Epithelial-Mesenchymal Transformation Promotes the Progression of Hepatocellular Carcinoma through NF-κB/MMP9 Axis.

BACKGROUND: Primary liver cancer (PHC) stands as one of the most prevalent malignant diseases in clinical settings. Studies have indicated that transcatheter arterial chemoembolization (TACE) treatment exhibits superior clinical outcomes, potentially increasing the complete necrosis rate in patients with PHC. A correlation exists between the clinical outcomes of TACE surgery and the process of epithelial-mesenchymal transition (EMT), yet the underlying mechanism remains a mystery. Hence, it is crucial to investigate the impact and mechanism of EMT on hepatocellular carcinoma (HCC). METHODS: Retrospectively, patients with advanced liver cancer who underwent TACE were selected and categorized into two groups based on the assessment of clinical efficacy: the effective group and the ineffective group. The expression levels of nuclear factor-kappa B (NF-κB), matrix metalloproteinase 9 (MMP9), Ki-67, B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X (Bax), Vimentin, E-cadherin, and N-cadherin in tumor tissues were evaluated using reverse transcription-polymerase chain reaction (RT-PCR). In vitro, Huh7 cells were cultured, and lentivirus infections were utilized to inhibit the overexpression of NF-κB and MMP9. The determination of EMT and cell viability was conducted through Cell Counting Kit-8 (CCK-8) assays, RT-PCR, and Western blot. RESULTS: Sixty patients diagnosed with advanced liver cancer were selected for the study. Based on their clinical outcomes, 30 patients with advanced hepatocellular carcinoma were categorized into the effective group, while the remaining 30 patients were categorized into the ineffective group. The results of the Western blot analysis indicated that, in comparison to the effective group, the expression levels of NF-κB, MMP9, Ki-67, Bcl-2, Vimentin, and N-cadherin were significantly higher in the tumor tissues of the ineffective group. Conversely, the expression of Bax and E-cadherin was notably lower in the effective group. Following the individual knockdown of NF-κB and MMP9, the cell experiments revealed a remarkable decrease in the expression levels of Ki-67, Bcl-2, Vimentin, and N-cadherin, whereas the expression of Bax and E-cadherin showed significant elevation (p < 0.05). Furthermore, there was a significant increase in cell viability and a decrease in cell apoptosis after the knockdown of NF-κB and MMP9. CONCLUSIONS: The NF-κB/MMP9 signaling axis serves as a pivotal regulator that fosters proliferation and impedes apoptosis in Huh7 cells by modulating the process of EMT.

A recognition of exosomes as regulators of epigenetic mechanisms in central nervous system diseases.

Exosomes, vesicular structures originating from cells, participate in the conveyance of proteins and nucleic acids. Presently, the centrality of epigenetic modifications in neurological disorders is widely acknowledged. Exosomes exert influence over various epigenetic phenomena, thereby modulating post-transcriptional regulatory processes contingent upon their constituent makeup. Consequently, the heightened attention directed toward exosomes as instigators of epigenetic alterations has burgeoned in recent years. Notably, exosomes serve as vehicles for delivering methyltransferases to recipient cells. More significantly, non-coding RNAs, particularly microRNAs (miRNAs), represent pivotal contents within exosomes, wielding the capacity to influence the expression of diverse factors within the cerebral milieu. The transfer of these exosomal contents amidst brain cells, encompassing neuronal cells and microglia, assumes a critical role in the genesis and progression of neurological disorders, also, this role is not limited to neurological disorders, it may deal with any human disease, such as cancer, and cardiovascular diseases. This review will concentrate on elucidating the regulation of exosome-induced epigenetic events and its subsequent ramifications for neurological diseases. A more profound comprehension of the involvement of exosome-mediated epigenetic regulation in neurological disorders contributes to a heightened awareness of the etiology and advancement of cerebral afflictions.

Influence of Dietary Phosphorus on the Growth, Feed Utilization, Proximate Composition, Intestinal Enzymes, and Oxidation Resistance of Sea Cucumber Apostichopus japonicus.

Six experimental diets (crude protein 12.58%, crude fat 1.93%, and total energy 10.72 kJ/kg) containing 0.24%, 0.37%, 0.51%, 0.62%, 0.77%, and 0.89% phosphorus were formulated to evaluate dietary phosphorus requirement for sea cucumber Apostichopus japonicus. The feeding trial was conducted in 18 fiberglass tanks (220 L) for 63 days. Each diet was randomly assigned to triplicate tanks of 50 sea cucumbers (9.99 g) and fed once daily. With the increase of dietary phosphorus level, weight gain (WG), specific growth rate (SGR), daily feed intake (DFI), feces production ratio, the activities of amylase, alkaline phosphatase, phosphofructokinase, succinate dehydrogenase, and glutathione peroxidase as well as the contents of glutathione and glutathione oxidized significantly increased and then decreased afterwards (P < 0.05). A. japonicus fed diet with 0.63%, 0.63%, and 0.55% dietary phosphorus was estimated to yield the highest WG (11.39 g), SGR (1.09%/d), and DFI (2.55%/d) according to the quadratic regression analysis of WG, SGR, and DFI against dietary phosphorus level, respectively. The apparent digestibility of dry material and energy followed an opposite tendency. Feed efficiency, the contents of whole-body phosphorus, initially increased and then plateaued, fitting piecewise-linear models with breakpoint at 0.57% and 0.55% dietary phosphorus. Daily phosphorus intake, pyruvate kinase activity, and the ratio of glutathione and glutathione oxidized increased (P < 0.05) but the apparent digestibility of phosphorus, the activities of alkaline protease, aspartate transaminase, and phosphoenolpyruvate carboxykinase decreased (P < 0.05), responding to the increasing dietary phosphorus. Considering the present results, the optimal dietary phosphorus for A. japonicus is 0.57-0.63%.

Sources, bioaccumulation, and toxicity mechanisms of cadmium in Chlamys farreri.

The Potentially toxic elements (PTEs) cadmium (Cd) is one of the most serious stressors polluting the marine environment. Marine bivalves have specific high enrichment capacity for Cd. Previous studies have investigated the tissue distribution changes and toxic effects of Cd in bivalves, but the sources of Cd enrichment, migration regulation during growth, and toxicity mechanisms in bivalves have not been fully explained. Here, we used stable-isotope labeling to investigate the contributions of Cd from different sources to scallop tissues. We sampled the entire growth cycle of Chlamys farreri, which is widely cultured in northern China, from juveniles to adult scallops. We found tissue variability in the bioconcentration-metabolism pattern of Cd in different bound states, with Cd in the aqueous accounting for a significant contribution. The accumulation pattern of Cd in all tissues during growth was more significant in the viscera and gills. Additionally, we combined a multi-omics approach to reveal a network of oxidative stress-induced toxicity mechanisms of Cd in scallops, identifying differentially expressed genes and proteins involved in metal ion binding, oxidative stress, energy metabolism, and apoptosis. Our findings have important implications for both ecotoxicology and aquaculture. They also provide new insights into marine environmental assessment and mariculture development.

Aptamer-mediated hollow MnO2 for targeting the delivery of sorafenib.

Sorafenib (SRF) presents undesirable effects in clinical treatment, due to the lack of targeting, poor water solubility, and obvious side effects. In this study, we constructed a novel nanodrug carrier system for accurate and efficient delivery of SRF, improving its therapeutic effects and achieving tumor-specific imaging. The hollow mesoporous MnO2 (H-MnO2) nanoparticles equipped with target substance aptamers (APT) on the surface were used to load SRF for the first time. The resulting H-MnO2-SRF-APT could specifically bound to glypican-3 (GPC3) receptors on the surface of hepatocellular carcinoma (HCC), rapidly undergoing subsequent degradation under decreased pH conditions in the tumor microenvironment (TME) and releasing the loaded SRF. In this process, Mn2+ ions were used for T1-weighted magnetic resonance imaging simultaneously. The in vitro cell experiments indicated that H-MnO2-SRF-APT showed much more effects on the inhibition in the proliferation of Huh7 and HepG2 HCC cells than that of the non-targeted H-MnO2-SRF and free SRF. Besides, the in vivo results further confirmed that H-MnO2-SRF-APT could effectively inhibit the growth of xenograft tumors Huh7 in the naked mouse with good biosafety. In conclusion, H-MnO2-SRF-APT could significantly enhance the therapeutic effect of SRF and is expected to be a new way of diagnosis and treatment of HCC.

Acidification of seawater attenuates the allelopathic effects of Ulva pertusa on Karenia mikimotoi.

Acidification of seawater resulting from absorption of excessive carbon dioxide from the atmosphere is posing a serious threat to marine ecosystem. In this study, we hypothesized that acidified seawater attenuates allelopathic effects of macroalgae on red tide algae because the increase of dissolved carbon dioxide benefits algal growth, and investigated the allelopathic effects of Ulva pertusa on Karenia mikimotoi in response to seawater acidification by determining cell density, photosynthetic pigment content, chlorophyll fluorescence parameters, and chloroplast structure of K. mikimotoi under U. pertusa stress in original (pH=8.2) and acidified (pH=7.8) seawater. U. pertusa inhibited the growth of K. mikimotoi in the original and acidizing seawater, and the inhibition rate was positively correlated with treatment time and concentration of U. pertusa. However, acidizing condition significantly weakened the inhibition degree of U. pertusa on K. mikimotoi (P < 0.05), with the inhibition rates decreased from 51.85 to 43.16% at 10 gFW/L U. pertusa for 96 h. U. pertusa reduced contents of chlorophyll a, chlorophyll c, and carotenoid, maximum photochemical quantum yield (Fv/Fm), actual quantum yield, maximum relative electron transfer efficiency (rETRmax) of PSII, real-time fluorescence value (F), and maximum fluorescence value (Fm') of PSII of K. mikimotoi under original and acidified conditions. And, the inhibition degree of U. pertusa under acidizing condition was significantly lower than that of original seawater group. Furthermore, the damage degree of chloroplast structure of K. mikimotoi under U. pertusa stress was more serious under original seawater condition. These results indicate that acidification of seawater attenuates the allelopathic effects of U. pertusa on K. mikimotoi.

Effects of Spartina alterniflora invasion on the community structure and diversity of wetland soil bacteria in the Yellow River Delta.

The exotic plant Spartina alterniflora is expanding rapidly along China's coast regions, seriously threatening native ecosystems. Soil bacteria are important for biogeochemical cycles, including those of carbon, nitrogen, and sulfur, in wetland ecosystems. There is growing evidence that microorganisms are important in case of plant invasion. In the present study, we studied the interlacing area of S. alterniflora and Suaeda heteroptera, selected soil of invaded and non-invaded regions and explored the effect of the composition and diversity of bacterial communities in coastal wetlands. The bacterial community composition of invasive and noninvasive areas was subjected to high-throughput sequencing. In the five areas tested, the main bacterial phyla were Proteobacteria, Bacteroides, and Acidobacteria; the richness of the bacterial community in the soil increased after S. alterniflora invasion, most changes occurred at the genus level. The relative abundances of Desulfobulbus and Sulfurovum were higher in invasive areas than in noninvaded areas. PCA, RDA, and LEfSe analyses found that the S. alterniflora invasion significantly influenced the bacterial community and physicochemical properties of wetland soil. In conclusion, soil microbial community composition was tightly associated with S. alterniflora invasion. This study provide an important scientific basis for further research on the invasion mechanism of S. alterniflora.

The complete mitochondrial genome of Tetragonia tetragonioides (Pall.) Kuntze and its phylogenetic implications.

The complete mitochondrial genome sequence of Tetragonia tetragonioides (Pall.) Kuntze was assembled and characterized in the present study. The mitochondrial genome was 347,227 bp in length and had a GC content of 43.84%, including 24 transfer RNA (tRNA) genes and three ribosomal RNA (rRNA) genes. Phylogenetic analysis showed that T. tetragonioides was close to and Sesuvium portulacastrum.

A fas apoptotic inhibitory molecule from Ruditapes philippinarum: Investigation on molecular characterization and functional analysis.

In the present study, a fas apoptotic inhibitory molecule (FAIM) was identified from Ruditapes philippinarum (designated as RpFAIM). Multiple alignments and phylogenetic analysis strongly suggested that RpFAIM was a new member of the FAIMs family. The RpFAIM transcripts were constitutively expressed in a wide range of tissues, and dominantly expressed in hemocytes. After V. anguillarum or M. luteus challenge, the expression level of RpFAIM transcripts was significantly induced and reached the maximum level at 6 h and 24 h, respectively. Knockdown of RpFAIM down-regulated the transcript levels of NF-κB signaling genes (e.g. RpIKK, RpIκB, RpNF-κB). The results were roughly similar to those under bacterial stimulation. Moreover, RpFAIM primarily localized in the cell cytoplasm, and its over-expression inhibited the apoptosis of HeLa cells. These results revealed that RpFAIM perhaps regulated the NF-κB signaling pathways positively, which provided a better understanding of RpFAIM in innate immunity.

The complete plastid genome of a marine microalgae Cryptophyceae sp. CCMP2293 (Cryptophyta).

In this study, we present the complete plastid genome of Cryptophyceae sp. CCMP2293. The circular genome is 139,208 bp in length and contains 142 protein-coding genes (PCGs), 30 transfer RNA (tRNA) genes, 6 ribosome RNA (rRNA) genes, and 1 transfer-messenger RNA (tmRNA) gene. The overall nucleotide composition is: 33.6% A, 32.5% T, 16.8% C, and 17.1% G with a total A + T content of 66.1%. The phylogenetic tree was constructed to explore the taxonomic status of Cryptophyceae sp. CCMP2293, which is closely related to G. theta and R. salina.

Microalgal Microscale Model for Microalgal Growth Inhibition Evaluation of Marine Natural Products.

Marine organisms especially sessile invertebrates, such as soft corals, gorgonians and sponges, can survive in the competitive environment mainly relying on their second metabolites with chemoecological effects including allelopathy and algal growth inhibition. It is well known that the microscale models are urgently needed in marine chemoecology assessment to evaluate the algal growth inhibition activity of trace quantity natural products. In this work, a microalgal growth inhibition model was established for microalgal inhibition evaluation of marine natural products with 96-well microplate by automatic fluorescence observation using microplate reader. Subsequently, this model was applied to bioassay-guided isolation and preliminary bioactivity screening of the secondary metabolites from soft corals, gorgonians, sponges and their symbiotic microbes collected from the South China Sea. As a result, fifteen compounds (1‒15) were found to exhibit microalgal growth inhibition activities against at least one of marine microalgae, Karenia mikimotoi, Isochrysis galbana, and Heterosigma akashiwo. Specifically, altersolanol C (13) demonstrated potent activity against K. mikimotoi with the 96h-EC50 value of 1.16 µg/mL, more than four times stronger than that of the positive control K2Cr2O7. It was suggested that the microalgal growth inhibition microscale model is suitable for bioassay-guided isolation and preliminary bioactivity screening of marine natural products.

Effect of CO2-induced seawater acidification on growth, photosynthesis and inorganic carbon acquisition of the harmful bloom-forming marine microalga, Karenia mikimotoi.

Karenia mikimotoi is a widespread, toxic and non-calcifying dinoflagellate, which can release and produce ichthyotoxins and hemolytic toxins affecting the food web within the area of its bloom. Shifts in the physiological characteristics of K. mikimotoi due to CO2-induced seawater acidification could alter the occurrence, severity and impacts of harmful algal blooms (HABs). Here, we investigated the effects of elevated pCO2 on the physiology of K. mikimotoi. Using semi-continuous cultures under controlled laboratory conditions, growth, photosynthesis and inorganic carbon acquisition were determined over 4-6 week incubations at ambient (390ppmv) and elevated pCO2 levels (1000 ppmv and 2000 ppmv). pH-drift and inhibitor-experiments suggested that K. mikimotoi was capable of acquiring HCO3-, and that the utilization of HCO3- was predominantly mediated by anion-exchange proteins, but that HCO3- dehydration catalyzed by external carbonic anhydrase (CAext) only played a minor role in K. mikimotoi. Even though down-regulated CO2 concentrating mechanisms (CCMs) and enhanced gross photosynthetic O2 evolution were observed under 1000 ppmv CO2 conditions, the saved energy did not stimulate growth of K. mikimotoi under 1000 ppmv CO2, probably due to the increased dark respiration. However, significantly higher growth and photosynthesis [in terms of photosynthetic oxygen evolution, effective quantum Yield (Yield), photosynthetic efficiency (α), light saturation point (Ek) and ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) activity] were observed under 2000 ppmv CO2 conditions. Furthermore, elevated pCO2 increased the photo-inhibition rate of photosystem II (ß) and non-photochemical quenching (NPQ) at high light. We suggest that the energy saved through the down-regulation of CCMs might lead to the additional light stress and photo-damage. Therefore, the response of this species to elevated CO2 conditions will be determined by more than regulation and efficiency of CCMs.