Berberine promotes the degradation of phenylacetic acid to prevent thrombosis by modulating gut microbiota.

BACKGROUND: Berberine is the main bioactive constituent of Coptis chinensis, a quaternary ammonium alkaloid. While berberine's cardiovascular benefits are well-documented, its impact on thrombosis remains not fully understood. PURPOSE: This study investigates the potential of intestinal microbiota as a novel target for preventing thrombosis, with a focus on berberine, a natural compound known for its effectiveness in managing cardiovascular conditions. METHODS: Intraperitoneal injection of carrageenan induces the secretion of chemical mediators such as histamine and serotonin from mast cells to promote thrombosis. This model can directly and visually observe the progression of thrombosis in a time-dependent manner. Thrombosis was induced by intravenous injection of 1 % carrageenan solution (20 mg/kg) to all mice except the vehicle control group. Quantitative analysis of gut microbiota metabolites through LC/MS. Then, the gut microbiota of mice was analyzed using 16S rRNA sequencing to assess the changes. Finally, the effects of gut microbiota on thrombosis were explored by fecal microbiota transplantation. RESULTS: Our research shows that berberine inhibits thrombosis by altering intestinal microbiota composition and related metabolites. Notably, berberine curtails the biosynthesis of phenylacetylglycine, a thrombosis-promoting coproduct of the host-intestinal microbiota, by promoting phenylacetic acid degradation. This research underscores the significance of phenylacetylglycine as a thrombosis-promoting risk factor, as evidenced by the ability of intraperitoneal phenylacetylglycine injection to reverse berberine's efficacy. Fecal microbiota transplantation experiment confirms the crucial role of intestinal microbiota in thrombus formation. CONCLUSION: Initiating our investigation from the perspective of the gut microbiota, we have, for the first time, unveiled that berberine inhibits thrombus formation by promoting the degradation of phenylacetic acid, consequently suppressing the biosynthesis of PAG. This discovery further substantiates the intricate interplay between the gut microbiota and thrombosis. Our study advances the understanding that intestinal microbiota plays a crucial role in thrombosis development and highlights berberine-mediated intestinal microbiota modulation as a promising therapeutic approach for thrombosis prevention.

Protoberberine alkaloids: A review of the gastroprotective effects, pharmacokinetics, and toxicity.

BACKGROUND: Stomach diseases have become global health concerns. Protoberberine alkaloids (PBAs) are a group of quaternary isoquinoline alkaloids from abundant natural sources and have been shown to improve gastric disorders in preclinical and clinical studies. The finding that PBAs exhibit low oral bioavailability but potent pharmacological activity has attracted great interest. PURPOSE: This review aims to provide a systematic review of the molecular mechanisms of PBAs in the treatment of gastric disorders and to discuss the current understanding of the pharmacokinetics and toxicity of PBAs. METHODS: The articles related to PBAs were collected from the Web of Science, Pubmed, and China National Knowledge Infrastructure databases using relevant keywords. The collected articles were screened and categorized according to their research content to focus on the gastroprotective effects, pharmacokinetics, and toxicity of PBAs. RESULTS: Based on the results of preclinical studies, PBAs have demonstrated therapeutic effects on chronic atrophic gastritis and gastric cancer by activating interleukin-4 (IL-4)/signal transducer and activator of transcription 6 (STAT6) pathway and suppressing transforming growth factor-beta 1 (TGF-ß1)/phosphoinositide 3-kinase (PI3K), Janus kinase-2 (JAK2)/signal transducers and activators of transcription 3 (STAT3), and mitogen-activated protein kinase (MAPK) pathways. The major PBAs exhibit similar pharmacokinetic properties, including rapid absorption, slow elimination, and low bioavailability. Notably, the natural organ-targeting property of PBAs may account for the finding of their low blood levels and high pharmacological activity. PBAs interact with other compounds, including conventional drugs and natural products, by modulation of metabolic enzymes and transporters. The potential tissue toxicity of PBAs should be emphasized due to their high tissue accumulation. CONCLUSION: This review highlights the gastroprotective effects, pharmacokinetics, and toxicity of PBAs and will contribute to the evaluation of drug properties and clinical translational studies of PBAs, accelerating their transfer from the laboratory to the bedside.

Mechanisms and regulation of defensins in host defense.

As a family of cationic host defense peptides, defensins are mainly synthesized by Paneth cells, neutrophils, and epithelial cells, contributing to host defense. Their biological functions in innate immunity, as well as their structure and activity relationships, along with their mechanisms of action and therapeutic potential, have been of great interest in recent years. To highlight the key research into the role of defensins in human and animal health, we first describe their research history, structural features, evolution, and antimicrobial mechanisms. Next, we cover the role of defensins in immune homeostasis, chemotaxis, mucosal barrier function, gut microbiota regulation, intestinal development and regulation of cell death. Further, we discuss their clinical relevance and therapeutic potential in various diseases, including infectious disease, inflammatory bowel disease, diabetes and obesity, chronic inflammatory lung disease, periodontitis and cancer. Finally, we summarize the current knowledge regarding the nutrient-dependent regulation of defensins, including fatty acids, amino acids, microelements, plant extracts, and probiotics, while considering the clinical application of such regulation. Together, the review summarizes the various biological functions, mechanism of actions and potential clinical significance of defensins, along with the challenges in developing defensins-based therapy, thus providing crucial insights into their biology and potential clinical utility.

[Cervical spondylosis of nerve root type with qi stagnation and blood stasis treated with warming needle with different lengths of moxa stick: a randomized controlled trial].

OBJECTIVE: To compare the clinical efficacy on cervical spondylosis of nerve root type with qi stagnation and blood stasis treated with warming needle with different lengths of moxa stick. METHODS: Six hundred patients with cervical spondylosis of nerve root type with qi stagnation and blood stasis were randomly divided into 4 groups: a 4 cm length group (150 cases, 5 cases dropped off, 2 cases suspended), a 3 cm length group (150 cases, 6 cases dropped off, 2 cases suspended), a 2 cm length group (150 cases, 6 cases dropped off), and a routine acupuncture group (150 cases, 6 cases dropped off). Warming needle with moxa stick in the length of 4 cm, 3 cm and 2 cm was delivered in the 4 cm length group, the 3 cm length group and the 2 cm length group, respectively. In the routine acupuncture group, simple acupuncture was applied. The acupoints selected in the above groups included Dazhui (GV 14) and bilateral Jiaji (EX-B 2) of C5 and C7, Fengchi (GB 20), Jianzhen (SI 9), Quchi (LI 11), Zhongzhu (TE 3), etc. In each group, the intervention was delivered once daily and 5 times a week. One course of intervention was composed of 2 weeks and 2 courses were required. The TCM syndrome score, the score of clinical assessment scale for cervical spondylosis (CASCS), the score of the brachial plexus traction test of the affected upper limb, F wave occurrence rate and conduction velocity of the ulnar nerve, the median nerve and the radial nerve of the affected upper limb were compared before and after treatment in the patients of each group. The levels of serum inflammatory factors, i.e. interleukin-1ß (IL-1ß), interleukin-6 (IL-6), tumor necrosis factor α (TNF-α) and hypersensitive C-reactive protein (hs-CRP), were measured before and after treatment in the patients of each group. The clinical cfficacy was evaluated in the 4 groups. RESULTS: After treatment, the results of TCM syndrome evaluation, i.e. the scores of neck pain, activity limitation and upper limb numbness and pain, as well as the total scores; and the scores of brachial plexus traction test were reduced when compared with those before treatment in each group (P<0.01, P<0.05). The scores of subjective symptoms and adaptability, and the total scores of CASCS were elevated in comparison with those before treatment in each group (P<0.01, P<0.05). In the 4 cm length group, compared with the other 3 groups, the scores of neck pain and activity limitation for TCM syndrome evaluation, and its total score were lower (P<0.05, P<0.01); and the scores of subjective symptoms and adaptability, and the total score of CASCS were higher (P<0.05, P<0.01). The score of the brachial plexus traction test in the 4 cm length group was lower than that of the routine acupuncture group (P<0.05). After treatment, F wave occurrence rates and conduction velocity of median nerve and radial nerve were increased when compared with those before treatment in each group (P<0.05, P<0.01). F wave occurrence rate and conduction velocity of the radial nerve in the 4 cm length group were higher than those of the other 3 groups (P<0.05), and those of the median nerve were higher when compared with the routine acupuncture group (P<0.05). After treatment, the levels of serum IL-1ß, IL-6 and TNF-α were all reduced when compared with those before treatment in each group (P<0.01, P<0.05); the level of serum IL-6 in the 4 cm length group was lower than those of the other 3 groups and serum level of TNF-α was lower compared with that in the routine acupuncture group (P<0.05). The total effective rate of the 4 cm length group was 78.3% (112/143), which was higher when compared with the 3 cm length group (67.6%, 96/142), the 2 cm length group (65.3%, 94/144) and the routine acupuncture group (53.5%, 77/144), respectively (P<0.05). CONCLUSION: Warming needle with moxa stick of 4 cm in length effectively relieves the clinical symptoms of cervical spondylosis of nerve root type with qi stagnation and blood stasis, improves the nerve function of the upper limbs, and reduces the inflammatory responses caused by nerve compression. The clinical efficacy of this therapy with moxa stick of 4 cm in length is superior to the warming needle with moxa sticks of 3 cm and 2 cm, as well as the routine acupuncture.

Metabolites analysis of plantamajoside based on gut microbiota-drug interaction.

BACKGROUND: Plantaginis Herba (Plantago asiatica L.) has the effects of clearing heat and diuresis, oozing wet and drenching. As the main active components of Plantaginis Herba (Plantago asiatica L.), plantamajoside have a wide range of antitumor activities but very low bioavailability. The process of interacting between plantamajoside and gut microbiota remains unclear. PURPOSE: To illustrate the process of interacting between plantamajoside and gut microbiota based on high-resolution mass spectrometry and targeted metabolomics methods. STUDY DESIGN AND METHODS: This experiment was divided into two parts. First, metabolites produced from plantamajoside by gut microbiota were identified and quantified based on high-resolution mass spectrometry and LC-MS/MS. Additionally, stimulation of plantamajoside on gut microbiota-derived metabolites was determined by targeted metabolomics and gas chromatography. RESULTS: We first found that plantamajoside was rapidly metabolized by gut microbiota. Then, we identified metabolites of plantamajoside by high-resolution mass spectrometry and speculated that plantamajoside was metabolized into five metabolites including calceolarioside A, dopaol glucoside, hydroxytyrosol, 3-(3-hydroxyphenyl) propionic acid (3-HPP) and caffeic acid. Among them, we quantitatively analyzed four possible metabolites based on LC‒MS/MS and found that hydroxytyrosol and 3-HPP were final products by the gut microbiota. In addition, we studied whether plantamajoside could affect the short-chain fatty acid (SCFA) and amino acid metabolites. We found that plantamajoside could inhibit the acetic acid, kynurenic acid (KYNA) and kynurenine (KN) produced by intestinal bacteria and promote the indole propionic acid (IPA) and indole formaldehyde (IALD) produced by intestinal bacteria. CONCLUSION: An interaction between plantamajoside and gut microbiota was revealed in this study. Unlike the traditional metabolic system, the special metabolic characteristics of plantamajoside in gut microbiota was found. Plantamajoside was metabolized into the following active metabolites: calceolarioside A, dopaol glucoside, hydroxytyrosol, caffeic acid and 3-HPP. Besides, plantamajoside could affect SCFA and tryptophan metabolism by gut microbiota. Especially, the exogenous metabolites hydroxytyrosol, caffeic acid and endogenous metabolites IPA may have potential association with the antitumor activity of plantamajoside.

Gut microbiota-based metabolites of Xiaoyao Pills (a typical Traditional Chinese medicine) ameliorate depression by inhibiting fatty acid amide hydrolase levels in brain.

ETHNOPHARMACOLOGICAL RELEVANCE: Traditional Chinese medicines (TCMs) are often prepared in oral dosage forms, making TCMs interact with gut microbiota after oral administration, which could affect the therapeutic effect of TCM. Xiaoyao Pills (XYPs) are a commonly used TCM in China to treat depression. The biological underpinnings, however, are still in its infancy due to its complex chemical composition. AIM OF THE STUDY: The study aims to explore XYPs' underlying antidepressant mechanism from both in vivo and in vitro. MATERIALS AND METHODS: XYPs were composed of 8 herbs, including the root of Bupleurum chinense DC., the root of Angelica sinensis (Oliv.) Diels, the root of Paeonia lactiflora Pall., the sclerotia of Poria cocos (Schw.) Wolf, the rhizome of Glycyrrhiza uralensis Fisch., the leaves of Mentha haplocalyx Briq., the rhizome of Atractylis lancea var. chinensis (Bunge) Kitam., and the rhizome of Zingiber officinale Roscoe, in a ratio of 5:5:5:5:4:1:5:5. The chronic unpredictable mild stress (CUMS) rat models were established. After that, the sucrose preference test (SPT) was carried out to evaluate if the rats were depressed. After 28 days of treatment, the forced swimming test and SPT were carried out to evaluate the antidepressant efficacy of XYPs. The feces, brain and plasma were taken out for 16SrRNA gene sequencing analysis, untargeted metabolomics and gut microbiota transformation analysis. RESULTS: The results revealed multiple pathways affected by XYPs. Among them, the hydrolysis of fatty acids amide in brain decreased most significant via XYPs treatment. Moreover, the XYPs' metabolites which mainly derived from gut microbiota (benzoic acid, liquiritigenin, glycyrrhetinic acid and saikogenin D) were found in plasma and brain of CUMS rats and could inhibit the levels of FAAH in brain, which contributed to XYPs' antidepressant effect. CONCLUSIONS: The potential antidepressant mechanism of XYPs by untargeted metabolomics combined with gut microbiota-transformation analysis was revealed, which further support the theory of gut-brain axis and provide valuable evidence of the drug discovery.

Cost-effectiveness of ceftazidime/avibactam plus metronidazole versus meropenem as first-line empiric therapy for the treatment of complicated intra-abdominal infections: A study based on the in-vitro surveillance data in China.

BACKGROUND: With the increase in drug resistance rates of pathogens isolated from complicated intra-abdominal infections (cIAIs), ceftazidime/avibactam (CAZ-AVI) is increasingly used clinically. However, given the high drug cost and the fact that not yet covered by the health insurance payment, this study evaluated the cost-effectiveness of CAZ-AVI plus metronidazole versus meropenem as a first-line empiric treatment for cIAIs from the perspective of the Chinese healthcare system. METHODS: A decision analytic model with a one-year time horizon was constructed to assess the cost-effectiveness based on the entire disease course. Model inputs were mainly obtained from clinical studies, published literature, and publicly available databases. Primary outcomes were cost, quality-adjusted life years (QALYs), life years (Lys), and incremental cost-effectiveness ratio (ICER). One-way sensitivity analysis and probabilistic sensitivity analysis were also performed. RESULTS: In the base cases, compared to meropenem, CAZ-AVI plus metronidazole had a shorter mean hospital length of stay (-0.77 days per patient) and longer life expectancy (+0.05 LYs and +0.06 QALYs). CAZ-AVI plus metronidazole had an ICER of $25517/QALY, which is well below the threshold of $31509 per QALY in China. The one-way sensitivity analysis showed that the change of the treatment duration of CAZ-AVI plus metronidazole was the parameter that most influenced the results of the ICER. In probabilistic sensitivity analysis, CAZ-AVI plus metronidazole was the optimal strategy in 75% of simulations at $31510/QALY threshold. CONCLUSIONS: CAZ-AVI plus metronidazole could be considered as a cost-effective option for the empiric treatment of patients with cIAIs in China, and this benefit will be more evident when the price of CAZ-AVI decreases by 23.8%.

Risk Factors Affecting the Outcomes of CT-Guided Radiofrequency Thermocoagulation of Thoracic Sympathetic Nerve in the Treatment of Primary Palm Hyperhidrosis.

BACKGROUND: Primary palm hyperhidrosis (PPH) is a chronic disease characterized by uncontrolled palm-sweating exceeding physiological needs. It negatively impacts the quality of life of the patients and can lead to different degrees of psychological problems. Currently, there are a variety of treatment options for PPH, of which thoracotomy is a first-line treatment that has shown good efficacy. However, since it is an invasive procedure requiring general anesthesia and is often associated with high costs and serious complications, better alternatives should be explored. Computed tomography (CT)-guided percutaneous puncture of radiofrequency thermocoagulation (RF-TC) of the thoracic sympathetic nerve is a promising alternative treatment. It is a minimally invasive procedure that can be performed under local anesthesia and is associated with rapid recovery. However, the factors affecting the duration of the surgery-related benefits and outcomes of CT-guided percutaneous RF-TC of the thoracic sympathetic nerve are unclear. OBJECTIVES: To investigate the factors influencing the outcomes of CT-guided percutaneous RF-TC of the thoracic sympathetic nerve in patients with PPH. STUDY DESIGN: A retrospective study. SETTING: This study was conducted at the Pain Department of Jiaxing University Affiliated Hospital (Jiaxing, China). METHODS: After approval by the Ethics Committee of the Affiliated Hospital of Jiaxing College, the data of 232 corresponding patients were assessed. The Kaplan-Meier method was used for survival analysis. Univariate and multivariate analyses were performed to identify factors associated with PPH and to construct a nomogram for predicting postoperative recurrence. Time-independent receiver operating characteristic (ROC) curve analyses were performed to assess the nomogram's predictive capacity. RESULTS: In the one-year survival analysis model, gender (HR = 1.573, 95%CI: 0.844 to 2.934), age (HR = 0.965, 95%CI: 0.915 to 1.018), disease course (HR = 0.960, 95%CI: 0.908 to 1.015), palm temperature difference (HR = 0.377, 95%CI: 0.287 to 0.495), perfusion index difference (HR = 0.590, 95%CI: 0.513 to 0.680) and hyperhidrosis disease severity scale (HR = 1.963, 95%CI: 0.769 to 5.011) were identified as statistically significant factors in univariate analysis, while palm temperature difference (HR = 0.589, 95%CI: 0.369 to 0.941) and perfusion index difference (HR = 0.357, 95%CI: 0.588 to 0.968) were the independent factors in the multivariate Cox proportional hazards risk model. In the 2-year survival analysis model, palm temperature difference (HR = 0.353, 95%CI: 0.261 to 0.478), perfusion index difference (HR = 0.589, 95%CI: 0.510 to 0.680) and hyperhidrosis disease severity scale (HR = 1.964, 95%CI: 0.771 to 5.006) were the statistically significant factors while palm temperature difference (HR = 0.507, 95%CI: 0.321 to 0.799) and perfusion index difference (HR = 0.789, 95%CI: 0.625 to 0.995) were the independent factors. LIMITATIONS: This single-center retrospective study was limited by its small sample size, short follow-up time, and the possibility of bias resulting from the non-random patient selection. CONCLUSION: Palm temperature difference and perfusion index difference were independent risk factors associated with prolonging the surgical benefits and reducing postoperative recurrence of CT-guided RF-TC of the sympathetic nerves in patients with PPH.

Exploring the Relationship between Allergic Rhinitis and Constitution Based on the "Traditional Chinese Medicine Constitution Theory".

Allergic rhinitis (AR) is a prevalent allergic disease affecting individuals of all ages, especially children and adolescents. Patients with AR develop a specific immunoglobulin E antibody response to allergens, including pollen, mold, dust mites, and animal dander. The main symptoms of AR patients include nasal congestion, rhinorrhea, sneezing, and nasal itching. Symptoms such as these can interfere with the patient's sleep and quality of life when they become severe. Moreover, AR contributes too many complications, can exacerbate asthma, and has a negative impact on productivity and social costs. Therefore, the current review focuses on how to treat AR effectively. This review discusses the correlation between AR and constitution from the perspective of the Traditional Chinese Medicine (TCM) Constitution Theory in light of increasing research on AR in TCM. The constitution is adjustable, and adjusting the patient's biased constitution can improve the diagnosis, treatment, and prognosis of the disease. TCM constitution is critical in AR pathogenesis, and both are closely linked. TCM constitution theory can be applied to treat AR with positive effects, which merits popularization and application, and provides a new approach to the treatment of AR.

Pyrolysis of vegetable oil soapstock in fluidized bed: Characteristics of thermal decomposition and analysis of pyrolysis products.

This study investigated the effect of temperature on pyrolysis of soapstock in a fluidized bed reactor, and the characterization of soapstock chars (SCs) and pyrolysis oils (POs) were analyzed. TGA, TG-FTIR, TG-MS, and Py-GCMS were employed to investigate characteristics of SS pyrolysis. Experimental results indicated that the yield of SC decreased with increasing temperature. Pyrolysis oil (PO) yield reached the maximum of 21.05 wt% at 600 °C and the yield of non-condensable gas varied with temperatures. The content of carbon, hydrogen and nitrogen distributed in the SC decreased with the increasing temperature, and sulfur tended to be retained in SC during pyrolysis with the distribution ratio of 0.55-0.62. Ketones, alcohols and hydrocarbons were the dominate substances in PO, and higher temperature promoted the production of short-chain alkanes and the conversion of alkenes to benzene derivatives. SS pyrolysis can be divided into three stages. Stage I was mainly the evaporation of free water and light organics in the raw material. Decomposition and conversion of organics mainly occurred at stage II. Stage III was the decomposition of CaCO3 and secondary cracking of residual organics. Ca2+ delayed the pyrolysis reaction of fatty acids and promoted decarboxylation which was the main deoxygenation pathway, and alkene production. This study provided a theoretical basis for the application of soapstock thermochemical treatment. It is of great significance for the quality improvement of PO and pollution control for pyrolysis processes.

Electroacupuncture Attenuates Cancer-Induced Bone Pain via NF-κB/CXCL12 Signaling in Midbrain Periaqueductal Gray.

Electroacupuncture (EA) is effective in various chronic pains. NF-κB and CXCL12 modulate the formation of chronic pain. Herein, we hypothesized that EA alleviates cancer-induced bone pain (CIBP) through NF-κB/CXCL12 axis in midbrain periaqueductal gray (PAG), which participates in "top-down" pain modulatory circuits. In order to filter the optimum EA frequency for CIBP treatment, 2, 100, or 2/100 Hz EA was set up. In addition, ipsilateral, contralateral, and bilateral EA groups were established to affirm the optimal EA scheme. Bilateral 2/100 Hz EA was considered as the optimal therapeutic scheme and was applied in a subsequent experiment. Western blotting along with immunofluorescence illustrated that CIBP induces a rapid and substantial increase in CXCL12 protein level and NF-κB phosphorylation in vlPAG from day 6 to day 12. Anti-CXCL12 neutralizing antibody and pAAV-U6-shRNA(CXCL12)-CMV-EGFP-WPRE in vlPAG remarkably improved the mechanical pain threshold of the hind paw in CIBP model relative to the control. EA inhibited the upregulation of pNF-κB and CXCL12 in vlPAG of CIBP. The recombinant CXCL12 and pAAV-CMV-CXCL12-EF1a-EGFP-3Xflag-WPRE reversed the abirritation of EA in the CIBP rat model. NF-κB phosphorylation mediated-CXCL12 expression contributed to CIBP allodynia, whereas EA suppressed NF-κB phosphorylation in CIBP. According to the above evidence, we conclude that bilateral 2/100 Hz EA is an optimal therapeutic scheme for CIBP. The abirritation mechanism of EA might reduce the expression of CXCL12 by inhibiting the activation of NF-κB, which might lead to the restraint of descending facilitation of CIBP.

Petroleum oil and products recovery from oily sludge: Characterization and analysis of pyrolysis products.

Oily sludge (OS) has attracted special interest because of its hazardous nature and high potential as an energy resource. This study investigated the oil recovery from OS by thermal cracking and catalytic pyrolysis. The oil yield increased when the temperature exceeded 450 °C and reached a maximum (76.84 wt%) at 750 °C. Catalysts significantly improved the quality of oil produced during catalytic pyrolysis. Aromatic hydrocarbons were dominant (10.01-52.69%) in pyrolysis oil (PO) from OS catalytic pyrolysis, and the catalysts significantly reduced the presence of oxygen heterocycles. In addition, KOH and CaO reduced the ID (D-band peak intensity)/IG (G-band peak intensity) of OS char (OC) and increased the degree of graphitization. Owing to its higher iodine adsorption value and methylene blue (MB) adsorption value, OC exhibits potential as an adsorbent. The environmental assessment and potential applications of OC, along with possible reaction mechanisms and kinetic characteristics, are also discussed.

Influences of petroleum hydrocarbon pyrene on the formation, stability and antibacterial activity of natural Au nanoparticles.

The effect of pyrene on the formation of naturally Au nanoparticles (AuNPs) in the presence of humic acid (HA) under UV irradiation is described. TEM, EDS, FTIR and XPS were carried out to prove the formation of AuNPs and display their morphologies and formation mechanism. There are little differences between size, morphology and function groups of surface coated materials of AuNPs formed with and without pyrene. With the presence of HA, pyrene showed an inhibiting effect on the reduction of Au ion via competition for O2•-, thereby decreasing the production of AuNPs. However, AuNPs formed by HA-pyrene showed higher stability than AuNPs formed by HA with the sedimentation rates of 4.13% and 13.68% respectively after 30-d standing. As for the antibacterial activities against Staphylococcus aureus and Escherichia coli, AuNPs formed by HA-pyrene were more toxic than AuNPs formed by HA. Meanwhile, changes of environmental factors such as temperature, pH and ionic strength exhibited similar influence trend on the formation of AuNPs in the presence and absence of pyrene. The results suggest that the typical petroleum hydrocarbon pyrene contained in spilled oil could influence the formation, fate and ecotoxicity of AuNPs.

Large-scale phenotypic drug screen identifies neuroprotectants in zebrafish and mouse models of retinitis pigmentosa.

Retinitis pigmentosa (RP) and associated inherited retinal diseases (IRDs) are caused by rod photoreceptor degeneration, necessitating therapeutics promoting rod photoreceptor survival. To address this, we tested compounds for neuroprotective effects in multiple zebrafish and mouse RP models, reasoning drugs effective across species and/or independent of disease mutation may translate better clinically. We first performed a large-scale phenotypic drug screen for compounds promoting rod cell survival in a larval zebrafish model of inducible RP. We tested 2934 compounds, mostly human-approved drugs, across six concentrations, resulting in 113 compounds being identified as hits. Secondary tests of 42 high-priority hits confirmed eleven lead candidates. Leads were then evaluated in a series of mouse RP models in an effort to identify compounds effective across species and RP models, that is, potential pan-disease therapeutics. Nine of 11 leads exhibited neuroprotective effects in mouse primary photoreceptor cultures, and three promoted photoreceptor survival in mouse rd1 retinal explants. Both shared and complementary mechanisms of action were implicated across leads. Shared target tests implicated parp1-dependent cell death in our zebrafish RP model. Complementation tests revealed enhanced and additive/synergistic neuroprotective effects of paired drug combinations in mouse photoreceptor cultures and zebrafish, respectively. These results highlight the value of cross-species/multi-model phenotypic drug discovery and suggest combinatorial drug therapies may provide enhanced therapeutic benefits for RP patients.

Photoreceptors are the cells responsible for vision. They are part of the retina: the light-sensing tissue at the back of the eye. They come in two types: rods and cones. Rods specialise in night vision, while cones specialise in daytime colour vision. The death of these cells can cause a disease, called retinitis pigmentosa, that leads to vision loss. Symptoms often start in childhood with a gradual loss of night vision. Later on, loss of cone photoreceptors can lead to total blindness. Unfortunately, there are no treatments available that protect photoreceptor cells from dying. Research has identified drugs that can protect photoreceptors in animal models, but these drugs have failed in humans. The classic way to look for new treatments is to find drugs that target molecules implicated in a disease, and then test them to see if they are effective. Unfortunately, many drugs identified in this way fail in later stages of testing, either because they are ineffective, or because they have unacceptable side effects. One way to reverse this trend is to first test whether a drug is effective at curing a disease in animals, and later determining what it does at a molecular level. This could reveal whether drugs can protect photoreceptors before research to discover their molecular targets begins. Tests like this across different species could maximise the chances of finding a drug that works in humans, because if a drug works in several species, it is more likely to have shared target molecules across species. Applying this reasoning, Zhang et al. tested around 3,000 drug candidates for treating retinitis pigmentosa in a strain of zebrafish that undergoes photoreceptor degeneration similar to the human disease. Most of these drug candidates already have approval for use in humans, meaning that if they were found to be effective for treating retinitis pigmentosa, they could be fast-tracked for use in people. Zhang et al. found three compounds that helped photoreceptors survive both in zebrafish and in retinas grown in the laboratory derived from a mouse strain with degeneration similar to retinitis pigmentosa. Tests to find out how these three compounds worked at the molecular level revealed that they interfered with a protein that can trigger cell death. The tests also found other promising compounds, many of which offered increased protection when combined in pairs. Worldwide there are between 1.5 and 2.5 million people with retinitis pigmentosa. With this disease, loss of vision happens slowly, so identifying drugs that could slow or stop the process could help many people. These results suggest that placing animal testing earlier in the drug discovery process could complement traditional target-based methods. The compounds identified here, and the information about how they work, could expand potential treatment research. The next step in this research is to test whether the drugs identified by Zhang et al. protect mammals other than mice from the degeneration seen in retinitis pigmentosa.

Clostridium Butyricum ZJU-F1 Benefits the Intestinal Barrier Function and Immune Response Associated with Its Modulation of Gut Microbiota in Weaned Piglets.

This study investigated the effects of dietary C. butyricum ZJU-F1 on the apparent digestibility of nutrients, intestinal barrier function, immune response, and microflora of weaned piglets, with the aim of providing a theoretical basis for the application of Clostridium butyricum as an alternative to antibiotics in weaned piglets. A total of 120 weanling piglets were randomly divided into four treatment groups, in which piglets were fed a basal diet supplemented with antibiotics (CON), Bacillus licheniformis (BL), Clostridium butyricum ZJU-F1 (CB), or Clostridium butyricum and Bacillus licheniformis (CB-BL), respectively. The results showed that CB and CB-BL treatment increased the intestinal digestibility of nutrients, decreased intestinal permeability, and increased intestinal tight junction protein and mucin expression, thus maintaining the integrity of the intestinal epithelial barrier. CB and CB-BL, as exogenous probiotics, were also found to stimulate the immune response of weaned piglets and improve the expression of antimicrobial peptides in the ileum. In addition, dietary CB and CB-BL increased the proportion of Lactobacillus. The levels of butyric acid, propionic acid, acetic acid, and total acid were significantly increased in the ceca of piglets fed CB and CB-BL. Furthermore, we validated the effects of C. butyricum ZJU-F1 on the intestinal barrier function and immune response in vitro and found C. butyricum ZJU-F1 improved intestinal function and enhanced the TLR-2-MyD88-NF-κB signaling.

Overall assessment of antibiotic substitutes for pigs: a set of meta-analyses.

BACKGROUND: Antibiotic growth promoters are widely used to improve weight gain. However, the abuse of antibiotics can have many negative effects on people. Developing alternatives to antibiotics is an urgent need in livestock production. We aimed to perform a meta-analysis and network meta-analysis (NMA) to investigate the effects of feed additives as potential antibiotic substitutes (ASs) on bacteriostasis, growth performance, intestinal morphology and immunity. Furthermore, the primary, secondary, and tertiary ASs were defined by comparing their results with the results of antibiotics. RESULTS: Among 16,309 identified studies, 37 were summarized to study the bacteriostasis effects of feed additives, and 89 were included in the meta-analysis and NMA (10,228 pigs). We summarized 268 associations of 57 interventions with 32 bacteria. The order of bacteriostasis effects was as follows: antimicrobial peptides (AMPs) ≈ antibiotics>organic acids>plant extracts>oligosaccharides. We detected associations of 11 feed additives and 11 outcomes. Compared with a basal diet, plant extract, AMPs, probiotics, microelements, organic acids, bacteriophages, lysozyme, zymin, and oligosaccharides significantly improved growth performance (P < 0.05); organic acids, probiotics, microelements, lysozyme, and AMPs remarkably increased the villus height:crypt depth ratio (V/C) (P < 0.05); and plant extracts, zymin, microelements, probiotics, and organic acids notably improved immunity (P < 0.05). The optimal AMP, bacteriophage, lysozyme, microelements, oligosaccharides, organic acids, plants, plant extracts, probiotics, and zymin doses were 0.100%, 0.150%, 0.012%, 0.010%, 0.050%, 0.750%, 0.20%, 0.040%, 0.180%, and 0.100%, respectively. Compared with antibiotics, all investigated feed additives exhibited no significant difference in effects on growth performance, IgG, and diarrhoea index/rate (P > 0.05); AMPs and microelements significantly increased V/C (P < 0.05); and zymin significantly improved lymphocyte levels (P < 0.05). Furthermore, linear weighting sum models were used to comprehensively estimate the overall impact of each feed additive on pig growth and health. CONCLUSIONS: Our findings suggest that AMPs and plant extracts can be used as primary ASs for weaned piglets and growing pigs, respectively. Bacteriophages, zymin, plants, probiotics, oligosaccharides, lysozyme, and microelements can be regarded as secondary ASs. Nucleotides and organic acids can be considered as tertiary ASs. Future studies should further assess the alternative effects of combinational feed additives.

Atractylodis macrocephalae polysaccharides protect against DSS-induced intestinal injury through a novel lncRNA ITSN1-OT1.

Many dietary polysaccharides have been shown to protect the intestinal barrier integrity against several noxious stimuli. Previously, we have isolated a polysaccharide RAMPtp from Atractylodis macrocephalae Koidz, and analyzed its structure. However, the effects of RAMPtp on intestinal barrier function have not been investigated. Here, we evaluated the protective effects of RAMPtp on Dextran sulfate sodium (DSS)-induced intestinal epithelial cells (IECs) injury. The findings showed that RAMPtp boosted the proliferation and survival of IECs during DSS stimulation. Furthermore, we found that RAMPtp protected the IECs from injury induced by DSS through maintaining the barrier function and inflammation response. Mechanistically, we identified a novel lncRNA ITSN1-OT1, which was induced by RAMPtp during DSS stimulation. It blocked the nuclear import of phosphorylated STAT2 to prevent the DSS induced decreased expression and structural destroy of tight junction proteins. Hence, the study clarified the protective effects and mechanism of polysaccharides RAMPtp on DSS-induced intestinal barrier dysfunction.

Animal-Derived and Plant-Derived Protein Supplement Feeds Are Important Sources of Organophosphate Esters in the Food Supply.

Animal protein supplement feeds (APFs) are important raw feed materials for livestock. APFs might be susceptible to organophosphate esters (OPEs) but have not been paid attention yet. In the present study, animal-derived (meat meal, feather meal, and blood meal) and plant-derived APFs were all found to contain detectable levels of OPEs, with 16 target OPEs ranging from 12.6 ng/g dry weight (dw) to 301 ng/g dw. Meat meal contained the highest OPE level (mean: 117 ± 75.6 ng/g dw), followed by feather meal (54.6 ± 30.0 ng/g dw), plant-derived feed (41.9 ± 16.0 ng/g dw), and blood meal (28.0 ± 12.0 ng/g dw). Considering its widespread consumption, plant-derived APFs might be an important source of OPE exposure for livestock. Dust adhesion contributed to OPE contamination both in feather meal and plant-derived APFs. Congener patterns varied among the different APFs. Tris(2-chloroisopropyl) phosphate dominated in the plant-derived feed and blood meal, while tris(2-chloroethyl) phosphate and triphenyl phosphate were the major contributors in meat meal and feather meal, respectively. Tributyl phosphate and tri-iso-butyl phosphate were found to be statistically correlated in all APFs (p < 0.01), indicating their similar behavior and common sources. The protein-associated transport pathways of OPEs need to be studied separately for different protein matrices in the future.

Heterogeneous Non-noble Catalyst for Highly Selective Production of Linear α-Olefins from Fatty Acids: A Discovery of NiFe/C.

Catalytic deoxygenation of even-numbered fatty acids into odd-chain linear α-olefins (LAOs) has emerged as a complementary strategy to oligomerization of ethylene, which only affords even-chain LAOs. Although enzymes and homogeneous catalysts have shown promising potential for this application, industrial production of LAOs through these catalytic systems is still very difficult to accomplish to date. A recent breakthrough involves the use of an expensive noble-metal catalyst, Pd/C, through a phosphine ligands-assisted method for LAOs production from fatty acid conversion. This study presents a unique, cost-friendly, non-noble bimetallic NiFe/C catalyst for highly selective LAOs production from fatty acids through decarbonylative dehydration. In the presence of acetic anhydride and phosphine ligand, a remarkable improvement in the yield of 1-heptadecene from the conversion of stearic acid was found over the supported bimetallic catalyst (NiFe/C) as compared to corresponding monometallic counterparts (Ni/C and Fe/C). Through optimization of the reaction conditions, a 70.1 % heptadecene yield with selectivity to 1-heptadecene as high as 92.8 % could be achieved over the bimetallic catalyst at just 190 °C. This unique bimetallic NiFe/C catalyst is composed of NiFe alloy in the material bulk phase and a surface mixture of NiFe alloy and oxidized NiFeδ+ species, which offer a synergized contribution towards decarbonylative dehydration of stearic acid for 1-heptadecene production.

Camellia oil (Camellia oleifera Abel.) attenuates CCl4-induced liver fibrosis via suppressing hepatocyte apoptosis in mice.

Liver fibrosis is a common part of the pathological development of many chronic liver diseases. As liver fibrosis progresses, it may lead to cirrhosis, portal hypertension, liver decompensation, liver tumours, and death. Camellia oil (Camellia oleifera Abel.) is widely used as an edible oil in China. It has a wide range of biological activities and is used as a traditional medicine to treat conditions such as burns and stomach pains. However, whether camellia oil can ameliorate liver fibrosis remains unclear. We constructed a liver fibrosis model induced by carbon tetrachloride (CCl4) and then confirmed the role of camellia oil in liver fibrosis by biochemical examination, histopathological morphology, immunohistochemistry, and western blot analysis. We found that camellia oil ameliorated histopathological lesions, improved liver function and antioxidant capacity, decreased the expression of TGF-ß1 and α-SMA proteins, and downregulated the expression of the pro-apoptotic proteins in CCl4-induced liver fibrosis. Therefore, these results suggest that camellia oil attenuates CCl4-induced liver fibrosis in mice, and its mechanism may function via reduction of hepatocyte apoptosis to inhibit hepatic stellate cell (HSC) activation. Camellia oil may provide a potential new treatment for liver fibrosis as an auxiliary treatment by addition of the edible oil to the daily diet.