The Related Mechanisms Predicted through Network-Based Pharmacological Analysis and the Anti-Inflammatory Effects of Fraxinus rhynchophylla Hance Bark on Contact Dermatitis in Mice.

Fraxinus rhynchophylla Hance bark has been used to treat patients with inflammatory or purulent skin diseases in China, Japan, and Korea. This study was undertaken to determine the mechanism responsible for the effects of F. rhynchophylla and whether it has a therapeutic effect in mice with contact dermatitis (CD). In this study, the active compounds in F. rhynchophylla, their targets, and target gene information for inflammatory dermatosis were investigated using network-based pharmacological analysis. Docking analysis was conducted using AutoDock Vina. In addition, the therapeutic effect of an ethanolic extract of F. rhynchophylla (EEFR) on skin lesions and its inhibitory effects on histopathological abnormalities, inflammatory cytokines, and chemokines were evaluated. Finally, its inhibitory effects on the nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) signalling pathways were observed in RAW 264.7 cells. In our results, seven active compounds were identified in F. rhynchophylla, and six were associated with seven genes associated with inflammatory dermatosis and exhibited a strong binding affinity (<-6 kcal/mol) to prostaglandin G/H synthase 2 (PTGS2). In a murine 1-fluoro-2,4-dinitrobenzene (DNFB) model, topical EEFR ameliorated the surface symptoms of CD and histopathological abnormalities. EEFR also reduced the levels of tumour necrosis factor (TNF)-α, interferon (IFN)-γ, interleukin (IL)-6, and monocyte chemotactic protein (MCP)-1 in inflamed tissues and inhibited PTGS2, the nuclear translocation of NF-κB (p65), and the activation of c-Jun N-terminal kinases (JNK) in RAW 264.7 cells. In conclusion, the bark of F. rhynchophylla has potential use as a therapeutic or cosmetic agent, and the mechanism responsible for its effects involves the suppression of inflammatory mediators, nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor (IκB)-α degradation, the nuclear translocation of NF-κB, and JNK phosphorylation.

Reactive Polymer Targeting dsRNA as Universal Virus Detection Platform with Enhanced Sensitivity.

Reactive poly(pentafluorophenyl acrylate) (PPFPA)-grafted surfaces offer a versatile platform to immobilize biomolecules. Here, we utilize PPFPA-grafted surface and double-stranded RNA (dsRNA) recognizing J2 antibody to construct a universal virus detection platform with enhanced sensitivity. PPFPA on silicon substrates is prepared, and surface hydrophilicity is modulated by partial substitution of the pentafluorophenyl units with poly(ethylene glycol). Following dsRNA antibody immobilization, the prepared surfaces can distinguish long dsRNAs from single-stranded RNAs of the same length and short dsRNAs. As long dsRNAs are common byproducts of viral transcription/replication, these surfaces can detect the presence of different kinds of viruses without prior knowledge of their genomic sequences. To increase dsRNA detection sensitivity, a two-step method is devised where the captured dsRNAs are visualized with multiple fluorophore-tagged J2 antibodies. We show that the developed platform can differentiate foreign long dsRNAs from cellular dsRNAs and other biomolecules present in the cell lysate. Moreover, when tested against cells infected with hepatitis A or C viruses, both viruses are successfully detected using a single platform. Our study shows that the developed PPFPA platform immobilized with J2 antibody can serve as a primary diagnostic tool to determine the infection status for a wide range of viruses.

The gut microbe pair of Oribacterium sp. GMB0313 and Ruminococcus sp. GMB0270 confers complete protection against SARS-CoV-2 infection by activating CD8+ T cell-mediated immunity.

Despite the potential protective role of the gut microbiome against COVID-19, specific microbes conferring resistance to COVID-19 have not yet been identified. In this work, we aimed to identify and validate gut microbes at the species level that provide protection against SARS-CoV-2 infection. To identify gut microbes conferring protection against COVID-19, we conducted a fecal microbiota transplantation (FMT) from an individual with no history of COVID-19 infection or immunization into a lethal COVID-19 hamster model. FMT from this COVID-19-resistant donor resulted in significant phenotypic changes related to COVID-19 sensitivity in the hamsters. Metagenomic analysis revealed distinct differences in the gut microbiome composition among the hamster groups, leading to the identification of two previously unknown bacterial species: Oribacterium sp. GMB0313 and Ruminococcus sp. GMB0270, both associated with COVID-19 resistance. Subsequently, we conducted a proof-of-concept confirmation animal experiment adhering to Koch's postulates. Oral administration of this gut microbe pair, Oribacterium sp. GMB0313 and Ruminococcus sp. GMB0270, to the hamsters provided complete protection against SARS-CoV-2 infection through the activation of CD8+ T cell mediated immunity. The prophylactic efficacy of the gut microbe pair against SARS-CoV-2 infection was comparable to, or even superior to, current mRNA vaccines. This strong prophylactic efficacy suggests that the gut microbe pair could be developed as a host-directed universal vaccine for all betacoronaviruses, including potential future emerging viruses.

Oral delivery of a host-directed antiviral, niclosamide, as a cholate-coated nanoformulation.

Potentially significant drug candidates often face elimination from consideration due to the lack of an effective method for systemic delivery. The poor solubility of these candidates has posed a major obstacle for their development as oral pills or injectables. Niclosamide, a host-directed antiviral, is a good example. In this study, a nanoformulation technology that allows for the non-covalent formulation of niclosamide with cholic acids was developed. This formulation enables efficient systemic delivery through endocytosis and enterohepatic circulation of bile-acid-coated nanoparticles. The oral bioavailability of niclosamide-delivery nanoparticles (NDNs) was significantly enhanced to 38.3%, representing an eight-fold increase compared with pure niclosamide. Consequently, the plasma concentration of niclosamide for the NDN formulation reached 1179.6 ng/mL, which is 11 times higher than the therapeutic plasma level. This substantial increase in plasma level contributed to the complete resolution of clinical symptoms in animals infected with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). This nanoformulation not only provides an orally deliverable antiviral drug for SARS-CoV-2 with improved pharmaceutical bioavailability, but also offers a solution to the systemic delivery challenges faced by potentially significant drug candidates.

Nectandrin B significantly increases the lifespan of Drosophila - Nectandrin B for longevity.

Phytochemicals are increasingly recognized in the field of healthy aging as potential therapeutics against various aging-related diseases. Nutmeg, derived from the Myristica fragrans tree, is an example. Nutmeg has been extensively studied and proven to possess antioxidant properties that protect against aging and alleviate serious diseases such as cancer, heart disease, and liver disease. However, the specific active ingredient in nutmeg responsible for these health benefits has not been identified thus far. In this study, we present evidence that Nectandrin B (NecB), a bioactive lignan compound isolated from nutmeg, significantly extended the lifespan of the fruit fly Drosophila melanogaster by as much as 42.6% compared to the control group. NecB also improved age-related symptoms including locomotive deterioration, body weight gain, eye degeneration, and neurodegeneration in aging D. melanogaster. This result represents the most substantial improvement in lifespan observed in animal experiments to date, suggesting that NecB may hold promise as a potential therapeutic agent for promoting longevity and addressing age-related degeneration.

Anti-inflammatory Effects of Ampelopsis Japonica Root on Contact Dermatitis in Mice.

OBJECTIVE: To investigate the anti-inflammatory potential of Ampelopsis japonica on contact dermatitis (CD). METHODS: A total of 38 Balb/c mice were divided into 5 groups by using a random number table: normal mice (n=6), CD model mice (n=8), CD mice treated with 3 or 30 mg/kg of the ethanol extract of A. japonica (EEAJ, n=8) and 7.5 mg/kg dexamethasone treated CD mice (DEX, n=8). CD was induced using topical application of 1-fluoro-2,4-dinitrofluorobenzene in mice. EEAJ and DEX were topically applied to the shaved skin of each mouse for 6 days, and the effects of EEAJ and DEX on skin lesions and color, histopathological abnormalities such as epidermal hyperplasia and immune cell infiltration, and tumor necrosis factor (TNF)-α, interleukin-6 (IL-6), and monocyte chemoattractant protein-1 (MCP-1) production were investigated. The effects on changes in body weights and spleen/body weight ratio were also investigated. RESULTS: EEAJ at 30 mg/kg significantly prevented scaling, erythema and enlargement of skin weight compared to using carbon dioxide. EEAJ also prevented epithelial hyperplasia and immune cell infiltrations induced by repeated application of DNFB (P<0.01). In addition, EEAJ significantly lowered levels of TNF-α, IL-6 and MCP-1 (P<0.05 or P<0.01). The anti-inflammatory effects of EEAJ were similar to those of DEX. CONCLUSION: A. japonica may be a new therapeutic agent with the potential to reduce or replace corticosteroids and its mechanisms are closely related to regulation of TNF-α production.

Gentiana scabra Bunge roots alleviates skin lesions of contact dermatitis in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: The roots and rhizomes of Gentiana scabra Bunge in the family Gentianaceae comprise a major herbal medicine for skin diseases caused by wind-heat or dampness-heat in China, Japan and Korea. This treatment can clear away heat and dry dampness and purge fire from the liver and gallbladder. AIM OF THE STUDY: This study was designed to investigate the therapeutic potential and anti-inflammatory effects of G. scabra, roots and rhizomes. MATERIALS AND METHODS: Thin layer chromatography (TLC) and high performance liquid chromatography (HPLC) revealed the presence of gentiopicrin in the roots and rhizomes of G. scabra. We then investigated the effects of ethanol extract of G. scabra, roots and rhizomes (EEGS) on skin lesions and thickness, erythema and melanin index, histopathological abnormalities, and cytokine and chemokine production in mice with contact dermatitis (CD) induced by 1-fluoro-2,4-dinitrofluorobenzene (DNFB). Moreover, the effects of EEGS on body weights and spleen body weight ratio were evaluated. RESULTS: Topical application of EEGS alleviated skin lesions such as surface roughness, excoriations and scabs on the skin of CD mice, as well as prevented skin enlargement, and lowered the erythema and melanin index. In addition, EEGS prevented hyperkeratosis, epidermal hyperplasia and immune cell infiltration, and inhibited TNF-α, IFN-γ, IL-6 and MCP-1 production in inflamed tissues. EEGS did not affect changes in body weights and spleen body weight ratio in contrast to dexamethasone. CONCLUSIONS: These data indicate that the roots and rhizomes of G. scabra can be used as anti-inflammatory agents for CD with relative safety and that its therapeutic mechanisms are related to regulation of pro-inflammatory cytokines such as TNF-α and IFN-γ.

Preparation of Poly(pentafluorophenyl acrylate) Functionalized SiO2 Beads for Protein Purification.

We demonstrate a simple method to prepare poly(pentafluorophenyl acrylate) (poly(PFPA)) grafted silica beads for antibody immobilization and subsequent immunoprecipitation (IP) application. The poly(PFPA) grafted surface is prepared via a simple two-step process. In the first step, 3-aminopropyltriethoxysilane (APTES) is deposited as a linker molecule onto the silica surface. In the second step, poly(PFPA) homopolymer, synthesized via the reversible addition and fragmentation chain transfer (RAFT) polymerization, is grafted to the linker molecule through the exchange reaction between the pentafluorophenyl (PFP) units on the polymer and the amine groups on APTES. The deposition of APTES and poly(PFPA) on the silica particles are confirmed by X-ray photoelectron spectroscopy (XPS), as well as monitored by the particle size change measured via dynamic light scattering (DLS). To improve the surface hydrophilicity of the beads, partial substitution of poly(PFPA) with amine-functionalized poly(ethylene glycol) (amino-PEG) is also performed. The PEG-substituted poly(PFPA) grafted silica beads are then immobilized with antibodies for IP application. For demonstration, an antibody against protein kinase RNA-activated (PKR) is employed, and IP efficiency is determined by Western blotting. The analysis results show that the antibody immobilized beads can indeed be used to enrich PKR while non-specific protein interactions are minimal.

Decoction of Dictamnus Dasycarpus Turcz. Root Bark Ameliorates Skin Lesions and Inhibits Inflammatory Reactions in Mice with Contact Dermatitis.

BACKGROUND: The root bark of Dictamnus dasycarpus Turcz. (Dictamni Radicis Cortex) has been widely used to treat skin diseases in Korea, and its anti-inflammatory efficacies were recently reported. OBJECTIVE: The paper aims to investigate the inhibitory effects of decoction of Dictamni Radicis Cortex (DDRC) in mice with contact dermatitis (CD). MATERIALS AND METHODS: We investigated the effects of DDRC on skin lesion characteristics such as crust, scales, incrustation and petechiae, the erythema and melanin indexes, skin thickness, histopathologic changes, and cytokine production in 1-fluoro-2,4-dinitrofluorobenzene (DNFB)-induced CD mice. RESULTS: Topical application of DDRC ameliorated crust, scales, incrustation, and induced by DNFB. In addition, DDRC lowered the erythema index significantly (P < 0.05). DDRC effectively inhibited enlargement of skin thickness (P < 0.05). Histopathologic observation showed that DDRC inhibited epidermal hyperplasia, hyperkeratosis, and spongiotic changes. Finally, DDRC decreased production levels of IFN-γ, TNF-α and IL-6 induced by repeated application of DNFB (P < 0.05). CONCLUSION: These data suggest that DDRC can be used in the treatment of inflammatory skin diseases including CD. Moreover, these results are closely related to the decreasing production of TNF-α IFN-γ and IL-6 in inflamed tissues. SUMMARY: DDRC ameliorated skin lesions such as crust, scales, incrustation and petechiae, and lowered erythema index on skin surface in CD miceDDRC inhibited enlargement of dorsal skin and prevented epidermal hyperplasia, hyperkeratosis, and spongiotic changes in inflamed tissuesDDRC reduced the levels of TNF-α, IFN-γ, and IL-6 in inflamed tissues of CD miceDDRC did not affect spleen/body weight ratio in CD mice. Abbreviations used: DDRC: decoction of Dictamni Radicis Cortex, CD: contact dermatitis, DNFB: 1-fluoro-2,4-dinitrofluorobenzene, AOO: acetone and olive oil, DEX: dexamethasone, CBA: cytometric bead array.

Fixed-volume metering microdispenser module.

In this work, we present a novel fixed-volume metering microdispenser module using the sPROMs (structurally programmable microfluidic systems) technology. We have designed, simulated, fabricated and characterized an array of microdispensers with volumes ranging from 50 nL [nanoliter] to 150 nL. We have characterized several key components of the microdispenser, such as passive microvalves and the air-driven liquid column splitting process, using extensive simulations. The fabricated devices show extremely good accuracy (99.2%) and repeatability characteristics. We also present a simple technique for unloading the sub-microL [microliter] volumes from the microfluidic chip for measurement purposes. The dispensers realized in this work have immediate applications as a key ingredient of the lab-on-a-chip device.