The role of autophagy-related gene 9B in lichen planus

Background: Lichen planus (LP) is an idiopathic, chronic, relapsing, inflammatory, autoimmune dermatological disease. The etiopathogenesis of LP is still unclear. Autophagy is a strictly regulated lysosomal degradation pathway that is crucial for maintaining intracellular homeostasis and normal development. The dysregulation of autophagy-associated genes was recognized to increase the susceptibility to multiple diseases, including inflammation, autoimmune disorders and cancer. Aims: Our study aimed to detect the expression of autophagy-related gene 9 b (ATG9B) in LP patients compared to normal control persons to investigate the possible role of autophagy in pathogenesis of this disease. Methods: This case–control study included 30 LP patients and 30 age-, gender-matched healthy controls. Four millimeters punch skin biopsies were obtained from LP lesions and from the controls and they were kept in lysis solution for the stability of the studied parameters and were kept frozen at –80°C till analysis of ATG9B using real-time polymerase chain reaction. Results: The level of ATG9B in lesional skin of LP was significantly decreased compared to normal control persons (P < 0.01); also, there was a non-significant relation between ATG9B level and age, sex, duration and family history among LP patients. Limitations: Limited number of patients included in our study (30 patients). Conclusion: Autophagy may play a role in the pathogenesis of cutaneous LP.

Thymoquinone ameliorates acute kidney injury induced by renal ischemia-reperfusion / La timoquinona mejora la lesión renal aguda inducida por isquemia-reperfusión renal

SUMMARY: Renal ischemia-reperfusion injury (IRI)is an unavoidable consequence in renal transplantation and multiple clinical settings. A debate has been raised about the particular role of hypoxia-inducible factor (HF-1α) in the renal injury pathogenesis and the renal cortex ultrastructural alterations. Also, we investigated the antioxidant/anti-inflammatory effect of thymoquinone and its modulatory role on HIF-1α in protection against renal IRI.Adult male Wister albino rats were assigned into 3 groups (n=16); 1) Sham-operated, 2) IRI model and 3) renal IRI pre-treated with thymoquinone 10 mg.kg-1.day-1 (TQ-IRI) for 10 days and at the reperfusion onset. Following the operation, 8 rats from each group were euthanized after 3 hours and the remaining 8 rats at 24 hours. Renal injury was assessed by the increased blood urea nitrogen, creatinine level, and the EGTI histological injury scoreat both 3 and 24h. HIF-1α was upregulated (p<0.01) and was correlated with renal tissue reactive oxygen species (ROS) production and total oxidant capacity (TAC) consumption. Elevated inflammatory markers (NFkB, MCP-1 and VCAM-1) were associated with renal IRI.Thymoquinone treatment inhibited the accumulation of HIF-1α (p<0.01), reduced renal oxidation/inflammation process and markedly diminished renal injury.

RESUMEN: La lesión por isquemia-reperfusión renal (IRR) es una consecuencia inevitable en el trasplante renal como también en múltiples contextos clínicos. Se ha suscitado una discusión referente a la relación particular del factor inducible por hipoxia (HF- 1α) en la patogénesis de la lesión renal y las alteraciones ultraestructurales de la corteza renal. Además, investigamos el efecto antioxidante / antiinflamatorio de la timoquinona y su papel modulador sobre HIF-1α en la protección contra IRR. Se utilizaron ratas albinas Wister macho adultas divididas en 3 grupos (n = 16); 1) Intervención simulada, 2) modelo IRR y 3) IRR pretratado con timoquinona 10 mg/kg-1. día-1 (TQ-IRR) durante 10 días y al inicio de la reperfusión. Posterior a la operación, 8 ratas de cada grupo fueron sacrificadas después de 3 horas y las 8 ratas restantes a las 24 horas. La lesión renal se evaluó por el aumento de nitrógeno ureico en sangre, el nivel de creatinina y la puntuación de lesión histológica EGTI tanto a las 3 como a las 24 horas. HIF-1α se incrementó (p <0,01) y se correlacionó con la producción de especies de oxígeno reactivo (ROS) del tejido renal y el consumo de capacidad oxidante total. Los marcadores inflamatorios elevados (NFkB, MCP-1 y VCAM-1) se asociaron con IRR. El tratamiento con timoquinona inhibió la acumulación de HIF-1α (p <0,01), redujo el proceso de oxidación / inflamación renal y disminuyó notablemente la lesión renal.

High-fat diet augments ovariectomy-induced bone resorption in rats / Dieta rica en grasas aumenta la resorción ósea inducida por ovariectomía en ratas

Menopause complications such as cardiovascular and bone diseases represent a major public health concern. We sought to determine whether a high-fat diet (HFD) can augment ovariectomy-induced bone resorption in a rat model of menopause possibly via the upregulation of the inflammatory biomarkers and dyslipidemia. Rats were either ovariectomized and fed a standard laboratory chow (model group) or were ovariectomized and fed with a HFD for 15 weeks before being sacrificed. Ovariectomy significantly (p<0.05) increased body weight, dyslipidemia, insulin resistance, pro-inflammatory cytokines tumor necrosis factor-a (TNF-α) and interleukin-6 (IL-6), and biomarker of bone resorption, nuclear factor-kB (NF-kB), which were augmented by feeding animals with a HFD. This was confirmed through immunohistochemical study, where ovariectomy induced expression of p65/NF-kB protein in tibia bone sections of the model group, which were augmented by HFD. HFD augments ovariectomy-induced bone resorption through increased inflammatory biomarkers and NF-kB in rats.

Las complicaciones de la menopausia, como las enfermedades cardiovasculares y óseas, representan un importante problema de salud pública. Intentamos determinar si una dieta alta en grasas (HFD) puede aumentar la resorción ósea inducida por ovariectomía en un modelo de menopausia en ratas, a través de la regulación positiva de los biomarcadores inflamatorios y la dislipidemia. Las ratas fueron ovariectomizadas y alimentadas con una comida estándar de laboratorio (grupo modelo) o fueron ovariectomizadas y alimentadas con un HFD durante 15 semanas antes de ser sacrificadas. La ovariectomía aumentó significativamente (p <0,05) el peso corporal, dislipidemia, resistencia a la insulina, citocinas proinflamatorias, factor de necrosis tumoral a (TNF-α) e interleucina-6 (IL-6), y el biomarcador de resorción ósea, factor nuclear-kB (NF-kB), que se aumentaron alimentando animales con un HFD. Esto se confirmó a través del estudio inmunohistoquímico, donde la ovariectomía indujo la expresión de la proteína p65 / NF-kB en secciones de hueso de tibia del grupo modelo, que fueron aumentadas por HFD. HFD aumenta la resorción ósea inducida por ovariectomía a través del aumento de biomarcadores inflamatorios y NF-kB en ratas.

Evaluation of Glucosamine Effect Against Heart and Brain Damage Induced by Y-radiation or Aluminium Chloride in Female Rats

Abstract Glucosamine is known as anti-inflammatory, antioxidant and as neuroprotective as well as using to treat many of diseases. This work aimed to investigate the remedial effect of glucosamine (20mg/kg b.wt) against the damage induced by a single dose of γ-radiation (8Gy) or aluminium chloride (AlCl3) (100mg/kg b.wt) in the heart and brain tissues of female rats. Serum aspartate aminotransferase (AST), cholesterol, triglycerides (TGs), LDH and creatine kinase (CPK) were measured. Moreover, gene expression of amyloid protein precursor (APP) and seladin-1 were estimated in the brain tissue. Also, acetylcholinesterase activity (AChE) and p-tau protein expression were estimated in brain homogenate. Metallothioneine (MT) was estimated in the heart and brain tissues. Heart and brain histopathological examination was performed. Irradiation significantly decreased serum AST, CPK and LDH, as well as MT levels in heart and brain tissues. Also, gene expression of seladin-1 decreased. On the other hand, irradiation significantly increased serum TGs level and brain AchE activity, tau protein, and β-amyloid percursor (APP). AlCl3 administration (21 days) induced disturbance in most of the estimated parameters, especially AST, TGs, and MT. Glucosamine treatment with irradiation or AlCl3 improved most of the measured parameters. In addition, histopathological examination confirmed the biochemical results. In conclusion: Glucosamine could be used to improve the heart and brain damages induced by γ-radiation exposure or AlCl3.

Pathogenic role of érythropoïétine in Egyptian systemic lupus erthymatosus anemic patients: Prevalence of different types of anemia in SLE / Papel patógeno de la eritropoyetina en pacientes egipcios anémicos con LES; prevalencia de diferentes tipos de anemia en el lupus eritematoso sistémico

Abstract Background & aim: Systemic lupus erythematosus is an autoimmune disease, its pathogenesis encompasses numerous organs. About 50% of cases of SLE are anemic; multiple pathways are attributed to the occurrence of anemia. Anemia of chronic disease is generally due to reduced erythropoietin function, reduced production and low response to erythropoietin action on red blood cells, which play a role in the development of anemia of chronic disease seen in several conditions with autoimmune etiology. There were three main contributions in our research: First: To evaluate the types of anemia associated with SLE. Second: To evaluate the role of erythropoietin in pathogenesis of SLE associated anemia. Third: To evaluate the correlation between level of anemia and erythropoietin level. Subjects & methodology: 150 patients with SLE were registered in our study. SLE activity was measured by SLE disease activity index. Results: Our study encompassed (150) SLE patients, 20 men and 130 women and (50) controls, 9 men and 41 women. Among them, anemia of chronic disease was the most prevalent (41.3%), then anemia due to iron deficiency (33.3%), and lastly anemia of autoimmune etiology (25.3%). Our study also showed that there was statistically significant dissimilarity (P value = 0.023) between all groups of anemia in erythropoietin value but there was no significant correlation between erythropoietin and hemoglobin levels in any of the three groups. Conclusion: Erythropoietin level variation was detected among the dissimilar groups of anemia but no correlation between hemoglobin level and erythropoietin was found (blunted erythropoietin response).

Resumen Antecedentes y objetivo: El lupus eritematoso sistémico (LES) es una enfermedad autoinmune, su patogénesis abarca numerosos órganos. Alrededor del 50% del lupus sistêmico es anémico; las múltiples vías se atribuyen a la aparición de anemia. La anemia por enfermedad crónica generalmente se debe a la función reducida de la eritropoyetina, la producción reducida y la baja respuesta a la acción de la eritropoyetina en los glóbulos rojos que desempeñan un papel en el desarrollo de la anemia de la enfermedad crónica observada en varias enfermedades con etiología autoinmune. Hubo 3 contribuciones principales en nuestra investigación: Primero: evaluar los tipos de anemia asociados con el lupus sistémico. Segundo: evaluar el papel de la eritropoyetina en la patogénesis de la anemia asociada al lupus sistêmico. Tercero: evaluar la correlación entre el nivel de anemia y el nivel de eritropoyetina. Sujetos y metodología: Ciento cincuenta pacientes con lupus sistémico se registraron en nuestro estudio. La actividad sistémica del lupus se calculó mediante el índice de actividad de la enfermedad del LES. Resultados: Nuestro estudio abarcó 150 pacientes con lupus sistêmico, 20 varones y 130 mujeres y 50 controles, 9 varones y 41 mujeres. Entre ellos, la anemia de la enfermedad crónica fue la más prevalente (41,3%), seguida de la anemia por deficiencia de hierro (33,3%) y, finalmente, la anemia con etiología autoinmune (25,3%). Nuestro estudio también mostró que hubo diferencias estadísticamente significativas (valor de p = 0,023) entre todos los grupos de anemia en el valor de eritropoyetina, pero no hubo una correlación significativa entre los niveles de eritropoyetina y hemoglobina en ninguno de los 3 grupos. Conclusión: Se detectó una variación en el nivel de eritropoyetina entre los diferentes grupos de anemia, pero no se encontró correlación entre el nivel de hemoglobina y la eritropoyetina (respuesta de eritropoyetina atenuada).

Bone Marrow Mesenchymal Stem Cells Regulate Coagulation and Inflammation Together in Methotrexate Induced Lung Injury Rat Model

Abstract Clinical research has shed the light on the relation between coagulation and inflammation. Coagulation cascade is activated in lung injury resulting in thrombotic and fibrotic lesions. Such a cascade is initiated by inflammation, then the two systems intense each other. New therapies that modulate coagulation and inflammation will be more successful than therapies targeting only one of them. Mesenchymal stem cells showed anti-inflammatory functions in animal models. The role of mesenchymal stem cells in methotrexate induced lung injury model was evaluated, but no studies scoped on the role of stem cells in coagulation associated with inflammation in such models. This study focuses on the therapeutic role of mesenchymal stem cells against the development of clotting in methotrexate induced lung injury rat model. Results showed that mesenchymal stem cells treatment for 4 weeks caused a decrease in lung activated coagulation factors; protease activated receptor-1, fibrinogen, plasminogen activator inhibitor-1 and platelet count with a decrease in inflammatory factors; tumor necrosis factor-α, interferon- γ, interleukin-8, monocyte chemoattractant protein-1 and total leukocyte count. Thus, mesenchymal stem cells have anti-inflammatory potency against clotting risk in methotrexate induced lung injury model. This opens the outlook for stem cells as a new therapy that moderates coagulation associated with inflammation.

Role of Vitamin D and Metformine on Pancreatic Tissue in an Experimental Model of Type II Diabetes Mellitus

Background: The study was done to evaluate the role of Vitamin D (Vit D) in an experimental model of type II DM and compare its effects with oral hypoglycemic drugs (Metformine). Methods: 30 male rats were divided; control group, Diabetic group via administration of high fat diet then injection of streptozotocin . Diabetic rats were then divided into Diabetic group, Diabetic + Metformine group(n=6), Diabetic +Vit D (n=6), Diabetic + Metformine +Vit D (n=6). Fasting glucose, insulin, HOMA IR, Cholesterol, Triglycerides, C-Reactive protein (CRP), Glucagon like peptide (GLP1), Cyclooxygenase 2 (COX2) and Superoxide dismutase (SOD) were measured, Real time PCR for pancreatic expression levels of Caspase 3, IKKβ and Western plot of Pancreatic protein kinase beta (Akt) and INGAP (islet neogensis associated protein), and histopathological, immunohistochemical for pancreatic tissue. Results: Increased glucose, fasting insulin, HOMA IR , cholesterol, triglycerides, CRP, COX2 and expression of levels of Caspase 3 and  IK Kinase B and Akt in diabetic group in comparison to control. On the other hand, significant decreased levels of GLP1, SOD and INGAP in diabetic in comparison to control. On treatment with metformine or Vitamin D improved all parameters. In combined metformine and vitamin D therapy there was much improvement with no significant change from control. Conclusions: Vitamin D and metformine improved inflammatory, oxidative stress, apoptotic conditions in an experimental model of type II DM and combined therapy causes more improvement, so it is better to give combined therapy.

Effect of Occupational Exposure to Aluminum on Parathyroid Hormone and Calcium Metabolism.

Aims: Aluminum is widely used in industry and it has been associated with several health hazards among exposed workers. To study the effect of aluminum on the parathyroid gland and the disturbance in calcium and phosphorus metabolism among workers exposed to aluminum in aluminum industry. Methodology: This study was conducted on fifty workers in an aluminum foundry, who were occupationally exposed to aluminum and were compared with fifty non-exposed individuals. Full history was taken, clinical examination and some laboratory investigations were done in the form of: CBC, kidney functions, serum PTH, serum calcium, serum phosphorus and serum aluminum. Plain X-ray was done for workers who were markedly complaining of musculoskeletal symptoms. Environmental measurement of aluminum dusts were carried out in selected workplaces. Study Design: Case control study of aluminum exposed workers. Place and Duration of Study: Aluminum industry in Ain-Helwan, Cairo, Egypt, 2012. Results: Statistically significant differences were found between exposed and control as regards prevalence of parathyroid and musculoskeletal disorders, serum level of the parathyroid hormone (PTH), serum calcium, serum phosphorus, serum aluminum, creatinine, RBCs count and also there was a statistically significant difference between exposed workers with osteopenia and exposed workers without osteopenia as regards serum aluminum level. The environmental measurements in the workplace were within the permissible limits in Egypt. Conclusion: The elevation of serum aluminum level in workers exposed to environmental level within the permissible limits was associated with disturbance in PTH, calcium and phosphorus metabolism, so these limits should be revised. Periodic medical examination of workers exposed to aluminum is a must; this should include clinical examination, analysis of aluminum in serum, measurement of serum electrolyte (calcium and phosphorus) and bone imaging.

Cross Talk between Oxidative Stress, PPAR- γ and RAS System in Diabetic Rat Heart Exposed to Ischemia / Reperfusion Injury.

The present study aimed at clarifying the cross talk between peroxisome proliferator-activated receptor-gamma (PPAR- γ), cardiac reactive Oxygen species (ROS) and Renin-Angiotensin System (RAS). Methods: A total of 90 male albino rats were used. The rats were divided into: Group 1: Control group, Group 2: Type 2 diabetic rats, Group 3: PPARγ agonist protected type 2 diabetic rats. Group 4: Antioxidant protected type2 diabetic rats, Group 5: Metformin treated type 2 diabetic rats. Blood samples were collected for measurement of FBS and fasting insulin. Half the number of each group was sacrificed and the heart excised and perfused, from the rest of the group small piece from the heart was taken for estimation of malondialdehyde (MDA), Angiotensin 2 Receptor (AT2R) and Angiotensin Converting Enzyme 2 (ACE2) gene expression. Results: Treatment with pioglitazone and Vitamin E significantly lowered blood glucose, insulin levels and Homeostasis Model Assessment Insulin Resistance (HOMA IR). However, values did not return to control values. Pioglitazone and Vitamin E improved myocardial performance and percentage recovery following ischemia reperfusion. The cardioprotective effect was more pronounced in the pioglitazone group. This positively correlated with decreased MDA levels and increased AT2R and ACE2 expression in cardiac tissue. Conclusion: Pioglitazone and Vitamin E in type 2 DM significantly offered cardioprotection through improving the diabetic condition and / or decreasing MDA levels.

Influence of adipose tissue derived mesenchymal stem cells in combination with injectable bone substitute on osteoclastogenesis in osteoporotic rats.

The present study was designed to evaluate the influence of adipose tissue derived mesenchymal stem cell (ASCs) with or without calcium phosphate composite on osteoclastogenesis in osteoporotic rats. Mesenchymal stem cells (MSCs) were harvested from adipose tissue of both the omentum and the inguinal fat pad of male rats, as the sex mismatch, to track the MSCs fate and to ensure their homing to the injured females' femurs. The isolated ASCs were characterized via the morphological appearance, multilineage potential and the PCR detection of CD29, CD44, CD106, CD14, CD34 and CD45 surface markers. Fifty adult female albino rats were enrolled in the current study. The rats were classified into five groups: group 1 was the gonad intact control, group 2 served as untreated ovariectomized (OVX) rats, group 3 was OVX rats treated with ASCs, group 4 was OVX rats treated with ASCs with injectable bone substitute (IBS) and group 5 was OVX rats treated with IBS. The serum levels of osteoprotegerin (OPG) and receptor activator of NF-қβ ligand (RANKL) were assayed using ELISA procedure. In addition, nuclear factor-κβ (NF-κβ) gene expression level was estimated in femur bones using real time –PCR. The isolated ASCs proved their MSCs identity via their morphological appearance and multilineage potential. In addition, the isolated ASCs showed positive expression for CD29, CD45, CD44 as well as CD106 and negative expression for CD34 and CD14. Besides, the positive expression of the Y-chromosome (sry) gene detected in the ASCs treated groups indicated that the systemically delivered single dose of undifferentiated ASCs was able to home at the females' femur bones. Adipose tissue derived mesenchymal stem cells (ASCs) injection with or without calcium phosphate composite in OVX rats reversed the effect of ovariectomy on the studied biomarkers causing significant increase in serum OPG level accompanied with significant decrease in serum RANKL level. Also, significant down regulation of NF-κβ gene expression in femur bones was detected in the treated groups compared with untreated OVX group. These results clarified the good influence of ASCs against osteoclastogenesis. In addition the combination of ASCs injection with osteoinductive material injectable calcium phosphate composite (IBS), may be useful to achieve the significant antiosteoporotic effects.

Effect of mesenchymal stem cells on anti-Thy1,1 induced kidney injury in albino rats

Objective: To evaluate the effect of mesenchymal stem cells (MSCs) in rats with anti-Thy1,1 nephritis. Methods: Female albino rats were divided into three groups, control group, anti-Thy1,1 group and treatment with i.v. MSCs group. MSCs were derived from bone marrow of male albino rats, Y-chromosome gene was detected by polymerase chain reaction in the kidney. Serum urea and creatinine were estimated for all groups. Kidney of all studied groups was examined histologically and histochemically (total carbohydrates and total proteins). DNA fragmentation and expression of α-SMA were detected. Results:Kidney of animals injected with anti-Thy1,1 showed inflammatory leucocytic infiltration, hypertrophied glomeruli, tubular necrosis and congestion in the renal blood vessels. The kidney tissue also showed reduction of carbohydrates and total proteins together with increase in apoptosis and in expression ofα-SMA. Moreover, the levels of urea and creatinine were elevated. Treating animals with MSCs revealed that kidney tissue displayed an improvement in the histological and histochemical changes. Apoptosis and α-SMA expression were decreased, and the levels of urea and creatinine decreased. Conclusions:The obtained results demonstrated the potential of MSCs to ameliorate the structure and function of the kidney in rats with anti-Thy1,1 nephritis possibly through the release of paracrine growth factor(s).

Skin tags, leptin, metabolic syndrome and change of the life style.

Background: Skin tags (STs), are papillomas commonly found in the neck and in the axillae of middle-aged and elderly people. Metabolic syndrome (MS) is a complex of interrelated risk factors for cardiovascular disease and diabetes. Epidemiologic studies of different ethnic populations have indicated that hyperleptinaemia and leptin resistance are strongly associated with MS. Aim: To study the possible relation of skin tags and leptin levels to MS guided by the International Diabetes Federation (IDF) diagnostic criteria. Methods: This study included 80 participants, 40 ST patients and 40 apparently healthy controls. Age, sex, waist circumference (WC), body mass index (BMI), smoking status, fasting glucose level, insulin level and insulin resistance were estimated as well as cholesterol, triglycerides, HDL, criteria of MS, and leptin levels. Results: The univariate analysis showed that WC, BMI, fasting glucose, insulin levels, insulin resistance, cholesterol, triglycerides, HDL, and leptin levels were significantly higher in ST patients compared to controls (P < 0.001). The multivariate analysis between MS components and ST showed that only high triglyceride levels (OR 1.205/95% CI 1.044-1.391/P = 0.011) and low HDL levels (OR 0.554/95% CI 0.384-0.800/P = 0.002) were significantly associated with ST. Multivariate linear regression analysis of the predictors of high plasma leptin levels, showed that high triglyceride levels (OR 0.287/95% CI 0.410-3.56/P = 0.014), and low HDL levels (OR -0.404/95% CI -8.7 to -2.08/P = 0.002) were significant predictors. Conclusion: The results of this study suggested that the presence of both ST and hyperleptinaemia in patients with STs may be associated with high levels of triglycerides and low levels of HDL and this could suggest that changing the life style of patients with ST may have a beneficial role.

Increased tissue leptin hormone level and mast cell count in skin tags: A possible role of adipoimmune in the growth of benign skin growths.

Background: Skin tags (ST) are common tumors. They mainly consist of loose fibrous tissue and occur on the neck and major flexures as small, soft, pedunculated protrusions. Decrease in endocrine, hormone level and other factors are thought to play a role in the evolution of ST. Leptin is an adipocyte-derived hormone that acts as a major regulatory hormone for food intake and energy homeostasis. Leptin deficiency or resistance can result in profound obesity and diabetes in humans. A role of mast cell in the pathogenesis of ST is well recognized. Aims: To investigate the role of leptin in the pathogenesis of ST and to clarify whether there is a correlation between mast cell count and leptin level in ST. Methods: Forty-five skin biopsies were taken from 15 patients with ST. From each patient, a biopsy of a large ST (length >4 mm), a small ST (length <2 mm) and a normal skin biopsy (as a control) were taken. The samples were processed for leptin level. Skin biopsies were stained with hematoxylin and eosin and toluidine blue-uranyl nitrate metachromatic method for mast cell count was used. Results: There was a significant increased level of leptin in the ST compared to the normal skin. It was highly significant in small ST than in big ST (P = 0.0001) and it was highly significant in small and big ST compared to controls, P = 0.0001 and P = 0.001, respectively. There was a significant increase in mast cell count in the ST, which did not correlate with the increased levels of leptin. Conclusion: This is the first report to demonstrate that tissue leptin may play a role in the pathogenesis of ST. The significant increase in the levels of leptin and mast cell count in ST may indicate a possible role of adipoimmune in the benign skin growths.