Acceleration of Wound Healing in Diabetic Rats through a Novel 3D Organo-Hydrogel Nanocomposite of Polydopamine/TiO2 Nanoparticles and Cu (PDA-TiO2@Cu).

BACKGROUND: Diabetic wound represents a serious issue with a substantial impact and an exceptionally complex pathology affecting patients' mental health and quality of life. So, we have developed a novel 3D organo-hydrogel nanocomposite of polydopamine/TiO2 nanoparticles and cu (PDA-TiO2@Cu) and examined its efficacy in diabetic wound healing. METHODS: Forty-five adult male albino rats were divided into normal control rats (non-diabetic rats with non-treated skin wounds), diabetic control rats (diabetic rats with non-treated skin wounds), and organo-hydrogel-treated rats (diabetic wounds treated with topically applied organo- hydrogel once daily). Macroscopic changes of the wound were observed on days 0, 3, 5, 7, and 10 to measure wound diameters. Skin specimens from the wound tissue were taken on days 3, 7, and 10, respectively, and examined histologically and immunohistochemically. Also, the gene expressions of collagen I, Matrix Metalloproteinase-9 (MMP-9), and Epidermal Growth Factor (EGF), and levels of Interleukin 6 (IL-6) and Superoxide Dismutase (SOD) were assessed. RESULTS: Our observed results indicated that the developed patch significantly accelerated the healing time compared to the normal control and diabetic control groups. Moreover, the patchloaded group revealed complete re-epithelization and a highly significant increase in the mean area % of CD31 immunostaining on day 7. The organo-hydrogel-loaded group displayed a significant decrease in gene expression of MMP-9 and a significant increase in gene expression of EGF and collagen I. Additionally, the organo-hydrogel-loaded group exhibited a significant decrease in levels of IL-6 and a significant increase in levels of SOD, compared to the normal diabetic control groups. CONCLUSION: The organo-hydrogel can be used for treating and decreasing the healing period of diabetic wounds.

The Possible Protective Effect of Taurine on Bisphenol: Induced Structural Changes on the Cerebral Cortex of Rats: Histological and Immunohistochemical Study.

INTRODUCTION: Bisphenol A (BPA) is a chemical compound that has been used in many industries, such as paints and dental sealants. Taurine is a semi-essential amino acid with antioxidant, anti-inflammatory, and anti-apoptotic actions. AIM: This study aimed to evaluate the possible protective effect of taurine on BPA-induced structural changes in the cerebral cortex of rats using histological and immunohistochemical methods. MATERIALS AND METHODS: 35 Wistar rats (180-200 gm) were divided into control: 10 rats; Group I: 5 rats received corn oil (0.5 mL/day); Group II (Bisphenol low dose; BPAL): 5 rats received a low dose of BPA (25 mg/kg/three times/week); Group III (Bisphenol high dose; BPAH): 5 rats received a high dose of BPA (100 mg/kg/ three times/week; Group IV: (BPAL + taurine): 5 rats received taurine 100 mg/kg/day and BPAL (25 mg/kg/three times/week); Group V: (BPAH + taurine): 5 rats received taurine 100mg/kg/day and BPH (100 mg/kg/ three times/week). RESULTS: BPAL& BPAH groups showed significant dose-dependent histological changes of the neuropil, pyramidal, and neuroglial cells at H&E stained sections, significantly increased GFAP, caspase-3 immunohistochemical reaction with cells positive for Ki67 with many mitotic figures. BPAL + taurine and BPAH + taurine groups showed amelioration of the previously mentioned results. CONCLUSION: Taurine ameliorated the structural changes induced by BPA in the cerebral cortex of rats.

Metformin improves d-galactose induced premature ovarian insufficiency through PI3K-Akt-FOXO3a pathway.

PURPOSE: Metformin (MET), a first-line treatment for type 2 diabetes mellitus, restores ovarian function in women with polycystic ovary syndrome. MET has been shown to increase the rate of success for in vitro fertilization when utilized in assisted reproductive technologies. This study was designed to examine the impact of MET on ovarian function and fertility in a mouse model of galactose-induced premature ovarian insufficiency (POI). We further investigated the underlying mechanisms. MATERIALS AND METHODS: Female mice were divided into 4 groups: saline, d-galactose, d-galactose â€‹+ â€‹MET, and MET. Body weight, ovarian index, and fertility were assessed. The hormonal profile was done. Advanced glycation end products (AGEPs), receptor for advanced glycation end products (RAGE), phosphoinositide 3-kinase (PI3K), protein kinase B (Akt), forkhead box O3a (FOXO3a) expression were measured. Ovarian follicle counting and morphology were analyzed. Immunohistochemistry of cleaved caspase-3 expression was performed. RESULTS: Our findings demonstrated that MET reversed irregularities in the estrus cycle, enhanced the ovarian index, and improved the abnormal levels of hormones and AGEs induced by d-galactose. Furthermore, the expression levels of PI3K, Akt, FOXO3a, and RAGE were upregulated with d-galactose. However, MET attenuated their expression levels. The primordial follicles ratio was improved, whereas atretic follicles and apoptotic-related cleaved caspase-3 expression were decreased in the d-galactose â€‹+ â€‹MET group compared to the d-galactose group. CONCLUSION: This study demonstrates that MET partially rescued ovarian dysfunction and apoptosis induced by d-galactose via a mechanism involving PI3K-Akt-FOXO3a pathway. Our finding proposed that MET may be a promising alternative treatment for POI.

Magnesium Supplementation Alleviates the Toxic Effects of Silica Nanoparticles on the Kidneys, Liver, and Adrenal Glands in Rats.

Concerns regarding the possible hazards to human health have been raised by the growing usage of silica nanoparticles (SiNPs) in a variety of applications, including industrial, agricultural, and medical applications. This in vivo subchronic study was conducted to assess the following: (1) the toxicity of orally administered SiNPs on the liver, kidneys, and adrenal glands; (2) the relationship between SiNPs exposure and oxidative stress; and (3) the role of magnesium in mitigating these toxic effects. A total of 24 Sprague Dawley male adult rats were divided equally into four groups, as follows: control group, magnesium (Mg) group (50 mg/kg/d), SiNPs group (100 mg/kg/d), and SiNPs+ Mg group. Rats were treated with SiNPs by oral gavage for 90 days. The liver transaminases, serum creatinine, and cortisol levels were evaluated. The tissue malondialdehyde (MDA) and reduced glutathione (GSH) levels were measured. Additionally, the weight of the organs and the histopathological changes were examined. Our results demonstrated that SiNPs exposure caused increased weight in the kidneys and adrenal glands. Exposure to SiNPs was also associated with significant alterations in liver transaminases, serum creatinine, cortisol, MDA, and GSH. Additionally, histopathological changes were significantly reported in the liver, kidneys, and adrenal glands of SiNPs-treated rats. Notably, when we compared the control group with the treated groups with SiNPs and Mg, the results revealed that magnesium could mitigate SiNPs-induced biochemical and histopathologic changes, confirming its effective role as an antioxidant that reduced the accumulation of SiNPs in tissues, and that it returns the levels of liver transaminases, serum creatinine, cortisol, MDA, and GSH to almost normal values.

Modulatory Role of Autophagy in Metformin Therapeutic Activity toward Doxorubicin-Induced Nephrotoxicity.

Doxorubicin (DOX) is a frequent chemotherapeutic drug used to treat various malignant tumors. One of the key factors that diminish its therapeutic importance is DOX-induced nephrotoxicity. The first-line oral antidiabetic drug is metformin (Met), which also has antioxidant properties. The purpose of our study was to investigate the underlying molecular mechanisms for the potential protective effects of Met on DOX-triggered nephrotoxicity. Four animal groups were assigned as follows; animals received vehicle (control group), 200 mg/kg Met (Met group), DOX 15 mg/kg DOX (DOX group), and a combination of DOX and Met (DOX/Met group). Our results demonstrated that DOX administration caused marked histological alterations of widespread inflammation and tubular degeneration. Notably, the DOX-induced dramatic up-regulation of the nuclear factor-kappa B/P65 (NF-κB/P65), microtubule-associated protein light chain 3B (LC3B), neutrophil gelatinase-associated lipocalin (NGAL), interleukin-1beta (IL-1ß), 8-hydroxy-2' -deoxyguanosine (8-OHdG), and Beclin-1 in renal tissue. A marked increase in the malondialdehyde (MDA) tissue level and a decrease in the total antioxidant capacity (TAC) were also recorded in DOX-exposed animals. Interestingly, Met could minimize all histopathological changes as well as the disruptions caused by DOX in the aforementioned measures. Thus, Met provided a workable method for suppressing the nephrotoxicity that occurred during the DOX regimen via the deactivation of the Beclin-1/LC3B pathway.

Palliative effect of Moringa olifera-mediated zinc oxide nanoparticles against acrylamide-induced neurotoxicity in rats.

Repeated acrylamide (ACR) exposure in experimental animals and humans causes variable degrees of neuronal damage. Because of its unique features, several green synthesized nanomaterials are explored for neuromodulatory activity. Hence, this study investigated the effect of green synthesized zinc oxide nanoparticles using Moriga olifera leaves extract (MO-ZnONP) against acrylamide (ACR)-induced neurobehavioral and neurotoxic impacts in rat. Forty male Sprague Dawley rats were distributed into four groups orally given distilled water, MO-ZnONP (10 mg/kg b.wt), ACR (20 mg/kg b.wt), or MO-ZnONP + ACR for 60 days. Gait quality and muscular, motor, and sensory function were assessed. Acetylcholinesterase (AChE), dopamine, catalase, malondialdehyde (MDA), and Zn brain contents were determined. Brain histopathology and immunohistochemical localization of the amyloid-ß protein and abnormal Tau were performed. The results revealed that MO-ZnONP significantly reduced ACR-induced sensory dysfunctions, hind limb abnormality, and motor deficits. Additionally, the ACR-induced increase in dopamine and AChE were significantly supressed by MO-ZnONP. Besides, MO-ZnONP significantly restored catalase and Zn content but reduced increased MDA brain content resulting from ACR. Furthermore, the ACR-induced neurodegenerative changes and increased amyloid-ß and phosphorylated Tau immunoexpression was significantly abolished by MO-ZnONP. Conclusively, MO-ZnONP could be used as a biologically effective compound for mitigating ACR's neurotoxic and neurobehavioral effects.

Topical and oral applications of Aloe vera improve healing of deep second-degree burns in rats via modulation of growth factors.

INTRODUCTION: Burn injuries are underappreciated injuries that cause significant morbidity and mortality. Burn injuries, especially severe burns, trigger immunological and inflammatory responses, metabolic abnormalities, and distributive shock, all of which can be extended to multiple organ failures. Aloe vera (A. vera) has been exploited for its medicinal properties for centuries. The goal of the present study is to examine the therapeutic effect of topical and oral administration of A. vera against deep second-degree burn in rats. MATERIALS AND METHODS: skin burn was created on the back of rats, and wound healing was assessed within the three examined groups; control, topical A. vera and oral A. vera throughout 30 days. Wound tissues were examined histologically, immunohistochemically for the expression of transforming growth factor beta-1 (TGF-ß1), peroxiredoxin (Prdx6), and mRNA abundance of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) was assessed. RESULTS: Our finding showed acceleration of wound contraction with both topical and oral A. vera administration. Maturation of granulation tissues was seen in both A. vera-supplemented groups. The topical application of A. vera revealed marked remodelling of the granulation tissues and higher expression levels of TGF-ß1, VEGF, bFGF, and Prdx6 in comparison with control and oral A. vera groups (P < 0.001). CONCLUSION: Both oral and topical applications of A. vera have beneficial effects in deep second-degree burn wound healing by boosting the growth factors and antioxidant status of skin tissue. The topical treatment was more efficient in accelerating wound healing and hence could be used efficiently to treat second-degree burns.

Mesenchymal stem-cells' exosomes are renoprotective in postmenopausal chronic kidney injury via reducing inflammation and degeneration.

Chronic kidney disease (CKD) is an important global disease its rates are increasing worldwide. CKD is caused by injuries to kidney tissue that exceeds the rate of regeneration, which with time lead to irreversible renal damage and CKD become evident. In females, diminished estrogen supply in the postmenopausal period is associated with greater risk for developing CKD. In this study we isolated exosomes from bone marrow mesenchymal stem/stromal cells (BM-MSCs) and tested their therapeutic effects on post-menopause CKD (PM-CKD) and compared their effects with BM-MSCs. The menopause model was achieved by bilateral ovariectomy in 8-months-old female albino rats, then no treatment, 2 million BM-MSCs or 100 µg of exosomes (Exo) was given intravenously in tail vein to ovariectomized rats and the study continued for 8 weeks post-ovariectomy. Changes in weight, urine volume, urine protein content, kidney function biochemical parameters (creatinine and BUN), Kidney oxidative stress (MDA), kidney antioxidant parameters (SOD, GPx and CAT), histopathological changes, immunohistochemical expression of KIM-1 and, finally, genes related to renal damage (peroxiredoxin-3, KIM-1 and ICAM-1) and inflammation (TNF-α, Cox2 and IL-6) were recorded for all study groups. Post-ovariectomy there was an increased body weight, drastic reduction of estrogen and progesterone levels, reduced urine output, increased urinary protein excretion, elevated serum creatinine and BUN, increased MDA and reduced GPx SOD, and CAT in kidney tissue, chronic inflammation, degenerative and fibrotic lesions in histopathological examination, high expression of KIM-1 immunohistochemically and changes in gene expression analyses all pointing to the development of CKD in the study rats. In the PM-CKD groups receiving BM-MSCs or Exo, the whole chronic inflammatory picture was completely reversed towards a much normal kidney structure and function. The improvements were more observable with Exo compared to BM-MSCs. Overall, our results show for the first time that exosomes isolated from BM-MSCs are more potent in reducing chronic inflammatory changes in the kidney of postmenopausal females compared to the cell-based approach using BM-MSCs. Therefore, MSCs-derived exosomes are a promising therapeutic approach for preserving postmenopausal kidney structure and function and, subsequently, should improve the quality of life of postmenopausal females.

Lycopene ameliorates the effect of Aroclor 1254 on morphology, proliferation, and angiogenesis of the thyroid gland in rat.

Aroclor 1254 is a mixture of polychlorinated biphenyls that are reported to disrupt thyroid hormone homeostasis, yet little is known on its effect on thyroid gland microarchitecture. Lycopene is a commonly used potent antioxidant. This study is a biochemical, histological, and immunohistochemical assessment of the effect of Aroclor 1254 on the morphology, proliferation, and angiogenesis of the thyroid gland in rat and to evaluate the possible ameliorating role of lycopene. Twenty-four adult male albino rats were divided into 4 groups; Control, lycopene-treated (4 mg/kg/day orally for 30 days), Aroclor 1254-treated (2 mg/kg/day intraperitoneally for 30 days), and lycopene & Aroclor 1254-treated group. Serum thyroid hormones, thyroid-stimulating hormone (TSH), and tissue malondialdehyde (MDA) were quantified. Thyroid specimens were processed for histological staining with hematoxylin and eosin, periodic acid-Schiff, and Mallory's trichrome stains as well as immunohistochemical staining for detection of calcitonin, Ki67, and VEGF. In this study, Aroclor 1254-treated animals recorded a significant decline in both serum T3 and T4 coupled with a significant elevation in both TSH and tissue MDA. Histological sections showed small irregular follicles with the formation of hyperplastic and micro follicles. Some follicular and parafollicular cells depicted nuclear and cytoplasmic alterations associating with scanty or absent colloid in addition to signs of inflammation and fibrosis. A significant upregulation in the immunohistochemical expression of calcitonin, Ki67, and VEGF was recorded. Lycopene co-treatment successfully reinstated the values of most studied parameters and retrieved a near-control thyroid morphology. In conclusion, Aroclor 1254 impacted the thyroid hormone homeostasis, morphology, proliferation, and angiogenesis of the thyroid gland in rat, while lycopene efficiently ameliorated these adverse effects.

Heat shock protein 47 as indispensible participant in liver fibrosis: Possible protective effect of lactoferrin.

Lactoferrin (LF) was previously suggested to have a protective effect against liver fibrosis by preventing hepatic stellate cells (HSCs) activation. The effect of LF on heat shock protein 47 (HSP47) has not yet been studied so this study was designed to investigate LF effect on HSP47 as a potential target for management of liver fibrosis and comparing it with silymarin (SM) in a thioacetamide (TAA)-induced liver fibrosis model. Rats were divided into four groups; normal control, TAA (TAA-treated), LF (LF + TAA-treated), and SM (SM + TAA-treated). After 6 weeks, both LF and SM improved the grade of cirrhosis, reduced collagen fibers deposition, inactivated HSCs, significantly decreased elevated liver enzymes, HSP47, hydroxyproline content, transforming growth factor-beta 1, matrix metalloproteinase-2, 8-hydroxydeoxyguanosine, malondialdehyde, nitric oxide levels and the percentage of alpha smooth muscle actin positive HSCs compared with TAA group. Moreover, LF significantly increased the total antioxidant capacity compared with TAA group. It could be concluded that LF is a promising antifibrotic drug and could be considered as one of the HSP47 inhibitors but SM is still more potent. © 2018 IUBMB Life, 70(8):795-805, 2018.

Gastroprotective effects of montelukast and Nigella sativa oil against corticosteroid-induced gastric damage: they are much more than antiasthmatic drugs.

Corticosteroids are used to treat a variety of diseases like bronchial asthma. However, long-term corticosteroids have a gastric ulcerogenic potential. Montelukast (MTK) and Nigella sativa oil (NSO) are used in treatment of bronchial asthma. Previous studies showed that MTK and NSO had gastroprotective effects in other models of gastric ulcer. The present study assesses synergistic gastroprotective effects of both drugs in dexamethasone (DXM)-induced gastric damage. Fifty male rats were divided into 5 groups: normal control (I), DXM group (II), MTK + DXM group (III), NSO + DXM group (IV), MTK + NSO + DXM group (V). After 7 days, stomachs were removed for biochemical analysis and histological examinations. Significant increases in malondialdehyde (MDA) level, superoxide dismutase (SOD) activity, myeloperoxidase (MPO) activity, and proliferating cell nuclear antigen (PCNA) positive cells, with significant decreases in mucus secretion were detected in DXM-treated group compared with group I. Meanwhile, significant decreases of MDA level, MPO activity, and PCNA positive cells and significant increases in mucus secretion were detected in treated groups compared with group II. SOD activity significantly decreased in group V compared with group II. We could conclude that administration of either MTK or NSO or both with DXM counteracts DXM-induced gastric lesions.