Eastern China experienced excessive Meiyu rainfall in the summer of 2020, with a long rainy season and frequent extreme rainfall events. Extreme rainfall occurred on daily to monthly time scales. In ...particular, persistent heavy rainfall events occurred; e.g., the maximum accumulated rainfall over four consecutive weeks (Rx28day) in the lower reaches of the Yangtze River was 94% greater than climatology, breaking the observational record since 1961. With ongoing anthropogenic climate change, it is vital to understand the anthropogenic influence on this extreme rainfall event and its driving mechanisms. In this study, based on multi-model simulations under different external forcings that participate in the Detection and Attribution Model Intercomparison Project (DAMIP) in the Coupled Model Intercomparison Project-phase 6 (CMIP6), we show that anthropogenic forcing has reduced the probability of the Rx28day extreme rainfall as that in observations in the lower reaches of the Yangtze River in 2020, by 46% (22–62%). Specifically, greenhouse gas (GHG) emissions have increased the probability by 44% as a result of atmospheric warming and moistening. However, this effect was offset by anthropogenic aerosols, which reduced the probability by 73% by reducing atmospheric moisture and weakening the East Asian summer monsoon circulation. With the continuous emissions of GHGs and reductions in aerosols in the future, similar persistent heavy rainfall events are projected to occur more frequently. A higher occurrence probability is expected under higher emission scenarios, which is estimated to be 4.6, 13.6 and 27.7 times that in the present day under the SSP1-2.6, SSP2-4.5, and SSP5-8.5 emission scenarios, respectively, by the end of the 21st century. Thus, efficient mitigation measures will help to reduce the impacts related to extreme rainfall.
In summer 2018, an extraordinary heat wave with record-breaking high temperatures hit Northeast Asia. However, the contribution of atmospheric circulation to this heat wave remains unknown. In this ...study, we quantify the contribution of circulation by using the flow analogue method. It is found that Northeast China, Korea and Japan were the most affected areas by the heat event, from daily to monthly timescales. The persistent high temperature was associated with an anticyclonic anomaly over Northeast Asia, related to the record-breaking northward shift of the western Pacific subtropical high (WPSH). The persistent anomalous anticyclone played a dominant role in this heat event, explaining half of the magnitude of the heat event. Both thermodynamical change and dynamical change in recent decades have increased the probability of occurrence of this kind of heat event over Northeast Asia. Specifically, the change in dynamical flow explains a fraction of less than 20% of the increases in probability of heat events. The contribution of thermodynamical changes to heat events generally increases with the rarity of the extreme event.
Exosomes are cell-derived nanovesicles with diameters from 30 to 150 nm, released upon fusion of multivesicular bodies with the cell surface. They can transport nucleic acids, proteins, and lipids ...for intercellular communication and activate signaling pathways in target cells. In cancers, exosomes may participate in growth and metastasis of tumors by regulating the immune response, blocking the epithelial–mesenchymal transition, and promoting angiogenesis. They are also involved in the development of resistance to chemotherapeutic drugs. Exosomes in liquid biopsies can be used as non-invasive biomarkers for early detection and diagnosis of cancers. Because of their amphipathic structure, exosomes are natural drug delivery vehicles for cancer therapy.
This review summarizes the biology, function, and applications of exosomes in cancers. Exosomes can be used as non-invasive biomarkers for early detection and diagnosis of cancers. Exosomes also act as natural drug delivery vehicles for cancer therapy. Display omitted
During summer 2021, Western North America (WNA) experienced an unprecedented heatwave with record-breaking high temperatures associated with a strong anomalous high-pressure system, i.e., a heat ...dome. Here, we use a flow analog method and find that the heat dome over the WNA can explain half of the magnitude of the anomalous temperature. The intensities of hot extremes associated with similar heat dome-like atmospheric circulations increase faster than background global warming in both historical change and future projection. Such relationship between hot extremes and mean temperature can be partly explained by soil moisture-atmosphere feedback. The probability of 2021-like heat extremes is projected to increase due to the background warming, the enhanced soil moisture-atmosphere feedback and the weak but still significantly increased probability of the heat dome-like circulation. The population exposure to such heat extremes will also increase. Limiting global warming to 1.5 °C instead of 2 °C (3 °C) would lead to an avoided impact of 53% (89%) of the increase in population exposure to 2021-like heat extremes under the RCP8.5-SSP5 scenario.
Objective
Withaferin A (WA) is a bioactive compound with a remarkable anti‐cancer effect derived from Withania somnifera, commonly known as ashwagandha. However, the anti‐cancer mechanisms of WA in ...glioblastoma multiforme (GBM) are still unclear.
Materials and Methods
Cell viability assays and xenografted nude mice were used to evaluate the effects of WA, along with flow cytometry to detect apoptosis and cell cycle of GBM. RNA‐seq analysis, Western blotting, immunofluorescence staining, qRT‐PCR and siRNA gene silencing were carried out to determine the signalling pathways affected by WA.
Results
Withaferin A significantly inhibited the growth of GBM in vitro and in vivo and triggered the intrinsic apoptosis of GBM cells by up‐regulating expression of Bim and Bad. WA arrested GBM cells at the G2/M phase of the cell cycle through dephosphorylating Thr161 of CDK1 by activating p53‐independent p21 up‐regulation. Knockdown of p21 restored cell cycle progression and cell viability by down‐regulating the expression of Bad rather than Bim. We demonstrated that endoplasmic reticulum (ER) stress induced by WA through the ATF4‐ATF3‐CHOP axis, initiated apoptosis and G2/M arrest in GBM cells.
Conclusion
We revealed a novel pathway that elucidated WA activation of apoptosis and G2/M arrest in GBM cells through the ATF4‐ATF3‐CHOP axis. This discovery is important for optimization of WA‐based regimens for prevention and/or treatment of GBM.
Apolipoproteins and cancer Ren, Liwen; Yi, Jie; Li, Wan ...
Cancer medicine (Malden, MA),
November 2019, Volume:
8, Issue:
16
Journal Article
Peer reviewed
Open access
The role of apolipoproteins in cardiovascular disease has been well investigated, but their participation in cancer has only been explored in a few published studies which showed a close link with ...certain kinds of cancer. In this review, we focused on the function of different kinds of apolipoproteins in cancers, autophagy, oxidative stress, and drug resistance. The potential application of apolipoproteins as biomarkers for cancer diagnosis and prognosis was highlighted, together with an investigation of their potential as drug targets for cancer treatment. Many important roles of apolipoproteins and their mechanisms in cancers were reviewed in detail and future perspectives of apolipoprotein research were discussed.
We focused on roles of different kind apolipoproteins in cancers, autophagy, oxidative stress, resistance of drugs and hypolipidemic agents and cancers. In addition, apolipoproteins as drug targets of cancer treatment and biomarkers for cancer diagnosis and prognosis were discussed. Future perspectives of apolipoproteins research were described in the end.
Breast cancer (BC) is the most common cancer in women and the second leading cause of their cancer death. Establishing an accurate BC prognosis is very difficult because of its heterogeneity. ...Elevated TFF1 levels in serum were associated with development of BC, TFF1 expression was upregulated in BC compared to the healthy breast tissue. The aim of this study was to investigate the function of TFF1 in BCs, and to assess whether serum TFF1 could be used in formulating a prognosis for BC patients. In silico analyses were carried out to determine the expression of TFF1 mRNA in different types of BC and the association between TFF1 expression and survival of BC patients. Expression of TFF1 protein was checked in 52 paraffin-embedded tissues of BCs by immunochemistry, and serum concentration of TFF1 in 70 BC patients and 32 healthy controls was measured by ELISA. Functional activities of TFF1 in BC cells were determined by CCK-8 assay, colony formation, BrdU-DNA synthesis, and assays for migration and invasion. Results showed that expression of TFF1 mRNA was correlated with expression of biomarkers of luminal cancers including ESR1, GATA3, FOXA1, MYB and XBP1. In addition, patients with ER+BC had higher expression of TFF1 than those with ER- (p < 0.05). There was also lower expression of TFF1 in triple-negative breast cancer (TNBC) than in non-TNBC (p < 0.05), which corresponds with the level of serum TFF1 in TNBC patients, compared with non-TNBC patients (p < 0.001). Furthermore, expression of TFF1 was associated with tumor size (p = 0.002), nodal status (p < 0.001), histological grade (p < 0.001), ER status (p = 0.012), PR status (p < 0.001) and HER2 (p < 0.001), while serum TFF1 was only statistically different among BC with ER+, PR + and HER2+ (p = 0.04139, 0.0018, 0.0004). Elevated TFF1 expression correlated with increased overall survival of BC patients (p = 0.00068). Finally, TFF1 was found to inhibit the cell growth, colony formation, migration and invasion of BC cells in vitro. All these results suggest that expression of TFF1 was related to ER status of BC and that expression of TFF1 was lower in TNBC than in non-TNBC. TFF1 was found to inhibit proliferation, migration and invasion of BC cells in vitro. Expression of TFF1 was associated with clinical characters of patients with BC. Serum TFF1 could be used to predict prognosis of patients with BC, especially non-TNBC.
Apolipoprotein C1 (APOC1) has been found to play an essential part in proliferation and metastasis of numerous cancers, but related mechanism has not been elucidated, especially its function and role ...in tumor immunity. Through systematic pan-cancer analysis, we identified that APOC1 was closely associated with the infiltration of various immune cells in multiple cancers. Besides, APOC1 was significantly co-expressed with the immune checkpoints, major histocompatibility complex (MHC) molecules, chemokines and other immune-related genes. Furthermore, single-cell sequencing analysis suggested that the vast majority of APOC1 was expressed in macrophages or tumor-associated macrophages (TAMs). Additionally, the expression of APOC1 was significantly related to the prognosis of different cancers. Since APOC1 was most significantly abnormally expressed in renal cell cancer (RCC), subsequent experiments were carried out in RCC to explore the role of APOC1 in tumor immunity. The expression of APOC1 was significantly elevated in the tumor and serum of RCC patients. Besides, APOC1 was mainly expressed in the macrophage and it was closely related to the immune cell infiltration of RCC. Co-culture with RCC cells could induce the generation of TAMs with M2 phenotype which be blocked by silencing APOC1. The expression of APOC1 was elevated in the M2 or TAMs and APOC1 promoted M2 polarization of macrophages through interacting with CD163 and CD206. Furthermore, macrophages overexpressing APOC1 promoted the metastasis of RCC cells via secreting CCL5. Together, these data indicate that APOC1 is an immunological biomarker which regulates macrophage polarization and promotes tumor metastasis.
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Glioblastoma multiforme (GBM) in the central nervous system is the most lethal advanced glioma and currently there is no effective treatment for it. Studies of sinomenine, an alkaloid from the ...Chinese medicinal plant, Sinomenium acutum, showed that it had inhibitory effects on several kinds of cancer. Here, we synthesized a sinomenine derivative, sino-wcj-33 (SW33), tested it for antitumor activity on GBM and explored the underlying mechanism. SW33 significantly inhibited proliferation and colony formation of GBM and reduced migration and invasion of U87 and U251 cells. It also arrested the cell cycle at G2/M phase and induced mitochondria-dependent apoptosis. Differential gene enrichment analysis and pathway validation showed that SW33 exerted anti-GBM effects by regulating PI3K/AKT and AMPK signaling pathways and significantly suppressed tumorigenicity with no obvious adverse effects on the body. SW33 also induced autophagy through the PI3K/AKT/mTOR and AMPK/mTOR pathways. Thus, SW33 appears to be a promising drug for treating GBM effectively and safely.
Sinomenine ester derivative SW33 significantly inhibited glioblastoma multiforme (GBM) by arresting cell cycle at G2/M phase, promoting apoptosis in mitochondria-dependent manner and inducing autophagy via PI3K/AKT/mTOR and AMPK/mTOR pathways with a good safety profile in vivo and in vitro. Display omitted
Colorectal cancer (CRC) is the third most common and the second most fatal cancer. In recent years, more attention has been directed toward the role of gut microbiota in the initiation and ...development of CRC. Some bacterial species, such as
,
,
,
, and
. have been associated with CRC, based upon sequencing studies in CRC patients and functional studies in cell culture and animal models. These bacteria can cause host DNA damage by genotoxic substances, including colibactin secreted by pks +
,
toxin (BFT) produced by
, and typhoid toxin (TT) from
. These bacteria can also indirectly promote CRC by influencing host-signaling pathways, such as E-cadherin/β-catenin, TLR4/MYD88/NF-κB, and SMO/RAS/p38 MAPK. Moreover, some of these bacteria can contribute to CRC progression by helping tumor cells to evade the immune response by suppressing immune cell function, creating a proinflammatory environment, or influencing the autophagy process. Treatments with the classical antibacterial drugs, metronidazole or erythromycin, the antibacterial active ingredients, M13@ Ag (electrostatically assembled from inorganic silver nanoparticles and the protein capsid of bacteriophage M13), berberine, and zerumbone, were found to inhibit tumorigenic bacteria to different degrees. In this review, we described progress in elucidating the tumorigenic mechanisms of several CRC-associated bacteria, as well as progress in developing effective antibacterial therapies. Specific bacteria have been shown to be active in the oncogenesis and progression of CRC, and some antibacterial compounds have shown therapeutic potential in bacteria-induced CRC. These bacteria may be useful as biomarkers or therapeutic targets for CRC.
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