Research Progress of SN38 Drug Delivery System in Cancer Treatment.

The active metabolite of irinotecan (CPT-11), 7-ethyl-10-hydroxycamptothecin (SN38), is 100-1000 times more active than CPT-11 and has shown inhibitory effects on a range of cancer cells, including those from the rectal, small cell lung, breast, esophageal, uterine, and ovarian malignancies. Despite SN38's potent anticancer properties, its hydrophobicity and pH instability have caused substantial side effects and anticancer activity loss, which make it difficult to use in clinical settings. To solve the above problems, the construction of SN38-based drug delivery systems is one of the most feasible methods to improve drug solubility, enhance drug stability, increase drug targeting ability, improve drug bioavailability, enhance therapeutic efficacy and reduce adverse drug reactions. Therefore, based on the targeting mechanism of drug delivery systems, this paper reviews SN38 drug delivery systems, including polymeric micelles, liposomal nanoparticles, polymeric nanoparticles, protein nanoparticles, conjugated drug delivery systems targeted by aptamers and ligands, antibody-drug couplings, magnetic targeting, photosensitive targeting, redox-sensitive and multi-stimulus-responsive drug delivery systems, and co-loaded drug delivery systems. The focus of this review is on nanocarrier-based SN38 drug delivery systems. We hope to provide a reference for the clinical translation and application of novel SN38 medications.

Autopsy analysis reveals increased macrophage infiltration and cell apoptosis in COVID-19 patients with severe pulmonary fibrosis.

Clinical data indicates that SARS-CoV-2 infection-induced respiratory failure is a fatal condition for severe COVID-19 patients. However, the pathological alterations of different types of respiratory failure remained unknown for severe COVID-19 patients. This study aims to evaluate whether there are differences in the performance of various types of respiratory failure in severe COVID-19 patients and investigate the pathological basis for these differences. The lung tissue sections of severe COVID-19 patients were assessed for the degree of injury and immune responses. Transcriptome data were used to analyze the molecular basis in severe COVID-19 patients. Severe COVID-19 patients with combined oxygenation and ventilatory failure presented more severe pulmonary fibrosis, airway obstruction, and prolonged disease course. The number of M2 macrophages increased with the degree of fibrosis in patients, suggesting that it may be closely related to the development of pulmonary fibrosis. The co-existence of pro-inflammatory and anti-inflammatory cytokines in the pulmonary environment could also participate in the progression of pulmonary fibrosis. Furthermore, the increased apoptosis in the lungs of COVID-19 patients with severe pulmonary fibrosis may represent a critical factor linking sustained inflammatory responses to fibrosis. Our findings indicate that during the extended phase of COVID-19, antifibrotic and antiapoptotic treatments should be considered in conjunction with the progression of the disease.

Dynamic Dimerization of Chemokine Receptors and Potential Inhibitory Role of Their Truncated Isoforms Revealed through Combinatorial Prediction.

Chemokine receptors play crucial roles in fundamental biological processes. Their malfunction may result in many diseases, including cancer, autoimmune diseases, and HIV. The oligomerization of chemokine receptors holds significant functional implications that directly affect their signaling patterns and pharmacological responses. However, the oligomerization patterns of many chemokine receptors remain poorly understood. Furthermore, several chemokine receptors have highly truncated isoforms whose functional role is not yet clear. Here, we computationally show homo- and heterodimerization patterns of four human chemokine receptors, namely CXCR2, CXCR7, CCR2, and CCR7, along with their interaction patterns with their respective truncated isoforms. By combining the neural network-based AlphaFold2 and physics-based protein-protein docking tool ClusPro, we predicted 15 groups of complex structures and assessed the binding affinities in the context of atomistic molecular dynamics simulations. Our results are in agreement with previous experimental observations and support the dynamic and diverse nature of chemokine receptor dimerization, suggesting possible patterns of higher-order oligomerization. Additionally, we uncover the strong potential of truncated isoforms to block homo- and heterodimerization of chemokine receptors, also in a dynamic manner. Our study provides insights into the dimerization patterns of chemokine receptors and the functional significance of their truncated isoforms.

Positioning SUMO as an immunological facilitator of oncolytic viruses for high-grade glioma.

Oncolytic viral (OV) therapies are promising novel treatment modalities for cancers refractory to conventional treatment, such as glioblastoma, within the central nervous system (CNS). Although OVs have received regulatory approval for use in the CNS, efficacy is hampered by obstacles related to delivery, under-/over-active immune responses, and the "immune-cold" nature of most CNS malignancies. SUMO, the Small Ubiquitin-like Modifier, is a family of proteins that serve as a high-level regulator of a large variety of key physiologic processes including the host immune response. The SUMO pathway has also been implicated in the pathogenesis of both wild-type viruses and CNS malignancies. As such, the intersection of OV biology with the SUMO pathway makes SUMOtherapeutics particularly interesting as adjuvant therapies for the enhancement of OV efficacy alone and in concert with other immunotherapeutic agents. Accordingly, the authors herein provide: 1) an overview of the SUMO pathway and its role in CNS malignancies; 2) describe the current state of CNS-targeted OVs; and 3) describe the interplay between the SUMO pathway and the viral lifecycle and host immune response.

CrMP-Sol database: classification, bioinformatic analyses and comparison of cancer-related membrane proteins and their water-soluble variant designs.

Membrane proteins are critical mediators for tumor progression and present enormous therapeutic potentials. Although gene profiling can identify their cancer-specific signatures, systematic correlations between protein functions and tumor-related mechanisms are still unclear. We present here the CrMP-Sol database ( https://bio-gateway.aigene.org.cn/g/CrMP ), which aims to breach the gap between the two. Machine learning was used to extract key functional descriptions for protein visualization in the 3D-space, where spatial distributions provide function-based predictive connections between proteins and cancer types. CrMP-Sol also presents QTY-enabled water-soluble designs to facilitate native membrane protein studies despite natural hydrophobicity. Five examples with varying transmembrane helices in different categories were used to demonstrate the feasibility. Native and redesigned proteins exhibited highly similar characteristics, predicted structures and binding pockets, and slightly different docking poses against known ligands, although task-specific designs are still required for proteins more susceptible to internal hydrogen bond formations. The database can accelerate therapeutic developments and biotechnological applications of cancer-related membrane proteins.

Targeted drug delivery systems for elemene in cancer therapy: The story thus far.

Elemene (ELE) is a group of broad-spectrum anticancer active ingredients with low toxicity extracted from traditional Chinese medicines (TCMs), such as Curcumae Rhizoma and Curcuma Radix, which can exert antitumour activities by regulating various signal pathways and targets. However, the strong hydrophobicity, short half-life, low bioavailability and weak in vivo targeting ability of ELE restrict its use. Targeted drug delivery systems based on nanomaterials are among the most viable methods to overcome these shortcomings. In this review, we first summarize recent studies on the clinical uses of ELE as an adjunct antitumour drug. ELE-based combination strategies have great promise for enhancing efficacy, reducing adverse reactions, and improving patients' quality of life and immune function. Second, we summarize recent studies on the antitumour mechanisms of ELE and ELE-based combination strategies. The potential mechanisms include inducing pyroptosis and ferroptosis, promoting senescence, regulating METTL3-mediated m6A modification, suppressing the Warburg effect, and inducing apoptosis and cell cycle arrest. Most importantly, we comprehensively summarize studies on the combination of targeted drug delivery systems with ELE, including passively and actively targeted drug delivery systems, stimuli-responsive drug delivery systems, and codelivery systems for ELE combined with other therapies, which have great promise in improving drug bioavailability, increasing drug targeting ability, controlling drug release, enhancing drug efficacy, reducing drug adverse effects and reversing MDR. Our summary will provide a reference for the combination of TCMs such as ELE with advanced targeted drug delivery systems in the future.

Reverse-QTY code design of active human serum albumin self-assembled amphiphilic nanoparticles for effective anti-tumor drug doxorubicin release in mice.

Human serum albumin (HSA) is a highly water-soluble protein with 67% alpha-helix content and three distinct domains (I, II, and III). HSA offers a great promise in drug delivery with enhanced permeability and retention effect. But it is hindered by protein denaturation during drug entrapment or conjugation that result in distinct cellular transport pathways and reduction of biological activities. Here we report using a protein design approach named reverse-QTY (rQTY) code to convert specific hydrophilic alpha-helices to hydrophobic to alpha-helices. The designed HSA undergo self-assembly of well-ordered nanoparticles with highly biological actives. The hydrophilic amino acids, asparagine (N), glutamine (Q), threonine (T), and tyrosine (Y) in the helical B-subdomains of HSA were systematically replaced by hydrophobic leucine (L), valine (V), and phenylalanine (F). HSArQTY nanoparticles exhibited efficient cellular internalization through the cell membrane albumin binding protein GP60, or SPARC (secreted protein, acidic and rich in cysteine)-mediated pathways. The designed HSArQTY variants displayed superior biological activities including: i) encapsulation of drug doxorubicin, ii) receptor-mediated cellular transport, iii) tumor cell targeting, and iv) antitumor efficiency compare to denatured HSA nanoparticles. HSArQTY nanoparticles provided superior tumor targeting and antitumor therapeutic effects compared to the albumin nanoparticles fabricated by antisolvent precipitation method. We believe that the rQTY code is a robust platform for specific hydrophobic modification of functional hydrophilic proteins with clear-defined binding interfaces.

Group II metabotropic glutamate receptor activation suppresses ATP currents in rat dorsal root ganglion neurons.

P2X3 receptors and group II metabotropic glutamate receptors (mGluRs) have been found to be expressed in primary sensory neurons. P2X3 receptors participate in a variety of pain processes, while the activation of mGluRs has an analgesic effect. However, it's still unclear whether there is a link between them in pain. Herein, we reported that the group II mGluR activation inhibited the electrophysiological activity of P2X3 receptors in rat dorsal root ganglia (DRG) neurons. Group II mGluR agonist LY354740 concentration-dependently decreased P2X3 receptor-mediated and α,ß-methylene-ATP (α,ß-meATP)-evoked inward currents in DRG neurons. LY354740 significantly suppressed the maximum response of P2X3 receptor to α,ß-meATP, but did not change their affinity. Inhibition of ATP currents by LY354740 was blocked by the group II mGluR antagonist LY341495, also prevented by the intracellular dialysis of either the Gi/o protein inhibitor pertussis toxin, the cAMP analog 8-Br-cAMP, or the protein kinase A (PKA) inhibitor H-89. Moreover, LY354740 decreased α,ß-meATP-induced membrane potential depolarization and action potential bursts in DRG neurons. Finally, intraplantar injection of LY354740 also relieved α,ß-meATP-induced spontaneous nociceptive behaviors and mechanical allodynia in rats by activating peripheral group Ⅱ mGluRs. These results indicated that peripheral group II mGluR activation inhibited the functional activity of P2X3 receptors via a Gi/o protein and cAMP/PKA signaling pathway in rat DRG neurons, which revealed a novel mechanism underlying analgesic effects of peripheral group II mGluRs. This article is part of the Special Issue on "Purinergic Signaling: 50 years".

Atypical Whipple's disease with special endoscopic manifestations: A case report.

BACKGROUND: Whipple's disease is a rare systemic infection caused by Tropheryma whipplei. Most patients present with nonspecific symptoms, and routine laboratory and imaging examination results also lack specificity. The diagnosis often relies on invasive manipulation, pathological examination, and molecular techniques. These difficulties in diagnosing Whipple's disease often result in misdiagnosis and inappropriate treatments. CASE SUMMARY: This paper reports on the case of a 58-year-old male patient who complained of fatigue and decreased exercise capacity. The results of routine blood tests indicated hypochromic microcytic anemia. Results of gastroscopy and capsule endoscopy showed multiple polypoid bulges distributed in the duodenal and proximal jejunum. A diagnosis of small intestinal adenomatosis was initially considered; hence, the Whipple procedure, a pylorus-preserving pancreaticoduodenectomy, was performed. Pathological manifestations showed many periodic acid-Schiff-positive macrophages aggregated in the intestinal mucosa of the duodenum, upper jejunum, and surrounding lymph nodes. Based on comprehensive analysis of symptoms, laboratory findings, and pathological manifestations, the patient was finally diagnosed with Whipple's disease. After receiving 1 mo of antibiotic treatment, the fatigue and anemia were significantly improved. CONCLUSION: This case presented with atypical gastrointestinal manifestations and small intestinal polypoid bulges, which provided new insight on the diagnosis of Whipple's disease.

Structural informatic study of determined and AlphaFold2 predicted molecular structures of 13 human solute carrier transporters and their water-soluble QTY variants.

Solute carrier transporters are integral membrane proteins, and are important for diverse cellular nutrient transports, metabolism, energy demand, and other vital biological activities. They have recently been implicated in pancreatic cancer and other cancer metastasis, angiogenesis, programmed cell death and proliferation, cell metabolism and chemo-sensitivity. Here we report the study of 13 human solute carrier membrane transporters using the highly accurate AlphaFold2 predictions of 3D protein structures. In the native structures, there are hydrophobic amino acids leucine (L), isoleucine (I), valine (V) and phenylalanine (F) in the transmembrane alpha-helices. These hydrophobic amino acids L, I, V, F are systematically replaced by hydrophilic amino acids glutamine (Q), threonine (T) and tyrosine (Y), thus the QTY code. Therefore, these QTY variant transporters become water-soluble without requiring detergents. We present the superposed structures of these native solute carrier transporters and their water-soluble QTY variants. The superposed structures show remarkable similarity with RMSD ~ 1 Å-< 3 Å despite > 46% protein sequence substitutions in transmembrane alpha-helices. We also show the differences of surface hydrophobicity between the native solute carrier transporters and their QTY variants. Our study may further stimulate designs of water-soluble transmembrane proteins and other aggregated proteins for drug discovery and biotechnological applications.

Advanced glycation end products induce senescence of atrial myocytes and increase susceptibility of atrial fibrillation in diabetic mice.

Diabetes mellitus (DM) is a common chronic metabolic disease caused by significant accumulation of advanced glycation end products (AGEs). Atrial fibrillation (AF) is a common cardiovascular complication of DM. Here, we aim to clarify the role and mechanism of atrial myocyte senescence in the susceptibility of AF in diabetes. Rapid transesophageal atrial pacing was used to monitor the susceptibility of mice to AF. Whole-cell patch-clamp was employed to record the action potential (AP) and ion channels in single HL-1 cell and mouse atrial myocytes. More importantly, anti-RAGE antibody and RAGE-siRNA AAV9 were used to investigate the relationship among diabetes, aging, and AF. The results showed that elevated levels of p16 and retinoblastoma (Rb) protein in the atrium were associated with increased susceptibility to AF in diabetic mice. Mechanistically, AGEs increased p16/Rb protein expression and the number of SA-ß-gal-positive cells, prolonged the action potential duration (APD), reduced protein levels of Cav1.2, Kv1.5, and current density of ICa,L , IKur in HL-1 cells. Anti-RAGE antibody or RAGE-siRNA AAV9 reversed these effects in vitro and in vivo, respectively. Furthermore, downregulating p16 or Rb by siRNA prevented AGEs-mediated reduction of Cav1.2 and Kv1.5 proteins expression. In conclusion, AGEs accelerated atrial electrical remodeling and cellular senescence, contributing to increased AF susceptibility by activating the p16/Rb pathway. Inhibition of RAGE or the p16/Rb pathway may be a potential therapeutic target for AF in diabetes.

Autophagy-based unconventional secretion of HMGB1 in glioblastoma promotes chemosensitivity to temozolomide through macrophage M1-like polarization.

BACKGROUND: Glioblastoma (GB) is the most common and highly malignant brain tumor characterized by aggressive growth and resistance to alkylating chemotherapy. Autophagy induction is one of the hallmark effects of anti-GB therapies with temozolomide (TMZ). However, the non-classical form of autophagy, autophagy-based unconventional secretion, also called secretory autophagy and its role in regulating the sensitivity of GB to TMZ remains unclear. There is an urgent need to illuminate the mechanism and to develop novel therapeutic targets for GB. METHODS: Cancer genome databases and paired-GB patient samples with or without TMZ treatment were used to assess the relationship between HMGB1 mRNA levels and overall patient survival. The relationship between HMGB1 protein level and TMZ sensitivity was measured by immunohistochemistry, ELISA, Western blot and qRT-PCR. GB cells were engineered to express a chimeric autophagic flux reporter protein consisting of mCherry, GFP and LC3B. The role of secretory autophagy in tumor microenvironment (TME) was analyzed by intracranial implantation of GL261 cells. Coimmunoprecipitation (Co-IP) and Western blotting were performed to test the RAGE-NFκB-NLRP3 inflammasome pathway. RESULTS: The exocytosis of HMGB1 induced by TMZ in GB is dependent on the secretory autophagy. HMGB1 contributed to M1-like polarization of tumor associated macrophages (TAMs) and enhanced the sensitivity of GB cells to TMZ. Mechanistically, RAGE acted as a receptor for HMGB1 in TAMs and through RAGE-NFκB-NLRP3 inflammasome pathway, HMGB1 enhanced M1-like polarization of TAMs. Clinically, the elevated level of HMGB1 in sera may serve as a beneficial therapeutic-predictor for GB patients under TMZ treatment. CONCLUSIONS: We demonstrated that enhanced secretory autophagy in GB facilitates M1-like polarization of TAMs to enhance TMZ sensitivity of GB cells. HMGB1 acts as a key regulator in the crosstalk between GB cells and tumor-suppressive M1-like TAMs in GB microenvironment and may be considered as an adjuvant for the chemotherapeutic agent TMZ.

Comprehensive omics analyses profile genesets related with tumor heterogeneity of multifocal glioblastomas and reveal LIF/CCL2 as biomarkers for mesenchymal subtype.

Rationale: Around 10%-20% patients with glioblastoma (GBM) are diagnosed with more than one tumor lesions or multifocal GBM (mGBM). However, the understanding on genetic, DNA methylomic, and transcriptomic characteristics of mGBM is still limited. Methods: In this study, we collected nine tumor foci from three mGBM patients followed by whole genome sequencing, whole genome bisulfite sequencing, RNA sequencing, and immunohistochemistry. The data were further examined using public GBM databases and GBM cell line. Results: Analysis on genetic data confirmed common features of GBM, including gain of chr.7 and loss of chr.10, loss of critical tumor suppressors, high frequency of PDGFA and EGFR amplification. Through profiling DNA methylome of individual tumor foci, we found that promoter methylation status of genes involved in detection of chemical stimulus, immune response, and Hippo/YAP1 pathway was significantly changed in mGBM. Although both CNV and promoter methylation alteration were involved in heterogeneity of different tumor foci from same patients, more CNV events than promoter hypomethylation events were shared by different tumor foci, implying CNV were relatively earlier than promoter methylation alteration during evolution of different tumor foci from same mGBM. Moreover, different tumor foci from same mGBM assumed different molecular subtypes and mesenchymal subtype was prevalent in mGBM, which might explain the worse prognosis of mGBM than single GBM. Interestingly, we noticed that LIF and CCL2 was tightly correlated with mesenchymal subtype tumor focus in mGBM and predicted poor survival of GBM patients. Treatment with LIF and CCL2 produced mesenchymal-like transcriptome in GBM cells. Conclusions: Together, our work herein comprehensively profiled multi-omics features of mGBM and emphasized that components of extracellular microenvironment, such as LIF and CCL2, contributed to the evolution and prognosis of tumor foci in mGBM patients.

Comparing 2 crystal structures and 12 AlphaFold2-predicted human membrane glucose transporters and their water-soluble glutamine, threonine and tyrosine variants.

Membrane transporters including glucose transporters (GLUTs) are involved in cellular energy supplies, cell metabolism and other vital biological activities. They have also been implicated in cancer proliferation and metastasis, thus they represent an important target in combatting cancer. However, membrane transporters are very difficult to study due to their multispan transmembrane properties. The new computational tool, AlphaFold2, offers highly accurate predictions of three-dimensional protein structures. The glutamine, threonine and tyrosine (QTY) code provides a systematic method of rendering hydrophobic sequences into hydrophilic ones. Here, we present computational studies of native integral membrane GLUTs with 12 transmembrane helical segments determined by X-ray crystallography and CryoEM, comparing the AlphaFold2-predicted native structure to their water-soluble QTY variants predicted by AlphaFold2. In the native structures of the transmembrane helices, there are hydrophobic amino acids leucine (L), isoleucine (I), valine (V) and phenylalanine (F). Applying the QTY code, these hydrophobic amino acids are systematically replaced by hydrophilic amino acids, glutamine (Q), threonine (T) and tyrosine (Y) rendering them water-soluble. We present the superposed structures of native GLUTs and their water-soluble QTY variants. The superposed structures show remarkable similar residue mean square distance values between 0.47 and 3.6 Å (most about 1-2 Å) despite >44% transmembrane amino acid differences. We also show the differences of hydrophobicity patches between the native membrane transporters and their QTY variants. We explain the rationale why the membrane protein QTY variants become water-soluble. Our study provides insight into the differences between the hydrophobic helices and hydrophilic helices, and offers confirmation of the QTY method for studying multispan transmembrane proteins and other aggregated proteins through their water-soluble variants.

[Predictive Value of Newly Diagnosed IgG Level in Patients with IgG-type Multiple Myeloma after Initial Treatment].

OBJECTIVE: To explore the predictive value of newly diagnosed IgG levels in the recurrence of IgG-type multiple myeloma (MM) patients after initial treatment. METHODS: The clinical and pathological data of 91 patients newly diagnosed IgG-type MM who were hospitalized in the Department of Hematology of the Second People's Hospital of Yichang and Department of Oncology of The Affiliated Hospital of Jianghan University from April 2010 to March 2019 were collected. According to the median IgG level at the time of initial diagnosis, patients were divided into high IgG group and low IgG group. The recurrence time after initial treatment was followed up, and the correlation between newly diagnosed IgG level and recurrence was analyzed by univariate and multivariate analysis, as well as the influencing factors of IgG levels in order to predict furtherly the potential mechanism of recurrence. RESULTS: Univariate survival analysis showed that high revised international staging system (R-ISS) staging, high level of bone marrow plasma cell (BMPC), lactate dehydrogenase (LDH), creatinine, ß2-microglobulin, and IgG, low level of hemoglobin and serum albumin, high-risk genetic risk, autologous hematopoietic stem cell transplantation (ASCT) were closely related to shortened recurrence time after initial treatment (all P<0.05). COX multivariate survival analysis showed that high R-ISS staging, high level of BMPC, ß2-microglobulin, LDH, and IgG, low level of serum albumin, high-risk genetic risk, ASCT were independently associated with shorter recurrence time after initial treatment (all P<0.05). The median recurrence time of IgG MM patients with high and low IgG level was 30 (7-53) months and 42 (5-65) months, respectively. The cumulative recurrence rate of MM patients with high IgG level was significantly higher than that of patients with low level (χ2=7.982, P=0.005). Univariate analysis of the difference in IgG levels showed that high level of BMPC, urea nitrogen, blood creatinine, and low level of hemoglobin and serum albumin were closely related to high IgG level of IgG-type MM patients in initial diagnosis (all P<0.05). The logistic regression analysis of the differences in IgG levels showed that low level of serum albumin were independently correlated with high IgG levels in IgG-type MM patients in initial diagnosis (P<0.05). CONCLUSION: The higher the serum IgG concentration of IgG-type MM patients at first diagnosis, the earlier the recurrence, which is related to the low level of serum albumin, and can be used as a potential recurrence predictor after complete remission of IgG-type MM patients.

Pericytes augment glioblastoma cell resistance to temozolomide through CCL5-CCR5 paracrine signaling.

Glioblastoma (GBM) is a prevalent and highly lethal form of glioma, with rapid tumor progression and frequent recurrence. Excessive outgrowth of pericytes in GBM governs the ecology of the perivascular niche, but their function in mediating chemoresistance has not been fully explored. Herein, we uncovered that pericytes potentiate DNA damage repair (DDR) in GBM cells residing in the perivascular niche, which induces temozolomide (TMZ) chemoresistance. We found that increased pericyte proportion correlates with accelerated tumor recurrence and worse prognosis. Genetic depletion of pericytes in GBM xenografts enhances TMZ-induced cytotoxicity and prolongs survival of tumor-bearing mice. Mechanistically, C-C motif chemokine ligand 5 (CCL5) secreted by pericytes activates C-C motif chemokine receptor 5 (CCR5) on GBM cells to enable DNA-dependent protein kinase catalytic subunit (DNA-PKcs)-mediated DDR upon TMZ treatment. Disrupting CCL5-CCR5 paracrine signaling through the brain-penetrable CCR5 antagonist maraviroc (MVC) potently inhibits pericyte-promoted DDR and effectively improves the chemotherapeutic efficacy of TMZ. GBM patient-derived xenografts with high CCL5 expression benefit from combined treatment with TMZ and MVC. Our study reveals the role of pericytes as an extrinsic stimulator potentiating DDR signaling in GBM cells and suggests that targeting CCL5-CCR5 signaling could be an effective therapeutic strategy to improve chemotherapeutic efficacy against GBM.

Noninvasively Evaluating the Grading of Glioma by Multiparametric Magnetic Resonance Imaging.

RATIONALE AND OBJECTIVE: To investigate the performance of multi-parametric magnetic resonance imaging (MRI) for glioma grading. MATERIALS AND METHODS: Seventy consecutive patients with histopathologically confirmed glioma were retrospectively evaluated by conventional MRI, dynamic susceptibility-weighted contrast-enhanced, multiple diffusion-weighted imaging signal models including mono-exponential, bi-exponential, stretched exponential, and diffusion kurtosis imaging. One-way analysis of variance and independent-samples t test were used to compare the MR parameter values between low and high grades as well as among all grades of glioma. Receiver operating characteristic analysis, Spearman's correlation analysis, and binary logistic regression analysis were used to assess their diagnostic performance. RESULTS: The diagnostic performance (the optimal thresholds, area under the receiver operating characteristic curve, sensitivity, and specificity) was achieved with normalized relative cerebral blood flow (rCBV) (2.240 ml/100 g, 0.844, 87.8%, and 75.9%, respectively), mean kurtosis (MK) (0.471, 0.873, 92.7%, and 79.3%), and water molecular diffusion heterogeneity index (α) (1.064, 0.847, 79.3% and 78.0%) for glioma grading. There were positive correlations between rCBV and MK and the tumor grades and negative correlations between α and the tumor grades (p < 0.01). The parameter of α yielded a diagnostic accuracy of 85.3%, the combination of MK and α yielded a diagnostic accuracy of 89.7%, while the combination of rCBV, MK, and α were more accurate (94.2%) in predicting tumor grade. CONCLUSION: The most accurate parameters were rCBV, MK, and α in dynamic susceptibility-weighted contrast, diffusion kurtosis imaging, and Multi-b diffusion-weighted imaging for glioma grading, respectively. Multiparametric MRI can increase the accuracy of glioma grading.

Dataset for NiO/ZnO biomorphic nanocomposite using a poplar tree leaf template to generate an enhanced gas sensing platform to detect n-butanol.

The SEM image data presented in this article was collected by the Scanning electron microscopy (SEM) performed on an XL-30 ESEM FEG scanning electron microscopy. The diameter stastics data was collected and calculated by the Image-Pro Plus software system. The UV-Vis Res spectrum was collected by solid state UV diffuse reflector Shimadzu UV-4100 at wavelength 200-800 nm. The SEM image data showed more details of the poplar tree leave template(PTLT). The diameter stastics data show the diameter averagely distributed in the material. The UV-Vis Res spectrum reflected the physical property of PTLT NiO/ZnO. Interpretation of this data can be found in a research article titled "One-step facile synthesis of a NiO/ZnO biomorphic nanocomposite using a poplar tree leaf template to generate an enhanced gas sensing platform to detect n-butanol" (Qingrui Zeng et al., 2019) [1], Research Article DOI: 10.1016/j.jallcom.2019.05.018•The SEM image provide the more details about the distinction of the PTLT ZnO and conventional ZnO, further present more morphology information of the PTLT biotemplate. Exhibiting a facile and green way for synthesising ZnO and narrow down the size of ZnO crystal, present the advantage of PTLT ZnO in morphology control. Motivating gas sensor researcher to fabricate ZnO by a biotemplate method, which owned biomorphic and extraordinary gas sensing properties.•The UV-Vis Res spectrum present more detail of the energy band information of PTLT ZnO and PTLT NiO/ZnO, which is use for the gas sensing mechanism analysis. Inspiring researcher forcus on the construction on p-n heterojunction type gas sensor to enhance the gas sensing properties.•The material researchers work on the morphic investigation, gas sensor, and application of semiconductor.•These data are benefit for the application of biotemplate method for material fabrication and material application.

Gene testing for osteonecrosis of the femoral head in systemic lupus erythematosus using targeted next-generation sequencing: A pilot study.

BACKGROUND: Previous publications indicated that genetic predisposition might play important roles in the onset of osteonecrosis of the femoral head (ONFH) in systemic lupus erythematosus (SLE). Some gene loci such as complement C3d receptor 2 (CR2), nitric oxide synthase 3 (NOS3), collagen type II alpha 1 chain (COL2A1), protein tyrosine phosphatase non-receptor type 22 (PTPN22), and transient receptor potential cation channel subfamily V member 4 (TRPV4) were reported to be involved in this process. AIM: To investigate whether the risk of ONFH in SLE is associated with single nucleotide variations (SNVs) in these five genes. METHODS: SNVs in the CR2, NOS3, COL2A1, PTPN22, and TRPV4 genes were examined by using FastTarget and Illumina Miseq sequencing technologies in 49 cases of SLE with ONFH. Burrows-wheeler aligner was used to align the sequencing reads to hg19, and GATK and Varscan programs were used to perform SNV calling. PolyPhen-2, SIFT, and MutationTaster were used to assess the functional effects of non-synonymous SNVs. RESULTS: Six of the 49 patients were confirmed to have low frequency SNVs, including one patient with SNVs in NOS3 (exon 6: c.814G>A: p.E272K and exon 7: c.814G>A: p.E272K.), four in COL2A1 (rs41263847: exon 29: c.1913C>T: p.T638I, exon 28: c.1706C>T: p.T569I, and rs371445823: exon 8: c.580G>A: p.A194T, exon 7: c.373G>A: p.A125T), and one in CR2 (rs45573035: exon 2: c.200C>G: p.T67S). CONCLUSION: The onset of ONFH in SLE might be associated with the identified SNVs in NOS3, COL2A1, and CR2.

Rhein-PEG-nHA conjugate as a bone targeted drug delivery vehicle for enhanced cancer chemoradiotherapy.

Bone-targeted therapies have been the choice of treatments for cancer metastases in bone to minimize skeletal morbidity and preserve patients' quality of life. Rhein is of particular interest due to its high bone affinity. Here we reported a novel Rhein- polyethylene glycol (PEG)-nano hydroxyapatite (nHA) conjugate to deliver doxorubicin (DOX) and Phosphorus-32 (32P) simultaneously for enhanced cancer chemo-radiotherapy. The synthetic Rhein-PEG-nHA conjugates were sphere in shape with an average diameter of ~120 nm. Their morphology, drug release and bone affinity were confirmed in vitro. The release profiles of DOX depend on pH condition, but 32P exhibited good stability. Rhein-PEG-nHA also showed high bone affinity in vivo, and the tumor volume decreased after the DOX@Rhein-PEG-nHA and 32P@Rhein-PEG-nHA treatments. Most importantly, the DOX/32P@Rhein-PEG-nHA showed the strongest inhibition on the growth of bone metastases of breast cancer. We revealed the potential of Rhein-PEG-nHA in combined chemo-radiation treatment for bone metastases of breast cancer.