Dual anticancer activity of Aspergillus nidulans pigment and Ionizing γ-Radiation on human larynx carcinoma cell line.

BACKGROUND: Fungi are a readily available source of naturally generated colored compounds. These compounds might be used as radiosensitizers for treating cancer cells. METHODS: Aspergillus nidulans was examined for its color-producing ability in Potato dextrose agar (PDA) broth medium. The pigment was characterized by Ultraviolet (UV) spectrophotometer and Gas Chromatography Mass Spectrometry (GC/MS). Pigment extracts from A. nidulans were studied for their cytotoxic effects on the growth of human larynx carcinoma cell line (HEp-2) with or without exposure to γ-radiation at three different doses (5, 10, and 15 Gy). A. nidulans pigment cytotoxic activity was tested against normal Vero cells. Cell apoptosis was studied using flow cytometry. Gene expression of P53, Caspase 3 and Bcl-2 were quantified. RESULTS: Ultraviolet spectrum and GC/MS revealed the ability of Aspergillus nidulans to produce Rhodopin pigment. HEp-2 cells treated with A. nidulans pigment only give IC50 about 208 µg/ml. In contrast, when treated with the pigment +10 Gy Î³-radiation, it give about 115 µg/ml. However, for normal cells, lower cytotoxic activity was detected. Treatment with pigment (208 g/mL) caused about 50% ± 1.0 total apoptosis level and gene expression of P53: 2.3 fold and Caspase 3: 1.84 fold in respect to untreated HEp-2), while Bcl-2 was decreased (Bcl-2: 0.63 fold in respect to untreated HEp-2). Furthermore, treated with pigment (115 µg/mL) + 10Gy caused about 47.41% ± 1.7 total apoptosis level and P53: 2.53 fold and Caspase 3: 2.0 fold in respect to untreated HEp-2, while Bcl-2 was downregulated (Bcl-2: 0.61 fold in respect to untreated HEp-2). CONCLUSION: This study concluded that the anti-cancer activity of Aspergillus nidulans pigment was enhanced by ionizing radiation at 10 Gy, as well as its low cytotoxic activity against normal Vero cells.

Orange peels and Chlorella vulgaris supplementation ameliorate gamma radiation-induced oxidative stress by regulating TGF-ß and NOX2/NOX4 signaling pathways.

Numerous studies revealed that Chlorella vulgaris and orange peels are potential sources for many valuable compounds such as flavonoids, which are natural polyphenols with antioxidant capacities that lessen oxidative stress via suppressing ROS levels. Thus, this study was designed to investigate their radioprotective efficiency either alone or in combination as natural food supplements. Sixty-four male Albino rats were divided into eight groups (n = 8) as follows: control, orange peel (10% in diet), C. vulgaris (1% in diet), orange peel + C. vulgaris, gamma irradiated (2Gy twice per week up to 8Gy), orange peel + gamma irradiation, C. vulgaris + gamma irradiation, and orange peel + C. vulgaris + gamma irradiation. After the experiment, blood serums were collected for biochemical analysis, whole bloods were collected for blood picture, bone marrows were collected for GSH, MDA, TGF-ß, NOX2 and NOX4, and liver tissues were collected for histopathological evaluation. Current study revealed that exposure to gamma irradiation induced a significant disturbance in liver function markers (ALT and AST), kidney function markers (urea and creatinine), cholesterol and triglycerides levels in serum. In addition, a significant decrease in WBCs, RBCs, PLT, and Hb in blood of irradiated rats. Moreover, a significant elevation in TGF-ß, NOX2, NOX4 activities, and MDA level, while showed a marked decrease in GSH concentration. Furthermore, hepatic inflammation appeared in the histopathological examination. Orange peels or C. vulgaris treatments showed acceptable amelioration in all measured parameters, combination between orange peels and C. vulgaris showed statistically significant additive amelioration in radiation induced disturbance.

Antitumor Activity of Chitosan-Coated Iron Oxide Nanocomposite Against Hepatocellular Carcinoma in Animal Models.

Hepatocellular carcinoma (HCC) is among the most prevalent and lethal cancers worldwide. Chitosan-coated iron oxide nanocomposite (Fe3O4/Cs) is a promising bio-nanomaterial for many biological applications. The objective of this research was to evaluate the anticancer efficacy of Fe3O4/Cs against HCC in animal models. Fe3O4 nanoparticles were prepared and added to chitosan solution; then, the mixture was exposed to gamma radiation at a dose of 20 kGy. Rats have received diethylnitrosamine (DEN) orally at a dose of 20 mg/kg body weight 5 times per week during a period of 10 weeks to induce HCC and then have received Fe3O4/Cs intraperitoneal injection at a dose of 50 mg/kg body weight 3 times per week during a period of 4 weeks. After the last dose of Fe3O4/Cs administration, animals were sacrificed. DEN induced upregulation of PI3K/Akt/mTOR and MAPK (ERK, JNK, P38) signaling pathways and inflammatory markers (TLR4, iNOS, and TNF-α). DEN also decreases cleaved caspase-3 and increases liver enzymes (ALT, AST, and GGT) activities. Administration of Fe3O4/Cs significantly ameliorated the above-mentioned parameters.

Oral manifestations of eating disorders in adolescent patients. A review.

AIM: Eating disorders (ED) are a group of psychopathological disorders that affect the patient's relationship with food and his own body and that are manifested mainly in adolescence and in young-adult age. ED include anorexia nervosa (AN), bulimia nervosa (BN) and other eating disorders as classified in the DMS-V. ED can result in several oral and dental manifestations that often occur in the early stages of ED and may allow early detection. The aim of the study is to describe the different oral and dental manifestations in patients with ED in order to offer a classification for their identification during an extra/intra-oral examination. METHODS: A search on PubMed, Medline and Cochrane Library data bases has been performed. RESULTS: Oral manifestations in ED patients include a variety of signs and symptoms, which involve the oral mucosa and perioral tissues (exfoliative cheilitis, labial erythema, atrophic glossitis, glossodynia, yellow-orange colouration of the soft palate, cheek/lip biting, candidiasis), the teeth (dental erosion, tooth hypersensitivity, dental caries), periodontal diseases, and salivary manifestations (sialoadenosis, alterations in salivary flow). The oral signs are caused by a number of factors, including nutritional deficiencies and consequent metabolic changes, poor personal hygiene, altered eating habits and pharmacological therapies. There is a very specific link between oral manifestations and ED in the presence of self-induced vomiting. CONCLUSION: The paediatric dentist may be the first professional to detect the clinical signs thus improving the interception, early diagnosis, characterisation and prognosis of ED. In addition, the oral manifestations of ED can cause alterations of the oral function, discomfort, oral pain, and worsen aesthetics of the face and the quality of life.

Impact of lockdown on children's lifestyle and their collaboration during dental sessions.

AIM: To analyse lifestyle of Italian families during lockdown, evaluating its possible impact on the collaboration of children with the paediatric dentist and associated predictive factors. MATERIALS AND METHODS: Only patients aged between 3 and 16 years, who had started treatment before the lockdown and had spent this periodwith both parents were included in the study. The interviews were carried out using an anonymous questionnaire that assessed school and play activities, the type of diet, the time dedicated to home oral hygiene and the activities carried out with parents. Parents' work situation during lockdown was included to correlate it with time spent at home. The Frankl Behavior Rating Scale was used to determine the degree of cooperation during dental sessions pre- and post-lockdown. Chi-square test and Fisher's Exact tests were used to identify statistical associations of improvement with each categorical variable. Student's t-test was used to highlight the differences in mean values of continuous variables between subjects considered more cooperative and unimproved subjects. Hosmer-Lemeshow test was used to assess the goodness-of-fit of the model. Assumption of linearity of independent variables and log-odds were assessed by Box-Tidwell transformation. Final selection was carried out using the Akaike criterion and all statistical analyses were carried out using the STATA statistical software package. RESULTS: The sample consisted of 212 patients (103F; 109M). The age ranged between 3 and 16 years with an average age of 9.03 years; 82.08% (95% CI 76.24-86.99) of the subjects showed an improvement in collaboration compared to pre-lockdown. Logistic analysis reveals a statistically significant increase of the odds of improvement in patients with a lower pre-lockdown collaboration (OR: 6.05, p = 0.001), in children with a parental presence at home (jobless, OR : 30.55, p <0.001; in "smart working", OR: 23.06, p <0.001) when compared to children whose parents work away from home. From a further exploratory analysis, time dedicated to home oral hygiene was increased if associated with an increased presence of the parents at home (p = 0.015). CONCLUSION: Changes in family routines and increased parental presence at home, during the COVID-19 pandemic lockdown, are associated with improved collaboration of children during dental sessions. A statistical association between the increase in time spent on oral hygiene and the increased presence of parents at home was found.

Enhancement the Mycosynthesis of Selenium Nanoparticles by Using Gamma Radiation.

Selenium is a fundamental trace element of the living system. Microorganisms play a crucial role in the selenium cycle, both in the environment and in life. Biogenic selenium nanoparticles have shown promising prospects for use in medicine as an antioxidant and anticancer agent. In this study, SeNPs were biosynthesized by Penicillium citrinum. The spore suspension which was previously prepared was exposed to different doses of gamma radiation (10, 20, 30, 50, and 60 Gy). SeNPs were then produced by an irradiated P citrinum. UV spectroscopy, transmission electron microscopy, X-ray diffraction, and GSH content were assayed to evaluate the probability of P citrinum synthesizing SeNPs. In conclusion, irradiation of P citrinum by gamma ray enhances the mycosynthesis of SeNPs.

Boswellic Acid Synergizes With Low-Level Ionizing Radiation to Modulate Bisphenol Induced-Lung Toxicity in Rats by Inhibiting JNK/ERK/c-Fos Pathway.

Bisphenol A (BPA) is a low molecular weight chemical compound that has a deleterious effect on the endocrine system. It was used in plastics manufacturing with injurious effects on different body systems. Occupational exposure to low-level ionizing radiation (<1 Gy) is shown to attenuate an established inflammatory process and therefore enhance cell protection. Therefore, the objective of this study was to investigate the protective effect of boswellic acid (BA) accompanied by whole-body low-dose gamma radiation (γ-R) against BPA-induced lung toxicity in male albino rats. BPA intoxication induced with 500 mg/kg BW. Rats received 50 mg BA/kg BW by gastric gavage concomitant with 0.5 Gy γ-R over 4 weeks. The immunoblotting and biochemical results revealed that BA and/or γ-R inhibited BPA-induced lung toxicity by reducing oxidative damage biomolecules; (MDA and NADPH oxidase gene expression), inflammatory indices (MPO, TNF-α, IL-6, and gene expression of CXCR-4). Moreover, BA and or/γ-R ameliorated the lung inflammation via regulation of the JNK/ERK/c-Fos and Nrf2/ HO-1 signaling pathways. Interestingly, our data demonstrated that BA in synergistic interaction with γ-R is efficacious control against BPA-induced lung injury via anti-oxidant mediated anti-inflammatory activities.

Modulatory effect of zingerone against cisplatin or γ-irradiation induced hepatotoxicity by molecular targeting regulation.

Zingerone (ZO) is an ingredient of ginger (Zingiber officinale) which has different pharmacological properties. The objective of this research was to evaluate the protective effect of ZO against Cisplatin (Cis) or γ-Irradiation (IR)-induced hepatotoxicity in rats. ZO was given orally for consecutive 14 days prior to the treatment with Cis or exposure to IR at 15th day. Animals were sacrificed at the 23rd day. Cis or IR induced a marked increase in MAPK signal transduction as evidenced by increased p38 MAPK, JNK and ErK1/2. CYP2E1 and NADPH oxidase were significantly up-regulated. Inflammatory markers (TLR4, iNOS, COX-2 and MPO) and liver enzymes (AST, ALT and ALP) activities were also increased. Administration of ZO significantly ameliorated the above mentioned parameters.

Aerobic exercise and Orexin A: role of sympathetic activity and redox system.

Aerobic exercise is associated with the sympathetic activation evoking adaptive responses to sustain muscle engagement. Physical exercise can cause alterations in the cardiovascular activity and cellular stress may occur which could be marked by either heart rate (HR), or galvanic skin response (GSR). Moderate plasma levels of reactive oxygen species (ROS) are considered as health markers, absolving to important roles such as adaptive cellular responses to exercise. Orexin A, a hypothalamic peptide, causes a widespread stimulation of the sympathetic nervous system, playing a role in many physiological functions.

Mastication induces long-term increases in blood perfusion of the trigeminal principal nucleus.

Understanding mechanisms for vessel tone regulation within the trigeminal nuclei is of great interest because some headache syndromes are due to dysregulation of such mechanisms. Previous experiments on animal models suggest that mastication may alter neuron metabolism and blood supply in these nuclei. To investigate this hypothesis in humans, arterial spin-labeling magnetic resonance imaging (MRI) was used to measure blood perfusion within the principal trigeminal nucleus (Vp) and in the dorsolateral-midbrain (DM, including the mesencephalic trigeminal nucleus) in healthy volunteers, before and immediately after a mastication exercise consisting of chewing a gum on one side of the mouth for 1 h at 1 bite/s. The side preference for masticating was evaluated with a chewing test and the volume of the masseter muscle was measured on T1-weighted MRI scans. The results demonstrated that the mastication exercise caused a perfusion increase within the Vp, but not in the DM. This change was correlated to the preference score for the side where the exercise took place. Moreover, the basal Vp perfusion was correlated to the masseter volume. These results indicate that the local vascular tone of the trigeminal nuclei can be constitutively altered by the chewing practice and by strong or sustained chewing.

Use of inertial measurement units to assess age-related changes in gait kinematics in an active population.

To study mobility in older populations it can be advantageous to use portable gait analysis systems, such as inertial measurement units (IMUs), which can be used in the community. To define a normal range, 136 active subjects were recruited with an age range of 18 to 97. Four IMUs were attached to the subjects, one on each thigh and shank. Subjects were asked to walk 10 m at their own self-selected speed. The ranges of motion of thigh, shank, and knee in both swing and stance phase were calculated, in addition to stride duration. Thigh, shank, and knee range of movement in swing and stance were significantly different only in the > 80 age group. Regressions of angle against age showed a cubic relationship. Stride duration showed a weak linear relationship with age, increasing by approximately 0.1% per year.

Autonomic nervous system in the control of energy balance and body weight: personal contributions.

The prevalence of obesity is increasing in the industrialized world, so that the World Health Organization considers obesity as a "pandemia" in rich populations. The autonomic nervous system plays a crucial role in the control of energy balance and body weight. This review summarizes our own data and perspectives, emphasizing the influence exerted by autonomic nervous system on energy expenditure and food intake, which are able to determine the body weight. Activation of the sympathetic discharge causes an increase in energy expenditure and a decrease in food intake, while reduction of food intake and body weight loss determines a reduction of the sympathetic activity. On the other hand, pathophysiological mechanisms of the obesity involve alterations of the sympathetic nervous system in accordance with the "Mona Lisa Hypothesis," an acronym for "most obesities known are low in sympathetic activity." Furthermore, the parasympathetic influences on the energy expenditure are analyzed in this review, showing that an increase in parasympathetic activity can induce a paradoxical enhancement of energy consumption.

Enhanced parasympathetic activity of sportive women is paradoxically associated to enhanced resting energy expenditure.

The resting energy expenditure and the adaptation of the autonomic nervous system induced by sport activities in sedentary women and in female professional basketball players have been studied. Resting energy expenditure, body composition and the level of activity of the autonomic nervous system were measured before and after a period of six months. The physical activity induced an increase in resting energy expenditure and free fat mass without variations in body weight. Basketball players showed a significant increase in the parasympathetic activity, measured by the power spectral analysis of the heart rate variability. These findings demonstrate that resting energy expenditure is higher in the athletes than in sedentary women, despite the augmented parasympathetic activity that is usually related to lower energy expenditure.

Mastication overload causes an increase in O2- production into the subnucleus oralis of the spinal trigeminal nucleus.

The aim of the present study was to evaluate the production of superoxide anion (O(2)(-)) in the trigeminal complex nuclei after a functional mechanical overload of the teeth due to the preference for masticating on one side in rats. The preference for masticating on one side was induced by the discomfort due to a small abrasion of one molar; such lateralisation in mastication was confirmed by electromyography. The production of O(2)(-) was evaluated in the trigeminal nuclei by fluorescence microscopy after an injection of dihydroethidium. The results showed that there was an increased production of O(2)(-) in the subnucleus oralis of the spinal trigeminal nucleus in the same side where the mastication was preferred. This result demonstrates that an increased activity of non-painful sensory neurons can enhance the production of reactive oxygen species within the central second order sensory nuclei.

Inhibition of prostaglandin synthesis reduces the induction of MyoD expression in rat soleus muscle.

MyoD is a myogenic regulatory factor with a critical role in skeletal muscle development and regeneration. As muscle regeneration comes with an inflammatory process, it has been proposed that the inflammatory cells can play an important role in the induction of muscle fibres regeneration. The aim of the present work was to verify if a cyclooxygenase inhibitory drug (ketoprofen) would alter the normal expression of MyoD in a regenerating rat soleus muscle after an over-load lesion. Using immunohistochemical techniques, the numbers of m-cadherin-positive cells, a selective marker of satellite cells, and MyoD-positive cells were evaluated in functionally overloaded rat soleus muscles 4 days after a gastrocnemius tendon cut. The same study was conducted either with four rats injected with ketoprofen (100 mg/kg b.w./day) or with four rats injected with saline solution. The data obtained showed a very large decrease in the number of MyoD positive/m-cadherin positive cells in the ketoprofen injected group compared to the control group. Although further studies are needed to elucidate the sequence of biochemical events that induce a reduction of MyoD expression due to ketoprofen, the results demonstrate that prostaglandin synthesis is required for the induction of MyoD expression and that ketoprofen can affect this expression, with possible adverse effects on muscle regeneration.

Espresso coffee increases parasympathetic activity in young, healthy people.

Caffeine induces modifications of activity of the autonomic nervous system. This study analyzed the effect of a cup of espresso coffee on the heart rate variability (HRV) power spectral analysis, which is a method providing evaluation of the sympathetic and parasympathetic discharge. In young, healthy sedentary subjects (10 male, 10 female; aged 25-30 years), the HRV-power spectrum was evaluated over a period of 150 min after the administration of espresso coffee (caffeine, 75 mg) or decaffeinated coffee (caffeine, < 18 mg) in supine and seated position. Absolute values of the spectrum were summed in low (LF) and high frequencies (HF). The LF and HF spectra were used to estimate the sympathetic and parasympathetic activity, respectively. In the supine position, coffee increases HF, while decaffeinated coffee causes little modifications of HF. In the seated position, HF is not modified by coffee or decaffeinated coffee. Coffee and decaffeinated coffee do not induce any modification of LF in both positions. This experiment indicates that espresso coffee influences parasympathetic activity in the supine position.

Resting energy expenditure and fat-free mass do not decline during aging in severely obese women.

BACKGROUND & AIMS: Few studies have investigated the age-related modification of resting energy expenditure (REE) and free fat mass (FFM) in severe obesity. This cross-sectional study analyzed REE and FFM in severely and moderately obese women and in lean subjects at different ages to find the possible differences between obese and lean subjects during aging. METHODS: Sedentary women (n=261) were divided into three groups with different body mass indexes (BMIs): 20.0-24.9; 30-34.9; >40 kg/m(2). Each group was then divided into five subgroups: 20-29; 30-39; 40-49; 50-59; 60-69 years. REE was measured with an indirect calorimetric device. The FFM was calculated by bioelectric impedance. RESULTS: The REE in severely obese women was higher than the REE in lean or moderately obese women. The FFM of severely obese women was lower than that of moderately obese or lean women. The aging induced reductions of the REE and FFM in lean and moderately obese subjects, but not in women with severe obesity. CONCLUSIONS: This experiment indicates that REE and FFM do not decline during aging in women with BMI>40, suggesting that the severe obesity induces different age-related adaptations of metabolism and body composition.

Cortical spreading depression induces the expression of iNOS, HIF-1alpha, and LDH-A.

The mechanisms of tolerance to subsequent episodes of ischemia induced by cortical spreading depression (CSD) are not clear. The effects of CSD on the expression of inducible nitric oxide synthase (iNOS), hypoxia inducible factor-1alpha (HIF-1alpha), and lactate dehydrogenase-A (LDH-A) were evaluated in the present experiment. Unilateral CSD was induced in Sprague-Dawley rats by application of KCl on the right cortex and the mRNA levels of iNOS, HIF-1alpha, and LDH-A were evaluated at 15 min, 2 h, 4 h, 6 h or 24 h after CSD. RT-PCR analysis showed: 1) an increase of iNOS mRNA at 15 min, 2 h, 4 h; 2) an increase of HIF-1alpha mRNA at 6 h; 3) an increase of LDH-A mRNA at 4 h. In situ hybridization with specific digoxigenin-labeled oligonucleotides revealed that the mRNA levels were increased at 15 min-2 h for iNOS, 2-4 h for LDH-A and 6 h for HIF-1 after CSD. Immunohistochemistry analysis revealed that levels of iNOS and HIF-1alpha were increased, respectively, at 2 h and 6 h after CSD. These data suggest that CSD promotes the expression of iNOS, HIF-1alpha, and LDH-A in nervous cells giving a neuroprotective effect.

Olanzapine blocks the sympathetic and hyperthermic reactions due to cerebral injection of orexin A.

Since experiments regarding a possible relation between olanzapine and orexin A has been scarcely reported in international literature, this experiment tested the effect of olanzapine on the sympathetic and thermogenic effects induced by orexin A. The firing rates of the sympathetic nerves to interscapular brown adipose tissue (IBAT), along with IBAT, colonic temperatures and heart rate were monitored in urethane-anesthetized male Sprague-Dawley rats before an injection of orexin A (1.5 nmol) into the lateral cerebral ventricle and over a period of 150 min after the injection. The same variables were monitored in rats with an intraperitoneal administration of olanzapine (10mg/kg bw), injected 30 min before the orexin administration. The results show that orexin A increases the sympathetic firing rate, IBAT, colonic temperatures and heart rate. This increase is blocked by the injection of olanzapine. These findings indicate that olanzapine affects the complex reactions related to activation of orexinergic system.

Intracerebroventricular injection of oxidant and antioxidant molecules affects long-term potentiation in urethane anaesthetized rats.

Production of superoxide anions in the incubation medium of hippocampal slices can induce long-term potentiation (LTP). Other reactive oxygen species (ROS) such as hydrogen peroxide are able to modulate LTP and are likely to be involved in aging mechanisms. The present study explored whether intracerebro-ventricular (ICV) injection of oxidant or antioxidant molecules could affect LTP in vivo. With this aim in mind, field excitatory post-synaptic potentials (fEPSPs) elicited by stimulation of the perforant pathway were recorded in the dentate gyrus of the hippocampal formation in urethane-anesthetized rats. N-acetyl-L-cysteine, hydrogen peroxide (H2O2) or hypoxanthine/xanthine-oxidase solution (a superoxide producing system) were administrated by ICV injection. The control was represented by a group injected with saline ICV. Ten minutes after the injection, LTP was induced in the granule cells of the dentate gyrus by high frequency stimulation of the perforant pathway. Neither the H(2)O(2) injection or the N-acetyl-L-cysteine injection caused any variation in the fEPSP at the 10-min post-injection time point, whereas the superoxide generating system caused a significant increase in the fEPSP. Moreover, at 60 min after tetanic stimulation, all treatments attenuated LTP compared with the control group. These results show that ICV administration of oxidant or antioxidant molecules can modulate LTP in vivo in the dentate gyrus. Particularly, a superoxide producing system can induce potentiation of the synaptic response. Interestingly, ICV injection of oxidants or antioxidants prevented a full expression of LTP compared to the saline injection.