Current Pharmaceutical Design - Volume 30, Issue 23, 2024

Gene editing technology, particularly Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) has transformed medical research. As a newly developed genome editing technique, CRISPR technology has strongly assisted scientists in enriching their comprehension of the roles of individual genes and their influences on a vast spectrum of human malignancies. Despite considerable progress in elucidating obesity's molecular pathways, current anti-obesity medications fall short in effectiveness. A thorough understanding of the genetic foundations underlying various neurobiological pathways related to obesity, as well as the neuro-molecular mechanisms involved, is crucial for developing effective obesity treatments. Utilizing CRISPR-based technologies enables precise determination of the roles of genes that encode transcription factors or enzymes involved in processes, such as lipogenesis, lipolysis, glucose metabolism, and lipid storage within adipose tissue. This innovative approach allows for the targeted suppression or activation of genes regulating obesity, potentially leading to effective weight management strategies. In this review, we have provided a detailed overview of obesity's molecular genetics, the fundamentals of CRISPR/Cas9 technology, and how this technology contributes to the discovery and therapeutic targeting of new genes associated with obesity.

The circadian clock consists of a hierarchical multi-oscillator network of intracellular and intercellular mechanisms throughout the body that contributes to anticipating metabolic activity and maintaining system homeostasis in response to environmental cues and intrinsic stimuli. Over the past few years, genetic variations of core clock genes have been associated with cancer risk in several epidemiological studies. A growing number of epidemiological research studies have demonstrated a direct correlation between the disturbance of circadian rhythms and the growth of tumors, indicating that shift workers are more susceptible to malignancies of the colon, prostate, ovarian, breast, lung, and liver. One of the most related cancers with circadian rhythm is Gastrointestinal (GI) cancer, which is a leading cause of cancer-related mortality nowadays. The aim of this review was to demonstrate the effect of the clock gene network on the growth of GI cancer, providing molecular targets for GI cancer treatment, possible prognostic biomarkers, and guidance for treatment choices.

In the last decade, there has been increasing evidence connecting mitochondrial dysfunction to the onset and advancement of atherosclerosis. Both reactive oxygen species (ROS) and the disruption of mitochondrial calcium (Ca²⁺) regulation have garnered significant attention due to their involvement in various stages of atherosclerosis. This abstract discusses the potential therapeutic applications of targeting mitochondrial calcium (Ca²⁺) and reactive oxygen species (ROS), while also providing an overview of their respective roles in atherosclerosis. The abstract underscores the importance of mitochondrial Ca²⁺ homeostasis in cellular physiology, including functions such as energy production, cell death signaling, and maintaining redox balance. Alterations in the mitochondria's Ca²⁺ handling disrupt all these procedures and speed up the development of atherosclerosis. Reactive oxygen species (ROS), generated during mitochondrial respiration, are widely recognized as significant contributors to the development of atherosclerosis. Through modulating the function of calcium ion (Ca²⁺) transport proteins, ROS can impact the regulation of mitochondrial Ca²⁺ handling. These oxidative modifications lead to vascular remodeling and plaque formation by impairing endothelial function, encouraging the recruitment of inflammatory cells, and promoting smooth muscle cell proliferation. Preclinical investigations indicate that interventions aimed at regulating the production and elimination of reactive oxygen species (ROS) hold promise for mitigating atherosclerosis. Targeting mitochondrial processes represents a prospective therapeutic strategy for addressing this condition. Further research is necessary to elucidate the intricate molecular mechanisms associated with mitochondrial dysfunction in atherosclerosis and develop effective therapeutic strategies to decelerate disease progression.

Approximately 16.5% of the United States population met the diagnostic criteria for substance use disorder (SUD) in 2021, including 29.5 million individuals with alcohol use disorder (AUD). Individuals with AUD are at increased risk for malnutrition, and impairments in nutritional status in chronic alcohol users can be detrimental to physical and emotional well-being. Furthermore, these nutritional deficiencies could contribute to the never-ending cycle of alcoholism and related pathologies, thereby jeopardizing the prospects of recovery and treatment outcomes. Improving nutritional status in AUD patients may not only compensate for general malnutrition but could also reduce adverse symptoms during recovery, thereby promoting abstinence and successful treatment of AUD. In this review, we briefly summarize alterations in the nutritional status of people with addictive disorders, in addition to the underlying neurobiological mechanisms and clinical implications regarding the role of nutritional intervention in recovery from alcohol use disorder.

Cancer remains a leading cause of death worldwide, and current cancer drugs often have high costs and undesirable side effects. Additionally, the development of drug resistance can reduce their effectiveness over time. Natural products have gained attention as potential sources for the treatment and prevention of various diseases. Curcumin, an extract from turmeric (Curcuma longa), is a natural phenolic compound with diverse pharmacological properties, including antioxidant, anti-inflammatory, antiviral, antibacterial, antifungal, antiprotozoal, antidiabetic, antivenom, antiulcer, anticarcinogenic, antimutagenic, anticoagulant, and antifertility activities. Given the increasing interest in curcumin for cancer prevention, this review aims to comprehensively examine clinical trials investigating the use of curcumin in different types of cancer. Additionally, effective techniques and approaches to enhance the bioavailability of curcumin are discussed and summarized. This review article provides insights into the properties of curcumin and its potential as a future anticancer drug.

Introduction: This study focuses on the development of novel antimicrobial agents. A Schiff base ligand, 6-(2-(4-hydroxy-3-methoxybenzylideneamino)-2-(4-hydroxyphenyl)acetamido)-3,3-dimethyl-7-oxo- 4-thia-1-azabicyclo [3.2.0] heptane-2-carboxylic acid, synthesized through the condensation of amoxicillin and vanillin in methanol, served as the foundation. Polydentate mixed ligand complexes were then formed by reacting the Schiff base with metal ions (Fe(II), Co(II), Ni(II), Cu(II), and Zn(II)) and nicotinamide in specific ratios. Methods: Characterization involved various techniques, such as ¹H-NMR, FT-IR, UV-Vis, and elemental analysis for the ligand, and Atomic Absorption, FT-IR, UV-Vis, magnetic susceptibility, and conductance measurements for the Schiff base-metal ion complexes. Results: Quantum chemical features of both ligands and metal complexes were computed, refining their electronic and molecular structures theoretically. Antimicrobial activity against Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, Salmonella typhi, Acinetobacter baumannii, and Pseudomonas aeruginosa was assessed for the starting materials, ligands, and synthesized complexes, revealing significant effects on certain species. In-silico binding modes with Escherichia coli (PDB ID: 5iq9) were determined through molecular docking. Conclusion: This study underscores the potential applications of the Schiff base ligands and their metal complexes in developing new antimicrobial agents.