Faculty Opinions recommendation of Arginase and polyamine synthesis are key factors in the regulation of experimental leishmaniasis in vivo.

: Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by the progressive loss of neurons leading to cognitive and memory decay. The main signs of AD include the irregular extracellular accumulation of amyloidbeta (Aβ) protein in the brain and the hyper-phosphorylation of tau protein inside neurons. Changes in Aβ expression or aggregation are considered key factors in the pathophysiology of sporadic and early-onset AD and correlate with the cognitive decline seen in patients with AD. Despite decades of research, current approaches in the treatment of AD are only symptomatic in nature and are not effective in slowing or reversing the course of the disease. Encouragingly, recent evidence revealed that exposure to electromagnetic fields (EMF) can delay the development of AD and improve memory. This review paper discusses findings from in vitro and in vivo studies that investigate the link between EMF and AD at the cellular and behavioural level, and highlights the potential benefits of EMF as an innovative approach for the treatment of AD.

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The methyltransferase SETD2 couples transcription and splicing by engaging mRNA processing factors through its SHI domain

Nature Communications ◽

10.1038/s41467-021-21663-w ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Saikat Bhattacharya ◽

Michaella J. Levy ◽

Ning Zhang ◽

Hua Li ◽

Laurence Florens ◽

...

Keyword(s):

Rna Splicing ◽

Rna Binding ◽

Mrna Processing ◽

Key Factors ◽

Pol Ii ◽

Mrna Transcripts ◽

Hnrnp Protein ◽

Processing Factors

AbstractHeterogeneous ribonucleoproteins (hnRNPs) are RNA binding molecules that are involved in key processes such as RNA splicing and transcription. One such hnRNP protein, hnRNP L, regulates alternative splicing (AS) by binding to pre-mRNA transcripts. However, it is unclear what factors contribute to hnRNP L-regulated AS events. Using proteomic approaches, we identified several key factors that co-purify with hnRNP L. We demonstrate that one such factor, the histone methyltransferase SETD2, specifically interacts with hnRNP L in vitro and in vivo. This interaction occurs through a previously uncharacterized domain in SETD2, the SETD2-hnRNP Interaction (SHI) domain, the deletion of which, leads to a reduced H3K36me3 deposition. Functionally, SETD2 regulates a subset of hnRNP L-targeted AS events. Our findings demonstrate that SETD2, by interacting with Pol II as well as hnRNP L, can mediate the crosstalk between the transcription and the splicing machinery.

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Targeting Erbin in B cells for therapy of lung metastasis of colorectal cancer

Signal Transduction and Targeted Therapy ◽

10.1038/s41392-021-00501-x ◽

2021 ◽

Vol 6 (1) ◽

Author(s):

Tong Shen ◽

Jing-Lin Liu ◽

Chu-Yi Wang ◽

Youlutuziayi Rixiati ◽

Shi Li ◽

...

Keyword(s):

B Cells ◽

Lung Metastasis ◽

Lung Metastases ◽

Pdz Domain ◽

Clinical Samples ◽

Key Factors ◽

Combined Use ◽

Iga Production

AbstractThe mechanisms and key factors involved in tumor environments for lung metastasis of CRC are still unclear. Here, using clinical samples from lung metastases of CRC patients, we found that intestinal immune network for IgA production was significantly dysregulated in lung metastases of CRC. Single-cell RNA sequencing discovered a subtype of B cells positive for Erbin, one member of the leucine-rich repeat and PDZ domain (LAP) family, was involved in the lung metastases. Erbin deletion in B cells suppressed lung metastasis of CRC in vivo. And, deletion of Erbin in B cells enhanced the killing effects of CD8+ T cells on tumor cells. Mechanistically, Erbin knockout attenuated TGFβ-mediated suppression of migration of CXCR5+ IgA+ cells and STAT6-mediated PD1 expression. Our study uncovered a key role of Erbin in regulating PD1+ IgA+ B cells in lung metastasis of CRC. Targeting Erbin as well as combined use of neutralizing B cells and antibodies neutralizing PD1 suppresses lung metastasis of CRC in mice, suggesting the potential option for treatment of lung metastasis of CRC.

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Towards Clinical Translation of LED-Based Photoacoustic Imaging: A Review

Sensors ◽

10.3390/s20092484 ◽

2020 ◽

Vol 20 (9) ◽

pp. 2484 ◽

Cited By ~ 10

Author(s):

Yunhao Zhu ◽

Ting Feng ◽

Qian Cheng ◽

Xueding Wang ◽

Sidan Du ◽

...

Keyword(s):

Ex Vivo ◽

Photoacoustic Imaging ◽

Imaging Techniques ◽

Clinical Translation ◽

Key Factors ◽

Pilot Studies ◽

History Of ◽

Molecular Components ◽

Clinical Potential

Photoacoustic imaging, with the capability to provide simultaneous structural, functional, and molecular information, is one of the fastest growing biomedical imaging modalities of recent times. As a hybrid modality, it not only provides greater penetration depth than the purely optical imaging techniques, but also provides optical contrast of molecular components in the living tissue. Conventionally, photoacoustic imaging systems utilize bulky and expensive class IV lasers, which is one of the key factors hindering the clinical translation of this promising modality. Use of LEDs which are portable and affordable offers a unique opportunity to accelerate the clinical translation of photoacoustics. In this paper, we first review the development history of LED as an illumination source in biomedical photoacoustic imaging. Key developments in this area, from point-source measurements to development of high-power LED arrays, are briefly discussed. Finally, we thoroughly review multiple phantom, ex-vivo, animal in-vivo, human in-vivo, and clinical pilot studies and demonstrate the unprecedented preclinical and clinical potential of LED-based photoacoustic imaging.

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Silencing of O-linked N-acetylglucosamine transferase ameliorates hypercalcemia-induced neurotoxicity in renal failure by regulating EZH2/KLF2/CXCL1 axis

Cell Death and Disease ◽

10.1038/s41419-021-04022-x ◽

2021 ◽

Vol 12 (9) ◽

Author(s):

Yaochen Cao ◽

Xin Chen ◽

Hongming Sun

Keyword(s):

Renal Failure ◽

Nerve Injury ◽

Kidney Tissue ◽

Adenovirus Vector ◽

Primary Neurons ◽

Key Factors ◽

Bioinformatics Analyses ◽

In Vivo Experiments ◽

Acetylglucosamine Transferase

AbstractHypocalcemia, associated with Calcium neurotoxicity, has been reported to induce nerve dysfunction, which is a significant problem of renal failure. This study identifies a molecular mechanism of the O-linked N-acetylglucosamine transferase (OGT)-mediated enhancer of zeste homolog 2 (EZH2)/krüppel-like factor 2 (KLF2)/chemokine (C-X-C motif) ligand 1 (CXCL1) axis underlying the hypercalcemia-induced nerve injury in renal failure. Bioinformatics analyses were used to screen out the key factors in hypercalcemia-induced nerve injury in renal failure. Chronic kidney disease (CKD) was induced by an adenine diet in mice, followed by injection of adenovirus vector carrying short hairpin RNA targeting OGT, followed by behavioral tests and collection of the cerebral cortex for primary neurons. Calcium level in neurons was measured by Fluo-4-am and Perkin Elmer+ Operetta. Neuronal apoptosis and viability were detected by flow cytometry and the MTS method. The binding of EZH2 to KLF2 promoter was verified by chromatin immunoprecipitation assay. The concentration of Ca2+ in brain tissues of CKD model mice was increased, and nerve functions were obviously damaged. High expression of OGT occurred in kidney tissue of CKD model mice. Silencing OGT reduced the hypercalcemia-induced toxicity of neurons by inhibiting the expression of EZH2, which elevated the expression of CXCL1 in primary neurons by diminishing KLF2. Silencing OGT attenuated hypercalcemia-induced neurotoxicity by regulating the EZH2/KLF2/CXCL1 axis. In vivo experiments further confirmed that silencing OGT could reduce hypercalcemia-induced nerve injury in CKD mice. Taken together, silencing OGT downregulates EZH2, which increases the expression of KLF2 and then decreases the expression of CXCL1, thus alleviating hypercalcemia-induced nerve injury in renal failure.

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Antioxidant and Hypolipidemic Activity of the Hydroethanolic Extract ofCuratella americanaL. Leaves

Oxidative Medicine and Cellular Longevity ◽

10.1155/2016/9681425 ◽

2016 ◽

Vol 2016 ◽

pp. 1-6 ◽

Cited By ~ 7

Author(s):

Rafael Henrique Oliveira Lopes ◽

Luis Fernando Benitez Macorini ◽

Katia Ávila Antunes ◽

Priscilla Pereira de Toledo Espindola ◽

Tamaeh Monteiro Alfredo ◽

...

Keyword(s):

Antioxidant Activity ◽

The Body ◽

Hypolipidemic Activity ◽

Key Factors ◽

High Fructose ◽

Scavenging Capacity ◽

Dpph Scavenging ◽

Hydroethanolic Extract ◽

Positive Controls

High levels of reactive oxygen species in the body and hyperlipidemia are key factors for the development of cardiovascular diseases such as atherosclerosis. The present study investigated the antioxidant and hypolipidemic activity of hydroethanolic extract ofCuratella americanaL. leaves (ExC). The antioxidant activity of ExC was assessed by 2,2-diphenyl-1-picrylhydrazyl free radical (DPPH) scavenging capacity and protection against hemolysis induced by 2,2′-azobis(2-amidinopropane) dihydrochloride (AAPH), followed by quantification of malondialdehyde (MDA). Wistar rats with hyperlipidemia induced by high-fructose diet (60%) were treated for 60 days with water, simvastatin (30 mg·Kg−1), ciprofibrate (2 mg·Kg−1), and ExC (200 mg·Kg−1). ExC revealed IC50of6.0±0.5 μg·mL−1, an intermediary value among positive controls used in the assay of DPPH scavenging capacity. At all concentrations (50 to 125 μg·mL−1) and times (60 to 240 min) evaluated, ExC protected erythrocytes against AAPH-induced hemolysis, which was confirmed by lower MDA levels.In vivotests showed a reduction of 34 and 45%, respectively, in serum concentration of cholesterol and triglycerides in hyperlipidemic rats treated with ExC, a similar effect compared to the reference drugs, simvastatin and ciprofibrate, respectively. Together, the results showed the antioxidant activity of ExC and its ability to improve the serum lipid profile in hyperlipidemic rats.

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In vivo tumor targeting and radionuclide imaging with self-assembled nanoparticles: Mechanisms, key factors, and their implications

Biomaterials ◽

10.1016/j.biomaterials.2006.10.002 ◽

2007 ◽

Vol 28 (6) ◽

pp. 1236-1247 ◽

Cited By ~ 90

Author(s):

Yong Woo Cho ◽

Soo Ah Park ◽

Tae Hee Han ◽

Dai Hyun Son ◽

Ji Sun Park ◽

...

Keyword(s):

Radionuclide Imaging ◽

Tumor Targeting ◽

Key Factors ◽

Self Assembled

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Deoxyribonucleic acid and polyamine synthesis in rat ventral prostate. Effects of age of the intact rat and androgen stimulation of the castrated rat with testosterone, 5α-dihydrotestosterone and 5α-androstane-3β, 17β-diol

Biochemical Journal ◽

10.1042/bj1620087 ◽

1977 ◽

Vol 162 (1) ◽

pp. 87-97 ◽

Cited By ~ 22

Author(s):

E E K Takyi ◽

D J M Fuller ◽

L J Donaldson ◽

G H Thomas

Keyword(s):

Ornithine Decarboxylase ◽

Ventral Prostate ◽

Molar Ratio ◽

Synthetic Activity ◽

Decarboxylase Activity ◽

Polyamine Synthesis ◽

Molar Ratios ◽

Ornithine Decarboxylase Activity ◽

The Relationship

The relationship between polyamine synthesis, growth and secretion in vivo was examined in ventral prostates from: (a) intact rats aged 3-60 weeks; (b) animals castrated for 7 days before injection with 5 alpha-dihydrotestosterone (17 beta-hydroxy-5-alpha-androstan-3-one), testosterone and 5 alpha-androstane-3 beta, 17 beta-diol for up to 10 days; (c) rats injected with the 3 beta, 17 beta-diol immediately after castration. Ornithine decarboxylase activity and the concentrations of putrescine, spermidine and spermine were measured. DNA-synthetic activity was monitored by measuring [125I]iododoxyuridine incorporation. An enhanced spermidine/spermine molar ratio reflected increased activity of the prostate. The ratio was higher (greater than 2) in prostates from sexually immature animals, than in the intact adult (1.5), suggesting that the ratio was indicative of the proliferative activity of the tissue. However, in the androgen-stimulated castrated rat, enhanced spermidine/spermine ratios tended to correlate with hypertrophy and secretion. In both sets of experiments there was a linear relationship between protein and spermidine content. High spermidine/spermine molar ratios were the consequence of a relatively low rate of accumulation of spermine relative to spermidine and protein. The relationship between polyamine synthesis and DNA-synthetic activity was investigated in cultured prostate. A combination of insulin (3 mug/ml) and testosterone (0.1 muM caused a stimulatory response in the incorporation of [125I]iododeoxyuridine and in cell division, despite a depleted polyamine content and low ornithine decarboxylase activity in the cultured tissue.

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