The abundant and reversible N6‐methyladenosine (m6A) R
NA
modification and its modulators have important roles in regulating various gene expression and biological processes. Here, we demonstrate that fat mass and obesity associated (
FTO
), as an m6A demethylase, plays a critical anti‐tumorigenic role in clear cell renal cell carcinoma (cc
RCC
).
FTO
is suppressed in cc
RCC
tissue. The low expression of
FTO
in human cc
RCC
correlates with increased tumour severity and poor patient survival. The Von Hippel‐Lindau‐deficient cells expressing
FTO
restores mitochondrial activity, induces oxidative stress and
ROS
production and shows impaired tumour growth, through increasing expression of
PGC
‐1α by reducing m6A levels in its
mRNA
transcripts. Our work demonstrates the functional importance of the m6A methylation and its modulator, and uncovers a critical
FTO
‐
PGC
‐1α axis for developing effective therapeutic strategies in the treatment of cc
RCC
.
Illustration showing the fabrication process and test contents of electrospun gelatin nanofibers loaded with vitamins A and E as wound dressing materials in this paper.
To obtain wound dressings which could be removed easily without secondary injuries, we prepared thermoresponsive electrospun fiber mats containing poly(di(ethylene glycol) methyl ether methacrylate) (PDEGMA). Blend fibers of PDEGMA and poly(l-lactic acid-co-ε-caprolactone) (P(LLA-CL) were fabricated via electrospinning, and analogous fibers containing the antibiotic ciprofloxacin (CIF) were also prepared. Smooth cylindrical fibers were obtained, albeit with a small amount of beading visible for the ciprofloxacin-loaded fibers. X-ray diffraction showed the drug to exist in the amorphous physical form post-electrospinning. The composite fibers showed distinct thermosensitive properties and gave sustained release of CIF over more than 160h in vitro. The fibers could promote the proliferation of fibroblasts, and by varying the temperature cells could easily be attached to and detached from the fibers. Antibacterial tests demonstrated that fibers loaded with ciprofloxacin were effective in inhibiting the growth of E. coli and S. aureus. In vivo investigations on rats indicated that the composite PDEGMA/P(LLA-CL) fibers loaded with CIF had much more potent wound healing properties than a commercial gauze and CIF-loaded fibers made solely of P(LLA-CL). These results demonstrate the potential of PDEGMA/P(LLA-CL)/ciprofloxacin fibers as advanced wound dressing materials.
LAG3 is the most promising immune checkpoint next to PD-1 and CTLA-4. High LAG3 and FGL1 expression boosts tumor growth by inhibiting the immune microenvironment. This review comprises four sections presenting the structure/expression, interaction, biological effects, and clinical application of LAG3/FGL1. D1 and D2 of LAG3 and FD of FGL1 are the LAG3-FGL1 interaction domains. LAG3 accumulates on the surface of lymphocytes in various tumors, but is also found in the cytoplasm in non-small cell lung cancer (NSCLC) cells. FGL1 is found in the cytoplasm in NSCLC cells and on the surface of breast cancer cells. The LAG3-FGL1 interaction mechanism remains unclear, and the intracellular signals require elucidation. LAG3/FGL1 activity is associated with immune cell infiltration, proliferation, and secretion. Cytokine production is enhanced when LAG3/FGL1 are co-expressed with PD-1. IMP321 and relatlimab are promising monoclonal antibodies targeting LAG3 in melanoma. The clinical use of anti-FGL1 antibodies has not been reported. Finally, high FGL1 and LAG3 expression induces EGFR-TKI and gefitinib resistance, and anti-PD-1 therapy resistance, respectively. We present a comprehensive overview of the role of LAG3/FGL1 in cancer, suggesting novel anti-tumor therapy strategies.
Long Noncoding RNAs (lncRNAs) are a kind of non-protein coding transcripts longer than 200 nucleotides, and play important roles in diverse biological processes, such as embryonic development and apoptosis. Homeobox (HOX) transcript antisense intergenic RNA (HOTAIR) is a negative prognostic factor in a variety of human cancers, such as breast, liver and lung cancers. HOTAIR can promote cancer cell metastasis by reprogramming chromatin organization. In the present study, HOTAIR expression was elevated in tissues of renal cell carcinoma compared to adjacent normal tissues, and positively correlated with metastasis (P<0.05). The cell migration was inhibited in scratch test and transwell assay after HOTAIR knockdown (P<0.05). Further researches revealed that histone demethylase JMJD3 was reduced and its target gene Snai1 expression was down-regulated after HOTAIR suppression (P<0.05). Meanwhile, the level of histone methytransferase EZH2 target gene PCDHB5 was increased (P<0.05). Collectively, these data suggest that HOTAIR is an important promoter in metastasis of renal cell carcinoma and also plays a dual regulatory role in chromatin state by effecting both histone metylation and demethylation at different gene loci.
Above‐ground and below‐ground interactions of the maize–soybean intercrop were studied in a 2‐yr field experiment with measurements of grain and total biological yield; N, P, and K uptake; and photosynthesis. Four intercrop treatments included no shoot or root separation (T1), shoot and root separation (T2), root separation (T3), and shoot separation (T4); two controls were solo maize (T5) and solo soybean (T6). Results indicated that competition between above‐ground and/or below‐ground plant parts is a key factor in describing intercropping advantage, and that intercropping is not advantageous in the absence of competition. Specific results showed significant intercrop advantages when roots and shoots were not separated, the differences between component species in above‐ground and below‐ground competition, and a greater contribution to intercrop advantages from below‐ground interactions than above‐ground interactions. Although competition for nutrients, water, and sunlight is the primary explanation often used to explain intercrop advantages, our results indicate that competition for nutrients was of more importance than competition for sunlight. Differences in nutrient uptake data were closely related to those of yields, confirming the importance of below‐ground competition. Relatively less competition above ground was confirmed by minimal differences in photosynthesis among treatments. More refined studies of resource competition could further confirm the different contributions of above‐ground and below‐ground interactions. One potential application of results could be their use in intercrop systems modeling.
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