The silver jubilee of the Nitric Oxide journal: From 1997 to 2021.

Based on the Scopus record, Nitric Oxide journal (NOJ) has completed 25 years of publications. On March 8, 2022, the publication data was retrieved from the Scopus database and analyzed on VOSviewer and R-Studio (Bibliometrix R package/Biblioshiny). NOJ has published 1928 research documents majorly comprising of articles (1611/83.56%) and reviews (210/10.89%). The total citations and h-index were 56291 & 97, respectively. The per year (from 1997 to 2022) publications and citations are presented in this study. We tried to highlight some of the influential researchers, institutes, and countries. In all publications, 7450 authors have contributed with a collaboration index of 0.241. For all authors, we provided descriptive details about their total number of publications (NoP), total citations (TC), h-index, g-index, m-index, citations per paper (CPP), citation per year (CPY), HG Sqrt and Q2Index. Based on each indicator, we highlighted the top five scientists. The research publications (over time) of the top ten authors are also described. Furthermore, the collaboration network of authors is graphically presented. We also provided descriptive details about the most productive institutes. The highest number of documents are published by the University of Sao Paolo (n = 78), Brazil, while in-country sections, USA has the highest number of publications (n = 553) with 21739 citations and 69 h-index. In the same vein, for each era (five years) details about the top five countries are provided. In all publications (n = 1794), 34 European, 3 North American, 13 Asian, 10 South American, 5 Middle East, 8 African and 2 Asia Pacific countries have contributed. Numerical details about the collaboration links of all countries and the per-era contributions of the top ten countries are also provided. Based on the co-words analysis the per era research focus is graphically presented. Descriptive details about the major trends in publication in each era are also provided. We also manually analyzed 160 words that appeared more than thirty thousand (n = 30,000) times and tried to provide a broader overview of research publications. Based on Scopus record, the NOJ ranking is yearly improving and presently (2021-2022) it holds 14th and 17th positions in clinical biochemistry and physiology. The success could be attributed to all researchers, institutes, editors-in-chief, reviewers, editorial board & entire management.

TGF-ß1 signaling can worsen NAFLD with liver fibrosis backdrop.

Non-Alcoholic Fatty Liver Disease (NAFLD) is characterized by the accumulation of fats in the liver. Relatively benign NAFLD often progresses to fibrosis, cirrhosis, and liver malignancies. Although NAFLD precedes fibrosis, continuous lipid overload keeps fueling fibrosis and the process of disease progression remains unhindered. It is well known that TGF-ß1 plays its part in liver fibrosis, yet its effects on liver lipid overload remain unknown. As TGF-ß1 signaling has been increasingly attempted to manage liver fibrosis, its actions on the primary suspect (NAFLD) are easily ignored. The complex interaction of inflammatory stress and lipid accumulation aided by mediators scuh as pro-inflammatory interleukins and TGF-ß1 forms the basis of NAFLD progression. Anticipatorily, the inhibition of TGF-ß1 signaling during anti-fibrotic treatment should reverse the NAFLD though the data remain scattered on this subject to date. TGF-ß1 signaling pathway is an important drug target in liver fibrosis and abundant literature is available on it, but its direct effects on NAFLD are rarely studied. This review aims to cover the pathogenesis of NAFLD focusing on the role of the TGF-ß1 in the disease progression, especially in the backdrop of liver fibrosis.

Molecular epidemiology and outcome of carbapenem-resistant Enterobacterales in Saudi Arabia.

BACKGROUND: The burden of carbapenem resistance is not well studied in the Middle East. We aimed to describe the molecular epidemiology and outcome of carbapenem-resistant Enterobacterales (CRE) infections from several Saudi Arabian Centers. METHODS: This is a multicenter prospective cohort study conducted over a 28-month period. Patients older than 14 years of age with a positive CRE Escherichia coli or Klebsiella pneumoniae culture and a clinically established infection were included in this study. Univariate and multivariable logistic models were constructed to assess the relationship between the outcome of 30-day all-cause mortality and possible continuous and categorical predictor variables. RESULTS: A total of 189 patients were included. The median patient age was 62.8 years and 54.0% were male. The most common CRE infections were nosocomial pneumonia (23.8%) and complicated urinary tract infection (23.8%) and 77 patients (40.7%) had CRE bacteremia. OXA-48 was the most prevalent gene (69.3%). While 100 patients (52.9%) had a clinical cure, 57 patients (30.2%) had died within 30 days and 23 patients (12.2%) relapsed. Univariate analysis to predict 30-day mortality revealed that the following variables are associated with mortality: older age, high Charlson comorbidity index, increased Pitt bacteremia score, nosocomial pneumonia, CRE bacteremia and diabetes mellitus. In multivariable analysis, CRE bacteremia remained as an independent predictor of 30 day all-cause mortality [AOR and 95% CI = 2.81(1.26-6.24), p = 0.01]. CONCLUSIONS: These data highlight the molecular epidemiology and outcomes of CRE infection in Saudi Arabia and will inform future studies to address preventive and management interventions.

Comprehensive characterization of Guanosine monophosphate synthetase in Nicotiana tabacum.

BACKGROUND: Guanosine monophosphate (GMP) synthetase is an enzyme that converts xanthosine monophosphate to GMP. GMP plays an essential role in plant development and responses to internal and external stimuli. It also plays a crucial role in several plant physiochemical processes, such as stomata closure, cation flux regulation, pathogen responses and chloroplast development. METHODS AND RESULTS: The mRNA sequences of NtGMP synthase in tobacco (Nicotiana tabacum) were rapidly amplified from cDNA. The GMP synthase open reading frame contains a 1617 bp sequence encoding 538 amino acids. A sequence analysis showed that this sequence shares high homology with that of Nicotiana sylvestris, Nicotiana attenuata, N. tomentosiformis, Solanum tuberosum, Lycopersicon pennellii, L. esculentum, Capsicum annuum, C. chinense and C. baccatum GMP synthase. A BLAST analysis with a tobacco high-throughput genomic sequence database revealed that the tobacco GMP synthase gene has five introns and six exons. A phylogenetic analysis showed a close genetic evolutionary relationship with N. sylvestris GMP synthase. The tissue-specific expression profile was evaluated using quantitative real-time PCR. The data showed that NtGMP synthase was highly expressed in leaves and moderately expressed in roots, flowers, and stems. The subcellular localization was predicted using the WOLF PSORT webserver, which strongly suggested that it might be localized to the cytoplasm. CONCLUSIONS: In the current study, we cloned and comprehensively characterized GMP synthase in tobacco (Nicotiana tabacum). Our results establish a basis for further research to explore the precise role of this enzyme in tobacco.

Efficiency of Soil Amendments for Copper Removal and Brassica Juncea (L.) Growth in Wastewater Irrigated Agricultural Soil.

Wastewater irrigation is becoming a massive challenge for sustainable agriculture. Particularly, copper (Cu) presence in wastewater poses a great threat to the food chain quality. Thus, scientists need to address this issue by using chemical and organic soil amendments to restore the soil ecosystem. Therefore, this study aims to examine the efficacy of sulphur, compost, acidified animal manure and sesame straw biochar for Cu immobilization, adsorption and Brassica growth in wastewater irrigated soil. The current findings presented that all the soil amendments prominently improved brassica yield and significantly minimized the Cu uptake by Brassica shoots and roots in sesame straw biochar (SB) (64.2% and 50.2%), compost (CP) (48% and 32.5%), acidified manure (AM) (37% and 23.2%) and Sulphur (SP) (16% and 3.1%) respectively relative to untreated soil. In addition, Cu bioavailability was reduced by 51%, 34%, 16.6%, and 7.4% when SB, CP, AM, and SP were incorporated in wastewater irrigated polluted soil. The Cu adsorption isotherm results also revealed that SB treated soil has great potential to increase Cu adsorption capacity by 223 mg g- 1 over control 89 mg g- 1. Among all the treatments, SB and CP were considered suitable candidates for the restoration of Cu polluted alkaline nature soil.

Disentangling climatic and anthropogenic contributions to nonlinear dynamics of alpine grassland productivity on the Qinghai-Tibetan Plateau.

Alpine grasslands on the Qinghai-Tibetan Plateau are sensitive and vulnerable to climate change and human activities. Climate warming and overgrazing have already caused degradation in a large fraction of alpine grasslands on this plateau. However, it remains unclear how human activities (mainly livestock grazing) regulates vegetation dynamics under climate change. Here, alpine grassland productivity (substituted with the normalized difference vegetation index, NDVI) is hypothesized to vary in a nonlinear trajectory to follow climate fluctuations and human disturbances. With generalized additive mixed modelling (GAMM) and residual-trend (RESTREND) analysis together, both magnitude and direction of climatic (in terms of temperature, precipitation, and radiation) and anthropogenic impacts on NDVI variation were examined across alpine meadows, steppes, and desert-steppes on the Qinghai-Tibetan Plateau. The results revealed that accelerating warming and greening, respectively, took place in 76.2% and 78.8% of alpine grasslands on the Qinghai-Tibetan Plateau. The relative importance of temperature, precipitation, and radiation impacts was comparable, between 20.4% and 24.8%, and combined to explain 66.2% of NDVI variance at the pixel scale. The human influence was strengthening and weakening, respectively, in 15.5% and 14.3% of grassland pixels, being slightly larger than any sole climatic variable across the entire plateau. Anthropogenic and climatic factors can be in opposite ways to affect alpine grasslands, even within the same grassland type, likely regulated by plant community assembly and species functional traits. Therefore, the underlying mechanisms of how plant functional diversity regulates nonlinear ecosystem response to climatic and anthropogenic stresses should be carefully explored in the future.

Abutilon indicum Exhibits Anxiolytic and Antidepressant Effects in Mice Models.

Abutilon indicum Linn (A. indicum) is native to tropical and subtropical zones and traditionally used in ulcer, diabetes, piles, jaundice, gonorrhoea and leprosy. Erstwhile phytochemical analysis showed the presence of flavonoids, sesquiterpenes, gallic acid, ß-sitosterols, geraniol, and caryophyllene. The study identifies the antidepressant potential of the crude methanolic extract of A. indicum (Ai.Cr). Crude methanolic extract of leaves and bark was prepared using maceration and freeze-drying. Forty Swiss-albino mice were divided into five groups containing eight mice each. Designated groups were administered with normal saline, Ai.Cr (30, 50, and 100 mg/kg) and diazepam (1 mg/kg) or fluoxetine (10 mg/kg) intra-peritoneally. Light and Dark Exploration (LDE), Elevated Plus Maze (EPM) and Hole Board (HB) test were used for anxiolytic activity testing, while forced swim and tail suspension model were used for the evaluation of antidepressant potential of Ai.Cr. Results showed that mice spent more time in light; passed more duration in open arms and raised number of head poking in respective anxiolytic LDE, EPM, and HB tests. Similarly, mobility time was raised in forced swim and tail suspension antidepressant testing. Ai.Cr has significant dose dependent antidepressant and anxiolytic potential, which peaks at highest dose (100 mg/kg) used in this study. A. indicum has significant pharmacological potential against anxiety and depression.

Another sleepless night: Does a leader's poor sleep lead to subordinate's poor sleep? A spillover/crossover perspective.

Given the importance of sleep to an individual's health and well-being, relatively little research has been conducted in the management and organizational behaviour literature on the relationship between sleep and work behaviour. Using spillover/crossover theory, we extended the current literature by investigating the possible supervisor-subordinate sleep relationship and introduced a serial mediation mechanism to answer how a supervisor's poor night's sleep translates into his/her subordinate's poor night's sleep. We conducted an experience sampling study involving 101 supervisors and subordinates over five consecutive working days (N = 505 occasions). Results verified that the spillover effect of supervisors' poor sleep on their next-day abusive supervisory behaviour has a crossover effect on their subordinates' poor sleep. Finally, results indicated that subordinate's physical exercise has the capacity to mitigate the influence of abusive supervision on subordinate' poor sleep. Future research should continue to examine the supervisor-subordinate sleep relationship and identify interventions in both the work and non-work domains of supervisor and subordinates as avenues for improving sleep health.

Berberis lycium Royle. extracts attenuate inflammation and modulates hyperglycemia in alloxan induced diabetic rats.

Berberis lycium Royle (Berberidaceae) is traditionally used for the treatment of diabetes mellitus. Present study was conducted to determine the antioxidant, antidiabetic and anti-inflammatory effects of aqueous and methanolic whole plant extracts. Total phenolic contents were determined by Folin-ciocalteu method whereas antioxidant activity was determined by 2,2-diphenyl-1-picryl hydrazyl (DPPH) method. In vitro anti-diabetic activity was determined using alpha amylase assay. Acute hypoglycemic activity was investigated on normoglycemic rats. Sub-acute anti-diabetic effects were investigated in alloxan induced diabetic rats for 14 days. Methanolic extract exhibited 183.5±1 mg/g Gallic acid equivalent (GAE) phenolic contents. The methanolic extract exhibited an IC50 of 242µg/mL and 37.26 mg/mL in antioxidant and alpha amylase inhibitory assays respectively. Administration of methanolic extract in normoglycemic rats exhibited significant anti-hyperglycemic effect at 90 and 120 min. Methanolic extract (500 mg/kg extract) significantly reduced blood glucose at day 14. Methanolic extract (500 mg/kg) significantly reduced the concentration of tumor necrosis factor (TNF-α) and interleukin (IL-6) along with reduction in total cholesterol and triglyceride levels in diabetic rats. Administration of methanol extract also improved the hepatic markers. The study suggested that the methanolic extract possessed antidiabetic effect that might be attributed to its alpha amylase, antioxidant and anti-inflammatory potential.

Immunometabolism features of metabolic deregulation and cancer.

Immunometabolism is a branch dealing at the interface of immune functionalities and metabolic regulations. Considered as a bidirectional trafficking, metabolic contents and their precursors bring a considerable change in immune cells signal transductions which as a result affect the metabolic organs and states as an implication. Lipid metabolic ingredients form a major chunk of daily diet and have a proven contribution in immune cells induction, which then undergo metabolic pathway shuffling inside their ownself. Lipid metabolic states activate relevant metabolic pathways inside immune cells that in turn prime appropriate responses to outside environment in various states including lipid metabolic disorders itself and cancers as an extension. Although data on Immunometabolism are still growing, but scientific community need to adjust and readjust according to recent data on given subject. This review attempts to provide current important data on Immunometabolism and consequently its metabolic ramifications. Incumbent data on various lipid metabolic deregulations like obesity, metabolic syndrome, obese asthma and atherosclerosis are analysed. Further, metabolic repercussions on cancers and its immune modalities are also analysed.

Ilex paraguariensis Attenuates Changes in Mortality, Behavioral and Biochemical Parameters Associated to Methyl Malonate or Malonate Exposure in Drosophila melanogaster.

Methylmalonic acidemia is a genetic disease characterized by accumulation of organic acids, such as methylmalonic (MMA) and malonic (MA) acids. Considering that the accumulation of MMA and MA causes several damages due to oxidative stress, antioxidants are thought to play a pivotal role in preventing deleterious effects associated with exposure to such compounds. Ilex paraguariensis (IP) was used here to test the hypothesis that supplementation with the aqueous extract of this plant could exert protective effect against MMA or MA induced mortality, behavioral and/or biochemical changes in Drosophila melanogaster (DM). Initially, a curve time- and dose-response to MMA (1-10 mM), MA (1-10 mM) and IP (63-500 µM) was performed. Thereafter, flies were concomitantly exposed to MA (5 mM), MMA (5 mM) and/or IP (250 µg/mL) during 15 days for survival assay, and for 48 hs to MA (1 or 5 mM), MMA (1 or 5 mM) and/or IP (250 µg/mL) for subsequent investigations. Both MMA and MA exposure resulted in higher incidence of mortality, a worse performance in the negative geotaxis assay and increased locomotion in open-field test as compared with control group. Furthermore, a marked increase in non-protein thiol (NPSH) and in thiobarbituric acid reactive substances (TBARS) levels, decrease in superoxide dismutase (SOD), catalase and acetylcholinesterase (AChE) activities, and decrease in MTT and resazurin reduction were noted in MMA or MA treated groups. IP treatment offered significant protection against all alterations associated to MMA or MA exposure. This study confirm the hypothesis that supplementation with IP offers protection against changes associated to MMA or MA exposure in DM, due, at least in part, to its antioxidant effect.

An assessment of bioavailability of acrylate based pH-sensitive complexes of lovastatin.

Lovastatin (LSN), a potent anti-hyperlipidemic drug, possesses poor bioavailability due to its very low aqueous solubility. The objective of this study was to establish a relationship between increased drug solubility before reaching site of absorption or increasing drug solubility at target absorption site for accentuated bioavailability of LSN. Composites of LSN with oppositely natured pH-sensitive acrylate polymers, cationic Eudragit EPO (EPO) and anionic Eudragit L100 (L100), were fabricated with physical trituration and kneading methods. Formulations were characterized for solubility, FTIR, PXRD, DSC, SEM, dissolution and bioavailability studies in rats. Interestingly, we observed that physical mixtures of EPO outmatched its kneaded formulations, whereas the physical mixtures and kneaded dispersions of L100 were virtually similar in characteristics. EPO was superior in boosting LSN solubility in the respective medium than the L100. Moreover, EPO produced immediate release profile in gastric environment whereas L100 offered sustained release of LSN in intestinal milieu. Bioavailability studies in rats further supported the EPO formulation in terms of shorter Tmax, higher Cmax and heightened AUC.

Interdependent and independent multidimensional role of tumor microenvironment on hepatocellular carcinoma.

The novelty of an effective therapeutic targeting for hepatocellular carcinoma (HCC) is based on improved understanding of each component of tumor microenvironment (TME) and its correspondent interactions at biological and molecular levels. In this context, new expansions for the treatment against TME and its communication with HCC are under exploration. Despite of the fact that blockage of growth factor receptors has become a treatment of choice in late phases of HCC in clinical practice, still a precise targeted treatment should address all the components of TME. Targeting one specific element out of cellular (cancer associated fibroblasts, endothelial cells, hepatic stellate cells, Kupffer cells and lymphocytes) or non-cellular (extracellular matrix, growth factors, inflammatory cytokines, proteolytic enzymes) parts of TME may not be a successful remedy for the disease because of well-designed hindrances of each component and their functional alternativeness. Meanwhile there are some elements of TME like epithelial-mesenchymal transition and CAF, which are considerably important and need thorough investigations. Ascertaining the potential role of these elements, and a single or combinational drug therapy targeting these elements of TME simultaneously, may provide the appreciable considerations to eventually improve in clinical practices and may also minimize the chances of reoccurrence of HCC.

Treatment with pentylenetetrazole (PTZ) and 4-aminopyridine (4-AP) differently affects survival, locomotor activity, and biochemical markers in Drosophila melanogaster.

PTZ is a convulsive agent that acts via selective blockage of GABAA receptor channels, whereas 4-AP leads to a convulsive episode via blockage of K+ channels. However, the mechanism(s) by which pentylenetetrazole (PTZ) and 4-aminopyridine (4-AP) cause toxicity to Drosophila melanogaster needs to be properly explored, once it will help in establishing an alternative model for development of proper therapeutic strategies and also to counteract the changes associated with exposure to both epileptic drugs. For the purpose, we investigated the effects of exposure (48 h) to PTZ (60 mM) and/or 4-AP (20 mM) on survival, locomotor performance, and biochemical markers in the body and/or head of flies. 4-AP-fed flies presented a higher incidence of mortality and a worse performance in the open field test as compared to non-treated flies. 4-AP also caused a significant increase in the reactive species (RS) and protein carbonyl (PC) content in the body and head. Also a significant increase in catalase and acetylcholinesterase (AChE) activities was observed in the body. In the same vein, PTZ exposure resulted in a significant increase in RS, thiobarbituric acid reactive substances (TBARS), PC content, and catalase activity in the body. PTZ exposure also caused a significant increase in AChE activity both in body and head. It is important to note that PTZ-treated flies also down-regulated the NRF2 expression. Moreover, both 4AP- and PTZ-fed flies presented a significant decrease in MTT reduction, down-regulation, and inhibition of SOD in body. However, SOD was significantly more active in the head of both 4-AP and PTZ-treated flies. Our findings provide evidence regarding the toxicological potential of both PTZ and/or 4-AP to flies. This model will help in decoding the underlying toxicological mechanisms of the stated drugs. It will also help to properly investigate the therapeutic strategies and to counteract the drastic changes associated with both epileptogenic drugs.

Peripheral-blood gene expression profiling studies for coronary artery disease and its severity in Xinjiang population in China.

BACKGROUND: Alterations in gene expression in peripheral blood cells play a curtail role in the presence and extent of coronary artery disease (CAD), but its severity reflected by gene expression alterations in peripheral blood cells is still unknown in Xinjiang population in China. METHODS: Global gene expression profiling in peripheral blood was used to explore differentially expressed genes in coronary artery stenosis patients. RNA was extracted from peripheral blood of 9 controls without coronary stenosis and 21 cases with angiographically CAD. The extent of CAD severity was categorized angiographically as no CAD, mild CAD (20 to 50% luminal diameter stenosis [LDS]), moderate CAD (50 to 75% LDS) and severe CAD (≥75% LDS). Differentially expressed genes related with CAD severity from peripheral blood cells were screened by linear mixed effects analysis using the lme4 package in R. Then the differentially expressed genes that gradually up-regulated or down-regulated were enriched by Gene Ontology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. RESULTS: The most significantly enrichments were toll-like receptor signaling pathway, immune responses, translational processes, cellular growth, inflammation and metabolic processes. Combined with NCBI-GeneRIF and PubMed analysis, we focused on the 12 genes associated with toll-like receptor signaling pathway in the extent of coronary artery stenosis patients. Receiver operating characteristic (ROC) analysis of 12 genes associated with toll-receptor signaling pathway in the 236 CAD patients from GEO database demonstrated that 12 genes expression could predict severe CAD with an area under the curve of 0.67, sensitivity of 77.65% and specificity of 51.52%. CONCLUSION: These results suggest that 12 genes associated with toll-like receptor signaling pathway in peripheral-blood cells reflect the presence and extent of CAD severity in Xinjiang population in China.

Water management regimes alter Pb uptake and translocation in fragrant rice.

Rice cultivation in lead (Pb) polluted soils often leads to high Pb contents in rice grains. The present study investigated the dynamics of Pb uptake under different water regimes in two fragrant rice cultivars i.e., Guixiangzhan and Nongxiang-18. Results revealed that water dynamics regulated the antioxidant activities in both rice cultivars under Pb toxicity. Compared to continuous ponding (CP), taken as control, alternate wetting and drying (AWD) reduced the Pb contents in roots, stems, leaves, and grains up to 17%, 41%, 22%, and 52% in Guixiangzhan and 23%, 19%, 17%, and 37% in Nongxiang-18, respectively. Furthermore, AWD-treatments reduced paddy yield from 11% to 21% in Guixiangzhan and 11-33% in Nongxiang-18 under Pb toxicity. In conclusion, Pb loadings in fragrant rice can be regulated by effective water management and/or by controlling irrigation water at different growth stages. Special control measures or management is required to cultivate the rice in metal(loid)s polluted soils.

Isoquercetin Improves Hepatic Lipid Accumulation by Activating AMPK Pathway and Suppressing TGF-ß Signaling on an HFD-Induced Nonalcoholic Fatty Liver Disease Rat Model.

Isoquercetin (IQ), a glucoside derivative of quercetin, has been reported to have beneficial effects in nonalcoholic fatty liver disease (NAFLD). In this study, we investigated the potential improvement of IQ in liver lipid accumulation, inflammation, oxidative condition, and activation in Kupffer cells (KCs) on a high-fat diet (HFD) induced NAFLD models. Male Sprague-Dawley (SD) rats were induced by HFD, lipopolysaccharides/free fatty acids (LPS/FFA) induced co-culture cells model between primary hepatocytes and Kupffer cells was used to test the effects and the underlying mechanism of IQ. Molecular docking was performed to predict the potential target of IQ. Significant effects of IQ were found on reduced lipid accumulation, inflammation, and oxidative stress. In addition, AMP-activated protein kinase (AMPK) pathway was activated by IQ, and is plays an important role in lipid regulation. Meanwhile, IQ reversed the increase of activated KCs which caused by lipid overload, and also suppression of Transforming growth factor beta (TGF-ß) signaling by TGF-ß Recptor-1 and SMAD2/3 signaling. Finally, TGF-ßR1 and TGF-ßR2 were both found may involve in the mechanism of IQ. IQ can improve hepatic lipid accumulation and decrease inflammation and oxidative stress by its activating AMPK pathway and suppressing TGF-ß signaling to alleviate NAFLD.