Resveratrol retards progression of diabetic nephropathy through modulations of oxidative stress, proinflammatory cytokines, and AMP-activated protein kinase

<p>Abstract</p> <p>Background</p> <p>Diabetic nephropathy (DN) has been recognized as the leading cause of end-stage renal disease. Resveratrol (RSV), a polyphenolic compound, has been indicated to possess an insulin-like property in diabetes. In the present study, we aimed to investigate the renoprotective effects of RSV and delineate its underlying mechanism in early-stage DN.</p> <p>Methods</p> <p>The protective effects of RSV on DN were evaluated in streptozotocin (STZ)-induced diabetic rats.</p> <p>Results</p> <p>The plasma glucose, creatinine, and blood urea nitrogen were significantly elevated in STZ-induced diabetic rats. RSV treatment markedly ameliorated hyperglycemia and renal dysfunction in STZ-induced diabetic rats. The diabetes-induced superoxide anion and protein carbonyl levels were also significantly attenuated in RSV-treated diabetic kidney. The AMPK protein phosphorylation and expression levels were remarkably reduced in diabetic renal tissues. In contrast, RSV treatment significantly rescued the AMPK protein expression and phosphorylation compared to non-treated diabetic group. Additionally, hyperglycemia markedly enhanced renal production of proinflammatory cytokine IL-1β. RSV reduced IL-1β but increased TNF-α and IL-6 levels in the diabetic kidneys.</p> <p>Conclusions</p> <p>Our findings suggest that RSV protects against oxidative stress, exhibits concurrent proinflammation and anti-inflammation, and up-regulates AMPK expression and activation, which may contribute to its beneficial effects on the early stage of DN.</p

Spinal Canal Remodeling and Indirect Decompression of Contralateral Foraminal Stenosis After Endoscopic Posterolateral Transforaminal Lumbar Interbody Fusion

Objective There is a lack of literature on indirect decompression in uniportal endoscopic posterolateral transforaminal lumbar interbody fusion (EPTLIF). Our aim is to evaluate the dimensions of the spinal canal and contralateral foramen before and after EPTLIF. Methods This is a retrospective study of patients who underwent EPTLIF in a tertiary spine centre over a 2-year period. The cross-sectional area of the spinal canal and the contralateral foramen at the level of fusion were measured on magnetic resonance imaging scan at 1-day postoperation and at the final follow-up. Patients were grouped according to the decompression performed as per the clinician’s judgement. Results One hundred fifty-two levels of fusion were performed in 120 patients. There was a statistically significant clinical improvement in visual analogue scale and Oswestry Disability Index scores postoperation. The measurements of the spinal canal area were 106.0 mm2, 138.8 mm2, and 195.5 mm2; while contralateral foraminal area were 73.2 mm2, 104.4 mm2, and 120.7 mm2 at preoperation, 1-day postoperation, and at the final follow-up, respectively (p < 0.001). For the subgroup analyses, spinal canal area measurements for the bilateral decompression cohort (n = 35) were 57.0 mm2, 123.9 mm2, and 191.8 mm2; for the ipsilateral decompression cohort (n = 42) were 89.3 mm2, 128.9 mm2, 183.3 mm2; and for the cohort without any decompression and only cage inserted (n = 75) were 138.3 mm2, 151.2 mm2, and 204.1 mm2 (p < 0.001). Contralateral foraminal area measurements were 73.3 mm2, 106.4 mm2 and 120.4 mm2 in the bilateral decompression cohort; 69.5 mm2, 99.0 mm2, 116.9 mm2 in the ipsilateral decompression cohort; and 75.1 mm2, 106.5 mm2, 122.9 mm2 in the cohort without any decompression (p < 0.001). Conclusion Indirect decompression of both the spinal canal and the contralateral foramen can be achieved via EPTLIF. Decompression on an asymptomatic contralateral side is not necessary

A Systematic Study of the Stability, Safety, and Efficacy of the de novo Designed Antimicrobial Peptide PepD2 and Its Modified Derivatives Against Acinetobacter baumannii

Searching for new antimicrobials is a pressing issue to conquer the emergence of multidrug-resistant (MDR) bacteria and fungi. Antimicrobial peptides (AMPs) usually have antimicrobial mechanisms different from those of traditional antibiotics and bring new hope in the discovery of new antimicrobials. In addition to antimicrobial activity, stability and target selectivity are important concerns to decide whether an antimicrobial peptide can be applied in vivo. Here, we used a simple de novo designed peptide, pepD2, which contains only three kinds of amino acid residues (W, K, L), as an example to evaluate how the residues and modifications affect the antimicrobial activity against Acinetobacter baumannii, stability in plasma, and toxicity to human HEK293 cells. We found that pepI2 with a Leu→Ile substitution can decrease the minimum bactericidal concentrations (MBC) against A. baumannii by one half (4 μg/mL). A D-form peptide, pepdD2, in which the D-enantiomers replaced the L-enantiomers of the Lys(K) and Leu(L) residues, extended the peptide half-life in plasma by more than 12-fold. PepD3 is 3-residue shorter than pepD2. Decreasing peptide length did not affect antimicrobial activity but increased the IC50 to HEK293 cells, thus increased the selectivity index (SI) between A. baumannii and HEK293 cells from 4.7 to 8.5. The chain length increase of the N-terminal acyl group and the Lys→Arg substitution greatly enhanced the hemolytic activity, hence those modifications are not good for clinical application. Unlike colistin, the action mechanism of our peptides relies on negatively charged lipids rather than lipopolysaccharides. Therefore, not only gram-negative bacteria but also gram-positive bacteria can be killed by our peptides

Old Technique -New Evidence: Topical agents for musculo-skeletal injuries

The popular use of topical agents for the treatment of musculoskeletal injuries has persisted for centuries but not much scientific evaluations have been done. Since medicinal herbs are particularly popular in Asia, we started a systematic exploration on their choices, and their pharmacological activities; whether transcutaneous transport of bioactive components occur and above all, whether quality clinical evidences could be generated. We found that a search on the vast literature pool would reveal the favourable choices of herbal agents. Biological screening of those selected herbs showed that they probably follow three major common pathways to help with healing after injury, viz, anti-inflammation, pro-angiogenesis and cellular proliferation. Using a simple formula of selected herbs with the ideal bioactivities, evidence based clinical trials could be organized to further prove the efficacy. We have created two such formulae to be put on clinical trial. Our early pilot clinical trials on two minor injuries on the foot and one chronic inflammatory condition have yielded positive data on the value of such topical agents on pain and oedema control, as well as functional maintenance. There was also suggestion of more rapid bone healing. Although limitations exist clear with the small number of study subjects, the positive data and safe application support more studies

Effective Inhibition of Xenografts of Hepatocellular Carcinoma (HepG2) by Rapamycin and Bevacizumab in an Intrahepatic Model

10.1007/s11307-009-0213-4Molecular Imaging and Biology115334-342CPIM

Clinical Efficacy and Post-Treatment Seromarkers Associated with the Risk of Hepatocellular Carcinoma among Chronic Hepatitis C Patients

This follow-up study enrolled chronic hepatitis C patients to evaluate the treatment efficacy and to identify post-treatment seromarkers associated with risk of hepatocellular carcinoma (HCC) among patients with a sustained virological response (SVR) or nonsustained virological response (NSVR). A total of 4639 patients who received pegylated interferon and ribavirin during 2004–2013 were followed until December 2014. HCC was confirmed through health examinations and data linkage with a national database. A total of 233 HCC cases were reported after 26,163 person-years of follow-up, indicating an incidence of 8.9 per 1000 person-years: 6.9 for SVR and 21.6 for NSVR per 1000 person-years. The associated risk of HCC in patients with SVR was 0.37 (0.22–0.63) for those without cirrhosis and 0.54 (0.31–0.92) for those with cirrhosis compared with their respective counterparts with NSVR. Among patients with SVR, advanced age, male gender, cirrhosis, decreased platelet count, and increased aspartate aminotransferase and α-fetoprotein levels were associated with HCC (p < 0.001). The treatment of chronic hepatitis C patients before they developed cirrhosis showed a higher efficacy than did the treatment of those who had already developed cirrhosis. Patients with SVR may still have a risk of HCC and need to be regularly monitored

The Risk of Stroke after Percutaneous Vertebroplasty for Osteoporosis: A Population-Based Cohort Study

PURPOSE: To investigate the incidence and risk of stroke after percutaneous vertebroplasty in patients with osteoporosis. METHODS: A group of 334 patients with osteoporosis, and who underwent percutaneous vertebroplasty during the study period, was compared to 1,655 age-, sex- and propensity score-matched patients who did not undergo vertebroplasty. All demographic covariates and co-morbidities were deliberately matched between the two groups to avoid selection bias. Every subject was followed-up for up to five years for stroke. Adjustments using a Cox regression model and Kaplan-Meier analyses were conducted. RESULTS: A total of 1,989 osteoporotic patients were followed up for 3,760.13 person-years. Overall, the incidence rates of any stroke, hemorrhagic stroke and ischemic stroke were 22.6, 4.2 and 19.6 per 1,000 person-years, respectively. Patients who underwent vertebroplasty were not more likely to have any stroke (crude hazard ratio = 1.13, p = 0.693), hemorrhagic stroke (HR = 2.21, p = 0.170), or ischemic stroke (HR = 0.96, p = 0.90). After adjusting for demographics, co-morbidities and medications, the vertebroplasty group had no significant difference with the comparison group in terms of any, hemorrhagic and ischemic strokes (adjusted HR = 1.22, 3.17, and 0.96, p = 0.518, 0.055, and 0.91, respectively). CONCLUSIONS: Osteoporotic patients who undergo percutaneous vertebroplasty are not at higher risk of any stroke in the next five years after the procedure

Oncologic impact of delay between diagnosis and radical nephroureterectomy

PurposeThis study aimed to evaluate the oncological outcome of delayed surgical wait time from the diagnosis of upper tract urothelial carcinoma (UTUC) to radical nephroureterectomy (RNU).MethodsIn this multicenter retrospective study, medical records were collected between 1988 and 2021 from 18 participating Taiwanese hospitals under the Taiwan UTUC Collaboration Group. Patients were dichotomized into the early (≤90 days) and late (&gt;90 days) surgical wait-time groups. Overall survival, disease-free survival, and bladder recurrence-free survival were calculated using the Kaplan–Meier method and multivariate Cox regression analysis. Multivariate analysis was performed using stepwise linear regression.ResultsOf the 1251 patients, 1181 (94.4%) were classifed into the early surgical wait-time group and 70 (5.6%) into the late surgical wait-time group. The median surgical wait time was 21 days, and the median follow-up was 59.5 months. Our study showed delay-time more than 90 days appeared to be associated with worse overall survival (hazard ratio [HR] 1.974, 95% confidence interval [CI] 1.166−3.343, p = 0.011), and disease-free survival (HR 1.997, 95% CI 1.137−3.507, p = 0.016). This remained as an independent prognostic factor after other confounding factors were adjusted. Age, ECOG performance status, Charlson Comorbidity Index (CCI), surgical margin, tumor location and adjuvant systemic therapy were independent prognostic factors for overall survival. Tumor location and adjuvant systemic therapy were also independent prognostic factors for disease-free survival.ConclusionsFor patients with UTUC undergoing RNU, the surgical wait time should be minimized to less than 90 days. Prolonged delay times may be associated with poor overall and disease-free survival