Dihydrothiazolo ring-fused 2-pyridone antimicrobial compounds treat Streptococcus pyogenes skin and soft tissue infection.

We have developed GmPcides from a peptidomimetic dihydrothiazolo ring-fused 2-pyridone scaffold that have antimicrobial activities against a broad-spectrum of Gram-positive pathogens. Here we examine the treatment efficacy of GmPcides using skin and soft tissue infection (SSTI) and biofilm formation models by Streptococcus pyogenes. Screening our compound library for minimal inhibitory (MIC) and minimal bactericidal (MBC) concentrations identified GmPcide PS757 as highly active against S. pyogenes. Treatment of S. pyogenes biofilm with PS757 revealed robust efficacy against all phases of biofilm formation by preventing initial biofilm development, ceasing biofilm maturation and eradicating mature biofilm. In a murine model of S. pyogenes SSTI, subcutaneous delivery of PS757 resulted in reduced levels of tissue damage, decreased bacterial burdens and accelerated rates of wound-healing, which were associated with down-regulation of key virulence factors, including M protein and the SpeB cysteine protease. These data demonstrate that GmPcides show considerable promise for treating S. pyogenes infections.

Advances and perspectives of nanomaterials for photocatalytic degradation of biological ethylene toward the postharvest improvement of agricultural products.

To date, intensive emphasis is required to develop advanced postharvest technologies to ensure food security, increase nutrition, and improve farmers toward cleaner production. How to effectively degrade the harmful gaseous ethylene (C2H4) biosynthesis, which distributes heavy losses of fresh-cut fruits and vegetables, has received considerable attention. Among various advanced techniques, photocatalytic degradation of biological C2H4 is proposed as the most promising method to solve this issue. In this context, the recent studies on the photodegradation of C2H4 have been critically summarized and highlighted. Many photocatalysts, including TiO2-based and non-TiO2-based (metal oxides (ZnO, WO3, Ga2O3), molybdates (ß-Ag2MoO4), phosphides (Ag3PO4), perovskite oxides (Bi2WO6)) nanomaterials, have been revealed with credible performance results. Also, varying reaction parameters to optimize the photocatalytic degradation efficacy in the literature are summarized. We also discussed the current status, challenges, and prospects for enhanced photodegradation of C2H4 in this study. The efficacy and economics of photodegradation have played an essential role in selecting a particular type of photocatalyst. Although many efforts have been made, significant improvements are still required for photocatalysis. In this work, we have also successfully suggested some strategies to further promote this concept for controlling and degrading plant-generated C2H4 in fruit and vegetable postharvest in a sustainable and economically feasible manner.

A Highly Substituted Ring-Fused 2-Pyridone Compound Targeting PrfA and the Efflux Regulator BrtA in Listeria monocytogenes.

Listeria monocytogenes is a facultative Gram-positive bacterium that causes listeriosis, a severe foodborne disease. We previously discovered that ring-fused 2-pyridone compounds can decrease virulence factor expression in Listeria by binding and inactivating the PrfA virulence activator. In this study, we tested PS900, a highly substituted 2-pyridone that was recently discovered to be bactericidal to other Gram-positive pathogenic bacteria, such as Staphylococcus aureus and Enterococcus faecalis. We show that PS900 can interact with PrfA and reduce the expression of virulence factors. Unlike previous ring-fused 2-pyridones shown to inactivate PrfA, PS900 had an additional antibacterial activity and was found to potentiate sensitivity toward cholic acid. Two PS900-tolerant mutants able to grow in the presence of PS900 carried mutations in the brtA gene, encoding the BrtA repressor. In wild-type (WT) bacteria, cholic acid binds and inactivates BrtA, thereby alleviating the expression of the multidrug transporter MdrT. Interestingly, we found that PS900 also binds to BrtA and that this interaction causes BrtA to dissociate from its binding site in front of the mdrT gene. In addition, we observed that PS900 potentiated the effect of different osmolytes. We suggest that the increased potency of cholic acid and osmolytes to kill bacteria in the presence of PS900 is due to the ability of the latter to inhibit general efflux, through a yet-unknown mechanism. Our data indicate that thiazolino 2-pyridones constitute an attractive scaffold when designing new types of antibacterial agents. IMPORTANCE Bacteria resistant to one or several antibiotics are a very large problem, threatening not only treatment of infections but also surgery and cancer treatments. Thus, new types of antibacterial drugs are desperately needed. In this work, we show that a new generation of substituted ring-fused 2-pyridones not only inhibit Listeria monocytogenes virulence gene expression, presumably by inactivating the PrfA virulence regulator, but also potentiate the bactericidal effects of cholic acid and different osmolytes. We identified a multidrug repressor as a second target of 2-pyridones. The repressor-2-pyridone interaction displaces the repressor from DNA, thus increasing the expression of a multidrug transporter. In addition, our data suggest that the new class of ring-fused 2-pyridones are efficient efflux inhibitors, possibly explaining why the simultaneous addition of 2-pyridones together with cholic acid or osmolytes is detrimental for the bacterium. This work proves conclusively that 2-pyridones constitute a promising scaffold to build on for future antibacterial drug design.

Biogenic green metal nano systems as efficient anti-cancer agents.

Metal/metal oxide nano systems (M-NSs) of tunable and manipulative properties are emerging suitable for cancer management via immunity development, early-stage diagnosis, nanotherapeutics, and targeted drug delivery systems. However, noticeable toxicity, off-targeted actions, lacking biocompatibility, and being expensive limit their acceptability. Moreover, involving high energy (top-down routes) and hazardous chemicals (bottom-up chemical routes) is altering human cycle. To manage such challenges, biomass (plants, microbes, animals) and green chemistry-based M-NSs due to scalability, affordability, are cellular, tissue, and organ acceptability are emerging as desired biogenic M-NSs for cancer management with enhanced features. The state-of-art and perspective of green metal/metal oxide nano systems (GM-NSs) as an efficient anti-cancer agent including, imaging, immunity building elements, site-specific drug delivery, and therapeutics developments are highlighted in this review critically. It is expected that this report will serve as guideline for design and develop high-performance GM-NSs for establishing them as next-generation anti-cancer agent capable to manage cancer in personalized manner.

Natural Products as Potential Therapeutic Agents for SARS-CoV-2: A Medicinal Chemistry Perspective.

Coronavirus is a single-stranded RNA virus discovered by virologist David Tyrrell in 1960. Till now seven human corona viruses have been identified including HCoV-229E, HCoVOC43, HCoV-NL63, HCoV-HKU1, SARS-CoV, MERS-CoV and SARS-CoV-2. In the present scenario, the SARS-CoV-2 outbreak causing SARS-CoV-2 pandemic, became the most serious public health emergency of the century worldwide. Natural products have long history and advantages for the drug discovery process. Almost 80% of drugs present in market are evolved from the natural resources. With the outbreak of SARS-CoV-2 pandemic, natural product chemists have made significant efforts for the identification of natural molecules which can be effective against the SARSCoV- 2. In current compilation we have discussed in vitro and in vivo anti-viral potential of natural product-based leads for the treatment of SARS-CoV-2. We have classified these leads in different classes of natural products such as alkaloids, terpenoids, flavonoids, polyphenols, quinones, cannabinoids, steroids, glucosinolates, diarylheptanoids, etc. and discussed the efficacy and mode of action of these natural molecules. The present review will surely opens new direction in future for the development of promising drug candidates, particularly from the natural origin against coronaviruses and other viral diseases.

Polymer Membranes of Zeolitic Imidazole Framework-8 with Sodium Alginate Synthesized from ZIF-8 and Their Application in Light Gas Separation.

The potential of nanocomposite membranes (NCMs) prepared by the sodium alginate polymer and embedded with synthesized zeolitic imidazole framework-8 (ZIF-8) as fillers having microporous structure in the application of separation of gaseous mixture generated by the process of methane reforming was assessed. ZIF-8 crystals were created through hydrothermal synthesis, with sizes varying from 50 to 70 nm. NCMs were prepared with a 15% filler loading, i.e., synthesized ZIF-8. NCMs (ZIF-8) having H2 permeability of 28 Barrer and H2/CH4 selectivity of 125 outperformed neat polymer membranes in terms of separation performance at ambient temperature and 4 kg/cm2 pressure. The purity of H2 increased to as high as 95% among the measured values. The NCMs did not, however, outperform a neat polymer membrane in terms of their ability to separate mixtures of gases. Moreover, the combination of ZIF-8 as a filler with sodium alginate was new and had not been reported previously. As a result, it is worthwhile to investigate.

Prevalence and implications of microplastics in potable water system: An update.

Synthetic plastics, which are lightweight, durable, elastic, mouldable, cheap, and hydrophobic, were originally invented for human convenience. However, their non-biodegradability and continuous accumulation at an alarming rate as well as subsequent conversion into micro/nano plastic scale structures via mechanical and physio-chemical degradation pose significant threats to living beings, organisms, and the environment. Various minuscule forms of plastics detected in water, soil, and air are making their passage into living cells. High temperature and ambient humidity increase the degradation potential of plastic polymers photo-catalytically under sunlight or UV-B radiations. Microplastics (MPs) of polyethylene terephthalate, polyethylene, polystyrene, polypropylene, and polyvinyl chloride have been detected in bottled water. These microplastics are entering into the food chain cycle, causing serious harm to all living organisms. MPs entering into the food chain are usually inert in nature, possessing different sizes and shapes. Once they enter a cell or tissue, it causes mechanical damage, induces inflammation, disturbs metabolism, and even lead to necrosis. Various generation routes, types, impacts, identification, and treatment of microplastics entering the water bodies and getting associated with various pollutants are discussed in this review. It emphasizes potential detection techniques like pyrolysis, gas chromatography-mass spectrometry (GC-MS), micro-Raman spectroscopy, and fourier transform infrared spectroscopy (FT IR) spectroscopy for microplastics from water samples.

Prevalence of multidrug-resistant strains in device associated nosocomial infection and their in vitro killing by nanocomposites.

Background: As per WHO, global burden of healthcare-associated infections (HAIs) ranges between 7% and 12%. There is a dire need to screen Device associated nosocomial infections (DANIs) in hospitals(1). To investigate the prevalence of microbes in hospitals in DANI cases and analyse in vitro control of multi-drug resistant strains by nanotechnology intervention. Methods: Patients diagnosed with DANI were enrolled and monitored. Identification and antibiotic susceptibility pattern of the etiological agent of DANIs were made by the phenotypic method and Vitek 2 automated systems according to standard protocol. In addition, biosynthesized nanocomposite was analysed for their antimicrobial activity by agar well-diffusion method, CFU count and DNA degradation analysis. Results: There were a total of 324 patients diagnosed with DANIs. Total 369 microbial pathogens were isolated from DANI patients. The majority (87%) of the pathogenic microbes were gram-negative bacilli and all were multidrug-resistant. 41.5% of the gram-negative isolates were ESBL producers. Methicillin-resistant Staphylococcus aureus contributes about 7.3% of the total isolates in gram-positive bacteria. Nanocomposite showed 100% bactericidal activity at 5 mg/ml concentration within 3 h of incubation, whereas 2.5 mg/ml concentration of nanocomposites takes 6 h to inhibit complete growth. Conclusions: DANI, which was found in patients of all age groups, us due to multidrug-resistant gram-negative bacteria. The most commn causative agents were Acinetobacter baumannii and Citrobacter species. Nanocomposites can provide an alternative solution to prevent the DANIs.

Polypyrrole-based nanomaterials: A novel strategy for reducing toxic chemicals and others related to environmental sustainability applications.

Aqueous contaminants such as pharmaceuticals, dyes, personal care products, etc., are the common water contaminants that show adverse health effects. Photocatalysis is one of the well-known techniques to treat these water contaminants. Currently, most inorganic photocatalysts show a poor balance between adsorption and photocatalytic activity. In addition, heavy metal pollution and low biosafety are significant concerns in photocatalysis. Thus, environmentally friendly photocatalysts are required to avoid the secondary pollution caused by some inorganic semiconductor-photocatalysts. Organic polymer-based photocatalysts are low-cost, stable, non-toxic, and can utilize visible and NIR light for photocatalysis. In this review, we have discussed polypyrrole as a photocatalyst. Polypyrrole is a conducting organic polymer photocatalyst that is highly stable with high charge mobility and strong binding sites for photocatalytic reactions. Besides these advantages, polypyrrole has limitations, such as high charge recombination due to a small bandgap and poor dispersity. So we have explored the modifications to polypyrrole photocatalysts, such as doping and heterojunctions. Further, we have explained the applications of polypyrrole in photocatalysis as an adsorbent, sensitizer, degradation of pollutants, and energy production. Finally, the future aspects of polypyrrole photocatalysis are also explored to improve the path of future research.

Environmental impact of COVID-19 Vaccine waste: A perspective on potential role of natural and biodegradable materials.

The mass immunization is the prioritised post-pandemic phase offering preventive countermeasure for COVID-19 pandemic. However, it is crucial to tackle the environmental impact of COVID-19 vaccine waste for sustainable vaccination management because a prolonged immunisation campaign is expected. As the pace of vaccine production, distribution and mass vaccination has been expedited, there is a simultaneous rise in plastic derived vaccine waste including syringes, needles, used/unused vaccine vials, vaccine packaging, and protective gear (surgical facemasks, gloves, face shields, etc). Henceforth, in view of the repercussions of heaping plastic waste in the environment, this article provides a perspective on the usage of synthetic and natural materials as potential substituents for vaccination tools. The biodegradable polymeric gums such as cellulose, gellan, pectin, etc. have been successfully applied for the fabrication of surgical facemasks. The highly suggestive practice is replacement of conventional polypropylene based plastics with bioplastics or paper for vaccine packaging. The usage of biodegradable bio-plastics as packaging material along with environmentally friendly face masks can help to achieve the zero waste approach. The discussion in the article significantly highlights the necessity of opting sustainable solutions of disinfecting and substituting vaccination tools for an environment friendly ongoing vaccination campaign.

A review on bioactive phytochemicals and ethnopharmacological potential of purslane (Portulaca oleracea L.).

The Portulaca oleracea L. commonly known as purslane is distributed all over the world and easily grows in diverse soil and climatic conditions. It has been traditionally used as a nutritious and ethnomedicinal food across the globe. Various studies have shown that the plant is a rich source of various important phytochemicals such as flavonoids, alkaloids, terpenoids, proteins, carbohydrates, and vitamins such as A, C, E, and B, carotenoids and minerals such as phosphorus, calcium, magnesium and zinc. It is particularly very important because of the presence of a very high concentration of omega-3- fatty acids especially α-linolenic acid, gamma-linolenic acid and linoleic acid, which are not generally synthesized in terrestrial plants. Various parts of purslane are known for ethnomedicinal and pharmacological uses because of its anti-inflammatory, antidiabetic, skeletal muscle relaxant, antitumor, hepatoprotective, anticancer, antioxidant, anti-insomnia, analgesic, gastroprotective, neuroprotective, wound healing and antiseptic activities. Due to multiple benefits of purslane, it has become an important wonder crop and various scientists across the globe have shown much interest in it as a healthy food for the future. In this review, we provide an update on the phytochemical and nutritional composition of purslane, its usage as nutritional and an ethnomedicinal plant across the world. We further provide a detailed account on ethnopharmacological studies that have proved the ethnomedicinal properties of purslane.

Adjuvanted trivalent influenza vaccine versus quadrivalent inactivated influenza vaccine in Hutterite Children: A randomized clinical trial.

BACKGROUND: Children play an important role in the transmission of influenza. The best choice of vaccine to achieve both direct and indirect protection is uncertain. The objective of the study was to test whether vaccinating children with MF59 adjuvanted trivalent influenza vaccine (aTIV) can reduce influenza in children and their extended households compared to inactivated quadrivalent vaccine (QIV). METHODS: We conducted a cluster randomized trial in 42 Hutterite colonies in Alberta and Saskatchewan. Colonies were randomized such that children were assigned in a blinded manner to receive aTIV (0.25 ml of pediatric aTIV for ages 6 months to < 36 months or 0.5 ml for ages ≥ 36 months to 6 years) or 0.5 ml of QIV. Participants included 424 children aged 6 months to 6 years who received the study vaccine and 1246 family cluster members who did not receive the study vaccine. The primary outcome was confirmed influenza A and B infection using a real-time reverse transcriptase polymerase chain reaction (RT-PCR) assay. An intent to treat analysis was used. Data were collected from January 2017 to June 2019. RESULTS: The mean percentage of children who received study vaccine was 62% for aTIV colonies and 74% for QIV colonies. There were 66 (3.4%) with RT-PCR confirmed influenza A and B in the aTIV colonies (children and family clusters) versus 93 (4.4%) in the QIV colonies, hazard ratio (HR) 0.78 (95 %CI 0.36-1.71). Of these, 48 (2.5%) in the aTIV colonies and 76 (3.6%) in the QIV colonies had influenza A, HR 0.69, (95 %CI 0.29-1.66) while 18 (0.9%) and 17 (0.8%) in the aTIV versus QIV colonies respectively had influenza B, HR 1.22, (95 %CI 0.20-7.41). In children who received study vaccine, there were 5 Influenza A infections in the aTIV colonies (1.1%) compared to 30 (5.8%) in the QIV colonies, relative efficacy of 80%, HR 0.20, (95 %CI 0.06-0.66). Adverse events were significantly more common among children who received aTIV. No serious vaccine adverse events were reported. CONCLUSION: Vaccinating children with aTIV compared to QIV resulted in similar community RT-PCR confirmed influenza illness and led to significant protection against influenza A in children.

Combined amino acid PET-MRI for identifying recurrence in post-treatment gliomas: together we grow.

PURPOSE: The aim of this study is to compare the diagnostic accuracy of amino acid PET, MR perfusion and diffusion as stand-alone modalities and in combination in identifying recurrence in post-treatment gliomas and to qualitatively assess spatial concordance between the three modalities using simultaneous PET-MR acquisition. METHODS: A retrospective review of 48 cases of post-treatment gliomas who underwent simultaneous PET-MRI using C11 methionine as radiotracer was performed. MR perfusion and diffusion sequences were acquired during the PET study. The following parameters were obtained: TBRmax, TBRmean, SUVmax, and SUVmean from the PET images; rCBV from perfusion; and ADCmean and ADCratio from the diffusion images. The final diagnosis was based on clinical/imaging follow-up and histopathology when available. ROC curve analysis in combination with logistic regression analysis was used to compare the diagnostic performance. Spatial concordance between modalities was graded as 0, 1, and 2 representing discordance, < 50% and > 50% concordance respectively. RESULTS: There were 35 cases of recurrence and 13 cases of post-treatment changes without recurrence. The highest area under curve (AUC) was obtained for TBRmax followed by rCBV and ADCratio. The AUC increased significantly with a combination of rCBV and TBRmax. Amino acid PET showed the highest diagnostic accuracy and maximum agreement with the final diagnosis. There was discordance between ADC and PET in 22.9%, between rCBV and PET in 16.7% and between PET and contrast enhancement in 14.6% cases. CONCLUSION: Amino acid PET had the highest diagnostic accuracy in identifying recurrence in post-treatment gliomas. Combination of PET with MRI further increased the AUC thus improving the diagnostic performance.

Sustainable and green trends in using plant extracts for the synthesis of biogenic metal nanoparticles toward environmental and pharmaceutical advances: A review.

Conventionally utilized physical and chemical routes for constructing nanoparticles are not eco-friendly. They are associated with many shortcomings like the requirement of specially designed equipment, templates, extremely high temperature, and pressure. Biosynthesis seems to be drawn unequivocal attention owing to its upsurge of applications in different fields like; energy, nutrition, pharmaceutical, and medicinal sciences. To harness the biological sources, the present review describes an environment-friendly route to generate biogenic nanoparticles from the natural plant extracts and the followed mechanisms for their synthesis, growth, and stabilization. The present review summarizes the recent trends involved in the photosynthesis of metallic nanoparticles and their effective use in controlling malaria, hepatitis, cancer, like various endemic diseases. Also, various characterization approaches, such as UV-visible spectrophotometry, Fourier transform infrared spectroscopy, powder X-ray diffraction, scanning electron microscopy, transmission electron microscopy, and energy-dispersive X-ray spectroscopy, are discussed here examine the properties of as-fabricated nanoparticles. Various plant parts like leaves, stems, barks, fruit, and flowers are rich in flavonoids, phenols, steroids, terpenoids, enzymes, and alkaloids, thereby playing an essential role in reducing metal ions that generate metallic nanoparticles. Herein, the uniqueness of phytofabricated nanoparticles along with their distinctive antibacterial, antioxidant, cytotoxic, and drug delivery properties are featured. Lastly, this work highlights the various challenges and future perspectives to further synthesize biogenic metal nanoparticles toward environmental and pharmaceutical advances in the coming years.

Degradations of endocrine-disrupting chemicals and pharmaceutical compounds in wastewater with carbon-based nanomaterials: a critical review.

Although water occupies 75% of the earth's surface, only 0.0067% of the total water is available for human activities. These statistics further decline with the population growth and consequent multiplication in the amount of annual waste produced. The demand for clean and safe drinking water has always been a prime concern in the global scenario. Among various types of waste materials, endocrine-disrupting chemicals (EDCs) and pharmaceutical effluents have become a constant threat to the aquatic ecosystem and possess challenges worldwide. Endocrine-disrupting chemicals (EDCs) are a mixed group of emerging concern chemicals with the ability to mimic the mechanisms of biosynthesis, transport, and metabolism of hormones. These chemicals pose various health threats such as early puberty, infertility, obesity, diabetes, reproductive disorders, cancerous tumors, and related disorders (immune cells, hormones' activity, and various organs). On the other hand, pharmaceutical compounds such as antibiotics also harm the natural environment, human health, and soil microbiology. Their low concentration, ranging from a few ng/L to µg/L, gives rise to a micro-pollution phenomenon, which makes it difficult to detect, analyze, and degrade in wastewater treatment plants. Activated carbons (ACs) and other adsorbents, including naturally occurring materials (wood, keratin) are considered as nanomaterials (NMs) reference for the separation of organic pollutants. It is generally acknowledged that mass-transfer phenomena control sorption kinetics at the liquid/solid interface, with retention controlled by the sorbent/sorbate properties. Therefore, the type of interaction (strong or weak van der Waals forces) and the hydrophilic/hydrophobic properties of the adsorbent are two crucial factors. Besides, EDCs and pharmaceutical compound sorption on such kinds of nanoporous solids depend on both the molecule size and charge density. The applications of nanomaterials on non-conservative methods, like advanced oxidation processes or AOPs (e.g., photocatalysis and Fenton reaction), are contemplated as more apt in comparison to conservative technology like reverse osmosis nanofiltration, and adsorption, etc. One of the reasons is that AOPs generate free radicals (hydroxyls), which are strong oxidants for the demineralization of organic compounds and the extreme case that hydroxyl radicals can attack any kinds of pollutants with the generation of only water and carbon dioxide as final products. AOPs may imply the use of NMs as either catalysts or photocatalysts, which improve the selective removal of the target pollutant. Therefore, various literature reviews have revealed that there is a timely need to upgrade the efficiency of the remediation approaches to protect the environment against EDCs and pharmaceuticals adequately. There is currently a lack of definitive risk assessment tools due to their complicated detection and associated insufficiency in the health risk database. Hence, our present review focuses on applying carbon-based nanomaterials to remove EDCs and pharmaceuticals from aqueous systems. The paper covers the effect of these pollutants and photocatalytic methods for treating these compounds in wastewater, along with their limitations and challenges, plausible solutions, and prospects of such techniques.

Effects of Veliparib on Microglial Activation and Functional Outcomes after Traumatic Brain Injury in the Rat and Pig.

The inflammation response induced by brain trauma can impair recovery. This response requires several hours to develop fully and thus provides a clinically relevant therapeutic window of opportunity. Poly(ADP-ribose) polymerase inhibitors suppress inflammatory responses, including brain microglial activation. We evaluated delayed treatment with veliparib, a poly(ADP-ribose) polymerase inhibitor, currently in clinical trials as a cancer therapeutic, in rats and pigs subjected to controlled cortical impact (CCI). In rats, CCI induced a robust inflammatory response at the lesion margins, scattered cell death in the dentate gyrus, and a delayed, progressive loss of corpus callosum axons. Pre-determined measures of cognitive and motor function showed evidence of attentional deficits that resolved after three weeks and motor deficits that recovered only partially over eight weeks. Veliparib was administered beginning 2 or 24 h after CCI and continued for up to 12 days. Veliparib suppressed CCI-induced microglial activation at doses of 3 mg/kg or higher and reduced reactive astrocytosis and cell death in the dentate gyrus, but had no significant effect on delayed axonal loss or functional recovery. In pigs, CCI similarly induced a perilesional microglial activation that was attenuated by veliparib. CCI in the pig did not, however, induce detectable persisting cognitive or motor impairment. Our results showed veliparib suppression of CCI-induced microglial activation with a delay-to-treatment interval of at least 24 h in both rats and pigs, but with no associated functional improvement. The lack of improvement in long-term recovery underscores the complexities in translating anti-inflammatory effects to clinically relevant outcomes.

Emerging trends in photodegradation of petrochemical wastes: a review.

Various human activities like mining and extraction of mineral oils have been used for the modernization of society and well-beings. However, the by-products such as petrochemical wastes generated from such industries are carcinogenic and toxic, which had increased environmental pollution and risks to human health several folds. Various methods such as physical, chemical and biological methods have been used to degrade these pollutants from wastewater. Advance oxidation processes (AOPs) are evolving techniques for efficient sequestration of chemically stable and less biodegradable organic pollutants. In the present review, photocatalytic degradation of petrochemical wastes containing monoaromatic and poly-aromatic hydrocarbons has been studied using various heterogeneous photocatalysts (such as TiO2, ZnO and CdS. The present article seeks to offer a scientific and technical overview of the current trend in the use of the photocatalyst for remediation and degradation of petrochemical waste depending upon the recent advances in photodegradation of petrochemical research using bibliometric analysis. We further outlined the effect of various heterogeneous catalysts and their ecotoxicity, various degradation pathways of petrochemical wastes, the key regulatory parameters and the reactors used. A critical analysis of the available literature revealed that TiO2 is widely reported in the degradation processes along with other semiconductors/nanomaterials in visible and UV light irradiation. Further, various degradation studies have been carried out at laboratory scale in the presence of UV light. However, further elaborative research is needed for successful application of the laboratory scale techniques to pilot-scale operation and to develop environmental friendly catalysts which support the sustainable treatment technology with the "zero concept" of industrial wastewater. Nevertheless, there is a need to develop more effective methods which consume less energy and are more efficient in pilot scale for the demineralization of pollutant.

Striatal cholinergic cell ablation attenuates L-DOPA induced dyskinesia in Parkinsonian mice.

3,4-Dihydroxyphenyl-L-alanine (L-DOPA)-induced dyskinesia (LID) is a debilitating side effect of long-term dopamine replacement therapy in Parkinson's Disease. At present, there are few therapeutic options for treatment of LID and mechanisms contributing to the development and maintenance of these drug-induced motor complications are not well understood. We have previously shown that pharmacological reduction of cholinergic tone attenuates the expression of LID in parkinsonian mice with established dyskinesia after chronic L-DOPA treatment. The present study was undertaken to provide anatomically specific evidence for the role of striatal cholinergic interneurons by ablating them before initiation of L-DOPA treatment and determining whether it decreases LID. We used a novel approach to ablate striatal cholinergic interneurons (ChIs) via Cre-dependent viral expression of the diphtheria toxin A subunit (DT-A) in hemiparkinsonian transgenic mice expressing Cre recombinase under control of the choline acetyltransferase promoter. We show that Cre recombinase-mediated DT-A ablation selectively eliminated ChIs when injected into striatum. The depletion of ChIs markedly attenuated LID without compromising the therapeutic efficacy of L-DOPA. These results provide evidence that ChIs play a key and selective role in LID and that strategies to reduce striatal cholinergic tone may represent a promising approach to decreasing L-DOPA-induced motor complications in Parkinson's disease.

ß-Lactam synthon-interceded diastereoselective synthesis of functionalized octahydroindole-based molecular scaffolds and their in vitro cytotoxic evaluation.

A convenient and unprecedented synthesis of functionally enriched octahydroindole-based scaffolds has been developed via inter- and intra-molecular amidolysis of C-3 functionalized ß-lactams. The cytotoxic evaluation on oesophageal cancer cell line WHCO1 has revealed 7d as the most potent of the test compounds exhibiting an IC(50) value of 12.97 µM. The developed strategy further assumes significance as it entails the preparation of highly functionalized indoles without the aid of transition metal catalysis or pre-functionalization of substrates.

Azide-alkyne cycloaddition en route to novel 1H-1,2,3-triazole tethered isatin conjugates with in vitro cytotoxic evaluation.

1H-1,2,3-triazole tethered isatin conjugates have been synthesized and evaluated for cytotoxicity on four human cancer cell lines. The results revealed 5a, 5c, 5e and 5n proved to be twice as potent as 5-fluorouracil on THP-1 cell line with 5a and 5c being most active exhibiting IC(50) values of <1 against all cell lines except Caco-2. Activity profiles showed dependence on the substituents on isatin rings with a preference for hydrogen while a strong electron withdrawing fluoro as well as nitro substituents on either ring decreased the anticancer activity.