Osthole Ameliorates Renal Fibrosis in Mice by Suppressing Fibroblast Activation and Epithelial-Mesenchymal Transition

Renal fibrosis is a common pathway of virtually all progressive kidney diseases. Osthole (OST, 7-Methoxy-8-(3-methylbut-2-enyl)-2-chromenone), a derivative of coumarin mainly found in plants of the Apiaceae family, has shown inhibitory effects on inflammation, oxidative stress, fibrosis and tumor progression. The present study investigated whether OST mediates its effect via suppressing fibroblast activation and epithelial-mesenchymal transition (EMT) in unilateral ureteral obstruction (UUO)-induced renal fibrosis in mice. Herein, we found that OST inhibited fibroblast activation in a dose-dependent manner by inhibiting the transforming growth factor-β1 (TGFβ1)-Smad pathway. OST also blocked fibroblast proliferation by reducing DNA synthesis and downregulating the expressions of proliferation- and cell cycle-related proteins including proliferating cell nuclear antigen (PCNA), CyclinD1 and p21 Waf1/Cip1. Meanwhile, in the murine model of renal interstitial fibrosis induced by UUO, myofibroblast activation with increased expression of α-smooth muscle actin (α-SMA) and proliferation were attenuated by OST treatment. Additionally, we provided in vivo evidence suggesting that OST repressed EMT with preserved E-cadherin and reduced Vimentin expression in obstructed kidney. UUO injury-induced upregulation of EMT-related transcription factors, Snail family transcriptional repressor-1(Snail 1) and Twist family basic helix-loop-helix (BHLH) transcription factor (Twist) as well as elevated G2/M arrest of tubular epithelial cell, were rescued by OST treatment. Further, OST treatment reversed aberrant expression of TGFβ1-Smad signaling pathway, increased level of proinflammatory cytokines and NF-kappaB (NF-κB) activation in kidneys with obstructive nephropathy. Taken together, these findings suggest that OST hinder renal fibrosis in UUO mouse mainly through inhibition of fibroblast activation and EMT

High Diversity of Tick-associated Microbiota from Five Tick Species in Yunnan, China

Ticks are obligate blood-sucking vectors for multiple zoonotic diseases. In this study, tick samples were collected from Yunnan Province, China, which is well-known as the “Global Biodiversity Hotspot” in the world. This study aimed to clarify the microbial populations, including pathogens, associated with ticks and to identify the diversity of tick-borne microbiota in this region. The 16S rRNA full-length sequencing from pooled tick DNA samples and PCR amplification of pathogenic genera from individual samples were performed to understand tick-associated microbiota in this region. A total of 191 adult ticks of 5 tick species were included and revealed 11 phyla and 126 genera bacteria, including pathogenic Anaplasma , Ehrlichia , Candidatus Neoehrlichia, Rickettsia , Borrelia , and Babesia . Further identification suggested that Rickettsia sp. YN01 was a variant strain of Rickettsia spp. IG-1, but Rickettsia sp. YN02 and Rickettsia sp. YN03, were potentially two new SFGR species. This study revealed the complexity of ecological interactions between host and microbe and provided insight for the biological control of ticks. A high microbial diversity in ticks from Yunnan was identified, and more investigation should be undertaken to elucidate the pathogenicity in the area

MAP4 Mechanism that Stabilizes Mitochondrial Permeability Transition in Hypoxia: Microtubule Enhancement and DYNLT1 Interaction with VDAC1

Mitochondrial membrane permeability has received considerable attention recently because of its key role in apoptosis and necrosis induced by physiological events such as hypoxia. The manner in which mitochondria interact with other molecules to regulate mitochondrial permeability and cell destiny remains elusive. Previously we verified that hypoxia-induced phosphorylation of microtubule-associated protein 4 (MAP4) could lead to microtubules (MTs) disruption. In this study, we established the hypoxic (1% O2) cell models of rat cardiomyocytes, H9c2 and HeLa cells to further test MAP4 function. We demonstrated that increase in the pool of MAP4 could promote the stabilization of MT networks by increasing the synthesis and polymerization of tubulin in hypoxia. Results showed MAP4 overexpression could enhance cell viability and ATP content under hypoxic conditions. Subsequently we employed a yeast two-hybrid system to tag a protein interacting with mitochondria, dynein light chain Tctex-type 1 (DYNLT1), by hVDAC1 bait. We confirmed that DYNLT1 had protein-protein interactions with voltage-dependent anion channel 1 (VDAC1) using co-immunoprecipitation; and immunofluorescence technique showed that DYNLT1 was closely associated with MTs and VDAC1. Furthermore, DYNLT1 interactions with MAP4 were explored using a knockdown technique. We thus propose two possible mechanisms triggered by MAP4: (1) stabilization of MT networks, (2) DYNLT1 modulation, which is connected with VDAC1, and inhibition of hypoxia-induced mitochondrial permeabilization

Identification of Disease-Transmitting Mosquitoes: Development of Species-Specific Probes for DNA Chip Assay Using Mitochondrial COI and ND2 Genes and Ribosomal Internal Transcribed Spacer 2

Mosquitoes, which transmit infectious diseases, such as malaria and dengue fever, are harmful to human health. Thus, accurate and rapid identification of vectors is a critical step for the control of mosquito-borne diseases. However, phenotypic variations in adults, lack of recognizable features of the immature, and fragility of mosquitoes make identification difficult. Molecular approaches have been widely applied to identify mosquitoes, yet these methods have been focused only on the identification of a few species. This study used sequences of two mitochondrial genes, COI and ND2, and a ribosomal gene, ITS2, to design species-specific probes. Biochips thus developed were able to provide simultaneous identification of nine important medical and veterinary species, including the immature, from genera of Aedes, Anopheles, Armigeres, and Culex. This chip was also applied to samples collected from the field. Despite its inability to resolve the close affinity species of Culex quinquefasciatus and Culex pipiens molestus, pertinent biochips are expected to be applied to a mass screening method

Homogeneity of delta N-15 in needles of Masson pine (Pinus massoniana L.) was altered by air pollution

The present study investigated the changes of δ N values in the tip, middle and base section (divided by the proportion to needle length) of current- and previous-year needles of Masson pine (Pinus massoniana L.) from two declining forest stands suffering from air pollution, in comparison with one healthy stand. At the healthy stand, δ N in the three sections of both current- and previous-year needles were found evenly distributed, while at the polluted stands, δ N values in the needles were revealed significantly different from the tip to the base sections. The results implied that the distribution of δ N among different parts or sections in foliages was not always homogeneous and could be affected by air pollution. We suggested that the difference of δ N values among pine needle sections should be reconsidered and should not be primarily ignored when the needle δ N values were used to assess plant responses to air pollution

Statins decrease overall mortality and cancer related mortality but are underutilized in NAFLD: a longitudinal analysis of 12,538 individuals

Expert Review of Gastroenterology & Hepatology169895-90