A comprehensive review on role of Aurora kinase inhibitors (AKIs) in cancer therapeutics.

Aurora kinases (AURKs) are a family of serine /threonine protein kinases that have a crucial role in cell cycle process mainly in the event of chromosomal segregation, centrosome maturation and cytokinesis. The family consists of three members including Aurora kinase A (AURK-A), Aurora kinase B (AURK-B) and Aurora kinase C (AURK-C). All AURKs contain a conserved kinase domain for their activity but differ in their cellular localization and functions. AURK-A and AURK-B are expressed mainly in somatic cells while the expression of AURK-C is limited to germ cells. AURK-A promotes G2 to M transition of cell cycle by controlling centrosome maturation and mitotic spindle assembly. AURK-B and AURK-C form the chromosome passenger complex (CPC) that ensures proper chromosomal alignments and segregation. Aberrant expression of AURK-A and AURK-B has been detected in several solid tumours and malignancies. Hence, they have become an attractive therapeutic target against cancer. The first part of this review focuses on AURKs structure, functions, subcellular localization, and their role in tumorigenesis. The review also highlights the functional and clinical impact of selective as well as pan kinase inhibitors. Currently, >60 compounds that target AURKs are in preclinical and clinical studies. The drawbacks of existing inhibitors like selectivity, drug resistance and toxicity have also been addressed. Since, majority of inhibitors are Aurora kinase inhibitor (AKI) type-1 that bind to the active (DFGin and Cin) conformation of the kinase, this information may be utilized to design highly selective kinase inhibitors that can be combined with other therapeutic agents for better clinical outcomes.

Insights into the preventive actions of natural compounds against Klebsiella pneumoniae infections and drug resistance.

Klebsiella pneumoniae is a type of Gram-negative bacteria that causes a variety of infections, including pneumonia, bloodstream infections, wound infections, and meningitis. The treatment of K. pneumoniae infection depends on the type of infection and the severity of the symptoms. Antibiotics are generally used to treat K. pneumoniae infections. However, some strains of K. pneumoniae have become resistant to antibiotics. This comprehensive review examines the potential of natural compounds as effective strategies against K. pneumonia infections. The alarming rise in antibiotic resistance underscores the urgent need for alternative therapies. This article represents current research on the effects of diverse natural compounds, highlighting their anti-microbial and antibiofilm properties against K. pneumonia. Notably, compounds such as andrographolide, artemisinin, baicalin, berberine, curcumin, epigallocatechin gallate, eugenol, mangiferin, piperine, quercetin, resveratrol, and thymol have been extensively investigated. These compounds exhibit multifaceted mechanisms, including disruption of bacterial biofilms, interference with virulence factors, and augmentation of antibiotic effectiveness. Mechanistic insights into their actions include membrane perturbation, oxidative stress induction, and altered gene expression. While promising, challenges such as limited bioavailability and varied efficacy across bacterial strains are addressed. This review further discusses the potential of natural compounds as better alternatives in combating K. pneumonia infection and emphasizes the need for continued research to harness their full therapeutic potential. As antibiotic resistance persists, these natural compounds offer a promising avenue in the fight against K. pneumonia and other multidrug-resistant pathogens.

Effects of combined whole body vibration and resistance training on lower quadrants electromyographic activity, muscle strength and power in athletes.

BACKGROUND: Whole body vibration (WBV) with resistance training is one of the increasing ways of gaining ankle and foot complex muscle strength and power for the rehabilitative and prophylactic purpose in athletes. OBJECTIVE: The purpose of the study was to compare the effects of combined WBV and resistance training (RVE) with strength training alone (RE) on alteration of gastrocnemius lateralis and vastus medialis obliquus muscle activity and strength, and power performance in athletes. METHODS: The study was performed on 23 university-level male athletes who were randomized into two groups as RVE (n = 12; age 22.2 ± 1.94 years) and RE (n = 11; age 21.60 ± 1.78 years). The training program was scheduled three times per week for six weeks (18 sessions). Gastrocnemius lateralis (GL) and vastus medialis obliquus (VMO) were measured for muscle activity and isometric strength with surface EMG device and handheld dynamometer respectively. Counter-movement jump (CMJ) was used for measuring power. All the participants were assessed for outcome measures at baseline and then after 6 weeks. Group (RVE vs. RE) by time (pre vs. post) effects were compared through a 2-way interaction utilizing mixed model repeated measure ANOVA. RESULTS: After training, VMO muscle activity (group effects) increased significantly in the RVE group (p < 0.05). However, both the groups showed statistically significant time and group × time interaction effects for muscle activity of VMO, isometric strength (VMO and GL), and CMJ (p < 0.05). CONCLUSION: WBV might serve as an adjunct modality for enhancement of the neuromuscular activity of the VMO muscle. However, RVE had no additive effect when compared to RE alone on muscle strength and power in athletes. The long-term impacts of combined WBV and resistance training on other foot and ankles muscle should be investigated in future studies.