Tannic acid modified keratin/sodium alginate/carboxymethyl chitosan biocomposite hydrogels with good mechanical properties and swelling behavior.

Natural polymer-based hydrogels have demonstrated great potential as wound-healing dressings. They help to maintain a moist wound environment as well as promote faster healing. In this work, a multifunctional hydrogel was prepared using keratin, sodium alginate, and carboxymethyl chitosan with tannic acid modification. Micro-morphology of hydrogels has been performed by scanning electron microscopy. Fourier Transform Infrared Spectroscopy reveals the presence of hydrogen bonding. The mechanical properties of the hydrogels were examined using a universal testing machine. Furthermore, we investigated several properties of the modified hydrogel. These properties include swelling rate, water retention, anti-freezing properties, antimicrobial and antioxidant properties, hemocompatibility evaluation and cell viability test in vitro. The modified hydrogel has a three-dimensional microporous structure, the swelling rate was 1541.7%, the elastic modulus was 589.74 kPa, the toughness was 211.74 kJ/m3, and the elongation at break was 75.39%, which was similar to the human skin modulus. The modified hydrogel also showed inhibition of S. aureus and E. coli, as well as a DPPH scavenging rate of 95%. In addition, the modified hydrogels have good biological characteristics. Based on these findings, the K/SA/CCS hydrogel holds promise for applications in biomedical engineering.

Pectin forms polymeric pigments by complexing anthocyanins during red winemaking and ageing.

The long-term stability of red wine color depends on the formation of polymeric pigments from anthocyanins. Although there is still a lot of uncertainty about the specific structure of this diverse group of pigments, there is consensus that they are reaction products of anthocyanins and other polyphenols. Interactions between anthocyanins and pectic polysaccharides have been suggested to stabilize anthocyanins. This study explores the impact of such interactions by adding pectin during red winemaking. The results demonstrate that these interactions induce the formation of additional polymeric pigments which enhance the pigment stability during fermentation and aging. While initial pigment formation is higher in wines with added pectin, a notable proportion of the complexes degrades in the later stages of fermentation. Presumably, tannins form insoluble complexes with pectin, reducing tannin concentration by more than 300 mg/L. Anthocyanin concentrations decrease by over 400 mg/L, and polymeric pigments double. Anthocyanins that form polymeric pigments with pectic polysaccharides expand the range of pigments in red wines with possible consequences for the sensory properties of the wine. These findings highlight the complex interactions between pectin, anthocyanins, and tannins, and their influence on pigment formation and wine composition during fermentation and aging.

Borate bonds-containing pH-responsive chitosan hydrogel for postoperative tumor recurrence and wound infection prevention.

Chitosan has been widely used in biomedical fields due to its good antibacterial properties, excellent biocompatibility, and biodegradability. In this study, a pH-responsive and self-healing hydrogel was synthesized from 3-carboxyphenylboronic acid grafted with chitosan (CS-BA) and polyvinyl alcohol (PVA). The dynamic boronic ester bonds and intermolecular hydrogen bonds are responsible for the hydrogel formation. By changing the mass ratio of CS-BA and PVA, the tensile stress and compressive stress of hydrogel can controlled in the range of 0.61 kPa - 0.74 kPa and 295.28 kPa - 1108.1 kPa, respectively. After doping with tannic acid (TA)/iron nanocomplex (TAFe), the hydrogel successful killed tumor cells through the near infrared laser-induced photothermal conversion and the TAFe-triggered reactive oxygen species generation. Moreover, the photothermal conversion of the hydrogel and the antibacterial effect of CS and TA give the hydrogel a good antibacterial effect. The CS-BA/PVA/TAFe hydrogel exhibit good in vivo and in vitro anti-tumor recurrence and antibacterial ability, and therefore has the potential to be used as a powerful tool for the prevention of local tumor recurrence and bacterial infection after surgery.

Battling Salmonella enteritidis infections: integrating proteomics and in vivo assessment of Galla Chinensis tannic acid.

Salmonella infections pose a significant threat to animal and human health. Phytochemicals present a potential alternative treatment. Galla chinensis tannic acid (GCTA), a hydrolyzable polyphenolic compound, inhibits bacterial growth and demonstrates potential as an alternative or supplement to antibiotics to prevent Salmonella infections. However, little is known about the antimicrobial mechanism of GCTA against Salmonella. Here, we revealed 456 differentially expressed proteins upon GCTA treatment, impacting pathways related to DNA replication, repair, genomic stability, cell wall biogenesis, and lipid metabolism using TMT-labeled proteomic analysis. TEM analysis suggested altered bacterial morphology and structure post-treatment. A Salmonella-infected-mouse model indicated that GCTA administration improved inflammatory markers, alleviated intestinal histopathological alterations, and reduced Salmonella enterica serovar Enteritidis (S. Enteritidis) colonization in the liver and spleen of Salmonella-infected mice. The LD50 of GCTA was 4100 mg/kg with an oral single dose, vastly exceeding the therapeutic dose. Thus, GCTA exhibited antibacterial and anti-infective activity against S. Enteritidis. Our results provided insight into the molecular mechanisms of these antibacterial effects, and highlights the potential of GCTA as an alternative to antibiotics.

Antibacterial activities of Miang extracts against selected pathogens and the potential of the tannin-free extracts in the growth inhibition of Streptococcus mutans.

Bacterial pathogens have remained a major public health concern for several decades. This study investigated the antibacterial activities of Miang extracts (at non-neutral and neutral pH) against Bacillus cereus TISTR 747, Escherichia coli ATCC 22595, Salmonella enterica serovar Typhimurium TISTR 292 and Streptococcus mutans DMST 18777. The potential of Polyvinylpolypyrrolidone (PVPP)-precipitated tannin-free Miang extracts in growth-inhibition of the cariogenic Streptococcus mutans DMST 18777 and its biofilms was also evaluated. The tannin-rich fermented extracts had the best bacterial growth inhibition against S. mutans DMST 18777 with an MIC of 0.29 and 0.72 mg/mL for nonfilamentous fungi (NFP) Miang and filamentous-fungi-processed (FFP) Miang respectively. This observed anti-streptococcal activity still remained after PVPP-mediated precipitation of bioactive tannins especially, in NFP and FFP Miang. Characterization of the PVPP-treated extracts using High performance liquid chromatography quadrupole-time of flight-mass spectrometry (HPLC-QToF-MS) analysis, also offered an insight into probable compound classes responsible for the activities. In addition, Crystal violet-staining also showed better IC50 values for NFP Miang (4.30 ± 0.66 mg/mL) and FFP Miang (12.73 ± 0.11 mg/mL) against S. mutans DMST 18777 biofilms in vitro. Homology modeling and molecular docking analysis using HPLC-MS identified ligands in tannin-free Miang supernatants, was performed against modelled S. mutans DMST 18777 sortase A enzyme. The in silico analysis suggested that the inhibition by NFP and FFP Miang might be attributed to the presence of ellagic acid, flavonoid aglycones, and glycosides. Thus, these Miang extracts could be optimized and explored as natural active pharmaceutical ingredients (NAPIs) for applications in oral hygienic products.

Metal-phenolic network as precursor complex coating for forward osmosis membrane with enhanced antifouling property.

In this study, a multi-functional layer was developed based on the commercially available cellulose triacetate (CTA) forward osmosis (FO) membrane to improve its antifouling property. Tannic acid/ferric ion (TA/Fe3+) complexes were firstly coated as a precursor layer on the membrane surface via self-assembly. Afterwards, the tannic acid/diethylenetriamine (TA/DETA) hydrophilic functional layer was further coated, following Ag/polyvinylpyrrolidone (PVP) anti-bacterial layer was formed in situ through the reducibility of TA to obtain TA/Fe3+-TA/DETA-Ag/PVP-modified membrane. The optimized precursor layer was acquired by adjusting the buffer solution pH to 8, TA/Fe3+ ratio to 4 and the number of self-assembled layers to 5. The permeability testing results illustrated that the functional layer had an insignificant effect on the membrane transport parameters. The TA/Fe3+-TA/DETA-Ag/PVP-modified membrane simultaneously exhibited excellent physical and chemical stability. The coated membrane also demonstrated enhanced anti-bacterial properties, achieving 98.63 and 97.30% inhibition against Staphylococcus aureus and Escherichia coli, respectively. Furthermore, the dynamic fouling experiment showed a 12% higher water flux decrease for the TA/Fe3+-TA/DETA-Ag/PVP CTA membrane compared to the nascent CTA membrane, which proved its excellent antifouling performance. This work provides a feasible strategy to heighten the antifouling property of the CTA FO membrane.

Extracellular Vesicles from Ecklonia cava and Phlorotannin Promote Rejuvenation in Aged Skin.

Plant-derived extracellular vesicles (EVs) elicit diverse biological effects, including promoting skin health. EVs isolated from Ecklonia cava (EV-EC) carry heat shock protein 70 (HSP70), which inhibits key regulators such as TNF-α, MAPKs, and NF-κB, consequently downregulating matrix metalloproteinases (MMPs). Aging exacerbates oxidative stress, upregulating MAPK and NF-κB signaling and worsening extracellular matrix degradation in the skin. E. cava-derived phlorotannin (PT) mitigates MAPK and NF-κB signaling. We evaluated the impact of EV-EC and PT on skin rejuvenation using an in vitro keratinocyte senescence model and an in vivo aged-mouse model. Western blotting confirmed the presence of HSP70 in EV-EC. Treatment with EV-EC and PT in senescent keratinocytes increased HSP70 expression and decreased the expression of TNF-α, MAPK, NF-κB, activator protein-1 (AP-1), and MMPs. Oxidative stress was also reduced. Sequential treatment with PT and EV-EC (PT/EV-EC) yielded more significant results compared to individual treatments. The administration of PT/EV-EC to the back skin of aged mice mirrored the in vitro findings, resulting in increased collagen fiber accumulation and improved elasticity in the aged skin. Therefore, PT/EV-EC holds promise in promoting skin rejuvenation by increasing HSP70 expression, decreasing the expression of MMPs, and reducing oxidative stress in aged skin.

Extraction of tannin, colour and aroma compounds in pinot noir wines as affected by clone selection and whole bunch addition.

Our previous study revealed stem inclusion fermentation reduced anthocyanin, and increased tannin and aroma compounds responsible for green notes. This study further investigated the effect of clone selection and whole bunch fermentation on Pinot noir wine composition, with focus on tannin composition. Three treatments were conducted using two clones (AM10/5 and UCD5) in 2021 and 2022: 100% destemmed (DS), 30% whole bunch (WB30), and 60% whole bunch (WB60). WB60 increased stem and skin derived tannins but reduced seed derived tannin proportion in wines. Clone selection had an impact on tannin composition and an even greater impact on tannin concentration, colour, and aroma compounds. AM10/5 produced wines with higher tannin, polymeric pigments and darker colour. AM10/5 wines also had higher concentration of phenylethyl alcohol, but lower concentrations of 3-isobutyl-2-methoxypyrazine and ethyl esters, indicating more floral but less fruity and green notes.

Infection-Free and Enhanced Wound Healing Potential of Alginate Gels Incorporating Silver and Tannylated Calcium Peroxide Nanoparticles.

The treatment of chronic wounds involves precise requirements and complex challenges, as the healing process cannot go beyond the inflammatory phase, therefore increasing the healing time and implying a higher risk of opportunistic infection. Following a better understanding of the healing process, oxygen supply has been validated as a therapeutic approach to improve and speed up wound healing. Moreover, the local implications of antimicrobial agents (such as silver-based nano-compounds) significantly support the normal healing process, by combating bacterial contamination and colonization. In this study, silver (S) and tannylated calcium peroxide (CaO2@TA) nanoparticles were obtained by adapted microfluidic and precipitation synthesis methods, respectively. After complementary physicochemical evaluation, both types of nanoparticles were loaded in (Alg) alginate-based gels that were further evaluated as possible dressings for wound healing. The obtained composites showed a porous structure and uniform distribution of nanoparticles through the polymeric matrix (evidenced by spectrophotometric analysis and electron microscopy studies), together with a good swelling capacity. The as-proposed gel dressings exhibited a constant and suitable concentration of released oxygen, as shown for up to eight hours (UV-Vis investigation). The biofilm modulation data indicated a synergistic antimicrobial effect between silver and tannylated calcium peroxide nanoparticles, with a prominent inhibitory action against the Gram-positive bacterial biofilm after 48 h. Beneficial effects in the human keratinocytes cultured in contact with the obtained materials were demonstrated by the performed tests, such as MTT, LDH, and NO.

Polyphenolic Nanoparticle-Modified Probiotics for Microenvironment Remodeling and Targeted Therapy of Inflammatory Bowel Disease.

Inflammatory bowel diseases (IBDs) refer to multifaceted disorders in the intestinal microenvironment and microbiota homeostasis. In view of the broad bioactivity and high compatibility of polyphenols, there is considerable interest in developing a polyphenol-based collaborative platform to remodel the IBD microenvironment and regulate microbiota. Here, we demonstrated the coordination assembly of nanostructured polyphenols to modify probiotics and simultaneously deliver drugs for IBD treatment. Inspired by the distinctive structure of tannic acid (TA), we fabricated nanostructured pBDT-TA by using a self-polymerizable aromatic dithiol (BDT) and TA, which exhibited excellent antioxidant and anti-inflammatory capability in vitro. We thus coated pBDT-TA and sodium alginate (SA) to the surface of Escherichia coli Nissle 1917 layer by layer to construct the collaborative platform EcN@SA-pBDT-TA. The modified probiotics showed improved resistance to oxidative and inflammatory stress, which resulted in superior colon accumulation and retention in IBD model mice. Further, EcN@SA-pBDT-TA could alleviate dextran sulfate sodium (DSS)-induced colitis by controlling the inflammatory response, repairing intestinal barriers, and modulating gut microbiota. Importantly, EcN@SA-pBDT-TA-mediated IBD drug delivery could achieve an improved therapeutic effect in DSS model mice. Given the availability and functionality of polyphenol and prebiotics, we expected that nanostructured polyphenol-modified probiotics provided a solution to develop a collaborative platform for IBD treatment.

Identification and analysis of novel recessive alleles for Tan1 and Tan2 in sorghum.

Background: The identification and analysis of allelic variation are important bases for crop diversity research, trait domestication and molecular marker development. Grain tannin content is a very important quality trait in sorghum. Higher tannin levels in sorghum grains are usually required when breeding varieties resistant to bird damage or those used for brewing liquor. Non-tannin-producing or low-tannin-producing sorghum accessions are commonly used for food and forage. Tan1 and Tan2, two important cloned genes, regulate tannin biosynthesis in sorghum, and mutations in one or two genes will result in low or no tannin content in sorghum grains. Even if sorghum accessions contain dominant Tan1 and Tan2, the tannin contents are distributed from low to high, and there must be other new alleles of the known regulatory genes or new unknown genes contributing to tannin production. Methods: The two parents 8R306 and 8R191 did not have any known recessive alleles for Tan1 and Tan2, and it was speculated that they probably both had dominant Tan1 and Tan2 genotypes. However, the phenotypes of two parents were different; 8R306 had tannins and 8R191 had non-tannins in the grains, so these two parents were constructed as a RIL population. Bulked segregant analysis (BSA) was used to determine other new alleles of Tan1 and Tan2 or new Tannin locus. Tan1 and Tan2 full-length sequences and tannin contents were detected in wild sorghum resources, landraces and cultivars. Results: We identified two novel recessive tan1-d and tan1-e alleles and four recessive Tan2 alleles, named as tan2-d, tan2-e, tan2-f, and tan2-g. These recessive alleles led to loss of function of Tan1 and Tan2, and low or no tannin content in sorghum grains. The loss-of-function alleles of tan1-e and tan2-e were only found in Chinese landraces, and other alleles were found in landraces and cultivars grown all around the world. tan1-a and tan1-b were detected in foreign landraces, Chinese cultivars and foreign cultivars, but not in Chinese landraces. Conclusion: These results implied that Tan1 and Tan2 recessive alleles had different geographically distribution in the worldwide, but not all recessive alleles had been used in breeding. The discovery of these new alleles provided new germplasm resources for breeding sorghum cultivars for food and feed, and for developing molecular markers for low-tannin or non-tannin cultivar-assisted breeding in sorghum.

Investigating the efficacy of purified tannin extracts from underutilized temperate forages in reducing enteric methane emissions in vitro.

The study investigated how the concentration and composition of purified tannin extracts, at various inclusion rates, affect the ruminal in vitro fermentation parameters. Tannin extracts were isolated from four different forage species: birdsfoot trefoil (Lotus corniculatus), sulla (Hedysarum coronarium), big trefoil (Lotus pedunculatus), and salad burnet (Sanguisorba minor). Plants extracts were purified by Sephadex LH-20 gel chromatography and analyzed by UPLC-ESI-MS/MS. The results showed a large variation among the extracts from different species in terms of tannin composition and structural features. The extracts from salad burnet were dominated by hydrolysable tannins, comprising mainly ellagitannins. The extracts derived from sulla and big trefoil contained predominantly proanthocyanidins (PA), primarily composed of prodelphinidins with high mean degree of polymerisation (mDP). Birdsfoot trefoil extracts comprised procyanidin-rich PAs with low mDP. To determine whether the combined presence of tannins and flavonoid together lead to synergistic or antagonistic effects, the tannin extracts were incubated both with or without rutin at concentrations of 10, 20, and 30 g/kg DM, using a base substrate of perennial ryegrass (Lolium perenne, control). In general, all the tannin extracts decreased methane (CH4) production compared to the control, while no significant effect of rutin was observed on both gas (GP) and CH4 production, neither pure, nor in the simultaneous presence of tannins. The highest CH4 reduction (15%, at 30 g/kg DM) was observed from sulla and big trefoil extracts compared to control, but this was also supplemented with a concomitant reduction in GP (11%) indicating a reduction in feed digestibility. The extracts from birdsfoot trefoil and salad burnet reduced CH4 by up to 12% without significantly reducing GP, indicating the importance of tannin composition on ruminal fermentation.

Tannic acid inhibits Escherichia coli biofilm formation and underlying molecular mechanisms: Biofilm regulator CsgD.

Biofilms often engender persistent infections, heightened antibiotic resistance, and the recurrence of infections. Therefor, infections related to bacterial biofilms are often chronic and pose challenges in terms of treatment. The main transcription regulatory factor, CsgD, activates csgABC-encoded curli to participate in the composition of extracellular matrix, which is an important skeleton for biofilm development in enterobacteriaceae. In our previous study, a wide range of natural bioactive compounds that exhibit strong affinity to CsgD were screened and identified via molecular docking. Tannic acid (TA) was subsequently chosen, based on its potent biofilm inhibition effect as observed in crystal violet staining. Therefore, the aim of this study was to investigate the specific effects of TA on the biofilm formation of clinically isolated Escherichia coli (E. coli). Results demonstrated a significant inhibition of E. coli Ec032 biofilm formation by TA, while not substantially affecting the biofilm of the ΔcsgD strain. Moreover, deletion of the csgD gene led to a reduction in Ec032 biofilm formation, alongside diminished bacterial motility and curli synthesis inhibition. Transcriptomic analysis and RT-qPCR revealed that TA repressed genes associated with the csg operon and other biofilm-related genes. In conclusion, our results suggest that CsgD is one of the key targets for TA to inhibit E. coli biofilm formation. This work preliminarily elucidates the molecular mechanisms of TA inhibiting E. coli biofilm formation, which could provide a lead structure for the development of future antibiofilm drugs.

Improving the antinutritional profiles of common beans (Phaseolus vulgaris L.) moderately impacts carotenoid bioaccessibility but not mineral solubility.

Common beans are a common staple food with valuable nutritional qualities, but their high contents in antinutritional factors (ANFs) can decrease the bioavailability of (i) fat-soluble micronutrients including carotenoids and (ii) minerals. Our objective was to select ANF-poor bean lines that would not interfere with carotenoid and mineral bioavailability. To achieve this objective, seeds of commercial and experimental Phaseolus vulgaris L. bean lines were produced for 2 years and the bean's content in ANFs (saponins, phytates, tannins, total polyphenols) was assessed. We then measured carotenoid bioaccessibility and mineral solubility (i.e. the fraction of carotenoid and mineral that transfer into the aqueous phase of the digesta and is therefore absorbable) from prepared beans using in vitro digestion. All beans contained at least 200 mg/100 g of saponins and 2.44 mg/100 g tannins. The low phytic acid (lpa) lines, lpa1 and lpa12 exhibited lower phytate levels (≈ - 80%, p = 0.007 and p = 0.02) than their control BAT-93. However, this decrease had no significant impact on mineral solubility. HP5/1 (lpa + phaseolin and lectin PHA-E free) bean line, induced an improvement in carotenoid bioaccessibility (i.e., + 38%, p = 0.02, and + 32%, p = 0.005, for phytofluene bioaccessibility in 2021 and 2022, respectively). We conclude that decrease in the phytate bean content should thus likely be associated to decreases in other ANFs such as tannins or polyphenols to lead to significant improvement of micronutrient bioaccessibility.

Wearable dual-drug controlled release patch for psoriasis treatment.

Wearable drug delivery systems (DDS) have made significant advancements in the field of precision medicine, offering precise regulation of drug dosage, location, and timing. The performance qualities that wearable DDS has always strived for are simplicity, efficiency, and intelligence. This paper proposes a wearable dual-drug synergistic release patch. The patch is powered by a built-in magnesium battery and utilizes a hydrogel containing viologen-based hyperbranched polyamidoamine as both a cathode material and an integrated drug reservoir. This design allows for the simultaneous release of both dexamethasone and tannic acid, overcoming the limitations of monotherapy and ensuring effective synergy for on-demand therapy. In a mouse model with praziquimod-induced psoriasis, the patch demonstrated therapeutic efficacy at a low voltage. The inflammatory skin returned to normal after 5 days with the on-demand release of dual drugs. This work provides a promising treatment option considering its straightforward construction and the therapeutic advantages of dual-drug synergy.

A xanthan gum and carbomer-codispersed divalent manganese ion-loaded tannic acid nanoparticle adjuvanted inactivated pseudorabies virus vaccine induces balanced humoral and cellular immune responses.

Adjuvants including aluminum adjuvant (Alum) and oil-water emulsion have been widely used in inactivated pseudorabies virus (PRV) vaccines to improve their performance, however, they are not sufficient to protect from PRV infection because of the weak immune response and poor Th1-type immune response. Divalent manganese ion (Mn2+) has been reported to increase the cellular immune response significantly. In this work, a xanthan gum and carbomer-dispersed Mn2+-loaded tannic acid-polyethylene glycol (TPMnXC) nanoparticle colloid is developed and used as an adjuvant to improve the performance of the inactivated PRV vaccine. The good in vitro and in vivo biocompatibility of the developed TPMnXC colloid has been confirmed by the cell viability assay, erythrocyte hemolysis, blood routine analysis, and histological analysis of mouse organs and injection site. The TPMnXC-adjuvanted inactivated PRV vaccine (TPMnXC@PRV) significantly promotes higher and more balanced immune responses indicating with an increased specific total IgG antibody and IgG2a/IgG1 ratio, efficient splenocytes proliferation, and elevated Th1- and Th2-type cytokine secretion than those of control groups. Wild PRV challenge experiment is performed using mice as a model animal, achieving a protection rate of up to 86.67 %, which is much higher than those observed from the commercial Alum. This work not only demonstrates the high potentiality of TPMnXC in practical applications but also provides a new way to develop the Mn2+-loaded nanoadjuvant for veterinary vaccines.

Metal-polyphenol coordination nanosheets with synergistic peroxidase-like and photothermal properties for efficient antibacterial treatment.

Bacterial infections pose a serious threat to human health and socioeconomics worldwide. In the post-antibiotic era, the development of novel antimicrobial agents remains a challenge. Polyphenols are natural compounds with a variety of biological activities such as intrinsic antimicrobial activity and antioxidant properties. Metal-polyphenol obtained by chelation of polyphenol ligands with metal ions not only possesses efficient antimicrobial activity but also excellent biocompatibility, which has great potential for application in biomedical and food packaging fields. Herein, we developed metal-polyphenol coordination nanosheets named copper oxidized tannic acid quinone (CuTAQ) possessing efficient antibacterial and anti-biofilm effects, which was synthesized by a facile one-pot method. The synthesis was achieved by chelation of partially oxidized tannic acid (TA) with Cu2+ under mild conditions, which supports low-cost and large-scale production. It was demonstrated that CuTAQ exhibited high antibacterial activity via disrupting the integrity of bacterial cell membranes, inducing oxidative stress, and interfering with metabolism. In addition, CuTAQ exhibits excellent peroxidase catalytic activity and photothermal conversion properties, which play a significant role in enhancing its bactericidal and biofilm scavenging abilities. This study provides insights for rational design of innovative metal-polyphenol nanomaterials with efficient antimicrobial properties.

Design and Development of a Polymeric-Based Curcumin Nanoparticle for Drug Delivery Enhancement and Potential Incorporation into Nerve Conduits.

Peripheral nerve injuries (PNI) impact millions of individuals in the United States, prompting thousands of nerve repair procedures annually. Nerve conduits (NC) are commonly utilized to treat nerve injuries under 3 cm but larger gaps still pose a challenge for successful peripheral nerve regeneration (PNR) and functional recovery. This is partly attributed to the absence of bioactive agents such as stem cells or growth factors in FDA-approved conduits due to safety, harvesting, and reproducibility concerns. Therefore, curcumin, a bioactive phytochemical, has emerged as a promising alternative bioactive agent due to its ability to enhance PNR and overcome said challenges. However, its hydrophobicity and rapid degradation in aqueous solutions are considerable limitations. In this work, a nanoscale delivery platform with tannic acid (TA) and polyvinylpyrrolidone (PVP) was developed to encapsulate curcumin for increased colloidal and chemical stability. The curcumin nanoparticles (CurNPs) demonstrate significantly improved stability in water, reduced degradation rates, and controlled release kinetics when compared to free curcumin. Further, cell studies show that the CurNP is biocompatible when introduced to neuronal cells (SH-SY5Y), rat Schwann cells (RSC-S16), and murine macrophages (J774 A.1) at 5 µM, 5 µM, and 10 µM of curcumin, respectively. As a result of these improved physicochemical properties, confocal fluorescence microscopy revealed superior delivery of curcumin into these cells when in the form of CurNPs compared to its free form. A hydrogen peroxide-based oxidative stress study also demonstrated the CurNP's potential to protect J774 A.1 cells against excessive oxidative stress. Overall, this study provides evidence for the suitability of CurNPs to be used as a bioactive agent in NC applications.

Study on Quality Characteristic of Chebulae Fructus and Its Adulterants and Degradation Pathway of Hydrolyzable Tannins.

Chebulae Fructus (CF) is known as one of the richest sources of hydrolyzable tannins (HTs). In this study, ultra-performance liquid chromatography coupled with a photodiode array detector method was established for simultaneous determination of the 12 common phenolcarboxylic and tannic constituents (PTCs). Using this method, quantitative analysis was accomplished in CF and other four adulterants, including Terminaliae Belliricae Fructus, Phyllanthi Fructus, Chebulae Fructus Immaturus, and Canarii Fructus. Based on a quantitative analysis of the focused compounds, discrimination of CF and other four adulterants was successfully accomplished by hierarchical cluster analysis and principal component analysis. Additionally, the total contents of the 12 compounds that we focused on in this study were unveiled as 148.86 mg/g, 96.14 mg/g, and 18.64 mg/g in exocarp, mesocarp, and endocarp and seed of CF, respectively, and PTCs were witnessed to be the most abundant in the exocarp of CF. Noticeably, the HTs (chebulagic acid, chebulanin acid, chebulinic acid, and punicalagin) were observed to be ultimately degraded to chebulic acid, gallic acid, and ellagic acid during sunlight-drying of the fresh fruits. As a result, our study indicated that CF and its adulterants could be distinguished by the observed 12 PTCs, which were mainly distributed in the exocarp of the fruits. The HTs were prone to degrade into the three simple phenolcarboxylic acids during drying or processing, allowing us to obtain a more comprehensive understanding of the PTCs, with great significance in the improved quality of CF and related products.

Dendritic Cell Immune Modulation via Polyphenol Membrane Coatings.

Cellular hitchhiking is an emerging strategy for the in vivo control of adoptively transferred immune cells. Hitchhiking approaches are primarily mediated by adhesion of nano and microparticles to the cell membrane, which conveys an ability to modulate transferred cells via local drug delivery. Although T cell therapies employing this strategy have progressed into the clinic, phagocytic cells including dendritic cells (DCs) are much more challenging to engineer. DC vaccines hold great potential for a spectrum of diseases, and the combination drug delivery is an attractive strategy to manipulate their function and overcome in vivo plasticity. However, DCs are not compatible with current hitchhiking approaches due to their broad phagocytic capacity. In this work, we developed and validated META (membrane engineering using tannic acid) to enable DC cellular hitchhiking for the first time. META employs the polyphenol tannic acid (TA) to facilitate supramolecular assembly of protein drug cargoes on the cell membrane, enabling the creation of cell surface-bound formulations for local drug delivery to carrier DCs. We optimized META formulations to incorporate and release protein cargoes with varying physical properties alone and in combination and to preserve DC viability and critical functions such as migration. We further show that META loaded with either a pro- or anti-inflammatory cargo can influence the carrier cell phenotype, thus demonstrating the flexibility of the approach for applications from cancer to autoimmune disease. Overall, this approach illustrates a new platform for the local control of phagocytic immune cells as a next step to advance DC therapies in the clinic.