Effects of sodium glucose cotransporter-2 inhibitors on serum uric acid in type 2 diabetes mellitus: A systematic review with an indirect comparison meta-analysis

To describe the effects of sodium-glucose co-transporter 2 (SGLT2) inhibitors on serum uric acid (SUA) in patients with type 2 diabetes mellitus (T2DM). PubMed, EMBASE, and CENTRAL were searched for randomized controlled trials of SGLT2 inhibitors in patients with T2DM up to Aug 10, 2017, without language or date restrictions. Thirty-one studies totaling 13,650 patients were included. SGLT2 inhibitors significantly decreased SUA levels compared with placebo, canagliflozin WMD –37.02?μmol/L, 95% CI [–38.41, –35.63], dapagliflozin WMD –38.05?μmol/L, 95% CI [–44.47, –31.62], empagliflozin WMD –42.07?μmol/L, 95% CI [–46.27, –37.86]. The drug class effect of SUA reduction suggesting SGLT2 inhibitors might be beneficial for diabetic patients with hyperuricemia.     

Porphyromonas gingivalis promotes the motility of esophageal squamous cell carcinoma by activating NF-κB signaling pathway

Esophageal carcinoma, with a increasing incidence, is one of the most aggressive carcinomas in gastrointestinal tract. Epidemiologic studies demonstrate an association of oral pathogens with multiple diseases, including rheumatoid arthritis, cardiovascular diseases, diabetes, and gastrointestinal malignancies. Nevertheless, a causal relationship between oral pathogens and esophageal squamous cell carcinoma (ESCC) has not been elucidated. Here, we found that Porphyromonas was significantly enriched in the saliva of patients with ESCC, compared with that in normal human. In vitro studies showed that Porphyromonas gingivalis (P. gingivalis) promoted the proliferation and motility of ESCC cells, as evidenced by up regulated expression of key molecules implicated in NF-κB signaling pathway. These findings, for the first time, demonstrated a role of oral pathogens in inducing ESCC tumorigenesis and metastasis, which might involve regulation of NF-κB signaling pathway.     

Traits of fatty acid accumulation in dimorphic seeds of the euhalophyte Suaeda salsa in saline conditions

The mechanism on of how salinity affects seed fatty acids accumulation remains unclear in halophytes. The present results revealed that the content of total unsaturated fatty acids in black seeds was higher than in brown seeds in the euhalophyte Suaeda salsa under controlled saline conditions. Salinity (200?mM NaCl) significantly increased the total oil content, unsaturated acid/saturated acid ratio, and content of α-linolenic acid (C18:3) (ALA), especially in brown seeds. The most abundant fatty acid in dimorphic seeds is linoleic acid (C18:2) (>70%). It appears that more ALA accumulated in brown seeds compared to black seeds. The enzyme activity of omega-3 fatty acid desaturase (ω-3 FAD) in brown seeds was much higher than that in black seeds, but salinity had no significant effect on the activity of ω-3 FAD in both brown and black seeds. The relative expression of SsFAD7 was increased by salinity, and the value in brown seeds was much higher than that in black seeds. This means salinity can, salinity can improve the quantity of fatty acids in dimorphic seeds of S. salsa, and the enzyme of ω-3 FAD and SsFAD7 may involve in the accumulation of ALA in dimorphic seeds under salinity.     

Long‐term changes in the impacts of global warming on leaf phenology of four temperate tree species

Contrary to the generally advanced spring leaf unfolding under global warming, the effects of the climate warming on autumn leaf senescence are highly variable with advanced, delayed, and unchanged patterns being all reported. Using one million records of leaf phenology from four dominant temperate species in Europe, we investigated the temperature sensitivities of spring leaf unfolding and autumn leaf senescence (S_T, advanced or delayed days per degree Celsius). The S_T of spring phenology in all of the four examined species showed an increase and decrease during 1951–1980 and 1981–2013, respectively. The decrease in the S_T during 1981–2013 appears to be caused by reduced accumulation of chilling units. As with spring phenology, the S_T of leaf senescence of early successional and exotic species started to decline since 1980. In contrast, for late successional species, the S_T of autumn senescence showed an increase for the entire study period from 1951 to 2013. Moreover, the impacts of rising temperature associated with global warming on spring leaf unfolding were stronger than those on autumn leaf senescence. The timing of leaf senescence was positively correlated with the timing of leaf unfolding during 1951–1980. However, as climate warming continued, the differences in the responses between spring and autumn phenology gradually increased, so that the correlation was no more significant during 1981–2013. Our results further suggest that since 2000, due to the decreased temperature sensitivity of leaf unfolding the length of the growing season has not increased any more. These finding needs to be addressed in vegetation models used for assessing the effects of climate change.     

Satellite detection of cumulative and lagged effects of drought on autumn leaf senescence over the Northern Hemisphere

Climate change has substantial influences on autumn leaf senescence, that is, the end of the growing season (EOS). Relative to the impacts of temperature and precipitation on EOS, the influence of drought is not well understood, especially considering that there are apparent cumulative and lagged effects of drought on plant growth. Here, we investigated the cumulative and lagged effects of drought (in terms of the Standardized Precipitation–Evapotranspiration Index, SPEI) on EOS derived from the normalized difference vegetation index (NDVI3g) data over the Northern Hemisphere extra‐tropical ecosystems (>30°N) during 1982–2015. The cumulative effect was determined by the number of antecedent months at which SPEI showed the maximum correlation with EOS (i.e., R_max‐cml) while the lag effect was determined by a month during which the maximum correlation between 1‐month SPEI and EOS occurred (i.e., R_max‐lag). We found cumulative effect of drought on EOS for 27.2% and lagged effect for 46.2% of the vegetated land area. For the dominant time scales where the R_max‐cml and R_max‐lag occurred, we observed 1–4 accumulated months for the cumulative effect and 2–6 lagged months for the lagged effect. At the biome level, drought had stronger impacts on EOS in grasslands, savannas, and shrubs than in forests, which may be related to the different root functional traits among vegetation types. Considering hydrological conditions, the mean values of both R_max‐cml and R_max‐lag decreased along the gradients of annual SPEI and its slope, suggesting stronger cumulative and lagged effects in drier regions as well as in areas with decreasing water availability. Furthermore, the average accumulated and lagged months tended to decline along the annual SPEI gradient but increase with increasing annual SPEI. Our results revealed that drought has strong cumulative and lagged effects on autumn phenology, and considering these effects could provide valuable information on the vegetation response to a changing climate.     

Structure-activity relationships study of neolamellarin A and its analogues as hypoxia inducible factor-1 (HIF-1) inhibitors

The novel marine pyrrole alkaloid neolamellarin A derived from sponge has been shown to inhibit hypoxia-induced HIF-1 activity. In this work, we designed and synthesized neolamellarin A and its series of derivatives by a convergent synthetic strategy. The HIF-1 inhibitory activity and cytotoxicity of these compounds were evaluated in Hela cells by dual-luciferase reporter gene assay and MTT assay, respectively. The results showed that neolamellarin A 1 (IC₅₀ = 10.8 ± 1.0 μM) and derivative 2b (IC₅₀ = 11.9 ± 3.6 μM) had the best HIF-1 inhibitory activity and low cytotoxicity. Our SAR research focused on the effects of key regions aliphatic carbon chain length, aromatic ring substituents and C-7 substituent on biological activity, providing a basis for the subsequent research on the development of novel pyrrole alkaloids as HIF-1 inhibitors and design of small molecule probes for target protein identification.     

Polymodal Nociception in Drosophila Requires Alternative Splicing of TrpA1

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