Improving plant adaptation to soil antimony contamination: the synergistic contribution of arbuscular mycorrhizal fungus and olive mill waste.

BACKGROUND: This study aimed to investigate the alterations in biochemical and physiological responses of oat plants exposed to antimony (Sb) contamination in soil. Specifically, we evaluated the effectiveness of an arbuscular mycorrhizal fungus (AMF) and olive mill waste (OMW) in mitigating the effects of Sb contamination. The soil was treated with a commercial strain of AMF (Rhizophagus irregularis) and OMW (4% w/w) under two different levels of Sb (0 and 1500 mg kg-1 soil). RESULTS: The combined treatment (OMW + AMF) enhanced the photosynthetic rate (+ 40%) and chlorophyll a (+ 91%) and chlorophyll b (+ 50%) content under Sb condition, which in turn induced more biomass production (+ 67-78%) compared to the contaminated control plants. More photosynthesis in OMW + AMF-treated plants gives a route for phenylalanine amino acid synthesis (+ 69%), which is used as a precursor for the biosynthesis of secondary metabolites, including flavonoids (+ 110%), polyphenols (+ 26%), and anthocyanins (+ 63%) compared to control plants. More activation of phenylalanine ammonia-lyase (+ 38%) and chalcone synthase (+ 26%) enzymes in OMW + AMF-treated plants under Sb stress indicated the activation of phenylpropanoid pathways in antioxidant metabolites biosynthesis. There was also improved shifting of antioxidant enzyme activities in the ASC/GSH and catalytic pathways in plants in response to OMW + AMF and Sb contamination, remarkably reducing oxidative damage markers. CONCLUSIONS: While individual applications of OMW and AMF also demonstrated some degree of plant tolerance induction, the combined presence of AMF with OMW supplementation significantly enhanced plant biomass production and adaptability to oxidative stress induced by soil Sb contamination.

Exploring biosurfactant from Halobacterium jilantaiense as drug against HIV and zika virus: fabrication, characterization, cytosafety property, molecular docking, and molecular dynamics simulation.

Biosurfactants are surface-active molecules with unique qualities and various uses. Many microorganisms produce secondary metabolites with surface-active characteristics that serve various antiviral functions. The HIV and Zika viruses were chosen for this study because they can spread from mother to child and result in potentially fatal infections in infants. Halophilic bacteria from the Red Sea solar saltern in Egypt were screened using drop collapse, emulsification activity, and oil displacement assays to produce biosurfactants and emulsifiers. Halobacterium jilantaiense strain JBS1 was the most effective strain of the Halobacteriaceae family. It had the best oil displacement test and emulsification activity against kerosene and crude oil, respectively. Among the ten isolates, it produced the most promising biosurfactant, also recognized by the GC-MASS library. This study evaluated biosurfactants from halophilic bacteria as potential antiviral drugs. Some of the computer methods we use are molecular docking, ADMET, and molecular dynamics. We use model organisms like the HIV reverse transcriptase (PDB: 5VZ6) and the Zika virus RNA-dependent RNA polymerase (ZV-RdRP). Molecular docking and molecular dynamics make the best complexes with 5VZ6 HIV-RT and flavone (C25) and 5wz3 ZV-RdRP and ethyl cholate (C8). Testing for ADMET toxicity on the complex revealed that it is the safest medicine conceivable. The 5VZ6-C25 and 5wz3-C8 complexes also followed the Lipinski rule. They made five hydrogen bond donors and ten hydrogen bond acceptors with 500 Da MW and a 5:1 octanol/water partition coefficient. Finally, extreme settings require particular adaptations for stability, and extremophile biosurfactants may be more stable.

In vitro and in silico biopotentials of phytochemical compositions and antistaphylococcal and antipseudomonal activities of volatile compounds of Argania spinosa (L.) seed oil.

Active components in medicinal plants provide unlimited useful and traditional medicines. Antimicrobial activities are found in secondary metabolites in plant extracts such as argan oil. This experimental investigation aims to determine argan oil's volatile compounds and examine their in vitro antimicrobial properties. In silico simulations, molecular docking, pharmacokinetics, and drug-likeness prediction revealed the processes underlying the in vitro biological possessions. Gas chromatography-mass spectrometry (GC/MS) was used to screen argan oil's primary components. In silico molecular docking studies were used to investigate the ability of the selected bioactive constituents of argan oil to act effectively against Pseudomonas aeruginosa and Staphylococcus aureus (S. aureus) isolated from infections. The goal was to study their ability to interact with both bacteria's essential therapeutic target protein. The 21 chemicals in argan oil were identified by GC/MS. Docking results for all compounds with S. aureus and P. aeruginosa protease proteins ranged from -5 to -9.4 kcal/mol and -5.7 to -9.7 kcal/mol, respectively, compared to reference ligands. Our docking result indicates that the 10-octadecenoic acid, methyl ester was the most significant compound with affinity scores of -9.4 and -9.7 kcal/mol for S. aureus and P. aeruginosa proteins, respectively. The minimal bactericidal concentration (MBC) and minimal inhibitory concentration (MIC) of argan oil were 0.7 ± 0.03 and 0.5 ± 0.01 for S. aureus and 0.4 ± 0.01 and 0.3 ± 0.02 for P. aeruginosa, respectively. We confirmed the antimicrobial properties of argan oil that showed significant growth inhibition for S. aureus and P. aeruginosa.

Diosgenin alleviates D-galactose-induced oxidative stress in rats' brain and liver targeting aging and apoptotic marker genes.

The theory of aging is primarily concerned with oxidative stress caused by an imbalance in reactive oxygen species generation and cellular antioxidants. To alleviate the oxidative stress, we investigated the protective effect of diosgenin (DSG) for D-galactose (D-gal) using 20 and 40 mg of DSG/kg/day/orally for 42 days. The findings showed that D-gal caused brain and liver oxidative injuries by upregulating aging and oxidative markers. To counteract the oxidative stress caused by D-gal, DSG upregulated glutathione peroxidase-1, superoxide dismutase-1, and glutathione S-transferase-α. DSG also diminished the expression of p53, p21, Bcl-2-associated X protein, caspase-3, and mammalian target of rapamycin in brain and liver, as well as the build-up of ß-galactosidase. DSG, in a dose-dependent manner, decreased the oxidative aging effects of D-gal in brain and liver tissues through targeting of aging and apoptotic marker genes. Finally, it should be noted that consuming DSG supplements is a suggesting natural preventative agent that may counteract aging and preserve health through improvement of body antioxidant status and control aging associated inflammation and cellular apoptosis.

A comprehensive review of discovery and development of drugs discovered from 2020-2022.

To fully evaluate and define the new drug molecule for its pharmacological characteristics and toxicity profile, pre-clinical and clinical studies are conducted as part of the drug research and development process. The average time required for all drug development processes to finish various regulatory evaluations ranges from 11.4 to 13.5 years, and the expense of drug development is rising quickly. The development in the discovery of newer novel treatments is, however, largely due to the growing need for new medications. Methods to identify Hits and discovery of lead compounds along with pre-clinical studies have advanced, and one example is the introduction of computer-aided drug design (CADD), which has greatly shortened the time needed for the drug to go through the drug discovery phases. The pharmaceutical industry will hopefully be able to address the present and future issues and will continue to produce novel molecular entities (NMEs) to satisfy the expanding unmet medical requirements of the patients as the success rate of the drug development processes is increasing. Several heterocyclic moieties have been developed and tested against many targets and proved to be very effective. In-depth discussion of the drug design approaches of newly found drugs from 2020 to 2022, including their pharmacokinetic and pharmacodynamic profiles and in-vitro and in-vivo assessments, is the main goal of this review. Considering the many stages these drugs are going through in their clinical trials, this investigation is especially pertinent. It should be noted that synthetic strategies are not discussed in this review; instead, they will be in a future publication.

Nanoformulated 3'-diindolylmethane modulates apoptosis, migration, and angiogenesis in breast cancer cells.

Background: It is well-established that specific herbal plants contain natural active ingredients that have demonstrated anti-cancer potential. Therefore, they are considered highly beneficial as a potential adjuvant, alternative or complementary agent in anti-cancer therapy. However, the low chemical stability and limited bioavailability of 3, 3'-Diindolylmethane (DIM), a plant-derived compound used in clinical settings, limit its therapeutic applications. To overcome this challenge, researchers have focused on developing innovative approaches to improve DIM's biological activity, such as utilizing nanoformulations. Here, we investigated the potential benefits of coating DIM nanoparticles (DIM-NPs) with PEG/chitosan in the treatment of breast cancer. Our results demonstrate the molecular mechanism underlying the activity of DIM-NPs, highlighting their potential as an effective therapeutic strategy for breast cancer treatment. Methods: DIM-PLGA-PEG/chitosan NPs were synthesised and characterised using dynamic light scattering (DLS) and evaluated the impact of these NPs on two breast cancer cell models. Results: DIM-NPs had an average diameter of 102.3 nm and a PDI of 0.182. When treated with DIM-NPs for 48 h, both MCF7 and MDA-MB-231 cells displayed cytotoxicity at a concentration of 6.25 g/mL compared to untreated cells. Furthermore, in MDA-MB-231 cells, treatment with 2.5 µg/mL of DIM-NPs resulted in a significant decrease in cell migration, propagation, and angiogenesis which was further enhanced at 10 µg/mL. In chicken embryos, treatment with 5 µg/mL of DIM-NPs on day 2 led to a significant reduction in angiogenesis. Furthermore, this treatment induced cell death through a regulatory pathway involving the upregulation of Bax and p53, as well as the downregulation of Bcl-2. These results were supported by in-silico analysis of DIM's binding affinity to key proteins involved in this pathway, namely Bax, Bcl-2, and p53. Conclusion: Our findings show that DIM-NPs induces apoptosis, inhibit migration, and reduce angiogenesis in breast cancer. However, further research using a preclinical cancer model may be necessary to determine the pharmacokinetics of DIM-NPs and ensure their safety and efficacy in vivo.

Chromium(VI) Toxicity and Active Tolerance Mechanisms of Wheat Plant Treated with Plant Growth-Promoting Actinobacteria and Olive Solid Waste.

The present study aimed to assess the potential of plant growth-promoting Actinobacteria and olive solid waste (OSW) in ameliorating some biochemical and molecular parameters of wheat (Triticum aestivum) plants under the toxicity of high chromium levels in the soil. With this aim, a pot experiment was conducted, where the wheat plants were treated with a consortium of four Actinobacterium sp. (Bf treatment) and/or OSW (4% w/w) under two levels of nonstress and chromium stress [400 mg Cr(VI) per kg of soil] to estimate the photosynthetic traits, antioxidant protection machine, and detoxification activity. Both Bf and OSW treatments improved the levels of chlorophyll a (+47-98%), carotenoid (+324-566%), stomatal conductance (+17-18%), chlorophyll fluorescence (+12-28%), and photorespiratory metabolism (including +44-72% in glycolate oxidase activity, +6-72% in hydroxypyruvate reductase activity, and +5-44% in a glycine to serine ratio) in leaves of stressed plants as compared to those in the stressed control, which resulted in higher photosynthesis capacity (+18-40%) in chromium-stressed plants. These results were associated with an enhancement in the content of antioxidant metabolites (+10-117%), of direct reactive oxygen species-detoxifying enzymes (+49-94%), and of enzymatic (+40-261%) and nonenzymatic (+17-175%) components of the ascorbate-glutathione cycle in Bf- and OSW-treated plants under stress. Moreover, increments in the content of phytochelatins (+38-74%) and metallothioneins (+29-41%), as markers of detoxification activity, were recorded in the plants treated with Bf and OSW under chromium toxicity. In conclusion, this study revealed that the application of beneficial Actinobacteria and OSW as biofertilization/supplementation could represent a worthwhile consequence in improving dry matter production and enhancing plant tolerance and adaptability to chromium toxicity.

Apocynin attenuates methotrexate-induced mucositis by regulating NF-κB, PPAR-γ and Bax/Bcl-2/Puma signals.

Oxidative stress, inflammation and apoptosis are the primary inducers of Methotrexate (MTX)-induced mucositis. This research aimed to determine whether apocynin (APO) could protect against MTX-induced mucositis. The antioxidants, anti-inflammatory and anti-apoptotic actions of APO in this model will be evaluated. The experiment was performed on 32 rats. A single dose (20 mg/kg) of MTX was injected i.p. to induce intestinal mucositis. APO was given orally once per day at a dose of 100mg/kg (five days prior to and five days following an MTX injection). APO safeguarded the histological structure of the duodenal mucosa, as observed by the conserved histology of goblet cells (villi and crypts). APO mitigated oxidative stress by reducing intestin MDA and raising GSH, SOD and GST, also suppressing NF-κB mRNA expression. Intestinal content of proinflammatory cytokines was reduced in APO-treated MTX rats, with downregulation of proinflammatory iNOS and upregulation of anti-inflammatory PPAR-γ proteins. The intestinal mucosa of rats treated with APO and MTX displayed weekly positive immune staining for cleaved caspase-3. APO upregulate the anti-apoptotic Bcl2 mRNA and down regulate the proapoptotic Bax and Puma mRNA in the duodenal mucosa. The results indicate the possibility of using APO as a novel therapeutic agent to prevent MTX-induced mucositis.

Staphylococcus aureus Induced Wound Infections Which Antimicrobial Resistance, Methicillin- and Vancomycin-Resistant: Assessment of Emergence and Cross Sectional Study.

Background: Wound infection is a prevalent concern in the medical field, being is a multi-step process involving several biological processes. Methicillin-resistant S. aureus (MRSA) and vancomycin-resistant S. aureus (VRSA) infections often occur in areas of damaged skin, such as abrasions and open wounds. Methods: This research aims to light the incidence of MRSA and VRSA in wound swabs, the antimicrobial susceptibility configuration of isolated S. aureus patterns in pus/wound samples collected from Saudi Arabian tertiary hospital. The cross section study, ß- lactamase detection, VRSA genotyping, MAR index, D-test and VRSA genotyping are methods, which used for completed this research. Results: Patients of several ages and genders delivered specimens from two hospitals in the Al jouf area, in the northern province of Saudi Arabia. S. aureus was found in 188 (34.7%) of the 542 wounds. The traumatized wounds provided 71 isolates (38.8%), surgical wound provided 49 isolates (26.8%) and abscess were represented 16 by isolates (8.7%). In the study, 123 (65.4%) out of 188 were MRSA, 60 (31.9%) were MSSA, and five (2.7%) were VRSA. Linezolid and rifampin were found to be the most effective antimicrobials with 100% in vitro antibacterial activity against S. aureus isolates. The Multiple antimicrobials resistance (MAR) index revealed 73 isolates (38.9%) with a MAR index greater than 0.2, and 115 (61.1%) less than 0.2. The D-test showed that of MLSb phenotypes among S. aureus, 22 (11.7%) strains were D-test positive (MLSbi phenotype), 53 (28.2%) strains were constitutive MLSc phenotypes, and 17 (9%) strains were shown to have MSb phenotypes. All VRSA isolates (n=5) were found to be positive for vanA, and no vanB positive isolates were detected in the study. Conclusion: Regular monitoring and an antimicrobials stewardship program should be in place to provide critical information that can be utilized for empirical therapy and future prevention strategies.

Apoptosis induction in human hepatoma cell line HepG2 cells by trans- Anethole via activation of mitochondria-mediated apoptotic pathways.

trans-Anethole a valuable compound derived from star anise widely used by ethnic tribals to manage numerous human diseases. In this study antiproliferative activities of trans-Anethole towards human liver cancer (HepG2), cervical cancer (HeLa) and breast cancer (MCF-7) cells were explored. trans-Anethole showed free radical scavenging potential as assessed by DNA nicking assay. trans-Anethole exhibited strong antiproliferative potential towards HepG2 cells compared to other cell lines. trans-Anethole strongly induced apoptosis in HepG2 cells by significantly upregulating the protein expressions of p53, Caspase-3 and Caspase-9 were assessed by western blotting analysis which highlighted apoptosis-inducing capacity of trans-Anethole against HepG2 cells. Rt-qPCR analysis revealed that trans- Anethole upregulated p53, caspase - 3 and - 9 in comparison to untreated HepG2 cancer cells. Moreover, trans-Anethole provoked the generation of ROS and disruption of MMP. Our research suggests that trans-Anethole may have a significant anticancer therapeutic potential for treating liver cancer.

Novel curcumin nanoformulation induces apoptosis, and reduces migration and angiogenesis in liver cancer cells.

BACKGROUND: Curcumin has been used in the treatment of several diseases; however, its low pharmacologic profile reduces its therapeutic use. Towards improving its biological activity, nanoformulations have emerged. Thus, we aimed to determine whether curcumin nanoparticles (Cur-NPs) coated with PEG/chitosan improve the treatment of liver cancer (LC) cells and underpin the molecular mechanisms underlying their anti-cancer activity. METHODS: Cur-NPs were synthesised in the form of Cur-PLGA-PEG/chitosan NPs. The effect of Cur-NPs was assessed in HepG2 and Huh 7 LC cells and THLE-2 normal liver cells. RESULTS: The size of synthesised Cur-NPS was determined in the standard range of 141.2 ± 47.5 nm. Compared to THLE-2 cells, LC cells treated with Cur-NPs exerted cytotoxicity at 6.25 µg/mL after 48h. Treatment of HepG-2 cells with 2.5 µg/mL of Cur-NPs inhibited cell migration and this inhibition was augmented at 10 µg/mL (p < 0.001). Treatment of chicken embryo with 5 µg/mL Cur-NPs reduced angiogenesis (p < 0.001) of 4-day-old embryos. The nanoformulation upregulated Bax and p53 and downregulated Bcl-2 in a concentration-dependent manner and subsequently induce apoptosis in HepG-2 cells. CONCLUSION: Treatment of LC cells with Cur-NPs decreased cell proliferation, migration, and angiogenesis, and induced cell death by promoting the proapoptotic pathway.

Curcumin nanoparticles (Cur-NPs) increase the anticancer efficiency of Curcumin against liver cancer cells.Cur-NPs induce apoptotic cell death of Liver cancer cells.Cur-NPs have ant-angiogenesis and metastasis effect.

Dietary Olive Leaf Extract Differentially Modulates Antioxidant Defense of Normal and Aeromonas hydrophila-Infected Common Carp (Cyprinus carpio) via Keap1/Nrf2 Pathway Signaling: A Phytochemical and Biological Link.

Olive leaves are an immense source of antioxidant and antimicrobial bioactive constituents. This study investigated the effects of dietary incorporation of olive leaf extract (OLE) on the growth performance, hematobiochemical parameters, immune response, antioxidant defense, histopathological changes, and some growth- and immune-related genes in the common carp (Cyprinus carpio). A total of 180 fish were allocated into four groups with triplicate each. The control group received the basal diet without OLE, while the other three groups were fed a basal diet with the OLE at 0.1, 0.2, and 0.3%, respectively. The feeding study lasted for 8 weeks, then fish were challenged with Aeromonas hydrophila. The results revealed that the group supplied with the 0.1% OLE significantly exhibited a higher final body weight (FBW), weight gain (WG%), and specific growth rate (SGR) with a decreased feed conversion ratio (FCR) compared to the other groups (p < 0.05). An increase in immune response was also observed in the fish from this group, with higher lysosome activity, immunoglobulin (IgM), and respiratory burst than nonsupplemented fish, both before and after the A. hydrophila challenge (p < 0.05). Similarly, the supplementation of the 0.1% OLE also promoted the C. carpio's digestive capacity pre- and post-challenge, presenting the highest activity of protease and alkaline phosphatase (p < 0.05). In addition, this dose of the OLE enhanced fish antioxidant capacity through an increase in the activity of superoxide dismutase (SOD) and glutathione peroxidase (GPx) and decreased hepatic lipid peroxidation end products (malondialdehyde-MDA), when compared to the control group, both pre- and post-infection (p < 0.05). Concomitantly with the superior immune response and antioxidant capacity, the fish fed the 0.1% OLE revealed the highest survival rate after the challenge with A. hydrophila (p < 0.05). A significant remarkable upregulation of the hepatic sod, nrf2, and protein kinase C transcription levels was detected as a vital approach for the prevention of both oxidative stress and inflammation compared to the infected unsupplied control group (p < 0.05). Interestingly, HPLC and UPLC-ESI-MS/MS analyses recognized that oleuropein is the main constituent (20.4%) with other 45 compounds in addition to tentative identification of two new compounds, namely oleuroside-10-carboxylic acid (I) and demethyl oleuroside-10-carboxylic acid (II). These constituents may be responsible for the OLE exerted potential effects. To conclude, the OLE at a dose range of 0.66-0.83 g/kg w/w can be included in the C. carpio diet to improve the growth, antioxidant capacity, and immune response under normal health conditions along with regulating the infection-associated pro-inflammatory gene expressions, thus enhancing resistance against A. hydrophila.

Molecular Profile and the Effectiveness of Antimicrobials Drugs Against Staphylococcus aureus and Pseudomonas aeruginosa in the Diagnostic Approaches of Otitis Infection.

Background: Otitis externa and otitis media are two types of ear infections that affect people of all ages, although they are more common in newborns and young children. Antibiotic usage, healthcare, and advanced age all play a role in the development of this illness. Methods: Fifty-eight patients with various kinds of infections of the ears were voluntary patients attending the outpatient clinics of the Prince Mutaib Bin Abdulaziz Hospital in Sakaka, Al Jouf, Saudi Arabia, examined to evaluate the role of bacteria and the likely significance of plasmids in their antibiotic resistance as ear infectious agents. Results: Staphylococcus aureus and Pseudomonas aeruginosa are the most prevalent bacteria found in ear infections. The greatest number of major bacterial isolates were S. aureus (54%), followed by P. aeruginosa (13%), whereas a smaller number of isolates (3%) were from Streptococcus pyogenes, Bacillus subtilis, and Proteus vulgaris, respectively. Mixed growth was noted in 3.4% of instances. The isolation rate for Gram-positive organisms was 72%, while the rate for Gram-negative species was 28%. All the isolates had DNA greater than 14 kilobases. Hind III analysis of the plasmid DNA extracted from the resistant strains of ear infection demonstrated that antibiotic-resistance plasmids were extensively dispersed. Exotoxin A PCR amplification indicated 396 pb PCR-positive DNA for all identified samples, with the exception of three strains for which no band was observed. Patients in the epidemiological study ranged in number, but all were linked together for the purposes of the study because of their shared epidemiological characteristics. Conclusion: Vancomycin, linezolid, tigecycline, rifampin, and daptomycin are all antibiotics that have been shown to be effective against S. aureus and P. aeruginosa. Microbiological pattern evaluation and antibiotic sensitivity patterns of the microorganisms providing empirical antibiotics are becoming increasingly crucial to minimize issues and the development of antibiotic-resistant strains.

Ameliorative avian gut environment and bird productivity through the application of safe antibiotics alternatives: a comprehensive review.

The avian digestive tract is an important system for converting ingested food into the nutrients their bodies need for maintenance, growth, and reproduction (meat, table eggs, and fertile eggs). Therefore, preserving digestive system integrity is crucial to bird health and productivity. As an alternative to antibiotics, the world has recently turned to the use of natural products to enhance avian development, intestinal health, and production. Therefore, the primary goal of this review is to explain the various characteristics of the avian digestive tract and how to enhance its performance with natural, safe feed additives such as exogenous enzymes, organic acids, photogenic products, amino acids, prebiotics, probiotics, synbiotics, and herbal extracts. In conclusion, the composition of the gut microbiome can be influenced by a number of circumstances, and this has important consequences for the health and productivity of birds. To better understand the connection between pathogens, the variety of therapies available, and the microbiome of the gut, additional research needs to be carried out.

Avian campylobacteriosis, prevalence, sources, hazards, antibiotic resistance, poultry meat contamination, and control measures: a comprehensive review.

Avian campylobacteriosis is a vandal infection that poses human health hazards. Campylobacter is usually colonized in the avian gut revealing mild signs in the infected birds, but retail chicken carcasses have high contamination levels of Campylobacter spp. Consequently, the contaminated avian products constitute the main source of human infection with campylobacteriosis and result in severe clinical symptoms such as diarrhea, abdominal pain, spasm, and deaths in sensitive cases. Thus, the current review aims to shed light on the prevalence of Campylobacter in broiler chickens, Campylobacter colonization, bird immunity against Campylobacter, sources of poultry infection, antibiotic resistance, poultry meat contamination, human health hazard, and the use of standard antimicrobial technology during the chicken processing of possible control strategies to overcome such problems.

Rutin attenuates D-galactose-induced oxidative stress in rats' brain and liver: molecular docking and experimental approaches.

Oxidative stress results from the imbalance between reactive oxygen species (ROS) production and antioxidant defence and is primarily involved in aging. The current study investigated the antioxidant activity of rutin in aging in rats induced by D-galactose (D-gal) for 42 days. Rutin was orally used at doses of 50 and 100 mg kg-1 daily. Results showed that D-gal induced oxidative alterations in the brain and liver recognized via upregulation of aging and oxidative markers. In contrast, rutin ameliorated the oxidative stress induced by D-gal by enhancing antioxidant markers such as superoxide dismutase-1, glutathione peroxidase-1, and glutathione S-transferase-α. Also, rutin significantly decreased the accumulation of ß-galactosidase and reduced the expression of p53, p21, Bcl-2-associated X protein (Bax), caspase-3 (CASP3), and mammalian target of rapamycin (mTOR) in brain and hepatic tissues. Rutin potentially attenuated these aging-related oxidative alterations in a dose-dependent manner. Moreover, rutin markedly reduced the increased immunohistochemical expression of ß-galactosidase, 8-hydroxy-2'-deoxyguanosine, calcium-binding adapter molecule 1, glial fibrillary acidic protein, Bax, and interleukin-6 and significantly increased Bcl2, synaptophysin, and Ki67. Furthermore, a molecular docking study revealed that rutin exhibited high affinity to rat and human caspases, PI3K/AKT/mTOR, and the IL-6 receptor. Finally, we can conclude that rutin supplementation can be a promising natural protective compound that could delay aging and maintain health.

Characterization of Delonix regia Flowers' Pigment and Polysaccharides: Evaluating Their Antibacterial, Anticancer, and Antioxidant Activities and Their Application as a Natural Colorant and Sweetener in Beverages.

In the present study, an attempt was made to investigate the in vitro antioxidant, anticancer, and antibacterial activities of Delonix regia, then in vivo evaluate its safety as a natural colorant and sweetener in beverages compared to synthetic colorant and sweetener in rats, then serve the beverages for sensory evaluation. Delonix regia flowers had high protein, polysaccharide, Ca, Na, Mg, K, and Fe contents. The Delonix regia pigment extract (DRPE) polysaccharides were separated and purified by gel permeation chromatography on Sephacryl S-200, characterized by rich polysaccharides (13.6 g/L). The HPLC sugar profile detected the monosaccharides in the extracted polysaccharides, composed of mannose, galactose, glucose, arabinose, and gluconic acid, and the structure of saccharides was confirmed by FTIR, which showed three active groups: carbonyl, hydrocarbon, and hydroxyl. On the other hand, the red pigment constituents of DRPE were detected by HPLC; the main compounds were delphinidin and cyanidin at 15 µg/mL. The DRPE contained a considerable amount (26.33 mg/g) of anthocyanins, phenolic compounds (64.7 mg/g), and flavonoids (10.30 mg/g), thus influencing the antioxidant activity of the DRPE, which scavenged 92% of DPPH free radicals. Additionally, it inhibited the population of pathogenic bacteria, including Staphylococcus aureus, Listeria monocyogenes, Salmonella typhimurum, and Pseudomonas aeruginosa, in the range of 30-90 µg/mL, in addition to inhibiting 85% of pancreatic cancer cell lines. On the in vivo level, the rats that were delivered a diet containing DRPE showed regular liver markers (AST, ALP, and ALT); kidney markers (urea and creatinine); high TP, TA, and GSH; and low MDA, while rats treated with synthetic dye and aspartame showed higher liver and kidney markers; lowered TP, TA, and GSH; and high MDA. After proving the safety of DRPE, it can be safely added to strawberry beverages. Significant sensorial traits, enhanced red color, and taste characterize the strawberry beverages supplemented with DRPE. The lightness and redness of strawberries were enhanced, and the color change ΔE values in DRPE-supplemented beverages ranged from 1.1 to 1.35 compared to 1.69 in controls, indicating the preservative role of DRPE on color. So, including DRPE in food formulation as a natural colorant and sweetener is recommended for preserving health and the environment.

Antimicrobial Resistance Pattern, Pathogenicity and Molecular Properties of Hypervirulent Klebsiella pneumonia (hvKp) among Hospital-Acquired Infections in the Intensive Care Unit (ICU).

Hypervirulent Klebsiella pneumoniae (hvKp) is a new emerging variant of K. pneumoniae that is increasingly reported worldwide. The variant hvKp is known to cause severe invasive community-acquired infections such as metastatic meningitis, pyogenic liver abscesses (PLA) and endophthalmitis, but its role in hospital-acquired infections (HAIs) is little known. The aim of this study was to evaluate the prevalence of hvKp among hospital-acquired (HA) K. pneumoniae infections in the intensive care unit (ICU) and to compare between hvKp and classical K. pneumoniae (cKP) regarding antimicrobial resistance pattern, virulence and molecular characteristics. The study was cross-sectional and included 120 ICU patients suffering from HA K. pneumoniae infections between January and September 2022. K. pneumoniae isolates were subjected to antimicrobial susceptibility testing and detection of extended-spectrum-ß-lactamase (ESBL) production by the Phoenix 100 automated microbiology system, string test, biofilm formation, serum resistance assay, and detection of virulence-associated genes (rmpA, rmpA2, magA, iucA) and capsular serotype-specific genes (K1, K2, K5, K20, K57) by polymerase chain reaction (PCR). Of 120 K. pneumoniae isolates, 19 (15.8%) were hvKp. The hypermucoviscous phenotype was more significantly detected in the hvKp group than in the cKP group (100% vs. 7.9%, p ≤ 0.001). The rate of resistance to different antimicrobial agents was significantly higher in the cKP group than that in the hvKp group. Fifty-three strains were identified as ESBL-producing strains, which was more frequent in the cKP group than in the hvKp group (48/101 [47.5%] vs. 5/19 [26.3%], respectively, p ≤ 0.001). The hvKP isolates were highly associated with moderate and strong biofilm formation than cKP isolates (p = 0.018 and p = 0.043 respectively). Moreover, the hvKP isolates were highly associated with intermediate sensitivity and re sistance to serum in the serum resistance assay (p = 0.043 and p = 0.016 respectively). K1, K2, rmpA, rmpA2, magA and iucA genes were significantly associated with hvKp (p ≤ 0.001, 0.004, <0.001, <0.001, 0.037 and <0.001, respectively). However, K5, K20 and K57 were not associated with hvKp. The hvKp strains have emerged as a new threat to ICU patients because of their ability to cause more severe and life-threatening infections than cKP. The string test alone as a laboratory test for screening of hvKp has become insufficient. Recently, hvKp was defined as hypermucoviscous- and aerobactin-positive. It is important to improve the awareness towards the diagnosis and management of hvKp infections.

Natural bioactive compounds-doxorubicin combinations targeting topoisomerase II-alpha: Anticancer efficacy and safety.

Cancer is one of the leading causes of death worldwide, so pursuing effective and safe therapeutics for cancer is a key research objective nowadays. Doxorubicin (DOX) is one of the commonly prescribed chemotherapeutic agents that has been used to treat cancer with its antimitotic properties via inhibition of topoisomerase II (TOP2) activity. However, many problems hinder the broad use of DOX in clinical practice, including cardiotoxicity and drug resistance. Research in drug discovery has confirmed that natural bioactive compounds (NBACs) display a wide range of biological activities correlating to anticancer outcomes. The combination of NBACs has been seen to be an ideal candidate that might increase the effectiveness of DOX therapy and decreases its unfavorable adverse consequences. The current review discusses the chemo-modulatory mechanism and the protective effects of combined DOX with NBACs with a binding affinity (pKi) toward TOP2A more than pKi of DOX. This review will also discuss and emphasize the molecular mechanisms to provide a pathway for further studies to reveal other signaling pathways. Taken together, understanding the fundamental mechanisms and implications of combined therapy may provide a practical approach to battling cancer diseases.

Pomegranate Peel Extract Stabilized Selenium Nanoparticles Synthesis: Promising Antimicrobial Potential, Antioxidant Activity, Biocompatibility, and Hemocompatibility.

The green synthesis of selenium nanoparticles (Se NPs) had been synthesized by pomegranate peel extract (PPE). The antimicrobial, antioxidant, and anticancer activities of the synthesized Se NPs, as well as their hemocompatibility, were investigated. Se NPs were characterized by UV-Vis., SEM, XRD, HR-TEM, DLS, EDX, FTIR, and mapping techniques. HR-TEM image represented the spheroidal forms with moderately monodispersed NPs with a mean diameter 14.5 nm. The SEM image of Se NPs, incorporated with PPE, exhibits uniform NP surfaces, and the appearance was clear. The antimicrobial results confirmed the potential of Se NPs to hinder the growth of some tested pathogenic microbes. Results revealed that Se NPs exhibited promising antibacterial activity against Escherichia coli, Pseudomonas aeruginosa, Bacillus subtilis, Staphylococcus aureus, and Streptococcus mutans where inhibition zones were 29, 16, 41, 22, and 54 mm, respectively. Likewise, it exhibited antifungal activity where the values of inhibition zones were 41, 40, 38, and 36 mm against Candida albicans, Cryptococcus neoformans, Aspergillus fumigatus, and A. niger, respectively. The antioxidant activities of Se NPs at concentrations 250-4000 µg/mL were greater than 90% in all cases. Se NP concentrations of 500 µg/mL or less are safe in usage according to hemocompatibility study. Se NPs had an IC50 of 113.73 µg/mL in a cytotoxicity experiment. Results revealed that Se NPs have promising anticancer activities against MCF7 and Mg63 cancerous cell line, where IC50 was 69.8 and 47.9 µg/mL, respectively. In conclusion, Se NPs were successfully biosynthesized using PPE for the first time; these Se NPs had promising antimicrobial, antioxidant, and anticancer activities.