The major products of the trichothecene mycotoxin biosynthetic pathway produced in a species- and sometimes isolate-specific manner by cereal-pathogenic Fusarium fungi include T-2 toxin, diacetoxyscirpenol, deoxynivalenol and nivalenol. This paper briefly reviews the major effects of such trichothecenes on the gross morphology, cytology and molecular signalling within eukaryotic cells. The gross toxic effects of select trichothecenes on animals include growth retardation, reduced ovarian function and reproductive disorders, immuno-compromization, feed refusal and vomiting. The phytotoxic effects of deoxynivalenol on plants can be summarized as growth retardation, inhibition of seedling and green plant regeneration. Trichothecenes are now recognized as having multiple inhibitory effects on eukaryote cells, including inhibition of protein, DNA and RNA synthesis, inhibition of mitochondrial function, effects on cell division and membrane effects. In animal cells, they induce apoptosis, a programmed cell death response. Current knowledge about the eukaryotic signal transduction cascades and downstream gene products activated by trichothecenes is limited, especially in plants. In mammalian cells, certain trichothecenes trigger a ribotoxic stress response and activate mitogen-activated protein kinases. DON mediates the inflammatory response by modulating the binding activities of specific transcription factors and subsequently inducing cytokine gene expression. Several genes are up-regulated in wheat in response to trichothecene mycotoxins; the significance, if any, of these genes in the host response to trichothecenes has yet to be elucidated.

https://www.tandfonline.com/doi/pdf/10.1080/02652030500058403

Effects of trichothecene mycotoxins on eukaryotic cells: a review.

Cancer is a frightful disease and represents one of the biggest health-care issues for the human race and demands a proactive strategy for cure. Plants are reservoirs for novel chemical entities and provide a promising line for research on cancer. Hitherto, being effective, chemotherapy is accompanied by certain unbearable side effects. Nevertheless, plants and plant derived products is a revolutionizing field as these are Simple, safer, eco-friendly, low-cost, fast, and less toxic as compared with conventional treatment methods. Phytochemicals are selective in their functions and acts specifically on tumor cells without affecting normal cells. Carcinogenesis is complex phenomena that involves many signaling cascades. Phytochemicals are considered suitable candidates for anticancer drug development due to their pleiotropic actions on target events with multiple manners. The research is in progress for developing potential candidates (those can block or slow down the growth of cancer cells without any side effects) from these phytochemicals. Many phytochemicals and their derived analogs have been identified as potential candidates for anticancer therapy. Effort has been made through this comprehensive review to highlight the recent developments and milestones achieved in cancer therapies using phytomolecules with their mechanism of action on nuclear and cellular factors. Furthermore, drugs for cancer treatment and their limitations have also been discussed.

https://cyberleninka.org/article/n/127798.pdf

Plant-derived anticancer agents: A green anticancer approach

Background Previous studies raise the possibility that antioxidants protect against neurodegenerative diseases. Objective To examine whether intake of antioxidant nutrients, including vitamin E, vitamin C, and carotene, is associated with reduced cognitive decline with age. Design Longitudinal population-based study conducted from September 17, 1993, to November 20, 2000, with an average follow-up of 3.2 years. Patients The patients were 2889 community residents, aged 65 to 102 years, who completed a food frequency questionnaire, on average 18 months after baseline. Main Outcome Measure Cognitive change as measured by 4 tests (the East Boston Memory Test, which tests immediate and delayed recall; the Mini-Mental State Examination; and the Symbol Digit Modalities Test) at baseline and 3 years for all participants, and at 6 months for 288 randomly selected participants. Results We used random-effects models to estimate nutrient effects on individual change in the average score of the 4 cognitive tests. The cognitive score declined on average by 5.0 × 10 −2 standardized units per year. There was a 36% reduction in the rate of decline among persons in the highest quintile of total vitamin E intake (−4.3 × 10 −2 standardized units per year) compared with those in the lowest quintile (−6.7 × 10 −2 standardized units per year) ( P = .05), in a model adjusted for age, race, sex, educational level, current smoking, alcohol consumption, total calorie (energy) intake, and total intakes of vitamin C, carotene, and vitamin A. We also observed a reduced decline with higher vitamin E intake from foods ( P = .03 for trend). There was little evidence of association with vitamin C or carotene intake. Conclusion Vitamin E intake, from foods or supplements, is associated with less cognitive decline with age.

https://jamanetwork.com/journals/jamaneurology/articlepdf/782440/NOC20047.pdf

Vitamin E and cognitive decline in older persons.

Importance Obsessive-compulsive disorder (OCD) is a neuropsychiatric disorder associated with significant impairment and a lifetime prevalence of 1% to 3%; however, it is often missed in primary care settings and frequently undertreated. Objective To review the most current data regarding screening, diagnosis, and treatment options for OCD. Evidence Review We searched PubMed, EMBASE, and PsycINFO to identify randomized controlled trials (RCTs), meta-analyses, and systematic reviews that addressed screening and diagnostic and treatment approaches for OCD among adults (≥18 years), published between January 1, 2011, and September 30, 2016. We subsequently searched references of retrieved articles for additional reports. Meta-analyses and systematic reviews were prioritized; case series and reports were included only for interventions for which RCTs were not available. Findings Among 792 unique articles identified, 27 (11 RCTs, 11 systematic reviews or meta-analyses, and 5 reviews/guidelines) were selected for this review. The diagnosis of OCD was revised for the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, which addresses OCD separately from anxiety disorders and contains specifiers to delineate the presence of tics and degree of insight. Treatment advances include increasing evidence to support the efficacy of online-based dissemination of cognitive behavioral therapies, which have demonstrated clinically significant decreases in OCD symptoms when conducted by trained therapists. Current evidence continues to support the use of selective serotonin reuptake inhibitors as first-line pharmacologic interventions for OCD; however, more recent data support the adjunctive use of neuroleptics, deep-brain stimulation, and neurosurgical ablation for treatment-resistant OCD. Preliminary data suggest safety of other agents (eg, riluzole, ketamine, memantine, N-acetylcysteine, lamotrigine, celecoxib, ondansetron) either in combination with selective serotonin reuptake inhibitors or as monotherapy in the treatment of OCD, although their efficacy has not yet been established. Conclusions and Relevance The dissemination of computer-based cognitive behavioral therapy and improved evidence supporting it represent a major advancement in treatment of OCD. Although cognitive behavioral therapy with or without selective serotonin reuptake inhibitors remains a preferred initial treatment strategy, increasing evidence that supports the safety and efficacy of neuroleptics and neuromodulatory approaches in treatment-resistant cases provides alternatives for patients whose condition does not respond to first-line interventions.

https://jamanetwork.com/journals/JAMA/articlepdf/2614194/jrv170001supp1_prod.pdf

Obsessive-Compulsive Disorder: Advances in Diagnosis and Treatment.

Cancer is a serious concern at present. A large number of patients die each year due to cancer illnesses in spite of several interventions available. Development of an effective and side effects lacking anticancer therapy is the trending research direction in healthcare pharmacy. Chemical entities present in plants proved to be very potential in this regard. Bioactive phytochemicals are preferential as they pretend differentially on cancer cells only, without altering normal cells. Carcinogenesis is a complex process and includes multiple signaling events. Phytochemicals are pleiotropic in their function and target these events in multiple manners; hence they are most suitable candidate for anticancer drug development. Efforts are in progress to develop lead candidates from phytochemicals those can block or retard the growth of cancer without any side effect. Several phytochemicals manifest anticancer function in vitro and in vivo. This article deals with these lead phytomolecules with their action mechanisms on nuclear and cellular factors involved in carcinogenesis. Additionally, druggability parameters and clinical development of anticancer phytomolecules have also been discussed.

/pdf/lead-phytochemicals-for-anticancer-drug-development-2tw3uui46a.pdf

Lead Phytochemicals for Anticancer Drug Development.

In Vitro Cytotoxicity of a New Epoxy Resin Root Canal Sealer

In vitro inhibitory effects of antioxidants on cytotoxicity of T-2 toxin.

Background: Ciprofloxacin is a commonly prescribed antibiotic in the treatment of genitourinary tract infection. Objective: The aim of this study was to investigate the effects of ciprofloxacin on testis apoptosis and sperm parameters in rat. Materials and Methods: Twenty male Wistar rats were selected and randomly divided into two groups; control (n=10) and experimental (n=10). The experimental group was orally received 12.5 mg/kg ciprofloxacin daily for 60 days and the control group just received water and food. Rats were then killed and sperm removed from cauda epididymis and analyzed for sperm motility, morphology, and viability. Testis tissues were also removed and prepared for TUNEL assay to detect apoptosis. Results: Results showed that ciprofloxacin significantly decreased the sperm concentration, motility (pl0.05) and viability (pl0.001). In addition, ciprofloxacin treatment resulted in a significant decrease in the number of spermatogenic cells (spermatogonia, spermatocyte, spermatid and sperm) in the seminiferous tubules when compared with the control group. The apoptotic germ cells per seminiferous tubular cross section was significantly increased in the experimental group (15.11±3.523) as compared with the control group (7.3±0.762) (pl0.05). Conclusion: It is concluded that ciprofloxacin has the toxicological effects on reproductive system in male rats.

/pdf/adverse-effects-of-ciprofloxacin-on-testis-apoptosis-and-4le9ar9cd7.pdf

Adverse effects of ciprofloxacin on testis apoptosis and sperm parameters in rats

The aim of this study was to investigate the efficacy and safety of ondansetron as an augmentative agent to fluvoxamine in the treatment of patients with obsessive-compulsive disorder (OCD). Forty-six men and women, aged 18-60 years, who fulfilled the diagnostic criteria of OCD on the basis of the DSM-IV-TR and had a Yale-Brown Obsessive Compulsive Scale (Y-BOCS) score of at least 21 were recruited into the study. The patients randomly received either ondansetron (8 mg/day) or placebo for 8 weeks. All patients received fluvoxamine (100 mg/day) for the first 4 weeks, followed by 200 mg/day for the rest of the trial. The patients were assessed using the Y-BOCS and the adverse event checklists at baseline, and the second, fourth, sixth, and eighth week. Forty-four patients completed the study. The Y-BOCS total score as well as the Y-BOCS obsession subscale score and compulsion subscale score showed significantly greater reduction in the ondansetron group than in the placebo group. There was no significant difference in adverse events between the two groups. In this 8-week double-blind randomized-controlled trial, ondansetron showed significant beneficial effect as an augmentative agent with fluvoxamine in patients with moderate to severe OCD and it was generally well tolerated.

Ondansetron or placebo in the augmentation of fluvoxamine response over 8 weeks in obsessive-compulsive disorder.

Dorema ammoniacum is a perennial herb which its gum resin is used in traditional medicine of Iran and also widely used in food, cosmetic and detergent industries.In the present study, in vitro cytotoxic activity of the essential oil from ripe fruits of D. ammoniacum was investigated against two human cancer (MCF and SW480) and two normal (HFSF and HFLP) cell lines. Ripe fruits of D. ammoniacum collected just in deciduous time were subjected to hydro-distillation to yield essential oil which was subsequently analyzed by GC and GC/MS. MTT assay used for cytotoxic activity.Among four cell lines tested SW480 and, MCF-7 are cancer lines and were more sensitive to D. ammoniacum oil than other two normal cell lines. On the basis of these results the essential oil D. ammoniacum has antimicrobial activity and low cytotoxicity activity provide a scientific basis for the traditional use.

/pdf/in-vitro-cytotoxic-activity-of-the-essential-oil-of-dorema-1908v23zla.pdf

Mahnaz Heidari

Papers

In Vitro Cytotoxicity of a New Epoxy Resin Root Canal Sealer

In vitro inhibitory effects of antioxidants on cytotoxicity of T-2 toxin.

Adverse effects of ciprofloxacin on testis apoptosis and sperm parameters in rats

Ondansetron or placebo in the augmentation of fluvoxamine response over 8 weeks in obsessive-compulsive disorder.

In vitro Cytotoxic Activity of the Essential Oil of Dorema ammoniacum D. Don.