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Pharmaceutics May 2024A general procedure to prepare gold nanourchins (GNUs) via a seed-mediated method was followed using dopamine hydrochloride as a reducing agent and silver nitrate salt...
A general procedure to prepare gold nanourchins (GNUs) via a seed-mediated method was followed using dopamine hydrochloride as a reducing agent and silver nitrate salt (AgNO) as a shape-directing agent. The novelty of this study comes from the successful incorporation of the prepared gold urchins as an aqueous suspension in a nasal pressurized metered dose inhaler (pMDI) formulation and the investigation of their potential for olfactory targeting for direct nose-to-brain drug delivery (NTBDD). The developed pMDI formulation was composed of 0.025% / GNUs, 2% / Milli-Q water, and 2% / EtOH, with the balance of the formulation being HFA134a propellant. Particle integrity and aerosolization performance were examined using an aerosol exposure system, whereas the nasal deposition profile was tested in a sectioned anatomical replica of human nasal airways. The compatibility of the gold dispersion with the nasal epithelial cell line RPMI 2650 was also investigated in this study. Colloidal gold was found to be stable following six-month storage at 4 °C and during the lyophilization process utilizing a pectin matrix for complete re-dispersibility in water. The GNUs were intact and discrete following atomization via a pMDI, and 13% of the delivered particles were detected beyond the nasal valve, the narrowest region in the nasal cavity, out of which 5.6% was recovered from the olfactory region. Moreover, the formulation was found to be compatible with the human nasal epithelium cell line RPMI 2650 and excellent cell viability was observed. The formulated GNU-HFA-based pMDI is a promising approach for intranasal drug delivery, including deposition in the olfactory region, which could be employed for NTBDD applications.
PubMed: 38794331
DOI: 10.3390/pharmaceutics16050669 -
BMC Cancer May 2024Breast cancer patients often have a poor prognosis largely due to lack of effective targeted therapy. It is now well established that monosaccharide enhances growth...
Breast cancer patients often have a poor prognosis largely due to lack of effective targeted therapy. It is now well established that monosaccharide enhances growth retardation and chemotherapy sensitivity in tumor cells. However, Pectinose whether has capability to restrict the proliferation of tumor cells remain unclear. Here, we report that Pectinose induced cytotoxicity is modulated by autophagy and p38 MAPK signaling pathway in breast cancer cell lines. The proliferation of cells was dramatically inhibited by Pectinose exposure in a dose-dependent manner, which was relevant to cell cycle arrest, as demonstrated by G2/M cell cycle restriction and ectopic expression of Cyclin A, Cyclin B, p21and p27. Mechanistically, we further identified that Pectinose is positively associated with autophagy and the activation of the p38 MAPK signaling in breast cancer. In contrast, 3-Ma or SB203580, the inhibitor of autophagy or p38 MAPK, reversed the efficacy of Pectinose suppressing on breast cancer cell lines proliferation and cell cycle process. Additionally, Pectinose in vivo treatment could significantly inhibit xenograft growth of breast cancer cells. Taken together, our findings were the first to reveal that Pectinose triggered cell cycle arrest by inducing autophagy through the activation of p38 MAPK signaling pathway in breast cancer cells,especially in luminal A and triple-negative breast cancer.
Topics: Humans; Autophagy; Female; Animals; Triple Negative Breast Neoplasms; p38 Mitogen-Activated Protein Kinases; Pectins; Mice; Cell Cycle Checkpoints; Cell Line, Tumor; Cell Proliferation; Xenograft Model Antitumor Assays; MAP Kinase Signaling System
PubMed: 38789954
DOI: 10.1186/s12885-024-12293-8 -
Chemosphere May 2024Perfluorooctanesulfonic acid (PFOS) is a widely recognized environment pollutant known for its high bioaccumulation potential and a long elimination half-life. Several...
Perfluorooctanesulfonic acid exposure leads to downregulation of 3-hydroxy-3-methylglutaryl-CoA synthase 2 expression and upregulation of markers associated with intestinal carcinogenesis in mouse intestinal tissues.
Perfluorooctanesulfonic acid (PFOS) is a widely recognized environment pollutant known for its high bioaccumulation potential and a long elimination half-life. Several studies have shown that PFOS can alter multiple biological pathways and negatively affect human health. Considering the direct exposure to the gastrointestinal (GI) tract to environmental pollutants, PFOS can potentially disrupt intestinal homeostasis. However, there is limited knowledge about the effect of PFOS exposure on normal intestinal tissues, and its contribution to GI-associated diseases remains to be determined. In this study, we examined the effect of PFOS exposure on the gene expression profile of intestinal tissues of C57BL/6 mice using RNAseq analysis. We found that PFOS exposure in drinking water significantly downregulates mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase 2 (HMGCS2), a rate-limiting ketogenic enzyme, in intestinal tissues of mice. We found that diets containing the soluble fibers inulin and pectin, which are known to be protective against PFOS exposure, were ineffective in reversing the downregulation of HMGCS2 expression in vivo. Analysis of intestinal tissues also demonstrated that PFOS exposure leads to upregulation of proteins implicated in colorectal carcinogenesis, including β-catenin, c-MYC, mTOR and FASN. Consistent with the in vivo results, PFOS exposure leads to downregulation of HMGCS2 in mouse and human normal intestinal organoids in vitro. Furthermore, we show that shRNA-mediated knockdown of HMGCS2 in a human normal intestinal cell line resulted in increased cell proliferation and upregulation of key proliferation-associated proteins such as cyclin D, survivin, ERK1/2 and AKT, along with an increase in lipid accumulation. In summary, our results suggest that PFOS exposure may contribute to pathological changes in normal intestinal cells via downregulation of HMGCS2 expression and upregulation of pro-carcinogenic signaling pathways that may increase the risk of colorectal cancer development.
PubMed: 38754493
DOI: 10.1016/j.chemosphere.2024.142332 -
JGH Open : An Open Access Journal of... May 2024To evaluate the efficacy and safety of minocycline, vonoprazan, amoxicillin, and bismuth quadruple therapy for () treatment.
BACKGROUND AND AIM
To evaluate the efficacy and safety of minocycline, vonoprazan, amoxicillin, and bismuth quadruple therapy for () treatment.
METHODS
From August 2022 to May 2023, clinical data were collected from patients who received eradication treatment at West China Fourth Hospital, Sichuan University. One group received the MVAB regimen (amoxicillin, minocycline, vonoprazan, and colloidal bismuth pectin), while another group received the FOAB regimen (amoxicillin, furazolidone, omeprazole, and colloidal bismuth pectin), both administered for 14 days. Follow-up assessments of safety and compliance were conducted within 1 week after treatment completion. One and a half months after treatment, the success of eradication was evaluated using the urea breath test.
RESULTS
For the MVAB regimen as a first-line treatment, the eradication rate was 90.1% (127/141, 95% CI: 85.1-95.1%) in the ITT analysis and 93.4% (127/136, 95% CI: 89.2-97.6%) in the PP analysis as a first-line treatment. As a second-line treatment, the eradication rate was 91.3% (21/23, 95% CI: 78.8-103.8%) in both analyses. For the FOAB regimen as a first-line treatment, the eradication rate was 98.0% (50/51, 95% CI: 94.1-101.2%) in the ITT analysis and 100% (50/50, 95% CI: 100%) in the PP analysis. As a second-line treatment, the eradication rate was 100% (6/6, 95% CI: 100%) in both analyses. Moreover, there was no significant difference in the incidence of adverse events between the two groups (MVAB regimen: 5.5% and FOAB regimen: 8.8%; > 0.05).
CONCLUSIONS
The MVAB regimen could indeed be a viable alternative treatment option to conventional therapies.
PubMed: 38699469
DOI: 10.1002/jgh3.13070 -
Current Biology : CB May 2024Xyloglucan is believed to play a significant role in cell wall mechanics of dicot plants. Surprisingly, Arabidopsis plants defective in xyloglucan biosynthesis exhibit...
Xyloglucan is believed to play a significant role in cell wall mechanics of dicot plants. Surprisingly, Arabidopsis plants defective in xyloglucan biosynthesis exhibit nearly normal growth and development. We investigated a mutant line, cslc-Δ5, lacking activity in all five Arabidopsis cellulose synthase like-C (CSLC) genes responsible for xyloglucan backbone biosynthesis. We observed that this xyloglucan-deficient line exhibited reduced cellulose crystallinity and increased pectin levels, suggesting the existence of feedback mechanisms that regulate wall composition to compensate for the absence of xyloglucan. These alterations in cell wall composition in the xyloglucan-absent plants were further linked to a decrease in cell wall elastic modulus and rupture stress, as observed through atomic force microscopy (AFM) and extensometer-based techniques. This raised questions about how plants with such modified cell wall properties can maintain normal growth. Our investigation revealed two key factors contributing to this phenomenon. First, measurements of turgor pressure, a primary driver of plant growth, revealed that cslc-Δ5 plants have reduced turgor, preventing the compromised walls from bursting while still allowing growth to occur. Second, we discovered the conservation of elastic asymmetry (ratio of axial to transverse wall elasticity) in the mutant, suggesting an additional mechanism contributing to the maintenance of normal growth. This novel feedback mechanism between cell wall composition and mechanical properties, coupled with turgor pressure regulation, plays a central role in the control of plant growth and is critical for seedling establishment in a mechanically challenging environment by affecting shoot emergence and root penetration.
Topics: Cell Wall; Glucans; Xylans; Arabidopsis; Seedlings; Arabidopsis Proteins; Glucosyltransferases; Cellulose
PubMed: 38677280
DOI: 10.1016/j.cub.2024.04.016 -
International Journal of Biological... May 2024Enzymatic degradation of plant biomass requires the coordinated action of various enzymes. In this study, the production of reducing sugars from pectic substrates and...
Enzymatic degradation of plant biomass requires the coordinated action of various enzymes. In this study, the production of reducing sugars from pectic substrates and sugar beet pulp (SBP) was investigated and compared using commercial enzyme preparations, including M2, pectinase (E1), Viscozyme L (V-L) and L-40. V-L, a cellulolytic enzyme mix produced by Aspergillus sp. was further evaluated as the most robust enzyme cocktail with the strongest SBP degradation ability in terms of the release of monosaccharides, methanol, and acetate from SBP. Mass-spectrometry-based proteomics analysis of V-L revealed 156 individual proteins. Of these, 101 proteins were annotated as containing a carbohydrate-active enzyme module. Notably, of the 50 most abundant proteins, ca. 44 % were predicted to be involved in pectin degradation. To reveal the role of individual putative key enzymes in pectic substrate decomposition, two abundant galacturonases (PglA and PglB), were heterologously expressed in Pichia pastoris and further characterized. PglA and PglB demonstrated maximum activity at 57 °C and 68 °C, respectively, and exhibited endo-type cleavage patterns towards polygalacturonic acid. Further studies along this line may lead to a better understanding of efficient SBP degradation and may help to design improved artificial enzyme mixtures with lower complexity for future application in biotechnology.
Topics: Pectins; Proteomics; Substrate Specificity; Polygalacturonase; Beta vulgaris; Aspergillus
PubMed: 38580019
DOI: 10.1016/j.ijbiomac.2024.131309 -
Gastrointestinal Endoscopy Mar 2024Traction has become the reference strategy for colorectal endoscopic submucosal dissection (ESD). One of its major limitations is that the force of traction decreases as...
BACKGROUND AND AIMS
Traction has become the reference strategy for colorectal endoscopic submucosal dissection (ESD). One of its major limitations is that the force of traction decreases as dissection progresses. The ATRACT traction device uses a pulley system to increase traction during the procedure, making it easier and faster. A retrospective study of 54 cases showed interesting results in terms of efficacy and safety throughout the digestive tract. We sought to confirm these initial results with a prospective study of resections of colorectal lesions.
METHODS
In this prospective multicenter study, 5 experienced operators from 3 different centers each performed 10 procedures using the ATRACT device consecutively for all conventional colorectal ESDs measuring between 4 and 10 cm in conventional locations (no recurrent lesions, appendicular, of the ileo-cecal valve, in contact with the pectinate line or measuring more than 2/3 of the circumference).
RESULTS
Between November 2022 and April 2023, 50 ESDs were performed in 49 patients. On average, the main diameter of the lesions was 66.6 mm, with a surface area of 3066 mm2. The mean operating time was 55.2 minutes, resulting in a mean resection speed of 61.4 mm2/min. En Bloc and R0 resection rates were 100% and 98% respectively. Resections were curative in 94% of cases. 4 perforations (8%) occurred, all of which were closed endoscopically without the need for surgery. 1 case of delayed hemorrhage (2%) was noted. To date, this is the series with the highest resection speeds in the literature for colorectal ESD. For comparison, Yamamoto et al. reported a speed of 23.5 mm2/min using the "pocket" strategy and Bordillon et al. reported a speed of 39.1 mm2/min using the double-clip traction technique. These results need to be confirmed in larger studies, and in non-expert centers.
CONCLUSIONS
This prospective evaluation confirms the efficacy and safety of the adaptive traction strategy with the ATRACT device for colorectal ESD with high resection speed.
PubMed: 38458261
DOI: 10.1016/j.gie.2024.02.032 -
Cells Feb 2024In this study, we investigated the beneficial effects of grapefruit IntegroPectin, derived from industrial waste grapefruit peels via hydrodynamic cavitation, on...
In this study, we investigated the beneficial effects of grapefruit IntegroPectin, derived from industrial waste grapefruit peels via hydrodynamic cavitation, on microglia cells exposed to oxidative stress conditions. Grapefruit IntegroPectin fully counteracted cell death and the apoptotic process induced by cell exposure to tert-butyl hydroperoxide (TBH), a powerful hydroperoxide. The protective effects of the grapefruit IntegroPectin were accompanied with a decrease in the amount of ROS, and were strictly dependent on the activation of the phosphoinositide 3-kinase (PI3K)/Akt cascade. Finally, IntegroPectin treatment inhibited the neuroinflammatory response and the basal microglia activation by down-regulating the PI3K- nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB)- inducible nitric oxide synthase (iNOS) cascade. These data strongly support further investigations aimed at exploring IntegroPectin's therapeutic role in in vivo models of neurodegenerative disorders, characterized by a combination of chronic neurodegeneration, oxidative stress and neuroinflammation.
Topics: Humans; Microglia; Citrus paradisi; Phosphatidylinositol 3-Kinases; Anti-Inflammatory Agents; Cell Line
PubMed: 38391968
DOI: 10.3390/cells13040355 -
Toxicology Research Feb 2024The safety of a rhamnogalacturonan-I-enriched pectin extract (G3P-01) from pumpkin ( var. Dickinson) was evaluated for use as an ingredient in food and dietary...
The safety of a rhamnogalacturonan-I-enriched pectin extract (G3P-01) from pumpkin ( var. Dickinson) was evaluated for use as an ingredient in food and dietary supplements. G3P-01 was tested in a battery of genetic toxicity studies including reverse mutagenicity and micronucleus assay. In addition, Sprague-Dawley rats were randomized and orally dosed with G3P-01 incorporated in animal diet at concentrations of 0, 9000, 18,000, and 36,000 ppm daily for 13-weeks (n=10/sex/group) in line with OECD guidelines (TG 408). The results of the bacterial reverse mutation assay and micronucleus assay in TK6 cells demonstrated a lack of genotoxicity. The 13-week oral toxicity study in Sprague-Dawley rats demonstrated that the test article, G3P-01 was well tolerated; there were no mortalities and no adverse effects on clinical, gross pathology, hematology, blood chemistry, and histological evaluation of the essential organs of the animals. The present study demonstrates that G3P-01 is non-genotoxic and is safe when ingested in diet at concentrations up to 36, 000 ppm. The subchronic no-observed-adverse-effect level (NOAEL) for G3P-01 was concluded to be 36,000 ppm, equivalent to 1,899 and 2,361 mg/kg/day for male and female rats respectively.
PubMed: 38274036
DOI: 10.1093/toxres/tfae004 -
Pharmaceutics Jan 2024Traditional wound dressings may lack suitability for diverse wound types and individual patient requirements. In this context, this study aimed to innovate wound care by...
3D-Printed Alginate/Pectin-Based Patches Loaded with Olive Leaf Extracts for Wound Healing Applications: Development, Characterization and In Vitro Evaluation of Biological Properties.
Traditional wound dressings may lack suitability for diverse wound types and individual patient requirements. In this context, this study aimed to innovate wound care by developing a 3D-printed patch using alginate and pectin and incorporating Olive Leaf Extract (OLE) as an active ingredient. Different polymer-to-plasticizer ratios were systematically examined to formulate a printable ink with optimal viscosity. The resultant film, enriched with OLE, exhibited a substantial polyphenolic content of 13.15 ± 0.41 mg CAE/g, showcasing significant antioxidant and anti-inflammatory properties. Notably, the film demonstrated potent scavenging abilities against DPPH, ABTS, and NO radicals, with IC values of 0.66 ± 0.07, 0.47 ± 0.04, and 2.02 ± 0.14 mg/mL, respectively. In vitro release and diffusion studies were carried out and the release profiles revealed an almost complete release of polyphenols from the patch within 48 h. Additionally, the fabricated film exhibited the capacity to enhance cell motility and accelerate wound healing, evidenced by increased collagen I expression in BJ fibroblast cells. Structural assessments affirmed the ability of the patch to absorb exudates and maintain the optimal moisture balance, while biocompatibility studies underscored its suitability for biomedical applications. These compelling findings endorse the potential application of the developed film in advanced wound care, with the prospect of tailoring patches to individual patient needs.
PubMed: 38258109
DOI: 10.3390/pharmaceutics16010099