Gut microbiota in insulin resistance: a bibliometric analysis.

Background: Insulin resistance (IR) is considered the pathogenic driver of diabetes, and can lead to obesity, hypertension, coronary artery disease, metabolic syndrome, and other metabolic disorders. Accumulating evidence indicates that the connection between gut microbiota and IR. This bibliometric analysis aimed to summarize the knowledge structure of gut microbiota in IR. Methods: Articles and reviews related to gut microbiota in IR from 2013 to 2022 were retrieved from the Web of Science Core Collection (WoSCC), and the bibliometric analysis and visualization were performed by Microsoft Excel, Origin, R package (bibliometrix), Citespace, and VOSviewer. Results: A total of 4 749 publications from WoSCC were retrieved, including 3 050 articles and 1 699 reviews. The majority of publications were from China and USA. The University Copenhagen and Shanghai Jiao Tong University were the most active institutions. The journal of Nutrients published the most papers, while Nature was the top 1 co-cited journal, and the major area of these publications was molecular, biology, and immunology. Nieuwdorp M published the highest number of papers, and Cani PD had the highest co-citations. Keyword analysis showed that the most frequently occurring keywords were "gut microbiota", "insulin-resistance", "obesity", and "inflammation". Trend topics and thematic maps showed that serum metabolome and natural products, such as resveratrol, flavonoids were the research hotspots in this field. Conclusion: This bibliometric analysis summarised the hotspots, frontiers, pathogenesis, and treatment strategies, providing a clear and comprehensive profile of gut microbiota in IR. Supplementary Information: The online version contains supplementary material available at 10.1007/s40200-023-01342-x.

A multifunctional fluorescent probe for sequential detection of hydrogen sulfide and pH in foodstuffs, living cells and mice.

BACKGROUND: Cancer as a leading cause of premature death worldwide has become a major threat to human health due to the high incidence and mortality. Monitoring tumor markers are reliable and significantly important for early detection of cancers. In complex biological systems, it is of great urgency but still remains challenging to conceive a fluorescent probe with multiple tumor markers detection property. Hydrogen sulfide (H2S) and pH are two target biomarkers for diagnosis of early cancer. The preparation of a novel probe with H2S and pH dual detection functions is highly anticipated. RESULTS: Herein, a novel sequential detection probe HTPQ-HS for H2S and pH has been developed. In this system, HPQ (2-(2 -hydroxyphenyl)-4(3H)-quinazolinone) structure combined with triphenylamine is applied as the fluorophore, and 2, 4-dinitrophenylsulfonyl group is used as the recognition group. In the presence of H2S, HTPQ-HS is transformed into product HTPQ-OH which shows fluorescence enhancement (29-fold) at 525 nm in less than 4 min and further displays repeatable acid-base responsive ability. HTPQ-HS is able to sequentially response to H2S and pH in living cells and does not react directly with pH. Owing to the low cytotoxicity, HTPQ-HS is able to detect exogenous and endogenous H2S in colon cancer cells and mice, monitor H2S in inflammation model and in foodstuffs. As the environment changes from acidic to alkaline, the fluorescence intensity ratio (I470/I530) of product HTPQ-OH changes remarkably, illustrating the ratiometric fluorescent responsiveness to pH. SIGNIFICANCE AND NOVELTY: A multifunctional fluorescent probe HTPQ-HS for sequential detection of H2S and pH is synthesized. Probe HTPQ-OH realizes the monitoring of dynamic changes in intracellular pH and displays prospective application in security printing. We expect that our work could offer an important guidance on the development of multifunctional fluorescent probes for visualizing H2S and pH in biology and environment.

A lysosome-targeted fluorescent probe based on a BODIPY structure for Cys/Hcy detection.

Cysteine (Cys) and homocysteine (Hcy) are important biothiols in living organisms. They play important roles in a variety of physiological and pathological processes. Therefore, it is very important to design an optical probe for the selective detection of Cys/Hcy. Herein, we report the design and synthesis of a fluorescent probe NBD-B-T based on a boron-dipyrromethene (BODIPY) structure, which showed an excellent lysosome targeting ability and an outstanding Cys/Hcy detection capacity. For NBD-B-T, the sensing group 7-nitro-2,1,3-benzoxadiazole (NBD) and the lysosomal targeting group morpholine were introduced. The results show that the NBD-B-T probe can detect Cys/Hcy with fluorescence emission turn-on performance. The low detection limits of this probe are about 76.0 nM for Hcy and 97.6 nM for Cys, respectively. The NBD-B-T probe has a low detection limit, high stability, and excellent selectivity and sensitivity. More importantly, the NBD-B-T can target lysosome, and simultaneously detect the Cys/Hcy in living cells.

Sources, morphology, phytochemistry, pharmacology of Curcumae Longae Rhizoma, Curcumae Radix, and Curcumae Rhizoma: a review of the literature.

Curcumae Longae Rhizoma (turmeric), Curcumae Radix and Curcumae Rhizoma are derived from the Curcuma species, and have gradually become three of the most commonly used medicinal herbs in China due to their different origins, processing methods and medicinal part. These three herbs have certain similarities in morphology, chemical composition, and pharmacological effects. All three of these herbs contain curcuminoids and volatile oil compounds, which exhibit anti-inflammatory, anti-tumor, antioxidant, and neuroprotective properties, although modern clinical applications have their own requirements. At present, there is no systematic guidelines for the clinical application of these three of Curcuma species; consequently, there is a high risk of unwanted phenomena associated with the mixing and indiscriminate use of these herbs. In this review, we focus predominantly on morphology, chemical composition, and the pharmacological activity of these three Curcuma herbs and summarize the current status of research in this field. Our goal is to provide a better understanding of clinical value of these Curcuma species so that we can provide reference guidelines for their further development, utilization and rational clinical application.

LC-MS-based metabolomics reveals the mechanism of anti-gouty arthritis effect of Wuwei Shexiang pill.

Wuwei Shexiang Pill (WSP) is a Tibetan traditional medicine, which has been demonstrated to exhibit potent anti-inflammatory and anti-gout effects. However, the specific pharmacological mechanism is not elucidated clearly. In the present study, liquid chromatography-mass spectrometry (LC-MS)-based metabolomics was applied to investigate the alteration of serum metabolites induced by WSP treatment in MSU-induced gouty rats. Subsequently, bioinformatics was utilized to analyze the potential metabolic pathway of the anti-gout effect of WSP. The pharmacodynamic data discovered that WSP could ameliorate ankle swelling and inflammatory cell infiltration, as well as downregulate the protein expression of IL-1ß, p-NF-κB p65, and NLRP3 in the synovial membrane and surrounding tissues of gouty ankles. LC-MS-based metabolomics revealed that there were 30 differential metabolites in the serum between sham-operated rats and gouty ones, which were mainly involved in the metabolism of fructose and mannose, primary bile acid biosynthesis, and cholesterol metabolism. However, compared to the model group, WSP treatment upregulated 11 metabolic biomarkers and downregulated 31 biomarkers in the serum. KEGG enrichment analysis found that 27 metabolic pathways contributed to the therapeutic action of WSP, including linoleic acid metabolism, phenylalanine metabolism, and pantothenate and CoA biosynthesis. The comprehensive analysis-combined network pharmacology and metabolomics further revealed that the regulatory network of WSP against gout might be attributed to 11 metabolites, 7 metabolic pathways, 39 targets, and 49 active ingredients of WSP. In conclusion, WSP could ameliorate the inflammation of the ankle in MSU-induced gouty rats, and its anti-gout mechanism might be relevant to the modulation of multiple metabolic pathways, such as linoleic acid metabolism, phenylalanine metabolism, and pantothenate and CoA biosynthesis. This study provided data support for the secondary development of Chinese traditional patent medicine.

Polypeptide from Moschus Suppresses Lipopolysaccharide-Induced Inflammation by Inhibiting NF-κ B-ROS/NLRP3 Pathway.

OBJECTIVE: To examine the anti-inflammatory effects and potential mechanisms of polypeptide from Moschus (PPM) in lipopolysaccharide (LPS)-induced THP-1 macrophages and BALB/c mice. METHODS: The polypeptide was extracted from Moschus and analyzed by high-performance liquid chromatography and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Subsequently, LPS was used to induce inflammation in THP-1 macrophages and BALB/c mice. In LPS-treated or untreated THP-1 macrophages, cell viability was observed by cell counting kit 8 and lactate dehydrogenase release assays; the proinflammatory cytokines and reactive oxygen species (ROS) were measured by enzyme-linked immunosorbent assay and flow cytometry, respectively; and protein and mRNA levels were measured by Western blot and real-time quantitative polymerase chain reaction (qRT-PCR), respectively. In LPS-induced BALB/c mice, the proinflammatory cytokines were measured, and lung histology and cytokines were observed by hematoxylin and eosin (HE) and immunohistochemical (IHC) staining, respectively. RESULTS: The SDS-PAGE results suggested that the molecular weight of purified PPM was in the range of 10-26 kD. In vitro, PPM reduced the production of interleukin 1ß (IL-1ß), IL-18, tumor necrosis factor α (TNF-α), IL-6 and ROS in LPS-induced THP-1 macrophages (P<0.01). Western blot analysis demonstrated that PPM inhibited LPS-induced nuclear factor κB (NF-κB) pathway and thioredoxin interacting protein (TXNIP)/nucleotide-binding oligomerization domain, leucine-rich repeat and pyrin domain containing 3 (NLRP3) inflammasome pathway by reducing protein expression of phospho-NF-κB p65, phospho-inhibitors of NF-κB (Iκ Bs) kinase α/ß (IKKα/ß), TXNIP, NLRP3, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), and pro-caspase-1 (P<0.05 or P<0.01). In addition, qRT-PCR revealed the inhibitory effects of PPM on the mRNA levels of TXNIP, NLRP3, ASC, and caspase-1 (P<0.05 or P<0.01). Furthermore, in LPS-induced BALB/c mice, PPM reduced TNF-α and IL-6 levels in serum (P<0.05 or P<0.01), decreased IL-1ß and IL-18 levels in the lungs (P<0.01) and alleviated pathological injury to the lungs. CONCLUSION: PPM could attenuate LPS-induced inflammation by inhibiting the NF-κB-ROS/NLRP3 pathway, and may be a novel potential candidate drug for treating inflammation and inflammation-related diseases.

A copper complex that combats triple negative breast cancer by restraining angiogenesis.

Angiogenesis and metastasis are major factors affecting the growth and invasion of triple negative breast cancer (TNBC). A phenanthroline copper(II) complex CPT8 modified with an alkyl chain-linked triphenylphosphonium group showed potent antiproliferative activity against a series of cancer cells including TNBC MDA-MB-231 cells. CPT8 induced mitophagy through activation of PINK1/Parkin and BNIP3 pathways in cancer cells due to damage to mitochondria. More importantly, CPT8 reduced the tube formation ability of human umbilical vein endothelial cells (HUVEC) through downregulation of nuclear factor erythroid 2-related factor 2 (Nrf2). The anti-angiogenic potential of CPT8 was confirmed by decreased vascular endothelial growth factor (VEGF) and CD34 expression in HUVEC. Moreover, CPT8 suppressed the expression of vascular endothelial cadherin and matrix metalloproteinases MMP2 and MMP9, leading to the inhibition of vasculogenic mimicry formation. CPT8 also weakened the metastatic potential of MDA-MB-231 cells. Downregulation of Ki67 and CD34 expression indicates that CPT8 suppressed tumor proliferation and vascularization in vivo, thus providing a unique metal drug candidate for the treatment of TNBC.

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.

Mechanism Investigation of Wuwei Shexiang Pills on Gouty Arthritis via Network Pharmacology, Molecule Docking, and Pharmacological Verification.

Background: Gout is a common crystal-related arthritis caused by the deposition of monosodium urates (MSU). Tibetan medicine Wuwei Shexiang Pills (WSP) has been demonstrated to exhibit anti-inflammatory, antihyperuricemia, and antigout activities. However, the underlying mechanism is unknown. Objectives: To explore the mechanisms of Wuwei Shexiang Pills on gouty arthritis via network pharmacology, molecule docking, and pharmacological verification. Methods: The ingredients and targets of WSP were obtained by searching and screening in BATMAN-TCM and SwissADME. The targets involving the gout were acquired from public databases. The shared targets were put onto STRING to construct a PPI network. Furthermore, Metascape was applied for the GO and KEGG enrichment analysis to predict the biological processes and signaling pathways. And molecular docking was performed to validate the binding association between the key ingredients and the relative proteins of TNF signaling. Based on the serum pharmacology, the predicted antigout mechanism of WSP was validated in MSU-induced THP-1 macrophages. The levels of inflammatory cytokines and mRNA were measured by ELISA and qRT-PCR, respectively, and MAPK, NF-κB, and NLRP3 signaling-associated proteins were determined by western blot and immunofluorescence staining. Results: 48 bioactive ingredients and 165 common targets were found in WSP. The data showed that 5-Cis-Cyclopentadecen-1-One, 5-Cis-Cyclotetradecen-1-One, (-)-isoshyobunone, etc. were potential active ingredients. TNF signaling, HIF-1 signaling, and Jak-STAT signaling were predicted to be the potential pathways against gout. The molecule docking analysis found that most ingredients had a high affinity for p65, NLRP3, IL-1ß, TNF-α, and p38. The data from in vitro experiment showed that WSP suppressed the production and gene expression of inflammatory cytokines. Furthermore, WSP could inhibit the activation of MAPK, NF-κB, and NLRP3 signaling pathways. Conclusion: Our finding suggested that the antigout effect of WSP could be achieved by inhibiting MAPK, NF-κB, and NLRP3 signaling pathways. WSP might be a candidate drug for gouty treatment.

The gut-lung axis: Gut microbiota changes associated with pulmonary fibrosis in mouse models induced by bleomycin.

The main objective of this study was to investigate the alterations in the gut microbiota (GM) of pulmonary fibrosis (PF) mice induced by bleomycin (BLM) with its underlying mechanisms. BLM was docked with the targets of TGF-ß/SMAD and caspase-3 pathways using the molecular docking technique. HE staining and Masson staining were applied to observe the histopathological changes in the pulmonary tissues. Detection of the apoptotic signals was conducted by flow cytometry and TUNEL staining. The mRNA expression of targets involved in the TGF-ß/SMAD and caspase-3 signaling pathways in lungs was determined by qPCR. Immunohistochemistry (IHC) assay was used to detect the expression levels of cleaved caspase-3 and BAX proteins in mice lung tissues. 16S rDNA sequencing analysis was used to investigate the changes of GM in the fecal samples of mice in each group. The results showed that the apoptosis rate of pulmonary cells in the BLM group distinctly increased, with the expression levels of crucial target pro-apoptotic gene caspase-3, BAX with the corresponding protein, cleaved caspase-3, BAX were apparently elevated. This was accompanied by a significant increase in pro-fibrotic targets level such as TGF-ß, fibronectin, collagen I, and collagen III. The mechanisms of PF induced by BLM were related to apoptosis of lung tissue cells such as alveolar epithelial cells and destroyed alveolar structure and excessive production of extracellular matrix (ECM), which may be bound up with activating TGF-ß/SMAD and caspase-3 pathways. As for the GM, it was found that, after BLM induced PF in mice, the micro ecological balance of the GM was destroyed; the distance of PCo1 and Pco2 was significantly elongated, and the relative abundance of some intestinal probiotics like Catenibacterium and Lactobacillus (L. johnsonii and L. gasseri) dramatically lowered while the relative abundance of Verrucomicrobiales and Enterobacteriales substantially increased. Therefore, GM changes associated with PF in mouse models induced by BLM and the concept of "gut-lung axis" might provide an optional therapeutic strategy for PF.

[Mystery of Yiyin decoction theory: rule discovery and evaluation strategy of atypical pharmacological effects of Chinese medicinal prescription].

Yi Yin, a famous medical scientist and culinary master in the late Xia Dynasty and early Shang Dynasty, developed the Chinese medicinal liquids and Chinese medicinal prescriptions emerged after that. Chinese medicinal prescriptions have attracted much attention because of their unique advantages in the treatment of chronic multifactorial diseases, representing an important direction of drug discovery in the future. Yiyin decoction theory is the superior form of personalized combined medication with advanced consciousness. It is different from not only the magic bullet theory of single component action but also the connotation of modern multi-target drugs. The core of Yiyin decoction theory can be summarized as compound compatibility, multiple effects, and moderate regulation. Compound compatibility refers to that the formulation of Chinese medicinal prescriptions involves the complex synergy and interactions between sovereign, minister, assistant, and guide medicinal materials. Multiple effects mean that the prescriptions employ a variety of mechanisms to exert comprehensive pharmacological effects of nonlinear feedback. Moderate regulation reflects that the prescriptions can accurately regulate the multiple points of the disease biological network as a whole. To solve the mystery of Yiyin decoction theory, we should not only simply study the known active substances(components) and their independent target effects in the mixture, but also mine the "dark matter" and "dark effect" of Chinese medicinal prescriptions. That is, we should learn the neglected atypical pharmacological effects of Chinese medicinal prescriptions and the multi-point nesting mechanism that plays a precise regulatory function in the body. Yiyin decoction theory focuses on the overall pharmacological effect to reflect the comprehensive clinical value of Chinese medicinal prescriptions, which is of great significance for the development of a new model for the evaluation and application of new Chinese medicinal prescriptions in line with the theory of traditional Chinese medicine.

The Cascade [1,5]-Hydride Shift/Intramolecular C(sp3)-H Activation: A Powerful Approach to the Construction of Spiro-Tetrahydroquinoline Skeleton.

The direct functionalization of inert C-H bonds is regarded as one of the most powerful strategies to form various chemical bonds and construct complex structures. Although significant advancements have been witnessed in the area of transition metal-catalyzed functionalization of inert C-H bonds, several challenges, such as the utilization and removal of expensive transition metal complexes, limited substrate scope and large-scale capacity, and poor atom economy in removing guiding groups coordinated to the transition metal, cannot fully fulfill the high standard of modern green chemistry nowadays. Over the past decades, due to its inherent advantage compared with a transition metal-catalyzed strategy, the hydride shift activation that applies "tert-amino effect" into the direct functionalization of the common and omnipresent C(sp3)-H bonds adjacent to tert-amines has attracted much attention from the chemists. In particular, the intramolecular [1,5]-hydride shift activation, as the most common hydride shift mode, enables the rapid and effective production of multifunctionally complex frameworks, especially the spiro-tetrahydroquinoline derivatives, which are widely found in biologically active natural products and pharmaceuticals. Although great accomplishments have been achieved in this promising field, rarely an updated review has systematically summarized these important progresses despite scattered reports documented in several reviews. Hence, in this review, we will summarize the significant advances in the cascade [1,5]-hydride shift/intramolecular C(sp3)-H functionalization from the perspective of "tert-amino effect" to build a spiro-tetrahydroquinoline skeleton, and the content is categorized by structure type of final spiro-tetrahydroquinoline products containing various pharmaceutical units. Besides, current limitations as well as future directions in this field are also pointed out. We hope our review could provide a quick look into and offer some inspiration for the research on hydride shift strategy in the future.

Berberine prevents diabetic retinopathy through inhibiting HIF-1α /VEGF/ NF-κ B pathway in db/db mice.

Our paper investigated the effect of berberine on the diabetic retinopathy (DR) in db/db transgenic mice and explored its possible mechanisms. During chronic intragastric administration for ten weeks, berberine could decrease the levels of fasting blood glucose, TC and TG without hepatotoxicity. Moreover, berberine could protect the retinal morphology against the hyperglycemic insults and decrease glycogen accumulation, the contents of TNF-α and IL-1ß in the retinas, as demonstrated by HE staining, PAS staining and ELISA kits, respectively. Immunofluorescence assay revealed that the protein expression of vascular endothelial growth factor (VEGF), VEGF receptor 2, hypoxia-inducible factor-1α(HIF-1α), and nuclear factor-κ B (NF-κB) p65 was upregulated in db/db retinas compared with wild type ones, whereas berberine treatment could suppress their expression. Berberine prevent DR development through modulating the glucolipid metabolism and inhibiting the HIF-1α /VEGF/NF-κ B pathway, suggesting that berberine maybe a potential agent for the treatment of DR.

Bulbus Fritillariae Cirrhosae as a Respiratory Medicine: Is There a Potential Drug in the Treatment of COVID-19?

Bulbus fritillariae cirrhosae (BFC) is one of the most used Chinese medicines for lung disease, and exerts antitussive, expectorant, anti-inflammatory, anti-asthmatic, and antioxidant effects, which is an ideal therapeutic drug for respiratory diseases such as ARDS, COPD, asthma, lung cancer, and pulmonary tuberculosis. Through this review, it is found that the therapeutic mechanism of BFC on respiratory diseases exhibits the characteristics of multi-components, multi-targets, and multi-signaling pathways. In particular, the therapeutic potential of BFC in terms of intervention of "cytokine storm", STAT, NF-κB, and MAPK signaling pathways, as well as the renin-angiotensin system (RAS) that ACE is involved in. In the "cytokine storm" of SARS-CoV-2 infection there is an intense inflammatory response. ACE2 regulates the RAS by degradation of Ang II produced by ACE, which is associated with SARS-CoV-2. For COVID-19, may it be a potential drug? This review summarized the research progress of BFC in the respiratory diseases, discussed the development potentiality of BFC for the treatment of COVID-19, explained the chemical diversity and biological significance of the alkaloids in BFC, and clarified the material basis, molecular targets, and signaling pathways of BFC for the respiratory diseases. We hope this review can provide insights on the drug discovery of anti-COVID-19.

A review of the processed Polygonum multiflorum (Thunb.) for hepatoprotection: Clinical use, pharmacology and toxicology.

ETHNOPHARMACOLOGICAL RELEVANCE: Polygonum multiflorum (Thunb.) (PMT) is a member of Polygonaceae. Traditional Chinese medicine considers that the processed PMT can tonify liver, nourish blood and blacken hair. In recent years, the processed PMT and its active ingredients have significant therapeutic effects on nonalcoholic fatty liver disease, alcoholic fatty liver disease, viral hepatitis, liver fibrosis and liver cancer. AIM OF THE STUDY: The main purpose of this review is to provide a critical appraisal of the existing knowledge on the clinical application, hepatoprotective pharmacology and hepatotoxicity, it provides a comprehensive evaluation of the liver function of the processed PMT. MATERIALS AND METHODS: A detailed literature search was conducted using various online search engines, such as Pubmed, Google Scholar, Mendeley, Web of Science and China National Knowledge Infrastructure (CNKI) database. The main active components of the processed PMT and the important factors in the occurrence and development of liver diseases are used as key words to carry out detailed literature retrieval. RESULTS: In animal and cell models, the processed PMT and active components can treat various liver diseases, such as fatty liver induced by high-fat diet, liver injury and fibrosis induced by drugs, viral transfected hepatitis, hepatocellular carcinoma, etc. They can protect liver by regulating lipid metabolism related enzymes, resisting insulin resistance, decreasing the expression of inflammatory cytokines, inhibiting the activation of hepatic stellate cells, reducing generation of extracellular matrix, promoting cancer cell apoptosis and controlling the growth of tumor cells, etc. However, improperly using of the processed PMT can cause liver injury, which is associated with the standardization of processing, the constitution of the patients, the characteristics of the disease, and the administration of dosage and time. CONCLUSION: The processed PMT can treat various liver diseases via reasonably using, and the active compounds (2,3,5,4'-tetrahydroxystilbene-2-O-ß-D-glucoside, emodin, physcion, etc.) are promising candidate drugs for developing new liver protective agents. However, some components have a "toxic-effective" bidirectional effect, which should be used cautiously.

Aloe emodin induces hepatotoxicity by activating NF-κB inflammatory pathway and P53 apoptosis pathway in zebrafish.

The aim of this study was to investigate the hepatotoxic effect and its underlying mechanism of aloe emodin (AE). AE was docked with the targets of NF-κB inflammatory pathway and P53 apoptosis pathway respectively by using molecular docking technique. To verify the results of molecular docking and further investigate the hepatotoxicity mechanism of AE, the zebrafish Tg (fabp10: EGFP) was used as an animal model in vivo. The pathological sections of zebrafish liver were analyzed to observe the histopathological changes and Sudan black B was used to study whether there were inflammatory reactions in zebrafish liver or not. Then TdT-mediated dUTP Nick-End Labeling (TUNEL) was used to detect the apoptotic signal of zebrafish liver cells, finally the mRNA expression levels as well as the protein expression levels of the targets in NF-κB and P53 pathways in zebrafish were measured by quantitative Real-Time PCR (qRT-PCR) and western blot. Molecular docking results showed that AE could successfully dock with all the targets of NF-κB and P53 pathways, and the docking scores of most of the targets were equal to or higher than that of the corresponding ligands. Pathological sections showed AE could cause zebrafish liver lesions and the result of Sudan black B staining revealed that AE blackened the liver of zebrafish with Sudan black B. Then TUNEL assay showed that a large number of dense apoptotic signals were observed in AE group, mainly distributed in the liver and yolk sac of zebrafish. The results of qRT-PCR and western blot showed that AE increased the mRNA and protein expression levels of pro-inflammatory and pro-apoptotic targets in NF-κB and P53 pathways. AE could activate the NF-κB inflammatory pathway and the P53 apoptosis pathway, and its hepatotoxic mechanism was related to activation of NF-κB-P53 inflammation-apoptosis pathways.

Resveratrol-loaded PLGA nanoparticles: enhanced stability, solubility and bioactivity of resveratrol for non-alcoholic fatty liver disease therapy.

Resveratrol (3, 4', 5-trihydroxy-trans-stilbene, RSV), a nutraceutical, has recently attracted lots of attention because of its outstanding pharmacological potential. The effects of RSV on non-alcoholic fatty liver disease (NAFLD) remain inconclusive, although a wealth of research has been done. The major obstacle presented was RSV's poor bioavailability due to its poor aqueous solubility, chemical instability and intestinal metabolism. In this study, nanotechnology was used to encapsulate RSV to enhance its stability, water solubility and bioactivity, which can be used to treat NAFLD by HepG2 hepatocytes-induced in vitro. RSV-loaded poly (d, l-lactide-co-glycolide acid) (PLGA) nanoparticles (RSV-PLGA-NPs) were prepared according to an oil/water (O/W) emulsion technique. The RSV-PLGA-NPs were of spherical morphology with an average size of 176.1 nm and a negative charge of -22.6 mV. These nanoparticles exhibited remarkable encapsulation efficiency (EE%) (97.25%) and drug loading (14.9%) for RSV. A sustained RSV release from RSV-PLGA-NPs could be achieved especially in acidic conditions when simulating transporting through the gastrointestinal tract. In addition, these nanoparticles were stable enough to store at 4°C for a least six months with unchanged EE%. Moreover, RSV-PLGA-NPs were more efficient in alleviating lipogenesis, promoting lipolysis and reducing hepatocellular proliferation than free RSV due to its improved stability, water solubility and bioactivity. These findings indicated that the RSV-PLGA-NPs provided superb and stable drug delivery with small particle size, high capsulation efficiency, well-controlled drug release, which greatly enhanced the stability, water solubility and bioactivity. Besides, the discovery that the inhibitory effect of RSV-PLGA-NPs on hepatocellular proliferation and lipid accumulation in steatotic HepG2 cells may provide a new way to study the mechanism of NAFLD. Therefore, RSV-PLGA-NPs have a promising potential for NAFLD therapy.

Experimental study of the protective effect of mesosilica-supported 5-hydroxymethylfurfural on UV-induced aging of human dermal fibroblasts.

The drug 5-HMF (5-hydroxymethylfurfural, C6H6O3) is extensively studied for its antioxidative and anti-inflammatory properties. However, its unstable properties and biotoxicity restrict its use in skin care products and therapy. The present study was aimed at evaluating the potential of three-dimensional dendritic mesoporous silica nanospheres (3D-dendritic MSNs) as a topical carrier system for 5-HMF delivery. The encapsulation of the carrier also enhances the stability of the drug. Based on the results of Brunauer-Emmet-Teller (BET) analysis, Fourier transform infrared spectroscopy (FTIR), transmission electron microscopy (TEM), thermogravimetric analysis (TGA), dynamic light scattering (DLS), and UV-vis diffuse reflectance spectroscopy, drug delivery systems were successfully fabricated and the loading capacity (LC%) and entrapment efficiency (EE%) were also assessed. In vitro cell tests revealed the outstanding biocompatibility and inoxidizability of 3D-dendritic MSNs. There is no effect on the antioxidant properties of the drug. Therefore, mesoporous silica can be combined with 5-HMF and used as potential antioxidant medicine in cosmetic applications.

A Cell-Based Metabonomics Approach to Investigate the Varied Influences of Chrysophanol-8-O-ß-D-Glucoside With Different Concentrations on L-02 Cells.

In this study, the effects of different concentrations of chrysophanol-8-O-ß-D-glucoside (C-8-O-ß-D-glu) on L-02 liver cells were analyzed by high content analysis (HCA) and metabonomics to explore the potential mechanism involved. The results showed that low concentrations (12 and 24 µM) of C-8-O-ß-D-glu increased the cells viability significantly, while high concentration (96 µM) showed significant cytotoxicity on L-02 cells. HCA was applied to analyze the changes of nuclei and mitochondria after the cells being exposed to C-8-O-ß-D-glu for 24 h. The results showed high concentration (96 µM) of C-8-O-ß-D-glu significantly reduced the number of living cells, increased average nucleus area, DNA content and mitochondrial membrane potential (MMP). Then non-target metabonomics was carried out to identify potential biomarkers and metabolic pathways of L-02 cells impacted by C-8-O-ß-D-glu. Eleven important potential biomarkers associated with four metabolic pathways were identified in this analysis. Dysregulation of alanine, aspartate and glutamate metabolism were observed in both LCG and HCG. In addition, low concentration (24 µM) of C-8-O-ß-D-glu would impact arginine and proline metabolism. High concentration (96 µM) of C-8-O-ß-D-glu would impact phenylalanine metabolism and beta-alanine metabolism. Alanine, aspartate and glutamate metabolism, arginine and proline metabolism, phenylalanine metabolism, beta-alanine metabolism were involved in different effects of C-8-O-ß-D-glu on L-02 cells.

Self-cleaning of Surfaces: the Role of Surface Wettability and Dust Types.

The self-cleaning property is usually connected to superhydrophobic surfaces (SHSs) where the dust particles can be easily removed by the rolling motion of droplets. It seems that superhydrophobicity (its durability is questionable nowadays) is a necessity. However here, it is disclosed that self-cleaning can also be realized on an ordinary surface by droplet impinging. The effects of surface wettability and the types of dust particles are considered. The self-cleaning is realized by two steps: (1) the pickup of particles by the water-air interface of an impinging droplet, (2) the release of the impinging droplets from the surface. It can be observed that only the trailing edges of the droplets can pick up particles when the droplets recoil from the inclined surfaces. The hydrophilic surface can also achieve self-cleaning under some conditions. This interesting finding may be helpful for the successful implementation of self-cleaning with common surfaces.