Broad-spectrum hydrocarbon-degrading microbes in the global ocean metagenomes.

Understanding the diversity and functions of hydrocarbon-degrading microorganisms in marine environments is crucial for both advancing knowledge of biogeochemical processes and improving bioremediation methods. In this study, we leveraged nearly 20,000 metagenome-assembled genomes (MAGs), recovered from a wide array of marine samples across the global oceans, to map the diversity of aerobic hydrocarbon-degrading microorganisms. A broad bacterial diversity was uncovered, with a notable preference for degrading aliphatic hydrocarbons over aromatic ones, primarily within Proteobacteria and Actinobacteriota. Three types of broad-spectrum hydrocarbon-degrading bacteria were identified for their ability to degrade various hydrocarbons and possession of multiple copies of hydrocarbon biodegradation genes. These bacteria demonstrate extensive metabolic versatility, aiding their survival and adaptability in diverse environmental conditions. Evidence of gene duplication and horizontal gene transfer in these microbes suggested a potential enhancement in the diversity of hydrocarbon-degrading bacteria. Positive correlations were observed between the abundances of hydrocarbon-degrading genes and environmental parameters such as temperature (-5 to 35 °C) and salinity (20 to 42 PSU). Overall, our findings offer valuable insights into marine hydrocarbon-degrading microorganisms and suggest considerations for selecting microbial strains for oil pollution remediation.

GPR39 regulated spinal glycinergic inhibition and mechanical inflammatory pain.

G protein-coupled receptor 39 (GPR39) senses the change of extracellular divalent zinc ion and signals through multiple G proteins to a broad spectrum of downstream effectors. Here, we found that GPR39 was prevalent at inhibitory synapses of spinal cord somatostatin-positive (SOM+) interneurons, a mechanosensitive subpopulation that is critical for the conveyance of mechanical pain. GPR39 complexed specifically with inhibitory glycine receptors (GlyRs) and helped maintain glycinergic transmission in a manner independent of G protein signalings. Targeted knockdown of GPR39 in SOM+ interneurons reduced the glycinergic inhibition and facilitated the excitatory output from SOM+ interneurons to spinoparabrachial neurons that engaged superspinal neural circuits encoding both the sensory discriminative and affective motivational domains of pain experience. Our data showed that pharmacological activation of GPR39 or augmenting GPR39 interaction with GlyRs at the spinal level effectively alleviated the sensory and affective pain induced by complete Freund's adjuvant and implicated GPR39 as a promising therapeutic target for the treatment of inflammatory mechanical pain.

Deciphering resveratrol's role in modulating pathological pain: From molecular mechanisms to clinical relevance.

Pathological pain, a multifaceted and debilitating ailment originating from injury or post-injury inflammation of the somatosensory system, poses a global health challenge. Despite its ubiquity, reliable therapeutic strategies remain elusive. To solve this problem, resveratrol, a naturally occurring nonflavonoid polyphenol, has emerged as a potential beacon of hope owing to its anti-inflammatory, antioxidant, and immunomodulatory capabilities. These properties potentially position resveratrol as an efficacious candidate for the management of pathological pain. This concise review summaries current experimental and clinical findings to underscore the therapeutic potential of resveratrol in pathological pain, casting light on the complex underlying pathophysiology. Our exploration suggests that resveratrol may exert its analgesic effect by the modulating pivotal signaling pathways, including PI3K/Akt/mTOR, TNFR1/NF-κB, MAPKs, and Nrf2. Moreover, resveratrol appears to attenuate spinal microglia activation, regulate primary receptors in dorsal root sensory neurons, inhibit pertinent voltage-gated ion channels, and curb the expression of inflammatory mediators and oxidative stress responses. The objective of this review is to encapsulate the pharmacological activity of resveratrol, including its probable signaling pathways, pharmacokinetics, and toxicology pertinent to the treatment of pathological pain. Hopefully, we aim to map out promising trajectories for the development of resveratrol as a potential analgesic.

[Research progress in pharmacotherapy of insomnia].

Insomnia is extremely common and is a risk factor for a variety of physical and psychological disorders in addition to contributing to the reduced quality of life of patients and the burden of healthcare costs. Although cognitive behavioral therapy is the first-line treatment for insomnia, its difficulty of access and high cost have hindered its application. Therefore, pharmacotherapy remains the common treatment choice for patients and clinicians. Existing chemical drugs including benzodiazepine receptor agonists, dual orexin receptor antagonists, melatonin and its receptor agonists, histamine antagonists, antidepressants, and antipsychotics are able to induce and/or maintain sleep and have good therapeutic effects on acute insomnia, but their efficacy on chronic insomnia is indefinite. Furthermore, they have several side effects and affect sleep structure and physiological function. Under the guiding principle of holistic view and treatment based on syndrome differentiation, traditional Chinese medicine(TCM) has shown a good effect in clinical practice, but with little high-grade clinical evidence. The mechanism, dose, half-life period, adjustment of sleep structure, and side effects of hypnotic drugs are key factors to be considered for clinical use. This paper analyzed and summarized the drugs for insomnia from the above aspects, and is expected to provide references for the application and development of sedative and hypnotic drugs.

Acupoint compatibility effect: increasing "effect value" and expanding "effect domain". / è §ç©´é ä¼æ•ˆåº”.

By summarizing and exploring the theoretic connotation, key of functions and effect mechanism of acupoint compatibility, the effect of acupoint compatibility is concluded as the increase of "effect value" and the expansion of "effect domain". The increase of "effect value" is the concrete embodiment by the value of medical assessment scale, the value of objective index detection in clinical trial and the value of index detection in experiment research. The expansion of "effect domain" is the increase of effect target and the extension of effect scope. The paper interprets the scientific connotation of acupoint compatibility therapy from a new perspective, and emphasizes the innovative approaches to research while bringing forth new ideas on the research method. It is anticipated that a novel breakthrough can be achieved in the study of acupoint compatibility and the improvement of acupuncture-moxibustion efficacy.

Triterpenoid and Coumarin Isolated from Astilbe grandis with Anti-Inflammatory Effects through Inhibiting the NF-κB Pathway in LPS-Induced RAW264.7 Cells.

The roots of Astilbe grandis, known as "Ma sang gou bang", are used as a Miao traditional medicine with anti-inflammatory and analgesic properties. However, the active components and mechanism of action of this plant remain mostly uncharacterized. The aim of this study was to identify its active components and verify their pharmacological activity. The extract of A. grandis root was separated using various chromatographic methods. As a result, we obtained one novel triterpenoid, named astigranlactone (1), which has an unusual lactone moiety formed between C-7 and C-27. Additionally, a known coumarin compound, 11-O-galloyl bergenin (2) was isolated from this plant. The structures of these two compounds were elucidated by extensive NMR experiments in conjunction with HR-ESI-MS data. To the best of our knowledge, both compounds were isolated from this species for the first time. Moreover, we tested the anti-inflammation effect of the two compounds by establishing a cellular inflammation model induced by LPS in RAW264.7 cells. The effect of different concentrations of these compounds on the activity of RAW264.7 cells was assessed using a CCK8 assay. The levels of nitric oxide (NO), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1ß (IL-1ß) in the supernatant of each group were evaluated using the Griess method and an enzyme-linked immunosorbent assay (ELISA). Western blot and quantitative real-time PCR (qRT-RCR) were used to measure the levels of cyclooxygenase 2 (COX-2) and nitric oxide synthase (iNOS) gene expression. Our findings revealed that these two compounds inhibited the high levels of NO, TNF-α, IL-6, IL-1ß, COX-2, and iNOS (induced by LPS). Mechanistic studies demonstrated that these two compounds reduced the activation of the nuclear transcription factor-B (NF-κB) signaling pathway by inhibiting the phosphorylation of p65. Therefore, our study indicates that compounds 1 and 2 can exert a definite anti-inflammatory effect by inhibiting the NF-κB signaling pathway.

System pharmacology analysis to decipher the effect and mechanism of active ingredients combination from Duhuo Jisheng decoction on osteoarthritis in rats.

ETHNOPHARMACOLOGY RELEVANCE: Duhuo Jisheng decoction is a traditional Chinese formula that has been widely used in clinical practice to treat osteoarthritis, which has the effects of removing invaded cold and dampness, relieving joint pain. However, it is difficult to determine the effective substances and mechanisms due to assorted herbs and components, and further research is needed. AIM OF THE STUDY: This study was designed to explore and verify the mechanism and targets of DHJSD in the treatment of OA via network analysis and experiments. METHOD: In this study, the active ingredients of DHJSD were qualitatively analyzed by UPLC-QDA. Network analysis was used to identify common targets and pathways. Next, we explored the therapeutic mechanism of DHJSD through a rat model of knee osteoarthritis. HE staining was used to judge the establishment of the animal model. ELISA and Western blotting were used to verify the expression of key pathway proteins. CONCLUSION: In this study, seventeen chemical constituents in DHJSD were identified. According to the network analysis, we obtained the potential associated pathways of action. Then, molecular docking and SPR experiments showed that the sixteen identified components had high binding energies to IL-6. HE staining showed that the high-dose group of DHJSD had an obvious therapeutic effect on model rats. Compared with the model group, the levels of IL-1ß, TNF-α, IL-6, MMP3, MMP13, ADAMTS4 and ADAMTS5 in serum and the expression of STAT3 and p-STAT3 protein in administration groups were significantly decreased. This result indicated that the IL-6/STAT3 signaling pathway was one of the important pathways regulated by DHJSD to improve OA.

Salt processing: A unique and classic technology for Chinese medicine processing.

Traditional Chinese medicine (TCM) processing is the summary of long-term clinical experience, processing can change the property, taste and meridian of TCM, achieve the purpose of reducing toxicity and increasing efficiency, to ensure the safety of clinical medication. This paper summarizes the research advance of salt processing in recent years from the aspects of the types of excipients, salt processing methods, salt processing purpose and the influence of salt process on the chemical composition, pharmacodynamic effect and in vivo behavior of TCM, and analyzes and discusses the shortcomings of the current research, so as to provide ideas for the further research and development of salt processing of TCM. The literatures were classified and summarized by consulting the scientific database (such as SciFinder Scholar, CNKI, Google Scholar, Baidu Scholar, etc.), Chinese herbal classics and Chinese Pharmacopoeia and so on. The results show that salt processing is helpful to introduce drugs into the kidney channel and enhance the effect of nourishing Yin and falling fire. The pharmacological effect, chemical composition and in vivo behavior of TCM will change after salt processing. In the future, we should strengthen the research on standardizing the dosage of excipients, the quality standard after processing, the relationship between the change of chemical composition after salt processing and the enhancement of pharmacological efficacy, so as to deeply explain the principle of salt processing, and further improve and optimize the salt making process. By combing the influence of the of salt processing of TCM and analyzed the current problems, we hope to provide guidance for the in-depth study of the salt processing mechanism of TCM and the inheritance and innovation of TCM processing technology.

Anti-rheumatoid arthritis effects of Xanthii Fructus by affecting the PI3K-AKT signaling pathway based on TMT-labeled quantitative proteomics.

Rheumatoid arthritis is a systemic autoimmune disease characterized by chronic symmetrical multiple arthritis. Current traditional counter-therapies are expensive and have side effects. Xanthii Fructus has effects in expelling wind and cold, draining the nasal orifice, and removing wind and dampness. However, its mechanism of action against rheumatoid arthritis is unknown. In this paper, the mechanism of the anti- rheumatoid arthritis effect of Xanthii Fructus is studied by proteomics. The experimental results show that it could significantly reduce serum inflammatory factor levels, alleviate joint edema, improve vasodilation and congestion, and significantly reduce the number of inflammatory cells. Proteomics results show that the PI3K-AKT signaling pathway is the key pathway for Xanthii Fructus to treat rheumatoid arthritis. In this study, we obtained a new understanding of the mechanism of Xanthii Fructus in the treatment of rheumatoid arthritis, which provided a theoretical basis for its prevention and treatment and laid the foundation for further research.

Bioactive icetexane and abietane diterpenes from Isodon phyllopodus.

A new icetexane diterpenoid, 11, 12, 20α-trihydroxyl-7ß-methoxyicetexa-8, 11, 13-triene-19, 10-lactone [Phyllane A (1)], and a new abietane diterpenoid, 7ß, 20-epoxy-3ß, 17-acetoxy-abieta-8, 11, 13-teriene-11, 12-diol [phyllane B (2)], along with two known compounds (3 and 4) were isolated from the methanol (MeOH) extract of twigs and leaves of the folk medicinal Isodon phyllopodus. Their structures were determined by spectroscopic analyses including 2 D NMR spectral data, and further confirmed by X-ray single crystal diffraction. Moreover, the compounds were evaluated for their cytotoxicity and anti-HIV activities, and phyllane A showed anti-HIV activity with an IC50 value of 15.7 µM, but phyllane B was found to be cytotoxic to the A549 host cells with a CC50 value of 108.5 µM.

Role of potential bioactive metabolites from traditional Chinese medicine for type 2 diabetes mellitus: An overview.

Type 2 diabetes mellitus (T2DM) is a metabolic disease with persistent hyperglycemia primarily caused by insulin resistance (IR). The number of diabetic patients globally has been rising over the past decades. Although significant progress has been made in treating diabetes mellitus (DM), existing clinical drugs for diabetes can no longer fully meet patients when they face complex and huge clinical treatment needs. As a traditional and effective medical system, traditional Chinese medicine (TCM) has a unique understanding of diabetes treatment and has developed many classic and practical prescriptions targeting DM. With modern medicine and pharmacy advancements, researchers have discovered that various bioactive metabolites isolated from TCM show therapeutic on DM. Compared with existing clinical drugs, these bioactive metabolites demonstrate promising prospects for treating DM due to their excellent biocompatibility and fewer adverse reactions. Accordingly, these valuable metabolites have attracted the interest of researchers worldwide. Despite the abundance of research works and specialized-topic reviews published over the past years, there is a lack of updated and systematic reviews concerning this fast-growing field. Therefore, in this review, we summarized the bioactive metabolites derived from TCM with the potential treatment of T2DM by searching several authoritative databases such as PubMed, Web of Science, Wiley Online Library, and Springer Link. For the convenience of readers, the content is divided into four parts according to the structural characteristics of these valuable compounds (flavonoids, terpenoids, alkaloids, and others). Meanwhile, the detailed mechanism and future directions of these promising compounds curing DM are also summarized in the related sections. We hope this review inspires increasingly valuable and significant research focusing on potential bioactive metabolites from TCM to treat DM in the future.

Pharmacokinetic Comparison of Eight Major Compounds of Lonicerae japonicae flos after Oral Administration in Normal Rats and Rats with Liver Injury.

Traditional Chinese medicine considers Lonicerae japonicae flos to have antibacterial detoxification, liver protection, and gallbladder protection. At present, studies have proven that Lonicerae japonicae flos has a good therapeutic effect on liver injury. Therefore, to confirm the clinical applicability of Lonicerae japonicae flos in the treatment of liver injury, we were the first to compare the pharmacokinetics of an oral ethanol extract of Lonicerae japonicae flos in normal rats and carbon tetrachloride-induced liver injury model rats. A method was developed for the simultaneous determination of 3-caffeoylquinic acid, 4-caffeoylquinic acid, 5-caffeoylquinic acid, 3,5-dicaffeoylquinic acid, 4,5-dicaffeoylquinic acid, protocatechuic acid, Sweroside, and Secoxyloganin in rat plasma by ultra-performance liquid chromatography tandem mass spectrometry. The results show that the method is reliable and reproducible and can be used for quantitative determination of biological samples. The pharmacokinetic parameters showed that the area under the concentration-time curve of eight compounds in the model group was significantly increased. The results showed that the total absorption of the active components of Lonicerae japonicae flos in the blood increased, the clearance rate slowed down, and the bioavailability of Lonicerae japonicae flos increased in liver injury diseases.

Systematic review of Lonicerae Japonicae Flos: A significant food and traditional Chinese medicine.

Lonicerae Japonicae Flos has been used as a tea and medicine for more than 1,500 years. It has the functions of clearing heat, detoxification, and is often used to treat carbuncle, furuncle, throat arthralgia, erysipelas, heat-toxic blood dysentery, febrile fever. This paper summarizes the botany, ethnopharmacology, chemical composition and pharmacological action of Lonicerae Japonicae Flos from 1986 to 2022, and looks forward to the future research direction of Lonicerae Japonicae Flos. At present, the components isolated from Lonicerae Japonicae Flos include essential oils, organic acids, flavonoids, iridoids, saponins and other compounds. It has the effects of anti-inflammation, anti-virus, anti-bacteria, anti-oxidation, anti-tumor, protect liver and galltesticles, hypotensive, hypolipidemic, anti-thrombosis, anti-allergy, immune regulation and so on. It is often used in clinical treatment of diarrhea, hematochezia, febrile disease, exogenous wind-heat, and cold, swelling and toxin of carbuncle, sore throat and so on. The comprehensive evaluation of the quality of Lonicerae Japonicae Flos and the understanding of multi-target network pharmacology also need to be studied. As a kind of health food with high value, LJF is worthy of further promotion and development.

Efficacy and Safety of Gegen Qinlian Decoction for Pediatric Diarrhea: A Systematic Review and Meta-Analysis.

Objective: To evaluate the clinical efficacy and safety of Gegen Qinlian decoction in the treatment of pediatric diarrhea. Methods: A search for relevant RCTs was performed from which a systematic review and meta-analysis was conducted. This meta-analysis was registered at INPLASY (reference number ID: INPLASY202180105). Results: (1) Eleven trials involving 1126 patients were included in the meta-analysis. (2) Two trials recorded the adverse events. (3) The meta-analysis showed that compared with the control group, the experimental group has a significantly shorter duration of diarrhea in children (MD = -18.64, 95% CI (-23.76, -13.52), P < 0.00001), duration of fever (MD = -19.43, 95% CI (-25.76, -13.11), P < 0.00001), duration of vomiting [MD = -22.51, 95% CI (-29.92, -15.09), P < 0.00001], duration of correcting dehydration (MD = -23.35, 95% CI (-35.48, -11.22), P=0.0002), and the effective rate (OR = 4.64, 95% CI (3.12, 6.90), P < 0.00001). Conclusion: There were significant differences in the clinical efficacy in the treatment of pediatric diarrhea between the experimental and control groups. Thus, Gegen Qinlian decoction may have certain advantages in the treatment of pediatric diarrhea. In addition, we conclude the following: (1) the application of Gegen Qinlian decoction to treat this disease is recommended for >5 days. (2) We recommend conducting multicenter RCTs to avoid the impact of regional differences on the results. (3) We recommend using the unmodified Gegen Qinlian decoction, which may have better efficacy.

First Discovery of Beta-Sitosterol as a Novel Antiviral Agent against White Spot Syndrome Virus.

The outbreak of white spot syndrome (WSS) is a looming challenge, due to dramatic losses to the crustacean aquaculture industry. However, at present, there are no prophylactic or therapeutic means to control this infectious viral disease. Here, we screened fifteen medicinal plants for their inhibitory activity on the white spot syndrome virus (WSSV), using red swamp crayfish (Procambarus clarkii) as a model species. The results showed that the crude extracts of Pinellia ternata (Thunb.) Breit. had the highest inhibitory effect (91.59%, 100 mg/kg) on WSSV proliferation, and its main component, beta-sitosterol, showed a much higher activity (95.79%, 50 mg/kg). Further, beta-sitosterol potently reduced (p < 0.01) viral loads and viral gene transcription levels in a concentration-dependent fashion, and significantly promoted the survival rate of WSSV-challenged crayfish (57.14%, 50 mg/kg). The co-incubation assay indicated that beta-sitosterol did not influence the infectivity of WSSV particles. Both pre- and post-treatment of beta-sitosterol exerted a significant inhibitory effect (p < 0.01) on the viral load in vivo. Mechanistically, beta-sitosterol not only interfered with the expression of viral genes (immediate early gene 1, ie1; DNA polymerase, DNApol) that are important in initiating WSSV transcription, but it also attenuated the hijacking of innate immune signaling pathways (Toll, IMD, and JAK/STAT pathways) by viral genes to block WSSV replication. Moreover, the expression of several antiviral immune, antioxidant, pro-inflammatory, and apoptosis-related genes changed significantly in beta-sitosterol-treated crayfish. Beta-sitosterol is a potent WSSV inhibitor and has the potential to be developed as an effective anti-WSSV agent against a WSS outbreak in crustacean aquaculture.

Comparison of Pharmacokinetic Profiles of 14 Major Bioactive Components in Normal and Arthritic Model Rats after Oral Administration of Angelicae pubescentis Radix by UPLC-MS/MS.

An ultraperformance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method was established to simultaneously determine 14 compounds of Angelicae pubescentis Radix (APR) in normal and arthritis rat plasma in which chloramphenicol and daidzein were used as the internal standards. After protein precipitation with acetonitrile, separation was carried out on a Thermo Hypersil GOLD C18 column using gradient elution with 0.1% formic acid aqueous and acetonitrile consisting as the mobile phase at a flowing rate of 0.3 mL/min. A Thermo TSQ QUANTIS triple quadrupole mass spectrometer was used to detect 14 compounds in positive/negative ion exchange mode and this study was the first to investigate the pharmacokinetic changes of the active compounds in rats under the pathological state of arthritis. The method was verified and the results showed that the intra- and interday precision, accuracy, matrix effect, and extraction recovery were all acceptable, and the analytes were stable under different storage conditions. In addition, the pharmacokinetic behaviors of the 14 compounds were significantly different in model rats compared with normal rats. This indicated that the pharmacokinetic behavior of drugs will vary with the pathological state of the body, which suggested that individualized and reasonable drug administration plans should be formulated for different pathological states in clinical practice. This study provided a scientific basis and data support for better understanding the pharmacodynamic substance basis and clinical application of APR against arthritis.

Integrated spatially resolved metabolomics and network toxicology to investigate the hepatotoxicity mechanisms of component D of Polygonum multiflorum Thunb.

ETHNOPHARMACOLOGICAL RELEVANCE: The liver toxicity of Reynoutria multiflora (Thunb.) Moldenke. (Polygonaceae) (Polygonum multiflorum Thunb, PM) has always attracted much attention, but the related toxicity materials and mechanisms have not been elucidated due to multi-component and multi-target characteristics. In previous hepatotoxicity screening, different components of PM were first evaluated and the hepatotoxicity of component D [95% ethanol (EtOH) elution] in a 70% EtOH extract of PM (PM-D) showed the highest hepatotoxicity. Furthermore, the main components of PM-D were identified and their hepatotoxicity was evaluated based on a zebrafish embryo model. However, the hepatotoxicity mechanism of PM-D is unknown. AIM OF THE STUDY: This work is to explore the hepatotoxicity mechanisms of PM-D by integrating network toxicology and spatially resolved metabolomics strategy. MATERIALS AND METHODS: A hepatotoxicity interaction network of PM-D was constructed based on toxicity target prediction for eight key toxic ingredients and a hepatotoxicity target collection. Then the key signaling pathways were enriched, and molecular docking verification was implemented to evaluate the ability of toxic ingredients to bind to the core targets. The pathological changes of liver tissues and serum biochemical assays of mice were used to evaluate the liver injury effect of mice with oral administration of PM-D. Furthermore, spatially resolved metabolomics was used to visualize significant differences in metabolic profiles in mice after drug administration, to screen hepatotoxicity-related biomarkers and analyze metabolic pathways. RESULTS: The contents of four key toxic compounds in PM-D were detected. Network toxicology identified 30 potential targets of liver toxicity of PM-D. GO and KEGG enrichment analyses indicated that the hepatotoxicity of PM-D involved multiple biological activities, including cellular response to endogenous stimulus, organonitrogen compound metabolic process, regulation of the apoptotic process, regulation of kinase, regulation of reactive oxygen species metabolic process and signaling pathways including PI3K-Akt, AMPK, MAPK, mTOR, Ras and HIF-1. The molecular docking confirmed the high binding activity of 8 key toxic ingredients with 10 core targets, including mTOR, PIK3CA, AKT1, and EGFR. The high distribution of metabolites of PM-D in the liver of administrated mice was recognized by mass spectrometry imaging. Spatially resolved metabolomics results revealed significant changes in metabolic profiles after PM-D administration, and metabolites such as taurine, taurocholic acid, adenosine, and acyl-carnitines were associated with PM-D-induced liver injury. Enrichment analyses of metabolic pathways revealed tht linolenic acid and linoleic acid metabolism, carnitine synthesis, oxidation of branched-chain fatty acids, and six other metabolic pathways were significantly changed. Comprehensive analysis revealed that the hepatotoxicity caused by PM-D was closely related to cholestasis, mitochondrial damage, oxidative stress and energy metabolism, and lipid metabolism disorders. CONCLUSIONS: In this study, the hepatotoxicity mechanisms of PM-D were comprehensively identified through an integrated spatially resolved metabolomics and network toxicology strategy, providing a theoretical foundation for the toxicity mechanisms of PM and its safe clinical application.

Association of Gestational Vitamin E Status With Pre-eclampsia: A Retrospective, Multicenter Cohort Study.

Introduction: Pre-eclampsia is the second leading cause of maternal mortality worldwide. The controversy for the association of vitamin E with pre-eclampsia has raged unabated for two decades. We aimed to determine the association of vitamin E level in the first trimester and the gestational change with pre-eclampsia. Materials and Methods: A retrospective cohort study was conducted among singleton pregnant women aged 15-49 years at 137 hospitals in China. Serum vitamin E concentrations in the first trimester and at pre-eclampsia assessment time were uniformly quantified in a laboratory by high performance liquid chromatography. Logistic regression models with restricted cubic splines were performed to reveal a non-linear association of vitamin E concentrations in the first trimester and the gestational change with pre-eclampsia. Results: We included 73 317 participants (47.8% aged 25-29 years) and 2.28% were diagnosed with pre-eclampsia. Higher risk was observed in those with lower concentration in the first trimester and greater gestational decrease, with a range from 0.81 to 80.60%. A non-linear L-shaped association was observed between vitamin E concentrations in the first trimester and pre-eclampsia, suggesting a threshold at 7.3 mg/L and a ceiling effect: the risk saw a steep rise when the concentrations in the first trimester were < 7.3 mg/L but was relatively flat beyond the inflection point. Sharply increased pre-eclampsia risk was also found in those with gestational vitamin E decrease after accounting for the baseline status in the first trimester. However, gestational vitamin E increase was associated with decreased pre-eclampsia risk when the baseline concentrations were < 7.3 mg/L but did not confer additional benefits when it was above the threshold. Conclusion: We demonstrated alarmingly high pre-eclampsia risk in women with vitamin E concentrations of < 7.3 mg/L in the first trimester and gestational vitamin E decrease. These findings underscore the need to supplement vitamin E among pregnant women with low baseline status.

Screening and evaluating honokiol from Magnolia officinalis against Nocardia seriolae infection in largemouth bass (Micropterus Salmoides).

Nocardiosis caused by Nocardia seriolae is a major threat to the aquaculture industry. Given that prolonged therapy administration can lead to a growth of antibiotic resistant strains, new antibacterial agents and alternative strategies are urgently needed. In this study, 80 medicinal plants were selected for antibacterial screening to obtain potent bioactive compounds against N. seriolae infection. The methanolic extracts of Magnolia officinalis exhibited the strongest antibacterial activity against N. seriolae with the minimal inhibitory concentration (MIC) of 12.5 µg/ml. Honokiol and magnolol as the main bioactive components of M. officinalis showed higher activity with the MIC value of 3.12 and 6.25 µg/ml, respectively. Sequentially, the evaluation of antibacterial activity of honokiol in vivo showed that honokiol had good biosafety, and could significantly reduce the bacterial load of nocardia-infected largemouth bass (p < .001). Furthermore, the survival rate of nocardia-infected fish fed with 100 mg/kg honokiol was obviously improved (p < .05). Collectively, these results suggest that medicinal plants represent a promising reservoir for discovering active components against Nocardia, and honokiol has great potential to be developed as therapeutic agents to control nocardiosis in aquaculture.

Role of Licochalcone A in Potential Pharmacological Therapy: A Review.

Licochalcone A (LA), a useful and valuable flavonoid, is isolated from Glycyrrhiza uralensis Fisch. ex DC. and widely used clinically in traditional Chinese medicine. We systematically updated the latest information on the pharmacology of LA over the past decade from several authoritative internet databases, including Web of Science, Elsevier, Europe PMC, Wiley Online Library, and PubMed. A combination of keywords containing "Licochalcone A," "Flavonoid," and "Pharmacological Therapy" was used to help ensure a comprehensive review. Collected information demonstrates a wide range of pharmacological properties for LA, including anticancer, anti-inflammatory, antioxidant, antibacterial, anti-parasitic, bone protection, blood glucose and lipid regulation, neuroprotection, and skin protection. LA activity is mediated through several signaling pathways, such as PI3K/Akt/mTOR, P53, NF-κB, and P38. Caspase-3 apoptosis, MAPK inflammatory, and Nrf2 oxidative stress signaling pathways are also involved with multiple therapeutic targets, such as TNF-α, VEGF, Fas, FasL, PI3K, AKT, and caspases. Recent studies mainly focus on the anticancer properties of LA, which suggests that the pharmacology of other aspects of LA will need additional study. At the end of this review, current challenges and future research directions on LA are discussed. This review is divided into three parts based on the pharmacological effects of LA for the convenience of readers. We anticipate that this review will inspire further research.