Treatment of primary epididymal adenocarcinoma: a case report and review of the literature.

BACKGROUND: Epididymal tumors, especially malignant tumors, have low incidence and are rare in our clinical work. However, they may progress quickly and have poor prognosis. For such rare clinical cases with extremely low incidence rates, and as they are prone to misdiagnosis and missed diagnosis and have a very poor prognosis, clinical workers need to pay special attention and consider the possibility of primary epididymal malignant tumors. CASE REPORT: A 63-year-old Chinese male patient from Asia was admitted due to scrotal pain. Upon examination, an abnormal lesion was found in the right epididymal region. After thorough evaluation, surgical resection was performed, and the postoperative pathological result confirmed the presence of epididymal adenocarcinoma. After further ruling out secondary lesions, primary epididymal adenocarcinoma was considered. Right retroperitoneal lymph node dissection was performed under laparoscopic for treatment, and 1/11 lymph node metastasis was detected after surgery. The patient is currently under close follow-up. CONCLUSIONS: The number of clinical cases of primary epididymal malignant tumors is very limited, there is currently no standardized diagnosis and treatment process, and there is a lack of systematic evaluation methods regarding the effectiveness of different treatment options such as chemotherapy, radiotherapy, immunotherapy, and targeted therapy. In addition, the outcome is difficult to predict. In this article, we reviewed relevant literature and systematically elaborated on the diagnosis and treatment of epididymal malignant tumors, hoping to provide useful information for relevant experts.

SPI1 exacerbates iron accumulation and promotes osteoclast formation through inhibiting the expression of Hepcidin.

BACKGROUND: Osteoporosis (OP) can be caused by an overactive osteoclastic function. Anti-osteoporosis considerable therapeutic effects in tissue repair and regeneration because bone resorption is a unique osteoclast function. In this study, we mainly explored the underlying mechanisms of osteoclasts' effects on osteoporosis. METHODS: RAW264.7 cells were used and induced toward osteoclast and iron accumulation by M-CSF and RANKL administration. We investigated Hepcidin and divalent metal transporter 1 (DMT1) on iron accumulation and osteoclast formation in an ovariectomy (OVX)-induced osteoporosis. Osteoporosis was induced in mice by OVX, and treated with Hepcidin (10, 20, 40, 80 mg/kg, respectively) and overexpression of DMT1 by tail vein injection. Hepcidin, SPI1, and DMT1 were detected by immunohistochemical staining, western blot and RT-PCR. The bioinformatics assays, luciferase assays, and Chromatin Immunoprecipitation (ChIP) verified that Hepcidin was a direct SPI1 transcriptional target. Iron accumulation was detected by laser scanning confocal microscopy, Perl's iron staining and iron content assay. The formation of osteoclasts was assessed using tartrate-resistant acid phosphatase (TRAP) staining. RESULTS: We found that RAW264.7 cells differentiated into osteoclasts when exposed to M-CSF and RANKL, which increased the protein levels of osteoclastogenesis-related genes, including c-Fos, MMP9, and Acp5. We also observed higher concentration of iron accumulation when M-CSF and RANKL were administered. However, Hepcidin inhibited the osteoclast differentiation cells and decreased intracellular iron concentration primary osteoclasts derived from RAW264.7. Spi-1 proto-oncogene (SPI1) transcriptionally repressed the expression of Hepcidin, increased DMT1, facilitated the differentiation and iron accumulation of mouse osteoclasts. Overexpression of SPI1 significantly declined luciferase activity of HAMP promoter and increased the enrichment of HAMP promoter. Furthermore, our results showed that Hepcidin inhibited osteoclast differentiation and iron accumulation in mouse osteoclasts and OVX mice. CONCLUSION: Therefore, the study revealed that SPI1 could inhibit Hepcidin expression contribute to iron accumulation and osteoclast formation via DMT1 signaling activation in mouse with OVX.

Iron accumulation induced by hepcidin1 knockout accelerates the progression of aging osteoporosis.

OBJECTIVE: Iron accumulation is associated with osteoporosis. This study aims to explore the effect of chronic iron accumulation induced by hepcidin1 deficiency on aging osteoporosis. METHODS: Iron accumulation in hepcidin1 knockout aging mice was assessed by atomic absorption spectroscopy and Perl's staining. Bone microarchitecture was observed using Micro-CT. Hepcidin, ferritin, oxidative stress, and markers of bone turnover in serum were detected by enzyme-linked immunosorbent assay. Bone formation and resorption markers were measured by real-time quantitative PCR. Cell aging was induced by D-galactose treatment. CCK-8, flow cytometry, EdU assays, and Alizarin red staining were performed to reveal the role of hepcidin1 knockout in cell model. Iron Colorimetric Assay Kit and western blot were applied to detect iron and ferritin levels in cells, respectively. RESULTS: In hepcidin1-knockout mice, the ferritin and iron contents in liver and tibia were significantly increased. Iron accumulation induced by hepcidin1 knockout caused a phenotype of low bone mass and deteriorated bone microarchitecture. Osteogenic marker was decreased and osteoclast marker was increased in mice, accompanied by increased oxidative stress level. The mRNA expression levels of osteoclast differentiation markers (RANKL, Mmp9, OPG, Trap, and CTSK) were up-regulated, while bone formation markers (OCN, ALP, Runx2, SP7, and Col-1) were down-regulated in model group, compared to wild type mice. In vitro, hepcidin1 knockdown inhibited proliferation and osteogenic differentiation, while promoted apoptosis, with increased levels of iron and ferritin. CONCLUSION: Iron accumulation induced by hepcidin1 deficiency aggravates the progression of aging osteoporosis via inhibiting osteogenesis and promoting osteoclast genesis.

Retroperitoneal lymphoma with double inferior vena cava shown using a 3D visualization model: A case report and literature review.

Cases of a retroperitoneal tumor with double inferior vena cava (IVC) are rarely reported. The present report documents a case of a retroperitoneal lymphoma with double IVC, and discusses its embryological, clinical and radiological significance. In addition, previous cases of a double IVC are reviewed. In the present report, a 52-year-old male patient was hospitalized for a retroperitoneal lymphoma tumor and double IVC. CT urography was performed, whilst a three-dimensional visualization model was also established based on CT data, to reveal a retroperitoneal tumor with double IVC. The present case involved a double IVC with interiliac vein, which was type 2b from the left IVC. The retroperitoneal tumor was identified to be a lymphoma measuring 116x83 mm by percutaneous puncture biopsy. Surgical treatment is generally not recommended for lymphoma. Therefore, this patient was transferred to the Hematology Department for treatment according to the lymphoma management guidelines. The size of the tumor was reduced after chemotherapy during the patient's follow-up. In conclusion, the three-dimensional visualization model can directly and accurately present the anatomical features of the double IVC and its surrounding tissue structure. In addition, variations in the features of IVC can have important clinical significance. It is also important for surgeons, interventional radiologists and clinicians to understand such abnormalities in anatomical features to avoid misdiagnosis and reduce the occurrence of serious intraoperative complications.

[Imbalance of Th17/Tregs promotes egg granuloma formation of liver with Schistosomiasis japonicum in mice].

Objectives To investigate the effect of the imbalance of Th17/Treg on egg granuloma formation of liver with Schistosomiasis japonicum. Methods The BALB/c mice were infected with Schistosoma japonicum cercariae to establish a model of Schistosomiasis japonica. The blood samples, liver tissues and spleen tissue were harvested at the 2nd, 4th, 6th, 8th week, respectively. HE staining and Masson staining were performed to assess the pathological characteristics of the liver. Flow cytometry (FCM) was conducted to evaluate the proportion of CD4+ T cell subsets including Th17 cells and Tregs in liver and spleen tissue. The quantitative real-time PCR (qRT-PCR) was carried out to investigate the mRNA level of cytokines including RORγt, FOXP3, IL-6, IL-17, IL-23 and IL-10 in liver tissues. Finally, ELISA was performed to assess the serum level of cytokines including IL-6, IL-17, IL-23 and TGF-ß. Schistosoma japonicium soluble egg antigen (SjSEA) were prepared to stimulate mouse spleen cells in vitro. qRT-PCR was carried out to investigate the mRNA level of cytokine including RORγt and FOXP3 and ELISA was performed to assess the expression level of cytokines including IL-6, IL-17, IL-23 and TGF-ß at different time points. Results HE and Masson staining demonstrated that inflammatory cell infiltration, schistosome egg granuloma formation and the collagen deposition increased in the liver tissue after the 4th week. The longer the infection, the more severe the liver pathology. In the liver and spleen tissues, the percentage of Th17 cells of infection group (2nd, 4th and 6th weeks) were significantly higher than the healthy group. The percentage of Tregs in the liver tissues of infection group (4th, 6th and 8th weeks) were significantly higher than the healthy group, and the percentage of Tregs in the spleen of infection group (2nd and 4th weeks) were significantly higher than the healthy group. Th17/Treg ratios in the liver of infection group were lower than the healthy group. Th17/Treg ratios in the spleen of infection group (2nd and 4th weeks) were lower than the healthy group, while it increased in the 6th week. At the same time, the levels of Th17 cells and Tregs related nuclear transcription factors and cytokines showed similar dynamic changes as the percentages of T cell subsets. SjSEA can induce the differentiation of Th17 and Tregs and the expression of related cytokines and transcription factors. Conclusion Th17 cells may play a major role in liver pathology, and the imbalance of Th17 cells/Tregs was closely related to the schistosome egg granuloma formation.

Long non-coding RNA-small nucleolar RNA host gene 7 regulates inflammatory responses following spinal cord injury by regulating the microRNA-449a/TNF-α-induced protein 3-interacting protein 2 axis.

The current study aimed to explore the anti-inflammatory effects of long non-coding RNA-small nucleolar RNA host gene 7 (lncRNA-SNHG7) and its mechanism in spinal cord injury (SCI) models. SCI models were established both in vivo and in vitro. Reverse transcription-quantitative PCR was performed to determine the expression levels of lncRNA-SNHG7 in SCI models. Bioinformatics analysis and dual-luciferase reporter assays were carried out to confirm the interaction between lncRNA-SNHG7 with microRNA (miR)-499a and TNF-α-induced protein 3-interacting protein 2 (TNIP2). In addition, cell viability, apoptosis, and the secretion of inflammatory cytokines were assessed by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay, flow cytometric analysis, and enzyme linked immunosorbent assay (ELISA), respectively. The results showed that lncRNA-SNHG7 was markedly downregulated in the SCI model group. LncRNA-SNHG7 directly bound to miR-499a, which in turn directly targeted TNIP2. In addition, TNIP2 was significantly decreased in SCI rats and lipopolysaccharide (LPS)-treated PC-12 cells. The in vitro results in PC-12 cells revealed that lncRNA-SNHG7 overexpression attenuated neuronal cell death and SCI-mediated inflammatory responses by regulating miR-449a expression. Furthermore, miR-499a knockdown inhibited LPS-induced PC-12 cell injury by targeting TNIP2. In conclusion, lncRNA-SNHG7 modulates the apoptosis and inflammation of PC-12 cells by regulating the miR-449a/TNIP2/NF-κB signaling pathway.

Changes in tumor suppressors and inflammatory responses during hydrogen peroxide-induced senescence in rat fibroblasts.

Cell proliferation and senescence are processes induced by oxidative stress. In this study, we aimed to establish a cellular model of rapid proliferation and senescence of rat tail-tip fibroblasts by hydrogen peroxide (H2O2), a well-known oxidant. On this basis, changes in oxidative stress, inflammatory response and cell cycle of fibroblasts were studied. After H2O2 treatment, cell counting and flow cytometry results showed that 50 µM of H2O2 for 12 h and 100 µM for 8 h effectively promoted fibroblast proliferation, while 500 µM rapidly led to cell cycle arrest. In addition, stimulation with H2O2 at a concentration of 50 µM also promoted the inflammatory effects of the cells. At a concentration of 100 µM H2O2, the cellular antioxidant system began to collapse at 8 h and began to affect cellular activity. 500 µM of H2O2 at 4 h the levels of senescence-associated ß-galactosidase, a marker of senescence and oxidative stress, were almost positive in fibroblasts. In addition, we found that the risk of fibroblasts carcinogenesis increased with increased H2O2 stimulation. The results of this study indicate that H2O2 can cause rapid proliferation and senescence of fibroblasts and that its mechanism of action may be mainly through influencing cellular antioxidant systems, cellular inflammatory responses and cell cycle.

To explore the clinical efficacy of Traditional Chinese Medicine bath in the treatment of psoriasis vulgaris with blood-heat syndrome and its effect on related cytokines based on different temperature and different concentration.

BACKGROUND: Chinese herbal bath has long been used in the curative treatment of psoriasis vulgaris. However, there is no unified standard protocol for Chinese herbal bath. Many factors affect the curative effect of Chinese herbal bath, such as water temperature, bath concentration, and soaking time. Most studies involving Chinese herbal bath has described the bath generally, and few studies have investigated the factors that might contribute to the efficacy of Chinese herbal bath. Here we describe a protocol to evaluate the efficacy and safety of various bathwater temperatures and herbal concentrations on psoriasis vulgaris, and their effect on serum vascular endothelial growth factor (VEGF), tumor necrosis factor α (TNF-α), interleukin 23 (IL-23), and interleukin 17 (IL-17). These data could be useful for optimizing Chinese herbal bath treatments. METHODS: In this randomized controlled trial, we planned to recruit 288 hospitalized atients with psoriasis vulgaris aged 18 to 65 years. All participants who meet the inclusion criteria will be randomly assigned to the observation group, the control group, or the basic treatment group. The observation group will be divided into 6 sub-groups according to water temperatures and bath concentrations, designated as observation groups 1 to 6. Thirty-six participants will be assigned to each group. The basic treatment group will be given co-qingdai capsule, po 2 g tid; compound glycyrrhizin tablet, po 75 mg tid; AA Skincare jojoba Oil, us.ext qd. The observation group will be given a Chinese herbal bath at the same time as the basic treatment. The control group will be given ozone hydrotherapy at the same time as the basic treatment. The entire treatment course will last for 2 weeks. The following parameters will be compared in each group, before and 2 weeks after treatment: the psoriasis area and severity index score (PASI), pruritus score, clinical efficacy, and dermatology life quality index score (DLQI); serum levels of serum VEGF, TNF-α, IL-23, and IL-17; and confocal laser scanning microscope images. CONCLUSION: This study will evaluate the efficacy and safety of various Chinese herbal bath conditions (water temperatures and herbal concentrations) on the treatment of psoriasis vulgaris, which will provide an important reference for the operation of Chinese herbal bath. TRIAL REGISTRATION NUMBER: ChiCTR1900027468.

Hydroxyapatite-embedded monolithic column for selective on-line solid-phase extraction of adenosine triphosphate and its phosphorylated metabolites.

A novel hydroxyapatite-embedded monolithic column has been facilely prepared in a stainless-steel column with inner diameter of 2.1 mm by the strong adhesion of urea-formaldehyde (UF) resin and exploited as a sorbent for selective on-line solid-phase extraction (on-line SPE) of adenosine triphosphate and its phosphorylated metabolites. The composition for this preparation, including the amount of hydroxyapatite nanopowders and the porogen were investigated to obtain a suitable monolith with large surface area and satisfactory permeability. Owing to anion exchange interaction of hydroxyapatite and hydrophilic interaction of UF monolithic matrix, the prepared monolith showed good extraction efficiency and selectivity towards these phosphorylated analytes. Several parameters for on-line SPE, including ACN percentage in the sampling solution, collection time span, salt concentration of the eluent, sampling and elution flow rate, were optimized with respect to the extraction efficiencies of the target compounds. Under the optimized conditions, the LODs of the analytes were in the range of 0.01-0.04 µg/g, the recoveries in the spiked samples ranged from 78.3%-92.5% with RSDs <4.7%. Due to the excellent extraction ability towards phosphorylated compounds in practical samples, a simple on-line SPE-HPLC method using hydroxyapatite-embedded monolith as sorbent has been proposed for monitoring freshness of grass carp.

Effects of Tiletamine-xylazine-tramadol Combination and its Specific Antagonist on AMPK in the Brain of Rats.

INTRODUCTION: Tiletamine-xylazine-tramadol (XFM) has few side effects and can provide good sedation and analgesia. Adenosine 5'-monophosphate-activated protein kinase (AMPK) can attenuate trigeminal neuralgia. The study aimed to investigate the effects of XFM and its specific antagonist on AMPK in different regions of the brain. MATERIAL AND METHODS: A model of XFM in the rat was established. A total of 72 Sprague Dawley (SD) rats were randomly divided into three equally sized groups: XFM anaesthesia (M group), antagonist (W group), and XFM with antagonist interactive groups (MW group). Eighteen SD rats were in the control group and were injected intraperitoneally with saline (C group). The rats were sacrificed and the cerebral cortex, cerebellum, hippocampus, thalamus, and brain stem were immediately separated, in order to detect AMPKα mRNA expression by quantitative PCR. RESULTS: XFM was able to increase the mRNA expression of AMPKα1 and AMPKα2 in all brain regions, and the antagonist caused the opposite effect, although the effects of XFM could not be completely reversed in some areas. CONCLUSION: XFM can influence the expression of AMPK in the central nervous system of the rat, which can provide a reference for the future development of anaesthetics for animals.

Comparison of the effects of exercise with chondroitin sulfate on knee osteoarthritis in rabbits.

BACKGROUND: The aim of the study is to compare the effects of exercise therapy with chondroitin sulfate (CS) therapy in an experimental model of osteoarthritis (OA). METHODS: Twenty-one New Zealand rabbits were randomly divided into four groups: normal group (N group, n = 3); OA control group (C group, n = 6); OA plus medication group (CS group, n = 6); and OA plus exercise group (E group, n = 6). Four weeks after modeling, the rabbits were subjected to exercise (artificial, 30 min/time, 4 times/week) or medicated with CS (2% CS, 0.3 ml/time, once/week) for 4 weeks. Histopathological changes in treated joints were examined after staining. X-ray and scanning electron microscopy was used to evaluate the different therapies by examining the surfaces and joint spaces of the articular cartilage. RT-qPCR was used to assess chondrogenic gene expression including Col2, Col10, mmp-13, il-1ß, adamats-5, and acan in the experimental groups. RESULTS: Histology showed both treatment groups resulted in cartilage that was in good condition, with increased numbers of chondrocytes, and the results of X-ray and scanning electron microscopy showed the therapeutic effect of exercise therapy is equivalent to CS therapy, surface articular cartilage was flat, and the of cartilage layer was thinning. All treated groups induced the expression of Col10 and Col2 and decreased expression of mmp-13, il-1ß, and adamats-5 compared with the control groups. The expression of acan was upregulated in the E group and downregulated in the CS group. Furthermore, expression of Col10 was higher and il-1ß was lower in the exercise group compared to that of the CS group. CONCLUSION: These results indicate that exercise has a positive effect on OA compare with CS, and it also supplies reference for the movement mode to improve function.

Identification of a protein associated with the activity of cytokine-induced killer cells.

Cytokine-induced killer cells (CIKs) adoptive immunotherapy for efficient antitumor ability is used clinically, but details regarding the proteins associated with CIK activity remain unclear. In the current study, the cytotoxicity of CIKs on hepatoma was identified to be significantly downregulated by 1.61-fold following gentamincin treatment. Further research revealed that a differentially expressed protein (P43) was significantly downregulated by 1.22-fold using one-dimensional gel electrophoresis analysis. Of these, the P43 was identified as human haptoglobin using liquid chromatography-mass spectrometry. Western blotting demonstrated that the haptoglobin specifically reacted with rabbit anti-human-haptoglobin. Furthermore, western blotting results verified that the haptoglobin was significantly downregulated by 1.17-fold compared with the control group. In addition, the expression of haptoglobin mRNA was significantly downregulated by 1.73-fold following gentamincin treatment. Taken together, the results of the present study demonstrated that the expression of haptoglobin protein was associated with the activity of CIKs, and the results will be beneficial to the further investigation of CIK activity-enhancement mechanism.

Protective effect of the ω-3 polyunsaturated fatty acids on the schistosomiasis liver fibrosis in mice.

This study aims to observe the effect of ω-3 polyunsaturated fatty acids on initiation and elimination of the schistosomiasis inflammatory response and liver fibrosis. The mice infected with the cercariae of Schistosoma japonicum (20 ± cercarie per mice) were separated randomly into several groups. After 60 days, liver tissue samples of all mice were sectioned. Hematoxylin-eosin (HE) staining, Masson staining, the enzyme-linked immunosorbent assay (ELISA), and flow cytometry (FCM) were performed. Through HE and Masson staining, the size of egg (ovum) granuloma and the collagen deposited in mice's livers in ω-3 PUFAs and praziquantel mixed groups were less than that of model group and praziquantel treated group. The serum level of IL-13 and TNF-α were lower than that of model group and praziquantel treated group. The indicators of liver fibrosis, such as HA and LN in the group treated with ω-3 PUFAs and praziquantel before the release of soluble eggs antigen (SEA) into blood, were lower than that of model group and praziquantel treated group, respectively. The combined treatment of ω-3 polyunsaturated fatty acids and praziquantel conducted before the release of soluble eggs antigens into the blood decreases liver ovum granulomatous inflammation and fibrosis degree in the schistosomiasis. The mechanism of the ω-3 polyunsaturated fatty acid may be related to the adjustment of the anti-inflammatory and immune responses.

mTOR regulates TLR-induced c-fos and Th1 responses to HBV and HCV vaccines.

Although IL-12 plays a critical role in priming Th1 and cytotoxic T lymphocyte (CTL) responses, Toll-like receptor (TLR) signaling only induces low amounts of IL-12 in dendritic cells and macrophages, implying the existence of stringent regulatory mechanisms. In this study, we sought to uncover the mechanisms underlying TLR-induced IL-12 expression and the Th1 response. By systemic screening, we identified a number of protein kinases involved in the regulation of TLRinduced IL-12 expression. In particular, PI3K, ERK, and mTOR play critical roles in the TLR-induced Th1 response by regulating IL-12 and IL-10 production in innate immune cells. Moreover, we identified c-fos as a key molecule that mediates mTOR-regulated IL-12 and IL-10 expression in TLR signaling. Mechanistically, mTOR plays a crucial role in c-fos expression, thereby modulating NFκB binding to promoters of IL-12 and IL-10. By controlling the expression of a special innate gene program, mTOR can specifically regulate the TLR-induced T cell response in vivo. Furthermore, blockade of mTOR by rapamycin efficiently boosted TLR-induced antigen-specific T and B cell responses to HBV and HCV vaccines. Taken together, these results reveal a novel mechanism through which mTOR regulates TLR-induced IL-12 and IL-10 production, contributing new insights for strategies to improve vaccine efficacy.

Polymorphisms and haplotypes of the TGF-ß1 gene are associated with risk of polycystic ovary syndrome in Chinese Han women.

OBJECTIVES: Transforming growth factor-beta 1 (TGF-ß1) is one of the multifunctional cytokine families. It takes part in a series of physiological and pathological processes in the human body, including wound healing, tissue fibrosis and embryonic development. Recent studies have shown that TGF-ß1 participates in the development of polycystic ovary syndrome (PCOS). This study was therefore designed to investigate the association of TGF-ß1 polymorphism with the risk of PCOS. STUDY DESIGN: We enrolled 328 PCOS patients and 358 healthy individuals in this study. Five single nucleotide polymorphisms (SNPs) - rs4803457C/T, rs11466313 deletion/AGG, rs2217130C/T, rs1800469C/T and rs1800470C/T - were detected using Snapshot technology. Linkage disequilibrium and haplotype analysis was conducted among the five SNPs. The relationship between genotypes and haplotypes and the risk of PCOS was also explored. RESULTS: The TT/CT/CC genotype frequencies of rs4803457 in the PCOS group and the control group were 0.2805/0.4878/0.2317 and 0.3659/0.4749/0.1592 respectively. The C/T allele frequencies in the PCOS group and control group were 0.3813/0.6187 and 0.3966/0.6034 respectively. There were significant differences in genotype distribution frequencies and allele frequencies between these two groups (P=0.018). Logistic regression analysis showed that CC genotype had higher risk of PCOS than the no CC genotype in rs4803457 loci (OR=1.75, 95%CI=1.11-2.75). Haplotype analysis further showed that the haplotypes "T-del-C-C-C", "C-del-C-C-C" and "C-del-C-T-C" were associated with the highest risk of PCOS. However, for rs11466313 deletion/AGG, rs2217130C/T, rs1800469C/T and rs1800470C/T, no significant association with PCOS risk was observed. CONCLUSION: The TGF-ß1 gene rs4803457C/T polymorphism is associated with susceptibility to PCOS, and is the key contributor for the development of PCOS in Chinese Han women. The haplotypes T-del-C-C-C, C-del-C-C-C and C-del-C-T-C are also risk factors for PCOS susceptibility among Chinese Han women.

Hepatitis B virus induces expression of cholesterol metabolism-related genes via TLR2 in HepG2 cells.

AIM: To investigate whether hepatitis B virus (HBV) exacerbates hepatic cholesterol accumulation, and explore the underlying mechanisms. METHODS: HepG2 cells were infected with adenovirus (Ad) containing 1.3-fold overlength HBV genome. Real-time polymerase chain reaction and Western blotting were used to measure mRNA and protein expression of target genes. Cholesterol accumulation was measured by fluorescence microscopy. Cell toxicity due to Ad-HBV treatment was determined by the mitochondrial tetrazolium assay. The protein levels of toll-like receptors (TLRs) were determined by Western blotting. RESULTS: Ad-HBV increased hepatic cholesterol accumulation and enhanced the mRNA and protein levels of low-density lipoprotein receptor (LDLR) and 3-hydroxy-3-methylglutharyl-coenzyme A reductase (HMGCoAr) mRNA and protein expression in HepG2 cells. In addition, these inductive effects were partly offset by suppressing TLR2 expression levels by small interfering RNA in HepG2 cells. CONCLUSION: Ad-HBV increases LDLR and HMGCoAr expression, resulting in exacerbated cholesterol accumulation in HepG2 cells, which was mediated via the TLR2 pathway.

Dynamic characteristics of MR diffusion-weighted imaging in a rabbit liver VX-2 tumor model.

PURPOSE: To investigate prospectively dynamic characteristics of the apparent diffusion coefficient (ADC) on MR diffusion-weighted imaging (DWI) in a rabbit VX-2 tumor model. MATERIALS AND METHODS: Forty New Zealand rabbits were included in the study, and 47 rabbit VX-2 tumor models were developed by direct and intrahepatic implantation after opening the abdominal cavities. DWI was carried out periodically and respectively on days 7, 14 and 21 after implantation. The VX-2 tumor samples were studied by pathology. The distinction of VX-2 tumors on DWI was assessed by their ADC values by analysis of variance (ANOVA) using SPSS12.0 software. RESULTS: The ADC values (mean ± SD) × 10(-3) mm(2)/s of 47 VX-2 tumors in the peripheral and central areas were 2.18 ± 0.29, 1.96 ± 0.33, 1.80 ± 0.35, 2.20 ± 0.29, 2.05 ± 0.30 and 1.96 ± 0.48, respectively, on days 7, 14 and 21 after implantation. ADC values of 47 VX-2 tumors in the area of the tumor periphery, center and normal parenchyma were higher when the b-value was 100 s/mm(2) than those when the b-value was 300 s/mm(2) (F = 17.964, p < 0.001; F = 13.986, p < 0.001; F = 128.681, p < 0.001). ADC values in the area of normal liver parenchyma were higher than those in the area of the VX-2 tumor periphery and center when the b-value was 100 or 300 s/mm(2). ADCs of viable tumor cells in VX-2 tumors were lower on DWI than those in the area of normal liver parenchyma around the tumor, and ADCs of dead tumor cells in VX-2 tumors were unequal, including high, equal and low values, but they were higher than in the area of normal liver parenchyma around tumors after dead tumor cells had been liquefied or had become cystic. CONCLUSION: ADC is correlated with the tumor histology and degree of malignancy, and DWI has potential value for dynamically monitoring tumors and evaluating the degree of malignancy and therapeutic effect.

Changes of endoplasmic reticulum and mitochondria in mammary epithelial cells during mammogenesis in Chinese Holstein dairy cows.

The objective of the research was to study the changes of the major organelles, endoplasmic reticulum (ER) and mitochondria, in mammary epithelial cells of the Chinese Holstein dairy cow during mammogenesis. For this purpose, a mammary epithelial cell bank was established from 9 selected Chinese Holstein dairy cows using collagenase I digestion and attachment culture biotechniques. This cell bank included 9 samples at stages of pregnancy, lactation and involution. The changes of ER and mitochondria in the mammary cells were observed at the subcellular level using living cell fluorescent labeling and laser confocal microscopy. Subsequently, the area of integrated optical density of each sample was calculated to determine changes of ER and mitochondria in the mammary epithelial cells. The results showed clear differences in the epithelial major organelles during the various mammary gland development stages. The ER and mitochondria, as an indicator of lactogenic activity of alveolar secretory cells, increased in number from pregnancy to lactation by an average 37.32% and 18.44%, respectively, which was followed by a reduction at involution by an average 38.04% and 22.91% compared to lactation. Our study shows that the stages of mammogenesis are accompanied by changes in activity of the major organelles of the mammary epithelial cells.

The kinase activity of interleukin-1 receptor-associated kinase 2 is essential for lipopolysaccharide-mediated cytokine and chemokine mRNA stability and translation.

Interleukin-1 receptor-associated kinase 2 (IRAK2) has been shown to be essential for lipopolysaccharide (LPS)-mediated posttranscriptional control of cytokine and chemokine production. In this study, we investigated the role of IRAK2 kinase activity in LPS-mediated posttranscriptional control by reconstituting IRAK2-deficient macrophages with either wild-type or kinase-inactive IRAK2. Compared with wild-type IRAK2 (IRAK2-WT) macrophages, kinase-inactive IRAK2 (IRAK2-KD) macrophages show reduced cytokine and chemokine mRNA stability and translation in response to LPS. Further, LPS-treated IRAK2-KD macrophages also show reduced activation of MKK3/6, MNK1, and eIF4E and attenuated toll-like receptor 4-induced tristetraprolin modification and stabilization. Taken together, these results suggest that the kinase activity of IRAK2 is required for the optimal activation of mitogen-activated protein kinase signaling, which regulates cytokine and chemokine production at posttranscriptional levels.

Gene expression and MR diffusion-weighted imaging after chemoembolization in rabbit liver VX-2 tumor model.

AIM: To investigate the dynamic characteristics and the correlation between PCNA, Bax, nm23, E-cadherin expression and apparent diffusion coefficient (ADC) on MR diffusion-weighted imaging (DWI) after chemoembolization in rabbit liver VX-2 tumor model. METHODS: Forty New Zealand rabbit liver VX-2 tumor models were included in the study. DWI was carried out periodically after chemoembolization. All VX-2 tumor samples in each group were examined by histopathology and Strept Avidin-Biotin Complex (SABC) immunohistochemical staining. RESULTS: The PCNA expression index in VX-2 tumors was higher than in the normal parenchyma around the tumor (P < 0.001). Nm23, Bax or E-caderin expression index in VX-2 tumors were lower than in the normal parenchyma around the tumor (all P < 0.001). PCNA and nm23 expression in the VX-2 tumor periphery first increased and then decreased (P < 0.001 and P = 0.03, respectively), while the expression of Bax and E-cadherin before and after chemoembolization was insignificant. When b-value was 100 s/mm(2), there was a linear correlation between PCNA expression and ADC in the area of VX-2 tumor periphery (P < 0.001), and PCNA expression in VX-2 tumor periphery influenced the ADC. CONCLUSION: The potential of VX-2 tumor infiltrating and metastasizing decreases, while its ability to proliferate increases for a short time after chemoembolization. To some degree, the ADC value indirectly reflects the proliferation of VX-2 tumor cells.