Ferroptosis: Latest evidence and perspectives on plant-derived natural active compounds mitigating doxorubicin-induced cardiotoxicity.

Doxorubicin (DOX) is a chemotherapy drug widely used in clinical settings, acting as a first-line treatment for various malignant tumors. However, its use is greatly limited by the cardiotoxicity it induces, including doxorubicin-induced cardiomyopathy (DIC). The mechanisms behind DIC are not fully understood, but its potential biological mechanisms are thought to include oxidative stress, inflammation, energy metabolism disorders, mitochondrial damage, autophagy, apoptosis, and ferroptosis. Recent studies have shown that cardiac injury induced by DOX is closely related to ferroptosis. Due to their high efficacy, availability, and low side effects, natural medicine treatments hold strong clinical potential. Currently, natural medicines have been shown to mitigate DOX-induced ferroptosis and ease DIC through various functions such as antioxidation, iron ion homeostasis correction, lipid metabolism regulation, and mitochondrial function improvement. Therefore, this review summarizes the mechanisms of ferroptosis in DIC and the regulation by natural plant products, with the expectation of providing a reference for future research and development of inhibitors targeting ferroptosis in DIC. This review explores the mechanisms of ferroptosis in doxorubicin-induced cardiomyopathy (DIC) and summarizes how natural plant products can alleviate DIC by inhibiting ferroptosis through reducing oxidative stress, correcting iron ion homeostasis, regulating lipid metabolism, and improving mitochondrial function.

Biomarkers of heart failure: advances in omics studies.

Heart failure is a complex syndrome characterized by progressive circulatory dysfunction, manifesting clinically as pulmonary and systemic venous congestion, alongside inadequate tissue perfusion. The early identification of HF, particularly at the mild and moderate stages (stages B and C), presents a clinical challenge due to the overlap of signs, symptoms, and natriuretic peptide levels with other cardiorespiratory pathologies. Nonetheless, early detection coupled with timely pharmacological intervention is imperative for enhancing patient outcomes. Advances in high-throughput omics technologies have enabled researchers to analyze patient-derived biofluids and tissues, discovering biomarkers that are sensitive and specific for HF diagnosis. Due to the diversity of HF etiology, it is insufficient to study the diagnostic data of early HF using a single omics technology. This study reviewed the latest progress in genomics, transcriptomics, proteomics, and metabolomics for the identification of HF biomarkers, offering novel insights into the early clinical diagnosis of HF. However, the validity of biomarkers depends on the disease status, intervention time, genetic diversity and comorbidities of the subjects. Moreover, biomarkers lack generalizability in different clinical settings. Hence, it is imperative to conduct multi-center, large-scale and standardized clinical trials to enhance the diagnostic accuracy and utility of HF biomarkers.

ROCK2-RNA interaction map reveals multiple biological mechanisms underlying tumor progression in renal cell carcinoma.

Renal cell carcinoma (RCC) is the most common form of kidney cancer in adults. Despite new therapeutic modalities, the outcomes for RCC patients remain unsatisfactory. Rho-associated coiled-coil forming protein kinase 2 (ROCK2) has previously been shown to be upregulated in RCC, and its expression was negatively correlated with patient survival. However, the precise molecular function of ROCK2 has remained unclear. Herein, using RNA-seq analysis of ROCK2 knockdown and control cells, we identified 464 differentially expressed genes, and 1287 alternative splicing events in 786-O RCC cells. Furthermore, mapping of iRIP-seq reads in 786-O cells showed a biased distribution at 5' UTR, intronic and intergenic regions. By comparing ROCK2-regulated alternative splicing and iRIP-seq data, we found 292 overlapping genes that are enriched in multiple tumorigenic pathways. Taken together, our work defined a complex ROCK2-RNA interaction map on a genomic scale in a human RCC cell line, which deepens our understanding of the molecular function of ROCK2 in cancer development.

Morphological and Anatomical Analysis of the Internodes of a New Dwarf Variant of Moso Bamboo, Phyllostachys edulis f. exaurita.

The lack of mutants due to the long periods between flowering of bamboo plants is one of the limiting factors inhibiting research progress in the culm development of bamboo plants. In this study, a stable new dwarf variant of Phyllostachys edulis (Moso bamboo), Phyllostachys edulis f. exaurita T. G. Chen, was discovered and was characterized morphologically, anatomically, and physiologically. The height, diameter at breast height, number of internodes, length and wall thickness of internodes, length, width and number of parenchyma cells of internodes, and morphology of the wide-type (WT) and dwarf variant vascular bundles were compared. The height of the variant was only 49% that of the WT Moso bamboo. It was concluded that the decrease in internode number and length was the cause of dwarfism in P. edulis f. exaurita. The decreased internode length was the result of a decrease in cell number and cell length in the internode. In addition, the laws of change of internode length, internode thickness, cell length, and cell number differed between the WT Moso bamboo and the variant. Furthermore, lower IAA and zeatin concentrations were detected in the buds of the variant. These results suggest that P. edulis f. exaurita is a variant with inhibited primary thickening growth, which is valuable for interpretating the molecular mechanisms underlying the primary thickening growth of bamboo that are still largely unknown.

[Retracted] Oxidized­low density lipoprotein accumulates cholesterol esters via the PKCα­adipophilin­ACAT1 pathway in RAW264.7 cells.

Following the publication of the above paper, a concerned reader drew to the Editor's attention that the "con" and "ox­LDL" panels in Fig. 1E on p. 3602, and various data panels included in Figs. 3 and 5 on p. 3604, contained apparent anomalies, including what appeared to be matching patternings of cellular data either within the same figure panels or comparing among the data panels. After having conducted an independent investigation in the Editorial Office, the Editor of Molecular Medicine Reports has determined that the above paper should be retracted from the Journal on account of a lack of confidence in the overall authenticity of the data. After having consulted the authors in this regard, they agreed with the decision to retract this paper. The Editor deeply regrets any inconvenience that has been caused to the readership of the Journal. [Molecular Medicine Reports 12: 3599­3606, 2015; DOI: 10.3892/mmr.2015.3864.

PSMC6 induces immune cell infiltration and inflammatory response to aggravate primary Sjögren's syndrome.

Increasing evidence suggests that immune cell infiltration is involved in primary Sjögren's syndrome (pSS), while the underlying molecular mechanisms remain elusive. Herein, this study aims to explore the key molecular mechanism in immune cell infiltration in pSS based on Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were obtained, followed by weighted gene co-expression network analysis to acquire the pSS-related module genes. Moreover, pSS-related DEGs and module genes were intersected. Additionally, the correlation between key genes and immune cell infiltration was analyzed by CIBERSORT algorithm. Furthermore, pSS mouse models were established to explore the effects of PSMC6 on immune cell infiltration and inflammatory responses in pSS. A total of 51 DEGs and 334 key module genes were involved in the occurrence of pSS. The immune cell infiltration was correlated with pSS, and PSMC6, highly expressed in pSS samples, may be the key immune gene. In vivo animal experiments demonstrated that PSMC6 was upregulated in pSS, and PSMC6 knockdown could reduce lymphocytic infiltration in salivary glands and lacrimal glands and the levels of related inflammatory factors in the pSS and increase the proportion of Treg cells. Collectively, PSMC6 could induce immune cell infiltration and inflammatory responses to promote the occurrence of pSS, providing us with a potential therapeutic target for treating pSS.

Genome-Wide Identification, Expansion, and Evolution Analysis of Homeobox Gene Family Reveals TALE Genes Important for Secondary Cell Wall Biosynthesis in Moso Bamboo (Phyllostachys edulis).

The TALE gene family is a subfamily of the homeobox gene family and has been implicated in regulating plant secondary growth. However, reports about the evolutionary history and function of the TALE gene family in bamboo are limited. Here, the homeobox gene families of moso bamboo Olyra latifolia and Bonia amplexicaulis were identified and compared. Many duplication events and obvious expansions were found in the TALE family of woody bamboo. PhTALEs were found to have high syntenies with TALE genes in rice. Through gene co-expression analysis and quantitative real-time PCR analysis, the candidate PhTALEs were thought to be involved in regulating secondary cell wall development of moso bamboo during the fast-growing stage. Among these candidate PhTALEs, orthologs of OsKNAT7, OSH15, and SH5 in moso bamboo may regulate xylan synthesis by regulating the expression of IRX-like genes. These results suggested that PhTALEs may participate in the secondary cell wall deposition in internodes during the fast-growing stage of moso bamboo. The expansion of the TALE gene family may be implicated in the increased lignification of woody bamboo when divergent from herbaceous bamboos.

TRIP6 enhances stemness property of breast cancer cells through activation of Wnt/ß-catenin.

BACKGROUND: The urgent problem in the treatment of breast cancer is the recurrence induced by breast cancer stem cells (CSCs). Understanding the role and molecular mechanism of specific molecules in breast cancer stem cells can provide a theoretical basis for better treatment. TRIP6 is an adapter protein which belongs to the zyxin family of LIM proteins and is important in regulating the functions of CSCs. The present study aims to investigate the effects and mechanism of TRIP6 in breast cancer. METHODS: TRIP6 expression in breast cancer cells and tissues were detected by Real-Time PCR, western blot and immunohistochemistry (IHC). MTT assays, colony formation assays, Xenografted tumor model and mammosphere formation assays were performed to investigate the oncogenic functions of TRIP6 in the tumorigenic capability and the tumor-initiating cell-like phenotype of breast cancer cells in vitro and in vivo. Luciferase reporter, subcellular fractionation and immunofluorescence staining assays were performed to determine the underlying mechanism of TRIP6-mediated stemness of breast cancer cells. RESULTS: TRIP6 expression was significantly upregulated in breast cancer, and was closely related to the clinicopathologic characteristics, poor overall survival (OS), relapse-free survival (RFS) and poor prognosis of breast cancer patients. Functional studies revealed that overexpression of TRIP6 significantly enhanced proliferative, tumorigenicity capability and the cancer stem cell-like properties of breast cancer in vitro and in vivo. On the contrary, silencing TRIP6 achieved the opposite results. Notably, we found that TRIP6 promoted Wnt/ß-catenin signaling pathway in breast cancer to strengthen the tumor-initiating cell-like phenotype of breast cancer cells. CONCLUSIONS: This study indicates that TRIP6 plays an important role in maintaining the stem cell-like characteristics of breast cancer cells, supporting the significance of TRIP6 as a novel potential prognostic biomarker and therapeutic target for diagnosis and treatment of breast cancer.

The effect of CO rotation from shaped pulse polarization on reactions that form C2.

The effect of CO rotational energy on bimolecular reactions to form electronically excited C2 is reported here. The reactions are initiated by CO multiphoton absorption of 800 nm light in strong optical fields using two different polarization configurations based on shaped chirped pulses. The observation of Swan band emission indicates that C2(d3Πg) is a reaction product. The optical polarization is in the form of either an optical centrifuge or a dynamic polarization grating. In each case, the strong field aligns CO molecules and induces multiphoton absorption. Power-dependent measurements indicate at least seven photons are absorbed by CO; CO(a3Π) is a likely reactant candidate based on kinetic modeling. Relative reaction efficiencies are determined by measuring Swan band emission intensities. For a CO pressure of 100 Torr and an optical intensity of I = 2.0 × 1013 W cm-2, the relative C2(d3Πg) yield with the dynamic polarization grating is twice that with the optical centrifuge. The extent of CO rotational energy was determined for both optical polarizations using high-resolution transient IR absorption for a number of CO states with J = 62-73 and Erot up to 10 400 cm-1. Optical centrifuge excitation generates at least 2.5 times more rotationally excited CO molecules per quantum state than the dynamic polarization grating. The results indicate that the effect of large amounts of CO rotational energy is to reduce the yield of the C2 products.

Alkynyl carbon materials as novel and efficient sorbents for the adsorption of mercury(II) from wastewater.

For the first time, a series of alkynyl carbon materials (ACMs) were prepared via the mechanochemical reaction of CaC2 with six polyhalogenated precursors, namely CCl4, C2Cl6, C2Cl4, C6Cl6, C6Br6, and C14H4Br10 (ACM-1, ACM-2, ACM-3, ACM-4, ACM-5, and ACM-6, respectively) and used for the adsorptive removal of mercury from aqueous solutions. Based on preliminary investigations, the adsorption of mercury on ACM-5 was studied in depth. Specifically, the effect of pH on mercury adsorptivity, adsorption kinetics, thermodynamics, isotherms, and recyclability was studied. The adsorptivity of mercury on ACMs was found to be closely related to the hydrocarbon precursor, specific surface area of sorbent, and the alkynyl content. ACM-5 showed the best performance and is among the best raw carbonaceous sorbents reported so far, with a Langmuir saturated adsorption capacity of 191.9mgg-1. The promising mercury adsorption performance mainly arises from the strong Lewis soft acid-soft base interactions between the alkynyl groups and mercury ions. The adsorption isotherms could be satisfactorily correlated with the Langmuir equation. The results show that the ACMs can be used as efficient sorbents for the removal of mercury and may also be useful for the adsorption of other heavy metals.

High-accuracy 12C16O2 line intensities in the 2 µm wavelength region measured by frequency-stabilized cavity ring-down spectroscopy.

Reported here are highly accurate, experimentally measured ro-vibrational transition intensities for the R-branch of the (20012) - (00001) 12C16O2 band near λ = 2 µm. Measurements were performed by a frequency-stabilized cavity ring-down spectroscopy (FS-CRDS) instrument designed to achieve precision molecular spectroscopy in this important region of the infrared. Through careful control and traceable characterization of CO2 sample conditions, and through high-fidelity measurements spanning several months in time, we achieve relative standard uncertainties for the reported transition intensities between 0.15 % and 0.46 %. Such high accuracy spectroscopy is shown to provide a stringent test of calculated potential energy and ab initio dipole moment surfaces, and therefore transition intensities calculated from first principles.

Repression of Akt3 gene transcription by the tumor suppressor RIZ1.

RIZ1 has been studied as a tumor suppressor and may play a role in metabolic diseases related to the Western style diet, such as cancer and obesity. The Akt pathway is known to play a role in both cancer and obesity, and a link between Akt and RIZ1 has also been found. To better understand the role of RIZ1 in obesity and cancer, we investigated how RIZ1 regulates the expression of Akt3. We found that overexpression of RIZ1 in HEK293 cells reduced the expression of Akt3 protein. Luciferase reporter activity of Akt3 gene promoter was significantly reduced in cells co-transfected with RIZ1. Recombinant proteins of RIZ1 was able to bind the Akt3 promoter in vitro, and chromatin immunoprecipitation assay also demonstrated the ability of RIZ1 binding to the Akt3 promoter in vivo. Overexpression of RIZ1 increased H3K9 methylation on the Akt3 promoter. These results identify Akt3 as a target of RIZ1 regulation and expand our understanding of the Akt pathway in cancer and obesity.

Optical Measurement of Radiocarbon below Unity Fraction Modern by Linear Absorption Spectroscopy.

High-precision measurements of radiocarbon (14C) near or below a fraction modern 14C of 1 (F14C ≤ 1) are challenging and costly. An accurate, ultrasensitive linear absorption approach to detecting 14C would provide a simple and robust benchtop alternative to off-site accelerator mass spectrometry facilities. Here we report the quantitative measurement of 14C in gas-phase samples of CO2 with F14C < 1 using cavity ring-down spectroscopy in the linear absorption regime. Repeated analysis of CO2 derived from the combustion of either biogenic or petrogenic sources revealed a robust ability to differentiate samples with F14C < 1. With a combined uncertainty of 14C/12C = 130 fmol/mol (F14C = 0.11), initial performance of the calibration-free instrument is sufficient to investigate a variety of applications in radiocarbon measurement science including the study of biofuels and bioplastics, illicitly traded specimens, bomb dating, and atmospheric transport.

Synthesis and Supercapacitor Application of Alkynyl Carbon Materials Derived from CaC2 and Polyhalogenated Hydrocarbons by Interfacial Mechanochemical Reactions.

The discovery of new carbon materials and the reactive activation of CaC2 are challenging subjects. In this study, a series of alkynyl carbon materials (ACMs) were synthesized by the interfacial mechanochemical reaction of CaC2 with four typical polyhalogenated hydrocarbons. Their properties and structures were characterized, and their electrochemical performances were examined. The reaction was rapid and efficient arising from the intense mechanical activation of CaC2. The ACMs are micro-mesoporous materials with distinct layered structure, specific graphitization degree, and clear existence of sp-C. In addition, the ACMs exhibit high specific capacitance in the range of 57-133 F g-1 and thus can be ideal candidates for active materials used in supercapacitors. The results may imply an alternative synthesis of carbon allotropes, as well as an efficient approach for the activation of CaC2.

Efficient destruction of hexachlorobenzene by calcium carbide through mechanochemical reaction in a planetary ball mill.

Mechanochemical destruction (MCD) is a good alternative to traditional incineration for the destruction of persistent organic pollutants (POPs), like hexachlorobenzene (HCB), and the key is to find an efficient co-milling reagent. Toward this aim, HCB was milled with various reagents in a planetary ball mill at room temperature, and CaC2 was found to be the best one. HCB can be destroyed completely within 20 min at a mass ratio of CaC2/HCB = 0.9 and a rotation speed of 300 rpm. The ground samples were characterized by X-ray diffraction, X-ray photoelectron spectroscopy and Fourier transform infrared spectroscopy. The results show that the destruction products are nonhazardous CaCl2 and carbon material with both crystalline and amorphous structures. On these bases, possible reaction pathways were proposed. Considering its excellent efficiency and safety, CaC2 may be the most feasible co-milling regent for MCD treatment of HCB. Further, the results are instructive for the destruction of other POPs.

Impulsive Collision Dynamics of CO Super Rotors from an Optical Centrifuge.

We report state-resolved collision dynamics for CO molecules prepared in an optical centrifuge and measured with high-resolution transient IR absorption spectroscopy. Time-resolved polarization-sensitive measurements of excited CO molecules in the J=29 rotational state reveal that the oriented angular momentum of CO rotors is relaxed by impulsive collisions. The translational energy gains for molecules in the initial plane of rotation are threefold larger than for randomized angular momentum orientations, indicating the presence of anisotropic kinetic energy. The transient data show enhanced population for CO molecules in the initial plane of rotation immediately following the optical centrifuge pulse. A comparison with previous CO2 super rotor studies illustrates the behavior of molecular gyroscopes; spatial reorientation of CO2 J=76 rotors takes substantially longer than that for CO J=29 rotors, despite similarities in classical rotational period and rotational energy gap. High-resolution transient IR absorption measurements of the CO J=29-39 rotational states show that the collisional depopulation rates increase with J quantum number.

Precision Interferometric Measurements of Mirror Birefringence in High-Finesse Optical Resonators.

High-finesse optical resonators found in ultrasensitive laser spectrometers utilize supermirrors ideally consisting of isotropic high-reflectivity coatings. Strictly speaking, however, the optical coatings are often non-uniformly stressed during the deposition process and therefore do possess some small amount of birefringence. When physically mounted the cavity mirrors can be additionally stressed in such a way that large optical birefringence is induced. Here we report a direct measurement of optical birefringence in a two-mirror Fabry-Pérot cavity with R = 99.99 % by observing TEM00 mode beating during cavity decays. Experiments were performed at a wavelength of 4.53 µm, with precision limited by both quantum and technical noise sources. We report a splitting of δν = 618(1) Hz, significantly less than the intrinsic cavity linewidth of δcav ≈ 3 kHz. With a cavity free spectral range of 96.9 MHz, the equivalent fractional change in mirror refractive index due to birefringence is therefore Δn/n = 6.38(1) × 10-6.

State-Specific Collision Dynamics of Molecular Super Rotors with Oriented Angular Momentum.

An optical centrifuge pulse drives carbon dioxide molecules into ultrahigh rotational states with rotational frequencies of ω ≈ 32 THz based on the centrifuge frequency at the full width at half-maximum of the spectral chirp. High-resolution transient IR absorption spectroscopy is used to measure the time-evolution of translational and rotational energy for a number of states in the range of J = 0-100 at a sample pressure of 5-10 Torr. Transient Doppler profiles show that the products of super rotor collisions contain substantial amounts of translational energy, with J-dependent energies correlating to a range of ΔJ propensities. The transient population in J = 100 is short-lived, indicating rapid relaxation of high J states; populations in J = 36, 54, and 76 increase overall as the super rotor energy is redistributed. Transient line profiles for J = 0 and 36 are consistently narrower than the initial ambient sample temperature, showing that collision cross sections for super rotors increase with decreasing collision energy. Quantum scattering calculations on Ar-CO2(j) collisions are used to interpret the qualitative features of the experimental results. The results of this study provide the groundwork for developing a more complete understanding of super rotor dynamics.

Oxidized-low density lipoprotein accumulates cholesterol esters via the PKCα-adipophilin-ACAT1 pathway in RAW264.7 cells.

Oxidized low­density lipoprotein (ox­LDL) can increase the expression of adipophilin and the accumulation of intracellular lipid droplets. However, the detailed mechanisms remain to be fully elucidated. The present study aimed to investigate the mechanism underlying the effect of ox­LDL on the expression of adipophilin and the accumulation of intracellular cholesterol esters. The results revealed that ox­LDL increased the activation of protein kinase C α (PKCα), expression of adipophilin and acyl­coenzymeA: cholesterol acyltransferse 1 (ACAT1) and increased accumulation of intracellular cholesterol esters. In addition, PKCα siRNA abrogated ox­LDL­induced adipophilin, expression of ATAC1 and accumulation of cholesterol esters. Furthermore, ox­LDL increased the accumulation of intracellular cholesterol esters and expression of ACAT1, and this effect were reversed by transfection with adipophilin siRNA. Taken together, these results demonstrated that ox­LDL induces the accumulation of cholesterol esters, which is mediated by the PKCα­adipophilin­ACAT1 pathway.

Oxidized low-density lipoprotein activates adipophilin through ERK1/2 signal pathway in RAW264.7 cells.

It has been reported that oxidized low-density lipoprotein (Ox-LDL) can increase the expression of adipophilin. However, the detailed mechanisms are not fully understood. The aim of this study was to investigate the mechanism of Ox-LDL on adipophilin expression and the intracellular lipid droplet accumulation. A mouse macrophage-like cell line, RAW264.7, was used throughout, and it was found that Ox-LDL induced adipophilin expression in a dose-dependent manner. Moreover, Ox-LDL induced peroxisome proliferator-activated receptor-gamma (PPARgamma) expression and PPARgamma-specific inhibitor T0070907 abrogated Ox-LDL-induced adipophilin expression, but specific agonist GW1929 not. Furthermore, Ox-LDL induced phosphorylation of ERK1/2, and ERK1/2-specific inhibition by PD98059 suppressed the Ox-LDL-induced PPARgamma and adipophilin expression. The results showed that ERK1/2 or PPARgamma-specific inhibition decreased the amounts of intracellular lipid droplets. Meanwhile, the PPARgamma-specific agonist increased intracellular lipid droplets. These results suggested that Ox-LDL-induced increase in adipophilin level via ERK1/2 activation is one of the mechanisms of inducing greater amounts of intracellular lipid droplets in RAW264.7 cells, which indicated that adipophilin is involved in atherosclerotic progression.