Project description:Periodontal ligament stem cell-derived exosomes (PDLSC-exosomes) exhibit promising therapeutic potential in cancer treatment. Here, we characterize PDLSC-exosomes and investigate their effects on colorectal (HT-29, HCT-116) and oral (SCC-25) cancer cell lines. Nanoparticle tracking analysis and transmission electron microscopy revealed exosome diameters ranging from 80-220 nm and typical cup-shaped morphology. Flow cytometry confirmed surface markers CD9, CD63, and CD81. PKH67-labeling demonstrated efficient exosome internalization by all three cell lines. PDLSC-exosomes significantly inhibited cancer cell growth and colony formation in a dose-dependent manner. Synergistic effects were observed when combined with oxaliplatin, enhancing growth inhibition, apoptosis induction, and motility reduction. Apoptotic assays revealed increased Bax and p53 gene expression and altered protein profiles, particularly those involved in apoptosis and immune signaling pathways. Proteomic analysis identified differentially expressed proteins linked to translational processes and vesicle fusion. This study highlights the synergistic effects of PDLSC-exosomes and oxaliplatin, providing novel insights into their potential as an adjunct therapy to enhance cancer cell sensitivity and apoptosis.
Project description:Reef-building corals live in a mutualistic relationship with photosynthetic algae (family Symbiodiniaceae) that usually provide the bulk of the energy required by the coral host. This relationship is very sensitive to temperature stress, with as little as 1°C increase above mean in sea surface temperatures (SSTs) often leading to the collapse of the association. The meta-stability of these associations has led to interest in the potential of more stress tolerant algae to supplement or substitute for the normal Symbiodiniaceae mutualists. In this respect, the apicomplexan-like microalga Chromera is of particular interest as it is considerably more temperature tolerant than are most members of the Symbiodiniaceae. Here we generated a de novo transcriptome for a Chromera strain isolated from a GBR coral (“GBR Chromera”) and compared to those of the reference strain of Chromera (“Sydney Chromera”), and to those of Symbiodiniaceae algae (Fugacium, Cladocopium and Breviolum), as well as the apicomplexan parasite, Plasmodium falciparum. By contrast with the Symbiodiniaceae, the two Chromera strains had a high level of sequence similarity evident by very low levels of divergence in orthologous genes. Although surveys of specific KEGG categories provided few general criteria by which true coral mutualists might be identified, they provide a molecular rationalization for the near ubiquitous association of Cladocopium strains with Indo-Pacific reef corals in general and with Acropora spp. in particular. In addition, HSP20 genes may underlie the higher thermal tolerance shown by Chromera compared to Symbiodiniaceae
Project description:Urea can serve as nitrogen source for coral holobionts and plays a cruscial role in coral calcification, although the degradation of urea by coral symbionts is not fully understood. In this study, we investigated the urea utilized pathway and the responses of the Symbiodiniaceae family to urea under high temperature conditions. Genome screening revealed that all Symbiodiniaceae species contain the urease (URE) and DUR2 subunit of urea amidolyase (UAD) system. However, only three speciesCladocopium goreaui, Cladopium c92, and Symbiodinium pilosum possess a complete UAD system, including both DUR1 and DUR2. Phylogentic analyses revealed that the UAD system in Symbiodiniaceae clusters more closely with symbiotic bacteria, indicating that horizontal gene transfer of UAD system has occured in coral symbionts. Physiology analysis showed that the symbiodiniacean species Cladocopium goreaui, which containing both URE and UAD, grew better under urea than ammonium conditions, as indicated by higher maximum specific growth rates. Furthermore, most genes of Symbiodiniaceae involved in urea utilization appeared to be stable under various conditions such as heat stress (HS), low light density, and nitrogen deficiency, wheras in ammonium and nitrate transporters were significantly regulated. These relatively stable molecular regulatory properties support sustained urea absorption by Symbiodiniaceae, as evidenced by an increase in δ15N2-urea absorption and the decreases in δ5N-NO3-, and δ15N-NH4+ from cultural environment to Symbiodiniaceae under HS conditions. Token together, this study reveals two distinct urea utilization systems in coral ecosystem and highlights the importance of the urea cycle in coral symbionts when facing fluctuating nitrogen environment in future warming ocean.
Project description:Our studies revealed a novel oncogenic function of LSD1 in driving PCa progression by activating MYC signaling and mediating CRPC SEs activities, cotargeting LSD1 and BRD4 achieved significant synergistic effects in repressing CRPC tumor growth
Project description:<p>As a well-known pseudo-persistent environmental pollutant, oxybenzone (BP-3) and its related organic ultraviolet (UV) filters have been verified to directly contribute to the increasing mortality rate of coral reefs. Previous studies have revealed the potential role of symbiotic Symbiodiniaceae in protecting corals from the toxic effects of UV filters. However, the detailed protection mechanism(s) have not been explained. Here, the impacts of BP-3 on the symbiotic Symbiodiniaceae <em>Cladocopium goreaui</em> were explored. <em>C. goreaui</em> cells exhibited distinct cell growth at different BP-3 doses, with increasing growth at the lower concentration (2 mg/L) and rapid death at a higher concentration (20 mg/L). Furthermore, <em>C. goreaui</em> cells showed a significant BP-3 uptake at the lower BP-3 concentration. BP-3 absorbing cells exhibited elevated photosynthetic efficiency, and decreased cellular carbon and nitrogen contents. Besides, the derivatives of BP-3 and aromatic amino acid metabolism highly responded to BP-3 absorption and biodegradation. Our physiological and metabolic results reveal that the symbiotic Symbiodiniaceae could resist the toxicity of a range of BP-3 through promoting cell division, photosynthesis and reprogramming amino acid metabolism. This study provides novel insights into the influences of organic UV filters to coral reef ecosystems, which urgently needs increasing attention and management.</p>
Project description:We isolate the cultivable microbiome of a diatom and show that different bacteria have commensal, antagonistic, or synergistic effects on the diatom. One synergistic bacterium enhances growth of the diatom by production of auxin, a phytohormone. The diatom and its synergistic bacterium appear to use auxin and tryptophan as signaling molecules that drive nutrient exchange. Detection of auxin molecules and biosynthesis gene transcripts in the Pacific Ocean suggests that these interactions are widespread in marine ecosystems.
Project description:Our studies revealed a novel oncogenic function of LSD1 in driving PCa progression by activating MYC signaling and mediating CRPC SEs activities, cotargeting LSD1 and BRD4 achieved significant synergistic effects in repressing CRPC tumor growth
Project description:Our studies revealed a novel oncogenic function of LSD1 in driving PCa progression by activating MYC signaling and mediating CRPC SEs activities, cotargeting LSD1 and BRD4 achieved significant synergistic effects in repressing CRPC tumor growth
Project description:But4ManNAc - an analog of ManNAc, the committed precursor of sialic acid - decreases metastatic potential, inhibits growth, and triggers apoptosis in many cancer cells. The anti-tumor effects of But4ManNAc may result from a synergistic interaction between butyrate-induced changes in gene expression and ManNAc-induced altered sialylation. This experiment provides insight into synergistic interactions by identifying changes in gene expression specific to But4ManNAc and not shared with butyrate.