Fibroblast growth factor 2 protects against renal ischaemia/reperfusion injury by attenuating mitochondrial damage and proinflammatory signalling.

Ischaemia-reperfusion injury (I/RI) is a common cause of acute kidney injury (AKI). The molecular basis underlying I/RI-induced renal pathogenesis and measures to prevent or reverse this pathologic process remains to be resolved. Basic fibroblast growth factor (FGF2) is reported to have protective roles of myocardial infarction as well as in several other I/R related disorders. Herein we present evidence that FGF2 exhibits robust protective effect against renal histological and functional damages in a rat I/RI model. FGF2 treatment greatly alleviated I/R-induced acute renal dysfunction and largely blunted I/R-induced elevation in serum creatinine and blood urea nitrogen, and also the number of TUNEL-positive tubular cells in the kidney. Mechanistically, FGF2 substantially ameliorated renal I/RI by mitigating several mitochondria damaging parameters including pro-apoptotic alteration of Bcl2/Bax expression, caspase-3 activation, loss of mitochondrial membrane potential and KATP channel integrity. Of note, the protective effect of FGF2 was significantly compromised by the KATP channel blocker 5-HD. Interestingly, I/RI alone resulted in mild activation of FGFR, whereas FGF2 treatment led to more robust receptor activation. More significantly, post-I/RI administration of FGF2 also exhibited robust protection against I/RI by reducing cell apoptosis, inhibiting the release of damage-associated molecular pattern molecule HMBG1 and activation of its downstream inflammatory cytokines such as IL-1α, IL-6 and TNF α. Taken together, our data suggest that FGF2 offers effective protection against I/RI and improves animal survival by attenuating mitochondrial damage and HMGB1-mediated inflammatory response. Therefore, FGF2 has the potential to be used for the prevention and treatment of I/RI-induced AKI.

A network pharmacology approach to understanding the mechanisms of action of traditional medicine: Bushenhuoxue formula for treatment of chronic kidney disease.

Traditional Chinese medicine (TCM) has unique therapeutic effects for complex chronic diseases. However, for the lack of an effective systematic approach, the research progress on the effective substances and pharmacological mechanism of action has been very slow. In this paper, by incorporating network biology, bioinformatics and chemoinformatics methods, an integrated approach was proposed to systematically investigate and explain the pharmacological mechanism of action and effective substances of TCM. This approach includes the following main steps: First, based on the known drug targets, network biology was used to screen out putative drug targets; Second, the molecular docking method was used to calculate whether the molecules from TCM and drug targets related to chronic kidney diseases (CKD) interact or not; Third, according to the result of molecular docking, natural product-target network, main component-target network and compound-target network were constructed; Finally, through analysis of network characteristics and literature mining, potential effective multi-components and their synergistic mechanism were putatively identified and uncovered. Bu-shen-Huo-xue formula (BSHX) which was frequently used for treating CKD, was used as the case to demonstrate reliability of our proposed approach. The results show that BSHX has the therapeutic effect by using multi-channel network regulation, such as regulating the coagulation and fibrinolytic balance, and the expression of inflammatory factors, inhibiting abnormal ECM accumulation. Tanshinone IIA, rhein, curcumin, calycosin and quercetin may be potential effective ingredients of BSHX. This research shows that the integration approach can be an effective means for discovering active substances and revealing their pharmacological mechanisms of TCM.

Synthesis, anti-tumor activity, and structure-activity relationships of curcumol derivatives.

Using curcumol that was extracted from the volatile oil of Rhizoma Curcumae as the raw material, its derivatives were synthesized and purified. The structures of these compounds were confirmed by (1)H, (13)C NMR, and mass spectral data. The test compounds were evaluated for their in vitro anti-tumor activity against gastric cancer cell lines SGC-7901 and lung carcinoma cell line H460 by methyl thiazolyl tetrazolium chromatometry. Distinct structure-activity relationships of these curcumol derivatives were also revealed for inhibiting cell proliferation. Presence of electron-withdrawing groups or amino could increase the activity significantly, whereas esterification of 8-hydroxy diminished the anti-tumor activity. Many of the tested candidates exhibited higher inhibition efficiency than curcumol, suggesting that structural modifications could enhance its activity effectively.

Metabolic changes detected by ex vivo high resolution 1H NMR spectroscopy in the striatum of 6-OHDA-induced Parkinson's rat.

Parkinson's disease (PD) is a neurodegenerative disorder characterized by the progressive loss of the dopaminergic neurons; however, its crucial mechanism of the metabolic changes of neurotransmitters remains ambiguous. The pathological mechanism of PD might involve cerebral metabolism perturbations. In this study, ex vivo proton nuclear magnetic resonance ((1)H NMR) was used to determine the level changes of 13 metabolites in the bilateral striatum of 6-hydroxydopamine (6-OHDA)-induced PD rats. The results showed that, in the right striatum of 6-OHDA-induced PD rats, increased levels of glutamate (Glu) and γ-aminobutyric acid (GABA) concomitantly with decreased level of glutamine (Gln) were observed compared to the control. Whereas, in the left striatum of 6-OHDA-induced PD rats, increased level of Glu with decreased level of GABA and unchanged Gln were observed. Other cerebral metabolites including lactate, alanine, creatine, succinate, taurine, and glycine were also found to have some perturbations. The observed metabolic changes for Glu, Gln, and GABA are mostly likely the result of a shift in the steady-state equilibrium of the Gln-Glu-GABA metabolic cycle between astrocytes and neurons. The altered Gln and GABA levels are most likely as a strategy to protect neurons from Glu excitotoxic injury after striatal dopamine depletion. Changes in energy metabolism and tricarboxylic acid cycle might be involved in the pathogenesis of PD.

[Synthesis and antibacterial activity of ciprofloxacin derivatives].

AIM: To study the synthesis and antibacterial activity of ciprofloxacin derivatives. METHODS: Ciprofloxacin derivatives were synthesized primarily from 2-methyl-5-nitroimidazol and ciprofloxacin through nucleophilic substitution. The antibacterial activity of the synthesized compounds were tested. RESULTS: Nine new compounds were synthesized. The structure of the title compounds were confirmed by 1H NMR, MS and element analysis. CONCLUSION: Compounds II, IVC and IVD showed appreciable antibacterial activity, and were worth further studying.

[Synthesis and antibacterial activity of pyridonecarboxylic acid derivatives containing 2-methyl-5-nitroimidazol].

AIM: To study the synthesis and antibacterial activity of pyridonecarboxylic acid derivatives containing 2-methyl-5-nitroimidazol. METHODS: Pyridonecarboxylic acid derivatives containing 2-methyl-5-nitroimidazol were synthesized primarily from 2-methyl-5-nitroimidazol, norfloxacin, ciprofloxacin, enoxacin via nucleophilic substitution and esterification. The antibacterial activity of the nine target compounds were tested. RESULTS: Nine new compounds were synthesized (IIa-c and IIIa-f). The structure of the title compounds were identified by 1HNMR, MS as well as elementary analysis. CONCLUSION: Compounds IIa, IIb and IIc showed antibacterial activity, and were worth further studying.