Genome-wide identification and functional analysis of the SiCIN gene family in foxtail millet (Setaria italica L.).

Cell wall invertase (CIN) is a vital member of plant invertase (INV) and plays a key role in the breakdown of sucrose. This enzyme facilitates the hydrolysis of sucrose into glucose and fructose, which is crucial for various aspects of plant growth and development. However, the function of CIN genes in foxtail millet (Setaria italica) is less studied. In this research, we used the blast-p of NCBI and TBtools for bidirectional comparison, and a total of 13 CIN genes (named SiCINs) were identified from foxtail millet by using Arabidopsis and rice CIN sequences as reference sequences. The phylogenetic tree analysis revealed that the CIN genes can be categorized into three subfamilies: group 1, group 2, and group 3. Furthermore, upon conducting chromosomal localization analysis, it was observed that the 13 SiCINs were distributed unevenly across five chromosomes. Cis-acting elements of SiCIN genes can be classified into three categories: plant growth and development, stress response, and hormone response. The largest number of cis-acting elements were those related to light response (G-box) and the cis-acting elements related to seed-specific regulation (RY-element). qRT-PCR analysis further confirmed that the expression of SiCIN7 and SiCIN8 in the grain was higher than that in any other tissues. The overexpression of SiCIN7 in Arabidopsis improved the grain size and thousand-grain weight, suggesting that SiCIN7 could positively regulate grain development. Our findings will help to further understand the grain-filling mechanism of SiCIN and elucidate the biological mechanism underlying the grain development of SiCIN.

Association between body mass index and medication-overuse headache among individuals with migraine: a cross-sectional study.

INTRODUCTION: Medication-overuse headache (MOH) is a secondary chronic headache disorder that occurs in individuals with a pre-existing primary headache disorder, particularly migraine disorder. Obesity is often combined with chronic daily headaches and is considered a risk factor for the transformation of episodic headaches into chronic headaches. However, the association between obesity and MOH among individuals with migraine has rarely been studied. The present study explored the association between body mass index (BMI) and MOH in people living with migraine. METHODS: This cross-sectional study is a secondary analysis of data from the Survey of Fibromyalgia Comorbidity with Headache study. Migraine and MOH were diagnosed using the criteria of the International Classification of Headache Disorders, 3rd edition. BMI (kg/m2) is calculated by dividing the weight (kg) by the square of the height (m). Multivariable logistic regression analysis was used to evaluate the association between BMI and MOH. RESULTS: A total of 2,251 individuals with migraine were included, of whom 8.7% (195/2,251) had a concomitant MOH. Multivariable logistic regression analysis, adjusted for age, sex, education level, headache duration, pain intensity, headache family history, chronic migraine, depression, anxiety, insomnia, and fibromyalgia, demonstrated there was an association between BMI (odds ratio [OR], 1.05; 95% confidence interval [CI], 1.01-1.11; P = 0.031) and MOH. The results remained when the BMI was transformed into a category. Compared to individuals with Q2 (18.5 kg/m2 ≤ BMI ≤ 23.9 kg/m2), those with Q4 (BMI ≥ 28 kg/m2) had an adjusted OR for MOH of 1.81 (95% CI, 1.04-3.17; P = 0.037). In the subgroup analyses, BMI was associated with MOH among aged more than 50 years (OR, 1.13; 95%, 1.03-1.24), less than high school (OR, 1.08; 95%, 1.01-1.15), without depression (OR, 1.06; 95%, 1.01-1.12), and without anxiety (OR, 1.06; 95%, 1.01-1.12). An association between BMI and MOH was found in a sensitivity analysis that BMI was classified into four categories according to the World Health Organization guidelines. CONCLUSION: In this cross-sectional study, BMI was associated with MOH in Chinese individuals with migraine.

Exosome-Derived MicroRNA-221-3p Desensitizes Breast Cancer Cells to Adriamycin by Regulating PIK3r1-Mediated Glycose Metabolism.

Background: Cancer-derived exosomes facilitate chemoresistance by transferring RNAs, yet their role in exosomal microRNA-221-3p (miR-221-3p) regulation of Adriamycin resistance in breast cancer (BC) remains unclear. Methods: Adriamycin-resistant BC cells were developed from MCF-7 and MDA-MB-231 cells by incremental Adriamycin exposure. The miR-221-3p levels were quantified by quantitative reverse transcription-polymerase chain reaction. Subsequently, exosomes were isolated and incubated with BC cells, and exosome-mediated Adriamycin sensitivity was evaluated using Cell Counting Kit-8, colony formation, and flow cytometry assays. Sensitive cells were cocultured with miR-221-3p inhibitor-treated cells to assess Adriamycin resistance. Moreover, the interaction between miR-221-3p and phosphoinositide-3-kinase regulatory subunit 1 (PIK3R1) was validated using a dual luciferase reporter gene assay. Mimics and inhibitors were used to determine the effects of miR-221-3p on Adriamycin resistance. Results: Elevated levels of miR-221-3p expression were observed in Adriamycin-resistant BC cells and exosomes. Sensitive cells were cocultured with exosomes from resistant cells, resulting in increased half-maximal inhibitory concentration value and proliferation, and reduced Adriamycin-induced apoptosis. However, the effects of coculturing sensitive cells with Adriamycin-resistant cells were significantly weakened by miR-221-3p inhibitor transfection in Adriamycin-resistant cells. PIK3R1 was found to be a target of miR-221-3p, and miR-221-3p mimics enhanced Adriamycin resistance in sensitive cells. miR-221-3p inhibitors increased the expression of PIK3R1, p-AKT, c-Myc, HK2, and PKM2, decreased FOXO3 expression, and weakened the Adriamycin resistance in resistant cells. Conclusions: miR-221-3p can be transferred between BC cells through exosomes. High levels of miR-221-3p were found to target PIK3R1 and promoted Adriamycin resistance in BC cells. [Figure: see text].

The Added Value of ADC-based Nomogram in Assessing the Depth of Myometrial Invasion of Endometrial Endometrioid Adenocarcinoma.

RATIONALE AND OBJECTIVES: To explore the potential value of the apparent diffusion coefficient (ADC)-based nomogram models in preoperatively assessing the depth of myometrial invasion of endometrial endometrioid adenocarcinoma (EEA). MATERIALS AND METHODS: Preoperative magnetic resonance imaging (MRI) of 210 EEA patients were retrospectively analyzed. ADC histogram metrics derive from the whole-tumor regions of interest. Univariate and multivariate analyses were used to screen the ADC histogram metrics and clinical characteristics for nomogram model building. The diagnostic sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV) of two radiologists without and with the assistance of models were calculated and compared. RESULTS: Two nomogram models were developed for predicting no myometrial invasion (NMI) and deep myometrial invasion (DMI) with area under the curves of 0.85 and 0.82, respectively. With the assistance of models, the overall accuracies were significantly improved [radiologist_1, 73.3% vs 86.2% (p = 0.001); radiologist_2, 80.0% vs 91.0% (p = 0.002)]. In determining NMI, the sensitivity and PPV were greatly improved but not significant for radiologist_1 (51.9% vs 77.8% and 46.7% vs 75.0%, p = 0.229 and 0.511), and under/near the significance level for radiologist_2 (59.3% vs 88.9% and 57.1% vs 82.8%, p = 0.041 and 0.065), while the specificity, accuracy, and NPV were significantly improved (all p < 0.001). In determining DMI, all sensitivity, specificity, accuracy, PPV, and NPV were significantly improved (all p < 0.001). CONCLUSION: The ADC-based nomogram models can improve the diagnostic performance of radiologist in preoperatively assessing the depth of myometrial invasion and facilitate optimizing clinical individualized treatment decisions.

Physcion increases the sensitivity of hepatocellular carcinoma to sorafenib through miRNA-370/PIM1 axis-regulated glycolysis.

BACKGROUND: Resistance to sorafenib has become a challenge in clinical treatment of hepatocellular carcinoma (HCC). Physcion is a common bioactive anthraquinone that has potential as an anticancer agent. AIM: To study the effect of physcion on sensitizing HCC cells to sorafenib. METHODS: Sorafenib-resistant HCC cells were established and treated with sorafenib and/or physcion. The cell viability, proliferation and apoptosis were measured by cell counting kit-8, colony formation, flow cytometry, and in vivo xenograft model. Glucose uptake, lactate acid production, extracellular acidification rate (ECAR), and oxygen consumption rate (OCR) were measured to analyze glycolysis. Expression of glycolysis-related regulators was assessed by western blotting. RESULTS: The addition of physcion significantly enhanced the antitumor effects of sorafenib on sorafenib-resistant HCC cells, manifested by enhanced apoptosis and suppressed cell growth. The glucose uptake, lactate acid production, and ECAR were elevated, and OCR was suppressed by physcion treatment. The level of PIM1 was elevated and miR-370 was suppressed in sorafenib-resistant HCC cells compared with the parental cells, which was suppressed by physcion treatment. Inhibition of miR-370 notably reversed the effects of physcion on sorafenib-resistant HCC cells. CONCLUSION: Our data indicated that physcion enhanced the sensitivity of HCC cells to sorafenib by enhancing miR-370 to suppress PIM1-promoted glycolysis.

Status of diagnosis and preventative treatment for primary headache disorders: real-world data of unmet needs in China.

BACKGROUND: Headache disorders are widely prevalent and pose a considerable economic burden on individuals and society. Globally, misdiagnosis and inadequate treatment of primary headache disorders remain significant challenges, impeding the effective management of such conditions. Despite advancements in headache management over the last decade, a need for comprehensive evaluations of the status of primary headache disorders in China regarding diagnosis and preventative treatments persists. METHODS: In the present study, we analyzed the established queries in the Survey of Fibromyalgia Comorbidity with Headache (SEARCH), focusing on previous diagnoses and preventative treatment regimens for primary headache disorders. This cross-sectional study encompassed adults diagnosed with primary headache disorders who sought treatment at 23 hospitals across China between September 2020 to May 2021. RESULTS: The study comprised 2,868 participants who were systematically examined. Migraine and tension-type headaches (TTH) constituted a majority of the primary headache disorders, accounting for 74.1% (2,124/2,868) and 23.3% (668/2,868) of the participants, respectively. Medication overuse headache (MOH) affected 8.1% (231/2,868) of individuals with primary headache disorders. Over half of the individuals with primary headache disorders (56.6%, 1,624/2,868) remained undiagnosed. The previously correct diagnosis rates for migraine, TTH, TACs, and MOH were 27.3% (580/2,124), 8.1% (54/668), 23.2% (13/56), and 3.5% (8/231), respectively. The misdiagnosis of "Nervous headache" was found to be the most prevalent among individuals with migraine (9.9%, 211/2,124), TTH (10.0%, 67/668), trigeminal autonomic cephalalgias (TACs) (17.9%, 10/56), and other primary headache disorders (10.0%, 2/20) respectively. Only a minor proportion of individuals with migraine (16.5%, 77/468) and TTH (4.7%, 2/43) had received preventive medication before participating in the study. CONCLUSIONS: While there has been progress made in the rate of correct diagnosis of primary headache disorders in China compared to a decade ago, the prevalence of misdiagnosis and inadequate treatment of primary headaches remains a veritable issue. As such, focused efforts are essential to augment the diagnosis and preventive treatment measures related to primary headache disorders in the future.

The prevalence and clinical features of fibromyalgia in Chinese hospital patients with primary headache: The survey of fibromyalgia comorbid with headache.

OBJECTIVE: The aims were to explore the prevalence and clinical features of fibromyalgia in Chinese hospital patients with primary headache. BACKGROUND: Studies done in non-Chinese populations suggest that around one-third of patients with primary headache have fibromyalgia, but data from mainland China are limited. Investigations into the prevalence and clinical features of fibromyalgia in Chinese patients with primary headache would improve our understanding of these two complex disease areas and help guide future clinical practice. METHODS: This cross-sectional study included adults with primary headache treated at 23 Chinese hospitals from September 2020 to May 2021. Fibromyalgia was diagnosed using the modified 2010 American College of Rheumatology criteria. Mood and insomnia were evaluated employing the Hospital Anxiety and Depression Scale and the Insomnia Severity Index. RESULTS: A total of 2782 participants were analyzed. The fibromyalgia prevalence was 6.0% (166/2782; 95% confidence interval: 5.1%, 6.8%). Compared to primary headache patients without combined fibromyalgia, patients with primary headache combined with fibromyalgia were more likely to be older (47.8 vs. 41.7 years), women (83.7% [139/166] vs. 72.8% [1904/2616]), less educated (65.1% [108/166] vs. 45.2% [1183/2616]), and with longer-duration headache (10.0 vs. 8.0 years). Such patients were more likely to exhibit comorbid depression (34.3% [57/166] vs. 9.9% [260/2616]), anxiety (16.3% [27/166] vs. 2.7% [70/2612]), and insomnia (58.4% [97/166] vs. 17.1% [447/2616]). Fibromyalgia was more prevalent in those with chronic (rather than episodic) migraine (11.1% [46/414] vs. 4.4% [72/1653], p < 0.001) and chronic (rather than episodic) tension-type headache (11.5% [27/235] vs. 4.6% [19/409], p = 0.001). Most fibromyalgia pain was in the shoulders, neck, and upper back. CONCLUSIONS: The prevalence of fibromyalgia in mainland Chinese patients with primary headache was 6.0%. Fibromyalgia was more common in those with chronic rather than episodic headache. The most common sites of fibromyalgia pain were the neck, shoulders, and back.

Genome-wide chromatin accessibility analysis unveils open chromatin convergent evolution during polyploidization in cotton.

Allopolyploidization, resulting in divergent genomes in the same cell, is believed to trigger a "genome shock", leading to broad genetic and epigenetic changes. However, little is understood about chromatin and gene-expression dynamics as underlying driving forces during allopolyploidization. Here, we examined the genome-wide DNase I-hypersensitive site (DHS) and its variations in domesticated allotetraploid cotton (Gossypium hirsutum and Gossypium barbadense, AADD) and its extant AA (Gossypium arboreum) and DD (Gossypium raimondii) progenitors. We observed distinct DHS distributions between G. arboreum and G. raimondii. In contrast, the DHSs of the two subgenomes of G. hirsutum and G. barbadense showed a convergent distribution. This convergent distribution of DHS was also present in the wild allotetraploids Gossypium darwinii and G. hirsutum var. yucatanense, but absent from a resynthesized hybrid of G. arboreum and G. raimondii, suggesting that it may be a common feature in polyploids, and not a consequence of domestication after polyploidization. We revealed that putative cis-regulatory elements (CREs) derived from polyploidization-related DHSs were dominated by several families, including Dof, ERF48, and BPC1. Strikingly, 56.6% of polyploidization-related DHSs were derived from transposable elements (TEs). Moreover, we observed positive correlations between DHS accessibility and the histone marks H3K4me3, H3K27me3, H3K36me3, H3K27ac, and H3K9ac, indicating that coordinated interplay among histone modifications, TEs, and CREs drives the DHS landscape dynamics under polyploidization. Collectively, these findings advance our understanding of the regulatory architecture in plants and underscore the complexity of regulome evolution during polyploidization.

Exosomes from HPV-16 E7-pulsed dendritic cells prevent the migration, M1 polarization, and inflammation of macrophages in cervical cancer by regulating catalase 2 (CAT2).

Background: Cervical cancer is mainly caused by persistent infection with human papillomavirus (HPV), especially HPV-16. Recently, HPV-16 E7-modified dendritic cells (DCs) have been reported to play a blocking role in the progression of cervical cancer. Conversely, the effect and mechanism of HPV-16 E7-pulsed DCs in cervical cancer are not entirely clear. Methods: DCs from the peripheral blood of patients with cervical cancer were induced with lipopolysaccharide and identified through the detection of cluster of differentiation (CD)11c, major histocompatibility complex (MHC)-II, CD83, and CD40 levels, and exosomes from HPV-16 E7-pulsed and catalase 2 (CAT2)-silenced DCs were extracted and identified through transmission electron microscopy and the detection of markers. Additionally, the migration, inflammatory factors, and polarization of macrophages were confirmed using Transwell, enzyme-linked immunoassay, and Western blot of arginase-1 (Arg-1) and inducible nitric oxide synthase (iNOS). In vivo, we also built a mice xenograft model of HPV cervical cancer. Results: We first successfully induced and identified DCs from cervical cancer patients, and successfully extracted and confirmed the exosomes from the constructed HPV-16 E7-pulsed and CAT2-silenced DCs. Subsequently, we proved that exosomes from HPV-16 E7-pulsed DCs restrained migration and inflammation and induced M2 polarization in macrophages, while the effect of exosomes from CAT2-silenced DCs on macrophage migration, polarization, and inflammation was opposite to that of exosomes from HPV-16 E7-pulsed DCs, and the 2 affected each other. Additionally, we found that exosomes from CAT2-silenced DCs also prevented growth and M2 polarization in a mice xenograft model of HPV cervical cancer. Conclusions: Exosomes from HPV-16 E7-pulsed DCs blocked cervical cancer progression by regulating macrophage function, and its mechanism was relevant to CAT2.

Effect of m6A methyltransferase METTL3 -mediated MALAT1/E2F1/AGR2 axis on adriamycin resistance in breast cancer.

N6-methyladenosine (m6A) methyltransferase METTL3 has been implicated in carcinogenesis, which may be associated the overexpression of MALAT1. However, the downstream mechanics actions remain largely unknown. This study intends to probe the downstream mechanism of the N6-methyladenosine (m6 A) methyltransferase METTL3 and MALAT1 in adriamycin resistance in breast cancer. Through Bioinformatics databases lncMAP, TCGA and GTEx, we predicted the downstream transcription factors E2F1 and AGR2 of MALAT1 in breast cancer. The Cancer Genome Atlas and Genotype-Tissue Expression (GTEx) databases were used to screen the downstream target genes of MALAT1. MeRIP-qPCR was used to detect the m6 A level of MALAT1 in cells. RIP was used to detect the binding between MALAT1 and E2F1, and chromatin immunoprecipitation (ChIP) for the binding of E2F1 to AGR2 promoter. Cell Counting Kit-8 and colony formation assays were used to detect cell viability. Transwell was used to detect cell invasion. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) and western blot were used to detect the expression of related genes and proteins. A nude mouse xenograft tumor model was established to observe the effect of METTL3 on adriamycin resistance of breast cancer. The total survival of mice after exogenous gene silencing was analyzed by the Kaplan-Meier method. METTL3 was highly expressed in adriamycin-resistant breast cancer cells. METTL3 promotes adriamycin resistance in breast cancer cells. METTL3 mediates the expression of MALAT1 in adriamycin-resistant breast cancer through m6 A. MALAT1 increases adriamycin resistance in breast cancer cells by recruiting E2F1 to activate AGR2 transcription. METTL3 can regulate the expression of MALAT1 through m6 A, mediate the E2F1/AGR2 axis, and promote the adriamycin resistance of breast cancer. METTL3 may modify MALAT1 protein through m6 A, recruit E2F1 and activate downstream AGR2 expression, thus promoting adriamycin resistance in breast cancer.

Detection of Caenorhabditis elegans Germ Cell Apoptosis Following Exposure to Environmental Contaminant Mixtures: A Crude Oil-Dispersant Mixture Example.

Crude oil disasters, such as the Deepwater Horizon accident, have caused severe environmental contamination and damage, affecting the health of marine and terrestrial organisms. Some previous studies have demonstrated cleanup efforts using chemical dispersant induced more potent toxicities than oil alone due to an increase in bioavailability of crude oil components, such as PAHs. However, there still lacks a systematic procedure that provides methods to determine genotypic and phenotypic changes following exposure to environmental toxicants or toxicant mixture, such as dispersed crude oil. Here, we describe methods for identifying a mechanism of dispersed crude oil-induced reproductive toxicity in the model organisms, Caenorhabditis elegans (C. elegans). Due to the genetic malleability of C. elegans, two mutant strains outlined in this chapter were used to identify a pathway responsible for inducing apoptosis: MD701 bcIs39 [lim-7p::ced-1::GFP + lin-15(+)], a mutant strain that allows visualization of apoptotic bodies via a green fluorescent protein fused to CED-1; and TJ1 (cep-1(gk138) I.), a p53/CEP-1 defective strain that is unable to activate apoptosis via the p53/CEP-1 pathway. In addition, qRT-PCR was utilized to demonstrate the aberrant expression of apoptosis (ced-13, ced-3, ced-4, ced-9, cep-1, dpl-1, efl-1, efl-2, egl-1, egl-38, lin-35, pax-2, and sir-2.1) and cytochrome P450 (cyp14a3, cyp35a1, cyp35a2, cyp35a5, and cyp35c1) protein-coding genes following exposure to dispersed crude oil. The procedure outlined here can be applicable to determine whether environmental contaminants, most of time contaminant mixture, cause reproductive toxicity by activation of the proapoptotic, p53/CEP-1 pathway.

Identification of Stable Reference Genes for Toxicogenomic and Gene Expression Analysis.

Gene expression analysis has been becoming a popular method for studying gene function and response to different environmental stresses, including toxin/pollution exposure. Selection of a suitable reference gene is critically important for gene expression analysis due to that wrong reference genes will cause misleading and even wrong conclusion. A good reference gene should be a more stable reference gene, particularly during the toxicant exposure treatment and/or other investigation condition. In this chapter, a step-by-step protocol is present for primer design, reverse transcription PCR, primer efficiency and specificity test, qRT-PCR, and the strategy for identifying most stable reference genes for toxicogenomic and gene expression analysis. The detailed method for determining the primer gene specificity and primer efficiency are also presented in this chapter. Low primer efficiency will affect the fold changes during gene expression analysis; however, it does not affect the conclusion, up- or downregulation. Choosing a wrong reference gene may result in wrong conclusion.

Determination of the N-Nitroso Compounds in Mouse Following RDX Exposure.

Hexahydro-1,3,5-trinitro-1,3,5-triazine, commonly called RDX, is an important explosive, which is widely used in military and civic activities. As it is used, RDX is widely found in many locations and caused soil and water contamination. Many studies show that RDX is toxic to many organisms, including plants, animals, and microbes. RDX causes genetic toxicity and neurotoxicity as well as potential carcinogenesis. Even it is worse that RDX can be biotransformed into other N-nitroso derivatives, such as MNX, DNX, and TNX; these derivatives can be found in both naturally in RDX-contaminated soil and also in the animal GI tracks. To study the potential effect of RDX and its N-nitroso derivatives, this chapter presents a step-by-step method for detect RDX and its N-nitroso derivatives in animal stomach and GI tracts followed RDX exposure by gas chromatography with electron capture detector (GC/ECD). This method can also be used to detect RDX and its N-nitroso derivatives in other tissues and in other animals and plants.

METTL3 promotes adriamycin resistance in MCF-7 breast cancer cells by accelerating pri-microRNA-221-3p maturation in a m6A-dependent manner.

Breast cancer (BC) is the most prevalent malignant neoplasm among women and is the fifth most common cause of cancer-associated death worldwide. Acquired chemoresistance driven by genetic and epigenetic alterations is a significant clinical challenge in treating BC. However, the mechanism of BC cell resistance to adriamycin (ADR) remains to be elucidated. In this study, we identified the methyltransferase-like 3/microRNA-221-3p/homeodomain-interacting protein kinase 2/Che-1 (METTL3/miR-221-3p/HIPK2/Che-1) axis as a novel signaling event that may be responsible for resistance of BC cells to ADR. A dual-luciferase reporter gene assay was employed to test the presence of miR-221-3p binding sites in the 3'UTR of HIPK2. Drug resistance was evaluated by immunoblotting multidrug resistance protein 1 (MDR1) and breast cancer resistance protein (BCRP). Cultured ADR-resistant MCF-7 cells were assayed for their half maximal inhibitory concentration (IC50) values and apoptosis using an MTT assay and Annexin V-FITC/PI-labeled flow cytometry, and the cells were then xenografted into nude mice. METTL3 knockdown was shown to reduce the expression of miR-221-3p by reducing pri-miR-221-3p m6A mRNA methylation, thereby reducing the IC50 value of ADR-resistant MCF-7 cells, reducing the expression of MDR1 and BCRP, and inducing apoptosis. Mechanistically, miR-221-3p was demonstrated to negatively regulate HIPK2 and upregulate its direct target Che-1, thus leading to enhanced drug resistance in ADR-resistant MCF-7 cells. In vitro results were reproduced in nude mice xenografted with ADR-resistant MCF-7 cells. Our work elucidates an epigenetic mechanism of acquired chemoresistance in BC, in support of the METTL3/miR-221-3p/HIPK2/Che-1 axis as a therapeutic target for the improvement of chemotherapy.

Quantitative analysis of PAH compounds in DWH crude oil and their effects on Caenorhabditis elegans germ cell apoptosis, associated with CYP450s upregulation.

The Deepwater Horizon (DWH) oil spill marked the largest environmental oil spill in human history, where it was estimated a large amount of the polycyclic aromatic hydrocarbons (PAHs) were released with crude oil into the environment. In this study, common PAH compounds were quantitatively determined in crude oil from the DWH spill by gas chromatography-mass spectroscopy (GC-MS). Twelve PAH compounds were identified and quantified from a 100× dilution of DWH crude oil: naphthalene (7800 ng/mL), acenaphthylene (590 ng/mL), acenaphtehen (540 ng/mL), fluorene (2550 ng/mL), phenanthrene (2910 ng/mL), anthracene (840 ng/mL), fluoranthene (490 ng/mL), pyrene (290 ng/mL), benzo(k) fluoranthene (1050 ng/mL), benzo(b)fluoranthene (1360 ng/mL), dibenz(a,h)anthracene (2560 ng/mL), and benzo(g, h, i) perylene (630 ng/mL). Toxicity assays using the nematode, Caenorhabditis elegans (C. elegans), indicated a single PAH compound naphthalene, exposure increased C. elegans germ cell apoptosis which may adversely affect progeny reproduction. The number of apoptotic germ cells significantly increased from 1.4 to 2.5 when worms were treated with 10 µg/mL of naphthalene and from 1.3 to 2.5 and 3.5 cells in presence of 1 µg/mL and 5 µg/mL of benzo(a)pyrene, respectively. Five CYP450 genes (CYP14A3, CYP35A1, CYP35A2, CYP35A5, and CYP35C1) were significantly upregulated following 500× dilution of dispersed crude oil exposure (p < 0.05). These results suggest that CYP450s may play a role in bioactivation of PAHs in crude oil, resulting in DNA damage related germ cell apoptosis.

Exosomal MicroRNA-221-3p Confers Adriamycin Resistance in Breast Cancer Cells by Targeting PIK3R1.

Drug resistance in breast cancer (BC) cells continues to be a stern obstacle hindering BC treatment. Adriamycin (ADR) is a frequently employed chemotherapy agent used to treat BC. The exosomal transfer of microRNAs (miRNAs) has been reported to enhance the drug-resistance of BC cells. Herein, we first sought to elucidate the possible role of the exosomal transfer of miR-221-3p in the drug resistance of MCF-7 cells to ADR. Differentially expressed genes (DEGs) were initially screened through microarray analysis in BC drug resistance-related datasets. Next, the expression of miR-221-3p and phosphoinositide-3-kinase regulatory subunit 1 (PIK3R1) was quantified in ADR-resistant MCF-7 (MCF-7/ADR) and ADR-sensitive MCF-7 (MCF-7/S) cell lines, after which exosomes were separated and identified in each cell line. Target relationship between miR-221-3p and PIK3R1 was validated by a dual-luciferase reporter assay. Next, the expression of miR-221-3p and PIK3R1 was altered to clarify their effects on the resistance of MCF-7 cells to ADR in vitro and in vivo. PIK3R1 was identified as a BC drug resistance-related DEG, with the regulatory miR-221-3p subsequently obtained. Moreover, the MCF-7/ADR cells exhibited a low expression of PIK3R1 and a high expression of miR-221-3p. Notably, PIK3R1 was identified as a target gene of miR-221-3p. The overexpression of miR-221-3p in MCF-7/ADR cell-derived exosomes promoted ADR resistance in MCF-7/S cells via the PI3K/AKT signaling pathway. The in vitro results were reproducible in in vivo assays. Taken together, drug-resistant BC cell-derived exosomal miR-221-3p can promote the resistance of BC cells to ADR by targeting PIK3R1 via the PI3K/AKT signaling pathway in vitro and in vivo. These findings provide encouraging insights and provide perspectives for further investigation into the BC drug resistance mechanism.

Adipose-tissue derived porcine mesenchymal stem cells efficiently ameliorate CCl4-induced acute liver failure in mice.

Adipose tissue derived mesenchymal stem cells (ADMSCs) may be an attractive therapeutic source for acute liver injury because of their high accessibility and non-invasiveness. Here, we investigated the therapeutic potentials of porcine ADMSCs for acute liver failure (ALF). The morphology, differentiation potential, expression patterns of cell surface markers and liver-specific genes were compared between the ADMSCs derived from the pigs with or without ALF. For therapeutic studies, the expanded porcine ADMSCs from either ALF pig (ALF-ADMSCs) or healthy control pig (Nor-ADMSCs) of passage 3 were transplanted into CCl4-induced ALF mice, and the liver histology and functional tests were performed at days 1, 7, 14, and 21 after cell transplantation. ALF-ADMSCs expressed higher mRNA level of hepatic growth factor (HGF) than the Nor-ADMSCs. Both ALF-ADMSCs and Nor-ADMSCs improved liver histology, functions, and mouse survival rate. Higher level of porcine hepatocyte-specific genes was seen in the livers of ALF-ADMSCs transplanted mice as compared to the Nor-ADMSCs transplanted mice. In particular, ALF-ADMSCs transplanted mice expressed significantly higher level of albumin and cytokeratin 18 in the liver tissues as compared to the Nor-ADMSCs transplanted mice. ALF-ADMSCs might be superior to Nor-ADMSCs in the treatment of ALF as the former possesses stronger hepatic differentiation potential.

Physcion Synergistically Enhances the Cytotoxicity of Sorafenib in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is a common human malignancy. Physcion is a naturally occurring anthraquinone derivative found in plant and marine sources. Our previous studies have indicated that physcion could suppress tumor growth and induce apoptosis in HCC. This study was aimed to investigate the effect of a combination of physcion and sorafenib on HCC. Our findings indicated that physcion could significantly augment the antiproliferative and proapoptotic activities of sorafenib in vitro and in vivo. Mechanistically, the synergistic effect correlates with physcion-induced suppression of Notch3/AKT signaling. This preclinical evidence highlights the potential application of physcion in the treatment of HCC. Anat Rec, 302:2171-2177, 2019. © 2019 American Association for Anatomy.

RETRACTED: Protective autophagy induced by physcion suppresses hepatocellular carcinoma cell metastasis by inactivating the JAK2/STAT3 Axis.

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). This article has been retracted at the request of the Editor-in-Chief and the authors, as panels from Figure 6F appear as similar to panels from Figure 2B of the article published by Ming-Quan Gao, Hui Gao, Mei Han, Kai-Li Liu, Jian-Jun Peng and Yan-Tao Han in the American Journal of Cancer Research 7 (2017) 1501­1514 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5523031/ and Figures 2E and 3E of the article published by Meizhi Wang, Hui Gao, Haijun Qu, Jing Li, Kaili Liu and Zhiwu Han in Pharmacological Reports 70 (2018) 963­971 https://doi.org/10.1016/j.pharep.2018.04.006. Also, the Vehicle panel from Figure 7E appears as similar to the Vehicle panel from Figure 3D of the article published by Bo Liu and Shuo Yu in Biomedicine & Pharmacotherapy 107 (2018) 243­253 https://doi.org/10.1016/j.biopha.2018.07.177. Figure 7E appears also as similar to Figure 6(b) of the article published by Mei Han, Hui Gao, Jing Xie, Yin-ping Yuan, Quan Yuan, Ming-quan Gao, Kai-li Liu, Xue-hong Chen, Yan-tao Han and Zhi-wu Han in Acta Pharmacologica Sinica volume 40 (2019) 666­676 https://doi.org/10.1038/s41401-018-0159-7. Moreover, panels from Figure 7F appear as similar to panels from Figure 7E of the Reference [1], Figure 6D of the Reference [2], Figure 6C of the Reference [3], Figure 8C of the Reference [4], Figure 8D of the Reference [5] and Figure 6B of the Reference [6]. One of the conditions of submission of a paper for publication is that authors declare explicitly that their work is original and has not appeared in a publication elsewhere. Re-use of any data should be appropriately cited. As such this article represents a severe abuse of the scientific publishing system. The scientific community takes a very strong view on this matter and apologies are offered to readers of the journal that this was not detected during the submission process.