Fabrication of hyaluronic acid-altered gold complex delivery for head and neck squamous cell carcinoma therapy with high antitumor efficacy and low in vivo toxicity.

The use of multifunctional nanomedicines in the treatment of tumors is gaining popularity. Here, we constructed a nanodrug delivery system (HA/Au-PDA@CZT) that targets tumors and responds to pH and near-infrared (NIR) dual stimuli. By precisely interacting with an overexpressed CD44 receptor in specific cancer cells, hyaluronic acid (HA) is coated on the Au-PDA NP surface for tumor-targeting abilities. When exposed to NIR radiation, polydopamine (PDA) and gold nanoshells exhibit exceptional photothermal performance that has the potential to both accelerate and kill HLAC 78 head and neck squamous cell carcinoma cells. Antitumor investigations conducted in vivo and in vitro demonstrated that nanomedicine had remarkable synergistic benefits with chemotherapy and photothermal treatment. Only 25.2% of the cells in the HA/Au-PDA@CZT with a NIR irradiation group were viable. Any group's lowest tumor volume was shown in the tumor mice subjected to HA/Au-PDA@CZT with NIR at 0.3 ± 0.1. Consequently, for synergistic chemo-photothermal therapy, our logically designed nanoplatform would be the potential for a head and neck squamous tumor-targeting drug delivery system.

Transferrin-Modified Triptolide Liposome Targeting Enhances Anti-Hepatocellular Carcinoma Effects.

Triptolide (TP) is an epoxy diterpene lactone compound isolated and purified from the traditional Chinese medicinal plant Tripterygium wilfordii Hook. f., which has been shown to inhibit the proliferation of hepatocellular carcinoma. However, due to problems with solubility, bioavailability, and adverse effects, the use and effectiveness of the drug are limited. In this study, a transferrin-modified TP liposome (TF-TP@LIP) was constructed for the delivery of TP. The thin-film hydration method was used to prepare TF-TP@LIP. The physicochemical properties, drug loading, particle size, polydispersity coefficient, and zeta potential of the liposomes were examined. The inhibitory effects of TF-TP@LIP on tumor cells in vitro were assessed using the HepG2 cell line. The biodistribution of TF-TP@LIP and its anti-tumor effects were investigated in tumor-bearing nude mice. The results showed that TF-TP@LIP was spherical, had a particle size of 130.33 ± 1.89 nm and zeta potential of -23.20 ± 0.90 mV, and was electronegative. Encapsulation and drug loading were 85.33 ± 0.41% and 9.96 ± 0.21%, respectively. The preparation was stable in serum over 24 h and showed biocompatibility and slow release of the drug. Flow cytometry and fluorescence microscopy showed that uptake of TF-TP@LIP was significantly higher than that of TP@LIP (p < 0.05), while MTT assays indicated mean median inhibition concentrations (IC50) of TP, TP@LIP, and TF-TP@ of 90.6 nM, 56.1 nM, and 42.3 nM, respectively, in HepG2 cell treated for 48 h. Real-time fluorescence imaging indicated a significant accumulation of DiR-labeled TF-TP@LIPs at tumor sites in nude mice, in contrast to DiR-only or DiR-labeled, indicating that modification with transferrin enhanced drug targeting to the tumor tissues. Compared with the TP and TP@LIP groups, the TF-TP@LIP group had a significant inhibitory effect on tumor growth. H&E staining results showed that TF-TP@LIP inhibited tumor growth and did not induce any significant pathological changes in the heart, liver, spleen, and kidneys of nude mice, with all liver and kidney indices within the normal range, with no significant differences compared with the control group, indicating the safety of the preparation. The findings indicated that modification by transferrin significantly enhanced the tumor-targeting ability of the liposomes and improved their anti-tumor effects in vivo. Reducing its distribution in normal tissues and decreasing its toxic effects suggest that the potential of TF-TP@LIP warrants further investigation for its clinical application.

[Discussion on "sugar needle - comfortable acupuncture and moxibustion"].

The cases of feeling comfort during acupuncture and moxibustion treatment in literature were summarized and its biological basis was explored. A simple classification of comfort was made, and the importance of obtaining comfort in acupuncture treatment was pointed out. Considering the pursuit of less pain and harmlessness in modern clinical treatment, sugar needle should be advocated and popularized in current clinical practice of acupuncture and moxibustion.

Exploring the Role of Lycium barbarum Polysaccharide in Corneal Injury Repair and Investigating the Relevant Mechanisms through In Vivo and In Vitro Experiments.

Lycium barbarum polysaccharide (LBP) is the main active component of Fructus Lycii, exhibiting various biological activities. This study aims to explore the protective effects of LBP on human corneal epithelial cells (HCEC) and a rat corneal injury model. Potential target points for LBP improving corneal injury repair were screened from public databases, and functional and pathway enrichment analyses of core targets were conducted using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Rat corneal alkali burns and HCEC oxidative stress injury models were established, and the results were validated through slit lamp examination, HE staining, TUNEL assay, immunofluorescence, CCK-8 assay, flow cytometry, scratch assay, and qRT-PCR methods. In the context of database retrieval, identification of 10 LBP monosaccharide components and 50 corneal injury repair-related targets was achieved. KEGG pathway analysis suggested that LBP might regulate the IL-17 and TNF signaling pathways through targets such as JUN, CASP3, and MMP9, thereby improving corneal damage. In vivo and in vitro experimental results indicated that LBP could reduce the increase of inflammation index scores (p < 0.05), inflammatory cell density (p < 0.01), TUNEL-positive cells (p < 0.01), corneal opacity scores (p < 0.01), and expression of corneal stromal fibrosis-related proteins α-SMA, FN, and COL (p < 0.01) caused by chemical damage to rat corneas. LBP inhibited oxidative stress-induced decreases in cell viability (p < 0.001) and migration healing ability (p < 0.01) in HCECs, reducing apoptosis rates (p < 0.001), ROS levels (p < 0.001), and the expression of inflammatory factors TNF-α and IL-6 (p < 0.01). qRT-PCR results demonstrated that LBP intervention decreased the mRNA levels of JUN, CASP3, and MMP9 in H2O2-induced alkaline-burned corneas and HCECs (p < 0.01).The integrated results from network pharmacology and validation experiments suggest that the inhibitory effects of LBP on apoptosis, inflammation, and fibrosis after corneal injury may be achieved through the suppression of the TNF and IL-17 signaling pathways mediated by JUN, CASP3, and MMP9.

Carvacrol Treatment Reduces Decay and Maintains the Postharvest Quality of Red Grape Fruits (Vitis vinifera L.) Inoculated with Alternaria alternata.

In this study, we isolated and identified pathogenic fungi from the naturally occurring fruits of red grapes, studied their biological characteristics, screened fifteen essential oil components to find the best natural antibacterial agent with the strongest inhibitory effect, and then compared the incidence of postharvest diseases and storage potential of red grapes treated with two concentrations (0.5 EC50/EC50) of essential oil components (inoculated with pathogenic fungi) during storage for 12 d at room temperature. In our research, Alternaria alternata was the primary pathogenic fungus of red grapes. Specifically, red grapes became infected which caused diseases, regardless of whether they were inoculated with Alternaria alternata in an injured or uninjured state. Our findings demonstrated that the following conditions were ideal for Alternaria alternata mycelial development and spore germination: BSA medium, D-maltose, ammonium nitrate, 28 °C, pH 6, and exposure to light. For the best Alternaria alternata spore production, OA medium, mannitol, urea, 34 °C, pH 9, and dark conditions were advised. Furthermore, with an EC50 value of 36.71 µg/mL, carvacrol demonstrated the highest inhibitory impact on Alternaria alternata among the 15 components of essential oils. In the meantime, treatment with EC50 concentration of carvacrol was found to be more effective than 0.5 EC50 concentration for controlling Alternaria alternata-induced decay disease of red grapes. The fruits exhibited remarkable improvements in the activity of defense-related enzymes, preservation of the greatest hardness and total soluble solids content, reduction in membrane lipid peroxidation in the peel, and preservation of the structural integrity of peel cells. Consequently, carvacrol was able to prevent the Alternaria alternata infestation disease that affects red grapes, and its EC50 concentration produced the greatest outcomes.

The current status of old traditional medicine introduced from Persia to China.

Traditional Chinese medicine (TCM) includes over ten thousand herbal medicines, some of which were introduced from outside countries and territories. The Silk Road enabled the exchange of merchandise such as teas, silks, carpets, and medicines between the East and West of the Eurasia continent. During this time, the 'Compendium of Materia Medica' (CMM) was composed by a traditional medicine practitioner, Shizhen Li (1,518-1,593) of the Ming Dynasty. This epoch-making masterpiece collected knowledge of traditional medical materials and treatments in China from the 16th century and before in utmost detail, including the origin where a material was obtained. Of 1892 medical materials from the CMM, 46 came from Persia (now Iran). In this study, the basic information of these 46 materials, including the time of introduction, the medicinal value in TCM theory, together with the current status of these medicines in China and Iran, are summarized. It is found that 20 herbs and four stones out of the 46 materials are registered as medicinal materials in the latest China Pharmacopoeia. Now most of these herbs and stones are distributed in China or replacements are available but saffron, ferula, myrrh, and olibanum are still highly dependent on imports. This study may contribute to the further development, exchange, and internationalization of traditional medicine of various backgrounds in the world, given the barriers of transportation and language are largely eased in nowadays.

Increased Blood-Brain Barrier Permeability of the Thalamus Correlated With Symptom Severity and Brain Volume Alterations in Patients With Schizophrenia.

BACKGROUND: While direct in vivo data from patients is insufficient, cumulative evidence of microvascular dysfunction has shown that the blood-brain barrier (BBB) is disrupted in schizophrenia. In this study, we attempted to test the hypothesis that greater BBB permeability in patients with schizophrenia was associated with clinical characteristics and brain volumetric alterations using dynamic contrast-enhanced magnetic resonance imaging techniques. METHODS: Structural magnetic resonance imaging and dynamic contrast-enhanced magnetic resonance imaging data from 29 patients with schizophrenia and 18 age- and sex-matched control subjects were obtained. We calculated the volume transfer constant (Ktrans) value and compared the difference between the 2 groups. The regions with an abnormal Ktrans value were extracted as regions of interest (thalamus), and the correlations with clinical characteristics and gray matter volume were analyzed. RESULTS: The results revealed that Ktrans value of the bilateral thalamus was higher in the schizophrenia group as compared to the healthy control group (p < .001). There were significant positive correlations between thalamic mean Ktrans value with disease duration (p < .05) and symptom severity (p < .001). Analysis of the thalamic subregions revealed that BBB disruption was significant in the pulvinar, especially the medial pulvinar nucleus and lateral pulvinar nucleus (p < .001). The correlation between the Ktrans values and the corresponding volumes was negative for the whole brain, the thalamus, and the thalamic subregions. CONCLUSIONS: These results provide the first in vivo evidence of BBB disruption of thalamus in patients with schizophrenia and suggest that BBB dysfunction might contribute to the pathological brain structural alterations in schizophrenia.

Thoracoscopic Lobectomy versus Segmentectomy in the Treatment of Patients with Early-Stage Lung Cancer.

Objective: To assess the clinical efficacy of thoracoscopic lobectomy and segmentectomy in the treatment of patients with early-stage lung cancer. Methods: A total of 70 patients with early-stage non-small cell lung cancer who were treated in our hospital from April 2018 to May 2020 were recruited and assigned at a ratio of 1 : 1 to receive either segmentectomy (observation group) or lobectomy (control group). Outcome measures included clinical efficacy, surgery-related indicators, pulmonary function indicators (forced vital capacity (FVC) and forced expiratory volume in one second (FEV1)), postoperative complications, and recurrence and metastasis. Results: There was no significant difference in the clinical efficacy between the two groups (P > 0.05). Segmentectomy was associated with a longer operation time and shorter hospital stay compared to lobectomy (P < 0.05). There was no statistical significance in the amount of intraoperative blood loss and the number of lymph nodes dissected (P > 0.05). Segmentectomy resulted in significantly higher FVC and FEV1 levels in patients compared to lobectomy (P < 0.05). There was no significant difference in the incidence of postoperative complications between the two groups (P > 0.05). The two groups of patients were followed up for 12 months after the operation, and there was no recurrence or metastasis in either group. Conclusion: The two surgical methods have similar efficacy and safety profiles, but for the treatment of patients with early-stage lung cancer, thoracoscopic segmentectomy is associated with a shorter hospital stay and better protection of the lung function of patients compared to lobectomy.

Efficacy and Safety of Xiaoyao Recipe in the Treatment of Poststroke Depression: A Systematic Review and Meta-Analysis.

Background: Poststroke depression (PSD) is a common neuropsychiatric disorder that affects the disability, mortality, functional recovery, and quality of daily life of patients. Xiaoyao Recipe (XYR) is often used to treat PSD and has achieved good clinical effects, but it lacks reliable evidence. Objective: This study aims to evaluate the effectiveness and safety of XYR on PSD through meta-analysis. Methods: A comprehensive literature search was carried out in multiple databases, including PubMed, the Cochrane Library, Chinese Biomedical Literature Service System, China National Knowledge Infrastructure, Wanfang Database, VIP Database, and ClinicalTrials, from inception to July 1, 2021, to collect randomized controlled trials that applied XYR for patients with PSD. For a controlled trial, the search time limit was set from the time of the database's establishment to July 2021. Two experienced researchers independently screened the literature according to the inclusion and exclusion criteria, extracted data, evaluated the quality of the literature, and used RevMan 5.3 software for meta-analysis. Results: A total of 12 studies were included in this study, involving 882 patients with PSD who were hospitalized or outpatients. The meta-analysis results showed that the total effective rate (p < 0.00001) of the test group (XYR or XYR combined with antidepressants) after treatment was high; Hamilton's Depression Scale score (p < 0.000001), Scandinavian Stroke Scale score (p=0.004 < 0.05), and Barthel index (p < 0.00001) were improved; the incidence of adverse reactions (p < 0.00001) was low; and the serum serotonin content (p < 0.00001) was high. Conclusion: Compared with antidepressant drugs, XYR is more effective and safer in the treatment of PSD patients. However, more high-quality studies are needed to further support the above conclusions.

Shuttle-Shape Carrier-Free Platinum-Coordinated Nanoreactors with O2 Self-Supply and ROS Augment for Enhanced Phototherapy of Hypoxic Tumor.

The synergistic nanotheranostics of reactive oxygen species (ROS) augment or phototherapy has been a promising method within synergistic oncotherapy. However, it is still hindered by sophisticated design and fabrication, lack of a multimodal synergistic effect, and hypoxia-associated poor photodynamic therapy (PDT) efficacy. Herein, a kind of porous shuttle-shape platinum (IV) methylene blue (Mb) coordination polymer nanotheranostics-loaded 10-hydroxycamptothecin (CPT) is fabricated to address the abovementioned limitations. Our nanoreactors possess spatiotemporally controlled O2 self-supply, self-sufficient singlet oxygen (1O2), and outstanding photothermal effect. Once they are taken up by tumor cells, nanoreactors as a cascade catalyst can efficiently catalyze degradation of the endogenous hydrogen peroxide (H2O2) into O2 to alleviate tumor hypoxia. The production of O2 can ensure enhanced PDT. Subsequently, under both stimuli of external red light irradiation and internal lysosomal acidity, nanoreactors can achieve the on-demand release of CPT to augment in situ mitochondrial ROS and highly efficient tumor ablation via phototherapy. Moreover, under the guidance of near-infrared (NIR) fluorescent imaging, our nanoreactors exhibit strongly synergistic potency for treatment of hypoxic tumors while reducing damages against normal tissues and organs. Collectively, shuttle-shape platinum-coordinated nanoreactors with augmented ROS capacity and enhanced phototherapy efficiency can be regarded as a novel tumor theranostic agent and further promote the research of synergistic oncotherapy.

Daphnetin inhibits spinal glial activation via Nrf2/HO-1/NF-κB signaling pathway and attenuates CFA-induced inflammatory pain.

Daphnetin (7, 8-dihydroxycoumarin, DAPH), a coumarin derivative isolated from Daphne odora var., recently draws much more attention as a promising drug candidate to treat neuroinflammatory diseases due to its protective effects against neuroinflammation. However, itscontribution to chronic inflammatory pain is largely unknown. In the current work, we investigated the effects of DAPH in a murine model of inflammatory pain induced by complete Freund's adjuvant (CFA) and its possible underlying mechanisms. Our results showed that DAPH treatment significantly attenuated mechanical allodynia provoked by CFA. A profound inhibition of spinal glial activation, followed by attenuated expression levels of spinal pro-inflammatory cytokines, was observed in DAPH-treated inflammatory pain mice. Further study demonstrated that DAPH mediated negative regulation of spinal NF-κB pathway, as well as its preferential activation of Nrf2/HO-1 signaling pathway in inflammatory pain mice. This study, for the first time, indicated that DAPH might preventthe development of mechanical allodynia in mice with inflammatory pain. And more importantly, these data provide evidence for the potential application of DAPH in the treatment of chronic inflammatory pain.

Effect of dihydromyricetin on hepatic encephalopathy associated with acute hepatic failure in mice.

CONTEXT: Hepatic encephalopathy (HE) is a complex neuropsychiatric disease caused by liver failure. Dihydromyricetin (DMY) is a traditional medicine used to treat liver injury. OBJECTIVE: To investigate the effects of dihydromyricetin (DMY) on hepatic encephalopathy associated with acute hepatic failure mice models established by thioacetamide (TAA) exposure. MATERIALS AND METHODS: Female BALB/c mouse were randomly divided into control, DMY, TAA, and TAA + DMY groups (n = 8). The first two groups were intraperitoneally injected with saline or 5 mg/kg DMY, respectively. The last two groups were injected with 600 mg/kg TAA to establish HE models, and then the mice in the last group were treated with 5 mg/kg DMY. Neurological and cognition functions were evaluated 24 and 48 h after injection. Mice were sacrificed after which livers and brains were obtained for immunoblot and histopathological analysis, while blood was collected for the analysis of liver enzymes. RESULTS: In the TAA + DMY group, ALT and AST decreased to 145.31 ± 12.88 U/L and 309.51 ± 25.92 U/L, respectively, whereas ammonia and TBIL decreased to 415.67 ± 41.91 µmol/L and 3.31 ± 0.35 µmol/L, respectively. Moreover, MDA decreased to 10.74 ± 3.97 nmol/g, while SOD and GST increased to 398.69 ± 231.30 U/g and 41.37 ± 21.84 U/g, respectively. The neurological score decreased to 2.87 ± 0.63, and the number of GFAP-positive cells decreased to 41.10 ± 1.66. Furthermore, the protein levels of TNF-α, IL-6, and GABAA in the cortex decreased. CONCLUSIONS: We speculate that DMY can serve as a novel treatment for HE.

Longdan Xiegan Tang attenuates liver injury and hepatic insulin resistance by regulating the angiotensin-converting enzyme 2/Ang (1-7)/Mas axis-mediated anti-inflammatory pathway in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: The ancient Chinese herbal formula Longdan Xiegan Tang (LXT, also called Gentiana Longdancao Decoction to Drain the Liver) treats insulin resistance- and inflammation-associated liver injuries in clinical practice. AIM OF THE STUDY: To investigate the molecular mechanisms underlying LXT-elicited improvement of the liver injuries. MATERIALS AND METHODS: Male rats were co-treated with olanzapine (5 mg/kg) and LXT extract (50 and 500 mg/kg) for eight weeks. Blood parameters were determined enzymatically or by ELISA. Gene/protein expression was analyzed by Real-Time PCR, Western blot and/or immunohistochemistry. RESULTS: LXT attenuated olanzapine-induced liver injury manifested by hyperactivities of plasma alanine aminotransferase and aspartate aminostransferase, hyperbilirubinemia and hypoalbuminemia. Furthermore, LXT improved hepatic insulin resistance that was indicated by hyperinsulinemia, the increased HOMA-IR index, and hepatic over-phosphorylation of Ser307 in insulin receptor substrate (IRS)1, Ser731 in IRS2, Tyr607 in phosphoinositide 3-kinase p85α and Ser473 in AKT at baseline. Mechanistically, LXT inhibited olanzapine-triggered hepatic over-phosphorylation of both IκB kinase (IKK)α/ß and nuclear factor (NF)κB p65 proteins, and mRNA overexpression of tumor necrosis factor α, interleukin 6, interleukin 1ß and CD68. More importantly, LXT restored the decreases in angiotensin-converting enzyme 2 (ACE2) protein level, and its downstream targets Ang (1-7) content and Mas receptor expression. CONCLUSIONS: The present results demonstrate that LXT attenuates liver injury and hepatic insulin resistance by regulating the ACE2/Ang (1-7)/Mas axis-mediated anti-inflammatory pathway in rats. Our findings provide a better understanding of LXT for treatment of insulin resistance- and inflammation-associated liver injuries.

Comparative efficacy and safety of high-dose dual therapy, bismuth-based quadruple therapy and non-bismuth quadruple therapies for Helicobacter pylori infection: a network meta-analysis.

Helicobacter pylori (H. pylori) infection is associated with the development of multiple diseases. The eradication rate of H. pylori has gradually decreased, suggesting the need to discover more effective therapies. This study aimed to compare the effectiveness of first-line treatments including high-dose dual therapy (HDDT), bismuth-based quadruple therapy (BQT), sequential therapy (ST), concomitant therapy (CT) and hybrid therapy (HT) by network meta-analysis (NMA). A comprehensive search on PubMed, Embase, Cochrane Library and Web of Science, was performed from their inception to 1 September 2019. A network analysis of randomized controlled trials (RCTs) comparing first-line therapies were carried out using Stata 14.0 and Revman 5.2. Moreover, a sensitivity analysis was conducted by omitting non-Asian studies. Finally, 41 RCTs with 14 119 patients were included. The NMA showed that, in terms of eradication rate, ST for 10 days (ST-10) was significantly lower than CT for 10 or 14 days (CT ≥ 10). Sensitivity analysis among the Asian population showed that ST-10 denoted the lowest effectiveness among the interventions. The ranking results based on probability showed that HDDT ranked first for the eradication rate. As for adverse events, HDDT was significantly less than BQT and CT regardless of duration, while BQT for 14 days represented higher adverse events than ST, HT and CT ≥ 10. HDDT ranked first among the therapies. In conclusion, HDDT for 14 days appeared to be the most optimal first-line therapy for H. pylori among the Asian population with comparable efficacy and compliance but causing fewer adverse events.

The ancient Chinese formula Longdan Xiegan Tang improves antipsychotic-induced hyperprolactinemia by repairing the hypothalamic and pituitary TGF-ß1 signaling in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Antipsychotics often induce hyperprolactinemia. The transforming growth factor (TGF)-beta1 signaling in the pituitary and hypothalamus inhibits prolactin synthesis and secretion, and its impairment is implicated in neuropsychiatric disorders. Longdan Xiegan Tang (LXT) alone or together with antipsychotics have been used to treat various neuropsychiatric diseases and hyperprolactinemia-associated disorders. AIM OF THE STUDY: To investigate the effect of LXT on hyperprolactinemia and involvement of the TGF-beta1 signaling. MATERIALS AND METHODS: Male rats were co-administered with olanzapine (5 mg/kg) and LXT extract (50 and 500 mg/kg) (p.o., × 8 weeks). Plasma concentrations of prolactin and TGF-beta1 were determined by ELISA. Protein expression was analyzed by Western blot. RESULTS: Treatment of rats with LXT extract suppressed olanzapine-induced increase in plasma prolactin concentration and overexpression of pituitary and hypothalamic prolactin protein. Importantly, LXT restored olanzapine-induced decrease in protein expression of the key components of the TGF-beta1 signaling, TGF-beta1, type II TGF-beta receptor, type I TGF-beta receptor and phosphorylated SMAD3 in the pituitary and hypothalamus. Further, it antagonized downregulation of pituitary and hypothalamic dopamine D2 receptor (D2R) protein level, and inhibited pituitary estrogen receptor (ER) alpha and ERbeta protein expression. CONCLUSIONS: The present results suggest that LXT ameliorates antipsychotic-induced hyperprolactinemia in rats by repairing the pituitary and hypothalamic TGF-beta1 signaling possibly via D2R, ERs or/and other pathways. Our findings may also provide scientific elucidation for use of the ancient Chinese formula to treat the impaired TGF-beta1 signaling-associated neuropsychiatric disorders.

Matrine Reverses the Warburg Effect and Suppresses Colon Cancer Cell Growth via Negatively Regulating HIF-1α.

The Warburg effect is a peculiar feature of cancer's metabolism, which is an attractive therapeutic target that could aim tumor cells while sparing normal tissue. Matrine is an alkaloid extracted from the herb root of a traditional Chinese medicine, Sophora flavescens Ait. Matrine has been reported to have selective cytotoxicity toward cancer cells but with elusive mechanisms. Here, we reported that matrine was able to reverse the Warburg effect (inhibiting glucose uptake and lactate production) and suppress the growth of human colon cancer cells in vitro and in vivo. Mechanistically, we revealed that matrine significantly decreased the messenger RNA (mRNA) and protein expression of HIF-1α, a critical transcription factor in reprogramming cancer metabolism toward the Warburg effect. As a result, the expression levels of GLUT1, HK2, and LDHA, the downstream targets of HIF-1α in regulating glucose metabolism, were dramatically inhibited by matrine. Moreover, this inhibitory effect of matrine was significantly attenuated when HIF-1α was knocked down or exogenous overexpressed in colon cancer cells. Together, our results revealed that matrine inhibits colon cancer cell growth via suppression of HIF-1α expression and its downstream regulation of Warburg effect. Matrine could be further developed as an antitumor agent targeting the HIF-1α-mediated Warburg effect for colon cancer treatment.

Study on new artificial floating island removing pollutants.

In this study, two types of artificial floating islands (AFIs), group A (consists of 1# and 2# traditional AFIs with plant and soil) and group B (consists of 4# and 5# new-type AFIs with plant, substrate, and with luffa sponge and corncob hanging at the bottom), were constructed, respectively. The removal effects and degradation mechanisms of luffa sponge and corncob in group B were compared and investigated. Plant height, root growth, and packing degradation of the two types of AFIs were studied. Temperature, dissolved oxygen (DO), and pH on the decontamination effects of AFI were discussed. The results showed that group A and group B AFIs showed great significant differences in removal of CODCr, TN, NO3--N, NH4+-N, and TP (p < 0.05). The TP removal of group B was 92.8 ± 0.6%, and the TN removal and NO3--N removal were significantly higher than that of group A, which was 90.3 ± 0.8% and 96.0 ± 2.2%, respectively; The addition of luffa sponge and corncob could enhance the biodegradability of sewage and the nitrogen and phosphorus removal efficiency of group B. The plant growth height of group B planted with Lythrum salicaria was 2.36 times higher than that of group A. The effect of temperature on TP was significantly greater than that of TN, and both groups of AFIs presented continuous improvement capacities of TN and TP removal when the temperature was above 15 °C. Group B was observed with a lower pH range of 6.69~7.12, which was more suitable for denitrification than group A. The release of carbon source of 5#-corncob AFI was 2.51 times higher than 4#-luffa sponge AFI at the end of the experiment.

Chronic treatment with the modified Longdan Xiegan Tang attenuates olanzapine-induced fatty liver in rats by regulating hepatic de novo lipogenesis and fatty acid beta-oxidation-associated gene expression mediated by SREBP-1c, PPAR-alpha and AMPK-alpha.

ETHNOPHARMACOLOGICAL RELEVANCE: The modified Longdan Xiegan Tang (mLXT) has been used clinically for various neuropsychiatric disorders and liver diseases. The use of antipsychotics is associated with nonalcoholic fatty liver disease. AIM OF THE STUDY: To investigate the effect and underlying mechanisms of mLXT on antipsychotic-induced fatty liver. MATERIALS AND METHODS: The representative active components in the formula were identified and quantified by a HPLC method. Fatty liver in male rats was induced by olanzapine (5 mg/kg) (p.o., × 8 weeks), and the rats were co-treated with mLXT extract (50 and 500 mg/kg). Blood and liver variables were determined enzymatically or histologically. Gene/protein expression was analyzed by real-time PCR and Western blot. RESULTS: Treatment of rats with mLXT decreased olanzapine-induced increases in hepatic triglyceride content, cell vacuolar degeneration and Oil Red O-stained area, accompanied by suppression of olanzapine-stimulated hepatic mRNA and/or protein overexpression of sterol regulatory element-binding protein (SREBP)-1c, and its downstream lipogenic enzymes for de novo lipogenesis. Besides, mLXT also activated hepatic expression of peroxisome proliferator-activated receptor-alpha and its target genes associated with fatty acid beta-oxidation, phosphorylated Thr172 in AMP-activated protein kinase (AMPK)-alpha (the upstream enzyme of SREBP-1c and PPAR-alpha), and its ratio to total AMPK-alpha. CONCLUSIONS: The present results suggest that chronic treatment with mLXT ameliorates olanzapine-induced fatty liver by regulating hepatic de novo lipogenesis- and fatty acid beta-oxidation-associated gene expression mediated by SREBP-1c and PPAR-alpha, respectively, through activation of AMPK-alpha. Our findings provide the evidence that supports clinical use of the formula for antipsychotic medication-induced fatty liver.

Low toxicity and accumulation of zinc oxide nanoparticles in mice after 270-day consecutive dietary supplementation.

The toxicity and accumulation of zinc oxide nanoparticles (ZnO-NPs), ZnO microparticles (ZnO-MPs) and Zn ions were evaluated after long-term feeding with zinc-replenished food (1600 mg zinc equivalent per kg food) for 270 consecutive days. It was difficult for ZnO-NPs, ZnO-MPs and Zn ions were difficult to pass through the intestine barrier, and most of them were excreted mainly through feces. The distribution results showed that there was no noticeable difference among the distribution profiles of ZnO-NPs, ZnO-MPs and Zn ions in mice. Zn accumulated only in the digestive tract organs after the exposure to all three samples. However, the biomedical parameters and pathological investigations showed liver lesions induced by ZnO-MPs, but fewer by ZnO-NPs or Zn ions. The reason for the remarkably low in vivo toxicity of ZnO-NPs is discussed. Our findings suggest that ZnO-NPs are relatively biocompatible as the nutritional additive at the commonly used dose.

Lanthanide (Gd(3+) and Yb(3+)) functionalized gold nanoparticles for in vivo imaging and therapy.

Nanoparticles are regularly used as contrast agents in bioimaging. Unlike other agents such as composite materials, nanoparticles can also be used for treating as well as imaging disease. Here we synthesized lanthanide functionalized gold nanoparticles that can be used for both imaging and therapy in vivo. That is a multifunctional nanoplatform was developed based on a simple and versatile method, by incorporating 10-nm gold nanoparticles and lanthanide ions (Gd(3+) and Yb(3+)), denoted as LnAu nanoparticles hereby. The LnAu nanoparticles were then surface-modified using a PEGylated amphiphilic polymer (C18MH-mPEG), and the resulting PEG modified LnAu nanoparticles (PEG-LnAu) display good monodispersion in water and good solubility in biological media. Due to the low toxicity in vitro and in vivo (as determined by a cell viability assay and histological and serum biochemistry analysis), the PEG-LnAu nanoparticles can be successfully applied to in vivo magnetic resonance imaging (MRI), in vivo computed tomography (CT) imaging and photothermal therapy (PTT) for tumor-bearing mice. Therefore, the present work developed an easy yet powerful strategy to combine lanthanide ions and gold nanoparticles to a unified nanoplatform for integrating bioimaging and therapy.