Sea cucumbers are predominant deposit feeders in benthic ecosystems, providing protective benefits to coral reefs by reducing disease prevalence. However, how they receive sufficient nutrition from seabed sediments remains poorly understood. Here, we investigate Holothuria leucospilota, an ecologically significant tropical sea cucumber, to elucidate digestive mechanisms underlying marine deposit-feeding. Genomic analysis reveals intriguing evolutionary adaptation characterized by an expansion of digestive carbohydrase genes and a contraction of digestive protease genes, suggesting specialization in digesting microalgae. Developmentally, two pivotal dietary shifts, namely, from endogenous nutrition to planktonic feeding, and from planktonic feeding to deposit feeding, induce changes in digestive tract enzyme profiles, with adults mainly expressing carbohydrases and lipases. A nuanced symbiotic relationship exists between gut microbiota and the host, namely, specific resident bacteria supply crucial enzymes for food digestion, while other bacteria are digested and provide assimilable nutrients. Our study further identifies Holothuroidea lineage-specific lysozymes that are restrictedly expressed in the intestines to support bacterial digestion. Overall, this work advances our knowledge of the evolutionary innovations in the sea cucumber digestive system which enable them to efficiently utilize nutrients from seabed sediments and promote food recycling within marine ecosystems.

Bladder cancer is a highly recurrent disease and a common cause of cancer-related deaths worldwide. Despite recent developments in diagnosis and therapy, the clinical outcome of bladder cancer remains poor; therefore, novel anti-bladder cancer drugs are urgently needed. Natural bioactive substances extracted from marine organisms such as sea cucumbers, scallops, and sea urchins are believed to have anti-cancer activity with high effectiveness and less toxicity. Frondoside A is a triterpenoid glycoside isolated from sea cucumber, Cucumaria frondosa. It has been demonstrated that Frondoside A exhibits anti-proliferative, anti-invasive, anti-angiogenic, anti-cancer, and potent immunomodulatory effects. In addition, CpG oligodeoxynucleotide (CpG-ODN) has also been shown to have potent anti-cancer effects in various tumors models, such as liver cancer, breast cancer, and bladder cancer. However, very few studies have investigated the effectiveness of Frondoside A against bladder cancer alone or in combination with CpG-ODN. In this study, we first investigated the individual effects of both Frondoside A and CpG-ODN and subsequently studied their combined effects on human bladder cancer cell viability, migration, apoptosis, and cell cycle in vitro, and on tumor growth in nude mice using human bladder cancer cell line UM-UC-3. To interrogate possible synergistic effects, combinations of different concentrations of the two drugs were used. Our data showed that Frondoside A decreased the viability of bladder cancer cells UM-UC-3 in a concentration-dependent manner, and its inhibitory effect on cell viability (2.5 μM) was superior to EPI (10 μM). We also showed that Frondoside A inhibited UM-UC-3 cell migration, affected the distribution of cell cycle and induced cell apoptosis in concentration-dependent manners, which effectively increased the sub-G1 (apoptotic) cell fraction. In addition, we also demonstrated that immunomodulator CpG-ODN could synergistically potentiate the inhibitory effects of Frondoside A on the proliferation and migration of human bladder cancer cell line UM-UC-3. In in vivo experiments, Frondoside A (800 μg/kg/day i.p. for 14 days) alone and in combination with CpG-ODN (1 mg/kg/dose i.p.) significantly decreased the growth of UM-UC-3 tumor xenografts, without any significant toxic side-effects; however, the chemotherapeutic agent EPI caused weight loss in nude mice. Taken together, these findings indicated that Frondoside A in combination with CpG-ODN is a promising therapeutic strategy for bladder cancer.

Cancer remains the primary cause of death worldwide. To develop less toxic anti-cancer drugs to relieve the suffering and improve the survival of cancer patients is the major focus in the anti-cancer field. To this end, marine creatures are being extensively studied for their anti-cancer effects, since extracts from at least 10% of the marine organisms have been shown to possess anti-tumor activities. As a classic Chinese traditional medicine, sea cucumbers and compounds extracted from the sea cucumbers, such as polysaccharides and saponins, have recently been shown to exhibit anti-cancer, anti-inflammatory, and anti-oxidant effects. Holothuria leucospilota (H. leucospilota) is a tropical edible sea cucumber species that has been successfully cultivated and farmed in large scales, providing a readily available source of raw materials to support the development of novel marine anti-cancer drugs. However, very few studies have so far been performed on the biological activities of H. leucospilota. In this study, we first investigated the anti-cancer effect of H. leucospilota protein on three cancer cell lines (i.e., HepG2, A549, Panc02) and three normal cell lines (NIH-3T3, HaCaT, 16HBE). Our data showed that H. leucospilota protein decreased the cell viabilities of HepG2, A549, HaCaT, 16HBE in a concentration-dependent manner, while Panc02 and NIH-3T3 in a time- and concentration-dependent manner. We also found that the inhibitory effect of H. leucospilota protein (≥10 μg/mL) on cell viability is near or even superior to EPI, a clinical chemotherapeutic agent. In addition, our data also demonstrated that H. leucospilota protein significantly affected the cell cycle and induced apoptosis in the three cancer cell lines investigated; in comparison, it showed no effects on the normal cell lines (i.e., NIH-3T3, HaCaT and 16HBE). Finally, our results also showed that H. leucospilota protein exhibited the excellent performance in inhibiting cell immigrations. In conclusion, H. leucospilota protein targeted the cancer cell cycles and induced cancer cell apoptosis; its superiority to inhibit cancer cell migration compared with EPI, shows the potential as a promising anti-cancer drug.

RNA viruses have a higher mutation rate than DNA viruses; however, RNA viruses are insufficiently studied outside disease settings. The International Committee on Taxonomy of Viruses (ICTV) is an organization set up by virologists to standardize virus classification. To better understand ICTV taxonomy and the characteristics and rules of different RNA virus families, we analyzed the 3,529 RNA viruses included in the 2020 ICTV report using five widely used metrics: length, host, GC content, number of predicted ORFs, and sequence similarity. The results show that host type has a significant influence on viral genome length and GC content. The genome lengths of virus members within the same genus are quite similar: 98.28% of the genome length differences within any particular genus are less than 20%. The species within those genera containing segmented viruses also have a similar length and number of segments. The number of predicted ORFs in the RNA viral genomes also shows a strong, statistically significant correlation with genome length. We suggest that due to the high mutation rate of RNA virus genomes, current RNA virus classification should mainly rely on protein similarities rather than nucleic acid similarities.

Purpose: Gut microbiota dysbiosis significantly impacts ulcerative colitis (UC) progression and exacerbation. Probiotics show promise in UC management. This study evaluated the effects of different doses of Bacillus pumilus LV149, an aquatic-derived probiotic, on gut injury repair in male C57BL/6 mice with dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) and investigated the underlying mechanisms.Methods: UC was induced by allowing mice free access to a 3% DSS solution for 7 days, with concurrent daily oral gavage of either a low (LV149-L, 1 × 10⁸ CFU/day/mouse) or high (LV149-H, 1 × 10⁹ CFU/day/mouse) dose of LV149. The effects were assessed through physiological parameters, intestinal barrier integrity, inflammation, gut microbiota composition, and transcriptomic changes.Results: LV149 significantly improved pathological symptoms, including weight loss and disease activity index (DAI), and reduced colon shortening in a dose-dependent manner and inflammatory damage. The intervention also restored gut barrier function by upregulating mucins, goblet cell counts, and tight junction proteins (ZO-1, occludin, and claudin-1) in colonic tissue, along with reducing serum lipopolysaccharide (LPS) levels. Notably, only the LV149-H significantly decreased the expression of pro-inflammatory cytokines TNF-α, IL-1β, and IL-6, while both doses increased the expression of the anti-inflammatory cytokine IL-10 in a dose-dependent in colonic tissue. LV149 further modulated the gut microbiota, increasing beneficial bacteria and reducing pathogenic populations. Transcriptomic analysis indicated that LV149-L may exert gut repair effects via the IL-17 signaling pathway, whereas LV149-H appears to act through the JAK-STAT signaling pathway.Conclusion: This study demonstrated that LV149, particularly at a higher dose, effectively mitigated DSS-induced colonic injury by modulating gut microbiota, enhancing gut barrier integrity, and reducing inflammation. The dose-dependent effects underscored LV149-H’s potential as a therapeutic agent for UC due to its stronger anti-inflammatory properties and gut-protective effects.

Background: Sea cucumbers exhibit a remarkable ability to regenerate damaged or lost tissues and organs, making them an outstanding model system for investigating processes and mechanisms of regeneration. They can also reproduce asexually by transverse fission, whereby the anterior and posterior bodies can regenerate independently. Despite the recent focus on intestinal regeneration, the molecular mechanisms underlying body wall regeneration in sea cucumbers still remain unclear. Results: In this study, transverse fission was induced in the tropical sea cucumber, Holothuria leucospilota, through constrainment using rubber bands. Histological examination revealed the degradation and loosening of collagen fibers on day-3, followed by increased density but disorganization of the connective tissue on day-7 of regeneration. An Illumina transcriptome analysis was performed on the H. leucospilota at 0-, 3- and 7-days after artificially induced fission. The differential expression genes were classified and enriched by GO terms and KEGG database, respectively. An upregulation of genes associated with extracellular matrix remodeling was observed, while a downregulation of pluripotency factors Myc, Klf2 and Oct1 was detected, although Sox2 showed an upregulation in expression. In addition, this study also identified progressively declining expression of transcription factors in the Wnt, Hippo, TGF-β, and MAPK signaling pathways. Moreover, changes in genes related to development, stress response, apoptosis, and cytoskeleton formation were observed. The localization of the related genes was further confirmed through in situ hybridization. Conclusion: The early regeneration of H. leucospilota body wall is associated with the degradation and subsequent reconstruction of the extracellular matrix. Pluripotency factors participate in the regenerative process. Multiple transcription factors involved in regulating cell proliferation were found to be gradually downregulated, indicating reduced cell proliferation. Moreover, genes related to development, stress response, apoptosis, and cell cytoskeleton formation were also involved in this process. Overall, this study provides new insights into the mechanisms of whole-body regeneration and uncover potential cross-species regenerative-related genes.