BACKGROUND: Inflammatory conditions are involved in the pathophysiology of cancer. Recent findings have revealed that excessive salt and fat intake is involved in the development of severe inflammatory reactions.

METHODS: A literature search was performed on various online databases (PubMed, Scopus, and Google Scholar) regarding the roles of high salt and fat intake in the induction of inflammatory reactions and their roles in the etiopathogenesis of cancer.

RESULTS: The results indicate that high salt and fat intake can induce severe inflammatory conditions. However, various inflammatory conditions have been strongly linked to the development of cancer. Hence, high salt and fat intake might be involved in the pathogenesis of cancer progression via putative mechanisms related to inflammatory reactions.

CONCLUSION: Reducing salt and fat intake may decrease the risk of cancer.

BACKGROUND: Vascular smooth muscle cells (VSMCs) are mature cells that play critical roles in both normal and aberrant cardiovascular conditions. In response to various environmental cues, VSMCs can dedifferentiate from a contractile state to a highly proliferative synthetic state through the so-called ‘phenotypic switching’ process. Changes in VSMC phenotype contribute to numerous vascular-related diseases, including atherosclerosis, calcification, and restenosis following angioplasty. Adventitial VSMC progenitor cells also contribute to formation of the neointima.

METHODS/RESULTS: Herein, we review both, the roles of VSMC differentiation in vascular diseases, and the in vitro models used to investigate the molecular mechanisms involved in the regulation of VSMC differentiation and phenotype modulation.

CONCLUSION: A comprehensive understanding of VSMC behavior in vascular diseases is essential to identify new therapeutic targets for the prevention and treatment of cardiovascular diseases.

BACKGROUND: Multicellular organisms rely on the transmission of information between cells to coordinate various biological processes during growth and development. Plants, like animals, utilize small peptide ligands as signaling molecules to transmit information between cells. These polypeptides typically act as extracellular messengers that are perceived by membrane-bound receptors, which then transduce the signal into the recipient cell to modify downstream gene transcription. The CLAVATA3/EMBRYO SURROUNDING REGION-RELATED (CLE) proteins represent one of the largest and best understood families of small polypeptides in plants. Members of the CLE family play critical roles in mediating cell fate decisions during plant development, particularly within the unique meristem structures that contain stem cell reservoirs acting as sources of cells for continuous organ formation.

OBJECTIVE: Here we review the roles of CLE family members in regulating the activity of the shoot apical meristems that generate the aerial parts of the plants, and of the vascular meristems that produce the sugar- and water-conducting tissues.

METHODS: A systematic literature search was performed using the Google Scholar and PubMed search engines. The keywords “CLE”, “CLV3”, “TDIF”, “meristem”, and “plant stem cells” were used as search terms. The 95 retrieved articles, dating from 1992, were organized by topic and their key findings incorporated into the text.

RESULTS: We summarize our current understanding of how the CLE peptide CLV3 orchestrates the activity of shoot apical meristems, describing its expression, processing and movement, as well as its intracellular signal transduction pathways, key target genes and downstream gene regulatory networks. We also discuss the roles of CLE peptide signaling in the vascular meristems to promote procambial cell proliferation and suppress xylem differentiation.

CONCLUSIONS: Signaling pathways mediated by CLE peptides are critical for stem cell maintenance and differentiation in shoot apical and vascular meristems in plants, exposing CLE genes as potential targets for increasing yield and biomass production. While large numbers of CLE genes are being discovered in plants, only a few have been functionally characterized. We anticipate that future research will continue to elucidate the roles of the CLE family in plant development, and their potential impacts on agriculture and commerce.

BACKGROUND: The development of prostate cancer from a clinically localized, hormone-naive state to a hormone-refractory phenotype involves a complex interplay of protein kinase C (PKC) and activator protein-1 (AP-1). Therefore, the present study aimed to uncover the roles of PKC and AP-1 through midostaurin-mediated regulation—a multi-target protein kinase inhibitor.

METHODS: Androgen Receptor-negative, hormone-refractory prostate cancer cells (PC-3) were used as an in-vitro model system. The effect of midostaurin on cell viability was assessed by an MTT assay. Expression studies on PKC-α, PKC- d, different AP-1 transcription factors, and AP-1 regulating genes were analyzed by semiquantitative RT-PCR, and protein levels of Bcl-2 were evaluated by western blotting.

RESULTS: Midostaurin decreased the viability of hormone-refractory PC-3 cells. Furthermore, midostaurin significantly induced the transcripts of apoptotic-mediated PKC- d, tumor suppressor p53, cell cycle inhibitor p21^cip1/waf1, death receptor TNF-α, pro-apoptotic Bax, and Caspase-8, and eventually inhibited the expression of pro-survival PKC-ε, pro-oncogene c-Jun, c-Fos, Fra-1, positive growth regulator cyclin D1, and anti-apoptotic Bcl-2. In addition, midostaurin also decreased the protein expression of anti-apoptotic Bcl-2.

CONCLUSION: The present study provided evidence that midostaurin suppresses tumor growth and induces apoptosis in hormone-refractory PC-3 cells via modulation of PKC- d and PKC-ε expression, and regulation of PMA-altered c-Jun, c-Fos, and Fra-1 AP-1 transcription factors and their target genes involved in cell cycle regulation (cyclin D1, p53, p21, Bcl-2, and TNF-α). Thus, pharmacological targeting of PKC and AP-1 factors may have therapeutic potential against hormone-refractory prostate cancer.

BACKGROUND: We study the role of gonadectomy on the response to unavoidable stress and the role of testosterone replacement on gonadectomy in the male Naval Medical Research Institute mice (30±5 g) were studied. For this purpose, the hormonal and metabolic changes were investigated.

METHODS: In the experimental group, the gonads were surgically removed, and a cannula was inserted into the left lateral ventricle. For acute and chronic stress induction, animals were placed in the communication box for 30 min for one day and four consecutive days, respectively. The animals received different doses of intraventricular (ICV) testosterone (0.01, 0.05, 0.1 µg/mouse) 5 minutes or intraperitoneal (IP) testosterone (0.05, 0.01, 0.1 mg/kg) 30 minutes before the stress induction.

RESULTS: The results showed that acute and chronic stress increases plasma cortisol concentration. IP testosterone injections of testosterone did not decrease cortisol concentrations in response to acute stress, whereas ICV injections did reduce cortisol concentrations. The stress reduced anorexia time, while the administration of testosterone increased anorexia time. In addition, acute stress reduced food intake in the gonadectomized mice. IP testosterone at 0.01 and 0.05 mg/kg increased food intake. Additionally, stress in gonadectomized mice reduced water intake, while the IP injection of testosterone in chronic stress further reduced water intake. Also, stress reduced the animals’ brain/adrenal volumes, while the IP and ICV injection of testosterone at 0.01 mg/kg inhibited this effect.

CONCLUSION: The results showed that the IP (0.05, 0.01, 0.1 mg/kg) and ICV (0.01, 0.05, 0.1 µg/mouse) administration of testosterone in the gonadectomized mice can modulate hormonal and metabolic changes induced by stress.

OBJECTIVES: Thrombotic episodes occurred frequently in beta-thalassemia major (BTM) patients, leading to hypercoagulability of plasma. Protein Z (PZ) is a vitamin-K-dependent anti-coagulation factor that plays a role in the human homeostatic process. The objective of the current study is to investigate the distribution pattern of PZ plasma concentrations between BTM patients and the normal population in Ahvaz city, the center of Khuzestan province, southwest of Iran.

MATERIAL and METHODS: Forty confirmed BTM patients and 40 healthy volunteers were evaluated for complete blood count (CBC) indices and PZ plasma levels. CBC samples were measured using an automated cell counter, and PZ was assayed with an immunoassay method. Statistical analysis was conducted using SPSS software. The ROC curve and binary logistic regression estimated the sensitivity, specificity, and Odd’s ratio for PZ measurement.

RESULTS: The mean±SD of the PZ plasma level in normal individuals was 1.68±0.63 µg/mL, and in BTM patients, it was 1.10±0.52 µg/mL. This shows a significant reduction of PZ in BTM patients statistically (CI= 0.99; p<0.001). Further, the mean±SD of the PZ plasma levels in BTM patients who received washed red blood cells was not significantly different from that of patients undergoing packed red blood cell therapy (CI= 0.95; p = 0.320). The area under the curve (AUC) for PZ was 0.759 (p = 0.00). The cut-off value= 1.4 µg/mL of the PZ plasma level had at least 70% sensitivity and specificity in BTM patients.

DISCUSSION: Several epidemiologic studies have shown thromboembolism episodes in BTM patients. In the current study, PZ was reduced significantly in BTMs.

CONCLUSION: We noticed that BTMs have lower plasma PZ concentration might be predisposed to BTM.

BACKGROUND: Plant secondary metabolites act as defence molecules to protect plants from biotic and abiotic stresses. In particular, C-glycosylated flavonoids are more stable and reactive than their O-glycosylated counterparts. Therefore, vitexin (apigenin 8-C glucoside) present in Ficus deltoidea is well-known for its antioxidant, anti-inflammatory, and antidiabetic properties.

METHODS: Phenol based extraction was used to extract proteins (0.05% yield) with less plant pigments. This can be seen from clear protein bands in gel electrophoresis. In-gel trypsin digestion was subsequently carried out and analysed for the presence of peptides by LC-MS/MS.

RESULTS: Thirteen intact proteins are identified on a 12% polyacrylamide gel. The mass spectra matching was found to have 229 proteins, and 11.4% of these were involved in secondary metabolism. Proteins closely related to vitexin biosynthesis are listed and their functions are explained mechanistically. Vitexin synthesis is predicted to involve plant polyketide chalcone synthase, isomerization by chalcone isomerase, oxidation by cytochrome P450 to convert flavanone to flavone, and transfer of sugar moiety by C-glycosyltransferase, followed by dehydration to produce flavone-8-C-glucosides.

CONCLUSIONS: Phenol based extraction, followed by gel electrophoresis and LC-MS/MS could identify proteome explaining vitexin biosynthesis in F. deltoidea. Many transferases including β-1,3-galactosyltransferase 2 and glycosyl hydrolase family 10 protein were detected in this study. This explains the importance of transferase family proteins in C-glycosylated apigenin biosynthesis in medicinal plant.