma and other human solid cancers. EXPERIMENTAL DESIGN: First, semiquantitative immunohistochemistry analysis was done on 304 clinically annotated, paraffin-embedded biopsies representing different stages of melanoma progression. Then, short interfering RNA was used to inhibit expression of CTHRC1 protein for migration analysis on cultured melanoma cells. Finally, the CTHRC1 expression was surveyed in 310 samples representing 19 types of human solid cancers. RESULTS: In benign nevi and noninvasive melanoma biopsies, there was little CTHRC1 protein expression. In contrast, in invasive primary melanomas, there was a significant increase of CTHRC1 protein (P < 0.01, chi(2) test). There was a further increase of CTHRC1 protein in metastatic melanoma specimens compared with nonmetastatic lesions (P < 0.01, chi(2) test). In addition, inhibition of CTHRC1 expression resulted in decreased cell migration in vitro. Finally, transcription survey in 19 types of human solid cancers revealed aberrant CTHRC1 expression in 16 cancer types, especially cancers of the gastrointestinal tract, lung, breast, thyroid, ovarian, cervix, liver, and the pancreas. CONCLUSIONS: Aberrant expression of CTHRC1 is widely present in human solid cancers and seems to be associated with cancer tissue invasion and metastasis. It potentially plays important functional roles in cancer progression, perhaps by increasing cancer cell migration.

Amino Acid Sequence↗

Leucine zipper-like domain is required for tumor suppressor ING2-mediated nucleotide excision repair and apoptosis.

The plant homodomain (PHD) of ING2 was shown to regulate p53-dependent apoptosis through phosphoinositides signaling. However, the role of a predicted leucine zipper-like (LZL) motif in N-terminus of ING2 is unclear. Here, we show that LZL motif is critical for the proper functions of ING2 in DNA repair, apoptosis and chromatin remodeling after UV irradiation. Deletion of LZL domain also abrogated the association between ING2 and p53, but not between ING2 and p300, suggesting that ING2 modulates p53-dependent chromatin remodeling, apoptosis and DNA repair by functioning as a scaffold protein to mediate the interaction between p53 and p300.

Acetylation↗

Bioreactor expansion of human adult bone marrow-derived mesenchymal stem cells.

Supplementation of mesenchymal stem cells (MSCs) during hematopoietic stem cell (HSC) transplantation alleviates complications such as graft-versus-host disease, leading to a speedy recovery of hematopoiesis. To meet this clinical demand, a fast MSC expansion method is required. In the present study, we examined the feasibility of using a rotary bioreactor system to expand MSCs from isolated bone marrow mononuclear cells. The cells were cultured in a rotary bioreactor with Myelocult medium containing a combination of supplementary factors, including stem cell factor and interleukin-3 and -6. After 8 days of culture, total cell numbers, Stro-1(+)CD44(+)CD34(-) MSCs, and CD34(+)CD44(+)Stro-1(-) HSCs were increased 9-, 29-, and 8-fold, respectively. Colony-forming efficiency-fibroblast per day of the bioreactor-treated cells was 1.44-fold higher than that of the cells without bioreactor treatment. The bioreactor-expanded MSCs showed expression of primitive MSC markers endoglin (SH2) and vimentin, whereas markers associated with lineage differentiation, including osteocalcin (osteogenesis), type II collagen (chondrogenesis), and C/EBP-alpha (CCAAT/enhancer-binding protein-alpha) (adipogenesis), were not detected. Upon induction, the bioreactor-expanded MSCs were able to differentiate into osteoblasts, chondrocytes, and adipocytes. We conclude that the rotary bioreactor with the modified Myelocult medium reported in this study may be used to rapidly expand MSCs.

Aged↗

Rapid demonstration of diversity of sulfatide molecular species from biological materials by MALDI-TOF MS.

By combining the partition method for enrichment of sulfatides without any chromatographic procedures and the preparation method of lysosulfatides, we succeeded in analyzing these sulfated glycosphingolipids from biological materials by matrix-assisted laser desorption and ionization time-of-flight mass spectrometry (MALDI-TOF MS) to reduce the complexity of mass fragmentation patterns within a day. We found that sulfated GalCer (HSO3-3Gal beta 1Cer) (SM4s [galactosylsulfatide]) was composed of different species. While composition of SM4s specifically depended on source materials, it always contained hydroxy fatty acids of various degrees. In addition to the common sphingoid 4-sphingenine (d18:1), uncommon/unusual sphingoids phytosphingosine (4-hydroxysphinganine) (t18:0), eicosasphinganine (d20:0), 4-eicosasphingenine (d20:1), and sphingadienine (d18:2) were easily detected. Finally, in addition to SM4s, sulfatide sulfated LacCer (HSO3-3Gal beta 4Glc beta 1Cer) (SM3 [sulfated lactosylceramide]) and sulfated Gg3Cer (GalNAc beta 4(HSO3-3)Gal beta 4Glc beta 1Cer) (SM2 [sulfated gangliotriaosylceramide]) were clearly detected in renal tubule cells. The major SM4s was composed of ceramides possessing d18:1 with C22 hydroxy fatty acids (C22:0 h), C23:0 h, and C24:0 h, whereas the major SM3/SM2 were composed of ceramides possessing t18:0 with C22 normal fatty acids (C22:0), C23:0, C24:0. Namely, in these two series of sulfatides, either fatty acids or sphingoids were hydroxylated, and chain lengths of these components were exactly the same, consequently resulting in a similar polarity of ceramide moieties in these sulfatide species. These results demonstrated diversities of sulfatide molecular species, not only with respect to sugar moieties but also to ceramide moieties, which are probably important for specific effective functions in particular microenvironments such as lipid membrane microdomains.

Animals↗

ING3 promotes UV-induced apoptosis via Fas/caspase-8 pathway in melanoma cells.

The novel ING tumor-suppressor family proteins (ING1-5) have been discovered during the past decade and are recognized as the regulators of transcription, cell cycle checkpoints, DNA repair, apoptosis, cellular senescence, angiogenesis, and nuclear phosphoinositide signaling. ING proteins contain a few conserved domains, including plant homeodomain motif, nuclear localization signal, and potential chromatin regulatory domain, suggesting that the ING family proteins may share common biological functions. ING3 has been shown to modulate p53-mediated transcription, cell cycle control, and apoptosis, possibly by modulating the NuA4 complex histone acetyltransferase activity. Because ING1b and ING2 have been shown to be involved in cellular stress responses such as nucleotide excision repair and apoptosis after UV irradiation, we investigated whether ING3 also mediated UV-induced apoptosis. We found that ING3 expression was rapidly induced by UV irradiation at both mRNA and protein levels. Using the stable clones of melanoma cells overexpressing ING3, we showed that overexpression of ING3 significantly promoted UV-induced apoptosis. Unlike its homologues ING1b and ING2, ING3-increased apoptosis was independent of functional p53. Furthermore, ING3 did not affect the expression of mitochondrial proteins but increased the cleavage of Bid and caspases-8, -9, and -3. Moreover, ING3-mediated apoptosis was blocked by inhibition of caspase-8 or Fas activation. In addition, ING3 up-regulated Fas expression at both mRNA and protein levels. Knock down of ING3 decreased UV-induced apoptosis remarkably. These data indicate that ING3 plays an important role in cellular response to UV irradiation by enhancing UV-induced apoptosis through the activation of Fas/caspase-8 pathway.

Apoptosis↗