Anthropometric, clinical and biochemical characteristics in non NAFLD and NAFLD groups of both genders.

<p>Results are expressed as number (percentage), mean ± SD; n = number of subjects; SGPT, serum glutamate pyruvate transaminase; GGT, gama glutamate transaminase; SGOT, serum glutamate oxaloacetate transaminase; HOMA%B, β cell function assessed by homeostasis model assessment; HOMA%S: insulin sensitivity assessed by homeostasis model assessment; HOMA-IR, insulin resistance assessed by homeostasis model assessment; NAFLD, nonalcoholic fatty liver disease.</p><p>Anthropometric, clinical and biochemical characteristics in non NAFLD and NAFLD groups of both genders.</p

General characteristic of the study subjects by gender.

<p>Results are expressed as number (percentage), mean ± SD; n = number of subjects; HOMA%B, β cell function assessed by homeostasis model assessment; HOMA%S, insulin sensitivity assessed by homeostasis model assessment; HOMA-IR, insulin resistance assessed by homeostasis model assessment; NAFLD, nonalcoholic fatty liver disease.</p><p>General characteristic of the study subjects by gender.</p

Circulating leptin levels in the study subjects.

<p>Log transformed serum leptin was significantly higher in female subjects compared to their male counterparts (<i>P</i> = 0.001).</p

Structure-Based Discovery of Novel Cyclophilin A Inhibitors for the Treatment of Hepatitis C Virus Infections

Hepatitis C virus (HCV) is a major cause of end-stage liver disease. Direct-acting antivirals (DAAs), including inhibitors of nonstructural proteins (NS3/4A protease, NS5A, and NS5B polymerase), represent key components of anti-HCV treatment, but these are associated with increased drug resistance and toxicity. Thus, the development of host-targeted antiviral agents, such as cyclophilin A inhibitors, is an alternative approach for more effective, selective, and safer treatment. Starting with the discovery of a bis-amide derivative <b>5</b> through virtual screening, the lead compound <b>25</b> was developed using molecular modeling-based design and systematic exploration of the structure–activity relationship. The lead <b>25</b> lacked cytotoxicity, had potent anti-HCV activity, and showed selective and high binding affinity for CypA. Unlike cyclosporin A, <b>25</b> lacked immunosuppressive effects, successfully inhibited the HCV replication, restored host immune responses without acute toxicity in vitro and in vivo, and exhibited a high synergistic effect in combination with other drugs. These findings suggest that the bis-amides have significant potential to extend the arsenal of HCV therapeutics

Structure-Based Discovery of Novel Cyclophilin A Inhibitors for the Treatment of Hepatitis C Virus Infections

Hepatitis C virus (HCV) is a major cause of end-stage liver disease. Direct-acting antivirals (DAAs), including inhibitors of nonstructural proteins (NS3/4A protease, NS5A, and NS5B polymerase), represent key components of anti-HCV treatment, but these are associated with increased drug resistance and toxicity. Thus, the development of host-targeted antiviral agents, such as cyclophilin A inhibitors, is an alternative approach for more effective, selective, and safer treatment. Starting with the discovery of a bis-amide derivative <b>5</b> through virtual screening, the lead compound <b>25</b> was developed using molecular modeling-based design and systematic exploration of the structure–activity relationship. The lead <b>25</b> lacked cytotoxicity, had potent anti-HCV activity, and showed selective and high binding affinity for CypA. Unlike cyclosporin A, <b>25</b> lacked immunosuppressive effects, successfully inhibited the HCV replication, restored host immune responses without acute toxicity in vitro and in vivo, and exhibited a high synergistic effect in combination with other drugs. These findings suggest that the bis-amides have significant potential to extend the arsenal of HCV therapeutics