The synergistic mechanisms of propofol with cisplatin or doxorubicin in human ovarian cancer cells.

BACKGROUND: Most ovarian cancer cases are diagnosed at an advanced stage, leading to poor outcomes and a relatively low 5-year survival rate. While tumor resection in the early stages can be highly effective, recurrence following primary treatment remains a significant cause of mortality. Propofol is a commonly used intravenous anesthetic agent in cancer resection surgery. Previous research has shown that propofol anesthesia was associated with improved survival in patients undergoing elective surgery for epithelial ovarian cancer. However, the underlying antitumor mechanisms are not yet fully understood. METHODS: This study aimed to uncover the antitumor properties of propofol alone and combined with cisplatin or doxorubicin, in human SKOV3 and OVCAR3 ovarian cancer cells. We applied flowcytometry analysis for mitochondrial membrane potential, apoptosis, and autophagy, colony formation, migration, and western blotting analysis. RESULTS: Given that chemotherapy is a primary clinical approach for managing advanced and recurrent ovarian cancer, it is essential to address the limitations of current chemotherapy, particularly in the use of cisplatin and doxorubicin, which are often constrained by their side effects and the development of resistance. First of all, propofol acted synergistically with cisplatin and doxorubicin in SKOV3 cells. Moreover, our data further showed that propofol suppressed colony formation, disrupted mitochondrial membrane potential, and induced apoptosis and autophagy in SKOV3 and OVCAR3 cells. Finally, the effects of combined propofol with cisplatin or doxorubicin on mitochondrial membrane potential, apoptosis, autophagy, and epithelial-mesenchymal transition were different in SKOV3 and OVCAR3 cells, depending on the p53 status. CONCLUSION: In summary, repurposing propofol could provide novel insights into the existing chemotherapy strategies for ovarian cancer. It holds promise for overcoming resistance to cisplatin or doxorubicin and may potentially reduce the required chemotherapy dosages and associated side effects, thus improving treatment outcomes.

Plasma SCUBE2 as a novel biomarker associates with survival outcomes in patients with sepsis-associated acute kidney injury.

BACKGROUND: The adverse effects of sepsis-associated acute kidney injury (SA-AKI) highlight the need for new biomarkers. Signal Peptide-Complement C1r/C1s, Uegf, Bmp1-Epidermal Growth Factor-like Domain-Containing Protein 2 (SCUBE2), important for angiogenesis and endothelial integrity, has been linked to increased mortality in models of lipopolysaccharide-induced lung injury. This research aimed to assess the utility of plasma SCUBE2 levels as a prognostic indicator for SA-AKI in intensive care unit (ICU) patients. METHODS: Between September 2020 and December 2022, our study enrolled ICU patients diagnosed with stage 3 SA-AKI. We collected demographic information, illness severity indices, and laboratory data, including plasma SCUBE2 and sepsis-triggered cytokine levels. We employed receiver operating characteristic curves and DeLong tests to assess the predictive accuracy for survival, Kaplan-Meier curves to evaluate the relative risk of death, and multivariate logistic regression to identify independent mortality predictors. RESULTS: Among the total of 200 participants, the survivors had significantly higher plasma SCUBE2 levels (115.9 ng/mL) compared to those who died (35.6 ng/mL). SCUBE2 levels showed a positive correlation with the anti-inflammatory cytokine IL-10 and a negative correlation with the APACHE II score, SOFA score, C-reactive protein, and monocyte chemoattractant protein-1. Multivariate analysis revealed that elevated SCUBE2 and IL-10 levels were independently protective against mortality, and associated with the most favorable 30-day survival outcomes. CONCLUSIONS: In ICU patients with stage 3 SA-AKI, lower plasma levels of SCUBE2 were correlated with elevated pro-inflammatory factors, which impacted survival outcomes. This suggests that SCUBE2 could be a potential biomarker for predicting prognosis in patients with SA-AKI.

Associations of urinary fetuin-A with histopathology and kidney events in biopsy-proven kidney disease.

Background: Fetuin-A is implicated in the pathogenesis of vascular calcification in chronic kidney disease (CKD); however, the relationship between fetuin-A, histopathologic lesions and long-term kidney outcomes in patients with various types of kidney disease remains unclear. Methods: We measured urinary fetuin-A levels in 335 individuals undergoing clinically indicated native kidney biopsy. The expressions of fetuin-A mRNA and protein in the kidney were assessed using RNA sequencing and immunohistochemistry. The association of urinary fetuin-A with histopathologic lesions and major adverse kidney events (MAKE), defined as a decline in estimated glomerular filtration rate (eGFR) of at least 40%, kidney failure or death, was analyzed. Results: Urinary fetuin-A levels showed a positive correlation with albuminuria (rs = 0.67, P < .001) and a negative correlation with eGFR (rs = -0.46, P < .001). After multivariate adjustment, higher urinary fetuin-A levels were associated with glomerular inflammation, mesangial expansion, interstitial fibrosis and tubular atrophy, and arteriolar sclerosis. Using a 1 transcript per million gene expression cutoff, we found kidney fetuin-A mRNA levels below the threshold in both individuals with normal kidney function and those with CKD. Additionally, immunohistochemistry revealed reduced fetuin-A staining in tubular cells of CKD patients compared with normal controls. During a median 21-month follow-up, 115 patients experienced MAKE, and Cox regression analysis confirmed a significant association between elevated urinary fetuin-A and MAKE. This association remained significant after adjusting for potential confounding factors. Conclusion: Urinary fetuin-A is associated with chronic histological damage and adverse clinical outcomes across a spectrum of biopsy-proven kidney diseases.

Propofol-based total intravenous anesthesia is associated with less postoperative recurrence than desflurane anesthesia in thyroid cancer surgery.

BACKGROUND: The effects of anesthesia in patients undergoing thyroid cancer surgery are still not known. We investigated the relationship between the type of anesthesia and patient outcomes following elective thyroid cancer surgery. METHODS: This was a retrospective cohort study of patients who underwent elective surgical resection for papillary thyroid carcinoma between January 2009 and December 2019. Patients were grouped according to the type of anesthesia they received, desflurane or propofol. A Kaplan-Meier analysis was conducted, and survival/recurrence curves were presented from the date of surgery to death/recurrence. Univariable and multivariable Cox regression models were used to compare hazard ratios for recurrence after propensity matching. RESULTS: A total of 621 patients (22 deaths, 3.5%) under desflurane anesthesia and 588 patients (32 deaths, 5.4%) under propofol anesthesia were included. Five hundred and eighty-eight patients remained in each group after propensity matching. Propofol anesthesia was not associated with better survival compared to desflurane anesthesia in the matched analysis (P = 0.086). However, propofol anesthesia was associated with less recurrence (hazard ratio, 0.38; 95% confidence interval, 0.25-0.56; P < 0.001) in the matched analysis. CONCLUSIONS: Propofol anesthesia was associated with less recurrence, but not mortality, following surgery for papillary thyroid carcinoma than desflurane anesthesia. Further prospective investigation is needed to examine the influence of propofol anesthesia on patient outcomes following thyroid cancer surgery.

Comparison of radiographic and clinical outcomes between ALIF, OLIF, and TLIF over 2-year follow-up: a comparative study.

BACKGROUND: Regarding the increasing adoption of oblique lateral interbody fusion (OLIF) for treating degenerative lumbar disorders, we aimed to evaluate whether OLIF, one of the options for anterolateral approach lumbar interbody fusion, demonstrate clinical superiority over anterior lumbar interbody fusion (ALIF) or posterior approach, represented by transforaminal lumbar interbody fusion (TLIF). METHODS: Patients who received ALIF, OLIF, and TLIF for symptomatic degenerative lumbar disorders during the period 2017-2019 were identified. Radiographic, perioperative, and clinical outcomes were recorded and compared during 2-year follow-up. RESULTS: A total of 348 patients with 501 correction levels were enrolled in the study. Fundamental sagittal alignment profiles were substantially improved at 2-year follow-up, particularly in the anterolateral approach (A/OLIF) group. The Oswestry disability index (ODI) and EuroQol-5 dimension (EQ-5D) in the ALIF group were superior when compared to the OLIF and TLIF group 2-year following surgery. However, comparisons of VAS-Total, VAS-Back, and VAS-Leg revealed no statistically significance across all approaches. TLIF demonstrated highest subsidence rate of 16%, while OLIF had least blood loss and was suitable for high body mass index patients. CONCLUSIONS: Regarding treatment for degenerative lumbar disorders, ALIF of anterolateral approach demonstrated superb alignment correction and clinical outcome. Comparing to TLIF, OLIF possessed advantage in reducing blood loss, restoring sagittal profiles and the accessibility at all lumbar level while simultaneously achieving comparable clinical improvement. Patient selection in accordance with baseline conditions, and surgeon preference both remain crucial issues circumventing surgical approach strategy.

Tumor Necrosis Factor Alpha: Implications of Anesthesia on Cancers.

Cancer remains a major public health issue and a leading cause of death worldwide. Despite advancements in chemotherapy, radiation therapy, and immunotherapy, surgery is the mainstay of cancer treatment for solid tumors. However, tumor cells are known to disseminate into the vascular and lymphatic systems during surgical manipulation. Additionally, surgery-induced stress responses can produce an immunosuppressive environment that is favorable for cancer relapse. Up to 90% of cancer-related deaths are the result of metastatic disease after surgical resection. Emerging evidence shows that the interactions between tumor cells and the tumor microenvironment (TME) not only play decisive roles in tumor initiation, progression, and metastasis but also have profound effects on therapeutic efficacy. Tumor necrosis factor alpha (TNF-α), a pleiotropic cytokine contributing to both physiological and pathological processes, is one of the main mediators of inflammation-associated carcinogenesis in the TME. Because TNF-α signaling may modulate the course of cancer, it can be therapeutically targeted to ameliorate clinical outcomes. As the incidence of cancer continues to grow, approximately 80% of cancer patients require anesthesia during cancer care for diagnostic, therapeutic, or palliative procedures, and over 60% of cancer patients receive anesthesia for primary surgical resection. Numerous studies have demonstrated that perioperative management, including surgical manipulation, anesthetics/analgesics, and other supportive care, may alter the TME and cancer progression by affecting inflammatory or immune responses during cancer surgery, but the literature about the impact of anesthesia on the TNF-α production and cancer progression is limited. Therefore, this review summarizes the current knowledge of the implications of anesthesia on cancers from the insights of TNF-α release and provides future anesthetic strategies for improving oncological survival.

Comparison of Single Target-Controlled Infusion Pump-Delivered Mixed Propofol and Remifentanil with Two Target-Controlled Infusion Pumps-Delivered Propofol and Remifentanil in Patients Undergoing Breast Cancer Surgery-A Prospective Study.

Total intravenous anesthesia (TIVA) with remifentanil and propofol (RP) is considered to be an ideal type of general anesthesia (GA) for pediatric and adult patients undergoing medical procedures. However, delivery of an RP mixture by target-controlled infusion (TCI) for GA in surgical procedures has not been described. We investigated the merit of this approach for breast cancer surgery. Eighty-four patients (n = 42 per group) were randomly allocated to propofol and remifentanil either delivered by separate TCI pumps (S group) or in an RP mixture by a single TCI pump (M group). Dosages were adjusted based on the bispectral index (BIS) and the analgesia nociception index (ANI). The primary outcomes were adequate anesthesia (BIS 40-60 and ANI 50-70, respectively), acceptable hemodynamic fluctuations (<30% of baseline) with less frequent TCI pump adjustments, bolus injections of anesthetics, and total consumption of anesthetics during the procedure. The secondary endpoints included time of emergence from anesthesia, patient satisfaction, postoperative pain, rescue with opioids, and adverse events. The characteristics of patients, hemodynamic parameters, BIS and ANI scores, duration of surgery, anesthesia, and emergence were not significantly different between groups. The adjustment frequency of TCI was significantly higher in the S group (3 (range 0-6) vs. 2 (0-6) times; p = 0.005). The total dosage of anesthetics, pain rating, patient satisfaction, need for opioids postoperatively, and incidence of adverse events were not significantly different. We have demonstrated that this RP mixture provided adequate hypnotic and analgesic effects under BIS and ANI monitoring in patients undergoing breast cancer surgery within 1 h.

Plasma Galectin-9 Is a Useful Biomarker for Predicting Renal Function in Patients Undergoing Native Kidney Biopsy.

CONTEXT.­: Galectin-9 reduces tissue damage in certain immune-mediated glomerular diseases. However, its role in structural and functional renal changes in patients with varying types of chronic kidney disease (CKD) is less clear. OBJECTIVE.­: To investigate the association between plasma galectin-9 levels, proteinuria, tubulointerstitial lesions, and renal function in different CKD stages. DESIGN.­: We measured plasma galectin-9 levels in 243 patients undergoing renal biopsy for determining the CKD etiology. mRNA and protein expression levels of intrarenal galectin-9 were assessed by quantitative real-time polymerase chain reaction and immunostaining. Relationships between plasma galectin-9, clinical characteristics, and tubulointerstitial damage were analyzed with logistic regression. We investigated galectin-9 expression patterns in vitro in murine J774 macrophages treated with differing stimuli. RESULTS.­: To analyze the relationship between galectin-9 and clinical features, we divided the patients into 2 groups according to median plasma galectin-9 levels. The high galectin-9 group tended to be older and to have decreased renal function, higher proteinuria, and greater interstitial fibrosis. After multivariable adjustment, elevated plasma galectin-9 levels were independently associated with stage 3b or higher CKD. An analysis of gene expression in the tubulointerstitial compartment in the biopsy samples showed a significant positive correlation between intrarenal galectin-9 mRNA expression and plasma galectin-9 levels. Immunohistochemistry confirmed increased galectin-9 expression in the renal interstitium of patients with advanced CKD, and most galectin-9-positive cells were macrophages, as determined by double-immunofluorescence staining. In vitro experiments showed that galectin-9 expression in macrophages was significantly increased after interferon-γ stimulation. CONCLUSIONS.­: Our findings suggest that plasma galectin-9 is a good biomarker for diagnosing advanced CKD.

Propofol-based total intravenous anesthesia is associated with better survival than desflurane anesthesia in limb-salvage surgery for osteosarcoma: A retrospective analysis.

Previous studies have demonstrated that anesthetic techniques can affect the outcomes of cancer surgery. We investigated the association between anesthetic techniques and patient outcomes after elective limb-salvage surgery for osteosarcoma (OS). This was a retrospective cohort study of patients who underwent elective limb-salvage surgery for OS between January 2007 and December 2018. Patients were grouped according to the administration of propofol-based total intravenous anesthesia (TIVA) or desflurane (DES) anesthesia. Kaplan-Meier analysis was performed, and survival curves were constructed from the date of surgery to death. Univariate and multivariate Cox regression models were applied to compare the hazard ratios (HRs) for death after propensity matching. Subgroup analyses were done for postoperative recurrence, metastasis, and tumor-node-metastasis (TNM) staging. A total of 30 patients (17 deaths, 56.7%) who received DES anesthesia and 26 (4 deaths, 15.4%) who received TIVA were eligible for analysis. After propensity matching, 22 patients were included in each group. In the matched analysis, patients who received TIVA had better survival with a HR of 0.30 (95% confidence interval [CI], 0.11-0.81; P = .018). Subgroup analyses also showed significantly better survival in the presence of postoperative metastasis (HR, 0.24; 95% CI, 0.06-0.87; P = .030) and with TNM stage II to III (HR, 0.26; 95% CI, 0.09-0.73; P = .011) in the matched TIVA group. In addition, patients administered with TIVA had lower risks of postoperative recurrence and metastasis than those administered with DES anesthesia in the matched analyses. Propofol-based TIVA was associated with better survival in patients who underwent elective limb-salvage surgery for OS than DES anesthesia. Prospective studies are needed to assess the effects of TIVA on oncological outcomes in patients with OS.

Urinary Galectin-3 as a Novel Biomarker for the Prediction of Renal Fibrosis and Kidney Disease Progression.

Plasma galectin-3 (Gal-3) is associated with organ fibrosis, but whether urinary Gal-3 is a potential biomarker of kidney disease progression has never been explored. Between 2018 and 2021, we prospectively enrolled 280 patients who underwent renal biopsy and were divided into three groups based on their urinary Gal-3 levels (<354.6, 354.6−510.7, and ≥510.8 pg/mL) to assess kidney disease progression (defined as ≥40% decline in the estimated glomerular filtration rate or end-stage renal disease) and renal histology findings. Patients in the highest urinary Gal-3 tertile had the lowest eGFRs and highest proteinuria levels. In multivariate Cox regression models, patients in the highest tertile had the highest risk of kidney disease progression (adjusted hazard ratio, 4.60; 95% confidence interval, 2.85−7.71) compared to those in the lowest tertile. Higher urinary Gal-3 levels were associated with more severe renal fibrosis. Intrarenal mRNA expression of LGALS3 (Gal-3-encoded gene) was most correlated with the renal stress biomarkers (IGFBP7 and TIMB2), renal function biomarkers (PTGDS) and fibrosis-associated genes (TGFB1). The urinary Gal-3 level may be useful for the identification of patients at high risk of kidney disease progression and renal fibrosis, and for the early initiation of treatments for these patients.

Dose-response effects of physical activity on all-cause mortality and major cardiorenal outcomes in chronic kidney disease.

AIMS: Physical activity has a protective effect against mortality and cardiovascular events in chronic kidney disease (CKD) patients. Nonetheless, how different levels of physical activity affect the health benefits in CKD remains unclear. This study aimed to investigate the dose-response effects of physical activity on mortality and major cardiorenal events in CKD. METHODS AND RESULTS: We evaluated a longitudinal cohort of 4508 Taiwanese CKD patients between 2004 and 2017. Physical activity was assessed by the NHANES questionnaire and quantified in metabolic equivalent-hours per week (MET-hour/week). Patients were categorized into highly active (≥7.5 MET-h/week), low-active (0.1 to <7.5 MET-h/week), or inactive (0 MET-h/week) groups. Cox regression and restricted cubic spline models were utilized to explore the association between physical activity and the risks of study outcomes, including all-cause mortality, end-stage renal disease (ESRD), and major adverse cardiovascular events (MACE, a composite of cardiovascular death, myocardial infarction, ischaemic stroke, and hospitalized heart failure). During a median follow-up of 686 days, 739 death, 1059 ESRD, and 521 MACE events occurred. Highly active group had the lowest chance of all study outcomes, followed by low-active and inactive groups (P < 0.001). Multivariable Cox regression showed that only highly active group was independently associated with lower risks for all-cause mortality [hazard ratio (HR) 0.62; 95% confidence interval (CI) 0.53-0.74], ESRD (HR 0.83, 95% CI 0.72-0.96), and MACE (HR 0.63, 95% CI 0.51-0.76) compared to the inactive group. The risks of MACE did not further decrease once physical activity surpassed 15 MET-h/week, indicating a U-shaped association. The results were consistent in the subgroup and sensitivity analyses. CONCLUSION: Physical activity of 7.5 to <15 MET-h/week is associated with lower risks of adverse cardiorenal outcomes and should be integrated into the care of CKD.

Identification of Galectin-3 as Potential Biomarkers for Renal Fibrosis by RNA-Sequencing and Clinicopathologic Findings of Kidney Biopsy.

Background: Galectin-3 (Gal-3) is a multifunctional glycan-binding protein shown to be linked to chronic inflammation and fibrogenesis. Plasma Gal-3 is associated with proteinuria and renal dysfunction, but its role has never been confirmed with kidney biopsy results. In our study, we aimed to explore the expression of Gal-3 in biopsy-proven patients, and we tested the hypothesis that chronic kidney disease (CKD) leads to upregulation of plasma Gal-3 expression in corresponding biopsy findings and RNA sequencing analysis. Method: In 249 patients (male/female: 155/94, age: 57.2 ± 16.3 years) who underwent kidney biopsy, plasma levels of Gal-3 were measured to estimate the association of renal fibrosis. Relationships between plasma Gal-3 levels, estimated glomerular filtration rate (eGFR) and renal histology findings were also assessed. We further examined the gene expression of Gal-3 in RNA-sequencing analysis in biopsy-proven patients. Results: Compared to patients without CKD, CKD patients had higher levels of plasma Gal-3 (1,016.3 ± 628.1 pg/mL vs. 811.6 ± 369.6 pg/ml; P = 0.010). Plasma Gal-3 was inversely correlated with eGFR (P = 0.005) but not with proteinuria. Higher Gal-3 levels were associated with interstitial fibrosis, tubular atrophy and vascular intimal fibrosis. RNA-sequencing analysis showed the upregulation of Gal-3 in fibrotic kidney biopsy samples, and the differentially expressed genes were mainly enhanced in immune cell activation and the regulation of cell-cell adhesion. Conclusions: Plasma Gal-3 levels are inverse correlated with eGFR but positively correlated with renal fibrosis, which may be involved in the immune response and associated pathways. These findings support the role of Gal-3 as a predictive marker of renal fibrosis.

Propofol-Based Total Intravenous Anesthesia is Associated with Better Survival than Desflurane Anesthesia in Epithelial Ovarian Cancer Surgery: A Retrospective Cohort Study.

Background: Previous studies have shown that anesthetic techniques can affect outcomes of cancer surgery. We investigated the association between anesthetic techniques and patient outcomes after elective epithelial ovarian cancer surgery. Methods: This was a retrospective cohort study of patients who received elective open surgery for epithelial ovarian cancer between January 2009 and December 2014. Patients were grouped according to the administration of propofol or desflurane anesthesia. Kaplan-Meier analysis was performed, and survival curves were constructed from the date of surgery to death. Univariate and multivariate Cox regression models were used to compare hazard ratios for death after propensity matching. Subgroup analyses were performed for age, body mass index, preoperative carbohydrate antigen-125 level, International Federation of Gynecology and Obstetrics staging, and operation and anesthesia time. Results: In total, 165 patients (76 deaths, 46.1%) who received desflurane anesthesia and 119 (30 deaths, 25.2%) who received propofol anesthesia were eligible for analysis. After propensity matching, 104 patients were included in each group. In the matched analysis, patients who received propofol anesthesia had better survival with a hazard ratio of 0.52 (95% confidence interval, 0.33-0.81; p = 0.005). Subgroup analyses also showed significantly better survival with old age, high body mass index, elevated carbohydrate antigen-125 level, advanced International Federation of Gynecology and Obstetrics stage, and prolonged operation and anesthesia time in the matched propofol group. In addition, patients administered with propofol anesthesia had less postoperative recurrence and metastasis than those administered with desflurane anesthesia in the matched analysis. Conclusion: Propofol anesthesia was associated with better survival in patients who underwent elective epithelial ovarian cancer open surgery. Prospective studies are warranted to evaluate the effects of propofol anesthesia on oncological outcomes in patients with epithelial ovarian cancer.

Hypoxic mesenchymal stem cells ameliorate acute kidney ischemia-reperfusion injury via enhancing renal tubular autophagy.

BACKGROUND: Acute kidney injury (AKI) is an emerging global healthcare issue without effective therapy yet. Autophagy recycles damaged organelles and helps maintain tissue homeostasis in acute renal ischemia-reperfusion (I/R) injury. Hypoxic mesenchymal stem cells (HMSCs) represent an innovative cell-based therapy in AKI. Moreover, the conditioned medium of HMSCs (HMSC-CM) rich in beneficial trophic factors may serve as a cell-free alternative therapy. Nonetheless, whether HMSCs or HMSC-CM mitigate renal I/R injury via modulating tubular autophagy remains unclear. METHODS: Renal I/R injury was induced by clamping of the left renal artery with right nephrectomy in male Sprague-Dawley rats. The rats were injected with either PBS, HMSCs, or HMSC-CM immediately after the surgery and sacrificed 48 h later. Renal tubular NRK-52E cells subjected to hypoxia-reoxygenation (H/R) injury were co-cultured with HMSCs or treated with HMSC-CM to assess the regulatory effects of HSMCs on tubular autophagy and apoptosis. The association of tubular autophagy gene expression and renal recovery was also investigated in patients with ischemic AKI. RESULT: HMSCs had a superior anti-oxidative effect in I/R-injured rat kidneys as compared to normoxia-cultured mesenchymal stem cells. HMSCs further attenuated renal macrophage infiltration and inflammation, reduced tubular apoptosis, enhanced tubular proliferation, and improved kidney function decline in rats with renal I/R injury. Moreover, HMSCs suppressed superoxide formation, reduced DNA damage and lipid peroxidation, and increased anti-oxidants expression in renal tubular epithelial cells during I/R injury. Co-culture of HMSCs with H/R-injured NRK-52E cells also lessened tubular cell death. Mechanistically, HMSCs downregulated the expression of pro-inflammatory interleukin-1ß, proapoptotic Bax, and caspase 3. Notably, HMSCs also upregulated the expression of autophagy-related LC3B, Atg5 and Beclin 1 in renal tubular cells both in vivo and in vitro. Addition of 3-methyladenine suppressed the activity of autophagy and abrogated the renoprotective effects of HMSCs. The renoprotective effect of tubular autophagy was further validated in patients with ischemic AKI. AKI patients with higher renal LC3B expression were associated with better renal recovery. CONCLUSION: The present study describes that the enhancing effect of MSCs, and especially of HMCSs, on tissue autophagy can be applied to suppress renal tubular apoptosis and attenuate renal impairment during renal I/R injury in the rat. Our findings provide further mechanistic support to HMSCs therapy and its investigation in clinical trials of ischemic AKI.

Comparison of Simplified Creatinine Index and Systemic Inflammatory Markers for Nutritional Evaluation of Hemodialysis Patients.

Protein-energy wasting (PEW) is associated with adverse outcomes in hemodialysis patients. This study compares the simplified creatinine index (SCI) and circulating inflammatory markers as nutritional screening tools for hemodialysis patients. Maintenance hemodialysis patients (230 total patients, 34.8% women, 64.0 ± 14.3 years old) from a tertiary medical center were assessed for demographic data, body composition analysis, biochemistry tests, and circulating inflammatory biomarkers. The SCI was calculated using Canaud's formula. Reduced fat-free mass index (FFMI), a surrogate of lean body mass, was identified according to the European Society for Clinical Nutrition and Metabolism guidelines. Nutritional status was assessed by the geriatric nutritional risk index (GNRI) and International Society of Renal Nutrition and Metabolism (ISRNM) criteria. Multivariate logistic regression revealed independent risk factors for low FFMI and malnutrition. Of the patients, 47.4% had low FFMI. Patients with a reduction in FFMI tended to be older females with lower body mass index, SCI, and GNRI scores but significantly higher levels of interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), and IL-8. SCI was found to be an independent predictor for reduced FFMI (OR 0.57, 95% CI 0.40-0.81) and presence of PEW according to ISRNM criteria (OR 0.38, 95% CI 0.21-0.68). Although a positive association between systemic inflammatory markers and low FFMI was observed, this association disappeared in multivariate analysis. Moreover, the inflammatory markers examined in this study were not associated with malnutrition after adjusting for potential confounders. Compared with markers of systemic inflammation, SCI achieved better performance in assessing the nutritional status of hemodialysis patients.

Utilization of Nanoporous Nickel Oxide as the Hole Injection Layer for Quantum Dot Light-Emitting Diodes.

Nickel oxide (NiOx) has been extensively investigated as the hole injection layer (HIL) for many optoelectronic devices because of its excellent hole mobility, high environmental stability, and low-cost fabrication. In this research, a NiOx thin film and nanoporous layers (NPLs) have been utilized as the HIL for the fabrication of quantum dot light-emitting diodes (QLEDs). The obtained NiOx NPLs have spongelike nanostructures that possess a larger surface area to enhance carrier injection and to lower the turn-on voltage as compared with the NiOx thin film. The energy levels of NiOx were slightly downshifted by incorporating the nanoporous structure. The amount of Ni2O3 species is higher than that of NiO in the NiOx NPL, confirming its good hole transport ability. The best QLED was achieved with a 30 nm thick NiOx NPL, exhibiting a maximum brightness of 68 646 cd m-2, a current efficiency of 7.60 cd A-1, and a low turn-on voltage of 3.4 V. More balanced carrier transport from the NiOx NPL and ZnO NPs/polyethylenimine ethoxylated (PEIE) is responsible for the improved device performance.

Adjunctive dexmedetomidine infusion in open living donor hepatectomy: A way to enhance postoperative analgesia and recovery.

BACKGROUND: Open living donor hepatectomy (OLDH) is a highly painful procedure. Advanced strategies for enhancing perioperative analgesia and accelerating recovery are needed for patients undergoing OLDH. This study evaluated the effects of intravenous infusion of dexmedetomidine (DEX) during OLDH on postoperative analgesia and recovery. METHODS: This prospective, randomised, double-blinded, and placebo-controlled study included 34 patients randomised to a control group (group C) and a DEX group (group D). Utilisation of intravenous patient-controlled analgesia (IV-PCA) pump, pain intensity, and postoperative recovery variables were recorded. Moreover, intraoperative anaesthetic consumption, hemodynamic parameters, and fluid status were also recorded. RESULTS: During the first 24 hours after surgery, patients in group D had a lower pain intensity. The cumulative numbers of IV-PCA pump presses and fentanyl consumption within 24 and 48 hours postoperatively in group C were significantly higher than in group D. The time to first IV-PCA attempt was prolonged in group D. In addition, faster flatus passage was observed in group D. Intraoperatively, fewer anaesthetic agents were required in group D. Less fluctuation in hemodynamics and reduced bleeding were also found in group D. CONCLUSIONS: The present study revealed that the addition of intravenous infusion of DEX during OLDH provided several benefits in relieving postoperative pain and promoting recovery. Therefore, we concluded that intraoperative DEX infusion may play an important role in enhancing the recovery of patients undergoing OLDH.

Trichostatin A Alleviates Renal Interstitial Fibrosis Through Modulation of the M2 Macrophage Subpopulation.

Mounting evidence indicates that an increase in histone deacetylation contributes to renal fibrosis. Although inhibition of histone deacetylase (HDAC) can reduce the extent of fibrosis, whether HDAC inhibitors exert the antifibrotic effect through modulating the phenotypes of macrophages, the key regulator of renal fibrosis, remains unknown. Moreover, the functional roles of the M2 macrophage subpopulation in fibrotic kidney diseases remain incompletely understood. Herein, we investigated the role of HDAC inhibitors on renal fibrogenesis and macrophage plasticity. We found that HDAC inhibition by trichostatin A (TSA) reduced the accumulation of interstitial macrophages, suppressed the activation of myofibroblasts and attenuated the extent of fibrosis in obstructive nephropathy. Moreover, TSA inhibited M1 macrophages and augmented M2 macrophage infiltration in fibrotic kidney tissue. Interestingly, TSA preferentially upregulated M2c macrophages and suppressed M2a macrophages in the obstructed kidneys, which was correlated with a reduction of interstitial fibrosis. TSA also repressed the expression of proinflammatory and profibrotic molecules in cultured M2a macrophages and inhibited the activation of renal myofibroblasts. In conclusion, our study was the first to show that HDAC inhibition by TSA alleviates renal fibrosis in obstructed kidneys through facilitating an M1 to M2c macrophage transition.