Peptide 17, an inhibitor of YAP/TEAD4 pathway, mitigates lung cancer malignancy

Purpose: To investigate whether and how peptide 17 affects lung cancer cells.Methods: Human lung carcinoma cells, LLC and PC-9, were employed to study the therapeutic effect of peptide 17 on lung cancer. After exogenous expression of peptide 17, a co-immunoprecipitation experiment was used to examine the inhibitory effect of peptide 17. CCK8 assay was employed to assess the lung cancer cells’ viability while clone formation assays were used to assess lung cancer cell proliferation. Colony number was also determined. The stimulatory effect of peptide 17 on lung cancer cell apoptosis was assessed by fluorescence-activated cell sorting (FACS).Results: Peptide 17 efficiently disrupted the interaction between YAP and TEAD4 (p < 0.001), and decreased the expression of CTGF and Cyr61. In addition, lung cancer cell viability and proliferation significantly decreased (p < 0.001) in a time- and concentration-dependent manner. On the other hand, the proportion of apoptotic cells was significantly elevated with rising concentration of peptide 17.Conclusion: Exogenous expression of peptide 17 activates Bcl2/Bax/caspase-9 signal and isresponsible for its inhibitory effects on lung cancer cells. Thus, peptide 17 is a promising target drug in lung cancer treatment.Keywords: Lung cancer, Yes-associate protein, Transcriptional enhancer activation domain 4 (TEAD4), Peptide 17, Apoptosi

Tomato LysM Receptor-Like Kinase SlLYK12 Is Involved in Arbuscular Mycorrhizal Symbiosis

Arbuscular mycorrhiza (AM) is a widespread symbiotic relationship between plants and fungi (Glomeromycota), which improves the supply of water and nutrients to host plants. AM symbiosis is set in motion by fungal chitooligosaccharides and lipochitooligosaccharides, which are perceived by plant-specific LysM-type receptor kinases (LYK). In rice this involves OsCERK1, a LYK also essential for chitin triggered innate immunity. In contrast in legumes, the CERK1 homologous gene experienced duplication events resulting in subfunctionalization. However, it remains unknown whether this subfunctionalization is legume-specific, or has occurred also in other dicot plant species. We identified four CERK1 homologs in tomato (SlLYK1, SlLYK11, SlLYK12, and SlLYK13) and investigated their roles in chitin signaling and AM symbiosis. We found that knockdown of SlLYK12 in tomato significantly reduced AM colonization, whereas chitin-induced responses were unaffected. In contrast, knockdown of SlLYK1 resulted in reduced responses to chitin, but did not alter responses to AM fungi. Moreover, ectopic overexpression of SlLYK1 and SlLYK13 in Nicotiana benthamiana induced cell death, whereas SlLYK12 overexpression did not. Based on our results and comparison with rice OsCERK1, we hypothesize that OsCERK1 orthologs in tomato underwent gene duplication, leading to the subfunctionalization of immunity and symbiosis

Identification of orange color-related gene, PhcpcC, in Pyropia haitanensis

Pigmentation-related mutations can be utilized to distinguish between differentially colored sectors of chimeric thalli, thereby facilitating the efficient breeding of economically valuable Pyropia/Porphyra seaweed species. However, the specific trait loci and alleles responsible for Pyropia/Porphyra coloration have yet to be identified, which limits the applicability of coloration mutants for breeding and genetic analyses. In this study, to preserve the genetic integrity of the population, only four-colored thalli were considered when constructing the doubled haploid (DH) Pyropia haitanensis population, which consisted of 480 homozygous offspring lines (representing the largest DH Pyropia/Porphyra population). The offspring lines in the DH population exhibited both wild-type colored and orange sectors, with a segregation ratio of approximately 1:1, indicating that the orange coloration was controlled by a single nuclear gene. Through BSA-seq analysis (99% confidence interval), a candidate region of 0.5 Mb was identified in the P. haitanensis genome. Additionally, a non-synonymous SNP [A/G] was detected at base-pair position 481 in the coding region of PhcpcC, which encodes a phycocyanin-associated rod linker protein. This SNP locus was verified in both DH and natural populations, with the wild-type colored lines having an A base and the orange lines having a G base at this locus. Therefore, PhcpcC may be the gene associated with the orange coloration of P. haitanensis. The molecular marker developed in this study can be employed to exploit pigmentation mutants for breeding and genetic analyses of Pyropia/Porphyra species

Glucagon-like peptide-1 and its class B G protein-coupled receptors: A long march to therapeutic successes

Theglucagon-likepeptide (GLP)-1receptor (GLP-1R) is a class B G protein-coupled receptor (GPCR) that mediates the action of GLP-1, a peptide hormone secretedfromthreemajor tissues inhumans,enteroendocrine L cells in the distal intestine, a cells in the pancreas, and the central nervous system, which exerts important actions useful in the management of type 2 diabetes mellitus and obesity, including glucose homeostasis and regulation of gastric motility and food intake. Peptidic analogs of GLP-1 have been successfully developed with enhanced bioavailability and pharmacological activity. Physiologic and biochemical studies with truncated, chimeric, and mutated peptides and GLP-1R variants, together with ligand-bound crystal structures of the extracellular domain and the first three-dimensional structures of the 7-helical transmembrane domain of class B GPCRs, have provided the basis for a twodomain-binding mechanism of GLP-1 with its cognate receptor. Although efforts in discovering therapeutically viable nonpeptidicGLP-1R agonists have been hampered, small-moleculemodulators offer complementary chemical tools to peptide analogs to investigate ligand-directed biased cellular signaling of GLP-1R. The integrated pharmacological and structural information of different GLP-1 analogs and homologous receptors give new insights into the molecular determinants of GLP-1R ligand selectivity and functional activity, thereby providing novel opportunities in the design and development of more efficacious agents to treat metabolic disorders

Phytohormones Regulate the Development of Arbuscular Mycorrhizal Symbiosis

Most terrestrial plants are able to form a root symbiosis with arbuscular mycorrhizal (AM) fungi for enhancing the assimilation of mineral nutrients. AM fungi are obligate symbionts that depend on host plants as their sole carbon source. Development of an AM association requires a continuous signal exchange between the two symbionts, which triggers coordinated differentiation of both partners, to enable their interaction within the root cells. The control of the AM symbiosis involves a finely-tuned process, and an increasing number of studies have pointed to a pivotal role of several phytohormones, such as strigolactones (SLs), gibberellic acids (GAs), and auxin, in the modulation of AM symbiosis, through the early recognition of events up to the final arbuscular formation. SLs are involved in the presymbiotic growth of the fungus, while auxin is required for both the early steps of fungal growth and the differentiation of arbuscules. GAs modulate arbuscule formation in a dose-dependent manner, via DELLA proteins, a group of GRAS transcription factors that negatively control the GA signaling. Here, we summarize the recent findings on the roles of these plant hormones in AM symbiosis, and also explore the current understanding of how the DELLA proteins act as central regulators to coordinate plant hormone signaling, to regulate the AM symbiosis

Association between NLPR1, NLPR3, and P2X7R Gene Polymorphisms with Partial Seizures

Objectives. Clinical and experimental evidence has clarified that the inflammatory processes within the brain play a pivotal role in the pathophysiology of seizures and epilepsy. Inflammasomes and P2X7 purinergic receptor (P2X7R) are important mediators during the inflammatory process. Therefore, we investigated the possible association between partial seizures and inflammasomes NLPR1, NLRP3, and P2X7R gene polymorphisms in the present study. Method. A total of 163 patients and 201 health controls were enrolled in this study and polymorphisms of NLPR1, NLRP3, and P2X7R genes were detected using polymerase chain reaction- (PCR-) ligase detection reaction method. Result. The frequency of rs878329 (G>C) genotype with C (CG + CC) was significantly lower among patients with partial seizures relative to controls (OR = 2.033, 95% CI = 1.290–3.204, p=0.002 for GC + CC versus GG). Intriguingly, we found that the significant difference of rs878329 (G>C) genotype and allele frequency only existed among males (OR = 2.542, 95% CI = 1.344–4.810, p=0.004 for GC + CC versus GG), while there was no statistically significant difference among females. However, no significant results were presented for the genotype distributions of rs8079034, rs4612666, rs10754558, rs2027432, rs3751143, and rs208294 polymorphisms between patients and controls. Conclusion. Our study demonstrated the potentially significant role of NLRP1 rs878329 (G>C) in developing susceptibility to the partial seizures in a Chinese Han population

Overexpression of DAPK1 and Beclin1 under oxygen and glucose deprivation conditions promotes excessive autophagy and apoptosis in A549 cells

Abstract In this study, we aimed to determine the specific roles of death‐associated protein kinase 1 (DAPK1) and Beclin1 in non‐small cell lung cancer (NSCLC) under oxygen and glucose deprivation (OGD). We found that OGD caused most cells to shrink, aggregate, and produce many vacuoles in the cytoplasm. Transmission electron microscopy revealed the presence of autophagic vesicles in the OGD group but not in the Control group. Moreover, the cell counting kit‐8 assay showed that cell proliferation was reduced in the OGD group. Quantitative reverse transcription‐polymerase chain reaction, western blot, and cell function assays showed that DAPK1 overexpression under OGD promoted apoptosis and autophagy in A549 cells. The coimmunoprecipitation assay confirmed the interaction between DAPK1 and Beclin1 protein. Moreover, knockdown of Beclin1 inhibited autophagy, but its overexpression promoted apoptosis in A549 cells. In vivo tumorigenesis experiment revealed that overexpression of DAPK1 promoted A549 cell apoptosis. Collectively, overexpression of DAPK1 and Beclin1 under OGD promoted excessive autophagy and apoptosis in A549 cells. Our study may provide a novel therapeutic target and theoretical basis for NSCLC treatment