Protective effect of paeoniflorin in diabetic nephropathy: A preclinical systematic review revealing the mechanism of action.

BACKGROUND: Paeoniflorin (PF), the main active glucoside of Paeonia Lactiflora, has many pharmacological activities, such as inhibition of vasodilation, hypoglycemia, and immunomodulation. Although the current evidence has suggested the therapeutic effects of PF on diabetic nephropathy (DN), its potential mechanism of action is still unclear. PURPOSE: A systematic review and meta-analysis of the existing literature on paeoniflorin treatment in DN animal models was performed to evaluate the efficacy and mechanism of PF in DN animal models. METHODS: The risk of bias in each study was judged using the CAMARADES 10-item quality checklist with the number of criteria met varying from 4 / 10 to 7 / 10, with an average of 5.44. From inception to July 2022, We searched eight databases. We used the Cochrane Collaboration's 10-item checklist and RevMan 5.3 software to assess the risk of bias and analyze the data. Three-dimensional dose/time-effect analyses were conducted to examine the dosage/time-response relations between PF and DN. RESULTS: Nine animal studies were systematically reviewed to evaluate the effectiveness of PF in improving animal models of DN. Meta-analysis data and intergroup comparisons indicated that PF slowed the index of mesangial expansion and tubulointerstitial injury, 24-h urinary protein excretion rate, expression of anti-inflammatory mediators (mRNA of MCP-1, TNF-α, iNOS, and IL-1 ß), and expression of immune downstream factors (P-IRAK1, TIRF, P-IRF3, MyD88, and NF-κBp-p65). Furthermore, modeling methods, animal species, treatment duration, thickness of tissue sections during the experiment, and experimental procedures were subjected to subgroup analyses. CONCLUSION: The present study demonstrated that the reno-protective effects of PF were associated with its inhibition on macrophage infiltration, reduction of inflammatory mediators, and immunomodulatory effects. In conclusion, PF can effectively slow down the progression of DN and hold promise as a protective drug for the treatment of DN. Due to the low bioavailability of PF, further studies on renal histology in animals are urgently needed. We therefore recommend an active exploration of the dose and therapeutic time frame of PF in the clinic and in animals. Moreover, it is suggested to actively explore methods to improve the bioavailability of PF to expand the application of PF in the clinic.

MicroRNA-26a and -26b inhibit lens fibrosis and cataract by negatively regulating Jagged-1/Notch signaling pathway.

This corrects the article DOI: 10.1038/cdd.2016.152.

MicroRNA-26a and -26b inhibit lens fibrosis and cataract by negatively regulating Jagged-1/Notch signaling pathway.

Fibrosis is a chronic process involving development and progression of multiple diseases in various organs and is responsible for almost half of all known deaths. Epithelial-mesenchymal transition (EMT) is the vital process in organ fibrosis. Lens is an elegant biological tool to investigate the fibrosis process because of its unique biological properties. Using gain- and loss-of-function assays, and different lens fibrosis models, here we demonstrated that microRNA (miR)-26a and miR-26b, members of the miR-26 family have key roles in EMT and fibrosis. They can significantly inhibit proliferation, migration, EMT of lens epithelial cells and lens fibrosis in vitro and in vivo. Interestingly, we revealed that the mechanisms of anti-EMT effects of miR-26a and -26b are via directly targeting Jagged-1 and suppressing Jagged-1/Notch signaling. Furthermore, we provided in vitro and in vivo evidence that Jagged-1/Notch signaling is activated in TGFß2-stimulated EMT, and blockade of Notch signaling can reverse lens epithelial cells (LECs) EMT and lens fibrosis. Given the general involvement of EMT in most fibrotic diseases, cancer metastasis and recurrence, miR-26 family and Notch pathway may have therapeutic uses in treating fibrotic diseases and cancers.

Characterization of novel nucleoside analogs by electrospray ionization mass spectra.

In this paper, we synthesized a novel nucleoside analog by coupling thymine with dimethyl dicarboxylate biphenyl (DDB). The structure of the target compound was determined using 1H nuclear magnetic resonance (NMR) and electrospray ionization tandem mass spectrometry (ESI-MS/MS). The fragmentation pathways were studied in details through ESI-MS/MS. By comparing with unsubstituted nucleosides, such as AZT, MCI, d4T and DDI, it was found that the nucleoside analog coupled with DDB would not yield the daughter ions corresponding to the fragments of the nucleoside base and arabinofuranose analogs, but would lose a neutral molecule HF and DDB easily. However, the unsubstituted nucleosides could lightly yield the fragment ions of the nucleoside base and sugar ring. Hence, electrospray ionization mass spectrometry combined with tandem mass spectrometry (MS/MS) provides a convenient method to recognize the substituted and unsubstituted nucleosides.

Stent-jail technique in endovascular treatment of wide-necked aneurysm.

AIM: To describe a reconstructive technique using single stent for wide-necked aneurysms. MATERIAL AND METHODS: This technique was described as stent-jail technique consisting of the aneurismal catheterization before the deployment of a self-expandable stent across the aneurysm neck. Following the deployment of the stent, embolization coils were delivered with the microcatheter positioned within the aneurysm dome and wedged between the stent and the aneurysm dome. The microstents, such as Neuroform, Leo and Wingspan stents, were used in in our series for electively treated aneurysms. RESULTS: During a 3-year period,13 patients with wide-necked aneurysms were treated electively with this technique. The aneurysms arose from the internal carotid artery (5), anterior cerebral artery (4), anterior communicating artery (1), vertebral artery ( 1), middle cerebral artery (1) and middle cerebral artery (1). Thirteen stents (6 Leo stents, 4 Neuroform stents and 3 Wingspan stents) were successfully deployed across the aneurysm neck to constrain subsequent embolization coils of a wide-necked cerebral aneurysm. None of the patients experienced any periprocedural or delayed neurological complications. This maneuver enabled us to support the coil loops within the aneurismal sac with stabilization of the microcatheter. CONCLUSION: The stent-jail technique represents an efficacious adjuvant technique to assist coiling of selected wide-necked cerebral aneurysms. This technique is particularly helpful for wide-necked aneurysms.