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Journal of Integrative Plant biology 2025年第1期67卷 87-100页

作者： Yael Hacham Alex Kaplan Elad Cohen Maayan Gal Rachel Amir Laboratory of Plant Science MigalGalilee Research InstituteKiryat Shmona 11016Israel Tel-Hai College Upper Galilee 11016Israel Department of oral biology Goldschleger School of Dental MedicineFaculty of MedicineTel Aviv UniversityTel Aviv 6997801Israel

Cysteine is the precursor for the biosynthesis of glutathione,a key stress-protective metabolite,and methionine,which is imperative for cell growth and protein *** exact mechanism that governs the routing of cysteine toward glutathione or methionine during stresses remains *** study reveals that under oxidative stress,methionine and glutathione compete for cysteine and that the increased oxidized glutathione(GSSG)levels under stress hinder methionine ***,we find that inhibition occurs as GSSG binds to and accelerates the degradation of cystathionineγ-synthase,a key enzyme in the methionine synthesis ***,this leads to a reduction in the flux toward methionine-derived metabolites and redirects cysteine utilization toward glutathione,thereby enhancing plant *** study suggests a novel regulatory feedback loop involving glutathione,methionine,and cysteine,shedding light on the plant stress response and the adaptive rerouting of *** findings offer new insights into the intricate balance of growth and protection in plants and its impact on their nutritional value due to low methionine levels under stress.

关键词： cystathionineγ-synthase(CGS) cysteine glutathione metabolic competition methionine oxidative stress sulfur metabolism tobacco

cGAS-STING: mechanisms and therapeutic opportunities

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Science China Life Sciences 2025年

作者： Mengyuan Zhang Changxin Wu Defen Lu Xing Wang Guijun Shang Shanxi Medical University School and Hospital of Stomatology Shanxi Province Key Laboratory of oral Diseases Prevention and New Materials The Key Laboratory of Medical Molecular Cell biology of Shanxi Province Institutes of Biomedical Sciences Shanxi University College of Life Sciences Shanxi Agricultural University

The cGAS-STING pathway plays a crucial role in the innate immune system by detecting mislocalized double-stranded DNA(dsDNA) in the cytoplasm and triggering downstream signal transduction. Understanding the mechanisms by which cGAS and STING operate is vital for gaining insights into the biology of this pathway. This review provides a detailed examination of the structural features of cGAS and STING proteins, with a particular emphasis on their activation and inhibition mechanisms. We also discuss the novel discovery of STING functioning as an ion channel. Furthermore, we offer an overview of key agonists and antagonists of cGAS and STING, shedding light on their mechanisms of action. Deciphering the molecular intricacies of the cGAS-STING pathway holds significant promise for the development of targeted therapies aimed at maintaining immune homeostasis within both innate and adaptive immunity.

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Intra-tumoral bacteria in head and neck cancer: holistic integrative insight

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Cancer biology & Medicine 2025年第02期 113-136页

作者： Yucheng Meng Jiaru Deng Weiwei Deng Zhijun Sun State Key Laboratory of oral & Maxillofacial Reconstruction and Regeneration Key Laboratory of Oral Biomedicine Ministry of Education Hubei Key Laboratory of Stomatology School & Hospital of Stomatology Frontier Science Center for Immunology and Metabolism Taikang Center for Life and Medical Sciences Wuhan University Department of oral & Maxillofacial Head Neck Oncology School & Hospital of Stomatology Wuhan University

Intra-tumoral bacteria are pivotal in the initiation and progression of head and neck squamous cell carcinoma(HNSCC), exerting a significant influence on tumor cell biology, immune responses, and the tumor microenvironment(TME). Different types and distribution of bacteria threaten the balance of metabolism and the immune environment of tumor cells. Taking advantage of this disrupted homeostasis, intra-tumoral bacteria stimulate the secretion of metabolites or influence specific immune cell types to produce inflammatory or chemokines, thereby influencing the anti-tumor immune response while regulating the level of inflammation and immunosuppression within the TME. Some intra-tumoral bacteria are used as diagnostic and prognostic markers in clinical practice. Based on the unique characteristics of bacteria, the use of engineered bacteria and outer membrane vesicles for drug delivery and biological intervention is a promising new therapeutic strategy. The presence of intra-tumoral bacteria also makes chemoradiotherapy tolerable, resulting in a poor treatment effect. However, due to the immune-related complexity of intra-tumoral bacteria, there may be unexpected effects in immunotherapy. In this review the patterns of intra-tumoral bacteria involvement in HNSCC are discussed, elucidating the dual roles, while exploring the relevance to anti-tumor immune responses in the clinical context and the prospects and limitations of the use of bacteria in targeted therapy.

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Dental pulp stem cells stimulate neuronal differentiation of PC12 cells

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Neural Regeneration Research 2021年第9期16卷 1821-1828页

作者： Nessma Sultan Laila E.Amin Ahmed R.Zaher Mohammed E.Grawish Ben A.Scheven School of Dentistry Oral BiologyCollege of Medical and Dental SciencesUniversity of BirminghamBirminghamUK Department of oral biology Faculty of DentistryMansoura UniversityEgypt Faculty of Dentistry Horus UniversityNew DamiettaEgypt Department of oral biology Faculty of Oral and Dental MedicineDelta University for Science and TechnologyMansouraEgypt

Dental pulp stem cells(DPSCs) secrete neurotrophic factors which may play an important therapeutic role in neural development, maintenance and repair. To test this hypothesis, DPSCs-conditioned medium(DPSCs-CM) was collected from 72 hours serum-free DPSCs cultures. The impact of DPSCs-derived factors on PC12 survival, growth, migration and differentiation was investigated. PC12 cells were treated with nerve growth factor(NGF), DPSCs-CM or co-cultured with DPSCs using Transwell inserts for 8 days. The number of surviving cells with neurite outgrowths and the length of neurites were measured by image analysis. Immunocytochemical staining was used to evaluate the expression of neuronal markers NeuN, microtubule associated protein 2(MAP-2) and cytoskeletal marker βIII-tubulin. Gene expression levels of axonal growth-associated protein 43 and synaptic protein Synapsin-I, NeuN, MAP-2 and βIII-tubulin were analysed by quantitative polymerase chain reaction(qRT-PCR). DPSCs-CM was analysed for the neurotrophic factors(NGF, brain-derived neurotrophic factor [BDNF], neurotrophin-3, and glial cell-derived neurotrophic factor [GDNF]) by specific ELISAs. Specific neutralizing antibodies against the detected neurotrophic factors were used to study their exact role on PC12 neuronal survival and neurite outgrowth extension. DPSCs-CM significantly promoted cell survival and induced the neurite outgrowth confirmed by NeuN, MAP-2 and βIII-tubulin immunostaining. Furthermore, DPSCsCM was significantly more effective in stimulating PC12 neurite outgrowths than live DPSCs/PC12 co-cultures over the time studied. The morphology of induced PC12 cells in DPSCs-CM was similar to NGF positive controls;however, DPSCs-CM stimulation of cell survival was significantly higher than what was seen in NGF-treated cultures. The number of surviving PC12 cells treated with DPSCs-CM was markedly reduced by the addition of anti-GDNF, whilst PC12 neurite outgrowth was significantly attenuated by anti-NGF, an

关键词： brain-derived neurotrophic factor conditioned medium dental pulp stem cell glial cell line-derived nerve growth factor neurite outgrowth neurotrophic factor neurotrophin-3 phaeochromocytoma PC12 cell

Early therapeutic effect of platelet-rich fibrin combined with allogeneic bone marrow-derived stem cells on rats’ critical-sized mandibular defects

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World Journal of Stem Cells 2020年第1期12卷 55-69页

作者： Muhammad A Awadeen Fouad A Al-Belasy Laila E Ameen Mohamad E Helal Mohammed E Grawish Department of oral biology Faculty of Oral and Dental MedicineDelta University for Science and TechnologyMansoura 11152Egypt Department of oral Surgery and Anesthesia Faculty of Oral and Dental MedicineDelta University for Science and TechnologyMansoura 11152Egypt Department of oral biology Faculty of DentistryMansoura UniversityMansoura 35516Egypt

BACKGROUND Critically sized bone defects represent a significant challenge to orthopaedic surgeons *** defects generally result from severe trauma or resection of a whole large *** bone grafts are the current gold standard for the reconstruction of such ***,due to increased patient morbidity and the need for a second operative site,other lines of treatment should be *** find alternative unconventional therapies to manage such defects,bone tissue engineering using a combination of suitable bioactive factors,cells,and biocompatible scaffolds offers a promising new approach for bone *** To evaluate the healing capacity of platelet-rich fibrin(PRF)membranes seeded with allogeneic mesenchymal bone marrow-derived stem cells(BMSCs)on critically sized mandibular defects in a rat *** Sixty-three Sprague Dawley rats were subjected to bilateral bone defects of critical size in the mandibles created by a 5-mm diameter trephine *** were allocated to three equal groups of 21 rats *** I bone defects were irrigated with normal saline and designed as negative *** of group II were grafted with PRF membranes and served as positive controls,while defects of group III were grafted with PRF membranes seeded with allogeneic *** rats from each group were killed at 1,2 and 4 *** mandibles were dissected and prepared for routine haematoxylin and eosin(HE)staining,Masson's trichrome staining and CD68 immunohistochemical *** Four weeks postoperatively,the percentage area of newly formed bone was significantly higher in group III(0.88±0.02)than in groups I(0.02±0.00)and II(0.60±0.02).The amount of granulation tissue formation was lower in group III(0.12±0.02)than in groups I(0.20±0.02)and II(0.40±0.02).The number of inflammatory cells was lower in group III(0.29±0.03)than in groups I(4.82±0.08)and II(3.09±0.07).CONCLUSION Bone regenerative quality of critically sized mandibula

关键词： Platelet-rich fibrin membrane Bone marrow-derived stem cells Critical-sized mandibular defects Rats Histological and immunohistochemical staining

Exploring the potential application of dental pulp stem cells in neuroregenerative medicine

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Neural Regeneration Research 2022年第4期17卷 775-776页

作者： Nessma Sultan Ben A.Scheven Department of oral biology Faculty of DentistryMansoura UniversityMansouraEgypt School of Dentistry Oral BiologyCollege of Medical and Dental SciencesUniversity of BirminghamBirminghamUK

The trigeminal nerve and its peripheral branches are susceptible to injury in the dental practice due to surgical removal of impacted third molars and placement of dental *** peripheral trigeminal nerve injuries can undergo spontaneous regeneration,some injuries may be permanent with varying degrees of continued sensory impairment and neuropathic pain ranging from mild numbness to complete anaesthesia(Tay and Zuniga,2007).Adult neurons require continued neurotrophic support from surrounding cells to sustain neural viability,inhibit death-inducing pathways activating a variety of cell survival pathways(Zheng and Quirion,2004).

关键词： injuries continued permanent

Gingival-derived mesenchymal stem cells:An endless resource for regenerative dentistry

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World Journal of Stem Cells 2018年第9期10卷 116-118页

作者： Mohammed E Grawish Department of oral biology Faculty of DentistryMansoura University

The gingiva, the masticatory portion of the oral mucosa, is excised and discarded frequently during routine dental treatments and following tooth extraction, dental crown lengthening, gingivectomy and periodontal surgeries. Subsequent to excision, healing eventually happens in a short time period after gingival surgery. Clinically, the gingival tissue can be collected very easily and, in the laboratory, it is also very easy to isolate gingival-derived mesenchymal stem cells (GMSCs) from this discarded gingival tissue. GMSCs, a stem cell population within the lamina propria of the gingival tissue, can be isolated from attached and free gingiva, inflamed gingival tissu-es, and from hyperplastic gingiva. Comparatively, they constitute more attractive alternatives to other dental-derived mesenchymal stem cells due to the availability and accessibility of gingival tissues. They have unique immunomodulatory functions and well-documented self-renewal and multipotent differentiation properties. They display positive signals for Stro-1, Oct-4 and SSEA-4 pluripotency-associated markers, with some co-expre-ssing Oct4/Stro-1 or Oct-4/SSEA-4. They should be considered as the best stem cell source for cell-based therapies and regenerative dentistry. The clinical use of GMSCs for regenerative dentistry represents an attrac-tive therapeutic modality. However, numerous biological and technical challenges need to be addressed prior to considering transplantation approaches of GMSCs as clinically realistic therapies for humans.

关键词： Gingival-derived mesenchymal stem cells Regenerative dentistry Lamina propria of the gingiva Gingiva Stem cell therapy

Human dental pulp stem/stromal cells in clinical practice

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World Journal of Stem Cells 2024年第2期16卷 54-57页

作者： Mohammed E Grawish Department of oral biology Faculty of DentistryMansoura UniversityMansoura 35561Egypt Department of oral biology Faculty of Oral and Dental MedicineDelta University for Science and TechnologyMansoura 11152Egypt

Dental pulp stem/stromal cells(DPSCs)are fibroblast-like,neural crest-derived,and multipotent cells that can differentiate into several *** are relatively easy to isolate from healthy and inflamed pulps,with little ethical concerns and can be successfully cryopreserved and *** therapeutic effects of DPSCs derived from animal or human sources have been extensively studied through in-vitro and in-vivo animal experiments and the findings indicated that DPSCs are effective not only for dental diseases but also for systemic *** that translational research is a critical step through which the fundamental scientific discoveries could be translated into applicable diagnostics and therapeutics that directly benefit humans,several clinical studies were carried out to generate evidence for the efficacy and safety of autogenous or allogeneic human DPSCs(hDPSCs)as a treatment modality for use in cell-based therapy,regenerative medicine/dentistry and tissue *** clinical medicine,hDPSCs were effective for treating acute ischemic stroke and human exfoliated deciduous teeth-conditioned medium(SHED-CM)repaired vascular damage of the corpus cavernous,which is the main cause of erectile *** in clinical dentistry,autologous SHED was able to rege-nerate necrotic dental pulp after implantation into injured teeth,and micrografts enriched with autologous hDPSCs and collagen sponge were considered a treatment option for human intrabony *** contrast,hDPSCs did not add a significant regenerative effect when they were used for the treatment of post-extraction ***-scale clinical studies across diverse populations are still lacking to provide robust evidence on the safety and efficacy of hDPSCs as a new treatment option for various human diseases including dental-related problems.

关键词： Dental pulp stem/stromal cells Human clinical studies Regenerative medicine Regenerative dentistry Cell-based therapy

Bone-conditioned medium contributes to initiation and progression of osteogenesis by exhibiting synergistic TGF-β1/BMP-2 activity

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International Journal of oral Science 2018年第4期10卷 203-211页

作者： Maria B.Asparuhova Jordi Caballé-Serrano Daniel Buser Vivianne Chappuis Laboratory of oral Cell biology School of Dental MedicineUniversity of Bern Department of oral Surgery and Stomatology School of Dental MedicineUniversity of Bern Department of oral and Maxillofacial Surgery School of Dental MedicineUniversitat Internacional de Catalunya

Guided bone regeneration (GBR) often utilizes a combination of autologous bone grafts, deproteinized bovine bone mineral(DBBM), and collagen membranes. DBBM and collagen membranes pre-coated with bone-conditioned medium (BCM) extracted from locally harvested autologous bone chips have shown great regenerative potential in GBR. However, the underlying molecular mechanism remains largely unknown. Here, we investigated the composition of BCM and its activity on the osteogenic potential of mesenchymal stromal cells. We detected a fast and significant (P <0.001) release of transforming growth factor-β1 (TGF-β1) from autologous bone within 10 min versus a delayed bone morphogenetic protein-2 (BMP-2) release from 40 min onwards. BCMs harvested within short time periods (10, 20, or 40 min), corresponding to the time of a typical surgical procedure, significantly increased the proliferative activity and collagen matrix production of BCM-treated cells. Long-term (1, 3, or 6 days)-extracted BCMs promoted the later stages of osteoblast differentiation and maturation. Short-term-extracted BCMs, in which TGF-β1 but no BMP-2was detected, reduced the expression of the late differentiation marker osteocalcin. However, when both growth factors were present simultaneously in the BCM, no inhibitory effects on osteoblast differentiation were observed, suggesting a synergistic TGF-β1/BMP-2 activity. Consequently, in cells that were co-stimulated with recombinant TGF-β1 and BMP-2, we showed a significant stimulatory and dose-dependent effect of TGF-β1 on BMP-2-induced osteoblast differentiation due to prolonged BMP signaling and reduced expression of the BMP-2 antagonist noggin. Altogether, our data provide new insights into the molecular mechanisms underlying the favorable outcome from GBR procedures using BCM, derived from autologous bone grafts.

关键词： Bone-conditioned medium contributes to initiation and progression of osteogenesis by exhibiting synergistic TGF BMP-2 activity

Pulmonary CD103+ dendritic cells: key regulators of immunity against infection

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Cellular & Molecular Immunology 2020年第6期17卷 670-671页

作者： Sudhanshu Shekhar Xi Yang Institute of oral biology University of OsloOsloNorway Department of Immunology University of ManitobaWinnipegCanada

Since the discovery of dendritic cells(DCs)by the Nobel laureate Professor Ralph Steinman et *** 1973,a plethora of literature has accumulated on the functional roles of DCs in humans and animal models.1 DCs are involved in the innate sensing and modulation of adaptive immunity to ***103+DCs constitute a classical nonlymphoid DC subset that has an important role in generating immunity and maintaining tolerance.2 Pulmonary CD103+DCs(CD103+PDCs),which reside in close association with the airway epithelium,are particularly critical in controlling Tcell immunity against lung infections.2,3 In this article,we discuss recent evidence that shines light on the role and mechanism of CD103+PDCs in modulating CD8+and CD4+T-cell responses against various pathogens,including bacteria and viruses.A deeper understanding of CD103+PDC function may provide new translational avenues for the development of vaccines and therapeutics against infectious diseases.

关键词： CD103 immunity generating