Applied Biological Chemistry最新文献

Phytophthora infestans (P. infestans) is a highly destructive oomycete that causes the late blight in Solanaceous crops, such as potatoes and tomatoes, reducing crop yield. Although many pesticides are used to control P. infestans, the pathogen has evolved resistance to these chemical pesticides over time. In this study, we employed RNAi technology as an alternative strategy to suppress P. infestans infection. We designed and synthesized two dsRNAs targeting 5' and 3' regions of the Avirulence Protein 3a (Avr3a) gene, a key effector essential for the virulence of P. infestans. Interestingly, the dsRNA targeting the 5' region which contains the conserved RxLR-EER motif of Avr3a exhibited more substantial suppression of P. infestans infection and Avr3a expression level compared to the 3' region targeting dsRNA. Additionally, we identified changes in the expression of genes related to pattern-triggered immunity (PTI) and effector-triggered immunity (ETI) in plants treated with these dsRNAs. In leaves treated with dsRNAs targeting Avr3a, the expression of PTI-related genes was restored, while ETI-related genes showed lower expression levels compared to the mock-treated leaves. These results suggest that dsRNAs targeting Avr3a effectively suppress P. infestans infection, enabling plants to achieve balanced immunity and enhanced defense.

Photoaging damages the skin layers. The tumor necrosis factor-alpha (TNF-α) plays a crucial role in the central mechanism of photoaging. TNF-α production leads to direct damage to skin cells and facilitates the degradation of vital extracellular matrix (ECM) proteins. TNF-α stimulates matrix metalloproteinase-1 (MMP-1) activation This accelerates the loss of skin elasticity and wrinkle formation. Thus, preventing photoaging and delaying the skin aging process are important research objectives, and the development of new anti-aging substances that target the TNF-α and MMP-1 pathways is promising. In this context, the efficacies of four extracts derived from two types of Cephalotaxus harringtonia (CH) buds (CH-10Y-buds, CH-200Y-buds) and leaves (CH-10Y-leaves, CH-200Y-leaves) were investigated, exhibiting a significant reduction in reactive oxygen species (ROS). Among the four extracts, CH-10Y-buds was the most effective in reducing ROS and exhibited the highest amounts of harringtonine and homoharringtonine. The activities of harringtonine, homoharringtonine, and ginkgetin were evaluated; harringtonine exhibited a high efficacy in inhibiting TNF-α-induced inflammatory responses and MMP-1 activation, thereby reducing collagen degradation. These findings suggest that CH-10Y-buds and their components herringtonin are promising candidates for preventing damage caused by photoaging. Our results can facilitate the development of new methods for maintaining skin health and inhibiting the skin aging process. Further research is necessary to comprehensively evaluate the potential efficacy of these candidate substances and investigate their applicability to actual skin. Such studies will aid in the development of more effective anti-aging strategies in the future.

Gene alterations in receptor tyrosine kinases can result in oncogenic driver mutation in non-small cell lung cancer (NSCLC) including in genes like EGFR, ALK and MET. MET amplifications and MET exon14 skipping are the primary genetic changes in MET-altered cancers. Acquired MET mutations mediate resistance to clinical MET-targeted therapy in NSCLC. MET kinase domain secondary mutations (D1228X, Y1230X) confer resistance to type I MET tyrosine kinase inhibitors (TKIs) in METexon14-altered or MET amplified NSCLC. Here, we investigated the preclinical activity of a novel MET inhibitor, CB469, with cell growth, signaling pathway and colony formation. We confirmed that CB469 inhibited the activity of MET wild and secondary mutant kinases, D1228N and Y1230H, as a type II inhibitor. CB469 also inhibited cell growth and cell signaling proteins in MET-activated or MET exon14 skipping-mutated cancer cell lines and NIH/3T3 cells expressing an engineered MET mutant. CB469 exhibited the inhibitory efficacy comparable with that of capmatinib in migration of EBC-1(METwt) and Hs746T(METΔex14) cells. Finally, CB469 showed selective and potent inhibition in MET-activated cancer cells among MET TKIs leading to enhanced selectivity for MET-mutant versus wild type MET with inhibition of cell growth in NIH/3T3 cells expressing an engineered MET mutant variant.

In order to improve the bioavailability of baicalin, this article prepared for α-zein loaded with baicalin composites (α-zein@BA) by pH driven method and they were characterized using scanning electron microscopy, infrared spectroscopy, and measurement of particle size distribution in water solution phase techniques. The digestive behavior and antioxidant activity of composites before and after simulating gastrointestinal fluid in vitro were studied as well. At the same time, molecular dynamics simulation techniques were used to reveal the molecular mechanism behind the formation of the composite between the two. The results indicated that the composites of α-zein@BA were observed to be approximately spherical under a scanning electron microscope, and their particle size was mainly distributed in the range of 94.55-145.10 μm in aqueous solution, whose encapsulation efficiency of baicalin was (86.61 ± 0.71) %. Infrared spectroscopy analysis indicated that α-zein and baicalin mainly formed complexes through hydrogen bonding, electrostatic and hydrophobic interactions. The measurement results of baicalin residue in simulated digestion of gastric and intestinal fluids in vitro are as follows: α-zein@BA > Baicalin, while both significantly increased in the gastric digestion stage (P < 0.05) and significantly decreased in the intestinal digestion stage (P < 0.05). Molecular dynamics simulation studies have shown that baicalin has a promoting effect on protein structural stability, and protein 158SER and GLN196 were mainly formed hydrogen bonds with it, while hydrophobic interactions were mainly manifested between non-polar amino acids such as PHE201 and PRO200. This study indicates that α-zein and baicalin can form stable composites, improving the bioavailability of baicalin.

The sebum on human skin is generated for various causes. The composition of the formed sebum increases the proliferation of Cutibacterium acnes (C. acnes) residing on the skin. As C. acnes proliferates, it produces skin irritants that stimulate the sebaceous glands, increasing sebum production. Skin troubles such as acne may occur. The lysate concentrates of Bacillus stratosphericus (B. stratosphericus), first discovered in the stratosphere, confirmed a 66.35% inhibition of Nitric Oxide (NO) production at 0.50 mg/ml concentration in vitro. Additionally, the growth inhibition efficacy of B. stratosphericus lysate concentrate (BSLC) against C. acnes was confirmed, showing a 95.1% inhibition of growth proliferation at a consistency of 0.50 mg/ml. Based on the in vitro results, the efficacy of BSLC in degrading and reducing sebum was confirmed by reacting it with artificial sebum to various concentrations. The results showed a concentration-dependent decrease in artificial sebum ccording to the efficacy results confirmed in vitro, a clinical trial was conducted to evaluate the daily sebum reduction efficacy of a serum formulation containing 50 mg/ml of BSLC. After a 4-week application, the test group containing BSLC determined a significant 28.68% reduction in sebum levels, demonstrating the practical implications of the research. In conclusion, BSLC is considered to have sufficient industrial value as a valuable ingredient for the cosmetics industry aimed at sebum improvement.

Trichlorobenzenes (TCBs), comprising the isomers 1,2,3-, 1,2,4-, and 1,3,5-TCB, disrupt metabolic processes by inducing liver enzymes involved in xenobiotic metabolism, suggesting a broad toxicological impact. Specifically, exposure to TCBs is associated with significant organ-specific toxicities, such as increased liver and kidney weights in rodents and cytotoxic effects in mammalian cells, which include DNA damage without metabolic activation. Used extensively in industrial and agricultural sectors, TCBs are prevalent pollutants in various ecosystems, including air, food, surface water, groundwater, sediment, soil, and sewage. This is a concern because of their tendency to accumulate in lipid-containing tissues of animals and humans and potentially serious risks to human health and ecosystems. Information showing the presence of TCBs in food, drinking water, and even human breast milk underscores the need for ongoing assessment of the extent of these contaminants in food to measure the potential exposure to these chemicals. TCBs are extracted from various food sample matrices, and then instrumental analysis is performed, typically gas chromatography (GC) coupled with a variety of detectors. This review discusses the occurrence and risk assessment of TCBs in foods, as well as the toxicology and analytical methods related to TCBs.

Skeletal muscle atrophy occurs in several pathological conditions. Among other reasons, high-dose or long-term administration of glucocorticoids increases circulating glucocorticoid levels and causes muscle atrophy. The purpose of this study was to investigate whether Lithospermum erythrorhizon and Lonicera japonica complex extract (LELJ) has a beneficial effect on dexamethasone (Dexa)-induced muscle atrophy. In Dexa-induced myotube atrophy, treatment with LELJ increased myotube diameter, decreased the expression of muscle atrophy markers, and increased the expression of myosin heavy chain (MHC) isoforms. Supplementation with LELJ improved muscle function and performance in mice with Dexa-induced muscle atrophy as demonstrated by grip strength and running tests. Additionally, it increased skeletal muscle mass, size, and expression of MHC isoforms and protein synthesis-related markers. Furthermore, it reduced the upregulated protein levels of skeletal muscle atrophy markers in Dexa-treated mice. Supplementation with LELJ reversed Dexa-induced translocation of the glucocorticoid receptor and forkhead box O3 from the cytosol to the nucleus in skeletal muscles. LELJ also ameliorated age-related muscle loss by extending lifespan and increasing locomotor capacity in Caenorhabditis elegans. We identified loganin and lithospermic acid as bioactive compounds of LELJ and found that treatment with these agents increased myotube diameter, MHC isoform, and puromycin protein levels, and decreased atrophy markers in Dexa-treated myotubes. The current findings underscore how LELJ can prevent Dexa-induced skeletal muscle atrophy, attributing the effects to loganin and lithospermic acid.

Periodontal disease presents a significant challenge in oral health due to its chronic inflammatory nature and subsequent degradation of tooth-supporting structures. Natural compounds have attracted attention for their potential therapeutic effects in alleviating symptoms of periodontitis (PD). In this study, we investigated the impact of Ganoderma lucidum spore oil (GLSO), a lipid component extracted from broken-walled GLS using the supercritical CO₂ extraction method, on PD pathogenesis in vitro and in vivo. Treatment of human gingival fibroblasts with GLSO resulted in a significant reduction in the expression of inflammatory factors, including matrix metalloproteinase (MMP)-1 and interleukin (IL)-8, upregulated by lipopolysaccharide or IL-1β. Molecular mechanism studies revealed that the observed decrease in inflammatory factor expression may be attributed to the inhibition of phosphorylated c-Jun N-terminal kinase activity by GLSO. Furthermore, intraperitoneal injection of GLSO in a ligature-induced PD mouse model led to a notable reduction in periodontal inflammation and alveolar bone loss, accompanied by decreased levels of MMP-1 and IL-8. These in vivo results support the potential therapeutic efficacy of GLSO in alleviating PD symptoms. Overall, our study provides novel insights into the beneficial effects of GLSO in PD management. Further research is warranted to elucidate the underlying molecular mechanisms and explore the clinical applicability of GLSO as a promising therapeutic agent for PD treatment.