Oct-4 Expression Maintained Cancer Stem-Like Properties in Lung Cancer-Derived CD133-Positive Cells

CD133 (prominin-1), a 5-transmembrane glycoprotein, has recently been considered to be an important marker that represents the subset population of cancer stem-like cells. Herein we report the isolation of CD133-positive cells (LC-CD133+) and CD133-negative cells (LC-CD133−) from tissue samples of ten patients with non-small cell lung cancer (LC) and five LC cell lines. LC-CD133+ displayed higher Oct-4 expressions with the ability to self-renew and may represent a reservoir with proliferative potential for generating lung cancer cells. Furthermore, LC-CD133+, unlike LC-CD133−, highly co-expressed the multiple drug-resistant marker ABCG2 and showed significant resistance to chemotherapy agents (i.e., cisplatin, etoposide, doxorubicin, and paclitaxel) and radiotherapy. The treatment of Oct-4 siRNA with lentiviral vector can specifically block the capability of LC-CD133+ to form spheres and can further facilitate LC-CD133+ to differentiate into LC-CD133−. In addition, knock-down of Oct-4 expression in LC-CD133+ can significantly inhibit the abilities of tumor invasion and colony formation, and increase apoptotic activities of caspase 3 and poly (ADP-ribose) polymerase (PARP). Finally, in vitro and in vivo studies further confirm that the treatment effect of chemoradiotherapy for LC-CD133+ can be improved by the treatment of Oct-4 siRNA. In conclusion, we demonstrated that Oct-4 expression plays a crucial role in maintaining the self-renewing, cancer stem-like, and chemoradioresistant properties of LC-CD133+. Future research is warranted regarding the up-regulated expression of Oct-4 in LC-CD133+ and malignant lung cancer

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P < 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

NRF2 Deficiency Attenuates Diabetic Kidney Disease in Db/Db Mice via Down-Regulation of Angiotensinogen, SGLT2, CD36, and FABP4 Expression and Lipid Accumulation in Renal Proximal Tubular Cells

The role(s) of nuclear factor erythroid 2-related factor 2 (NRF2) in diabetic kidney disease (DKD) is/are controversial. We hypothesized that Nrf2 deficiency in type 2 diabetes (T2D) db/db mice (db/dbNrf2 knockout (KO)) attenuates DKD progression through the down-regulation of angiotensinogen (AGT), sodium-glucose cotransporter-2 (SGLT2), scavenger receptor CD36, and fatty -acid-binding protein 4 (FABP4), and lipid accumulation in renal proximal tubular cells (RPTCs). Db/dbNrf2 KO mice were studied at 16 weeks of age. Human RPTCs (HK2) with NRF2 KO via CRISPR-Cas9 genome editing and kidneys from patients with or without T2D were examined. Compared with db/db mice, db/dbNrf2 KO mice had lower systolic blood pressure, fasting blood glucose, kidney hypertrophy, glomerular filtration rate, urinary albumin/creatinine ratio, tubular lipid droplet accumulation, and decreased expression of AGT, SGLT2, CD36, and FABP4 in RPTCs. Male and female mice had similar results. NRF2 KO attenuated the stimulatory effect of the Nrf2 activator, oltipraz, on AGT, SGLT2, and CD36 expression and high-glucose/free fatty acid (FFA)-stimulated lipid accumulation in HK2. Kidneys from T2D patients exhibited markedly higher levels of CD36 and FABP4 in RPTCs than kidneys from non-diabetic patients. These data suggest that NRF2 exacerbates DKD through the stimulation of AGT, SGLT2, CD36, and FABP4 expression and lipid accumulation in RPTCs of T2D

Tracing the Accretion Geometry of H1743-322 with Type C Quasiperiodic Oscillations in Multiple Outbursts

We present a systematic analysis of type C quasiperiodic oscillation (QPO) observations of H1743-322 throughout the Rossi X-ray Timing Explorer era. We find that, while different outbursts have significant flux differences, they show consistent positive correlations between the QPO fractional rms amplitude and nonthermal fraction of the emission, which indicate an independence of the intrinsic QPO rms on individual outburst brightnesses in H1743-322. However, the dependence of the QPO rms on frequency is different between the outburst rise and decay phases, where the QPO fractional rms of the decay phase is significantly lower than that of the rise phase at low frequencies. The spectral analysis also reveals different ranges of coronal temperature between the two outburst stages. A semiquantitative analysis shows that the Lense–Thirring precession model could be responsible for the QPO rms differences, requiring a variable coronal geometric shape. However, the variable-Comptonization model could also account for the findings. The fact that the rms differences and the hysteresis traces in the hardness–intensity diagram accompany each other indicates a connection between the two phenomena. By correlating the findings with QPO phase lags and the quasi-simultaneous radio flux previously published, we propose there could be corona-jet transitions in H1743-322 similar to those that have been recently reported in GRS 1915+105

Tracing the Accretion Geometry of H1743-322 with Type C Quasiperiodic Oscillations in Multiple Outbursts

Abstract We present a systematic analysis of type C quasiperiodic oscillation (QPO) observations of H1743-322 throughout the Rossi X-ray Timing Explorer era. We find that, while different outbursts have significant flux differences, they show consistent positive correlations between the QPO fractional rms amplitude and nonthermal fraction of the emission, which indicate an independence of the intrinsic QPO rms on individual outburst brightnesses in H1743-322. However, the dependence of the QPO rms on frequency is different between the outburst rise and decay phases, where the QPO fractional rms of the decay phase is significantly lower than that of the rise phase at low frequencies. The spectral analysis also reveals different ranges of coronal temperature between the two outburst stages. A semiquantitative analysis shows that the Lense–Thirring precession model could be responsible for the QPO rms differences, requiring a variable coronal geometric shape. However, the variable-Comptonization model could also account for the findings. The fact that the rms differences and the hysteresis traces in the hardness–intensity diagram accompany each other indicates a connection between the two phenomena. By correlating the findings with QPO phase lags and the quasi-simultaneous radio flux previously published, we propose there could be corona-jet transitions in H1743-322 similar to those that have been recently reported in GRS 1915+105.</jats:p