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Importance: Disease models for atopic dermatitis (AD) have primarily focused on understanding underlying environmental, immunologic, and genetic etiologies. However, the role of metabolic mechanisms in AD remains understudied. Objective: To investigate the circulating blood metabolomic and cytokine profile of AD as compared to healthy control patients. Design: This study collected plasma from 20 atopic dermatitis with moderate-to-severe itch (score of ≥5 on the itch Numeric Rating Scale and IGA score =3) and 24 healthy control patients. Mass-spectrometry based metabolite data were compared between AD and healthy controls. Unsupervised and supervised machine learning algorithms and univariate analysis analyzed metabolic concentrations. Metabolite enrichment and pathway analyses were performed on metabolites with significant fold change between AD and healthy control patients. To investigate the correlation between metabolites levels and cytokines, Spearman's rank correlation coefficients were calculated between metabolites and cytokines. Setting: Patients were recruited from the Johns Hopkins Itch Center and dermatology outpatient clinics in the Johns Hopkins Outpatient Center. Participants: The study included 20 atopic dermatitis patients and 24 healthy control patients. Main outcomes and measures: Fold changes of metabolites in AD vs healthy control plasma. Results: In patients with AD, amino acids isoleucine, tyrosine, threonine, tryptophan, valine, methionine, and phenylalanine, the amino acid derivatives creatinine, indole-3-acrylic acid, acetyl-L-carnitine, L-carnitine, 2-hydroxycinnamic acid, N-acetylaspartic acid, and the fatty amide oleamide had greater than 2-fold decrease (all P-values<0.0001) compared to healthy controls. Enriched metabolites were involved in branched-chain amino acid (valine, leucine, and isoleucine) degradation, catecholamine biosynthesis, thyroid hormone synthesis, threonine metabolism, and branched and long-chain fatty acid metabolism. Dysregulated metabolites in AD were positively correlated cytokines TARC and MCP-4 and negatively correlated with IL-1a and CCL20. Conclusions and relevance: Our study characterized novel dysregulated circulating plasma metabolites and metabolic pathways that may be involved in the pathogenesis of AD. These metabolic pathways serve as potential future biomarkers and therapeutic targets in the treatment of AD. [ABSTRACT FROM AUTHOR]

Purpose: Pyrus boissieriana is a rich source of arbutin and has been used in herbal medicine to treat infectious diseases. This study aimed to investigate the effect of the arbutin-rich fraction of Pyrus boissieriana aerial parts on Toxoplasma gondii In Vitro and In Vivo. Methods: An arbutin-rich fraction of P. boissieriana was prepared beforehand. Flow cytometry was used to evaluate the effect of different concentrations (1–512 µg/ml) of the P. boissieriana arbutin-rich fraction on Toxoplasma tachyzoites (RH strain). The cytotoxicity of the concentrations on the macrophage J774 cell line was also investigated by MTT assay. For In Vivo investigation, 4–6-week-old female mice infected with the RH strain of T. gondii were treated with different doses (16, 32, 64, 256, and 512 mg/kg) of the fraction using gavage. Results: The highest and lowest lethality of the tachyzoites were 89.6% and 25.9% related to the concentrations of 512 µg/ml and 1 µg/ml, respectively, with an IC50 value of 18.1 µg/ml ± 0.37. The cytotoxicity test showed an IC50 value of 984.3 µg/ml ± 0.76 after 48 h incubation. The mean survival of mice at the lowest treated dose (16 mg/kg) was 6.6 days, and it was 15 days at the highest dose (512 mg/kg). The concentrations of 512, 256, 128, and 64 mg/kg of the fraction compared to the negative control (6.2 days mean survival) significantly increased the survival time of mice (P < 0.001, P = 0.009, P = 0.018, and P = 0.021, respectively). Conclusion: The results showed that the arbutin-rich fraction of P. boissieriana is effective against T. gondii In Vitro and In Vivo and may be a reliable alternative to conventional treatment for toxoplasmosis, although further studies are necessary. [ABSTRACT FROM AUTHOR]

The discovery of neuroglobin (Ngb), a brain- or neuron-specific member of the hemoglobin family, has revolutionized our understanding of brain oxygen metabolism. Currently, how Ngb plays such a role remains far from clear. Here, we report a novel mechanism by which Ngb might facilitate neuronal oxygenation upon hypoxia or anemia. We found that Ngb was present in, co-localized to, and co-migrated with mitochondria in the cell body and neurites of neurons. Hypoxia induced a sudden and prominent migration of Ngb towards the cytoplasmic membrane (CM) or cell surface in living neurons, and this was accompanied by the mitochondria. In vivo, hypotonic and anemic hypoxia induced a reversible Ngb migration toward the CM in cerebral cortical neurons in rat brains but did not alter the expression level of Ngb or its cytoplasm/mitochondria ratio. Knock-down of Ngb by RNA interference significantly diminished respiratory succinate dehydrogenase (SDH) and ATPase activity in neuronal N2a cells. Over-expression of Ngb enhanced SDH activity in N2a cells upon hypoxia. Mutation of Ngb at its oxygen-binding site (His64) significantly increased SDH activity and reduced ATPase activity in N2a cells. Taken together, Ngb was physically and functionally linked to mitochondria. In response to an insufficient oxygen supply, Ngb migrated towards the source of oxygen to facilitate neuronal oxygenation. This novel mechanism of neuronal respiration provides new insights into the understanding and treatment of neurological diseases such as stroke and Alzheimer's disease and diseases that cause hypoxia in the brain such as anemia. [ABSTRACT FROM AUTHOR]

Hypoxia is characterized by low oxygen levels in the body or environment, resulting in various physiological and pathological changes. The brain, which has the highest oxygen consumption of any organ, is particularly susceptible to hypoxic injury. Exposure to low-pressure hypoxic environments can cause irreversible brain damage. Hypoxia can occur in healthy individuals at high altitudes or in pathological conditions such as trauma, stroke, inflammation, and autoimmune and neurodegenerative diseases, leading to severe brain damage and impairments in cognitive, learning, and memory functions. Exosomes may play a role in the mechanisms of hypoxic injury and adaptation and are a current focus of research. Investigating changes in exosomes in the central nervous system under hypoxic conditions may aid in preventing secondary damage caused by hypoxia. This paper provides a brief overview of central nervous system injury resulting from hypoxia, and aimed to conduct a comprehensive literature review to assess the pathophysio-logical impact of exosomes on the central nervous system under hypoxic conditions. [ABSTRACT FROM AUTHOR]

Background: Folk medicine is crucial to healthcare delivery in the underdeveloped countries. It is frequently used as a primary treatment option or as a complementary therapy for malaria. Malaria is a deadly disease which greatly threatens global public health, claiming incredible number of lives yearly. The study was aimed at documenting the medicinal plants used for malaria treatment in folk medicine in Kwara State, Nigeria. Methods: Ethnobotanical information was collected from selected consenting registered traditional medicine practitioners (TMPs) through oral face-to-face interviews using in-depth, semi-structured interview guide. The ethnobotanical data were analysed, and descriptive statistical methods were used to compile them. Results: Sixty-two indigenous medicinal plants, including 13 new plants, used for malaria treatment were identified in this study. The TMPs preferred decoction in aqueous solvent (34%) and steeping in decaffeinated soft drink (19%) for herbal preparations. Oral administration (74%) was the main route of administration, while leaves (40%) and stem barks (32%) were the most dominant plant parts used in herbal preparations. The most cited families were Fabaceae (15%) and Rutaceae (6%), while Mangifera indica (77.14%), Enantia chlorantha (65.71%), Alstonia boonei (57.14%) followed by Cymbopogon citratus (54.29%) were the most used plants. Besides, the antimalarial activities of many of the plants recorded and their isolated phytocompounds have been demonstrated. Furthermore, the conservation status of 4 identified plants were Vulnerable. Conclusion: The study showed strong ethnobotanical knowledge shared by the TMPs in the State and provides preliminary information that could be explored for the discovery of more potent antimalarial compounds. [ABSTRACT FROM AUTHOR]

Background: The era of nanotechnology become widespread for research and human resource development due to its functionalized tuning with economical, eco-friendly, effective and sustainable end-products. Hence, the present review illustrates the biogenic fabrication of platinum nanoparticles (PtNPs) through the different sustainable and cheaper approaches. Over the physicochemical-based nanotechnology, the biogenic active substances-based synthesis displayed the more promising candidature due to its non-toxic, Broad-spectrum applicability and defendable type character. The biogenic synthesis method is capable with and without capping and highly motif of reducing agents. The morphology and stability of synthesized PtNPs are mostly mediated by various experimental conditions such as pH, temperature, incubation time, concentrations of biomaterials and salts or enzymes used. Hence, the review is aiming to discuss the methodology of biogenic synthesis of PtNPs by plant stem, root, leaf, flower, fruit, extracts, algae, fungi and egg yolk. Also, we have illustrated the pharmaceutical drug model application and its adverse effect. Short conclusion: Synthesized PtNPs are open a new trend in catalyst, drug and its carrier and in cancer treatment. PtNPs are utilized as a new therapeutic agent for inhibiting the microbial pathogens with non-toxic behavior. The characterization of PtNPs could estimate the bio-sensitized properties which leads the commercial applications. [ABSTRACT FROM AUTHOR]

Due to the rise in bacterial resistance towards various therapeutic agents, interest is now developing towards fatty acid based antimicrobials because of their non-specific mode of action. A strain SORS 24 isolated from Sonchus oleraceus (Sow thistle) showed significant activity against Escherichia coli ATCC 25922 (25 mm), Chlorella vulgaris (20 mm), Bacillus subtilis DSM 10 (ATCC 6051) and Pseudomonas sp. (15 mm). It displayed an LC50 value of 10 µg/ml against Artemia salina (Brine shrimp) nauplii and an EC50 value of 0.8 µg/ml in the (DPPH) diphenylpicrylhydrazyl antioxidant assay. The strain also displayed genotoxicity against a PolA deficient strain, E. coli K-12 AB 3027 (15 mm). Mass spectrometry (HPLC-MS) showed that the strain produced oleamide (9-Octadecenamide) and erucamide (13-Docosenamide). Both of the purified fatty acid amides showed prominent activity against B. subtilis DSM 10 (ATCC 6051) (20 mm) and E. coli ATCC 25922 (15 mm). Significant genotoxicity was observed against E. coli K-12 AB 3027 (15 mm). The 16S gene sequencing revealed that the strain belonged to species, Streptomyces tanashiensis. As far as our understanding, this is the first report of this species producing these fatty acid based antimicrobials. [ABSTRACT FROM AUTHOR]

Pancreatic ductal adenocarcinoma (PDAC) is the most common exocrine tumor of the pancreas characterized by late diagnosis, adverse overall 5-year survival, a higher propensity for metastatic disease, and lack of efficacy of systemic therapy options. These adverse outcomes can be partly attributed to complex tumor microenvironment (TME). Over the past decade, immunotherapy has revolutionized the management of certain cancers; thus far, the immunologically 'non-inflamed' tumor microenvironment in PDACs has proven to be challenging. Indolamine 2,3-dioxygenase 1 (IDO1) is the rate-limiting enzyme in the catabolic pathway of LTryptophan, an essential amino acid, that gives rise to the immunosuppressive metabolite Kynurenine. IDO1, Indolamine 2,3-dioxygenase 2 (IDO2), and Tryptophan 2,3-dioxygenase (TDO) are the key enzymes in the tryptophan catabolic pathway but we focus on the role of the predominant enzyme form IDO1 in this review. Nicotinamide phosphoribosyl transferase (iNAMPT) regulates the intracellular concentration of NAD and is upregulated in the tumor. In light of the potential role of IDO1 as a driver of hostile TME in PDAC and NAD+ as a key coenzyme in anti-tumor immune response, this review urges focus on extensive research and initiation of clinical trials using IDO1 and NAMPT inhibitors in pancreatic cancer in the future. [ABSTRACT FROM AUTHOR]

Background: Reports have implicated diabetes mellitus (DM) and Alzheimer's disease (AD) as some of the global persistent health challenges with no lasting solutions, despite of significant inputs of modern-day pharmaceutical firms. This study therefore, aimed to appraise the in vitro antioxidant potential, enzymes inhibitory activities, and as well carry out in silico study on bioactive compounds from polyphenolic-rich extract of Hibiscus cannabinus seed (PEHc). Methods: In vitro antioxidant assays were performed on PEHc using standard methods while the identification of phytoconstituents was carried out with high performance liquid chromatography (HPLC). For the in silico molecular docking using Schrodinger's Grid-based ligand docking with energetics software, seven target proteins were retrieved from the database (https://www.rcsb.org/). Results: HPLC technique identified twelve chemical compounds in PEHc, while antioxidant quantification revealed higher total phenolic contents (243.5 ± 0.71 mg GAE/g) than total flavonoid contents (54.06 ± 0.09 mg QE/g) with a significant (p < 0.05) inhibition of ABTS (IC50 = 218.30 ± 0.87 µg/ml) and 1, 1-diphenyl-2-picrylhydrazyl free radicals (IC50 = 227.79 ± 0.74 µg/ml). In a similar manner, the extract demonstrated a significant (p < 0.05) inhibitory activity against α-amylase (IC50 = 256.88 ± 6.15 µg/ml) and α-glucosidase (IC50 = 183.19 ± 0.23 µg/ml) as well as acetylcholinesterase (IC50 = 262.95 ± 1.47 µg/ml) and butyrylcholinesterase (IC50 = 189.97 ± 0.82 µg/ml), respectively. Furthermore, In silico study showed that hibiscetin (a lead) revealed a very strong binding affinity energies for DPP-4, (PDB ID: 1RWQ) and α-amylase (PDB ID: 1SMD), gamma-tocopherol (for peptide-1 receptor; PDB ID: 3C59, AChE; PDB ID: 4EY7 and BChE; PDB ID: 7B04), cianidanol for α-glucosidase; PDB ID: 7KBJ and kaempferol for Poly [ADP-ribose] polymerase 1 (PARP-1); PDB ID: 6BHV, respectively. More so, ADMET scores revealed drug-like potentials of the lead compounds identified in PEHc. Conclusion: As a result, the findings of this study point to potential drug-able compounds in PEHc that could be useful for the management of DM and AD. [ABSTRACT FROM AUTHOR]

With the increasing of altitude activities from low-altitude people, the study of high altitude cerebral edema (HACE) has been revived. HACE is a severe acute mountain sickness associated with exposure to hypobaric hypoxia at high altitude, often characterized by disturbance of consciousness and ataxia. As for the pathogenesis of HACE, previous studies suggested that it might be related to the disorder of cerebral blood flow, the destruction of blood-brain barrier and the injury of brain parenchyma cells caused by inflammatory factors. In recent years, studies have confirmed that the imbalance of REDOX homeostasis is also involved in the pathogenesis of HACE, which mainly leads to abnormal activation of microglia and destruction of tight junction of vascular endothelial cells through the excessive production of mitochondrial-related reactive oxygen species. Therefore, this review summarizes the role of REDOX homeostasis and the potential of the treatment of REDOX homeostasis in HACE, which is of great significance to expand the understanding of the pathogenesis of HACE. Moreover, it will also be helpful to further study the possible therapy of HACE related to the key link of REDOX homeostasis. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) is a neurodegenerative disease characterized by the pathological loss of nigrostriatal dopaminergic neurons, which causes an insufficient release of dopamine (DA) and then induces motor and nonmotor symptoms. Hyperoside (HYP) is a lignan component with anti-inflammatory, antioxidant, and neuroprotective effects. In this study, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and its active neurotoxic metabolite 1-methyl-4-phenylpyridinium ion (MPP+) were used to induce dopaminergic neurodegeneration. The results showed that HYP (100 µg/mL) reduced MPTP-mediated cytotoxicity of SH-SY5Y cells in vitro, and HYP [25 mg/(kg d)] alleviated MPTP-induced motor symptoms in vivo. HYP treatment reduced the contents of nitric oxide (NO), H2O2, and malondialdehyde (MDA), as well as the mitochondrial damage of dopaminergic neurons, both in vitro and in vivo. Meanwhile, HYP treatment elevated the levels of neurotrophic factors such as glial cell line–derived neurotrophic factor, brain-derived neurotrophic factor, and recombinant cerebral dopamine neurotrophic factor in vivo, but not in vitro. Finally, Akt signaling was activated after the administration of HYP in MPP+/MPTP-induced dopaminergic neurodegeneration. However, the blockage of the Akt pathway with Akt inhibitor did not abolish the neuroprotective effect of HYP on DA neurons. These results showed that HYP protected the dopaminergic neurons from the MPP+- and MPTP-induced injuries, which did not rely on the Akt pathway. [ABSTRACT FROM AUTHOR]

Intervertebral disk degeneration (IDD) is a chronic inflammatory disease with intricate connections between immune infiltration and oxidative stress (OS). Complex cell niches exist in degenerative intervertebral disk (IVD) and interact with each other and regulate the disk homeostasis together. However, few studies have used longitudinal approach to describe the immune response of IDD progression. Here, we conducted conjoint analysis of bulk-RNA sequencing and single-cell sequencing, together with a series of techniques like weighted gene co-expression network analysis (WGCNA), immune infiltration analysis, and differential analysis, to systematically decipher the difference in OS-related functions of different cell populations within degenerative IVD tissues, and further depicted the longitudinal alterations of immune cells, especially monocytes/macrophages in the progression of IDD. The OS-related genes CYP1A1, MMP1, CCND1, and NQO1 are highly expressed and might be diagnostic biomarkers for the progression of IDD. Further landscape of IVD microenvironment showed distinct changes in cell proportions and characteristics at late degeneration compared to early degeneration of IDD. Monocytes/macrophages were classified into five distinct subpopulations with different roles. The trajectory lineage analysis revealed transcriptome alterations from effector monocytes/macrophages and regulatory macrophages to other subtypes during the evolution process and identified monocytes/macrophage subpopulations that had rapidly experienced the activation of inflammatory or anti-inflammatory responses. This study further proposed that personalized therapeutic strategies are needed to be formulated based on specific monocyte/macrophage subtypes and degenerative stages of IDD. [ABSTRACT FROM AUTHOR]

Background: Several results demonstrated that microglia and peripheral monocytes/macrophages infiltrating the central nervous system (CNS) are involved in cell response against toxic compounds. It has been shown that rotenone induces neurodegeneration in various in vitro experimental models. Baicalin, a natural compound, is able to attenuate cell damage through anti-oxidant, anti-microbial, anti-inflammatory, and immunomodulatory action. Using THP-1 monocytes, we investigated rotenone effects on mitochondrial dysfunction and apoptosis, as well as baicalin ability to counteract rotenone toxicity. Methods and results: THP-1 cells were exposed to rotenone (250 nM), in the presence/absence of baicalin (10–500 μM) for 2–24 h. Reactive Oxygen Species production (ROS), mitochondrial activity and transmembrane potential (Δψm), DNA damage, and caspase-3 activity were assessed. Moreover, gene expression of mitochondrial transcription factor a (mtTFA), interleukin-1β (IL-1β), B-cell lymphoma 2 (Bcl2) and BCL2-associated X protein (Bax), together with apoptotic morphological changes, were evaluated. After 2 h of rotenone incubation, increased ROS production and altered Δψm were observed, hours later resulting in DNA oxidative damage and apoptosis. Baicalin treatment at 50 µM counteracted rotenone toxicity by modulating the expression levels of some proteins involved in mitochondrial biogenesis and apoptosis. Interestingly, at higher baicalin concentrations, rotenone-induced alterations persisted. Conclusions: These results give evidence that exposure to rotenone may promote the activation of THP-1 monocytes contributing to enhanced neurodegeneration. In this context, baicalin at low concentration exerts beneficial effects on mitochondrial function, and thus may prevent the onset of neurotoxic processes. [ABSTRACT FROM AUTHOR]

This study emphasizes the production of eco-friendly silver nanoparticles from a medicinal plant extract of Morinda lucida (M. lucida) and investigated its antioxidant and antimicrobial activity. Phytochemical screening of M. lucida (ML) leave extract was carried out and observed to contain some fundamental phyto-reducing agents such as reducing sugar, proteins, and alkaloids. The green synthesized AgNPs (ML-AgNPs) were characterized by UV–vis spectroscopy, Fourier transform infrared spectroscopy (FTIR), transmission emission microscopy (TEM), scanning electron microscopy (SEM), X-ray diffraction (XRD), and Energy dispersive X-ray analysis (EDX). Thermo gravimetric analysis (TGA) was performed on the synthesized ML-capped AgNPs to determine the thermal stability and the formation of the green synthesized AgNPs. The formation of AgNPs was confirmed by the UV–vis absorption spectra, which showed an absorption band at 420 nm. The morphology of ML extract-mediated AgNPs was mostly spherical and rough-edged crystallite nanostructures, with an average particle size of 11 nm. The FTIR analyses revealed distinctive functional groups which were directly involved in the synthesis and stability of AgNPs. The crystallite size was 8.79 nm, with four intense peaks at 2θ angles of 38°, 44°, 64°, and 77°. At an energy level of 3.4 keV, a significant signal was observed indicating the production of thermally stable and pure crystallite AgNPs. The antioxidant property of green synthesized ML-AgNPs was determined to be 40% higher than that of crude M. lucida leaf extract. The ability of green synthesized ML-AgNPs to scavenge free radicals also increased in the order of OH− < NO < H2O2. The ML-AgNPs have strong activities with a maximum against P. vulgaris and a minimum with E. faecalis. [ABSTRACT FROM AUTHOR]

We would like to report the eco-friendly synthesis of reduced graphene oxide using aqueous extract of Acorus calamus (rhizome), dried fruit and seed parts of Terminalia bellirica, Helicteres isora and Quercus infectoria and the whole shell part of Turbinella pyrum by simple steam bath technique. The structural and morphological characteristics of prepared reduced graphene oxides were determined by UV–Visible spectroscopy, Fourier Transform Infra-Red spectroscopy (FTIR), Field Emission Scanning Electron Microscopy (FESEM) and Raman spectroscopy. The Surface Plasmon Resonance at 260–280 nm ensured the reduced graphene oxide formation. The antibacterial efficacy of synthesized reduced graphene oxide was evaluated against both gram-positive and gram-negative pathogens such as Staphylococcus aureus, Bacillus subtilis, Salmonella paratyphi and Escherichia coli. Among the selected samples Quercus infectoria mediated reduced graphene oxide showed excellent inhibition efficiency (27 and 28 mm) against Escherichia coli and Staphylococcus aureus, respectively as compared to the standard Gentamycin (29 mm). Quercus infectoria showed significant inhibition of 22 mm and moderate inhibition of 18 mm against Bacillus subtilis and Salmonella paratyphi, respectively. The results suggest selected plants and chank shell-mediated reduced graphene oxide as potential antibacterial agents for various therapeutic applications. [ABSTRACT FROM AUTHOR]

l-tryptophan, an essential amino acid, regulates protein homeostasis and plays a role in neurotransmitter-mediated physiological events. It also influences age-associated neurological alterations and neurodegenerative changes. The metabolism of tryptophan is carried majorly through the kynurenine route, leading to the production of several pharmacologically active enzymes, substrates, and metabolites. These metabolites and enzymes influence a variety of physiological and pathological outcomes of the majority of systems, including endocrine, haemopoietic, gastrointestinal, immunomodulatory, inflammatory, bioenergetic metabolism, and neuronal functions. An extensive literature review of PubMed, Medline, Bentham, Scopus, and EMBASE (Elsevier) databases was carried out to understand the nature of the extensive work done on the kynurenine metabolites that influence cellular redox potential, immunoregulatory mechanisms, inflammatory pathways, cell survival channels, and cellular communication in close association with several neurodegenerative changes. The imbalanced state of kynurenine pathways has found a close association to several pathological disorders, including HIV infections, cancer, autoimmune disorders, neurodegenerative and neurological disorders including Parkinson's disease, epilepsy and has found special attention in Alzheimer's disease (AD). Kynurenine pathway (KP) is intricately linked to AD pathogenesis owing to the influence of kynurenine metabolites on excitotoxic neurotransmission, oxidative stress, uptake of neurotransmitters, and modulation of neuroinflammation, amyloid aggregation, microtubule disruption, and their ability to induce a state of dysbiosis. Pharmacological modulation of KP pathways has shown encouraging results, indicating that it may be a viable and explorable target for the therapy of AD. [ABSTRACT FROM AUTHOR]

Gold nanoparticles (AuNPs) are increasingly being used in real clinical settings for drug delivery, gene transfer, cancer cell detection, phototherapy, and antiviral and anti-inflammatory activities, among other uses. Hence, knowledge about their potential toxicity and health impact is essential. This study therefore investigated the biochemical effects of gold nanoparticles in Wistar rats. Sixteen (16) Wistar rats were grouped into 4 (n = 4). Animals in the negative control group were orally administered 0.3 ml of distilled water (vehicle) while other treatment groups were respectively given oral administration of 0.3 ml each of 1, 10, and 20 mg/kg b.w. AuNPs for 7 days. Biochemical measurements of oxidative stress indices in rat plasma and tissue homogenates were recorded on a UV/Vis spectrophotometer. There was no significant (p > 0.05) difference in the plasma and brain for all the biochemical parameters measured, when compared with the negative control group. Conversely, AuNPs at 20 mg/kg b.w. significantly (p < 0.001) raised protein carbonyl and lipid peroxidation levels in the lungs and percentage (%) DNA fragmented levels in the liver (p < 0.05). These results indicate that AuNPs particularly at 20 mg/kg b.w. might predispose to oxidative stress. [ABSTRACT FROM AUTHOR]

Objective: Resveratrol (RSV) is a multitarget drug that has demonstrated activity against Toxoplasma gondii in macrophage and human foreskin fibroblast (HFF) cell line infection models. However, the mechanism of action of RSV has not yet been determined. Thus, with the aim of identifying a possible mechanism of the anti-T. gondii activity of this compound, we analyzed the effects of RSV on histones H3 and H4 lysine 16 acetylation (H4K16). We also analyzed RSV-induced DNA damage to intracellular tachyzoites by using the DNA damage marker phosphorylated histone H2A.X (γH2AX). Results: RSV inhibited intracellular T. gondii tachyzoite growth at concentrations below the toxic threshold for host cells. The IC50 value after 24 h of treatment was 53 μM. RSV induced a reduction in H4K16 acetylation (H4K16ac), a marker associated with transcription, DNA replication and homologous recombination repair. A similar deacetylation effect was observed on histone H3. RSV also increased T. gondii H2A.X phosphorylation at the SQE motif (termed γH2A.X), which is a DNA damage-associated posttranslational modification. Our findings suggest a possible link between RSV and DNA damage or repair processes that is possibly associated with DNA replication stress. [ABSTRACT FROM AUTHOR]

The problems of parasite resistance, as well as the toxic residues to most of the commercially available antipiroplasmic drugs severely weaken their effective, curative, and environmental safe employment. Therefore, it is clear that the development of treatment options for piroplasmosis is vital for improving disease treatment and control. Ciprofloxacin is a broad-spectrum antibiotic that targets mainly the DNA replication machinery by inhibiting DNA gyrase and topoisomerase enzymes. As a result, ciprofloxacin is used for treating several bacterial and parasitic infections. In this study, the efficacy of 15 novel ciprofloxacin derivatives (NCD) that had been developed against drug-resistant Mycobacterium tuberculosis was evaluated against piroplasm parasite multiplication in vitro. The half-maximal inhibitory concentration (IC50) values of the most effective five compounds of NCD (No. 3, 5, 10, 14, 15) on Babesia bovis, Babesia bigemina, Babesia caballi, and Theileria equi were 32.9, 13.7, 14.9, and 30.9; 14.9, 25.8, 13.6, and 27.5; 34.9, 33.9, 21.1, and 22.3; 26.7, 28.3, 34.5, and 29.1; and 4.7, 26.6, 33.9, and 29.1 μM, respectively. Possible detrimental effects of tested NCD on host cells were assessed using mouse embryonic fibroblast (NIH/3T3) and Madin-Darby bovine kidney (MDBK) cell lines. Tested NCD did not suppress NIH/3T3 and MDBK cell viability, even at the highest concentration used (500 μM). Combination treatments of the identified most effective compounds of NCD/diminazene aceturate (DA), /atovaquone (AQ), and /clofazimine (CF) showed mainly synergistic and additive effects. The IC50 values of NCD showed that they are promising future candidates against piroplasmosis. Further in vivo trials are required to evaluate the therapeutic potential of NCD. [ABSTRACT FROM AUTHOR]

Toxoplasmosis is a common parasitic disease caused by Toxoplasma gondii. Limitations of available treatments motivate the search for better therapies for toxoplasmosis. In this study, we synthesized a series of new imidazole derivatives: bis-imidazoles (compounds 1–8), phenyl-substituted 1H-imidazoles (compounds 9–19), and thiopene-imidazoles (compounds 20–26). All these compounds were assessed for in vitro potential to restrict the growth of T. gondii. To explore the structure–activity relationships, molecular analyses and bioactivity prediction studies were performed using a standard molecular model. The in vitro results, in combination with the predictive model, revealed that the imidazole derivatives have excellent selectivity activity against T. gondii versus the host cells. Of the 26 compounds screened, five imidazole derivatives (compounds 10, 11, 18, 20, and 21) shared a specific structural moiety and exhibited significantly high selectivity (> 1176 to > 27,666) towards the parasite versus the host cells. These imidazole derivatives are potential candidates for further studies. We show evidence that supports the antiparasitic action of the imidazole derivatives. The findings are promising in that they reinforce the prospects of imidazole derivatives as alternative and effective antiparasitic therapy as well as providing evidence for a probable biological mechanism. [ABSTRACT FROM AUTHOR]

Bacterial infections remain a serious health issue; hence there is a need for continuous search for improved anti-microbials. In addition, it is important to understand the antibacterial mechanism of prospective antimicrobials to fully harness their benefits. In this study, the antimicrobial action of silver nanoparticles was investigated. The antimicrobial potential of silver nanoparticles against different strains of bacteria was evaluated after which Escherichia coli and Staphylococcus aureus were selected as model for gram-negative and gram-positive bacteria respectively. Additionally, to determine mechanism of action, some biochemical assays including determination of kynurenine level, DNA fragmentation, lipid peroxidation and antioxidant status were carried out. Results showed that silver nanoparticles caused DNA damage and induced oxidative stress as reflected in elevated nitric oxide production and lipid peroxidation level. In contrast silver nanoparticles increased the antioxidant capacity viz-a-viz, elevated levels of total thiol, superoxide dismutase (SOD), and total antioxidant capacity (TAC) compared to untreated cells. They also initiated inconsistent alteration to the kynurenine pathway. Taken together, the findings indicate that silver nanoparticles exhibited antimicrobial action through the promotion of oxidative stress. [ABSTRACT FROM AUTHOR]

Background: There is a growing interest in the green synthesis of silver nanoparticles (AgNPs) using plant extract because the technique is cost effective, eco-friendly and environmentally benign. This is phasing out the use of toxic and hazardous chemical earlier reported. Tithonia diversifolia is a wild sunflower that grows widely in the western part of Nigeria with a proven medicinal benefit. However, several studies carried out have left doubts on the basic operational parameters needed for the green synthesis of AgNPs. The objective of this work was to carry out green synthesis of AgNPs using T. diversifolia extract via an eco-friendly route through optimization of various operational parameters, characterization, and antimicrobial studies. Method: Green synthesis of TD-AgNPs was done via bottom-up approach through wet chemistry technique using environmentally benign T. diversifolia plant extract as both reducing and stabilizing agent. Phytochemical Screening of the TD plant extract was carried out. Experimental optimization of various operational parameters--reaction time, concentration, volume ratio, and temperature was investigated. TD-AgNPs were characterized by UV-Vis spectroscopy, FTIR Spectroscopy, SEM/energy-dispersive X-ray spectroscopy (EDX), X-ray diffraction (XRD), and transmission electron microscopy (TEM). Antimicrobial studies against multi drug resistant microorganisms (MDRM) were studied using the agar well diffusion method. Results: This study reveals the importance of various operational parameters in the synthesis of TD-AgNPs. Excellent surface plasmon resonance peaks (SPR) were obtained at optimum experimental factors of 90 min reaction time under room temperature at 0.001 M concentration with the volume ratio of 1:9 (TD extract:Ag ion solution). The synthesis was monitored using UV-Vis and maximum wavelength obtained at 430 nm was due to SPR. The morphology and elemental constituents obtained by TEM, SEM, and EDX results revealed a spherical shape of AgNPs with prominent peak of Ag at 3.0 kV in EDX spectrum. The crystallinity nature was confirmed by XRD studies. FTIR analysis proved presence of biomolecules functioning as reducing, stabilizing, and capping agents. These biomolecules were confirmed to be flavonoid, triterpenes, and saponin from phytochemical screening. The antimicrobial studies of TD-AgNPs were tested against MDRM--Escherichia coli, Salmonella typhi, Salmonella enterica, and Bacillus subtilis. Discussion: The variation of reaction time, temperature, concentration, and volume ratio played substantive and fundamental roles in the synthesis of TD-AgNPs. A good dispersion of small spherical size between 10 and 26 nm was confirmed by TEM and SEM. A dual action mechanism of anti-microbial effects was provided by TD-AgNPs which are bactericidal and membrane-disruption. Based on the antimicrobial activity, the synthesized TD-AgNPs could find good application in medicine, pharmaceutical, biotechnology, and food science. [ABSTRACT FROM AUTHOR]

Citrullus vulgaris (watermelon) is a fruit with prophylactic and therapeutic potentials. In an attempt to maximize these potentials, the seed and rind are now often consumed together with the pulp. This study aimed at evaluating the implications of such consumption. Study involved the use of 35 Wistar rats grouped into seven with a control group administered distilled water, and the other groups administered varying concentrations of the pulp and whole fruit for 28 days. Alanine and aspartate aminotransferase (ALT, AST) were assayed in the serum and liver. Total protein of the serum and selected tissues was determined and malondialdehyde (MDA) level measured. Phytochemical screening revealed the presence of steroids, saponin, alkaloids, flavonoids, and terpenoids in both whole fruit and pulp. Significant increases ( p < 0.05) were seen in the liver ALT levels while there was a decreased ( p < 0.05) intestinal total protein in the treatment groups. No significant ( p ˃ 0.05) difference was seen in the serum and pancreas MDA levels while an increased ( p < 0.05) intestinal MDA level was observed. Increased liver ALT levels in all the treatment groups might be due to high glutamate levels of C. vulgaris. Decreased ( p ˂ 0.05) intestinal total protein might be indicative of protein loss, while elevated ( p < 0.05) intestinal MDA levels in the groups administered whole fruit is suggestive of a defect in absorption at the intestinal epithelium. Hence, whole fruit consumption of C. vulgaris should be done with caution as it has potential to cause intestinal oxidative stress. [ABSTRACT FROM AUTHOR]