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1.
Article in English | MEDLINE | ID: mdl-38602541

ABSTRACT

BACKGROUND: Traumatic spinal cord injury (SCI) is the most common preventable cause of morbidity. Despite rapid advances in medicine, effective pharmacological treatment against SCI has not yet been confirmed. This study aimed to investigate the possible anti-inflammatory, antiapoptotic, and neuroprotective effects of safinamide after SCI in a rat model. METHODS: A total of 40 male Wistar albino rats were randomly divided into four groups. Group 1 underwent only laminectomy. Group 2 underwent SCI after laminectomy. In group 3, SCI was performed after laminectomy, and immediately afterward, intraperitoneal physiological saline solution was administered. In group 4, SCI was performed after laminectomy, and 90 mg/kg of safinamide was given intraperitoneally immediately afterward. Moderate spinal cord damage was induced at the level of thoracic vertebra nine (T9). Neuromotor function tests were performed and levels of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interleukin-1 beta (IL-1ß) were measured. In both serum and spinal cord tissue, immunohistochemistry and histopathology studies were also conducted. RESULTS: TNF-α, IL-1ß, and IL-6 levels were found to be significantly increased in group 2 and group 3. In group 4, these levels were statistically significantly decreased. Group 4 also exhibited significant improvement in neuromotor function tests compared to the other groups. Histopathologically, it was found that group 4 showed significantly reduced inflammation and apoptosis compared to the other groups. CONCLUSION: This study revealed that safinamide has neuroprotective effects against SCI due to its anti-inflammatory, antiapoptotic, and antioxidant activities.

2.
World Neurosurg ; 170: e558-e567, 2023 Feb.
Article in English | MEDLINE | ID: mdl-36403936

ABSTRACT

BACKGROUND: Traumatic brain injury is still an important health problem worldwide. Traumatic brain injury not only causes direct mechanical damage to the brain but also induces biochemical changes that lead to secondary nerve cell loss. In this study, we investigated the neuroprotective effect of milrinone after traumatic brain injury (TBI) in a rat model. METHODS: Forty male Wistar albino rats, were used. Rats were divided into 4 groups: 1) sham, 2) TBI, 3) TBI + Ringers, and 4) TBI + Milrinone. In group 1 (sham), only craniotomy was performed. In group 2 (TBI), TBI was performed after craniotomy. In group 3 (TBI + Ringer), TBI was performed after craniotomy and intraperitoneal Ringers solution was given immediately afterward. Group 4 (TBI + Milrinone), TBI was performed after craniotomy, and milrinone was given 1.0 mg/kg milrinone intraperitoneally directly (0.5 mg/kg milrinone intraperitoneally again 24 hours, 48 hours, and 72 hours after trauma). Tests were performed for neurological and neurobehavioral functions. Immunohistochemistry and histopathology studies were performed. RESULTS: In group 4 compared with group 2 and group 3 groups, tests for neurological functions and neurobehavioral functions were significantly better. In the milrinone treatment used in group 4, plasma and brain tissue tumor necrosis factor, 8-OH 2-deoxyguanosine , and interleukin 6 levels were significantly decreased, and increased plasma and tissue IL-10 levels were detected. Histopathological spinal cord injury and apoptotic index increased in groups 2 and 3, while significantly decreasing in group 4. CONCLUSIONS: This study shows for the first time that the anti-inflammatory, antioxidant and antiapoptotic properties of milrinone may be neuroprotective after TBI.


Subject(s)
Brain Injuries, Traumatic , Brain Injuries , Neuroprotective Agents , Animals , Rats , Male , Neuroprotective Agents/pharmacology , Neuroprotective Agents/therapeutic use , Milrinone/pharmacology , Milrinone/therapeutic use , Rats, Wistar , Brain Injuries, Traumatic/drug therapy , Brain Injuries, Traumatic/pathology , Brain Injuries/pathology , Brain/pathology , Disease Models, Animal
3.
Growth Factors ; 40(3-4): 153-162, 2022 08.
Article in English | MEDLINE | ID: mdl-35867635

ABSTRACT

Ovarian cancer (OC) is clinically important because it is diagnosed late and has metastasis when it is diagnosed. Mortality risk increases 2.75 times in the presence of lymph node (LN) metastasis. During metastasis, many molecules including BMPs originated from stroma, and tumor cells participate through transcription factors and integrins for cytoskeleton regulation during cell migration. We hypothesized an inverse correlation between BMP2 and BMP7 along with changes in ZEB2, and integrin α5ß1 in high-grade OCs in relation to LN metastasis. The BMP2 immunoreactivity was strong along with strong ZEB2 and weak integrins' immunoreactivity in samples with LN metastasis. Strong immunoreactivity of BMP7 was accompanied by strong immunoreactivity of integrins in the samples without LN metastasis. Study results showed BMP2's strong positive immunoreactivity and weak BMP7 immunoreactivity in tumor cells with a significantly weak inverse correlation. This inverse correlation should be considered as both BMPs have different effects in the window of cancer progression and invasion.


Subject(s)
Carcinoma , Ovarian Neoplasms , Zinc Finger E-box Binding Homeobox 2 , Carcinoma/metabolism , Carcinoma/pathology , Cell Movement , Female , Humans , Integrins , Lymphatic Metastasis , Ovarian Neoplasms/metabolism , Ovarian Neoplasms/pathology , Zinc Finger E-box Binding Homeobox 2/genetics
4.
Lasers Surg Med ; 54(2): 268-280, 2022 02.
Article in English | MEDLINE | ID: mdl-34289510

ABSTRACT

OBJECTIVES: Unpredictability with the final volume and viability of the graft are the major concerns in fat grafting. An experimental study was conducted to increase graft retention using photobiomodulation (PBM) with polychromatic light in near-infrared region (600-1200 nm) by utilizing its stimulatory effects on angiogenesis, neovascularization, adipocyte viability, and anti-inflammatory properties. METHODS: A total of 24 rats were divided into four groups (n = 6) according to the applied polychromatic light protocol to the recipient site (none, before fat transfer, after fat transfer, and combined). In all groups, inguinal fat pad was excised, measured for volume and weight, and transferred to the dorsum of the rat. At the end of the experiment, fat grafts were harvested from the recipient site for volume and weight measurements, histological, and immunohistochemical evaluation. RESULTS: Intergroup comparison revealed that fat graft retention regarding weight and volume, was significantly superior in Group IV (p = 0.049 and p = 0.043, respectively), which polychromatic light was applied both before and after transfer of the graft. Hematoxylin-eosin and Masson's trichrome stained sections showed absence of necrosis, fibrosis, inflammation, cyst formation, and increased vascularization of both inner and outer zones of the grafts in Group IV. Also, immunohistochemical staining scores for perilipin (indicator for adipocyte viability), CD31 and VEGF (indicators for angiogenesis and neovascularization) were significantly higher (p < 0.001). Ki67 scores were significantly lower in this group because of anti-inflammatory environment (p < 0.001). CONCLUSIONS: Application of PBM to the recipient site before and after fat transfer improved outcomes in rats at 56 day after fat grafting by means of volume retention, increased neovascularization and adipocyte viability and reduced necrosis, fibrosis and inflammation.


Subject(s)
Adipocytes , Graft Survival , Adipose Tissue , Animals , Inflammation , Necrosis , Neovascularization, Physiologic , Rats
5.
Neurochem Int ; 148: 105079, 2021 09.
Article in English | MEDLINE | ID: mdl-34048846

ABSTRACT

Dental pulp stem cells (DPSCs) have a high capacity to differentiate into the neuronal cell lineage. Meanwhile, both Hippo signaling and melatonin are key regulators in neuronal differentiation of neuronal progenitor cells. Recently emerging evidences suggest the possible interaction between melatonin and Hippo signaling in different cell lines. But underlying mechanisms involved in the initiation or progression of neurogenic differentiation in DPSCs through this connection need to be explored. Therefore, the scope of this study is to investigate the effect of melatonin on Hippo signaling pathway through the expression of its downstream effector (YAP/p-YAPY357) after the neuronal differentiation of DPSCs. In regard with this, DPSCs were incubated with growth and dopaminergic neuronal differentiation medium with or without melatonin (10 µM) for 21 days. The morphological changes were followed by phase contrast microscopy and differentiation of DPSCs was evaluated by immunofluorescence labelling with NeuN, GFAP, and tyrosine hydroxylase. Furthermore, we evaluated the presence of neural progenitor cells by nestin immunoreactivity. Hippo signaling pathway was investigated by evaluating the immunoreactivity of YAP and p-YAPY357. Our results were also supported by western-blot analysis and SOX2, PCNA and caspase-3 were also evaluated. The positive immunoreactivity for NeuN, tyrosine hydroxylase and negative immunoreactivity for GFAP showed the successful differentiation of DPSCs to neurons, not glial cells. Melatonin addition to dopaminergic media induced tyrosine hydroxylase and decreased significantly nestin expression. The expressions of PCNA and caspase-3 were also decreased significantly with melatonin addition into growth media. Melatonin treatment induced phosphorylation of YAPY357 and reduced YAP expression. In conclusion, melatonin has potential to induce neuronal differentiation and reduce the proliferation of DPSCs by increasing phosphorylation of YAPY357 and eliminating the activity of YAP, which indicates the active state of Hippo signaling pathway.


Subject(s)
Dental Pulp/cytology , Hippo Signaling Pathway/drug effects , Melatonin/pharmacology , Neurogenesis/drug effects , Stem Cells/cytology , Cell Differentiation/drug effects , Cell Differentiation/physiology , Cell Lineage/drug effects , Cell Lineage/physiology , Cells, Cultured , Dental Pulp/metabolism , Dopaminergic Neurons/drug effects , Dopaminergic Neurons/metabolism , Humans , Neurogenesis/physiology
6.
Cell Tissue Bank ; 22(4): 719-726, 2021 Dec.
Article in English | MEDLINE | ID: mdl-33914204

ABSTRACT

Granulosa cells are the cell population who have an increasing importance in the female genital system and reproduction. Thus, nowadays in vitro studies to address these cells are also gaining importance and attracts researcher's attention. The aim of our study is to develop a more feasible, low-cost granulosa cell isolation and culture method compared to methods defined so far. Granulosa cells were isolated from follicular fluids obtained from both healthy women donors (n = 19) and polycystic ovary syndrome (n = 15) applied to in vitro fertilization treatment process. Granulosa cells were isolated by using Lymphosep® separation fluid that was not used for this purpose before. The isolated cells were cultured in suitable culture dishes with a mixture of BIO-AMFTM-1 and DMEM/F12 in the first seeding and only complete DMEM/F12 in the following feeds. Complete medium contains only 5% fetal calf serum, 4% L-glutamine and 1% penicillin-streptomycin-amphotericin. The new methods we have developed in granulosa cell isolation and in vitro culture have been successful. Reduction in supplement types and amount; improved the proliferation rate of the granulosa cells in culture. Our new methods of isolation and cell culture for granulosa cells from healthy women, have been also successful in samples of polycystic ovarian patients. With these developed methods, granulosa cells, which belong to humans and have an important role in the ovary, could be isolated and subsequently be maintained to reproduce (proliferate) more easily and cheaper.


Subject(s)
Granulosa Cells , Polycystic Ovary Syndrome , Cell Culture Techniques , Cells, Cultured , Female , Follicular Fluid , Humans
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