Mechanisms underlying isoliquiritigenin-induced apoptosis and cell cycle arrest via ROS-mediated MAPK/STAT3/NF-κB pathways in human hepatocellular carcinoma cells.

Isoliquiritigenin (ISL), a natural flavonoid isolated from plant licorice, has various pharmacological properties, including anticancer, anti-inflammatory, and antiviral effects. However, the underlying mechanisms and signaling pathways of ISL in human hepatocellular carcinoma (HCC) cells remain unknown. In this study, we evaluated the effects of ISL on the apoptosis of human HCC cells with a focus on reactive oxygen species (ROS) production. Our results showed that ISL exhibited cytotoxic effects on two human liver cancer cells in a dose-dependent manner. ISL significantly induced mitochondrial-related apoptosis and cell cycle arrest at the G2/M phase, which was accompanied by ROS accumulation in HepG2 cells. However, pretreatment with an ROS scavenger, N-acetyl-l-cysteine (NAC), inhibited ISL-induced apoptosis. In addition, ISL increased the phosphorylation levels of c-Jun N-terminal kinase (JNK), p38 kinase and inhibitor of NF-κB (IκB), and decreased the phosphorylation levels of extracellular signal-regulated kinase (ERK), signal transducer and activator of transcription 3 (STAT3), nuclear factor-kappa B (NF-κB), these effects were blocked by NAC and mitogen-activated protein kinase (MAPK) inhibitors. Taken together, the findings of this study indicate that ISL induced HepG2 cell apoptosis via ROS-mediated MAPK, STAT3, and NF-κB signaling pathways. Therefore, ISL may be a potential treatment for human HCC, as well as other cancer types.

The compound 2-(naphthalene-2-thio)-5,8-dimethoxy-1,4-naphthoquinone induces apoptosis via reactive oxygen species-regulated mitogen-activated protein kinase, protein kinase B, and signal transducer and activator of transcription 3 signaling in human gastric cancer cells.

Hit, Lead & Candidate Discovery It is reported that 1,4-naphthoquinones and their derivatives have potent antitumor activity in various cancers, although their clinical application is limited by observed side effects. To improve the therapeutic efficacy of naphthoquinones in the treatment of cancer and to reduce side effects, we synthesized a novel naphthoquinone derivative, 2-(naphthalene-2-thio)-5,8-dimethoxy-1,4-naphthoquinone (NTDMNQ). In this study, we explored the effects of NTDMNQ on apoptosis in gastric cancer cells with a focus on reactive oxygen species (ROS) production. Our results demonstrated that NTDMNQ exhibited the cytotoxic effects on gastric cancer cells in a dose-dependent manner. NTDMNQ significantly induced mitochondrial-related apoptosis in AGS cells and increased the accumulation of ROS. However, pre-treatment with N-acetyl-L-cysteine (NAC), an ROS scavenger, inhibited the NTDMNQ-induced apoptosis. In addition, NTDMNQ increased the phosphorylation of p38 kinase and c-Jun N-terminal kinase (JNK) and decreased the phosphorylation of extracellular signal-regulated kinase (ERK), protein kinase B (Akt), and Signal Transducer and Activator of Transcription 3 (STAT3); these effects were blocked by mitogen-activated protein kinase (MAPK) inhibitor and NAC. Taken together, the present findings indicate that NTDMNQ-induced gastric cancer cell apoptosis via ROS-mediated regulation of the MAPK, Akt, and STAT3 signaling pathways. Therefore, NTDMNQ may be a potential treatment for gastric cancer as well as other tumor types.

Bamboo invasion alters Collembola community composition varying with life-forms.

BACKGROUND: Plant invasions are a global concern. In eastern China, bamboo is rapidly expanding, negatively influencing neighbouring forest communities. However, studies on how bamboo invasion affects belowground communities, especially for soil invertebrates, are still lacking. In the present study, we focused on a highly abundant and diverse fauna taxon - Collembola. Collembola communities have three typical life-forms (i.e., epedaphic, hemiedaphic, and euedaphic) inhabiting different soil layers and playing distinct roles in ecological processes. Specifically, we studied their abundance, diversity, and community composition at the three stages of bamboo invasion: uninvaded secondary broadleaf forest, moderately invaded mixed bamboo forest, and completely invaded bamboo (Phyllostachys edulis) forest. RESULTS: Our results showed that bamboo invasion negatively influenced Collembola communities by decreasing their abundance and diversity. Moreover, Collembola life-forms differed in their responses to bamboo invasion, with surface-dwelling Collembola being more vulnerable to bamboo invasion than soil-living Collembola. CONCLUSION: Our findings indicate differential response patterns to bamboo invasion within Collembola communities. The negative effects of bamboo invasion on soil surface-dwelling Collembola may further influence ecosystem functioning. © 2023 Society of Chemical Industry.

The value of chest computed tomography in evaluating lung cancer in a lobe affected by stable pulmonary tuberculosis in middle-aged and elderly patients: A preliminary study.

Introduction: Lung cancer can be masked by coexisting stable tuberculosis lesions, which may result in delayed lung cancer diagnosis and treatment. Information about pulmonary tuberculosis patients who are at high-risk of developing lung cancer is scarce. We aimed to examine the value of chest computed tomography (CT) in evaluating lung cancer in a lobe affected by stable pulmonary tuberculosis in middle-aged and elderly patients. Methods: In this single-centered, retrospective, observational study, we enrolled 41 middle-aged and elderly patients with pulmonary tuberculosis who developed lung cancer in the same lobe from January 30, 2011 to December 30, 2020. Comparisons of the clinical and chest CT data were made with age-matched and sex-matched control groups of patients with stable pulmonary tuberculosis but no lung cancer diagnosis (n = 38). Results: Seventeen patients in the lung cancer group (41%) were initially misdiagnosed. Compared to lesions in the control group, lesions in the lung cancer group were significantly more likely to demonstrate the following CT features: large size, vessel convergence, lobulation, spiculation, spinous protuberance, bronchial obstruction or stenosis, vacuolation, ground-glass opacification, heterogeneous or homogeneous enhancement, and gradual increase in size. Nodular enlargement showed the best diagnostic performance in the diagnosis of lung cancer in a lobe affected by tuberculosis (area under the receiver operating characteristic curve = 0.974; P <0.001; accuracy = 98.2%; sensitivity =94.7%; specificity = 100%). Conclusion: Chest CT might play an important role in early diagnosis of lung cancer in a lobe affected by tuberculosis. Regular CT re-examination is necessary in continuous controls monitoring of patients with stable pulmonary tuberculosis. The study indicates necessity of prospective study in this field.

Trypoxylus dichotomus Gut Bacteria Provides an Effective System for Bamboo Lignocellulose Degradation.

Fast-growing bamboo may be a source of high-quality cellulose with the potential to contribute to energy sustainability, if an efficient and low-cost solution to bamboo cellulose decomposition can be developed. This study compared the gut microbiomes of rhinoceros beetle (Trypoxylus dichotomus) feeding on bamboo and wood fiber. The results revealed that diet has a distinctive effect on microbial composition in the midgut, including its most abundant microorganisms that in the fermentation and chemoheterotroph pathways. After identifying the 13 efficient bacterial isolates, we constructed a natural bacterial system based on the microbial relative abundance and an artificial bacterial system with equal proportions of each isolate to catabolize bamboo lignocellulose. The isolate Enterobacter sp. AZA_4_5 and the natural system showed higher degradation efficiency than other single strains or the artificial system. The results can thus serve as important reference for further research and development of a synthetic bacterial consortium to maximize lignocellulolytic ability. IMPORTANCE Bamboo produces a great yield of lignocellulosic biomass due to its high efficiency in carbon fixing. The gut microbiome of Trypoxylus dichotomus differed between bamboo and wood fiber diets. The lignocellulosic pathways were enriched in the gut bacteria of the bamboo diet. The highly efficient bacterial isolates were identified from midgut, whereas the natural bacterial system as well as one isolate showed the higher degradation efficiency of bamboo lignocellulose. The results indicate that the gut bacteria could provide an effective system to utilize the bamboo lignocellulosic biomass.

The clinical significance of microRNA-409 in pancreatic carcinoma and associated tumor cellular functions.

In recent years, the increasing incidence of pancreatic carcinoma (PC) patients has become one of the hot issues in the world. microRNAs (miRNAs) can act as oncogenes or tumor suppressor genes and have unpredictable effects on tumors, thus affecting the prognosis and survival of cancer patients. In this paper, we mainly studied the role of microRNA (miR)-409 in PC. The expression levels of miR-409 were analyzed by qRT-PCR. Kaplan-Meier curve and Cox regression were used to analyze the relationship between miR-409 and patient prognosis. The effects of miR-409 on the abilities of proliferation, migration and invasion were detected by CCK-8 and Transwell. The expression levels of miR-409 were down-regulated in PC, compared with normal controls. The prognosis of patients with low miR-409 expression is significantly poor in comparison with those with high expression. The down-regulation of miR-409 was conducive to the proliferation, migration and invasion of PC cells. miR-409 is a tumor suppressor of PC, the clinical significance of miR-409 in pancreatic cancer and related tumor cell function was clarified.

The effect of sorghum resistance resistant starch-mediated equol on the histological morphology of the uterus and ovaries of postmenopausal rats.

Equol is a metabolite of daidzein and has a higher biological activity than daidzein. Equol, combined with estrogen receptors, can reduce the incidence of diseases such as cardiovascular disease, osteoporosis, and breast cancer; more effectively alleviate the symptoms of perimenopausal syndrome; and improve age-related decline of the uterus and ovaries. Research has shown that food composition can greatly affect the formation of equol in the intestinal tract. In the intestines, the content of nonstarch polysaccharides that can stimulate fermentation is high, thereby allowing intestinal bacteria to quickly and completely transform the daidzein into equol. This study used Sprague Dawley (SD) rats as a model, where menopause was established through direct intragastric administration of formistan. In the 6-week-long experiment, intragastric administration of RS while feeding bean pulp reduced the body weight of postmenopausal rats, reduced the efficiency of feed utilization of rats, and increased the weight of organs such as the uterus and ovaries. Routine blood indexes showed that no adverse reactions were produced by intragastric administration of RS. 16s rDNA sequencing further verified Lactobacillus and Clostridium XIVa, as the bacteria that converted daidzein into equol.

The resistant starch from sorghum regulates lipid metabolism in menopausal rats via equol.

Equol is a metabolite of daidzein and has a higher biological activity than daidzein. High levels of non-starch polysaccharides can stimulate fermentation in the intestine leading to rapid conversion of daidzein into equol that has great potential to reduce obesity in postmenopausal women. In the present study, female Sprague-Dawley rats were used to establish a menopausal model by oral administration of formestane and to compare the protective effect of resistant starch on lipid metabolism, with or without soybean feed. The resistant starch was found to effectively control body weight and adipose tissue quality, while increasing the high-density lipoprotein cholesterol (HDL-C) concentration and lowering the glycerol, triacylglycerols (TG), total cholesterol (TC), and low density lipoprotein cholesterol (LDL-C) concentrations with soybean feed. Equol inhibited the expression of SREBPC1 gene by inhibiting SHP in the liver via transcription factor FXR, thereby inhibiting the synthesis of triglyceride and fatty acid in the liver. PRACTICAL APPLICATIONS: Intake of a certain amount of resistant starch while eating the soy product can better regulate lipid metabolism in menopausal obese rats compared to consumption of resistant starch alone. Studies have shown that resistant starch converts daidzein to Equol by regulating the structure of the intestinal flora and acts as an estrogen in menopausal rats. This research will further expand the health applications of resistant starch and provide useful information for the food industry.

Liquiritin inhibits proliferation and induces apoptosis in HepG2 hepatocellular carcinoma cells via the ROS-mediated MAPK/AKT/NF-κB signaling pathway.

Liquiritin (LIQ), a major constituent of Glycyrrhiza Radix, exhibits various pharmacological activities. In this study, to explore the potential anti-cancer effects and its underlying molecular mechanisms of LIQ in hepatocellular carcinoma (HCC) cells. LIQ significantly decreased viability and induced apoptosis in HepG2 cells by decreasing mitochondrial membrane potential and regulating Bcl-2 family proteins, cytochrome c, cle-caspase-3, and cle-PARP. The cell cycle analysis and western blot analysis revealed that LIQ induced G2/M phase arrest through increased expression of p21 and decreased levels of p27, cyclin B, and CDK1/2. The flow cytometry and western blot analysis also suggested that LIQ promoted the accumulation of ROS in HepG2 cells and up-regulated the phosphorylation expression levels of p38 kinase, c-Jun N-terminal kinase (JNK), and inhibitor of NF-κB (IκB-α); the phosphorylation levels of extracellular signal-regulated kinase (ERK), protein kinase B (AKT), signal transducer activator of transcription 3 (STAT3), and nuclear factor kappa B (NF-κB) were down-regulated. However, these effects were reversed by N-acetyl-L-cysteine (NAC), MAPK, and AKT inhibitors. The findings demonstrated that LIQ induced cell cycle arrest and apoptosis via the ROS-mediated MAPK/AKT/NF-κB signaling pathway in HepG2 cells, and the LIQ may serve as a potential therapeutic agent for the treatment of human HCC.

Cytisine exerts anti-tumour effects on lung cancer cells by modulating reactive oxygen species-mediated signalling pathways.

Cytisine is a natural product isolated from plants and is a member of the quinolizidine alkaloid family. This study aims to investigate the effect of cytisine in human lung cancer. Cell viability was determined using the CCK-8 assay, and the results showed that cytisine inhibited the growth of lung cancer cell lines. The apoptotic effects were evaluated using flow cytometry, and the results showed that cytisine induced mitochondrial-dependent apoptosis through loss of the mitochondrial membrane potential; increased expression of BAD, cleaved caspase-3, and cleaved-PARP; and decreased expression levels of Bcl-2, pro-caspase-3, and pro-PARP. In addition, cytisine caused G2/M phase cell cycle arrest that was associated with inhibiting the AKT signalling pathway. During apoptosis, cytisine increased the phosphorylation levels of JNK, p38, and I-κB, and decreased the phosphorylation levels of ERK, STAT3, and NF-κB. Furthermore, cytisine treatment led to the generation of ROS, and the NAC attenuated cytisine-induced apoptosis. In vivo, cytisine administration significantly inhibited the lung cancer cell xenograft tumorigenesis. In conclusion, cytisine plays a critical role in suppressing the carcinogenesis of lung cancer cells through cell cycle arrest and induction of mitochondria-mediated apoptosis, suggesting that it may be a promising candidate for the treatment of human lung cancer.

2-(4-methoxyphenylthio)-5,8-dimethoxy-1,4-naphthoquinone induces apoptosis via ROS-mediated MAPK and STAT3 signaling pathway in human gastric cancer cells.

The 1,4-naphthoquinones and their derivatives have garnered great interest due to their antitumor pharmacological properties in various cancers; however, their clinical application is limited by side effects. In this study, to reduce side effects and improve therapeutic efficacy, a novel 1,4-naphthoquinone derivative-2-(4-methoxyphenylthio)-5,8-dimethoxy-1,4-naphthoquinone (MPTDMNQ) was synthesized. We investigated the effects and underlying mechanisms of MPTDMNQ on cell viability, apoptosis, and reactive oxygen species (ROS) generation in human gastric cancer cells. Our results showed that MPTDMNQ decreased cell viability in nine human gastric cancer cell lines. MPTDMNQ significantly induced apoptosis accompanied by the accumulation of ROS in GC cells. However, pre-treatment with the ROS scavenger N-acetyl-L-cysteine (NAC) attenuated the MPTDMNQ-induced apoptosis. Moreover, MPTDMNQ decreased the phosphorylation levels of extracellular signal-regulated kinase (ERK) and signal transducer and activator of transcription 3 (STAT3); and increased the phosphorylation levels of c-Jun N-terminal kinase (JNK) and p38 kinase. However, phosphorylation was inhibited by NAC and a mitogen-activated protein kinase (MAPK) inhibitor. These findings showed that MPTDMNQ induced AGS cell apoptosis via ROS-mediated MAPK and STAT3 signaling pathways. Thus, MPTDMNQ may be a promising candidate for treating gastric cancer.

Cryptotanshinone induces reactive oxygen species­mediated apoptosis in human rheumatoid arthritis fibroblast­like synoviocytes.

The present study investigated the mechanisms of apoptosis induced by cryptotanshinone (CT) in human rheumatoid arthritis fibroblast­like synoviocytes (RA­FLSs). Cell Counting kit­8 assay was performed to determine the cytotoxic effects of CT in human RA­FLSs, including primary RA­FLS, HFLS­RA and MH7A cells, and in HFLS cells derived from normal synovial tissue. Annexin V­FITC/PI staining was used to detect the apoptotic effects of CT in HFLS­RA and MH7A cells. Flow cytometry was performed to detect the apoptotic and reactive oxygen species (ROS) levels induced by CT in HFLS­RA cells. Western blotting was used to assess the expression levels of proteins associated with apoptosis and with the mitogen­activated protein kinase (MAPK), protein kinase B (Akt), and signal transducer and activator of transcription­3 (STAT3) signaling pathways. The results demonstrated that CT treatment significantly suppressed HFLS­RA and MH7A cell growth, whereas no clear inhibitory effect was observed in normal HFLS cells. CT exposure downregulated the expression levels of B­cell lymphoma 2 (Bcl­2), p­Akt, p­extracellular signal­related kinase and p­STAT3, while it upregulated the expression levels of Bcl­2­associated death promoter (Bad), caspase­3, poly (ADP­ribose) polymerase (PARP), p­p38 and p­c­Jun N­terminal kinase. Following ROS scavenging, the CT­induced apoptosis and altered expression levels of Bcl­2, Bad, cleaved caspase­3 and cleaved PARP were restored. Furthermore, the Akt, MAPK and STAT3 signaling pathways were regulated by intracellular ROS. These results suggest that ROS­mediated Akt, MAPK and STAT3 signaling pathways serve important roles in the CT­induced apoptosis of RA­FLSs.