Biochemistry Research International最新文献

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.

In recent years, the potential of pathogenic bacteria to acquire resistance to a variety of antimicrobial drugs has developed significantly due to the indiscriminate exposure of a number of antibiotic compounds. The purpose of this study is to determine the antibacterial capabilities and activities of crude Pleurotus ostreatus extracts against Staphylococcus aureus (ATCC 25923), Escherichia coli (ATCC 25922), Neisseria gonorrhoeae (ATCC 49926), and nine multidrug-resistant clinical isolates of Neisseria gonorrhoeae. All of these isolates exhibited sensitivity to azithromycin and ceftriaxone, while the majority of antibiotic resistance was seen against penicillin G, sulphonamide, and ciprofloxacin. Fifty percent of the isolates exhibited absolute resistance to both sulphonamide and ciprofloxacin, whereas 40% of the isolates displayed absolute resistance to penicillin G. The antibacterial activity of P. ostreatus extracts examined in this investigation varied within the same species of microorganisms. Extract B and D, extracted in the presence of 20% wheat bran bagasse and 20% maize flour bagasse, respectively, had exceptional antibacterial activity against all target isolates examined. We observed the lowest concentration of antibacterial agent required to inhibit the target bacteria to be between 1 × 10^-3 mg/ml and 1 × 10^-6 mg/ml with an estimated probability of 0.30769, a lower 95% confidence interval (CI) of 0.126807, an upper 95% CI of 0.576307, an estimated probability of 0.15385, a lower 95% CI of 0.043258, and an upper 95% CI, respectively. The MBC of 1 × 10^-3 mg/ml was seen to eliminate 31% of the target bacteria. This dose was the most inhibitive. The antibacterial activity of all the extracts examined in the current study exhibited some degree of efficacy against both clinical isolates and standard strains. However, the majority of clinically isolated bacteria exhibited greater resistance to the extracts.

Objective: Oral tongue squamous cell carcinoma (OTSCC) and buccal squamous cell carcinoma (BSCC) are the first and second leading causes of oral cancer, respectively. OTSCC and BSCC are associated with poor prognosis in patients with oral cancer. Thus, we aimed to indicate signaling pathways, Gene Ontology terms, and prognostic markers mediating the malignant transformation of the normal oral tissue to OTSCC and BSCC.

Methods: The dataset GSE168227 was downloaded and reanalyzed from the GEO database. Orthogonal partial least square (OPLS) analysis identified common differentially expressed miRNAs (DEMs) in OTSCC and BSCC compared to their adjacent normal mucosa. Next, validated targets of DEMs were identified using the TarBase web server. With the use of the STRING database, a protein interaction map (PIM) was created. Using the Cytoscape program, hub genes and clusters within the PIM were shown. Next, gene-set enrichment analysis was carried out using the g:Profiler tool. Using the GEPIA2 web tool, analyses of gene expression and survival analysis were also performed.

Results: Two DEMs, including has-miR-136 and has-miR-377, were common in OTSCC and BSCC (p value <0.01; |Log2 FC| > 1). A total of 976 targets were indicated for common DEMs. PIM included 96 hubs, and the upregulation of EIF2S1, CAV1, RAN, ANXA5, CYCS, CFL1, MYC, HSP90AA1, PKM, and HSPA5 was significantly associated with a poor prognosis in the head and neck squamous cell carcinoma (HNSCC), while NTRK2, HNRNPH1, DDX17, and WDR82 overexpression was significantly linked to favorable prognosis in the patients with HNSCC. "Clathrin-mediated endocytosis" was considerably dysregulated in OTSCC and BSCC.

Conclusion: The present study suggests that has-miR-136 and has-miR-377 are underexpressed in OTSCC and BSCC than in normal oral mucosa. Moreover, EIF2S1, CAV1, RAN, ANXA5, CYCS, CFL1, MYC, HSP90AA1, PKM, HSPA5, NTRK2, HNRNPH1, DDX17, and WDR82 demonstrated prognostic markers in HNSCC. These findings may benefit the prognosis and management of individuals with OTSCC/BSCC. However, additional experimental verification is required.

Old world monkeys separated from the great apes, including the ancestor of humans, about 25 million years ago, but most of the genes in humans and various nonhuman primates are quite similar even though their anatomical appearances are quite different. Like other mammals, primates have four tropomyosin genes (TPM1, TPM2, TPM3, and TPM4) each of which generates a multitude of TPM isoforms via alternative splicing. Only TPM1 produces two sarcomeric isoforms (TPM1α and TPM1κ), and TPM2, TPM3, and TPM4 each generate one sarcomeric isoform. We have cloned and sequenced TPM1α, TPM1κ, TPM2α, TPM3α, and TPM4α with RNA from cynomolgus (Cyn) monkey hearts and skeletal muscle. We believe this is the first report of directly cloning and sequencing of these monkey transcripts. In the Cyn monkey heart, the rank order of TPM isoform expression is TPM1α > TPM2α > TPM1κ > TPM3α > TPM4α. In the Cyn monkey skeletal muscle, the rank order of expression is TPM1α > TPM2α > TPM3α > TPM1κ > TPM4α. The major differences in the human heart are the increased expression of TPM1κ, although TPM1α is still the dominant transcript. In the Cyn monkey heart, the only sarcomeric TPM isoform at the protein level is TPM1α. This is in contrast to human hearts where TPM1α is the major sarcomeric isoform but a lower quantity of TPM1κ, TPM2α, and TPM3α is also detected at the protein level. These differences of tropomyosin and/or other cardiac protein expression in human and Cyn monkey hearts may reflect the differences in physiological activities in daily life.

Several diabetic complications are associated with forming advanced glycation end products (AGEs). Different chemical and natural compounds are able to prevent the development of these products. In this study, glycosylation was induced as a model by incubating bovine serum albumin (BSA) with glucose. Consequently, BSA was treated with glucose and different concentrations (1.25, 2.5, and 5 μM) of syringic acid, gallic acid, ellagic acid, ferulic acid, paracoumaric acid, and caffeic acid for 4 and 6 weeks. Biochemical experiments comprise measurements of fluorescent AGEs, protein carbonyl contents, total thiol, hemolysis tests, and also malondialdehyde (MDA) levels in RBC. These demonstrated the antiglycating mechanism of these phenolic acids. Most of the phenolic acids used in this study reduced MDA levels and protected thiol residues in protein structures. They also inhibited the formation of fluorescent AGEs and RBC lysis, except gallic acid. Moreover, ferulic acid, paracoumaric acid, and caffeic acid proteins significantly prevent carbonylation. Molecular docking and simulation studies showed that ellagic, caffeic, gallic, and syringic acids could interact with lysine and arginine residues in the active site of BSA and stabilize its structure to inhibit the formation of AGEs. Our results suggest that phenolic acid could be used as a potential phytochemical against protein glycation and related diabetic complications.

Background: Laboratory animals are commonly fed on cereal-based diets (CBDs) whose nutrient composition is unknown and may confound the metabolic response to study interventions. Purified diets such as AIN-93M are therefore recommended, as their nutrient composition is known. However, few studies have evaluated their use as adequate control diets. The aim of this study was to compare the nutrition status of Swiss albino mice fed on either CBD or AIN-93M for 15 weeks.

Methods: Twenty Swiss albino mice aged 6-8 weeks and weighing 21.7 g ± 0.6 were fed on either CBD or AIN-93M diet for 15 weeks. Their nutritional status was evaluated using anthropometric and hematological indices, serum glucose, total protein, albumin, and total cholesterol to select an appropriate normal control diet.

Results: The CBD had low-calorie content (2.57 kcal/g) and protein (11 ± 3.8 g/100 g) compared to AIN-93M (3.8 kcal/g and 14 g/100 g, respectively). The BMI of male mice fed on CBD and AIN-93M diets was significantly higher (P=0.0139 and P=0.0325, respectively) compared to that of females fed on similar diets. Animals in the CBD group had lower hemoglobin (15.1-16.9 g/dl) compared to those in the AIN-93M group (18.1-20.8 g/dl). Serum albumin levels were higher in both male (P=0.001) and female (P=3 × 10^-6) mice fed on AIN-93M compared to those fed on CBD. Females in the AIN-93M group had higher cholesterol (P=0.026) than those in the CBD group.

Conclusion: The AIN-93 diet of caloric value 3.85 kcal/g (total protein 14 g, total fat 4 g of soy bean oil, fibre 5 g, and total carbohydrate 42 g per 100 g) can be safely used as a normal control diet in long-term research studies using Swiss albino mice.

Artemisia princeps (family Asteraceae) is a natural product broadly used as an antioxidative, hepatoprotective, antibacterial, and anti-inflammatory agent in East Asia. In the present study, eupatilin, the main constituent of Artemisia princeps, was investigated as an antihyperlipidemic agent. Eupatilin inhibited 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase (HCR), an enzyme that is a therapeutic target for hyperlipidemia, in an ex vivo assay using rat liver. In addition, oral administration of eupatilin significantly lowered the serum levels of total cholesterol (TC) and triglycerides (TG) in corn oil-induced and Triton WR-1339-induced hyperlipidemic mice. These results suggest that eupatilin can alleviate hyperlipidemia by inhibiting HCR.

Essential oils are known to possess many biological properties such as antimicrobial and antioxidant activities. Plumeria alba flowers are used in traditional remedies for diarrhea, cough, fever, and asthma treatment. This work evaluated the chemical composition and the biological activities of essential oils obtained from the flowers and leaves of Plumeria alba. The essential oils were extracted using the Clevenger-type apparatus and characterized using GC-MS. In the flower essential oil, a total of 17 compounds were identified, with linalool (23.91%), α-terpineol (10.97%), geraniol (10.47%), and phenyl ethyl alcohol (8.65%) being abundant. In the leaf essential oil, a total of 24 compounds were identified, with benzofuran, 2,3-di, hydro-(3.24%), and muurolol (1.40%) being present. Antioxidant activities were assessed using hydrogen peroxide scavenging, phosphomolybdenum, and 2, 2-diphenyl-1-picrylhydrazyl (DPPH) free radical-scavenging assays. Antimicrobial activities were assessed through a microdilution assay. The essential oil showed antimicrobial activity against test microorganisms with minimum inhibitory concentrations ranging from 25.0 to 50.0 mg/mL. Biofilm inhibition ranged from 27.14 ± 1.0 to 58.99 ± 0.6 mg/mL. The essential oil exhibited total antioxidant capacities which ranged from 17.5 μg/g AAE to 83 μg/g AAE in the phosphomolybdenum assay. The IC₅₀ values in the DPPH and hydrogen peroxide radical scavenging assays for both flowers and leaves ranged from 18.66 μg/mL to 38.28 μg/mL. Both essential oils also displayed good antibiofilm activities, with the concentration required for half-maximal inhibition of biofilm formation being ∼60 mg/mL for both oils. This study shows that essential oils of Plumeria alba possess good antioxidant and antimicrobial activities and could be used as a source of natural antioxidants and antimicrobial agents.

Background: Infertility is a common issue affecting a large number of Iraqi women of reproductive age. The relationship between vitamin D deficiency and infertility has previously drawn the attention of gynecologists, and an increasing number of vitamin D testing has been requested.

Methods: 120 women were enrolled in this study between April 2019 and April 2020. Patients were divided into two groups comprising sixty women complaining of infertility, with the other 60 women being fertile and enrolled as controls. All patients were assessed for vitamin D level.

Results: In the fertile study group, patients with deficient, insufficient, and sufficient level of vitamin were 28%, 23%, and 48%, respectively (these numbers were rounded to the nearest whole digit, as the numbers for the infertile group were given with that level of precision), whereas the infertile study group showed a statistically significant (p value = 0.002) distribution of vitamin levels with 50%, 35%, and 15% of women being deficient, insufficient, and sufficient, respectively.

Conclusions: Vitamin D is significantly deficient in infertile patients which suggests a possible, positive impact if vitamin D is considered in the management of female infertility. Further study with more participants is highly recommended.