Drug repurposing a compelling cancer strategy with bottomless opportunities: Recent advancements in computational methods and molecular mechanisms.

Drug discovery has customarily focused on a de novo design approach, which is extremely expensive and takes several years to evolve before reaching the market. Discovering novel therapeutic benefits for the current drugs could contribute to new treatment alternatives for individuals with complex medical demands that are safe, inexpensive, and timely. In this consequence, when pharmaceutically yield and oncology drug efficacy appear to have hit a stalemate, drug repurposing is a fascinating method for improving cancer treatment. This review gathered about how in silico drug repurposing offers the opportunity to quickly increase the anticancer drug arsenal and, more importantly, overcome some of the limits of existing cancer therapies against both old and new therapeutic targets in oncology. The ancient nononcology compounds' innovative potential targets and important signaling pathways in cancer therapy are also discussed. This review also includes many plant-derived chemical compounds that have shown potential anticancer properties in recent years. Here, we have also tried to bring the spotlight on the new mechanisms to support clinical research, which may become increasingly essential in the future; at the same time, the unsolved or failed clinical trial study should be reinvestigated further based on the techniques and information provided. These encouraging findings, combined together, will through new insight on repurposing more non-oncology drugs for the treatment of cancer.

The neglected continuously emerging Marburg virus disease in Africa: A global public health threat.

Background and Aim: Severe viral hemorrhagic fever (VHF) is caused by Marburg virus which is a member of the Filoviridae (filovirus) family. Many Marburg virus disease (MVD) outbreaks are reported in five decades. A major notable outbreak with substantial reported cases of infections and deaths was in 2022 in Uganda. The World Health Organisation (WHO) reported MVD outbreak in Ghana in July 2022 following the detection of two probable VHF patients there. Further, the virus was reported from two other African countries, the Equatorial Guinea (February 2023) and Tanzania (March 2023). There have been 35 deaths out of 40 reported cases in Equatorial Guinea, and six of the nine confirmed cases in Tanzania so far. Methods: Data particularly on the several MVD outbreaks as reported from the African countries were searched on various databases including the Pubmed, Scopus, and Web-of-science. Also, the primary data and reports from health agencies like the WHO and the Centers for Disease Control and Prevention CDC) were evaluated and the efficacy reviewed. Results: Chiroptera in general and bat species like Rousettus aegyptiacus and Hipposideros caffer in particular are natural reservoirs of the Marburg virus. MVD-infected nonhuman primate African fruit-bat and the MVD-infected humans pose significant risk in human infections. Cross-border viral transmission and its potential further international ramification concerns raise the risk of its rapid spread and a potential outbreak. Occurrence of MVD is becoming more frequent in Africa with higher case fatality rates. Effective prophylactic and therapeutic interventions to counter this deadly virus are suggested. Conclusion: In the face of the lack of effective therapeutics and preventives against MVD, supportive care is the only available option which contributes to the growing concern and disease severity. In view of the preventive approaches involving effective surveillance and monitoring system following the "One Health" model is extremely beneficial to ensure a healthy world for all, this article aims at emphasizing several MVD outbreaks, epidemiology, zoonosis of the virus, current treatment strategies, risk assessments, and the mitigation strategies against MVD.

Modeling of chitosan modified PLGA atorvastatin-curcumin conjugate (AT-CU) nanoparticles, overcoming the barriers associated with PLGA: An approach for better management of atherosclerosis.

Conjugate drugs are evolving into potent techniques in the drug development process for enhancing the biopharmaceutical, physicochemical, and pharmacokinetic properties. Atorvastatin (AT) is the first line of treatment for coronary atherosclerosis; however its therapeutic efficacy is limited because of its poor solubility and fast pass metabolism. Curcumin (CU) is evidenced in several crucial signaling pathways linked to lipid regulation and inflammation. To enhance the therapeutic efficacy and physical properties of AT and CU, a new conjugate derivative (AT-CU) was synthesized and assessed by in silico, in vitro characterizations, and in vivo efficacy through mice model. Although the biocompatibility and biodegradability of Polylactic-co-Glycolic Acid (PLGA) in nanoparticles are well documented, burst release is a common issue with this polymer. Hence the current work used chitosan as a drug release modifier to the PLGA nanoparticles. The chitosan-modified PLGA AT-CU nanoparticles were prepaid by single emulsion and solvent evaporation technique. With raising the concentration of chitosan the particle size grew from 139.2 nm to 197.7 nm, the zeta potential rose from -20.57 mV to 28.32 mV, and the drug encapsulation efficiency improved from 71.81% to 90.57%. At 18 h, the burst release of AT-CU from PLGA nanoparticles was seen, hitting abruptly 70.8%. For chitosan-modified PLGA nanoparticles, the burst release pattern was significantly reduced which could be due to the adsorption of the drug on the surface of chitosan. The efficiency of the ideal formulation i.e F4 (chitosan/PLGA = 0.4) in treating atherosclerosis was further strongly evidenced by in vivo investigation.

Automatic Detection of Oral Squamous Cell Carcinoma from Histopathological Images of Oral Mucosa Using Deep Convolutional Neural Network.

Worldwide, oral cancer is the sixth most common type of cancer. India is in 2nd position, with the highest number of oral cancer patients. To the population of oral cancer patients, India contributes to almost one-third of the total count. Among several types of oral cancer, the most common and dominant one is oral squamous cell carcinoma (OSCC). The major reason for oral cancer is tobacco consumption, excessive alcohol consumption, unhygienic mouth condition, betel quid eating, viral infection (namely human papillomavirus), etc. The early detection of oral cancer type OSCC, in its preliminary stage, gives more chances for better treatment and proper therapy. In this paper, author proposes a convolutional neural network model, for the automatic and early detection of OSCC, and for experimental purposes, histopathological oral cancer images are considered. The proposed model is compared and analyzed with state-of-the-art deep learning models like VGG16, VGG19, Alexnet, ResNet50, ResNet101, Mobile Net and Inception Net. The proposed model achieved a cross-validation accuracy of 97.82%, which indicates the suitability of the proposed approach for the automatic classification of oral cancer data.

Celecoxib Crystallized from Hydrophilic Polymeric Solutions Showed Modified Crystalline Behavior with an Improved Dissolution Profile.

The crystallization technique has been established as a cost-effective and simple approach to improve the dissolution rate and oral bioavailability of poorly soluble drugs. This study was carried out to study the effect of some selected hydrophilic polymers such as methyl cellulose, hydroxypropyl methylcellulose (HPMC), polyvinyl alcohol, and carboxymethyl cellulose on the crystal behavior and dissolution properties of celecoxib (CLX), a common nonsteroidal anti-inflammatory drug. Structural and spectral characteristics of crystallized CLX have been studied by Fourier transform infrared (FTIR) spectroscopy, diffraction scanning calorimetry (DSC), and X-ray diffraction (XRD) analysis. From FTIR and DSC analysis, no significant shifting of peaks or appearance of any new peaks (for polymers) were observed, which indicated the absence of any major interaction between drug and polymers as well as the absence of polymers in the final crystallized product of CLX. The XRD analysis showed a change in crystalline morphology to some extent. The dissolution rate of crystallized CLX in the presence of polymers (particularly with HPMC) was significantly improved compared with plain CLX. The improved dissolution profile of the experimental CLX crystal products could be an indication of improved bioavailability of CLX for better clinical outcome.