Effects of physical training on depression and related quality of life in pre-frail and frail older adults: a systematic review and meta-analysis.

OBJECTIVES: To investigate the effects of physical training on depression and related quality of life in pre-frail and frail individuals. DESIGN: A systematic review and meta-analysis. PARTICIPANTS: Pre-frail and frail older adults. METHODS: Five electronic databases, including PubMed, Cochrane, Medline, CINAHL, and Wiley were searched through December 2023. Randomized controlled trials (RCT) comparing physical training with usual care, health education, or light-intensity exercise were included. Outcomes included depression and depression-related quality of life. The quality of the included studies was assessed using Physiotherapy Evidence Database (PEDro) score, and the Cochrane Risk of Bias Tool was used to assess the risk of bias. Meta-analysis was performed using the RevMan5.4. The certainty of the evidence was evaluated by The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach. RESULTS: Ten articles with 589 participants met the inclusion criteria and were included. The pooled analysis indicated that depression (SMD = -0.55, 95%CI = -0.92, -0.17, p = 0.004) and mental health status in life (SMD = 1.05, 95%CI = 0.59, 1.50, p < 0.00001) improved significantly in the experimental group. The results of subgroup analysis revealed that the beneficial effects of physical training were significant only in frail older adults but not in pre-frail older adults. CONCLUSION: This meta-analysis showed that the positive effects of physical training on depression and related quality of life were evident for people with frailty. However, no positive results were observed in pre-frail older adults, indicating the need for further investigation in this subgroup.

Isolation and characterizations of multidrug-resistant human cancer cells by a biodegradable nano-sensor.

Multidrug resistance (MDR) remains a significant challenge in cancer therapy, with inherent and acquired resistance distinct. While conventional drug selection processes enable the isolation of cancer cells with acquired multidrug resistance, identifying cancer cells with inherent drug resistance remains challenging. Herein, we proposed a molecular beacon (MB)-based strategy to identify and isolate the inherent MDR cancer cells. A lipid/PLGA core-shell nanoparticulate system (DNCP) was designed to deliver MB for intracellular MDR1 mRNA imaging. DNCP-MB - possess a surface potential of -8 mV and a size of 150 nm - demonstrated effective delivery of MB, remarkable selectivity towards the selected intracellular mRNA targets, and low cytotoxicity. Following DNCP transfection, fluorescence-activated cell sorting (FACS) was employed to differentiate MCF-7 cells into two distinct sub-populations: the Top 10 cells with a high level of MDR gene expression and the Bottom 10 cells with a low level of MDR gene expression, which represent inherent drug-resistant and non-drug-resistant cells, respectively. Intriguingly, we observed a positive correlation between elevated MDR1 mRNA expression and increased migration, enhanced proliferation rate, and tighter spheroid formation. Moreover, we conducted RNA sequencing analysis on the Top 10, Bottom 10, and MCF-7/ADR cells. The findings revealed a notable disparity in the gene ontology enrichment analysis of differentially expressed genes between the Top 10 and Bottom 10 cells when compared to the Bottom 10 and MCF-7/ADR cells. This novel approach provides a promising avenue for isolating inherent drug-resistant cells and holds significant potential in unraveling the mechanisms underlying inherent drug resistance.

Gait performance and prefrontal cortex activation during single and dual task walking in older adults with different cognitive levels.

Background: Growing evidence shows the cognitive function influences the motor performance. The prefrontal cortex (PFC) as a part of the executive locomotor pathway is also important for cognitive function. This study investigated the differences in motor function and brain activity among older adults with different cognitive levels, and examined the significance of cognition on motor functions. Methods: Normal control (NC), individuals with mild cognitive impairment (MCI) or mild dementia (MD) were enrolled in this study. All participants received a comprehensive assessment including cognitive function, motor function, PFC activity during walking, and fear of fall. The assessment of cognitive function included general cognition, attention, executive function, memory, and visuo-spatial. The assessment of motor function included timed up and go (TUG) test, single walking (SW), and cognitive dual task walking (CDW). Results: Individuals with MD had worse SW, CDW and TUG performance as compared to individuals with MCI and NC. These gait and balance performance did not differ significantly between MCI and NC. Motor functions all correlated with general cognition, attention, executive function, memory, and visuo-spatial ability. Attention ability measured by trail making test A (TMT-A) was the best predictor for TUG and gait velocity. There were no significant differences in PFC activity among three groups. Nevertheless, the PFC activated more during CDW as compared with SW in individuals with MCI (p = 0.000), which was not demonstrated in the other two groups. Conclusion: MD demonstrated worse motor function as compared to NC and MCI. The greater PFC activity during CDW in MCI may be considered as a compensatory strategy for maintaining the gait performance. Motor function was related to the cognitive function, and the TMT A was the best predictor for the gait related performance in present study among older adults.

Programmed T cells infiltration into lung metastases with harnessing dendritic cells in cancer immunotherapies by catalytic antigen-capture sponges.

T lymphocytes served as immune surveillance to suppress metastases by physically interacting with cancer cells. Whereas tumor immune privilege and heterogeneity protect immune attack, it limits immune cell infiltration into tumors, especially in invasive metastatic clusters. Here, a catalytic antigen-capture sponge (CAS) containing the catechol-functionalized copper-based metal organic framework (MOF) and chloroquine (CQ) for programming T cells infiltration is reported. The intravenously injected CAS accumulates at the tumor via the folic acid-mediated target and margination effect. In metastases, Fenton-like reaction induced by copper ions of CAS disrupts the intracellular redox potential, i.e., chemodynamic therapy (CDT), thereby reducing glutathione (GSH) levels. Furthermore, CQ helps inhibit autophagy by inducing lysosomal deacidification during CDT. This process leads to the breakdown of self-defense mechanisms, which exacerbates cytotoxicity. The therapies promote the liberation of tumor-associated antigens, such as neoantigens and damage-associated molecular patterns (DAMPs). Subsequently, the catechol groups present on CAS perform as antigen reservoirs and transport the autologous tumor-associated antigens to dendritic cells, resulting in prolonged immune activation. The CAS, which is capable of forming in-situ, serves as an antigen reservoir in CDT-mediated lung metastasis and leads to the accumulation of immune cells in metastatic clusters, thus hindering metastatic tumors.

Programmed antigen capture-harnessed dendritic cells by margination-hitchhiking lung delivery.

Adoptive T cells and immunotherapy suppress the most destructive metastatic tumors and prevent tumor recurrence by inducing T lymphocytes. However, the heterogeneity and immune privilege of invasive metastatic clusters often reduce immune cell infiltration and therapeutic efficacy. Here, the red blood cells (RBC)-hitchhiking mediated lung metastasis delivery of multi-grained iron oxide nanostructures (MIO) programming the antigen capture, dendritic cell harnessing, and T cell recruitment is developed. MIO is assembled to the surface of RBCs by osmotic shock-mediated fusion, and reversible interactions enable the transfer of MIO to pulmonary capillary endothelial cells by intravenous injection by squeezing RBCs at the pulmonary microvessels. RBC-hitchhiking delivery revealed that >65% of MIOs co-localized in tumors rather than normal tissues. In alternating magnetic field (AMF)-mediated magnetic lysis, MIO leads to the release of tumor-associated antigens, namely neoantigens and damage-associated molecular patterns. It also acted as an antigen capture agent-harnessed dendritic cells delivers these antigens to lymph nodes. By utilizing site-specific targeting, erythrocyte hitchhiker-mediated delivery of MIO to lung metastases improves survival and immune responses in mice with metastatic lung tumors.

Effects of strength exercises combined with other training on physical performance in frail older adults: A systematic review and meta-analysis.

OBJECTIVES: Strength training is one of the most important protocols for frailty prevention in the older population. However, effects of adding other types of exercise to strength training in frail older adults remain unknown. Therefore, this review and meta-analysis determined the effects of strength exercise combined with other types of training on physical performance in frail older adults. METHODS: MEDLINE, PubMed, CINAHL, and Cochrane databases were searched through October 2021. In our study, we included both pre-frailty and frailty as frail older adults. The intervention was strength training combined with other exercise training, whereas the control group received usual care or light-intensity exercises. The included studies included at least one of the following outcomes: handgrip strength, knee extensor strength, gait speed, Timed Up and Go, and short physical performance battery. RESULTS: Ten articles met the inclusion criteria and were included. The results indicated that handgrip strength (SMD = 0.86, 95% CI= 0.01-1.70, p = 0.05), knee extensor strength (SMD = 0.61, 95%CI = 0.12-1.10, p = 0.01), TUG (SMD = -1.79, 95%CI = -3.16- -0.43, p=0.01), and SPPB (SMD = 0.53, 95%CI = 0.12-0.94, p = 0.01) improved significantly in the experimental group. CONCLUSIONS: Strength exercise combined with other exercise training improved muscle strength, TUG, and SPPB, but not gait velocity, in frail older adults.

Magnetic nanocomplexes for gene delivery applications.

Gene delivery is an indispensable technique for various biomedical applications such as gene therapy, stem cell engineering and gene editing. Recently, magnetic nanoparticles (MNPs) have received increasing attention for their use in promoting gene delivery efficiency. Under magnetic attraction, gene delivery efficiency using viral or nonviral gene carriers could be universally enhanced. Besides, magnetic nanoparticles could be utilized in magnetic resonance imaging or magnetic hyperthermia therapy, providing extra theranostic opportunities. In this review, recent research integrating MNPs with a viral or nonviral gene vector is summarized from both technical and application perspectives. Applications of MNPs in cutting-edge research technologies, such as biomimetic cell membrane nano-gene carriers, exosome-based gene delivery, cell-based drug delivery systems or CRISPR/Cas9 gene editing, are also discussed.