Systemic Analgesic Effects of Electroacupuncture in Healthy Individuals: Thermal Threshhold, Acupuncture Sensation Intensity and De-qi on Quantitative Sensory Test.

Background: Electroacupuncture (EA) has been known to exert analgesic effects according to several reports, but studies investigating the analgesic effect of EA using the quantitative sensory test (QST) are rare. Primary Study Objective: To investigate the analgesic effects of electroacupuncture through changes in thermal thresholds measured using the QST. Design: Pilot, randomized, single-blind, parallel design. Setting: The study was conducted at Dongguk University Bundang Oriental Hospital (DUBOH) in South Korea. Participants: We included 40 healthy participants age 20 to 40 years. Intervention: The EA group received EA for 30 minutes at 6 acupuncture points (LI4, PC6, LI10, LI11, ST36, and SP6) and the control group just rested. Outcome measures: The primary outcome measure was 4 thermal thresholds including warm detection (WDT), cold detection (CDT), hot pain (HPT), and cold pain (CPT) measured using QST at baseline and after 15, 30 and 60 minutes. The secondary outcomes were the intensity of acupuncture sensation (visual analogue scale [VAS]) and De-qi (Massachusetts General Hospital Acupuncture Sensation Scale [MASS]). Results: The EA group showed significant changes in HPT (P < .001) and CPT (P = .049) compared with the control group, whereas WDT and CDT did not significantly differ. Furthermore, the changes in thermal thresholds were more pronounced in the higher intensity acupuncture sensation group (VAS ≥40) than in the lower intensity group (VAS < 40), although not significantly. The high De-qi group presented greater changes in WDT, CDT, HPT and CPT than the low De-qi group, as measured using MASS. It was especially statistically significant at HPT a feeling of "heaviness" and "dull pain" and at CDT of "tingling." We observed no adverse events related to the study. Conclusion: The change in thermal pain thresholds effected by EA supports the analgesic effect of EA reported in previous studies. The underlying mechanisms need to be holistically considered, and further studies are needed for definitive evidence.

Nanocarriers for cancer nano-immunotherapy.

The host immune system possesses an intrinsic ability to target and kill cancer cells in a specific and adaptable manner that can be further enhanced by cancer immunotherapy, which aims to train the immune system to boost the antitumor immune response. Several different categories of cancer immunotherapy have emerged as new standard cancer therapies in the clinic, including cancer vaccines, immune checkpoint inhibitors, adoptive T cell therapy, and oncolytic virus therapy. Despite the remarkable survival benefit for a subset of patients, the low response rate and immunotoxicity remain the major challenges for current cancer immunotherapy. Over the last few decades, nanomedicine has been intensively investigated with great enthusiasm, leading to marked advancements in nanoparticle platforms and nanoengineering technology. Advances in nanomedicine and immunotherapy have also led to the emergence of a nascent research field of nano-immunotherapy, which aims to realize the full therapeutic potential of immunotherapy with the aid of nanomedicine. In particular, nanocarriers present an exciting opportunity in immuno-oncology to boost the activity, increase specificity, decrease toxicity, and sustain the antitumor efficacy of immunological agents by potentiating immunostimulatory activity and favorably modulating pharmacological properties. This review discusses the potential of nanocarriers for cancer immunotherapy and introduces preclinical studies designed to improve clinical cancer immunotherapy modalities using nanocarrier-based engineering approaches. It also discusses the potential of nanocarriers to address the challenges currently faced by immuno-oncology as well as the challenges for their translation to clinical applications.

Metal-Based Nanoparticles for Cancer Metalloimmunotherapy.

Although the promise of cancer immunotherapy has been partially fulfilled with the unprecedented clinical success of several immunotherapeutic interventions, some issues, such as limited response rate and immunotoxicity, still remain. Metalloimmunotherapy offers a new form of cancer immunotherapy that utilizes the inherent immunomodulatory features of metal ions to enhance anticancer immune responses. Their versatile functionalities for a multitude of direct and indirect anticancer activities together with their inherent biocompatibility suggest that metal ions can help overcome the current issues associated with cancer immunotherapy. However, metal ions exhibit poor drug-like properties due to their intrinsic physicochemical profiles that impede in vivo pharmacological performance, thus necessitating an effective pharmaceutical formulation strategy to improve their in vivo behavior. Metal-based nanoparticles provide a promising platform technology for reshaping metal ions into more drug-like formulations with nano-enabled engineering approaches. This review provides a general overview of cancer immunotherapy, the immune system and how it works against cancer cells, and the role of metal ions in the host response and immune modulation, as well as the impact of metal ions on the process via the regulation of immune cells. The preclinical studies that have demonstrated the potential of metal-based nanoparticles for cancer metalloimmunotherapy are presented for the representative nanoparticles constructed with manganese, zinc, iron, copper, calcium, and sodium ions. Lastly, the perspectives and future directions of metal-based nanoparticles are discussed, particularly with respect to their clinical applications.

The effectiveness and safety of Wu tou decoction on rheumatoid arthritis: A protocol for systematic review and/or meta-analysis.

BACKGROUND: Rheumatoid arthritis (RA) is one of the common inflammatory diseases with arthritis due to a malfunction of the immune system. The treatments for RA include surgery, physiotherapy, occupational therapies, and medication. The representative treatment is medication and its usage has improved through several guidelines. However, it has some limitations and occurs adverse effects. Meanwhile, traditional Chinese medicine treatments have been used for RA treatment and Wu tou decoction (WTD) is one of them. Regardless of recent studies about WTD's efficacy on RA, there has been no systematic review on this issue. Therefore, this review will focus on the effectiveness and safety of WTD on RA. METHODS: The search for randomized controlled trial about WTD on RA will be performed using multiple electronic databases, manual searches, and the author's e-mail if necessary. According to predefined criteria, randomized controlled trials will be selected and summarization will be performed by the data on study participants, result measurements, interventions, adverse events, and risk of bias. Disease activity score including effective rate, swollen joint count, tender joint count, morning stiffness will be primary outcome measures while blood test about RA including erythrocyte sedimentation rate, C-reactive protein, rheumatoid factors, and adverse events will be secondary outcome measures. We will perform meta-analysis by using Review Manager software, assess the risk of bias by Cochrane Collaboration "risk of bias" tool, and determine the quality of evidence by Grades of Recommendation, Assessment, Development, and Evaluation. RESULTS: This study we will investigate the clinical evidence of the effectiveness and safety of WTD on RA. CONCLUSION: For the RA patients and clinicians, our study will be informative. It can be also a great help for the researchers and policy makers who concentrates on conservative management for RA. TRIAL REGISTRATION NUMBER: INPLASY; INPLASY202220099.

Efficacy and safety evaluation of adjuvant auricular acupuncture for smoking cessation: A study protocol of randomized, assessor-blinded, pragmatic pilot trial.

BACKGROUND: Smoking negatively impacts public health. There are several treatments to quit smoking, and nicotine replacement treatment (NRT) reportedly doubles the smoking cessation rate, with some limitations. Acupuncture is an alternative option with proven effects on smoking cessation. However, there has been no definite report that indicates the efficacy and safety of auricular acupuncture (AA) combined with NRT on smoking cessation. METHODS: This is a randomized, assessor-blind, and pragmatic pilot study. We will recruit 40 participants who want to stop smoking and randomly allocate them into an NRT group and an NRT + AA group with a 1:1 ratio. Participants will receive NRT for 4 weeks and the NRT + AA group will receive additional AA treatment with 5 AA points (Shenmen (TF4), lung (CO14), throat (TF3), inner nose (TG4), and endocrine (CO18)) twice a week for 4 weeks. Follow-up will be conducted 1 and 3 months after intervention completion. The primary outcome will be tobacco consumption and abstinence rate determined by calculating the rate of change in cigarette use and a urine test. Secondary outcomes will be the quality of life (EuroQol-5D and visual analogue scale), nicotine dependence (Fagerstrom test for nicotine dependence), nicotine withdrawal (Minnesota nicotine withdrawal scale), physical effects, satisfaction, and safety measurement (adverse events). RESULTS: We will investigate the efficacy and safety of AA combined with NRT treatment for smoking cessation. CONCLUSION: Our study will provide additional clinical evidence for AA as an adjuvant treatment for smoking cessation. TRIAL REGISTRATION NUMBER: Clinical Research Information Service (registration number: KCT0007212).

Effect of Sacrificial AlN (Aluminum Nitride) Layer on the Deep Surface States of 4H-SiC.

We investigated the effect of a sacrificial AlN layer on the deep energy level states of 4H-SiC surface. The samples with and without AlN layer have been annealed at 1300 °C for 30 minutes duration using a tube furnace. After annealing the samples, the changes of the carbon vacancy (VC) related Z1/2 defect characteristics were analyzed by deep level transient spectroscopy. The trap energy associated with double negative acceptor (VC(2-/0)) appears at ˜0.7 eV and was reduced from ˜0.687 to ˜0.582 eV in the sacrificial AlN layer samples. In addition, the capture cross section was significantly improved from ˜2.1×10-14 to ˜3.8×10-16 cm-2 and the trap concentration was reduced by approximately 40 times.

Culturing at Low Cell Density Delays Cellular Senescence of Human Bone Marrow-Derived Mesenchymal Stem Cells in Long-Term Cultures.

BACKGROUND AND OBJECTIVES: Mesenchymal stem cells (MSCs) have immense therapeutic potential for treating intractable and immune diseases. They also have applications in regenerative medicine in which distinct treatments do not exist. Thus, MSCs are gaining attention as important raw materials in the field of cell therapy. Importantly, the number of MSCs in the bone marrow is limited and they are present only in small quantities. Therefore, mass production of MSCs through long-term culture is necessary to use them in cell therapy. However, MSCs undergo cellular senescence through repeated passages during mass production. In this study, we explored methods to prolong the limited lifetime of MSCs by culturing them with different seeding densities. METHODS AND RESULTS: We observed that in long-term cultures, low-density (LD, 50 cells/cm2) MSCs showed higher population doubling level, leading to greater fold increase, than high-density (HD, 4,000 cells/cm2) MSCs. LD-MSCs suppressed the expression of aging-related genes. We also showed that reactive oxygen species (ROS) were decreased in LD-MSCs compared to that in HD-MSCs. Further, proliferation potential increased when ROS were inhibited in HD-MSCs. CONCLUSIONS: The results in this study suggest that MSC senescence can be delayed and that life span can be extended by controlling cell density in vitro. These results can be used as important data for the mass production of stem cell therapeutic products.

Characterization of a trehalose-degrading enzyme from the hyperthermophilic archaeon Sulfolobus acidocaldarius.

We purified a cytosolic trehalase (TreH) from a thermoacidophilic archaeon Sulfolobus acidocaldarius. Enzyme activity in cell-free extracts indicated that trehalose degradation in the cell occurred via the hydrolytic activity of TreH, and not via TreP (phosphorolytic activity) or TreT (transfer activity). TreH was purified to near-homogeneity by DEAE anion-exchange chromatography, followed by size exclusion and HiTrap Q anion-exchange chromatography, and its molecular mass was estimated as 40 kDa. Maximum activity was observed at 85°C and pH 4.5. The half-life of TreH was 53 and 41 min at 90°C and 95°C, respectively. TreH was highly specific for trehalose and was inhibited by glucose with a Ki of 0.05 mM. Compared with TreH from other trehalases, TreH from S. acidocaldarius is the most thermostable trehalase reported so far. Furthermore, this is the first trehalase characterized in the Archaea domain.

Crystal splitting and enhanced photocatalytic behavior of TiO2 rutile nano-belts induced by dislocations.

Crystal splitting and enhanced photocatalytic activities caused by implied dislocations were observed in hierarchical TiO(2) nano-architectures prepared by one-pot hydrothermal synthesis in concentrated HCl. Microstructural observation revealed that the nanowires formed by continuous splitting of TiO(2) nano-belts, which is caused by a lattice misorientation of about 6°, were generated by an array of dislocations. In addition, the larger amount of dislocations implied in TiO(2) nano-architectures induces higher photocatalytic activities under ultra-violet illumination.