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ALI is a grave medical ailment that manifests as abrupt inflammation of the lungs and diminished oxygen levels. It poses a considerable challenge to the medical fraternity, with elevated rates of morbidity and mortality. Our research endeavors to investigate the potential of hibifolin, a flavonoid glucuronide, imbued with potent antioxidant properties, and its molecular mechanism to combat LPS‐induced ALI in mice. The study utilized ICR mice to create an ALI model induced by LPS. Prior to LPS administration, hibifolin was given at 10, 30, or 50 mg/kg, or dexamethasone was given at 1 mg/kg to assess its preventative impact. Changes in lung tissue, pulmonary edema, and lipid peroxidation were analyzed using H&E stain assay, lung wet/dry ratio assay, and MDA formation assay, respectively. Activity assay kits were used to measure MPO activity and antioxidative enzymes (SOD, CAT, GPx) activity in the lungs. Western blot assay was used to determine the phosphorylation of Nrf‐2 and AMPK2 in the lungs. Hibifolin demonstrated a concentration‐dependent improvement in LPS‐induced histopathologic pulmonary changes. This treatment notably mitigated pulmonary edema, lipid peroxidation, and MPO activity in ALI mice. Additionally, hibifolin successfully restored antioxidative enzyme activity in the lungs of ALI mice. Moreover, hibifolin effectively promoted Nrf‐2 phosphorylation and reinstated AMPK2 phosphorylation in the lungs of ALI mice. The results indicate that hibifolin could effectively alleviate the pathophysiological impact of LPS‐induced ALI. This is likely due to its antioxidative properties, which help to restore antioxidative enzyme activity and activate the AMPK2/Nrf2 pathway. These findings are valuable in terms of enhancing our knowledge of ALI treatment and pave the way for further investigation into hibifolin as a potential therapeutic option for lung injuries. [ABSTRACT FROM AUTHOR]

Cyclizine, an over‐the‐counter and prescription antihistamine, finds widespread application in the prevention and treatment of motion sickness, encompassing symptoms such as nausea, vomiting, dizziness, along with its effectiveness in managing vertigo. However, the overuse or misuse of cyclizine may lead to hallucinations, confusion, tachycardia, and hypertension. The molecular mechanisms underlying cyclizine‐induced cytotoxicity and apoptosis remain unclear. During the 24 h incubation duration, RAW264.7 macrophages were exposed to different concentrations of cyclizine. Cytotoxicity was assessed through the lactate dehydrogenase assay. Flow cytometry employing annexin V‐fluorescein isothiocyanate and propidium iodide was utilized to evaluate apoptosis and necrosis. Caspase activity and mitochondrial dysfunction were evaluated through a fluorogenic substrate assay and JC‐1 dye, respectively. Flow cytometry employing fluorogenic antibodies was utilized to evaluate the release of cytochrome c and expression of death receptor, including tumor necrosis factor‐α receptor and Fas receptor. Western blotting was utilized to evaluate the expression of the Bcl2 and Bad apoptotic regulatory proteins. The findings unveiled from the present study demonstrated that cyclizine exerted a concentration‐dependent effect on RAW264.7 macrophages, leading to the induction of cytotoxicity, apoptosis, and necrosis. This compound further activated the intrinsic apoptotic pathway by inducing mitochondrial dysfunction, Bcl2/Bad exchange expression, cytochrome c liberation, and activation of caspases contained caspase 3, 8, and 9. Moreover, the activation of the extrinsic apoptotic pathway was observed as cyclizine induced the upregulation of death receptors and increased caspase activities. Based on our investigations, it can be inferred that cyclizine prompts cytotoxicity and apoptosis in RAW264.7 macrophages in a concentration‐dependent manner by triggering both the intrinsic and extrinsic apoptotic pathways. [ABSTRACT FROM AUTHOR]

Macrophages play an important role in defending the body against invading pathogens. In the face of pathogens, macrophages become activated and release toxic materials that disrupt the pathogens. Macrophage overactivation can lead to severe illness and inflammation. Wogonin has several therapeutic effects, including anti‐inflammatory, anticancer, antioxidant, and neuroprotective effects. No studies have investigated the cytotoxic effects of wogonin at concentrations of more than 0.1 mM in RAW264.7 cells. In this study, RAW 264.7 cells were treated with wogonin, which, at concentrations of more than 0.1 mM, had cytotoxic and genotoxic effects in the RAW264.7 cells, leading to apoptosis and necrosis. Further, wogonin at concentrations of more than 0.1 mM induced caspase‐3, caspase‐8, and caspase‐9 activation and mitochondrial dysfunction and death receptor expression. These results suggest that wogonin induces apoptosis through upstream intrinsic and extrinsic pathways by exhibiting cytotoxic and genotoxic effects. [ABSTRACT FROM AUTHOR]

Cyclizine exhibits sedation and treatment of nausea, vomiting, and motion sickness due to antihistaminic and antimuscarinic effects. Cyclizine has the potential for abuse due to the hallucinogenic and euphoric effect. The response of overdose and illegal abuse of cyclizine includes confusion, tremors, chest pain, ataxia, seizures, and lead to suicide. Macrophage plays the important role in the innate immunity. However, over activation of macrophages results in pro‐inflammatory responses in peripheral tissues. In the present study, cyclizine was found to enhanced the generation of pro‐inflammatory cytokines, including tumor necrosis factor (TNF)‐α, interleukin (IL)‐1β, and IL‐6. We further found that secretion of nitrogen oxide (NO) induced by cyclizine via expression of inducible nitric oxide synthases (iNOS). Cyclizine exhibited parallel stimulation of phosphorylation of nuclear factor‐κB (NFκB) p65, and its up‐stream factor Akt. These results indicated that the expression of pro‐inflammatory cytokines, pro‐inflammatory mediators, and adhesion molecules would be induced by cyclizine via activation of Akt‐NFκB pathway in macrophages. [ABSTRACT FROM AUTHOR]

Concurrent engineering design is widely used to shorten the time needed to introduce a new product and to enhance the quality of the design of the product. However, designers seldom consider the difficulty of assembling a product’s components and modules in the concurrent development process. In fact, the concept of design for assembly is not new. Planning the execution of assembly operations and selecting the assembly sequence during product development will provide designers with interrelated information of design and manufacture that help reduce manufacturing problems. The designer should realize that a reasonable assembly sequence for a product has a significant effect on the efficiency of the entire assembly process. This research focuses on the enhancement of the contact relation matrix approach to the generation of assembly sequences in a product design procedure. A systematic and efficient assembly sequence assistance procedure is proposed to generate feasible assembly sequences and to find an optimal sequence to assemble the product. Compared to the complexity of other methods, this research proposes a modularized contact-rule reasoning approach to generating assembly sequences. The general approach of this research is to (a) develop a modular method for assembly sequence planning, (b) use matrix operations to facilitate the generation of assembly sequences, and (c) generate the assembly sequence of the designed product by searching for subassembly extraction rules. The assembly sequences are then created in the form of a hierarchical structure. The results will assist designers to consider and reduce some manufacture problems in advance that might occur in the process of generation of the recommended design alternative. [ABSTRACT FROM AUTHOR]

Product design is a creative decision-making process that aims to satisfy human needs by releasing good products that can appropriately meet the preferential requirements of customers. In the development of new products, the designer must identify the preference and attitudes of customers toward certain products, ascertain the factors that make products popular in the market, and devise optimum design plans for those products. Biking has become a popular activity due to its contribution to maintaining health. Bicycle-related clothing is known to play an important role in comfort level and safety. Unfortunately, there is hardly any research or designs that consider customer preferences in the bicycle-related clothing design process. Many manufacturers mainly focus on the improvement of the material properties of clothes instead of clothing design to meet the customer requirements. This study uses conjoint analysis in bicycle-related clothing design to provide designers with an efficient approach to identify customer preferences. The lifestyles of users are examined through a massive amount of collected data used to design an attitude measurement chart/questionnaire. Customer requirements are subsequently categorized through factor analysis, and critical requirement attributes are identified for conjoint analysis. Finally, conjoint analysis is used to obtain the optimal design combination for bicycle-related clothing that adheres to the preferences of customers. [ABSTRACT FROM AUTHOR]

Acute lung injury (ALI) is a difficult condition to manage, especially when it is complicated by bacterial sepsis. Hibifolin, a flavonoid glycoside, has anti-inflammatory properties that make it a potential treatment for ALI. However, more research is needed to determine its effectiveness in LPS-induced ALI. In this study, male ICR mice were treated with hibifolin before LPS-induced ALI. Protein content and neutrophil count in bronchoalveolar lavage (BAL) fluid were measured by BCA assay and Giemsa staining method, respectively. The levels of proinflammatory cytokines and adhesive molecules were detected by ELISA assay. The expression of NFκB p65 phosphorylation, IκB degradation, and Akt phosphorylation was assessed by western blot assay. Hibifolin pre-treatment significantly reduced pulmonary vascular barrier dysfunction and neutrophil infiltration into the BAL fluid in LPS-induced ALI mice. In addition, LPS-induced expression of proinflammatory cytokines (IL-1β, IL-6, TNF-α) and adhesive molecules (ICAM-1, VCAM-1) within the BAL fluid were markedly reduced by hibifolin in LPS-induced ALI mice. More, hibifolin inhibited LPS-induced phosphorylation of NFκB p65, degradation of IκB, and phosphorylation of Akt in lungs with ALI mice. In conclusion, hibifolin shows promise in improving the pathophysiological features and proinflammatory responses of LPS-induced ALI in mice through the NFκB pathway and its upstream factor, Akt phosphorylation., (© 2024 Wiley Periodicals LLC.)