Chimeric antigen receptors (CARs) have a unique facet of synthetic biology and offer a paradigm shift in personalized medicine as they can use and redirect the patient's immune cells to attack cancer cells. CAR‐natural killer (NK) cells combine the targeted specificity of antigens with the subsequent intracellular signaling ability of the receptors to increase their anti‐cancer functions. Importantly, CAR‐NK cells can be utilized as universal cell‐based therapy without requiring human leukocyte antigen (HLA) matching or earlier contact with tumor‐associated antigens (TAAs). Indeed, CAR‐NK cells can be adapted to recognize various antigens, hold higher proliferation capacity, and in vivo persistence, show improved infiltration into the tumors, and the ability to overcome the resistant tumor microenvironment leading to sustained cytotoxicity against tumors. Accumulating evidence from recent in vivo studies rendering CAR‐NK cell anti‐cancer competencies renewed the attention in the context of cancer immunotherapy, as these redirected effector cells can be used in the development of the “off‐the‐shelf” anti‐cancer immunotherapeutic products. In the current review, we focus on the therapeutic efficacy of CAR‐NK cell therapies for treating various human malignancies, including hematological malignancies and solid tumors, and will discuss the recent findings in this regard, with a special focus on animal studies.

Due to the overexpression or amplification of human epidermal growth factor receptor 2 (HER2) with poor prognosis in a myriad of human tumors, recent studies have focused on HER2-targeted therapies. Deregulation in HER2 signaling pathways is accompanied by sustained tumor cells growth concomitant with their migration and also tumor angiogenesis and metastasis by stimulation of proliferation of a network of blood vessels. A large number of studies have provided clear evidence that the emerging HER2-directed treatments could be the outcome of patients suffering from HER2 positive breast and also gastric/gastroesophageal cancers. Thanks to its great anti-tumor competence, immunotherapy using HER2-specific chimeric antigen receptor (CAR) expressing immune cell has recently attracted increasing attention. Human T cells and also natural killer (NK) cells can largely be found in the tumor microenvironment, mainly contributing to the tumor immune surveillance. Such properties make them perfect candidate for genetically modification to express constructed CARs. Herein, we will describe the potential targets of the HER2 signaling in tumor cells to clarify HER2-mediated tumorigenesis and also discuss recent findings respecting the HER2-specific CAR-expressing immune cells (CAR T and CAR NK cell) for the treatment of HER2-expressing tumors.

The aim of this study was to find the role of TLR2 signaling pathway in reducing osteoclast activity and promoting osteoblast growth by inducing a combination of Aloe vera and cancellous bovine xenograft (XCB) into dental extraction socket. Forty-eight Cavia cobayas were used. They were divided into eight groups (n=6). For control group, their mandibular incisors were extracted and filled with PEG. For treatment groups, they were extracted and filled with XCB, Aloe vera and the combination of Aloe vera and XCB. The first four groups were sacrificed after 7 days and the other groups after 30 days. Immunohistochemistry and histopathology examination were conducted to examine TLR2, TNFα, OPG, collagen-1, and the osteoblast and osteoclast expressions. The expressions of TLR2, OPG and Collagen-1, as well as the number of osteoblast were increased. Meanwhile, the expressions of TNFα and osteoclast were decreased. The study finding was that TLR2 signaling pathway influenced alveolar bone osteogenesis process by reducing osteoclast activity and stimulating osteoblast growth induced by the combination of Aloe vera and XCB.

Objective Ellagic acid (EA), a phenolic antioxidant, has benefits in bone health and wound healing. The combination of EA and hydroxyapatite (HA) (EA-HA) is expected to increase osteogenesis. The aim of this study was to analyze osteogenesis after application of EA-HA according to the number of osteoblasts and osteoclasts in the bone and the expression of the receptor activator of nuclear factor kappa- ligand (RANKL), osteoprotegerin (OPG), and osteocalcin (OCN) protein. Materials and Methods Thirty Wistar rats were assessed with bone defects created in the left femur. The defects were filled with EA-HA and then sutured. Control groups were filled with polyethylene glycol (PEG) or HA. Each group was sacrificed either 7 or 14 days after treatment. Results The defects filled with EA-HA exhibited the highest number of osteoblasts and the greatest expression of OPG and OCN at both day 7 and day 14 (p = 0.000). Conversely, treatment with EA-HA resulted in lower numbers of osteoclasts and reduced RANKL staining at both time points (p = 0.000). Conclusions EA-HA can increase osteogenesis in bone defects by increasing the number of osteoblasts and the expression of OPG and OCN.

INTRODUCTION: SARS-CoV-2 develops well in the oral mucosa because, it is the first contact area with the virus. The oral mucosa is highly expressed with angiotensin-converting enzyme 2 (ace2) and makes the virus replicated in the epithelial cells and produce both oral lesions and oral symptoms. this review aimed to describe the oral mucosal symptoms and lesions related to SarS-coV-2-infected patients that have been reported around the world. eViDeNce acQUiSitiON: a literature search was performed on PubMed, ScienceDirect and Google Scholar, from February to October 5, 2020, focusing on cOViD-19 (SarS-coV-2) oral lesions and oral symptoms. EVIDENCE SYNTHESIS: Eighteen studies were identified with a total of 25 cases describing the oral symptoms and oral mucosal lesions of the SarS-coV-2 infection. the oral symptoms related to the SarS-coV-2 infection included dysgeusia, ageusia, a burning mouth sensation, a dry mouth and severe halitosis. the oral mucosal lesions varied from ulceration and depapilation to pseudomembranous, maculae, nodules and plaque. the mucosal lesions related to the skin lesions were in the form of crusty lips, multiple ulcerations and rashes, targeted lesions, blisters and vesiculobullous lesions. CONCLUSIONS: The manifestations of the SARS-CoV-2 infection in the oral cavity are non-specific. The oral mucosal lesions that occur mimic the Herpes zoster virus infection, the Herpes simplex virus infection, Varicella and hand, foot and mouth disease, and the oral mucosal lesions with the skin manifestations (e.g. erythema multiforme).