Identification of Helicobacter pylori-carcinogenic TNF-alpha-inducing protein inhibitors via daidzein derivatives through computational approaches.

Gastric cancer is considered a class 1 carcinogen that is closely linked to infection with Helicobacter pylori (H. pylori), which affects over 1 million people each year. However, the major challenge to fight against H. pylori and its associated gastric cancer due to drug resistance. This research gap had led our research team to investigate a potential drug candidate targeting the Helicobacter pylori-carcinogenic TNF-alpha-inducing protein. In this study, a total of 45 daidzein derivatives were investigated and the best 10 molecules were comprehensively investigated using in silico approaches for drug development, namely pass prediction, quantum calculations, molecular docking, molecular dynamics simulations, Lipinski rule evaluation, and prediction of pharmacokinetics. The molecular docking study was performed to evaluate the binding affinity between the target protein and the ligands. In addition, the stability of ligand-protein complexes was investigated by molecular dynamics simulations. Various parameters were analysed, including root-mean-square deviation (RMSD), root-mean-square fluctuation (RMSF), radius of gyration (Rg), hydrogen bond analysis, principal component analysis (PCA) and dynamic cross-correlation matrix (DCCM). The results has confirmed that the ligand-protein complex CID: 129661094 (07) and 129664277 (08) formed stable interactions with the target protein. It was also found that CID: 129661094 (07) has greater hydrogen bond occupancy and stability, while the ligand-protein complex CID 129664277 (08) has greater conformational flexibility. Principal component analysis revealed that the ligand-protein complex CID: 129661094 (07) is more compact and stable. Hydrogen bond analysis revealed favourable interactions with the reported amino acid residues. Overall, this study suggests that daidzein derivatives in particular show promise as potential inhibitors of H. pylori.

Structural, thermodynamic, and magnetic properties of SrFe12O19 hexaferrite modified by co-substitution of Cu and Gd.

A hard magnetic system of SrFe12O19 nanomaterial was modified according to the composition of Sr0.95Gd0.05Fe12-xCuxO19 with x = 0.0, 0.30, and 0.60 using the sol-gel technique. The structures of the samples were evaluated using X-ray diffraction (XRD) along with Rietveld refinement, and an M-type hexaferrite with a hexagonal structure was confirmed with a trace amount of the α-Fe2O3 phase. In addition, transmission electron microscopy (TEM) analysis revealed polycrystalline nanoplates in all samples. Furthermore, the bond structures of the octahedral and tetrahedral sites along with the thermodynamic properties of these ferrites were extracted from the FTIR spectra at room temperature. The Debye temperature (θD) decreased from 755.9 K to 749.3 K due to the co-substitution of Gd3+ at Sr2+ and Cu2+ at Fe3+. The magnetic hysteresis (M-H) measurements revealed that the coercivity decreased from 5.3 kOe to 1.5 kOe along with the highest magnetization saturation (Ms) of 65.2 emu g-1 for the composition Sr0.95Gd0.05Fe11.7Cu0.3O19, which is suitable for industrial application. The effect of local crystalline anisotropy in magnetization was explored using the law of approach to saturation (LAS). Finally, thermo-magnetization was recorded in the range from 400 K to 5 K for cooling under zero field and in the presence of a 100 Oe field, and magnetic transitions were tracked due to the introduction of the foreign atoms of Gd and Cu into SrFe12O19.

Vitamin D deficiency and the vitamin D receptor (VDR) gene polymorphism rs2228570 (FokI) are associated with an increased susceptibility to hypertension among the Bangladeshi population.

Vitamin D receptor (VDR) gene is implicated in hypertension vulnerability due to its role in regulating the renin-angiotensin system (RAS) and blood pressure. In this case-control study, a carefully selected cohort of 111 hypertensive individuals and 100 healthy controls underwent serum analysis using HPLC to measure 25-hydroxy vitamin D levels. Polymorphic variations in the VDR gene were detected and characterized using the PCR-RFLP method. At first, lower 25-hydroxy vitamin D levels were observed in hypertensive individuals compared to controls (p<0.001). The genotype frequency of the VDR gene TaqI showed no significant difference between cases and controls (p>0.05). Similarly, no significant difference was found in the VDR gene BsmI genotype frequency between hypertensive patients and controls (p>0.05). However, a statistically significant distinction was observed in the VDR gene FokI genotype frequency between cases and controls (p<0.01). The odds ratios for FokI genotypes (CC, CT, TT, and CT+TT) were 1.0, 0.590, 1.566, and 0.963, respectively. Furthermore, serum 25-hydroxy vitamin D levels were significantly higher in control subjects compared to hypertensive patients across all genotypes of VDR (p<0.001). Hypertensive patients, excluding those with the FokI VDR gene CC genotype, exhibited significantly higher systolic blood pressure levels compared to the control group (p<0.05). Similarly, hypertensive subjects displayed elevated diastolic blood pressure levels compared to the control group (p<0.001). Overall, the results suggest the presence of a potential inverse correlation between serum 25-hydroxy vitamin D levels and hypertension. The association analysis conducted indicated that there is no significant association between TaqI and bsmI genotypic variants and the risk of developing hypertension. However, it was observed that VDR gene polymorphisms do have a clear association with hypertension susceptibility, as evidenced by the significantly higher occurrence of FokI genotypic variants in hypertensive patients. Our study therefore introduces the possibility of utilizing 25-hydroxy vitamin D deficiency and VDR gene polymorphisms as a biomarker for hypertension.

Corrigendum: Anti-viral drug discovery against monkeypox and smallpox infection by natural curcumin derivatives: a computational drug design approach.

[This corrects the article DOI: 10.3389/fcimb.2023.1157627.].

Anti-viral drug discovery against monkeypox and smallpox infection by natural curcumin derivatives: A Computational drug design approach.

Background: In the last couple of years, viral infections have been leading the globe, considered one of the most widespread and extremely damaging health problems and one of the leading causes of mortality in the modern period. Although several viral infections are discovered, such as SARS CoV-2, Langya Henipavirus, there have only been a limited number of discoveries of possible antiviral drug, and vaccine that have even received authorization for the protection of human health. Recently, another virial infection is infecting worldwide (Monkeypox, and Smallpox), which concerns pharmacists, biochemists, doctors, and healthcare providers about another epidemic. Also, currently no specific treatment is available against Monkeypox. This research gap encouraged us to develop a new molecule to fight against monkeypox and smallpox disease. So, firstly, fifty different curcumin derivatives were collected from natural sources, which are available in the PubChem database, to determine antiviral capabilities against Monkeypox and Smallpox. Material and method: Preliminarily, the molecular docking experiment of fifty different curcumin derivatives were conducted, and the majority of the substances produced the expected binding affinities. Then, twelve curcumin derivatives were picked up for further analysis based on the maximum docking score. After that, the density functional theory (DFT) was used to determine chemical characterizations such as the highest occupied molecular orbital (HOMO), lowest unoccupied molecular orbital (LUMO), softness, and hardness, etc. Results: The mentioned derivatives demonstrated docking scores greater than 6.80 kcal/mol, and the most significant binding affinity was at -8.90 kcal/mol, even though 12 molecules had higher binding scores (-8.00 kcal/mol to -8.9 kcal/mol), and better than the standard medications. The molecular dynamic simulation is described by root mean square deviation (RMSD) and root-mean-square fluctuation (RMSF), demonstrating that all the compounds might be stable in the physiological system. Conclusion: In conclusion, each derivative of curcumin has outstanding absorption, distribution, metabolism, excretion, and toxicity (ADMET) characteristics. Hence, we recommended the aforementioned curcumin derivatives as potential antiviral agents for the treatment of Monkeypox and Smallpox virus, and more in vivo investigations are warranted to substantiate our findings.

Exploring the Therapeutic Effect of Neurotrophins and Neuropeptides in Neurodegenerative Diseases: at a Glance.

Neurotrophins and neuropeptides are the essential regulators of peripheral nociceptive nerves that help to induce, sensitize, and maintain pain. Neuropeptide has a neuroprotective impact as it increases trophic support, regulates calcium homeostasis, and reduces excitotoxicity and neuroinflammation. In contrast, neurotrophins target neurons afflicted by ischemia, epilepsy, depression, and eating disorders, among other neuropsychiatric conditions. Neurotrophins are reported to inhibit neuronal death. Strategies maintained for "brain-derived neurotrophic factor (BDNF) therapies" are to upregulate BDNF levels using the delivery of protein and genes or compounds that target BDNF production and boosting BDNF signals by expanding with BDNF mimetics. This review discusses the mechanisms of neurotrophins and neuropeptides against acute neural damage as well as highlighting neuropeptides as a potential therapeutic agent against Parkinson's disease (PD), Huntington's disease (HD), Alzheimer's disease (AD), and Machado-Joseph disease (MJD), the signaling pathways affected by neurotrophins and their receptors in both standard and diseased CNS systems, and future perspectives that can lead to the potent application of neurotrophins and neuropeptides in neurodegenerative diseases (NDs).

Multifaceted role of natural sources for COVID-19 pandemic as marine drugs.

COVID-19, which is caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has quickly spread over the world, posing a global health concern. The ongoing epidemic has necessitated the development of novel drugs and potential therapies for patients infected with SARS-CoV-2. Advances in vaccination and medication development, no preventative vaccinations, or viable therapeutics against SARS-CoV-2 infection have been developed to date. As a result, additional research is needed in order to find a long-term solution to this devastating condition. Clinical studies are being conducted to determine the efficacy of bioactive compounds retrieved or synthesized from marine species starting material. The present study focuses on the anti-SARS-CoV-2 potential of marine-derived phytochemicals, which has been investigated utilizing in in silico, in vitro, and in vivo models to determine their effectiveness. Marine-derived biologically active substances, such as flavonoids, tannins, alkaloids, terpenoids, peptides, lectins, polysaccharides, and lipids, can affect SARS-CoV-2 during the viral particle's penetration and entry into the cell, replication of the viral nucleic acid, and virion release from the cell; they can also act on the host's cellular targets. COVID-19 has been proven to be resistant to several contaminants produced from marine resources. This paper gives an overview and summary of the various marine resources as marine drugs and their potential for treating SARS-CoV-2. We discussed at numerous natural compounds as marine drugs generated from natural sources for treating COVID-19 and controlling the current pandemic scenario.

Investigation on structure, thermodynamic and multifunctional properties of Ni-Zn-Co ferrite for Gd3+ substitution.

This study presents a modification of structure-dependent elastic, thermodynamic, magnetic, transport and magneto-dielectric properties of a Ni-Zn-Co ferrite tailored by Gd3+ substitution at the B-site replacing Fe3+ ions. The synthesized composition of Ni0.7Zn0.2Co0.1Fe2-x Gd x O4 (0 ≤ x ≤ 0.12) crystallized with a single-phase cubic spinel structure that belongs to the Fd3̄m space group. The average particle size decreases due to Gd3+ substitution at Fe3+. Raman and IR spectroscopy studies illustrate phase purity, lattice dynamics with cation disorders and thermodynamic conditions inside the studied samples at room temperature (RT = 300 K). Ferromagnetic to paramagnetic phase transition was observed in all samples where Curie temperature (T C) decreases from 731 to 711 K for Gd3+ substitution in Ni-Zn-Co ferrite. In addition, Gd3+ substitution reinforces to decrease the A-B exchange interaction. Temperature-dependent DC electrical resistivity (ρ DC) and temperature coefficient of resistance (TCR) have been surveyed with the variation of the grain size. The frequency-dependent dielectric properties and electric modulus at RT for all samples were observed from 20 Hz to 100 MHz and the conduction relaxation processes were found to spread over an extensive range of frequencies with the increase in the amount of Gd3+ in the Ni-Zn-Co ferrite. The RLC behavior separates the zone of frequencies ranging from resistive to capacitive regions in all the studied samples. Finally, the matching impedance (Z/η 0) for all samples was evaluated over an extensive range of frequencies for the possible miniaturizing application.

Antidiabetic and hypolipidemic effects of different fractions of Coccinia cordifolia L. on normal and streptozotocin-induced diabetic rats.

The present study was carried out to observe the antidiabetic and hypolipidemic effects of petroleum-ether, ethyl acetate and chloroform fractions isolated from ethanolic extract of the leaves of Coccinia cordifolia Linn. (150 mg/kg body weight) on normal and streptozotocin (STZ)-induced diabetic rats for one day experiment. Single doses (150 mg/kg, i.p.) of C. cordifolia extracts were given to normal and diabetic rats. The fasting blood glucose (FBG), serum triglyceride (TG) and serum total cholesterol (TC) levels were investigated in normal and STZ-diabetic rats on 0, 1, 2, 3, 6, 10, 16, and 24th hours. In normoglycemic rats the pet-ether and ethyl acetate fractions of C. cordifolia reduced blood glucose level significantly (39.66% and 40.68% at 16th and 24th hour respectively). In the STZ-diabetic rats pet-ether and ethyl acetate fractions also reduced blood glucose level significantly (50.39% and 50% at 10th and 24th hour respectively). Ethyl acetate fraction is most effective which reduced total cholesterol level by 31.04% and 36.69% in normal and STZ-diabetic rats respectively. Ethyl acetate fraction reduced triglyceride level by 43.82% and 42.01% in normal and STZ-diabetic rats respectively. Our results indicate that pet-ether and ethyl acetate fractions of C. cordifolia have potentiality against diabetes.

Oral glucose tolerance test (OGTT) in normal control and glucose induced hyperglycemic rats with Coccinia cordifolia l. and Catharanthus roseus L.

The aim of this study is to investigate the hypoglycemic effects of petroleum ether, chloroform and ethyl acetate fractions isolated from ethanolic extracts of Coccinia cordifolia and Catharanthus roseus on normal control and orally glucose-induced hyperglycemic rats. Single doses (150 mg/kg) of different fractions of C. cordifolia and C. roseus extracts were intraperitonelly administered. The serum blood glucose level was obtained by pricking the tail vein using glucometer at time 0, 30, 60, 90, 150 and 270 minutes. In the orally glucose induced hyperglycemic rats, chloroform-coccinia (CHCl3-CC) fraction showed maximum reduction of blood glucose level by 21.94% on 60 minute of the experiment. On the other hand maximum reduction (p<0.05) of 17.92% was observed for petroleum ether-catharanthus (PET-CR) on 30 minute of the experiment. Metformin HCl was used as standard drug. Our results indicate that the CHCl3-CC fraction is relatively more potent than other fractions of C. cordifolia. Similarly the PET-CR is found to be better than other fractions of catharanthus. Phytochemical screening test results showed that chloroform fraction of C. cordifolia contain saponins and flavonoids compounds, which are known to be hypoglycemic. On the other hand petroleum ether fraction of C. roseus contains tannins, flavonoids and alkaloid compounds produced varying degree of blood sugar reduction. On the pharmacological point of view C. cordifolia and C. roseus appears to be a valuable plant, which can be useful, at least as an adjunct, in the therapy of diabetes.