Publications by authors named "Huan Xia"

88 Publications

Denudatine-type diterpenoid alkaloids from an aqueous extract of the lateral root of .

J Asian Nat Prod Res 2021 Jun 3:1-12. Epub 2021 Jun 3.

State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.

Five new denudatine-type diterpenoid alkaloids (1-5), along with the known analogue aconicarmine (), were isolated from an aqueous decoction of the lateral roots of (fu-zi). Their structures were determined by spectroscopic data analysis and electronic circular dichroism (ECD) calculations. Compound is the first denudatine-type diterpenoid alcohol iminium alkaloid, which could be partially transformed into the aza acetal form in pyridine-. Compound inhibited mice writhing in an acetic acid-induced writhing assay.
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http://dx.doi.org/10.1080/10286020.2021.1931141DOI Listing
June 2021

Sertoli cell-derived exosome-mediated transfer of miR-145-5p inhibits Leydig cell steroidogenesis by targeting steroidogenic factor 1.

FASEB J 2021 Jun;35(6):e21660

Department of Cell Biology & Guangdong Provincial Key Laboratory of Bioengineering Medicine, Jinan University, Guangzhou, China.

In the mammalian testis, two distinct populations of Sertoli cells (SCs), the immature SCs (ISCs) and adult SCs (ASCs), play significant roles in regulating the development and function of Leydig cells. However, the effect of different SC types on the function of Leydig cells is poorly understood. Here, our study showed that miR-145-5p expression was significantly different in SCs at different stages, with the highest expression observed in ISCs. Exosomes mediate the transfer of miR-145-5p from ISCs to Leydig cells. Overexpression of miR-145-5p in Leydig cells significantly downregulated steroidogenic gene expression and inhibited testosterone synthesis. Additionally, miR-145-5p functioned by directly targeted steroidogenic factor-1 (Sf-1) and downregulated the expression of SF-1, which further downregulated the expression of steroidogenic genes, induced accumulation of lipid droplets, and eventually suppressed testosterone production. These findings demonstrate that SC-derived miR-145-5p plays a significant role in regulating the functions of Leydig cells and may therefore serve as a diagnostic biomarker for male hypogonadism developmental abnormalities during puberty.
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http://dx.doi.org/10.1096/fj.202002589RRRRDOI Listing
June 2021

Enzymatic Cascade Reactions Mediated by Highly Efficient Biomimetic Quasi Metal-Organic Frameworks.

ACS Appl Mater Interfaces 2021 May 9;13(19):22240-22253. Epub 2021 May 9.

Guangdong Provincial Key Lab of Green Chemical Product Technology, School of Chemistry and Chemical Engineering, South China University of Technology, Guangzhou 510640, China.

The integration of chemo- and enzymatic catalysis for effective multistep cascades has presented critical challenges for decades. In this work, the biomimetic quasi NH-MIL-101 (qNM) with highly efficient peroxidase-like activity was synthesized via a palmitic acid-induced strategy followed by pyrolysis. The effects of the amount of palmitic acid and calcination temperature on the synthesis of qNM were optimized. It was found that qNM was an excellent catalyst for oxidations of various peroxidase substrates, and a possible mechanism was proposed, i.e., the presence of Fe species in qNM was responsible for its excellent activity, which facilitated the transition between Fe and Fe species to produce more hydroxyl radicals by HO decomposition. The qNM served as the potential matrix for enzyme immobilization through a cross-linking method, and kinetic studies revealed that the catalytic efficiency (/) for the immobilized GOx (23.7 mM s) is comparable to that of free GOx (26.9 mM s). The immobilized GOx also showed improved stability against high temperatures and organic solvents compared to free GOx, and analysis of the secondary structure of GOx indicated that the improved stability resulted from enzyme rigidity by the intense covalent linkage with qNM. Furthermore, qNM contributed its biomimetic activity to cooperate with a single enzyme (GOx) or two enzymes (β-Gal and GOx) for the enzymatic cascade reactions. Compared with the mixture of each component in the solution, the combination of the single-enzyme system (GOx) or the two-enzyme system (β-Gal and GOx) in qNM achieved 2.67-fold and 1.83-fold enhancements in the activity of catalytic cascades, respectively. This study provides new insights into the construction of effective and synergistic cascade reactions by integrating biomimetic MOF with natural enzyme, which holds potential for applications in biotechnology and ecofriendly and biomimetic catalysis.
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http://dx.doi.org/10.1021/acsami.1c04680DOI Listing
May 2021

The basic route of nuclear-targeted transport of IGF-1/IGF-1R and potential biological functions in intestinal epithelial cells.

Cell Prolif 2021 Jun 1;54(6):e13030. Epub 2021 May 1.

Department of Intensive care unit, The first hospital of Jilin University, Changchun, China.

Objectives: Insulin-like growth factor (IGF-1) plays an important role in many biological processes in the intestinal tract. However, the cellular behaviour and characteristics of IGF-1/IGF-1R in intestinal cells remain unclear.

Materials And Methods: A series of techniques (such as indirect immunofluorescence, co-localization and Western blot) have been used to systematically study the cellular behaviour of IGF-1/IGF-1R on intestinal cells.

Results: We found that IGF-1 can not only internalize into the cytoplasm, but also transport into the cell nuclei. We systematically studied the detailed molecular pathways of IGF-1/IGF-1R's nuclear translocation. We found that IGF-1R underwent clathrin-mediated endocytosis into cells and then entered into Rab-5-positive endosomes. Dynein/dynactin were used as motors to drive Rab-5-positive endosomes carrying IGF-1R (cargo molecule) to Golgi apparatus (transit station) along the surface of the microtubule. IGF-1 and/or IGF-1R entered the cell nuclei through NPC (nuclear pore complex), a process mediated by NUP358. Further study indicated that nuclear localization of IGF-1 and/or IGF-1R promoted cell proliferation and increased the nuclear residence time of signalling molecules activated by IGF-1. Further experiments showed that IGF-1R may regulate the transcription of genes in the cell nuclei, indicating that nuclear-localized IGF-1R plays an important in cell proliferation.

Conclusions: In short, we revealed the molecular mechanism by which IGF-1/IGF-1R transports into the cell nuclei of intestinal cells. More importantly, the current work showed that the nuclear-localized IGF-1R has important biological functions.
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http://dx.doi.org/10.1111/cpr.13030DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8168413PMC
June 2021

Analysis of the Characteristics of TIGIT-Expressing CD3CD56NK Cells in Controlling Different Stages of HIV-1 Infection.

Front Immunol 2021 26;12:602492. Epub 2021 Feb 26.

Department of Infectious Diseases and Medical Immunology, Beijing Youan Hospital, Capital Medical University, Beijing, China.

TIGIT expression on natural killer (NK) cells is associated with dysfunction during chronic HIV infection, but the phenotype and biological functions of these cells in the context of acute HIV-1 infection remain poorly understood. Here, 19 acutely infected HIV-1 patients traced at first, third and twelfth month, and age-matched patients with chronic HIV-1 infection were enrolled to investigate the phenotype and functions of TIGIT expression on NK cells. We found that TIGIT-expressing NK cells did not increase in frequency in the first, third and twelfth month of infection until chronic HIV-1 infection lasted over 2 years. The number of TIGITNK cells in acute infection was positively associated with HIV-1 viral load ( = 0.53, = 0.0009). CD96 was significantly upregulated on NK cells after acute infection for 1 month and in chronic infection over 2 years, while CD226 was downregulated in chronic infection over 2 years. Further, at different stages of infection, CD96CD226 cells diminished among total NK cells, TIGITNK and TIGITNK cells, while CD96CD226 cells expanded. Reduced CD96CD226 cells and elevated CD96CD226 cells among NK cells especially TIGITNK cells, had opposite associations with viral load in the first month of infection, as well as CD4 T-cell counts in including the twelfth month and more than 2 years of chronic infection. In both HIV-1-infected individuals and healthy donors, TIGIT was predominantly expressed in NKG2ANKG2CNK cells, with a significantly higher proportion than in NKG2ANKG2CNK cells. Moreover, the frequencies of TIGITNK cells were positively associated with the frequencies of NKG2ANKG2CNK cells in acute infection ( = 0.62, < 0.0001), chronic infection ( = 0.37, = 0.023) and healthy donors ( = 0.36, = 0.020). Enhanced early activation and coexpression of CD38 and HLA-DR in TIGITNK cells were detected compared to TIGITNK cells, both of which were inversely associated with the decrease in CD4 T-cell counts in both acute and chronic HIV-1 infection. The ability of TIGITNK cells to produce TNF-α, IFN-γ and CD107a degranulation substance were consistently weaker than that of TIGITNK cells in both acute and chronic infection. Moreover, the functionalities of TIGITNK cells were lower than those of TIGITNK cells, except for TNF-αCD107aIFN-γNK cells. These findings highlight the phenotype and functional characteristics of TIGIT-expressing NK cells which have poor capabilities in inhibiting HIV-1 replication and maintaining CD4 T-cell counts.
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http://dx.doi.org/10.3389/fimmu.2021.602492DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7953050PMC
February 2021

Paeonone A, a novel nonanortriterpenoid from the roots of Paeonia lactiflora.

Bioorg Chem 2021 May 2;110:104783. Epub 2021 Mar 2.

State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China; Key Laboratory of Chinese Internal Medicine of Ministry of Education and Beijing, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing 100700, China. Electronic address:

Paeonone A (1), a unique nonanortriterpenoid, and a new octanortriterpenoid, paeonone B (2), were isolated from the roots of Paeonia lactiflora, together with a known analogue, palbinone (3). Paeonone A (1) is the first example of naturally occurring nonanortriterpenoid with a diketo acid group. Extensive NMR and HRESIMS experiments were applied to identify the structures of 1 and 2, and their absolute configurations were solved by single-crystal X-ray diffraction and ECD data. Biological properties of 1-3 were explored against pancreatic lipase and cancer cell lines.
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http://dx.doi.org/10.1016/j.bioorg.2021.104783DOI Listing
May 2021

Effect of Selenium and Peroxynitrite on Immune Function of Immature Dendritic Cells in Humans.

Med Sci Monit 2021 Mar 8;27:e929004. Epub 2021 Mar 8.

Immune Cells and Antibody Engineering Research Center of Guizhou Province/Key Laboratory of Biology and Medical Engineering, Guizhou Medical University, Guiyang, Guizhou, China (mainland).

BACKGROUND Selenium and peroxynitrite are known to support the growth and activity of immune cells, including T cells, B cells and macrophages. However, the role of these factors in the immune function of human immature dendritic cells (imDCs) is not clear. MATERIAL AND METHODS Monocytes from a mixture of blood samples were isolated using Ficoll density gradient centrifugation and purified with immunomagnetic beads before being induced into imDCs. Cells then either received no treatment (control group), or treatment with sodium selenite (Na₂SeO₃, Se), 3-morpholinosydnonimine (SIN1, which decomposes into peroxynitrite), or Se+SIN1. Cell viability, migration, and antiphagocytic abilities, oxidative stress, and protein expression of extracellular signal-regulated kinases (ERK) and MMP2 were assessed using a CCK8 assay, cell counter and flow cytometry, microplate spectrophotometer, and Western blot analysis, respectively. RESULTS Viability of imDCs was unaffected by 0.1 μmol/L of Na₂SeO₃, although 1 mmol/L of SIN1 decreased it significantly (P<0.05). Chemotactic migration and antiphagocytic abilities were inhibited and enhanced, respectively, by treatment with Na₂SeO₃ and SIN1 (P<0.05). Activities of superoxide dismutase and glutathione peroxidase were increased by Na2SeO3 and Se+SIN1 (P<0.001). Glutathione content decreased with exposure to Na₂SeO₃ and SIN1 (P<0.05), but increased after treatment with Se+SIN1 (P<0.05). Levels of reactive oxygen species only increased with SIN1 treatment (P<0.05). Treatment with Na₂SeO₃, SIN1 and Se+SIN1 increased ERK phosphorylation and decreased MMP2 protein expression (P<0.05). CONCLUSIONS Selenium and peroxynitrite can influence immune function in imDCs by regulating levels of reactive oxygen species or glutathione to activate ERK and promote antigen phagocytosis, as well as by decreasing MMP2 expression to inhibit chemotactic migration.
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http://dx.doi.org/10.12659/MSM.929004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7953518PMC
March 2021

Sertoli cell-derived exosomal MicroRNA-486-5p regulates differentiation of spermatogonial stem cell through PTEN in mice.

J Cell Mol Med 2021 Apr 19;25(8):3950-3962. Epub 2021 Feb 19.

Department of Cell Biology & Guangdong Provincial Key Laboratory of Bioengineering Medicine, Jinan University, Guangzhou, China.

Self-renewal and differentiation of spermatogonial stem cell (SSC) are critical for male fertility and reproduction, both of which are highly regulated by testicular microenvironment. Exosomal miRNAs have emerged as new components in intercellular communication. However, their roles in the differentiation of SSC remain unclear. Here, we observed miR-486-5p enriched in Sertoli cell and Sertoli cell-derived exosomes. The exosomes mediate the transfer of miR-486-5p from Sertoli cells to SSCs. Exosomes release miR-486-5p, thus up-regulate expression of Stra8 (stimulated by retinoic acid 8) and promote differentiation of SSC. And PTEN was identified as a target of miR-486-5p. Overexpression of miR-486-5p in SSCs down-regulates PTEN expression, which up-regulates the expression of STRA8 and SYCP3, promotes SSCs differentiation. In addition, blocking the exosome-mediated transfer of miR-486-5p inhibits differentiation of SSC. Our findings demonstrate that miR-486-5p acts as a communication molecule between Sertoli cells and SSCs in modulating differentiation of SSCs. This provides a new insight on molecular mechanisms that regulates SSC differentiation and a basis for the diagnosis, treatment, and prevention of male infertility.
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http://dx.doi.org/10.1111/jcmm.16347DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8051706PMC
April 2021

Thermo-responsive polymer encapsulated gold nanorods for single continuous wave laser-induced photodynamic/photothermal tumour therapy.

J Nanobiotechnology 2021 Feb 8;19(1):41. Epub 2021 Feb 8.

Department of Respiratory Disease, The First Affiliated Hospital of Bengbu Medical College, Bengbu, 233004, China.

Owing to strong and tunable surface plasmon resonance (SPR) effect and good biocompatibility, gold nanoparticles have been suggested to be a versatile platform for a broad range of biomedical applications. In this study, a new nanoplatform of thermo-responsive polymer encapsulated gold nanorods incorporating indocyanine green (ICG) was designed to couple the photothermal properties of gold nanorods (AuNRs) and the photodynamic properties of ICG to enhance the photodynamic/photothermal combination therapy (PDT/PTT). In addition to the significantly increased payload and enhancing photostability of ICG, the polymer shell in the nanoplatform also has thermo-responsive characteristics that can control the release of drugs at tumour sites upon the laser irradiation. On the basis of these improvements, the nanoplatform strongly increased drug aggregation at the tumour site and improved the photothermal/photodynamic therapeutic efficacy. These results suggest that this nanoplatform would be a great potential system for tumour imaging and antitumour therapy.
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http://dx.doi.org/10.1186/s12951-020-00754-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7869504PMC
February 2021

[Chemical constituents from ethyl acetate soluble extraction of Litsea cubeba].

Zhongguo Zhong Yao Za Zhi 2020 Dec;45(24):5877-5883

Key Laboratory of Chinese Internal Medicine of Ministry of Education and Beijing, Dongzhimen Hospital, Beijing University of Chinese Medicine Beijing 100700, China State Key Laboratory of Bioactive Substance and Function of Natural Medicines,Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College Beijing 100050, China.

Chemical investigation on the constituents of the ethyl acetate soluble extraction of Litsea cubeba has resulted in the isolation and structure elucidation of thirty compounds, including one sesquiterpene(1), four monoterpenes(2-5), two γ-butyrolactone derivatives(6 and 7), seven tyramine derivatives(8-14), fifteen aromatic compounds(15-29), and one pyrone derivative(30) via various chromatographic techniques and spectroscopic data analysis(MS, IR, 1 D and 2 D NMR). Compounds 1-7, 13 and 14 were obtained from the genus Litsea for the first time.
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http://dx.doi.org/10.19540/j.cnki.cjcmm.20200820.202DOI Listing
December 2020

[Research progress on animal models of chronic pain and its application in traditional Chinese medicine research].

Zhongguo Zhong Yao Za Zhi 2020 Dec;45(24):5866-5876

Key Laboratory of Chinese Internal Medicine of Ministry of Education and Beijing, Dongzhimen Hospital,Beijing University of Chinese Medicine Beijing 100700, China.

The classification of chronic pain is complex and its pathogenesis is not clear, which led to the limited progress of treatment measures.Traditional Chinese medicine(TCM) has certain advantages in the treatment of chronic pain, and its mechanism needs further exploration. The ideal animal model is helpful to elucidate the key mechanism of the occurrence and development of chronic pain and play an important role in the discovery of new drug targets, the development of new therapies and the research on the analgesic mechanism of TCM.In recent years, many scholars at home and abroad have done a lot of research to explore the pathogenesis of chronic pain and the mechanism of TCM, which have achieved some results. On this basis, this study summarizes the selection of experimental animals for chronic pain and the commonly evaluation methods of animal models. According to the latest international classification of diseases, this review organizes the induced methods, evaluation indicators, advantages and disadvantages of seven kinds of chronic pain animal models, such as chronic primary pain, chronic cancer-related pain and so on. Next, this review introduces the chronic pain animal models commonly used in TCM research, in order to provide guidance for the targeted selection of animal models when carrying out relevant experiments in the future.
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http://dx.doi.org/10.19540/j.cnki.cjcmm.20200924.201DOI Listing
December 2020

[Research progress of natural non-alkaloids with analgesic activity].

Zhongguo Zhong Yao Za Zhi 2020 Dec;45(24):5840-5865

Key Laboratory of Chinese Internal Medicine of Ministry of Education and Beijing,Dongzhimen Hospital,Beijing University of Chinese Medicine Beijing 100700,China State Key Laboratory of Bioactive Substance and Function of Natural Medicines,Institute of Materia Medica,Chinese Academy of Medical Sciences and Peking Union Medical College Beijing 100050,China.

Pain is a complex, unpleasant feeling and emotional experience associated with actual or potential tissue damage, and manifests itself in certain autonomous psychological and behavioral responses. The commonly used opioid and non-steroidal anti-inflammatory analgesics(NSAIDs) may cause adverse reactions to the kidney, liver, cardiovascular or gastrointestinal system and cause problems of drug abuse. Therefore, it is necessary to study new analgesic drugs with less side effects and significant analgesic effects. A variety of natural products derived from terrestrial plants, microorganisms, marine organisms and fungi have been an important source of clinical medicines and provide an inexhaustible resource for the development and innovation of modern medicines. Therefore, this paper mainly reviews the natural non-alkaloids with analgesic activity in order to provide reference for the research and development of analgesic drugs derived from natural products.
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http://dx.doi.org/10.19540/j.cnki.cjcmm.20201104.201DOI Listing
December 2020

[Research progress of natural alkaloids with analgesic activity].

Zhongguo Zhong Yao Za Zhi 2020 Dec;45(24):5829-5839

Key Laboratory of Chinese Internal Medicine of Ministry of Education and Beijing,Dongzhimen Hospital,Beijing University of Chinese Medicine Beijing 100700,China State Key Laboratory of Bioactive Substance and Function of Natural Medicines,Institute of Materia Medica,Chinese Academy of Medical Sciences and Peking Union Medical College Beijing 100050,China.

Pain is a protective defense response of the body to harmful stimuli. Long-term pain not only seriously affects the body of the patient and brings great pain to the patient, but also brings huge economic burden to the patient's family and society. It has become one of the most serious problems affecting human health. At present, opioids and non-steroidal anti-inflammatory drugs(NSAIDs) are commonly used as painkillers, but they tend to cause a variety of adverse reactions or risk of addiction. To find and develop new analgesic drugs, which are safer and more effective, has become the hot spot and difficulty in medical research. A variety of alkaloids derived from terrestrial plants, microorganisms, marine organisms and fungi have been an important source of clinical analgesic medicines. Various alkaloids have been proved to have good analgesic effects, such as morphine and the related to opioids, the main analgesic active components from Corydalis Rhizoma and Aconiti Lateralis Radix Praeparata. Here we summarized the research progress of natural alkaloids with analgesic activity, in order to provide reference for the research and development of analgesic drugs based on natural products.
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http://dx.doi.org/10.19540/j.cnki.cjcmm.20200909.201DOI Listing
December 2020

Safety and efficacy of allogeneic natural killer cell immunotherapy on human immunodeficiency virus type 1 immunological non-responders: a brief report.

Chin Med J (Engl) 2020 Dec;133(23):2803-2807

Department of Infectious Diseases, Nankai University Second People's Hospital, Tianjin 300192, China.

Background: Allogeneic natural killer (NK) cell immunotherapy is recognized as a promising anti-tumor strategy, but whether it plays a role in poor CD4 recovery among human immunodeficiency virus type 1 (HIV-1) infected patients is unknown. This study aimed to investigate the safety and effectiveness of allogeneic NK cells immunotherapy on HIV-1 immunological non-responders (INRs) receiving antiretroviral therapy (ART).

Methods: From February to April 2018, a prospective, randomized, controlled, open-label clinical trial, which enrolled 20 HIV-1 INRs following specific inclusion criteria, was conducted at Nankai University Second People's Hospital. Participants were randomly allocated (simple randomization 1:1) to either the combined treatment (NK + ART) group (n = 10) or the control (ART) group (n = 10). The allogenic highly activated NK cells from killer cell immunoglobulin-like receptor (KIR)/human leukocyte antigen (HLA)-Cw mismatched healthy donor were prepared (10 cells in each injection) and intravenously infused to each recruited patient of NK+ART group in three courses. Key immune parameters (CD4 count, CD8 count, CD4/CD8 ratio), laboratory tests (count of blood cells, biochemistry panel) and symptoms at baseline and at month 1, 3, 6, 9, 12, and 24 were measured/collected to analyze the safety and efficacy of the therapy. Comparisons were between the seven time-points of both groups using repeated measurement analysis of variance (ANOVA) test. Generalized estimating equations (GEE) model was performed to evaluate the overall effect of the NK+ART group vs. the ART group.

Results: From baseline to 24 months, we noted a mean CD4 count augmentation (139 to 243 cells/μL) in the NK + ART group and (144 to 176 cells/μL) in the ART group (difference, 67; 95% CI, 10 to 124; P = 0.024). Our estimations revealed that NK+ART group could improve CD4 level (β = 54.59, P = 0.006) and CD8 level (β = 322.47, P = 0.010) on average among the six measurements compared with the ART group. Only two (2/10, 20%) participants in the NK+ART group developed a transient mild fever after the first course.

Conclusions: This preliminary study informs that HIV-1 INRs, allogenic NK cells immunotherapy is safe and could significantly improve CD4 recovery but not CD4/CD8 ratio. The practical effects, however, need long-term follow-up observations. Further study on the potential underlying mechanism is warranted. REGISTRATION INFO:: www.chictr.org.cn/showproj.aspx?proj=34912 (No. ChiCTR1900020634).
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http://dx.doi.org/10.1097/CM9.0000000000001189DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7717728PMC
December 2020

Increased early activation of CD56dimCD16dim/- natural killer cells in immunological non-responders correlates with CD4+ T-cell recovery.

Chin Med J (Engl) 2020 Nov 25;133(24):2928-2939. Epub 2020 Nov 25.

Center for Infectious Diseases, Beijing Youan Hospital, Capital Medical University, Beijing 100069, China.

Background: Natural killer (NK) cells play a critical role in suppressing human immunodeficiency virus-1 (HIV-1) infection, but knowledge on whether and how NK cells affect immune reconstitution in HIV-1-infected individuals who receive antiretroviral therapy (ART) is limited.

Methods: We performed a case-control study with 35 healthy individuals and 66 HIV-1-infected patients including 32 immunological non-responders (INRs) with poor CD4+ T-cell recovery (<500 cells/μL after 4 years of ART) and 34 immunological responders (IRs) with improved CD4+ T-cell recovery (>500 cells/μL after 4 years of ART). NK cell phenotype, receptor repertoire, and early activation in INRs and IRs were investigated by flow cytometry.

Results: A significantly higher proportion of CD56dimCD16dim/- NK cells was observed in INRs than IRs before ART and after 4 years of ART. The number of CD56dimCD16dim/- NK cells was inversely correlated with CD4+ T-cell counts in INRs before ART (r = -0.344, P = 0.050). The more CD69-expressing NK cells there were, the lower the CD4+ T-cell counts and ΔCD4, and these correlations were observed in INRs after ART (r = -0.416, P = 0.019; r = -0.509, P = 0.003, respectively). Additionally, CD69-expressing CD56dimCD16dim/- NK cells were more abundant in INRs than those in IRs (P  = 0.018) after ART, both of which had an inverse association trend towards significance with CD4+ T-cell counts. The expression of the activating receptors NKG2C, NKG2D, and NKp46 on CD56dimCD16dim/- NK cell subsets were higher in IRs than that in INRs after 4 years of ART (all P < 0.01). Strong inverse correlations were observed between CD69 expression and NKG2C, NKG2A-NKG2C+, NKG2D, and NKp46 expression on CD56dimCD16dim/- NK cells in INRs after ART (NKG2C: r = -0.491, P = 0.004; NKG2A-NKG2C+: r = -0.434, P = 0.013; NKG2D: r = -0.405, P = 0.021; NKp46: r = -0.457, P = 0.008, respectively).

Conclusions: INRs had a larger number of CD56dimCD16dim/- NK cells characterized by higher activation levels than did IRs after ART. The increase in the CD56dimCD16dim/- NK cell subset may play an adverse role in immune reconstitution. Further functional studies of CD56dimCD16dim/- NK cells in INRs are urgently needed to inform targeted interventions to optimize immune recovery.
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http://dx.doi.org/10.1097/CM9.0000000000001262DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7752673PMC
November 2020

Structure, property, biogenesis, and activity of diterpenoid alkaloids containing a sulfonic acid group from .

Acta Pharm Sin B 2020 Oct 27;10(10):1954-1965. Epub 2020 Jan 27.

State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.

Three new C-diterpenoid alkaloids with a sulfonic acid unit, named aconicarmisulfonines B and C ( and ) and chuanfusulfonine A (), respectively, were isolated from the lateral roots ("fu zi" in Chinese). Structures of - were determined by spectroscopic data analysis. Intriguing chemical properties and reactions were observed for the C-diterpenoid alkaloids: (a) specific selective nucleophilic addition of the carbonyl (C-12) in with CDOD; (b) interconversion between and in DO; (c) stereo- and/or regioselective deuterations of H-11 in - and both H-11 and H-11 in aconicarmisulfonine A (); (d) TMSP-2,2,3,3- promoted cleavage of the C-12-C-13 bond of in DO; (e) dehydrogenation of in pyridine-, and (f) NaSO-assisted dehydrogenation and -deethylation of songorine (, a putative precursor of -). Biogenetically, and are correlated with , for which the same novel carbon skeleton is proposed to be derived from semipinacol rearrangements migrations of C-13-C-16 and C-15-C-16 bonds of the napelline-type skeleton, respectively. Meanwhile, is a highly possible precursor or a concurrent product in the biosynthetic pathways of , , and . In the acetic acid-induced mice writhing assay, at 1.0 mg/kg (i.p.), compounds , , , , and exhibited analgesic effects against mice writhing.
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http://dx.doi.org/10.1016/j.apsb.2020.01.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7606178PMC
October 2020

Denisovan DNA in Late Pleistocene sediments from Baishiya Karst Cave on the Tibetan Plateau.

Science 2020 10;370(6516):584-587

Key Laboratory of Vertebrate Evolution and Human Origins of Chinese Academy of Sciences, Institute of Vertebrate Paleontology and Paleoanthropology, CAS, Beijing 100044, China.

A late Middle Pleistocene mandible from Baishiya Karst Cave (BKC) on the Tibetan Plateau has been inferred to be from a Denisovan, an Asian hominin related to Neanderthals, on the basis of an amino acid substitution in its collagen. Here we describe the stratigraphy, chronology, and mitochondrial DNA extracted from the sediments in BKC. We recover Denisovan mitochondrial DNA from sediments deposited ~100 thousand and ~60 thousand years ago (ka) and possibly as recently as ~45 ka. The long-term occupation of BKC by Denisovans suggests that they may have adapted to life at high altitudes and may have contributed such adaptations to modern humans on the Tibetan Plateau.
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http://dx.doi.org/10.1126/science.abb6320DOI Listing
October 2020

Selenium Regulation of the Immune Function of Dendritic Cells in Mice Through the ERK, Akt and RhoA/ROCK Pathways.

Biol Trace Elem Res 2020 Oct 26. Epub 2020 Oct 26.

Immune Cells and Antibody Engineering Research Center of Guizhou Province/Key Laboratory of Biology and Medical Engineering, Guizhou Medical University, Guiyang, Guizhou, China.

Selenium levels can regulate the function of T cells, macrophages, B cells, natural killer cells and other immune cells. However, the effect of selenium on the immune function of dendritic cells (DCs) isolated from selenium-supplemented mice is unknown. In this study, C57BL/6J mice were randomly divided into three groups and fed diets containing low (0.08 ppm), medium (0.25 ppm) or high (1 ppm) selenium levels for 8 weeks. Immature (imDCs) and mature (mDCs) dendritic cells were then isolated from the bone marrow. Next, the migration, phagocytic capacity and mixed lymphocyte reaction (MLR) for imDCs and mDCs were detected by transwell and flow cytometry. The levels of C-C chemokine receptor type 7 (CCR7), major histocompatibility complex II (MHCII) and reactive oxygen species (ROS) were assayed by flow cytometry. F-actin and superoxide dismutase (SOD) activity was detected by fluorescence microscopy and SOD assay kit, respectively. In addition, the extracellular signal-regulated kinase (ERK), Akt, Ras homolog gene family member A/Rho-associated protein kinase (RhoA/ROCK) signalling, selenoprotein K (SELENOK) and glutathione peroxidase 1 (GPX1) levels were measured by western blot analysis. The results indicated that selenium deficiency enhanced the migration of imDCs by ROS and SELENOK-mediated ERK, Akt and RhoA/ROCK pathways but impaired the antigen uptake of imDCs. Although a high selenium level inhibited the migration of imDCs, it had no effect on phagocytic capacity. For mDCs, low selenium levels impaired free migration, and high levels inhibited the chemotactic migration involved in F-actin and CCR7, respectively. Low and high selenium levels impaired the MLR by inhibiting MHCII surface localisation, which might be related to ROS- and SELENOK-mediated ERK, Akt and RhoA/ROCK signalling pathways. In summary, selenium may regulate the immune function of mouse DCs through the ROS- and SELENOK-mediated ERK, Akt and RhoA/ROCK signalling.
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http://dx.doi.org/10.1007/s12011-020-02449-5DOI Listing
October 2020

HIV Gene Therapy Strategies and Safety: What do we know from the Recent Publications?

AIDS Rev 2020 10 26;23(3):195-202. Epub 2020 Oct 26.

Department of Infectious Diseases, Tianjin Second People's Hospital, Tianjin Association of STD/AIDS Prevention and Control; School of Medicine, Nankai University. Tianjin, China.

Almost 40 years ago, the world was noticing the emergence of one of the major public health threats it has ever known: HIV. Facing the cost-effectiveness and the health-related issues encountered with antiretroviral treatments, scientists have imagined and conceived gene therapies to tackle HIV infection. The success of such an approach was proved with the "Berlin" patient then recently reiterated in the "London" patient. In fact, the recent progress made in HIV gene therapy could provide a rapid emergence of powerful strategies to treat and totally cure the infection. Based on their principles, these approaches can be separated in three strategies that are (1) engineering HIV target cells to render them resistant to HIV replication, (2) generating genemodified cells able to secrete antiviral proteins that interfere with HIV entry, and (3) modifying cytotoxic T cells to selectively target and eliminate infected cells. Herein, we proposed to review these approaches, their safety and their benefits as reported in recent publications.
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http://dx.doi.org/10.24875/AIDSRev.20000008DOI Listing
October 2020

[Corrigendum] Preliminary research on the effects and mechanisms of umbilical cord‑derived mesenchymal stem cells in streptozotocin‑induced diabetic retinopathy.

Int J Mol Med 2020 11 25;46(5):1938. Epub 2020 Aug 25.

Department of Ophthalmology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China.

Following the publication of this article, the authors have realized that grant number published in the 'Funding' section of their paper was written incorrectly: The grant number for the support the authors received from the Health Commission of Hubei Province Scientific Research Project should have been written as 'WJ2019F038' instead of 'WJ2009F038'. The authors apologize to the funders of their research project, and to the readership of the Journal for any inconvenience caused. [the original article was published in International Journal of Molecular Medicine 46: 849‑858, 2020; DOI: 10.3892/ijmm.2020.4623].
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http://dx.doi.org/10.3892/ijmm.2020.4708DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7521547PMC
November 2020

Metal-Organic Frameworks: A Potential Platform for Enzyme Immobilization and Related Applications.

Front Bioeng Biotechnol 2020 30;8:695. Epub 2020 Jun 30.

School of Chemistry and Chemical Engineering, Guangdong Provincial Key Lab of Green Chemical Product Technology, South China University of Technology, Guangzhou, China.

Enzymes, as natural catalysts with remarkable catalytic activity and high region-selectivities, hold great promise in industrial catalysis. However, applications of enzymatic transformation are hampered by the fragility of enzymes in harsh conditions. Recently, metal-organic frameworks (MOFs), due to their high stability and available structural properties, have emerged as a promising platform for enzyme immobilization. Synthetic strategies of enzyme-MOF composites mainly including surface immobilization, covalent linkage, pore entrapment and synthesis. Compared with free enzymes, most immobilized enzymes exhibit enhanced resistance against solvents and high temperatures. Besides, MOFs serving as matrixes for enzyme immobilization show extraordinary superiority in many aspects compared with other supporting materials. The advantages of using MOFs to support enzymes are discussed. To obtain a high enzyme loading capacity and to reduce the diffusion resistance of reactants and products during the reaction, the mesoporous MOFs have been designed and constructed. This review also covers the applications of enzyme-MOF composites in bio-sensing and detection, bio-catalysis, and cancer therapy, which is concerned with interdisciplinary nano-chemistry, material science and medical chemistry. Finally, some perspectives on reservation or enhancement of bio-catalytic activity of enzyme-MOF composites and the future of enzyme immobilization strategies are discussed.
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http://dx.doi.org/10.3389/fbioe.2020.00695DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7338372PMC
June 2020

[A new lignan glucoside from root of Paeonia lactiflora].

Zhongguo Zhong Yao Za Zhi 2020 Jun;45(12):2903-2906

State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica,Chinese Academy of Medical Sciences and Peking Union Medical College Beijing 100050, China.

A new lignan glucoside,(+)-fragransin A_2-4-O-β-D-glucopyranoside(1), has been isolated from the dry root of Paeonia lactiflora by column chromatography on silica gel, Sephadex LH-20, and MCI-gel resin, as well as preparative RP-HPLC. The structure of the new compound was elucidated by spectroscopic data analysis(MS, UV, IR, CD, 1 D and 2 D NMR) and chemical method. Compound 1 showed moderate inhibition against lipopolysaccharide induced nitric oxide production in RAW264.7 macrophages, with an IC_(50) value of 21.3 μmol·L~(-1).
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http://dx.doi.org/10.19540/j.cnki.cjcmm.20200328.203DOI Listing
June 2020

Preliminary research on the effects and mechanisms of umbilical cord‑derived mesenchymal stem cells in streptozotocin‑induced diabetic retinopathy.

Int J Mol Med 2020 Aug 1;46(2):849-858. Epub 2020 Jun 1.

Department of Ophthalmology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China.

Diabetic retinopathy (DR) is one of the most prevalent microvascular complications of diabetes, and a common cause of blindness in working‑age individuals. Mesenchymal stem cell (MSC) transplantation has been considered a promising intervention therapy for DR, wherein the differentiation of MSCs into nerve cells plays an essential role. However, research into the role of MSCs in DR treatment remains incomplete, and the mechanisms of retinal repair at the molecular level have yet to be clarified. In the present study, all‑trans retinoic acid (ATRA) was used to promote the proliferation of rat umbilical cord (UC)‑derived MSCs and their differentiation into nerve cells. Furthermore, the effects and mechanisms of UC‑MSCs with or without ATRA treatment were investigated in rats subjected to streptozocin (STZ)‑induced DR. The results demonstrated that the transplantation of UC‑MSCs treated with or without ATRA attenuated DR in rats, and alleviated retinal tissue damage and apoptosis. In addition, the transplantation of UC‑MSCs treated with or without ATRA attenuated angiogenesis and inflammation in the retina by regulating the levels of relevant cytokines. UC‑MSCs treated with ATRA exerted a more prominent therapeutic effect than the untreated UC‑MSCs. On the whole, these findings indicate that UC‑MSCs alleviate STZ‑induced DR in rats by regulating angiogenesis and the inflammatory response at the molecular level. Thus, the findings of the present study may provide a theoretical basis for the application of MSCs in the treatment of DR.
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http://dx.doi.org/10.3892/ijmm.2020.4623DOI Listing
August 2020

Community-acquired pneumonia caused by methicillin-resistant Staphylococcus aureus in a Chinese adult: A case report.

Medicine (Baltimore) 2020 Jun;99(26):e20914

Department of Respiratory Medicine.

Rationale: Methicillin-resistant Staphylococcus aureus (MRSA) has been established as an important cause of severe community-acquired pneumonia (CAP) with very high mortality. Panton-Valentine leukocidin (PVL) producing MRSA has been reported to be associated with necrotizing pneumonia and worse outcome. The incidence of community-acquired MRSA (CA-MRSA) pneumonia is very low, as only a few CA-MRSA pneumonia cases were reported in the last few years. We present a case of severe CAP caused by PVL-positive MRSA with ensuing septic shock.

Patient Concerns: A 68-year-old male with no concerning medical history had developed a fever that reached 39.0°C, a productive cough that was sustained for 5 days, and hypodynamia. He was treated with azithromycin and alexipyretic in a nearby clinic for 2 days in which the symptoms were alleviated. However, 1 day later, the symptoms worsened, and he was taken to a local Chinese medicine hospital for traditional medicine treatment. However, his clinical condition deteriorated rapidly, and he then developed dyspnea and hemoptysis.

Diagnosis: CA-MRSA pneumonia and septic shock. The sputum culture showed MRSA. Polymerase chain reaction of MRSA isolates was positive for PVL genes.

Interventions: Mechanical ventilation, fluid resuscitation, and antibiotic therapy were performed. Antibiotic therapy included mezlocillin sodium/sulbactam sodium, linezolid, and oseltamivir.

Outcomes: He died after 12 hours of treatment.

Lessons: This is a report of severe pneumonia due to PVL-positive CA-MRSA in a healthy adult. CA-MRSA should be considered a pathogen of severe CAP, especially when combined with septic shock in previously healthy individuals.
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http://dx.doi.org/10.1097/MD.0000000000020914DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7329007PMC
June 2020

The Challenge of Potential Drug-Drug Interactions Among People Living With HIV on Antiretroviral Therapy: A Cross-Sectional Study in Selected Provinces in China.

Front Pharmacol 2020 27;11:800. Epub 2020 May 27.

Department of Infectious Diseases, Beijing Youan Hospital, Capital Medical University, Beijing, China.

Objectives: Potential drug-drug interactions (DDIs) are a significant therapeutic threat among human immunodeficiency virus (HIV)-positive individuals on antiretroviral (ARV) medications. DDIs involving ARV drugs in mainland China are unknown and insufficiently described. Herein, we investigated the prevalence and frequencies of potential ARV DDIs in Chinese people living with HIV (PLWH), then we assessed the risk factors associated with potential DDIs.

Methods: This study was conducted with HIV-positive adults undergoing ARV medications from multiple centers across China. The latest prescription of each participant was evaluated for potential DDIs using the Liverpool HIV drug interaction database. Multivariable logistic regressions were used to evaluate the factors associated with DDIs.

Results: Among 600 PLWH recruited, at least one non-HIV co-medication was observed in 511 (85.2%) individuals. A total of 2566 DDIs were identified, of which 11 (0.43%) and 311 (12.89%) were of contraindicated (red-flags) and dosage/timing adjustment required (orange-flags), respectively. Multivariate regression analysis revealed a higher risk of clinically significant DDIs (red- and orange-flagged comedication) associated with: the use of boosted protease inhibitors ( < 0.0001), boosted integrase strand transfer inhibitors ( < 0.0001), and non-nucleoside reverse transcriptase inhibitors-based ARV regimen ( < 0.0001); or the use of antiinfectives for systemic use ( < 0.0001), cardiovascular system drugs ( < 0.0001), nervous system drugs ( < 0.0001), fungal infection ( = 0.0071), and virus infection ( = 0.0231).

Conclusions: Potential DDIs and inappropriate medications constitute a burden for people living with HIV in China. The knowledge of DDIs patterns and the scan for DDIs is crucial. Indeed, they can help to prevent drug-related adverse outcomes in such immunodeficient population.
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http://dx.doi.org/10.3389/fphar.2020.00800DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7266979PMC
May 2020

Efficacy and Safety of Direct-Acting Antiviral Therapy in Patients With Chronic Hepatitis C Virus Infection: A Real-World Single-Center Experience in Tianjin, China.

Front Pharmacol 2020 19;11:710. Epub 2020 May 19.

Department of Infectious Disease, Tianjin Second People's Hospital, Tianjin, China.

Objective: Toward the limited real-world data concerning the treatment response to brand direct-acting antiviral agents (DAAs) therapy, we proposed to evaluate the efficacy and safety of DAAs for the treatment of chronic hepatitis C virus (HCV) in mainland China.

Methods: In this retrospective, single-center, cohort study, all HCV-infected adult patients treated with brand DAA drugs covered by Tianjin local health insurance (Apr 2018-Sept 2019) and responding to other specific inclusion criteria were recruited. The five available DAA regimens included sofosbuvir + ribavirin (SOF + RBV), elbasvir/grazoprevir (EBR/GZR), ombitasvir/paritaprevir/ritonavir/dasabuvir (OBV/PTV/r/DSV) ± RBV, daclatasvir + asunaprevir (DCV + ASV), and SOF + DCV ± RBV. Demographic, virologic, clinical, and adverse effects data obtained during and after DAAs treatment were collected. We evaluated the rate of sustained virological response at 12 weeks post-treatment (SVR12), the incidence of adverse effects, and assessed the factors associated with SVR12.

Results: Four hundred ninety-four patients finished the treatment and completed the 12-week post-treatment follow-up. The overall SVR12 rate was estimated at 96.96%. SVR rates greater than 95% were achieved in most of the HCV genotypes with the exception of GT1a (0%), GT3a (93.33%), and GT3b (88.24%). SVR12 for patients treated with DCV + ASV, EBR/GZR, OBV/PTV/r/DSV ± RBV, SOF + DCV ± RBV, and SOF + RBV for 12 or 24 weeks was 86.67%, 100%, 98.11%, 97.56%, and 95.06%, respectively. Subjects with compensated cirrhosis (92.73%) and prior treatment experience (77.78%) had significantly lower SVR rates when compared to chronic hepatitis C (98.15%) and treatment-naive (97.69%) groups. In Tianjin, the available DAA regimens were generally well-tolerated, and not a single serious adverse event was reported.

Conclusion: In this large real-life single-center HCV cohort from China, oral DAAs were highly effective and well-tolerated. Further and larger-scale studies are needed to evaluate their clinical safety and efficacy.
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http://dx.doi.org/10.3389/fphar.2020.00710DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7248196PMC
May 2020

[Effect of Siegesbeckiae Herba in treating chronic pain].

Zhongguo Zhong Yao Za Zhi 2020 Apr;45(8):1851-1858

Dongzhimen Hospital, Beijing University of Chinese Medicine Beijing 100700, China.

The treatment of pain with complementary and alternative medicine has gradually attracted international attention. Traditional Chinese medicine(TCM) with clear composition and mechanism will become a new starting point for new drug research and development. Siegesbeckiae Herba is a commonly used TCM herb in the treatment of rheumatic arthralgia. With a clear chemical composition, Siegesbeckiae Herba has a long history of clinical application and a certain modern research basis in the treatment of chronic pain. It has good research and development prospects in the treatment of analgesia. Based on the occurrence principle of pain and the known mechanism of action of Siegesbeckiae Herba, we discussed the advance of studies on Siegesbeckiae Herba in three aspects, namely inflammatory pain, neuropathic pain and cancer pain, so as to provide reference for further basic research and development and application of new TCM.
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http://dx.doi.org/10.19540/j.cnki.cjcmm.20191016.501DOI Listing
April 2020

Yanhusanines A-F, Isoquinoline-Derived Alkaloid Enantiomers from and Their Biological Activity.

J Nat Prod 2020 02 14;83(2):489-496. Epub 2020 Feb 14.

State Key Laboratory of Bioactive Substance and Function of Natural Medicines , Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College , Beijing 100050 , People's Republic of China.

Six new pairs of isoquinoline alkaloid enantiomers, designated as yanhusanines A-F (-), were isolated from an aqueous extract of tubers. The structures of these enantiomers were elucidated via physicochemical analysis and a variety of spectroscopic methods. All compounds were resolved into their enantiomers via chiral-phase HPLC, and their configurations were determined by DP4+ NMR calculation methods, specific rotations, and comparison of experimental and calculated ECD spectra. Compounds - bear a rare 9-methyl moiety, and compound possesses a rare 1-oxa-6-azaspiro[4.5]decane core containing an -CHO group. Compounds (+)-, (-)-, (+)-, (-)-, (+)-, (-)-, (+)-, and (-)- exhibited selective inhibitory activities against human carboxylesterase (hCE2), in the IC value range of 2.0-13.2 μM.
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http://dx.doi.org/10.1021/acs.jnatprod.9b01155DOI Listing
February 2020

6'-O-galloylpaeoniflorin regulates proliferation and metastasis of non-small cell lung cancer through AMPK/miR-299-5p/ATF2 axis.

Respir Res 2020 Feb 3;21(1):39. Epub 2020 Feb 3.

Department of Respiratory Medicine, Key Laboratory of Organ Regeneration and Transplantation of the Ministry of Education, First Hospital of Jilin University, Changchun, Jilin Province, China.

Background: Recent studies have shown 6'-O-galloylpaeoniflorin (GPF), a nature product extracted from the roots of paeoniflorin exerts anti-oxidant and anti-inflammatory activities. However, the effects of GPF on the proliferation and invasion in non-small cell lung cancer (NSCLC) cells have not been clarified.

Methods: MTT assay was performed to determine the cytotoxicity of GPF treatment on NSCLC cells. Colony formation assay, cell scratch test and transwell assay were performed to determine the proliferation and invasion of NSCLC cells in vitro, respectively. An A549 cell xenograft mouse model was performed to confirm the growth of NSCLC cells in vivo. Western blotting was used to measure the levels of activating transcription factor 2 (ATF2), AMP-activated protein kinase (AMPK) and phosph-AMPK (p-AMPK). Luciferase assay was used to validate the binding of miR-299-5p on the 3' untranslated region (UTR) of ATF2.

Results: Administration of GPF (50 or 100 μM) was significantly cytotoxic to A549 cells and H1299 cells, as well as inhibited the clonality, invasion and metastasis of NSCLC cells in vitro. GPF treatment also inhibited the tumor growth of NSCLC cell mouse xenografts in vivo. Exotic expression of miR-299-5p significantly inhibited the growth of NSCLC cells in vitro and in vivo. Downregulation of miR-299-5p expression attenuated the inhibition of the proliferation and metastasis of non-small cell lung cancer cells by GPF treatment. miR-299-5p significantly decreased ATF2 mRNA and protein levels in A549 cells (p < 0.05). Overexpression of ATF2 blocked the inhibitory effect of miR-299-5p on the proliferation and invasiveness of A549 cells.

Conclusions: GPF regulates miR-299-5p/ATF2 axis in A549 cells via the AMPK signalling pathway, thereby inhibiting the proliferation and metastasis of non-small cell lung cancer cells.
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http://dx.doi.org/10.1186/s12931-020-1277-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6998290PMC
February 2020

Decreased ratio of influenza-specific IgG versus IgM in response to influenza vaccination in antiretroviral-treated HIV-infected African Americans compared to Caucasians, and its direct correlation with the percentages of peripheral Tfh cells.

Vaccine 2020 02 14;38(8):1998-2004. Epub 2020 Jan 14.

Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, SC 29425, USA; Division of Infectious Diseases, Department of Medicine, Medical University of South Carolina, Charleston, SC 29425, USA. Electronic address:

Background: Racial differences have been observed in the rate of bacterial infection and disease progression in HIV. Here, we evaluate racial differences in seasonal influenza vaccine responses.

Methods: 16 healthy controls (9 Caucasians (CC) and 7 African Americans (AA)) and 26 antiretroviral therapy (ART)-treated aviremic HIV+ subjects (11 CC and 15 AA) were enrolled in the current study. Blood was collected at pre-vaccination (D0) and day 14 (D14) following seasonal influenza vaccination. Serologic responses were characterized in plasma by ELISA. B and T cells were assessed by flow cytometry ex vivo.

Results: The absolute counts of CD4+ CD3+ T cells and CD19+ B cells were similar in healthy controls and HIV-infected individuals, and similar in CC and AA in the two study groups. However, the percentage of peripheral T follicular helper (pTfh) cells was decreased in HIV+ AA compared to HIV+ CC. There were no racial differences in IgG antibody responses against vaccination in the two study groups. However, the ratio of anti-influenza-specific IgG versus IgM induction following vaccination was decreased in HIV+ AA compared to HIV+ CC, which was directly correlated with the percentages of pTfh cells. This racial difference and correlation were not demonstrable in healthy controls.

Conclusion: Here we report that HIV + AA has decreased fold induction of IgG versus IgM after influenza vaccination, which may suggest impaired class-switching from IgM to IgG in AA HIV-infected individuals.
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http://dx.doi.org/10.1016/j.vaccine.2020.01.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7333243PMC
February 2020