Customized Self-Assembled Gold Nanoparticle-DNA Origami Composite Templates for Shape-Directed Growth of Plasmonic Structures.

The metal plasmonic nanostructure has the optical property of plasmon resonance, which holds great potential for development in nanophotonics, bioelectronics, and molecular detection. However, developing a general and straightforward method to prepare metal plasmonic nanostructures with a controllable size and morphology still poses a challenge. Herein, we proposed a synthesis strategy that utilized a customizable self-assembly template for shape-directed growth of metal structures. We employed gold nanoparticles (AuNPs) as connectors and DNA nanotubes as branches, customizing gold nanoparticle-DNA origami composite nanostructures with different branches by adjusting the assembly ratio between the connectors and branches. Subsequently, various morphologies of plasmonic metal nanostructures were created using this template shape guided strategy, which exhibited enhancement of surface-enhanced Raman scattering (SERS) signals. This strategy provides a new approach for synthesizing metallic nanostructures with multiple morphologies and opens up another possibility for the development of customizable metallic plasmonic structures with broader applications.

Clinical outcome and molecular landscape of patients with ARID1A-loss gastric cancer.

Chromatin remodelers are commonly altered in human cancer. The mutation of AT-rich interactive domain 1A (ARID1A) in gastric cancer (GC), a component of the SWI/SNF chromatin remodeling complex, was proven associated with treatment response in our previous study. However, ARID1A loss of function was caused not only by mutations but also copy number deletions. The clinicopathologic, genomic, and immunophenotypic correlates of ARID1A loss is largely uncharacterized in GC. Here, 819 patients with clinicopathological information and sequencing data or formalin-fixed paraffin-embedded tissues from four cohorts, Zhongshan Hospital (ZSHS) cohort (n = 375), The Cancer Genome Atlas (TCGA) cohort (n = 371), Samsung Medical Center (SMC) cohort (n = 53), and ZSHS immunotherapy cohort (n = 20), were enrolled. ARID1A loss was defined by genome sequencing or deficient ARID1A expression by immunohistochemistry. We found that ARID1A mutation and copy number deletion were enriched in GC with microsatellite instability (MSI) and chromosomal-instability (CIN), respectively. In the TCGA and ZSHS cohorts, only CIN GC with ARID1A loss could benefit from fluorouracil-based adjuvant chemotherapy. In the SMC and ZSHS immunotherapy cohorts, ARID1A loss exhibited a tendency of superior responsiveness and indicated favorable overall survival after anti-PD-1 immunotherapy. ARID1A-loss tumors demonstrated elevated mutation burden, neoantigen load, and interferon gamma pathway activation. Moreover, in CIN GC, ARID1A loss was correlated with higher homologous recombination deficiency. ARID1A loss defines a distinct subtype of GC characterized by high levels of genome instability, neoantigen formation, and immune activation. These tumors show sensitivity to both chemotherapy and anti-PD-1 immunotherapy. This study provides valuable insights for precision treatment strategies in GC.

Lipid transport protein ORP2A promotes glucose signaling by facilitating RGS1 degradation.

Heterotrimeric GTP-binding proteins (G proteins) are a group of regulators essential for signal transmission into cells. Regulator of G protein signaling 1 (AtRGS1) possesses intrinsic GTPase-accelerating protein (GAP) activity and could suppress G protein and glucose signal transduction in Arabidopsis (Arabidopsis thaliana). However, how AtRGS1 activity is regulated is poorly understood. Here, we identified a knockout mutant of oxysterol binding protein-related protein 2A, orp2a-1, which exhibits similar phenotypes to the arabidopsis g-protein beta 1-2 (agb1-2) mutant. Transgenic lines overexpressing ORP2A displayed short hypocotyls, a hypersensitive response to sugar, and lower intracellular AtRGS1 levels than the control. Consistently, ORP2A interacted with AtRGS1 in vitro and in vivo. Tissue-specific expression of 2 ORP2A alternative splicing isoforms implied functions in controlling organ size and shape. Bioinformatic data and phenotypes of orp2a-1, agb1-2, and the orp2a-1 agb1-2 double mutant revealed the genetic interactions between ORP2A and Gß in the regulation of G protein signaling and sugar response. Both alternative protein isoforms of ORP2A localized in the endoplasmic reticulum (ER), plasma membrane (PM), and ER-PM contact sites and interacted with vesicle-associated membrane protein-associated protein 27-1 (VAP27-1) in vivo and in vitro through their two phenylalanines in an acidic track-like motif. ORP2A also displayed differential phosphatidyl phosphoinositide binding activity mediated by the pleckstrin homology domain in vitro. Taken together, the Arabidopsis membrane protein ORP2A interacts with AtRGS1 and VAP27-1 to positively regulate G protein and sugar signaling by facilitating AtRGS1 degradation.

AMPK hyperactivity maintains the survival of vasculogenic T cells in patients with Takayasu's arteritis.

OBJECTIVES: Takayasu's arteritis (TAK) is a progressive autoimmune vasculitis that mainly affects the aorta and its major branches. While recent studies have identified proinflammatory T cells, including Th1 and Th17 cells, as the dominant infiltrates in the arterial adventitia, mechanisms underpinning the maintenance of such vasculogenic T cells remain obscure. METHODS: 75 patients with TAK and 30 age-matched healthy controls were enrolled in this study. CD4 T cells from TAK patients were activated with anti-CD3/CD28 beads to mimic vasculogenic T cells. The survival of T cells was detected by quantifying Annexin-V+7-AAD+ fractions. Expression and activity of AMP-activated protein kinase (AMPK) were determined using phosflow cytometry and immunoblots. Specific inhibitors and shRNA were applied to block the function of AMPK and Notch1, while erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were used to reflect the disease activity of TAK patients. RESULTS: T cells from TAK patients undergo spontaneous differentiation into vasculogenic proinflammatory T cells with prolonged survival capacity. Mechanistic explorations uncover AMPK hyperactivity in such T cells from TAK patients, promoting mitochondrial metabolism and their survival. Such AMPK hyperactivity results from the robust Notch1 activity in TAK T cells. Accordingly, T cell-intrinsic phosphor-AMPK reflects the disease activity in clinical TAK patients. CONCLUSIONS: AMPK hyperactivity is essential for maintaining the vasculogenic proinflammatory T cells in TAK patients, serving as a promising therapeutic target for TAK management.

Astragalin ameliorates renal injury in diabetic mice by modulating mitochondrial quality control via AMPK-dependent PGC1α pathway.

Diabetic kidney disease (DKD) is a common microvascular complication of diabetes mellitus, and oxidative stress and mitochondrial dysfunction play an important role in this process. It has been shown that aldose reductase (ALR2) catalyzes NADPH-dependent reduction of glucose to sorbitol, resulting in oxidative stress and mitochondrial dysfunction in diabetic patients. Astragalin (AG), a flavonoid extracted from Thesium chinense Turcz., shows an inhibitory activity on ALR2. In this study, we investigated the therapeutic effects of AG against renal injury in streptozocin (STZ)-induced diabetic mouse model. Diabetic mice were orally administered AG (5, 10 mg·kg-1·d-1) for 4 weeks. We showed that AG treatment greatly improved the proteinuria and ameliorated renal pathological damage without affecting the elevated blood glucose in diabetic mice. Furthermore, AG treatment significantly suppressed highly activated ALR2, and reduced oxidative stress in the kidney of diabetic mice and in high glucose and lipids-stimulated HK2 cells in vitro. We demonstrated that AG treatment modulated mitochondrial quality control and ameliorated apoptosis, boosting mitochondrial biogenesis, maintaining mitochondrial dynamic homeostasis, and improving energy metabolism disorder in vivo and in vitro. In high glucose and lipids-stimulated HK2 cells, we found that AG (20 µM) restored the phosphorylation level of AMPK, and upregulated the expression and transcriptional activity of PGC1α, whereas treatment with H2O2, blockade of AMPK with Compound C or knockdown of AMPKα with siRNA abolished the protective effect of AG on mitochondrial function, suggesting that antioxidant effects and activation of AMPK-dependent PGC1α pathway might be the molecular mechanisms underlying the protective effects of AG on mitochondrial quality control. We conclude that AG could be a promising drug candidate for the treatment of diabetic renal injury through activating AMPK.

Metabolomics study based on GC-MS reveals a protective function of luteolin against glutamate-induced PC12 cell injury.

Oxidative stress response is closely related to neurodegenerative diseases. This study aimed to investigate the cytoprotective effects of luteolin on glutamate-induced oxidative stress injury in PC12 cells. GC-MS combined with multivariate statistical approaches was used to perform metabolomics studies to assess the possible mechanisms. Our results identified 23 metabolites as differential expressed metabolites in the glutamate group, including cysteine content in cells that decreased drastically. This suggests that glutathione synthesis, which balances the redox state of cells, was affected. Luteolin inhibits the reduction in viability in glutamate-induced PC12 cells and regulates 13 differential expressed metabolites in glutamate-induced cell damage. These metabolites associated with luteolin included glycine, serine, and threonine metabolism; glyoxylate and dicarboxylate metabolism; aminoacyl-tRNA biosynthesis; cysteine and methionine metabolism; inositol phosphate metabolism; and starch and sucrose metabolism. In summary, the systemic antioxidant capacity of luteolin in PC12 cells is related to its regulation of amino acid, glucose, and nucleotide metabolism pathways.

Dual-functional lanthanide-MOF probe nanocomposite based on hydroxyapatite nanowires as fluorescent sensor for ascorbic acid.

A dual-functional lanthanide-MOF nanocomposite probe was designed and constructed for the detection of ascorbic acid (AA). The magnetically functionalized hydroxyapatite nanowires are selected as the carriers and simultaneously loaded with ciprofloxacin (CIP) and terbium metal organic framework to form the internal reference fluorescence probe nanocomposite (Fe3O4-HAPNWs-Tb/MOF-CIP). This dual-functional lanthanide-MOF probe not only combines the respectively unique fluorescence properties of lanthanide MOFs and CIP, but also takes full advantage of the rapid separation properties of the magnetic component. Structural and spectroscopic characterization results have demonstrated the successful synthesis of probe material and the fluorescence mechanism. At a suitable excitation wavelength (295 nm), the probe can simultaneously emit characteristic fluorescence of CIP (445 nm) and Tb3+ (543 nm). In the presence of AA, the ratio of I543/I445 decreases rapidly with increasing of AA concentration. The linear range of determination is 0.3-40 µM with a detection limit of 20.4 nM. The contents of AA in vitamin C tablets and four fruit juice samples were detected by the composite probe. The spiked recoveries ranged from 82.6 to 104.2% with relative standard deviations (RSD) less than 2.1%, revealing the practical application value of the developed sensor in healthcare and food fields. A novel internal reference fluorescence sensor (Fe O -HAPNWs-Tb/MOF-CIP) was constructed for detecting ascorbic acid by solvothermal and self-assembly techniques, showing excellent selectivity and sensitivity based on the different responses of Tb/MOF and CIP to the target.

Clinical characteristics and prognosis of patients with idiopathic membranous nephropathy with kidney tubulointerstitial damage.

BACKGROUND: To investigate the clinical and kidney pathological features and prognosis of idiopathic membranous nephropathy (IMN) with kidney tubulointerstitial damage (TID). METHODS: Based on the presence or absence of kidney TID by kidney biopsy, 300 patients diagnosed with IMN were categorized into non-TID (TID-) and tubulointerstitial injury (TID+) groups. The clinical and pathological data were analyzed retrospectively. All patients were followed up for 6-24 months after treatment with glucocorticoids (GCs) combined with cyclophosphamide or GCs combined with calcineurin inhibitors (CNIs) to observe treatment effects on patient prognosis. RESULTS: The patients in the TID + group were older and more likely to be male. The 24-h urine protein, blood urea nitrogen, serum creatinine, cystatin C, ß2-microglobulin, and antiphospholipase A2 receptor antibody levels were higher than those in the TID - group and the pathological manifestations were more severe. After 1 year of follow-up, the overall response rate (complete response + partial response) in the TID + group was lower (66.67% vs. 80.89%, p = .022) than in the other. After combined GC and CNI therapy, the complete remission rate in the TID + group was significantly lower than that in the TID - group (13.79% vs. 35.46%, p = .022). The 24-h urine protein level was an independent risk factor for worsening kidney condition (p = .038). CONCLUSION: Patients with IMN with TID have more severe clinical manifestations and pathological damage and lower remission rates. IMN with TID is a risk factor for worsening kidney condition; however, it is not an independent risk factor.

LncRNA WDR11-AS1 Promotes Extracellular Matrix Synthesis in Osteoarthritis by Directly Interacting with RNA-Binding Protein PABPC1 to Stabilize SOX9 Expression.

Osteoarthritis (OA) is a degenerative disease of articular cartilage that is mainly characterized by chronic and mild inflammation of the joints. Recently, many studies have reported the crucial roles of long noncoding RNAs (lncRNAs) in OA as gene transcriptional regulatory factors, diagnostic biomarkers, or therapeutic targets. However, the exact mechanisms of lncRNAs in the regulation of OA progression remain unclear. In the present study, the lncRNA WDR11 divergent transcript (lncRNA WDR11-AS1) was shown to be downregulated in osteoarthritic cartilage tissues from patients, and to promote extracellular matrix (ECM) synthesis in osteoarthritic chondrocytes with knockdown and overexpression experiments. This function of lncRNA WDR11-AS1 was linked to its ability to interact with the polyadenylate-binding protein cytoplasmic 1 (PABPC1), which was screened by RNA pulldown and mass spectrometry analyses. PABPC1 was discovered to bind ECM-related mRNAs such as SOX9, and the inhibition of PABPC1 improved the mRNA stability of SOX9 to mitigate OA progression. Our results suggest that lncRNA WDR11-AS1 has a promising inhibitory effect on inflammation-induced ECM degradation in OA by directly binding PABPC1, thereby establishing lncRNA WDR11-AS1 and PABPC1 as potential therapeutic targets in the treatment of OA.

Selenium-sensitive histone deacetylase 2 is required for forkhead box O3A and regulates extracellular matrix metabolism in cartilage.

INTRODUCTION: Selenium (Se) as well as selenoproteins are vital for osteochondral system development. Se deficiency (SeD) has a definite impact on the expression and activity of histone deacetylases (HDACs). Abnormal expression of some HDACs affects cartilage development. This current study aims to explore the relationship between differentially expressed HDACs and cartilage development, especially extracellular matrix (ECM) homeostasis maintenance, under SeD conditions. MATERIALS AND METHODS: Dark Agouti rats and C28/I2 cell line under SeD states were used to detect the differently expressed HDAC by RT-qPCR, western blotting and IHC staining. Meanwhile, the biological roles of the above HDAC in cartilage development and homeostasis maintenance were confirmed by siRNA transfection, western blotting, RNA sequence and inhibitor treatment experiments. RESULTS: HDAC2 exhibited lower expression at protein level in both animals and chondrocytes during SeD condition. The results of cell-level experiments indicated that forkhead box O3A (FOXO3A), which was required to maintain metabolic homeostasis of cartilage matrix, was reduced by HDAC2 knockdown. Meanwhile, induced HDAC2 was positively associated with FOXO3A in rat SeD model. Meanwhile, knockdown of HDAC2 and FOXO3A led to an increase of intracellular ROS level, which activated NF-κB pathway. Se supplementary significantly inhibited the activation of NF-κB pathway with IL-1ß treatment. CONCLUSION: Our results suggested that low expression of HDAC2 under SeD condition increased ROS content by decreasing FOXO3A in chondrocytes, which led to the activation of NF-κB pathway and ECM homeostasis imbalance.

Carbon dots-decorated hydroxyapatite nanowires-lanthanide metal-organic framework composites as fluorescent sensors for the detection of dopamine.

In this work, carbon dots-decorated hydroxyapatite nanowires-lanthanide metal-organic framework composites were designed and synthesized as ratiometric fluorescent probes for the detection of dopamine. The as-prepared HAPNWs-CDs-Tb/MOF were characterized by TEM, FE-SEM, and FT-IR spectral analysis, illustrating that the HAPNWs-CDs-Tb/MOF comprised hydroxyapatite nanowires that acted as a carrier to form a spinning structure of the lanthanide MOF that was decorated with carbon dots. The as-prepared HAPNWs-CDs-Tb/MOF were luminescent with the green fluorescence of Tb3+ at 543 nm and the blue fluorescence of the CDs at 426 nm as the signal response groups for the detection of DA. The sensor could detect DA in the concentration range of 0-180 µM, with a linear range of 0.04-20 µM and detection limit of 12.26 nM. The method was successfully applied to the detection of DA in human serum. The spiked recoveries were 100.8%-103.3% and the relative standard deviation (RSD) was 3.82%.

Experiences of family caregivers of patients with post-traumatic hydrocephalus from hospital to home: a qualitative study.

BACKGROUND: Post-traumatic hydrocephalus (PTH) is a complication of traumatic brain injury (TBI) that requires treatment and postoperative care. The shunt is one of the main treatments for PTH, which presents with dysfunction and infection. Considering brain injury, hydrocephalus shunt malfunction, and infection, family caregivers need to be responsible for caring for PTH patients, recognizing shunt malfunction and infection, and managing those patients accordingly from hospital to home. Understanding the experiences and needs of caregivers is beneficial for knowing their competency and quality of health care, ameliorating and ensuring future transition care. The study aimed to explore the feelings, experiences, and needs of family caregivers when caring for patients with TBI, PTH and shunts. METHODS: This was exploratory research of a purposive sample of 12 family caregivers of adult patients with TBI, PTH and shunts in five neurosurgery departments at a general hospital in Zhengzhou, Henan Province, China, using a semi-structured interview method. Data were collected from October 2021 to March 2022 before being analyzed by content analysis methods. RESULTS: Caregivers required professional and social knowledge and support in the areas of TBI, PTH and shunts, caregiving interventions, psychological care needs, and health insurance, just as caregivers do, but unlike other general caregivers, care for patients with TBI, PTH, and shunt is fraught with uncertainty and the need to manage shunt setting, and caregivers often experience 'complex emotional reaction' during the transitional period, where care needs and complex emotions may lead to a lack of caregiver confidence, which in turn may affect caregiving behaviors, and experiences that affect care may be mediated through caregiving confidence. The perceived availability of resources, particularly those that are still available to them when they return home, has a significant impact on participants' emotional response and sense of confidence. CONCLUSIONS: The emotional response and the impact of stressor caregivers after TBI, PTH, and shunt was important, and sometimes confidence in care appeared to be an intermediate and useful factor that needed to be considered as health professionals prepared to develop care resources on how to manage and empower patients with TBI, PTH, and shunt. Meanwhile, there may be gaps and inequities in supportive care for patients diagnosed with TBI, PTH, and shunt in China.

Clinical and pathological features of anti-glomerular basement membrane disease associated with membranous nephropathy: an observational study.

To investigate the clinical manifestations, pathological features, pathogenesis, treatment, and prognosis of anti-glomerular basement membrane (anti-GBM) disease with membranous nephropathy (MN). Seven patients with anti-GBM disease and concurrent MN were enrolled in this study. Control subjects included 13 patients with anti-GBM glomerulonephritis (GN) and 6 with anti-GBM disease and concurrent anti-neutrophil cytoplasmic antibodies-associated disease (anti-GBM + ANCA). Laboratory tests and pathological information were analyzed before immunosuppressive therapy or plasmapheresis administration. Prognosis was assessed in continuous follow-up. In the anti-GBM + MN group, 28.57% of patients exhibited acute kidney disease, lower than that in the anti-GBM GN group (84.62%, p = .022). None of the anti-GBM + MN or + ANCA patients exhibited hemoptysis, but 15.4% of anti-GBM GN patients did, with no significant difference (p = .720). Only 14.3% of anti-GBM + MN patients had crescentic GN. The proportion of necrosis averaged 29.0% in the anti-GBM + MN group. Survival curve analysis revealed that renal outcomes in the anti-GBM + MN group were better than those in the anti-GBM GN group (p = .019). Patients with both anti-GBM disease and MN showed atypical anti-GBM GN. They had a lower proportion of glomerular crescents and a better renal function prognosis than patients with classical anti-GBM GN. To improve renal recovery, early identification and treatment of anti-GBM disease associated with MN is needed.

Flubendazole Plays an Important Anti-Tumor Role in Different Types of Cancers.

Flubendazole, belonging to benzimidazole, is a broad-spectrum insect repellent and has been repurposed as a promising anticancer drug. In recent years, many studies have shown that flubendazole plays an anti-tumor role in different types of cancers, including breast cancer, melanoma, prostate cancer, colorectal cancer, and lung cancer. Although the anti-tumor mechanism of flubendazole has been studied, it has not been fully understood. In this review, we summarized the recent studies regarding the anti-tumor effects of flubendazole in different types of cancers and analyzed the related mechanisms, in order to provide the theoretical reference for further studies in the future.

The Role of Hydrogen Sulfide Regulation of Autophagy in Liver Disorders.

Autophagy is a complex process of degradation of senescent or dysfunctional organelles in cells. Dysfunctional autophagy is associated with many diseases such as cancers, immune dysfunction, and aging. Hydrogen sulfide (H2S) is considered to be the third gas signal molecule after nitrous oxide and carbon monoxide. In recent years, H2S has been found to have a variety of important biological functions, and plays an important role in a variety of physiological and pathological processes. In this review, we review the recent role and mechanism of H2S in regulating autophagy in liver disorders, in order to provide a basis for further research in the future.

The Pivotal Player: Components of NF-κB Pathway as Promising Biomarkers in Colorectal Cancer.

Over the last several decades, colorectal cancer (CRC) has been one of the most prevalent cancers. While significant progress has been made in both diagnostic screening and therapeutic approaches, a large knowledge gap still remains regarding the early identification and treatment of CRC. Specifically, identification of CRC biomarkers that can help with the creation of targeted therapies as well as increasing the ability for clinicians to predict the biological response of a patient to therapeutics, is of particular importance. This review provides an overview of CRC and its progression stages, as well as the basic types of CRC biomarkers. We then lay out the synopsis of signaling pathways related to CRC, and further highlight the pivotal and multifaceted role of nuclear factor (NF) κB signaling in CRC. Particularly, we bring forth knowledge regarding the tumor microenvironment (TME) in CRC, and its complex interaction with cancer cells. We also provide examples of NF-κB signaling-related CRC biomarkers, and ongoing efforts made at targeting NF-κB signaling in CRC treatment. We conclude and anticipate that with more emerging novel regulators of the NF-κB pathway being discovered, together with their in-depth characterization and the integration of large groups of genomic, transcriptomic and proteomic data, the day of successful development of more ideal NF-κB inhibitors is fast approaching.

Unveiling the Activity Origin of Iron Nitride as Catalytic Material for Efficient Hydrogenation of CO2 to C2+ Hydrocarbons.

Developing efficient catalytic materials and unveiling the active species are significant for selective hydrogenation of CO2 to C2+ hydrocarbons. Fe2 N@C nanoparticles were reported to exhibit outstanding performance toward selective CO2 hydrogenation to C2+ hydrocarbons (C2+ selectivity: 53.96 %; C2 -C4 = selectivity, 31.03 %), outperforming corresponding Fe@C. In situ X-ray diffraction, ex situ Mössbauer and X-ray photoelectron spectra revealed that iron nitrides were in situ converted to highly active iron carbides, which acted as the real active species. Moreover, the combined results of in situ diffuse reflectance infrared Fourier transform spectroscopy and control experiments suggested an in situ formed carbonyl iron-mediated conversion mechanism from iron nitrides to iron carbides.

Regulation of a PRMT5/NF-κB Axis by Phosphorylation of PRMT5 at Serine 15 in Colorectal Cancer.

The overexpression of PRMT5 is highly correlated to poor clinical outcomes for colorectal cancer (CRC) patients. Importantly, our previous work demonstrated that PRMT5 overexpression could substantially augment activation of the nuclear factor kappa B (NF-κB) via methylation of arginine 30 (R30) on its p65 subunit, while knockdown of PRMT5 showed the opposite effect. However, the precise mechanisms governing this PRMT5/NF-κB axis are still largely unknown. Here, we report a novel finding that PRMT5 is phosphorylated on serine 15 (S15) in response to interleukin-1ß (IL-1ß) stimulation. Interestingly, we identified for the first time that the oncogenic kinase, PKCι could catalyze this phosphorylation event. Overexpression of the serine-to-alanine mutant of PRMT5 (S15A), in either HEK293 cells or CRC cells HT29, DLD1, and HCT116 attenuated NF-κB transactivation compared to WT-PRMT5, confirming that S15 phosphorylation is critical for the activation of NF-κB by PRMT5. Furthermore, the S15A mutant when compared to WT-PRMT5, could downregulate a subset of IL-1ß-inducible NF-κB-target genes which correlated with attenuated promoter occupancy of p65 at its target genes. Additionally, the S15A mutant reduced IL-1ß-induced methyltransferase activity of PRMT5 and disrupted the interaction of PRMT5 with p65. Furthermore, our data indicate that blockade of PKCι-regulated PRMT5-mediated activation of NF-κB was likely through phosphorylation of PRMT5 at S15. Finally, inhibition of PKCι or overexpression of the S15A mutant attenuated the growth, migratory, and colony-forming abilities of CRC cells compared to the WT-PRMT5. Collectively, we have identified a novel PKCι/PRMT5/NF-κB signaling axis, suggesting that pharmacological disruption of this pivotal axis could serve as the basis for new anti-cancer therapeutics.

Fibroblast growth factor 21 protects against pathological cardiac remodeling by modulating galectin-3 expression.

BACKGROUND/AIMS: Fibroblast growth factor 21 (FGF21) plays a protective role in ischemia/reperfusion induced cardiac injury. However, the exact molecular mechanism of FGF21 action remains unclear. This study was designed the protective effect of FGF21 on the heart and its mechanism. METHOD: Adenovirus vector expressing FGF21 or control ß-galactosidase was injected into the myocardium of mice. Myocardial injury was observed by tissue staining and immunohistochemical staining. The expression level of caspases-3 and galectin-3 in myocardial cells were observed by immunoblotting. Then, hypoxia-induced cell model was established. Small interfering RNA (SiRNA) and plasmid were transfected into H9c2 using Lipofectamine 2000 reagent (Invitrogen). The expression levels of galectin-3, ECM and cystatin-3 in cells were observed by immunoblotting, and the relationship between fibroblast growth factor 21 and galectin-3 was analyzed. RESULT: Cell test in vitro showed that FGF21 could inhibit apoptosis and decrease the expression of ECM (ColIaI, fibronectin, and alpha-SMA) under hypoxia. Western blot data showed that hypoxia-induced cell damage increased galectin-3 levels, while FGF21 decreased galactose lectin-3 levels. In addition, inhibition of galactose agglutinin-3 expression by siRNA enhanced the cardioprotective effect of FGF21, while overexpression of galectin-3 reduced the cardioprotective effect of fibroblast growth factor 21. CONCLUSION: FGF21 may be a novel therapy for hypoxia-induced cardiac injury by regulating the expression of galectin-3.

MicroRNA-378 regulates epithelial-mesenchymal transition and metastasis of melanoma by inhibiting FOXN3 expression through the Wnt/ß-catenin pathway.

MicroRNAs (miRNAs) participate in the development and progression of melanoma. However, while dysregulation of microRNA-378 (miR-378) has been seen in various cancer types, its clinical importance and function in melanoma are poorly elucidated. In this work, miR-378 expression in melanoma and in adjacent non-cancerous tissue was evaluated with a quantitative real-time polymerase chain reaction. A series of assays (wound healing, Transwell, and nude mouse subcutaneous tumor model) were used to investigate the implications of abnormal miR-378 regulation on melanoma cell migration and invasion in vitro, and on tumorigenicity in vivo. Prediction and conformation of the miR-378 target gene was undertaken using bioinformatic analysis and luciferase reporter system. Expression of miR-378 was often increased in melanoma, and shown to potentiate its migration, invasion, and tumorigenicity. miR-378 acted, at least partially, through inhibition of the potential target FOXN3 and via Wnt/ß-catenin pathway activation. The findings indicate that miR-378 triggers melanoma development and progression. This miRNA could be a novel diagnostic and prognostic biological marker and provide utility for targeted treatment of melanoma.