Does the use of low-molecular-weight heparin during pregnancy change the expression of PD-1 and PDL-1 in women with recurrent pregnancy loss?

Objective: The programed cell death gene-1 ligand (PDL-1) is expressed by villous syncytiotrophoblasts, cytotrophoblasts, and fetal cells in close contact with maternal tissue and blood. Programmed cell death gene-1 (PD-1) and the PDL-1 pathway cooperate with human leucocyte antigen-G (HLA-G), expressing intermediate trophoblastic cells and syncytiotrophoblasts to inhibit the function of activated T-cells. With this mechanism, the immunosuppressive microenvironment protects the placenta. This study investigated changes in PD-1 and PD-L1 gene expression in patients with a history of recurrent pregnancy loss (RPL). Materials and Methods: Sixty patients participated in the study and were divided into three groups. Group 1 (G1): healthy pregnancy, G2: RPL but not low-molecular-weight heparin (LMWH), and G3: RPL and LMWH. PD-1 gene expression in placental tissue samples was measured by reverse-transcriptase polymerase chain reaction and PD-L1 Elisa assay, and the study was supported by histopathology. Results: The PD-L1 value decreased significantly in G2. A significant difference was observed between the groups in PD-1 gene expression levels in G1 and G2. It was observed that vascularization increased and the villi structures intensified in G3. In G2, there was villus dysplasia in the placenta, enlargement in the intervillous region, and fibrin deposition. It was observed that the villi structures in G3 returned to a morphology similar to that of G1. Conclusion: T-cells are activated in patients using LMWH, and a new therapeutic strategy can be developed to prevent pregnancy loss by targeting the PD-1 pathway.

The effect of platelet-rich plasma on intra-abdominal adhesions in rabbit uterine horn model.

OBJECTIVE: This study was carried out to investigate the effect of autologous platelet-rich plasma (PRP) on intra-abdominal adhesion at the cesarean section incision line in the uterus. MATERIAL AND METHODS: As experimental animals 16 white New Zealand rabbits, 5-months-old, unmated, were used. Animals were divided into two groups the control group and PRP application group. In each group, a transverse incision was made to the uterus to mimic the cesarean section and sutured. Relaparotomy was performed 21 days after the first operation. RESULTS: When the groups were evaluated in terms of inflammation, there was a significant difference between the two groups. When the groups were evaluated in terms of Mason's Trichrome staining and fibrosis, There was a significant difference between groups. When the groups were evaluated in terms of vascular endothelial growth factor-1, there was also a significant difference between the groups. In an experimental rabbit uterine horn adhesion model, PRP is effective in preventing post-operative adhesion formation. CONCLUSIONS: This result may guide clinical studies using autologous PRP to prevent post-operative adhesion formation after gynecological operations.

OBJETIVO: Este estudio se llevó a cabo para investigar el efecto del plasma rico en plaquetas (PRP) autólogo sobre la adhesión intraabdominal en la línea de incisión de la cesárea en el útero. MATERIAL Y MÉTODOS: Como animales de experimentación se utilizaron 16 conejos blancos de Nueva Zelanda, de 5 meses de edad, sin aparear. Los animales se dividieron en dos grupos como grupo de control y grupo de aplicación de PRP. En cada grupo, se hizo una incisión transversal al útero para imitar la cesárea y se suturó. La relaparotomía se realizó 21 días después de la primera operación. RESULTADOS: Cuando los grupos se evaluaron en términos de inflamación, hubo una diferencia significativa entre los dos grupos. Cuando los grupos se evaluaron en términos de tinción MT y fibrosis, hubo una diferencia significativa entre los grupos. Cuando los grupos se evaluaron en términos de VEGF-1, también hubo una diferencia significativa entre los grupos. En un modelo experimental de adherencia al cuerno uterino de conejo, el PRP es eficaz para prevenir la formación de adherencias posoperatorias. CONCLUSIONES: Este resultado puede guiar los estudios clínicos que utilizan PRP autólogo para prevenir la formación de adherencias postoperatorias después de operaciones ginecológicas.

Anti-adhesive effect of naturally obtained dicalcium phosphate dihydrate nanoparticles in the rat uterine wound model.

OBJECTIVE: In this study, we aimed to compare the anti-adhesive effects of contractubex and dicalcium phosphate dihydrate (DCPD) particles in rats treated with the uterine horn adhesion model. MATERIALS AND METHODS: Newly adult, 60 Wistar albino rats were used as experimental animals. The modified rat uterine horn adhesion model was used to induce intra-abdominal adhesion. Tumor necrosis factor (TNF)-α, interleukin (IL)-1, vascular endothelial growth factor (VEGF) and transforming growth factor (TGF)-ß1 were studied for biochemical and immunohistochemical examination. RESULTS: TNF-α decreased in each group, while it decreased more in G2 and G3 than in G1. IL-1ß decreased in each group, while it decreased the most in G3. TGF-ß1 and VEGF localization was less in the G2 compared to G1, the least TGF-ß1 and VEGF immunolocalization was detected in the G3 and G4. For both antibodies, the least localization among all groups belonged to G3. From day 7 to day 21, the highest TGF-ß1 immunolocalization was observed in G1, lesser localization in G2 and lowest in G3. CONCLUSION: DCPD nanoparticles show promise as a clinical antiadhesive agent and should be further evaluated in experimental animal models and human trials.

OBJETIVO: En este estudio, nuestro objetivo fue comparar los efectos antiadhesivos de las partículas de contractubex (CTX) y fosfato dicálcico dihidratado (DCPD) en ratas tratadas con el modelo de adhesión del cuerno uterino. MATERIALES Y MÉTODOS: Como animales de experimentación se utilizaron 60 ratas Wistar albinas, recién adultas. Se usó el modelo de adhesión del cuerno uterino de rata modificado para inducir la adhesión intraabdominal. Se estudiaron TNF-α, IL-1, VEGF y TGF-ß1 para examen bioquímico e inmunohistoquímico. RESULTADOS: el TNF-α disminuyó en cada grupo, mientras que disminuyó más en G2 y G3 que en G1. IL-1ß disminuyó en cada grupo, mientras que disminuyó más en G3. La localización de TGF-ß1 y VEGF fue menor en G2 en comparación con G1, la menor inmunolocalización de TGF-ß1 y VEGF se detectó en G3 y G4. Para ambos anticuerpos, la localización mínima entre todos los grupos pertenecía a G3. Desde el día 7 hasta el día 21, la mayor inmunolocalización de TGF-ß1 se observó en G1, menor localización en G2 y menor en G3. CONCLUSIÓN: las nanopartículas de DCPD se muestran prometedoras como agentes antiadhesivos clínicos y deben evaluarse más en modelos animales experimentales y ensayos en humanos.

Histological Examination of Mitochondrial Morphology in a Parkinson's Disease Model.

Mitochondria play a central role in the energy metabolism of cells, and their function is especially important for neurons due to their high energy demand. Therefore, mitochondrial dysfunction is a pathological hallmark of various neurological disorders, including Parkinson's disease. The shape and organization of the mitochondrial network is highly plastic, which allows the cell to respond to environmental cues and needs, and the structure of mitochondria is also tightly linked to their health. Here, we present a protocol to study mitochondrial morphology in situ based on immunostaining of the mitochondrial protein VDAC1 and subsequent image analysis. This tool could be particularly useful for the study of neurodegenerative disorders because it can detect subtle differences in mitochondrial counts and shape induced by aggregates of α-synuclein, an aggregation-prone protein heavily involved in the pathology of Parkinson's disease. This method allows one to report that substantia nigra pars compacta dopaminergic neurons harboring pS129 lesions show mitochondrial fragmentation (as suggested by their reduced Aspect Ratio, AR) compared to their healthy neighboring neurons in a pre-formed fibril intracranial injection Parkinson model.

Novel Bioactive Glass/Graphene Oxide-Coated Surgical Sutures for Soft Tissue Regeneration.

The combination of a commercially available PGLA (poly[glycolide-co-l-lactide]), 90:10% suture material with bioactive bioglass nanopowders (BGNs) and graphene oxide (GO)-doped BGNs offers new opportunities for the clinical application of biomaterials in soft tissue engineering. In the present experimental work, we demonstrate that GO-doped melt-derived BGNs were synthesized via the sol-gel process. After that, novel GO-doped and undoped BGNs were used to coat resorbable PGLA surgical sutures, thereby imparting bioactivity, biocompatibility, and accelerated wound healing properties to the sutures. Stable and homogeneous coatings on the surface of the sutures were achieved using an optimized vacuum sol deposition method. The phase composition, morphology, elemental characteristics, and chemical structure of uncoated and BGNs- and BGNs/GO-coated suture samples were characterized using Fourier transform infrared spectroscopy, field emission scanning electron microscopy, associated with elemental analysis, and knot performance test. In addition, in vitro bioactivity tests, biochemical tests, and in vivo tests were performed to examine the role of BGNs and GO on the biological and histopathological properties of the coated suture samples. The results indicated that the formation of BGNs and GO was enhanced significantly on the suture surface, which allowed for enhanced fibroblast attachment, migration, and proliferation and promoted the secretion of the angiogenic growth factor to speed up wound healing. These results confirmed the biocompatibility of BGNs- and BGNs/GO-coated suture samples and the positive effect of BGNs on the behavior of L929 fibroblast cells and also showed for the first time the possibility that cells can adhere and proliferate on the BGNs/GO-coated suture samples, especially in an in vivo environment. Resorbable surgical sutures with bioactive coatings, such as those prepared herein, can be an attractive biomaterial not only for hard tissue engineering but also for clinical applications in soft tissue engineering.

The Effect on the Birth Process of Endogenous Oxytocin Release Via Coitus at Home in Pregnant Women in the Latent Phase.

OBJECTIVES: This study was conducted to determine the effect of endogenous oxytocin release via coitus at home on the delivery process in pregnant women who were not hospitalized in the latent phase. BACKGROUND: For healthy pregnant women who can deliver spontaneously, it is recommended to be admitted to the delivery room during the active phase of labor. When the pregnant woman is admitted to the delivery room in the latent phase before the active stage, pregnant women spend more time in the delivery room, which makes medical intervention inevitable. METHODS: 112 pregnant women for whom hospitalization in the latent phase was recommended were included in the randomized controlled study. They were divided into two groups in which sexual activity in the latent phase was recommended (n=56) and the control group (n=56). RESULTS: In our study, the duration of the 1st stage of labor was found to be significantly shorter in the group in which sexual activity in the latent phase was recommended, compared to the control group (p=0.001). Again, the need for amniotomy, labor induction with oxytocin, analgesics and episiotomy decreased. CONCLUSION: Sexual activity can be considered as a natural way to speed up labor, reduce medical interventions, and prevent postterm pregnancy.

Technical approaches and challenges to study AMPA receptors in oligodendrocyte lineage cells: Past, present, and future.

Receptors for α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPARs) are ligand-gated ionotropic receptors for glutamate that is a major excitatory neurotransmitter in the central nervous system. AMPARs are located at postsynaptic sites of neuronal synapses where they mediate fast synaptic signaling and synaptic plasticity. Remarkably, AMPARs are also expressed by glial cells. Their expression by the oligodendrocyte (OL) lineage cells is of special interest because AMPARs mediate fast synaptic communication between neurons and oligodendrocyte progenitor cells (OPCs), modulate proliferation and differentiation of OPCs, and may also be involved in regulation of myelination. On the other hand, during pathological conditions, AMPARs may mediate damage of the OL lineage cells. In the present review, we focus on the technical approaches that have been used to study AMPARs in the OL lineage cells, and discuss future perspectives of AMPAR research in these glial cells.

[A Case of Oropharyngeal Tularemia Mimicking Lymphoma During Pregnancy]. / Gebelikte Lenfomayi Taklit Eden Bir Orofarengeal Tularemi Olgusu.

Tularemia is a zoonotic bacterial infectious disease caused by a gram-negative coccobacillus namely Francisella tularensis. In humans, disease leads to several different clinical forms (ulceroglandular, glandular, oculoglandular, respiratory, typhoidal and oropharyngeal). Since the main mode of transmission of the disease to humans in Türkiye is by drinking water contaminated with F.tularensis, the oropharyngeal form is the most common clinical manifestation. Since tularemia cases with pregnancy are rare, the literatüre about maternal and fetal complications of tularemia is sparse. In this report, a case of oropharyngeal tularemia mimicking lymphoma during pregnancy was presented. A 33-year-old 11-week pregnant patient living in a village in Sivas province admitted to the infectious diseases and clinical microbiology outpatient clinic with the complaint of swelling in the neck region that continued for six days. The patient, who was engaged in animal husbandry stated that she consumed raw milk and admitted to the otorhinolaryngology outpatient clinic of a hospital 10 days ago with the complaints of fever, chills, and sore throat. She stated that her complaints did not regress with the amoxicillin-clavulanate treatment recommended by her doctor and she noticed the swelling in her neck on the 4th day of the treatment. Upon further questioning, it was understood that the patient had a history of consumption of unchlorinated spring water. Her vital signs were normal and physical examination revealed non-fluctuant lymph nodes with the largest of 5 x 2 cm in the right posterior cervical region, and 3 x 2 cm in the left. Laboratory tests revealed a blood leukocyte count of 13.32 x 103/mm3 (75% granulocytes), a blood hemoglobin of 11.4 g/dL, an erythrocyte sedimentation rate of 45 mm/hour, and C-reactive protein of 90 mg/L. A non-contrast MRI examination revealed wall thickening of the nasopharynx and enlarged lymph nodes which were suspicious for lymphoma with significant diffusion restriction on diffusionweighted images. As the past medical history and clinical findings were suggestive for tularemia, the microagglutination test (MAT) was studied, but it was reported as negative with a titer at 1/80. Since the patient's complaints continued and tularemia cases were encountered in our region in the past years, the repeated MAT after two weeks was reported as positive with a titer at 1/320. An oropharyngeal form of tularemia was diagnosed and oral ciprofloxacin (2 x 750 mg) was given for three weeks by starting at the 14th gestational week. Lymphoma was excluded by histopathological examination of the fine needle aspiration biopsy performed on the patient's cervical lymph nodes, but the biopsy sample was compatible with granulomatous diseases. Histopathological findings of diagnostic biopsies of the larynx and nasopharynx were reactive. A healthy male baby, 2425 grams, 47 cm, was delivered by cesarean section from the patient who presented with labor contractions at the 37th week of pregnancy. There was no sign of congenital infection in the newborn. The patient and the baby were followed up to the end of one year and no abnormality was found. The evaluation of 17 cases reported in the literatüre including this case, suggest that tularemia may progress to involve serious obstetric complications during pregnancy, such as abortion, premature birth and intrauterine fetal death when appropriate and effective antibiotic treatment is not given.

A Pharmacological Perspective on Plant-derived Bioactive Molecules for Epilepsy.

Epilepsy is a related chronic neurological condition of a predisposition for recurrent epileptic seizures, with various manifestations and causes. Although there are antiepileptic drugs, complementary natural therapies are widely used. The purpose of this systematic review was to analyze the antiepileptic/anticonvulsant pharmacological properties of plant-food derived bioactive molecules. In this regard, a systematic review of the PubMed database was made based on the inclusion criteria. Natural compounds/herbs with scientifically proven antiepileptic properties were selected. Experimental pharmacological studies in vitro and in vivo have shown that flavonoids, alkaloids and terpenoids may have anticonvulsant mechanisms similar to the new generation antiepileptic drugs. The relationships of structure-anticonvulsant effect, pharmacological models, seizure-inducing factors and response, effective dose were also analyzed and discussed. The results of in vitro and in vivo pharmacological studies analyzed in this systematic review support the clinical importance of plant-food-derived bioactive molecules for the complementary treatment of epilepsy. Thus, are opened new perspectives to develop new natural anticonvulsant drugs.

Impact of Natural Compounds on Neurodegenerative Disorders: From Preclinical to Pharmacotherapeutics.

Among the major neurodegenerative disorders (NDDs), Alzheimer's disease (AD) and Parkinson's disease (PD), are a huge socioeconomic burden. Over many centuries, people have sought a cure for NDDs from the natural herbals. Many medicinal plants and their secondary metabolites are reported with the ability to alleviate the symptoms of NDDs. The major mechanisms identified, through which phytochemicals exert their neuroprotective effects and potential maintenance of neurological health in ageing, include antioxidant, anti-inflammatory, antithrombotic, antiapoptotic, acetylcholinesterase and monoamine oxidase inhibition and neurotrophic activities. This article review the mechanisms of action of some of the major herbal products with potential in the treatment of NDDs according to their molecular targets, as well as their regional sources (Asia, America and Africa). A number of studies demonstrated the beneficial properties of plant extracts or their bioactive compounds against NDDs. Herbal products may potentially offer new treatment options for patients with NDDs, which is a cheaper and culturally suitable alternative to conventional therapies for millions of people in the world with age-related NDDs.

Multitarget Profiling of a Strigolactone Analogue for Early Events of Alzheimer's Disease: In Vitro Therapeutic Activities against Neuroinflammation.

Neuropathological changes in Alzheimer's disease (AD) are directly linked to the early inflammatory microenvironment in the brain. Therefore, disease-modifying agents targeting neuroinflammation may open up new avenues in the treatment of AD. Strigolactones (SLs), subclasses of structurally diverse and biologically active apocarotenoids, have been recently identified as novel phytohormones. In spite of the remarkable anticancer capacity shown by SLs, their effects on the brain remained unexplored. Herein, the SIM-A9 microglial cell line was used as a phenotypic screening tool to search for the representative SL, GR24, demonstrating marked potency in the suppression of lipopolysaccharide (LPS)-induced neuroinflammatory/neurotoxic mediators by regulating NF-κB, Nrf2, and PPARγ signaling. GR24 also in the brain endothelial cell line bEnd.3 mitigated the LPS-increased permeability as evidenced by reduced Evans' blue extravasation through enhancing the expression of tight junction protein, occludin. Collectively, the present work shows the anti-neuroinflammatory and glia/neuroprotective properties of GR24, making SLs promising scaffolds for the development of novel anti-AD candidates.

GR24, a synthetic analog of Strigolactones, alleviates inflammation and promotes Nrf2 cytoprotective response: In vitro and in silico evidences.

Naturally occurring phytohormones have shown distinguished potential in chemoprevention and treatment of chronic inflammatory diseases in mammalian cells. Strigolactones (SLs) are a class of carotenoid-derived lactones regulating many aspects of plant development and recently recognized as phytohormones with promising anticancer activity. In this study, GR24, a synthetic analog and representative of SLs, induced the expression of phase II detoxifying enzymes such as HO-1 and NQO1 in hepatic and macrophage cell lines under normal and inflammatory conditions, respectively. This effect has been found to be mediated by Nrf2 activation. In silico molecular docking against 16-mer peptide binding site on Keap1 suggested that GR24 may exert its biological activity by interfering with Keap1 and Nrf2 binding. GR24 also displayed remarkably potent inhibitory activity against the production of nitric oxide (NO) and molecular docking analysis on iNOS supported experimental data. Furthermore, GR24 dose dependently suppressed the LPS-induced iNOS expression at both mRNA and protein level. It also significantly decreased IL-1ß release, mRNA expression of IL-1ß and COX-2, as well as nuclear accumulation of NFÒ¡B at the low micro molar range in LPS-stimulated murine macrophages. GR24 promoted AKT activation in insulin resistant skeletal muscle cells and downregulated the expression of enzymes, PEPCK and G6Pase control the rate limiting steps of gluconeogenesis in hepatic cells. The results of molecular docking and ADMET analyses indicated that GR24 might be classified as druggable molecule in drug design. Taken together, all results suggest that SLs can be promising multi-potent botanical leads for the mitigation of inflammatory-mediated chronic disorders.