Ginger inhibits the invasion of ovarian cancer cells SKOV3 through CLDN7, CLDN11 and CD274 m6A methylation modifications.

BACKGROUND: Ginger is a common aromatic vegetable with a wide range of functional ingredients and considerable medicinal and nutritional properties. Numerous studies have shown that ginger and its active ingredients have suppressive effects on manifold tumours, including ovarian cancer (OC). However, the molecular mechanism by which ginger inhibits OC is not clear. The aim of this study was to investigate the function and mechanism of ginger in OC. METHODS: The estimation of n6-methyladenosine (m6A) levels was performed using the m6A RNA Methylation Quantification Kit, and RT-qPCR was used to determine the expression of m6A-related genes and proteins. The m6A methylationome was detected by MeRIP-seq, following analysis of the data. Differential methylation of genes was assessed utilizing RT-qPCR and Western Blotting. The effect of ginger on SKOV3 invasion in ovarian cancer cells was investigated using the wound healing assay and transwell assays. RESULTS: Ginger significantly reduced the m6A level of OC cells SKOV3. The 3'UTR region is the major site of modification for m6A methylation, and its key molecular activities include Cell Adhesion Molecules, according to meRIP-seq results. Moreover, it was observed that Ginger aids significantly in downregulating the CLDN7, CLDN11 mRNA, and protein expression. The results of wound healing assay and transwell assay showed that ginger significantly inhibited the invasion of OC cells SKOV3. CONCLUSIONS: Ginger inhibits ovarian cancer cells' SKOV3 invasion by regulating m6A methylation through CLDN7, CLDN11, and CD274.

Icariin inhibits hypertrophy by regulation of GPER1 and CaMKII/HDAC4/MEF2C signaling crosstalk in ovariectomized mice.

Icariin (ICA), a flavonoid phytoestrogen, was isolated from traditional Chinese medicine Yin Yang Huo (Epimedium brevicornu Maxim.). Previous studies reporting the cardioprotective effects of ICA are available; however, little is known about the impact of ICA on cardioprotection under conditions of reduced estrogen levels. This study aimed to provide detailed information regarding the antihypertrophic effects of ICA in ovariectomized female mice. Female mice were subjected to ovariectomy (OVX) and transverse aortic constriction and then orally treated with ICA at doses of 30, 60 or 120 mg/kg/day for 4 weeks. Morphological assessments, echocardiographic parameters, histological analyses, and immunofluorescence were performed to evaluate cardiac hypertrophy. Cardiomyocytes from mice or rats were stimulated using phenylephrine, and cell surface and hypertrophy markers were tested using immunofluorescence and qPCR. Western blotting, qPCR, and luciferase reporter gene assays were used to assess the expression of proteins and mRNA and further investigate the proteins related to the G-protein coupled estrogen receptor (GPER1) and CaMKII/HDAC4/MEF2C signaling pathways in vivo and in vitro. ICA blocks cardiac hypertrophy induced by pressure overload in OVX mice. Additionally, we demonstrated that ICA activated GPER1 and inhibited the nuclear export or promoted the nuclear import of histone deacetylase 4 (HDAC4) through regulation of phosphorylation of calmodulin-dependent protein kinase II (CaMKII) and further improved the repression of myocyte enhancer factor-2C (MEF2C). ICA ameliorated cardiac hypertrophy in OVX mice by activating GPER1 and inhibiting the CaMKII/HDAC4/MEF2 signaling pathway.

Efficacy and Safety of Panax notoginseng Saponins in the Treatment of Adults With Ischemic Stroke in China: A Randomized Clinical Trial.

Importance: Preclinical and clinical studies have suggested the neuroprotective effect of Panax notoginseng saponins (Xuesaitong soft capsules). However, robust evidence in patients with ischemic stroke is lacking. Objective: To assess the efficacy and safety of Xuesaitong soft capsules in patients with ischemic stroke. Design, Setting, and Participants: This multicenter, double-blind, placebo-controlled randomized clinical trial was conducted at 67 tertiary health centers in China from July 1, 2018, to June 30, 2020. Included patients were aged 18 to 75 years with a diagnosis of ischemic stroke and a National Institutes of Health Stroke Scale score between 4 and 15. Interventions: Eligible patients were randomly assigned within 14 days after symptom onset to receive either treatment with Xuesaitong soft capsules (120 mg orally twice daily) or placebo (120 mg orally twice daily) for 3 months. Main Outcomes and Measures: The primary outcome was functional independence at 3 months, defined as a modified Rankin Scale score of 0 to 2. Results: Among 3072 eligible patients with ischemic stroke who were randomized, 2966 (96.5%) were included in the modified intention-to-treat cohort (median [IQR] age, 62 [55-68] years; 1982 male [66.8%]). The number of patients who achieved functional independence at 3 months was 1328 (89.3%) in the Xuesaitong group and 1218 (82.4%) in the control group (odds ratio, 1.95; 95% CI, 1.56-2.44; P < .001). In the safety cohort, serious adverse events occurred in 15 of 1488 patients (1.0%) in the Xuesaitong group and 16 of 1482 (1.1%) in the control group (P = .85). Conclusions and Relevance: In this randomized clinical trial, Xuesaitong soft capsules significantly increased the likelihood of functional independence at 3 months in patients with ischemic stroke, indicating that this may be a safe and effective alternative therapy to improve prognosis in this population. Trial Registration: Chinese Clinical Trial Registry Identifier: ChiCTR1800016363.

Molecular mechanism of ferulic acid and its derivatives in tumor progression.

Cancer is a significant disease that poses a major threat to human health. The main therapeutic methods for cancer include traditional surgery, radiotherapy, chemotherapy, and new therapeutic methods such as targeted therapy and immunotherapy, which have been developed rapidly in recent years. Recently, the tumor antitumor effects of the active ingredients of natural plants have attracted extensive attention. Ferulic acid (FA), (3-methoxy-4-hydroxyl cinnamic), with the molecular formula is C10H10O4, is a phenolic organic compound found in ferulic, angelica, jujube kernel, and other Chinese medicinal plants but is also, abundant in rice bran, wheat bran, and other food raw materials. FA has anti-inflammatory, analgesic, anti-radiation, and immune-enhancing effects and also shows anticancer activity, as it can inhibit the occurrence and development of various malignant tumors, such as liver cancer, lung cancer, colon cancer, and breast cancer. FA can cause mitochondrial apoptosis by inducing the generation of intracellular reactive oxygen species (ROS). FA can also interfere with the cell cycle of cancer cells, arrest most cancer cells in G0/G1 phase, and exert an antitumor effect by inducing autophagy; inhibiting cell migration, invasion, and angiogenesis; and synergistically improving the efficacy of chemotherapy drugs and reducing adverse reactions. FA acts on a series of intracellular and extracellular targets and is involved in the regulation of tumor cell signaling pathways, including the phosphatidylinositol 3 kinase (PI3K)/protein kinase B (AKT), B-cell lymphoma-2 (Bcl-2), and tumor protein 53 (P53) pathways and other signaling pathways. In addition, FA derivatives and nanoliposomes, as platforms for drug delivery, have an important regulatory effect on tumor resistance. This paper reviews the effects and mechanisms of antitumor therapies to provide new theoretical support and insight for clinical antitumor therapy.

Screening redox stability of iron rich by-products for effective phosphate immobilisation in freshwater sediments.

Iron (Fe) rich by-products can be added to lake or river sediments to immobilise phosphate (PO4) and lower eutrophication risks. These Fe materials differ in mineralogy and specific surface area, hence differing in PO4 sorption capacity and stability under reducing conditions. This study was set up to identify key properties of these amendments in their capacity to immobilise PO4 in sediments. Eleven Fe rich by-products, collected from drinking water treatment plants and acid mine drainage, were characterised. The PO4 adsorption to these by-products was first determined under aerobic conditions and the solid-liquid distribution coefficient KD for PO4 correlated strongly to oxalate extractable Fe content. A static sediment-water incubation test was subsequently used to evaluate the redox stability of these by-products. The reductive processes gradually released Fe to solution and more Fe was release from the amended than from the control sediments. The total Fe release to solution was positively related to ascorbate reducible Fe fractions in the by-products, suggesting that such fractions indicate potential loss of P retention capacity on the long term. The final PO4 concentration in the overlying water was 5.6 mg P L-1 in the control and was successfully lowered by factor 30-420 depending on the by-product. The factor by which solution PO4 was reduced in Fe treatments increased with increasing KD determined under aerobic conditions. This study suggests that efficient by-products to trap P in sediments are characterised by a high oxalate Fe content and a low reducible Fe fraction.

Effect of external and internal loading on source-sink phosphorus dynamics of river sediment amended with iron-rich glauconite sand.

Glauconite sands (GS) are abundantly available iron (Fe)-rich minerals that are efficient in lowering the release of phosphorus (P) from sediments to the overlying water. Many river sediments are, however, net sinks for P rather than sources and it is unclear if these GS minerals also enhance the P uptake from water. This is because the concentration of Fe(III) minerals at the sediment-water interface (SWI) depends on the redox potential that is affected by physicochemical processes. This study was set-up to investigate if a sediment amendment with GS can both lower P release from the sediment and enhance P uptake from the overlying water. The P fluxes across the SWI were compared between GS-amended (added at 10% weight fraction) and non-amended river sediment in static (incubation) and dynamic (flume) systems. The net P uptake was measured in response to a pulse external P loading (0.5-5 mg P L-1). Sodium glutamate was added to all treatments to simulate water with a high oxygen demand. Before the P pulse, the GS-amended sediments released significantly less P to the overlying water than the non-amended sediments in both static as dynamic systems. Spiking the water reverted the net P flux over the SWI only in the dynamic system, and the net P uptake in the sediment was factor two larger in GS-amended sediment compared to the non-amended sediment. This study showed that GS addition not only reduced internal P release, but also enhanced P uptake from the overlying water. However, the long-term efficiency in streams likely decreases over time due to saturation processes.

Aquaporins: A new target for traditional Chinese medicine in the treatment of digestive system diseases.

Aquaporins (AQPs) are a family of transmembrane proteins expressed in various organ systems. Many studies have shown that the abnormal expression of AQPs is associated with gastrointestinal, skin, liver, kidneys, edema, cancer, and other diseases. The majority of AQPs are expressed in the digestive system and have important implications for the physiopathology of the gastrointestinal tract as well as other tissues and organs. AQP regulators can prevent and treat most gastrointestinal-related diseases, such as colorectal cancer, gastric ulcer, and gastric cancer. Although recent studies have proposed clinically relevant AQP-targeted therapies, such as the development of AQP inhibitors, clinical trials are still lacking and there are many difficulties. Traditional Chinese medicine (TCM) has been used in China for thousands of years to prevent, treat and diagnose diseases, and is under the guidance of Chinese medicine (CM) theory. Herein, we review the latest research on the regulation of AQPs by TCMs and their active components, including Rhei Radix et Rhizoma, Atractylodis macrocephalae Rhizoma, Salviae miltiorrhizae Radix et Rhizoma, Poria, Astragali radix, and another 26 TCMs, as well as active components, which include the active components include anthraquinones, saponins, polysaccharides, and flavonoid glycosides. Through our review and discussion of numerous studies, we attempt to explore the regulatory effects of TCMs and their active components on AQP expression in the corresponding parts of the body in terms of the Triple Energizer concept in Chinese medicine defined as "upper energizer, middle energizer, and lower energizer,"so as to offer unique opportunities for the development of AQP-related therapeutic drugs for digestive system diseases.

Regulation of transient receptor potential channels by traditional Chinese medicines and their active ingredients.

In recent years, activation of thermal transient receptor potential (TRP) ion channels at a range of temperatures has received widespread attention as a target for traditional Chinese medicine (TCM) to regulate body temperature and relieve pain. Discovery of transient receptor potential vanilloid 1 (TRPV1) was awarded a Nobel Prize, reflecting the importance of these channels. Here, the regulatory effects of TCMs and their active ingredients on TRP ion channels are reviewed, and future directions for research on the cold, hot, warm, cool, and neutral natures of TCMs are considered. In herbs with cold, hot, warm, cool, and neutral natures, we found 29 TCMs with regulatory effects on TRP ion channels, including Cinnamomi Cortex, Capsici Fructus, Rhei Radix et Rhizoma, Macleayae cordatae Herba, Menthae Haplocalycis Herba, and Rhodiolae Crenulatae Radix et Rhizoma. Although some progress has been made in understanding the regulation of TRP ion channels by TCMs and their ingredients, the molecular mechanism by which TCMs have this effect remains to be further studied. We hope this review will provide a reference for further research on the cold, hot, warm, cool, and neutral natures of TCMs.

A Chinese classical prescription Guizhi-Fuling Wan in treatment of ovarian cancer: An overview.

Ovarian cancer is one of the three most common female reproductive system cancers and has been a hot topic in the field of gynecology and oncology. Currently, surgery with chemotherapy is the common strategy in treatment of ovarian cancer, while it is always accompanied by drug resistance and some adverse effects. Over the past few years, traditional Chinese medicine (TCM) has been embraced by a large population of clinicians and researchers due to its high efficiency, low toxicity and minor side effects. Guizhi-Fuling Wan as a classical TCM formula has manifested certain efficacy in treating ovarian cancer. This article intends to further study the role and mechanism of Guizhi-Fuling Wan in treatment of ovarian cancer and explore the effective chemical components contained in the herbs of the formula. To this end, we reviewed the previous clinical studies and experiments to analyze the molecular mechanisms, pharmacological effects, active chemical components and their targets of action in treatment of ovarian cancer, thereby providing a theoretic basis for future studies and practices.

Stachydrine hydrochloride ameliorates cardiac hypertrophy through CaMKII/HDAC4/MEF2C signal pathway.

Stachydrine hydrochloride (Sta), an activated alkaloid, is isolated from traditional Chinese medicine Yimucao. In previous studies, the cardioprotective effects of Sta were found in our laboratory. However, the underling mechanisms of Sta is not fully elucidated. The aim of this study was to provide a detailed account of the anti-hypertrophic effects of Sta on transcriptional regulation. In vivo, C57BL/6J mice were subjected to transverse aortic constriction (TAC) and were orally treated with Sta. Morphological assessments, echocardiographic parameters, histological analyses and immunofluorescence were used to evaluate cardiac hypertrophy. In vitro, cardiomyocytes were stimulated by phenylephrine (PE), and cell surface and hypertrophy markers were tested by immunofluorescence and real-time polymerase chain reaction (RT-PCR). Moreover, western blotting, RT-PCR and luciferase reporter genes were used to assess the expression of proteins, mRNA and the activity of the CaMKII/HDAC4/MEF2C signal pathway in vivo and in vitro. We found that Sta blocked cardiac hypertrophy induced by pressure overload. We also demonstrated that Sta inhibited nuclear export or promoted nuclear import of HDAC4 through regulation of p-CaMKII, and it further improved the repression of MEF2C. Taken together, our findings demonstrated that Sta ameliorates cardiac hypertrophy through CaMKII/HDAC4/MEF2C signal pathway.

Research progress on classical traditional Chinese medicine Taohong Siwu decoction in the treatment of coronary heart disease.

The pathogenesis of coronary heart disease is closely related to blood stasis. Taohong Siwu decoction (THSW for short) is one of the most widely used prescriptions for activating blood and removing stasis. Clinical research has confirmed its curative effect on coronary heart disease. However, its underlying mechanism remains unclear. Therefore, this paper reviewed the clinical efficacy of THSW and determine its effective components based on a comprehensive literature review. Furthermore, the core components and targets of THSW in treating coronary heart disease using molecular docking were verified, and the interaction sites were predicted to construct a theoretical basis for the clinical application of THSW.

The multifaceted mechanisms of Paeoniflorin in the treatment of tumors: State-of-the-Art.

Paeoniflorin is a water-soluble monoterpenoid glycoside that can be derived from multiple herbaceous plants, such as Radix Paeoniae Rubra, Radix Paeoniae Alba, Paeonia suffruticosa and Cimicifugae Foetidae. Multiple studies have suggested that Paeoniflorin possesses an excellent anti-tumor effect in variety of tumors, including liver cancer, gastric cancer, breast cancer, lung cancer, pancreatic cancer, colorectal cancer and bladder cancer. It can induce cell apoptosis, inhibit proliferation, invasion and metastasis via different molecular mechanisms, which are mainly involved in nuclear transcription factor kappα (NF-κB), B-cell lymphoma-2(Bcl-2) family, MicroRNA, neural precursor cell expressed developmentally down-regulated protein 4(NEDD4) signaling pathway, transcription activating factor (STAT3), p21, p53/14-3-3 signaling pathway, transforming growth factor-ß1(TGF-ß1)/Smads signaling pathway, Mitogen-activated protein kinase (MAPK) signaling pathway and Notch-1. Current studies on anti-tumor effect and mechanism of action of Paeoniflorin remain unclear. Therefore, this study reviews the research progress in the anti-tumor effect and mechanism of Paeoniflorin in an attempt to provide a new thought and theoretical basis for further development and clinical application of Paeoniflorin.

Tiaojing Cuyun Recipe Enhances Pregnancy Outcome via the VEGF/PI3K/AKT/eNOS Signaling Pathway in EID Mice.

PURPOSE: In this study, we evaluated the effect of Tiaojing Cuyun Recipe (TJCYR) on embryo implantation dysfunction- (EID-) induced damage of endometrial receptivity in mice and investigated the mechanisms underlying the effect. METHODS: The main compounds of TJCYR were identified by high-performance liquid chromatography (HPLC). One hundred and twenty pregnant mice were randomly divided into six groups: control, EID only, progesterone (Prog)+EID, TJCYR-low-dose+EID, TJCYR-medium-dose+EID, and TJCYR-high-dose+EID. Mifepristone was injected to make the EID model. On the fourth day of pregnancy, serum was obtained to analyze hormone level by radioimmunoassay, the uterus was collected to analyze morphology by hematoxylin and eosin (H&E) and scanning electron microscopy (SEM), and a combination of immunofluorescence and Western blot was used to identify the related proteins. On the eighth day of pregnancy, the mice were sacrificed and the number of uterus-implanted blastocysts was counted. RESULTS: Treatment with TJCYR significantly improved the number of implanted sites, the number of well-developed pinopodes, and microvascular formation in the mice. Moreover, TJCYR significantly activated PI3K/Akt/eNOS signaling pathways to promote angiogenesis, resulting in significantly improved endometrial receptivity and fertility outcomes when compared to the model group. CONCLUSION: These findings demonstrate that TJCYR was able to protect embryo implantation of EID mice due to TJCYR-mediated improvement in endometrial receptivity by promoting endometrial angiogenesis.

Iron rich glauconite sand as an efficient phosphate immobilising agent in river sediments.

The reductive dissolution of iron (Fe) (oxy)hydroxides in sediments releases phosphorus (P) to the overlying water and may lead to eutrophication. Glauconite sands (GS) are rich in Fe and may be used as readily available P sorbents. This study was set up to test effects of dose and type of GS on the P immobilisation in sediments under hypoxic conditions. Three different GS were amended to a P-rich river sediment at doses of 0% (control), 5% and 10% (weight fractions) and incubated with overlying water in batch laboratory conditions. Glutamate was added to the solution after 15 days to deplete any residual dissolved oxygen from the sediment-water interface. In the first 15 days, the P concentration in the overlying water peaked to 1.5 mg P L-1 at day 9 in the control and decreased to 0.9 mg P L-1 at lowest Fe-dose and to 0.03 mg P L-1 at the highest Fe-dose, the effects of GS type and dose were explained by the Fe dose. After 15 days, the added glutamate induced a second, and larger peak of P in the overlying water in sediment, that peak was lower in amended sediments but no GS dose or type related effects were found. This suggests that freshly precipitated P species at the sediment-water interface can be remobilised. This study highlights the potential for using this natural mineral as a cheap and easily available sediment remediation material, but its longevity under rare extreme conditions needs to be further investigated.

Clinical application and pharmacological mechanism of Wuling powder in the treatment of ascites: A systematic review and network pharmacological analysis.

Ascites is one of the common complications in patients with decompensated liver cirrhosis and liver cancer. Wuling powder (WLP) is a classic prescription for the treatment of water retention caused by bladder gasification. It is also widely used in the treatment of ascites. This systematic review aimed to evaluate the clinical efficacy of WLP and determine its effective chemical components based on a large number of related pieces of literature. The pharmacological effects and chemical constituents of WLP were summarized. Besides, the clinical research status of WLP in the treatment of ascites caused by liver cancer and cirrhosis was analyzed. The key targets and pathways of WLP in the treatment of ascites based on network pharmacology analysis were also discussed. Furthermore, the core components and core targets of WLP in the treatment of ascites using molecular docking were verified and the interaction sites were predicted, to provide a theoretical and scientific basis for the clinical application of WLP.

Proteome Analysis of Camellia nitidissima Chi Revealed Its Role in Colon Cancer Through the Apoptosis and Ferroptosis Pathway.

Colon cancer is the third most common cancer in the world with a high mortality rate. At present, surgery combined with radiotherapy and chemotherapy is the primary treatment, but patient prognosis remains poor. Traditional Chinese medicine (TCM) has become a complementary and alternative source of anti-cancer drugs. Camellia nitidissima Chi (CNC) is a TCM used to treat a variety of cancers. However, the role of CNC in cancer remains elusive, and its effect and mechanism on colon cancer have not been reported. Here, we show that CNC exerts an excellent inhibitory effect on colon cancer proliferation and apoptosis induction in vitro and in vivo. We performed label free-based quantitative proteomic analysis to evaluate the HCT116 cells treated with CNC. Our data revealed a total of 363 differentially expressed proteins, of which 157 were up-regulated and 206 down-regulated. Gene Ontology enrichment analysis showed that these proteins were involved in tumor occurrence and development through multiple biological processes such as cell proliferation, cell apoptosis, cell cycle, and cell death. Interestingly, we also found significant changes in ferroptosis pathways. The role of essential proteins glutathione peroxidase 4 (GPX4) and heme oxygenase-1 (HMOX1) were verified. CNC decreased the expression of GPX4 and increased the expression of HMOX1 at the mRNA and protein levels in vivo and in vitro. Collectively, these findings reveal that CNC regulates colon cancer progression via the ferroptosis pathway and could be an attractive treatment for colon cancer.

Runjing Decoction alleviated cyclophosphamide-induced oligoasthenospermia rats by inhibiting cell apoptosis via RXFP1/AKT/FOXO1 pathway.

Runjing Decoction (RJD) is a prescription of traditional Chinese medicine for the treatment of oligoasthenospermia. However, the molecular mechanism of RJD on oligoasthenospermia still remains unknown. A model of oligoasthenospermia was induced in 30 Sprague Dawley rats by intraperitoneal injection of cyclophosphamide at 35 mg/kg per day for 5 days and treated by intragastric RJD (13.5 g/kg) or L-carnitine (100 mg/kg) for 14 days. The body weight, testis and epididymis weight, grade A spermatozoa, grade B spermatozoa, the percentage of sperm forward motility (PR%), the sperm activity rate and the sperm density of rats were evaluated before and after RJD treatment. The testis apoptosis was determined by TUNEL staining. The expressions of RXFP1, FoxO1, PI3K, Akt, Bax and Bcl-2 were determined by qRT-PCR and Western blot, respectively. After RJD treatment, the grade A spermatozoa, sperm PR%, sperm activity and sperm density were significantly increased relative to those in model rats. Cell apoptosis of testis tissue was reversed by RJD. RJD suppressed cell apoptosis, inhibited the expression of RXFP1, FOXO1, PI3K, AKT and Bax, and promoted the expression levels of Bcl-2 in testicular tissue of oligoasthenospermia rats. RJD could alleviate sperm quality and testis damage in oligoasthenospermia rats by inhibiting RXFP1/AKT/FOXO1 pathway.

Internal loading of phosphate in rivers reduces at higher flow velocity and is reduced by iron rich sand application: an experimental study in flumes.

Many lowland regions are afflicted with high phosphorus (P) peaks in rivers during the summer months. Static incubations of sediments have shown that reductive dissolution of ferric iron (Fe(III)) minerals in the sediment explain these P peaks. This study was set up to identify if that mechanism also dominates in a dynamic system, thereby testing the roles of water flow velocity and sediment Fe/P ratio. Decreasing flow velocity was suspected to lower the flux of dissolved oxygen (DO) towards the sediment. The role of the Fe(III)/P ratio was tested by amending iron-rich glauconite sand (GS) to the sediment, in this manner testing possible remediation techniques. Eight flumes (1.80 m long) were constructed with duplicates of four treatments of two laminar flow velocities over the sediment (0.05 m s-1 or 0.15 m s-1) that was either or not amended with GS (10% w/w). In all flumes a daily dose of sodium glutamate was added as a carbon source to mimic wastewater with high BOD, the flumes were operated for 28 days. A decreased velocity lowered the steady-state DO concentration and enhanced the sediment-water release of P by a factor 3. Sediment amendment with GS reduced solution P by factors 3 (low flow velocity) and 2 (high flow velocity). This effect is related to a combination of increasing binding sites for P and of lowering the DO consumption. These experimental data suggest that previously unexplained summer peaks of P in lowland rivers are related to low flow events that limit the DO flux. The internal loading of P requires management of DO in water and can be mitigated by enhancing sediment Fe.

A Highly Specific Multiple Enhancement Theranostic Nanoprobe for PET/MRI/PAI Image-Guided Radioisotope Combined Photothermal Therapy in Prostate Cancer.

An integrated molecular probe for combined tumor-targeted multimodal imaging and therapy in the era of precision medicine requires a multiplexed platform that simultaneously has high targeting specificity, versatile conjugation capability, and biocompatibility. Here, a novel biocompatible melanin nanoprobe (PMNs-II-813) coupled with a highly specific prostate-specific membrane antigen small molecule inhibitor is developed for the targeted multimodal diagnosis and treatment of prostate cancer. The melanin nanoparticles demonstrate photoacoustic imaging and photothermal therapy (PTT) functionalities via strong near-infrared absorption. The imaging contrast agents 89 Zr and Mn2+ are stably conjugated to the nanoparticles for positron emission tomography (PET) and magnetic resonance imaging (MRI). Fusion PET/MRI with PMNs-II-813 enables the monitoring of treatment effects in real time and lasts for more than 1 week, demonstrating the capability for multimodal theranostics in prostate cancer. Labeling with a therapeutic radionuclide, 131 I, simultaneously endows the nanoprobe with the capability for radioisotope therapy (RIT) and PTT under triple-modal imaging guidance. Combined PTT and RIT has an inhibitory effect on prostate cancer growth (tumor inhibition rate of ≈93% 20 days after treatment), which is significantly better than that with the single treatment. Overall, it is believed that PMNs-II-813 has potential for clinical translation to treat prostate cancer.

Efficacy and Safety Evaluation of Taohong Siwu Decoction () for Patients with Angina Pectoris: A Meta-Analysis of Randomized Controlled Trials.

OBJECTIVE: To assess the efficacy and safety of Taohong Siwu Decoction (, TSD), a Chinese herbal compound prescription, in patients with angina pectoris (AP). METHODS: Randomized clinical trials (RCTs) comparing TSD plus conventional treatment (CT) with CT plus placebo or CT only in the patients with AP were searched in PubMed, Cochrane Library, Excerpta Medica Database, Chinese National Knowledge Infrastructure, Chinese Biomedical Literature Database, Wanfang Database, Chinese Scientific Journal Database, Chinese Clinical Trial Registry and International Clinical Trial Registry from their inception to March 2017. The primary outcomes include a composite event of death, acute myocardial infarction (AMI), and target vessel revascularization. The secondary outcomes include angina symptom, electrocardiogram (ECG) improvement and serum high-sensitivity C-reactive protein (hs-CRP), endothelin-1 (ET-1), triglycerides (TG), total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels. The methodological quality of included studies and extracted available data were assessed. RevMan 5.3 software was used to conduct statistical analysis. The relative risk (RR) and standardized mean difference (SMD) with 95% confidence interval (CI) was calculated. A funnel plot was used to evaluate the publication bias. RESULTS: Among 204 studies identified in the literature search, 12 trials including 959 patients with AP met the inclusion criteria. No studies reported the primary outcome including death, AMI and target vessel revascularization. TSD combined with CT showed significant improvement in relieving angina symptom [RR=3.70, 95% CI (2.42, 5.67)] and ECG [RR=3.20, 95% CI (2.20, 4.65)] compared with CT alone. TSD combined with CT reduced the serum hs-CRP, TG, TC and LDL-C levels compared with CT alone. No serious adverse events were reported in TSD combined with CT. CONCLUSIONS: TSD combined with CT has a potential benefit on relieving AP without significant adverse events. However, the efficacy on the cardiovascular events needs to be assessed by more rigorously-designed, largescale, and multi-center RCTs in future.