Evaluation of Neuroprotective Effect of Gut Microbe in Parkinson's Disease: An In Silico and In Vivo Approach.

Parkinson's disease is a progressive neurodegenerative disorder marked by the death of dopaminergic neurons in the substantia nigra region of the brain. Aggregation of alpha-synuclein (α-synuclein) is a contributing factor to Parkinson's disease pathogenesis. The objective of this study is to investigate the neuroprotective effects of gut microbes on α-synuclein aggregation using both in silico and in vivo approaches. We focussed on the interaction between α-synuclein and metabolites released by gut bacteria that protect from PD. We employed three probiotic microbe strains against α-synuclein protein: Lactobacillus casei, Escherichia coli, and Bacillus subtilis, with their chosen PDB IDs being Dihydrofolate reductase (3DFR), methionine synthetase (6BM5), and tryptophanyl-tRNA synthetase (3PRH), respectively. Using HEX Dock 6.0 software, we examined the interactions between these proteins. Among the various metabolites, methionine synthetase produced by E. coli showed potential interactions with α-synuclein. To further evaluate the neuroprotective benefits of E. coli, an in vivo investigation was performed using a rotenone-induced Parkinsonian mouse model. The motor function of the animals was assessed through behavioural tests, and oxidative stress and neurotransmitter levels were also examined. The results demonstrated that, compared to the rotenone-induced PD mouse model, the rate of neurodegeneration was considerably reduced in mice treated with E. coli. Additionally, histopathological studies provided evidence of the neuroprotective effects of E. coli. In conclusion, this study lays the groundwork for future research, suggesting that gut bacteria may serve as potential therapeutic agents in the development of medications to treat Parkinson's disease. fig. 1.

Development of Alpha-Synuclein protein model against therapeutic aspects of Parkinson's disease.

JOURNAL/ijpha/04.03/01363791-202456010-00007/figure1/v/2024-03-07T095025Z/r/image-tiff Parkinson's disease (PD) is the most common neurodegenerative disease caused by the steady depletion of dopamine in the striatum due to the loss of dopaminergic neurons. Most of the current therapeutics work on rebuilding the striatal dopamine level through oral administration of levodopa which stops the symptoms of PD. But there is a long-term motor complication with these dopamine precursors. Moreover, no preventive treatment is available for PD. Thus, before finding a therapeutic treatment for PD, it is necessary to first understand the basic cause of PD. Moreover, alpha-synuclein oligomerization can be the major factor in PD. From the UniProt database, protein information was extracted, and the model was designed by homology modeling technique and validated by the model validation server. Hence, the designed model has 96.5% most favored region and 0% disallowed region. Therefore, the model is stable based on RC plot parameters.

Skincare Products as Sources of Mutagenic Exposure to Infants: An Imperative Study Using a Battery of Microbial Bioassays.

Infant skin is highly absorptive and sensitive to exposure from external agents (microbes, toxicants, heat, cold, etc.). Many specialized infant skincare products are currently commercially available. Although the manufacturers claim that their products are mild enough to suit the infant skin, these products need to be studied for their safety. Using animal models to examine the safety of the ever-increasing number of skincare products is not economically or logistically feasible. To overcome this problem, we suggest using a battery of microbial bioassays as a robust system for monitoring the mutagenic potential of skincare products. We picked popular infant skincare products from the Indian market and assessed them by using a battery of three microbial mutagenicity bioassays. Most of them showed significant and reproducible mutagenic potential. Our study results raise concerns about regular use of infant products and emphasize the need to enforce strict regulations for the manufacturing and safety assessment of infant products.

Assessment of mutagenicity caused by popular baby foods and baby plastic-ware products: An imperative study using microbial bioassays and migration analysis.

Specialized products for infants have become every parent's first choice. Although these products claim to be safe and mild for infant use, yet there is a need to monitor them using different tools for mutagenicity detection to ensure further safety. In this study, a range of popular ready to eat and powdered baby foods, formula milk powders and attractive plasticware for infants were picked from the Indian market and tested for their mutagenicity using two microbial bioassays based on Salmonella typhimurium, viz., Ames bacterial reversion assay and fluctuation assay. Furthermore, chemical migration analysis was done on the most toxic baby food and baby plasticware samples as shown by the bioassays to detect possible leaching of Bisphenol a (BPA), lead and Di-2 ethyl hexyl phthalate (DEHP). It was surprising to find that the products made for the most risk-prone group in the society, i.e., infants have a significant potential to cause mutagenicity.

Mushroom as a product and their role in mycoremediation.

Mushroom has been used for consumption as product for a long time due to their flavor and richness in protein. Mushrooms are also known as mycoremediation tool because of their use in remediation of different types of pollutants. Mycoremediation relies on the efficient enzymes, produced by mushroom, for the degradation of various types of substrate and pollutants. Besides waste degradation, mushroom produced a vendible product for consumption. However, sometimes they absorb the pollutant in their mycelium (biosorption process) and cannot be consumed due to absorbed toxicants. This article reviews the achievement and current status of mycoremediation technology based on mushroom cultivation for the remediation of waste and also emphasizes on the importance of mushroom as product. This critical review is also focused on the safety aspects of mushroom cultivation on waste.

Acetamide hydrolyzing activity of Bacillus megaterium F-8 with bioremediation potential: optimization of production and reaction conditions.

Bacillus megaterium F-8 exhibited an intracellular acetamide hydrolyzing activity (AHA) when cultivated in modified nutrient broth with 3% tryptone, 1.5% yeast extract, and 0.5% sodium chloride, at pH 7.2, 45 °C for 24 h. Maximum AHA was recorded in the culture containing 0.1 M of sodium phosphate buffer, (pH 7.5) at 45 °C for 20 min with 0.2 % of acetonitrile and resting cells of B. megaterium F-8 equivalent to 0.2 ml culture broth. This activity was stable up to 55 °C and was completely inactivated at or above 60 °C. Maximum acyl transferase activity (ATA) was recorded in the reaction medium containing 0.1 M of potassium phosphate buffer, (pH 8.0) at 55 °C for 5 min with 0.85 mM of acetamide as acyl donor and hydroxylamine hydrochloride as acyl acceptor and resting cells of B. megaterium F-8 equivalent to 0.94 mg cells (dry weight basis). This activity was stable up to 60 °C and a rapid decline in enzyme activity was recorded above it. Under the optimized conditions, this organism hydrolyzed various nitriles and amides such as propionitrile, propionamide, caprolactam, acetamide, and acrylamide to corresponding acids. Acyl group transfer capability of this organism was used for the production of acetohydroxamic acid. ATA of B. megaterium F-8 showed broad substrate specificity such as for acetamide followed by propionamide, acrylamide, and lactamide. This amide hydrolyzing and amidotransferase activity of B. megaterium F-8 has potential applications in enzymatic synthesis of hydroxamic acids and bioremediation of nitriles and amides contaminated soil and water system.

Use of Salmonella/microsome reversion bioassay for monitoring industrial wastewater treatment plants in Rajasthan, India.

Salmonella/microsome reversion assay was used as a biological parameter for monitoring the toxicity of common effluent treatment plant (CETP), Mandia road industrial area, Pali catering to textile industrial areas in Pali, Rajasthan. The influent and effluent water of CETP, surface water (Bandi river) and underground water were tested using Ames bioassay. The results showed presence of mutagens in surface water of Bandi river and the underground water in Pali. Further, comparison of mutagenicity of CETP influent and effluent water revealed that the treatment method employed at this plant has failed to remove mutagenic substances present in Pali textile wastewater. The study also showed that Ames assay is an important tool in genotoxic studies because of its simplicity, sensitivity to genetic damage, speed, low cost of experimentation and small amount of sample required. Further Ames assay, as seen from the results of this study, can be used as a monitoring tool for not only CETPs but also for other water resources. The outcomes of the Ames assay demonstrated its performance as a sensitive, cost-effective and relatively rapid screening tool to assess the genotoxic potential of complex environmental samples.

Genotoxic effect of ciprofloxacin during photolytic decomposition monitored by the in vitro micronucleus test (MNvit) in HepG2 cells.

PURPOSE: Ciprofloxacin (CIP), a broad-spectrum, second-generation fluoroquinolone, has frequently been found in hospital wastewaters and effluents of sewage treatment plants. CIP is scarcely biodegradable, has toxic effects on microorganisms and is photosensitive. The aim of this study was to assess the genotoxic potential of CIP in human HepG2 liver cells during photolysis. METHODS: Photolysis of CIP was performed in aqueous solution by irradiation with an Hg lamp, and transformation products were monitored by HPLC-MS/MS and by the determination of dissolved organic carbon (DOC). The cytotoxicity and genotoxicity of CIP and of the irradiated samples were determined after 24 h of exposure using the WST-1 assay and the in vitro micronucleus (MN) test in HepG2 cells. RESULTS: The concentration of CIP decreased during photolysis, whereas the content of DOC remained unchanged. CIP and its transformation products were not cytotoxic towards HepG2 cells. A concentration-dependent increase of MN frequencies was observed for the parent compound CIP (lowest observed effect level, 1.2 µmol L(-1)). Furthermore, CIP and the irradiated samples were found to be genotoxic with a significant increase relative to the parent compound after 32 min (P < 0.05). A significant reduction of genotoxicity was found after 2 h of irradiation (P < 0.05). CONCLUSIONS: Photolytic decomposition of aqueous CIP leads to genotoxic transformation products. This proves that irradiated samples of CIP are able to exert heritable genotoxic effects on human liver cells in vitro. Therefore, photolysis as a technique for wastewater treatment needs to be evaluated in detail in further studies, not only for CIP but in general.

Handmade paper and cardboard industries: in health perspectives.

Generally, handmade paper industries are considered as eco-friendly industries. These industries are known to use vegetable dyes which are thought to be safe and non-toxic. However, cardboard industries are considered as pollution-causing industries. The present study focuses on the genotoxic assessment of handmade paper and cardboard industry's effluent by Ames test using Salmonella typhimurium TA 98 and TA 100 strains. On mutagenicity analysis, effluents of both industries were found to be mutagenic with either one strain of Salmonella typhimurium or with both. Besides this, no significant difference was observed in effluent of both small-scale and large-scale handmade paper industries. Moreover, mutagenic compounds reach the nearby water body i.e. Amani Shah Drainage through connecting drain. Discharging of untreated effluent not only deteriorates the water quality but also reaches the food chain when used for irrigating nearby fields. Workers of these industries may suffer various health hazards when they are exposed to mutagenic effluent without having any information about it. Hence, discharging of effluents should thus be restricted or the workers while handling mutagenic substances should at least take proper precautions.

Bioremediation of industrial waste through mushroom cultivation.

Handmade paper and cardboard industries are involved in processing of cellulosic and ligno-cellulosic substances for making paper by hand or simple machinery. In the present study solid sludge and effluent of both cardboard and handmade paper industries was collected for developing a mushroom cultivation technique to achieve zero waste discharges. Findings of present research work reveals that when 50% paper industries waste is used by mixing with 50% (w/w) wheat straw, significant increase (96.38%) in biological efficiency over control of wheat straw was observed. Further, cultivated basidiocarps showed normal morphology of stipe and pileus. Cross section of lamellae did not show any abnormality in the attachment of basidiospores, hymenal trama and basidium. No toxicity was found when fruiting bodies were tested chemically.

Mutagenicity assessment of textile dyes from Sanganer (Rajasthan).

Sanganer town, district Jaipur (Rajasthan, India) is famous worldwide for its hand block dyeing and textile printing industries. These industries use a variety of chemicals and dyes during processing and finishing of raw materials. Most of the textile dyes used by these industries have not been evaluated for their impact on health and the environment. The workers in these industries are exposed to such dyes with no control over the length and frequency of exposure. Further, untreated and sometimes even treated effluents from these industries are released into surface waters of Amani Shah drainage or through the drainage systems, seep into the ground water and adjoining water bodies. Since many textile dyes are known carcinogens and mutagens, a complete evaluation of the safety of these dyes in the human environment must include an evaluation of their genotoxicity or mutagenicity. A total of 12 textile dyes from Sanganer were tested for their mutagenicity, by Ames Salmonella reversion assay using strain TA 100 of Salmonella typhimurium. Only 1 dye, Red 12 B showed absence of mutagenic activity. The remaining 11 dyes were all positively mutagenic.

Mutagenicity evaluation of industrial sludge from common effluent treatment plant.

Sludge from common effluent treatment plant (CETP) receiving effluents from textile industries at Mandia Road, Pali, was analyzed to assess the level of mutagenicity. Mutagenicity assay using Salmonella typhimurium tester strains TA 98 and TA 100 gave positive results, thus suggesting presence of genotoxic contaminants in the samples investigated. Further, mutagenic activity of chemical sludge was found to be lesser than that of biological sludge. This result is very surprising and unexpected as it is indicating that some mutagenic compounds are either being formed or certain promutagenic compounds are being converted into stable mutagenic metabolites during the biological treatment of the wastewater effluents. There have been no previous reports giving similar or contrary results. Most of the previous studies have reported effects of single combined sludge.

Photocatalytic degradation of aniline at the interface of TiO2 suspensions containing carbonate ions.

The degradation of aniline has been investigated using aqueous TiO2 suspensions containing carbonate ions as photocatalyst. The addition of carbonate to Degussa P-25 increased the number of active adsorption sites at its surface. For the TiO2 suspensions containing carbonate ions the intensity of adsorption of aniline increased to 6.9 x 10(2) from 5.5 x 10(2) mol(-1) dm(3) in case of bare TiO2 suspensions. This in turn results in the increased interfacial interaction of the photogenerated charge carriers with the adsorbed aniline and thus enhancing the rate of its photodecomposition to 6.5 x 10(-6) mol dm(-3) s(-1) compared to 2.7 x 10(-6) mol dm(-3) s(-1) in the absence of Na(2)CO(3). The maximum efficiency of this photocatalyst has been obtained upon addition of 0.11 mol dm(-3) of Na(2)CO(3) at pH 10.8. The photocatalytic action is understood by the simultaneous interaction of intermediates, *OH and CO*-(3), and their reactivity with aniline. Azobenzene, p-benzoquinone, nitrobenzene, and NH(3) have been identified as the major products of the photooxidation of aniline. Both the reactant and products have been followed kinetically. The photodegradation follows Langmuir-Hinshelwood Model. The mechanism of the occurring reactions has been analyzed and discussed. In the presence of Na(2)CO(3), 3 x 10(-3) mol dm(-3) of aniline could be photodegraded completely in about 6 h while all organic intermediates decomposed completely within about 10 h.

Genotoxicity of vegetables irrigated by industrial wastewater.

Wastewater effluents from textile dyeing and printing industries of Sanganer are discharged directly, without any treatment, into Amani Shah Nallah drainage. The drainage water takes the dissolved toxicants to flora and fauna, including crops and seasonal vegetables, being grown in the land adjoining the Nallah drainage. Thus mutagenic potential of vegetables irrigated by the water of Amani Shah Nallah drainage was investigated in the present study. The vegetables irrigated by ground water from Sanganer have also been analyzed to determine possible adverse effects of these wastewater effluents on aqua duct.

Mutagenicity assessment of effluents from textile/dye industries of Sanganer, Jaipur (India): a case study.

Sanganer town, district Jaipur (Rajasthan, India), is famous worldwide for its dyeing and printing industries. There are about 400 industries involved in textile printing processes, which discharge effluents into nearby ponds and drains, without any treatment. These effluents contain highly toxic dyes, bleaching agents, salts, acids, and alkalis. Heavy metals like cadmium, copper, zinc, chromium, and iron are also found in the dye effluents. Textile workers are exposed to such waters with no control over the length and frequency of exposure. Further, as the untreated effluents are discharged into the environment they can cause severe contamination of surface and underground water. Environmental pollution caused by such textile effluents results in adverse effects on flora, fauna, and the general health of not only the textile workers, but also the residents of Sanganer town. Therefore, to assess the possible genotoxic health risk and environmental genotoxicity due to the textile industry effluents, this study was carried out using the Ames Salmonella/microsome mutagenicity assay. The results clearly indicate that the effluents and the surface water of Amani Shah drainage have high mutagenic activity. Further, the drainage water and the dry bed of the drainage (during summer months) are not fit for agricultural or other recreational purposes. A low level of mutagenicity in the underground water of Sanganer again emphasizes the grave pollution problem existing in the area. Multiple post hoc comparison tests (LSD, Tukey's) were used for comparison of sample site, dose, and length of exposure. Quadratic Model was found to adequately fit the observed data.