Potential Surviving Effect of Cleome droserifolia Extract against Systemic Staphylococcus aureus Infection: Investigation of the Chemical Content of the Plant.

The increasing rates of morbidity and mortality owing to bacterial infections, particularly Staphylococcus aureus have necessitated finding solutions to face this issue. Thus, we elucidated the phytochemical constituents and antibacterial potential of Cleome droserifolia extract (CDE). Using LC-ESI-MS/MS, the main phytoconstituents of CDE were explored, which were kaempferol-3,7-O-bis-alpha-L-rhamnoside, isorhamnetin, cyanidin-3-glucoside, kaempferide, kaempferol-3-O-alpha-L-rhamnoside, caffeic acid, isoquercitrin, quinic acid, isocitrate, mannitol, apigenin, acacetin, and naringenin. The CDE exerted an antibacterial action on S. aureus isolates with minimum inhibitory concentrations ranging from 128 to 512 µg/mL. Also, CDE exhibited antibiofilm action using a crystal violet assay. A scanning electron microscope was employed to illuminate the effect of CDE on biofilm formation, and it considerably diminished S. aureus cell number in the biofilm. Moreover, qRT-PCR was performed to study the effect of CDE on biofilm gene expression (cna, fnbA, and icaA). The CDE revealed a downregulating effect on the studied biofilm genes in 43.48% of S. aureus isolates. Regarding the in vivo model, CDE significantly decreased the S. aureus burden in the liver and spleen of CDE-treated mice. Also, it significantly improved the mice's survival and substantially decreased the inflammatory markers (interleukin one beta and interleukin six) in the studied tissues. Furthermore, CDE has improved the histology and tumor necrosis factor alpha immunohistochemistry in the liver and spleen of the CDE-treated group. Thus, CDE could be considered a promising candidate for future antimicrobial drug discovery studies.

Antibacterial potential of Euphorbia canariensis against Pseudomonas aeruginosa bacteria causing respiratory tract infections.

The widespread dissemination of bacterial resistance has led to great attention being paid to finding substitutes for traditionally used antibiotics. Plants are rich in various phytochemicals that could be used as antibacterial therapies. Here, we elucidate the phytochemical profile of Euphorbia canariensis ethanol extract (EMEE) and then elucidate the antibacterial potential of ECEE against Pseudomonas aeruginosa clinical isolates. ECEE showed minimum inhibitory concentrations ranging from 128 to 512 µg/mL. The impact of ECEE on the biofilm-forming ability of the tested isolates was elucidated using crystal violet assay and qRT-PCR to study its effect on the gene expression level. ECEE exhibited antibiofilm potential, which resulted in a downregulation of the expression of the biofilm genes (algD, pelF, and pslD) in 39.13% of the tested isolates. The antibacterial potential of ECEE was studied in vivo using a lung infection model in mice. A remarkable improvement was observed in the ECEE-treated group, as revealed by the histological and immunohistochemical studies. Also, ELISA showed a noticeable decrease in the oxidative stress markers (nitric oxide and malondialdehyde). The gene expression of the proinflammatory marker (interleukin-6) was downregulated, while the anti-inflammatory biomarker was upregulated (interleukin-10). Thus, clinical trials should be performed soon to explore the potential antibacterial activity of ECEE, which could help in our battle against resistant pathogenic bacteria.

A new polycyclic tetramate macrolactam from Allostreptomyces RD068384: stereochemistry and antifungal potential.

A new polycyclic tetramate macrolactam designated allostreptamide (1), together with four known congeners, were isolated from the culture extract of Allostreptomyces RD068384. The planar structure of the new compound was elucidated through interpretation of NMR and MS data. The absolute configuration was determined through ROESY and ECD analyses. The isolated compounds revealed antifungal potential against fourteen Candida albicans isolates with minimum inhibitory concentrations (MICs) ranging from 64 to 2048 µg ml-1. Compound 3 showed antibiofilm action and considerably reduced the viability of five isolates (36%) in the formed biofilm. The qRT-PCR revealed that 3 downregulated the BCR1, PLB2, ALS1, and SAP5 biofilm related gene expression. Therefore, 3 could be a promising antifungal therapy for C. albicans infections.

Investigation of bioactive components responsible for the antibacterial and anti-biofilm activities of Caroxylon volkensii by LC-QTOF-MS/MS analysis and molecular docking.

Caroxylon volkensii is a wild desert plant of the family Amaranthaceae. This study represents the first report of the metabolomic profiling of C. volkensii by liquid chromatography quadrupole-time-of-flight tandem mass spectrometry (LC-QTOF-MS/MS). The dereplication study of its secondary metabolites led to the characterization of 66 known compounds. These compounds include catecholamines, tyramine derivatives, phenolic acids, triterpenoids, flavonoids, and others. A new tyramine derivative, alongside other known compounds, was reported for the first time in the Amaranthaceae family. The new derivative and the first-reported compounds were putatively identified through MS/MS fragmentation data. Given the notorious taxonomical challenges within the genus Salsola, to which C. volkensii previously belonged, our study could offer a valuable insight into its chemical fingerprint and phylogenetic relationship to different Salsola species. The antibacterial potential of C. volkensii methanolic extract (CVM) against Pseudomonas aeruginosa was screened. The minimum inhibitory concentration (MIC) of CVM ranged from 32 to 256 µg mL-1. The anti-quorum sensing potential of CVM resulted in a decrease in the percentage of strong and moderate biofilm-forming isolates from 47.83% to 17.39%. It revealed a concentration-dependent inhibitory activity on violacein formation by Chromobacterium violaceum. Moreover, CVM exhibited an in vivo protective potential against the killing capacity of P. aeruginosa isolates. A molecular docking study revealed that the quorum-sensing inhibitory effect of CVM can be attributed to the binding of tyramine conjugates, ethyl-p-digallate, and isorhamnetin to the transcriptional global activator LasR.

Next-generation probiotics: the upcoming biotherapeutics.

Recent and continuing advances in gut microbiome research have pointed out the role of the gut microbiota as an unexplored source of potentially beneficial probiotic microbes. Along the lines of these advances, both public awareness and acceptance of probiotics are increasing. That's why; academic and industrial research is dedicated to identifying and investigating new microbial strains for the development of next-generation probiotics (NGPs). At this time, there is a growing interest in NGPs as biotherapeutics that alter the gut microbiome and affect various diseases development. In this work, we have focused on some emergent and promising NGPs, specifically Eubacterium hallii, Faecalibacterium prausnitzii, Roseburia spp., Akkermansia muciniphila, and Bacteroides fragilis, as their presence in the gut can have an impact on the development of various diseases. Emerging studies point out the beneficial roles of these NGPs and open up novel promising therapeutic options. Interestingly, these NGPs were found to enhance gastrointestinal immunity, enhance immunotherapy efficacy in cancer patients, retain the intestinal barrier integrity, generate valuable metabolites, especially short-chain fatty acids, and decrease complications of chemotherapy and radiotherapy. Although many of these NGPs are considered promising for the prevention and treatment of several chronic diseases, research on humans is still lacking. Therefore, approval of these microbes from regulatory agencies is rare. Besides, some issues limit their wide use in the market, such as suitable methods for the culture and storage of these oxygen-sensitive microbes. The present review goes over the main points related to NGPs and gives a viewpoint on the key issues that still hinder their wide application. Furthermore, we have focused on the advancement in NGPs and human healthiness investigations by clarifying the limitations of traditional probiotic microorganisms, discussing the characteristics of emerging NGPs and defining their role in the management of certain ailments. Future research should emphasize the isolation, mechanisms of action of these probiotics, safety, and clinical efficacy in humans.

Role of GABA pathway in motor and non-motor symptoms in Parkinson's disease: a bidirectional circuit.

Parkinson's disease (PD) is a progressive neurodegenerative disease as a result of the degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNpc). The fundamental features of PD are motor and non-motor symptoms. PD symptoms develop due to the disruption of dopaminergic neurotransmitters and other neurotransmitters such as γ-aminobutyric acid (GABA). The potential role of GABA in PD neuropathology concerning the motor and non-motor symptoms of PD was not precisely discussed. Therefore, this review intended to illustrate the possible role of GABA in PD neuropathology regarding motor and non-motor symptoms. The GABA pathway is essential in regulating the inhibitory tone to prevent excessive stimulation of the cerebral cortex. Degeneration of dopaminergic neurons in PD is linked with reducing GABAergic neurotransmission. Decreasing GABA activity promotes mitochondrial dysfunction and oxidative stress, which are highly related to PD neuropathology. Hence, restoring GABA activity by GABA agonists may attenuate the progression of PD motor symptoms. Therefore, dysregulation of GABAergic neurons in the SNpc contributes to developing PD motor symptoms. Besides, PD non-motor symptoms are also related to the dysfunction of the GABAergic pathway, and amelioration of this pathway may reduce PD non-motor symptoms. In conclusion, the deregulation of the GABAergic pathway in PD might be intricate in developing motor and non-motor symptoms. Improving this pathway might be a novel, beneficial approach to control PD symptoms.

Dioon rzedowskii: An antioxidant, antibacterial and anticancer plant extract with multi-faceted effects on cell growth and molecular signaling.

This study investigated the antioxidant, anticancer, antibacterial properties of Dioon rzedowskii extract, which had not been previously explored. We aimed to determine the extract's effect on liver and breast cancer cell lines and on solid Ehrlich carcinoma (SEC) mouse model to investigate the underlying molecular mechanisms. Three female albino mice groups were established: a tumor control group, a group treated with 100 mg/kg of the extract (D100), and a group treated with 200 mg/kg of the extract (D200) for 16 days after tumor development. Results showed that the D. rzedowskii extract inhibited cell growth in both MCF-7 and HepG2 cells in a concentration-dependent manner. This was achieved by suppressing the cell proliferation and inducing apoptosis. The extract also improved liver, heart, and kidney functions compared to the tumor control. Furthermore, oral administration of the extract reduced tumor volume and alleviated oxidative stress in tumor tissue. The anticancer effects were associated with overexpression of p53 and Bax and downregulation of cyclin D1 expression, which was attributed to decreased phosphorylated MAPK kinases. Additionally, D. rzedowskii exhibited antibacterial activity against K. pneumoniae isolated from cancer patients. The extract inhibited bacterial growth and reduced the membrane integrity. The study suggests that D. rzedowskii has promising potential as an adjunctive therapy for cancer treatment. Further investigations are needed to explore its combined anticancer efficacy. These results emphasize the value of natural products in developing compounds with potential anticancer activity and support a paradigm shift in cancer management to improve patients' quality of life.

Outlining the Phytoconstituents of Greek Clover Herb Extract and Assessment of Its Effect against Foodborne Infections Caused by Salmonella typhimurium.

Owing to the spread of resistance between pathogenic bacteria, searching for novel compounds with antibacterial activity is essential. Here, we investigated the potential antibacterial activity of Greek clover or Trigonella foenum-graecum herb extract on Salmonella typhimurium clinical isolates. The chemical profile of the herb was initially determined using LC-ESI-MS/MS, which explored 36 different compounds. Interestingly, the fenugreek extract possessed antibacterial action in vitro with minimum inhibitory concentrations of 64 to 512 µg/mL. The potential mechanism of action was studied by elucidating the effect of the fenugreek extract on the membrane properties of S. typhimurium bacteria, including the inner and outer membrane permeability and membrane integrity. Remarkably, the fenugreek extract had detrimental effects on the membrane properties in 40-60% of the isolates. Moreover, the in vivo antibacterial action was studied using a gastrointestinal infection model with S. typhimurium bacteria. Interestingly, the fenugreek extract (200 mg/kg) improved the infection outcomes in the tested mice. This was represented by the noteworthy decrease (p < 0.05) in the bacterial count in the small intestine and caecum tissues. The survival rate of the fenugreek-extract-treated mice significantly increased compared to the S. typhimurium-infected group. Additionally, there was an improvement in the histological and immunohistochemical features of tumor necrosis factor-alpha. In addition, using an ELISA and qRT-PCR, there was an improvement in the proinflammatory and oxidative stress markers in the fenugreek-extract-treated group. Consequently, fenugreek extract should be investigated further on other food pathogens.

Design, synthesis, molecular docking, and in vitro studies of 2-mercaptoquinazolin-4(3H)-ones as potential anti-breast cancer agents.

Triple-negative breast cancer (TNBC) comprises 10 % to 20 % of breast cancer, however, it is more dangerous than other types of breast cancer, because it lacks druggable targets, such as the estrogen receptors (ER) and the progesterone receptor (PR), and has under expressed receptor tyrosine kinase, ErbB2. Present targeted therapies are not very effective and other choices include invasive procedures like surgery or less invasive ones like radiotherapy and chemotherapy. This study investigated the potential anticancer activity of some novel quinazolinone derivatives that were designed on the structural framework of two approved anticancer drugs, Ispinesib (KSP inhibitor) and Idelalisib (PI3Kδ inhibitor), to find out solutions for TNBC. All the designed derivatives (3a-l) were subjected to extra precision molecular docking and were synthesized and spectrally characterized. In vitro enzyme inhibition assay of compounds (3a, 3b, 3e, 3 g and 3 h) revealed their nanomolar inhibitory potential against the anticancer targets, KSP and PI3Kδ. Using MTT assay, the cytotoxic potential of compounds 3a, 3b and 3e were found highest against MDA-MB-231 cells with an IC50 of 14.51 µM, 16.27 µM, and 9.97 µM, respectively. Remarkably, these compounds were recorded safe against the oral epithelial normal cells with an IC50 values of 293.60 µM, 261.43 µM, and 222 µM, respectively. The anticancer potential of these compounds against MDA-MB-231 cells was revealed to be associated with their apoptotic activity. This was established by examination with the inverted microscope that revealed the appearance of various apoptotic features like cell shrinkage, apoptotic bodies, and membrane blebbing. Using flow cytometry, the Annexin V/PI-stained cancer cells showed an increase in early and late apoptotic cells. In addition, DNA fragmentation was revealed to occur after treatment with the tested compounds by gel electrophoresis. The relative gene expression of pro-apoptotic and anti-apoptotic genes revealed an overexpression of the P53 and BAX genes and a downregulation of the BCL-2 gene by real-time PCR. So, this work proved that compounds 3a, 3b, and 3e could be developed as anticancer candidates, via their P53-dependent apoptotic activity.

Role of fenofibrate in multiple sclerosis.

Multiple sclerosis (MS) is the most frequent inflammatory and demyelinating disease of the central nervous system (CNS). The underlying pathophysiology of MS is the destruction of myelin sheath by immune cells. The formation of myelin plaques, inflammation, and injury of neuronal myelin sheath characterizes its neuropathology. MS plaques are multiple focal regions of demyelination disseminated in the brain's white matter, spinal cords, deep grey matter, and cerebral cortex. Fenofibrate is a peroxisome proliferative activated receptor alpha (PPAR-α) that attenuates the inflammatory reactions in MS. Fenofibrate inhibits differentiation of Th17 by inhibiting the expression of pro-inflammatory signaling. According to these findings, this review intended to illuminate the mechanistic immunoinflammatory role of fenofibrate in mitigating MS neuropathology. In conclusion, fenofibrate can attenuate MS neuropathology by modulating different pathways, including oxidative stress, autophagy, mitochondrial dysfunction, inflammatory-signaling pathways, and neuroinflammation.

Rosuvastatin and diosmetin inhibited the HSP70/TLR4 /NF-κB p65/NLRP3 signaling pathways and switched macrophage to M2 phenotype in a rat model of acute kidney injury induced by cisplatin.

Numerous efforts to manage acute kidney injury (AKI) were unsuccessful because its pathophysiology is still poorly understood. Thus, our research hotspot was to explore the possible renoprotective effects of rosuvastatin (Ros) and diosmetin (D) on macrophage polarization and the role of HSP70/TLR4/MyD88/NF-κB p65/NLRP3/STAT3 signaling in cis-induced AKI and study the activity of D against uropathogenic bacteria. Fifty-four albino male rats were randomized into 9 groups equally: Control, Ros, D20, D40, untreated Cis, and Cis groups cotreated with Ros, D20, D40 and Ros+D40 for 10 days. Our results indicated that Ros and D, in a dose-dependent manner, markedly restored body weight, systolic blood pressure, and renal histological architecture besides significantly upregulated SOD levels, expression of anti-inflammatory CD163 macrophages, arginase1levels, IL-10 levels,STAT3 and PCNA immunoreactivity. Also, they significantly downregulated renal index, serum urea, serum creatinine, serum cystatin c, inflammatory biomarkers (C reactive protein, IL1ß & TNF-α), MDA levels, HSP70/TLR4/MyD88/NF-κB p65/NLRP3 expressions, proinflammatory CD68 macrophages and caspase-3 immunoreactivity, resulting in a reversal of cis-induced renal damage. These findings were further confirmed by molecular docking that showed the binding affinity of Ros and D towards TLR4 and NLRP3. Furthermore, D had antibacterial action with a minimum inhibitory concentration ranging from 128 to 256 µg/mL and caused a delay in the growth of the tested isolates, and negatively affected the membrane integrity. In conclusion, Ros and D had antioxidant, anti-inflammatory and antiapoptotic properties and switched macrophage from proinflammatory CD68 to anti-inflammatory CD163. Additionally, the targeting of HSP70/TLR4/MyD88/NF-κB p65/NLRP3/STAT3 signals are effective therapeutic strategy in AKI.

Studying the effects of secondary metabolites isolated from Cycas thouarsii R.Br. leaves on MDA-MB-231 breast cancer cells.

The various therapeutic drugs that are currently utilized for the management of cancer, especially breast cancer, are greatly challenged by the augmented resistance that is either acquired or de novo by the cancer cells owing to the long treatment periods. So, this study aimed at elucidating the possible anticancer potential of four compounds 7, 4', 7'', 4'''-tetra-O-methyl amentoflavone, hesperidin, ferulic acid, and chlorogenic acid that are isolated from Cycas thouarsii leaves n-butanol fraction for the first time. The MTT assay evaluated the cytotoxic action of four isolated compounds against MDA-MB-231 breast cancer cells and oral epithelial cells. Interestingly, ferulic acid revealed the lowest IC50 of 12.52 µg/mL against MDA-MB-231 cells and a high IC50 of 80.2 µg/mL against oral epithelial cells. Also, using an inverted microscope, the influence of ferulic acid was studied on the MDA-MB-231, which revealed the appearance of apoptosis characteristics like shrinkage of the cells and blebbing of the cell membrane. In addition, the flow cytometric analysis showed that the MDA-MB-231 cells stained with Annexin V/PI had a rise in the count of the cells in the early and late apoptosis stages. Moreover, gel electrophoresis detected DNA fragmentation in the ferulic acid-treated cells. Finally, the effect of the compound was tested at the molecular level by qRT-PCR. An upregulation of the pro-apoptotic genes (BAX and P53) and a downregulation of the anti-apoptotic gene (BCL-2) were observed. Consequently, our study demonstrated that these isolated compounds, especially ferulic acid, may be vital anticancer agents, particularly for breast cancer, through its induction of apoptosis through the P53-dependent pathway.

Escherichia coli isolates from meat and abattoirs environment in Egypt: molecular characterization and control by nanosilver particles.

Three hundred samples, including meat from the slaughtered carcass and water, air samples, and swabs from the floor, wall, and employees' hands, were collected from five municipal abattoirs spread across several Egyptian provinces. The Escherichia coli was isolated from floor swabs, meat, air, wall, hand, and water samples. Serotyping of the recovered isolates clarified the presence of various serotypes, including enterohemorrhagic serotypes (O111: H4, O128: H2, and O127: H6) and enterotoxigenic serotypes (O44: H18 and O125: H21). The isolates were resistant to cefotaxime (100%), amoxiclav (80%), then rifampin (66.7%). The stx1 gene, stx2 gene, eaeA gene, blaCMY2 gene and iss gene were detected in 10-80 % of the isolates. Nanosilver (AgNPs) showed that 12.5 ppm was the lowest concentration that prevented bacterial growth. It was observed that 12% of workers wore a clean white coat, only 24% washed their hands between activities during work, only 14% used soap for hand washing, and 42% utilized the same knife for meat and its offal.

Irisin/PGC-1α/FNDC5 pathway in Parkinson's disease: truth under the throes.

Parkinson's disease (PD) is considered one of the most common neurodegenerative brain diseases which involves the deposition of α-synuclein. Irisin hormone, a newly discovered adipokine, has a valuable role in diverse neurodegenerative diseases. Therefore, this review aims to elucidate the possible role of the irisin hormone in PD neuropathology. Irisin hormone has a neuroprotective effect against the development and progression of various neurodegenerative disorders by increasing the expression of brain-derived neurotrophic factor (BDNF). Irisin hormone has anti-inflammatory, anti-apoptotic, and anti-oxidative impacts, thereby reducing the expression of the pro-inflammatory cytokines and the progression of neuroinflammation. Irisin-induced PGC-1α could potentially prevent α-synuclein-induced dopaminergic injury, neuroinflammation, and neurotoxicity in PD. Inhibition of NF-κB by irisin improves PGC-1α and FNDC5 signaling pathway with subsequent attenuation of PD neuropathology. Therefore, the irisin/PGC-1α/FNDC5 pathway could prevent dopaminergic neuronal injury. In conclusion, the irisin hormone has a neuroprotective effect through its anti-inflammatory and antioxidant impacts with the amelioration of brain BDNF levels. Further preclinical and clinical studies are recommended in this regard.

Evaluation of Tamarix nilotica Fractions in Combating Candida albicans Infections.

OBJECTIVES: Evaluation of the antifungal properties of Tamarix nilotica fractions against Candida albicans clinical isolates. METHODS: The in vitro antifungal potential was evaluated by agar well diffusion and broth microdilution methods. The antibiofilm potential was assessed by crystal violet, scanning electron microscopy (SEM), and qRT-PCR. The in vivo antifungal activity was evaluated by determining the burden in the lung tissues of infected mice, histopathological, immunohistochemical studies, and ELISA. RESULTS: Both the dichloromethane (DCM) and ethyl acetate (EtOAc) fractions had minimum inhibitory concentration (MIC) values of 64-256 and 128-1024 µg/mL, respectively. SEM examination showed that the DCM fraction decreased the biofilm formation capacity of the treated isolates. A significant decline in biofilm gene expression was observed in 33.33% of the DCM-treated isolates. A considerable decline in the CFU/g lung count in infected mice was observed, and histopathological examinations revealed that the DCM fraction maintained the lung tissue architecture. Immunohistochemical investigations indicated that the DCM fraction significantly (p < 0.05) decreased the expression of pro-inflammatory and inflammatory cytokines (TNF-α, NF-kB, COX-2, IL-6, and IL-1ß) in the immunostained lung sections. The phytochemical profiling of DCM and EtOAc fractions was performed using Liquid chromatography-mass spectrometry (LC-ESI-MS/MS). CONCLUSION: T. nilotica DCM fraction could be a significant source of natural products with antifungal activity against C. albicans infections.

Phytochemical investigation, antibacterial, and ameliorative potential effects of Tamarix nilotica on LPS-induced acute lung injury model in mice.

Acute lung injury (ALI) is a serious illness with a high mortality rate of 40-60%. It is characterised by systemic inflammatory processes and oxidative stress. Gram-negative bacterial infections are the major cause of ALI, and lipopolysaccharide (LPS) is the major stimulus for the release of inflammatory mediators. Hence, there is an urgent need to develop new therapies which ameliorate ALI and prevent its serious consequences. The Middle Eastern native plant Tamarix nilotica (Ehrenb) Bunge belongs to the family Tamaricaceae, which exhibits strong anti-inflammatory and antioxidant effects. Thus, the current work aimed to ensure the plausible beneficial effects of T. nilotica different fractions on LPS-induced acute lung injury after elucidating their phytochemical constituents using LC/MS analysis. Mice were randomly allocated into six groups: Control saline, LPS group, and four groups treated with total extract, DCM, EtOAc and n-butanol fractions, respectively, intraperitoneal at 100 mg/kg doses 30 min before LPS injection. The lung expression of iNOS, TGF-ß1, NOX-1, NOX-4 and GPX-1 levels were evaluated. Also, oxidative stress was assessed via measurements of MDA, SOD and Catalase activity, and histopathological and immunohistochemical investigation of TNF-α in lung tissues were performed. T. nilotica n-butanol fraction caused a significant downregulation in iNOS, TGF-ß1, TNF-α, NOX-1, NOX-4, and MDA levels (p ˂ 0.05), and significantly elevated GPX-1 expression levels, SOD, and catalase activity (p ˂ 0.05), and alleviated all histopathological abnormalities confirming its advantageous role in ALI. The antibacterial activities of T. nilotica and its different fractions were investigated by agar well diffusion method and broth microdilution method. Interestingly, the n-butanol fraction exhibited the best antibacterial activity against Klebsiella pneumoniae clinical isolates. It also significantly reduced exopolysaccharide quantity, cell surface hydrophobicity, and biofilm formation.

Plausible Protective Role of Encephalartos villosus Extract in Acetic-Acid-Induced Ulcerative Colitis in Rats.

Ulcerative colitis (UC) is an inflammatory ailment of the intestine associated with the upregulation of oxidative stress and pro-inflammatory cytokines. Here, we aimed to assess the consequences of Encephalartos villosus (EV) Lem extract on acetic acid (AA)-induced UC. Rats were randomly classified into five groups, as follows: control, AA, AA + mesalazine, AA + EV (50 mg/kg), and AA + EV (100 mg/kg) groups. EV (50 mg/kg and 100 mg/kg) and mesalzine (100 mg/kg) were administered orally for 14 days before the induction of UC. On the last day of the experiment, colitis was provoked via the intra-rectal delivery of 3% AA. Then, after 24 h, the rats were sacrificed and their colon tissues were isolated and inspected. Interestingly, EV pretreatment substantially (p < 0.05) reduced the elevated colon weight/length ratio and ulcer area and normalized the histological changes and immunohistochemical features. In addition, EV efficiently reduced the levels of myeloperoxidase (MPO) and increased the activity of glutathione peroxidase (GS-PX) and catalase (CAT). EV (100 mg/kg) resulted in a downregulation of toll-like receptor 4 (TLR-4) and upregulation of heme oxygenase 1 (HO-1) and occludin expression levels. Concerning the anti-inflammatory mechanisms, EV reduced the levels of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and nuclear transcription factor kappa B (NF-ĸB) and inhibited cyclooxygenase-2 (COX-2) expression levels. It also decreased caspase-3 levels. Our results indicate that the oral intake of EV improves AA-induced colitis in rats through its antioxidative effects and the modulation of pro-inflammatory cytokines, as well as the restoration of mucosal integrity. Consequently, EV may be an efficient therapeutic candidate for UC.

Green synthetized Cu-Oxide Nanoparticles: Properties and applications for enhancing healing of wounds infected with Staphylococcus aureus.

Treating wound infections is a challenging concern in various clinical settings in Egypt, especially in the increasing global problem of resistance to antimicrobials. Here, we aimed to fabricate CuO NPs via green synthesis using aqueous Yucca gigantea extract. Then, the effect of green synthesized CuO NPs on Staphylococcus aureus clinical isolates has been studied in vivo and in vitro. The aqueous extract of Yucca gigantea has been employed in our study as a scale-up approach to safely, affordably, sustainably, and practically fabricate copper oxide nanoparticles (CuO NPs). Fourier transforms infrared (FT-IR), X-ray Diffraction (XRD), and UV-vis spectroscopy were utilized in vitro to describe the bonding features of CuO NPs.Scanning Electron microscopy (SEM), Transmission electron microscopy (TEM), Energy dispersive X-ray (EDX), and dynamic light scattering (DLS) were used to detect the morphological and elemental composition of the resulting CuO NPs. The fabrication of CuO NPs was confirmed by the IR spectral band at 515 cm-1, ensuring the metal-oxygen bondCu-O with two strong bands at 229 and 305 nm. SEM and TEM show CuO NPs with a size range from 30 to 50 nm. Cu and O comprised most of the particles produced through green synthesis, with weight percentages of 57.82 and 42.18 %, respectively. CuO NPs were observed to have a Zeta-potential value of -15.7 mV, demonstrating their great stability. CuO NPs revealed antibacterial potential toward the tested isolates with minimum inhibitory concentration values of 128 to 512 µg/mL. CuO NPs had antibiofilm potential by crystal violet assay, downregulating the expression of icaA and icaD genes in 23.07 % and 19.32 of the S. aureus isolates. The wound-healing potential of CuO NPs was investigated in vivo. It significantly decreased the bacterial burden and increased wound healing percentage compared to the positive control group. Moreover, CuO NPs caused an upregulation of the genes encoding platelet-derived growth factor (PDGF) and fibronectin in tissue repair. Thus, we can use CuO NPs as a future source for wound healing materials, especially in infected wounds.

Celecoxib-Loaded Cubosomal Nanoparticles as a Therapeutic Approach for Staphylococcus aureus In Vivo Infection.

There is a great need for novel approaches to treating bacterial infections, due to the vast dissemination of resistance among pathogenic bacteria. Staphylococcus aureus are ubiquitous Gram-positive pathogenic bacteria and are rapidly acquiring antibiotic resistance. Here, celecoxib was encapsulated into cubosomal nanoparticles, and the particle morphology, size distribution, zeta potential, entrapment efficiency, and celecoxib release were evaluated in vitro. Also, a systemic infection model in mice elucidated the in vivo antibacterial action of the celecoxib cubosomes. Cubosomes are a nanotechnology-based delivery system which can adhere to the external peptidoglycan layers of Gram-positive bacteria and penetrate them. The size distribution investigation revealed that the prepared celecoxib-loaded cubosomes had a mean particle size of 128.15 ± 3.04 nm with a low polydispersity index of 0.235 ± 0.023. The zeta potential measurement showed that the prepared cubosomes had a negative surface charge of -17.50 ± 0.45, indicating a highly stable nanodispersion formation with little susceptibility to particle aggregation. The cubosomal dispersion exhibited an entrapment efficiency of 88.57 ± 2.36%. The transmission electron micrograph for the prepared celecoxib-loaded cubosomes showed a narrow size distribution for the cubosomal nanoparticles, which had a spherical shape and were non-aggregated. The tested cubosomes diminished the inflammation in the treated mice's liver and spleen tissues, as revealed by hematoxylin and eosin stain and Masson's trichrome stain. The immunostained tissues with nuclear factor kappa B and caspase-3 monoclonal antibodies revealed a marked decrease in these markers in the celecoxib-treated group, as it resulted in negative or weak immunostaining in liver and spleen that ranged from 4.54% to 17.43%. This indicates their inhibitory effect on the inflammatory pathway and apoptosis, respectively. Furthermore, they reduced the bacterial burden in the studied tissues. This is alongside a decrease in the inflammatory markers (interleukin-1 beta, interleukin-6, cyclooxygenase-2, and tumor necrosis factor-alpha) determined by ELISA and qRT-PCR. The IL-1ß levels were 16.66 ± 0.5 pg/mg and 17 ± 0.9 pg/mg in liver and spleen, respectively. Also, IL-6 levels were 85 ± 3.2 pg/mg and 84 ± 2.4 pg/mg in liver and spleen, respectively. In conclusion, the current study introduced cubosomes as an approach for the formulation of celecoxib to enhance its in vivo antibacterial action by improving its oral bioavailability.

Protective Role of Betulinic Acid against Cisplatin-Induced Nephrotoxicity and Its Antibacterial Potential toward Uropathogenic Bacteria.

Acute kidney injury (AKI) is one of the major side effects of cisplatin, a remarkable anticancer agent. Therefore, there is a growing need to find an agent that could mitigate cisplatin-induced nephrotoxicity. Betulinic acid (BA) is a natural compound isolated from Silene succulenta Forssk for the first time, with miraculous biological activities and no reports of its effect on the nephrotoxicity induced by cisplatin. Mice received BA orally with doses of 30 and 50 mg/kg before the intraperitoneal injection of cisplatin. Betulinic acid was found to decrease serum levels of creatinine and tissue levels of NGAL and kidney injury molecule (KIM-1) and improve the histological changes in the kidney. In addition, BA decreased the oxidative stress marker malondialdehyde (MDA), increased superoxide dismutase (SOD) antioxidative activity and suppressed the intensity of IL-1B and NFкB immuno-staining. Interestingly, betulinic acid enhanced autophagy by increasing beclin 1, ATG5, and LC3II and decreasing p62 expressions. Thus, our findings suggest betulinic acid as a potential agent that may protect from acute kidney injury by targeting inflammation, oxidative stress, and autophagy processes. Novel drugs are needed to combat the spreading of multidrug resistance between pathogenic bacteria, especially uropathogenic isolates. So, we elucidated the antibacterial properties of BA on Pseudomonas aeruginosa, Escherichia coli, Proteus mirabilis, and Klebsiella pneumoniae. Betulinic acid had minimum inhibitory concentration values (128 to 512 µg/mL). In addition, it adversely affected the membrane integrity of the tested isolates. Accordingly, betulinic acid should be clinically investigated in the future for urinary tract diseases.