Dina Sabry

BACKGROUND: Diabetic foot ulceration is a serious chronic complication of diabetes mellitus characterized by high disability, mortality, and morbidity. Platelet-rich plasma (PRP) has been widely used for diabetic wound healing due to its high content of growth factors. However, its application is limited due to the rapid degradation of growth factors. The present study aimed to evaluate the efficacy of combined adipose-derived mesenchymal stem cells (ADSCs) and PRP therapy in promoting diabetic wound healing in relation to the Notch signaling pathway.

METHODS: Albino rats were allocated into 6 groups [control (unwounded), sham (wounded but non-diabetic), diabetic, PRP-treated, ADSC-treated, and PRP+ADSCs-treated groups]. The effect of individual and combined therapy was evaluated by assessing wound closure rate, epidermal thickness, dermal collagen, and angiogenesis. Moreover, gene and protein expression of key elements of the Notch signaling pathway (Notch1, Delta-like canonical Notch ligand 4 (DLL4), Hairy Enhancer of Split-1 (Hes1), Hey1, Jagged-1), gene expression of angiogenic marker (vascular endothelial growth factor and stromal cell-derived factor 1) and epidermal stem cells (EPSCs) related gene (ß1 Integrin) were assessed.

RESULTS: Our data showed better wound healing of PRP+ADSCs compared to their individual use after 7 and 14 days as the combined therapy caused reepithelialization and granulation tissue formation with a marked increase in area percentage of collagen, epidermal thickness, and angiogenesis. Moreover, Notch signaling was significantly downregulated, and EPSC proliferation and recruitment were enhanced compared to other treated groups and diabetic groups.

CONCLUSIONS: These data demonstrated that PRP and ADSCs combined therapy significantly accelerated healing of diabetic wounds induced experimentally in rats via modulating the Notch pathway, promoting angiogenesis and EPSC proliferation.

Background: Perchlorate is a strong oxidizing agent and has many adverse health effects. This study investigated the potential oxidative, apoptotic, and endocrinal toxic effects of perchlorate in human placenta-derived mesenchymal stem cells (HP-MSCs).

Methods: HP-MSCs were treated with two doses of perchlorate (5 and 15 μg/L) for three days. The perchlorate's effects were detected by histopathological examination, aromatase/CYP19 A1 activity, reactive oxygen species production (ROS), and Caspase-3 expression.

Results: The highest perchlorate concentration (15 μg/L) caused significant placental histopathological changes. The placental cell viability was significantly affected by a significant increase in ROS generation; caspase-3 expression, and a significant reduction of CYP 19 activity. Despite the slight induction effect of the lowest perchlorate concentration (5 μg/L) on caspase 3 expression, CYP 19 activity, and ROS generation, it did not affect placental cellular viability.

Conclusion: This study suggested that perchlorate could modulate aromatase activity and placental cytotoxicity. The continuous monitoring of the actual perchlorate exposure is needed and could be cost-effective.

OBJECTIVES: To determine the effect of intra-articular injection of platelet-rich plasma (PRP) in patients with primary knee osteoarthritis (OA) by clinical evaluation and ultrasonographic (US) assessment of cartilage thickness.

PATIENTS AND METHODS: A total of 100 patients with mild to severe primary knee OA using the Kellgren-Lawrence (K-L) grading scale were included and divided into two groups. Group I included 50 patients who were given two intra-articular knee injections of PRP, 1 week apart; Group II included 50 patients who received non-steroidal anti-inflammatory drugs (NSAIDs) and chondroprotective drugs. Functional assessment of all OA patients done using the basal WOMAC score, at 2 and 6 months.US assessment of femoral condylar cartilage thickness was conducted basally and at 6 months.

RESULTS: Improvement of WOMAC score was observed at 2 and 6 months in Group I following PRP injection compared to Group II (p values < 0.001), The improvement of WOMAC in Group I occurred in all severity degrees of OA (p < 0.001). Moreover, a significant increase in cartilage thickness at the intercondylar area (ICA) at 6 months relative to baseline assessment by US in Group I (p = 0.041) was found.

CONCLUSION: Treatment with PRP injections can reduce pain and improve knee function in patients with various degrees of articular degeneration. Further studies are needed to clarify the anabolic effect of PRP on the articular cartilage.

Background: Diabetes mellitus (DM) is a metabolic disorder resulting from hyperglycemia. Hyperglycemia contributes to oxidative stress, and the release of advanced glycation end products (AGEs) further promotes disease pathogenesis. Uncontrolled diabetes reflects great oral complications and affects human oral health. So, the present study aimed to assess the effects of photobiomodulation therapy (PBMT) and Metformin on proliferation and viability of human periodontal ligament stem cells (HPDLSCs) cultured in high glucose medium.

Methods: HPDLSCs were collected, isolated, and characterized and then divided into eight groups. Addition of extra glucose to diabetic groups 24 hours before cell irradiations. Metformin was added to half of the diabetic groups. Cells were irradiated with 808 nm diode laser 24, 48 hours. Cell viability was analyzed with MTT assay 24 hours post-irradiation to detect cell viability in each group. Real-time (PCR) was used to evaluate gene expression of and and the effect of PBMT on Pathway. ELISA reader was used to evaluating cell viability through (ROS, TNF-α, IL-10) protein levels after cell irradiation.

Results: Photobiomodulation at 1, 2, and 3 J/cm2 combined with metformin significantly promoted diabetic cell lines of HPDLSCs viability (in MTT assay and ELISA reader of ROS, TNF-α, IL-10 results) and gene expression of , and levels (p< 0.05).

Conclusion: photobiomodulation with 3 J/cm combined with metformin enhanced proliferation and viability of diabetic cell lines of HPDLSCs and thus could improve differentiation and function of diabetic cell lines of HPDLSCs with minimum side effects.

Cisplatin (CP) is extensively used in the medical oncology field for malignancy treatment, but its use is associated with neurological side effects that compromise the patients' quality of life. Cytotherapy is a new treatment strategy for tissue damage that has recently emerged. The use of bone marrow-derived mesenchymal stem cells (BM-MSCs) was investigated for its therapeutic potential against CP-induced chemobrain as well as various models of brain damage. This study was carried out to elucidate, for the first time, the role of the intravenous injection (IV) of BM-MSCs against CP-induced neurotoxicity in a rat model through investigation of the parameters of oxidative stress, inflammation, and apoptosis in brain tissue. A rat model of neurotoxicity was generated by intraperitoneal injection of 7.5 mg/kg CP while 2 × 10 BM-MSCs was given by IV as a therapeutic dose. Injection of CP led to a significant rise in malondialdehyde and nitric oxide levels accompanied by a marked depletion of superoxide dismutase and reduced glutathione content in brain tissue in comparison to the normal control (NC) rats. Furthermore, a remarkable rise in the brain levels of inflammatory cytokines interleukin (IL)-1β and IL-6, together with the expression of apoptotic marker caspase-3, and the downregulation of the brain expression of proliferating marker Ki-67 in brain tissue were detected in the CP group compared to the NC group. Histopathological alterations were observed in the brain tissue of the CP group. BM-MSCs mitigated the biochemical and histopathological alterations induced by CP without affecting brain cell proliferation. BM-MSCs could be used as a promising neuroprotective agent against CP-induced neurotoxicity.

Despite that cyclosporine-A (CsA) is a widely used immunosuppressive drug, its nephrotoxic effect limits its long-term administration. Herein we tried to investigate its renal effect on endothelial dysfunction targeting the hypoxia-inducible factor (HIF-1α) / vascular endothelial growth factor (VEGF) / endothelial nitric oxide synthase (eNOS) pathway and the possible modulation by nicorandil. Eight groups of adult male Wistar rats were included: (1) control; (2) vehicle group (received oil); (3) glibenclamide 5 mg·kg·day administered orally; (4) nicorandil 10 mg·kg·day administered orally; (5) CsA 25 mg·kg·day administered orally; (6) combined administration of CsA and nicorandil; (7) glibenclamide was added to CsA; and (8) both CsA and nicorandil were combined with glibenclamide. The treatment continued for six weeks. Combined nicorandil with CsA improved renal function deterioration initiated by CsA. CsA decreased the renal expression levels ( < 0.001) of HIF-1α, eNOS, and VEGF, inducing endothelial dysfunction and triggering inflammation, and upregulated the profibrotic marker transforming growth factor (TGF-β). Nicorandil fixed the disturbed HIF-1α/VEGF/eNOS signaling. Nicorandil corrected the renal functions, confirmed by the improved histological glomerular tuft retraction that was obvious in the CsA group, without significant influence by glibenclamide. Proper protection from CsA-induced nephrotoxicity was achieved by nicorandil. Nicorandil reversed the disturbed HIF-1α/VEGF/eNOS pathway created by CsA.

Occupational stress is a major health problem among nurses. Critical care nurses appear to experience more stress at work compared to others. Stress is associated with multiple system disorders, hormonal, and immunological disturbances, and genetic effects. The aim of our study was the detection of health effects of work-related stress and to investigate the link between stress and immune response, alterations of hormones, and expression of micro-RNA (miRNA) among critical care nurses. An exposed 80 critical care nurses matched to 80 controls were involved in our study. Full history, psychological assessment using the General Health Questionnaire (GHQ12) and a complete clinical examination were done for both groups. Serum interleukin (IL)-6, IL-10, luteinizing hormone (LH), follicle-stimulating hormone, thyroid-stimulating hormone (TSH), free triiodothyronine, and free thyroxine (FT4) were measured by enzyme-linked immunosorbent assay, micro-RNA26, and 142 extractions. The exposed group had a mean age of 41 ± 10 years old and mean work duration of 22 ± 9.7 years, matched to 80 controls. The exposed group (32.5%) was associated with severe psychological distress (GHQ scores > 20) compared to only 5% among controls. In addition, the exposed group had a significantly higher level of miRNA 26, miRNA 142, TSH, LH, and IL-6 when compared to the control group. However, there a significantly lower level of FT4 among the exposed group compared to the control group, there were no statistically significant differences between the studied participants regarging FT3,FSH and IL-10 levels. Stress is prevalent among critical care nurses and is reflected on their psychological health with an increase in inflammatory cytokines and disturbances in endocrine functions.

We speculated impacts of BM-MSCs and UC-EPCs on reversal of hepatic injury induced by carbon tetrachloride (CCl4). Fifty adult rats were divided into five groups: control group, CCl4A group, CCl4B group, CCl4/BM-MSCs group and CCl4/UC-EPCs group. Blood samples were driven to measure concentration of albumin and ALT. Quantitative expression of HGF, TGF-β, MMP-2, and VEGF were assessed by PCR. Histological and immunohistochemistry examination of the liver tissue were performed. There was elevating albumin ( < .05) and reducing ALT ( < .05) concentrations in groups treated with BM-MSCs and UC-EPCs compared to untreated CCL4A&B groups. UC-EPCs treated group have significantly higher MMP-2 and VEGF ( < .01) genes expression than BM-MSCs treated group. Furthermore, UC-EPCs were more valuable than BMMSCs in increasing gene expression of HGF ( < .05) and immunohistochemistry of α-SMA and Ki-67 ( < .01). BM-MSCs have significantly lower TGF-β ( < .00) compared to UC-EPCs. This study highlighted on liver regeneration role of both UC-EPCs and BM-MSCs in liver fibrosis.

AIM: The aim of the current study was to evaluate the therapeutic and regenerative effects of MSCs derived exosomes in the treatment of type 1 DM and to compare its effects with MSCs themselves. The experiment was done on forty albino rats grouped as follows, group (1): Ten healthy rats, group (2): Ten induced type 1 DM rats, group (3): Ten induced type 1 DM rats received exosomes intraperitoneally, and group (4): Ten induced type 1 DM rats received MSCs intraperitoneally. Serum glucose and plasma insulin levels were assessed weekly. QRT-PCR was done to assess regeneration of pancreatic beta cells by measuring insulin, Pdx1, Smad2, Smad3 and TGFβ genes. Additionally, histopathological and immune-histochemical examinations were done to confirm pancreatic tissue regeneration.

RESULTS: Regarding the assessed genes (insulin, Pdx1, Smad2, Smad3 and Tgfβ) gene expression in MSCs treated group showed significant increase compared to diabetic group (p value < 0.001) and gene expression in exosomes treated group was increased significantly compared to diabetic and MSCs treated groups (p value < 0.001). Histopathological and immune-histochemical examination revealed regeneration of pancreatic islets in both treated groups.

CONCLUSION: MSCs Derived exosomes showed superior therapeutic and regenerative results than MSCs themselves.

Background: To prevail over diabetes mellitus and its numerous complications, researchers are seeking new therapies. Exosomes are natural cargo of functional proteins and can be used as a therapeutic delivery of these molecules.

Objective: The aim of this study was to evaluate the effect of exosomes derived from bone marrow mesenchymal stem cells (BM-MSCs) as a therapeutic intervention in salivary gland diabetic complications.

Methods: Ten adult healthy male Albino rats, weighing about 150-200 g were grouped into 2 groups. Diabetic group I: consisted of 5 streptozotocin (STZ)-induced diabetic rats. Exosomes treated group II: consisted of 5 STZ-induced diabetic rats, each animal received a single injection of exosomes (100 μg/kg/dose suspended in 0.2 ml PBS) through the tail vein. All animals were sacrificed after 5 weeks from the beginning of the experiment. Submandibular salivary gland samples were excised and processed for histological, ultrastructural examination and PCR for TGFβ, Smad2 and Smad3. Blood glucose level was monitored weekly, salivary IgA and serum amylase were evaluated before and after diabetes induction and at the end of the experiment.

Results: Histological and ultrastructural results of the exosomes treated group were promising regarding the glandular and ductal elements with less fibrosis observed. Results of PCR supported the role of exosomes to inhibit the diabetic sequalae in salivary gland and its complications through inhibiting TGFβ and its related pathway via Smad2 and Smad3. Blood glucose levels were reduced. In addition, salivary glands' function was improved as evidenced by reduction in serum amylase and salivary IgA.

Conclusion: BM-MSC-derived exosomes could be a novel therapeutic strategy for diabetic complications involving salivary glands.

INTRODUCTION: Human exposure to heavy metals is a potential risk for developing cognitive impairment. Aluminum (Al) foundry is one of industries that involve occupational exposure to different metals.

AIM OF THE WORK: to evaluate the cognitive performance of Aluminum foundry workers in relation to different metals exposure.

MATERIALS AND METHODS: a cross sectional study conducted on 75 Al foundry workers and 75 non-occupationally exposed subjects as controls. Personal interview with specially designed questionnaire, Assessment of cognitive functions done using Montreal cognitive assessment (MocA), Stress, depression and sleep were also assessed. Serum levels of Aluminum (AL), Lead (Pb), manganese (Mn), Zinc (Zn) and tau protein were measured.

RESULTS: Exposed group showed significant increase in serum levels of Aluminum, lead, Manganese and tau protein, p value < 0.005 (mean ± SD 0.56 ± 0.18, 22.3 ± 5.01, 42.04 ± 7.4, 1.53 ± 0.58 Vs 0.36 ± 0.11, 13.4 ± 1.29, 39.4 ± 4.4, 1.03 ± 0.44 respectively) with significant decrease of zinc level compared to control (mean ± SD 46.4 ± 5.2 Vs 88.8 ± 6.04, p value 0.005). There was a significant decrease MocA scores among exposed population, (mean ± SD 24.4 ± 3.4 compared to 28.4 ± 1.3 in non exposed, p value < 0.005). which was affected by serum levels of lead, aluminum, manganese and tau protein (β -0.165, -8.958, -.286, -2.341 respectively and p < 0.005).Stress scores was higher in exposed workers than control but not affecting cognitive performance.

CONCLUSION: occupational exposure to metals can cause cognitive dysfunction which may be subtle, so there is a need for formal cognitive testing at baseline, and on regular intervals during working period. Serum tau protein could be used as a prognostic biomarker for the hazardous effect of occupational exposure to these metals on the neuronal cells.

Interleukin 17 (IL-17) is one of the pro-inflammatory cytokine. Psoriasin is a noticeably over-expressed protein found in the skin lesions of psoriatic patients. Our current study was planned to examine the association of (- 947 A/G) single nucleotide polymorphism (SNP) in IL-17RA promoter region (rs4819554) with psoriasis susceptibility in Egyptian psoriatic patients. Our study included 100 patients and 100, age as well as sex matched, control groups. IL-17RA SNP association was studied using allelic discrimination. RT-qPCR and ELISA were done to assess IL-17 expression. ELISA was performed to assess psoriasin expression. Our study showed a significant association between IL-17 rs4819554 SNP and psoriasis risk, evidenced by higher G allele and AG genotype frequencies in psoriatic patients when compared to controls (allelic: OR 2.283, 95% CI 1.321-3.946, p = 0.003, and genotype: OR 3.026, 95% CI 1.356-6.752, p = 0.007). Additionally, serum psoriasin level was significantly increased when comparing psoriatic patients to controls (p = 0.0003). Moreover, significant increase in IL 17 gene and protein level in AA, AG psoriatic genotypes compared to the corresponding genotypes in normal control (p = 0.0004). IL-17 rs4819554 is significantly associated with psoriasis, and with psoriasin level, in the Egyptian population.

BACKGROUND AND STUDY AIMS: To investigate whether the measurement of liver stiffness (LSM) using fibroscan and the serum Cancer Stem Cells (CSC): Ep-CAM and cytokeratin-19, could predict the recurrence of hepatocellular carcinoma (HCC) and their impact on clinical outcome and overall survival.

PATIENTS AND METHODS: This is a prospective study, including 179 HCV-related HCC patients. All patients were treated following the BCLC guidelines. All HCC patients had transient elastography, measurements of Ep-CAM and cytokeratin-19 before and six months post-treatment. We looked for predictors of recurrence and performed a survival analysis using Kaplan-Meier estimates.

RESULTS: TACE was the most common procedure (77.1%), followed by microwave ablation (15.6%). Complete ablation was achieved in 97 patients; 55 of them developed HCC recurrence. After treatment, LSM increased significantly with a significant reduction in CSCs levels in complete and partial response groups. The median time to observe any recurrence was 14 months. LSM increased significantly post-treatment in patients with recurrence versus no recurrence. Higher levels of CSCs were recorded at baseline and post-treatment in patients with recurrence but without statistical significance. We used univariate analysis to predict the time of recurrence by determining baseline CK-19 and platelet levels as the key factors, while the multivariate analysis determined platelet count as a single factor. The univariate analysis for prediction of overall survival included several factors, LSM and EpCAM (baseline and post-ablation) among them, while multivariate analysis included factors such as Child score B and incomplete ablation.

CONCLUSION: Dynamic changes were observed in LSM and CSCs levels in response to HCC treatment and tumour recurrence. Child score and complete ablation are factors that significantly affect survival.

This study aimed to develop valsartan (VAL)-loaded mixed micelles and investigate their cardioprotective potential and molecular mechanisms through Mhrt/Nrf2 and Trx1 pathways. VAL-loaded mixed micelles have not been elaborated and their impact on Mhrt/Nrf2 and Trx1 pathways has not been yet inspected. VAL-loaded mixed micelles were prepared, incorporating Pluronic F127 and Tween 80, adopting thin-film hydration method. The micelles were evaluated for drug entrapment efficiency, loading characteristics, particle size, morphology, drug release and micelles storage stability. The pharmacokinetic studies were explored in rats. Also, VAL suspension and mixed micelles were tested in cisplatin-induced cardiotoxicity in rats either pre to or simultaneously with cisplatin. RNA expression of lnc Mhrt and protein expression of Nrf2, Trx1, Ask1, AMPK and caspase 3, oxidative stress and cardiac injury markers besides tailed DNA% by comet assay were assessed. Pharmacokinetic studies evoked a 3.75-fold increase in oral bioavailability as compared with VAL suspension. Overall, treatment with VAL-loaded mixed micelles was superior to VAL suspension in decreasing oxidative stress and cardiac injury markers and restoring the abnormalities occurred in Mhrt/Nrf2 and Trx1 pathways. Thus, mixed micelles would be promising nanocarrier for the engineering of VAL with reinforced pharmacokinetics and cardioprotection characteristics.

OBJECTIVE: To elucidate the effect of Alzheimer's disease on the structure of circumvallate papilla taste buds and the possible role of exosomes on the taste buds in Alzheimer's disease.

DESIGN: Forty two ovariectomized female adult albino rats were utilized and divided into: Group I: received vehicle. Group II: received aluminum chloride to induce Alzheimer's disease. Group III: after the induction of Alzheimer's disease, each rat received single dose of exosomes then left for 4 weeks. The circumvallate papillae were prepared for examination by light and transmission electron microscope.

STATISTICAL ANALYSIS: histomorphometric data were statistically analyzed.

RESULTS: Histological examination of circumvallate papilla in Group I showed normal histological features. Group II revealed distorted features. Group III illustrated nearly normal histological features of circumvallate. Silver impregnation results showed apparently great number of heavily impregnated glossopharyngeal nerve fibers in both Groups I & III but markedly decreased in Group II. Synaptophysin-immunoreactivity was strong in Group I, mild in Group II and moderate in Group III. The ultra-structural examination of taste bud cells revealed normal features in Group I, distorted features in Group II and almost normal features in Group III. Statistically highest mean of Synaptophysin-immunoreactivity area% was for Group I, followed by Group III, and the least value was for Group II.

CONCLUSIONS: Alzheimer's disease has degenerative effects. Bone marrow mesenchymal stem cell (BM-MSC)-derived exosomes have the ability to improve the destructive changes induced by Alzheimer's disease.

BACKGROUND: Glycolic acid (GA) and salicylic acid (SA) peels have been used separately for acne treatment, not as a sequential peel.

AIM: To evaluate the efficacy and safety of sequential peeling with 70% GA and 20% SA as a monotherapy and as an adjuvant to systemic doxycycline in treatment of mild to moderate acne and the effect on serum interleukin (IL) 17 and tissue IL-1α.

PATIENTS/METHODS: Forty-five mild to moderate acne vulgaris patients were randomly assigned into three groups. Group [A] underwent sequential application of 70% GA followed by 20% SA biweekly for three months. Group [B] underwent sequential peeling and doxycycline PO100 mg BD for 1 month followed by 100 OD for 2 months. Group [C] received oral doxycycline. Acne grading, lesion counting, and patient satisfaction were assessed. Serum samples and perilesional skin biopsies were obtained at onset and 2 weeks after finishing the treatment for assessment of serum IL-17 and tissue IL-1α.

RESULTS: All groups showed statistically significant decrease in acne grading and lesion count, increase in patient satisfaction, and decrease in serum IL-17 and tissue IL-1 α after treatment. There was no significant difference between the 3 groups before or after treatment, except regarding patient satisfaction after treatment, which was significantly higher in groups [A] and [B] than group [C] (P = .001).

CONCLUSIONS: This study recommends using sequential GA 70% and SA 20% peels in the treatment of mild or moderate acne vulgaris as a new cost-effective mode, with low-down time and potential safety, in noncompliant patients on medical therapy.

BACKGROUND: Several genes encoding transcription factors are known to be the primary cause of congenital heart disease. NKX2-5 and GATA4 were the first congenital heart disease-causing genes identified by linkage analysis. This study designed to study the association of five single-nucleotide variants of NKX2-5, GATA4, and TBX5 genes with sporadic nonsyndromic cases of a congenital cardiac septal defect in Egyptian children.

METHODS: Venous blood samples from 150 congenital heart disease children (including a ventricular septal defect, atrial septal defect, tetralogy of Fallot, and patent ductus arteriosus) and 90 apparently healthy of matched age and sex were studied by polymerase chain reaction followed by direct sequencing in order to study two single-nucleotide variants of NKX2-5 (rs2277923, rs28936670), two single-nucleotide variants of GATA4 (rs368418329, rs56166237) and one single-nucleotide variant TBX5 (rs6489957). The distribution of genotype and allele frequency in the congenital heart diseases (CHD) group and control group were analyzed.

RESULTS: We found different genotype frequencies of the two variants of NKX2-5, as CT genotype of rs2277923 was present in 58% and 36% in cases and control respectively, and TT genotype present in 6% of the cases. Also regarding missense variant rs28936670, heterozygous AG presented in 82% of the cases. Also, we observed a five prime UTR variant rs368418329, GT (42% of the cases) and GG (46% of the cases) genotypes showed the most frequent presentation in cases. While regarding a synonymous variant rs56166237, GT and GG were the most presented in cases (41.4%, 56% respectively) in contrast to control group (20%, 1.7% respectively). Also, a synonymous variant in TBX5, the distribution of genotype frequency was significantly different between the CHD group and control group. CT genotype of TBX5 -rs6489957 was found in 12 ASD, 24 VSD, six PDA, three aortic coarctation and nine fallot that represent 42% of the cases.

CONCLUSIONS: Significantly higher frequency of different allelle of five variants was observed in cases when compared to the control group, with significant risky effect for the development of septal defect. In addition to two polymorphisms of NKX2-5 (rs2277923, rs28936670) variant in the cardiac septal defect, two variants in GATA4 (rs368418329, rs56166237) and one variant in TBX5 (rs6489957) seem to have a role in the pathogenesis of congenital heart disease.

This cross-sectional comparative study aimed to compare serum L-carnitine and 25(OH)D levels between men with ED non-responding for oral sildenafil citrate and healthy volunteers. Overall, 192 men, recruited from two University Hospitals, were allocated into two equal groups of matched age; healthy potent men and men with ED non-responders for oral sildenafil citrate. Oral sildenafil citrate non-responders self-reported inadequate erectile responses after four attempts using 100 mg with the manufacturer's guidelines relative to meals, associated medications, and sexual stimulation/arousal. Exclusion criteria were: diabetes, cardiovascular disorders, beta blockers treatment, morbid obesity, thyroid disorders, post-radical prostatectomy, and hepatic/renal failure. All participants were subjected to; history taking, clinical examination, validated IIEF-5 questionnaire, estimation of serum L-carnitine by calorimetric method and serum 25(OH)D by ELISA method. Compared with potent controls, ED men non-responders for oral sildenafil citrate showed significant decreases in the mean serum L-carnitine level (16.8 ± 3.6 uM/L versus 66.3 ± 11.9 uM/L, P = 0.001), the mean serum 25(OH)D level (21.2 ± 7.1 ng/ml versus 54.6 ± 7.9 ng/mL, P = 0.001) and IIEF-5 score (7.8 ± 2.6 versus 23.9 ± 1.3). Serum L-carnitine showed significant positive correlation with IIEF-5 scores (r = 0.873, P = 001), serum 25(OH)D (r = 0.796, P = 0.001) and significant negative correlation with the age (r = -0.515, P = 0.001). Serum 25(OH)D showed significant positive correlation with IIEF-5 scores (r = 0.855, P = 0.001) and significant negative correlation with the age (r = -0.223, P = 0.005). It is concluded that normal homeostasis of serum L-carnitine and 25(OH)D play a role in male sexual health being significantly decreased in ED non-responding for oral sildenafil citrate.

This study was designed to investigate the potential effects and underlying mechanism of adipose tissue-derived mesenchymal stem cells (MSCs) on allergic inflammation compared to Montelukast as an antileukotriene drug in a rat model of allergic rhinitis (AR). The effect of MSCs was evaluated in albino rats that were randomly divided into four (control, AR, AR + Montelukast, and AR + MSCs) groups. Rats of AR group were sensitized by ovalbumin (OVA) and then challenged with daily nasal drops of OVA diluted in sterile physiological saline (50 μL/nostril, 100 mg/mL, 10% OVA) from day 15 to day 21 of treatment with/without Montelukast (1 h before each challenge) or MSCs I/P injection (1 × 10⁶ MCSs; weekly for three constitutive weeks). Both Montelukast and MSCs treatment started from day 15 of the experiment. At the end of the 5th week, blood samples were collected from all rats for immunological assays, histological, and molecular biology examinations. Both oral Montelukast and intraperitoneal injection of MSCs significantly reduced allergic symptoms and OVA-specific immunoglobulin E (IgE), IgG1, IgG2a and histamine as well as increasing prostaglandin E2 (PGE2). Further analysis revealed that induction of nasal innate cytokines, such as interleukin (IL)-4 and TNF-α; and chemokines, such as CCL11 and vascular cell adhesion molecule-1 (VCAM-1), were suppressed; and transforming growth factor-β (TGF-β) was up-regulated in Montelukast and MSCs-treated groups with superior effect to MSCs, which explained their underlying mechanism. In addition, the adipose tissue-derived MSCs-treated group had more restoring effects on nasal mucosa structure demonstrated by electron microscopical examination.

The effects of epigallocatechin-3-gallate (EGCG) and metformin single treatment have been tested against hepatocellular carcinoma (HCC). This study aimed to assess the combination effects of EGCG and metformin on proliferation and apoptosis of HepG2cells and identified new potential molecular targets. The effect of EGCG and metformin against cell proliferation in HepG2 was determined using MTT assay. Reverse transcription polymerase chain reaction was applied to examine the gene expression of cyclin D1, lncRNA-AF085935, caspase-3, survivin and VEGF. The level of protein expression of glypican-3 was assessed by western blot. In HepG2 cells, EGCG and metformin combination treatment exhibited high significant effect against tumor proliferation. It significantly reduced cyclin D1, lncRNA-AF085935, glypican-3 and promoted apoptosis through increasing caspase3 and decreasing survivin compared to control cells. Moreover, EGCG and metformin treated cells showed decreased expression levels of VEGF. Our study provided new insights of the anticarcinogenic effects of EGCG and metformin on HCC through their effects on glypican-3 and lncRNA-AF085935.

Colorectal cancer (CRC) is a major cause of death worldwide. Novel non-invasive, high diagnostic value screening test is urgently needed to improve survival rate, treatment and prognosis. Stable, small, circulating microRNA (miRNA) offers unique opportunities for the early diagnosis of several diseases. It acts as tumor oncogenes or suppressors and involve in cell death, survival, and metastasis. Communication between miRNA and carcinogenesis is critical but it still not clear and needs further investigation. The aim of our study is to evaluate the role of miR-210, miR-21, miR-126, as non-invasive diagnostic biomarkers for screening, early detection of CRC, studying their correlation with prognostic variables, and clarifying the roles of miRNAs on HIF-1α-VEGF signaling pathway. The expression of miR-210, miR-21 and miR-126 was performed using qRT-PCR in adenocarcinoma (no = 35), adenomas (no = 51), and neoplasm free controls (no = 101). Serum levels of VEGF and HIF-1α was determined by ELISA Kit. The results show that the expression of miR-210, miR-21, VEGF, HIF-1α was significantly up-regulated while that miRNA-126 was down-regulated in both adenocarcinoma and adenomas compared with controls (p < 0.001 for each). No significant difference was noted comparing patients with adenocarcinoma and adenomas. The three miRNAs correlated with VEGF, HIF-α. The miR-210 and miR-21 associated with TNM classification and clinical staging of adenocarcinoma (p < 0.001) and they show high diagnostic value with sensitivity and specificity 88.6%, 90.1% and 91.4%, 95.0% respectively. Our study revealed that circulating miR-210, miR-21 were up-regulated while miR-126 was down-regulated in CRC and adenomas patients, they all correlated with TNM staging and they had high diagnostic value. HIF-1α VEGF signaling pathways regulated by miRNAs played a role in colon cancer initiation. To the best of our knowledge, this is the first study of this miRNAs panel in CRC in our community. These data suggested that these biomarkers could be a potential novel, non-invasive marker for early diagnosis, screening and predicting prognosis of CRC. Understanding the molecular functions by which miRNAs affect cancer and understanding its roles in modulating the signaling output of VEGF might be fruitful in reducing the incidence and slowing the progression of this dark malignancy.

BACKGROUND AND AIM: Secreted protein acidic and rich in cysteine (SPARC) is a glycoprotein involved in extracellular matrix remodeling, which regulates cell growth. It could be involved in hepatic fibrogenesis related to chronic inflammations, hepatocellular carcinoma (HCC) angiogenesis, and tumor progression. We aimed to study the expressions of single nucleotide polymorphisms in the SPARC gene and their impact on susceptibility and survival of HCC patients.

METHODS: We conducted a case-control study on 200 HCC patients and 50 matched healthy controls. All patients were subjected to laboratory investigations, ultrasound, and real-time polymerase chain reaction to detect the genetic polymorphisms (rs3210714, rs11950384, and rs7719521) in the SPARC gene in the blood.

RESULTS: One hundred sixty (80%) patients were men with a mean age of 43 years. The SPARC gene showed a significant higher prevalence of rs3210714 mutation (i.e. AA or AG) and a significant lower prevalence of rs11950384 mutation (i.e. AA or AC) among HCC patients in comparison with controls (83% vs 22%, P ≤ 0.001) and (65.5 vs 86%, P = 0.005), respectively, while rs7719521 mutation did not reach significance. On univariate and multivariate analyses, elder age and having at least one copy of the mutant rs3210714 were associated with a significantly increased risk of HCC (P < 0.001 for both), whereas the presence of at least one copy of the mutant rs11950384 carried a significantly reduced risk of having HCC (P < 0.01). Overall survival did not differ significantly between any of the SPARC gene mutation groups.

CONCLUSIONS: The SPARC gene polymorphisms had a diverse impact on the susceptibility of HCC due to its ability to inhibit or promote tumor progression. SPARC gene polymorphisms were not related to survival of our HCC patients, and probably, this needs further analysis of other SPARC gene nucleotides.

Background and Objectives: The release of microvesicles (MVs) from mesenchymal stem cells (MSCs) has been implicated in intercellular communication, and may contribute to beneficial paracrine effects of stem cell-based therapies. We investigated the effect of administration of MSC-MVs on the therapeutic potential of carbon tetrachloride (CCL) induced liver fibrosis in rats.

Methods: Our work included: isolation and further identification of bone marrow MSC-MVs by transmission electron microscopy (TEM). Liver fibrosis was induced in rats by CCl4 followed by injection of prepared MSC-MVs in injured rats. The effects of MSC-MVs were evaluated by biochemical analysis of liver functions, RNA gene expression quantitation for collagen-1, transforming growth factor (TGF-), interleukin-1 (IL-1), vascular endothelial growth factor (VEGF) by real time reverse transcription PCR (RT-PCR) techniques. Finally histopathological examination of the liver tissues was assessed for all studied groups.

Results: BM-MSC-MVs treated group showed significant increase in serum albumin levels, VEGF quantitative gene expression (p<0.05), while it showed a significant decrease in serum alanine transaminase (ALT) enzyme levels, quantitative gene expression of TGF-, collagen-1, IL-1 compared to CCL fibrotic group (p<0.05). Additionally, the histopathological assessment of the liver tissues of BM-MSC-MVs treated group showed marked decrease in the collagen deposition & improvement of histopathological picture in comparison with CCL fibrotic group.

Conclusions: Our study demonstrates that BM-MSC-MVs possess anti-fibrotic, anti-inflammatory, and pro-angiogenic properties which can promote the resolution of CCL induced liver fibrosis in rats.

Long noncoding RNAs (lncRNAs), highly upregulated liver cancer (HULC), metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), lncRNA-AF085935, and lncRNA-uc003wbd have been implicated in hepatocellular carcinoma (HCC). Single-nucleotide polymorphism (SNP) in HULC and MALAT1 are associated with HCC susceptibility. However, association between these SNPs and lncRNA-AF085935 and lncRNA-uc003wbd expression and their potential clinical value in differentiating HCC from both hepatitis B virus (HBV)-infected Egyptian patients and the healthy specimens have not been explored yet. In the present study, SNPs rs7763881 in HULC and rs619586 in MALAT1 were genotyped in 70 HBV-positive HCC, 70 HBV patients, and 70 healthy controls in Egyptian population and the level of serum lncRNA-AF085935 and lncRNA-uc003wbd of all the subjects was assayed by quantitative real-time polymerase chain reaction. HULC rs7763881 AC/CC genotype was significantly associated with decreased HCC risk. Similarly, AG/GG of MALAT1 rs619586 was associated with decreased HCC risk with a borderline significance. Serum lncRNA-AF085935 and lncRNA-uc003wbd levels were upregulated in HBV-positive HCC and HBV patients vs controls and discriminated these groups by receiver operating characteristic analysis. Patients carrying AC/CC genotype of rs7763881 and AG/GG of rs619586 had lower serum lncRNA-AF085935 and lncRNA-uc003wbd levels compared with AA genotype. In conclusion, genetic variants of lncRNA HULC and lncRNA MALAT1 are associated with the decreased susceptibility to HCC in HBV-persistent carriers and are correlated with serum lncRNA-AF085935 and lncRNAuc003wbd levels, two potential noninvasive diagnostic biomarkers for HCC.

Renal injury induced by the chemotherapeutic agent methotrexate (MTX) is a serious adverse effect that has limited its use in the treatment of various clinical conditions. The antioxidant activity of extract (GB) was reported to mitigate renal injury induced by MTX. Our research was conducted to examine the nephroprotective role of GB versus MTX-induced renal injury for the first time through its impact on the regulation of phosphatidylinositol 3-kinase/protein kinase B/ mammalian target of rapamycin (PI3K/Akt/mTOR) signaling together with the renal level of TGF-β mRNA and long non-coding RNA-metastasis-associated lung adenocarcinoma transcript-1 (MALAT1) expression. A group of adult rats was intraperitoneally (ip) injected with MTX 20 mg/kg as a single dose to induce kidney injury (MTX group). The other group of rats was orally administered with GB 60 mg/kg every day for 10 days (GB+ MTX group). The MTX increased the serum creatinine and urea levels, renal TGF-β mRNA and MALAT1 expression, in addition to dysregulation of the PI3K/Akt/mTOR signaling when compared with normal control rats that received saline only (NC group). Moreover, renal damage was reported histopathologically in the MTX group. The GB ameliorated the renal injury induced by MTX and reversed the changes of these biochemical analyses. The involvement of PI3K/Akt/mTOR signaling and downregulation of TGF-β mRNA and MALAT1 renal expressions were firstly reported in the nephroprotective molecular mechanism of GB versus MTX-induced renal injury.