Previous studies support the important role of vascular endothelial growth factor (VEGF) and syndecan-4 in the pathogenesis of osteoarthritis (OA). Both VEGF and syndecan-4 are expressed by ...chondrocytes and both are involved in the regulation of matrix metalloproteinase-3, resulting in the activation of aggrecanase II (ADAMTS-5), which is essential in the pathogenesis of OA. However, the relationship between VEGF and syndecan-4 has not been established. As a pilot study, we assayed the expression of VEGF and syndecan-4 in cartilage samples and cultured chondrocytes from osteoarthritic knee joints and analysed the relationship between these two factors. Specimens were collected from 21 female patients (29 knees) who underwent total knee replacement due to severe medial OA of the knee (Kellgren-Lawrence grade 4). Articular cartilage samples, obtained from bone and cartilage excised during surgery, were analysed and used for chondrocyte culture. We found that the levels of expression of VEGF and syndecan-4 mRNA did not differ significantly between medial femoral cartilage with severe degenerative changes and lateral femoral cartilage that appeared grossly normal (p = 0.443 and 0.622, respectively). Likewise, the levels of expression of VEGF and syndecan-4 mRNA were similar in cultured chondrocytes from medial and lateral femoral cartilage. The levels of expression of VEGF and syndecan-4 mRNAs were significantly and positively correlated in cartilage explant (r = 0.601, p = 0.003) but not in cultured chondrocytes. These results suggest that there is a close relationship between VEGF and syndecan-4 in the cartilage of patients with OA. Further studies are needed to determine the exact pathway by which these two factors interact in the pathogenesis of OA.
Apoptosis signal-regulating kinase 1 (ASK1) is a mitogen-activated protein kinase kinase kinase that can activate the c-Jun N-terminal kinase and the p38 signaling pathways. It plays a critical role ...in cytokine- and stress-induced apoptosis. To further characterize the mechanism of the regulation of the ASK1 signal, we searched for ASK1-interacting proteins employing the yeast two-hybrid method. The yeast two-hybrid assay indicated that mouse glutathione S-transferase Mu 1-1 (mGSTM1-1), an enzyme involved in the metabolism of drugs and xenobiotics, interacted with ASK1. We subsequently confirmed that mGSTM1-1 physically associated with ASK1 both in vivo and in vitro. The in vitro binding assay indicated that the C-terminal portion of mGSTM1-1 and the N-terminal region of ASK1 were crucial for binding one another. Furthermore, mGSTM1-1 suppressed stress-stimulated ASK1 activity in cultured cells. mGSTM1-1 also blocked ASK1 oligomerization. The ASK1 inhibition by mGSTM1-1 occurred independently of the glutathione-conjugating activity of mGSTM1-1. Moreover, mGSTM1-1 repressed ASK1-dependent apoptotic cell death. Taken together, our findings suggest that mGSTM1-1 functions as an endogenous inhibitor of ASK1. This highlights a novel function for mGSTM1-1 insofar as mGSTM1-1 may modulate stress-mediated signals by repressing ASK1, and this activity occurs independently of its well-known catalytic activity in intracellular glutathione metabolism.
Through metabolic engineering, scientists seek to modify the metabolic pathways of living organisms to facilitate optimized, efficient production of target biomolecules. During the past decade, we ...have seen notable improvements in biotechnology, many of which have been based on metabolically engineered microorganisms. Recent developments in the fields of functional genomics, transcriptomics, proteomics, and metabolomics have changed metabolic engineering strategies from the local pathway level to the whole system level. This article focuses on recent advances in the field of metabolic engineering, which have been powered by the combined approaches of the various “omics” that allow us to understand the microbial metabolism at a global scale and to develop more effectively redesigned metabolic pathways for the enhanced production of target bioproducts.
Aims: To evaluate an integrated cell culture (ICC)–multiplex‐nested PCR using the buffalo green monkey kidney (BGMK) cells for the simultaneous detection of both enteroviruses and adenoviruses in ...surface water and tap water samples and optimize the procedure for more sensitive detection of virus showing no apparent cytopathic effect (CPE).
Methods and Results: A total of 69 surface water and 50 tap water samples were analysed by the ICC–multiplex‐nested PCR. All the PCRs were performed five times with a cell lysate from each flask after at least 2 weeks incubation. Forty‐six surface water samples (66·7%) and 23 tap water samples (46·0%) exhibited CPE by the cell culture method. By using an ICC–multiplex‐nested PCR, 53 surface water samples (76·8%) and 29 tap water samples (58·0%) were determined as containing infectious enteric viral particles.
Conclusions: An ICC–PCR method with a long incubation time using BGMK cells enables the simultaneous detection of enteroviruses and adenoviruses from environmental water samples, including tap water, even with low numbers of viruses.
Significance and Impact of the Study: A method capable of detecting small numbers of viral particles is necessary.
This study was performed to investigate the effects of the combined treatment of high pressure and heat on the quality of carrot juice, and to optimize the process condition. About 95% of food ...quality‐related enzymes were lost at 400 MPa and 70 °C, for 10 min, while α‐ and β‐carotene were relatively stable at the combined process. The optimum process condition was estimated at 395 to 445 MPa, 70 °C, for 8 to 11 min. These results indicate that the combined treatment of high pressure and mild heat could be used as an effective process for production of high‐quality carrot juice.
Background
Although laparoscopic surgery significantly reduces surgical trauma compared to open surgery, postoperative ileus is a frequent and significant complication after abdominal surgery. Unlike ...laparoscopic colorectal surgery, the effects of epidural analgesia on postoperative recovery after laparoscopic gastrectomy are not well established. We compared the effects of epidural analgesia to those of conventional intravenous (IV) analgesia on the recovery of bowel function after laparoscopic gastrectomy.
Method
Eighty-six patients undergoing laparoscopic gastrectomy randomly received either patient-controlled epidural analgesia with ropivacaine and fentanyl (Epi PCA group) or patient-controlled IV analgesia with fentanyl (IV PCA group), beginning immediately before incision and continuing for 48 h thereafter. The primary endpoint was recovery of bowel function, evaluated by the time to first flatus. The balance of the autonomic nervous system, pain scores, duration of postoperative hospital stay, and complications were assessed.
Results
The time to first flatus was shorter in the epidural PCA group compared with the IV PCA group (61.3 ± 11.1 vs. 70.0 ± 12.3 h,
P
= 0.001). Low-frequency/high-frequency power ratios during surgery were significantly higher in the IV PCA group, compared with baseline and those in the epidural PCA group. The epidural PCA group had lower pain scores during the first 1 h postoperatively and required less analgesics during the first 6 h postoperatively.
Conclusions
Compared with IV PCA, epidural PCA facilitated postoperative recovery of bowel function after laparoscopic gastrectomy without increasing the length of hospital stay or PCA-related complications. This beneficial effect of epidural analgesia might be attributed to attenuation of sympathetic hyperactivation, improved analgesia, and reduced opioid use.
Objective
K. K. and S.-K. C. are co-first authors, and C. K. and S.-C. B. are co-senior authors.Two transcription factors in the type I interferon pathway, IRF5 and STAT4, have been genetically ...associated with susceptibility to both systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). This study aimed to determine whether these two genes interact with each other to affect the disease susceptibilities.
Methods
The genetic interactions between IRF5 and STAT4 polymorphisms in SLE and RA susceptibility were examined using the epistasis options in PLINK software. This study analyzes the genetic data from 2558 unrelated Korean participants including 589 SLE patients, 987 RA patients, and 982 controls.
Results
All 12 polymorphisms were individually associated with SLE susceptibility (p = 2.49 × 10−8 to 0.00360). Among the three SLE-associated polymorphisms of IRF5, rs77571059, alternatively called CGGGG(3–4) indel, exhibited the lowest p value (4.60 × 10−5) and accounted for the observed associations of the other two single-nucleotide polymorphisms (SNPs). Among the nine SLE-associated SNPs of STAT4, rs16833215 exhibited the lowest p value (2.49 × 10−8) and accounted for all the other associations. These two polymorphisms, rs77571059 of IRF5 and rs16833215 of STAT4, interacted with each other for SLE susceptibility in a redundant manner (ORinteraction = 0.77, Pepistasis = 0.040). Furthermore, these two polymorphisms, which had been individually associated with RA susceptibility, also interacted for RA susceptibility in the same manner (ORinteraction = 0.75, Pepistasis = 0.014).
Conclusions
A redundant interaction between IRF5 and STAT4 polymorphisms was found in susceptibility to the type I interferon pathway-associated rheumatic autoimmune diseases, SLE and RA, calling for further studies on confirmation of these findings.
Objective: To evaluate the effects of low-intensity ultrasound (LIUS) stimulation on the anabolic state of human cartilage from patients with osteoarthritis (OA).
Methods: Explant cultures of human ...OA cartilage were stimulated for 10 min every day for 7 consecutive days using continuous-wave sonication at a frequency of 1 MHz with spatial and temporal average intensities of 0 (control), 40, 200, 500, or 700 mW cm2. The effects of LIUS on cell proliferation were evaluated by 3H-thymidine incorporation. Proteoglycan synthesis was evaluated by the incorporation of 35S-sulfate and by Safaranin O staining. Collagen synthesis was evaluated by 3H-proline incorporation and immunohistochemistry.
Results: At an intensity of 200 mW cm2, LIUS treatment induced the expression of collagen type II and proteoglycan measured by the incorporation of radioactivity and specific staining of the cartilage explants. However, the expression decreased again at the higher intensities of 500 or 700 mW cm2. Ultrasound had no stimulatory effect on cell proliferation at any intensity.
Conclusion: LIUS has anabolic effects on human cartilage in explant cultures, indicating a potentially important method for the repair of osteoarthritic cartilage.
Objectives – The aim of this study was to compare the effects of antihypertensive agents on cerebral blood flow (CBF) in hypertensive patients with previous ischemic stroke.
Materials and methods – ...In this double‐blind, multi‐center, non‐inferiority trial, 196 patients were randomized to cilnidipine 10–20 mg or losartan 50–100 mg once daily for 4 weeks. Baseline and follow‐up CBF as measured by single photon emission computed tomography were obtained in 167. The primary endpoint was the global CBF change. The secondary endpoints were the CBF change in the hemisphere ipsilateral to the index stroke, non‐impairment of global CBF and blood pressure (BP) reduction.
Results – Global CBF increased significantly in the cilnidipine arm (9.0 ± 29.6%, P = 0.0071) and the losartan arm (11.4 ± 31.4%, P = 0.0012), and these changes were not different between the two groups (P = 0.607). However, the estimated difference in percentage global CBF change between the two groups was −2.43% (97.5% CI, −13.06% to 8.21%), which crossed the predetermined non‐inferiority margin of −8.6%. Ipsilesional hemispheric CBF change, non‐impairment of global CBF and BP reduction were similar in the two groups.
Conclusions – This trial failed to prove the non‐inferiority of cilnidipine to losartan regarding global CBF change. Both the treatments, however, increase the global CBF despite BP lowering.
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