Correction: Nukulkit et al. Eight Indole Alkaloids from the Roots of Maerua siamensis and Their Nitric Oxide Inhibitory Effects. Molecules 2022, 27, 7558.

After a proofreading check, some experimental data were inconsistent with the supplementary information in the original publication [...].

Para rubber seed oil and its fatty acids alleviate photoaging and maintain cell homeostasis.

OBJECTIVE: Para rubber seed oil was indicated for skin dullness and hair loss in regard to its cutaneous beneficial fatty acids. Nonetheless, the oil's potency against photoaging remains unexplored. We proposed that para rubber seed oil could alleviate photoaging. METHODS: Para rubber seed oil was investigated in cocultures of human HaCaT cells and dermal fibroblasts (HDF). Photoaging protectant efficiency was monitored in terms of IL-6 and IL-8 as well as MMP-1 (collagenase) and MMP-9 (gelatinase) in a comparison with its fatty acid components. RESULTS: Para rubber seed oil standardized in fatty acids was indicated as the promising plant oil for photoaging treatment. Its photoprotection mechanism was demonstrated in the coculture system of keratinocyte and fibroblast cells for the first time. Where the oil and its fatty acid constituents (100 µg/mL) were indicated to be safe and efficiently protect the cocultures against UV damage. The oil significantly (p < 0.001) suppressed UV-induced IL-6, IL-8, MMP-1 and MMP-9 secretions. The revealed photoprotection proficiency was abided by its fatty acids, particularly the unsaturated C18 ones. CONCLUSION: The oil was indicated on its potential to maintain skin homeostasis and would alleviate senescence ageing in regard to its photoprotection abilities exhibited. Para rubber seed oil is warranted as a new generation of photoaging protectant agent with the profiled safety and efficacy demonstrated in the epidermal coculture system. The findings encourage the development of innovative anti-ageing products containing the oil, which is categorizable as a sustainable specialty material for photoaging treatment.

OBJECTIF: L'huile de graines de caoutchouc Para a été indiquée pour la peau terne et la perte de cheveux en ce qui concerne ses acides gras bénéfiques cutanés. Néanmoins, la propriété anti­photovieillissemen de l'huile reste inexplorée. Nous avons proposé que l'huile de graines de caoutchouc Para puisse atténuer le photovieillissement. MÉTHODES: L'huile de graines de caoutchouc Para a été étudiée dans des cocultures de cellules HaCaT humaines et de fibroblastes dermiques (HDF). L'efficacité de la protection contre le photovieillissement a été surveillée en termes d'IL­6 et d'IL­8, ainsi que de MMP­1 (collagénase) et de MMP­9 (gélatinase) en comparaison avec ses composants d'acides gras. RÉSULTATS: L'huile de graines de caoutchouc Para standardisée en acides gras a été indiquée comme huile végétale prometteuse pour le traitement du photovieillissement. Pour la première fois, son mécanisme de photoprotection a été démontré dans le système de coculture des cellules kératinocytaires et fibroblastiques. Où l'huile et ses composants d'acides gras (100 microgrammes/ml) ont été indiqués comme étant sûrs et protégeant efficacement les cocultures contre les dommages causés par les UV. L'huile a significativement (p < 0,001) supprimé les sécrétions d'IL­6, IL­8, MMP­1 et MMP­9 induites par les UV. La capacité de photoprotection révélée a été permise par ses acides gras, en particulier les acides gras insaturés C18. CONCLUSION: L'huile a été indiquée pour sa capacité de maintenir l'homéostasie de la peau et d'atténuer le vieillissement de sénescence en ce qui concerne ses capacités de photoprotection démontrées. L'huile de graines de caoutchouc Para est justifiée comme agent protecteur contre le photovieillissement de nouvelle génération avec la sécurité et l'efficacité décrites démontrées dans le système de coculture épidermique. Les résultats encouragent le développement de produits anti­vieillissement innovants contenant l'huile, qui est catégorisable comme un matériau spécialisé durable pour le traitement du photovieillissement.

Anti-skin ageing activities of rice (Oryza sativa) bran soft and hard waxes in cultured skin cells.

OBJECTIVE: Rice (Oryza sativa) bran waxes, the by-products of rice bran oil manufacturing, are widely used as inactive components in several preparations. Nevertheless, the function of rice bran waxes against skin ageing has never been reported. This study aimed to investigate thermal property and fatty acid profile of rice bran waxes, including rice bran soft (RBS) and hard (RBH) waxes, and the activities against skin ageing in cultured skin cells. METHODS: Thermal property and fatty acid profile of rice bran waxes were analysed by differential scanning calorimetry and gas chromatography-mass spectrometry, respectively. The cytotoxicity assay of waxes was performed in B16F10 melanoma cells, human skin fibroblasts and co-culture cells of HaCaT cells and human skin fibroblasts. The non-cytotoxic concentrations of waxes were evaluated for their activities against skin ageing, including melanogenesis assay, antioxidant activity, collagen content analysis, matrix metalloproteinase-1 and matrix metalloproteinase-2 inhibitory assay and anti-inflammatory activity. RESULTS: Thermal property indicated the endotherm peaks with melting temperatures at 40.89 ± 0.27°C and 69.64 ± 0.34°C for RBS and RBH, respectively. The main fatty acids in RBS were oleic (31.68 ± 0.75%) and linoleic acids (27.19 ± 0.40%), whereas those in RBH were palmitic (36.24 ± 1.08%) and stearic acids (35.21 ± 4.51%). The cytotoxicity assay in single cells and co-culture cells showed the non-cytotoxicity of RBS (0.0001-1 mg/mL) and RBH (0.0001-0.1 mg/mL). The anti-skin ageing activities of 1 mg/mL RBS and 0.1 mg/mL RBH included the melanogenesis inhibition by suppression of tyrosinase and tyrosinase-related protein-2 enzymes, the antioxidant activity by cellular protection against cell damage and cell death, the collagen stimulation, the matrix metalloproteinase-1 and matrix metalloproteinase-2 suppression and the anti-inflammation. CONCLUSIONS: The study results suggest that RBS and RBH can potentially be applied as the functional ingredients in formulations against skin ageing as well as provide the superior benefit on skin moisturization.

OBJECTIF: Les cires de son de riz (Oryza sativa) et les sous­produits de la fabrication de l'huile de son de riz sont largement utilisées comme composants inactifs dans plusieurs préparations. Néanmoins, l'effet des cires de son de riz contre le vieillissement de la peau n'a jamais été rapporté. Cette étude visait à étudier les propriétés thermiques et le profil d'acides gras des cires de son de riz, y compris les cires dures et douces de son de riz, et les activités contre le vieillissement de la peau dans les cellules cutanées en culture. MÉTHODES: La propriété thermique et le profil d'acides gras des cires de son de riz ont été analysés par calorimétrie différentielle à balayage et chromatographie en phase gazeuse couplée spectrométrie de masse, respectivement. Le dosage de la cytotoxicité des cires a été réalisé sur des cellules de mélanome B16F10, des fibroblastes de peau humaine, et des cellules de co­culture de cellules HaCaT et des fibroblastes de peau humaine. Les concentrations non cytotoxiques des cires ont été évaluées pour leurs activités contre le vieillissement de la peau, y compris l'analyse de la mélanogenèse, l'activité antioxydante, l'analyse de la teneur en collagène, le test de l'inhibiteur de la métalloprotéinase matricielle­1 et de la métalloprotéinase matricielle­2 et l'activité anti­inflammatoire. RÉSULTATS: La propriété thermique indiquait des pics endothermes avec des températures de fusion à 40,89 ± 0,27 °C et 69,64 ± 0,34 °C pour les cires dures et douces de son de riz, respectivement. Les principaux acides gras des cires douces de son de riz étaient des acides oléiques (31,68 ± 0,75 %) et des acides linoléiques (27,19 ± 0,40 %), tandis que ceux des cires dures de son de riz étaient des acides palmitiques (36,24 ± 1,08 %) et des acides stéariques (35,21 ± 4,51 %). Le dosage de la cytotoxicité dans les cellules individuelles et les cellules de co­culture a montré la non­cytotoxicité des cires douces de son de riz (0,0001 à 1 mg/ml) et des cires dures de son de riz (0,0001 à 0,1 mg/ml). Les activités antivieillissement de la peau de 1 mg/ml de cire douce de son de riz et de 0,1 mg/ml de cire dure de son de riz comprenaient l'inhibition de la mélanogenèse par suppression des enzymes de la tyrosinase et de la protéine liée à la tyrosinase 2, l'activité antioxydante par protection cellulaire contre les dommages et la mort cellulaires, la stimulation du collagène, la suppression de la métalloprotéinase matricielle­1 et la métalloprotéinase matricielle­2 et l'activité anti­inflammatoire. CONCLUSIONS: Les résultats de l'étude indiquent que les cires dures et douces de son de riz peuvent potentiellement être appliquées comme ingrédients fonctionnels dans des formulations contre le vieillissement de la peau et fournir un bénéfice supérieur en termes d'hydratation de la peau.

Computer-Aided Virtual Screening and In Vitro Validation of Biomimetic Tyrosinase Inhibitory Peptides from Abalone Peptidome.

Hyperpigmentation is a medical and cosmetic problem caused by an excess accumulation of melanin or the overexpression of the enzyme tyrosinase, leading to several skin disorders, i.e., freckles, melasma, and skin cancer. Tyrosinase is a key enzyme in melanogenesis and thus a target for reducing melanin production. Although abalone is a good source of bioactive peptides that have been used for several properties including depigmentation, the available information on the anti-tyrosinase property of abalone peptides remains insufficient. This study investigated the anti-tyrosinase properties of Haliotis diversicolor tyrosinase inhibitory peptides (hdTIPs) based on mushroom tyrosinase, cellular tyrosinase, and melanin content assays. The binding conformation between peptides and tyrosinase was also examined by molecular docking and dynamics study. KNN1 showed a high potent inhibitory effect on mushroom tyrosinase with an IC50 of 70.83 µM. Moreover, our selected hdTIPs could inhibit melanin production through the reductions in tyrosinase activity and reactive oxygen species (ROS) levels by enhancing the antioxidative enzymes. RF1 showed the highest activity on both cellular tyrosinase inhibition and ROS reduction. leading to the lower melanin content in B16F10 murine melanoma cells. Accordingly, it can be assumed that our selected peptides exhibited high potential in medical cosmetology applications.

Eight Indole Alkaloids from the Roots of Maerua siamensis and Their Nitric Oxide Inhibitory Effects.

Maerua siamensis (Capparaceae) roots are used for treating pain and inflammation in traditional Thai medicine. Eight new indole alkaloids, named maeruanitriles A and B, maeroximes A-C, and maeruabisindoles A-C, were isolated from them. Spectroscopic methods and computational analysis were applied to determine the structure of the isolated compounds. Maeroximes A-C possesses an unusual O-methyloxime moiety. The bisindole alkaloid maeruabisindoles A and B possess a rare azete ring, whereas maeruabisindole C is the first indolo[3,2-b]carbazole derivative found in this plant family. Five compounds [maeruanitriles A and B, maeroxime C, maeruabisindoles B, and C] displayed anti-inflammatory activity by inhibiting nitric oxide (NO) production in the lipopolysaccharide-induced RAW 264.7 cells. Maeruabisindole B was the most active inhibitor of NO production, with an IC50 of 31.1 ± 1.8 µM compared to indomethacin (IC50 = 150.0 ± 16.0 µM) as the positive control.

The Anticancer Effects of FDI-6, a FOXM1 Inhibitor, on Triple Negative Breast Cancer.

Triple-negative breast cancer (TNBC) presents an important clinical challenge, as it does not respond to endocrine therapies or other available targeting agents. FOXM1, an oncogenic transcriptional factor, has reported to be upregulated and associated with poor clinical outcomes in TNBC patients. In this study, we investigated the anti-cancer effects of FDI-6, a FOXM1 inhibitor, as well as its molecular mechanisms, in TNBC cells. Two TNBC cell lines, MDA-MB-231 and HS578T, were used in this study. The anti-cancer activities of FDI-6 were evaluated using various 2D cell culture assays, including Sulforhodamine B (SRB), wound healing, and transwell invasion assays together with 3D spheroid assays, mimicking real tumour structural properties. After treatment with FDI-6, the TNBC cells displayed a significant inhibition in cell proliferation, migration, and invasion. Increased apoptosis was also observed in the treated cells. In addition, we found that FDI-6 lead to the downregulation of FOXM1 and its key oncogenic targets, including CyclinB1, Snail, and Slug. Interestingly, we also found that the FDI-6/Doxorubicin combination significantly enhanced the cytotoxicity and apoptotic properties, suggesting that FDI-6 might improve chemotherapy treatment efficacy and reduce unwanted side effects. Altogether, FDI-6 exhibited promising anti-tumour activities and could be developed as a newly effective treatment for TNBC.

Abalone Collagen Extracts Potentiate Stem Cell Properties of Human Epidermal Keratinocytes.

Stem cell activities in human tissues are critical for tissue integrity and function. Maintaining keratinocyte stem cells (KSCs) stemness helps sustain healthy skin by supporting keratinocyte renewal, involving the formation of epidermal barriers. In this study, abalone collagen (AC) extracts with molecular weights of 3 kDa (AC 1) and 300 kDa (AC 2) were compared to the epidermal growth factor (EGF) for their effects on cell proliferation, cell migration (wound healing), spheroid formation, and the expression level of stem cell markers on human keratinocytes (HaCaT cells). Cell viability was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and cell proliferation was quantified by ATP and DNA content analysis and Sulforhodamine B (SRB) assays. Cell migration assay was determined using the scratch wound healing test. Spheroid formation was evaluated and the expression level of stem cell markers was investigated by western blot analysis. The results showed that AC 1 at the concentration of 100 µg/mL could stimulate HaCaT cell proliferation, migration, spheroid formation, and the expression level of stem cell markers (keratin 19, ß-catenin, ALDH1A1) compared to the control. In conclusion, a smaller molecular weight of abalone collagen extract exhibits a better effect on keratinocytes proliferation, migration, and stemness, which could be a potential active ingredient in cosmeceutical products.

Anticancer activity of arborinine from Glycosmis parva leaf extract in human cervical cancer cells.

Glycosmis parva is a small shrub found in Thailand. Ethyl acetate (EtOAc) extract from its leaves has been shown to exert anticancer effects in vitro; however, the compound responsible for this activity has not been isolated and characterized. In this study, we demonstrate that arborinine, a major acridone alkaloid in the EtOAc fraction, decreased proliferation and was strongly cytotoxic to HeLa cervical cancer cells without significantly affecting normal cells. The compound also inhibited tumor spheroid growth much more potently than chemotherapeutic drugs bleomycin, gemcitabine, and cisplatin. In addition, unlike cisplatin, arborinine activated caspase-dependent apoptosis without inducing DNA damage response. We further show that arborinine strongly suppressed cancer cell migration by downregulating expression of key regulators of epithelial-mesenchymal transition. Taken together, our data provide important insights into the molecular mechanism of arborinine's anticancer activity, supporting its potential use for treating cervical cancer.

Gonadotropin-releasing hormone-modified chitosan as a safe and efficient gene delivery vector for spermatogonia cells.

The use of male gonadal tissue as a site for the local delivery of DNA is an interesting concept. Previously, we reported synthesis, physiochemical and biological properties of gonadotropin-releasing hormone (GnRH)-conjugated chitosan as a carrier for DNA delivery to GnRH receptor-overexpressing cells. In this study, the application of modified chitosan as a potential vector for gene delivery to testicular cells was carried out. Transfection efficiency was investigated in mouse-derived spermatogonia cells (GC-1 cells) using green fluorescent protein as a reporter gene. GnRH-conjugated chitosan exhibited higher transfection activity and specificity compared to the unmodified chitosan. Furthermore, the GnRH-modified chitosan showed less cytotoxicity. In conclusion, we have developed and successfully tested the GnRH-modified chitosan for delivery of a transgene of interest to spermatogonia cells in vitro. Such vector could be useful in particular for testis-mediated gene transfer.

Wound healing and photoprotection properties of Acanthus ebracteatus Vahl. extracts standardized in verbascoside.

Acanthus spp. have been documented in traditional Thai herbal medicine and are applicable for the treatment of inflamed skin with wound healing property. Nonetheless, the scientific evidence necessary to prove the herb's doctrine has not yet been revealed. Verbascoside-rich extracts of the herbal medicine A. ebracteatus Vahl., were therefore prepared. The extracts and verbascoside were examined for their wound healing abilities using a scratch assay with fibroblasts. The anti-inflammatory effect suppressing MMP-9 was assessed in cocultures of keratinocyte (HaCaT cells) and fibroblasts. The extracts significantly improved wound healing compared with the control (p < 0.001). The wound healing effect of the extracts significantly (p < 0.01) increased with increasing verbascoside content. It should be noted that the extract was significantly (p < 0.05) better than verbascoside at the same test concentration. The extracts were capable of protecting cocultures of HaCaT cells and fibroblasts from photodamage. The extracts significantly (p < 0.001) suppressed cellular MMP-9 secretion following UV exposure, showing a better effect than that of verbascoside (p < 0.01). A. ebracteatus extract is promising for wound healing and photoprotection, and a prominent source of verbascoside. Verbascoside-rich A. ebracteatus could be utilized for the development of innovative skin-care products.

Recent insights into catechins-rich Assam tea extract for photoaging and senescent ageing.

Tea (Camellia spp.) is an important medicinal herb. C. sinensis var. sinensis is the most studied tea variety due to its more preferred flavor than C. sinensis var. assamica (Assam tea), the less economic importance with more bitter variety. A bitter taste highlights its potential as a candidate source for tea catechins, the health beneficial actives applicable for ageing treatment. Nonetheless, indicative data for tea on UV-induced and senescent ageing remain unclarified. Assam tea extract (ATE) was prepared and standardized in terms of TPC, TFC and TTC. EGCG was HPLC quantified as the prime ATE catechin. In vitro antioxidant activity of ATE was exhibited with ABTS, DPPH and FRAP assays. ATE's cellular antioxidant activity was indicated in HDFs at a stronger degree than ascorbic acid. The photoaging protection of ATE was evidenced in a coculture of HaCaT cells and HDFs. ATE markedly suppressed UV-induced IL-6, IL-8, MMP-1 and MMP-9 expressions. The proficiency of ATE targeting on senescent ageing was demonstrated in an ex vivo human skin model, where IL-6 and MMP-1 expressions were suppressed, whilst hyaluronic acid and collagen syntheses were promoted. ATE was chemically stabled as indicated by the catechin contents and color parameters following 6 months storage under conditions recommended for topical product. ATE enriched in catechins warrants its applicability as a new generation of photoaging protectant agent promising for the prevention and treatment for senescent ageing. The findings indicate the proficiency of ATE for innovative anti-ageing agent.

Assessing the Safety and Therapeutic Efficacy of Cannabidiol Lipid Nanoparticles in Alleviating Metabolic and Memory Impairments and Hippocampal Histopathological Changes in Diabetic Parkinson's Rats.

Diabetic Parkinson's disease (DP) is a progressive neurodegenerative disease with metabolic syndrome that is increasing worldwide. Emerging research suggests that cannabidiol (CBD) is a neuropharmacological compound that acts against this disease, especially CBD in nano-formulation. The safety of cannabidiol lipid nanoparticles (CBD-LNP) was evaluated by assessing in vitro cytotoxicity in neurons and therapeutic outcomes in a DP animal model, including metabolic parameters and histopathology. CBD-LNPs were fabricated by using a microfluidization technique and showed significantly lower cytotoxicity than the natural form of CBD. The DP rats were induced by streptozotocin followed by a 4-week injection of MPTP with a high-fat diet. Rats were treated orally with a vehicle, CBD, CBD-LNP, or levodopa for 4 weeks daily. As a result, vehicle-treated rats exhibited metabolic abnormalities, decreased striatal dopamine levels, and motor and memory deficits. CBD-LNP demonstrated reduced lipid profiles, enhanced insulin secretion, and restored dopamine levels compared to CBD in the natural form. CBD-LNP also had comparable efficacy to levodopa in ameliorating motor deficits and memory impairment in behavior tests. Interestingly, CBD-LNP presented migration of damaged neuronal cells in the hippocampus more than levodopa. These findings suggest that CBD-LNP holds promise as an intervention addressing both metabolic and neurodegenerative aspects of DP, offering a potential therapeutic strategy.

Skin Rejuvenation Efficacy and Safety Evaluation of Kaempferia parviflora Standardized Extract (BG100) in Human 3D Skin Models and Clinical Trial.

Polymethoxyflavones from Kaempferia parviflora rhizomes have been shown to effectively combat aging in skin cells and tissues by inhibiting senescence, reducing oxidative stress, and enhancing skin structure and function. This study assessed the anti-aging effects and safety of standardized K. parviflora extract (BG100), enriched with polymethoxyflavones including 5,7-dimethoxyflavone, 5,7,4'-trimethoxyflavone, 3,5,7,3',4'-pentamethoxyflavone, 3,5,7-trimethoxyflavone, and 3,5,7,4'-tetramethoxyflavone. We evaluated BG100's impact on skin rejuvenation and antioxidant properties using photoaged human 3D full-thickness skin models. The potential for skin irritation and sensitization was also assessed through studies on reconstructed human epidermis and clinical trials. Additionally, in vitro genotoxicity testing was performed following OECD guidelines. Results indicate that BG100 promotes collagen and hyaluronic acid production, reduces oxidative stress, and minimizes DNA damage in photoaged full-thickness 3D skin models. Furthermore, it exhibited non-irritating and non-sensitizing properties, as supported by tests on reconstructed human epidermis and clinical settings. BG100 also passed in vitro genotoxicity tests, adhering to OECD guidelines. These results underscore BG100's potential as a highly effective and safe, natural anti-aging agent, suitable for inclusion in cosmeceutical and nutraceutical products aimed at promoting skin rejuvenation.

Stress-induced changes in cognitive function and intestinal barrier integrity can be ameliorated by venlafaxine and synbiotic supplementations.

Stress profoundly impacts various aspects of both physical and psychological well-being. Our previous study demonstrated that venlafaxine (Vlx) and synbiotic (Syn) treatment attenuated learned fear-like behavior and recognition memory impairment in immobilized-stressed rats. In this study, we further investigated the physical, behavior, and cellular mechanisms underlying the effects of Syn and/or Vlx treatment on brain and intestinal functions in stressed rats. Adult male Wistar rats, aged 8 weeks old were subjected to 14 days of immobilization stress showed a decrease in body weight gain and food intake as well as an increase in water consumption, urinary corticosterone levels, and adrenal gland weight. Supplementation of Syn and/or Vlx in stressed rats resulted in mitigation of weight loss, restoration of normal food and fluid intake, and normalization of corticosterone levels. Behavioral analysis showed that treatment with Syn and/or Vlx enhanced depressive-like behaviors and improved spatial learning-memory impairment in stressed rats. Hippocampal dentate gyrus showed stress-induced neuronal cell death, which was attenuated by Syn and/or Vlx treatment. Stress-induced ileum inflammation and increased intestinal permeability were both effectively reduced by the supplementation of Syn. In addition, Syn and Vlx partly contributed to affecting the expression of the glial cell-derived neurotrophic factor in the hippocampus and intestines of stressed rats, suggesting particularly protective effects on both the gut barrier and the brain. This study highlights the intricate interplay between stress physiological responses in the brain and gut. Syn intervention alleviate stress-induced neuronal cell death and modulate depression- and memory impairment-like behaviors, and improve stress-induced gut barrier dysfunction which were similar to those of Vlx. These findings enhance our understanding of stress-related health conditions and suggest the synbiotic intervention may be a promising approach to ameliorate deleterious effects of stress on the gut-brain axis.

SIRT6 modulates paclitaxel and epirubicin resistance and survival in breast cancer.

In this study, we report the identification of a novel role of SIRT6 in both epirubicin and paclitaxel resistance in breast cancer. We found that SIRT6 protein levels are elevated in paclitaxel- and epirubicin-resistant MCF-7 cells compared with the parental sensitive cells. SIRT6 knockout and depletion sensitized cells to both paclitaxel and epirubicin treatment, whereas SIRT6 ectopic overexpression led to increased resistance to paclitaxel and epirubicin. Moreover, our data suggest that SIRT6 could be mediating epirubicin resistance through enhancing the DNA repair response to epirubicin-induced DNA damage. Clonogenic assays also revealed that mouse embryonic fibroblasts (MEFs) lacking SIRT6 have decreased long-term viability in response to epirubicin. The tumour suppressor FOXO3a increases its levels of acetylation in MEFs depleted of SIRT6, whereas its induction by epirubicin is attenuated in breast cancer cells overexpressing SIRT6. Further cell viability studies demonstrate that deletion of FOXO1/3/4 in MEFs can confer sensitivity to both paclitaxel and epirubicin, suggesting that SIRT6 reduces paclitaxel and epirubicin sensitivity, at least in part, through modulating FOXO acetylation and expression. Consistently, immunohistochemical analysis of 118 breast cancer patient samples revealed that high SIRT6 nuclear staining is significantly associated with poorer overall survival (P = 0.018; Kaplan-Meier analysis). Multivariate Cox analysis demonstrated that nuclear SIRT6 staining remained associated with death after correcting for tumour stage and lymph-node involvement (P = 0.033). Collectively, our data suggest that SIRT6 has a role in paclitaxel and epirubicin sensitivity via targeting FOXO proteins and that SIRT6 could be a useful biomarker and therapeutic target for paclitaxel- and epirubicin-resistant cancer.

Purification and Immobilization of Superoxide Dismutase Obtained from Saccharomyces cerevisiae TBRC657 on Bacterial Cellulose and Its Protective Effect against Oxidative Damage in Fibroblasts.

Superoxide dismutase (SOD) is an essential enzyme that eliminates harmful reactive oxygen species (ROS) generating inside living cells. Due to its efficacities, SOD is widely applied in many applications. In this study, the purification of SOD produced from Saccharomyces cerevisiae TBRC657 was conducted to obtain the purified SOD that exhibited specific activity of 513.74 U/mg with a purification factor of 10.36-fold. The inhibitory test revealed that the purified SOD was classified as Mn-SOD with an estimated molecular weight of 25 kDa on SDS-PAGE. After investigating the biochemical characterization, the purified SOD exhibited optimal activity under conditions of pH 7.0 and 35 °C, which are suitable for various applications. The stability test showed that the purified SOD rapidly decreased in activity under high temperatures. To overcome this, SOD was successfully immobilized on bacterial cellulose (BC), resulting in enhanced stability under those conditions. The immobilized SOD was investigated for its ability to eliminate ROS in fibroblasts. The results indicated that the immobilized SOD released and retained its function to regulate the ROS level inside the cells. Thus, the immobilized SOD on BC could be a promising candidate for application in many industries that require antioxidant functionality under operating conditions.

Degradation products of crosslinked silk fibroin scaffolds modulate the immune response but not cell toxicity.

Silk fibroin (SF) scaffolds have widely been used as functional materials for tissue engineering and implantation. For long-term applications, many cross-linking strategies have been developed to enhance the stability and enzymatic degradation of scaffolds. Although the biocompatibility of SF scaffolds has been investigated, less is known about the extent to which the degradation products of these scaffolds affect the host response in the long term after implantation. In this work, we first studied the effect of two different crosslinkers, namely, 1-ethyl-3-(3-dimethylaminopropyl-carbodiimide hydrochloride) (EDC) and glutaraldehyde (GA), on the topology, mechanical stability and enzymatic degradation of SF scaffolds. We found that the SF scaffolds treated with GA (GA-SF) appeared to show an increase in the sheet thickness and a higher elastic modulus when compared to that treated with EDC (EDC-SF) at a similar level of crosslinking degree. The uncrosslinked and both crosslinked SF scaffolds were completely digested by proteinase K but were not susceptible to degradation by collagenase type IV and trypsin. We next investigated the effect of the degradation of SF on the cytotoxicity, genotoxicity, and immunogenicity. The results demonstrated that the degradation products of the uncrosslinked and crosslinked SFs did not trigger cell proliferation, cell death, or genotoxicity in primary human cells, while they appeared to modulate the phenotypes of macrophages. The degradation products of GA-SF promoted pro-inflammatory phenotypes, while those from EDC-SF enhanced polarization towards anti-inflammatory macrophages. Our results demonstrated that the degradation products of SF scaffolds can mediate the immune modulation of macrophages, which can be implemented as a therapeutic strategy to control the long-term immune response during implantation.

The Development of Surface-Modified Liposomes as an Intranasal Delivery System for Group A Streptococcus Vaccines.

Intranasal vaccine administration can overcome the disadvantages of injectable vaccines and present greater efficiency for mass immunization. However, the development of intranasal vaccines is challenged by poor mucosal immunogenicity of antigens and the limited availability of mucosal adjuvants. Here, we examined a number of self-adjuvanting liposomal systems for intranasal delivery of lipopeptide vaccine against group A Streptococcus (GAS). Among them, two liposome formulations bearing lipidated cell-penetrating peptide KALA and a new lipidated chitosan derivative (oleoyl-quaternized chitosan, OTMC) stimulated high systemic antibody titers in outbred mice. The antibodies were fully functional and were able to kill GAS bacteria. Importantly, OTMC was far more effective at stimulating antibody production than the classical immune-stimulating trimethyl chitosan formulation. In a simple physical mixture, OTMC also enhanced the immune responses of the tested vaccine, without the need for a liposome delivery system. The adjuvanting capacity of OTMC was further confirmed by its ability to stimulate cytokine production by dendritic cells. Thus, we discovered a new immune stimulant with promising properties for mucosal vaccine development.

A Shear-Thinning, Self-Healing, Dual-Cross Linked Hydrogel Based on Gelatin/Vanillin/Fe3+ /AGP-AgNPs: Synthesis, Antibacterial, and Wound-Healing Assessment.

A shear-thinning and self-healing hydrogel based on a gelatin biopolymer is synthesized using vanillin and Fe3+ as dual crosslinking agents. Rheological studies indicate the formation of a strong gel found to be injectable and exhibit rapid self-healing (within 10 min). The hydrogels also exhibited a high degree of swelling, suggesting potential as wound dressings since the absorption of large amounts of wound exudate, and optimum moisture levels, lead to accelerated wound healing. Andrographolide, an anti-inflammatory natural product is used to fabricate silver nanoparticles, which are characterized and composited with the fabricated hydrogels to imbue them with anti-microbial activity. The nanoparticle/hydrogel composites exhibit activity against Escherichia coli, Staphylococcus aureus, and Burkholderia pseudomallei, the pathogen that causes melioidosis, a serious but neglected disease affecting southeast Asia and northern Australia. Finally, the nanoparticle/hydrogel composites are shown to enhance wound closure in animal models compared to the hydrogel alone, confirming that these hydrogel composites hold great potential in the biomedical field.

Liposomal Formulations of a Polyleucine-Antigen Conjugate as Therapeutic Vaccines against Cervical Cancer.

Human papilloma virus (HPV) is responsible for all cases of cervical cancer. While prophylactic vaccines are available, the development of peptide-based vaccines as a therapeutic strategy is still under investigation. In comparison with the traditional and currently used treatment strategies of chemotherapy and surgery, vaccination against HPV is a promising therapeutic option with fewer side effects. A peptide derived from the HPV-16 E7 protein, called 8Qm, in combination with adjuvants showed promise as a therapeutic vaccine. Here, the ability of polymerized natural amino acids to act as a self-adjuvating delivery system as a therapeutic vaccine was investigated for the first time. Thus, 8Qm was conjugated to polyleucine by standard solid-phase peptide synthesis and self-assembled into nanoparticles or incorporated in liposomes. The liposome bearing the 8Qm conjugate significantly increased mice survival and decreased tumor growth after a single immunization. Further, these liposomes eradicated seven-day-old well-established tumors in mice. Dendritic cell (DC)-targeting moieties were introduced to further enhance vaccine efficacy, and the newly designed liposomal vaccine was tested in mice bearing 11-day-old tumors. Interestingly, these DCs-targeting moieties did not significantly improve vaccine efficacy, whereas the simple liposomal formulation of 8Qm-polyleucine conjugate was still effective in tumor eradication. In summary, a peptide-based anticancer vaccine was developed that stimulated strong cellular immune responses without the help of a classical adjuvant.