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Background: Hydrogen gas and microalgae both exist in the natural environment. We aimed to integrate hydrogen gas and biology nano microalgae together to expand the treatment options in sepsis. Methods: Phosphoproteomics, metabolomics and proteomics data were obtained from mice undergoing cecum ligation and puncture (CLP) and inhalation of hydrogen gas. All omics analysis procedure were accordance with standards. Multi R packages were used in single cell and spatial transcriptomics analysis to identify primary cells expressing targeted genes, and the genes’ co-expression relationships in sepsis related lung landscape. Then, network pharmacology method was used to identify candidate drugs. We used hydrophobic-force-driving self-assembly method to construct dihydroquercetin (DQ) nanoparticle. To cooperate with molecular hydrogen, ammonia borane (B) was added to DQ surface. Then, Chlorella vulgaris (C) was used as biological carrier to improve self-assembly nanoparticle. Vivo and vitro experiments were both conducted to evaluate anti-inflammation, anti-ferroptosis, anti-infection and organ protection capability. Results: As a result, we identified Esam and Zo-1 were target phosphorylation proteins for molecular hydrogen treatment in lung. Ferroptosis and glutathione metabolism were two target pathways. Chlorella vulgaris improved the dispersion of DQB and reconstructed morphological features of DQB, formed DQB@C nano-system (size = 307.3 nm, zeta potential = −22mv), with well infection-responsive hydrogen release capability and biosafety. In addition, DQB@C was able to decrease oxidative stress and inflammation factors accumulation in lung cells. Through increasing expression level of Slc7a11/xCT and decreasing Cox2 level to participate with the regulation of ferroptosis. Also, DQB@C played lung and multi organ protection and anti-inflammation roles on CLP mice. Conclusion: Our research proposed DQB@C as a novel biology nano-system with enormous potential on treatment for sepsis related acute lung injury to solve the limitation of hydrogen gas utilization in clinics.

Mesenchymal stromal cells (MSCs) and MSC-derived extracellular vesicles (EVs) have emerged as innovative therapeutic agents for the treatment of sepsis and acute respiratory distress syndrome (ARDS). Although their potential remains undisputed in pre-clinical models, this has yet to be translated to the clinic. In this review, we focused on the role of microRNAs contained in MSC-derived EVs, the EV microRNAome, and their potential contribution to therapeutic mechanisms of action. The evidence that miRNA transfer in MSC-derived EVs has a role in the overall therapeutic effects is compelling. However, several questions remain regarding how to reconcile the stochiometric issue of the low copy numbers of the miRNAs present in the EV particles, how different miRNAs delivered simultaneously interact with their targets within recipient cells, and the best miRNA or combination of miRNAs to use as therapy, potency markers, and biomarkers of efficacy in the clinic. Here, we offer a molecular genetics and systems biology perspective on the function of EV microRNAs, their contribution to mechanisms of action, and their therapeutic potential. [ABSTRACT FROM AUTHOR]

Simple Summary: Triple-negative breast cancer (TNBC) is an aggressive, hard-to-treat form of breast cancer, accounting for about 15 percent of breast cancers. The aim of our study was to assess the potential added value of combining monophosphoester 2-aminoethyl dihydrogen phosphate (2-AEH2P), a molecule involved in phospholipid turnover with antiproliferative and pro-apoptotic properties toward cancer cells, and the antitumor BR2 cell-penetrating peptide for TNBC treatment. Using an array of TNBC cells, our data demonstrate that, while possessing limited anti-cancer properties when used as single agents, a drastic synergy was observed with the association 2-AEH2P+BR2. Mechanistically, the 2-AEH2P+BR2 combination acts by inducing TNBC cells, but not normal cells, apoptosis and by preventing their migration potential through the modulation of cell death-related proteins, reduction of the mitochondrial potential and intracellular redistribution of important components such as the cytoskeleton. Our observations provide a clear rationale for the association of 2-AEH2P with the BR2 peptide as a new TNBC treatment. Breast cancer is the most common cancer in women, the so-called "Triple-Negative Breast Cancer" (TNBC) subtype remaining the most challenging to treat, with low tumor-free survival and poor clinical evolution. Therefore, there is a clear medical need for innovative and more efficient treatment options for TNBC. The aim of the present study was to evaluate the potential therapeutic interest of the association of the tumor-penetrating BR2 peptide with monophosphoester 2-aminoethyl dihydrogen phosphate (2-AEH2P), a monophosphoester involved in cell membrane turnover, in TNBC. For that purpose, viability, migration, proliferative capacity, and gene expression analysis of proteins involved in the control of proliferation and apoptosis were evaluated upon treatment of an array of TNBC cells with the BR2 peptide and 2-AEH2P, either separately or combined. Our data showed that, while possessing limited single-agent activity, the 2-AEH2P+BR2 association promoted significant cytotoxicity in TNBC cells but not in normal cells, with reduced proliferative potential and inhibition of cell migration. Mechanically, the 2-AEH2P+BR2 combination promoted an increase in cells expressing p53 caspase 3 and caspase 8, a reduction in cells expressing tumor progression and metastasis markers such as VEGF and PCNA, as well as a reduction in mitochondrial electrical potential. Our results indicate that the combination of the BR2 peptide with 2-AEH2P+BR2 may represent a promising therapeutic strategy in TNBC with potential use in clinical settings. [ABSTRACT FROM AUTHOR]

Background: Hydrogen gas and microalgae both exist in the natural environment. We aimed to integrate hydrogen gas and biology nano microalgae together to expand the treatment options in sepsis., Methods: Phosphoproteomics, metabolomics and proteomics data were obtained from mice undergoing cecum ligation and puncture (CLP) and inhalation of hydrogen gas. All omics analysis procedure were accordance with standards. Multi R packages were used in single cell and spatial transcriptomics analysis to identify primary cells expressing targeted genes, and the genes' co-expression relationships in sepsis related lung landscape. Then, network pharmacology method was used to identify candidate drugs. We used hydrophobic-force-driving self-assembly method to construct dihydroquercetin (DQ) nanoparticle. To cooperate with molecular hydrogen, ammonia borane (B) was added to DQ surface. Then, Chlorella vulgaris (C) was used as biological carrier to improve self-assembly nanoparticle. Vivo and vitro experiments were both conducted to evaluate anti-inflammation, anti-ferroptosis, anti-infection and organ protection capability., Results: As a result, we identified Esam and Zo-1 were target phosphorylation proteins for molecular hydrogen treatment in lung. Ferroptosis and glutathione metabolism were two target pathways. Chlorella vulgaris improved the dispersion of DQB and reconstructed morphological features of DQB, formed DQB@C nano-system (size = 307.3 nm, zeta potential = -22mv), with well infection-responsive hydrogen release capability and biosafety. In addition, DQB@C was able to decrease oxidative stress and inflammation factors accumulation in lung cells. Through increasing expression level of Slc7a11/xCT and decreasing Cox2 level to participate with the regulation of ferroptosis. Also, DQB@C played lung and multi organ protection and anti-inflammation roles on CLP mice., Conclusion: Our research proposed DQB@C as a novel biology nano-system with enormous potential on treatment for sepsis related acute lung injury to solve the limitation of hydrogen gas utilization in clinics., Competing Interests: No conflict of interest exits in the submission of this manuscript, and manuscript is approved by all authors for publication. I would like to declare on behalf of my co-authors that the work described was original research that has not been published previously. All the authors listed have approved the manuscript that is enclosed., (© 2024 The Authors.)

Effects of the Adenosine A1 blockade using 8-cyclopentyl-1,3-diprophyxanthine (DPCPX) nanoconjugate on inducing recovery of the hemidiaphragm paralyzed by hemisection have been thoroughly examined previously; however, the toxicology of DPCPX nanoconjugate remains unknown. This research study investigates the therapeutic efficacy and toxicology of the nanoconjugate DPCPX in the cervical spinal cord injury (SCI) rat model. We hypothesized that a single injection of nanoconjugate DPCPX in the paralyzed left hemidiaphragm (LDH) of hemisected rats at the 2nd cervical segment (C2Hx) would lead to the long-term recovery of LDH while showing minimal toxicity. Adult male rats underwent left C2Hx surgery and the diaphragms' baseline electromyography (EMG). Subsequently, rats were randomized into a control group and four treated subgroups. Three subgroups received a single intradiaphragmatic dose of either 0.09, 0.15, or 0.27 μg/kg, and one subgroup received 0.1 μg/kg of native DPCPX two times per day intravenously (i.v.) for 3 days (total 0.6 μg/kg). Rats were monitored for a total of 56 days. Compared with control, the treatment with nanoconjugate DPCPX at 0.09 μg/kg, 0.15 μg/kg, and 0.27 μg/kg doses elicited significant recovery of paralyzed LDH (i.e., 67% recovery at 8 wk) (P < 0.05). DPCPX nanoconjugate-treated rats had significant weight loss for first 2 wk but recovered significantly by day 56 (P < 0.05). The levels of gold in the blood and body tissues were below the recommended levels. No sign of weakness, histology of tissue damage, or organ abnormality was observed. A dose of DPCPX nanoconjugate can induce long-term diaphragm recovery after SCI without observed toxicity. [ABSTRACT FROM AUTHOR]

Although multifarious tumor-targeting modifications of nanoparticulate systems have been attempted in joint efforts by our predecessors, it remains challenging for nanomedicine to traverse physiological barriers involving blood vessels, tissues, and cell barriers to thereafter demonstrate excellent antitumor effects. To further overcome these inherent obstacles, we designed and prepared mycoplasma membrane (MM)-fused liposomes (LPs) with the goal of employing circulating neutrophils with the advantage of inflammatory cytokine-guided autonomous tumor localization to transport nanoparticles. We also utilized in vivo neutrophil activation induced by the liposomal form of the immune activator resiquimod (LPs-R848). Fused LPs preparations retained mycoplasma pathogen characteristics and achieved rapid recognition and endocytosis by activated neutrophils stimulated by LPs-R848. The enhanced neutrophil infiltration in homing of the inflammatory tumor microenvironment allowed more nanoparticles to be delivered into solid tumors. Facilitated by the formation of neutrophil extracellular traps (NETs), podophyllotoxin (POD)-loaded MM-fused LPs (MM-LPs-POD) were concomitantly released from neutrophils and subsequently engulfed by tumor cells during inflammation. MM-LPs-POD displayed superior suppression efficacy of tumor growth and lung metastasis in a 4T1 breast tumor model. Overall, such a strategy of pathogen-mimicking nanoparticles hijacking neutrophils in situ combined with enhanced neutrophil infiltration indeed elevates the potential of chemotherapeutics for tumor targeting therapy. A mycoplasma membrane-modified nano-drug delivery system in combination with immune activator resiquimod (R848) was developed to promote tumor-targeted accumulation of chemotherapeutics, providing a promising neutrophil-based platform for synergistic oncology therapy. [Display omitted] [ABSTRACT FROM AUTHOR]

Lung cancer is the most dangerous, malignant melanoma is the most aggressive, and cervical cancer has become more common in youngsters. PDT causes light-dependent and ROS-related cell death with non-toxic photosensitizers (PS). PDT can treat many malignancies, but cancer stem cells (CSCs), a subset of tumor cells that can initiate and relapse, may resist treatment. This study examined the effects of AlPcS4Cl - nanoPDT using gold nanoparticles (AuNPs) on lung, cervical, and melanoma CSCs. Intracellular localization of the drug compound and biochemical assays including viability, proliferation, cytotoxicity, and Annexin VPI cell death were performed together with morphological examination. The results demonstrate increased absorption and localization of the therapeutic molecule in CSCs. A decrease in CSC survival and proliferation, enhanced cytotoxicity, and apoptotic cell death confirmed the drug's efficacy. The results demonstrated that when AuNPs were utilized as a drug carrier for AlPcS 4 Cl, the PDT's effects were amplified, culminating in the complete annihilation of CSCs. [ABSTRACT FROM AUTHOR]

Recent developments in nanotechnology have brought new approaches to cancer diagnosis and therapy. While enhanced permeability and retention effect promotes nano-chemotherapeutics extravasation, the abnormal tumor vasculature, high interstitial pressure and dense stroma structure limit homogeneous intratumoral distribution of nano-chemotherapeutics and compromise their imaging and therapeutic effect. Moreover, heterogeneous distribution of nano-chemotherapeutics in non-tumor-stroma cells damages the non-tumor cells, and interferes with tumor-stroma crosstalk. This can lead not only to inhibition of tumor progression, but can also paradoxically induce acquired resistance and facilitate tumor cell proliferation and metastasis. Overall, the tumor microenvironment plays a vital role in regulating nano-chemotherapeutics distribution and their biological effects. In this review, the barriers in tumor microenvironment, its consequential effects on nano-chemotherapeutics, considerations to improve nano-chemotherapeutics delivery and combinatory strategies to overcome acquired resistance induced by tumor microenvironment have been summarized. The various strategies viz., nanotechnology based approach as well as ligand-mediated, redox-responsive, and enzyme-mediated based combinatorial nanoapproaches have been discussed in this review.

The changes in lifestyle and living conditions have affected not only humans but also microorganisms. As man invents new drugs and therapies, pathogens alter themselves to survive and thrive. Multiple drug resistance (MDR) is the talk of the town for decades now. Many generations of medications have been termed useless as MDR rises among the infectious population. The surge in nanotechnology has brought a new hope in reducing this aspect of resistance in pathogens. It has been observed in several laboratory-based studies that the use of nanoparticles had a synergistic effect on the antibiotic being administered to the pathogen; several resistant strains scummed to the stress created by the nanoparticles and became susceptible to the drug. The major cause of resistance to date is the efflux system, which makes the latest generation of antibiotics ineffective without reaching the target site. If species-specific nanomaterials are used to control the activity of efflux pumps, it could revolutionize the field of medicine and make the previous generation resistant medications active once again. Therefore, the current study was devised to assess and review nanoparticles' role on efflux systems and discuss how specialized particles can be designed towards an infectious host's particular drug ejection systems. • Nanotechnology plays an important role in drug development against multi-drug resistant organisms (MDROs). • Efflux mechanism of bacterial strains hinder the effect of antibiotics. • Nanoparticles are smaller in size easily bind on the cell membrane/efflux pumps to make bacteria sensitive to drugs. • Predominantly used nanoparticles are silver, gold, zinc, chitosan, nitric oxide, magnesium, copper, iron, calcium, platinum. • Efflux system of both gram positive and gram negative bacteria was inhibited by nanoparticles. [ABSTRACT FROM AUTHOR]

Effects of the Adenosine A1 blockade using 8-cyclopentyl-1,3-diprophyxanthine (DPCPX) nanoconjugate on inducing recovery of the hemidiaphragm paralyzed by hemisection have been thoroughly examined previously; however, the toxicology of DPCPX nanoconjugate remains unknown. This research study investigates the therapeutic efficacy and toxicology of the nanoconjugate DPCPX in the cervical spinal cord injury (SCI) rat model. We hypothesized that a single injection of nanoconjugate DPCPX in the paralyzed left hemidiaphragm (LDH) of hemisected rats at the 2nd cervical segment (C2Hx) would lead to the long-term recovery of LDH while showing minimal toxicity. Adult male rats underwent left C2Hx surgery and the diaphragms' baseline electromyography (EMG). Subsequently, rats were randomized into a control group and four treated subgroups. Three subgroups received a single intradiaphragmatic dose of either 0.09, 0.15, or 0.27 µg/kg, and one subgroup received 0.1 mg/kg of native DPCPX two times per day intravenously (i.v.) for 3 days (total 0.6 mg/kg). Rats were monitored for a total of 56 days. Compared with control, the treatment with nanoconjugate DPCPX at 0.09 µg/kg, 0.15 µg/kg, and 0.27 µg/kg doses elicited significant recovery of paralyzed LDH (i.e., 67% recovery at 8 wk) ( P < 0.05). DPCPX nanoconjugate-treated rats had significant weight loss for first 2 wk but recovered significantly by day 56 ( P < 0.05). The levels of gold in the blood and body tissues were below the recommended levels. No sign of weakness, histology of tissue damage, or organ abnormality was observed. A dose of DPCPX nanoconjugate can induce long-term diaphragm recovery after SCI without observed toxicity. NEW & NOTEWORTHY The intradiaphragmatic administration of nanoconjugate is safe and has the promise to significantly reduce the therapeutic dosage for the treatment and achieve long-term and possibly permanent recovery in respiratory muscle dysfunction after SCI. No toxicity of nanoconjugate was found in any of the experimental animals.