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1.
Diabetes Metab Syndr ; 18(1): 102936, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38171152

RESUMO

OBJECTIVE: To incorporate new clusters in the MARCH (Metformin and AcaRbose in Chinese patients as the initial Hypoglycemic treatment) cohort of newly diagnosed type 2 diabetes (T2D) patients and compare the anti-glycemic effects of metformin and acarbose across different clusters. METHODS: K-means cluster analysis was performed based on six clinical indicators. The diabetic clusters in the MARCH cohort were retrospectively associated with the response to metformin and acarbose. RESULTS: A total of 590 newly diagnosed T2D patients were classified by data-driven clusters into the MARD (mild obesity-related diabetes) (34.1 %), MOD (mild obesity-related diabetes) (34.1 %), SIDD (severe insulin-deficient diabetes) (20.3 %) and SIRD (severe insulin-resistant diabetes) (11.5 %) subgroups at baseline. At 24 and 48 weeks, 346 participants had finished the follow-up. After the adjustment of age, gender, weight, baseline HbA1c, baseline fasting glucose and 2-h postprandial blood glucose (2hPG), metformin mainly decreased the fasting glucose (0.07 ± 0.89 vs -0.26 ± 0.83, P = 0.043) in the MARD subgroup presented with OGTT (oral glucose tolerance test) results compared with acarbose group at 24 weeks. Acarbose led to a greater decrease in 2hPG in the MOD subgroup compared with metformin group (0.08 ± 0.86 vs -0.24 ± 0.92, P = 0.037) at 24 weeks. There was a also significant interaction between cluster and treatment efficacy in HbA1c (glycated hemoglobin) reduction in metformin and acarbose groups at 24 and 48 weeks (pinteraction<0.001). CONCLUSIONS: Metformin and acarbose affected different metabolic variables depending on the diabetes subtype.


Assuntos
Diabetes Mellitus Tipo 2 , Metformina , Humanos , Acarbose/uso terapêutico , Hemoglobinas Glicadas , Estudos Retrospectivos , Hipoglicemiantes/uso terapêutico , Metformina/uso terapêutico , Glicemia/metabolismo , Insulina , Obesidade/tratamento farmacológico
3.
J Nanobiotechnology ; 21(1): 489, 2023 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-38111035

RESUMO

Orthotopic advanced hepatic tumor resection without precise location and preoperative downstaging may cause clinical postoperative recurrence and metastasis. Early accurate monitoring and tumor size reduction based on the multifunctional diagnostic-therapeutic integration platform could improve real-time imaging-guided resection efficacy. Here, a Near-Infrared II/Photoacoustic Imaging/Magnetic Resonance Imaging (NIR-II/PAI/MRI) organic nanoplatform IRFEP-FA-DOTA-Gd (IFDG) is developed for integrated diagnosis and treatment of orthotopic hepatic tumor. The IFDG is designed rationally based on the core "S-D-A-D-S" NIR-II probe IRFEP modified with folic acid (FA) for active tumor targeting and Gd-DOTA agent for MR imaging. The IFDG exhibits several advantages, including efficient tumor tissue accumulation, good tumor margin imaging effect, and excellent photothermal conversion effect. Therefore, the IFDG could realize accurate long-term monitoring and photothermal therapy non-invasively of the hepatic tumor to reduce its size. Next, the complete resection of the hepatic tumor in situ lesions could be realized by the intraoperative real-time NIR-II imaging guidance. Notably, the preoperative downstaging strategy is confirmed to lower the postoperative recurrence rate of the liver cancer patients under middle and advanced stage effectively with fewer side effects. Overall, the designed nanoplatform demonstrates great potential as a diagnostic-therapeutic integration platform for precise imaging-guided surgical navigation of orthotopic hepatic tumors with a low recurrence rate after surgery, providing a paradigm for diagnosing and treating the advanced tumors in the future clinical translation application.


Assuntos
Neoplasias Hepáticas , Nanopartículas , Cirurgia Assistida por Computador , Humanos , Fototerapia , Imageamento por Ressonância Magnética/métodos , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/cirurgia , Linhagem Celular Tumoral
4.
World J Clin Cases ; 11(26): 6213-6222, 2023 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-37731555

RESUMO

BACKGROUND: Aggressive variant prostate cancer (AVPC) is a rare disease that progresses rapidly. The first-line treatment for AVPC is currently unknown. We examined a rare case of AVPC with rare brain and bladder metastases. A summary review of the mechanism of development, clinicopathological manifestations, associated treatments and prognosis of this disease is presented. CASE SUMMARY: The patient was diagnosed with prostate cancer (PCA), and was actively treated with endocrine therapy, radiotherapy, chemotherapy, and traditional Chinese medicine. Unfortunately, he was insensitive to treatment, and the disease progressed rapidly. He died five years after being diagnosed with PCA. CONCLUSION: We should reach consensus definitions of the AVPC and other androgen receptor-independent subtypes of PCA and develop new biomarkers to identify groups of high-risk variants. It is crucial to complete a puncture biopsy of the tumor or metastatic lesion as soon as possible in patients with advanced PCA who exhibit clinical features such as low Prostate-specific antigen levels, high carcinoembryonic antigen levels, and insensitivity to hormones to determine the pathological histological type and to create a more aggressive monitoring and treatment regimens.

5.
BMC Med ; 21(1): 292, 2023 08 07.
Artigo em Inglês | MEDLINE | ID: mdl-37545008

RESUMO

BACKGROUND: Folic acid (FA) supplementation is associated with a lower risk of the neural tube and heart defects and is recommended for women of childbearing age. Although there are detailed recommendations, differences in the initiation time and duration of FA supplementation remain poorly studied. METHODS: A multicentre prospective study of 17,713 women was conducted. The incidence of congenital malformations in women taking a recommended dosage (e.g. 0.4 or 0.8 mg/day) of FA was compared with that in women without supplementation. The predicted probability of malformations by the initiation time and duration of FA use was estimated to determine optimal options. RESULTS: Periconceptional FA supplementation was associated with a lower and insignificant risk of congenital malformations (1.59% vs. 2.37%; odds ratio [OR] 0.69; 95% confidence interval [CI]: 0.44-1.08), heart defects (3.8 vs. 8.0 per 1000 infants; OR, 0.47; 0.21-1.02), and neural tube defects (7.0 vs. 11.5 per 10,000 infants; OR, 0.64; 0.08-5.15). FA use after pregnancy provided greater protection against total malformations. Statistically significant associations were found in women who initiated FA supplementation in the first month of gestation (OR, 0.55; 95% CI: 0.33-0.91) and in those who supplemented for 1 to 2 months (OR, 0.59; 95% CI: 0.36-0.98). Similar results were found for heart defects. The optimal initiation time was 1.5 (optimal range: 1.1 to 1.9) months before pregnancy and a duration of 4.0 (3.7 to 4.4) months was reasonable to achieve the lowest risk of congenital malformations. Heart defect prevention required an earlier initiation (2.2 vs. 1.1 months before pregnancy) and a longer duration (4.7 vs. 3.7 months) than the prevention of other malformations. CONCLUSIONS: The timely initiation of FA supplementation for gestation was associated with a decreased risk of congenital malformations, which was mainly attributed to its protection against heart defects. The initiation of FA supplementation 1.5 months before conception with a duration of 4 months is the preferred option for congenital malformation prevention. TRIAL REGISTRATION: Chictr.org.cn identifier: ChiCTR-SOC-17010976.


Assuntos
Ácido Fólico , Complexo Vitamínico B , Gravidez , Lactente , Feminino , Humanos , Cuidado Pré-Concepcional , Estudos Prospectivos , Suplementos Nutricionais
6.
Acta Obstet Gynecol Scand ; 102(6): 735-743, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37073619

RESUMO

INTRODUCTION: The potential teratogenic risk of traditional Chinese medicine (TCM) is of widespread concern; however, related evidence is largely absent in humans. This study aimed to compare the prevalence of congenital malformations between pregnant women with and without TCM exposure. MATERIAL AND METHODS: This was a multicenter prospective cohort study of 17 713 women who participated in a survey on periconceptional TCM exposure. Primary outcome was congenital malformations diagnosed from a survey conducted on the day 42 after delivery. RESULTS: A total of 16 751 pregnant women with 273 congenital malformations were included in the analysis. Fetuses exposed to TCM had an increased risk of congenital malformations compared to those without exposure (odds ratio [OR] 2.10; 95% confidence interval [CI] 1.09-4.02) after controlling for potential confounders. There were significant associations with congenital malformations in women with early pregnant exposure (OR 2.04, 95% CI 1.00-4.20) and for those who received ≥2 TCM formulas (OR 5.84, 95% CI 1.44-23.65). Pre-pregnancy TCM exposure was significantly associated with an increased risk of congenital heart defects (OR 12.69; 95% CI 3.01-53.51). CONCLUSIONS: Periconceptional TCM exposure is associated with an increased risk of congenital malformation. This effect was cumulative and sensitive to periconceptional age. Therefore, TCM deserves more attention and should be used cautiously for pregnant women and those trying to become pregnant.


Assuntos
Anormalidades Induzidas por Medicamentos , Anormalidades Congênitas , Cardiopatias Congênitas , Complicações na Gravidez , Feminino , Gravidez , Humanos , Estudos Prospectivos , Medicina Tradicional Chinesa/efeitos adversos , Cardiopatias Congênitas/epidemiologia , Cardiopatias Congênitas/complicações , Exposição Materna/efeitos adversos , Anormalidades Induzidas por Medicamentos/epidemiologia , Anormalidades Induzidas por Medicamentos/etiologia , Anormalidades Congênitas/epidemiologia , Anormalidades Congênitas/etiologia
7.
Artigo em Inglês | MEDLINE | ID: mdl-36193124

RESUMO

Objective: To explore the effect of bisphosphonates after vertebroplasty in patients with osteoporotic vertebral compression fractures (OVCF), and to analyze the relationship between the use of bisphosphonates and vertebral refracture. Methods: A total of 150 patients with OVCF were selected from the pain department of our hospital from January 2018 to May 2020. All patients received vertebroplasty after admission, and were divided into the surgery group (62 cases) and combined with the bisphosphonates group (combined group, 88 cases) according to whether patients had used bisphosphonates after surgery. Before surgery, 1 month, 3 months, 6 months, and 1 year after surgery, visual analogue scale (VAS), Oswestry disability index (ODI), vertebral body and femoral neck bone mineral density (BMD), and Cobb Angle were collected, and the differences among groups were compared to analyze the treatment effect. After the follow-up, patients were divided into two groups according to whether vertebral refracture occurred during the follow-up period. Clinical characteristics, general information, and surgical indicators of patients in the two groups were collected, and related factors of postoperative vertebral refracture were analyzed. Results: There were no significant differences in preoperative VAS score, ODI index, BMD value, and Cobb angle between the two groups (P > 0.05). At 12 months after surgery, VAS score, ODI index, and Cobb angle decreased, while BMD value increased in both groups. The VAS score, ODI index, and Cobb angle in the combined group were lower than those in the operation group, while the BMD value was higher than that in the operation group, and the difference was significant (P < 0.05). The results of multivariate regression analysis showed that in BMD, no postoperative antiosteoporosis treatment, bone cement leakage, and poor cement diffusion were independent risk factors for vertebral refracture after vertebroplasty in patients with vertebral compression fractures. Conclusion: In order to avoid recurrent fractures in OVCF patients, attention should be paid to BMD, whether patients take antiosteoporosis drugs, whether bone cement permeation occurs and the diffusion of bone cement, etc. The above factors are the main influencing factors leading to recurrent fractures after PKP and PVP in the clinic.

8.
Zhongguo Zhong Yao Za Zhi ; 47(18): 4863-4876, 2022 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-36164896

RESUMO

Steroidal saponins, important natural organic compounds in Paris polyphylla var. yunnanensis, have good biological activity. Structural modification of steroidal saponins by microbial transformation could produce a large number of products with novel structures and excellent bioactivity, which can provide functional compounds for the research and development of steroidal drugs. This study summarized the research progress in steroidal saponins and their microbial transformation in P. polyphylla var. yunnanensis. P. polyphylla var. yunnanensis contains 112 steroidal saponins, 8 of which are used as substrates in 35 transformation reactions by 25 microbial species, with the highest transformation rate of 95%. Diosgenin is the most frequently used substrate. Furthermore, the strains, culture medium, reaction conditions, transformation rate, transformation reaction characteristics, and biological activities of the transformed products were summarized. This review may provide reference for the further research on microbial transformation of steroidal saponins in P. polyphylla var. yunnanensis.


Assuntos
Diosgenina , Liliaceae , Melanthiaceae , Saponinas , Diosgenina/análise , Liliaceae/química , Melanthiaceae/química , Rizoma/química , Saponinas/análise
9.
Medicine (Baltimore) ; 100(47): e27935, 2021 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-34964770

RESUMO

BACKGROUND: Primary dysmenorrhea (PD) occurs most often in adolescent girls. Tuina, a kind of Chinese massage, can effectively relieve women's pain and is widely used in clinical practice. However, there is no relevant systematic review show its effectiveness and safety. The study aims to assess the effectiveness and safety of Tuina for PD. METHODS: The following electronic databases will be searched from the respective dates of database inception to September 1st, 2021: The Cochrane Library, Web of Science, EMBASE, Springer, MEDLINE, China National Knowledge Infrastructure, the Chinese Biomedical Literature Database, the World Health Organization International Clinical Trials Registry Platform, the Chinese Scientific Journal Database, Wanfang database, and other sources. RESULTS: This study will provide a high quality comprehensive and/or descriptive analysis of existing evidence on Tuina therapy for PD. CONCLUSION: This study will provide the evidence of whether Tuina is an effective and safe intervention for women with PD. PROSPERO REGISTRATION NUMBER: CRD42021257392.


Assuntos
Dismenorreia/terapia , Medicina Tradicional Chinesa/métodos , Adolescente , Feminino , Humanos , Massagem , Metanálise como Assunto , Projetos de Pesquisa , Revisões Sistemáticas como Assunto
10.
Artigo em Inglês | MEDLINE | ID: mdl-34925530

RESUMO

Sishen Pill (SSP) is a classical prescription of traditional Chinese medicine and often used to treat gastrointestinal diseases, including ulcerative colitis (UC). However, its mechanism is still unclear. We aimed to determine the mechanism of SSP in the treatment of UC by investigating if it maintains the integrity of the intestinal mucosal barrier via the Rho A/Rho kinase (ROCK) signaling pathway. Administration of 2,4,6-trinitrobenzene sulfonic acid (TNBS) successfully induced chronic UC in rats, while the treatment effect of SSP was evaluated by body weight change, colonic length, colonic weight, colonic weight index, histological injury score, and pathological injury score after colitis rats were treated for 7 days. TNF-α and IL-1ß levels were analyzed by ELISA, and the proteins of PI3K/Akt and RhoA/ROCK signaling pathway and junction proteins expression were measured by western blotting assay, and the distribution of Claudin 5 was shown by immunofluorescence. SSP significantly improved the clinical symptoms of colitis in rats and reduced the expression of p-RhoA, ROCK1, PI3K, and Akt in the colon mucosa, while it increased the expression of p-Rac and related proteins (Claudin-5, JAM1, VE-cadherin, and Connexin 43). In addition, SSP increased p-AMPKα and PTEN proteins expression, decreased Notch1 level, and hinted that activation of the PI3K/Akt signaling pathway was inhibited. In conclusion, SSP effectively treated chronic colitis induced by TNBS, which may have been achieved by inhibiting PI3K/Akt signal to suppress activation of the Rho/ROCK signaling pathway to finally maintain the integrity of the intestinal mucosal barrier.

11.
Medicine (Baltimore) ; 100(24): e26366, 2021 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-34128892

RESUMO

BACKGROUND: The study aims to evaluate the effectiveness and safety of Baduanjin exercise for rehabilitation after COVID-19. METHODS: The following electronic databases will be searched from establishment to Jan 2021: Cochrane Library, MEDLINE, EMBASE, Web of Science, Springer, World Health Organization International Clinical Trials Registry Platform, China National Knowledge Infrastructure, Wan-fang database, Chinese Scientific Journal Database, Chinese Biomedical Literature Databases, and other databases, All published randomized controlled trials about this topic will be included. Two independent researchers will operate article retrieval, duplication removing, screening, quality evaluation, and data analyses by Review Manager (V.5.3.5). Meta-analyses, subgroup analysis, and/or descriptive analysis will be performed based on the included data conditions. RESULTS: The results of this study will provide a combination of high-quality evidence for researchers in the current field of COVID-19 treatment and rehabilitation. CONCLUSION: The conclusion of this study will provide the evidence of whether Baduanjin is an effective and safe intervention for rehabilitation after COVID-19. PROSPERO REGISTRATION NUMBER: CRD42020181078.


Assuntos
COVID-19/psicologia , COVID-19/reabilitação , Metanálise como Assunto , Qigong , Revisões Sistemáticas como Assunto , Protocolos Clínicos , Humanos , Qigong/efeitos adversos , SARS-CoV-2
12.
Plant Biotechnol J ; 19(7): 1412-1428, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33539631

RESUMO

Artemisinin, a sesquiterpene lactone widely used in malaria treatment, was discovered in the medicinal plant Artemisia annua. The biosynthesis of artemisinin is efficiently regulated by jasmonate (JA) and abscisic acid (ABA) via regulatory factors. However, the mechanisms linking JA and ABA signalling with artemisinin biosynthesis through an associated regulatory network of downstream transcription factors (TFs) remain enigmatic. Here we report AaTCP15, a JA and ABA dual-responsive teosinte branched1/cycloidea/proliferating (TCP) TF, which is essential for JA and ABA-induced artemisinin biosynthesis by directly binding to and activating the promoters of DBR2 and ALDH1, two genes encoding enzymes for artemisinin biosynthesis. Furthermore, AaORA, another positive regulator of artemisinin biosynthesis responds to JA and ABA, interacts with and enhances the transactivation activity of AaTCP15 and simultaneously activates AaTCP15 transcripts. Hence, they form an AaORA-AaTCP15 module to synergistically activate DBR2, a crucial gene for artemisinin biosynthesis. More importantly, AaTCP15 expression is activated by the multiple reported JA and ABA-responsive TFs that promote artemisinin biosynthesis. Among them, AaGSW1 acts at the nexus of JA and ABA signalling to activate the artemisinin biosynthetic pathway and directly binds to and activates the AaTCP15 promoter apart from the AaORA promoter, which further facilitates formation of the AaGSW1-AaTCP15/AaORA regulatory module to integrate JA and ABA-mediated artemisinin biosynthesis. Our results establish a multilayer regulatory network of the AaGSW1-AaTCP15/AaORA module to regulate artemisinin biosynthesis through JA and ABA signalling, and provide an interesting avenue for future research exploring the special transcriptional regulation module of TCP genes associated with specialized metabolites in plants.


Assuntos
Artemisia annua , Artemisininas , Ácido Abscísico , Artemisia annua/genética , Artemisininas/metabolismo , Ciclopentanos , Regulação da Expressão Gênica de Plantas , Oxilipinas , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo
13.
Zhongguo Zhong Yao Za Zhi ; 46(24): 6343-6352, 2021 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-34994126

RESUMO

This paper reviewed the traditional use of Paris polyphylla and its active components, aiming to provide reference for the development and utilization of this plant. It was found that P. polyphylla has been used as a medicinal plant by eight ethnic minorities. A total of 62 experiential effective recipes, including 29 simple recipes and 33 compound recipes, were analyzed for their indications, traditional processing methods, medicinal compatibilities, and administration doses. The top three in the eight ethnic minorities sorted by the quantity of folk recipes were the Yi nationality(18), Naxi nationality(13) and Bai nationality(12). P. polyphylla has been widely employed for the treatment of nine categories of diseases, especially the dermatologic diseases, trauma, and toxicosis currently. The collating of material basis for its traditional functions revealed 26 active components, among which 19 were steroidal saponins capable of resisting cancer, furuncles, carbuncles, abscesses, bacteria, inflammation and stopping bleeding. This study preliminarily proved the efficacy of P. polyphylla in treating cancer and respiratory system, digestive system, and genitourinary system diseases, which has provided clues for related basic research of P. polyphylla and development of new preparations.


Assuntos
Liliaceae , Melanthiaceae , Plantas Medicinais , Saponinas , Minorias Étnicas e Raciais
14.
Front Plant Sci ; 11: 563237, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33193491

RESUMO

Gastrodia elata, also named Tianma, is a valuable traditional Chinese herbal medicine. It has numerous important pharmacological roles such as in sedation and lowering blood pressure and as anticonvulsant and anti-aging, and it also has effects on the immune and cardiovascular systems. The whole genome sequencing of G. elata has been completed in recent years, which provides a strong support for the construction of the G. elata gene functional analysis platform. Therefore, in our research, we collected and processed 39 transcriptome data of G. elata and constructed the G. elata gene co-expression networks, then we identified functional modules by the weighted correlation network analysis (WGCNA) package. Furthermore, gene families of G. elata were identified by tools including HMMER, iTAK, PfamScan, and InParanoid. Finally, we constructed a gene functional analysis platform for G. elata . In our platform, we introduced functional analysis tools such as BLAST, gene set enrichment analysis (GSEA), and cis-elements (motif) enrichment analysis tool. In addition, we analyzed the co-expression relationship of genes which might participate in the biosynthesis of gastrodin and predicted 19 mannose-binding lectin antifungal proteins of G. elata. We also introduced the usage of the G. elata gene function analysis platform (GelFAP) by analyzing CYP51G1 and GFAP4 genes. Our platform GelFAP may help researchers to explore the gene function of G. elata and make novel discoveries about key genes involved in the biological processes of gastrodin.

16.
Zhongguo Zhong Yao Za Zhi ; 44(17): 3738-3744, 2019 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-31602947

RESUMO

Seventeen compounds were isolated from the 95% ethanol extract of the stems and leaves of Sapium discolor by using various chromatographic techniques,including silica gel,Sephadex LH-20,MCI,ODS,and semi-preparative HPLC. Their structures were elucidated as sapiumin F( 1),kadsulignan C( 2),ciwujiatone( 3),ethylbrevifolin carboxylate( 4),7-hydroxy-8-methoxycoumarin( 5),fraxetin( 6),fraxidin( 7),isofraxidin( 8),6,7,8-trimethoxycoumarin( 9),5,6,7,8-tetramethoxycoumarin( 10),8-hydroxy-5,6,7-trimethoxycoumarin( 11),3,3'-di-O-methylellagic acid( 12),3,3',4'-tri-O-methylellagic acid( 13),3'-methoxyellagic acid 4'-O-α-rhamnopyranoside( 14),4,5-didehydro-chebulic acid triethyl ester( 15),ent-kaurane-3-oxo-16α,17-diol( 16),and abscisic acid( 17) by spectroscopic data. Compound 1 is a new compound. Except for compounds 4,11,and 13,the remaining compounds were isolated from this plant for the first time. All the isolates were evaluated for their in vitro antineuroinflammatory activities,and the results showed that compounds 6 and 15 significantly inhibited nitric oxide production in lipopolysaccharide-induced BV-2 microglial cells,with IC50 values of 6. 06 and 6. 05 µmol·L-1,respectively.


Assuntos
Compostos Fitoquímicos/análise , Folhas de Planta/química , Caules de Planta/química , Sapium/química , Animais , Linhagem Celular , Cromatografia Líquida de Alta Pressão , Camundongos
17.
J Hematol Oncol ; 12(1): 103, 2019 10 17.
Artigo em Inglês | MEDLINE | ID: mdl-31623653

RESUMO

BACKGROUND: Circular RNAs (circRNAs) represent a type of endogenous noncoding RNAs that are generated by back-splicing events and favor repetitive sequences. Recent studies have reported that cancer-associated chromosomal translocations could juxtapose distant complementary repetitive intronic sequences, resulting in the aberrant formation of circRNAs. However, among the reported fusion genes, only a small number of circRNAs were found to originate from fusion regions during gene translocation. We question if circRNAs could also originate from fusion partners during gene translocation. METHODS: Firstly, we designed divergent primers for qRT-PCR to identify a circRNA circAF4 in AF4 gene and investigated the expression pattern in different types of leukemia samples. Secondly, we designed two small interfering RNAs specially targeting the back-spliced junction point of circAF4 for functional studies. CCK8 cell proliferation and cell cycle assay were performed, and a NOD-SCID mouse model was used to investigate the contribution of circAF4 in leukemogenesis. Finally, luciferase reporter assay, AGO2 RNA immunoprecipitation (RIP), and RNA Fluorescent in Situ Hybridization (FISH) were performed to confirm the relationship of miR-128-3p, circAF4, and MLL-AF4 expression. RESULTS: We discovered a circRNA, named circAF4, originating from the AF4 gene, a partner of the MLL fusion gene in MLL-AF4 leukemia. We showed that circAF4 plays an oncogenic role in MLL-AF4 leukemia and promotes leukemogenesis in vitro and in vivo. More importantly, knockdown of circAF4 increases the leukemic cell apoptosis rate in MLL-AF4 leukemia cells, while no effect was observed in leukemia cells that do not carry the MLL-AF4 translocation. Mechanically, circAF4 can act as a miR-128-3p sponge, thereby releasing its inhibition on MLL-AF4 expression. We finally analyzed most of the MLL fusion genes loci and found that a number of circRNAs could originate from these partners, suggesting the potential roles of fusion gene partner-originating circRNAs (named as FP-circRNAs) in leukemia with chromosomal translocations. CONCLUSION: Our findings demonstrate that the abnormal elevated expression of circAF4 regulates the cell growth via the circAF4/miR-128-3p/MLL-AF4 axis, which could contribute to leukemogenesis, suggesting that circAF4 may be a novel therapeutic target of MLL-AF4 leukemia.


Assuntos
Regulação Neoplásica da Expressão Gênica/fisiologia , Leucemia/genética , Proteína de Leucina Linfoide-Mieloide/metabolismo , Proteínas de Fusão Oncogênica/metabolismo , RNA Circular/metabolismo , Animais , Apoptose , Medula Óssea/metabolismo , Medula Óssea/patologia , Linhagem Celular , Proliferação de Células , Predisposição Genética para Doença , Humanos , Masculino , Camundongos , Camundongos SCID , MicroRNAs/genética , MicroRNAs/metabolismo , Proteína de Leucina Linfoide-Mieloide/genética , Neoplasias Experimentais , Proteínas de Fusão Oncogênica/genética
18.
Fitoterapia ; 133: 17-22, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30572085

RESUMO

Two new coumarinolignoids, sapiumins D (1) and E (2), a new lignanoid, lariciresinol 9'-benzoate (3), together with six known coumarinolignoids (4-9) and eight known lignanoids (10-17), were isolated from the stems and leaves of Sapium discolor. The structures of the isolated compounds were elucidated by extensive spectroscopic methods, including NMR, MS, and single crystal X-ray diffraction experiments. Compounds 5, 10, 11, and 13 significantly inhibited nitric oxide production in lipopolysaccharide-induced BV-2 microglial cells, with IC50 values in the range of 2.13-11.37 µM.


Assuntos
Cumarínicos/farmacologia , Lignina/farmacologia , Sapium/química , Animais , Cumarínicos/isolamento & purificação , Lignina/isolamento & purificação , Camundongos , Microglia/efeitos dos fármacos , Estrutura Molecular , Óxido Nítrico/biossíntese , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Folhas de Planta/química , Caules de Planta
19.
Bull Environ Contam Toxicol ; 102(1): 115-121, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30483838

RESUMO

Cyperus alternifolius (C. alternifolius) and Canna generalis (C. generalis) are widely used as artificial floating-bed (AFB) plants for water pollution control. This study evaluated the release of anti-cyanobacterial allelochemicals from both plants in AFB systems. A series of cyanobacterial assays using pure culture solutions and extracts of culture solutions of C. alternifolius and C. generalis demonstrated allelopathic growth inhibition of a cyanobacterium M. aeruginosa. After 45 days of incubation by the culture solutions, both final inhibitory rates of M. aeruginosa were more than 99.6% compared with that of the control groups. GC/MS analyses indicated the presence of a total of 15 kinds of compounds, including fatty acids and phenolic compounds, in both plants' culture solutions, which are are anti-cyanobacterial. These findings provide a basis to apply artificial floating-bed plants for cyanobacterial inhibition using allelopathic effects.


Assuntos
Alelopatia , Microcystis/efeitos dos fármacos , Feromônios/análise , Cyperus/química , Ácidos Graxos/análise , Cromatografia Gasosa-Espectrometria de Massas , Fenóis/análise , Extratos Vegetais/farmacologia , Zingiberales/química
20.
J Nat Prod ; 81(10): 2251-2258, 2018 10 26.
Artigo em Inglês | MEDLINE | ID: mdl-30350995

RESUMO

Seventeen compounds, including three new pairs of coumarinolignoid enantiomers, (7' S,8' S)-sapiumins A-C (1a-3a) and (7' R,8' R)-sapiumins A-C (1b-3b), six new taraxerane triterpenoids, sapiumic acids A-F (4-9), and five known taraxerane triterpenoids (10-14), were isolated from an ethanol extract prepared from the stems and leaves of Sapium discolor. The structures of 1-9 and their relative configurations were determined by spectroscopic data analysis, and the absolute configurations of the coumarinolignoids 1a/1b-3a/3b and triterpenoids 6-9 were assigned using experimental and calculated ECD data. Compounds 1a/1b-3a/3b are the first coumarinolignoids to be reported from the genus Sapium. Among all the isolates, compounds 1b, 2a/2b, 3a/3b, and 6-9 inhibited nitric oxide production in lipopolysaccharide-stimulated BV-2 microglial cells, with IC50 values of 1.7-15.3 µM.


Assuntos
Cumarínicos/isolamento & purificação , Cumarínicos/farmacologia , Microglia/metabolismo , Óxido Nítrico/biossíntese , Ácido Oleanólico/análogos & derivados , Sapium/química , Triterpenos/isolamento & purificação , Triterpenos/farmacologia , Linhagem Celular , Dicroísmo Circular , Humanos , Espectroscopia de Ressonância Magnética , Microglia/efeitos dos fármacos , Estrutura Molecular , Óxido Nítrico/antagonistas & inibidores , Ácido Oleanólico/isolamento & purificação , Ácido Oleanólico/farmacologia , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Folhas de Planta/química , Caules de Planta/química
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