Total iridoid glycoside extract of Lamiophlomis rotata (Benth) Kudo accelerates diabetic wound healing by the NRF2/COX2 axis.

BACKGROUND: Lamiophlomis rotata (Benth.) Kudo (L. rotata), the oral Traditional Tibetan herbal medicine, is adopted for treating knife and gun wounds for a long time. As previously demonstrated, total iridoid glycoside extract of L. rotata (IGLR) induced polarization of M2 macrophage to speed up wound healing. In diabetic wounds, high levels inflammatory and chemotactic factors are usually related to high reactive oxygen species (ROS) levels. As a ROS target gene, nuclear factor erythroid 2-related factor 2 (NRF2), influences the differentiation of monocytes to M1/M2 macrophages. Fortunately, iridoid glycosides are naturally occurring active compounds that can be used as the oxygen radical scavenger. Nevertheless, the influence of IGLR in diabetic wound healing and its associated mechanism is largely unclear. MATERIALS AND METHODS: With macrophages and dermal fibroblasts in vitro, as well as a thickness excision model of db/db mouse in vivo, the role of IGLR in diabetic wound healing and the probable mechanism of the action were investigated. RESULTS: Our results showed that IGLR suppressed oxidative distress and inflammation partly through the NRF2/cyclooxygenase2 (COX2) signaling pathway in vitro. The intercellular communication between macrophages and dermal fibroblasts was investigated by the conditioned medium (CM) of IGLR treatment cells. The CM increased the transcription and translation of collagen I (COL1A1) and alpha smooth muscle actin (α-SMA) within fibroblasts. With diabetic wound mice, the data demonstrated IGLR activated the NRF2/KEAP1 signaling and the downstream targets of the pathway, inhibited COX2/PEG2 signaling and decreased the interaction inflammatory targets of the axis, like interleukin-1beta (IL-1ß), interleukin 6 (IL-6), apoptosis-associated speck-like protein (ASC), cysteinyl aspartate specific proteinase1 (caspase1) and NOD-like receptor-containing protein 3 (NLRP3).In addition, the deposition of COL1A1, and the level of α-SMA, and Transforming growth factor-ß1 (TGF-ß1) obviously elevated, whereas that of pro-inflammatory factors reduced in the diabetic wound tissue with IGLR treatment. CONCLUSION: IGLR suppressed oxidative distress and inflammation mainly through NRF2/COX2 axis, thus promoting paracrine and accelerating wound healing in diabetes mice.

Targeted Cyclo[8]pyrrole-Based NIR-II Photoacoustic Tomography Probe for Suppression of Orthotopic Pancreatic Tumor Growth and Intra-abdominal Metastases.

Pancreatic cancer is highly lethal. New diagnostic and treatment modalities are desperately needed. We report here that an expanded porphyrin, cyclo[8]pyrrole (CP), with a high extinction coefficient (89.16 L/g·cm) within the second near-infrared window (NIR-II), may be formulated with an αvß3-specific targeting peptide, cyclic-Arg-Gly-Asp (cRGD), to form cRGD-CP nanoparticles (cRGD-CPNPs) with promising NIR-II photothermal (PT) therapeutic and photoacoustic (PA) imaging properties. Studies with a ring-array PA tomography system, coupled with analysis of control nanoparticles lacking a targeting element (CPNPs), revealed that cRGD conjugation promoted the delivery of the NPs through abnormal vessels around the tumor to the solid tumor core. This proved true in both subcutaneous and orthotopic pancreatic tumor mice models, as confirmed by immunofluorescent studies. In combination with NIR-II laser photoirradiation, the cRGD-CPNPs provided near-baseline tumor growth inhibition through PTT both in vitro and in vivo. Notably, the combination of the present cRGD-CPNPs and photoirradiation was found to inhibit intra-abdominal metastases in an orthotopic pancreatic tumor mouse model. The cRGD-CPNPs also displayed good biosafety profiles, as inferred from PA tomography, blood analyses, and H&E staining. They thus appear promising for use in combined PA imaging and PT therapeutic treatment of pancreatic cancer.

Iodine Adsorption-Desorption-Induced Structural Transformation and Improved Ag+ Turn-On Luminescent Sensing Performance of a Nonporous Eu(III) Metal-Organic Framework.

Posttreatment of pristine metal-organic frameworks (MOFs) with suitable vapor may be an effective way to regulate their structures and properties but has been less explored. Herein, we report an interesting example in which a crystalline nonporous Eu(III)-MOF was transferred to a porous amorphous MOF (aMOF) via iodine vapor adsorption-desorption posttreatment, and the resulting aMOF showed improved turn-on sensing properties with respect to Ag+ ions. The crystalline Eu-MOF, namely, Eu-IPDA, was assembled from Eu(III) and 4,4'-{4-[4-(1H-imidazol-1-yl)phenyl]pyridine-2,6-diyl}dibenzoic acid (H2IPDA) and exhibited a two-dimensional (2D) coordination network based on one-dimensional secondary building blocks. The close packing of the 2D networks gives rise to a three-dimensional supramolecular framework without any significant pores. Interestingly, the nonporous Eu-IPDA could absorb iodine molecules when Eu-IPDA crystals were placed in iodine vapor at 85 °C, and the adsorption capacity was 1.90 g/g, which is comparable to those of many MOFs with large BET surfaces. The adsorption of iodine is attributed to the strong interactions among the iodine molecule, the carboxy group, and the N-containing group and leads to the amorphization of the framework. After immersion of the iodine-loaded Eu-IPDA in EtOH, approximately 89.7% of the iodine was removed, resulting in a porous amorphous MOF, denoted as a-Eu-IPDA. In addition, the remaining iodine in the a-Eu-IPDA framework causes strong luminescent quenching in the fluorescence emission region of the Eu(III) center when compared with that in Eu-IPDA. The luminescence intensity of a-Eu-IPDA in water suspensions was significantly enhanced when Ag+ ions were added, with a detection limit of 4.76 × 10-6 M, which is 1000 times that of pristine Eu-IPDA. It also showed strong anti-interference ability over many common competitive metal ions and has the potential to sense Ag+ in natural water bodies and traditional Chinese medicine preparations. A mechanistic study showed that the interactions between Ag+ and the absorbed iodine, the carboxylate group, and the N atoms all contribute to the sensing performance of a-Eu-IPDA.

Transcriptomic and proteomic investigation of the ameliorative effect of total polyphenolic glycoside extract on hepatic fibrosis in Lamiophlomis rotata Kudo via the AGE/RAGE pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: During the regression of liver fibrosis, a decrease in hepatic stellate cells (HSCs) can occur through apoptosis or inactivation of activated HSCs (aHSCs). A new approach for antifibrotic therapy involves transforming hepatic myofibroblasts into a quiescent-like state. Lamiophlomis rotata (Benth.) Kudo (L. rotata), an orally available Tibetan herb, has traditionally been used to treat skin disease, jaundice, and rheumatism. In our previous study, we found that the total polyphenolic glycoside extract of L. rotata (TPLR) promotes apoptosis in aHSCs for the treatment of hepatic fibrosis. However, whether TPLR induces aHSCs to become inactivated HSCs (iHSCs) is unclear, and the underlying mechanism remains largely unknown. PURPOSE: This study aimed to examine the impact of TPLR on the phenotypes of hepatic stellate cells (HSCs) during the regression of liver fibrosis and explore the potential mechanism of action. METHODS: The effect of TPLR on the phenotypes of hepatic stellate cells (HSCs) was assessed using immunofluorescence (IF) staining, reverse transcription-polymerase chain reaction (RT-PCR), and Western blotting. Transcriptomic and proteomic methods were employed to identify the main signaling pathways involved. Based on the omics results, the likely mechanism of TPLR on the phenotypes of aHSCs was confirmed through overexpression and knockdown experiments in TGF-ß1-activated LX-2 cells. Using a CCl4-induced liver fibrosis mouse model, we evaluated the anti-hepatic fibrosis effect of TPLR and explored its potential mechanism based on omics findings. RESULTS: TPLR was found to induce the differentiation of aHSCs into iHSCs by significantly decreasing the protein expression of α-SMA and Desmin. Transcriptomic and proteomic analyses revealed that the AGE/RAGE signaling pathway plays a crucial role in the morphological transformation of HSCs following TPLR treatment. In vitro experiments using RAGE overexpression and knockdown demonstrated that the mechanism by which TPLR affects the phenotype of HSCs is closely associated with the RAGE/RAS/MAPK/NF-κB axis. In a model of liver fibrosis, TPLR obviously inhibited the generation of AGEs and alleviated liver tissue damage and fibrosis by downregulating RAGE and its downstream targets. CONCLUSION: The AGE/RAGE axis plays a pivotal role in the transformation of activated hepatic stellate cells (aHSCs) into inactivated hepatic stellate cells (iHSCs) following TPLR treatment, indicating the potential of TPLR as a therapeutic agent for the management of liver fibrosis.

CTNNB1 p.D32A (c.95A > C) somatic mutation in stage I grade 1 endometrioid endometrial carcinoma with lung metastasis: a case report.

BACKGROUND: Most endometrial cancers are of low histological grade and uterine-confined, with a high 5-year survival rate. However, a small subset of women with low-grade and early-stage endometrioid endometrial cancer experience recurrence and death; thus, a more precise risk-stratification is needed. CASE PRESENTATION: A 29-year-old woman presented with abnormal vaginal bleeding and was diagnosed with FIGO grade 1 endometrioid endometrial carcinoma by curettage. Comprehensive cancer staging including pelvic and para-aortic lymphadenectomy was then performed. Postoperative pathological findings suggested an FIGO grade 1 endometrioid endometrial carcinoma infiltrating the superficial muscle layer. The patient did not receive adjuvant therapy. After 4 years of follow-up, the patient returned to our institution with lung metastasis. She underwent thoracoscopic resection of the affected lobes, followed by six cycles of combined chemotherapy of paclitaxel and carboplatin. Next-generation sequencing showed that the primary and lung metastatic tumors shared 4 mutations: PTEN (p.P248Lfs*8), CTNNB1 (p.D32A), BCOR (p.N1425S) and CBL (p.S439N). Immunohistochemistry revealed nuclear location of ß-catenin in the primary and lung metastatic tumor samples, indicating abnormal activation of ß-catenin. CONCLUSION: CTNNB1p.D32A (c.95A > C) mutation may be related to lung metastasis in this patient with low-grade early-stage endometrioid endometrial carcinoma.

Inhibition of Pro-Survival Autophagy Induced by Rare-Earth Nanocomposites for Promoting Photothermal Therapy of Visualized Tumors.

Manipulation of autophagic processes has emerged as a promising strategy for synergizing nanoagent-mediated photothermal therapy (PTT). Most of the current studies focus on improving PTT efficacy by inhibiting pro-survival autophagy induced by the heat generated from the photothermal process. However, autophagy induced by the nanoagents is usually ignored, which may weaken the effect of autophagy-mediated efficacy improvement in PTT if induced autophagy is pro-death. Therefore, this work aims at developing a nanoagent that is able to induce heat-synergetic pro-survival autophagy to optimize the efficacy of PTT. An approach is developed to coat carbon layer, polyethylenimine (PEI), and folic acid (FA) on NaYF4 :Er,Yb,Nd@NaNdF4 (DCNPs@C@PEI@FA, DCPF) nanoparticles successively, giving access to the nanoagent to induce pro-survival autophagy. The synthetic imaging-guided photothermal nanoagent displays outstanding targeting ability and biocompatibility based on the surface modification of PEI and FA. By using an autophagy inhibitor chloroquine, a conspicuously synergistic effect on DCPF-mediated PTT in vitro and in vivo tumor models (HeLa) is achieved. A promising strategy is presented here to enhance the efficacy of imaging-guided PTT by modulating the autophagy induced by the nanoagent.

Effect of Shugan Tiaoshen acupuncture combined with western medication on depression-insomnia comorbidity due to COVID-19 quarantine: a multi-central randomized controlled trial / 中国针灸

OBJECTIVE@#To observe the effect of Shugan Tiaoshen acupuncture (acupuncture for soothing the liver and regulating the mentality) combined with western medication on depression and sleep quality in the patients with depression-insomnia comorbidity due to COVID-19 quarantine, and investigate the potential mechanism from the perspective of cortical excitability.@*METHODS@#Sixty patients with depression-insomnia comorbidity due to COVID-19 quarantine were randomly divided into an acupuncture group and a sham-acupuncture group, 30 cases in each one. The patients of both groups were treated with oral administration of sertraline hydrochloride tablets. In the acupuncture group, Shugan Tiaoshen acupuncture was supplemented. Body acupuncture was applied to Yintang (GV 24+), Baihui (GV 20), Hegu (LI 4), Zhaohai (KI 6), Qihai (CV 6), etc. The intradermal needling was used at Xin (CO15), Gan (CO12) and Shen (CO10). In the sham-acupuncture group, the sham-acupuncture was given at the same points as the acupuncture group. The compensatory treatment was provided at the end of follow-up for the patients in the sham-acupuncture group. In both groups, the treatment was given once every two days, 3 times a week, for consecutive 8 weeks. The self-rating depression scale (SDS) and insomnia severity index (ISI) scores were compared between the two groups before and after treatment and 1 month after the end of treatment (follow-up) separately. The cortical excitability indexes (resting motor threshold [rMT], motor evoked potential amplitude [MEP-A], cortical resting period [CSP]) and the level of serum 5-hydroxytryptamine (5-HT) were measured before and after treatment in the two groups.@*RESULTS@#After treatment and in follow-up, SDS and ISI scores were decreased in both groups compared with those before treatment (P<0.05), and the scores in the acupuncture group were lower than those in the sham-acupuncture group (P<0.05), and the decrease range in the acupuncture group after treatment was larger than that in the sham-acupuncture group (P<0.05). After treatment, rMT was reduced (P<0.05), while MEP-A and CSP were increased (P<0.05) in the acupuncture group compared with that before treatment. The levels of serum 5-HT in both groups were increased compared with those before treatment (P<0.05). The rMT in the acupuncture group was lower than that in the sham-acupuncture group, while MEP-A and CSP, as well as the level of serum 5-HT were higher in the acupuncture group in comparison with the sham-acupuncture group (P<0.05).@*CONCLUSION@#Shugan Tiaoshen acupuncture combined with western medication can relieve depression and improve sleep quality in the patients with depression-insomnia comorbidity due to COVID-19 quarantine, which is probably related to rectifying the imbalanced excitatory and inhibitory neuronal functions.

Hemiepiphytic figs kill their host trees: acquiring phosphorus is a driving factor.

Hemiepiphytic figs killing their host trees is an ecological process unique to the tropics. Yet the benefits and adaptive strategies of their special life history remain poorly understood. We compared leaf phosphorus (P) content data of figs and palms worldwide, and functional traits and substrate P content of hemiepiphytic figs (Ficus tinctoria), their host palm and nonhemiepiphytic conspecifics at different growth stages in a common garden. We found that leaf P content of hemiepiphytic figs and their host palms significantly decreased when they were competing for soil resources, but that of hemiepiphytic figs recovered after host death. P availability in the canopy humus and soil decreased significantly with the growth of hemiepiphytic figs. Functional trait trade-offs of hemiepiphytic figs enabled them to adapt to the P shortage while competing with their hosts. From the common garden to a global scale, the P competition caused by high P demand of figs may be a general phenomenon. Our results suggest that P competition is an important factor causing host death, except for mechanically damaging and shading hosts. Killing hosts benefits hemiepiphytic figs by reducing interspecific P competition and better acquiring P resources in the P-deficient tropics, thereby linking the life history strategy of hemiepiphytic figs to the widespread P shortage in tropical soils.

Dedicated Photoacoustic Imaging Instrument for Human Periphery Blood Vessels: A New Paradigm for Understanding the Vascular Health.

A novel photoacoustic imaging system based on a semi-ring transducer array is proposed to image peripheral blood vessels. The system's penetration depth is deep (∼15 mm) with high spatial (∼200 µm) and temporal resolution. In a clinical study, volumetric photoacoustic data of limbs were obtained within the 50s (for a FOV of 15 cm × 4 cm) with the volunteers in the standing and sitting posture. Compared to the previous studies, our system has many advantages, including (1) Larger field of view; (2) Finer elevational and in-plane resolutions; (3) Enhanced 3D visualization of peripheral vascular networks; (4) Compact size and better portability. The 3D visualization and cross-sectional images of five healthy volunteers clearly show the vascular network and the system's ability to image submillimeter blood vessels. This high-resolution PA system has great potential for imaging human periphery vasculatures noninvasively in clinical research.

[Research progress in original species identification in industry chain of Rhei Radix et Rhizoma].

Rhei Radix et Rhizoma is a kind of commonly used Chinese medicinal materials. Due to the overharvesting, the wild resource is endangering. Large market demand caused severely adulterant of commercial Rhei Radix et Rhizoma medicinal materials and decoction pieces. This manuscript reviewed the advances of the original species authentication in the industrial chain of Rhei Radix et Rhizoma during the latest decade, including characteristics and microscopic features, phytochemical analysis on anthraquinones, and molecular authentication based on DNA barcoding. Accordingly, an original species authentication route for the industrial chain of Rhei Radix et Rhizoma was summarized:(1)the identification of seeds and seedlings by DNA barcoding;(2) the selection of high variable sites based on the chloroplast genome;(3)biomonitoring of the Rhei Radix et Rhizoma medicinal materials and decoction pieces by two-dimensional DNA barcode;(4)traceability of Chinese patent medicines by third-generation sequencing. In conclusion, the combination of molecular identification and traditional identification methods provides a new idea for the identification of the original species of Rhei Radix et Rhizoma in the industrial chain and a essential guidance for the research of drug safety and efficacy of Rhei Radix et Rhizoma.

Electroacupuncture at / 中国针灸

OBJECTIVE@#To evaluate the clinical therapeutic effect of electroacupuncture (EA) at @*METHODS@#The data of 318 patients undergoing anal fistula surgery were analyzed retrospectively. In accordance with whether accepted the combined treatment with EA at bilateral @*RESULTS@#For VAS score, there was an interaction between therapeutic method and treatment duration (@*CONCLUSION@#Electroacupuncture at

Ethnobotanical study on wild edible plants used by three trans-boundary ethnic groups in Jiangcheng County, Pu'er, Southwest China.

BACKGROUND: Dai, Hani, and Yao people, in the trans-boundary region between China, Laos, and Vietnam, have gathered plentiful traditional knowledge about wild edible plants during their long history of understanding and using natural resources. The ecologically rich environment and the multi-ethnic integration provide a valuable foundation and driving force for high biodiversity and cultural diversity in this region. However, little study has uncovered this unique and attractive culture to the world. METHODS: We conducted ethnobotanical survey in 20 villages of Jiangcheng County from 2016 to 2020. Altogether 109 local Dai, Hani, and Yao people were interviewed, and their traditional knowledge about wild edible plants was recorded. Voucher specimens were identified by the authors and deposited in the herbarium of Xishuangbanna Tropical Botanical Garden, Chinese Academy of Sciences (HITBC). The use value was used as a quantitative index to evaluate the consumption frequency and relative importance of the wild edible plants. The Jaccard index was calculated to assess the usage similarity of different areas. The relationship of age and recognized wild edible plants by different ethnic people was performed by R. RESULTS: A total of 211 wild edible plants, belonging to 71 families and 151 genera, were recorded. These plants were consumed as wild edible vegetables, seasonal fruits, salads, spices, sour condiments, tonic soups, tea substitutes, liquor brewing, or dyeing materials. The use value (UV), current cultivation, market availability, and the quantitative traditional knowledge inheritance situation of these wild edible plants among different generations, were analyzed. Based on the data from the threatened species list of China's higher plants and the IUCN Red List, the food plant list for Asia Elephant, the Subject Database of China Plant, and the calculated UV score, the top 30 most important wild edible plants were selected for further cultivation in some local villages. CONCLUSION: Traditional knowledge of wild edible plants, owned by Dai, Hani, and Yao people in Jiangcheng County, is rich but at risk of being lost among the young generation. Diversified cultivation of wild edible plants by the local communities could be a solution for the sustainable use of natural resources and to conserve the endangered species in this trans-boundary region.

Effects of human disturbance activities and environmental change factors on terrestrial nitrogen fixation.

Biological nitrogen (N) fixation plays an important role in terrestrial N cycling and represents a key driver of terrestrial net primary productivity (NPP). Despite the importance of N fixation in terrestrial ecosystems, our knowledge regarding the controls on terrestrial N fixation remains poor. Here, we conducted a meta-analysis (based on 852 observations from 158 studies) of N fixation across three types of ecosystems with different status of disturbance (no management, restoration [previously disturbed], and disturbance [currently disturbed]) and in response to multiple environmental change factors (warming, elevated carbon dioxide [CO2 ], increased precipitation, increased drought, increased N deposition, and their combinations). We explored the mechanisms underlying the changes in N fixation by examining the variations in soil physicochemical properties (bulk density, texture, moisture, and pH), plant and microbial characteristics (dominant plant species numbers, plant coverage, and soil microbial biomass), and soil resources (total carbon, total N, total phosphorus (P), inorganic N, and inorganic P). Human disturbance inhibited non-symbiotic N fixation but not symbiotic N fixation. Terrestrial N fixation was stimulated by warming (+152.7%), elevated CO2 (+19.6%), and increased precipitation (+73.1%) but inhibited by increased drought (-30.4%), N deposition (-31.0%), and combinations of available multiple environmental change factors (-14.5%), the extents of which varied among biomes and ecosystem compartments. Human disturbance reduced the N fixation responses to environmental change factors, which was associated with the changes in soil physicochemical properties (2%-56%, p < .001) and the declines in plant and microbial characteristics (3%-49%, p ≤ .003) and soil resources (6%-48%, p ≤ .03). Overall, our findings reveal for the first time the effects of multiple environmental change factors on terrestrial N fixation and indicate the role of human disturbance activities in inhibiting N fixation, which can improve our understanding, modeling, and prediction of terrestrial N budgets, NPP, and ecosystem feedbacks under global change scenarios.

Improving oxidative stability and release behavior of docosahexaenoic acid algae oil by microencapsulation.

BACKGROUND: Spray-dried docosahexaenoic acid algae oil (DHA AO) microcapsules were prepared using whey protein isolate and glucose syrup (WPI + GS), or sodium starch octenylsuccinate and glucose syrup (SSOS + GS), or whey protein isolate and lactose (WPI + L). The effect of the formulations on encapsulation properties, oxidative protection and in vitro oil release pattern of the resulting microencapsulates was investigated. RESULTS: A high encapsulation efficiency of over 98% of DHA AO was obtained for microcapsules with all three wall materials. Among the wall materials, SSOS + GS exhibited a better micro-particulation ability reflected by more uniform size and smoother surface of the formed microcapsules and no agglomerates. DHA AO microcapsules with all the wall materials showed good protection of the oil from oxidation during storage with an increasing order of WPI + GS, SSOS + GS and WPI + L. Moreover, microencapsulation significantly increased the release of DHA AO in the intestinal phase of the in vitro digestion process with an increasing order of SSOS + GS, WPI + GS and WPI + L, indicating the increased stability of the oil in the highly acidic gastric environment and the enhanced lipid digestibility in the small intestine. CONCLUSIONS: The results suggest that it is possible to transform a highly oxidizable liquid functional food ingredient such as DHA AO into a stable and easy-to-handle solid powder through spray drying with properly selected wall materials. © 2020 Society of Chemical Industry.

Isolation and identification of zinc-chelating peptides from sea cucumber (Stichopus japonicus) protein hydrolysate.

BACKGROUND: Zinc is known to play an essential role in the biological activities in the human body. In this study, a zinc-chelating peptide (ZCP) produced by Alcalase-assisted hydrolysis of the body wall of sea cucumber was isolated and identified. The ZCP was purified stepwise by ultrafiltration, anion-exchange chromatography, and gel filtration chromatography, in conjunction with ultraviolet-visual (UV-visual) spectrophotometry, which was used to analyze each purified fraction. RESULTS: Analysis of the purified ZCP revealed that its zinc-chelating ability was 33.31%. Analysis of isothermal titration calorimetry suggested that the binding of ZCP and zinc (N ≈ 2) was endothermic, with weak binding affinity. Fourier transform infrared spectroscopy spectra (FTIR) indicated that carboxylic and amide groups in ZCP were the primary binding sites of Zn. Sequencing the result by ultra-performance liquid chromatography-quadrupole/time of flight mass spectrometry (UPLC-Q-TOF-MS/MS) showed that a representative ZCP had the sequence WLTPTYPE with a molecular weight of 1005.5 Da. CONCLUSION: These results provide a promising foundation for the production of zinc supplements from sea-cucumber-derived ZCPs. © 2019 Society of Chemical Industry.

Novel small molecular dye-loaded lipid nanoparticles with efficient near-infrared-II absorption for photoacoustic imaging and photothermal therapy of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the most common malignant cancers worldwide and is the second leading cause of mortality in cancer patients. Thus, accurate diagnosis and effective treatment of the malignancy is very critical for HCC patients. The photoacoustic (PA) nanoparticle with ultra-sensitive imaging signals and high photothermal conversion efficacy is a new and promising method for achieving the desired goals. In this study, we have synthesized a novel lipid nanoparticle based on IR-1061 dyes by encapsulating the dye into a liposome which was modified by DSPE-PEG2000. We conducted serial experiments to investigate the PA diagnosis performance, the surgical navigation, and the photothermal therapy (PTT) capability of the novel nanoparticle (Polipo-IR NP) in nude mice bearing HCC. The results showed that our novel nanoparticles exhibited strong laser energy absorption at 1064 nm wavelength, high photothermal conversion efficacy (45.25%) and ultra-sensitive PA signals. The in vivo PA studies demonstrated that the proposed nanoparticles could diagnose tumors non-invasively and accurately with a strong signal-to-noise ratio of 5.98 ± 0.23 at 3 h post-injection and could successfully achieve radical resection of tumors intraoperatively. Furthermore, the PTT test demonstrated a remarkable cancer cell killing ability because of its high photothermal conversion efficacy. The excellent photostability and high biocompatibility were also validated by in vitro and in vivo experiments. Thus, our proposed NIR-II PA and PTT nanoparticles based on the IR-1061 dye would potentially provide novel insights into understanding polymethine dyes in nanomedicine and would greatly benefit early diagnosis and treatment of HCC patients.

Deciphering the Pharmacological Mechanism of the Herb Radix Ophiopogonis in the Treatment of Nasopharyngeal Carcinoma by Integrating iTRAQ-Coupled 2-D LC-MS/MS Analysis and Network Investigation.

The herb Radix Ophiopogonis (RO) has been used effectively to treat nasopharyngeal carcinoma (NPC) as an adjunctive therapy. Due to the complexity of the traditional Chinese herbs, the pharmacological mechanism of RO's action on NPC remains unclear. To address this problem, an integrative approach bridging proteome experiments with bioinformatics prediction was employed. First, differentially expressed protein profile from NPC serum samples was established using isobaric tag for relative and absolute quantification (iTRAQ) coupled 2-D liquid chromatography (LC)-MS/MS analysis. Second, the RO putative targets were predicted using Traditional Chinese Medicines Integrated Database and known therapeutic targets of NPC were collected from Drugbank and OMIM databases. Then, a network between RO putative targets and NPC known therapeutic targets was constructed. Third, based on pathways enrichment analysis, an integrative network was constructed using DAVID and STRING database in order to identify potential candidate targets of RO against NPC. As a result, we identified 13 differentially expressed proteins from clinical experiments compared with the healthy control. And by bioinformatics investigation, 12 putative targets of RO were selected. Upon interactions between experimental and predicted candidate targets, we identified three key candidate targets of RO against NPC: VEGFA, TP53, and HSPA8, by calculating the nodes' topological features. In conclusion, this integrative pharmacology-based analysis revealed the anti-NPC effects of RO might be related to its regulatory impact via the PI3K-AKT signaling pathway, the Wnt signaling pathway, and the cAMP signaling pathway by targeting VEGFA, TP53, and HSPA8. The findings of potential key targets may provide new clues for NPC's treatments with the RO adjunctive therapy.

Professor 's experience for post-stroke dysphagia treated with penetrating-needling and swallowing technique of acupuncture / 中国针灸

Professor 's experience for post-stroke dysphagia treated with penetrating-needling and swallowing technique of acupuncture is summarized in this paper. The key pathogenesis of this disease is dysfunction of organs, impairment of the house of mental activity and dysfunction of meridian sinew. Innovatively, the anatomic structure related to swallowing is divided into three zones. Based on the distributions of heart, kidney and stomach meridians on the neck, three lines are determined. Hence, the theory of "three-zone and three-line" as well as the penetrating-needling and swallowing technique of acupuncture are put forward. In this paper, the theoretic evidences of penetrating-needling and swallowing technique of acupuncture, point selection and manipulation in treatment of post-stroke dysphagia are introduced.

In vitro digestion profile and calcium absorption studies of a sea cucumber ovum derived heptapeptide-calcium complex.

In this study, a novel calcium-binding heptapeptide (NDEELNK) that is released during the trypsin hydrolysis of sea cucumber ovum was identified by peptidomics. The calcium binding mode, in vitro digestion profile and calcium absorption of the NDEELNK-calcium complex were investigated. The NDEELNK peptide could spontaneously bind calcium with a 1 : 1 stoichiometry, and the calcium-binding site might involve the carboxyl oxygen and amino nitrogen atoms of two glutamic acid and one aspartic acid residues in the NDEELNK peptide. The NDEELNK-calcium complex underwent disaggregation and self-aggregation in a mesh of smaller size during simulated gastrointestinal digestion, clarified by dynamic light scattering and confocal laser-scanning microscopy. In addition, the NDEELNK-calcium complex could be conducive to calcium absorption across Caco-2 cell monolayers. The findings from this research suggest possible utilization of hydrolyzed peptides from sea cucumber ovum as dietary supplements to improve calcium absorption.

Hybrid MoSe2-indocyanine green nanosheets as a highly efficient phototheranostic agent for photoacoustic imaging guided photothermal cancer therapy.

Phototheranostic technology based on photoacoustic imaging (PAI) and photothermal therapy (PTT) is emerging as a powerful tool for tumor theranostic applications. For effective tumor eradication, a novel PAI/PTT theranostic nanoagent with an excellent optical absorption and photothermal capability is highly desired. Herein, we present a new PAI/PTT nanohybrid named sMoSe2-ICG NSs by covalently conjugating aminated indocyanine green (ICG) onto a single layer of molybdenum selenide nanosheets (sMoSe2 NSs). We first validate the sMoSe2-ICG NS agent for the PAI and PTT effect in vitro and then use it for highly-sensitive PAI guided highly efficient tumor PTT in vivo. The sMoSe2-ICG NS hybrid possesses several advantages for PAI/PTT applications: (1) the sMoSe2-ICG NSs have strong absorbance in the broad near-infrared (NIR) region, enabling a highly efficient PAI/PTT theranostic effect and the selection of the most widely used excitation wavelength of 808 nm for PTT; (2) the photothermal ability of ICG in sMoSe2-ICG NSs is augmented due to ICG aggregation induced fluorescence quenching and the re-absorbance of ICG fluorescence by sMoSe2 NSs, which further enhances the PAI/PTT theranostic effect. (3) The characteristic absorption peak of sMoSe2-ICG NSs is red-shifted compared to free ICG, resulting in a higher PAI signal-to-noise ratio (SNR) in vivo. Thus, combined with the good stability, high biocompatibility and minimal toxicity properties, the obtained sMoSe2-ICG NSs hybrid has bright prospects for use in future PAI/PTT clinical applications.