Increased risk of colorectal cancer (CRC) is associated with altered intestinal microbiota as well as short‐chain fatty acids (SCFAs) reduction of output The energy source of colon cells relies ...mainly on three SCFAs, namely butyrate (BT), propionate, and acetate, while CRC transformed cells rely mainly on aerobic glycolysis to provide energy. This review summarizes recent research results for dysregulated glucose metabolism of SCFAs, which could be initiated by gut microbiome of CRC. Moreover, the relationship between SCFA transporters and glycolysis, which may correlate with the initiation and progression of CRC, are also discussed. Additionally, this review explores the linkage of BT to transport of SCFAs expressions between normal and cancerous colonocyte cell growth for tumorigenesis inhibition in CRC. Furthermore, the link between gut microbiota and SCFAs in the metabolism of CRC, in addition, the proteins and genes related to SCFAs‐mediated signaling pathways, coupled with their correlation with the initiation and progression of CRC are also discussed. Therefore, targeting the SCFA transporters to regulate lactate generation and export of BT, as well as applying SCFAs or gut microbiota and natural compounds for chemoprevention may be clinically useful for CRCs treatment. Future research should focus on the combination these therapeutic agents with metabolic inhibitors to effectively target the tumor SCFAs and regulate the bacterial ecology for activation of potent anticancer effect, which may provide more effective application prospect for CRC therapy.
Short‐chain fatty acids (SCFAs) produced in the human colon are the major products of bacterial fermentation of undigested dietary fiber and starch that escape absorption in the small intestine, and serve as a major source of energy for colonocytes. SCFAs are microbial‐derived metabolites, which are readily absorbed and used as an energy source by colonocytes. Several mechanisms have been proposed to underlie the anticancerous mechanisms of SCFAs. SCFAs reduce epithelial inflammation and trigger cancer cell apoptosis via p21 activity, providing an important defensive capacity against colorectal carcinogenesis.
In elderly people particularly in postmenopausal women, inadequate bone formation by osteoblasts originating from bone marrow mesenchymal stem cells (BMSCs) for compensation of bone resorption by ...osteoclasts is a major reason for osteoporosis. Enhancing osteoblastic differentiation of BMSCs is a feasible therapeutic strategy for osteoporosis. Here, bone marrow stromal cell (ST)-derived exosomes (STExos) are found to remarkably enhance osteoblastic differentiation of BMSCs in vitro. However, intravenous injection of STExos is inefficient in ameliorating osteoporotic phenotypes in an ovariectomy (OVX)-induced postmenopausal osteoporosis mouse model, which may be because STExos are predominantly accumulated in the liver and lungs, but not in bone. Hereby, the STExo surface is conjugated with a BMSC-specific aptamer, which delivers STExos into BMSCs within bone marrow. Intravenous injection of the STExo-Aptamer complex enhances bone mass in OVX mice and accelerates bone healing in a femur fracture mouse model. These results demonstrate the efficiency of BMSC-specific aptamer-functionalized STExos in targeting bone to promote bone regeneration, providing a novel promising approach for the treatment of osteoporosis and fracture.
Colorectal cancer (CRC) is a heterogeneous group of diseases that are the result of abnormal glucose metabolism alterations with high lactate production by pyruvate to lactate conversion, which ...remodels acidosis and offers an evolutional advantage for tumor cells, even enhancing their aggressive phenotype. This review summarizes recent findings that involve multiple genes, molecules, and downstream signaling in the dysregulated glycolytic pathway, which can allow a tumor to initiate acid byproducts and to progress, thereby resulting in acidosis commonly found in the tumor microenvironment of CRC. Moreover, the relationship between CRC cells and the tumor acidic microenvironment, especially for regulating lactate production and lactate dehydrogenase A levels, is also discussed, as well as comprehensively defining different aspects of glycolytic pathways that affect cancer cell proliferation, invasion, and migration. Furthermore, this review concentrates on glucose metabolism–mediated transduction factors in CRC, which include acid‐sensing ion channels, triosephosphate isomerase and key glycolysis‐related enzymes that regulate glycolytic metabolites, coupled with the effect on tumor cell glycolysis as well as signaling pathways. In conclusion, glucose metabolism mediated by glycolytic pathways that are integral to tumor acidosis in CRC is demonstrated. Therefore, selective metabolic inhibitors or agents against these targets in glucose metabolism through glycolytic pathways may be clinically useful to regulate the tumor’s acidic microenvironment for CRC treatment and to identify specific targets that regulate tumor acidosis through a cancer patient–personalized approach. Furthermore, strategies for modifying the metabolic processes that effectively inhibit cancer cell growth and tumor progression and activate potent anticancer effects may provide more effective antitumor prospects for CRC therapy.
Glucose metabolism mediated by glycolytic pathways that are integral to tumor acidosis in colorectal cancer is demonstrated. Therefore, selective metabolic inhibitors or agents against these targets in glucose metabolism through glycolytic pathways may be clinically useful to regulate the tumor’s acidic microenvironment for colorectal cancer treatment and to identify specific targets that regulate tumor acidosis through a cancer patient–personalized approach.
Glioblastoma multiforme (GBM) is the most malignant and aggressive glioma with abnormal expression of genes that mediate glycolytic metabolism and tumor cell growth. Petunidin‐3‐O‐glucoside (Pt3glc) ...is a kind of anthocyanin in the red grape and derived beverages, representing the most common naturally occurring anthocyanins with a reduced incidence of cancer and heart diseases. In this study, whether Pt3glc could effectively regulate glycolysis to inhibit GBM cell was investigated by using the DBTRG‐05MG cell lines. Notably, Pt3glc displayed potent antiproliferative activity and significantly changed the protein levels related to both glycolytic metabolism and GBM cell survival. The expression of the proapoptotic protein Bcl‐2‐associated X protein was increased with concomitant reduction on the levels of the antiapoptotic protein B‐cell lymphoma 2 and caspase‐3 activity. Furthermore, the levels of survival signaling proteins, such as protein kinase B (Akt) and phospho‐Akt (Scr473), extracellular signal‐regulated kinase (ERK) and phospho‐ERK, were significantly decreased by Pt3glc in combination with the phosphoinositide 3‐kinase (PI3K) inhibitor of LY294002. Most importantly, the levels of Sirtuin 3 (SIRT3) and phosphorylated p53 were also downregulated, indicating that Pt3glc combinated with PI3K inhibitor could induce GBM cell death may act via the SIRT3/p53‐mediated mitochondrial and PI3K/Akt‐ERK pathways. Our findings thus provide rational evidence that the combination of Pt3glc with PI3K inhibitor, which target alternative pathways in GBM cells, may be a useful adjuvant therapy in glioblastoma treatment.
The possible interactions between different signaling pathways in glioblastoma cells treated with Pt3glc, which inhibited glioblastoma cell proliferation and promote apoptosis by regulating the expression of SIRT3 and down‐regulating the p53 through ROS/p53‐mediated mitochondrial pathway via SIRT3. The combination of Pt3glc with LY294002 could produce the synergistic effect to inhibit the SIRT3‐mediated glycolytic as well as regulation of mTOR/Akt pathway. Pt3glc appears to play a central role in regulating SIRT3 for glioblastoma cell death, thus qualifies as a potential target for anti‐cancer treatment.
Adipocyte differentiation of bone marrow mesenchymal stem/stromal cells (BMSCs) instead of osteoblast formation contributes to age- and menopause-related marrow adiposity and osteoporosis. Vascular ...calcification often occurs with osteoporosis, a contradictory association called "calcification paradox". Here we show that extracellular vesicles derived from aged bone matrix (AB-EVs) during bone resorption favor BMSC adipogenesis rather than osteogenesis and augment calcification of vascular smooth muscle cells. Intravenous or intramedullary injection of AB-EVs promotes bone-fat imbalance and exacerbates Vitamin D3 (VD3)-induced vascular calcification in young or old mice. Alendronate (ALE), a bone resorption inhibitor, down-regulates AB-EVs release and attenuates aging- and ovariectomy-induced bone-fat imbalance. In the VD3-treated aged mice, ALE suppresses the ovariectomy-induced aggravation of vascular calcification. MiR-483-5p and miR-2861 are enriched in AB-EVs and essential for the AB-EVs-induced bone-fat imbalance and exacerbation of vascular calcification. Our study uncovers the role of AB-EVs as a messenger for calcification paradox by transferring miR-483-5p and miR-2861.
Transcription factors (TFs) like a nuclear factor of activated T‐cells (NFAT) and its controller calcineurin are highly expressed in primary intestinal epithelial cells (IECs) due to delamination, ...damage by tumor‐associated flora and selective activation in the intestinal tract tumor are crucial in the progression and growth of colorectal cancer (CRC). This study sought to summarize the current findings concerning the dysregulated calcineurin/NFAT (C/N) signaling involved in CRC initiation and progression. These signalings include proliferation, T‐cell functions, and glycolysis with high lactate production that remodels the acidosis, which genes in tumor cells provide an evolutionary advantage, or even increased their attack phenotype. Moreover, the relationship between C/N and gut microbiome in CRC, especially role of NFAT and toll‐like receptor signaling in regulating intestinal microbiota are also discussed. Furthermore, this review will discuss the proteins and genes relating to C/N induced acidosis in CRC, which includes ASIC2 regulated C/N1 and TFs associated with the glycolytic by‐product that affect T‐cell functions and CRC cell growth. It is revealed that calcineurin or NFAT targeting to antitumor, selective calcineurin inhibition or targets in NFAT signaling may be useful for clinical treatment of CRC. This can further aid in the identification of specific targets via cancer patient‐personalized approach. Future studies should be focused on targeting to C/N or TLR signaling by the combination of therapeutic agents to regulate T‐cell functions and gut microbiome for activating potent anticancer property with the prospect of potentiating the antitumor therapy for CRC.
The link between T‐cells perform glycolysis and ASICs–mediated acidosis signaling in colorectal cancer. Roles of calcineurin/nuclear factor of activated T‐cells and toll‐like receptor signaling altered tumor‐associated microbiota in the development of an intestinal tumor.
Abstract Asteroseismology offers a profound window into stellar interiors and has emerged as a pivotal technique in exoplanetary research. This study harnesses the Transiting Exoplanet Survey ...Satellite observations to reveal, for the first time, the asteroseismic oscillations of four exoplanet-hosting stars. Through meticulous analysis, we extracted their asteroseismic signatures, enabling the precise determination of stellar masses, radii, luminosities, and surface gravities. These parameters exhibit markedly reduced uncertainties compared to those derived from spectroscopic methods. Crucially, the exoplanets orbiting these stars were initially identified via radial velocity measurements. The refinement of host stellar masses necessitates a corresponding adjustment in planetary characteristics. Employing asteroseismology, we recalibrated the exoplanets’ minimum masses and semimajor axes—a novel approach in the field. For instance, the exoplanet HD 5608 b's minimum mass, denoted as M sin i , was ascertained to be 1.421 ± 0.091 M J through the integration of asteroseismic and radial velocity data. Similarly, two planets within the 7 CMa system yielded M sin i values of 1.940 ± 0.064 M J and 0.912 ± 0.067 M J , respectively. Two planets in the HD 33844 system presented M sin i figures of 1.726 ± 0.145 M J and 1.541 ± 0.182 M J , while the HIP 67851 system's planets registered M sin i at 1.243 ± 0.139 M J and a notably higher 5.387 ± 0.699 M J . This investigation extends beyond mere parameter refinement, it underscores the synergy between asteroseismology and exoplanetology, yielding unprecedented precision in system metrics. Focusing on a quartet of K-type giants in advanced evolutionary phases, our work positions these systems as invaluable astrophysical laboratories, offering insights into the potential trajectory of our own solar system's fate.
Abstract
Heartbeat stars (HBSs) with tidally excited oscillations (TEOs) are ideal laboratories for studying the effect of equilibrium and dynamical tides. However, studies of TEOs in Kepler HBSs are ...rare due to the need for better modeling of the equilibrium tide in light curves. We revisit the HBSs in our previous work and study the TEOs in these HBSs based on the derived orbital parameters that could express the equilibrium tide. We also compile a set of analytic procedures to examine the harmonic and anharmonic TEOs in their Fourier spectra. The TEOs of 21 HBSs have been newly analyzed and presented. Twelve of these HBSs show prominent TEOs (signal-to-noise ratio of the harmonics S/N ≥ 10). The relation between the orbital eccentricities and the harmonic number of the TEOs shows a positive correlation. The relation between the orbital periods and the harmonic number also shows a positive correlation. Furthermore, the distribution of HBSs with TEOs in the Hertzsprung–Russell diagram shows that TEOs are more visible in hot stars with surface effective temperatures
T
≳ 6500 K. These samples may also be valuable targets for future studies of the effect of tidal action in eccentric orbits.
Abstract TV Col is a long-period eclipsing intermediate polar (IP) prototype star for the negative superhump (NSH) system. We investigate the eclipse minima, eclipse depth, and NSH amplitude based on ...TESS photometry. Using the same analytical method as for SDSS J081256.85+191157.8, we find periodic variations of O − C for eclipse minima and NSH amplitudes with periods of 3.939(25) days and 3.907(30) days, respectively. The periodic variation of the NSH amplitude of TV Col confirms that periodic changes in NSH amplitude in response to the tilted disk precession may be universal, which is further evidence that the origin of the NSHs is related to the tilted disk precession. We suggest that the variation in NSH amplitude may be similar to the superorbital signal, coming from the periodic change in visual brightness of the energy released by streams touching the tilted disk with tilted disk precession. Finally, we find for the first time that the eclipse depth exhibits biperiodic variations with periods of P 1 = 3.905(11) days and P 2 = 1.953(4) days, respectively. P 2 is about half of P 1 and the disk precession period ( P 1 ≈ P prec ≈ 2 × P 2 ). We suggest that P 1 may come from the periodic change in the brightness of the eclipse center due to tilted disk precession, while P 2 may come from two accretion curtains precessing together with the tilted disk, but more verification and discussion are necessary. The discovery of biperiodic variations in eclipse depth provides a new window for studying IPs and tilted disk precession.
Abstract
Negative superhumps (NSHs) are signals a few percent shorter than the orbital period of a binary star and are considered to originate from the reverse precession of the tilted disk. Based on ...TESS photometry, we find nine new cataclysmic variable stars with NSHs. Three (ASAS J1420, TZ Per, and V392 Hya) of these stars similar to AH Her still have NSHs during dwarf nova outbursts, and the NSH amplitude varies with the outburst. The variation in the radius of the accretion disk partially explains this phenomenon. However, it does not explain the rebound of the NSH amplitude after the peak of the outburst and the fact that the NSH amplitude of the quiescence is sometimes not the largest, and it is necessary to include the disk instability model (DIM) and add other ingredients. Therefore, we suggest that the variation of NSH amplitude with outburst can be an important basis for studying the origin of NSHs and improving the DIM. The six (ASASSN-V J1137, ASASSN-V J0611, 2MASS J0715, LAMOST J0925, ASASSN-17qj, and ZTF 18acakuxo) remaining stars have been poorly studied, and for the first time we determine their orbital periods, NSHs, and superorbital signal (SOR) periods. The NSH periods and amplitudes of ASASSN-V J1137 and ASASSN-17qj vary with the SOR, and based on the comparison of the observations with the theory, we suggest that a single change in tilted disk angle does not explain the observations of the SOR and that other ingredients need to be considered as well.
