Correction: Huang et al. Systemic Anticoagulation and Inpatient Outcomes of Pancreatic Cancer: Real-World Evidence from U.S. Nationwide Inpatient Sample. Cancers 2023, 15, 1985.

In the original publication [...].

The effects of incretin-based therapies on weight reduction and metabolic parameters in children with obesity: A systematic review and meta-analysis.

BACKGROUND: Growing evidence indicates that incretin-based therapies (IBTs), glucagon-like peptide-1 receptor agonists (GLP-1 RAs), and dipeptidyl peptidase-4 inhibitors (DPP4is) are effective and safe for treating pediatric obesity patients with or without type 2 diabetes. Therefore, we aimed to perform a systematic review and meta-analysis for updating current evidence. METHODS: We searched the PubMed, the Cochrane Library, and the EMBASE database for articles published until September 15, 2023, and limited to randomized control trials. The primary outcomes were changed from baseline in weight metrics and the cardiometabolic profile. A random effects model will be used, as high heterogeneity is expected. All analyses were performed using STATA 17.0. RESULTS: Fifteen trials with a total number of 1286 participants were included in our meta-analysis. Overall, the mean difference in weight change between the IBTs group and the control group was -2.89 kg (95% confidence interval, -5.12 to -0.65, p = 0.011). Additionally, IBTs significantly reduced the HbA1c level and fasting plasma glucose by 0.37% and 6.99 mg/dl, compared with control groups. IBTs showed a little increased risk of GI side effects and hypoglycemia events, but none of the severe hypoglycemia events were occurred in IBTs group. CONCLUSIONS: Our study results have proved that GLP-1 RAs are safe, acceptable, and effective in weight reduction and sugar control for children with obesity. In addition, DPP-4is seems to have no effect on glycemic control and weight loss in childhood obesity. Further research is needed to confirm these findings, especially in younger children.

Systemic Anticoagulation and Inpatient Outcomes of Pancreatic Cancer: Real-World Evidence from U.S. Nationwide Inpatient Sample.

Background: Pancreatic cancer can induce a hypercoagulable state which may lead to clinically apparent thrombosis. However, the effect of anticoagulants remains ambiguous. This study aimed to investigate the potential effect of long-term systemic anticoagulant usage on hospitalization outcomes of patients with pancreatic cancer. Methods: This retrospective study extracted all data from the U.S. Nationwide Inpatient Sample (NIS) database from 2005 to 2018. We included hospitalized adults ≥18 years old with a pancreatic cancer diagnosis identified by International Classification of Diseases ninth revision (ICD-9) and tenth revision (ICD-10) codes. We utilized diagnostic codes ICD9 V58.61 and ICD10 Z79.01, i.e., 'long-term use of anticoagulant', to identify individuals who were on a long-term systemic anticoagulant. The study cohort were then further grouped as being with or without long-term systemic use of an anticoagulant. Propensity score matching was performed to balance the characteristics of the two groups. The risks of life-threatening events, e.g., acute myocardial infarction (AMI), acute heart failure (AHF), sepsis, shock, and acute kidney injury (AKI), in-hospital death, and prolonged length of stay (LOS) in the hospital were compared between the groups by univariable and multivariable logistic regression analyses. Results: The study population consisted of 242,903 hospitalized patients with pancreas cancer, 6.5% (n = 15,719) of whom were on long-term systemic anticoagulants. A multivariable regression analysis showed that long-term systemic anticoagulant use was independently associated with lower odds of sepsis (aOR: 0.81, 95% CI: 0.76-0.85), shock (aOR: 0.59, 95% CI: 0.51-0.68), AKI (aOR: 0.86, 95% CI: 0.81-0.91), in-hospital mortality (aOR: 0.65, 95% CI: 0.60-0.70), and prolonged LOS (aOR: 0.84, 95% CI: 0.80-0.89). Conclusions: Long-term systemic anticoagulant use is associated with better clinical outcomes in terms of decreased risks of some life-threatening events, in-hospital death, and prolonged LOS among hospitalized patients with pancreatic cancer in the U.S.

Noise-induced hearing loss profile among Taiwan Airforce on duty pilots.

PURPOSE: Noise-induced hearing loss (NIHL) often results in impaired functional hearing and accidental injuries; thus, reducing military performance and endangering flight safety. While a few studies addressing laterality (left-right ear differences) and NIHL incidence between fixed-winged (jet-fighter) and rotary-wing (helicopter) aircrafts yielded inconsistent results, little is known about the NIHL profile among different types of jet-fighter pilots. This study aims to conduct a fine-grained examination of NIHL among Airforce jet pilots, with planned comparisons of laterality and aircraft type, along with the goal to compare the sensitivity of different hearing indices in predicting military pilot NIHL. MATERIALS AND METHODS: This cross-sectional study utilizes the health and hearing data of 1025 Taiwanese Air Force Military pilots from the 2019 Taiwanese physical examination database to assess the changes in their hearing thresholds, and evaluate their risk for NIHL. RESULTS: Our results showed that, among available military aircraft types, the trainer aircraft and M2000-5 jet-fighter had the highest risk of NIHL, in addition to a left ear inferiority found in the overall population of military pilots. Among the three hearing indices used in this study -the International Organization for Standardization (ISO) three-point hearing index, the Occupational Safety and Health Administration (OSHA) three-point hearing index, and the American Academy of Otolaryngology-Head and Neck Surgery's (AAO-HNS) high-frequency three-point hearing index-, the OSHA the AAO-HNS were the most sensitive. CONCLUSION: Our results suggest a better noise protection for trainer and M2000-5 pilots, especially for the left ear, is warranted.

Disulfiram/Copper Suppresses Cancer Stem Cell Activity in Differentiated Thyroid Cancer Cells by Inhibiting BMI1 Expression.

Differentiated thyroid carcinomas (DTCs), which have papillary and follicular types, are common endocrine malignancies worldwide. Cancer stem cells (CSCs) are a particular type of cancer cells within bulk tumors involved in cancer initiation, drug resistance, and metastasis. Cells with high intracellular aldehyde hydrogenase (ALDH) activity are a population of CSCs in DTCs. Disulfiram (DSF), an ALDH inhibitor used for the treatment of alcoholism, reportedly targets CSCs in various cancers when combined with copper. This study reported for the first time that DSF/copper can inhibit the proliferation of papillary and follicular DTC lines. DSF/copper suppressed thyrosphere formation, indicating the inhibition of CSC activity. Molecular mechanisms of DSF/copper involved downregulating the expression of B lymphoma Mo-MLV insertion region 1 homolog (BMI1) and cell cycle-related proteins, including cyclin B2, cyclin-dependent kinase (CDK) 2, and CDK4, in a dose-dependent manner. BMI1 overexpression diminished the inhibitory effect of DSF/copper in the thyrosphere formation of DTC cells. BMI1 knockdown by RNA interference in DTC cells also suppressed the self-renewal capability. DSF/copper could inhibit the nuclear localization and transcriptional activity of c-Myc and the binding of E2F1 to the BMI1 promoter. Overexpression of c-Myc or E2F1 further abolished the inhibitory effect of DSF/copper on BMI1 expression, suggesting that the suppression of c-Myc and E2F1 by DSF/copper was involved in the downregulation of BMI1 expression. In conclusion, DSF/copper targets CSCs in DTCs by inhibiting c-Myc- or E2F1-mediated BMI1 expression. Therefore, DSF is a potential therapeutic agent for future therapy in DTCs.

The Effects of Whole-Body Vibration Exercise Combined With an Isocaloric High-Fructose Diet on Osteoporosis and Immunomodulation in Ovariectomized Mice.

Background: Osteoporosis and immune-associated disorders are highly prevalent among menopausal women, and diet control and exercise exert beneficial effects on physiological modulation in this population. A controlled diet with a low fat content and a balanced caloric intake improves menopausal health, but the health effects of excessive fructose consumption on menopausal women are yet to be confirmed. In addition, whole-body vibration (WBV), a safe passive-training method, has been shown to have multiple beneficial effects on metabolism regulation, obesity, and bone health. Methods: The ovariectomized (OVX) C57BL/6J model was used to verify the effects of WBV combined with a high-fructose diet (HFrD) for 16 weeks on physiological modulation and immune responses. The mice were randomly allocated to sham, OVX, OVX+HFrD, and OVX+HFrD+WBV groups, which were administered with the indicated ovariectomy, dietary and WBV training treatments. We conducted growth, dietary intake, glucose homeostasis, body composition, immunity, inflammation, histopathology, and osteoporotic assessments (primary outcomes). Results: Our results showed that the isocaloric HFrD in OVX mice negated estrogen-deficiency-associated obesity, but that risk factors such as total cholesterol, glucose intolerance, osteoporosis, and liver steatosis still contributed to the development of metabolic diseases. Immune homeostasis in the OVX mice was also negatively affected by the HFrD diet, via the comprehensive stimulation of T cell activation, causing inflammation. The WBV intervention combined with the HFrD model significantly ameliorated weight gain, glucose intolerance, total cholesterol, and inflammatory cytokines (interferon gamma [IFN-γ], interleukin [IL]-17, and IL-4) in the OVX mice, although osteoporosis and liver steatosis were not affected compared to the negative control group. These findings indicate that an isocaloric high-fructose diet alone may not result in menopausal obesity, but that some deleterious physiological impacts still exist. Conclusion: The WBV method may modulate the physiological impacts of menopause and the HFrD diet, and should be considered as an alternative exercise prescription for people with poor compliance or who are unable or unwilling to use traditional methods to improve their health. In future studies, using the WBV method as a preventive or therapeutic strategy, combined with nutritional interventions, medication, and other exercise prescriptions, may prove beneficial for maintaining health in menopausal women.

Comparison of Sb2O3 and Sb2O3/SiO2 Double Stacked pH Sensing Membrane Applied in Electrolyte-Insulator-Semiconductor Structure.

In this study, electrolyte-insulator-semiconductor (EIS) capacitors with Sb2O3/SiO2 double stacked sensing membranes were fabricated with pH sensing capability. The results indicate that Sb2O3/SiO2 double stacked membranes with appropriate annealing had better material quality and sensing performance than Sb2O3 membranes did. To investigate the influence of double stack and annealing, multiple material characterizations and sensing measurements on membranes including of X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), and scanning electron microscopy (SEM) were conducted. These analyses indicate that double stack could enhance crystallization and grainization, which reinforced the surface sites on the membrane. Therefore, the sensing capability could be enhanced, Sb2O3/SiO2-based with appropriate annealing show promises for future industrial ion sensing devices.

Influence of Y Doping on WO3 Membranes Applied in Electrolyte-Insulator-Semiconductor Structures.

In this paper, tungsten oxide (WO3) is deposited on a silicon substrate applied in electrolyte-insulator-semiconductor structures for pH sensing devices. To boost the sensing performance, yttrium (Y) is doped into WO3 membranes, and annealing is incorporated in the fabrication process. To investigate the effects of Y doping and annealing, multiple material characterizations including X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), atom force microscopy (AFM), scanning electron microscopy (SEM), and transmission electron microscopy (TEM) are performed. Material analysis results indicate that annealing and Y doping can increase crystallinity, suppress defects, and enhance grainization, thereby strengthening membrane sensing capabilities in terms of sensitivity, linearity, and reliability. Because of their stable response, high reliability, and compact size, Y-doped WO3 membranes are promising for future biomedical applications.

Comparison of NH3 and N2O Plasma Treatments on Bi2O3 Sensing Membranes Applied in an Electrolyte-Insulator-Semiconductor Structure.

In this study, bismuth trioxide (Bi2O3) membranes in an electrolyte-insulator-semiconductor (EIS) structure were fabricated with pH sensing capability. To optimize the sensing performance, the membranes were treated with two types of plasma-NH3 and N2O. To investigate the material property improvements, multiple material characterizations were conducted. Material analysis results indicate that plasma treatments with appropriate time could enhance the crystallization, remove the silicate and facilitate crystallizations. Owing to the material optimizations, the pH sensing capability could be greatly boosted. NH3 or N2O plasma treated-Bi2O3 membranes could reach the pH sensitivity around 60 mV/pH and show promise for future biomedical applications.

Shikonin Induced Program Cell Death through Generation of Reactive Oxygen Species in Renal Cancer Cells.

Shikonin mitigated tumor cell proliferation by elevating reactive oxygen species (ROS) levels. Herein, we investigated the effects of shikonin on renal cancer cell (RCC) cell proliferation. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay indicated that shikonin dose-dependently reduced the proliferation of Caki-1 and ACHN cells. Shikonin remarkably triggered necrosis and apoptosis in Caki-1 and ACHN cells in proportion to its concentration. Moreover, necrostatin-1 recovered cell viability in the presence of shikonin. Elevated ROS levels and mitochondrial dysfunction were also found in shikonin treatment groups. Pretreatment with N-acetyl cysteine remarkably mitigated shikonin-induced cell death and ROS generation. Western blot analysis revealed that shikonin reduced pro-PARP, pro-caspase-3, and Bcl-2 expression and increased cleavage PARP expression. Enhanced autophagy was also found in the shikonin-treated group as evidenced by acridine orange staining. Moreover, light chain 3B (LC3B)-II accumulation and enhanced p62 expression indicated that autophagy occurred in the shikonin-treated group. LC3B knockdown considerably recovered cell viability in the presence of shikonin. Shikonin treatment elevated p38 activity in a dose-dependent manner. In conclusion, our results revealed that shikonin triggered programmed cell death via the elevation of ROS level and p38 activity in different types of RCC cells. These findings suggested that shikonin may be a potential anti-RCC agent.

The Ginsenoside Rg1 Rescues Mitochondrial Disorders in Aristolochic Acid-Induced Nephropathic Mice.

Chronic exposure to aristolochic acid (AA) leads to renal interstitial fibrosis and nephropathy. In this study, we aimed to investigate the renoprotective effects of Panax ginseng extract (GE) and ginsenoside saponin (GS) on AA-induced nephropathy (AAN) in mice. Eighty female C3H/He mice were randomly divided into eight groups, including normal; AA (3 µg/mL for 56 days); AA with GE (125, 250, or 500 mg/kg/d for 14 days); and AA with important GE ingredients, Rg1, Rb1, or Rd (5 mg/kg/d for 14 days). Compared with the AA group, renal injuries were significantly decreased in the GE (250 mg/kg/d), Rb1, and Rg1 treatment groups. Rg1 exhibited the best renoprotection among all GS-treated groups. There were 24 peaks significantly altered among normal, AA, and AA + Rg1 groups, and four mitochondrial proteins were identified, including acyl-CoA synthetase medium-chain family member 2, upregulated during skeletal muscle growth 5 (Usmg5), mitochondrial aconitase 2 (ACO2), and cytochrome c oxidase subunit Va preprotein (COX5a). We demonstrated for the first time that the AAN mechanism and renoprotective effects of Rg1 are associated with expression of mitochondrial proteins, especially ACO2, Usmg5, and COX5a.

Nerolidol inhibits proliferation of leiomyoma cells via reactive oxygen species-induced DNA damage and downregulation of the ATM/Akt pathway.

Nerolidol (3,7,11-trimethyl-1,6,10-dodecatrien-3-ol), a sesquiterpene alcohol present in aromatic essential oils of numerous plants, has been reported to possess anticancer activity. The potential therapeutic effect of nerolidol on uterine fibroids (UF), the most common benign tumor of the uterus worldwide, is unknown. In this study, we examined the anti-UF potential of nerolidol in ELT3 cells, a rat leiomyoma cell line widely used as an in vitro model, to identify the potential therapeutic agents for UF. We observed that treatment with cis- or trans-nerolidol inhibited cell proliferation in a dose-dependent manner and induced cell cycle arrest in the G1 phase, which was accompanied by reduction in Akt phosphorylation and downregulation of cyclin D1, cyclin-dependent kinase 4 (CDK4), and CDK6 protein expression. The proliferation-inhibiting activity of nerolidol correlated with the generation of intracellular reactive oxygen species (ROS), which was suppressed by N-acetyl-l-cysteine, a ROS inhibitor. Nerolidol treatment also increased the percentage of cells for which tail moment could be calculated using an alkaline comet assay, and induced p-γH2AXser139 expression, which indicated induction of DNA damage. We also observed downregulation of ATM and its phosphorylation after nerolidol treatment; furthermore, treatment with KU-55933, an ATM kinase inhibitor, mimicked the inhibitory effects of nerolidol treatment on cell proliferation and Akt phosphorylation. In conclusion, nerolidol displayed anti-UF activity in a leiomyoma cell model via ROS-induced DNA damage and G1 phase cell cycle arrest by inhibiting the expression and activation of the ATM/Akt pathway. Our data suggests that nerolidol is a potential therapeutic agent for UF.

Effects of various statins on depressive symptoms: A network meta-analysis.

BACKGROUND: Previous studies have indicated that statins can reduce the severity of depressive symptoms. However, the optimal choice of statin remains unclear. Therefore, we conducted a network meta-analysis to determine the optimal statin for treating depression. METHOD: We performed a pairwise and network meta-analysis by searching the PubMed, Embase, and Cochrane Library databases on October 29th, 2020. Eligible studies were randomized controlled trials that reported on changes in depressive symptoms. The Cochrane Collaboration tool was used to assess risk of bias. We tested for possible inconsistency globally by using a χ2-test and locally by calculating inconsistency factors for each comparison in closed loops. The ranking probabilities of being at each possible rank for each intervention were estimated. Comparison-adjusted funnel plots were obtained to assess publication bias. Sensitivity analysis was also performed. RESULTS: We identified 13 studies that matched our inclusion criteria. The risks of bias were mostly low. None of the global or local tests found significance. Compared with placebo, atorvastatin significantly reduced the severity of depressive symptoms (mean difference -3.46, 95% confidence interval -5.26 to -1.67). Atorvastatin had the first and second rank with probabilities of 44.9% and 39.0%, respectively. Comparison-adjusted funnel plots revealed no significant publication bias. LIMITATIONS: Low similarity of included studies and a relative large treatment effect of a single study were observed. CONCLUSIONS: In this first network meta-analysis, atorvastatin, with high intensity and a lipophilic effect, was identified as the optimal choice of statin for treating depression.

Application of Artificial Intelligence in the Establishment of an Association Model between Metabolic Syndrome, TCM Constitution, and the Guidance of Medicated Diet Care.

BACKGROUND: This study conducted exploratory research using artificial intelligence methods. The main purpose of this study is to establish an association model between metabolic syndrome and the TCM (traditional Chinese medicine) constitution using the characteristics of individual physical examination data and to provide guidance for medicated diet care. METHODS: Basic demographic and laboratory data were collected from a regional hospital health examination database in northern Taiwan, and artificial intelligence algorithms, such as logistic regression, Bayesian network, and decision tree, were used to analyze and construct the association model between metabolic syndrome and the TCM constitution. Findings. It was found that the phlegm-dampness constitution (90.6%) accounts for the majority of TCM constitution classifications with a high risk of metabolic syndrome, and high cholesterol, blood glucose, and waist circumference were statistically significantly correlated with the phlegm-dampness constitution. This study also found that the age of patients with metabolic syndrome has been advanced, and shift work is one of the risk indicators. Therefore, based on the association model between metabolic syndrome and TCM constitution, in the future, metabolic syndrome can be predicted through the syndrome differentiation of the TCM constitution, and relevant medicated diet care schemes can be recommended for improvement. CONCLUSION: In order to increase the public's knowledge and methods for mitigating metabolic syndrome, in the future, nursing staff can provide nonprescription medicated diet-related nursing guidance information via the prediction and assessment of the TCM constitution.

Evaluation of the nephrotoxicity and safety of low-dose aristolochic acid, extending to the use of Xixin (Asurum), by determination of methylglyoxal and d-lactate.

ETHNOPHARMACOLOGICAL RELEVANCE: Most Aristolochiaceae plants are prohibited due to aristolochic acid nephropathy (AAN), except Xixin (Asarum spp.). Xixin contains trace amounts of aristolochic acid (AA) and is widely used in Traditional Chinese Medicine. Methylglyoxal and d-lactate are regarded as biomarkers for nephrotoxicity. AIM OF THE STUDY: The use of Xixin (Asarum spp.) is essential and controversial. This study aimed to evaluate tubulointerstitial injury and interstitial renal fibrosis by determining urinary methylglyoxal and d-lactate after withdrawal of low-dose AA in a chronic mouse model. MATERIALS AND METHODS: C3H/He mice in the AA group (n = 24/group) were given ad libitum access to distilled water containing 3 µg/mL AA (0.5 mg/kg/day) for 56 days and drinking water from days 57 to 84. The severity of tubulointerstitial injury and fibrosis were evaluated using the tubulointerstitial histological score (TIHS) and Masson's trichrome staining. Urinary and serum methylglyoxal were determined by high-performance liquid chromatography (HPLC); urinary d-lactate were determined by column-switching HPLC. RESULTS: After AA withdrawal, serum methylglyoxal in the AA group increased from day 56 (429.4 ± 48.3 µg/L) to 84 (600.2 ± 99.9 µg/L), and peaked on day 70 (878.3 ± 171.8 µg/L; p < 0.05); TIHS and fibrosis exhibited similar patterns. Urinary methylglyoxal was high on day 56 (3.522 ± 1.061 µg), declined by day 70 (1.583 ± 0.437 µg) and increased by day 84 (2.390 ± 0.130 µg). Moreover, urinary d-lactate was elevated on day 56 (82.10 ± 18.80 µg) and higher from day 70 (201.10 ± 90.82 µg) to 84 (193.28 ± 61.32 µg). CONCLUSIONS: Methylglyoxal is induced after AA-induced tubulointerstitial injury, so methylglyoxal excretion and metabolism may be a detoxification and repair strategy. A low cumulative AA dose is the key factor that limits tubulointerstitial injury and helps to repair. Thus, AA-containing herbs, especially Xixin, should be used at low doses for short durations (less than one month).

Statin use and depression risk: A systematic review and meta-analysis.

BACKGROUND: Evidence regarding whether statin use is associated with depression is inconsistent. Therefore, we performed a meta-analysis to investigate this association. METHODS: We searched PubMed, the Cochrane Library, and the EMBASE database, limiting the search to human patients and articles written in English and published by March 31, 2020. The Newcastle-Ottawa scale for observational studies was used to assess study quality. All included studies were evaluated by 2 reviewers independently; any discrepancies were resolved through discussion. Because of the heterogeneity of study populations, a random effects model was used to calculate the pooled effect size. Statistical heterogeneity across studies was assessed using the I2 statistic. All analyses were performed using RevMan5 and Comprehensive Meta-Analysis software. RESULTS: A total of 13 observational (9 cohort, 3 case-control, and 1 cross-sectional) studies conducted in 11 countries and enrolling 5 035 070 participants were included. Substantial statistical heterogeneity was discovered (I2, 83%). Overall, use of statins was not associated with depression after trim and fill analysis (adjusted pooled odds ratio [OR], 0.87; 95% CI, 0.74-1.02). The finding was consistent in the subgroup analysis, except for studies published before 2013, showing statin use was associated with a lower risk of depression. LIMITATIONS: High heterogeneity and asymmetry funnel plot of ORs from these studies were observed. CONCLUSIONS: This meta-analysis revealed statin use was not associated with depression. However, high heterogeneity was observed between identified studies, and results were inconsistent in the subgroups of studies published before 2013.

Comparison of Magnesium and Titanium Doping on Material Properties and pH Sensing Performance on Sb2O3 Membranes in Electrolyte-Insulator-Semiconductor Structure.

In this research, electrolyte-insulator-semiconductor (EIS) capacitors with Sb2O3 sensing membranes were fabricated. The results indicate that Mg doping and Ti-doped Sb2O3 membranes with appropriate annealing had improved material quality and sensing performance. Multiple material characterizations and sensing measurements of Mg-doped and Ti doping on Sb2O3 sensing membranes were conducted, including of X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS) and transmission electron microscopy (TEM). These detailed studies indicate that silicate and defects in the membrane could be suppressed by doping and annealing. Moreover, compactness enhancement, crystallization and grainization, which reinforced the surface sites on the membrane and boosted the sensing factor, could be achieved by doping and annealing. Among all of the samples, Mg doped membrane with annealing at 400 °C had the most preferable material properties and sensing behaviors. Mg-doped Sb2O3-based with appropriate annealing are promising for future industrial ionsensing devices and for possible integration with Sb2O3-based semiconductor devices.

Utilizing methylglyoxal and D-lactate in urine to evaluate saikosaponin C treatment in mice with accelerated nephrotoxic serum nephritis.

The relationship between methylglyoxal (MGO) and D-lactate during saikosaponin C (SSC) treatment of mice with accelerated nephrotoxic serum (NTS) nephritis was investigated. NTS nephritis was induced by administration of anti-basement membrane antibodies to C57BL/6 mice and three dosages of SSC were administered for 14 days. Proteinuria, blood urea nitrogen, serum creatinine, renal histology, urinary MGO and d-lactate changes were examined. Compared to the NTS control group, the middle dosage (10 mg/kg/day) of SSC significantly alleviated the development of nephritis based on urine protein measurements (34.40 ± 6.85 vs. 17.33 ± 4.79 mg/day, p<0.05). Pathological observation of the glomerular basement membrane (GBM) revealed monocyte infiltration, hypertrophy, and crescents were alleviated, and injury scoring also showed improved efficacy for the middle dose of SSC during nephritis (7.92 ± 1.37 vs. 3.50 ± 1.14, p<0.05). Moreover, the significant decreases in urinary levels of MGO (24.71 ± 3.46 vs. 16.72 ± 2.36 µg/mg, p<0.05) and D-lactate (0.31 ± 0.04 vs. 0.23 ± 0.02 µmol/mg, p<0.05) were consistent with the biochemical and pathological examinations. This study demonstrates that MGO and D-lactate may reflect the extent of damage and the efficacy of SSC in NTS nephritis; further studies are required to enable clinical application.

Methylglyoxal and D-lactate in cisplatin-induced acute kidney injury: Investigation of the potential mechanism via fluorogenic derivatization liquid chromatography-tandem mass spectrometry (FD-LC-MS/MS) proteomic analysis.

Nephrotoxicity severely limits the chemotherapeutic efficacy of cisplatin (CDDP). Oxidative stress is associated with CDDP-induced acute kidney injury (AKI). Methylglyoxal (MG) forms advanced glycation end products that elevate oxidative stress. We aimed to explore the role of MG and its metabolite D-lactate and identify the proteins involved in CDDP-induced AKI. Six-week-old female BALB/c mice were intraperitoneally administered CDDP (5 mg/kg/day) for 3 or 5 days. Blood urea nitrogen (42.6 ± 7.4 vs. 18.3 ± 2.5; p < 0.05) and urinary N-acetyl-ß-D-glucosaminide (NAG; 4.89 ± 0.61 vs. 2.43 ± 0.31 U/L; p < 0.05) were significantly elevated in the CDDP 5-day group compared to control mice. Histological analysis confirmed AKI was successfully induced. Confocal microscopy revealed TNF-α was significantly increased in the CDDP 5-day group. Fluorogenic derivatized liquid chromatography-tandem mass spectrometry (FD-LC-MS/MS) showed the kidney MG (36.25 ± 1.68 vs. 18.95 ± 2.24 mg/g protein, p < 0.05) and D-lactate (1.78 ± 0.29 vs. 1.12 ± 0.06 mol/g protein, p < 0.05) contents were significantly higher in the CDDP 5-day group than control group. FD-LC-MS/MS proteomics identified 33 and nine altered peaks in the CDDP 3-day group and CDDP 5-day group (vs. control group); of the 35 proteins identified using the MOSCOT database, 11 were antioxidant-related. Western blotting confirmed that superoxide dismutase 1 (SOD-1) and parkinson disease protein 7 (DJ-1) are upregulated and may participate with MG in CDDP-induced AKI. This study demonstrates TNF-α, MG, SOD-1 and DJ-1 play crucial roles in CDDP-induced AKI.