Application of a new multi-element integrated teaching mode based on bite-sized teaching, flipped classroom, and MOOC in clinical teaching of obstetrics and gynaecology.

CONTEXT: Effective clinical medical student education includes attention to teaching approaches. This study assessed the impact of a new multi-element teaching mode that utilizes Bite-Sized Teaching, flipped classroom, and MOOC on learner perception in an Obstetrics and gynaecology clerkship. METHODS: A Two-stage crossover design study was conducted of a multi-element teaching mode compared to traditional teaching mode in an academic year. Participants included Ninety-six medical students practicing obstetrics and gynecology in our hospital, randomly divided into two groups respectively underwent multi-element teaching mode and traditional teaching mode. After each semester, a final test (including theoretical and clinical practical test) was conducted.When an academic year was completed, post intervention survey assessed learner perceptions of the intervention. RESULT: In order to comprehensively test students' performance after study, we take theoretical and practical examinations. The theoretical examination mainly tests students' grasp of basic knowledge points, while the practical examination focuses on the examination of students' diagnosis and treatment of diseases. There were statistically significant differences both in the theoretical and clinical practical scores between the new multi-element integrated teaching mode and the traditional teaching mode, specifically as follows: In the end of first semester, the theoretical scores of the two groups were respective 43.75 ± 3.42 vs. 42.07 ± 2.90, and clinic practical test scores were respective 44.93 ± 2.42 vs. 43.37 ± 2.52; In the end of second semester, the theoretical scores of the two groups were respective 44.30 ± 2.69 vs. 42.25 ± 3.39, and clinic practical test scores were respective 43.79 ± 2.25 vs. 41.93 ± 2.80.(p < 0.05). The results of questionnaires demonstrated that 80.21% of the students showed preference for the new multi-element integrated teaching mode comparing to traditional teaching methods. CONCLUSION: The new multi-element integrated teaching mode is well accepted by the students and can improve the students' mastery of knowledge, and can improve the students' clinical comprehensive ability. The new multi-element integrated teaching mode is shown more preference than traditional teaching mode in the teaching of Obstetrics and Gynaecology. Further long term study is needed carried out to consolidate our conclusion. The new multi-element integrated teaching mode may have positive effects on clinical teaching of Obstetrics and Gynaecology.

Analysis of the application effect of a rapid response team in emergency cesarean section.

INTRODUCTION: Emergency cesarean section is one of the most critical methods in the treatment of high-risk emergency obstetric cases. The aim of this study was to explore the clinical effect of constructing a Rapid Response Team (RRT) in emergency cesarean section. METHODS: This is a pre- and post-implementation study. The patients who underwent emergency cesarean section were retrospectively analyzed and divided into an experimental group and a control group. There were 52 patients (June-December 2020) in the control group who underwent routine emergency cesarean section without an RRT, and 51 patients (January-June 2021) in the experimental group who underwent emergency cesarean section with an RRT. The operation time indexes (DOI, decision-to-operating room interval; O-I, operating room-to-incision interval; DII, decision-to-incision interval; I-D, incision-to-delivery interval; DDI, decision-to-delivery interval), DDI pass rate, neonatal Apgar score and maternal complications in the two groups were compared. Moreover, the management time trends (DOI, DII, and DDI) in the experimental group were analyzed. RESULTS: The DDI, DII, DOI, and O-I of the experimental group were shorter than those of the control group, and the differences were significant (p < 0.05). The DDI pass rate in the experimental group was higher than that in the control group, and the difference was significant (p < 0.01). The 1-min Apgar score of the experimental group was higher than that of the control group (p < 0.05). The key intervals of emergency cesarean section in the experimental group leveled off after approximately 3 to 4 months. CONCLUSION: In the face of emergency situations, the implementation of an emergency cesarean section RRT can improve delivery intervals for emergency cesarean and would be conducive to maternal and infant safety.

A novel clinical prediction model of severity based on red cell distribution width, neutrophil-lymphocyte ratio and intra-abdominal pressure in acute pancreatitis in pregnancy.

BACKGROUND: Acute pancreatitis in pregnancy (APIP) with a high risk of death is extremely harmful to mother and fetus. There are few models specifically designed to assess the severity of APIP. Our study aimed to establish a clinical model for early prediction of severity of APIP. METHODS: A retrospective study in a total of 188 patients with APIP was enrolled. The hematological indicators, IAP (intra-abdominal pressure) and clinical data were obtained for statistical analysis and prediction model construction. RESULTS: According to univariate and multivariate logistic regression analysis, we found that red cell distribution width (RDW), neutrophil-lymphocyte ratio (NLR) and Intra-abdominal pressure (IAP) are prediction indexes of the severity in APIP (p-value < 0.05). Our novel clinical prediction model was created by based on the above three risk factors and showed superior predictive power in primary cohort (AUC = 0.895) and validation cohort (AUC = 0.863). A nomogram for severe acute pancreatitis in pregnancy (SAPIP) was created based on the three indicators. The nomogram was well-calibrated. CONCLUSION: RDW, NLR and IAP were the independent risk factors of APIP. Our clinical prediction model of severity in APIP based on RDW, NLR and IAP with predictive evaluation is accurate and effective.

MicroRNAs: key regulators of the trophoblast function in pregnancy disorders.

The placenta is essential for a successful pregnancy and healthy intrauterine development in mammals. During human pregnancy, the growth and development of the placenta are inseparable from the rapid proliferation, invasion, and migration of trophoblast cells. Previous reports have shown that the occurrence of many pregnancy disorders may be closely related to the dysfunction of trophoblasts. However, the function regulation of human trophoblast cells in the placenta is poorly understood. Therefore, studying the factors that regulate the function of trophoblast cells is necessary. MicroRNAs (miRNAs) are small, non-coding, single-stranded RNA molecules. Increasing evidence suggests that miRNAs play a crucial role in regulating trophoblast functions. This review outlines the role of miRNAs in regulating the function of trophoblast cells and several common signaling pathways related to miRNA regulation in pregnancy disorders.

Efficacy of Pgp3 vaccination for Chlamydia urogenital tract infection depends on its native conformation.

Urogenital tract infections with Chlamydia trachomatis have frequently been detected among patients diagnosed with sexually transmitted infections, and such infections lead to inflammatory complications. Currently, no licensed chlamydial vaccine is available in clinical practice. We previously reported that immunization with recombinant C. trachomatis plasmid-encoded virulence factor Pgp3 provided cross-serovar protection against C. muridarum genital tract infection. Because Pgp3 is a homotrimer and human antisera only recognize the trimeric form of Pgp3, we compared the effects of the native conformation of Pgp3 (trimer) and heat-denatured Pgp3 (monomer) to determine whether the native conformation is dispensable for the induction of protective immunity against chlamydial vaginal challenge. Both Pgp3 trimer and monomer immunization induced corresponding specific antibody production, but only trimer-induced antibody recognized endogenous Pgp3, and trimer-immunized mouse splenocytes showed the highest IFN-γ production upon restimulation with the chlamydial elementary body or native Pgp3 in vitro. Importantly, only Pgp3 trimer-immunized mice showed shortened lower genital tract chlamydial shedding and decreased upper genital tract pathology. Thus, Pgp3-induced protective immunity against Chlamydia urogenital tract infection is highly dependent on the native conformation, which will guide the design of Pgp3-based polypeptides and multi-subunit chlamydial vaccines.

Application of online teaching mode combining case studies and the MOOC platform in obstetrics and gynecology probation teaching.

OBJECTIVE: To explore the application effect of the clinical basic integration teaching mode constructed by case studies and the MOOC platform in obstetrics and gynecology internship teaching in the face of public health emergencies. METHODS: One hundred ten clinical medical students of grade 2020 were selected as the experimental group, and 110 clinical medical students of grade 2021 were selected as the control group. The experimental group adopted the online teaching mode combined with case studies and the MOOC platform, while the control group adopted the offline traditional probation teaching method. Comprehensive test and questionnaire were used to evaluate and compare the teaching effect of the two groups of students. RESULTS: The experimental group was found to be superior to the control group in the quality assessment of complete medical record writing and the ability assessment of diagnosis and analysis of typical obstetrics and gynecology cases (P < 0. 05). However, the score of professional knowledge was lower than that of the control group (P < 0. 05). The results of questionnaire survey showed that the satisfaction of the experimental group in stimulating learning interest, enhancing problem solving ability, enhancing communication and clinical thinking ability, enhancing team cooperation awareness and independent innovation ability was higher than that of the control group (P < 0.01). The satisfaction of teacher-student interaction was also better (P < 0.05). However, in terms of strengthening theoretical understanding, the satisfaction of the experimental group was lower than that of the control group, but with no significant difference (P > 0.05). CONCLUSION: During the epidemic period, we designed a new online teaching mode, which can be applied to the probation teaching of obstetrics and gynecology. In our study, compared with traditional offline teaching, the new online teaching mode could improve students' ability of case writing and case analysis. However, more teaching practice is needed to complete this online teaching mode.

The role of an enzymatically inactive CPAF mutant vaccination in Chlamydia muridarum genital tract infection.

Chlamydia trachomatis urogenital tract infection causes pelvic inflammatory disease and infertility, increases the risk of co-infection with HPV and HIV. Chlamydial vaccination is considered the most promising approach to prevent and control its infection. Among various chlamydial vaccine candidates, chlamydial protease-like activity factor (CPAF) have been reported to provide robust protective immunity against genital chlamydial infection in mice with reduced vaginal shedding and oviduct pathology. However, CPAF is a serine protease which has enzymatical activity to degrade a large number of substrates. In order to increase the safety of CPAF vaccine, in this study, we used a mutant CPAF that is deficient in enzymatical activity to determine whether proteolytic activity of CPAF affect its vaccine efficacy. The wild type or mutant CPAF immunization causes a significant lower chlamydial shedding from the vaginal and resolve the infection as early as day 20, compared to day 28 in adjuvant control mice. More important, reduced upper reproductive tract pathology were also observed in these two groups. The mutant or wild type CPAF immunization induced not only robust splenic IFN-γ and serum IgG2a but also sIgA secretion in the vaginal fluids. Furthermore, neutralization of chlamydia with immune sera did not provide protection against oviduct pathology. However, adoptive transfer of CD4+ splenocytes isolated from the mutant or wild type CPAF immunized mice resulted in a significant and comparable reduced oviduct pathology. Our results indicate mutant CPAF vaccination is as same efficacy as wild type, and the protection relies on CD4+ T cells, which will further promote the development of CPAF as clinical chlamydial vaccine.

Tanshinone II A enhances pyroptosis and represses cell proliferation of HeLa cells by regulating miR-145/GSDMD signaling pathway.

Cervical cancer is the fourth most common cancer in women globally. Lack of effective pharmacotherapies for cervical cancer mainly attributed to an elusive understanding of the mechanism underlying its pathogenesis. Pyroptosis plays a key role in inflammation and cancer. Our study identified microRNA (miR) 145 (miR-145)/gasdermin D (GSDMD) signaling pathway as critical mediators in the effect of tanshinone II A on HeLa cells. In the present study, we found that treatment of tanshinone II A led to an obvious repression of cell proliferation and an increase in apoptosis on HeLa cells, especially in high concentration. Compared with the controlled group, tanshinone II A enhanced the activity of caspase3 and caspase9. Notably, the results demonstrated that tanshinone II A regulated cell proliferation of HeLa cells by regulating miR-145/GSDMD signaling pathway. Treatment of tanshinone II A significantly up-regulated the expression of GSDMD and miR-145. After transfection of si-miR-145 plasmids, the effects of tanshinone II A on HeLa cells were converted, including cell proliferation, apoptosis and pyroptosis. In addition, the results showed that tanshinone II A treatment altered the expression level of PI3K, p-Akt, NF-kB p65 and Lc3-I. Collectively, our findings demonstrate that tanshinone II A exerts anticancer activity on HeLa cells by regulating miR-145/GSDMD signaling. The present study is the first time to identify miR-145 as a candidate target in cervical cancer and show an association between miR-145 and pyroptosis, which provides a novel therapy for the treatment of cervical cancer.

CircZDHHC20 represses the proliferation, migration and invasion in trophoblast cells by miR-144/GRHL2 axis.

BACKGROUND: Preeclampsia (PE) is a prevalent pregnancy disorder that has been one of the leading causes of maternal and perinatal mortality worldwide. Circular RNAs (circRNAs) have recently considered as important regulators in PE pathogenesis. In the current study, we aimed to explore the impact and mechanisms of circRNA zinc finger DHHC-type palmitoyltransferase 20 (circZDHHC20) in PE pathogenesis. METHODS: RNase R assay and reverse transcription with Oligo(dT)18 primers were performed to confirm that circZDHHC20 was indeed circular transcript. The expression of circZDHHC20, grainyhead-like 2 (GRHL2) and miR-144 were assessed by quantitative real-time polymerase chain reaction (qRT-PCR). Subcellular localization assay was used to determine whether circZDHHC20 was predominantly present in the cytoplasm. The target correlations between miR-144 and circZDHHC20 or GRHL2 were confirmed using dual-luciferase reporter and RNA immunoprecipitation (RIP) assays. Cell proliferation, migration, and invasion were detected by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetr-azolium (MTS), wound healing and transwell assays, respectively. Western blot was used for the quantification of GRHL2 protein level. RESULTS: Our data indicated that circZDHHC20 was up-regulated and miR-144 was down-regulated in PE placenta. CircZDHHC20 sequestered miR-144 by acting as a miR-144 sponge. CircZDHHC20 overexpression repressed trophoblast cell proliferation, migration, and invasion, while its knockdown exerted opposite effects. Moreover, miR-144 mediated the regulation of circZDHHC20 on trophoblast cell behaviors. GRHL2 was directly targeted and inhibited by miR-144. MiR-144 exerted regulatory effects on trophoblast cell proliferation, migration and invasion by GRHL2. Furthermore, circZDHHC20 modulated GRHL2 expression through sponging miR-144. CONCLUSION: Our study suggested that a high level of circZDHHC20 inhibited the proliferation, migration, and invasion in trophoblast cells at least partially through sponging miR-144 and up-regulating GRHL2, providing a novel mechanism of PE pathogenesis.

A single-nucleotide polymorphism in lnc-LAMC2-1:1 interferes with its interaction with miR-128 to alter the expression of deleted in colorectal cancer and its effect on the survival rate of subjects with ovarian cancer.

This study aimed to identify the association between lnc-LAMC2-1:1 polymorphism rs2147578 and the recurrence of ovary cancer, as well as to study the underlying mechanism of rs2147578 in ovary cancer. Real-time polymerase chain reaction, Western blot analysis, immunohistochemistry, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, Logrank test, and Kaplan-Meier analysis were carried out to explore the role of rs2147578 in ovary cancer. No obvious difference was observed concerning all clinical characteristics among 90 patients genotyped as CC (N = 28), CG (N = 38), and GG (N = 24) in their rs2147578 polymorphism. In addition, the subjects carrying the CC genotype had longer recurrence-free survival time and showed a lower level of malignancy compared with those carrying CG and GG genotypes. Lnc-LAMC2-1:1 and miR-128 were lowly expressed in the CC group, while deleted in colorectal cancer (DCC) was highly expressed in the CC group. Furthermore, DCC was identified as a target gene of miR-128, and miR-128 mimics decreased the luciferase activity of cells cotransfected with wild-type DCC 3'-untranslated region. Lnc-LAMC2:1-1 directly targeted and affected miR-128 expression, and the G allele in lnc-LAMC2-1:1 rs2147578 upregulated miR-128 expression. Transfection with a miR-128 precursor evidently downregulated the expression of lnc-LAMC2-1:1, miR-128, and DCC expression, but did not affect the expression of ABCC5 and body mass index. Finally, miR-128 precursor promoted cell proliferation and inhibited cell apoptosis. Compared with lnc-LAMC2-1:1 rs2147578C allele, the G allele increases the risk of ovarian cancer by reducing the binding between lnc-LAMC2-1:1 and miR-128-3p, which in turn further decreases the expression of DCC and inhibits cell apoptosis.

Hsa_circ_0107593 Suppresses the Progression of Cervical Cancer via Sponging hsa-miR-20a-5p/93-5p/106b-5p.

Circular RNAs (circRNAs) are a new class of single-stranded RNAs that form a continuous loop with crucial role in regulation of gene expression. Because their circular conformation conforms numerous properties, circRNAs have been investigated recently to demonstrate their important role in the development and progression of various cancers. However, the function of circRNAs and their regulatory outcomes in cervical cancer (CC) have rarely been explored. In this study, the role and molecular mechanism of hsa_circ_0107593 in cervical cancer are demonstrated. Quantitative polymerase chain reaction (qRT-PCR) was used to determine the expression of hsa_circ_0107593 and three miRNAs (hsa-miR-20a-5p, 93-5p, and 106b-5p) in paired CC tissues (tumor tissue vs. adjacent normal cervical tissue), CC cell lines, and human normal cervical epithelial immortalized cell line. A series of functional experiments were conducted to assess the function of hsa_circ_0107593 in CC development. The Receiver Operating Characteristic (ROC) curve was plotted to estimate the diagnostic value of hsa_circ_0107593 in CC. The dual-luciferase reporter assay was used to explore the interaction between hsa_circ_0107593 and hsa-miR-20a-5p/93-5p/106b-5p. Bioinformatic analysis was conducted to predict the target mRNAs, pathways, and functional enrichment. The results revealed that hsa_circ_0107593 has low expression in CC tissues and CC cell lines. Moreover, negative correlations of hsa_circ_0107593 expression were found against tumor diameter, FIGO stage, and myometrial invasion. Also, hsa_circ_0107593 impedes CC cell proliferation, migration, and invasion. Based on ROC curve analysis, hsa_circ_0107593 could serve as a diagnostic biomarker. Its low expression may indicate increased patient's risk to developing cervical cancer. Mechanistically, hsa_circ_0107593 serves as a sponge of hsa-miR-20a-5p, hsa-miR-93-5p, and hsa-miR-106b-5p. Collectively, our study implies that hsa_circ_0107593 has tumor-suppressing activity in CC by physically binding with hsa-miR-20a-5p, hsa-miR-93-5p, and hsa-miR-106b-5p.

Development of RGD-Functionalized PEG-PLA Micelles for Delivery of Curcumin.

Curcumin (Cur), a hydrophobic polyphenolic compound, possesses a wide range of biological activities. However, its prominent application in cancer treatment is limited due to low aqueous solubility and rapid metabolism. Recently, micelle-based drug delivery system has been proven to be an attractive alternative for poorly soluble drugs. In order to improve the application of Cur as an anti-cancer agent, in this study, we synthesized the αvß3 integrin-targeted peptide (RGD) functionalized polymer (RGD-PEG-PLA). The RGD conjugated Cur loaded micelles (Cur-RPP) were prepared using the thin-film hydration method with modification and the preparation process was optimized with a central composite design. The obtained Cur-RPP presented spherical shape with a particle size of 20 nm and high drug loading (4.70%). Compared with the Cur propylene glycol solution, the in vitro release of Cur from the prepared micelles showed the sustained-release property. Cellular uptake of Cur-RPP was found to be higher than that of non-RGD modified micelles due to the binding effect between αvß3 integrin and RGD in human umbilical vein endothelial cells (HUVEC) and mouse melanoma cell lines (B16). In B16 tumor-bearing mice, Cur-RPP showed the stronger inhibiting effect on growth of tumor compared with non-RGD modified micelles. It could be concluded from these results that the RGD modified micelles might be a potential carrier for Cur.

Polymorphism of avian leukosis virus subgroup E loci showing selective footprints in chicken.

Avian leukosis virus subgroup E (ALVE) is a family of endogenous retroviruses in the chicken genome. To investigate the genetic consequences of chicken domestication, we analyzed 18 ALVE loci in red jungle fowls, layers, broilers, and Chinese indigenous chickens. None of the ALVE loci tested were found in red jungle fowls, but 12 were present in domestic chickens. ALVE1 and ALVE16 are found in regions of the genome that harbor quantitative trait loci (QTL) affecting egg production traits. ALVE1 was fixed and ALVE16 was detected only in layers. By contrast, ALVE-b1, ALVE-b5, ALVE-b6, and ALVE-b8 integrated into regions of the genome that harbor QTL affecting meat production traits. Carrier frequencies of these four ALVE loci were high in broilers and low in Chinese local chickens; the loci were not found in the layers. This study demonstrated that insertionally polymorphic ALVE loci can illustrate the selective footprints in the chicken genome.

Development of a folate-modified curcumin loaded micelle delivery system for cancer targeting.

Targeted drug delivery system for tumor cells is an appealing platform on enhancing the therapeutic effects and reducing the side effects of the drug. In this study, we developed folate-modified curcumin (Cur) loaded micelles (Cur-FPPs) for cancer chemotherapy. The targeting material, Folate-PEG3000-PLA2000, was synthesized by the amide bond formation reaction. And the Cur loaded micelles were prepared by thin-film hydration method with mPEG2000-PLA2000 (Cur-PPs) or mPEG2000-PLA2000 and Folate-PEG3000-PLA2000 (Cur-FPPs) as carrier. A central composite design (CCD) was used to optimize the formulation, and the optimized Cur-FPPs was prepared with the weight ratio of Folate-PEG3000-PLA2000 and mPEG2000-PLA2000 at 1:9. The average size of the mixed micelles was 70nm, the encapsulating efficiency and drug-loading were 80.73±0.16% and 4.84±0.01%, respectively. Compared with the Cur propylene glycol solution, the in vitro release of Cur from Cur-FPPs showed a sustained manner. Furthermore, the in vitro cytotoxicity and cellular uptake of Cur-FPPs were significantly enhanced towards MCF-7 and HepG2 cells. The pharmacokinetic studies in rats indicated that a 3-fold increase in the half-life was achieved for Cur loaded micelle formulations relative to solubilized Cur. All the results demonstrated that folate-modified Cur micelles could serve as a potential nanocarrier to improve the solubility and anti-cancer activity of Cur.

Genome-wide association study of antibody response to Newcastle disease virus in chicken.

BACKGROUND: Since the first outbreak in Indonesia in 1926, Newcastle disease has become one of the most common and contagious bird diseases throughout the world. To date, enhancing host antibody response by vaccination remains the most efficient strategy to control outbreaks of Newcastle disease. Antibody response plays an important role in host resistance to Newcastle disease, and selection for antibody response can effectively improve disease resistance in chickens. However, the molecular basis of the variation in antibody response to Newcastle disease virus (NDV) is not clear. The aim of this study was to detect genes modulating antibody response to NDV by a genome-wide association study (GWAS) in chickens. RESULTS: To identify genes or chromosomal regions associated with antibody response to NDV after immunization, a GWAS was performed using 39,833 SNP markers in a chicken F(2) resource population derived from a cross between two broiler lines that differed in their resistance. Two SNP effects reached 5% Bonferroni genome-wide significance (P<1.26×10(-6)). These two SNPs, rs15354805 and rs15355555, were both on chicken (Gallus gallus) chromosome 1 and spanned approximately 600 Kb, from 100.4 Mb to 101.0 Mb. Rs15354805 is in intron 7 of the chicken Roundabout, axon guidance receptor, homolog 2 (ROBO2) gene, and rs15355555 is located about 243 Kb upstream of ROBO2. Rs15354805 explained 5% of the phenotypic variation in antibody response to NDV, post immunization, in chickens. Rs15355555 had a similar effect as rs15354805 because of its linkage disequilibrium with rs15354805 (r(2)=0.98). CONCLUSION: The region at about 100 Mb from the proximal end of chicken chromosome 1, including the ROBO1 and ROBO2 genes, has a strong effect on the antibody response to the NDV in chickens. This study paves the way for further research on the host immune response to NDV.

Genetic parameters and genome-wide association study of hyperpigmentation of the visceral peritoneum in chickens.

BACKGROUND: Hyperpigmentation of the visceral peritoneum (HVP) has recently garnered much attention in the poultry industry because of the possible risk to the health of affected animals and the damage it causes to the appearance of commercial chicken carcasses. However, the heritable characters of HVP remain unclear. The objective of this study was to investigate the genetic parameters of HVP by genome-wide association study (GWAS) in chickens. RESULTS: HVP was found to be influenced by genetic factors, with a heritability score of 0.33. HVP had positive genetic correlations with growth and carcass traits, such as leg muscle weight (rg = 0.34), but had negative genetic correlations with immune traits, such as the antibody response to Newcastle disease virus (rg = -0.42). The GWAS for HVP using 39,833 single nucleotide polymorphisms indicated the genetic factors associated with HVP displayed an additive effect rather than a dominance effect. In addition, we determined that three genomic regions, involving the 50.5-54.0 Mb region of chicken (Gallus gallus) chromosome 1 (GGA1), the 58.5-60.5 Mb region of GGA1, and the 10.5-12.0 Mb region of GGA20, were strongly associated (P < 6.28 × 10-7) with HVP in chickens. Variants in these regions explained >50% of additive genetic variance for HVP. This study also confirmed that expression of BMP7, which codes for a bone morphogenetic protein and is located in one of the candidate regions, was significantly higher in the visceral peritoneum of Huiyang Beard chickens with HVP than in that of chickens without pigmentation (P < 0.05). CONCLUSIONS: HVP is a quantitative trait with moderate heritability. Genomic variants resulting in HVP were identified on GGA1 and GGA20, and expression of the BMP7 gene appears to be upregulated in HVP-affected chickens. Findings from this study should be used as a basis for further functional validation of candidate genes involved in HVP.

Advances in clinical study of curcumin.

Curcumin has been estimated as a potential agent for many diseases and attracted great attention owing to its various pharmacological activities, including anti-cancer, and anti-inflammatory. Now curcumin is being applied to a number of patients with breast cancer, rheumatoid arthritis, Alzheimer's disease, colorectal cancer, psoriatic, etc. Several clinical trials have stated that curcumin is safe enough and effective. The objective of this article was to summarize the clinical studies of curcumin, and give a reference for future studies.

Formulation and evaluation of microemulsion-based in situ ion-sensitive gelling systems for intranasal administration of curcumin.

The purpose of our study was to develop a microemulsion-based in situ ion-sensitive gelling system for intranasal administration of curcumin. A new microemulsion composition for curcumin was optimized with the simple lattice design. And the microemulsion-based in situ ion-sensitive gelling system consisted of Capryol 90 as oil phase, Solutol HS15 as surfactant, Transcutol HP as cosurfactant and 0.3% DGG solution as water phase. The physicochemical properties such as morphology, droplet size distribution, zeta value and the in vitro release were investigated. In addition, the histological section studies on the reaction between the obtained formulation and nasal mucosa showed that the microemulsion-based in situ ion-sensitive gelling system could not produce obvious damage to nasal mucosa. The pharmacokinetics results showed that the absolute bioavailability of curcumin in the microemulsion-based in situ ion-sensitive gelling system was 55.82% by intranasal administration. And the brain targeting index (BTI) was 6.50, and in the tissue distribution experiment, the value of (AUC(brain)/AUC(blood)) following intranasal administration was higher than that following intravenous administration, suggesting that the obvious brain targeting property by nasal delivery be attributed to a direct nose-to-brain drug transport. It can be concluded that the microemulsion-based in situ gelling as an effective and safe vehicle could greatly enhance the in vivo absorption and facilitate the delivery of curcumin to brain by intranasal administration.

Curcumin loaded mixed micelles composed of Pluronic P123 and F68: preparation, optimization and in vitro characterization.

In this study, curcumin (Cur) loaded mixed micelles (Cur-PF), composed of Pluronic P123 (P123) and Pluronic F68 (F68), was prepared using the thin-film hydration method and evaluated in vitro. The preparation process was optimized with a central composite design (CCD). The average size of the mixed micelles was 68.2 nm, and the encapsulating efficiency for Cur was 86.93%, and 6.996% for drug-loading. Compared with the Cur propylene glycol solution, the in vitro release of Cur from Cur-PF presented the sustained-release property. The in vitro cytotoxicity assay showed that the IC(50) values on MCF-7 cells for Cur-PF and free Cur in DMSO solution were 5.04 µg/mL and 8.35 µg/mL, while 2.52 µg/mL and 8.27 µg/mL on MCF-7/ADR cells. It could be concluded from the results that P123/F68 mixed micelles might serve as a potential nanocarrier to improve the solubility and biological activity of Cur.

A novel folate-modified self-microemulsifying drug delivery system of curcumin for colon targeting.

BACKGROUND: The objective of this study was to prepare, characterize, and evaluate a folate-modified self-microemulsifying drug delivery system (FSMEDDS) with the aim to improve the solubility of curcumin and its delivery to the colon, facilitating endocytosis of FSMEDDS mediated by folate receptors on colon cancer cells. METHODS: Ternary phase diagrams were constructed in order to obtain the most efficient self-emulsification region, and the formulation of curcumin-loaded SMEDDS was optimized by a simplex lattice experiment design. Then, three lipophilic folate derivatives (folate-polyethylene glycol-distearoylphosphatidylethanolamine, folate-polyethylene glycol-cholesteryl hemisuccinate, and folate-polyethylene glycol-cholesterol) used as a surfactant were added to curcumin-loaded SMEDDS formulations. An in situ colon perfusion method in rats was used to optimize the formulation of FSMEDDS. Curcumin-loaded FSMEDDS was then filled into colon-targeted capsules and the in vitro release was investigated. Cytotoxicity studies and cellular uptake studies was used in this research. RESULTS: The optimal formulation of FSMEDDS obtained with the established in situ colon perfusion method in rats was comprised of 57.5% Cremophor(®) EL, 32.5% Transcutol(®) HP, 10% Capryol™ 90, and a small amount of folate-polyethylene glycol-cholesteryl hemisuccinate (the weight ratio of folate materials to Cremophor EL was 1:100). The in vitro release results indicated that the obtained formulation of curcumin could reach the colon efficiently and release the drug immediately. Cellular uptake studies analyzed with fluorescence microscopy and flow cytometry indicated that the FSMEDDS formulation could efficiently bind with the folate receptors on the surface of positive folate receptors cell lines. In addition, FSMEDDS showed greater cytotoxicity than SMEDDS in the above two cells. CONCLUSION: FSMEDDS-filled colon-targeted capsules are a potential carrier for colon delivery of curcumin.