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1.
Journal of Chinese Physician ; (12): 178-185, 2023.
Article in Chinese | WPRIM | ID: wpr-992280

ABSTRACT

Objective:To analyze the mechanism of Danpi-Chishao in treatment of sepsis based on network pharmacology.Methods:The corresponding targets of Danpi-Chishao and sepsis were carried out through TCMSP database, OMIM database and Genecards database. Cystoscope 3.8.2 software was used to construct the " Chinese medicine-active components-target-disease" network diagram. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were carried out by DAVID database. Weisheng cloud platform was used to draw bubble map.Results:A total of 36 effective components of Danpi-Chishao was obtained, mainly including quercetin, kaempferol, baicalin, β-sitosterol, stigmasterol, paeoniflorin and so on. There were 96 potential common key targets between Danpi-Chishao and sepsis, such as prostaglandin-endoperoxide synthase 2 (PTGS2), transcription factor p65 (RELA), phosphatidylinositol-4, 5-bisphosphate 3-kinase catalytic subunit gamma (PIK3CG), B-cell lymphoma 2 (BCL-2)-associated X (BAX), BCL-2, Caspase-3 (CASP3) with a degree value>4.9. The result of protein-protein interaction (PPI) network analysis showed that there were 10 important target proteins, including alpha serine/threonine-protein kinase (AKT1), interleukin-6 (IL-6), tumor necrosis factor (TNF), interleukin-1β (IL-1β), vascular endothelial growth factor A (VEGFA), cellular tumor antigen p53 (TP53), matrix metalloproteinase-9 (MMP9), CASP3, PTGS2, C-C motif chemokine ligand 2 (CCL2). The pathways obtained by GO and KEGG enrichment analysis included atherosclerosis pathway, advanced glycation end products (AGE)-receptor for advanced glycation end products (RAGE) signal pathway, cancer pathway, tumor necrosis factor signal pathway, hypoxia-inducible factor (HIF) signal pathway, IL-17 signal pathway and other pathway.Conclusions:The mechanism of the intervention effect of Danpi-Chishao on sepsis may be that the active components such as quercetin, kaempferol, paeoniflorin act on target proteins such as PTGS2, RELA, PIK3CG, BAX, BCL2, CASP3, and through TNF-related signal pathway, HIF-1 signal pathway, IL-17 signal pathway, etc. Nonetheless, the conclusion needs further experimental verification.

2.
Acta Pharmaceutica Sinica B ; (6): 754-764, 2023.
Article in English | WPRIM | ID: wpr-971734

ABSTRACT

A chemical investigation on the aqueous extract of Corydalis yanhusuo tubers led to the isolation and structural elucidation of three pairs of trace enantiomeric hetero-dimeric alkaloids, (+)/(-)-yanhusamides A-C ( 1- 3), featuring an unprecedented 3,8-diazatricylco[5.2.2.02,6]undecane-8,10-diene bridged system. Their structures were exhaustively characterized by X-ray diffraction, comprehensive spectroscopic data analysis, and computational methods. Guided by the hypothetical biosynthetic pathway for 1- 3, a gram-scale biomimetic synthesis of (±)- 1 was achieved in 3 steps using photoenolization/Diels-Alder (PEDA) [4+2] cycloaddition. Compounds 1‒3 exhibited potent inhibition of NO production induced by LPS in RAW264.7 macrophages. The in vivo assay showed that oral administration of 30 mg/kg of (±)- 1 attenuated the severity of rat adjuvant-induced arthritis (AIA). Additionally, (±)- 1 induced a dose-dependent antinociceptive effect in the acetic acid-induced mice writhing assay.

3.
China Journal of Chinese Materia Medica ; (24): 614-624, 2023.
Article in Chinese | WPRIM | ID: wpr-970530

ABSTRACT

Chronic heart failure(CHF) is a series of clinical syndromes in which various heart diseases progress to their end stage. Its morbidity and mortality are increasing year by year, which seriously threatens people's life and health. The diseases causing CHF are complex and varied, such as coronary heart disease, hypertension, diabetes, cardiomyopathy and so on. It is of great significance to establish animal models of CHF according to different etiologies to explore the pathogenesis of CHF and develop drugs to prevent and treat CHF induced by different diseases. Therefore, based on the classification of the etiology of CHF, this paper summarizes the animal models of CHF widely used in recent 10 years, and the application of these animal models in traditional Chinese medicine(TCM) research, in order to provide ideas and strategies for studying the pathogenesis and treatment of CHF, and provide ideas for TCM modernization research.


Subject(s)
Animals , Medicine, Chinese Traditional , Heart Failure , Heart Diseases , Chronic Disease , Models, Animal
4.
Acta Pharmaceutica Sinica B ; (6): 1919-1955, 2023.
Article in English | WPRIM | ID: wpr-982828

ABSTRACT

Chronic heart failure (CHF) is a severe public health problem with increasing morbidity and mortality, any treatment targeting a single session is insufficient to tackle this. CHF is characterized by reduced cardiac output resulting from neurohumoral dysregulation and cardiac remodeling, which might be related to oxidative stress, inflammation, endoplasmic reticulum stress, apoptosis, autophagy, mitochondrial function, and angiogenesis. These molecular mechanisms interact with each other through crosstalk. Historically, Chinese medicinal herbs have been widely applied in the treatment of CHF, and therapeutic effects of Chinese medicinal herbs and their ingredients have been scientifically confirmed over the past decades. Traditional Chinese medicine (TCM) with multiple components can confront the different pathogenesis of CHF through multiple targets. This review analyzes commonly used TCM patent drugs and TCM decoctions that are applicable to different stages of CHF based on clinical trials. Diverse bioactive ingredients in Chinese medicinal herbs have been found to treat CHF via multiple molecular mechanisms. This review comprehensively covers the key works on the effects and underlying mechanisms of TCM, herbal ingredients and synergistic effects of constituent compatibility in treating CHF, providing additional ideas to address this threat.

5.
China Journal of Chinese Materia Medica ; (24): 1705-1729, 2022.
Article in Chinese | WPRIM | ID: wpr-928169

ABSTRACT

The traditional Chinese medicine(TCM) contains very complex constituents. Besides the major constituents, there are a large number of unclear trace constituents with novel skeletons and potent bioactivities, which have been regarded as one of the important therapeutic substances and the great resources of innovative drugs derived from TCM. The present review highlighted that the development of the trace therapeutic substances of TCM is closely depends on the advanced technologies for their identification, isolation, structure elucidation, and bioactivity evaluation. Additionally, this paper reviewed the novel trace compounds derived from Chinese herbal medicines which have been published in Organic Letters during 2001-2021, and summarized the important licensed drugs originated from the trace therapeutic substances and the discovery and development of trace therapeutic substances of 8 kinds of Chinese herbal medicines. This review provides references for the research and development of TCM therapeutic substances and innovative drugs.


Subject(s)
Drugs, Chinese Herbal/therapeutic use , Medicine, Chinese Traditional
6.
Chinese Journal of Natural Medicines (English Ed.) ; (6): 210-214, 2022.
Article in English | WPRIM | ID: wpr-929253

ABSTRACT

Two new neolignans and one new lignan (1-3) were obtained from the roots of Paeonia lactiflora. Their structures were unambiguously elucidated based on extensive spectroscopic analysis, single-crystal X-ray crystallography, and the calculated and experimental electronic circular dichroism (ECD) spectra. Compound 1 was a racemic mixture and successfully resolved into the anticipated enantiomers via chiral-phase HPLC. Compound 3 demonstrated moderate inhibitory activity against human carboxylesterase 2A1 (hCES2A1) with an IC50 value of 7.28 ± 0.94 μmol·-1.


Subject(s)
Humans , Chromatography, High Pressure Liquid , Lignans/chemistry , Paeonia , Plant Roots/chemistry , Stereoisomerism
7.
Journal of Experimental Hematology ; (6): 181-187, 2021.
Article in Chinese | WPRIM | ID: wpr-880050

ABSTRACT

OBJECTIVE@#To deeply understand the clinical manifestation, laboratory examination characteristics, diagnosis and treatment of an eight p11 myeloproliferative syndrome (EMS) with rare phenotypes.@*METHODS@#The clinical and laboratory characteristics and the process of allogeneic hematopoietic stem cell transplantation (allo-HSCT) were summarized in 1 rare EMS case involving T/B/myeloid cells. Meanwhile, 2 similar cases in the previous literature were also discussed.@*RESULTS@#The bone marrow examination indicated that the patient with B-cell acute lymphocytic leukemia. The lymph node biopsy showed that the patient was T lymphoblastic/myeloid lymphoma. The 8p11 abnormality was found by the examination of bone marrow chromosomes. The RT-PCR examination showed that the BCR-ABL fused gene was negtive. The FGFR1 breakage was found by using the FISH with FGFR1 probe in lymph node. The Mutation of FMNL3, NBPF1 and RUNX1 genes was found by using the whole exome sequencing. The patient received allo-HSCT under CR2. By the follow-up till to September 2019, the patient survived without the above-mentioned disease.@*CONCLUSION@#EMS manifest as neoplasms involving T-lineage, B-lineage, and myeloid-lineage simultaneously is extremely rare. Although the FGFR1 gene-targeted therapy can be conducted, allo-HSCT should be actively considered.


Subject(s)
Humans , Bone Marrow , Chromosomes, Human, Pair 8 , Formins , Hematologic Neoplasms , Myeloproliferative Disorders/genetics , Phenotype , Receptor, Fibroblast Growth Factor, Type 1/genetics , Translocation, Genetic
8.
Acta Pharmaceutica Sinica ; (12): 553-556, 2021.
Article in Chinese | WPRIM | ID: wpr-873782

ABSTRACT

(±)-Bicoryanhunine B (1), a new dimeric benzylisoquinoline alkaloid was isolated from the dried tubers of Corydalis yanhusuo by various chromatographic methods, including silica gel, Sephadex LH-20, reverse phase C18, and semi-preparative HPLC. Its structure was determined by spectroscopic methods, including UV, IR, ESI-MS, HR-ESI-MS and 1D/2D NMR. (±)-Bicoryanhunine B (1) was a moderate PD-1/PD-L1 interaction inhibitor with an IC50 value of 7.80 ± 0.49 μmol·L-1. In addition, 1 exhibited potent inhibitory activities against LPS-induced NO production in RAW 264.7 macrophages with an IC50 value of 4.83 ± 2.21 μmol·L-1.

9.
China Journal of Chinese Materia Medica ; (24): 2837-2842, 2021.
Article in Chinese | WPRIM | ID: wpr-887957

ABSTRACT

A new phenolic acid ester, 4'-hydroxyphenylethyl 4,8(R)-dihydroxyphenylpropionate(1), was isolated from an endophytic fungus Colletotrichum capsici of Paeonia lactiflora roots, along with eight known phenolic derivatives, tyrosol(2), 2-(4-hydroxyphenyl) ethyl acetate(3), methyl p-hydroxyphenylacetate(4), methyl m-hydroxyphenylacetate(5), 4-(4-hydroxyphene-thoxy)-4-oxobutanoic acid(6), 4-hydroxyphenethyl methyl succinate(7), trichodenol B(8) and 4-hydroxyphenethyl 2-(4-hydroxyphenyl) acetate(9). Their structures were identified by a combination of high-resolution electrospray ionization mass spectrometry(HR-ESI-MS), nuclear magnetic resonance(NMR) spectroscopy, ultraviolet(UV) spectroscopy and electronic circular dichroism(ECD) spectroscopy. Compounds 2-9 were isolated from this fungus for the first time.


Subject(s)
Colletotrichum , Esters , Hydroxybenzoates , Paeonia
10.
Acta Pharmaceutica Sinica ; (12): 1096-1099, 2021.
Article in Chinese | WPRIM | ID: wpr-886997

ABSTRACT

Bidehydrocorydaline A (1), a new dimeric alkaloid of proberberine connected by a methylenedioxy group, was isolated from the vinegar-prepared Corydalis yanhusuo by various chromatographic methods, including column chromatography over macroporous adsorption resin and silica gel, reverse-phase MPLC, and semi-preparative HPLC. Its structure was determined by spectroscopic methods, including UV, IR, HR-ESI-MS, 1D and 2D NMR. Bidehydrocorydaline A (1) showed potent inhibitory activity against LPS-induced NO production in RAW 264.7 macrophages, with an IC50 value of 2.33 ± 0.57 μmol·L-1.

11.
Chinese Journal of Natural Medicines (English Ed.) ; (6): 796-800, 2021.
Article in English | WPRIM | ID: wpr-922762

ABSTRACT

In a continuing search for biological natural products with structure diversity from traditional Chinese herbs, five new sesquineolignans (1-5) were isolated from an ethyl acetate extract of the twigs of Litsea cubeba. Their structures were elucidated based on MS, 1D and 2D NMR spectroscopic data, as well as experimental electronic circular dichroism (ECD) spectra. Compounds 1-5 showed moderate inhibitory effects against LPS-induced NO production in RAW264.7 macrophages, with IC


Subject(s)
Litsea , Macrophages , Molecular Structure
12.
Chinese Medical Journal ; (24): 2850-2856, 2021.
Article in English | WPRIM | ID: wpr-921172

ABSTRACT

BACKGROUND@#Central nervous system (CNS) symptoms after efavirenz (EFV) treatment in people living with human immunodeficiency virus (HIV) could persist and impact their quality of life. We assessed the impact of EFV-based regimen replacement with elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF), which is considered an alternative option for subjects who do not tolerate EFV. Most specifically, we assessed the safety and the efficacy of E/C/F/TAF and its effects on the participants' neuropsychiatric toxicity symptoms in a real-life setting.@*METHODS@#A prospective cohort study was conducted among virologic suppressed HIV-positive participants receiving EFV-based regimens with ongoing CNS toxicity ≥ grade 2. The participants were switched to single-pill combination regimens E/C/F/TAF and followed up for 48 weeks. The neuropsychiatric toxicity symptoms were measured using a CNS side effects questionnaire, as well as the Hospital Anxiety and Depression Scale and the Pittsburgh Sleep Quality Index. The primary outcome measure was the proportion of participants experiencing grade 2 or higher CNS toxicity after EFV switch off at weeks 12, 24, and 48. Secondary endpoints included virologic and immunological responses and the effect on fasting lipids at week 48 after switch.@*RESULTS@#One hundred ninety-six participants (96.9% men, median age: 37.5 years, median: 3.7 years on prior EFV-containing regimens) were included in the study. Significant improvements in anxiety and sleep disturbance symptoms were observed at 12, 24, and 48 weeks after switching to E/C/F/TAF (P < 0.05). No significant change in depression symptom scores was observed. At 48 weeks after switch, HIV viral load <50 copies/mL was maintained in all of the participants, median fasting lipid levels were moderately increased (total cholesterol [TC]: 8.2 mg/dL, low-density lipoprotein cholesterol [LDL-C]: 8.5 mg/dL, high-density lipoprotein cholesterol [HDL-C]: 2.9 mg/dL, and triglyceride (TG): 1.6 mg/dL, and the TC:HDL-C ratio remained stable.@*CONCLUSIONS@#The single-pill combination regimens E/C/F/TAF is safe and well tolerated. This study reveals that switching from EFV to E/C/F/TAF significantly reduces neuropsychiatric toxicity symptoms in people living with HIV with grade 2 or higher CNS complaints.


Subject(s)
Adult , Female , Humans , Male , Adenine/therapeutic use , Alanine , Alkynes , Anti-HIV Agents/adverse effects , Benzoxazines , Central Nervous System , Cobicistat/therapeutic use , Cyclopropanes , Drug Combinations , Emtricitabine/therapeutic use , HIV Infections/drug therapy , Prospective Studies , Quality of Life , Quinolones , Sleep Quality , Tenofovir/analogs & derivatives
13.
China Journal of Chinese Materia Medica ; (24): 5877-5883, 2020.
Article in Chinese | WPRIM | ID: wpr-878849

ABSTRACT

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.


Subject(s)
Acetates , Litsea , Monoterpenes , Sesquiterpenes
14.
China Journal of Chinese Materia Medica ; (24): 5866-5876, 2020.
Article in Chinese | WPRIM | ID: wpr-878848

ABSTRACT

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.


Subject(s)
Animals , Chronic Pain , Disease Models, Animal , Drugs, Chinese Herbal , Medicine, Chinese Traditional
15.
China Journal of Chinese Materia Medica ; (24): 5840-5865, 2020.
Article in Chinese | WPRIM | ID: wpr-878847

ABSTRACT

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.


Subject(s)
Humans , Analgesics/therapeutic use , Analgesics, Opioid/therapeutic use , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Biological Products/therapeutic use , Pain/drug therapy
16.
China Journal of Chinese Materia Medica ; (24): 5829-5839, 2020.
Article in Chinese | WPRIM | ID: wpr-878846

ABSTRACT

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.


Subject(s)
Humans , Aconitum , Alkaloids , Analgesics , Drugs, Chinese Herbal , Rhizome
17.
China Journal of Chinese Materia Medica ; (24): 2903-2906, 2020.
Article in Chinese | WPRIM | ID: wpr-828069

ABSTRACT

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).


Subject(s)
Chromatography, High Pressure Liquid , Glucosides , Lignans , Paeonia , Plant Extracts
18.
Chinese Medical Journal ; (24): 2803-2807, 2020.
Article in English | WPRIM | ID: wpr-877935

ABSTRACT

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).


Subject(s)
Humans , CD4 Lymphocyte Count , HIV Infections/therapy , HIV-1 , Hematopoietic Stem Cell Transplantation , Immunotherapy , Killer Cells, Natural , Prospective Studies , Viral Load
19.
Chinese Medical Journal ; (24): 2928-2939, 2020.
Article in English | WPRIM | ID: wpr-877928

ABSTRACT

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). 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.


Subject(s)
Humans , CD4 Lymphocyte Count , CD4-Positive T-Lymphocytes , Case-Control Studies , HIV Infections/drug therapy , HIV-1 , Killer Cells, Natural
20.
China Journal of Chinese Materia Medica ; (24): 119-124, 2019.
Article in Chinese | WPRIM | ID: wpr-771508

ABSTRACT

To explore the mechanism of β-carboline alkaloids inhibiting the migration and invasion of SGC-7901 cells and its correlation with FAK gene expression,CCK-8 method was used to determine the inhibitory rate of β-carboline alkaloids on the proliferation of gastric cancer SGC-7901 cells under different concentrations.The effect of β-carboline alkaloids on the migration and invasion of SGC-7901 cells was used by Transwell compartment.Detection of mRNA and protein expression of FAK genes were used by qRT-PCR and Western blot.Then si-FAK-1051 recombinant plasmid was transfected into SGC-7901 cells.FAK gene silencing effect was identified by qRT-PCR and Western blot technique again.Finally,the effects of FAK gene silencing on proliferation and migration of gastric cancer SGC-7901 cells were detected by CCK-8 kit and Transwell chamber assay respectively.With the increase of the concentration ofβ-carboline alkaloids,the inhibitory rate of SGC-7901 cells in human gastric cancer cells increased gradually,with IC5013.364 mg·L-1.The number of SGC-7901 cells of Transwell compartment in the positive experimental group(5-FU,5 mg·L-1) and the β-carboline alkaloids group decreased significantly(P<0.01) and the number of SGC-7901 cells in the β-carboline alkaloids group was significantly lower than that in the positive experimental group(P<0.01).Compared with the blank control group,the mRNA and protein expression level of FAK genes in the positive experimental group was significantly lower than that in the experimental group of β-carboline alkaloids(P<0.05).After transfection of si-FAK-1051 into gastric cancer SGC-7901 cells,the expression of mRNA and protein of FAK gene was significantly down regulated(P<0.05).SGC-7901 cell proliferation and cell migration ability also decreased significantly(P<0.05).β-carboline alkaloids are more effective than 5-FU in inhibiting migration and invasion of gastric cancer SGC-7901 cells,and the mechanism may be related to the inhibition of mRNA and protein expression of FAK gene by β-carboline alkaloids.


Subject(s)
Humans , Alkaloids , Pharmacology , Carbolines , Pharmacology , Cell Line, Tumor , Cell Movement , Cell Proliferation , Focal Adhesion Kinase 1 , Genetics , Gene Expression Regulation, Neoplastic , Gene Silencing , Neoplasm Invasiveness , Stomach Neoplasms , Drug Therapy , Pathology
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