Insulin and IGF-1 extend the lifespan of Caenorhabditis elegans by inhibiting insulin/insulin-like signaling and mTOR signaling pathways: C. elegans - Focused cancer research.

The mutations in Caenorhabditis elegans (C. elegans) that extend lifespan slow down aging by interfering with several signaling pathways, including the insulin/IGF-1 signaling (IIS) pathway, AMP-activated protein kinase (AMPK), and mechanistic target of rapamycin (mTOR). The tumor suppressor pRb (retinoblastoma protein) is believed to be involved in almost all human cancers. Lin-35, the C. elegans orthologue of the tumor suppressor pRb, was included in the study to explore the effects of insulin and IGF-1 because it has been linked to cancer-related pRb function in mammals and exhibits a tumor suppressor effect by inhibiting mTOR or IIS signaling. According to our results, IGF-1 or insulin increased the lifespan of lin-35 worms compared to N2 worms by increasing fertilization efficiency, also causing a significant increase in body size. It was concluded that the expression of daf-2 and rsks-1 decreased after insulin or IGF-1 administration, thus extending the lifespan of C. elegans lin-35 worms through both IIS and mTOR-dependent mechanisms. This suggests that it was mediated by the combined effect of the TOR and IIS pathways. These results, especially obtained in cancer-associated mutant lin-35 worms, will be useful in elucidating the C. elegans cancer model in the future.

Visualization of scientific production in Caenorhabditis elegans: a bibliometric analysis (1980-2023).

Caenorhabditis elegans (C. elegans) is a nematode and model organism whose entire genome has been mapped, which allows for easy observation of the organism's development due to its transparent structure, and which is appealing due to its ease of crossover, ease of culture, and low cost. Despite being separated by nearly a billion years of evolution, C. elegans homologs have been identified for the vast majority of human genes and are associated with C. elegans for many biological processes such as apoptosis, cell signaling, cell cycle, cell polarity, metabolism, and aging. A detailed bibliometric study is performed here to examine publication trends in this field. Data were taken from the Web of Science database and analyzed using the bibliometric application Biblioshiny (RStudio). In terms of publication, the results indicated a gradual increase each year between 1980 and 2023. A total of 20,322 records were issued in 96 countries, the majority of which were in the USA, China, and Japan. The most prolific writers, the journals most engaged in the area, the nations, institutions, and keywords used by authors were all determined using the Web of Science database and bibliometric rules. The number of papers in the C. elegans research field is increasing exponentially, and Genetics is the journal with the highest number of articles. This study presents how research patterns have evolved throughout time. As a result, worldwide cooperation and a potential field can be developed.

Evaluation and normalization of a set of reliable reference genes for quantitative sgk-1 gene expression analysis in Caenorhabditis elegans-focused cancer research.

Multiple signaling pathways have been discovered to play a role in aging and longevity, including the insulin/IGF-1 signaling system, AMPK pathway, TOR signaling, JNK pathway, and germline signaling. Mammalian serum and glucocorticoid-inducible kinase 1 (sgk-1), which has been associated with various disorders including hypertension, obesity, and tumor growth, limits survival in C. elegans by reducing DAF-16/FoxO activity while suppressing FoxO3 activity in human cell culture. C. elegans provides significant protection for a number of genes associated with human cancer. The best known of these are the lin-35/pRb (mammalian ortholog pRb) and CEP-1 (mammalian ortholog p53) genes. Therefore, in this study, we aimed to investigate the expression analyzes of sgk-1, which is overexpressed in many types of mammalian cancer, in mutant lin-35 and to demonstrate the validation of reference genes in wild-type N2 and mutant lin-35 for C. elegans-focused cancer research. To develop functional genomic studies in C. elegans, we evaluated the expression stability of five candidate reference genes (act-1, ama-1, cdc-42, pmp-3, iscu-1) by quantitative real-time PCR using five algorithms (geNorm, NormFinder, Delta Ct method, BestKeeper, RefFinder) in N2 and lin-35 worms. According to our findings, act-1 and cdc-42 were effective in accurately normalizing the levels of gene expression in N2 and lin-35. act-1 and cdc-42 also displayed the most consistent expression patterns, therefore they were utilized to standardize expression level of sgk-1. Furthermore, our results clearly showed that sgk-1 was upregulated in lin-35 worms compared to N2 worms. Our results highlight the importance of definitive validation using mostly expressed reference genes.

A comprehensive and current review on the role of flavonoids in lung cancer-Experimental and theoretical approaches.

BACKGROUND: It is well-known that flavonoids, which can be easily obtained from many fruits and vegetables are widely preferred in the treatment of some important diseases. Some researchers noted that these chemical compounds exhibit high inhibition effect against various cancer types. Many experimental studies proving this ability of the flavonoids with high antioxidant activity are available in the literature. PUROPOSE: The main aim of this review is to summarize comprehensively anticancer properties of flavonoids against the lung cancer in the light of experimental studies and well-known theory and electronic structure principles. In this review article, more detailed and current information about the using of flavonoids in the treatment of lung cancer is presented considering theoretical and experimental approaches. STUDY DESIGN: In addition to experimental studies including the anticancer effects of flavonoids, we emphasized the requirement of the well-known electronic structure principle in the development of anticancer drugs. For this aim, Conceptual Density Functional Theory should be considered as a powerful tool. Searching the databases including ScienceDirect, PubMed and Web of Science, the suitable reference papers for this project were selected. METHODS: Theoretical tools like DFT and Molecular Docking provides important clues about anticancer behavior and drug properties of molecular systems. Conceptual Density Functional Theory and CDFT based electronic structure principles and rules like Hard and Soft Acid-Base Principle (HSAB), Maximum Hardness Principle, Minimum Polarizability, Minimum Electrophilicity Principles and Maximum Composite Hardness Rule introduced by one of the authors of this review are so useful to predict the mechanisms and powers of chemical systems. Especially, it cannot be ignored the success of HSAB Principle in the explanations and highlighting of biochemical interactions. RESULTS: Both theoretical analysis and experimental studies confirmed that flavonoids have higher inhibition effect against lung cancer. In addition to many superior properties like anticancer activity, antimicrobial activity, antioxidant activity, antidiabetic effect of flavonoids, their toxicities are also explained with the help of published popular papers. Action modes of the mentioned compounds are given in detail. CONCLUSION: The review includes detailed information about the mentioned electronic structure principles and rules and their applications in the cancer research. In addition, the epidemiology and types of lung cancer anticancer activity of flavonoids in lung cancer are explained in details.

Modifying Effects of Glucose and Insulin/Insulin-Like Growth Factors on Colon Cancer Cells.

There are only a few experimental studies which have investigated effects of glucose alone, and glucose in combination with insulin/insulin-like growth factors (IGF) on the growth of colon cancer. In the present study, we studied in vitro in human colorectal cancer cells originating from four Dukes' stages of colorectal cancer the effects of glucose, insulin and IGFs on proliferation, migration, cell cycle progression and gene expression of the IGF system. Growth of colon cancer cells originating from a Dukes' stage A was glucose-dependent, whereas growth of cancer cells from Dukes' stage B, C and D was glucose-independent. Stimulatory effects of insulin and IGFs on cell growth were observed only in colon cancer cells originating from Dukes' stage C and D. IGF-II stimulated migration in Dukes' stage B cells only. The growth stimulatory effects in Dukes' stage C and D colorectal cancer cells were accompanied by G2/M arrest and associated with an increased IGF-IR/IGF-II receptor ratio. In conclusion, our in vitro data suggest that the stimulating effects of glucose, IGFs and insulin on proliferation differ between colorectal cancer cells from early and late Dukes' stages. Stimulatory effects of glucose on proliferation appear predominantly present in stage Dukes' stage A colorectal cancer cells, while in contrast growth factor-mediated stimulation of cell proliferation is more pronounced in Dukes' late stage (metastasized) colorectal cancer cells. Moreover, our study suggests that a stringent glucose control may be important to control tumor growth in early stages of colorectal cancer, while inhibition of the endocrine actions of the IGFs and insulin become more important in the late (metastasized) stages of colorectal cancer to restrain growth of colon cancer cells.

In vitro amoebicidal activity of Origanum syriacum and Origanum laevigatum on Acanthamoeba castellanii cysts and trophozoites.

In some patients, complete treatment of amoebic keratitis is difficult because of the resistance of cysts to therapeutic agents. The aim of this study was to evaluate the in vitro amoebicidal activity of methanolic extracts of Origanum syriacum and Origanum laevigatum. In the presence of methanolic extracts (ranging from 1.0 to 32.0mg/ml), numbers of the viable Acanthamoeba castellanii trophozoites and cysts were decreased. Both extracts showed a time and dose dependent amoebicidal action on the trophozoites and cysts. Of the extracts tested, O. syriacum showed the stronger amoebicidal effect on the trophozoites and cysts. In the presence of 32 mg/ml extract, no viable trophozoites were observed within third hour. The extract was also found effective against the cysts within 24th hour. In the case of O. laevigatum, no viable trophozoites were observed within 72nd hour at the concentrations of 16 and 32 mg/ml. As expected, cysts were found more resistant to the extracts than the trophozoites.

Screening of the in vitro amoebicidal activities of Pastinaca armenea (Fisch. & C.A.Mey.) and Inula oculus-christi (L.) on Acanthamoeba castellanii cysts and trophozoites.

The aim of this study is to evaluate the in vitro amoebicidal activity of the aqueous extracts of Pastinaca armenea and Inula oculus-christi from Turkey. In the presence of aqueous extracts (ranging from 1.0 to 32.0 mg/ml), numbers of the viable Acanthamoeba castellanii trophozoites and cysts were decreased during the experimental process. Both extracts showed a time- and dose-dependent amoebicidal action on the trophozoites and cysts. Among the extracts tested, I. oculus showed the strongest amoebicidal effect on the trophozoites and cysts. In the presence of 32.00 mg/ml extract solution in the media, no viable trophozoites were determined from the time of 24 h. Moreover, in the presence of 16.00 mg/ml I. oculus-christi extract, no viable trophozoites were detected in 72 h of the experiment. Effectiveness of I. oculus-christi extract was found moderate against the cysts. In the presence of 32.00 mg/ml extract, only 25.3% of the total cysts were killed effectively. In the case of P. armenea, 40.3% and 23.0% of the trophozoites and cysts were killed in the presence of 32.00 mg/ml extract at the end of the experimental process (72 h), respectively.

In vitro amoebicidal activity of four Peucedanum species on Acanthamoeba castellanii cysts and trophozoites.

Amoebic keratitis is difficult to treat without total efficacy in some patients because of cysts, which is less susceptible than trophozoites to the usual treatments. The aim of this study is to evaluate the in vitro amoebicidal activity of the methanolic extracts of Peucedanum caucasicum, Peucedanum palimbioides, Peucedanum chryseum, and Peucedanum longibracteolatum, which are endemic in Turkish flora except P. caucasicum. Extracts were evaluated for their amoebicidal activities using an inverted light microscope. In the presence of methanolic extracts (ranging from 1.0 to 32.0 mg/ml), numbers of the viable Acanthamoeba castellani trophozoites and cysts were determined during the experimental process (72nd hour). All of the extracts showed a time and dose-dependent amoebicidal action on the trophozoites and cysts. Among the extracts tested, P. longibracteolatum showed the strongest amoebicidal effect on the trophozoites and cysts. In the case of 32 mg/ml concentration of extract, no viable trophozoites or cysts were determined between 24th and 72nd hour. Similar results were obtained from the extract at 16.0 mg/ml concentration against trophozoites. At this concentration value, number of viable cysts was determined as 10.6 ± 2.1 in the 24th hour. In the presence of 8.0 mg/ml extract solution, no viable trophozoites were determined in the 48th hour. At the same concentration, 51% of the cysts were killed by the extract in the 72nd hour. As expected, cysts were found more resistant to the extracts than the trophozoites.

In vitro amoebicidal activities of Teucrium polium and T. chamaedrys on Acanthamoeba castellanii trophozoites and cysts.

Amoebic keratitis is difficult to treat without total efficacy in some patients because of cysts, which are less susceptible than trophozoites to the usual treatments. The aim of this study is to evaluate the in vitro amoebicidal activity of the methanolic extracts of Teucrium polium and Teucrium chamaedrys. In the presence of methanolic extracts (ranging from 1.0 to 32.0 mg/ml), numbers of the viable Acanthamoeba castellani trophozoites and cysts were decreased during the experimental process. Both extracts showed time- and dose-dependent amoebicidal action on the trophozoites and cysts. Among the extracts tested, T. chamaedrys showed the strongest amoebicidal effect on the trophozoites. In the presence of 16 mg/ml or above extract concentrations, no viable trophozoites were observed within 48 h. In the case of T. polium, no viable trophozoites were observed within 48 h at 32 mg/ml concentration. As expected, cysts were found more resistant to the extracts than the trophozoites.