Curcumin and cancer: An “old-age” disease with an “age-old” solution

m6A Modification in Coding and Non-coding RNAs: Roles and Therapeutic Implications in Cancer

Male infertility accounts for up to half of the infertility cases and affects 13–15% couples worldwide. An optimal level of reactive oxygen species is crucial for maintaining spermatogenesis and sperm functions. However, excessive production of reactive oxygen species may cause oxidative stress. Oxidative stress has been identified as one of the major risk factors which affects the fertilizing potential of spermatozoa. Oxidative stress occurs due to excessive production of ROS and causes germ cell DNA damage, sperm fragility and defects in motility, culminating in infertility. Poor sperm quality and DNA damage may also result in pregnancy loss. This article highlights the significance of ROS in human male fertility and that of oxidative stress in infertility.

Oxidative stress and male infertility

Male infertility is a multifactorial pathological condition affecting approximately 7% of the male population. The genetic landscape of male infertility is highly complex as semen and testis histological phenotypes are extremely heterogeneous, and at least 2,000 genes are involved in spermatogenesis. The highest frequency of known genetic factors contributing to male infertility (25%) is in azoospermia, but the number of identified genetic anomalies in other semen and aetiological categories is constantly growing. Genetic screening is relevant for its diagnostic value, clinical decision making, and appropriate genetic counselling. Anomalies in sex chromosomes have major roles in severe spermatogenic impairment. Autosome-linked gene mutations are mainly involved in central hypogonadism, monomorphic teratozoospermia or asthenozoospermia, congenital obstructive azoospermia, and familial cases of quantitative spermatogenic disturbances. Results from whole-genome association studies suggest a marginal role for common variants as causative factors; however, some of these variants can be important for pharmacogenetic purposes. Results of studies on copy number variations (CNVs) demonstrate a considerably higher CNV load in infertile patients than in normozoospermic men, whereas whole-exome analysis has proved to be a highly successful diagnostic tool in familial cases of male infertility. Despite such efforts, the aetiology of infertility remains unknown in about 40% of patients, and the discovery of novel genetic factors in idiopathic infertility is a major challenge for the field of androgenetics. Large, international, and consortium-based whole-exome and whole-genome studies are the most promising approach for the discovery of the missing genetic aetiology of idiopathic male infertility.

Genetics of male infertility.

N6-methyladenosine (m6A) is considered the most common, abundant, and conserved internal transcript modification, especially in eukaryotic messenger RNA (mRNA). m6A is installed by m6A methyltransferases (METTL3/14, WTAP, RBM15/15B, VIRMA and ZC3H13, termed “writers”), removed by demethylases (FTO, ALKBH5, and ALKBH3, termed “erasers”), and recognized by m6A-binding proteins (YTHDC1/2, YTHDF1/2/3, IGF2BP1/2/3, HNRNP, and eIF3, termed “readers”). Accumulating evidence suggests that m6A RNA methylation greatly impacts RNA metabolism and is involved in the pathogenesis of many kinds of diseases, including cancers. In this review, we focus on the physiological functions of m6A modification and its related regulators, as well as on the potential biological roles of these elements in human tumors.

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The potential role of RNA N6-methyladenosine in Cancer progression

METTL14 Suppresses CRC Progression via Regulating N6-Methyladenosine-Dependent Primary miR-375 Processing.

Behavioral, neurochemical and neuroendocrine effects of the ethanolic extract from Curcuma longa L. in the mouse forced swimming test.

Behavioral and biochemical studies of total furocoumarins from seeds of Psoralea corylifolia in the chronic mild stress model of depression in mice.

Health benefits of isoflavones such as genistein and daidzein have led to an increasing interest in consuming soybeans or soy-containing food. However, possible adverse effects of such plant estrogens on the male reproductive system, particularly penile erection, have not been sufficiently evaluated. In previous research, we observed that exposure of adult rats to daidzein could attenuate apomorphine-induced erections. To identify the impact of daidzein exposure in early life on erectile function, we evaluated erectile capacity using an apomorphine-induced erectile test and determining intracavernous pressure after exposure of juvenile rats to daidzein at a dose of 2, 20, or 100 mg/kg for 90 days. Meanwhile, the levels of sex hormones, including testosterone, luteinizing hormone, and follicle-stimulating hormone, were determined. Both subtypes of the estrogen receptor (α and β) in the corpora cavernosa were also detected immunohistochemically. When the rats were examined at adulthood, we observed that those animals treated with a medium (20 mg/kg) or high (100 mg/kg) dose of daidzein, but not with a low dose (2 mg/kg), showed lower plasma testosterone levels and attenuated erectile parameters, including apomorphine-induced erections and intracavernous pressure concomitant with markedly decreased expression of estrogen receptor β in the corpora cavernosa. However, the penis still grew to its normal size, as in controls. Thus, these results suggested that exposure of juvenile rats to daidzein in a relatively large amount could adversely affect penile erection in adulthood.

https://onlinelibrary.wiley.com/doi/pdf/10.2164/jandrol.107.003392

Exposure of Juvenile Rats to the Phytoestrogen Daidzein Impairs Erectile Function in a Dose‐Related Manner in Adulthood

Type 2 diabetes mellitus (T2-DM) is a chronic metabolic disorder characterized by high blood glucose levels. T2-DM patients suffer from many complications, such as diabetic fatty liver and diabetic nephropathy. The liver, the pivotal organ involved in both glucose and lipid metabolism, is primarily damaged in T2-DM patients, especially in those with high levels of blood lipid. In this study, the hepatoprotective activity of ginsenoside Rg1 was investigated in a T2-DM rat model. The results revealed a potent hepatoprotective effect of ginsenoside Rg1. This effect was primarily mediated by the antiapoptotic effect, inhibition of JNK activity, and suppression of inflammation after ginsenoside Rg1 treatment. Ginsenoside Rg1 also lowered the blood glucose level and insulin resistance index in T2-DM rats. Moreover, the blood lipid profile (total cholesterol, triglycerides, and low-density lipoprotein cholesterol levels) and liver function (aspartate transaminase and alanine transaminase levels) improved after ginsenoside Rg1 treatment. The aforementioned hepatoprotective effects of ginsenoside Rg1 in the T2-DM rat model suggests its clinical potential as an adjuvant drug for T2-DM therapy, especially for T2-DM patients with fatty liver disease.

/pdf/effects-of-ginsenoside-rg1-on-glucose-metabolism-and-liver-4614dl2pq8.pdf

Xin-Yi Xia

Papers

METTL14 Suppresses CRC Progression via Regulating N6-Methyladenosine-Dependent Primary miR-375 Processing.

Behavioral, neurochemical and neuroendocrine effects of the ethanolic extract from Curcuma longa L. in the mouse forced swimming test.

Behavioral and biochemical studies of total furocoumarins from seeds of Psoralea corylifolia in the chronic mild stress model of depression in mice.

Exposure of Juvenile Rats to the Phytoestrogen Daidzein Impairs Erectile Function in a Dose‐Related Manner in Adulthood

Effects of ginsenoside Rg1 on glucose metabolism and liver injury in streptozotocin-induced type 2 diabetic rats.