Circulating galectin-3 level association with cardiovascular risk factors during peritoneal dialysis.

OBJECTIVE: Cardiovascular disease (CVD) represents the primary cause of mortality in patients afflicted with end-stage renal disease and undergoing peritoneal dialysis (PD) treatment. Galectin-3 (Gal-3), a molecule known to exhibit a correlation with CVD mortality garners considerable interest. The objective of this study was to explore the potential association between serum Gal-3 levels and other CVD risk factors among PD patients. METHODS: In this cross-sectional study, a total of 114 PD patients with a minimum of 3 months of PD treatment were enrolled. Serum Gal-3 levels were quantified using an enzyme-linked immunosorbent assay. The data of patients with Gal-3 levels higher and lower than 26.744 pg/ml were compared using Mann-Whitney U tests or t tests. Pearson's correlation or Spearman's correlation analysis and multivariate regression were used to assess the associations between the known risk factors for CVD and Gal-3. RESULTS: In comparison to the inter-group baseline data, the low Gal-3 group exhibited a higher glomerular filtration rate (GFR). Gal-3 levels correlate positively with PD duration, B-type natriuretic peptide (BNP), growth differentiation factor 15 (GDF-15), interventricular septal thickness in diastolic (IVST), and left ventricular mass index (LVMI). Conversely, Gal-3 exhibited a negative correlation with albumin levels. Multivariate linear regression analysis demonstrated a positive correlation between Gal-3 levels and BNP, GDF-15, PD duration, IVST and LVMI. Gal-3 levels were negatively correlated with albumin levels. CONCLUSIONS: Gal-3 was strongly associated with BNP, GDF-15, IVST and LVMI in patients undergoing PD treatment. Prospective studies should be carried out to determine whether Gal-3 can be a promising biomarker in predicting increased risk of adverse cardiovascular events in PD patients.

Artemether ameliorates adriamycin induced cardiac atrophy in mice.

Adriamycin is a widely used and effective antitumor drug; however, its application is limited by various side effects, including irreversible cardiotoxicity. The central role of cardiac atrophy in Adriamycin­induced cardiotoxicity has been revealed; however, the underlying mechanism of this process remains unclear. Artemether is a well­known Chinese herbal medicine, and its pharmacological action is related to the regulation of mitochondrial function and redox status. The present study determined the effects of artemether on Adriamycin­induced cardiotoxicity and investigated the underlying mechanisms. After mouse model establishment and artemether intervention, experimental methods including pathological staining, immunohistochemistry, immunofluorescence, immunoblotting, ELISA and reverse transcription­quantitative PCR were used to evaluate the therapeutic effect. The results demonstrated that artemether prevented Adriamycin­induced cardiac atrophy and recovered the intercombination of connexin 43 and N­cadherin at the intercalated discs. Artemether also regulated the autophagy pathway and restored the unbalanced ratio of Bax and Bcl­2 in myocardial cells. In addition, the increased serum H2O2 levels after Adriamycin exposure were significantly decreased by artemether, and the mitochondrial alterations and redox imbalance in myocardial cells were also improved to varying degrees. In summary, the findings of the present study provide reliable evidence that artemether could ameliorate cardiac atrophy induced by Adriamycin. This therapeutic approach may be translated to the clinic for preventing drug­induced heart diseases.

Artemether attenuates renal tubular injury by targeting mitochondria in adriamycin nephropathy mice.

Chronic kidney disease (CKD) is complex and current treatment remains limited. As we know, glomerular injury plays a dominant role in kidney disease progression. However, accumulating evidence demonstrated that renal tubules, rather than being victims or bystanders, are major initiators in renal fibrosis progression. Renal tubules are rich in mitochondria and mitochondrial dysfunction may participate in renal tubular phenotypic changes and ultimately promote renal fibrosis. Previous studies have proved that artemether displayed renal protective effects, but the mechanisms remain unclear. In this experiment, we showed that artemether reduced urinary protein/creatinine ratio and attenuated renal tubular injury. Both in vivo and in vitro results indicated that artemether could restore renal tubular phenotypic alterations. Meanwhile, the unbalanced expressions of Bax and Bcl-xL in renal tubules were restored by artemether. In addition, artemether also regulated mitochondrial pyruvate metabolism, increased mitochondrial biogenesis, and improved mitochondrial function. Taken together, this study suggested that artemether could attenuate renal tubular injury by regulating mitochondrial biogenesis and function. It has great potential to be translated to the clinic as a therapeutic agent for treating kidney diseases, especially those associated with renal tubular injury.

Artemether ameliorates kidney injury by restoring redox imbalance and improving mitochondrial function in Adriamycin nephropathy in mice.

The kidney is a high-energy demand organ rich in mitochondria especially renal tubular cells. Emerging evidence suggests that mitochondrial dysfunction, redox imbalance and kidney injury are interconnected. Artemether has biological effects by targeting mitochondria and exhibits potential therapeutic value for kidney disease. However, the underlying molecular mechanisms have not been fully elucidated. This study was performed to determine the effects of artemether on Adriamycin-induced nephropathy and the potential mechanisms were also investigated. In vivo, an Adriamycin nephropathy mouse model was established, and mice were treated with or without artemether for 2 weeks. In vitro, NRK-52E cells were stimulated with TGF-ß1 and treated with or without artemether for 24 h. Then renal damage and cell changes were evaluated. The results demonstrated that artemether reduced urinary protein excretion, recovered podocyte alterations, attenuated pathological changes and alleviated renal tubular injury. Artemether also downregulated TGF-ß1 mRNA expression levels, inhibited tubular proliferation, restored tubular cell phenotypes and suppressed proliferation-related signalling pathways. In addition, artemether restored renal redox imbalance, increased mtDNA copy number and improved mitochondrial function. In summary, we provided initial evidence that artemether ameliorates kidney injury by restoring redox imbalance and improving mitochondrial function in Adriamycin nephropathy in mice. Artemether may be a promising agent for the treatment kidney disease.

Astragaloside IV alleviates puromycin aminonucleoside-induced podocyte cytoskeleton injury through the Wnt/PCP pathway.

Podocyte injury is a common cause of massive proteinuria. Astragaloside IV (AS-IV) has been reported to protect podocytes in diabetic models. However, the effects and potential mechanism of AS-IV on puromycin aminonucleoside (PAN)-induced podocyte injury remains unclear. The aim of the present study was to investigate the protective effect of AS-IV on PAN-induced podocyte injury both in vivo and in vitro. In vivo, we induced a podocytic-injury model in rats via a single tail vein injection of PAN. The rats in the treatment group received AS-IV intragastrically (i.g.) at a dose of 40 mg/kg/day for 10 days. At the end of the experiment, 24 h urine, serum and kidney samples were collected for examination. In vitro, we injured podocytes with 30 µg/ml PAN and treated them with AS-IV at concentrations of 5, 25 and 50 µg/ml. Next, we analyzed podocyte protein expression and the Wnt/planar-cell polarity (PCP) pathway using western blot and immunofluorescence (IF). Our results showed that AS-IV decreased proteinuria in PAN-injured rats, and restored specific protein expression in podocytes. In PAN-induced injuries to human podocytes, AS-IV restored the expression and distribution of F-actin and synaptopodin, and repaired the morphology of the actin-based cytoskeleton. Notably, AS-IV could activate the Wnt/PCP pathway by promoting expression of Wnt5a, protein tyrosine kinase 7 (PTK7), Rho-associated coiled-coil-containing protein kinase 1 (ROCK1), Ras-related C3 botulinum toxin substrate 1 (Rac1) and phospho-SAPK/JNK (Thr183/Tyr185) (p-JNK) in vivo and in vitro. In conclusion, we demonstrated that AS-IV alleviated PAN-induced injury to the podocyte cytoskeleton, partially by activating the Wnt/PCP pathway.

Niclosamide ethanolamine protects kidney in adriamycin nephropathy by regulating mitochondrial redox balance.

Chronic kidney disease (CKD) is commonly characterized by proteinuria and leads to progressive glomerulosclerosis and tubulointerstitial fibrosis. Accumulating evidence implicates mitochondrial dysfunction including reactive oxygen species (ROS) overproduction in the pathogenesis of CKD. Mitochondrial function and ROS production are regulated by mitochondrial uncoupling. Niclosamide ethanolamine salt (NEN) is a mild mitochondrial uncoupler, which reduces urinary albumin excretion in mice with diabetic kidney disease. However, its role in nondiabetic kidney disease has not been investigated. Here we show that NEN exerts renoprotective effects in adriamycin induced nondiabetic kidney disease. It reduces urinary protein excretion, restores podocyte function, ameliorates renal pathological injury, and decreases the excretion of the urinary tubular injury biomarkers NGAL and Kim-1. Specifically, NEN uncouples isolated kidney mitochondria, and dose-dependently decreases the renal production and urinary excretion of H2O2. Moreover, NEN increases catalase and PGC-1α expression, which might accelerate H2O2 scavenging. The results of this study provide the first evidence that NEN protects kidney in nondiabetic kidney disease by regulating redox balance.

[Clinical observation on Jiquan (HT 1) for treatment of cervical spondylosis of nerve root type].

OBJECTIVE: To observe acupuncture at Jiquan (HT 1) with different manipulations for improvement of abnormal sensation of the upper limb induced by cervical spondylosis of nerve root type. METHODS: One hundred and seven cases were randomly divided into 3 groups. The lifting-thrusting group (n = 37) were treated with acupuncture at Jiquan (HT 1) with lifting-thrusting manipulation, the twirling group (n = 36) with acupuncture at Jiquan (HT 1) with twirling manipulation and the routine needling group (n = 34) with acupuncture at C4 - T1 Jiaji (EX-B 2), Quchi (LI 11). RESULTS: The total effective rate of 91.9% in the lifting-thrusting group was significantly better than 58.3% in the twirling group (P < 0.005) and 76.5% in the routine needling group (P < 0.05), and the therapeutic effect of the twirling group was similar to that in the routine needling group CP > 0.05). CONCLUSION: Acupuncture at Jiquan (HT 1) with lifting-thrusting manipulation can obviously improve abnormal sensation of the upper limb induced by cervical spondylosis of nerve root type.