Effects of Ocimum basilicum essential oil and ginger extract on serum biochemistry, oxidative stress and gill tissue damage of pearl gentian grouper during simulated live transport.

This study explored the effects of the essential oil of Ocimum basilicum (EOOB) and ginger extract (GE) during the transportation of pearl gentian grouper from water quality, serum biochemistry, oxidative stress, meat flavor, and gill tissue morphology. Fish (450 ± 50 g) were allocated to the following 5 treatments: control group (fish transported in water only), 5 mg/LEOOB, 10 mg/LEOOB, 3 mg/LGE, and 6 mg/LGE and transported in insulation boxes (66 × 51 × 37.8 cm) for 72 h. Samples were taken at 0, 12, 36, 60, and 72 h immediately after transport. It was found that 10 mg/LEOOB and 6 mg/LGE could reduce the levels of total ammonia nitrogen (TAN), dissolved oxygen (DO), water pH, serum glucose (GLU), cortisol (COR), liver superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA), and glutathione peroxidase (GPX), increase the activities of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH), as well as significantly increase the total free amino acid (TFAA) content in muscle compared to the control group (P < 0.05). In addition, by observing the microstructure of gill tissue, it was found that compared with untreated grouper, the morphological damage of gill tissue in EOOB and GE treatment was alleviated. These results indicated that adding appropriate amounts of EOOB and GE to transport water could improve the water quality, relieve stress, and lower energy metabolism of grouper during transport. The results of this research will help to improve the survival rate of grouper after transportation and decrease economic losses to fishery.

A Dietary Source of High Level of Fluoroquinolone Tolerance in mcr-Carrying Gram-Negative Bacteria.

The emergence of antibiotic tolerance, characterized by the prolonged survival of bacteria following antibiotic exposure, in natural bacterial populations, especially in pathogens carrying antibiotic resistance genes, has been an increasing threat to public health. However, the major causes contributing to the formation of antibiotic tolerance and underlying molecular mechanisms are yet poorly understood. Herein, we show that potassium sorbate (PS), a widely used food additive, triggers a high level of fluoroquinolone tolerance in bacteria carrying mobile colistin resistance gene mcr. Mechanistic studies demonstrate that PS treatment results in the accumulation of intracellular fumarate, which activates bacterial two-component system and decreases the expression level of outer membrane protein OmpF, thereby reducing the uptake of ciprofloxacin. In addition, the supplementation of PS inhibits aerobic respiration, reduces reactive oxygen species production and alleviates DNA damage caused by bactericidal antibiotics. Furthermore, we demonstrate that succinate, an intermediate product of the tricarboxylic acid cycle, overcomes PS-mediated ciprofloxacin tolerance. In multiple animal models, ciprofloxacin treatment displays failure outcomes in PS preadministrated animals, including comparable survival and bacterial loads with the vehicle group. Taken together, our works offer novel mechanistic insights into the development of antibiotic tolerance and uncover potential risks associated with PS use.

Sustainable conversion of cottonseed hulls to valuable proanthocyanidins through ultrasound-assisted deep eutectic solvent extraction.

This study presents a novel approach for converting cottonseed hulls (CSHs) into valuable proanthocyanidins (PAs) through deep eutectic solvent (DES)-based ultrasound-assisted extraction (UAE-DES). Response surface methodology (RSM) was applied to optimize and model this process, resulting in maximum yields of 78.58 mg/g. The ideal PA extraction conditions were determined to be a liquid-to-material ratio of 36.25 mL/g, a water content of 33.21%, and an extraction period of 7.4 min. Molecular dynamic simulations (MDS) were performed to study the interactions between the solvent and target chemicals. Increased van der Waals forces and stronger interactions between DES and the target chemical catechin (CA) compared to those observed with methanol or water were observed. Furthermore, the optimized extract exhibited a higher PA content than can be obtained with conventional extraction methods and demonstrated antioxidant activity in vitro. The cottonseed hulls residues (CSRs) remaining after the extraction process can be used to produce activated carbon (ACCSR), which has some capacity to adsorb methylene blue (MB) contaminants. This study offers a reference for the fruitful transformation of waste biomass into high-value products.

Nanomotors-loaded microneedle patches for the treatment of bacterial biofilm-related infections of wound.

The biofilms formed by bacteria at the wound site can effectively protect the bacteria, which greatly weakens the effect of antibiotics. Herein, a microneedle patch for wound treatment is designed, which can effectively penetrate the biofilms in a physical way because of the penetration ability of the microneedles and the motion behavior of the nanomotors, and deliver bacterial quorum sensing inhibitor luteolin (Le) and nanomotors with multiple antibacterial properties within biofilms. Firstly, the nanomotors-loaded microneedle patches are prepared and characterized. The results of in vitro and in vivo experiments show that the microneedle patches have good biosafety and antibacterial properties. Among them, Le can inhibit the growth of biofilms. Further, under near-infrared (NIR) irradiation, the nanomotors loaded with photosensitizer ICG and nitric oxide (NO) donor L-arginine (L-Arg) can move in the biofilms under the double driving effect of photothermal and NO, and can give full play to the multiple anti-biological infection effects of photothermal therapy (PTT), photodynamic therapy (PDT) and NO, and finally realize the effective removal of biofilms and promote wound healing. The intervention of nanomotor technology has brought about a new therapeutic strategy for bacterial biofilm-related infection of wound.

Comparison of the effect of extraction methods on waste cotton (Gossypium hirsutum L.) flowers: metabolic profile, bioactive components, antioxidant, and α-amylase inhibition.

BACKGROUND: Waste cotton flowers, as a by-product of cotton cultivation, are enriched with bioactive substances that render them a promising natural source of health-promoting benefits. In this study, ultrasound-assisted extraction (UAE), subcritical water extraction (SWE), and conventional extraction (CE) approaches were applied to extract bioactive compounds from waste cotton flowers, and the metabolic profiles, bioactive components, antioxidants, and α-amylase inhibition of different extractions were systematically analyzed and compared. RESULTS: It was observed that UAE and CE extracts had similar metabolic profiles compared with SWE. The flavonoids and amino acids and derivatives were more prone to be extracted by UAE and CE, whereas phenolic acids tended to accumulate in SWE extract. The UAE extract had the highest amounts of total polyphenols (214.07 mg gallic acid equivalents per gram dry weight) and flavonoids (33.23 mg rutin equivalents per gram dry weight) as well as the strongest inhibition on oxidation (IC50 = 10.80 µg mL-1 ) and α-amylase activity (IC50 = 0.62 mg mL-1 ), indicating that chemical composition was closely related to biological activity. Additionally, microstructures and thermal behaviors of the extracts were investigated and highlighted the ability of UAE. CONCLUSION: Overall, it can be concluded that UAE is an efficient, green, and economical extraction method to produce bioactive compounds from cotton flowers, and the UAE extracts could be used in food and medicine industries because of their high antioxidant and α-amylase inhibitory activity. This study provides a scientific basis for the development and comprehensive utilization of cotton by-products. © 2023 Society of Chemical Industry.

Effectiveness of Scutellaria baicalensis Georgi root in pregnancy-related diseases: A review.

The root of Scutellaria baicalensis Georgi, also called Huangqin, is frequently used in traditional Chinese medicine. In ancient China, S. baicalensis root was used to clear heat, protect the fetus, and avoid a miscarriage for thousands of years. In modern times, pregnancy-related diseases can seriously affect maternal and fetal health, but few systematic studies have explored the mechanisms and potential targets of S. baicalensis root in the treatment of pregnancy-related diseases. Flavonoids (baicalein, wogonin and oroxylin A) and flavonoid glycosides (baicalin and wogonoside) are the main chemical components in the root of S. baicalensis. This study presents the current understanding of the major chemical components in the root of S. baicalensis, focusing on their traditional uses, potential therapeutic effects and ethnopharmacological relevance to pregnancy-related disorders. The mechanisms, potential targets and experimental models of S. baicalensis root for ameliorating pregnancy-related diseases, such as recurrent spontaneous abortion, preeclampsia, preterm birth, fetal growth restriction and gestational diabetes mellitus, are highlighted.

Simultaneous Determination of Seven Phenolic Acids, Two Flavonoids, and Tussilagone in Rat Plasma after Administration of Farfarae Flos Extract by LC-MS/MS.

A simple LC-MS/MS method was established for the simultaneous quantitative analysis of concentration of seven phenolic acids, two flavonoids, and tussilagone in biological samples. The lower limit of quantitation of each target compound was less than 10 ng·mL-1. The precision of these three types of compounds was less than 15%, and all accuracy was between 85.9% and 115%. The preliminary pharmacokinetics of these three types of compounds in plasma samples were carried out using LC-MS/MS after administration of Farfarae Flos extract (3.90 and 7.80 g·kg-1) to rats, respectively. The results showed that T max of all ten compounds varied from 0.21 ± 0.04 h to 0.69 ± 0.19 h. Maximum concentrations and area under concentration-time curves of seven analyzed phenolic acids were higher than those of the two flavonoids and tussilagone. Terminal elimination half-life of tussilagone was the shortest among these three types of compounds. The results showed that the developed LC-MS/MS method was suitable for clarifying the pharmacokinetic characteristics of these three types of compounds in plasma after administration of Farfarae Flos extract in rats.

Sodium dehydroacetate confers broad antibiotic tolerance by remodeling bacterial metabolism.

Antibiotic tolerance has been a growing crisis that is seriously threatening global public health. However, little is known about the exogenous factors capable of triggering the development of antibiotic tolerance, particularly in vivo. Here we uncovered that an previously approved food additive termed sodium dehydroacetate (DHA-S) supplementation remarkably impaired the activity of bactericidal antibiotics against various bacterial pathogens. Mechanistic studies indicated that DHA-S induced glyoxylate shunt and reduced bacterial cellular respiration by inhibiting the enzymatic activity of α-ketoglutarate dehydrogenase (α-KGDH). Furthermore, DHA-S mitigated oxidative stress imposed by bactericidal antibiotics and enhanced the function of multidrug efflux pumps. These actions worked together to induce bacterial tolerance to antibiotic killing. Interestingly, the addition of five exogenous amino acids, particularly cysteine and proline, effectively reversed antibiotic tolerance elicited by DHA-S both in vitro and in mouse models of infection. Taken together, these findings advance our understanding of the potential risks of DHA-S in the treatment of bacterial infections, and shed new insights into the relationships between antibiotic tolerance and bacterial metabolism.

An Exploratory Cohort Study of the Association between the Level of Testosterone and Suicidal Ideation in Hospitalized Adolescent Females with Depression in China.

BACKGROUND: To date, around 4 per 100,000 adolescents committed suicide within the 29 OECD countries. The suicidal behavior is related to psychological factors, genetics, neurobiology, and other biomarkers. The aim of this study was to examine risk factors for the development of suicidal ideation in adolescent females with depression, focusing on the relationship between different testosterone levels and suicidal ideation, in order to help develop strategies to intervene in suicidal behavior in female adolescents with depression. METHOD: In this single-center prospective cohort study, we enrolled adolescent females with depression. We collected information on their baseline data, testosterone levels, symptom self-rating scale scores, suicidal ideation, non-suicidal self-injurious (NSSI) behaviours, and suicide attempts. We used multivariate logistic regression to identify risk factors for the development of suicidal ideation in adolescent females with depression. RESULTS: A total of 113 hospitalized adolescent females were enrolled with a mean age of 13.5 (1.20). Among these patients, there were 86 (76.11%) subjects who suffered from suicidal ideation, 59 (52.21%) had NSSI and 23 (20.35%) had suicide attempt behavior. In the final model, higher level of testosterone (p=0.04) and higher age (p=0.02) were associated with the higher odds of having suicidal ideation. CONCLUSION: In this exploratory cohort study, the emergence of suicidal ideation was common among adolescent females with depression. This study is consistent with the other studies. It shows that the age is a potential predictor for suicidal ideation in hospitalized adolescent females with depression.

Gentiana scabra Restrains Hepatic Pro-Inflammatory Macrophages to Ameliorate Non-Alcoholic Fatty Liver Disease.

Non-alcoholic fatty liver disease (NAFLD) has become a progressive metabolic disease that is emerging as a global epidemic. Considering that the complex pathogenesis has not been fully elucidated, barely specific pharmacological therapy is recommended in current guidelines. Gentiana scabra (GS) is a commonly used herb in Tibetan medicine, which has received much attention in recent years due to its diverse pharmacological properties, including anti-inflammation, anti-oxidation, and anti-fibrosis. However, the therapeutic mechanisms are still unclear. Our investigation demonstrated a regulatory effect of GS on pro-inflammatory macrophages, which was extensively investigated in NAFLD that revealed intimate participation in the disease evolution, and the non-canonical IKK family member TANK-binding kinase 1 (TBK1) was involved in this process. Plasmid vectors for shTBK1 and amlexanox (AML), an inhibitor of TBK1, were used in this study to verify the mechanisms of TBK1 both in vitro and in vivo, while a co-culture system for hepatocytes and BMDMs was constructed to confirm the critical role of macrophages for inflammatory cascade. The results revealed that metabolic burden up-regulated the phosphorylation of TBK1, resulting in activation of NF-κB signaling pathway, and consequently caused an elevated expression of MCP1 to induce the macrophage recruitment and accelerate the inflammatory cascade. In contrast, GS could inhibit the TBK1 phosphorylation and the MCP1 expression to restrain the recruitment of pro-inflammatory macrophages, so as to provide curative effects on metabolic dysfunction and inflammation. Considering that GS is non-toxic and can be used as a kind of tea for long-term drinking, we propose it may be an effective option for the prevention and treatment of NAFLD, which deserves further exploration and application, and may provide new insights to improve the current standardized intervention strategy.

Simultaneous determination of six synthetic phenolic antioxidants in edible oils using dispersive liquid-liquid microextraction followed by high-performance liquid chromatography with diode array detection.

A simple, rapid, organic-solvent- and sample-saving pretreatment technique, called dispersive liquid-liquid microextraction, was developed for the determination of six synthetic phenolic antioxidants from edible oils before high-performance liquid chromatography with diode array detection. The entire procedure was composed of a two-step microextraction and a centrifugal process and could be finished in about 5 min, only consuming only 25 mg of sample and 1 mL of the organic solvent for each extraction. The influences of several important parameters on the microextraction efficiency were thoroughly investigated. Recovery assays for oil samples were spiked at three concentration levels, 50, 100 and 200 mg/kg, and provided recoveries in the 86.3-102.5% range with a relative standard deviation below 3.5%. The intra-day and inter-day precisions for the analysis were less than 3.8%. The proposed method was successfully applied for the determination of synthetic phenolic antioxidants in different oil samples, and satisfactory results were obtained. Thus, the developed method represents a viable alternative for the quality control of synthetic phenolic antioxidant concentrations in edible oils.

[Effect of crucumin on vascular endothelial function in atherosclerotic rabbits].

OBJECTIVE: To observe the effect of curcumin on nitric oxide (NO) in plasma of atherosclerotic rabbits, activity of constitutive nitric oxide synthase (cNOS) and asymmetric dimethylarginine (ADMA), and discuss curcumin's effect against AS and its correlation with ADMA. METHOD: Thirty-eight male Japanese white rabbits were randomly divided into four groups: the control group (eight rabbits fed with standard diets), the model group (ten rabbits fed with high-fat diets), the low dose curcumin group (ten rabbits fed with high-fat diets and 100 mg . kg-1 d -1 ) and the high dose curcumin group (ten rabbits fed with high-fat diets and 200 mg kg-1 d-1 curcumin). At the end of the 12th week, their plasmas were tested for TC, LDL-C, NO, endothelin (ET) , ADMA and activity of aortic cNOS. Aortic tissues were collected for histological examinations. RESULT: The three groups fed with high-fat diets showed higher plasma ADMA and ET than the control group (P <0. 01) , but with decrease in plasma NO concentration and arterial cNOS activity (P <0. 01). Compared with the model group (P <0. 05) , the curcumin groups showed lower plasma ADMA and ET (P <0. 05), but higher plasma NO concentration and arterial cNOS activity than the model group (P <0. 01). There was no significant difference between the two curcumin groups. CONCLUSION: Curcumin may play an important protective role in AS process by reducing plasma ADMA level. [Key words] atherosclerosis; asymmetric dimethylarginine; crucumin; nitric oxide; nitric oxide synthase

HCV peptide (C5A), an amphipathic α-helical peptide of hepatitis virus C, is an activator of N-formyl peptide receptor in human phagocytes.

The hepatitis C virus (HCV) nonstructural 5A, a phosphorylated zinc metalloprotein, is an essential component of the HCV replication complex. An amphipathic α-helical peptide (HCV peptide [C5A]) derived from nonstructural 5A membrane anchor domain possesses potent anti-HCV and anti-HIV activity in vitro. In this study, we aimed to investigate the potential of HCV peptide (C5A) to regulate host immune responses. The capacity of HCV peptide (C5A) in vitro to induce migration and calcium mobilization of human phagocytes and chemoattractant receptor-transfected cells was investigated. The recruitment of phagocytes in vivo induced by HCV peptide (C5A) and its adjuvant activity were examined. The results revealed that HCV peptide (C5A) was a chemoattractant and activator of human phagocytic leukocytes by using a G-protein coupled receptor, namely formyl peptide receptor. In mice, HCV peptide (C5A) induced massive phagocyte infiltration after injection in the air pouch or the s.c. region. HCV peptide (C5A) also acted as an immune adjuvant by enhancing specific T cell responses to Ag challenge in mice. Our results suggest that HCV peptide (C5A) derived from HCV regulates innate and adaptive immunity in the host by activating the formyl peptide receptor.

The role of TLR2, TRL3, TRL4, and TRL9 signaling in the pathogenesis of autoimmune disease in a retinal autoimmunity model.

PURPOSE: Induction of tissue-specific experimental autoimmune diseases involves the use of complete Freund adjuvant containing Mycobacterium tuberculosis, whose recognition by the innate immune system depends on Toll-like receptors (TLRs) that signal through the adaptor molecule MyD88. The authors' previous study showed that MyD88(-/-) mice, but not TLR2(-/-), TLR4(-/-), or TLR9(-/-) mice, were resistant to experimental autoimmune uveitis (EAU). METHODS: The EAU induction in mice deficient in TLR3 or mice double deficient in TLR2+4, TLR2+9, and TLR4+9 was examined and the role of the TLR agonists in the adjuvant effect involved in the induction of EAU was assessed. RESULTS: TLR3-deficient and TLR2+4, TLR2+9, and TLR4+9 double-deficient mice were as susceptible to EAU as their control littermates. However, in mice immunized with a low-dose EAU regimen, TLR4 agonist lipopolysaccharide (LPS) enhanced EAU scores, delayed-type hypersensitivity responses, and antigen-specific T-cell proliferation. Antigen-specific IL-17 and IFN-gamma production by T lymphocytes was markedly increased in the LPS-treated group. The effects of LPS on EAU were abolished by treatment with an LPS deactivator polymyxin B. Inclusion of agonists for TLR2, TRL3, or TRL9 in immunization also enhanced EAU scores. CONCLUSIONS: These results suggest that signaling of TLR2, TRL3, TRL4, and TRL9 is highly redundant in the adjuvant effect needed to induce EAU and that diverse microbial infections may contribute to the pathogenesis of diseases such as uveitis.