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Cell Reports Jun 2024Cell functions rely on intracellular transport systems distributing bioactive molecules with high spatiotemporal accuracy. The endoplasmic reticulum (ER) tubular network...
Cell functions rely on intracellular transport systems distributing bioactive molecules with high spatiotemporal accuracy. The endoplasmic reticulum (ER) tubular network constitutes a system for delivering luminal solutes, including Ca, across the cell periphery. How the ER structure enables this nanofluidic transport system is unclear. Here, we show that ER membrane-localized reticulon 4 (RTN4/Nogo) is sufficient to impose neurite outgrowth inhibition in human cortical neurons while acting as an ER morphoregulator. Improving ER transport visualization methodologies combined with optogenetic Ca dynamics imaging and in silico modeling, we observed that ER luminal transport is modulated by ER tubule narrowing and dilation, proportional to the amount of RTN4. Excess RTN4 limited ER luminal transport and Ca release, while RTN4 elimination reversed the effects. The described morphoregulatory effect of RTN4 defines the capacity of the ER for peripheral Ca delivery for physiological releases and thus may constitute a mechanism for controlling the (re)generation of neurites.
PubMed: 38955182
DOI: 10.1016/j.celrep.2024.114357 -
PeerJ 2024Mesenchymal stem cells (MSCs) are increasingly recognized for their regenerative potential. However, their clinical application is hindered by their inherent...
BACKGROUND
Mesenchymal stem cells (MSCs) are increasingly recognized for their regenerative potential. However, their clinical application is hindered by their inherent variability, which is influenced by various factors, such as the tissue source, culture conditions, and passage number.
METHODS
MSCs were sourced from clinically relevant tissues, including adipose tissue-derived MSCs (ADMSCs, = 2), chorionic villi-derived MSCs (CMMSCs, = 2), amniotic membrane-derived MSCs (AMMSCs, = 3), and umbilical cord-derived MSCs (UCMSCs, = 3). Passages included the umbilical cord at P0 (UCMSCP0, = 2), P3 (UCMSCP3, = 2), and P5 (UCMSCP5, = 2) as well as the umbilical cord at P5 cultured under low-oxygen conditions (UCMSCP5L, = 2).
RESULTS
We observed that MSCs from different tissue origins clustered into six distinct functional subpopulations, each with varying proportions. Notably, ADMSCs exhibited a higher proportion of subpopulations associated with vascular regeneration, suggesting that they are beneficial for applications in vascular regeneration. Additionally, CMMSCs had a high proportion of subpopulations associated with reproductive processes. UCMSCP5 and UCMSCP5L had higher proportions of subpopulations related to female reproductive function than those for earlier passages. Furthermore, UCMSCP5L, cultured under low-oxygen (hypoxic) conditions, had a high proportion of subpopulations associated with pro-angiogenic characteristics, with implications for optimizing vascular regeneration.
CONCLUSIONS
This study revealed variation in the distribution of MSC subpopulations among different tissue sources, passages, and culture conditions, including differences in functions related to vascular and reproductive system regeneration. These findings hold promise for personalized regenerative medicine and may lead to more effective clinical treatments across a spectrum of medical conditions.
Topics: Mesenchymal Stem Cells; Humans; Umbilical Cord; Female; Adipose Tissue; Cells, Cultured; Chorionic Villi; Amnion; Cell Differentiation
PubMed: 38952966
DOI: 10.7717/peerj.17616 -
Biomaterials Research 2024One of the bacterial infections caused by tympanic membrane perforation is otitis media (OM). Middle ear inflammation causes continuous pain and can be accompanied by...
One of the bacterial infections caused by tympanic membrane perforation is otitis media (OM). Middle ear inflammation causes continuous pain and can be accompanied by aftereffects such as facial nerve paralysis if repeated chronically. Therefore, it is necessary to develop an artificial tympanic membrane (TM) that can effectively regenerate the eardrum due to the easy implantation and removal of OM inflammation. In this study, we synthesized hydrogel by mixing gelatin and polyacrylamide. Cefuroxime sodium salt was then incorporated into this hydrogel to both regenerate the TM and treat OM. Cytotoxicity experiments confirmed the biocompatibility of hydrogels equipped with antibiotics, and we conducted drug release and antibacterial experiments to examine continuous drug release. Through experiments, we have verified the excellent biocompatibility, drug release ability, and antibacterial effectiveness of hydrogel. It holds the potential to serve as an effective strategy for treating OM and regenerating TM as a drug delivery substance.
PubMed: 38952716
DOI: 10.34133/bmr.0049 -
Biomaterials Research 2024Intervertebral discs (IVDs) have a limited self-regenerative capacity and current strategies for IVD regeneration are unsatisfactory. Recent studies showed that small...
Intervertebral discs (IVDs) have a limited self-regenerative capacity and current strategies for IVD regeneration are unsatisfactory. Recent studies showed that small extracellular vesicles derived from M2 macrophage cells (M2-sEVs) inhibited inflammation by delivery of various bioactive molecules to recipient cells, which indicated that M2-sEVs may offer a therapeutic strategy for the repair of IVDs. Herein, we investigated the roles and mechanisms of M2-sEVs on IVD regeneration. The in vitro results demonstrated that M2-sEVs inhibited pyroptosis, preserved cellular viability, and promoted migration of nucleus pulposus cells (NPCs). Bioinformatics analysis and verification experiments of microRNA (miR) expression showed that miR-221-3p was highly expressed in M2-sEVs. The mechanism of action was explored and indicated that M2-sEVs inhibited pyroptosis of NPCs through transfer of miR-221-3p, which suppressed the expression levels of phosphatase and tensin homolog and NOD-, LRR-, and pyrin domain-containing protein 3. Moreover, we fabricated decellularized ECM-hydrogel (dECM) for sustained release of M2-sEVs, which exhibited biocompatibility and controlled release properties. The in vivo results revealed that dECM-hydrogel containing M2-sEVs (dECM/M2-sEVs) delayed the degeneration of intervertebral disc degeneration (IDD) models. In addition to demonstrating a promising therapeutic for IDD, this study provided valuable data for furthering the understanding of the roles and mechanisms of M2-sEVs in IVD regeneration.
PubMed: 38952714
DOI: 10.34133/bmr.0047 -
International Journal of Nanomedicine 2024Implants are widely used in the field of orthopedics and dental sciences. Titanium (TI) and its alloys have become the most widely used implant materials, but...
BACKGROUND
Implants are widely used in the field of orthopedics and dental sciences. Titanium (TI) and its alloys have become the most widely used implant materials, but implant-associated infection remains a common and serious complication after implant surgery. In addition, titanium exhibits biological inertness, which prevents implants and bone tissue from binding strongly and may cause implants to loosen and fall out. Therefore, preventing implant infection and improving their bone induction ability are important goals.
PURPOSE
To study the antibacterial activity and bone induction ability of titanium-copper alloy implants coated with nanosilver/poly (lactic-co-glycolic acid) (NSPTICU) and provide a new approach for inhibiting implant-associated infection and promoting bone integration.
METHODS
We first examined the in vitro osteogenic ability of NSPTICU implants by studying the proliferation and differentiation of MC3T3-E1 cells. Furthermore, the ability of NSPTICU implants to induce osteogenic activity in SD rats was studied by micro-computed tomography (micro-CT), hematoxylin-eosin (HE) staining, masson staining, immunohistochemistry and van gieson (VG) staining. The antibacterial activity of NSPTICU in vitro was studied with gram-positive and gram-negative bacteria. was used as the test bacterium, and the antibacterial ability of NSPTICU implanted in rats was studied by gross view specimen collection, bacterial colony counting, HE staining and Giemsa staining.
RESULTS
Alizarin red staining, alkaline phosphatase (ALP) staining, quantitative real-time polymerase chain reaction (qRT-PCR) and western blot analysis showed that NSPTICU promoted the osteogenic differentiation of MC3T3-E1 cells. The in vitro antimicrobial results showed that the NSPTICU implants exhibited better antibacterial properties. Animal experiments showed that NSPTICU can inhibit inflammation and promote the repair of bone defects.
CONCLUSION
NSPTICU has excellent antibacterial and bone induction ability, and has broad application prospects in the treatment of bone defects related to orthopedics and dental sciences.
Topics: Animals; Anti-Bacterial Agents; Osteogenesis; Polylactic Acid-Polyglycolic Acid Copolymer; Mice; Staphylococcus aureus; Coated Materials, Biocompatible; Rats, Sprague-Dawley; Escherichia coli; Cell Differentiation; Prostheses and Implants; Alloys; Rats; Titanium; Silver; Cell Proliferation; Copper; Male; X-Ray Microtomography; Cell Line; Metal Nanoparticles
PubMed: 38952675
DOI: 10.2147/IJN.S456906 -
Frontiers in Bioengineering and... 2024
PubMed: 38952669
DOI: 10.3389/fbioe.2024.1440925 -
Materials Today. Bio Jun 2024Clinical treatment of diabetic refractory ulcers is impeded by chronic inflammation and cell dysfunction associated with wound healing. The significant clinical...
Clinical treatment of diabetic refractory ulcers is impeded by chronic inflammation and cell dysfunction associated with wound healing. The significant clinical application of bFGF in wound healing is limited by its instability . Sulfur has been applied for the treatment of skin diseases in the clinic for antibiosis. We previously found that sulfur incorporation improves the ability of selenium nanoparticles to accelerate wound healing, yet the toxicity of selenium still poses a risk for its clinical application. To obtain materials with high pro-regeneration activity and low toxicity, we explored the mechanism by which selenium-sulfur nanoparticles aid in wound healing via RNA-Seq and designed a nanoparticle called Nano-S@bFGF, which was constructed from sulfur and bFGF. As expected, Nano-S@bFGF not only regenerated zebrafish tail fins and promoted skin wound healing but also promoted skin repair in diabetic mice with a profitable safety profile. Mechanistically, Nano-S@bFGF successfully coactivated the FGFR and Hippo signalling pathways to regulate wound healing. Briefly, the Nano-S@bFGF reported here provides an efficient and feasible method for the synthesis of bioactive nanosulfur and bFGF. In the long term, our results reinvigorated efforts to discover more peculiar unique biofunctions of sulfur and bFGF in a great variety of human diseases.
PubMed: 38952539
DOI: 10.1016/j.mtbio.2024.101104 -
Frontiers in Molecular Neuroscience 2024
PubMed: 38952420
DOI: 10.3389/fnmol.2024.1428164 -
Journal of Cardiothoracic Surgery Jul 2024Myocardial ischemia-reperfusion injury (MIRI) is defined as the restoration of blood flow to the myocardium after a brief interruption of blood supply, causing more...
BACKGROUND
Myocardial ischemia-reperfusion injury (MIRI) is defined as the restoration of blood flow to the myocardium after a brief interruption of blood supply, causing more severe damage to the ischemic myocardium. However, currently, reperfusion therapy is the preferred therapy for ischemic cardiomyopathy, which undoubtedly causes MIRI, and thus it has become a challenging issue affecting the prognosis of coronary artery disease.
METHODS
A search was conducted in the Web of Science Core Collection database for papers relevant to MIRI therapy published between 1 January 2000 and 1 October 2023. Bibliometric analyses were performed using VOSviewer and CiteSpace to elucidate the progress and hotspots.
RESULTS
3304 papers from 64 countries, 2134 research institutions and 13,228 authors were enrolled in the study. Of these, China contributed the most papers and had the biggest impact, while the United States had the most extensive partnership. The Fourth Military Medical University was the primary research institution. The most valuable authors include Chattipakorn, Nipon, Chattipakorn, Siriporn c, Yang, Jian and Yang, Yang.
CONCLUSION
Over the past 20 years, research on MIRI therapies has made significant strides. Further studies are necessary to explore the interactions between various therapeutic options. Future investigations will emphasize nanocarriers, cardiac regeneration, and stem cell therapies. Our study identifies MIRI research hotspots from a bibliometric perspective, forecasts future trends, and offers fresh insights into MIRI therapy research.
Topics: Bibliometrics; Humans; Myocardial Reperfusion Injury
PubMed: 38951938
DOI: 10.1186/s13019-024-02924-3 -
Journal of Experimental & Clinical... Jul 2024Leukocyte Ig-like receptor B family 4 (LILRB4) as an immune checkpoint on myeloid cells is a potential target for tumor therapy. Extensive osteolytic bone lesion is the...
BACKGROUND
Leukocyte Ig-like receptor B family 4 (LILRB4) as an immune checkpoint on myeloid cells is a potential target for tumor therapy. Extensive osteolytic bone lesion is the most characteristic feature of multiple myeloma. It is unclear whether ectopic LILRB4 on multiple myeloma regulates bone lesion.
METHODS
The conditioned medium (CM) from LILRB4-WT and -KO cells was used to analyze the effects of LILRB4 on osteoclasts and osteoblasts. Xenograft, syngeneic and patient derived xenograft models were constructed, and micro-CT, H&E staining were used to observe the bone lesion. RNA-seq, cytokine array, qPCR, the activity of luciferase, Co-IP and western blotting were used to clarify the mechanism by which LILRB4 mediated bone damage in multiple myeloma.
RESULTS
We comprehensively analyzed the expression of LILRB4 in various tumor tissue arrays, and found that LILRB4 was highly expressed in multiple myeloma samples. The patient's imaging data showed that the higher the expression level of LILRB4, the more serious the bone lesion in patients with multiple myeloma. The conditioned medium from LILRB4-WT not -KO cells could significantly promote the differentiation and maturation of osteoclasts. Xenograft, syngeneic and patient derived xenograft models furtherly confirmed that LILRB4 could mediate bone lesion of multiple myeloma. Next, cytokine array was performed to identify the differentially expressed cytokines, and RELT was identified and regulated by LILRB4. The overexpression or exogenous RELT could regenerate the bone damage in LILRB4-KO cells in vitro and in vivo. The deletion of LILRB4, anti-LILRB4 alone or in combination with bortezomib could significantly delay the progression of bone lesion of multiple myeloma.
CONCLUSIONS
Our findings indicated that LILRB4 promoted the bone lesion by promoting the differentiation and mature of osteoclasts through secreting RELT, and blocking LILRB4 singling pathway could inhibit the bone lesion.
Topics: Multiple Myeloma; Humans; Mice; Animals; Signal Transduction; Receptors, Immunologic; NF-kappa B; Membrane Glycoproteins; Cell Line, Tumor; Osteoclasts; Xenograft Model Antitumor Assays
PubMed: 38951916
DOI: 10.1186/s13046-024-03110-y