Hypoxia-inducible factor-1α (HIF-1α) is a transcription factor that has a central role in the regulation of tumour metabolism under hypoxic conditions. HIF-1α stimulates glycolytic energy production ...and promotes tumour growth. Sirtuins are NAD(+)-dependent protein deacetylases that regulate cellular metabolism in response to stress; however, their involvement in the hypoxic response remains unclear. In this study, it is shown that SIRT2-mediated deacetylation of HIF-1α regulates its stability in tumour cells. SIRT2 overexpression destabilized HIF-1α under hypoxic conditions, whereas HIF-1α protein levels were high in SIRT2-deficient cells. SIRT2 directly interacted with HIF-1α and deacetylated Lys709 of HIF-1α. Deacetylation of HIF-1α by SIRT2 resulted in increased binding affinity for prolyl hydroxylase 2, a key regulator of HIF-1α stability, and increased HIF-1α hydroxylation and ubiquitination. Moreover, a pharmacological agent that increased the intracellular NAD(+)/NADH ratio led to the degradation of HIF-1α by increasing SIRT2-mediated deacetylation and subsequent hydroxylation. These findings suggest that SIRT2-mediated HIF-1α deacetylation is critical for the destablization of HIF-1α and the hypoxic response of tumour cells.
Summary Objective Cartilage regenerative procedures using the cell-based tissue engineering approach involving mesenchymal stem cells (MSCs) have been receiving increased interest because of their ...potential for altering the progression of osteoarthritis (OA) by repairing cartilage lesions. The aim of this study was to investigate the clinical and magnetic resonance imaging (MRI) outcomes of MSC implantation in OA knees and to determine the association between clinical and MRI outcomes. Design Twenty patients (24 knees) who underwent arthroscopic MSC implantation for cartilage lesions in their OA knees were evaluated at 2 years after surgery. Clinical outcomes were evaluated according to the International Knee Documentation Committee (IKDC) score and the Tegner activity scale, and cartilage repair was assessed according to the MRI Osteoarthritis Knee Score (MOAKS) and Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) score. Results The clinical outcomes significantly improved ( P < 0.001 for both). The cartilage lesion grades (as described in MOAKS grades for size of cartilage-loss area and percentage of full-thickness cartilage loss) at follow-up MRI were significantly better than the preoperative values ( P < 0.001 for both). The clinical outcomes at final follow-up were significantly correlated with the MOAKS and MOCART score at follow-up MRI ( P < 0.05 for all). Conclusions Considering the encouraging clinical and MRI outcomes obtained and the significant correlations noted between the clinical and MRI outcomes, MSC implantation seems to be useful for repairing cartilage lesions in OA knees. However, a larger sample size and long-term studies are needed to confirm our findings.
Objectives
Dietary fiber intake is associated with a lower risk of diabetes, cardiovascular disease, and cancer. However, it is unknown whether dietary fiber has a beneficial effect on preventing the ...development of chronic kidney disease (CKD).
Design, Setting, Participants and Measurements
Using the UK Biobank prospective cohort, 110,412 participants who completed at least one dietary questionnaire and had an estimated glomerular filtration rate ≥60 mL/min/1.73 m
2
, urinary albumin-to-creatinine ratio <30 mg/g, and no history of CKD were included. The primary exposure was total dietary fiber density, calculated by dividing the absolute amount of daily total fiber intake by total energy intake (g/1,000 kcal). We separately examined soluble and insoluble fiber densities as additional predictors. The primary outcome was incident CKD based on diagnosis codes.
Results
A total of 3,507 (3.2%) participants developed incident CKD during a median follow-up of 9.9 years. In a multivariable cause-specific model, the adjusted hazard ratios (aHRs; 95% confidence intervals CIs) for incident CKD were 0.85 (0.77–0.94), 0.78 (0.70–0.86), and 0.76 (0.68–0.86), respectively, for the second, third, and highest quartiles of dietary fiber density (reference: lowest quartile). In a continuous model, the aHR for each +Δ1.0g/1,000 kcal increase in dietary fiber density was 0.97 (95% CI, 0.95–0.99). This pattern of associations was similar for both soluble and insoluble fiber densities and did not differ across subgroups of sex, age, body mass index, hypertension, diabetes, smoking, and inflammation.
Conclusion
Increased fiber intake was associated with a lower risk of CKD in this large well-characterized cohort.
Time-of-flight MR angiography, though widely used after coil embolization, is associated with limitations owing to magnetic susceptibility and radiofrequency shielding following stent-assisted coil ...embolization. We evaluated the pointwise encoding time reduction with radial acquisition (PETRA) sequence in subtraction-based MRA (qMRA) using an ultrashort TE relative to TOF-MRA during the follow-up of stent-assisted coil embolization for anterior circulation aneurysms.
Twenty-five patients (3 men and 22 women; mean age, 59.1 ± 14.0 years) underwent stent-assisted coil embolization for anterior circulation aneurysms and were retrospectively evaluated using TOF-MRA and PETRA qMRA data from the same follow-up session. Two neuroradiologists independently reviewed both MRA findings and subjectively graded flow within the stents (relative to the latest DSA findings) and occlusion status (complete occlusion or neck/aneurysm remnant). Interobserver and intermodality agreement for TOF-MRA and PETRA qMRA were evaluated.
The mean score for flow visualization within the stents was significantly higher in PETRA qMRA than in TOF-MRA (
< .001 for both observers), and good interobserver agreement was reported (κ = 0.63). The aneurysm occlusion status of PETRA qMRA (observer 1, 92.0%; observer 2, 88.0%) was more consistent with DSA than with TOF-MRA (observer 1, 76.0%; observer 2, 80.0%), and there was a better intermodality agreement between DSA and PETRA qMRA than between DSA and TOF-MRA.
These findings indicate that PETRA qMRA is a useful follow-up technique for patients who have undergone stent-assisted coil embolization for anterior circulation aneurysms.
Antibiotic resistance threatens public health worldwide, and inappropriate use of antibiotics is one of the main causes.
To evaluate qualitative use of antibiotics in asymptomatic bacteriuria (ABU) ...and urinary tract infection (UTI).
Cases of positive urine culture (≥105 colony-forning units/mL) performed in inpatient, outpatient and emergency departments in April 2021 were screened in 26 hospitals in the Republic of Korea. The cases were classified as ABU, lower UTI and upper UTI. The appropriateness of antibiotic use was evaluated retrospectively by infectious disease specialists using quality indicators based on clinical guidelines for ABU and UTI.
This study included a total of 2697 patients with ABU or UTI. The appropriateness of antibiotic use was assessed in 1157 patients with ABU, and in 677 and 863 patients with lower and upper UTI, respectively. Among the 1157 patients with ABU, 251 (22%) were prescribed antibiotics without appropriate indications. In 66 patients with ABU in which antibiotics were prescribed with appropriate indications, the duration was adequate in only 23 (34.8%) patients. The appropriateness of empirical and definite antibiotics was noted in 527 (77.8%) and 353 (68.0%) patients with lower UTI, and 745 (86.3%) and 583 (78.2%) patients with upper UTI, respectively. The duration of antibiotics was adequate in 321 (61.8%) patients with lower UTI and 576 (78.7%) patients with upper UTI.
This nationwide qualitative assessment of antibiotic use in ABU and UTI revealed that antibiotics were often prescribed inappropriately, and the duration of antibiotics was unnecessarily prolonged.
A polymerase chain reaction-denaturing gradient gel electrophoresis (PCR-DGGE) technique was used to determine the microfloral composition during the fermentation of kimchi, a traditional Korean ...fermented vegetable food. The kimchi was fermented at 10 °C or 20 °C for 30 or 20 days, respectively. DGGE of the partially amplified 16S rDNA was performed and the most intense bands sequenced. The application of this culture-independent molecular technique determined that the lactic acid bacteria
Weissella confusa, Leuconostoc citreum,
Lactobacillus sakei, and
Lactobacillus curvatus were the main microorganisms responsible for kimchi fermentation.
Objective Fibroepithelial tumours of the breast, which include fibroadenoma (FA) and phyllodes tumour (PT), are benign entities. Although they show different biological behaviours, distinguishing ...between them using imaging features or core needle biopsy (CNB) is challenging. We evaluated sonographic and CNB features, that could be useful for distinguishing between the two. Methods A total of 121 patients with 125 lesions diagnosed as fibroepithelial tumours on ultrasound-guided CNB from March 2017 to April 2020 were studied. Among them, sonographic features of 68 lesions were retrospectively analysed. Clinicopathological results of CNB and surgical excision were reviewed using electronic medical records. Results On ultrasound, tumour size, echogenicity, presence of an internal cleft, vascularity, and elasticity revealed significant differences between FA and PT. Tumour size ≥ 3 cm, presence of an internal cleft, and hard elasticity were common sonographic features in PTs. CNB revealed similar pathological results with surgical excision performed in 61 cases of 68 cases (89%). Conclusion Ultrasonographic features can be useful imaging factors for distinguishing between FA and PT. Ultrasound-guided CNB can replace surgical excision with a high diagnostic accuracy in some cases.
A mobile radon calibration system was developed with a high-sensitivity radon detector, a movable calibration chamber, and a
226
Ra solid source at the Korea Research Institute of Standards and ...Science (KRISS). The high-sensitivity radon detector was based on electrostatic collection mechanism. The volume of the calibration chamber was (1003.8 ± 6.0) L. The mobile radon calibration system was calibrated with
222
Rn CRM from the radon primary system at KRISS. The sensitivities were established to be (231.8 ± 16.1) cpm/(kBq/m
3
) for
218
Po and (254.9 ± 17.8) cpm/(kBq/m
3
) for
214
Po, respectively (
k
= 2).
The cytotoxic effect of the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is limited in some cancer cells, including A549 lung adenocarcinoma cells. However, treatment with TRAIL in ...combination with subtoxic concentrations of sulforaphane (SFN) sensitizes TRAIL-resistant A549 cells to TRAIL-mediated apoptosis. Combined treatment with SFN and TRAIL induced chromatin condensation, DNA fragmentation, annexin V staining and sub-G1 phase DNA content. These indicators of apoptosis correlate with the induction of caspase-3 activity that results in the cleavage of poly(ADP-ribose) polymerase and the release of lactate dehydrogenase. Both the cytotoxic effect and apoptotic characteristics induced by combined treatment were significantly inhibited by z-DEVD-fmk, a caspase-3 inhibitor, demonstrating the important role of caspase-3 in the observed cytotoxic effect. Combined treatment also triggered the activation of p38 MAPK and JNK, and downregulation of ERK and Akt. Inhibitors of ERK (PD98059) or Akt (LY294002), but not p38 MAPK, resulted in significantly decreased cell viability. Although the activation of JNK was increased in response to combined treatment, inhibition of the JNK pathway significantly attenuated cell viability. These results indicate that caspase-3 is a key regulator of apoptosis in response to combined SFN and TRAIL in human lung adenocarcinoma A549 cells through downregulation of ERK and Akt.
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