Advanced glycation end products (AGE) are involved in the alterations of renal mesangial cell (MCs) growth, a feature of early stages of diabetic nephropathy (DN). We postulate that morroniside and loganin, 2 components extracted from Cornus officinalis, may ameliorate the detrimental effects of AGE-induced MCs proliferation by preventing oxidative stress. Rat MCs cultured in AGE milieu were treated with morroniside and loganin. Results showed that morroniside and loganin inhibited AGE-induced MC proliferation as measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method. Fluorescence microscopy revealed that the morroniside and loganin improved the morphological changes of MCs. Flow cytometric analysis showed that morroniside and loganin inhibited the cell cycle of rat MCs. Furthermore, the level of reactive oxygen species was significantly reduced, and the activities of superoxide dismutase and glutathione peroxidase were markedly increased, whereas the level of malondialdehyde was not significantly reduced. These results suggest that morroniside and loganin regulate MC growth by preventing oxidative stress. Thus, this study provides a molecular basis for the use of morroniside and loganin in the early stages of DN.

BackgroundOvarian cancer is the most lethal gynecological malignant cancer in the female genital system. The dysfunction of miRNA contributes to ovarian cancer development.Material/MethodsThe miR-1271 level in ovarian cancer tissues and cells was assayed by qRT-PCR. The miR-1271 expression in cells was overexpressed by miRNA-mimic transfection and reduced by miRNA-antisense-oligonucleotide (ASO) transfection. Cell proliferation was analyzed by an MTT assay. The targeted genes were predicted by a bioinformatics algorithm and confirmed by a dual luciferase reporter assay. The protein level was assayed by Western blotting.ResultsThe ovarian cancer tissue and cell lines showed low levels of miR-1271. Low levels of miR-1271 in ovarian cancer tissues were correlated with a low rate of patient survival, and the overexpression of miR-1271 inhibited the proliferation of ovarian cancer cells. The 3′ UTR of cyclin G1 (CCNG1) was targeted by miR-1271.ConclusionsLow levels of miR-1271 in ovarian cancer tissues promoted cancer cell growth. MiR-1271 may be a new predictor of prognosis in ovarian cancer. MiR-1271 exerted its role by targeting CCNG1.

Diabetic nephropathy (DN), a common complication in patients with either type I or type II diabetes mellitus, has long been recognized to cause severe morbidity and mortality. It is also a major cause of chronic renal failure involved in dialysis therapy.1,2) DN is structurally characterized with the early appearance of hypertrophy in glomerular and tubular components, the subsequent development of thickened glomerular and tubular basement membranes, and the progressive accumulation of extracellular matrix (ECM) components in the glomerular mesangium and tubulointerstitium.3)The functional disorders were manifested by early microalbuminuria, renal hyperfiltration, hyperperfusion, and increasing capillary permeability to macromolecules, proteinuria and the end stage of renal failure (ESRF). 4)It has been postulated that DN occurs as a result of the interplay of metabolic and hemodynamic factors in the renal microcirculation. The main metabolic disorder of diabetes, chronic hyperglycemia, was accepted as a necessary prerequisite for the progression of DN. Hyperglycemia may act directly to damage the kidneys, 5) or may act indirectly through formation of advanced-glycation end products (AGEs), 6) activation of PKC pathway, 7) or causing abnormal expression of some important cytokines, among which TGF-b1 was reported to be the most important in the onset and progression of DN. TGF-b1 could stimulate mesangial cells uptaking glucose owing to overexpression of GLUT1, which leads to the acceleration of intracellular metabolic abnormalities in diabetes.8) TGF-b1 has been well proved to be a necessary prerequisite for the development of glomerular hypertrophy in streptozotocin-induced diabetic mice. 9) But the most important pathological effect of TGF-b1 may be that it can advance the expression of many kinds of ECM 10) and reduce their degradation by inhibiting enzyme activity of the matrix metalloproteinase (MMP) family.11) Both contribute to the accumulation of ECM in glomerular mesangium and tubulointestium, eventually causing glomerulosclerosis and tubulointerstitial fibrosis.Iridoid total glycoside from Cornus was a complex consisting mainly of morroniside and loganin. It had been previously proved capable of inhibiting overformation of AGEs in vitro and in vivo. Furthermore, its effect on partially recovering levels of some vasoactive factors and cytokines such as NO, ET, TNF-a and sICAM in the diabetes state had been reported. 12,13) Through morphological study, we had also observed that glomerulosclerosis in an experimental diabetes model was apparently prevented and retarded. To further elucidate its possible effects and mechanisms, the present study was designed to determine whether glomerular expression of TGF-b1, fibronectin, and laminin in diabetes rats induced by streptozotocin were restored to a certain degree by iridoid total glycoside treatment. MATERIALS AND METHODSIridoid Total Glycoside Iridoid total glycoside was kindly provided by Jiangsu Zhongkang new drug fingerprint R & D Co., Ltd. Its purity wa...

No abstract

Emerging SARS-CoV-2 variants of concern (VOCs) harboring multiple mutations in the spike protein raise concerns on effectiveness of current vaccines that rely on the ancestral spike protein. Here, we design a quadrivalent mosaic nanoparticle vaccine displaying spike proteins from the SARS-CoV-2 prototype and 3 different VOCs. The mosaic nanoparticle elicits equivalent or superior neutralizing antibodies against variant strains in mice and non-human primates with only small reduction in neutralization titers against the ancestral strain. Notably, it provides protection against infection with prototype and B.1.351 strains in mice. These results provide a proof of principle for the development of multivalent vaccines against pandemic and potential pre-emergent SARS-CoV-2 variants.