The multifaceted mechanisms of Dihydrotanshinone I in the treatment of tumors.

The morbidity and mortality of malignant tumors are progressively rising on an annual basis. Traditional Chinese Medicine (TCM) holds promise as a possible therapeutic agent for the avoidance or therapy of malignant tumors. Salvia miltiorrhiza Bunge (Danshen), a traditional Asian functional food, has therapeutic characteristics in application for the treatment of malignant tumors. Dihydrotanshinone I (DHTS) is the principal lipophilic phenanthraquinone compound found in Salvia miltiorrhiza Bunge, whose anti-tumor effect has attracted widespread attention. The anti-tumor effects include inhibiting cancer cell proliferation, triggering apoptosis of tumor cells, inducing ferroptosis in tumor cells, inhibiting tumor cell invasion and metastasis, and improving drug resistance of tumor cells. In this paper, we summarized and analyzed the mechanisms and targets of anti-tumor effect of DHTS, providing new ideas and establishing a solid theoretical basis for the future advancement and clinical treatment of DHTS.

Research progress of traditional Chinese medicine in the treatment of allergic rhinitis.

Allergic rhinitis, one of the common diseases in otolaryngology, has shown an increasing incidence under the influence of various geographical, cultural and economic factors, making it a common and serious global public health problem. Modern medicine uses medication as the primary therapy for allergic rhinitis, but poor symptom control and easy relapse are the disadvantages of this treatment. However, Traditional Chinese medicine, with its long history, has treated allergic rhinitis by symptomatic treatment according to pattern differentiation with its unique insights and methods, which are effective and safe in numerous clinical studies. Therefore, this paper describes TCM decoction, acupuncture, moxibustion, acupoint application, catgut-embedding therapy and ear acupuncture in the treatment of AR. This study aims to provide more personalized and precise treatment for allergic rhinitis patients by investigating the mechanism of action, clinical research and development of traditional Chinese medicine treatments.

Dihydrotanshinone Attenuates LPS-Induced Acute Lung Injury in Mice by Upregulating LXRα.

Dihydrotanshinone (DIH) is an extract of Salvia miltiorrhiza Bunge. It has been reported that DIH could regulate NF-κB signaling pathway. The aim of this study was to investigate whether DIH could protect mice from lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice. In this study, sixty mice were randomly divided into five groups, one group as blank control group, the second group as LPS control group, and the last three groups were pre-injected with different doses of DIH and then inhaled LPS for experimental comparison. After 12 h of LPS treatment, the wet-dry ratio, histopathlogical changes, and myeloperoxidase (MPO) activity of lungs were measured. In addition, ELISA kits were used to measure the levels of TNF-α and IL-1ß inflammatory cytokines in bronchoalveolar lavage fluids (BALF), and western blot analysis was used to measure the activity of NF-κB signaling pathway. The results demonstrated that DIH could effectively reduce pulmonary edema, MPO activity, and improve the lung histopathlogical changes. Furthermore, DIH suppressed the levels of inflammatory cytokines in BALF, such as TNF-α and IL-1ß. In addition, DIH could also downregulate the activity of NF-κB signaling pathway. We also found that DIH dose-dependently increased the expression of LXRα. In addition, DIH could inhibit LPS-induced IL-8 production and NF-κB activation in A549 cells. And the inhibitory effects were reversed by LXRα inhibitor geranylgeranyl pyrophosphate (GGPP). Therefore, we speculate that DIH regulates LPS-induced ALI in mice by increasing LXRα expression, which subsequently inhibiting NF-κB signaling pathway.

Ultrasensitive detection of trypsin in serum via nanochannel device.

A highly sensitive trypsin sensing system in serum was developed by using an anodic alumina oxide (AAO)-based, trypsin substrate-decorated hybrid ion permeation membrane. Owing to the trypsin-triggered peptide hydrolyzation reaction, the surface electrical feature of the peptide-decorated hybrid ion membrane changed. The electric double layer effect reduces the effective ion current diameter in the AAO nano unit, so that the ion current rectification ratio will be enhanced, realizing the quantitative detection of trypsin. The lowest detection concentration can be achieved as low as 0.1 pM. This method is no need for sample pre-preparation, easy to operate, highly sensitive, and also applicable to other enzyme evaluation systems by changing corresponding substrates. This study provides a new idea for selective measurements of proteases in complex biological samples.

Utilization and associated factors of reproductive health services among 20-39-year-old women in rural China: a cross-sectional study.

BACKGROUND: The use of reproductive health (RH) services is important to promote RH. However, little is known about RH services in rural areas, especially in low- and middle-income countries. China is the most populous country in the world, and 40.4% of its population is rural. Our study determined the utilization of and factors associated with RH services in rural China. METHODS: A cross-sectional study of 978 20- to 39-year-old women was performed in four villages of four cities in Hunan Province. A researcher-created structured questionnaire was used to collect the data. The data were entered into EpiData v3.0 and analysed using SPSS v18.0. Statistical significance was defined as a two-sided P-value of less than 0.05. Descriptive statistics were used to examine the socio-demographic factors and the use of RH services by the sample population. Chi-square tests were used to assess associations between categorical variables. Logistic regression analyses were performed to examine factors that correlated with the use of RH services. RESULTS: The top three services used were antenatal examinations (90.2%), postpartum visits (73.0%) and free folic acid supplements (71.6%). Age, monthly household income, employment, spousal education level, and artificial abortion history were associated with RH service utilization (P < 0.05). The most desired RH service was cervical/breast cancer prevention services (58.9%). The most preferred method participants used to obtain information on RH services was the internet. CONCLUSIONS: The utilization rate for RH services in rural China needs improvement. Future efforts should target high-risk populations of women by providing them with RH-related information and cultivating positive attitudes towards RH services.

Reproductive health (RH) services are recognized worldwide as a cost-effective strategy to promote RH. However, little is known about RH services in rural areas, especially in low- and middle-income countries. China is the most populous country in the world, and 40.4% of its population is rural. Due to the implementation of China's universal two-child policy, women between 20 and 39 years old are likely to experience more RH problems related to childbirth. Our study investigated the utilization of and factors associated with RH services in rural China. The top three services used among the 978 participants were antenatal examinations (90.2%), postpartum visits (73.0%) and free folic acid supplements (71.6%). Age, monthly household income, employment, spousal education level, and artificial abortion history were associated with RH service utilization. The participants most desired services pertained to the prevention of cervical/breast cancer, and the most preferred methods used to obtain information related to RH services was the internet.In conclusion, the utilization of RH services requires improvement, and future efforts should target high-risk populations of women by providing them with RH-related information and cultivating positive attitudes towards RH services.

[Effect of electroacupuncture on angiopoietin-1 in spinal cord of rats with neuropathic pain].

OBJECTIVE: To observe the effect of electroacupuncture (EA) on the behavior, histomorphology and the expression of angiopoietin-1 (Angpt-1) in rats with spinal nerve injury, so as to explore its mechanism on neuropathic pain. METHODS: Forty-five male SD rats were randomly divided into sham, model and EA groups (n=15 rats in each group). Spinal nerve ligation (SNL) of the L5 lumbar vertebra was performed to establish a rat model of neuropathic pain. The rats in the EA group were given EA at "Zusanli" (ST36) and "Kunlun" (BL60) of the operation side with continuous wave at a frequency of 2 Hz and an intensity of 1.5 mA once a day, 30 minutes each time for 7 days. The sham group only exposed L5 spinal nerves without ligation. Mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) were observed and recorded before modeling and on days 3,5,7,10,12 and 14 after modeling. L4-L6 segments of spinal cord were taken and the morphological changes of spinal dorsal horn were observed by HE staining. The changes of spinal dorsal horn nerve fiber structure were observed by silver plating staining. Angpt-1 expression was detected by Western blot and immunohistochemistry. RESULTS: Compared with the sham group, the model group had significant reductions in MWT and TWL at each time point (P<0.01); compared with the model group, the EA group had significant increases in MWT and TWL on days 10,12 and 14 after intervention (P<0.05, P<0.01). HE staining showed that in the model group, the spinal dorsal horn showed degeneration and necrosis of neurons, nuclear fixation and shrinkage, and loose surrounding tissues. The degree of tissue damage of the EA group was milder than that of the model group. The silver staining results showed the model group had obvious neuronal fibrillary tangles, while there were fewer neuronal fibrillary tangles in the EA group. Compared with the sham group, the Angpt-1 expression in the model group was significantly decreased (P<0.01), and compared with the model group, the EA group had a significant increase in the expression of Angpt-1 (P<0.01). CONCLUSION: EA can promote the recovery of nerve function in SNL rats by up-regulating Angpt-1 expression.

Ouabain regulates kidney metabolic profiling in rat offspring of intrauterine growth restriction induced by low-protein diet.

AIMS: Intrauterine growth restriction (IUGR) can increase the risk of hypertension and kidney disease at adulthood due to fetal programming. In our previous study, we found that supplementation with low concentration of ouabain during pregnancy could restore glomerulus numbers at birth, rescuing kidney development. However, the metabolic pattern of kidney in IUGR offspring and the effect of ouabain have not been evaluated. MAIN METHODS: In this study, based on GC-MS and LC-MS platforms, we used the protein restriction rat model to explore the molecular mechanisms of kidney damage induced by IUGR and the protective effect of ouabain. KEY FINDINGS: The results showed that malnutrition could induce IUGR in rat offspring at the 20th gestational day but ouabain treatment could partially reverse the body and kidney weight loss. Ouabain treatment could upregulate arginine, N-acetylornithine and carbamoyl phosphate as well as adenine nucleotide and guanine nucleotide downregulated by low-protein diet. Moreover, six metabolites were identified to be significantly correlated with fetal kidney weight, with 3 metabolites involved in arginine metabolism (arginine, N-acetylornithine, urea) and UDP-glucuronate correlated positively, while lysine and anthranilate correlated negatively. SIGNIFICANCE: The results suggested that the underlying mechanism of ouabain against renal maldevelopment involved the metabolic regulation, particularly the arginine metabolism, which played an important role in the development of fetal kidney.

Intracellular pH-propelled assembly of smart carbon nanodots and selective photothermal therapy for cancer cells.

A kind of smart carbon nanodots (CNDs) with the pH response feature was prepared by the one-pot hydrothermal treatment of citric acid and dicyandiamide, which was used for the differentiation of cancer/normal cells and the selective photothermal therapy (PTT) of cancer cells. When the smart CNDs were cultured with cells, they were highly internalized in the lysosomes of cells. Since the small-sized CNDs (about 5 nm) tends to form aggregation (as large as about 20 nm or even larger) under an acid condition (pH = 4.7) due to the electrostatic attraction produced by the surface protonation, relatively severer aggregation of the CNDs were observed in liver cancer cells (HepG2 cells) relative to normal ones (LO2 cells) due to a relative lower pH in the lysosomes of HepG2 cells, which endows them a new strong absorption band at longer wavelengths (450-900 nm) and a higher photothermal conversion efficiency (42.13 %), benefiting to differentiated PTT. The flow cytometric data indicates strong photothermal ablation (8 min, 509.6 mW/cm2) for cancer cells with the assistance of these smart CNDs achieves 82 % death rate of cancer cells, while much less damage is observed on the normal cells (6.35 %). To the best of our knowledge, this is the first report about CNDs for selective PTT owing to their intrinsic property without the aid of any other targeting ligands. These smart CNDs are also available for other acid-responsive sensing systems, and this study inspires us in the synthesis of near-infrared featured carbon materials.

Epigenetic Landscape Changes Due to Acupuncture Treatment: From Clinical to Basic Research / 中国结合医学杂志

Acupuncture has been widely used for treating diseases since the ancient days in China, but the mechanism by which acupuncture exerts such powerful roles is unclear. Epigenetics, including DNA methylation, histone modification, and post-transcriptional regulation of miRNAs, is the study of heritable changes in gene expression that do not include DNA sequence alterations. Epigenetics has become a new strategy for the basic and clinical research of acupuncture in the last decade. Some investigators have been trying to illustrate the mechanism of acupuncture from an epigenetics perspective, which has shed new lights on the mechanisms and applications of acupuncture. Moreover, the introduction of epigenetics into the regulatory mechanism in acupuncture treatment has provided more objective and scientific support for acupuncture theories and brought new opportunities for the improvement of acupuncture studies. In this paper, we reviewed the literatures that has demonstrated that acupuncture could directly or indirectly affect epigenetics, in order to highlight the progress of acupuncture studies correlated to epigenetic regulations. We do have to disclose that the current evidence in this review is not enough to cover all the complex interactions between multiple epigenetic modifications and their regulations. However, the up-to-date results can help us to better understand acupuncture's clinical applications and laboratory research.

Research and thinking of acupuncture on promoting white adipose tissue browning / 针刺研究

Acupuncture has become an effective approach in clinic for treating obesity, but its mechanism has not been clarified yet. A large number of researches have been conducted on the obesity mechanism in the aspects of neurophysiological regulation, feeding center regulation and peripheral digestion and absorption regulation at home and abroad. But, regarding the main storage site of excess energy, i．e. the remodeling and functional regulation of white adipose tissue (WAT), is still a new field in research. In the paper, focusing on the new filed of weight loss, in view of the promotion of WAT browning through the re-gulation of UCP1 and PPARγ signal pathway with acupuncture, the potential peripheral mechanism of acupuncture was explored on weight loss.

Tracing the molecular dynamics of living mitochondria under phototherapy via surface-enhanced Raman scattering spectroscopy.

Subcellular mitochondrion has become a target for improving the therapeutic efficiency and reducing side damage to normal cells via a combination of many therapeutic strategies. However, the underlying molecular mechanisms associated with cell death induced by subcellular dysfunction remain unknown or disputed. In this study, we investigated the dynamic molecular changes of living mitochondria upon phototherapy (photothermal therapy plus photodynamic therapy, PTT & PDT) by surface-enhanced Raman scattering spectroscopy (SERS) and intended to disclose the photo-induced cell death route in breast cancer cells (MCF-7) taking into account the mitochondrion. Indocyanine green (ICG), a Food and Drug Administration (FDA)-approved clinic blood-injection near-infrared angiographic contrast agent and a PTT & PDT drug, was used for the evaluation of the phototherapy effect. The results revealed that the content of phenylalanine (Phe) in mitochondria evidently increased during the phototherapy-induced cell death process. Moreover, the phototherapy-induced cell apoptosis was mainly regulated through the DNA structures. We expect that the understanding of mitochondrial molecular stress responses will be helpful for the diagnosis and therapy of cellular processes associated with mitochondria and provide valuable guidance for the further design and development of more effective therapeutic platforms and methods at the sub-cellular level.

Efficacy and Safety of Vitamin D Supplementation in Patients With Systemic Lupus Erythematosus: A Meta-analysis of Randomized Controlled Trials.

BACKGROUND: The efficacy of vitamin D supplementation in patients with systemic lupus erythematosus (SLE) remains uncertain. This meta-analysis aimed to systematically evaluate the efficacy and safety of vitamin D supplementation in patients with SLE. MATERIALS AND METHODS: Randomized controlled trials (RCTs) were searched in PubMed, Embase, Cochrane CENTRAL and Web of Science databases. The retrieved studies were subjected to meta-analysis using the fixed-effect or random-effect model. RESULTS: Five eligible RCTs enrolling 490 participants were included. Compared to the placebo treatment, vitamin D supplementation significantly increased the level of serum 25-hydroxyvitamin D (25(OH)D) (5 trials, 490 participants: standard mean difference (SMD) = 2.072, 95% CI: 1.078-3.066, P < 0.001). The pooled result from 2 RCTs showed that vitamin D supplementation decreased the fatigue severity scale scores in patients with SLE (2 trials, 79 participants: SMD = -1.179, 95% CI: -1.897 to -0.460, P = 0.001). The SLE disease activity index scores and positivity of anti-double-stranded DNA antibodies (anti-dsDNA) did not differ significantly (4 trials, 223 participants: SMD = -0.507, 95% CI: -1.055-0.041, P = 0.070; 3 trials, 361 participants: Risk ratio = 0.880, 95% CI: 0.734-1.054, P = 0.165) between the vitamin D supplementation group and the placebo treatment group. None of the included studies reported severe adverse events associated with vitamin D supplementation. CONCLUSIONS: This meta-analysis suggested that vitamin D supplementation is effective in increasing the serum 25(OH)D levels, may improve fatigue, and is well-tolerated in patients with SLE, however, it does not seem to have significant effects in decreasing the positivity of anti-dsDNA and disease activity.

Suppression of GHS-R in AgRP Neurons Mitigates Diet-Induced Obesity by Activating Thermogenesis.

Ghrelin, an orexigenic hormone released primarily from the gut, signals the hypothalamus to stimulate growth hormone release, enhance appetite and promote weight gain. The ghrelin receptor, aka Growth Hormone Secretagogue Receptor (GHS-R), is highly expressed in the brain, with highest expression in Agouti-Related Peptide (AgRP) neurons of the hypothalamus. We recently reported that neuron-specific deletion of GHS-R completely prevents diet-induced obesity (DIO) in mice by activating non-shivering thermogenesis. To further decipher the specific neuronal circuits mediating the metabolic effects of GHS-R, we generated AgRP neuron-specific GHS-R knockout mice (AgRP-Cre;Ghsrf/f). Our data showed that GHS-R in AgRP neurons is required for ghrelin's stimulatory effects on growth hormone secretion, acute food intake and adiposity, but not for long-term total food intake. Importantly, deletion of GHS-R in AgRP neurons attenuated diet-induced obesity (DIO) and enhanced cold-resistance in mice fed high fat diet (HFD). The HFD-fed knockout mice showed increased energy expenditure, and exhibited enhanced thermogenic activation in both brown and subcutaneous fat; this implies that GHS-R suppression in AgRP neurons enhances sympathetic outflow. In summary, our results suggest that AgRP neurons are key site for GHS-R mediated thermogenesis, and demonstrate that GHS-R in AgRP neurons plays crucial roles in governing energy utilization and pathogenesis of DIO.

Effects of Ziziphus jujuba fruit extracts on cytochrome P450 (CYP1A2) activity in rats / 中国天然药物

Drug-drug interactions have become a serious problem in the clinic, since plant-based medicines are extensively used. The present study investigated the effects of Ziziphus jujuba fruit (ZJ) extract on the pharmacokinetics of phenacetin, a typical substrate of a cytochrome P450 enzyme CYP 1A2, in rats. The rats were pretreated with the water extract (1.0 g · kg(-1)) or the ethanolic extract (3.6 g · kg(-1)) of ZJ for 10 days, and the pharmacokinetics of phenacetin was investigated after intravenous administration. In an in vitro assay, acetaminophen formation in the hepatic microsomes of ZJ-treated rats was investigated to assess CYP1A2 activity. Our results demonstrated that the treatment with the water and ethanolic extracts of ZJ decreased the plasma concentration of phenacetin and increased the plasma concentration of acetaminophen, resulting in a 43.2% and 15.5% reduction in the AUC0-120 of phenacetin, respectively, and a 53.2% and 64.9% increase in the AUC0-120 of acetaminophen, respectively after intravenous administration. The water or ethanolic extract of ZJ significantly increased the clearance of phenacetin and acetaminophen formation in hepatic microsomes. In conclusion, ZJ extracts displayed effects on the pharmacokinetics of phenacetin and increased the CYP1A2 activity in rats. Therefore, precaution on drug-drug interactions should be taken when ZJ is co-administered with drugs metabolized by CYP1A2, which may result in decreased concentrations of these drugs.

Effect of dehydroepiandrosterone administration in patients with poor ovarian response according to the Bologna criteria.

BACKGROUND: Dehydroepiandrosterone (DHEA) is now widely used as an adjuvant to IVF treatment protocols in poor responders. However, clinical evidence for DHEA on improvement of ovarian response and IVF outcome is still limited, the validity of the results of the earlier studies, especially the varied inclusion criteria, is a subject of debate. Recently, the ESHRE Working Group developed a new definition, the Bologna criteria. The aim of the current study was to investigate the potential effect of DHEA treatment on in vitro fertilization (IVF) outcome of poor ovarian responders that fulfill the Bologna criteria. METHODS: This study investigated 386 poor ovarian responders that fulfill the Bologna criteria. Patients underwent IVF-ET treatment with the GnRH antagonist protocol. The study group contained 189 patients, who received 75 mg of DHEA daily (25 mg three times daily) before the IVF cycle. The control group was composed of 197 patients who received infertility treatment, but did not receive DHEA. The IVF outcome parameters in each group were compared. RESULTS: The study and control groups did not show statistically significant differences in terms of patient demographics characteristics, mean numbers of oocytes retrieved, mature oocytes, fertilization rate, cleavage rate, or embryo availability. While the DHEA group demonstrated significantly higher implantation rates (18.7% vs. 10.1%; P<0.01) and ongoing PRs (26.7% vs. 15.8%; P<0.05) as compared with the control. CONCLUSIONS: DHEA pre-treatment does not significantly increase oocyte yield. However, the ongoing PRs in this subgroup of women are significantly higher after DHEA administration, suggesting that DHEA may increase IVF results by improving oocyte and embryo quality.

Preliminary study on the mechanism of oridonin-induced apoptosis in human squamous cell oesophageal carcinoma cell line EC9706.

OBJECTIVE: To study the apoptosis-inducing effect of the Chinese medicine oridonin in the human oesophageal squamous cell carcinoma cell line EC9706, in vitro. METHODS: The effect of oridonin on cell proliferation was studied using the colorimetric 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Effects on the cell cycle and apoptosis were studied by flow cytometry; effects on intracellular Ca(2+) concentration were studied by measuring the fluorescence intensity of a fluorescent Ca(2+) probe by laser scanning confocal microscopy. RESULTS: The EC9706 cell-proliferation rate decreased with time and oridonin concentration (10-40 µmol/l). The number of cells in G0 and G1 phases increased significantly following exposure to oridonin for 48 and 72 h respectively, and oridonin was shown to be most effective at inducing apoptosis in EC9706 cells at 40 µmol/l. Compared with the control group, all concentrations of oridonin tested (10-40 µmol/l) significantly increased the Ca(2+) fluorescence intensity of EC9706 cells. CONCLUSIONS: Oridonin was shown to inhibit proliferation and induce apoptosis in the human oesophageal squamous cell carcinoma cell line EC9706, in vitro. These data provide preliminary experimental evidence for the anticancer effects of oridonin, which is as a traditional Chinese medicine used to treat various cancers, including oesophageal squamous cell carcinoma. Further studies are required to elucidate the mode of action.

[Effects of acupuncture on default mode network images of chronic sciatica patients in the resting network state].

OBJECTIVE: To observe the functional magnetic resonance imaging (fMRI) data changes of default mode network (DMN) in chronic sciatica patients in the resting network state treated by acupuncture, and to study the correlation between DMN and the consisting effects after acupuncture analgesia. METHODS: Weizhong (BL40) and Huantiao (GB30) of the patients' lower limbs were selected as the main points to acupuncture for ten times. The whole brain was scanned using fMRI. The independent component analysis (ICA) was adopted to get DMN information. The brain DMN function link was analyzed in the two groups of subjects. RESULTS: The DMN images were obtained in all subjects after DMN fMRI data processing. The main DMN differences between the sciatica patients group and the healthy control group were demonstrated as decreased activities of DLPFC and anterior cingulate cortex (ACC). After acupuncture, activities of these regions basically recovered to normal. The DMN of healthy volunteers shown by fMRI data in the RNS mainly existed in the precuneus, BA7, BA10, and ACC. CONCLUSION: MRI images of DMN in the RNS could reflect chronic pain, which was suitable for studies on the effects after acupuncture analgesia.