A carrier-free nano-drug assembled via π-π stacking interaction for the treatment of osteoarthritis.

Osteoarthritis (OA) is considered to be the most common joint disorder. Exogenous drug intervention is one of the effective means for OA treatment. Clinical applications of numerous drugs are restricted owing to the short retention as well as rapid clearance in the joint cavity. A wide variety of carrier-based nanodrugs have been developed, but additional carriers may bring unexpected side effects or even toxicity. Herein, by exploiting the spontaneous fluorescence of Curcumin, we designed a new carrier-free self-assembly nanomedicine Curcumin (Cur)/icariin (ICA) nanoparticles with adjustable particle size, which is composed of two small-molecule natural drugs assembled via π-π stacking interaction. Experimental results revealed that Cur/ICA NPs endowed with little cytotoxicity, high cellular uptake and sustained drug release, could inhibit secretion of inflammatory cytokines and reduce cartilage degeneration. Moreover, both the in vitro and in vivo experiments showed the NPs exerted superior synergism effects in anti-inflammatory and cartilage protection than either Cur or ICA alone, and self-monitored its retention by autofluorescence. Thus, the new self-assembly nano-drug combining Cur and ICA represents a new strategy for the treatment of osteoarthritis.

Calcium-to-phosphorus releasing ratio affects osteoinductivity and osteoconductivity of calcium phosphate bioceramics in bone tissue engineering.

Calcium phosphate (Ca-P) bioceramics, including hydroxyapatite (HA), biphasic calcium phosphate (BCP), and beta-tricalcium phosphate (ß-TCP), have been widely used in bone reconstruction. Many studies have focused on the osteoconductivity or osteoinductivity of Ca-P bioceramics, but the association between osteoconductivity and osteoinductivity is not well understood. In our study, the osteoconductivity of HA, BCP, and ß-TCP was investigated based on the osteoblastic differentiation in vitro and in situ as well as calvarial defect repair in vivo, and osteoinductivity was evaluated by using pluripotent mesenchymal stem cells (MSCs) in vitro and heterotopic ossification in muscles in vivo. Our results showed that the cell viability, alkaline phosphatase activity, and expression of osteogenesis-related genes, including osteocalcin (Ocn), bone sialoprotein (Bsp), alpha-1 type I collagen (Col1a1), and runt-related transcription factor 2 (Runx2), of osteoblasts each ranked as BCP > ß-TCP > HA, but the alkaline phosphatase activity and expression of osteogenic differentiation genes of MSCs each ranked as ß-TCP > BCP > HA. Calvarial defect implantation of Ca-P bioceramics ranked as BCP > ß-TCP ≥ HA, but intramuscular implantation ranked as ß-TCP ≥ BCP > HA in vivo. Further investigation indicated that osteoconductivity and osteoinductivity are affected by the Ca/P ratio surrounding the Ca-P bioceramics. Thus, manipulating the appropriate calcium-to-phosphorus releasing ratio is a critical factor for determining the osteoinductivity of Ca-P bioceramics in bone tissue engineering.

Mechanism of Baihe Dihuangtang in Treatment of Depression with Yin Deficiency and Internal Heat / 中国实验方剂学杂志

ObjectiveTo establish a traditional Chinese medicine （TCM） syndrome model with yin deficiency and internal heat， discuss the rationality of model evaluation， and analyze differentially expressed genes in multiple dimensions to explore the molecular mechanism-signaling pathways as well as key targets of Baihe Dihuangtang （BHDH） in treating depression with Yin deficiency and internal heat. MethodForty male SD rats were randomly divided into a blank control group，a model group，a fluoxetine group （positive drug），a BHDH group， and a Zhibai Dihuangtang group （positive drug for Yin deficiency and internal heat）. The depression model with Yin deficiency and internal heat was induced by chronic unpredictable mild stress （CUMS）combined with Chinese herbal drugs with warm and heat nature. The model established was comprehensively evaluated by the detection of the basic condition， behavioral performance， and biochemical indicators of rats in each group. The differentially expressed genes were screened out by mRNA sequencing and underwent Gene Ontology（GO） and Kyoto Encyclopedia of Genes and Genomes（KEGG） pathway enrichment analyses. The protein-protein interaction （PPI） network was plotted and key genes were analyzed to explore the underlying mechanism of BHDH in treating depression with Yin deficiency and internal heat. ResultThe comparison of basic conditions， behavioral assays， energy metabolism， endocrine hormones， cytokines， and neurotransmitters showed that the model was properly induced. BHDH could significantly improve depression with Yin deficiency and internal heat by regulating the pathways related to the nervous system， endocrine system， and inflammatory and immune system. The key genes of the PPI network were Fos， Epha8， Npy2r， Htr2c， and Nr4a1. ConclusionUnder the guidance of TCM theories of treatment based on syndrome differentiation and etiology and pathogenesis，this study established a depression model with yin deficiency and internal heat in animals and evaluation system in accordance with the symptoms and signs of emotional diseases， and further confirmed the scientificity of the modeling method and the underlying mechanism of BHDH in interfering with depression with Yin deficiency and internal heat based on the results of mRNA sequencing.

Treatment of Diabetic Depression with Traditional Chinese Medicine：A Review / 中国实验方剂学杂志

Diabetes and depression are both incurable chronic diseases， which are complementary and integrated. They are clinically called diabetic depression. A large number of epidemiological and clinical studies have confirmed that diabetes interacts with depression， leading to complex conditions of diabetic depression， difficult treatment， and poor prognosis. Diabetes and depression are considered two independent diseases in the majority of the existing clinical methods for the treatment of diabetic depression， with many defects such as low efficiency and severe side effects. Traditional Chinese medicine （TCM） treatment of diabetic depression， characterized by multiple targets， multiple pathways， and overall coordination， can adjust the synergy between multiple systems of the body and is advantageous in the treatment of diabetic depression. However， the evaluation of the efficacy of TCM in the treatment of diabetic depression is mostly limited to the improvement of clinical symptoms， the control of blood sugar level， and the score of depression scale， and there is a lack of in-depth research on the mechanism of action. Therefore， many researchers are devoted to exploring the underlying mechanism of TCM in the treatment of diabetes combined with depression. Clarifying the comorbidity mechanism is the key in treating diabetic depression. In this study， we made an introduction according to the mechanism based on the relevant research reports on the treatment of diabetic depression with TCM and summarized its specific mechanisms， including insulin resistance， oxidative stress and inflammation， and nervous system disorder. The interaction between the various mechanisms has further aggravated the complexity of diabetic depression. We have drawn a diagram of the mechanism pathways of diabetic depression in order to provide new ideas for clinical diagnosis and treatment.

Application of "process management and evaluation" in resident standardization training plan in acupuncture-moxibustion department of hospital for postgraduates of non-acupuncture- moxibustion speciality / 中国针灸

The teaching effect of "process management and evaluation" was assessed in resident standardization training plan in acupuncture-moxibustion department of hospital for postgraduates of non-acupuncture-moxibustion speciality. A total of 120 postgraduates of non-acupuncture-moxibustion speciality participating in resident standardization training were randomized into an observation group (60 cases) and a control group (60 cases, 1 case dropped off). In the control group, the conventional training mode was used. In the observation group, the "process management and evaluation" was adopted, in which, the syllabus was refined, various teaching modes were cooperated and the summary was conducted once a week. The training results were evaluated at the end of 1-month shift test and questionnaire was issued in all of the postgraduates of the two groups. In the observation group, the score for theory and the score of each of the items for technical ability, named differentiation and treatment, technical manipulation and physician-patient communication, as well as the total score were all higher than the control group successively (

Accumulation and excretion of zinc and their effects on growth and food utilization of Spodoptera litura (Lepidoptera: Noctuidae).

By exposing larvae of the holometabolous insect Spodoptera litura to the artificial diets supplemented with a range of Zinc (Zn) contents, we investigated Zn ingestion, excretion and accumulation in the insect throughout its life cycle. The effects of Zn stress on the survival, growth and food utilization of S. litura were also determined. Zn concentrations in the body (larvae, pupae, and adults), faeces, exuviates, puparium, eggs increased with the increasing Zn concentrations in the diets, while Zn excretion and accumulation by S. litura in 750 mg/kg Zn treatments was lower than the 600 mg/kg Zn treatment. In the 450 mg/kg Zn treatment, the Zn accumulation in S. litura at different developmental stages differed as follows: larvae > pupa > adult. S. litura ingested Zn via feeding and could excrete most of the Zn via faeces (compared with Zn excretion via exuviates) to reduce its internal Zn accumulation (compared with Zn ingestion). Survival and weight were significantly inhibited, and the prolonged period of development (larvae, pupae) and shortened longevity of adults were found in S. litura exposed to Zn stress greater than 450 mg Zn/kg. In the 150-450 mg/kg Zn treatments, the 6th instar larvae increased their relative consumption rate (RCR) and approximate digestibility (AD) (namely, food eaten) to gain weight, which resulted in greater Zn accumulation in the body. Therefore, below the threshold level (being close to 450 mg/kg Zn), S. litura seemed to have a strong homeostatic adjustment ability (increase the amount of food eaten, thereby increasing AD, RCR and Zn excretion via faeces and exuviates) to sustain their weight, and Zn was beneficial and harmless. Although larvae treated with 750 mg/kg Zn had a similar RCR and AD as the control, a reduced weight gain and prolonged larval period resulted in significantly lower relative growth rate (RGR), which indicated surviving insects may allocate more energy from foods for detoxification than for growth.

Effect of Qingjin Huatantang on AECOPD Inflammatory Factors by Regulating p62 / 中国实验方剂学杂志

Objective:To regulate autophagy protein p62 of airway epithelial cells in acute exacerbation of chronic obstructive pulmonary disease (AECOPD) rats with Qingjin Huatantang, in order to explore its effect on interleukin (IL) -1β and tumor necrosis, tumor necrosis factor-α (TNF-α), leukotriene B4 (LTB4), and leukotriene C4 (LTC4). Method:Airway epithelial cells and AECOPD airway epithelial cells were cultured. Sixty SPF male SD rats were randomly divided into 6 groups, namely high, medium and low-dose Qingjin Huatantang groups, western medicine group, model group and normal group. Except for the normal group, the remaining groups were included into the AECOPD model by lipopolysaccharide (LPS) tracheal instillation method + fumigation method. After modeling, the dosage of the high-dose traditional Chinese medicine group was 30 g·kg-1·d-1, that of the middle-dose group was 15 g·kg-1·d-1, that of the low-dose group was 7.5 g·kg-1·d-1, the positive control group was given luo erythromycin (0.017 5 g·kg-1·d-1), the model group and the blank control group were orally given normal saline with the volume of 20 mL·kg-1·d-1. Serum was extracted two weeks after administration, and the cells were intervened with drug-containing serum. The content of interleukin IL-1β, TNF-α, and LTB4 in cell supernatants were detected by enzyme-linked immunosorbent assay (ELISA). And LTC4 content, p62 mRNA and protein expressions in lung airway epithelial cells were detected by quantitative real-time fluorescence polymerase chain reaction (Real-time PCR) and Western blot. Result:Compared with the normal group, ELISA results showed that IL-1β, TNF-α, LTB4, and LTC4 in the model group were significantly increased (P<0.01). Compared with the model group, IL-1β, TNF-α, LTB4, LTC4 in cell supernatants in each administration group were significantly reduced (P<0.01), mRNA and protein expressions in p62 showed that compared with the normal group, mRNA and protein expressions in p62 of model group significantly decreased (P<0.01). Compared with the model group, the mRNA and protein expressions of p62 in each administration group significantly increased to different degrees (P<0.01). The expression of autophagy in Qingjin Huatantang high-dose group and western medicine group was comparable. Conclusion:Qingjin Huatantang can reduce the inflammatory response in airway epithelial cells, which may be related to the regulation of autophagy protein p62.

Epigallocatechin-3-gallate (EGCG) as a pro-osteogenic agent to enhance osteogenic differentiation of mesenchymal stem cells from human bone marrow: an in vitro study.

The proliferation and osteogenic capacity of mesenchymal stem cells (MSCs) needs to be improved for their use in cell-based therapy for osteoporosis. (-)-Epigallocatechin-3-gallate (EGCG), one of the green tea catechins, has been widely investigated in studies of osteoblasts and osteoclasts. However, no consensus on its role as an osteogenic inducer has been reached, possibly because of the various types of cell lines examined and the range of concentrations of EGCG used. In this study, the osteogenic effects of EGCG are studied in primary human bone-marrow-derived MSCs (hBMSCs) by detecting cell proliferation, alkaline phosphatase (ALP) activity and the expression of relevant osteogenic markers. Our results show that EGCG has a strong stimulatory effect on hBMSCs developing towards the osteogenic lineage, especially at a concentration of 5 µM, as evidenced by an increased ALP activity, the up-regulated expression of osteogenic genes and the formation of bone-like nodules. Further exploration has indicated that EGCG directes osteogenic differentiation via the continuous up-regulation of Runx2. The underlying mechanism might involve EGCG affects on osteogenic differentiation through the modulation of bone morphogenetic protein-2 expression. EGCG has also been found to promote the proliferation of hBMSCs in a dose-dependent manner. This might be associated with its antioxidative effect leading to favorable amounts of reactive oxygen species in the cellular environment. Our study thus indicates that EGCG can be used as a pro-osteogenic agent for the stem-cell-based therapy of osteoporosis.

[Study on relationship between quantitative data of tongue picture and state of illness in 224 patients with severe acute respiratory syndrome].

OBJECTIVE: To observe the characteristics of tongue proper and tongue coating in patients with severe acute respiratory syndrome (SARS) and to explore the relationship between tongue picture and state of illness. METHODS: Tongue picture was taken by digital camera and colors (red, green and blue) of tongue proper and coating were analyzed quantitatively with image processing software. RESULTS: In the 69 patients of acute stage, the color of tongue proper was mostly light red (51 patients, 73.9%), with significant difference in comparing with other colors (P < 0.01). The color of tongue coating was mostly thin yellow (32 patients, 46.4%), and thin white was the second (29 patients, 42.0%). There was swollen tongue body in 5 patients (7.2%), teeth print on tongue margin in 12 cases (17.4%). In the 155 patients of recovery stage, the color of tongue proper was mostly dark pale (72 patients, 46.5%), the second light red (68 patients, 43.9%), color of tongue coating was mostly thin white (80 patients, 51.6%), which was significantly higher than other colors (P < 0.01), the second was yellow in tongue root region (31 patients, 20.0%). Swollen tongue body was found in 23 patients (14.8%) and teeth print on margin was found in 19 patients (12.3%). Most patients of ordinary state had light red tongue proper and thin white coating, patients of severe state mostly had dark pale tongue proper and yellow coating in root region, and the critical patients were mostly with dark pale proper and thick yellow coating. Patients with affected lung > or = 3 lobules mostly had pale dark proper and yellow coating on root, but those with involved lung < 3 lobules mostly had light red proper and thin white coating. CONCLUSION: The colors detected quantitatively by the method described above could comparatively reflect the difference of tongue proper and coating sensitively. Tongue picture is one of the objective evidence for judging state of illness and Syndrome Differentiation based on treatment in SARS patients.

Study on relationship between quantitative data of tongue picture and state of illness in 224 patients with severe acute respiratory syndrome / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To observe the characteristics of tongue proper and tongue coating in patients with severe acute respiratory syndrome (SARS) and to explore the relationship between tongue picture and state of illness.</p><p><b>METHODS</b>Tongue picture was taken by digital camera and colors (red, green and blue) of tongue proper and coating were analyzed quantitatively with image processing software.</p><p><b>RESULTS</b>In the 69 patients of acute stage, the color of tongue proper was mostly light red (51 patients, 73.9%), with significant difference in comparing with other colors (P < 0.01). The color of tongue coating was mostly thin yellow (32 patients, 46.4%), and thin white was the second (29 patients, 42.0%). There was swollen tongue body in 5 patients (7.2%), teeth print on tongue margin in 12 cases (17.4%). In the 155 patients of recovery stage, the color of tongue proper was mostly dark pale (72 patients, 46.5%), the second light red (68 patients, 43.9%), color of tongue coating was mostly thin white (80 patients, 51.6%), which was significantly higher than other colors (P < 0.01), the second was yellow in tongue root region (31 patients, 20.0%). Swollen tongue body was found in 23 patients (14.8%) and teeth print on margin was found in 19 patients (12.3%). Most patients of ordinary state had light red tongue proper and thin white coating, patients of severe state mostly had dark pale tongue proper and yellow coating in root region, and the critical patients were mostly with dark pale proper and thick yellow coating. Patients with affected lung > or = 3 lobules mostly had pale dark proper and yellow coating on root, but those with involved lung < 3 lobules mostly had light red proper and thin white coating.</p><p><b>CONCLUSION</b>The colors detected quantitatively by the method described above could comparatively reflect the difference of tongue proper and coating sensitively. Tongue picture is one of the objective evidence for judging state of illness and Syndrome Differentiation based on treatment in SARS patients.</p>