A Hybrid Nanoadjuvant Simultaneously Depresses PD-L1/TGF-ß1 and Activates cGAS-STING Pathway to Overcome Radio-Immunotherapy Resistance.

Currently, certain cancer patients exhibit resistance to radiotherapy due to reduced DNA damage under hypoxic conditions and acquired immune tolerance triggered by transforming growth factor-ß1 (TGF-ß1) and membrane-localized programmed death ligand-1 (PD-L1). Meanwhile, cytoplasm-distributed PD-L1 induces radiotherapy resistance through accelerating DNA damage repair (DDR). However, the disability of clinically used PD-L1 antibodies in inhibiting cytoplasm-distributed PD-L1 limits their effectiveness. Therefore, a nanoadjuvant is developed to sensitize cancer to radiotherapy via multi-level immunity activation through depressing PD-L1 and TGF-ß1 by triphenylphosphine-derived metformin, and activating the cGAS-STING pathway by generating Mn2+ from MnO2 and producing more dsDNA via reversing tumor hypoxia and impairing DDR. Thus, Tpp-Met@MnO2@Alb effectively enhances the efficiency of radiotherapy to inhibit the progression of irradiated local and abscopal tumors and tumor lung metastases, offering a long-term memory of antitumor immunity without discernible side effects. Overall, Tpp-Met@MnO2@Alb has the potential to be clinically applied for overcoming radio-immunotherapy resistance.

Facile General Injectable Gelatin/Metal/Tea Polyphenol Double Nanonetworks Remodel Wound Microenvironment and Accelerate Healing.

Treating the most widespread complication of diabetes: diabetic wounds poses a significant clinical obstacle due to the intricate nature of wound healing in individuals with diabetes. Here a novel approach is proposed using easily applicable injectable gelatin/metal/tea polyphenol double nanonetworks, which effectively remodel the wound microenvironment and accelerates the healing process. The gelatin(Gel) crosslink with metal ions (Zr4+ ) through the amino acids, imparting advantageous mechanical properties like self-healing, injectability, and adhesion. The nanonetwork's biological functions are further enhanced by incorporating the tea polyphenol metal nanonetwork through in situ doping of the epigallocatechin gallate (EGCG) with great antibacterial, self-healing, antioxidant, and anticancer capabilities. The in vitro and in vivo tests show that this double nanonetworks hydrogel exhibits faster cell migration and favorable anti-inflammatory and antioxidant properties and can greatly reshape the microenvironment of diabetic wounds and accelerate the wound healing rate. In addition, this hydrogel is completely degraded after subcutaneous injection for 7 days, with nondetectable cytotoxicity in H&E staining of major mice organs and the serum level of liver function indicators. Considering the above-mentioned merits of this hydrogel, it is believed that the injectable gelatin/metal/tea polyphenol double nanonetworks have broad biomedical potential, especially in diabetic wound repair and tissue engineering.

An Immunomodulatory Hydrogel by Hyperthermia-Assisted Self-Cascade Glucose Depletion and ROS Scavenging for Diabetic Foot Ulcer Wound Therapeutics.

Current therapeutic protocols for diabetic foot ulcers (DFUs), a severe and rapidly growing chronic complication in diabetic patients, remain nonspecific. Hyperglycemia-caused inflammation and excessive reactive oxygen species (ROS) are common obstacles encountered in DFU wound healing, often leading to impaired recovery. These two effects reinforce each other, forming an endless loop. However, adequate and inclusive methods are still lacking to target these two aspects and break the vicious cycle. This study proposes a novel approach for treating DFU wounds, utilizing an immunomodulatory hydrogel to achieve self-cascade glucose depletion and ROS scavenging to regulate the diabetic microenvironment. Specifically, AuPt@melanin-incorporated (GHM3) hydrogel dressing is developed to facilitate efficient hyperthermia-enhanced local glucose depletion and ROS scavenging. Mechanistically, in vitro/vivo experiments and RNA sequencing analysis demonstrate that GHM3 disrupts the ROS-inflammation cascade cycle and downregulates the ratio of M1/M2 macrophages, consequently improving the therapeutic outcomes for dorsal skin and DFU wounds in diabetic rats. In conclusion, this proposed approach offers a facile, safe, and highly efficient treatment modality for DFUs.

Mild Hyperthermia-Assisted ROS Scavenging Hydrogels Achieve Diabetic Wound Healing.

Excessive reactive oxygen species (ROS) production induces oxidative damage to biomolecules, which can lead to the development of chronic diseases. Biocompatible hydrogel antioxidants composed of natural materials, such as polysaccharides and polyphenols, are of significant option for ROS scavenging. However, rapidly achieving hydrogel antioxidants with convenient, economical, safe, and efficient features remains challenging. Herein, facile synthesis of a physically cross-linked polyphenol/polysaccharide hydrogel by introducing tannic acid microsize particles (TAMP) into a cationic guar gum (CG) matrix is reported. Combining antioxidant/photothermal properties of TAMP and mechanical support from injectable CG, the formulated TAMP/CG is explored for treating diabetic wounds. Both in vitro and in vivo assays verify that TAMP/CG can protect the cells from ROS-induced oxidative damage, which can also be strengthened by the local photothermal heating (42 °C) triggered by near-infrared light. Overall, this study establishes the paradigm of enhanced diabetic wound healing by mild hyperthermia-assisted ROS scavenging hydrogels.

The flower head of Chrysanthemum morifolium Ramat. (Juhua): A paradigm of flowers serving as Chinese dietary herbal medicine.

ETHNOPHARMACOLOGICAL RELEVANCE: Dietary herbal medicines are widely used for the prevention and treatment of a variety of diseases due to their pharmacological activities in China. Juhua (the flower head of Chrysanthemum morifolium Ramat.), the most representative flower-derived one, which is mainly used for the treatment of respiratory and cardiovascular diseases, shows significant activities, such as antimicrobial, anti-inflammatory, and anticancer, and, neuroprotective, as well as effects on the cardiovascular system. AIMS OF THIS REVIEW: This review aims to provide an overview of the crucial roles of flowers in Chinese dietary herbal medicine, and the pharmaceutical research progress of Juhua (the paradigm of dietary herbal medicine derived from the flower) including its applications in Traditional Chinese medicine and diet, cultivars, phytochemistry, quality control, pharmacology, and toxicity, along with chrysanthemum breeding and biotechnology. METHOD: The information associated with Chinese dietary herbal medicine, flower-derived medicine, dietary flower, and pharmaceutical research of Juhua, was collected from government reports, classic books of Traditional Chinese medicine, the thesis of doctors of philosophy and maters, and database including Pubmed, Scifinder, Web of Science, Google Scholar, China National Knowledge Internet; and others. RESULT: All flower-originated crude medicines recorded in Chinese pharmacopeia and their applications were summarized for the first time in this paper. The edible history and development of flowers in China, the theory of Chinese dietary herbal medicines, as well as flowers serving as dietary herbal medicines, were discussed. Moreover, applications in Traditional Chinese medicine and diet, cultivars, phytochemistry, quality control, pharmacology, and safety evaluation of Juhua, together with chrysanthemum breeding and biotechnology, were summarized in this paper. CONCLUSION: The theory of dietary herbal medicines, which are an important part of the Traditional Chinese medicine system, has a history of thousands of years. Many herbal flowers, serving as dietary herbal medicines, contribute significantly to the prevention and treatment of a variety of diseases for Chinese people. To better benefit human health, more effective supervision practice for dietary herbal medicines is needed. Although various investigations on Juhua have been done, there is a lack of analytical methods for discrimination of cultivar flowers and identification of authenticity. Research on the major compounds with bioactivities, especially those related to its clinical application or healthcare function, as well as their possible mechanize, need be strengthened. More safety evaluation of Juhua should be carried out. The research limitations Juhua is facing exist in all dietary herbal medicine.

Multifunctional magnetic iron oxide nanoparticles: an advanced platform for cancer theranostics.

Multifunctional magnetic nanoparticles and derivative nanocomposites have aroused great concern for multimode imaging and cancer synergistic therapies in recent years. Among the rest, functional magnetic iron oxide nanoparticles (Fe3O4 NPs) have shown great potential as an advanced platform because of their inherent magnetic resonance imaging (MRI), biocatalytic activity (nanozyme), magnetic hyperthermia treatment (MHT), photo-responsive therapy and drug delivery for chemotherapy and gene therapy. Magnetic Fe3O4 NPs can be synthesized through several methods and easily surface modified with biocompatible materials or active targeting moieties. The MRI capacity could be appropriately modulated to induce response between T1 and T2 modes by controlling the size distribution of Fe3O4 NPs. Besides, small-size nanoparticles are also desired due to the enhanced permeation and retention (EPR) effect, thus the imaging and therapeutic efficiency of Fe3O4 NP-based platforms can be further improved. Here, we firstly retrospect the typical synthesis and surface modification methods of magnetic Fe3O4 NPs. Then, the latest biomedical application including responsive MRI, multimodal imaging, nanozyme, MHT, photo-responsive therapy and drug delivery, the mechanism of corresponding treatments and cooperation therapeutics of multifunctional Fe3O4 NPs are also be explained. Finally, we also outline a brief discussion and perspective on the possibility of further clinical translations of these multifunctional nanomaterials. This review would provide a comprehensive reference for readers to understand the multifunctional Fe3O4 NPs in cancer diagnosis and treatment.

Synthesis and pharmacological evaluation of naftopidil-based arylpiperazine derivatives containing the bromophenol moiety.

BACKGROUND: Prostate cancer (PCa) is the most common malignancy in men and in the absence of any effective treatments available. METHODS: For the development of potential anticancer agents, 24 kinds of naftopidil-based arylpiperazine derivatives containing the bromophenol moiety were synthesized and characterized by using spectroscopic methods. Their pharmacological activities were evaluated against human PCa cell lines (PC-3 and LNCaP) and a1-adrenergic receptors (a1-ARs; α1a, α1b, and α1d-ARs). The structure-activity relationship of these designed arylpiperazine derivatives was rationally explored and discussed. RESULTS: Among these derivatives, 3c, 3d, 3h, 3k, 3o, and 3s exhibited the most potent activity against the tested cancer cells, and some derivatives with potent anticancer activities exhibited better a1-AR subtype selectivity than others did (selectivity ratio > 10). CONCLUSION: This work provided a potential lead compound for the further development of anticancer agents for PCa therapy.

Glutamine Anabolism Plays a Critical Role in Pancreatic Cancer by Coupling Carbon and Nitrogen Metabolism.

Glutamine is thought to play an important role in cancer cells by being deaminated via glutaminolysis to α-ketoglutarate (aKG) to fuel the tricarboxylic acid (TCA) cycle. Supporting this notion, aKG supplementation can restore growth/survival of glutamine-deprived cells. However, pancreatic cancers are often poorly vascularized and limited in glutamine supply, in alignment with recent concerns on the significance of glutaminolysis in pancreatic cancer. Here, we show that aKG-mediated rescue of glutamine-deprived pancreatic ductal carcinoma (PDAC) cells requires glutamate ammonia ligase (GLUL), the enzyme responsible for de novo glutamine synthesis. GLUL-deficient PDAC cells are capable of the TCA cycle but defective in aKG-coupled glutamine biosynthesis and subsequent nitrogen anabolic processes. Importantly, GLUL expression is elevated in pancreatic cancer patient samples and in mouse PDAC models. GLUL ablation suppresses the development of KrasG12D-driven murine PDAC. Therefore, GLUL-mediated glutamine biosynthesis couples the TCA cycle with nitrogen anabolism and plays a critical role in PDAC.

Highly sensitive and selective light-up fluorescent probe for monitoring gallium and chromium ions in vitro and in vivo.

Over the past decades, gallium (Ga) compounds have gained importance in the field of cancer treatment. Gallium acts as an iron mimic and disturbs iron-dependent propagation and other processes in tumor cells. However, the toxicity of gallium was also well documented in vitro and in vivo in animals. Though the oral administration of gallium in humans is less toxic, it has also been shown that a long period of administration could induce tumor fibrosis. Chromium (Cr), a naturally occurring heavy metal, is commonly used in industrial processes and can cause severe health problems in humans. It has been found to be closely involved in the metabolism of nucleic acids, proteins and fats in humans. Cr(iii) salts can be used as micronutrients and dietary supplements. However, similar to gallium (Ga3+), chromium (Cr3+) can build up to an excessive degree that is harmful to the human body. Therefore, it would be of great interest to develop chemosensing for the selective and sensitive detection of gallium and chromium ions in vitro and in vivo. Herein, we reported that an NBD-based (4-chloro-7-nitrobenzo-2-oxa-1,3-diazole) fluorescent probe (NBDT) was fabricated with demonstrated extraordinary specificity and sensitivity. A swift response toward Ga3+ and Cr3+ ions was discovered using fluorescence enhancement over a wide pH range and with cycle stability. Furthermore, lighted up by Ga3+ and Cr3+ ions in vitro, this NBDT sensor was successfully applied to detect exogenous Ga3+ and Cr3+ ions in MDA-MB-231 and HepG2 cells. Additionally, using zebrafish as the in vivo model, we demonstrated the capability of this NBDT for detecting and imaging Ga3+ and Cr3+ ions in zebrafish. Taken together, this NBDT has indicated great potential for detecting and monitoring Ga3+ and Cr3+ ions in vitro and in vivo.

Investigation of parameters that determine Nano-DC vaccine transport.

Effective migration of dendritic cells into the lymphatic system organs is the prerequisite for a functional dendritic cell vaccine. We have previously developed a porous silicon microparticle (PSM)-based therapeutic dendritic cell vaccine (Nano-DC vaccine) where PSM serves both as the vehicle for antigen peptides and an adjuvant. Here, we analyzed parameters that determined dendritic cell uptake of PSM particles and Nano-DC vaccine accumulation in lymphatic tissues in a murine model of HER2-positive breast cancer. Our study revealed a positive correlation between sphericity of the PSM particles and their cellular uptake by circulating dendritic cells. In addition, the intravenously administered vaccines accumulated more in the spleens and inguinal lymph nodes, while the intradermally inoculated vaccines got enriched in the popliteal lymph nodes. Furthermore, mice with large tumors received more vaccines in the lymph nodes than those with small to medium size tumors. Information from this study will provide guidance on design and optimization of future therapeutic cancer vaccines.

Chemotherapy Sensitizes Therapy-Resistant Cells to Mild Hyperthermia by Suppressing Heat Shock Protein 27 Expression in Triple-Negative Breast Cancer.

Purpose: Triple-negative breast cancer (TNBC) is a clinically aggressive disease with poor prognosis. Conventional chemotherapeutics are generally able to shrink the tumor mass, but often fail to completely eradicate cancer stem-like cells (CSCs) that are responsible for high risk of relapse and frequent metastases. In this study, we examined thermal sensibility of CSCs, developed an approach that enabled concurrent elimination of both the bulk of cancer cells and CSCs, and investigated the underlying mechanism.Experimental Design: We designed a platform consisting of gold nanoparticle-coated porous silicon microparticle (AuPSM) that was also loaded with docetaxel micelles (mDTXs) to enable concurrent killing of the bulk of cancer cells by released mDTX and CSCs by mild hyperthermia upon stimulation of AuPSM with near infrared. In addition, we examined the role of heat shock proteins in sensitizing CSC killing. Finally, we applied mDTX-loaded AuPSM to treat mice with SUM159 and 4T1 orthotopic tumors and evaluated tumor growth and tumor metastasis.Results: MDA-MB-231 and SUM159 TNBC cells treated with mDTX-loaded AuPSM and mild hyperthermia displayed significantly reduced efficiencies in mammosphere formation than those treated with mDTX alone or mild hyperthermia alone. Combination treatment also completely inhibited SUM159 orthotopic tumor growth and 4T1 tumor metastasis. Mechanistically, DTX treatment suppressed expression of heat shock protein 27 in cancer cells including the CSCs, rendering cells sensitive to mild hyperthermia.Conclusions: Our results indicate that chemotherapy sensitizes CSC to mild hyperthermia. We have developed an effective therapeutic approach to eliminate therapy-resistant cells in TNBC. Clin Cancer Res; 24(19); 4900-12. ©2018 AACR.

Tetramethylpyrazine regulates breast cancer cell viability, migration, invasion and apoptosis by affecting the activity of Akt and caspase-3.

Tetramethylpyrazine (TMP), an effective component of the traditional Chinese medicine Chuanxiong Hort, has been proven to exhibit a beneficial effect in a number of types of malignant epithelial cancer. However, the mode of action of TMP on breast cancer cells remains unknown. The aim of the present study was to investigate the regulatory effect of TMP on breast cancer cells and its underlying molecular mechanism of action. Different concentrations of TMP were used to treat breast cancer cells, and subsequently, the effects on the viability, apoptosis, and migration and invasion abilities were determined. In addition, the expression and activity levels of the protein kinase B (Akt) signaling pathway and caspase-3 were explored via reverse transcription-quantitative polymerase chain reaction and western blot analysis. The results of the present study revealed that TMP significantly inhibited the viability, migration and invasion rates, and increased the apoptosis of MDA-MB-231 cells in a dose-dependent manner. The minimum effective dose was ~1,600 µM. Additional mechanistic studies demonstrated that 1,600 and 3,200 µM TMP significantly decreased the gene expression and activity of Akt and increased the activity of caspase-3. This mechanism may be responsible for the inhibition of viability, migration and invasion, and activation of apoptosis in breast cancer cells. The results of the present study suggested that TMP may be used in chemotherapy against breast cancer.

Suppression of human breast cancer cells by tectorigenin through downregulation of matrix metalloproteinases and MAPK signaling in vitro.

Breast cancer is a major life­threatening malignancy and is the second highest cause of mortality. The aim of the present study was to investigate the effects of tectorigenin (Tec), a Traditional Chinese Medicine, against human breast cancer cells in vitro. MDA­MB­231 and MCF­7 human breast cancer cells were treated with various concentrations of Tec. Cell proliferation was evaluated using the Cell Counting kit­8 assay, and apoptosis and the cell cycle were examined by flow cytometry. The migratory and invasive abilities of these cells were detected by Transwell and Matrigel assays, respectively. Metastasis­, apoptosis­ and survival­related gene expression levels were measured by reverse transcription­quantitative polymerase chain reaction and western blotting. The results indicated that Tec was able to inhibit the proliferation of MDA­MB­231 and MCF­7 cells in a dose­ and time­dependent manner. Furthermore, Tec treatment induced apoptosis and G0/G1­phase arrest, and inhibited cell migration and invasion. Tec treatment decreased the expression of matrix metalloproteinase (MMP)­2, MMP9, BCL­2, phosphorylated­AKT and components of the mitogen­activated protein kinase (MAPK) signaling pathway, and increased the expression of BCL­2­associated X, cleaved poly [ADP­ribose] polymerase and cleaved caspase­3. In conclusion, Tec treatment suppressed human breast cancer cells through the downregulation of AKT and MAPK signaling and the upregulated expression and/or activity of the caspase family in vitro. Therefore, Tec may be a potential therapeutic drug to treat human breast cancer.

Organophosphate Flame-Retardants Alter Adult Mouse Homeostasis and Gene Expression in a Sex-Dependent Manner Potentially Through Interactions With ERα.

Flame retardants (FRs) such as polybrominated diphenyl ethers and organophosphate FR (OPFR) persist in the environment and interact with multiple nuclear receptors involved in homeostasis, including estrogen receptors (ERs). However, little is known about the effects of FR, especially OPFR, on mammalian neuroendocrine functions. Therefore, we investigated if exposure to FR alters hypothalamic gene expression and whole-animal physiology in adult wild-type (WT) and ERα KO mice. Intact WT and KO males and ovariectomized WT and KO females were orally dosed daily with vehicle (oil), 17α-ethynylestradiol (2.5 µg/kg), 2,2', 4,4-tetrabromodiphenyl ether (BDE-47, 1 or 10 mg/kg), or an OPFR mixture {1 or 10 mg/kg of tris(1, 3-dichloro-2-propyl)phosphate, triphenyl phosphate, and tricresyl phosphate each} for 28 days. Body weight, food intake, body composition, glucose and insulin tolerance, plasma hormone levels, and hypothalamic and liver gene expression were measured. Expression of neuropeptides, receptors, and cation channels was differentially altered between WT males and females. OPFR suppressed body weight and energy intake in males. FR increased fasting glucose levels in males, and BDE-47 augmented glucose clearance in females. Liver gene expression indicated FXR activation by BDE-47 and PXR and CAR activation by OPFR. In males, OPFR increased ghrelin but decreased leptin and insulin independent of body weight. The loss of ERα reduced the effects of both FR on hypothalamic and liver gene expression and plasma hormone levels. The physiological implications are that males are more sensitive than ovariectomized females to OPFR exposure and that these effects are mediated, in part, by ERα.

Original Research: Effect of various dietary fats on fatty acid profile in duck liver: Efficient conversion of short-chain to long-chain omega-3 fatty acids.

Omega-3 fatty acids, especially long-chain omega-3 fatty acids, have been associated with potential health benefits for chronic disease prevention. Our previous studies found that dietary omega-3 fatty acids could accumulate in the meat and eggs in a duck model. This study was to reveal the effects of various dietary fats on fatty acid profile and conversion of omega-3 fatty acids in duck liver. Female Shan Partridge Ducks were randomly assigned to five dietary treatments, each consisting of 6 replicates of 30 birds. The experimental diets substituted the basal diet by 2% of flaxseed oil, rapeseed oil, beef tallow, or fish oil, respectively. In addition, a dose response study was further conducted for flaxseed and fish oil diets at 0.5%, 1%, and 2%, respectively. At the end of the five-week treatment, fatty acids were extracted from the liver samples and analyzed by GC-FID. As expected, the total omega-3 fatty acids and the ratio of total omega-3/omega-6 significantly increased in both flaxseed and fish oil groups when compared with the control diet. No significant change of total saturated fatty acids or omega-3 fatty acids was found in both rapeseed and beef tallow groups. The dose response study further indicated that 59-81% of the short-chain omega-3 ALA in flaxseed oil-fed group was efficiently converted to long-chain DHA in the duck liver, whereas 1% of dietary flaxseed oil could produce an equivalent level of DHA as 0.5% of dietary fish oil. The more omega-3 fatty acids, the less omega-6 fatty acids in the duck liver. Taken together, this study showed the fatty acid profiling in the duck liver after various dietary fat consumption, provided insight into a dose response change of omega-3 fatty acids, indicated an efficient conversion of short- to long-chain omega-3 fatty acid, and suggested alternative long-chain omega-3 fatty acid-enriched duck products for human health benefits.

Effects of dietary fats on egg quality and lipid parameters in serum and yolks of Shan Partridge Duck.

The effects of different dietary fats with variable levels of polyunsaturated fatty acids (PUFAs) on egg quality of Shan Partridge Duck, serum, and yolk lipid parameters were examined in this study. A flock of 585 optimal produced ducks were selected and diets enriched with 0.5%, 1%, or 2% fish oil (F)/flaxseed oil (FL)/rapeseed oil (R)/tallow (T) plus basal diet were supplied through a 28-d period. Supplemental fat source and fat level had no effects on egg qualities. Proportions of yolk total cholesterol (TC), saturated fatty acids (SFAs), monounsaturated fatty acids (MUFAs) were reduced (P < 0.001), while polyunsaturated fatty acids (PUFAs), ω-6 polyunsaturated fatty acids (n-6 PUFAs), ω-3 polyunsaturated fatty acids (n-3 PUFAs), Docosahexaenoic Acid (DHA), and Eicosapentaenoic Acid (EPA) were increased by fish oil, flaxseed oil, or rapeseed oil. Effects of supplementation increasing DHA and EPA were detected in F, FL, and R. Compared with C, fish oil significantly increased low-density lipoprotein cholesterol (LDL-C) in serum, flaxseed oil significantly reduced TC and increased very low-density lipoprotein cholesterol (VLDL-C), rapeseed oil significantly reduced TC and LDL-C in serum and increased VLDL-C, tallow significantly increased LDL-C. It is concluded that unsaturated fatty acids rich diets (fish oil, flaxseed oil, and rapeseed oil) might increase yolk PUFAs, reduce yolk cholesterol, and change serum lipid parameters without evident effect on egg qualities.

Hesperetin Liposomes for Cancer Therapy.

Hesperetin is a compound from citrus fruit that has previously been found to exert anticancer activity through a variety of mechanisms. However, the application of hesperetin to cancer therapy has been hampered by its hydrophobicity, necessitating the use of toxic solubilizing agents. Here, we have developed the first liposome-based delivery system for hesperetin. Liposomes were fabricated using the thin-layer evaporation technique and physical and pharmacological parameters were measured. The liposomes remained stable for prolonged periods of time in serum and under storage conditions, and displayed anticancer efficacy in both H441 lung cancer cells and MDA-MB-231 breast cancer cells. Furthermore, the anticancer activity was not impaired in cells expressing the multidrug resistance protein 1 (MDR-1). In conclusion, the encapsulation of hesperetin in liposomes does not interfere with therapeutic efficacy and provides a biocompatible alternative to toxic solubilizing agents, thereby enabling future clinical use of this compound for cancer therapy.

Multifunctional gold nanorods for siRNA gene silencing and photothermal therapy.

Cancer is a complex disease that usually requires several treatment modalities. A multifunctional nanotherapeutic system is designed, incorporating small interfering RNA (siRNA) and gold nanorods (Au NRs) for photothermal therapy. Surface-engineered Au NRs with polyethylenimine are synthesized using a layer-by-layer assembly and siRNA is absorbed on the surface. The siRNA is efficiently delivered into breast cancer cells, resulting in subsequent gene silencing. Cells are then irradiated with near-infrared (NIR) light, causing heat-induced anticancer activity. The combination of gene silencing and photothermal therapy results in effective inhibition of cell proliferation.

Identification of differentially expressed known and novel miRNAs in broodiness of goose.

MicroRNAs (miRNAs) are endogenous small noncoding RNAs plays a critical role in posttranscriptional regulation of gene expression. Broodiness is observed in most avian species and influences egg production. Several genes are known to play an important role in regulating the progress of reproduction. The goose is one of the most important waterfowls. However, the involvement of miRNAs in the broodiness behavior of Anser cygnoides (Swan Goose) is unknown. High-throughput sequencing and bioinformatics analysis were used to identify the miRNAs involved in egg-laying and brooding behavior of geese in our study. The results showed 38 up-regulated and 14 down-regulated known miRNAs/miRNA*s with reads>1,000 in at least one group and a fold change of >2.0, compared with those of the egg-laying group (P<0.001). We also identified 114 and 94 novel miRNAs in the broody and egg-laying groups, respectively. Of these, 4 novel miRNAs were differentially expressed between the two groups. The study showed the expression of small RNAs in goose reproduction and identified known and novel miRNAs regulated in broodiness. The results reveal that these differentially expressed miRNAs may be involved in broodiness of A. cygnoides.