Probiotics and the microbiota-gut-brain axis in neurodegeneration: Beneficial effects and mechanistic insights.

Neurodegenerative diseases (NDs) are a group of heterogeneous disorders with a high socioeconomic burden. Although pharmacotherapy is currently the principal therapeutic approach for the management of NDs, mounting evidence supports the notion that the protracted application of available drugs would abate their dopaminergic outcomes in the long run. The therapeutic application of microbiome-based modalities has received escalating attention in biomedical works. In-depth investigations of the bidirectional communication between the microbiome in the gut and the brain offer a multitude of targets for the treatment of NDs or maximizing the patient's quality of life. Probiotic administration is a well-known microbial-oriented approach to modulate the gut microbiota and potentially influence the process of neurodegeneration. Of note, there is a strong need for further investigation to map out the mechanistic prospects for the gut-brain axis and the clinical efficacy of probiotics. In this review, we discuss the importance of microbiome modulation and hemostasis via probiotics, prebiotics, postbiotics and synbiotics in ameliorating pathological neurodegenerative events. Also, we meticulously describe the underlying mechanism of action of probiotics and their metabolites on the gut-brain axis in different NDs. We suppose that the present work will provide a functional direction for the use of probiotic-based modalities in promoting current practical treatments for the management of neurodegenerative-related diseases.

Navigating the future: Microfluidics charting new routes in drug delivery.

Microfluidics has emerged as a transformative force in the field of drug delivery, offering innovative avenues to produce a diverse range of nano drug delivery systems. Thanks to its precise manipulation of small fluid volumes and its exceptional command over the physicochemical characteristics of nanoparticles, this technology is notably able to enhance the pharmacokinetics of drugs. It has initiated a revolutionary phase in the domain of drug delivery, presenting a multitude of compelling advantages when it comes to developing nanocarriers tailored for the delivery of poorly soluble medications. These advantages represent a substantial departure from conventional drug delivery methodologies, marking a paradigm shift in pharmaceutical research and development. Furthermore, microfluidic platformsmay be strategically devised to facilitate targeted drug delivery with the objective of enhancing the localized bioavailability of pharmaceutical substances. In this paper, we have comprehensively investigated a range of significant microfluidic techniques used in the production of nanoscale drug delivery systems. This comprehensive review can serve as a valuable reference and offer insightful guidance for the development and optimization of numerous microfluidics-fabricated nanocarriers.

Computational study of inclusion complexes of V-type nerve agents (VE, VG, VM, VR and VX) with ß-cyclodextrin.

The effective detoxification of organophosphate (OP) nerve agents (OPNAs) is a challenging issue for scientists. The host-guest inclusion complexes of five V-type nerve agents (VE, VG, VM, VR and VX) with ß-cyclodextrin (ß-CD) have been studied by combining quantum mechanical (QM) calculations and molecular dynamics (MD) simulations. The frontier molecular orbital (FMO) and molecular electrostatic potential (MEP) have been analyzed to describe the reactivity parameters and electronic properties. The obtained results clearly reveal that stable complexes were formed in both vacuum and water media, and the complexation process occurred spontaneously. To understand non-covalent interactions, natural bond orbital (NBO) and quantum theory of atoms in molecules (QTAIM) have been used. IR and Raman spectra have been calculated to confirm the formation of complexes and also thermodynamic parameters have been investigated. It was demonstrated that in addition to van der Waals interactions, the presence of intermolecular hydrogen bonds enhances the stability of these complexes. Furthermore, MD simulations were carried out to get a better insight into the inclusion process of the above complexes. From MD simulations, all simulated systems reached full equilibration at 1000 ps and the V-agent molecules consistently remained in the ß-CD cavity and only had vibrational motion inside the cavity. More importantly, MD simulations support the findings of QM calculations and indicate that hydrogen bonding can help the leaving groups of V-agents to be released and them to be hydrolyzed. All results have shown that the VR agent formed the most stable complex with ß-CD molecule than that of other agents.Communicated by Ramaswamy H. Sarma.

Effect of the bare and functionalized single-wall carbon nanotubes on inhibition of asphaltene molecules aggregation: A molecular dynamic simulation.

A comprehensive study has been carried out by utilizing the molecular dynamics technique in order to investigate the behavior of the N-(1-hexylheptyl)-N'-(2-phenylpropanoicacid)-perylene-3,4,9,10-tetracarboxylicbisimide (PAP) molecules in the n-heptane/toluene solution as well as the role of the bare and functionalized single-wall carbon nanotubes (SWCNTs) with the carboxyl groups (-COOH) on the aggregation of PAP molecules. It was found that the CNTs benefit two mechanism of steric hindrance and adsorbing the PAP molecules to suppress the affinity of PAP molecules to association. The results ascertain that the constant amount of the carboxyl groups acts more efficiently in restricting the growth of aggregate size if they are distributed on the surface of a larger CNT. Both of the increased nonbonding interactions between the functionalized CNTs and the PAP molecules, and the number of formed hydrogen bonds between them clearly proved the efficiency of the -COOH groups in improving the stability of PAP molecules. The strength of the adsorption free energies revealed that the PAP molecule shows more tendency to be adsorbed on the surface of CNT modified with carboxyl groups. Increasing the dosage of the -COOH groups on the surface of the CNTs with constant dimension causes an increment in the PAP molecules' solvent accessible surface area (SASA) value, indicating enhanced stability of the PAP molecules. Finally, the results would facilitate future studies on manipulating the asphaltene precipitation in the oil industry.

Synthesis of 4-Hydroxycoumarin-Based Triazoles/Oxadiazoles as Novel Anticancer Agents.

A series of novel 3-substituted-4-hydroxycoumarins 7 and 8 containing (5-aryl-1,3,4-oxadiazol-2-yl)thio or (4-amino-5-aryl-4H-1,2,4-triazol-3-yl)thio moieties have been synthesized and evaluated as anticancer agents. The in vitro MTT assay of compounds against hepatocellular carcinoma (HepG2), breast cancer (MCF7) cells, and a human colorectal adenocarcinoma cell line with epithelial morphology (HT29) indicated that the HepG2 cells had more susceptibility to the tested compounds. Indeed, all compounds (with the exception of 7b, 7c, 7g, and 8g) were more potent than the standard drug doxorubicin against HepG2 cells (IC50 values=1.65-3.83 µM). Although, the better result was obtained with the oxadiazole analog 7h against HepG2 (IC50 =1.65 µM), the N-amino-triazole derivatives 8c, 8e, 8f and, 8h with IC50 values of 1.78-6.34 µM showed potent activity against all tested cell lines. The good drug-like properties and in vitro potency and selectivity of 4-hydroxycoumarins 8 make them as good leads for the development of new anticancer agents.

Correlation of Serum Levels of Interleukine-16, CCL27, Tumor Necrosis Factor-related Apoptosis-inducing Ligand, and B-cell Activating Factor with Multiple Sclerosis Severity.

The pathogenic roles of Interleukine-16 (IL-16), CCL27, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), and B-cell activating factor (BAFF) has been shown in some autoimmune and inflammatory diseases. We aimed to correlate the circulatory changes of such factors with the severity of disease in patients with multiple sclerosis (MS). This case-control study was conducted on 84 MS patients and 83 healthy controls. We measured the serum levels of IL-16, CCL27, TRAIL, and BAFF in all participants by enzyme-linked immune sorbent assay. Using the expanded disability status scale (EDSS), we evaluated the severity of MS. Finally, we assessed the correlation between serum levels of such factors with the severity of MS. We found increased serum levels of CCL27, IL-16, and BAFF in patients with MS compared to those in healthy subjects. However, no difference was found in serum levels of TRAIL between the patients and controls. In addition, a significant positive correlation between serum levels of CCL27, IL-16, TRAIL, and BAFF with disease severity according to EDSS score was determined. We showed higher serum levels of CCL27, BAFF, TRAIL, and IL-16 in MS patients with more severe disabilities than mild forms. Such finding may represent their contribution to the pathogenesis of MS. Blocking such molecules may yield new treatments for MS.

Evaluation the Possible Role of Interleukin-6 and Tumor Necrosis Factor- Alpha in Pathogenesis of Obstructive Sleep Apnea in Obese Patients: A Case-Control Study:.

BACKGROUND: According to a mounting body of evidence, recent observations have highlighted considerable association between obstructive sleep apnea (OSA) syndrome and patients' obesity and inflammation, however the exact underlying mechanisms remain to be fully understood. In this study, the relationship between OSA and Interleukin-6 and Tumor necrosis factor- alpha was assessed in obese patients and their serum concentrations were compared to non-OSA obese subjects. MATERIALS AND METHODS: This case-control study was conducted on forty-six obese OSA patients (body mass indices, BMI30) and 42 obese but otherwise healthy individuals who were admitted to the pulmonary or obesity clinics of the Hazrat-e Rasool General Hospital (Tehran, Iran) between November 2019 and May 2020 were included. The participants completed the NOSAS, EPWORTH and STOPBANG questionnaires. Tumor Necrosis Factor-Alpha (TNF-α) and Interleukin-6 (IL-6) serum concentrations were determined using the enzyme-linked immunosorbent assay (ELISA) method. RESULTS: Compared to the non-OSA group, OSA patients had higher systolic and diastolic blood pressure, pCO2, bicarbonate (HCO3) and hemoglobin and lower high-density lipoprotein (HDL) values. IL-6 and TNF-α serum levels were not significantly different between both groups. Univariate and multivariate linear regression models showed that BMI, systolic blood pressure, pCO2 and HCO3 can positively affect the serum TNF-α and systolic blood pressure and HCO3 can also positively affect the serum IL-6 values in patients with the OSA. CONCLUSION: This investigation suggests that among the OSA patients, the heightened inflammatory profile may be influenced by the high BMI. Furthermore, the exclusive relationship between different disease biomarkers and inflammatory agents in OSA patients is intriguing and needs further research.