Deubiquitinating enzyme JOSD2 promotes hepatocellular carcinoma progression through interacting with and inhibiting CTNNB1 degradation.

Although a variety of molecular targets have been identified, hepatocellular carcinoma (HCC) remains among the leading causes of death. As functions of they deubiquitinating enzyme Josephin domain containing 2 (JOSD2) in cancers are still poorly understood, we investigated its function and molecular mechanism in the regulation of HCC progression. Here, we indicated that JOSD2 expression is elevated in patient samples with HCC and positively associated with poor prognosis. Moreover, the promoting roles of JOSD2 in HCC cell survival, migration, and invasion were determined using in vitro models. Importantly, a mechanistic study revealed that JOSD2 binds to and decreases the ubiquitination level of catenin beta 1 (CTNNB1), a key component of Wnt signaling, thereby augmenting Wnt pathway transduction. Furthermore, a series of rescue experiments confirmed the significance of CTNNB1 in the modulation of HCC progression by JOSD2. Our study uncovered JOSD2 as a novel prognostic marker for patients with HCC and identified CTNNB1 as a pivotal partner and downstream target protein of JOSD2, which may aid in the development of JOSD2 as a promising molecular target for HCC treatment.

A cross-sectional study on associations of physical symptoms, health self-efficacy, and suicidal ideation among Chinese hospitalized cancer patients.

BACKGROUND: Epidemiological studies have shown increased risk of suicide in cancer patients compared with the general population. The present study aimed to examine the association between physical symptoms and suicidal ideation in Chinese hospitalized cancer patients and test the modifying effect of health self-efficacy on the association. METHODS: A cross-sectional study was conducted with 544 hospitalized cancer patients in two general hospitals in northeast China via face-to-face interviews. Suicidal ideation was measured by using the first four items on the Yale Evaluation of Suicidality scale and then dichotomized into a positive and negative score. Multivariate logistic regression analyses were conducted to examine the impacts of physical symptoms, health self-efficacy, and their interactions on suicidal ideation. RESULTS: The suicidal ideation rate was 26.3% in the enrolled cancer patients. Logistic regression showed that insomnia (aOR = 1.84, 95% CI 1.13 to 3.00, p = 0.015) and lack of appetite (aOR = 2.14, 95% CI 1.26 to 3.64, p = 0.005) were significantly associated with suicidal ideation. Low health self-efficacy had a marginally significant exaggerating effect on the association between pain and suicidal ideation (aOR = 2.77, 95% CI 0.99 to 7.74, p = 0.053), after adjusting for significant socio-demographics, clinical characteristics, and depression. CONCLUSIONS: These findings demonstrate significant associations between physical symptoms (insomnia and/or lack of appetite) and suicidal ideation and highlight the potential modifying role of health self-efficacy in the identification and prevention of suicide among cancer patients.

DNAM1 and 2B4 Costimulatory Domains Enhance the Cytotoxicity of Anti-GPC3 Chimeric Antigen Receptor-Modified Natural Killer Cells Against Hepatocellular Cancer Cells in vitro.

PURPOSE: Hepatocellular cancer (HCC) is the sixth most prevalent cancer and the third leading cause of cancer-related death worldwide. Cellular immunotherapy against glypican 3 (GPC3) has recently been used in the treatment of HCC, following the success of chimeric antigen receptor (CAR)-T therapy in treatment of B cell malignancy. However, CAR-T cells are not "off-the-shelf" and always cause cytokine release syndrome, which can be eliminated by using natural killer (NK) cells as effector cells. Since a costimulatory signal is necessary for the activation, persistence, or cytotoxicity of CAR-T cells, we speculated that the costimulatory signal is also required for CAR-NK cells in HCC treatment. METHODS: Five anti-GPC3 CAR plasmids containing different costimulatory domains were constructed. They included Z (only the CD3ζ domain, no costimulatory domain), CD28.Z (T-cell costimulatory domain CD28), DNAM1/2B4.Z (NK-cell-associated costimulatory domain DNAM1 or 2B4), and DNAM1.2B4.Z (both NK-cell-associated costimulatory domains). Respective CAR-NK-92 cells were generated. The MTT viability assay was performed to evaluate the effect of the different costimulatory domains on CAR-NK-cell proliferation. The effect on persistence was analyzed using an apoptosis assay and flow cytometry. Special cytotoxicity against normal hepatocellular cells and GPC3+ malignant cells was investigated in vitro. The concentration of cytokines (TNF-α and IFN-γ) released by CAR-NK-92 cells was also measured by ELISA. RESULTS: NK-cell-associated costimulatory signal was necessary for CAR-NK-92 cells. CAR-NK-92 cells with DNAM1 and/or 2B4 expanded more quickly and persisted with a lower apoptotic ratio, compared to the presence of CD28 or no costimulatory signal. All CAR-NK-92 cells showed special cellular cytotoxicity in vitro. CAR-NK-92 cells with NK-cell-associated costimulatory domains exhibited higher cytotoxic ability compared with those without any costimulatory domain or with T-cell costimulatory domain. CAR-NK-92 cells with both DNAM1 and 2B4 displayed the highest cytotoxicity. The cytokine release assay results were consistent with those of the cytotoxicity assay. CONCLUSION: We provided the first evidence supporting a strategy using DNAM1 and 2B4 costimulatory domains to generate anti-GPC3 CAR-NK-92 cells, which exhibits enhanced cytotoxicity against hepatocellular cancer cells in vitro.

Cumulative incidence of suicidal ideation and associated factors among adults living in temporary housing during the three years after the Great East Japan Earthquake.

BACKGROUND: The effect of disasters on suicidality is not known. We aimed to retrospectively determine the cumulative incidence of suicidal ideation during the 3 years after the Great East Japan Earthquake among residents in temporary housing without prior suicidal ideation, as compared to the general population. Moreover, we aimed to identify the risk factors for the onset of suicidal ideation. METHODS: A cross-sectional survey involving face-to-face interviews was conducted 3 years after the earthquake with adult community residents in disaster-affected areas and a control area using the World Health Organization Composite International Diagnostic Interview version 3.0. We compared the cumulative incidence of suicidal ideation between the two areas using the Cox proportional hazard model and examined risk factors for the onset of suicidal ideation using a multiple logistic regression analysis. RESULTS: Among 1019 respondents in the disaster-affected areas, the cumulative incidence of suicidal ideation over 1, 2, and 3 years after the earthquake was 1.4%, 2.4%, and 2.8%, respectively, which was significantly higher than that in the control area. Not being married, being injured in the disaster, and poor subjective physical health were associated with the onset of suicidal ideation. LIMITATIONS: We estimated the time of onset of suicidal ideation based on the respondents' current age and self-reported onset age, which limits the accuracy of the onset timing. CONCLUSIONS: We revealed a higher incidence of suicidal ideation in temporary housing residents and identified several risk factors, which suggests the importance of developing countermeasures to prevent suicide after a disaster.

Life cycle of meats: an opportunity to abate the greenhouse gas emission from meat industry in Japan.

The food industry is one of the world's largest industrial sectors, hence a large contributor of greenhouse gases (GHG) which cause global warming. This study evaluates the life cycle of various types of meat to determine if the GHG emission from the meat industry in Japan could be reduced if the population makes different dietary choices. It was confirmed that the GHG emission of beef was greater than that of pork or chicken. The GHG emission from meat in general also depends on the per capita caloric intake (if meat supplies the recommended animal protein or contributes to it at the present rate). In a healthy and balanced diet (9.2 MJ i.e., 2200 kcal in total, where either mixed meat or chicken or pork or beef contributes 2.2%), the GHG emission is estimated to be 0.28 or 0.17 or 0.15 or 0.77 kg CO2 eq/person/day, respectively. A change in consumption patterns (from beef to chicken or pork) and the adoption of a healthy and balanced diet would help to abate about 2.5-54.0 million tons (CO2 eq) produced by the meat industry each year in Japan.

Biosurfactants for microbubble preparation and application.

Biosurfactants can be classified by their chemical composition and their origin. This review briefly describes various classes of biosurfactants based on their origin and introduces a few of the most widely used biosurfactants. The current status and future trends in biosurfactant production are discussed, with an emphasis on those derived from plants. Following a brief introduction of the properties of microbubbles, recent progress in the application of microbubble technology to molecular imaging, wastewater treatment, and aerobic fermentation are presented. Several studies on the preparation, characterization and applications of biosurfactant-based microbubbles are reviewed.

Characterization of a soybean oil-based biosurfactant and evaluation of its ability to form microbubbles.

This paper characterizes the physico-chemical properties of the soybean oil-based polymeric surfactant, Palozengs R-004 (hereafter referred to as R-004). The surface activity of R-004 is comparable to the reported activities of biosurfactants produced by microorganisms and higher than some of the conventional synthetic surfactants. The surface tension of Milli-Q water was reduced to a minimum value of roughly 30mN/m at a concentration of about 0.07wt.%. R-004 exhibited a unique aggregation behavior: small aggregates (pre-micelles) were formed at very low concentrations. Zeta-potential measurements showed that the micelles of R-004 are negatively charged due to the presence of carboxylic groups. The ability of R-004 to form and stabilize microbubbles was evaluated and was found to be greatly affected by filtration while remaining independent of R-004 concentration over the concentration range studied (0.05-0.5wt.%). These results suggest that a very low level of surfactant can be used to produce microbubbles without affecting their properties. Our results suggest the possibility of using soybean oil-based surfactants to food, pharmaceutical, and cosmetic applications.

Effects of surfactant and electrolyte concentrations on bubble formation and stabilization.

As interest in the application of microbubbles grows, it is becoming increasingly important to understand the factors affecting their formation and properties in order to effectively generate microbubbles. This paper investigates the effect of surfactant concentration and electrolyte addition on the size distribution and stability of microbubbles. The anionic surfactant sodium dodecyl sulfate (SDS) was used as the surfactant. Minimum bubble diameter and maximum stability were achieved at surfactant concentrations above the CMC. The effect of the electrolyte addition was studied by adding sodium chloride (NaCl) at an SDS concentration below the critical micelle concentration (CMC). Addition of NaCl decreased bubble size and improved bubble preparation to a certain extent. The addition of salt at low concentrations did not affect the surface tension; however, the surface tension was reduced as salt concentration was increased and reached a constant value for NaCl concentrations above 0.25%. The presence of NaCl resulted in a significant decrease in zeta-potential, implying a reduction in the surface charge of SDS micelles. This result suggests that the presence of NaCl may improve the generation and stability of bubbles by enhancing the structures of the adsorption monolayer and interfacial film.

Atomic force microscopy study of chromosome surface structure changed by protein extraction.

We applied atomic force microscopy (AFM) to investigate the surface structure of barley chromosome in combination with a chemical treatment method. As a result, we have obtained high-resolution topographic images of granular structures with a diameter of ca. 50 nm on the surface of critical-point dried metaphase chromosomes. Treatment with 2M NaCl significantly modified the chromosome surface structure: surface roughness was increased and chromosome thickness was decreased. The NaCl treatment extracted two major proteins with molecular weights of 4000 and 20,000 Da. These proteins might be belonging to non-histone protein families that do not contain any aromatic amino acid. The results demonstrate the advantage of the combined method of high-resolution AFM imaging and chemical treatments for understanding nano-scale surface structures of the chromosome.