Publications by authors named "Yue Lu"

605 Publications

Coupling EGFR-antagonistic affibody enhanced therapeutic effects of cisplatin liposomes in EGFR-expressing tumor models.

J Pharm Sci 2021 Sep 18. Epub 2021 Sep 18.

Joint Laboratory for Translational Medicine Research, Liaocheng People's Hospital, Liaocheng, Shandong 252000, PR China. Electronic address:

Epidermal growth factor receptor (EGFR) is an efficient target for cancer therapy. In this study, a high-affinity EGFR-antagonistic affibody (Z) molecule coupled with cisplatin-loaded PEGylated liposomes (LS-DDP) was applied to actively target EGFR A431 tumor cells in vitro and in vivo. The LS-DDP coupled with Z (AS-DDP) had an average size of 140.01 ± 0.84 nm, low polydispersity, a zeta potential of -13.40 ± 0.8 mV, an acceptable encapsulation efficiency of 17.30 ± 1.35%, and released cisplatin in a slow-controlled manner. In vitro, AS-DDP demonstrated a higher amount of platinum intracellular uptake by A431 cells than LS-DDP. The IC50 value of AS-DDP (9.02 ± 1.55 μg/ml) was much lower than that of LS-DDP (16.44 ± 0.87 μg/ml), indicating that the anti-tumor effects of AS-DDP were remarkable due to the modification of Z. In vivo, the concentration of AS-DDP in the tumor site increased more than 1.76-fold, while an increase in apoptotic cells at 48 h compared to the LS-DDP was also observed, illustrating that AS-DDP possessed excellent tumor-targeting efficiency. As a result, the targeted nano-liposomes achieved greater tumor suppression. Therefore, selective targeting of LS-DDP coupled with Z enhanced the anti-tumor effects and appeared to be a promising strategy for the treatment of EGFR tumors.
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http://dx.doi.org/10.1016/j.xphs.2021.09.018DOI Listing
September 2021

Cuteness or Coolness-How Does Different Anthropomorphic Brand Image Accelerate Consumers' Willingness to Buy Green Products?

Front Psychol 2021 31;12:599385. Epub 2021 Aug 31.

School of Management, Jinan University, Guangzhou, China.

Green consumption is an important component of environmental protection behavior. The behaviors of individual consumers are having unprecedented impacts on the sustainable development of a green society. Previous research has discussed how anthropomorphic beneficiaries of environmental behavior (e.g., nature/earth) impact green consumption behavior and compared the influence of anthropomorphic presence and absence on consumers. However, few have examined the impact of different types of anthropomorphic carriers with environmental benefits (e.g., green product/brand) on consumers. This research explores the matching effects on the willingness of consumers to buy green products between the anthropomorphic image of the brand (cute vs. cool) and advertising appeals (self-interest vs. altruism); in addition, the underlying mechanisms of matching effects are revealed. The results show that, under the self-interested advertising appeal, the cool anthropomorphic image can lead to higher purchase intention of green products due to the mediating role played by the brand capacity trust. However, when exposed to altruistic advertising appeal, the cute anthropomorphic image can enhance brand goodwill trust of consumers and make consumers more willing to buy green products. Finally, this paper discusses the contributions and limitations.
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http://dx.doi.org/10.3389/fpsyg.2021.599385DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8438538PMC
August 2021

Palmitoylation of SARS-CoV-2 S protein is critical for S mediated syncytia formation and virus entry.

J Med Virol 2021 Sep 16. Epub 2021 Sep 16.

Department of Clinical Laboratory Medicine, The First Affifiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Jinan, Shandong, China.

SARS-CoV-2 causes the ongoing COVID-19 pandemic. S protein is the key viral protein for associating with ACE2, the receptor for SARS-CoV-2. There are many kinds of post-translational modifications in S protein. The mechanism of palmitoylation of SARS-CoV-2 S remains to be elucidated. In our current study, we characterized the palmitoylation of SARS-CoV-2 S. Both the C15 and cytoplasmic tail of SARS-CoV-2 S were palmitoylated. Fatty acid synthase inhibitor C75 and zinc finger DHHC domain-containing palmitoyltransferase (ZDHHC) inhibitor 2-BP reduced the palmitoylation of S. Interestingly, palmitoylation of SARS-CoV-2 S was not required for plasma membrane targeting of S, but was critical for S mediated syncytia formation and SARS-CoV-2 pseudovirus particle entry. Overexpression ZDHHC2, ZDHHC3, ZDHHC4, ZDHHC5, ZDHHC8, ZDHHC9, ZDHHC11, ZDHHC14, ZDHHC16, ZDHHC19 and ZDHHC20 promoted the palmitoylation of S. Furthermore, those ZDHHCs were identified to associate with SARS-CoV-2 S. Our study not only reveals the mechanism of S palmitoylation, but also will shed important light into the role of S palmitoylation in syncytia formation and virus entry. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1002/jmv.27339DOI Listing
September 2021

Altered Regional Homogeneity and Functional Connectivity during Microlesion Period after Deep Brain Stimulation in Parkinson's Disease.

Parkinsons Dis 2021 1;2021:2711365. Epub 2021 Sep 1.

Department of Functional Neurosurgery, The Affiliated Brain Hospital of Nanjing Medical University, Nanjing 210029, China.

Background: Patients with Parkinson's disease (PD) undergoing deep brain electrode implantation experience a temporary improvement in motor symptoms before the electrical stimulation begins. We usually call this the microlesion effect (MLE), but the mechanism behind it is not clear.

Purpose: This study aimed to assess the alterations in brain functions at the regional and whole-brain levels, using regional homogeneity (ReHo) and functional connectivity (FC), during the postoperative microlesion period after deep brain stimulation (DBS) in PD patients.

Method: Resting-state functional MRI data were collected from 27 PD patients before and after the first day of DBS and 12 healthy controls (HCs) in this study. The ReHo in combination with FC analysis was used to investigate the alterations of regional brain activity in all the subjects.

Results: There were increased ReHo in the basal ganglia-thalamocortical circuit (left supplementary motor area and bilateral paracentral lobule), whereas decreased ReHo in the default mode network (DMN) (left angular gyrus, bilateral precuneus), prefrontal cortex (bilateral middle frontal gyrus), and the cerebello-thalamocortical (CTC) circuit (Cerebellum_crus2/1_L) after DBS. In addition, we also found abnormal FC in the lingual gyrus, cerebellum, and DMN.

Conclusion: Microlesion of the thalamus caused by electrode implantation can alter the activity of the basal ganglia-thalamocortical circuit, prefrontal cortex, DMN, and CTC circuit and induce abnormal FC in the lingual gyrus, cerebellum, prefrontal cortex, and DMN among PD patients. The findings of this study contribute to the understanding of the mechanism of MLE.
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http://dx.doi.org/10.1155/2021/2711365DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8429001PMC
September 2021

Mammary-specific expression of Trim24 establishes a mouse model of human metaplastic breast cancer.

Nat Commun 2021 Sep 10;12(1):5389. Epub 2021 Sep 10.

The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Conditional overexpression of histone reader Tripartite motif containing protein 24 (TRIM24) in mouse mammary epithelia (Trim24) drives spontaneous development of mammary carcinosarcoma tumors, lacking ER, PR and HER2. Human carcinosarcomas or metaplastic breast cancers (MpBC) are a rare, chemorefractory subclass of triple-negative breast cancers (TNBC). Comparison of Trim24 metaplastic carcinosarcoma morphology, TRIM24 protein levels and a derived Trim24 gene signature reveals strong correlation with human MpBC tumors and MpBC patient-derived xenograft (PDX) models. Global and single-cell tumor profiling reveal Met as a direct oncogenic target of TRIM24, leading to aberrant PI3K/mTOR activation. Here, we find that pharmacological inhibition of these pathways in primary Trim24 tumor cells and TRIM24-PROTAC treatment of MpBC TNBC PDX tumorspheres decreased cellular viability, suggesting potential in therapeutically targeting TRIM24 and its regulated pathways in TRIM24-expressing TNBC.
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http://dx.doi.org/10.1038/s41467-021-25650-zDOI Listing
September 2021

Overexpression Leads to Aberrant Signal Transduction of Cancer-Related Pathways but Is Not Sufficient to Drive Tumor Formation in Mice.

Cancers (Basel) 2021 Aug 25;13(17). Epub 2021 Aug 25.

Department of Epigenetics and Molecular Carcinogenesis, University of Texas MD Anderson Cancer Center, Smithville, TX 78957, USA.

overexpression is observed in several human cancers and is correlated with poor patient outcomes. The molecular basis underlying this correlation is not clear. is the catalytic subunit of the deubiquitylation module in the SAGA histone-modifying complex, which regulates gene transcription. Our previous work demonstrated that the loss of in mice leads to decreased expression of several components of receptor tyrosine kinase and TGFβ signaling pathways. To determine whether these pathways are upregulated when is overexpressed, we created a mouse model that expresses high levels of in all tissues. Phenotypic characterization of these mice revealed over-branching of the mammary glands in females. Transcriptomic analyses indicate the upregulation of key pathways involved in mammary gland branching in mammary epithelial cells derived from the -overexpressing mice, including estrogen receptor, ERK/MAPK, and TGFβ signaling. However, overexpression did not lead to increased tumorigenesis in any tissue. Our findings indicate that elevated levels of are not sufficient to induce tumors, but it may enhance signaling abnormalities associated with oncogenesis.
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http://dx.doi.org/10.3390/cancers13174276DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8428332PMC
August 2021

SnRK1 stimulates the histone H3K27me3 demethylase JMJ705 to regulate a transcriptional switch to control energy homeostasis.

Plant Cell 2021 Sep 8. Epub 2021 Sep 8.

National Key Laboratory of Crop Genetic Improvement, Hubei Hongshan Laboratory, Huazhong Agricultural University, 430070 Wuhan, China.

Plant SNF1-Related Kinase1 (SnRK1) is an evolutionarily conserved energy sensing protein kinase that orchestrates transcriptional networks to maintain cellular energy homeostasis when energy supplies become limited. However, the mechanism by which SnRK1 regulates this gene expression switch to gauge cellular energy status remains largely unclear. In this work, we show that the rice histone H3K27me3 demethylase JMJ705 is required for low energy stress tolerance in rice plants. The genetic inactivation of JMJ705 resulted in similar effects as those of the rice snrk1 mutant on the transcriptome, which impair not only the promotion of the low energy stress-triggered transcriptional program but also the repression of the program under an energy-sufficient state. We show that the α-subunit of OsSnRK1 interacts with and phosphorylates JMJ705 to stimulate its H3K27me3 demethylase activity. Further analysis revealed that JMJ705 directly targets a set of low energy stress-responsive transcription factor genes. These results uncover the chromatin mechanism of SnRK1-regulated gene expression in both energy-sufficient and -limited states in plants and suggest that JMJ705 functions as an upstream regulator of the SnRK1α-controlled transcriptional network.
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http://dx.doi.org/10.1093/plcell/koab224DOI Listing
September 2021

Fuzhenghefuzhiyang Formula (FZHFZY) Improves Epidermal Differentiation Suppression of the Akt/mTORC1/S6K1 Signalling Pathway in Psoriatic Models.

Front Pharmacol 2021 11;12:650816. Epub 2021 Aug 11.

State Key Laboratory of Dampness Syndrome of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine (Guangdong Provincial Hospital of Chinese Medicine), Guangzhou, China.

Psoriasis is a chronic proliferative skin disorder characterised by abnormal epidermal differentiation. The Fuzhenghefuzhiyang (FZHFZY) formula created by Chuanjian Lu, a master of Chinese medicine in dermatology, has been external used in the Guangdong Provincial Hospital of Chinese Medicine for the treatment of psoriasis, but its mechanisms of action against psoriasis remain poorly understood. This study involved an exploration of the effects of FZHFZY on epidermal differentiation and its underlying mechanisms in interleukin (IL)-17A/IL-22/interferon (IFN)-γ/tumour necrosis factor (TNF)-α-stimulated HaCaT cells and in a mouse model of imiquimod (IMQ)-induced psoriasis. Cell viability was assessed by MTT assay. Epidermal differentiation was detected by reverse-transcription polymerase chain reaction and western blotting. Histological evaluation of the skin tissue was performed haematoxylin and eosin staining, and the Akt/mTORC1/S6K1 pathway was analysed by western blotting. FZHFZY inhibited proliferation and improved epidermal differentiation in IL-17A/IL-22/IFN-γ/TNF-α-induced HaCaT cells. FZHFZY ameliorated symptoms of psoriasis, regulated epidermal differentiation and inhibited phosphorylation of the Akt/mTORC1/S6K1 pathway in the skin of mice with imiquimod-induced psoriasis. Our results suggest that FZHFZY may exhibit therapeutic action against psoriasis by regulating epidermal differentiation inhibition of the Akt/mTORC1/S6K1 pathway.
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http://dx.doi.org/10.3389/fphar.2021.650816DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8386017PMC
August 2021

Trigonelline, An Alkaloid From Houtt., Suppresses Mast Cell Activation and OVA-Induced Allergic Asthma.

Front Pharmacol 2021 4;12:687970. Epub 2021 Aug 4.

School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, China.

Trigonelline, one of the active compounds from Houtt., has been proven to have pharmacological value in diabetes, the central nervous system and cardiovascular diseases. Recent studies have shown that it may also be beneficial in controlling inflammation. However, the mechanism of the antiallergic effects of trigonelline has not been well studied. As the key effector cells participating in the development of allergies, mast cells have been linked to the pathogenesis of asthma for ages. In this study, we demonstrated the inhibitory effect of trigonelline on activated bone marrow-derived mast cells (BMMCs) and verified its anti-inflammatory properties using an ovalbumin (OVA)-induced asthma model. Trigonelline suppressed BMMC degranulation and decreased the production of the cytokines, prostaglandin D (PGD) and leukotriene C (LTC) in a dose-dependent manner. The potent mechanism is mainly through the suppression of the nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways. Trigonelline can alleviate pathological damage in lung tissue and reduce the levels of serum immunoglobulin E (IgE) and T helper 2 (Th2) cytokines. RNA-seq results revealed the HIF-1α to be a potential target for the allergic reaction. Taken together, our study demonstrated that trigonelline can inhibit allergic inflammation and , which may provide a basis for novel anti-inflammatory drug development.
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http://dx.doi.org/10.3389/fphar.2021.687970DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8371462PMC
August 2021

New monoterpenoids from the stigmas of Crocus sativus.

J Nat Med 2021 Aug 21. Epub 2021 Aug 21.

School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Cai Lun Lu 1200, Shanghai, 201203, People's Republic of China.

One new compound, crocusatin M (1), and three new glycosidic compounds, crocusatins N-P (2-4), along with nine known compounds were isolated from the dried stigmas of Crocus sativus. The structures of new compounds were elucidated on the basis of spectroscopic analysis, and the absolute configurations of 1, 2, and 3 were unambiguously assigned by the comparison of experimental and calculated ECD data. This is the first report of the isolation of 4 with the HMG moiety from the genus Crocus. Compounds 1 and 4 exhibited weak anti-inflammatory activities on inhibiting lipopolysaccharide (LPS)-induced NO production.
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http://dx.doi.org/10.1007/s11418-021-01559-1DOI Listing
August 2021

Altered Spontaneous Neural Activity and Functional Connectivity in Parkinson's Disease With Subthalamic Microlesion.

Front Neurosci 2021 20;15:699010. Epub 2021 Jul 20.

Department of Functional Neurosurgery, The Affiliated Brain Hospital of Nanjing Medical University, Nanjing, China.

Background: Transient improvement in motor symptoms are immediately observed in patients with Parkinson's disease (PD) after an electrode has been implanted into the subthalamic nucleus (STN) for deep brain stimulation (DBS). This phenomenon is known as the microlesion effect (MLE). However, the underlying mechanisms of MLE is poorly understood.

Purpose: We utilized resting state functional MRI (rs-fMRI) to evaluate changes in spontaneous brain activity and networks in PD patients during the microlesion period after DBS.

Method: Overall, 37 PD patients and 13 gender- and age-matched healthy controls (HCs) were recruited for this study. Rs-MRI information was collected from PD patients three days before DBS and one day after DBS, whereas the HCs group was scanned once. We utilized the amplitude of low-frequency fluctuation (ALFF) method in order to analyze differences in spontaneous whole-brain activity among all subjects. Furthermore, functional connectivity (FC) was applied to investigate connections between other brain regions and brain areas with significantly different ALFF before and after surgery in PD patients.

Result: Relative to the PD-Pre-DBS group, the PD-Post-DBS group had higher ALFF in the right putamen, right inferior frontal gyrus, right precentral gyrus and lower ALFF in right angular gyrus, right precuneus, right posterior cingulate gyrus (PCC), left insula, left middle temporal gyrus (MTG), bilateral middle frontal gyrus and bilateral superior frontal gyrus (dorsolateral). Functional connectivity analysis revealed that these brain regions with significantly different ALFF scores demonstrated abnormal FC, largely in the temporal, prefrontal cortices and default mode network (DMN).

Conclusion: The subthalamic microlesion caused by DBS in PD was found to not only improve the activity of the basal ganglia-thalamocortical circuit, but also reduce the activity of the DMN and executive control network (ECN) related brain regions. Results from this study provide new insights into the mechanism of MLE.
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http://dx.doi.org/10.3389/fnins.2021.699010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8329380PMC
July 2021

Metabonomics Study on the Infertility Treated With Zishen Yutai Pills Combined With Fertilization-embryo Transfer.

Front Pharmacol 2021 19;12:686133. Epub 2021 Jul 19.

Molecular Biology and Systems Biology Team of Chinese Medicine, Guangdong Provincial Hospital of Chinese Medicine (The Second Clinical College of Guangzhou University of Chinese Medicine, Guangdong Provincial Academy of Chinese Medical Sciences), Guangzhou, China.

Zishen Yutai Pills (ZYP) is a safe and well quality-controlled TCM preparation with promising effects in many fields of reproduction, including prevention of miscarriage, increase of pregnancy rate during fertilization-embryo transfer (IVF-ET). The plasma of patients was collected from a clinical trial, namely, "Effect of Traditional Chinese Medicine vs placebo on live births among women undergoing fertilization, a multi-center randomized controlled trial." Plasma samples were analyzed with metabonomics method. UPLC-MS technology was used to establish the plasma metabolic fingerprint. Multivariate statistical analysis was applied for comparing the differences of plasma metabolites between ZYP group and placebo group, 44 potential metabolites were screen out and identified. Pathway analysis was conducted with database mining. Compared with placebo, chemicals were found to be significantly down-regulated on HCG trigger day and 14 days after embryo transplantation, including trihexosylceramide (d18:1/26:1), glucosylceramide(d18:1/26:0), TG(22:6/15:0/22:6), TG(22:4/20:4/18:4). Compared with placebo, some chemicals were found to be significantly up-regulated on HCG trigger day and 14 days after embryo transplantation, i.e., PIP3(16:0/16:1), PIP2(18:1/18:1), tauroursodeoxycholic acid, L-asparagine, L-glutamic acid, kynurenic acid, 11-deoxycorticosterone, melatonin glucuronide, hydroxytyrosol. These metabolites were highly enriched in pathways including sphingolipid metabolism, alanine, aspartic acid and glutamic acid metabolism, aminoacyl tRNA biosynthesis, taurine and hypotaurine metabolism. This study revealed metabolic differences between subjects administered with ZYP and placebo. Relating metabolites were identified and pathways were enriched, providing basis on the exploration on the underlying mechanisms of ZYP combined with IVF-ET in the treatment of infertility.
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http://dx.doi.org/10.3389/fphar.2021.686133DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8327273PMC
July 2021

Characterization of the complete chloroplast genome of the L. cv. Shepody (Solanaceae).

Mitochondrial DNA B Resour 2021 14;6(8):2342-2344. Epub 2021 Jul 14.

College of Horticulture, Jilin Agricultural University, Changchun City, P.R. China.

Potato ( L.), a species of the family Solanaceae, is the fourth most important food crop worldwide. L. cv. Shepody is a long, smooth, white-skinned potato cultivar with medium green leaves. It has good specific gravity and boils and bakes well. To support more molecular data for breeding of S. tuberosum, the complete chloroplast (cp) genome sequence of L. cv. Shepody was determined using the next-generation sequencing. In leaves, the chloroplast genome accounts for 3.88% of the total genome. The entire cp genome was determined to be 155,296 bp in length. It contained large single-copy (LSC) and small single-copy (SSC) regions of 85,737 and 18,373 bp, respectively, which were separated by a pair of 25,593 bp inverted repeat (IR) regions. The genome contained 132 total genes, including 87 protein-coding genes, 37 tRNA genes, and 8 rRNA genes. The overall GC content of the genome is 37.9%. A phylogenetic tree reconstructed by 60 chloroplast genomes reveals that L. cv. Shepody was closely related to S. tuberosum L. cv. Desiree with bootstrap support values of 100%.
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http://dx.doi.org/10.1080/23802359.2021.1934135DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8284121PMC
July 2021

β-Elemene suppresses hepatocellular carcinoma cell growth via mediating LncRNA HOTAIR / SP1 / PDK1 axis impact of β-elemene on hepatocellular carcinoma cells growth.

J Ethnopharmacol 2021 Jul 29:114456. Epub 2021 Jul 29.

The Second Clinical College, Guangzhou University of Chinese Medicine, Guangzhou 510120, Guangdong, China. Electronic address:

Ethnopharmacological Relevance: Hepatocellular carcinoma (HCC) is a liver malignancy which lacks effective treatment and with poor prognosis. β-Elemene refers to a series of natural Curcuma wenyujin-derived compounds, exerting lots of biological activities, which is especially famous for it's antitumor properties.

Aim Of The Research: Exploring the underlying mechanism of β-Elemene against HCC.

Materials And Methods: MTT, the assay of Colony formation and Flow cytometric were employed to evaluate the growth of HCC and LO2 cells by β-Elemene. HOTAIR、SP1 and PDK1 plasmids were transfected into HCC cells by transient transfection assay, and the expression and interaction of HOTAIR、SP1 and PDK1 were assessed via qRT-PCR and Western Blotting.

Results: β-Elemene suppressed HCC cell growth through downregulating HOTAIR, SP1 and PDK1. Mechanism experiments proved that there existed reciprocal interaction among HOTAIR, SP1 and PDK1. Exogenously overexpressed HOTAIR or SP1 eliminated the suppressive properties of β-Elemene on them, and both of which regulated PDK1 expression in HCC cells. Additionally, exogenously overexpressed SP1 or HOTAIR prevented β-Elemene inhibition of the protein-level expression of PDK1, whereas overexpressing PDK1 had no effect on SP1, though it still weakened the inhibition of cell growth and HOTAIR expression by β-Elemene.

Conclusion: β-Elemene suppresses HCC cell proliferation via through the regulation of HOTAIR/SP1/PDK1 axis and their interaction.
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http://dx.doi.org/10.1016/j.jep.2021.114456DOI Listing
July 2021

Phasing analysis of the transcriptome and epigenome in a rice hybrid reveals the inheritance and difference in DNA methylation and allelic transcription regulation.

Plant Commun 2021 Jul 15;2(4):100185. Epub 2021 Apr 15.

National Key Laboratory of Crop Genetic Improvement, College of Informatics, Huazhong Agricultural University, Wuhan 430070, China.

Hybrids are always a focus of botanical research and have a high practical value in agricultural production. To better understand allele regulation and differences in DNA methylation in hybrids, we developed a phasing pipeline for hybrid rice based on two parental genomes (PP2PG), which is applicable for Iso-Seq, RNA-Seq, and Bisulfite sequencing (BS-Seq). Using PP2PG, we analyzed differences in gene transcription, alternative splicing, and DNA methylation in an allele-specific manner between parents and progeny or different progeny alleles. The phasing of Iso-Seq data provided a great advantage in separating the whole gene structure and producing a significantly higher separation ratio than RNA-Seq. The interaction of hybrid alleles was studied by constructing an allele co-expression network that revealed the dominant allele effect in the network. The expression variation between parents and the parental alleles in progeny showed tissue- or environment-specific patterns, which implied a preference for -acting regulation under different conditions. In addition, by comparing allele-specific DNA methylation, we found that CG methylation was more likely to be inherited than CHG and CHH methylation, and its enrichment in genic regions was connected to gene structure. In addition to an effective phasing pipeline, we also identified differentiation in gene structure that may have led to the expansion of allele functions in hybrids. In summary, we developed a phasing pipeline and provided valuable insights into alternative splicing, interaction networks, acting regulation, and the inheritance of DNA methylation in hybrid rice.
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http://dx.doi.org/10.1016/j.xplc.2021.100185DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8299081PMC
July 2021

Low incidence rate of diarrhoea in COVID-19 patients is due to integrin.

J Infect 2021 Jul 15. Epub 2021 Jul 15.

Department of Laboratory Medicine, The First Affiliated Hospital of Shandong First Medical University, Jinan, Shandong, China; School of Basic Medicine, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong, China; Medical Science and Technology Innovation Center, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong, China. Electronic address:

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http://dx.doi.org/10.1016/j.jinf.2021.07.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8280609PMC
July 2021

Scutellarin improves the radiosensitivity of non-small cell lung cancer cells to iodine-125 seeds via downregulating the AKT/mTOR pathway.

Thorac Cancer 2021 Sep 13;12(17):2352-2359. Epub 2021 Jul 13.

Department of Interventional Medicine, The Second Hospital of Shandong University, Jinan, China.

Background: In our previous study, we indicated that scutellarin (SCU) induced an anticancer effect in A549 cells. However, whether SCU regulates the radiosensitivity of non-small cell lung cancer (NSCLC) and its related mechanism is still unclear.

Methods: In this study, we explored the anticancer effect induced by iodine-125 ( I) and SCU at a sensitizing concentration in A549 and H1975 cells. Cellular apoptosis and proliferation were detected by flow cytometry, Bcl-2/Bax expression level, cell cycle, CCK-8, and EdU staining. A tumor model using nude mice was also carried out to investigate the combined effect of I and SCU in vivo. In addition, the expression level of AKT/mTOR pathway was detected to investigate whether it is linked to the anticancer effect of I and SCU.

Results: SCU at a sensitizing concentration promoted the I-induced apoptosis and antiproliferative effect in A549 and H1975 cells. Moreover, the same results were obtained in vivo. Based on our findings, the AKT/mTOR pathway was significantly downregulated after combined treatment with I and SCU.

Conclusions: The results of our study suggested that SCU promotes the anticancer effects induced by I in NSCLC cells by downregulating the AKT/mTOR pathway and lays a foundation for future application of this combined treatment.
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http://dx.doi.org/10.1111/1759-7714.14077DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8410549PMC
September 2021

Characteristics of symptomatic plaque on high-resolution magnetic resonance imaging and its relationship with the occurrence and recurrence of ischemic stroke.

Neurol Sci 2021 Sep 8;42(9):3605-3613. Epub 2021 Jul 8.

Department of Neurology, The First Affiliated Hospital of Soochow University, No. 899, Pinghai Road, Suzhou, Jiangsu Province, China.

Background: Atherosclerosis is the most common cause of ischemia stroke. Computed tomographic angiography (CTA) and digital subtraction angiography (DSA) are used to evaluate the degree of lumen stenosis. However, these examinations are invasive and can only reveal mild to moderate stenosis. High-resolution magnetic resonance imaging (HRMRI) seems a more intuitive way to show the pathological changes of vascular wall. Hence, we conducted a systematic retrospective study to determine the characteristics of symptomatic plaques in patients with intracranial atherosclerosis on HRMRI and their association with the occurrence and recurrence of ischemic stroke events.

Methods: The PubMed database was searched for relevant studies reported from January 31, 2010, to October 31, 2020.

Results: We selected 14 clinical outcome studies. We found that plaque enhancement and positive remodeling on HRMRI indicate symptomatic plaques. Besides, intraplaque hemorrhage and positive remodeling index are closely related to the occurrence of stroke. However, it is still controversial whether the initial enhancement of plaque and the occurrence and recurrence of stroke are related. There is also no significant correlation between vascular stenosis and symptomatic plaque or the occurrence and recurrence of ischemic stroke.

Conclusion: High-resolution magnetic resonance imaging can be used as an assessment tool to predict the risk of stroke onset and recurrence in patients with atherosclerosis, but further research is also needed.
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http://dx.doi.org/10.1007/s10072-021-05457-yDOI Listing
September 2021

Gadolinium enhancement of atherosclerotic plaque in the intracranial artery.

Neurol Res 2021 Jul 6:1-10. Epub 2021 Jul 6.

Department of Neurology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China.

: Gadolinium enhancement on high resolution magnetic resonance imaging (HR-MRI) has been considered a sign of instability and inflammation of intracranial atherosclerotic plaques. Our research objective was to explore the relationship between the extent of plaque enhancement (PE), the degree of intracranial artery stenosis, and acute ischemic stroke events. HR-MRI was performed in 91 patients with intracranial vascular stenosis to determine the existence and intensity of PE. Among 91 patients enrolled in the trial, there were 43 patients in the acute/subacute group (≤1 month from ischemic stroke event), 15 patients in the chronic group (>1 month from ischemic stroke event), and 33 patients in the non-culprit plaques group (no ischemic stroke event). A total of 105 intracranial atherosclerotic plaques were detected in 91 patients. 14 (13.3%) were mild-stenosis plaques, 22 (21.0%) were moderate-stenosis plaques, and 69 (65.7%) were severe-stenosis plaques. There were 12 (11.4%), 18 (17.1%), and 75 (71.4%) plaques in the non-enhanced plaque group, the mild-enhancement group, and the significant-enhancement group, respectively. The degree of PE among the acute/subacute group, the chronic group, and the non-culprit plaque group had a significant difference (P = 0.005). Enhanced plaques were more often observed in culprit plaques (acute/subacute group and chronic group) than non-culprit plaques (96.7% vs 77.3%). Non-enhanced plaques were more often observed in non-culprit plaques than culprit plaques (acute/subacute group and chronic group) (22.7% vs 3.3%). And 36.6% of the enhanced plaques were non-culprit plaques. After performing univariate and multivariate logistic regression analysis, the results showed that strong plaque enhancement (P = 0.025, odds ratio [OR] 3.700, 95% confidence interval [95% CI] 1.182-11.583) and severe stenosis (P = 0.008, OR 4.393, 95%CI 1.481-13.030) were significantly associated with acute ischemic events. Enhanced plaques were more often observed in culprit plaques, and non-enhanced plaques were more often observed in non-culprit plaques. Moreover, significant plaque enhancement and severe ICAS were closely associated with acute ischemic events.
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http://dx.doi.org/10.1080/01616412.2021.1949682DOI Listing
July 2021

Resolution of tissue signatures of therapy response in patients with recurrent GBM treated with neoadjuvant anti-PD1.

Nat Commun 2021 06 29;12(1):4031. Epub 2021 Jun 29.

Institute for Systems Biology, Seattle, WA, USA.

The response of patients with recurrent glioblastoma multiforme to neoadjuvant immune checkpoint blockade has been challenging to interpret due to the inter-patient and intra-tumor heterogeneity. We report on a comparative analysis of tumor tissues collected from patients with recurrent glioblastoma and high-risk melanoma, both treated with neoadjuvant checkpoint blockade. We develop a framework that uses multiplex spatial protein profiling, machine learning-based image analysis, and data-driven computational models to investigate the pathophysiological and molecular factors within the tumor microenvironment that influence treatment response. Using melanoma to guide the interpretation of glioblastoma analyses, we interrogate the protein expression in microscopic compartments of tumors, and determine the correlates of cytotoxic CD8+ T cells, tumor growth, treatment response, and immune cell-cell interaction. This work reveals similarities shared between glioblastoma and melanoma, immunosuppressive factors that are unique to the glioblastoma microenvironment, and potential co-targets for enhancing the efficacy of neoadjuvant immune checkpoint blockade.
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http://dx.doi.org/10.1038/s41467-021-24293-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8241935PMC
June 2021

Phosphine-Catalyzed Intermolecular Dienylation of Alkynoate with -Quinone Methides.

J Org Chem 2021 07 24;86(13):8590-8599. Epub 2021 Jun 24.

Molecular Synthesis Center, Key Laboratory of Marine Drugs, Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, 23 Hongkong East Road, Qingdao 266071, Shandong Province, China.

An interesting remote δ-C 1,6-addition and an isomerization cascade reaction for phosphine-catalyzed activated alkynes have been disclosed. The products featuring a functional diene and a 1,1-diaryl methyl motif have been obtained in moderate to good yields (30-86%) by applying -quinone methides (QMs) and δ-substituted alkynoate with tributylphosphine (PBu) catalysis, along with high regioselectivity and stereoselectivity (dr > 20:1). The wide scope of compatible substrates (35 examples), such as indolyl, oxindolyl, ester, and cinnamyl, expand the utility of this methodology. A plausible mechanism and some applications of it have also been presented.
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http://dx.doi.org/10.1021/acs.joc.1c00226DOI Listing
July 2021

Effects and mechanisms of modified biochars on microbial iron reduction of Geobacter sulfurreducens.

Chemosphere 2021 Nov 3;283:130983. Epub 2021 Jun 3.

College of Environmental Science and Engineering, Hunan University, Changsha, 410082, Hunan, China; Key Laboratory of Environmental Biology and Pollution Control (Hunan University), Ministry of Education, Changsha, 410082, Hunan, China.

Biochar was proved as an electron shuttle to facilitate extracellular electron transfer (EET) of electrochemically active bacteria (EAB); however, its underlying mechanism was not fully understood. In this study, we aimed to further explore how the regulation of surface functional groups of biochar would affect the microbial iron reduction process of Geobacter sulfurreducens as a typical EAB. Two modified biochars were achieved after HNO (NBC) and NaBH (RBC) pretreatments, and a control biochar was produced after deionized water (WBC) washing. Results showed that WBC and RBC significantly accelerated microbial iron reduction of G. sulfurreducens PCA, while had no effect in the final Fe (II) minerals (e.g., vivianite and green rust (CO)). Besides, Brunauer-Emmett-Teller (BET) surface area, electron spin resonance (ESR) and electrochemical measurements showed that larger surface area, lower redox potential, and more redox-active groups (e.g., aromatic structures and quinone/hydroquinone moieties) in RBC explained its better electron transfer performance comparing to WBC. Interestingly, NBC completely suppressed the Fe (III) reduction process, mainly due to the production of reactive oxygen species which inhibited the growth of G. sulfurreducens PCA. Overall, this work paves a feasible way to regulate the surface functional groups for biochar, and comprehensively revealed its effect on EET process of microorganisms.
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http://dx.doi.org/10.1016/j.chemosphere.2021.130983DOI Listing
November 2021

Identification of a prognostic metabolic gene signature in diffuse large B-cell lymphoma.

J Cell Mol Med 2021 Jul 14;25(14):7066-7077. Epub 2021 Jun 14.

Sun Yat-sen University Cancer Center, Guangzhou, China.

Diffuse large B-cell lymphoma (DLBCL) is a clinically diverse disease. Given the numerous genetic mutations and variations associated with it, a prognostic gene signature that can be related to the overall survival (OS) is a clinical implication. We used the mRNA expression profiles and clinicopathological data of patients with DLBCL from the Gene Expression Omnibus (GEO) database to identify a metabolism-related gene signature. Using LASSO regression analysis, a novel 13-metabolic gene signature was identified to evaluate prognosis. The information gathered was used to construct the nomogram model to improve risk stratification and quantify risk factors for individual patients. We performed gene set enrichment analysis to identify the enriched signalling axes to further understand the underlying biological pathways. The receiver operating characteristic (ROC) curve revealed a satisfactory performance in the training cohorts. The model also showed clinical benefit when compared to the standard prognostic factors (P < .05) in validation cohorts. This study aimed to combine metabolic dysregulation with clinical features of patients with DLBCL to generate a prognostic model that might not only indicate the value of the metabolic microenvironment for prognostic stratification but also improve the decision-making during individual therapy.
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http://dx.doi.org/10.1111/jcmm.16720DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8278125PMC
July 2021

Safranal Alleviated OVA-Induced Asthma Model and Inhibits Mast Cell Activation.

Front Immunol 2021 20;12:585595. Epub 2021 May 20.

School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, China.

Introduction: Asthma is a chronic and recurring airway disease, which related to mast cell activation. Many compounds derived from Chinese herbal medicine has promising effects on stabilizing mast cells and decreasing inflammatory mediator production. Safranal, one of the active compounds from , shows many anti-inflammatory properties. In this study, we evaluated the effect of safranal in ovalbumin (OVA)-induced asthma model. Furthermore, we investigate the effectiveness of safranal on stabilizing mast cell and inhibiting the production of inflammatory mediators in passive systemic anaphylaxis (PSA) model.

Methods: OVA-induced asthma and PSA model were used to evaluate the effect of safranal Lung tissues were collected for H&E, TB, IHC, and PAS staining. ELISA were used to determine level of IgE and chemokines (IL-4, IL-5, TNF-α, and IFN-γ). RNA sequencing was used to uncovers genes that safranal regulate. Bone marrow-derived mast cells (BMMCs) were used to investigate the inhibitory effect and mechanism of safranal. Cytokine production (IL-6, TNF-α, and LTC) and NF-κB and MAPKs signaling pathway were assessed.

Results: Safranal reduced the level of serum IgE, the number of mast cells in lung tissue were decreased and Th1/Th2 cytokine levels were normalized in OVA-induced asthma model. Furthermore, safranal inhibited BMMCs degranulation and inhibited the production of LTC, IL-6, and TNF-α. Safranal inhibits NF-κB and MAPKs pathway protein phosphorylation and decreases NF-κB p65, AP-1 nuclear translocation. In the PSA model, safranal reduced the levels of histamine and LTC in serum.

Conclusions: Safranal alleviates OVA-induced asthma, inhibits mast cell activation and PSA reaction. The possible mechanism occurs through the inhibition of the MAPKs and NF-κB pathways.
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http://dx.doi.org/10.3389/fimmu.2021.585595DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8173045PMC
July 2021

Efficient Gradient Potential Top Electron Transport Structures Achieved by Combining an Oxide Family for Inverted Perovskite Solar Cells with High Efficiency and Stability.

ACS Appl Mater Interfaces 2021 Jun 4;13(23):27179-27187. Epub 2021 Jun 4.

Department of Electrical and Electronic Engineering, The University of Hong Kong, Pokfulam Road, Hong Kong 999077, China.

Although inverted (p-i-n) structure perovskite solar cells (PSCs) have achieved high efficiency by commonly using fullerenes or their derivatives as electron transport layers (ETLs), the device stability and cost of fullerene materials are still of great concern. Herein, we demonstrate inorganic top ETLs simply composed from a family of metal oxides including InO and its derivative of Sn:InO with a gradient potential structure. For inverted PSCs, the typical film formation process of InO will damage or degrade perovskite materials underneath; thus, we report a low temperature synthesis approach for obtaining InO and Sn:InO nanoparticles that can form effective top ETLs without any post-treatment. The one-family oxide-based top ETL features with the enhanced built-in potential, high electron extraction, and low interfacial recombination, offering a power conversion efficiency (PCE) of 20.65% in PSCs constructed from oxide-only carrier (both hole and electron) transport layers (CTLs), which is the highest efficiency in oxide-only CTL-based inverted PSCs to the best of our knowledge. Equally important, the inverted PSCs based on the Sn:InO/InO ETL show the excellent operational stability and remain 90% of the initial value of PCE over 2000 h. Consequently, this work contributes to the robust strategy of all oxide-only CTLs in developing rigid and flexible PSCs for practical photovoltaic applications.
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http://dx.doi.org/10.1021/acsami.1c05284DOI Listing
June 2021

High-resolution genome-wide association study and genomic prediction for disease resistance and cold tolerance in wheat.

Theor Appl Genet 2021 Sep 1;134(9):2857-2873. Epub 2021 Jun 1.

State Key Laboratory of Crop Biology, College of Agronomy, Shandong Agricultural University, Tai'an 271018, China.

Key Message: High-resolution genome-wide association study (GWAS) facilitated QTL fine mapping and candidate gene identification, and the GWAS based genomic prediction models were highly predictive and valuable in wheat genomic breeding. Wheat is a major staple food crop and provides more than one-fifth of the daily calories and dietary proteins for humans. Genome-wide association study (GWAS) and genomic selection (GS) for wheat stress resistance and tolerance related traits are critical to understanding their genetic architecture for improvement of breeding selection efficiency. However, the insufficient marker density in previous studies limited the utility of GWAS and GS in wheat genomic breeding. Here, we conducted a high-resolution GWAS for wheat leaf rust (LR), yellow rust (YR), powdery mildew (PM), and cold tolerance (CT) by genotyping a panel of 768 wheat cultivars using genotyping-by-sequencing. Among 153 quantitative trait loci (QTLs) identified, 81 QTLs were delimited to ≤ 1.0 Mb intervals with three validated using bi-parental populations. Furthermore, 837 stress resistance-related genes were identified in the QTL regions with 12 showing induced expression by YR and PM pathogens. Genomic prediction using 2608, 4064, 3907, and 2136 pre-selected SNPs based on GWAS and genotypic correlations between the SNPs showed high prediction accuracies of 0.76, 0.73, and 0.78 for resistance to LR, YR, and PM, respectively, and 0.83 for resistance to cold damage. Our study laid a solid foundation for large-scale QTL fine mapping, candidate gene validation and GS in wheat.
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http://dx.doi.org/10.1007/s00122-021-03863-6DOI Listing
September 2021

Design, Synthesis, and Evaluation of -(Biphenyl-3-ylmethoxy)nitrophenyl Derivatives as PD-1/PD-L1 Inhibitors with Potent Anticancer Efficacy .

J Med Chem 2021 06 26;64(11):7646-7666. Epub 2021 May 26.

State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, Center of Drug Discovery, China Pharmaceutical University, Nanjing 210009, PR China.

Two series of novel -(biphenyl-3-ylmethoxy)nitrophenyl compounds ( and ) were designed as programmed cell death protein 1 (PD-1)/PD-ligand 1 (PD-L1) inhibitors. All compounds showed significant inhibitory activity with IC values ranging from 2.7 to 87.4 nM except compound , and compound displayed the best activity. Further experiments showed that bound to the PD-L1 protein without obvious toxicity in Lewis lung carcinoma (LLC) cells. Furthermore, significantly promoted interferon-gamma secretion in a dose-dependent manner and . Especially, exhibited potent anticancer efficacy in an LLC-bearing allograft mouse model at a low dose of 5 mg/kg, which was more active than BMS-1018 (tumor growth inhibition rate: 48.5% vs 17.8%). A panel of immunohistochemistry and flow cytometry assays demonstrated that effectively counteracted PD-1-induced immunosuppression in the tumor microenvironment, thereby triggering antitumor immunity. These results indicate that is a promising PD-1/PD-L1 inhibitor worthy of further development.
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http://dx.doi.org/10.1021/acs.jmedchem.1c00370DOI Listing
June 2021

The arsenic chemical species proportion and viral arsenic biotransformation genes composition affects lysogenic phage treatment under arsenic stress.

Sci Total Environ 2021 Aug 20;780:146628. Epub 2021 Mar 20.

College of Environmental Science and Engineering, Hunan University and Key Laboratory of Environmental Biology and Pollution Control (Hunan University), Ministry of Education, Changsha 410082, PR China.

When temperate phages and their hosts have a consistent interest, they are considered reciprocal. Based on the bacterium-phage collaboration, lysogenic phage treatment is a promising method to resist pollution through lysogenic phage reshaping indigenous microbial communities to maintain their ecological function under environmental stress. However, the potential factors affecting the establishment of bacterium-phage collaboration are still poorly understood. Here, lysogenic phages carrying arsenic biotransformation genes (ABGs) were induced from the enriched arsenic-resistant microorganisms (from arsenic-contaminated sites). The diversity analysis of viral arsC and arsM demonstrated that arsM tended to proliferate rapidly under high arsenic levels, and the transduction of arsM might be the key to lysogenic phages to help the hosts relieve the stress of high arsenic. Microcosm experiments confirmed that with the increase of the As(III) content (0% to 50%, of 200 mg/kg total arsenic) in the soil, inoculation of lysogenic phages with both arsC and arsM resulted in more transduction of arsM (0.06 ± 0.007 to 0.23 ± 0.024 per 16S rRNA) among soil microorganisms. In contrast, inoculation of lysogenic phages carrying the only arsC transduces more arsC (0.12 ± 0.037 to 0.315 ± 0.051 per 16S rRNA) compare with the control. This article confirmed that different arsenic species proportions and different viral gene compositions could change the abundance of ABGs in the soil microbe, which might provide basic knowledge for further understanding of arsenic pollution control mediated by lysogenic phage.
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http://dx.doi.org/10.1016/j.scitotenv.2021.146628DOI Listing
August 2021

Integrating CAR T-Cell Therapy and Transplantation: Comparisons of Safety and Long-Term Efficacy of Allogeneic Hematopoietic Stem Cell Transplantation After CAR T-Cell or Chemotherapy-Based Complete Remission in B-Cell Acute Lymphoblastic Leukemia.

Front Immunol 2021 7;12:605766. Epub 2021 May 7.

Department of Hematology and Immunology, Hebei Yanda Lu Daopei Hospital, Langfang, China.

Patients often undergo consolidation allogeneic hematopoietic stem cell transplantation (allo-HSCT) to maintain long-term remission following chimeric antigen receptor (CAR) T-cell therapy. Comparisons of safety and efficacy of allo-HSCT following complete remission (CR) achieved by CAR-T therapy  by chemotherapy for B-cell acute lymphoblastic leukemia (B-ALL) has not been reported. We performed a parallel comparison of transplant outcomes in 105 consecutive B-ALL patients who received allo-HSCT after achieving CR with CAR-T therapy (n=27) or with chemotherapy (n=78). The CAR-T-allo-HSCT group had more patients in second CR compared to the chemotherapy-allo-HSCT group (78%  37%; p<0.01) and more with complex cytogenetics (44%  6%; p<0.001) but the proportion of patients with pre-transplant minimal residual disease (MRD) was similar. The median follow-up time was 49 months (range: 25-54 months). The CAR-T cohort had a higher incidence of Grade II-IV acute graft--host disease (aGVHD 48.1% [95% CI: 46.1-50.1%] 25.6% [95%CI: 25.2-26.0%]; p=0.016). The incidence of Grade III-IV aGVHD was similar in both groups (11.1% 11.5%, p=0.945). The overall incidence of chronic GVHD in the CAR-T group was higher compared to the chemotherapy group (73.3% [95%CI: 71.3-75.3%] 55.0% [95%CI: 54.2-55.8%], p=0.107), but the rate of extensive chronic GVHD was similar (11.1% 11.9%, p=0.964). Efficacy measures 4 years following transplant were all similar in the CAR-T the chemotherapy groups: cumulative incidences of relapse (CIR; 11.1% vs.12.8%; p=0.84), cumulative incidences of non-relapse mortality (NRM; 18.7% 23.1%; p=0.641) leukemia-free survival (LFS; 70.2% 64.1%; p=0.63) and overall survival (OS; 70.2% 65.4%; p=0.681). We found that pre-transplant MRD-negative CR predicted a lower CIR and a higher LFS compared with MRD-positive CR. In conclusion, our data indicate that, in B-ALL patients, similar clinical safety outcomes could be achieved with either CD19 CAR T-cell therapy followed by allo-HSCT or chemotherapy followed by allo-HSCT. Despite the inclusion of more patients with advanced diseases in the CAR-T group, the 4-year LFS and OS achieved with CAR T-cells followed by allo-HSCT were as remarkable as those achieved with chemotherapy followed by allo-HSCT. Further confirmation of these results requires larger, randomized clinical trials.
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http://dx.doi.org/10.3389/fimmu.2021.605766DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8138447PMC
June 2021

Anti-Angiogenic Efficacy of PSORI-CM02 and the Associated Mechanism in Psoriasis and .

Front Immunol 2021 30;12:649591. Epub 2021 Apr 30.

The Second Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, China.

Psoriasis is a chronic proliferative autoimmune dermatologic disease characterised by abnormal angiogenesis. Thus, regulating angiogenesis in the skin is an important treatment strategy for psoriasis. PSORI-CM02, an empirical Chinese medicine formula optimised from Yin Xie Ling, was created by the Chinese medicine specialist, Guo-Wei Xuan. Clinical studies have shown that PSORI-CM02 is safe and effective for the treatment of psoriasis. However, its anti-psoriatic mechanisms remain to be further explored. In this study, we investigated the effects of PSORI-CM02 on angiogenesis in the skin and the underlying mechanisms in IL-17A-stimulated human umbilical vein endothelial cells (HUVECs) and a murine model of imiquimod (IMQ)-induced psoriasis. , PSORI-CM02 significantly inhibited the proliferation and migration of IL-17A-stimulated HUVECs in a dose-dependent manner. Further, it markedly regulated the antioxidative/oxidative status and inflammation; suppressed the expression of VEGF, VEGFR1, VEGFR2, ANG1, and HIF-1α; and reduced the phosphorylation of MAPK signalling pathway components in IL-17A-stimulated HUVECs. studies showed that PSORI-CM02 markedly reduced angiogenesis in the skin of mice with IMQ-induced psoriasis, while significantly rebalancing antioxidant/oxidant levels; inhibiting the production of IL-6, TNF-α, IL-17A, and IL-17F; and repressing the synthesis of angiogenic mediators. In addition, PSORI-CM02 markedly reduced the activation of the MAPK signalling pathway in psoriatic skin tissue. Taken together, our results demonstrated that PSORI-CM02 inhibited psoriatic angiogenesis by reducing the oxidative status and inflammation, suppressing the expression of angiogenesis-related molecules, and inhibiting the activation of the MAPK signalling pathway and .
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http://dx.doi.org/10.3389/fimmu.2021.649591DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8119787PMC
April 2021
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