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Cells ◽  
2022 ◽  
Vol 11 (2) ◽  
pp. 195
Author(s):  
Quaiser Saquib ◽  
Abdullah M. Al-Salem ◽  
Maqsood A. Siddiqui ◽  
Sabiha M. Ansari ◽  
Xiaowei Zhang ◽  
...  

Tris(1,3-Dichloro-2-propyl)phosphate (TDCPP) is an organophosphorus flame retardant (OPFR) widely used in a variety of consumer products (plastics, furniture, paints, foams, and electronics). Scientific evidence has affirmed the toxicological effects of TDCPP in in vitro and in vivo test models; however, its genotoxicity and carcinogenic effects in human cells are still obscure. Herein, we present genotoxic and carcinogenic properties of TDCPP in human liver cells (HepG2). 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) and neutral red uptake (NRU) assays demonstrated survival reduction in HepG2 cells after 3 days of exposure at higher concentrations (100–400 μM) of TDCPP. Comet assay and flow cytometric cell cycle experiments showed DNA damage and apoptosis in HepG2 cells after 3 days of TDCPP exposure. TDCPP treatment incremented the intracellular reactive oxygen species (ROS), nitric oxide (NO), Ca2+ influx, and esterase level in exposed cells. HepG2 mitochondrial membrane potential (ΔΨm) significantly declined and cytoplasmic localization of P53, caspase 3, and caspase 9 increased after TDCPP exposure. qPCR array quantification of the human cancer pathway revealed the upregulation of 11 genes and downregulation of two genes in TDCPP-exposed HepG2 cells. Overall, this is the first study to explicitly validate the fact that TDCPP bears the genotoxic, hepatotoxic, and carcinogenic potential, which may jeopardize human health.


Author(s):  
Mônica Gomes ◽  
Eduardo Correia ◽  
Max Gomes ◽  
Claudio dos Santos ◽  
Caroline Barros ◽  
...  

The cariogenic processes are mainly caused by the bacterium Streptococcus mutans (S. mutans) and consist of the demineralization of the tooth that occurs when the acid production overcomes the natural repair or if a problem occurs in the last one. In this work, we performed the synthesis of twenty-one 1,4-naphthoquinones tethered to 1,2,3-1H-triazoles (8a-8k and 9a-9j), antibacterial evaluation against the S. mutans in vitro and the acute toxicity of the better ones in vivo. We observed strong inhibition results in the disc diffusion test ranging, the halos of inhibitions, from 18.66 (± 0.57) to 29 (± 2.64) mm, and good values in the minimum inhibitory concentration (5 to 50 μg), for the compounds 9e, 9h, 9i and 9j. Furthermore, they do not have a cytotoxic effect at the concentrations tested. Besides that, in the in vivo test, they show some slight alteration in the histopathological analyses and the biochemistry. Thus, we found four potential candidates to become instruments for the treatment of cavities.


2021 ◽  
Vol 37 ◽  
pp. e37089
Author(s):  
Mark Paul Selda Rivarez ◽  
Elizabeth P. Parac ◽  
Niño R. Laurel ◽  
Benjamin V. Cunanan ◽  
Angelie B. Magarro ◽  
...  

Anthracnose is a foliar and fruit disease caused by Colletotrichum spp. affecting a wide range of crops. Infection occurs early followed by quiescence in fruits, such as in banana, where chemical-based pesticides are used as a dependable fungal control for many years. There is an increasing need for a safe control and as implicated in the Organic Agriculture Act of 2010 (RA 10068) in the Philippines. This scenario drove the use of alternative pest control such as the use of biologicals and natural products. In this study, seven bacteria were isolated from wild honey, produced by Apis mellifera, wherein four (BC2, BC3, BC6 and BC7) were found to be an effective antagonist against Colletotrichum musae in in vitro conditions. These bacteria were identified to belong to the genus Lactobacillus spp. (BC2, BC3, BC7) and Bacillus spp. (BC6) based on sugar utilization tests, morphological and cultural growth in PDPA. For the in vivo test, different dilutions of wild honey were used and it was found out that lower concentrations were effective as biopesticide spray to prevent anthracnose infection. Lastly, we report herewith the first isolation of bacteria with biological control potential from wild honey, and to apply the raw or natural product as biopesticide in postharvest fruits.


2021 ◽  
Vol 30 (2) ◽  
pp. 141
Author(s):  
Anella Retna Kumala Sari ◽  
Arrohmatus Syafaqoh Li’aini

<p>Antraknosa yang disebabkan oleh Colletotrichum capsici masih menjadi penyakit utama yang menyerang buah cabai merah. Selama ini, penggunaan Curcuma aeruginosa sebagai antimikrobe patogen penyebab penyakit pada manusia lebih populer daripada sebagai antimikrobe fitopatogen. Rimpang Curcuma diketahui mengandung senyawa volatil/atsiri dan nonvolatil. Potensi senyawa volatil/atsiri Curcuma sebagai antimikrobe telah banyak dilaporkan, namun masih sangat terbatas untuk senyawa nonvolatilnya. Penelitian ini bertujuan mengetahui efektivitas antifungi senyawa nonvolatil dari ekstrak C. aeruginosa terhadap C. capsici pada buah cabai merah. Penelitian dilaksanakan pada bulan November 2014 hingga Mei 2015 di Universitas Brawijaya. Senyawa nonvolatil didapatkan dengan merendam rimpang C. aeruginosa menggunakan pelarut metanol kemudian didistilasi menggunakan rotary vacuum evaporator dan diidentifikasi menggunakan HPLC. Efektivitas antifungi senyawa nonvolatil dari ekstrak rimpang C. aeruginosa diuji secara in vitro dan in vivo di laboratorium menggunakan Rancangan Acak Lengkap dengan tiga kali ulangan. Perlakuan yang diujikan yaitu konsentrasi senyawa nonvolatil terdiri atas 0 (kontrol), 4, 6, 8, 10, dan 12 ppm. Senyawa nonvolatil dari ekstrak rimpang C. aeruginosa sangat efektif menghambat pertumbuhan C. capsici baik secara in vivo maupun in vitro di laboratorium bahkan konsentrasi 12 ppm menunjukkan persentase penghambatan antraknosa hingga 100%. Hasil identifikasi HPLC menunjukkan bahwa senyawa nonvolatil dari ekstrak rimpang C. aeruginosa mengandung kelompok Curcuminoid yang terdiri atas curcumin dan demethoxycurcumin yang berperan sebagai antifungi sehingga sangat berpotensi dikembangkan sebagai fungisida nabati.</p><p><strong>Keywords</strong></p><p>Antraknosa; Cabai merah; C. aeruginosa; Senyawa nonvolatil</p><p><strong>Abstract</strong></p><p>Anthracnose caused  by Colletotrichum capsici  is  still  as  major disease against  chilli pepper fruit. During this time, utilization of C. aeruginosa as pathogen antimicrobial caused disease to human is more popular than to crops. Curcuma has been known containing volatile and nonvolatile compound. Potential of volatil compound from Curcuma as antipathogen has been reported widely, nevertheless it is still limited known for nonvolatile compound. This research aimed to understand the antifungi effectivity of nonvolatile compound from C. aeruginosa extract to C. capsici on chilli pepper fruit. Research was conducted in November 2014 to Mei 2015. Nonvolatile compound was obtained by soaking C. aeruginosa rhizome into methanol solvent then distilated using rotary vacuum evaporator  and identified with HPLC instrument. Antifungi  effectivity  of nonvolatile compound  from  C. aeruginosa  extract  was experimented by in vitro and in vivo test using Completely Randomized Design with three replications. Treatments tested were various concentrations of nonvolatile compound namely 0 (control), 4, 6, 8,10, and 12 ppm. Nonvolatile compound from C. aeruginosa extract was highly effective to inhibit growth of C. capsici by both in vitro and in vivo test. HPLC identification result showed nonvolatile compound from C. aeruginosa extract contains Curcuminoid group play role as antifungi.</p>


2021 ◽  
Vol 25 (2) ◽  
pp. 147
Author(s):  
Lalu Muhammad Sakti Surya Jagat ◽  
Ida Bagus Gede Darmayasa ◽  
I Made Sara Wijana

Aspergillus flavus contamination of agriculture in Indonesia can cause problems to animal health and productivity. Some factors can support the appearance of contamination in feed, especially temperature and humidity. The main objective of this research was to investigate potency of Rhizopus spp. on inhibit A. flavus FNCC6109 in broiler chicken concentrate feed. The experiments were conducted dual culture method and the inhibition test of the Rhizopus spp. filtrate culture was incubated for 3, 4 and 5 days on in vitro. The in vivo test was directly applied in broiler chicken concentrate feed which added Rhizopus spp. filtrate culture concentration at 10% (v/v), 20% (v/v), 30% (v/v), 40% (v/v), dan 50% (v/v). The results showed that the Rhizopus spp. filtrate culture significantly (P?0,05) to inhibit the growth of A. flavus FNCC6109 both in vitro and in vivo. The percentage inhibition of Rhizopus spp. filtrate culture incubated for 5 days showed 67,47±2,10% relatively better results than 3 and 4 days, and therefore was used in the in vivo. Application of 50% (v/v) Rhizopus spp. filtrate culture to the broiler chicken concentrate feed significantly reduced 82% population of A. flavus FNCC6109 after 15 days incubated relative to that of negative control (concentrate feed without addition Rhizopus spp. filtrate culture and A. flavus FNCC6109).


2021 ◽  
Vol 22 (24) ◽  
pp. 13538
Author(s):  
Erina Shiraishi ◽  
Keishi Ishida ◽  
Daisuke Matsumaru ◽  
Akiko Ido ◽  
Youhei Hiromori ◽  
...  

Propolis is a resinous mixture produced by bees from their secretions and plant material, so its composition varies depending on its botanical origin. Propolis has several beneficial bioactivities, but its skin sensitization properties have long been suspected. Nevertheless, the skin sensitization potency of Brazilian green propolis (BGP) has not been scientifically evaluated. Here, we used scientifically reliable tests to evaluate it. In vitro antigenicity test based on the human cell line activation test (OECD TG 442E) was performed by measuring the expression of CD54 and CD86, which are indicators of the antigenicity of test substances, on THP-1 and DC2.4 cells. BGP did not affect the expression of either marker on THP-1 cells, but upregulated the expression of CD86 on DC2.4 cells, suggesting that BGP may be a skin sensitizer. Then, we performed local lymph node assay (LLNA, OECD TG 429) as a definitive in vivo test. LLNA showed that 1.70% BGP primed skin sensitization and is a “moderate sensitizer”. Our results indicate scientific proof of the validity of arbitrary concentrations (1–2%), which have been used empirically, and provide the first scientific information on the safe use of BGP.


Toxics ◽  
2021 ◽  
Vol 9 (12) ◽  
pp. 355
Author(s):  
Dong-Han Lee ◽  
Seo-Yoon Choi ◽  
Ki-Kyung Jung ◽  
Jun-Young Yang ◽  
Ja-young Jeong ◽  
...  

Polyethylene glycol (PEG) is a polymer used for surface modification of important substances in the modern pharmaceutical industry and biopharmaceutical fields. Despite the many benefits of PEGylation, there is also the possibility that the application and exposure of the substance may cause adverse effects in the body, such as an immune response. Therefore, we aimed to evaluate the sensitization responses that could be induced through the intercomparison of nanomaterials of the PEG-coated group with the original group. We selected gold/silver nanomaterials (NMs) for original group and PEGylated silver/gold NMs in this study. First, we measured the physicochemical properties of the four NMs, such as size and zeta potential under various conditions. Additionally, we performed the test of the NM’s sensitization potential using the KeratinoSens™ assay for in vitro test method and the LLNA: 5-bromo-2-deoxyuridine (BrdU)-FCM for in vivo test method. The results showed that PEGylated-NMs did not lead to skin sensitization according to OECD TG 442 (alternative test for skin sensitization). In addition, gold nanomaterial showed that cytotoxicity of PEGylated-AuNMs was lower than AuNMs. These results suggest the possibility that PEG coating does not induce an immune response in the skin tissue and can lower the cytotoxicity of nanomaterials.


2021 ◽  
Vol 14 (12) ◽  
pp. 1255
Author(s):  
Ju-Hyun Lee ◽  
Chulhun Park ◽  
Kwon-Yeon Weon ◽  
Chin-Yang Kang ◽  
Beom-Jin Lee ◽  
...  

Itraconazole (ITZ) is a class II drug according to the biopharmaceutical classification system. Its solubility is pH 3-dependent, and it is poorly water-soluble. Its pKa is 3.7, which makes it a weak base drug. The aim of this study was to prepare solid dispersion (SD) pellets to enhance the release of ITZ into the gastrointestinal environment using hot-melt extrusion (HME) technology and a pelletizer. The pellets were then filled into capsules and evaluated in vitro and in vivo. The ITZ changed from a crystalline state to an amorphous state during the HME process, as determined using DSC and PXRD. In addition, its release into the gastrointestinal tract was enhanced, as was the level of ITZ recrystallization, which was lower than the marketed drug (Sporanox®), as assessed using an in vitro method. In the in vivo study that was carried out in rats, the AUC0–48h of the commercial formulation, Sporanox®, was 1073.9 ± 314.7 ng·h·mL−1, and the bioavailability of the SD pellet (2969.7 ± 720.6 ng·h·mL−1) was three-fold higher than that of Sporanox® (*** p < 0.001). The results of the in vivo test in beagle dogs revealed that the AUC0–24h of the SD-1 pellet (which was designed to enhance drug release into gastric fluids) was 3.37 ± 3.28 μg·h·mL−1 and that of the SD-2 pellet (which was designed to enhance drug release in intestinal fluids) was 7.50 ± 4.50 μg·h·mL−1. The AUC of the SD-2 pellet was 2.2 times higher than that of the SD-1 pellet. Based on pharmacokinetic data, ITZ would exist in a supersaturated state in the area of drug absorption. These results indicated that the absorption area is critical for improving the bioavailability of ITZ. Consequently, the bioavailability of ITZ could be improved by inhibiting precipitation in the absorption area.


Author(s):  
Sanadra Adeeb ◽  
Saja Adeeb ◽  
G. Chladek ◽  
W. Pakieła ◽  
A. Mertas

Purpose: The aim of the presented work was to investigate the impact of the S-P introduction into resin-based composites on their effectiveness against Enterococcus faecalis (E. faecalis). Design/methodology/approach: Seven experimental composites based on typical matrix were developed. Six of them contained a filler with antimicrobial properties (silver sodium hydrogen zirconium phosphate, S-P), while the control material contained only common reinforcement fillers. The materials were characterized in terms of the dispersion of the extender in the matrix and then subjected to microbiological tests. The efficiency in the reduction of E. faecalis in the microenvironment was tested. Findings: The composites show a satisfactory distribution of fillers and a high initial reduction of bacteria colonies for the tested strain of E. faecalis. The reduction in bacteria colonies achieved for S-P concentrations from 7% to 13% was similar (median value from 99.8 to 99.9%, when for control material and compound with 1% S-P the number of colonies increased compared to positive control. Research limitations/implications: Laboratory test results may differ from in vivo test performance. In addition, there are many models for conducting laboratory antimicrobial efficacy studies, the results of which are also varied. The cytotoxic tests, long-term investigations and in vivo experiments need to be performed in future experiments. Practical implications: E. faecalis is a Gram-positive bacterium that is commonly detected in persistent endodontic infections and may enter the root canal through the coronal part. Development of composites with antimicrobial properties against this bacterium is as important as obtaining efficacy against cariogenic bacteria. Originality/value: The antimicrobial effectiveness against E. faecalis of experimental composites with submicrometer-sized particles of S-P was not investigated until now.


2021 ◽  
Vol 12 ◽  
pp. 1297-1325
Author(s):  
Richard Liam Marchese Robinson ◽  
Haralambos Sarimveis ◽  
Philip Doganis ◽  
Xiaodong Jia ◽  
Marianna Kotzabasaki ◽  
...  

Manufacturers of nanomaterial-enabled products need models of endpoints that are relevant to human safety to support the “safe by design” paradigm and avoid late-stage attrition. Increasingly, embryonic zebrafish (Danio Rerio) are recognised as a key human safety relevant in vivo test system. Hence, machine learning models were developed for identifying metal oxide nanomaterials causing lethality to embryonic zebrafish up to 24 hours post-fertilisation, or excess lethality in the period of 24–120 hours post-fertilisation, at concentrations of 250 ppm or less. Models were developed using data from the Nanomaterial Biological-Interactions Knowledgebase for a dataset of 44 diverse, coated and uncoated metal or, in one case, metalloid oxide nanomaterials. Different modelling approaches were evaluated using nested cross-validation on this dataset. Models were initially developed for both lethality endpoints using multiple descriptors representing the composition of the core, shell and surface functional groups, as well as particle characteristics. However, interestingly, the 24 hours post-fertilisation data were found to be harder to predict, which could reflect different exposure routes. Hence, subsequent analysis focused on the prediction of excess lethality at 120 hours-post fertilisation. The use of two data augmentation approaches, applied for the first time in nano-QSAR research, was explored, yet both failed to boost predictive performance. Interestingly, it was found that comparable results to those originally obtained using multiple descriptors could be obtained using a model based upon a single, simple descriptor: the Pauling electronegativity of the metal atom. Since it is widely recognised that a variety of intrinsic and extrinsic nanomaterial characteristics contribute to their toxicological effects, this is a surprising finding. This may partly reflect the need to investigate more sophisticated descriptors in future studies. Future studies are also required to examine how robust these modelling results are on truly external data, which were not used to select the single descriptor model. This will require further laboratory work to generate comparable data to those studied herein.


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