High-molecular-weight Fucoidan exerts an immune-enhancing effect in RAW 264.7 cells and cyclophosphamide-induced immunosuppression rat by altering the gut microbiome.

High-molecular-weight fucoidan (Fucoidan P), sourced from Undaria pinnatifida exhibits several health benefits, including immunomodulation. However, the mechanisms underlying the immune-enhancing effects of Fucoidan P remain unclear. Here, we investigated the immune-enhancing effects and the potential mechanisms of Fucoidan P using RAW 264.

Tumor suppressor protein p53-mediated repression of human mitotic centromere-associated kinesin gene expression is exerted via down-regulation of Sp1 level.

The repressive role of p53 on the human mitotic centromere-associated kinesin (MCAK) core promoter from ‒266 to +54, relative to the transcription start site, has been determined. The MCAK mRNA and protein levels were 2.1- and 3.

Anti-inflammatory action of 2-carbomethoxy-2,3-epoxy-3-prenyl-1,4-naphthoquinone (CMEP-NQ) suppresses both the MyD88-dependent and TRIF-dependent pathways of TLR4 signaling in LPS-stimulated RAW264.7 cells.

Ethnopharmacological Relevance: The roots of Rubia cordifolia L. have been widely used as a traditional herbal medicine in Northeast Asia for treating inflammatory diseases.

Aim Of The Study: To elucidate the anti-inflammatory mechanism of 2-carbomethoxy-2,3-epoxy-3- prenyl-1,4-naphthoquinone (CMEP-NQ), purified from the roots of R.

Discovery and synthesis of novel allylthioaralkylthiopyridazines: their antiproliferative activity against MCF-7 and Hep3B cells.

A new series of 6-allylthio-3-aralkylthio-4,5-dimethylpyridazines 5a-5k and 1-allylthio-4-alkylthio-5,6,7,8-tetrahydrophthalazine 6a-6j was synthesized from maleic anhydride derivatives for development of new anticancer agents. The process involves the formation of pyridazine and phthalazine rings, dichlorination, allylthiolation, and aralkylthiolation. These new compounds showed antiproliferative activities against breast cancer (MCF-7) and hepatocarcinoma (Hep3B) cells in CCK-8 assays, and could be promising candidates for chemotherapy of carcinomas.

Proteasome inhibitor MG132-induced apoptosis via ER stress-mediated apoptotic pathway and its potentiation by protein tyrosine kinase p56lck in human Jurkat T cells.

Exposure of human Jurkat T cells to MG132 caused apoptosis along with upregulation of Grp78/BiP and CHOP/GADD153, activation of JNK and p38MAPK, activation of Bak, mitochondrial membrane potential (Δψm) loss, cytochrome c release, activation of caspase-12, -9, -3, -7, and -8, cleavage of Bid and PARP, and DNA fragmentation. However, these MG132-induced apoptotic events, with the exceptions of upregulation of Grp78/BiP and CHOP/GADD153 and activation of JNK and p38MAPK, were abrogated by overexpression of Bcl-xL. Pretreatment with the pan-caspase inhibitor z-VAD-fmk prevented MG132-induced apoptotic caspase cascade, but allowed upregulation of Grp78/BiP and CHOP/GADD153 levels, activation of JNK and p38MAPK, Δψm loss, and cleavage of procaspase-9 (47kDa) to active form (35kDa).

Mollugin induces apoptosis in human Jurkat T cells through endoplasmic reticulum stress-mediated activation of JNK and caspase-12 and subsequent activation of mitochondria-dependent caspase cascade regulated by Bcl-xL.

Exposure of Jurkat T cells to mollugin (15-30 microM), purified from the roots of Rubia cordifolia L., caused cytotoxicity and apoptotic DNA fragmentation along with mitochondrial membrane potential disruption, mitochondrial cytochrome c release, phosphorylation of c-Jun N-terminal kinase (JNK), activation of caspase-12, -9, -7, -3, and -8, cleavage of FLIP and Bid, and PARP degradation, without accompanying necrosis. While these mollugin-induced cytotoxicity and apoptotic events including activation of caspase-8 and mitochondria-dependent activation of caspase cascade were completely prevented by overexpression of Bcl-xL, the activation of JNK and caspase-12 was prevented to much lesser extent.

Protein tyrosine kinase p56lck-deficiency confers hypersusceptibility to rho-fluorophenylalanine (pFPhe)-induced apoptosis by augmenting mitochondrial apoptotic pathway in human Jurkat T cells.

Phenylalanine analog, rho-fluorophenylalanine (pFPhe)-mediated cytotoxicity and several apoptotic events including mitochondrial cytochrome c release, activation of caspase-9, -3, and -8, Bid cleavage, degradation of PARP and PLCgamma-1, and DNA fragmentation were more significant in p56(lck)-deficient Jurkat T cells (JCaM1.6) than in wild-type Jurkat T cells (E6.1).

17Alpha-estradiol arrests cell cycle progression at G2/M and induces apoptotic cell death in human acute leukemia Jurkat T cells.

A pharmacological dose (2.5-10 microM) of 17alpha-estradiol (17alpha-E(2)) exerted a cytotoxic effect on human leukemias Jurkat T and U937 cells, which was not suppressed by the estrogen receptor (ER) antagonist ICI 182,780. Along with cytotoxicity in Jurkat T cells, several apoptotic events including mitochondrial cytochrome c release, activation of caspase-9, -3, and -8, PARP degradation, and DNA fragmentation were induced.

Regulation of the human mitotic centromere-associated kinesin (MCAK) promoter by the transcription factors Sp1 and E2F1.

To understand transcriptional regulation of the human mitotic centromere-associated kinesin (MCAK) promoter, the 1,151-bp promoter region of the human MCAK gene in Jurkat T cells was cloned by polymerase chain reaction (PCR). Although a bioinformatic analysis of the promoter sequence predicted several putative transcription factor binding sites for E2F, Sp1, c-Myb, p53, p300, NF-1, AML-1a, Ap-1, E-box factor, and C/EBPalpha/beta with no consensus TATA-box motif, deletion constructs of the promoter region revealed that the core positive promoter activity resided at -266/-66, containing three GC-motifs for binding Sp1. Site-directed disruption and chromatin immunoprecipitation analysis indicated that Sp1-binding to the GC-motifs was crucial for promoter activation, but the E2F1-binding to the E2F-motif (-57/-50) was crucial for promoter repression.

Positive regulation of promoter activity of human 3-phosphoglycerate dehydrogenase (PHGDH) gene is mediated by transcription factors Sp1 and NF-Y.

The PHGDH gene encodes the 3-phosphoglycerate dehydrogenase that catalyzes the transition of 3-phosphoglycerate into 3-phosphohydroxy pyruvate for the phosphorylated pathway of serine biosynthesis. To understand transcriptional regulation of the human PHGDH promoter, a genomic clone containing the 5'-flanking region of the PHGDH gene was isolated from a human genomic library. The 1192-bp PHGDH promoter region was cloned by PCR using the genomic DNA isolated from the PHGDH genomic clone.

Cytotoxicity of diacetoxyscirpenol is associated with apoptosis by activation of caspase-8 and interruption of cell cycle progression by down-regulation of cdk4 and cyclin B1 in human Jurkat T cells.

To understand the mechanism underlying T-cell toxicity of diacetoxyscirpenol (DAS) from Fusarium sambucinum, its apoptogenic as well as growth retardation activity was investigated in human Jurkat T cells. Exposure to DAS (0.01-0.

Active and passive intranasal immunizations with streptococcal surface protein C5a peptidase prevent infection of murine nasal mucosa-associated lymphoid tissue, a functional homologue of human tonsils.

C5a peptidase, also called SCPA (surface-bound C5a peptidase), is a surface-bound protein on group A streptococci (GAS), etiologic agents for a variety of human diseases including pharyngitis, impetigo, toxic shock, and necrotizing fasciitis, as well as the postinfection sequelae rheumatic fever and rheumatic heart disease. This protein is highly conserved among different serotypes and is also expressed in human isolates of group B, C, and G streptococci. Human tonsils are the primary reservoirs for GAS, maintaining endemic disease across the globe.

The M protein is dispensable for maturation of streptococcal cysteine protease SpeB.

The streptococcal pyrogenic exotoxin B (SpeB) is an important virulence factor of group A streptococci (GAS) with cysteine protease activity. Maturation of SpeB to a proteolytically active form was suggested to be dependent on cell-wall-anchored M1 protein, the major surface protein of GAS (M. Collin and A.

Primary induction of CD4 T cell responses in nasal associated lymphoid tissue during group A streptococcal infection.

CD4 T cells are important for development of long-term immunity to bacterial infections. Here we describe construction of a group A streptococcus (GAS) strain that expresses the model ovalbumin epitope (OVA) on its surface, and the use of this strain in adoptive transfer experiments to study CD4 T cell response to bacterial infection in nasal-associated lymphoid tissue (NALT), which was previously shown to be a specific target for GAS colonization. The OVA(+) GAS, but not the wild-type strain was shown to activate CD4 T cells in an antigen-specific manner both in vitro and in vivo.

Nasal associated lymphoid tissue & M cells, a window to persistent streptococcal infections.

Background & Objectives: Intranasal infection of mice has been used as a model of streptococcal pharyngitis, as nasal associated lymphoid tissue (NALT) in this animal is structurally and functionally analogous to human tonsils. The present study was carried out to determine whether group A streptococci preferentially colonized or invaded NALT.

Methods: Lux(+) strain Sp3 was created and exponential phase bacteria were introduced intranasally into BALB/C female mice, total photon emission from selected areas was quantified, sections of NALT tissues were used for immunofluorescent staining and M cell staining.

Promotion of fibronectin independent invasion by C5a peptidase into epithelial cells in group A Streptococcus.

Background & Objectives: Group A Streptococcus, causative agent of several clinical manifestations codes for multiple protein invasins which help the bacterium to enter non-phagocytic cells. C5a peptidase (SCPA) is a surface protein conserved among different serotypes of M1 strain. The present study was taken up to study SCPA promoted fibronectin independent entry of GAS into epithelial cells.

Membranous cells in nasal-associated lymphoid tissue: a portal of entry for the respiratory mucosal pathogen group A streptococcus.

Human tonsils are suspected to be an antibiotic-impervious human reservoir for group A streptococcus. An intranasal infection model in mice and a bioluminescent-tagged strain were used to investigate this possibility. Viable streptococci were predominantly found both intra- and extracellularly in nasal-associated lymphoid tissue (NALT), a human tonsil homologue.

Modification of type IV pilus-associated epithelial cell adherence and multicellular behavior by the PilU protein of Neisseria gonorrhoeae.

Expression of type IV pili (Tfp) correlates with the ability of Neisseria gonorrhoeae to colonize the human host, as well as with adherence to human epithelial tissue, twitching motility, competence for natural transformation, and autoagglutination. N. gonorrhoeae PilF (required for Tfp biogenesis) and PilT (required for twitching motility and transformation) share significant identities with members of a family of putative ATPases involved in membrane trafficking of macromolecules.