Propellant Free Pressurized Spray System of Etodolac to Manage Acute Pain Conditions: In Vitro and In Vivo Evaluation.

This study aimed to develop a propellant-free topical spray formulation of Etodolac (BCS-II), a potent NSAID, which could be beneficial in the medical field for the effective treatment of pain and inflammation conditions. The developed novel propellant-free spray formulation is user-friendly, cost-effective, propellant-free, eco-friendly, enhances the penetration of Etodolac through the skin, and has a quick onset of action. Various formulations were developed by adjusting the concentrations of different components, including lecithin, buffering agents, film-forming agents, plasticizers, and permeation enhancers. The prepared propellant-free spray formulations were then extensively characterized and evaluated through various in vitro, ex vivo, and in vivo parameters. The optimized formulation exhibits an average shot weight of 0.24 ± 0.30 ml and an average drug content or content uniformity of 87.3 ± 1.01% per spray. Additionally, the optimized formulation exhibits an evaporation time of 3 ± 0.24 min. The skin permeation study demonstrated that the permeability coefficients of the optimized spray formulation were 21.42 cm/h for rat skin, 13.64 cm/h for mice skin, and 18.97 cm/h for the Strat-M membrane. When assessing its potential for drug deposition using rat skin, mice skin, and the Strat-M membrane, the enhancement ratios for the optimized formulation were 1.88, 2.46, and 1.92, respectively against pure drug solution. The findings from our study suggest that the propellant-free Etodolac spray is a reliable and safe topical formulation. It demonstrates enhanced skin deposition, and improved effectiveness, and is free from any skin irritation concerns.

Obesity and polycystic ovary syndrome influence on intestinal permeability at fasting, and modify the effect of diverse macronutrients on the gut barrier.

Women with the extremely prevalent polycystic ovary syndromegather multiple cardiovascular risk factors and chronic subclinical inflammation. Interactions between diet, adiposity, and gut microbiota modulate intestinal permeabilityand bacterial product translocation, and may contribute to the chronic inflammation process associated with the polycystic ovary syndrome. In the present study, we aimed to address the effects of obesity, functional hyperandrogenism, and diverse oral macronutrients on intestinal permeabilityby measuring circulating markers of gut barrier dysfunction and endotoxemia. Participants included 17 non-hyperandrogenic control women, 17 women with polycystic ovary syndrome, and 19 men that were submitted to glucose, lipid, and protein oral loads. Lipopolysaccharide-binding protein, plasma soluble CD14, succinate, zonulin family peptide, and glucagon-like peptide-2 were determined at fasting and after oral challenges. Macronutrient challenges induced diverse changes on circulating intestinal permeabilitybiomarkers in the acute postprancial period, with lipids and proteins showing the most unfavorable and favorable effects, respectively. Particularly, lipopolysaccharide-binding protein, zonulin family peptide, and glucagon-like peptide-2 responses were deregulated by the presence of obesity after glucose and lipid challenges. Obese subjects showed higher fasting intestinal permeabilitybiomarkers levels than non-obese individuals, except for plasma soluble CD14. The polycystic ovary syndromeexacerbated the effect of obesity further increasing fasting glucagon-like peptide-2, lipopolysaccharide-binding protein, and succinate concentrations. We observed specific interactions of the polycystic ovary syndromewith obesity in the postprandial response of succinate, zonulin family peptide, and glucagon-like peptide-2. In summary, obesity and polycystic ovary syndromemodify the effect of diverse macronutrients on the gut barrier, and alsoinfluence intestinal permeabilityat fasting,contributing to the morbidity of functional hyperandrogenism by inducing endotoxemia and subclinical chronic inflammation.

Efficacy of Laurus nobilis L. for Tight Junction Protein Imbalance in Leaky Gut Syndrome.

Laurus nobilis L. (LNL) belongs to the evergreen Lauraceae family. It is native to the Mediterranean and widely distributed in the southern United States, Europe, and the Middle East. LNL is rich in active ingredients of the sesquiterpene lactone series and has been reported to have antioxidant, anti-inflammatory, and anticancer effects. And parthenolide, known as a sesquiterpene lactone-based compound, inhibits the activation of lipopolysaccharide-binding protein (LBP), which is a major trigger for leaky gut syndrome. However, the effectiveness of LNL in improving the state of increased intestinal permeability has not yet been reported. Therefore, we demonstrated the efficacy of LNL, which is known to be rich in parthenolide, in improving intestinal permeability induced by IL-13. We investigated the improvement in permeability and analyzed major tight junction proteins (TJs), permeability-related mechanisms, weight and disease activity indices, and corresponding cytokine mechanisms. LNL maintained TJs homeostasis and clinical improvement by reducing increased claudin-2 through the inhibition of IL-13/STAT6 activation in TJ-damaged conditions. These results are expected to be effective in preventing leaky gut syndrome through the TJ balance and to further improve intestinal-related diseases, such as inflammatory bowel disease.

Ketogenic Diet Protects from Experimental Colitis in a Mouse Model Regardless of Dietary Fat Source.

While ketogenic diets (KDs) may have potential as adjunct treatments for gastrointestinal diseases, there is little knowledge on how the fat source of these diets impacts intestinal health. The objective of this study was to investigate how the source of dietary fat of KD influences experimental colitis. We fed nine-week-old male C57BL/6J mice (n = 36) with a low-fat control diet or KD high either in saturated fatty acids (SFA-KD) or polyunsaturated linoleic acid (LA-KD) for four weeks and then induced colitis with dextran sodium sulfate (DSS). To compare the diets, we analyzed macroscopic and histological changes in the colon, intestinal permeability to fluorescein isothiocyanate-dextran (FITC-dextran), and the colonic expression of tight junction proteins and inflammatory markers. While the effects were more pronounced with LA-KD, both KDs markedly alleviated DSS-induced histological lesions. LA-KD prevented inflammation-related weight loss and the shortening of the colon, as well as preserved Il1b and Tnf expression at a healthy level. Despite no significant between-group differences in permeability to FITC-dextran, LA-KD mitigated changes in tight junction protein expression. Thus, KDs may have preventive potential against intestinal inflammation, with the level of the effect being dependent on the dietary fat source.

A Patented Dietary Supplement (Hydroxy-Methyl-Butyrate, Carnosine, Magnesium, Butyrate, Lactoferrin) Is a Promising Therapeutic Target for Age-Related Sarcopenia through the Regulation of Gut Permeability: A Randomized Controlled Trial.

Adequate diet, physical activity, and dietary supplementation with muscle-targeted food for special medical purposes (FSMP) or dietary supplement (DS) are currently considered fundamental pillars in sarcopenia treatment. The aim of this study is to evaluate the effectiveness of a DS (containing hydroxy-methyl-butyrate, carnosine, and magnesium, for its action on muscle function and protein synthesis and butyrate and lactoferrin for their contribution to the regulation of gut permeability and antioxidant/anti-inflammation activity) on muscle mass (assessed by dual X-ray absorptiometry (DXA)), muscle function (by handgrip test, chair test, short physical performance battery (SPPB) test, and walking speed test), inflammation (tumor necrosis factor-alpha (TNF-a), C-reactive protein (CRP), and visceral adipose tissue (VAT)) and gut axis (by zonulin). A total of 59 participants (age 79.7 ± 4.8 years, body mass index 20.99 ± 2.12 kg/m2) were enrolled and randomly assigned to intervention (n = 30) or placebo (n = 28). The skeletal muscle index (SMI) significantly improved in the supplemented group compared to the placebo one, +1.02 (CI 95%: -0.77; 1.26), p = 0.001; a significant reduction in VAT was observed in the intervention group, -70.91 g (-13.13; -4.70), p = 0.036. Regarding muscle function, all the tests significantly improved (p = 0.001) in the supplemented group compared to the placebo one. CRP, zonulin, and TNF-alpha significantly decreased (p = 0.001) in intervention, compared to placebo, -0.74 mg/dL (CI 95%: -1.30; -0.18), -0.30 ng/mL (CI 95%: -0.37; -0.23), -6.45 pg/mL (CI 95%: -8.71; -4.18), respectively. This DS improves muscle mass and function, and the gut muscle has emerged as a new intervention target for sarcopenia.

Differential Bioactivation Profiles of Different GS-441524 Prodrugs in Cell and Mouse Models: ProTide Prodrugs with High Cell Permeability and Susceptibility to Cathepsin A Are More Efficient in Delivering Antiviral Active Metabolites to the Lung.

We assessed factors that determine the tissue-specific bioactivation of ProTide prodrugs by comparing the disposition and activation of remdesivir (RDV), its methylpropyl and isopropyl ester analogues (MeRDV and IsoRDV, respectively), the oral prodrug GS-621763, and the parent nucleotide GS-441524 (Nuc). RDV and MeRDV yielded more active metabolite remdesivir-triphosphate (RDV-TP) than IsoRDV, GS-621763, and Nuc in human lung cell models due to superior cell permeability and higher susceptivity to cathepsin A. Intravenous administration to mice showed that RDV and MeRDV delivered significantly more RDV-TP to the lung than other compounds. Nevertheless, all four ester prodrugs exhibited very low oral bioavailability (<2%), with Nuc being the predominant metabolite in blood. In conclusion, ProTides prodrugs, such as RDV and MeRDV, are more efficient in delivering active metabolites to the lung than Nuc, driven by high cell permeability and susceptivity to cathepsin A. Optimizing ProTides' ester structures is an effective strategy for enhancing prodrug activation in the lung.

The water extracts from the oil cakes of Prinsepia utilis repair the epidermal barrier via up-regulating Corneocyte Envelope-proteins, lipid synthases, and tight junction proteins.

ETHNOPHARMACOLOGICAL RELEVANCE: Prinsepia utilis Royle, native to the Himalayan region, has a long history of use in traditional medicine for its heat-clearing, detoxification, anti-inflammatory, and analgesic properties. Oils extracted from P. utilis seeds are also used in cooking and cosmetics. With the increasing market demand, this extraction process generates substantial industrial biowastes. Recent studies have found many health benefits with using aqueous extracts of these biowastes, which are also rich in polysaccharides. However, there is limited research related to the reparative effects of the water extracts of P. utilis oil cakes (WEPUOC) on disruptions of the skin barrier function. AIM OF THE STUDY: This study aimed to evaluate the reparative efficacy of WEPUOC in both acute and chronic epidermal permeability barrier disruptions. Furthermore, the study sought to explore the underlying mechanisms involved in repairing the epidermal permeability barrier. MATERIALS AND METHODS: Mouse models with induced epidermal disruptions, employing tape-stripping (TS) and acetone wiping (AC) methods, were used. The subsequent application of WEPUOC (100 mg/mL) was evaluated through various assessments, with a focus on the upregulation of mRNA and protein expression of Corneocyte Envelope (CE) related proteins, lipid synthase-associated proteins, and tight junction proteins. RESULTS: The polysaccharide was the major phytochemicals of WEPUOC and its content was determined as 32.2% by the anthranone-sulfuric acid colorimetric method. WEPUOC significantly reduced transepidermal water loss (TEWL) and improved the damaged epidermal barrier in the model group. Mechanistically, these effects were associated with heightened expression levels of key proteins such as FLG (filaggrin), INV (involucrin), LOR (loricrin), SPT, FASN, HMGCR, Claudins-1, Claudins-5, and ZO-1. CONCLUSIONS: WEPUOC, obtained from the oil cakes of P. utilis, is rich in polysaccharides and exhibits pronounced efficacy in repairing disrupted epidermal barriers through increased expression of critical proteins involved in barrier integrity. Our findings underscore the potential of P. utilis wastes in developing natural cosmetic prototypes for the treatment of diseases characterized by damaged skin barriers, including atopic dermatitis and psoriasis.

Enhanced gas separation performance for H2 purification using MIL-68(ln)-nh2/PES mixed-matrix membranes.

The growing demand for sustainable and efficient gas separation technologies has prompted the exploration of advanced materials to enhance the gas permeability and selectivity. Polyethersulfone (PES) membranes are widely used in gas separation, gas upgrading, and clean energy production owing to their environmental friendliness and low cost. However, their gas permeability and selectivity can be further improved for commercial application. This study explored the incorporation of 10 wt % of MIL-68(ln)-NH2 into PES membranes using a phase-inversion approach to enhance gas permeability and selectivity. The morphological, structural, and thermal properties of the resulting MOF/PES membrane were characterized using SEM, AFM, BET, XRD, FTIR, and TGA-DTG. Gas permeation experiments were conducted using different gases (CO2, N2, CH4, and H2) under different heating conditions (20-60 °C) to evaluate the gas permeability and selectivity of the MOF/PES membrane. The results showed that the incorporation of MOF into the mixed matrix membrane (MMMs) led to a 9% increase in porosity, 87% reduction in roughness, and 32% decrease in pore size compared to neat PES membranes. Significant changes in the morphology, crystallinity, and thermal stability were observed, with notable improvements of up to 22%. Moreover, the MOF/PES membrane exhibited high gas permeability (CO2 = 124656, N2 = 83650, CH4 = 159298, and H2 = 427075 Barrer) and selectivity (H2/N2 = 5.7, H2/CO2 = 4, CH4/N2 = 2, and CH4/CO2 = 1.7) for flammable gases. The optimal gas separation performance was observed at 20 °C and 60 °C for H2/N2 and H2/CO2 separation, respectively. These findings demonstrate the potential of MOF-based PES membranes for gas separation applications, particularly in H2 purification.

Brain histamine improves colonic hyperpermeability through the basal forebrain cholinergic neurons, adenosine A2B receptors and vagus nerve in rats.

Intestinal barrier dysfunction, leaky gut, is implicated in various diseases, including irritable bowel syndrome (IBS) and neurodegenerative conditions like Alzheimer's disease. Our recent investigation revealed that basal forebrain cholinergic neurons (BFCNs), critical for cognitive function, receive signals from butyrate and orexin, playing a role in regulating intestinal barrier function through adenosine A2B signaling and the vagus. This study explores the involvement and function of brain histamine, linked to BFCNs, in the regulation of intestinal barrier function. Colonic permeability, assessed by quantifying absorbed Evans blue in rat colonic tissue, showed that histamine did not affect increased colonic permeability induced by LPS when administered subcutaneously. However, intracisternal histamine administration improved colonic hyperpermeability. Elevating endogenous histamine levels in the brain with SKF91488, a histamine N-methyltransferase inhibitor, also improved colonic hyperpermeability. This effect was abolished by intracisternal chlorpheniramine, an histamine H1 receptor antagonist, not ranitidine, an H2 receptor antagonist. The SKF91488-induced improvement in colonic hyperpermeability was blocked by vagotomy, intracisternal pirenzepine (suppressing BFCNs activity), or alloxazine (an adenosine A2B receptor antagonist). Additionally, intracisternal chlorpheniramine injection eliminated butyrate-induced improvement in colonic hyperpermeability. These findings suggest that brain histamine, acting via the histamine H1 receptor, regulates intestinal barrier function involving BFCNs, adenosine A2B signaling, and the vagus. Brain histamine appears to centrally regulate intestinal barrier function influenced by butyrate, differentiating its actions from peripheral histamine in conditions like IBS, where mast cell-derived histamine induces leaky gut. Brain histamine emerges as a potential pharmacological target for diseases associated with leaky gut, such as dementia and IBS.

Remediation of oily-produced water from high-salinity oilfield using a low-cost, high-alumina calcium bentonite hollow fiber membrane.

Discharging improperly treated oily-produced water (OPW) into the environment can have significant negative impacts on environmental sustainability. It can lead to pollution of water sources, damage to aquatic ecosystems and potential health hazards for individuals living in the affected areas. Ceramic hollow fiber membrane (CHFM) technology is one of the most effective OPW treatment methods for achieving high oil removal efficiency while maintaining membrane water permeability. In this study, low-cost calcium bentonite hollow fiber membranes (CaB-HFMs) were prepared from high-alumina calcium bentonite clay with various preparation parameters, including calcium bentonite content, sintering temperature, air gap distance and bore fluid rate. The prepared CaB-HFMs were then subjected to characterization using scanning electron microscopy (SEM), a three-point bending test, porosity, average pore size, hydraulic resistance and flux recovery ratio (FRR) analysis. Statistical analysis employing central composite design (CCD) assessed the interaction between the parameters and their effect on CaB-HFM water permeability and oil removal efficiency. Higher ceramic content and sintering temperature led to reduced porosity, smaller pore size and higher mechanical strength. In contrast, increasing the air gap distance and bore fluid rate exhibit different trends, resulting in higher porosity and pore size, along with weaker mechanical strength. Other than that, all of the CaB-HFMs displayed low hydraulic resistance (<0.01 m2 h.bar/L) and high FRR value (up to 95.2%). Based on CCD, optimal conditions for CaB-HFM were determined as follows: a calcium bentonite content of 50 wt.%, a sintering temperature of 1096 °C, an air gap distance of 5 cm and a bore fluid rate of 10 mL/min, with the desirability value of 0.937. Notably, the optimized CaB-HFMs demonstrated high oil removal efficiency of up to 99.7% with exceptional water permeability up to 535.2 L/m2.h.bar. The long-term permeation study also revealed it was capable of achieving a high average water permeation and a stable oil rejection performance of 522.15 L/m2.h.bar and 99.8%, respectively, due to their inherent hydrophilic and antifouling characteristics, making it practical for OPW treatment application.

Pore structure characterization and its influence on aqueous phase trapping damage in tight gas sandstone reservoirs.

Aqueous phase trapping (APT), which is one of the most prominent damages, seriously restricts the natural gas production in tight gas sandstone with low permeability. Pore size and microscopic pore structures are the most important factors to determine the water blocking damage. In this paper, 9 core samples from tight gas sandstone with various physical properties were employed, and the pore size distribution (PSD) of the core samples were investigated by high pressure mercury intrusion tests (HPMI). Results showed that the porosity of core samples ranges from 5.68% to 13.7%, and the permeability ranges from 0.00456 to 7.86 mD, which is a typical tight reservoir with strong heterogeneity. According to the HPMI capillary curve, the cores can be divided into two types: Type I and Type II, and the pore sizes of type I are larger than that of type II. Fractal distributions were obtained using HPMI data to further determine the pore structure characteristics of tight reservoirs. The pore structures of tight sandstones display the multifractal fractal feature: D1 corresponding to macro-pores, and D2 corresponding to fractal dimension of micro-pores. Furthermore, APT damage was determined by the permeability recovery ratios (Kr) after gas flooding tests. The correlation of Kr and PSD and fractal dimensions were jointly analyzed in tight gas sandstone. Although positive correlations between pore size parameters and the permeability recovery ratios were observed with relatively weak correlations, for those core samples with very close permeability, pore size parameters (both permeability and PSD) is inadequate in clarifying this damage. The fractal dimension can well describe the complexity and heterogeneity of flow channels in pores, which can become the determining factor to distinguish the flow capacity of tight sandstone. The D2 for samples of type I and type II exhibited a good negative relation with Kr with a correlation coefficient of 0.9878 and 0.7723, respectively. The significance of this finding is that for tight gas sandstone, fractal dimensions, especially the small pore fractal dimension (D2), can be used to predict the possible APT damage very well.

A Novel Cocrystal of Daidzein with Piperazine to Optimize the Solubility, Permeability and Bioavailability of Daidzein.

It is well known that daidzein has various significant medicinal values and health benefits, such as anti-oxidant, anti-inflammatory, anti-cancer, anti-diabetic, cholesterol lowering, neuroprotective, cardioprotective and so on. To our disappointment, poor solubility, low permeability and inferior bioavailability seriously limit its clinical application and market development. To optimize the solubility, permeability and bioavailability of daidzein, the cocrystal of daidzein and piperazine was prepared through a scientific and reasonable design, which was thoroughly characterized by single-crystal X-ray diffraction, powder X-ray diffraction, Fourier transform infrared spectroscopy, differential scanning calorimetry and thermogravimetric analysis. Combining single-crystal X-ray diffraction analysis with theoretical calculation, detailed structural information on the cocrystal was clarified and validated. In addition, a series of evaluations on the pharmacogenetic properties of the cocrystal were investigated. The results indicated that the cocrystal of daidzein and piperazine possessed the favorable stability, increased solubility, improved permeability and optimized bioavailability of daidzein. Compared with the parent drug, the formation of cocrystal, respectively, resulted in 3.9-, 3.1-, 4.9- and 60.8-fold enhancement in the solubility in four different media, 4.8-fold elevation in the permeability and 3.2-fold in the bioavailability of daidzein. Targeting the pharmaceutical defects of daidzein, the surprising elevation in the solubility, permeability and bioavailability of daidzein was realized by a clever cocrystal strategy, which not only devoted assistance to the market development and clinical application of daidzein but also paved a new path to address the drug-forming defects of insoluble drugs.

Enhancing the bioavailability and antioxidant activity of natamycin E235-ferulic acid loaded polyethylene glycol/carboxy methyl cellulose films as anti-microbial packaging for food application.

This study investigated the development of biodegradable films made from a combination of polyethylene glycol (PEG), carboxymethyl cellulose (CMC) and mixtures from natamycin and ferulic acid. The films were characterized for their surface microstructure, antioxidant activity, thermal stability, mechanical properties, permeability and antifungal/bacterial activity. The addition of natamycin and ferulic acid to the film matrix enhanced antioxidant activity, thermal stability, antimicrobial activity, reduced the water vapor permeability (WVP) to 1.083 × 10-10 g × m-1s-1Pa-1, imparted opaque color and increased opacity up to 3.131 A mm-1. The attendance of natamycin and ferulic acid inside films created a clear roughness shape with agglomerates on the surface of films and caused a clear inhibition zone for Aspergillus niger, E. coli and C. botulinum. The utilization of PG/CMC/N-F packaging material on Ras cheese had a noticeable effect, resulting in a slight decrease in moisture content from 34.23 to 29.17 %. Additionally, it helped maintain the titrable acidity within the range of 0.99 % to 1.11 % and the force required for puncture from 0.035 to 0.052 N with non-significant differences. Importantly, these changes did not significantly affect the sensory qualities of Ras cheese during the storage period.

Development of ultra-thin poly(L-lactic acid)-based films integrating toughness, barrier properties, and gas selectivity: Towards gas-permeation controllable green food packaging.

High costs and low performance have constrained the application of bio-based materials in food packaging. Herein, a series of ultra-thin poly(L-lactic acid-iconic acid N-diol) (P(LA-NI)) copolymer films were developed using a "one-step" polycondensation process with integrated toughness, barrier properties, gas selectivity, and quality control features. The massive branched structure and gg conformers in P(LA-NI) act as "internal chain expansion" and "internal plasticization". Meanwhile, P(LA-NI) contains numerous polar groups and unique nanoscale microphase structures to realize excellent CO2, O2 barrier, CO2/O2 selectivity, anti-fogging, and UV shielding functions. The atmosphere within the package spontaneously achieves the desirable low O2 and high CO2 levels when packaging button mushrooms with high respiratory metabolism. Eventually, the shelf life of button mushrooms reached 24 days, >3-fold extended. This PLLA-based film meets "dual carbon" and "food safety" goals and has vast potential for fresh food preservation.

CPPs-modified chitosan as permeability-enhancing chemotherapeutic combined with gene therapy nanosystem by thermosensitive hydrogel for the treatment of osteosarcoma.

BACKGROUND: Chemotherapy resistance of osteosarcoma (OS) is still the crux of poor clinical curative effect.E3 ubiquitin-protein ligase Rad18 (Rad18) contributed to doxorubicin resistance in OS, which ultimately mediated DNA damage tolerance and led to a poor prognosis and chemotherapy response in patients. METHODS: In this study, doxorubicin was loaded in the process of Fe2+ and siRad18 forming nanoparticles(FSD) through coordination, chitosan modified with cell penetrating peptide (H6R6) was synthesized and coated on the surface of the NPs(FSD-CHR). FSD-CHR was then dispersed in thermosensitive hydrogel(PPP) for peritumoral injection of osteosarcoma in situ. Subsequently, the physicochemical properties and molecular biological characteristics of the drug delivery system were characterized. Finally, an osteosarcoma model was established to study the anti-tumor effects of multifunctional nanoparticles and the immunotherapy effect combined with αPD-L1. RESULTS: FSD-CHR has enhanced tumor tissue permeability, siRad18 can significantly reduce Dox-mediated DNA damage tolerance and enhance anti-tumor effects, and iron-based NPs show enhanced ROS upregulation. FSD-CHR@PPP showed significant inhibition of osteosarcoma growth in vivo and a reduced incidence of lung metastasis. In addition, siRad18 was unexpectedly found to enhance Dox-mediated immunogenic cell death (ICD).FSD-CHR@PPP combined with PD-L1 blocking significantly enhanced anti-tumor effects due to decreased PD-L1 enrichment. CONCLUSION: Hydrogel encapsulation of permeable nanoparticles provides an effective strategy for doxorubicin-resistant OS, showing that gene therapy blocking DNA damage tolerance can enhance treatment response to chemotherapy and appears to enhance the effect of ICD inducers to activate the immune system.

Konjac glucomannan films incorporated pectin-stabilized Mandarin oil emulsions: Structure, properties, and application in fruit preservation.

To enhance the water-resistance and antibacterial properties of KGM films, mandarin oil (MO), was directly emulsified by pectin and then dispersed to the KGM matrix. The effect of MO concentration (0, 0.5, 1.0, 1.5, and 2 wt%) on the performance of the film-forming emulsions as well as the emulsion films was investigated. The results revealed that pectin could encapsulate and protect MO, and KGM as film matrix could further contributed to the high stability of the film-forming emulsions. The FT-IR, XRD, and SEM suggested that MO stabilized by pectin was uniformly distributed in the KGM matrix. The compatibility and good interaction between KGM and pectin contributed to highly dense and compact structure. Furthermore, increasing the concentration of MO effectively improved water-resistance, oxygen barrier, and antimicrobial activity of the KGM based films. The 1.5 wt% MO loaded KGM film had the highest tensile strength (72.22 MPa) and water contact angle (θ = 95.73°), reduced the WVP and oxygen permeability by about 25.8 % and 32.8 times, respectively, prolonged the shelf life of strawberries for 8 days. As demonstrated, the 1.5 wt% MO-loaded KGM film has considerable potential for high-performance natural biodegradable active films to ensure food safety and reduce environmental impacts.

Delivery of miR-29a improves the permeability of cisplatin by downregulating collagen I expression.

In the clinical setting, chemotherapy is the most widely used antitumor treatment, however, chemotherapy resistance significantly limits its efficacy. Reduced drug influx is a key mechanism of chemoresistance, and inhibition of the complexity of the tumor microenvironment (TME) may improve chemotherapy drug influx and therapeutic efficiency. In the current study, we identified that the major extracellular matrix protein collagen I is more highly expressed in lung cancer tissues than adjacent tissues in patients with lung cancer. Furthermore, Kaplan-Meier analysis suggested that COL1A1 expression was negatively correlated with the survival time of patients with lung cancer. Our previous study demonstrated that miR-29a inhibited collagen I expression in lung fibroblasts. Here, we investigated the effect of miR-29a on collagen I expression and the cellular behavior of lung cancer cells. Our results suggest that transfection with miR-29a could prevent Lewis lung carcinoma (LLC) migration by downregulating collagen I expression, but did not affect the proliferation, apoptosis, and cell cycle of LLC cells. In a 3D tumoroid model, we demonstrated that miR-29a transfection significantly increased cisplatin (CDDP) permeation and CDDP-induced cell death. Furthermore, neutral lipid emulsion-based miR-29a delivery improved the therapeutic effect of cisplatin in an LLC spontaneous tumor model in vivo. In summary, this study shows that targeting collagen I expression in the TME contributes to chemotherapy drug influx and improves therapeutic efficacy in lung cancer.

Sclareol protected against intestinal barrier dysfunction ameliorating Crohn's disease-like colitis via Nrf2/NF-B/MLCK signalling.

BACKGROUND: Inflammation-induced intestinal barrier dysfunction is not only a pathological feature of Crohn's disease (CD) but also an important therapeutic target. Sclareol (SCL) is a nontoxic natural plant compound with anti-inflammatory effect, but its role in CD has not been established. METHODS: In vivo studies of mice with TNBS-induced colitis were carried out to evaluate the effects of SCL on CD-like colitis and intestinal barrier function. In vitro, a TNF-α-induced colonic organoid model was established to test the direct effect of SCL on inflammation-induced intestinal barrier injure and inflammatory response. The Nrf2/NF-κB/MLCK signalling was analysed to explore the mechanism of SCL. RESULTS: In vivo, SCL largely alleviated the colitis in TNBS mice, as evidenced by improvements in the weight loss, colitis symptoms, endoscopic score, macroscopic histological score, and histological inflammation score. Moreover, SCL significantly improved intestinal barrier dysfunction, manifested as reduced intestinal permeability and decreased intestinal bacterial translocation in TNBS mice. Importantly, SCL antagonised the intestinal mucosal inflammation while protecting tight junctions in TNBS mice. In vitro, SCL largely depressed pro-inflammatory cytokines levels and improved intestinal epithelial permeability in a TNF-α-induced colonic organoid model. In the context of CD, the protective effects of SCL against inflammation and intestinal barrier damage are at least partially results from the Nrf2 signalling activation and the NF-κB/MLCK signalling inhibition. CONCLUSIONS: SCL improved intestinal barrier dysfunction and alleviated CD-like colitis, possibly through modulation of Nrf2/NF-κB/MLCK signalling. In view of SCL's safety profile, there is hope that it will be useful in the clinic.

The Celiac-Disease Superantigen Oligomerizes and Increases Permeability in an Enterocyte Cell Model.

Celiac disease (CeD) is an autoimmune disorder triggered by gluten proteins, affecting approximately 1 % of the global population. The 33-mer deamidated gliadin peptide (DGP) is a metabolically modified wheat-gluten superantigen for CeD. Here, we demonstrate that the 33-mer DGP spontaneously assembles into oligomers with a diameter of approximately 24 nm. The 33-mer DGP oligomers present two main secondary structural motifs-a major polyproline II helix and a minor ß-sheet structure. Importantly, in the presence of 33-mer DGP oligomers, there is a statistically significant increase in the permeability in the gut epithelial cell model Caco-2, accompanied by the redistribution of zonula occludens-1, a master tight junction protein. These findings provide novel molecular and supramolecular insights into the impact of 33-mer DGP in CeD and highlight the relevance of gliadin peptide oligomerization.