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ObjectiveTo evaluate the expression level of DNA damage repair gene FANCI in hepatocellular carcinoma (HCC) and its relationship with prognosis, clinical stage and immune infiltration. MethodsIn this study, TCGA, GTEx, TIMER2.0, HPA database and qRT-PCR, western blot and immunohistochemistry were used to analyze the expression of FANCI in HCC and its correlation with different clinical stages; Kaplan-Meier Plotter database was used to explore the relationship between FANCI and the prognosis of HCC; the TISIDB database was used to analyze the relationship between FANCI and immune cell infiltration and immune checkpoints in HCC; the STRING database was used to detect the protein binding with FANCI; the TCGA and GTEx databases were used for GO and KEGG enrichment analysis; Cell experiments were used to explore the role of FANCI in HCC. ResultsCompared with normal tissues, the mRNA and protein expression levels of FANCI in tumor tissues were up-regulated (P<0.001); and HCC patients with high expression of FANCI had poor prognosis (P<0.001); the expression of FANCI in tumor tissues was positively correlated with the number of activated CD4+ T cells, the number of Th2 cells and the expression of immune checkpoints, and B-cell and macrophage infiltration was significantly lower in the FANCI high expression group (P<0.01); GO and KEGG enrichment analysis showed that FANCI-related genes were enriched in various biological processes such as amino acid transmembrane transporter activity; Cell experiments showed that knockdown of FANCI could inhibit the proliferation, invasion and migration of HCC (P<0.05). ConclusionsFANCI is highly expressed in hepatocellular carcinoma tissues, which may play a role in suppressing anti-tumor immunity and acting on pathways such as amino acid transmembrane transport, and is associated with poor prognosis. The proliferation, invasion and migration ability of hepatocellular carcinoma are inhibited after knocking down FANCI.
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Objective:To compare the effects of left bundle branch pacing(LBBP)and right ventricular pacing(RVP)on pacing threshold value,pacing perception,pacing impedance,QRS wave complex duration,interventricular mechanical delay(IVMD)time,left ventricular end diastolic diameter(LVEDD)and left ventricular ejection fraction(LVEF).Methods:The Chinese databases included China Biology Medicine Disc(CBMdisc),China National Knowledge Infrastructure(CNKI),Wanfang Database,China Science and Technology Journal Database,and foreign databases included PubMed,Cochrane library and Embase were adopted to retrieve research literatures about LBBP.The retrieval duration was from January 2018 to November 2021.The literatures were screened according to the inclusion and exclusion criteria of literatures,and the qualities of the literatures that met the inclusion criteria were respectively evaluated.The extracted relevant data of LBBP and RVP,which included pacing threshold value,pacing perception,pacing impedance,QRS wave complex duration,IVMD time,LVEDD and LVEF,were adopted to conduct Meta-analysis by using Revman5.4.Results:A total of 14 relevant literatures were included according to the inclusion and exclusion criteria of research literatures,which included 9 Chinese literatures and 5 English literatures.The duration of publication times of these literature was from 2018 to 2021.In these literatures,640 patients involved to LBBP and 551 patients involved to RVP.There were no significant differences between LBBP and RVP in the effects on pacing threshold value,pacing perception and pacing impedance[95%CI(-0.05-0.02),(-0.28-0.42),(-22.34-16.19),P>0.05],respectively.There were significant differences between LBBP and RVP in the effects on QRS wave complex duration,IVMD and LVEF[95%CI(-45.92--42.09),(-16.49--10.86),(3.01-5.13),P<0.05],respectively.There were two different results in the effects of LBBP and RVP on LVEDD.The five literatures among of them conducted effect size merging for the extracted LVEDD values.There was significant difference between two kinds of pacing methods in the effect on LVEDD[95%CI(-2.21--0.54),P<0.05].There was significant difference between two kinds of pacing methods in the effect on LVEDD after the literature(ShigengZhang2020)was excluded.Conclusion:The Meta-analysis about the application of LBBP in patients with bradyarrhythmia has demonstrated the effectiveness of LBBP.Compared with RVP,LBBP is more close to physiological pacing,and LBBP pacing parameters(threshold value,perception and impedance)are stable.
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To explore the characteristics of big data of patients with allergic rhinitis, including the time, population and spatial distribution of allergic rhinitis in Beijing from 2016 to 2021, so as to provide reference for the prevention and treatment of this disease. Descriptive epidemiological methods were used to analyze the distribution (including gender, age and location)and trend of allergic rhinitis patients in 30 pilot hospitals from January 2016 to December 2021, T test and Kruskal-Wallis rank sum test were used to test the statistical differences. The results showed that the number of patients with allergic rhinitis in 30 hospitals increased year by year from 2016 to 2019, with an increase of 97.9%. In 2020, the number of patients decreased. In 2021, the number of visits returned to the pre-epidemic level (461 332); The number of patients with allergic rhinitis was the highest in September, with a seasonal index of 177.6%, while the lowest number was in February, accounting for only 47.2%; a significant difference was observed in the number of patients in different age groups(H=45 319.48, P<0.05), and patients under 15 years old accounted for the highest proportion(819 284 visits); There were significant differences between patients of different genders in the 45-59 year old group (t=-4.26, P<0.05).There were relatively more patients with allergic rhinitis in Dongcheng District(31.1%) than in Huairou District and Miyun District (0.4%). In conclusion, since 2016, the number of patients increased significantly, with a varied trend in different seasons. Most patients were children. There were more patients in the central urban area than in the outer suburbs.
Subject(s)
Child , Humans , Female , Male , Adolescent , Middle Aged , Beijing/epidemiology , Big Data , Epidemics , Hospitals , Rhinitis, Allergic/epidemiologyABSTRACT
To explore the characteristics of big data of patients with allergic rhinitis, including the time, population and spatial distribution of allergic rhinitis in Beijing from 2016 to 2021, so as to provide reference for the prevention and treatment of this disease. Descriptive epidemiological methods were used to analyze the distribution (including gender, age and location)and trend of allergic rhinitis patients in 30 pilot hospitals from January 2016 to December 2021, T test and Kruskal-Wallis rank sum test were used to test the statistical differences. The results showed that the number of patients with allergic rhinitis in 30 hospitals increased year by year from 2016 to 2019, with an increase of 97.9%. In 2020, the number of patients decreased. In 2021, the number of visits returned to the pre-epidemic level (461 332); The number of patients with allergic rhinitis was the highest in September, with a seasonal index of 177.6%, while the lowest number was in February, accounting for only 47.2%; a significant difference was observed in the number of patients in different age groups(H=45 319.48, P<0.05), and patients under 15 years old accounted for the highest proportion(819 284 visits); There were significant differences between patients of different genders in the 45-59 year old group (t=-4.26, P<0.05).There were relatively more patients with allergic rhinitis in Dongcheng District(31.1%) than in Huairou District and Miyun District (0.4%). In conclusion, since 2016, the number of patients increased significantly, with a varied trend in different seasons. Most patients were children. There were more patients in the central urban area than in the outer suburbs.
Subject(s)
Child , Humans , Female , Male , Adolescent , Middle Aged , Beijing/epidemiology , Big Data , Epidemics , Hospitals , Rhinitis, Allergic/epidemiologyABSTRACT
Objective:To analyze influencing factors of coronary heart disease(CHD)in advanced aged population and the therapeutic effect of percutaneous coronary intervention(PCI).Methods:According to diagnosed as CHD or not,a total of 209 aged patients underwent cardio-and cerebrovascular examination in our hospital were divided into CHD group(n=104)and no CHD group(n=105),and general clinical data were compared between two groups.According to treatment method,CHD group was divided into routine treatment group(received routine medication)and PCI group;and recovery time,hospital stay,incidence rate of adverse events during admission and prognosis within one-year follow-up were compared between two groups.Influencing factors of CHD in aged population was analyzed.Results:Compared with no CHD group,there were significant rise in percentages of age>80 years,smoking,diabetes mellitus,hypertension,total cholesterol>5.17mmol/L,triglyceride>1.7mmol/L,high density lipoprotein cholesterol(HDL-C)<0.96mmol/L,low density lipoprotein cholesterol>3.37mmol/L,uric acid>420μmol/L and fibrinogen>4 g/L in CHD group(P<0.05 or<0.01).Compared with routine treat-ment group,there were significant reductions in recovery time,hospital stay,incidence rates of adverse events,lu-men loss/restenosis,primary and secondary endpoint events within one-year follow-up in PCI group(P<0.05 or<0.01).Binary Logistic regression analysis indicated that age>80 years,uric acid>420μmol/L and HDL-C<0.96mmol/L were independent risk factors for CHD in advanced aged population(OR=1.755~6.103,P<0.05 or<0.01).Conclusion:Age>80 years,uric acid>420μmol/L and HDL-C<0.96 mmol/L are independent risk fac-tors for coronary heart disease in advanced aged population.PCI can significantly shorten recovery time and treat-ment time in advanced aged patients with coronary heart disease with good safety.
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To discuss the effect of varicella vaccination on the clinical characteristics of herpes zoster (shingles) cases aged 20 years and under, and analyze its clinical features. Based on the Yichang Health Big Data Platform, a descriptive study was conducted to collect the information of cases aged 20 years and under in three medical institutions of Yichang Central People's Hospital, Yichang First People's Hospital and Yichang Second People's Hospital from March 2019 to September 2020. According to the history of varicella vaccine, cases were divided into vaccination group and non-vaccination group, and their clinical features and outcomes were compared. The results showed that 46 shingles cases, aged from 7 to 20 years old, were included in this study. 26 males (56.5%), 20 females (43.5%), 15 cases in vaccination group (32.6%) and 31 cases in non-vaccination group (67.4%). 28 cases had thoracic involvement, followed by lumbar (n=8), cranial (n=7) involvements and extremities (n=7). The spread of herpes skin area: 2 cases involved too large area, 21 cases of 10 cm×10 cm, 14 cases of 5 cm×5 cm, 9 cases of 1 cm×1 cm. Herpes number: 26 cases had 10-49 herpes, followed by <10 herpes (n=9), uncountable herpes (n=7) and 50-99 herpes (n=4). The clinical course[M(Q1,Q3)] lasted 20.5 (13.5,24.8) d averagely, 5 cases had postherpetic neuralgia (PHN) and 1 case had respiratory complications. Shingles decrustation time was significantly shorter in vaccination group (Z=-2.01, P<0.05), and there was no significant difference in other characteristics by vaccination. In conclusion, the number and spread of shingles in most children and adolescents are less, and the complications such as PHN are less. Varicella vaccination can reduce the decrustation time and relieve shingles cases with some clinical symptoms.
Subject(s)
Adolescent , Child , Female , Humans , Male , Young Adult , Chickenpox/prevention & control , Herpes Zoster/prevention & control , Herpes Zoster Vaccine/therapeutic use , Herpesvirus 3, Human , Neuralgia, Postherpetic/prevention & controlABSTRACT
Objective: To analyze the genetic characteristics of varicella-zoster virus (VZV) in people aged 20 years and under in Yichang City of Hubei Province from 2019 to 2020. Methods: Based on the Yichang Health Big Data Platform, we investigated cases 20 and under clinically diagnosed as herpes zoster in three hospitals from March 2019 to September 2020. Collecting vesicle fluid and throat swab samples of the cases and completing questionnaires to obtain basic information. Real-time fluorescent quantitative PCR was used for positive identification of the virus. PCR amplification of VZV's open reading frame (ORF) and sequencing of the products to determine the VZV genotype. Analyze mutations at some specific single nucleotide polymorphism (SNP) sites. Results: Among 46 cases of herpes zoster, the male to female ratio was 1.3∶1 (26∶20) and the age ranged from 7 to 20 years old. Fifteen cases had been vaccinated against varicella, including 13 and 2 cases of 1 and 2 doses, respectively. VZV strains were detected in 34 samples (73.91%), all belonging to Clade 2. Phylogenetic tree analysis of the nucleotide of ORF22 showed, compared with Clade 2 referenced strains, the sequence matching degree of nucleotide for all 34 samples was 99.0% to 100.0%. Conclusion: The main VZV strain causing herpes zoster in people aged 20 years and under in Yichang from 2019 to 2020 was Clade 2.
Subject(s)
Humans , Child , Adolescent , Young Adult , Adult , Herpesvirus 3, Human/genetics , Phylogeny , Herpes Zoster/epidemiology , Polymorphism, Single Nucleotide , Real-Time Polymerase Chain Reaction , NucleotidesABSTRACT
BACKGROUND: Recent studies have demonstrated that mesenchymal stem cells (MSCs) can rescue injured target cells via mitochondrial transfer. However, it has not been fully understood how bone marrow-derived MSCs repair glomeruli in diabetic kidney disease (DKD). AIM: To explore the mitochondrial transfer involved in the rescue of injured glomerular endothelial cells (GECs) by MSCs, both in vitro and in vivo. METHODS: In vitro experiments were performed to investigate the effect of co-culture with MSCs on high glucose-induced GECs. The transfer of mitochondria was visua lized using fluorescent microscopy. GECs were freshly sorted and ultimately tested for apoptosis, viability, mRNA expression by real-time reverse transcri ptase-polymerase chain reaction, protein expression by western blot, and mitochondrial function. Moreover, streptozotocin-induced DKD rats were infused with MSCs, and renal function and oxidative stress were detected with an automatic biochemical analyzer and related-detection kits after 2 wk. Kidney histology was analyzed by hematoxylin and eosin, periodic acid-Schiff, and immunohistochemical staining. RESULTS: Fluorescence imaging confirmed that MSCs transferred mitochondria to injured GECs when co-cultured in vitro. We found that the apoptosis, proliferation, and mitochondrial function of injured GECs were improved following co-culture. Additionally, MSCs decreased pro-inflammatory cytokines [interleukin (IL)-6, IL-1ß, and tumor necrosis factor-α] and pro-apoptotic factors (caspase 3 and Bax). Mitochondrial transfer also enhanced the expression of superoxide dismutase 2, B cell lymphoma-2, glutathione peroxidase (GPx) 3, and mitofusin 2 and inhibited reactive oxygen species (ROS) and dynamin-related protein 1 expression. Furthermore, MSCs significantly ameliorated functional parameters (blood urea nitrogen and serum creatinine) and decreased the production of malondialdehyde, advanced glycation end products, and ROS, whereas they increased the levels of GPx and superoxide dismutase in vivo. In addition, significant reductions in the glomerular basement membrane and renal interstitial fibrosis were observed following MSC treatment. CONCLUSION: MSCs can rejuvenate damaged GECs via mitochondrial transfer. Additionally, the improvement of renal function and pathological changes in DKD by MSCs may be related to the mechanism of mitochondrial transfer.
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Antrodia camphorata (A. camphorata) is an edible fungus containing various bioactive compounds generally used for health benefits. This study aimed to explore the potential neuroprotective activities of solid-state-cultured mycelium of A. camphorata (SCMAC) against Parkinson's disease (PD), as well as the underlying mechanism using an in vitro 6-hydroxydopamine (6-OHDA)-induced PC12 cell model. The results showed that SCMAC extracts alleviated cell toxicity induced by 6-OHDA and the loss of dopaminergic neurons, which was confirmed by the increase of cell viabilities, inhibition of cell apoptosis, the upregulation of tyrosine hydroxylase (TH) and dopamine transporter (DAT) levels and the downregulation of α-Synuclein level. After purification, 11 compounds were identified by the NMR technique, including a quinone, four phenolic acid derivatives, three ubiquinone derivatives, two alkaloids, and a triterpenoid. The present study suggests that SCMAC could be an attractive candidate for the prevention or treatment of PD. PRACTICAL APPLICATIONS: Parkinson's disease seriously affects the lifetime and quality of the elder population for a long history. Long-term consumption of L-DOPA will result in side effects, such as developing abnormal involuntary movements called dyskinesia. This study showed that natural SCMAC extracts could be a potential therapeutic agent for the treatment of neurodegenerative disorder.
Subject(s)
Antrodia , Parkinson Disease , Animals , Antrodia/chemistry , Mycelium/chemistry , Oxidopamine/analysis , Oxidopamine/toxicity , PC12 Cells , Parkinson Disease/drug therapy , Polyporales , RatsABSTRACT
Four undescribed regular rosane-type diterpenoids euphominoids M-P and three undescribed rearranged rosane-type diterpenoids euphomilones C-E were isolated from the whole plants of Euphorbia milii Des Moul., along with nine known compounds. Their structures were elucidated by detailed interpretation of the NMR and mass spectroscopy. The absolute configurations were established by single-crystal X-ray diffraction experiments, as well as comparative analyses of calculated and experimental ECD spectra. Euphominoid M featured a highly oxygenated ring A and a rare four-membered oxygen ring while euphomilones C-E possessed 7/5/6 or 5/7/6 fused ring systems, which were rarely occurring in rosane-type diterpenoids. In the in-vitro bioassays, 19-norrosa-1,3,5(10),15-tetraene-2,3-diol and antiquorin showed more potent α-glucosidase inhibitory activity than the positive control acarbose while euphominoid C exhibited significant inhibitory activity against both α-glucosidase and ß-glucuronidase. To the best of our knowledge, it was the first time that rosane-type diterpenoids were reported as ß-glucuronidase inhibitors.
Subject(s)
Diterpenes , Euphorbia , Diterpenes/chemistry , Diterpenes/pharmacology , Enzyme Inhibitors , Euphorbia/chemistry , Glucuronidase , Molecular Structure , alpha-GlucosidasesABSTRACT
Chemical investigation into the stems of the medicinal plant Schisandra sphaerandra led to the isolation and identification of a new dibenzocyclooctadiene lignan sphaerandrin A (1) and 11 known ones gomisin B (2), schirubrisin B (3), kadsuphilin B (4), schizandrin (5), benzoylgomisin Q (6), angeloylgomisin Q (7), gomisin G (8), schisanwilsonin O (9), isogomisin O (10), schisantherin D (11), and wuweizisu C (12). The structure of the new compound was elucidated by comprehensive spectroscopic methods including 1 D/2D NMR, HRESIMS, and CD spectrometry. To the best of our knowledge, compounds 2 - 11 were obtained from this species for the first time. All the compounds were evaluated for the cytotoxic activity against the triple-negative breast cancer cell lines MDA-MB-231 and HCC-1937.
Subject(s)
Carcinoma, Hepatocellular , Lignans , Liver Neoplasms , Plants, Medicinal , Schisandra , Cyclooctanes , Humans , Lignans/pharmacology , Plant StemsABSTRACT
Objective: To analyze the clinical characteristics, treatment response, and prognosis of newly diagnosed symptomatic multiple myeloma (MM) patients with systemic light chain amyloidosis (AL) . Methods: The clinical data of 160 patients with newly diagnosed MM treated at the First Affiliated Hospital of Soochow University from January 1, 2017 to October 31, 2018, were retrospectively analyzed. According to the histopathological biopsy results of bone marrow, skin, and other tissues, the patients were divided into two groups according to whether amyloidosis was combined or not, namely, the MM+AL group and the MM group. The clinical characteristics and treatment responses of the two groups were compared. Results: Among the 160 patients with newly diagnosed MM, there were 42 cases in the MM+AL group and 118 cases in the MM group. In terms of clinical features, the involved light chain and non-involved light chain (dFLC) in the MM+AL group was significantly higher than that in the MM group (P=0.039) . After induction treatment, the MM+AL group had a higher overall response rate (85.7%vs 79.7%, P<0.05) and higher excellent partial response (76.2%vs 55.1%, P<0.05) . After a median follow-up of 26 (0.25-41) months, there was no significant difference in the progression free survival and overall survival (OS) between the two groups (P>0.05) . The OS of patients in autologous hematopoietic stem cell transplantation group was better than that in non transplantation group (P<0.05) .The prognosis of patients with cardiac involvement in the MM+AL group was significantly worse than that in the MM group and MM+AL group without cardiac involvement (P<0.001) , with a median OS of only 13 months. Conclusion: The differential diagnosis between the MM+AL and MM groups requires histopathology, particularly for patients with significantly increased dFLC. The overall remission rate of patients in MM+AL group after 4 courses of induction chemotherapy was higher than that in MM group. The prognosis of patients with cardiac involvement in MM+AL group was poor.
Subject(s)
Humans , Amyloidosis/diagnosis , Immunoglobulin Light Chains , Immunoglobulin Light-chain Amyloidosis/therapy , Multiple Myeloma/therapy , Prognosis , Retrospective StudiesABSTRACT
Fungal natural products are rich sources of clinical drugs. Particularly, the fungicolous fungi have a large number of biosynthetic gene clusters (BGCs) to produce numerous bioactive natural products, but most BGCs are silent in the laboratory. We have shown that a fungicolous fungus Calcarisporiumarbuscula NRRL 3705 predominantly produces the highly reduced polyketide-type mycotoxins aurovertins. Here after evaluation of the aurovertin-null mutant ΔaurA as an efficient host, we further screened two strong promoters aurBp and A07068p based on RNA-Seq, and successfully activated an endogenous gene cluster from C. arbuscula as well as three additional exogenous BGCs from other fungi to produce polyketide-type natural products. Thus, we showed an efficient expression system from the fungicolous fungus C. arbuscula, which will be highly beneficial and complementary to the conventional Aspergillus and Penicillium fungal cell factories, and provides a useful toolkit for genome-wide mining of bioactive natural products from fungicolous fungi.
Subject(s)
Biological Products/metabolism , Hypocreales/metabolism , Aspergillus/genetics , Hypocreales/genetics , Multigene Family/genetics , Multigene Family/physiology , Penicillium/geneticsABSTRACT
Chemical investigation into the culture broth of the plant endophyte Penicillium sp. HS-11 in the modified Martin's medium supplemented with subemylanilide hydroxamic acid (SAHA), a well-known histone deacetylase (HDACs) inhibitor, led to the isolation and identification of two induced products 4-epipenicillone B (1) and (R)-(+)-chrysogine (2). 4-epipenicillone B (1) was obtained as a new compound whose structure was elucidated by comprehensive spectroscopic methods including 1 D/2D NMR, HRESMS, and quantum chemistry calculations including DFT GIAO 13C NMR and ECD calculation. Acquisition of 4-epipenicillone B (1) enriched the chemical diversities of fungal natural products possessing a tricyclo [5.3.1.03,8] undecane skeleton. The cytotoxic activity of 1 was also evaluated.
Subject(s)
Penicillium , Polyketides , Epigenesis, Genetic , Epigenomics , Penicillium/chemistry , Penicillium/isolation & purification , Polyketides/chemistry , Polyketides/pharmacologyABSTRACT
Microeunicellols A (1) and B (2), two undescribed eunicellin diterpenoids, were isolated from the culture of a bacterial symbiont, Streptomyces albogriseolus SY67903. Their structures, including absolute configurations revealed by spectroscopic data and single-crystal X-ray diffraction analysis, are closely related with the diterpenoids from its host, a South China Sea gorgonian, Muricella sibogae. This is the first report of eunicellin diterpenoids, commonly coral-derived, from a bacterial symbiont of coral. The chemical metabolic relationship between the bacterium and its host is discussed. Biological evaluation revealed that compound 1 possessed cytotoxicities against several human cancer cell lines.
Subject(s)
Diterpenes/pharmacology , Streptomyces/chemistry , Terpenes/pharmacology , Animals , Anthozoa/chemistry , Cell Line, Tumor , China , Diterpenes/chemistry , Diterpenes/isolation & purification , Humans , Magnetic Resonance Spectroscopy , Molecular Structure , Terpenes/isolation & purificationABSTRACT
α-Mangostin (α-M) is a natural xanthone from the pericarp of fruit Garcinia mangostana and possesses versatile biological activities. α-M has a therapeutic potential to treat Alzheimer's disease (AD) because of its anti-inflammatory, antioxidative, and neuroprotective activities. However, the use of α-M for AD treatment is limited due to its cytotoxic activities and relatively low potency. Modifications of its chemical structure were needed to reduce its cytotoxicity and improve its therapeutic potential against AD. For this purpose, 16 α-M carbamate derivatives were synthesized. An animal model of AD was established, and the effects of AMG-1 on the spatial learning ability and memory ability were evaluated using behavioral tests. The effect on neuropathology was tested by histopathological evaluation, Nissl staining, and silver staining. Computational systems pharmacology analysis using the chemogenomics knowledgebase was applied for network studies. Compound-target, target-pathway, and target-disease networks were constructed, integrating both in silico analysis and reported experimental data. The results show that AMG-1 can demonstrate its therapeutic effects in a one-molecule, multiple-targets manner to remarkably ameliorate neurological changes and reverse behavioral deficits in AD model rats. The improved cognitive function and alleviated neuronal injury can be observed. The ability of AMG-1 to scavenge ß-amyloid in the hippocampus was validated in AD model rats.
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Spiroinonotsuoxotriols A (1) and B (2), two highly rearranged pentacyclic triterpenoids featuring a novel 7(8 â 9)abeo-21,24-cyclo-lanostane skeleton, together with their proposed precursors 3-5, were isolated from the sclerotia of the white-rot fungus Inonotus obliquus. Their structures including the absolute configurations were elucidated by extensive spectroscopic analyses and single-crystal X-ray diffraction. The biogenetic pathway of 1 and 2 was proposed. Compounds 1 and 2 exhibited potent α-glucosidase inhibitory activity as compared with the positive control acarbose.
Subject(s)
Basidiomycota , Triterpenes , Basidiomycota/chemistry , Inonotus , Molecular Structure , Triterpenes/chemistryABSTRACT
The biotransformation of huperzine A (hupA), one of the characteristic bioactive constituents of the medicinal plant Huperzia serrata, by a fungal endophyte of the host plant was studied. Two previously undescribed compounds 1-2, along with a known analog 8α,15α-epoxyhuperzine A (3), were isolated and identified. The structures of all the isolates were established by spectroscopic methods including NMR, MS, IR, and UV spectra. In particular, the absolute configurations of 1 and 2 were elucidated by CD spectra comparison and theoretic NOE strength calculation. In the LPS-induced neuro-inflammation injury assay, 1-3 exhibited moderate neuroprotective activity by increasing the viability of U251 cell lines with EC50 values of 35.3⯱â¯0.9, 32.1⯱â¯0.9, and 50.3⯱â¯0.8â¯nM, respectively.
Subject(s)
Alkaloids/metabolism , Huperzia/microbiology , Polyporales/metabolism , Sesquiterpenes/metabolism , Biotransformation , Cell Line, Tumor , China , Endophytes/metabolism , Humans , Huperzia/chemistry , Neuroprotective Agents , Phytochemicals/metabolism , Plants, Medicinal/chemistry , Plants, Medicinal/microbiologyABSTRACT
The biotransformation of huperzine B (hupB), one of the characteristic bioactive constituents of the medicinal plant Huperzia serrata, by a fungal endophyte of the host plant was studied. One new compound, 8α,15α-epoxyhuperzine B (1), along with two known oxygenated hupB analogs, 16-hydroxyhuperzine B (2) and carinatumin B (3), was isolated and identified. The structures of all the isolates were deduced by spectroscopic methods including NMR, MS, IR, and UV spectra. The known compounds 2 and 3 were obtained from a microbial source for the first time. To the best of our knowledge, it is the first report on the microbial transformation of hupB and would facilitate further structural modification of hupB by chemo-enzymatic method. In the LPS-induced neuro-inflammation injury assay, 8α,15α-epoxyhuperzine B (1) exhibited moderate neuroprotective activity by increasing the viability of U251 cell lines with an EC50 of 40.1â nm.
Subject(s)
Alkaloids/chemistry , Huperzia/chemistry , Alkaloids/metabolism , Alkaloids/pharmacology , Biotransformation , Cell Line , Cell Survival/drug effects , Humans , Huperzia/metabolism , Lipopolysaccharides/toxicity , Molecular Conformation , Neurons/cytology , Neurons/drug effects , Neurons/metabolism , Plants, Medicinal/chemistry , Plants, Medicinal/metabolism , Protective Agents/chemistry , Protective Agents/pharmacologyABSTRACT
OBJECTIVE@#Apios americana, a plant used as a staple ingredient of native American diets, has various properties, including anti-cancer, anti-hyperglycemic, hypotensive, and anti-inflammatory activity. In Japan, Apios is used as a post-natal medication. After parturition, women undergo a period of recovery as they return to pre-pregnancy conditions. However, few health products that aid post-partum recovery are on the market. We explored whether Apios can accelerate the post-partum recovery process, in particular the involution of the uterus.@*METHODS@#Female rats kept in individual cages were mated with two male rats, with the exception of the control group (female rats without mating, on basal diet; n=6). After delivery, rats were divided into five groups based on their diet: basal diet (model; n=6); basal diet+oral intake at 5.4 g/kg of Chanfukang granules (a Chinese patent medicine preparation for post-partum lochia) (positive; n=6); basal diet containing 10% Apios powder (low; n=6); basal diet containing 20% Apios powder (medium; n=6); basal diet containing 40% Apios powder (high; n=6). Five days later, uteri and spleens were weighed. Uterus and spleen indices for each rat were calculated by dividing visceral weight by the total weight. Hormone and cytokine concentrations were measured using enzyme-linked immunosorbent assay (ELISA). Histological analysis of uteri was completed using hematoxylin and eosin (H&E) staining. Expression of matrix metalloproteinases and inhibitors in uteri was measured by western blotting.@*RESULTS@#Our results showed that Apios treatment reduced the post-partum uterus index and regulated the hormone concentrations. Moreover, we found that the process of uterine involution was accelerated, based on morphological changes in the uterus. In addition, our results indicated that Apios alleviated the inflammatory response induced by the involution process. Transforming growth factor β was also found to be regulated by Apios. There were significant downregulation of matrix metalloproteinases and upregulation of their inhibitors by Apios, which suggested that Apios increased the rate of the collagen clearance process.@*CONCLUSIONS@#These results, based on experimental observations at the molecular and protein levels, verified our hypothesis that Apios can improve uterine involution, and demonstrated the potential application of Apios in post-partum care.