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Clustered regularly interspaced short palindromic repeats (CRISPR) is described as RNA mediated adaptive immune system defense, which is naturally found in bacteria and archaea. CRISPR-Cas9 has shown great promise for cancer treatment in cancer immunotherapy, manipulation of cancer genome and epigenome and elimination or inactivation of carcinogenic viral infections. However, many challenges remain to be addressed to increase its efficacy, including off-target effects, editing efficiency, fitness of edited cells, immune response and delivery methods. Here, we explain CRISPR-Cas classification and its general function mechanism for gene editing. Then, we summarize these preclinical CRISPR-Cas9-based therapeutic strategies against cancer. Moreover, the challenges and improvements of CRISPR-Cas9 clinical applications will be discussed.

BackgroundJianpi-yangwei (JPYW), a traditional Chinese medicine (TCM), helps to nourish the stomach and spleen and is primarily used to treat functional declines related to aging. This study aimed to explore the antiaging effects and mechanism of JPYW by employing aCaenorhabditis elegansmodel.MethodsWild-typeC. elegansN2 worms were cultured in growth medium with or without JPYW, and lifespan analysis, oxidative and heat stress resistance assays, and other aging-related assays were performed. The effects of JPYW on the levels of superoxide dismutase (SOD) and the expression of specific genes were examined to explore the underlying mechanism of JPYW.ResultsCompared to control worms, JPYW-treated wild-type worms showed increased survival times under both normal and stress conditions (P P clk-2and upregulated expression levels of the antiaging genesdaf-16,skn-1, andsir-2.1were observed in the JPYW group compared to the control group.ConclusionOur findings suggest that JPYW extends the lifespan ofC. elegansand exerts antiaging effects by increasing the activity of an antioxidant enzyme (SOD) and by regulating the expression of aging-related genes. This study not only indicates that this Chinese compound exerts antiaging effects by activating and repressing target genes but also provides a proven methodology for studying the biological mechanisms of TCMs.

Liangyi Gao (LYG), a traditional Chinese medicine, is composed of Ginseng and Radix Rehmanniae Preparata, both of which have been shown to have antiaging properties. In Eastern countries, LYG is used to delay functional declines related to aging and has an obvious antiaging effect in clinical practice. However, little data from evidence-based medicine is available regarding whether LYG is beneficial overall, particularly with respect to lifespan, and how LYG functions. To address these issues, Caenorhabditis elegans, a useful organism for such studies, was employed to explore the antiaging effect and mechanism of LYG in this study. The results showed that LYG could obviously extend lifespan and slow aging-related declines in N2 wild-type C. elegans. To further characterize these antiaging effects and stress resistance, reproductive tests and other aging-related tests were performed. We found that LYG enhanced resistance against oxidative and thermal stress, reproduction, pharynx pumping, motility and growth in N2 wild-type C. elegans. In addition, we analyzed the mechanism for these effects by measuring the activity of superoxide dismutase (SOD) and the expression levels of aging-related genes. We found that LYG enhanced the activities of antioxidant enzymes and upregulated the genes daf-16, sod-3 and sir-2.1, which mediated stress resistance and longevity. In conclusion, LYG had robust and reproducible life-prolonging and antiaging benefits in C. elegans via DAF-16/FOXO regulation.

BackgroundFrailty and cognitive decline are highly prevalent among older adults. However, the relationship between frailty and mild behavioral impairment (MBI), a dementia risk syndrome characterized by later-life emergence of persistent neuropsychiatric symptoms, has yet to be elucidated. We aimed to evaluate the associations between MBI and frailty in older adults without dementia.MethodsIn this cross-sectional study, a consecutive series of 137 older adults without dementia in the Anti-Aging Study, recruited from primary care clinics, were enrolled. Frailty was estimated using the Fried phenotype. MBI was evaluated by the Mild Behavioral Impairment Checklist (MBI-C) at a cut-off point of > 8. Cognition was assessed with the Chinese versions of the Montreal Cognitive Assessment (MoCA-BC) and Mini-mental State Examination (MMSE). Multivariable logistic regression was performed to estimate the relationship between MBI and objective cognition with frailty status.ResultsAt baseline, 30.7% of the older adults had frailty and 18.2% had MBI (MBI+ status). Multivariable logistic regression analysis demonstrated that compared to those without MBI (MBI- status), MBI+ was more likely to have frailty (odds ratio [OR] = 7.44, 95% CI = 1.49–37.21,p = 0.02). Frailty and MBI were both significantly associated with both MMSE and MoCA-BC score (p ConclusionsBoth frailty and MBI status were associated with higher odds of cognitive impairment. MBI was significantly associated with an increased risk of having frailty in the absence of dementia. This association merits further study to identify potential strategies for the early detection, prevention and therapeutic intervention of frailty.

Background: Frailty and cognitive decline are highly prevalent among older adults. However, the relationship between frailty and mild behavioral impairment (MBI), a neurobehavioral syndrome characterized by later-life emergence of sustained neuropsychiatric symptoms, has yet to be elucidated.We aimed to evaluate the associations between mild behavioral impairment and frailty in cognitively normal older adults.Methods: This is a cross-sectional study. A consecutive series of 137 cognitively normal older adults in the Anti-Aging study, recruited from primary care clinics, were enrolled. Frailty was estimated using the original Fried phenotype. MBI was evaluated by the Mild Behavioral Impairment Checklist at a cut-off point of >8 (optimizing sensitivity and specificity), which was developed to assess emergent neuropsychiatric symptoms in accordance with the MBI criteria. Cognition was assessed with the Chinese versions of the Montreal Cognitive Assessment (MoCA-BC) and Mini-mental State Examination (MMSE). Multivariate logistic regression was performed to estimate the relationship between MBI and objective cognition with frailty status.Results: At baseline, 30.6% of the older adults had frailty, 35.0% had prefrailty and 18.2% had MBI (MBI+ status). Multivariate logistic regression analysis demonstrated that compared to MBI- status (without MBI), MBI+ was more likely to have frailty (odds ratio [OR] = 7.44, p = 0.02). The frailty and MBI categories were both significantly associated with both MMSE and MoCA-BC score (pConclusions: Both frailty and MBI status are related to higher risk of cognitive impairment. MBI is significantly associated with an increased risk of having frailty before overt cognitive impairment. This association merits further study to identify strategies to the early detection, prevention and therapeutic intervention of frailty.

Cancer is a complex and refractory disease, which can disseminate from primary site to a different site even at an early stage. Cancer immunotherapy harnesses host immune system to battle against cancer, but only a minority of patients benefit from it. Genetic-based technologies have significantly promoted the development of cancer immunotherapy. Here we describe genetic-based cancer immunotherapies in three aspects: recombinant cancer vaccine, immune checkpoint blockade therapy and adoptive cell transfer. In the future, multi-disciplinary collaboration will greatly increase the scope and effectiveness of cancer immunotherpy.

Traditional Chinese medicine assigns individuals into different categories called “constitutions” to help guide the clinical treatment according to subjective physiologic, psychologic analyses, large-scale clinical observations, and epidemiologic studies. To further explore more objective expressions of constitutions, antibody microarrays were used to analyze the serologic protein profiles of two different constitutions, a balanced (or healthy) constitution (BC) and the dampness constitution (DC) comprising phlegm-dampness and damp-heat constitutions. The profiles of changing constitutions across time were also analyzed. Nineteen differentially expressed proteins between the two groups were identified, with known biologic functions involved in immunity and inflammation. This proteomic study may provide a biologic explanation why the BC is different than the dampness constitution.

Extracellular communication in the tumor microenvironment is critical. Results of qRT-PCR show that circ-0051443 is significantly lower in the plasma exosomes and tissues from patients with hepatocellular carcinoma (HCC) than healthy controls. Compared with the producer cells, circ-0051443 is mainly packaged into exosomes. A receiver operating characteristic curve (ROC) shows that the patients with HCC can be distinguished from the controls by exosomal circ-0051443. The role of exosomal circ-0051443 in HCC was determined by animal and cell analyses. Circ-0051443 is transmitted from normal cells to HCC cells via exosomes and suppresses the malignant biological behaviors by promoting cell apoptosis and arresting the cell cycle. Exosomal circ-0051443 decreases the weight and volume of the xenograft tumors in nude mice via BAK1 upregulation in these tumors. BAK1 expression is mediated by exosomal circ-0051443 through competitive bound to miR-331-3p. Therefore, exosomal circ-0051443 can serve as a predictor and potential therapeutic target for HCC.