Current Stem Cell Research & Therapy - Volume 15, Issue 7, 2020

Macrophages M2 polarization have been taken as an anti-inflammatory progression during inflammation. Natural plant-derived products, with potential therapeutic and preventive activities against inflammatory diseases, have received increasing attention in recent years because of their whole regulative effects and specific pharmacological activities. However, the molecular mechanisms about how different kinds of natural compounds regulate macrophages polarization still unclear. Therefore, in the current review, we summarized the detailed research progress on the active compounds derived from herbal plants with regulating effects on macrophages, especially M2 polarization. These natural occurring compounds including flavonoids, terpenoids, glycosides, lignans, coumarins, alkaloids, polyphenols and quinones. In addition, we extensively discussed the cellular mechanisms underlying the M2 polarization for each compound, which could provide potential therapeutic strategies aiming macrophages M2 polarization.

Differentiation from RAW264.7 cells to osteoclasts rely on many signaling pathways, such as NF-ΚB, MAPK, Akt and others. However, the specific underlying mechanisms are not clear. Recently, much works have focused on the inhibitory effects of plant derived compounds in the differentiation from RAW264.7 to osteoclasts. However, the specific mechanisms remain unclear. In this paper, we summarize a lot of plant derived compounds which exert blocking effect on the progression of differentiation via signaling pathways.

Excessive bone resorption has been recognized play a major role in the development of bone-related diseases such as osteoporosis, rheumatoid arthritis, Paget's disease of bone, and cancer. Phospholipase Cγ (PLCγ) family members PLCγ1 and PLCγ2 are critical regulators of signaling pathways downstream of growth factor receptors, integrins, and immune complexes and play a crucial role in osteoclast. Ca2+ signaling has been recognized as an essential pathway to the differentiation of osteoclasts. With growing attention and research about natural occurring compounds, the therapeutic use of natural active plant-derived products has been widely recognized in recent years. In this review, we summarized the recent research on PLCγ signaling in bone marrow stem cells and the use of several natural compounds that were proven to inhibit RANKL-mediated osteoclastogenesis via modulating PLCγ signaling pathways.

Renal cell carcinoma (RCC) is one of the common urologic neoplasms, and its incidence has been increasing over the past several decades; however, its pathogenesis is still unknown up to now. Recent studies have found that in addition to tumor cells, other cells in the tumor microenvironment also affect the biological behavior of the tumor. Among them, macrophages exist in a large amount in tumor microenvironment, and they are generally considered to play a key role in promoting tumorigenesis. Therefore, we summarized the recent researches on macrophage in the invasiveness and progression of RCC in latest years, and we also introduced and discussed many studies about macrophage in RCC to promote angiogenesis by changing tumor microenvironment and inhibit immune response in order to activate tumor progression. Moreover, macrophage interactes with various cytokines to promote tumor proliferation, invasion and metastasis, and it also promotes tumor stem cell formation and induces drug resistance in the progression of RCC. The highlight of this review is to make a summary of the roles of macrophage in the invasion and progression of RCC; at the same time to raise some potential and possible targets for future RCC therapy.

Osteoarthritis(OA) is a common degenerative orthopedic disease with multiple pathologic changes in joints affecting large populations worldwide. No treatment can reverse the progress of OA. Since exosomes were first reported in 1983, researches have been conducted to explore the mechanisms and therapeutic potential of exosomes in treating OA. Exosomes derived from Mesenchymal stem cells have attracted increasing attention in tackling the disease. This article summarizes the current advances and challenges in exosomes for OA, which may providea reference for further research.

Mesenchymal Stem Cells (MSCs) exhibit enormous therapeutic potential because of their indispensable regenerative, reparative, angiogenic, anti-apoptotic, and immunosuppressive properties. MSCs can best differentiate into mesodermal cell lineages, including osteoblasts, adipocytes, muscle cells, endothelial cells and chondrocytes. Specific differentiation of MSCs could be induced through limited conditions. In addition to the relevant differentiation factors, drastic changes also occur in the microenvironment to conduct it in an optimal manner for particular differentiation. Recent evidence suggests that the mitochondria participate in the regulating of direction and process of MSCs differentiation. Therefore, our current review focuses on how mitochondria participate in both osteogenesis and adipogenesis of MSC differentiation. Besides that, in our current review, we try to provide a further understanding of the relationship between the behavior of mitochondria and the direction of MSC differentiation, which could optimize current cellular culturing protocols for further facilitating tissue engineering by adjusting specific conditions of stem cells.

Gastric cancer (GC) is the fourth-most common cancer in the world, with an estimated 1.034 million new cases in 2015, and the third-highest cause of cancer deaths, estimated at 785,558, in 2014. Early diagnosis and treatment greatly affect the survival rate in patients with GC: the 5-year survival rate of early GC reaches 90%-95%, while the mortality rate significantly increases if GC develops to the late stage. Recently, studies for the role of RhoA in the diseases have become a hot topic, especially in the development of tumors. A study found that RhoA can regulate actin polymerization, cell adhesion, motor-myosin, cell transformation, and the ability to participate in the activities of cell movement, proliferation, migration, which are closely related to the invasion and metastasis of tumor cells. However, the specific role of RhoA in tumor cells remains to be studied. Therefore, our current study aimed to briefly review the role of RhoA in GC, especially for its associated signaling pathways involved in the GC progression.

Simvastatin, lovastatin, rosuvastatin, pravastatin and cerivastatin belong to the statin family, which are competitive inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A. As the rate-limiting enzyme in the pathway of cholesterol metabolism, statins are classically prescribed to patients as lipidlowering agents. However, statins also possess several extra bioactivities, including anti-inflammatory, antiviral and anti-tumor. Interestingly, the most essential mechanism of these activities is that statins could regulate the expression of cell adhesion molecules (CAMs), especially, targeting lymphocytes function-associated molecules (LFA)-1, macrophage (Mac)-1 and intercellular adhesion molecules (ICAM)-1. Therefore, in this paper, we discussed the regulatory effect of statins on CAMs among different diseases. In addition, we provided speculation for the role of statins in treating orthopedic disease.

Background: Cardiovascular disease (CVD), including disorders of cardiac muscle and vascular, is the major cause of death globally. Many unsuccessful attempts have been made to intervene in the disease's pathogenesis and treatment. Stem cell-based therapies, as a regeneration strategy, cast a new hope for CVD treatment. One of the most well-known stem cells is mesenchymal stem cells (MSCs), classified as one of the adult stem cells and can be obtained from different tissues. These cells have superior properties, such as proliferation and highly specialized differentiation. On the other hand, they have the potential to modulate the immune system and anti-inflammatory activity. One of their most important features is the secreting the extracellular vesicles (EVs) like exosomes (EXOs) as an intercellular communication system mediating the different physiological and pathophysiological affairs. Methods: In this review study, the importance of MSC and its secretory exosomes for the treatment of heart disease has been together and specifically addressed and the use of these promising natural and accessible agents is predicted to replace the current treatment modalities even faster than we imagine. Results: MSC derived EXOs by providing a pro-regenerative condition allowing innate stem cells to repair damaged tissues successfully. As a result, MSCs are considered as the appropriate cellular source in regenerative medicine. In the plethora of experiments, MSCs and MSC-EXOs have been used for the treatment and regeneration of heart diseases and myocardial lesions. Conclusion: Administration of MSCs has been provided a replacement therapeutic option for heart regeneration, obtaining great attention among the basic researcher and the medical doctors.

The Human Genome Project (HGP) announced in 2001 that it had sequenced the entire human genome, yielding nearly complete human DNA. About 98.5 percent of the human genome has been found to be non-coding sequences. Long non-coding RNA (lncRNA) is a non-coding RNA with a length between 200 and 100,000 nucleotide units. Because of shallow research on lncRNA, it was believed that it had no biological functions, but exists as a by-product of the transcription process. With the development of high-throughput sequencing technology, studies have shown that lncRNA plays important roles in many processes by participating in epigenetics, transcription, translation and protein modification. Current researches have shown that lncRNA also has an important part in the pathogenesis of osteoporosis. Osteoporosis is a common disorder of bone metabolism, also a major medical and socioeconomic challenge worldwide. It is characterized by a systemic reduction in bone mass and microstructure changes, which increases the risk of brittle fractures. It is more common in postmenopausal women and elderly men. However, the roles of lncRNA and relevant mechanisms in osteoporosis remain unclear. Based on this background, we hereby review the roles of lncRNA in osteoporosis, and how it influences the functions of osteoblasts and osteoclasts, providing reference to clinical diagnosis, treatment and prognosis of osteoporosis.

Current Stem Cell Research & Therapy, 2019, 14(8): 683-697 Heyong Yin’s affiliation should be: Department of Orthopaedics, Beijing Friendship Hospital, Capital Medical University, Beijing China; Zexing Yan’s affiliation should be: Department of Orthopaedics, Shandong Provincial Hospital Affiliated to Shandong University, No.324, Road Jing Wu Wei Qi, Jinan 250021, Shandong, China. The Original Paragraph Provided is Mentioned Below: Fanxiao Liu1, Qingqi Meng2, Heyong Yin3,* and Zexing Yan3,* 1Department of Orthopaedics, Shandong Provincial Hospital Affiliated to Shandong University, No.324, Road Jing Wu Wei Qi, Jinan 250021, Shandong, China; 3Department of Trauma Surgery, University of Regensburg, Am biopark 9, 93049 Regensburg, Germany