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Gastric ulcer (GU) is the most common health concern that occurs due to alcohol consumption, smoking and physiological stress. Ethanol-induced GU in animal model resembles the pathophysiology of human ulcer. The present study was designed to investigate the cytoprotective and anti-inflammatory properties of tert-butylhydroquinone (tBHQ), a nuclear factor erythroid 2-related factor 2 (Nrf2) activator, against gastric mucosal damage induced by acute exposure of ethanol (5 ml/kg). The intervention of tBHQ (25 and 50 mg/kg, per os (po)) and omeprazole (20 mg/kg, po) was done for 10 consecutive days. Omeprazole was chosen as a standard drug because it is prescribed for the treatment of GU. Pretreatment of tBHQ decreased gastric mucosal lesion, ulcer index, apoptotic cells and lipid peroxidation level induced by ethanol. Furthermore, the intervention of tBHQ increased gastric mucosa integrity, pH, reduced glutathione, collagen and mucus-producing goblet cells. Intervention of tBHQ increased the expression of antioxidant markers such as Nrf2, haeme oxygenase-1 and catalase and decreased the expressions of inflammatory markers such as nuclear factor kappa-light-chain-enhancer of activated B cells and cyclooxygenase-2. The cytoprotective potential of tBHQ against gastric mucosal damage might be due to its ability to enhance cellular antioxidants and anti-inflammatory responses. [ABSTRACT FROM AUTHOR]

Background: Arteriovenous fistula (AVF) failure is a prevalent concern for patients with end-stage kidney disease on hemodialysis. Recognizing the efficacy of ultrasound Doppler in post-operative AVF evaluation, this study sought to discern the predictive capabilities of various ultrasonographic and color-Doppler metrics for early AVF outcomes., Methods: This single-center, prospective cohort study spanned 1 year and, post ethical clearance, included all patients who underwent native AVF creation surgery and were subsequently referred for standard post-operative ultrasound Doppler assessment. Parameters such as fistula size, cephalic vein area and diameter, and AVF flow velocity and rates were assessed on post-operative day 2, week 2, and week 6. These initial findings were juxtaposed with later outcomes to determine unassisted AVF results., Results: Of the initial cohort of 40 patients, 75% encountered AVF failure, whereas 25% realized successful unassisted AVF maturation. A notable observation was the significant variance in AVF flow rates as early as post-operative day 2. A threshold of >246 ml/min was indicative of successful unassisted AVF maturation, leading to a sensitivity of 80% and a specificity of 70%. Although the cephalic vein diameter on post-operative day 2 lacked a robust association with AVF outcomes, a cut-off of >3.4 mm, when combined with flow rate testing, augmented the cumulative sensitivity to 92%., Conclusion: Ultrasound Doppler stands out as a valuable quantitative imaging modality, adept at prognosticating AVF outcomes from as early as post-operative day 2. In particular, a flow rate exceeding 246 ml/min and a cephalic vein diameter surpassing 3.4 mm are salient indicators for the early prediction of successful AVF outcomes., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Phase-change memory (PCM) relies on the characteristics of phase-change materials that exhibit slow resistance state changes and enable multilevel operation with minimal resistance drift. They are emerging as promising candidates for artificial intelligence applications inspired by neuroscience and require high volumes of data. However, achieving the necessary qualities, such as thermal stability and fast operation speed, simultaneously is still a major obstacle for PCM materials. The present study investigated the linear and nonlinear optical and electronic properties of Te (1- x ) (GeSe 0.5 )Y x ( x = 0.05, 0.1, 0.15) thin films deposited via a thermal evaporation technique by structural characterization (using XRD), surface morphology analysis (using SEM), and elemental composition analysis (using EDX). Transmission spectra ranging from 500 to 2500 nm were obtained using a UV-visible spectrophotometer to determine the optical properties. The refractive index ( n ) and extinction coefficient ( k ) were also determined, and Tauc's relationship was applied to assess the optical absorption data. The absorption coefficient ( α ) was determined utilizing the Urbach relation. The Wemple-DiDomenico model was employed to calculate the nonlinear refractive index. Furthermore, the dielectric properties, loss tangent, and surface/volume energy loss functions were determined. The optical energy bandgap of the thin films revealed the allowed indirect transitions. The observed enhancement of the optical parameters suggested that the investigated composition is appropriate for different photonic applications., Competing Interests: The authors declare no competing interests., (This journal is © The Royal Society of Chemistry.)

The photocatalytic oxidation and generation/regeneration of amines to imines and leucodopaminechrome (LDC)/NADH are subjects of intense interest in contemporary research. Imines serve as crucial intermediates for the synthesis of solar fuels, fine chemicals, agricultural chemicals, and pharmaceuticals. While significant progress has been made in developing efficient processes for the oxidation and generation/regeneration of secondary amines, the oxidation of primary amines has received comparatively less attention until recently. This discrepancy can be attributed to the high reactivity of imines generated from primary amines, which are prone to dehydrogenation into nitriles. In this study, we present the synthesis and characterization of a novel polymer-based photocatalyst, denoted as PMMA-DNH, designed for solar light-harvesting applications. PMMA-DNH incorporates the light-harvesting molecule dinitrophenyl hydrazine (DNH) at varying concentrations (5%, 10%, 20%, 30%, and 40%). Leveraging its high molar extinction coefficient and slow charge recombination, the 30% DNH-incorporated PMMA photocatalyst proves to be particularly efficient. This photocatalytic system demonstrates exceptional yields (96.5%) in imine production and high generation/regeneration rates for LDC/NADH (65.27%/78.77%). The research presented herein emphasizes the development and application of a newly engineered polymer-based photocatalyst, which holds significant promise for direct solar-assisted chemical synthesis in diverse commercial applications., (© 2023 American Society for Photobiology.)

Prostate cancer poses significant diagnostic challenges, with conventional methods like prostate-specific antigen (PSA) screening and transrectal ultrasound (TRUS)-guided biopsies often leading to overdiagnosis or miss clinically significant cancers. Multiparametric MRI (mpMRI) has emerged as a more reliable tool. However, it is limited by high inter-observer variability and radiologists missing up to 30% of clinically significant cancers. This article summarizes a few of these recent advancements in quantitative MRI techniques that look at the "Virtual Pathology" of the prostate with an aim to enhance prostate cancer detection and characterization. These techniques include T2 relaxation-based techniques such as luminal water imaging, diffusion based such as vascular, extracellular, and restricted diffusion for cytometry in tumors (VERDICT) and restriction spectrum imaging or combined relaxation-diffusion techniques such as hybrid multi-dimensional MRI (HM-MRI), time-dependent diffusion imaging, and diffusion-relaxation correlation spectrum imaging. These methods provide detailed insights into underlying prostate microstructure and tissue composition and have shown improved diagnostic accuracy over conventional MRI. These innovative MRI methods hold potential for augmenting mpMRI, reducing variability in diagnosis, and paving the way for MRI as a 'virtual histology' tool in prostate cancer diagnosis. However, they require further validation in larger multi-center clinical settings and rigorous in-depth radiological-pathology correlation are needed for broader implementation., (© 2024. The Author(s), under exclusive licence to European Society for Magnetic Resonance in Medicine and Biology (ESMRMB).)

Globally, more than 5 billion tons of crop residue (mainly rice straw) are produced yearly, and their management results in pollution, which kills microbes and limits soil nutrient recycling. Therefore, on-farm management that boosts degradation speed will improve the practicability of crop residue retention practices. The present study evaluated the 21 microbial isolates ( Pseudomonas, Bacillus , Aspergillus, Trichoderma, Fusarium, and Rhizopus ) from the soil of different agroclimatic zones obtained from rice fields for in situ straw degradation. The microbial diversity of these isolates was analyzed using 16 s rRNA and 18 s rRNA primers from various soil samples. The rice straw was used for degradation from isolated pathogens individually and in combination, and the results were analyzed using FTIR (Fourier transform infrared spectroscopy). The result suggested that the straw's degradation was the maximum with Trichoderma and Aspergillus, followed by the mixture of the isolates ( Pseudomonas, Bacillus , Aspergillus, Trichoderma, Fusarium, and Rhizopus ). Furthermore, SEM (scanning electron microscope) observed the degradation rate on different days of inoculation (7, 14, 28, 56, 70, and 100 DAI). The results showed that 90 DAI caused the highest degradation of rice straw. Therefore, Trichoderma containing microbial consortia could be used for vermicompost production from rice straw in field conditions, and it could increase crop productivity. Overall, our study added knowledge in rice straw management through a microbial consortium for better utilization in predominantly rice-growing countries., Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-024-03982-z., Competing Interests: Conflict of interestsOn behalf of all authors, the corresponding author states that there is no conflict of interest., (© King Abdulaziz City for Science and Technology 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Objective: Boldine is a plant-derived bioactive compound that has a beneficial impact on human health. Boldine is an aporphine alkaloid mainly obtained from the leaves and bark of the Chilean Boldo tree ( Peumus boldus , Family: Monimiaceae). There are plenty of preclinical evidence supports that boldine exerts its beneficial effects against various diseases. Lumiskin™, a patented and marketed formulation by Revitol Skincare for skin brightening, contains Dicetyl boldine, a boldine derivative., Content: All the available information on the Chilean boldo tree ( P. boldus Molina) species was actualized by systematically searching the scientific databases (PubMed, SciFinder, Web of Science, Google Scholar, Scopus and others) and scientific literature. This article covers the recent advances in pharmacokinetic, toxicological, pharmacological/biological activities, and molecular mechanisms of the bioactive compound to understand health benefits of boldine better., Summary: Boldine exerts antioxidant, hepatoprotective, anti-atherosclerotic, anti-diabetic, analgesic, antipyretic, anti-inflammatory, anti-epileptic, neuroprotective, nephroprotective, anti-arthritis, anticancer and nootropic effects. Moreover, boldine exhibits its various pharmacological activities by altering antioxidant parameters (MDA, superoxide dismutase, glutathione), peroxynitrite, inflammatory markers apoptotic index, caspase-3, acetyl-cholinesterase, myeloperoxidase, TNF-α (Tumor necrosis factor-α), iNOS, Bcl-2-associated X protein (BAX), ACE-1(Angiotensin-converting enzyme-1), dopamine D2 receptors and nicotinic acetylcholine receptor. Boldine has the potential to modulate a variety of biological networks., Outlook: Due to its versatile pharmacological effects reported in various experimental animals as well as in randomized clinical trials for the treatment of facial melasma and for treatment of urinary stone lithotripsy in children as a complementary phytotherapy; in the future, this compound might be developed as a novel drug for a different indication., (© 2024 Walter de Gruyter GmbH, Berlin/Boston.)

Indeed, the development of ecologically benign molecular fabrication methods for highly efficient graphene quantum dots-based photocatalysts is of great significant. Graphene quantum dots-based photocatalysts have promising applications in various field, including environmental remediation, energy conversion, and splitting of water. However, ensuring resource reusability and minimizing the environmental impact are crucial considerations in the development. From this perspective, attention has also been paid to the creation of easy to make solar light harvesting graphene quantum dots-based photocatalysts for synthesising pharmaceuticals and functional imines compounds. Imines are excellent significant building blocks in pharmaceutical chemistry and excellent examples of these valuable compounds' synthetic intermediates, and the environmentally friendly oxidative synthesis of imines from amines. Therefore, herein, we designed a facile and efficient condensation route to synthesize the Nen-GQDs@PH photocatalyst. This route involves coupling of 2,4-dinitrophenylhydrazine (PH) with nitrogen-enriched graphene quantum dots (Nen-GQDs). The Nen-GQDs@PH as photocatalyst functions in a highly selective and efficient manner, leading to high amines conversion efficiency to imines (95%). Our results highlight a novel and environmentally safe approach for generating highly selective imines from various types of amines, setting a new benchmark in the current research field., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Liver fibrosis is a typical pathological state/stage involved in most chronic liver diseases and its persistence results in cirrhosis. Inflammasomes are cytoplasmic sensors that induce inflammation in response to stress. Glibenclamide (GLB) is an USFDA-approved drug for type 2 diabetes and is reported to possess anti-inflammatory activity by inhibiting inflammatory cytokines. Dimethyl fumarate (DMF) is an USFDA-approved drug for multiple sclerosis and has been reported to activate the Nrf2/ARE pathway to maintain the cellular antioxidant balance. A total of 36 rats were randomized into six groups ( n  = 6 each). The rats were injected with thioacetamide (TAA) 200 mg/kg, intraperitoneally every third day for eight consecutive weeks to induce liver fibrosis and oral treatment of GLB 0.5 mg/kg/day and DMF 25 mg/kg/day, and their combinations were provided for the last four consecutive weeks. Treatment with GLB, DMF, and GLB+DMF significantly protected against TAA-mediated oxidative stress and inflammatory conditions by improving hepatic function test, triglycerides, hydroxyproline, and histopathological alterations, by inhibiting the NLRP3 inflammasome signaling and fibrogenic markers, and by activating Nrf2/ARE pathway in Wistar rats. The present results suggest that simultaneous Nrf2/ARE activation and NLRP3 inflammasome inhibition could significantly contribute to developing a novel therapy for patients with liver fibrosis., Competing Interests: The authors declare that they have no conflict of interest.

Lead toxicity is a barrier to the widespread commercial manufacture of lead halide perovskites and their use in solar photovoltaic (PV) devices. Eco-friendly lead-free perovskite solar cells (PSCs) have been developed using certain unique non- or low-toxic perovskite materials. In this context, Sn-based perovskites have been identified as promising substitutes for Pb-based perovskites due to their similar characteristics. However, Sn-based perovskites suffer from chemical instability, which affects their performance in PSCs. This study employs theoretical simulations to identify ways to improve the efficiency of Sn-based PSCs. The simulations were conducted using the SCAPS-1D software, and a lead-free, non-toxic, and inorganic perovskite absorber layer (PAL), i.e. CsSnI 3 was used in the PSC design. The properties of the hole transport layer (HTL) and electron transport layer (ETL) were tuned to optimize the performance of the device. Apart from this, seven different combinations of HTLs were studied, and the best-performing combination was found to be ITO/PCBM/CsSnI 3 /CFTS/Se, which achieved a power conversion efficiency (PCE) of 24.73%, an open-circuit voltage ( V OC ) of 0.872 V, a short-circuit current density ( J SC ) of 33.99 mA cm -2 and a fill factor (FF) of 83.46%. The second highest PCE of 18.41% was achieved by the ITO/PCBM/CsSnI 3 /CuSCN/Se structure. In addition to optimizing the structure of the PSC, this study also analyzes the current density-voltage ( J - V ) along with quantum efficiency (QE), as well as the impact of series resistance, shunt resistance, and working temperature, on PV performance. The results demonstrate the potential of the optimized structure identified in this study to enhance the standard PCE of PSCs. Overall, this study provides important insights into the development of lead-free absorber materials and highlights the potential of using CsSnI 3 as the PAL in PSCs. The optimized structure identified in this study can be used as a base for further research to improve the efficiency of Sn-based PSCs., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (This journal is © The Royal Society of Chemistry.)

Perovskite solar cells (PSCs) have become a possible alternative to traditional photovoltaic devices for their high performance, low cost, and ease of fabrication. Here in this study, the SCAPS-1D simulator numerically simulates and optimizes CsPbBr 3 -based PSCs under the optimum illumination situation. We explore the impact of different back metal contacts (BMCs), including Cu, Ag, Fe, C, Au, W, Pt, Se, Ni, and Pd combined with the TiO 2 electron transport layer (ETL) and CFTS hole transport layer (HTL), on the performance of the devices. After optimization, the ITO/TiO 2 /CsPbBr 3 /CFTS/Ni structure showed a maximum power conversion efficiency (PCE or η ) of 13.86%, with Ni as a more cost-effective alternative to Au. After the optimization of the BMC the rest of the investigation is conducted both with and without HTL mode. We investigate the impact of changing the thickness and the comparison with acceptor and defect densities (with and without HTL) of the CsPbBr 3 perovskite absorber layer on the PSC performance. Finally, we optimized the thickness, charge carrier densities, and defect densities of the absorber, ETL, and HTL, along with the interfacial defect densities at HTL/absorber and absorber/ETL interfaces to improve the PCE of the device; and the effect of variation of these parameters is also investigated both with and without HTL connected. The final optimized configuration achieved a V OC of 0.87 V, J SC of 27.57 mA cm -2 , FF of 85.93%, and PCE of 20.73%. To further investigate the performance of the optimized device, we explore the impact of the temperature, shunt resistance, series resistance, capacitance, generation rate, recombination rate, Mott-Schottky, JV , and QE features of both with and without HTL connected. The optimized device offers the best thermal stability at a temperature of 300 K. Our study highlights the potential of CsPbBr 3 -based PSCs and provides valuable insights for their optimization and future development., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (This journal is © The Royal Society of Chemistry.)

Background Cutaneous mucormycosis has shown a significant upsurge during the COVID-19 pandemic. Due to the rapid progression and high mortality of cutaneous mucormycosis in this context, it is important to identify it early. However, very few studies report detailed clinical descriptions of cutaneous mucormycosis in COVID-19 patients. Objectives To describe mucocutaneous lesions of COVID-19-associated mucormycosis based on clinical morphology and attempt to correlate them with radiological changes. Methods A retrospective cross-sectional study was conducted at a tertiary care centre from 1st April to 31st July 2021. Eligibility criteria included hospitalised adult patients of COVID-19-associated mucormycosis with mucocutaneous lesions. Results All subjects were recently recovering COVID-19 patients diagnosed with cutaneous mucormycosis. One of fifty-three (2%) patients had primary cutaneous mucormycosis, and all of the rest had secondary cutaneous mucormycosis. Secondary cutaneous mucormycosis lesions presented as cutaneous-abscess in 25/52 (48%), nodulo-pustular lesions in 1/52 (2%), necrotic eschar in 1/52 (2%) and ulcero-necrotic in 1/52 (2%). Mucosal lesions were of three broad sub-types: ulcero-necrotic in 1/52 (2%), pustular in 2/52 (4%) and plaques in 1/52 (2%). Twenty out of fifty-two patients (38%) presented with simultaneous mucosal and cutaneous lesions belonging to the above categories. Magnetic resonance imaging of the face showed variable features of cutaneous and subcutaneous tissue involvement, viz. peripherally enhancing collection in the abscess group, "dot in circle sign" and heterogeneous contrast enhancement in the nodulo-pustular group; and fat stranding with infiltration of subcutaneous tissue in cases with necrotic eschar and ulcero-necrotic lesions. Limitations The morphological variety of cutaneous mucormycosis patients in a single-centre study like ours might not be very precise. Thus, there is a need to conduct multi-centric prospective studies with larger sample sizes in the future to substantiate our morphological and radiological findings. Conclusions COVID-19-associated mucormycosis patients in our study presented with a few specific types of mucocutaneous manifestations, with distinct magnetic resonance imaging findings. If corroborated by larger studies, these observations would be helpful in the early diagnosis of this serious illness.

The prevalence of nonalcoholic fatty liver disease (NAFLD) is much higher in patients with type II diabetes (T2D). Inflammasomes are multimolecular complexes reported to involve inflammatory conditions. The nuclear factor (erythroid-derived 2)-like factor 2/antioxidant responsive element (Nrf2/ARE) pathway is an important regulator of antioxidant status in cells. Antidiabetic drug glibenclamide (GLB) is reported as  NACHT, leucine-rich repeat, and pyrin domain domains-containing protein 3 (NLRP3) inflammasome inhibitor, whereas anti-multiple sclerosis drug dimethyl fumarate (DMF) is reported as an Nrf2/ARE pathway activator. Both GLB and DMF possess anti-inflammatory and antioxidant properties, therefore, the hypothesis was made to look into the alone as well as the combination potential of GLB, DMF, and GLB + DMF, against NAFLD in diabetic rats. This study was aimed to investigate (1) the involvement of NLRP3 inflammasome and Nrf2/ARE signaling in diabetes-associated NAFLD (2) the effect of GLB, DMF, GLB + DMF, and metformin (MET) interventions on NLRP3 inflammasome and Nrf2/ARE signaling in diabetes-associated NAFLD. The rats were injected with streptozotocin (STZ) 35 mg/kg and fed a high-fat diet (HFD) for 17 consecutive weeks to induce diabetic NAFLD. The oral treatment of GLB 0.5 mg/kg/day, DMF 25 mg/kg/day, their combination and MET 200 mg/kg/day, were provided from the 6th to the 17th week. Treatment with GLB, DMF, GLB + DMF, and MET significantly alleviated HFD + STZ-induced plasma glucose, triglycerides, cholesterol, %HbA1c, hepatic steatosis, NLRP3, apoptosis-associated speck-like protein containing a caspase activation and recruitment domain, CARD, caspase-1, interleukin-1β (IL-1β), nuclear factor-κB (NF-κB), Nrf2, superoxide dismutase 1, catalase, IGF 1, heme oxygenase 1, receptor for the advanced glycation end product (RAGE), and collagen-1 in diabetic rats. Further, a mechanistic molecular study employing other specific NLRP3 inhibitors and Nrf2 activators will significantly contribute to the development of novel therapy for fatty liver diseases., (© 2023 Wiley Periodicals LLC.)

A novel surface plasmon resonance-based biosensor for SARS-CoV-2 virus is proposed in this article. The biosensor is a Kretschmann configuration-based structure that consists of CaF 2 prism as base, at which silver (Ag), TiO 2 , and MXene nanolayers are used to enhance the performance. Theoretically, the performance parameters have been investigated by means of Fresnel equations and transfer matrix method (TMM). The TiO 2 nanolayer not only prevents oxidation of Ag layer but also enhances the evanescent field in its vicinity. The sensor provides an ultrahigh angular sensitivity of 346°/RIU for the detection of SARS-CoV-2 virus. Some other performance parameters, including FWHM (full width at half maxima), detection accuracy (DA), limit of detection (LOD), and quality factor (QF) have also been calculated for proposed SPR biosensor with their optimized values 2.907°, 0.3439 deg -1 , 1.445 × 10 -5 , and 118.99 RIU -1 , respectively. The obtained results designate that the proposed surface plasmon resonance (SPR) based biosensor has notably enhanced angular sensitivity as compared to previous results reported in the literatures till date. This work may facilitate a significant biological sample sensing device for fast and accurate diagnosis at early stage of SARS-CoV-2 virus., Competing Interests: Conflict of InterestThe authors declare no competing interests., (© The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2023, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Solar cells based on lead-free perovskite have demonstrated great potential for next-generation renewable energy. The SCAPS-1D simulation software was used in this study to perform novel device modelling of a lead-free perovskite solar cell of the architecture ITO/WS 2 /CH 3 NH 3 SnI 3 /P3HT/Au. For the performance evaluation, an optimization process of the different parameters such as thickness, bandgap, doping concentration, etc., was conducted. Extensive optimization of the thickness and doping density of the absorber and electron transport layer resulted in a maximum power-conversion efficiency of 33.46% for our designed solar cell. Because of the short diffusion length and higher defect density in thicker perovskite, an absorber thickness of 1.2 µm is recommended for optimal solar cell performance. Therefore, we expect that our findings will pave the way for the development of lead-free and highly effective perovskite solar cells.

This paper describes the simulation by Solar Cell Capacitance Simulator-1D (SCAPS-1D) software of ZnO/CdS/SnS/NiO/Au solar cells, in which zinc oxide (ZnO) is used as transparent conductive oxide (TCO) and nickel oxide (NiO) is used as a hole transport layer (HTL). The effects of absorber layer (SnS) thickness, carrier concentration, SnS defect density, NiO HTL, ZnO TCO, electron affinity and work function on cell performance have been evaluated. The effect of interface defect density of SnS/CdS on the performance of the heterojunction solar cell is also analysed. As the results indicate, a maximum power conversion efficiency of 26.92% was obtained.

Current challenges of using serum prostate-specific antigen (PSA) level-based screening, such as the increased false positive rate, inability to detect clinically significant prostate cancer (PCa) with random biopsy, multifocality in PCa, and the molecular heterogeneity of PCa, can be addressed by integrating advanced multiparametric MR imaging (mpMRI) approaches into the diagnostic workup of PCa. The standard method for diagnosing PCa is a transrectal ultrasonography (TRUS)-guided systematic prostate biopsy, but it suffers from sampling errors and frequently fails to detect clinically significant PCa. mpMRI not only increases the detection of clinically significant PCa, but it also helps to reduce unnecessary biopsies because of its high negative predictive value. Furthermore, non-Cartesian image acquisition and compressed sensing have resulted in faster MR acquisition with improved signal-to-noise ratio, which can be used in quantitative MRI methods such as dynamic contrast-enhanced (DCE)-MRI. With the growing emphasis on the role of pre-biopsy mpMRI in the evaluation of PCa, there is an increased demand for innovative MRI methods that can improve PCa grading, detect clinically significant PCa, and biopsy guidance. To meet these demands, in addition to routine T1-weighted, T2-weighted, DCE-MRI, diffusion MRI, and MR spectroscopy, several new MR methods such as restriction spectrum imaging, vascular, extracellular, and restricted diffusion for cytometry in tumors (VERDICT) method, hybrid multi-dimensional MRI, luminal water imaging, and MR fingerprinting have been developed for a better characterization of the disease. Further, with the increasing interest in combining MR data with clinical and genomic data, there is a growing interest in utilizing radiomics and radiogenomics approaches. These big data can also be utilized in the development of computer-aided diagnostic tools, including automatic segmentation and the detection of clinically significant PCa using machine learning methods., (© 2022. The Author(s), under exclusive licence to European Society for Magnetic Resonance in Medicine and Biology (ESMRMB).)

In the present paper, the theoretical investigation of the device structure ITO/CeO 2 /SnS/Spiro-OMeTAD/Mo of SnS-based solar cell has been performed. The aim of this work is to examine how the Spiro-OMeTAD HTL affects the performance of SnS-based heterostructure solar cell. Using SCAPS-1D simulation software, various parameters of SnS-based solar cell such as work function, series and shunt resistance and working temperature have been investigated. With the help of Spiro-OMeTAD, the suggested cell's open-circuit voltage was increased to 344 mV. The use of Spiro-OMeTAD HTL in the SnS-based solar cell resulted in 14% efficiency increase, and the proposed heterojunction solar cell has 25.65% efficiency. The cell's performance is determined by the carrier density and width of the CeO 2 ETL (electron transport layer), SnS absorber layer and Spiro-OMeTAD HTL (hole transport layer). These data reveal that the Spiro-OMeTAD solar cells could have been a good HTL (hole transport layer) in regards to producing SnS-based heterojunction solar cell with high efficiency and reduced cost.

In the traditional surface plasmon resonance sensor, the sensitivity is calculated by the usage of angular interrogation. The proposed surface plasmon resonance (SPR) sensor uses a diamagnetic material (Al 2 O 3 ), nickel (Ni), and two-dimensional (2D) BlueP/WS 2 (blue phosphorous-tungsten di-sulfide). The Al 2 O 3 sheet is sandwiched between silver (Ag) and nickel (Ni) films in the Kretschmann configuration. A mathematical simulation is performed to improve the sensitivity of an SPR sensor in the visible region at a frequency of 633 nm. The simulation results show that an upgraded sensitivity of 332°/RIU is achieved for the metallic arrangement consisting of 17 nm of Al 2 O 3 and 4 nm of Ni in thickness for analyte refractive indices ranging from 1.330 to 1.335. The thickness variation of the layers plays a curial role in enhancing the performance of the SPR sensor. The thickness variation of the proposed configuration containing 20 nm of Al 2 O 3 and 1 nm of Ni with a monolayer of 2D material BlueP/WS 2 enhances the sensitivity to as high as 374°/RIU. Furthermore, it is found that the sensitivity can be altered and managed by means of altering the film portions of Ni and Al 2 O 3 .

An absolute or relative deficiency of pancreatic β-cells mass and functionality is a crucial pathological feature common to type 1 diabetes mellitus and type 2 diabetes mellitus. Glucagon-like-peptide-1 receptor (GLP1R) agonists have been the focus of considerable research attention for their ability to protect β-cell mass and augment insulin secretion with no risk of hypoglycemia. Presently commercially available GLP1R agonists are peptides that limit their use due to cost, stability, and mode of administration. To address this drawback, strategically designed distinct sets of small molecules were docked on GLP1R ectodomain and compared with previously known small molecule GLP1R agonists. One of the small molecule PK2 (6-((1-(4-nitrobenzyl)-1H-1,2,3-triazol-4-yl)methyl)-6H-indolo[2,3-b]quinoxaline) displays stable binding with GLP1R ectodomain and induces GLP1R internalization and increasing cAMP levels. PK2 also increases insulin secretion in the INS-1 cells. The oral administration of PK2 protects against diabetes induced by multiple low-dose streptozotocin administration by lowering high blood glucose levels. Similar to GLP1R peptidic agonists, treatment of PK2 induces β-cell replication and attenuate β-cell apoptosis in STZ-treated mice. Mechanistically, this protection was associated with decreased thioredoxin-interacting protein expression, a potent inducer of diabetic β-cell apoptosis and dysfunction. Together, this report describes a small molecule, PK2, as an orally active nonpeptidic GLP1R agonist that has efficacy to preserve or restore functional β-cell mass., Competing Interests: Conflict of interest No potential conflicts of interest relevant to this article were reported., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Chronic tissue injury resulting in fibrosis of multiple organs, responsible for one-third of the death globally. Liver fibrosis is a common pathway/condition involved in all chronic liver diseases. Thioacetamide (TAA), a hepatotoxicant, was used to induce hepatic fibrosis. Anti-diabetic drug glibenclamide (GLB) possesses anti-inflammatory properties and inhibits NACHT, LRR, and PYD domains-containing protein 3 (NLRP3) inflammasome activation. Dimethyl fumarate (DMF), a multiple sclerosis drug, activates the nuclear factor erythroid 2-related factor 2 (Nrf2)/antioxidant response element (ARE) pathway and maintains the antioxidant status in the cell. The present study was designed to investigate (i) role of NLRP3 inflammasome and Nrf2/ARE pathway in TAA-induced hepatotoxicity and liver fibrosis, (ii) mechanism involved in GLB and DMF mediated hepatoprotection against TAA-induced hepatotoxicity, and (iii) additional/synergistic hepatoprotective effect of combination treatment with NLRP3 inhibition + Nrf2 activation or GLB + DMF or MCC950 + 4OI to reverse/ameliorate the experimental liver fibrosis completely. TAA was administered intraperitoneally to mice for seven consecutive weeks, and treatments of GLB, DMF, GLB + DMF, MCC950, 4OI, and MCC950 + 4OI were provided for the last three consecutive weeks. The intervention with GLB, DMF, GLB + DMF, MCC950, 4OI, and MCC950 + 4OI significantly protected TAA-induced oxidative stress and inflammatory conditions by improving biochemical, histological, and immunoexpression changes in mice. The GLB, DMF, and GLB + DMF intervention exhibited a better protective effect compared with MCC950, 4OI, and MCC950 + 4OI, which revealed that this specific inhibitor/activator possesses only NLRP3 inflammasome inhibitory/Nrf2 activatory properties. In contrast, the clinical drug GLB and DMF have several other beneficial effects, which are independent of NLRP3 inhibition and Nrf2 activation., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The liver injury leads to an inflammatory response, which causes the activation of hepatic stellate cells (HSCs) that further secrete ECM proteins and play an important role in liver fibrosis. Moreover, the inflammatory response is a driving force for fibrogenesis, which is triggered by many types of injuries. Exaggerated inflammatory immune responses are mediated by cytoplasmic protein complexes known as inflammasomes, which are involved in many chronic liver diseases. Inflammasomes are pattern recognition receptors (PRRs) that can sense any microbial motifs known as pathogen-associated molecular patterns (PAMPs), and host- or environmental-derived stress signals known as damage-associated molecular patterns (DAMPs). The inflammasomes cause caspase-mediated proteolytic cleavage of pro-IL-1β and pro-IL-18 into active IL-1β and IL-18. In this review, we provide a comprehensive summary of the important roles of NLRP3 inflammasome in the pathogenesis of liver fibrosis with an emphasis on several direct and indirect pathways responsible for the NLRP3 inflammasome-mediated HSCs activation and fibrogenesis. In addition, we discuss the general pharmacological and genetics strategies for the inhibition of NLRP3 inflammasome activation and its downstream signaling with examples of emerging pharmacotherapeutics, targeting the NLRP3 inflammasome signaling as well as a possible way to develop effective and safer NLRP3 inflammasome inhibitors., (© 2022 The Authors. Publishing services by Elsevier B.V. on behalf of KeAi Communications Co., Ltd.)

A global challenge faced by light harvesting photocatalyst is how to promote the selective organic transformation, such as C-S bond formation via radical-radical coupling under solar light. Here, we report a two-dimensional covalent organic frameworks (2D-COFs), poly (perylene-imide-benzoquinone) nanorod through in situ condensation on flexible activated carbon cloth (PPIBNR-FACC) to function as a light harvester material for highly selective radical-radical coupling to vinyl sulfides (i.e. C-S bond activation). Such a structure supports charge transfer from PPIBNR to FACC, which is essential for the selective radical-radical coupling. Hence, organic transformation is attaining high yields and selectivity (˜99%) under solar light using in situ prepared PPIBNR-FACC photocatalyst. The structural virtues of PPIBNR-FACC will trigger the utmost investigations into designable and versatile 2D-COFs for fine chemical synthesis., (© 2021 American Society for Photobiology.)

Purpose: Intratumoral heterogeneity (ITH) challenges the molecular characterization of clear cell renal cell carcinoma (ccRCC) and is a confounding factor for therapy selection. Most approaches to evaluate ITH are limited by two-dimensional ex vivo tissue analyses. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) can noninvasively assess the spatial landscape of entire tumors in their natural milieu. To assess the potential of DCE-MRI, we developed a vertically integrated radiogenomics colocalization approach for multi-region tissue acquisition and analyses. We investigated the potential of spatial imaging features to predict molecular subtypes using histopathologic and transcriptome correlatives., Experimental Design: We report the results of a prospective study of 49 patients with ccRCC who underwent DCE-MRI prior to nephrectomy. Surgical specimens were sectioned to match the MRI acquisition plane. RNA sequencing data from multi-region tumor sampling (80 samples) were correlated with percent enhancement on DCE-MRI in spatially colocalized regions of the tumor. Independently, we evaluated clinical applicability of our findings in 19 patients with metastatic RCC (39 metastases) treated with first-line antiangiogenic drugs or checkpoint inhibitors., Results: DCE-MRI identified tumor features associated with angiogenesis and inflammation, which differed within and across tumors, and likely contribute to the efficacy of antiangiogenic drugs and immunotherapies. Our vertically integrated analyses show that angiogenesis and inflammation frequently coexist and spatially anti-correlate in the same tumor. Furthermore, MRI contrast enhancement identifies phenotypes with better response to antiangiogenic therapy among patients with metastatic RCC., Conclusions: These findings have important implications for decision models based on biopsy samples and highlight the potential of more comprehensive imaging-based approaches., (©2021 American Association for Cancer Research.)

Ethanol consumption increases the prevalence of gastric ulcer (GU) in rats with type II diabetes (T2D). Induction of GU by absolute ethanol (5 mL/kg or 3.94 g/kg) in the animal model resembles human ulcer characteristics. The aim was to investigate the role of the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway in the treatment of GU in diabetic condition. The rats were exposed to absolute ethanol 1 h before sacrifice and T2D was induced by combined exposure of high-fat diet and low dose streptozotocin. Pretreatment of tert -butylhydroquinone (tBHQ) (25 and 50 mg/kg), metformin (500 mg/kg), and omeprazole (20 mg/kg) were given once daily for last three consecutive weeks. In ethanol-exposed diabetic rats, pretreatment with tBHQ, omeprazole, and metformin reduced gastric mucosal lesion, ulcer index, histological alterations, malondialdehyde level, and apoptosis. Furthermore, the intervention of tBHQ, omeprazole, and metformin improved the integrity of the stomach mucosa, glutathione, gastric pH, collagen, and goblet cells. tBHQ treatment improved ethanol-induced alterations of Nrf2, catalase, heat shock protein 70 (HSP70), NF-κB, and endothelin-1 expressions in diabetic rats. In diabetic conditions, the incidence of GU is increased due to elevated levels of reactive oxygen species, inflammatory mediators, depleted levels of cellular antioxidants, and altered gastric parameters. The tBHQ intervention could be a rational strategy to protect these changes.

Introduction: Percutaneous renal mass biopsy results can accurately diagnose clear cell renal cell carcinoma (ccRCC); however, their reliability to determine nuclear grade in larger, heterogeneous tumors is limited. We assessed the ability of radiomics analyses of magnetic resonance imaging (MRI) to predict high-grade (HG) histology in ccRCC., Patients and Methods: Seventy patients with a renal mass underwent 3 T MRI before surgery between August 2012 and August 2017. Tumor length, first-order statistics, and Haralick texture features were calculated on T2-weighted and dynamic contrast-enhanced (DCE) MRI after manual tumor segmentation. After a variable clustering algorithm was applied, tumor length, washout, and all cluster features were evaluated univariably by receiver operating characteristic curves. Three logistic regression models were constructed to assess the predictability of HG ccRCC and then cross-validated., Results: At univariate analysis, area under the curve values of length, and DCE texture cluster 1 and cluster 3 for diagnosis of HG ccRCC were 0.7 (95% confidence interval [CI], 0.58-0.82, false discovery rate P = .008), 0.72 (95% CI, 0.59-0.84, false discovery rate P = .004), and 0.75 (95% CI, 0.63-0.87, false discovery rate P = .0009), respectively. At multivariable analysis, area under the curve for model 1 (tumor length only), model 2 (length + DCE clusters 3 and 4), and model 3 (DCE cluster 1 and 3) for diagnosis of HG ccRCC were 0.67 (95% CI, 0.54-0.79), 0.82 (95% CI, 0.71-0.92), and 0.81 (95% CI, 0.70-0.91), respectively., Conclusion: Radiomics analysis of MRI images was superior to tumor size for the prediction of HG histology in ccRCC in our cohort., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Urothelial carcinoma has become the ninth most common malignancy in the world. Since the 1980s, diverse studies and treatment methods came out with their possible effects along with certain limitations. Initially, platinum chemotherapy was considered as first-line treatment of the disease. Although it was proved to be effective initially, the most number of cases reported the reoccurrence of the disease. Furthermore, aberrant ligand- dependent and constitutive ligand-independent fibroblast growth factor receptor (FGFR) signaling has been reported in a large number of solid tumors, including urothelial carcinoma that became the basis for FGFR inhibition for the treatment of the disease. Erdafitinib is a pan-FGFR inhibitor that was recently approved in the USA for the treatment of locally advanced or metastatic FGFR3 or FGFR2 urothelial carcinoma. The drug is also being investigated as a treatment for other cancers, including cholangiocarcinoma, liver cancer, non-small cell lung cancer, prostate cancer, lymphoma cancer and oesophageal cancer. This article summarizes the various treatments that evolved for bladder cancer till now, a brief description of the biology of FGFR inhibition, clinical pharmacology, and various clinical trials of erdafitinib., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Aims and Objectives: To prospectively evaluate the impact of cardiopulmonary ultrasound (CPUS) on etiological diagnosis and treatment of critically ill acute respiratory failure (ARF) patients., Design: This is a prospective observational study conducted in a general intensive care unit (ICU) of a tertiary care center in India. Patients over 18 years old with presence of one of the objective criteria of ARF. Patients either consecutively admitted for ARF to ICU or already admitted to ICU for a different reason but later developed ARF during their hospital stay. Written informed consent in local language was obtained from next of kin., Interventions: All included patients underwent bedside CPUS including lung ultrasound (US) and transthoracic echocardiography plus targeted venous US by single investigator, blinded to clinical data. The US diagnosis of ARF etiology was shared with treating intensivist. Initial clinical diagnosis (ICD) and treatment plan (made before US) of each patient were compared with post-US clinical diagnosis and treatment plan. The changes in diagnosis and treatment up to 24 hours post-US were considered as impact of US., Results: Mean age of 108 included patients was 45.7 ± 20.4 years (standard deviation). The ICD was correct in 67.5% (73/108) cases, whereas the combined CPUS yielded correct etiological diagnosis in 88% (95/108) cases. Among the 108 included patients, etiological diagnosis of ARF was altered after CPUS in 40 (37%) patients, which included "diagnosis changed" in 18 (17%) and "diagnosis added" in 22 (20%). Treatment plan was changed in 39 (36%) patients after CPUS, which included surgical interventions in 17 (16%), changes in medical therapy in 12 (11%), and changes in ventilation strategy in 4 (3.5%) patients., Conclusion: This study demonstrates that use of combined US approach as an initial test in ARF, improves diagnostic accuracy for identification of underlying etiology, and frequently changes clinical diagnosis and/or treatment., How to Cite This Article: Barman B, Parihar A, Kohli N, Agarwal A, Dwivedi DK, Kumari G. Impact of Bedside Combined Cardiopulmonary Ultrasound on Etiological Diagnosis and Treatment of Acute Respiratory Failure in Critically Ill Patients. Indian J Crit Care Med 2020;24(11):1062-1070., Competing Interests: Source of support: Nil Conflict of interest: None, (Copyright © 2020; Jaypee Brothers Medical Publishers (P) Ltd.)

Zinc (Zn) plays an important role in maintaining the process of spermatogenesis and reproductive health. Bisphenol A (BPA), an endocrine disrupting chemical is known to be a reproductive toxicant in different animal models. The present study was designed to study the effect of two of the utmost determinative factors (Zn deficient condition and influence of toxicant BPA) on germ cell growth and overall male reproductive health in the testis, epididymis, and sperm using (a) biochemical, (b) antioxidant, (c) cellular damage, (d) apoptosis, and (e) protein expression measurements. Rats were divided into Control (normal feed and water), BPA (100 mg/kg/d), zinc deficient diet (ZDD; fed with ZDD), and BPA + ZDD for 8 weeks. Body and organ weights, sperm motility and counts, and sperm head morphology were evaluated. The histology of testes, epididymides, and prostate was investigated. Testicular deoxyribonucleic acid (DNA) damage was evaluated by Halo and Comet assay, apoptosis of sperm and testes were quantified by TUNEL assay. Serum protein electrophoretic patterns and testicular protein expressions such as Nrf-2, catalase, PCNA, and Keap1 were analyzed by Western blot analysis. The results showed that BPA significantly increased the testicular, epididymal, and prostrate toxicity in dietary Zn deficient condition due to testicular hypozincemia, hypogonadism, increased cellular and DNA damage, apoptosis, as well as perturbations in protein expression., (© 2020 Wiley Periodicals LLC.)

The absorption and binding energy of material plays an important role with a large surface area and conductivity for the development of any sensing device. The newly grown 2D nanomaterials like black phosphorus transition metal dichalcogenides (TMDCs) or graphene have excellent properties for sensing devices' fabrication. This paper summarizes the progress in the area of the 2D nanomaterial-based surface plasmon resonance (SPR) sensor during last decade. The paper also focuses on the structure of Kretschmann configuration, the sensing principle of SPR, its characteristic parameters, application in various fields, and some important recent works related to SPR sensors have also been discussed, based on the present and future scope of this field. The present paper provides a platform for researchers to work in the field of 2D nanomaterial-based SPR sensors.

The present study was designed to investigate the hepatoprotective potential of dimethyl fumarate (DMF) against thioacetamide (TAA)-induced liver damage. Wistar rats were treated with DMF (12.5, 25, and 50 mg/kg/day, orally) and TAA (200 mg/kg intraperitoneally, every third day) for 6 consecutive weeks. TAA exposure significantly reduced body weight, increased liver weight and index, and intervention with DMF did not ameliorate these parameters. DMF treatment significantly restored TAA-induced increase in the levels of aspartate aminotransferase, alanine aminotransferase, γ-glutamyl transferase, total bilirubin, uric acid, malondialdehyde, reduced glutathione, and histopathological findings such as inflammatory cell infiltration, deposition of collagen, necrosis, and bridging fibrosis. DMF treatment significantly ameliorated TAA-induced hepatic stellate cell activation, increase in inflammatory cascade markers (NACHT, LRR, and PYD domains-containing protein 3; NLRP3, apoptosis-associated speck like protein containing a caspase recruitment domain; ASC, caspase-1, nuclear factor-kappa B; NF-κB, interleukin-6), fibrogenic makers (α-smooth muscle actin; ɑ-SMA, transforming growth factor; TGF-β1, fibronectin, collagen 1) and antioxidant markers (nuclear factor (erythroid-derived 2)-like factor 2; Nrf2, superoxide dismutase-1; SOD-1, catalase). The present findings concluded that DMF protects against TAA-induced hepatic damage mediated through the downregulation of inflammatory cascades and upregulation of antioxidant status., (© 2020 Wiley Periodicals, Inc.)

Rationale: Alcoholism and obesity impart a deleterious impact on human health and affects the quality of life. Chronic consumption of alcohol and western diet has been reported to cause memory deficits. 7,8-dihydroxyflavone (7,8-DHF), a TrkB agonist, comprises antioxidant and anti-inflammatory properties in treating various neurological disorders., Objectives: The current study was aimed to determine the protective effect and molecular mechanism of 7,8-DHF against alcohol and high-fat diet (HFD)-induced memory deficits in rats., Methods: The adult male Wistar rats were given alcohol (3-15%) and HFD ad libitum for 12 weeks in different experimental groups. 7,8-DHF (5 mg/kg) was intraperitoneally injected daily for the last 4 weeks (9th-12th week)., Results: The alcohol and HFD administration caused cognitive impairment as evaluated through the Morris water maze (MWM) test in alcohol, HFD, and alcohol + HFD-fed animals. The last 4-week treatment of 7,8-DHF (5 mg/kg; i.p.) attenuated alcohol and HFD-induced memory loss. 7,8-DHF treatment also restored the glutathione (GSH) level along with attenuation of nitrite, malondialdehyde content (markers of oxidative and nitrosative stress), and reduction of the acetylcholinesterase activity in the hippocampus of alcohol and HFD-fed animals. Furthermore, the administration of 7,8-DHF caused downregulation of NF-κB, iNOS, and caspase-3 and upregulation of Nrf2, HO-1, and BDNF mRNA level in rat hippocampus., Conclusion: 7,8-DHF administration conferred beneficial effects against alcohol and HFD-induced memory deficit via its unique antioxidant, anti-inflammatory, anti-apoptotic potential, along with the activation of TrkB/BDNF signaling pathway in the hippocampus.

Taurine, an essential neutraceutical, has been reported to exhibit antioxidant and anti-inflammatory properties. Substantial evidence indicates that prolonged stress is one of the leading causes of psychological and physiological anomalies. Restraint stress (RS) rat model is the most widely used experimental model for the induction of chronic psycho-emotional stress. In the present study, Swiss albino male mice were restrained for 6 h/day for 28 consecutive days. Animals were divided into four groups: control, RS, RS + taurine, and taurine control group. Taurine, a potent antioxidant, was administered (200 mg/kg) orally along with RS for 28 days. The taurine intervention significantly restored the RS-induced neurobehavioral alterations evident by the elevated plus-maze, Morris water maze test, forced swim test, tail suspension test, and a sucrose preference test. Moreover, taurine significantly prevented hippocampal oxidative stress (lipid peroxidation, reduced glutathione, and nitrite) and other neurochemical (acetylcholinesterase, and IL-1β) anomalies. Using western blotting analyses, we demonstrate that taurine treatment significantly ameliorated the alterations in Brain-derived neurotrophic factor, caspase-3, and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) level in the hippocampus. Thus, Taurine effectively inhibited RS-induced oxidative stress, neuroinflammation, and apoptosis via a mechanism involving the inhibition of the NF-κB signaling pathway. In summary, our study is the first to demonstrate that NF-κB and caspase-3 inhibition, as well as BDNF augmentation, was involved in neuroprotective potential of taurine against RS-induced behavioural anomalies.

The prevalence of non-alcoholic fatty liver disease (NAFLD) is much higher in diabetic and obese individuals. Combined exposure of high-fat diet (HFD) and single low-dose streptozotocin (STZ) was used to induce type II diabetes-associated NAFLD, as it better replicates the human pathology of fatty liver. Glibenclamide (GLB) is a potent NLRP3 inflammasome inhibitor and possesses anti-inflammatory and anti-oxidant properties. So it was pertinent to investigate its hepatoprotective potential against NAFLD in rat. HFD was provided to rat for 17 consecutive weeks and glibenclamide (GLB; 0.5 and 2.5 mg/kg/day, orally) was administered for the last 12 consecutive weeks. Establishment of NAFLD was clearly indicated by significant increase in liver weight, glucose, triglyceride, cholesterol, % glycosylated haemoglobin and insulin levels, and GLB intervention reduced the same. GLB restored HFD-induced significant increase in ROS, MDA and decrease in GSH. Histopathological studies revealed the macro- and micro-vascular steatosis and mild degree of inflammation in HFD-fed rat compared with control, and GLB intervention reduced the same. HFD exposure significantly increased the DNA damage and apoptosis compared with control, and GLB intervention reduced the same. Immunohistochemical and immunoblotting findings showed that GLB improved the hepatic expressions of inflammatory markers (NLRP3, ASC, caspase-1, IL-1β, NF-κB), anti-oxidant markers (SOD, catalase) and insulin signalling markers (p-AKT, p-GSK-3β, p-IRS). Hepatoprotective effects of GLB was mediated by decreasing the levels of glucose, triglycerides, cholesterol, DNA damage, apoptosis and inflammatory markers, and by improving the anti-oxidant status and insulin signalling pathway in HFD fed rat.

Two-stage rat hepatocarcinogenesis model was used to induce early carcinogenesis in which thioacetamide (TAA) promotes diethylnitrosamine (DEN) initiated carcinogenesis. Dimethyl fumarate (DMF) used to treat multiple sclerosis, activates the nuclear factor erythroid 2-related factor 2 (Nrf2)/antioxidant responsive element (ARE) pathway during oxidative stress, and maintains antioxidant levels. Glibenclamide (GLB), a sulphonylurea drug used to treat type II diabetes, possesses anti-inflammatory properties and inhibits NLRP3 inflammasomes. The present study was designed to investigate the concurrent intervention of DMF and GLB on DEN + TAA-induced early hepatic carcinogenesis. DMF and GLB treatment improved DEN + TAA-induced decrease in body weight, increase in liver weight and plasma transaminases, histopathological alterations, DNA damage, and apoptosis. DMF and GLB intervention significantly ameliorated the DEN + TAA-induced alterations in the antioxidant (Nrf2, HO-1, SOD-1, catalase), inflammatory (NF-κB, NLRP3, ASC, caspase-1), fibrogenic (TGF-β1, collagen) and regenerative proliferative stress (GST-p, HGF, c-MET, TGFα, EGF, AFP) markers. The present results indicate that Nrf2/ARE activation and NLRP3 inhibition might be a rational approach to attenuate oxidative stress and chronic inflammation associated progression of hepatocarcinogenesis., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Fatty liver diseases are the most common and major health concern arises from the modern lifestyle and alcohol (ethanol) abuse. The prevalence of non-alcoholic fatty liver diseases (NAFLD) has been observed prominently in obese and diabetic individuals, while alcoholic liver disease is common in alcoholic persons. Fatty liver disease, such as steatohepatitis, leads to fibrosis, cirrhosis and eventually hepatocellular carcinoma. The present study was designed to investigate the effect of 7,8-Dihydroxyflavone (7,8-DHF) against high-fat diet (HFD) and ethanol (EtOH)-induced hepatotoxicity in rats., Methods: Male Wistar rats (150-200 g) were fed HFD (58% calories from fat) and EtOH (3-15% in drinking water) for 12 weeks. 7,8-DHF was administered intraperitoneally at the dose of 5 mg/kg/day for the last four weeks. After 12 weeks, biochemical, ELISA, RT-PCR, and histological studies have been carried out., Results: Biochemical analyses revealed the involvement of oxidative stress and inflammation in the liver of HFD and EtOH-fed rats. 7,8-DHF treatment significantly reduced HFD and EtOH-induced oxidative stress as evidenced by the reduction of lipid peroxidation and augmentation of reduced glutathione level. Moreover, IL-1β level was found significantly reduced in 7,8-DHF treated EtOH, HFD and EtOH+HFD groups. The semi-quantitative RT-PCR results indicated down-regulation of Nrf-2 and HO-1 and up-regulation of NF-κB and iNOS mRNA expression level in the liver of HFD and EtOH-fed rats, which was ameliorated by 7,8-DHF treatment., Conclusion: The present study suggested that 7,8-DHF could be an effective pharmacological intervention in combating HFD and EtOH-induced hepatotoxicity., (Copyright © 2019 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier B.V. All rights reserved.)