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Preventing disease and maintaining the health of the elderly are crucial goals for an aging population, with obesity and immune function restoration being of paramount importance. Obesity, particularly visceral obesity characterized by excessive fat accumulation around the abdominal organs, is linked to chronic conditions such as diabetes, hypertension, cardiovascular diseases, and immune dysfunction. Globally, obesity is considered a disease, prompting significant research interest in its treatment. Therefore, it is essential to explore potential therapeutic and preventive strategies to address obesity and the decline in immune function brought about by aging. Tenebrio molitor larvae (TML), commonly known as ‘mealworms,’ are rich in unsaturated fatty acids, including oleic and linoleic acids, and essential amino acids, such as isoleucine and tyrosine. In this study, we aimed to investigate the effects of the consumption of TML oil and mealworm fermented extract (MWF-1) on obesity and immunological changes in aged obese mice. Our data showed reduced body fat in 23-week-old C57BL/6 mice fed processed TML products for 6 weeks. Additionally, the characteristically high levels of serum triglycerides decreased by treating with TML oil. The immune responsiveness results confirmed an increase in B cells by treating with MWF-1, while cytokine levels (interferon-gamma, tumor necrosis factor-alpha, interleukin-2, and −6) were restored to levels similar to young mice. These results suggest that TML oil and MWF-1 are promising dietary supplements for addressing obesity and restoring immune function.

Abstract Introduction Benzo[a]pyrene (BaP) is a toxic polycyclic aromatic hydrocarbon known as an exogenous AhR ligand. This study investigates the role of BaP in inducing immune checkpoint expression in lung adenocarcinoma (LUAD) and the underlying mechanisms involving the aryl hydrocarbon receptor (AhR) and tryptophan (Trp) metabolism. Methods We assessed the expression of immune checkpoint molecules, including PD-L1 and ICOSL, in lung epithelial cell lines (BEAS-2B and H1975) exposed to BaP. The involvement of AhR in BaP-induced immune checkpoint expression was examined using AhR silencing (siAhR). Additionally, the role of Trp metabolism in BaP-mediated immune evasion was explored through culturing in Trp (-/+) condition media, treatments with the inhibitors of rate-limiting enzymes in Trp metabolism (TDO2 and IDO1) and analyses of Trp-catabolizing enzymes. The therapeutic potential of targeting Trp metabolism, specifically TDO2, was evaluated in vivo using C57BL/6 mice orthotopically inoculated with LUAD cells. Results BaP exposure significantly upregulated the mRNA and surface expression of PD-L1 and ICOSL, with AhR playing a crucial role in this induction. Trp metabolism was found to enhance BaP-mediated immune evasion, as indicated by stronger induction of immune checkpoints in Trp (+) media and the upregulation of Trp-catabolizing enzymes. TDO2 inhibition markedly suppressed the surface expression of PD-L1 and ICOSL, demonstrating the importance of Trp metabolism in BaP-induced immune evasion. Further analysis confirmed the high TDO2 expression in lung adenocarcinoma and its association with poor patient survival. Using an orthotopic implantation mouse model, we demonstrated the inhibitory effect of two different TDO2 inhibitors on tumorigenesis, immune checkpoints, and tryptophan metabolism. Conclusions This study highlights the key mechanisms behind BaP-induced immune evasion in LUAD, particularly through the TDO2/AhR axis. It reveals how TDO2 inhibitors can counteract immune checkpoint activation and boost anti-tumor immunity, suggesting new paths for targeted lung cancer immunotherapy. The findings significantly improve our understanding of immune evasion in LUAD and underscore the therapeutic promise of TDO2 inhibition.

Inducing programmed cell death in tumors is a fundamental approach in cancer therapy, prompting extensive efforts to discover bioactive compounds with anticancer properties. Peucedanum japonicum, a plant used in traditional medicine across East Asia, has been reported to exhibit various biological activities, including anticancer effects. This study aimed to evaluate the apoptosis-inducing effects of methanol/dichloromethane (MeOH/CH2Cl2) extracts of P. japonicum roots and their components in HL-60 human leukemia cells. Compounds were isolated using solvent extraction and reverse-phase column chromatography, and their structures were confirmed by nuclear magnetic resonance (NMR) spectroscopy. The cytotoxicity effect of the compounds was tested on various cancer cell lines (HL-60, A549, and MCF-7). Two coumarins, (−)-isosamidin (1) and 3′S,4′S-disenecioylkhellactone (2), were isolated through bioactivity-guided fractionation. Compound 2 significantly induced apoptosis in HL-60 cells, as evidenced by an increase in the sub-G1 cell population and the initiation of both early and late apoptosis. Additional apoptotic markers, including reduced mitochondrial membrane potential (MMP) and increased cleavage of caspase-3, -8, and -9, were observed. These findings suggest that compound 2 shows potential as a candidate for leukemia treatment, providing a promising natural-product-based approach to cancer therapy.

Although titanium-based metal implants have become a game changer in dental and orthopedic therapies, they still have several problems such as late osseointegration and immune response. In this study, we present a novel strategy to develop Ti6Al4V-based implants embedded with biogenic hydroxyapatite derived from equine bone to overcome these problems. A selective laser melting technique was employed for facile fabrication with flexible fusing feedstock and regular uniform distribution of equine bone. The physicochemical characteristics, cell attachment and proliferation, osteogenic differentiation, osseointegration, inflammatory response, and metabolomics of the developed Ti6Al4V/equine bone composite were then investigated. The Ti6Al4V-based composite integrated with equine bone at a certain concentration has improved the crystalline structure (β-Ti) suitable for implantation and exhibited higher hydrophilicity and protein adsorption. They significantly promoted cell attachment, osteogenic differentiation, and anti-inflammatory effects in vitro. In vivo study confirmed the osseointegration and alleviated inflammatory responses. Furthermore, the Ti6Al4V-based implants integrated with equine bone significantly reduced metabolites associated with inflammatory responses both in vitro and in vivo. The observed reduction in inflammatory responses suggests a subsequent promotion of osteogenesis. These promising results position the Ti6Al4V-based implant integrated with equine bone as a potential candidate for replacing conventional dental and orthopedic implants.

The development of efficient biomarkers and probes for monitoring and treating cancer, specifically metastatic cancer, is a critical research area that can have a significant impact on both patient outcomes and drug discovery. In this context, TiNIR has been developed to detect tumor-initiating cells (TICs), with heme oxygenase 2 (HO2) as a promising therapeutic biomarker for tumor-initiating cells. In this study, TiNIR has demonstrated its effectiveness as an in vivo metastatic lung cancer tracker, highlighting its potential as a valuable tool in cancer research and therapy. The development of innovative approaches that selectively target metastatic cancers represents a promising avenue for improving survival rates and enhancing the quality of life of cancer patients.

Studying the specific roles of macrophage subsets has been hampered by a lack of subset-specific probes. Here the authors report an M1 selective fluorescent probe named CDr17, and demonstrate the suitability of this probe for tracking M1 macrophages in vivo.

In this paper, we address the problem of joint transmit beamforming and power control for a multiuser multiple-input single-output (MISO) indoor optical downlink channel. We adopt a shot-noise limited Poisson channel with transmitting signals subject to average and peak transmits power constraints. To minimize the total transmit power, we formulate an optimal downlink beamforming problem using convex optimization method via second-order cone programming techniques. In our approach, the total transmit power is optimized subject to the signal-to-interference-plus-noise ratio (SINR). The results verify performance improvements of the proposed technique as compared to conventional multiuser MISO indoor optical systems.

Ginseng is a traditional medicine with health benefits for humans. Protopanaxadiol (PPD) is an important bioactive compound found in ginseng. Transgenic rice containing PPD has been generated previously. In the present study, extracts of this transgenic rice were evaluated to assess their antiadipogenic and anti-inflammatory activities. During adipogenesis, cells were treated with transgenic rice seed extracts. The results revealed that the concentrations of the rice seed extracts tested in this study did not affect cell viability at 3 days post-treatment. However, the rice seed extracts significantly reduced the accumulation of lipids in cells and suppressed the activation of CCAAT/enhancer-binding protein α (C/EBPα) and peroxisome proliferator-activated receptor γ (PPARγ), which in turn inhibited the expression of adipogenesis-related mRNAs, such as adiponectin, PPARγ, C/EBPα, sterol regulatory element-binding protein 1, glucose transport member 4, and fatty acid synthase. In adipocytes, the extracts significantly reduced the mRNA expression of inflammation-related factors following LPS treatment. The activation of NF-κB p65 and ERK 1/2 was inhibited in extract-treated adipocytes. Moreover, treatment with extract #8 markedly reduced the cell population of the G2/M phase. Collectively, these results indicate that transgenic rice containing PPD may act as an obesity-reducing and/or -preventing agent.

Attempts to image activated macrophages in vivo have been hampered by selectivity and delivery problems. Here the authors develop a small molecule fluorescent probe specific to activated M1 and M2 macrophages, identify the orphan receptor Slc18b1/SLC18B1 as the mechanism of uptake, and use it to image atherosclerosis in mice.

The skin is a very suitable organ for the induction of immune responses to vaccine antigens. Antigen delivery systems to the skin by needle and syringe directly deposit the antigen into the epidermal-dermal compartment, one of the most immunocompetent sites due to the presence of professional antigen-presenting cells aimed at the induction of antigen-specific T cells. In this study, we analyzed the amount of ovalbumin as an antigen delivered to the skin by a microneedle. When ovalbumin protein as an antigen was delivered to the skin of mice using a dissolving microneedle, it induced an immune response through the enhanced proliferation and cytokines production by the splenocytes and lymph nodes. Also, it effectively increased the ovalbumin-specific CD8+ T cell and CD4+ T cell population and induced an ovalbumin-specific CTL response against the graft of ovalbumin-expressing EG7 tumor cells in the immunized mice. Also, we identified the inhibition of tumor growth and prevention of tumor formation in the context of the therapeutic and prophylactic vaccine, respectively through EG-7 tumor mouse model. Finally, these data show the potential of patches as attractive antigen delivery vehicles.

Here we examine the effects of extracts of Poria cocos mycelium fermented with freeze-dried plum powder (PPE) on the α-melanocyte stimulating hormone (α-MSH)-stimulated melanogenesis in cultured murine B16 melanoma cells (B16 cells), relative to the effects of Prunus extract. We found that an extract of Prunus fermentation showed significant inhibition of melanogenesis and tyrosinase activity with no effect on cell proliferation and was more active compared to Prunus extract alone. Furthermore, we confirmed that medium containing 3% Prunus was the optimal culture substrate for fermentation with Poria cocos. These results provide evidence that Prunus fermentation extract affects skin whiting in murine B16 melanoma cells (B16 cells). Prunus contains rutin, oxalic acid, succinic acid, and fumaric acid, which help in digestion and fatigue recovery. The rutin of Prunus mume is reported to have antioxidant and anti-inflammatory effects. Also, Prunus extract has a tyrosinase inhibitory activity for skin whiting through its antioxidant activity. Therefore, we believe the Prunus extract for Poria cocos fermentation can be provided as a potential mediator to induce skin whiting.

We propose a model that elucidates the two channels through which alternative marketing arrangements affect spot price in livestock markets. The direct effect works through their effect on demand and supply. The indirect effect works through spot price volatility, which has been ignored in the literature. We then estimate a dynamic model with data from the U.S. hog market to test our model implications and quantify the two effects. We find increases in the use of AMAs increase spot price volatility and decrease spot price level. The short-run effects are small but the long-run effects are nontrivial.

Lectins are carbohydrate-binding proteins with various biological activities, such as antitumor and immunomodulatory effects. Although lectins have various biological activities, they are still limited by cytotoxicity in normal cells. To overcome this problem, we used the noncytotoxic part of Korean mistletoe lectin B-chain (KML-B) to induce maturation of dendritic cells (DCs). A previous study reported that KML-B induces DC maturation by triggering TLR-4, including expression of costimulatory molecules (CD40, CD80, and CD86), MHC II, and secretion of cytokines in DCs. Additionally, matured DCs by KML-B induced T helper (Th) cell activation and differentiation toward Th1 cells. However, the interaction of KML-B-treated DCs with CD8+ T cells is still poorly understood. In this study, we confirmed the ability of matured DCs by KML-B to stimulate cytotoxic T cells using OT-1 mouse-derived CD8+ T cells. KML-B induced MHC I expression in DCs, stimulation of CD8+ T cell activation and proliferation, and IFN-γ secretion. Moreover, tumor sizes were reduced by KML-B treatment during vaccination of OVA257−264-pulsed DCs. Here, we confirmed induction of CD8+ T cell activation and the antitumor effect of KML-B treatment in DCs.

Although astaxanthin has a variety of biological activities such as anti-oxidant effects, inhibitory effects on skin deterioration and anti-inflammatory effects, its effect on asthma has not been studied. In this paper, the inhibitory effect of astaxanthin on airway inflammation in a mouse model of ovalbumin (OVA)-induced asthma was investigated. We evaluated the number of total cells, Th1/2 mediated inflammatory cytokines in bronchoalveolar lavage fluid (BALF) and airway hyperresponsiveness as well as histological structure. The level of total IgE, IgG1, IgG2a, OVA-specific IgG1, and OVA-specific IgG2a were also examined. The oral administration of 50 mg/mL astaxanthin inhibited the respiratory system resistance, elastance, newtonian resistance, tissue damping, and tissue elastance. Also, astaxanthin suppressed the total cell number, IL-4, and IL-5, and increased the IFN-γ in the BALF. In the sera, total IgE, IgG1, and OVA-specific IgG1 were reduced by astaxanthin exposure and IgG2a and OVA-specific IgG2a were enhanced via oral administration of astaxanthin. Infiltration of inflammatory cells in the lung, production of mucus, lung fibrosis, and expression of caspase-1 or caspase-3 were suppressed in OVA-induced asthmatic animal treated with astaxanthin. These results suggest that astaxanthin may have therapeutic potential for treating asthma via inhibiting Th2-mediated cytokine and enhancing Th1-mediated cytokine.

Lichens are symbiotic organisms which produce distinct secondary metabolic products. In the present study, we tested the cytotoxic activity of 17 lichen species against several human cancer cells and further investigated the molecular mechanisms underlying their anti-cancer activity. We found that among 17 lichens species, F. cucullata exhibited the most potent cytotoxicity in several human cancer cells. High performance liquid chromatography analysis revealed that the acetone extract of F. cucullata contains usnic acid, salazinic acid, Squamatic acid, Baeomycesic acid, d-protolichesterinic acid, and lichesterinic acid as subcomponents. MTT assay showed that cancer cell lines were more vulnerable to the cytotoxic effects of the extract than non-cancer cell lines. Furthermore, among the identified subcomponents, usnic acid treatment had a similar cytotoxic effect on cancer cell lines but with lower potency than the extract. At a lethal dose, treatment with the extract or with usnic acid greatly increased the apoptotic cell population and specifically activated the apoptotic signaling pathway; however, using sub-lethal doses, extract and usnic acid treatment decreased cancer cell motility and inhibited in vitro and in vivo tumorigenic potentials. In these cells, we observed significantly reduced levels of epithelial-mesenchymal transition (EMT) markers and phosphor-Akt, while phosphor-c-Jun and phosphor-ERK1/2 levels were only marginally affected. Overall, the anti-cancer activity of the extract is more potent than that of usnic acid alone. Taken together, F. cucullata and its subcomponent, usnic acid together with additional component, exert anti-cancer effects on human cancer cells through the induction of apoptosis and the inhibition of EMT.

HemoHIM, an herbal preparation of three edible herbs (Angelica gigas Nakai, Cnidium officinale Makino, Paeonia japonica Miyabe) is known to increase the Th1 immune response as well as reduce the allergic response in human mast cells. Here, our goal was to determine whether or not HemoHIM could induce Th1 cell differentiation as well as inhibit the development of airway inflammation. To study Th1/Th2 cell differentiation, naive CD4(+) T cells isolated from C57BL/6 mouse spleens were cultured with or without HemoHIM. To examine airway inflammation, C57BL/6 mice were fed HemoHIM for 4 weeks before sensitization and provocation with ovalbumin (OVA). In an in vitro experiment, naive CD4(+) T cells displayed increased Th1 (IFN-γ(+) cell) as well as decreased Th2 (IL-4(+) cell) differentiation in a HemoHIM concentration-dependent manner. Furthermore, in an airway inflammation mice model, eosinophil numbers in BALF, serum levels of OVA-specific IgE and IgG1, and cytokine (IL-4, IL-5, and IL-13) levels in BALF and the supernatant of splenocytes all decreased upon HemoHIM (100 mg/kg body weight) pretreatment (4 weeks). These results show that HemoHIM attenuated allergic airway inflammation in the mouse model through regulation of the Th1/Th2 balance.