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Currently, ziconotide is the only clinical used N-type VGCCs blocker peptide for chronic intractable pain. However, ziconotide causes different adverse effects. The intrathecal route of administration also impairs its use in a more significant number of patients. In this sense, peptides isolated from animal venoms or their synthetic forms that modulate or block VGCCs channels seem to be a relevant prototype for developing new analgesics efficacious and well tolerated by patients.Polysialic acid (polySia) is a unique carbohydrate polymer produced on the neuronal cell adhesion molecule (NCAM) in many cancer cells. It strongly correlates with the migration and invasion of tumor cells and aggressive, metastatic disease, and poor clinical prognosis in the clinic. Its synthesis is catalyzed by two polysialyltransferases (polySTs), ST8SiaIV (PST) and ST8SiaII (STX). Therefore, selective inhibition of polySTs presents a therapeutic opportunity to inhibit tumor invasion and metastasis due to NCAM polysialylation. It has been proposed that NCAM polysialylation could be inhibited by two types of heparin inhibitors, low molecular heparin (LMWH) and heparin tetrasaccharide (DP4). This review summarizes the interactions between Polysialyltransferase Domain (PSTD) in ST8SiaIV and CMP-Sia, and between the PSTD and polySia; and how LMWH and DP4 inhibit these interactions. Our NMR studies indicate that LMWH is a more effective inhibitor than DP4 for inhibition of NCAM polysialylation. The NMR identification of heparin-binding sites in the PSTD may provide insight into the design of specific inhibitors of polysialylation.

Calcium dysregulation has been proposed to play a causative role in the development of Alzheimer’s disease pathology. Pregabalin is a compound already approved for human use, marketed as the prescription drug Lyrica. It binds the α2-δ subunit of P/Q-type voltage gated calcium channels, lowering calcium influx and providing effective treatment for epilepsy and neuropathic pain.

We hypothesize that increased resting calcium in neuronal processes near amyloid plaques plays a role in the development of neuritic dystrophies and further progression of amyloid pathology.

5XFAD mice were treated orally for 12 weeks with pregabalin, then immunoblotting and immunofluorescent imaging were used to quantify neuritic dystrophy and amyloid deposition in pregabalin compared to placebo-treated mice.

The treatment did not decrease markers of neuritic dystrophy or amyloid deposition. The image analysis of neuritic dystrophy on a plaque-by-plaque basis showed a small non-significant increase in the relative proportion of LAMP1 to Aβ42 in plaques with areas of 50 -450 μm2 in the cortex of pregabalin-treated mice. In addition, there was a statistically significant positive correlation between the measured cerebral concentration of pregabalin and the relative levels of BACE1 and Aβ in the cortex. This relationship was not observed in the hippocampus, and there was no increase in average Aβ levels in pregabalin treated mice compared to placebo. We confirmed previous findings that smaller amyloid plaques are associated with a greater degree of neuritic dystrophy.

Pregabalin may have an effect on Aβ that merits further investigation, but our study does not suggest that pregabalin contributes substantially to amyloid pathology.

Pregabalin may have an effect on Aβ that merits further investigation, but our study does not suggest that pregabalin contributes substantially to amyloid pathology.Lichens are commonly used as essential traditional medicines to treat various conditions, including skin disorders, wounds, digestive, respiratory, obstetric, and gynecological problems in many cultures in Africa, Asia, Europe, Haitian, Oceania, and North and South America. Lichens have been deeply investigated for their phytochemical properties, and to date, numerous compounds (also known as substances) have been successfully isolated from the extracts. However, the low solubility and bioavailability of pure lichen substances have been widely recognized as the significant issues hindering their biological applications. Recently, several groups have investigated the properties and the potential applications of lichen metabolites-based liposomal formulations and revealed a substantial improvement in their solubility, bioactivity, and toxicity in the animal. Thus, in this topical review, we aimed to provide an overview of liposomal structures, the efficacy of liposomal formulations, as well as their beneficial effects as compared to the free compounds themselves.

Ovarian cancer is one of the leading causes of death worldwide. selleckchem Polymers have low cytotoxicity and high functional ability and hence used for drug delivery systems, tissue engineering, and polymer therapeutics. In drug delivery systems, polymer-drug conjugates have shown considerable promise, especially in anticancer chemotherapy.

Anticancer drug delivery systems (DDS) deliver drugs to the tumor site, leading to reduced exposure to healthy cells and reduced side effects. Efforts have been made to develop effective DDS using stimuli-responsive polymers like thermo sensitive and pH-sensitive polymers.

Elastin-like polypeptides (ELP), one of the thermoresponsive polymers, have been identified as drug carriers in anticancer therapy. ELP-drug conjugates have the potential and can be used effectively in combination with hyperthermia for targeting drugs to solid tumors. This review reports on the use of ELPs in cancer therapy, its biomedical applications, and recent developments to target medicines to solid ovarian tumors.

Elastin-like polypeptides (ELP), one of the thermoresponsive polymers, have been identified as drug carriers in anticancer therapy. ELP-drug conjugates have the potential and can be used effectively in combination with hyperthermia for targeting drugs to solid tumors. This review reports on the use of ELPs in cancer therapy, its biomedical applications, and recent developments to target medicines to solid ovarian tumors.

Our study seeks to obtain data to assess the impacts of circPUM1 on pancreatic cancer (PC) and its mechanism.

The expression of circPUM1 and miR-200c-3p in PC and normal tissues and PC cell lines was collected and detected. Subsequently, dual-luciferase assay-based verification of the binding site of the two was carried out. After interfering with circPUM1 expression in MIAPaCa-2 and PANC-1 cells, cell proliferation, viability, apoptosis rate, invasion ability, glucose consumption, and lactate production were measured by MTT, colony formation, flow cytometry, Transwell assays, and glucose and lactate assay kits. Additionally, western blot was utilized for assessing PI3K/AKT signaling pathway-related proteins. From the results, highly expressed circPUM1 and miR-200c-3p in PC tissues and cells were proved.

Down-regulation of circPUM1 expression significantly inhibited cell proliferation, cell viability, invasion, and glycolysis, while increasing the apoptosis rate. Down-regulated circPUM1 led to the inhibition of the PI3K/AKT signaling pathway activity in PC cells, while up-regulated circPUM1 increased its activity.