CAR-NK Cell: A New Paradigm in Tumor Immunotherapy.

The tumor microenvironment (TME) is greatly multifaceted and immune escape is an imperative attribute of tumors fostering tumor progression and metastasis. Based on reports, the restricted achievement attained by T cell immunotherapy reflects the prominence of emerging other innovative immunotherapeutics, in particular, natural killer (NK) cells-based treatments. Human NK cells act as the foremost innate immune effector cells against tumors and are vastly heterogeneous in the TME. Currently, there exists a rapidly evolving interest in the progress of chimeric antigen receptor (CAR)-engineered NK cells for tumor immunotherapy. CAR-NK cells superiorities over CAR-T cells in terms of better safety (e.g., absence or minimal cytokine release syndrome (CRS) and graft-versus-host disease (GVHD), engaging various mechanisms for stimulating cytotoxic function, and high feasibility for 'off-the-shelf' manufacturing. These effector cells could be modified to target various antigens, improve proliferation and persistence in vivo, upturn infiltration into tumors, and defeat resistant TME, which in turn, result in a desired anti-tumor response. More importantly, CAR-NK cells represent antigen receptors against tumor-associated antigens (TAAs), thereby redirecting the effector NK cells and supporting tumor-related immunosurveillance. In the current review, we focus on recent progress in the therapeutic competence of CAR-NK cells in solid tumors and offer a concise summary of the present hurdles affecting therapeutic outcomes of CAR-NK cell-based tumor immunotherapies.

Stem cell in neurodegenerative disorders; an emerging strategy.

Neurodegenerative disorders are a diversity of disorders, surrounding Alzheimer's (AD), Parkinson's (PD), Huntington's diseases (HD), and amyotrophic lateral sclerosis (ALS) accompanied by some other less common diseases generally characterized by either developed deterioration of central or peripheral nervous system structurally or functionally. Today, with the viewpoint of an increasingly aging society, the number of patients with neurodegenerative diseases and sociomedical burdens will spread intensely. During the last decade, stem cell technology has attracted great attention for treating neurodegenerative diseases worldwide because of its unique attributes. As acknowledged, there are several categories of stem cells being able to proliferate and differentiate into various cellular lineages, highlighting their significance in the context of regenerative medicine. In preclinical models, stem cell therapy using mesenchymal stem/stromal cells (MSCs), hematopoietic stem cells (HSCs), and neural progenitor or stem cells (NPCs or NSCs) along with pluripotent stem cells (PSCs)-derived neuronal cells could elicit desired therapeutic effects, enabling functional deficit rescue partially. Regardless of the noteworthy progress in our scientific awareness and understanding of stem cell biology, there still exist various challenges to defeat. In the present review, we provide a summary of the therapeutic potential of stem cells and discuss the current status and prospect of stem cell strategy in neurodegenerative diseases, in particular, AD, PD, ALS, and HD.

Subjective perceptions and physiological variables during weaning from mechanical ventilation.

BACKGROUND: As costs related to mechanical ventilation increase, clear indicators of patients' readiness to be weaned are needed. Research has not yet yielded a consensus on physiological variables that are consistent correlates of weaning outcomes. Subjective perceptions rarely have been examined for their contribution to successful weaning. OBJECTIVE: To explore the subjective perceptions of dyspnea, fatigue, and self-efficacy and selected physiological variables in patients being weaned from mechanical ventilation. METHODS: Data were collected prospectively on 68 patients being weaned from mechanical ventilation. Subjective perceptions were measured by using 3 visual analog scales; physiological variables were measured by using the Burns Weaning Assessment Program and a patient profile. Weaning outcomes were recorded 24 hours after data collection. RESULTS: Participants were primarily white women and required mechanical ventilation for a mean of less than 4 days. Participants reported mild dyspnea, moderate fatigue, and high weaning self-efficacy. High PaO2, low PaCO2, stable hemodynamic status, adequate cough and swallow reflexes, no metabolic changes, and no abdominal problems were associated with complete weaning (P = .05). Subjective perceptions were associated with physiological variables but not with weaning outcomes. CONCLUSIONS: Multidimensional assessment of both primary and secondary indicators of readiness to be weaned is necessary for timely, efficient weaning from mechanical ventilation. Primary assessments include physiological variables related to gas exchange, hemodynamic status, diaphragmatic expansion, and airway clearance. Secondary assessments include perceptions related to key physiological variables. Additional research is needed to determine the predictive value of physiological variables and perceptions of dyspnea, fatigue, and self-efficacy.