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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Exploring the potential of the halotolerant bacterial strain Bacillus subtilis LN8B as an ecofriendly sulfide collector for seawater flotation.

AIM: To assess the effectiveness of Bacillus subtilis strain LN8B as a biocollector for recovering pyrite (Py) and chalcopyrite (CPy) in both seawater (Sw) and deionized water (Dw), and to explore the underlying adhesion mechanism in these bioflotation experiments. MATERIALS AND METHODS: The bioflotation test utilized B. subtilis strain LN8B as the biocollector through microflotation experiments. Additionally, frother methyl isobutyl carbinol (MIBC) and conventional collector potassium amyl xanthate (PAX) were introduced in some experiments. The zeta potential (ZP) and Fourier-transform infrared spectroscopy (FTIR) was employed to explore the adhesion mechanism of Py and CPy interacting with the biocollector in Sw and Dw. The adaptability of the B. subtilis strain to different water types and salinities was assessed through growth curves measuring optical density. Finally, antibiotic susceptibility tests were conducted to evaluate potential risks of the biocollector. RESULTS: Superior outcomes were observed in Sw where Py and CPy recovery was ∼39.3% ± 7.7% and 41.1% ± 5.8%, respectively, without microorganisms' presence. However, B. subtilis LN8B potentiate Py and CPy recovery, reaching 72.8% ± 4.9% and 84.6% ± 1.5%, respectively. When MIBC was added, only the Py recovery was improved (89.4% ± 3.6%), depicting an adverse effect for CPy (81.8% ± 1.1%). ZP measurements indicated increased mineral surface hydrophobicity when Py and CPy interacted with the biocollector in both Sw and Dw. FTIR revealed the presence of protein-related amide peaks, highlighting the hydrophobic nature of the bacterium. The adaptability of this strain to diverse water types and salinities was assessed, demonstrating remarkable growth versatility. Antibiotic susceptibility tests indicated that B. subtilis LN8B was susceptible to 23 of the 25 antibiotics examined, suggesting it poses minimal environmental risks. CONCLUSIONS: The study substantiates the biotechnological promise of B. subtilis strain LN8B as an efficient sulfide collector for promoting cleaner mineral production. This effectiveness is attributed to its ability to induce mineral surface hydrophobicity, a result of the distinct characteristics of proteins within its cell wall.

Diallyl trisulfide and its active metabolite allyl methyl sulfone attenuate cisplatin-induced nephrotoxicity by inhibiting the ROS/MAPK/NF-κB pathway.

Cisplatin, a chemotherapy medication employed in the treatment of various solid tumors, is constrained in its clinical application due to nephrotoxicity. Diallyl trisulfide (DATS), a compound derived from garlic that possessed anticancer and antioxidant properties, can be combined with cisplatin without hindering its antitumor effects. The present investigation examined the defensive properties of DATS and its active metabolites against renal dysfunction caused by cisplatin. We created a mouse model to study renal injury caused by cisplatin and assessed kidney histology, immunochemistry, and serum cytokines. DATS treatment effectively reduced the pathological changes caused by cisplatin by decreasing the levels of renal function markers BUN, CRE, cystatin C, NGAL, inflammatory factors TNF-α, IL-6, and the protein expression of α-SMA, NF-κB, KIM-1. A pharmacokinetic evaluation of DATS found that allyl methyl sulfone (AMSO2) was the most abundant and persistent metabolite of DATS in vivo. Then, we examined the impact of AMSO2 on cell viability, apoptosis, ROS generation, and MAPK/NF-κB pathways in HK-2 cells treated with cisplatin. Cotreatment with AMSO2 effectively hindered the HK-2 cells alterations induced by cisplatin. Furthermore, AMSO2 mitigated oxidative stress through the modulation of MAPK and NF-κB pathways. Our findings indicated that DATS and its active derivative AMSO2 attenuated cisplatin-induced nephrotoxicity. DATS shows potential as a viable treatment for nephrotoxicity caused by cisplatin.

Fatty Amine-Mediated Synthesis of Hierarchical Copper Sulfide Nanoflowers for Efficient NIR-II Photothermal Conversion and Antibacterial Performance.

Non-noble metal photothermal materials have recently attracted increasing attention as unique alternatives to noble metal-based ones due to advantages like earth abundance, cost-effectiveness, and large-scale application capability. In this study, hierarchical copper sulfide (CuS) nanostructures with tunable flower-like morphologies and dimensional sizes are prepared via a fatty amine-mediated one-pot polyol synthesis. In particular, the addition of fatty amines induces a significant decrease in the overall particle size and lamellar thickness, and their morphologies and sizes could be tuned using different types of fatty amines. The dense stacking of nanosheets with limited sizes in the form of such a unique hierarchical architecture facilitates the interactions of the electromagnetic fields between adjacent nanoplates and enables the creation of abundant hot-spot regions, thus, benefiting the enhanced second near-infrared (NIR-II) light absorptions. The optimized CuS nanoflowers exhibit a photothermal conversion efficiency of 37.6%, realizing a temperature increase of nearly 50 °C within 10 min under 1064 nm laser irradiations at a power density of 1 W cm-2. They also exhibit broad-spectrum antibacterial activity, rendering them promising candidates for combating a spectrum of bacterial infections. The present study offers a feasible strategy to generate nanosheet-based hierarchical CuS nanostructures and validates their promising use in photothermal conversion, which could find important use in NIR-II photothermal therapy.

Hydrogen sulfide production in the medullary respiratory center modulates the neural circuit for respiratory pattern and rhythm generations.

Hydrogen sulfide (H2S), which is synthesized in the brain, modulates the neural network. Recently, the importance of H2S in respiratory central pattern generation has been recognized, yet the function of H2S in the medullary respiratory network remains poorly understood. Here, to evaluate the functional roles of H2S in the medullary respiratory network, the Bötzinger complex (BötC), the pre-Bötzinger complex (preBötC), and the rostral ventral respiratory group (rVRG), we observed the effects of inhibition of H2S synthesis at each region on the respiratory pattern by using an in situ arterially perfused preparation of decerebrated male rats. After microinjection of an H2S synthase inhibitor, cystathionine ß-synthase, into the BötC or preBötC, the amplitude of the inspiratory burst decreased and the respiratory frequency increased according to shorter expiration and inspiration, respectively. These alterations were abolished or attenuated in the presence of a blocker of excitatory synaptic transmission. On the other hand, after microinjection of the H2S synthase inhibitor into the rVRG, the amplitude of the inspiratory burst was attenuated, and the respiratory frequency decreased, which was the opposite effect to those obtained by blockade of inhibitory synaptic transmission at the rVRG. These results suggest that H2S synthesized in the BötC and preBötC functions to limit respiratory frequency by sustaining the respiratory phase and to maintain the power of inspiration. In contrast, H2S synthesized in the rVRG functions to promote respiratory frequency by modulating the interval of inspiration and to maintain the power of inspiration. The underlying mechanism might facilitate excitatory synaptic transmission and/or attenuate inhibitory synaptic transmission.

Dissolving sodium hydrosulfide in drinking water is not a good source of hydrogen sulfide for animal studies.

Hydrogen sulfide (H2S) has many physiological and pathological roles in the human body. Sodium hydrosulfide (NaHS) is widely used as a pharmacological tool for assessing H2S effects in biological experiments. Although H2S loss from NaHS solution is a matter of minutes, some animal studies use NaHS in solution as an H2S-donating compound in drinking water. This study addresses whether 30 µM NaHS in drinking water prepared in rat/mouse water bottles remains stable for at least 12-24 h, as presumed by some authors. NaHS solutions (30 µM) were prepared in drinking water and immediately transferred to rat/mice water bottles. Samples were obtained from the tip of water bottles and from inside of the bottles at 0, 1, 2, 3, 4, 5, 6, 12, and 24 h for sulfide measurement using the methylene blue method. Furthermore, NaHS (30 µM) was administered to male and female rats for two weeks, and serum sulfide concentrations were measured every other day in the first week and at the end of the second week. NaHS solution was unstable in the samples obtained from the tip of water bottles; it declined by 72% and 75% after 12 and 24 h, respectively. In the samples obtained from the inside of the water bottles, the decline in the NaHS was not significant until 2 h; however, it decreased by 47% and 72% after 12 and 24 h, respectively. NaHS administration did not affect serum sulfide levels in male and female rats. In conclusion, NaHS solution prepared in drinking water can not be used for H2S donation as the solution is unstable. This route of administration exposes animals to variable and lower-than-expected amounts of NaHS.

The Impact of Cadmium Selenide Zinc Sulfide Quantum Dots on the Proteomic Profile of Saccharomyces cerevisiae.

Quantum dots (QDs) have been highly sought after in the past few decades for their potential to be used in many biomedical applications. However, QDs' cytotoxicity is still a major concern that limits the incorporation of QDs into cutting-edge technologies. Thus, it is important to study and understand the mechanism by which QDs exert their toxicity. Although many studies have explored the cytotoxicity of quantum dots through the transcriptomic level and reactive species generation, the impact of quantum dots on the expression of cellular protein remains unclear. Using Saccharomyces cerevisiae as a model organism, we studied the effect of cadmium selenide zinc sulfide quantum dots (CdSe/ZnS QDs) on the proteomic profile of budding yeast cells. We found a total of 280 differentially expressed proteins after 6 h of CdSe/ZnS QDs treatment. Among these, 187 proteins were upregulated, and 93 proteins were downregulated. The majority of upregulated proteins were found to be associated with transcription/RNA processing, intracellular trafficking, and ribosome biogenesis. On the other hand, many of the downregulated proteins are associated with cellular metabolic pathways and mitochondrial components. Through this study, the cytotoxicity of CdSe/ZnS QDs on the proteomic level was revealed, providing a more well-rounded knowledge of QDs' toxicity.

Ruthenium(II) Polypyridyl-Based Photocages for an Anticancer Phytochemical Diallyl Sulfide: Comparative Dark and Photoreactivity Studies of Caged and Precursor Uncaged Complexes.

The spatiotemporal control over the drug's action offered by ruthenium(II) polypyridyl complexes by the selective activation of the prodrug inside the tumor has beaconed toward much-desired selectivity issues in cancer chemotherapy. The photocaging of anticancer bioactive ligands attached synergistically with cytotoxic Ru(II) polypyridyl cores and selective release thereof in cancer cells are a promising modality for more effective drug action. Diallyl sulfide (DAS) naturally found in garlic has anticancer, antioxidant, and anti-inflammatory activities. Herein, we designed two Ru(II) polypyridyl complexes to cage DAS having a thioether-based donor site. For in-depth photocaging studies, we compared the reactivity of the DAS-caged compounds with the uncaged Ru(II)-complexes with the general formula [Ru(ttp)(NN)(L)]+/2+. Here, in the first series, ttp = p-tolyl terpyridine, NN = phen (1,10-phenanthroline), and L = Cl- (1-Cl) and H2O (1-H2O), while for the second series, NN = dpq (pyrazino[2,3-f][1,10]phenanthroline), and L = Cl- (2-Cl) and H2O (2-H2O). The reaction of DAS with 1-H2O and 2-H2O yielded the caged complexes [Ru(ttp)(NN)(DAS)](PF6)2, i.e., 1-DAS and 2-DAS, respectively. The complexes were structurally characterized by X-ray crystallography, and the solution-state characterization was done by 1H NMR and ESI-MS studies. Photoinduced release of DAS from the Ru(II) core was monitored by 1H NMR and UV-vis spectroscopy. When irradiated with a 470 nm blue LED in DMSO, the photosubstitution quantum yields (Φ) of 0.035 and 0.057 were observed for 1-DAS and 2-DAS, respectively. Intriguing solution-state speciation and kinetic behaviors of the uncaged and caged Ru(II)-complexes emerged from 1H NMR studies in the dark, and they are depicted in this work. The caged 1-DAS and 2-DAS complexes remained mostly structurally intact for a reasonably long period in DMSO. The uncaged 1-Cl and 2-Cl complexes, although did not undergo substitution in only DMSO but in the 10% DMSO/H2O mixture, completely converted to the corresponding DMSO-adduct within 16 h. Toward gaining insights into the reactivity with the biological targets, we observed that 1-Cl upon hydrolysis formed an adduct with 5'-GMP, while a small amount of GSSG-adduct was observed when 1-Cl was reacted with GSH in H2O at 323 K. 1-Cl after hydrolysis reacted with l-methionine, although the rate was slightly slower compared with that with DMSO, suggesting varying reaction kinetics with different sulfur-based linkages. Although 1-H2O reacted with sulfoxide and thioether ligands at room temperature, the rate was much faster at higher temperatures obviously, and thiol-based systems needed higher thermal energy for conjugation. Overall, these studies provide insight for thoughtful design of new generation Ru(II) polypyridyl complexes for caging suitable bioactive organic molecules.

The anti-inflammatory effect of dimethyl trisulfide in experimental acute pancreatitis.

Various organosulfur compounds, such as dimethyl trisulfide (DMTS), display anti-inflammatory properties. We aimed to examine the effects of DMTS on acute pancreatitis (AP) and its mechanism of action in both in vivo and in vitro studies. AP was induced in FVB/n mice or Wistar rats by caerulein, ethanol-palmitoleic acid, or L-ornithine-HCl. DMTS treatments were administered subcutaneously. AP severity was assessed by pancreatic histological scoring, pancreatic water content, and myeloperoxidase activity measurements. The behaviour of animals was followed. Pancreatic heat shock protein 72 (HSP72) expression, sulfide, and protein persulfidation were measured. In vitro acinar viability, intracellular Ca2+ concentration, and reactive oxygen species production were determined. DMTS dose-dependently decreased the severity of AP. It declined the pancreatic infiltration of leukocytes and cellular damage in mice. DMTS upregulated the HSP72 expression during AP and elevated serum sulfide and low molecular weight persulfide levels. DMTS exhibited cytoprotection against hydrogen peroxide and AP-inducing agents. It has antioxidant properties and modulates physiological but not pathophysiological Ca2+ signalling. Generally, DMTS ameliorated AP severity and protected pancreatic acinar cells. Our findings indicate that DMTS is a sulfur donor with anti-inflammatory and antioxidant effects, and organosulfur compounds require further investigation into this potentially lethal disease.

Mercuric-sulphide based metallopharmaceutical formulation as an alternative therapeutic to combat viral and multidrug-resistant (MDR) bacterial infections.

According to the Global Antimicrobial Resistance and Use Surveillance System (GLASS) data, antibiotic resistance escalates more challenges in treatment against communicable diseases worldwide. Henceforth, the use of combinational antimicrobial therapy and metal-conjugated phytoconstituents composites are considered as alternatives. The present study explored the efficacy of mercuric-sulfide-based metallopharmaceutical, Sivanar Amirtham for anti-bacterial, anti-tuberculosis, anti-HIV therapeutics and toxicity profile by haemolytic assay, first of its kind. The anti-bacterial study was performed against both gram-positive and gram-negative pathogens including Staphylococcus aureus (ATCC 29213), Methicillin-resistant Staphylococcus aureus (MRSA: ATCC 43300), Enterococcus faecalis (ATCC 29212), Pseudomonas aeruginosa (PA14) and Vibrio cholerae (MTCC 3905) by agar well diffusion assay, wherein the highest zone of inhibition was identified for MRSA (20.7 mm) and V. cholerae (34.3 mm) at 25 mg/mL. Furthermore, the anti-tuberculosis activity experimented by microtitre alamar blue assay against M. tuberculosis (ATCC 27294) demonstrated significant activity at the concentration range of 12.5-100 µg/mL. Additionally, the anti-HIV efficacy established by the syncytia inhibition method using C8166 cell lines infected with HIV-1IIIB, showed a significant therapeutic effect. The in-vitro toxicity assay proved Sivanar Amirtham to be non-haemolytic and haemocompatible. The physicochemical characterization studies revealed the nano-sized particles with different functional groups and the distinctive metal-mineral complex could be attributed to the multi-site targeting ability. The rationale evidence and scientific validation for the efficacy of Sivanar Amirtham ensures that it could be proposed as an alternative or adjuvant for both prophylactics and therapeutics to overcome HIV infection and antimicrobial resistance as well as the multi-drug resistance challenges.