CAR-NK cell therapy in AML: Current treatment, challenges, and advantage.

Over the last decade, discovery of novel therapeutic method has been attention by the researchers and has changed the therapeutic perspective of hematological malignancies. Although NK cell play a pivotal role in the elimination of abnormal and cancerous cells, there are evidence that NK cell are disarm in hematological malignancy. Chimeric antigen receptor NK (CAR-NK) cell therapy, which includes the engineering of NK cells to detect tumor-specific antigens and, as a result, clear of cancerous cells, has created various clinical advantage for several human malignancies treatment. In the current review, we summarized NK cell dysfunction and CAR-NK cell based immunotherapy to treat AML patient.

The dysfunction of natural killer cells is essential for the development of type 1 diabetes.

Type 1 diabetes (T1D) is characterized by destruction of pancreatic insulin-producing beta cells by immune cells. In general, environmental and genetic factors can lead to immunological self-tolerance in TID. It is clear that the innate immune system, especially natural killer (NK) cells, is involved in the pathogenesis of T1D. Aberrant NK cell frequencies associated with dysregulation of inhibitory and activating receptors contribute to the initiation and progression of T1D. As T1D is incurable and the metabolic disturbances caused by T1D severely impact patients, a better understanding of NK cell behavior in T1D may facilitate disease treatment strategies. The current review focuses on the role of NK cell receptors in T1D and also highlights ongoing efforts to manipulate key checkpoints in NK cell-targeted therapies.

NK cell dysfunction is linked with disease severity in SARS-CoV-2 patients.

SARS-CoV-2 first raised from Wuhan City, Hubei Province in November 2019. The respiratory disorder, cough, weakness, fever are the main clinical symptoms of coronavirus disease 2019 (COVID-19) patients. Natural Killer (NK) cells as a first defense barrier of innate immune system have an essential role in early defense against pulmonary virus. They kill the infected cells by inducing apoptosis or the degranulation of perforin and granzymes. Collectively, NK cells function are coordinated by the transmitted signals from activating and inhibitory receptors. It is clear that the cytotoxic function of NK cells is disrupted in COVID-19 patients due to the dysregulation of activating and inhibitory receptors. Therefore, better understanding of the activating and inhibitory receptors mechanism could facilitate the treatment strategy in clinic. To improve the efficacy of immunotherapy in COVID-19 patients, the functional detail of NK cell and manipulation of their key checkpoints are gathered in current review.

Minocycline can reduce testicular apoptosis related to varicocele in male rats.

The current research aimed to assess the impacts of Minocycline on varicocele-induced regulation of apoptotic-related genes and oxidative stress in the testis of adult Wistar rats. Thirty-two rats were divided into 4 groups: sham, varicocele (VcI), varicocele treated with Minocycline (VcI + Mno) for 56 days and healthy rats treated with minocycline (Mno). After 8 weeks, the oxidative stress markers levels in serum were investigated, afterwards, the level of Bax and Bcl-2 expression were assessed through 'immunocytochemistry' and RT-qPCR assays. Also, the rate of apoptosis was evaluated through the TUNEL method. Johnson's score, 'the width of epithelium' and 'seminiferous tubules diameter' were ameliorated in the VcI + Mno group in comparison with the Vcl group. Administration of Minocycline raised the 'Glutathione peroxidase' and 'Superoxide dismutase' levels in serum and declined the Malondialdehyde level in serum (p = 0.001). Furthermore, current study represented that minocycline reduced Bax and enhanced the expression of Bcl-2 gene and protein in comparison with the Vcl group (p < 0.05). In addition, Minocycline administration significantly declined the rate of apoptosis in germ cells (p < 0.05). Our study demonstrated that the administration of Minocycline could improve testicular injury in varicocele-induced rats by its antioxidant activity.

Adipose-derived stem cells: An appropriate selection for osteogenic differentiation.

Mesenchymal stem cells (MSCs) are a major component of various forms of tissue engineering. MSCs have self-renewal and multidifferential potential. Osteogenic differentiation of MSCs is an area of attention in bone regeneration. One form of MSCs are adipose-derived stem cells (ASCs), which can be simply harvested and differentiated into several cell lineages, such as chondrocytes, adipocytes, or osteoblasts. Due to special properties, ASCs are frequently used in vitro and in vivo bone regeneration. Identifying factors involved in osteogenic differentiation of ASCs is important for better understanding the mechanism of osteogenic differentiation. Different methods are used to stimulate osteogenesis of ASCs in literature, including common osteogenic media, growth factors, hormones, hypoxia, mechanical and chemical stimuli, genetic modification, and nanotechnology. This review article provides an overview describing the isolation procedure, characterization, properties, current methods for osteogenic differentiation of ASCs, and their basic biological mechanism.

Upregulation of FSHR and PCNA by administration of coenzyme Q10 on cyclophosphamide-induced premature ovarian failure in a mouse model.

Cyclophosphamide (CTX) has been broadly used in the clinic for the treatment of autoimmune disorders and ovarian cancer. The process of chemotherapy has significant toxicity in the reproductive system as it has detrimental effects on folliculogenesis, which leads to an irreversible premature ovarian failure (POF). Coenzyme Q10 (CoQ10) has positive impacts on the reproductive system due to its antioxidant properties, protecting the cells from free-radical oxidative damage and apoptosis. However, little is known about the possible synergistic effect of CTX and CoQ10 on the expression of genes involved in folliculogenesis, such as proliferation cell nuclear antigen (PCNA) and follicle-stimulating hormone receptor (FSHR). A total of 32 NMRI mice were applied and divided into four groups, including healthy control, CTX, CTX + CoQ10, and CoQ10 groups. The effects of CoQ10 on CTX-induced ovarian injury and folliculogenesis were examined by histopathological and real-time quantitative reverse transcription-polymerase chain reaction analyses. The rates of fertilization (in vitro fertilization), embryo development, as well as the level of reactive oxygen species (ROS) in metaphase II (MII) mouse oocytes after PMSG/HCC treatment were also assessed. Results showed that the treatment with CTX decreased the mRNA expression of PCNA and FSHR, IVF rate, and embryo development whereas the application of CoQ10 successfully reversed those factors. CoQ10 administration significantly enhanced histological morphology and decreased ROS levels and the number of atretic follicles in the ovary of CTX-treated mice. In conclusion, it seems that the protective effect of CoQ10 is exerted via the antioxidant and proliferative properties of this substance on CTX-induced ovarian damage.

Panax ginseng Extract Improves Follicular Development after Mouse Preantral Follicle 3D Culture.

OBJECTIVE: Panax ginseng is a popular traditional herb that has been used in complementary and alternative medicine in eastern Asia, and it possesses pharmacologically active compounds like ginsenosides (GSs). This study aimed to investigate the impact of Panax ginseng extract (PGE) at different concentrations on in vitro follicular function and development in a three-dimensional (3D) culture system fabricated using sodium alginate after 12 days of culture. MATERIALS AND METHODS: In this experimental study, preantral follicles (n=661) were mechanically isolated from the ovaries of 14-day-old female NMRI mice using 29-gauge insulin syringes. Follicles were individually capsulated within sodium alginate, and divided into four groups including control and experimental groups 1, 2, and 3. Then, they were cultured for 12 days in the medium supplemented with different concentrations of PGE (0, 50, 100, and 500 µg/ mL, for control groups and groups 1, 2 and 3, respectively). At the end of the culture period, the mean diameter and maturation of follicles, follicular steroid production, mRNA expression level of proliferating cell nuclear antigen (PCNA) and follicle stimulating hormone receptor (FSH-R), and reactive oxygen species (ROS) levels in collected metaphase-II (MII) oocytes were determined. RESULTS: The mean diameter of follicles in group 2 was significantly increased as compared to other groups (P<0.001). The percentages of the survival and maturation rate and levels of secreted hormones were higher in group 2 than the other groups (P<0.05). Follicles cultured in the presence of PGE 100 µg/mL had higher levels of proliferation cell nuclear antigen (PCNA) and follicle stimulating hormone receptor (FSH-R) mRNA expression in comparison to other groups (P<0.05). Moreover, oocytes collected from groups 2 and 3 had lower levels of ROS as compared to other groups (P<0.05). CONCLUSION: Our results suggest that PGE at the concentration of 100 µg/mL induces higher follicular function and development in the 3D culture system.