Novel Gene Clusters for Natural Product Synthesis Are Abundant in the Mangrove Swamp Microbiome.

Natural microbial communities produce a diverse array of secondary metabolites with ecologically and biotechnologically relevant activities. Some of them have been used clinically as drugs, and their production pathways have been identified in a few culturable microorganisms. However, since the vast majority of microorganisms in nature have not been cultured, identifying the synthetic pathways of these metabolites and tracking their hosts remain a challenge. The microbial biosynthetic potential of mangrove swamps remains largely unknown. Here, we examined the diversity and novelty of biosynthetic gene clusters in dominant microbial populations in mangrove wetlands by mining 809 newly reconstructed draft genomes and probing the activities and products of these clusters by using metatranscriptomic and metabolomic techniques. A total of 3,740 biosynthetic gene clusters were identified from these genomes, including 1,065 polyketide and nonribosomal peptide gene clusters, 86% of which showed no similarity to known clusters in the Minimum Information about a Biosynthetic Gene Cluster (MIBiG) repository. Of these gene clusters, 59% were harbored by new species or lineages of Desulfobacterota-related phyla and Chloroflexota, whose members are highly abundant in mangrove wetlands and for which few synthetic natural products have been reported. Metatranscriptomics revealed that most of the identified gene clusters were active in field and microcosm samples. Untargeted metabolomics was also used to identify metabolites from the sediment enrichments, and 98% of the mass spectra generated were unrecognizable, further supporting the novelty of these biosynthetic gene clusters. Our study taps into a corner of the microbial metabolite reservoir in mangrove swamps, providing clues for the discovery of new compounds with valuable activities. IMPORTANCE At present, the majority of known clinical drugs originated from cultivated species of a few bacterial lineages. It is vital for the development of new pharmaceuticals to explore the biosynthetic potential of naturally uncultivable microorganisms using new techniques. Based on the large numbers of genomes reconstructed from mangrove wetlands, we identified abundant and diverse biosynthetic gene clusters in previously unsuspected phylogenetic groups. These gene clusters exhibited a variety of organizational architectures, especially for nonribosomal peptide synthetase (NRPS) and polyketide synthase (PKS), implying the presence of new compounds with valuable activities in the mangrove swamp microbiome.

Construction of a xylose metabolic pathway in Trichosporonoides oedocephalis ATCC 16958 for the production of erythritol and xylitol.

PURPOSE: Erythritol is a valuable compound as sweetener and chemical material however cannot be fermented from the abundant substrate xylose. METHODS: The strain Trichosporonoides oedocephalis ATCC 16958 was employed to produce polyols including xylitol and erythritol by metabolic engineering approaches. RESULTS: The introduction of a substrate-specific ribose-5-phosphate isomerase endowed T. oedocephalis with xylose-assimilation activity to produce xylitol, and eliminated glycerol production simultaneously. A more value-added product, erythritol was produced by further introducing a homologous xylulose kinase. The carbon flux was redirected from xylitol to erythritol by adding high osmotic pressure. The production of erythritol was improved to 46.5 g/L in flasks by fermentation adjustment, and the process was scaled up in a 5-L fermentor, with a 40 g/L erythritol production after 120 h, and a time-space yield of 0.56 g/L/h. CONCLUSION: This study demonstrated the potential of T. oedocephalis in the synthesis of multiple useful products from xylose.

Biogas slurry recirculation regulates food waste fermentation: Effects and mechanisms.

Regularly adding biogas slurry into fermentation reactors is an effective way to enhance hydrogen or methane production. However, how this method affects the production of valuable organic acids and alcohols is still being determined. This study investigated the effects of different addition ratios on semi-continuous fermentation reactors using food waste as a substrate. The results showed that an addition ratio of 0.2 increased lactic acid production by 30% with a yield of 0.38 ± 0.01 g/g VS, while a ratio of 0.4 resulted in mixed acid fermentation dominated by n-butyric acid (0.07 ± 0.01 g/g VS) and n-caproic acid (0.06 ± 0.00 g/g VS). The introduction of Bifidobacteriaceae by biogas slurry played a crucial role in increasing lactic acid production. In contrast, exclusive medium-chain fatty acid producers enhanced the synthesis of caproic acid and heptanoic acid via the reverse ß-oxidation pathway. Mechanism analyses suggested that microbial community structure and activity, substrate hydrolysis, and cell membrane transport system and structure changed to varying degrees after adding biogas slurry.

Enhanced methane production from the co-digestion of food waste and thermally hydrolyzed sludge filtrate.

Although many technologies can be applied to sewage sludge (SS) and food waste (FW) treatment, high investment and operational costs, high land occupation, and the "not-in-my-backyard" effect pose many challenges in practice. Thus, it is important to develop and utilize low-carbon or negative-carbon technologies to tackle the carbon problem. This paper proposes a method of anaerobic co-digestion of FW and SS, thermally hydrolyzed sludge (THS), or THS filtrate (THF) to enhance their methane potential. Compared to the co-digestion of SS with FW, the methane yield of the co-digestion of THS and FW was 9.7-69.7% higher, and that of the co-digestion of THF and FW was 11.1-101.1% higher. The synergistic effect was weakened with the addition of THS but enhanced with the addition of THF, potentially owing to the change in humic substances. Filtration removed most humic acids (HAs) from THS but retained fulvic acids (FAs) in THF. Moreover, THF produced 71.4% of the methane yield of THS, although only 25% of the organic matter permeated from THS to THF. This indicated that hardly biodegradable substances remained in the dewatering cake and were removed from anaerobic digestion systems. The results indicate that the co-digestion of THF and FW is an effective way to enhance methane production.

Lactic acid production from mesophilic and thermophilic fermentation of food waste at different pH.

It is promising to recover lactic acid (LA) from fermentation of food waste (FW). In this study, pH and temperatures were investigated comprehensively to find their effects on LA fermentation, and microbial analyses were used to take insight to the variation of LA production. The results showed that mesophilic fermentation benefited hydrolysis and acidification, leading to a high yield of LA, while thermophilic conditions restricted other producers at low pH, leading to a high purity of LA. Lactobacillus amylolyticus was the main LA producer under thermophilic conditions, but Thermoanaerobacterium thermosaccharolyticum boomed at pH 5.0-6.0 and it converted LA partly to butyric acid. Simultaneously, Bacillus coagulans also increased and improved the optical purity (OP) of L-LA. From a series of this study, an operational condition of pH 5.5 and temperature of 52 °C would be potentially suitable for lactate fermentation of FW with high purity of 89%, while a stable LA production with an OP of 68% was achieved at 55 °C and pH 6.0.

RNAi-microsponges form through self-assembly of the organic and inorganic products of transcription.

Inorganic nanostructures have been used extensively to package nucleic acids into forms useful for therapeutic applications. Here we report that the two products of transcription, RNA and inorganic pyrophosphate, can self-assemble to form composite microsponge structures composed of nanocrystalline magnesium pyrophosphate sheets (Mg2P2O7•3.5H2O) with RNA adsorbed to their surfaces. The microsponge particles contain high loadings of RNA (15-21 wt.%) that are protected from degradation and can be obtained through a rolling circle mechanism as large concatemers capable of mediating RNAi. The morphology of the RNAi microsponges is influenced by the time-course of the transcription reaction and interactions between RNA and the inorganic phase. Previous work demonstrated that polycations can be used to condense RNAi microsponges into nanoparticles capable of efficient transfection with low toxicity. Our new findings suggest that the formation of these nanoparticles is mediated by the gradual dissolution of magnesium pyrophosphate that occurs in the presence of polycations. The simple one-pot approach for assembling RNAi microsponges along with their unique properties could make them useful for RNA-based therapeutics.

Interaction of human arylamine N-acetyltransferase 1 with different nanomaterials.

Humans are exposed to nanoparticles in the environment as well as those in nanomaterials developed for biomedical applications. However, the safety and biologic effects of many nanoparticles remain to be elucidated. Over the past decade, our understanding of the interaction of proteins with various nanomaterials has grown. The protein corona can determine not only how nanoparticles interact with cells but also their biologic effects and toxicity. In this study, we describe the effects that several different classes of nanoparticles exert on the enzymatic activity of the cytosolic protein human arylamine N-acetyltransferase 1 (NAT1), a drug-metabolizing enzyme widely distributed in the body that is also responsible for the activation and detoxification of known carcinogens. We investigated three metal oxides (zinc oxide, titanium dioxide, and silicon dioxide), two synthetic clay nanoparticles (layered double hydroxide and layered silicate nanoparticles), and a self-assembling thermo-responsive polymeric nanoparticle that differ in size and surface characteristics. We found that the different nanoparticles induced very different responses, ranging from inhibition to marked enhancement of enzyme activity. The layered silicates did not directly inactivate NAT1, but was found to enhance substrate-dependent inhibition. These differing effects demonstrate the multiplicity of nanoparticle-protein interactions and suggest that enzyme activity may be compromised in organs exposed to nanoparticles, such as the lungs or reticulo-endothelial system.

PEG-polypeptide block copolymers as pH-responsive endosome-solubilizing drug nanocarriers.

Herein we report the potential of click chemistry-modified polypeptide-based block copolymers for the facile fabrication of pH-sensitive nanoscale drug delivery systems. PEG-polypeptide copolymers with pendant amine chains were synthesized by combining N-carboxyanhydride-based ring-opening polymerization with post-functionalization using azide-alkyne cycloaddition. The synthesized block copolymers contain a polypeptide block with amine-functional side groups and were found to self-assemble into stable polymersomes and disassemble in a pH-responsive manner under a range of biologically relevant conditions. The self-assembly of these block copolymers yields nanometer-scale vesicular structures that are able to encapsulate hydrophilic cytotoxic agents like doxorubicin at physiological pH but that fall apart spontaneously at endosomal pH levels after cellular uptake. When drug-encapsulated copolymer assemblies were delivered systemically, significant levels of tumor accumulation were achieved, with efficacy against the triple-negative breast cancer cell line, MDA-MB-468, and suppression of tumor growth in an in vivo mouse model.

Material flow analysis of an upgraded anaerobic digestion treatment plant with separated utilization of carbon and nitrogen of food waste.

Anaerobic digestion of food waste can recover carbon in the form of biogas, while the high concentration of ammonia nitrogen in the digestion effluent becomes troublesome. Therefore, some new treatment plants use three-phase centrifugation to separate homogenized food waste into nitrogen-rich fine slag for insect cultivation and carbon-rich liquid for anaerobic digestion. To analyze the effects of the carbon-nitrogen separation, an upgraded plant's material and elementary flows were investigated. The three-phase separation process redistributed carbon and nitrogen, and the biogas slurry was the primary output. The principal endpoint for C was the crude oil, capturing 57.1 ±â€¯13.1 % of the total input; the find slag collected 48.3 ±â€¯6.9 % of the total N input, and the biogas slag accepted 52.9 ±â€¯4.4 % of the P input. The carbon-nitrogen separation strategy can improve digestion efficiency and increase treatment benefits significantly, marking a promising direction for future developments in food waste utilization.

Therapeutic potential of the medicinal mushroom Ganoderma lucidum against Alzheimer's disease.

Alzheimer's disease (AD) is a high-incidence neurodegenerative disorder, characterized by cognitive impairment, memory loss, and psychiatric abnormalities. Ganoderma lucidum is a famous medicinal fungus with a long history of dietary intake, containing various bioactive components, and have been documented to exhibit antioxidant, anti-inflammatory, anti-tumor, anti-aging, and immunomodulatory effects, among others. Recent studies have shown that G. lucidum and its components have promising therapeutic potential against AD from various aspects, which can delay the progression of AD, improve cognitive function and quality of life. The underlying mechanisms mainly include inhibiting tau hyperphosphorylation, inhibiting Aß formation, affecting activated microglia, regulating NF-κB/MAPK signalling pathway, inhibiting neuronal apoptosis, modulating immune system, and inhibiting acetylcholinesterase, etc. This paper systematically reviewed the relevant studies on the therapeutic potential of G. lucidum and its active components for treatment of AD, key points related with the mechanism studies and clinical trials have been discussed, and further perspectives have been proposed. Totally, as a natural medicinal mushroom, G. lucidum has the potential to be developed as effective adjuvant for AD treatment owing to its therapeutic efficacy against multiple pathogenesis of AD. Further mechanical investigation and clinical trials can help unlock the complete potential of G. lucidum as a therapeutic option for AD.

Modified Zhenwu Tang delays chronic renal failure progression by modulating oxidative stress and hypoxic responses in renal proximal tubular epithelial cells.

Background: Tubulointerstitial fibrosis (TIF) is a critical pathological feature of chronic renal failure (CRF), with oxidative stress (OS) and hypoxic responses in renal proximal tubular epithelial cells playing pivotal roles in disease progression. This study explores the effects of Modified Zhenwu Tang (MZWT) on these processes, aiming to uncover its potential mechanisms in slowing CRF progression. Methods: We used adenine (Ade) to induce CRF in rats, which were then treated with benazepril hydrochloride (Lotensin) and MZWT for 8 weeks. Assessments included liver and renal function, electrolytes, blood lipids, renal tissue pathology, OS levels, the hypoxia-inducible factor (HIF) pathway, inflammatory markers, and other relevant indicators. In vitro, human renal cortical proximal tubular epithelial cells were subjected to hypoxia and lipopolysaccharide for 72 h, with concurrent treatment using MZWT, FM19G11, and N-acetyl-l-cysteine. Measurements taken included reactive oxygen species (ROS), HIF pathway activity, inflammatory markers, and other relevant indicators. Results: Ade treatment induced significant disruptions in renal function, blood lipids, electrolytes, and tubulointerstitial architecture, alongside heightened OS, HIF pathway activation, and inflammatory responses in rats. In vivo, MZWT effectively ameliorated proteinuria, renal dysfunction, lipid and electrolyte imbalances, and renal tissue damage; it also suppressed OS, HIF pathway activation, epithelial-mesenchymal transition (EMT) in proximal tubular epithelial cells, and reduced the production of inflammatory cytokines and collagen fibers. In vitro findings demonstrated that MZWT decreased apoptosis, reduced ROS production, curbed OS, HIF pathway activation, and EMT in proximal tubular epithelial cells, and diminished the output of inflammatory cytokines and collagen. Conclusion: OS and hypoxic responses significantly contribute to TIF development. MZWT mitigates these responses in renal proximal tubular epithelial cells, thereby delaying the progression of CRF.

Natural chalcopyrite mitigates nitrous oxide emissions in sediment from coastal wetlands.

Coastal wetlands are one of the most important natural sources of nitrous oxide (N2O). Previous studies have shown that copper-containing chemicals are able to reduce N2O emissions from these ecosystems. However, these chemicals may harm organisms present in coastal waters and sediment, and disturb the ecological balance of these areas. Here, we first investigated the physiological characteristics and genetic potential of denitrifying bacteria isolated from coastal wetlands. Based on an isolated denitrifier carrying a complete denitrification pathway, we tested the effect of the natural mineral chalcopyrite on N2O production by the bacteria. The results demonstrated that chalcopyrite addition lowers N2O emissions from the bacteria while increasing its N2 production rate. Among the four denitrification genes of the isolate, only nosZ gene expression was significantly upregulated following the addition of 2 mg L-1 chalcopyrite. Furthermore, chalcopyrite was applied to coastal wetland sediments. The N2O flux was significantly reduced in 50-100 mg L-1 chalcopyrite-amended sets relative to the controls. Notably, the dissolved Cu concentration in chalcopyrite-amended sediment remained within the limit set by the National Sewage Treatment Discharge Standard. qPCR and metagenomic analysis revealed that the abundance of N2O-reducing bacteria with the nosZ or nirK + nosZ genotype increased significantly in the chalcopyrite-amended groups relative to the controls, suggesting their active involvement in the reduction of N2O emissions. Our findings offer valuable insights for the use of natural chalcopyrite in large-scale field applications to reduce N2O emissions.

Pentacyclic hemiacetal sterol with antifouling and cytotoxic activities from the soft coral Nephthea sp.

A novel unusual pentacyclic hemiacetal sterol nephthoacetal (1), was isolated from soft coral Nephthea sp. The structure of this sterol was inferred from its two acetyl derivatives (2) and (3), by means of spectroscopic methods, and quantum chemical calculations. Anti-fouling activity of compounds 1-3 against Bugula neritina larvae was evaluated, sterol (1) exhibited significant inhibitory effect with EC(50) value of 2.5 µg/mL, while having low toxicity with LC(50)>25.0 µg/mL. The in vitro cytotoxic activity of compounds 1-3 against HeLa cells was also evaluated, all of them exhibited moderate cytotoxicity with IC(50) values of 12.3 (1), 10.1 (2), and 19.6 µg/mL (3), respectively.

[Study on the secondary metabolites from marine sponge Phakellia fusca].

OBJECTIVE: To study the secondary metabolites from marine sponge Phakellia fusca. METHODS: The compounds were isolated by column chromatography over silica gel and purified by Sephadex LH-20 column chromategraphy and preparative TLC. The structures were elucidated by means of physiochemical properties and spectroscopic analysis. RESULTS: Ten compounds were separated and identified as: p-hydroxybenzoic acid (1), cetanic acid (2), batyl alcohol (3), cety ethers of glycerol (4), (E)-N-2-(1,3-dihydroxy octadecan-4-en)-hexade-camide (5), thymidine (6), cyclo-(L-Tyr-L-Pro) (7), phenyl acetylamine (8), uracil (9),4-hydroxybenzamide (10). CONCLUSION: Compound 5, 7 and 10 are isolated from Phakellia fusca for the first time.

A comprehensive review on the medicinal usage of Podocarpus species: Phytochemistry and pharmacology.

ETHNOPHARMACOLOGICAL RELEVANCE: Plants of the Podocarpus species belong to the Podocarpaceae family and are largely distributed in the southern hemisphere. Beside the commercially and ecologically valuable, plants of the Podocarpus species are also used in traditional medicines in some countries for treating asthma, fever, venereal diseases, eye diseases, etc. AIM OF THE STUDY: In recent decades, the identities and pharmacological activities of phytochemicals extracted from Podocarpus plants have been widely studied. However, there have been no comprehensive and systematic reviews. This article aims to systematically review the latest research on the putative mechanisms underlying pharmacological actions of phytochemicals from the Podocarpus species, as well as to lay a foundation for promoting the development of plant resources from this genus, further drug research, and product development. MATERIALS AND METHODS: A comprehensive search of PubMed, Google Scholar, Web of Science, Elsevier and CNKI databases was conducted using the keywords "Podocarpus", "traditional usage", "phytochemistry", "pharmacology", "nagilactone", etc. Related papers published among July 1964 to February 2023 were collected to summarize the research progress. All plant names were determined through the "The Plant List" (http://www.theplantlist.org/). RESULTS: To date, 262 chemical constituents have been isolated and identified from 26 Podocarpus plants; among these, norditerpene bilactone is the main pharmacologically active component. Norditerpene bilactones are reported to have anti-cancer, anti-inflammatory, antioxidant, antibacterial, anti-tyrosinase, neuroprotective, anti-plasmodial, anti-mutagenic, and anti-atherosclerotic properties as well as other pharmacological activities, which support its traditional uses. CONCLUSION: Extensive studies on phytochemistry and pharmacology of Podocarpus species lead to discovery of a series of hopeful leading compounds with unique chemical structure, especially the nor- and bis-norditerpenoid dilactones with four isoprene units. These compounds have been proved to possess various pharmacological activities. This review will provide a reference for further research and promote the idea of combining modern research with traditional medicinal applications of Podocarpus plants.

CS27109, A Selective Thyroid Hormone Receptor-ß Agonist Alleviates Metabolic-Associated Fatty Liver Disease in Murine Models.

Background/Aim: Thyroid hormone receptor-ß (THR-ß) agonists play crucial roles in dyslipidemia and metabolic associated fatty liver disease (MAFLD). We developed a novel oral and liver-targeted THR-ß agonist, CS27109, and evaluated its efficacy in the treatment of metabolic disorders. Materials and Methods: We evaluated in vitro and in vivo efficacy and/or safety of CS27109 along with MGL3196 (a phase III THR-ß agonist). Results: CS27109 showed pronounced activity and selectivity to THR-ß and favorable PK properties, which was equivalent to MGL3196. In the hamster model, animals treated with a high dose of CS27109 showed equivalent reductions in serum TC and LDL-c with groups treated with MGL3196. In the rat model, CS27109 and MGL3196 reduced serum ALT, TC, TG, LDL-c, liver weight ratio, and liver steatosis. CS27109 simultaneously decreased liver TG and TC, and MGL3196 additionally reduced AST. In the mouse model, CS27109 dose-dependently reduced serum AST, ALT, liver inflammation, and NAS score, and also downregulated TC, LDL-c, liver steatosis, and fibrosis, but not in a dose-dependent manner. MGL3196 revealed an equivalent effect with CS27109 in that model. CS27109 also exhibited tolerable toxicity to the heart. Conclusions: CS27109 shows comparative in vitro and in vivo efficacy with MGL3196, suggesting its potential therapeutic application in the treatment of MAFLD such as dyslipidemia and steatohepatitis.

Discovery of a novel, liver-targeted thyroid hormone receptor-ß agonist, CS271011, in the treatment of lipid metabolism disorders.

Introduction: Thyroid hormone receptor ß (THR-ß) plays a critical role in metabolism regulation and has become an attractive target for treating lipid metabolism disorders in recent years. Thus, in this study, we discovered CS271011, a novel THR-ß agonist, and assessed the safety and efficiency of CS271011 compared to MGL-3196 in vitro and in vivo. Methods: We conducted luciferase reporter gene assays to assess the activation of THR-ß and α in vitro. C57BL/6J mice were fed a high-fat diet for 12 weeks, CS271011 was administered by gavage at the dose of 1 mg/kg and 3 mg/kg, and MGL-3196 was administered at the dose of 3 mg/kg for 10 weeks. Body weight, food intake, serum and hepatic parameters, histological analysis, pharmacokinetic studies, RNA sequencing of the liver and heart, and expression of hepatic lipid-metabolic genes were determined to evaluate the safety and efficiency of CS271011. Results: Compared with MGL-3196, CS271011 showed higher THR-ß activation in vitro. In the diet-induced obesity mice model, CS271011 demonstrated favourable pharmacokinetic properties in mice and was enriched in the liver. Finally, CS271011 improved dyslipidaemia and reduced liver steatosis in the diet-induced obesity murine model. Mechanistically, CS271011 and MGL-3196 showed potent regulation of lipid metabolism-related genes. Conclusions: CS271011 is a potent and liver-targeted THR-ß agonist for treating lipid metabolism disorders.

Nano-silica anti-icing coatings for protecting wind-power turbine fan blades.

Wind power is a promising electricity source. Nevertheless, wind turbine blade icing can cause severe problems in turbine operation. In this study, SiO2 spherical nanoparticles (∼90 nm), produced by RF (radio frequency) plasma spheroidization, were mixed with E51, PDMS, and ethyl acetate, and sprayed on the surface of aluminum plates and regular power windmill fan blades which were already coated with polyurethane primer. XPS and IR spectroscopies revealed the development of SiC and SiPh (Ph = phenolic ring) bonds, whose formation should be favored by the ultrasound and curing processes at 50 °C. The integrity of the coating/substrate interface, whose strength is ascribed to hydrogen bonds, was maintained after 100 icing-melting cycles. The coatings display superhydrophobic behavior and excellent anti-icing performance, along with stability in abrasion, sunlight and self-cleaning ability towards solid pollutants.

DNA alterations of microsatellite DNA, p53, APC and K-ras in Chinese colorectal cancer patients.

BACKGROUND: Colorectal cancer is one of the most rapidly increasing cancers in the world, and accumulation of alterations in oncogenes, tumour suppressor genes and mismatch repair (MMR) genes contributes to colorectal tumorigenesis. Thus, we investigated the alterations of 14 microsatellite loci adjacent to MMR genes, p53, adenomatous polyposis coli (APC) and K-ras in 52 Chinese patients with colorectal cancer. MATERIALS AND METHODS: We performed fluorescent polymerase chain reaction and capillary electrophoresis to analyse microsatellite instability (MSI) and loss of heterozygosity (LOH) in microsatellite loci, which included a panel of nine dinucleotide repeats and the Bethesda consensus panel. Additionally, we screened for mutations in exons 4-9 of p53 and the mutation cluster region (MCR) in APC by DHPLC. Codons 12, 13 and 61 in K-ras were analysed using direct sequencing. All variations were confirmed using clone sequencing. RESULTS: The alteration frequency of microsatellite DNA was 55·8% (29/52). Among the microsatellites, five loci exhibited MSI and another nine loci exhibited LOH. The mutation rates of p53, APC and K-ras were 42·3%, 38·5% and 36·5%, respectively. All patients (n = 7) with liver metastasis had a mutation in p53, APC or K-ras. APC mutation was correlated with clinical stage and the presence of lymph node metastasis (P = 0·001 and P = 0·006, respectively). CONCLUSIONS> A total of 80·8% of Chinese patients with colorectal cancer show variations in microsatellite DNA, p53, APC or K-ras. It appears that these microsatellite DNA alterations could be a new biomarker for colorectal cancer.

Circular RNA circ_0008934 promotes hepatocellular carcinoma growth and metastasis through modulating miR-1305/TMTC3 axis.

Circular RNAs (circRNAs) play important roles in the progression of hepatocellular carcinoma (HCC). However, the exact function of circ_0008934 in HCC is unknown. Our study aimed to investigate the expression characteristics of circ_0008934 in HCC and its effects on the proliferation and metastasis of HCC, and to explore the potential mechanism. In this study, circ_0008934 expression was found to be significantly upregulated in HCC tissues and cell lines by qRT-PCR. High level of circ_0008934 is closely associated with higher serum AFP (P < 0.001), larger tumor diameter (P = 0.012), microvascular invasion (P = 0.008) and poorer prognosis (P = 0.007) of HCC patients. Functionally, knockdown of circ_0008934 inhibited HCC cell proliferation, invasion and migration in vitro and vivo. Mechanically, circ_0008934 was a sponge of miR-1305 to facilitate the TMTC3 expression, and the TMTC3 expression in HCC tissues was negatively associated with the survival of HCC patients. Furthermore, rescued assays revealed that the circ_0008934 facilitated HCC proliferation, invasion and migration by regulating miR-1305/ TMTC3 signaling pathways. Overall, these results demonstrate that downregulation of circ_0008934 repress HCC growth and metastasis by upregulating miR-1305 to inhibit TMTC3, suggesting circ_0008934/ miR-1305/ TMTC3 regulatory axis may be a possible novel therapeutic target for HCC.