Vishaghn Dhoop, Nano-Scale Particles with Detoxifying Medicinal Fume, Exhibits Robust Anti-Microbial Activities: Implications of Disinfection Potentials of a Traditional Ayurvedic Air Sterilization Technique

The rapidly increasing global burden of healthcare associated infections (HAI) is resulting in proportionate increase in chemical disinfection in healthcare settings, adding an extra burden of environmental toxicity. Therefore, alternative disinfection techniques with less or no adverse side-effects need to be explored. In this regard, ayurvedic ‘ dhoopan’ technique involving slow combustion of medicinal herbs, minerals and animal products hold great promise. In this study, dhoopan of a traditionally defined ayurvedic medicinal mix, ‘Vishaghn Dhoop’ (VD) has been assessed for its anti-microbial potentials against both Gram-positive and negative pathogenic bacteria, Mycobacterium and pathogenic fungus, Candida albicans. Fume generated from slow combustion of VD was subjected to physico-chemical characterization and was assessed for anti-microbial effects. VD fume contained particles of 354 ± 84 nm size, laden with anti-microbial metabolites. On agar plates, VD fumigation reduced bacterial growth by 13 - 38%. Liquid culture aeration with VD fume inhibited bacterial growth by 50 - 85%, and fungal growth by 80%. In real life settings (in vivo), un-sanitized rooms fumigated with VD fumes for 30 min reduced the environmental microbial loads by 10 folds. In addition, the safety of VD fumigation was evaluated through in vitro cytotoxicity assay on human lung epithelial (A549) cells. Cells exposed to media-collected VD fumes for 24 h exhibited normal cyto-safety profile. Collectively, these observations provide scientific evidence in support of a traditional technique of disinfection, which can be fine-tuned to have implications in clinical, healthcare and food industry where, disinfection is a prime requirement.

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Assessment of SnFe2O4 Nanoparticles for Potential Application in Theranostics: Synthesis, Characterization, In Vitro, and In Vivo Toxicity

Materials ◽

10.3390/ma14040825 ◽

2021 ◽

Vol 14 (4) ◽

pp. 825

Author(s):

Saman Sargazi ◽

Mohammad Reza Hajinezhad ◽

Abbas Rahdar ◽

Muhammad Nadeem Zafar ◽

Aneesa Awan ◽

...

Keyword(s):

Electron Microscopy ◽

A549 Cells ◽

In Vitro Cytotoxicity ◽

Hek293 Cells ◽

Hydrothermal Route ◽

X Ray ◽

Tin Chloride ◽

Bet Analysis

In this research, tin ferrite (SnFe2O4) NPs were synthesized via hydrothermal route using ferric chloride and tin chloride as precursors and were then characterized in terms of morphology and structure using Fourier-transform infrared spectroscopy (FTIR), Ultraviolet–visible spectroscopy (UV-Vis), X-ray power diffraction (XRD), Scanning electron microscopy (SEM), Transmission electron microscopy (TEM), and Brunauer–Emmett–Teller (BET) method. The obtained UV-Vis spectra was used to measure band gap energy of as-prepared SnFe2O4 NPs. XRD confirmed the spinel structure of NPs, while SEM and TEM analyses disclosed the size of NPs in the range of 15–50 nm and revealed the spherical shape of NPs. Moreover, energy dispersive X-ray spectroscopy (EDS) and BET analysis was carried out to estimate elemental composition and specific surface area, respectively. In vitro cytotoxicity of the synthesized NPs were studied on normal (HUVEC, HEK293) and cancerous (A549) human cell lines. HUVEC cells were resistant to SnFe2O4 NPs; while a significant decrease in the viability of HEK293 cells was observed when treated with higher concentrations of SnFe2O4 NPs. Furthermore, SnFe2O4 NPs induced dramatic cytotoxicity against A549 cells. For in vivo study, rats received SnFe2O4 NPs at dosages of 0, 0.1, 1, and 10 mg/kg. The 10 mg/kg dose increased serum blood urea nitrogen and creatinine compared to the controls (P < 0.05). The pathology showed necrosis in the liver, heart, and lungs, and the greatest damages were related to the kidneys. Overall, the in vivo and in vitro experiments showed that SnFe2O4 NPs at high doses had toxic effects on lung, liver and kidney cells without inducing toxicity to HUVECs. Further studies are warranted to fully elucidate the side effects of SnFe2O4 NPs for their application in theranostics.

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Synthesis and high antiproliferative activity of dehydroabietylamine pyridine derivatives in vitro and in vivo

Biochemical Journal ◽

10.1042/bcj20200337 ◽

2020 ◽

Vol 477 (12) ◽

pp. 2383-2399

Author(s):

Fengyi Zhao ◽

Wen Lu ◽

Yuanyuan Xu ◽

Li Xu ◽

Jingjing Zhang ◽

...

Keyword(s):

Umbilical Vein ◽

A549 Cells ◽

Great Promise ◽

Pyridine Derivatives ◽

Inhibition Rate ◽

Low Toxicity ◽

A549 Lung ◽

Mcf 7

Several bioactive dehydroabietylamine Schiff-bases (L1−L4), amides (L5−L11) and complex CuL3(NO3)2, Cu(L5)3, Co(L6)2Cl2 had been synthesized successfully for developing more efficient but lower toxic antiproliferative compounds. Their antiproliferative activities to Hela (cervix), HepG2 (liver), MCF-7 (breast), A549 (lung) and HUVEC (umbilical vein, normal cell) were investigated in vitro. The toxicity of all compounds was less than dehydroabietylamine (L0). For HepG2 cells, L1, L2 and L3 had higher anti-HepG2 activity, especially L1 (0.52 µM) had highest anti-HepG2 activity but low toxicity. For MCF-7 cells, L1, L2, L3 and L4 had higher anti-MCF-7 activity, especially L3(0.49 µM) had highest anti-MCF-7 activity but low toxicity. For A549 cells, L2 and L3 had higher anti-A549 activity. Furthermore, L1 and L3 may be the great promise antiproliferative drugs with nontoxic side effects, due to the high anti-HepG2 and anti-MCF-7 inhibition rate in vivo, 65% and 61%, respectively. L1, L2 and L3 could induce apoptosis through intercalating into DNA.

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Bacterial variability in the mammalian gut captured by a single-cell synthetic oscillator

Nature Communications ◽

10.1038/s41467-019-12638-z ◽

2019 ◽

Vol 10 (1) ◽

Cited By ~ 15

Author(s):

David T. Riglar ◽

David L. Richmond ◽

Laurent Potvin-Trottier ◽

Andrew A. Verdegaal ◽

Alexander D. Naydich ◽

...

Keyword(s):

Single Cell ◽

Bacterial Growth ◽

Real Life ◽

Cell Level ◽

Bacterial Dynamics ◽

Genetic Oscillator ◽

Periodic Gene ◽

Periodic Gene Expression

Abstract Synthetic gene oscillators have the potential to control timed functions and periodic gene expression in engineered cells. Such oscillators have been refined in bacteria in vitro, however, these systems have lacked the robustness and precision necessary for applications in complex in vivo environments, such as the mammalian gut. Here, we demonstrate the implementation of a synthetic oscillator capable of keeping robust time in the mouse gut over periods of days. The oscillations provide a marker of bacterial growth at a single-cell level enabling quantification of bacterial dynamics in response to inflammation and underlying variations in the gut microbiota. Our work directly detects increased bacterial growth heterogeneity during disease and differences between spatial niches in the gut, demonstrating the deployment of a precise engineered genetic oscillator in real-life settings.

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Irradiation-Enhanced Cytotoxicity of Zinc Oxide Nanoparticles

International Journal of Toxicology ◽

10.1177/1091581814529168 ◽

2014 ◽

Vol 33 (3) ◽

pp. 187-203 ◽

Cited By ~ 18

Author(s):

Qingbo Yang ◽

Yinfa Ma

Keyword(s):

Zinc Oxide ◽

Visible Light ◽

Critical Role ◽

A549 Cells ◽

In Vitro Cytotoxicity ◽

The Body ◽

Zno Nps ◽

Nuclear Regions

Zinc oxide (ZnO) nanoparticles (NPs) are being widely utilized in industry due to their versatile properties. The in vitro cytotoxicity findings and the potential for exposures to ZnO NP from different sources via different routes of entry into the body have raised public health concerns. Although recent studies have shown the cytotoxic effects of these NPs, including oxidative stress, apoptosis and necrosis induction, genotoxicity, and others, irradiation-induced cytotoxicity has not been systematically studied. The goal of this study was to determine whether irradiation in the forms of visible light (approximately 400-600 nm), ultraviolet (UV) A (366 nm), and UVC (254 nm) would affect ZnO NPs-induced cytotoxicity. The results of this study demonstrated that the cytotoxicity of 60 to 80 nm ZnO NPs to A549 cells is dosage, time, and wavelength dependent. Nuclear decomposition by ZnO NPs, prior to membrane deformation, was found to be enhanced when exposed to irradiation. This study suggests that this phenomenon may be attributed to the irradiation-induced formation of positively charged sites on the ZnO NPs, which enhances nuclear affinity and generation of reactive oxygen species. Finally, the data demonstrated that while ZnO NPs act preferentially toward nuclear regions, destructions of cell membrane and the cytosol have also been observed. The photocatalytic properties of ZnO NPs play a critical role during the early stages of cell death, and their effects were reduced through the use of an antioxidant, N-acetylcysteine. In conclusion, both visible light and UV irradiations have been found to enhance the cytotoxic effect of ZnO NPs on the A549 cell line. This finding supports the need for further in vivo exposure studies relevant to actual conditions to confirm whether combined irradiation and ZnO NP exposure could enhance the nanotoxicity of ZnO NPs.

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In vitro Cytotoxicity and Genotoxicity Analysis of Ten Tannery Chemicals Using SOS/umu Tests and High-content In vitro Micronucleus Tests

Combinatorial Chemistry & High Throughput Screening ◽

10.2174/1386207321666180330120248 ◽

2018 ◽

Vol 21 (4) ◽

pp. 262-270 ◽

Cited By ~ 1

Author(s):

Zehao Huang ◽

Na Li ◽

Kaifeng Rao ◽

Cuiting Liu ◽

Zijian Wang ◽

...

Keyword(s):

Micronucleus Test ◽

A549 Cells ◽

Quantitative Structure Activity Relationship ◽

In Vitro Cytotoxicity ◽

Cytotoxic Effects ◽

Qsar Analysis ◽

Cell Assays ◽

Micronucleus Tests ◽

Damaging Effects

Background: More than 2,000 chemicals have been used in the tannery industry. Although some tannery chemicals have been reported to have harmful effects on both human health and the environment, only a few have been subjected to genotoxicity and cytotoxicity evaluations. Objective: This study focused on cytotoxicity and genotoxicity of ten tannery chemicals widely used in China. Materials and Methods: DNA-damaging effects were measured using the SOS/umu test with Salmonella typhimurium TA1535/pSK1002. Chromosome-damaging and cytotoxic effects were determined with the high-content in vitro Micronucleus test (MN test) using the human-derived cell lines MGC-803 and A549. Conclusion: The cytotoxicity of the ten tannery chemicals differed somewhat between the two cell assays, with A549 cells being more sensitive than MGC-803 cells. None of the chemicals induced DNA damage before metabolism, but one was found to have DNA-damaging effects on metabolism. Four of the chemicals, DY64, SB1, DB71 and RR120, were found to have chromosome-damaging effects. A Quantitative Structure-Activity Relationship (QSAR) analysis indicated that one structural feature favouring chemical genotoxicity, Hacceptor-path3-Hacceptor, may contribute to the chromosome-damaging effects of the four MN-test-positive chemicals.

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Mixed Micelles as Nano Polymer Therapeutics of Docetaxel: Increased In vitro Cytotoxicity and Decreased In vivo Toxicity

Current Drug Delivery ◽

10.2174/1567201814666170621113637 ◽

2018 ◽

Vol 15 (4) ◽

pp. 564-575 ◽

Cited By ~ 5

Author(s):

Arehalli S. Manjappa ◽

Popat S. Kumbhar ◽

Prajakta S. Khopade ◽

Ajit B. Patil ◽

John I. Disouza

Keyword(s):

Mixed Micelles ◽

In Vitro Cytotoxicity ◽

Polymer Therapeutics ◽

In Vivo Toxicity

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Mannose Conjugated Starch Nanoparticles for Preferential Targeting of Liver Cancer

Current Drug Delivery ◽

10.2174/1567201817666200903171124 ◽

2020 ◽

Vol 17 ◽

Author(s):

Akhlesh Kumar Jain ◽

Hitesh Sahu ◽

Keerti Mishra ◽

Suresh Thareja

Keyword(s):

Side Effects ◽

Liver Cancer ◽

Entrapment Efficiency ◽

Xrd Analysis ◽

In Vitro Cytotoxicity ◽

Physical Interaction ◽

Scanning Calorimetry ◽

Starch Nanoparticles

Aim: To design D-Mannose conjugated 5-Fluorouracil (5-FU) loaded Jackfruit seed starch nanoparticles (JFSSNPs) for site specific delivery. Background: Liver cancer is the third leading cause of death in world and fifth most often diagnosed cancer is the major global threat to public health. Treatment of liver cancer with conventional method bears several side effects, thus to undertake these side effects as a formulation challenge, it is necessary to develop novel target specific drug delivery system for the effective and better localization of drug into the proximity of target with restricting the movement of drug in normal tissues. Objective: To optimize and characterize the developed D-Mannose conjugated 5-Fluorouracil (5-FU) loaded Jackfruit seed starch nanoparticles (JFSSNPs) for effective treatment of liver cancer. Materials and methods: 5-FU loaded JFSSNPs were prepared and optimized formulation had higher encapsulation efficiency were conjugated with D-Mannose. These formulations were characterized for size, morphology, zeta potential, X-Ray Diffraction, and Differential Scanning Calorimetry. Potential of NPs were studied using in vitro cytotoxicity assay, in vivo kinetic studies and bio-distribution studies. Result and discussion: 5-Fluorouracil loaded NPs had particle size between 336 to 802nm with drug entrapment efficiency was between 64.2 to 82.3%. In XRD analysis, 5-FU peak was diminished in the diffractogram, which could be attributed to the successful incorporation of drug in amorphous form. DSC study suggests there was no physical interaction between 5- FU and Polymer. NPs showed sustained in vitro 5-FU release up to 2 hours. In vivo, mannose conjugated NPs prolonged the plasma level of 5-FU and assist selective accumulation of 5-FU in the liver (vs other organs spleen, kidney, lungs and heart) compared to unconjugated one and plain drug. Conclusion: In vivo, bio-distribution and plasma profile studies resulted in significantly higher concentration of 5- Fluorouracil liver suggesting that these carriers are efficient, viable, and targeted carrier of 5-FU treatment of liver cancer.

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High-throughput screening and rational design of biofunctionalized surfaces with optimized biocompatibility and antimicrobial activity

Nature Communications ◽

10.1038/s41467-021-23954-8 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Zhou Fang ◽

Junjian Chen ◽

Ye Zhu ◽

Guansong Hu ◽

Haoqian Xin ◽

...

Keyword(s):

Antimicrobial Activity ◽

High Throughput ◽

High Throughput Screening ◽

Rational Design ◽

Click Reaction ◽

Reaction Times ◽

Great Promise ◽

Biomaterial Surfaces

AbstractPeptides are widely used for surface modification to develop improved implants, such as cell adhesion RGD peptide and antimicrobial peptide (AMP). However, it is a daunting challenge to identify an optimized condition with the two peptides showing their intended activities and the parameters for reaching such a condition. Herein, we develop a high-throughput strategy, preparing titanium (Ti) surfaces with a gradient in peptide density by click reaction as a platform, to screen the positions with desired functions. Such positions are corresponding to optimized molecular parameters (peptide densities/ratios) and associated preparation parameters (reaction times/reactant concentrations). These parameters are then extracted to prepare nongradient mono- and dual-peptide functionalized Ti surfaces with desired biocompatibility or/and antimicrobial activity in vitro and in vivo. We also demonstrate this strategy could be extended to other materials. Here, we show that the high-throughput versatile strategy holds great promise for rational design and preparation of functional biomaterial surfaces.

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A molecular architectural design that promises potent antimicrobial activity against multidrug-resistant pathogens

NPG Asia Materials ◽

10.1038/s41427-021-00287-y ◽

2021 ◽

Vol 13 (1) ◽

Author(s):

Bing Yuan ◽

Jiaojiao Liu ◽

Zhixiong Deng ◽

Lin Wei ◽

Wenwen Li ◽

...

Keyword(s):

Architectural Design ◽

Building Blocks ◽

Multidrug Resistant ◽

In Vitro Cytotoxicity ◽

Antimicrobial Drugs ◽

Minimal Inhibitory Concentrations ◽

Antimicrobial Efficiency ◽

Multidrug Resistant Pathogens

AbstractAddressing the devastating threat of drug-resistant pathogens requires the discovery of new antibiotics with advanced action mechanisms and/or novel strategies for drug design. Herein, from a biophysical perspective, we design a class of synthetic antibacterial complexes with specialized architectures based on melittin (Mel), a natural antimicrobial peptide, and poly(ethylene glycol) (PEG), a clinically available agent, as building blocks that show potent and architecture-modulated antibacterial activity. Among the complexes, the flexibly linear complex consisting of one Mel terminally connected with a long-chained PEG (e.g., PEG12k–1*Mel) shows the most pronounced improvement in performance compared with pristine Mel, with up to 500% improvement in antimicrobial efficiency, excellent in vitro activity against multidrug-resistant pathogens (over a range of minimal inhibitory concentrations of 2–32 µg mL−1), a 68% decrease in in vitro cytotoxicity, and a 57% decrease in in vivo acute toxicity. A lipid-specific mode of action in membrane recognition and an accelerated “channel” effect in perforating the bacterial membrane of the complex are described. Our results introduce a new way to design highly efficient and low-toxicity antimicrobial drugs based on architectural modulations with clinically available agents.

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Akt kinase LANCL2 functions as a key driver in EGFR-mutant lung adenocarcinoma tumorigenesis

Cell Death and Disease ◽

10.1038/s41419-021-03439-8 ◽

2021 ◽

Vol 12 (2) ◽

Author(s):

Yuqing Lou ◽

Jianlin Xu ◽

Yanwei Zhang ◽

Wei Zhang ◽

Xueyan Zhang ◽

...

Keyword(s):

Lung Adenocarcinoma ◽

Cell Line ◽

Quantitative Polymerase Chain Reaction ◽

Mutant Cell ◽

A549 Cells ◽

The Cancer Genome Atlas ◽

Akt Kinase ◽

Egfr Expression

AbstractEpidermal growth factor receptor (EGFR) is a key oncogene in lung adenocarcinoma (LUAD). Resistance to EGFR tyrosine kinase inhibitors is a major obstacle for EGFR-mutant LUAD patients. Our gene chip array, quantitative polymerase chain reaction validation, and shRNA-based high-content screening identified the Akt kinase lanthionine synthetase C-like protein 2 (LANCL2) as a pro-proliferative gene in the EGFR-mutant LUAD cell line PC9. Therefore, we investigated whether LANCL2 plays a role in promoting cell proliferation and drug resistance in EGFR-mutant LUAD. In silico clinical correlation analysis using the Cancer Genome Atlas Lung Adenocarcinoma dataset revealed a positive correlation between LANCL2 and EGFR expression and an inverse relationship between LANCL2 gain-of-function and survival in LUAD patients. The EGFR-mutant LUAD cell lines PC9 and HCC827 displayed higher LANCL2 expression than the non-EGFR-mutant cell line A549. In addition, LANCL2 was downregulated following gefitinib+pemetrexed combination therapy in PC9 cells. LANCL2 knockdown reduced proliferation and enhanced apoptosis in PC9, HCC827, and A549 cells in vitro and suppressed murine PC9 xenograft tumor growth in vivo. Notably, LANCL2 overexpression rescued these effects and promoted gefitinib + pemetrexed resistance in PC9 and HCC827 cells. Pathway analysis and co-immunoprecipitation followed by mass spectrometry of differentially-expressed genes in LANCL2 knockdown cells revealed enrichment of several cancer signaling pathways. In addition, Filamin A and glutathione S-transferase Mu 3 were identified as two novel protein interactors of LANCL2. In conclusion, LANCL2 promotes tumorigenic proliferation, suppresses apoptosis, and promotes gefitinib+pemetrexed resistance in EGFR-mutant LUAD cells. Based on the positive association between LANCL2, EGFR, and downstream Akt signaling, LANCL2 may be a promising new therapeutic target for EGFR-mutant LUAD.

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