Cutaneous leishmaniasis (CL) is a neglected public health problem in developing countries including Iran. CL is caused by different species of Leishmania parasites and results in morbidity and complications in patients with active lesions. Since protozoa are intracellular parasites, cellular immunity plays an essential role in controlling the infection. Cellular immunity is induced immediately after the infection and persists for many years after recovery. Studies over the past decades have identified the important role of CD4+ T cells and their T-helper subtypes in the immune response to CL. Finding antigens capable of producing Th1-dominant immune responses can play an effective role in preventing CL. This study examines the protective role of PHOSPHOENOLPYRUVATE CARBOXYKINASE (PEPCK), a critical enzyme for protozoan survival and reproduction. The potential of targeting PEPCK for the development of novel prevention strategies against Chagas disease is explored. Detailed findings presented herein underscore the critical role of PEPCK as an immunogenic antigen in parasite metabolism, gluconeogenesis, and energy homeostasis. Notably, the elimination of PEPCK alters parasite metabolic activity and attenuates Leishmania pathogenicity. These results position PEPCK as a promising vaccine candidate and therapeutic target for CL, pending further validation.Cutaneous leishmaniasis (CL) is a neglected public health problem in developing countries including Iran. CL is caused by different species of Leishmania parasites and results in morbidity and complications in patients with active lesions. Since protozoa are intracellular parasites, cellular immunity plays an essential role in controlling the infection. Cellular immunity is induced immediately after the infection and persists for many years after recovery. Studies over the past decades have identified the important role of CD4+ T cells and their T-helper subtypes in the immune response to CL. Finding antigens capable of producing Th1-dominant immune responses can play an effective role in preventing CL. This study examines the protective role of PHOSPHOENOLPYRUVATE CARBOXYKINASE (PEPCK), a critical enzyme for protozoan survival and reproduction. The potential of targeting PEPCK for the development of novel prevention strategies against Chagas disease is explored. Detailed findings presented herein underscore the critical role of PEPCK as an immunogenic antigen in parasite metabolism, gluconeogenesis, and energy homeostasis. Notably, the elimination of PEPCK alters parasite metabolic activity and attenuates Leishmania pathogenicity. These results position PEPCK as a promising vaccine candidate and therapeutic target for CL, pending further validation.

A gene of interest in this study is PHOSPHOENOLPYRUVATE CARBOXYKINASE (pepck), encoding a protein with a substantial role in the gluconeogenesis pathway and in metabolism of nitrogenous compounds in developing seeds of legumes, including amides and ureides which are then transformed into amino acids necessary for the synthesis of storage proteins. Whereas studies on genes contributing to the seed filling in chickpea and its protein content might be valuable in engineering plants with seeds of a higher nutritional value. In order to investigate pepck gene expression in different genotypes of chickpea (Cicer arietinum L.), four genotypes of chickpea were studied by Real-time PCR and western blot techniques. So results show that pepck expresses in high protein genotypes more than low protein genotypes at different growth stages and there was a differential expression of pepck gene at different stages of flowering and seed development. The PEPCK was expressed at higher levels during the shoot formation and in developing seeds compared to the flowering and seed formation stages.

PHOSPHOENOLPYRUVATE CARBOXYKINASE (PEPCK) has been shown to be present in plants and animals, playing different metabolic roles in different tissues. The basic role of this enzyme is its contribution in the gluconeogenesis pathway. Evidences have shown that PEPCK may play a role in metabolism of nitrogenous compounds in developing seeds of legumes. In this research, pepck gene expression and the occurrence of PEPCK protein and its activity in different genotypes of chickpea (Cicer arietinume L.) were determined. Two low protein genotypes (MCC291 & MCC373) and two high protein genotypes (MCC458 & MCC053) out of 20 chickpea genotypes were selected, from which the total RNA was extracted through different stages of seed development. The expression of chickpea pepck gene was estimated by semi-quantitative RT-PCR. The results of RT-PCR showed that two isoforms of this gene were expressed in high protein genotypes, whereas in the low protein genotypes were not expressed. The differential expression of pepck gene is perhaps related to the possible role of Phosphoenolpyrovate CARBOXYKINASE in protein content of chickpea seeds.

PHOSPHOENOLPYRUVATE CARBOXYKINASE (PEPCK) catalyzes the first step of the gluconeogenesis cycle. There are two isozymes forms of this enzyme, cytosolic PHOSPHOENOLPYRUVATE CARBOXYKINASE (PEPCK-C) and mitochondrial PHOSPHOENOLPYRUVATE CARBOXYKINASE (PEPCK-M) which present in mitochondria and cytoplasm Current research has been conducted to identify the allelic polymorphism in the PEPCK-M gene in breeder hens of native fowls and commercial broiler and layer chickens. Blood samples were collected randomly from 150 birds of three strains and DNA was extracted using modified salting out method. A fragment of 401 bp in length was amplified from exon 9 of PEPCK-M gene. For genotyping of each sample the PCR products were digested by AccI restriction enzyme. The frequency of AccI- and AccI+allele was estimated at 0.73 and 0.27 in native fowls population, 0.6 and 0.4 in broiler and 0.85 and 0.15 in layer lines, respectively. Two genotypes of AccI -/- and AccI -/+were observed with the frequency of 0.46 and 0.54 in native fowls, 0.20 and 0.80 in broiler line and 0.70 and 0.30 in commercial layer line, respectively. The comparison of allelic frequency showed no statistical differences between native fowls population with broiler and layer lines, but this results indicated significantly differences between broiler and layer lines (P<0.05).The comparison of genotypic frequency showed that there were significant differences between three populations (P<0.05). No any AccI+/+genotype was detected in the genotyped samples. The difference in genotypic distribution may be as a consequence of different selection strategies used in these populations.

The bacterial PHOSPHOENOLPYRUVATE (PEP): sugar phosphotransferase system (PTS) mediates the uptake and phosphorylation of carbohydrates, and is involved in signal transduction. It comprises two general phosphotransferase proteins (EI and HPr) and a—species dependent—variable number of sugar-specific enzyme II complexes (IIA, IIB, IIC). EI and HPr transfer phosphoryl groups from PEP to the IIA units. IIA and IIB sequentially transfer phosphates to the sugar, which is translocated by the IIC unit. The ratio of phosphorylated to non-phosphorylated IIA and IIB varies with transport activity, and the phosphorylation state of some of the IIA and IIB serves as signal input for regulation of catabolite repression, intermediate metabolism, gene expression and chemotaxis in response to the availability of carbohydrates and PEP (glycolytic activity). PTS occur in about one-third of all eubacteria and in a few archaebacteria but not in animals and plants. Uniqueness and pleiotropic function make the PTS a potential target for anti-infectives. The PTS transporter for mannose is utilized as a gate for the penetration of bacteriophage lambda DNA across, and insertion of certain bacteriocins (small antimicrobial peptides) into the inner membrane. The PTS of Escherichia coli is in the focus of this review, but occasionally comparisons with other species are made. The topics are: History; Modular design of the E. coli PTS; Structure function and catalytic mechanism of the protein modules; Regulation of and by the PTS; the PTS in pathogenicity and virulence; Computational models; Metabolic engineering.

Background: Diabetes is a dangerous metabolic disorder that is becoming more common worldwide. In the present research, we aimed to analyze the chemical composition, in silico molecular docking, and evaluate the biological features of Salvia mirzayanii. Materials and Methods: The constituents found in the aqueous extract of S. mirzayanii leaves were identified using gas chromatography–mass spectrometry (GC-MS). The major compounds of S. mirzayanii extract were subjected to molecular docking analysis. Screening for potential antioxidant abilities was conducted using radical scavenging assays. Alpha-amylase and α-glucosidase inhibitory kinetic studies were performed to evaluate the in vitro antihyperglycemic potential of S. mirzayanii. The in vivo function of S. mirzayanii extract was evaluated by examining the gene expression of PHOSPHOENOLPYRUVATE CARBOXYKINASE (PEPCK), glucose 6-phosphatase (G6Pase), and glucose transporter-4 (GLUT4) in diabetic rats. Results: The major compounds in aqueous extract of S. mirzayanii were 1, 8-cineole (51. 6 + 2. 7%), linalool acetate (22. 0 + 1. 9%), a-terpinyl acetate (9. 3 + 0. 7%), and aromadendrene (5. 6 + 0. 6). In silico studies indicated that 1, 8-cineole was a more potent inhibitor of α-amylase and α-glucosidase enzymes. The liquid extract of S. mirzayanii showed considerable radical scavenging activity against 2, 2-diphenyl-1-picrylhydrazyl (DPPH) and effective inhibition of α-amylase (IC50 = 0. 01 ± 0. 02) and α-glucosidase (IC50 = 0. 11 ± 0. 01). The highest antihyperglycemic activity was observed with a 600 mg/kg dose of the plant’s aqueous extract. Conclusions: Altogether, our findings show the possibility of applying the aqueous extract of S. mirzayani leaves as a potential therapeutic compound.

2Background and Aim: One of the important and effective physiological systems in the pathogenesis of type 2 diabetes is the local renin-angiotensin system. The aim of the current study was to determine the effect of aerobic exercise on the function of the local renin-angiotensin system and the gluconeogenesis pathway in the liver tissue of type 2 diabetic rats. Methods: In this experimental study, 18 rats were fed a high-fat diet (HFD) for 8 weeks, and then they developed type 2 diabetes by injecting a single dose of streptozotocin and HFD for four weeks. After the induction of type 2 diabetes, the rats were randomly divided into two groups: 1. diabetes-non-exercise group, 2. diabetes-exercise group. Rats in the exercise group trained 5 days/week, 45 minutes/session for 8 weeks on a treadmill with a mean speed of 20 meters per minute. Blood was collected from rats and liver tissue was extracted and frozen in liquid nitrogen to check the expression of angiotensin II, PHOSPHOENOLPYRUVATE CARBOXYKINASE (PEPCK), At1 receptor and Mass receptor genes. Results: Results of the present study showed that HFD consumption and streptozotocin injection increased blood glucose in rats (P=0.001). The ANOVA test showed that eight weeks of aerobic training caused a significant decrease in the expression of angiotensin II (P=0.001), PEPCK (P=0.003), At1 receptor (P=0.001) genes and the amount of blood glucose (P=0.002) in diabetes-exercise rats compared to diabetes-non-exercise group. Moreover, aerobic training led to a significant increase in the expression of Mass receptor (P=0.001) in diabetes-exercise rats compared to diabetes-non-exercise group. Conclusion: Eight weeks of aerobic exercise can improve insulin sensitivity and type 2 diabetes by reducing angiotensin II, At1 receptor gene expression, inhibiting hepatic gluconeogenesis and increasing Mass receptor activity.