Impact of ACE2 genetic variant on antidepressant efficacy of SSRIs.

Identification of a new axis of angiotensin-converting enzyme 2 (ACE2)/angiotensin (1-7)/Mas receptor, in the renin-angiotensin system (RAS), has opened a new insight regarding the role of RAS and angiotensin in higher brain functions. ACE2 catabolizes angiotensin II and produces angiotensin (1-7), an agonist of Mas receptor. Mice lacking the Mas receptor (angiotensin 1-7 receptor) exhibit anxiety-like behaviours. The present study was conducted to test the hypothesis of the involvement of ACE2 genetic variant (G8790A) on response to selective serotonin reuptake inhibitors (SSRIs). In a randomised control trial, 200 newly diagnosed Iranian patients with major depressive disorder completed 6 weeks of fluoxetine or sertraline treatment. Patients with a reduction of 50% or more in the Hamilton Rating Scale for Depression score were considered responsive to treatment. G8790A polymorphism was determined in extracted DNAs using restriction fragment length polymerase chain reaction method. Our results show that the A allele and AA and GA genotypes were significantly associated with better response to SSRIs (p = 0.008; OR = 3.4; 95% CI = 1.4-8.5 and p = 0.027; OR = 3.3, 95% CI = 1.2-9.2, respectively). Moreover, patients with GA and AA genotypes responded significantly better to sertraline (p = 0.0002; OR = 9.1; 95% CI = 2.4-33.7). The A allele was significantly associated with better response to sertraline (p = 0.0001; OR = 7.6; 95% CI = 2.5-23.3). In conclusion, our results confirm the role of G8790A in response to some SSRIs.

Therapeutic applications of herbal/synthetic/bio-drug in oral cancer: An update.

Oral cancer, as one of the most prevalent and invasive cancers that invade local tissue, can cause metastasis, and have high mortality. In 2018, around 355,000 worldwide oral cancers occurred and resulted in 177,000 deaths. Estimates for the year 2020 include about 53,260 new cases added to previous year's cases, and the estimated death toll from this cancer in 2020 is about 10,750 deaths more than previous years. Despite recent advances in cancer diagnosis and treatment, unfortunately, 50% of people with cancer cannot be cured. Of course, it should be remembered that the type of treatment used greatly influences patient recovery. There are not many choices when it comes to treating oral cancer. Research efforts focusing on the discovery and evolution of innovative therapeutic approaches for oral cancer are essential. Such traditional methods of treating this type of cancer like surgery and chemotherapy, have evolved dramatically during the past thirty to forty years, but they continue to cause panic among patients due to their side effects. Therefore, it is necessary to study and use drugs that are less risky for the patient as well as to provide solutions to reduce chemotherapy-induced adverse events that prevent many therapeutic risks. As mentioned above, this study examines low-risk therapies such as herbal remedies, biological drugs, and synthetic drugs in the hope that they will be useful to physicians, researchers, and scientists around the world.

Overexpression of Adiponectin Receptors in Opium Users with and without Cancer.

AIM: Opium addiction is a serious public health concern in the Middle East countries causing various illnesses. Opium use is associated with an increased risk of several cancers; however, the underlying mechanisms are not yet fully elucidated. Altered levels of adiponectin and its related main receptors, Adiponectin receptor 1 and 2 (AdipoR1 and AdipoR2) have been associated with several malignancies. Opium users are at risk of various cancers. All together let us to the hypothesis that probable overexpression of AdipoRs in opium users might be linked to the occurrence of cancer in this population. METHODS: One hundred opium users along with 100 healthy non-opium users were enrolled in the study. Opium users were followed up for 5 years (2014-2019) to evaluate the occurrence of malignancies. AdipoR1 and AdipoR2 expressions were measured using a flow cytometry method. RESULTS: Expression of AdipoR1 and AdipoR2 was significantly higher in opium users compared with the healthy control group (P=0.0001 and 0.0001, respectively). Eight opium users developed cancer during the follow-up period. Subjects abusing opium developed cancer by 8.6 folds comparing to non-opium users (P=0.034; OR=8.6; 95% CI (1.06-70.1)). Expression of these two receptors was significantly higher in opium users developing cancer compared with cancer-free opium (P=0.001). CONCLUSION: Considering the significant overexpression of AdipoR1 and AdipoR2 in opium users and in opium users who developed malignancies and the association between upregulation of these receptors in most cancers affecting opium users and assessment of AdipoRs may serve as an early detection tool of cancer in this population.

Orexin/Hypocretin Type 2 Receptor (HCRTR2) Gene as a Candidate Gene in Sertraline-Associated Insomnia in Depressed Patients.

BACKGROUND: Selective serotonin reuptake inhibitors (SSRIs) are considered as first-line drugs for treating depressive disorders. Among the adverse effects reported with sertraline is sleep disturbances; however, the etiology lying beneath is obscure. Orexin, the most recently discovered neurotransmitter, is involved in the sleep cycle. It exerts its physiological actions through orexin or hypocretin type 1 and 2 receptors (HCRTR1 and HCRTR2). Dysfunction of the orexin system contributes to various psychiatric, neurologic and neuropsychiatric disorders. Thus, our study aimed to assess the possible association of genetic variation of HCRTR2 G1246A with hypersomnia reported with sertraline in a group of major depressive disorder (MDD) patients. PATIENTS AND METHODS: Ninety-six newly diagnosed MDD patients were enrolled in our cohort study. MDD was assessed using DSM-V criteria. Insomnia Severity Index (ISI) was used to assess insomnia at baseline (week 0) and week 4. Blood samples were collected for further genotyping of HCRTR2 G1246A (rs2653349) using polymerase chain reaction-restriction fragment length polymorphism. RESULTS: A significant association between G1264A polymorphism of HCRTR2 and insomnia was observed. Insomnia with sertraline happens by 2.5-fold (P=0.022; odds ratio (OR)=2.5; 95% confidence interval (CI): 1.1-5.7) in patients having GG genotype. Patients with G allele experience insomnia by 2.1-fold more than A allele carriers (P=0.022; OR=2.1; 95% CI= 1.1-4.0). Subgroup analysis showed a significant association between GG genotype as well as the G allele and insomnia only in female MDD patients (P=0.011; OR=4.0; 95% CI=1.3-12.0 and P=0.033; OR=2.4; 95% CI=1.02-5.7, respectively). CONCLUSION: In conclusion, the G1246A variant might be a predictor for insomnia in MDD patients treated with sertraline. Our findings support the idea that some variants of the HCRTR might contribute to inter-individual variability in the sleep pattern of patients receiving antidepressants.

Cholestasis-associated reproductive toxicity in male and female rats: The fundamental role of mitochondrial impairment and oxidative stress.

Cholestasis is a significant decrease in bile flow. The liver is the primary organ affected by cholestasis. Chronic cholestasis could entail to tissue fibrotic changes and liver cirrhosis. Other organs, including heart, kidneys, nervous system, skeletal muscles, as well as the reproductive system, might also be affected during cholestasis. Although the cholestasis-associated pathological and biochemical alterations in organs such as liver have been widely investigated, there is little information about complications such as cholestasis-induced reproductive toxicity. The current study aimed to evaluate the pathologic effects of cholestasis on reproductive organs in both male and female animals. Rats underwent bile duct ligation (BDL) surgery. Markers of reproductive toxicity, including serum hormonal changes, tissue histopathological alterations, biomarkers of oxidative stress, and markers of mitochondrial impairment, were evaluated. Increased serum markers of liver injury and elevated level of cytotoxic molecules such as bile acids and bilirubin were evident in BDL animals. On the other hand, the serum level of hormones such as testosterone was suppressed in BDL rats. Significant histopathological alterations were also evident in the testis and ovary of BDL animals. A significant increase in oxidative stress markers, including ROS formation, lipid peroxidation, protein carbonylation, and depleted glutathione and antioxidant reservoirs were also detected in BDL rats. Moreover, mitochondrial depolarization decreased dehydrogenases activity, and depleted ATP content was detected in sperm isolated from the BDL group. These data indicate that cholestasis-associated reproductive toxicity in male and female rats is restrictedly coupled with severe oxidative stress and mitochondrial impairment.