Publications by authors named "Zhiqiang Wu"

234 Publications

Pharmacokinetic Characteristics, Tissue Bioaccumulation and Toxicity Profiles of Oral Arsenic Trioxide in Rats: Implications for the Treatment and Risk Assessment of Acute Promyelocytic Leukemia.

Front Pharmacol 2021 28;12:647687. Epub 2021 May 28.

Department of Pharmacy, The First Affiliated Hospital of Harbin Medical University, Harbin, China.

Oral arsenic trioxide (ATO) has demonstrated a favorable clinical efficiency in the treatment of acute promyelocytic leukemia (APL). However, the pharmacokinetic characteristics, tissue bioaccumulation, and toxicity profiles of arsenic metabolites following oral administration of ATO have not yet been characterized. The present study uses high performance liquid chromatography-hydride generation-atomic fluorescence spectrometry (HPLC-HG-AFS) to assess the pharmacokinetics of arsenic metabolites in rat plasma after oral and intravenous administration of 1 mg kg ATO. In addition, the bioaccumulation of arsenic metabolites in blood and selected tissues were evaluated after 28 days oral administration of ATO in rats at a dose of 0, 2, 8, and 20 mg kg d. The HPLC-HG-AFS analysis was complemented by a biochemical, hematological, and histopathological evaluation conducted upon completion of ATO treatment. Pharmacokinetic results showed that arsenite (As) reached a maximum plasma concentration rapidly after initial dosing, and the absolute bioavailability of As was 81.03%. Toxicological results showed that the levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and white blood cells (WBC) in the 20 mg kg d ATO group were significantly increased compared to the control group ( < 0.05). The distribution trend of total arsenic in the rat was as follows: whole blood > kidney > liver > heart. Dimethylated arsenic (DMA) was the predominant bioaccumulative metabolite in the whole blood, liver, and heart, while monomethylated arsenic (MMA) was the predominant one in the kidney. Collectively, these results revealed that oral ATO was rapidly absorbed, well-tolerated, and showed organ-specific and dose-specific bioaccumulation of arsenic metabolites. The present study provides preliminary evidence for clinical applications and the long-term safety evaluation of oral ATO in the treatment of APL.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fphar.2021.647687DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8194082PMC
May 2021

STAT3/miR-135b/NF-κB axis confers aggressiveness and unfavorable prognosis in non-small-cell lung cancer.

Cell Death Dis 2021 May 14;12(5):493. Epub 2021 May 14.

Department of Radiation Oncology, Tianjin Medical University Cancer Institute & Hospital, Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, 300060, Tianjin, China.

Non-small-cell lung cancer (NSCLC) is one of the most commonly diagnosed cancers worldwide but has limited effective therapies. Uncovering the underlying pathological and molecular changes, as well as mechanisms, will improve the treatment. Dysregulated microRNAs (miRNAs) have been proven to play important roles in the initiation and progression of various cancers, including NSCLC. In this manuscript, we identified microRNA-135b (miR-135b) as a tumor-promoting miRNA in NSCLC. We found that miR-135b was significantly upregulated and that its upregulation was associated with poor prognosis in NSCLC patients. miR-135b was an independent prognostic factor in NSCLC. Overexpressing miR-135b significantly promoted the aggressiveness of NSCLC, as evidenced by enhanced cell proliferation, migration, invasion, anti-apoptosis, and angiogenesis in vitro and in vivo, and knockdown of miR-135b had the opposite effects. Mechanistically, our results reveal that miR-135b directly targets the 3'-untranslated region (UTR) of the deubiquitinase CYLD, thereby modulating ubiquitination and activation of NF-κB signaling. Moreover, we found that interleukin-6 (IL-6)/STAT3 could elevate miR-135b levels and that STAT3 directly bound the promoter of miR-135b; thus, these findings highlight a new positive feedback loop of the IL-6/STAT3/miR-135b/NF-κB signaling in NSCLC and suggest that miR-135b could be a potential therapeutic target for NSCLC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41419-021-03773-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8121828PMC
May 2021

Chloroplast genomes in Populus (Salicaceae): comparisons from an intensively sampled genus reveal dynamic patterns of evolution.

Sci Rep 2021 May 4;11(1):9471. Epub 2021 May 4.

Shenzhen Branch, Guangdong Laboratory for Lingnan Modern Agriculture, Genome Analysis Laboratory of the Ministry of Agriculture, Agricultural Genomics Institute at Shenzhen, Chinese Academy of Agricultural Sciences, Shenzhen, 518120, China.

The chloroplast is one of two organelles containing a separate genome that codes for essential and distinct cellular functions such as photosynthesis. Given the importance of chloroplasts in plant metabolism, the genomic architecture and gene content have been strongly conserved through long periods of time and as such are useful molecular tools for evolutionary inferences. At present, complete chloroplast genomes from over 4000 species have been deposited into publicly accessible databases. Despite the large number of complete chloroplast genomes, comprehensive analyses regarding genome architecture and gene content have not been conducted for many lineages with complete species sampling. In this study, we employed the genus Populus to assess how more comprehensively sampled chloroplast genome analyses can be used in understanding chloroplast evolution in a broadly studied lineage of angiosperms. We conducted comparative analyses across Populus in order to elucidate variation in key genome features such as genome size, gene number, gene content, repeat type and number, SSR (Simple Sequence Repeat) abundance, and boundary positioning between the four main units of the genome. We found that some genome annotations were variable across the genus owing in part from errors in assembly or data checking and from this provided corrected annotations. We also employed complete chloroplast genomes for phylogenetic analyses including the dating of divergence times throughout the genus. Lastly, we utilized re-sequencing data to describe the variations of pan-chloroplast genomes at the population level for P. euphratica. The analyses used in this paper provide a blueprint for the types of analyses that can be conducted with publicly available chloroplast genomes as well as methods for building upon existing datasets to improve evolutionary inference.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-021-88160-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8096831PMC
May 2021

Monomethylated arsenic was the Major methylated arsenic in Red blood cells of acute promyelocytic leukemia patients treated with arsenic trioxide.

Toxicol Lett 2021 Sep 15;347:78-85. Epub 2021 Apr 15.

Department of Pharmacy, The First Affiliated Hospital of Harbin Medical University, 23 You-Zheng Street, Harbin, 150001, China. Electronic address:

Background: Arsenic trioxide (ATO) has been successfully applied in the treatment of acute promyelocytic leukemia (APL). Arsenic metabolites including inorganic arsenic and methylated arsenic could lead to different toxicity and curative effect. This study aims to establish a method to determine arsenic species in red blood cells (RBCs), clarify the distribution characteristics of arsenic species in RBCs.

Methods: Steady state blood samples were collected from 97 APL patients. HO and HClO were used to release the hemoglobin bounding arsenic and precipitate protein. Arsenite (iAs), arsenate (iAs), monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA) in plasma and RBCs were detected by HPLC-HG-AFS. Free and bound arsenic species in RBCs were separated by 30 kDa molecular mass cutoff filters and determined to evaluate hemoglobin binding capacity of different arsenic species.

Results: The method was validated with accuracy ranged from 84.75% to 104.13%. Arsenic species in RBCs followed the trend iAs > MMA > DMA (p < 0.01), while the concentration of DMA was significantly higher than iAs and MMA in plasma (p < 0.01). The correlation between iAs concentration in plasma and corresponding RBCs arsenic level was weak. And the concentrations of DMA and MMA in plasma were moderately positive correlated with those in RBCs. Hemoglobin-binding ratios of iAs, MMA and DMA were all over 70 %.

Conclusions: In this study, we provided a reliable method to determine arsenic species in RBCs of APL patients treated with ATO by HPLC-HG-AFS. It was confirmed that the concentration of DMA is the highest in plasma, while MMA is the most predominant methylated arsenic in RBCs. High affinity of MMA with human Hb was responsible for the accumulation of arsenic in RBCs of APL patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.toxlet.2021.04.005DOI Listing
September 2021

"Without the need for a second visit" initiative improves patient satisfaction with updated services of outpatient clinics in China.

BMC Health Serv Res 2021 Mar 23;21(1):267. Epub 2021 Mar 23.

Department of Medical Administration, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, No.158 Shangtang Road, Zhejiang, Hangzhou, China.

Background: To implement the "without the need for a second visit" (WNASV) initiative in our hospital by optimizing the outpatient clinic services via an upgraded information system, in order to increase the quality of outpatient medical services and improve patients' satisfaction.

Methods: An Internet-based care delivery approach was developed and applied to improve the delivery of health care services, simplify the treatment process, and reduce patient waiting time. The patient waiting time and consultation time in the outpatient clinics of our hospital during the peak service intervals and the proportions of various payment methods for outpatient services during the period from May 2017 to September 2019 were retrospectively analyzed. Also, the patients' satisfaction with the outpatient process was surveyed.

Results: The waiting time for consultation was shortened from 32.25 min to 28.42 min; the consultation time was shortened from 6.52 min to 3.15 min; and the waiting time for payment decreased from 7.40 min to 4.31 min. The proportion of payment via a counter was reduced from 86.80 to 21.79%, the proportion of self-service payment increased from 9.99 to 16.05%, and the proportion of payment during a consultation increased from 3.21 to 61.91%. The scores of the patients' satisfaction with the outpatient services increased from an average of 89.10 points in 2017 to an average of 90.26 points in 2019.

Conclusion: The continuous improvement of the service process markedly increases the efficiency of the outpatient services, and effectively improves patient's satisfaction with the outpatient process, this initiative thus deserves further application.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12913-021-06260-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7986498PMC
March 2021

Detecting de novo mitochondrial mutations in angiosperms with highly divergent evolutionary rates.

Genetics 2021 May;218(1)

Department of Biology, Colorado State University, Fort Collins, CO 80523, USA.

Although plant mitochondrial genomes typically show low rates of sequence evolution, levels of divergence in certain angiosperm lineages suggest anomalously high mitochondrial mutation rates. However, de novo mutations have never been directly analyzed in such lineages. Recent advances in high-fidelity DNA sequencing technologies have enabled detection of mitochondrial mutations when still present at low heteroplasmic frequencies. To date, these approaches have only been performed on a single plant species (Arabidopsis thaliana). Here, we apply a high-fidelity technique (Duplex Sequencing) to multiple angiosperms from the genus Silene, which exhibits extreme heterogeneity in rates of mitochondrial sequence evolution among close relatives. Consistent with phylogenetic evidence, we found that Silene latifolia maintains low mitochondrial variant frequencies that are comparable with previous measurements in Arabidopsis. Silene noctiflora also exhibited low variant frequencies despite high levels of historical sequence divergence, which supports other lines of evidence that this species has reverted to lower mitochondrial mutation rates after a past episode of acceleration. In contrast, S. conica showed much higher variant frequencies in mitochondrial (but not in plastid) DNA, consistent with an ongoing bout of elevated mitochondrial mutation rates. Moreover, we found an altered mutational spectrum in S. conica heavily biased towards AT→GC transitions. We also observed an unusually low number of mitochondrial genome copies per cell in S. conica, potentially pointing to reduced opportunities for homologous recombination to accurately repair mismatches in this species. Overall, these results suggest that historical fluctuations in mutation rates are driving extreme variation in rates of plant mitochondrial sequence evolution.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/genetics/iyab039DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8128415PMC
May 2021

Characteristics and clinical influence factors of arsenic species in plasma and their role of arsenic species as predictors for clinical efficacy in acute promyelocytic leukemia (APL) patients treated with arsenic trioxide.

Expert Rev Clin Pharmacol 2021 Apr 8;14(4):503-512. Epub 2021 Mar 8.

Department of Pharmacy, First Affiliated Hospital of Harbin Medical University, Harbin, China.

: Arsenic trioxide (ATO) is successfully applied to treat acute promyelocytic leukemia (APL). Arsenic species levels in blood are critical to reveal metabolic mechanism and relationship between arsenic species and clinical response. Characteristics and influence factors of arsenic species in APL patients have not been studied.: 305 plasma samples from APL patients treated with ATO were analyzed using HPLC-HG-AFS. Trough concentration (C), distribution, methylation levels of arsenic species were evaluated. The influence factors on arsenic species levels of plasma and association between arsenic concentrations and clinical efficacy were explored.: C of arsenic in effective treatment groups provide basis for defining the target range of arsenic plasma concentrations in APL patients treated with ATO. Distribution trends: DMA > As, MMA> As (p < 0.0001) for continuous slow-rate (CS) infusion and DMA > MMA > As > As (p < 0.0001) for conventional infusion. Infusion methods and combined medication may affect arsenic metabolism. There was a weak correlation between ATO dose and plasma C of arsenic species. C of plasma arsenic species had predictive value for treatment efficacy.: Arsenic concentration monitoring in APL patients treated with ATO is required. These findings are critical to optimize treatment outcomes of ATO therapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/17512433.2021.1893940DOI Listing
April 2021

Differences in the gut microbiomes of dogs and wolves: roles of antibiotics and starch.

BMC Vet Res 2021 Mar 6;17(1):112. Epub 2021 Mar 6.

Institute of Pet Sciences, College of Animal Science and Veterinary Medicine, Shenyang Agricultural University, Shenyang, China.

Background: Dogs are domesticated wolves. Change of living environment, such as diet and veterinary care may affect the gut bacterial flora of dogs. The aim of this study was to assess the gut bacterial diversity and function in dogs compared with captive wolves. We surveyed the gut bacterial diversity of 27 domestic dogs, which were fed commercial dog food, and 31 wolves, which were fed uncooked meat, by 16S rRNA sequencing. In addition, we collected fecal samples from 5 dogs and 5 wolves for shotgun metagenomic sequencing to explore changes in the functions of their gut microbiome.

Results: Differences in the abundance of core bacterial genera were observed between dogs and wolves. Together with shotgun metagenomics, the gut microbiome of dogs was found to be enriched in bacteria resistant to clinical drugs (P < 0.001), while wolves were enriched in bacteria resistant to antibiotics used in livestock (P < 0.001). In addition, a higher abundance of putative α-amylase genes (P < 0.05; P < 0.01) was observed in the dog samples.

Conclusions: Living environment of dogs and domestic wolves has led to increased numbers of bacteria with antibiotic resistance genes, with exposure to antibiotics through direct and indirect methods. In addition, the living environment of dogs has allowed the adaptation of their microbiota to a starch-rich diet. These observations align with a domestic lifestyle for domestic dogs and captive wolves, which might have consequences for public health.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12917-021-02815-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7937242PMC
March 2021

Nanomedicine promotes ferroptosis to inhibit tumour proliferation in vivo.

Redox Biol 2021 06 20;42:101908. Epub 2021 Feb 20.

Department of General Surgery, Geriatrics, Obstetrics and Gynecology, Division of Pulmonary and Critical Care Medicine, Institute of Precision Medicine, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510080, China. Electronic address:

miR-101-3p may play a therapeutic role in various tumours. However, its anti-tumour mechanism remains unclear, and a definitive strategy to treat tumour cells in vivo is lacking. The objective of this study was to investigate the inhibitory mechanism of miR-101-3p on tumour cells and to develop relevant nanomedicines for in vivo therapy. The expression levels of miR-101-3p and its target protein TBLR1 in tumour tissues and cells were detected, and their relationship with ferroptosis was clarified. Furthermore, the efficacy of nanocarriers in achieving in vivo therapeutic gene delivery was evaluated. Nanomedicine was further developed, with the anti-proliferative in vivo therapeutic effect validated using a subcutaneous xenograft cancer model. The expression level of miR-101-3p negatively correlated with clinical tumour size and TNM stage. miR-101-3p restores ferroptosis in tumour cells by directly targeting TBLR1, which in turn promotes apoptosis and inhibits proliferation. We developed nanomedicine that can deliver miR-101-3p to tumour cells in vivo to achieve ferroptosis recovery, as well as to inhibit in vivo tumour proliferation. The miR-101-3p/TBLR1 axis plays an important role in tumour ferroptosis. Nanopharmaceuticals that increase miR-101-3p levels may be effective therapies to inhibit tumour proliferation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.redox.2021.101908DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8113035PMC
June 2021

Characteristics of arsenic species in cerebrospinal fluid (CSF) of acute promyelocytic leukaemia (APL) patients treated with arsenic trioxide plus mannitol.

Br J Clin Pharmacol 2021 Feb 27. Epub 2021 Feb 27.

Department of Pharmacy, First Affiliated Hospital of Harbin Medical University, Harbin, China.

Arsenic speciation in cerebrospinal fluid (CSF) is critical for treatment/prevention of central nervous system (CNS) relapse in acute promyelocytic leukaemia (APL) patients treated with arsenic trioxide (ATO). Previous study showed low total arsenic level in CSF of APL patients. Mannitol infusion was applied to improve blood-brain barrier (BBB) permeability for arsenic. Arsenite (As ), monomethylarsonic acid (MMA ), dimethylarsinic acid (DMA ), and arsenate (As ) in CSF and plasma were analysed by high performance liquid chromatography-hydride generation-atomic fluorescence spectrometry (HPLC-HG-AFS). The profile and concentration of arsenic species in CSF from APL patients administered ATO alone and in combination with mannitol were compared. The overall distribution trend of arsenic species in CSF was As , DMA  > MMA  > As . Arsenicals accumulated in CSF with administration frequency. The permeability of BBB for As was higher than that for MMA and DMA . Arsenic concentration in CSF was much lower than that in plasma. There were significantly higher arsenic species concentrations in CSF of APL patients treated with mannitol than that without mannitol. Mannitol infusion significantly increased As penetration into CSF, which was beneficial to optimize efficacy in APL patients with CNS relapse.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/bcp.14804DOI Listing
February 2021

The bat ACE2 and multiple animal orthologs are functional receptors for bat coronavirus RaTG13 and SARS-CoV-2.

Sci Bull (Beijing) 2021 Jun 19;66(12):1215-1227. Epub 2021 Jan 19.

NHC Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100176, China.

Bat coronavirus (CoV) RaTG13 shares the highest genome sequence identity with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) among all known coronaviruses, and also uses human angiotensin converting enzyme 2 (hACE2) for virus entry. Thus, SARS-CoV-2 is thought to have originated from bat. However, whether SARS-CoV-2 emerged from bats directly or through an intermediate host remains elusive. Here, we found that bat ACE2 (RaACE2) is an entry receptor for both SARS-CoV-2 and RaTG13, although the binding of RaACE2 to the receptor-binding domain (RBD) of SARS-CoV-2 is markedly weaker than that of hACE2. We further evaluated the receptor activities of ACE2s from additional 16 diverse animal species for RaTG13, SARS-CoV, and SARS-CoV-2 in terms of S protein binding, membrane fusion, and pseudovirus entry. We found that the RaTG13 spike (S) protein is significantly less fusogenic than SARS-CoV and SARS-CoV-2, and seven out of sixteen different ACE2s function as entry receptors for all three viruses, indicating that all three viruses might have broad host rages. Of note, RaTG13 S pseudovirions can use mouse, but not pangolin ACE2, for virus entry, whereas SARS-CoV-2 S pseudovirions can use pangolin, but not mouse, ACE2 enter cells efficiently. Mutagenesis analysis revealed that residues 484 and 498 in RaTG13 and SARS-CoV-2 S proteins play critical roles in recognition of mouse and human ACE2s. Finally, two polymorphous bat ACE2s showed different susceptibilities to virus entry by RaTG13 and SARS-CoV-2 S pseudovirions, suggesting possible coevolution. Our results offer better understanding of the mechanism of coronavirus entry, host range, and virus-host coevolution.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.scib.2021.01.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7816560PMC
June 2021

Decoding the RNA viromes in rodent lungs provides new insight into the origin and evolutionary patterns of rodent-borne pathogens in Mainland Southeast Asia.

Microbiome 2021 01 21;9(1):18. Epub 2021 Jan 21.

NHC Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, PR China.

Background: As the largest group of mammalian species, which are also widely distributed all over the world, rodents are the natural reservoirs for many diverse zoonotic viruses. A comprehensive understanding of the core virome of diverse rodents should therefore assist in efforts to reduce the risk of future emergence or re-emergence of rodent-borne zoonotic pathogens.

Results: This study aimed to describe the viral range that could be detected in the lungs of rodents from Mainland Southeast Asia. Lung samples were collected from 3284 rodents and insectivores of the orders Rodentia, Scandentia, and Eulipotyphla in eighteen provinces of Thailand, Lao PDR, and Cambodia throughout 2006-2018. Meta-transcriptomic analysis was used to outline the unique spectral characteristics of the mammalian viruses within these lungs and the ecological and genetic imprints of the novel viruses. Many mammalian- or arthropod-related viruses from distinct evolutionary lineages were reported for the first time in these species, and viruses related to known pathogens were characterized for their genomic and evolutionary characteristics, host species, and locations.

Conclusions: These results expand our understanding of the core viromes of rodents and insectivores from Mainland Southeast Asia and suggest that a high diversity of viruses remains to be found in rodent species of this area. These findings, combined with our previous virome data from China, increase our knowledge of the viral community in wildlife and arthropod vectors in emerging disease hotspots of East and Southeast Asia. Video abstract.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s40168-020-00965-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7818139PMC
January 2021

Low-dose decitabine priming endows CAR T cells with enhanced and persistent antitumour potential via epigenetic reprogramming.

Nat Commun 2021 01 18;12(1):409. Epub 2021 Jan 18.

Department of Molecular Biology and Immunology, Institute of Basic Medicine, Chinese People's Liberation Army General Hospital, Beijing, China.

Insufficient eradication capacity and dysfunction are common occurrences in T cells that characterize cancer immunotherapy failure. De novo DNA methylation promotes T cell exhaustion, whereas methylation inhibition enhances T cell rejuvenation in vivo. Decitabine, a DNA methyltransferase inhibitor approved for clinical use, may provide a means of modifying exhaustion-associated DNA methylation programmes. Herein, anti-tumour activities, cytokine production, and proliferation are enhanced in decitabine-treated chimeric antigen receptor T (dCAR T) cells both in vitro and in vivo. Additionally, dCAR T cells can eradicate bulky tumours at a low-dose and establish effective recall responses upon tumour rechallenge. Antigen-expressing tumour cells trigger higher expression levels of memory-, proliferation- and cytokine production-associated genes in dCAR T cells. Tumour-infiltrating dCAR T cells retain a relatively high expression of memory-related genes and low expression of exhaustion-related genes in vivo. In vitro administration of decitabine may represent an option for the generation of CAR T cells with improved anti-tumour properties.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41467-020-20696-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7814040PMC
January 2021

Retracted: Naturally Occurring Sesquiterpene Lactone-Santonin, Exerts Anticancer Effects in Multi-Drug Resistant Breast Cancer Cells by Inducing Mitochondrial Mediated Apoptosis, Caspase Activation, Cell Cycle Arrest, and by Targeting Ras/Raf/MEK/ERK Signaling Pathway.

Med Sci Monit 2020 12 30;26:e930755. Epub 2020 Dec 30.

Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China (mainland).

It is now clear that the photomicrographs in Figure 2 are duplicates of the same image and that Figures 4 and 5 have been 'copied' from a publication "Lupeol triterpene exhibits potent antitumor effects in A427 human lung carcinoma cells via mitochondrial mediated apoptosis, ROS generation, loss of mitochondrial membrane potential and downregulation of m-TOR/PI3Ksol;AKT signalling pathway" by Wei He, Xiang Li, Shuyue Xia, PMID: 30003730. Because the manuscript contains non-credible results and has also breached copyright, this journal is retracting the above publication.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.12659/MSM.930755DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7781048PMC
December 2020

Case Report: Low-Dose Decitabine Plus Anti-PD-1 Inhibitor Camrelizumab for Previously Treated Advanced Metastatic Non-Small Cell Lung Cancer.

Front Oncol 2020 22;10:558572. Epub 2020 Oct 22.

School of Medicine, Nankai University, Tianjin, China.

Although the programmed death 1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitors have markedly changed the strategies of cancer treatment, most patients with advanced non-small cell lung cancer (NSCLC) do not respond to PD-1/PD-L1 monotherapy. Epigenetic drugs have been hypothesized to possess the potential to sensitize PD-1/PD-L1 inhibitors. Three patients with advanced metastatic NSCLC failed to respond to first-line systemic therapy and had a low tumor mutation burden, low tumor neoantigen burden, low microsatellite instability, and HLA loss of heterozygosity according to their target lesion biopsies, all of which were considered unfavorable factors for PD-1/PD-L1 blockage. However, all three patients responded to low-dose decitabine, an epigenetic drug, in combination with camrelizumab (anti-PD-1 antibody), with only controllable adverse events, indicating that low-dose decitabine can sensitize PD-1/PD-L1 inhibitors. We report a novel therapy with low-dose decitabine plus camrelizumab for advanced NSCLC on the basis of successful treatment of three patients, emphasizing the potential of epigenetic drugs to regulate PD-1/PD-L1 inhibitors in advanced NSCLC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fonc.2020.558572DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7649792PMC
October 2020

Corrigendum: Identification of Diverse Bat Alphacoronaviruses and Betacoronaviruses in China Provides New Insights Into the Evolution and Origin of Coronavirus-Related Diseases.

Front Microbiol 2020 26;11:597510. Epub 2020 Oct 26.

NHC Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

[This corrects the article DOI: 10.3389/fmicb.2019.01900.].
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fmicb.2020.597510DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7649633PMC
October 2020

Trifolium Flavonoids Overcome Gefitinib Resistance of Non-Small-Cell Lung Cancer Cell by Suppressing ERK and STAT3 Signaling Pathways.

Biomed Res Int 2020 22;2020:2491304. Epub 2020 Oct 22.

Jinhua Municipal Central Hospital, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, China.

Gefitinib is a tyrosine kinase inhibitor of EGFR (epidermal growth factor receptor) and represents the first-line treatment for EGFR mutation patients with NSCLC (non-small-cell lung cancer) therapeutics. However, NSCLC patients are inclined to develop acquired gefitinib drug resistance through nowadays, unarticulated mechanisms of chemoresistance. Here, we investigated the role of TF (Trifolium flavonoids) on sensitizing gefitinib resistance in NSCLC cells and revealed its potential mechanism of action. We demonstrated that TF exerted significantly potential chemosensitivity in gefitinib resistant NSCLC cells. MTT assay and cytological methods were used to analyze cell viability and apoptosis in NSCLC cell line PC-9R. Both TF and gefitinib suppressed PC-9R cell growth in a dose-dependent manner. Subtoxic concentrations of TF did significantly augment gefitinib-induced apoptosis in PC-9R cell line. The TF promoted chemosensitivity was major mediated by the PARP and caspases activation. Meanwhile, the TF promoted chemosensitivity also decreased the expression of Bcl-2 and Mcl-1. Finally, TF significantly reduced the phosphorylation levels of STAT3 and ERK. Altogether, the results of the present study indicated the potential mechanisms of chemosensitivity of TF in gefitinib-induced apoptosis of NSCLC by downregulating ERK and STAT3 signaling pathways and Bcl2 and Mcl-1 expression and a promising application of TF in therapy of NSCLC with gefitinib resistant.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2020/2491304DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7603574PMC
May 2021

Efficacy and Safety of Transarterial Chemoembolization Combined With Anlotinib for Unresectable Hepatocellular Carcinoma: A Retrospective Study.

Technol Cancer Res Treat 2020 Jan-Dec;19:1533033820965587

The First Affiliated Hospital of Sun Yat-sen University, Guangdong, China.

Objective: This study aimed to explore the efficacy and safety of using transarterial chemoembolization (TACE) combined with anlotinib in patients with unresectable hepatocellular carcinoma, compared with TACE alone.

Methods: This was a single-center study, retrospectively recruited 82 unresectable HCC patients who received either TACE alone (TA group; n = 46) or TACE combined with anlotinib (TC group; n = 36) between Jan 2018 and Jan 2019. The primary outcomes were progression-free survival (PFS) and overall survival (OS). While the secondary outcomes were the objective response rate (ORR), the disease control rate (DCR), and main complications. Log-rank test and Kaplan-Meier method was used to calculate the survival difference. All statistical tests were 2-sided and P value <0.05 were taken as statistically significant.

Results: Patients in TC group had a significant higher PFS than those in TA group (7.35 months vs. 5.54 months, p = 0.035). Although 3-month survival rate in the 2 groups was not statistically different (97.2% vs. 93.5%, p = 0.627), the survival rate at 6 months and 1 year were strongly higher in TC group (83.3% vs. 56.5%, p = 0.016; 66.7% vs. 19.6%, respectively, p < 0.05). Furthermore, there was a significantly higher ORR in TC group, while no statistical difference existed in DCR. Neither treatment-related mortality nor grade 4 adverse events (AEs) occurred. However, 2 patients in TC group had grade 3 AEs (one suffered with erythra, and the other with hand-foot-skin reaction), which disappeared after prompt treatment.

Conclusion: TACE combined with anlotinib is safe and may improve outcomes for unresectable HCC patients comparing with TACE alone. Randomized controlled trials are warranted to further evaluate treatment effects of anlotinib in HCC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/1533033820965587DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7586029PMC
October 2020

Impact of Age on the Efficacy of Immune Checkpoint Inhibitor-Based Combination Therapy for Non-small-Cell Lung Cancer: A Systematic Review and Meta-Analysis.

Front Oncol 2020 23;10:1671. Epub 2020 Sep 23.

Department of Bio-Therapeutic, The First Medical Center, Chinese People's Liberation Army General Hospital, Beijing, China.

Despite the acknowledged benefits of immune checkpoint inhibitor (ICI)-based combination therapy (either with other checkpoint inhibitors, chemotherapy, targeted therapy, or radiotherapy), little is known about the impact of age on the efficacy of ICI -based combination therapy in non-small-cell lung cancer (NSCLC) patients. We conducted a systematic review and meta-analysis to investigate the differences in the benefits of ICI-based combination therapy for NSCLC by age (cut-off age, 65 years). We systematically searched randomized controlled trials (RCTs) of ICI plus other therapies including other ICIs, chemotherapies, targeted therapies, or radiotherapies, in the PubMed, Embase, and Cochrane databases with available hazard ratios (HRs) and 95% confidence intervals (CIs) for death and disease progression according to patient age. The search deadline was May 25, 2020. First, we calculated the pooled HRs of younger and older patients based on the HRs from each trial. Second, we assessed the pooled ratio of HRs reported in older patients to the HRs reported in younger patients for progression or death by the random-effects model. An estimated pooled HR ratio was lower than 1 indicating a better effect in older patients and higher than 1 indicating a better effect in younger patients. A total of 10 eligible RCTs were included in our meta-analysis. The pooled HR for overall survival (OS) comparing ICI combined with other therapies to non-ICI regimens was 0.67 (95%CI 0.58-0.78) for younger patients and 0.79 (95%CI 0.70-0.90) for older patients. The pooled HRs ratio for OS reported in older patients compared to younger patients was 1.16 (95%CI 0.99-1.34), indicating no statistically significant difference between younger and older patients. Consistent with the findings related to OS, the analysis also demonstrated that ICI-based immunotherapy could significantly prolong progression-free survival (PFS) in younger and older patients (HR = 0.55; 95% CI 0.47-0.66, and HR = 0.64; 95% CI 0.57-0.71). The same results could also be observed in the pooled HRs ratio for PFS (HR = 1.15, 95%CI 0.91-1.46) indicating comparable efficacy of ICI-based combination therapy in younger and older patients with NSCLC. ICI-based combination therapy vs. non-ICI treatment had comparable efficacy in younger and older NSCLC patients with a cut-off age of 65 years.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fonc.2020.01671DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7538697PMC
September 2020

Novel serological biomarkers for inflammation in predicting disease severity in patients with COVID-19.

Int Immunopharmacol 2020 Dec 3;89(Pt A):107065. Epub 2020 Oct 3.

Department of Clinical Laboratory, The First Affiliated Hospital of Nanchang University, Nanchang 330000, China. Electronic address:

Background: Patients with severe coronavirus disease 2019 (COVID-19) develop acute respiratory distress and multi-system organ failure and are associated with poor prognosis and high mortality. Thus, there is an urgent need to identify early diagnostic and prognostic biomarkers to determine the risk of developing serious illness.

Methods: We retrospectively analyzed 114 patients with COVID-19 at the Jinyintan Hospital, Wuhan based on their clinical and laboratory data. Patients were categorized into severe and mild to moderate disease groups. We analyzed the potential of serological inflammation indicators in predicting the severity of COVID-19 in patients using univariate and multivariate logistic regression, receiver operating characteristic curves, and nomogram analysis. The Spearman method was used to understand the correlation between the serological biomarkers and duration of hospital stay.

Results: Patients with severe disease had reduced neutrophils and lymphocytes; severe coagulation dysfunction; altered content of biochemical factors (such as urea, lactate dehydrogenase); elevated high sensitivity C-reactive protein levels, neutrophil-lymphocyte, platelet-lymphocyte, and derived neutrophil-lymphocyte ratios, high sensitivity C-reactive protein-prealbumin ratio (HsCPAR), systemic immune-inflammation index, and high sensitivity C-reactive protein-albumin ratio (HsCAR); and low lymphocyte-monocyte ratio, prognostic nutritional index (PNI), and albumin-to-fibrinogen ratio. PNI, HsCAR, and HsCPAR correlated with the risk of severe disease. The nomogram combining the three parameters showed good discrimination with a C-index of 0.873 and reliable calibration. Moreover, HsCAR and HsCPAR correlated with duration of hospital stay.

Conclusion: Taken together, PNI, HsCAR, and HsCPAR may serve as accurate biomarkers for the prediction of disease severity in patients with COVID-19 upon admission/hospitalization.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.intimp.2020.107065DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7532789PMC
December 2020

Determinants of pain in advanced HCC patients recieving hepatic artery infusion chemotherapy.

Invest New Drugs 2021 Apr 1;39(2):394-399. Epub 2020 Oct 1.

Department of Interventional Radiology, the First Affiliated Hospital of Sun Yat-Sen University, No. 58 Zhongshan 2 Road, Guangzhou, 510080, China.

Purpose Hepatic arterial infusion chemotherapy (HAIC) is one of the options to treat unresectable hepatocellular carcinoma (HCC). The majority of HCC patients suffer great pain in the course of HAIC treatment. To improve the quality of life and the efficacy of HAIC treatment, the causes of pain, the choice of an analgesic regimen, and the relationship between pain and prognosis of HCC were analyzed. Methods A total of 376 HCC patients under HAIC in our hospital were recriuted between March 2017 and September 2019. Multivariate linear regression analysis (stepwise) was used to calculate the potential factors related to the severe pain in HCC patients under HAIC. Analgesics treatments were carried out based on the results of the visual analogue scale (VAS) score which was used to evaluate the pain. Results The mean value of the VAS score is 3.604, which indicates that the pain in most patients is mild and endurable. Intra-arterial lidocaine injection is an effective method in most patients (96%, 361 of 376), and the total score of VAS is reduced from 1355 to 195 following lidocaine injection. Multivariate analysis suggestes that oxaliplatin (OXA) preparation time, hepatic artery diameter and OXA manufacturers (R = 0.859) are influential factors for pain scores. Conclusion This study demonstrates an effective way to systematically assess and ease pain in HCC patients with HAIC treatment. OXA preparation time, hepatic artery diameter, and OXA manufacturers are the potential influencing factors for pain. This work presented here will provide a detailed understanding of the clinical application of HAIC in advanced HCC patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10637-020-01009-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7960585PMC
April 2021

Clinical development of CAR T cell therapy in China: 2020 update.

Cell Mol Immunol 2021 Apr 30;18(4):792-804. Epub 2020 Sep 30.

Department of Bio-Therapeutic, The First Medical Center, Chinese PLA General Hospital, Beijing, 100853, China.

Chimeric antigen receptor (CAR) T-cell therapy has achieved significant success in the treatment of hematological malignancies. In recent years, fast-growing CAR T clinical trials have actively explored their potential application scenarios. According to the data from the clinicaltrials.gov website, China became the country with the most registered CAR T trials in September 2017. As of June 30, 2020, the number of registered CAR T trials in China has reached 357. In addition, as many as 150 other CAR T trials have been registered on ChiCTR. Although CAR T therapy is flourishing in China, there are still some problems that cannot be ignored. In this review, we aim to systematically summarize the clinical practice of CAR T-cell therapy in China. This review will provide an informative reference for colleagues in the field, and a better understanding of the history and current situation will help us more reasonably conduct research and promote cooperation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41423-020-00555-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8115146PMC
April 2021

Occurrence, distribution, and health risk assessment of quinolone antibiotics in water, sediment, and fish species of Qingshitan reservoir, South China.

Sci Rep 2020 09 25;10(1):15777. Epub 2020 Sep 25.

Department of Applied Ecology, Faculty of Environmental Sciences, Czech University of Life Sciences Prague, Kamýcká 129, 16500, Prague, Czech Republic.

The residual antibiotics in the environment have lately caused widespread concerns. However, little information is available on the antibiotic bioaccumulation and its health risk in drinking water resources of South China. Therefore, the occurrence, distribution, and health risk of four quinolone antibiotics including ofloxacin (OFX), norfloxacin (NOR), ciprofloxacin (CIP), and enrofloxacin (ENR) in the Qingshitan reservoir using high-performance liquid chromatography were investigated. Results revealed that the concentrations in water, sediment, and edible fish ranged from 3.49-660.13 ng/L, 1.03-722.18 μg/kg, and 6.73-968.66 μg/kg, respectively. The ecological risk assessment via the risk quotient (RQ) method showed that the values in sediment were all greater than 1, posing a high risk to the environment. The health risk index of water samples was at the maximum acceptable level, with OFX at the top while the rest were at the medium risk level. The main edible fish kinds of the reservoir had high dietary safety and the highest contaminations were found in carnivorous feeding habits and demersal habitat fishes with OFX as the highest magnitude. Source identification and correlation analysis using SPSS showed significant relationships between NOR with pH and turbidity (in water), as well as total phosphor (TP) and total organic carbon (TOC) in sediment. NOR was the highest in sediment which mostly sourced from livestock wastewater, croplands irrigation drain water, and stormwater. Correlations between CIP and ENR with TP were significant, while OFX was positively associated with total nitrogen (TN) which mainly originated from urban sewage as well as directly dosed drugs in fish farms. In conclusion, our results are of great significance for ensuring the safety of drinking water and aquatic products in this region.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-020-72324-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7519050PMC
September 2020

Staprexanthones, Xanthone-Type Stimulators of Pancreatic β-Cell Proliferation from a Mangrove Endophytic Fungus.

J Nat Prod 2020 10 23;83(10):2996-3003. Epub 2020 Sep 23.

Key Laboratory of Marine Drugs, Chinese Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, People's Republic of China.

This project was focused on the discovery of novel compounds that promote endogenous β-cell regeneration. Screening of extracts identified the fungus as a promising candidate. After fermentation and extraction of , we isolated five new prenylated xanthones, namely, staprexanthones A-E (-), with staprexanthone A () being the first natural xanthone bearing a rare 4,5-dimethyl-1,3-dioxolane moiety. Compounds , , and significantly increased β-cell numbers in a zebrafish model. Further analysis revealed that and promoted β-cell mass expansion by increasing proliferation of existing β-cells though promotion of cell-cycle progression at the G1/S transition. These findings indicate that prenylated xanthones are potential new drug leads for antidiabetes therapy by stimulating β-cell regeneration.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.jnatprod.0c00535DOI Listing
October 2020

Spatial distribution, source identification, and risk assessment of organochlorines in wild tilapia from Guangxi, South China.

Sci Rep 2020 09 16;10(1):15179. Epub 2020 Sep 16.

School of Marine Sciences, Guangxi University, Nanning, 530004, China.

Seventy-five wild tilapia samples from six rivers (ten sites) in Guangxi province were collected and analyzed for 53 organochlorine compounds. DDTs, endosulfan, and PCBs were the most dominant compounds found in this study. Tiandong County (TD) and Guigang City (GG) sites were found to be heavily contaminated with high levels of endosulfan (385-925 ng/g lw) and/or DDTs (20.1-422 ng/g lw). The diagnostic ratios indicated that the residues of DDTs and endosulfan in wild tilapia are associated with historical applications as well as the recent introduction of technical DDTs and endosulfan at some sampling sites. The correlation between total length, body mass, and organochlorines (OCs) was higher than the correlation between age and lipid content. There was no significant correlation between organochlorine pesticides (OCPs) and lipid content. Therefore, for organisms, the feeding intensity (related to length and mass) of fish could better reflect degree of pollution than exposure time (age) of fish. The hazardous ratios for the 50th and 95th percentile data of OCPs and PCBs in fish were both below 1, suggesting that daily exposure to OCPs and PCBs yields a lifetime cancer risk lower than 1 in 10,000.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-020-72160-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7495417PMC
September 2020

2020 taxonomic update for phylum Negarnaviricota (Riboviria: Orthornavirae), including the large orders Bunyavirales and Mononegavirales.

Arch Virol 2020 Dec 4;165(12):3023-3072. Epub 2020 Sep 4.

Colorado State University, Fort Collins, CO, USA.

In March 2020, following the annual International Committee on Taxonomy of Viruses (ICTV) ratification vote on newly proposed taxa, the phylum Negarnaviricota was amended and emended. At the genus rank, 20 new genera were added, two were deleted, one was moved, and three were renamed. At the species rank, 160 species were added, four were deleted, ten were moved and renamed, and 30 species were renamed. This article presents the updated taxonomy of Negarnaviricota as now accepted by the ICTV.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00705-020-04731-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7606449PMC
December 2020

Lanostane inhibits the proliferation and bone metastasis of human breast cancer cells via inhibition of Rho-associated kinase signaling.

J BUON 2020 May-Jun;25(3):1323-1329

Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.

Purpose: This study was performed to investigate the effects of lanostane against human breast cancer cells with emphasis on its potential to inhibit cancer cell growth and metastasis along with understanding the underlying molecular mechanism mediating the effects.

Methods: The SK-BR-3 normal breast line and the MB-157 breast cancer cell line were used in this study. MTT of cell growth was used to determine the viability of cells under lanostane treatment. Colony formation assay was used to analyze the clone forming capability of cancer cells when treated with lanostane. DAPI and acridine orange (AO)/ethidium bromide (EB) staining assays were performed for assessing the apoptic cell death. The level of cellular apoptosis was further examined using flow cytometry. Wound healing and transwell assays were performed to determine the migration and invasion of cancer cells. Western blotting was used for determining the concentration of proteins of interest.

Results: The lanostane treatment of cancer cells resulted in loss of cell viability. The IC50 value was 15µM and the inhibitory effects were dose-dependent. However, the inhibition of cell proliferation in normal breast cells was comparatively lower. The antiproliferative effects of lanostane were modulated through Bax/Bcl-2 pathway inducing apoptosis of cancer cells. Furthermore, the lanostane rendered cancer cells less motile and reduced their metastasis remarkably. The inhibition of cell metastasis was modulated through Rho-associated kinases (ROCK) signaling pathway which is involved in metastasis of breast cancer to bone tissues. Hence, the results suggested that lanostane inhibited the breast cancer metastasis to bone.

Conclusion: The results of the present study are suggestive of anticancer effects of lanostene triterpene which exerted its effects by inhibiting cell proliferation and metastasis of breast cancer cells mediated through inactivation of Rho-associated kinase signaling. The study holds promise to provide a lead for exploring the secondary metabolite-based anticancer approach against various human malignancies.
View Article and Find Full Text PDF

Download full-text PDF

Source
February 2021

Karyotypic Evolution of Sauropsid Vertebrates Illuminated by Optical and Physical Mapping of the Painted Turtle and Slider Turtle Genomes.

Genes (Basel) 2020 08 12;11(8). Epub 2020 Aug 12.

Department of Ecology, Evolution, and Organismal Biology, Iowa State University, Ames, IA 50011, USA.

Recent sequencing and software enhancements have advanced our understanding of the evolution of genomic structure and function, especially addressing novel evolutionary biology questions. Yet fragmentary turtle genome assemblies remain a challenge to fully decipher the genetic architecture of adaptive evolution. Here, we use optical mapping to improve the contiguity of the painted turtle () genome assembly and use fluorescent in situ hybridization (FISH) of bacterial artificial chromosome (BAC) clones, BAC-FISH, to physically map the genomes of the painted and slider turtles (). Optical mapping increased 's N50 by ~242% compared to the previous assembly. Physical mapping permitted anchoring ~45% of the genome assembly, spanning 5544 genes (including 20 genes related to the sex determination network of turtles and vertebrates). BAC-FISH data revealed assembly errors in and assemblies, highlighting the importance of molecular cytogenetic data to complement bioinformatic approaches. We also compared 's anchored scaffolds to the genomes of other chelonians, chicken, lizards, and snake. Results revealed a mostly one-to-one correspondence between chromosomes of painted and slider turtles, and high homology among large syntenic blocks shared with other turtles and sauropsids. Yet, numerous chromosomal rearrangements were also evident across chelonians, between turtles and squamates, and between avian and non-avian reptiles.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/genes11080928DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7464131PMC
August 2020

Programming CAR T cells to enhance anti-tumor efficacy through remodeling of the immune system.

Front Med 2020 Dec 13;14(6):726-745. Epub 2020 Aug 13.

Molecular & Immunological Department, Bio-therapeutic Department, Chinese PLA General Hospital, Beijing, 100853, China.

Chimeric antigen receptor (CAR) T cells have been indicated effective in treating B cell acute lymphoblastic leukemia and non-Hodgkin lymphoma and have shown encouraging results in preclinical and clinical studies. However, CAR T cells have achieved minimal success against solid malignancies because of the additional obstacles of their insufficient migration into tumors and poor amplification and persistence, in addition to antigen-negative relapse and an immunosuppressive microenvironment. Various preclinical studies are exploring strategies to overcome the above challenges. Mobilization of endogenous immune cells is also necessary for CAR T cells to obtain their optimal therapeutic effect given the importance of the innate immune responses in the elimination of malignant tumors. In this review, we focus on the recent advances in the engineering of CAR T cell therapies to restore the immune response in solid malignancies, especially with CAR T cells acting as cellular carriers to deliver immunomodulators to tumors to mobilize the endogenous immune response. We also explored the sensitizing effects of conventional treatment approaches, such as chemotherapy and radiotherapy, on CAR T cell therapy. Finally, we discuss the combination of CAR T cells with biomaterials or oncolytic viruses to enhance the anti-tumor outcomes of CAR T cell therapies in solid tumors.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11684-020-0746-0DOI Listing
December 2020