Reciprocal modulation of long noncoding RNA EMS and p53 regulates tumorigenesis.

p53 plays a central role in tumor suppression. Emerging evidence suggests long noncoding RNA (lncRNA) as an important class of regulatory molecules that control the p53 signaling. Here, we report that the oncogenic lncRNA E2F1 messenger RNA (mRNA) stabilizing factor (EMS) and p53 mutually repress each other's expression. EMS is negatively regulated by p53. As a direct transcriptional repression target of p53, EMS is surprisingly shown to inhibit p53 expression. EMS associates with cytoplasmic polyadenylation element-binding protein 2 (CPEB2) and thus, disrupts the CPEB2-p53 mRNA interaction. This disassociation attenuates CPEB2-mediated p53 mRNA polyadenylation and suppresses p53 translation. Functionally, EMS is able to exert its oncogenic activities, at least partially, via the CPEB2-p53 axis. Together, these findings reveal a double-negative feedback loop between p53 and EMS, through which p53 is finely controlled. Our study also demonstrates a critical role for EMS in promoting tumorigenesis via the negative regulation of p53.

A new direction in periodontitis treatment: biomaterial-mediated macrophage immunotherapy.

Periodontitis is a chronic inflammation caused by a bacterial infection and is intimately associated with an overactive immune response. Biomaterials are being utilized more frequently in periodontal therapy due to their designability and unique drug delivery system. However, local and systemic immune response reactions driven by the implantation of biomaterials could result in inflammation, tissue damage, and fibrosis, which could end up with the failure of the implantation. Therefore, immunological adjustment of biomaterials through precise design can reduce the host reaction while eliminating the periodontal tissue's long-term chronic inflammation response. It is important to note that macrophages are an active immune system component that can participate in the progression of periodontal disease through intricate polarization mechanisms. And modulating macrophage polarization by designing biomaterials has emerged as a new periodontal therapy technique. In this review, we discuss the role of macrophages in periodontitis and typical strategies for polarizing macrophages with biomaterials. Subsequently, we discuss the challenges and potential opportunities of using biomaterials to manipulate periodontal macrophages to facilitate periodontal regeneration.

Association of daily sitting time and coffee consumption with the risk of all-cause and cardiovascular disease mortality among US adults.

BACKGROUND: Sedentary behavior has been demonstrated to be a modifiable factor for several chronic diseases, while coffee consumption is believed to be beneficial for health. However, the joint associations of daily sitting time and coffee consumption with mortality remains poorly understood. This study aimed to evaluate the independent and joint associations of daily sitting time and coffee intakes with mortality from all-cause and cardiovascular disease (CVD) among US adults. METHODS: An analysis of a prospective cohort from the 2007-2018 National Health and Nutrition Examination Survey of US adults (n = 10,639). Data on mortality were compiled from interview and physical examination data until December 31, 2019. Daily sitting time was self-reported. Coffee beverages were from the 24-hour diet recall interview. The main outcomes of the study were all-cause and cardiovascular disease mortality. The adjusted hazard ratios [HRs] and 95% confidence intervals [CI] were imputed by Cox proportional hazards regression. RESULTS: Among 10,639 participants in the study cohort, there were 945 deaths, 284 of whom died of CVD during the follow-up period of up to 13 years. Multivariable models showed that sitting more than 8 h/d was associated with higher risks of all-cause (HR, 1.46; 95% CI, 1.17-1.81) and CVD (HR, 1.79; 95% CI, 1.21-2.66) mortality, compared with those sitting for less than 4 h/d. People with the highest quartile of coffee consumption were observed for the reduced risks of both all-cause (HR, 0.67; 95% CI, 0.54-0.84) and CVD (HR, 0.46; 95% CI, 0.30-0.69) mortality compared with non-coffee consumers. Notably, joint analyses firstly showed that non-coffee drinkers who sat six hours or more per day were 1.58 (95% CI, 1.25-1.99) times more likely to die of all causes than coffee drinkers sitting for less than six hours per day, indicating that the association of sedentary with increased mortality was only observed among adults with no coffee consumption but not among those who had coffee intake. CONCLUSIONS: This study identified that sedentary behavior for more than 6 h/d accompanied with non-coffee consumption, were strongly associated with the increased risk of mortality from all-cause and CVD.

A water quality assessment model involving novel fluorescence technology.

The reasonable utilization of water resources and real-time monitoring of water pollution are the core tasks of current world hydrological and water conservancy work. Novel technologies and methods for monitoring water pollution are important means to ensure water health. However, the absence of intuitive and simple analysis methods for the assessment of regional pollution in large-scale water bodies has prevented scientists from quickly grasping the overall situation of water pollution. In this study, we propose a strategy based on the unique combination of fluorescence technology and simple kriging (SK) interpolation (FL-SK) for the first time. This strategy could present the relative magnitude and distribution of the physicochemical indicators of a whole natural lake intuitively and accurately. The unique FL-SK model firstly offers a simple and effective water quality method that provides the pollution index of different sampling points in lakes. The macroscopic evaluation of large-scale water bodies by the FL-SK model primarily relies on the fluorescence response of the RDM-TPE to the comprehensive indicators of the water body, as experimental results have revealed a good correlation between fluorescent responses and six normalized physicochemical indicators. Multiple linear regression and fluorescence response experiments on RDM-TPE indicate that to some extent, the fluorescence signals of the FL-SK model may originate from a certain type of sulfide in the water body. Pattern discovery could enable the analysis of pollution levels in other ecosystems and promote early pollution assessment in the future.

Visualization Tools for Detecting Microcystin-LR in the Biological System via Near-Infrared Fluorescent Probes.

Numerous toxicological and epidemiological studies have shown that microcystin-LR (MC-LR) could cause a variety of toxicity to humans and animals. However, the absence of effective methods to trace MC-LR in biological systems has hindered the in-depth understanding of the mechanism of MC-LR toxicity. Near-infrared (NIR) fluorescent probes are crucial tools for accurate visualization and in-depth study of specific molecules in biological systems. Due to the lack of effective design strategies, NIR fluorescent probes for imaging MC-LR specifically in biological systems have not been reported yet. In order to address this pressing issue, herein, we have introduced a new and facile strategy to improve MC-LR detection and imaging in biological systems, and based on this design strategy, three NIR fluorescence probes (MC-RdTPA1, MC-RdTPA2, and MC-RdTPE1) have been constructed. These probes have several advantages: (i) have long emission wavelength and large Stokes shifts, which have great potential in vivo imaging applications; (ii) could selectively visualize MC-LR in cells; and (iii) showed stable fluorescence intensity in the pH range of 5.0-7.0. This work may provide a new avenue for the detection of MC-LR in biological systems and new tool to advance our knowledge of the mechanism of MC-LR toxicity.

Boosting Microwave Thermo-Dynamic Cancer Therapy of TiMOF via COF-Coating.

Microwave (MW) dynamic therapy (MDT) can efficiently eliminate tumor residue resulting from MW thermal therapy. However, MDT is currently in its infancy, and luck of effective MDT sensiters severely limits its clinical therapeutic effect. Herein, based on TiMOF (TM), a high-efficiency MW sensitizer is designed for MW thermo-dynamic therapy. TM can generate heat and cytotoxic reacyive oxygen species (ROS) under MW irradiation and has the potential to be used as an MW sensitizer, while the suboptimal MW dynamic sensitization effect of TM limits its application. Inorder to improve the MW dynamic sensitization performance, a covalent organic framework (COF) with good stability and a large conjugate system is used to cover TM, which is conductive to electron and energy transfer, thus increasing the ROS generation rate and prolonging the ROS lifetime. In addition, loading Ni NPs endow nanomaterials with magnetic resonance imaging capabilities. Therefore, this work develops an MW sensitizer based on TM for the first time, and the mechanism of COF coating to enhance the MW dynamic sensitization of TM is preliminarily explored, which provides a new idea for the further development of MW sensitizer with great potential.

Identification and clinical significance of tsRNAs and miRNAs in PBMCs of treatment-requiring retinopathy of prematurity.

The aim of the study is to reveal the expression profiling and clinical significance of peripheral blood mononuclear cell (PBMC) tRNA-derived small RNAs (tsRNAs) and microRNAs (miRNAs) of premature infants with treatment-requiring retinopathy of prematurity (ROP). Significantly altered tsRNAs and miRNAs were screened using small RNA sequencing. RT-qPCR was used to verify the altered RNAs identified by small RNA transcriptomics. The target genes, their enriched functions, and possibly involved signaling pathways were identified by bioinformatics analyses. According to the small RNA sequencing, 125 tsRNAs and 205 miRNAs were significantly altered in PBMCs obtained from infants with treatment-requiring ROP compared with the premature controls without retinopathy. We preliminarily validated the significant alterations of 6 tsRNAs and 9 miRNAs. The target genes for those tsRNAs were enriched for cellular macromolecule metabolic process, intracellular anatomical structure, transcription regulatory region nucleic acid binding, and Th17 cell differentiation; those of the altered miRNAs were enriched for the developmental process, cell junction, DNA-binding transcription activator activity, and FoxO signaling pathway. By verification with the extended sample size, we identified tsRNAs and miRNAs that could be potential biomarkers with clinical values. The study recognized the alterations and clinical significance of changed tsRNA/miRNA profiles in PBMCs from premature infants with ROP. These significantly altered tsRNAs and miRNAs might be useful as potential diagnostic biomarkers and molecular targets for treatment-requiring ROP.

m6A modifications of circular RNAs in ischemia-induced retinal neovascularization.

Ischemia-induced pathological neovascularization in the retina is a leading cause of blindness in various age groups. The purpose of the current study was to identify the involvement of circular RNAs (circRNAs) methylated by N6-methyladenosine (m6A), and predict their potential roles in oxygen-induced retinopathy (OIR) in mice. Methylation assessment via microarray analysis indicated that 88 circRNAs were differentially modified by m6A methylation, including 56 hyper-methylated circRNAs and 32 hypo-methylated circRNAs. Gene ontology enrichment analysis predicted that the enriched host genes of the hyper-methylated circRNAs were involved in cellular process, cellular anatomical entity, and protein binding. Host genes of the hypo-methylated circRNAs were enriched in the regulation of cellular biosynthetic process, the nucleus, and binding. According to the Kyoto Encyclopedia of Genes and Genomes analysis, those host genes were involved in the pathways of selenocompound metabolism, salivary secretion, and lysine degradation. MeRIP-qPCR verified significant alterations in m6A methylation levels of mmu_circRNA_33363, mmu_circRNA_002816, and mmu_circRNA_009692. In conclusion, the study revealed the m6A modification alterations in OIR retinas, and the findings above shed light on the potential roles of m6A methylation in circRNA regulatory functions in the pathogenesis of ischemia-induced pathological retinal neovascularization.

Mesenchymal stem cells-derived extracellular vesicles protect against oxidative stress-induced xenogeneic biological root injury via adaptive regulation of the PI3K/Akt/NRF2 pathway.

Xenogeneic extracellular matrices (xECM) for cell support have emerged as a potential strategy for addressing the scarcity of donor matrices for allotransplantation. However, the poor survival rate or failure of xECM-based organ transplantation is due to the negative impacts of high-level oxidative stress and inflammation on seed cell viability and stemness. Herein, we constructed xenogeneic bioengineered tooth roots (bio-roots) and used extracellular vesicles from human adipose-derived mesenchymal stem cells (hASC-EVs) to shield bio-roots from oxidative damage. Pretreatment with hASC-EVs reduced cell apoptosis, reactive oxygen species generation, mitochondrial changes, and DNA damage. Furthermore, hASC-EV treatment improved cell proliferation, antioxidant capacity, and odontogenic and osteogenic differentiation, while significantly suppressing oxidative damage by activating the phosphatidylinositol 3-kinase (PI3K)/Akt pathway and nuclear factor erythroid 2 (NFE2)-related factor 2 (NRF2) nuclear translocation via p62-associated Kelch-like ECH-associated protein 1 (KEAP1) degradation. Inhibition of PI3K/Akt and Nrf2 knockdown reduced antioxidant capacity, indicating that the PI3K/Akt/NRF2 pathway partly mediates these effects. In subcutaneous grafting experiments using Sprague-Dawley rats, hASC-EV administration significantly enhanced the antioxidant effect of the bio-root, improved the regeneration efficiency of periodontal ligament-like tissue, and maximized xenograft function. Conclusively, therefore, hASC-EVs have the potential to be used as an immune modulator and antioxidant for treating oxidative stress-induced bio-root resorption and degradation, which may be utilized for the generation and restoration of other intricate tissues and organs.

Feedback of lake trophic status via MC-LR fluorescence technique.

Eutrophication remains one of the most challenging environmental problems, and microcystin-leucine-arginine (MC-LR) produced in eutrophic waters would cause serious ecological risks. However, the traditional assessment methods of trophic status, such as water quality index (WQI) and trophic status index (TSI), could not directly reflect the existence or concentration of MC-LR in water. Moreover, traditional MC-LR detection methods are costly and time-consuming. Therefore, it remains a challenge to develop a method that can simply and quickly reflect the level of MC-LR. Herein, a novel probe with specific response to MC-LR was proposed to assess the distribution characteristics of MC-LR in water bodies. By combining the response signal of the probe with the filtered water sample and the water quality parameters, a more accurate assessment tool for MC-LR was obtained. This probe can specifically respond to MC-LR in aqueous solution, and its fluorescence signal is enhanced with the increase of MC-LR concentration. More importantly, the fluorescent signal of the probe showed a significant positive correlation with MC-LR concentration in water samples. This visualization tool has practical application potential for the preliminary assessment of MC-LR in eutrophic waters.

1α,25-dihydroxyvitamin D3 supplementation alleviates perfluorooctanesulfonate acid-induced reproductive injury in male mice: Modulation of Nrf2 mediated oxidative stress response.

Perfluorooctanesulfonate acid (PFOS) is a typical persistent organic pollutant that widely exists in the environment. To clarify the toxic effects and mechanisms of PFOS and to find effective intervention strategies have been attracted global attention. Here, we investigated the effects of PFOS on the male reproductive system and explored the potential protective role of 1α,25-dihydroxyvitamin D3 (1α,25(OH)2 D3 ). Our results showed that 1α,25(OH)2 D3 intervention significantly improved PFOS-induced sperm quality decline and testicular damage. Moreover, 1α,25(OH)2 D3 aggrandized the total antioxidant capacity. Furthermore, after PFOS exposure, the transcription factor nuclear factor erythroid-related factor 2 (Nrf2) was adaptively increased together with its target genes, such as HO-1, NQO1, and SOD2. Meanwhile, 1α,25(OH)2 D3 ameliorated PFOS-induced augment of Nrf2 and target genes. These findings indicated that 1α,25(OH)2 D3 might attenuate PFOS-induced reproductive injury in male mice via Nrf2-mediated oxidative stress.

N6-methyladenosine modifications of mRNAs and long noncoding RNAs in oxygen-induced retinopathy in mice.

Retinal neovascular diseases are major causes of blindness worldwide. As a common epitranscriptomic modification of eukaryotic RNAs, N6-methyladenosine (m6A) is associated with the pathogenesis of many diseases, including angiogenesis, through the regulation of RNA metabolism and functions. The aim of this study was to identify m6A modifications of mRNAs and long noncoding RNAs (lncRNAs) and determine their potential roles in retinal neovascularization. The transcriptome-wide m6A profiles of mRNAs and lncRNAs in the retinal tissues of mice with oxygen-induced retinopathy (OIR) and controls were identified by microarray analysis of immunoprecipitated methylated RNAs. The m6A methylation levels of mRNAs and lncRNAs identified in the microarray data were validated by MeRIP-qPCR. A total of 1321 mRNAs (151 hypermethylated and 1170 hypomethylated) and 192 lncRNAs (15 hypermethylated and 177 hypomethylated) were differentially methylated with the m6A modification in OIR and control mice. Gene ontology analysis showed that hypermethylated mRNAs were enriched in the regulation of multicellular organismal process, intracellular organelle, and protein binding, while hypomethylated mRNAs were enriched in cellular metabolic process, intracellular process, and binding. Kyoto Encyclopedia of Genes and Genomes pathway analysis indicated that hypermethylated mRNAs were involved in dopaminergic synapses, glutamatergic synapse, and PI3K-Akt signaling pathway, while hypomethylated mRNAs were involved in autophagy, ubiquitin-mediated proteolysis, and spliceosome. Moreover, the altered levels of m6A methylation of ANGPT2, GNG12, ROBO4, and ENSMUST00000153785 were validated by MeRIP-qPCR. The results revealed an altered m6A epitranscriptome in OIR retinas. These methylated RNAs may act as novel modulators and targets in retinal neovascularization.

Effect of 1α,25(OH)2D3-Treated M1 and M2 Macrophages on Cell Proliferation and Migration Ability in Ovarian Cancer.

The biological active form of vitamin D3, 1α,25-dehydroxyvitamin D3 [1α,25(OH)2D3], exerts pleiotropic effects including bone mineralization, anti-tumor, as well as immunomodulator. This study aimed to explore the potential impact of 1α,25(OH)2D3 on tumor-associated macrophages (TAMs) infiltration in ovarian cancer. Firstly, human monocytic THP-1 cells were differentiated into macrophages (M0) in the presence of phorbol 12-myristate 13-acetate (PMA). In Vivo, 1α,25(OH)2D3 not only reversed the polarization of M2 macrophages, but also decreased the proliferation and migration abilities of ovarian cancer cells induced by M2 macrophages supernatant. Furthermore, 1α,25(OH)2D3 dramatically decreased the secretion of TGF-ß1 and MMP-9 in M2 macrophages. However, no significant effect was observed in 1α,25(OH)2D3 treated M1 macrophages. In Vivo, vitamin D3 had an inhibitive effect of 1α,25(OH)2D3-treated M2 macrophages on tumorigenesis. In addition, we conducted the association of TAMs with the poor prognosis of patients with ovarian cancer by meta-analysis, which suggested the higher proportion of M2 macrophages was related to the poorer prognosis in ovarian cancer. Collectively, these results identified distinct roles of 1α,25(OH)2D3 treated M1 and M2 macrophages on cell proliferation and migration abilities in ovarian cancer.

Detection of Microcystin-LR in the Cells and Natural Lake Water Samples by A Unique Fluorescence-Based Method.

Microcystin-LR (MC-LR) is widely distributed in natural lakes and could strongly inhibit protein phosphatase activity; it is also a potent liver tumor promoter. Over the last two decades, tremendous efforts have been devoted to enhance the detection of MC-LR in water samples. However, the traditional method is complex and costly, and achieving the fast, sensitive, and accurate determination of MC-LR in the cells and natural lakes by using fluorescence signal changes is fairly difficult. Our work explores novel fluorescent probes that are capable of concurrently analyzing and detecting MC-LR in the cells and water. In this study, we introduce, for the first time, 5-AF and 6-AF as small-molecule fluorescent probes suitable for MC-LR detection in the cells and water samples based on fluorescence signal changes. We titrated 5-AF and 6-AF with MC-LR in pure water, scanned the fluorescence of the sample, and then obtained the equation the fluorescence intensity versus MC-LR concentration curve. MC-LR in lake water samples was crudely purified, and then 5-AF was added to measure its fluorescence peak. The fluorescence intensity of 5-AF is significantly enhanced with increasing MC-LR concentration. This enhancement trend is stable and could be mathematically modeled. We also comprehensively analyzed the mechanism and recognition principle of the probe response to MC-LR in natural lake water. Moreover, we believe that 5-AF may be capable of detecting exogenous MC-LR in cells. The results of this study reveal that these unique fluorescent probes may be applied to construct near-infrared fluorescent probes that could detect MC-LR levels in vivo.

Local climate adaptation and gene flow in the native range of two co-occurring fruit moths with contrasting invasiveness.

Invasive species pose increasing threats to global biodiversity and ecosystems. While previous studies have characterized successful invaders based on ecological traits, characteristics related to evolutionary processes have rarely been investigated. Here we compared gene flow and local adaptation using demographic analyses and outlier tests in two co-occurring moth pests across their common native range of China, one of which (the peach fruit moth, Carposina sasakii) has maintained its native distribution, while the other (the oriental fruit moth, Grapholita molesta) has expanded its range globally during the past century. We found that both species showed a pattern of genetic differentiation and an evolutionary history consistent with a common southwestern origin and northward expansion in their native range. However, for the noninvasive species, genetic differentiation was closely aligned with the environment, and there was a relatively low level of gene flow, whereas in the invasive species, genetic differentiation was associated with geography. Genome scans indicated stronger patterns of climate-associated loci in the noninvasive species. While strong local adaptation and reduced gene flow across its native range may have decreased the invasiveness of C. sasakii, this requires further validation with additional comparisons of invasive and noninvasive species across their native range.

Multi-omic dissection of the drought resistance traits of soybean landrace LX.

With diverse genetic backgrounds, soybean landraces are valuable resource for breeding programs. Herein, we apply multi-omic approaches to extensively characterize the molecular basis of drought tolerance in the soybean landrace LX. Initial screens established that LX performed better with PEG6000 treatment than control cultivars. LX germinated better than William 82 under drought conditions and accumulated more anthocyanin and flavonoids. Untargeted mass spectrometry in combination with transcriptomic analyses revealed the chemical diversity and genetic basis underlying the overall performance of LX landrace. Under control and drought conditions, significant differences in the expression of a suite of secondary metabolism genes, particularly those involved in the general phenylpropanoid pathway and flavonoid but not lignin biosynthesis, were seen in LX and William 82. The expression of these genes correlated with the corresponding metabolites in LX plants. Further correlation analysis between metabolites and transcripts identified pathway structural genes and transcription factors likely are responsible for the LX agronomic traits. The activities of some key biosynthetic genes or regulators were confirmed through heterologous expression in transgenic Arabidopsis and hairy root transformation in soybean. We propose a regulatory mechanism based on flavonoid secondary metabolism and adaptive traits of this landrace which could be of relevance to cultivated soybean.

Mechanical Insights into Thiol-Mediated Synergetic Biotransformation of Cadmium and Selenium in Nematodes.

Cadmium ion (Cd2+) is a common environmental pollutant with high biotoxicity. Interestingly, the Cd2+ biotoxicity can be alleviated by the coexisting selenite (SeO32-), which induces the formation of cadmium selenide-rich nanoparticles (CdSe NPs) under the function of thiol-capping peptides. However, the detailed biochemical mechanisms by which Cd and Se are synergistically transformed into CdSe NPs in living organisms remain unclear so far. Here, we shed light on the molecular basis of such biotransformation processes in Caenorhabditis elegans by focusing on the roles of several key thiol-capping peptides. By monitoring the compositional and structural changes of the Cd and Se species and the genetic-level responses of nematodes, we revealed the specific roles of glutathione (GSH) and phytochelatins (PCs) in mediating the CdSe NP formation. With the aid of in vitro bioassembly assay and density functional theory calculations, the detailed Cd-Se interaction pathways were further deciphered: the ingested Cd binds predominantly to GSH and PCs in sequence, then further interacts with selenocysteine to form tetrahedral-structured PC2-Cd2-Sec2 complex, and ultimately grows into CdSe NPs. This work provides molecular-level insights into the Cd-Se interaction in C. elegans and lays a basis for controlling the ecological and health risks of heavy metals in polluted environment.

Discovery of benzimidazole derivatives as potent and selective aldehyde dehydrogenase 1A1 (ALDH1A1) inhibitors with glucose consumption improving activity.

Aldehyde dehydrogenase 1A1 (ALDH1A1) plays vital physiological and toxicological functions in many areas, such as CNS, inflammation, metabolic disorders, and cancers. Overexpression of ALDH1A1 has been disclosed to play an important role in obesity, diabetes and other diseases, indicating the potential need for the identification and development of small molecule ALDH1A1 inhibitors. Herein, a series of benzimidazole derivatives was designed, synthesized and evaluated. Among them, compounds 21, 27, 29, 61 and 65 exhibited excellent inhibitory activity against ALDH1A1 with IC50 values in the low micromolar range and high selectivity over ALDH1A2, ALDH1A3, ALDH2 and ALDH3A1. Moreover, an in vitro study demonstrated that all five compounds effectively improved glucose consumption in HepG2 cells, of which, 61 and 65 at 10 µM produced nearly equal glucose consumption with positive control Metformin (Met) at 1 mM. Furthermore, 61 and 65 showed desirable metabolic stability in human liver microsomes. All these results suggest that 61 and 65 are suitable for further studies.

Geomagnetic Shielding Enhances Radiation Resistance by Promoting DNA Repair Process in Human Bronchial Epithelial Cells.

With the advent of long-duration space explorations, ionizing radiation (IR) may pose a constant threat to astronauts without the protection of Earth's magnetic field, or hypomagnetic field (HMF). However, the potential biological effects of a HMF on the cellular response to IR have not been well characterized so far. In this study, immortalized human bronchial epithelial cells were exposed to X-rays under either a geomagnetic field (GMF, ~50 uT) or HMF (<50 nT) culture condition. A significant increase of the cell survival rate in HMF after radiation was observed by colony formation analysis. The kinetics of DNA double-strand breaks (DSBs), determined by γH2AX foci formation and disappearance, presented a faster decrease of foci-positive cells and a significantly lower mean number of γH2AX foci per nucleus in HMF-cultured cells than in GMF-cultured cells after radiation. In addition, a γH2AX/53BP1 colocalization assay showed an upregulated DSB recovery rate in HMF cultured cells. These findings provided the first evidence that HMF exposure may enhance the cellular DSB repair efficiency upon radiation, and consequently modulate the genotoxic effects of IR.

1α,25(OH)2 D3 alleviates high glucose-induced lipid accumulation in rat renal tubular epithelial cells by inhibiting SREBPs.

Lipid accumulation is a vital event in the progression of diabetic nephropathy. 1,25-Dihydroxyvitamin D3 (1α,25(OH)2 D3 ) is considered to have a protective effect on diabetic nephropathy. However, it remains unclear whether 1α,25(OH)2 D3 can inhibit lipid accumulation, and the potential mechanisms responsible for lipid metabolism are incompletely understood. In this study, we evaluated the effects of 1α,25(OH)2 D3 on lipid metabolism in high glucose-exposed rat renal tubular epithelial NRK-52E cells. Results indicated that high glucose-enhanced lipid accumulation in NRK-52E cells and 1α,25(OH)2 D3 can remarkably decrease high glucose-induced lipid accumulation. Western blot showed that 1α,25(OH)2 D3 alleviated high glucose-induced upregulation of sterol regulatory element-binding protein-1c (SREBP-1c) and SREBP2, along with their established target genes fatty acid synthase (FASN) and hydroxymethylglutaryl CoA reductases (HMGCR). Overall, these findings suggest that 1α,25(OH)2 D3 downregulated the expressions of SREBPs to inhibit high glucose-induced lipid accumulation, which provides new sights into the protective effects of 1α,25(OH)2 D3 on diabetic nephropathy.