Peptidome analysis reveals the involvement of endogenous peptides in mouse pancreatic dysfunction with aging

Type 2 diabetes (T2D) is a glucose regulation disorder that has significantly enhanced mortality and the global disease burden. The prevalence of T2D has increased worldwide and is higher in the elderly. The function of pancreatic islets decreases with age, which is one important reason for the occurrence of diabetes in the elderly. Recently, peptidome analysis has attracted attention. However, the role of age-related peptides in pancreatic dysfunction has not been investigated extensively. Here, we conducted a comparison of endogenous peptides between pancreas from adult and aging mice by liquid chromatography tandem mass spectrometry (LC-MS/MS). A total of 2,089 peptides originating from 1,280 protein precursors were identified, of which 232 were upregulated and 183 were downregulated in the aging mice (fold change ≥ 2 and p < 0.05), suggesting that the expression of pancreatic peptides in mice varied with age. The molecular weight of most peptides was <3.0 kDa, and the isoelectric point distribution had a bimodal characteristic. Further analysis of cleavage site patterns indicated that proteases cleaved pancreatic proteins according to their rules. Moreover, Gene Ontology and pathway analyses showed that the differentially expressed peptides potentially had specific effects on pancreatic dysfunction. Some differential peptides were located within the domains of precursor proteins that were closely associated with the development of diabetes. We believe that our research may advance the current understanding of pancreas-derived peptides and that certain peptides may be involved in the etiology of diabetes.     

YAP regulates periodontal ligament cell differentiation into myofibroblast interacted with RhoA/ROCK pathway

During orthodontic tooth movement (OTM), periodontal ligament cells (PDLCs) receive the mechanical stimuli and transform it into myofibroblasts (Mfbs). Indeed, previous studies have demonstrated that mechanical stimuli can promote the expression of Mfb marker α-smooth muscle actin (α-SMA) in PDLCs. Transforming growth factor β1 (TGF-β1), as the target gene of yes-associated protein (YAP), has been proven to be involved in this process. Here, we sought to assess the role of YAP in Mfbs differentiation from PDLCs. The time-course expression of YAP and α-SMA was manifested in OTM model in vivo as well as under tensional stimuli in vitro. Inhibition of RhoA/Rho-associated kinase (ROCK) pathway using Y27632 significantly reduced tension-induced Mfb differentiation and YAP expression. Moreover, overexpression of YAP with lentiviral transfection in PDLCs rescued the repression effect of Mfb differentiation induced by Y27632. These data together suggest a crucial role of YAP in regulating tension-induced Mfb differentiation from PDLC interacted with RhoA/ROCK pathway.     

Inhibition of α-SMA by the Ectodomain of FGFR2c Attenuates Lung Fibrosis

The soluble ectodomain of fibroblast growth factor receptor-IIIc (sFGFR2c) is able to bind to fibroblast growth factor (FGF) ligands and block the activation of the FGF-signaling pathway. In this study, sFGFR2c inhibited lung fibrosis dramatically in vitro and in vivo. The upregulation of α-smooth muscle actin (α-SMA) in fibroblasts by transforming growth factor-β1 (TGF-β1) is an important step in the process of lung fibrosis, in which FGF-2, released by TGF-β1, is involved. sFGFR2c inhibited α-SMA induction by TGF-β1 via both the extracellular signal-regulated kinase 1/2 (ERK1/2) and Smad3 pathways in primary mouse lung fibroblasts and the proliferation of mouse lung fibroblasts. In a mouse model of bleomycin (BLM)-induced lung fibrosis, mice were treated with sFGFR2c from d 3 or d 10 to 31 after BLM administration. Then we used hematoxylin and eosin staining, Masson staining and immunohistochemical staining to evaluate the inhibitory effects of sFGFR2c on lung fibrosis. The treatment with sFGFR2c resulted in significant attenuation of the lung fibrosis score and collagen deposition. The expression levels of α-SMA, p-FGFRs, p-ERK1/2 and p-Smad3 in the lungs of sFGFR2c-treated mice were markedly lower. sFGFR2c may have potential for the treatment of lung fibrosis as an FGF-2 antagonist.     

The interspecific competition presents greater nutrient facilitation compared with intraspecific competition through AM fungi interacting with litter for two host plants in karst soil

AM 真菌和枯落物互作下两种喀斯特植物种间竞争较种内竞争更能促进植物养分利用 枯落物是植物养分获取和土壤养分转化的关键载体。丛枝菌根(Arbuscular mycorrhizae, AM)对植物养分摄取的影响已被广泛认知。然而，在养分亏缺的喀斯特生境中，不同竞争方式的植物如何通过AM真菌和枯落物利用养分尚不清楚。本研究对两种喀斯特适生植物构树(Broussonetia papyrifera)和云贵鹅耳枥(Carpinus pubescens)进行种内竞争和种  间竞争种植处理，并通过幼套球 囊霉(Glomus etunicatum)接种或不接种处理，以及土壤中添加或不添加两物种叶片混合枯落物处理，测定了植物生物量以及氮、磷、钾浓度等指标，研究植物的生长和养分利用。研究结果表明，AM真菌对两种植物养分摄取影响不同，AM真菌显著提高了种内和种间竞争下构树的养分摄取量，但降低了云贵鹅耳枥的养分摄取量。种间竞争下接种AM真菌，枯落物添加促进了云贵鹅耳枥对氮的摄取，抑制了构树对氮的摄取。接种AM真菌和添加枯落物条件下，种间竞争的构树对氮、磷和钾的摄取量及云贵鹅耳枥对氮的摄取量均高于种内竞争；种间竞争下两物种养分竞争力呈现明显差异，即构树对磷和钾养分竞争力显著提高，对氮则不显著；云贵鹅耳枥仅对钾的养分竞争力显著降低，对氮和磷则无显著影响。这些结果说明，在AM真菌与枯落物相互作用下，两种喀斯特植物种间竞争较种内竞争更能促进植物养分利用。     

α‐ketoglutarate delays age‐related fertility decline in mammals

The fecundity reduction with aging is referred as the reproductive aging which comes earlier than that of chronological aging. Since humans have postponed their childbearing age, to prolong the reproductive age becomes urgent agenda for reproductive biologists. In the current study, we examined the potential associations of α‐ketoglutarate (α‐KG) and reproductive aging in mammals including mice, swine, and humans. There is a clear tendency of reduced α‐KG level with aging in the follicle fluids of human. To explore the mechanisms, mice were selected as the convenient animal model. It is observed that a long term of α‐KG administration preserves the ovarian function, the quality and quantity of oocytes as well as the telomere maintaining system in mice. α‐KG suppresses ATP synthase and alterations of the energy metabolism trigger the nutritional sensors to down‐regulate mTOR pathway. These events not only benefit the general aging process but also maintain ovarian function and delay the reproductive decline. Considering the safety of the α‐KG as a naturally occurring molecule in energy metabolism, its utility in reproduction of large mammals including humans deserves further investigation.