No abstract

Hsp90 is a ubiquitous chaperone with important roles in the organization and maturation of client proteins that are involved in the progression and survival of cancer cells. Multiple oncogenic pathways can be affected by inhibition of Hsp90 function through degradation of its client proteins. That makes Hsp90 a therapeutic target for cancer treatment. 17‐allylamino‐17‐demethoxy‐geldanamycin (17‐AAG) is a potent Hsp90 inhibitor that binds to Hsp90 and inhibits its chaperoning function, which results in the degradation of Hsp90's client proteins. There have been several preclinical studies of 17‐AAG as a single agent or in combination with other anticancer agents for a wide range of human cancers. Data from various phases of clinical trials show that 17‐AAG can be given safely at biologically active dosages with mild toxicity. Even though 17‐AAG has suitable pharmacological potency, its low water solubility and high hepatotoxicity could significantly restrict its clinical use. Nanomaterials‐based drug delivery carriers may overcome these drawbacks. In this paper, we review preclinical and clinical research on 17‐AAG as a single agent and in combination with other anticancer agents. In addition, we highlight the potential of using nanocarriers and nanocombination therapy to improve therapeutic effects of 17‐AAG.

Activation of caspase, externalization of phosphatidyl serine, change in the mitochondrial membrane potential, and DNA fragmentation are apoptosis markers found in human ejaculated spermatozoa. Also, reactive oxygen species (ROS) play a vital role in the different types of male infertility. In this review, data sources including Google Scholar, Scopus, PubMed, and Science Direct were searched for publications with no particular time restriction to get a holistic and comprehensive view of the research. Apoptosis regulates the male germ cells, correct function and development from the early embryonic stages of gonadal differentiation to fertilization. In addition to maintaining a reasonable ratio between the Sertoli and germ cells, apoptosis is one of the well-known quality control mechanisms in the testis. Also, high ROS levels cause a heightened and dysregulated apoptotic response. Apoptosis is one of the well-known mechanisms of quality control in the testis. Nevertheless, increased apoptosis may have adverse effects on sperm production. Recent studies have shown that ROS and the consequent oxidative stress play a crucial role in apoptosis. This review aims to assimilate and summarize recent findings on the apoptosis in male reproduction and fertility. Also, this review discusses the update on the role of ROS in normal sperm function to guide future research in this area. Key words: Fertility, Spermatogonia, Apoptosis, Reproduction, DNA fragmentation, DNA integrity, ROS.

Background/Aims: The C1431T polymorphism of peroxisome proliferator activated receptor-γ (PPAR-γ) gene is related to diabetes and metabolic-syndrome. However, studies have been inconclusive about its association with coronary artery disease (CAD) and there have been no studies analyzing the association of this polymorphism with fasted-serum-lipid levels in Iranian-individuals with CAD. We investigated the association of PPAR-γ C1431T-polymorphism with CAD and dyslipidaemia in 787 individuals. Methods: Anthropometric-parameters and biochemical-measurements were evaluated, followed by genotyping. The association of the genetic-polymorphisms with CAD and lipid-profile was determined by univariate/multivariate-analyses. Results: Patients with CT or CT+TT genotype were at an increased-risk of CAD relative to CC-carriers (adjusted odds ratio: 2.03; 95% confidence interval, 1.01-4.09; p = 0.046). However, in the larger population, CT genotype was present at a higher frequency in the group with a positive angiogram. Furthermore, CT+TT genotypes were associated with an altered fasted-lipid-profile in the initial population sample of patients with a positive angiogram, compared to the group with a negative-angiogram. The angiogram-positive patients carrying the T allele had a significantly higher triglyceride, serum C-reactive protein and fasting-blood-glucose. Conclusion: We have found the PPAR-γ C1431T polymorphism was significantly associated with fasted serum lipid profile in individuals with angiographically defined CAD. Since accumulating data support the role of PPAR-γ polymorphisms in CAD, further studies are required to investigate the association of this polymorphism with coronary artery disease.

No abstract