Photothermal Therapy Mediated Hybrid Membrane Derived Nano-formulation for Enhanced Cancer Therapy.

Emodin is applied as an antitumor drug in many tumor therapies. However, its pharmacology performances are limited due to its low solubility. Herein, we fused erythrocyte and macrophage to form a hybrid membrane (EMHM) and encapsulated emodin to form hybrid membrane-coated nanoparticles. We employed glycyrrhizin to increase the solubility of emodin first and prepared the hybrid membrane nanoparticle-coated emodin and glycyrrhizin (EG@EMHM NPs) which exhibited an average particle size of 170 ± 20 nm and encapsulation efficiency of 98.13 ± 0.67%. The half-inhibitory concentrations (IC50) of EG@EMHM NPs were 1.166 µg/mL, which is half of the free emodin. Based on the photosensitivity of emodin, the reactive oxygen species (ROS) results disclosed that ROS levels of the photodynamic therapy (PDT) section were higher than the normal section (P < 0.05). Compared to the normal section, PDT-mediated EG@EMHM NPs could induce an early stage of apoptosis of B16. The western blot and flow cytometry results verified that PDT-mediated EG@EMHM NPs can significantly improve the solubility of emodin and perform a remarkably antitumor effect on melanoma via BAX and BCL-2 pathway. The application of the combined chemical and PDT therapy could provide an improving target therapy for cutaneous melanoma and also may offer an idea for other insoluble components sources of traditional Chinese medicine. Schematic of EG@EMHM NPs formulation.

Microfluidic fabricated bisdemethoxycurcumin thermosensitive liposome with enhanced antitumor effect.

Bisdemethoxycurcumin (BDMC) is the main active ingredient that is isolated from Zingiberaceae plants, wherein it has excellent anti-tumor effects. However, insolubility in water limits its clinical application. Herein, we reported a microfluidic chip device that can load BDMC into the lipid bilayer to form BDMC thermosensitive liposome (BDMC TSL). The natural active ingredient glycyrrhizin was selected as the surfactant to improve solubility of BDMC. Particles of BDMC TSL had small size, homogenous size distribution, and enhanced cultimulative release in vitro. The anti-tumor effect of BDMC TSL on human hepatocellular carcinomas was investigated via 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide method, live/dead staining, and flowcytometry. These results showed that the formulated liposome had a strong cancer cell inhibitory, and presented a dose-dependent inhibitory effect on migration. Further mechanistic studies showed that BDMC TSL combined with mild local hyperthermia could significantly upregulate B cell lymphoma 2 associated X protein levels and decrease B cell lymphoma 2 protein levels, thereby inducing cell apoptosis. The BDMC TSL that was fabricated via microfluidic device were decomposed under mild local hyperthermia, which could beneficially enhance the anti-tumor effect of raw insoluble materials and promote translation of liposome.

The Synergy between Deep Learning and Organs-on-Chips for High-Throughput Drug Screening: A Review.

Organs-on-chips (OoCs) are miniature microfluidic systems that have arguably become a class of advanced in vitro models. Deep learning, as an emerging topic in machine learning, has the ability to extract a hidden statistical relationship from the input data. Recently, these two areas have become integrated to achieve synergy for accelerating drug screening. This review provides a brief description of the basic concepts of deep learning used in OoCs and exemplifies the successful use cases for different types of OoCs. These microfluidic chips are of potential to be assembled as highly potent human-on-chips with complex physiological or pathological functions. Finally, we discuss the future supply with perspectives and potential challenges in terms of combining OoCs and deep learning for image processing and automation designs.

Supplementary Feeding of Grazing Inner Mongolian Cashmere Goats during Pregnancy-Based on "Nutrient Requirements of Cashmere Goats".

This study aimed to conduct precise supplementation for pregnant cashmere goats under grazing based on the feeding standard. Eight Inner Mongolian pregnant cashmere goats of near-average body weight were selected at early gestation (44.41 ± 4.03 kg) and late gestation (46.54 ± 4.02 kg) to measure their nutrient intake. Then, two pregnant cashmere goat flocks, No. 10 (control group, on-farm supplement) and No. 11 (supplemented group, supplement based on standard), with the same goat herd structure and grassland type, were chosen to conduct the supplemental feeding experiment. The results showed that pregnant cashmere goats lacked daily the intake of dry matter, digestive energy, crude protein and most essential mineral elements under grazing. After supplemental feeding, the supplementation based on the feeding standard increased the cashmere length and cashmere length growth volume and decreased the cashmere fineness, with no statistical significance. The goat cashmere yield, goat weight after shearing, single and twin-birth kid weight and kids' mature secondary hair follicle density were significantly higher in the supplemented group (p < 0.05). In conclusion, supplementation in accordance with "Nutrient Requirements of Cashmere Goats" can enhance pregnant cashmere goats' fiber production, growth performance, fertility and kids' secondary hair follicles development, which is of great importance for the healthy and precise nutrition and management of cashmere goats.

Key Genes of Peripheral Blood Mononuclear Cells in Hepatocellular Carcinoma and Effective Chinese Herbs： A Bioinformatics Analysis and Systematic Review / 中国实验方剂学杂志

Objective:To explore the key gens of peripheral blood mononuclear cells in hepatocellular carcinoma（HCC-PBMC） and potentially effective Chinese herbs based on bioinformatics， and to verify the clinical efficacy of these Chinese herbs via a systematic review. Method:The chips GSE58208 and GSE36076 of HCC-PBMC were downloaded from the Gene Expression Omnibus （GEO）， followed by the identification of differentially expressed genes （DEGs） using RStudio. After protein-protein interaction （PPI） analysis by STRING， the DAVID was employed for gene ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment analysis. The DEGs of HCC-PBMC were visualized by Cytoscape. The key genes of HCC-PBMC were calculated by CytoHubba plug-in and mapped with those in Coremine Medical for screening out the potential Chinese herbs for the treatment of HCC， which were then included for subsequent systematic review. Result:A total of 203 DEGs were obtained （194 up-regulated and nine down-regulated）. As revealed by DAVID analysis， the DEGs were mainly enriched in such biological processes and signaling pathways as transcriptional regulation of DNA template， hydrolysis of ribonucleic acid phosphodiester bond， positive regulation of intranuclear mitosis and division， skeletal muscle fiber development， activation of mitogen-activated protein kinase（MAPK）activity， Fanconi anemia pathway， and metabolic pathway. The key genes of HCC-PBMC were calculated by Cytoscape to be<italic> </italic>GTPase IMAP family member 1 （GIMAP1）， GTPase IMAP family member 4 （GIMAP4）， GTPase IMAP family member 6 （GIMAP6）， GTPase IMAP family member 7 （GIMAP7）， GTPase IMAP family member 8 （GIMAP8）， interleukin-1<italic>β </italic>（IL-1<italic>β）</italic>， CX3C chemokine receptor 1 （CX3CR1）， C-C chemokine receptor type 2 （CCR2）， Toll-like receptor 7（TLR7）， and epidermal growth factor（EGF）. Through Coremine Medical analysis， it was concluded that Ginseng Radix et Rhizoma， Curcumae Longae Rhizoma， Centellae Herba， and Hedyotidis Herba were closely related to the key genes. Ginseng Radix et Rhizoma has the effects of tonifying and benefiting lung and spleen and enhancing strength， suitable for the liver depression and spleen deficiency syndrome or Qi-Yin deficiency syndrome of HCC. Hence， Si Junzitang with Ginseng Radix et Rhizoma as the sovereign medicinal was included for systematic review. It has been confirmed that Ginseng Radix Et Rhizoma was superior to western medicine alone in improving the overall clinical efficacy， alleviating TCM syndrome， elevating serum CD4⁺and CD4⁺/CD8⁺levels， and reducing the serum CD8⁺and TBIL levels （<italic>P</italic><0.01）， with high safety. Conclusion:This study conducted at the gene level has provided new ideas for clinical diagnosis and treatment of HCC. The systematic review of Ginseng Radix Et Rhizoma against HCC provides a basis for the clinical prevention and treatment of HCC with TCM.

Targeted Therapy against Metastatic Melanoma Based on Self-Assembled Metal-Phenolic Nanocomplexes Comprised of Green Tea Catechin.

The targeted therapy of metastatic melanoma is an important yet challenging goal that has received only limited attention to date. Herein, green tea polyphenols, (-)-epigallocatechin-3-gallate (EGCG), and lanthanide metal ions (Sm3+) are used as building blocks to engineer self-assembled SmIII-EGCG nanocomplexes with synergistically enhanced tumor inhibitory properties. These nanocomplexes have negligible systemic toxic effects on healthy cells but cause a significant reduction in the viability of melanoma cells by efficiently regulating their metabolic pathways. Moreover, the wound-induced migration of melanoma cells can be efficiently inhibited by SmIII-EGCG, which is a key criterion for metastatic melanoma therapy. In a mouse melanoma tumor model, SmIII-EGCG is directly compared with a clinical anticancer drug, 5-fluorouracil and shows remarkable tumor inhibition. Moreover, the targeted therapy of SmIII-EGCG is shown to prevent metastatic lung melanoma from spreading to main organs with no adverse side effects on the body weight or organs. These in vivo results demonstrate significant advantages of SmIII-EGCG over its clinical counterpart. The results suggest that these green tea-based, self-assembled nanocomplexes possess all of the key traits of a clinically promising candidate to address the challenges associated with the treatment of advanced stage metastatic melanoma.

Effect of Electroacupuncture on Spermatogenesis in Rats with Oligozoospermia of Insufficiency of Shen (Kidney) Essence Syndrome / 中国结合医学杂志

OBJECTIVE@#To assess the effect of electroacupuncture (EA) on expression of cytoskeletal proteins from Sertoli cells (SCs) and spermatogenesis in rats with oligozoospermia of insufficiency of Shen (Kidney) essence syndrome (OIKES).@*METHODS@#Twenty healthy male Sprague-Dawley rats were randomly assigned to four groups using a random number table: control, tripterygium glycosides (TG) treatment, sham and EA groups (n=5 in each group). A rat model of OIKES was established by oral gavage with TG. The EA group was treated with TG and received EA at Shenshu (BL 23) and Zusanli (ST 36) acupoints for 20 min, once daily for 30 days, while the sham group received EA at identical acupoints with skin penetration without stimulation. After 30 days, the final body weight and coefficients for the testis and epididymis were calculated and sperm parameters were measured. Immunohistochemical analyses were performed to detect expression of vimentin and α-tubulin in SCs and proliferating cell nuclear antigen (PCNA) immunoreactivity in germ cells. Apoptosis in germ cells was quantified by the transferase biotin-dUTP nick end labeling assay.@*RESULTS@#Compared with the control group, the final body weight and testis/epididymis coefficients of rats in the TG-treated group were not significantly different, but the sperm count and motility were lower (P<0.05). Expressions of vimentin and α-tubulin were also significantly weaker (P<0.01). The PCNA immunoreactivity of germ cells was decreased (P=0.059), whereas the apoptotic index of germ cells was increased significantly (P<0.01). In contrast, EA at BL 23 and ST 36 acupoints significantly improved the final body weight as well as the sperm count, concentration and motility (P<0.01 or P<0.05). EA increased expression of vimentin and α-tubulin in SCs markedly, and significantly enhanced PCNA immunoreactivity with decreased apoptosis in germ cells (P<0.01 or P<0.05).@*CONCLUSIONS@#EA at BL 23 and ST 36 acupoints has protective effects on spermatogenesis in rats with OIKES. This effect seems to be achieved by attenuating TG-induced disruption of cytoskeletal protein in SCs.

Discovery of a New Class of Cathepsin K Inhibitors in Rhizoma Drynariae as Potential Candidates for the Treatment of Osteoporosis.

Rhizoma Drynariae (RD), as one of the most common clinically used folk medicines, has been reported to exert potent anti-osteoporotic activity. The bioactive ingredients and mechanisms that account for its bone protective effects are under active investigation. Here we adopt a novel in silico target fishing method to reveal the target profile of RD. Cathepsin K (Ctsk) is one of the cysteine proteases that is over-expressed in osteoclasts and accounts for the increase in bone resorption in metabolic bone disorders such as postmenopausal osteoporosis. It has been the focus of target based drug discovery in recent years. We have identified two components in RD, Kushennol F and Sophoraflavanone G, that can potentially interact with Ctsk. Biological studies were performed to verify the effects of these compounds on Ctsk and its related bone resorption process, which include the use of in vitro fluorescence-based Ctsk enzyme assay, bone resorption pit formation assay, as well as Receptor Activator of Nuclear factor κB (NF-κB) ligand (RANKL)-induced osteoclastogenesis using murine RAW264.7 cells. Finally, the binding mode and stability of these two compounds that interact with Ctsk were determined by molecular docking and dynamics methods. The results showed that the in silico target fishing method could successfully identify two components from RD that show inhibitory effects on the bone resorption process related to protease Ctsk.

A 90-Day Feeding Study in Rats to Assess the Safety of Genetically Engineered Pork.

Our laboratory recently produced genetically engineered (GE) Meishan pigs containing a ZFN-edited myostatin loss-of-function mutant. These GE pigs develop and grow as normal as wild type pigs but produce pork with greater lean yield and lower fat mass. To assess any potential subchronic toxicity risks of this GE pork, a 90-day feeding study was conducted in Sprague-Dawley rats. Rats were randomly divided into five groups, and fed for 90 days with basic diet and basic diets formulated with low dose and high dose pork prepared from wild type pigs and GE pigs, respectively. Animal behaviors and clinical signs were monitored twice daily, and body weight and food consumption were measured and recorded weekly. At days 45 and 90, blood tests (lipid panel, electrolytes, parameters related to liver and kidney functions, and complete blood counts) were performed. Additionally, gross pathology and histopathological analyses were performed for major organs in each group. Data analysis shows that there were no significant differences in growth rate, food consumption, and blood test parameters between rat groups fed with GE pork and wild type pork. Although differences in some liver function parameters (such as aspartate aminotransferase, total proteins, albumin, and alkaline phosphatase) and white blood cell counts (such as lymphocyte percentage and monocyte percentage) were observed between rats fed with high dose GE pork and basic diet, all test results in rats fed with GE pork are in the normal range. Additionally, there are no apparent lesions noted in all organs isolated from rats in all five feeding groups on days 45 and 90. Overall, our results clearly indicate that food consumption of GE pork produced by ZFN-edited myostatin loss-of-function mutant pigs did not have any long-term adverse effects on the health status in rats.

Influential factors for anemia in pregnancy based on a nested case-control study in Changsha / 中南大学学报(医学版)

OBJECTIVE@#To explore the prevalence of anemia during pregnancy and the influential factors in changsha city, and to provide scientific evidence for prevention and intervention of anemia during pregnancy. 
@*METHODS@#A cluster sampling of 713 mothers, who delivered baby between January 1, 2013 and December 31, 2013 in the three streets of kaifu district of Changsha, was selected to establish a retrospective cohort. The maternal health information during pregnancy was collected within 15 days after the delivery. The influential factors of anemia during pregnancy were analyzed by the method of retrospective nested case-control study and conditional logistic regression.
@*RESULTS@#The prevalence of anemia during pregnancy in Changsha was 9.96%. The multiple conditional logistic regression results show that high family income (OR=0.632, P=0.020), high education level (OR=0.276, P=0.033), folic acid supplement (OR =0.248, P=0.050), iron supplement (OR=0.272, P<0.001) and eating blood products (OR=0.588, P=0.044) were the beneficial factors for anemia during pregnancy, while multipara (OR=2.917, P=0.003), long duration of menstrual period before pregnancy (OR=1.335, P=0.041), living in new decoration housing (OR=3.690, P=0.045) and tea-drinking (OR=1.365, P=0.094) were the risk factors for anemia during pregnancy. 
@*CONCLUSION@#The prevalence of anemia during pregnancy in Changsha is below the average levels. The occurrence of anemia during pregnancy is closely related to the women's economic level and nutritional status. Women should strengthen maternal nutrition during pregnancy and bedroom environment monitor, drink little strong tea and improve the nutritional status of iron during pregnancy.

Pericocins A-D, New Bioactive Compounds from Periconia sp.

One new dihydroisocoumarin, pericocin A (1), one new chromone, pericocin B (2), and two new α-pyrone derivatives, pericocins C-D (3-4), together with two known compounds, 3-(2-oxo-2H-pyran-6-yl)propanoic acid (5) and (E)-3-(2-oxo-2H-pyran-6-yl)acrylic acid (6), were isolated from the culture of the endolichenic fungus Periconia sp.. Their structures were elucidated by spectroscopic methods. All these compounds are derived from the polyketone biosynthetic pathway. Compound 1 was obtained as a mixture of enantiomers. The antimicrobial activity of compounds 1-5 was tested against Escherichia coli, Staphylococcus aureus, Aspergillus niger, and Candida albicans. Compounds 1-5 showed moderate antimicrobial activity against A. niger and weak activity against C. albicans.