Impact of atorvastatin and mesenchymal stem cells combined with ivermectin on murine trichinellosis.

Trichinellosis is one of the global food-borne parasitic diseases that can cause severe tissue damage. The traditionally used drugs for the treatment of trichinellosis have limited efficacy against the encysted larvae in the muscular phase of the disease. Therefore, this study aimed to evaluate the role of atorvastatin and mesenchymal stem cells combined with ivermectin against different phases of Trichinella in experimentally infected mice. A total of 120 male Swiss albino mice were divided into two major groups (n = 60 of each), intestinal and muscular phases. Then, each group was subdivided into 10 subgroups (n = 6); non-infected control, infected non-treated control, infected ivermectin treated, infected atorvastatin treated, infected mesenchymal stem cells treated, infected combined ivermectin and atorvastatin treated, infected combined mesenchymal stem cells and ivermectin treated, infected combined mesenchymal stem cells and atorvastatin treated, infected combined mesenchymal stem cells and a full dose of (ivermectin and atorvastatin) treated, and infected combined mesenchymal stem cells and half dose of (ivermectin and atorvastatin) treated. Mice were sacrificed at days 5 and 35 post-infection for the intestinal and muscular phases, respectively. The assessment was performed through many parameters, including counting the adult intestinal worms and muscular encysted larvae, besides histopathological examination of the underlying tissues. Moreover, a biochemical assay for the inflammatory and oxidative stress marker levels was conducted. In addition, levels of immunohistochemical CD31 and VEGF gene expression as markers of angiogenesis during the muscular phase were investigated. The combined mesenchymal stem cells and atorvastatin added to ivermectin showed the highest significant reduction in adult worms and encysted larvae counts, the most noticeable improvement of the histopathological changes, the most potent anti-inflammatory (lowest level of IL-17) and anti-angiogenic (lowest expression of CD31 and VEGF) activities, and also revealed the highly effective one to relieve the oxidative stress (lowest level of SOD, GSH, and lipid peroxidase enzymes). These observed outcomes indicate that adding mesenchymal stem cells and atorvastatin to ivermectin synergistically potentiates its therapeutic efficacy and provides a promising candidate against trichinellosis.

Ultrastructural changes and IgA modulatory effect of commercial prebiotic and probiotic in murine giardiasis.

Giardiasis, a parasitic infection of the gastrointestinal tract, is prevalent worldwide. The integrity of the intestinal epithelial barrier plays an important defensive role in giardiasis, and as Oral supplementation with prebiotics and probiotics is known to reinforce the intestinal barrier in many gastrointestinal diseases, this study assessed the effects of prebiotic and probiotic supplementation in giardiasis and compared the results with those obtained after nitazoxanide therapy. Swiss albino male lab-bred mice (n = 50) were divided into three major groups; Group I (control group), i.e., negative (noninfected nontreated) and positive controls (infected nontreated); Group II (preventive group), in which mice were provided prebiotic, probiotic, or a combination for 7 days before of infection, and Group III (therapy group), in which mice were administered prebiotic, probiotic, combined supplements and nitazoxanide from day 12 post-infection. The assessment was achieved through Giardia cyst count, histopathological examination and ultrastructure study. Also, Serological and immunohistochemical parameters were done to evaluate the modulation of IgA levels. Oral supplementation with prebiotic and probiotic, either before or after infection (in preventive or therapy groups respectively) resulted in a significant reduction in Giardia cyst shedding. Remarkable histological and ultrastructure improvement in the intestinal changes, along with a significant increase in the serological and immunohistochemical IgA levels, were seen in mice provided combined supplements and nitazoxanide (in therapy group). Thus, our results indicate that combined prebiotic and probiotic supplementation has promising anti-Giardia activity and that it can restore intestinal structures and modulate IgA response, apart from providing synergistic effects when added to nitazoxanide.

The effect of Alnus incana (L.) Moench extracts in ameliorating iron overload-induced hepatotoxicity in male albino rats.

Iron overload causes multiorgan dysfunction and serious damage. Alnus incana from the family Betulaceae, widely distributed in North America, is used for treating diseases. In this study, we investigated the iron chelating, antioxidant, anti-inflammatory, and antiapoptotic activities of the total and butanol extract from Alnus incana in iron-overloaded rats and identified the bioactive components in both extracts using liquid chromatography-mass spectrometry. We induced iron overload in the rats via six intramuscular injections of 12.5 mg iron dextran/100 g body weight for 30 days. The rats were then administered 60 mg ferrous sulfate /kg body weight once daily using a gastric tube. The total and butanol extracts were given orally, and the reference drug (deferoxamine) was administered subcutaneously for another month. After two months, we evaluated the biochemical, histopathological, histochemical, and immunohistochemical parameters. Iron overload significantly increased the serum iron level, liver biomarker activities, hepatic iron content, malondialdehyde, tumor necrosis factor-alpha, and caspase-3 levels. It also substantially (P < 0.05) reduced serum albumin, total protein, and total bilirubin content, and hepatic reduced glutathione levels. It caused severe histopathological alterations compared to the control rats, which were markedly (P < 0.05) ameliorated after treatment. The total extract exhibited significantly higher anti-inflammatory and antiapoptotic activities but lower antioxidant and iron-chelating activities than the butanol extract. Several polyphenolic compounds, including flavonoids and phenolic acids, were detected by ultraperformance liquid chromatography-electrospray ionization-quadrupole time-of-flight mass spectrometry (UPLC-ESI-QTOF-MS) analysis. Our findings suggest that both extracts might alleviate iron overload-induced hepatoxicity and other pathological conditions characterized by hepatic iron overload, including thalassemia and sickle-cell anemia.

Transcriptome-wide association analyses identify an association between ARL14EP and polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is a common endocrine disorder, which is accompanied by a variety of comorbidities including metabolic, reproductive, and psychiatric disorders. Genome-wide association studies have identified several genetic variants that are associated with PCOS. However, these variants often occur outside of coding regions and require further investigation to understand their contribution to PCOS. A transcriptome-wide association study (TWAS) was performed to uncover heritable gene expression profiles that are associated with PCOS in two independent cohorts. Causal gene prioritization was subsequently performed and expression of genes prioritized through these analyses was examined in 49 PCOS patients and 30 controls. TWAS analyses revealed that increased expression of ARL14EP was significantly associated with PCOS risk in the discovery (P = 1.6 × 10-6) and replication cohorts (P = 2.0 × 10-13). Gene prioritization pipelines provided further evidence that ARL14EP is the most likely causal gene at this locus. ARL14EP gene expression was shown to be significantly different between PCOS cases and controls, after adjusting for body mass index, age and testosterone levels (P = 1.2 × 10-13). This study has provided evidence for the role of ARL14EP in PCOS. Given that ARL14EP has been reported to play an important role in chromatin remodeling, variants affecting the expression of ARL14EP may also affect the expression of other genes that contribute to PCOS pathogenesis.

Hypoxia pretreatment enhances the therapeutic potential of mesenchymal stem cells (BMSCs) on ozone-induced lung injury in rats.

Ozone (O3) gas is a double-sided weapon. It provides a shield that protects life on earth from the harmful ultraviolet (UV) rays, but ground-level O3 is considered an urban air pollutant. So, a rat model of chronic O3 inhalation was established to assess the biochemical and morphological alterations in the lung tissue and to investigate the ameliorative effects of bone marrow-derived mesenchymal stem cells (BMSCs) with or without hypoxia pre-treatment. Forty-two adult male albino rats were divided into four groups: control, ozone-exposed, normoxic BMSC-treated, and hypoxic BMSC-treated groups. Lung tissue sections were processed for light and electron microscope examination, immunohistochemical staining for caspase 3, and iNOS. Quantitative real-time PCR for IL-1α, IL-17, TNF-α, and Nrf2 mRNA gene expression were also performed. Chronic O3 exposure caused elevated inflammatory cytokines and decreased antioxidant Nrf2 mRNA expression. Marked morphological alterations with increased collagen deposition and elevated apoptotic markers and iNOS were evident. BMSC treatment showed immunomodulatory (decreased inflammatory cytokine gene expression), antioxidant (increased Nrf2 expression and decreased iNOS), and anti-apoptotic (decreased caspase3 expression) effects. Consequently, ameliorated lung morphology with diminished collagen deposition was observed. Hypoxia pretreatment enhanced BMSC survival by MTT assay. It also augmented the previously mentioned effects of BMSCs on the lung tissue as proved by statistical analysis. Lung morphology was similar to that of control group. In conclusion, hypoxia pretreatment represents a valuable intervention to enhance the effects of MSCs on chronic lung injury.

Evaluation of the cardioprotective effect of Casuarina suberosa extract in rats.

The aim of the current study was to examine and compare the cardioprotective activities of the chloroform and petroleum extracts the leaves of Casuarina suberosa in isoproterenol (ISO)-induced cardiac tissue oxidative stress. Rats were categorized into 6 groups as follows: control group, vehicle or Tween 80-treated group, ISO-treated group, chloroform extract + ISO treated group, petroleum ether extract + ISO treated group and Reference drug (Captopril) + ISO treated group. ISO injection significantly (p < 0.05) increased the activities of cardiac marker enzymes (CK-MB, LDH, ALT, and AST), cardiac troponin-I, levels of lipid peroxides (MDA), nitric oxide (NO), and vascular endothelial growth factor (VEGF), serum angiotensin-converting enzyme (ACE) activity and neutrophil infiltration marker; myeloperoxidase (MPO) in the cardiac tissues. Pretreatment with chloroform or petroleum ether extracts significantly (p < 0.05) prevented the ISO-induced alteration; they upregulated VEGF expression. Histopathological findings corroborated biochemical results. These extracts exerted a cardioprotective effect by alleviating oxidative stress.

Antidiabetic and hypolipidemic potentials of Solidago virgaurea extract in alloxan-induced diabetes type 1.

OBJECTIVES: The aim of the current study is to investigate the antidiabetic and hypolipidemic potentials of Solidago virgaurea extract in alloxan-induced diabetic rats. MATERIALS AND METHODS: Alloxan-induced diabetic rats were orally administered a dose of Solidago virgaurea extract (250 mg/kg body weight) daily for 15 days. Then blood glucose, insulin, serum lipid profile, amylase, tumour necrosis factor-α (TNF- α), and liver glycogen were determined. Besides, superoxide dismutase (SOD), catalase activities, and malondialdehyde (MDA) levels in pancreatic tissue were assessed. RESULTS: Solidago virgaurea extract significantly reduced blood glucose level, serum amylase activity, TNF-α level, and pancreatic MDA level as well as increasing the serum insulin, liver glycogen level, pancreatic SOD, and catalase activities in comparison with their corresponding diabetic rats, p < .05. CONCLUSION: The findings of this study support the ethnomedicinal use of Solidago virgaurea extract as an antidiabetic and antihyperlipidemic in the management of diabetes mellitus.

Assessing anxiety and depression in cancer patients.

BACKGROUND: empirical evidence suggests that anxiety and depression in cancer patients is underdiagnosed and subsequently this patient population receives little or no support or intervention to address their psychosocial needs. It is often difficult to distinguish between normal emotional distress experienced following a cancer diagnosis and anxiety and depression, which can have a significant impact on coping mechanisms and subsequent outcomes. AIM: a qualitative study using the Hospital Anxiety and Depression Scale (HADS) was undertaken in the National Centre for Cancer Care and Research in Qatar. The driver for change was to provide evidence of the need for an assessment to be incorporated into the nursing admission process as a means of early detection and onward referral for more formal interventions if required. The sample size was 57. FINDINGS: the evidence from the outcome data supported the hypothesis that anxiety and depression were present in a significant number of the sample group. This would support the proposal of early screening and onward referral. A number of patients surveyed expressed moderate to severe depression, which may impact negatively on outcomes. CONCLUSION: screening for anxiety and depression in adult cancer patients should form part of an early nursing assessment to identify those who may benefit from more structured interventions. HADS is a useful screening tool; however, further research is required on validating tools used to screen for anxiety and depression in cancer and chronic disease in different cultures to ensure validity and reliability of outcome data.

Effect of mesenchymal stem cells on induced skeletal muscle chemodenervation atrophy in adult male albino rats.

The present research was conducted to evaluate the effect of bone marrow derived mesenchymal stem cells (BM-MSCs) as a potential therapeutic tool for improvement of skeletal muscle recovery after induced chemodenervation atrophy by repeated local injection of botulinum toxin-A in the right tibialis anterior muscle of adult male albino rats. Forty five adult Wistar male albino rats were classified into control and experimental groups. Experimental group was further subdivided into 3 equal subgroups; induced atrophy, BM-MSCs treated and recovery groups. Biochemical analysis of serum LDH, CK and Real-time PCR for Bcl-2, caspase 3 and caspase 9 was measured. Skeletal muscle sections were stained with H and E, Mallory trichrome, and Immunohistochemical reaction for Bax and CD34. Improvement in the skeletal muscle histological structure was noticed in BM-MSCs treated group, however, in the recovery group, some sections showed apparent transverse striations and others still affected. Immunohistochemical reaction of Bax protein showed strong positive immunoreaction in the cytoplasm of muscle fibers in the induced atrophy group. BM-MSCs treated group showed weak positive reaction while the recovery group showed moderate reaction in the cytoplasm of muscle fibers. Immunohistochemical reaction for CD34 revealed occasional positive CD34 stained cells in the induced atrophy group. In BM-MSCs treated group, multiple positive CD34 stained cells were detected. However, recovery group showed some positive CD34 stained cells at the periphery of the muscle fibers. Marked improvement in the regenerative capacity of skeletal muscles after BM-MSCs therapy. Hence, stem cell therapy provides a new hope for patients suffering from myopathies and severe injuries.

Lead exposure and its association with pubertal development in school-age Egyptian children: pilot study.

BACKGROUND: The aim of the present study was to determine blood lead levels in a group of Egyptian school-age children and assess its relationship to pubertal development. METHODS: Forty-one children were recruited from high- and low-pollution areas in Cairo, Egypt. Sexual maturation was evaluated using Tanner score. Measurements of blood lead and serum levels of follicle stimulation hormone (FSH), luteinizing hormone (LH), estradiol in girls and testosterone in boys were performed for included subjects. RESULTS: A total of 51.2% of children had high blood lead levels (>or=10 microg/dL). Boys with high lead levels had delayed pubertal maturation compared to those with low lead levels. Breast staging of sexual maturation was significantly delayed in girls with high lead levels. FSH and LH were significantly reduced in children of both sexes, and testosterone levels were reduced in boys with high lead. CONCLUSION: These findings consolidate the cumulative medical evidence of the deleterious effect of high lead levels on pubertal development, possibly through the hypothalamic-pituitary-gonadal axis.