Current Molecular Medicine - Volume 21, Issue 1, 2021

The COVID-19 plague is hitting mankind. Several viruses, including SARS-CoV-1, MERS-CoV, EBOV, and SARS-CoV-2, use the endocytic machinery to enter the cell. Genomic variants in NPC1, which encodes for the endo-lysosomal Niemann-Pick type C1 protein, restricts the host-range of viruses in bats and susceptibility to infections in humans. Lack of NPC1 and its pharmacological suppression inhibits many viral infections including SARS-CoV-1 and Type I Feline Coronavirus Infection. Antiviral effects of NPC1-inhibiting drugs for COVID-19 treatment should be explored.

Pluripotent stem cells (PSCs) are powerful tools for studying developmental biology and neuronal diseases. Conventional differentiation protocols require several intermediate states and different culture conditions, inefficiently generating mixed subtypes of neuronal cells with immature characteristics. Direct programming of PSCs by forced expression of neuronal transcription factors has shown rapid cell fate determination with high purity as it can bypass sequential developmental steps that traditional culture requires. In this review, we focus on neuronal differentiation from PSCs to specific subtypes by various transcription factors. Furthermore, the potential applications and limitations of this novel technology are discussed.

Melanoma is a serious type of skin cancer, which develops in melanocyte cells. Although it is less common than some other skin cancers, it can be far more dangerous if not treated at an early stage because of its ability to spread rapidly to other organs. Heat shock proteins (HSP) are intracellular molecular chaperones of naive proteins, which are induced in response to stressful conditions. HSP is released into the extracellular milieu and binds to Toll-like receptors (TLRs) to regulate immune responses, such as cytokine and chemokine release. HSPs can release and bind to tumor-specific antigens, with cross-presentation of major histocompatibility complex (MHC) class I antigens. TLRs are innate immune system receptors, involved in the melanoma growth pathway through HSP activation. Melanocytes express TLR4 and TLR9 to modulate immune responses. Many TLR ligands are considered as proper adjuvant candidates, as they can activate dendritic cells. Targeting some TLRs, such as TLR7 and TLR9, is an available option for treating melanoma. In this review, we aimed to determine the relationship between TLRs and HSP groups in melanoma.

Glioma is known as one of very important tumors that is associated with high rate of mortality worldwide. The mean rate of survival of these patients has not changed (approximately 14 months) even with improvements in comprehensive therapeutic approaches, such as chemotherapy, radiation, and surgery. Therefore, it seems that new therapeutic or developed platforms are needed. In this regard, more understanding about genetic and epigenetic modifications in the glioma, could contribute to finding and developing these platforms. Among epigenetic mechanisms, circular RNAs have crucial roles in the glioma pathogenesis. Reported by several studies, some of the abilities of circRNAs include the exhibition of tissue specificity in humans and regulation of genes. Research has also confirmed the participation of circRNAs in different pathological or biological procedures, including migration, invasion, and apoptosis of glioma. Herein, we summarized circular RNAs involved in glioma.

Background: Alzheimer's disease (AD) is the most common progressive neurodegenerative disorder characterized by senile plaques and neurofibrillary tangles (NFTs). The amyloid-oligomer hypothesis indicates that the buildup of toxic oligomers in vivo is likely to impair memory and synaptic function. Methods: In our study, a kind of novel recombinant chimeric 12x(Aβ1-15-Th) antigen was developed as 12-mer Aβ1-42-like assembly vaccine. We designed this 12x(Aβ1-15- Th) antigen to mimic the assembly states of Aβ1-42 using twelvefold Aβ1–15 (B cell epitopes of human Aβ1-42) and foreign human T helper (Th) epitopes (as the T cell epitopes of Aβ1-42) constructs. Its immunogenicity as a subunit vaccine was tested on C57/BL6 mice, and the efficacy was shown by applying it to AD mice. Results: This 12x(Aβ1-15-Th) vaccine induced robust Aβ-specific antibodies in 3xTg- AD and C57/BL6 mice. As early immunotherapeutic agent of AD, the 12x(Aβ1-15-Th) vaccine significantly improved the behavior performance of aged 3 x Tg-AD mice, and reduced the levels of soluble Aβ oligomers and soluble Aβ in the brain. In aged 3 x Tg- AD mice, immunotherapy with the 12x(Aβ1-15-Th) vaccine could prevent Aβ-induced decrease of synaptic proteins, which suggested that it had neuroprotective effects on the brain. Conclusion: The novel recombinant 12x(Aβ1-15-Th) chimeric vaccine targeting of pathological conformations of Aβ oligomers has shown obvious neuroprotective benefits in the preclinical AD model mouse, which indicates that it is a good candidate vaccine for the prophylaxis of AD.

High incidence of articular cartilage defects is still a major challenge in orthopedic and trauma surgery worldwide. It also has great socioeconomic effects as it is the major cause of disability in industrialized countries. This highlights the essential need for new treatments. Knowledge about the factors that have been implicated in the pathogenesis of cartilage diseases, including changes in the composition and structure of cartilaginous extracellular matrix (ECM), molecular factors and environmental signaling pathways could help the development of innovative therapeutic strategies. It is consensuses that the success of any technology aiming to repair chondral defects will be dependent upon its ability to produce tissues that most closely replicate the mechanical and biochemical properties of native cartilage. Increasing the knowledge about cartilage tissue and its molecular biomarkers could help find new and useful therapeutic approaches in cartilage damage. This review tries to describe cartilage tissue biology in detail and discuss different available therapeutic modalities with their pros and cons. New cartilage regeneration strategies and therapies, focusing on cellbased therapy and tissue engineering, and their underlying molecular and cellular bases will be pointed out as well.

Objective: We aim to investigate the anticancer effects and mechanisms of icaritin against breast cancer. Materials and Methods: Both estrogen receptor (ER) positive breast cancer cells MCF- 7 and ER-negative MDA-MB-231 cells were employed. We examined the effects of icaritin on the proliferation and migration by wound healing assay and transwell assay. Cell apoptosis and cell cycle of MCF-7 and MDA-MB-231 cells were analyzed using Flow cytometry. Cell autophagy of MCF-7 and MDA-MB-231 cells was assessed by western blotting, acridine orange staining and confocal microscopy. We also detected the expression of apoptosis-related genes by western blotting. In addition, an autophagy inhibitor was used to investigate whether cytoprotective autophagy was induced. Meanwhile, an ER inhibitor was utilized to explore whether ER was involved in autophagy. Results: Icaritin inhibited the proliferation and migration, and induced cell cycle arrest of both MDA-MB-231 and MCF-7 cells. Icaritin significantly induced apoptosis of MDA-MB- 231 cells by activating caspase-3. And icaritin stimulated autophagy in MCF-7 cells, as evidenced by increased LC3II/LC3I, enhanced p62 degradation, the accumulation of endogenous LC3 puncta formation, and the increased autophagy flux. Icaritin induced autophagy through upregulating the phosphorylation of AMPK and ULK1. Chloroquine, an autophagy inhibitor, increased icaritin-induced apoptosis and proliferation inhibition of MCF-7 cells. Meanwhile, tamoxifen, an ER inhibitor, reversed icaritin-induced autophagy and proliferation inhibition of MCF-7 cells. Conclusion: Our study demonstrated that the antitumor effects of icaritin against breast cancer are related to ER, which suggested that the status of ER should be considered in the clinical application of icaritin.