Background
Disturbance of cholesterol homeostasis is considered as one of the manifestations of cancer. Cholesterol plays an essential role in the pleiotropic functions of cancer cells, including ...mediating membrane trafficking, intracellular signal transduction, and production of hormones and steroids. As a single transmembrane receptor, the low-density lipoprotein receptor (LDLR) can participate in intracellular cholesterol uptake and regulate cholesterol homeostasis. It has recently been found that LDLR is aberrantly expressed in a broad range of cancers, including colon cancer, prostate cancer, lung cancer, breast cancer and liver cancer. LDLR has also been found to be involved in various signaling pathways, such as the MAPK, NF-κB and PI3K/Akt signaling pathways, which affect cancer cells and their surrounding microenvironment. Moreover, LDLR may serve as an independent prognostic factor for lung cancer, breast cancer and pancreatic cancer, and is closely related to the survival of cancer patients. However, the role of LDLR in some cancers, such as prostate cancer, remains controversial. This may be due to the lack of normal feedback regulation of LDLR expression in cancer cells and the severe imbalance between LDLR-mediated cholesterol uptake and de novo biosynthesis of cholesterol.
Conclusions
The imbalance of cholesterol homeostasis caused by abnormal LDLR expression provides new therapeutic opportunities for cancer. LDLR interferes with the occurrence and development of cancer by modulating cholesterol homeostasis and may become a novel target for the development of anti-cancer drugs. Herein, we systematically review the contribution of LDLR to cancer progression, especially its dysregulation and underlying mechanism in various malignancies. Besides, potential targeting and immunotherapeutic options are proposed.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
SFTSV, a tick-borne bunyavirus causing a severe hemorrhagic fever termed as severe fever with thrombocytopenia syndrome (SFTS). To evaluate the potential role of rodents and its ectoparasitic ...chiggers in the transmission of SFTSV, we collected wild rodents and chiggers on their bodies from a rural area in Qingdao City, Shandong Province, China in September 2020. PCR amplification of the M and L segments of SFTSV showed that 32.3% (10/31) of rodents and 0.2% (1/564) of chiggers (
Leptotrombidium deliense
) from the rodents were positive to SFTSV. Our results suggested that rodents and chiggers may play an important role in the transmission of SFTSV, although the efficiency of chiggers to transmit SFTSV needs to be further investigated experimentally.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract
Quantifying inter-specific variations of tree resilience to drought and revealing the underlying mechanisms are of great importance to the understanding of forest functionality, particularly ...in water-limited regions. So far, comprehensive studies incorporating investigations in inter-specific variations of long-term growth patterns of trees and the underlying physiological mechanisms are very limited. Here, in a semi-arid site of northern China, tree radial growth rate, inter-annual tree-ring growth responses to climate variability, as well as physiological characteristics pertinent to xylem hydraulics, carbon assimilation and drought tolerance were analyzed in seven pine species growing in a common environment. Considerable inter-specific variations in radial growth rate, growth response to drought and physiological characteristics were observed among the studied species. Differently, the studied species exhibited similar degrees of resistance to drought-induced branch xylem embolism, with water potential corresponding to 50% loss hydraulic conductivity ranging from −2.31 to −2.96 MPa. We found that higher branch hydraulic efficiency is related to greater leaf photosynthetic capacity, smaller hydraulic safety margin and lower woody density (P < 0.05, linear regressions), but not related to higher tree radial growth rate (P > 0.05). Rather, species with higher hydraulic conductivity and photosynthetic capacity were more sensitive to drought stress and tended to show weaker growth resistance to extreme drought events as quantified by tree-ring analyses, which is at least partially due to a trade-off between hydraulic efficiency and safety across species. This study thus demonstrates the importance of drought resilience rather than instantaneous water and carbon flux capacity in determining tree growth in water-limited environments.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
AIM To explore the role of macrophages in chronic pancreatitis(CP) and the effect of Dachaihu decoction(DCHD) on pancreatic fibrosis in mice.METHODS Kun Ming mice were randomly divided into a control ...group, CP group, and DCHD group. In the CP and DCHD groups, mice were intraperitoneally injected with 20% L-arginine(3 g/kg twice 1 d/wk for 6 wk). Mice in the DCHD group were administered DCHD intragastrically at a dose of 14 g/kg/d 1 wk after CP induction. At 2 wk, 4 wk and 6 wk post-modeling, the morphology of the pancreas was observed using hematoxylin and eosin, and Masson staining. Interleukin-6(IL-6) serum levels were assayed using an enzyme-linked immunosorbent assay. Double immunofluorescence staining was performed to observe the co-expression of F4/80 and IL-6 in the pancreas. Inflammatory factors including monocyte chemoattractant protein-1(MCP-1), macrophage inflammatory protein-1α(MIP-1α) and IL-6 were determined using real time-polymerase chain reaction. Western blot analysis was used to detect fibronectin levels in the pancreas. RESULTS Compared with the control group, mice with 20% L-arginine-induced CP had obvious macrophage infiltration and a higher level of fibrosis. IL-6 serum concentrations were significantly increased. Double immunofluorescence staining showed that IL-6 and F4/80 were co-expressed in the pancreas. With the administration of DCHD, the infiltration of macrophages and degree of fibrosis in the pancreas were significantly attenuated; IL-6, MCP-1 and MIP-1α m RNA, and fibronectin levels were reduced. CONCLUSION The dominant role of macrophages in the development of CP was mainly related to IL-6 production. DCHD was effective in ameliorating pancreatic fibrosis by inhibiting macrophage infiltration and inflammatory factor secretion in the pancreas.
MiRNA accounts for 1–3% of genes but regulates more than 30% of gene expression in humans. This article analyzes the current deficiencies and challenges of miR-411 research and looks forward to the ...prospects of miR-411 in cancer. MiR-411 is a non-coding RNA located on chromosome 14. MiR-411 is abnormally expressed in a variety of cancers. The dysregulation of miR-411 can affect cancer cell proliferation, invasion, migration, apoptosis, colony formation, etc. miR-411 can be regulated by different lncRNAs and circRNAs. By targeting multiple genes, miR-411 participates in the activation of the MAPK signaling pathway, PI3K/AKT/mTOR signaling pathway, p53 signaling pathway, Ras signaling pathway, NF-κB signaling pathway, and Wnt/β-catenin signaling pathway. The expression of miR-411 is related to the diagnosis, prognosis, and sensitivity of drugs in cancer patients. In conclusion, this work outlines the molecular mechanisms and cellular functions of aberrant expression of miR-411 and its target genes in cancer to reveal its potential value in diagnosis, prognosis, and drug sensitivity.
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•Aberrant expression of miR-411 is related to cancer diagnosis and prognosis.•MiR-411 participates in the activation of five signaling pathways in cancer.•Dysregulation of miR-411 affects the behaviors of cancer cells.•MiR-411 is related to the sensitivity of drugs in cancer patients.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Low-molecular mass protein 7 (LMP7) is a proteolytic subunit of the immunoproteasome that is involved in regulating inflammatory responses. However, the role of LMP7 in the pathogenesis of abdominal ...aortic aneurysm (AAA) remains unknown. In this study, ApoE knockout (KO) or LMP7/ApoE double KO (dKO) mice were infused with angiotensin II (Ang II, 1000 ng/kg per minute) for up to 28 d. We found that LMP7 expression was significantly upregulated in AAA tissues from ApoE KO mice and human patients. Moreover, Ang II infusion markedly increased the incidence and severity of AAA in ApoE KO mice, which was considerably reduced in LMP7/ApoE dKO mice. Histological alterations, including aortic wall thickening, collagen deposition, elastin fragmentation, and vascular smooth muscle cell apoptosis in AAA tissue of ApoE KO mice, were also significantly attenuated in LMP7/ApoE dKO mice. Interestingly, LMP7/ApoE dKO mice showed a marked reduction of infiltration of CD3
T cells, especially CD4
T cells in AAA tissues compared with ApoE KO mice. Moreover, ablation of LMP7 substantially inhibited the differentiation of CD4
T cells into Th1 and Th17 cells by reducing the activation of multiple transcriptional factors. We also investigated the effects of an LMP7-specific inhibitor PR-957 (also known as ONX 0914) on AAA formation in ApoE KO mice. PR-957 treatment could reduce the AAA incidence and severity. In conclusion, our results provide, to our knowledge, novel evidence that ablation or pharmacological inhibition of LMP7 attenuates Ang II-induced AAA formation, and LMP7 might be a novel therapeutic target for treating AAA in humans.
•Enriched environment contributes to an increased conversion of proBDNF to BDNF within the hippocampus.•Enriched environment elevates MMP-9 within the hippocampus.•The post-translation process of ...BDNF might facilitate the synaptic plasticity.•Enriched environment reduces anxiety-like behavior and has a potential anti-depressive effect.
An enriched environment has been shown to influence brain plasticity and function by involving the action of brain-derived neurotrophic factor (BDNF). BDNF, which is synthesized as a precursor molecule (proBDNF) that undergoes proteolytic cleavage, plays an important role in synaptic plasticity and contributes to several brain functions such as memory, learning, and behavior. The neurotrophins and proneurotrophins often play opposite roles in the brain, suggesting that proteolytic cleavage of proneurotrophins controls the action of neurotrophins. However, few studies have focused on the expression and cleavage of proBDNF after exposure to an enriched environment. Our study aimed to explore the effects of an early-enriched environment on the conversion of proBDNF to BDNF in the adult rats’ hippocampus. We found that there was no difference in the expression of proBDNF in the hippocampus between the SE (standard environment) and EE (enriched environment) rats, but a significantly increased BDNF protein level was found in the EE rats. Thus, a remarkably enhanced ratio of BDNF to proBDNF (BDNF/proBDNF) was observed in the EE rats. In addition, the EE resulted in a remarkably up-regulated matrix metalloproteinase-9 (MMP-9) in the hippocampus, which played a key role in converting proBDNF to BDNF in the extracellular space. Furthermore, the expression of synapse-related proteins (NR1 and NR2A) was analyzed, and the results indicated that EE could significantly increase the expression of NR1 and NR2A in the hippocampus. In addition, the behavioral results showed that EE reduced anxiety-like behavior in the elevated-plus maze test and reduced immobility time in the forced swimming test. Moreover, the EE resulted in an increased preference for sucrose compared to the SE. These results suggested that the EE up-regulated MMP-9 levels within the hippocampus, which might facilitate the conversion of proBDNF to BDNF, thereby contributing to the long lasting alterations of synaptic plasticity and behavior.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
•BFT can efficiently decompose nitrogen, phosphorus and other pollutants in aquaculture water.•BFT can enhance the growth performance and digestive enzyme activity of golden crucian carp.•BFT can ...enhance the autoimmunity and antioxidant capacity of cultured animals.•The most suitable C/N ratio for the growth of golden crucian carp is 20:1.
A 56-day feeding trial was implemented to evaluate the effects of promoted biofloc on the water quality, growth performance, digestive enzymes activity, immune-related genes and antioxidant status of golden crucian carp in negligible exchange culture tanks. Four handred fifty healthy golden crucian carp juveniles (5.03 ± 0.22 g) were randomly assigned among 15 tanks. Five C:N ratios in triplicate tanks were tried: C/N = 5.48:1 with a commercial diet (Control), C/N = 10:1, C/N = 15:1, C/N = 20:1 and C/N = 25:1. Anhydrous glucose (99.97 %) was added to the commercial diet to maintain elevated carbon ratio in the three treatments. Uninterrupted 24 -h aeration was supplied during the test by using an air-stone connected to an air pump to develop the biofloc in the water column. The results demonstrated that BFT significantly reduced ammonia nitrogen (TAN), nitrite (NO2−-N), total phosphorus (TP) concentration and water transparency (Secchi depth) in C/N 15–25 than control (p < 0.05), wheras the chemical oxygen demand (COD) and nitrate nitrogen (NO3−-N) concentration gradually increased over time. Apart from, weight gain (WG), specific growth rate (SGR), and protein efficiency ratio (PER) were considerately elevated in C/N 20 and C/N 25 than control (p < 0.05).This was coincidental with the higher activities for protease, lipase and amylase in liver. Significant increases in lysozyme (LSZ), acid phosphatase (ACP) and alkaline phosphatase (AKP) activities of golden crucian carp were found in the C/N 20 group than control (p < 0.05), and regulating the expression of immune-related genes including IL-1β, TNF-α and HSP70 after a 56-day feeding trial. Comparing the antioxidant capacity of golden crucian carp from the five experimental groups, the activity of superoxide dismutase (SOD), total antioxidant capacity (T-AOC), catalase (CAT) activity and glutathione peroxidase (GSH-PX) activity of juveniles in the C/N 20 and C/N 25 groups were significant higher (p < 0.05), and the content of malondialdehyde (MDA) was much lower (p < 0.05) than in the control under this experiment condition. Overall, this findings suggest that BFT not only can enhance golden crucian carp growth performance, elevate digestive enzymes activity, and strengthen antioxidant status but also upgrade immune response.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Few studies have reported the timing and amount of gestational weight gain (GWG) to prevent large‐for‐gestational‐age (LGA) or small‐for‐gestational‐age (SGA). This study aimed to evaluate the ...association of GWG velocity in each trimester with LGA or SGA based on data from the Taicang and Wuqiang cohort study (TAWS, n = 2008). We used a linear mixed model to evaluate the association of trimester‐specific GWG velocity with birthweight categories and stratified by prepregnancy body mass index category and parity. For normal‐weight pregnant women, mothers with LGA births had higher GWG velocities than mothers with appropriate‐for‐gestational‐age (AGA) births in the first trimester (0.108 vs. 0.031 kg/week, p < 0.01), second trimester (0.755 vs. 0.631 kg/week, p < 0.01) and third trimester (0.664 vs. 0.594 kg/week, p < 0.01); in contrast, mothers with SGA births had lower GWG velocities than mothers with AGA births in the second trimester (0.528 vs. 0.631 kg/week, p < 0.01) and third trimester (0.541 vs. 0.594 kg/week, p < 0.01). For normal‐weight pregnant women with AGA births, multiparous women had lower GWG velocities than primiparous women in the second (0.602 vs. 0.643 kg/week, p < 0.01) and third trimesters (0.553 vs. 0.606 kg/week, p < 0.01). Therefore, for normal‐weight women, LGA prevention would begin in early pregnancy and continue until delivery and the second and third trimesters may be critical periods for preventing SGA; in addition, among normal‐weight pregnant women with AGA births, multiparous women tend to have lower weight gain velocities than primiparous women.
Gestational weight gain velocities were associated with birthweight‐for‐gestational‐age categories. Large‐for‐gestational‐age prevention would begin in early pregnancy and continue until delivery, while the second and third trimesters may be the critical periods for small‐for‐gestational‐age prevention. Among normal‐weight pregnant women with appropriate‐for‐gestational‐age births, multiparous women tend to have lower weight gain velocities than primiparous women.
Key messages
Mothers with large‐for‐gestational‐age births had higher weight gain velocities throughout pregnancy.
Mothers with small‐for‐gestational‐age births had lower weight gain velocities in the second and third trimesters.
Large‐for‐gestational‐age prevention would begin in early pregnancy and continue until delivery, while the second and third trimesters may be critical periods for small‐for‐gestational‐age prevention.
Among normal‐weight pregnant women with appropriate‐for‐gestational‐age newborns, multiparous women tend to have lower weight gain velocities than primiparous women.
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FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK
Perennial ryegrass (
) is widely cultivated around the world for turf and forage. However, the plant is highly susceptible to disease and is sensitive to drought. The present study aims to determine ...the effect of the fungal endophyte
var.
of perennial ryegrass on the combined stresses of drought and disease caused by
in the greenhouse. In the experiment, plants infected (E+) or not infected (E-) with the fungal endophyte were inoculated with
and put under different soil water regimes (30%, 50%, and 70%). The control treatment consisted of E+ and E- plants not inoculated with
. Plant growth, phosphorus (P) uptake, photosynthetic parameters, and other physiological indices were evaluated two weeks after pathogen infection. The fungal endophyte in E+ plants increased P uptake, plant growth, and photosynthetic parameters but decreased the malondialdehyde concentration, proline content, and disease incidence of perennial ryegrass (
< 0.05). E+ plants had the lowest disease incidence at 70% soil water (
< 0.05). The study demonstrates that the fungal endophyte
var.
is beneficial for plant growth and stress tolerance in perennial ryegrass exposed to the combined stresses of drought and
.