Because of their medicinal characteristics, effectiveness, and importance, plant-derived flavonoids have been a possible subject of research for many years, particularly in the last decade. Plants contain a huge number of flavonoids, and Diosmin, a flavone glycoside, is one of them. Numerous in-vitro and in-vivo studies have validated Diosmin’s extensive range of biological capabilities which present antioxidative, antihyperglycemic, anti-inflammatory, antimutagenic, and antiulcer properties. We have presented this review work because of the greater biological properties and influences of Diosmin. We have provided a brief overview of Diosmin, its pharmacology, major biological properties, such as anti-cancer, anti-diabetic, antibacterial, anticardiovascular, liver protection, and neuroprotection, therapeutic approach, potential Diosmin targets, and pathways that are known to be associated with it.

The monoclonal antibodies 6E10 and 4G8 are among the first anti-amyloid monoclonal antibodies against Aβ and the most widely used antibodies in Alzheimer’s disease research. Although the epitopes for 6E10 and 4G8 have been reported to correspond to residues 1–16 and 17–24, a more recent high-resolution mapping approach indicates that 6E10 maps to residues 4–10 while 4G8 maps to residues 18–23. To characterize the binding specificity of both antibodies in greater detail, we used immunoselection of random sequences from phage display library followed by deep sequencing and analysis of resulting patterns from thousands of immunoselected sequences. We found that the minimum sequence required for 6E10 binding is R-x-D with over half (53%) of the immunoselected sequences conforming to this pattern. The vast majority of these sequences contain an H at position x (R-H-D), corresponding to residues 5–7 of the Aβ target sequences, but Y is also permitted at this position in a minority of sequences. For 4G8 we found that the most frequent pattern is F-x-A contained in approximately 30% of the sequences, followed by F-A, L-x(3)-A, L-x-F, and F-F each accounting for approximately 18% of the sequences. The F-x-A motif also occurs in islet amyloid poly peptide which may explain why 4G8 also recognizes amyloid fibrils of this peptide. Immunoselection of random sequences and deep sequencing may also be a facile and efficient means of determining residues critical for antibody binding and validating the specificity of monoclonal antibodies and polyclonal antisera.

The molecular etiology of thyroid carcinoma (TC) and other thyroid diseases which may present malignant precursor lesions is not fully explored yet. The purpose of this study was to estimate frequency, type and clinicopathological value of BRAF exon 15 mutations in different types of cancerous and non-cancerous thyroid lesions originating in an ethnically diverse population.

Several diseases, including atherosclerosis, are characterized by inflammation, which is initiated by leukocyte migration to the inflamed lesion. Hence, genes implicated in the early stages of inflammation are potential therapeutic targets to effectively reduce atherogenesis. Algal-derived polysaccharides are one of the most promising sources for pharmaceutical application, although their mechanism of action is still poorly understood. The present study uses a computational method to anticipate the effect of fucoidan and alginate on interactions with adhesion molecules and chemokine, followed by an assessment of the cytotoxicity of the best-predicted bioactive compound for human monocytic THP-1 macrophages by lactate dehydrogenase and crystal violet assay. Moreover, an in vitro pharmacodynamics evaluation was performed. Molecular docking results indicate that fucoidan has a greater affinity for L-and E-selectin, monocyte chemoattractant protein 1 (MCP-1), and intercellular adhesion molecule-1 (ICAM-1) as compared to alginate. Interestingly, there was no fucoidan cytotoxicity on THP-1 macrophages, even at 200 µg/mL for 24 h. The strong interaction between fucoidan and L-selectin in silico explained its ability to inhibit the THP-1 monocytes migration in vitro. MCP-1 and ICAM-1 expression levels in THP-1 macrophages treated with 50 µg/mL fucoidan for 24 h, followed by induction by IFN-γ, were shown to be significantly suppressed as eight- and four-fold changes, respectively, relative to cells treated only with IFN-γ. These results indicate that the electrostatic interaction of fucoidan improves its binding affinity to inflammatory markers in silico and reduces their expression in THP-1 cells in vitro, thus making fucoidan a good candidate to prevent inflammation.

Liver X receptors (LXRs) are ligand-dependent transcription factors that are activated by metabolites of cholesterol, oxysterols, and a number of synthetic agonists. LXRs play potent anti-atherogenic roles in part by stimulating the efflux of cholesterol from macrophage foam cells. The LXR-induced expression of ATP-binding cassette transporter (ABC)-A1 and Apolipoprotein E (ApoE) in macrophages is essential for the stimulation of cholesterol efflux and the prevention of atherosclerotic development. Unfortunately, the signaling pathways underlying such regulation are poorly understood and were therefore investigated in human macrophages. The expression of ApoE and ABCA1 induced by synthetic or natural LXR ligands [TO901317, GW3965, and 22-(R)-hydroxycholesterol (22-(R)-HC), respectively] was attenuated by inhibitors of c-Jun N-terminal kinase (JNK) (curcumin and SP600125) and phosphoinositide 3-kinase (PI3K) (LY294002). Similar results were obtained with ABCG1 and LXR-α, two other LXR target genes. LXR agonists activated several components of the JNK pathway (SEK1, JNK and c-Jun) along with AKT, a downstream target for PI3K. In addition, dominant negative mutants of JNK and PI3K pathways inhibited the LXR-agonists-induced activity of the ABCA1 and LXR-α gene promoters in transfected cells. LXR agonists also induced the binding of activator protein-1 (AP-1), a key transcription factor family regulated by JNK, to recognition sequences present in the regulatory regions of the ApoE and ABCA1 genes. These studies reveal a novel role for JNK and PI3K/AKT signaling in the LXR-regulated expression in macrophages of several key genes implicated in atherosclerosis.

Relationship between soil cobalt and vitamin B12 levels in the liver of livestock in Saudi Arabia: role of competing elements in soils