Molecular and Cellular Mechanisms Involved in Adipose-derived stem cell and their extracellular vesicles in an Experimental Model of Cardio- renal Syndrome type 3: Histological and Biochemical Study.

A cardio-renal syndrome (CRS) is a medical condition in which kidney problems are accompanied by heart problems and diagnosed when acute kidney injury contributes to the development of acute cardiac injury. Regenerative medicine is becoming increasingly interested in adipose stem cells. We evaluated the effect of both adipose-derived stem cell extracellular vesicles (ADSCs-EVs) and adipose stem cells (ADSCs) on an experimental model of CRSIII. In this study, isolation, and further identification of ADSCs and ADSCs-EVs by transmission electron microscopy and flow cytometric analysis. Cardio-renal syndrome in rats was induced by renal artery ligation RAL followed by a single dose injection of both ADSCs and ADSCs-EVs in separate groups. The effects of ADSCs-EVs and ADSCs against induced CRSIII were evaluated by both renal and cardiac oxidant/antioxidant biomarkers, renal function, and mRNA gene expression quantitation for atrial natriuretic peptide (ANP), p300, and myocyte enhancer factor 2 (MEF2C and MEF2A), as well as myocardin (MYOCD), as molecules associated with cardiac hypertrophy. Additionally, histological and immunohistochemical studies of cardiac and renal tissues were done. ADSCs-EVs were effectively isolated and characterized. ADSCs-EVs and ADSCs reversed induced CRSIII, evidenced by considerably decreased serum urea and creatinine levels. Returned oxidant/antioxidant stability, and decreased caspase 3-mediated apoptotic programmed cell death in cardiac and renal tissues. Additionally, they led to successful down-regulation of hypertrophic cardiac genes levels and reversed histopathological cardiac and renal injures. ADSCs-derived extracellular vesicles and ADSCs injection restored damaged cardiac and renal tissue and improved its function greatly following induced CRSIII. They could therefore be useful as a means of protecting the heart from the deleterious effects of acute renal injury and reprogramed injured cardiac cells by activating regenerative processes. SIMPLE SUMMARY: Cardiorenal syndrome (CRS) type III is a subcategory of CRS whereby acute kidney injury (AKI) could contribute to the development of acute cardiac dysfunction. This study provided innovatory data regarding the role of adipose-derived stem cell extracellular vesicles ADSCs-EVs and adipose stem cells (ADSCs) in acute renal and cardiac dysfunction and renal biopsy specimens in the form of interstitial inflammation/tubular degeneration. The main cause of renal and cardiac dysfunction is identified to be the activation and accumulation of inflammatory cells and oxidants in the interstitium, surrounded by increased amounts of extracellular matrix, and ADSCs-EVs have been proposed as a contributor factor. The study has evidenced that both ADSCs-EVs and adipose stem cells display beneficial effects on renal and cardiac tissues survival in terms of the frequent occurrence of cardio-renal syndrome, ADSC-EVs treatment repaired damaged renal and cardiac tissues and recovered their function. ADSC-EVs reversed the effects of cardio-renal syndrome and reprogramed injured cells by activating regenerative processes. The clinical significance of the results presented in future studies needs to be investigated further.

Anatomical study of the latissimus dorsi muscle flap / Estudio anatómico del colgajo del músculo latísimo del dorso

SUMMARY: The latissimus dorsi is a broad muscle that originates from the inferior thoracic spinous processes, thoracolumbar fascia, iliac crest, and inferior ribs. It inserts on the inferior aspect of the intertubercular groove of the humerus through a thin tendon. The study was conducted on 10 cadavers (7 male and 3 female). These specimens were dissected and examined to study the gross anatomical characteristics of the latissimus dorsi muscle. The dimensions of the latissimus dorsi muscle and its surface area were measured in all the cadavers. The branching pattern of the thoracodorsal vessels was recorded. The pedicle length and caliper were measured using Vernier calipers. On the 20 dissected sides, the thoracodorsal artery was found to be one of the terminal branches of the subscapular artery that originates in the axillary region. In 19 (95 %) cases, the thoracodorsal artery terminated in a bifurcation, giving off a medial and a lateral branch. The average size of the elevated flap of the latissimus dorsi muscle was 18 cm x 36 cm. The average pedicle length was 9.5 cm (range: 5 cm-14 cm), and the average diameter at its origin was 2.5 mm (range: 1.5 mm-3.5 mm). The average diameter of the vena comitans was 3.3 mm. The current study focuses on the anatomical features of the latissimus dorsi muscle and its blood supply to increase the success rate of operations in clinical practice.

RESUMEN: El músculo latísimo del dorso se origina en los procesos espinosos de las vértebras torácicas inferiores, la fascia toracolumbar, la cresta ilíaca y las costillas inferiores y se inserta en el surco intertubercular del húmero a través de un delgado tendón. El estudio se realizó en 10 cadáveres (7 mujeres y 3 hombres). Estos especímenes fueron disecados y examinados para estudiar las características anatómicas macroscópicas del músculo latísimo del dorso. En todos los cadáveres se midieron las dimensiones del músculo y su superficie. Se registró el patrón de ramificación de los vasos toracodorsales. La longitud del pedículo y el calibre se midieron con paquímetro Vernier. En los veinte lados disecados, se encontró que la arteria toracodorsal era una de las ramas terminales de la arteria subescapular que se originaba en la región axilar. En 19 (95 %) casos, la arteria toracodorsal terminaba bifurcándose en dos ramas, una rama medial y otra lateral. El tamaño promedio del colgajo elevado del músculo latísimo del dorso era de 18 cm x 36 cm. La longitud promedio del pedículo era de 9,5 cm (rango: 5 cm-14 cm), y el diámetro promedio en su origen era de 2,5 mm (rango: 1,5 mm-3,5 mm). El diámetro medio de la vena comitans era de 3,3 mm. El estudio actual se centra en las características anatómicas del músculo latísimo del dorso y su irrigación para aumentar la tasa de éxito de las operaciones en la práctica clínica.

Adipose-derived stem cell and their extracellular vesicles ameliorates immune function, and cardiac markers in experimental model of cardiorenal syndrome type III: TNF-α, IFN-γ and IL-10 cytokine production and their correlation with genotype.

Cardio-renal syndrome (CRS) denotes the convergence of heart-kidney interactions across several mechanisms. The current study is conducted to evaluate the anti-inflammatory role of adipose tissue-derived stem cells (ASCs) versus adipose stem cell-derived extracellular vesicles (ADSCs-EVs) in experimental model of cardiorenal syndrome type III. The study was conducted on 50 male rats that were equally divided to: group I (control group); Group II (experimental cardiorenal syndrome group) which induced by right renal artery ligation (ICRSIII); Group III (Sham-operated control group) which underwent surgical incision without renal artery ligation; Group IV (ICRSIII which received ADSCs-extracellular vesicles (ADSCs-EVs); Group V (ICRSIII which received adipose tissue stem cells (ASCs). Assessment of pro-inflammatory cytokines; IL-10, IL-1α, IL-6, IL-1 ß, IFN-γ, NF-α and their mRNA gene expression quantitation, (NGAL), and brain natriuretic peptide (BNP) as markers of cardiac dysfunction, as well as histopathological examination of renal tissue was examined by H& E, Masson trichrome and periodic acid-Schiff stains (PAS). The ICRS group exhibited significant acute tubular injury with tubular dilation, loss of brush borders, epithelial flattening, and occasional sloughed cells in lumen. Use of either ADSCs-EVs or ASCs significantly ameliorated the histological findings of tubular injury. Proinflammatory cytokines, BNP and NGAL were significantly elevated in ICRSIII group as compared to all other studied groups. Administration of ADSCs-EVs or ASCs led to significant decrease in all proinflammatory cytokines as well as BNP and NGAL levels with no significant difference between them. In conclusion, ADSCs-EXs and ASCs exhibited significant repairing effects in experimental-induced cardiorenal syndrome type III as evidenced by amelioration of histological findings of tubular injury, anti-inflammatory effects, and the significant decrease in markers of cardiac dysfunction. ADSC-EVs reprogramed injured cardiac cells by activating regenerative processes.

The biomechanistic aspects of renal cortical injury induced by diesel exhaust particles in rats and the renoprotective contribution of quercetin pretreatment: Histological and biochemical study.

Although several studies have reported a toxic effect of diesel exhaust particles (DEP) exposure on the kidney tissues, the involvement of autophagy/NF-kB signaling as encountered mechanisms and the protective effects of a natural flavonoid, quercetin on DEP remains unclear. Thirty-two albino rats were divided as control, quercetin-treated (60 mg/kg, oral), DEP-exposed (0.5 mg/kg, intra-tracheal), and quercetin/DEP-exposed groups. Specimens of the renal cortex were subjected to histo-biochemical study and immunohistochemical analysis using anti-NF-kB, and anti-LC3ß antibodies followed by morphometric and statistical analyses. The expression level of autophagy genes was quantitatively evaluated using RT-PCR, as well. The DEP-exposed rats showed an elevation in the renal tissue levels of MDA and a decrease in the catalase and superoxide dismutase (p < .05). Histologically, there were cytoplasmic vacuolar changes in the lining cells of the renal tubules, glomerular atrophy, and vascular congestion. In addition, renal inflammation was evident as confirmed by the increased NF-kB immunoexpression. Moreover, the gene expression of Becn1, ATG5, and LC3ß increased (p <. 0) due to DEP exposure. Conversely, quercetin pretreatment improved these renal histo-biochemical alterations (p < .05) and regulated autophagy/NF-kB pathways. Overall, the study proved the renal toxicity mediated by DEP exposure via precipitating renal inflammation, autophagy activation, and oxidative stress. Quercetin pretreatment could antagonize such machinery to protect the kidney against DEP.

Medical Students' Feedback of Applying the Virtual Dissection Table (Anatomage) in Learning Anatomy: A Cross-sectional Descriptive Study.

OBJECTIVE: Conventional cadaver dissection is the main learning tool for studying human anatomy. Other tools have been developed to add another dimension of depth to anatomy teaching, such as Anatomage. 3D Anatomage is a touch interactive anatomy virtual dissection table used in anatomy education. The aim of this study was to address students' opinions on applying the virtual dissection table (3D Anatomage) as an additional tool to cadaver dissection in learning anatomy. METHODS: An electronic questionnaire consisted of 6 questions that included items regarding the effect of using 3D Anatomage on students' deep understanding of anatomy topics, the locations and relationships of the different internal body structures and the application of anatomical knowledge. The survey was completed by 78 medical students. RESULTS: The results of this study showed that the majority of students preferred using 3D Anatomage as an additional tool to cadaver dissection for learning anatomy since it enhances active learning, and approximately 89% of students agreed that 3D Anatomage helped them to better understand the relationships between internal structures and visualizing the body system. Additionally, approximately 72% of the students indicated that the imaging facility in 3D Anatomage was useful for enabling their understanding of anatomy as it is envisioned through medical imaging. CONCLUSION: In conclusion, using the 3D Anatomage virtual dissection table is effective in anatomy education, and its use is recommended as an anatomy learning resource in addition to cadavers.

Autophagy Promotes the Survival of Adipose Mesenchymal Stem/Stromal Cells and Enhances Their Therapeutic Effects in Cisplatin-Induced Liver Injury via Modulating TGF-ß1/Smad and PI3K/AKT Signaling Pathways.

Autophagy is a key metabolic process where cells can recycle its proteins and organelles to regenerate its own cellular building blocks. Chemotherapy is indispensable for cancer treatment but associated with various side-effects, including organ damage. Stem cell-based therapy is a promising approach for reducing chemotherapeutic side effects, however, one of its main culprits is the poor survival of transplanted stem cells in damaged tissues. Here, we aimed to test the effects of activating autophagy in adipose-derived mesenchymal stem/stromal cells (ADSCs) on the survival of ADSCs, and their therapeutic value in cisplatin-induced liver injury model. Autophagy was activated in ADSCs by rapamycin (50 nM/L) for two hours before transplantation and were compared to non-preconditioned ADSCs. Rapamycin preconditioning resulted in activated autophagy and improved survival of ADSCs achieved by increased autophagosomes, upregulated autophagy-specific LC3-II gene, decreased protein degradation/ubiquitination by downregulated p62 gene, downregulated mTOR gene, and finally, upregulated antiapoptotic BCL-2 gene. In addition, autophagic ADSCs transplantation in the cisplatin liver injury model, liver biochemical parameters (AST, ALT and albumin), lipid peroxidation (MDA), antioxidant profile (SOD and GPX) and histopathological picture were improved, approaching near-normal conditions. These promising autophagic ADSCs effects were achieved by modulation of components in TGF-ß1/Smad and PI3K-AKT signaling pathways, besides reducing NF-κB gene expression (marker for inflammation), reducing TGF-ß1 levels (marker for fibrosis) and increasing SDF-1 levels (liver regeneration marker) in liver. Therefore, current results highlight the importance of autophagy in augmenting the therapeutic potential of stem cell therapy in alleviating cisplatin-associated liver damage and opens the path for improved cell-based therapies, in general, and with chemotherapeutics, in particular.

Anatomical study and clinical importance of the inferior epigastric artery / Estudio anatómico e importancia clínica de la arteria epigástrica inferior

SUMMARY: The inferior epigastric artery (IEA) is a major blood vessel that supplies the anterior abdominal wall. The aim of the current study was to provide clinicians, surgeons, and obstetricians with sufficient anatomical data on the inferior epigastric artery, such as its origin and branching pattern. The study included 20 embalmed cadavers, these cadavers were dissected, and the inferior epigastric artery and vena comitans/venae comitantes were identified and traced downwards to the external iliac vessels. The origins, caliber, course and pedicle length of both the artery and the vein(s) were studied. The inferior epigastric artery arose independently from the distal external iliac artery deep to the inguinal ligament in 19 (95 %) cadavers. The artery entered the rectus abdominis muscle at its middle third in 13 (65 %) cases and at its lower third in the remaining specimens. In this study, we found that the artery divided into two branches in 18 (90 %) of the cases; in the remaining two cases, it continued as one trunk. The average pedicle length was 7.2 cm. The mean caliber of the IEA was 3.7 mm. In 18 (90 %) dissections, the venous drainage consisted of a pair of venae comitantes that united to form a common vessel at their draining point on the external iliac vein. The average diameter was 3.9 mm. The current study focuses on the anatomical features of the inferior epigastric artery to increase the success rate of abdominal and pelvic operations in clinical practice.

RESUMEN: La arteria epigástrica inferior (AEI) es un vaso sanguíneo principal que irriga la pared abdominal anterior. El objetivo del presente estudio fue proporcionar a los médicos, cirujanos y obstetras suficientes datos anatómicos sobre la arteria epigástrica inferior, como su origen y patrón de ramificación. El estudio incluyó 20 cadáveres embalsamados, los que se disecaron y se identificó la arteria epigástrica inferior y la vena concomitante y se siguieron hasta los vasos ilíacos externos. Se estudiaron los orígenes, calibre, trayecto y longitud del pedículo tanto de la arteria como de la (s) vena (s). La arteria epigástrica inferior surgió independientemente de la arteria ilíaca externa profunda al ligamento inguinal en 19 (95 %) cadáveres. La arteria ingresó al músculo recto del abdomen en su tercio medio en 13 (65 %) casos y en su tercio inferior en las muestras restantes. En este estudio, encontramos que la arteria se dividió en dos ramas en 18 (90 %) de los casos; en los dos casos restantes, continuó como un tronco. La longitud media del pedículo fue de 7,2 cm. El calibre medio del AEI fue de 3,7 mm. En 18 (90 %) disecciones, el drenaje venoso consistió en un par de venas concomitantes las que formaron un vaso común en su punto de drenaje en la vena ilíaca externa. El diámetro medio fue de 3,9 mm. El estudio actual se centra en las características anatómicas de la arteria epigástrica inferior con el propósito de mejorar la tasa de éxito de las cirugías abdominales y pélvicas en la práctica clínica.

Structural and chemical role of mesenchymal stem cells and resveratrol in regulation of apoptotic -induced genes in Bisphenol-A induced uterine damage in adult female albino rats.

The probable beneficial effects of mesenchymal stem cells (MSCs) and resveratrol were assessed in an experimental model of Bisphenol-A (BPA)-evident uterine damage in rats. Thirty-five albino rats were involved and equally divided into five groups: Group I: negative control rats received usual diet, Group II: positive control rats received BPA by oral gavage for 15 days, Group III: BPA-treated rats received single oral gavage of resveratrol daily for two weeks, Group IV: BPA-treated rats received a single intravenous dose of MSCs and Group V: BPA-treated rats received combined treatment of resveratrol and MSCs. Oxidative stress markers, apoptosis-related genes, and gonadal hormones were assessed. Histological and immunohistochemical examination of uterine tissue was conducted for TGF-ß 1. Caspases-3, 8, and 9 (Casp3, Casp8, Casp9) genes were assessed in uterine tissues by quantitative real-time PCR. Results revealed that BPA induced significant changes in the endometrial tissue, inflammatory cell infiltration, focal blood extravasation, increase in collagen fibers, decrease in PAS staining, and increase in TGF-ß 1 immunoreactivity. BPA also induced a significant increase in oxidative stress markers; malondialdehyde (MDA), SOD, CAT, and apoptosis-related genes. BPA induced a significant change in blood levels of gonadal hormones; a significant increase in FSH and a significant decrease in estradiol (E2) and progesterone (P). Treatment with either resveratrol, MSCs, or a combination of them resulted in significant enhancement of histological findings, restoration of gonadal hormones to near-normal levels, and a significant decrease in oxidative stress markers and apoptosis genes. Combined treatment with resveratrol and MSCs demonstrated more significant therapeutic effects as regard to the studied parameters in association with rat groups treated with either MSCs or resveratrol separately.

Extracellular vesicles derived from bone marrow mesenchymal stem cells repair functional and structural rat adrenal gland damage induced by fluoride.

The adrenal glands have striking morpho-biochemical features that render them vulnerable to the effects of toxins. AIMS: This study was conducted to explore the therapeutic utility of extracellular vesicles derived from bone marrow mesenchymal stem cells (BMSC-EVs) against fluoride-induced adrenal toxicity. MATERIALS AND METHODS: The work included isolation and further identification of BMSC-EVs by transmission electron microscopy and flow cytometric analysis. Adrenal toxicity in rats was induced by oral administration of 300 ppm of sodium fluoride (NaF) in drinking water for 60 days followed by a single dose injection of BMSC-EVs. The effects of BMSC-EVs against NaF was evaluated by adrenal oxidant/antioxidant biomarkers, hormonal assay of plasma adrenocorticotrophic hormone (ACTH) and corticosterone (CORT) and mRNA gene expression quantitation for adrenal cortical steroidogenic pathway-encoding genes. Histopathological examination of the adrenal tissue was performed. KEY FINDINGS: BMSC-EVs were effectively isolated and characterized. NaF exposure decreased adrenal superoxide dismutase and catalase activities, increased adrenal malondialdehyde levels, elevated plasma ACTH, diminished CORT concentrations and downregulated the adrenal cortical steroidogenic pathway-encoding genes. In addition, NaF-induced marked adrenal histopathological lesions. SIGNIFICANCE: BMSC-EVs treatment repaired damaged adrenal tissue and recovered its function greatly following NaF consumption. BMSC-EVs reversed the toxic effects of NaF and reprogramed injured adrenal cells by activating regenerative processes.

Does oregano protect against testicular toxicity produced by ethylene glycol in adult male albino rat? / ¿El orégano protege contra la toxicidad testicular producida por etilenglicol en ratas macho albinas adultas?

SUMMARY: Origanum vulgare Linn has traditionally been used as a diuretic and antispasmodic. Therefore, we investigated the active extract of Origanum vulgare for possible andrological effect and preventive effects against testicular damage using ethylene glycol rat model of testicular damage, to rationalize its medicinal use. Male Wistar rats received lithogenic treatment comprising of 0.75 % ethylene glycol injection twice with one day interval, then in drinking water, active extract of Origanum vulgare treatment (20 mg/kg) was given for 3 weeks to prevent toxic damage including loss of body weight gain and appetite, Following oral administration of EGME, a rapid decrease in testis weight associated with testicular cell damage was observed. Origanum vulgare treatment (20 mg/kg) prevented as well as reversed toxic changes including loss of body weight gain.

RESUMEN: Origanum vulgare Linn se ha usado tradicionalmente como diurético y antiespasmódico. Por lo tanto, investigamos el extracto activo de Origanum vulgare por su posible efecto andrológico y efectos preventivos contra el daño testicular utilizando el modelo de rata de etilenglicol de daño testicular. El objetivo del estudio fue racionalizar su uso medicinal. Su utilizaron ratas Wistar macho que recibieron un tratamiento litogénico de una inyección de etilenglicol al 0,75 %, dos veces con un intervalo de un día, y luego se administró en agua potable. Se administró el extracto activo del tratamiento con Origanum vulgare (20 mg / kg) durante 3 semanas con el objetivo de prevenir el daño tóxico, la pérdida de peso corporal y el apetito. Tras la administración oral de EGME, se observó una rápida disminución del peso de los testículos asociada al daño de las células testiculares. El tratamiento con Origanum vulgare (20 mg / kg) logró prevenir y revertir las alteraciones tóxicas, incluyendo la pérdida de peso corporal.