Inhibition Of Dehydrogenase Activity Research Articles

Plasmodium falciparum Lactate Dehydrogenase Inhibitory Activities of Pomegranate and Mangosteen Extracts and their Major Constituents

Plasmodium falciparum Lactate Dehydrogenase Inhibitory Activities of Pomegranate and Mangosteen Extracts and their Major Constituents

Targeting macrophagic 17β-HSD7 by fenretinide for the treatment of nonalcoholic fatty liver disease

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide and macrophage polarization plays an important role in its pathogenesis. However, which molecule regulates macrophage polarization in NAFLD remains unclear. Herein, we showed NAFLD mice exhibited increased 17β-hydroxysteroid dehydrogenase type 7 (17β-HSD7) expression in hepatic macrophages concomitantly with elevated M1 polarization. Single-cell RNA sequencing on hepatic non-parenchymal cells isolated from wild-type littermates and macrophage-17β-HSD7 knockout mice fed with high fat diet (HFD) for 6 weeks revealed that lipid metabolism pathways were notably changed. Furthermore, 17β-HSD7 deficiency in macrophages attenuated HFD-induced hepatic steatosis, insulin resistance and liver injury. Mechanistically, 17β-HSD7 triggered NLRP3 inflammasome activation by increasing free cholesterol content, thereby promoting M1 polarization of macrophages and the secretion of pro-inflammatory cytokines. In addition, to help demonstrate that 17β-HSD7 is a potential drug target for NAFLD, fenretinide was screened out from an FDA-approved drug library based on its 17β-HSD7 dehydrogenase inhibitory activity. Fenretinide dose-dependently abrogated macrophage polarization and pro-inflammatory cytokines production, and subsequently inhibited fat deposition in hepatocytes co-cultured with macrophages. In conclusion, our findings suggest that blockade of 17β-HSD7 signaling by fenretinide would be a drug repurposing strategy for NAFLD treatment.

Synthesis and Structure-activity Relationship Study of 2,4-dioxothiazolidin-5-ylidene Derivatives for 15-hydroxyprostaglandin Dehydrogenase Inhibitory Activity, Prostaglandin E2 Release, and Wound Healing Effect

Synthesis and Structure-activity Relationship Study of 2,4-dioxothiazolidin-5-ylidene Derivatives for 15-hydroxyprostaglandin Dehydrogenase Inhibitory Activity, Prostaglandin E2 Release, and Wound Healing Effect

Ecological response to antibiotics re-entering the aquaculture environment with possible long-term antibiotics selection based on enzyme activity in sediment.

Antibiotics are frequently applied in aquaculture to control infectious diseases and promote aquaculture production. The long-term application of antibiotics can lead to antibiotic resistance within an ecosystem. Herein, we assessed the ecological responses to two antibiotics (oxytetracycline (OTC) and sulfadiazine (SD)) at three concentrations (0mg/kg (control), 10mg/kg, and 1000mg/kg) re-entering the aquaculture sediments of shrimp ponds with an approximately long-term drug application history (5, 15, and more than 30years) for 2 and 4months. For the newly reclaimed aquaculture ponds (approximately 5years), the re-entered OTC significantly promoted urease activity (UA) and peroxidase activity (POA), while inhibited dehydrogenase activity (DHA) and fluorescein diacetate esterase activity (FDA). Meanwhile, the re-entered SD showed promotional effects on POA and DHA, and inhibitory effects on UA and FDA. For ponds with 15years of aquaculture history, re-entered OTC promoted POA, inhibited FDA, and changed the influencing effects of UA and DHA with exposure time. The re-entered SD showed promotional effects on UA, POA and DHA, and inhibitory effects on FDA. For long-term aquaculture ponds (more than 30years of aquaculture history), re-entered OTC promoted POA, DHA, and FDA, while it inhibited UA. Meanwhile, SD promoted all four enzyme activities. Pearson correlation analysis indicated that the variances of enzyme responses to the re-entry of antibiotics in the three sediment environments were related with the type, concentration, and exposure time of antibiotics, as well as the sediment properties and aquaculture history. The enzyme activities in the sediment environment from newly reclaimed aquaculture ponds were more sensitive to the re-entered antibiotics, while the enzyme activities displayed a clear tolerance in the sediment environment with more than 30years of aquaculture history. However, in the sediment environment with 15years of aquaculture history, the response of the enzyme activities to re-entered antibiotics demonstrated time processes of antibiotic adaptation during antibiotic resistance selection. This study has illustrated the effects of re-entered antibiotics on enzyme activities in the aquaculture environment with long-term antibiotic resistance/tolerance profiles, and further establishes the possible effects on ecosystem functioning in continuous antibiotic selection pressure.

Inhibitory Effects of Ternary Mixtures of Sodium Dodecyl Sulfate and Heavy Metals to Acinetobacter seifertii from Otamiri River Sediment in Southeastern Nigeria

Toxicities of sodium dodecyl sulfate (SDS) and heavy metals, Pb(II), Cd(II), Ni(II), Zn(II) and Co(II), as individuals and ternary mixtures of two heavy metals and SDS to Acinetobacter seifertii isolated as preponderant bacterium from Otamiri river sediment, were assessed, using inhibition of dehydrogenase activity as end point. Among the individual toxicants, the EC50S observed ranged from 0.011 ± 0.000 mM for Cd(II) to 2.810 ± 0.140 mM for SDS. The EC50S of the toxicants were statistically different from one another and the order of increasing toxicities were SDS > Ni(II) > Pb(II) > Zn(II) > Co(II) >Cd(II). The responses of the bacterium were concentration -dependent. Arbitrary (ABCR) and EC50 equieffect (EECR) fixed ratio mixtures were used to evaluate the combined toxicities of the toxicants. The concentration-response relationships of all mixtures and individual toxicants were sigmoidal and fitted with logistic function. The observed toxicities (EC50S) were compared with toxicities predicted from concentration addition (CA) and independent action (IA) models. In ABCR1 and ABCR3 mixture ratios of SDS+Ni(II)+Cd(II) and SDS+Co(II)+Cd(II) ternary mixtures, both CA- and IA-predicted EC50S were not statistically different from each other. Furthermore, in all ternary mixtures, both models underestimated the mixture toxicities to A. seifertii, except in ABCR1 of SDS+Ni(II)+Cd(II) mixture, where both models almost correctly predicted the toxicities. Basically, synergistic interaction of the mixture components observed against A. seifertii, indicates their possible toxicological effects on the bacterial population of the aquatic ecosystems.

Assessing the toxicities of the binary mixtures of sodium dodecyl sulfate and heavy metals to Serratia marcescens (SerEW01) from Otamiri River

Toxicities of sodium dodecyl sulfate (SDS) + Pb(II), SDS + Cd(II), SDS + Ni(II), SDS + Zn(II), and SDS + Co(II) binary mixtures to Serratia marcescens (SerEW01) isolated from Otamiri river water, Owerri, Imo State, Nigeria were undertaken, using dehydrogenase activity as a response. Inhibitions of dehydrogenase activity by the individual toxicants were concentrationdependent, increasing steadily as the concentration increases. The observed EC50S ranged from 0.046 ± 0.003 mM for Zn(II) to 2.329 ± 0.092 mM for SDS. Duncan tests indicated that the EC50S of the individual toxicants differed significantly from each other. The order of decreasing toxicities was Zn(II) > Cd(II) > Co(II) > Ni(II) > Pb(II) > SDS. Fixed ratio mixtures [Arbitrary concentration ratio (ABCR) and EC50 equieffect concentration ratio (EECR 50)] were used to study the joint action of the binary mixtures. The mixtures progressively inhibited dehydrogenase activity in S. marcescens as the concentration increases. However, SDS 98.08% + Co(II) 1.92% mixture ratio was biphasic. The effects of the mixtures on the dehydrogenase activity were assessed using Toxic Index, Model Deviation Ratio and Isobolographic analyses. In addition, the toxicities of the mixtures were predicted with concentration addition (CA) and independent action (IA) models. In SDS+Ni(II) binary mixture, both models predicted similar toxicities. In all binary mixtures, both models greatly underestimated the mixture toxicities compared to the experimentally-observed data. Similarly, both the experimentally-observed, CA and IA-predicted EC50S were statistically different from each another. Furthermore, the binary mixtures were generally synergistic against S. marcescens (SerEW01). This demonstrates the potential danger of co-contamination of the aquatic system by SDS and heavy metals

Synergistic Toxicity of Phenols and Cadmium Ion Binary Mixtures on Bacillus Sp and Pseudomonas Sp

Toxicity of Cadmium (Cd), 4-chlorophenol (4-CP), and 2,4-dichlorophenol (2,4-DCP) as single compounds and binary mixtures on Bacillus sp and Pseudomonas sp isolated from garden soil was assessed using inhibition of total dehydrogenase as toxicity response. Binary mixtures of metal and chlorophenol were composed using arbitrary concentration ratios (%) corresponding to metal/phenol mixtures of 20/80; 40/60; 50/50 and 30/70; 45/55, 50/50 for the chemical pairs: Cd/4-CP and Cd/2,4-DCP respectively. Results obtained showed that the binary mixtures of Cd/4-CP and Cd/2,4-DCP all exhibited a dose-dependent inhibition of dehydrogenase activity in the test isolates. The binary mixture of CD/4-CP exhibited higher toxicity in ratio 40/60 and 20/80 for the isolates Bacillus sp and Pseudomonas sp with IC50 values of 0.212±0.002 and 0.158± 0.008mM respectively. While for the mixture of Cd/2,4-DCP, toxicity was highest at the 50/50 and 45/55 ratio for Bacillus sp and Pseudomonas sp with IC50 values of 0.069±0.001mM and 0.068±0.001mM respectively. The binary mixtures of the chemicals evaluated showed a progressive inhibition of dehydrogenase activity with Pseudomonas sp showing a higher susceptibility. Isobolographic analysis of binary mixture interaction against Bacillus sp and Pseudomonas sp showed largely synergistic interactions. The combination of Cd with the chlorophenols resulted in a synergistic increase in the toxicity of the compounds to the test isolates. The toxicity of Cd/4-CP binary mixture ratios to dehydrogenase activity of Bacillus sp and Pseudomonas sp was in the order 40:60>50:50>20:80 and 20:80>50:50>40:60 respectively; similarly that of Cd/2,4-DCP mixtures were 50:50>45:55>30:70 and 45:55>50:50>30:70 for Bacillus and Pseudomonas sp respectively. The trend and implications of the toxicity interactions are further discussed.

In vitro Interactive Toxicity of Binary Mixtures of Selected Herbicides on Lysinibacillusfusiformis

Aims: To assess the toxicities of some herbicides as individuals and in binary mixtures to Lysinibacillus fusiformis isolated from Oryzasativa plant using dehydrogenase activity as an endpoint.
 Study Design: The binary mixture consists of combination of any two herbicides selected from the three herbicides (drysate, weedcut and aminoforce) for the study The binary mixture ratios (%) were designed as: 50%:50%; 80%:20% and 20%:80% for the respective mixtures in the concentration range of 0 -10, 000 mg/L.
 Place and Duration of Study: Silver Press Laboratory, Owerri Nigeria between July, 2016 and August, 2019.
 Methodology: A laboratory scale study was carried on three toxicants using dehydrogenase inhibition test. The inhibition of dehydrogenase activity of the isolate by toxicant was calculated relative to the control. All the dose-response relationships of the individual toxicants and that of themixtures were described by logistic dose model and Weibullcum model parameter.
 Results: The results revealed that the median inhibitory concentrations (IC50) observed were 1,067.33 ± 36.68 mg/L for drysate; 2,180.00 ± 147.31 mg/L for weedcut and 4,550.00 ± 62.45 mg/L for aminoforce. Duncan tests indicated that the IC50 of the toxicants were significantly different from each other. Among the individual toxicants, the ascending toxicities ranking were aminoforce > weedcut > drysate. The responses of the test organism to the stresses of the toxicants were dose-dependent and the toxicants also progressively repressed the dehydrogenase activity as the concentration increased. All binary mixtures were strongly synergistic against the organism.
 Conclusion: Thus, the toxicity of individual compound and synergistic effects of the mixtures of the toxicants indicates potential deleterious effects of both the individual chemicals and their mixtures to the rhizobacteria of Oryza sativa plant.

Toxicity of Quaternary Mixture of Formulated Glyphosate and Phenols on Providencia vermicola Dehydrogenase Activity

Aims: To assess the toxicity of glyphosate (as an active ingredient in drysate), three phenols (2,4-dichlorophenol, 4-chlorophenols and phenol) and quaternary mixtures of glyphosate, 2,4-dichlorophenol, 4-chlorophenol and phenol on the dehydrogenase activity (DHA) of P. vermicola.
 Study Design: The glyphosate, 2,4-dichlorophenol, 4-chlorophenol and phenol mixture ratios (%) were designed as: 25%:25%:25%:25%; 30%:20%:20%:30%, 40%:10%:10%: 40%; 50%:5%:30%:15% and 20%:20%:10%:50% for the respective mixtures in the concentration range of 0-1000 mg/L.
 Place and Duration of Study: Silver Press Laboratory, Owerri Nigeria between July, 2016 and August, 2019.
 Methodology:A laboratory scale study was carried on four toxicants using dehydrogenase inhibition test. The inhibition of dehydrogenase activity of the isolate by toxicant was calculated relative to the control. The percentage inhibition data generated was fitted into a logistic dose response model and Weibulleum to obtain their respective IC50.
 Results:The results revealed that the median inhibitory concentrations (IC50) of the mixtures on the Providencia vermicola were 247.17 ±10.20, 163.44 ± 8.18, 251.33 ± 45.25, 267.30 ± 8.76 and 178.93 ± 45.53 mg/L, respectively. Toxicity index (TI) model was used to evaluate the joint action toxicity of the mixtures on the test organism and was 60 % antagonistic.
 Conclusion: Thus, these synergistic and additive interactions of formulated glyphosate with the intermediates of 2,4-D was possible against the dehydrogenase activity of Providenciavermicola an important plant growth promoting bacterium. The dynamics of the toxic effects thus would depend on the concentration of the compounds.

Inhibitory Potentials of Hunteria umbellata Seed Extracts on Some Key Enzymes of Diabetes Mellitus with Profiling of its Phenolic Constituents

Background: The seeds of Hunteria umbellatais a common folkloric plant used in the management of Diabetes mellitus in Nigeria. Though there are many reports on its antidiabetic potential, there is a scarcity of information on its mechanisms of antidiabetic action. This study was designed to investigate the mechanism of antidiabetic action of H. umbellata seed by evaluating the inhibitory effect of its extracts on enzymes that are targeted in the management of diabetes mellitus. Methods: Dried seeds of H. umbellata were powdered and extracted separately in water and ethanol. Alpha-amylase, α-glucosidase, and sorbitol dehydrogenase inhibitory activities of the concentrated extracts were determined spectrophotometrically. Furthermore, the phenolic profile of the seed was determined using HPLC-UV analysis. Results: The inhibitory effect of both ethanol and aqueous extracts H. umbellataon the selected enzymes were similar with IC50 value of 40.36 ± 2.92 and 40.25 ± 4.53 mg/mL for α-amylase, 45.42 ±2.44 and 39.32 ± 3.46 mg/mL for α-glucosidase, and 36.25 ± 2.31 and 32.35 ± 1.53 mg/mL for sorbitol dehydrogenase, respectively. Kinetic studies showed that α-amylase was inhibited competitively, while both α-glucosidase and sorbitol dehydrogenase were inhibited in a non-competitive manner. The phenolic compounds identified in the H. umbellata seed were gallic acid, catechin, p-coumaric acid, rutin, and ferulic acid. Conclusion: The H. umbellata seed extract’s antidiabetic action may be by inhibiting the activities of α-amylase, α-glucosidase, and sorbitol dehydrogenase. This inhibition could be due to the presence of phytochemicals such as phenolic compounds in the plant.

Petroleum Contaminated Seawater Detoxification in Microcosm by Halotolerant Consortium Isolated from Persian Gulf.

Bioremediation of a petroleum contaminated seawater from Persian Gulf was investigated and efficiency of natural attenuation by native halotolerant bacterial consortium, biostimulation by addition of macro nutrients (nitrogen and phosphorus) and surfactant and bioaugmentation by application of halotolerant hydrocarbon degrading strains were evaluated. Biodegradation rates in defined conditions were studied for 30 days. Four pure isolates including Bacillus sp. PG-1, Pseudomonas aeruginosa PG-2, Paenibacillus lautus PG-3, and Pseudomonas putida PG-4 were used to preparation of bacterial consortium. Results indicated that the bioaugmentation yielded the best TPH removal efficiency of 56.24%, followed by biostimulation with surfactant addition (removal of 31.52%). The most bacterial density was also observed for bioaugmentation bioreactor. Toxicity of reaction medium was evaluated by oxygen consumption rate inhibition, dehydrogenase activity inhibition and growth rate inhibition methods in which, the least toxicity rates of 27%, 25% and 31% were observed for bioaugmentation based bioreactor, respectively. Simultaneous bioaugmentation and biostimulation can efficiently reduce the crude oil content in the surface of seawater using halotolerant strains.

Predicting the Toxicities of Ternary Mixtures of two Metals and Sodium Dodecyl Sulfate to Serratia marcescens (SerEW01) from Otamiri River Water

Background: Otamiri river server as a source of water for domestic activities, urban farming, recreation, aquatic foods in Owerri and environs. It also receives untreated domestic, industrial and agricultural waste water and run offs from the municipality. Seepages from solid wastes dumps at the river banks and sand mining activity going on in the river could also constitute environmental hazards
 Aims: This study aims at evaluating the interactive effects of the ternary mixtures of sodium dodecyl sulfate (SDS) and some divalent metals on preponderant bacterium (Serratia marcescens (SerEW01)) from the river.
 Study Design: Fixed ratio ray design was used for the study, with inhibition of dehydrogenase activity as end point.
 Place and Duration of Study: Owerri, Imo State, Nigeria, June – December, 2019.
 Methodology: The bacterium was earlier isolated as the preponderant bacterium isolate from the river water. Fixed ratio ternary mixtures (Equieffect concentration (EEC50) and arbitrary concentration (ABCR) ratios), SDS + Pb + Zn, SDS + Cd +Zn, SDS + Pb +Ni, SDS + Ni + Cd, SDS + Co + Pb and SDS + Co + Cd were designed to evaluate the combined toxicities of these toxicants. Toxicities predicted by concentration addition (CA) and independent action (IA) models were compared with the experimentally observed toxicities.
 Results: The EC50S observed ranged from 0.046 ± 0.003 mM (Zn) to 2.329 ± 0.092 mM (SDS). The EC50S of the toxicants were statistically different from each other (P<0.05). The order of increasing toxicities were SDS >Pb >Ni > Co > Cd(II) >Zn. Concentration-dependent toxicities with progressive inhibition of the dehydrogenase activity as the concentration increased were observed.. In all ternary mixtures, both the experimentally derived, CA and IA-predicted EC50S were statistically different from each other. Both models predicted lower toxicities compared to the experimental data. The Toxic Index and Model Deviation Ratio indicated synergistic interaction of SDS and metal ions against S. marcescens (SerEW01)
 Conclusion: This study could constitute base line information towards assessing the possible environmental hazards associated with co-contamination of the environment by SDS and divalent heavy metals, more so when both pollutants are common aquatic pollutants.

Potent human dihydroorotate dehydrogenase inhibitory activity of new quinoline-4-carboxylic acids derived from phenolic aldehydes: Synthesis, cytotoxicity, lipophilicity and molecular docking studies

A series of novel 2-substituted quinoline-4-carboxylic acids was synthesized by Doebner reaction starting from freely available protocatechuic aldehyde and vanillin precursors. Human dihydroorotate dehydrogenase (hDHODH) was recognised as a clear molecular target for these heterocycles. All compounds were also tested for their antiproliferative potential against three cancer cells (MCF-7, A549, A375) and one normal cell line (HaCaT) to evaluate the selective cytotoxicity. Quinoline derivatives 3f and 3g were identified as potent hDHODH inhibitors while 3k and 3l demonstrated high cytotoxic activity against MCF-7 and A375 cells and good selectivity. In addition, the logD7.4 values obtained by the experimental method were found to be in the range from −1.15 to 1.69. The chemical structures of all compounds were confirmed by IR, NMR and elemental analysis. The compounds pharmacology on the molecular level was revealed by means of molecular docking, highlighting the structural differences that distinguish highly active from medium and low active hDHODH inhibitors.

Inhibition of dehydrogenase activity in S. typhimurium by ethanolic and methanolic extracts of Carica papaya and Ocimum gratissimum

Dehydrogenase and inhibitions of dehydrogenase activities in Salmonella typhimurium by ethanolic and methanolic leaf extracts of Ocimum gratissimum and Carica papaya were investigated. Dehydrogenase activity assay was carried out using 2, 3, 5-triphenyl tetrazolium chloride (TTC) as the electron acceptor. Pure culture of S. typhimurium was exposed to varied concentrations of ethanolic and methanolic extracts of Ocimum gratissimum and Carica papaya [0-4000 μg/ml]. The ethanolic and methanolic extracts exhibited a concentration dependent response against the tested organism. Results obtained revealed that the ethanolic extracts showed a higher bactericidal effect on the test organism than the methanolic extracts at the threshold and total inhibitory concentrations. The IC50 were 45.349 and 15.697; IC100 were 43.732 and 35.526 for ethanolic extracts of Carica papaya and Ocimum gratissimum respectively while the IC50 were 7.108 and 13.696; IC100 were 40.815 and 31.104 for methanolic extracts of Carica papaya and Ocimum gratissimum respectively. This in-vitro study further revealed that the leaf of Carica papaya was more potent on Salmonella typhimurium than the leaf of Ocimum gratissimum. The findings from this study seem to provide the in-vitro evidence that justifies Carica papaya and Ocimum gratissimum as good candidate medicinal plants for the potential treatment of Salmonella typhimurium infections.

Integrated Treatment of Saline Oily Wastewater Using Sono-Electrokinetic Process, Degradation Mechanism, and Toxicity Assessment

Integration of sonication (US) with electrokinetic (EK) oxidation was studied for the treatment of a saline oily wastewater, as well as the effect of operating parameters, including pH, voltage, electrode distance (ED), sonication power, and reaction time on COD removal. A COD removal of 98 % was observed for the sono-electrokinetic (SEK) process with an applied voltage of 2.5 V, US power of 300 W, initial COD concentration of 3850 mg L–1, and reaction time of 9 h. The efficiency of SEK over sonication alone and EK oxidation alone was also confirmed with a higher pseudo-first-order reaction rate constant of 0.43 h–1, compared to values of 0.13 and 0.01 for alternative processes. In addition, the biodegradability of effluent was improved based on average oxidation state (AOS) and carbon oxidation state (COS) analysis. Oxygen consumption rate inhibition, dehydrogenase activity inhibition, and growth rate inhibition methods demonstrated the low toxicity of effluent (12–15 %) compared to influent. The current work indicated that SEK is a reliable and efficient technology for the treatment of saline oily wastewaters containing recalcitrant aromatic organics.

Toxicity of Binary Mixtures of Phenol, Zinc and Cadmium to Yeast Strains Isolated from Hydrocarbon Impacted Soil

Toxicity of zinc, cadmium and phenol and their binary mixtures were determined based on inhibition of dehydrogenase activities of yeasts strains isolated from hydrocarbon impacted soil. The yeasts isolated from the hydrocarbon impacted soil were identified as Saprochaete sp. and Cryptococcus sp. The toxicity of chemicals and their mixtures were evaluated in the concentration range of 0 - 16 mM for phenol, 0 - 5 mM for zinc and 0 - 0.4 mM for cadmium. The binary mixture ratios were evaluated. The toxicity thresholds (IC50) were estimated using 3-parameter logistic dose-response model. The IC50 shows that cadmium has the highest toxic effect on the yeasts with IC50 value of 0.075 mM for Saprochaete sp. and 0.09 mM for Cryptococcus sp. The binary toxicity of the mixtures on the enzyme activity of the yeasts was evaluated with toxic index (TI) model. Modulation of the toxic interactions by the components of the mixtures through synergistic, additive and antagonistic interactions on the heavy metals and phenol were possible against the dehydrogenase activity of the yeasts. However, the toxic effects of phenol and heavy metals would depend on their relative amount present in the environment.

Antibacterial effect of TiO2 :Cu:Ag thin coatings on Pseudomonas strain measured by microbiological and ATP assays.

The aim of this study is to investigate the antimicrobial properties of nanocomposite thin TiO2 :Cu:Ag films on Pseudomonas putida as a natural isolate and an opportunistic pathogen. Several different methods were used to compare the antibacterial effect of thin TiO2 :Cu:Ag layers obtained by radiofrequency magnetron sputter deposition against P. putida: optical density of the bacterial suspension, most probable number of survived cells, dehydrogenase activity inhibition, scanning electron microscopy images, atomic flame absorption spectroscopy, and adenosine triphosphate (ATP) luminescent assay. Optical density measurements and most probable plate count were in agreement and showed a strong bactericidal effect of the as-deposited and only bacteriostatic effect of the annealed coatings with the same metal content on tested bacteria. As the metal quantity in the medium rises during the first hour of the experiment, it could be suggested that this is the main reason for cell death. ATP-luminescent assay showed up to 18-fold reduction of the signal. It was compared with other microbiological and biochemical assays to prove the strong antibacterial effect of nanocomposite thin TiO2 :Cu:Ag coatings with the possibilities of medical applications. Protection of medical devices against infections is a significant current challenge raised by an increasing number of medical devices-associated infections and microbial resistance to conventional antibiotic and multidrug treatments. Deposition of antimicrobial coatings is one of the current approaches to mitigate the problem.

Response of soil microbes after direct contact with pyraclostrobin in fluvo-aquic soil

Agricultural chemicals affect the daily life of food production. However, the abuse of pesticides led to the damage to the environment. Pyraclostrobin (PYR) is commonly used strobilurin fungicide which inhibits fungal respiration through mitochondrial cytochrome-b and c1 inhibition. There is increasing concerns that PYR may adversely impact the environment. Although impacts on ecological receptors have been detailed, little information is available regarding the toxicological impact of PYR on soil microbial community dynamics and functioning. Understanding the potential impact on soil microbial populations is important. The activity of enzymes (urease, dehydrogenase, and β-glucosidase) and diversity of microbial community structure using high-throughput 16S rRNA sequencing were evaluated at different soil-PYR concentrations (0.1, 1.0, and 2.5 mg/kg) over a 48 day exposure period. Urease activity remained stable in general. Pyraclostrobin inhibited dehydrogenase activity during the exposure period. The β-glucosidase activity was inhibited on day 28 and induced on day 48 at 1.0 and 2.5 mg/kg. The genera Gp6, Exiguobacterium, Gp4, and Gemmatimonas were both the dominant genera and significantly changed genera. Pyraclostrobin had different level of influence on soil microbes containg their enzyme activity and community structure. The purpose of the current study was to examine the impact of PYR addition on soil enzymes as an indicator of soil health and to have complementary data on the impact of microbial populations. Furthermore, the study may also be the guide for further rational pesticide selection.

Comparison of four test methods for toxicity evaluation of typical toxicants in petrochemical wastewater on activated sludge

The shock impact of toxic pollutants in petrochemical wastewater on the activated sludge in biological treatment system is a key factor restricting the treatment efficiency. It is necessary to evaluate the toxicity of these pollutants by appropriate methods. In this study, four test methods were used to evaluate the toxicity of characteristic organic pollutants in petrochemical wastewater including 2,4-dichlorophenol, formaldehyde and pyridine, as well as one frequently-used reference toxicant 3,5-dichlorophenol. The sensitivity, accuracy and response time were compared among these methods: the oxygen consumption rate inhibition method (OCRIM), the dehydrogenase activity inhibition method (DAIM), the nitrification rate inhibition method (NRIM) and the growth rate inhibition method (GRIM). Principal component analysis was used to evaluate the correlation among the results of different methods. The OCRIM was comprehensively outstanding with the highest correlation between concentration and inhibition ratio (R2 values were all higher than 0.9854), good sensitivity, best accuracy (error value of the effective concentrations below 0.15 mg/l) and fastest response (<40 min). The sensitivity of the NRIM was found to be the highest in this study (10% effective inhibition concentration (EC10) value of 3,5-dichlorophenol was only 0.03 mg/l). Therefore, combined tests of OCRIM and NRIM were suggested.

IMB-SD62, a triazolothiadiazoles derivative with promising action against tuberculosis

One lead 3,6-disubstituted 1,2,4-triazolo[3,4-b][1,3,4]thiadiazole was identified as an inhibitor of shikimate dehydrogenase with antitubercular activity. Following up this compound, we optimized the lead through systematic modification of the 3 and 6 positions. The antitubercular activities in vitro, shikimate dehydrogenase inhibitory activities and cytotoxicity of derivatives were determined. We found IMB-SD62 with lower cytotoxicity and better activity. Thus, we studied the in vivo efficacy of IMB-SD62 against Mycobacterium tuberculosis and pharmacokinetics of IMB-SD62. In vivo acute M. tuberculosis H37Rv infection assay, IMB-SD62 showed antitubercular activity with the mean lung CFU counts decreasing 1.7 lg. The plasma pharmacokinetics study in rats showed that the oral bioavailability of IMB-SD62 was 14% and the half time was 1.05 h. The results of tissue distribution indicated that IMB-SD62 was mainly absorbed by liver and lung. In vitro metabolism study suggested that the metabolic ways of IMB-SD62 were dealkylated, oxidized and demethylated. CYP enzyme inhibition of IMB-SD62 in human liver microsomes was also evaluated. IMB-SD62 showed barely inhibition on CYP3A4 and CYP2D6. The excretion study manifested that IMB-SD62 was mainly eliminated by fecal excretion in rats. We concluded that based on these pharmaceutical properties, IMB-SD62 has the potential to be developed into new TB drug.