Potential roles of heparanase in cancer therapy: Current trends and future direction.

Heparanase (HPSE; heparanase-1) is an endo-ß-glucuronidase capable of degrading the carbohydrate moiety of heparan sulfate proteoglycans, thus modulating and facilitating the remodeling of the extracellular matrix and basement membrane. HPSE activity is strongly associated with major human pathological complications, including but not limited to tumor progress and angiogenesis. Several lines of literature have shown that overexpression of HPSE leads to enhanced tumor growth and metastatic transmission, as well as poor prognosis. Gene silencing of HPSE or treatment of tumor with compounds that block HPSE activity are shown to remarkably attenuate tumor progression. Therefore, targeting HPSE is considered as a potential therapeutical strategy for the treatment of cancer. Intriguingly, recent findings disclose that heparanase-2 (HPSE-2), a close homolog of HPSE but lacking enzymatic activity, can also regulate antitumor mechanisms. Given the pleiotropic roles of HPSE, further investigation is in demand to determine the precise mechanism of regulating action of HPSE in different cancer settings. In this review, we first summarize the current understanding of HPSE, such as its structure, subcellular localization, and tissue distribution. Furthermore, we systematically review the pro- and antitumorigenic roles and mechanisms of HPSE in cancer progress. In addition, we delineate HPSE inhibitors that have entered clinical trials and their therapeutic potential.

Utilizing network pharmacological analysis to investigate the key targets and mechanisms of kaempferol against oxaliplatin-induced neurotoxicity.

This study investigated the pharmacological mechanism of kaempferol in the treatment of oxaliplatin-induced neuropathic pain by network pharmacological method and cells experiment. The kaempferol and disease target genes were obtained from several databases, including TCMSP, SwissTargetPrediction, GeneCards, and CTD. Then, the common target genes of drugs and diseases were obtained using Venny online tools. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional analyses were carried out to obtain the enriched molecular pathways associated with the kaempferol and disease. Finally, we constructed a neuropathic pain cell experiment to confirm the findings. 138 intersection targets were identified between targets of kaempferol and oxaliplatin-induced neurotoxicity. Enrichment analyses revealed that the IL-17 signaling pathway was associated with the therapeutic effects of kaempferol. Kaempferol down-regulated the mRNA expression levels of TNF-α, IL-6, and CCL2 in oxaliplatin-treated astrocytes. Our findings showed that kaempferol alleviated oxaliplatin-induced neurotoxicity via regulation of inflammation-related genes.

Heterogeneous public preferences for controlling agricultural non-point source pollution based on a choice experiment.

The public's stated value and heterogeneous preferences are crucial for formulating policies and financing approaches to promote the control of agricultural non-point-source pollution (ANSP). This study aims to investigate urban residents' willingness to pay (WTP) for ANSP control and analyse the source of preference heterogeneity using a choice experiment method. Survey data were obtained from face-to-face interviews with 595 respondents in south Shaanxi Province, China. We found that respondents' average WTP for the attributes of ANSP control schemes were 2.34 yuan ($0.36) and 5.42 yuan ($0.83) per year per household for a 1% reduction in fertiliser and pesticide use, respectively. We also found significant impacts of WTP from individuals' socio-economic characteristics (i.e., gender, age, education, and income) and cognitive factors (i.e., policy understanding, and government trust). Thus, to improve the efficiency and universality of ANSP control policy, the public's willingness and preference heterogeneity should be thoroughly taken into policy formulation.

Bioinformatics analysis of C3 and CXCR4 demonstrates their potential as prognostic biomarkers in clear cell renal cell carcinoma (ccRCC).

BACKGROUND: The molecular prognostic biomarkers of clear cell renal cell carcinoma (ccRCC) are still unknown. We aimed at researching the candidate biomarkers and potential therapeutic targets of ccRCC. METHODS: Three ccRCC expression microarray datasets (include GSE14762, GSE66270 and GSE53757) were downloaded from the gene expression omnibus (GEO) database. The differentially expressed genes (DEGs) between ccRCC and normal tissues were explored. The potential functions of identified DEGs were analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). And then the protein - protein interaction network (PPI) was established to screen the hub genes. After that, the expressions of hub genes were identified by the oncomine database. The hub genes' prognostic values of patients with ccRCC were analyzed by GEPIA database. RESULTS: A total of 137 DEGs were identified by utilizing the limma package and RRA method, including 63 upregulated genes and 74 downregulated genes. It is found that 137 DEGs were mainly enriched in 82 functional terms and 24 pathways in accordance with the research results. Thirteen highest-scoring genes were screened as hub genes (include 10 upregulated genes and 3 downregulated candidate genes) by utilizing the PPI network and module analysis. Through integrating the oncoming database and GEPIA database, the author found that C3 and CXCR4 are not only overexpressed in ccRCC, but also associated with the prognosis of ccRCC. Further results could reveal that patients with high C3 expression had a poor overall survival (OS), while patients with high CTSS and TLR3 expressions had a good OS; patients with high C3 and CXCR4 expressions had a poor disease-free survival (DFS), while ccRCC patients with high TLR3 expression had a good DFS. CONCLUSION: These findings suggested that C3 and CXCR4 were the candidate biomarkers and potential therapeutic targets of ccRCC patients.

Bufadienolides from the Eggs of the Toad Bufo bufo gargarizans and Their Antimelanoma Activities.

Toads produce potent toxins, named bufadienolides, to defend against their predators. Pharmacological research has revealed that bufadienolides are potential anticancer drugs. In this research, we reported nine bufadienolides from the eggs of the toad Bufo bufo gargarizans, including two new compounds (1 and 3). The chemical structures of 1 and 3, as well as of one previously reported semisynthesized compound (2), were elucidated on the basis of extensive spectroscopic data interpretation, chemical methods, and X-ray diffraction analysis. Compound 1 is an unusual 19-norbufadienolide with rearranged A/B rings. A biological test revealed that compounds 2 and 4-8 showed potent cytotoxic activities toward human melanoma cell line SK-MEL-1 with IC50 values less than 1.0 µM. A preliminary mechanism investigation revealed that the most potent compound, 8, could induce apoptosis via PARP cleavage, while 5 and 6 significantly suppressed angiogenesis in zebrafish. Furthermore, an in vivo biological study showed that 5, 6, and 8 inhibit SK-MEL-1 cell growth significantly.

Clinical outcome of laparoscopic versus robot-assisted radical cystectomy for patients with bladder cancer: a retrospective study.

BACKGROUND: With the development of minimally invasive surgery technology, patients with bladder cancer are increasingly receiving laparoscopic radical cystectomy (LRC) or robotic-assisted radical cystectomy (RARC) treatment. The main purpose of this study was to compare the long-term outcomes of bladder cancer patients treated with LRC versus RARC. METHODS: A retrospective study to identify patients with clinical stage Ta/T1/Tis to T3 bladder cancer who underwent RARC or LRC has been performed. The perioperative outcome, recurrence, and overall survival (OS) of the two surgical methods were compared. RESULTS: 218 patients were identified from March 2010 to December 2019 in our department, which including 82 (38%) patients who received LRC and 136 (62%) patients who received RARC. There was no significant difference between the two groups in terms of lymph node collection, lymph node positive rate, resection margin positive rate, and postoperative pathological staging. Compared with the LRC group, patients in the RARC group had a median estimated blood loss (180 vs. 250 ml; P = 0.02) and reduced complications at 90 days postoperatively (30.8% vs. 46.3%; P = 0.01). Recurrence, all-cause death, and cancer-specific death occurred in 77 (35%), 55 (25%), and 39 (18%) patients, respectively. The 5-year OS rate was 54.63% and 54.65% in the RARC and LRC group (P > 0.05). The 5-year cancer-specific survival (CSS) rate was 73.32% and 61.55% in RARC and LRC group (P > 0.05). There was no significant difference in OS [hazard ratio (HR) 1.083, 95% confidence interval (CI) 0.626-1.874; P = 0.78], and CSS (HR 0.789, 95%CI 0.411-1.515; P = 0.61) between two groups. CONCLUSIONS: Both RARC and LRC were safe and effective with a similar long-term clinical outcomes. Moreover, RARC had significantly lower median estimated blood loss and reduced postoperative complications.

microRNA-148a-3p in extracellular vesicles derived from bone marrow mesenchymal stem cells suppresses SMURF1 to prevent osteonecrosis of femoral head.

Extracellular vesicle (EV)-associated microRNAs (miRNAs) have been found as the important biomarkers participating in the development of osteonecrosis of the femoral head (ONFH). Consequently, this study sought to examine the underlying mechanism of bone marrow mesenchymal stem cell (BMSC)-derived EVs containing miR-148a-3p in ONFH. The ONFH rat models were established. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) and Western blot analysis were applied to detect miR-148a-3p, Smad ubiquitination regulatory factor 1 (SMURF1), SMAD7 and B-cell CLL/lymphoma 2 (BCL2) expression, followed by determination of relationship between miR-148a-3p and SMURF1. BMSCs were isolated from normal rats and ONFH rats, and EVs were extracted from BMSCs of normal rats. BMSCs from ONFH rats were treated with mimic, inhibitor, small interfering RNA or EVs from miR-148a-3p mimic-treated BMSCs from normal rats (BMSC-EV-miR-148a-3p mimic). Cell Counting Kit-8 and alizarin red staining were utilized to detect cell viability and osteogenic differentiation of BMSCs. ONFH rats were injected with BMSC-EV-miR-148a-3p mimic to explore the function of BMSC-EV-delivered miR-148a-3p in vivo. miR-148a-3p was down-regulated in BMSCs and EVs from ONFH rats following decreased BMSCs viability and osteogenic differentiation. SMURF1 was a target gene of miR-148a-3p, and resulted in ubiquitination and degradation of SMAD7 to decreased BCL2 expression. The proliferation and differentiation of BMSCs were promoted by BMSC-EV-miR-148a-3p mimic or SMURF1 silencing. Additionally, BMSC-EV-miR-148a-3p mimic increased cell proliferation and osteogenic response, diminished SMURF1 expression, and elevated SMAD7 and BCL2 expression in ONFH rats. Collectively, miR-148a-3p overexpressed in BMSC-EVs promoted SMAD7 and BCL2 expression by inhibiting SMURF1, thus alleviating ONFH.

Induced pluripotent stem cells attenuate chronic allogeneic vasculopathy in an integrin beta-1-dependent manner.

This study aimed to determine the mechanism of isogeneic-induced pluripotent stem cells (iPSCs) homing to vascular transplants and their therapeutic effect on chronic allogeneic vasculopathy. We found that integrin ß1 (Intgß1) was the dominant integrin ß unit in iPSCs that mediates the adhesion of circulatory and endothelial cells (ECs). Intgß1 knockout or Intgß1-siRNAs inhibit iPSC adhesion and migration across activated endothelial monolayers. The therapeutic effects of the following were examined: iPSCs, Intgß1-knockout iPSCs, iPSCs transfected with Intgß1-siRNAs or nontargeting siRNAs, iPSC-derived ECs, iPSC-derived ECs simultaneously overexpressing Intgα4 and Intgß1, iPSCs precultured in endothelial medium for 3 days (endothelial-prone stem cells), primary aortic ECs, mouse embryonic fibroblasts, and phosphate-buffered saline (control). The cells were administered every 3 days for a period of 8 weeks. iPSCs, iPSCs transfected with nontargeting siRNAs, and endothelial-prone stem cells selectively homed on the luminal surface of the allografts, differentiated into ECs, and decreased neointimal proliferation. Through a single administration, we found that iPSCs trafficked to allograft lesions, differentiated into ECs within 1 week, and survived for 4-8 weeks. The therapeutic effect of a single administration was moderate. Thus, Intgß1 and pluripotency are essential for iPSCs to treat allogeneic vasculopathy.

Hydrophobic-Driven Electrochemiluminescence Enhancement via Target-Induced Self-Enrichment for Ultrasensitive Bioassay.

Considering the central challenge of the simple and efficient strategy to generate sensitive analysis technology, herein, we proposed a novel electrochemiluminescence (ECL) strategy based on target-induced self-enrichment via hydrophobic interaction to generate significant ECL enhancement for untrasensitive detection of clinical biomarkers with cardiac troponin I (cTnI) for early diagnosis of acute myocardial infarction (AMI) as a model. Typically, the first antibody of cTnI (fAb) was immobilized onto the as-prepared electrode surface with the titanium dioxide nanoflower and gold nanoclusters When there was target cTnI, it could be captured onto the electrode surface based on the specific antigen-antibody interaction to furtherly capture cholesterol-modified second antibody of cTnI to increase the hydrophobicity of the electrode surface, which could be employed for the self-enrichment of hydrophobic ECL luminophore, tris(2,2'-bipyridyl-4,4'-dicarboxylato) ruthenium(II), and coreactant, tripropylamine in the detection solution. Thus, an increased ECL emission could be achieved due to the increased concentration of ECL luminophore and coreactant, which was quantitatively related with the concentration of target cTnI. As expected, a higher sensitivity was obtained with a detection limit of 0.04 pg/mL based on simplest operations of the proposed strategy with target-induced self-enrichment via hydrophobic interaction. Importantly, this hydrophobic interaction-based ECL strategy could be easily expanded to the bioassay of various biomarkers, providing an efficient tool for early clinical diagnosis of AMI and some other diseases.

Polyploidy promotes species diversification of Allium through ecological shifts.

Despite the role of polyploidy in multiple evolutionary processes, its impact on plant diversification remains controversial. An increased polyploid frequency may facilitate speciation through shifts in ecology, morphology or both. Here we used Allium to evaluate: (1) the relationship between intraspecific polyploid frequency and species diversification rate; and (2) whether this process is associated with habitat and/or trait shifts. Using eight plastid and nuclear ribosomal markers, we built a phylogeny of 448 Allium species, representing 46% of the total. We quantified intraspecific ploidy diversity, heterogeneity in diversification rates and their relationship along the phylogeny using trait-dependent diversification models. Finally, we evaluated the association between polyploidisation and habitat or trait shifts. We detected high ploidy diversity in Allium and a polyploidy-related diversification rate shift with a probability of 95% in East Asia. Allium lineages with high polyploid frequencies had higher species diversification rates than those of diploids or lineages with lower polyploid frequencies. Shifts in speciation rates were strongly correlated with habitat shifts linked to particular soil conditions; 81.7% of edaphic variation could be explained by polyploidisation. Our study emphasises the role of intraspecific polyploid frequency combined with ecological drivers on Allium diversification, which may explain plant radiations more generally.

An off/on thrombin activated energy driven molecular machine for sensitive detection of human thrombin via non-enzymatic catalyst recycling amplification.

In this article, we report a novel dual on/off thrombin fluorescence aptasensor by combining the energy driven target induced strand displacement reaction and a non-enzyme catalyst recycling DNA machine. Firstly, the specific binding of an aptamer strand and thrombin induce the release of a catalyst which was used as a DNA machine trigger. Subsequently, the catalyst as the trigger initiated the DNA machine through nucleic acid hybridization and branch migration of the DNA machine, resulting in the DNA substrate melting and re-hybridization. In such a working model, the DNA machine achieved cooperative control of the circular strand displacement reaction, realizing catalyst recycling and dual-amplification. The fluorescence signal change of FAM and ROX accumulation had a good linear relationship with the thrombin concentration in the range of 1 fM to 1 nM. On account of catalyst recycling and dual recognition, the detection limit for thrombin was determined to be as low as 0.45 fM (S/N = 3).This biosensor also showed good selectivity for thrombin without being affected by some other proteins, such as PSA, lysozyme etc. Moreover, this assay can be applied to the detection of thrombin in diluted human serum.

Posttranslational regulation of PGC-1α and its implication in cancer metabolism.

Deregulation of cellular metabolism is well established in cancer. The mitochondria are dynamic organelles and act as the center stage for energy metabolism. Central to mitochondrial regulatory network is peroxisome proliferator-activated receptor γ coactivator 1a (PGC-1α), which serves as a master regulator of mitochondrial proliferation and metabolism. The activity and stability of PGC-1α are subject to dynamic and versatile posttranslational modifications including phosphorylation, ubiquitination, methylation and acetylation in response to metabolic stress and other environmental signals. In this review, we describe the structure of PGC-1α. Then, we discuss recent advances in the posttranslational regulatory machinery of PGC-1α, which affects its transcriptional activity, stability and organelle localization. Furthermore, we address the important roles of PGC-1α in tumorigenesis and malignancy. Finally, we also mention the clinical therapeutic potentials of PGC-1α modulators. A better understanding of the elegant function of PGC-1α in cancer progression could provide novel insights into therapeutic interventions through the targeting of PGC-1α signaling.

Impact of IL-22 and IL-22 receptor alpha 1 polymorphisms on preeclampsia risk in Chinese Han women.

Previous studies have indicated that an increased inflammatory response plays an important role in preeclampsia (PE), and rising levels of interleukin (IL)-22 can trigger inflammation and hyperproliferation, leading to increased production of several pro-inflammatory cytokines such as IL-1, IL-6, and IL-8. We aimed to investigate the association between polymorphisms of IL-22 and IL-22 receptor alpha 1 gene (IL-22RA1) and PE in Chinese Han population. Single nucleotide polymorphisms (SNPs) rs2227485 in IL-22 and rs3795299 in IL-22RA were genotyped by Taqman real-time PCR in 1071 PE patients and 1263 control subjects. Differences in genetic distribution were compared between two groups using the chi-square test. Significant differences were observed in genotypic and allelic frequencies of IL-22RA1 rs3795299 between healthy controls and PE patients (P < 0.001 by genotype; P = 0.001, odds ratio = 1.253, 95% confidence interval 1.103-1.424 by allele). There were also significant differences in genotypic and allelic frequencies of rs3795299 between late-onset/mild PE and control groups. In addition, we found obvious statistic difference for the allele of early-onset PE/the genotype of late-onset PE and control subgroups for IL-22 rs2227485. IL-22 rs2227485 and IL-22RA1 rs3795299 may be associated with the development of PE in Chinese Han population. However, further validation is required in other populations, as well as an evaluation of the association of other SNPs in IL-22 and IL-22RA1 with PE.

MicroRNAs as potential biomarkers for the diagnosis of glioma: A systematic review and meta-analysis.

Glioma is the most common central nervous system tumor and associated with poor prognosis. Identifying effective diagnostic biomarkers for glioma is particularly important in order to guide optimizing treatment. MicroRNAs (miRNAs) have drawn much attention because of their diagnostic value in diverse cancers, including glioma. We summarized studies to identify the potential diagnostic values of miRNAs in glioma patients. We included articles reporting miRNAs for differentiation of glioma patients from controls. We calculated sensitivities, specificities, and area under the curves (AUC) of individual miRNA and miRNA panels. We found that overall sensitivity, specificity, and AUC of miRNAs in diagnosis of glioma were 85% (95% confidence interval [CI]: 0.81-0.89), 90% (95% CI 0.85-0.93), and 93% (95% CI 0.91-0.95), respectively. Meta-regression analysis showed that the detection of miRNAs expression in cerebrospinal fluid (CSF) and brain tissue largely improved the diagnostic accuracy. Likewise, panels of multiple miRNAs could enhance the pooled sensitivity. Moreover, AUC of miR-21 was 0.88, with 86% sensitivity and 94% specificity. This study demonstrated that miRNAs could function as potential diagnosis markers in glioma. Detection of miRNAs in CSF and brain tissue displays high accuracy in the diagnosis of glioma.

Galactose-Functionalized Double-Hydrophilic Block Glycopolymers and Their Thermoresponsive Self-Assembly Dynamics.

Glycopolymers with large galactose units are attractive in biological processes because of their ability to selectively recognize lectin proteins. Recently, thermoresponsive double-hydrophilic block glycopolymers (TDHBGs) have been designed, which allow sugar residues to expose or hide via the lower critical solution temperature (LCST)-type phase transition. In this work, we first synthesize a new type of TDHBGs, composed of a thermoresponsive poly(di(ethylene glycol)methyl ether methacrylate) block and a galactose-functionalized, poly(6- O-vinyladipoyl-d-galactose) (POVNG) block. The LCST can be tuned by varying the size of the POVNG block. Then, we have systematically investigated their thermoresponsive self-assembly behavior, using static and dynamic light scattering techniques, combined with transmission electron microscopy (TEM) imaging. It is found that the TDHBGs possess both micellization and LCST-type transition, and there exist strong interactions between them, depending on the concentration and structure of the TDHBGs. It is particularly interesting that for the same type of TDHBGs under different conditions, such interactions result in rich morphologies of the formed micelles (or nanoparticles) such as spheres, hollow spheres, prolate ellipsoids, crystal-like, and so on, thus potentially enriching their biological applications by noting that they are hepatoma-targeting glycopolymers.

Assembly of g-C3N4-based type II and Z-scheme heterojunction anodes with improved charge separation for photoelectrojunction water oxidation.

Graphitic carbon nitride (g-C3N4) has been widely studied as a metal-free photocatalyst, leading to some excellent results; however, the rapid recombination of photogenerated charge carriers substantially limits its performance. Here, we establish two types of g-C3N4-based heterojunction (type II and nonmediator assisted Z-scheme) photoanodes on a transparent conducting substrate via coupling with rod-like and nanoparticulate WO3, respectively. In these composites, g-C3N4 film grown by electrophoretic deposition of exfoliated g-C3N4 serves as the host or guest material. The optimized type II WO3/g-C3N4 composite exhibits an enhanced photocurrent of 0.82 mA cm-2 at 1.23 V vs. RHE and an incident photo-to-current conversion efficiency (IPCE) of 33% as compared with pure WO3 nanorods (0.22 mA cm-2 for photocurrent and 15% for IPCE). Relative to pure g-C3N4 film (with a photocurrent of several microampere and an IPCE of 2%), a largely improved photocurrent of 0.22 mA cm-2 and an IPCE of 20% were acquired for the Z-scheme g-C3N4/WO3 composite. The enhancement can be attributed to accelerated charge separation in the heterointerface because of the suitably aligned band gap between WO3 and g-C3N4, as confirmed by optical spectroscopy and ultraviolet photoelectron spectroscopy (UPS) analysis. The photocatalytic process and mechanism of the g-C3N4-based heterojunctions are proposed herein, which potentially explain the origin of the enhanced photoelectrochemical performance. This achievement and the fundamental information supplied here indicate the importance of rationally designing heterojunction photoelectrodes to improve the performance of semiconductors. This is particularly important for materials such as pure g-C3N4 and WO3, as their photoactivities are strongly restricted by high recombination rates.

Musashi2 modulates K562 leukemic cell proliferation and apoptosis involving the MAPK pathway.

The RNA-binding protein Musashi2 (Msi2) has been identified as a master regulator within a variety of stem cell populations via the regulation of translational gene expression. A recent study has suggested that Msi2 is strongly expressed in leukemic cells of acute myeloid leukemia patients, and elevated Msi2 is associated with poor prognosis. However, the potential role of Msi2 in leukemogenesis is still not well understood. Here, we investigated the effect of Msi2 knockdown on the biological properties of leukemic cells. High expression of Msi2 was found in K562 and KG-1a leukemic cell lines, and low expression was observed in the U937 cell line. We transduced K562 cells with two independent adenoviral shRNA vectors targeting Msi2 and confirmed knockdown of Msi2 at the mRNA and protein levels. Msi2 silencing inhibited cell growth and caused cell cycle arrest by increasing the expression of p21 and decreasing the expression of cyclin D1 and cdk2. In addition, knockdown of Msi2 promoted cellular apoptosis via the upregulation of Bax and downregulation of Bcl-2 expression. Furthermore, Msi2 knockdown resulted in the inactivation of the ERK/MAPK and p38/MAPK pathways, but no remarkable change in p-AKT was observed. These data provide evidence that Msi2 plays an important role in leukemogenesis involving the MAPK signaling pathway, which indicates that Msi2 may be a novel target for leukemia treatment.

Quantitative detection of circulating nucleophosmin mutations DNA in the plasma of patients with acute myeloid leukemia.

OBJECTIVE: The aim of this study was to quantify the copies of circulating nucleophosmin (NPM) mutations DNA in the plasma of patients with acute myeloid leukemia (AML) and to explore the association of circulating NPM mutation levels with clinical characteristics. DESIGN AND METHODS: The presence of NPM mutations in 100 Chinese patients newly diagnosed with AML were identified by RT-PCR and sequencing analysis. Copies of circulating NPM mutation A (NPM mut.A) DNA in the plasma of mutation-positive cases were quantified by real-time quantitative PCR (qRT-PCR). Furthermore, the association of circulating NPM mutation levels and clinical characteristics was analyzed. RESULTS: NPM mutations were identified in 37 of the 100 patients and all cases were NPM mut.A. The circulating NPM mut.A levels ranged from 0.35×10(8) copies/ml to 6.0×10(8) copies/ml in the 37 mutation-positive cases. The medium and quartile M (P25, P75) of the circulating NPM mut.A levels in patients classified as M2, M4 and M5 morphological subtypes were 1.35×10(8) (0.76×10(8), 1.91×10(8)) copies/ml, 1.81×10(8) (1.47×10(8), 2.2×10(8)) copies/ml and 2.50×10(8) (2.42×10(8), 3.05×10(8)) copies/ml, respectively. Circulating NPM mut.A levels were significantly higher in patients with the M5 subtype of AML compared to patients with the M2 and M4 subtypes (p=0.000, p=0.046). In addition, circulating NPM mut.A copies were significantly associated with a higher white blood cell count, platelet count and bone marrow blast percentage (p<0.05). CONCLUSION: Our results suggest that circulating NPM mutations DNA assay serves as a complementary to the routine investigative protocol of NPM-mutated leukemia.

A novel self-assembling peptide with UV-responsive properties.

A novel heptapeptide comprising Ile-Gln-Ser-Pro-His-Phe-Phe (IQSPHFF) identified and found to undergo self-assembly into microparticles in solution. To understand the effects of ultraviolet (UV) irradiation on the self-assembly process, IQSPHFF solutions were exposed to the UV light of 365 nm at room temperature. This exposure was found to have a profound effect on the morphology of the self-assembled aggregates, converting the microparticles to nanorod shapes. Circular dichroism and FTIR studies indicated distinct structural differences in the arrangements of the peptide moieties before and after UV irradiation. However, Mass spectrum analysis and high performance liquid chromatography of the peptide molecules before and after UV irradiation demonstrated that the chemical structure of IQSPHFF was not changed. UV-visible spectroscopy and fluorescence spectroscopy studies showed that the absorption peak both increased after UV irradiation. Overall, our data show that the heptapeptide with UV-responsive properties.

Inhibition of Ferroptosis by Mesenchymal Stem Cell-Derived Exosomes in Acute Spinal Cord Injury: Role of Nrf2/GCH1/BH4 Axis.

OBJECTIVE: The therapeutic benefits of exosomes obtained from mesenchymal stem cells (MSCs) in acute spinal cord injury (SCI) have been demonstrated in recent years, but the precise mechanisms remain unknown. In this study, the efficacy and mechanisms of MSC-derived exosomes (MSC-Exo) in acute SCI were investigated. METHODS: By utilizing a BV2 ferroptosis cellular model and an SCI rat model, we investigated the effects of MSC-Exo on iron death related indicators and NF-E2 related factor 2 (Nrf2)/GTP cyclolase I (GCH1)/5,6,7,8-tetrahydrobiopterin (BH4) signaling axis, as well as their therapeutic effects on SCI rats. RESULTS: The results revealed that MSC-Exo effectively inhibited the production of ferrous iron, lipid peroxidation products malonaldehyde and reactive oxygen species, and ferroptosis-promoting factor prostaglandin-endoperoxide synthase 2. Concurrently, they upregulated ferroptosis suppressors FTH-1 (ferritin heavy chain 1), SLC7A11 (solute carrier family 7 member 11), FSP1 (ferroptosis suppressor protein 1), and GPX4 (glutathione peroxidase 4), contributing to enhanced neurological recovery in SCI rats. Further analysis showed the Nrf2/GTP/BH4 signaling pathway's critical role in suppressing ferroptosis. Additionally, MSC-Exo was found to inhibit lipopolysaccharide-induced ferroptosis in BV2 cells and SCI rats by activating the Nrf2/GCH1/BH4 axis. CONCLUSION: In summary, the study demonstrates that MSC-Exo mitigates microglial cell ferroptosis via the Nrf2/GCH1/BH4 axis, showing potential for preserving and restoring neurological function post-SCI.