Chemosensitivity to doxorubicin in primary cells derived from tumor of FVB/N-Trp53tm1Hw1 with TALEN-mediated Trp53 mutant gene.

BACKGROUND: To evaluate the chemosensitivity to doxorubicin (DOX) in two primary cells derived from a tumor of FVB/N-Trp53tm1Hw1 knockout (KO) mice with TALEN-mediated Trp53 mutant gene, we evaluated the cell survivability, cell cycle distribution, apoptotic cell numbers and apoptotic protein expression in solid tumor cells and ascetic tumor cells treated with DOX. RESULTS: The primary tumor cells showed a significant (P < 0.05) defect for UV-induced upregulation of the Trp53 protein, and consisted of different ratios of leukocytes, fibroblasts, epithelial cells and mesenchymal cells. The IC50 level to DOX was lower in both primary cells (IC50 = 0.12 µM and 0.20 µM) as compared to the CT26 cells (IC50 = 0.32 µM), although the solid tumor was more sensitive. Also, the number of cells arrested at the G0/G1 stage was significantly decreased (24.7-23.1% in primary tumor cells treated with DOX, P < 0.05) while arrest at the G2 stage was enhanced to 296.8-254.3% in DOX-treated primary tumor cells compared with DOX-treated CT26 cells. Furthermore, apoptotic cells of early and late stage were greatly increased in the two primary cell-lines treated with DOX when compared to same conditions for CT26 cells. However, the Bax/Bcl-2 expression level was maintained constant in the primary tumor and CT26 cells. CONCLUSIONS: To the best of our knowledge, these results are the first to successfully detect an alteration in chemosensitivity to DOX in solid tumor cells and ascetic tumor cells derived from tumor of FVB/N-Trp53tm1Hw1 mice TALEN-mediated Trp53 mutant gene.

T-cell lymphoma infiltrating the uterus and ovaries of a Golden Retriever: a case report.

BACKGROUND: To the best of our knowledge, this is the first report of female genital system infiltration of T-cell lymphoma in veterinary literature. CASE PRESENTATION: A 1.5-year-old, intact female Golden Retriever was referred due to melena and hyporexia that lasted for three weeks. Fever (40.5℃), tachycardia, tachypnoea, pale mucous membranes, and purulent vaginal discharge were identified on physical examination. Blood analyses revealed leucocytosis, anaemia, hypoalbuminemia, and increased lactate and C-reactive protein levels. On abdominal radiography, the small intestine was moderately deviated because of an oval-shaped mass (13 cm × 8.7 cm) located in the mid-abdomen. An enlarged tubular-shaped structure that had the opacity of soft tissue located in dorsal to the bladder to the middle of the abdomen, and an oval-shaped mass (5.28 cm × 3.26 cm), which was suspected to be a medial iliac lymph node located at the sixth to seventh lumbar level. Abdominal ultrasonography revealed gas and fluid in the lumen of the uterine horn with a severely thickened wall, round enlarged lymph nodes around the genitourinary system, and free fluid in the abdominal cavity. Based on these results, pyometra was suspected, and an exploratory laparotomy was performed for ovariohysterectomy. The resected ovary and uterus were macroscopically hypertrophied. Histopathological examination of the ovary and uterus revealed neoplastic proliferation of large round cells with strong immunoreactivity for CD3, indicating T-cell lymphoma. Therefore, the young dog was diagnosed with genital lymphoma. CONCLUSIONS: The present report describes T-cell lymphoma infiltrating the uterus and ovaries in a young dog, which is rarely diagnosed and could aid in the differential diagnosis of genital diseases in young dogs.

Improvement of the intestinal epithelial barrier during laxative effects of phlorotannin in loperamide-induced constipation of SD rats.

BACKGROUND: Disruptions of the intestinal epithelial barrier (IEB) are frequently observed in various digestive diseases, including irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD). This study assessed the improvement in the IEB during the laxative activity of phlorotannin (Pt) harvested from Ecklonia cava in constipation by examining the changes in the expression of the regulatory proteins for the tight junction (TJ) and adherens junction (AJ), and inflammatory cytokines in Sprague Dawley (SD) rats with loperamide (Lm)-induced constipation after a Pt treatment. RESULTS: The Pt treatment induced laxative activity, including the improvement of feces-related parameters, gastrointestinal transit rate, and histological structure of the mid colon in Lm-treated SD rats. In addition, significant recovery effects were detected in the histology of IEB, including the mucus layer, epithelial cells, and lamina propria in the mid colon of Lm + Pt treated SD rats. The expression levels of E-cadherin and p120-catenin for AJ and the ZO-1, occludin, and Claudin-1 genes for TJ in epithelial cells were improved remarkably after the Pt treatment, but the rate of increase was different. Furthermore, the Pt treatment increased the expression level of several inflammatory cytokines, such as TNF-α, IL-6, IL-1ß, IL-13, and IL-4 in Lm + Pt treated SD rats. CONCLUSIONS: These results provide the first evidence that the laxative activity of Pt in SD rats with Lm-induced constipation phenotypes involve improvements in the IEB.

Secondary Organic Aerosol Mass Yields from NO3 Oxidation of α-Pinene and Δ-Carene: Effect of RO2 Radical Fate.

Dark chamber experiments were conducted to study the SOA formed from the oxidation of α-pinene and Δ-carene under different peroxy radical (RO2) fate regimes: RO2 + NO3, RO2 + RO2, and RO2 + HO2. SOA mass yields from α-pinene oxidation were <1 to ∼25% and strongly dependent on available OA mass up to ∼100 µg m-3. The strong yield dependence of α-pinene oxidation is driven by absorptive partitioning to OA and not by available surface area for condensation. Yields from Δ-carene + NO3 were consistently higher, ranging from ∼10-50% with some dependence on OA for <25 µg m-3. Explicit kinetic modeling including vapor wall losses was conducted to enable comparisons across VOC precursors and RO2 fate regimes and to determine atmospherically relevant yields. Furthermore, SOA yields were similar for each monoterpene across the nominal RO2 + NO3, RO2 + RO2, or RO2 + HO2 regimes; thus, the volatility basis sets (VBS) constructed were independent of the chemical regime. Elemental O/C ratios of ∼0.4-0.6 and nitrate/organic mass ratios of ∼0.15 were observed in the particle phase for both monoterpenes in all regimes, using aerosol mass spectrometer (AMS) measurements. An empirical relationship for estimating particle density using AMS-derived elemental ratios, previously reported in the literature for non-nitrate containing OA, was successfully adapted to organic nitrate-rich SOA. Observations from an NO3- chemical ionization mass spectrometer (NO3-CIMS) suggest that Δ-carene more readily forms low-volatility gas-phase highly oxygenated molecules (HOMs) than α-pinene, which primarily forms volatile and semivolatile species, when reacted with NO3, regardless of RO2 regime. The similar Δ-carene SOA yields across regimes, high O/C ratios, and presence of HOMs, suggest that unimolecular and multistep processes such as alkoxy radical isomerization and decomposition may play a role in the formation of SOA from Δ-carene + NO3. The scarcity of peroxide functional groups (on average, 14% of C10 groups carried a peroxide functional group in one test experiment in the RO2 + RO2 regime) appears to rule out a major role for autoxidation and organic peroxide (ROOH, ROOR) formation. The consistently substantially lower SOA yields observed for α-pinene + NO3 suggest such pathways are less available for this precursor. The marked and robust regime-independent difference in SOA yield from two different precursor monoterpenes suggests that in order to accurately model SOA production in forested regions the chemical mechanism must feature some distinction among different monoterpenes.

Factors affecting reproductive outcomes in lactating dairy cows that undergo presynchronization-Ovsynch and successive resynchronization programs.

This study was designed to identify the factors affecting reproductive outcomes in lactating dairy cows undergoing Presynchronization-Ovsynch and successive resynchronization programs. Data were collected from 1,458 cows on 11 dairy farms, regarding nutrition, health, reproduction, and specifically reproductive programs used for the first timed artificial insemination (TAI; Modified Presynch-Ovsynch or Modified Double-Ovsynch) and for re-inseminations (Ovsynch or PreGnRH-Ovsynch); as well as the weather. Body condition score (BCS) and timing of TAI affected (P < 0.01) the probability of pregnancy per AI after first TAI. Cows with a BCS ≥3.25 were more likely (P < 0.01) to be pregnant at 31 (odds ratio [OR]: 1.85) and 49 (OR: 1.93) days after the first TAI than cows with BCS ≤2.75. Cows inseminated during months of heat stress (June to September) were less likely (P < 0.01) to be pregnant at 31 (OR: 0.74) and 49 (OR: 0.68) days after first TAI than those inseminated during months of no heat stress (October to May). Cows that had a pre- or postpartum disorder were more likely to lose their pregnancy (OR: 2.17, P < 0.01) than those that did not. Cows inseminated ≥76 days after calving (OR: 1.67, P < 0.1) or during the months of heat stress (OR: 2.02, P < 0.05) were also more likely to lose pregnancy than cows inseminated ≤75 days after calving or during the months of no heat stress. Following successive resynchronizations, cows with a third (OR: 1.32, P < 0.1) or fourth (OR: 1.68, P < 0.05) TAI were more likely to be pregnant than those with a second TAI. Cows with BCS ≥3.25 at the beginning of resynchronization were more likely (OR: 1.49, P < 0.05) to be pregnant than cows with BCS ≤2.75. Finally, the likelihood of being pregnant by 210 days postpartum was positively associated with a favorable BCS, but negatively associated with the presence of a pre- or postpartum disorder and a larger number of days to first TAI following calving (≥76 vs. ≤75 days). In conclusion, high BCS has beneficial effects during the entire reproductive period, whereas TAI during heat stress, the presence of a pre- or postpartum disorder, a larger number of days to first TAI following calving, and TAI number (second or ≥ fifth) adversely affects the outcomes associated with pregnancy during the early or later breeding periods in lactating dairy cows undergoing Presynchronization-Ovsynch and successive resynchronization programs.

Volatility of Springtime ambient organic aerosol derived with thermodenuder aerosol mass spectrometry in Seoul, Korea.

The volatilities of ambient organic aerosol (OA) components are important to forecasting OA formation with models. However, providing the OA volatility distribution inputs for models is challenging, and models often rely on measurements from chamber experiments. We measured the volatility of submicron ambient OA in Seoul during May/June of 2019 by connecting a thermodenuder to an Aerodyne Time-of-Flight Aerosol Mass Spectrometer (AMS). We calculated a volatility basis set (VBS) of the organic aerosol with a thermodenuder mass transfer model and data from the thermodenuder set to various temperatures (30-200 °C). We found a large discrepancy between the measured ambient VBS and a reference VBS used in air quality models, with the ambient organics being less volatile. The results suggest that a modeling study that tries to account for this discrepancy may be needed to identify the impact it has on modeling outcomes. Chamber experiments aiming to determine VBSs for specific chemical systems should address limitations caused by wall losses and incomplete modeling parameters.

Evaluation of Dose-Dependent Obesity and Diabetes-Related Complications of Water Chestnut (Fruit of Trapa japonica) Extracts in Type II Obese Diabetic Mice Induced by 45% Kcal High-Fat Diet.

Background and Objectives: The currently used pharmacological agents for metabolic disorders such as type II diabetes have several limitations and adverse effects; thus, there is a need for alternative therapeutic drugs and health functional foods. Materials and Methods: This study investigated the pharmacological effects of water chestnut (fruit of Trapa japonica) extracts (WC: 50-200 mg/kg) for type II diabetes using a 45% Kcal high-fat diet (HFD)-fed type II obese diabetic mice model for a period of 84 days, and the effects were compared to those of metformin (250 mg/kg). Results: Increases in body weight, serum biochemical indices such as triglycerides, low-density lipoprotein, and blood urea nitrogen, increases in antioxidant defense system enzymes such as catalase, superoxide dismutase, and glutathione, and mRNA expressions (such as AMPKα1 and AMPKα2) in the liver tissue and mRNA expressions (such as AMPKα2 mRNA, leptin, and C/EBPα) in the adipose tissue were observed in the HFD control group. The WC (50 mg/kg)-administered group showed no significant improvements in diabetic complications. However, HFD-induced obesity and diabetes-related complications such as hyperlipidemia, diabetic nephropathy, nonalcoholic fatty liver disease (NAFLD), oxidative stress, activity of antioxidant defense systems, and gene expressions were significantly and dose-dependently inhibited and/or normalized by oral administration of WC (100 mg/kg and 200 mg/kg), particularly at a dose of 100 mg/kg. Conclusions: The results of this study suggest that WC at an appropriate dose could be used to develop an effective therapeutic drug or functional food for type II diabetes and various associated complications, including NAFLD.

Selective use of a modified pre-synchronization-Ovsynch and resynchronization reproductive strategy in dairy herds: A field application study.

We aimed to evaluate whether a modified pre-synchronization-Ovsynch (MPO) and resynchronization method, adjusted for the timing of biweekly reproductive consulting visits, could be implemented successfully under field conditions in dairy herds. Forty-five days after calving (calving: Day 0), 1,182 cows were assigned randomly to Ovsynch, MPO or control groups. (1) Cows were administered GnRH on Day 65, PGF2α on Day 72 and GnRH 56 hr later, followed by timed artificial insemination (TAI) 16 hr later (Ovsynch, n = 380). (2) Cows with a CL were administered PGF2α (n = 204) and cows without were administered GnRH (n = 199) on Day 45. Then, each cow was administered PGF2α on Day 55 (9 to 12 days later), GnRH on Day 58 and underwent Ovsynch 7 days later (selective MPO [sMPO] n = 403). (3) The remaining cows underwent AI when oestrus was detected (EDAI, n = 399). The probabilities of pregnancy per AI 30 and 45 days after the first AI were higher in the sMPO group (odds ratios 1.99 and 1.92, p < .0001) than in the EDAI group. In addition, the probability of pregnancy by 105 days postpartum tended to be higher (p < .1) in the sMPO group than in the EDAI and Ovsynch groups, which shortened the mean interval from calving to pregnancy in the sMPO group (3.4 and 4.2 days, respectively) than in the EDAI and Ovsynch groups. In the sMPO group, the interval between the first and second treatments during pre-synchronization did not affect the probability of pregnancy per AI after the first AI. The probability of pregnancy per AI after the second AI did not differ between the Ovsynch, sMPO and EDAI groups. In conclusion, the sMPO programme, adjusted for the timing of biweekly reproductive consulting visits, followed by resynchronization, could be successfully adopted in field conditions, and is associated with good reproductive performance in dairy herds.

Comparison of cisplatin-induced anti-tumor response in CT26 syngeneic tumors of three BALB/c substrains.

BACKGROUND: To determine whether the background of BALB/c substrains affects the response to anti-tumor drugs, we measured for alterations in tumor growth, histopathological structure of the tumor, and expressions of tumor-related proteins in three BALB/c substrains derived from different sources (BALB/cKorl, BALB/cA and BALB/cB), after exposure to varying concentrations of cisplatin (0.1, 1 and 5 mg/kg). RESULTS: Cisplatin treatment induced similar responses for body and organ weights, serum analyzing factors, and blood analyzing factors in all BALB/c substrains with CT26 syngeneic tumor. Few differences were detected in the volume and histopathological structure of the CT26 tumor. Growth inhibition of CT26 tumors after exposure to cisplatin was greater in the BALB/cB substrain than BALB/cKorl and BALB/cA substrains, and a similar pattern was observed in the histopathological structure of tumors. However, the expression levels of other tumor-related factors, including Ki67, p27, p53, Bcl-2-associated X protein (Bax), B-cell lymphoma 2 (Bcl-2), caspase-3 (Cas-3), matrix metallopeptidase 2 (MMP2) and vascular endothelial growth factor (VEGF) proteins, were constantly maintained in the tumors of all three substrains after cisplatin treatment. A similar decrease pattern was observed for the expressions of inflammatory cytokines, including interleukin (IL)-1ß, IL-6 and IL-10, in the CT26 tumors of the three BALB/c substrains. CONCLUSIONS: Taken together, results of the present study indicate that the genetic background of the three BALB/c substrains has no major effect on the therapeutic responsiveness of cisplatin, except growth and histopathology of the CT26 syngeneic tumor.

Lateral Flank Approach for Ovariohysterectomy in a Lion (Panthera leo) with a Ruptured Pyometra.

An 8.5-year-old intact female lion (Panthera leo) with a history of vomiting, lethargy, and anorexia was referred to our institution. On physical examination, the lion weighed 180 kg and had a rectal temperature of 40 °C. Blood analysis showed mild neutrophilic leukocytosis, and abdominal ultrasonography revealed an enlarged uterus with echogenic fluid. Based on the clinical signs and hematologic and ultrasonographic findings, the lion was tentatively diagnosed with pyometra. Ovariohysterectomy was performed using the lateral flank approach to avoid complications that can occur with ventral celiotomy. Surgery was performed successfully despite unexpected rupture of the uterus which had occurred before the surgery. The lion recovered uneventfully and continued to do well at the 1 year follow up after surgery. To the best of our knowledge, this is the first reported case of ovariohysterectomy with the lateral flank approach in a lion with pyometra. Our report suggests that ovariohysterectomy with the lateral flank approach could be considered as an alternative method for pyometra in wild big cats with risk of complications at the surgical site.

Anti-inflammatory effects of Capparis ecuadorica extract in phthalic-anhydride-induced atopic dermatitis of IL-4/Luc/CNS-1 transgenic mice.

CONTEXT: The natural products derived from Capparis ecuadorica H.H. Iltis (Capparaceae) could have great potential for anti-inflammation since they inhibited the inflammatory response in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. OBJECT: This study investigated the anti-inflammatory effects and related mechanism of methanol extract of C. ecuadorica leaves (MCE) during atopic dermatitis (AD) responses. MATERIALS AND METHODS: Alterations in the phenotypical markers for AD, luciferase signal, iNOS-mediated COX-2 induction pathway, and inflammasome activation were analysed in non-Tg (n = 5) and 15% phthalic anhydride (PA) treated IL-4/Luc/CNS-1 transgenic (Tg) HR1 mice (n = 5 per group), subsequent to treatment with acetone-olive oil (AOO), vehicle (DMSO) and two dose MCE (20 and 40 mg/kg) three times a week for 4 weeks. RESULTS: MCE treatment reduced the intracellular ROS level (48.2%), NO concentration (7.1 mmol/L) and inflammatory cytokine expressions (39.1%) in the LPS-stimulated RAW264.7 cells. A significant decrease was detected for ear thickness (16.9%), weight of lymph node (0.7 mg), IgE concentration (1.9 µg/mL), and epidermal thickness (31.8%) of the PA + MCE treated Tg mice. MCE treatment induced the decrease of luciferase signal derived from the IL-4 promoter and the recovery of the IL-4 downstream regulator cytokines. PA + MCE treated Tg mice showed decreasing infiltration of mast cells (42.5%), iNOS-mediated COX-2 induction pathway, MAPK signalling pathway and inflammasome activation in the ear tissue. CONCLUSIONS: These findings provide the first evidence that MCE may have great potential to suppress chemical-induced skin inflammation through the suppression of IL-4 cytokine and the iNOS-mediated COX-2 induction pathway, and activation of inflammasome.

Reproductive performance following a modified Presynch-Ovsynch, Double-Ovsynch, or conventional reproductive management program in Korean dairy herds.

We aimed to compare the reproductive performance of dairy cattle following a modified Presynch-Ovsynch, Double-Ovsynch, or conventional reproductive management program (CRMP). On Day 30 (±5) after calving (calving = Day 0), 960 lactating cows were assigned randomly to one of two presynchronization treatments, before the synchronization of ovulation (Ovsynch) or CRMP without presynchronization. Cows were administered prostaglandin F2α (PGF2α) on Days 38 (±5) and 52, and gonadotropin-releasing hormone (GnRH) on Day 55 (Presynch-G-Ovsynch group, n = 333); or GnRH on Day 45 (±5), PGF2α on Day 52, and GnRH again on Day 55 (Double-Ovsynch group, n = 307). Thereafter, each cow underwent Ovsynch 7 days later: GnRH on Day 62, PGF2α on Day 69, and GnRH again 56 h later, followed by timed artificial insemination (AI) 16 h later. The remaining cows underwent AI when estrus was detected or Ovsynch (CRMP group, n = 320). In a subset of cows (each n = 40) in the two presynchronization groups, blood collections and ovarian ultrasonography were performed on Days 30 (±4), 52, 62, and 69, and uterine cytology on Days 30 (±4) and 52. The probabilities of pregnancy per AI 32 and 60 days after the first AI were higher in the Presynch-G-Ovsynch (odds ratio [OR]: 1.89 and 1.81, P < 0.01) and Double-Ovsynch (OR: 1.63 and 1.60, P < 0.05) groups than in the CRMP group. The likelihood of pregnancy by 210 days postpartum was higher (P < 0.05) in Presynch-G-Ovsynch (hazard ratio [HR]: 1.29) and Double-Ovsynch (HR: 1.31) groups than in the CRMP group, whereas the least square mean number of inseminations per conception was lower (P < 0.05) in Presynch-G-Ovsynch (1.8) and Double-Ovsynch (1.8) groups than in the CRMP group (2.1). The percentages of cows with serum progesterone concentrations ≥1.0 ng/mL or with a corpus luteum (CL) did not differ between the groups (P > 0.1) on Days 30, 62, and 69, but were lower (P < 0.05) on Day 52 in the Presynch-G-Ovsynch than in the Double-Ovsynch groups. However, the diameter of the dominant follicles, the proportion of neutrophils in uterine cytological samples, and the prevalence of an accessory CL on Day 69 did not differ (P > 0.1) between the two groups. In conclusion, both the Presynch-G-Ovsynch and Double-Ovsynch programs improved reproductive performance vs. CRMP in smallholder Korean dairy herds, and there were no differences in the ovarian endocrine and structural dynamics, or uterine health, between the two programs involving presynchronization.

Effect of Minoxidil on Trabecular Outflow via the Paracellular Pathway.

PURPOSE: To investigate the pathway and effects of minoxidil on trabecular outflow in cultured human trabecular meshwork (TM) cells. METHODS: After exposing primarily cultured TM cells to 0, 10, 50, or 100 µM minoxidil sulfate (MS), trabecular outflow was assessed by measuring TM cell monolayer permeability to carboxyfluorescein and transepithelial electrical resistance. To assess the pathway of permeability changes, caveolin-1, occludin, and claudin-5 levels were measured via western blot. Generation of reactive oxygen species (ROS) was measured using the dichlorofluorescein diacetate assay. To assess the involvement of nitric oxide (NO) in minoxidil-induced permeability increase, the degrees of endothelial nitric oxide synthase mRNA expression and NO production were measured with reverse transcription polymerase chain reaction and Griess assays, respectively. Permeability was also measured with co-exposure to 50 µM N-acetyl cysteine. RESULTS: MS significantly increased TM cell monolayer permeability (p < 0.05) and decreased transepithelial electrical resistance (p < 0.05). MS decreased the degree of endothelial nitric oxide synthase mRNA expression but did not affect NO production. MS decreased occludin and claudin-5 levels but did not affect caveolin-1 level. MS at 100 µM increased the generation of ROS, and MS-induced permeability increase was attenuated after co-exposure to 50 µM N-acetyl cysteine. CONCLUSIONS: Minoxidil may preferentially increase trabecular permeability via a paracellular pathway by downregulation of tight junction proteins. This minoxidil-induced permeability through the TM may be mediated by generation of ROS.

Therapeutic effects of a liquid bandage prepared with cellulose powders from Styela clava tunics and Broussonetia kazinoki bark: Healing of surgical wounds on the skin of Sprague Dawley rats.

Cellulose in different forms has extensively been applied in biomedical treatments, including scaffolding, tissue engineering and tissue formation. To evaluate the therapeutic effects of a liquid bandage (LB) prepared with cellulose powders from Styela clava tunics (SCT) and Broussonetia kazinoki bark (BSLB) for healing cutaneous wounds, the remedial effects of a low concentration (LoBSLB) and a high concentration (HiBSLB) of BSLB on skin regeneration and toxicity in Sprague Dawley rats. Results indicated that the total area of skin involved in the surgical wound was lower in the BSLB­treated group compared with the Vehicle­treated group at days 4­12, although some variations were observed in the HiBSLB­treated group. In addition, the BSLB­treated group showed significantly enhanced width of the re­epithelialization region and epidermal thickness when compared with the Vehicle­treated group. Furthermore, significant stimulation in the expression level of collagen­1 and the signaling pathway of VEGF after topical application of BSLB was indicated. No liver or kidney toxicities were detected for either doses of BSLB. Overall, the results of the present study suggest that BSLB accelerates the process of wound healing in surgical skin wounds of Sprague Dawley rats through stimulation of re­epithelialization and connective tissue formation, without any accompanying significant toxicity.

Metabolomics approach to serum biomarker for laxative effects of red Liriope platyphylla in loperamide-induced constipation of SD rats.

Red Liriope platyphylla (RLP) is a known herbal medicine used in the treatment of some chronic diseases including constipation, neurodegenerative disorders, diabetes and obesity. To determine and characterize putative biomarkers that predict the laxative effects induced by RLP treatment, alteration of endogenous metabolites was measured in the serum of loperamide (Lop)-induced constipation rats after administration of RLP extract (EtRLP) using 1H nuclear magnetic resonance (1H NMR) spectral data. The urine volume and amounts, and weights and water contents of stools were significantly recovered in the Lop + EtRLP treated group as compared to the No group, whereas body weight and food intake maintained constant levels. Also, significant recoveries in the thickness of mucosa and muscle were detected in the colon of the Lop + EtRLP treated group. Furthermore, pattern recognition showed absolutely different clustering of the serum analysis parameters when comparing the Lop treated group and Lop + EtRLP treated group. Of the 33 endogenous metabolites, 7 amino acids (alanine, arginine, glutamate, glutamine, glycine, threonine and valine) and 8 endogenous metabolites (betaine, creatine, glucose, taurine, ethanol, lactate, glycerol and succinate) were dramatically increased in the Lop + EtRLP treated SD rats. These results provide the first evidence pertaining to metabolic changes in the constipation rats treated with Lop + EtRLP. Additionally, these findings correlate with changes observed in 15 metabolites during the laxative effects of EtRLP.

Heat Shock Factor 1 Predicts Poor Prognosis of Gastric Cancer.

PURPOSE: Heat shock factor 1 (HSF1) is a key regulator of the heat shock response and plays an important role in various cancers. However, the role of HSF1 in gastric cancer is still unknown. The present study evaluated the function of HSF1 and related mechanisms in gastric cancer. MATERIALS AND METHODS: The expression levels of HSF1 in normal and gastric cancer tissues were compared using cDNA microarray data from the NCBI Gene Expression Omnibus (GEO) dataset. The proliferation of gastric cancer cells was analyzed using the WST assay. Transwell migration and invasion assays were used to evaluate the migration and invasion abilities of gastric cancer cells. Protein levels of HSF1 were analyzed using immunohistochemical staining of tissue microarrays from patients with gastric cancer. RESULTS: HSF1 expression was significantly higher in gastric cancer tissue than in normal tissue. Knockdown of HSF1 reduced the proliferation, migration, and invasion of gastric cancer cells, while HSF1 overexpression promoted proliferation, migration, and invasion of gastric cancer cells. Furthermore, HSF1 promoted the proliferation of gastric cancer cells in vivo. In Kaplan-Meier analysis, high levels of HSF1 were associated with poor prognosis for patients with gastric cancer (p=0.028). CONCLUSION: HSF1 may be closely associated with the proliferation and motility of gastric cancer cells and poor prognosis of patients with gastric cancer. Accordingly, HSF1 could serve as a prognostic marker for gastric cancer.

Associations between serum calcium concentration and postpartum health and reproductive performance in dairy cows.

In the present study, the aim was to evaluate the associations between serum calcium concentration after calving and serum metabolites, postpartum disorders, and reproductive performance in dairy cows. Blood samples were collected from 200 Holstein cows immediately and 1, 2, 4, 6, and 8 weeks after calving to measure serum metabolites and progesterone concentrations. Cows were divided into three groups on the basis of the mean serum calcium concentration after calving: a Low group (<7.9 mg/dL, n = 52), a Moderate group (7.9-9.6 mg/dL, n = 100), and a High group (≥9.7 mg/dL, n = 48). Total cholesterol (TCH) concentration was greater in the High group than in the Moderate group during the postpartum period (P < 0.01). The High group had greater albumin concentrations during the postpartum period (P < 0.01) and glucose concentrations after calving and 1 week postpartum (P < 0.05) than the Low and Moderate groups. The High group had a lesser incidence of retained placenta than the Low (P < 0.1) and Moderate (P < 0.01) groups, and a lesser incidence of clinical endometritis than the Moderate group (P < 0.05). The probability of resuming estrous cyclicity by 8 weeks postpartum was greater in the High group than in the Low group (hazard ratio = 3.71, P < 0.05). In conclusion, greater serum calcium concentration after calving is associated with greater serum TCH, albumin, and glucose concentrations, a lesser incidence of retained placenta, and clinical endometritis, and earlier resumption of estrous cyclicity in dairy cows.

Berberine Suppresses Fibronectin Expression through Inhibition of c-Jun Phosphorylation in Breast Cancer Cells.

PURPOSE: The exact mechanism regulating fibronectin (FN) expression in breast cancer cells has not been fully elucidated. In this study, we investigated the pharmacological mechanism of berberine (BBR) with respect to FN expression in triple-negative breast cancer (TNBC) cells. METHODS: The clinical significance of FN mRNA expression was analyzed using the Kaplan-Meier plotter database (http://kmplot.com/breast). FN mRNA and protein expression levels were analyzed by real-time polymerase chain reaction and western blotting, respectively. RESULTS: Using publicly available clinical data, we observed that high FN expression was associated with poor prognosis in patients with breast cancer. FN mRNA and protein expression was increased in TNBC cells compared with non-TNBC cells. As expected, recombinant human FN significantly induced cell spreading and adhesion in MDA-MB231 TNBC cells. We also investigated the regulatory mechanism underlying FN expression. Basal levels of FN mRNA and protein expression were downregulated by a specific activator protein-1 (AP-1) inhibitor, SR11302. Interestingly, FN expression in TNBC cells was dose-dependently decreased by BBR treatment. The level of c-Jun phosphorylation was also decreased by BBR treatment. CONCLUSION: Our findings demonstrate that FN expression is regulated via an AP-1-dependent mechanism, and that BBR suppresses FN expression in TNBC cells through inhibition of AP-1 activity.

Hypercapnia does not shorten emergence time from propofol anesthesia: a pilot randomized clinical study.

BACKGROUND: The elimination of anesthetic agents is a decisive factor in the emergence from general anesthesia. In this pilot study, we hypothesized that hypercapnia would decrease the emergence time from propofol anesthesia by increasing cardiac output and cerebral blood flow. METHODS: A total of 32 patients were randomly divided into two groups based on the end-tidal carbon dioxide values: 30 mmHg (the hypocapnia group) and 50 mmHg (the hypercapnia group). Propofol and remifentanil were infused to maintain a bispectral index of 40-50. Remifentanil infusion was stopped 10 min before the discontinuation of propofol. After cessation of propofol infusion, ventilation settings in the hypocapnia group were maintained constant; a rebreathing tube was connected to the respiratory circuit in the hypercapnia group. The time to spontaneous respiration, eye opening (primary endpoint), mouth opening, and tracheal extubation was recorded and analyzed. RESULTS: Time to eye opening was 9.7 (1.3) min in the hypocapnia group and 9.0 (1.0) min in the hypercapnia group. The difference in the mean times to eye opening between groups was -0.7 min (95% CI, -4.0 to 2.7, P = 0.688). On multiple regression analysis, there was a significant difference in the mean time to eye opening between males and females. Females recovered about 3.6 min faster than males (95% CI, -6.1 to -1.1, P = 0.009). CONCLUSIONS: We could not detect a beneficial effect of hypercapnia on propofol emergence time. Irrespective of hypercapnia, females seemed to recover faster than males.

Detailed Anatomy of Osteoperiosteal Ligamentous Structures in the Forehead.

This study aimed to present the anatomic characteristics of osteoperiosteal ligamentous attachments of the forehead and provide a better understanding of lateral eyebrow descent for safe and effective foreheadplasty. Anatomic dissections of the face were performed in 10 fresh Korean adult cadavers (20 hemifaces) using 2.5× magnification surgical loupes. Supraorbital, inferomedial orbital, and frontonasal osteoperiosteal ligamentous attachments were identified as fibrous tissues originating from a bone, and their tensile strengths were measured. The supraorbital osteoperiosteal ligamentous attachment had medial and lateral parts. It can be classified into 4 subtypes. It was located 11.0 ±â€Š6.6 mm lateral to the midline and 9.2 ±â€Š12.3 mm superior to the superior orbital margin. The inferomedial orbital osteoperiosteal ligamentous attachment was located 16.2 ±â€Š3.9 mm lateral to the midline and 2.2 ±â€Š2.7 mm inferior to the superior orbital margin, whereas the frontonasal osteoperiosteal ligamentous attachment was located 5.4 ±â€Š2.3 mm lateral to the midline and 1.4 ±â€Š8.5 mm superior to the superior orbital margin. Tensile strengths of all the osteoperiosteal ligamentous attachments in the forehead were above 10 N. These results indicate that osteoperiosteal ligamentous attachments develop in the rather medial region of the eyebrow and have a tensile strength adequate enough to maintain the medial eyebrow. Thus, the current study provides surgeons with detailed anatomic information that can be used as a valuable reference for forehead rejuvenation procedures.