Search Results (11)

Today, most anti-acne treatments employ topical and systemic antibiotics such as erythromycin and clindamycin, which induce cutaneous dysbiosis with adverse side effects to the skin’s normal microbiota, consequently leading to the emergence of antimicrobial resistance. In our quest to discover natural anti-acne bioactives as alternatives, we undertook a research program with the aim to identify a new blend of active ingredients based on the monoterpene phenol moiety. Within this program, we evaluated the in vitro anti-acne efficacy of thymol, Curcuma turmerones and their patented combination “Acnocure” in a cosmetic formulation. The minimum inhibitory concentration (MIC) of Acnocure against C. acnes (ATCC 6919), S. aureus (ATCC 6538), S. epidermidis (ATCC 12228) and C. freneyi (CIP 52.16) was determined to be 0.32, 0.26, 0.47 and 0.11 mg/mL, respectively. In the time-kill curve study against C. acnes, Acnocure, containing thymol 0.25% and 0.1% Curcuma turmerone as well as thymol 0.1% and 0.1% Curcuma turmerone in a cosmetic simplex formulation, demonstrated rapid bactericidal activity with a 4.7 log reduction at pH 5.5, occurring within just two hours of the study and lasting for over 24 h. The killing efficacy was similar to our cosmetic reference benchmark, Effaclar DUO serum, used in the same study. Additionally, thymol, Curcuma turmerones and Acnocure were evaluated in an anti-inflammatory efficacy assay in lipopolysaccharide (LPS)-primed U937 macrophages model and demonstrated moderate inhibition of interleukin-1β (IL-1β) at 100 µg/mL and significant inhibition of prostaglandin E-2 (PGE-2) at 1 µg/mL, respectively. Further evidence gathered on thymol and Curcuma turmerones in an IL-1α-stimulated dermal fibroblast model showed >90% inhibition of PGE-2 release between 2 µg/mL and 30 µg/mL concentrations. These promising results position Acnocure as a natural alternative for the replacement of synthetic corticosteroids and antibiotics with potent anti-acne skincare properties. Full article

Mycoplasma gallisepticum (MG) is recognized as a principal causative agent of avian chronic respiratory disease, inflicting substantial economic losses upon the poultry industry. However, the extensive use of conventional antibiotics has resulted in the emergence of drug resistance and various challenges in their clinical application. Consequently, there is an urgent need to identify effective therapeutic agents for the prevention and treatment of mycoplasma-induced respiratory disease in avian species. AMP-activated protein kinase (AMPK) holds significant importance as a regulator of cellular energy metabolism and possesses the capacity to exert an anti-inflammatory effect by virtue of its downstream protein, SIRT1. This pathway has shown promise in counteracting the inflammatory responses triggered by pathogenic infections, thus providing a novel target for studying infectious inflammation. Quercetin possesses anti-inflammatory activity and has garnered attention as a potential alternative to antibiotics. However, there exists a gap in knowledge concerning the impact of this activation on MG-induced inflammatory damage. To address this knowledge gap, we employed AlphaFold2 prediction, molecular docking, and kinetic simulation methods to perform a systematic analysis. As expected, we found that both quercetin and the AMPK activator AICAR activate the chicken AMPKγ1 subunit in a similar manner, which was further validated at the cellular level. Our project aims to unravel the underlying mechanisms of quercetin’s action as an agonist of AMPK against the inflammatory damage induced by MG infection. Accordingly, we evaluated the effects of quercetin on the prevention and treatment of air sac injury, lung morphology, immunohistochemistry, AMPK/SIRT1/NF-κB pathway activity, and inflammatory factors in MG-infected chickens. The results confirmed that quercetin effectively inhibits the secretion of pro-inflammatory cytokines such as IL-1β, TNF-α, and IL-6, leading to improved respiratory inflammation injury. Furthermore, quercetin was shown to enhance the levels of phosphorylated AMPK and SIRT1 while reducing the levels of phosphorylated P65 and pro-inflammatory factors. In conclusion, our study identifies the AMPK cascade signaling pathway as a novel cellular mediator responsible for quercetin’s ability to counter MG-induced inflammatory damage. This finding highlights the potential significance of this pathway as an important target for anti-inflammatory drug research in the context of avian respiratory diseases. Full article

Diarrhea has been a global health problem for centuries, and the treatment has become increasingly difficult duo to the antibiotics overuse and resistance. Quercetin is a common flavonoid of extracts of vegetables, fruits, and traditional Chinese herbs, however, the mechanism of quercetin alleviating LPS-induced duodenal inflammation remains elusive. Specific pathogen-free chicken embryos (n = 120) were allocated to groups including control, PBS with or without alcohol, LPS (125 ng/egg) with or without quercetin (10, 20, or 40 nmol/egg, respectively), and quercetin groups (10, 20, or 40 nmol/egg). Fifteen day-old embryonated eggs were inoculated with abovementioned solutions via the allantoic cavity. At embryonic day 19, the duodena of the embryos were collected for histopathological examination, RNA extraction and real-time polymerase chain reaction, immunohistochemical investigations, and Western blotting. The results demonstrated quercetin enhanced the inflammatory cell infiltration in the Peyer’s patch of the intestinal mucosa after LPS induction. The LPS-induced expressions of these inflammation-related factors (TLR4, IL-1β, MMP3, MMP9, NFKB1, IFNγ, IL-8, IL-6) were completely blocked by quercetin. Quercetin also decreased the protein expression of TLR4, IL-1β, MMP3, and MMP9 after LPS induction. Quercetin could down-regulate autophagy gene expression (ATG5, LC3-1, LC3-2, and LKB1), and decreased the protein expression of ATG5, and LC3-1/LC3-2 after LPS induction. Quercetin treatment prevented LPS-induced increases of the gene expressions of programmed cell death factors (TNFα, Fas, CASP1, CASP3, CASP12, Drp1, and RIPK1); meanwhile, quercetin decreased the protein expression of CASP1 and CASP3 after LPS challenge. LPS reduced the gene expression of mucin 2, but upregulated the mRNA and protein expression of claudin 1, occludin, and ZO-1, and this was balanced by quercetin. This evidence suggests that quercetin can alleviate duodenal inflammation induced by LPS through modulating autophagy, programmed cell death, intestinal barrier function. Full article

Emulsion gel, a novel oral delivery carrier, provides the possibility to co-load hydrophilic and lipophilic nutrients simultaneously. In this study, duo-induction methods of laccase and glucono-δ-lactone (L&GDL) or laccase and transglutaminase (L&MTG) were used to prepare the soy protein isolate-sugar beet pectin (SPI-SBP) emulsion gel. The textural data of the emulsion gel was normalized to analyze the effect of different induction methods on the gel property of the SPI-SBP emulsion gels. The characterization studies showed the structure of L&MTG emulsion gel was denser with a lower swelling ratio and reduced degree of digestion, compared with L&GDL emulsion gel. Moreover, the release profiles of both β-carotene and riboflavin co-loaded in the SPI-SBP emulsion gels were correlated to the digestion patterns of the gel matrix; the controlled-release of encapsulated functional factors was regulated by a gel network induced by different induction methods, mainly due to the resulting porosity of the structure and swelling ratio during digestion. In conclusion, SPI-SBP emulsion gels have the capability of encapsulating multiple functional factors with different physicochemical properties. Full article

This study aimed to conduct a comparative study on the microstructure and mechanical performance of 5083, 6005A and 7N01 Al joints used in China Railway High-speed (CRH) trains. We connected 10 mm-thick plates by three-layer and three-pass gas metal arc welding (GMAW). The results indicated that 6005A and 7N01 Al joints were more sensitive to grain boundary liquation in the partially melted zone (PMZ) than 5083 Al joins. Besides, recrystallization was obtained in heat-affected zones (HAZ). The 5083 Al joints experienced the most severe recrystallization and the grain size changed from 6.32 (BM) to 32.44 (HAZ) μm duo to intracrystalline strain induced by cold-rolled processes. The 7N01 Al alloys experienced the lowest extent of recrystallization and the grain size increased from 5.32 (BM) to 22.31 (HAZ) μm. Furthermore, significant precipitate evolution in the HAZ was observed. Original thin β” precipitates dissolved in HAZ of 6005A Al joints and transformed to the softer β phase. However, less precipitation transition was examined in 5083 and 7N01 Al joints. The precipitates’ evolution produced a softening region in HAZ of 6005A joints where the hardness was only 55 HV. The microhardness profile of the other two Al joints was less affected. The tensile strength of 5083, 6005A, and 7N01 Al alloy joints reached 323, 206 and 361 MPa, respectively. The 5083 Al and 6005A Al joints failed at HAZ near the fusion line while 7N01 Al joints failed at the fusion zone owing to the high strength of the base metal. The liquation, coarse grains by recrystallization, and precipitate evolution all decreased local strength, resulting in the fracture at HAZ. Full article

Epilepsy is a chronic neurodegenerative disease characterized by multiple seizures, hereto 35% of patients remain poor responders. Phenytoin (PHT; 20 and 40 mg/kg) and thymoquinone (THQ; 40 and 80 mg/kg) were given alone and as a low dose combination for 14 days (p.o), prior to challenge with maximal electroshock (MES; 180 mA, 220 V, 0.2 s). Apart from observing convulsions, hippocampal mTOR, IL-1β, IL-6 and TNF-α levels were measured. Hippocampal histomorphological analysis was also conducted. In vitro cell line studies and molecular docking studies were run in parallel. The results revealed the synergistic potential of the novel duo-drug combination regimen: PHT (20 mg/kg) and THQ (40 mg/kg) against MES-induced convulsions. MES amplified signaling through mTOR, and inflated the levels of proinflammatory markers (IL-1β, IL-6 and TNF-α), which was significantly averted (p < 0.001) with the said drug combination. The computational studies revealed that PHT and THQ cooperatively bind the active site on Akt (upstream target of m-TOR) and establish a good network of intermolecular interactions, which indicates the sequential inhibition of PI3K/Akt/m-TOR signaling with the combination. The combination also increased cell viability by 242.81% compared to 85.66% viability from the the toxic control. The results suggest that the PHT and THQ in combination possesses excellent anticonvulsant and neuroprotective effects. Full article

The emergence and spread of insecticide resistance among the main malaria vectors is threatening the effectiveness of vector control interventions in Senegal. The main drivers of this resistance in the Anopheles gambiae complex (e.g., An. gambiae and Anopheles coluzzii) remains poorly characterized in Senegal. Here we characterized the main target site and metabolic resistances mechanisms among the An. gambiae and An. coluzzii populations from their sympatric and allopatric or predominance area in Senegal. Larvae and pupae of An. gambiae s.l. were collected, reared to adulthood, and then used for insecticides susceptibility and synergist assays using the WHO (World Health Organisation) test kits for adult mosquitoes. The TaqMan method was used for the molecular characterization of the main target site insecticide resistance mechanisms (Vgsc-1014F, Vgsc-1014S, N1575Y and G119S). A RT-qPCR (Reverse Transcriptase-quantitative Polymerase Chaine Reaction) was performed to estimate the level of genes expression belonging to the CYP450 (Cytochrome P450) family. Plasmodium infection rate was investigated using TaqMan method. High levels of resistance to pyrethroids and DDT and full susceptibility to organophosphates and carbamates where observed in all three sites, excepted a probable resistance to bendiocarb in Kedougou. The L1014F, L1014S, and N1575Y mutations were found in both species. Pre-exposure to the PBO (Piperonyl butoxide) synergist induced a partial recovery of susceptibility to permethrin and full recovery to deltamethrin. Subsequent analysis of the level of genes expression, revealed that the CYP6Z1 and CYP6Z2 genes were over-expressed in wild-resistant mosquitoes compared to the reference susceptible strain (Kisumu), suggesting that both the metabolic resistance and target site mutation involving kdr mutations are likely implicated in this pyrethroid resistance. The presence of both target-site and metabolic resistance mechanisms in highly pyrethroid-resistant populations of An. gambiae s.l. from Senegal threatens the effectiveness and the sustainability of the pyrethroid-based tools and interventions currently deployed in the country. The Kdr-west mutation is widely widespread in An. coluzzii sympatric population. PBO or Duo nets and IRS (Indoor Residual Spraying) with organophosphates could be used as an alternative measure to sustain malaria control in the study area. Full article

Sediment resuspension induces endogenous nutrient release in shallow lakes, which has been demonstrated to be associated with eutrophication. In addition to natural wind-driven resuspension, navigable shallow lakes (such as Lake Taihu, China) also experience resuspension from human activities, such as ship waves. Both processes determine the intensity, frequency, and duration of sediment resuspension, and may consequently affect the pattern of cyanobacteria blooms in the lake. In this study, acoustic Doppler Velocimeter (ADV), Optical Backscatter Sensor (OBS), and temperature wave tide gauge (instrument model :RBR duo TD|wave) were placed in an observation platform in the lake to obtain high-frequency flow velocities, suspended sediment concentration (SSC), and wave parameters before, during, and after a cargo ship passed by. We found that the ship wave disturbance intensity is greatly influenced by the draft depth. The movement generated by ship disturbance is primarily horizontal rather than vertical. Compared with the wind-induced wave, the disturbance caused by the ship waves has a high intensity, short duration, and narrow range of influence. The maximum total shear stress under ship disturbance can reach 9~90 times the critical shear stress under a natural state. Therefore, the effect of ship waves on sediment resuspension near the channel of Lake Taihu is much greater than that of wind-induced waves. These findings represent an important step towards understanding the quantitative relationship between ship wave disturbance and sediment resuspension, and lay the foundation for future research in order to understand and control the eutrophication of shallow lakes. Full article

Benefits associated with probiotic use have been reported; however, the mechanisms behind these benefits are poorly understood. The effects of a probiotic formulation (MegaDuo™) containing Bacillus coagulans SC208 and Bacillus subtilis HU58 on intestinal permeability and immune markers was assessed using a combination of the in vitro gut model, the mucosal simulator of the human intestinal microbial ecosystem (M-SHIME^®), and an in vitro inflammatory bowel disease-like Caco-2/THP1 co-culture model in both healthy and antibiotic-induced dysbiosis conditions. Established M-SHIME^® proximal colon vessels were treated with/without clindamycin (1 week) and then with/without daily MegaDuo™ treatment (2 weeks). The mucosal and luminal microbial communities were sampled weekly. Suspensions were removed from the proximal colon vessels after 1 and 2 weeks of MegaDuo™ treatment and added to the co-culture system. Transepithelial resistance (membrane barrier function), cytokine/chemokine release, and NFκB activity were then measured. Under conditions of antibiotic-induced dysbiosis, suspensions from MegaDuo™ treated vessels showed reduced gut membrane barrier damage and decreased levels of TNFα and IL-6 compared with suspensions from untreated vessels; no appreciable differences were observed under healthy conditions. MegaDuo™ treatment had no effect on NFκB activity of THP1-Blue™ cells. The potential benefits of MegaDuo™ treatment appeared most evident after 2 weeks of treatment. Full article

An increasing number of investigations have been performed on the phytotoxicity of carbon-based nanomaterials duo to their extensive use in various fields. In the present study, we investigated the phytotoxicity of unfunctionalized graphene oxide (GO) and amine-functionalized graphene oxide (G-NH₂) on wheat (Triticum aestivum) in the concentration range from 125 to 2000 μg/mL after 9 days of hydroponic culture. Our results found that the incubation with both nanomaterials did not affect the final seed germination rate, despite some influence in the initial stage. Transmission electron microscopy (TEM) observations indicated that exposure to GO at a high concentration (above 1000 μg/mL) resulted in a severe loss of morphology of seedlings, and a decrease in root length, shoot length and relative biomass, along with obvious damage to plant tissue structures (root, stem and leaf) when compared with the control. GO induced increased damage to root cells, which were determined by electrolyte leakage. Conversely, the plant growth was enhanced under G-NH₂ exposure, and the root and stem lengths were increased by 19.27% and 19.61% at 2000 μg/mL, respectively. The plant tissue structures were not affected, and neither GO nor G-NH₂ were observed to accumulate in the wheat plant root cells. The present investigations provide important information for evaluation of the environmental safety of GO and better understanding plant-nanoparticle interactions. Full article

The present study shows a new connection of protein tyrosine phosphatase interacting protein 51 (PTPIP51) to the nuclear factor κB (NFκB) signalling pathway. PTPIP51 mRNA and protein expression is regulated by RelA. If bound to the PTPIP51 promoter, RelA repress the mRNA and protein expression of PTPIP51. The parallel treatment with pyrrolidine dithiocarbamate (PDTC) reversed the suppression of PTPIP51 protein expression induced by TNFα. Using the intensity correlation analysis PTPIP51 verified a co-localization with RelA, which is also regulated by TNFα administration. Moreover, the direct interaction of PTPIP51 and RelA was established using the DuoLink proximity ligation assay. IκBα, the known inhibitor of RelA, also interacted with PTPIP51. This hints to the fact that in un-stimulated conditions PTPIP51 forms a complex with RelA and IκBα. The PTPIP51/RelA/IκBα complex is modulated by TNFα. Interestingly, the impact on the mitogen activated protein kinase pathway was negligible except in highest TNFα concentration. Here, PTPIP51 and Raf-1 interactions were slightly repressed. The newly established relationship of PTPIP51 and the NFκB signaling pathway provides the basis for a possible therapeutic impact. Full article