Tannic acid as a biphasic modulator of tau protein liquid-liquid phase separation.

Tannic acid (TA) is a natural polyphenol that shows great potential in the field of biomedicine due to its anti-inflammatory, anti-oxidant, anti-bacterial, anti-tumor, anti-virus, and neuroprotective activities. Recent studies have revealed that liquid-liquid phase separation (LLPS) is closely associated with protein aggregation. Therefore, modulating LLPS offers new insights into the treatment of neurodegenerative diseases. In this study, we investigated the influence of TA on the LLPS of the Alzheimer's-related protein tau and the underlying mechanism. Our findings indicate that TA affects the LLPS of tau in a biphasic manner, with initial promotion and subsequent suppression as the TA to tau molar ratio increases. TA modulates tau phase separation through a combination of hydrophobic interactions and hydrogen bonds. The balance between TA-tau and tau-tau interactions is found to be relevant to the material properties of TA-induced tau condensates. We further illustrate that the modulatory activity of TA in phase separation is highly dependent on the target proteins. These findings enhance our understanding of the forces driving tau LLPS under different conditions, and may facilitate the identification and optimization of compounds that can rationally modulate protein phase transition in the future.

Encapsulation of luteolin by self-assembled Rha/SSPS/SPI nano complexes: Characterization, stability, and gastrointestinal digestion in vitro.

Luteolin has anti-inflammatory, antioxidant, and anti-tumor functions, but its poor water solubility and stability limit its applications in foods as a functional component. In this study, the nanocomposites loading luteolin (Lut) with soybean protein isolate (SPI), soluble soybean polysaccharide (SSPS) and/or rhamnolipid (Rha) were prepared by layer-by-layer shelf assembly method, and their properties were also evaluated. The results showed that Rha/SPI/Lut had the smallest particle size (206.24 nm) and highest loading ratio (8.03 µg/mg) while Rha/SSPS/SPI/Lut had the highest encapsulation efficiency (82.45 %). Rha interacted with SPI through hydrophobic interactions as the main driving force, while SSPS attached to SPI with only hydrogen bonding. Furthermore, the synergistic effect between Rha and SSPS was observed in Rha/SSPS/SPI/Lut complex, in consequence, it had the best thermal and storage stability, and the slowest release in gastrointestinal digestion. Thus, this approach provided an alternative way for the application of luteolin in functional foods.

Effect of γ-oryzanol/ß-sitosterol-based oleogels on the physicochemical and gel properties of Nemipterus virgatus myofibrillar protein.

BACKGROUND: The effect of oleogels prepared with peanut oil and different concentrations of γ-oryzanol and ß-sitosterol mixture (γ/ß; 20, 40, 60, 80 and 100 g kg-1) on the physicochemical and gel properties of myofibrillar protein (MP) was investigated. RESULTS: The solubility and average particle size of MP first decreased and then increased with increasing γ/ß concentration. Peanut oil or oleogels could induce the exposure of hydrophobic amino acids and the unfolding of MP, thus significantly increasing the surface hydrophobicity, sulfhydryl content and absolute value of zeta potential, which reached maximum values when the γ/ß concentration was 60 g kg-1 (P < 0.05). The addition of peanut oil decreased the gel strength and water holding capacity of MP gel. However, oleogels prepared with 60 g kg-1 γ/ß could significantly increase the hydrophobic interactions and disulfide bond content of MP gel (P < 0.05), which promoted the crosslinking and aggregation of MP, enhancing the gel properties. Peanut oil had no significant influence on the secondary structure of MP, while oleogels promoted the transition of MP conformation from α-helix to ß-sheet structure. The results of light microscopy and confocal laser scanning microscopy indicated that oleogels prepared with 60 g kg-1 γ/ß filled in the pores of MP gel network to form denser and more uniform structure. CONCLUSION: Oleogels prepared with 60 g kg-1 γ/ß could effectively improve the quality of MP gel and have promising application prospects in surimi products. © 2024 Society of Chemical Industry.

The cryptic metabolites and anti-phytopathogenic activities from Nigrospora lacticolonia and Penicillium rubens uncovered by the synergism with host Paris polyphylla, monoculture, and co-culture.

The synergism of host Paris polyphylla medium, the monoculture, and the coculture led to seventeen new metabolites, including eight sesquiterpenes, 1-7 having uncommon structural motifs compared to similar caryophyllene derivatives, 8 with an unprecedented bicyclic framework, and three xyloketals (13-15) with unprecedented frameworks from Nigrospora lacticolonia; one polyketide, 17 with novel bicyclo [2.2.2] undecane skeleton, and five polyketide-terpenoid hybrids, 20 (one novel sulfated), 21-24 from Penicillium rubens. The structures were determined mainly by the NMR, HRESIMS, ECD calculation, and single-crystal X-ray diffraction. Nine cryptic compounds (2-4, 5, 12-15, 17) were produced by the inductions of host medium and the coculture. The compounds 13 from N. lacticolonia, 24-26, 28, 29, and 31 from P. rubens indicated significant antiphytopathogenic activities against N. lacticolonia with MICs at 2-4 µg/mL. Moreover, compounds 22-26, 28, 29, and 31 from P. rubens showed antifungal activities against P. rubens with MICs at 2-4 µg/mL. The synergistic effects of host medium and the coculture can induce the structural diversity of metabolites.

Effect of starch and peanut oil on physicochemical and gel properties of myofibrillar protein: Amylose content and addition form.

Starch and peanut oil (PO) were widely used to improve the gel properties of surimi, however, the impact mechanism of addition forms on the denaturation and aggregation behavior of myofibrillar protein (MP) is not clear. Therefore, the effect of starch, PO, starch/PO mixture, and starch-based emulsion on the physicochemical and gel properties of MP was investigated. The results showed that amylose could accelerate the aggregation of MP, while amylopectin was conducive to the improvement of gel properties. The addition of PO, starch/PO mixture, or starch-based emulsion increased the turbidity, solubility, sulfhydryl content of MP, and improved the gel strength, whiteness, and texture of MP gel. However, compared with starch/PO mixture group, the gel strength of MP with waxy, normal and high amylose corn starch-based emulsion increased by 22.68 %, 10.27 %, and 32.89 %, respectively. The MP containing emulsion had higher storage modulus than MP with starch/PO mixture under the same amylose content. CLSM results indicated that the oil droplets aggregated in PO or starch/PO mixture group, while emulsified oil droplets filled the protein gel network more homogeneously. Therefore, the addition of starch and PO in the form of emulsion could effectively play the filling role to improve the gel properties of MP.

Development of Pan-Anti-SARS-CoV-2 Agents through Allosteric Inhibition of nsp14/nsp10 Complex.

SARS-CoV-2 nsp14 functions both as an exoribonuclease (ExoN) together with its critical cofactor nsp10 and as an S-adenosyl methionine-dependent (guanine-N7) methyltransferase (MTase), which makes it an attractive target for the development of pan-anti-SARS-CoV-2 drugs. Herein, we screened a panel of compounds (and drugs) and found that certain compounds, especially Bi(III)-based compounds, could allosterically inhibit both MTase and ExoN activities of nsp14 potently. We further demonstrated that Bi(III) binds to both nsp14 and nsp10, resulting in the release of Zn(II) ions from the enzymes as well as alternation of protein quaternary structures. The in vitro activities of the compounds were also validated in SARS-CoV-2-infected mammalian cells. Importantly, we showed that nsp14 serves as an authentic target of Bi(III)-based antivirals in SARS-CoV-2-infected mammalian cells by quantification of both the protein and inhibitor. This study highlights the importance of nsp14/nsp10 as a potential target for the development of pan-antivirals against SARS-CoV-2 infection.

TRAF2/3 deficient B cells resist DNA damage-induced apoptosis via NF-κB2/XIAP/cIAP2 axis and IAP antagonist sensitizes mutant lymphomas to chemotherapeutic drugs.

Deletion of TRAF2 or TRAF3 in B cells prolongs their survival. However, it remains unknown whether deletion of such factors affects B cells' ability to tolerate DNA damage, which can be induced by chemotherapeutics and cause apoptosis. Genetic alterations of TRAF2 or TRAF3 are observed in subsets of human B-cell lymphomas and B cell-specific deletion of TRAF3 led to lymphoma development in aged mice. However, it remains unknown whether double deficiency of TRAF2 and TRAF3 accelerates B-cell lymphomagenesis. Here, we showed that B cell-specific TRAF2/3 double deficient (B-TRAF2/3-DKO) B cells were remarkably more resistant to DNA damage-induced apoptosis via upregulating cIAP2 and XIAP, which in turn attenuates caspase-3 activation. Mechanistically, resistance to DNA damage-induced apoptosis required NF-κB2, which effects by upregulating XIAP and cIAP2 transcription. B-TRAF2/3-DKO mice exhibited a shorter lifespan and succumbed to splenomegaly and lymphadenopathy. Unexpectedly, the incidence of B-cell lymphoma development in B-TRAF2/3-DKO mice was relatively rare (∼10%). Sequencing B cell receptor repertoire of diseased B cells revealed that TRAF2/3 deficiency caused abnormal oligoclonal or clonal expansion of B cells. While a fraction of mutant B cells (25-43%) from aged diseased mice harbored recurrent chromosomal translocations, primary B cells isolated from young B-TRAF2/3-DKO mice had no detectable chromosomal alterations, suggesting that TRAF2/3 deficiency per se does not cause evident genomic instability in B cells. Chemo-resistant TRAF3-deficient B-cell lymphomas were sensitized to chemotherapeutic drugs by blocking IAP activity using IAP antagonist. We conclude that double deficiency of TRAF2 and TRAF3 does not accelerate B-cell lymphomagenesis. Our studies provide insight into mechanisms regulating DNA damage-induced apoptosis and may help develop effective therapies targeting mutant B-cell lymphomas using IAP antagonist.

Protective effect and mechanism of Lycium ruthenicum polyphenols against acrylamide-induced neurotoxicity.

This study aimed to investigate the potential neuroprotective effects of Lycium ruthenicum polyphenols (LRP) against acrylamide (ACR)-induced neurotoxicity and the mechanism of action in vitro and in vivo. LRP treatment significantly attenuated ACR-induced cytotoxicity in SH-SY5Y cells in a dose-dependent manner. LRP treatment increased the nuclear factor erythroid-2-related factor 2 (Nrf2) protein and subsequent activation of downstream proteins in SH-SY5Y cells. LRP treatment down-regulated the expression of relevant apoptotic proteins, including JNK, P-JNK, P38, P-P38, and caspase 3 in ACR-induced cells. In vivo, LRP improved exploratory and locomotor deficits in ACR-induced rats. LRP activated the Nrf2 pathway in the striatum and substantia nigra. LRP treatment attenuated striatal ROS levels and increased GSH and SOD in ACR-induced rats. Immunohistochemistry, western blot, and ELISA revealed a significant increase in tyrosine hydroxylase (TH) neurons and dopamine and its metabolites in the striatum and substantia nigra under the protective effect of LRP. Therefore, LRP can be a protective agent against ACR-induced brain damage.

(-)-Epigallocatechin-3-gallate, a Polyphenol from Green Tea, Regulates the Liquid-Liquid Phase Separation of Alzheimer's-Related Protein Tau.

The microtubule-associated protein tau is involved in Alzheimer's disease and other tauopathies. Recently, tau has been shown to undergo liquid-liquid phase separation (LLPS), which is implicated in the physiological function and pathological aggregation of tau. In this report, we demonstrate that the green tea polyphenol (-)-epigallocatechin-3-gallate (EGCG) promotes the formation of liquid tau droplets at neutral pH by creating a network of hydrophobic interactions and hydrogen bonds, mainly with the proline-rich domain of tau. We further show that EGCG oxidation, tau phosphorylation, and the chemical structure of the polyphenol influence the efficacy of EGCG in facilitating tau LLPS. Complementary to the inhibitory activity of EGCG in tau fibrillization, our findings provide novel insights into the biological activity of EGCG and offer new clues for future studies on the molecular mechanism by which EGCG alleviates neurodegenerative diseases.

The antifeedant and antifungal cryptic metabolites isolated from tobacco endophytes induced by host medium and coculture.

Four new cryptic metabolites including one fumagillol derivative (2), one cyclohexenone derivative (4), one 10-membered lactone (5), and one natural 4-epi-brefeldin C (8), along with seven known compounds were found from isogenesis endophytes Aspergillus fumigatus, Penicillium janthinellum, Nigrospora sp., and Stagonosporopsis sp. induced by host Nicotiana tabacum medium and co-culture. The structures were determined mainly by spectroscopic methods, including extensive 1D, 2D NMR, MS techniques, ECD calculation, and Mosher's method. Compound 2 possessed a novel 1, 3-dioxetane residue and cyclohexane-containing terpenoid skeleton. Compounds 2, 4-7 and 10 showed significant antifungal activities against the plant pathogen Nigrospora sp. with MICs of 1 µg/mL. 2, 4, 5-7, and 10 indicated antifungal activities against Penicillium janthinellum, Aspergillus fumigatus, Phomopsis sp., and Alternaria sp. with MICs ≤8 µg/mL. Compounds 2, 6-8, and 10 (50 µg/cm2) and microbial fermentation extracts (100 µg/cm2) showed antifeedant activities against silkworms with feeding deterrence indices of 21-100%.

Protective Effect of Lycium ruthenicum Polyphenols on Oxidative Stress against Acrylamide Induced Liver Injury in Rats.

Acrylamide (ACR) is formed during tobacco and carbohydrate-rich food heating and is widely applied in many industries, with a range of toxic effects. The antioxidant properties of Lycium ruthenicum polyphenols (LRP) have been established before. This study aimed to research the protective effect of LRP against ACR-induced liver injury in SD rats. Rats were divided into six groups: Control, ACR (40 mg/kg/day, i.g.), LRP (50, 100, and 200 mg/kg/day, i.g.) plus ACR, and LRP groups. After 19 days, we evaluated oxidative status and mitochondrial functions in the rat's liver. The results showed that glutathione (GSH) and superoxide dismutase (SOD) levels increased after LRP pretreatment. In contrast, each intervention group reduced reactive oxygen species (ROS) and malondialdehyde (MDA) levels compared to the ACR group. Meanwhile, alanine aminotransferase (ALT), aspartate aminotransferase (AST), liver mitochondrial ATPase activity, mRNA expression of mitochondrial complex I, III, and expression of nuclear factor-erythroid 2-related factor 2 (Nrf2) and its downstream proteins were all increased. This study suggested that LRP could reduce ACR-induced liver injury through potent antioxidant activity. LRP is recommended as oxidative stress reliever against hepatotoxicity.

Circ_0014359 promotes oral squamous cell carcinoma progression by sponging miR-149.

This study aimed to explore the role and mechanism of circ_0014359 in the OSCC. We firstly investigated the expression levels of circ_0014359 in OSCC tissues and cell lines. Then, the effects of knocking down circ_0014359 on cellular viability, apoptosis, migration, and invasion of OSCC cell lines were observed by cell counting kit-8 assay, flow cytometry, and transwell assay. Xenografts mouse model was established to explore the in vivo effect of circ_0014359 on the tumor volume and size of OSCC. We found that circ_0014359 was highly expressed in the OSCC tissues and cell lines compared to the normal controls (P<0.05). The expression of circ_0014359 was associated with the survival of patients (P<0.05). For the OSCC cell lines, circ_0014359 knock down induced apoptosis and inhibited migration, invasion, and epithelial-mesenchymal transition of OSCC cells (P<0.001). In vivo, silencing the circ_0014359 blocked the growth of OSCC tumors. The circ_0014359 can directly interact with the micro-RNA-149 (miR-149). Inhibition of miR-149 can rescue the inhibitory effects of circ_0014359 knock down on OSCC cells. The circ_0014359-miR-149 pathway may be a novel target for developing strategies for the diagnosis and treatment of OSCC.

Accessibility of ENaC extracellular domain central core residues.

The epithelial Na+ channel (ENaC)/degenerin family has a similar extracellular architecture, where specific regulatory factors interact and alter channel gating behavior. The extracellular palm domain serves as a key link to the channel pore. In this study, we used cysteine-scanning mutagenesis to assess the functional effects of Cys-modifying reagents on palm domain ß10 strand residues in mouse ENaC. Of the 13 ENaC α subunit mutants with Cys substitutions examined, only mutants at sites in the proximal region of ß10 exhibited changes in channel activity in response to methanethiosulfonate reagents. Additionally, Cys substitutions at three proximal sites of ß and γ subunit ß10 strands also rendered mutant channels methanethiosulfonate-responsive. Moreover, multiple Cys mutants were activated by low concentrations of thiophilic Cd2+. Using the Na+ self-inhibition response to assess ENaC gating behavior, we identified four α, two ß, and two γ subunit ß10 strand mutations that changed the Na+ self-inhibition response. Our results suggest that the proximal regions of ß10 strands in all three subunits are accessible to small aqueous compounds and Cd2+ and have a role in modulating ENaC gating. These results are consistent with a structural model of mouse ENaC that predicts the presence of aqueous tunnels adjacent to the proximal part of ß10 and with previously resolved structures of a related family member where palm domain structural transitions were observed with channels in an open or closed state.

Rare Metastasis to the Submandibular Gland in Oral Squamous Cell Carcinoma.

PURPOSE: In the current recommendation of neck dissection in oral squamous cell carcinoma (OSCC), the submandibular gland (SMG) should also be removed. This study aimed to investigate the incidence and the patterns of SMG involvement in OSCC patients. METHODS: Patients initially diagnosed with OSCC between January 2018 and October 2020 were included. The distribution of lymph nodes metastasis in level IB was analyzed. RESULTS: We included 145 patients who underwent primary surgery and neck dissection in this study. All patients had level IB lymph node dissection and simultaneous removal of the SMG. Of these patients, only one patient (0.7%) had involvement in SMG by directly infiltrating from the primary tumor. A total of 18 positive lymph nodes were found in level IB in 16 patients, and no positive lymph nodes were located in the SMG. There were 6 lymph nodes located in the lateral part of the SMG and 12 lymph nodes located in the anterior of the SMG. Patients with tumors located in the buccal mucosa and N3 stage were the independent predictive factors associated with level IB nodal metastasis. CONCLUSION: Involvement of SMG in OSCC is quite rare. Preservation of the SMG during neck dissection in selected patients with OSCC seems to be feasible and oncologically safe.

LncRNA GACAT1 targeting miRNA-149 regulates the molecular mechanism of proliferation, apoptosis and autophagy of oral squamous cell carcinoma cells.

To explore the effects of lncRNA GACAT1/miR-149 molecular axis on the proliferation, apoptosis, migration and autophagy of oral squamous cell carcinoma (OSCC) cells, and to explore its molecular mechanism. The expressions of lncRNA GACAT1 and miR-149 in tissues and cell lines of patients with OSCC were detected by qRT-PCR. Si-control, GACAT1-siRNA, inhibitor NC and miR-149 inhibitors were transfected into OSCC cells separately or in combination with Lipofectamine 2000. The binding sites between lncRNA GACAT1 and miR-149 were predicted using the miRanda website, and the targeting relationship was verified by dual-luciferase assay. The expression of lncRNA XIST and miR-149 was detected by qRT-PCR. CCK-8 assay was used to detect cell activity. Cell cycle distribution and apoptosis were detected by flow cytometry. Cell migration ability was detected by Transwell assay. The expression of migration and autophagy-related proteins was detected by western blot. LncRNA GACAT1 was highly expressed in cancer tissues and cell lines of OSCC patients (P < 0.01), while miR-149 was low expressed (P < 0.01). LncRNA GACAT1 binds to miR-149 targeting. The down-regulation of lncRNA GACAT1 inhibited the proliferation and migration of OSCC cells and promoted apoptosis and autophagy (P < 0.01). The transfection of miR-149 inhibitor had the opposite effect. Knockdown of lncRNA GACAT1 and transfection with miR-149 inhibitor reversed the effect of GACAT1 silencing on OSCC cells. Inhibition of lncRNA GACAT1 can inhibit the proliferation and migration of OSCC cells, promote apoptosis and autophagy, and the mechanism may be related to the targeting of miR-149.

VEGF gene transfection restores the angiogenesis of oral submucous fibrosis in mice.

BACKGROUND: To explore the effectiveness of adenovirus-enhanced green fluorescent protein-vascular endothelial growth factor165 (AD-EGFP-VEGF165) transfection on fibroblasts from mice, and we assessed whether VEGF165 restores the angiogenesis of oral submucous fibrosis (OSF) in mice. METHODS: AD-EGFP-VEGF165 and AD-EGFP were transfected into fibroblasts from mouse buccal tissues in vitro. The expression of VEGF before and after transfection was detected by RT-qPCR and ELISA in each group of fibroblasts. Fifteen OSF mice (pre-experimental construction) were randomly divided into 3 groups, and equal amounts of AD-EGFP-VEGF165 virus, AD-EGFP virus, and saline were injected into the buccal submucosal tissue of OSF mice. The expression of VEGF and local tissue angiogenesis were observed and measured in each group of animals. RESULTS: The Ad-EGFP-VEGF165-transfected fibroblasts increased human and mouse VEGF expression compared to the Ad-EGFP group and control group (P<0.05). The buccal submucosal tissue of mice was injected with Ad-EGFP-VEGF165 after the 6th day, and the expression of VEGF was effectively expressed in AD-EGFP-VEGF165 group (P<0.05), while no positive expression observed in other groups. and the number of microvessels in the AD-EGFP-VEGF165 group increased significantly compared to the other groups (P<0.05). CONCLUSIONS: Ad-EGFP-VEGF165 can be successfully transfected into fibroblasts from mice, and restored the angiogenesis of OSF in mice.

[A new lignan from Euscaphis konishii].

The chemical constituents from the extract of the twigs of Euscaphis konishii with anti-hepatoma activity were investigated, twelve compounds by repeated chromatography with silica gel, Sephadex LH-20 and preparative-HPLC. The structures of the chemical components were elucidated by spectroscopy methods, as konilignan(1),(7R, 8S)-dihydrodehydrodico-niferylalcohol-9-O-ß-D-glucopyranoside(2),illiciumlignan B(3),threo-1-(4-hydroxy-3-methoxyphenyl)-2-[4-(3-hydroxypropyl)-2-methoxyphenoxy]-1,3-panediol(4),erythro-1-(4-hydroxy-3-methoxyphenyl)-2-[4-(3-hydroxypropyl)-2-methoxyphenoxy]-1,3-panediol(5), matairesinol(6), wikstromol(7), isolariciresinol(8),(+)-lyoniresinol(9), 4-ketopinoresinol(10), syringaresin(11), and vladinol D(12). Among them, compound 1 is a new lignan. Compounds 10 and 12 had moderate inhibitory activity on HepG2 cells, with IC_(50) values of 107.12 µmol·L~(-1) and 183.56 µmol·L~(-1), respectively.

Hositisines A and B, new alkaloids from the stems of Ormosia hosiei Hemsl. et Wils.

Two new alkaloids, named hositisines A (1) and B (2), with two known alkaloids (3 and 4) were isolated from the stems of Ormosia hosiei Hemsl. et Wils. Their structures were confirmed by UV, HRESIMS, NMR spectra. The absolute configurations of 1 and 2 were determined by quantum ECD calculation and ECD, respectively. Compounds 1-3 could significantly reduce the LDH release at the concentration 50 µM, which showed they could strongly protect the PC12 cells exposed to oxygen and glucose deprivation/reoxygenation (OGD/R) injury.

LncRNA HOTAIR Promotes Proliferation of Malignant Melanoma Cells through NF-Ï°B Pathway.

BACKGROUND: To study the effects of long non-coding ribonucleic acid (lncRNA) HOX transcript antisense intergenic RNA (HOTAIR) on the proliferation and apoptosis of malignant melanoma cells, and to explore its specific regulatory mechanism through the nuclear factor-kappa B (NF-Ï°B) signaling pathway. METHODS: LncRNA HOTAIR small-interfering RNAs (siRNAs) were designed and synthesized, and the effects of si-HOTAIR transfection on the proliferation and apoptosis of malignant melanoma cells were detected via cell counting kit-8 (CCK-8) assay, 4',6-diamidino-2-phenylindole (DAPI) staining assay and flow cytometry, respectively. The gene expressions were determined using quantitative reverse transcription-polymerase chain reaction (qRT-PCR), the changes in NF-Ï°B pathway-related proteins and apoptosis-associated proteins after interference in lncRNA HOTAIR were detected via Western blotting, and the level of NF-Ï°B in each group was determined via ELISA. RESULTS: The results of CCK-8 assay revealed that the cell proliferation rate significantly declined gradually in si-HOTAIR group compared with that in si-NC group and control group (P<0.05). The results of Western blotting and ELISA showed that the activity of NF-Ï°B in si-HOTAIR group was weakened (P<0.05), suggesting that down-regulation of HOTAIR can suppress the activity of NF-Ï°B. Compared with si-NC group and control group, si-HOTAIR group had remarkably increased gene and protein expressions of pro-apoptotic Bax, and remarkably decreased gene and protein expressions of anti-apoptotic Bcl-2 (P<0.05), demonstrating that down-regulation of HOTAIR can promote apoptosis. CONCLUSION: Down-regulation of lncRNA HOTAIR can inhibit the proliferation and promote the apoptosis of malignant melanoma cells and suppress the NF-Ï°B pathway.

The role of glucose-6-phosphate dehydrogenase in reactive oxygen species metabolism in apple exocarp induced by acibenzolar-S-methyl.

Apple exocarp was used to investigate the effect of acibenzolar-S-methyl (ASM) and dehydroepiandrosterone (DHEA) treatments on reaction oxygen species (ROS) metabolism. The results indicated that ASM enhanced the hydrogen peroxide (H2O2) content, the activities of superoxide dismutase (SOD), catalase (CAT), peroxidase (POD), ascorbate peroxidase (APX), monodehydroascorbate reductase (MDHAR), glutathione reductase (GR) and glucose-6-phosphate dehydrogenase (G6PDH). ASM also increased the contents of ascorbic acid (AsA), reduced glutathione (GSH) and nicotinamide ademine dinucleotidephosphate (NADPH), MdSOD and MdAPX expression, but decreased MdMDHAR and dehydroascorbate reductase (MdDHAR) expression. DHEA suppressed H2O2 accumulation and POD, APX, MDHAR, G6PDH activities, but increased SOD, CAT and GR activities compared to the control. ASM and DHEA treatments suppressed the contents of AsA, GSH and NADPH, and expression of MdSOD, MdAPX and MdMDHAR. These results suggest that DHEA treatment prevented ROS metabolism induced by ASM which showed the important role of G6PDH in maintaining redox homeostasis in apple exocarp.