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Background To assess the anatomical relationship and age-related variability of the anatomies in the pre-tracheal space in elderly patients with head and neck cancers and to guide tracheotomy with clinical evidence for either planned or improvised procedures. Methods From January 2019 to February 2022, hospitalized head and neck cancer patients aged over 65 years (127 cases) and under 65 years (74 cases) were enrolled in this study as the observation and the control groups, respectively. All these patients received contrast-enhanced CT scans, ablative operations and tracheotomies for primary head and neck cancers. The radiographic reconstructions of vascular morphologies were compared, focusing on three target vessels: anterior jugular veins (AJVs), innominate arteries (IAs) and inferior thyroid plexuses (ITVPs). The upper locations of the isthmus, and the largest diameters of thyroid glands were compared as well. In addition, surgical exposure of those vessels was recorded during tracheostomies to verify these radiologic findings. The tracheotomy procedure-related complications were also compared. Results A total number of 201 patients (115 males and 86 females) were identified in this study. The mean age of the elderly group reached 72.0 years (range: 65–87 years), most of whom (41.7%) were with oral or oropharyngeal cancer. The proportion for single-branch type AJVs in the elderly group (11.9%) was higher than that in the young counterpart (8.2%), though no statistical difference was found (P = 0.701). Radiologically speaking, the IAs were categorized as the low-bifurcation (104 cases, 51.7%), high-bifurcation (n = 37, 18.4%), high-platform (27, 13.4%), low-platform (30, 14.9%) and variant types (3, 1.5%). Age-related changes of IA types were found between the elderly and the young groups (P n=0.59, P

Background: Trigeminal neuralgia is a typical kind of neuropathic pain featured with severe and recurrent pain attacks along the areas innervated by trigeminal nerve. Although mechanical injuries caused by vessels compression is highly related to the pathogenesis, the underlying molecular mechanism remains unclear. Methods: We constructed chronic constriction to infraorbital nerve (CCI) on Sprague Dawley rats, after which spontaneous pain and mechanical allodynia related behaviors were measured. Transcriptome of trigeminal ganglion (TG) affected by CCI were analyzed to select the related signaling pathway and genes. We examined the receptor-interacting serine/threonine-protein kinase 1 (RIPK1) and domain-like receptor protein 3 (NLRP3) expression in the trigeminal ganglion by western blotting and RT-PCR; studied the location of RIPK1 and NLRP3 expression by performing immunofluorescence. Necrostatin-1, the specific antagonist of RIPK1, was administered to identify the effect of RIPK1 inhibition on NLRP3 expression. Results: We identified mechanical allodynia within the whisker pad area after CCI. RNA-sequencing indicated that NLRP3 levels in the trigeminal ganglion were higher in CCI groups compared to the control group and MAPK signaling pathway was up-regulated after CCI. We also identified an increase in overall reactivity of RIPK1 in trigeminal ganglia after the surgery. A significant proportion of RIPK1+ cells in the TG of CCI rats colocalized with the neuron cells. RT-PCR result shows the expression of NLRP3 also increased following RIPK1 activation. The results from immunofluorescence staining revealed that NLRP3 was upregulated in TG neuron cells. Also, when RIPK1 is inhibited by Nec-1, NLRP3 expression in neurons from CCI rats also decreased. Nec-1 can alleviate the demyelination of TG and mechanical allodynia after CCI. Compared to control group, RIPK1 expression is down-regulated after Nec-1 injection, followed by a decreasing in NLRP3 expression. Conclusions: This study demonstrates RIPK1 in TG neurons is activated when nerves are mechanically injuried, leading to the over-expression of NLRP3 inflammasome by activating MAPK signaling pathway. The subsequent cascade of inflammatory feedback and pain signal transmission led to the occurrence of trigeminal neuralgia.

Cancer immunotherapy, which reprograms a patient's own immune system to eradicate cancer cells, has been demonstrated as a promising therapeutic strategy clinically. Immune checkpoint blockade (ICB) therapies, cytokine therapies, cancer vaccines, and chimeric antigen receptor (CAR) T cell therapies utilize immunotherapy techniques to relieve tumor immune suppression and/or activate cellular immune responses to suppress tumor growth, metastasis and recurrence. However, systemic administration is often hampered by limited drug efficacy and adverse side effects due to nonspecific tissue distribution of immunotherapeutic agents. Advancements in local scaffold-based delivery systems facilitate a controlled release of therapeutic agents into specific tissue sites through creating a local drug reservoir, providing a potent strategy to overcome previous immunotherapy limitations by improving site-specific efficacy and minimizing systemic toxicity. In this review, we summarized recent advances in local scaffold-assisted delivery of immunotherapeutic agents to reeducate the immune system, aiming to amplify anticancer efficacy and minimize immune-related adverse events. Additionally, the challenges and future perspectives of local scaffold-assisted cancer immunotherapy for clinical translation and applications are discussed.

Full-thickness skin regeneration is still a clinical challenge for skin defects. Porcine small intestinal submucosa (SIS) has been exploited as a new scaffold for tissue reconstruction due to its excellent biocompatibility and ease of handling and modification. However, the application of SIS is dramatically impeded by its compact structure. Thus, a strategy for improving this property of SIS is highly desirable. Herein, SIS was recross-linked by a four-arm polyethylene glycol (fa-PEG) with succinimidyl glutarate-terminated branches into a three-dimensional (3D) bioactive sponge (SIS-PEG), which possessed porous 3D frameworks to mimic the structure of skin. The addition of a suitable proportion of fa-PEG endowed SIS with a uniform pore size, outstanding bioactivity, and flexible shape to promote a rapid healing of a mouse skin defect. Compared with SIS, the bioactive SIS-PEG sponge exhibited excellent mechanical stability and was less prone to collagenase degradation. Moreover, SIS-PEG provided a minimally invasive way to deliver stem cells for in situ wound repair. Remarkably, in vivo evaluation demonstrated that dissociated epidermal and dermal cells loaded with SIS-PEG could form reconstituted skin with regenerated hair after 21 days of treatment. The SIS-PEG bioactive sponge exhibited great potential for skin tissue engineering.

BackgroundTranscription factors, including trihelix transcription factors, play vital roles in various growth and developmental processes and in abiotic stress responses in plants. Thetrihelixgene has been systematically studied in some dicots and monocots, includingArabidopsis,tomato, chrysanthemum, soybean, wheat, corn, rice, and buckwheat. However, there are no related studies on sorghum.ResultsIn this study, a total of 40 sorghum trihelix (SbTH) genes were identified based on the sorghum genome, among which 34 were located in the nucleus, 5 in the chloroplast, 1 (SbTH38) in the cytoplasm, and 1 (SbTH23) in the extracellular membrane. Phylogenetic analysis of theSbTHgenes andArabidopsisand ricetrihelixgenes indicated that the genes were clustered into seven subfamilies: SIP1, GTγ, GT1, GT2, SH4, GTSb8, and orphan genes. TheSbTHgenes were located in nine chromosomes and none on chromosome 10. One pair of tandem duplication gene and seven pairs of segmental duplication genes were identified in theSbTHgene family. By qPCR, the expression of 14 SbTH members in different plant tissues and in plants exposed to six abiotic stresses at the seedling stage were quantified. Except for the leaves in which the genes were upregulated after only 2 h exposure to high temperature, the 12 SbTHgenes were significantly upregulated in the stems of sorghum seedlings after 24 h under the other abiotic stress conditions. Among the selected genes,SbTH10/37/39were significantly upregulated, whereasSbTH32was significantly downregulated under different stress conditions.ConclusionsIn this study, we identified 40 trihelix genes in sorghum and found that gene duplication was the main force drivingtrihelixgene evolution in sorghum. The findings of our study serve as a basis for further investigation of the functions ofSbTHgenes and providing candidate genes for stress-resistant sorghum breeding programmes and increasing sorghum yield.

Adipose-derived stem cell (ADSC) transplantation has emerged as a potential tool for the treatment of cardiovascular disease and skin wounds. However, with a limited renewal capacity and the need for mass cells during the engraftment, strategies are needed to enhance ADSC proliferative capacity. In this study, we explored the effects of Exendin-4, a glucagon-like peptide-1 analog, on the growth of ADSCs, focusing in particular on phosphatidylinositol 3-kinase (PI3K)-protein kinase B (Akt) and Wnt signaling pathways. Firstly, ADSCs were isolated and cultured in vitro. Then, flow cytometry demonstrated that ADSCs were positive for CD44, CD90 and CD29 but negative for CD31, CD34, and CD45. Exendin-4 (0–200 nM) treatment increased ADSC proliferation. In order to examine specific signaling pathways, a western blotting assay was performed. Our results demonstrate that after treated with 50 nM Exendin-4 for 48 h, the phosphorylation of PI3K, Akt, and GSK3β were increased and phosphorylation of β-catenin was decreased. From these results, we concluded that PI3K-Akt and Wnt-β-catenin signaling pathways mediate Exendin-4 induced ADSC proliferation, the function of which might contribute to the regulation of ADSC proliferation. Our findings provided new insights into the function of the mechanisms underlying Exendin-4 of ADSCs.

// Yabing Dong 1, 2, * , Gaoyi Wu 3, * , Ting Zhu 1, 2, * , Hongyu Chen 1, 2 , Yong Zhu 1, 2 , Guoxiong Zhu 3 , Fabin Han 4 , Huaqiang Zhao 1 1 School of Stomatology, Shandong University, Wen Hua Xi Lu, Jinan City 250012, Shandong Province, China 2 Shandong Provincial Key Laboratory of Oral Tissue Regeneration, Wen Hua Xi Lu, Jinan City 250012, Shandong Province, China 3 Department of Stomatology, Jinan Military General Hospital, Shi Fan Lu, Jinan City 250031, Shandong Province, China 4 Center for Stem Cells and Regenerative Medicine, The Affiliated Liaocheng Hospital, Taishan Medical University, 252000, Shandong Province, China * These authors contributed equally to this work Correspondence to: Huaqiang Zhao, email: zhaohq@sdu.edu.cn Keywords: chronic sleep disturbance, angiogenesis, TMJ-OA, VEGF Received: November 22, 2016 Accepted: January 18, 2017 Published: January 28, 2017 ABSTRACT Chronic sleep disturbance (CSD) has been linked to the development of temporomandibular joint osteoarthritis (TMJ-OA). While the pathogenesis of TMJ-OA is unclear, recent studies indicate that osteochondral angiogenesis is important. We developed a rat model of CSD induced TMJ-OA to investigate the changes caused by sleep disturbance and to correlate them with vascular invasion in the TMJ. We found pathological alterations and an increased microvessel density in the rat TMJ following CSD. VEGF, Dll4 and p-ERK1/2, the expression of angiogenic factors, were highly expressed in the rat mandibular condylar cartilage and their expression increased with CSD. Furthermore, we show that VEGF-induce activation of ERK1/2, which in turn, increases Dll4 expression. Together, our results suggest that CSD can cause OA-like pathological alterations in the rat TMJ by increasing angiogenesis.

The noninvasive nature of photodynamic therapy (PDT) enables the preservation of organ function in cancer patients. However, PDT is impeded by hypoxia in the tumor microenvironment (TME) caused by high intracellular oxygen (O2) consumption and distorted tumor blood vessels. Therefore, increasing oxygen generation in the TME would be a promising methodology for enhancing PDT. Herein, we proposed a concept of ferroptosis-promoted PDT based on the biochemical characteristics of cellular ferroptosis, which improved the PDT efficacy significantly by producing reactive oxygen species (ROS) and supplying O2 sustainably through the Fenton reaction. In contrast to traditional strategies that increase O2 based on decomposition of limited concentration of hydrogen peroxide (H2O2), our methodology could maintain the concentration of H2O2 and O2 through the Fenton reaction. Methods: For its association with sensitivity to ferroptosis, solute carrier family 7 member 11 (SLC7A11) expression was characterized by bioinformatics analysis and immunohistochemistry of oral tongue squamous cell carcinoma (OTSCC) specimens. Afterwards, the photosensitizer chlorin e6 (Ce6) and the ferroptosis inducer erastin were self-assembled into a novel supramolecular Ce6-erastin nanodrug through hydrogen bonding and π-π stacking. Then, the obtained Ce6-erastin was extensively characterized and its anti-tumor efficacy towards OTSCC was evaluated both in vitro and in vivo. Results: SLC7A11 expression is found to be upregulated in OTSCC, which is a potential target for ferroptosis-mediated OTSCC treatment. Ce6-erastin nanoparticles exhibited low cytotoxicity to normal tissues. More significantly, The over-accumulated intracellular ROS, increased O2 concentration and inhibited SLC7A11 expression lead to enhanced toxicity to CAL-27 cells and satisfactory antitumor effects to xenograft tumour mouse model upon irradiation. Conclusion: Our ferroptosis promoted PDT approach markedly enhances anticancer actions by relieving hypoxia and promoting ROS production, thereby our work provides a new approach for overcoming hypoxia-associated resistance of PDT in cancer treatment.

Objective Parkinson's disease (PD), which is one of the most common neurodegenerative disorders, is characterized by the loss of dopamine (DA) neurons in the substantia nigra in the midbrain. Experimental and clinical studies have shown that fetal neural stem cells (NSCs) have therapeutic effects in neurological disorders. The aim of this study was to examine whether cells that were differentiated from NSCs had therapeutic effects in a rat model of PD. Methods NSCs were isolated from 14-week-old embryos and induced to differentiate into neurons, DA neurons, and glial cells, and these cells were characterized by their expression of the following markers: βIII-tubulin and microtubule-associated protein 2 (neurons), tyrosine hydroxylase (DA neurons), and glial fibrillary acidic protein (glial cells). After a 6-hydroxydopamine (6-OHDA)-lesioned rat model of PD was generated, the differentiated cells were transplanted into the striata of the 6-OHDA-lesioned PD rats. Results The motor behaviors of the PD rats were assessed by the number of apomorphine-induced rotation turns. The results showed that the NSCs differentiated in vitro into neurons and DA neurons with high efficiencies. After transplantation into the striata of the PD rats, the differentiated cells significantly improved the motor deficits of the transplanted PD rats compared to those of the control nontransplanted PD rats by decreasing the apomorphine-induced turn cycles as early as 4 weeks after transplantation. Immunofluorescence analyses showed that the differentiated DA neurons survived more than 16 weeks. Conclusions Our results showed that cells that were differentiated from NSCs had therapeutic effects in a rat PD model, which suggests that differentiated cells may be an effective treatment for patients with PD.

Objective To carry out a standard meta-analysis to determine if aspirin should be stopped before tooth extraction. Study Design The PubMed, ScienceDirect, EBSCOhost, and Science Citation Index databases were searched for studies published up to September 30, 2014. Eligible studies were restricted to randomized controlled trials (RCTs) and controlled, nonrandomized trials. Results Three RCTs and seven controlled trials met the inclusion criteria (covering 1752 patients: 529 on aspirin therapy and 1223 not on aspirin therapy). The results showed that the risk of postoperative hemorrhage was significantly higher in patients on aspirin therapy (relative risk [RR] = 2.46; 95% confidence interval [CI]: 1.45-4.81) but that bleeding time (BT) was not significantly different between the two groups (standardized mean difference [SMD] = 0.63; 95% CI: −0.04 to 1.31). Sensitivity analyses showed that the results were unstable. Conclusions We could reach a conclusion that BT is prolonged or hemorrhage is exacerbated by long-term use of aspirin. We recommend not stopping long-term aspirin use before tooth extraction but enhancing hemostasis methods, if necessary.

GNB2L1 and its O-GlcNAcylation has been reported to play roles in gastric cancer metastasis. However, the roles of GNB2L1 in chemoresistance of gastric cancer has never been determined. In the present study, we found that GNB2L1 was downregulated in chemoresistant patients of gastric cancer, and observed the decrease of GNB2L1 in protein levels instead of mRNA levels in different chemoresistant gastric cancer cell lines. Further we proved that this downregulation of GNB2L1 was resulted from its elevated O-GlcNAcylation catalyzed by OGT in both cell lines and patients. Next, we investigate the function of GNB2L1 and its O-GlcNAcylation on gastric cancer metastasis during chemoresistance, and confirmed Ser124 as the major O-GlcNAcylation site on GNB2L1 that regulated its function on metastasis. Furthermore, our data demonstrated that GNB2L1 modulated EMT via regulating the translation of EMT-related proteins in the process of chemoresistance. In summary, this study indicated that GNB2L1 and its O-GlcNAcylation regulated metastasis via modulating the translation of EMT-related proteins in the chemoresistance of gastric cancer.

Mechanical stress plays an important role in bone growth and bone remodeling. It causes stretch stress and fluid shear stress (FSS), which can be sensed by mechanosensory cells, e.g. osteocytes and osteoblasts, and further induce changes of gene expression in those cells. The FSS is thought to be the main cause in this process. However, up to now, it is still not clear what signals are triggered in the mechanosensory cells cultured in vitro and how the FSS exactly affects the expression of specific proteins. Evidences have shown that Ca2+ signaling pathway, Cyclooxygenase-prostaglandin E2 pathway, protein kinase A/protein kinase C (PKA/PKC) pathway, and drosophila mothers against decapentaplegic (Smad) protein pathway may be the key players in osteoblast differentiation by FSS. The precise mechanism involved in mechanotransduction and signal transduction remains to be elucidated. The present review gives a brief summary on the effects of these signaling pathways on the differentiation of osteoblasts cultured in vitro under FSS, to get the message of the present situation of the research on the stress transmission and signal transduction influencing osteoblast molecular activity, and to provide reference for further study on its specific mechanism.