Background/Aims: Impaired wound healing is considered to be one of the most serious complications associated with diabetes as it significantly increases the susceptibility of patients to infection. Propolis is a natural bee product used extensively in foods and beverages that has significant benefits to human health. In particular, propolis has antioxidant, anti-inflammatory and analgesic effects that could be useful for improving wound healing. In this study, we investigated the effects of topical application of propolis on the healing and closure of diabetic wounds in a streptozotocin (STZ)-induced type I diabetic mouse model. Methods: Sixty male mice were distributed equally into 3 experimental groups: group 1, non-diabetic control mice; group 2, diabetic mice; and group 3, diabetic mice treated daily with a topical application of propolis. Results: We found that diabetic mice exhibited delayed wound closure characterized by a significant decrease in the levels of TGF-β1 and a prolonged elevation of the levels of inflammatory cytokines (IL-1β, IL-6 and TNF-α) and MMP9 in wound tissues compared with control non-diabetic mice. Moreover, the wound tissues of diabetic mice showed a marked reduction in the phosphorylation of Smad2 and Smad3 as well as a marked reduction in collagen production. Interestingly, compared with untreated diabetic mice, topical application of propolis significantly enhanced the closure of diabetic wounds and decreased the levels of IL-1β, IL-6, TNF-α and MMP9 to near normal levels. Most importantly, compared with untreated diabetic mice, the treatment of diabetic mice with propolis significantly enhanced the production of collagen via the TGF-β1/Smad2,3 signaling axis in wounded tissues. Conclusion: Our findings reveal the molecular mechanisms underlying the improved healing and closure of diabetic wounds following topical propolis application.
Gaucher's disease (GD) is an autosomal recessive genetic disorder that results from pathogenic mutations of GBA gene encoding the enzyme glucocerebrosidase (acid β-glucosidase). Of the approximately 300 mutations associated with GD, 4 accounts for the majority of mutations seen in GD patients: N370S, L444P, 84 GG and IVS2+1. Establishing and providing, clinical and molecular backgrounds of pediatric patients with GD in Upper Egypt. The present study is a cross sectional study, carried out on 26 pediatric patients with GD. They were recruited from the pediatric outpatient clinics and inpatients Pediatric departments of Assiut and Qena University hospitals, Upper Egypt. Clinical evaluation and mutation analysis using commercially available strip assay kit after PCR amplification of the target gene were done for all included GD patients. Consanguinity between patients' parents was present in 73.1% of the included patients. 76.9% of included patients were of type 1 GD, while 23.1% were of type 3 GD and none of our patients was classified as type 2 GD. The main frequent clinical presentations of GD in this study were hepatosplenomegaly (88.5%); pallor (76.9%); abdominal distension (61.5%) and musculoskeletal involvement (37.1%). Neurological abnormalities of type 3 GD included in this study were squint, seizures and delayed mental development. Five different genotypes were detected, homozygous for the mutation L444P, homozygous for the mutation N370S, heterozygous for the mutations N370S and rec Ncil, heterozygous for IVS2 +1 and rec NciI, heterozygous for L444P and IVS2 +1. Non-neuropathic type 1 and type 3 GD were the only clinical types found in the present study. The most common mutant alleles found in this study were L444P and N370S.
Hepatitis E virus (HEV) causes about 14 million infections with 300,000 deaths and 5,200 stillbirths worldwide annually. Extrahepatic manifestations are reported with HEV infections, such as renal, neurological, and hematological disorders. Recently, we reported that stool-derived HEV-1 replicates efficiently in human monocytes and macrophages in vitro. However, another study reports the presence of viral RNA but no evidence of replication in the PBMCs of acute hepatitis E (AHE) patients. Therefore, the replication of HEV in PBMCs during AHE infection is not completely understood.PBMCs were isolated from AHE patients (n = 17) enrolled in Assiut University Hospitals, Egypt. The viral load, positive (+) and negative (-) HEV RNA strands and viral protein were assessed. The gene expression profile of PBMCs from AHE patients was assessed. In addition, the level of cytokines was measured in the plasma of the patients.HEV RNA was detected in the PBMCs of AHE patients. The median HEV load in the PBMCs was 1.34 × 103 IU/ml. A negative HEV RNA strand and HEV open reading frame 2 protein were recorded in 4/17 (23.5%) of the PBMCs. Upregulation of inflammatory transcripts and increased plasma cytokines were recorded in the AHE patients compared with healthy individuals with significantly elevated transcripts and plasma cytokines in the AHE with detectable (+) and (-) RNA strands compared with the AHE with the detectable (+) RNA strand only. There was no significant difference in terms of age, sex, and liver function tests between AHE patients with detectable (+) and (-) RNA strands in the PBMCs and AHE patients with the (+) RNA strand only.Our study shows evidence for in vivo HEV persistence and replication in the PBMCs of AHE patients. The replication of HEV in the PBMCs was associated with an enhanced immune response, which could affect the pathogenesis of HEV.
Abstract Lung cancer remains incurable; therefore, novel therapeutical approaches are of great demand. This study was designed to investigate the effectiveness of cisplatin nanoparticles combined with vitamin‐D 3 on urethane‐induced early lung cancer in rats and to clarify the underlying signaling mechanisms. Early lung cancer was induced in male Wistar rats by urethane. Rats were divided into six groups: I‐control, II‐cancer untreated, III‐cancer + free cisplatin, IV‐cancer + cisplatin nanoparticles, V‐cancer + free cisplatin + vitamin‐D 3 , VI‐cancer + cisplatin nanoparticles + vitamin‐D 3 . Inflammation, proliferation, and apoptosis were evaluated together with the levels of tumor marker CK‐19 along with histological assessment. Treatment of lung cancer with either free or nanoparticles of cisplatin alone demonstrated significant suppression in the expression of inflammatory, anti‐apoptotic and tumor markers compared to rats with lung cancer. Moreover, vitamin‐D 3 supplementation with either cisplatin forms lead to a further decrease of all markers, markedly with cisplatin nanoparticles. The present study shows the synergistic effect of cisplatin‐nanoparticles combined with vitamin‐D 3 as a new therapy regimen against lung cancer. Further studies with larger sample sizes and longer duration are needed to confirm these results.
Endometriosis is a chronic debilitating inflammatory condition characterized by the presence of endometrial tissues outside the uterine cavity. Pelvic soreness and infertility are the usual association. Due to the poor effectiveness of the hormone therapy and the high incidence of recurrence following surgical excision, there is no single effective option for management of endometriosis. Mesenchymal stem cells (MSCs) are multipotent stromal cells studied for their broad immunoregulatory and anti-inflammatory properties; however, their efficiency in endometriosis cases is still a controversial issue. Our study aim was to evaluate whether adipose tissue-derived MSCs (AD-MSCs) could help with endometriosis through their studied anti-inflammatory role.Female Wistar rats weighting 180 to 250 g were randomly divided into two groups: group 1, endometriosis group; established by transplanting autologous uterine tissue into rats' peritoneal cavities and group 2, stem cell treated group; treated with AD-MSCs on the 5th day after induction of endometriosis. The proliferative activity of the endometriosis lesions was evaluated through Ki67 staining. Quantitative estimation of interferon γ, tumor necrosis factor-α, interleukin (IL)-6, IL-1β, IL-10, and transforming growth factor β expression, as well as immunohistochemical detection of CD68 positive macrophages, were used to assess the inflammatory status.The size and proliferative activity of endometriosis lesions were significantly reduced in the stem cell treated group. Stem cells efficiently mitigated endometriosis associated chronic inflammatory reactions estimated through reduction of CD68 positive macrophages and the expression of the proinflammatory cytokines.Stem cell therapy can be considered a novel remedy in endometriosis possibly through its anti-inflammatory and antiproliferative properties.
Uterine Leiomyoma (UL) is a major source of gynecologic and reproductive dysfunction in females of reproductive age. They are highly fibrotic tumors with evident disturbance of the mechano-transduction molecules. Ezrin acts as a dynamic linkage between the cytoskeleton and the membrane-associated proteins known to be dysregulated in tumorigenesis. Aim of the study: The current study aimed to profile the expression of ezrin, phospho-ezrin, and their upstream effector molecules; RhoA and ROCK1 in UL, their adjacent tissues, and control myometrium. Materials and Methods: Ezrin, phospho-ezrin, RhoA and ROCK1 mRNA and proteins were assayed in the tissue lysate of fibroid, and adjacent myometrium of 43 pre-menopausal women with symptomatic UL and 18 non-fibroid myometrium as a control group. Results: Tissue levels of ezrin, phospho-ezrin, RhoA and Rock in fibroid and adjacent tissues were higher compared to the control tissue. Moreover, the levels of phospho-ezrin and total RhoA proteins showed higher levels in fibroid compared to adjacent tissues. Phospho-ezrin and ROCK1 mRNA correlated positively with both uterine and fibroid size. Conclusion: Ezrin, phospho-ezrin, and RhoA-ROCK upregulation in leiomyoma and its adjacent myometrium signify the central role of ezrin and its upstream and downstream effector on the pathogenesis and progression of UL.