ABSTRACT
Garlic is a vegetable with numerous pro-health properties, showing high antioxidant capacity, and cytotoxicity for various malignant cells. The inhibition of cell proliferation by garlic is mainly attributed to the organosulfur compounds (OSCs), but it is far from obvious which constituents of garlic indeed participate in the antioxidant and cytotoxic action of garlic extracts. This study aimed to obtain insight into this question by examining the antioxidant activity and cytotoxicity of six OSCs and five phenolics present in garlic. Three common assays of antioxidant activity were employed (ABTSâ decolorization, DPPHâ decolorization, and FRAP). Cytotoxicity of both classes of compounds to PEO1 and SKOV-3 ovarian cancer cells, and MRC-5 fibroblasts was compared. Negligible antioxidant activities of the studied OSCs (alliin, allicin, S-allyl-D-cysteine, allyl sulfide, diallyl disulfide, and diallyl trisulfide) were observed, excluding the possibility of any significant contribution of these compounds to the total antioxidant capacity (TAC) of garlic extracts estimated by the commonly used reductive assays. Comparable cytotoxic activities of OSCs and phenolics (caffeic, p-coumaric, ferulic, gallic acids, and quercetin) indicate that both classes of compounds may contribute to the cytotoxic action of garlic.
Subject(s)
Allyl Compounds , Antioxidants , Disulfides , Garlic , Phenols , Plant Extracts , Sulfides , Sulfinic Acids , Garlic/chemistry , Humans , Antioxidants/pharmacology , Antioxidants/chemistry , Phenols/pharmacology , Phenols/chemistry , Disulfides/pharmacology , Disulfides/chemistry , Cell Line, Tumor , Plant Extracts/pharmacology , Plant Extracts/chemistry , Sulfinic Acids/pharmacology , Sulfinic Acids/chemistry , Sulfides/pharmacology , Sulfides/chemistry , Allyl Compounds/pharmacology , Allyl Compounds/chemistry , Sulfur Compounds/pharmacology , Sulfur Compounds/chemistry , Cysteine/analogs & derivatives , Cysteine/chemistry , Cysteine/pharmacology , Cell Survival/drug effects , Cell Proliferation/drug effects , Fibroblasts/drug effects , Fibroblasts/metabolismABSTRACT
Volatile sulfur compounds (VSCs) significantly influence food flavor and garner considerable attention in flavor research due to their low sensory thresholds, diverse odor attributes, and high reactivity. Extensive research studies have explored VSC formation through thermal processes such as the Maillard reaction, thermal pyrolysis, oxidation, and enzymatic reactions. However, understanding of the specific reaction mechanisms and processes remains limited. This is due to the dispersed nature of existing studies, the undefined intermediates involved, and the complexity of the matrices and processing conditions. Given these limitations, the authors have shifted their focus from foods to sulfides. The structure, source, and chemical characteristics of common precursors (sulfur-containing amino acids and derivatives, thiamine, thioglucoside, and lentinic acid) and their corresponding reactive intermediates (hydrogen sulfide, thiol, alkyl sulfide, alkyl sulfenic acid, and thial) are provided, and the degradation mechanisms, reaction rules, and matrix conditions are summarized based on their chemical characteristics. Additionally, the VSC formation processes in several typical foods during processing are elucidated, adhering to these identified rules. This article provides a comprehensive overview of VSCs, from precursors and intermediates to end products, and is crucial for understanding the mechanisms behind VSC formation and managing the flavor qualities of processed foods.
Subject(s)
Food Handling , Hot Temperature , Odorants , Sulfur Compounds , Sulfur Compounds/chemistry , Odorants/analysis , Food Handling/methods , Volatile Organic Compounds/chemistry , Taste , Maillard Reaction , Food AnalysisABSTRACT
With increasingly stringent emission limits on sulfur and sulfur-containing substances, the reduction and removal of sulfur compounds from fuels has become an urgent task. Emissions of sulfur-containing compounds pose a significant threat to the environment and human health. Ionic liquids (ILs) have attracted much attention in recent years as green solvents and functional materials, and their unique properties make them useful alternatives to conventional desulfurization organic solvents. This paper reviews the advantages and disadvantages of traditional desulfurization technologies such as hydrodesulfurization, oxidative desulfurization, biological desulfurization, adsorptive desulfurization, extractive desulfurization, etc. It focuses on the synthesis of ionic liquids and their applications in oxidative desulfurization, extractive desulfurization, extractive oxidative desulfurization, and catalytic oxidative desulfurization, and it analyzes the problems of ionic liquids that need to be solved urgently in desulfurization, looking forward to the development of sulfuric compounds as a kind of new and emerging green solvent in the field of desulfurization.
Subject(s)
Green Chemistry Technology , Ionic Liquids , Ionic Liquids/chemistry , Green Chemistry Technology/methods , Sulfur/chemistry , Sulfur Compounds/chemistry , Oxidation-ReductionABSTRACT
The registration of novel pesticides that are subsequently banned because of their unexpected negative effects on non-target species can have a huge environmental impact. Therefore, the pre-emptive evaluation of the potential effects of new compounds is essential. To this aim both lethal and sublethal effects should be assessed in a realistic scenario including the other stressors that can interact with pesticides. However, laboratory studies addressing such interactive effects are rare, while standardized laboratory-based protocols focus on lethal effects and not on sub-lethal effects. We propose to assess both lethal and sublethal effects in a multifactorial context including the other stressors affecting the non-target species. We tested this approach by studying the impact on honey bees of the insecticide sulfoxaflor in combination with a common parasite, a sub-optimal temperature and food deprivation. We studied the survival and the transcriptome of honey bees, to assess both the lethal and the potential sublethal effects of the insecticide, respectively. With this method we show that a field realistic concentration of sulfoxaflor in food does not affect the survival of honey bees; however, the significant impact on some key genes indicates that sublethal effects are possible in a realistically complex scenario. Moreover, our results demonstrate the feasibility and reliability of a novel approach to hazard assessment considering the interactive effects of pesticides. We anticipate our approach to be a starting point for a paradigm shift in toxicology: from an unifactorial, mortality-centered assessment to a multifactorial, comprehensive approach. This is something of the utmost importance to preserve pollination, thus contributing to the sustainability of our food production system.
Subject(s)
Pesticides , Bees/drug effects , Bees/physiology , Animals , Pesticides/toxicity , Insecticides/toxicity , Sulfur Compounds/toxicity , Pyridines/toxicity , Transcriptome/drug effectsABSTRACT
Growing evidence indicates that the intake of trans fatty acids (TFAs) increases the risk of numerous diseases, such as cardiovascular diseases. Recently, our group found that certain natural sulfur compounds (allyl isothiocyanate [AITC] and diallyl disulfide [DADS]) promote cis to trans isomerization of fatty acid esters during heat treatment. However, little information is available on the fatty acid isomerization with them. In this study, we investigated the effects of oxygen and α-tocopherol (antioxidant) on isomerization of oleic acid (18:1) methyl ester (OA-ME) in the presence of AITC and DADS. Furthermore, the effect of the simultaneous use of AITC and DADS was evaluated. Our results indicate that oxygen enhances the AITC-induced trans isomerization, and DADS was found to promote trans isomerization but inhibit AITC-induced trans isomerization during heating. Both AITC- and DADS-induced trans isomerization were inhibited by α-tocopherol. These results indicate that the trans isomerization of fatty acids induced by sulfur compounds can be controlled by devising a cooking process and the food ingredients used together.
Subject(s)
Disulfides , Isothiocyanates , Oleic Acids , alpha-Tocopherol , Isomerism , alpha-Tocopherol/chemistry , Disulfides/chemistry , Oleic Acids/chemistry , Isothiocyanates/chemistry , Allyl Compounds/chemistry , Oxygen/chemistry , Antioxidants/chemistry , Hot Temperature , Sulfur Compounds/chemistry , Cooking , Oleic Acid/chemistry , Trans Fatty Acids/chemistry , Esters/chemistry , Stereoisomerism , Cysteine/analogs & derivativesABSTRACT
One of the greatest challenges encountered by enteric pathogens is responding to rapid changes of nutrient availability in host. However, the mechanisms by which pathogens sense gastrointestinal signals and exploit available host nutrients for proliferation remain largely unknown. Here, we identified a two-component system in Vibrio parahaemolyticus, TtrRS, which senses environmental tetrathionate and subsequently activates the transcription of the ttrRS-ttrBCA-tsdBA gene cluster to promote V. parahaemolyticus colonization of adult mice. We demonstrated that TsdBA confers the ability of thiosulfate oxidation to produce tetrathionate which is sensed by TtrRS. TtrRS autoregulates and directly activates the transcription of the ttrBCA and tsdBA gene clusters. Activated TtrBCA promotes bacterial growth under micro-aerobic conditions by inducing the reduction of both tetrathionate and thiosulfate. TtrBCA and TsdBA activation by TtrRS is important for V. parahaemolyticus to colonize adult mice. Therefore, TtrRS and their target genes constitute a tetrathionate-responsive genetic circuit to exploit the host available sulfur compounds, which further contributes to the intestinal colonization of V. parahaemolyticus.
Subject(s)
Bacterial Proteins , Vibrio Infections , Vibrio parahaemolyticus , Vibrio parahaemolyticus/metabolism , Vibrio parahaemolyticus/genetics , Animals , Mice , Bacterial Proteins/metabolism , Bacterial Proteins/genetics , Sulfur Compounds/metabolism , Gene Expression Regulation, Bacterial , Female , Mice, Inbred C57BLABSTRACT
OBJECTIVE: To assess the efficacy of Phyllanthus emblica extract in alleviating halitosis and reducing the inflammatory response to halitosis-related bacteria. METHODOLOGY: This investigation, using Phyllanthus emblica fruit extract (PE), involved four aspects. First, we evaluated the effect on growth and aggregation of halitosis-related bacteria, including Fusobacterium nucleatum, Porphyromonas gingivalis, and Solobacterium moorei, using a microdilution assay and scanning electron microscopy. Second, volatile sulfur compound (VSC) levels were measured on individuals with halitosis in randomized short-term (26 participants) and double-blind randomized long-term trials (18 participants in each group) after rinsing with PE for 3, 6, and 12 h, and 28 days. Third, we analyzed pro-inflammatory cytokine expression in TR146 cells using quantitative real-time PCR and enzyme-linked immunosorbent assays. Lastly, we assessed pro-inflammatory cytokine secretion and Toll-like receptor (TLR) 2 mRNA expression via the same experimental methods in a three-dimensional oral mucosal epithelial model (3D OMEM). RESULTS: PE extract dose-dependently inhibited the growth of F. nucleatum (50% inhibition concentration [IC50]=0.079%), P. gingivalis (IC50=0.65%), and S. moorei (IC50=0.07%) and effectively prevented bacterial aggregation. Furthermore, VSC contents decreased significantly at 3, 6, and 12 h after rinsing with 5% PE compared with those in the control. Long-term use of mouthwash containing 5% PE for 28 days led to a significant decrease in VSC contents. PE attenuated the F. nucleatum- or P. gingivalis-stimulated mRNA expression and protein release of interleukin (IL)-6 and IL-8 in TR146 cells. It also suppressed IL-8 and prostaglandin E2 secretion and TLR2 mRNA expression in F. nucleatum-induced OMEMs. CONCLUSION: Our findings support the use of PE in oral care products to alleviate halitosis and it may reduce inflammation.
Subject(s)
Cytokines , Enzyme-Linked Immunosorbent Assay , Fusobacterium nucleatum , Halitosis , Microscopy, Electron, Scanning , Phyllanthus emblica , Plant Extracts , Porphyromonas gingivalis , Real-Time Polymerase Chain Reaction , Phyllanthus emblica/chemistry , Halitosis/drug therapy , Halitosis/microbiology , Humans , Plant Extracts/pharmacology , Double-Blind Method , Fusobacterium nucleatum/drug effects , Porphyromonas gingivalis/drug effects , Female , Time Factors , Male , Treatment Outcome , Adult , Young Adult , Toll-Like Receptor 2/drug effects , Fruit/chemistry , Statistics, Nonparametric , Mouth Mucosa/drug effects , Mouth Mucosa/microbiology , Analysis of Variance , Sulfur Compounds/pharmacology , Sulfur Compounds/analysisABSTRACT
The tarnished plant bug, (TPB) Lygus lineolaris Palisot de Beauvois (Hemiptera: Miridae) is a key pest of cotton in the midsouth region and some areas of the eastern United States. Its control methods have been solely based on chemical insecticides which has contributed to insecticidal resistance and shortened residual periods for control of this insect pest. This study was conducted over a two-year period and examined the efficacy and residual effect of four commercial insecticides including lambda-cyhalothrin (pyrethroid), acephate (organophosphate), imidacloprid (neonicotinoid), and sulfoxaflor (sulfoxamine). The effectiveness and residual effects of these insecticides were determined by application on cotton field plots on four different dates during each season using three different concentrations (high: highest labeled commercial dose (CD), medium: 1/10 of the CD, low: 1/100 of the CD) on field cotton plots. Four groups of cotton leaves were randomly pulled from each treated plot and control 0-, 2-, 4-, 7-, and 9-days post treatment (DPT) and exposed to a lab colony of TPB adults. One extra leaf sample/ plot/ spray /DPT interval (0-2-4-7-9-11) during 2016 was randomly collected from the high concentration plots and sent to Mississippi State Chemical Laboratory for residual analysis. Mortality of TPB adults was greatest for those placed on leaves sprayed with the organophosphate insecticide with mortalities (%) of 81.7±23.4 and 63.3±28.8 (SE) 1-day after exposure (DAE) on leaves 0-DPT with the high concentration for 2016 and 2017, respectively, reaching 94.5±9.5 and 95.4±7.6 6-DAE each year. Mortality to all insecticides continued until 9 and 4-DPT for high and medium concentrations, respectively. However, organophosphate (39.4±28.6) and pyrethroid (24.4±9.9) exhibited higher mortality than sulfoxamine (10.6±6.6) and the neonicotinoid (4.0±1.5) 7-DAE on 9-DPT leaves with the high concentration. Based on our results using the current assay procedure, TPB adults were significantly more susceptible to contact than systemic insecticides and due to its residual effect, organophosphate could kill over 80% of the TPB population 7-DPT.
Subject(s)
Gossypium , Insecticides , Neonicotinoids , Nitriles , Nitro Compounds , Phosphoramides , Pyrethrins , Insecticides/pharmacology , Gossypium/parasitology , Animals , Pyrethrins/pharmacology , Neonicotinoids/pharmacology , Mississippi , Nitriles/pharmacology , Nitro Compounds/pharmacology , Insect Control/methods , Heteroptera/drug effects , Imidazoles/pharmacology , Hemiptera/drug effects , Organothiophosphorus Compounds , Pyridines , Sulfur CompoundsABSTRACT
BACKGROUND: PDE10A inhibition represents a potential mechanism for treating schizophrenia. PDE10A inhibitors increase cyclic nucleotides in striatal neurons, thereby mimicking the effects of dopamine receptor D2 antagonists and D1 agonists. We evaluated the PDE10A inhibitor MK-8189 for treating schizophrenia. METHODS: Randomized, double-blind, placebo and active-controlled, phase 2a, multicenter, inpatient trial in adults experiencing an acute episode of schizophrenia. Participants were randomized 2:2:1 to once-daily MK-8189 12 mg, placebo, or risperidone 6 mg (active control) for 4-weeks. The primary outcome was change-from-baseline in total score on the Positive and Negative Syndrome Scale (PANSS) at 4 weeks. RESULTS: The number of treated participants was 90 for MK-8189, 89 for placebo, and 45 for risperidone. MK-8189 demonstrated a trend towards improvement versus placebo for change-from-baseline in PANSS total score after 4 weeks (difference = -4.7 [95 % CI: -9.8,0.5], P = 0.074). The active control risperidone was superior to placebo on PANNS total score (difference = -7.3 [95 % CI: -14.0,-0.6], P = 0.033), demonstrating assay sensitivity, while MK-8189 and risperidone did not significantly differ (difference = 2.6 [95 % CI: -4.0,9.2], P = 0.440). MK-8189 had a nominally significant effect on PANSS positive subscale score compared to placebo (difference = -2.2 [95 % CI: -3.8,-0.5], P = 0.011). Discontinuation of MK-8189 treatment due to an adverse event was low (<10 %). Extrapyramidal symptoms occurred with MK-8189 but were mostly mild and transient. Compared with placebo, MK-8189 reduced body weight while risperidone increased weight. CONCLUSIONS: These findings suggest that PDE10A inhibition may produce antipsychotic effects and associated weight loss and that further trials with PDE10A inhibitors are warranted. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT03055338.
Subject(s)
Antipsychotic Agents , Phosphoric Diester Hydrolases , Pyrimidines , Risperidone , Schizophrenia , Sulfur Compounds , Adult , Female , Humans , Male , Middle Aged , Young Adult , Acute Disease , Antipsychotic Agents/pharmacology , Antipsychotic Agents/adverse effects , Antipsychotic Agents/administration & dosage , Double-Blind Method , Outcome Assessment, Health Care , Phosphodiesterase Inhibitors/adverse effects , Phosphodiesterase Inhibitors/pharmacology , Phosphodiesterase Inhibitors/therapeutic use , Phosphoric Diester Hydrolases/metabolism , Proof of Concept Study , Pyrimidines/adverse effects , Pyrimidines/pharmacology , Pyrimidines/therapeutic use , Risperidone/pharmacology , Risperidone/adverse effects , Risperidone/administration & dosage , Schizophrenia/drug therapy , Sulfur Compounds/adverse effects , Sulfur Compounds/pharmacology , Sulfur Compounds/therapeutic useABSTRACT
The inherent structural properties of enzymes are critical in defining catalytic function. Often, studies to evaluate the relationship between structure and function are limited to only one defined structural element. The two-component flavin-dependent desulfonase family of enzymes involved in bacterial sulfur acquisition utilize a comprehensive range of structural features to carry out the desulfonation of organosulfur compounds. These metabolically essential two-component FMN-dependent desulfonase systems have been proposed to utilize oligomeric changes, protein-protein interactions for flavin transfer, and common mechanistic steps for carbon-sulfur bond cleavage. This review is focused on our current functional and structural understanding of two-component FMN-dependent desulfonase systems from multiple bacterial sources. Mechanistic and structural comparisons from recent independent studies provide fresh insights into the overall functional properties of these systems and note areas in need of further investigation. The review acknowledges current studies focused on evaluating the structural properties of these enzymes in relationship to their distinct catalytic function. The role of these enzymes in maintaining adequate sulfur levels, coupled with the conserved nature of these enzymes in diverse bacteria, underscore the importance in understanding the functional and structural nuances of these systems.
Subject(s)
Bacterial Proteins , Bacterial Proteins/chemistry , Bacterial Proteins/metabolism , Bacteria/enzymology , Sulfur Compounds/metabolism , Sulfur Compounds/chemistry , Hydrolases/chemistry , Hydrolases/metabolism , Flavin Mononucleotide/metabolism , Flavin Mononucleotide/chemistry , Sulfur/metabolism , Sulfur/chemistry , Flavins/metabolism , Flavins/chemistry , Structure-Activity Relationship , Carbon/metabolism , Carbon/chemistryABSTRACT
BACKGROUND: Chronic kidney disease (CKD) directly affects oral health. Yet data about halitosis in young CKD patients and the impact of dental prophylaxis is limited. Therefore, as part of this randomized clinical trial, halitosis in young CKD patients undergoing intensive or standard oral preventive procedures was to be explored. METHODS: Three volatile sulfur compounds (hydrogen sulfide, methyl mercaptan and dimethyl sulfide) were measured in 30 young patients with CKD (mean age 14.2 years; 16 males, 14 females). Breath samples were taken after 3 and 6 months and analyzed with selective gas chromatography (OralChroma). Tongue coating (Winkel Index) and clinical indices to determine local inflammation or oral hygiene (Papillary Bleeding Index and Quigley-Hein Index) were assessed. Within an extended anamnesis, patients and their mothers and nurses were questioned about the perceived halitosis. Corresponding quotes were noted verbatim. Patients were randomized to either intensive need-related oral health care measures (oral preventative program, OPP) or a one-stage standard prevention (treatment as usual, TAU). RESULTS: While there were no differences in volatile sulfur compound levels between TAU and OPP at the three time points of measurements (p > 0.05), there was a tendency towards a reduction in dimethyl sulfide and hydrogen sulfide of affected patients within the OPP group over time. Looking at potential differences between both groups with regard to tongue coating, significant differences were observed between baseline and 3 months after study start in the OPP group, and between baseline and 6 months after study start in the TAU group (p < 0.05). The burden of halitosis was frequently reported by patients' mothers and nurses. CONCLUSIONS: Young CKD patients regularly suffered from halitosis and dimethyl sulfide was its main source. Preventive measures mainly resulted in a reduction of tongue coating. TRIAL REGISTRATION: The German Clinical Trial Register (# DRKS00010580).
Subject(s)
Halitosis , Renal Insufficiency, Chronic , Humans , Halitosis/etiology , Halitosis/prevention & control , Female , Male , Adolescent , Renal Insufficiency, Chronic/complications , Breath Tests/methods , Child , Oral Hygiene , Sulfur Compounds/analysis , Chromatography, Gas/methods , Hydrogen SulfideABSTRACT
OBJECTIVES: The purpose of this systemic review and meta-analysis was to explore the association between halitosis and periodontitis in observational studies. MATERIALS AND METHODS: A systematic search covered PubMed, Web of Science, Embase, Scopus, and Cochrane Library until August 18, 2023. Nine observational studies (585 cases, 1591 controls) were analyzed using Stata 17, with odds ratios (ORs) and 95% confidence intervals (CIs). Subgroup analyses considered halitosis assessment methods. RESULTS: The review found a positive association between halitosis and periodontitis. Significant differences were observed with organoleptic test (OR = 4.05, 95% CI: 1.76, 9.30, p < 0.01) and volatile sulfur compound readings (OR = 4.52, 95% CI: 1.89, 10.83, p < 0.01). CONCLUSIONS: A positive association was observed between halitosis and periodontitis, supported by significant differences in both organoleptic and volatile sulfur compound readings. However, conclusive findings are limited by statistical heterogeneity, emphasizing the need for additional research. CLINICAL RELEVANCE: Understanding the halitosis and periodontitis association is clinically significant, informing potential interventions for improved oral health. Further research is vital to refine understanding and guide effective clinical strategies, acknowledging the limitations in current findings.
Subject(s)
Halitosis , Periodontitis , Halitosis/etiology , Humans , Periodontitis/complications , Sulfur Compounds/analysis , Observational Studies as TopicABSTRACT
Trace palladium in synthetic materials can be rapidly and inexpensively semiquantified by a catalysis-based fluorometric method that converts resorufin allyl ether to resorufin. However, whether sulfur compounds would interfere with this method has not been systematically studied. Herein, we show that although thiourea in solution interferes with quantification, sulfide, thiol, and thiocarbamate do not. The fluorometric method can also detect palladium bound to sulfur-based scavenger resin and outperform inductively coupled plasma mass spectrometry for detecting trace palladium in ibuprofen.
Subject(s)
Fluorometry , Ibuprofen , Palladium , Palladium/chemistry , Ibuprofen/chemistry , Ibuprofen/analysis , Catalysis , Fluorometry/methods , Molecular Structure , Sulfur Compounds/chemistry , Sulfur Compounds/analysisABSTRACT
Periodontosis is the most common clinical disease in adult dogs, which is mainly caused by plaque accumulation and seriously endangers the oral health of dogs and even cause kidney, myocardial, and liver problems in severe cases. The aim of this study was to determine the clinical efficacy of dental chew (Cature Brushing Treats product) with mechanical and chemical properties in beagles. The dogs in the experimental group were fed with a dental chew twice a day after meals; The control group had no treatment. Dental plaque was evaluated on the 14th day and 29th day, respectively. The concentration of volatile sulfur compounds (VSC) in the breath and dental calculus were also evaluated on the 29th day. The results showed that there was no significant difference in the indexes of dental plaque on the 14th day. While they had significantly reduced accumulation of plaque (37.63%), calculus (37.61%), and VSC concentration (81.08%) compared to when receiving no chew on the 29th day.
Subject(s)
Dental Calculus , Dental Plaque , Dog Diseases , Halitosis , Animals , Dogs , Halitosis/veterinary , Halitosis/prevention & control , Dental Plaque/veterinary , Dental Plaque/prevention & control , Dental Calculus/veterinary , Dental Calculus/chemistry , Dental Calculus/prevention & control , Male , Female , Sulfur Compounds/analysisABSTRACT
Targeted radionuclide therapy, in which radiopharmaceuticals deliver potent radionuclides to tumours for localized irradiation, has addressed unmet clinical needs and improved outcomes for patients with cancer1-4. A therapeutic radiopharmaceutical must achieve both sustainable tumour targeting and fast clearance from healthy tissue, which remains a major challenge5,6. A targeted ligation strategy that selectively fixes the radiopharmaceutical to the target protein in the tumour would be an ideal solution. Here we installed a sulfur (VI) fluoride exchange (SuFEx) chemistry-based linker on radiopharmaceuticals to prevent excessively fast tumour clearance. When the engineered radiopharmaceutical binds to the tumour-specific protein, the system undergoes a binding-to-ligation transition and readily conjugates to the tyrosine residues through the 'click' SuFEx reaction. The application of this strategy to a fibroblast activation protein (FAP) inhibitor (FAPI) triggered more than 80% covalent binding to the protein and almost no dissociation for six days. In mice, SuFEx-engineered FAPI showed 257% greater tumour uptake than did the original FAPI, and increased tumour retention by 13-fold. The uptake in healthy tissues was rapidly cleared. In a pilot imaging study, this strategy identified more tumour lesions in patients with cancer than did other methods. SuFEx-engineered FAPI also successfully achieved targeted ß- and α-radionuclide therapy, causing nearly complete tumour regression in mice. Another SuFEx-engineered radioligand that targets prostate-specific membrane antigen (PSMA) also showed enhanced therapeutic efficacy. Considering the broad scope of proteins that can potentially be ligated to SuFEx warheads, it might be possible to adapt this strategy to other cancer targets.
Subject(s)
Molecular Targeted Therapy , Prostatic Neoplasms , Radioisotopes , Radiopharmaceuticals , Animals , Humans , Male , Mice , Antigens, Surface/chemistry , Antigens, Surface/metabolism , Cell Line, Tumor , Fluorides/chemistry , Fluorides/metabolism , Glutamate Carboxypeptidase II/chemistry , Glutamate Carboxypeptidase II/metabolism , Ligands , Membrane Proteins/metabolism , Membrane Proteins/chemistry , Molecular Targeted Therapy/methods , Pilot Projects , Prostatic Neoplasms/metabolism , Prostatic Neoplasms/radiotherapy , Radioisotopes/therapeutic use , Radiopharmaceuticals/chemistry , Radiopharmaceuticals/therapeutic use , Radiopharmaceuticals/metabolism , Radiopharmaceuticals/pharmacokinetics , Sulfur Compounds/chemistry , Sulfur Compounds/metabolism , Tyrosine/metabolism , Tyrosine/chemistry , Xenograft Model Antitumor AssaysABSTRACT
Sulfur-containing natural products possess a variety of biological functions including antitumor, antibacterial, anti-inflammatory and antiviral activities. In this study, four previously undescribed sulfur-containing compounds asperteretals L and M, terreins A and B, together with 17 known compounds were obtained from a culture of marine fungus A. terreus supplemented with inorganic sulfur source Na2SO4. Their planar structures and absolute configurations were elucidated by NMR, HRESIMS, and ECD experiments. The in vitro cytotoxicities of compounds 1-21 against HCT-116 and Caco-2 were evaluated by SRB assay. Asperteretal M (2) exhibited activity against HCT-116 with the IC50 value at 30µM. The antiproliferative effect of asperteretal M was confirmed by colony formation assay and cell death staining. Furthermore, the preliminary study on the anti-colon cancer mechanism of asperteretal M was performed by RNA-seq analysis. Western blotting validated that asperteretal M significantly decreased the expression of cell-cycle regulatory proteins CDK1, CDK4, and PCNA in a concentration-dependent manner.
Subject(s)
Antineoplastic Agents , Aspergillus , Sulfur Compounds , Humans , Aspergillus/chemistry , Molecular Structure , HCT116 Cells , Sulfur Compounds/pharmacology , Sulfur Compounds/isolation & purification , Antineoplastic Agents/pharmacology , Antineoplastic Agents/isolation & purification , Caco-2 Cells , Colonic Neoplasms/drug therapyABSTRACT
Sulfoxaflor is a widely used fourth-generation neonicotinoid pesticide, which has been detected in biological and environmental samples. Sulfoxaflor can potentially be exposed to humans via the food chain, thus understanding its toxic effects and enantioselective bioaccumulation is crucial. In this study, toxicokinetics, bioaccumulation, tissue distribution and enantiomeric profiles of sulfoxaflor in rats were investigated through single oral exposure and 28-days continuous exposure experiment. Sulfoxaflor mainly accumulated in liver and kidney, and the (-)-2R,3R-sulfoxaflor and (-)-2S,3R-sulfoxaflor had higher enrichment than their enantiomers in rats. The toxicological effects were evaluated after 28-days exposure. Slight inflammation in liver and kidney were observed by histopathology. Sphingolipid, amino acid, and vitamin B6 metabolism pathways were significantly disturbed in metabonomics analysis. These toxicities were in compliance with dose-dependent effects. These results improve understanding of enantioselective bioaccumulation and the potential health risk of sulfoxaflor.
Subject(s)
Liver , Sulfur Compounds , Animals , Rats , Sulfur Compounds/toxicity , Sulfur Compounds/metabolism , Liver/metabolism , Liver/drug effects , Male , Stereoisomerism , Kidney/metabolism , Kidney/drug effects , Bioaccumulation , Pyridines/toxicity , Pyridines/metabolism , Tissue Distribution , Neonicotinoids/toxicity , Neonicotinoids/metabolism , Rats, Sprague-Dawley , Insecticides/toxicity , Pesticides/toxicity , Pesticides/metabolismABSTRACT
In recent years, the malodorous gases generated by sewage treatment plants have gradually received widespread attention due to their sensory stimulation and health hazards. The emission concentration, sensory evaluation and health risk assessment of volatile sulfur compounds (VSCs) were all explored in two municipal wastewater treatment plants (WWTPs) with oxidation ditch and anaerobic/oxic treatment process, respectively. The VSCs concentration showed the highest amount in the primary treatment unit in both the two WWTPs (73.3% in Plant A and 93.0% in Plant B), while the H2S took the main role in the composition of VSCs. However, H2S took a larger percentage in Plant A (84.5% â¼ 87.0%) rather than Plant B (61.2% â¼ 83.5%), which may be due to the different operating conditions and sludge properties in different treatment process. Besides, H2S also gained the first rank in the sensory evaluation and health risk assessment, which may cause considerable sensory irritation and health risk to workers and surrounding residents. Furthermore, the influencing factor analyses of VSCs emission showed that the temperature of water and air, ORP of sludge made the greatest effect on VSCs release. This study provides theoretical and data support for the research of VSCs emission control in WWTPs.
Subject(s)
Sulfur Compounds , Waste Disposal, Fluid , Wastewater , Risk Assessment , Wastewater/chemistry , Sulfur Compounds/analysis , Air Pollutants/analysis , Environmental Monitoring/methods , Sewage , HumansABSTRACT
Although sulfur cycling in acid mine drainage (AMD)-contaminated rice paddy soils is critical to understanding and mitigating the environmental consequences of AMD, potential sources and transformations of organosulfur compounds in such soils are poorly understood. We used sulfur K-edge X-ray absorption near edge structure (XANES) spectroscopy to quantify organosulfur compounds in paddy soils from five AMD-contaminated sites and one AMD-uncontaminated reference site near the Dabaoshan sulfide mining area in South China. We also determined the sulfur stable isotope compositions of water-soluble sulfate (δ34SWS), adsorbed sulfate (δ34SAS), fulvic acid sulfur (δ34SFAS), and humic acid sulfur (δ34SHAS) in these samples. Organosulfate was the dominant functional group in humic acid sulfur (HAS) in both AMD-contaminated (46%) and AMD-uncontaminated paddy soils (42%). Thiol/organic monosulfide contributed a significantly lower proportion of HAS in AMD-contaminated paddy soils (8%) compared to that in AMD-uncontaminated paddy soils (21%). Within contaminated soils, the concentration of thiol/organic monosulfide was positively correlated with cation exchange capacity (CEC), moisture content (MC), and total Fe (TFe). δ34SFAS ranged from -6.3 to 2.7, similar to δ34SWS (-6.9 to 8.9), indicating that fulvic acid sulfur (FAS) was mainly derived from biogenic S-bearing organic compounds produced by assimilatory sulfate reduction. δ34SHAS (-11.0 to -1.6) were more negative compared to δ34SWS, indicating that dissimilatory sulfate reduction and abiotic sulfurization of organic matter were the main processes in the formation of HAS.
Subject(s)
Mining , Oryza , Soil Pollutants , Soil , Soil/chemistry , Oryza/chemistry , Humic Substances , Sulfur , Sulfur CompoundsABSTRACT
Antarctic seaweeds are vital components of polar marine ecosystems, playing a crucial role in nutrient cycling and supporting diverse life forms. The sulfur content in these organisms is particularly interesting due to its implication in biogeochemical processes and potential impacts on local and global environmental systems. In this study, we present a comprehensive characterization of seaweed collected in the Antarctic in terms of their total sulfur content and its distribution among different classes of species, including thiols, using various methods and high-sensitivity techniques. The data presented in this paper are unprecedented in the scientific literature. These methods allowed for the determination of total sulfur content and the distribution of sulfur compounds in different fractions, such as water-soluble and proteins, as well as the speciation of sulfur compounds in these fractions, providing valuable insights into the chemical composition of these unique marine organisms. Our results revealed that the total sulfur concentration in Antarctic seaweeds varied widely across different species, ranging from 5.5 to 56 g kg-1 dry weight. Furthermore, our investigation into the sulfur speciation revealed the presence of various sulfur compounds, including sulfate, and some thiols, which were quantified in all ten seaweed species evaluated. The concentration of these individual sulfur species also displayed considerable variability among the studied seaweeds. This study provides the first in-depth examination of total sulfur content and sulfur speciation in brown and red Antarctic seaweeds.