One of the most promising drugs recently approved for the treatment of various types of cancer is dacomitinib, which belongs to the tyrosine kinase inhibitor class. The US Food and Drugs Administration (FDA) has recently approved dacomitinib as a first-line treatment for patients suffering from non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutations. The current study proposes the design of a novel spectrofluorimetric method for determining dacomitinib based on newly synthesized nitrogen-doped carbon quantum dots (N-CQDs) as fluorescent probes. The proposed method is simple and does not require pretreatment or preliminary procedures. Since the studied drug does not have any fluorescent properties, the importance of the current study is magnified. When excited at $325 \mathrm{nm}$, N-CQDs exhibited native fluorescence at $417 \mathrm{nm}$, which was quantitatively and selectively quenched by the increasing concentrations of dacomitinib. The developed method involved the simple and green microwave-assisted synthesis of N-CQDs, using orange juice as a carbon source and urea as a nitrogen source. The characterization of the prepared quantum dots was performed using different spectroscopic and microscopic techniques. The synthesized dots had consistently spherical shapes and a narrow size distribution and demonstrated optimal characteristics, including a high stability and a high fluorescence quantum yield ($25.3\%$). When assessing the effectiveness of the proposed method, several optimization factors were considered. The experiments demonstrated highly linear quenching behavior across the concentration range of $1.0-20.0 \mathsf{\mu }\mathrm{g}/\mathrm{mL}$ with a correlation coefficient (r) of 0.999. The recovery percentages were found to be in the range of 98.50–100.83% and the corresponding relative standard deviation (%RSD) was 0.984. The proposed method was shown to be highly sensitive with a limit of detection (LOD) as low as $0.11 \mathsf{\mu }\mathrm{g}/\mathrm{mL}$. The type of mechanism by which quenching took place was also investigated by different means and was found to be static with a complementary inner filter effect. For quality purposes, the assessment of the validation criteria adhered to the ICHQ2(R1) recommendations. Finally, the proposed method was applied to a pharmaceutical dosage form of the drug (Vizimpro^® Tablets) and the obtained results were satisfactory. Considering the eco-friendly aspect of the suggested methodology, using natural materials to synthesize N-CQDs and water as a diluting solvent added to its greenness profile.

A hemorrhagic fever caused by the Marburg virus (MARV) belongs to the Filoviridae family and has been classified as a risk group 4 pathogen. To this day, there are no approved effective vaccinations or medications available to prevent or treat MARV infections. Reverse vaccinology‐based approach was formulated to prioritize B and T cell epitopes utilizing a numerous immunoinformatics tools. Potential epitopes were systematically screened based on various parameters needed for an ideal vaccine such as allergenicity, solubility, and toxicity. The most suitable epitopes capable of inducing immune response were shortlisted. Epitopes with population coverage of 100% and fulfilling set parameters were selected for docking with human leukocyte antigen molecules, and binding affinity of each peptide was analyzed. Finally, 4 CTL and HTL each while 6 B cell 16‐mers were used for designing multiepitope subunit (MSV) and mRNA vaccine joined via suitable linkers. Immune simulations were used to validate the constructed vaccine’s capacity to induce a robust immune response whereas molecular dynamics simulations were used to confirm epitope‐HLA complex stability. Based on these parameter’s studies, both the vaccines constructed in this study offer a promising choice against MARV but require further experimental verification. This study provides a rationale point to begin with the development of an efficient vaccine against Marburg virus; however, the findings need further experimental validation to confirm the computational finding of this study.

Diabetic polyneuropathy is characterized by structural abnormalities, oxidative stress, and neuroinflammation. The current study aimed to determine the antinociceptive effects of isoeugenol and eugenol and their combinations in neuropathic pain resulting from streptozotocin (STZ)-induced diabetes and neuroinflammation. Female SD rats were categorized into normal control, diabetic control, and treatment groups. On the 28th day and 45th day, behavioral studies (allodynia and hyperalgesia) were performed to analyze the development and protection of diabetic polyneuropathy. The levels of inflammatory and oxidative mediators, such as superoxide dismutase (SOD), tumor necrosis factor-α (TNF-α), catalase, reduced glutathione, and thiobarbituric acid reactive substances (TBARS), were estimated. In addition, the level of nerve growth factor (NGF) was estimated at the end of the study in different groups. The anti-NGF treatment decreased its upregulation in the dorsal root ganglion significantly. The results showed that isoeugenol, eugenol, and their combination have therapeutic potential against neuronal and oxidative damage induced by diabetes. In particular, both compounds significantly affected behavioral function in treated rats and showed neuroprotection against diabetic neuropathy, and their combination had synergistic effects.

Fourier transform infrared spectroscopy (FTIR) has been shown to be a promising tool for identifying the mode of action of drugs. However, most previous studies have focused on the analysis of fixed or dried cells. The measurement of living cells has the advantage of obtaining time series data, and the in situ approach eliminates the need for fixing or drying the cells. In this study, the potential of live-cell FTIR method for the identification of the mode of action of drugs was demonstrated. Four different drugs were tested, with two of the drugs having the same mode of action (tamoxifen and toremifene) and the other two having different modes of action (imatinib and doxorubicin). Live cells were treated in the four drugs at and below the IC₅₀ level (i.e. the concentration of drug required to inhibit the growth of cells by 50%), and the changes to their spectra after the addition of drugs were monitored over a 24-hour period. Principal component analysis (PCA) of the spectral data shows that drugs with different modes of action are well-separated, while the drugs with the same mode of action are grouped together. The results also show that at IC₅₀, the separation appears to be the clearest at 2 hours for imatinib and tamoxifen/toremifene and 6 hours for doxorubicin. However, at 50% of the IC₅₀ drug concentration, the separation appears to be the best at longer incubation time, i.e. 24 hours, for all four drugs. In conclusion, live-cell FTIR has shown to be able to distinguish and group spectral signatures of cells treated with drugs of known modes of action after a relatively short time of exposure. Further collection of live-cell data would enable an algorithm to be developed for the prediction of the modes of action of novel drugs, which can help in the preclinical drug screening process.

Background: Europinidin is a derivative of delphinidin obtained from the plants Plumbago Europea and Ceratostigma plumbaginoides. This herb has wide medicinal applications in treating various diseases but there are very few studies available on this bioactive compound. Considering this background, the present study is designed for the evaluation of Europinidin against Parkinson’s disease. Aim: The investigation aims to assess the effect of Europinidin in the rotenone-activated Parkinson’s paradigm. Methods: To evaluate neuroprotective activity, rotenone (1.5 mg/kg s.c) and europinidin (10 mg/kg and 20 mg/kg) was administered in rats for 21 days. The behavioural parameters were performed before sacrificing the rats. On the 22nd day, all the rats were assessed for biochemical markers (SOD, GSH, MDA, Catalase), neurotransmitter levels (Dopamine, 5-HIAA, DOPAC, and HVA levels), and neuroinflammatory markers (IL-6, IL-1β and TNF-α). Results: It was found that rotenone produced significant (p < 0.001) oxidative damage, a cholinergic deficit, dopaminergic loss, and a rise in neuroinflammatory markers in rats. Conclusion: The study concludes that europinidin possesses anti-oxidant and anti-inflammatory properties. The results suggest the therapeutic role of europinidin against rotenone-activated behavioural, biochemical, and neuroinflammatory alterations in rats.