mehr ali mahmood janlou

E-cigarettes have become popular as an alternative to traditional smoking but their long-term health effects, especially regarding cancer risk, are concerning. This review evaluates the potential carcinogenic effects of e-cigarettes, focusing on DNA damage, epigenetic changes, and tumor-promoting pathways that may promote tumor development.

A literature search on PubMed, Scopus, and Web of Science databases yielded studies on e-cigarettes and cancer risk from 2010 to 2024. The employed keywords included “e-cigarettes”, “vaping”, “cancer risk”, and “toxic chemicals”. Studies included data on e-cigarette vapor composition and health effects, excluding those on smoking cessation. Data extraction covered study design, population, e-cigarette type, usage, health outcomes, and vapor analysis. Quality was assessed using the Cochrane risk of bias tool and the Newcastle-Ottawa scale.

Research indicates that e-cigarettes can cause DNA damage and epigenetic changes that potentially lead to cancer. DNA methylation can alter gene expression and cause mutations, particularly in the respiratory system, increasing cancer risk. Short-term use of e-cigarettes induces lung cancer-related tumor-promoting factors and metastasis in small bronchial tubes. Nicotine inhalation from e-cigarettes can promote tumor growth by stimulating angiogenesis and inhibiting apoptosis, despite nicotine not being a carcinogen. E-cigarette vapor contains known carcinogens like formaldehyde and acetaldehyde, further contributing to cancer risk.

Exposure to e-cigarette vapor causes gene expression changes and epigenetic damage similar to those from combustible cigarette smoke, potentially leading to cancer. DNA methylation can change gene expression and cause mutations, especially in respiratory cells.

Context: 

Nanotechnology, specifically nanoparticles, has revolutionized cancer therapy through enhanced drug delivery, precise imaging, and accurate diagnosis. Their ability to target cancer cells directly with minimal side effects makes them especially promising for treating colorectal cancer (CRC), allowing for more effective treatments.

A systematic literature review was conducted across multiple databases (PubMed, Scopus, Embase, Cochrane, Web of Science, Google Scholar) using MeSH terms such as nanoparticles, cancer, drug delivery, and target cells. The objectives of this review were to examine the effectiveness of nanoparticle-based drug delivery systems, evaluate their targeting mechanisms, and assess their impact on treatment outcomes for CRC. Study eligibility, participant inclusion criteria, and specific intervention types were critically analyzed to ensure a comprehensive understanding.

Nanoparticle-based systems have demonstrated significant promise in shrinking tumors, improving drug accumulation at the tumor site, and facilitating easier surgical removal. These systems enhance drug efficacy, reduce toxicity, and overcome biological barriers in CRC, particularly through the use of pH-responsive and thermoresponsive nanoparticles.

The application of nanoparticles for drug delivery represents a safe and effective treatment option, demonstrating improved targeting, reduced side effects, and enhanced therapeutic outcomes. However, further research is necessary to evaluate the long-term safety, efficacy, and scalability of these systems, alongside their optimization for clinical use in personalized treatments.

Inhibition of key enzymes in bacteria that exert low evolutionary pressure can be a drug development strategy for bacterial antibiotic resistance. Sortase A (Srt A) is a transpeptidase that is widely used in site-specific protein modification. This enzyme has a key function in the interactions between Staphylococcus aureus and the host and has been considered a promising target for the drug development of resistant bacteria. To date, some Srt A inhibitors have been discovered most of them are derived from flavonoid compounds, like myricetin.

Since computational methods for monitoring the behavior of biomolecules at the microscopic level are more accurate and cost-effective, therefore, in this research, our goal is to use computational methods to find similar molecules but with higher binding and inhibitory effect than myricetin.

In this study, we used computational methods such as structure-based virtual screening, molecular docking, MM-PBSA approach, and MD simulation. A molecular docking approach was used to understand protein-ligand interactions and inhibition constants in terms of affinity. MD simulation technique was used to monitor the conformational changes of Srt A enzyme. After the MD simulation studies, the MM-PBSA approach was used to interpret the binding free energy.

First, Chemspider's chemical library was screened by the "Similarity search" method, in which myricetin was placed as a reference molecule. The second stage of screening was done using PyRx software, so that the top 10 compounds were carefully selected based on their inhibitory potential from the set of ligands obtained from the previous stage. These compounds were subjected to Autodock4.2 for molecular docking. As a result, it was observed that compound-73945561 has a higher inhibitory effect than myrsteine. To investigate the stability and efficiency of ligand binding mode, free Srt A, its complexes with myrsteine and the best selected compound were subjected to 50s molecular dynamics simulation. MD simulation results showed that compound-73945561 had better binding profiles and interactions than myrsteine as a reference inhibitor, and steadily unstable behavior was observed in the docking complex.

Overall, compound-73945561 may serve as a new inhibitor or provide a scaffold for further optimization toward the design of more potent SortA inhibitors. The development of such inhibitors would be an essential strategy against resistant bacteria.

Cefiderocol is a siderophore cephalosporin with unique cell-penetrating abilities against multidrug-resistant (MDR) Gram-negative bacteria, especially carbapenem-resistant strains. This study aimed to evaluate the prevalence and susceptibility profiles of Cefiderocol on carbapenem-resistant uropathogenic Escherichia coli and Klebsiella pneumoniae isolates among hospitalized patients.

One hundred twenty-nine patients more than 72 h admitted to hospitals participated from Feb. 2021 to Dec. 2022. Urine samples were examined to identify uropathogenic K. pneumoniae and E. coli isolates based on microscopic morphology, cultural and biochemical methods. The carbapenemase production in the isolates was evaluated using modified Hodge tests and PCR. The MIC of Cefiderocol against carbapenemase-producing isolates was evaluated according to CLSI-2021 guidelines.

According to phenotypic and genotypic tests, among forty-two E. coli isolates (71.19%) were carbapenemase positive, 38 isolates had the blaOXA gene (90.47%), and among twenty-four K. pneumoniae isolates 96% contained the blaKPC gene. In MIC determination 55.24% of carbapenem-resistant E. coli isolates were inhibited with ≤0.5 μg/ml of Cefiderocol, while only two strains (8.33%) of K. pneumoniae isolates showed resistance to the Cefiderocol (MIC90=2 μg/ml).

The present results demonstrate that the emergence of carbapenem-resistant uropathogenic bacteria poses a critical health threat to society. Based on the results, Cefiderocol demonstrated efficacy against carbapenem-resistant clinical isolates at low concentrations.

Corn is one of the valuable agricultural plants whose diversity, adaptability and high nutritional value have placed it among the most important agricultural plants in the world. Foliar spraying of nitrogen, zinc and potassium fertilizers on corn plants can provide farmers and researchers with very good information about the effect of nitrogen, zinc and potassium fertilizer consumption in the climatic conditions of Golestan province.

Considering the medicinal effects of corn cob and its importance in medicine and the presence of special effective substances in this connection in corn silk, it seems that their quantity and quality are affected by the use of nitrogen, zinc, and potassium. Therefore, examining these changes is one of the practical goals of this research.

In order to evaluate the changes resulted from nitrogen, zinc, potassium and their simultaneous application were done on some morphophysiological traits of single cross 704 hybrid maize as a randomized complete block design with four replications in spring and summer of 2019 in Golestan province, the Katoul farm. Treatments included nitrogen(N), potassium(P), zinc(Z) fertilizer and combined application of nitrogen+potassium(NP), nitrogen+zinc(NZ), potassium+zinc(PZ) and their combined application of nitrogen+potassium+zinc(NPZ) with control. The results showed the traits were affected by fertilizer sources significantly (p≤ 0.01).

The studied treatments had a significant effect on the traits of height to the first corn, number of rows, ear length and ear diameter at the time of full ripening at the probability level of (p≤ 0.01). With the application of zinc, nitrogen and potassium elements, a significant increase in the content of phenolic compounds of leaves, silk and corn seeds was observed. The flavonoids of leaves, silk and seeds were influenced by the supply of nitrogen (N), zinc (Zn), potassium (K) fertilizers and their simultaneous application. Leaf anthocyanin in foliar spraying treatments with single potassium fertilizer, due to creating optimal conditions, most of the current energy of the plant was spent in the direction of growth, development and increasing the yield of treated plants, so the biosynthesis and production of anthocyanin in corn leaves with single application of potassium was less, but silk anthocyanin And the seed with single application of potassium and simultaneous application of potassium+nitrogen, potassium+zinc, potassium+nitrogen+zinc showed a significant increase compared to the control.

according to the obtained results, the simultaneous application of fertilizers is recommended to increase the morpho-physiological traits and yield of plants.

MiR-21 is a critical small regulatory RNA involved in various cellular processes such as cell cycle, apoptosis, migration, and differentiation of stem cells. It is significantly upregulated in CRC cell lines and tissue samples, acting as a biomarker and playing an important role in the pathogenesis of CRC. MiR-21 targets and downregulates tumor suppressor genes such as PDCD4, which are part of the PI3K- mTOR pathway. The inverse relationship between miR-21 and PDCD4 expression highlights the miR-21 role in CRC progression. Research shows that miR-21 is upregulated in human CRC cell lines and tissue samples, correlating with advanced clinical stages, lymph node metastasis, and poor prognosis. This regulation highlights the potential of miR-21 as a biomarker for the early detection of CRC and as a therapeutic target for developing targeted therapies. MiR-21 regulates several CRC-related target genes, highlighting its role in cancer initiation, transformation, invasion, and metastasis. These findings provide valuable insights into miR-21's role in cancer pathogenesis and its potential clinical applications.

CP47 is one of the essential components of photosystem II (PSII) in green plants, green algae, and cyanobacteria; which is involved in the light reactions of photosynthesis. Various studies have shown that the binding of the extrinsic protein of 33 kDa (PsbO) to the large extrinsic loop of CP47 (E loop) is an essential photoautotrophic activity of the PSII complex. Moreover, the deletion of the amino acids between Gly-351 and Thr-365 within loop E failed to assemble stable PSII centers. In this study, using computational methods, the effect of Phenylalanine (Phe) mutation at position 363 on Synechocystis sp. PCC 6803 CP47 was investigated and then the mutant model was compared with the native one. Because the experimental 3D structure of Synechocystis sp. PCC 6803 CP47 and PsbO proteins are not available in the Protein Data Bank (PDB), the 3D structure of these proteins was modeled by homology modeling. After refining and energy minimization, the quality of protein geometry was assessed by different criteria such as PROCHECK and ProSA. Then, structural analysis of mutant and native models was performed with Molecular Dynamic (MD) simulation and docking method. The analysis of results obtained from MD simulation shows that F363R mutation affects the flexibility of some regions and especially leads to an increase in mutation region and changes the conformation of CP47. In addition, the results of docking studies indicate that F363R mutation can decrease buried surface area (BSA) at the interface region and decrease the binding energy of CP47 and PsbO. These data reinforce our hypothesis that an increase of flexibility at the position of F363 in the large extrinsic loop of CP47 may be an important factor in reducing interaction between CP47 and PsbO extrinsic protein and then water oxidation. oxidation.

The emergence of some mutations in the SARS-CoV-2 receptor binding domain (RBD) can increase the spread and pathogenicity due to the conformational changes and increase the stability of Spike protein. Due to the formation of different strains of SARS-CoV-2 by mutations, and their catastrophic effect on public health, the study of the effect of mutations by scientists and researchers around the world is inevitable. According to available evidence, the S494P variant is observed in several SARS-CoV-2 strains from Michigan, USA. To investigate how the S494P natural mutation alters receptor binding affinity in RBD, we performed structural analysis of wild-type and mutant spike proteins using some bioinformatics and computational tools. The results show that S494P mutation increases the spike protein stability. Also, applying docking by HADDOCK displayed higher binding affinity to hACE2 for mutant spike than wild type possibly due to the increased β-strand and Turn secondary structures which increases surface accessibly surface area (SASA) and the chance of interaction. The analysis of S494P as a critical RBD mutation may provide the continuing surveillance of spike mutations to aid in the development of COVID-19 drugs and vaccines.

In recent years, enzymatic activity of tyrosinase has been the focus of investigation due to its potential applications in medicine, agriculture and cosmetics. Tyrosinase, entitled polyphenol oxidase, is a key enzyme that catalyzes synthesis of melanin in plants, microorganisms and mammalian cells. Presence of some antioxidants can delay or inhibit the activity of this enzyme as well. In this survey, molecular docking calculation method using Autodock 4.0 software for prediction of binding energy of the protein with some antioxidant ligands was executed. The pose with the lowest energy of binding or inhibition constant was extracted at 298.15 K for kojic acid. Number of conformations in the cluster of rank was 13. The first and second boxes free energy and the inhibition constant were as follows: -5.60 kcalmol-1, 78.99 µM and -3.32 kcalmol-1, 3.66 µM, respectively. Since the first box presented a lower value of free energy, it was considered as the best mode of structure of kojic acid and the protein docking for further analysis. Thus, our present study could contribute to development and discernment of tyrosinase inhibitors in order to prevent hyper pigmentation.