Effect of lycopene on TiO2 nanoforms induced oxidative stress and neuroinflammation in SH-SY5Y cells: an in vitro study.

Due to its antioxidant action, the carotenoid lycopene has been demonstrated to have a protective effect in several disease models; however, its effect on the nanoform of titanium oxide (nano-TiO2)-induced neurotoxicity has not yet been determined. The purpose of this study was to evaluate how lycopene affects neuronal damage brought on by nano-TiO2 and the mechanisms involved. SH-SY5Y cells were treated with different concentrations of nano-TiO2 for 48 hours, the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) test was used after that to evaluate cell viability. IC50 of nano-TiO2 was determined and the results revealed that IC50 is equal 40 µM/mL, lycopene (10 µM) was applied to SH-SY5Y human neuroblastoma cells an hour before exposure to 40 µM nano-TiO2. Reactive oxygen species, lipid peroxidation, nitric oxide, glutathione, superoxide dismutase, and catalase, tumor necrosis factor-alpha, interleukin 1 beta, nuclear factor kappa B, and apoptotic markers (Bcl2, Bax, and caspase-3), were measured to determine the anti-oxidant effect of lycopene. In SH-SY5Y neuroblastoma cells, pretreatment with 10 µM lycopene significantly reduced the toxicity brought on by exposure to nano-TiO2, according to MTT assay findings and lactate dehydrogenase (LDH) cytotoxicity assessment. In cells exposed to nano-TiO2, lycopene pretreatment significantly boosted the activity of antioxidative enzymes and reduced oxidative stress. Furthermore, when SH-SY5Y cells were subjected to nano-TiO2, lycopene pretreatment stopped neuroinflammation and apoptosis. The findings of this study suggest that lycopene may be an effective neuroprotective against oxidative stress and neuroinflammation and may be used to stop neuronal death or injury in a variety of neurological illnesses.

Proanthocyanidins alleviate pentylenetetrazole-induced epileptic seizures in mice via the antioxidant activity.

The role of oxidative stress in the initiation and progress of epilepsy is well established. Proanthocyanidins (PACs), a naturally occurring polyphenolic compound, have been reported to possess a broad spectrum of pharmacological and therapeutic properties against oxidative stress. However, the protective effects of proanthocyanidins against epilepsy have not been clarified. In the present study, we used the pentylenetetrazole (PTZ)-induced epilepsy mouse model to explore whether proanthocyanidins could help to reduce oxidative stress and protect against epilepsy. Mice were allocated into four groups (n = 14 per each group): control, PTZ (60 mg/kg, intraperitoneally), PACs + PTZ (200 mg/kg, p.o.) and sodium valproate (VPA) + PTZ (200 mg/kg, p.o.). PTZ injection caused oxidative stress in the hippocampal tissue as represented by the elevated lipid peroxidation and NO synthesis and increased expression of iNOS. Furthermore, depleted levels of anti-oxidants, GSH, GR, GPx, SOD, and CAT also indicate that oxidative stress was induced in mice exposed to PTZ. Additionally, a state of neuroinflammation was recorded following the developed seizures. Moreover, neuronal apoptosis was recorded following the development of epileptic convulsions as confirmed by the elevated Bax and caspase-3 and the decreased Bcl2 protein. Moreover, AChE activity, DA, NE, 5-HT, brain-derived neurotrophic factor levels, and gene expression of Nrf2 have decreased in the hippocampal tissue of PTZ exposed mice. However, pre-treatment of mice with PACs protected against the generation of oxidative stress, apoptosis, and neuroinflammation in the PTZ exposed mice brain as the biomarkers for all these conditions was bought to control levels. In addition, the gene expression of Nrf2 was significantly upregulated following PACs treatment. These results suggest that PACs can ameliorate oxidative stress, neuroinflammation, and neuronal apoptosis by activating the Nrf2 signaling pathway in PTZ induced seizures in mice.

Ameliorative effect of Spirulina and Saccharomyces cerevisiae against fipronil toxicity in Oreochromis niloticus.

The ameliorative effects of Spirulina and Saccharomyces cerevisiae (S. cerevisiae) against fipronil toxicity in Nile tilapia fish were investigated. Fipronil is a kind of pesticide that is widely used in agriculture, thus this trial was conducted to evaluate the effect of fipronil on growth related parameters (final body weight, feed intake, weight gain, feed conversion ratio, specific growth rate, and protein efficiency ratio), hematology related parameters (RBCs, WBCs, hemoglobin, packed cell volume, and deferential leukocytic count), biochemistry related parameters (alanine aminotransferase, aspartate aminotransferase, total protein, albumin, urea, and creatinine), histopathology of liver, intestine, gills, and spleen, and gene expression of antioxidants, stress, inflammatory, apoptotic, and related to junction proteins genes as SOD and GPx, COX II, TNF-α, Casp-3, and Claudin-3, respectively, in Nile tilapia (Oreochromis niloticus). Four hundred and five Nile tilapia fish were distributed in a glass aquarium into nine groups according to the Spirulina and S. cerevisiae supplemented diets, with or without fipronil contaminated water. The classified groups are control, Sc: S. cerevisiae (4 g/Kg diet), Sp: Spirulina (1 g/100 g diet), Fb1: 0.0021 mg fipronil/L, ScFb1: S. cerevisiae (4 g/Kg diet) with 0.0021 mg fipronil/L, SpFb1: Spirulina (1 g/100 g diet) with 0.0021 mg fipronil/L, Fb2: 0.0042 mg fipronil/L, ScFb2: S. cerevisiae (4 g/Kg diet) with 0.0042 mg fipronil/L, and SpFb2: Spirulina (1 g/100 g diet) with 0.0042 mg fipronil/L. The results of the present investigation indicated the negative effect of fipronil on the growth performance parameters of Nile tilapia, which was confirmed by the results of hematology, biochemistry, and histopathology. In addition, the results of gene expression of antioxidants, stress, inflammatory, and apoptotic genes indicate the genotoxicity of fipronil. However, these negative effects were ameliorated by Spirulina and Saccharomyces dietary supplementation.

Anticonvulsive Effects of Chondroitin Sulfate on Pilocarpine and Pentylenetetrazole Induced Epileptogenesis in Mice.

Chondroitin sulfate is a proteoglycan component of the extracellular matrix (ECM) that supports neuronal and non-neuronal cell activity, provides a negative domain to the extracellular matrix, regulates the intracellular positive ion concentration, and maintains the hypersynchronous epileptiform activity. Therefore, the present study hypothesized an antiepileptic potential of chondroitin sulfate (CS) in pentylenetetrazole-induced kindled epilepsy and pilocarpine-induced status epilepticus in mice. Levels of various oxidative stress markers and inflammatory mediators were estimated in the brain tissue homogenate of mice, and histopathological changes were evaluated. Treatment with valproate (110 mg/kg; i.p.) as a standard drug and chondroitin sulfate (100 & 200 mg/kg, p.o.) significantly (p < 0.01) and dose-dependently prevented the severity of kindled and spontaneous recurrent seizures in mice. Additionally, chondroitin sulfate showed its antioxidant potential by restoring the various biochemical levels and anti-inflammatory properties by reducing NF-kB levels and pro-inflammatory mediators like TNF-alpha, IL-1ß, and IL-6, indicating the neuroprotective effect as well as the suppressed levels of caspase-3, which indicated a neuroprotective treatment strategy in epilepsy. The proteoglycan chondroitin sulfate restores the normal physiology and configuration of the neuronal tissue. Further, the molecular docking of chondroitin sulfate at the active pockets of TNF-alpha, IL-1ß, and IL-6 showed excellent interactions with critical amino acid residues. In conclusion, the present work provides preclinical evidence of chondroitin sulfate as a new therapeutic approach in attenuating and preventing seizures with a better understanding of the mechanism of alteration in ECM changes influencing abnormal neuronal activities.

GC-MS Analysis and Biomedical Therapy of Oil from n-Hexane Fraction of Scutellaria edelbergii Rech. f.: In Vitro, In Vivo, and In Silico Approach.

The current study aimed to explore the crude oils obtained from the n-hexane fraction of Scutellaria edelbergii and further analyzed, for the first time, for their chemical composition, in vitro antibacterial, antifungal, antioxidant, antidiabetic, and in vivo anti-inflammatory, and analgesic activities. For the phytochemical composition, the oils proceeded to gas chromatography-mass spectrometry (GC-MS) analysis and from the resultant chromatogram, 42 bioactive constituents were identified. Among them, the major components were linoleic acid ethyl ester (19.67%) followed by ethyl oleate (18.45%), linolenic acid methyl ester (11.67%), and palmitic acid ethyl ester (11.01%). Tetrazolium 96-well plate MTT assay and agar-well diffusion methods were used to evaluate the isolated oil for its minimum inhibitory concentrations (MIC), minimum bactericidal concentration (MBC), half-maximal inhibitory concentrations (IC50), and zone of inhibitions that could determine the potential antimicrobial efficacy's. Substantial antibacterial activities were observed against the clinical isolates comprising of three Gram-negative bacteria, viz., Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa, and one Gram-positive bacterial strain, Enterococcus faecalis. The oils were also effective against Candida albicans and Fusarium oxysporum when evaluated for their antifungal potential. Moreover, significant antioxidant potential with IC50 values of 136.4 and 161.5 µg/mL for extracted oil was evaluated through DPPH (1,1-Diphenyl-2-picryl-hydrazyl) and ABTS assays compared with standard ascorbic acid where the IC50 values were 44.49 and 67.78 µg/mL, respectively, against the tested free radicals. The oils was also potent, inhibiting the α-glucosidase (IC50 5.45 ± 0.42 µg/mL) enzyme compared to the standard. Anti-glucosidase potential was visualized through molecular docking simulations where ten compounds of the oil were found to be the leading inhibitors of the selected enzyme based on interactions, binding energy, and binding affinity. The oil was found to be an effective anti-inflammatory (61%) agent compared with diclofenac sodium (70.92%) via the carrageenan-induced assay. An appreciable (48.28%) analgesic activity in correlation with the standard aspirin was observed through the acetic acid-induced writhing bioassay. The oil from the n-hexane fraction of S. edelbergii contained valuable bioactive constituents that can act as in vitro biological and in vivo pharmacological agents. However, further studies are needed to uncover individual responsible compounds of the observed biological potentials which would be helpful in devising novel drugs.

Lumpy skin disease in cattle in Sharkia, Egypt: epidemiological and genetic characterization of the virus.

Lumpy skin disease virus (LSDV) continues to threaten the cattle industry in Egypt. This survey investigated the epidemiological risk factors and the genetic characterization of circulating strains by partial sequencing of the P32 gene on cattle farms in the Sharkia Governorate, Egypt. Out of 600 cattle examined, morbidity, mortality, and case fatality were 31.2%, 1.8%, and 5.9%, respectively. Risk of LSD was higher among unvaccinated cattle kept outdoors compared to vaccinated cattle kept indoors, and the prevalence rates were statistically significantly different (P < 0.05). Regarding seasonal distribution, the highest number of cases was in June and July, and the lowest was in November. The P32 gene sequences showed that two LSDV isolates were 100% identical and 99.26% identical with 2017 Russian LSDV. Phylogenetic analysis revealed that two local isolates in this study were grouped together with other LSDVs from Russia (Saratov), Kenya, Greece, and Israel. The sequences in the study and other Egyptian sequences were grouped into two clusters with low genetic divergence, indicating that different strains are spreading in Egypt and that LSDV is more genetically related to sheep poxviruses than goat poxviruses. Our study confirms the necessity of evaluating the vaccination strategy adopted in Egypt, and sequence analysis based on the P32 gene is appropriate for genetic epidemiological studies of the local LSDVs.

Tocilizumab potentiates cisplatin cytotoxicity and targets cancer stem cells in triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is a very aggressive subtype with high recurrence rate and no molecular targets for therapies. This subtype is characterized by high expression/secretion of the proinvasive/metastatic interleukin-6 (IL-6) cytokine. In the present study, we have shown that tocilizumab inhibits the IL-6/STAT3 signaling and suppresses the cancer/inflammatory epigenetic IL-6/STAT3/NF-κB positive feedback loop. Furthermore, tocilizumab inhibited the proliferative and the migratory/invasiveness capacities as well as the epithelial-to-mesenchymal transition (EMT) process in TNBC cells. Importantly, tocilizumab suppressed the stemness-related characteristics of TNBC cells, through the inhibition of the Wnt/ß-catenin breast cancer stem cell-related pathway. Additionally, we have shown that tocilizumab suppresses the paracrine activation of normal breast stromal fibroblasts to myofibroblats. Moreover, tocilizumab sensitized TNBC cells to the cytotoxic effect of cisplatin in vitro. Furthermore, pharmacological inhibition of IL-6 by tocilizumab had great inhibitory effect on tumor growth and the EMT process in humanized orthotopic breast tumors in mice. In addition, tocilizumab potentiated the proapoptotic effect of cisplatin in humanized breast tumors. Together, these findings indicate that tocilizumab can suppress the prometastatic capacity of TNBC cells and enhances the cytotoxic effect of cisplatin against these cells. Therefore, tocilizumab could be of great therapeutic value for these hard-to-treat TNBC patients.

Oleuropein protects against lipopolysaccharide-induced sepsis and alleviates inflammatory responses in mice.

Sepsis results from a major systemic inflammatory response and can induce disorders in multiple organs. The present study evaluated the potential protective effects of oleuropein (OLE) against hyperinflammatory responses during lipopolysaccharide (LPS)-induced sepsis in mice. Sixty male Balb/c mice were randomly categorized into five groups of 12 animals each: control, intraperitoneally injected with OLE (50 mg/kg), injected with LPS (10 mg/kg, intraperitoneal), and two groups administered OLE (25 and 50 mg/kg) for 3 days prior to LPS injection. Twenty-four hours after lipopolysaccharide injection, the animals were sacrificed. Serum, liver, and kidney tissue samples were collected for biochemical analyses, histopathological examinations, and investigation of inflammation-related gene expression. OLE pretreatment significantly reduced liver damage parameters (alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase) and kidney damage parameters (blood urea nitrogen, creatinine, and kidney injury molecule-1) in the septic mice. OLE pretreatment ameliorated LPS-induced liver and kidney histological changes. OLE significantly mitigated the increased levels of malondialdehyde in the liver and kidneys and reduced levels of reduced glutathione induced by LPS. LPS injection also resulted in increased expression of the proinflammatory cytokines (TNF-α, IL-1ß, and IL-6) and inflammation-related genes (Nos2, Hmgb1, Mpo, Cd46, Map2k4, and Map2k7) in the hepatic and renal tissues. OLE reduced these expressions to ameliorate the inflammatory response. Moreover, OLE pretreatment enhanced the survival rate of septic mice. In conclusion, OLE alleviated the inflammatory response to protect against LPS-induced sepsis in mice.

Royal jelly mitigates cadmium-induced neuronal damage in mouse cortex.

This study aimed to evaluate the potential neuroprotective effect of royal jelly (RJ) against Cd-induced neuronal damage. Twenty-eight adult mice were placed equally into four groups. The control group received intraperitoneal (IP) injections of normal saline; the cadmium chloride (CdCl2) group was IP-injected 6.5 mg/kg (mg per kg of bodyweight) CdCl2; the RJ group was gavaged 85 mg/kg RJ; and the RJ + CdCl2 group was orally administered 85 mg/kg RJ 2 h before receiving IP-injections of 6.5 mg/kg CdCl2. All groups were treated for seven consecutive days and the mice were decapitated 24 h after the final dose. Cd accumulation was recorded in the cortical homogenates, accompanied by elevated levels of lipid peroxidation, nitric oxide, tumor necrosis factor-α, interleukin-1ß, and the pro-apoptotic mRNA Bax and caspase-3. Meanwhile, significantly decreased levels of detoxifying antioxidant enzymes including GSH-Px, GSH-R, SOD, and CAT, anti-apoptotic mRNA Bcl-2, and monoamines such as norepinephrine, dopamine, and serotonin were also observed, along with reduced gene expression of Nrf2-dependent antioxidants. Interestingly, in mice pretreated with RJ, the assessed parameters remained near normal levels. Our data provide evidence that RJ treatment has the potential to protect cortical neurons in Cd-intoxicated mice via its antioxidant, anti-inflammatory, anti-apoptotic, and neuromodulatory activity.

Anti-Inflammatory and Anti-Hyperuricemic Functions of Two Synthetic Hybrid Drugs with Dual Biological Active Sites.

The present study aimed to test the anti-inflammatory and xanthine oxidase inhibitory activities of two synthesized molecules and compare them to routinely prescribed nonsteroidal anti-inflammatory drugs (NSAIDs), such as diclofenac and the serum urate-lowering drug, allopurinol. The anti-inflammatory effects of the designed compounds (A and B) were evaluated in carrageenan (CAR)-induced paw edema in mice. The levels of nitric oxide and myeloperoxidase activity were measured in paw skin using biochemical methods. Additionally, prostaglandin E2 (PGE2), C-reactive protein (CRP), cyclooxygenase-2 (Cox-2), tumor necrosis factor-α (TNFα), interleukin (IL)-1ß, IL-2 and IL-10, and monocyte chemoattractant protein-1 (MCP1) were assessed by enzyme-linked immunosorbent assay (ELISA). The expression of inflammation-related genes was confirmed by real-time qPCR. The expression of inducible nitric oxide synthase (iNOS) and nuclear factor-kappa B (NF-κB) were estimated using immunohistochemistry, and xanthine oxidase inhibitory activity was evaluated using an in vitro assay. The results revealed that compounds A and B decreased inflammation, as was observed by a reduction in the elevation of all the tested markers. In addition, the tested compounds markedly decreased paw swelling, mobilization of inflammatory cells, iNOS-, and NF-κB-immunoreactive cells in a mouse model of paw edema. Interestingly, both compounds were potent xanthine oxidase inhibitors as well as Cox inhibitors with higher activity in favor of compound B providing potential dual acting series of anti-hyperuricemic and anti-inflammatory therapeutic agents.

Royal Jelly Abrogates Cadmium-Induced Oxidative Challenge in Mouse Testes: Involvement of the Nrf2 Pathway.

The current study examined the efficacy of royal jelly (RJ) against cadmium chloride (CdCl2)-induced testicular dysfunction. A total of 28 Swiss male mice were allocated into four groups (n = 7), and are listed as follows: (1) the control group, who was intraperitoneally injected with physiological saline (0.9% NaCl) for 7 days; (2) the RJ group, who was orally supplemented with RJ (85 mg/kg daily equivalent to 250 mg crude RJ) for 7 days; (3) the CdCl2 group, who was intraperitoneally injected with 6.5 mg/kg for 7 days; and (4) the fourth group, who was supplemented with RJ 1 h before CdCl2 injection for 7 days. Cd-intoxicated mice exhibited a decrease in serum testosterone, luteinizing hormone (LH), and follicle stimulating hormone (FSH) levels. A disturbance in the redox status in the testicular tissue was recorded, as presented by the increase in lipid peroxidation and nitrate/nitrite levels and glutathione (GSH) depletion. Moreover, the activities of glutathione peroxidase (GPx), glutathione reductase (GR), superoxide dismutase (SOD), catalase (CAT), and nuclear factor (erythroid-derived 2)-like-2 factor (Nrf2) and their gene expression were inhibited. In addition, interleukin-1ß (IL-1ß) and tumor necrosis factor-α (TNF-α) levels were elevated. Furthermore, Cd triggered an apoptotic cascade via upregulation of caspase-3 and Bax and downregulation of Bcl-2. Histopathological examination showed degenerative changes in spermatogenic cells, detachment of the spermatogenic epithelium from the basement membrane, and vacuolated seminiferous tubules. Decreased cell proliferation was reflected by a decrease in proliferating cell nuclear antigen (PCNA) expression. Interestingly, RJ supplementation markedly minimized the biochemical and molecular histopathological changes in testes tissue in response to Cd exposure. The beneficial effects of RJ could be attributed to its antioxidative properties.

Mapping the Interaction Landscape of Adenosine and Minoxidil Sulfate Using an Independent Gradient Model Based on Hirshfeld Partition and Interaction Region Indicator.

Using theoretical techniques, the interactions between adenosine (AD) and minoxidil sulfate (MS) were studied using the DFT/M06-2X/aug-cc-pVDZ level of theory. The formation of the complex was thermodynamically favorable, so we carried out further studies. Frontier molecular orbital analysis shows that the HOMO-LUMO- gap is high (6.81 eV), which means that the complex is kinetically stable. The global reactivity parameters were also calculated to get insight about the chemical reactivity of the complex. Molecular electrostatic potential and charge analyses were carried out for the optimized complex. To study the charge transfer and inter- and intramolecular interactions present in the complex molecule, we employed natural bond orbital analysis. Noncovalent interaction (NCI) analysis along with IGMH and IRI analyses further helped us find the weak interactions. The presence of hydrogen bonds between the N atom (N27) of MS and H atom (H66) of AD and O atom (O32) of MS and H atom (H46) of AD was the main finding of these analyses. QTAIM investigation also supports this finding. EDA analysis was carried out to further study the intermolecular interactions present within the complex. Thus, the present investigation unveils the existence of weak NCIs in the complex.

Molecular screening and genetic diversity of tick-borne pathogens associated with dogs and livestock ticks in Egypt.

BACKGROUND: The Middle East and North Africa (MENA) offer optimal climatic conditions for tick reproduction and dispersal. Research on tick-borne pathogens in this region is scarce. Despite recent advances in the characterization and taxonomic explanation of various tick-borne illnesses affecting animals in Egypt, no comprehensive examination of TBP (tick-borne pathogen) statuses has been performed. Therefore, the present study aims to detect the prevalence of pathogens harbored by ticks in Egypt. METHODOLOGY/PRINCIPAL FINDINGS: A four-year PCR-based study was conducted to detect a wide range of tick-borne pathogens (TBPs) harbored by three economically important tick species in Egypt. Approximately 86.7% (902/1,040) of the investigated Hyalomma dromedarii ticks from camels were found positive with Candidatus Anaplasma camelii (18.8%), Ehrlichia ruminantium (16.5%), Rickettsia africae (12.6%), Theileria annulata (11.9%), Mycoplasma arginini (9.9%), Borrelia burgdorferi (7.7%), Spiroplasma-like endosymbiont (4.0%), Hepatozoon canis (2.4%), Coxiella burnetii (1.6%) and Leishmania infantum (1.3%). Double co-infections were recorded in 3.0% (27/902) of Hy. dromedarii ticks, triple co-infections (simultaneous infection of the tick by three pathogen species) were found in 9.6% (87/902) of Hy. dromedarii ticks, whereas multiple co-infections (simultaneous infection of the tick by ≥ four pathogen species) comprised 12% (108/902). Out of 1,435 investigated Rhipicephalus rutilus ticks collected from dogs and sheep, 816 (56.9%) ticks harbored Babesia canis vogeli (17.1%), Rickettsia conorii (16.2%), Ehrlichia canis (15.4%), H. canis (13.6%), Bo. burgdorferi (9.7%), L. infantum (8.4%), C. burnetii (7.3%) and Trypanosoma evansi (6.6%) in dogs, and 242 (16.9%) ticks harbored Theileria lestoquardi (21.6%), Theileria ovis (20.0%) and Eh. ruminantium (0.3%) in sheep. Double, triple, and multiple co-infections represented 11% (90/816), 7.6% (62/816), and 10.3% (84/816), respectively in Rh. rutilus from dogs, whereas double and triple co-infections represented 30.2% (73/242) and 2.1% (5/242), respectively in Rh. rutilus from sheep. Approximately 92.5% (1,355/1,465) of Rhipicephalus annulatus ticks of cattle carried a burden of Anaplasma marginale (21.3%), Babesia bigemina (18.2%), Babesia bovis (14.0%), Borrelia theleri (12.8%), R. africae (12.4%), Th. annulata (8.7%), Bo. burgdorferi (2.7%), and Eh. ruminantium (2.5%). Double, triple, and multiple co-infections represented 1.8% (25/1,355), 11.5% (156/1,355), and 12.9% (175/1,355), respectively. The detected pathogens' sequences had 98.76-100% similarity to the available database with genetic divergence ranged between 0.0001 to 0.0009% to closest sequences from other African, Asian, and European countries. Phylogenetic analysis revealed close similarities between the detected pathogens and other isolates mostly from African and Asian countries. CONCLUSIONS/SIGNIFICANCE: Continuous PCR-detection of pathogens transmitted by ticks is necessary to overcome the consequences of these infection to the hosts. More restrictions should be applied from the Egyptian authorities on animal importations to limit the emergence and re-emergence of tick-borne pathogens in the country. This is the first in-depth investigation of TBPs in Egypt.

HFIP-Mediated Dual C(Ar)-Alkylation Process Towards the Regioselective Synthesis of Triarylmethanes (TRAMs).

The distinct roles of different chemical species are essential for the discovery of novel chemical transformations in organic synthesis. Here, we have designed a potential strategy for the synthesis of triarylmethanes (TRAMs) using the dual C(aryl)-alkylation process. This protocol was influenced by 1,1,1,3,3,3-hexafluoroisopropanol (HFIP) as a pivotal reagent and proceeds through the selective para C-H functionalization method. The described approach has been proven to be highly efficient in terms of substrate scope with excellent functional group tolerance and gram scale synthesis of the desired product with 90 % yield. The recyclability and reusability of HFIP has enhanced the feasibility of this protocol towards the sustainable synthesis of TRAMs.

Impact of the tripartite interaction between rice, sheath blight and diverse crop-associated endophytes on phenotypic and biochemical responses in rice.

Endophytes stimulate plant growth and inhibit phytopathogens. Most of the known endophytes are host-specific and only a few strains are effective for practical field use. Thus, this study focuses on the evaluation of endophytes viz., Bacillus pseudomycoides strain HP3d, Paenibacillus polymyxa strain PGSS1, B. velezensis strain A6 and P42 isolated from diverse crop ecosystems for their potential to promote plant growth and induce systemic resistance against sheath blight disease in rice. The endophytes were studied for plant growth promoting traits in vivo conditions and were found to exhibit ammonia (light to strong), siderophore (yellow zone on the CAS agar plate), indole-3-acetic acid (15.20-22.19 µg mL-1) production and phosphorus solubilization (1.2-1.5 cm). In the glasshouse, when applied individually and in combinations through various methods like seed treatment, seedling dip, and foliar spray these endophytes significantly reduced lesion size (2.06-2.37 fold) and ShB severity (2.60-2.58 fold), enhancing growth parameters viz., shoot (1.09-1.11 fold), root (1.02-1.20 fold), number of tillers (1.2-1.6 fold), shoot (80.58-82.64 %) and root (62.01-66.66 %) dry matter over untreated control. Consequently, enzyme activity viz., polyphenol oxidase (2.20-3.00 U-1min-1g-1), peroxidase (0.31-0.35 min-1g-1), superoxide dismutase (118.50-123.00 Ug-1 FW), and phenylalanine ammonia lyase (0.84-0.90 min⁻1g⁻1FW) was found to increase up to the fourth day after the pathogen challenge and subsequently decrease thereafter. Chlorophyll content post inoculation of ShB declined over time but endophyte treated plants exhibited lesser reductions over uninoculated control. Field trials corroborated the in vitro findings, demonstrating reduced ShB (1.71-1.88 fold decrease in PDI) and enhanced growth (1.1-1.2 fold increase in shoot length) over untreated controls. The combined application of seedling dip, seed treatment, and foliar spray proved to be the most optimum treatment. The findings highlight the potential of diverse crop-derived endophytes, emphasizing their non-host specificity and effectiveness as broad-spectrum bioagents in actual field conditions.

Oral administration of proniosomal glibenclamide formulation protects testicular tissue from hyperglycemia fluctuations and ROS via Nrf2/HO-1 pathway.

Type 2 diabetes causes high blood sugar due to insulin malfunction and is linked to male infertility. Using proniosomes can enhance the effectiveness of Glibenclamide, a medication that stimulates insulin secretion. In our study, male rats with diabetes were treated with GLB with or without proniosomal for 14 days. Proniosomal formulations maintained glucose levels prevented weight loss and showed normal testicular tissue. GLB-proniosomal reduces ROS caused by T2DM through Nrf2, HO-1 pathway and increases CAT, SOD, and GSH production in response to insulin and glucose uptake. The reference and proniosomal treatments showed CAT and SOD significant enzymatic elevation compared to the positive and negative control. CAT significantly correlated with Gpx4 expression with P = 0.0169 and r = 0.98; similarly, the enzymatic activity of SOD also showed a positive correlation between the average glucose levels (r = 0.99 and P = 0.0037). Intestinally, GSH analysis revealed that only proniosomal-GLB samples are significantly elevated from the positive control, with a P value of 0.0210. The data showed proniosomal-GLB was more effective than pure GLB, confirmed by higher Nrf2 (2.050 folds), HO-1 (2.148 folds), and GPx4 (1.9 folds) transcript levels relative to the control with less sample diversity compared to the reference samples, indicating proniosomal stabilized GLB in the blood. Administering GLB and proniosomes formulation has effectively restored testicular function and sperm production in diabetic rats by regulating ROS levels and upregulating anti-ROS in response to glucose uptake. These findings may lead to better treatments for diabetic patients who have infertility issues.

Determination of dose- and time-dependent hepatotoxicity and apoptosis of Lanthanum oxide nanoparticles in female Swiss albino mice.

Nanosized lanthanum oxide particles (La2O3) are commonly utilized in various industries. The potential health risks associated with La2O3 nanoparticles, cytotoxic effects at varying doses and time intervals, and the mechanisms behind their induction of behavioral changes remain uncertain and necessitate further investigation. Therefore, this study examined in vivo hepatotoxicity, considering the quantity (60, 150, and 300 mg/kg) and time-dependent induction of reactive oxygen species (ROS) over one week or 21 days. The mice received intraperitoneal injections of three different concentrations in Milli-Q water. Throughout the experiments, no physical changes or weight loss were observed among the groups. However, after 21 days, only the highest concentration showed signs of anxiety in the activity cage (p < 0.05). Subsequently, all animals treated with La2O3 NPs exhibited a significant loss of learning and memory recall using the Active Avoidances test, after 21 days (p < 0.001). Markers for anti-reactive oxygen species (ROS) such as superoxide dismutase (SOD) were significantly upregulated in response to all concentrations of NPs after seven days compared to the control group. This was confirmed by a significant increase in glutathione peroxidase (Gpx1) and pro-apoptotic Caspase-3 expression at the lowest and highest doses. Additionally, both transcription and protein levels of the anti-apoptotic BCL-2 surpassed P53 protein in a dosage-dependent manner, indicating activation of the primary anti-apoptosis pathway. After 21 days, P53 levels exceeded BCL-2 protein levels, confirming a significant loss of BCL-2 mRNA, particularly at the 300 mg/kg concentration. Furthermore, a higher transcription level of Caspase-3, SOD, and Gpx1 was observed, with the highest values detected at the 300 mg/kg concentration, indicating the activation of cell death. Histopathological analysis of the liver illustrated apoptotic bodies resulting from La2O3 NP concentration. The investigation revealed multiple inflammatory foci, cytoplasmic degeneration, steatosis, and DNA fragmentation consistent with increased damage over time due to higher concentrations. Blood samples were also analyzed to determine liver enzymatic changes, including alkaline phosphatase (ALP), alanine transaminase (ALT), aspartate aminotransferase (AST), and lipid profiles. The results showed significant differences among all La2O3 NP concentrations, with the most pronounced damage observed at the 300 mg/kg dose even after 21 days. Based on an animal model, this study suggests that La2O3 hepatotoxicity is likely caused by the size and shape of nanoparticles (NPs), following a dose and time-dependent mechanism that induces the production of reactive oxygen species and behavioral changes such as anxiety and memory loss.

Corrigendum: The outbreak of seasonal goat's brucellosis in the Swat ecosystem of Khyber Pakhtunkhwa.

No abstract available.

The protective effect of apigenin against inorganic arsenic salt-induced toxicity in PC12 cells.

Poisoning by arsenic affects people worldwide, and many human illnesses and health issues, including neurotoxicity, have been linked to chronic exposure to arsenic. When exposed to arsenic, the body produces intracellular reactive oxygen species (ROS), which influence a variety of alterations in cellular activity and directly harm molecules through oxidation. Arsenic-induced lesions are improved by antioxidants with the ability to lower ROS levels. Therefore, the current research aimed to assess how well apigenin protected PC12 cells from the toxicity caused by inorganic arsenic salt (iAs). For 24 and 48 h, iAs and/or apigenin were applied to PC12 cells. Then, oxidative stress indicators like malondialdehyde (MDA), nitric oxide (NO), and ROS in addition to the enzymatic and non-enzymatic antioxidant molecules such as catalase (CAT), glutathione (GSH), and superoxide dismutase (SOD) were assessed. Moreover, after exposure to iAs, PC12 was examined for nuclear factor erythroid 2-related factor 2 (Nrf2) expression to clarify how apigenin manifests its neuroprotection. Furthermore, NF-kB p65 concentration and IL-1B, IL-6, and TNF-α mRNA expression were measured to assess neuroinflammation. Bax, caspase-3, and Bcl-2 levels were measured to investigate apigenin's potential to protect PC12 cells from iAs poisoning. The obtained results revealed that, the cell survival rate in the iAs group was significantly lower (P < 0.05), and the number of viable cells steadily increased after apigenin treatment. Furthermore, the study found that iAs decreased GSH, CAT, and SOD in the PC12 cells while increasing ROS, MDA, and NO levels. In PC12 cells, the capacity of iAs to cause oxidative stress was linked to the induction of neuroinflammation and apoptosis. Interestingly, apigenin pre-treatment of PC12 cells resulted in exceptional protection against iAs-induced neuroinflammation, oxidative stress, and apoptotic cell death. Nrf2 upregulation in PC12 cells may explain the neuroprotection effect of apigenin against iAs toxicity. In conclusion, the obtained results of the present study have clinical significance and indicate that apigenin is a promising candidate for shielding the nervous system from toxic effects caused by arsenic. These findings require further investigation using in vivo experimental models.

Renal-protective effect of Asparagus officinalis aqueous extract against lead-induced nephrotoxicity mouse model.

Lead is one of the cursed substances that threaten all human life. Lead poisoning can occur through food or water contaminations and it is hard to be detected. This incognito metal accumulates over time and resides in the liver, kidneys, and brain tissues leading to serious medical conditions, affecting organ functions, causing failure, kidney tubule degeneration, and destroying neuronal development. However, known metal chelators have bad negative effects. Asparagus officinalis (AO) is a promising herb; its root extract exhibited antioxidant, antiapoptotic, protective, and immunomodulatory activities. Inspired by those reasons, this study investigated to which extent Asparagus extract affected male mice's renal toxicity caused by lead acetate (LA) and antioxidant defense system. This work screened for its nephroprotective activity in four mouse groups: negative and positive control, LA group with renal injury, and diseased but pretreated mice with AO extract (AOE). Kidney index and kidney function biomarkers were evaluated. Antioxidant activities, lipid peroxidation, superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GR), glutathione peroxidase (GPx), nitric oxide (NO), and reduced glutathione (GSH) were also tested. Furthermore, inflammatory cytokine (tumor necrosis factor-α (TNF-α), interleukin-1 ß (IL-1ß), and the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB)), inducible nitric oxide synthase (iNOS), renal pro-apoptotic protein (Bax), antiapoptotic protein (Bcl-2), and caspase-3 levels were evaluated. The results showed that LA administration induced oxidative stress, renal inflammation, apoptosis, and renal histopathological alteration. However, due to its antioxidant activities, AOE was found to restrain oxidative stress, therefore preventing inflammation and apoptosis. Collectively, AOE perfectly clogged lead poisoning sneaking, stopped the bad deterioration, and succeeded to protect kidney tissues from toxicity, inflammation, and apoptosis.