Palmatine ameliorated lipopolysaccharide-induced sepsis-associated encephalopathy mice by regulating the microbiota-gut-brain axis.

BACKGROUND: Sepsis-associated encephalopathy (SAE), a common neurological complication from sepsis, is widespread among patients in intensive care unit and is linked to substantial morbidity and mortality rates, thus posing a substantial menace to human health. Due to the intricate nature of SAE's pathogenesis, there remains a dearth of efficacious therapeutic protocols, encompassing pharmaceutical agents and treatment modalities, up until the present time. Palmatine exhibits distinctive benefits in the regulation of inflammation for the improvement of sepsis. Nevertheless, the precise functions of palmatine in treating SAE and its underlying mechanism have yet to be elucidated. PURPOSE: This study aimed to evaluate efficiency of palmatine in SAE mice and its underlying mechanisms. STUDY DESIGN AND METHODS: Behavioral experiments, percent survival rate analysis, histological analysis, immunofluorescence staining, ELISA analysis, were performed to evaluate the efficiency of palmatine in SAE mice. Quantibody® mouse inflammation array glass chip was performed to observe the effects of palmatine on inflammation storm in SAE mice. Real-time quantitative and western blotting analyzes were employed to examine the expression of relevant targets in the Notch1/nuclear factor-kappa B (NF-κB) pathway. Finally, brain tissues metabolomics-based analyzes were performed to detect the differentially expressed metabolites and metabolic pathways. The fecal samples were subjected to microbial 16S rRNA analysis and untargeted metabolomics analysis in order to identify the specific flora and metabolites associated with SAE, thereby further investigating the mechanism of palmatine in SAE mice. RESULTS: Our results showed that palmatine significantly improved nerve function, reduced cell apoptosis in brain tissue, and decreased inflammatory cytokine levels in SAE induced-LPS mice. Meanwhile, our results demonstrate the potential of palmatine in modulating key components of the Notch1/NF-κB pathway, enhancing the expression of tight junction proteins, improving intestinal permeability, promoting the growth of beneficial bacteria (such as Lachnospiraceae_NK4A136_group), inhibiting the proliferation of harmful bacteria (such as Escherichia-Shigella), and mitigating metabolic disorders. Ultimately, these observed effects contribute to the therapeutic efficacy of palmatine in treating SAE. CONCLUSION: The findings of our study have provided confirmation regarding the efficacy of palmatine in the treatment of SAE, thereby establishing a solid foundation for further exploration into SAE therapy and the advancement and investigation of palmatine.

Apocynum venetum leaf extract alleviated doxorubicin-induced cardiotoxicity by regulating organic acid metabolism in gut microbiota.

Apocynum venetum leaf is commonly utilized for its beneficial effects in reducing blood pressure, inducing sedation, promoting diuresis, anti-aging, and cardioprotection, which also exhibit positive effects on the gut microbiota. The gut microbiota plays a role as an endocrine organ by producing bioactive metabolites that can directly or indirectly impact host physiology, specifically cardiovascular diseases. In this study, main chemical components of A. venetum leaf extract (AVLE) were identified by LC-MS, and an orally administered AVLE was employed to treat mice with doxorubicin (Dox)-induced cardiotoxicity. The results showed that AVLE contained hyperoside and oganic acids. The pharmacological findings revealed that AVLE regulated the gut microbiota, resulting in a significant increase in the levels of two organic acids, indole-3-propionic acid (IPA) and acetic acid (AA). Both IPA and AA exhibited the ability to reduce BNP, CK, and LDH levels in mice with Dox-induced cardiotoxicity. Moreover, IPA demonstrated an improvement in Dox-induced cardiac injury by inhibiting apoptosis, while AA promoted increased secretion of ghrelin through the parasympathetic nervous system, subsequently reducing cardiac fibrosis by decreasing collagen I, collagen III, and activin A. Hence, our study demonstrates that AVLE exerts a beneficial cardioprotective effect by modulating the gut microbiota, providing a potential novel target for the treatment and prevention of Dox-induced cardiotoxicity.

UMI-77 Modulates the Complement Cascade Pathway and Inhibits Inflammatory Factor Storm in Sepsis Based on TMT Proteomics and Inflammation Array Glass Chip.

Sepsis is a systemic inflammatory response syndrome caused by infection, which has no specific drug at present. UMI-77 can significantly improve the survival rate of septic mice; the detailed role of UMI-77 and its underlying mechanisms in sepsis are not clear. Inflammation array glass chip and proteomic analyses were performed to elucidate the latent mechanism of UMI-77 in the treatment of sepsis. The results showed that 7.0 mg/kg UMI-77 improved the 5 day survival rate in septic mice compared to the LPS group (60.964 vs 9.779%) and ameliorated the pathological conditions. Inflammation array glass chip analysis showed that sepsis treatment with UMI-77 may eventually through the suppression of the characteristic inflammatory storm-related cytokines such as KC, RANTES, LIX, IL-6, eotaxin, TARC, IL-1ß, and so on. Proteomics analysis showed that 213 differential expression proteins and complement and coagulation cascades were significantly associated with the process for the UMI-77 treatment of sepsis. The top 10 proteins including Apoa2, Tgfb1, Serpinc1, Vtn, Apoa4, Cat, Hp, Serpinf2, Fgb, and Serpine1 were identified and verified, which play important roles in the mechanism of UMI-77 in the treatment of sepsis. Our findings indicate that UMI-77 exerts an antisepsis effect by modulating the complement cascade pathway and inhibiting inflammatory storm factors.

Design, Synthesis, and Biological Evaluation of Novel Derivatives of the Marine Natural Product Laurene.

Plant pathogenic fungi and viruses are seriously threatening agricultural production. There is an urgent need to develop novel fungicides and antiviral agents with low toxicity and high efficiency. In this study, we designed and synthesized 32 thiazole-, hydrazone-, and amide-containing derivatives of laurene and systematically evaluated their antiviral activities and fungicidal activities. Structure-simplified compounds 5a-5c, 5i, 5k, 5l, 11a, 11j, and 12c displayed higher antiviral activities than that of ningnanmycin. Compound 11a with a simple chemical structure, convenient synthetic route, and excellent antiviral activity emerged as a secondary lead compound. The docking results show that compounds 5i, 5k, and 11a have strong interactions with the tobacco mosaic virus coat protein (TMV CP). These compounds also exhibited significant fungicidal activities. Compounds 5g, 5k, 11j, and 11l displayed 9.15-17.45 µg/mL EC50 values against Pyricularia grisea, and compounds 5h (EC50: 8.01 µg/mL) and 11i (EC50: 15.23 µg/mL) exhibited a similar level of EC50 values with chlorothalonil (EC50: 7.33 µg/mL) against Physalospora piricola. Preliminary fungicidal mechanism research indicated that compound 5h has a certain destructive effect on the hyphae of P. piricola. This work lays a foundation for the application of laurene derivatives in plant protection.

Phenylpropanoid amides from Solanum rostratum and their phytotoxic activities against Arabidopsis thaliana.

Introduction: Solanum rostratum, an annual malignant weed, has seriously damaged the ecological environment and biodiversity of invasion area. This alien plant gains a competitive advantage by producing some new phytotoxic substances to inhibit the growth of native plants, thus achieving successful invasion. However, the chemical structures, inhibitory functions and action mechanisms of phytotoxic substances of S. rostratum remain unclear. Methods: In this study, to clarify the chemical structures of phytotoxic substances from S. rostratum, we isolated phenylpropanoid amides from the plant. Their structures were identified by comprehensive HR-ESIMS, NMR and ECD data. And the inhibitory functions of isolated phenylpropanoid amides on one model plant (Arabidopsis thaliana) were also investigated. In addition, the action mechanisms of active phenylpropanoid amides were revealed by antioxidant-related enzymes [Catalase (CAT), Peroxidase (POD), Superoxide dismutase (SOD)] activities and corresponding molecular docking analyses. Results and Discussion: Phytochemical research on the whole plant of S. rostratum led to the isolation and identification of four new phenylpropanoid amides (1-4), together with two known analogues (5-6). All the compounds showed phytotoxic effects with varying levels on the seed germination and root elongation of one model plant (Arabidopsis thaliana), especially compound 2 and 4. Likewise, compounds 2 and 4 displayed potent inhibitory effects on antioxidant-related enzyme (POD). In addition, compounds 2 and 4 formed common conventional hydrogen bonds with residues Ala34 and Ser35 in POD revealed by molecular docking analyses. These findings not only helped to reveal the invasion mechanism of S. rostratum from the perspective of "novel weapons hypothesis", but also opened up new ways for the exploitation and utilization of S. rostratum.

[Mechanism of gypenoside XVII against cerebral ischemia/reperfusion injury based on nuclear factor erythroid 2-related factor 2/antioxidant responsive element signaling pathway].

OBJECTIVE: To explore the mechanism of gypenoside XVII against cerebral ischemia/reperfusion (I/R) through nuclear factor erythroid 2-related factor 2/antioxidant responsive element (Nrf2/ARE) signaling pathway. METHODS: Forty SPF Sprague Dawley (SD) rats were randomly divided into sham operated group, I/R model group, 25, 50 and 100 mg/kg gypenoside XVII groups (n = 8). Gypenoside XVII groups were administered 25, 50 or 100 mg/kg (0.01 mL/g) gypenoside XVII by intragastric administration for 14 days; the other two groups received the same dose of saline. Rat cerebral I/R model was established by modified line bolt method; rats in the sham operated group underwent the same procedure without producing substantial embolization. After 24 hours of reperfusion, the neurological deficit scores of the rats in each group were assessed. Rat abdominal aortic whole blood was collected and the serum reactive oxygen species (ROS), heme oxygenase-1 (HO-1), γ-glutamylcysteine synthase (γ-GCS), superoxide dismutase (SOD), quinone NADH oxidoreductase 1 (NQO1), and malondialdehyde (MDA) were detected. Then whole brain tissue was harvested and penumbra tissue was isolated from cerebral cortex, the general condition of rat brain tissue and the volume of cerebral infarction were evaluated, the histopathological changes in the brain were observed under light microscopy, the mRNA expressions of Nrf2 and Keap1 were measured by real-time fluorescent quantitative polymerase chain reaction (RT-qPCR), the protein expressions of Nrf2 and Keap1 were determined by Western blotting. RESULTS: After 24 hours of reperfusion, compared with the sham operated group, the score of neurological deficit and infarct volume were significantly increased, the NQO1, SOD and γ-GCS levels in serum were significantly decreased, MDA, HO-1 and ROS levels in serum were significantly increased, the Nrf2 and Keap1 mRNA and protein expressions in the ischemic penumbra were significantly increased in rats from I/R model group. Compared with the I/R model group, the neurological deficit scores (1.50±0.53, 1.37±0.52 vs. 2.75±0.46) and brain infarct volume [(19.8±5.1)%, (21.4±6.4)% vs. (42.3±5.8)%] were significantly reduced, serum NQO1, SOD, HO-1 and γ-GCS were significantly increased [NQO1 (ng/L): 186.05±10.38, 220.75±16.22 vs. 131.36±5.95, SOD (kU/L): 63.23±5.30, 72.70±8.62 vs. 36.75±6.55, HO-1 (ng/L): 60.57±7.93, 60.35±4.72 vs. 42.72±4.95, γ-GCS (kU/L): 8.81±0.53, 8.72±0.69 vs. 6.80±0.56], serum MDA and ROS levels were significantly reduced [MDA (µmol/L): 5.94±0.66, 5.61±0.53 vs. 10.88±1.34, ROS (kU/L): 69.11±4.23, 67.12±4.52 vs. 104.43±7.54], the mRNA and protein expressions of Nrf2 and Keap1 in the ischemic penumbra were significantly increased in rats from 50 mg/kg and 100 mg/kg gypenoside XVII groups [Nrf2 mRNA (2-ΔΔCt): 1.90±0.13, 2.13±0.18 vs. 1.48±0.11, Keap1 mRNA (2-ΔΔCt): 1.78±0.11, 1.85±0.10 vs. 1.43±0.10, Nrf2/ß-actin: 0.73±0.04, 0.79±0.03 vs. 0.60±0.03, Keap1/ß-actin: 0.71±0.01, 0.76±0.03 vs. 0.61±0.01], all the comparative differences were statistically significant (all P < 0.01); 25 mg/kg gypenoside XVII had no significant effect. CONCLUSIONS: Gypenoside XVII (50 mg/kg and 100 mg/kg) may play a role in anti-cerebral I/R injury by regulating NQO1, SOD, HO-1, γ-GCS, ROS and MDA through Nrf2/ARE signaling pathway.

VGLL4-TEAD1 promotes vascular smooth muscle cell differentiation from human pluripotent stem cells via TET2.

The Hippo signaling pathway plays a critical role in cardiovascular development and stem cell differentiation. Using microarray profiling, we found that the Hippo pathway components vestigial-like family member 4 (VGLL4) and TEA domain transcription factor 1 (TEAD1) were upregulated during vascular smooth muscle cell (VSMC) differentiation from H1 ESCs (H1 embryonic stem cells). To further explore the role and molecular mechanisms of VGLL4 in regulating VSMC differentiation, we generated a VGLL4-knockdown H1 ESC line (heterozygous knockout) using the CRISPR/Cas9 system and found that VGLL4 knockdown inhibited VSMC specification. In contrast, overexpression of VGLL4 using the PiggyBac transposon system facilitated VSMC differentiation. We confirmed that this effect was mediated via TEAD1 and VGLL4 interaction. In addition, bioinformatics analysis revealed that Ten-eleven-translocation 2 (TET2), a DNA dioxygenase, is a target of TEAD1, and a luciferase assay further verified that TET2 is the target of the VGLL4-TEAD1 complex. Indeed, TET2 overexpression promoted VSMC marker gene expression and countered the VGLL4 knockdown-mediated inhibitory effects on VSMC differentiation. In summary, we revealed a novel role of VGLL4 in promoting VSMC differentiation from hESCs and identified TET2 as a new target of the VGLL4-TEAD1 complex, which may demethylate VSMC marker genes and facilitate VSMC differentiation. This study provides new insights into the VGLL4-TEAD1-TET2 axis in VSMC differentiation and vascular development.

Exploring the Latent Mechanism of Huanglian Jiedu Decoction Formula for Anti-atopic Dermatitis by Systems Pharmacology.

BACKGROUND: Atopic dermatitis (AD) is a chronic inflammatory skin disease, which does not have a specific drug presently. Huanglian jiedu decoction (HJD) is one of the effective traditional Chinese medicine prescriptions. The real material and mechanisms of HJD for AD are not clear. OBJECTIVE: Network pharmacology and in vivo experiments were used to explore the real material and mechanisms of HJD for AD. METHODS: A systems' pharmacology approach that provides a comprehensive analysis of bioactive compounds, targets, and pathway interactions was employed to elucidate the molecular pathogenesis of HJD for AD. First, the compound databases were constructed for HJD, and compound targets were predicted. Then, the hub targets of HJD were selected by degree centrality analysis and validated using the molecular docking method. Finally, Compound-Target and Target-Pathway networks were constructed to explore the latent mechanism of HJD for AD. Then, animal models of AD were established, the pathology of the skin lesions was observed, and RT-PCR and ELISA methods were used to verify the key targets in the serum of AD mice. RESULTS: The results showed that 60 bioactive compounds (palmatine, wogonin, cavidine, etc.) of HJD interacting with 169 related hub targets (PTGS2, HSP90AA1, etc.) were authenticated. HJD potentially participates in response to stimuli, biological regulation, and reproduction through the PI3K-Akt signaling pathway, MAPK signaling pathway, Ras signaling pathway, and Fc epsilon RI signaling pathway, which are interrelated to the pathogenesis of AD. Compared with the control group, the thickening of the epidermis in the model group was obvious with inflammatory cells infiltrating, the levels of PI3K, AKT, JNK, ERK, IL-4 and TNF-α were up-regulated; and 6.4g/kg and 12.8g/kg HJD could significantly reduce the thickening of the epidermis and infiltration of inflammatory cells, down-regulate the levels of PI3K, AKT, JNK, ERK, IL-4 and TNF-α in the AD mice. HJD might exert its anti-AD effects by downregulating key indicators (PI3K, AKT, JNK, ERK, IL-4, and TNF-α) in the PI3K/AKT and MAPK pathways. CONCLUSIONS: Our study could help us understand the compound and mechanism of HJD for AD. Moreover, it had a guidance function to change the traditional arrangement of formula for HJD.

[Textual research on Bambusae Concretio Silicea].

By studying various ancient texts such as herbal classics and medical literature from different eras, it was found that there were discrepancies in the records about Bambusae Concretio Silicea(Tian Zhu Huang). In order to establish an accurate foundation, this research was based on ancient herbal literature and combined with plant morphology and investigative studies to examine its earliest mentions in ancient texts, nomenclature, medicinal properties, indications, and quality assessment standards. In the early records, Bambusae Concretio Silicea was referred to by several different names, such as "Zhu Huang" "Tian Zhu Huang" "Zhu Gao" "Zhu Tang", and "Zhu Huang". The earliest known formal usage of the name "Tian Zhu Huang" was found in the book Ri Hua-zi's Materia Medica(Ri Hua Zi Ben Cao). Throughout various ancient texts, the earliest recorded information about Bambusae Concretio Silicea also appeared in Ri Hua-zi's Materia Medica, not in Materia Medica of Sichuan(Shu Ben Cao) or other ancient texts. Ri Hua-zi's Materia Medica provided relevant descriptions of its origin, medicinal properties, and indications, albeit with some errors due to limited knowledge. However, this has been a valuable starting point for future research on Bambusae Concretio Silicea and holds pioneering significance in forming a mature system. As the research delved deeper, the medicinal properties of Bambusae Concretio Silicea have been consistent since Ri Hua-zi's Materia Medica, and the understanding has gradually improved through years of clinical verification. During the investigation process, the authors found limited records on the quality evaluation of Bambusae Concretio Silicea in ancient texts. Although the information is scarce, it serves as a foundational basis for establishing corresponding quality grading standards for Bambusae Concretio Silicea in the future.

Cornus officinalis prior and post-processing: Regulatory effects on intestinal flora of diabetic nephropathy rats.

Background: Diabetic nephropathy (DN) is one of the most common and serious chronic complications in the clinic. Cornus officinalis has the effects of replenishing qi and nourishing yin, tonifying liver and kidney, and it is one of the main traditional Chinese medicines used clinically to treat diabetes and its complications. However, the effect and mechanism of Cornus officinalis before and after processing on intestinal flora of diabetic nephropathy need to be further elucidated. Methods: SD rats were randomly divided into a blank group (10 rats) and DN groups (70 rats). After 4 weeks of high-sugar and high-fat diet, the DN rat model was established by intraperitoneal injection of streptozotocin. After successful modeling, the rats were randomly divided into DN model group, irbesartan group (1.35 mg·kg-1), Cornus officinalis group (281.25 mg·kg-1), wine Cornus officinalis group (281.25 mg·kg-1), wine honey Cornus officinalis group (281.25 mg·kg-1), auxiliary wine group (10 ml·kg-1), auxiliary wine honey group (10 ml·kg-1). During the observation of the rats' general state, after 6 weeks of continuous administration, the fasting blood glucose of rats in each group was detected, and the kidney index was calculated. The serum creatinine levels, urea nitrogen and 24 h urinary microalbumin were detected by enzyme-linked immunosorbent assay. The expression levels of YKL-40, Wnt4, ß-catenin and TGF-ß 1 mRNA in renal tissue were detected by fluorescence quantitative PCR. Hematoxylin-eosin staining was used to observe the changes in renal pathological injury in each group; GC-MS detected the changes of short chain fatty acid content. Feces were collected for 16 s high-throughput sequencing to analyze the effects of Cornus officinalis on the diversity of intestinal flora in DN before and after processing. Results: Compared with the blank group, the serum creatinine, urea nitrogen, 24 h urinary microalbumin, kidney index and fasting blood glucose in the DN model group were significantly increased (p < 0.05). The renal tissue morphology was disordered and a large number of inflammatory cells were infiltrated. The expression of YKL-40, Wnt4, ß-catenin and TGF-ß 1 mRNA was significantly increased (p < 0.05). Compared with the DN model group, the serum creatinine, urea. Nitrogen, 24 h urine microalbumin, kidney index and fasting blood glucose of rats in each administration group were significantly decreased (p < 0.05), and the general condition and pathological renal damage of DN rats were improved. The effect of wine honey Cornus officinalis was the best, and the expression of YKL-40, Wnt4, ß-catenin and TGF-ß 1 mRNA was significantly decreased (p < 0.05). In each administration group, the improvement of the above indicators in the wine honey Cornus officinalis group was significantly better than that in the raw Cornus officinalis group and wine Cornus officinalis group (p < 0.05), There was no significant difference compared with the irbesartan group (p > 0.05). Each administration group had a significant callback effect on the content of short-chain fatty acids in rat feces, with increased intestinal beneficial bacteria and decreased pathogenic bacteria. Compared with the blank group, the abundance of Firmicutes in the DN model group increased, the abundance of Bacteroidetes decreased, and the ratio showed an upward trend in the DN model group decreased. Each administration group could improve the relative abundance of the above intestinal flora in the model group to varying degrees. Conclusion: The processing of Cornus officinalis may improve the renal injury of DN rats by blocking the activation of Wnt/ß-catenin signaling pathway, regulating the structural composition of intestinal microorganisms, and ultimately playing a role in renal protection.

Niloticin binds to MD-2 to promote anti-inflammatory pathway activation in macrophage cells.

OBJECTIVES: Niloticin is an active compound isolated from Cortex phellodendri with uncharacterized anti-inflammatory activity. We assessed the drug potential of niloticin and examined its ability to target myeloid differentiation protein 2 (MD-2) to ascertain the mechanism for its anti-inflammatory activity. METHODS: The Traditional Chinese Medicine Systems Pharmacology Database was used to evaluate niloticin. Bio-layer interferometry and molecular docking technologies were used to explore how niloticin targets MD-2, which mediates a series of toll-like receptor 4 (TLR4)-dependent inflammatory responses. The cytokines involved in the lipopolysaccharide (LPS)-TLR4/MD-2-NF-κB pathway were evaluated using ELISA, RT-qPCR, and western blotting. RESULTS: Niloticin could bind to MD-2 and had no evident effects on cell viability. Niloticin treatment significantly decreased the levels of NO, IL-6, TNF-α, and IL-1ß induced by LPS (p < 0.01). IL-1ß, IL-6, iNOS, TNF-α, and COX-2 mRNA expression levels were decreased by niloticin (all p < 0.01). Compared with that in the control group, the increase in TLR4, p65, MyD88, p-p65, and iNOS expression levels induced by LPS were suppressed by niloticin (all p < 0.01). CONCLUSION: Our results suggest that niloticin has therapeutic potential and binds to MD-2. Niloticin binding to MD-2 antagonized the effects of LPS binding to the TLR4/MD-2 complex, resulting in the inhibition of the LPS-TLR4/MD-2-NF-κB signaling pathway.

The interaction of MD-2 with small molecules in huanglian jiedu decoction play a critical role in the treatment of sepsis.

Huanglian Jiedu Decoction (HJD) is used for treating sepsis in China. Active components from HJD refer to various active ingredients of HJD, while active component formulation (ACF) refers to the combination of palmatine, berberine, baicalin, and geniposide from HJD according to the quantity of HJD. The detailed mechanisms of the active components from HJD and ACF in sepsis treatment are unclear. Molecular docking, surface plasmon resonance (SPR), ELISA, RT-qPCR, and Western blotting were used to assay the possible mechanism in vitro. The efficacy and mechanism of ACF and HJD were assessed by pharmacodynamics and metabolomics analyses, respectively. The results revealed that palmatine, berberine, baicalin, and geniposide showed good binding capacity to MD-2; decreased the release of NO, TNF-α, IL-6, and IL-1ß; inhibited the mRNA expression of iNOS, TNF-α, IL-6, IL-1ß, and COX-2; and downregulated the protein expressions of MD-2, MyD88, p-p65, and iNOS induced by LPS; which indicated that they can inactivate the LPS-TLR4/MD-2-NF-κB pathway. Thus, ACF was formed, and the pharmacodynamics assay suggested that ACF can reduce inflammatory cell infiltration and organ damage in accordance with HJD. Furthermore, 39 metabolites were selected and identified and the regulatory effect of these metabolites by ACF and HJD was almost consistent, but ACF might alleviate physical damage caused by HJD through regulating metabolites, such as 3-hydroxyanthranilic acid. ACF could represent HJD as a new formulation to treat sepsis.

Expert consensus statement on therapeutic drug monitoring and individualization of linezolid.

Linezolid is an oxazolidinone antibacterial drug, and its therapeutic drug monitoring and individualized treatment have been challenged since its approval. With the in-depth clinical research of linezolid, we have changed our attitude toward its therapeutic drug monitoring and our view of individualized treatment. On the basis of summarizing the existing clinical studies, and based on the practical experience of each expert in their respective professional fields, we have formed this expert consensus. Our team of specialists is a multidisciplinary team that includes pharmacotherapists, clinical pharmacology specialists, critical care medicine specialists, respiratory specialists, infectious disease specialists, emergency medicine specialists and more. We are committed to the safe and effective use of linezolid in patients in need, and the promotion of its therapeutic drug monitoring.

[Study on discovery of efficacy markers for Dachaihu Decoction and its action mechanism].

Dachaihu Decoction is a classical Chinese herbal prescription that is effective in harmonizing lesser yang and purging internal accumulated heat. At present, it has been widely used in clinical practice, and the resulting outcomes are satisfactory. However, its quality indicators and action mechanism are still not clear. Therefore, this paper explored the efficacy markers of Dachaihu Decoction and its action mechanism based on literature mining, molecular biology, and network pharmacology, so as to better control its quality and ensure its clinical efficacy. The efficacy markers of Dachaihu Decoction were predicted and analyzed according to the "five principles" for Q-markers of Chinese herbs. Then the anti-inflammatory activity of the efficacy markers of Dachaihu Decoction was evaluated with Griess reagent after the establishment of RAW264.7 cell inflammation model in vitro with lipopolysaccharide(LPS). The potential targets of efficacy markers were predicted by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP), ChEMBL, and SwissTargetPrediction, followed by the construction of the protein-protein interaction(PPI) network of the efficacy markers of Dachaihu Decoction. Topological, GO, and KEGG enrichment analysis was carried out to construct the "key target-signaling pathway-biological process" network, thus elucidating the action mechanism of the efficacy markers of Dachaihu Decoction. Saikosaponin B_2, baicalin, baicalein, wogonoside, neohesperidin, naringin, hesperidin, and paeoniflorin were considered as the potential efficacy markers of Dachaihu Decoction. The anti-inflammatory activity evaluation showed that the potential efficacy markers effectively inhibited the release of NO, exhibiting good anti-inflammatory activities. As demonstrated by network pharmacology, the efficacy markers of Dachaihu Decoction regulated the inflammatory response by acting on MAPK and NF-κB signaling pathways, the carbohydrate metabolism by HIF-1 and PI3 K-AKT signaling pathways, and the lipid metabolism by AMPK and PI3 K-AKT signaling pathways. This study discovered the efficacy markers of Dachaihu Decoction based on literature mining combined with molecular biological experiments and explored its action mechanism at the molecular level based on network pharmacology, which would provide reference for the quality control of Dachaihu Decoction and scientific basis for its clinical application.

Marine Sesquiterpenes for Plant Protection: Discovery of Laurene Sesquiterpenes and Their Derivatives as Novel Antiviral and Antiphytopathogenic Fungal Agents.

The unreasonable use or long-term use of a single variety of pesticide has led to drug resistance and made the pesticides ineffective. Therefore, the creation of new, efficient, and low-risk pesticides is imminent. Marine natural products play a vital role in serving as new lead compounds. In this work, we realized the efficient preparation of nine marine sesquiterpenes with the Stork-Danheiser reaction as the key step and designed and synthesized a series of their derivatives. The antiviral activity and antifungal activity research showed that these compounds exhibited good to excellent biological activities. Compounds 7b and 8e displayed significantly higher antiviral activities against tobacco mosaic virus (TMV) than ribavirin and could be used as new antiviral candidates. The antiviral mode of action research indicated that compound 8e inhibited the formation of the 20S protein disk by acting on the TMV coat protein and therefore inhibited the assembly of TMV particles. This work provides a new idea for the development of new pesticides based on marine sesquiterpenes.

Enhancing the bioactivity of hydroxyapatite bioceramic via encapsulating with silica-based bioactive glass sol.

Although hydroxyapatite (HA) bioceramic has excellent biocompatibility and osteoconductivity, its high chemical stability results in slow degradation which affects osteogenesis, angiogenesis and clinical applications. Silica-based bioglass (BG) with superior biological performance has been introduced into HA bioceramic to overcome this insufficiency; however, the composite bioceramics are usually prepared by traditional mechanical mixture of HA and BG powders, which tremendously weakens their mechanical performance. In this research, BG-modified HA bioceramics were prepared by the use of BG sol encapsulated HA powders. The results showed that introducing 1 and 3 wt% BG allowed the HA-based bioceramics to maintain the high compressive strength (>300 MPa), improved the apatite mineralization activity, and played an important role in cellular response. The bioceramic modified with 1 wt% BG (1BG/HA) remarkably enhanced in vitro cell proliferation, osteogenic and angiogenic activities. This present work provides a new strategy to improve the biological performance of bioceramics and the HA-based bioceramics with 1 wt% BG can be as a promising candidate material for bone repair.

The Anti-Inflammatory and Anti-Pruritus Mechanisms of Huanglian Jiedu Decoction in the Treatment of Atopic Dermatitis.

Atopic dermatitis (AD) is a common chronic skin disease driven by a T-cell-mediated immune response, with inflammation and pruritus being its main clinical manifestations. Huanglian Jiedu decoction (HLJDT), which is an ancient Chinese medicine herbal formula derived from Wai-Tai-Mi-Yao, is a potentially effective treatment for AD. We aimed to clarify the anti-inflammatory and anti-pruritus mechanisms of HLJDT in AD treatment. We performed immunohistochemistry, Western blotting, reverse transcriptase-polymerase chain reaction, Luminex-based direct multiplex immunoassay, enzyme-linked immunosorbent assays, and flow cytometry to address the abovementioned aims. HLJDT significantly reduced clinical symptoms and ear swelling in AD-like mice by inhibiting the production of cytokines [histamine, interleukin (IL)-3, IL-4, IL-5, IL-13, IL-17A, IL-31, and IL-33], substance P (SP), transient receptor potential cation channel subfamily V member 1 (TRPV-1), and gastrin-releasing peptide (GRP). Additionally, HLJDT significantly suppressed the protein expression levels and positive cell percentage of CD28, CD80, CD86, CD207, CD326, MHCII, and OX40 in the lymphoid nodes. Moreover, HLJDT significantly suppressed mRNA and protein expression of tyrosine-protein kinase (JAK1), histamine H4 receptor, and IL-4Rα, as well as the protein expression of GRP, SP, and TRPV-1 in the root ganglion. Our findings indicate that HLJDT can treat AD by regulating the antigen presentation function of dendritic cells, weakening T-lymphocyte activation, and subsequently exerting anti-inflammatory and anti-pruritus effects.

Study on the Molecular Basis of Huanglian Jiedu Decoction Against Atopic Dermatitis Integrating Chemistry, Biochemistry, and Metabolomics Strategies.

Atopic dermatitis (AD) is a common chronic relapsing skin inflammation, which severely affect the quality of life of patients. Inhibiting itching and enhancing immunity to mitigate scratching are key elements in the fight against AD. Huanglian Jiedu decoction (HLJDD) has multiple pharmacological effects in the treatment of AD. However, the effective ingredients and underlying molecular mechanisms have not yet been fully explored. Thus, this study integrates chemistry, biochemistry, and metabolomics strategies to evaluate the active substance basis of HLJDD against AD. First, HLJDD was split to five fractions (CPF, 40AEF, 90AEF, PEF and WEF) and 72 chemical components were identified. NSD (Non-similarity degree) among the different fractions showed significant chemical differences (>81%). Interleukin IL-13, IL-17A, IL-3, IL-31, IL-33, IL4, IL-5, TSLP, IgE, and histamine in the serum, and IL-4Rα, JAK1, and HRH4 levels in skin, participating in inhibiting itching and regulating immunity signaling, were found to be restored to varying degrees in AD treating with HLJDD and its fractions, especially 40AEF and CPF. Untargeted metabolomics analysis demonstrated that forty metabolites were differential metabolites in plasma between the HLJDD-treated group and the AD group, involving in histidine metabolism, arginine biosynthesis, pyrimidine metabolism, and so on. Further, targeted metabolomics analysis revealed that eleven differential metabolites, associating with physiological and biochemical indices, were significant improved in the HLJDD and its fractions groups. In conclusion, HLJDD exhibited anti-AD effects by inhibiting itching and enhancing immunity, which in turn regulating the levels of relative metabolites, and CPF and 40AEF were considered the most important components of HLJDD.

Determining procalcitonin at point-of-care; A method comparison study of four commercial PCT assays.

OBJECTIVE: Procalcitonin (PCT) testing adds value in the early detection of infection and sepsis, as well as in management of antibiotic therapy. We determined the analytical and diagnostic performance of four PCT assays at POC. METHODS: PCT assays on AQT90 FLEX, Getein 1100, mLabs, and Finecare POC analyzers, in whole blood and plasma, were analyzed for repeatability, linearity, accuracy and concordance, by comparing with our reference PCT assay on the Cobas E602 system. RESULTS: For all assays precision was found higher in plasma than in whole blood. AQT90 showed good performance in all analytical and diagnostic areas, irrespective of test matrix and PCT concentration. The other POC assays demonstrated at least one analytical weakness. The Getein assay showed adequate precision only in plasma at high PCT levels, the mLabs assay only in plasma at low PCT levels. Accuracy, as demonstrated by Bland-Altman and Passing-Bablok analysis, was found adequate only for the AQT90 FLEX and Getein 1100 assay. Diagnostic concordance at 0.5 â€‹ng/mL was found excellent for the AQT90 FLEX, Getein 1100, and Finecare assays, much lower for the mLabs assay. At 0.25 â€‹ng/mL, only the AQT90 FLEX and Finecare assays showed excellent concordance with the reference assay. CONCLUSIONS: The AQT90 FLEX PCT assay demonstrated excellent analytical performance and diagnostic agreement with the Cobas E602 assay, allowing both stand-alone and side-by-side testing. The other assays demonstrated some analytical deficiencies, potentially limiting their diagnostic use. Any clinical use of PCT results should always be in combination with all other clinical signs and diagnostic information.