ABSTRACT
BACKGROUND: It is challenging to improve the effects of chemotherapy and reduce its adverse impact on the ovaries. Our previous study suggested that the combination of galaxamide could enhance the antitumor effect of cisplatin (CIS) in HeLa cell xenograft mice. However, their potential effects on ovarian tissues remain unknown. METHODS: The Hela tumor-bearing female BALB/c mice model was established and randomly divided into three groups: control group (PBS group), CIS group (0.3 mg/kg CIS group) and galaxamide group (0.3 mg/kg CIS + 3 mg/kg galaxamide-treated group). The serum sex hormones levels, ovarian morphology, functional and molecular characterisation were determined and compared with those of the control group. RESULTS: The hormonal effects indicated premature ovarian insufficiency (POI) associated with CIS-induced tumor-bearing mice. CIS induces the apoptosis in primordial and developing follicles and subsequently increases follicular atresia, eventually leading to follicle loss. After cotreatment, galaxamide significantly increased anti-Mullerian hormone (AMH) and follicle-stimulating hormone receptor (FSHR) expression and prevented the CIS-induced PI3K pathway, which triggers follicle activation, apoptosis or atresia. CONCLUSION: These findings demonstrate that galaxamide could attenuate CIS-induced follicle loss by acting on the PI3K signaling pathway by stimulating AMH and/or FSHR and thus provides promising therapeutic options for patients with cervical cancer.
Subject(s)
Cisplatin , Phosphatidylinositol 3-Kinases , Primary Ovarian Insufficiency , Signal Transduction , Animals , Primary Ovarian Insufficiency/chemically induced , Primary Ovarian Insufficiency/drug therapy , Primary Ovarian Insufficiency/metabolism , Female , Humans , Mice , Cisplatin/adverse effects , Signal Transduction/drug effects , HeLa Cells , Phosphatidylinositol 3-Kinases/metabolism , Mice, Inbred BALB C , Apoptosis/drug effects , Xenograft Model Antitumor Assays , Anti-Mullerian Hormone/blood , Anti-Mullerian Hormone/metabolism , Antineoplastic Agents/pharmacology , Uterine Cervical Neoplasms/drug therapy , Uterine Cervical Neoplasms/metabolism , Uterine Cervical Neoplasms/pathology , Receptors, FSH/metabolism , Receptors, FSH/geneticsABSTRACT
A new steroid, 2a-oxa-2-oxo-5ß-hydroxy-3,4-dinor-24-methylcholesta-22E-ene (1), together with 10 known ones (2-11), was isolated from the marine sponge Cliona sp. The structures of these compounds were determined by the spectroscopic methods (UV, IR, MS, and NMR) and X-ray diffraction analysis. Compound 1 was the third example of 3,4-dinorsteroid with a hemiketal at C-5 that was isolated from the natural source. In addition, the antibacterial activities of these compounds were also evaluated. However, none of them exhibited significant inhibition effects.
Subject(s)
Anti-Bacterial Agents , Marine Biology , Porifera , Animals , Porifera/chemistry , Molecular Structure , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/isolation & purification , Microbial Sensitivity Tests , Nuclear Magnetic Resonance, Biomolecular , Steroids/chemistry , Steroids/pharmacology , Steroids/isolation & purification , Crystallography, X-RayABSTRACT
BACKGROUND: We aimed to observe the dynamic changes in glucose metabolic reprogramming-related parameters and their ability to predict neurological prognosis and all-cause mortality in cardiac arrest patients after the restoration of spontaneous circulation (ROSC). METHODS: Adult cardiac arrest patients after ROSC who were admitted to the emergency or cardiac intensive care unit of the First Affiliated Hospital of Dalian Medical University from August 1, 2017, to May 30, 2021, were enrolled. According to 28-day survival, the patients were divided into a non-survival group (n=82) and a survival group (n=38). Healthy adult volunteers (n=40) of similar ages and sexes were selected as controls. The serum levels of glucose metabolic reprogramming-related parameters (lactate dehydrogenase [LDH], lactate and pyruvate), neuron-specific enolase (NSE) and interleukin 6 (IL-6) were measured on days 1, 3, and 7 after ROSC. The Acute Physiology and Chronic Health Evaluation II (APACHE II) score and Sequential Organ Failure Assessment (SOFA) score were calculated. The Cerebral Performance Category (CPC) score was recorded on day 28 after ROSC. RESULTS: Following ROSC, the serum LDH (607.0 U/L vs. 286.5 U/L), lactate (5.0 mmol/L vs. 2.0 mmol/L), pyruvate (178.0 µmol/L vs. 70.9 µmol/L), and lactate/pyruvate ratio (34.1 vs. 22.1) significantly increased and were higher in the non-survivors than in the survivors on admission (all P<0.05). Moreover, the serum LDH, pyruvate, IL-6, APACHE II score, and SOFA score on days 1, 3 and 7 after ROSC were significantly associated with 28-day poor neurological prognosis and 28-day all-cause mortality (all P<0.05). The serum LDH concentration on day 1 after ROSC had an area under the receiver operating characteristic curve (AUC) of 0.904 [95% confidence interval [95% CI]: 0.851-0.957]) with 96.8% specificity for predicting 28-day neurological prognosis and an AUC of 0.950 (95% CI: 0.911-0.989) with 94.7% specificity for predicting 28-day all-cause mortality, which was the highest among the glucose metabolic reprogramming-related parameters tested. CONCLUSION: Serum parameters related to glucose metabolic reprogramming were significantly increased after ROSC. Increased serum LDH and pyruvate levels, and lactate/pyruvate ratio may be associated with 28-day poor neurological prognosis and all-cause mortality after ROSC, and the predictive efficacy of LDH during the first week was superior to others.
ABSTRACT
A mild protocol for electrochemically oxidative fluorodifunctionalization of styrenes has been demonstrated. The reaction proceeds under metal, external oxidant, and catalyst free conditions, allowing tunable access to a wide variety of synthetically useful fluoroalkyl derivatives, such as ß-fluorosulfone/fluoromethyl, fluorothiocyanation, and vinylsulfonyl derivatives. Moreover, CsF was shown to be the proper fluorine source for this electrochemical fluorodifunctionalization transformation.
ABSTRACT
The waste slag known as jarosite residue (JR) and arsenic sulfide residue (ASR) were produced following the creation of zinc by hydrometallurgical procedures. The increasing annual zinc mining has led to growing pressure to dispose of the resulting JR and ASR from zinc smelting, making it crucial to assess their environmental impact and feasibility for utilization. The main components, distribution characteristics of elements, and potential environmental risks of zinc smelting wastes are studied through toxicity leaching tests, sequential extraction procedures, and various characterization technologies such as XRF, XRD, and SEM-EDS. The mineral compositions of JR are natrojarosite, franklinite, and gunningite, and zinc mainly adheres to the crevices of the natrojarosite mineral. Meanwhile, the ASR of flocculent structures is composed of orpiment, greenockite, arsenic oxide, and calvertite, and As appears in the form of the S-As-O phase. The Zn, Cu, and Cd in JR were dominated by exchangeable bound (81.53-96.6 %), and the main form of As, Cd, Se, and Tl in ASR was organic matter bound (87.0-99.21 %). The Risk Assessment Code (RAC) method confirmed the risk of Cd, Cu, Zn, and Mo in JR is high, while the risk of Cd, Pb, and Cr in ASR is moderate. Compared to the standard value of "Identification Standard for Toxicity of Hazardous Waste Leaching (GB5085.3-2007)", the leachate concentrations of Zn in JR as well as Cd and As in ASR were exceeded, suggesting that the JR and ASR were in the type of hazardous waste and posed an environmental risk. The study provides theoretical guidance for the future rational management and effective utilization of hazardous waste.
ABSTRACT
Four new cytochalasans, marchaetoglobins A-D (1-4), along with five known compounds (5-9), were isolated from the marine-sponge-associated fungus Chaetomium globosum 162105. Compounds 1-4 represent examples of 19,20-seco-chaetoglobosins, of which compound 1 is the first furan-containing cytochalasan. Their structures and absolute configurations were elucidated by extensive spectroscopic analyses and electronic circular dichroism calculations. Compounds 5, 8, and 9 displayed weak to moderate antibacterial activities against Bacillus thuringiensis, Edwardsiella piscicida, Vibrio alginolyticus, and Pseudomonas syringae pv. actinidiae with minimum inhibitory concentration values ranging from 5 to 25 µg/mL. In addition, compounds 2, 3, and 5 showed potent in vivo proangiogenic activity in transgenic zebrafish, comparable to the positive control.
ABSTRACT
Two new cytochalasans, marcytoglobosins A (1) and B (2) were isolated from the marine sponge associated fungus Chaetomium globosum 162105, along with six known compounds (3-8). The complete structures of two new compounds were determined based on 1D/2D NMR and HR-MS spectroscopic analyses coupled with ECD calculations. All eight isolates were evaluated for their antibacterial activity. Among them, compounds 3-8 displayed antibacterial effects against Staphylococcus epidermidis, Bacillus thuringiensis, Pseudomonas syringae pv. Actinidiae, Vibrio alginolyticus, and Edwardsiella piscicida with minimum inhibitory concentration (MIC) values ranging from 10 to 25â µg/mL.
Subject(s)
Anti-Bacterial Agents , Chaetomium , Microbial Sensitivity Tests , Porifera , Chaetomium/chemistry , Animals , Porifera/microbiology , Porifera/chemistry , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/isolation & purification , Cytochalasins/pharmacology , Cytochalasins/chemistry , Cytochalasins/isolation & purification , Molecular ConformationABSTRACT
A chemical investigation on the marine sponge Dysidea sp. resulted in the isolation of a series of diketopiperazines, including two new compounds, dysidines A (1) and B (2) as well as six known ones (3-8). Their structures with absolute configurations were determined on the basis of UV, IR, HRMS, NMR and calculated ECD method. Additionally, the cytotoxic, anti-inflammatory, antibacterial and antiviral activities of 1-8 were also tested. However, none of them exhibited significant bioactivities.
ABSTRACT
Marine natural products continue to hold great promise as potential candidates for the discovery of anti-inflammatory drug. In our previous investigation, we successfully synthesized axinelline A, a naturally occurring cyclooxygenase-2 (COX-2) inhibitor, as a promising anti-inflammatory lead compound. This study was to discover novel COX inhibitors with balanced inhibition, aiming to mitigate the severe adverse effects through further structural modification of axinelline A. Of the synthetic derivatives, compound 5e showed highest COX-2 inhibitory activity and balanced COX inhibition (IC50 = 1.74 µM; selectivity ((IC50 (COX-1)/IC50(COX-2) = 16.32). The in vitro anti-inflammatory results indicated that 5e effectively suppressed the expression of pro-inflammatory mediators via the NF-κB signaling pathway rather than the MAPK signaling pathway. The in vivo ulcerative colitis assay demonstrated 5e significantly ameliorated the histological damages and showed strong protection against DSS-induced acute colitis. Therefore, our findings suggest that compound 5e exhibits potential as a promising anti-inflammatory agent with attenuated colitis-related adverse effects.
Subject(s)
Catechols , Colitis , Humans , Cyclooxygenase 2/metabolism , Colitis/chemically induced , Colitis/drug therapy , NF-kappa B/metabolism , Anti-Inflammatory Agents/adverse effects , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Cyclooxygenase 2 Inhibitors/pharmacologyABSTRACT
Industrial by-products are stored in large quantities in the open, leading to wasted resources and environmental pollution, and the natural environment is similarly faced with phosphate depletion and serious water and soil pollution. This study uses these by-products to produce a new sludge/biomass ash ceramsite that will be used to adsorb nitrogen and phosphorus from wastewater, and solidify heavy metals in the soil while releasing Olsen P. The sludge/biomass ash ceramsites are made using sewage sludge and biomass ash in a certain ratio calcined at high temperatures and modified for the adsorption of nitrogen and phosphorus from wastewater. Sludge/biomass ash ceramsites before and after phosphorus adsorption, biochar and biomass ash were compared to analyze their heavy metal adsorption capacity and potential as phosphate fertilizer. After phosphorus adsorption, the sludge/biomass ash ceramsites released effective phosphorus steadily and rapidly in the soil, with a greater initial release than biochar and biomass ash, and the ceramsites were in a granular form that could be easily recycled. Biochar and biomass residue, due to their surface functional groups, are better at solidifying heavy metals than sludge/biomass ash ceramsites. Biochar, biomass ash and sludge/biomass ash ceramsites significantly reduced the concentrations of Cd, Cu, Pb and Zn in the soil. Correlation analysis demonstrated that there was a synergistic relationship between the increase in soil Olsen P content and the change in pH, with the increase in soil Olsen P content and the increase in pH contributing to heavy metal solidification.
Subject(s)
Complex Mixtures , Metals, Heavy , Soil Pollutants , Sewage/chemistry , Wastewater , Biomass , Metals, Heavy/analysis , Charcoal/chemistry , Soil/chemistry , Phosphorus/analysis , Phosphates/analysis , Nitrogen/analysis , Soil Pollutants/analysisABSTRACT
Herein, an unprecedented cadmium-based metal-organic framework (JNU-106) fabricated by utilizing pyrazole-functionalized tetraphenylethylene ligands (Py-TPE) and rod-shaped secondary building units is reported, possessing a new (3,3,3,6,6,8)-connected topological network. Thanks to the ingeniously designed intramolecular charge transfer behavior, which originates from the congruent coplanarity between Py and TPE, JNU-106 exhibits intense green luminescence with a quantum yield increased by 1.5 times. The phenomenon of remarkable fluorescence quenching of JNU-106 reveals that it possesses extremely high anti-interference performance, superior sensitivity, and dedicated selectivity toward tetracycline antibiotics (TCAs) in aqueous solutions, which are comparable to those of the state-of-the-art porous sensing compounds. Taking the theoretical calculations and experimental results into account, the luminescence quenching is mainly attributed to the internal filtration effect and the static quenching effect. Considering the portable and rapid performance of JNU-106-based testing strips for sensing TCAs, the fabricated JNU-106 provides an alternative for ecological monitoring and environmental governance.
ABSTRACT
(+)- and (-)-Tedanine [(+)-1 and (-)-1], a pair of new enantiomeric indolone alkaloids, along with nine compounds (2-10) were isolated from the marine sponge Tedania sp. The structures of (+)-1 and (-)-1 including absolute configurations were determined by spectroscopic analysis and quantum chemical calculation. Compounds (+)-1 and (-)-1 were the first examples of indolone alkaloids isolated from this genus. In addition, the cytotoxic and antibacterial activities of these compounds were also evaluated.
Subject(s)
Alkaloids , Antineoplastic Agents , Porifera , Animals , Porifera/chemistry , Alkaloids/chemistry , Anti-Bacterial Agents/chemistry , Antineoplastic Agents/chemistry , Molecular StructureABSTRACT
A new piperidone alkaloid, dysidone A (1), was isolated from the marine sponge Dysidea sp. The structure of 1 was elucidated by the method of spectroscopic analysis. Compound 1 represented the first example of piperidone alkaloid isolated from the sponge of the genus Dysidea with the exocyclic double bond. Furthermore, the total synthesis of 1 was also carried out, which was started with piperidine proceeding a PIDA/I2-mediated α and ß-C (sp3) -H bond dual oxygenation to achieve a 5-steps synthesis in a total yield of 10.6%. In addition, the anti-inflammatory activities of 1 and its derivative dysidone B (1d) were evaluated, which suggested that 1 showed weak anti-inflammatory activity.
ABSTRACT
Myocardial ischemia/reperfusion (I/R) injury after the onset of acute myocardial infarction (AMI) can be life-threatening, and there is no effective strategy for therapeutic intervention. Here, we studied the potential of protectin D1 in protecting from I/R-induced cardiac damages and investigated the underlying mechanisms. An in vivo rat model of I/R after AMI induction was established through the ligation of the left anterior descending (LAD) artery to assess the cardiac functions and evaluate the protective effect of protectin D1. Protectin D1 protected against I/R-induced oxidative stress and inflammation in the rat model, improved the cardiac function, and reduced the infarct size in myocardial tissues. The beneficial effect of protectin D1 was associated with the up-regulation of miRNA-210 and the effects on PI3K/AKT signaling and HIF-1α expression. Together, our data suggest that protectin D1 could serve as a potential cardioprotective agent against I/R-associated cardiac defects.
ABSTRACT
Two new pairs of enantiomeric butenolides, (+)- and (-)-suberiteslide A, (+)- and (-)-subertieslide B had been obtained from the marine sponge Suberties sp. The structures with absolute configurations of these compounds were unequivocally determined by spectroscopic analyses and ECD (Electronic Circular Dichroism) method. It was the first separation of butenolides from the marine sponges of genus Suberites. Additionally, the anti-inflammatory, antibacterial and cytotoxic activities of these compounds were evaluated. The result indicated that only (-)-subertieslide B showed weak anti-inflammatory activity with the IC50 value of 40.8â µM.
Subject(s)
Porifera , Animals , Porifera/microbiology , 4-Butyrolactone/chemistry , Anti-Bacterial Agents/pharmacology , Circular Dichroism , Molecular StructureABSTRACT
Excessive ammonium and phosphate in aquatic settings may produce major eutrophication. Adsorbents can be used to reduce the eutrophication of natural water bodies. In this study, a sustainable and efficient ceramic adsorbent (sludge/biomass ash ceramsite [SBC]) was prepared by using sludge and biomass ash with a weight ratio of 1:1; the sintering parameters were 1070°C for 15 min. The NH4 + -N and P adsorption capabilities were improved by utilizing 1 mol L-1 NaOH and 1.6 mol L-1 La(NO3 )3 ·6H2 O for modification. When the pH and duration were 7 and 1440 min, respectively, the maximum bending capacity of ammonia nitrogen and phosphorus was 3.2 and 2.1 mg g-1 at 308 K. The pseudo-second-order kinetic model better describes the adsorption dynamics of NH4 + -N and P, whereas the Langmuir model better describes the adsorption isotherm models of NH4 + -N and P. The adsorption mechanism of SBC-NaOH on NH4 + -N is ion exchange between Na+ and NH4 + , whereas the adsorption mechanism of SBC-La on phosphorus is ion exchange and La3+ adsorption. SBC combines efficient wastewater purification with the reuse of solid waste. The findings gave rise to the possibility of recycling ceramics as a plant fertilizer with a delayed release in the future. PRACTITIONER POINTS: New ceramsite was made from sludge and biomass ash. NH4 + -N (3.2 mg g-1 ) and P (2.1 mg g-1 ) were effectively adsorbed by ceramsite. The mechanism of NH4 + -N and P adsorption by ceramsite was studied. Absorbed ceramsite can be used as slow-release fertilizer in plant cultivation.
Subject(s)
Wastewater , Water Pollutants, Chemical , Sewage , Phosphorus , Nitrogen , Adsorption , Biomass , Fertilizers , Sodium Hydroxide , KineticsABSTRACT
Our previous work reported that galaxamide, a cyclopeptide extracted from the seaweed Galaxaura filamentosa, showed antiproliferative activity against HeLa cells by MTT assay. In this study, the growth-inhibitory effects of galaxamide in HeLa cells and xenograft mouse models were investigated. It was found galaxamide significantly inhibited cell growth, colony formation, migration, and invasion and induced cell apoptosis by inhibiting the Wnt signaling pathway in HeLa cells. RNA sequencing revealed that galaxamide regulated stemness by Wnt6 signaling pathway in HeLa cells. By analyzing The Cancer Genome Atlas database, Wnt6 was found to be negatively/positively correlated with stemness- and apoptosis-related genes in human cervical cancer. Cancer stem-like cells (CSCs) isolated and enriched from HeLa cells demonstrated elevated Wnt6 and ß-catenin genes compared with nonstem HeLa cells. After galaxamide treatment, CSCs showed abrogation of sphere-forming ability, along with inhibition of stemness-related and Wnt pathway genes. Galaxamide treatment was also accompanied by the induction of apoptosis in HeLa cells, which was consistent with the results in BALB/c nude mice. Our results provide evidence that suppression of stemness by downregulating the Wnt signaling pathway is the molecular mechanism by which galaxamide effectively inhibits cell growth and induces apoptosis in cervical cancer cells.
Subject(s)
Uterine Cervical Neoplasms , Wnt Signaling Pathway , Female , Humans , Animals , Mice , HeLa Cells , beta Catenin/genetics , Uterine Cervical Neoplasms/genetics , Mice, Nude , Peptides, Cyclic/chemistry , Peptides, Cyclic/pharmacology , Apoptosis , Cell Proliferation , Cell Line, TumorABSTRACT
A scalable electrochemical difunctionalization of gem-difluoroalkenes to structurally versatile difluoro motifs was achieved. This methodology features reagent-free conditions, good functional group tolerance, and a relatively broad substrate scope. Meanwhile, the electrolysis protocol is easy to handle, and the products show good regio- and chemoselectivity. The reaction mechanism was also preliminarily studied.
ABSTRACT
It is possible to achieve high-value utilization of solid wastes and lower the cost of mesoporous silica synthesis by synthesizing mesoporous silica from solid wastes. In this study, silica was extracted using the alkali fusion method using biomass ash as the starting material. Biomass ash based mesoporous silica was successfully prepared by hydrothermal method with silicon extract solution as silicon source. The optimum conditions for preparation were determined as follows: addition of cetyltrimethylammonium bromide was 0.45g, hydrothermal temperature was 120 °C, hydrothermal time was 24h. The prepared mesoporous silicon was systematically characterized, and the results showed that high surface area (495 m2/g) and ordered pore structure appeared in the synthesized mesoporous silica materials. The synthesized mesoporous silica showed excellent CO2 adsorption performance (0.749 mmol/g) at 25 °C and 1 bar. According to the calculation of adsorption isotherm and thermodynamics, non-linear Freundlich model can fit the adsorption isotherm better and the adsorption heat of mesoporous silica is less than 20 kJ/mol, which belongs to physical adsorption. After five cycles of CO2 adsorption, the adsorption property was still above 90%, and the CO2/N2 adsorption selectivity reached 396.6, showing good regeneration performance and adsorption selectivity. This research can provide a new possibility for the high-value exploitation of biomass ash and reducing the cost of synthetic mesoporous silica.
Subject(s)
Silicon Dioxide , Solid Waste , Silicon Dioxide/chemistry , Carbon Dioxide/chemistry , Silicon , Adsorption , BiomassABSTRACT
The rapid expansion of biomass power generation has resulted in a large amount of ash, which need to be treated urgently. The trace elements in ash also have environmental risks during treatment. Therefore, the essential characteristics and potential environmental risks of biomass ash generated by direct combustion of agricultural straw were studied. The leaching characteristics of elements, including major elements (Mg, K, Ca) and trace elements (V, Cr, Mn, Co, Ni, Cu, Zn, Cd, As, Pb and Ba), in fly ash and slag produced by biomass power plant were analyzed through the static leaching experiments of simulating the possible pH value of natural water in the laboratory. The results show that the trace elements are enriched in fly ash and slag, which may be related to the volatility of elements during combustion. And during the leaching test, the leaching concentration of major and trace elements in fly ash is higher than that in slag. Sequential chemical extraction is used to reveal the occurrence forms of trace elements in biomass ash. Except for residue, Mn, Co, Zn, Cd, and Pb in fly ash mainly exist in carbonate bound, V and As are Fe-Mn oxides bound, and Cr, Ni, Cu, and Ba are mainly organic matter bound. In the slag, Cd is mainly carbonate bound, Cu is mainly organic matter bound, while other elements are mainly Fe-Mn oxides bound. The Risk Assessment Code values calculated based on the existing forms of elements show that As and Cd in slag and Mn, Co, Pb and Cd in fly ash need special attention during utilization. The research results can provide reference for the management and utilization of biomass ash.