Publications by authors named "Xin Huang"

2,126 Publications

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Chronic Urticaria: Advances in Understanding of the Disease and Clinical Management.

Clin Rev Allergy Immunol 2021 Sep 16. Epub 2021 Sep 16.

Department of Dermatology, Hunan Key Laboratory of Medical Epigenomics, The Second Xiangya Hospital of Central South University, 139 Middle Renmin Road, Hunan, 410011, Changsha, China.

Chronic urticaria (CU) is a common skin condition characterized by the recurrence of wheals, with or without angioedema, which lasts for at least 6 weeks. Owing to its pruritus and incurability, this disease adversely affects the patients' physical and mental health and diminishes the quality of life. CU is generally classified into two subtypes based on the relevance of eliciting factors: chronic spontaneous urticaria (CSU) and chronic inducible urticaria (CIndU), the latter of which is further divided into several subtypes. To improve the understanding and clinical management of this highly heterogeneous disorder, the EAACI/GALEN/EDF/WAO guideline was developed and published in 2018 based on evidence and expert consensus. The diagnostic and treatment algorithms proposed by the guideline have largely facilitated dermatologists in clinical practice. However, several questions remained unsolved and have been widely investigated in the recent years. First, a better understanding of the association between chronic urticaria and its potential underlying causes or eliciting factors such as autoimmunity, infections, coagulation aberrance, and vitamin D deficiency is warranted. This would lead to updates in the diagnostic and treatment procedures of different subtypes of chronic urticaria. Secondly, treatment for recalcitrant cases, especially those resistant to or intolerant of second-generation antihistamines and (or) omalizumab, calls for novel therapeutic measures or strategies. In the present review, we summarized recent advances in the understanding and management of both CSU and CIndU, with special emphasis on their underlying causes or eliciting factors, pathogenic mechanisms, potential targets for intervention, and advances in treatment strategies.
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http://dx.doi.org/10.1007/s12016-021-08886-xDOI Listing
September 2021

Recyclable fluorous cinchona organocatalysts for asymmetric synthesis of biologically interesting compounds.

Authors:
Xin Huang Wei Zhang

Chem Commun (Camb) 2021 Sep 15. Epub 2021 Sep 15.

Department of Chemistry, University of Massachusetts, 100 Morrissey Boulevard, Boston, MA 02125, USA.

Organocatalysis has unique modes of activation, mild reaction conditions, and good catalyst structural amenability. The integration of green techniques such as catalyst recovery and one-pot reactions makes organocatalysis more efficient and attractive. Presented in this article are the recyclable cinchona alkaloid-catalyzed reactions including fluorination and Michael addition-initiated cascade reactions in asymmetric synthesis of functionalized compounds of biological interest.
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http://dx.doi.org/10.1039/d1cc03722fDOI Listing
September 2021

Betulinic acid promotes the osteogenic differentiation of human periodontal ligament stem cells by upregulating EGR1.

Acta Biochim Biophys Sin (Shanghai) 2021 Sep 13. Epub 2021 Sep 13.

Department of Stomatology, Jing'an District Institute of Dantal Diseases, Shanghai 200040, China.

Periodontitis is one of the most common chronic inflammations of the oral cavity, which eventually leads to tooth loss. Betulinic acid (BetA) is an organic acid that has anti-inflammatory effects and is derived from fruits and plants, but its effect on the osteogenic differentiation of human periodontal ligament stem cells (hPDLSCs) is still unclear. This study aimed to explore the effect of BetA on the osteogenic differentiation of hPDLSCs and its mechanism. Our results revealed that BetA not only promoted the viability of hPDLSCs but also induced their osteogenic differentiation in a dose-dependent manner. In addition, RNA sequencing was used to screen the differentially expressed genes (DEGs) after hPDLSCs were treated with BetA, and 127 upregulated and 138 downregulated genes were identified. Gene Ontology enrichment analysis showed that DEGs were mainly involved in the response to lithium ions and the positive regulation of macrophage-derived foam cell differentiation. The Kyoto Encyclopedia of Genes and Genomes analysis results revealed that DEGs were enriched in the nuclear factor-κB and interleukin-17 signaling pathways. More importantly, we confirmed that early growth response gene 1 (EGR1), one of the three DEGs involved in bone formation, significantly promoted the expression of osteogenic markers and the mineralization of hPDLSCs. Knockdown of EGR1 obviously limited the effect of BetA on the osteogenic differentiation of hPDLSCs. In conclusion, BetA promoted the osteogenic differentiation of hPDLSCs through upregulating EGR1, and BetA might be a promising candidate in the clinical application of periodontal tissue regeneration.
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http://dx.doi.org/10.1093/abbs/gmab111DOI Listing
September 2021

Change of extreme snow events shaped the roof of traditional Chinese architecture in the past millennium.

Sci Adv 2021 Sep 8;7(37):eabh2601. Epub 2021 Sep 8.

School of Atmospheric Sciences, Nanjing University, Nanjing 210023, China.

[Figure: see text].
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http://dx.doi.org/10.1126/sciadv.abh2601DOI Listing
September 2021

A nine-hub-gene signature of metabolic syndrome identified using machine learning algorithms and integrated bioinformatics.

Bioengineered 2021 Dec;12(1):5727-5738

Department of Cardiovascular Medicine, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.

Early risk assessments and interventions for metabolic syndrome (MetS) are limited because of a lack of effective biomarkers. In the present study, several candidate genes were selected as a blood-based transcriptomic signature for MetS. We collected so far the largest MetS-associated peripheral blood high-throughput transcriptomics data and put forward a novel feature selection strategy by combining weighted gene co-expression network analysis, protein-protein interaction network analysis, LASSO regression and random forest approaches. Two gene modules and 51 hub genes as well as a 9-hub-gene signature associated with metabolic syndrome were identified. Then, based on this 9-hub-gene signature, we performed logistic analysis and subsequently established a web nomogram calculator for metabolic syndrome risk (https://xjtulgz.shinyapps.io/DynNomapp/). This 9-hub-gene signature showed excellent classification and calibration performance (AUC = 0.968 in training set, AUC = 0.883 in internal validation set, AUC = 0.861 in external validation set) as well as ideal potential clinical benefit.
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http://dx.doi.org/10.1080/21655979.2021.1968249DOI Listing
December 2021

Pancreatic cancer-derived exosomal microRNA-19a induces β-cell dysfunction by targeting ADCY1 and EPAC2.

Int J Biol Sci 2021 21;17(13):3622-3633. Epub 2021 Aug 21.

Department of Gastroenterology, Shanghai Jiaotong University School of Medicine affiliating Shanghai 9th People's Hospital, Shanghai, China.

New-onset diabetes mellitus has a rough correlation with pancreatic cancer (PaC), but the underlying mechanism remains unclear. This study aimed to explore the exosomal microRNAs and their potential role in PaC-induced β-cell dysfunction. The pancreatic β cells were treated with isolated exosomes from PaC cell lines, SW1990 and BxPC-3, before measuring the glucose-stimulated insulin secretion (GSIS), validating that SW1990 and BxPC-3 might disrupt GSIS of both β cell line MIN6 and primary mouse pancreatic islets. The difference in expression profiles between exosomes and exosome-free medium of PaC cell lines was further defined, revealing that miR-19a secreted by PaC cells might be an important signaling molecule in this process. Furthermore, adenylyl cyclase 1 (Adcy1) and exchange protein directly activated by cAMP 2 (Epac2) were verified as the direct targets of exogenous miR-19a, which was involved in insulin secretion. These results indicated that exosomes might be an important mediator in the pathogenesis of PaC-DM, and miR-19a might be the effector molecule. The findings shed light on the pathogenesis of PaC-DM.
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http://dx.doi.org/10.7150/ijbs.56271DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8416731PMC
August 2021

Reconstruction of Large Cervicofacial Defects With Expanded Island Superficial Temporal Artery Flaps and an 810-nm Diode Laser Hair Removal Technique: A Retrospective Study.

Ann Plast Surg 2021 Sep 10. Epub 2021 Sep 10.

From the Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China.

Background: Extensive cervicofacial reconstruction is challenging for plastic surgeons. Because of the location of the adjacent scalp flap nourished by the superficial temporal artery (STA), it can be a candidate for cervicofacial reconstruction.

Objectives: This article aims to report a combined treatment of an expanded island STA flap and an 810-nm diode laser hair removal technique for extensive cervicofacial defects.

Methods: Between January 2015 and December 2018, 10 patients with lower face and neck scar contraction were reconstructed with a bilateral or unilateral expanded STA island flap and an 810-nm diode laser for hair removal in this retrospective study. Hair removal via the 810-nm laser was started when the injected volume reached the volume of the expander, with a fluence of 35 to 40 J/cm2 and a 1 to 2 Hz repetition rate. Before second-stage surgery, the hair reduction rate was assessed. Twelve months after surgery, the degree of epilation efficacy according to the satisfaction scale and Global Aesthetic Improvement Scale was evaluated.

Results: This study included 2 single-pedicle flaps and 8 double-pedicle flaps. The average size of the implanted expanders was 600 mL. The average injected volume was 1405 mL. Before second surgery, there was a 67.4% hair reduction rate. Twelve months after surgery, the results of Global Aesthetic Improvement Scale were very good (3), good (6), average (1), and poor (0).

Conclusions: The expanded island STA flap and 810-nm diode laser technique may be a novel treatment option for severe face and neck aesthetic reconstruction.
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http://dx.doi.org/10.1097/SAP.0000000000002985DOI Listing
September 2021

Symptom structure of posttraumatic stress disorder after parental bereavement - a network analysis of Chinese parents who have lost their only child.

J Affect Disord 2021 Sep 2;295:673-680. Epub 2021 Sep 2.

CAS Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing 100101, China; Department of Psychology, University of Chinese Academy of Sciences, Beijing 100049, China. Electronic address:

Background: The death of a child is a highly traumatic event and often leads to mental health problems, including posttraumatic stress disorder (PTSD). Previous studies have focused on overall PTSD after the loss of an only child; however, little attention has been given to PTSD at the symptom level. This study aims to identify the network structure of PTSD symptoms in bereaved parents who have lost their only child, known as Shidu parents in Chinese society.

Methods: A cross-sectional study enrolled 385 bereaved individuals who had lost an only child across 10 cities in China from November 2016 to July 2017. PTSD symptoms were measured by the PTSD Checklist for DSM-5 (PCL-5). Network analysis was implemented by using the R packages qgraph and bootnet.

Results: The PTSD network revealed that diminished interest, exaggerated startle, irritability/anger, and nightmares were the most central symptoms. The strongest connections emerged between the symptoms of recurrent thoughts and nightmares, irritability/anger and reckless/self-destructive behavior, and hypervigilance and exaggerated startle.

Limitations: We utilized cross-sectional data, and it is therefore not possible to infer the evolution of the symptom network over time. In addition, participants were limited to parents who had lost an only child, and the findings of this study must be interpreted with caution.

Conclusions: The current study provides further clarity regarding how PTSD symptoms relate to each other in bereaved parents who have lost an only child. Symptoms with high centrality and connectedness may be viable targets for intervention in bereaved parents who have lost an only child.
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http://dx.doi.org/10.1016/j.jad.2021.08.123DOI Listing
September 2021

Genomic characterization and outcome evaluation of kinome fusions in lung cancer revealed novel druggable fusions.

NPJ Precis Oncol 2021 Sep 10;5(1):81. Epub 2021 Sep 10.

Bone Metastasis Service, Department of Orthopaedics, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.

Kinase fusions represent an important type of somatic alterations that promote oncogenesis and serve as diagnostic markers in lung cancer. We aimed to identify the landscape of clinically relevant kinase fusions in Chinese lung cancer and to explore rare kinase rearrangements; thus, providing valuable evidence for therapeutic decision making. We performed genomic profiling of 425 cancer-relevant genes from tumor/plasma biopsies from a total of 17,442 Chinese lung cancer patients using next generation sequencing (NGS). Patients' clinical characteristics and treatment histories were retrospectively studied. A total of 1162 patients (6.66%; 1162/17,442) were identified as having kinase fusions, including 906 adenocarcinomas (ADCs) and 35 squamous cell carcinomas (SCCs). In ADC, 170 unique gene fusion pairs were observed, including rare kinase fusions, SLC12A2-ROS1, NCOA4-RET, and ANK3-RET. As for SCC, 15 unique gene fusions were identified, among which the most frequent were EML4-ALK and FGFR3-TACC3. Analyses of oncogenic mutations revealed a dual role for the gene fusions, CCDC6-RET and FGFR3-TACC3, in driving oncogenesis or serving as acquired resistance mechanisms to kinase inhibitors. In addition, our real-world evidence showed that patients with recurrent kinase fusions with low frequency (two occurrences) could benefit from treatment with kinase inhibitors' off-label use. Notably, patients with stage IV ADC who had novel RORB-ALK or AFF2-RET fusions, but no other known oncogenic driver mutations, demonstrated favorable clinical outcomes on tyrosine kinase inhibitors. Our data provide a comprehensive overview of the landscape of oncogenic kinase fusions in lung cancer, which assist in recognizing potentially druggable fusions that can be translated into therapeutic applications.
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http://dx.doi.org/10.1038/s41698-021-00221-zDOI Listing
September 2021

An Update on Targeted Treatment of IgA Nephropathy: An Autoimmune Perspective.

Authors:
Xin Huang Gaosi Xu

Front Pharmacol 2021 23;12:715253. Epub 2021 Aug 23.

Department of Nephrology, The Second Affiliated Hospital of Nanchang University, Nanchang, China.

Immunoglobulin (Ig) A nephropathy (IgAN) is the commonest form of primary glomerulonephritis worldwide and is, considered a significant cause of end-stage renal disease in young adults. The precise pathogenesis of IgAN is unclear. The clinical and pathological features vary significantly between individuals and races, which makes treating IgAN difficult. Currently, the therapeutic strategies in IgAN are still optimal blood pressure control and proteinuria remission to improve the renal function in most cases. Immunosuppressive drugs such as corticosteroids can be considered in patients with persistent proteinuria and a high risk of renal function decline; however, they include a high toxicity profile. Therefore, the safety and selectivity of medications are critical concerns in the treatment of IgAN. Various pharmacological therapeutic targets have emerged based on the evolving understanding of the autoimmune pathogenesis of IgAN, which involves the immune response, mucosal immunity, renal inflammation, complement activation, and autophagy; treatments based on these mechanisms have been explored in preclinical and clinical studies. This review summarizes the progress concerning targeted therapeutic strategies and the relevant autoimmune pathogenesis in IgAN.
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http://dx.doi.org/10.3389/fphar.2021.715253DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8419281PMC
August 2021

Monitoring water quality using proximal remote sensing technology.

Sci Total Environ 2021 Aug 21;803:149805. Epub 2021 Aug 21.

State Key Laboratory of Lake Science and Environment, Nanjing Institute of Geography and Limnology, Chinese Academy of Sciences, Nanjing 210008, China; University of Chinese Academy of Sciences, Beijing 100049, China.

Accurate, high spatial and temporal resolution water quality monitoring in inland waters is vital for environmental management. However, water quality monitoring in inland waters by satellite remote sensing remains challenging due to low signal-to-noise ratios (SNRs) and instrumental resolution limitations. We propose the concept of proximal remote sensing for monitoring water quality. The proximal hyperspectral imager, developed by Nanjing Institute of Geography and Limnology, Chinese Academy of Sciences (CAS) and Hikvision Digital Technology, Ltd., is a high spatial, temporal and spectral resolution (1 nm) sensor for continuous observation, allowing for effective and practical long-term monitoring of inland water quality. In this study, machine learning and empirical algorithms were developed and validated using in situ total nitrogen (TN), total phosphorus (TP), chemical oxygen demand (COD) concentrations and spectral reflectance from Lake Taihu (N = 171), the Liangxi River (N = 94) and the Fuchunjiang Reservoir (N = 109) covering different water quality. Our dataset includes a large range for three key water quality parameters of TN from 0.93 to 6.46 mg/L, TP from 0.04 to 0.62 mg/L, and COD from 1.32 to 15.41 mg/L. Overall, the back-propagation (BP) neural network model had an accuracy of over 80% for TN (R = 0.84, RMSE = 0.33 mg/L, and MRE = 11.4%) and over 90% for TP (R = 0.93, RMSE = 0.02 mg/L, and MRE = 12.4%) and COD (R = 0.91, RMSE = 0.66 mg/L, and MRE = 9.3%). Our results show that proximal remote sensing combined with machine learning algorithms has great potential for monitoring water quality in inland waters.
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http://dx.doi.org/10.1016/j.scitotenv.2021.149805DOI Listing
August 2021

PD-1 and TIGIT Are Highly Co-Expressed on CD8 T Cells in AML Patient Bone Marrow.

Front Oncol 2021 18;11:686156. Epub 2021 Aug 18.

The Clinical Medicine Postdoctoral Research Station, Department of Hematology, First Affiliated Hospital; Jinan University, Guangzhou, China.

Despite the great success of immune-checkpoint inhibitor (ICI) treatment for multiple cancers, evidence for the clinical use of ICIs in acute myeloid leukemia (AML) remains inadequate. Further exploration of the causes of immune evasion in the bone marrow (BM) environment, the primary leukemia site, and peripheral blood (PB) and understanding how T cells are affected by AML induction chemotherapy or the influence of age may help to select patients who may benefit from ICI treatment. In this study, we comprehensively compared the distribution of PD-1 and TIGIT, two of the most well-studied IC proteins, in PB and BM T cells from AML patients at the stages of initial diagnosis, complete remission (CR), and relapse-refractory (R/R) disease after chemotherapy. Our results show that PD-1 was generally expressed higher in PB and BM T cells from (DN) and R/R patients, while it was partially recovered in CR patients. The expression of TIGIT was increased in the BM of CD8 T cells from DN and R/R patients, but it did not recover with CR. In addition, according to age correlation analysis, we found that elderly AML patients possess an even higher percentage of PD-1 and TIGIT single-positive CD8 T cells in PB and BM, which indicate greater impairment of T cell function in elderly patients. In addition, we found that both DN and R/R patients accumulate a higher frequency of PD-1 and TIGIT CD8 T cells in BM than in corresponding PB, indicating that a more immunosuppressive microenvironment in leukemia BM may promote disease progression. Collectively, our study may help guide the combined use of anti-PD-1 and anti-TIGIT antibodies for treating elderly AML patients and pave the way for the exploration of strategies for reviving the immunosuppressive BM microenvironment to improve the survival of AML patients.
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http://dx.doi.org/10.3389/fonc.2021.686156DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8416522PMC
August 2021

A Review on Signal Processing Approaches to Reduce Calibration Time in EEG-Based Brain-Computer Interface.

Front Neurosci 2021 19;15:733546. Epub 2021 Aug 19.

Youth League Committee, Jiangxi University of Traditional Chinese Medicine, Nanchang, China.

In an electroencephalogram- (EEG-) based brain-computer interface (BCI), a subject can directly communicate with an electronic device using his EEG signals in a safe and convenient way. However, the sensitivity to noise/artifact and the non-stationarity of EEG signals result in high inter-subject/session variability. Therefore, each subject usually spends long and tedious calibration time in building a subject-specific classifier. To solve this problem, we review existing signal processing approaches, including transfer learning (TL), semi-supervised learning (SSL), and a combination of TL and SSL. Cross-subject TL can transfer amounts of labeled samples from different source subjects for the target subject. Moreover, Cross-session/task/device TL can reduce the calibration time of the subject for the target session, task, or device by importing the labeled samples from the source sessions, tasks, or devices. SSL simultaneously utilizes the labeled and unlabeled samples from the target subject. The combination of TL and SSL can take advantage of each other. For each kind of signal processing approaches, we introduce their concepts and representative methods. The experimental results show that TL, SSL, and their combination can obtain good classification performance by effectively utilizing the samples available. In the end, we draw a conclusion and point to research directions in the future.
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http://dx.doi.org/10.3389/fnins.2021.733546DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8417074PMC
August 2021

Mutational characteristics of bone metastasis of lung cancer.

Ann Palliat Med 2021 Aug;10(8):8818-8826

Department of Orthopedics, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China.

Background: Roughly 30-40% of lung cancer (LC) patients develop bone metastasis during the course of disease. The genetic differences between primary LC and matched bone metastasis are not yet fully understood.

Methods: A total of 40 LC patients with bone metastasis were collected and 450 targeted cancer-related genes were sequenced for genomic-alteration (GA) identification.

Results: Among the 40 LC patients, 33 had adenocarcinomas and 7 had squamous cell carcinomas. The metastatic sites of the 33 lung adenocarcinomas (LUADs) were the pelvis (6 patients), spine (16 patients), and limbs (11 patients). A total of 425 and 422 GAs were detected in the primary and metastatic lesions, respectively. The most common GAs were epidermal growth factor receptor (EGFR) mutations, which had mutation rates of 85.0% and 72.5% in the primary and metastatic lesions, respectively, and tumor protein 53 (TP53) mutations, which had mutation rates of 52.5% and 67.5% in the primary and metastatic lesions, respectively. Metastases to the pelvis and spine were most commonly accompanied by factor receptor substrate 2 (FRS2), cyclin-dependent kinase 4 (CDK4), and murine double minute 2 (MDM2) amplification, and cyclin-dependent kinase inhibitor 2A (CDKN2A) deletion. The concordance between primary lung squamous cell carcinoma (LUSC) and corresponding metastasis was significantly higher than that of primary LUAD and corresponding metastasis (P=0.033). Compared to limb and pelvis metastases, the shared mutation in spine metastasis was significantly lower (P=0.016 and P=0.023, respectively). In matched primary LUSCs and bone metastasis lesions, there was no significant difference in the distribution of the tumor mutational burden (TMB) (P=0.9). Conversely, a significant difference of the TMB distribution was detected in pairs of primary LUAD and corresponding bone metastasis lesions (P=0.021).

Conclusions: The consistency of mutation patterns between primary LC lesions and matched bone metastases may vary in terms of metastatic sites, but is very high in general. There was a significant difference in the TMB between primary LUAD and matched bone metastatic lesions. Our findings contribute to molecular understandings of primary LC and matched bone metastatic lesions.
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http://dx.doi.org/10.21037/apm-21-1595DOI Listing
August 2021

Mapping Regional Homogeneity and Functional Connectivity of the Visual Cortex in Resting-State fMRI.

J Vis Exp 2021 Aug 17(174). Epub 2021 Aug 17.

Eye Center, Renmin Hospital of Wuhan University;

A combined regional homogeneity (ReHo) and functional connectivity (FC) method, a type of noninvasive functional magnetic resonance imaging (fMRI) method, has been used to evaluate synchronous neuronal activity changes in retinitis pigmentosa (RP). The purpose of this study is to describe our method for analysis of intra- and interregional synchronizations of changes in neuronal activity in RP patients. The advantages of the combined ReHo and FC method are that it is both noninvasive and sufficiently sensitive to investigate changes in cerebral synchronous neuronal activity changes in vivo. Here, 16 RP patients and 14 healthy controls closely matched in age, sex, and education underwent resting-state fMRI scans. Two sample t-tests were conducted to compare ReHo and FC across groups. Our results showed that visual network disconnection and reorganization of the retino-thalamocortical pathway and dorsal visual stream occurred in the RP patients. Here, we describe the details of this method, its use, and the impact of its key parameters in a step-by-step manner.
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http://dx.doi.org/10.3791/60305DOI Listing
August 2021

Effects of steam-flaked grains on foals' growth and faecal microbiota.

BMC Vet Res 2021 Sep 4;17(1):293. Epub 2021 Sep 4.

College of Animal Science, Xinjiang Key Laboratory of Herbivore Nutrition for Meat & Milk Production, Xinjiang Agricultural University, Xinjiang, 830052, Urumqi, China.

Background: There is little objective information concerning the effect of steam-flaked grains on foal's growth performance and faecal microbiota. To determine the effects of steam-flaked grains on foal's growth performance and faecal microbiota, faecal samples were collection from 18 foals which had been fed either corn, oat or barley diets over the 60 days of the experiment. Body weight and conformation measurements were collected. Next-generation sequencing of the V3 + V4 region of the 16 S rRNA gene was used to assess the microbial composition of faeces. Alpha diversity, Venn graph, Relative abundance and beta diversity are presented.

Results: There was a significantly higher larger increase in the body weight of those foals fed barley compared to either corn or oats. There were also significant changes in the Alpha diversity of the gut microbiota. The Shannon and Simpson indices were significantly higher in the barley fed group than those fed corn or oats. The Chao1 index was significantly higher in the oat fed group than the corn or barley fed groups. There were significant changes in the relative abundance of bacteria in the microbiota in terms of phylum, family and genus. The histogram of LDA value distribution showed that the 12 statistically different biomarkers of the bacteria were present. Tax4Fun function annotation clustering heat map showed that functional information was detected from 26 species of bacteria in faecal samples from the foals.

Conclusions: Differences by starch sources were found in overall growth of the foals and in the faecal microbiota if either supplementary corn, oat or barley was fed. Further studies are required to determine the potential impact of the changes in the microbiota on the health and development of foals fed cereal starch of different sources.
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http://dx.doi.org/10.1186/s12917-021-02994-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8418754PMC
September 2021

Inherently nitric oxide containing polymersomes remotely regulated by NIR for improving multi-modal therapy on drug resistant cancer.

Biomaterials 2021 Sep 1;277:121118. Epub 2021 Sep 1.

Department of Pharmaceutical Engineering, School of Engineering, China Pharmaceutical University, Nanjing, 210009, China; Engineering Research Center for Smart Pharmaceutical Manufacturing Technologies, Ministry of Education, School of Engineering, China Pharmaceutical University, Nanjing, 210009, China. Electronic address:

The therapeutic potential of nitric oxide (NO) has been highly attractive to tumor treatment, especially for surmounting the multidrug resistance (MDR) of cancer. However, the NO-involved therapy remains extremely challenging because of the difficulty to simultaneously control the NO release rate and real-time concentration. Herein, we construct NO-containing polymersomes with high amount of NO donors inherently grown on the polymer chains to keep the stability. These polymersomes can be simultaneously loaded with photosensitizer of IR780 iodide on the membrane layer and chemotherapeutic of DOX·HCl in the lumen. NO release can be triggered by the reduction conditions, and further accelerated by remote NIR irradiation due to the increased local temperature. The instantaneous NO release with high concentration significantly inhibits the P-gp expression and sensitize the chemotherapy, thus overcoming the tumor MDR and improving the anti-tumor activity. Meanwhile, DOX·HCl release is highly promoted at the intracellular conditions because of the cleavage of acid-labile cis-aconitic amide at endo/lysosomal pH, and the improved hydrophilicity of the membrane layer after NO release. The in vivo results show that the single intravenous injection of polymersome formulation companying with NIR irradiation exerts multi-modal therapies of chemotherapy, PTT/PDT, and NO-therapy on the MCF-7/R tumor models, showing superior and combinational treatment efficacy with the complete eradication of tumors and few side effects.
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http://dx.doi.org/10.1016/j.biomaterials.2021.121118DOI Listing
September 2021

Activity-based photoacoustic probe for biopsy-free assessment of copper in murine models of Wilson's disease and liver metastasis.

Proc Natl Acad Sci U S A 2021 Sep;118(36)

Department of Chemistry, The Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, Urbana, IL 61801

The development of high-performance photoacoustic (PA) probes that can monitor disease biomarkers in deep tissue has the potential to replace invasive medical procedures such as a biopsy. However, such probes must be optimized for in vivo performance and exhibit an exceptional safety profile. In this study, we have developed PACu-1, a PA probe designed for biopsy-free assessment (BFA) of hepatic Cu via photoacoustic imaging. PACu-1 features a Cu(I)-responsive trigger appended to an aza-BODIPY dye platform that has been optimized for ratiometric sensing. Owing to its excellent performance, we were able to detect basal levels of Cu in healthy wild-type mice as well as elevated Cu in a Wilson's disease model and in a liver metastasis model. To showcase the potential impact of PACu-1 for BFA, we conducted two blind studies in which we were able to successfully identify Wilson's disease animals from healthy control mice in each instance.
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http://dx.doi.org/10.1073/pnas.2106943118DOI Listing
September 2021

Identification of four Spätzle genes (MnSpz1, MnSpz2, MnSpz2-isoform, and MnSpz3) and their roles in the innate immunity of Macrobrachium nipponense.

Dev Comp Immunol 2021 Sep 1;126:104254. Epub 2021 Sep 1.

Jiangsu Province Engineering Research Center for Aquatic Animals Breeding and Green Efficient Aquacultural Technology, College of Marine Science and Engineering, Nanjing Normal University, Nanjing, Jiangsu Province, 210023, China. Electronic address:

Spätzle, an extracellular ligand of the Toll receptor, is involved in the innate immunity of crustaceans. In this study, four Spätzle genes were cloned from Macrobrachium nipponense and designed as MnSpz1, MnSpz2, MnSpz2-isoform, and MnSpz3. The coding region of the four Spätzle genes all contained one intron and two exons, and they were predicted to be produced by gene duplication based on sequence similarities and phylogenetic tree. The predicted MnSpz1, MnSpz2, and MnSpz3 proteins all contained a signal peptide and a Spätzle domain. No signal peptide but a Spätzle domain existed in MnSpz2-isoform because of frameshift mutation caused by 50 bp nucleotide deletion compared with MnSpz2. Quantitative real-time polymerase chain reaction (RT-qPCR) analysis showed that MnSpz1, MnSpz2, and MnSpz3 were expressed in all the detected tissues of M. nipponense, and MnSpz2 was found to be the major isoform in the heart, gills, stomach, and intestine. After stimulation by Vibrio parahaemolyticus, Staphylococcus aureus, or White spot syndrome virus (WSSV), the expression levels of MnSpz1, MnSpz2, and MnSpz3 changed. Given the high similarities among MnSpz1-3, RNA interference (RNAi) using dsRNA of MnSpz1 inhibited the expression of the three Spätzle genes (MnSpz1, MnSpz2 and MnSpz3). Silencing of MnSpz1-3 down-regulated the expression levels of nine antimicrobial peptide (AMP) genes in M. nipponense. After Knockdown of MnSpzs, the number of V. parahaemolyticus, S. aureus and WSSV copies in M. nipponense increased significantly in vivo. Our results suggest that Spätzles are involved in the innate immunity of M. nipponense. The expansion of MnSpz genes through gene duplication is beneficial to enhance the innate immune defense ability of M. nipponense.
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http://dx.doi.org/10.1016/j.dci.2021.104254DOI Listing
September 2021

ZIF-8 engineered bismuth nanosheet arrays for boosted electrochemical reduction of nitrate.

Nanoscale 2021 Aug 4;13(32):13786-13794. Epub 2021 Aug 4.

National Engineering Research Center for Industry Crystallization Technology, School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, China.

Removal of nitrate in wastewater is of great importance to environmental protection and humanity. However, the competitive reaction of hydrogen evolution (HER), which could occupy most active sites of the electrocatalyst, is one of the big challenges for nitrate removal. In this study, a novel zeolitic imidazolate framework-8 film engineered bismuth nanosheet electrocatalyst (ZIF-8/Bi-CC) was designed and synthesized for the electrochemical reduction of nitrate. The water contact angle and electrochemical tests demonstrated that the construction of the hydrophobic ZIF-8 film effectively weakened the competition of HER. And the nitrate removal efficiency and ammonium selectivity increased by 25.9% and 34.2% respectively after bismuth nanosheets were embedded into the ZIF-8 film. Besides, the bismuth concentration detection results indicated that the ZIF-8 film as the protective shell could effectively prevent the leaching of bismuth into the solution. More importantly, the final nitrate removal rate of ZIF-8/Bi-CC was close to 90% after 5 h when treating actual garbage fly ash wastewater, the NITRR efficiency stability and the obtained product were confirmed by five electrochemical cycles. The metal-organic framework film engineered electrocatalyst is a promising strategy for designing a new catalyst for the removal of nitrate in industrial wastewater.
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http://dx.doi.org/10.1039/d1nr02339jDOI Listing
August 2021

Particular pollutants, physical properties, and environmental performance of porous ceramsite materials containing oil-based drilling cuttings residues.

Environ Sci Pollut Res Int 2021 Sep 1. Epub 2021 Sep 1.

Engineering Technology Research Institute of Petrochina Southwest Oil and Gas Field Company, Chengdu, 610017, Sichuan Province, China.

The mineral compositions of oil-based drilling cutting residues (ODCRs) were similar to that of clay, which could be used as raw materials for ceramsite. In this study, the maximum addition of ODCRs and the optimum calcination conditions were studied by single factor experiment. The microstructure, phase composition, and element distribution of ceramsite were studied by means of SEM, XRD and EDS. The ceramsite, with a 40% ODCRs content, was calcined at 1000 °C for 2 h. After cooling down, the ceramsite had good physical properties, including low density, low water absorption, and high compressive strength. The bulk density was 850-970 kg/m, the water absorption was 2.1-10%, and the cylinder compressive strength was 6-11.8 MPa. And most of the heavy metals in ODCRs were effectively solidified. The organic toxic substances were completely burned. The leaching amount of harmful elements met the requirements of Chinese standards. The ceramsite would avoid secondary pollution to the environment. So the ceramsite made from ODCRs can not only improve the processing speed of ODCRs, but also be used as building materials, greening materials, industrial filter materials, etc., and increase its environmental and social benefits.
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http://dx.doi.org/10.1007/s11356-021-16120-6DOI Listing
September 2021

Immunoadsorption with staphylococcal protein A column in autoimmune encephalitis.

Transfusion 2021 Sep 1. Epub 2021 Sep 1.

Department of Neurological Intensive Care Unit, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.

Background: Early treatment has a positive effect on autoimmune encephalitis. However, different treatments have individual differences and corresponding contraindications in the clinical. Few reports have described the application of immunoadsorption with Staphylococcal Protein A Column (SPA-IA) in neuroimmune diseases. We aimed to observe the safety and efficiency of SPA-IA in autoimmune encephalitis.

Patients And Methods: We retrospectively analyzed three cases of autoimmune encephalitis wherein the first-line treatment was ineffective or contraindicated. The clinical features and prognosis during and after SPA-IA are described in detail.

Results: All patients were definitely diagnosed with autoimmune encephalitis. After treated with SPA-IA, all antibody titers, except for the serum antibody titer in Patient 2, were markedly decreased in both the cerebral spinal fluid and serum. The mean fibrinogen levels before and after SPA-IA were stable, and there were no clinical bleeding events. The modified Rankin Scale scores and their symptoms improved significantly after the last SPA-IA session or 3 months later.

Conclusions: SPA-IA may be a viable, efficacious, and safe treatment alternative for autoimmune encephalitis with contraindications to traditional treatment or poor response.
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http://dx.doi.org/10.1111/trf.16644DOI Listing
September 2021

Combining protein and RNA quantification to evaluate promoter activity by using dual-color fluorescent reporting systems.

Biosci Rep 2021 Sep;41(9)

Natural Products Research Center, Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu, Sichuan 610041, P.R. China.

Herein, Broccoli/mCherry and an EGFP/mCherry dual-color fluorescent reporting systems have been established to quantify the promoter activity at transcription and translation levels in eukaryotic cells. Based on those systems, four commonly used promoters (CMV and SV40 of Pol II and U6, H1 of Pol III) were accurately evaluated at both the transcriptional and translational levels by combining accurate protein and RNA quantification. Furthermore, we verified that Pol III promoters can induce proteins expression, and Pol II promoter can be applied to express RNA molecules with defined length by combining a self-cleaving ribozyme and an artificial poly(A) tail. The dual-color fluorescence reporting systems described here could play a significant role in evaluating other gene expression regulators for gene therapy.
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http://dx.doi.org/10.1042/BSR20211525DOI Listing
September 2021

Puerarin Alleviates UUO-Induced Inflammation and Fibrosis by Regulating the NF-κB P65/STAT3 and TGFβ1/Smads Signaling Pathways.

Drug Des Devel Ther 2021 24;15:3697-3708. Epub 2021 Aug 24.

Department of Nephrology, The First Affiliated Hospital of China Medical University, Shenyang, 110000, Liaoning Province, People's Republic of China.

Purpose: Puerarin (PR), a Chinese medicine rich in natural components, has been reported to display anti-fibrotic, antioxidant, anti-inflammatory and immunomodulatory properties. However, the protective mechanism of PR against unilateral ureteral obstruction (UUO)-mediated renal injury is not fully clarified. Therefore, the aim of this study was to investigate the effects of PR on UUO mice and its possible mechanisms.

Methods: A total of 32 C57BL/6 mice were divided randomly into four groups (n=8): i) sham-operated group (Sham); ii) UUO group (UUO); iii) UUO + PR 50 mg/kg/day (UUO + PRL); and iv) UUO + PR 100 mg/kg/day (UUO + PRH). Continuous gavage administration for 14 days starting one week postoperatively, while the mice in Sham and UUO groups were given equal amounts of vehicle by the same means. All mice were then sacrificed and serum, 24-hour urine and tissue specimens were collected for renal function, histopathology, Western blot, immunohistochemistry.

Results: Renal function and histopathology revealed that PR improved UUO-mediated renal dysfunction and partially reversed tubular injury and tubulointerstitial fibrosis. Additionally, according to the results of Western blot and immunohistochemistry, PR inhibited the expression of inflammatory factors including IL-1β, IL-6, MCP-1 and ECM-related proteins including α-SMA, COL I and VIM. More importantly, the expression of fibrotic pathways TGF-β1, Smad3, p-Smad3 and inflammatory pathways NF-κB p65, NF-κB p-p65, STAT3, p-STAT3 were inhibited to various extents under the PR treatment, while Smad7 was upregulated.

Conclusion: These findings indicate that PR may inhibit the recruitment of inflammatory factors and extracellular matrix (ECM) deposition through the regulation of the NF-κB p65/STAT3 and TGFβ1/Smads pathways, which alleviates the UUO-induced inflammatory and fibrotic response, thereby reversing renal injury.
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http://dx.doi.org/10.2147/DDDT.S321879DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8402986PMC
August 2021

Clinical utiliy of a model-based piperacillin dose in neonates with early-onset sepsis.

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

Department of Clinical Pharmacy, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, China.

Aims: Early-onset sepsis (EOS) is a common disease in neonates with a high morbidity and mortality rate. Piperacillin/tazobactam has been used extensively and empirically for EOS treatment without clinically validated dosing regimens, although the population pharmacokinetics (PPK) of piperacillin in neonates has been reported. Therefore, we wanted to study the effectiveness and tolerance of a PPK model-based dosing regimen of piperacillin/tazobactam in EOS patients.

Methods: A prospective, single-center, phase II clinical study of piperacillin/tazobactam in neonates with EOS was conducted. The dosing regimen (90 mg·kg , q8h) was determined based on a previous piperacillin PPK model in young infants (Cohen-Wolkowiez et al., 2014) using NONMEM v7.4. The pharmacodynamics (PD) target (70%fT>MIC, free drug concentration above MIC during 70% of the dosing interval) attainment was calculated using NONMEM combined with an opportunistic sampling design. The clinical treatment data were collected.

Results: A total of 52 neonates were screened and 49 neonates completed their piperacillin/tazobactam treatment course and were included in this analysis. The median (range) values of postmenstrual age were 33.57 (range 26.14-41.29) weeks. Forty-seven (96%) neonates reached their PD target. Eight (16%) neonates experienced treatment failure clinically. The mean (SD, range) duration of treatment and length of hospitalization were 100.1 (62.2, 36.2-305.8) hours and 31 (30, 5-123) days. There were no obvious adverse events and no infection-related deaths occurred in the first month of life.

Conclusions: A model-based dosing regimen of piperacillin/tazobactam optimized was evaluated clinically and was tolerated well and effective for EOS treatment.
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http://dx.doi.org/10.1111/bcp.15058DOI Listing
August 2021

Characterization and functional analysis of a clip domain serine protease (MncSP) and its alternative transcript (MncSP-isoform) from Macrobrachium nipponense.

Dev Comp Immunol 2021 Aug 25;126:104237. Epub 2021 Aug 25.

Jiangsu Province Engineering Research Center for Aquatic Animals Breeding and Green Efficient Aquacultural Technology, College of Marine Science and Engineering, Nanjing Normal University, Nanjing, Jiangsu Province, 210023,China. Electronic address:

Clip domain serine protease (cSPs) play an important role in the innate immune defense of crustaceans. In this study, a clip domain serine protease (MncSP) and its alternative transcript (MncSP-isoform) were identified from Macrobrachium nipponense. The full-length cDNA sequences of MncSP and MncSP-isoform were 2447 and 2351 bp with open reading frames comprising 1497 and 1401 bp nucleotides and encoding 498 and 466 amino acids, respectively. The genome of MncSP had 10 exons and 9 introns. MncSP contained all 10 exons, whereas MncSP-isoform lacked the second exon. MncSP and MncSP-isoform contained a signal peptide, a clip domain, and a Tryp_SPc domain. Phylogenetic tree analysis showed that MncSP and MncSP-isoform clustered with cSPs from Palaemonidae. MncSP and MncSP-isoform were widely distributed in hemocytes, heart, hepatopancreas, gills, stomach, and intestine. The expression profiles of MncSP and MncSP-isoform in the hemocytes of M. nipponense changed after simulation by Vibrio parahaemolyticus or Staphylococcus aureus. The RNAi of MncSP could inhibit the expression of antimicrobial peptides (AMPs), including crustins and anti-lipopolysaccharide factors. Phenoloxidase activity was also down-regulated in MncSP-silenced prawns. This study indicated that MncSP participated in the synthesis of AMPs and the activation of prophenoloxidase.
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http://dx.doi.org/10.1016/j.dci.2021.104237DOI Listing
August 2021

Perceptual learning as a result of concerted changes in prefrontal and visual cortex.

Curr Biol 2021 Aug 20. Epub 2021 Aug 20.

State Key Laboratory of Cognitive Neuroscience and Learning & IDG/McGovern Institute for Brain Research, Beijing Normal University, Beijing 100875, China; College of Life Sciences, Beijing Normal University, Beijing 100875, China. Electronic address:

Our perceptual ability remarkably improves with training. Some studies on visual perceptual learning have shown refined neural representation of the trained stimulus in the visual cortex, whereas others have exclusively argued for improved readout and decision-making processes in the frontoparietal cortex. The mixed results have rendered the underlying neural mechanisms puzzling and hotly debated. By simultaneously recording from monkey visual area V4 and ventrolateral prefrontal cortex (PFC) implanted with microelectrode arrays, we dissected learning-induced cortical changes over the course of training the monkeys in a global form detection task. Decoding analysis dissociated two distinct components of neuronal population codes that were progressively and markedly enhanced in both V4 and PFC. One component was closely related to the target stimulus feature and was subject to task-dependent top-down modulation; it emerged earlier in V4 than PFC and its enhancement was specific to the trained configuration of the target stimulus. The other component of the neural code was entirely related to the animal's behavioral choice; it emerged earlier in PFC than V4 and its enhancement completely generalized to an untrained stimulus configuration. These results implicate two concurrent and synergistic learning processes: a perceptual process that is specific to the details of the trained stimulus feature and a cognitive process that is dependent on the total amount of learning experience in the trained task. When combined, these two learning processes were well predictive of the animal's learning behavior.
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http://dx.doi.org/10.1016/j.cub.2021.08.007DOI Listing
August 2021

OCT4 cooperates with distinct ATP-dependent chromatin remodelers in naïve and primed pluripotent states in human.

Nat Commun 2021 08 26;12(1):5123. Epub 2021 Aug 26.

Department of Developmental Biology, Washington University School of Medicine, St. Louis, MO, USA.

Understanding the molecular underpinnings of pluripotency is a prerequisite for optimal maintenance and application of embryonic stem cells (ESCs). While the protein-protein interactions of core pluripotency factors have been identified in mouse ESCs, their interactome in human ESCs (hESCs) has not to date been explored. Here we mapped the OCT4 interactomes in naïve and primed hESCs, revealing extensive connections to mammalian ATP-dependent nucleosome remodeling complexes. In naïve hESCs, OCT4 is associated with both BRG1 and BRM, the two paralog ATPases of the BAF complex. Genome-wide location analyses and genetic studies reveal that these two enzymes cooperate in a functionally redundant manner in the transcriptional regulation of blastocyst-specific genes. In contrast, in primed hESCs, OCT4 cooperates with BRG1 and SOX2 to promote chromatin accessibility at ectodermal genes. This work reveals how a common transcription factor utilizes differential BAF complexes to control distinct transcriptional programs in naïve and primed hESCs.
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http://dx.doi.org/10.1038/s41467-021-25107-3DOI Listing
August 2021

Identification and Antioxidant Abilities of Enzymatic-Transesterification (-)-Epigallocatechin-3--gallate Stearyl Derivatives in Non-Aqueous Systems.

Antioxidants (Basel) 2021 Aug 13;10(8). Epub 2021 Aug 13.

State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, China.

Vinyl stearate was added to enzymatic transesterification of (-)-Epigallocatechin-3--gallate (EGCG) to enhance its lipophilicity and antioxidant ability in a non-aqueous system. The lipase DF "Amano" 15 was used as the catalyst. The optimal reaction conditions were: acetonitrile as the solvent, the molar ratio of vinyl stearate: EGCG as 3:1, an enzyme amount of 4.0% (ratio of substrate mass), and a reaction temperature and time of 50 °C and 96 h, respectively, achieving 65.2% EGCG conversion. HPLC-MS and NMR were used to determine the structure of EGCG stearyl derivative (3″,5″-2-O-stearyl-EGCG). The lipophilicity of EGCG stearyl derivatives (3.49 ± 0.34) was higher (5.06 times) than that of the parent EGCG (0.69 ± 0.08). Furthermore, EGCG stearyl derivatives had excellent lipid oxidation compared with BHT, BHA, and parent EGCG. The POVs of soybean oil with EGCG stearyl derivatives (18.17 ± 0.92 mEq/kg) were significantly reduced (by 62.5%) at 21 d compared with those of EGCG (48.50 ± 1.23 mEq/kg). These results indicate that EGCG derivatives have broad antioxidant application prospects in lipophilic environments/high-fat food.
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http://dx.doi.org/10.3390/antiox10081282DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8389292PMC
August 2021

Veliparib in Combination With Platinum-Based Chemotherapy for First-Line Treatment of Advanced Squamous Cell Lung Cancer: A Randomized, Multicenter Phase III Study.

J Clin Oncol 2021 Aug 26:JCO2003318. Epub 2021 Aug 26.

Toulouse University Hospital, Institut Universitaire du Cancer, Université Paul Sabatier, Toulouse, France.

Purpose: Squamous non-small-cell lung cancer (sqNSCLC) is genetically complex with evidence of DNA damage. This phase III study investigated the efficacy and safety of poly (ADP-ribose) polymerase inhibitor veliparib in combination with conventional chemotherapy for advanced sqNSCLC (NCT02106546).

Patients And Methods: Patients age ≥ 18 years with untreated, advanced sqNSCLC were randomly assigned 1:1 to carboplatin and paclitaxel with veliparib 120 mg twice daily (twice a day) or placebo twice a day for up to six cycles. The primary end point was overall survival (OS) in the veliparib arm versus the control arm in current smokers, based on phase II findings. Archival tumor samples were provided for biomarker analysis using a 52-gene expression histology classifier (LP52).

Results: Overall, 970 patients were randomly assigned to carboplatin and paclitaxel plus either veliparib (n = 486) or placebo (n = 484); 57% were current smokers. There was no significant OS benefit with veliparib in current smokers, with median OS 11.9 versus 11.1 months (hazard ratio [HR], 0.905; 95% CI, 0.744 to 1.101; = .266). In the overall population, OS favored veliparib; median OS was 12.2 versus 11.2 months (HR, 0.853; 95% CI, 0.747 to 0.974), with no difference in progression-free survival (median 5.6 months per arm). In patients with biomarker-evaluable tumor samples (n = 360), OS favored veliparib in the LP52-positive population (median 14.0 9.6 months; HR, 0.66; 95% CI, 0.49 to 0.89), but favored placebo in the LP52-negative population (median 11.0 14.4 months; HR, 1.33; 95% CI, 0.95 to 1.86). No new safety signals were observed in the experimental arm.

Conclusion: In current smokers with advanced sqNSCLC, there was no therapeutic benefit of adding veliparib to first-line chemotherapy. The LP52 signature may identify a subgroup of patients likely to derive benefit from veliparib with chemotherapy.
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http://dx.doi.org/10.1200/JCO.20.03318DOI Listing
August 2021
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