Biochemistry Research International最新文献

[This corrects the article DOI: 10.1155/2022/6341645.].

The authors explored the genomic landscape of bat cathelicidins, critical proteins in the vertebrate innate immune system, across 41 bat species, which are notable for their high microbial tolerance. An array of bioinformatics tools, complemented by manual mining, were used to identify the curated cathelicidin sequences. Particular attention was given to the fourth exon, which is responsible for generating the biologically active peptide. This comprehensive exploration led to the identification of 72 annotated complete cathelicidins, with 44 being newly discovered. These 72 complete cathelicidin sequences, along with 7 incomplete and 4 nonfunctional sequences, result in a total of 78 peptides, 53 of which were previously unknown. These bat cathelicidins are characterized by a cathelicidin domain pfam00666, and the consensus sequence derived from aligning these domains shows a high degree of conservation in the position of each amino acid across all bat species, suggesting that they possess only one type of cathelicidin. Notably, the three-dimensional structure of the bat cathelicidin family domain closely resembles the cystatin domain previously described in Sus scrofa protegrin 3. The phylogenetic tree constructed using the bat conserved domain cluster species according to their taxonomic order, indicating the potential utility of this sequence as taxonomic markers. Finally, the authors propose a peptide classification based on three-dimensional structures and the presence or absence of the CAP18 domain, proline-rich or arginine-rich sequences. This approach holds great promise for future research focussed on precisely identifying antimicrobial peptides, conducting structure-activity and mechanism-of-action relationship studies and enhancing our understanding of the immune defence mechanisms in bats.

Objective: To study the characteristic changes in peripheral blood T-lymphocytes and their subpopulations in COVID-19 patients by in-depth characterization of peripheral blood T-lymphocytes and to analyze the changes in the severity of COVID-19 and age factors in relation to changes in T-lymphocytes and their subpopulations. Methods: T-lymphocytes (including Th cells, regulatory T-lymphocytes, CD4+ initial T-lymphocytes, CD4+ memory T-lymphocytes, CD4+ T-lymphocytes functional subsets, Tc cells, CD8+ initial T-lymphocytes, CD8+ memory T-lymphocytes, and CD8+ T-lymphocyte functional subpopulations) were isolated, by flow cytometry, from peripheral blood specimens of 60 COVID-19 patients (experimental group) and 36 healthy controls (control group). The results of the two groups were compared and further analyzed in relation to age and disease severity of COVID-19 patients. Results: The absolute counts of T-lymphocytes and their subpopulations in the peripheral blood of COVID-19 patients were reduced, and the proportions of the cells in each subpopulation were imbalanced, with the absolute counts of T-lymphocytes and their subpopulations in peripheral blood of critically ill patients being lower relative to those of mildly ill patients, and the absolute counts of CD8+ initial T-lymphocytes in the peripheral blood of COVID-19 patients group being negatively correlated with the age of the patients. Conclusion: SARS-CoV-2 infection has an inhibitory effect on the number of T-lymphocytes and the proportion of their subpopulations, especially in critically ill and elderly patients, suggesting that SARS-CoV-2 infection has a serious impact on the cellular immune function of the body, and that in-depth characterization of T-lymphocyte population can more accurately reflect the changes in immune function to assess the state of cellular immune function.

Resveratrol, often referred to as 3,4',5-trihydroxystilbene (RSV), is a compound with a variety of pharmacological benefits, such as antiaging, neuroprotective, chemopreventive, antioxidant, and anti-inflammatory qualities. To investigate neuroprotective properties of resveratrol propionate (RPE), H₂O₂ was added to SH-SY5Y cells (human neuroblastoma cell line) that had been pretreated with RPE. The modulation of Bcl-2 and Bax proteins, the mitochondrial membrane potential (MMP), cytochrome c release, the activation of caspase-9 and caspase-3, DNA fragmentation, and membrane catenin analysis were all measured in this study using flow cytometry. The protective effect of RPE pretreatment of SH-SY5Y cells on the H₂O₂-induced death process was further investigated using annexin V-fluorescein isothiocyanate (FITC). The induction of caspase-9 and caspase-3, release of cytochrome c, loss of MMP, modification of Bcl-2 and Bax, DNA fragmentation, and annexin V-FITC/PI (propidium iodide) double staining all indicate that RPEs are capable of successfully shielding SH-SY5Y cells from H₂O₂-induced cytotoxicity. Therefore, RPE is considered a good candidate for the prevention and treatment of neurodegeneration induced by oxidative damage.

Extracellular DNA of blood plasma (cell-free DNA, cfDNA) may potentially indicate a total level of apoptosis and mediate the immune response to stress induced by extreme environmental conditions, such as Antarctic wintering. We studied blood nuclease activity (NA); the content of 8-oxodG, rDNA, and SatIII(1q12) in cfDNA; and the levels of BAX, BCL2, TLR9, AIM2, STING, RIG-I, NF-kB, IL-8, and IL-17A mRNAs in 11 males, the members of the 64th Russian Antarctic Expedition. Blood was sampled before the wintering and on the 27th, 85th, 160th, 270th, and 315th days. The early months of the wintering are characterized by increased rates of apoptosis, an elevated BAX/BCL2 RNA ratio in blood leukocytes, and high cfDNA concentrations and NA in blood plasma. The properties of cfDNA are dramatically changed: the content of GC-rich rDNA rises, while AT-rich SatIII and 8-oxodG are low. We note individual multidirectional changes in the expression of TLR9 and AIM2, while STING and RIG-I are downregulated in all of the subjects. The mRNA levels of NFKB1, IL-8, and IL-17A increase dramatically, indicating immune system activation. In conclusion, (1) apoptosis is overactivated and remains elevated during the first half of the Antarctic wintering; (2) cfDNA is enriched with GC-repeats, which stimulates its biological activity; and (3) the expression of immunity genes associated with the inflammatory response is increased.

Pathogen avoidance behavior is widespread across the animal kingdom and plays an important role in animal survival in natural environments. As a free-living nematode, Caenorhabditis elegans is exposed to various microorganisms and toxic chemicals in the soil, including pathogenic bacteria and chemical toxins. C. elegans can effectively avoid pathogenic bacteria, thereby minimizing the risk of infection. However, it remains unclear whether it also exhibits avoidance behavior in response to toxic substances such as sodium arsenite. In this report, we found that as the sodium arsenite concentration in the environment increased, the arsenic content in C. elegans also increased, leading to an avoidance response. Further investigation revealed that deletion of the serotonin synthesis gene tph-1 significantly suppressed this avoidance behavior. Moreover, the expression level of TPH-1 protein in ADF neurons was significantly upregulated. Our data indicate that C. elegans exhibits a serotonin-mediated behavioral avoidance response to sodium arsenite. Additionally, we observed that the immune system of C. elegans was suppressed following sodium arsenite exposure, likely as an adaptation to the adverse environment. This study provides new insights into the strategies of C. elegans in response to toxic environmental conditions.

Capparis erythrocarpos is a medicinal plant traditionally used as an antiarthritic, anti-inflammatory, and analgesic agent. However, no previous reports exist on the analgesic and acute anti-inflammatory activities of the individual chemical constituents from this plant. This study reports the isolation, characterization, and evaluation of analgesic and acute anti-inflammatory activities of chemical constituents from the root bark of C. erythrocarpos, including their modulatory effects on TRPV1 ion channel activity. The isolated compounds were characterized as daucosterol (DC) and β-sitosterol 3-myristate (SM) using NMR and LC/GC-MS. DC significantly (p < 0.05) inhibited both phases of carrageenan-induced edema in a reverse dose-dependent manner, demonstrating 58.38% anti-inflammatory activity at 2 mg/kg p.o., comparable to diclofenac sodium (DS) at 8 mg/kg p.o. (53.07%). SM inhibited only phase 2 of carrageenan-induced edema. Both compounds significantly inhibited cold-induced pain with superior analgesic activity compared to DS. Against inflammation-induced pain, DC showed the highest analgesic activity (47.37% at 2 mg/kg p.o.). Molecular docking studies revealed that DC and SM produced ΔG values of -10.60 and -9.80 kcal/mol, respectively, which are more negative than those of DS (-8.6 kcal/mol), suggesting that they might be superior TRPV1 ion channel inhibitors and that DS likely has additional mechanisms of action. These results demonstrate that DC and SM possess remarkable therapeutic properties, warranting further exploration for novel drug development.

Tobacco smoke contains toxic chemical substances that mediate the generation of reactive oxygen species and lung cancer. This study investigates the potential of essential oils (EOs) from Juniperus oxycedrus (JOX) and Juniperus phoenicea L. (JPH) in reducing the harmful effects of cigarette smoke. The EO of JOX (JOX-EO) and JPH (JPH-EO) showed good inhibition of nicotine, with IC₅₀ values of 16.78 ± 1.04 μg/mL and 18.40 ± 0.46 μg/mL, respectively. Moreover, JOX-EO had the greatest percentage reduction of basic tar (64.45%), followed by neutral tar (53.23%), and acidic tar (25.15%). Furthermore, the evaluated JOX-EO demonstrated efficacy in inhibiting polycyclic aromatic hydrocarbons (PAHs). In vivo experiments on rats chronically exposed to cigarette smoke reveal promising results regarding oxidative stress markers. The administration of JOX-EO at 200 mg/kg for 15 days postsmoking cessation shows significant improvements in hematological variables (red blood cells [RBC], platelets [PLT], hemoglobin [HB], hematocrit [HCT], and mean corpuscular volume [MCV]). The oxidative stress markers, including glutathione (GSH), malondialdehyde (MDA), glutathione S-transferase (GST), glutathione peroxidase (GPx), and catalase (CAT), were significantly reduced, indicating powerful antioxidant potential. The EOs exhibited concentration-dependent percentage inhibition of human lung carcinoma (A549) cell viability, with IC₅₀ values indicating greater potential than etoposide, the standard used for comparison. Both EOs demonstrate the capacity to mitigate the lingering effects of smoking, such as oxidative stress and lung cancer, providing reassurance and comfort to those affected.

The global outbreak of SARS-CoV-2 has emerged as a major public health crisis due to its rapid transmission and significant morbidity and mortality rates. In response, there is an urgent need to discover novel antiviral agents targeting key viral proteins. In this study, a new series of pyrimidine-2,4-dione derivatives was synthesized from barbituric acid and its thio analog, aiming to explore their potential inhibitory activity against the SARS-CoV-2 main protease (Mpro). The synthesis involved 1,4-addition and cyclodehydration reactions, yielding novel pyran and condensed pyrimidine derivatives. The chemical structures were confirmed using various spectroscopic techniques. Molecular docking studies were performed using MOE software (version 2022) targeting Mpro (PDB ID: 6LU7), revealing favorable binding affinities for several compounds. Compound 9 showed the best docking score (-12.70 kcal/mol), followed by Compound 4 (-12.38 kcal/mol) and Compound 11 (-12.13 kcal/mol), with key interactions involving residues such as Asn142, His41, and Glu166. DFT calculations were carried out to evaluate electronic properties, including energy gap (ΔE), global hardness (η), and softness (σ), indicating that Compound 10 was the most reactive with notable HOMO-LUMO characteristics. Additionally, the synthesized compounds were screened for drug-likeness based on Lipinski's rule of five and ADME parameters. Overall, the study identifies promising pyrimidine-based inhibitors of SARS-CoV-2 Mpro and provides valuable insights for further optimization and development of potential antiviral agents.

Background: This study investigated the effect of the extractable hypoglycaemic principles from Securidaca longepedunculata leaves on some biochemical parameters in alloxan-induced diabetic rats with the view to having improved pharmacological agent(s) that could be used in managing diabetes mellitus with relatively lesser side effects. Three groups of four rats each were used for the oral glucose tolerance test (OGTT): group one received 3 mL/kg BW normal saline (normal control) while groups 2 and 3 received 200 and 400 mg/kg BW of methanol extract of Securidaca longepedunculata (MESL), respectively. Six groups of five rats per group were used for the main antidiabetic study. Group one received 3 mL/kg BW normal saline (normal control), group 2 received no treatment after induction, group 3, received 5 mg/kg BW glibenclamide (standard group), groups 3-6 received 100, 200, and 400 mg/kg BW MESL, respectively, after induction. Results: The OGTT showed significant (p < 0.05) reduction in random blood sugar of the treated groups compared to the control. In the antidiabetic study, the treated groups 4-6 significantly (p < 0.05) lowered the blood glucose of the Wistar rats compared to the treatment control. Extract administration showed no adversity to liver and kidney, respectively, as shown by result of tested standard indicators. Equally MESL caused significant (p < 0.05) increase in serum antioxidant activities and significant (p < 0.05) decrease in malondialdehyde concentration compared to the treatment control. Conclusion: The study suggested hypoglycaemic potency, antioxidant rejuvenation, and relative hepatic and nephron safety by MESL.