Parkinson’s disease (PD) is the second most common progressive neurodegenerative disorder associated with increased oxidative stress, the underlying vital process contributing to cell death. Tanshinone IIA (TAN) is a phytomedicine with a documented activity in treating many CNS disorders, particularly PD owing to its unique anti-inflammatory and antioxidant effect. However, its clinical utility is limited by its poor aqueous solubility, short half-life, and hence low concentration reaching targeted cells. This work aimed to develop a biocompatible chitosan-coated nanostructured lipid carriers (CS-NLCs) for effective brain delivery of TAN for PD management. The proposed nanosystem was successfully prepared using a simple melt-emulsification ultra-sonication method, optimized and characterized both in vitro and in vivo in a rotenone-induced PD rat model. The developed TAN-loaded CS-NLCs (CS-TAN-NLCs) showed good colloidal properties (size ≤ 200 nm, PDI ≤ 0.2, and ζ-potential + 20 mV) and high drug entrapment efficiency (> 97%) with sustained release profile for 24 h. Following intranasal administration, CS-TAN-NLCs succeeded to achieve a remarkable antiparkinsonian and antidepressant effect in diseased animals compared to both the uncoated TAN-NLCs and free TAN suspension as evidenced by the conducted behavioral tests and improved histopathological findings. Furthermore, biochemical evaluation of oxidative stress along with inflammatory markers, nuclear factor-kabba β (NF-Kβ) and cathepsin B further confirmed the potential of the CS-TAN-NLCs in enhancing brain delivery and hence the therapeutic effect of TAN of treatment of PD. Accordingly, CS-TAN-NLCs could be addressed as a promising nano-platform for the effective management of PD. Graphical abstract

Healthcare textiles are gaining great attention in the textile industry. Electrospun nanofibers are considered the golden soldiers due to their strength, flexibility, and eco-friendly properties. The present study aimed to evaluate the potency of polyvinyl alcohol (PVA) nanofibers loaded with newly biosynthesized silver nanoparticles (Ag-NPs) as a wound healing dressing. Chocolate-band snail (Eobania vermiculata) mucus (which is part of the Mollusca defense system) was used as a novel reducing and stabilizing agent. Data indicated the effectiveness of Eobania vermiculata’s mucus in silver nanoparticle synthesis after a 24 h incubation time. The biosynthesized AgNPs-SM showed a 13.15 nm particle size, −22.5 mV ζ potential, and 0.37 PDI, which proved the stability of the synthesized nanoparticles. Eobania vermiculata mucus and AgNPs-SM showed potent antibacterial activity, especially against Pseudomonas aeruginosa. The electrospinning technique was applied in the fabrication of PVA/AgNPs-SM nanofibers, which were homogenous with a fine diameter of about 100–170 nm and showed a significantly high antimicrobial activity. In vitro and in vivo studies revealed that PVA/AgNPs-SM nanofibers were safe and efficiently enhanced the wound healing process (typical histological picture of the proliferative phase with compact and well aligned collagen fibers in the dermal tissue after 12 days) together with bacterial growth inhibition in the infected skin area.

Toxoplasmosis may become a fatal disease in immunodeficient, diabetic patients, pregnant women, and infants. Hence, the diligent search for new effective treatment is among the major concerns worldwide. The well-dispersed multi-walled carbon nanotubes lined with ZnO (ZnO-MWCNT), graphene oxide (GO-NPs), and zinc oxide (ZnO-NPs) were successfully synthesized through rapid and facile hydrothermal arc discharge technique (HTADT). The antiparasitic effects of ZnO-NPs, GO-NPs, and ZnO-MWCNT were investigated in mice infected with Toxoplasma gondii. The percent of tachyzoites reduction were detected. The observed results demonstrated that ZnO-MWCNT revealed a significant reduction in the parasite count reached 61% in brain tissues, followed by liver (52%), then spleen (45%). The assessments of antiparasitic, inflammatory, and anti-inflammatory cytokines confirmed the superior activity of ZnO-MWCNT as antiparasitic agent, which paves the way for the employment of ZnO-MWCNT as a treatment for the acute RH strain of T. gondii infection in vivo.

Nitrogen-containing atoms in their core structures have been exclusive building blocks in drug discovery and development. One of the most significant and well-known heterocycles is the 1,3,4-thidiazole nucleus, which is found in a wide range of natural products and therapeutic agents. In the present work, certain tris-1,3,4-thiadiazole derivatives (6, 7) were synthesized through a multi-step synthesis approach. All synthesized compounds were characterized using different spectroscopic tools. Previously, thiadiazole compounds as anti-Toxoplasma gondii agents have been conducted and reported in vitro. However, this is the first study to test the anti-Toxoplasma gondii activity of manufactured molecular hybrids thiadiazole in an infected mouse model with the acute RH strain of T. gondii. All the observed results demonstrated compound (7)’s powerful activity, with a considerable reduction in the parasite count reaching 82.6% in brain tissues, followed by liver and spleen tissues (65.35 and 64.81%, respectively). Inflammatory and anti-inflammatory cytokines assessments proved that Compound 7 possesses potent antiparasitic effect. Furthermore, docking tests against TgCDPK1 and ROP18 kinase (two major enzymes involved in parasite invasion and egression) demonstrated compound 7’s higher potency compared to compound 6 and megazol. According to the mentioned results, tris-1,3,4-thiadiazole derivatives under test can be employed as potent antiparasitic agents against the acute RH strain of T. gondii.

Bacterial pneumonia is considered one of the most virulent diseases with high morbidity and mortality rates, especially in hospitalized patients. Moreover, bacterial resistance increased over the last decades which limited the therapy options to carbapenem antibiotics. Hence, the metallo-β-lactamase-producing bacteria were deliberated as the most deadly and ferocious infectious agents. Sulphadiazine-ZnO hybrids biological activity was explored in vitro and in vivo against metallo-β-lactamases (MBLs) producing Klebsiella pneumoniae. Docking studies against NDM-1 and IMP-1 MBLs revealed the superior activity of the 3a compound in inhibiting both MBLs enzymes in a valid reliable docking approach. The MBLs inhibition enzyme assay revealed the remarkable sulphadiazine-ZnO hybrids inhibitory effect against NDM-1 and IMP-1 MBLs. The tested compounds inhibited the enzymes both competitively and noncompetitively. Compound 3b-ZnO showed the highest antibacterial activity against the tested metallo-β-lactamase producers with an inhibition zone (IZ) diameter reaching 43 mm and a minimum inhibitory concentration (MIC) reaching 2 µg/mL. Sulphadiazine-ZnO hybrids were tested for their in vitro cytotoxicity in a normal lung cell line (BEAS-2Bs cell line). Higher cell viability was observed with 3b-ZnO. Biodistribution of the sulphadiazine-ZnO hybrids in the lungs of uninfected rats revealed that both [^124I]3a-ZnO and [^124I]3b-ZnO hybrids remained detectable within the rats’ lungs after 24 h of endotracheal aerosolization. Moreover, the residence duration in the lungs of [^124I]3b-ZnO (t_1/2 4.91 h) was 85.3%. The histopathological investigations confirmed that compound 3b-ZnO has significant activity in controlling bacterial pneumonia infection in rats.

Meningitis caused by Klebsiella pneumoniae and Pseudomonas aeruginosa has lately become a prevalent cause of the central nervous system (CNS) infection. Bacterial invasion into the subarachnoid space prompts the releasing mechanism of chemokines and pro-inflammatory cytokines. The present study aimed to compare K. pneumoniae and P. aeruginosa meningitis concerning the memory, pro-inflammatory mediators and brain histopathological changes at different time intervals in adult Albino rats. The animals were sacrificed at three time intervals comprising 5, 10 and 15 days after meningitis induction. Cerebrospinal fluid (CSF) culture, relative brain weights, complete blood analysis, biochemical markers, levels of cytokine, chemokine and brain-derived neurotrophic factor (BDNF), neurotransmitter acetylcholine esterase (AChE) activity, and the brain histopathology of the infected rats in comparison to those in the control group were assessed. There was a significant increase in the levels of pro-inflammatory cytokines and chemokines including TNF-α, IL-1β, IL-6 and AChE after 5 days of bacterial meningitis infection with both K. pneumoniae and P. aeruginosa. The histopathological analysis of the cerebral cortex in the P. aeruginosa meningitis model at different time intervals revealed abundant numbers of dilated and congested blood vessels with severe hemorrhage, cerebral infarct, intracellular and extracellular vacuoles, and gliosis. Fifteen days post infection, a significant reduction in the brain tissue weight was observed. The meningitis model employing P. aeruginosa exhibited more evident time-dependent severity compared to K. pneumoniae, which may advocate its validity as a simple and effective research model to study meningitis of the CNS. This model may be utilized for further investigation to ascertain the molecular and biological association between bacterial meningitis and the development of the pathophysiological hallmarks underlying Alzheimer’s disease in preclinical and clinical setups. Clinical extrapolation based on studies employing animal disease models should be carefully interpreted.