Bacteria-derived chimeric toxins as potential anticancer agents.

Cancer is one of the major causes of death globally, requiring everlasting efforts to develop novel, specific, effective, and safe treatment strategies. Despite advances in recent years, chemotherapy, as the primary treatment for cancer, still faces limitations such as the lack of specificity, drug resistance, and treatment failure. Bacterial toxins have great potential to be used as anticancer agents and can boost the effectiveness of cancer chemotherapeutics. Bacterial toxins exert anticancer effects by affecting the cell cycle and apoptotic pathways and regulating tumorigenesis. Chimeric toxins, which are recombinant derivatives of bacterial toxins, have been developed to address the low specificity of their conventional peers. Through their targeting moieties, chimeric toxins can specifically and effectively detect and kill cancer cells. This review takes a comprehensive look at the anticancer properties of bacteria-derived toxins and discusses their potential applications as therapeutic options for integrative cancer treatment.

The effect of aromatherapy with rose essential oil on apparent anxiety in patients with myocardial infarction.

OBJECTIVES: Acute myocardial infarction (MI) and hospitalization are one of the most stressful situations for many patients. Aromatherapy is a branch of the complementary medicine that is effective in anxiety. The present study aims to determine the effect of aromatherapy with rose essential oil (REO) on apparent anxiety in patients with acute MI. METHODS: This randomized clinical trial was carried out on patients with acute MI admitted to the cardiac ward of Heshmatieh Hospital in Sabzevar. Eighty patients were randomly assigned to two aromas and placebo groups, who received three drops of REO or placebo by inhalation three times a day for 3 days. Before and after the intervention, patients' anxiety levels were measured by the Spielberger questionnaire. Data were analyzed by chi-square and the independent and paired and t-tests. RESULTS: Before the intervention, the mean of apparent anxiety was not significantly different in the intervention and control groups (48.44 ± 3.81 and 51.38 ± 7.21, respectively, p=0.16) while this parameter was significant after the intervention in both experimental groups (47.27 ± 7.11 and 44.16 ± 4.63, respectively, p=0.000), with a reduction in the mean of apparent anxiety in the intervention group. Moreover, the results of paired t-test revealed that the anxiety scores decreased significantly in the test group before and after the intervention (51.38 ± 7.21 and 44.16 ± 4.63, p=0.000). CONCLUSIONS: Considering the positive effects of REO used in this study to reduce anxiety in patients with acute MI, the use of REO is recommended as a complementary treatment to reduce anxiety in these patients.

4-Hydroxyisophthalic acid from Decalepis hamiltonii rescues the neurobehavioral deficit in transgenic Drosophila model of taupathies.

Oxidative stress is one of the major etiological factors implicated in pathogenesis of neurodegenerative diseases. Since neurons are more sensitive to oxidative damage there is an increasing interest in developing novel antioxidant therapies, especially herbal preparations due to their safety profile and high efficiency. In this regard, the neuroprotective potential of a novel antioxidant compound, 4-hydroxyisophthalic acid (4-HIPA) isolated from aqueous extract of Decalepis hamiltonii roots was examined using transgenic Drosophila model of taupathy expressing wild-type and mutant forms of 2N4R isoform of human microtubule associated protein tau (MAPT). Taupathy model flies showed cognitive deficits in olfactory memory and deteriorated circadian rhythm of locomotory activities. Administration of 0.1 mg/ml 4-HIPA, markedly enhanced their olfactory memory performance and restored circadian rhythmicity of the transgenic flies locomotory behavior to the normal range. The mechanism of action that underlies 4-HIPA neuroprotection involves enhancement in efficiency of cellular antioxidant defense system by means of elevation in antioxidant enzyme activities and attenuation of oxidative stress. The molecule could positively affect the activity of neurotransmitter enzymes, which in turn enhances neuronal function and ameliorates the Tau-induced neurobehavioral deficits. Our findings showed that 4-HIPA can be considered as a suitable therapeutic candidate for drug development towards treatment of neurodegenerative disorders.

The healing effect of scrophularia striata on experimental burn wounds infected to pseudomonas aeruginosa in rat.

BACKGROUND: The cause of death in burn patients after 48 hours of hospitalization has been reported to be bacterial infections. Recently, due to the compounds accelerating the healing process and the intense reduction of treatment side effects, medicinal plants are used to cure burn wound infections. This study aims to investigate the medicinal effect of the ethanolic extract of Scrophularia striata on burn wound infection in in-vivo and in-vitro in comparison with silver sulfadiazine (SSD). METHODS: One hundred and fifty male Sprague Dawley rats were divided into 3 equal groups. A hot plate of 1×1cm was used to create second degree burn wounds. The ethanolic extract of S. striata was provided through percolation method. Group 1 was treated with SSD, group 2 with S. striata, and group 3 was considered as control group. All animals were infected to Pseudomonas aeruginosa. On days 3, 7, 10, 14, and 21 after burn wound injury, the animals were euthanized and were evaluated histologically. The MIC and MBC were determined using the micro dilution method. RESULTS: The rate of wound healing was significantly greater in S. striata group in comparison to SSD and control groups. CONCLUSION: S. striata contains was shown to have anti-bacterial and wound healing effects while this effect was significantly more than SSD denoting to its use when needed for burn wounds infected to P. aeruginosa.

Modulatory effect of Decalepis hamiltonii on ethanol-induced toxicity in transgenic Drosophila model of Parkinson's disease.

Overexpression of human α-synuclein gene in Drosophila can reduce lifespan, and we have performed lifespan assay for A30P and A53Tα-synuclein transgenic and control (elav-GAL4, UAS-A30P, UAS-A53T) flies. Our results showed reduced lifespan of transgenic flies compared to controls. We have also investigated behavioral responses, levels of reactive oxygen species (ROS) and lipid peroxidation (LPO) and activities of catalase (CAT) and superoxide dismutase (SOD) in a combined genetic-toxin model (Ethanol-A30P or A53Tα-synuclein models) and controls. Our results showed that sedation time (ST50) of A30P or A53Tα-synuclein PD model flies was significantly lower while recovery time (RC50) of them was remarkably higher compared to control flies. The levels of oxidative markers (ROS and LPO) were significantly higher and the activities of CAT and SOD were lower in transgenic flies that underwent ethanol exposure compared to control. Based on our earlier studies on antioxidant properties of isolated and characterized molecules from Decalepis hamiltonii (Dh) root extract, its protective effect in this combined toxicity model has been investigated. Surprisingly, Dh treatment increased ST50 and decreased RC50 values of transgenic flies. Moreover, we showed that Dh pre-treatment could decrease the levels of ROS and LPO and increase the activities of CAT and SOD in the ethanol-α-synuclein model. This is the first report on protective effects of natural antioxidants in A30P or A53Tα-synuclein PD model flies against oxidative stress induced by ethanol.

Neuroprotective effect of Decalepis hamiltonii in paraquat-induced neurotoxicity in Drosophila melanogaster: biochemical and behavioral evidences.

In this paper, we have demonstrated for the first time, the antioxidant and neuroprotective effects of Decalepis hamiltonii (Dh) root extract against paraquat (PQ)-induced oxidative stress and neurotoxicity in Drosophila melanogaster. Exposure of adult D. melanogaster (Oregon K) to PQ induced oxidative stress as evidenced by glutathione depletion, lipid peroxidation and enhanced activities of antioxidant enzymes such as catalase, superoxide dismutase as well as elevated levels of acetylcholine esterase. Pretreatment of flies by feeding with Dh extract (0.1, 0.5 %) for 14 days boosted the activities of antioxidant enzymes and prevented the PQ-induced oxidative stress. Dietary feeding of Dh extract prior to PQ exposure showed a lower incidence of mortality and enhanced motor activities of flies in a negative geotaxis assay; both suggesting the neuroprotective potential of Dh. Based on the results, we contemplate that the roots of Dh might prevent and ameliorate the human diseases caused by oxidative stress. The neuroprotective action of Dh can be attributed to the antioxidant constituents while the precise mechanism of its action needs further investigations.

Decalepis hamiltonii root extract attenuates the age-related decline in the cognitive function in Drosophila melanogaster.

Age-associated accumulation of oxidative damage linked to decline of antioxidant defense mechanism, leads to impairment of cognitive function in many organisms. These damages can pass through generations and affect the cognitive quality of progenies. In Drosophila, classical olfactory conditioning results in the formation of different types of memory. Age-related memory impairment (AMI) causes reduction in middle term memory (MTM) and parental senescence causes decline in short-term memory (STM) of the offspring. We have further examined the neuromodulatory effect of Decalepis hamiltonii (Dh) root extract, which is a cocktail of novel antioxidant molecules, on the biochemical oxidative defenses in relation to cognitive ability of the aged flies and their offspring. There is a strong correlation between the age-related decline in the activity of the antioxidant enzymes and the lower cognitive ability of the aged flies and their offspring. Feeding of aged flies in the diet containing 0.1% Dh, markedly enhances the cognitive ability of both aged flies and their offspring which is associated with enhanced antioxidant defenses as evident for the activity of superoxide dismutase (SOD) and catalase. Our findings, for the first time, show that the antioxidant-rich Dh root extract attenuates the age-related decline in cognitive ability of Drosophila, and also shows ameliorative effect on the memory of the offspring.