Publications by authors named "Zhe Ma"

172 Publications

Active Components from Traditional Herbal Medicine for the Potential Therapeutics of Idiopathic Pulmonary Fibrosis: A Systemic Review.

Am J Chin Med 2021 Jun 3:1-22. Epub 2021 Jun 3.

State Key Laboratory of Component-Based Chinese Medicine, Tianjin 301617, P. R. China.

Idiopathic pulmonary fibrosis (IPF), a tumor-like disease, is a serious and fatal pulmonary inflammatory condition usually characterized by irreversible destruction of the lung parenchyma, excessive matrix accumulation, and decline in lung function. IPF still remains a great burden to the universe. At the moment, the available therapeutic regimens utilized for IPF such as non-pharmacological therapies (lung transplantation) and pharmacological therapies (drugs, nintedanib, pirfenidone, etc.) are normally accompanied by significant limitations, such as adverse reactions, low bioavailability, poor selectivity, low-tissue distribution, instability, systemic toxicity, inconveniency and unsafe usage. There is a need for the exploration and discovery of new novel remedies by researchers and scientists globally. Recent numerous preliminary studies have laid significant emphasis and demonstrated the antifibrotic importance, good curative actions (little or no adverse reactions), and multiple target sites of the active components from traditional herbal medicine (THM) against IPF, which could serve as a modern, alternative and potential therapeutics or drug candidates in treating IPF. This paper extensively summarizes the pharmacological actions and signaling pathways or mechanisms of active components obtained from THM for treating IPF. Moreover, the sources and modernization, markets, relevant FDA and CFDA studies (the USA and China), preclinical analysis, and various compositions of THM currently under clinical trials are also highlighted. Additionally, this present analytical data would be instrumental towards further drug progression or advancement of active components from THM for the potential therapeutics of IPF in the future.
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http://dx.doi.org/10.1142/S0192415X2150052XDOI Listing
June 2021

Circular RNA circSMARCA5 is a prognostic biomarker in patients with malignant tumor: a meta-analysis.

BMC Cancer 2021 May 25;21(1):600. Epub 2021 May 25.

Department of Urology, Jinshan Hospital, Fudan University, Shanghai, 201508, China.

Background: Malignant tumor is one of the most serious diseases endangering human health. Circular RNAs play an important role in the tumorigenesis and progression of various malignant tumors. Although various studies have investigated the biological function of circular RNA circSMARCA5 in malignant tumors, the prognostic value of circSMARCA5 in malignant tumor patients has not been systematically analyzed.

Methods: Relevant studies were obtained from the PubMed and Web of Science database. The quality of the enrolled studies was evaluated using the Newcastle-Ottawa Scale quality assessment system. Survival features and clinicopathological features were assessed using pooled hazard ratios and odds ratios with 95% confidence intervals, respectively.

Results: Overall, 7 relevant publications were enrolled in the meta-analysis. CircSMARCA5 expression was significantly correlated with better OS (HR = 0.51, 95%CI 0.41-0.65) or DFS/RFS/PFS (HR = 0.56, 95%CI 0.43-0.73) in malignant tumors. In the pooled analyses of clinicopathological characteristics, malignant tumors with higher circSMARCA5 were better differentiated (OR = 0.41, 95%CI 0.19-0.88). CircSMARCA5 expression was correlated with less advanced TNM stage (OR = 0.33, 95%CI 0.19-0.55). Moreover, malignant tumors with higher circSMARCA5 expression have less advanced lymph node metastasis (OR = 0.26, 95%CI 0.08-0.79).

Conclusion: These results indicated that circSMARCA5 was a promising biomarker in malignant tumors, which may potentially facilitate clinical decisions in the future.
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http://dx.doi.org/10.1186/s12885-021-08316-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8145840PMC
May 2021

The phosphorylation of phosphoglucosamine mutase GlmM by Ser/Thr kinase STK mediates cell wall synthesis and virulence in Streptococcus suis serotype 2.

Vet Microbiol 2021 Jul 6;258:109102. Epub 2021 May 6.

MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, Yangzhou 225009, China. Electronic address:

Streptococcus suis serotype 2 (SS2) is an important zoonotic pathogen that causes serious economic losses in the pig industry. Phosphorylation is an important mechanism of protein modification. Recent studies have reported that the serine/threonine kinase (STK) gene contributes to the growth and virulence of SS2. However, the mechanism underlying the regulatory functions of STK in SS2 has not been thoroughly elucidated to date. In this study, phosphoproteomic analysis was performed to determine substrates of the STK protein. Twenty-two proteins with different cell functions were identified as potential substrates of STK. Phosphoglucosamine mutase (GlmM) was selected for further investigation among them. In vitro phosphorylation assay and immunoprecipitation assay indicated that GlmM was phosphorylated by STK at the Ser-101 site and the phosphorylation level of GlmM can be affected. We observed that compared to the wild-type strain ZY05719, the glmM-deficient strain (ΔglmM) and the glmM S101A point mutation strain (CΔglmM S101A) showed aberrant cell morphology and attenuated virulence, including enlarged cell volume, absent capsule, decreased resistance, lower survival caused by unusual peptidoglycan synthesis, and significantly attenuated pathogenicity in a mouse infection model. Additionally, compared to ZY05719 and CΔglmM, GlmM enzyme acivities and peptidoglycan concentrations of the stk-deficient strain (Δstk), CΔglmM S101A decreased significantly. These experiments revealed that STK phosphorylates GlmM at the Ser-101 site to impact GlmM enzyme activity and control cell wall peptidoglycan synthesis to affect SS2 pathogenicity.
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http://dx.doi.org/10.1016/j.vetmic.2021.109102DOI Listing
July 2021

The II-I Phase Transition Behavior of Butene-1 Copolymers with Hydroxyl Groups.

Polymers (Basel) 2021 Apr 16;13(8). Epub 2021 Apr 16.

Tianjin Key Laboratory of Composite and Functional Materials and School of Materials Science and Engineering, Tianjin University, Tianjin 300072, China.

The crystallization and II-I phase transition of functionalized polybutene-1 with hydroxyl groups were investigated by differential scanning calorimetry. The results show that the incorporated hydroxyl groups increase the nucleation density but decrease the growth rate in melt crystallization. Interestingly, for the generated tetragonal form II, the presence of polar hydroxyl groups can effectively accelerate the phase transition into the thermodynamically stable modification of trigonal form I, especially with stepwise annealing and high incorporation. Using stepwise annealing, II-I phase transition was enhanced by an additional nucleation step performed at a relatively low temperature, and the optimal nucleation temperature to obtain the maximum transition degree was ‒10 °C, which is independent from the content of hydroxyl groups. Furthermore, the accelerating effect of hydroxyl groups on the II-I transition kinetics can be increased by reducing the crystallization temperature when preparing form II crystallites. These results provide a potential molecular design approach for developing polybutene-1 materials.
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http://dx.doi.org/10.3390/polym13081315DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8074023PMC
April 2021

Enhanced Anticancer Efficacy of Dual Drug-Loaded Self-Assembled Nanostructured Lipid Carriers Mediated by pH-Responsive Folic Acid and Human-Derived Cell Penetrating Peptide dNP2.

Pharmaceutics 2021 Apr 22;13(5). Epub 2021 Apr 22.

State Key Laboratory of Component-Based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China.

The poor ability of recognition and penetration of chemotherapeutic agents to tumor cells are still great challenges for targeted breast cancer treatment. Herein, we established a tumor-targeted nanostructured lipid carrier encapsulating gambogic acid (GA) and paclitaxel (PTX), which was co-modified with acid-cleavable folic acid (cFA) and a human-derived cell penetrating peptide dNP2 (CKIKKVKKKGRKKIKKVKKKGRK). The multi-functional nano-platform exhibited an enhanced targeting and penetrability to tumor tissues, which was accomplished by the combined action of cFA and dNP2. After intravenous injection, firstly, cFA could actively target the breast cancer tissues by the selective recognition of folate receptor (FR); then, upon arrival at the tumor microenvironment, the acid-cleavable FA and dNP2 dual modified nanostructured lipid carrier (cFA/dNP2-GA/PTX-NLC) exhibited sensitive cleavage of folic acid (FA), which could reduce the hindrance effect of FA to maximize the dNP2 cell-penetrating properties. The effect of different modification on cellular uptake, in vivo bio-distribution, and anticancer activity of NLCs proved our hypothesis that compared with NLCs modified by non-cleavable FA or a single ligand, cFA/dNP2-GA/PTX-NLC displayed more efficient intracellular delivery, stronger targeting ability in vivo, improved cytotoxicity on 4T1 cells, and produced the better therapeutic efficacy of GA and PTX. The strategy affords a feasible way to overcome the poor recognition and permeability of medicines in cancer treatment.
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http://dx.doi.org/10.3390/pharmaceutics13050600DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8143576PMC
April 2021

Rapid Responsive Mechanochromic Photonic Pigments with Alternating Glassy-Rubbery Concentric Lamellar Nanostructures.

ACS Nano 2021 May 29;15(5):8770-8779. Epub 2021 Apr 29.

Tianjin Key Laboratory of Composite and Functional Materials, School of Materials Science and Engineering, Tianjin University, Tianjin 300350, China.

Photonic pigment particles prepared self-assembly have been suffering from their poor mechanical performances; ., they can easily be damaged and lose structural color under a compression force. This greatly limits their uses as mechanochromic pigments. Here, a nanoscale concentric lamellar structure of alternating glassy-rubbery microdomains is successfully created within photonic microparticles through a confined self-assembly and photo-cross-linking strategy. The glassy domain is composed of polystyrene, and cross-linked bottlebrush polydimethylsiloxane served as the supersoft elastic domain. The obtained photonic structure not only shows large deformation and visible color changes under a loaded compression force but also rapidly recovers to its original state in less than 1 s (∼0.16 s) upon unloading. Continuously loading-unloading micro compression test indicates that no obvious damage can be identified after 250 cycles, indicating the high durability of the pigments against deformation. These pigments with different reflected colors are simply obtained using bottlebrush block copolymer formulations with tunable weight percentages of polymer additives. The mechanical robust photonic pigments may be useful in many important applications.
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http://dx.doi.org/10.1021/acsnano.1c01147DOI Listing
May 2021

Interface Bonding Behavior of Concrete-Filled Steel Tube Blended with Circulating Fluidized Bed Bottom Ash.

Materials (Basel) 2021 Mar 20;14(6). Epub 2021 Mar 20.

School of Science, North University of China, Taiyuan 030051, China.

The interface bonding behavior between the steel tube and the concrete of concrete-filled steel tube (CFST) blended with circulating fluidized bed bottom ash (CFB-BA) was investigated in this study. A total of 8 groups of CFSTs stub columns were prepared with different dosage of CFB-BA, water-binder ratio (W/B), and interface bonding length. A series of push-out tests were carried out to acquire the data representing the interface bonding behavior. The results show that the dosage of CFB-BA has a direct effect on interface bonding behavior of CFST. CFB-BA can improve the interface bonding behavior of CFST. The highest ultimate bonding load and strength are achieved when the dosage of CFB-BA is 30%. When the dosage of CFB-BA increases to 50%, its interface bonding behavior decreases, but is still better than that of CFST without CFB-BA. W/B has a negative correlation with the interface bonding behavior of CFST. While the W/B increases, the interface bonding load and strength of CFST decreases. The increase of the interface bonding length can improve the interface bonding load, but cannot improve the interface bonding strength.
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http://dx.doi.org/10.3390/ma14061529DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8004054PMC
March 2021

Novel circular RNA circSOBP governs amoeboid migration through the regulation of the miR-141-3p/MYPT1/p-MLC2 axis in prostate cancer.

Clin Transl Med 2021 Mar;11(3):e360

Department of Urology, Jinshan Hospital, Fudan University, Shanghai, P. R. China.

Background: Metastatic prostate cancer is a fatal disease despite multiple new approvals in recent years. Recent studies revealed that circular RNAs (circRNAs) can be involved in cancer metastasis. Defining the role of circRNAs in prostate cancer metastasis and discovering therapeutic targets that block cancer metastasis is of great significance for the treatment of prostate cancer.

Methods: The circSOBP levels in prostate cancer (PCa) were determined by qRT-PCR. We evaluated the function of circSOBP using a transwell assay and nude mice lung metastasis models. Immunofluorescence assay and electron microscopic assay were applied to determine the phenotypes of prostate cancer cells' migration. We used fluorescence in situ hybridization assay to determine the localization of RNAs. Dual luciferase and rescue assays were applied to verify the interactions between circSOBP, miR-141-3p, MYPT1, and phosphomyosin light chain (p-MLC2).

Results: We observed that circSOBP level was significantly lower in PCa specimens compared with adjacent noncancerous prostate specimens, and was correlated with the grade group of PCa. Overexpression of circSOBP suppressed PCa migration and invasion in vitro and metastasis in vivo. CircSOBP depletion increased migration and invasion and induced amoeboid migration of PCa cells. Mechanistically, circSOBP bound miR-141-3p and regulated the MYPT1/p-MLC2 axis. Moreover, the depletion of MYPT1 reversed the inhibitory effect of circSOBP on the migration and invasion of PCa cells. Complementary intronic Alu elements induced but were not necessary for the formation of circSOBP. The nuclear export of circSOBP was mediated by URH49.

Conclusion: Our results suggest that circSOBP suppresses amoeboid migration of PCa cells and inhibits migration and invasion through sponging miR-141-3p and regulating the MYPT1/p-MLC2 axis.
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http://dx.doi.org/10.1002/ctm2.360DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8002909PMC
March 2021

Human immune deficiency virus-related structural alterations in the brain are dependent on age.

Hum Brain Mapp 2021 Jul 23;42(10):3131-3140. Epub 2021 Mar 23.

School of Biological Science and Medical Engineering, Beihang University, Beijing, China.

Currently, it is still unknown whether human immune deficiency virus (HIV)-related structural alterations in the brain are dependent on age. With people living with HIV at different ages, we aim to investigate age-specific structural alterations in HIV patients. Eighty-three male HIV patients and eighty-three age-matched male controls were enrolled, and high-resolution T1 weighted images were collected and analyzed with four morphological metrics. Then, statistical analyses were respectively conducted to ascertain HIV effects, age effects, and medication effects in brain structure of HIV patients, and the relationship with neuropsychological evaluations were further explored. Finally, discriminative performances of these structural abnormalities were quantitatively testified with three machine learning models. Compared with healthy controls, HIV patients displayed lower gray matter volumes (GMV), lower gyrification index, deeper sulcus depth, and larger cortical thickness (CTH). Age-specific differences were found in GMV and CTH: young-aged HIV patients displayed more obvious morphological alterations than middle-aged HIV patients when comparing corresponding age-matched healthy controls. Furthermore, age-specific long-term medication effect of combination antiretroviral therapy were also presented. Additionally, several subcortical structural changes were negatively associated with language, attention and motor functions. Finally, three machine learning models demonstrated young-aged HIV patients were easier to be recognized than middle-aged HIV patients. Our study indicated young-aged HIV patients were more vulnerable to HIV infection in brain structure than middle-aged patients, and future studies should not ignore the age effect in studying the HIV-related abnormalities.
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http://dx.doi.org/10.1002/hbm.25423DOI Listing
July 2021

Protocol for Monitoring DNA-Triggered cGAS/STING Signaling in Mammalian Cells and Mice.

STAR Protoc 2020 Dec 14;1(3):100171. Epub 2020 Nov 14.

Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.

Innate immunity is the first layer of defense against infection in mammals and is tightly regulated. We monitored cGAS/STING signaling upon ISD90 or 2',3'-cGAMP stimulation in EA.hy926 cells by western blotting, RT-PCR, and ELISA analyses to reveal signaling activation and IFNβ production. In addition, we also include an HSV-1 infected mouse model to further reveal procedures in analyzing cGAS/STING signaling in mice. This protocol could be applied to studies focusing on cell culture or mouse models to investigate cGAS/STING signaling. For complete details on the use and execution of this protocol, please refer to Zhang et al. (2020).
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http://dx.doi.org/10.1016/j.xpro.2020.100171DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7757363PMC
December 2020

GPU-based fast processing for a distributed acoustic sensor using an LFM pulse.

Appl Opt 2020 Dec;59(35):11098-11103

We carried out a fast processing investigation based on a graphics processing unit (GPU) for a distributed acoustic sensor using a linear frequency modulation pulse. The moving window cross-correlation calculations are realized on the GPU, which makes use of parallel computing. We analyzed the effect of the thread number in a block on the GPU streaming multiprocessor utilization efficiency and then compared the acceleration under different calculation scales. By maximizing the streaming multiprocessor utilization efficiency and large calculation scale, a maximum acceleration ratio of 86.01 was obtained.
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http://dx.doi.org/10.1364/AO.412184DOI Listing
December 2020

Are fetal gender and gestational age related to the size of cisterna magna?

J Matern Fetal Neonatal Med 2020 Dec 1:1-8. Epub 2020 Dec 1.

Qilu Hospital of Shandong University, Jinan, China.

Objectives: The purpose of this article was to explore whether the gestational age(GA)and gender could affect the size of the cisterna magna (CM).

Methods: This study that included pregnant women who were between 20 ∼ 39. The recorded included BPD, HC, anteroposterior diameter of CM and gender. The fetuses were divided into normal and isolated enlargement of the CM (IECM)group for statistical analysis.

Results: Seven hundred ninety six fetuses with normal CM, 412 cases were boys and 384 cases were girls. 73 fetuses with IECM, 59 cases were boys and 14 cases were girls. The anteroposterior diameter of the CM increased with GA during 20-26weeks. After 27 weeks, the anteroposterior diameter of CM became stable. In the IECM group, the mean anteroposterior of male and female fetuses were 1.31 ± 0.18 cm and 1.24 ± 0.15 cm, respectively. The IECM fetus accounted for 8.4% of the total number of fetuses, male IECM accounted for 14.3% of normal male fetus, and female fetus was 3.6%, which showed that male fetus had a higher rate of IECM than female (2 = 21.6, <.001).

Conclusions: There is a gender difference between normal fetuses and IECM fetuses. Based on our finding, it is reasonable to establish the normal value of CM according to the gender difference.
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http://dx.doi.org/10.1080/14767058.2020.1849111DOI Listing
December 2020

[Content determination and principal component analysis of nine active components in Paeonia lactiflora flowers from different cultivars and drying methods].

Zhongguo Zhong Yao Za Zhi 2020 Oct;45(19):4643-4651

Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences Beijing 100700, China.

This study aims to establish an UPLC-DAD method for the simultaneous determination of nine active components in phenolic acids, anthocyanins, monoterpene glucosides and flavonoids in the petals of Paeonia lactiflora flowers from different cultivars and processing methods. UPLC analysis was performed on a Waters ACQUITY UPLC HSS T3 C_(18) column(2.1 mm × 100 mm, 1.8 μm)for gradient elution with a mobile phase consisting of 0.5% formic acid solution(A)-acetonitrile(B)at a flow rate of 0.3 mL·min~(-1).The detection wavelength was determined with a switched wavelength method and the column temperature maintained at 20 ℃, with an injection volume of 2 μL.The contents of the above components in the samples with different sources and treatment methods were obtained. The principal component analysis(PCA)of P. lactiflora flowers was conducted by using SIMCA 14.0 software, and the results showed that the P. lactiflora flowers could be classified into two categories according to cultivars, including P. lactiflora 'Bozhou-shaoyao' as one category with high contents of the above components, P. lactiflora 'Baihuachuanshaoyao' and P. lactiflora 'Honghuachuanshaoyao' as the other category. Dried P. lactiflora flowers could be classified into three categories, including baking-drying, sun-drying and shade-drying, with baking-drying method as the optimal one.The P. lactiflora flowers were not greatly affected by origins, growing altitudes, growing years, or blooming stages.The results of contents determination can be used to guide the cultivar selection, harvest and processing of P. lactiflora flowers.
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http://dx.doi.org/10.19540/j.cnki.cjcmm.20200725.301DOI Listing
October 2020

Flow-Induced Crystallization in Polyethylene: Effect of Flow Time on Development of Shish-Kebab.

Polymers (Basel) 2020 Nov 2;12(11). Epub 2020 Nov 2.

Tianjin Key Laboratory of Composite and Functional Materials, School of Materials Science and Engineering, Tianjin University, Tianjin 300350, China.

The flow-induced formation and relaxation of the representative oriented shish-kebab structure were studied with synchrotron small-angle X-ray scattering (SAXS) method. The flow duration was varied from 2 to 6 s at an identical strain rate to reveal the effect of flow time on stability and dimension of formed shish. It was found that the short flow time of 2 s was able to generate shish during flow, which, however, relaxed during the isothermal process after cessation of flow. An increase in flow time can improve the shish stability and the long flow time of 6 s can generate the stable shish that nucleate the growth of kebab lamellae. In addition, the quantitative analysis of SAXS results showed that with increasing flow time from 2 to 6 s, the shish length increased from 242 to 574 nm, while the shish diameter remained around 34 nm. This detailed information of the formed shish-kebab structure can be used to shed light on their evolution that occurred during flow from 2 to 6 s, where shish grew at a longitudinal speed of around 80 nm/s, and there was an improvement in the stability and nucleation capability for kebab lamellae.
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http://dx.doi.org/10.3390/polym12112571DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7693685PMC
November 2020

Optical fiber laser refractometer based on an open microcavity Mach-Zehnder interferometer with an ultra-low detection limit.

Opt Express 2020 Oct;28(21):30570-30585

A fiber laser refractometer based on an open microcavity Mach-Zehnder interferometer (OMZI) is proposed. The open microcavity is constructed by embedding a segment single-mode fiber (SMF) into two multi-mode fiber (MMF) joints with lateral offset for liquid sample, which has the advantages of micro sensing element and easy fabrication. The transmission characteristics of the MMF-assisted OMZI are investigated by simulating and manufacturing the OMZIs with different microcavity lengths and offset distances. By inserting the MMF-assisted OMZI into the erbium-doped fiber ring laser (FRL) cavity, the lasing wavelength can be used to detect the refractive index (RI) change of the medium in the microcavity. Experimental results show a high sensitivity of -2953.444 nm/RIU within the measurement range of 1.33302∼1.33402. More importantly, with the combination of OMZI and FRL, the proposed fiber laser refractometer realizes ultra-low detection limit (DL) and high-quality factor Q, which are two orders of magnitude better than that of previous reports.
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http://dx.doi.org/10.1364/OE.401813DOI Listing
October 2020

Comprehensive role of prostate-specific antigen identified with proteomic analysis in prostate cancer.

J Cell Mol Med 2020 09 27;24(17):10202-10215. Epub 2020 Jul 27.

Department of Urology, The Second Affiliated Hospital of Hainan Medical University, Haikou, China.

Current treatments including androgen deprivation fail to prevent prostate cancer (PrCa) from progressing to castration-resistant PrCa (CRPC). Accumulating evidence highlights the relevance of prostate-specific antigen (PSA) in the development and progression of PrCa. The underlying mechanism whereby PSA functions in PrCa, however, has yet been elucidated. We demonstrated that PSA knockdown attenuated tumorigenesis and metastasis of PrCa C4-2 cells in vitro and in vivo, whereas promoted the apoptosis in vitro. To illuminate the comprehensive role of PSA in PrCa, we performed an isobaric tag for relative and absolute quantitation (iTRAQ)-based proteomic analysis to explore the proteomic change induced by PSA knockdown. Among 121 differentially expressed proteins, 67 proteins were up-regulated, while 54 proteins down-regulated. Bioinformatics analysis was used to explore the mechanism through which PSA exerts influence on PrCa. Protein-protein interaction analysis showed that PSA may mediate POTEF, EPHA3, RAD51C, HPGD and MCM4 to promote the initiation and progression of PrCa. We confirmed that PSA knockdown induced the up-regulation of MCM4 and RAD51C, while it down-regulated POTEF and EPHA3; meanwhile, MCM4 was higher in PrCa para-cancerous tissue than in cancerous tissue, suggesting that PSA may facilitate the tumorigenesis by mediating MCM4. Our findings suggest that PSA plays a comprehensive role in the development and progression of PrCa.
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http://dx.doi.org/10.1111/jcmm.15634DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7520270PMC
September 2020

Oxidation Control of Bottlebrush Molecular Conformation for Producing Libraries of Photonic Structures.

Angew Chem Int Ed Engl 2021 Feb 15;60(7):3647-3653. Epub 2020 Dec 15.

Key Laboratory of Composite and Functional Materials, School of Materials Science and Engineering, Tianjin University, Tianjin, 300350, China.

Self-assembly is important for creating photonic structures and structural color is typically tunable by varying the size of building blocks, which are themselves obtained after time-consuming chemical syntheses. The molecular conformation of bottlebrush block copolymers (BBCPs) in solution can be manipulated to create libraries of photonic structures. Amphiphilic BBCPs bearing oxidation-responsive ferrocene groups on the hydrophilic block are used to fabricate porous particles via evaporation-induced self-assembly of water-in-oil-in-water (W/O/W) double emulsions stabilized by the BBCP surfactant. In situ oxidation of the ferrocene groups by hydrogen peroxide at the W/O interface leads to enhanced hydrophilicity, more hydration, and chain extension of the hydrophilic block. Consequently, larger internal water droplets are spontaneously formed, yielding larger pores within the microparticles. The pore diameter is readily tunable from 144 to 301 nm with a single BBCP, thereby generating full-spectrum structural colors. This work provides a straightforward method for fabrication of libraries of photonic pigments in an easy and scalable manner.
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http://dx.doi.org/10.1002/anie.202011702DOI Listing
February 2021

Anti-tumor activities and mechanisms of Traditional Chinese medicines formulas: A review.

Biomed Pharmacother 2020 Dec 6;132:110820. Epub 2020 Oct 6.

State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China. Electronic address:

Cancer, the leading cause of death in the world nowadays, is a major public health problem. The therapeutic efficacy of cancer is still unsatisfactory despite the development of various treatments. Traditional Chinese medicine (TCM) formulas are a vital therapeutic strategy and new treatment approach for cancer, as they exhibit prospective antitumor potential with multiple targets, multiple signaling pathways and less side effects. In this review, the anticancer functions of a variety of TCM formulas are introduced. The antitumor mechanisms of different TCM formulas are analyzed and summarized. Additionally, the opportunities and challenges of the anti-tumor TCM formulas in the future were also involved. We carried out an extensive review of 173 reports published in PubMed since 1993 to provide support for further research and development of TCM formulas for the therapy of tumor.
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http://dx.doi.org/10.1016/j.biopha.2020.110820DOI Listing
December 2020

P2X Receptor in Primary Afferent Neurons Mediates the Relief of Visceral Hypersensitivity by Electroacupuncture in an Irritable Bowel Syndrome Rat Model.

Gastroenterol Res Pract 2020 16;2020:8186106. Epub 2020 Sep 16.

Shanghai Research Institute of Acupuncture and Meridian, Shanghai University of Traditional Chinese Medicine, Shanghai, China.

Background: Electroacupuncture (EA) has been confirmed effectiveness in the treatment of irritable bowel syndrome (IBS), and P2X receptors in the peripheral and central neurons participate in the acupuncture-mediated relief of the visceral pain in IBS.

Objective: To reveal the neurobiological mechanism that P2X receptor of colonic primary sensory neurons in the dorsal root ganglia of the lumbosacral segment is involved in the alleviation of visceral hypersensitivity by EA in an IBS rat model.

Methods: The IBS chronic visceral pain rat model was established according to the method of Al-Chaer et al. EA at the bilateral He-Mu points, including ST25 and ST37, was conducted for intervention. The behavioral studies, histopathology of colon, electrophysiology, immunofluorescence histochemistry, and real-time polymerase chain reaction assays were used to observe the role of P2X receptor in the colon and related DRG in relieving visceral hypersensitivity by EA.

Results: EA significantly reduced the behavior scores of the IBS rats under different levels (20, 40, 60, 80 mmHg) of colorectal distention stimulation and downregulated the expression levels of P2X receptor protein and mRNA in colon and related DRG of the IBS rats. EA also regulated the electrical properties of the membranes, including the resting membrane potential, rheobase, and action potential of colon-associated DRG neurons in the IBS rats.

Conclusion: EA can regulate the P2X receptor protein and mRNA expression levels in the colon and related DRG of IBS rats with visceral pain and then regulate the excitatory properties of DRG neurons.
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http://dx.doi.org/10.1155/2020/8186106DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7519176PMC
September 2020

Proteomic analysis of bEnd.3 cells infected with wild-type and stk-deficient strains of Streptococcus suis serotype 2 reveals protein and pathway regulation.

J Proteomics 2021 01 19;230:103983. Epub 2020 Sep 19.

College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, China. Electronic address:

Streptococcus suis serotype 2 (SS2) is a zoonotic pathogen causing meningitis in humans and pigs. However, information on the comparative protein expression of the blood-brain barrier (BBB) following SS2 infection is limited. Deletion of the serine/threonine kinase (stk) gene can decrease the ability of SS2 to invade the BBB. In the present study, bEnd.3 cells were used as the BBB model, and a SILAC comparative quantitative proteomic study of bEnd.3 cells infected with the SS2 ZY05719 or Δstk strain was performed to determine the differences between these strains infections. Compared with ZY05719-infected cells, 241 proteins were highly upregulated, and 81 were significantly downregulated in Δstk-infected cells. The obtained data revealed major changes in the proteins involved in RNA process, host cytoskeleton, tight junction disruption and immune response. Some differentially expressed proteins were screened by quantitative real-time PCR to examine their regulation at the transcriptional level, and western blot analysis was used to validate the changes of some selected proteins at the translational level. The results obtained in this study may be useful to understand the host response to SS2 infection and provide crucial clues to decipher how STK expression in SS2 helps the bacteria penetrate the BBB. SIGNIFICANCE: A SILAC comparative quantitative proteomic assay was performed in bEnd.3 cells infected with the SS2 ZY05719 or Δstk strain. 241 upregulated and 81 downregulated differentially expressed proteins (DEPs) were identified. DEPs are involved in RNA process, host cytoskeleton, tight junction disruption and immune response. Some DEPs were examined by qPCR and western blot assays, which were similar to those of their corresponding proteins in the quantitative proteomics analysis.
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http://dx.doi.org/10.1016/j.jprot.2020.103983DOI Listing
January 2021

Virtual-block-array phase analysis for distributed acoustic sensors with a high signal-to-noise ratio reconstruction waveform.

Opt Express 2020 Aug;28(17):24577-24585

A virtual-block-array phase analysis method is proposed for the fiber-optic distributed acoustic sensor. The sensing fiber is divided into a serial of discrete virtual blocks according to the pulse spatial length. The phase variation caused by acoustic events is obtained by combining the operation of the temporal differential process between traces and local spatial average in virtual blocks. The linear frequency-modulated probe pulse produces phase compensation effects at the event location. High signal-to-noise ratio (SNR) measurement is verified by simulation and experiment. The reconstructed waveform of 1.5 kHz sinusoidal signal showed a root mean square error of 0.0359 and an SNR of 47.28 dB.
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http://dx.doi.org/10.1364/OE.395281DOI Listing
August 2020

Dual drug-loaded nano-platform for targeted cancer therapy: toward clinical therapeutic efficacy of multifunctionality.

J Nanobiotechnology 2020 Sep 4;18(1):123. Epub 2020 Sep 4.

State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China.

Background: Poor targeting and penetration of chemotherapy drugs in solid tumors, and the development of resistance to chemotherapeutic agents are currently hindering the therapy of breast cancer; meanwhile, breast cancer metastasis is one of the leading causes of death in breast cancer patients. With the development of nanotechnology, nanomaterials have been widely used in tumor therapy.

Results: A multi-functional nano-platform containing gambogic acid (GA) and paclitaxel (PTX) was characterized by a small size, high encapsulation efficiency, slow release, long systemic circulation time in vivo, showed good targeting and penetrability to tumor tissues and tumor cells, and exhibited higher anti-tumor effect and lower systemic toxicity in BALB/c mice bearing 4T1 tumor. GA not only overcame the multidrug resistance of PTX by inhibiting P-glycoprotein (P-gp) activity in MCF-7/ADR cells, but also inhibited MDA-MB-231 cells migration and invasion, playing a crucial role in preventing and treating the lung metastasis of breast cancer caused by PTX; meanwhile, the synergistic anti-tumor effect of GA and PTX has also been verified in vitro and in vivo experiments.

Conclusion: Our data described the better recognition and penetration of tumor cells of R9dGR-modified versatile nanosystems containing GA and PTX, which exerted one stone three birds clinical therapeutic efficacy of multifunctionality.
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http://dx.doi.org/10.1186/s12951-020-00681-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7650261PMC
September 2020

Streptavidin Promotes DNA Binding and Activation of cGAS to Enhance Innate Immunity.

iScience 2020 Aug 14;23(9):101463. Epub 2020 Aug 14.

Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Department of Biochemistry and Biophysics, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. Electronic address:

cGAS/STING signaling plays an essential role in sensing cytosolic DNA. cGAS activity is regulated by posttranslational modifications and binding partners. cGAS interactome largely includes mammalian or viral proteins. Whether and how bacterial proteins bind cGAS to modulate innate immunity remain elusive. Here, we found streptavidin, a secreted bacterial protein, selectively bound cGAS to promote DNA-induced cGAS activation and interferon-β production. Mechanistically, streptavidin enhanced DNA binding and cGAS phase separation, therefore facilitating cGAS activation. Using an HSV-1-infected mouse model, we found streptavidin nanoparticles facilitated HSV-1 clearance through improving innate immunity. Considering the clinical usage of streptavidin as an immune stimulant and drug delivery vehicle and its biotechnological usage for biotin-labeled protein purification and detection, our studies not only provide an example for a bacterial protein regulating cGAS activity but also suggest caution needs to be taken when using streptavidin in various applications given to its ability to induce innate immunity.
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http://dx.doi.org/10.1016/j.isci.2020.101463DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7476851PMC
August 2020

A case of a vaginal Brenner tumor without a gland mimicking a borderline tumor: unusual morphology and diagnostic pitfalls.

J Int Med Res 2020 Aug;48(8):300060520946536

Department of Pathology, Tianjin Third Central Hospital, Tianjin, China.

Brenner tumor is a rare neoplasm of the vagina. This tumor is diagnosed according to the criteria of ovarian tumors. We report here a 64-year-old postmenopausal woman with a 2.0-cm sessile vaginal polyp for 9 years. Microscopic examination showed unusual features of no gland appearing in the tumor, but the other two characteristic components of transitional islands and dense fibrous stroma were observed. The tumor was diagnosed as a vaginal Brenner tumor on the basis of the definition proposed by the World Health Organization classification of female reproductive organ tumors. In our case, part of the epithelial nests of the Brenner tumor showed basaloid cell differentiation with peripheral palisading, and irregular papillary hyperplasia was observed around the epithelial nests similar to a borderline tumor. However, no mitotic activity or nuclear atypia was present in either the epithelial or stromal components. The presence of epithelial nests requires attention in the medical history of the patient. Our patient did not have a history of primary urothelial carcinoma. Our patient's benign vaginal Brenner tumor with different morphological characteristics supports the current notion that Walthard nests might act as possible precursor lesions.
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http://dx.doi.org/10.1177/0300060520946536DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7436852PMC
August 2020

PagC is involved in salmonella pullorum OMVs production and affects biofilm production.

Vet Microbiol 2020 Aug 23;247:108778. Epub 2020 Jun 23.

MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, 210095, China; Ministry of Agriculture Key Laboratory of Animal Bacteriology, Nanjing, 210095, China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, 225009, China. Electronic address:

The pagC gene is ubiquitously distributed in Salmonella, but there is limited information regarding its function. Pullorum disease (PD) is a septicemic disease caused by Salmonella Pullorum, which also harbors the pagC gene. In this study, we constructed an S. Pullorum pagC gene deletion strain and its complemented strain. First, we confirmed that the pagC gene does not participate in bacterial growth regulation or environmental pH adaptation. Interestingly, the results of subsequent analyses indicated that the pagC gene defect led to increased bacterial colonization in the intestine (especially in the cecum) and increased biofilm formation, while the number of outer-membrane vesicles (OMVs) in the bacterial culture decreased. Purified OMVs were able to reduce S. Pullorum biofilm formation in vitro. In addition, the results of a mass spectrometry analysis of purified OMVs indicated that some enzymes harbored by OMVs may be involved in biofilm degradation. Based on these results, we conclude that deletion of the pagC gene leads to reduced S. Pullorum OMVs production, which subsequently promotes biofilm stability, increases bacterial colonization in the intestine, and potentially inhibits the switch from sessile to planktonic growth.
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http://dx.doi.org/10.1016/j.vetmic.2020.108778DOI Listing
August 2020

PPP6C Negatively Regulates STING-Dependent Innate Immune Responses.

mBio 2020 08 4;11(4). Epub 2020 Aug 4.

Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA

Stimulator of interferon genes (STING) is an essential adaptor protein of the innate DNA-sensing signaling pathway, which recognizes genomic DNA from invading pathogens to establish antiviral responses in host cells. STING activity is tightly regulated by several posttranslational modifications, including phosphorylation. However, specifically how the phosphorylation status of STING is modulated by kinases and phosphatases remains to be fully elucidated. In this study, we identified protein phosphatase 6 catalytic subunit (PPP6C) as a binding partner of Kaposi's sarcoma-associated herpesvirus (KSHV) open reading frame 48 (ORF48), which is a negative regulator of the cyclic GMP-AMP synthase (cGAS)-STING pathway. PPP6C depletion enhances double-stranded DNA (dsDNA)-induced and 5'ppp double-stranded RNA (dsRNA)-induced but not poly(I:C)-induced innate immune responses. PPP6C negatively regulates dsDNA-induced IRF3 activation but not NF-κB activation. Deficiency of PPP6C greatly inhibits the replication of herpes simplex virus 1 (HSV-1) and vesicular stomatitis virus (VSV) as well as the reactivation of KSHV, due to increased type I interferon production. We further demonstrated that PPP6C interacts with STING and that loss of PPP6C enhances STING phosphorylation. These data demonstrate the important role of PPP6C in regulating STING phosphorylation and activation, which provides an additional mechanism by which the host responds to viral infection. Cytosolic DNA, which usually comes from invading microbes, is a dangerous signal to the host. The cGAS-STING pathway is the major player that detects cytosolic DNA and then evokes the innate immune response. As an adaptor protein, STING plays a central role in controlling activation of the cGAS-STING pathway. Although transient activation of STING is essential to trigger the host defense during pathogen invasion, chronic STING activation has been shown to be associated with several autoinflammatory diseases. Here, we report that PPP6C negatively regulates the cGAS-STING pathway by removing STING phosphorylation, which is required for its activation. Dephosphorylation of STING by PPP6C helps prevent the sustained production of STING-dependent cytokines, which would otherwise lead to severe autoimmune disorders. This work provides additional mechanisms on the regulation of STING activity and might facilitate the development of novel therapeutics designed to prevent a variety of autoinflammatory disorders.
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http://dx.doi.org/10.1128/mBio.01728-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7407089PMC
August 2020

Sleeve gastrectomy ameliorates alveolar structures and surfactant protein expression in lungs of obese and diabetic rats.

Int J Obes (Lond) 2020 12 27;44(12):2394-2404. Epub 2020 Jul 27.

Department of General Surgery, The First Affiliated Hospital of Shandong First Medical University, Jinan, Shandong Province, 250014, People's Republic of China.

Background: Bariatric surgeries have been shown to be effective in reversing damaged pulmonary function in individuals suffering from obesity and type 2 diabetes mellitus, whereas its underlying mechanisms remain largely unknown.

Methods: Sleeve gastrectomy (SG) was performed on obese and diabetic Wistar rats, and their pulmonary function and lung tissues were compared to sham-operated (SH) obese and diabetic rats, and age-matched healthy controls (C) to explore the improvements in microstructures and expression of surfactant protein (SP)-A and -C at postoperative 4th, 8th, and 12th week.

Result: Apart from the profound metabolic changes and improvement in pulmonary function, lung volume was restored along with an improved diffusion capacity noted by thinned capillary basement membrane and decreased harmonic mean length of diffusion barrier in SG rats. The digital slices of light microscope showed the general changes brought on by the SG, including normalized basic structures, ameliorated inflammatory status, as well as reduced lipid deposition, where the hydroxyproline (HYP), triglyceride (TG) assays, and electron microscope further suggested that the improvement in alveolar structures lies in reduced collagen fibers, lipids and septal tissues, increased capillary blood, and normalized alveolar type 2 (AT2) cells. Besides, disrupted SP-A and SP-C expression were also normalized after SG.

Conclusion: The improvement of lung function after SG is related to the ameliorated alveolar structures, and surface protein expression induced by weight loss and improved glucose metabolism.
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http://dx.doi.org/10.1038/s41366-020-0647-yDOI Listing
December 2020

LINC00319 Promotes Cervical Cancer Progression Via Targeting miR-147a/IGF1R Pathway.

Cancer Biother Radiopharm 2020 Jul 9. Epub 2020 Jul 9.

Department of Gynecology, The First Affiliated Hospital of Chengdu Medical College, Chengdu City, China.

Cervical cancer is identified as the fourth most common female malignancy worldwide. Recently, Linc00319 was reported to play an important role in the development and progression of cervical cancer. However, little is known about the molecular mechanism and clinical significance of Linc00319 in the carcinogenesis of cervical cancer. This study aims to reveal the biological function and molecular mechanisms of Linc00319 in cell proliferation, invasion, and migration of cervical cancer. In the current study, gene expression levels of Linc00319, miR-147a, and IFG1R were detected by quantitative real-time PCR in clinical tissue samples and cervical cancer cell lines. Protein levels were also determined by western blot assay in cervical cancer cells. CCK-8, transwell, and wound healing assays were used to test the proliferation, invasion, and migration of cervical cancer cell lines . Target genes were predicted through bioinformatics methods and then verified by gene engineering technology. The authors' results showed that Linc00319 was upregulated in cervical cancer tissues and cell lines, while Linc00319silencing could inhibit cervical cancer cell proliferation, invasion, and migration. Further investigations showed that Linc00319 interacted with miR-147a and inhibited its expression, unregulated IGF1R to induce progression of cervical cancer. Their research indicated that Linc00319 might play an oncogenic role in cervical cancer and regulate the progression of cervical tumor growth by inhibiting the expression of miR-147a and activating IGF1R-related pathway. The findings suggest a novel molecular biomarker and therapeutic target for cervical tumor and may provide a novel therapeutic strategy for preventing the metastasis of cervical cancer.
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http://dx.doi.org/10.1089/cbr.2020.3722DOI Listing
July 2020

Electroacupuncture Improves IBS Visceral Hypersensitivity by Inhibiting the Activation of Astrocytes in the Medial Thalamus and Anterior Cingulate Cortex.

Evid Based Complement Alternat Med 2020 12;2020:2562979. Epub 2020 Jun 12.

Key Laboratory of Acupuncture and Immunological Effects, Shanghai University of Traditional Chinese Medicine, Shanghai 200030, China.

Objective: To explore whether the effect of electroacupuncture (EA) on visceral hypersensitivity (VH) in rats with irritable bowel syndrome (IBS) is related to the changes of astrocyte activation in the medial thalamus (MT) and anterior cingulate cortex (ACC).

Method: Male Sprague-Dawley rats were randomly divided into the normal control (NC) group, model control (MC) group, electroacupuncture (EA) group, and fluorocitrate (FCA) group. A model of visceral hypersensitivity was established by neonatal colorectal irritation. In the EA group, needles were inserted into the skin at the Tianshu (ST25) and Shangjuxu (ST37) acupoints, once a day for 7 days. The FCA group received intrathecal injection of FCA on the 1st, 4th, and 7th days. Visceral hypersensitivity was evaluated by the abdominal withdrawal reflex (AWR), and glial fibrillary acidic protein (GFAP) mRNA and protein levels in the MT and ACC were detected by real-time PCR, immunohistochemistry, and western blots.

Results: The AWR score in the MC group was significantly higher than in the NC group, and EA and FCA reduced the AWR score of VH rats. GFAP mRNA and protein levels in the MT and ACC of rats in the MC group were significantly increased compared with the NC group. After either electroacupuncture or fluorocitrate, GFAP mRNA and protein levels in the MT and ACC were both clearly reduced.

Conclusion: Electroacupuncture alleviates IBS visceral hypersensitivity by inhibiting the activation of astrocytes in the MT and ACC.
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http://dx.doi.org/10.1155/2020/2562979DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7306073PMC
June 2020

Primary hepatic neuroendocrine carcinoma coexisting with distal cholangiocarcinoma: A case report and review of the literature.

Medicine (Baltimore) 2020 Jun;99(26):e20854

Department of Pathology, Third Central Hospital of Tianjin, Tianjin Third Central Hospital affiliated to Nankai University, Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases.

Introduction: Although primary hepatic neuroendocrine carcinomas, whose prognostic mechanisms remain unclear, are rare, coexistence of neuroendocrine carcinomas and other tumors is rarer. In this report, we describe a unique case of coexistence between primary hepatic neuroendocrine carcinoma and a distal cholangiocarcinoma in the pancreas.

Patient Concerns: A 64-year-old woman with a history of diabetes, but none of hepatitis, was admitted to hospital because of intermittent epigastric distension and pain discomfort for more than 1 month aggravated 1 day. A contrast-enhanced computed tomography (CT) scan of the upper abdomen and abdominal magnetic resonance imaging (MRI) revealed a thickening of the bile duct wall in the middle and lower segment of common bile duct and the corresponding lumen is narrow and low-density tumors with ring enhancement (1.83 cm × 1.9 cm) in lobi hepatis dexte.

Diagnosis: Primary neuroendocrine carcinoma of the liver was diagnosed to be coexisting with a distal cholangiocarcinoma, which had invaded the pancreas. Immunohistochemical examination revealed that the neoplastic cells strongly expressed chromogranin A, synaptophysin, and CD56 proteins. The tumor cells did not express HepPar-1, glypican-3, S-100, CK7, and CK19 in the liver tumor. A distal bile duct in pancreatic tissues shows the characteristics of typical bile duct carcinoma, as an invasion of carcinoma is also seen in the pancreatic tissues. Gastrointestinal endoscopy, chest and abdominal CT, abdominal MRI, and positron emission tomography (PET)-CT were used to exclude metastatic neuroendocrine tumors of the liver.

Interventions: Resection of the pancreas-duodenum, the right anterior lobe of the liver, and regional lymph nodes was performed in patients.

Outcomes: The patient had survived for 5 months after the operation.

Conclusion: A unique case of a coexistence of primary hepatic neuroendocrine carcinoma and a distal cholangiocarcinoma, which had invaded the pancreas. No treatment guidelines are established for the treatment of the unique case.
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http://dx.doi.org/10.1097/MD.0000000000020854DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7328923PMC
June 2020