Cord Cells Research Articles

Umbilical Cord Stem Cell Stem Cell Therapy For Rare Genetic Disease Prader-Willi Syndrome

This abstract summarises the studies on the use of umbilical cord stem cells to treat Prader-Willi syn- drome. Among the various stem cells found in the umbilical cord, hematopoietic and mesenchymal stem cells may create bioactive molecules that aid in tissue repair and regeneration, control immunological responses, and give birth to a variety of cell types. Because of this, they present a feasible option for treating the multidisciplinary character of PWS. Preclinical research on PWS animal models has shown promising outcomes, with umbilical cord stem cell transplantation improving metabolic disorders, hy- hypothalamic function, and general behavior. It has been investigated if immunological regulation, trophic support, and paracrine signaling are among the factors that promote stem cell therapeutic potential. Several clinical studies employing umbilical cord stem cells to treat PWS are now underway, and the findings should aid in assessing the advantages and disadvantages of using this approach on patients. The preliminary evidence is encouraging, since some trial participants improved in hyperphagia, mus- cular tone, and cognitive ability. Although the use of umbilical cord stem cells as a PWS treatment has shown some promise, further study is required to determine its long-term safety, optimal dose, and ongoing effectiveness. A variety of key elements, such as ethical issues, regulatory frameworks, and the availability of standardized stem cell products, will have a considerable impact on the future development of this treatment technique. SD is a disease known as a neurodevelopmental problem represented through problems with social communication, sensor sensitivity, and repetitive behaviors. Despite years of study, therapy options for autism spectrum disorder (ASD) remain relatively limited. As regenerative medicine has improved, stem cell treatment has been investigated as a novel therapeutic option for the underlying neurological disorders that underpin ASD. The development, possible methods, and potential uses of stem cell treatment for autistic children are discussed in this article.

Improvement of neurogenic urinary dysfunctions in female rats treated with an injection of botulinum toxin A at the epicenter of the spinal cord injured site.

To assess the effect of an injection of botulinum toxin A (BoNT/A) at the epicenter of the spinal cord injury (SCI) site on the recovery of lower urinary tract function in female rats with thoracic SCI. Twenty-four female Wistar rats with Sham (laminectomy at T8/T9 level) or SCI (at T8/T9; 30 g compression for 5 s) were assigned into Sham-SS (injected with 5 µL of saline solution), Sham-BoNT/A (injected with 15 pg/rat, equivalent to 7.5 Units/kg of BoNT/A in 5 µL volume), SCI-SS (injured and injected with saline), SCI-BoNT/A (injured and injected with BoNT/A), N = 6 per group. Weekly evaluation of stereotyped micturition behavior, hind-limb nociception, and locomotor activity was performed 1 week before and during 6 weeks after surgery. Subsequently, all groups underwent simultaneous electromyography of the external urethral sphincter (EUS-EMG) and cystometric (CMG) studies. A compression SCI at the T8/T9 thoracic level significantly impairs sensory and locomotive functions, as well as stereotyped micturition behavior. However, these impairments were improved by BoNT/A injection after SCI. Neither injections of saline solution nor BoNT/A had an appreciable effect on the same parameters evaluated in the Sham groups. The combined EUS-EMG and CMG evaluations revealed important improvements of lower urinary tract physiology, particularly a reduction in the frequency of non-voiding contractions and the properties of EUS bursting activity indicated as the amplitude of the EUS-EMG signal and duration of burst electrical activity during effective voiding. The severe impairments on sensory and locomotive functions as well stereotyped micturition caused by an SCI could be potentially attenuated by an injection of a small amount of BoNT/A directly into the epicenter of the SCI region. A reduction in the release of neurotoxic neurotransmitters requiring the SNARE complex may be the mechanism triggered by BoNT/A to reduce neurotoxicity and hyperexcitability created in the SCI area to improve the survival of spinal cord cells involved in micturition.

Testicular Neoplasms With Sex Cord and Stromal Components Harbor a Recurrent Pattern of Chromosomal Gains

A small subset of testicular sex cord-stromal tumors, designated as Sertoli-stromal cell tumors (SSCTs), comprises a mixture of Sertoli, spindle, and/or Leydig cells. The clinicopathologic features of these tumors have not been studied in any detail, and their molecular features are unknown. We, therefore, assessed the morphologic and genomic features of 14 SSCTs, including 1 tumor with features similar to the ovarian Sertoli-Leydig cell tumor (SLCT) with retiform tubules. The median age of the patients was 24 years (range, 10-55 years), and the median tumor size was 2.3 cm (range, 0.7-4.7 cm). All tumors showed Sertoli-like sex cord cells arranged in variably developed tubular structures, typically also forming nests and cords. These imperceptibly blended with a neoplastic spindle cell stroma or, in the SLCT, vacuolated to eosinophilic Leydig cells. Genomic analysis demonstrated the presence of a hotspot loss-of-function DICER1 mutation in the SLCT (patient 1) and hotspot gain-of-function CTNNB1 mutations in the tumors of patients 2 and 3, with both CTNNB1 variants being interpreted as possible subclonal events. The mutations were the only relevant findings in the tumors of patients 1 and 2, whereas the tumor of patient 3 harbored concurrent chromosomal arm-level and chromosome-level copy number gains. Among the remaining 11 tumors, all of those that had interpretable copy number data (9 tumors) harbored multiple recurrent chromosomal arm-level and chromosome-level copy number gains suggestive of a shift in ploidy without concurrent pathogenic mutations. The results of the present study suggest that CTNNB1 mutations (likely subclonal) are only rarely present in SSCTs; instead, most of them harbor genomic alterations similar to those seen in testicular sex cord-stromal tumors with pure or predominant spindle cell components. A notable exception was a testicular SLCT with morphologic features identical to the ovarian counterpart, which harbored a DICER1 mutation.

Rspo1 and Rspo3 are required for sensory lineage neural crest formation in mouse embryos.

R-spondins (Rspos) are secreted proteins that modulate Wnt/β-catenin signaling. At the early stages of spinal cord development, Wnts (Wnt1, Wnt3a) and Rspos (Rspo1, Rspo3) are co-expressed in the roof plate, suggesting that Rspos are involved in development of dorsal spinal cord and neural crest cells in cooperation with Wnt ligands. Here, we found that Rspo1 and Rspo3, as well as Wnt1 and Wnt3a, maintained roof-plate-specific expression until late embryonic stages. Rspo1- and Rspo3-double-knock-out (dKO) embryos partially exhibited the phenotype of Wnt1 and Wnt3a dKO embryos. While the number of Ngn2-positive sensory lineage neural crest cells is reduced in Rspo-dKO embryos, development of dorsal spinal cord, including its size and dorso-ventral patterning in early development, elongation of the roof plate, and proliferation of ependymal cells, proceeded normally. Consistent with these slight defects, Wnt/β-catenin signaling was not obviously changed in developing spinal cord of dKO embryos. Our results show that Rspo1 and Rspo3 are dispensable for most developmental processes involving roof plate-derived Wnt ligands, except for specification of a subtype of neural crest cells. Thus, Rspos may modulate Wnt/β-catenin signaling in a context-dependent manner.

The Impact of Biomaterial Surface Properties on Engineering Neural Tissue for Spinal Cord Regeneration.

Tissue engineering for spinal cord injury (SCI) remains a complex and challenging task. Biomaterial scaffolds have been suggested as a potential solution for supporting cell survival and differentiation at the injury site. However, different biomaterials display multiple properties that significantly impact neural tissue at a cellular level. Here, we evaluated the behavior of different cell lines seeded on chitosan (CHI), poly (ε-caprolactone) (PCL), and poly (L-lactic acid) (PLLA) scaffolds. We demonstrated that the surface properties of a material play a crucial role in cell morphology and differentiation. While the direct contact of a polymer with the cells did not cause cytotoxicity or inhibit the spread of neural progenitor cells derived from neurospheres (NPCdn), neonatal rat spinal cord cells (SCC) and NPCdn only attached and matured on PCL and PLLA surfaces. Scanning electron microscopy and computational analysis suggested that cells attached to the material's surface emerged into distinct morphological populations. Flow cytometry revealed a higher differentiation of neural progenitor cells derived from human induced pluripotent stem cells (hiPSC-NPC) into glial cells on all biomaterials. Immunofluorescence assays demonstrated that PCL and PLLA guided neuronal differentiation and network development in SCC. Our data emphasize the importance of selecting appropriate biomaterials for tissue engineering in SCI treatment.

Electroacupuncture alleviates neuropathic pain caused by SNL by promoting M2 microglia polarization through PD-L1

As a common clinical disease, neuropathic pain is difficult to be cured with drugs. The occurrence and progression of pain is closely related to the response of spinal microglia. Aspartof the regulation of microglialactivity,PD-L1 playsacriticalrole. Loss of PD-L1 promoted the polarization of M1-like microglia. Increased expression of PD-L1 promoted M2-like polarization. Electroacupuncture has a significant analgesic effect in clinical practice, but its specific mechanism remains to be further explored. In this study, we verified the role of PD-L1 in EA analgesia and the underlying molecular mechanism through spinal nerve ligation (SNL) in rats and lipopolysaccharide (LPS)-treated BV2 microglial cells. Forbehavioralstudiesofrats,mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) were measured, and spinal cord neuros were examined under transmission electron microscopyto determine changes to their myelin structure. The expression levels of PD-L1 and M1/M2-specific markers in rat spinal cord and BV2 microglial cells were measured by enzyme-linked immunosorbent assay, flow cytometry, immunofluorescence staining and Western blot analysis. Our study showed that EA increased the pain threshold, reduced the destruction of myelin structure, promoted the expression of PD-L1 and PD-1, inhibited the MAPK signaling pathway, and promoted the conversion of microglial polarization from the M1 phenotype to the M2 phenotype in SNL rats. PD-L1 knockdown reversed these effects of EA. In addition, PD-L1 knockdown activated the MAPK signaling pathway, promoted microglial polarization to the M1 phenotype, decreased the expression of anti-inflammatory mediators and increased the expression of proinflammatory factors in LPS-stimulated BV2 microglial cells. Our results showed that EA may regulate the excitability of primary afferent neurons through PD-L1 and then inhibit the MAPK signaling pathway to promote the transformation of activated M1 microglia into M2 microglia, reduce inflammatory reactions, and finally achieve analgesic effects. A therapy targeting PD-L1 may be an effective strategy for treating neuropathic pain.

Edge-Functionalized Graphene/Polydimethylsiloxane Composite Films for Flexible Neural Cuff Electrodes.

The design of neural electrodes has changed in the past decade, driven mainly by the development of new materials that open the possibility of manufacturing electrodes with adaptable mechanical properties and promising electrical properties. In this paper, we report on the mechanical and electrochemical properties of a polydimethylsiloxane (PDMS) composite with edge-functionalized graphene (EFG) and demonstrate its potential for use in neural implants with the fabrication of a novel neural cuff electrode. We have shown that a 200 μm thick 1:1 EFG/PDMS composite film has a stretchability of up to 20%, a Young's modulus of 2.52 MPa, and a lifetime of more than 10000 mechanical cycles, making it highly suitable for interfacing with soft tissue. Electrochemical characterization of the EFG/PDMS composite film showed that the capacitance of the composite increased up to 35 times after electrochemical reduction, widening the electrochemical water window and remaining stable after soaking for 5 weeks in phosphate buffered saline. The electrochemically activated EFG/PDMS electrode had a 3 times increase in the charge injection capacity, which is more than double that of a commercial platinum-based neural cuff. Electrochemical and spectrochemical investigations supported the conclusion that this effect originated from the stable chemisorption of hydrogen on the graphene surface. The biocompatibility of the composite was confirmed with an in vitro cell culture study using mouse spinal cord cells. Finally, the potential of the EFG/PDMS composite was demonstrated with the fabrication of a novel neural cuff electrode, whose double-layered and open structured design increased the cuff stretchability up to 140%, well beyond that required for an operational neural cuff. In addition, the cuff design offers better integration with neural tissue and simpler nerve fiber installation and locking.

Stem cell sources from human biological waste material: a role for the umbilical cord and dental pulp stem cells for regenerative medicine.

Stem cell research with biological waste material is an area that holds promise to revolutionize treatment modalities and clinical practice. The interest in surgical remnants is increasing with time as research on human embryonic stem cells remains controversial due to legal and ethical issues. Perhaps, these restrictions are the motivation for the use of alternative mesenchymal stem cell (MSC) sources in the regenerative field. Stem cells (SCs) of Umbilical Cord (UC) and Dental Pulp (DP) have almost similar biological characteristics to other MSCs and can differentiate into a number of cell lineages with enormous potential future prospects. A concise critical observation of UC-MSCs and DP-MSCs is presented here reviewing articles from the last two decades along with other stem cell sources from different biological waste materials.

Activation of Inflammasome during Bluetongue Virus Infection.

Bluetongue virus (BTV), a double-stranded RNA virus belonging to the Sedoreoviridae family, provokes an economically important disease in ruminants. In this study, we show that the production of activated caspase-1 and interleukin 1 beta (IL-1β) is induced in BTV-infected cells. This response seems to require virus replication since a UV-inactivated virus is unable to activate this pathway. In NLRP3-/- cells, BTV could not trigger further IL-1β synthesis, indicating that it occurs through NLRP3 inflammasome activation. Interestingly, we observed differential activation levels in bovine endothelial cells depending on the tissue origin. In particular, inflammasome activation was stronger in umbilical cord cells, suggesting that these cells are more prone to induce the inflammasome upon BTV infection. Finally, the strength of the inflammasome activation also depends on the BTV strain, which points to the importance of viral origin in inflammasome modulation. This work reports the crucial role of BTV in the activation of the NLRP3 inflammasome and further shows that this activation relies on BTV replication, strains, and cell types, thus providing new insights into BTV pathogenesis.

Prospects of pharmacological regulation of aquaporin function in CNS diseases

The review analyzes the results of scientific research on the role of aquaporins in the pathogenesis of CNS diseases and the possibility of their pharmacological regulation.
 Aquaporins (AQP) are proteins involved in the transmembrane transport of water and other substances. They form the water channels of cell membranes and are widely represented in various mammalian cells, including the membranes of human brain and spinal cord cells. To date, about 300 types of proteins of the aquaporin family have been discovered, of which 13 (AQP0AQP12) have been identified in human cells. Localization of different types of AQP in CNS structures, their functional activity and involvement in the development of CNS diseases differ. There are mainly three types of AQPs in the central nervous system: AQP1, AQP4 and AQP9. The results of scientific research indicate the most important role of AQP in maintaining water-salt homeostasis and ensuring physiological processes in the central nervous system, and also confirm the role of AQP in the pathogenesis of a number of diseases of the central nervous system (cerebral edema of various genesis, invasion of tumor cells and the formation of peritumorous edema, in the development of autoimmune diseases opticomyelitis, Alzheimers disease). Pharmacological regulation of the functional activity of aquaporins can influence the course of these diseases. Therefore, there is a natural interest in drugs that can change the expression of AQP.
 Proteins of the aquaporin family provide transmembrane transport of water and play an essential role in the development of pathological conditions of the central nervous system. They can be potential targets for pharmacological effects in a number of diseases of the central nervous system. The search and study of drugs affecting the expression and functional activity of AQP is pathogenetically justified and is a promising direction in the development of pharmacotherapy strategies for cerebral edema, malignant brain tumors and other CNS diseases.

Age-dependent immune and lymphatic responses after spinal cord injury

Spinal cord injury (SCI) causes lifelong debilitating conditions. Previous works demonstrated the essential role of the immune system in recovery after SCI. Here, we explored the temporal changes of the response after SCI in young and aged mice in order to characterize multiple immune populations within the mammalian spinal cord. We revealed substantial infiltration of myeloid cells to the spinal cord in young animals, accompanied by changes in the activation state of microglia. In contrast, both processes were blunted in aged mice. Interestingly, we discovered the formation of meningeal lymphatic structures above the lesion site, and their role has not been examined after contusive injury. Our transcriptomic data predicted lymphangiogenic signaling between myeloid cells in the spinal cord and lymphatic endothelial cells (LECs) in the meninges after SCI. Together, our findings delineate how aging affects the immune response following SCI and highlight the participation of the spinal cord meninges in supporting vascular repair.

The Use of Stem Cell Therapy in the Treatment of Autism Spectrum Disorder

Research on the use of stem cell therapy in regenerative medicine has shown great potential in the treatment of neurological disorders. Specifically, mesenchymal stem cells, adult stem cells from the umbilical cord and embryonic stem cells have been used in both animal models and clinical trials to treat autism spectrum disorder. Autism Spectrum Disorder (ASD) is an incurable neurological disorder characterized by behavioral and neuroanatomical abnormalities, commonly co-occurring with other neurological disorders including anxiety, depression and obsessive-compulsive disorder. Stem cell therapies are currently being researched to alleviate the behavioral tendencies typically seen in individuals with ASD.

Abstract 3620: N-myristoylation inhibition reduces angiogenesis and cancer cell migration

Abstract Myristoylation is the modification of proteins by the 14-carbon fatty acid myristate. In humans, two N-myristoyltransferases (NMT1 and NMT2) catalyze myristate transfer onto >200 proteins to regulate membrane binding and signal transduction. The pan-NMT inhibitor PCLX-001 has been in phase I clinical trials over a year for the treatment of lymphoma and advanced solid malignancies. Lack of myristoylation promotes the degradation of numerous normally myristoylated proteins like the proto-oncogenic Src family kinases (SFKs). SFKs like Src and Lyn are essential for downstream signaling of Vascular Endothelial Growth Factor (VEGF) and Epidermal Growth Factor (EGF) receptor tyrosine kinases. Thus, SFKs are critical for angiogenesis and cell motility. Angiogenesis is essential for tumor growth and dissemination of cancer cells to distal locations. VEGF-induced angiogenesis requires Src activation, suggesting that PCLX-001 may have antiangiogenic properties. SFKs also promote cell migration/metastasis, the leading cause of cancer-associated mortality. Lyn SFK knockdown was shown to reduce breast cancer migration and neighbouring tissue invasion, suggesting that PCLX-001 may also inhibit cell migration/metastasis. We investigated the antiangiogenic properties of PCLX-001 in vitro using HUVEC umbilical cord cells. PCLX-001 treatment significantly reduced HUVEC sprouting and tube-formation to levels lower than two FDA-approved angiogenesis inhibitors Sorafenib and Sunitinib. PCLX-001 also significantly reduced neo-vascularisation in vivo at lower concentrations than these two drugs using a chicken chorioallantoic membrane model, demonstrating the high potential of myristoylation inhibitors to reduce angiogenesis. We then validated our observations in vivo using a HT-1376 bladder mouse xenograft model. Tumors from mice treated for 28 days at increasing PCLX-001 concentrations showed significant reduction of Src, Lyn, and VEGF receptor protein levels as measured by immunohistochemistry, further validating PCLX-001 effect in vivo. We hypothesize that PCLX-001 acts downstream of VEGF/EGF receptors by inducing degradation of un-myristoylated SFKs. We confirmed this by knocking down NMT1 or treating breast cancer cells with PCLX-001 and found that both significantly reduced SFK protein levels. In a wound-healing assay using PCLX-001, we observed significant dose-dependent cell migration inhibition. PCLX-001 also dose-dependently reduced migration and invasion in transwell migration/invasion assays, indicating that myristoylation is required for optimal migration and potentially cancer cell metastasis. Overall, by lowering SFK levels, PCLX-001 reduces angiogenesis, cell migration/invasion, and thus potentially cancer metastasis. Reducing these classical cancer hallmarks in malignant cells may benefit a wide array of cancer patients and ultimately improve cancer treatment outcomes. Citation Format: Rony Pain, Erwan Beauchamp, Katia Carmine-Simmen, Jay Gamma, Rebecca Reif, Abul Azad, Allan Murray, John Lewis, Luc Berthiaume. N-myristoylation inhibition reduces angiogenesis and cancer cell migration. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3620.

Short-chain fatty acids ameliorate spinal cord injury recovery by regulating the balance of regulatory T cells and effector IL-17+ γδ T cells.

Spinal cord injury (SCI) causes motor, sensory, and autonomic dysfunctions. The gut microbiome has an important role in SCI, while short-chain fatty acids (SCFAs) are one of the main bioactive mediators of microbiota. In the present study, we explored the effects of oral administration of exogenous SCFAs on the recovery of locomotor function and tissue repair in SCI. Allen's method was utilized to establish an SCI model in Sprague-Dawley (SD) rats. The animals received water containing a mixture of 150 mmol/L SCFAs after SCI. After 21 d of treatment, the Basso, Beattie, and Bresnahan (BBB) score increased, the regularity index improved, and the base of support (BOS) value declined. Spinal cord tissue inflammatory infiltration was alleviated, the spinal cord necrosis cavity was reduced, and the numbers of motor neurons and Nissl bodies were elevated. Enzyme-linked immunosorbent assay (ELISA), real-time quantitative polymerase chain reaction (qPCR), and immunohistochemistry assay revealed that the expression of interleukin (IL)‍-10 increased and that of IL-17 decreased in the spinal cord. SCFAs promoted gut homeostasis, induced intestinal T cells to shift toward an anti-inflammatory phenotype, and promoted regulatory T (Treg) cells to secrete IL-10, affecting Treg cells and IL-17+ γδ T cells in the spinal cord. Furthermore, we observed that Treg cells migrated from the gut to the spinal cord region after SCI. The above findings confirm that SCFAs can regulate Treg cells in the gut and affect the balance of Treg and IL-17+ γδ T cells in the spinal cord, which inhibits the inflammatory response and promotes the motor function in SCI rats. Our findings suggest that there is a relationship among gut, spinal cord, and immune cells, and the "gut-spinal cord-immune" axis may be one of the mechanisms regulating neural repair after SCI.

Preparation of Primary Mixed Glial Cell Cultures from Adult Mouse Spinal Cord Tissue.

Central nervous system glial cells are known to mediate many neurocognitive/neurodegenerative diseases, including Alzheimer's and Parkinson's diseases. Similar glial responses have been recognized as critical factors contributing to the development of diseases in the peripheral nervous system, including various types of peripheral neuropathies, such as peripheral nerve injury-induced neuropathic pain, diabetic neuropathy, and HIV-associated sensory neuropathy. Investigation of the central mechanisms of these peripherally-manifested diseases often requires the examination of spinal cord glial cells at cellular/molecular levels in vitro. When using rodent models to study these diseases, many investigators have chosen to use neonatal cerebral cortices to prepare glial cultures or immortalized cell lines in order to obtain sufficient numbers of cells for assessment. However, differences in responses between cell lines versus primary cultures, neonatal vs. adult cells, and brain vs. spinal cord cells may result in misleading data. Here, we describe a protocol for preparing mixed glial cells from adult mouse spinal cord that can be used for direct in vitro evaluations or further preparation of microglia-enriched and microglia-depleted cells. In this protocol, spinal cord tissue is enzymatically dissociated and adult mixed glial cells are ready to be used between 12 and 14 days after the establishment of the culture. This protocol may be further refined to prepare spinal cord glial cells from spinal cord tissues of adult rats and potentially other species. Mixed glial cultures can be prepared from animals of different strains or post-in vivo manipulations and therefore are suitable for studying a variety of diseases/disorders that involve spinal cord pathological changes, such as amyotrophic lateral sclerosis and multiple sclerosis, as well as toxin-induced changes. © 2023 Wiley Periodicals LLC. Basic Protocol: Preparation of primary mixed glial cell cultures from adult mouse spinal cord tissue.

Prospects of pharmacological regulation of aquaporin function in CNS diseases

The review analyzes the results of scientific research on the role of aquaporins in the pathogenesis of CNS diseases and the possibility of their pharmacological regulation.
 Aquaporins (AQP) are proteins involved in the transmembrane transport of water and other substances. They form the water channels of cell membranes and are widely represented in various mammalian cells, including the membranes of human brain and spinal cord cells. To date, about 300 types of proteins of the aquaporin family have been discovered, of which 13 (AQP0AQP12) have been identified in human cells. Localization of different types of AQP in CNS structures, their functional activity and involvement in the development of CNS diseases differ. There are mainly three types of AQPs in the central nervous system: AQP1, AQP4 and AQP9. The results of scientific research indicate the most important role of AQP in maintaining water-salt homeostasis and ensuring physiological processes in the central nervous system, and also confirm the role of AQP in the pathogenesis of a number of diseases of the central nervous system (cerebral edema of various genesis, invasion of tumor cells and the formation of peritumorous edema, in the development of autoimmune diseases opticomyelitis, Alzheimers disease). Pharmacological regulation of the functional activity of aquaporins can influence the course of these diseases. Therefore, there is a natural interest in drugs that can change the expression of AQP.
 Proteins of the aquaporin family provide transmembrane transport of water and play an essential role in the development of pathological conditions of the central nervous system. They can be potential targets for pharmacological effects in a number of diseases of the central nervous system. The search and study of drugs affecting the expression and functional activity of AQP is pathogenetically justified and is a promising direction in the development of pharmacotherapy strategies for cerebral edema, malignant brain tumors and other CNS diseases.

Laparoscopic assisted removal of large ovarian mass causing precocious puberty in an infant—a case report

BackgroundSex cord and stromal tumors are a heterogeneous group of tumors that arise from gonadal sex cord cells, gonadal stromal cells, or both. They are divided into pure stromal tumors, pure sex cord tumors, and mixed tumors. Some of these tumors are hormonally active, producing androgens and estrogens, and may therefore exhibit virilization or excess estrogen. Sertoli-Leydig cell tumors are rare tumors belonging to mixed tumors representing less than 0.5% of ovarian tumors. Few cases have been reported in the medical literature.Case presentationWe report the case of a 1-year-old girl who was admitted for breast lumps and pubic hair with intermittent painless vaginal bleeding in the past 2 weeks. The abdominal examination objectified the presence of an intraperitoneal mass to which an abdominal ultrasound and computerized tomography (CT) scan had confirmed the presence of a right ovarian mass. A laparoscopy was performed which showed an encapsulated mass arriving from the right ovary replacing the normal ovarian tissue. Laparoscopic-assisted removal of the entire mass was done. The postoperative course was uneventful. The histopathological study demonstrated an intermediately differentiated Sertoli cell tumor with an intact capsule, no lymphovascular invasion, or heterologous elements (TNM stage 1).ConclusionsAlthough Sertoli-Leydig tumors are commonly seen after the second decade of life in young women, their discovery before puberty is not uncommon. Mass syndrome and signs of virilization are two frequently reported signs that should prompt the clinician to mention this entity among the differential diagnoses. The first-line radiological examination is pelvic ultrasound. The treatment is mainly based on surgery. The prognosis is excellent especially if the tumor is well differentiated.

An ependymal cell census identifies heterogeneous and ongoing cell maturation in the adult mouse spinal cord that changes dynamically on injury.

The adult spinal cord stem cell potential resides within the ependymal cell population and declines with age. Ependymal cells are, however, heterogeneous, and the biological diversity this represents and how it changes with age remain unknown. Here, we present a single-cell transcriptomic census of spinal cord ependymal cells from adult and aged mice, identifying not only all known ependymal cell subtypes but also immature as well as mature cell states. By comparing transcriptomes of spinal cord and brain ependymal cells, which lack stem cell abilities, we identify immature cells as potential spinal cord stem cells. Following spinal cord injury, these cells re-enter the cell cycle, which is accompanied by a short-lived reversal of ependymal cell maturation. We further analyze ependymal cells in the human spinal cord and identify widespread cell maturation and altered cell identities. This in-depth characterization of spinal cord ependymal cells provides insight into their biology and informs strategies for spinal cord repair.

Ulinastatin inhibits microglia activation in spinal cord via P2Y12 receptor in a rat neuropathic pain model

ABSTRACT Ulinastatin, a broad spectrum of serine protease inhibitor, has been found to alleviate neuropathic pain (NPP). However, its mechanism is not completely clear. Here, a sciatic nerve ligation rat model and BV2 microglial cells were used to investigate the effect of Ulinastatin on the activation of microglia and P2Y12 receptors in vivo and in vitro. Levels of P2Y12 receptor and NF-κB (P65) expression in the dorsal horn of the lumbar enlargement region of the spinal cord and BV2 cells were assessed by immunohistochemistry and double-label immunofluorescence assays. Levels of IL-1β and TNF-α in cell culture medium and cerebrospinal fluid (CSF) were examined by ELISA. The results showed that Ulinastatin reduced the release of inflammatory IL-1β and TNF-α by inhibiting the activation of spinal microglia. Ulinastatin down-regulated P2Y12 receptor and NF-κB (P65) expression in the spinal microglia of the chronic constrictive injury model. The results indicated that Ulinastatin may attenuate the activation of spinal microglia after peripheral nerve injury by inhibiting the activation of P2Y12 receptor signal pathway in microglia. NF-kB may play a key role in the mechanism of Ulinastatin.

Novel neuron-Schwann cell co-culture models to study peripheral nerve degeneration and regeneration.

Novel neuron-Schwann cell co-culture models to study peripheral nerve degeneration and regeneration.