Diabetic nephropathy (DN) is the one of the leading causes of end-stage renal disease (ESRD) in clinical. However, it is still lack of accurate biomarkers and effective methods for diagnosing and ...curing DN. Therefore, there is an urgent need to develop a definite strategy for the identification of reliable and versatile biomarkers for risk assessment of DN and search for therapeutic approaches that can effectively attenuate DN progression. Treatment with Gandi capsule (GDC) not only decreased the levels of urinary albumin excretion, but also increased the levels of estimated glomerular filtration rate (eGFR), indicating that it produces a renal protective effect on diabetic nephropathy. Based on metabolomics investigation including UHPLC–MS analysis and multivariate statistical analysis, sixteen disordered metabolites were screened out and considered as potential biomarkers corresponding to DN, which were mostly improved and partially returned to normalcy in GDC treatment group. Therefore, it was suggested that GDC was a promising therapeutic agent against DN. The underlying mechanisms of GDC attenuating the development of DN may be improving abnormal metabolic disorders by retrieving the imbalance of glycine metabolism, tryptophan metabolism, valine, leucine and isoleucine degradation, purine metabolism, nitrotoluene degradation, phenylalanine metabolism, fatty acid metabolism, tyrosine metabolism and bile acid metabolism pathways. The data obtained in this study may provide key clues to enhance our understanding of the metabolic mechanism of DN and shed new insights into the therapeutic mechanism of GDC.
•Metabolomics was used to analyze urine metabolites in diabetic nephropathy patients.•We identified sixteen disordered biomarkers corresponding to diabetic nephropathy.•Gandi capsule can attenuate the development of DN by improving abnormal metabolic disorders.
Although the deep galleries of natural underground cavities are difficult to access and are sometimes dangerous, they have the potential to preserve trace fossils. Here, we report on the first ...occurrence of sauropod dinosaur tracks inside a karstic cave. Three trackways are preserved on the roof of the Castelbouc cave 500 m under the surface of the Causse Méjean plateau, southern France. The tracks are Bathonian in age (ca. 168–166 Ma), a crucial but still poorly known time interval in sauropod evolution. The three trackways yield sauropod tracks that are up to 1.25 m long and are therefore amongst the largest known dinosaur footprints worldwide. The trackmakers are hypothesized to be titanosauriforms. Some of the tracks are extremely well preserved and show impressions of digits, digital pads, and claws. We erect the new ichnogenus and ichnospecies Occitanopodus gandi, igen. et isp. nov. In order to characterize depositional environments, we conducted sedimentological, petrographic, and mineralogical analyses. The tracks from Castelbouc attest the presence of sauropods in proximal littoral environments during the Middle Jurassic. This discovery demonstrates the great potential of prospecting in deep karst caves that can occasionally offer larger and better-preserved surfaces than outdoor outcrops.
Gandi capsule (GDC) has been used clinically for years for treatment of vascular lesions caused by diabetes. However, its comprehensive ingredients, especially those that can be absorbed, remain ...unclear. In this study, we developed a simple and fast ultra-high performance liquid chromatography–quadrupole time-of-flight mass spectrometry (UHPLC–Q-TOFMS) method to identify the ingredients of GDC extract, as well as those that can permeate the Caco-2 monolayer cell model. Firstly, 52 components were rapidly identified in GDC extract. Then, a total of 17 components were able to pass across Caco-2 cells from the apical side to the basolateral side with the apparent permeability coefficients (
P
app
) > 1.0 × 10
−5
cm/s, which indicate good intestinal permeability and bioavailability. Furthermore, 14 of the 17 penetrative components were definitely detected and identified in rat plasma. These results confirmed that the combination of Caco-2 monolayer cell absorption model and UHPLC–Q-TOFMS is suitable for fast screening of the ingredients entering the blood circulation. Our results will serve as a foundation for further evaluation of the pharmacological efficacy of GDC in the clinical treatment of diabetic vascular disease.
Graphical abstract
Background Gandi capsule is a traditional Chinese herbal formula used to promote blood circulation and removing blood stasis in clinical. Our previous study has shown that it reduces proteinuria with ...routine treatment in diabetic nephrophy (DN), but its pharmacological action mechanism is still unknown. Methods To facilitate the identification of components, a component database of Gandi capsule and target database of DN were established by ourselves. The components absorbed in blood circle were identified in rat plasma after oral administration of Gandi capsule by UHPLC-QQQ-MS/MS. The potential targets were screened by using Libdock tolls in Discovery studio 3.0. Then Pathway and Network analyses were used to enrich the screened targets. The possible targets were verified by using a surface plasmon resonance (SPR) test and the molecular mechanism focusing these targets for treating DN was clarified by western blot. Results Six components in Gandi capsule were identified detected in rat plasma after oral administration by UHPLC-QQQ-MS/MS. After molecular docking analyses in KEGG and Discovery studio, four protein targets including HNF4A, HMGCR, JAK3, and SIRT1, were screened out, and proved as effective binding with baicalin, wogonoside by SPR. And the molecular mechanism was clarified that baicalin and wogonoside inhibit the effect of high glucose (HG)-induced decreased cell viability and podocin expression, and strengthen the activation p-AKT, p-PI3K, and p-AMPK. Conclusion Baicalin and wogonoside were screened out to be the active compounds in Gandi capsule and can ameliorate HG-induced podocyte damage by influencing the AMPK and PI3K-AKT signaling pathways by binding with HNF4A, HMGCR, JAK3, and SIRT1. Graphical abstract Keywords: Gandi capsule, Network pharmacology; active component UHPLC-QQQ-MS/MS, Surface plasmon resonance, Molecular mechanism; action target
Apart of Mrs T. Gandi, the delegation comprises Ch. Altankhuyag, head of the General Authority for Social Insurance (GASI); G. Bilegsaikhan, director of the Centre of Sending Labour Force to Abroad; ...and other officials. They will meet Mongolians living in the South Korea, to hear their onions and to get au fait with life of them.
Recent archaeological investigations of the Gomal plain in northwestern Pakistan have revealed important new evidence for the types of regional socio-economic transformations that were taking place ...in the lead up to the development of urban centres on the Indus plain in the third millennium BC. It is now clear that there were several early phases of cultural development in the region, and excavations at the site of Gandi Umar Khan have revealed evidence for a previously unknown transition, between the 'Tochi-Gomal' and 'Kot Diji' phases. This article will present the evidence for this transition and investigate its broader cultural context.
Türk devriminin I. Dünya Savaşı ertesinde anti-emperyalist bir karakterde gerçekleştirilmiş olması,
devrimin ve devrim sonrasında gerçekleştirilen inkılâpların evrensel manada emsal teşkil etmesini
...de beraberinde getirmiştir. Hint ve İran devrimleri, Türk devrimiyle çağdaş olmamalarına rağmen, Türk devriminin sömürgeci güçlere karşı verdiği mücadeleden ve bu mücadeleler sonrası gerçekleştirilen inkılâplardan etkilenmişlerdir. Ancak her iki devrimin de Türk devrimi ile birebir örtüştüğünü söylemek güçtür. Nitekim her bir devrim, içinden çıktığı toplumunun sosyo-ekonomik ve siyasal yapısına uygun olarak, kendine özgü nitelikler taşımaktadır. Bu makalenin amacı da Türk devriminin Hint ve İran devrimleri üzerindeki etkisini bu devrimlerin kendine özgü niteliklerini de hesaba katarak analiz etmektir.
The SPLM-DC Secretary General condemns the continued arrest, harassment and torture of members of the registered party SPLM-DC in Southern Sudan. The SPLM-DC is now a party with members in ...Parliament; be it in Juba or the Southern states or in the National Assembly and this despite all the Elections ringing which went on in the Southern Sudan which clearly shows the overwhelming support of the masses in Southern Sudan for SPLM-DC which still guaranteed SPLM-DC some victory despite rigging. Hence the authorities in southern should adhere really to democratic principle rather the making a show to the world when they claim to swear in leaders from elections while at the same time continues to harass, torture and intimidate opposition parties like the SPLM-DC. Opposition is a healthy idea for all governments around the world.
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