Comparative evaluation of the effects of deferiprone and/or resveratrol in alleviating iron overload-induced tongue injury in rats.

Iron overload causes excessive iron deposition in extrahepatic organs, including the tongue. This study aims to compare the deferiprone and/or resveratrol treatments for the alleviation of iron overload-induced tongue injury in rats. Rats were divided into 6 groups: control group, iron-overloaded group, recovery group where rats were left to recover from iron overload, deferiprone-treated group, resveratrol-treated group, and combined deferiprone/resveratrol-treated group. Iron was administered for 4 weeks, while all treatment options were given for the subsequent 4 weeks. After 8 weeks, all rats were sacrificed; the serum iron profile was estimated, and the tongues were assessed by histopathological, tumour necrosis factor alpha (TNF-α) immunohistochemical, histomorphometric, and ultrastructural evaluations. Serum iron parameters were significantly increased in iron-overloaded rats and decreased to control levels only in the combined group. The iron-overloaded tongues demonstrated lost lingual papillae, coarse keratohyalin granules, vacuolated epithelial cells, degenerated muscle fibers, and congested blood vessels. Compared to the control rats, this group revealed a significant decrease in the epithelial layer thickness (550.7 vs. 763.4 µm), papillae height (441.4 vs. 849.7 µm), and myofiber diameter (58.5 vs. 98.6 µm), and increased lamina propria thickness (305.1 vs. 176.8 µm), fibrosis index (33.4 vs. 8.6 %), and TNF-α immunoexpression (1.16 vs. 0.63 optical density). Additionally, the ultrastructure showed hyperkeratinized papillae, wide interpapillary spaces, flat fungiform papillae, and lost gustatory pores. All these parameters were improved in the recovery, deferiprone, and resveratrol groups to different degrees, while the combined deferiprone/resveratrol treatment was the best option.

Assessment of therapeutic efficacy of adipose tissue-derived mesenchymal stem cells administration in hyperlipidemia-induced aortic atherosclerosis in adult male albino rats.

Atherosclerosis (AS) is a common disease seriously detrimental to human health. AS is a chronic progressive disease related to inflammatory reactions. The present study aimed to characterize and evaluate the effects of adipose tissue stem cells (ADSCs) in high-fat diet-induced atherosclerosis in a rat model. The present study comprises thirty-six rats and they were divided into three groups: the control group, the high-fat diet (HFD) group; which received a high-fat diet, and the high-fat diet + stem cells (HFD+SC) group; which was fed with a high-fat diet along with the administration of intravenous ADSCs. Food was given to the animals for 20 weeks to establish dyslipidemia models. After 20 weeks, animals were sacrificed by cervical dislocation; blood was collected to measure total cholesterol (TC), triglycerides (TG), low-density lipoprotein (LDL), and high-density lipoprotein (HDL); aortae were collected to detect morphologic changes. Rats of the HFD group showed a significant increase in body weight (B.Wt), altered lipid profile increased expression of inducible nitric oxide synthase (iNOS), and decreased expression of endothelial nitric oxide synthase (eNOS). However, in HFD+SC there was a significant decrease in body weight gain and an improvement in lipid profile. Histopathological and ultrastructural variations observed in the aorta of the HFD group when treated with ADSCs showed preserved normal histological architecture and reduced atherosclerosis compared with the HFD group. This was evidenced by laboratory, histological, immunohistochemical, and morphometric studies. Thus, ADSCs reduced TC, TG, and LDL, reduced the expression of iNOS, and increased the expression of eNOS. The high-fat diet was likely to cause damage to the wall of blood vessels. Systemically transplanted ADSCs could home to the aorta, and further protect the aorta from HFD-induced damage.

Impact of Ramadan fasting on vision and headache-related quality of life in women with idiopathic intracranial hypertension: A prospective observational study.

BACKGROUND: Ramadan fasting is an obligatory religious practice for Muslims. However, research data on the effect of Ramadan on idiopathic intracranial hypertension (IIH) symptoms are lacking. This study aimed to study the effect of Ramadan fasting on the severity of headache and visual symptoms and related quality-of-life activities. METHODS: This prospective cohort study targeted females diagnosed with IIH (n = 102) who were eligible to fast for Ramadan in 2023. The patients were recruited from the Neurology Clinic in Beni-Suef University Hospital, Egypt. Body mass index (BMI), monthly headache days and intensity of headache attacks, six-item Headache Impact Test (HIT-6), and the 25-item National Eye Institute Visual Function Questionnaire (NEI-VFQ-25) scores during Ramadan were compared to those during the (non-fasting) month of Shaaban, the preceding month to Ramadan. RESULTS: There was a significant increase in the BMI of patients with IIH in Ramadan compared to the (non-fasting) month of Shaaban, at a median (interquartile range [IQR]) of 30.5 (26.6-35.8) kg/m2 and 30.1 (26.6-35.2) kg/m2, respectively (p = 0.002). The median (IQR) value of monthly headache days was significantly increased during Ramadan in comparison to the (non-fasting) month of Shaaban, at 20 (11.5-30) vs. 15 (10-25) (p < 0.001). There was a statistically significant worsening in the visual analog scale (VAS) scores (median [IQR] 7 [5-8] vs. 6.5 [5-8]), HIT-6 scores (median [IQR] 61 [58-67] vs. 59 [53-61.5]), and NEI-VFQ-25 total scores (median [IQR] 1312.5 [1238.8-1435] vs 1290 [1165-1417.5]) during Ramadan in comparison to the (non-fasting) month of Shaaban (p < 0.001 for all comparisons). The change in BMI in Ramadan was positively correlated with the change in monthly headache days (r = 0.24, p = 0.014), VAS (r = 0.20, p = 0.043), HIT-6 (r = 0.25, p = 0.010) and NEI-VFQ-25 scores (r = 0.24, p = 0.016). CONCLUSION: Ramadan fasting had an aggravating effect on headache, visual symptoms, and related quality-of-life activities, which might be attributed to weight gain during this month. Whether proper nutritional management to prevent weight gain during Ramadan may help mitigate this worsening effect is a mission of future studies.

The Rho guanine dissociation inhibitor α inhibits skeletal muscle Rac1 activity and insulin action.

The molecular events governing skeletal muscle glucose uptake have pharmacological potential for managing insulin resistance in conditions such as obesity, diabetes, and cancer. With no current pharmacological treatments to target skeletal muscle insulin sensitivity, there is an unmet need to identify the molecular mechanisms that control insulin sensitivity in skeletal muscle. Here, the Rho guanine dissociation inhibitor α (RhoGDIα) is identified as a point of control in the regulation of insulin sensitivity. In skeletal muscle cells, RhoGDIα interacted with, and thereby inhibited, the Rho GTPase Rac1. In response to insulin, RhoGDIα was phosphorylated at S101 and Rac1 dissociated from RhoGDIα to facilitate skeletal muscle GLUT4 translocation. Accordingly, siRNA-mediated RhoGDIα depletion increased Rac1 activity and elevated GLUT4 translocation. Consistent with RhoGDIα's inhibitory effect, rAAV-mediated RhoGDIα overexpression in mouse muscle decreased insulin-stimulated glucose uptake and was detrimental to whole-body glucose tolerance. Aligning with RhoGDIα's negative role in insulin sensitivity, RhoGDIα protein content was elevated in skeletal muscle from insulin-resistant patients with type 2 diabetes. These data identify RhoGDIα as a clinically relevant controller of skeletal muscle insulin sensitivity and whole-body glucose homeostasis, mechanistically by modulating Rac1 activity.

Outcomes of resective surgery in pediatric patients with drug-resistant epilepsy: A single-center study from the Eastern Mediterranean Region.

OBJECTIVE: Epilepsy surgery is widely accepted as an effective therapeutic option for carefully selected patients with drug-resistant epilepsy (DRE). There is limited data on the outcome of epilepsy surgery, especially in pediatric patients from the Eastern Mediterranean region. Hence, we performed a retrospective study examining the outcomes of resective surgery in 53 pediatric patients with focal DRE. METHODS: Patients with focal DRE who had undergone epilepsy surgery were included in the present study. All patients underwent a comprehensive presurgical evaluation. Postoperative seizure outcomes were classified using the Engel Epilepsy Surgery Outcome Scale. RESULTS: After surgery, 33 patients (62.2%) were Class I according to the Engel classification of surgical outcomes; eight patients (15.0%) were Class II, 11 (20.7%) were Class III, and one (1.8%) was Class IV. The relationships of presurgical, surgical, and postsurgical clinical variables to seizure outcomes were compared. Older age at seizure onset, older age at the time of surgery, the presence of focal to bilateral tonic-clonic seizures, seizure duration over 2 minutes, unsuccessful treatment with three or fewer antiseizure medications, lesions confined to one lobe (as demonstrated via magnetic resonance imaging [MRI]), surgical site in the temporal lobe, and histopathology including developmental tumors were significantly linked to an Engel Class I outcome. A univariate analysis of excellent surgical outcomes showed that lateralized semiology, localized interictal and ictal electroencephalogram (EEG) discharges, lateralized single-photon emission computed tomography and positron emission tomography findings, and temporal lobe resections were significantly related to excellent seizure outcomes. SIGNIFICANCE: The results of our study are encouraging and similar to those found in other centers around the world. Epilepsy surgery remains an underutilized treatment for children with DRE and should be offered early.

Adenosine monophosphate-activated protein kinase is elevated in human cachectic muscle and prevents cancer-induced metabolic dysfunction in mice.

BACKGROUND: Metabolic dysfunction and cachexia are associated with poor cancer prognosis. With no pharmacological treatments, it is crucial to define the molecular mechanisms causing cancer-induced metabolic dysfunction and cachexia. Adenosine monophosphate-activated protein kinase (AMPK) connects metabolic and muscle mass regulation. As AMPK could be a potential treatment target, it is important to determine the function for AMPK in cancer-associated metabolic dysfunction and cachexia. We therefore established AMPK's roles in cancer-associated metabolic dysfunction, insulin resistance and cachexia. METHODS: In vastus lateralis muscle biopsies from n = 26 patients with non-small cell lung cancer (NSCLC), AMPK signalling and protein content were examined by immunoblotting. To determine the role of muscle AMPK, male mice overexpressing a dominant-negative AMPKα2 (kinase-dead [KiDe]) specifically in striated muscle were inoculated with Lewis lung carcinoma (LLC) cells (wild type [WT]: n = 27, WT + LLC: n = 34, mAMPK-KiDe: n = 23, mAMPK-KiDe + LLC: n = 38). Moreover, male LLC-tumour-bearing mice were treated with (n = 10)/without (n = 9) 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR) to activate AMPK for 13 days. Littermate mice were used as controls. Metabolic phenotyping of mice was performed via indirect calorimetry, body composition analyses, glucose and insulin tolerance tests, tissue-specific 2-[3H]deoxy-d-glucose (2-DG) uptake and immunoblotting. RESULTS: Patients with NSCLC presented increased muscle protein content of AMPK subunits α1, α2, ß2, γ1 and γ3 ranging from +27% to +79% compared with control subjects. In patients with NSCLC, AMPK subunit protein content correlated with weight loss (α1, α2, ß2 and γ1), fat-free mass (α1, ß2 and γ1) and fat mass (α1 and γ1). Tumour-bearing mAMPK-KiDe mice presented increased fat loss and glucose and insulin intolerance. LLC in mAMPK-KiDe mice displayed lower insulin-stimulated 2-DG uptake in skeletal muscle (quadriceps: -35%, soleus: -49%, extensor digitorum longus: -48%) and the heart (-29%) than that in non-tumour-bearing mice. In skeletal muscle, mAMPK-KiDe abrogated the tumour-induced increase in insulin-stimulated TBC1D4thr642 phosphorylation. The protein content of TBC1D4 (+26%), pyruvate dehydrogenase (PDH; +94%), PDH kinases (+45% to +100%) and glycogen synthase (+48%) was increased in skeletal muscle of tumour-bearing mice in an AMPK-dependent manner. Lastly, chronic AICAR treatment elevated hexokinase II protein content and normalized phosphorylation of p70S6Kthr389 (mTORC1 substrate) and ACCser212 (AMPK substrate) and rescued cancer-induced insulin intolerance. CONCLUSIONS: Protein contents of AMPK subunits were upregulated in skeletal muscle of patients with NSCLC. AMPK activation seemed protectively inferred by AMPK-deficient mice developing metabolic dysfunction in response to cancer, including AMPK-dependent regulation of multiple proteins crucial for glucose metabolism. These observations highlight the potential for targeting AMPK to counter cancer-associated metabolic dysfunction and possibly cachexia.

Detection of unusual Cryptosporidium parvum subtype in patients with gastrointestinal cancer in Egypt.

While the importance of cryptosporidiosis in immunocompromised persons is well known, the prevalence of Cryptosporidium spp. in cancer patients is not clear. The current study was designed to assess the occurrence and genetic characteristics of Cryptosporidium spp. in patients with gastrointestinal (GI) cancer in Egypt. Stool samples were collected from 100 patients with GI malignancies and 20 healthy individuals without any GI manifestations (control group). They were screened by microscopy and the immunochromatographic RIDA®QUICK Cryptosporidium kit. Subtyping of Cryptosporidium spp. was conducted by sequence analysis of the glycoprotein 60 (gp60) locus. Sociodemographic, environmental data and information on GI symptoms, cancer types, and clinical treatment were obtained via a questionnaire. By microscopy and RIDA®QUICK, only 7% (7/100) of GI cancer patients were positive for Cryptosporidium, compared with 40% (40/100) by gp60 nPCR. No positives were obtained from the control group. Male sex (P = 0.02) and younger age (P = 0.004) were major Cryptosporidium risk factors for infection. The occurrence of Cryptosporidium was also significantly more frequent (P = 0.003) in watery stool samples. Sequence analysis of the gp60 amplicons (~ 400 bp) identified a novel C. parvum subtype with nine TCA repeats and eleven ACATCA repeats. A formal subtype designation could not be made due to the short sequence length. More studies should be conducted to verify the common occurrence of this unusual C. parvum subtype and establish its genetic identity.

Expression of GLUT4 and FAP in urothelial bladder carcinoma: correlation with angiogenesis and clinicopathological characteristics.

BACKGROUND: Urothelial carcinoma (UC) is the most common type of bladder cancer. Glucose transporter 4 (GLUT4) is one of glucose transporter proteins' family which facilitates glucose transport inside the cells. It was found to be overexpressed in several malignant tumors. Cancer-associated fibroblasts (CAFs) are heterogeneous stromal cells located adjacent to cancer cells and are considered one of the most important tumor stromal cells. They have been associated with enhancing tumor growth and invasion. GLUT4 expression in malignant epithelial cells and fibroblast activation protein (FAP) expression in CAFs of UC in relation to angiogenesis and clinicopathological characteristics are studied in this work. MATERIALS AND METHODS: The study was carried out on 72 paraffin blocks of UC (27 radical cystectomies and 45 transurethral resections). Immunohistochemical staining was performed with GLUT4, FAP, and CD34 antibodies. Expression of GLUT4 and FAP was classified according to the staining intensities and percentages into low and high groups. CD34-stained microvessels' mean count in five microscopic fields (×200) was taken as the microvessel density (MVD). RESULTS: GLUT4 overexpression was detected in 32 UC. It was significantly associated with high-grade tumors, advanced primary tumor (pT) stage, lymphovascular invasion (LVI), and regional lymph node invasion. High FAP expression was appreciated in 27 UC and was significantly linked to LVI and advanced TNM staging. Intratumor MVD significantly increased in UC with muscle invasion, LVI, and regional lymph node and/or distant metastasis. A significant positive correlation between GLUT4, FAP expression, and MVD was found. CONCLUSION: GLUT4 and FAP expression was significantly associated with increased intratumor MVD and adverse clinicopathological factors.

Epilepsy in patients with WWOX-related epileptic encephalopathy (WOREE) syndrome

Objective: Epileptic encephalopathy (EE) is difficult to diagnose and manage. It can be caused by a variety of disorders, and its aetiology may guide management and prognosis. The human gene for WW domain-containing oxidoreductase (WWOX) has been associated with epileptic encephalopathy, which presents in infancy with seizures, psychomotor delay, microcephaly, and optic atrophy. Methods: We report nine patients with WWOX-related EE from six families. We provide detailed descriptions of clinical presentations, imaging findings, neurophysiological manifestations, and related mutations. Whole-exome sequencing (WES) was used to identify the mutations in the WWOX gene. Results: We established correlations between genotype and phenotype in our cases and previously reported cases. Significance: Our data support previously reported findings regarding WWOX-related EE, indicating the importance of the human WWOX gene in brain development and the association between WWOX mutations and EE. Our study also highlights the power of WES, particularly in clinically challenging cases.

Assessment of the efficacy of thymol against Toxocara vitulorum in experimentally infected rats.

The effect of thymol and ivermectin on the development and embryonation of Toxocara vitulorum (T. vitulorum) eggs, as well as their migration in albino rats was investigated both in vitro and in vivo. A total of forty male albino rats were divided into four groups for an in vivo experiment. The first group was uninfected; the second group was infected but left untreated; the third group was infected and received thymol at a dose of 40 mg/kg; and the fourth group was infected and received ivermectin (0.2 mg/kg). In vitro, thymol inhibited the development of Toxocara larvae within the eggs. However, ivermectin, produced inconsistent results. The in vivo results indicated that the recovery rates of Toxocara larvae from the liver and lungs on day 7 post-infection were significantly lower in the thymol or ivermectin-treated groups than in the infected untreated control. Albumin levels were significantly increased in the thymol-treated group as compared to the positive control and ivermectin groups. Nitric oxide, IL-4, and IFN- levels in the serum of the thymol or ivermectin-treated groups were significantly lower than that of the positive control group. Histopathological examination demonstrated that thymol and ivermectin were effective in reducing larval load, reducing the number and size of granulomas in the absence of larvae, and improving tissue architecture. The current study concluded that thymol possessed anti-Toxocara activity in a rat model. Additionally, thymol possessed ovicidal properties and may be used as a disinfectant.

miR-370 is better than miR-375 as a non-invasive diagnostic biomarker for pediatric acute myeloid leukemia patients.

BACKGROUND: Acute myeloid leukemia (AML) is characterized by heterogeneity in phenotypic, genotypic, and clinical traits. miRNAs play an important role in pathogenesis and diagnosis of adult AML. Such information is not available about miRNA expression role in pediatric AML. OBJECTIVE: We aimed to investigate the expression of miR-370 and miR-375 as new diagnostic biomarkers to discriminate pediatric AML patients and to predict their roles in the disease molecular basis. METHODS: The expression of both miR-370 and miR-375 in peripheral blood (PB) of pediatric AML patients was assessed by QPCR; their impact for diagnosis was evaluated by ROC curve and their roles in pediatric AML development were predicted by bioinformatics analysis. RESULTS: The expression of miR-370 and miR-375 levels was significantly decreased in pediatric AML patients, suggesting them as tumor suppressor miRNAs as supported by bioinformatics analysis. miR-370 showed better potential and sensitivity toscreen pediatric AML patients and more significant correlation with AML risk than miR-375. This is the first study to report the positive correlation between both miR-370 and miR-375. CONCLUSION: miR-370 level in peripheral blood can serve as a potential non-invasive diagnostic biomarker and was significantly correlated with AML risk. We strongly recommend PB miRNAs as diagnostic biomarkers for pediatric AML.

Efficacy and Safety of Topical Silymarin Versus Low Fluence 1064-nm Q Switched Nd:YAG Laser in the Treatment of Melasma: A Comparative Randomized Trial.

BACKGROUND AND OBJECTIVES: The management of melasma is challenging and requires multiple uses of available therapeutic options. To compare the short-term efficacy and safety of topical silymarin and low fluence 1064-nm Q-switched ND:YAG laser for treatment of melasma with dermoscopic follow-up. STUDY DESIGN/MATERIALS AND METHODS: Fifty female patients with melasma were included in this study. They were randomly divided into two groups. Group A: 25 patients were treated with six sessions of low fluence Q switched ND:YAG 1064-nm laser, and group B: 25 patients were treated with topical silymarin cream 1.4% with a 3-month treatment duration. Patients were evaluated clinically by the modified melasma area and severity index (mMASI) score. Dermoscopic examinations were performed before and after the treatment sessions. RESULTS: The severity of melasma, as evaluated dermoscopically and clinically by mMASI score, was significantly reduced after treatment in all patients with no recorded side effects. There was no statistically significant difference between both studied groups regarding the change in mMASI score and dermoscopic assessment of the patients after the treatment sessions. CONCLUSION: Both low fluence Q switched ND:YAG 1064-nm laser and topical silymarin cream appear to be safe and effective modalities in the treatment of melasma. © 2021 Wiley Periodicals LLC.

Serotonin-release assay-positive but platelet factor 4-dependent enzyme-immunoassay negative: HIT or not HIT?

IgG-specific and polyspecific PF4-dependent enzyme-immunoassays (EIAs) have exceptionally high sensitivity (≥99%) for diagnosis of heparin-induced thrombocytopenia (HIT), a drug reaction caused by platelet-activating antibodies detectable by serotonin-release assay (SRA). The IgG-specific EIAs are recommended for screening, as their high sensitivity is accompanied by relatively high specificity vis-à-vis polyspecific EIAs. We investigated the frequency of SRA-positive/EIA-negative (SRA+/EIA-) HIT, prompted by referral to our reference HIT laboratory of serial blood samples from a patient ("index case") with false-negative IgG-specific EIAs. Despite initial clinical suspicion for HIT, repeat negative IgG-specific EIAs prompted heparin resumption, which triggered recurrent thrombocytopenia and near-fatal cardiac arrest, indicating likely post-heparin HIT-associated anaphylactoid reaction. Further investigations revealed a strong-positive SRA, whether performed with heparin alone, PF4 alone, or PF4/heparin, with inhibition by Fc receptor-blocking monoclonal antibody (indicating IgG-mediated platelet activation); however, five different IgG-specific immunoassays yielded primarily negative (or weak-positive) results. To investigate the frequency of SRA+/EIA- HIT, we reviewed the laboratory and clinical features of patients with this serological profile during a 6-year period in which our reference laboratory investigated for HIT using both SRA and IgG-specific EIA. Although ~0.2% of 8546 patients had an SRA+/EIA- profile, further review of 15 such cases indicated clerical/laboratory misclassification or false-positive SRA in all, with no SRA+/EIA- HIT case identified. We conclude that while SRA+/EIA- HIT is possible-as shown by our index case-this clinical picture is exceptionally uncommon. Moreover, the requirement for a positive EIA is a useful quality control maneuver that reduces risk of reporting a false-positive SRA result.

Cancer causes metabolic perturbations associated with reduced insulin-stimulated glucose uptake in peripheral tissues and impaired muscle microvascular perfusion.

BACKGROUND: Redirecting glucose from skeletal muscle and adipose tissue, likely benefits the tumor's energy demand to support tumor growth, as cancer patients with type 2 diabetes have 30% increased mortality rates. The aim of this study was to elucidate tissue-specific contributions and molecular mechanisms underlying cancer-induced metabolic perturbations. METHODS: Glucose uptake in skeletal muscle and white adipose tissue (WAT), as well as hepatic glucose production, were determined in control and Lewis lung carcinoma (LLC) tumor-bearing C57BL/6 mice using isotopic tracers. Skeletal muscle microvascular perfusion was analyzed via a real-time contrast-enhanced ultrasound technique. Finally, the role of fatty acid turnover on glycemic control was determined by treating tumor-bearing insulin-resistant mice with nicotinic acid or etomoxir. RESULTS: LLC tumor-bearing mice displayed reduced insulin-induced blood-glucose-lowering and glucose intolerance, which was restored by etomoxir or nicotinic acid. Insulin-stimulated glucose uptake was 30-40% reduced in skeletal muscle and WAT of mice carrying large tumors. Despite compromised glucose uptake, tumor-bearing mice displayed upregulated insulin-stimulated phosphorylation of TBC1D4Thr642 (+18%), AKTSer474 (+65%), and AKTThr309 (+86%) in muscle. Insulin caused a 70% increase in muscle microvascular perfusion in control mice, which was abolished in tumor-bearing mice. Additionally, tumor-bearing mice displayed increased (+45%) basal (not insulin-stimulated) hepatic glucose production. CONCLUSIONS: Cancer can result in marked perturbations on at least six metabolically essential functions; i) insulin's blood-glucose-lowering effect, ii) glucose tolerance, iii) skeletal muscle and WAT insulin-stimulated glucose uptake, iv) intramyocellular insulin signaling, v) muscle microvascular perfusion, and vi) basal hepatic glucose production in mice. The mechanism causing cancer-induced insulin resistance may relate to fatty acid metabolism.

Toxoplasma gondii in cancer patients receiving chemotherapy: seroprevalence and interferon gamma level.

Toxoplasma gondii is an opportunistic parasite causing life-threatening diseases in immune-compromised patients. The purpose of the study is to determine the seroprevalence of Toxoplasma gondii in chemotherapy receiving cancer patients in relation to different types of malignancies, and to estimate the level of interferon gamma in Toxoplasma seropositive and seronegative cancer patients and healthy controls. Anti-Toxoplasma IgG and IgM antibodies, and interferon gamma were analyzed in 120 cancer patients receiving chemotherapy (60 having hematological malignancies and 60 with solid organ tumors) and 60 healthy controls using ELISA method. Toxoplasma (IgG and IgM) were determined in (66.7% and 9.2%) of the cancer group compared to (33.3% and 6.7%) of the control group with statistical significance only in IgG seropositivity (p < 0.001, OR = 4). Patients with hematological malignancies had higher IgG seropositivity than solid organ tumors (40% vs 26.7%). The difference between the groups was statistically significant (p = 0.002, OR = 3.5). Median level of interferon gamma was in the same range between cancer patients and control group. However, it was highly elevated in Toxoplasma seropositive (76 pg/ml) than seronegative (44.5 pg/ml) cases with statistical significance (p < 0.001). T. gondii infection remains a major threat to cancer patients and still needs proper screening, diagnosis and treatment.

Harderian gland-derived stem cells as a cytotherapy in a guinea pig model of carboplatin-induced hearing loss.

BACKGROUND: Stem cells therapy of hearing loss is a challenging field due to lacking self-regenerative capacity of cochlea. Harderian gland of guinea pigs was thought to harbour a unique type of progenitors which could restore the damaged cochlear tissues. THE AIM: of this study was to isolate Harderian gland derived stem cells (HG-SCs) and investigate their efficacy in restoring the damaged cochlear tissue in carboplatin-induced hearing loss. METHODOLOGY: Sixty female and 10 male pigmented guinea pigs were used; the male animals were HG-SCs donors, while the females were assigned into 3 groups; control, hearing loss (HL) and HG-SC-treated groups. Auditory reflexes were assessed throughout the study. The animals were euthanized 35 days after HG-SCs transplantation, the cochleae were extracted and processed for assessment by light microscope and scanning electron microscope. Morphometric assessment of stria vascularis thickness, hair cells and spiral ganglia neuronal number and optical density of TLR4 expression were done. RESULTS: The isolated HG-SCs had the same morphological and phenotypical character as mesenchymal stem cells. HL group revealed destruction of organ of Corti, stria vascularis and spiral ganglion with decreased morphometric parameters. Restoration of both cochlear structure and function was observed in HG-SC-treated group along with a significant increase in IHCs, OHCs numbers, stria vascularis thickness and spiral ganglionic cell count to be close to the values of control group. CONCLUSION: The isolated HG-SCs were proved to restore structure and function of cochlea in guinea pig model of hearing loss.

Role of bone marrow derived mesenchymal stromal cells and Schwann-like cells transplantation on spinal cord injury in adult male albino rats.

BACKGROUND: Spinal cord injury is a considerable health impact accompanied with physical, psychological and economic burden. Bone marrow derived mesenchymal stromal cells (BM-MSCs) transplantation was found to produce neuronal regenerative effects. Schwann-like cells differentiated from BM-MSCs have myelin-forming ability. AIM OF THE WORK: To compare the ability of BM-MSCs versus Schwann like cells to promote recovery of spinal cord injury. MATERIAL AND METHODS: Adult male albino rats were used throughout the study. BM-MSCs were harvested from femora of rats. Sciatic nerves were extracted and used in the preparation of the induction culture medium for differentiation of BM-MSCs into Schwann-like cells. Rats were divided into control, spinal cord injured (SCI), spinal cord injured plus BM-MSCs transplantation (BM-MSC) and spinal cord injured plus Schwann-like cells transplantation (Sn) groups. BBB scale assessment was performed before and after SCI in all rats. Rats were euthanized at the end of the 7th week and spinal cords were dissected and processed for light and transmission electron microscopic examinations. RESULTS: Spinal cord sections of SCI group revealed cavitation, necrosis and demyelination. BM-MSC and Sn groups showed both functional and structural improvement compared to SCI group with better BBB score and histopathological features in the BM-MSC group and more expression of S100 in the Sn group. CONCLUSION: Transplantation of BM-MSCs and Schwann-like cells improved the structural and functional alterations of spinal cord injury with better improvement in BM-MSC group.

Therapeutic efficacy of olfactory stem cells in rotenone induced Parkinsonism in adult male albino rats.

BACKGROUND: Olfactory stem cells (OSCs) are found in the olfactory mucosa and olfactory bulb and have the capacity to proliferate and differentiate along multiple tissue lineages. Rotenone; widely used insecticide has a neurodegenerative effect on the dopaminergic cells of substantia nigra (SN) of midbrain producing Parkinsonism. The aim of this study is to isolate rat OSCs from olfactory mucosa and olfactory bulb, culture these OSCs in suitable medium to allow for their proliferation to be used in the treatment of Parkinsonism induced by rotenone. METHODS: The characteristics of OSCs, the effects of rotenone on the SN of midbrain and the curative effect of OSCs on the substantia nigra were determined morphologically, immunohistochemically, and by transmission electron microscopy. PKH 26; immunofluorescent dye was used as a cell tracer to locate the transplanted cells in host midbrain. RESULTS: OSCs were spindle shaped with irregular processes, and were positive for CD44 and Nestin and negative for CD34. Subcutaneous rotenone produced Parkinsonism through producing degeneration of the dopaminergic cells of SN of the midbrain. Transplantation of OSCs produced restoration of the normal structure of SN and dopaminergic cells and improves the clinical manifestations of Parkinsonism. CONCLUSION: These results indicate that, the isolated rat OSCs can proliferate and expand in vitro when culture in suitable medium and these cells can exert therapeutic effects in Parkinsonism by recruitment in SN and restoration of the structure and function of dopaminergic cells.

Rac1 muscle knockout exacerbates the detrimental effect of high-fat diet on insulin-stimulated muscle glucose uptake independently of Akt.

KEY POINTS: The actin cytoskeleton regulating GTPase, Rac1, is a novel player in insulin-stimulated glucose uptake in muscle in vivo. High-fat diet (HFD) exacerbates muscle insulin resistance in Rac1 muscle knockout (mKO) mice. Muscle Rac1 KO protects against HFD-induced insulin resistance in fat tissue indicating tissue cross-talk. A fatty diet markedly reduces insulin clearance in mice. ABSTRACT: Insulin resistance and perturbations in glucose metabolism underpin common lifestyle diseases such as type 2 diabetes and obesity. Insulin resistance in muscle is characterized by compromised activity of the GTPase, Ras-related C3 Botulinum toxin substrate 1 (Rac1), yet the role of Rac1 in insulin-stimulated glucose uptake in vivo and diet-induced insulin resistance is unknown. Inducible muscle-specific Rac1 knockout (Rac1 mKO) and wild type (WT) littermate mice were either fed a chow or a 60% high-fat diet (HFD). Insulin-stimulated 2-deoxy-glucose uptake, intracellular signalling, protein expression, substrate utilization, and glucose and insulin tolerance were assessed. In chow-fed mice, in vivo insulin-stimulated glucose uptake was reduced in triceps, soleus and gastrocnemius muscles from Rac1 mKO mice. HFD-induced whole body insulin resistance was exacerbated by the lack of muscle Rac1 and glucose uptake was reduced in all muscles, except for soleus. Muscle Akt (also known as protein kinase B) signalling was unaffected by diet or genotype. In adipose tissue, Rac1 mKO mice were protected from HFD-induced insulin resistance (with respect to both glucose uptake and phosphorylated-Akt), rendering their whole body glucose tolerance comparable to WT mice on HFD. Our findings show that lack of Rac1 exacerbates HFD-induced insulin resistance in skeletal muscle. Whole body glucose tolerance, however, was largely unaffected in Rac1 mKO mice, likely due to improved insulin-stimulated glucose uptake in adipose tissue. We conclude that lack of Rac1 in the context of obesity is detrimental to insulin-stimulated muscle glucose uptake in muscle independently of Akt signalling.

Thermogram breast cancer prediction approach based on Neutrosophic sets and fuzzy c-means algorithm.

The early detection of breast cancer makes many women survive. In this paper, a CAD system classifying breast cancer thermograms to normal and abnormal is proposed. This approach consists of two main phases: automatic segmentation and classification. For the former phase, an improved segmentation approach based on both Neutrosophic sets (NS) and optimized Fast Fuzzy c-mean (F-FCM) algorithm was proposed. Also, post-segmentation process was suggested to segment breast parenchyma (i.e. ROI) from thermogram images. For the classification, different kernel functions of the Support Vector Machine (SVM) were used to classify breast parenchyma into normal or abnormal cases. Using benchmark database, the proposed CAD system was evaluated based on precision, recall, and accuracy as well as a comparison with related work. The experimental results showed that our system would be a very promising step toward automatic diagnosis of breast cancer using thermograms as the accuracy reached 100%.