A dendritic cell-recruiting, antimicrobial blood clot hydrogel for melanoma recurrence prevention and infected wound management.

Surgical resection, the mainstay for melanoma treatment, faces challenges due to high tumor recurrence rates and complex postoperative wound healing. Chronic inflammation from residual disease and the risk of secondary infections impede healing. We introduce an innovative, injectable hydrogel system that integrates a multifaceted therapeutic approach. The hydrogel, crosslinked by calcium ions with sodium alginate, encapsulates a blood clot rich in dendritic cells (DCs) chemoattractants and melanoma cell-derived nanovesicles (NVs), functioning as a potent immunostimulant. This in situ recruitment strategy overcomes the limitations of subcutaneous tumor vaccine injections and more effectively achieves antitumor immunity. Additionally, the hydrogel incorporates Chlorella extracts, enhancing its antimicrobial properties to prevent wound infections and promote healing. One of the key findings of our research is the dual functionality of Chlorella extracts; they not only expedite the healing process of infected wounds but also increase the hydrogel's ability to stimulate an antitumor immune response. Given the patient-specific nature of the blood clot and NVs, our hydrogel system offers customizable solutions for individual postoperative requirements. This personalized approach is highlighted by our study, which demonstrates the synergistic impact of the composite hydrogel on preventing melanoma recurrence and hastening wound healing, potentially transforming postsurgical melanoma management.

Antiviral activity of Morus alba L. extract against pseudorabies virus.

ETHNOPHARMACOLOGICAL RELEVANCE: Morus alba L. are widely used as ethnomedicine and functional food in China, Japan, Korea and other Asian countries. Morus alba L. have a variety of pharmacological activity such as antiviral, antioxidation, anti-cholesterol, anticancer, hypoglycemia, and neuroprotection. Morus alba L. has demonstrated antiviral efficacy against influenza viruses, SARS-CoV-2 and so on, but its potential activity against pseudorabies virus (PRV) remains uncertain. AIM OF THE STUDY: This study endeavors to delve into the anti-pseudorabies virus (PRV) potential of the ethanol extract of Morus alba L. leaves (MLE), while simultaneously elucidating its underlying mechanism of action. MATERIALS AND METHODS: The anti-PRV activities of Morus alba L. extracts at different concentrations were evaluated by qPCR and immunoblotting. The inhibitory effects of MLE on PRV replication in three distinct treatment modes (pretreatment, co-treatment, and post-treatment) were detected by qPCR and indirect immunofluorescence assays. qPCR was used to investigate the effects of MLE on PRV attachment, entrance, and cytokine expression in PRV-infected cells. The chemical components in MLE were analyzed by UPLC-MS/MS. RESULTS: MLE significantly inhibits PRV replication and protein expression in a dose-dependent manner. MLE displays inhibitory effects against PRV at three different modes of treatment. The most significant inhibitory effect of MLE was observed when used in co-treatment mode, resulting in an inhibition rate of 99.42%. MLE inhibits PRV infection in the early stage. MLE inhibits PRV infection by affecting viral attachment and viral entry. Furthermore, MLE exerts its inhibition on PRV replication by mitigating the heightened expression of cytokines (TNF-α and IFN-α) triggered by PRV. Analysis of its chemical composition highlights phenolic acids and flavonoids as the principal constituents of MLE. CONCLUSION: The results illustrate that MLE effectively impedes PRV infection by suppressing viral adsorption and entry, while also curbing the expression of antiviral cytokines. Therefore, MLE may be a potential resource for creating new medications to treat human and animal PRV infections.

Sea buckthorn extract mitigates chronic obstructive pulmonary disease by suppression of ferroptosis via scavenging ROS and blocking p53/MAPK pathways.

ETHNOPHARMACOLOGICAL RELEVANCE: Sea buckthorn (Hippophae rhamnoides), a traditional Tibetan medicinal herb, exhibits protective effects against cardiovascular and respiratory diseases. Although Sea buckthorn extract (SBE) has been confirmed to alleviate airway inflammation in mice, its therapeutic effect and underlying mechanism on chronic obstructive pulmonary disease (COPD) requires further clarification. AIM OF THE STUDY: To elucidate the alleviative effect and molecular mechanism of SBE on lipopolysaccharides (LPS)/porcine pancreatic elastase (PPE)-induced COPD by blocking ferroptosis. METHODS: The anti-ferroptotic effects of SBE were evaluated in human BEAS-2B bronchial epithelial cells using CCK8, RT-qPCR, western blotting, and transmission electron microscopy. Transwell was employed to detect chemotaxis of neutrophils. COPD model was induced by intranasally administration of LPS/PPE in mice and measured by alterations of histopathology, inflammation, and ferroptosis. RNA-sequencing, western blotting, antioxidant examination, flow cytometry, DARTS, CETSA, and molecular docking were then used to investigate its anti-ferroptotic mechanisms. RESULTS: In vitro, SBE not only suppressed erastin- or RSL3-induced ferroptosis by suppressing lipid peroxides (LPOs) production and glutathione (GSH) depletion, but also suppressed ferroptosis-induced chemotactic migration of neutrophils via reducing mRNA expression of chemokines. In vivo, SBE ameliorated LPS/PPE-induced COPD phenotypes, and inhibited the generation of LPOs, cytokines, and chemokines. RNA-sequencing showed that p53 pathway and mitogen-activated protein kinases (MAPK) pathway were implicated in SBE-mediated anti-ferroptotic action. SBE repressed erastin- or LPS/PPE-induced overactivation of p53 and MAPK pathway, thereby decreasing expression of diamine acetyltransferase 1 (SAT1) and arachidonate 15-lipoxygenase (ALOX15), and increasing expression of glutathione peroxidase 4 (GPX4) and solute carrier family 7 member 11 (SLC7A11). Mechanistically, erastin-induced elevation of reactive oxygen species (ROS) was reduced by SBE through directly scavenging free radicals, thereby contributing to its inhibition of p53 and MAPK pathways. CETSA, DARTS, and molecular docking further showed that ROS-generating enzyme nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 4 (NOX4) may be the target of SBE. Overexpression of NOX4 partially impaired the anti-ferroptotic activity of SBE. CONCLUSION: Our results demonstrated that SBE mitigated COPD by suppressing p53 and MAPK pro-ferroptosis pathways via directly scavenging ROS and blocking NOX4. These findings also supported the clinical application of Sea buckthorn in COPD therapy.

In vitro anti-inflammatory, anticancer effects and phytochemical characterisation of organic extracts from Aristolochia olivieri Colleg. ex Boiss.

Natural extract plays a crucial role in our lives, major compound in the n-hexane (AR-H) and the ethyl acetate (AR-E) Aristolochia olivieri extracts was n-hexadecanoic acid, and of the methanol extract (AR-M) was pentacosane. The AR-M extract had a strong ability to induce mRNA expression of an inflammatory cytokine, IL-6, as an M1-like macrophage subset compared to the negative control (DMSO-treated cells). In contrast, AR-E treatment showed strong anti-inflammatory activity against macrophages. The AR-H extract had a moderate inflammatory effect against macrophages. The IC50 results of the anticancer assays ranged from 58.29 to 451.03 µg/mL for the three extracts. The anticancer action of the AR-E extract against U-87MG cells was higher (58.29 µg/mL) than that of AR-H and AR-M (156.38 and 196.14 µg/mL, respectively). The greater cytotoxicity effect observed with the AR-E extract against U-87MG can be linked to its high content of hexadecanoic acid (32.49%) and linolenic acid (12.90%).

Phenolic Glycoside Monomer from Reed Rhizome Inhibits Melanin Production via PI3K-Akt and Ras-Raf-MEK-ERK Pathways.

INTRODUCTION: Melanogenesis, the process responsible for melanin production, is a critical determinant of skin pigmentation. Dysregulation of this process can lead to hyperpigmentation disorders. METHOD: In this study, we identified a novel Reed Rhizome extract, (1'S, 2'S)-syringyl glycerol 3'-O-ß-D-glucopyranoside (compound 5), and evaluated its anti-melanogenic potential in zebrafish models and in vitro assays. Compound 5 inhibited melanin synthesis by 36.66% ± 14.00% and tyrosinase in vivo by 48.26% ± 6.94%, surpassing the inhibitory effects of arbutin. Network pharmacological analysis revealed key targets, including HSP90AA1, HRAS, and PIK3R1, potentially involved in the anti-melanogenic effects of compound 5. RESULTS: Molecular docking studies supported the interactions between compound 5 and these targets. Further, gene expression analysis in zebrafish indicated that compound 5 up-regulates hsp90aa1.1, hrasa, and pik3r1, and subsequently down-regulating mitfa, tyr, and tyrp1, critical genes in melanogenesis. CONCLUSION: These findings suggest that compound 5 inhibits melanin production via PI3K-Akt and Ras-Raf-MEK-ERK signaling pathways, positioning it as a promising candidate for the treatment of hyperpigmentation.

Synthesis of Luminescent Copper Nanoparticles Using Couroupita guianensis Flower Extract: Evaluation of Antibacterial and Anticancer Activities.

The biosynthesis of nanoparticles is a crucial research area aimed at developing innovative, cost-effective, and eco-friendly synthesis techniques for various applications. Herein, we synthesized copper oxide nanoparticles (CuNPs) using Couroupita guianensis flower extract via a simple green synthesis method. These green CuNPs demonstrate promising antimicrobial activity and anticancer activity against A549 nonsmall cell lung cancer (NSCLC) cells. We comprehensively characterized the CuNPs using UV spectrum, XRD, FTIR, SEM, and EDS analyses. The antibacterial and anticancerous performance is attributed to their spherical-like morphology, which enhances effective interaction with bacterial and cancer cells. Moreover, CuNPs proved effective in inactivating Escherichia coli, achieving 2%, 52%, and 99% inactivation at 0, 30, and 60 min, respectively, and Listeria monocytogenes, achieving 1%, 48%, and 98% inactivation at 0, 30, and 60 min, respectively, under visible light. Furthermore, the CuNPs exhibited significant anticancer activity against A549 NSCLC cells, achieving cell viability reductions of 10%, 30%, 50%, 70%, 83%, and 91% at concentrations of 25, 50, 100, 150, 200, and 250 µg/mL, respectively. The green synthesized CuNPs demonstrate their potential in biomedical applications.

Design of Bionanomaterial of Chitosan Carbohydrate Polymer Composited with Broccoli Extract and Zinc Oxide Nanoparticles: Anticancer Activity in Human Osteosarcoma.

In the current research, a chitosan/broccoli extract/ZnO nanoparticle (CH/BE/ZnO) bionanocomposite was created. The physicochemical properties of CH/BE/ZnO bionanocomposite were investigated using a variety of methods, including field emission scanning electron microscopy (FESEM), elemental analysis (CHN-O), X-ray diffraction (XRD), Fourier transform infrared spectrum (FTIR), Brunauer-Emmett-Teller (BET), and transmission electron microscopy (TEM). The CH/BE/ZnO bionanocomposite's biological activity was assessed by examining its cytotoxicity capabilities against a bone cancer cell line (MG63). The total pore volume and specific surface area of CH/BE/ZnO are 0.134 cm3/g and 16.99 m2/g, respectively. The IC50 results for CH/BE/ZnO bionanocomposite in bone cancer investigations using the MTT test against the MG63 cell line was 115 µg/mL. The results indicate that the CH/BE/ZnO bionanocomposite is an effective chemotherapeutic agent against human osteosarcoma. The CH/BE/ZnO bionanocomposite showed high performance and structure, which means innovating nanomaterial agents for biological applications in the future.

Antibiofilm activity of Morganella morganii JB8F and Pseudomonas fluorescens JB3B compound to control single and multi-species of aquaculture pathogens.

BACKGROUND: Indonesia is a country that uses half or more aquatic foods as protein intake. The increased production in aquaculture industries might cause several problems, such as bacterial disease resulting in mass mortality and economic losses. Antibiotics are no longer effective because aquaculture pathogens can form biofilm. Biofilm is a microbial community that aggregates and firmly attaches to living or non-living surfaces. Biofilm formation can be caused by environmental stress, the presence of antibiotics, and limited nutrients. Therefore, it is important to explore antibiofilm to inhibit biofilm formation and/or eradicate mature biofilm. Phyllosphere bacteria can produce bioactive compounds for antimicrobial, antibiofilm, and anti-quorum sensing. Three aquaculture pathogens were used in this study, such as Aeromonas hydrophila, Streptococcus agalactiae, and Vibrio harveyi. RESULTS: Pseudomonas fluorescens JB3B and Morganella morganii JB8F extracts could disrupt single and multi-species biofilms. Both extracts could inhibit single biofilm formation from one to seven days of incubation time. We confirmed the destruction activity on multi-species biofilm using light microscope and scanning electron microscope. Using GC-MS analysis, indole was the most active fraction of the P. fluorescens JB3B extracts and octacosane from the M. morganii JB8F extract. We also conducted a toxicity test using brine shrimp lethality assay on P. fluorescens JB3B and M. morganii JB8F extracts. P. fluorescens JB3B, M. morganii JB8F, and a mixture of both extracts were confirmed non-toxic according to the LC50 value of the brine shrimp lethality test. CONCLUSIONS: P. fluorescens JB3B and M. morganii JB8F phyllosphere extracts had antibiofilm activity to inhibit single biofilm and disrupt single and multi-species biofilm of aquaculture pathogens. Both extracts could inhibit single species biofilm until seven days of incubation. Bioactive compounds that might contribute to antibiofilm properties were found in both extracts, such as indole and phenol. P. fluorescens JB3B, M. morganii JB8F extracts, and mixture of both extracts were non-toxic against Artemia salina.

The impact of Codonopsis Pilosulae and Astragalus Membranaceus extract on growth performance, immunity function, antioxidant capacity and intestinal development of weaned piglets.

Introduction: The objective of this study was to examine the impact of Codonopsis pilosula and Astragalus membranaceus extract (CA) on the growth performance, diarrhea rate, immune function, antioxidant capacity, gut microbiota, and short-chain fatty acids (SCFAs) in weaned piglets. Methods: A total of forty-eight 31-day-old weaned piglets, were divided into four groups randomly based on the treatment type: control group (CON), low dose group (LCA, 0.5% CA), medium dose group (MCA, 1.0% CA), and high dose group (HCA, 1.5% CA), and were fed for a duration of 28 days. On the morning of the 1st and 29th day, the piglets were assessed by weighing them on an empty stomach, recording their daily feed intake and diarrhea rate. Results: CA increased the average daily weight gain and reduced F/G without significant differences, and the diarrhea rate was reduced in the LCA and MCA groups. Furthermore, the levels of T-AOC, SOD, GSH-Px, and MDA were increased. The levels of T-AOC in the LCA group and the MCA group, SOD in the MCA group, and GSH-Px in the HCA group were significantly higher compared with the CON group (p < 0.05). Additionally, CA significantly increased IgM, IgG, and IgA levels (p < 0.05). The results of gut microbiota analysis showed that the bacterial population and diversity of faeces were changed with the addition of CA to basal diets. CA increased the abundance of the beneficial bacterial Firmicutes and Lactobacillus. Additionally, Compared with the CON group, CA significantly increased the SCFAs content of weaned piglets (p < 0.05). Discussion: CA can alleviate oxidative stress, improve immunity and antioxidant capacity, increase the abundance of beneficial bacteria, and the content of SCFAs for improving the intestinal barrier of piglets, thus promoting growth and reducing diarrhea rate in weaned piglets.

Green Synthesis of New Derivatives of Iminothiazole Using Cefixime and Removing Organic Pollutants from Aqueous Environment by Employing Cu@KF/Clinoptilolite NPs.

AIMS AND OBJECTIVE: In this research, multicomponent reactions of cefixime, isothiocyanates, and alkyl bromides were carried out for the synthesis of new iminothiazole derivatives with high yields in water as the solvent at room temperature in the presence of catalytic amounts of Cu@KF/CP NPs as catalysts. Also, the ability of Cu@KF/Clinoptilolite nanoparticles (NPs) to adsorb and remove 4-NP and cefixime from water was investigated. The Cu@KF/Clinoptilolite nanoparticles were synthesized by employing a water extract of Petasites hybridus rhizomes. MATERIALS AND METHODS: For this experiment, all of the components obtained from Fluka and Merck were subjected to further purification. The antibiotic used in this investigation, cefixime, was obtained from a pharmaceutical facility situated in Sari, Mazandaran, Iran. The antibiotic factory is located in Sari City, Iran. All solutions were prepared using distilled water. The shape of Cu@KF/CP nanoparticles was analyzed using images obtained from a Holland Philips XL30 scanning electron microscope. An analysis was performed on the crystalline structure of Cu@KF/CP nanoparticles (NPs), and a room temperature X-ray diffraction (XRD) examination was carried out utilizing a Holland Philips Xpert X-ray powder diffractometer. The X-ray diffraction (XRD) examination was conducted using CuK radiation, which has a wavelength of 0.15406 nm. The analysis covered a 2ε angle range from 20 to 80°. The nanostructures that were produced were chemically analyzed using X-ray energy dispersive spectroscopy (EDS) with an S3700N equipment. The morphology and dimensions of Cu@KF/CP nanoparticles were characterized using a Philips EM208 transmission electron microscope operated at an acceleration voltage of 90 kV. RESULTS: The primary objective of this study was to develop a sustainable approach for producing new iminothiazole derivatives 4. This was achieved using a highly efficient three-component reaction combining cefixime 1, isothiocyanates 2, and alkyl bromides 3. The reaction was carried out in water at ambient temperature, using Cu@KF/CP NPs as a highly effective catalyst, leading to excellent yields. Moreover, the study findings showed that the synthesized compounds demonstrated a significant antioxidant activity compared to conventional antioxidants. The antibacterial efficacy of the synthesized compounds was evaluated against both Gram-positive and Gram-negative bacteria. Furthermore, Cu@KF/CP nanoparticles were utilized to adsorb CFX and 4-NP from water-based solutions. CONCLUSION: This study showcases the effective synthesis of innovative iminothiazole derivatives through the use of multicomponent reactions, involving the combination of cefixime, isothiocyanates, and alkyl bromides. The reactions were conducted in a water-based solvent. The reactions were carried out at room temperature, utilizing Cu@KF/CP NPs as catalysts. The Cu@KF/CP nanoparticles, a newly developed heterogeneous nanocatalyst, were synthesized and evaluated utilizing X-ray diffraction (XRD), fieldemission scanning electron microscopy (FESEM), energy-dispersive X-ray spectroscopy (EDX), and transmission electron microscopy (TEM) research techniques. Cu@KF/CP nanoparticles are utilized to adsorb CFX and 4-NP from water-based solutions. The objects were manufactured using a straightforward and uncomplicated approach. The BET surface area of Cu@KF/CP NPs was measured to be 201.8 m2/g. The experimental equilibrium data was evaluated by applying the isotherms of the Langmuir, Freundlich, Dubinin-Radushkevich, and Redlich-Peterson models. Additionally, we examined the catalytic efficiency of Cu@KF/CP nanoparticles (NPs) in reducing various colors in water.

Electrochemical, surface, and theoretical investigations of palm kernel shell extract as an effective inhibitor for carbon-steel corrosion in 1 M HCl solution.

Herein, we employed palm kernel shell extract (PKSE) as an eco-friendly inhibitor for carbon steel in acidic-induced corrosion. The corrosion inhibition of PKSE on carbon steel in 1 M HCI solution was investigated by electrochemical impedance spectroscopy, weight loss, and potentiodynamic polarization measurements. The surface was characterized by scanning electron microscopy equipped with energy-dispersive X-ray spectroscopy. Moreover, the elastic modulus and hardness tests were conducted. Weight loss measurements revealed that the optimum concentration of inhibitors is 500 ppm with 95.3% inhibition efficiency in 1 M HCl solution. Electrochemical results showed that the inhibitor could exhibit excellent corrosion inhibition performance and displayed mixed-type inhibition. The electrochemical impedance spectroscopy analysis shows that the inhibition performance increases by increasing the concentration of PKSE. The surface studies ensure the PKSE effectiveness in carbon steel surface damage reduction. Also, the adsorption of PKSE molecules on the carbon steel surface occurs according to the Langmuir isotherm model. The primary goal of this investigation was the utilization of palm kernel shell extract as corrosion inhibitor for 1018 low carbon steel in 1 M HCl solution, which highlights its novelty. The present results will be helpful to uncover the versatile importance of palm kernel shell compounds in the corrosion inhibition process.

Synbiotic effects of Lactobacillus plantarum CMT1 and Morinda citrifolia on the growth performance and disease resistance of whiteleg shrimp.

This study assesses the effects of a prebiotic derived from Morinda citrifolia (noni fruit) extract and a probiotic of Lactobacillus plantarum CMT1 alone and in combination on the survival, growth performance, digestive enzymes, and disease resistance of whiteleg shrimp. A total of 1200 juvenile shrimp were randomly allocated to four treatments: control (not supplemented with noni fruit extract or L. plantarum CMT1), Treatment 1 (TRT1) (supplemented with 1 % noni fruit extract), Treatment 2 (TRT2) (supplemented with 108 CFU/kg L. plantarum CMT1), and Treatment 3 (TRT3) (supplemented with 1 % noni fruit extract and 108 CFU/kg L. plantarum CMT1). After 56 days of feeding, the growth indices of the TRT3 group were statistically larger than the other treatments (P < 0.05). Shrimp in the three treatment groups demonstrated significantly enhanced survival compared to those in the control group (P < 0.05), but no significant differences were observed among these three groups (P > 0.05). Shrimp fed the TRT3 diet had the lowest feed conversion rate, which was statistically significant compared to the other groups. Shrimp in the TRT3 group also had significantly higher amylase and protease levels than the control group. In addition, the use of fruit extract or L.plantarum CMT1 alone and in combination significantly increased shrimp survival after exposure to Vibrio parahaemolyticus, with the TRT3 group recording the highest value. The results indicate that a synbiotic of M. citrifolia extract and L.plantarum CMT1 could be used in shrimp aquaculture to promote animal development and health.

Inhibition of Benzo[a]pyrene-induced DNA Adduct in Buccal Cells of Smokers by Black Raspberry Lozenges.

Using LC-MS/MS analysis we previously showed for the first time (Carcinogenesis 43:746-753, 2022) that levels of DNA damage-induced by benzo[a]pyrene (B[a]P), an oral carcinogen and tobacco smoke (TS) constituent, were significantly higher in buccal cells of smokers than those in non-smokers; these results suggest the potential contribution of B[a]P in the development of oral squamous cell carcinoma (OSCC) in humans. Treating cancers, including OSCC at late stages even with improved targeted therapies, continues to be a major challenge. Thus interception/prevention remains a preferable approach for OSCC management and control. In previous preclinical studies we and others demonstrated the protective effects of black raspberry (BRB) against carcinogen-induced DNA damage and OSCC. Thus, to translate preclinical findings we tested the hypothesis, in a Phase 0 clinical study, that BRB administration reduces DNA damage induced by B[a]P in buccal cells of smokers. After enrolling 27 smokers, baseline buccal cells were collected before the administration of BRB lozenges (5/day for 8 weeks, 1 gm BRB powder/lozenge) at baseline, at the middle and the end of BRB administration. The last samples were collected at four weeks after BRB cessation (washout period). B[a]P-induced DNA damage (BPDE-N2-dG) was evaluated by LC-MS/MS. BRB administration resulted in a significant reduction in DNA damage: 26.3% at the midpoint (p = 0.01506) compared to baseline, 36.1% at the end of BRB administration (p = 0.00355), and 16.6% after BRB cessation (p = 0.007586). Our results suggest the potential benefits of BRB as a chemopreventive agent against the development of TS-initiated OSCC.

Immunomodulatory effects and multi-omics analysis of Codonopsis Pilosula Extract in septic rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Codonopsis Pilosula (CP), as a well-known traditional Chinese medicine (TCM) with medicinal and edible herb, is one of the most representative tonic Chinese herbal medicine. It has been widely used for regulating immune function with hardly any adverse effects in clinical practice. AIM OF THE STUDY: This study aimed to elucidate the immunomodulatory effect and to explore probable mechanism of Codonopsis Pilosula Extract (CPE) in septic rats. MATERIALS AND METHODS: The model of septic rat was established by cecal ligation and perforation (CLP). The thymus index, spleen index and cerebral index were calculated. Histological changes were observed by Hematoxylin-eosin (HE). The positive expression of CD4+ T cells was determined in the thymus and spleen by immunohistochemical (IHC). The expression level of 24 h CD4 was corroborated by real-time quantitative polymerase chain reaction (RT-QPCR). Infectious factors, immune factors and inflammatory factors were determined by enzyme-linked immunosorbent assay (ELISA). Blood cells were detected by automatic biochemical analyzer. The metabolite changes and gene expression levels, the potential targets and pathways of CPE in regulating immune function of thymus were analyzed by integrative analysis of transcriptomic and metabolomic methods. RESULTS: High dose of CPE increased the thymus index and spleen index of septic rats at different stages, and the brain index at different stages could be increased at medium dose and high dose. Medium and high doses of CPE reduced the pathological changes of thymus, spleen and brain tissue. CPE promoted the expression levels of CD4 in the thymus and spleen. CPE improved the levels of red blood cells (RBC), lymphocytes (LYM) and hemoglobin (HGB), and decreased the levels of neutrophils (NEUT), NLR (NEUT/LYM) and PLR (PLT/LYM). CPE dynamically regulated the levels of white blood cells (WBC) and PLT (platelet). CPE dynamically regulated the expression levels of infectious factors, immune factors, and inflammatory factors related to disease severity. CONCLUSION: CPE has the ability to dynamically modulate the expression levels of infectious factors, immune factors, and inflammatory factors related to disease severity, and alleviate the damages of immune organs. The research has provided a global view of the integration of metabolomics and transcriptomics to elucidate the immunomodulatory effects and mechanisms of CPE. CPE could affect a series of biological processes in glycerophospholipid metabolism by interfering with the B cell receptor (BCR) signaling pathway in the thymus, to maintain immune homeostasis of septic rats on the whole, especially humoral immunity.

Ethanolic Extract from Echinacea purpurea (L.) Moench Inhibits Influenza A/B and Respiratory Syncytial Virus Infection in vitro: Preventive Agent for Viral Respiratory Infections.

Among the most frequent causes of respiratory infections in humans are influenza A virus H1N1 (H1N1), influenza B virus (IVB), and respiratory syncytial virus (RSV). Echinacea is a perennial wildflower belonging to the Asteraceae family. Echinacea purpurea (L.) Moench is a species belonging to the Echinacea genus. Its characteristic compound, chicoric acid (CA), is known for its physiological activities, including antiviral effects and immune enhancement. Activities of E. purpurea 60% ethanol extract (EPE) and CA in inhibiting infections caused by H1N1, IVB, and RSV subtype A (RSV-A) were evaluated through plaque inhibition tests, quantification of viral gene expression, and analysis of transmission electron microscopy (TEM) images. Additionally, inhibitory activities of EPE and CA for hemagglutination and neuraminidase (NA) of H1N1 and IVB were determined. In the plaque reduction assays, both EPE and CA reduced infectivity against H1N1, IVB, and RSV-A. Furthermore, quantitative real-time polymerase chain reaction analysis revealed that EPE and CA reduced gene expression levels for H1N1, IVB, and RSV-A, whereas TEM image analysis confirmed their inhibitory effects on host cell infection by these viruses. Hemagglutination assays exhibited the ability of EPE and CA to hinder H1N1 and IVB attachment to host cell receptors. Furthermore, EPE and CA displayed inhibition activity against the NA of H1N1 and IVB. These findings suggest that EPE and CA can suppress the infection and propagation of H1N1, IVB, and RSV-A, demonstrating their potential as preventive and therapeutic agents for viral respiratory infections or as ingredients for health functional foods.

Study on Translational toxicology of Senna obtusifolia aqueous extract.

In recent years, the clinical adverse drug reactions (ADR) reports of Senna obtusifolia have been constantly emerging, especially hepatotoxicity. However, it is unclear whether the liver is the only or main toxic target organ. In this study, we conducted a repeated administration experiment with the Senna obtusifolia Aqueous Extract (SE) and PCA analysis was used to determine the primary toxic target organs. The results revealed that the liver was the main toxic target organ and we also verifid the hepatotoxicity in vitro. The mechanism of hepatotoxicity was predicted by network toxicology technology, which was verified by ELISA, qPCR, western blotting and other methods.The results showed that SE could increase the serum levels of TNF-α, IL-6, IL-1ß, the mRNA expression levels of ACT1, TRAF6, NF-κB P65 and the protein expression levels of TRAF6, NF-κB P65, P-P65 in rat livers and HepG2 cells, which indicated that SE induced hepatotoxicity might be related to inflammatory response.

The effects of green coffee bean extract on blood pressure and heart rate: A systematic review and dose-response meta-analysis of randomized controlled trials.

BACKGROUND AND AIMS: The existing literature on the effects of green coffee bean extract (GCBE) consumption on systolic blood pressure (SBP), diastolic blood pressure (DBP), and heart rate (HR) is equivocal. This study aimed to summarize the effects of GCBE consumption on SBP, DBP and HR in adults. METHODS: Data were pooled using a random-effects model and expressed as weighted mean difference (WMD) and 95 % confidence intervals (95 % CIs). RESULTS: Out of 1624 records, 10 studies that enrolled 563 participants were included. GCBE consumption significantly decreased SBP (WMD: -2.95 mmHg; 95 % CI: -4.27 to -1.62; p < 0.001) and DBP (WMD: -2.15 mmHg; 95 % CI: -2.59 to -1.72; p < 0.001). However, there was no significant effect on HR (WMD: -1.20 bpm; CI: -2.93 to 0.51; p = 0.170). Subgroup analysis showed that GCBE consumption had a more significant effect on SBP and DBP in participants with high SBP and DBP and had no effect on blood pressure in females. Linear and non-linear dose-response analyses were conducted to find the optimum GCBE dosage and duration of intervention. However, no significant associations were observed for SBP, DBP, and HR in linear meta-regression and non-linear dose-response based on the dose and duration of the intervention. CONCLUSION: GCBE has the potential as a hypertension-reducing supplement in hypertensive patients. However, GCBE did not significantly change HR.

Antibacterial gelatin/tragacanth gum films containing galbanum essential oil for in vitro scratch-healing.

Natural substances and bioactive agents possess great potential in wound care based on their ability to promote healing and prevent infection. This study focused on the fabrication of antibacterial wound dressings by combining gelatin (G), tragacanth gum (TG), and galbanum essential oil (GEO) as a loaded drug. TG addition resulted in more elastic and flexible films besides enabling encapsulation of the hydrophobic GEO into the biopolymeric matrix. GEO was utilized as an antibacterial and a wound-healing enhancer for open wounds such as incisions. Field emission scanning electron microscopy (FE-SEM) analysis revealed a porous film structure after GEO incorporation. Higher GEO concentration caused reduced swelling and slower degradation. Water vapor transfer rate varied from 596 to 894 g/m2.day, making the films suitable for wound dressings. GEO release exhibited a two-phase profile with prolonged diffusion-controlled release for a higher content of GEO. The films demonstrated dose-dependent antimicrobial activity against S. aureus and E. coli strains. Effectiveness and noteworthy application of this research were approved by scratch assay on human dermal fibroblast cells, and films with 3 % GEO showed 79.42 % wound closure, which is significantly higher than the control sample (55.15 %), indicating promoted cell migration and promising wound healing properties.

Optimization and pharmacological evaluation of phytochemical-rich Cuscuta reflexa seed extract for its efficacy against chlorpyrifos-induced hepatotoxicity in murine models.

The popular organophosphorus (OP) compound chlorpyrifos (CP) has recently gained significant attention due to its health risks, particularly among farmers exposed to OP pesticides. This study aimed to evaluate the acute toxicity of Cuscuta reflexa seed extract (CRSE) and its efficacy of mitigating the adverse effects of CP in albino male mice. For acute toxicity analysis, the first group was served as the control group, while the second group was received CRSE (200 mg/kg/bw) on the first day of the 14-day experiment. For hepatotoxicity analysis, the first group was the control group, the second group (vehicle control) received corn oil (CO) (2 mL/kg/bw), the third group was given CP (20 mg/kg/bw) dissolved in corn oil and the fourth group was given CP (20 mg/kg/bw) along-with CRSE (200 mg/kg/bw) orally via gavage once daily for 21 days. The acute toxicity examination revealed no statistically significant differences between the CRSE-treated and control groups in serum biochemical indicators and histopathological analyses of various organs, suggesting that CRSE as safe at a dosage of 200 mg/kg/bw, with an oral LD50 in mice higher than 200 mg/kg. The hepatotoxicity study demonstrated that the CP administration resulted in liver damage and oxidative stress, while CRSE acted as an antioxidant and attenuated the signs of oxidative stress in liver damage. Hence, a promising therapeutic approach for lowering CP hepatotoxicity is co-treatment with CRSE.

Biofabrication of Nanosilver From Punica granatum Peel Extract and Their Anticoagulant Applications.

For utilizing biodegradable waste as a natural source for nanofabrication, this study was designed to highlight a simple, sustainable, safe, environmentally friendly, and energy consumption reduction waste management approach using hot aqueous extract of Punica granatum (pomegranate) peel waste (PPE) to biosynthesize silver nanoparticles (PPE-AgNPs). The fabrication of biosynthesized nanosilver was confirmed by UV-visible spectroscopy, scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDX), X-ray diffraction (XRD), and atomic force microscope (AFM). The initial pale brown color change upon adding silver nitrate to PPE confirmed bioreduction. For PPE, the absorption spectrum for UV-vis spectroscopy in the visible light region was 230-290 nm, while for PPE-AgNPs, the graph shows that surface plasmon resonance (SPR) spectrum for nanosilver at 360-460 nm. The XRD analysis proved that the PPE-AgNPs were crystalline in nature. The SEM micrograph revealed that silver nanoparticles were sphere-shaped, homogenous accumulations with particle size in the range of 21.63-30.97 ± 0.4 nm. The EDX data analysis also proved the presence of a sharp peak of silver element with 8.83% weight at 3 keV. The 3D AFM images of Ag nanoparticles illustrated that the diameter is around 7.20-14.80 nm with a median of 7.16 ± 1.3 nm and the root mean square (RMS) value corresponds to 1.40 ± 0.4 nm. The PPE-AgNPs efficiently exhibited a potent antioxidant and dose-dependent DPPH inhibition action. Visual and microscopic observations of fresh human blood when treated with 25, 50, 75, and 100 µg/mL of PPE-AgNPs were proven to be biocompatible with no morphological changes and no coagulation. This study predicts that PPE can be utilized to synthesize biocompatible nanosilver.