ABSTRACT
OBJECTIVE: To systematically evaluate the evidence relating to acupuncture on the sleep quality of patients with Parkinson's disease. DATA SOURCES: Six English-language (PubMed, Cochrane Library, EBSCOhost, Embase, OVID MEDLINE, and Web of Science) and four Chinese-language (China National Knowledge Infrastructure, SinoMed, China Scientific Journals Database, and Wanfang) databases were searched for pertinent studies published from database inception to 11 October 2023. METHODS: Two researchers independently screened eligible studies and extracted relevant data using custom data extraction tables. Methodological quality assessment of the included studies was performed using Cochrane Handbook 5.1.0. Meta-analysis was performed using Cochrane Review Manager version 5.4. RESULTS: Twenty-four studies (1701 participants) met inclusion criteria. The meta-analysis showed that acupuncture improved the Parkinson's Disease Sleep Scale, Pittsburgh Sleep Quality Index, Hamilton Anxiety Scale, Hamilton Depression Scale, Self-Rating Depression Scale, and Parkinson's Disease Questionnaire 39 scores compared with controls (all P < 0.05). CONCLUSION: This review showed that acupuncture improved sleep quality, anxiety and depressive symptoms, and quality of life of patients with Parkinson's disease relative to controls.
Subject(s)
Acupuncture Therapy , Parkinson Disease , Humans , Sleep Quality , Parkinson Disease/complications , Parkinson Disease/therapy , Quality of Life , AnxietyABSTRACT
Therapy resistance is responsible for most cancer-related death and is mediated by the unique ability of cancer cells to leverage metabolic conditions, signaling molecules, redox status, and other pathways for their survival. Interestingly, many cancer survival pathways are susceptible to disturbances in cellular reactive oxygen species (ROS) and may therefore be disrupted by exogenous ROS. Here, we explore whether trident cold atmospheric plasma (Tri-CAP), a gas discharge with exceptionally low-level ROS, could inhibit multiple cancer survival pathways together in a murine cell line model of therapy-resistant chronic myeloid leukemia (CML). We show that Tri-CAP simultaneously disrupts three cancer survival pathways of redox deregulation, glycolysis, and proliferative AKT/mTOR/HIF-1α signaling in this cancer model. Significantly, Tri-CAP blockade induces a very high rate of apoptotic death in CML cell lines and in primary CD34+ hematopoietic stem and progenitor cells from CML patients, both harboring the therapy-resistant T315I mutation. In contrast, nonmalignant controls are minimally affected by Tri-CAP, suggesting it selectively targets resistant cancer cells. We further demonstrate that Tri-CAP elicits similar lethality in human melanoma, breast cancer, and CML cells with disparate, resistant mechanisms and that it both reduces tumor formation in two mouse models and improves survival of tumor-bearing mice. For use in patients, administration of Tri-CAP may be extracorporeal for hematopoietic stem cell transplantation therapy, transdermal, or through its activated solution for infusion therapy. Collectively, our results suggest that Tri-CAP represents a potent strategy for disrupting cancer survival pathways and overcoming therapy resistance in a variety of malignancies.
Subject(s)
Leukemia, Experimental/therapy , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/therapy , Plasma Gases/therapeutic use , Animals , Carcinogenesis , Cell Line, Tumor , Humans , Lactic Acid/metabolism , Leukemia, Experimental/mortality , Mice , Oxidation-ReductionABSTRACT
A series of Ni(II) sandwich-like coordinated compounds were synthesized by the reaction of nickel dichloride and ten 4'-(4-substituent phenyl)-2',2':6',2â³-terpyridine ligands, and their structures were confirmed by elemental analysis, FT-IR, ESI-MS, solid state ultraviolet spectroscopy and X-ray single crystal diffraction analysis. Three human cancer cell lines and a normal human cell line were used for anti-proliferation potential study: human lung cancer cell line (A549), human esophageal cancer cell line (Eca-109), human liver cancer cells (Bel-7402) and normal human liver cells (HL-7702). The results show that these nickel complexes possess good inhibitory effects on the cancer cells, outperforming the commonly used clinical chemotherapy drug cisplatin. Especially, complexes 3 (-methoxyl) and 7 (-fluoro) have strong inhibitory ability against Eca-109 cell line with IC50 values of 0.223 µM and 0.335 µM, complexes 4 and 6 showed certain cell selectivity, and complex 6 can inhibit cancer cells and slightly poison normal cells when the concentration was controlled. The ability of these complexes binding to CT-DNA was studied by UV titration and CD spectroscopy, and CD spectroscopy was also used to study the secondary structural change of BSA under the action of the complexes. The binding of these complexes with DNA, DNA-Topo I and bovine serum protein has been simulated by molecular docking software, and the docking results and optimal binding conformation data showed that they interacted with DNA in the mode of embedded binding, which is consistent with the experimental results. These complexes are more inclined to move to the cleavage site when docking with DNA-Topo I, so as to play a role of enzyme cleavage, while BSA promotes the action of the complexes by binding to effective binding sites.
Subject(s)
Antineoplastic Agents , Coordination Complexes , Humans , Nickel/pharmacology , Nickel/chemistry , Molecular Docking Simulation , Ligands , Spectroscopy, Fourier Transform Infrared , DNA/chemistry , Coordination Complexes/chemistry , Antineoplastic Agents/chemistry , Serum Albumin, Bovine/metabolismABSTRACT
Through the study of biosorption of Pb2+ by lactic acid bacteria, two strains called CN-011 and CN-005 with high tolerance and great adsorption to lead were screened. The minimum bactericidal concentration of lead ions for both CN-011 and CN-005 was 1.45 mmol/L. The optimal culture conditions for the removal of 30 mg/L lead ions were achieved by culturing lactic acid bacteria at an initial pH of 7.0, 37 °C and 120 rpm for 48 h. The adsorption rate of CN-011 and CN-005 for Pb2+ were 85.95% and 86.78%, respectively. In simulated wastewater samples, the average adsorption rate of Pb2+ was 73.38% for CN-011 and 74.15% for CN-005. The mechanism of biosorption was characterized by Fourier Transform infrared spectroscopy, Scanning Electron Microscope-Energy Dispersive Spectrometer, X-ray Photoelectron Spectroscopy, which revealed that Pb2+ mainly reacted with hydroxyl ions in peptidoglycan or polysaccharide, and carboxylate radical in teichoic acid or protein on the surface of lactic acid bacteria cell wall. The deposits produced on the bacterial surface were identified as lead oxide and lead nitrate.
Subject(s)
Lactobacillales , Water Pollutants, Chemical , Wastewater , Lactobacillales/metabolism , Lead/metabolism , Hydrogen-Ion Concentration , Spectroscopy, Fourier Transform Infrared , Ions/metabolism , Kinetics , Water Pollutants, Chemical/analysis , BiomassABSTRACT
Our study aimed to systematically evaluate the effect of acupuncture in patients with obstructive sleep apnea-hypopnea syndrome (OSAHS). Literature search of four Chinese databases and six English databases for studies published from the inception of each database to March 1, 2022 and identify relevant studies published in Chinese or English. Related randomized controlled trials of acupuncture for the treatment of OSAHS were included to analyze the efficacy of acupuncture. Two researchers independently reviewed all of the retrieved studies to screen for eligible studies and extract the required relevant data. Included studies were subjected to a methodological quality assessment using the Cochrane Manual 5.1.0, and to a meta-analysis using Cochrane Review Manager version 5.4. A total of 19 studies with 1365 participants were examined. Compared with the control group, the apnea-hypopnea index, lowest oxygen saturation, Epworth Sleepiness Scale, interleukin-6, tumor necrosis factor α, and nuclear factor κ-B indicators all exhibited statistically significant changes. Thus, acupuncture was effective in alleviating the state of hypoxia and sleepiness and reduced the inflammatory response and disease severity among reported patients with OSAHS. Therefore, acupuncture could be widely used in the clinical treatment of OSAHS patients as a complementary strategy and warrants further study.
Subject(s)
Acupuncture Therapy , Sleep Apnea, Obstructive , Humans , Sleepiness , Sleep Apnea, Obstructive/therapy , SyndromeABSTRACT
The low detection sensitivity of lateral-flow immunochromatography assay (LFIA) based on spherical gold nanoparticle (AuNP) limits its wide applications. In the present study, AuNP dimers with strong plasma scattering and robust signal output were synthesized via the Ag ion soldering (AIS) strategy and used as labeled probes in LFIA to boost the sensitivity without any extra operation process and equipment. The established LFIA exhibited high sensitivity with a limit of detection (LOD) of 2.0 × 102 TCID50/mL for PEDV, which provides 50 times higher sensitivity than commercial LFIA based on spherical colloidal gold. In addition, the AuNP dimer-based LFIA showed strong specificity, good reproducibility, high stability, and good accordance to reverse transcription polymer chain reaction (RT-PCR) when detecting 109 clinical samples. Thus, the AuNP dimers is a promising probe for LFIA and the developed AuNP dimer-based LFIA is suitable for the rapid detection of PEDV in the field.
Subject(s)
Metal Nanoparticles , Porcine epidemic diarrhea virus , Swine Diseases , Animals , Swine , Gold , Sensitivity and Specificity , Reproducibility of Results , Swine Diseases/diagnosis , Metal Nanoparticles/chemistry , Chromatography, Affinity , PolymersABSTRACT
Eleven manganese 4'-substituted-2,2':6',2â³-terpyridine complexes (1a-1c and 2a-2h) with three non-oxygen-containing substituents (L1a-L1c: phenyl, naphthalen-2-yl and naphthalen-1-yl, L1a-L1c) and eight oxygen-containing substituents (L2a-L2h: 4-hydroxyl-phenyl, 3-hydroxyl-phenyl, 2-hydroxyl-phenyl, 4-methoxyl-phenyl, 4-carboxyl-phenyl, 4-(methylsulfonyl)phenyl, 4-nitrophenyl and furan-2-yl) were prepared and characterized by IR, elemental analysis or single crystal X-ray diffraction. In vitro data demonstrate that all of these show higher antiproliferative activities than cisplatin against five human carcinoma cell lines: A549, Bel-7402, Eca-109, HeLa and MCF-7. Compound 2d presents the strongest antiproliferative effect against A549 and HeLa cells, with IC50 values being 0.281 µM and 0.356 µM, respectively. The lowest IC50 values against Bel-7402 (0.523 µM) Eca-109 (0.514 µM) and MCF-7 (0.356 µM) were obtained for compounds 2h, 2g and 2c, respectively. Compound 2g with a nitro group showed the best results on the whole, with relevantly low IC50 values against all the tested tumor cells. The DNA interactions with these compounds were studied by circular dichroism spectroscopic and molecular modeling methods. Spectrophotometric results revealed that the compounds have strong affinities in binding with DNA as intercalators, and the binding induces DNA conformational transition. Molecular docking studies indicate that the binding is contributed by the π-π stacking and hydrogen bonds. The anticancer activities of the compounds are correlated with their DNA binding ability, and the modification of oxygen-containing substituents significantly enhanced the anticancer activity, which could provide a new rationale for the future design of terpyridine-based metal complexes with antitumor potential.
Subject(s)
Antineoplastic Agents , Coordination Complexes , Humans , HeLa Cells , Antineoplastic Agents/pharmacology , Molecular Docking Simulation , Manganese/pharmacology , Oxygen/pharmacology , Coordination Complexes/pharmacology , DNA/chemistry , Cell Line, Tumor , Cell ProliferationABSTRACT
Using STAT3 inhibitors as a potential strategy in cancer therapy have attracted much attention. Recently, celastrol has been reported that it could directly bind to and suppress the activity of STAT3 in the cardiac dysfunction model. To explore more effective STAT3 inhibiting anti-tumour drug candidates, we synthesised a series of celastrol derivatives and biologically evaluated them with several human cancer cell lines. The western blotting analysis showed that compound 4 m, the most active derivative, could suppress the STAT3's phosphorylation as well as its downstream genes. SPR analysis, molecular docking and dynamics simulations' results indicated that the 4m could bind with STAT3 protein more tightly than celastrol. Then we found that the 4m could block cell-cycle and induce apoptosis on HCT-116 cells. Furthermore, the anti-tumour effect of 4m was verified on colorectal cancer organoid. This is the first research that discovered effective STAT3 inhibitors as potent anti-tumour agents from celastrol derivatives.
Subject(s)
Antineoplastic Agents/pharmacology , Pentacyclic Triterpenes/pharmacology , STAT3 Transcription Factor/antagonists & inhibitors , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Apoptosis/drug effects , Cell Cycle/drug effects , Cell Proliferation/drug effects , Dose-Response Relationship, Drug , Drug Screening Assays, Antitumor , Humans , Models, Molecular , Molecular Structure , Pentacyclic Triterpenes/chemical synthesis , Pentacyclic Triterpenes/chemistry , STAT3 Transcription Factor/metabolism , Structure-Activity Relationship , Tumor Cells, CulturedABSTRACT
With the rapid development of biomaterials and biotechnologies, various functional materials-based drug delivery systems (DDS) are developed to overcome the limitations of traditional drug release formulations, such as uncontrollable drug concentration in target organs/tissues and unavoidable adverse reactions. Polymer nanofibers exhibit promising characteristics including easy preparation, adjustable features of wettability and elasticity, tailored surface and interface properties, and surface-to-volume ratio, and are used to develop new DDS. Different kinds of drugs can be incorporated into the polymer nanofibers. Additionally, their release kinetics can be modulated via the preparation components, component proportions, and preparation processes, enabling their applications in several fields. A timely and comprehensive summary of polymeric nanofibers for DDS is thus highly needed. This review first describes the common methods for polymer nanofiber fabrication, followed by introducing controlled techniques for drug loading into and release from polymer nanofibers. Thus, the applications of polymer nanofibers in drug delivery were summarized, particularly focusing on the relation between the physiochemical properties of polymeric nanofibers and their DDS performance. It is ended by listing future perspectives. Graphical abstract.
Subject(s)
Nanofibers , Polymers , Drug Delivery Systems , Biocompatible Materials , WettabilityABSTRACT
SARS-CoV-2 is a highly contagious virus and is causing a global pandemic. SARS-CoV-2 infection depends on the recognition of and binding to the cellular receptor human angiotensin-converting enzyme 2 (hACE2) through the receptor-binding domain (RBD) of the spike protein, and disruption of this process can effectively inhibit SARS-CoV-2 invasion. Plasma-activated water efficiently inactivates bacteria and bacteriophages by causing damage to biological macromolecules, but its effect on coronavirus has not been reported. In this study, pseudoviruses with the SARS-CoV-2 S protein were used as a model, and plasma-activated water (PAW) effectively inhibited pseudovirus infection through S protein inactivation. The RBD was used to study the molecular details, and the RBD binding activity was inactivated by plasma-activated water through the RBD modification. The short-lived reactive species in the PAW, such as ONOO-, played crucial roles in this inactivation. Plasma-activated water after room-temperature storage of 30 days remained capable of significantly reducing the RBD binding with hACE2. Together, our findings provide evidence of a potent disinfection strategy to combat the epidemic caused by SARS-CoV-2.
ABSTRACT
A surface-enhanced Raman scattering (SERS) immunochromatographic assay (ICA) has been developed for rapid, ultrasensitive, and quantitative detection of rotavirus in feces using double Raman molecule-labeled Au-core Ag-shell nanoparticles. The Raman signals are generated by 5,5'-dithiobis-(2-nitrobenzoic acid) and the intensity of the characteristic peak at 1334-1 cm was detected as the analytical signal. The Raman signals were enhanced by the SERS-enhanced effect of both Au and Ag, the large amount of Raman molecules, and the hot-spot effect in the narrow gap between the Au core and Ag shell. The SERS ICA can quantitatively detect rotavirus in a concentration range of 8- 40,000 pg/mL, with detection limits of 80 pg/mL and 8 pg/mL based on naked eye observation and SERS signal detection, respectively. No cross-reaction was observed from other common pathogens. The standard deviation of the intra- and inter-batch repetitive tests is less than 10%, and the coincidence between SERS ICA and RT-qPCR as well as commercial colloidal gold ICA is 100%. The results indicated that this SERS ICA is able to quantitatively detect rotavirus in feces in 20 min with high sensitivity, selectivity, reproducibility, and accuracy and might be a promising method for the early detection of rotavirus in clinical analysis.
Subject(s)
Chromatography, Affinity/methods , Metal Nanoparticles/chemistry , Rotavirus/isolation & purification , Spectrum Analysis, Raman/methods , Antibodies, Immobilized/immunology , Antibodies, Monoclonal, Murine-Derived/immunology , Dithionitrobenzoic Acid/chemistry , Feces/virology , Gold/chemistry , Humans , Limit of Detection , Reproducibility of Results , Rotavirus/immunology , Silver/chemistryABSTRACT
Six zinc(II) complexes, [Zn(OCOPh)2LR] (R = 1, 2, 3, 4, 5, 6) were synthesized by the reaction of zinc benzoate and six para-substituted 4-phenyl-terpyridine complexes and their structures were confirmed by elemental analysis, FT-IR, 1H NMR and X-ray single crystal diffraction analysis. Their photoluminescent properties in solid and in solutions of DMSO were studied. Three human cancer cell lines were used for antiproliferative potential: human lung cancer cell line (A549), human esophageal cancer cell line (Eca-109) and human breast cancer cell line (MCF-7). The results have shown that these zinc complexes have good inhibitory effects on cancer cells, which are better than that of the commonly used clinical drug cisplatin. The ability of the complexes to binding to CT-DNA was studied by UV spectroscopy and fluorescence titration, while the interaction between the complexes and CT-DNA, AT6, GC6 short-chain DNA sequences and G-quadruplex were analyzed by circular dichroism (CD). It is found that these complexes can bind to DNA, and the binding mode is mainly intercalator. The docking of the complexes with the DNA fragment was simulated using molecular docking software. All the results clearly display that the substituents at these ligands of the complexes have the substitution effects on the properties of photoluminescence, antiproliferative potential and DNA binding study.
Subject(s)
Antineoplastic Agents/pharmacology , Benzoates/pharmacology , Coordination Complexes/pharmacology , DNA/chemistry , Pyridines/pharmacology , Zinc/pharmacology , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Benzoates/chemistry , Binding Sites/drug effects , Cell Line, Tumor , Cell Proliferation/drug effects , Cell Survival/drug effects , Coordination Complexes/chemical synthesis , Coordination Complexes/chemistry , Crystallography, X-Ray , Drug Screening Assays, Antitumor , Humans , Models, Molecular , Molecular Structure , Pyridines/chemistry , Zinc/chemistryABSTRACT
Tandem whole-cell biotransformation was applied successfully to deliver novel pentacyclic triterpenoid derivatives for the first time. In this process, the starting substrate oleanolic acid (1) was biotransformed into a hydroxylated metabolite 1a by Rhizopus chinensis CICC 40335 and then was further glycosylated to 1b by Bacillus subtilis ATCC 6633. Moreover, metabolite 1a was furtherly oxidized by Streptomyces griseus ATCC 13273 and generated two new derivatives as 1c and 1d. To validate the feasibility, tandem biotransformation of 18ß-glycyrrhetinic acid (2) by R. chinensis and B. subtilis was also conducted and offered a glycosylated derivative (2c). Finally, the neuroprotective effects of the derivatives were assessed on neural injury PC12 cell model induced by cobalt chloride.
Subject(s)
Neuroprotective Agents/metabolism , Triterpenes/chemistry , Animals , Bacillus subtilis/metabolism , Cobalt/toxicity , Glycosylation , Glycyrrhetinic Acid/analogs & derivatives , Glycyrrhetinic Acid/chemistry , Glycyrrhetinic Acid/metabolism , Molecular Conformation , Neurons/drug effects , Neurons/metabolism , Neuroprotective Agents/chemistry , Neuroprotective Agents/pharmacology , Oleanolic Acid/chemistry , Oleanolic Acid/metabolism , PC12 Cells , Rats , Rhizopus/metabolism , Streptomyces/metabolism , Triterpenes/metabolism , Triterpenes/pharmacologyABSTRACT
In this study, seven 30-norlupane derivatives (2-8) wasobtained from the chemical oxidation ofbetulinic acidfollowed bybiotransformationviaBacillus megateriumCGMCC 1.1741. And metabolites 2-4 and 6-8 were newly identified products. In the first step, betulinic acid was chemically oxidizedto platanic acid (1). Following the chemical oxidation, B. megaterium catalyzed the hydroxylation at C-7, C-11, C-15 and C-23 of platanic acid (1) as well as the oxidation of C-3 hydroxyl group. Compared to the labor-intensive isolation from natural plants, this chemical-microbial semi-synthesis is more capable to provide increased structural diversity of oxygenated 30-norlupane. Finally, the potential neuroprotective effect of the derivatives was assessed on neuron-like PC12 cells induced by cobalt chloride (CoCl2). Metabolite 6 showed a potent neuroprotective activity.
Subject(s)
Neuroprotective Agents/chemistry , Pentacyclic Triterpenes/chemistry , Animals , Bacillus megaterium/chemistry , Bacillus megaterium/metabolism , Biotransformation , Cell Survival/drug effects , Cobalt/toxicity , Hydroxylation , Magnetic Resonance Spectroscopy , Mass Spectrometry , Molecular Conformation , Neurons/cytology , Neurons/drug effects , Neurons/metabolism , Neuroprotective Agents/metabolism , Neuroprotective Agents/pharmacology , Oxidation-Reduction , PC12 Cells , Pentacyclic Triterpenes/chemical synthesis , Pentacyclic Triterpenes/metabolism , Pentacyclic Triterpenes/pharmacology , Rats , Betulinic AcidABSTRACT
BACKGROUND: Acute myeloid leukemia (AML) is a typically fatal malignancy and new drug and treatment need to be developed for a better survival outcome. Cold atmospheric plasma (CAP) is a novel technology, which has been widely applied in biomedicine, especially in various of cancer treatment. However, the changes in cell metabolism after CAP treatment of leukemia cells have been rarely studied. METHODS: In this study, we investigated the metabolite profiling of plasma treatment on leukemia cells based on Gas Chromatography Tandem Time-of-Flight Mass Spectrometry (GC-TOFMS). Simultaneously, we conducted a series of bioinformatics analysis of metabolites and metabolic pathways with significant differences after basic data analysis. RESULTS: 800 signals were detected by GC-TOF mass-spectrometry and then evaluated using PCA and OPLS-DA. All the differential metabolites were listed and the related metabolic pathways were analyzed by KEGG pathway. The results showed that alanine, aspartate and glutamate metabolism had a significant change after plasma treatment. Meanwhile, d-glutamine and d-glutamate metabolism were significantly changed by CAP. Glutaminase activity was decreased after plasma treatment, which might lead to glutamine accumulation and leukemia cells death. CONCLUSIONS: We found the above two metabolic pathways vulnerable to plasma treatment, which might result in leukemia cells death and might be the cornerstone of further exploration of plasma treatment targets.
ABSTRACT
BACKGROUND AND AIMS: It has been increasingly recognized that the safety of GI endoscopes needs to be improved by addressing the small margin of safety of high-level disinfectants (HLDs) and the failure of HLDs to clear multidrug-resistant organisms and biofilms. There is also an unmet need for effective low-temperature sterilization techniques that have a clear pathway for U.S. Food and Drug Administration clearance. Here, we report the results of our investigation of a novel argon plasma-activated gas (PAG) for disinfection and potentially sterilization of biofilm-contaminated endoscopic channels. METHODS: Test polytetrafluoroethylene channel segments were contaminated with 4-, 24- and 48-hour luminal biofilms of methicillin-resistant Staphylococcus aureus, Pseudomonas aeruginosa, or Escherichia coli and were treated by PAG flowing for up to 9 minutes. After PAG treatment, inactivation and dispersal of luminal bacterial biofilms and their regrowth in 48 hours were evaluated. Reactive species induced by PAG were measured with colorimetric probes and electron spin resonance spectrometry. Surface morphology and elemental composition of PAG-treated channel material were analyzed with scanning electron microscopy. RESULTS: PAG treatment for 9 minutes led to more than 8 log reduction of viable cells and dispersal of 24- and 48-hour luminal biofilms of all 3 bacteria and to suppression of their regrowth, whereas it resulted in little morphologic abnormalities in channel material. Ozone concentration of PAG fell to below .01 ppm within 30 seconds of switching off the plasma. PAG-treated deionized water was acidified with numerous types of reactive species, each with a concentration some 3 orders of magnitude or more below its bacterial inhibition concentration. CONCLUSIONS: PAG is capable of effectively and rapidly disinfecting luminal bacterial biofilms and offers an alternative to the step of HLDs and/or ethylene oxide in the endoscope reprocessing procedure with safety to personnel and environment.
Subject(s)
Argon/pharmacology , Biofilms/drug effects , Endoscopes, Gastrointestinal/microbiology , Equipment Contamination , Escherichia coli/drug effects , Methicillin-Resistant Staphylococcus aureus/drug effects , Pseudomonas aeruginosa/drug effects , Disinfection/methods , Electron Spin Resonance Spectroscopy , Escherichia coli/ultrastructure , Humans , Methicillin-Resistant Staphylococcus aureus/ultrastructure , Microscopy, Electron, Scanning , Pseudomonas aeruginosa/ultrastructure , Reactive Nitrogen Species/metabolism , Reactive Oxygen Species/metabolismABSTRACT
A series of ZnCl2 complexes (compounds 1-10) with 4'-(substituted-phenyl)-2,2':6',2''-terpyridine that bears hydrogen (L1), p-methyl (L2), p-methoxy (L3), p-phenyl (L4), p-tolyl (L5), p-hydroxyl (L6), m-hydroxyl (L7), o-hydroxyl (L8), p-carboxyl (L9), or p-methylsulfonyl (L10) were prepared and then characterized by 1H NMR, electrospray mass-spectra (ESI-MS), IR, elemental analysis, and single crystal X-ray diffraction. In vitro cytotoxicity assay was used to monitor the antiproliferative activities against tumor cells. Absorption spectroscopy, fluorescence titration, circular dichroism spectroscopy, and molecular modeling studied the DNA interactions. All of the compounds display interesting photoluminescent properties and different maximal emission peaks due to the difference of the substituent groups. The cell viability studies indicate that the compounds have excellent antiproliferative activity against four human carcinoma cell lines, A549, Bel-7402, MCF-7, and Eca-109, with the lowest IC50 values of 0.33 (10), 0.66 (6), 0.37 (7), and 1.05 (7) µM, respectively. The spectrophotometric results reveal that the compounds have strong affinity binding with DNA as intercalator and induce DNA conformational transition. Molecular docking studies indicate that the binding is contributed by the π π stacking and hydrogen bonds, providing an order of nucleotide sequence binding selectivity as ATGC > ATAT > GCGC. These compounds intercalate into the base pairs of the DNA of the tumor cells to affect their replication and transcription, and the process is supposed to play an important role in the anticancer mechanism.
Subject(s)
Coordination Complexes/chemistry , Coordination Complexes/pharmacology , Pyridines/chemistry , Zinc/chemistry , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Cell Line, Tumor , Cell Survival/drug effects , Crystallography, X-Ray , DNA/chemistry , Dose-Response Relationship, Drug , Humans , Intercalating Agents/chemistry , Intercalating Agents/pharmacology , Models, Molecular , Structure-Activity RelationshipABSTRACT
Antimicrobial lock solutions are important for prevention of microbial colonization and infection of long-term central venous catheters. We investigated the efficacy and safety of a novel antibiotic-free lock solution formed from gas plasma-activated disinfectant (PAD). Using a luminal biofilm model, viable cells of methicillin-resistant Staphylococcus aureus, Staphylococcus epidermidis, Pseudomonas aeruginosa, and Candida albicans in mature biofilms were reduced by 6 to 8 orders of magnitude with a PAD lock for 60 min. Subsequent 24-h incubation of PAD-treated samples resulted in no detectable regrowth of viable bacteria or fungi. As a comparison, the use of a minocycline-EDTA-ethanol lock solution for 60 min led to regrowth of bacteria and fungi, up to 107 to 109 CFU/ml, in 24 h. The PAD lock solution had minimal impact on human umbilical vein endothelial cell viability, whereas the minocycline-EDTA-ethanol solution elicited cell death in nearly half of human endothelial cells. Additionally, PAD treatment caused little topological change to catheter materials. In conclusion, PAD represents a novel antibiotic-free, noncytotoxic lock solution that elicits rapid and broad-spectrum eradication of biofilm-laden microbes and shows promise for the prevention and treatment of intravascular catheter infections.
Subject(s)
Anti-Infective Agents/adverse effects , Anti-Infective Agents/pharmacology , Biofilms/drug effects , Candida albicans/drug effects , Cell Survival/drug effects , Endothelial Cells/drug effects , Humans , Microbial Sensitivity Tests , Pseudomonas aeruginosa/drug effects , Staphylococcus epidermidis/drug effectsABSTRACT
Viruses cause serious pathogenic contamination that severely affects the environment and human health. Cold atmospheric-pressure plasma efficiently inactivates pathogenic bacteria; however, the mechanism of virus inactivation by plasma is not fully understood. In this study, surface plasma in argon mixed with 1% air and plasma-activated water was used to treat water containing bacteriophages. Both agents efficiently inactivated bacteriophages T4, Φ174, and MS2 in a time-dependent manner. Prolonged storage had marginal effects on the antiviral activity of plasma-activated water. DNA and protein analysis revealed that the reactive species generated by plasma damaged both nucleic acids and proteins, consistent with the morphological examination showing that plasma treatment caused the aggregation of bacteriophages. The inactivation of bacteriophages was alleviated by the singlet oxygen scavengers, demonstrating that singlet oxygen played a primary role in this process. Our findings provide a potentially effective disinfecting strategy to combat the environmental viruses using cold atmospheric-pressure plasma and plasma-activated water.IMPORTANCE Contamination with pathogenic and infectious viruses severely threatens human health and animal husbandry. Current methods for disinfection have different disadvantages, such as inconvenience and contamination of disinfection by-products (e.g., chlorine disinfection). In this study, atmospheric surface plasma in argon mixed with air and plasma-activated water was found to efficiently inactivate bacteriophages, and plasma-activated water still had strong antiviral activity after prolonged storage. Furthermore, it was shown that bacteriophage inactivation was associated with damage to nucleic acids and proteins by singlet oxygen. An understanding of the biological effects of plasma-based treatment is useful to inform the development of plasma into a novel disinfecting strategy with convenience and no by-product.
Subject(s)
Argon/pharmacology , Bacteriophage T4/drug effects , Disinfection/methods , Levivirus/drug effects , Plasma Gases/pharmacology , Virus Inactivation/drug effects , Nucleic Acids/chemistry , Singlet Oxygen/chemistry , Viral Proteins/chemistryABSTRACT
BACKGROUND: Despite new progress of chemotherapy in multiple myeloma (MM) clinical treatment, MM is still a refractory disease and new technology is needed to improve the outcomes and prolong the survival. Cold atmospheric plasma is a rapidly developed technology in recent years, which has been widely applied in biomedicine. Although plasma could efficiently inactivate various tumor cells, the effects of plasma on tumor cell metabolism have not been studied yet. METHODS: In this study, we investigated the metabolite profiling of He plasma treatment on myeloma tumor cells by gas-chromatography time-of-flight (GC-TOF) mass-spectrometry. Meanwhile, by bioinformatic analysis such as GO and KEGG analysis we try to figure out the metabolism pathway that was significantly affected by gas plasma treatment. RESULTS: By GC-TOF mass-spectrometry, 573 signals were detected and evaluated using PCA and OPLS-DA. By KEGG analysis we listed all the differential metabolites and further classified into different metabolic pathways. The results showed that beta-alanine metabolism pathway was the most significant change after He gas plasma treatment in myeloma cells. Besides, propanoate metabolism and linoleic acid metabolism should also be concerned during gas plasma treatment of cancer cells. CONCLUSIONS: Cold atmospheric plasma treatment could significantly alter the metabolite profiling of myeloma tumor cells, among which, the beta-alanine metabolism pathway is the most susceptible to He gas plasma treatment.