[Establishment of a novel co-cultured liver cancer model based on tumor microenvironment].

Objective: To construct a new co-cultured liver cancer research model composed of activated hepatic stellate cells (aHSC) and liver cancer cells, explore the efficacy difference between it and traditional model, so as to establish a liver cancer research model in vitro and in vivo that can reflect the real clinical efficacy. Methods: A new co-culture model of liver cancer consisting of aHSC and liver cancer cells was constructed. The differences in efficacy between the new co-culture model and the traditional single cell model were compared by cytotoxicity test, cell migration test, drug retention test and in vivo tumor inhibition test. Western blot was used to detect the drug-resistant protein P-gp and epithelial-mesenchymal transition-related proteins. Masson staining was used to observe the deposition of collagen fibers in tumor tissues of tumor-bearing mice. CD31 immunohistochemical staining was used to observe the microvessel density in tumor tissues of tumor-bearing mice. Results: The cytotoxicity of single cell model and co-culture model was dose-dependent. With the increase of curcumin (CUR) concentration, the cell viability decreased, but the cell viability of single cell model decreased faster than that of co-culture model. When the concentration of CUR was 10 µg/ml, the cell viability of the co-culture model was 62.3% and the migration rate was (28.05±3.68)%, which were higher than those of the single cell model [38.5% and (14.91±5.92)%, both P<0.05]. Western blot analysis showed that the expressions of P-gp and vimentin were up-regulated in the co-culture model, which were 1.55 and 2.04 fold changes of the single cell model, respectively. The expression of E-cadherin was down-regulated, and the expression level of E-cadherin in the single cell model was 1.17 fold changes of the co-culture model. Drug retention experiment showed that the co-culture model could promote drug efflux and reduce drug retention. In vivo tumor inhibition experiment showed that the m-HSC+ H22 co-transplantation model had faster tumor growth and larger tumor volume than those of the H22 single cell transplantation model. After CUR treatment, the tumor growths of m-HSC+ H22 co-transplantation model and H22 single cell transplantation model were inhibited. Masson staining showed that the deposition of collagen fibers in tumor tissues of m-HSC+ H22 co-transplantation model mice was more than that of H22 single cell transplantation model. CD31 immunohistochemical staining showed that the microvessel density in tumor tissue of m-HSC+ H22 co-transplantation model was higher than that of H22 single cell transplantation model. Conclusions: The aHSC+ liver cancer cell co-culture model has strong proliferation and metastasis ability and is easy to be resistant to drugs. It is a new type of liver cancer treatment research model superior to the traditional single cell model.

[Circular RNA expression profiles and circRNA-miRNA-mRNA crosstalk in pre-eclamptic placenta].

Objective: To identify the expression profile of circular RNA (circRNA) in placenta of pre-eclampsia (PE) pregnant women by high-throughput sequencing, and to construct the circRNA-microRNA (miRNA)-messenger RNA (mRNA) interaction network, so as to reveal the related pathways and regulatory mechanisms of PE. Methods: The clinical data and placentas of 42 women with PE (PE group) and 30 normal pregnant women (control group) who delivered in West China Second University Hospital from November 2019 to June 2021 were collected. (1) High-throughput sequencing was used to establish the differentially expressed circRNA profiles in placental tissues of 5 pairs of PE group and the control group. (2) Real-time quantitative PCR (qRT-PCR) was used to verify the expression levels of 6 differentially expressed circRNAs in placental tissues of PE group and control group. (3) Bioinformatics analysis was used to predict the target miRNA and analyze the co-expressed mRNA to construct a competitive endogenous RNA (ceRNA) network. The differentially expressed circRNAs were analyzed by Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathways. (4) Logistic regression analysis, Pearson correlation and Kendall's tau-b correlation analysis were used to test the correlation between the three differentially expressed circRNAs and the risk of PE and clinical characteristics. (5) circRNA_05393 was selected for subsequent functional study. Small interfering RNA (siRNA) and overexpression plasmid were used to knock down or increase the expression level of circRNA_05393 in trophoblast cell line HTR-8/SVneo cells, respectively. Transwell assay was used to detect the migration and invasion ability of the trophoblasts in vitro. Cell counting kit-8 assay was used to detect the proliferation ability of the trophoblasts. Results: (1) Seventy-two differentially expressed circRNAs were identified by high-throughput sequencing, of which 35 were up-regulated and 37 were down-regulated. (2) qRT-PCR showed that compared with the control group, circRNA_00673 (1.306±0.168 vs 2.059±0.242; t=2.356, P=0.021) and circRNA_07796 (1.275±0.232 vs 1.954±0.230; t=2.018, P=0.047) were significantly increased, while circRNA_05393 (1.846±0.377 vs 0.790±0.094; t=3.138, P=0.002) was significantly decreased. (3) The circRNA-miRNA-mRNA interaction network contained 3 circRNAs, 8 miRNAs and 53 mRNAs. GO functional annotation analysis showed that the biological process was mainly enriched in iron ion homeostasis, membrane depolarization during action potential and neuronal action potential. In terms of cellular components, they were mainly enriched in cytoskeleton and membrane components. In terms of molecular function, they were mainly enriched in the activity of voltage-gated sodium channel and basic amino acid transmembrane transporter. KEGG pathway enrichment analysis showed that mRNAs in the interaction network were mainly enriched in complement and coagulation cascade, glycine, serine and threonine metabolism, p53 signaling pathway and peroxisome proliferators-activated receptors (PPAR) signaling pathway. (4) Logistic regression analysis showed that down-regulation of circRNA_05393 expression was a risk factor for PE (OR=0.044, 95%CI: 0.003-0.596; P=0.019). Correlation analysis showed that circRNA_05393 was significantly correlated with systolic blood pressure and diastolic blood pressure in PE pregnant women (both P<0.05). (5) Knock down or overexpression of circRNA_05393 significantly reduced or increased the migration and invasion abilities of HTR-8/SVneo cells (all P<0.05), but had no significant effect on the ability of tube formation and proliferation (all P>0.05). Conclusions: The construction of circRNA expression profile in placenta and the exploration of circRNA-miRNA-mRNA interaction network provide the possibility to reveal the regulatory mechanism of specific circRNA involved in PE. Inhibition of circRNA_05393 may induce the progression of PE by reducing the migration and invasion of trophoblasts.

Protective effects of miRNA-589 on cerebral ischemia-reperfusion injury.

To uncover the potential influence of microRNA-589 (miRNA-589) on cerebral ischemia-reperfusion injury (IRI) and the underlying mechanism, BV2 cells were stimulated by lipopolysaccharide (LPS) or conditioned medium (CM) of primary cortical neurons undergoing oxygen-glucose deprivation (OGD). Regulatory effects of miRNA-589 on the release of inflammatory factors in BV2 cells induced with LPS or CM of primary cortical neurons undergoing OGD were detected by quantitative real-time polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA). The interaction between miRNA-589 and TRAF6 was finally assessed by dual-luciferase reporter gene assay. MiRNA-589 was downregulated in BV2 cells induced with LPS or CM of primary cortical neurons undergoing OGD. Overexpression of miRNA-589 reduced the release of inflammatory factors in LPS or CM-induced BV2 cells. TRAF6 was verified to be the downstream gene of miRNA-589, and its level was negatively regulated by miRNA-589. MiRNA-589 is downregulated following cerebral IRI and alleviates inflammatory response through negatively regulating TRAF6.

Identification and characterization of a gene involved in the encapsulation response of Helicoverpa armigera haemocytes.

Encapsulation is a kind of cellular immune response of insect haemocytes, which results in the formation of capsules around invading parasites. However, the molecular mechanism of this response is largely unknown. In this study, we identified a potential immune-related gene in the cotton bollworm, Helicoverpa armigera, called defence protein 1 (Ha-DFP1). A tissue distribution analysis revealed that Ha-DFP1 protein was expressed in haemocytes and secreted into the haemolymph of Helic. armigera larvae. The Ha-DFP1 mRNA transcript level in haemocytes and the concentration of the Ha-DFP1 protein in haemolymph both increased after injecting chromatography beads. Purified recombinant Ha-DFP1 bound to the surface of haemocytes and promoted haemocyte encapsulation on chromatography beads in vitro. The spreading ability of haemocytes was inhibited when Ha-DFP1 expression in Helic. armigera larval haemocytes decreased in response to the injection of double-stranded RNA specific to Ha-DFP1, and the encapsulation ability of haemocytes was impaired. Based on these results, we speculate that Ha-DFP1 plays an important role in the Helic. armigera encapsulation response, possibly by binding to the haemocyte surface and mediating spreading behaviour.

Altered corticostriatal functional connectivity in individuals with high social anhedonia.

BACKGROUND: Dysregulation of the striatum and altered corticostriatal connectivity have been associated with psychotic disorders. Social anhedonia has been identified as a predictor for the development of schizophrenia spectrum disorders. The aim of the present study was to examine corticostriatal functional connectivity in individuals with high social anhedonia. METHOD: Twenty-one participants with high social anhedonia score and 30 with low social anhedonia score measured by the Chinese version of the Revised Social Anhedonia Scale were recruited from university undergraduates (age 17-21 years) to undergo resting-state functional MRI scans. Six subdivisions of the striatum in each hemisphere were defined as seeds. Voxel-wise functional connectivity analyses were conducted between each seed and the whole brain voxels, followed by repeated-measures ANOVA for the group effect. RESULTS: Participants with high social anhedonia showed hyper-connectivity between the ventral striatum and the anterior cingulate cortex and the insula, and between the dorsal striatum and the motor cortex. Hypo-connectivity in participants with high social anhedonia was also observed between the ventral striatum and the posterior cingulate cortex. Partial correlation analyses further showed that the functional connectivity between the ventral striatum and the prefrontal cortex was associated with pleasure experience and emotional suppression. CONCLUSIONS: Our findings suggest that altered corticostriatal connectivity can be found in participants with high levels of social anhedonia. Since social anhedonia has been considered a predictor for schizophrenia spectrum disorders, our results may provide novel evidence on the early changes in brain functional connectivity in at-risk individuals.

Genetic diversity and classification of Oryza sativa with emphasis on Chinese rice germplasm.

Despite extensive studies on cultivated rice, the genetic structure and subdivision of this crop remain unclear at both global and local scales. Using 84 nuclear simple sequence repeat markers, we genotyped a panel of 153 global rice cultivars covering all previously recognized groups and 826 cultivars representing the diversity of Chinese rice germplasm. On the basis of model-based grouping, neighbour-joining tree and principal coordinate analysis, we confirmed the widely accepted five major groups of rice cultivars (indica, aus, aromatic, temperate japonica and tropical japonica), and demonstrated that rayada rice was unique in genealogy and should be treated as a new (the sixth) major group of rice germplasm. With reference to the global classification of rice cultivars, we identified three major groups (indica, temperate japonica and tropical japonica) in Chinese rice germplasm and showed that Chinese temperate japonica contained higher diversity than that of global samples, whereas Chinese indica and tropical japonica maintained slightly lower diversity than that present in the global samples. Particularly, we observed that all seasonal, drought-tolerant and endosperm types occurred within each of three major groups of Chinese cultivars, which does not support previous claims that seasonal differentiation exists in Indica and drought-tolerant differentiation is present in Japonica. It is most likely that differentiation of cultivar types arose multiple times stemming from artificial selection for adaptation to local environments.

Intradiscal steroid injection for the treatment of chronic non-specific low back pain in patients with Modic type 1 change.

OBJECTIVE: The aim of this study was to evaluate and aggregate the evidence from the published studies to determine the effectiveness of intradiscal steroid injection (ISI) in patients with symptomatic Modic type I change (MCI). MATERIALS AND METHODS: A systematic literature search was independently performed by two authors. The electronic database, including PubMed, Embase, the Cochrane Library, and Web of Science, were searched with the given search terms but without language restriction. The studies that met the inclusion criteria were included. The relevant data were extracted, and two authors independently assessed the quality of the included studies. We performed the present study using the STATA software package. RESULTS: The present work included seven studies with 434 patients with chronic low back pain (CLBP). The risk of bias in the included randomized controlled trials (RCTs) was rated from low to unclear, and all the included observational studies were rated as high quality. The result of the meta-analysis revealed that there were significant differences in pain intensity [standardized mean difference (SMD): 3.09, 95% confidence interval (CI): 1.60-4.58; p<0.01] and self-assessed improvement/satisfaction [odds ratio (OR): 11.41, 95% CI: 3.39-38.41; p=0.05] after ISI compared to before treatment. However, no significant differences in the proportion of patients with full or part-time employment (OR: 1.03, 95% CI: 0.55-1.91; p>0.05), receiving additional care for CLBP (OR: 0.78, 95% CI: 0.36-1.71; p>0.05), and serious adverse events (OR: 1.09, 95% CI: 0.58 to 2.05; p>0.05) were detected between the groups. CONCLUSIONS: Among CLBP patients with MCI, the use of ISI was significantly associated with a reduction in pain intensity in the short term.

Human leukocyte antigen F (HLA-F). An expressed HLA gene composed of a class I coding sequence linked to a novel transcribed repetitive element.

We describe here the isolation and sequencing of a previously uncharacterized HLA class I gene. This gene, HLA-5.4, is the third non-HLA-A,B,C gene characterized whose sequence shows it encodes an intact class I protein. RNase protection assays with a probe specific for this gene demonstrated its expression in B lymphoblastoid cell lines, in resting T cells, and skin cells, while no mRNA could be detected in the T cell line Molt 4. Consistent with a pattern of expression different from that of other class I genes, DNA sequence comparisons identified potential regulator motifs unique to HLA-5.4 and possibly essential for tissue-specific expression. Protein sequence analysis of human and murine class I antigens has identified 10 highly conserved residues believed to be involved in antigen binding. Five of these are altered in HLA-5.4, and of these, three are nonconservative. In addition, examination of the HLA-5.4 DNA sequence predicts that the cytoplasmic segment of this protein is shorter than that of the classical transplantation antigens. The 3' untranslated region of the HLA-5.4 gene contains one member of a previously undescribed multigene family consisting of at least 30 members. Northern analysis showed that several of these sequences were transcribed, and the most ubiquitous transcript, a 600-nucleotide polyadenylated mRNA, was found in all tissues and cells examined. This sequence is conserved in the mouse genome, where a similar number of copies were found, and one of these sequences was also transcribed, yielding a 600-nucleotide mRNA. The characterization of this unique HLA class I gene and the demonstration of its tissue-specific expression have prompted us to propose that HLA-5.4 be designated HLA-F.

Antidepressant effect of Yueju-Wan ethanol extract and its fractions in mice models of despair.

AIM OF THE STUDY: Yueju-Wan (YJ), a traditional Chinese medicinal formula, is commonly used for the treatment of depression-related syndromes in China. This study was conducted to evaluate the antidepressant activity of YJ ethanol extract (YJ-E) and its four different fractions, the petroleum ether fraction (YJ-EA), ethyl acetate fraction (YJ-EB), n-butanol fraction (YJ-EC) and final aqueous fraction (YJ-ED). MATERIALS AND METHODS: Two experimental despair animal models: the mice tail suspension test (TST) and the mice forced swimming test (FST) were used to evaluate the antidepressant activity of YJ-E and its fractions. These extracts or fractions were administered orally for 7 days, while the parallel positive control was given at the same time using fluoxetine hydrochloride (FLU) in TST and imipramine hydrochloride (IMI) in FST respectively. RESULTS: YJ-E high dose (YJ-E2), YJ-EA, YJ-EC and the positive control groups could decrease the duration of immobility in the TST and FST and have no significant changes in locomotor activity. YJ-E low dose (YJ-E1), YJ-EB, YJ-ED and the vehicle solvent (VEH) control group have no obvious effect on these same tests. CONCLUSIONS: In these despair animal models, YJ ethanol extract, the petroleum ether fraction and n-butanol fraction show potent antidepressant effects. The petroleum ether fraction and n-butanol fraction appear to be the active fractions of YJ-E.

miR-497 promotes the progression of cutaneous squamous cell carcinoma through FAM114A2.

OBJECTIVE: To explore the possible role and mechanism of miR-497 in cutaneous squamous cell carcinoma. PATIENTS AND METHODS: Quantitative Real-time polymerase chain reaction (qRT-PCR) was used to detect miR-497 and FAM114A2 expression level in 38 cases of cutaneous squamous cell carcinoma (CSCC) and 22 normal skin tissues as well as in CSCC cell lines (A431, HSC-5) and normal cells (HaCaT). MiR-497 effects on cell proliferation and cell cycle were examined by CCK8 assays and flow cytometry. Dual luciferase reporter gene assay was performed to detect the regulating relationship between miR-497 and FAM114A2. In addition, the expression of FAM114A2 after overexpression or knockdown of miR-497 was detected by Western blot to evaluate whether miR-497 could regulate proliferation and cell cycle by regulating the expression of FAM114A2. RESULTS: MiR-497mRNA expression in CSCC tissues and cell lines was markedly lower than that in normal tissues and cells. Meanwhile, FAM114A2 mRNA and protein levels in CSCC tissues were markedly higher when compared to than that in normal tissues. miR-497 overexpression or knockdown could inhibit or promote the cell proliferation and cell cycle of A431, HSC-5. The dual luciferase reporter gene assay suggested that FAM114A2 might be a direct target gene of miR-497, and that FAM114A2 expression had a significant negative correlation with miR-497. Overexpression of miR-497 could inhibit FAM114A2 protein expression. Besides, FAM114A2 knockdown reversed the inhibitory effect of low expression of miR-497 on proliferation rate of A431 or HSC-5 cells. CONCLUSIONS: MiR-497 was lowly expressed in squamous cell carcinoma tissues and cells, which can participate in the regulation of cell proliferation through FAM114A2, thus promoting the progression of CSCC.

[Cross-sectional survey of autism spectrum disorders in children aged 0-6 years in Hainan province].

Objective: To understand the prevalence of autism spectrum disorders (ASD) in children aged 0-6 years old and influencing factors in Hainan province. Methods: A total of 37 862 children aged 0-6 years were selected from 18 counties in Hainan province for a screening by using questionnaire of"warning signs in child development", then field diagnosis was made, and general descriptive statistic analysis was conducted. The prevalence of ASD and related factors were analyzed with χ(2) test and unconditional logistic regression model. Results: Among 37 862 children aged 0-6 years, 235 were diagnosed with ASD, the prevalence of ASD was 0.62% (0.99% in boys, 0.17% in girls), the differences was significant (χ(2)=101.91, P=0.000). The prevalence of ASD increased with age (χ(2)=288.62, P=0.000). The prevalence of ASD was significantly higher in urban area than in other areas (χ(2)=114.77, P=0.000). Factors such as full term pregnancy or not, neonatal asphyxia, father's characteristics, father's habit of chewing areca or smoking, mother's general mood, and mother's induced abortion history were the influencing factors for ASD. Conclusion: The prevalence of ASD in children aged 0-6 years was high in Hainan and was influenced by genetic factors, pregnancy and delivery process, parents unhealthy habit before and during pregnancy and other factors.

Atorvastatin improves cardiac function of rats with chronic cardiac failure via inhibiting Rac1/P47phox/P67phox-mediated ROS release.

OBJECTIVE: To discuss the protective mechanisms of atorvastatin treatment for isoproterenol (ISO)-induced chronic heart failure. MATERIALS AND METHODS: The rats were randomly divided into three groups: normal group (n = 15, age-matched normal adult rats), ISO group (n = 11, ISO induced heart failure) and atorvastatin group (n = 14, ISO induced lesion but received atorvastatin treatment). The cardiac function was evaluated by echocardiography and hemodynamics analysis. In addition, the Rac1 activity in the myocardium and the expression levels of Rac1, p47phox and p67phox were measured by RT-PCR and western blot. RESULTS: Rats in ISO group developed into heart failure with decreased cardiac function. The Rac1, p47phox and p67phox mRNA expressions and ROS release were increased in ISO group. Atorvastatin treatment improved cardiac function of rats with isoproterenol-induced chronic heart failure and decreased the Rac1, p47phox and p67phox mRNA expressions. Also, membrane protein expression of Rac1 and ROS release decreased significantly. CONCLUSIONS: Atorvastatin may improve cardiac function of rats with heart failure via inhibiting Rac1/P47phox/P67phox-mediated ROS release.

Differential expression of HLA-E, HLA-F, and HLA-G transcripts in human tissue.

The data presented here demonstrate that the HLA-G class I gene is unique among the members of the human class I gene family in that its expression is restricted to extraembryonic tissues during gestation. Furthermore, the pattern of HLA-G expression in these tissues changes as gestation proceeds. During first trimester HLA-G is expressed within the placenta and not within the extravillous membrane. At term, the pattern of the HLA-G expression is reversed, extravillous membrane expresses HLA-G while placenta does not. Another non-HLA-A, -B, -C class I gene, HLA-E, is also expressed by extraembryonic tissues. Unlike HLA-G, HLA-E is expressed by both placenta and extravillous membrane at first trimester and at term. These results raise the intriguing possibility that the HLA-G-encoded molecule has a role in embryonic development and/or the fetal-maternal immune response.

BCG in China.

PIP: Remarkable progress has been made in the fight against tuberculosis in China since introduction of Bacille Calmette-Guerin (BCG) vaccine in the early 1930s. Until liberation, the cost of the vaccine was beyond the reach of Chinese workers and peasants. After 1949, however, the People's Government set up courses to train local inoculators and organized antituberculosis clinics. At present, BCG vaccination is available in all of the 29 provinces, municipalities, and auconomous regions on the mainland. As of 1979, 500 million vaccinations had been administered to children under 15 years of age. In Beijing, 2,004,933 newborns have been inoculated. The city's conversion rate is 97%. The method of inoculation is adapted to suit local conditions. Scarification, as opposed to the intradermal method, had been found to be particularly suited to rural areas or vaccination over wide areas where a sufficient supply of syringes and needles is not available. To simplify vaccination procedures, some areas have initiated vaccination without tuberculin testing. In part, the dramatic decrease in tuberculosis incidence in China is due to the better living standards following liberation. However, the role played by BCG vaccination in tuberculosis prevention cannot be underestimated.^ieng

[Application of an artificial neural network in the design of sustained-release dosage forms].

AIM: To use the artificial neural network (ANN) in Matlab 5.1 tool-boxes to predict the formulations of sustained-release tablets. METHODS: The solubilities of nine drugs and various ratios of HPMC: Dextrin for 63 tablet formulations were used as the ANN model input, and in vitro accumulation released at 6 sampling times were used as output. RESULTS: The ANN model was constructed by selecting the optimal number of iterations (25) and model structure in which there are one hidden layer and five hidden layer nodes. The optimized ANN model was used for prediction of formulation based on desired target in vitro dissolution-time profiles. ANN predicted profiles based on ANN predicted formulations were closely similar to the target profiles. CONCLUSION: The ANN could be used for predicting the dissolution profiles of sustained release dosage form and for the design of optimal formulation.

[Measurement of the length of the adult esophagus using a fiberogastroscope: 104 cases].

From May 1979 to July 1985, the length of the esophagus in 104 patients with gastric disease was measured by a WX-C3 type fiberogastroscope. The result of measurement showed that the average length from the upper incisors to the cardia was 44.4 cm, and that from the upper end of the esophagus to the cardia was 28.0 cm. These measurement were respectively 4.4 cm and 3.0 cm longer than the traditional data (P less than 0.01). The difference in the length of the esophagus may be explained on the basis that measurement by rigid esophagoscope is in a straight line, while that by flexible fiberogastroscope is in a curvedline. Positive correlation between the length of the esophagus and the height of body was found in 91.3% of the cases. These data are of importance in the accurate localization of esophageal lesions.

LAPTM4B: a novel cancer-associated gene motivates multidrug resistance through efflux and activating PI3K/AKT signaling.

LAPTM4B (lysosomal protein transmembrane 4 beta) is a newly identified cancer-associated gene. Both of its mRNA and the encoded LAPTM4B-35 protein are significantly upregulated with more than 70% frequency in a wide variety of cancers. The LAPTM4B-35 level in cancer is evidenced to be an independent prognostic factor and its upregulation promotes cell proliferation, migration and invasion, as well as tumorigenesis in nude mice. In contrary, knockdown of LAPTM4B-35 expression by RNA interference (RNAi) reverses all of the above malignant phenotypes. We herein reveal a new role of LAPTM4B-35 in promoting multidrug resistance of cancer cells. Upregulation of LAPTM4B-35 motivates multidrug resistance by enhancement of efflux from cancer cells of a variety of chemodrugs with variant structures and properties, including doxorubicin, paclitaxel and cisplatin through colocalization and interaction of LAPTM4B-35 with multidrug resistance (MDR) 1 (P-glycoprotein, P-gp), and also by activation of PI3K/AKT signaling pathway through interaction of PPRP motif contained in the N-terminus of LAPTM4B-35 with the p85α regulatory subunit of PI3K. The specific inhibitors of PI3K and knockdown of LAPTM4B-35 expression by RNAi eliminate the multidrug resistance effect motivated by upregulation of LAPTM4B-35. In conclusion, LAPTM4B-35 motivates multidrug resistance of cancer cells by promoting drug efflux through colocalization and interaction with P-gp, and anti-apoptosis by activating PI3K/AKT signaling. These findings provide a promising novel strategy for sensitizing chemical therapy of cancers and increasing the chemotherapeutic efficacy through knockdown LAPTM4B-35 expression by RNAi.

Genetic diversity among different clones of the gynogenetic silver crucian carp, Carassius auratus gibelio, revealed by transferrin and isozyme markers.

Genetic diversity among four clones (A, D, E, F) of gynogenetic silver crucian carp was studied using transferrin and isozymes in the blood as markers. Of the five proteins investigated, three (transferrin, esterase and superoxide dismutase) indicated polymorphism and eight polymorphic loci were detected. These loci were probably encoded by codominant alleles and their inheritance patterns were analyzed. Intraclonal homogeneity and interclonal heterogeneity were observed in these clones, which allowed us to infer the clonal nature and evolutionary relationship between them. Clonal diversity in this population of silver crucian carp in China was also compared with data reported from gynogenetic crucian carp in Germany.