Biochemistry Research International最新文献

Diabetes mellitus (DM) follows a series of metabolic diseases categorized by high blood sugar levels. Owing to the increasing diabetes disease in the world, early diagnosis of this disease is critical. New methods such as nanotechnology have made significant progress in many areas of medical science and physiology. Nanobiosensors are very sensible and can identify single virus particles or even low concentrations of a material that can be inherently harmful. One of the main factors for developing glucose sensors in the body is the diagnosis of hypoglycemia in individuals with insulin-dependent diabetes. Therefore, this study aimed to evaluate the most up-to-date and fastest glucose detection method by nanosensors and, as a result, faster and better treatment in medical sciences. In this review, we try to explore new ways to control blood glucose levels and treat diabetes. We begin with a definition of biosensors and their classification and basis, and then we examine the latest biosensors in glucose detection and new biosensors applications, including the artificial pancreas and updating quantum graphene data.

Synthetic modifications of sulfathiazole derivatives become an interesting approach to enhance their biological properties in line with their applications. As a result, sulfathiazole derivatives become a good candidate and potential class of organic compounds to play an important role towards medicinal chemistry. In present study, one thiazole derivative and two new sulfathiazole derivatives are synthesized with 94% and 72-81% yields, respectively. Furthermore, the synthesized compounds were evaluated for their in vitro antibacterial activity against two Gram-negative (E. coli and P. aeruginosa) and two Gram-positive bacterial strains (S. pyogenes and S. aureus) by disk diffusion method. Among synthesized compounds, compound 11a showed potent inhibitory activity against Gram-negative, E. coli with 11.6 ± 0.283 mm zone of inhibition compared to standard drug sulfamethoxazole (15.7 ± 0.707 mm) at 50 mg/mL. The radical scavenging activities of these compounds were evaluated using DPPH radical assay, and compound 11a showed the strongest activity with IC₅₀ values of 1.655 μg/mL. The synthesized compounds were evaluated for their in silico molecular docking analysis using S. aureus gyrase (PDB ID: 2XCT) and human myeloperoxidase (PDB ID: 1DNU) and were found to have minimum binding energy ranging from -7.8 to -10.0 kcal/mol with 2XCT and -7.5 to -9.7 with 1DNU. Compound 11a showed very good binding score -9.7 kcal/mol with both of the proteins and had promising alignment with in vitro results. Compound 11b also showed high binding scores with both proteins. Drug likeness and ADMET of synthesized compounds were predicted. The DFT analysis of synthesized compounds was performed using Gaussian 09 and visualized through Gauss view 6.0. The structural coordinates of the lead compounds were optimized using B3LYP/6-31 G (d,p) level basis set without any symmetrical constraints. Studies revealed that all the synthesized compounds might be candidates for further antibacterial and antioxidant studies.

Currently, oxidative stress is one of the major problems that threatens human health. It is at the root of many diseases such as cancer. Despite the enormous efforts provided to combat this scourge, oxidative stress is still relevant and hence comes the need for research of new remedies especially from natural origin. For this purpose, the study of the antioxidant activity of extracts of Cistus monspeliensis from Morocco is a principal research objective. The phenolic extracts were obtained by maceration of the plant in a water/acetone mixture and then separated by liquid/liquid extraction with solvents of increasing polarity. The first phytochemical tests carried out on these extracts showed the existence of different families of phenolic compounds, such as flavonoids, tannins, and others. Assays for total polyphenols, flavonoids, hydrolysable, and condensed tannins were carried out by known colorimetric methods. The results of these assays have shown that the studied extracts are rich in phenolic compounds present in the plant in the form of flavonoids (69.81 ± 0.22 mg EQ/g DM), hydrolysable tannins (61.86 ± 0.89 mg ETA/g DM), and condensed tannins (70.05 ± 1.61 mg EC/g DM). The evaluation of the antioxidant activity is carried out by two different methods: the DPPH test (2,2-DiPhenyl-1-Picryl-Hydrazyl) and the FRAP test (Ferric Reducing Antioxidant Power). The results obtained show that the extracts of Cistus monspeliensis are active and have interesting antioxidant powers. In particular, the water/acetone (WAE) (IC₅₀ = 0.079 mg/mL) and butanolic (BUE) (IC_0.5 = 0.099 mg/mL) extracts are the most active with values comparable to that of ascorbic acid. The interesting results obtained in this study clearly show that Cistus monspeliensis originating from Morocco can be considered as a source of natural antioxidants. Therefore, the extracts of this plant deserve to be tested in the medicinal field, against cancer and cardiovascular diseases, and in food field as an additive and preservative.

Alzheimer's disease manifests itself in brain tissue by neuronal death, due to aggregation of β-amyloid, produced by senile plaques, and hyperphosphorylation of the tau protein, which produces neurofibrillary tangles. One of the genetic markers of the disease is the gene that translates the presenilin-2 protein, which has mutations that favor the appearance of the disease and has no reported crystallographic structure. In view of this, protein modeling is performed using prediction and structural refinement tools followed by an energetic and stereochemical characterization for its validation. For the simulation, four reported mutations are chosen, which are Met239Ile, Met239Val, Ser130Leu, and Thr122Arg, all associated with various functional responses. From a theoretical analysis, a preliminary bioinformatic study is made to find the phosphorylation patterns in the protein and the hydropathic index according to the polarity and chemical environment. Molecular visualization was carried out with the Chimera 1.14 software, and the theoretical calculation with the hybrid quantum mechanics/molecular mechanics system from the semi-empirical method, with Spartan18 software and an AustinModel1 basis. These relationships allow for studying the system from a structural approach with the determination of small distance changes, potential surfaces, electrostatic maps, and angle changes, which favor the comparison between wild-type and mutant systems. With the results obtained, it is expected to complement experimental data reported in the literature from models that would allow us to understand the effects of the selected mutations.

Treatment of infections caused by S. aureus has become a challenge due to the emergency of resistant strains. Ozoroa reticulata root extracts have been used in traditional medicine to treat throat and chest pains in Zimbabwe. The objective of the study was to determine the effects of O. reticulata root bark extracts on the production of extracellular proteases by S. aureus. The root barks were collected, dried, and crushed into powder. To obtain different phytoconstituents, plant extractions were performed. Extractions were carried out using two solvent mixtures: ethanol : water (50 : 50 v/v) and dichloromethane : methanol (50 : 50 v/v). Serial exhaustive extractions were also performed using methanol, ethanol, dichloromethane, acetone, ethyl acetate, hexane, and water. The broth microdilution assays were used to assess the antibacterial effects of the Ozoroa reticulata root bark extracts against S. aureus. Ciprofloxacin was used as a positive control. Qualitative screening for extracellular protease production by S. aureus on BCG-skim milk agar plates using the most potent extract was carried out. The proteolytic zones were measured and expressed as the ratio of the diameter of the colony to the total diameter of the colony plus the zone of hydrolysis (P _z values). The ethyl acetate extract was found to be the most potent inhibitor of the growth of S. aureus with 99% inhibition and a minimum inhibitory concentration (MIC) of 100 µg/mL. Inhibition of extracellular protease production was directly proportional to the concentration of the extract. At 100 µg/mL, the ethyl acetate extract had a P _z value of 0.84, indicative of mild proteolytic activity. A P _z value of 0.94 was observed at a concentration of 200 µg/mL and signified weak proteolytic activity. In conclusion, the extract inhibited the production of extracellular proteases in S. aureus. Further work on the isolation and purification of bioactive compounds responsible for inhibiting the production of extracellular proteases is of importance in the discovery of agents with antivirulent effects on S. aureus.

Several studies have demonstrated that age, comorbidities, and abnormalities in different clinical biomarkers can be important to understand disease severity. Although clinical features of COVID-19 have been widely described, the assessment of alterations of the most common biochemical markers that are reported in patients with COVID-19 still has not been well established. Here, we report clinical and blood biochemical indicators of 100 patients with COVID-19. Throat-swab upper respiratory samples were obtained from patients and real-time PCR was used to confirm SARS-CoV-2 infection. Gender, age, and clinical features such as diabetes mellitus, hypertension, and smoking habits were investigated. Biochemical parameters were categorized and analyzed according to these clinical characteristics. Triglycerides, GPT, and ALP are the biochemical markers that changed the most in the group of hypertension patients. Cholesterol and triglycerides were significantly different (P=0.01; P=0.04, respectively) between diabetic and nondiabetic patients with COVID-19. Potassium levels were significantly different (P=0.03) when comparing smokers with nonsmoker patients. Our results suggest several potential biochemical indexes that changed in patients with COVID-19 and whether certain comorbidity and clinical characteristics influence these markers.

Momordica balsamina (M. balsamina) is a medicinal herb comprising health-promoting secondary metabolites. This study was aimed to profile bioactive compounds in the methanolic extract of M. balsamina leaves using molecular spectroscopic (UV-Vis and FTIR) and hyphenated chromatographic (UHPLC-qTOF-MS) techniques and evaluate the biological (in vitro anti-inflammatory and cytotoxicity) activities of the extract. The preliminary phytochemical screening tests revealed the presence of cardiac glycosides, flavonoids, saponins, tannins, and terpenoids. The UV-Vis profile revealed various absorption bands ranging from 200 to 750 nm, indicating the presence of flavonoids, phenolic compounds, tannins, terpenoids, carotenoids, chlorophyll, and alkaloids. FTIR spectra confirmed the presence of alkaloids, flavonoids, terpenes, anthraquinones, and phenolic compounds. A high-resolution and accurate mass spectrometer (LC-QTOF-MS model LC-MS-9030 instrument) was used, and the results confirmed the presence of flavonoid aglycones, such as quercetin, isorhamnetin, and kaempferol, as well as pseudolaroside A and dicaffeoylquinic and feruloyl isocitric acids. To the best of our knowledge, this is the first report of pseudolaroside A dimer and feruloyl isocitric acid in M. balsamina leaves. In vitro cytotoxicity assay showed that the extract was nontoxic against human colorectal adenocarcinoma (HT29 and Caco2), Vero, and RAW 264.7 cells. However, the extract showed anti-inflammatory activity on RAW 264.7 cells. The study confirmed that M. balsamina leaves contain nontoxic secondary metabolites that may play a pivotal role in human health as anti-inflammatory agents.

Parkinson's disease (PD) is regarded as a severe neurodegenerative disorder. Baicalein is involved in the treatment of PD. This study explored the mechanism of baicalein in PD. The PD rat model was established using 6-hydroxydopamine. The neurologic score, dopamine (DA) content, apoptotic cells, and neuronal damage were evaluated after rats were treated with baicalein. Autophagy in PD rats was inhibited using 3-methyladenine (3-MA). The mitochondrial membrane potential (MMP) and autophagy-related proteins (LC3, P62) were detected. Next, agomiR-30b was transfected into PD rats. The targeting relation between miR-30b and NIX was predicted and verified. Then, sh-NIX was transfected into PD rats, and the effects of miR-30b and NIX on MMP, LC3, and P62 were assessed. When miR-30b was overexpressed using agomiR-30b, the NIX and BNIP3 levels were detected. Baicalein increased the neurological score and restored DA content, neurons, MMP, and mitochondrial autophagy protein levels. Baicalein inhibited miR-30b expression and miR-30b targeted NIX. miR-30b upregulation or NIX silencing reversed the effect of baicalein on MMP and mitochondrial autophagy. Baicalein upregulated NIX and BNIP3 expressions, while miR-30b overexpression inhibited NIX and BNIP3 expressions. In summary, baicalein mediated mitochondrial autophagy and restored neuronal activity by downregulating miR-30b and activating the NIX/BNIP3 pathway, thus protecting against PD.

Background: Neuroblastoma is a malignant neuroendocrine tumor from the sympathetic nervous system, the most common extracranial tumor in children. Identifying potential prognostic markers of neuroblastoma can provide clues for early diagnosis, recurrence, and treatment.

Methods: RNA sequence data and clinical features of 147 neuroblastomas were obtained from the TARGET (Therapeutically Applicable Research to Generate Effective Treatments project) database. Application weighted gene coexpression network analysis (WGCNA) was used to construct a free-scale gene coexpression network, to study the interrelationship between its potential modules and clinical features, and to identify hub genes in the module. We performed Lasso regression and Cox regression analyses to identify the three most important genes and develop a new prognostic model. Data from the GSE85047 cohort verified the predictive accuracy of the prognostic model.

Results: 14 coexpression modules were constructed using WGCNA. Brown coexpression modules were found to be significantly associated with disease survival status. Multivariate Cox analysis was performed on genes from univariate Cox regression and Lasso regression analyses using the Cox proportional hazards regression model. Finally, we constructed a three-gene prognostic model: risk score = (0.003812659∗CKB) + (-0.152376975∗expDST) + (0.032032815∗expDUT). The prognosis of samples in the high-risk group was significantly poorer than that of samples in the low-risk group (P=1.225e - 06). The risk model was also regarded as an independent predictor of prognosis (HR = 1.632; 95% CI = 1.391-1.934; P < 0.001).

Conclusion: Our study constructed a neuroblastoma coexpressing gene module and identified a prognostic potential risk model for prognosis in neuroblastoma.

The aims of this study are to investigate the effect of acrylamide on the level of proinflammatory cytokines in the blood of acrylamide-treated rats and to find the modulatory impact of probiotics on those cytokines. Thirty-two rats were divided into four groups: rats which received 20 mg acrylamide, acrylamide with 20 mg probiotics, acrylamide with 200 mg probiotics, and standard water and food (groups 1-4, respectively). The serum levels of cytokines were measured on days 0, 15, and 30. Group 1 showed an increased serum level of IL-1β, IL-6, and TNF-α after 15 days, and they decreased in day 30. Serum IL-6 level was significantly decreased on days 15 and 30 in rats in group 2 compared to the controls. TNF-α and IL-1β levels were not statistically different after treated with probiotics. The exposure of rats to acrylamide led to increased systemic inflammation as evidenced by higher levels of proinflammatory cytokines, and probiotics can modulate this inflammation.