An early diagnosis of lung and colon cancer (LCC) is critical for improved patient outcomes and effective treatment. Histopathological image (HSI) analysis has emerged as a robust tool for cancer diagnosis. HSI analysis for a LCC diagnosis includes the analysis and examination of tissue samples attained from the LCC to recognize lesions or cancerous cells. It has a significant role in the staging and diagnosis of this tumor, which aids in the prognosis and treatment planning, but a manual analysis of the image is subject to human error and is also time-consuming. Therefore, a computer-aided approach is needed for the detection of LCC using HSI. Transfer learning (TL) leverages pretrained deep learning (DL) algorithms that have been trained on a larger dataset for extracting related features from the HIS, which are then used for training a classifier for a tumor diagnosis. This manuscript offers the design of the Al-Biruni Earth Radius Optimization with Transfer Learning-based Histopathological Image Analysis for Lung and Colon Cancer Detection (BERTL-HIALCCD) technique. The purpose of the study is to detect LCC effectually in histopathological images. To execute this, the BERTL-HIALCCD method follows the concepts of computer vision (CV) and transfer learning for accurate LCC detection. When using the BERTL-HIALCCD technique, an improved ShuffleNet model is applied for the feature extraction process, and its hyperparameters are chosen by the BER system. For the effectual recognition of LCC, a deep convolutional recurrent neural network (DCRNN) model is applied. Finally, the coati optimization algorithm (COA) is exploited for the parameter choice of the DCRNN approach. For examining the efficacy of the BERTL-HIALCCD technique, a comprehensive group of experiments was conducted on a large dataset of histopathological images. The experimental outcomes demonstrate that the combination of AER and COA algorithms attain an improved performance in cancer detection over the compared models.

Introduction: Rhein, a natural bioactive lipophilic compound with numerous pharmacological activities, faces limitations in clinical application due to poor aqueous solubility and low bioavailability. Thus, this study aimed to develop a rhein-loaded self-nano emulsifying drug delivery system (RL-SNEDDS) to improve solubility and bioavailability. Methods: The RL-SNEDDS was prepared by aqueous titration method with eucalyptus oil (oil phase), tween 80 (surfactant), and PEG 400 (co-surfactant) and optimization was performed by 3² factorial design. The optimized formulation was characterized for Fourier transform infrared spectroscopy, differential scanning calorimetry, powdered X-ray diffraction, and Field emission scanning electron microscopy. Further, the oral bioavailability study and brain tissue pharmacokinetics study were performed on Sprague-Dawley rats. Results: The optimized RL-SNEDDS had an average droplet size of 129.3 ± 1.57 nm, zeta potential of − 24.6 mV ± 0.34, % transmittance of 94.82 ± 0.61, and encapsulation efficiency of 98.86 ± 0.23. Furthermore, RL-SNEDDS was transformed into solid RL-SNEDDS (RS-SNEDDS) to increase stability. In vitro release of rhein from RS-SNEDDS showed prolonged release up to 24h with 99.03± 1.04% drug release. Differential scanning calorimetry and powdered X-ray diffraction analysis confirmed the reduction in drug crystallinity and supported the results of the dissolution study. Field emission scanning electron microscopy analysis revealed the smooth and spherical nanosized globule of SNEDDS. Moreover, the in vivo pharmacokinetic study showed a significantly higher (p ≤ 0.05) value of C_max and AUC_0-t of RS-SNEDDS (8 ± 0.930 μg/mL and 37.79 ± 2.01 μg/mL*hr) compared to free rhein suspension (1.96 ± 0.712 μg/mL and 7.32 ± 0.946 μg/mL*hr) which indicated the enhancement of bioavailability of RS-SNEDDS. We also examined the C_max and AUC_0-t of RS-SNEDDS in the brain and it was found to be 2.90 ± 0.171 μg/mL and 18.18 ± 1.68 μg/mL*hr respectively. Conclusion: This study concludes that the RS-SNEDDS improves brain tissue concentration and oral bioavailability, both of which increase therapeutic potential.

Brain metastasis is one of the major reasons of death in breast cancer (BC) patients, significantly affecting the quality of life, physical activity, and interdependence on several individuals. There is no clear evidence in scientific literature that depicts an exact mechanism relating to brain metastasis in BC patients. The tendency to develop breast cancer brain metastases (BCBMs) differs by the BC subtype, varying from almost half with triple-negative breast cancer (TNBC) (HER2⁻ ER⁻ PR⁻), one-third with HER2⁺ (human epidermal growth factor receptor 2-positive, and around one-tenth with luminal subclass (ER⁺ (estrogen positive) or PR⁺ (progesterone positive)) breast cancer. This review focuses on the molecular pathways as possible therapeutic targets of BCBMs and their potent drugs under different stages of clinical trial. In view of increased numbers of clinical trials and systemic studies, the scientific community is hopeful of unraveling the underlying mechanisms of BCBMs that will help in designing an effective treatment regimen with multiple molecular targets.

Innovative drug delivery systems based on iron oxide nanoparticles (INPs) has generated a lot of interest worldwide and have prime biomedical benefits in anticancer therapy. There are still issues reported regarding the stability, absorption, and toxicity of iron oxide nanoparticles (INPs) when administered due to its rapid surface oxidation and agglomeration with blood proteins. To solve this problem, we have synthesized trehalose-coated stabilized iron oxide nanoparticles (TINPs) by a co-precipitation technique. The surface coating of INPs with trehalose helps to improve the stability, prevents protein binding, and increase absorption uptake inside the body. Developed TINPs was then loaded with anticancer drug cytarabine by chemical crosslinking encapsulation method using suitable solvent. Engineered cytarabine-loaded trehalose-coated stabilized iron oxide nanoparticles (CY-TINPs) were optimized for particle size, zeta potential (−13.03 mV), and solid-state characterization such as differential scanning calorimetry (DSC), X-ray powder diffraction (XRD), and transmission electron microscope (TEM) studies. The particle size of 50 nm was achieved for developed CY-TINPs. The developed CY-TINPs was further evaluated for in vitro cell line investigations which confirmed potential cytotoxic activity. Developed CY-TINPs show remarkable enhancement in in vivo pharmacokinetic parameters C_max as 425.26 ± 2.11 and AUC_0–72 as 11,546.64 ± 139.82 as compared to pure drug. Compared to traditional drug delivery, the CY-TINPs formulation can effectively delay release, improve bioavailability, and boost cytotoxic activity against tumors.

Cardiovascular diseases (CVD) cause significant global morbidity, mortality and public health burden annually. CVD alters richness, diversity, and composition of Gut microbiota along with RAS and histopathological differences. Present study explores Metformin role in mitigating doxorubicin induced cardiovascular toxicity/remodeling. Animals were divided into 4 groups with n=6: Group I (N. Control) free access to diet and water; Group II (MET. Control) on oral Metformin (250 mg/kg) daily; Group III (DOX. Control) alternate day intraperitoneal Doxorubicin (3 mg/kg) totaling 18 mg/kg; Group IV (DOX. MET. Control) received both daily oral Metformin (250 mg/kg) and alternate day Doxorubicin (3 mg/kg). Gut microbial analysis was made from stool before animals were sacrificed for biochemical and histopathological analysis. Significant alterations were observed in ɑ and β-diversity with new genus from Firmicutes, specifically Clostridia_UCG-014, Eubacterium ruminantium, and Tunicibacter, were prevalent in both the DOX. Control and DOX.MET groups. Proteobacteria, represented by Succinivibrio, were absent in all groups. Additionally, Parabacteroides from the Bacteroidia phylum was absent in all groups except the N. control. In the DOX.MET Control group, levels of Angiotensin II ( 7.75± 0.49 nmol/min, p<0.01) and Renin (2.60±0.26 ng/ml/hr) were significantly reduced. Conversely, levels of CK-MB, Fibrinogen, Troponin, CRP ( p < 0.0001), and TNFɑ (p < 0.05) were elevated. Histopathological examination revealed substantial cardiac changes, including Fibrinogen and fat deposition and eosinophilic infiltration, as well as liver damage characterized by binucleated cells and damaged hepatocytes, along with altered renal tissues in the DOX.MET.Control group. The findings suggest that MET. significantly modifies gut microbiota, particularly impacting the Firmicutes and Proteobacteria phyla. The reduction in Angiotensin II levels, alongside increased inflammatory markers and myocardial damage, highlights the complex interactions and potential adverse effects associated with MET therapy on cardiovascular health.

The administration of hinokitiol, a natural bioactive compound with promising therapeutic potential, particularly against breast cancer, faces notable challenges related to its poor solubility and low bioavailability, limiting its clinical applications. The present study aimed to advance a previously developed liquid hinokitiol‐loaded phytosomal formulation by incorporating it into 3D‐printed oral tablets using a REGEMAT 3D Bioprinter, containing either pure drug or drug‐loaded phytosomes to enhance the pharmacokinetic performance and therapeutic efficacy of this compound. The tablets were formulated using hydroxypropyl methylcellulose‐based paste and subjected to comprehensive quality control tests, including weight variation, thickness, drug content, friability, and in vitro dissolution. Scanning electron microscopy revealed that the phytosome‐loaded tablets had a denser, waxy‐like appearance with fewer voids, which contributed to improved drug release profiles. Molecular docking and molecular dynamics simulations revealed strong and stable interactions between hinokitiol and target proteins, providing insight into the potential anticancer activity of this compound through hydrogen bonding with DNA guanine 19 and hydrophobic interactions with residues such as Trp‐1510, Leu‐1513, and Met‐1533. In vitro dissolution experiments showed faster and more complete drug release from phytosome‐loaded tablets compared with those containing pure hinokitiol. Pharmacokinetic evaluation in male Wistar rats revealed the superior performance of phytosome‐loaded tablets, with a higher maximum plasma concentration and greater area under the curve. These results highlight the potential of 3D‐printed tablets with hinokitiol‐loaded phytosomes as a novel drug delivery system that significantly improves the bioavailability, drug release, and therapeutic efficacy of hinokitiol. The integration of nanotechnology and 3D printing in the present study offers a promising platform for enhancing the clinical utilization of bioactive compounds with poor solubility, such as hinokitiol.