Therapeutic potential of ethoxy mansonone G: A comprehensive exploration of its anticancer actions in breast cancer, colorectal cancer, and non-small cell lung carcinoma.

Mansonone G (MG), a 1,2-naphthoquinones with antiestrogenic, antimicrobial, and anti-adipogenic activities, is derived from the heartwood of Mansonia gagei Drumm. Ethoxy mansonone G (EMG), an essential derivative of MG, has anticancer and antioxidant agent. EMG also has antiestrogen activity and is demonstrated to lower estrogen receptor expression in endocrine-resistant cells. EMG significantly inhibits cell division, invasion, and anchorage-dependent growth in all cancer types. Through the stimulation of the tumor protein (p53) and extracellular signal-regulated kinase (ERK) signaling cascades, it also causes apoptosis. Moreover, it manifests its anti-cancerous effects in toll-like receptor pathways, c-Jun N-terminal kinase (c-JNK), and nuclear factor kappa B (NF-κB). EMG inhibits the phosphorylation of glycogen synthase kinase (GSK3), Erk, protein kinase B (Akt), and mammalian target of rapamycin (mTOR). By interfering with molecular cascades, EMG significantly reduces the metabolism of cancer cells. This paper focuses on the potential use of EMG in cancer treatment. Moreover, it states the methodology by which specific assays establish the anti-cancerous role of EMG. Breast cancer, non-small cell lung cancer, and colorectal cancer are only a few of the cancers for which EMG was shown to be effective. Through further research, EMG may be developed as a therapeutic solution to complications caused by cancer. This study presents EMG as a novel candidate for cancer therapy, offering a unique combination of pharmacological advantages and mechanistic insights that warrant further exploration and development toward addressing the complexities of cancer treatment.

Cytotoxic, Anti-inflammatory, and Leishmanicidal Activities of Diterpenes Isolated from the Roots of Caesalpinia pulcherrima.

A phytochemical investigation on the chloroform extract of Caesalpinia pulcherrima roots led to the isolation of ten known furanocassane diterpenoids, vouacapen-5α-ol (1), 8,9,11,14-didehydrovouacapen-5α-ol (2), 6ß-cinnamoyl-7ß-hydroxyvouacapen-5α-ol (3), pulcherrin A (4), pulcherrin B (5), pulcherrin J (6), pulcherrimin A (7), pulcherrimin B (8), pulcherrimin C (9), and pulcherrimin E (10). Chemical transformation of 3 and 7 gave compounds 6ß-hydroxyisovouacapenol C (11), 6ß-cinnamoyl-7ß-acetoxyvouacapen-5α-ol (12), and pulcherrimin D (13). Cytotoxicity of compounds 1-13 was evaluated against three cancer cell lines (MCF-7, HeLa, and PC-3). Anti-inflammatory potential of the compounds was evaluated via the oxidative burst assay using a luminol-amplified chemiluminescence technique. Leishmanicidal activity was tested against promastigotes of Leishmania major in vitro. Compounds 3, 4, 8, 9, and 10 were found active against all three cancer cell lines with IC50s ranging from 7.02 ± 0.31 to 36.49 ± 1.39 µM. Compounds 8 and 13 exhibited a potent inhibitory effect on reactive oxygen species generated from human whole blood phagocytes (IC50 = 15.30 ± 1.10 µM and 8.00 ± 0.80 µM, respectively). Compounds 3, 9, and 13 showed significant activity against promastigotes of L. major (IC50 = 65.30 ± 3.20, 58.70 ± 2.80, and 55.90 ± 2.40 µM, respectively).

Ginger ring compounds as an inhibitor of spike binding protein of alpha, beta, gamma and delta variants of SARS-CoV-2: An in-silico study.

The available drugs against coronavirus disease 2019 (COVOD-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), are limited. This study aimed to identify ginger-derived compounds that might neutralize SARS-CoV-2 and prevent its entry into host cells. Ring compounds of ginger were screened against spike (S) protein of alpha, beta, gamma, and delta variants of SARS-CoV-2. The S protein FASTA sequence was retrieved from Global Initiative on Sharing Avian Influenza Data (GISAID) and converted into ".pdb" format using Open Babel tool. A total of 306 compounds were identified from ginger through food and phyto-databases. Out of those, 38 ring compounds were subjected to docking analysis using CB Dock online program which implies AutoDock Vina for docking. The Vina score was recorded, which reflects the affinity between ligands and receptors. Further, the Protein Ligand Interaction Profiler (PLIP) program for detecting the type of interaction between ligand-receptor was used. SwissADME was used to compute druglikeness parameters and pharmacokinetics characteristics. Furthermore, energy minimization was performed by using Swiss PDB Viewer (SPDBV) and energy after minimization was recorded. Molecular dynamic simulation was performed to find the stability of protein-ligand complex and root-mean- square deviation (RMSD) as well as root-mean-square fluctuation (RMSF) were calculated and recorded by using myPresto v5.0. Our study suggested that 17 out of 38 ring compounds of ginger were very likely to bind the S protein of SARS-CoV-2. Seventeen out of 38 ring compounds showed high affinity of binding with S protein of alpha, beta, gamma, and delta variants of SARS-CoV-2. The RMSD showed the stability of the complex was parallel to the S protein monomer. These computer-aided predictions give an insight into the possibility of ginger ring compounds as potential anti-SARS-CoV-2 worthy of in vitro investigations.

Presence of T3SS (exoS, exoT, exoU and exoY), susceptibility pattern and MIC of MDR-Pseudomonas aeruginosa from burn wounds.

INTRODUCTION: The emergence of resistance is a major public health and clinical issue, particularly in pathogens causing nosocomial infections. Recently, there is the emergence of Pseudomonas aeruginosa resistance to different broad-spectrum antibiotics. METHODOLOGY: The current study was designed to find out the prevalence of multi-drug resistant (MDR) P. aeruginosa in burn patients, the antibiotic susceptibility pattern of MDR Pseudomonas, and to determine the Minimum Inhibitory Concentration (MIC) of the effective antimicrobials. The assessment of virulence genes (exoT, exoS, exoY and exoU) was also achieved through PCR. In the current study wound swabs were collected from 160 burn patients from two burn units (MTI-Govt. Lady Reading Hospital and MTI-Khyber Teaching Hospital). RESULTS: Out of these 160 samples, 26 samples (16.25%) were positive for P. aeruginosa. Per patients, one isolate was included in the current study. Antibiotic susceptibility pattern showed all P. aeruginosa isolates were 100% resistant to amoxicillin-clavulanic acid, 84.62% resistance to Cefepime, and Ceftazidime, and 76.92% resistance to Amikacin, Aztreonam, and Ciprofloxacin. Whereas the lowest resistance was observed to Imipenem and Piperacillin-Tazobactam (53.85%), Colistin Sulfate (23.08%), and Polymyxin-B (15.38%). Regarding the prevalence of MDR, 22 (84.61%) isolates out of 26 were found to be MDR-P. aeruginosa. For MDR-P. aeruginosa, the MIC range was 1-2 µg/mL against Polymyxin-B, 2-8 µg/mL against Colistin sulfate, 16-1024 µg/mL against Imipenem and 128-1024 µg/mL against Piperacillin-Tazobactam. 100% of the isolates carried exoT, 88.46% carried exoY, and 57.69% and 38.46% carried exoU and exoS, respectively. CONCLUSIONS: These findings further emphasize the need for antibiotic discipline and to follow the recommended hospital antibiotic policy to prevent the proliferation of MDR strains of P. aeruginosa in the community.

Elucidation of correlation between SARS-CoV-2 RdRp and N gene cycle threshold (Ct) by RT-PCR with age and gender.

BACKGROUND: Coronavirus disease 2019 (COVID19) caused by the new severe acute respiratory syndrome coronavirus 2 (SARSCoV2) is a global public health emergency. Age and gender are two important factors related to the risk and outcome of various diseases. Cycle threshold (Ct) value is believed to have relation with age and gender. OBJECTIVE: This study has been conducted to investigates the association between SARS-CoV-2 cycle threshold to age and gender of COVID-19 patients, to investigate whether the population-wide change of SARSCoV2 RTPCR Ct value over time is corelated to the number of new COVID19 cases and to investigate the dynamic of RdRp and N genes. METHODS: 72,811 individuals from second wave of COVID19, were observed in current study at Pure Health Lab, Mafraq Hospital, Abu Dhabi, UAE. RESULTS: 15,201/72,811 (21 %) positivity was observed. COVID-19 were more prevalent in males (59.35%) as compared to female (40.65%). The Positivity rate were significantly higher in Male than in Female cases (p-Value = 0.04). The Ct values for both targets of all the samples were ranged from 4.57 to 29.73. Longitudinal analysis showed significant increased during the study period from starting to end as were hypothesized. Interestingly, both the targets (RdRp and N) were present in age < 1 year. Which may indicate that mutated strains are not prevalent in children's < 1 year. CONCLUSION: There was no statistically significant difference in viral loads in between age-groups. Males were tending to higher viral load compared to females. The findings have implications for preventive strategies.

Eplerenone nanocrystals engineered by controlled crystallization for enhanced oral bioavailability.

Poor aqueous solubility of eplerenone (EPL) is a major obstacle to achieve sufficient bioavailability after oral administration. In this study, we aimed to develop and evaluate eplerenone nanocrystals (EPL-NCs) for solubility and dissolution enhancement. D-optimal combined mixture process using Design-Expert software was employed to generate different combinations for optimization. EPL-NCs were prepared by a bottom-up, controlled crystallization technique during freeze-drying. The optimized EPL-NCs were evaluated for their size, morphology, thermal behavior, crystalline structure, saturation solubility, dissolution profile, in vivo pharmacokinetics, and acute toxicity. The optimized EPL-NCs showed mean particle size of 46.8 nm. Scanning electron microscopy revealed the formation of elongated parallelepiped shaped NCs. DSC and PXRD analysis confirmed the crystalline structure and the absence of any polymorphic transition in EPL-NCs. Furthermore, EPL-NCs demonstrated a 17-fold prompt increase in the saturation solubility of EPL (8.96 vs. 155.85 µg/mL). The dissolution rate was also significantly higher as indicated by ∼95% dissolution from EPL-NCs in 10 min compared to only 29% from EPL powder. EPL-NCs improved the oral bioavailability as indicated by higher AUC, Cmax, and lower Tmax than EPL powder. Acute oral toxicity study showed that EPL-NCs do not pose any toxicity concern to the blood and vital organs. Consequently, NCs prepared by controlled crystallization technique present a promising strategy to improve solubility profile, dissolution velocity and bioavailability of poorly water-soluble drugs.