Biochemistry Research International最新文献

Eg5 is a protein encoded by KIF11 gene and is primarily involved in correct mitotic cell division. It is also involved in nonmitotic processes such as polypeptide synthesis, protein transport, and angiogenesis. The scientific literature sheds light on the ubiquitous functions of KIF11 and its involvement in the onset and progression of different pathologies. This review focuses attention on two main points: (1) the correlation between Eg5 and cancer and (2) the involvement of Eg5 in noncancerous conditions. Regarding the first point, several tumors revealed an overexpression of this kinesin, thus pushing to look for new Eg5 inhibitors for clinical practice. In addition, the evaluation of Eg5 expression represents a crucial step, as its overexpression could predict a poor prognosis for cancer patients. Referring to the second point, in specific pathological conditions, the reduced activity of Eg5 can be one of the causes of pathological onset. This is the case of Alzheimer's disease (AD), in which Aβ and Tau work as Eg5 inhibitors, or in acquired immune deficiency syndrome (AIDS), in which Tat-mediated Eg5 determines the loss of CD⁴⁺ T-lymphocytes. Reduced Eg5 activity, due to mutations of KIF11 gene, is also responsible for pathological conditions such as microcephaly with or without chorioretinopathy, lymphedema, or intellectual disability (MCLRI) and familial exudative vitreous retinopathy (FEVR). In conclusion, this review highlights the double impact that overexpression or loss of function of Eg5 could have in the onset and progression of different pathological situations. This emphasizes, on one hand, a possible role of Eg5 as a potential biomarker and new target in cancer and, on the other hand, the promotion of Eg5 expression/activity as a new therapeutic strategy in different noncancerous diseases.

Micromeria graeca L. is a dense chemical source of bioactive compounds such as phenolic compounds, which have various health-related properties. The current study aimed to investigate the impact of different extractor solvents on phenol and flavonoid contents, as well as the antioxidant and antifungal activities of different extracts. Initially, three extractor solvents (methanol, ethyl acetate, and water) were used to prepare the Soxhlet extracts, which were then examined for their polyphenolic content, flavonoid content, and antioxidant potential using three complementary assays (DPPH, FRAP, and TAC). The antifungal capacity against the two fungal strains (Candida albicans and Aspergillus niger) was performed using the method of diffusion on disc. The dosage of phytochemical compounds revealed that the highest values were established in water extract with values of 360 ± 22.1 mg GAE/g dry weight plant and 81.3 ± 21.2 mg RE/g dry weight plant for TPC and TFC, respectively. In addition, the strongest antioxidant activity measured by DPPH and FRAP assays was established in water extract with IC₅₀ values of 0.33 ± 0.23 and 0.23 ± 0.12 mg/mL, respectively, while the methanol extract showed the best antioxidant activity as measured by TAC with an IC₅₀ of 483 ± 17.6 mg GAEq/g dry weight plant. The water extract recorded the most important antifungal activity against Candida albicans with an inhibition zone of 16 ± 1.6 mm and MFC = 500 μg/mL, whereas ethyl acetate extract showed the lowest activity against both studied fungi strains. Micromeria graeca L. contains considerable amounts of bioactive contents with high antioxidant and antifungal potentials, which may make it a promising source of antioxidants and natural antifungal agents.

Bioluminescence has been a fascinating natural phenomenon of light emission from living creatures. It happens when the enzyme luciferase facilitates the oxidation of luciferin, resulting in the creation of an excited-state species that emits light. Although there are many bioluminescent systems, few have been identified. D-luciferin-dependent systems, coelenterazine-dependent systems, Cypridina luciferin-based systems, tetrapyrrole-based luciferins, bacterial bioluminescent systems, and fungal bioluminescent systems are natural bioluminescent systems. Since different bioluminescence systems, such as various combinations of luciferin-luciferase pair reactions, have different light emission wavelengths, they benefit industrial applications such as drug discovery, protein-protein interactions, in vivo imaging in small animals, and controlling neurons. Due to the expression of luciferase and easy permeation of luciferin into most cells and tissues, bioluminescence assays are applied nowadays with modern technologies in most cell and tissue types. It is a versatile technique in a variety of biomedical research. Furthermore, there are some investigated blue-sky research projects, such as bioluminescent plants and lamps. This review article is mainly based on the theory of diverse bioluminescence systems and their past, present, and future applications.

Bacterial and mammalian cells are rich in putrescine, spermidine, and spermine. Polyamines are required for optimum fitness, but the biological function of these small aliphatic compounds has only been partially revealed. Known functions of polyamines include interaction with nucleic acids that alters gene expression and with proteins that modulate activity. Although polyamines can be incorporated into proteins, very few naturally occurring polyaminated proteins have been identified, which is due in part to the difficulty in detecting these adducts. In the current study, bovine albumin and the recombinant universal stress protein from Francisella tularensis were used as models for mass spectrometry analysis of polyaminated proteins. The proteins were covalently bound to putrescine, spermidine, or spermine by the action of carbodiimide or microbial transglutaminase. Tryptic peptides, subjected to liquid chromatography tandem mass spectrometry (LC-MS/MS), were identified using Protein Prospector software. We describe the search parameters for identifying polyaminated peptides and show MS/MS spectra for adducts with putrescine, spermidine, and spermine. Manual evaluation led us to recognize signature ions for polyamine adducts on aspartate, glutamate, and glutamine, as well as neutral loss from putrescine, spermidine, and spermine during the fragmentation process. Mechanisms for the formation of signature ions and neutral loss are presented. Manual evaluation identified a false-positive adduct that had formed during trypsinolysis and resulted in peptide sequence rearrangement. Another false positive initially appeared to be a 71 kDa putrescine adduct on a cysteine residue. However, it was an acrylamide adduct on cysteine for a sample extracted from a polyacrylamide gel. The information presented in this report provides guidance and serves as a model for identifying naturally occurring polyaminated proteins.

To provide scientific evidence of the efficacy of Allium ampeloprasum against female infertility, the effects of the aqueous extract of the said plant (AE) were evaluated in rats with letrozole-induced polycystic ovary syndrome (PCOS). AE was administered orally to PCOS rats at doses of 192, 384, and 768 mg/kg. The positive control was co-treated with clomiphene citrate (1 mg/kg) and metformin (200 mg/kg). Normal and negative controls received distilled water. The vaginal contents of rats were examined daily under a microscope before (7 days) and during treatment. Treatments were administered orally for 15 days, and then, 6 rats from each group were sacrificed for biochemical and histological analyses. The remaining rats were mated with males of proven fertility for 5 days. The daily examination of vaginal smears allowed the evaluation of fertility index. After parturition, additional fertility parameters were determined. Results showed that in PCOS rats, AE decreased body weight (p < 0.001), abdominal fat weight (p < 0.001), serum levels of LH (p < 0.001), testosterone (p < 0.001), total cholesterol (p < 0.05), and LDL cholesterol (p < 0.01). HDL cholesterol increased and atherogenic indices decreased (p < 0.001). The number of Graafian follicles and corpora lutea increased, while cystic (p < 0.001) and atretic (p < 0.05) follicles decreased. AE also decreased oxidative stress in the ovaries, restored the estrous cycle, induced uterine epithelial cell hypertrophy, and improved fertility. These effects were attributed to phenols, flavonoids, terpenoids, and anthocyanins present in AE. The overall results justify the traditional use of A. ampeloprasum against female infertility and suggest its potential use as a dietary supplement for PCOS patients.

Coenzyme Q10 (CoQ10), commonly known as ubiquinone, is a vitamin-like component generated in mitochondrial inner membranes. This molecule is detected broadly in different parts of the human body in various quantities. This molecule can be absorbed by the digestive system from various nutritional sources as supplements. CoQ10 exists in three states: in a of reduced form (ubiquinol), in a semiquinone radical form, and in oxidized ubiquinone form in different organs of the body, playing a crucial role in electron transportation and contributing to energy metabolism and oxygen utilization, especially in the musculoskeletal and nervous systems. Since the early 1980s, research about CoQ10 has become the interest for two reasons. First, CoQ10 deficiency has been found to have a link with cardiovascular, neurologic, and cancer disorders. Second, this molecule has an antioxidant and free-radical scavenger nature. Since then, several investigations have indicated that the drug may benefit patients with cardiovascular, neuromuscular, and neurodegenerative illnesses. CoQ10 may protect the neurological system from degeneration and degradation due to its antioxidant and energy-regulating activity in mitochondria. This agent has shown its efficacy in preventing and treating neurological diseases such as migraine, Parkinson's disease, Alzheimer's disease, Huntington's disease, amyotrophic lateral sclerosis, and Friedreich's ataxia. This study reviews the literature to highlight this agent's potential therapeutic effects in the mentioned neurological disorders.

The level and potential of iron contained in fluted pumpkin (Telfairia occidentalis) has been exploited as a blood tonic; however, the potentials of some other parts of the plant are unknown. The effect of T. occidentalis fruit mesocarp (aqueous extract) on phenylhydrazine (PHZ)-induced anaemia in experimental rats was investigated in a bid to determine its curative properties and potential in reversing haemolytic anaemia and protection of liver health. The LD₅₀ of the fruit extract was determined using Lorke's method for the determination of acute toxicity. The study involved oral administration of varying doses of the extract to different groups of rats which were monitored for 24 hours. The test sample did not show any signs of toxicity at doses of 5000 mg/kg b.wt, which is the highest possible recommended dose for toxicity testing. For the evaluation of the effects of the fruit extract on haematological indices and biochemical enzyme markers in anaemic rats, 30 matured albino Wistar rats were used. The rats were divided into five groups of six rats each. Group 1 consisted of normal rats (control group), Group 2 consisted of anaemic untreated rats, and Group 3 consisted of anaemic rats treated with the standard drug Astymin, while Groups 4 and 5 were made up of anaemic rats given the extract at doses of 600 mg/kg b.wt and 1000 mg/kg b.wt, respectively. The fruit extract failed to show any significant effect in improving the haemoglobin (Hb), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphate (ALP) levels in anaemic rats but rather may have contributed to a reduction in Hb levels and an unhealthy increase in serum enzyme levels. This is indicative of the apparent inability of the aqueous extract of the T. occidentalis fruit mesocarp to reverse PHZ-induced haemolytic anaemia and may suggest a possible detrimental effect of high doses of the extract over a prolonged period.

Infectious diseases pose a significant threat to human health worldwide. To address this challenge, we conducted a comprehensive study on the leaf and flower extracts of Clitoria ternatea plants. Our research encompassed in vitro assessments of their antibacterial, antibiofilm, antioxidant, and cytotoxic properties. Additionally, we employed in silico screening to identify promising compounds with potential applications in developing novel anti-Escherichia coli medications. Notably, our investigation revealed a remarkable inhibition zone of 13.00 ± 1 mm when applying the leaf extract (200 μg/ml) against E. coli, showcasing its potent antibacterial properties. Furthermore, both the leaf and flower extracts exhibited substantial biofilm inhibition efficacy against S. aureus, with inhibition percentages of 54% and 58%, respectively. In the realm of antioxidant activity, the leaf and flower extracts of C. ternatea displayed noteworthy DPPH free radical scavenging capabilities. Specifically, the leaf extract exhibited a substantial activity of 62.39% at a concentration of 150 μg/ml, while the flower extract achieved 44.08% at the same concentration. Our study also evaluated the impact on brine shrimp, where the floral extract displayed a significantly higher mortality rate of 93.33% at a dosage of 200 μg/ml compared to the leaf extract. To elucidate potential therapeutic targets, we utilized molecular docking techniques, focusing on the acbR protein (5ENR) associated with antibiotic resistance in E. coli. In this analysis, compounds isolated from the C. ternatea leaf extract, namely D1 (CID-14478556), D2 (CID-6423376), and D3 (CID-20393), exhibited binding energies of -8.2 kcal/mol, -6.5 kcal/mol, and -6.3 kcal/mol, respectively. Additionally, compounds from the flower extract, E1 (CID-5282761), E2 (CID-538757), and E3 (CID-536762), displayed binding energies of -5.4 kcal/mol, -5.3 kcal/mol, and -5.1 kcal/mol, respectively. In conclusion, the leaf and flower extracts derived from C. ternatea represent a promising natural resource with potential therapeutic applications in combating antibiotic-resistant pathogens.

Despite treatments and vaccinations, it remains difficult to develop naturally occurring COVID-19 inhibitors. Here, our main objective is to find potential lead compounds from the retrieved alkaloids with antiviral and other biological properties that selectively target the main SARS-CoV-2 protease (M^pro), which is required for viral replication. In this work, 252 alkaloids were aligned using Lipinski's rule of five and their antiviral activity was then assessed. The prediction of activity spectrum of substances (PASS) data was used to confirm the antiviral activities of 112 alkaloids. Finally, 50 alkaloids were docked with M^pro. Furthermore, assessments of molecular electrostatic potential surface (MEPS), density functional theory (DFT), and absorption, distribution, metabolism, excretion, and toxicity (ADMET) were performed, and a few of them appeared to have potential as candidates for oral administration. Molecular dynamics simulations (MDS) with a time step of up to 100 ns were used to confirm that the three docked complexes were more stable. It was found that the most prevalent and active binding sites that limit M^pro'sactivity are PHE294, ARG298, and GLN110. All retrieved data were compared to conventional antivirals, fumarostelline, strychnidin-10-one (L-1), 2,3-dimethoxy-brucin (L-7), and alkaloid ND-305B (L-16) and were proposed as enhanced SARS-CoV-2 inhibitors. Finally, with additional clinical or necessary study, it may be able to use these indicated natural alkaloids or their analogs as potential therapeutic candidates.