Zygophyllum coccineum, an edible halophytic plant, is part of the traditional medicine chest in the Mediterranean region for symptomatic relief of diabetes, hypertension, wound healing, burns, infections, and rheumatoid arthritis pain. The current study aimed to characterize Z. coccineum phytoconstituents, and the evaluations of the anti-microbial-biofilm, and anti-cancers bioactivities of the plant’s mother liquor, i.e., aqueous-ethanolic extract, and its subsequent fractions. The in silico receptors interaction feasibility of Z. coccineum major constituents with Staph GyraseB, and human topoisomerase-IIβ (h-TOP-IIβ) were conducted to confirm the plant’s anti-microbial and anti-cancer biological activities. Thirty-eight secondary metabolites of flavonoids, stilbene, phenolic acids, alkaloids, and coumarin classes identified by LC-ESI-TOF-MS spectrometric analysis, and tiliroside (kaempferol-3-O-(6′′′′-p-coumaroyl)-glucoside, 19.8%), zygophyloside-F (12.78%), zygophyloside-G (9.67%), and isorhamnetin-3-O-glucoside (4.75%) were identified as the major constituents. A superior biofilm obliteration activity established the minimum biofilm eradication concentration (MBEC) for the chloroform fraction at 3.9–15.63 µg/mL, as compared to the positive controls (15.63–31.25 µg/mL) against all the microbial strains that produced the biofilm under study, except the Aspergillus fumigatus. The aqueous-ethanolic extract showed cytotoxic effects with IC₅₀ values at 3.47, 3.19, and 2.27 µg/mL against MCF-7, HCT-116, and HepG2 cell-lines, respectively, together with the inhibition of h-TOP-IIβ with IC₅₀ value at 45.05 ng/mL in comparison to its standard referral inhibitor (staurosporine, IC₅₀, 135.33 ng/mL). This conclusively established the anti-cancer activity of the aqueous-ethanolic extract that also validated by in silico receptor-binding predicted energy levels and receptor-site docking feasibility of the major constituents of the plant’s extract. The study helped to authenticate some of the traditional phytomedicinal properties of the anti-infectious nature of the plant.

P-Nitrophenol (PNP) is considered to be one of nitrophenol derivatives of diesel exhaust particles. PNP is a major metabolite of some organophosphorus compounds. PNP is a persistent organic pollutant as well as one of endocrine-disrupting compounds. Consequently, bioaccumulation of PNP potentiates toxicity. The objectives of the current study were to assess in vivo adverse effects of long-term low doses of PNP exposure on reproductive system during development stage. Twnety-eight-day-old male Japanese quails were orally administered different doses of PNP (0, 0.01, 0.1, 1 mg/kg body weight) daily for 2.5 months. Testicular histopathology, hormones, caspase-3 (CASP3), and claudin-1 (CLDN1) tight junction protein, as well as plasma hormones were analyzed. The results revealed that long-term PNP exposure caused testicular histopathological changes such as vacuolation of spermatogenic cell and spermatocyte with significant testicular and cloacal gland atrophy. PNP activated CASP3 enzyme that is an apoptosis-related cysteine peptidase. Besides, it disrupted the expression of CLDN1. Furthermore, a substantial decrease in plasma concentrations of luteinizing hormone (LH) and testosterone was observed after 2 and 2.5 months in the PNP-treated groups. Meanwhile, the pituitary LH did not significantly change. Site of action of PNP may be peripheral on testicular development and/or centrally on the hypothalamic–pituitary–gonadal axis through reduction of pulsatile secretion of gonadotrophin-releasing hormone. Consequently, it may reduce the sensitivity of the anterior pituitary gland to secrete LH. In conclusion, PNP induced profound endocrine disruption in the form of hormonal imbalance, induction of CASP3, and disruption of CLDN1 expression in the testis. Hence, it may hinder the reproductive processes.

With the rising incidence of hepatocellular carcinoma (HCC) from non-alcoholic steatohepatitis (NASH), identifying new metabolic readouts that function in metabolic pathway perpetuation is still a demand. The study aimed to compare the metabolic signature between NASH and NASH-HCC patients to explore novel reprogrammed metabolic pathways that might modulate cancer progression in NASH patients. NASH and NASH-HCC patients were recruited and screened for metabolomics, and isotope-labeled lipidomics were targeted and profiled using the EXION-LCTM system equipped with a Triple-TOFTM 5600+ system. Results demonstrated significantly (p ≤ 0.05) higher levels of triacylglycerol, AFP, AST, and cancer antigen 19-9 in NASH-HCC than in NASH patients, while prothrombin time, platelet count, and total leukocyte count were decreased significantly (p ≤ 0.05). Serum metabolic profiling showed a panel of twenty metabolites with 10% FDR and p ≤ 0.05 in both targeted and non-targeted analysis that could segregate NASH-HCC from NASH patients. Pathway analysis revealed that the metabolites are implicated in the down-regulation of necroptosis, amino acid metabolism, and regulation of lipid metabolism by PPAR-α, biogenic amine synthesis, fatty acid metabolism, and the mTOR signaling pathway. Cholesterol metabolism, DNA repair, methylation pathway, bile acid, and salts metabolism were significantly upregulated in NASH-HCC compared to the NASH group. Metabolite–protein interactions network analysis clarified a set of well-known protein encoding genes that play crucial roles in cancer, including PEMT, IL4I1, BAAT, TAT, CDKAL1, NNMT, PNP, NOS1, and AHCYL. Taken together, reliable metabolite fingerprints are presented and illustrated in a detailed map for the most predominant reprogrammed metabolic pathways that target HCC development from NASH.

Patients with diabetes mellitus often suffer from chronic wounds due to wound healing impairment. Considering the increased prevalence of diabetes, this would predispose significant medical, economic, and social problems. These chronic wounds are frequently infected with pathogenic bacteria like Pseudomonas aeruginosa, which complicates the situation and makes the wound healing process more difficult. Therefore, there is a high need for therapeutic alternatives to the currently available treatments. Plants are vital sources of many bioactive compounds with multiple biological activities. We elucidated the wound healing possibility and antibacterial effect of Cycas thouarsii n-butanol fraction (CTBF) for the first time. Also, CTBF's phytochemical fingerprint was investigated using the LC-MS/MS technology. Interestingly, CTBF revealed antibacterial activity against P. aeruginosa isolates with minimum inhibitory concentrations range 16-128 µg/mL. Regarding the wound healing potential, we used in vivo experiment on diabetic rats. Remarkably CTBF caused a significant reduction (p 0.05) in the levels of forkhead box O1, matrix metalloproteinases 9, and chemokine (C-C motif) ligand 20. Additionally, it led to a substantial increase (p 0.05) in the level of transforming growth factor β1. Moreover, CTBF improved the wound histological features by increasing the collagen area percentage. Regarding the immunohistochemical studies, CTBF resulted in a strong positive epidermal growth factor and a moderate positive caspase 9 immunoreaction in the epidermis and sebaceous glands of the wounds. Therefore, CTBF could be a promising source of bioactive compounds with wound healing and antibacterial activities. Finally, molecular docking was attempted using MOE software to investigate the binding mode of the major identified compounds in the matrix metalloproteinase 9 (MMP-9) receptor (PDB code: 1GKC).