Yi-Chich Chiu

Resveratrol inhibits NLRP3 inflammasome activation by preserving mitochondrial integrity and augmenting autophagy

The NLRP3 inflammasome is a caspase‐1‐containing multi‐protein complex that controls the release of IL‐1β and plays important roles in the development of inflammatory disease. Here, we report that resveratrol, a polyphenolic compound naturally produced by plants, inhibits NLRP3 inflammasome‐derived IL‐1β secretion and pyroptosis in macrophages. Resveratrol inhibits the activation step of the NLRP3 inflammasome by suppressing mitochondrial damage. Resveratrol also induces autophagy by activating p38, and macrophages treated with an autophagy inhibitor are resistant to the suppressive effects of resveratrol. In addition, resveratrol administration mitigates glomerular proliferation, glomerular sclerosis, and glomerular inflammation in a mouse model of progressive IgA nephropathy. These findings were associated with decreased renal mononuclear leukocyte infiltration, reduced renal superoxide anion levels, and inhibited renal NLRP3 inflammasome activation. Our data indicate that resveratrol suppresses NLRP3 inflammasome activation by preserving mitochondrial integrity and by augmenting autophagy. J. Cell. Physiol. 230: 1567–1579, 2015.

Bamboo vinegar decreases inflammatory mediator expression and NLRP3 inflammasome activation by inhibiting reactive oxygen species generation and protein kinase C-α/δ activation.

Bamboo vinegar (BV), a natural liquid derived from the condensation produced during bamboo charcoal production, has been used in agriculture and as a food additive, but its application to immune modulation has not been reported. Here, we demonstrated that BV has anti-inflammatory activities both in vitro and in vivo. BV reduced inducible nitric oxide synthase expression and nitric oxide levels in, and interleukin-6 secretion by, lipopolysaccharide-activated macrophages without affecting tumor necrosis factor-α secretion and cyclooxygenase-2 expression. The mechanism for the anti-inflammatory effect of BV involved decreased reactive oxygen species production and protein kinase C-α/δ activation. Furthermore, creosol (2-methoxy-4-methylphenol) was indentified as the major anti-inflammatory compound in BV. Impaired cytokine expression and NLR family, pyrin domain-containing 3 (NLRP3) inflammasome activation was seen in mice treated with creosol. These findings provide insights into how BV regulates inflammation and suggest that it may be a new source for the development of anti-inflammatory agents or a healthy supplement for preventing and ameliorating inflammation- and NLRP3 inflammasome-related diseases, including metabolic syndrome.

Polyenylpyrrole Derivatives Inhibit NLRP3 Inflammasome Activation and Inflammatory Mediator Expression by Reducing Reactive Oxygen Species Production and Mitogen-Activated Protein Kinase Activation

Two polyenylpyrroles from a soil ascomycete Gymnoascus reessii were previously identified as hit compounds in screening for cytotoxicity against lung cancer cells. These compounds and various analogs, which have been previously synthesized and tested for anti-lung cancer cell activity, were tested for anti-inflammatory activity. After preliminary screening for cytotoxicity for RAW 264.7 murine macrophage cells, the non-toxic compounds were tested for anti-inflammatory activity using lipopolysaccharide (LPS)-activated RAW 264.7 cells. Compounds 1h, 1i, and 1n reduced LPS-induced nitric oxide (NO) production, with respective ED50 values of 15 ± 2, 16 ± 2, and 17 ± 2 µM. They also reduced expression of inducible NO synthase and interleukin-6 (IL-6) without affecting cyclooxygenase-2 expression. Compound 1h also reduced secretion of IL-6 and tumor necrosis factor-α by LPS-activated J774A.1 murine macrophage cells, primary mice peritoneal macrophages, and JAWSII murine bone marrow-derived dendritic cells and reduced NLRP3 inflammasome-mediated interleukin-1β (IL-1β) secretion by LPS + adenosine triphosphate-activated J774A.1 and JAWSII cells. The underlying mechanisms for the anti-inflammatory activity of compound 1h were found to be a decrease in LPS-induced reactive oxygen species (ROS) production, mitogen-activated protein kinase phosphorylation, and NF-κB activation and a decrease in ATP-induced ROS production and PKC-α phosphorylation. These results provide promising insights into the anti-inflammatory activity of these conjugated polyenes and a molecular rationale for future therapeutic intervention in inflammation-related diseases. They also show how compound 1h regulates inflammation and suggest it may be a new source for the development of anti-inflammatory agents to ameliorate inflammation- and NLRP3 inflammasome-related diseases.

Peroxyauraptenol Inhibits Inflammation and NLRP3 Inflammasome Activation by Inhibiting Reactive Oxygen Species Generation and Preserving Mitochondrial Integrity.

Peroxyauraptenol (PXT) is a peroxide-containing coumarin compound isolated from the seeds of Cnidium monnieri. PXT exerts anti-inflammatory activities, as it reduces the levels of inducible nitric oxide synthase, nitric oxide, IL-6, and NLRP3 inflammasome-derived IL-1β in lipopolysaccharide-activated macrophages. PXT also exerts anti-inflammatory activity by reducing reactive oxygen species generation (including mitochondrial), mitogen-activated protein kinase, protein kinase C-α/δ phosphorylation, and the release of mitochondrial DNA into the cytosol. In addition, PXT suppresses the phagocytic activity of macrophages and IL-1β secretion by Klebsiella pneumoniae-infected macrophages. The unique peroxide group is important for the anti-inflammatory activity of PXT, as this activity is reduced when the peroxide group is replaced by a hydroxyl group. These findings suggest that PXT may be a candidate for the development of anti-inflammatory agents or a healthy supplement for preventing and ameliorating inflammation-related diseases.

Capsular Polysaccharide Is Involved in NLRP3 Inflammasome Activation by Klebsiella pneumoniae Serotype K1.

ABSTRACT Klebsiella pneumoniae (strain 43816, K2 serotype) induces interleukin-1β (IL-1β) secretion, but neither the bacterial factor triggering the activation of these inflammasome-dependent responses nor whether they are mediated by NLRP3 or NLRC4 is known. In this study, we identified a capsular polysaccharide (K1-CPS) in K. pneumoniae (NTUH-K2044, K1 serotype), isolated from a primary pyogenic liver abscess (PLA K. pneumoniae), as the Klebsiella factor that induces IL-1β secretion in an NLRP3-, ASC-, and caspase-1-dependent manner in macrophages. K1-CPS induced NLRP3 inflammasome activation through reactive oxygen species (ROS) generation, mitogen-activated protein kinase phosphorylation, and NF-κB activation. Inhibition of both the mitochondrial membrane permeability transition and mitochondrial ROS generation inhibited K1-CPS-mediated NLRP3 inflammasome activation. Furthermore, IL-1β secretion in macrophages infected with PLA K. pneumoniae was shown to depend on NLRP3 but also on NLRC4 and TLR4. In macrophages infected with a K1-CPS deficiency mutant, an lipopolysaccharide (LPS) deficiency mutant, or K1-CPS and LPS double mutants, IL-1β secretion levels were lower than those in cells infected with wild-type PLA K. pneumoniae. Our findings indicate that K1-CPS is one of the Klebsiella factors of PLA K. pneumoniae that induce IL-1β secretion through the NLRP3 inflammasome.

Development of a tubing-grafting robotic system for fruit-bearing vegetable seedlings.

This research aims to develop an automatic tubing-grafting robotic system using soft rubber tubes as the grafting material that is suitable for the rootstock and scion of fruit-bearing vegetables having similar stem diameter, such as tomato, bitter melon and sweet pepper. Compared with grafting using grafting clips, the soft rubber tube approach is low-cost and minimizes water loss from the grafting wounds. Moreover, as the grafted seedlings grow, the soft rubber tubes automatically peel off from seedlings due to embrittlement and this saves recycling. The tubing-grafting robotic system is made up of six major units, namely the rootstock gripping, the rootstock cutting, the scion gripping, the scion cutting, the tube supplying, and the guiding units. A pneumatic mechanism with a programmable logic controller is used to process the sequential events needed. In the guiding unit, a pair of guiding sleeves ensures that the rootstock and scion are able to be inserted into the rubber tube smoothly even if the stem of either the rootstock or scion is deflective. The experimental results indicated that the average grafting success rate is over 93.8% and the system has a working capability of 327 seedlings per hour; the overall adhesion rate for the grafted seedlings kept in an acclimatization chamber is over 84.4%. Demonstrations were held and farmers were highly satisfied with the system performance.

Development of a Circular Grafting Robotic System for Watermelon Seedlings

The aim of this research was to develop a top plug-in grafting robotic system that is applicable for grafting a scion into a mature rootstock before the scions cotyledons spread. This would require the scion to be very delicate and greatly different from the rootstock in terms of seedling age. The grafting robotic system for watermelon seedlings consists of a rootstock processing unit and a scion processing unit, with dimensions of 120 cm 105 cm 130 cm. Both the rootstock and scion processing unit have a rotating disc, with the disc of the rootstock processing unit being lower than that of the scion processing unit; furthermore, the two discs rotate in opposite directions. A Geneva Wheel intermittent motion mechanism was adopted to drive the discs so that simultaneous and opposite movement was possible. The rootstock processing unit takes charge of removing the leaf bud from the rootstock seedling and drilling a hole for the scion, while the scion processing unit performs the action of cutting the scion seedling to make a sharp angle and finishes the grafting operation by inserting the scion into the hole in the rootstock. The developed grafting robotic system is characterized by the absence of grafting clips. This research employs bottle gourd Chiang-Li #1 as the rootstock and watermelon Fu-Bao #2 as the scion to conduct a series of mechanical grafting experiments. The experimental results showed that the grafting robotic system was able to accurately finish all grafting procedures and operations, with an average success rate of 95% and a working capability of 480 seedlings per hour. Demonstrations were held and farmers were highly satisfied with the systems functions and its performance.

Study of an Autonomous Fruit Picking Robot System in Greenhouses

Abstract The objective of this research was to develop an autonomous picking robot system for greenhouse-grown tomatoes, which consists of four major components: the end-effector, machine vision, robot carrier, and control system. The graphical programming language LabVIEW ver. 7.1 was employed to develop the image processing and control system. The experimental results showed the success rates of the integrated picking were 94.83 %, 91.83 %, and 89.63 %, respectively. The average picking time needs about 35.96 s/sample, with a throughput of 100.1 samples/h. Consequently, an autonomous picking robot system was successfully developed and it needs to be further tested for real tomato picking operations in greenhouses in the future.

Predicting the production schedule of paddy-rice nursery

The objective of this study was to develop a linear programming model to analyze the production schedule of rice seedlings grown in the nursery. The model can help the managers of rice seedling centers in Taiwan to make better production decisions and maximize profit (all monetary units are expressed in US dollars). To verify the model, a rice seedling center was chosen for analysis of the first rice crop in 1997. The results show that the cost is about

Growth and union acclimation process of sweet pepper grafted by a tubing-grafting robotic system

51,856 yielding a profit of about