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The 2 × 4 factorial experiment was designed to determine the effect of strain and photostimulation age on sexual maturity and reproductive performance of rooster breeders. A total of 96 White Leghorn (WL) and 120 Beijing You Chicken (BYC) roosters were randomly allocated to 4 treatments at 14 wk of age. The treatments represent photostimulation at 16, 18, 20, and 22 wk of age, respectively (PS16, PS18, PS20, and PS22), in both strains. Photostimulation was achieved by increasing the day length from 8L:16D to 14L:10D and by increasing lighting intensity from 10 lx to 80 lx. Three birds from each interaction were sacrificed to characterize the comb and testis weights at 4 time points: 1 d before photostimulation and 2, 4, and 6 wk after photostimulation. Semen quality and hatching performance with the semen of the experimental roosters were measured at 30 and 45 wk of age, respectively. Results showed that the testis weight of PS20 and PS22 in WL and BYC was 6.4- and 2.9-fold higher than that of PS18 before photostimulation, while testis weight of PS18 in both strains increased sharply after photostimulation. The diameter of seminiferous tubules increased in the photostimulated roosters as compared with the nonphotostimulated ones, and mature spermatozoa were produced 4 wk after photostimulation and at 20 wk of age for PS16. The WL had lower semen volume and total sperm count than BYC (P 0.05). In addition, semen quality traits were not affected by age at photostimulation (P > 0.05) in both strains. The fertility and hatching performance were not affected by strain or photostimulation age (P > 0.05). In summary, the sexual maturation of rooster breeders can be advanced by photostimulation at an early age, which does not lead to a difference in semen quality or hatching performance at adult stage.

Two essential oils were isolated from discarded perfume lemon and leaves (Citrus limon (L.) Burm. F.) by hydro-distillation with good yield (0.044% for perfume lemon and 0.338% for leaves). Their biological activities were evaluated against five selected bacterial strains and Aedes albopictus (Ae. albopictus, Diptera: Culicidae). Chemical composition indicated that both essential oils were rich in essential phytochemicals including hydrocarbons, monoterpenes and sesquiterpene. These constituents revealed some variability among the oils displaying interesting chemotypes (R)-(+)-limonene (12.29–49.63%), citronellal (5.37–78.70%) and citronellol (2.98–7.18%). The biological assessments proved that the two essential oils had similar effect against bacterial (inhibition zones diameter ranging from 7.27 ± 0.06 to 10.37 ± 0.15 mm; MICs and MBCs ranging from 1.6 to 6.4 mg/mL); against Ae. albopictus larvae (LC50 ranging from 384.81 to 395.09 ppm) and adult mosquito (LD50 ranging from 133.059 to 218.962 μg/cm2); the activity of the two chemotypes ((R)-(+)-limonene and citronellal): larvae (LC50 ranging from 267.08 to 295.28 ppm), which were all presented in dose-dependent manners. Through this work, we have showcased that recycling and reusing of agriculture by-products, such as discarded perfume lemon and leaves can produce eco-friendly alternatives in bacterial disinfectants and mosquito control product.

Glucitol-core containing gallotannins (GCGs) from the red maple (Acer rubrum) species have been reported to exhibit skin beneficial activities but their inhibitory effects on elastase remain unclear. Herein, we evaluated a series of GCGs for their anti-elastase activity, skin permeability, and cytoprotective effects in human keratinocytes HaCaT cells. GCGs’ anti-elastase effects were enhanced as their number of galloyl groups increased, which may be attributed to the formation of more stable protein–ligand complexes. In addition, GCGs were predicted to have moderate skin permeability and ginnalin A (GA) showed favorable permeability in the PAMPA model and cell uptake assay. Moreover, GA, ginnalin B, and maplexin F (at 50 µM) reduced H2O2-induced reactive oxygen species in HaCaT cells by 70.8, 92.8, and 84.6%, respectively. In conclusion, red maple GCGs are skin permeable elastase inhibitors with antioxidant activity, which may contribute to their overall skin beneficial effects and support their potential for cosmeceutical applications.

Introduction Postoperative ileus (POI), a common complication after surgery, severely affects postoperative recovery. It is unclear whether pretreatment with transcutaneous electrical acupoint stimulation (TEAS) can improve recovery from POI. This trial will evaluate the effects of pretreatment with TEAS on POI.Methods and analysis This will be a prospective, randomised controlled trial. American Society of Anesthesiologists (ASA) physical status classification I–III level patients, aged 18–75 years and scheduled for laparoscopic colon surgery, will be included in the study. It is planned that 146 subjects will be randomised to the TEAS and sham TEAS (STEAS) groups. The groups will undergo two sessions of TEAS/STEAS daily for 3 days before surgery, with a final TEAS/STEAS treatment 30 min before anaesthesia. The primary endpoint of the study will be time to first defaecation. Secondary endpoints will include time to first flatus, time to tolerance of oral diet, GI-2 (composite outcome of time to first defaecation and time to tolerance of oral diet), time to independent walking, length of hospital stay, postoperative pain Visual Analogue Scale score on the first 3 days after surgery, analgesic requirements, complications and plasma concentrations of interferon-β (IFN-β), IFN-γ, interleukin-6 (IL-6) and IL-1β. Multiple linear regression will be used to identify independent predictors of outcome measures.Ethics and dissemination This study has been approved by the Chinese Registered Clinical Trial Ethics Review Committee (No. ChiECRCT-20170084). The results of the trial will be published in an international peer-reviewed journal.Trial registration number This study has been registered with the Chinese Clinical Trial Registry (No. ChiCTR-INR-17013184).Trial status The study was in the recruitment phase at the time of manuscript submission.

Alzheimer's disease (AD) is a complex neurodegenerative disease characterized by cognitive dysfunction. Kai-Xin-San (KXS) is a traditional Chinese medicine (TCM) formula that has been used to treat AD patients for over a thousand years in China. However, the therapeutic mechanisms of KXS for treating AD have not been fully explored. Herein, we used a comprehensive network pharmacology approach to investigate the mechanism of action of KXS in the treatment of AD. This approach consists of construction of multiple networks and Gene Ontology enrichment and pathway analyses. Furthermore, animal experiments were performed to validate the predicted molecular mechanisms obtained from the systems pharmacology-based analysis. As a result, 50 chemicals in KXS and 39 AD-associated proteins were identified as major active compounds and targets, respectively. The therapeutic mechanisms of KXS in treating AD were primarily related to the regulation of four pathology modules, including amyloid beta metabolism, tau protein hyperphosphorylation process, cholinergic dysfunction, and inflammation. In scopolamine-induced cognitive dysfunction mice, we validated the anti-inflammatory effects of KXS on AD by determining the levels of inflammation cytokines including interleukin (IL)-6, IL-1β, and tumor necrosis factor (TNF)-α. We also found cholinergic system dysfunction amelioration of KXS is correlated with upregulation of the cholinergic receptor CHRNB2. In conclusion, our work proposes a comprehensive systems pharmacology approach to explore the underlying therapeutic mechanism of KXS for the treatment of AD.

To disclosed the internal factors for the growth of mycelium and Lentinus edodes, Quercus Linn wood, which was biotransformed during the artificial cultivation of Lentinus edodes, were synergistically characterized by TGA/DTG, FT-IR and NMR. The results showed that the different ingredients of hemicellulose decreased during steam explosion and biodegradation of Lentinus edodes, however hemicellulose content continued to increased. FT-IR showed that the transmittance of the characteristic peaks in hemicellose gradually increased after decreased after steam explosion and biodegradation of Lentinus edodes. TGA/DTG curves that thermal stability and maximum thermal degradation rates of hemicelloses were contiguous after steam explosion and biodegradation of Lentinus edodes. Structural determination based on FT-IR and 1H, and 2D-HSQC NMR analyses showed that the alkali-extractable hemicelluloses shared the structure composed of (1 → 4)-linked β-d-xylopyranosyl backbone with 4-O-methyl-R-d-glucuronic acid attached to O-2 of the xylose residues and l-arabinose attached to O-3 of the xylose residues. And it revealed that the extractable hemicelluloses retained original structure without cleaving chemical linkages. Furthermore, a small amount of other minor hemicelluloses (β-glucans) including xylans in the extractable hemicelluloses could be identified by NMR and other approaches. Keywords: Hemicellulose of Quercus Linn wood, Steam explosion, Biodegradation of Lentinus edodes, TGA/DTG, FT-IR, NMR, HSQC

Tunnel lining defects are one of the most common problems that tunnels experience during operation, and they can pose severe safety risks. The most popular nondestructive testing method for detecting tunnel lining defects is ground penetrating radar (GPR), one of the basic geophysical applications. However, detection responses might differ significantly from the real shape of tunnel lining defects, making it challenging to identify and interpret. When data quality is poor, interpretation and identification become more challenging, resulting in a high cost of tunnel repairs. The improved back projection (BP) imaging and robust principal component analysis (RPCA) are used in this work to offer a GPR data processing method. Even in the event of poor data quality, our method could recover GPR responses, allowing the shapes and locations of tunnel lining flaws to be clearly depicted. With BP imaging, this approach recovers the tunnel defects’ responses to better forms and positions, and with RPCA, it further isolates the target imaging from clutters. Several synthetic data demonstrate that the approach presented in this work may successfully repair and extract the positions and forms of lining defects, making them easier to identify and comprehend. Furthermore, our technique was used to GPR data gathered from the Qiyue Mountain Tunnel in China, yielding more accurate findings than the traditional method, which was validated by the actual scenario to illustrate the efficiency of our method on real data.

Rare Earth Upconversion nanoparticles (UCNPs) are a type of material that emits high-energy photons by absorbing two or more low-energy photons caused by the anti-stokes process. It can emit ultraviolet (UV) visible light or near-infrared (NIR) luminescence upon NIR light excitation. Due to its excellent physical and chemical properties, including exceptional optical stability, narrow emission band, enormous Anti-Stokes spectral shift, high light penetration in biological tissues, long luminescent lifetime, and a high signal-to-noise ratio, it shows a prodigious application potential for bio-imaging and photodynamic therapy. This paper will briefly introduce the physical mechanism of upconversion luminescence (UCL) and focus on their research progress and achievements in bio-imaging, bio-detection, and photodynamic therapy.

Abstract The chemobiomechanical signatures of diseased cells are often distinctively different from that of healthy cells. This mainly arises from cellular structural/compositional alterations induced by disease development or therapeutic molecules. Therapeutic shock waves have the potential to mechanically destroy diseased cells and/or increase cell membrane permeability for drug delivery. However, the biomolecular mechanisms by which shock waves interact with diseased and healthy cellular components remain largely unknown. By integrating atomistic simulations with a novel multiscale numerical framework, this work provides new biomolecular mechanistic perspectives through which many mechanosensitive cellular processes could be quantitatively characterised. Here we examine the biomechanical responses of the chosen representative membrane complexes under rapid mechanical loadings pertinent to therapeutic shock wave conditions. We find that their rupture characteristics do not exhibit significant sensitivity to the applied strain rates. Furthermore, we show that the embedded rigid inclusions markedly facilitate stretch-induced membrane disruptions while mechanically stiffening the associated complexes under the applied membrane stretches. Our results suggest that the presence of rigid molecules in cellular membranes could serve as “mechanical catalysts” to promote the mechanical destructions of the associated complexes, which, in concert with other biochemical/medical considerations, should provide beneficial information for future biomechanical-mediated therapeutics.

Abstract Background To evaluate the macular sensitivity changes after half-dose photodynamic therapy (PDT) for chronic central serous chorioretinopathy (CSCR). Methods Eighteen patients (26 eyes) with chronic CSCR were recruited in the same hospital between April 2011 and December 2012. All patients were treated with one session of half-dose PDT after complete ophthalmic examination. Macular sensitivity examination was performed at baseline and 1, 3 and 6 months post-treatment. Mean sensitivity (MS) of the central 10 degrees (10°) and 4 degrees (4°), mean deviation (MD) and pattern standard deviation (PSD) on automated static perimetry (Humphrey Field Analyzer II-750) were used for analysis. Results There was significant improvement of the 10°MS from baseline (29.76 ± 1.51 dB) to 1 month (31.74 ± 1.56 dB), 3 months (31.51 ± 1.38 dB) and 6 months (31.19 ± 1.61 dB) after treatment (P

Albiflorin (AF) is a small molecule (MW 481) isolated from Paeoniae radix, a plant used as a remedy for various conditions with pathogenesis shared by metabolic diseases. Reported here is our characterization of its therapeutic profiles in three mouse models with distinctive pathological features of metabolic syndrome (MetS). Our results firstly showed that AF alleviated high fat (HF) induced obesity and associated glucose intolerance, suggesting its therapeutic efficacy for MetS. In the type 2 diabetes (T2D) model induced by a combination of HF and low doses of streptozotocin, AF lowered hyperglycaemia and improved insulin-stimulated glucose disposal. In the non-alcoholic steatohepatitis-like model resulting from a HF and high cholesterol (HF-HC) diet, AF reversed the increased liver triglyceride and cholesterol, plasma aspartate aminotransferase, and liver TNFα mRNA levels. Consistent with its effect in promoting glucose disposal in HF-fed mice, AF stimulated glucose uptake and GLUT4 translocation to the plasma membrane in L6 myotubes. However, these effects were unlikely to be associated with activation of insulin, AMPK, ER, or cellular stress signalling cascades. Further studies revealed that AF increased the whole-body energy expenditure and physical activity. Taken together, our findings indicate that AF exerts a therapeutic potential for MetS and related diseases possibly by promoting physical activity associated whole-body energy expenditure and glucose uptake in muscle. These effects are possibly mediated by a new mechanism distinct from other therapeutics derived from Chinese medicine.

The present study investigated the effects of matrine on non-alcoholic steatohepatitis (NASH) in mice induced by a methionine choline-deficient (MCD) diet and the mechanism involved. The study was performed in C57B/6J mice fed a MCD diet for 6 weeks to induce NASH with or without the treatment of matrine (100 mg/kg/day in diet). Metformin was used (250 mg/kg/day in diet) as a comparator for mechanistic investigation. Administration of matrine significantly reduced MCD-induced elevations in plasma ALT and AST but without changing body or liver fat content. Along with alleviating liver injury, matrine suppressed MCD-induced hepatic inflammation (indicated by TNFα, CD68, MCP-1, and NLRP3) and fibrosis (indicated by collagen 1, TGFβ, Smad3, and sirius-red staining). In comparison, metformin treatment did not show any clear sign of effects on these parameters indicative of NASH. Further examination of the liver showed that matrine treatment rescued the suppressed HSP72 (a chaperon protein against cytotoxicity) and blocked the induction of mTOR (a key protein in a stress pathway). In keeping with the lack of the improvement of the NASH features, metformin did not show any significant effect against MCD-induced changes in HSP72 and mTOR. Matrine protects against MCD-induced development of NASH which is refractory to metformin treatment. Its anti-NASH effects involve enhancing HSP72 and downregulating mTOR but do not rely on amelioration of hepatosteatosis.

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease that can progress from simple hepatic steatosis to nonalcoholic steatohepatitis (NASH), and even further to liver cirrhosis or liver cancer. Overconsumption of high fat and/or carbohydrate are among the most common lifestyle factors that drive the development and progression of NAFLD. This review evaluates recent reports on the involvement of autophagy and endoplasmic reticulum (ER) stress in the pathogenesis of NAFLD. Here, we reveal a mechanism of an intrinsically linked axis of impaired autophagy and unresolved ER stress that mediates the development and progression of NAFLD resulting from the overconsumption of high fat and/or carbohydrate.

Black cumin (Nigella sativa) seed extract has been shown to improve dermatological conditions, yet its beneficial effects for skin are not fully elucidated. Herein, Thymocid®, a chemically standardized black cumin seed extract, was investigated for its cosmeceutical potential including anti-aging properties associated with modulation of glycation, collagen cross-linking, and collagenase and elastase activities, as well as antimelanogenic effect in murine melanoma B16F10 cells. Thymocid® (50, 100, and 300 µg/mL) inhibited the formation of advanced glycation end-products (by 16.7–70.7%), collagen cross-linking (by 45.1–93.3%), collagenase activity (by 10.4–92.4%), and elastases activities (type I and III by 25.3–75.4% and 36.0–91.1%, respectively). In addition, Thymocid® (2.5–20 µg/mL) decreased melanin content in B16F10 cells by 42.5–61.6% and reduced cellular tyrosinase activity by 20.9% (at 20 µg/mL). Furthermore, Thymocid® (20 µg/mL for 72 h) markedly suppressed the mRNA expression levels of melanogenesis-related genes including microphthalmia-associated transcription factor (MITF), tyrosinase-related protein 1 (TYRP1), and TYRP2 to 78.9%, 0.3%, and 0.2%, respectively. Thymocid® (10 µg/mL) also suppressed the protein expression levels of MITF (by 15.2%) and TYRP1 (by 97.7%). Findings from this study support the anti-aging and antimelanogenic potential of Thymocid® as a bioactive cosmeceutical ingredient for skin care products.

Background: Piperine is the primary pungent alkaloid isolated from the fruit of black peppercorns. Piperine is used frequently in dietary supplements and traditional medicines. The objective of the present study was to investigate the effects of piperine on the testis development in the pubertal rat.Methods: Piperine (0 or 5 or 10 mg/kg) was gavaged to 35-day-old male Sprague-Dawley rats for 30 days. Serum levels of testosterone (T), luteinizing hormone (LH), and follicle-stimulating hormone (FSH) were measured. The development of adult Leydig cell population was also analyzed 65 days postpartum. For in vitro studies, immature Leydig cells were isolated from 35-day-old male rats and treated with 50 μM piperine in the presence of different steroidogenic stimulators/substrates for 24 h.Results: Thirty-day treatment of rats with piperine significantly increased serum T levels without affecting LH concentrations. However, piperine treatment reduced serum FSH levels. Consistent with increase in serum T, piperine increased Leydig cell number, cell size, and multiple steroidogenic pathway proteins, including steroidogenic acute regulatory protein, cholesterol side-chain cleavage enzyme, 3β-hydroxysteroid dehydrogenase 1, 17α-hydroxylase/20-lyase, and steroidogenic factor 1 expression levels. Piperine significantly increased the ratio of phospho-AKT1 (pAKT1)/AKT1, phosphos-AKT2 (pAKT2)/AKT2, and phospho-ERK1/2 (pERK1/2)/ERK1/2 in the testis. Interestingly, piperine inhibited spermatogenesis. Piperine in vitro also increased androgen production and stimulated cholesterol side-chain cleavage enzyme and 17α-hydroxylase/20-lyase activities in immature Leydig cells.Conclusion: Piperine stimulates pubertal Leydig cell development by increasing Leydig cell number and promoting its maturation while it inhibits spermatogenesis in the rat. ERK1/2 and AKT pathways may involve in the piperine-mediated stimulation of Leydig cell development.

Diabetic retinopathy is the leading cause of blindness in working age individuals in developed countries. However, the role of inflammation in the pathogenesis of DR is not completely understood. This is an observational clinical research enrolling 80 type II diabetic patients who had undergone cataract surgeries either with DR or without DR. All cases were further categorized by the proliferative stages of retinal neovascularization and by the lengths of diabetic history. The levels of inflammatory cytokines including IL-1β, IL-6, IL-8, IL-17, and TNF-α in aqueous humour were tested. Results in this study indicated that these cytokine levels were increased in DR patients and might have a synergistic effect on the pathogenesis of this disease. They were also elevated along with the progression of neovascularization, reflecting the severity of DR. The results also suggested that for diabetic patients, the higher these levels are, the sooner retinal complications might appear. In conclusion, the levels of inflammatory cytokines IL-1β, IL-6, IL-8, IL-17A, and TNF-α in aqueous humour may be associated with the pathogenesis, severity, and prognosis of DR.

Five terpenoids (1–5) from a vegetable plant Acanthopanax trifoliatus (L.) Merr. were investigated for their effects on human prostate cancer cells. The diterpenoid (3) and triterpenoids (4 and 5) were found to inhibit the growth and stimulate apoptosis in PC-3 cells. The effects of these terpenoids on PC-3 cells were associated with strong suppression of nuclear factor-κB (NF-κB) and signal transducer and activator of transcription 3 (STAT3). These terpenoids also inhibited the expression of survivin, a downstream target of NF-κB and STAT3. The in vivo study using a xenograft mouse model showed that 5 strongly inhibited the formation and growth of PC-3 tumours. Moreover, treatment with 5 strongly decreased the expression of phospho-STAT3 and survivin in PC-3 tumours. Our results indicate that 5 has preventive efficacy on the development of PC-3 xenograft tumours. This terpenoid may serve as a candidate for future development as a novel agent for prostate cancer prevention.

Misfolded and aberrant proteins have been found to be associated with myocardial cell injury. Thus, increased clearance of misfolded or aggregated proteins via autophagy might be a potential option in preventing myocardial cell injury. Sevoflurane may ameliorate myocardial cell injury by affecting sirtuin 1- (SIRT1-) mediated autophagy. Rat models with myocardial cell injury were induced by limb ischemia reperfusion. The model rats received different treatments: sevoflurane, nicotinamide, and autophagy inhibitor 3-methyladenine (3-MA). Autophagy was observed by SEM. The levels of SIRT1 and microtubule-associated protein 1A/1B-light chain 3 (LC3) were measured. Present findings demonstrated that limb ischemia reperfusion induced autophagy. Sevoflurane increased the level of SIRT1, which deacetylated LC3 and further increased autophagic rates. On the other hand, the autophagy was inhibited by sevoflurane and or the inhibitors of SIRT1 and LC3. Present results demonstrated a novel molecular mechanism by which sevoflurane induced autophagy by increasing the level of SIRT1 and reducing the acetylation of LC3.

Objective: To compare the performance of a new tuberculosis-related interferon gamma release assay (TB-IGRA) with that of QuantiFERON-TB Gold In-Tube (QFT-GIT) for TB infection diagnosis in China. Materials and Methods: A total of 458 active TB patients and 378 healthy individuals were enrolled. Among the 458 active TB patients, 395 had pulmonary TB and 63 had extra-pulmonary TB. The blood samples were collected from the active TB patients and health controls; then TB-IGRA and QFT-GIT were used to detect interferon gamma (IFN-γ) levels. Results: The sensitivity, specificity, positive predictive value, and negative predictive value in TB infection diagnosis for active TB by the TB-IGRA were 83.4%, 94.2%, 94.5%, and 82.4%, respectively. For QFT-GIT, the sensitivity, specificity, positive predictive value, and negative predictive value in TB infection diagnosis for active TB were 81.4%, 97.1%, 97.1%, and 81.2%, respectively. Conclusions: TB-IGRA had a high sensitivity and specificity for TB infection; it could be comparable with the QFT-GIT assay. It might be a powerful assisting tool for TB infection diagnosis in the Chinese clinical setting.

We constructed dynamic Ebola virus disease (EVD) transmission models to predict epidemic trends and evaluate intervention measure efficacy following the 2014 EVD epidemic in West Africa. We estimated the effective vaccination rate for the population, with basic reproduction number (R0) as the intermediate variable. Periodic EVD fluctuation was analyzed by solving a Jacobian matrix of differential equations based on a SIR (susceptible, infective, and removed) model. A comprehensive compartment model was constructed to fit and predict EVD transmission patterns, and to evaluate the effects of control and prevention measures. Effective EVD vaccination rates were estimated to be 42% (31-50%), 45% (42-48%), and 51% (44-56%) among susceptible individuals in Guinea, Liberia and Sierra Leone, respectively. In the absence of control measures, there would be rapid mortality in these three countries, and an EVD epidemic would be likely recur in 2035, and then again 8~9 years later. Oscillation intervals would shorten and outbreak severity would decrease until the periodicity reached ~5.3 years. Measures that reduced the spread of EVD included: early diagnosis, treatment in isolation, isolating/monitoring close contacts, timely corpse removal, post-recovery condom use, and preventing or quarantining imported cases. EVD may re-emerge within two decades without control and prevention measures. Mass vaccination campaigns and control and prevention measures should be instituted to prevent future EVD epidemics.

Five new oxygenated pimarane diterpenes, named scopararanes C–G (1–5) were isolated from the culture of a marine sediment-derived fungus Eutypella scoparia FS26 obtained from the South China Sea. The structures of these compounds were established on the basis of extensive spectroscopic analysis. The absolute configurations of compounds 1–5, were determined by CD spectroscopic analysis and comparison with literature data. All isolated compounds (1–5) were evaluated for their cytotoxic activities against MCF-7, NCI-H460, and SF-268 tumor cell lines by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) method.

α-Tomatine is a glycoalkaloid found in tomatoes and curcumin is a major yellow pigment of turmeric. In the present study, the combined effect of these two compounds on prostate cancer cells was studied. Treatment of different prostate cancer cells with curcumin or α-tomatine alone resulted in growth inhibition and apoptosis in a concentration-dependent manner. Combinations of α-tomatine and curcumin synergistically inhibited the growth and induced apoptosis in prostate cancer PC-3 cells. Effects of the α-tomatine and curcumin combination were associated with synergistic inhibition of NF-κB activity and a potent decrease in the expression of its downstream gene Bcl-2 in the cells. Moreover, strong decreases in the levels of phospho-Akt and phosphor-ERK1/2 were found in PC-3 cells treated with α-tomatine and curcumin in combination. In animal experiment, SCID mice with PC-3 xenograft tumors were treated with α-tomatine and curcumin. Combination of α-tomatine and curcumin more potently inhibited the growth of PC-3 tumors than either agent alone. Results from the present study indicate that α-tomatine in combination with curcumin may be an effective strategy for inhibiting the growth of prostate cancer.

Frequencies of up to 3% of beak deformity (normally a crossed beak) occur in some indigenous chickens in China, such as and Beijing-You. Chickens with deformed beaks have reduced feed intake, growth rate, and abnormal behaviors. Beak deformity represents an economic as well as an animal welfare problem in the poultry industry. Because the genetic basis of beak deformity remains incompletely understood, the present study sought to identify important genes and metabolic pathways involved in this phenotype. Digital gene expression analysis was performed on deformed and normal beaks collected from Beijing-You chickens to detect global gene expression differences. A total of >11 million cDNA tags were sequenced, and 5,864,499 and 5,648,877 clean tags were obtained in the libraries of deformed and normal beaks, respectively. In total, 1,156 differentially expressed genes (DEG) were identified in the deformed beak with 409 being up-regulated and 747 down-regulated in the deformed beaks. qRT-PCR using eight genes was performed to verify the results of DGE profiling. Gene ontology (GO) analysis highlighted that genes of the keratin family on GGA25 were abundant among the DEGs. Pathway analysis showed that many DEGs were linked to the biosynthesis of unsaturated fatty acids and glycerolipid metabolism. Combining the analyses, 11 genes (MUC, LOC426217, BMP4, ACAA1, LPL, ALDH7A1, GLA, RETSAT, SDR16C5, WWOX, and MOGAT1) were highlighted as potential candidate genes for beak deformity in chickens. Some of these genes have been identified previously, while others have unknown function with respect to thus phenotype. To the best of our knowledge, this is the first genome-wide study to investigate the transcriptome differences in the deformed and normal beaks of chickens. The DEGs identified here are worthy of further functional characterization.

Celecoxib is a specific cyclooxygenase-2 inhibitor with poor solubility and low bioavailability. A solid selfmicroemulsifying drug delivery system of celecoxib was therefore developed to improve in vitro drug solubility and in vivo absorption. Solubility testing, compatibility testing and pseudo-ternary phase diagrams were employed in the design. Morphological observation, droplet size and in vitro release were used to characterize the formulation. The optimized celecoxib-liquid self-microemulsifying drug delivery system was determined as 10 % of celecoxib, 25 % of medium chain triglycerides, 56.25 % of emulsifier and 18.75 % of Transcutol HP. 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide assay was used to investigate the cytoxicity of active pharmaceutical ingredients, blank self-microemulsion and celecoxib liquid self-microemulsifying drug delivery system on Caco-2 cells. Celecoxib solid self-microemulsifying drug delivery system was prepared with Neusilin-US2 as a solid adsorbent and characterized using scanning electron microscopy, X-ray, Fourier-transform infrared spectroscopy, differential scanning calorimetry and in vitro release. Celecoxib liquid self-microemulsifying drug delivery system had a clear and transparent light-yellow appearance with average particle size of about 22.68 nm, zeta potential of -31.92 mv, and polydisperse coefficient of 0.141. 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide results showed that the formulations virtually had no cytotoxic effect on the cells. The results also showed that celecoxib existed in an amorphous state in celecoxib-solid self-microemulsifying drug delivery system, and the celecoxib-liquid self-microemulsifying drug delivery system and celecoxib-solid-self-microemulsifying drug delivery system had a dissolution degree of more than 90 % in different media with good stability. The pharmacokinetic studies showed that the area under curve of the liquid self-microemulsifying drug delivery system and self-microemulsifying drug delivery system increased by 6.59 and 6.37 folds, respectively, compared with celecoxib suspension. The findings showed that the developed solid self-microemulsion formulations improved the bioavailability of the drug with no cytotoxicity, hence the formulation can serve as a promising carrier for the oral delivery of celecoxib. [ABSTRACT FROM AUTHOR]

Subretinal fibrosis (SF) is an important cause of submacular neovascularization that leads to permanent vision loss, but has no effective clinical treatment. The present study examined the influence of metformin on SF, and investigated whether the mechanism involves the microRNA (miR)-140-3p/LIN28B/JNK/STAT3-mediated regulation of oxidative stress, angiogenesis and fibrosis-associated indicators. A mouse model of laser-induced SF was established. In addition, an ARPE-19 fibrotic cell model was established using TGF-β1. A Cell Counting Kit-8 assay was used to examine cell viability. Flow cytometry was used to measure reactive oxygen species levels, and western blotting was used to detect the levels of proteins associated with epithelial-mesenchymal transition (EMT), signaling and fibrosis. The levels of superoxide dismutase, malondialdehyde, glutathione-peroxidase and catalase were measured using kits. Scratch assays and Transwell assays were used to assess cell migration and invasion, respectively, and reverse transcription-quantitative PCR was used to determine the levels of miR-140-3p and LIN28B. Dual-luciferase assays were used to verify the targeting relationship between miR-140-3p and LIN28B, and coimmunoprecipitation was used to confirm the interaction between LIN28B and JNK. Masson staining and hematoxylin and eosin staining were used to examine collagenous fibers and the histopathology of eye tissue. In ARPE-19 cells induced by TGF-β1, metformin promoted miR-140-3p expression and inhibited LIN28B expression and JNK/STAT3 pathway activation, thereby inhibiting oxidative stress, EMT and fibrosis in ARPE-19 cells. The overexpression of LIN28B or treatment with the JNK/STAT3 agonist anisomycin partially reversed the inhibitory effect of metformin on oxidative stress and fibrosis in ARPE-19 cells. The dual-luciferase reporter assay and coimmunoprecipitation assay showed that miR-140-3p targeted the 3' untranslated region of LIN28B mRNA and inhibited LIN28B expression. LIN28B targeted and bound to JNK and regulated the JNK/STAT3 pathway. Therefore, it may be concluded that metformin can promote miR-140-3p expression, inhibit LIN28B and then inhibit the JNK/STAT3 pathway to alleviate SF. [ABSTRACT FROM AUTHOR]

Inborn errors of the signal transducer and activator of transcription 1 (STAT1) result in four types of immunodeficiency disease with varying degrees of impaired STAT1 function: autosomal recessive (AR) complete STAT1 deficiency, AR partial STAT1 deficiency, autosomal dominant (AD) STAT1 deficiency, and AD STAT1 gain-of-function (STAT1-GOF). Of which, the STAT1-GOF mutations promote a clinical syndrome of immune dysregulation characterized by recurrent infections, especially chronic mucocutaneous candidiasis (CMC) and Talaromyces marneffei infection and predisposition to humoral autoimmunity. STAT1-GOF mutations lead to enhanced phosphorylation of STAT1 (pSTAT1), delayed dephosphorylation, and impaired nuclear dephosphorylation. As a result, the development of T helper (Th) 17 cells is impaired, limiting the production of interleukin (IL)-17, which plays an important role in antifungal immunity. Additionally, mutations can also cause a decrease in the proportion of CD4+, CD8+, and natural killer (NK) cells. Recent research demonstrated that in the absence of overt infection, STAT-GOF mice can disrupt naïve CD4+ T cell homeostasis and promote expansion and differentiation of abnormal T-follicular helper/T-helper 1-like (Tfh/Th1-like) T cells and germinal center-like (GC-like) B cells, and thus reminds us of the complex molecular mechanism of autoimmune disease with/without fungal infection, which may further involve specific clinical treatment including antifungal and anti-autoimmunity therapies. In addition, sex and location of mutation were also associated with the clinical phenotype. Individuals with DNA binding domain (DBD) mutations had a higher prevalence of autoimmunity and aberrant B cell activation. Disrupted CD4+ T cell homeostasis occurred sooner and more robustly in females, highlighting the importance of specific treatment to normalize STAT1 expression and restore immune tolerance in patients with STAT1-GOF syndrome. Herein, we provide a comprehensive review of STAT1-GOF aiming to further clarify the regulatory mechanism of cellular and humoral immune deficiency in patients with fungal infection with or without autoimmunity.