Bionic nanotheranostic for multimodal imaging-guided NIR-II-photothermal cancer therapy.

In photothermal therapy (PTT), the photothermal conversion of the second near-infrared (NIR-II) window allows deeper penetration and higher laser irradiance and is considered a promising therapeutic strategy for deep tissues. Since cancer remains a leading cause of deaths worldwide, despite the numerous treatment options, we aimed to develop an improved bionic nanotheranostic for combined imaging and photothermal cancer therapy. We combined a gold nanobipyramid (Au NBP) as a photothermal agent and MnO2 as a magnetic resonance enhancer to produce core/shell structures (Au@MnO2; AM) and modified their surfaces with homologous cancer cell plasma membranes (PM) to enable tumour targeting. The performance of the resulting Au@MnO2@PM (AMP) nanotheranostic was evaluated in vitro and in vivo. AMP exhibits photothermal properties under NIR-II laser irradiation and has multimodal in vitro imaging functions. AMP enables the computed tomography (CT), photothermal imaging (PTI), and magnetic resonance imaging (MRI) of tumours. In particular, AMP exhibited a remarkable PTT effect on cancer cells in vitro and inhibited tumour cell growth under 1064 nm laser irradiation in vivo, with no significant systemic toxicity. This study achieved tumour therapy guided by multimodal imaging, thereby demonstrating a novel strategy for the use of bionic gold nanoparticles for tumour PTT under NIR-II laser irradiation.

Exploring the pharmacological mechanisms and key active ingredients of total flavonoids from Lamiophlomis rotata (Benth.) Kudo against rheumatoid arthritis based on multi-technology integrated network pharmacology.

ETHNOPHARMACOLOGICAL RELEVANCE: Lamiophlomis rotata (Benth.) Kudo (LR, Lamiaceae) is a traditional Tibetan medicinal material in China. Tibetan medicine classic and research report suggested that LR could be used to cure rheumatoid arthritis (RA). However, the anti-RA active ingredients and pharmacological mechanisms of LR have not been elucidated. AIM OF THE STUDY: To explore the mechanisms and key active ingredients of total flavonoids from LR (TFLR) against RA. MATERIALS AND METHODS: First, the mechanisms of TFLR against RA were investigated on collagen-induced arthritis (CIA) rat model by analyzing paw appearance, paw swelling, arthritis score, spleen index, thymus index, inflammatory cytokine (TNF-α, IL-1ß, IL-6 and IL-17) levels in serum, histopathology of ankle joint and synovium from knee joint (hematoxylin-eosin, safranin O-fast green and DAB-TUNEL staining), and apoptosis-related protein (PI3K, Akt1, p-Akt, Bad, p-Bad, Bcl-xL and Bcl-2) levels in the synovium of ankle joints (Western blot). Then, the crucially active ingredients of TFLR against RA were explored by network pharmacology, ingredient analysis, in vitro metabolism and TNF-α-induced human RA synovial fibroblast MH7A proliferation assays. Network pharmacology was applied to predict the key active ingredients of TFLR against RA. The ingredient analysis and in vitro metabolism of TFLR were performed on HPLC, and MH7A proliferation assay were applied to evaluate the predicted results of network pharmacology. RESULTS: TFLR shown excellently anti-RA effect by reducing paw swelling, arthritis score, spleen index, thymus index and inflammatory cytokine (IL-1ß, IL-6 and IL-17) levels, and improving the histopathological changes of ankle joint and synovium from knee joint in CIA rats. Results of Western blot indicated that TFLR reversed the changes of PI3K, p-Akt, p-Bad, Bcl-xL and Bcl-2 levels in the ankle joint synovium of CIA rats. Results of network pharmacology exhibited that luteolin was identified as the pivotal active ingredient of TFLR against RA. The ingredient analysis of TFLR indicated that the main ingredient in TFLR was luteoloside. The in vitro metabolism study of TFLR suggested that luteoloside could be converted to luteolin in artificial gastric juice and intestinal juice. Results of MH7A proliferation assay showed that there was no significant difference between TFLR and equal luteoloside on the viability of MH7A cells, indicating that luteoloside was the key active ingredient of TFLR against RA. Additionally, the luteolin (same mol as luteoloside) showed better inhibitory effect on the viability of MH7A cells than luteoloside. CONCLUSION: TFLR showed anti-RA effect, and the mechanism was related to promoting synovial cell apoptosis mediated by PI3K/Akt/Bad pathway. Meanwhile, this work indicated that luteoloside was the key active ingredient of TFLR against RA. This work lays a foundation for providing TFLR product with clear mechanism and stable quality to treat RA.

Gold nanobipyramid@copper sulfide nanotheranostics for image-guided NIR-II photo/chemodynamic cancer therapy with enhanced immune response.

Photothermal therapy (PTT), photodynamic therapy (PDT), and chemodynamic therapy (CDT) can cause cancer cell death through an immunogenic process. However, the study of second near-infrared window (NIR-II)-triggered PTT and PDT combined with CDT to induce an immune response has not been recently reported. Here, we integrated gold nanobipyramids and copper sulfide in a core/shell architecture (AuNBP@CuS). The material displays both photodynamic and photothermal properties under irradiation with a NIR-II laser. The released Cu2+ from CuS under an acidic tumor microenvironment can be converted to Cu+ by glutathione following a Fenton-like reaction with hydrogen peroxide to generate highly toxic hydroxyl radicals in the tumor region. Both in vitro and in vivo results demonstrated that such multifunctional nanoplatforms could achieve enhanced efficiency for image-guided tumor suppression based on the NIR-II photo/chemodynamic therapy. We found that damage-associated molecular pattern molecules such as adenosine triphosphate, pre-apoptotic calreticulin, and high mobility group box-1 in dying cells induced by the NIR-II photo/chemodynamic therapy could simultaneously trigger adaptive immune responses. This is the first report revealing that NIR-II photo/chemodynamic therapy based on AuNBP@CuS had promising performance on tumor suppressor with an effective immunogenic cell death process. STATEMENT OF SIGNIFICANCE: 1. AuNBP@CuS displays both NIR-II photodynamic and photothermal properties. 2. Cu+ following a Fenton-like reaction to generate highly toxic hydroxyl radicals. 3. The NIR-II photo/chemodynamic therapy can trigger adaptive immune responses. 4. Such multifunctional nanoplatforms could achieve enhanced efficiency for tumor suppression.

The chloroplasts genomic analyses of four specific Caragana species.

BACKGROUND: Many species of the genus Caragana have been used as wind prevention and sand fixation plants. They are also important traditional Chinese medicine, and ethnic medicine resource plant. Thus, chloroplast genomes (cp-genome) of some of these important species must be studied. METHODS: In this study, we analyzed the chloroplast genomes of C. jubata, C. erinacea, C. opulens, and C. bicolor, including their structure, repeat sequences, mutation sites, and phylogeny. RESULTS: The size of the chloroplast genomes was between 127,862 and 132,780 bp, and such genomes contained 112 genes (30 tRNA, 4 rRNA, and 78 protein-coding genes), 43 of which were photosynthesis-related genes. The total guanine + cytosine (G+C) content of four Caragana species was between 34.49% and 35.15%. The four Caragana species all lacked inverted repeats and can be classified as inverted repeat-lacking clade (IRLC). Of the anticipated genes of the four chloroplast genomes, introns were discovered in 17 genes, most of which were inserted by one intron. A total of 50 interspersed repeated sequences (IRSs) were found among them, 58, 29, 61, and 74 simple sequences repeats were found in C. jubata, C. bicolor, C. opulens, and C. erinacea, respectively. Analyses of sequence divergence showed that some intergenic regions (between trnK-UUU and rbcl; trnF-GAA and ndhJ; trnL-CAA and trnT-UGU; rpoB and trnC-GCA; petA and psbL; psbE and pebL; and sequences of rpoC, ycf1, and ycf2) exhibited a high degree of variations. A phylogenetic tree of eight Caragana species and another 10 legume species was reconstructed using full sequences of the chloroplast genome. CONCLUSIONS: (1) Chloroplast genomes can be used for the identification and classification of Caragana species. (2) The four Caragana species have highly similar cpDNA G+C content. (3) IRS analysis of the chloroplast genomes showed that these four species, similar to the chloroplast genome of most legumes, lost IRLC regions. (4) Comparative cp-genomic analysis suggested that the cp genome structure of the Caragana genus was well conserved in highly variable regions, which can be used to exploit markers for the identification of Caragana species and further phylogenetic study. (5) Results of phylogenetic analyses were in accordance with the current taxonomic status of Caragana. The phylogenetic relationship of Caragana species was partially consistent with elevation and geographical distribution.

All-In-One Second Near-Infrared Light-Responsive Drug Delivery System for Synergistic Chemo-Photothermal Therapy.

Light-responsive nanocarrier-based drug delivery systems (NDDSs), due to their unique advantages such as safety, minimal cross-reaction, and spatiotemporal precision, have received wide attention. Notably, second near-infrared (NIR-II) light, which has a high penetration depth for manipulating NDDSs to release drugs, is in high demand. Herein, polyethylene glycol (PEG)-modified hollow CuxS nanoparticles (NPs) are developed as an all-in-one NIR-II light-responsive NDDS for synergistic chemo-photothermal therapy. First, CuxS-PEG NPs were prepared under mild conditions by using Cu2O NPs as sacrificial templates. The morphology, photothermal effect, drug loading/releasing abilities, and synergistic chemo-photothermal therapy of CuxS-PEG NPs have been investigated. The CuxS-PEG NPs with hollow structures showed a high drug loading capacity (∼255 µg Dox per mg of CuxS NPs) and stimuli-responsive drug release triggered by NIR-II laser irradiation. The synergistic chemo-photothermal therapy based on the Dox/CuxS-PEG NPs showed 98.5% tumor elimination. Our study emphasizes the great potential of CuxS-PEG NPs as an all-in-one NIR-II light-responsive NDDS for applications in biomedicine.

[Varieties and standards of Corydalis medicinal plants].

Through literature research and standard retrieval, Corydalis-derived medicinal materials, the origins, and related standards were summarized. Finally, 27 medicinal materials were screened out, involving 71 species(varieties). Among them, only 11 are recorded in Chinese Pharmacopoeia(2020), National Standard for Chinese Patent Drugs·Tibetan Medicine, Tibetan Medicine Standards, and other local standards, including Corydalis Bungeanae Herba and Corydalis Herba. The names and original plants of the medicinal materials are different in different standards, and the phenomena of "same medicinal material with different names" and "same name for different medicinal materials" are prominent. Most standards only include the traits, microscopic identification, and physico-chemical property identification, with unsound quality criteria. Thus, efforts should be made to strengthen the sorting of Corydalis medicinal plants, herbal textual research, and investigation of the resources and utilization. Moreover, via modern techniques, the chemical components and medicinal material basis of different original plants should be explored and sound quality standards should be established to improve the safety and quality of Corydalis-derived medicinal materials. Summarizing Corydalis medicinal plants, Corydalis-derived medicinal materials, and related standards, this study is expected to provide a reference for the standard formulation, quality evaluation, expansion of drug sources, and rational development and utilization of Corydalis resources.

Mechanism of hyperproteinemia-induced blood cell homeostasis imbalance in an animal model.

Hyperproteinemia is a metabolic disorder associated with increased plasma protein concentration (PPC) and is often clinically complicated by malignant diseases or severe infections. At present, however, research on the molecular mechanism underlying high PPC (HPPC) is scant. Here, an animal model of primary hyperproteinemia was constructed in an invertebrate ( Bombyx mori) to investigate the effects of HPPC on circulating blood cells. Results showed that HPPC affected blood cell homeostasis, leading to increased reactive oxygen species levels, and induced programmed cell death dependent on the endoplasmic reticulum-calcium ion signaling pathway. HPPC induced the proliferation of blood cells, mainly granulocytes, by activating the Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway. Supplementation with the endocrine hormone active substance 20E significantly reduced the impact of HPPC on blood cell homeostasis. Thus, we identified a novel signaling pathway by which HPPC affects blood cell homeostasis, which differs from hyperglycemia, hyperlipidemia, and hypercholesterolemia. In addition, we showed that down-regulation of gene expression of the hematopoietic factor Gcm could be used as a potential early detection indicator for hyperproteinemia.

Baseline Volumetric T2 Relaxation Time Histogram Analysis: Can It Be Used to Predict the Response to Intravenous Methylprednisolone Therapy in Patients With Thyroid-Associated Ophthalmopathy?

Objective: Prediction of therapy response to intravenous methylprednisolone pulses (ivMP) is crucial for thyroid-associated ophthalmopathy (TAO). Image histograms may offer sensitive imaging biomarkers for therapy effect prediction. This study aimed to investigate whether pretherapeutic, multiparametric T2 relaxation time(T2RT) histogram features of extraocular muscles (EOMs) can be used to predict therapy response. Materials and Methods: Forty-five active and moderate-severe TAO patients, who were treated with standard ivMP and underwent orbital MRI before therapy, were retrospectively included in this study. The patients were divided into responsive (n = 24, 48 eyes) and unresponsive group(n = 21, 42 eyes) according to clinical evaluation. Baseline clinical features of patients and histogram-derived T2RT parameters of the EOMs were analyzed and compared. Logistic regression model was conducted to determine independent predictors, and a histogram features nomogram was formulated for personalized prediction. Results: Responsive group displayed lower values for 5th, 10th percentiles (P < 0.050, respectively), and higher values for 75th, 90th, and 95th percentiles, skewness, entropy, and inhomogeneity (P < 0.050, respectively) than unresponsive group. Multivariate logistic regression analysis showed that 95th percentile of >88.1 [odds ratio (OR) = 12.078; 95% confidence interval (CI) = 3.98-36.655, p < 0.001], skewness of >0.31 (OR = 3.935; 95% CI = 2.28-6.788, p < 0.001) and entropy of >3.41 (OR = 4.375; 95% CI = 2.604-7.351, p < 0.001) were independent predictors for favorable response. The nomogram integration of three independent predictors demonstrated optimal predictive efficiency, with a C-index of 0.792. Conclusions: Pre-treatment volumetric T2RT histogram features of EOMs could function to predict the response to ivMP in patients with TAO. The nomogram based on histogram features facilitates the selection of patients who will derive maximal benefit from ivMP.

Therapeutic effect of berberine on metabolic diseases: Both pharmacological data and clinical evidence.

The increased incidence of metabolic diseases (e.g., diabetes and obesity) has seriously affected human health and life safety worldwide. It is of great significance to find effective drugs from natural compounds to treat metabolic diseases. Berberine (BBR), an important quaternary benzylisoquinoline alkaloid, exists in many traditional medicinal plants. In recent years, BBR has received widespread attention due to its good potential in the treatment of metabolic diseases. In order to promote the basic research and clinical application of BBR, this review provides a timely and comprehensive summary of the pharmacological and clinical advances of BBR in the treatment of five metabolic diseases, including type 2 diabetes mellitus, obesity, non-alcoholic fatty liver disease, hyperlipidemia, and gout. Both animal and clinical studies have proved that BBR has good therapeutic effects on these five metabolic diseases. The therapeutic effects of BBR are based on regulating various metabolic aspects and pathophysiological procedures. For example, it can promote insulin secretion, improve insulin resistance, inhibit lipogenesis, alleviate adipose tissue fibrosis, reduce hepatic steatosis, and improve gut microbiota disorders. Collectively, BBR may be a good and promising drug candidate for the treatment of metabolic diseases. More studies, especially clinical trials, are needed to further confirm its molecular mechanisms and targets. In addition, large-scale, long-term and multi-center clinical trials are necessary to evaluate the efficacy and safety of BBR in the treatment of these metabolic diseases.

Elucidation of the active ingredients of Lamiophlomis herba against hemorrhage based on network pharmacology and tail snipping model in mice.

This study aimed to elucidate the active ingredients of Lamiophlomis herba (LH), the overground part of Lamiophlomis rotata (Benth.) Kudo, against hemorrhage based on network pharmacology and tail snipping model in mice. A total of 118 hemorrhage-related target genes were identified by retrieving public databases, and 39 genes were identified as the hub genes of hemorrhage based on protein-protein interaction and module analyses. The interactions between 67 potentially active ingredients in LH and 7 genes in the 39 hub genes were established and analyzed through molecular docking and Cytoscape. A total of 21 ingredients were involved in the interactions, and were divided into three categories: iridoid (15 ingredients), flavonoid (2 ingredients) and other category (4 ingredients). Based on the "multi-ingredient, multi-target" characteristic of traditional Chinese medicines (TCMs), the results of network pharmacology indicated that iridoid might be the key active ingredient group of LH against hemorrhage. The contribution of iridoid to the hemostatic effect of LH was investigated by the tail snipping model in mice. The results showed that iridoid was the key active ingredient group of LH against hemorrhage, which confirmed the prediction in network pharmacology. Additionally, the previous reports also supported this prediction. In conclusion, the finding of the present study indicates that iridoid is the key hemostatic ingredient group of LH. This work provides valuable references for investigation of the hemostatic ingredients of LH based on the holistic theory of TCMs. Meanwhile, this work also provides further insight into the development of hemostatic drugs based on LH.

Nanoplatforms with Remarkably Enhanced Absorption in the Second Biological Window for Effective Tumor Thermoradiotherapy.

Thermoradiotherapy acts as an important antitumor modality because heating can increase the blood flow and improve the oxygen level in tumor, thus remission of hypoxia-associated resistance for radiotherapy (RT). However, most agents for thermoradiotherapy are used either in the first near-infrared biological window or low photothermal conversion efficiency. Here, a facile method to prepare CuxS/Au nanocomposites via reduction methods from CuxS templates in mild synthetic conditions (i.e., aqueous solution and room temperature) is presented. After the growth of Au nanoparticles, the CuxS/Au nanocomposites have greater benefits for photothermal efficiency than that of CuxS nanoparticles due to the enhanced absorbance in the second near-infrared window. Moreover, biocompatibility and stability of these nanocomposites are greatly improved by lipoic acid poly(ethylene glycol). After the tumors were irradiated with a 1064 nm laser, their oxygenation status is subsequently improved, and the combination of photothermal therapy and RT achieves remarkable synergistic therapeutic effects. This work provides a novel idea to design a new-generation nanomedicine for tumor thermoradiotherapy.

[Research on contents of anthraquinones,dianthrones and tannins in Rheum tanguticum on PCA and CA].

Anthraquinones,dianthrones and tannins are the main active ingredients of Rheum tanguticum. In this study the three components were determined by HPLC,and the results were analyzed by multiple comparisons,principal components analysis(PCA)and correspondence analysis(CA). The results showed that the contents of components in different growing areas and types(wild and cultivated) reached a significant level(P<0. 05). Baiyu county,Xiaojin county and Ruoergai county had obvious advantages in the accumulation of catechin hydrate,rhien and sensenoside A respectively. The principal component was different in two growing type and the wild environment was conducive to combined anthraquinones accumulation. For active components,normalized planting was better than retail cultivating. Therefore,the effect on the accumulation of chemical components in Rh. tangusticum,should be taken into full account in the selection of the cultural base of Rh. tanguticum. The standardized cultivating is superior to retail cultivating in terms of the accumulation of active ingredients,and standardized planting is inferior to the wild.

Chinese Herbal Cardiotonic Pill Stabilizes Vulnerable Plaques in Rabbits by Decreasing the Expression of Adhesion Molecules.

The cardiotonic pill (CP), consisting of a mixture of Radix Salviae Miltiorrhizae, Radix Notoginseng, and Borneolum Syntheticum, has been widely used in the prevention and treatment of cardiovascular disease. Adhesion molecules, including intercellular cell adhesion molecule-1 and vascular cell adhesion molecule-1, are involved in the development of vulnerable plaque. We investigated the effect of the CP in a rabbit model of vulnerable plaque established by local transfection with p53 gene. Compared with the control group, rabbits with vulnerable plaque showed a significantly lower intima-media thickness and plaque burden after CP treatment for 12 weeks. Moreover, the reduction in rate of plaque rupture and vulnerability index was similar. On enzyme-linked immunosorbent assay, real-time polymerase chain reaction, and immunohistochemistry analysis, the expression of intercellular cell adhesion molecule-1 and vascular cell adhesion molecule-1 was inhibited with CP treatment. CP treatment could postpone atherosclerotic plaque development and stabilize vulnerable plaque by inhibiting the expression of adhesion molecules in treatment of cardiovascular disease.

[Effect of spring topdressing on yield, ferulic acid and total alkaloids of Ligusticum chuanxiong].

A field trial was carried out to study the influence of different kinds of spring topdressing on growth, yield and quality of Ligusticum chuanxiong. The results showed that the spring topdressing had effects of improving root length, tiller numbers and plant height to some extent. At the same time the chlorophyll content and dry weight accumulation especially the dry weight of root increased significantly. It also showed that the yield increased and quality was improved significantly. The effect of different treatment with urea58.7 kg x hm(-2)(N 27 kg x hm(-2)) was the best and the treatment with N,P,K the second.

[Study of Rhizoma chuanxiong storage conditions].

OBJECTIVE: To study the different packing and storage life effect on the content of effective element in Rhizoma Chuanxiong, so as to guide the packing, moist, volatile oil and ferulic acid in Rhizoma Chuanxiong from two GAP base by the related determination method in supplyment of China Pharmocopeia (2000). And the content of total alkaloids was determined by acid dye colorimentry. RESULTS: The loss of effective element in Rhizoma Chuanxiong was the least when in vaccum packing, sack and weave packet. During the storage the content of moist and volatile oil decreased; the content of ferulic acid increased;the content variety of total alkaloids had no regulation. CONCLUSION: We should choose the sack and weave packet as the packing of Rhizoma Chuanxiong. If the quantity is small we should use vaccum packing. Conbined the changes of Rhizoma Chuanxiong effective element and the phenomenon of mildew and worm eaten during storage, we should not store it for long time.

[Determination of coumarins content in Radix Angelicae dahuricae by HPLC and UV].

OBJECTIVE: To determine the coumarins content in Radix Angelicae Dahuricae (Baizhi). METHODS: The total content of coumarins was determined by UV. The content of imperatorin, isoimperatorin and oxypeucedanin hydrate in different samples was carriedut by HPLC. RESULTS: The processing method and the medicinal position have great effect on the coumarin content. CONCLUSION: The content of oxypeucedanin hydrate in Baizhi was determined. This method can be used for quality control of Baizhi.