ABSTRACT
N-Acetylgalactosamine (GalNAc)-conjugated small interfering RNA (siRNA) therapies have received approval for treating both orphan and prevalent diseases. To improve in vivo efficacy and streamline the chemical synthesis process for efficient and cost-effective manufacturing, we conducted this study to identify better designs of GalNAc-siRNA conjugates for therapeutic development. Here, we present data on redesigned GalNAc-based ligands conjugated with siRNAs against angiopoietin-like 3 (ANGPTL3) and lipoprotein (a) (Lp(a)), two target molecules with the potential to address large unmet medical needs in atherosclerotic cardiovascular diseases. By attaching a novel pyran-derived scaffold to serial monovalent GalNAc units before solid-phase oligonucleotide synthesis, we achieved increased GalNAc-siRNA production efficiency with fewer synthesis steps compared to the standard triantennary GalNAc construct L96. The improved GalNAc-siRNA conjugates demonstrated equivalent or superior in vivo efficacy compared to triantennary GalNAc-conjugated siRNAs.
Subject(s)
Cardiovascular Diseases , Hepatocytes , Humans , RNA, Small Interfering/genetics , RNA, Small Interfering/chemistry , Cost-Benefit Analysis , RNA, Double-Stranded , Acetylgalactosamine/chemistry , Angiopoietin-Like Protein 3ABSTRACT
BACKGROUND: Optical genome mapping (OGM) is a novel assay for detecting structural variants (SVs) and has been retrospectively evaluated for its performance. However, its prospective evaluation in prenatal diagnosis remains unreported. This study aimed to prospectively assess the technical concordance of OGM with standard of care (SOC) testing in prenatal diagnosis. METHODS: A prospective cohort of 204 pregnant women was enrolled in this study. Amniotic fluid samples from these women were subjected to OGM and SOC testing, which included chromosomal microarray analysis (CMA) and karyotyping (KT) in parallel. The diagnostic yield of OGM was evaluated, and the technical concordance between OGM and SOC testing was assessed. RESULTS: OGM successfully analyzed 204 cultured amniocyte samples, even with a cell count as low as 0.24 million. In total, 60 reportable SVs were identified through combined OGM and SOC testing, with 22 SVs detected by all 3 techniques. The diagnostic yield for OGM, CMA, and KT was 25% (51/204), 22.06% (45/204), and 18.14% (37/204), respectively. The highest diagnostic yield (29.41%, 60/204) was achieved when OGM and KT were used together. OGM demonstrated a concordance of 95.56% with CMA and 75.68% with KT in this cohort study. CONCLUSIONS: Our findings suggest that OGM can be effectively applied in prenatal diagnosis using cultured amniocytes and exhibits high concordance with SOC testing. The combined use of OGM and KT appears to yield the most promising diagnostic outcomes.
Subject(s)
Prenatal Diagnosis , Humans , Female , Pregnancy , Prospective Studies , Prenatal Diagnosis/methods , Adult , Karyotyping , Chromosome Mapping , Amniotic Fluid/chemistry , Amniotic Fluid/cytologyABSTRACT
Boron-doped graphdiyne (B-GDY) material exhibits an excellent performance in electrocatalysis, ion transport, and energy storage. However, accurately identifying the structures of B-GDY in experiments remains a challenge, hindering further selection of suitable structures with the most ideal performance for various practical applications. In the present work, we employed density functional theory (DFT) to simulate the X-ray photoelectron spectra (XPS) and near-edge X-ray absorption fine-structure (NEXAFS) spectra of pristine graphdiyne (GDY) and six representative single boron-doped graphdiynes at the B and C K-edges to establish the structure-spectroscopy relationship. A notable disparity in the C 1s ionization potentials (IPs) between substituted and adsorbed structures is observed upon doping with a boron atom. By analyzing the C and B 1s NEXAFS spectra on energy positions, spectral widths, spectral intensities, and different spectral profiles, we found that the six single boron-doped graphdiyne configurations can be sensitively identified. Moreover, this study provides a reliable theoretical reference for distinguishing different single boron-doped graphdiyne structures, enabling accurate selection of B-GDY structures for diverse practical applications.
ABSTRACT
BACKGROUND: Congenital heart disease (CHD) is the predominant birth defect. This study aimed to explore the association between maternal cardiovascular health (CVH) and the CHD risk in offspring. METHODS: We used the prospective data from the Fujian Birth Cohort Study, collected from March 2019 to December 2022 on pregnant women within 14 weeks of gestation. Overall maternal CVH was assessed by seven CVH metrics (including physical activity, smoking, sleep duration, body mass index, blood pressure, total cholesterol, and fasting plasma glucose), with each metric classified as ideal, intermediate or poor with specific points. Participants were further allocated into high, moderate and low CVH categories based on the cumulative CVH score. The association with offspring CHD was determined with log-binominal regression models. RESULTS: A total of 19810 participants aged 29.7 (SD: 3.9) years were included, with 7846 (39.6%) classified as having high CVH, 10949 (55.3%) as having moderate CVH, and 1015 (5.1%) as having low CVH. The average offspring CHD rate was 2.52%, with rates of 2.35%, 2.52% and 3.84% across the high, moderate and low CVH categories, respectively (P = 0.02). Adjusted relative risks (RRs) of having offspring CHD were 0.64 (95% CI: 0.45-0.90, P = 0.001) for high CVH and 0.67 (95% CI: 0.48-0.93, P = 0.02) for moderate CVH compared to low CVH. For individual metrics, only ideal total cholesterol was significantly associated with lower offspring CHD (RR: 0.73, 95% CI: 0.59-0.83, P = 0.002). CONCLUSIONS: Pregnant women of high or moderate CVH categories in early pregnancy had reduced risks of CHD in offspring, compared to those of low CVH. It is important to monitor and improve CVH during pre-pregnancy counseling and early prenatal care.
Subject(s)
Heart Defects, Congenital , Humans , Female , Pregnancy , Heart Defects, Congenital/epidemiology , Adult , Prospective Studies , China/epidemiology , Risk Factors , Birth Cohort , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/etiology , Maternal Health/statistics & numerical data , Pregnancy Complications, Cardiovascular/epidemiologyABSTRACT
OBJECTIVES: To investigate the clinical characteristics and prognosis of pneumococcal meningitis (PM), and drug sensitivity of Streptococcus pneumoniae (SP) isolates in Chinese children. METHODS: A retrospective analysis was conducted on clinical information, laboratory data, and microbiological data of 160 hospitalized children under 15 years old with PM from January 2019 to December 2020 in 33 tertiary hospitals across the country. RESULTS: Among the 160 children with PM, there were 103 males and 57 females. The age ranged from 15 days to 15 years, with 109 cases (68.1%) aged 3 months to under 3 years. SP strains were isolated from 95 cases (59.4%) in cerebrospinal fluid cultures and from 57 cases (35.6%) in blood cultures. The positive rates of SP detection by cerebrospinal fluid metagenomic next-generation sequencing and cerebrospinal fluid SP antigen testing were 40% (35/87) and 27% (21/78), respectively. Fifty-five cases (34.4%) had one or more risk factors for purulent meningitis, 113 cases (70.6%) had one or more extra-cranial infectious foci, and 18 cases (11.3%) had underlying diseases. The most common clinical symptoms were fever (147 cases, 91.9%), followed by lethargy (98 cases, 61.3%) and vomiting (61 cases, 38.1%). Sixty-nine cases (43.1%) experienced intracranial complications during hospitalization, with subdural effusion and/or empyema being the most common complication [43 cases (26.9%)], followed by hydrocephalus in 24 cases (15.0%), brain abscess in 23 cases (14.4%), and cerebral hemorrhage in 8 cases (5.0%). Subdural effusion and/or empyema and hydrocephalus mainly occurred in children under 1 year old, with rates of 91% (39/43) and 83% (20/24), respectively. SP strains exhibited complete sensitivity to vancomycin (100%, 75/75), linezolid (100%, 56/56), and meropenem (100%, 6/6). High sensitivity rates were also observed for levofloxacin (81%, 22/27), moxifloxacin (82%, 14/17), rifampicin (96%, 25/26), and chloramphenicol (91%, 21/23). However, low sensitivity rates were found for penicillin (16%, 11/68) and clindamycin (6%, 1/17), and SP strains were completely resistant to erythromycin (100%, 31/31). The rates of discharge with cure and improvement were 22.5% (36/160) and 66.2% (106/160), respectively, while 18 cases (11.3%) had adverse outcomes. CONCLUSIONS: Pediatric PM is more common in children aged 3 months to under 3 years. Intracranial complications are more frequently observed in children under 1 year old. Fever is the most common clinical manifestation of PM, and subdural effusion/emphysema and hydrocephalus are the most frequent complications. Non-culture detection methods for cerebrospinal fluid can improve pathogen detection rates. Adverse outcomes can be noted in more than 10% of PM cases. SP strains are high sensitivity to vancomycin, linezolid, meropenem, levofloxacin, moxifloxacin, rifampicin, and chloramphenicol.
Subject(s)
Empyema , Hydrocephalus , Meningitis, Pneumococcal , Subdural Effusion , Infant , Female , Male , Humans , Child , Infant, Newborn , Adolescent , Meningitis, Pneumococcal/drug therapy , Meningitis, Pneumococcal/epidemiology , Meropenem , Vancomycin , Levofloxacin , Linezolid , Moxifloxacin , Retrospective Studies , Rifampin , Streptococcus pneumoniae , ChloramphenicolABSTRACT
Objectiveï¼ To observe roproductive hormone levels in varicocele patients during a cycle (6 years) of Wu Yun Liu Qi, and explore whether the cycle had effect on the roproductive hormone levels. Methodsï¼ Data of roproductive hormone levels in varicocele patients from 2015 to 2020 were analyzed retrospectively. FSHãLHãTãPRLãE2 levels and T/E2 ratio were compared among the six years. According to Chinese sexagenary cycle heavenly stems and earthly branches of each year from 2015 to 2020 its yunqi characteristics were determined. Results: Totally data of 848 cases of varicocele patients were collected from 2015 to 2020. Among which, in 2015 (Yiwei year) there were 57 cases, in 2016 (Bingshen year) 83 cases, in 2017 (Dingyou year ) 133 cases, in 2018(Wuxu year) 156 cases, in 2019(Sihai year) 274 cases, and in 2020(Gengzi year) 145 cases. The levels of FSHãLHãPRLãT were not diferrent statistically from the six years except individual year. However, the level of E2 in 2016 when the Yunqi was Shao Yang Xiang Huo Si Tian and Jue Yin Feng Mu Zai Quan obviously higher than other years excpet 2018( All P< 0.05). And T/E2 ratio was lower in 2016 than other years except 2018 and 2020( All P< 0.05). Conclusions: Shi Xiang factors of Wu Yun Liu Qi had effect on roproductive hormone levels in varicocele patients, showing by higher E2 level in Yinshen year when the Shi Xiang factors may have bad effect on human fertility.
Subject(s)
Qi , Varicocele , Male , Humans , Retrospective Studies , Follicle Stimulating HormoneABSTRACT
OBJECTIVE: Diabetic foot ulcers (DFUs) are one of the most serious diabetic consequences, leading to amputations. Various therapies have been used to treat DFUs; however, a combination of negative pressure suction, artificial skin and autogenous skin implantation have never been investigated. This study aimed to evaluate the effectiveness of a novel three-step therapy protocol using negative pressure wound therapy (NPWT), artificial skin and autogenous skin implantation in patients with DFUs. METHOD: At a single tertiary university hospital between 2015 and 2018, the three-step therapy protocol was applied to patients with DFUs and its safety and efficacy was investigated. RESULTS: A total of 21 patients took part in the study. The majority of the patients were female (62%), with a mean age of 65 years and a mean body mass index of 21kg/m2. A third (n=7) of operative sites experienced minor complications, with two requiring re-operation. At a median follow up of 24 months, the average time of complete wound healing was 46 days, and the wound healing rate was 71%. The first-stage wound healing rate was 90%. All patients had achieved remission without any further recurrence of disease. CONCLUSION: This comprehensive surgical technique for managing DFUs achieved a high local cure rate, minimal functional morbidity, and acceptable wound complication rates. The three-step therapy protocol has the potential to promote the healing process of DFUs, which is expected to serve as a new method for the treatment and cure of DFUs.
Subject(s)
Diabetes Mellitus , Diabetic Foot , Negative-Pressure Wound Therapy , Skin, Artificial , Aged , Amputation, Surgical , Diabetic Foot/therapy , Female , Humans , Male , Wound HealingABSTRACT
Aim. To compare the safety and efficacy of computed tomography (CT)-assisted three-dimensional guiding templates (3DGTs) and free-hand (FH) technique for posterior cervical pedicle screw fixation in cervical spondylotic myelopathy (CSM) treatment. Methods. Thirty-five patients (216 screws) with CSM and developmental cervical stenosis were randomly divided into groups A (FH) and B (3DGTs). All patients underwent modified posterior surgery with cervical pedicle screw insertion (C1-7). Preoperative, postoperative, and intergroup comparisons of efficacy were evaluated using the visual analog scale (VAS), Japanese Orthopaedic Association (JOA), and Short Form 12 (SF-12) scores and JOA score improvement rate. Incidence of intra- and postoperative complications was analyzed. Postoperative cervical spine CT was performed to evaluate (i) the pedicle screws' deviation angle from the optimal path (sagittal deviation, α; coronal deviation angle, ß), screw insertion point's deviation distance (d), and screw accuracy and (ii) the deviation angle and distance of screw entrance point of pedicle screws from the optimal channel. Results. All patients successfully completed the procedures. Groups A and B did not significantly differ in age, sex ratio, body mass index, operative time, or intraoperative blood loss amount. Postoperative VAS, JOA, and SF-12 scores improved in both groups. VAS, JOA, or SF-12 scores did not significantly differ between the 2 groups. The α, ß, and d scores were lower in group B, but accuracy was higher in group B. Conclusions. 3DGTs and FH technique show comparable outcomes with respect to neurological improvement and safety.
Subject(s)
Pedicle Screws , Humans , Retrospective Studies , Cervical Vertebrae/diagnostic imaging , Cervical Vertebrae/surgery , Tomography, X-Ray Computed/methods , Operative Time , Treatment OutcomeABSTRACT
Thermochromic smart windows technology can intelligently regulate indoor solar radiation by changing indoor light transmittance in response to thermal stimulation, thus reducing energy consumption of the building. In recent years, with the development of new energy-saving materials and the combination with practical technology, energy-saving smart windows technology has received more and more attention from scientific research. Based on the summary of thermochromic smart windows by Yi Long research groups, this review described the applications of thermal responsive organic materials in smart windows, including poly(N-isopropylacrylamide) (PNIPAm) hydrogels, hydroxypropyl cellulose (HPC) hydrogels, ionic liquids and liquid crystals. Besides, the mechanism of various organic materials and the properties of functional materials were also introduced. Finally, opportunities and challenges relating to thermochromic smart windows and prospects for future development are discussed.
ABSTRACT
Cimicifuga dahurica (Turcz.) Maxim, which is also regarded as the main origin of "Shengma" in the Chinese Pharmacopoeia, has been used as a cooling and detoxification agent for thousands of years. Our previous phytochemical investigations of C. dahurica extracts (CDEs) led to the isolation of a series of 9,19-cycloalkane triterpenoids and phenolic acids showing a potential anti-inflammatory activity. However, the chemical profiling of CDEs and the material basis of its anti-inflammatory effect in vivo has not been clarified. In the present study, the CDE chemical profile and prototype components in rat plasma were identified via ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. As a result, a total of 106 components were identified or tentatively characterized in CDEs, including 54 triterpenoids, 35 phenolic acids, eight amides and nine other type constituents (39 compounds were confirmed with the reference standards). In addition, 20 prototype components (15 triterpenoids and five phenolic acids) were identified in rat plasma, which potentially related to the anti-inflammatory effects of CDEs. Moreover, the anti-inflammatory activities of the main prototype components were further evaluated by their inhibitory effects on the production of NO, as well as the expressions of iNOS and COX-2 in lipopolysaccharide-stimulated RAW264.7 cells, which indicated that 9,19-cycloalkane triterpenoids may play an anti-inflammatory role by down-regulating the expression of iNOS.
Subject(s)
Anti-Inflammatory Agents , Cimicifuga/chemistry , Network Pharmacology/methods , Plant Extracts , Animals , Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/pharmacology , Cell Survival/drug effects , Chromatography, High Pressure Liquid/methods , Mass Spectrometry/methods , Mice , Plant Extracts/chemistry , Plant Extracts/pharmacology , RAW 264.7 Cells , Rats , Triterpenes/analysis , Triterpenes/chemistry , Triterpenes/pharmacologyABSTRACT
Jin-hong tablets (JHTs), a well-known traditional Chinese patent medicine (TCPM), have been effectively used for the treatment of chronic superficial gastritis (CSG). The metabolic profile of TCPMs is performed to determine their bioactive components. In this study, a five-step strategy based on ultra-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry and metabolynx™ software combined with mass defect filter technique was developed to delineate the metabolic profile of JHT in vivo. As a result, a total of 163 JHT-related xenobiotics (38 prototypes and 125 metabolites) were identified or tentatively characterized in rat biological samples, and the phase I and II metabolism processes mainly included demethylation, hydroxylation, sulfation, and glucuronidation. In addition, after oral administration of JHT, a large amount of alkaloid-related ingredients was detected in rat plasma samples, indicating that alkaloids may play an important role in the treatment of CSG with JHT. This study is beneficial for understanding the JHT's in vivo metabolic profiles and characteristics, which helps to reveal its in vivo effective components and provides a solid basis for further studies on its functional mechanism.
Subject(s)
Alkaloids , Chromatography, High Pressure Liquid/methods , Drugs, Chinese Herbal , Tandem Mass Spectrometry/methods , Administration, Oral , Alkaloids/analysis , Alkaloids/chemistry , Alkaloids/metabolism , Animals , Berberine Alkaloids , Bile/chemistry , Drugs, Chinese Herbal/administration & dosage , Drugs, Chinese Herbal/metabolism , Feces/chemistry , Flavonoids/analysis , Flavonoids/chemistry , Flavonoids/metabolism , Male , Rats , Rats, Sprague-Dawley , TabletsABSTRACT
Subsurface wastewater infiltration (SWI) is an environmentally friendly technology for the advanced treatment of domestic sewage. Clogging (including physical, chemical and biological clogging) of the porous medium not only directly reduces the hydraulic load (treatment efficiency), but also reduces the service life. Although clogging has become one of the key issues discussed in several reports, there are still several gaps in understanding, especially in its occurrence process and identification. SWI clogging causes, development process and solutions are different from those of constructed wetlands. This article quotes some reports on constructed wetlands to provide technical ideas and reference for revealing SWI clogging problems. Based on the analysis of the clogging genesis, this review gathers the main factors that affect the degree of clogging, and new methods for the identification of clogging conditions. Some preventive and unclogging measures/strategies are presented. Finally, it is suggested that to effectively alleviate the clogging phenomenon and extend the service life, priority should be given to the comprehensive analysis of wastewater quality and solid constituents accumulated in the pores. Then, the effectiveness of in-situ strategies, such as alternating operation will be the main focuses of future research.
Subject(s)
Waste Disposal, Fluid , Wastewater , Porosity , Sewage , WetlandsABSTRACT
Objective: To evaluate preoperative comprehensive examinations of the IPSS-voiding to storage subscore ratio (IPSS-V/S), maximum urinary flow rate (Qmax), intravesical prostatic protrusion (IPP) and postvoid residual urine volume (PVR) in predicting the outcome of transurethral resection of the prostate (TURP) for BPH. METHODS: This retrospective study included 103 cases of BPH treated by TURP in Yixing People's Hospital from December 2018 to December 2019. The patients averaged 71.92 ± 7.73 years of age, with a mean prostate volume of (58.34 ± 15.59) ml, preoperative IPSS of 23.38 ± 3.36, voiding score of 14.38 ± 2.69, storage score of 9 (8ï¼10), V/S ratio of 1.67 (1.43ï¼1.88), Qmax of 7 (5ï¼8) ml/s, IPP of 4 (0ï¼5) mm, and PVR of (117.03 ± 20.51) ml. The TURP operations were completed by the same surgeon, with mean operation time of (83.65 ± 14.31) min and intraoperative blood loss of (55.32 ± 18.92) ml. The patients were followed up for 3 months after surgery for evaluation of the outcomes based on the IPSS and quality of life (QOL) scores. RESULTS: The postoperative IPSS was significantly improved in all the patients compared with the baseline (5.36 ± 1.95 vs 23.38 ± 3.36, P < 0.05). Based on the criteria of IPSS < 7 and general satisfaction with QOL, satisfactory results were achieved in 71 (68.93%) of the patients (aged 71.04 ± 7.23 years, prostate volume: ï¼»59.68 ± 15.79ï¼½ ml, IPSS: 23.87 ± 3.42, voiding score: 14.87 ± 2.34, storage score: 9 ï¼»8ï¼10ï¼½, V/S ratio: 1.67 ï¼»1.47ï¼1.86ï¼½, Qmax: 6 ï¼»4ï¼7ï¼½ ml/s, IPP: 5 ï¼»0ï¼6ï¼½ mm, PVR: 110.53 ± 17.69 ml, operation time ï¼»85.37 ± 12.28ï¼½ min, intraoperative blood loss: ï¼»58.08 ± 14.61ï¼½ ml), and unsatisfactory results in the other 32 (31.07%) (aged 76.91 ± 8.25 years, prostate volume: ï¼»55.38 ± 14.73ï¼½ ml, IPSS: 22.53 ± 3.25, voiding score: 13.53 ± 3.21, storage score: 9 ï¼»8ï¼12ï¼½, V/S ratio: 1.36 ï¼»1.03ï¼1.95ï¼½, Qmax: 8 ï¼»7ï¼9ï¼½ ml/s, IPP: 0 ï¼»0ï¼5ï¼½ mm, PVR: ï¼»129.61 ± 20.62ï¼½ ml, operation time: ï¼»78.85 ± 10.04ï¼½ min, intraoperative blood loss: 48.76 ± 12.19 ml). CONCLUSIONS: TURP yields better results in younger BPH patients, with baseline IPSS dominantly in urinary symptoms, greater IPP, lower PVR, and lower Qmax.
ABSTRACT
Chemical constituents were isolated and purified from the water extract of Artemisia annua by column chromatography of HP-20 macroporous resin, silica gel, ODS, Sephadex LH-20, HW-40, and semi-preparative RP-HPLC. Their structures were elucidated by physicochemical properties and spectral analyses. As a result, Fifteen compounds were isolated and identified as vitexnegheteroin M(1), sibricose A5(2), securoside A(3), citrusin D(4), annphenone(5), E-melilotoside(6), esculetin(7), scopoletin-7-O-ß-D-glucoside(8), eleutheroside B_1(9), chrysosplenol D(10), patuletin-3-O-ß-D-glucopyranoside(11), quercetin-7-O-ß-D-glucoside(12), rutin(13), apigenin 6,8-di-C-ß-D-glucopyranoside(14), isoschaftoside(15), among them, compounds 1-4 were identified from Artemisia for the first time. Additionally, the isolates were evaluated for their inhibitory effects on the production of PGE_2 in LPS-simulated RAW264.7 macrophages. The results showed that compounds 1, 2, 8, and 10-15 could reduce PGE_2 levels, to a certain extent.
Subject(s)
Artemisia annua , Apigenin , Quercetin , RutinABSTRACT
Direct conversion of the readily available alkyl bromides and alcohols to value-added epoxides using dimethyl sulfoxide (DMSO) under mild reaction conditions has been developed. Benzyl and allyl bromides, and activated and unactivated alcohols all proceeded smoothly to give epoxides in high to excellent yield. Dimethyl sulfide, generated by DMSO oxidations, was in situ elaborated to form the substituted dimethyl sulfonium ylide species that participates in the Corey-Chaykovsky epoxidation in a domino and one-pot fashion, respectively.
ABSTRACT
Thirteen new sesquiterpenoids, arteannoides F-R (1-13), along with 13 known analogues (14-26), were isolated from the dried aerial parts of Artemisia annua L. Their structures, including absolute configurations, were unambiguously determined by a combination of physical data analyses (HRESIMS, 1D and 2D NMR, and ECD) as well as the crystal structures of 1, 5, 6, 15, 19, and 23. Among the isolated compounds, 1 features an unusual 11-oxatricyclo[6.2.1.04,9]undecan-2-ene ring system, 5 possesses an uncommon 4,11-ether bridged tricyclic framework, whereas 6 is a new eudesmane-type sesquiterpenoid formed via rearrangement of its carbon backbone. The systemically anti-inflammatory activities of all isolates were evaluated by measuring their inhibitory effects on PGE2, NO, TNF-α, and IL-6 production in LPS-stimulated RAW 264.7 macrophages. Moreover, the structure activity relationships of some compounds are summarized, this study will provide new structural templates for discovering potential anti-inflammatory agents.
Subject(s)
Anti-Inflammatory Agents/pharmacology , Artemisia annua/chemistry , Plant Components, Aerial/chemistry , Sesquiterpenes, Eudesmane/pharmacology , Animals , Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/isolation & purification , Dinoprostone/antagonists & inhibitors , Interleukin-6/antagonists & inhibitors , Mice , Molecular Structure , Nitric Oxide/antagonists & inhibitors , RAW 264.7 Cells , Sesquiterpenes, Eudesmane/chemistry , Sesquiterpenes, Eudesmane/isolation & purification , Structure-Activity Relationship , Tumor Necrosis Factor-alpha/antagonists & inhibitorsABSTRACT
In order to analyze the expression of genes involved in steroidal saponin biosynthesis pathway in Polygonatum cyrtonema tubers, it is very important to select internal reference genes that are stably expressed at different development stages and in response to abiotic stress. According to the previously established P. cyrtonema transcriptome database and reported internal reference genes in plant, this study systematically analyzed eight candidate internal reference genes including histone H2 A, glyceraldehyde-3-phosphate dehydrogenase, ACTIN, ß-tubulin, ubiquitin-conjugating enzyme-E2-10, elongation factor 1-alpha isoform, 18 S rRNA and α-tubulin 4 for expression stability in P. cyrtonema tubers at different development stages and in response to methyl jasmonate(MeJA) stress by using Real time fluorescence quantitative PCR(qPCR). Based on the statistical analysis of qPCR results by using GeNorm, NormFinder and BestKeeper softwares, the expression of ubiquitin-conjugating enzyme-E2-10 and elongation factor 1-alpha isoform are the most stable in P. cyrtonema tubes at different development stages and in response to MeJA stress. The two internal reference genes were further validated by analyzing the expression of 4 genes involved in steroidal saponin biosynthesis pathways. In conclusion, ubiquitin-conjugating enzyme-E2-10 and elongation factor 1-alpha isoform can be used as the most appropriate internal reference genes for qPCR analysis in P. cyrtonema. This study also provide a foundation for future investigate the molecular mechanism of steroidal saponin biosynthesis pathways in P. cyrtonema.
Subject(s)
Polygonatum , Gene Expression Profiling , Real-Time Polymerase Chain Reaction , Stress, Physiological , TranscriptomeABSTRACT
To enrich the transcriptome data in rhizome of Polygonatum cyrtonema seedlings, identify candidate functional genes involved in steroidal saponin biosynthesis and provide genetic resources for the research on anabolism pathway and regulatory mechanism of active components in P. cyrtonema, Illumina platform was applied to perform transcriptomic sequencing of rhizome of P. cyrtonema, followed by a series of bioinformatics analysis on RNA-seq data, including de novo assembly, annotation, classification and metabolic pathway analysis of the assembled unigene. Meanwhile, a deep analysis on the steroidal saponin biosynthesis in secondary metabolism pathway was performed. The results showed a total of 126 546 unigene were obtained by de novo transcriptome assembly, of which 47 226 were annotated. Of these, 16 499 unigene were mapped to 132 specific pathways, of which 2 768 were identified to be involved in 22 secondary metabolic pathways. One hundred and thirteen unigene were identified from the transcriptome database, which encoded 27 metabolic enzymes associated with steroidal saponin biosynthesis and shared similarity with 45 functional genes in Arabidopsis thaliana. In conclusion, a series of candidate functional genes, which might be involved in steroidal saponin biosynthesis, were selected from the transcriptome database of P. cyrtonema rhizome. Further investigation of these candidate genes will provide insight into their actual functions in the steroidal saponin biosynthetic pathway in P. cyrtonema. In addition, this study also provide abunant reference data for transcriptome characterization of P. cyrtonema and has important significance for functional genomics of P. cyrtonema.
Subject(s)
Polygonatum , Biosynthetic Pathways , Gene Expression Profiling , Rhizome , Saponins , TranscriptomeABSTRACT
OBJECTIVE: To study the value of body fat mass measured by bioelectrical impedance analysis (BIA) in predicting abnormal blood pressure and abnormal glucose metabolism in children. METHODS: Stratified cluster sampling was used to select the students aged 6-16 years, and a questionnaire survey and physical examination were performed. The BIA apparatus was used to measure body fat mass. Body mass index (BMI), body fat mass index (FMI), and fat mass percentage (FMP) were calculated. Fasting blood glucose level were measured. RESULTS: A total of 14â293 children were enrolled, among whom boys accounted for 49.89%. In boys and girls, the percentile values (P60, P65, P70, P75, P80, P85, P90, P95) of FMI and FMP fitted by the LMS method were taken as the cut-off values. Based on the receiver operating characteristic curve analysis, the P70 values with a better value in predicting abnormal blood pressure and blood glucose metabolism were selected as the cut-off values for excessive body fat. When FMI or FMP was controlled below P70, the incidence of abnormal blood pressure or abnormal glucose metabolism may be decreased in 8.25%-43.24% of the children. CONCLUSIONS: The evaluation of obesity based on FMI and FMP has a certain value in screening for hypertension and hyperglycemia in children, which can be further verified in the future prevention and treatment of obesity and related chronic diseases in children.
Subject(s)
Adipose Tissue , Adolescent , Blood Pressure , Body Composition , Body Mass Index , Child , Electric Impedance , Female , Glucose , Humans , MaleABSTRACT
Five new phenylpropanoid allopyranosides (1-5), along with five known compounds (6-10) were isolated from the rhizomes of Cimicifuga dahurica. Their structures were established by means of spectroscopic analyses and chemical methods, as well as comparison with literatures. The anti-inflammatory activities of all isolates were evaluated. Compounds 6, 9 and 10 exhibited inhibitory effects on PGE2 production in LPS stimulated RAW 264.7 macrophages with IC50 values of 19.72, 6.33 and 39.90⯵M, respectively.