Immunomodulatory effects of exercise in cancer prevention and adjuvant therapy: a narrative review.

Successful application of cancer immunotherapy has rekindled hope in cancer patients. However, a number of patients are unresponsive to immunotherapy and related treatments. This unresponsiveness in cancer patients toward different treatment regimens can be mainly attributed to severe immune dysfunction in such patients. Several reports indicate that physical exercise can significantly lead to improved cancer patient outcomes. Since exercise gets immense response from the immune system, it can be utilized to improve immune function. Leukocytes with enhanced functions are substantially mobilized into the circulation by a single bout of intense physical exercise. Chronic physical exercise results in greater muscle endurance and strength and improved cardiorespiratory function. This exercise regime is also useful in improving T-cell abundance and reducing dysfunctional T cells. The current available data strongly justify for future clinical trials to investigate physical exercise use as an adjuvant in cancer therapy; however, optimal parameters using exercise for a defined outcome are yet to be established. The components of the immune system associate with almost every tumorigenesis step. The inter-relationship between inflammation, cancer, and innate immunity has recently gained acceptance; however, the underlying cellular and molecular mechanisms behind this relationship are yet to be solved. Several studies suggest physical exercise-mediated induction of immune cells to elicit anti-tumorigenic effects. This indicates the potential of exercising in modulating the behavior of immune cells to inhibit tumor progression. However, further mechanistic details behind physical exercise-driven immunomodulation and anticancer effects have to be determined. This review aims to summarize and discuss the association between physical exercise and immune function modulation and the potential of exercise as an adjuvant therapy in cancer prevention and treatment.

Designable Layer Edge States in Quasi-2D Perovskites Induced by Femtosecond Pulse Laser.

The low-energy layer edge states (LESs) from quasi 2D hybrid perovskite single crystals have shown great potential because of their nontrivial photoelectrical properties. However, the underlying formation mechanism of the LESs still remains controversial. Also, the presence or creation of the LESs is of high randomness due to the lack of proper techniques to manually generate these LESs. Herein, using a single crystals platform of quasi-2D (BA)2 (MA)n-1 Pbn I3n+1 (n > 1) perovskites, the femtosecond laser ablation approach to design and write the LESs with a high spatial resolution is reported. Fundamentally, these LESs are of smaller bandgap 3D MAPbI3 nanocrystals which are formed by the laser-induced BA escaping from the lattice and thus the lattice shrinkage from quasi-2D to 3D structures. Furthermore, by covering the crystal with tape, an additional high-energy emission state corresponding to the reformation of (BA)2 PbI4 (n = 1) within the irradiation region is generated. This work presents a simple and efficient protocol to manually write LESs on single crystals and thus lays the foundation for utilizing these LESs to further enhance the performance of future photoelectronic devices.

Cucurbitacin E inhibits cellular proliferation and induces apoptosis in melanoma by suppressing HSDL2 expression.

BACKGROUND: Melanoma is among the most aggressive types of skin malignancy and can have an unpredictable clinical course. Exploration of novel therapeutic targets and their regulators remains essential for the prevention and treatment of melanoma. METHODS: HSDL2 protein levels were examined by immunohistochemistry. The roles of HSDL2 in cell proliferation and apoptosis were identified by CCK-8 and colony formation assays. The function of HSDL2 in cell apoptosis was analysed by flow cytometry. Western blotting, cell proliferation and apoptosis and a xenograft tumour model were utilized to explore the inhibitory functions and mechanisms of CuE in melanoma. RESULTS: HSDL2 is overexpressed in melanoma and promotes melanoma progression by activating the ERK and AKT pathways. CuE could inhibit the ERK and AKT pathways by decreasing HSDL2 expression; therefore, CuE could inhibit melanoma growth in vitro and in vivo. CONCLUSION: HSDL2 may be a promising therapeutic target against melanoma, and CuE can inhibit melanoma by downregulating HSDL2 expression.

Quantitative Design of Bright Fluorophores and AIEgens by the Accurate Prediction of Twisted Intramolecular Charge Transfer (TICT).

Inhibition of TICT can significantly increase the brightness of fluorescent materials. Accurate prediction of TICT is thus critical for the quantitative design of high-performance fluorophores and AIEgens. TICT of 14 types of popular organic fluorophores were modeled with time-dependent density functional theory (TD-DFT). A reliable and generalizable computational approach for modeling TICT formations was established. To demonstrate the prediction power of our approach, we quantitatively designed a boron dipyrromethene (BODIPY)-based AIEgen which exhibits (almost) barrierless TICT rotations in monomers. Subsequent experiments validated our molecular design and showed that the aggregation of this compound turns on bright emissions with ca. 27-fold fluorescence enhancement, as TICT formation is inhibited in molecular aggregates.

Effectiveness of telemonitoring versus usual care for chronic obstructive pulmonary disease: A systematic review and meta-analysis.

AIMS: The purpose of this research was to investigate the effectiveness of telemonitoring for chronic obstructive pulmonary disease. METHODS: We searched MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials and CINAHL up to September 2018. We selected randomised controlled trials comparing telemonitoring and control groups for chronic obstructive pulmonary disease management. Two reviewers independently examined articles based on eligibility, extracted data and evaluated the risk of bias. The Cochrane tool was applied for assessing the risk of bias. The 95% confidence interval was calculated. RESULTS: A total of 28 randomised controlled trials were included. Meta-analysis revealed that there were no variables showing a statistically significant difference between telemonitoring and control groups. Chronic obstructive pulmonary disease exacerbation rate (six studies) was not different between two groups (risk ratio 0.67, 95% confidence interval 0.31-1.42). Subgroup analysis showed that telemonitoring reduced exacerbation rates when the intervention continued for longer than six months or pulmonary function was monitored. No differences between groups were noticed for mortality (seven studies, risk ratio 0.89, 95% confidence interval 0.60-1.34). Similarly, no differences between groups were observed in the patient-reported outcomes (St George's Respiratory Questionnaire, Chronic Respiratory Disease Questionnaire-Dyspnea score) and for health service utilization (length of hospital stay, number of hospital admissions, number of emergency room visits). CONCLUSIONS: Telemonitoring for chronic obstructive pulmonary disease was unlikely to result in statistically significant improvements in health outcomes. However, our novel finding was that at least six months of intervention duration and monitoring of pulmonary function play roles in activating the effects of telemonitoring.

Acute Cerebral Infarction in a Patient with Persistent Trigeminal Artery and Homolateral Hypoplasia of Internal Carotid Artery Distal Anastomosis: A Case Report and a Mini Review of the Literature.

BACKGROUND: Persistent primitive trigeminal artery (PPTA) is a rare remnant between the internal carotid artery (ICA) and the basilar artery into adulthood. PPTA generally lacks specific clinical manifestations and occasionally accompanies with other cerebrovascular diseases. CASE PRESENTATION: We reported a 48-year-old Chinese woman who had repeated episodes of transient ischemic attack presented to our hospital. She had no related risk factors of ischemic cerebrovascular diseases. Magnetic resonance image findings demonstrated acute cerebral infraction in centrum semiovale. Magnetic resonance angiography findings indicated right PPTA and ipsilateral hypoplasia of ICA distal anastomosis. CONCLUSIONS: To the best of our knowledge, this is the first report that acute cerebral infarction in a patient with the right PPTA and ipsilateral hypoplasia of ICA distal anastomosis. According to the literature, congenital factor may play an important role in the formation of these vascular anomalies.

Current status of endoscopic submucosal dissection for early gastric cancer in Korea: role and benefits.

BACKGROUND/AIMS: This study was aimed to investigate the current clinical status of endoscopic submucosal dissection (ESD) for early gastric cancer (EGC) in Korea based on a National Health Insurance (NHI) database between 2011 and 2014. METHODS: The claims data of ESD for EGC in Korean NHI were reviewed using material codes of Health Insurance Review and Assessment Service between November 2011 and December 2014. The current clinical status was analyzed in terms of treatment pattern, in-hospital length of stay (LOS), total medical costs, and en bloc resection rate according to the hospital type. RESULTS: A total of 23,828 cases of ESD for EGC were evaluated. ESD was performed in 67.4% of cases in tertiary care hospitals, 31.8% in general hospitals, and 0.8% in hospitals, respectively. The median LOS was 5 days, and total median medical costs was approximately 1,300 US dollars. En bloc resection rate was 99%; 8.5% of cases underwent additional treatment within 90 days ESD, and 5.5% in 91 to 365 days after ESD. The clinical status was not significantly different according to the year and hospital type. CONCLUSION: A majority of ESD for EGC were performed in tertiary care hospitals in Korea. The clinical status showed excellent clinical outcomes and did not differ by the year and between the types of hospitals in Korea.

Simultaneous Imaging and Selective Photothermal Therapy through Aptamer-Driven Au Nanosphere Clustering.

Gold (Au) nanoparticles display enhanced near-infrared (NIR) photothermal effects upon the formation of clusters. We studied the photothermal properties of Au nanosphere clusters on the single-particle level using photothermal heterodyne imaging (PTHI) microscopy to understand the enhancement mechanisms. NIR photothermal responses of Au nanoparticle clusters were found to significantly increase from monomers to trimers. The averaged PTHI signal intensity of Au nanosphere dimers and trimers is ∼10 and ∼25 times that of monomers. The NIR photothermal effect of clustered nanospheres strongly correlates with their longitudinal plasmon mode. Clustered Au nanospheres were demonstrated to exhibit dual-capability NIR photothermal imaging and therapy of human prostate cancer cells with high efficiency and selectivity. This strategy can be potentially utilized for simultaneous cancer imaging and therapy with 3D selectivity.

Long-Term Clinical Outcomes of Endoscopic Submucosal Dissection in Patients with Early Gastric Cancer: A Prospective Multicenter Cohort Study.

Background/Aims: Endoscopic submucosal dissection (ESD) has been regarded as a curative treatment for early gastric cancer (EGC) in indicated cases. The aim of this study was to evaluate the nationwide long-term clinical outcomes of ESD for EGC in Korea. Methods: A prospective multicenter cohort study was performed to evaluate the long-term efficacy of ESD for EGC within pre-defined indications at 12 institutes in Korea. The cases that met the expanded criteria upon pathological review after ESD were followed for 5 years. The primary outcome was 5-year disease specific free survival. Results: Six hundred ninety-seven patients with 722 EGCs treated with ESD were prospectively enrolled and followed for 5 years. Complete resection was achieved in 81.3% of the cases, and curative resection was achieved in 86.1%. During the 5-year follow-up, the overall survival rate was 96.6%, and the disease specific free survival rate was 90.6%. Local recurrence developed in 0.9%, and metachronous tumor development occurred in 7.8%; both conditions were treated by endoscopic or surgical treatment. Distant metastasis developed in 0.5% during follow-up. Conclusions: ESD showed excellent long-term clinical outcomes and can be accepted as a curative treatment for patients with EGC who meet the expanded criteria in final pathology studies.

Protection of prenylated flavonoids from Mori Cortex Radicis (Moraceae) against nitric oxide-induced cell death in neuroblastoma SH-SY5Y cells.

Seven prenylated flavanoids, licoflavone C (1), cyclomulberrin (2), neocyclomorusin (3), sanggenon I (4), morusin (5), kuwanon U (6) and kuwanon E (7), and three 2-arylbenzofurans, moracin P (8), moracin O (9), and mulberrofuran Q (10) were isolated from the MeOH extract of Mori Cortex Radicis. Among these, compounds 2-7 enhanced cell viability in a dose-dependent manner against sodium nitroprusside-induced cell death in neuroblastoma SH-SY5Y cells, which was measured by MTT reduction assay (EC(50) values of 4.4, 5.6, 8.0, 6.4, 8.7, and 11.9 µg/mL, respectively). Among 10 compounds, C-3 prenylated flavones (2, 3, and 5) and prenylated flavanones (4, 6, and 7) showed cell protection. However, compound 1 which lacks the prenyl group at C-3 and three 2-arylbenzofurans (8-10) did not show protective effect. The order of cell protection was as follow: C-3 prenylated flavones (2, 3, and 5) > prenylated flavanones (4, 6, and 7) > 2-arylbenzofurans (8-10) and flavone (1). From this result, we show that some prenylated flavones and flavanones might protect neuronal cells against nitrosative stress-mediated cell death. Even though further evaluations are necessary in vitro and in vivo study, we carefully suggest that some prenylated flavonoids from Mori Cortex Radicis might protect neuronal cells from neurodegenerative diseases.

Inhibitory effect of 2-arylbenzofurans from the Mori Cortex Radicis (Moraceae) on oxygen glucose deprivation (OGD)-induced cell death of SH-SY5Y cells.

Three known 2-arylbenzofurans, moracin P (1), moracin O (2) and mulberrofuran Q (3) were isolated from the MeOH extract of the Mori Cortex Radicis. These compounds 1-3 enhanced cell viability in dose-dependent manner against oxygen-glucose deprivation (OGD)-induced cell death in neuroblastoma SH-SY5Y cells, which was measured by MTT reduction assay. (EC(50) values of 10.4, 12.6, and 15.9 µM, respectively). In addition, the compounds 1-3 were examined for their inhibitory effect on OGD-induced ROS production by FACS analysis. We observed these compounds reduced ROS production in OGD-induced cell death (IC(50) values of 1.9, 0.3 and 12.1 µM, respectively). Consequently, reactive oxygen species (ROS) were overexpressed in OGD-induced cells and all three compounds reduced ROS induced by OGD in dosedependent manner. Taken together, compounds 1-3 might protect neuronal cell death against the oxidative stress induced by OGD, though further studies in vitro and in vivo models are necessary.