Synergistic effects of quercetin-loaded CoFe2O4@Liposomes regulate DNA damage and apoptosis in MCF-7 cancer cells: based on biophysical magnetic hyperthermia.

INTRODUCTION: Breast cancer (BC) is the most common malignancy in women globally. Significant progress has been made in developing structural nanoparticles (NPs) and formulations for targeted smart drug delivery (SDD) of pharmaceuticals, improving the precision of tumor cell targeting in therapy.Significance: Magnetic hyperthermia (MHT) treatment using magneto-liposomes (MLs) has emerged as a promising adjuvant cancer therapy. METHODS: CoFe2O4 magnetic NPs (MNPs) were conjugated with nanoliposomes to form MLs, and the anticancer drug quercetin (Que) was loaded into MLs, forming Que-MLs composites for antitumor approach. The aim was to prepare Que-MLs for DD systems (DDS) under an alternating magnetic field (AMF), termed chemotherapy/hyperthermia (chemo-HT) techniques. The encapsulation efficiency (EE), drug loading capacity (DL), and drug release (DR) of Que and Que-MLs were evaluated. RESULTS: The results confirmed successful Que-loading on the surface of MLs, with an average diameter of 38nm and efficient encapsulation into MLs (69%). In vitro, experimental results on MCF-7 breast cells using MHT showed high cytotoxic effects of novel Que-MLs on MCF-7 cells. Various analyses, including cytotoxicity, apoptosis, cell migration, western blotting, fluorescence imaging, and cell membrane internalization, were conducted. The Acridine Orange-ethidium bromide double fluorescence test identified 35% early and 55% late apoptosis resulting from Que-MLs under the chemo-HT group. TEM results indicated MCF-7 cell membrane internalization and digestion of Que-MLs, suggesting the presence of early endosome-like vesicles on the cytoplasmic periphery. CONCLUSIONS: Que-MLs exhibited multi-modal chemo-HT effects, displaying high toxicity against MCF-7 BC cells and showing promise as a potent cytotoxic agent for BC chemotherapy.

Emerging Perspectives on the Impact of Diabetes Mellitus and Anti-Diabetic Drugs on Premenstrual Syndrome. A Narrative Review.

Diabetes mellitus (DM) and premenstrual syndrome (PMS) are global health challenges. Both disorders are often linked to a range of physical and psychological symptoms that significantly impact the quality of life of many women. Yet, the exact relation between DM and PMS is not clear, and the management of both conditions poses a considerable challenge. In this review, we aimed to investigate the interplay between DM, anti-diabetic drugs, and the different theories and symptoms of PMS. Female sex hormones are implicated in the pathophysiology of PMS and can also impair blood glucose control. In addition, patients with diabetes face a higher susceptibility to anxiety and depression disorders, with a significant number of patients experiencing symptoms such as fatigue and difficulty concentrating, which are reported in patients with PMS as well. Complications related to diabetic medications, such as hypoglycemia (with sulfonylurea) and fluid retention (with thiazolidinediones) may also mediate PMS-like symptoms. DM can, in addition, disturb the normal gut microbiota (GM), with a consequent loss of beneficial GM metabolites that guard against PMS, particularly the short-chain fatty acids and serotonin. Among the several available anti-diabetic drugs, those (1) with an anti-inflammatory potential, (2) that can preserve the beneficial GM, and (3) possessing a lower risk for hypoglycemia, might have a favorable outcome in PMS women. Yet, well-designed clinical trials are needed to investigate the anti-diabetic drug(s) of choice for patients with diabetes and PMS.

A Systematic Review of Novel Therapies of Pulmonary Arterial Hypertension.

BACKGROUND: Pulmonary arterial hypertension (PAH) is a progressive, cureless disease, characterized by increased pulmonary vascular resistance and remodeling, with subsequent ventricular dilatation and failure. New therapeutic targets are being investigated for their potential roles in improving PAH patients' symptoms and reversing pulmonary vascular pathology. METHOD: We aimed to address the available knowledge from the published randomized controlled trials (RCTs) regarding the role of Rho-kinase (ROCK) inhibitors, bone morphogenetic protein 2 (BMP2) inhibitors, estrogen inhibitors, and AMP-activated protein kinase (AMPK) activators on the PAH evaluation parameters. This systematic review (SR) was registered in the International Prospective Register of Systematic Reviews (PROSPERO) database (CDR42022340658) and followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. RESULTS: Overall, 5092 records were screened from different database and registries; 8 RCTs that met our inclusion criteria were included. The marked difference in the study designs and the variability of the selected outcome measurement tools among the studies made performing a meta-analysis impossible. However, the main findings of this SR relate to the powerful potential of the AMPK activator and the imminent antidiabetic drug metformin, and the BMP2 inhibitor sotatercept as promising PAH-modifying therapies. There is a need for long-term studies to evaluate the effect of the ROCK inhibitor fasudil and the estrogen aromatase inhibitor anastrozole in PAH patients. The role of tacrolimus in PAH is questionable. The discrepancy in the hemodynamic and clinical parameters necessitates defining cut values to predict improvement. The differences in the PAH etiologies render the judgment of the therapeutic potential of the tested drugs challenging. CONCLUSION: Metformin and sotatercept appear as promising therapeutic drugs for PAH. CLINICAL TRIALS REGISTRATION: This work was registered in PROSPERO (CDR42022340658).

Investigation of Antifungal Action of Fractions C17H31NO15 Isolated from Artemisia herba-alba extract versus Isolated Aspergillus niger from Zee maize.

BACKGROUND: Plants are harmed by parasitic organisms, and toxic poisons are created. Phytopathogenic fungi create toxins that can severely harm plants' basic physiological functioning. OBJECTIVE: Investigation of antifungal impact of various fractions of methanol extract of Artemisia herba-alba to Aspergillus niger as a plant pathogen. METHODS: Artemisia herba-alba extract was purified using column chromatography, giving various antifungal fractions tested versus A. niger. RESULTS: The 6th fraction give the highest inhibition zone with a diameter of 5.4 cm and MIC 125.02 ± 4.9 µg/ml, which was identified using Mass spectroscopy, 1HNMR, Elemental analysis as well as IR testing, revealing the chemical formula of the purified fraction. Ultrastructure alteration of treated A. niger was examined versus control using the transmission electron microscope. Purified fraction has tested versus normal cell line with minimal cytotoxicity. CONCLUSION: These results revealed the possibility of using Artemisia herba-alba methanol extract as a promising antifungal versus phytopathogenic fungi, especially A. niger after more verification of results.

Investigation of the potential roles of adipose stem cells and substances of natural origin in the healing process of E. coli infected wound model in Rats.

Skin infections by pathogenic microorganisms are a serious problem due to the potential of dissemination through the bloodstream to various organs causing toxic effects that may be up to mortality. Escherichia coli (E. coli) is one of the most predominant Gram-negative bacterial species present globally with great attention for investigation. The current study is designed to investigate the possible role of adipose tissue-derived stem cells (ADSCs), as well as natural products such as Trichoderma viride (T. viride) extract, Saccharomyces boulardii (S. boulardii) solution in the enhancement of wound healing process in the infected skin with E. coli. Ninety-six female rats were divided into 8 groups (12 animal/group): normal skin, wounded skin, wounded skin infected with E. coli, infected-wounded skin treated by ADSCs, infected-wounded skin treated by T. viride extract, infected-wounded skin treated by S. boulardii solution, infected-wounded skin treated a combination of treatments, infected-wounded skin treated by gentamicin. At day 21 animal weights and bacterial count were detected and compared. Animals were sacrificed and skin from various groups was investigated using a light microscope for sections stained by (hematoxylin eosin, Masson trichrome, and PCNA) as well as transmission electron microscopy. Pro-inflammatory (IL-1ß, TNF- α, and IL-13), anti-inflammatory cytokine (IL-4), and antioxidant enzymes (Superoxide dismutase, glutathione, and catalase) were assessed in various groups revealing that ADSCs lightly shift levels of these parameters in various rat groups to regular levels, while administration of T. viride extract, S. boulardii solution, their combination with ADSCs and gentamicin treatment drive the tested cytokines and enzymes to significant levels similar to a normal level where combination therapy gave the best result. The current findings revealed the possibility of using certain natural products as possible substitutes to regularly applied antibiotics with successive protective results in the wound infection model.

Surf Redfish-Based ZnO-NPs and Their Biological Activity with Reference to Their Non-Target Toxicity.

The marine environment is a rich source of bioactive compounds. Therefore, the sea cucumber was isolated from the Red Sea at the Al-Ain Al-Sokhna coast and it was identified as surf redfish (Actinopyga mauritiana). The aqueous extract of the surf redfish was utilized as an ecofriendly, novel and sustainable approach to fabricate zinc oxide nanoparticles (ZnO-NPs). The biosynthesized ZnO-NPs were physico-chemically characterized and evaluated for their possible antibacterial and insecticidal activities. Additionally, their safety in the non-target organism model (Nile tilapia fish) was also investigated. ZnO-NPs were spherical with an average size of 24.69 ± 11.61 nm and had a peak at 350 nm as shown by TEM and UV-Vis, respectively. XRD analysis indicated a crystalline phase of ZnO-NPs with an average size of 21.7 nm. The FTIR pattern showed biological residues from the surf redfish extract, highlighting their potential role in the biosynthesis process. DLS indicated a negative zeta potential (-19.2 mV) of the ZnO-NPs which is a good preliminary indicator for their stability. ZnO-NPs showed larvicidal activity against mosquito Culex pipiens (LC50 = 15.412 ppm and LC90 = 52.745 ppm) and a potent adulticidal effect to the housefly Musca domestica (LD50 = 21.132 ppm and LD90 = 84.930 ppm). Tested concentrations of ZnO-NPs showed strong activity against the 3rd larval instar. Topical assays revealed dose-dependent adulticidal activity against M. domestica after 24 h of treatment with ZnO-NPs. ZnO-NPs presented a wide antibacterial activity against two fish-pathogen bacteria, Pseudomonas aeruginosa and Aeromonas hydrophila. Histopathological and hematological investigations of the non-target organism, Nile tilapia fish exposed to 75-600 ppm ZnO-NPs provide dose-dependent impacts. Overall, data highlighted the potential applications of surf redfish-mediated ZnO-NPs as an effective and safe way to control mosquitoes, houseflies and fish pathogenic bacteria.

GC-MS Analysis, Antibacterial, and Anticancer Activities of Hibiscus sabdariffa L. Methanolic Extract: In Vitro and In Silico Studies.

The emergence of bacteria that are resistant to several antibiotics has represented a serious hazard to human health globally. Bioactive metabolites from medicinal plants have a wide spectrum of therapeutic possibilities against resistant bacteria. Therefore, this study was performed to investigate the antibacterial efficacy of various extracts of three medicinal plants as Salvia officinalis L., Ziziphus spina-christi L., and Hibiscus sabdariffa L. against pathogenic Gram-negative Enterobacter cloacae (ATCC13047), Pseudomonas aeruginosa (RCMB008001), Escherichia coli (RCMB004001), and Gram-positive Staphylococcus aureus (ATCC 25923), bacteria using the agar-well diffusion method. Results revealed that, out of the three examined plant extracts, the methanol extract of H. sabdariffa L. was the most effective against all tested bacteria. The highest growth inhibition (39.6 ± 0.20 mm) was recorded against E. coli. Additionally, the minimum inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC) of the methanol extract of H. sabdariffa were detected in the case of all tested bacteria. Moreover, an antibiotic susceptibility test revealed that all tested bacteria showed multidrug resistance (MDR). While 50% of tested bacteria were sensitive and 50% were intermediately sensitive to piperacillin/tazobactam (TZP) based on the inhibition zone but still less than the extract. Synergistic assay demonstrated the promising role of using a combination of H. sabdariffa L. and (TZP) against tested bacteria. A surface investigation using a scanning electron microscope of the E. coli treated with TZP, extract, or a combination of the two revealed extremely considerable bacterial cell death. In addition, H. sabdariffa L. has a promising anticancer role versus Caco-2 cells with IC50 of 17.51 ± 0.07 µg/mL and minimal cytotoxicity upon testing versus Vero cells with CC50 of 165.24 ± 0.89 µg/mL. Flow cytometric analysis confirmed that H. sabdariffa extract significantly increased the apoptotic rate of Caco-2-treated cells compared to the untreated group. Furthermore, GC-MS analysis confirmed the existence of various bioactive components in the methanol hibiscus extract. Utilizing molecular docking with the MOE-Dock tool, binding interactions between n-Hexadecanoic acid, hexadecanoic acid-methyl ester, and oleic acid, 3-hydroxypropyl ester were evaluated against the target crystal structures of E. coli (MenB) (PDB ID:3T88) and the structure of cyclophilin of a colon cancer cell line (PDB ID: 2HQ6). The observed results provide insight into how molecular modeling methods might inhibit the tested substances, which may have applications in the treatment of E. coli and colon cancer. Thus, H. sabdariffa methanol extract is a promising candidate to be further investigated for developing alternative natural therapies for infection treatment.

Anticandidal activity of nanocomposite based on nanochitosan, nanostarch and mycosynthesized copper oxide nanoparticles against multidrug-resistant Candida.

Recently, antimicrobial resistance has increased globally particularly Candida infections. Most of antifungal drugs used for treating candidiasis became resistant to most of Candida species. In the current study, a nanocomposite based on mycosynthesized copper oxide nanoparticles (CuONPs), nanostarch, nanochitosan was prepared. Results illustrated that twenty-four Candida isolates were isolated from clinical samples. Furthermore, three Candida strains were selected as the most resistant among others toward commercial antifungal drugs; these selected strains were identified genetically as C. glabrata MTMA 19, C. glabrata MTMA 21 and C. tropicalis MTMA 24. Characterization of the prepared nanocomposite was carried out using physiochemical analysis included Ultraviolet-visible spectroscopy (Uv-Vis), Fourier-Transform Infrared Spectroscopy (FTIR), Scanning Electron Microscopy (SEM), Energy-Dispersive X-ray spectroscopy (EDX) and Transmission Electron Microscopy (TEM). Moreover, the nanocomposite exhibited promising anticandidal activity against C. glabrata MTMA 19, C. glabrata MTMA 21 and C. tropicalis MTMA 24, where the inhibition zones were 15.3, 27 and 28 mm, respectively. Ultrastructure changes observed in nanocomposite-treated C. tropicalis demonstrated disruption of the cell wall which led to cell death. In conclusion, our results confirmed that the novel biosynthesized nanocomposite based on mycosynthesized CuONPs, nanostarch and nanochitosan is a promising anticandidal agent to fight multidrug-resistant Candida.

Potential Antimicrobial and Antibiofilm Properties of Copper Oxide Nanoparticles: Time-Kill Kinetic Essay and Ultrastructure of Pathogenic Bacterial Cells.

Mycosynthesis of nanoparticle (NP) production is a potential ecofriendly technology for large scale production. In the present study, copper oxide nanoparticles (CuONPs) have been synthesized from the live cell filtrate of the fungus Penicillium chrysogenum. The created CuONPs were characterized via several techniques, namely Fourier transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD), transmission electron microscope (TEM), scanning electron microscope (SEM), and energy-dispersive X-ray spectroscopy (EDX). Furthermore, the biosynthesized CuONPs were performed against biofilm forming Klebsiella oxytoca ATCC 51,983, Escherichia coli ATCC 35,218, Staphylococcus aureus ATCC 25,923, and Bacillus cereus ATCC 11,778. The anti-bacterial activity result was shown with the zone of inhibition determined to be 14 ± 0.31 mm, 16 ± 0.53 mm, 11 ± 0.57 mm, and 10 ± 0.57 mm respectively. Klebsiella oxytoca and Escherichia coli were more susceptible to CuONPs with minimal inhibitory concentration (MIC) values 6.25 and 3.12 µg/mL, respectively, while for Staphylococcus aureus and Bacillus cereus, MIC value was 12.5 and 25 µg/mL, respectively. The minimum biofilm inhibition concentration (MBIC) result was more evident, that the CuONPs have excellent anti-biofilm activity at sub-MIC levels reducing biofilm formation by 49% and 59% against Klebsiella oxytoca and Escherichia coli, while the results indicated that the MBIC of CuONPs on Bacillus cereus and Staphylococcus aureus was higher than 200 µg/mL and 256 µg/mL, respectively, suggesting that these CuONPs could not inhibit mature formatted biofilm of Bacillus cereus and Staphylococcus aureus in vitro. Overall, all the results were clearly confirmed that the CuONPs have excellent anti-biofilm ability against Klebsiella oxytoca and Escherichia coli. The prepared CuONPs offer a smart approach for biomedical therapy of resistant microorganisms because of its promoted antimicrobial action, but only for specified purposes.

Antifungal Activity of Biosynthesized Silver Nanoparticles (AgNPs) against Aspergilli Causing Aspergillosis: Ultrastructure Study.

Currently, nanoparticles and nanomaterials are widely used for biomedical applications. In the present study, silver nanoparticles (AgNPs) were successfully biosynthesized using a cell-free extract (CFE) of Bacillus thuringiensis MAE 6 through a green and ecofriendly method. The size of the biosynthesized AgNPs was 32.7 nm, and their crystalline nature was confirmed by XRD, according to characterization results. A surface plasmon resonance spectrum of AgNPs was obtained at 420 nm. Nanoparticles were further characterized using DLS and FTIR analyses, which provided information on their size, stability, and functional groups. AgNPs revealed less cytotoxicity against normal Vero cell line [IC50 = 155 µg/mL]. Moreover, the biosynthesized AgNPs exhibited promising antifungal activity against four most common Aspergillus, including Aspergillus niger, A. terreus, A. flavus, and A. fumigatus at concentrations of 500 µg/mL where inhibition zones were 16, 20, 26, and 19 mm, respectively. In addition, MICs of AgNPs against A. niger, A. terreus, A. flavus, and A. fumigatus were 125, 62.5, 15.62, and 62.5 µg/mL, respectively. Furthermore, the ultrastructural study confirmed the antifungal effect of AgNPs, where the cell wall's integrity and homogeneity were lost; the cell membrane had separated from the cell wall and had intruded into the cytoplasm. In conclusion, the biosynthesized AgNPs using a CFE of B. thuringiensis can be used as a promising antifungal agent against Aspergillus species causing Aspergillosis.

Study of the dual biological impacts of aqueous extracts of normal and gamma-irradiated Galleria mellonella larvae.

Objectives: Galleria mellonella assimilates beeswax using many gut enzymes; however, high doses of gamma radiation have been used to eradicate such pests, affecting its life cycle. In vitro studies of irradiated extracts of G. mellonella against bacterial species as well as three tumour cell lines are demonstrated in the present study. The antibacterial and antitumour effects are compared with those of the non-irradiated Galleria mellonella larval extract. Methods: The effect of different dose levels of gamma irradiation, ranging from 2 to 8 Gy, was tested on G. mellonella lipase, protease, and acid phosphate activities. The antimicrobial activity of un-irradiated and irradiated G. mellonella larval extracts was tested against different gram-positive and gram-negative bacteria and some fungi. The antitumour action was tested against different tumour cell lines. A cytotoxicity assay was performed on normal and irradiated larval extracts against normal human lung fibroblast cells. A microscopic examination of Streptococcus mutants and HepG-2 was performed using transmission and scanning electron microscopy. Results: Optimum results were obtained at 6 Gy, which enhanced maximum enzymatic activity. Maximum antimicrobial activity was obtained against Streptococcus mutants with MIC 31.25 µg/ml at a dose of 6 Gy. A microscopic examination depicted an apoptotic process for irradiated G. mellonella larvae with either Streptococcus mutants or HepG-2. Conclusion: The present study shows a synergistic relationship between the G. mellonella larval extract and a 6 Gy radiation dose for further biomedical applications.

Determination of Therapeutic and Safety Effects of Zygophyllum coccineum Extract in Induced Inflammation in Rats.

Background: Z. coccineum is a facultative plant with many medicinal applications. This study examined the anti-inflammatory activity of Zygophyllum coccineum (Z. coccineum) in an arthritis animal model. Materials and Methods: Seventy-Six Wistar Albino rats of either sex randomly divided into six groups (12/each). The inflammation model was done using Complete Freund's Adjuvant in albino rats. The anti-inflammatory activities of the extract were estimated at different dose levels (15.6, 31, and 60 mg/kg) as well as upon using methotrexate (MTX) as a standard drug (0.3 mg/kg). Paw volume and arthritis index scores have been tested in all examined animals' treatments. Histological examination of joints was also performed. Flow cytometric studies were done to isolated osteoclasts. Cytokines assay as well as biochemical testing was done in the examined samples. Results. In vitro studies reported an IC50 of 15.6 µg/ml for Z. coccineum extract in lipoxygenase inhibition assay (L.O.X.). Moreover, it could be noticed that isorhamnetin-3-O-glucoside, tribuloside, and 7-acetoxy-4-methyl coumarin were the most common compounds in Z. coccineum extract separated using L.C.-ESI-TOF-M.S. (liquid chromatography-electrospray ionization ion-trap time-of-flight mass spectrometry). Microscopic examinations of synovial tissue and hind limb muscles revealed the effect of different doses of Z. coccineum extract on restoring chondrocytes and muscles structures. Osteoclast size and apoptotic rate examinations revealed the protective effect of Z. coccineum extract on osteoclast. The results upon induction of animals and upon treatment using of MTX significantly increased apoptotic rate of osteoclast compared to control, while using of 15.6 µg/ml. for Z. coccineum extract lead to recover regular apoptotic rate demonstrating the protective effect of the extract. Z. coccineum extract regulated the secretion of proinflammatory and anti-inflammatory cytokines. Biochemical tests indicated the safety of Z. coccineum extract on kidney and liver functions. Conclusion. Z. coccineum extract has efficient and safe anti-inflammatory potential in an induced rat model.

From HIV to COVID-19, Molecular mechanisms of pathogens' trade-off and persistence in the community, potential targets for new drug development.

Background: On the staggering emergence of the Omicron variant, numerous questions arose about the evolution of virulence and transmissibility in microbes. Main body of the abstract: The trade-off hypothesis has long speculated the exchange of virulence for the sake of superior transmissibility in a wide array of pathogens. While this certainly applies to the case of the Omicron variant, along with influenza virus, various reports have been allocated for an array of pathogens such as human immunodeficiency virus (HIV), malaria, hepatitis B virus (HBV) and tuberculosis (TB). The latter abide to another form of trade-off, the invasion-persistence trade-off. In this study, we aim to explore the molecular mechanisms and mutations of different obligate intracellular pathogens that attenuated their more morbid characters, virulence in acute infections and invasion in chronic infections. Short conclusion: Recognizing the mutations that attenuate the most morbid characters of pathogens such as virulence or persistence can help in tailoring new therapies for such pathogens. Targeting macrophage tropism of HIV by carbohydrate-binding agents, or targeting the TMPRSS2 receptors to prevent pulmonary infiltrates of COVID-19 is an example of how important is to recognize such genetic mechanisms.

Anticancer, Anticoagulant, Antioxidant and Antimicrobial Activities of Thevetia peruviana Latex with Molecular Docking of Antimicrobial and Anticancer Activities.

Natural origin molecules represent reliable and excellent sources to overcome some medicinal problems. The study of anticancer, anticoagulant, and antimicrobial activities of Thevetia peruviana latex were the aim of the current research. An investigation using high-performance liquid chromatography (HPLC) revealed that the major content of the flavonoids are rutin (11.45 µg/mL), quersestin (7.15 µg/mL), naringin (5.25 µg/mL), and hisperdin (6.07 µg/mL), while phenolic had chlorogenic (12.39 µg/mL), syringenic (7.45 µg/mL), and ferulic (5.07 µg/mL) acids in latex of T. peruviana. Via 1,1-diphenyl-2- picrylhydrazyl (DPPH) radical scavenging, the experiment demonstrated that latex had a potent antioxidant activity with the IC50 43.9 µg/mL for scavenging DPPH. Hemolysis inhibition was 58.5% at 1000 µg/mL of latex compared with 91.0% at 200 µg/mL of indomethacin as positive control. Negligible anticoagulant properties of latex were reported where the recorded time was 11.9 s of prothrombin time (PT) and 29.2 s of the activated partial thromboplastin time (APTT) at 25 µg/mL, compared with the same concentration of heparin (PT 94.6 s and APPT 117.7 s). The anticancer potential of latex was recorded against PC-3 (97.11% toxicity) and MCF-7 (96.23% toxicity) at 1000 µg/mL with IC50 48.26 µg/mL and 40.31 µg/mL, respectively. Disc diffusion assessment for antimicrobial activity recorded that the most sensitive tested microorganisms to latex were Bacillus subtilis followed by Escherichia coli, with an inhibition zone (IZ) of 31 mm with minimum inhibitory concentration (MIC) (10.2 µg/mL) and 30 mm (MIC, 12.51 µg/mL), respectively. Moreover, Candida albicans was sensitive (IZ, 28 mm) to latex, unlike black fungus (Mucor circinelloides). TEM examination exhibited ultrastructure changes in cell walls and cell membranes of Staphylococcus aureus and Pseudomonas aeruginosa treated with latex. Energy scores of the molecular docking of chlorogenic acid with E. coli DNA (7C7N), and Rutin with human prostate-specific antigen (3QUM) and breast cancer-associated protein (1JNX), result in excellent harmony with the experimental results. The outcome of research recommended that the latex is rich in constituents and considered a promising source that contributes to fighting cancer and pathogenic microorganisms.

Promising Endophytic Alternaria alternata from Leaves of Ziziphus spina-christi: Phytochemical Analyses, Antimicrobial and Antioxidant Activities.

Fungal endophytes are considered one of the most important reservoirs of bioactive compounds which defeat resistant microbes. In our study, endophytic Alternaria alternata was isolated from Ziziphus spina-christi and identified morphologically and genetically with accession number OM 331,682. Preliminary phytochemical screening of ethyl acetate (EA) crude extract of A. alternata revealed that this extract contains alkaloids, tannins, flavonoids, glycosides, phenols, and terpenoids. Moreover, the extract was analyzed using gas chromatography-mass spectrometry (GC-MS) which verified the presence of numerous bioactive compounds. Antimicrobial results illustrated that EA crude extract exhibited promising antimicrobial activity against Gram-negative bacteria (Escherichia coli ATCC 11229, Proteus vulgaris RCMB 004, Pseudomonas aeruginosa ATCC 27853, and Klebsiella pneumonia RCMB 003), Gram-positive bacteria (Bacillus subtilis RCMB 015, Staphylococcus aureus ATCC 25923, and Staphylococcus epidermidis ATCC 14990), and unicellular fungi (Candida albicans ATCC 90028). Ultrastructure study of treated K. pneumonia showed remarkably elucidated destruction of the cell wall and cell membrane and leakage of cytoplasmic materials. Furthermore, the extract has potential antioxidant activity where IC50 was 409 µg/mL. Moreover, this extract did not show any toxicity on Vero normal cell line. These findings confirmed that the endophytic A. alternata from Z. spina-christi is a promising source of bioactive compounds which can be used in different biological applications.

Antifungal Activity of Endophytic Aspergillus terreus Extract Against Some Fungi Causing Mucormycosis: Ultrastructural Study.

Endophytes fungi are applied as favorable safe antifungal agents as well as natural bioactive compounds reservoir. In the current study, the inhibitory effect of endophytic fungus was explained by direct antifungal activity against fungi causing mucormycosis, ultrastructural, and determination of active compounds in fungal extract. Endophytic Aspergillus terreus was isolated from healthy Moringa oleifera leaves and identified morphologically and genetically, and was recorded in gene bank with accession number MW444551.1. Phytochemical analysis and gas chromatography-mass spectroscopy (GC-MS) of ethyl acetate crude extract (EACE) of A. terreus were performed. GC-MS results of EACE of A. terreus revealed that fungal extract contains 16 major bioactive compounds with extensive pharmaceutical activities. Furthermore, EACE of A. terreus revealed a promising antifungal activity against fungi causing mucormycosis as Rhizopus oryzae, Mucor racemosus, and Syncephalastrum racemosum, where inhibition zones of EACE (10 mg/ml) were 20, 37, and 18 mm, respectively. Minimum inhibitory concentration (MIC) of EACE was 0.3125 toward M. racemosus, while 1.25 and 2.5 mg/ml against R. oryzae and S. racemosum, respectively. In the same context, treated R. oryzae, M. racemosus, and S. racemosum with EACE of A. terreus revealed elevation of membrane lipid peroxidation which approves membrane leakage. Furthermore, ultrastructure changes were observed which established alteration in both sporangium and hyphal structures; cell membrane and cytoplasm leakage. In conclusion, endophytic A. terreus has an outstanding antifungal activity against fungi causing mucormycosis.

Evaluation of Pleotropic Protective Activity of Capparis spinose Extract on Arthritis Rat Model.

BACKGROUND: Capparis spinosa grows in Asian and Mediterranean desert areas. Different parts of Capparis spinosa, including flowers, have been used in various folk medicine applications. OBJECTIVE: This study aims to evaluate the anti-arthritic potential of ethanolic extract of Egyptian Capparis spinosa flowers in a rat model of rheumatoid arthritis. Moreover, analysis of Capparis spinosa extract was performed using LC-qTOF-MS/MS. METHODS: Animals were split into six groups: negative control group, induced arthritic animals, arthritic rats receiving 7, 14 and 28 mg/kg of Capparis spinosa extract, respectively, in three groups to detect the optimum dose, and the induced group receiving a standard drug. The arthritic score was checked daily for 15 days after induction. After animals were sacrificed, their joints and muscles were subjected to microscopic and ultra-structure examinations. Ex vivo culturing of osteoclasts was performed. Cytokine levels were measured in all examined groups. RESULTS: The results revealed 7 mg/kg of Capparis spinosa extract as the optimal dose, which decreased inflammation signs through controlling chondrocytes, osteoclasts, and levels of inflammatory mediators. CONCLUSION: LC-Mass analysis revealed Capparis spinosa extract to contain a mixture of flavonol glycosides, flavan-3-ols and hydroxycinnamic acid derivatives, which may provide beneficial multifunction in regulating arthritic symptoms.

Enhancement the Mycosynthesis of Selenium Nanoparticles by Using Gamma Radiation.

Selenium is a fundamental trace element of the living system. Microorganisms play a crucial role in the selenium cycle, both in the environment and in life. Biogenic selenium nanoparticles have shown promising prospects for use in medicine as an antioxidant and anticancer agent. In this study, SeNPs were biosynthesized by Penicillium citrinum. The spore suspension which was previously prepared was exposed to different doses of gamma radiation (10, 20, 30, 50, and 60 Gy). SeNPs were then produced by an irradiated P citrinum. UV spectroscopy, transmission electron microscopy, X-ray diffraction, and GSH content were assayed to evaluate the probability of P citrinum synthesizing SeNPs. In conclusion, irradiation of P citrinum by gamma ray enhances the mycosynthesis of SeNPs.

Trichoderma Volatile Organic Compounds as a Biofumigation Tool against Late Blight Pathogen Phytophthora infestans in Postharvest Potato Tubers.

We tested the ability of 14 strains of Trichoderma to emit volatile compounds that decreased or stopped the growth of Phytophthora infestans. Volatile organic compounds (VOCs) emitted from Trichoderma strains designated T41 and T45 inhibited the mycelial growth of P. infestans grown on a laboratory medium by 80 and 81.4%, respectively, and on potato tubers by 93.1 and 94.1%, respectively. Using the DNA sequence analysis of the translation elongation factor region, both Trichoderma strains were identified as Trichoderma atroviride. VOCs emitted by the strains were analyzed, and 39 compounds were identified. The most abundant compounds were 3-methyl-1-butanol, 6-pentyl-2-pyrone, 2-methyl-1-propanol, and acetoin. Electron microscopy of the hyphae treated with T. atroviride VOCs revealed serious morphological and ultrastructural damages, including cell deformation, collapse, and degradation of cytoplasmic organelles. To our knowledge, this is the first report describing the ability of Trichoderma VOCs to suppress the growth of the late blight potato pathogen.

Identification of Novel Bioactive Compound Derived from Rheum officinalis against Campylobacter jejuni NCTC11168.

Gastric diseases are increasing with the infection of Campylobacter jejuni. Late stages of infection lead to peptic ulcer and gastric carcinoma. C. jejuni infects people within different stages of their life, especially childhood, causing severe diarrhea; it infects around two-thirds of the world population. Due to bacterial resistance against standard antibiotic, a new strategy is needed to impede Campylobacter infections. Plants provide highly varied structures with antimicrobial use which are unlikely to be synthesized in laboratories. A special feature of higher plants is their ability to produce a great number of organic chemicals of high structural diversity, the so-called secondary metabolites. Twenty plants were screened to detect their antibacterial activities. Screening results showed that Rheum officinalis was the most efficient against C. jejuni. Fractionation pattern was obtained by column chromatography, while the purity test was done by thin-layer chromatography (TLC). The chemical composition of bioactive compound was characterized using GC-MS, nuclear magnetic resonance, and infrared analysis. Minimal inhibitory concentration (MIC) of the purified compound was 31.25 µg/ml. Cytotoxicity assay on Vero cells was evaluated to be 497 µg/ml. Furthermore, the purified bioactive compound activated human lymphocytes in vitro. The data presented here show that Rheum officinalis could potentially be used in modern applications aimed at the treatment or prevention of foodborne diseases.