As a \"silent threat,\" Alzheimer\'s disease (AD) is quickly rising to the top of the list of costly and troublesome diseases facing humanity. It is growing to be one of the most troublesome and expensive conditions, with annual health care costs higher than those of cancer and comparable to those of cardiovascular disorders. One of the main pathogenic characteristics of AD is the deficiency of the neurotransmitter acetylcholine (ACh) which plays a vital role in memory, learning, and attention. Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) play a crucial role in hydrolyzing ACh. Consequently, a frequent therapy approach for AD is the suppression of AChE and BChE to improve cholinergic neurotransmission and reduce cognitive symptoms. The accumulation of amyloid plaques (Aβ) is a primary factor contributing to neurodegenerative diseases, particularly AD. Glycogen synthase kinase-3β (GSK3-β) is regarded as a pivotal player in the pathophysiology of AD since dysregulation of this kinase affects all major hallmarks of the disease, such as tau phosphorylation, Aβ aggregation, memory, neurogenesis, and synaptic function. One of the most challenging and risky issues in modern medicinal chemistry is the urgent and ongoing need for the study and development of effective therapeutic candidates for the treatment of AD. A significant class of heterocyclic molecules that can target the complex and multifactorial pathogenesis of AD are fused thiophene derivatives. The goal of the current review is to demonstrate the advancements made in fused thiophene derivatives\' anti-AD activity. It also covers their mechanisms of action and studies of the structure-activity relationships in addition to the compilation of significant synthetic routes for fused thiophene derivatives with anti-AD potential. This review is intended to stimulate new ideas in the search for more rationale designs of derivatives based on fused thiophene, hoping to be more potent in treating AD.

UNASSIGNED: Arsenic has been reported to induce apoptosis in malignant tumor cells. Therefore, it has been investigated as a chemotherapy. From a mechanistic standpoint, the mitochondrial apoptosis pathway, mediated by GSK-3β, plays an important role in tumor cell apoptosis. Nonetheless, the regulation of GSK-3β by arsenic remains controversial. The study aimed to clarify the mechanism of GSK-3β in arsenic-induced apoptosis of tumor cells.
UNASSIGNED: We included 19 articles, which conducts the role of GSK-3β in the process of arsenic-induced tumor cell apoptosis by the meta-analysis.
UNASSIGNED: Compared with that of control group, the expression of GSK-3β (SMD= -0.92, 95% CI (-1.78, -0.06)), p-Akt (SMD= -5.46,95% CI (-8.67, -2.24)) were increased in the arsenic intervention group. Meanwhile, the combined treatment of arsenic and Akt agonists can inhibit p-GSK-3β. Using the dose and time subgroup analysis, it was shown that the low-dose (<5 μmol/L) and sub-chronic (>24 h) arsenic exposure could inhibit the expression of p-Akt (P < 0.05). In the subgroup analysis of GSK-3β sites, arsenic could inhibit p-Akt and GSK-3β (Ser9) (SMD = -0.95, 95% CI (-1.56, -0.33)). There was a positive dose-response relationship between arsenic and p-GSK-3β when the dose of arsenic was less than 8 μmol/L. The expression of Mcl-1 and pro-caspase-3 were decreased, while the loss of mitochondrial membrane potential and cleaved-caspase-3 increased significantly when arsenic stimulated GSK-3β (Ser9) (P < 0.05).
UNASSIGNED: The study revealed that arsenic could induce tumor cell apoptosis, by inhibiting p-Akt/GSK-3β, and triggering the Mcl-1-dependent mitochondrial apoptosis pathway.

The current rapid spread of the novel coronavirus (SARS-CoV-2) causing coronavirus disease 2019 (COVID-19) calls for a rapid response from the research community. Lithium is widely used to treat bipolar disorder, but has been shown to exhibit antiviral activity. This brief review took a systematic approach to identify six in vitro studies reporting on the influence of lithium on coronaviral infections. We propose mechanistic investigation of the influence of lithium - alone and with chloroquine - on the SARS-CoV-2 infection.

Glycogen Synthase Kinase-3 (GSK-3) is a constitutively dynamic, omnipresent serine/threonine protein kinase regularly called as a \"multitasking kinase\" due to its pliable function in diverse signaling pathways. It exists in two isoforms i.e., GSK-3α and GSK-3β. Inhibition of GSK-3 may be useful in curing various diseases such as Alzheimer\'s disease, type II diabetes, mood disorders, cancers, chronic inflammatory agents, stroke, bipolar disorders and so on, but the approach poses significant challenges. Lithium was the first GSK-3β inhibitor to be used for therapeutic outcome and has been effectively used for many years. In recent years, a large number of structurally diverse potent GSK-3β inhibitors are reported. The present review focuses on the recent developments in the area of medicinal chemistry to explore the diverse chemical structures of potent GSK-3β inhibitors and also describes its structure-activity relationships (SAR) and molecular binding interactions of favorable applicability in various diseases.

Soy isoflavones are dietary components for which an association has been demonstrated with reduced risk of prostate cancer (PCa) in Asian populations. However, the exact mechanism by which these isoflavones may prevent the development or progression of PCa is not completely understood. There are a growing number of animal and in vitro studies that have attempted to elucidate these mechanisms. The predominant and most biologically active isoflavones in soy products, genistein, daidzein, equol, and glycetin, inhibit prostate carcinogenesis in some animal models. Cell-based studies show that soy isoflavones regulate genes that control cell cycle and apoptosis. In this review, we discuss the literature relevant to the molecular events that may account for the benefit of soy isoflavones in PCa prevention or treatment. These reports show that although soy isoflavone-induced growth arrest and apoptosis of PCa cells are plausible mechanisms, other chemo protective mechanisms are also worthy of consideration. These possible mechanisms include antioxidant defense, DNA repair, inhibition of angiogenesis and metastasis, potentiation of radio- and chemotherapeutic agents, and antagonism of estrogen- and androgen-mediated signaling pathways. Moreover, other cells in the cancer milieu, such as the fibroblastic stromal cells, endothelial cells, and immune cells, may be targeted by soy isoflavones, which may contribute to soy-mediated prostate cancer prevention. In this review, these mechanisms are discussed along with considerations about the doses and the preclinical models that have been used.