Publications by authors named "Tingting Huang"

228 Publications

Shengxuening Extracted from Silkworm Excrement Mitigates Myelosuppression via SCF-Mediated JAK2/STAT3 Signaling.

Chem Biodivers 2021 May 11. Epub 2021 May 11.

Department of Hematology, Zhongnan Hospital of Wuhan University, No. 169 Donghu Road, Wuhang District, Wuhan, 430071, P. R. China.

Shengxuening (SXN) is a Chinese patent medicine with main ingredients (including chlorophyll derivatives and sodium iron chlorophyllin) extracted from silkworm excrement. SXN exhibited efficacy in clinical trials of renal anemia and iron deficiency anemia; however, the specific mechanisms remain unclear. This study found that SXN increased the number of peripheral blood cells and improved the bone marrow morphology in myelosuppressed mouse model, reversed the reduction in body weight and spleen indices, and increased the serum levels of erythropoietin and granulocyte-macrophage colony-stimulating factor. Quantitative real-time PCR array and Western blot analysis showed the enhanced expression of stem cell factor (SCF), JAK2, and STAT3 in the liver. These results suggested that SXN promoted the recovery of hemopoietic function in myelosuppressed models by increasing the secretion of hematopoietic factors and activating the JAK2/STAT3 pathway. Therefore, this medicine may be applied as therapeutic pharmaceutical drug to mitigate myelosuppression.
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http://dx.doi.org/10.1002/cbdv.202100139DOI Listing
May 2021

Dietary patterns and risk of nasopharyngeal carcinoma: a population-based case-control study in southern China.

Am J Clin Nutr 2021 May 8. Epub 2021 May 8.

Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden.

Background: Dietary factors, such as consumption of preserved foods, fresh vegetables, and fruits, have been linked to the risk of nasopharyngeal carcinoma (NPC). However, little is known about associations between dietary patterns and the risk of NPC in NPC-endemic areas.

Objectives: We aimed to evaluate whether dietary patterns are associated with NPC risk.

Methods: We studied 2554 newly diagnosed NPC patients aged 20-74 y living in 3 endemic regions of southern China, and 2648 population-based controls frequency-matched to case patients by age, sex, and region, between 2010 and 2014. Dietary components were derived from food frequency data in adulthood and adolescence using principal component analysis. Four dietary components were identified and highly similar in adulthood and adolescence. We used multivariable unconditional logistic regression to calculate ORs with 95% CIs for the association between dietary patterns and NPC risk.

Results: Compared with the lowest quartile, individuals in the highest quartile of the "plant-based factor" in adulthood had a 52% (OR: 0.48; 95% CI: 0.38, 0.59) decreased risk of NPC, and those in the highest quartile of the "animal-based factor" had a >2-fold (OR: 2.26; 95% CI: 1.85, 2.77) increased risk, with a monotonic dose-response trend (P-trend < 0.0001). Similar but weaker associations were found in adolescence. High intakes of the "preserved-food factor" were associated with increased NPC risk in both periods, although stronger associations were found in adolescence. Results from joint analysis and sensitivity analyses indicated that dietary factors in adulthood might be more stable and robust predictors of NPC risk than those in adolescence.

Conclusions: Our results deliver compelling evidence that plant- and animal-based dietary factors are associated with NPC risk, and provide more insights on the associations of diets and cancer risk that may assist healthy diet recommendations.
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http://dx.doi.org/10.1093/ajcn/nqab114DOI Listing
May 2021

Clinical and genetic analysis of a case with centronuclear myopathy caused by SPEG gene mutation: a case report and literature review.

BMC Pediatr 2021 Apr 29;21(1):209. Epub 2021 Apr 29.

Department of Pediatrics, Peking University First Hospital, No.1 Xi'an Men Street, West District, Beijing, 100034, China.

Background: Centronuclear myopathy (CNM), a subtype of congenital myopathy (CM), is a group of clinical and genetically heterogeneous muscle disorders. Since the discovery of the SPEG gene and disease-causing variants, only a few additional patients have been reported.

Case Presentation: The child, a 13-year-old female, had delayed motor development since childhood, weakness of both lower extremities for 10 years, gait swinging, and a positive Gower sign. Her distal muscle strength of both lower extremities was grade IV. The electromyography showed myogenic damage and electromyographic changes. Her 11-year-old sister had a similar muscle weakness phenotype. Gene sequencing revealed that both sisters had SPEG compound heterozygous mutations, and the mutation sites were c.3715 + 4C > T and c.3588delC, which were derived from their parents. These variant sites have not been reported before. The muscle biopsy showed the nucleic (> 20% of fibers) were located in the center of the cell, the average diameter of type I myofibers was slightly smaller than that of type II myofibers, and the pathology of type I myofibers was dominant, which agreed with the pathological changes of centronuclear myopathy.

Conclusions: The clinical phenotypes of CNM patients caused by mutations at different sites of the SPEG gene are also different. In this case, there was no cardiomyopathy. This study expanded the number of CNM cases and the mutation spectrum of the SPEG gene to provide references for prenatal diagnosis and genetic counseling.
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http://dx.doi.org/10.1186/s12887-021-02656-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8082920PMC
April 2021

Connectome-based prediction of brain age in Rolandic epilepsy: a protocol for a multicenter cross-sectional study.

Ann Transl Med 2021 Mar;9(6):511

Department of Radiology, the Affiliated Hospital of Zunyi Medical University, Medical Imaging Center of Guizhou Province, Zunyi, China.

Background: Rolandic epilepsy (RE) is a common pediatric idiopathic partial epilepsy syndrome. Children with RE display varying degrees of cognitive impairment. In epilepsy, age-related neuroanatomic and cognitive changes differ greatly from those observed in the healthy brain, and may be defined as accelerated brain aging. Connectome-based predictive modeling (CPM) is a recently developed machine learning approach that uses whole-brain connectivity measured with neuroimaging data ("neural fingerprints") to predict brain-behavior relationships. The aim of the study will be to develop and validate a CPM for predicting brain age in patients with RE.

Methods: A multicenter, cross-sectional study will be conducted in 5 Chinese hospitals. A total of 100 RE patients (including 50 patients receiving anti-epileptic drugs and 50 drug-naïve patients) and 100 healthy children will be recruited to undergo a neuropsychological test using the Wechsler Intelligence Scale. Magnetic resonance images will also be collected. CPM will be applied to predict the brain age of children with RE based on brain functional connectivity.

Discussion: The findings of the study will facilitate our understanding of developmental changes in the brain in children with RE and could also be an important milestone in the journey toward developing effective early interventions for this disorder.

Trial Registration: The study has been registered with Chinese Clinical Trial Registry (ChiCTR2000032984).
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http://dx.doi.org/10.21037/atm-21-574DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8039653PMC
March 2021

Vitamin K2 protects against Aβ42-induced neurotoxicity by activating autophagy and improving mitochondrial function in Drosophila.

Neuroreport 2021 Apr;32(6):431-437

Department of Neurology, The First Affiliated Hospital of Guangxi Medical University, Nanning.

Objective: Alzheimer disease is characterized by progressive decline in cognitive function due to neurodegeneration induced by accumulation of Aβ and hyperphosphorylated tau protein. This study was conducted to explore the protective effect of vitamin K2 against Aβ42-induced neurotoxicity.

Methods: Alzheimer disease transgenic Drosophila model used in this study was amyloid beta with the arctic mutation expressed in neurons. Alzheimer disease flies were treated with vitamin K2 for 28 days after eclosion. Aβ42 level in brain was detected by ELISA. Autophagy-related genes and NDUFS3, the core subunit of mitochondrial complex I, were examined using real-Time PCR (RT-PCR) and western blot analysis.

Results: Vitamin K2 improved climbing ability (P = 0.0105), prolonged lifespan (P < 0.0001) and decreased Aβ42 levels (P = 0.0267), upregulated the expression of LC3 and Beclin1(P = 0.0012 and P = 0.0175, respectively), increased the conversion of LC3I to LC3II (P = 0.0206) and decreased p62 level (P =0.0115) in Alzheimer disease flies. In addition, vitamin K2 upregulated the expression of NDUFS3 (P = 0.001) and increased ATP production (P = 0.0033) in Alzheimer disease flies.

Conclusion: It seems that vitamin K2 protect against Aβ42-induced neurotoxicity by activation of autophagy and rescue mitochondrial dysfunction, which suggests that it may be a potential valuable therapeutic approach for Alzheimer disease.
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http://dx.doi.org/10.1097/WNR.0000000000001599DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8016515PMC
April 2021

The gut microbiome in subclinical atherosclerosis: a population-based multi-phenotype analysis.

Rheumatology (Oxford) 2021 Mar 26. Epub 2021 Mar 26.

State Key Laboratory of Genetic Engineering and Human Phenome Institute, and School of Life Sciences, Fudan University, Shanghai, China.

Background: The altered microbiota, considered as quantitative traits, has also been identified to play pivotal roles in the host vascular physiology and might contribute to diseases. To understand the role of gut microbiota on vascular physiology in the sub-clinical elderly population and how lifestyles affect the composition of host gut microbiota to further impact the pathogenesis of vascular diseases.

Methods: Performed a population-based fecal metagenomic study over 569 elderly asymptomatic sub-clinical individuals in rural China. An association network was built based on clinical measurements and detailed epidemiologic questionnaires, including blood chemistry, arterial stiffness, carotid ultrasonography, and metagenomic datasets.

Results: Carotid arterial atherosclerosis indices, including intima-media thickness (IMT), were shown essentially in the network, and were significantly associated with living habits, socio-economic status, and diet. Using mediation analysis, we found that higher frequency of taking fresh fruits, fresh vegetables, and more exercise significantly reduces carotid arteries atherosclerosis in terms of IMT, PSV and EDV values the through the mediation of Alistepes, Oligella, and Prevotella. The gut microbes explained 16.5% of the mediation effect of lifestyles on the pathogenesis of carotid atherosclerosis. After adjusted, Faecalicatena (OR = 0.20∼0.30) was shown protective in the formation of carotid athersclerosis independently, while Libanicoccus (OR = 2.39∼2.43) were hazardous to carotid arterial IMTs. KEGG/KO analyses revealed a loss of anti-inflammation function in IMT subjects.

Conclusions: Our study provided a Chinese population-wide phenotype-metagenomic network, revealing association and mediation effect of gut microbiota on carotid artery atherosclerosis, hinting at a therapeutic and preventive potential of microbiota in vascular diseases.
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http://dx.doi.org/10.1093/rheumatology/keab309DOI Listing
March 2021

Submerged fermentation of Streptomyces uncialis providing a biotechnology platform for uncialamycin biosynthesis, engineering, and production.

J Ind Microbiol Biotechnol 2021 Mar 19. Epub 2021 Mar 19.

Department of Chemistry, The Scripps Research Institute, Jupiter, Florida 33458, USA.

Uncialamycin (UCM) belongs to the anthraquinone-fused subfamily of 10-membered enediyne natural products that exhibits an extraordinary cytotoxicity against a wide spectrum of human cancer cell lines. Antibody-drug conjugates (ADCs), utilizing synthetic analogues of UCM as payloads, are in preclinical development. UCM is exclusively produced by Streptomyces uncialis DCA2648 on solid agar medium with low titers (∼0.019mg/ L), limiting its supply by microbial fermentation and hampering its biosynthetic and engineering studies by in vivo pathway manipulation. Here we report cultivation conditions that enable genetic manipulation of UCM biosynthesis in vivo and allow UCM production, with improved titers, by submerged fermentation of the engineered S. uncialis strains. Specifically, the titer of UCM was improved nearly 58-fold to ∼1.1mg/ L through the combination of deletion of biosynthetic gene clusters encoding unrelated metabolites from the S. uncialis wild-type, chemical mutagenesis and manipulation of pathway-specific regulators to generate the engineered S. uncialis strains, and finally medium optimization of the latter for UCM production. Genetic manipulation of UCM biosynthesis was demonstrated by inactivating selected genes in the engineered S. uncialis strains, one of which afforded a mutant strain accumulating tiancimycin B, a common biosynthetic intermediate known for the anthraquinone-fused subfamily of enediyne natural products. These findings highlight a biotechnology platform for UCM biosynthesis, engineering, and production that should facilitate both its fundamental studies and translational applications.
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http://dx.doi.org/10.1093/jimb/kuab025DOI Listing
March 2021

Influence of Pelvic Intensity-Modulated Radiation Therapy With Concurrent Cisplatin-Based Chemotherapy of Cervical Cancer on the Vaginal Microbiome.

Front Oncol 2021 23;11:615439. Epub 2021 Feb 23.

Department of Radiation Oncology, The First Affiliated Hospital of Guangxi Medical University, Nanning, China.

Pelvic intensity-modulated radiation therapy (IMRT) combined with concurrent chemotherapy is an effective treatment for cervical cancer; however, radiation resistance impairs its clinical benefit. The vaginal microbiome plays an important but poorly understood role in cancer radiochemotherapy. In this study, we investigated the effects of treatment on the overall composition and alteration of the vaginal microbiome in patients receiving pelvic IMRT with concurrent cisplatin-based chemotherapy. We collected samples from twenty patients with cervical cancer and six healthy controls and performed 16S rRNA sequencing. Vaginal microbial composition analysis revealed significant differences between the two groups, but no significant differences between radiation treatment time points. However, the relative abundances of , and the increased with time. The results encourage further study into the effects of the vaginal microbiome on cervical cancer treatment strategies, especially radiochemotherapy. Better understanding of these effects could inform new therapeutic approaches to enhance the efficacy of radiochemotherapy.
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http://dx.doi.org/10.3389/fonc.2021.615439DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7940522PMC
February 2021

Targeting neutrophils as a novel therapeutic strategy after stroke.

J Cereb Blood Flow Metab 2021 Mar 10:271678X211000137. Epub 2021 Mar 10.

Department of Anesthesiology, State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Stroke is followed by an intricate immune interaction involving the engagement of multiple immune cells, including neutrophils. As one of the first responders recruited to the brain, the crucial roles of neutrophils in the ischemic brain damage are receiving increasing attention in recent years. Notably, neutrophils are not homogenous, and yet there is still a lack of full knowledge about the extent and impact of neutrophil heterogeneity. The biological understanding of the neutrophil response to both innate and pathological conditions is rapidly evolving as single-cell-RNA sequencing uncovers overall neutrophil profiling across maturation and differentiation contexts. In this review, we scrutinize the latest research that points to the multifaceted role of neutrophils in different conditions and summarize the regulatory signals that may determine neutrophil diversity. In addition, we list several potential targets or therapeutic strategies targeting neutrophils to limit brain damage following ischemic stroke.
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http://dx.doi.org/10.1177/0271678X211000137DOI Listing
March 2021

RIP3 facilitates necroptosis through CaMKII and AIF after intracerebral hemorrhage in mice.

Neurosci Lett 2021 04 1;749:135699. Epub 2021 Feb 1.

Key Laboratory of Non-coding RNA Transformation Research of Anhui Higher Education Institutes, Wannan Medical College, Wuhu, 241001, Anhui, China; Non-coding RNA Research Center of Wannan Medical College, Wuhu, 241001, Anhui, China. Electronic address:

Background: Necroptosis-induced neuronal damage after intracerebral hemorrhage (ICH) has been documented recently. Previous studies have reported that RIP3 and its complex are recognized as central mediators of necroptosis. In this study, the role of RIP3 in the activation of CaMKII and AIF was investigated.

Methods: We induced ICH in C57BL/6 mice by injecting collagenase IV into the basal ganglia. ICH mice were pretreated with the mPTP inhibitor CsA and the CAMKII inhibitor Kn-93, RIP3 siRNA or RIP3 rAAV. Brain edema and neurobehavior were evaluated. The expression of RIP3, p-MLKL, AIF, and CaMKII proteins was evaluated by western blotting, immunofluorescence (IF) and immunoprecipitation (IP).

Results: Significant increases in RIP3, p-MLKL, CaMKII and AIF expression were observed in ICH mice, and RIP3-AIF colocalized in the nucleus. Overexpression of RIP3 by rAAV upregulated AIF expression in both the cytoplasm and nucleus, while CaMKII expression was increased in the cytoplasm. The interaction of RIP3-AIF and RIP3-CaMKII was detected after ICH injury. These complexes were inhibited by CsA with Kn-93 or RIP3 siRNA pretreatment, which reduced brain edema and neurological deficits.

Conclusions: Our findings revealed that ICH induced necroptotic neuronal death through the RIP3-CaMKII complex and the RIP3-AIF signaling pathway. Moreover, blockade of mPTP opening could suppress the pathogenesis of necroptosis.
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http://dx.doi.org/10.1016/j.neulet.2021.135699DOI Listing
April 2021

The gut microbiota metabolite propionate ameliorates intestinal epithelial barrier dysfunction-mediated Parkinson's disease via the AKT signaling pathway.

Neuroreport 2021 02;32(3):244-251

Department of Neurology, The Affiliated Wujin Hospital of Jiangsu University, The Wujin Clinical College of Xuzhou Medical University, Changzhou, Jiangsu, China.

Objective: Parkinson's disease is a common neurodegenerative disease. Here, we investigated the protective effect and potential mechanisms of propionate on the intestinal epithelial barrier in mice with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson's disease.

Methods: Gas chromatography was used to determine short-chain fatty acids (SCFA) concentrations in the fecal samples of Parkinson's disease patients and healthy controls. The stepping test was used to analyze forelimb akinesia, whisker test was used to analyze sensorimotor injury, cylinder test was used to analyze sensorimotor function, and Western blotting was used to analyze protein expression.

Results: The concentrations of SCFAs, including acetate, butyrate and propionate, were significantly downregulated in the fecal samples of Parkinson's disease patients, and among the SCFAs, propionate decreased the most. Propionate administration improved the stepping test score, whisker test score and cylinder test score of MPTP-induced Parkinson's disease mice. Additionally, propionate administration increased the protein expression of zonula occludens-1 and occludin. Moreover, the effects of propionate on motor behavior and the intestinal epithelial barrier were dependent on the proteirrserinc-threonine kinases (AKT) signaling pathway. More importantly, treatment with SC79, a specific AKT agonist, abolished the effects of propionate on the intestinal epithelial barrier and motor behavior.

Conclusion: Our results demonstrated that propionate, which was decreased in the fecal samples of Parkinson's disease patients, exerted beneficial effects on intestinal epithelial barrier function and improved motor behavior in MPTP-induced Parkinson's disease mice through the AKT signaling pathway.
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http://dx.doi.org/10.1097/WNR.0000000000001585DOI Listing
February 2021

NOTCH3, a crucial target of miR-491-5p/miR-875-5p, promotes gastric carcinogenesis by upregulating PHLDB2 expression and activating Akt pathway.

Oncogene 2021 Mar 15;40(9):1578-1594. Epub 2021 Jan 15.

Department of Anatomical and Cellular Pathology, State Key Laboratory of Translational Oncology, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong SAR, PR China.

Aberrant Notch activation has been implicated in multiple malignancies and the identification of NOTCH receptors and related pathways is critical for targeted therapy. In this study, we aim to delineate the most prominent dysregulated NOTCH receptor and comprehensively reveal its deregulation in gastric cancer (GC). In the four Notch members, NOTCH3 was found uniformly upregulated and associated with poor clinical outcomes in multiple GC datasets. siRNA-mediated NOTCH3 knockdown demonstrated antitumor effects by suppressing cell proliferation, inhibiting monolayer formation, and impairing cell invasion abilities. Its depletion also induced early and late apoptosis. NOTCH3 was confirmed to be a direct target of two tumor suppressor microRNAs (miRNAs), namely miR-491-5p and miR-875-5p. The activation of NOTCH3 is partly due to the silence of these two miRNAs. Through RNA-seq profiling and functional validation, PHLDB2 was identified as a potent functional downstream modulator for NOTCH3 in gastric carcinogenesis. PHLDB2 expression demonstrated a positive correlation with NOTCH3, but was negatively correlated with miR-491-5p. Akt-mTOR was revealed as the downstream signaling of PHLDB2. The NOTCH3-PHLDB2-Akt co-activation was found in 33.7% GC patients and the activation of this axis predicted poor clinical outcome. GC cells treated with siNOTCH3, siPHLDB2, miR-491-5p, miR-875-5p, were more sensitive to Cisplatin and 5-FU. Taken together, the NOTCH3-PHLDB2-Akt cascade plays oncogenic role in gastric carcinogenesis and serves as a therapeutic target. Our study provided insights into Notch-mediated underlying molecular mechanisms and implied translational potential.
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http://dx.doi.org/10.1038/s41388-020-01579-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7932926PMC
March 2021

P-cresol degradation through Fe(III)-EDDS/HO Fenton-like reaction enhanced by manganese ion: Effect of pH and reaction mechanism.

Chemosphere 2021 Apr 27;269:129436. Epub 2020 Dec 27.

State Key Laboratory Base for Eco-Chemical Engineering in College of Chemical Engineering, Qingdao University of Science and Technology, Qingdao, 266042, China. Electronic address:

P-cresol is a highly toxic phenolic pollutant in coal chemical wastewater. The effective removal of p-cresol is of great significance to the ecological environment. In this study, the degradation of p-cresol by the Fe(III)-EDDS/HO Fenton-like reaction modified by Mn was investigated. The results showed that the removal rate of p-cresol could be significantly increased by the addition of Mn under neutral and weakly alkaline conditions (pH 6.5-8.5). Acidic conditions (pH 3.5) were not conducive to the Fenton-like reaction. This is because a neutral or weakly alkaline environment is conducive to Mn-EDDS complex formation, which can produce O to accelerate the reduction of Fe(III), and the efficiency of p-cresol degradation through a Fenton-like reaction catalyzed by the Fe(III)-EDDS complex is significantly improved. In addition, the degradation of EDDS through ·OH was reduced by O, which maintained and stabilized the Mn-EDDS complex and Fe(III)-EDDS complex. Under neutral conditions, the optimal dosage of Fe(III) is 0.7 mM, and the optimal molar ratios are EDDS/Fe(III) = 1: 1, Mn/Fe(III) = 1: 1, and HO/Fe(III) = 15: 1. The addition of free radical clearance isopropanol and CHCl proved that ·OH was the main active substance in the p-cresol degradation process.
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http://dx.doi.org/10.1016/j.chemosphere.2020.129436DOI Listing
April 2021

A Positive Feedback Loop of AKR1C3-Mediated Activation of NF-κB and STAT3 Facilitates Proliferation and Metastasis in Hepatocellular Carcinoma.

Cancer Res 2021 03 23;81(5):1361-1374. Epub 2020 Dec 23.

State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.

AKR1C3 is an enzyme belonging to the aldo-ketoreductase family, the members of which catalyze redox transformations involved in biosynthesis, intermediary metabolism, and detoxification. AKR1C3 plays an important role in tumor progression and metastasis, however, little is known about the function and the molecular mechanism underlying the role of AKR1C3 in hepatocellular carcinoma (HCC). In this study, we report that AKR1C3 is significantly upregulated in HCC and that increased AKR1C3 is associated with poor survival. AKR1C3 positively regulated HCC cell proliferation and metastasis and . AKR1C3 promoted tumor proliferation and metastasis by activating NF-κB signaling. Furthermore, AKR1C3 regulated NF-κB activity by modulating TRAF6 and inducing its autoubiquitination in HCC cells. Activation of NF-κB released proinflammatory factors that facilitated the phosphorylation of STAT3 and increased tumor cell proliferation and invasion. Gain- and loss-of-function experiments showed that AKR1C3 promoted tumor proliferation and invasion via the IL6/STAT3 pathway. STAT3 also directly bound the AKR1C3 promoter and increased transcription of AKR1C3, thereby establishing a positive regulatory feedback loop. Treatment with the AKR1C3 inhibitors indocin and medroxyprogesterone acetate inhibited tumor growth and invasion and promoted apoptosis in HCC cells. Collectively, these results indicate that a AKR1C3/NF-κB/STAT3 signaling loop results in HCC cell proliferation and metastasis and could be a promising therapeutic target in HCC. SIGNIFICANCE: These findings elucidate a novel AKR1C3-driven signaling loop that regulates proliferation and metastasis in HCC, providing potential prognostic and therapeutic targets in this disease.
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http://dx.doi.org/10.1158/0008-5472.CAN-20-2480DOI Listing
March 2021

Evaluation of Procalcitonin and C-reactive Protein in Early Differential Diagnosis of Neonatal Jaundice.

Clin Lab 2020 Dec;66(12)

Background: The purpose of this study was to investigate the clinical value of procalcitonin (PCT) and C-reactive protein (CRP) in the differential diagnosis of neonatal jaundice.

Methods: Eighty-five cases of neonatal jaundice in our hospital from January 2016 to March 2019 were selected as research subjects, including 30 cases of physiological jaundice, 23 cases of infectious jaundice, and 32 cases of he-molytic jaundice. Five milliliters of non-anticoagulated venous peripheral blood and 3 mL EDTA-K+ anticoagulated venous peripheral blood were sampled from each newborn when the symptoms of jaundice occurred. The non-anticoagulated blood samples were then centrifuged at 3,500 rpm for 7 minutes and the serum was used for PCT and bilirubin examinations, and the anticoagulated blood samples were prepared for CRP examination. Receiver operating characteristic (ROC) curve analysis was performed for the evaluation of differential diagnosis of neonatal jaundice by PCT, CRP, and bilirubin levels.

Results: Analyses of variance showed the postnatal age of jaundice occurring in the physiological jaundice group was older than those in the infectious jaundice and hemolytic jaundice groups (p < 0.001), and the PCT and CRP levels in the infectious jaundice group were higher than those in the hemolytic jaundice and physiological jaundice groups (p < 0.001). Pearson's correlation analysis indicated that the levels of PCT and CRP were negatively correlated with postnatal age in the physiological jaundice group (p < 0.05). ROC curve analysis demonstrated that PCT and CRP had the highest differential diagnosis efficacy of neonatal pathological and neonatal physiological jaundice with PCT and CRP at 0.70 µg/L and 8.50 mg/L, respectively, as well as the highest differential diagnosis efficacy of neonatal infectious jaundice and neonatal hemolytic jaundice with PCT and CRP at 1.84 µg/L and 13.50 mg/L, respectively.

Conclusions: This study suggested that PCT and CRP possessed important clinical values in the differential diagnosis of neonatal jaundice, and PCT was superior to the differential diagnosis of neonatal infectious jaundice.
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http://dx.doi.org/10.7754/Clin.Lab.2020.200330DOI Listing
December 2020

Intake of Alcohol and Tea and Risk of Nasopharyngeal Carcinoma: A Population-Based Case-Control Study in Southern China.

Cancer Epidemiol Biomarkers Prev 2021 Mar 10;30(3):545-553. Epub 2020 Dec 10.

Department of Cancer Prevention Center, Sun Yat-sen University Cancer Center, Guangzhou, China.

Background: The potential effect of alcohol or tea intake on the risk of nasopharyngeal carcinoma (NPC) remains controversial.

Methods: In a population-based case-control study in southern China, we assessed alcohol or tea intake from 2,441 histopathologically confirmed NPC cases and 2,546 controls. We calculated mean daily ethanol (g/day) and tea intake (mL/day). Fully adjusted ORs with 95% confidence intervals (CI) were estimated using logistic regression; potential dose-response trends were evaluated using restricted cubic spline analysis.

Results: Compared with nondrinkers, no significantly increased NPC risk in men was observed among current alcohol drinkers overall (OR, 1.08; 95% CI, 0.93-1.25), nor among current heavy drinkers (OR for ≥90 g/day ethanol vs. none, 1.32; 95% CI, 0.95-1.84) or former alcohol drinkers. Current tea drinking was associated with a decreased NPC risk (OR, 0.73; 95% CI, 0.64-0.84). Compared with never drinkers, those with the low first three quintiles of mean daily current intake of tea were at significantly lower NPC risk (OR, 0.53, 0.68, and 0.65, respectively), but not significant for the next two quintiles. Current daily tea intake had a significant nonlinear dose-response relation with NPC risk.

Conclusions: Our study suggests no significant association between alcohol and NPC risk. Tea drinking may moderately reduce NPC risk, but the lack of a monotonic dose-response association complicates causal inference.

Impact: Tea drinking might be a healthy habit for preventing NPC. More studies on biological mechanisms that may link tea with NPC risk are needed.
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http://dx.doi.org/10.1158/1055-9965.EPI-20-1244DOI Listing
March 2021

A novel streptonigrin type alkaloid from the CGMCC 4.1223 mutant Δ.

Nat Prod Res 2020 Dec 7:1-9. Epub 2020 Dec 7.

State Key Laboratory of Microbial Metabolism, Joint International Research Laboratory on Metabolic & Developmental Sciences, School of Life Sciences & Biotechnology, Shanghai Jiao Tong University, Shanghai, China.

Streptonigrin (STN) is a highly functionalized aminoquinone alkaloid with broad and potent antitumor activities. Previously, the biosynthetic gene cluster of STN was identified in CGMCC 4.1223, revealing an α/β-hydrolase (StnA) and a methyltransferase (StnQ2). In this work, a double mutant Δ was constructed by genetic manipulation and produced a novel derivative of STN, named as streptonigramide. Structure of streptonigramide was established by spectroscopic analyses. Its biosynthetic pathway has been proposed as well.
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http://dx.doi.org/10.1080/14786419.2020.1856840DOI Listing
December 2020

Landscapes of bacterial and metabolic signatures and their interaction in major depressive disorders.

Sci Adv 2020 Dec 2;6(49). Epub 2020 Dec 2.

The National Clinical Research Center for Mental Disorders & Beijing Key Laboratory of Mental Disorders, Beijing Anding Hospital, Capital Medical University, Beijing 100088, China.

Gut microbiome disturbances have been implicated in major depressive disorder (MDD). However, little is known about how the gut virome, microbiome, and fecal metabolome change, and how they interact in MDD. Here, using whole-genome shotgun metagenomic and untargeted metabolomic methods, we identified 3 bacteriophages, 47 bacterial species, and 50 fecal metabolites showing notable differences in abundance between MDD patients and healthy controls (HCs). Patients with MDD were mainly characterized by increased abundance of the genus and decreased abundance of the genera and These multilevel omics alterations generated a characteristic MDD coexpression network. Disturbed microbial genes and fecal metabolites were consistently mapped to amino acid (γ-aminobutyrate, phenylalanine, and tryptophan) metabolism. Furthermore, we identified a combinatorial marker panel that robustly discriminated MDD from HC individuals in both the discovery and validation sets. Our findings provide a deep insight into understanding of the roles of disturbed gut ecosystem in MDD.
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http://dx.doi.org/10.1126/sciadv.aba8555DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7710361PMC
December 2020

[A modified gentamicin protection assay for detecting invasive phenotype of Salmonella enterica serovar Enteritidis].

Sheng Wu Gong Cheng Xue Bao 2020 Nov;36(11):2459-2466

School of Life Sciences, Ludong University, Yantai 264025, Shandong, China.

Salmonella enterica serovar Enteritidis (SE) is one of the most important zoonotic pathogens that cause enteritis and systemic infection in animals and human. Understanding invasive capacities of SE isolates is of vital importance to elucidate pathogenesis of Salmonella infection. To improve the throughput capacity and repeatability of classical gentamicin protection assay (GPA), a modified PGA was developed by taking high-throughput advantage of 96-well cell plates and multichannel pipettes. In addition, drop plate technique rather than spread plate method was applied in the modified GPA protocol for bacterial enumeration. The modified GPA protocol was evaluated by phenotyping intracellular replication of a high virulent and a low virulent SE isolates, JL228 and LN248, in a phagocytic cell line RAW264.7. The protocol was then applied in invasive phenotype determination of 16 SE strains to non-phagocytes (HT-29) and the intracellular replication of 43 SE strains to phagocytes (RAW264.7). Significant lower intra-group and inter-group coefficient of variations of the modified GPA was observed, implying good repeatability and reproducibility over traditional protocol. Further, replication phenotypes were also correlated with those from direct observation by confocal microscopy. Collectively, the improved GPA protocol had advantages of high throughput capacity, good repeatability and reliability, it was also noticed that the protocol also represented a fast and labor-saving alternative scheme for the invasive phenotype determination of Salmonella Enteritidis, and providing reliable phenotype profiles for Salmonella-host interplay interpretation.
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http://dx.doi.org/10.13345/j.cjb.200171DOI Listing
November 2020

Neutrophil Surface CD64 Stimulation Index Detection Assay in Diagnosing Mycobacterium tuberculosis Infection.

Clin Lab 2020 Nov;66(11)

Background: This study aimed to develop a method for assessing the sensitivity and diagnostic performance of the neutrophil surface CD64 stimulation index (SI) in tuberculosis infection.

Methods: A total of 149 samples were divided into three groups (tuberculosis group, n = 51; nontuberculosis infection group, n = 50; and healthy control group, n = 48). Flow cytometry was used to detect the sensitivity of CD64 SI on the surface of neutrophils. The sensitivities of CD64 SI before and after stimulation with ESAT-6 and CFP-10 antigens were compared using interferon-gamma release assay-enzyme-linked immunosorbent assay (IGRA-ELISA).

Results: The diagnostic threshold for CD64 SI based on the receiver operating characteristic curve was found to be 2.025, which is the standard for judging tuberculosis infection. The IGRA-ELISA and the CD64 SI assays were highly consistent with a kappa value of 0.635 (p < 0.003, 95% CI: 0.002 - 0.003).

Conclusions: The neutrophil surface CD64 SI value detection method may serve as one of the new diagnostic methods for active Mycobacterium tuberculosis infection.
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http://dx.doi.org/10.7754/Clin.Lab.2020.200214DOI Listing
November 2020

Pyrotinib enhances the radiosensitivity of HER2‑overexpressing gastric and breast cancer cells.

Oncol Rep 2020 Dec 21;44(6):2634-2644. Epub 2020 Oct 21.

Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China.

The overexpression or amplification of HER2 has been observed in a significant proportion of both gastric cancer (GC) and breast cancer (BC) cases. Pyrotinib is an irreversible dual (EGFR/HER2) tyrosine kinase inhibitor (TKI), newly evaluated for the treatment of HER2‑overexpressing cancer types. As radiotherapy (RT) serves a crucial role in controlling the local recurrence of GC and BC, the present study investigated the impact of pyrotinib on the irradiation response. The current results demonstrated that pyrotinib enhanced the radiosensitivity of HER2‑overexpressing GC and BC cells in vitro and in vivo. In both NCI‑N87 and SKBR3 cells, pyrotinib suppressed the irradiation‑induced HER2 nuclear transport. Furthermore, pyrotinib increased DNA damage induced by irradiation in both cancer cell lines. Pyrotinib also enhanced the cytotoxicity of docetaxel, which may provide a novel strategy for potential drug combinations. Thus, pyrotinib is a promising irradiation sensitizer in patients with HER2‑overexpressing GC and BC. The present results provide a theoretical foundation for further clinical evaluation of pyrotinib.
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http://dx.doi.org/10.3892/or.2020.7820DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7640366PMC
December 2020

Inhibition of miR-188-5p Suppresses Progression of Experimental Abdominal Aortic Aneurysms.

J Cardiovasc Pharmacol 2021 01;77(1):107-114

Departments of Vascular Surgery; and.

Abstract: Abdominal aortic aneurysm (AAA) is an aging-related degenerative disease. miR-188-5p was reported to induce cell senescence and play a key role in aging-related disease. Therefore, in this study, we investigated miR-188-5p expression during progression in experimental AAAs. Furthermore, we investigated whether inhibition of miR-188-5p could suppress AAA progression. Experimental AAAs were created in 9-12-week-old male C57BL/6J mice by transient intra-aortic infusion of porcine pancreatic elastase. Expression of miR-188-5p levels were assessed in aneurysmal and control aortae during the progression of aneurysm. For inhibition experiment, miR-188 inhibiting group mice were injected with AAV2-miR188-5p sponge through tail vein and control group mice were injected with AAV2-CMV-GFP. Influences on experimental AAA progression were assessed by measurements of aortic diameter and histopathologic analysis at sacrifice. Meanwhile, immunohistochemistry and fluorescence in situ hybridization were used to determine the inflammatory cells infiltration and colocalization of miR-188-5p in aortic sections. Expression of miR-188-5p is upregulated during progression of AAA. Importantly, miR-188-5p inhibition treatment prevented enlargement of experimental aneurysms. Meanwhile, miR-188-5p inhibition regimens attenuated medial elastin degradation, smooth muscle cell depletion, and mural angiogenesis and the accumulation of macrophages, T cells, and angiogenesis. Furthermore, colocalization of miR188-5p with CD68 and CD3 was observed, which suggest miR-188-5p was expressed mainly in infiltrated macrophages and T cells. Expression of miR-188-5p is increased in experimental AAAs. Treatment with miR-188-5p inhibition limits experimental AAA progression, with histologic evidence of reduced neovessels and attenuated mural leukocyte infiltration. These findings underscore the potential significance of miR-188-5p in aneurysm pathogenesis and as a target for suppression of AAA disease.
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http://dx.doi.org/10.1097/FJC.0000000000000915DOI Listing
January 2021

Apatinib exhibits synergistic effect with pyrotinib and reverses acquired pyrotinib resistance in HER2-positive gastric cancer via stem cell factor/c-kit signaling and its downstream pathways.

Gastric Cancer 2021 Mar 8;24(2):352-367. Epub 2020 Oct 8.

Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, 430030, Hubei, China.

Background: Recently, progress has been made in the development of targeted therapies for human epidermal growth factor receptor 2 (HER2)-positive gastric cancer (GC). However, drug resistance has severely limited the efficacy of anti-HER2 therapies. Pyrotinib is a novel pan-HER inhibitor. Although it is effective in HER2-positive GC treatment, its efficacy in combination with apatinib and associated resistance mechanisms in HER2-positive GC remains unclear.

Methods: In this study, the combination effects of pyrotinib and apatinib were examined in two pyrotinib-sensitive GC cells and xenografts. The RNA sequencing was used to determine the underlying mechanisms of acquired pyrotinib resistance. The role of imatinib and apatinib in reversing pyrotinib resistance was tested in pyrotinib-resistant cells and xenografts.

Results: Here, we reported that a combination of pyrotinib and apatinib exhibits synergistic effect in HER2-positive NCI-N87 xenografts, and showed enhanced antitumor efficacy in HER2-positive GC, both in vitro and in vivo. Moreover, up-regulation of the stem cell factor (SCF) levels, and the PI3K/AKT and MAPK pathways was associated with acquired pyrotinib resistance in HER2-positive GC. Mechanistically, we demonstrated that the activation of the SCF/c-kit signaling and its downstream PI3K/AKT and MAPK pathways mediated pyrotinib resistance by promoting cell survival and proliferation. Imatinib and apatinib augmented the sensitivity of pyrotinib-resistant cells and xenografts to pyrotinib, by blocking SCF/c-kit signaling.

Conclusion: These results highlight the effectiveness of pyrotinib combined with apatinib in HER2-positive GC and acquired pyrotinib resistance, thus providing a theoretical basis for new treatment methods.
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http://dx.doi.org/10.1007/s10120-020-01126-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7902570PMC
March 2021

A prediction model to evaluate the pretest risk of malignancy in solitary pulmonary nodules: evidence from a large Chinese southwestern population.

J Cancer Res Clin Oncol 2021 Jan 6;147(1):275-285. Epub 2020 Oct 6.

Department of Respiratory and Critical Care Medicine, West China Hospital of Sichuan University, No. 37, Guo Xue Alley, Chengdu, 610041, Sichuan, China.

Purpose: Lung cancer is the leading cause of cancer death and there have been clinical prediction models. This study aimed to evaluate the diagnostic performance of published models and create new models to evaluate the probability of malignant solitary pulmonary nodules (SPNs) in Chinese population.

Methods: We consecutively enrolled 2061 patients with SPNs from West China Hospital between January 2008 and December 2016, each SPN was pathologically confirmed. First, four published prediction models, Mayo clinic model, Veterans Affairs (VA) model, Brock model and People's Hospital of Peking University (PEH) model were validated in our patients. Then, utilizing logistic regression, decision tree and random forest (RF), we developed three new models and internally validated them.

Results: Area under the receiver operating characteristic curve (AUC) values of four published models were as follows: Mayo 0.705 (95% CI 0.658-0.752, n = 726), VA 0.64 6 (95% CI 0.598-0.695, n = 800), Brock 0.575 (95% CI 0.502-0.648, n = 550) and PEH 0.675 (95% CI 0.627-0.723, n = 726). Logistic regression model, decision tree model and RF model were developed, AUC values of these models were 0.842 (95% CI 0.778-0.906), 0.734 (95% CI 0.647-0.821), 0.851 (95% CI 0.789-0.914), respectively.

Conclusion: The four published lung cancer prediction models do not apply to our population, and we have established new models that can be used to predict the probability of malignant SPNs.
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http://dx.doi.org/10.1007/s00432-020-03408-2DOI Listing
January 2021

The Most Cited Original Articles in Brain Imaging of Children With Cerebral Palsy: A Bibliometric Analysis Between 1984 and 2019.

Front Neurol 2020 8;11:955. Epub 2020 Sep 8.

Department of Radiology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.

Brain imaging is important in diagnosing children with cerebral palsy (CP) and in identifying its etiology. To provide study navigation in this field, a bibliometric analysis was conducted by analyzing the most highly cited articles. The Web of Science All Databases were used for literature search in this study. All original articles on imaging in children with CP were searched. Two reviewers screened the search results independently and eliminated articles based on exclusion criteria such as participants over 20 years old, topics referring to images outside of the brain, or trauma. According to descending order of yearly citation counts, the top 25% of all included articles were considered as highly cited articles. Information such as yearly citations, research purposes, imaging modalities, CP types, and study designs were recorded and analyzed. A total of 50 highly cited articles ranked by yearly citations (from 23.85 to 3.33, 1991-2018) were included in this study. Considering different research purposes, these studies were classified into three categories: diagnosis studies ( = 25; 1991-2017, median: 2011), mechanism studies ( = 15; 1999-2018; median: 2014), and prognosis and therapeutic effect studies ( = 10; 2008-2017; median: 2014.5). First, for diagnosis studies, 22 studies used single modality and three used multi-modalities; the majority of these studies focused on diagnostic value evaluation ( = 10) and image performance ( = 12) of a single type of CP ( = 15) by using descriptive ( = 14) or cross-sectional approaches ( = 10). Second, for mechanism studies, the ratio between single and multi-modality was 8:7; most of these studies concentrated on a single subtype of spastic CP (hemiplegia = 10, quadriplegia = 2) with a cross-sectional study design ( = 10). Third, regarding the prognosis and therapeutic effect studies, the single vs. multi-modality ratio was 5:5, and these studies were dedicated to the efficiency of constraint-induced movement therapy in children with hemiplegia; paired design trials ( = 6) and randomized controlled trials ( = 2) were used more frequently. Studies using multi-modality and high-level evidence-based design to provide information regarding mechanism, prognosis, and therapeutic efficacy may be the potential future research direction in the field of CP research.
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http://dx.doi.org/10.3389/fneur.2020.00955DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7508001PMC
September 2020

Evolution from Tunneling to Hopping Mediated Triplet Energy Transfer from Quantum Dots to Molecules.

J Am Chem Soc 2020 10 2;142(41):17581-17588. Epub 2020 Oct 2.

Department of Chemistry, University of California, Riverside, Riverside, California 92521, United States.

Efficient energy transfer is particularly important for multiexcitonic processes like singlet fission and photon upconversion. Observation of the transition from short-range tunneling to long-range hopping during triplet exciton transfer from CdSe nanocrystals to anthracene is reported here. This is firmly supported by steady-state photon upconversion measurements, a direct proxy for the efficiency of triplet energy transfer (TET), as well as transient absorption measurements. When phenylene bridges are initially inserted between a CdSe nanocrystal donor and anthracene acceptor, the rate of TET decreases exponentially, commensurate with a decrease in the photon upconversion quantum efficiency from 11.6% to 4.51% to 0.284%, as expected from a tunneling mechanism. However, as the rigid bridge is increased in length to 4 and 5 phenylene units, photon upconversion quantum efficiencies increase again to 0.468% and 0.413%, 1.5-1.6 fold higher than that with 3 phenylene units (using the convention where the maximum upconversion quantum efficiency is 100%). This suggests a transition from exciton tunneling to hopping, resulting in relatively efficient and distance-independent TET beyond the traditional 1 nm Dexter distance. Transient absorption spectroscopy is used to confirm triplet energy transfer from CdSe to transmitter, and the formation of a bridge triplet state as an intermediate for the hopping mechanism. This first observation of the tunneling-to-hopping transition for long-range triplet energy transfer between nanocrystal light absorbers and molecular acceptors suggests that these hybrid materials should further be explored in the context of artificial photosynthesis.
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http://dx.doi.org/10.1021/jacs.0c07727DOI Listing
October 2020

Correction: Upregulation of SNX5 predicts poor prognosis and promotes hepatocellular carcinoma progression by modulating the EGFR-ERK1/2 signaling pathway.

Oncogene 2020 Oct;39(41):6511

State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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http://dx.doi.org/10.1038/s41388-020-01440-7DOI Listing
October 2020

Cyclodextrin-mediated formation of porous RNA nanospheres and their application in synergistic targeted therapeutics of hepatocellular carcinoma.

Biomaterials 2020 12 7;261:120304. Epub 2020 Aug 7.

State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200032, PR China. Electronic address:

Spherical and porous nanoparticles are ideal nanostructures for drug delivery. But currently they are mainly composed of non-degradable inorganic materials, which hinder clinical applications. Here, biological porous nanospheres using RNA as the building blocks and cyclodextrin as the adhesive were synthesized. The RNA contained the aptamer of EpCAM for targeting delivery and siRNA for gene silencing of EpCAM, while cyclodextrin could load insoluble sorafenib, the core drug of targeted therapy for hepatocellular carcinoma (HCC), through its hydrophobic cavity. After being internalized into targeted HCC cells under the assistance of the aptamer, the porous nanospheres could be degraded by the cytoplasmic Dicer enzymes, releasing siRNA and sorafenib for synergistic therapy. The synergistic efficacy of the porous RNA nanospheres has been validated at in vitro function assay, subcutaneous tumor bearing mice, and orthotopic tumor bearing mice in vivo models. In view of the broad prospects of synergy of gene therapy with chemotherapy, and the fact that RNA and cyclodextrin of the porous nanospheres can be extended to load various types of siRNA and small molecule drugs, respectively, this form of biological porous nanospheres offers opportunities for targeted delivery of suitable drugs for treatment of specific tumors.
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http://dx.doi.org/10.1016/j.biomaterials.2020.120304DOI Listing
December 2020

Radiation Therapy-Induced Changes of the Nasopharyngeal Commensal Microbiome in Nasopharyngeal Carcinoma Patients.

Int J Radiat Oncol Biol Phys 2021 Jan 28;109(1):145-150. Epub 2020 Aug 28.

Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. Electronic address:

Purpose: The human commensal microbiome has been suggested to be involved in the regulation of response to anticancer therapies. However, little is known regarding changes in commensal microbes in patients with cancer during radiation therapy. We conducted a prospective, longitudinal proof-of-concept cohort study with patients with newly diagnosed nasopharyngeal carcinoma (NPC) who underwent radiation therapy-based treatment.

Methods And Materials: Nasopharyngeal swabs were collected before radiation therapy, twice per week during radiation therapy, and after radiation therapy. The nasopharyngeal microbiome was assessed using 16S rRNA amplicon sequencing. A patient's response to treatment was measured 3 months after the completion of radiation therapy as a short-term clinical outcome. In total, 39 NPC patients with 445 nasopharyngeal samples were analyzed.

Results: There was stable temporal change in the community structure of the nasopharyngeal microbiome among patients with NPC during treatment (P = .0005). Among 73 abundant amplicon sequence variants (ASVs), 7 ASVs assigned to genus Corynebacterium decreased significantly during the treatment (W-statistic >80%); 23 ASVs showed statistically significant changes in the ratio of abundance between early and late responders during treatment (false discovery rate <0.05).

Conclusions: This study addressed stable temporal change in the nasopharyngeal microbiome among patients with NPC during radiation therapy-based treatment and provided preliminary evidence of an association with a short-term clinical outcome.
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http://dx.doi.org/10.1016/j.ijrobp.2020.08.054DOI Listing
January 2021

Naphthoquinone-Based Meroterpenoids from Marine-Derived sp. B9173.

Biomolecules 2020 08 15;10(8). Epub 2020 Aug 15.

State Key Laboratory of Microbial Metabolism, and Joint International Research Laboratory on Metabolic & Developmental Sciences, and School of Life Sciences & Biotechnology, Shanghai Jiao Tong University; 800 Dongchuan Rd, Shanghai 200240, China.

Naphthoquinone-based meroterpenoids are hybrid polyketide-terpenoid natural products with chemical diversity and a broad range of biological activities. Here, we report the isolation of a group of naphthoquinone-containing compounds from sp. B9173, and their structures were elucidated by using a combination of spectroscopic techniques, including 1D, 2D NMR, and high-resolution mass (HRMS) analysis. Seven flaviogeranin congeners or intermediates, three of which were new, have been derived from common naphthoquinone backbone and subsequent oxidation, methylation, prenylation, and amino group incorporation. Both flaviogeranin B1 () and B () contain an amino group which was incorporated into the C8 of 1,3,6,8-terhydroxynaphthalene (THN). Flaviogeranin D () contains an intact -geranylgeranyl residue attached to the C2 of THN, while the -geranylgeranyl group of links with the hydroxyl on the C2 site of THN. Four compounds were selected and tested for antibacterial activity and cytotoxicity, with and flaviogeranin C2 () displaying potent activity against selected bacteria and cancer cell lines. In light of the structure features of isolated compounds and the biosynthetic genes, a biosynthetic pathway of naphthoquinone-based flaviogeranins has been proposed. These isolated compounds not only extend the structural diversity but also represent new insights into the biosynthesis of naphthoquinone-based meroterpenoids.
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http://dx.doi.org/10.3390/biom10081187DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7463872PMC
August 2020