Decanedioic acid

pH/Glucose Dual Responsive Metformin Release Hydrogel Dressings with Adhesion and Self-Healing via Dual-Dynamic Bonding for Athletic Diabetic Foot Wound Healing

In view of the lack of a specific drug-sustained release system that is responsive to chronic wounds of the type II diabetic foot, and the demands for frequent movement at the foot wound, pH/glucose dual-responsive metformin-released adhesion-enhanced self-healing easy-removable antibacterial antioxidant conductive hemostasis multifunctional phenylboronic acid and benzaldehyde bifunctional polyethylene glycol-co-poly(glycerol sebacic acid)/dihydrocaffeic acid and l-arginine cografted chitosan (PEGS-PBA-BA/CS-DA-LAG, denoted as PC) hydrogel dressings were constructed based on the double dynamic bond of the Schiff-base and phenylboronate ester. It was further demonstrated that the PC hydrogel promotes wound healing by reducing inflammation and enhancing angiogenesis in a rat type II diabetic foot model. In addition, the addition of metformin (Met) and graphene oxide (GO), as well as their synergy, were confirmed to better promote wound repair in vivo. In summary, adhesion-enhanced self-healing multifunctional PC/GO/Met hydrogels with stimuli-responsive metformin release ability and easy removability have shown a promoting effect on the healing of chronic athletic diabetic wounds and provide a local-specific drug dual-response release strategy for the treatment of type II diabetic feet.

Chitosan-based multifunctional flexible hemostatic bio-hydrogel

Realizing the potential application of chitosan as an effective biomedical hemostatic agent has become an emerging research hotspot. However, fabricating a flexible chitosan-based hemostatic bio-hydrogel with self-adhesion feature in humid conditions and rapid hemostasis capability remains a challenge. Herein, we reported the development of chitosan-based hydrogels (DCS-PEGSH gels) with typical multilevel pore structures, which were cross-linked by 3-(3,4-dihydroxyphenyl) propionic acid-modified chitosan (DCS) and sebacic acid-terminated polyethylene glycol modified by p-hydroxybenzaldehyde (PEGSH). By precisely regulating the proportion of PEGSH, the fabricated bio-hydrogels displayed favorable cytocompatibility, suitable stretchability (?780%), and blood absorbability (1300% ± 50%). Moreover, the strong adhesion (?68.5 kPa) of the assembled bio-hydrogel ensured its firm adherence on pigskin and on bleeding wound in both static and dynamic humid environments without shedding, thus providing a long service life. The fabricated hydrogels exhibited shorter blood clotting time (50 s) and lower blood clotting index (BCI, 41) than the commercial chitosan sponge (288 s, BCI 65). Notably, the amount of blood loss from the liver in mice was reduced by almost 90% as compared to that for the control group. This study paves a solid way for developing a chitosan-based hydrogel with self-adhesive, self-healing, stretchability, biocompatibility, and antibacterial and antioxidant properties through molecular design and structural regulation, which will enable the biomedical application of chitosan in emergency hemostasis, particularly in joints and extremities. STATEMENT OF SIGNIFICANCE: The design and preparation of multifunctional integrated green adhesive bio-hydrogels while avoiding the use of organic solvents and toxic chemical reagents has been an emerging challenge. Herein, a flexible chitosan-based hemostatic bio-hydrogel that integrates multifunctional properties was successfully synthesized. The bio-hydrogel displayed suitable stretchability (780%) and blood absorbability (1300% ± 50%). Moreover, the strong adhesion (68.5 kPa) ensured firm adherence of the assembled hydrogel on pigskin and on the bleeding wound site in both static and dynamic humid environments without shedding, thus providing a long service life. In addition, the designed hydrogel showed good compatibility and antibacterial performance. The dynamic Schiff base endowed the bio-hydrogel with excellent self-healing performance without any external stimuli.

Dietary fruit and vegetable intake, gut microbiota, and type 2 diabetes: results from two large human cohort studies

Background: Little is known about the inter-relationship among fruit and vegetable intake, gut microbiota and metabolites, and type 2 diabetes (T2D) in human prospective cohort study. The aim of the present study was to investigate the prospective association of fruit and vegetable intake with human gut microbiota and to examine the relationship between fruit and vegetable-related gut microbiota and their related metabolites with type 2 diabetes (T2D) risk.
Methods: This study included 1879 middle-age elderly Chinese adults from Guangzhou Nutrition and Health Study (GNHS). Baseline dietary information was collected using a validated food frequency questionnaire (2008-2013). Fecal samples were collected at follow-up (2015-2019) and analyzed for 16S rRNA sequencing and targeted fecal metabolomics. Blood samples were collected and analyzed for glucose, insulin, and glycated hemoglobin. We used multivariable linear regression and logistic regression models to investigate the prospective associations of fruit and vegetable intake with gut microbiota and the association of the identified gut microbiota (fruit/vegetable-microbiota index) and their related fecal metabolites with T2D risk, respectively. Replications were performed in an independent cohort involving 6626 participants.
Results: In the GNHS, dietary fruit intake, but not vegetable, was prospectively associated with gut microbiota diversity and composition. The fruit-microbiota index (FMI, created from 31 identified microbial features) was positively associated with fruit intake (p < 0.001) and inversely associated with T2D risk (odds ratio (OR) 0.83, 95%CI 0.71-0.97). The FMI-fruit association (p = 0.003) and the FMI-T2D association (OR 0.90, 95%CI 0.84-0.97) were both successfully replicated in the independent cohort. The FMI-positive associated metabolite sebacic acid was inversely associated with T2D risk (OR 0.67, 95%CI 0.51-0.86). The FMI-negative associated metabolites cholic acid (OR 1.35, 95%CI 1.13-1.62), 3-dehydrocholic acid (OR 1.30, 95%CI 1.09-1.54), oleylcarnitine (OR 1.77, 95%CI 1.45-2.20), linoleylcarnitine (OR 1.66, 95%CI 1.37-2.05), palmitoylcarnitine (OR 1.62, 95%CI 1.33-2.02), and 2-hydroglutaric acid (OR 1.47, 95%CI 1.25-1.72) were positively associated with T2D risk.
Conclusions: Higher fruit intake-associated gut microbiota and metabolic alteration were associated with a lower risk of T2D, supporting the public dietary recommendation of adopting high fruit intake for the T2D prevention.

Insecticidal, Antimalarial, and Antileishmanial Effects of Royal Jelly and Its Three Main Fatty Acids, trans-10-Hydroxy-2-decenoic Acid, 10-Hydroxydecanoic Acid, and Sebacic Acid

Natural products and their derivatives as an inexpensive, accessible, and useful alternative medicine are broadly applied for the treatment of a wide range of diseases and infectious ones. The present study was designed to evaluate the insecticidal, antimalarial, antileishmanial, and cytotoxic effects of royal jelly and its three main fatty acids (trans-10-hydroxy-2-decenoic acid (10-H2DA), 10-hydroxydecanoic acid (10-HDAA), sebacic acid (1,10-decanedioic acid)). Insecticidal activity of RJ and 10-H2DA, 10-HDAA, and sebacic acid was performed against healthy 4th instar larvae at 25 ± 2°C. Antiplasmodial and antileishmanial effects of RJ and 10-H2DA, 10-HDAA, and sebacic acid were also performed against chloroquine-resistant Plasmodium falciparum K1-strain and Leishmania major amastigotes according to the Malstat method and macrophage model, respectively. In addition, the level of nitric oxide (NO) production in J774-A1 macrophages cells, plasma membrane permeability, and caspase-3-like activity and cytotoxicity effects of RJ and 10-H2DA, 10-HDAA, and sebacic acid against human embryonic kidney 293 (HEK239T cells) were evaluated. Considering the insecticidal activity, the results showed that the lethal concentration 50% value for RJ, 10-H2DA, 10-HDAA, and sebacic acid was 24.6, 31.4, 37.8, and 44.7 μg/mL μg/mL, respectively. RJ, 10-H2DA, 10-HDAA, and sebacic acid showed potent (P < 0.0001) antileishmanial effects with IC₅₀ values ranging from 2.4 to 8.4 μg/mL. Various concentrations of RJ, 10-H2DA, 10-HDAA, and sebacic acid significantly (P < 0.05) increased the production of NO, plasma membrane permeability, and caspase-3-like activity level as a dose-dependent response. Considering the cytotoxicity, SIs > 10 of these compounds exhibited their specificity to parasites and safety against human HEK239T normal cells. The results of the present investigation revealed the promising insecticidal, antimalarial, and antileishmanial effects of RJ and its three main fatty acids (10-H2DA, 10-HDAA, and sebacic acid). However, more studies are required to confirm the mechanisms of action mode of these compounds as well as their efficacy in animal models and clinical settings.

A review of existing strategies for designing long-acting parenteral formulations: Focus on underlying mechanisms, and future perspectives

The need for long-term treatments of chronic diseases has motivated the widespread development of long-acting parenteral formulations (LAPFs) with the aim of improving drug pharmacokinetics and therapeutic efficacy. LAPFs have been proven to extend the half-life of therapeutics, as well as to improve patient adherence; consequently, this enhances the outcome of therapy positively. Over past decades, considerable progress has been made in designing effective LAPFs in both preclinical and clinical settings. Here we review the latest advances of LAPFs in preclinical and clinical stages, focusing on the strategies and underlying mechanisms for achieving long acting. Existing strategies are classified into manipulation of in vivo clearance and manipulation of drug release from delivery systems, respectively. And the current challenges and prospects of each strategy are discussed. In addition, we also briefly discuss the design principles of LAPFs and provide future perspectives of the rational design of more effective LAPFs for their further clinical translation.