A quantum mechanical investigation of nanocone oxide as a drug carrier for zidovudine: AIDS drug.

Traditionally, nanocones as a drug delivery material allow controlled drug delivery close to the target area while reducing the toxicity and generic accumulation associated with traditional intravenous injection methods. In the current study, density functional theory (DFT) is employed to investigate the therapeutic potential of carbon nanocone oxide (ONC) as a carrier with zidovudine drug for the treatment of human immunodeficiency virus (HIV). The electronic ground state and excited state were studied to evaluate the drug carrier potential of ONC and Zidovudine-ONC complex. The Frontier Molecular Orbitals (FMOs) and Molecular Electrostatic Potential (MEPs) revealed that the ONC carrier acts as a donor and zidovudine as an acceptor. The FMOs confirmed the interaction between drug and carrier stabilization energy by calculating chemical hardness, material softness, electronegativity, Ionization energy and electron affinity. The natural bond analysis (NBO), non-covalent interaction (NCI) and electron localization function (ELF) revealed the charge transfer between zidovudine and ONC. The density of state (DOS) and Charge Deposition analysis (CDA) provided the charge transfer. To study the excited state of zidovudine, transition density matrix (TDM), UV(Ultra-visible), IR (infrared), Raman, and NMR (Nuclear Magnetic Resonance) spectra of ONC and zidovudine-ONC complex have been plotted. The spectra showed a significant red shift in the zidovudine-ONC complex. Photoinduced electron studies (PET) showed fluorescence quenching because of the interaction between the drug and the carrier and provided a graphical explanation of the distinct excited state. All the results show that the ONC carrier has therapeutic potential as a zidovudine carrier for the treatment of Human Immunodeficiency Virus (HIV).

A DFT approach for finding therapeutic potential of graphyne as a nanocarrier in the doxorubicin drug delivery to treat cancer.

In the present work, the drug-loading efficacy of graphyne (GYN) for doxorubicin (DOX) drug is investigated for the first time by using density functional theory (DFT). Doxorubicin drug is effective in the cure of numerous types of cancer including bone cancer, gastric, thyroid, bladder, ovarian, breast, and soft tissue cancer. Doxorubicin drug prevents the cell division process by intercalating in the double-helix of DNA and stopping its replication. The optimized, geometrical, energetic, and excited-state characteristics of graphyne (GYN), doxorubicin drug (DOX), and doxorubicin-graphyne complex (DOX@GYN complex) are calculated to see how effective it is as a carrier. The DOX drug interacted with GYN with an adsorption-energy of -1.57 eV (gas-phase). The interaction of GYN with DOX drug is investigated using NCI (non-covalent interaction) analysis. The findings of this analysis showed that the DOX@GYN complex has weak forces of interaction. Charge transfer from doxorubicin drug to GYN during DOX@GYN complex formation is described by charge-decomposition analysis and HOMO-LUMO analysis. The increased dipole-moment (8.41 D) of the DOX@GYN in contrast with therapeutic agent DOX and GYN indicated that the drug will move easily in the biochemical system. Furthermore, the photo-induced electron-transfer process is explored for excited states, and it reveals that upon interaction, fluorescence-quenching will occur in the complex DOX@GYN. In addition, the influence of the positive and negative charge states on the GYN and DOX@GYN is also considered. Overall, the findings indicated that the GYN could be exploited as an effective drug-transporter for the delivery of doxorubicin drug. Investigators will be inspired to look at another 2D nanomaterials for drug transport applications as a result of this theoretical work.

Association Between the Site of Infection and Mortality Analysis in Critically Ill Surgical Patients.

Background Sepsis remains a critical global health concern, leading to a high mortality rate. Existing literature suggests a potential correlation between infection site and mortality. Mortality data from Pakistan, especially in the context of the infection site, is notably scarce. Purpose The study aimed to explore the relationship between the site of infection and clinical features in deceased septic patients in the surgical intensive care unit. Methods In this retrospective study conducted at the Aga Khan University Hospital, data from patients admitted to the surgical intensive care unit and meeting Sepsis 3 criteria over a five-year period (2016-2020) were analyzed. We analyzed the relation between the infection site and clinical characteristics using analysis of variance (ANOVA), chi-square, or Fisher's exact tests. Multivariable logistic regression models were applied using stepwise forward selection. A p-value of ≤ 0.05 was considered statistically significant. Results A total of 2472 ICU admissions were screened, out of which 170 patients were included in this study. Demographic analysis showed a predominantly male population with a mean age of 47 years. The most prevalent site of infection was the abdomen. Logistic regression analysis identified on-admission septic shock and high Acute Physiology and Chronic Health Evaluation (APACHE) II scores as significant risk factors for 48-hour mortality while colistimethate sodium usage and admission through the operating room were protective. Conclusion Our study provides a comprehensive analysis, outlining infection sites and identifying early mortality-influencing factors within our region. The distinct demographic profile, characterized by younger age, and the prevalence of abdominal infections in the Pakistani cohort contradict established medical literature. Early initiation of broad-spectrum antibiotics, coupled with prompt source control, confers a protective effect upon individuals afflicted with sepsis.

DFT study of therapeutic potential of graphitic carbon nitride as a carrier for controlled release of melphalan: an anticancer drug.

In the present research, the drug-delivery efficiency of graphitic carbon nitride (g-CN) for melphalan (an anti-cancer drug) was evaluated. To investigate the efficacy of g-CN as a drug-delivery system, the electronic properties of melphalan drug, g-CN, and g-CN-melphalan were calculated at the ground and excited states. The adsorption energy calculated for g-CN-melphalan complex in the water phase is - 1.51 eV. The interactions between g-CN and melphalan were investigated by a non-covalent interactions (NCl) analysis, which showed that there were weak interactions between g-CN and melphalan drug. These low intermolecular forces will allow for easy off-loading of the melphalan at the targeted site. Frontier molecular-orbitals (FMOs) analysis showed that the charge was transferred from melphalan to g-CN during the excitation process. Charge transfer was studied by charge decomposition analysis. Calculations at the excited state revealed that the g-CN-melphalan complex's λmax showed a redshift of 15 nm and 39 nm in the gas and water phase, respectively. The photoinduced electron transfer (PET) process was studied for 1-2 excited state by using electron hole theory. PET process suggests that fluorescence quenching may take place. The findings demonstrated that g-CN can be used as a drug-delivery system for melphalan drug to treat cancer. This investigation may also encourage more consideration of different 2D substances for drug delivery.

Computational study of therapeutic potential of phosphorene as a nano-carrier for drug delivery of nebivolol for the prohibition of cardiovascular diseases: a DFT study.

Density functional theory (DFT) calculations were utilized to assess the drug delivery efficiency of phosphorene carrier for nebivolol drug to treat cardiovascular diseases. The optimized structures, excited state, and electronic properties of nebivolol, phosphorene, and nebivolol-phosphorene (nebivolol-PH) complex were considered to determine the drug delivery ability of phosphorene at the target site. The increased dipole moment (6.08 D) results in the higher solubility of the complex in polar solvents (water). Weak interactive forces between nebivolol and phosphorene were demonstrated by the non-covalent interaction (NCI) plot that facilitated the offloading of nebivolol at the targeted area. The analysis of frontier molecular orbitals (FMOs) revealed that during excitation, the charge was transferred from nebivolol as a higher occupied molecular orbital (HOMO) to phosphorene as a lower unoccupied molecular orbital (LUMO). Thus, the charge-transfer process was further studied by charge decomposition analysis (CDA). The calculated results at the excited state for the nebivolol-PH complex exhibited that the maximum wavelength (λmax) was red-shifted by 6 nm in the gas phase. The electron-hole theory and photoinduced electron transfer (PET) processes were carried out for the exploration of different excited states of the complex. Additionally, phosphorene with + 1 and - 1 charge states indicated the minor structural changes and provide the stable nebivolol-PH complex. This theoretical study also investigated that phosphorene can be exploited as an effective carrier for the delivery of a therapeutic agent as nebivolol to treat cardiovascular diseases. This work will also encourage the researchers to investigate the other 2D nanoparticles as a nano-drug delivery system (NDDS).

Therapeutic potential of graphitic carbon nitride as a drug delivery system for cisplatin (anticancer drug): A DFT approach.

In the current study, for the first time; the drug loading efficacy of graphitic­carbon nitride (g-C3N4) for an anticancer drug, cisplatin was evaluated. To explore the effectiveness of g-C3N4 as a drug-delivery system, some important properties of cisplatin drug, g-C3N4 carrier, and g-C3N4-cisplatin complex were calculated at ground state and excited state. The cisplatin drug prefers to interact via H atoms to the N atoms of g-C3N4 carrier with an adsorption energy of about -1.25 eV. The type of interactions between g-C3N4 carrier molecule and cisplatin drug are visualized with the help of non-covalent interaction (NCI) analysis which demonstrated the presence of weak non-covalent interactions. These weak interactions between cisplatin drug and g-C3N4 carrier play a key role in drug-offloading at the target site. The charge-transfer process was studied with the help of HOMO-LUMO analysis and further supported by charge-decomposition analysis (CDA). Furthermore, excited-state calculations for g-C3N4-cisplatin complex revealed that λmax is red-shifted by 154 nm in the gaseous phase, and the inclusion of water results in the blue shift of λmax. Interestingly, by comparing theoretical and experimental spectra, it was found that our theoretical spectra in the solvent phase are in close agreement with experimental results. The photoinduced electron-transfer (PET) process and its effect on fluorescence phenomena, was investigated for different excited-states of g-C3N4-cisplatin complex with the help of electron-hole theory. Moreover, g-C3N4 with +1 and - 1 charge state shows negligible structural distortion and it also gives stable complexes with cisplatin drug. Overall the findings suggest that g-C3N4 could be used as an efficient drug-delivery system for the cisplatin drug to treat various types of cancer.

Altered processing enhances the efficacy of small-diameter silk fibroin vascular grafts.

Current synthetic vascular grafts are not suitable for use in low-diameter applications. Silk fibroin is a promising natural graft material which may be an effective alternative. In this study, we compared two electrospun silk grafts with different manufacturing processes, using either water or hexafluoroisopropanol (HFIP) as solvent. This resulted in markedly different Young's modulus, ultimate tensile strength and burst pressure, with HFIP spun grafts observed to have thicker fibres, and greater stiffness and strength relative to water spun. Assessment in a rat abdominal aorta grafting model showed significantly faster endothelialisation of the HFIP spun graft relative to water spun. Neointimal hyperplasia in the HFIP graft also stabilised significantly earlier, correlated with an earlier SMC phenotype switch from synthetic to contractile, increasing extracellular matrix protein density. An initial examination of the macrophage response showed that HFIP spun conduits promoted an anti-inflammatory M2 phenotype at early timepoints while reducing the pro-inflammatory M1 phenotype relative to water spun grafts. These observations demonstrate the important role of the manufacturing process and physical graft properties in determining the physiological response. Our study is the first to comprehensively study these differences for silk in a long-term rodent model.

Genetic Divergence and Diversity in Himalayan Puccinia striiformis Populations from Bhutan, Nepal, and Pakistan.

The western Himalayan region in Pakistan has been shown to be the center of diversity of Puccinia striiformis; however, little is known about its genetic relations with the eastern part of the Himalayas. We studied the genetic structure of P. striiformis from Nepal (35 isolates) and Bhutan (31 isolates) in comparison with 81 Pakistani samples collected during 2015 and 2016, through microsatellite genotyping. Genetic analyses revealed a recombinant and highly diverse population structure in Pakistan, Bhutan, and Nepal. A high level of genotypic diversity (>0.90) was observed for the three countries of Pakistan (0.96), Bhutan (0.96), and Nepal (0.91) with the detection of 108 distinct multilocus genotypes (MLGs) in the overall population; 59 for Pakistan, 27 for Bhutan, and 26 for Nepal. Mean number of alleles per locus and gene diversity were higher in Nepal (3.19 and 0.458, respectively) than Bhutan (3.12 and 0.458, respectively). A nonsignificant difference between the observed and the expected heterozygosity in all populations further confirmed the recombinant structure. A clear population subdivision between the Himalayan region of Nepal, Bhutan, and Pakistan was evident, as revealed by FST values (ranging between 0.111 to 0.198), discriminant analysis of principal components, and resampling of MLGs. Limited gene flow could be present between Nepal and Bhutan, while the population from Pakistan was clearly distinct, and no divergence was present between two populations from Pakistan (Bajaur and Malakand). The overall high diversity and recombination signature suggested the potential role of recombination in the eastern Himalayan region (Nepal and Bhutan), which needs to be considered during host resistance deployment and in the context of aerial dispersal of the pathogen. Further surveillance should be made in the Himalayan region for disease management in the region and in the context of worldwide invasions.

DFT study of the therapeutic potential of phosphorene as a new drug-delivery system to treat cancer.

In this study, the therapeutic potential of phosphorene as a drug-delivery system for chlorambucil to treat cancer was evaluated. The geometric, electronic and excited state properties of chlorambucil, phosphorene and the phosphorene-chlorambucil complex were evaluated to explore the efficiency of phosphorene as a drug-delivery system. The nature of interaction between phosphorene and chlorambucil is illustrated through a non-covalent interaction (NCI) plot, which illustrated that weak forces of interaction are present between phosphorene and chlorambucil. These weak intermolecular forces are advantageous for an easy offloading of the drug at the target. Frontier molecular orbital analysis revealed that charge was transferred from chlorambucil to phosphorene during excitation from the HOMO to LUMO. The charge transfer was further supplemented by charge-decomposition analysis (CDA). Excited-state calculations showed that the λ max was red-shifted by 79 nm for the phosphorene-chlorambucil complexes. The photo-induced electron-transfer (PET) process was observed for different excited states, which could be well explained visually based on the electron-hole theory. The photo-induced electron transfer suggests that a quenching of fluorescence occurs upon interaction. This study confirmed that phosphorene possesses significant therapeutic potential as a drug-delivery system for chlorambucil to treat cancer. This study will also motivate further exploration of other 2D materials for drug-delivery applications.