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Diclofenac is a widely prescribed anti-inflammatory drug having cardiovascular complications as one of the main liabilities that restrict its therapeutic use. We aimed to investigate for any role of rutin against diclofenac-induced cardiac injury with underlying mechanisms as there is no such precedent to date. The effect of rutin (10 and 20 mg/kg) was evaluated upon concomitant oral administration for fifteen days with diclofenac (10 mg/kg). Rutin significantly attenuated diclofenac-induced alterations in the serum cardiac markers (LDH, CK-MB, and SGOT), serum cytokine levels (TNF-α and IL-6), and oxidative stress markers (MDA and GSH) in the cardiac tissue. Histopathological examination and Scanning Electron Microscopy (SEM) findings displayed a marked effect of rutin to prevent diclofenac-mediated cardiac injury. Altered protein expression of myocardial injury markers (cTnT, FABP3, and ANP) and apoptotic markers (Bcl-2 and Caspase-3) in the cardiac tissue upon diclofenac treatment was considerably shielded by rutin treatment. MYL3 was unaffected due to diclofenac or rutin treatment. Rutin also significantly improved diclofenac-induced gastrointestinal and hepatic alterations based on the observed ameliorative effects in key mediators, oxidative stress markers, histopathology examination, and SEM findings. Overall results suggest that rutin can protect the diclofenac-induced cardiac injury by lowering oxidative stress, inhibiting inflammation, and reducing apoptosis. Further research work directs toward the development of phytotherapeutics for cardioprotection.

To study magnetoreception of Arabidopsis thaliana, we analysed several developmental responses including cryptochrome-independent seed germination and the phytochrome- and cryptochrome-dependent hypocotyl elongation and photo-accumulation of anthocyanins and chlorophylls in weak static magnetic fields ranging from near null to 122 μT. A field of 50 μT accelerated seed germination by about 20 h relative to samples maintained in a near-null field. The double mutant, cry1cry2, lacking cryptochromes 1 and 2 displayed the same magnetic field-induced germination acceleration under blue light as the wild-type strain. Magnetic field-induced germination acceleration was masked in the presence of exogenous sucrose. Stimulus-response curves for hypocotyl elongation in a range between near-null to 122 μT indicated maxima near 9 and 60 μT for the wild-type strain as well as mutant cry1cry2. The photo-accumulation of anthocyanins and chlorophylls could be effectively modulated by magnetic fields in the presence of low-irradiance red and blue light, respectively. The findings indicate that Arabidopsis thaliana possesses light-independent mechanisms of magnetic field reception, which remain presently unidentified. Our results are in better agreement with predictions of the level crossing mechanism (LCM) of magnetoreception rather than those of the cryptochrome-associated radical-pair mechanism (RPM)., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Bedaquiline (BDQ) is a new class of anti-tubercular (anti-TB) drugs and is currently reserved for multiple drug resistance (MDR-TB). However, after receiving fast-track approval, its clinical studies demonstrate that its treatment is associated with hepatotoxicity and labeled as 'boxed warning' by the USFDA. No data is available on BDQ to understand the mechanism for drug-induced liver injury (DILI), a severe concern for therapeutic failure/unbearable tolerated toxicities leading to drug resistance. Therefore, we performed mechanistic studies to decipher the potential of BDQ at three dose levels (80 to 320 mg/kg) upon the repeated dose administration orally using a widely used mice model for TB. Results of BDQ treatment at the highest dose level showed that substantial increase of hepatic marker enzymes (SGPT and SGOT) in serum, oxidative stress marker levels (MDA and GSH) in hepatic tissue, and pro-inflammatory cytokine levels (TNF-α, IL-6, and IL-1β) in serum compared to control animals. Induction of liver injury situation was further evaluated by Western blotting for various protein expressions linked to oxidative stress (SOD, Nrf2, and Keap1), inflammation (NF-ĸB and IKKβ), apoptosis (BAX, Bcl-2, and Caspase-3) and drug metabolism enzymes (CYP3A4 and CYP2E1). The elevated plasma level of BDQ and its metabolite (N-desmethyl BDQ) were observed, corresponding to BDQ doses. Histopathological examination and SEM analysis of the liver tissue corroborate the above-mentioned findings. Overall results suggest that BDQ treatment-associated generation of its cytotoxic metabolite could act on CYP2E1/NF-kB pathway to aggravate the condition of oxidative stress, inflammation, and apoptosis in the liver and precipitating hepatotoxicity., Competing Interests: Declaration of competing interest The authors have no potential conflict of interest to declare., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Rumex abyssinicus Jacq. is a perennial medicinal herb widely used in traditional medicine to treat many diseases. Phytochemicals of the plant were isolated using column chromatography and thin layer chromatography techniques. Extract, fractions and pure compounds were screened for antimicrobial activity against sensitive and multi-drug resistant microbes and their cytotoxicity was performed on different cancer cell lines. The mechanism of action of purified helminthosporin as well as the potent fraction containing a mixture of two compounds was assessed. Fraction R7C3 was the most potent antibacterial with the lowest MIC value of 0.12 µg/mL. Helminthosporin was the most potent compound with the lowest MIC value of 1.95 µg/mL. The compound was more potent than the antibiotic chloramphenicol against multi-drug resistant (MDR) bacteria with MIC equal to 16 µg/mL. The fraction and helminthosporin were shown to destroy the cell wall of the yeast and bacteria, and DNA fragmentation effect on the genome of Candida albicans and Bacillus cereus. Helminthosporin was the most cytotoxic compound with IC 50  ˂ 10 µM. Fraction R7C3 showed the most potent cytotoxic effects on all cancer cell lines, with IC 50 ranging from ˂1 to 4.35 ng/mL. Our study is the first report on the mechanism of action of helminthosporin, a potent candidate in the development of new drugs against multi-resistant bacteria and cancer cells. In addition, this study uncovered Rumex abyssinicus as a new source of syringic acid and bis(2-ethyloctyl) phthalate., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Potato is constantly exposed to various kinds of phytopathogens which cause diseases during the developmental stage and post-harvest storage. This investigation was designed to assay the anti-phytopathogen activity of bacterial endophytes and their suppressive effects on rot disease in potato. The study also aimed to screen isolates for their plant growth-promoting traits and establish GC-MS-based metabolite profile of the potent isolate. Endophytes were isolated from Rumex dentatus and identified based on 16S rRNA gene. They were screened in dual culture assay against fungal phytopathogens and the potent isolate was tested for its capability to suppress Fusarium rot disease in potato tubers. The mechanism of action of endophytes on the phytopathogens was assessed using scanning electron microcopy. Isolates were also screened in vitro to assay their capability to produce phytohormones, hydrolytic enzymes, and to solubilize phosphates. Endophytic isolates produced proteases with a diameter of halo zone ranging from 7 to 32 mm. Bacillus sp. KL5 exhibited the highest production of indole acetic acid (IAA) with the amount of 104.28 µg/mL and was the most potent antagonist of Fusarium oxysporum and Verticillium dahliae with an inhibitory percentage of 61.53 and 100%, respectively. It showed a reduction of potato rot disease severity by more than 50%. GC-MS of active fractions of KL5 showed the presence of dibutylphthalate and 2,4-di-tert-butylphenol as major metabolites. From this study, it is evident that endophytic Bacillus species from R. dentatus are potent antagonists of F. oxysporum and V. dahliae. Bacillus sp. KL5 is a potent inhibitor of pathogenic F. oxysporum in potato tubers and can be developed as a biocontrol agent., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The study was planned to assess the acute toxicity of textile industry intermediate, 2 amino benzene sulfonate (2 ABS) through biochemical, genotoxic, histopathological and ultrastructural (SEM) analysis in liver and gills of fresh water fish Channa punctatus. The fish were subjected to two sublethal concentrations (2.83 mg/30 g b. w. and 5.66 mg/30 g b. w.) for 96 h. A significant (p ≤ 0.05) increment in the enzymatic activity of catalase (CAT), superoxide dismutase (SOD) and glutathione reductase (GR) was observed followed by decline on CAT-SOD after 96 h of exposure in both the tissues, whereas increment in malondialdehyde (MDA) levels were observed throughout the exposure period for both the concentrations. Comet assay also showed elevated tail length and % tail DNA throughout the exposure period, marking maximum damage after 96 h for both the tissues. Light microscopy divulged several anomalies including: infiltration of lymphocytes, sinusoidal dilations, necrosis, vacuolation in liver and secondary lamellae fusion, telangiectasia and epithelial uplifting in gills. The highest degree of tissue change (DTC) in liver (50.33 ± 0.88) and gill (42.33 ± 2.18) was recorded with the highest concentration after 96 h of exposure. Scanning electron microscopy (SEM) also reaffirmed several alterations in liver and gills of fish. The findings of the present study inflict changes in liver and gills, marking the interference of 2 ABS with the normal functioning by suppressing the enzymatic activity, accelerating the lipid peroxidation, enhancing DNA damage and by disrupting normal architecture of liver and gills, making it toxic towards the fish even at sub-lethal concentrations., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Endocrine disruptors (EDs) disrupt the standard operation of the endocrine systems, resulting in untoward effects. EDs have gained extensive consideration due to their severe adverse impacts on public and wildlife health. A variety of compounds from both natural and synthetic origin may cause endocrine disruptions. These may be found in industrial chemicals, persistent organic pollutants, and products of regular use including pharmaceuticals, medical equipment, implants, medical/surgical and dental devices, cosmetics, food products, other consumer goods, their packaging and processing materials. Apart from direct consumption or use, these chemicals may impact by entering our food chain or ecosystem. These chemicals act by mimicking the hormones or blocking their receptors or interfering in their normal production, absorption, distribution, metabolism and excretion. The implementation of a regulatory framework on the complex multidisciplinary field of EDs brings enormous challenges, which pose barriers to the regulatory process. This study aims to focus on the key public and ecological health concerns presented by EDs, challenges faced by regulators to achieve successful regulatory proposition and the importance of collaboration endeavours to potentially conquer such challenges. Endocrine-disrupting chemicals (EDCs) or EDs can impact at low exposure levels, bringing about a broad range of health issues including disorders related to reproductive, fetal development, neurological, immunological, metabolic and cancer, etc. They may cause health effects across generations. The regulatory frameworks available across major regulators are tackling the identification of EDs and their mechanisms to provide necessary guidance on the safety and disposal of such substances. However, the challenges faced outweigh the regulatory mechanisms in place. The major challenges are related to structural ranges at times leading to no representative structures, active metabolites, substantiate quantum, delayed effects, epigenetic changes, widespread existence, concentration correlation for different biological species, availability of appropriate methods, exposure to a mixture of chemicals, complex endocrinology principles, unknown sources, routes and mechanisms, impacts at early stages of life, geographical movement of EDs, hazard-based vs. risk-based approaches. Regulators of healthcare and environmentalists needs to collaborate amongst them and with wider stakeholders including industry sponsors to find ways of dealing with such challenges and capitalize on the research-based knowledge grid available across institutions. Existence of EDs, their impact on living beings and mechanism of influence are like a tangled web, which induces difficulties in regulating them with conventional mindset. Conquering these challenges necessitates that regulators should join forces amongst themselves, with other institutions operating for environment, with industry sponsors and researchers to achieve success in public health safety., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Magnetic-field reception of animals and plants is currently discussed in the framework of a cryptochrome-based radical-pair mechanism. Efforts to unravel magnetoreception in plants suffered historically from several shortcomings, most prominently, the conspicuous absence of detailed stimulus-response relationships. To determine the sensitivity of seedlings of Arabidopsis thaliana to weak static magnetic fields we generated stimulus-response curves between near zero and 188 μT for the transcript levels of the genes rbcl, cab4, pal4 and ef1. The moderate magneto-responsiveness of dark-grown seedlings was greatly enhanced under blue light, and for rbcl and pal4 also under red light. The stimulus-response curves obtained under blue light of constant photon-fluence rate displayed multiple maxima and thus a pattern fundamentally different from that prevalent in plant and animal physiology. A double mutant lacking cryptochromes 1 and 2 displayed altered stimulus-response curves without losing, however, magneto-responsiveness completely. A reversal of the magnetic field direction substantially affected the gene expression and the quantity of CAB-protein (chlorophyll a,b-binding protein). The majority of our results are at variance with the notion of cryptochromes acting as the only magnetic-field sensors. They do not, however, exclude the possibility that cryptochromes participate in the magnetic field reception of Arabidopsis. The findings have the unexpected implication that cryptochrome- and phytochrome-mediated plant responses can be modulated by the strength and the orientation of the local geomagnetic field., (Copyright © 2018 Elsevier GmbH. All rights reserved.)

Hydrothermal liquefaction of lignin was performed using methanol and ethanol at various temperatures (200, 250 and 280°C) and residence times of 15, 30 and 45min. Maximum liquid product yield (85%) was observed at 200°C and 15min residence time using methanol. Increase in temperature was seen to decrease the liquid products yield. With increase in residence time, liquid yields first increased and then decreased. FTIR and (1)H NMR showed the presence of substituted phenols and aromatic ethers in liquid products and breakage of β-O-4 or/and α-O-4 ether bonds present in lignin during hydrothermal liquefaction was confirmed through FTIR of bio-residue. In comparison to the existing literature information, higher lignin conversion to liquid products and maximum carbon conversion (72%) was achieved in this study., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Although the amnestic effects of alcohol in humans are well known, its effects on emotional memory are unclear. In this study, using a randomized double-blind placebo-controlled design, we examine narrative emotional episodic memory in healthy human female volunteers (n=32) who received either a single dose of alcohol (0.6g/kg), or a placebo and then viewed neutral story elements presented in either a neutral or emotional context. Memory was tested for gist and detail of the neutral elements 3days later in a surprise recognition test. Since alcohol modulates GABAergic neurotransmission and may exert its effects on emotion through the limbic system, we predicted that acute alcohol treatment would reduce the expected emotional memory-advantage for gist, leaving detail memory relatively unaffected. Furthermore, given previous findings showing that 'primacy' memory is enhanced by physiological arousal, we predicted that reduced arousal produced by alcohol would have the opposite effect and impair primacy memory relative to the middle or 'recency' sections of the narrative. Emotional arousal was expected to oppose this effect, so impaired primacy memory following alcohol was only expected in the neutral version of the narrative. Although there was a main effect of story phase (though not of story version), contrary to expectations, alcohol impaired primacy memory for emotionally encoded neutral material. The results suggest that under certain circumstances emotional context or physiological arousal make memories labile and susceptible to disruption through pharmacological manipulation during encoding., (2009 Elsevier Inc. All rights reserved.)

Background: Epidemiological evidence suggests a link between cannabis use and psychosis. A variety of factors have been proposed to mediate an individual's vulnerability to the harmful effects of the drug, one of which is their psychosis proneness. We hypothesized that highly psychosis-prone individuals would report more marked psychotic experiences under the acute influence of cannabis., Method: A group of cannabis users (n=140) completed the Psychotomimetic States Inventory (PSI) once while acutely intoxicated and again when free of cannabis. A control group (n=144) completed the PSI on two parallel test days. All participants also completed a drug history and the Schizotypal Personality Questionnaire (SPQ). Highly psychosis-prone individuals from both groups were then compared with individuals scoring low on psychosis proneness by taking those in each group scoring above and below the upper and lower quartiles using norms for the SPQ., Results: Smoking cannabis in a naturalistic setting reliably induced marked increases in psychotomimetic symptoms. Consistent with predictions, highly psychosis-prone individuals experienced enhanced psychotomimetic states following acute cannabis use., Conclusions: These findings suggest that an individual's response to acute cannabis and their psychosis-proneness scores are related and both may be markers of vulnerability to the harmful effects of this drug.