Priming avocado with sodium hydrosulfide prior to frost conditions induces the expression of genes involved in protection and stress responses.

Priming plants with chemical agents has been extensively investigated as a means for improving their tolerance to many biotic and abiotic stresses. Earlier, we showed that priming young avocado (Persea americana Mill cv. 'Hass') trees with sodium hydrosulfide (NaHS), a donor of hydrogen sulfide, improves the response of photosynthesis to simulated frost (cold followed by high light) conditions. In the current study, we performed a transcriptome analysis to gain insight into the molecular response of avocado 'Hass' leaves to frost, with or without NaHS priming. The analysis revealed 2144 (down-regulated) and 2064 (up-regulated) differentially expressed genes (DEGs) common to both non-primed and primed trees. Non-primed trees had 697 (down) and 559 (up) unique DEGs, while primed trees exhibited 1395 (down) and 1385 (up) unique DEGs. We focus on changes in the expression patterns of genes encoding proteins involved in photosynthesis, carbon cycle, protective functions, biosynthesis of isoprenoids and abscisic acid (ABA), as well as ABA-regulated genes. Notably, the differential expression results depict the enhanced response of primed trees to the frost and highlight gene expression changes unique to primed trees. Amongst these are up-regulated genes encoding pathogenesis-related proteins, heat shock proteins, enzymes for ABA metabolism, and ABA-induced transcription factors. Extending the priming experiments to field conditions, which showed a benefit to the physiology of trees following chilling, suggests that it can be a possible means to improve trees' response to cold stress under natural winter conditions.

Industrial Distillation Fractions of Garlic Essential Oil, Design, Synthesis, and Antifungal Activity Evaluation of Aliphatic Substituted Trisulfide Derivatives.

Garlic oil has a wide range of biological activities, and its broad-spectrum activity against phytopathogenic fungi still has the potential to be explored. In this study, enzymatic treatment of garlic resulted in an increase of approximately 50 % in the yield of essential oil, a feasible GC-MS analytical program for garlic oil was provided. Vacuum fractionation of the volatile oil and determination of its inhibitory activity against 10 fungi demonstrated that garlic oil has good antifungal activity. The antifungal activity levels were ranked as diallyl trisulfide (S-3)>diallyl disulfide (S-2)>diallyl monosulfide (S-1), with an EC50 value of S-3 against Botrytis cinerea reached 8.16 mg/L. Following the structural modification of compound S-3, a series of derivatives, including compounds S-4~7, were synthesized and screened for their antifungal activity. The findings unequivocally demonstrated that the compound dimethyl trisulfide (S-4) exhibited exceptional antifungal activity. The EC50 of S-4 against Sclerotinia sclerotiorum reached 6.83 mg/L. SEM, In vivo experiments, and changes in mycelial nucleic acids, soluble proteins and soluble sugar leakage further confirmed its antifungal activity. The study indicated that the trisulfide bond structure was the key to good antifungal activity, which can be developed into a new type of green plant-derived fungicide for plant protection.

The influence of thioether-substituted ligands in dicopper(II) complexes: Enhancing oxidation and biological activities.

This paper describes the synthesis, structural analysis, as well as the magnetic and spectroscopic characterizations of three new dicopper(II) complexes with dinucleating phenol-based ligands containing different thioether donor substituents: aromatic (1), aliphatic (2) or thiophene (3). Temperature-dependent magnetometry reveals the presence of antiferromagnetic coupling for 1 and 3 (J = -2.27 cm-1 and -5.01 cm-1, respectively, H = -2JS1S2) and ferromagnetic coupling for 2 (J = 5.72 cm-1). Broken symmetry DFT calculations attribute this behavior to a major contribution from the dz2 orbitals for 1 and 3, and from the dx2-y2 orbitals for 2, along with the p orbitals of the oxygens. The bioinspired catalytic activities of these complexes related to catechol oxidase were studied using 3,5-di-tert-butylcatechol as substrate. The order of catalytic rates for the substrate oxidation follows the trend 1 > 2 > 3 with kcat of (90.79 ± 2.90) × 10-3 for 1, (64.21 ± 0.99) × 10-3 for 2 and (14.20 ± 0.32) × 10-3 s-1 for 3. The complexes also cleave DNA through an oxidative mechanism with minor-groove preference, as indicated by experimental and molecular docking assays. Antimicrobial potential of these highly active complexes has shown that 3 inhibits both Staphylococcus aureus bacterium and Epidermophyton floccosum fungus. Notably, the complexes were found to be nontoxic to normal cells but exhibited cytotoxicity against epidermoid carcinoma cells, surpassing the activity of the metallodrug cisplatin. This research shows the multifaceted properties of these complexes, making them promising candidates for various applications in catalysis, nucleic acids research, and antimicrobial activities.

Combating infections from drug-resistant bacteria: Unleashing synergistic broad-spectrum antibacterial power with high-entropy MXene/CDs.

The growing resistance of bacteria to antibiotics has posed challenges in treating associated bacterial infections, while the development of multi-model antibacterial strategies could efficient sterilization to prevent drug resistance. High-entropy MXene has emerged as a promising candidate for antibacterial synergy with inherent photothermal and photodynamic properties. Herein, a high-entropy nanomaterial of MXene/CDs was synthesized to amplify oxidative stress under near-infrared laser irradiation. Well-exfoliated MXene nanosheets have proven to show an excellent photothermal effect for sterilization. The incorporation of CDs could provide photo-generated electrons for MXene nanosheets to generate ROS, meanwhile reducing the recombination of electron-hole pairs to further accelerate the generation of photo-generated electrons. The MXene/CDs material demonstrates outstanding synergistic photothermal and photodynamic effects, possesses excellent biocompatibility and successfully eliminates drug-resistant bacteria as well as inhibits biofilm formation. While attaining a remarkable killing efficiency of up to 99.99% against drug-resistant Escherichia coli and Staphylococcus aureus, it also demonstrates outstanding antibacterial effects against four additional bacterial strains. This work not only establishes a synthesis precedent for preparing high-entropy MXene materials with CDs but also provides a potential approach for addressing the issue of drug-resistant bacterial infections.

Nanobiostimulant action of trigolic formulated zinc sulfide nanoparticles (ZnS-T NPs) on rice seeds by triggering antioxidant defense network and plant growth specific transcription factors.

Under a changing climate, nanotechnological interventions for climate resilience in crops are critical to maintaining food security. Prior research has documented the affirmative response of nano zinc sulfide (nZnS) on physiological traits of fungal-infested rice seeds. Here, we propose an application of trigolic formulated zinc sulfide nanoparticles (ZnS-T NPs) on rice seeds as nanobiostimulant to improve physiological parameters by triggering antioxidative defense system, whose mechanism was investigated at transcriptional level by differential expression of genes in germinated seedlings. Nanopriming of healthy rice seeds with ZnS-T NPs (50 µg/ml), considerably intensified the seed vitality factors, including germination percentage, seedling length, dry weight and overall vigor index. Differential activation of antioxidant enzymes, viz. SOD (35.47%), APX (33.80%) and CAT (45.94%), in ZnS-T NPs treated seedlings reduced the probability of redox imbalance and promoted the vitality of rice seedlings. In gene expression profiling by reverse transcription quantitative real time PCR (qRT-PCR), the notable up-regulation of target antioxidant genes (CuZn SOD, APX and CAT) and plant growth specific genes (CKX and GRF) in ZnS-T NPs treated rice seedlings substantiates their molecular role in stimulating both antioxidant defenses and plant growth mechanisms. The improved physiological quality parameters of ZnS-T NPs treated rice seeds under pot house conditions corresponded well with in vitro findings, which validated the beneficial boosted impact of ZnS-T NPs on rice seed development. Inclusively, the study on ZnS-T NPs offers fresh perspectives into biochemical and molecular reactions of rice, potentially positioning them as nanobiostimulant capable of eliciting broad-spectrum immune and growth-enhancing responses.

Widespread S-persulfidation in activated macrophages as a protective mechanism against oxidative-inflammatory stress.

Acute inflammatory responses often involve the production of reactive oxygen and nitrogen species by innate immune cells, particularly macrophages. How activated macrophages protect themselves in the face of oxidative-inflammatory stress remains a long-standing question. Recent evidence implicates reactive sulfur species (RSS) in inflammatory responses; however, how endogenous RSS affect macrophage function and response to oxidative and inflammatory insults remains poorly understood. In this study, we investigated the endogenous pathways of RSS biogenesis and clearance in macrophages, with a particular focus on exploring how hydrogen sulfide (H2S)-mediated S-persulfidation influences macrophage responses to oxidative-inflammatory stress. We show that classical activation of mouse or human macrophages using lipopolysaccharide and interferon-γ (LPS/IFN-γ) triggers substantial production of H2S/RSS, leading to widespread protein persulfidation. Biochemical and proteomic analyses revealed that this surge in cellular S-persulfidation engaged ∼2% of total thiols and modified over 800 functionally diverse proteins. S-persulfidation was found to be largely dependent on the cystine importer xCT and the H2S-generating enzyme cystathionine γ-lyase and was independent of changes in the global proteome. We further investigated the role of the sulfide-oxidizing enzyme sulfide quinone oxidoreductase (SQOR), and found that it acts as a negative regulator of S-persulfidation. Elevated S-persulfidation following LPS/IFN-γ stimulation or SQOR inhibition was associated with increased resistance to oxidative stress. Upregulation of persulfides also inhibited the activation of the macrophage NLRP3 inflammasome and provided protection against inflammatory cell death. Collectively, our findings shed light on the metabolism and effects of RSS in macrophages and highlight the crucial role of persulfides in enabling macrophages to withstand and alleviate oxidative-inflammatory stress.

Garlic oil supplementation blocks inflammatory pyroptosis-related acute lung injury by suppressing the NF-κB/NLRP3 signaling pathway via H2S generation.

Acute lung injury (ALI) is a major cause of acute respiratory failure with a high morbidity and mortality rate, and effective therapeutic strategies for ALI remain limited. Inflammatory response is considered crucial for the pathogenesis of ALI. Garlic, a globally used cooking spice, reportedly exhibits excellent anti-inflammatory bioactivity. However, protective effects of garlic against ALI have never been reported. This study aimed to investigate the protective effects of garlic oil (GO) supplementation on lipopolysaccharide (LPS)-induced ALI models. Hematoxylin and eosin staining, pathology scores, lung myeloperoxidase (MPO) activity measurement, lung wet/dry (W/D) ratio detection, and bronchoalveolar lavage fluid (BALF) analysis were performed to investigate ALI histopathology. Real-time polymerase chain reaction, western blotting, and enzyme-linked immunosorbent assay were conducted to evaluate the expression levels of inflammatory factors, nuclear factor-κB (NF-κB), NLRP3, pyroptosis-related proteins, and H2S-producing enzymes. GO attenuated LPS-induced pulmonary pathological changes, lung W/D ratio, MPO activity, and inflammatory cytokines in the lungs and BALF. Additionally, GO suppressed LPS-induced NF-κB activation, NLRP3 inflammasome expression, and inflammatory-related pyroptosis. Mechanistically, GO promoted increased H2S production in lung tissues by enhancing the conversion of GO-rich polysulfide compounds or by increasing the expression of H2S-producing enzymes in vivo. Inhibition of endogenous or exogenous H2S production reversed the protective effects of GO on ALI and eliminated the inhibitory effects of GO on NF-κB, NLRP3, and pyroptotic signaling pathways. Overall, these findings indicate that GO has a critical anti-inflammatory effect and protects against LPS-induced ALI by suppressing the NF-κB/NLRP3 signaling pathway via H2S generation.

Diallyl Trisulfide Acts as a Soil Disinfestation Against the Ilyonectria destructans through Inducing the Burst of Reactive Oxygen Species.

Soil-borne diseases represent an impediment to the sustainable development of agriculture. A soil-borne disease caused by Ilyonectria destructans severely impacts Panax species, and soil disinfestation has proven to be an effective management approach. Here, diallyl trisulfide (DATS), derived from garlic, exhibited pronounced inhibitory effects on the growth of I. destructans in vitro tests and contributed to the alleviation of soil-borne diseases in the field. A comprehensive analysis demonstrated that DATS inhibits the growth of I. destructans by activating detoxifying enzymes, such as GSTs, disrupting the equilibrium of redox reactions. A series of antioxidant amino acids were suppressed by DATS. Particularly noteworthy is the substantial depletion of glutathione by DATS, resulting in the accumulation of ROS, ultimately culminating in the inhibition of I. destructans growth. Briefly, DATS could effectively suppress soil-borne diseases by inhibiting pathogen growth through the activation of ROS, and it holds promise as a potential environmentally friendly soil disinfestation.

Montelukast and cefoperazone act as antiquorum sensing and antibiofilm agents against Pseudomonas aeruginosa.

AIMS: Drug repurposing is an attractive strategy to control biofilm-related infectious diseases. In this study, two drugs (montelukast and cefoperazone) with well-established therapeutic applications were tested on Pseudomonas aeruginosa quorum sensing (QS) inhibition and biofilm control. METHODS AND RESULTS: The activity of montelukast and cefoperazone was evaluated for Pqs signal inhibition, pyocyanin synthesis, and prevention and eradication of Ps. aeruginosa biofilms. Cefoperazone inhibited the Pqs system by hindering the production of the autoinducer molecules 2-heptyl-4-hydroxyquinoline (HHQ) and 2-heptyl-3-hydroxy-4(1H)-quinolone (the Pseudomonas quinolone signal or PQS), corroborating in silico results. Pseudomonas aeruginosa pyocyanin production was reduced by 50%. The combination of the antibiotics cefoperazone and ciprofloxacin was synergistic for Ps. aeruginosa biofilm control. On the other hand, montelukast had no relevant effects on the inhibition of the Pqs system and against Ps. aeruginosa biofilm. CONCLUSION: This study provides for the first time strong evidence that cefoperazone interacts with the Pqs system, hindering the formation of the autoinducer molecules HHQ and PQS, reducing Ps. aeruginosa pathogenicity and virulence. Cefoperazone demonstrated a potential to be used in combination with less effective antibiotics (e.g. ciprofloxacin) to potentiate the biofilm control action.

In pursuit of feedback activation: New insights into redox-responsive hydropersulfide prodrug combating oxidative stress.

Redox-responsive hydropersulfide prodrugs are designed to enable a more controllable and efficient hydropersulfide (RSSH) supply and to thoroughly explore their biological and therapeutic applications in oxidative damage. To obtain novel activation patterns triggered by redox signaling, we focused on NAD(P)H: quinone acceptor oxidoreductase 1 (NQO1), a canonical antioxidant enzyme, and designed NQO1-activated RSSH prodrugs. We also performed a head-to-head comparison of two mainstream structural scaffolds with solid quantitative analysis of prodrugs, RSSH, and metabolic by-products by LC-MS/MS, confirming that the perthiocarbamate scaffold was more effective in intracellular prodrug uptake and RSSH production. The prodrug was highly potent in oxidative stress management against cisplatin-induced nephrotoxicity. Strikingly, this prodrug possessed potential feedback activation properties by which the delivered RSSH can further escalate the prodrug activation via NQO1 upregulation. Our strategy pushed RSSH prodrugs one step further in the pursuit of efficient release in biological matrices and improved druggability against oxidative stress.

Sulfide catabolism in hibernation and neuroprotection.

The mammalian brain is exquisitely vulnerable to lack of oxygen. However, the mechanism underlying the brain's sensitivity to hypoxia is incompletely understood. In this narrative review, we present a case for sulfide catabolism as a key defense mechanism of the brain against acute oxygen shortage. We will examine literature on the role of sulfide in hypoxia/ischemia, deep hibernation, and leigh syndrome patients, and present our recent data that support the neuroprotective effects of sulfide catabolism and persulfide production. When oxygen levels become low, hydrogen sulfide (H2S) accumulates in brain cells and impairs the ability of these cells to use the remaining, available oxygen to produce energy. In recent studies, we found that hibernating ground squirrels, which can withstand very low levels of oxygen, have high levels of sulfide:quinone oxidoreductase (SQOR) and the capacity to catabolize hydrogen sulfide in the brain. Silencing SQOR increased the sensitivity of the brain of squirrels and mice to hypoxia, whereas neuron-specific SQOR expression prevented hypoxia-induced sulfide accumulation, bioenergetic failure, and ischemic brain injury in mice. Excluding SQOR from mitochondria increased sensitivity to hypoxia not only in the brain but also in heart and liver. Pharmacological agents that scavenge sulfide and/or increase persulfide maintained mitochondrial respiration in hypoxic neurons and made mice resistant to ischemic injury to the brain or spinal cord. Drugs that oxidize hydrogen sulfide and/or increase persulfide may prove to be an effective approach to the treatment of patients experiencing brain injury caused by oxygen deprivation or mitochondrial dysfunction.

Research on different compound combinations of Realgar-Indigo naturalis formula to reverse acute promyelocytic leukemia arsenic resistance by regulating autophagy through mTOR pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: In China, the Chinese patent drug Realgar-Indigo naturalis Formula (RIF) is utilized for the therapy of acute promyelocytic leukemia (APL). Comprising four traditional Chinese herb-Realgar, Indigo naturalis, Salvia miltiorrhiza, and Pseudostellaria heterophylla-it notably includes tetra-arsenic tetra-sulfide, indirubin, tanshinone IIa, and total saponins of Radix Pseudostellariae as its primary active components. Due to its arsenic content, RIF distinctly contributes to the therapy for APL. However, the challenge of arsenic resistance in APL patients complicates the clinical use of arsenic agents. Interestingly, RIF demonstrates a high remission rate in APL patients, suggesting that its efficacy is not significantly compromised by arsenic resistance. Yet, the current state of research on RIF's ability to reverse arsenic resistance remains unclear. AIM OF THE STUDY: To investigate the mechanism of different combinations of the compound of RIF in reversing arsenic resistance in APL. MATERIALS AND METHODS: The present study utilized the arsenic-resistant HL60-PMLA216V-RARα cell line to investigate the effects of various RIF compounds, namely tetra-arsenic tetra-sulfide (A), indirubin (I), tanshinone IIa (T), and total saponins of Radix Pseudostellariae (S). The assessment of cell viability, observation of cell morphology, and evaluation of cell apoptosis were performed. Furthermore, the mitochondrial membrane potential, changes in the levels of PMLA216V-RARα, apoptosis-related factors, and the PI3K/AKT/mTOR pathway were examined, along with autophagy in all experimental groups. Meanwhile, we observed the changes about autophagy after blocking the PI3K or mTOR pathway. RESULTS: Tanshinone IIa, indirubin and total saponins of Radix Pseudostellariae could enhance the effect of tetra-arsenic tetra-sulfide down-regulating PMLA216V-RARα, and the mechanism was suggested to be related to inhibiting mTOR pathway to activate autophagy. CONCLUSIONS: We illustrated that the synergistic effect of different compound combinations of RIF can regulate autophagy through the mTOR pathway, enhance cell apoptosis, and degrade arsenic-resistant PMLA216V-RARα.

Hollow Copper Sulfide Photothermal Nanodelivery Platform Boosts Angiogenesis of Diabetic Wound by Scavenging Reactive Oxygen Species.

Sharply rising oxidative stress and ineffectual angiogenesis have imposed restrictions on diabetic wound healing. Here, a photothermal-responsive nanodelivery platform (HHC) was prepared by peroxidase (CAT)-loaded hollow copper sulfide dispersed in photocurable methacrylamide hyaluronan. The HHC could scavenge reactive oxygen species (ROS) and promote angiogenesis by photothermally driven CAT and Cu2+ release. Under near-infrared light irradiation, the HHC presented safe photothermal performance (<43 °C), efficient bacteriostatic ability against E. coli and S. aureus. It could rapidly release CAT into the external environment for decomposing H2O2 and oxygen generation to alleviate oxidative stress while promoting fibroblast migration and VEGF protein expression of endothelial cells by reducing intracellular ROS levels. The nanodelivery platform presented satisfactory therapeutic effects on murine diabetic wound healing by modulating tissue inflammation, promoting collagen deposition and increasing vascularization in the neodermis. This HHC provided a viable strategy for diabetic wound dressing design.

Hydrogen sulfide induces Ca2+ influx in the principal cells of rat cortical collecting ducts.

Hydrogen sulfide (H2S) acts as a gas-signaling agent in various tissues. Although it has been reported that endogenous enzymes that generate H2S are expressed abundantly in the kidney, few reports examine cellular responses to H2S in renal tubular epithelial cells. In this study, we investigated the effects of NaHS, an H2S donor, and l-cysteine, a substrate for H2S production, on the principal cells of rat cortical collecting ducts (CCDs). NaHS increased the intracellular Ca2+ concentration ([Ca2+]i) in the principal cells. The removal of extracellular Ca2+ largely attenuated the [Ca2+]i response. The TRPV4 channel blocker significantly inhibited the effect of NaHS. Extracellular administration of l-cysteine also elicited a rise in [Ca2+]i. Prior treatment of CCDs with AOAA, an inhibitor of H2S production enzyme, l-cysteine-induced [Ca2+]i response was significantly reduced. These results suggest that not only exogenous H2S but also endogenously produced H2S triggers the extracellular influx pathway of Ca2+ in the principal cells of rat CCDs.

The Garlic Compound, Diallyl Trisulfide, Attenuates Benzo[a]Pyrene-Induced Precancerous Effect through Its Antioxidant Effect, AhR Inhibition, and Increased DNA Repair in Human Breast Epithelial Cells.

Exposure to B[a]P, the most characterized polycyclic aromatic hydrocarbon, significantly increases breast cancer risk. Our lab has previously reported that diallyl trisulfide (DATS), a garlic organosulfur compound (OSC) with chemopreventive and cell cycle arrest properties, reduces lipid peroxides and DNA damage in normal breast epithelial (MCF-10A) cells. In this study, we evaluated the ability of DATS to block the B[a]P-induced initiation of carcinogenesis in MCF-10A cells by examining changes in proliferation, clonogenic formation, reactive oxygen species (ROS) formation, 8-hydroxy-2-deoxyguanosine (8-OHdG) levels, and protein expression of ARNT/HIF-1ß, CYP1A1, and DNA POLß. The study results indicate that B[a]P increased proliferation, clonogenic formation, ROS formation, and 8-OHdG levels, as well as increasing the protein expression of ARNT/HIF-1ß and CYP1A1 compared to the control. Conversely, DATS/B[a]P co-treatment (CoTx) inhibited cell proliferation, clonogenic formation, ROS formation, and 8-OHdG levels compared to B[a]P alone. Treatment with DATS significantly inhibited (p < 0.0001) AhR expression, implicated in the development and progression of breast cancer. The CoTx also attenuated all the above-mentioned B[a]P-induced changes in protein expression. At the same time, it increased DNA POLß protein expression, which indicates increased DNA repair, thus causing a chemopreventive effect. These results provide evidence for the chemopreventive effects of DATS in breast cancer prevention.

Thioglucose-derived tetrasulfide, a unique polysulfide model compound.

Polysulfides have received increased interest in redox biology due to their role as the precursors of H2S and persulfides. However, the compounds that are suitable for biological investigations are limited to cysteine- and glutathione-derived polysulfides. In this work, we report the preparation and evaluation of a novel polysulfide derived from thioglucose, which represents the first carbohydrate-based polysulfide. This compound, thioglucose tetrasulfide (TGS4), showed excellent stability and water solubility. H2S and persulfide production from TGS4, as well as its associated antioxidative property were also demonstrated. Additionally, TGS4 was demonstrated to significantly induce cellular sulfane sulfur level increase, in particular for the formation of hydropersulfides/trisulfides. These results suggest that TGS4 is a useful tool for polysulfide research.

Diallyl trisulfide (DATS) protects cardiac cells against advanced glycation end-product-induced apoptosis by enhancing FoxO3A-dependent upregulation of miRNA-210.

Diabetic cardiomyopathy is a common complication of diabetes, resulting in cardiac hypertrophy and heart failure associated with excessive reactive oxygen species and mitochondria-mediated apoptosis generation. Mitogen-activated protein kinase-c-Jun N-terminal kinase (MAPK-JNK), regulated by microRNA (miR)-210, affects mitochondrial function and is activated by advanced glycation end-products (AGE) in cardiac cells. Diallyl trisulfide (DATS), an antioxidant in garlic oil, inhibits stress-induced cardiac apoptosis. This study examined whether DATS enhances miR-210 expression to attenuate cardiac apoptosis. We investigated the DATS-mediated attenuation mechanism of AGE-enhanced cardiac apoptosis by modulating miR-210 and its upstream transcriptional regulator, FoxO3a. We found FoxO3a binding sites in the miR-210 promoter region. Our results indicated that DATS treatment inhibited AGE-induced JNK activation, phosphoprotein c-Jun nuclear transactivation, and cardiac apoptosis and reversed the AGE-induced reduction in cardiac miR-210 levels. The luciferase activity after DATS treatment was significantly lower than that of the control and was reversed following AGE treatment. We also showed that FoxO3a, upregulated by DATS treatment, may bind to the miR-210 promoter to enhance its expression and downregulates JNK expression to attenuate AGE-induced cardiac apoptosis. Oral administration of DATS enhanced FoxO3a expression in the heart and reduced diabetes-induced heart apoptosis. Our findings indicate that DATS mediates AGE-induced cardiac cell apoptosis attenuation by promoting FoxO3a nuclear transactivation to enhance miR-210 expression and regulate JNK activation. Our results suggest that DATS can be used as a cardioprotective agent, and miR-210 is a critical regulator in inhibiting diabetic cardiomyopathy.

Garlic-derived compounds: Epigenetic modulators and their antitumor effects.

Cancer is a highly heterogeneous disease that poses a serious threat to human health worldwide. Despite significant advances in the diagnosis and treatment of cancer, the prognosis and survival rate of cancer remain poor due to late diagnosis, drug resistance, and adverse reactions. Therefore, it is very necessary to study the development mechanism of cancer and formulate effective therapeutic interventions. As widely available bioactive substances, natural products have shown obvious anticancer potential, especially by targeting abnormal epigenetic changes. The main active part of garlic is organic sulfur compounds, of which diallyl trisulfide (DATS) content is the highest, accounting for more than 40% of the total composition. The garlic-derived compounds have been recognized as an antioxidant for cancer prevention and treatment. However, the molecular mechanism of the antitumor effect of garlic-derived compounds remains unclear. Recent studies have identified garlic-derived compound DATS that plays critical roles in enhancing CpG demethylation or promoting histone acetylation as an epigenetic inhibitor. Here, we review the therapeutic progress of garlic-derived compounds against cancer through epigenetic pathways.

Synthesis, acaricidal activity, and structure-activity relationships of novel phenyl trifluoroethyl thioether derivatives containing substituted benzyl groups.

BACKGROUND: To discover and develop novel acaricidal compounds, a series of 2-fluoro-4-methyl/chlorine-5-((2,2,2-trifluoroethyl)thio)aniline/phenol compounds containing N/O-benzyl moieties were synthesized based on lead compound LZ-1. RESULTS: The activity of these compounds against carmine spider mites (Tetranychus cinnabarinus) was determined using the leaf-spray method. Bioassays indicated that most of the designed target compounds possessed moderate to excellent acaricidal activity against adult T. cinnabarinus. The median lethal concentrations of 25b and 26b were 0.683 and 2.448 mg L-1 against adult mites, respectively; exceeding those of bifenazate (7.519 mg L-1 ) and lead compound LZ-1(3.658 mg L-1 ). Compound 25b exhibited 100% mortality in T. cinnabarinus larvae at 10 mg L-1 . CONCLUSION: Continuing the study of these compounds in field trials, we compared the efficacy of mite killing by compound 25b with the commercial pesticide spirodiclofen and showed that mite control achieved 95.9% and 83.0% lethality at 10 and 22 days post-treatment. In comparison, spirodiclofen showed 92.7% lethality at 10 days and 77.2% lethality at 22 days post-treatment at a concentration of 100 mg L-1 . Results showed that 25b produced more facile and long-lasting control against T. cinnabarinus than the commercial acaricide spirodiclofen. Density functional theory analysis and electrostatic potential calculations of various molecular substitutions suggested some useful models to achieve other highly active miticidal compounds. © 2023 Society of Chemical Industry.

pH/glutathione dual-responsive copper sulfide-coated organic mesoporous silica for synergistic chemo-photothermal therapy.

Nanodrug delivery systems (NDSs), such as mesoporous silica, have been widely studied because of their high specific surface area, high loading rate, and easy modification; however, they are not easily metabolized and excreted by the human body and may be potentially harmful. Hence, we aimed to examine the synergistic anti-tumor effects of ex vivo chemo-photothermal therapy to develop a rational and highly biocompatible treatment protocol for tumors. We constructed a biodegradable NDS using organic mesoporous silica with a tetrasulfide bond structure, copper sulfide core, and folic acid-modified surface (CuS@DMONs-FA-DOX-PEG) to target a tumor site, dissociate, and release the drug. The degradation ability, photothermal conversion ability, hemocompatibility, and in vitro and in vivo anti-tumor effects of the CuS@DMONs-FA-DOX-PEG nanoparticles were evaluated. Our findings revealed that the nanoparticles encapsulated in copper sulfide exhibited significant photothermal activity and optimal photothermal conversion rate. Further, the drug was accurately delivered and released into the target tumor cells, annihilating them. This study demonstrated the successful preparation, safety, and synergistic anti-tumor effects of chemo-photothermal therapeutic nanomaterials.