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Zhong Nan Da Xue Xue Bao. Yi Xue Ban =... Oct 2023The complement system is an important part of the innate immune system, including more than 50 secretory proteins and membrane-bound proteins, and it contributes to the...
The complement system is an important part of the innate immune system, including more than 50 secretory proteins and membrane-bound proteins, and it contributes to the clearance of apoptotic cells and invading pathogens to limit inflammatory immune responses and maintaining brain homeostasis. Complement activity is strictly regulated to protect cells from random attacks or to prevent the deposition of complement proteins in physiological cases. However, overactivation or abnormal regulation of the complement cascade in the brain can lead to neuronal damage and brain dysfunction. Recent studies have pointed out that changes in complement molecules exist in patients with psychiatric diseases and play an important role in the occurrence and development of diseases by regulating the function of neurons and glial cells. Therefore, summarizing the latest research progress of complement system in psychiatric diseases such as schizophrenia, autism spectrum disorder, major depression, bipolar disorder and anxiety disorder can provide new ideas for preventing and controlling psychiatric diseases caused by abnormal activation of complement system.
Topics: Humans; Autism Spectrum Disorder; Mental Disorders; Complement System Proteins; Anxiety Disorders; Depressive Disorder, Major; Membrane Proteins
PubMed: 38432883
DOI: 10.11817/j.issn.1672-7347.2023.230109 -
Stem Cell Research & Therapy Sep 2023Refractory epilepsy is also known as drug-resistant epilepsy with limited clinical treatment. Benefitting from its safety and easy availability, olfactory mucosa...
BACKGROUND AND AIMS
Refractory epilepsy is also known as drug-resistant epilepsy with limited clinical treatment. Benefitting from its safety and easy availability, olfactory mucosa mesenchymal stem cells (OM-MSCs) are considered a preferable MSC source for clinical application. This study aims to investigate whether OM-MSCs are a promising alternative source for treating refractory epilepsy clinically and uncover the mechanism by OM-MSCs administration on an epileptic mouse model.
METHODS
OM-MSCs were isolated from turbinal and characterized by flow cytometry. Autologous human OM-MSCs treatment on a patient was carried out using intrathecal administration. Epileptic mouse model was established by 1 mg/kg scopolamine and 300 mg/kg pilocarpine treatment (intraperitoneal). Stereotaxic microinjection was employed to deliver the mouse OM-MSCs. Mouse electroencephalograph recording was used to investigate the seizures. Brain structure was evaluated by magnetic resonance imaging (MRI). Immunohistochemical and immunofluorescent staining of GFAP, IBA1, MAP2, TUBB3, OLIG2, CD4, CD25, and FOXP3 was carried out to investigate the neural cells and Treg cells. QRT-PCR and ELISA were performed to determine the cytokines (Il1b, Il6, Tnf, Il10) on mRNA and protein level. Y-maze, the object location test, and novel object recognition test were performed to measure the cognitive function. Footprint test, rotarod test, balance beam test, and grip strength test were conducted to evaluate the locomotive function. Von Frey testing was carried out to assess the mechanical allodynia.
RESULTS
Many beneficial effects of the OM-MSC treatment on disease status, including seizure type, frequency, severity, duration, and cognitive function, and no apparent adverse effects were observed at the 8-year follow-up case. Brain MRI indicated that autologous OM-MSC treatment alleviated brain atrophy in epilepsy patients. A study in an epileptic mouse model revealed that OM-MSC treatment recruited Treg cells to the brain, inhibited inflammation, rebuilt the neural network, and improved the cognitive, locomotive, and perceptive functions of epileptic mice.
CONCLUSIONS
Autologous OM-MSC treatment is efficacious for improving chronic refractory epilepsy, suggesting a future therapeutic candidate for epilepsy.
TRIAL REGISTRATION
The study was registered with Chinese Clinical Trial Registry (ChiCTR2200055357).
Topics: Humans; Animals; Mice; Drug Resistant Epilepsy; Brain; Neural Networks, Computer; Disease Models, Animal; Mesenchymal Stem Cells; Olfactory Mucosa
PubMed: 37674249
DOI: 10.1186/s13287-023-03458-6 -
Seminars in Cell & Developmental Biology Mar 2024Membrane structural integrity is essential for optimal mitochondrial function. These organelles produce the energy needed for all vital processes, provided their outer... (Review)
Review
Membrane structural integrity is essential for optimal mitochondrial function. These organelles produce the energy needed for all vital processes, provided their outer and inner membranes are intact. This prevents the release of mitochondrial apoptogenic factors into the cytosol and ensures intact mitochondrial membrane potential (ΔΨ) to sustain ATP production. Cell death by apoptosis is generally triggered by outer mitochondrial membrane permeabilization (MOMP), tightly coupled with loss of ΔΨ . As these two processes are essential for both mitochondrial function and cell death, researchers have devised various techniques to assess them. Here, we discuss current methods and biosensors available for detecting MOMP and measuring ΔΨ , focusing on their advantages and limitations and discuss what new imaging tools are needed to improve our knowledge of mitochondrial function.
Topics: Mitochondrial Membranes; Membrane Potentials; Mitochondria; Apoptosis; Biosensing Techniques
PubMed: 37438211
DOI: 10.1016/j.semcdb.2023.07.003 -
Clinical Implant Dentistry and Related... Aug 2023Analysis of the 3-dimensional implant position, the bone defect morphology, and the soft tissue situation guides the decision to preserve or to remove an implant with a... (Review)
Review
INTRODUCTION
Analysis of the 3-dimensional implant position, the bone defect morphology, and the soft tissue situation guides the decision to preserve or to remove an implant with a severe peri-implantitis lesion. The aim of this narrative review was to analyze and to comprehensively illustrate the treatment options focusing on peri-implant bone regeneration in presence of severe peri-implant bone loss.
METHODS
A database search was performed independently by the two reviewers to identify case reports, case series, cohort, retrospective, and prospective studies about peri-implant bone regeneration with a follow-up of at least 6 months. Of the 344 studies issued during the database analysis, 96 publications were selected by the authors for this review.
RESULTS
Deproteinized bovine bone mineral remains the best documented material for defect regeneration in peri-implantitis in combination with or without a barrier membrane. While studies using autogenous bone in peri-implantitis therapy are rarely found, they do report favorable potential of vertical bone regeneration. Moreover, while membranes are an inherent part of the guided bone regeneration, a 5-year follow-up study demonstrated clinical and radiographic improvements with and without a membrane. The administration of systemic antibiotics is frequently performed in clinical studies observing regenerative surgical peri-implantitis therapy, but the analysis of the literature does not support a positive effect of this medication. Most studies for regenerative peri-implantitis surgery recommend the removal of the prosthetic rehabilitation and the use a marginal incision with a full-thickness access flap elevation. This allows for a good overview for regenerative procedures with a certain risk of wound dehiscences and incomplete regeneration. An alternative approach referring to the poncho technique may reduce the risk of dehiscence. The effectiveness of implant surface decontamination might have an impact on peri-implant bone regeneration without any clinical superiority of a certain technique.
CONCLUSION
The available literature reveals that the success of peri-implantitis therapy is limited to the reduction of bleeding on probing, the improvement of the peri-implant probing depth and a small amount of vertical defect fill. On this basis, no specific recommendations for bone regeneration in surgical peri-implantitis therapy can be made. Innovative approaches for flap design, surface decontamination, bone defect grafting material, and soft tissue augmentation should be followed closely to find advanced techniques for favorable peri-implant bone augmentation.
Topics: Humans; Animals; Cattle; Peri-Implantitis; Dental Implants; Follow-Up Studies; Prospective Studies; Retrospective Studies; Bone Regeneration
PubMed: 37199027
DOI: 10.1111/cid.13209 -
Terminal differentiation of villus tip enterocytes is governed by distinct Tgfβ superfamily members.EMBO Reports Sep 2023The protective and absorptive functions of the intestinal epithelium rely on differentiated enterocytes in the villi. The differentiation of enterocytes is orchestrated...
The protective and absorptive functions of the intestinal epithelium rely on differentiated enterocytes in the villi. The differentiation of enterocytes is orchestrated by sub-epithelial mesenchymal cells producing distinct ligands along the villus axis, in particular Bmps and Tgfβ. Here, we show that individual Bmp ligands and Tgfβ drive distinct enterocytic programs specific to villus zonation. Bmp4 is expressed from the centre to the upper part of the villus and activates preferentially genes connected to lipid uptake and metabolism. In contrast, Bmp2 is produced by villus tip mesenchymal cells and it influences the adhesive properties of villus tip epithelial cells and the expression of immunomodulators. Additionally, Tgfβ induces epithelial gene expression programs similar to those triggered by Bmp2. Bmp2-driven villus tip program is activated by a canonical Bmp receptor type I/Smad-dependent mechanism. Finally, we establish an organoid cultivation system that enriches villus tip enterocytes and thereby better mimics the cellular composition of the intestinal epithelium. Our data suggest that not only a Bmp gradient but also the activity of individual Bmp drives specific enterocytic programs.
Topics: Enterocytes; Ligands; Intestinal Mucosa; Transforming Growth Factor beta; Bone Morphogenetic Proteins; Cell Differentiation
PubMed: 37493498
DOI: 10.15252/embr.202256454 -
The Journal of Biological Chemistry Sep 2023Long-range membrane traffic is guided by microtubule-associated proteins and posttranslational modifications, which collectively comprise a traffic code. The regulatory...
Long-range membrane traffic is guided by microtubule-associated proteins and posttranslational modifications, which collectively comprise a traffic code. The regulatory principles of this code and how it orchestrates the motility of kinesin and dynein motors are largely unknown. Septins are a large family of GTP-binding proteins, which assemble into complexes that associate with microtubules. Using single-molecule in vitro motility assays, we tested how the microtubule-associated SEPT2/6/7, SEPT2/6/7/9, and SEPT5/7/11 complexes affect the motilities of the constitutively active kinesins KIF5C and KIF1A and the dynein-dynactin-bicaudal D (DDB) motor complex. We found that microtubule-associated SEPT2/6/7 is a potent inhibitor of DDB and KIF5C, preventing mainly their association with microtubules. SEPT2/6/7 also inhibits KIF1A by obstructing stepping along microtubules. On SEPT2/6/7/9-coated microtubules, KIF1A inhibition is dampened by SEPT9, which alone enhances KIF1A, showing that individual septin subunits determine the regulatory properties of septin complexes. Strikingly, SEPT5/7/11 differs from SEPT2/6/7, in permitting the motility of KIF1A and immobilizing DDB to the microtubule lattice. In hippocampal neurons, filamentous SEPT5 colocalizes with somatodendritic microtubules that underlie Golgi membranes and lack SEPT6. Depletion of SEPT5 disrupts Golgi morphology and polarization of Golgi ribbons into the shaft of somato-proximal dendrites, which is consistent with the tethering of DDB to microtubules by SEPT5/7/11. Collectively, these results suggest that microtubule-associated complexes have differential specificities in the regulation of the motility and positioning of microtubule motors. We posit that septins are an integral part of the microtubule-based code that spatially controls membrane traffic.
Topics: Dyneins; Kinesins; Microtubule-Associated Proteins; Septins; COS Cells; HEK293 Cells; Humans; Animals; Chlorocebus aethiops; Protein Transport
PubMed: 37495111
DOI: 10.1016/j.jbc.2023.105084 -
Journal of the American Chemical Society Jul 2023Cholesterol promotes the structural integrity of the fluid cell membrane and interacts dynamically with many membrane proteins to regulate function. Understanding...
Cholesterol promotes the structural integrity of the fluid cell membrane and interacts dynamically with many membrane proteins to regulate function. Understanding site-resolved cholesterol structural dynamics is thus important. This long-standing challenge has thus far been addressed, in part, by selective isotopic labeling approaches. Here we present a new 3D solid-state NMR (SSNMR) experiment utilizing scalar C-C polarization transfer and recoupling of the H-C interactions in order to determine average dipolar couplings for all H-C vectors in uniformly C-enriched cholesterol. The experimentally determined order parameters (OP) agree exceptionally well with molecular dynamics (MD) trajectories and reveal coupling among several conformational degrees of freedom in cholesterol molecules. Quantum chemistry shielding calculations further support this conclusion and specifically demonstrate that ring tilt and rotation are coupled to changes in tail conformation and that these coupled segmental dynamics dictate the orientation of cholesterol. These findings advance our understanding of physiologically relevant dynamics of cholesterol, and the methods that revealed them have broader potential to characterize how structural dynamics of other small molecules impact their biological functions.
Topics: Magnetic Resonance Spectroscopy; Cell Membrane; Magnetic Resonance Imaging; Molecular Conformation; Cholesterol
PubMed: 37410392
DOI: 10.1021/jacs.3c01775 -
Cell Surface (Amsterdam, Netherlands) Dec 2023Across all kingdoms of life, cells secrete an extracellular polymer mesh that in turn feeds back onto them. This entails physical connections between the plasma membrane... (Review)
Review
Across all kingdoms of life, cells secrete an extracellular polymer mesh that in turn feeds back onto them. This entails physical connections between the plasma membrane and the polymer mesh. In plant cells, one connection stands out: the Hechtian strand which, during plasmolysis, reflects the existence of a physical link between the plasma membrane of the retracting protoplast and the cell wall. The Hechtian strand is part of a larger structure, which we call the Hechtian structure, that comprises the Hechtian strand, the Hechtian reticulum and the Hechtian attachment sites. Although it has been observed for more than 100 years, its molecular composition and biological functions remain ill-described. A comprehensive characterization of the Hechtian structure is a critical step towards understanding this plasma membrane-cell wall connection and its relevance in cell signaling. This short review intends to highlight the main features of the Hechtian structure, in order to provide a clear framework for future research in this under-explored and promising field.
PubMed: 38024561
DOI: 10.1016/j.tcsw.2023.100115 -
Italian Journal of Dermatology and... Oct 2023The oral mucosa can be involved in a wide variety of mucocutaneous conditions that may present primarily in the mouth or affect other cutaneous or mucosal sites. Many of... (Review)
Review
The oral mucosa can be involved in a wide variety of mucocutaneous conditions that may present primarily in the mouth or affect other cutaneous or mucosal sites. Many of these conditions are immune mediated and typically present as inflammatory mucosal pathology. Patients experiencing such conditions usually seek medical evaluation and treatment due to the associated pain and discomfort and occasionally taste disturbance or dysphagia and the overall deterioration in the oral health-related quality of life. These conditions share some common features and there could be some overlapping in their clinical presentation, which can lead to delays in diagnosis and proper management of patients. Clinicians dealing with such disorders, including dermatologists, need to be aware of the oral manifestations of mucocutaneous conditions, their clinical features, underlying mechanisms, diagnostic approaches, and treatment options, as well as the recent advances in the research on these conditions. This review provides a comprehensive, evidence-based reference for clinicians, with updated insights into a group of immune mediated conditions known to cause oral mucosal pathology. Part one will cover oral lichen planus, erythema multiforme and systemic lupus erythematosus, while part two will cover pemphigus vulgaris and mucous membrane pemphigoid, recurrent aphthous stomatitis, in addition to the less common disorders linear IgA disease, dermatitis herpetiformis and epidermolysis bullosa.
Topics: Humans; Mouth Mucosa; Mouth Diseases; Quality of Life; Stomatitis, Aphthous; Pemphigus
PubMed: 37916401
DOI: 10.23736/S2784-8671.23.07676-4