Causal relationship between female reproductive factors, sex hormones and uterine leiomyoma: a Mendelian randomization study.

RESEARCH QUESTION: Are the observed associations between female reproductive factors and sex hormones with the risk of uterine leiomyoma truly causal associations? DESIGN: The putative causal relationships between female reproductive factors and sex hormones with uterine leiomyoma were investigated using two-sample Mendelian randomization. Statistics on exposure-associated genetic variants were obtained from genome-wide association studies (GWAS). The uterine leiomyoma GWAS from the FinnGen and FibroGENE consortia were used as outcome data for discovery and replication analyses, respectively. Results were pooled by meta-analysis. Sensitivity analyses ensured robustness of the Mendelian randomization analysis. RESULTS: When FinnGen GWAS were used as outcome data, a causal relationship was found between age at menarche (OR 0.84, P < 0.0001), age at menopause (OR 1.08, P < 0.0001), number of live births (OR 0.25, P < 0.001) and total testosterone levels (OR 0.90, P < 0.001) with the risk of uterine leiomyoma. When FibroGENE GWAS were used as outcome data, Mendelian randomization results for age at menopause, the number of live births and total testosterone levels were replicated. In the meta-analysis, a later age at menopause (OR 1.08, P < 0.0001) was associated with an increased risk of uterine leiomyoma. A higher number of live births (OR 0.25, P < 0.0001) and higher total testosterone levels (OR 0.90, P < 0.0001) were associated with a decreased risk of uterine leiomyoma. CONCLUSIONS: A causal relationship between later age at menopause, lower number of live births and lower total testosterone levels with increased risk of uterine leiomyoma was found.

Remediation of arsenic- and nitrate-contaminated groundwater through iron-dependent autotrophic denitrifying culture.

Groundwater contamination with arsenic and nitrate poses a pressing concern for the safety of local communities. Bioremediation, utilizing Fe(II)-oxidizing nitrate reducing bacteria, shows promise as a solution to this problem. However, the relatively weak environmental adaptability of a single bacterium hampers practical application. Therefore, this study explored the feasibility and characteristics of a mixed iron-dependent autotrophic denitrifying (IDAD) culture for effectively removing arsenic and nitrate from synthetic groundwater. The IDAD biosystem exhibited stable performace and arsenic resistance, even at a high As(III) concentration of 800 µg/L. Although the nitrogen removal efficiency of the IDAD biosystem decreased from 71.4% to 64.7% in this case, the arsenic concentration in the effluent remained below the standard (10 µg/L) set by WHO. The crystallinity of the lepidocrocite produced by the IDAD culture decreased with increasing arsenic concentration, but the relative abundance of the key iron-oxidizing bacteria norank_f_Gallionellaceae in the culture showed an opposite trend. Metagenomic analysis revealed that the IDAD culture possess arsenic detoxification pathways, including redox, methylation, and efflux of arsenic, which enable it to mitigate the adverse impact of arsenic stress. This study provides theoretical understanding and technical support for the remediation of arsenic and nitrate-contaminated groundwater using the IDAD culture.

Activation of HCA2 regulates microglial responses to alleviate neurodegeneration in LPS-induced in vivo and in vitro models.

BACKGROUND: Previous studies have shown a close association between an altered immune system and Parkinson's disease (PD). Neuroinflammation inhibition may be an effective measure to prevent PD. Recently, numerous reports have highlighted the potential of hydroxy-carboxylic acid receptor 2 (HCA2) in inflammation-related diseases. Notably, the role of HCA2 in neurodegenerative diseases is also becoming more widely known. However, its role and exact mechanism in PD remain to be investigated. Nicotinic acid (NA) is one of the crucial ligands of HCA2, activating it. Based on such findings, this study aimed to examine the effect of HCA2 on neuroinflammation and the role of NA-activated HCA2 in PD and its underlying mechanisms. METHODS: For in vivo studies, 10-week-old male C57BL/6 and HCA2-/- mice were injected with LPS in the substantia nigra (SN) to construct a PD model. The motor behavior of mice was detected using open field, pole-climbing and rotor experiment. The damage to the mice's dopaminergic neurons was detected using immunohistochemical staining and western blotting methods. In vitro, inflammatory mediators (IL-6, TNF-α, iNOS and COX-2) and anti-inflammatory factors (Arg-1, Ym-1, CD206 and IL-10) were detected using RT-PCR, ELISA and immunofluorescence. Inflammatory pathways (AKT, PPARγ and NF-κB) were delineated by RT-PCR and western blotting. Neuronal damage was detected using CCK8, LDH, and flow cytometry assays. RESULTS: HCA2-/- increases mice susceptibility to dopaminergic neuronal injury, motor deficits, and inflammatory responses. Mechanistically, HCA2 activation in microglia promotes anti-inflammatory microglia and inhibits pro-inflammatory microglia by activating AKT/PPARγ and inhibiting NF-κB signaling pathways. Further, HCA2 activation in microglia attenuates microglial activation-mediated neuronal injury. Moreover, nicotinic acid (NA), a specific agonist of HCA2, alleviated dopaminergic neuronal injury and motor deficits in PD mice by activating HCA2 in microglia in vivo. CONCLUSIONS: Niacin receptor HCA2 modulates microglial phenotype to inhibit neurodegeneration in LPS-induced in vivo and in vitro models.

Double-Eyelid Blepharoplasty: Dermis-Outer Orbicularis Fascia-Orbicularis-Levator Fixation Technique with Preorbicular Venous Network Preservation.

BACKGROUND: This article presents a new method using a dermis-outer orbicularis fascia-orbicularis-levator (DOOL) fixation technique for double-eyelid blepharoplasty. METHODS: Our surgical technique preserves the preorbicular venous network (POVN) and uses mattress sutures to fix the dermis, outer fascia of the orbicularis oculi muscle, and orbicularis oculi muscle with pretarsal levator aponeurosis (DOOL). Between January 2016 and July 2018, 335 patients were treated with this POVN-preserving DOOL technique (321 women and 14 men; mean age, 29.6 y). The patients were followed up for 6-30 months. The complications were documented, and the overall outcomes of the upper eyelid folds were evaluated by both surgeons and patients as good, fair, or poor. RESULTS: Among 335 patients, 307 (91.6%) had good results, 17 (5.1%) had fair results, and 11 (3.3%) had poor results. Postoperative complications included partial (n=4) or complete (n=3) loss of the double-eyelid line and asymmetric folds (n=4). Hypertrophic/depressed scars did not occur. CONCLUSIONS: With less invasiveness and secure internal fixation, the DOOL fixation technique with POVN preservation can achieve a stable and natural double-eyelid appearance. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

The condensin subunits SMC2 and SMC4 interact for correct condensation and segregation of mitotic maize chromosomes.

Structural Maintenance of Chromosomes 2 (SMC2) and Structural Maintenance of Chromosomes 4 (SMC4) are the core components of the condensin complexes, which are required for chromosome assembly and faithful segregation during cell division. Because of the crucial functions of both proteins in cell division, much work has been done in various vertebrates, but little information is known about their roles in plants. Here, we identified ZmSMC2 and ZmSMC4 in maize (Zea mays) and confirmed that ZmSMC2 associates with ZmSMC4 via their hinge domains. Immunostaining revealed that both proteins showed dynamic localization during mitosis. ZmSMC2 and ZmSMC4 are essential for proper chromosome segregation and for H3 phosphorylation at Serine 10 (H3S10ph) at pericentromeres during mitotic division. The loss of function of ZmSMC2 and ZmSMC4 enlarges mitotic chromosome volume and impairs sister chromatid separation to the opposite poles. Taken together, these findings confirm and extend the coordinated role of ZmSMC2 and ZmSMC4 in maintenance of normal chromosome architecture and accurate segregation during mitosis.

High NOV/CCN3 expression during high-fat diet pregnancy in mice affects GLUT3 expression and the mTOR pathway.

We investigated the expression levels of nephroblastoma overexpressed [NOV or CCN3 (cellular communication network factor 3)] in the serum and placenta of pregnant women and of pregnant mice fed a high-fat diet (HFD), and its effect on placental glucose transporter 3 (GLUT3) expression, to examine its role in gestational diabetes mellitus (GDM). NOV/CCN3 expression was increased in the mouse serum during pregnancy. At gestational day 18, NOV/CCN3 protein expression was increased in the serum and placenta of the HFD mice compared with that of mice fed a normal diet. Compared with non-GDM patients, the patients with GDM had significantly increased serum NOV/CCN3 protein expression and placental NOV/CCN3 mRNA expression. Therefore, we hypothesized that NOV/CCN3 signaling may be involved in the pathogenesis of GDM. We administered NOV/CCN3 recombinant protein via intraperitoneal injections to pregnant mice fed HFD or normal diet. NOV/CCN3 overexpression led to glucose intolerance. Combined with the HFD, NOV/CCN3 exacerbated glucose intolerance and caused insulin resistance. NOV/CCN3 upregulates GLUT3 expression and affects the mammalian target of rapamycin (mTOR) pathway in the GDM environment in vivo and in vitro. In summary, our results demonstrate, for the first time, the molecular mechanism of NOV/CCN3 signaling in maternal metabolism to regulate glucose balance during pregnancy. NOV/CCN3 may be a potential target for detecting and treating GDM.NEW & NOTEWORTHY NOV/CCN3 regulates glucose homeostasis in mice during pregnancy. NOV/CCN3 upregulates GLUT3 expression and affects the mTOR pathway in the GDM environment in vivo and in vitro.

Secondary Upper Blepharoplasty: Converting Static Folds Into Dynamic Folds.

BACKGROUND: For the patients seeking secondary upper blepharoplasty, a static double-eyelid fold featuring an immobile lower flap and depression of the fold is common. OBJECTIVES: In this study, the authors propose a novel technique of reconstructing pretarsal tissue defects (PTDs) to converting static folds to dynamic folds. METHODS: A total of 203 patients with static folds underwent revision surgery. After complete adhesion release of the lower flap, a PTD was identified, which was defined as an area deficient of orbicularis oculi muscle in front of the tarsal plate. If the width of the PTD was over 2 mm, tissue transfer was performed to reconstruct the PTD, usually with a free retro-orbicularis oculus fat graft or a pretarsal orbicularis oculi flap. RESULTS: Among the 105 patients with severe static folds, 67 received retro-orbicularis oculus fat grafts and 38 received orbicularis oculi muscle flaps. This technique converted a static fold into a dynamic fold. The surgery satisfaction rate was 86.7%. Complications included partial fold loss (n = 7, 3.4%), complete fold loss (n = 3, 1.5%), sunken upper eyelids (n = 5, 2.5%), multiple folds (n = 3, 1.5%), an unnatural curve of the double fold (n = 5, 2.5%), and asymmetric folds (n = 4, 2.0%). CONCLUSIONS: To convert a static fold to a dynamic fold, we devised a technique that releases adhesion of the lower flap and reconstructs the PTD with retro-orbicularis oculus fat graft or an orbicularis oculi muscle flap. Our study achieved a high patient satisfaction rate, and the resulting fold mimicked the dynamics of the congenital double-eyelid fold.

Role of Pyrogenic Carbon in Parallel Microbial Reduction of Nitrobenzene in the Liquid and Sorbed Phases.

Surface functional groups and graphitic carbons make up the electroactive components of pyrogenic carbon. The role of pyrogenic carbon with different contents of electroactive components in mediating electron transfer in biochemical reactions has not been systematically studied. Here, we determined the electron exchange capacity (EEC) of pyrogenic carbon to be 0.067-0.120 mmol e-·(g of pyrogenic carbon)-1, and the maximum electrical conductivity (EC) was 4.85 S·cm-1. Nitrobenzene was simultaneously reduced in both the liquid and sorbed phases by Shewanella oneidensis MR-1 in the presence of pyrogenic carbon. Pyrogenic carbon did not affect the aqueous nitrobenzene reduction, and the reduction of sorbed nitrobenzene was much slower than that of the aqueous species. Enhancing contents of oxygenated functional moieties in pyrogenic carbon with HNO3 oxidation elevated bioreduction rates of the aqueous and sorbed species. Anthraquinone groups were deemed as the most likely oxygenated functional redox compounds on the basis of both voltammetric curve tests and spectroscopic analysis. The reactivity of pyrogenic carbon in mediating the reduction of sorbed nitrobenzene was positively correlated with its EC, which was demonstrated to be related to condensed aromatic structures. This work elucidates the mechanism for pyrogenic carbon-mediated biotransformation of nitrobenzene and helps properly evaluate the role of pyrogenic carbon in biogeochemical redox processes happening in nature.

Impact of GPR1 signaling on maternal high-fat feeding and placenta metabolism in mice.

Chemerin and G protein-coupled receptor 1 (GPR1) are increased in serum and placenta in mice during pregnancy. Interestingly, we observed increased serum chemerin levels and decreased GPR1 expression in placenta of high-fat-diet-fed mice compared with chow-fed mice at gestational day 18. GPR1 protein and gene levels were significantly decreased in gestational diabetes mellitus (GDM) patient placentas. Therefore, we hypothesized that chemerin/GPR1 signaling might participate in the pathogenic mechanism of GDM. We investigated the role of GPR1 in carbohydrate homeostasis during pregnancy using pregnant mice transfected with small interfering RNA for GPR1 or a negative control. GPR1 knockdown exacerbated glucose intolerance, disrupted lipid metabolism, and decreased ß-cell proliferation and insulin levels. Glucose transport protein-3 and fatty acid binding protein-4 were downregulated with reducing GPR1 in vivo and in vitro via phosphorylated AKT pathway. Taken together, our findings first demonstrate the expression of GPR1, the characterization of its direct biological effects in humans and mice, as well as the molecular mechanism that indicates the role of GPR1 signaling in maternal metabolism during pregnancy, suggesting a novel feedback mechanism to regulate glucose balance during pregnancy, and GPR1 could be a potential target for the detection and therapy of GDM.

p62/SQSTM1 interacts with vimentin to enhance breast cancer metastasis.

The signalling adaptor p62 is frequently overexpressed in numerous cancer types. Here, we found that p62 expression was elevated in metastatic breast cancer and its overexpression correlated with reduced metastasis- and relapse-free survival times. Analysis of p62 expression in breast cancer cell lines demonstrated that high p62 expression was associated with the invasive phenotypes of breast cancer. Indeed, silencing p62 expression attenuated the invasive phenotypes of highly metastatic cells, whereas overexpressing p62 promoted the invasion of non-metastatic cells in in vitro microfluidic model. Moreover, MDA-MB-231 cells with p62 depletion which were grown in a three-dimensional culture system exhibited a loss of invasive protrusions. Consistently, genetic ablation of p62 suppressed breast cancer metastasis in both zebrafish embryo and immunodeficient mouse models, as well as decreased tumourigenicity in vivo. To explore the molecular mechanism by which p62 promotes breast cancer invasion, we performed a co-immunoprecipitation-mass spectrometry analysis and revealed that p62 interacted with vimentin, which mediated the function of p62 in promoting breast cancer invasion. Vimentin protein expression was downregulated upon p62 suppression and upregulated with p62 overexpression in breast cancer cells. Linear regression analysis of clinical breast cancer specimens showed a positive correlation between p62 and vimentin protein expression. Together, our findings provide strong evidence that p62 functions as a tumour metastasis promoter by binding vimentin and promoting its expression. This finding might help to develop novel molecular therapeutic strategies for breast cancer metastasis treatment.

Reduction of NANOG Mediates the Inhibitory Effect of Aspirin on Tumor Growth and Stemness in Colorectal Cancer.

BACKGROUND/AIMS: Cancer stem cells (CSCs) are considered to be responsible for tumor relapse and metastasis, which serve as a potential therapeutic target for cancer. Aspirin has been shown to reduce cancer risk and mortality, particularly in colorectal cancer. However, the CSCs-suppressing effect of aspirin and its relevant mechanisms in colorectal cancer remain unclear. METHODS: CCK8 assay was employed to detect the cell viability. Sphere formation assay, colony formation assay, and ALDH1 assay were performed to identify the effects of aspirin on CSC properties. Western blotting was performed to detect the expression of the stemness factors. Xenograft model was employed to identify the anti-cancer effects of aspirin in vivo. Unpaired Student t test, ANOVA test and Kruskal-Wallis test were used for the statistical comparisons. RESULTS: Aspirin attenuated colonosphere formation and decreased the ALDH1 positive cell population of colorectal cancer cells. Aspirin inhibited xenograft tumor growth and reduced tumor cells stemness in nude mice. Consistently, aspirin decreased the protein expression of stemness-related transcription factors, including c-Myc, OCT4 and NANOG. Suppression of NANOG blocked the effect of aspirin on sphere formation. Conversely, ectopic expression of NANOG rescued the aspirin-repressed sphere formation, suggesting that NANOG is a key downstream target. Moreover, we found that aspirin repressed NANOG expression in protein level by decreasing its stability. CONCLUSION: We have provided new evidence that aspirin attenuates CSC properties through down-regulation of NANOG, suggesting aspirin as a promising therapeutic agent for colorectal cancer treatment.

RUVBL1-ITFG1 interaction is required for collective invasion in breast cancer.

BACKGROUND: The mechanisms of breast cancer collective invasion are poorly understood limiting the metastasis therapy. The ATPase RUVBL1 is frequently overexpressed in various cancers and plays a crucial role in oncogenic process. We further investigated the role of RUVBL1 in promoting collective invasion and uncovered that targeting RUVBL1 could inhibit metastatic progression. METHODS: The expression levels of RUVBL1 and ITFG1 were examined by Western blot and qRT-PCR. Co-localization and interaction of RUVBL1 and ITFG1 were determined by immunofluorescence and co-immunoprecipitation. The invasive ability was examined by transwell assay and microfluidic assay. The metastatic and tumorigenic abilities of breast cancer cells were revealed in BALB/c nude mice by xenograft and tail vein injection. RESULTS: ATPase RUVBL1 is highly expressed in breast cancer and predicts the poor prognosis. Elevated expression of RUVBL1 is found in high metastatic breast cancer cells. Silencing RUVBL1 suppresses cancer cell expansion and invasion in vitro and in vivo. RUVBL1 interacts with a conserved transmembrane protein ITFG1 in cytoplasm and plasma membrane to promote the collective invasion. Using a microfluidic model, we demonstrated that silencing RUVBL1 or ITFG1 individually compromises collective invasion of breast cancer cells. CONCLUSION: RUVBL1 is a vital regulator for collective invasion. The interaction between RUVBL1 and ITFG1 is required for breast cancer cell collective invasion and progression. GENERAL SIGNIFICANCE: Targeting collective invasion promoted by RUVBL1-ITFG1 complex provides a novel therapeutic strategy to improve the prognosis of invasive breast cancer.

SOX1 down-regulates ß-catenin and reverses malignant phenotype in nasopharyngeal carcinoma.

BACKGROUND: Aberrant activation of the Wnt/ß-catenin signaling pathway is an important factor in the development of nasopharyngeal carcinoma (NPC). Previous studies have demonstrated that the developmental gene sex-determining region Y (SRY)-box 1 (SOX1) inhibits cervical and liver tumorigenesis by interfering with the Wnt/ß-catenin signaling pathway. However, the role of SOX1 in NPC remains unclear. This study investigates the function of SOX1 in NPC pathogenesis. RESULTS: Down-regulation of SOX1 was detected in NPC cell lines and tissues. Besides, quantitative methylation-specific polymerase chain reaction revealed that SOX1 promoter was hypermethylated in NPC cell lines. Ectopic expression of SOX1 in NPC cells suppressed colony formation, proliferation and migration in vitro and impaired tumor growth in nude mice. Restoration of SOX1 expression significantly reduced epithelial-mesenchymal transition, enhanced cell differentiation and induced cellular senescence. Conversely, transient knockdown of SOX1 by siRNA in these cells partially restored cell proliferation and colony formation. Notably, SOX1 was found to physically interact with ß-catenin and reduce its expression independent of proteasomal activity, leading to inhibition of Wnt/ß-catenin signaling and decreased expression of downstream target genes. CONCLUSIONS: SOX1 decreases the expression of ß-catenin in a proteasome-independent manner and reverses the malignant phenotype in NPC cells.

Dissemination of antibiotic resistance genes is regulated by iron oxides: Insight into the influence on bacterial transformation.

The transportation of antibiotic resistance genes (ARGs) in manure-soil-plant continuums poses risks to human health. Horizontal gene transfer, particularly for bacterial transformation, is an important way for ARG dissemination. As crucial components in soils, iron oxides impacted the fates of various abiotic and biotic contaminants due to their active properties. However, whether they can influence the transformation of ARGs is unknown, which waits to be figured out to boost the assessment and control of ARG spread risks. In this study, we have investigated the effects of goethite, hematite, and magnetite (0-250 mg/L, with sizes < 100 nm and > 100 nm) on the transfer of ampicillin resistance genes to Escherichia coli cells. At lower iron oxide concentrations, the transformation of ARGs was first facilitated (transformation frequency reached up to 3.38-fold higher), but the facilitating effects gradually weakened and eventually disappeared as concentrations further increased. Particle size and iron oxide type were not the universal determinants controlling the transformation. At lower concentrations, iron oxides interacted with proteins and phospholipids in E. coli envelope structures, and induced the overgeneration of intracellular reactive oxygen species. Consequently, they led to pore formation and permeability enhancement on the cell membrane, thus promoting the transformation. The facilitation was also associated with the carrier-like effect of iron oxides for antibiotic resistance plasmids. At higher concentrations, the weakened facilitations were attributed to the aggregation of iron oxides. In this study, we highlight the crucial roles of the concentrations (contents) of iron oxides on the dissemination of ARGs in soils; this study may serve as a reference for ARG pollution control in future agricultural production.

Prolyl isomerase Pin1 sculpts the immune microenvironment of colorectal cancer.

Pin1, a peptide prolyl cis-trans isomerase, is overexpressed and/or overactivated in many human malignancies. However, whether Pin1 regulates the immunosuppressive TME has not been well defined. In this study, we detected the effect of Pin1 on immune cells and immune checkpoint PD-L1 in the TME of CRC and explored the anti-tumor efficacy of Pin1 inhibitor ATRA combined with PD-1 antibody. We found that Pin1 facilitated the immunosuppressive TME by raising the proportion of myeloid-derived suppressor cells (MDSCs) and declining the percentage of CD8+ T cells and CD4+ T cells. Pin1 restrained PD-L1 protein expression in CRC cells and the effect was tempered by endoplasmic reticulum (ER) stress inducers. Mechanically, Pin1 overexpression decreased the stability of PD-L1 and promoted its degradation by mitigating ER stress. Silencing or inhibiting Pin1 promoted PD-L1 protein expression by inducing ER stress. Hence, Pin1 inhibitor ATRA enhanced the anti-tumor efficacy of PD-1 antibody in the CRC allograft by upregulating PD-L1. Our results reveal the critical and pleiotropic effects of Pin1 on managing the immune cells and immune checkpoint PD-L1 in the TME of CRC, providing a new promising candidate for combination with immunotherapy.

Potential interaction mechanisms between PAHs and glomalin related-soil protein (GRSP).

Glomalin-related soil protein (GRSP) has gained widespread attention because of its benefits to carbon sequestration, improving soil quality and fixing heavy metals. However, studies on how GRSP affects the environmental fate of organic contaminants are scarce. In this study, different types of GRSPs were isolated from forest soils and characterized to study the binding of GRSPs and PAHs under different environmental conditions. The results indicated that GRSPs contain abundant functional groups (such as -NH, -COOH, and CO) and material composition, like humic acid, proteins, and lipids. For the tested GRSPs, EE-GRSP has lower DOC, SUVA260 and SUVA280 values, as well as higher E2/E3 values, indicating that EE-GRSP has lower hydrophobicity and molecular weight. These properties can lead to strong interactions between GRSP and PAHs, especially with benzopyrene, which has a high Kow and Ksw and a large molecular size, with binding constants ranging from 16,119 to 163,697 L·kg-1. Furthermore, low pH (pH = 3) and temperature (15 °C) could increase GRSP's aggregation, enhance the GRSP binding ability with PAHs, whose binding constants were 11,595 and 5067.3 L·kg-1. Therefore, the binding between GRSP and PAHs may lead to changes in the fate of PAHs in the soil and affect the environmental risk of PAHs. The results presented here will deepen our understanding of the environmental function of GRSPs and provide a theoretical basis to further elucidate the mechanisms of GRSPs and organic pollutants.

Conductive black carbon promoted biotransformation of undissolved 2, 2'-dinitrobiphenyl by mediating electron transfer.

With low bioaccessbility, persistence of the undissolved organic pollutants in soil and sediments poses threat to health of the resident. Although ubiquitous black carbon catalyzes a wide range of biogeochemical reactions in nature, its role in biotransformation of the compounds in non-aqueous phase like 2, 2'-nitrobiphenyl remains unclear. Reduction rate constants of 2, 2'-dinitrobiphenyl by Shewanella oneidensis MR-1 increased from 0.0044 h-1 by 7-fold to 0.035 h-1 in the presence of black carbons produced at pyrolysis temperature of 250-900 °C. Accordingly, electrical conductivity of black carbon was enhanced from 0 to 5.56 S∙cm-1. The reactivity of black carbon for catalyzing the biotransformation positively correlated with its electrical conductivity (R2 > 0.89), which was strongly associated with conductive graphitic clusters in it. The surface oxygenated groups in black carbon were likely not involved in the bioreduction. This work attaches importance to role of the ubiquitous black carbon in natural biotransformation of the undissolved pollutants, and elucidates new mechanism for the biotransformation.

Juglone Inhibits Tumor Metastasis by Regulating Stemness Characteristics and the Epithelial-to-Mesenchymal Transition in Cancer Cells both in Vitro and in Vivo.

BACKGROUND: The stemness characteristics of cancer cells, such as self-renewal and tumorigenicity, are considered to be responsible, in part, for tumor metastasis. Epithelial-to-mesenchymal transition (EMT) plays an important role in promoting both stemness and tumor metastasis. Although the traditional medicine juglone is thought to play an anticancer role by affecting cell cycle arrest, induction of apoptosis, and immune regulation, a potential function of juglone in regulating cancer cell stemness characteristics remains unknown. METHODS: In the present study, tumor sphere formation assay and limiting dilution cell transplantation assays were performed to assess the function of juglone in regulating maintenance of cancer cell stemness characteristics. EMT of cancer cells was assessed by western blot and transwell assay in vitro, and a liver metastasis model was also performed to demonstrate the effect of juglone on colorectal cancer cells in vivo. RESULTS: Data gathered indicates juglone inhibits stemness characteristics and EMT in cancer cells. Furthermore, we verified that metastasis was suppressed by juglone treatment. We also observed that these effects were, in part, achieved by inhibiting Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (Pin1). CONCLUSIONS: These results indicate that juglone inhibits maintenance of stemness characteristics and metastasis in cancer cells.

Oral administration of Limonin (LM) exerts neuroprotective effects by inhibiting neuron autophagy and microglial activation in 6-OHDA-injected rats.

Parkinson's disease (PD) is a neurodegenerative disorder that occurs most frequently in middle-aged and elderly people. It is characterized by an insidious onset and a complex etiology, and no effective treatment has been developed. The primary characteristic of PD is the degenerative death of midbrain dopaminergic neurons. The excessive autophagy of neurons and hyperactivation of microglia were shown to be involved in the apoptosis of dopaminergic neurons. Limonin (LM), a type of pure natural compound present in grapefruit or citrus fruits (e. g., lemon, orange) has been reported to inhibit apoptosis and inflammation. However, its role and mechanism of action in PD are unclear. In this study, we explored the effect and mechanism of action of LM in PD. In vivo experiments revealed that LM ameliorated 6-OHDA-induced reduced motor activity and PD-related pathological damage in rats. In vitro experiments revealed that LM inhibited the 6-OHDA-induced apoptosis of PC12 cells by inhibiting the excessive autophagy of neurons. In addition, LM inhibited microglial inflammation by activating the AKT/Nrf-2/HO-1 pathway and protected neurons against microglial inflammation-mediated neurotoxicity. In conclusion, the findings of this experiment demonstrated that LM exerted neuroprotective effects by inhibiting neuronal autophagy-mediated apoptosis and microglial activation in 6-OHDA-injected rats, thus indicating that LM can serve as a candidate for PD by targeting neuroinflammation and neuronal autophagy to inhibit neuronal apoptosis.

Notopterol inhibits LPS-induced inflammation in BV-2 cells via AKT/Nrf2/HO-1 signaling axis.

Accumulating research has indicated that inordinate activation of microglia releases inflammatory cytokines, damages neurons, and causes neuroinflammation, which eventually could lead to neurodegenerative diseases such as Parkinson's disease and Huntington's disease, etc. Notopterol (NOT) has anti-inflammatory and anti-oxidant functions in boundary tissues, but the effects of NOT on neuroinflammation have not been covered. Therefore, this study attempts to investigate the effect of NOT on neuroinflammation and the underlying mechanisms. According to the findings, NOT dramatically decreased the expression of pro-inflammatory mediators (interleukin-6 (IL-6), inducible nitric-oxide synthase (iNOS), tumor necrosis factor-α (TNF-α), and Cyclooxygenase-2 (COX-2)) in LPS-exposed BV-2 cells. Western blot analysis revealed that NOT could promote the activation of AKT/Nrf2/HO-1 signaling pathway. Further studies have shown that anti-inflammatory property of NOT was inhibited by MK2206 (an AKT inhibitor), RA (an Nrf2 inhibitor), and SnPP IX (an HO-1 inhibitor). In addition, it was also discovered that NOT could weaken the damage of LPS to BV-2 cells and improve their survival rate. As a result, our results imply that NOT inhibits the inflammatory response of BV-2 cells through the AKT/Nrf2/HO-1 signaling axis and exerts a neuroprotective effect by inhibiting the activation of BV-2 cells.