catena-Poly[[[2-(pyridin-2-yldisulfan­yl)pyridine-κ2 N,S]copper(I)]-μ1,5-dicyanamido]

In the title compound, [Cu(C2N3)(C10H8N2S2)]n, the CuI atoms are connected by bridging dicyanamide ligands, forming chains parallel to [100]. Each CuI atom displays a tetra­hedral coordination environment, formed by one S atom and three N atoms from one 2-(pyridin-2-yldisulfan­yl)pyridine and two dicyanamide ligands. The crystal structure is stabilized by C—H⋯N hydrogen bonds, forming a three-dimensional network

Antisense oligodeoxynucleotides targeting ATM strengthen apoptosis of laryngeal squamous cell carcinoma grown in nude mice

<p>Abstract</p> <p>Background</p> <p>To conserve laryngeal function and elevate living quality of laryngeal squamous cell carcinoma (LSCC) patients, we designed antisense oligodeoxynucleotides (AS-ODNs) to reduce expression of ATM and to enhance the apoptosis of hep-2 (Human epidermoid laryngeal carcinoma) cells to radiation in vitro and in vivo.</p> <p>Methods</p> <p>The expression of ATM mRNA and protein in hep-2 cells were examined by real-time quantitative PCR and western blotting respectively. Clonogenic survival assay was carried out to detect the survival ability of hep-2 cells after irradiation, and analyzed the cell apoptosis by flow cytometry. The volume of solid tumors was measured, while TUNEL assay and western blotting used to analyze cell apoptosis and protein expression after irradiation.</p> <p>Results</p> <p>The relative ATM mRNA and protein expression in hep-2 cells treated with ATM AS-ODNs were decreased to 11.03 ± 2.51% and 48.14 ± 5.53% of that in untreated cells respectively (P <0.05). After irradiation, the survival fraction (SF) of cells treated with ATM AS-ODNs was lower than that of other groups at the same dose of radiation (P < 0.05). The inhibition rate in hep-2 cells solid tumor exposed to X-ray alone was 5.95 ± 4.52%, while it was 34.28 ± 2.43% in the group which irradiated in combination with the treatment of ATM AS-ODNs (P < 0.05). The apoptotic index for the group irradiated in combination with ATM AS-ODNs injection was 17.12 ± 4.2%, which was significantly higher than that of others (P < 0.05).</p> <p>Conclusion</p> <p>AS-ODNs of ATM reduce ATM expression and enhance hep-2 cells apoptosis to radiation in vitro and in vivo.</p

Antisense inhibition of ATM gene enhances the radiosensitivity of head and neck squamous cell carcinoma in mice

<p>Abstract</p> <p>Background</p> <p>Treatment failure after radiotherapy of head and neck squamous cell carcinoma (HNSCC) could be a significant problem. Our objective is to sensitize SCCVII cells to ionizing radiation <it>in vitro </it>and <it>in vivo </it>through inhibiting ATM expression using antisense oligodeoxynucleotides (AS-ODNs), and investigate the potential mechanism of radiosensitization.</p> <p>Methods</p> <p>We designed and synthesized AS-ODNs that target ATM mRNA to reduce the ATM expression. The influence on the expression of ATM mRNA and protein in SCCVII cells were analysed by real-time quantitative PCR and western blotting respectively. Clonogenic survival assay was performed to detect the survival ability of SCCVII cells after irradiation, while flow cytometry used to analyse the cell cycle and apoptosis. The volume of solid tumors generated with SCCVII cells was measured, and cell apoptosis was analysed by TUNEL assay after irradiation.</p> <p>Results</p> <p>The relative ATM mRNA and protein expression in SCCVII cells treated with ATM AS-ODNs were decreased to 25.7 ± 3.1% and 24.1 ± 2.8% of that in untreated cells respectively (<it>P </it>< 0.05). After irradiation, the survival fraction (SF) of cells treated with ATM AS-ODNs was lower than that of other groups at the same dose of radiation (<it>P </it>< 0.05), while the percentage of cells in G2/M phase decreased and apoptotic rate of cells increased(<it>P </it>< 0.05). The inhibition rate in SCCVII cells solid tumor exposed to X-ray alone was 23.2 ± 2.7%, while it was 56.1 ± 3.8% in the group which irradiated in combination with the treatment of ATM AS-ODNs (<it>P </it>< 0.05). The apoptotic index for the group irradiated in combination with ATM AS-ODNs injection was 19.6 ± 3.2, which was significantly higher than that of others (<it>P </it>< 0.05)</p> <p>Conclusion</p> <p>Inhibition of ATM expression sensitized SCCVII cells to ionizing radiation <it>in vitro </it>and <it>in vivo</it>. The potential mechanism should be the defective G2/M cell cycle checkpoint control and enhanced radiation-induced apoptosis.</p

Advancements and future prospects of adeno-associated virus-mediated gene therapy for sensorineural hearing loss

Sensorineural hearing loss (SNHL), a highly prevalent sensory impairment, results from a multifaceted interaction of genetic and environmental factors. As we continually gain insights into the molecular basis of auditory development and the growing compendium of deafness genes identified, research on gene therapy for SNHL has significantly deepened. Adeno-associated virus (AAV), considered a relatively secure vector for gene therapy in clinical trials, can deliver various transgenes based on gene therapy strategies such as gene replacement, gene silencing, gene editing, or gene addition to alleviate diverse types of SNHL. This review delved into the preclinical advances in AAV-based gene therapy for SNHL, spanning hereditary and acquired types. Particular focus is placed on the dual-AAV construction method and its application, the vector delivery route of mouse inner ear models (local, systemic, fetal, and cerebrospinal fluid administration), and the significant considerations in transforming from AAV-based animal model inner ear gene therapy to clinical implementation

The oxidant-antioxidant imbalance was involved in the pathogenesis of chronic rhinosinusitis with nasal polyps

BackgroundAlthough oxidative stress is involved in the pathophysiological process of chronic rhinosinusitis with nasal polyps (CRSwNP), the specific underlying mechanism is still unclear. Whether antioxidant therapy can treat CRSwNP needs further investigation.MethodsImmunohistochemistry, immunofluorescence, western blotting and quantitative polymerase chain reaction (qPCR) analyses were performed to detect the distribution and expression of oxidants and antioxidants in nasal polyp tissues. qPCR revealed correlations between oxidase, antioxidant enzymes and inflammatory cytokine levels in CRSwNP patients. Human nasal epithelial cells (HNEpCs) and primary macrophages were cultured to track the cellular origin of oxidative stress in nasal polyps(NPs) and to determine whether crocin can reduce cellular inflammation by increasing the cellular antioxidant capacity.ResultsThe expression of NOS2, NOX1, HO-1 and SOD2 was increased in nasal epithelial cells and macrophages derived from nasal polyp tissue. Oxidase levels were positively correlated with those of inflammatory cytokines (IL-5 and IL-6). Conversely, the levels of antioxidant enzymes were negatively correlated with those of IL-13 and IFN-γ. Crocin inhibited M1 and M2 macrophage polarization as well as the expression of NOS2 and NOX1 and improved the antioxidant capacity of M2 macrophages. Moreover, crocin enhanced the ability of antioxidants to reduce inflammation via the KEAP1/NRF2/HO-1 pathway in HNEpCs treated with SEB or LPS. Additionally, we observed the antioxidant and anti-inflammatory effects of crocin in nasal explants.ConclusionOxidative stress plays an important role in the development of CRSwNP by promoting various types of inflammation. The oxidative stress of nasal polyps comes from epithelial cells and macrophages. Antioxidant therapy may be a promising strategy for treating CRSwNP

Immunomodulatory effect of Bifidobacterium breve on experimental allergic rhinitis in BALB/c mice

Bifidobacterium breve (B. breve) may have a beneficial effect on allergic rhinitis (AR). The aim of the present study was to investigate whether microbial induction of regulatory T cells (Tregs) and adjustment of Th1 and Th2 responses by B. breve are associated with protection against allergic inflammation, and to identify a dose-response association in a murine AR model. Ovalbumin (OVA)-sensitized BALB/c mice were orally treated with different doses of B. breve [10(10), 10(9), 10(7) and 10(5) colony forming units (CFU)]. Following nasal challenge with OVA, sneeze frequency, serum OVA-specific immunoglobulin E (IgE) and cytokine concentrations [interleukin (IL)-4, IL-10, IL-13 and interferon-gamma], splenic percentage of cluster of differentiation (CD)4+CD25+ Tregs, and morphology of the nasal mucosa were examined. Oral treatment with live B. breve at doses of 10(7) CFU or higher alleviated nasal mucosal injury and suppressed sneezing upon repeated administration over a 6-week period. Furthermore, treatment with B. breve at these higher doses reduced the concentrations of serum OVA-specific IgE, IL-4 and IL-10, and increased the splenic percentage of CD4+CD25+ Tregs in rhinitic mice compared with those who did not receive probiotics. In contrast, treatment with B. breve at a lower dose did not indicate any effect on sneezing frequency or mucosal morphology in this animal model, even though the splenic percentage of CD4+CD25+ Tregs increased and the concentrations of serum OVA-specific IgE and IL-10 declined. B. breve exerts its anti-allergic effects by inhibiting type 2 helper T cell immune responses and enhancing CD4+CD25+ Treg activity. Sneezing was also reduced at a dose of 10(7) CFU or higher. The current study investigated the role of B. breve and aided in identifying the optimal dose of B. breve administration in the treatment of AR

Reliability and Validity of the Chinese (Mandarin) Tinnitus Handicap Inventory

ObjectivesThe Tinnitus Handicap Inventory (THI) is a commonly used self-reporting tinnitus questionnaire. We undertook this study to determine the reliability and validity of the Chinese-Mandarin version of the Tinnitus Handicap Inventory (THI-CM) for measuring tinnitus-related handicaps.MethodsWe tested the test-retest reliability, internal reliability, and construct validity of the THI-CM. Two-hundred patients seeking treatment for primary or secondary tinnitus in Southwest China were asked to complete THI-CM prior to clinical evaluation. Patients were evaluated by a clinician using standard methods, and 40 patients were asked to complete THI-CM a second time 14±3 days after the initial interview.ResultsThe test-retest reliability of THI-CM was high (Pearson correlation, 0.98), as was the internal reliability (Cronbach's α, 0.93). Factor analysis indicated that THI-CM has a unifactorial structure.ConclusionThe THI-CM version is reliable. The total score in THI-CM can be used to measure tinnitus-related handicaps in Mandarin-speaking populations

Mudskipper genomes provide insights into the terrestrial adaptation of amphibious fishes

Mudskippers are amphibious fishes that have developed morphological and physiological adaptations to match their unique lifestyles. Here we perform whole-genome sequencing of four representative mudskippers to elucidate the molecular mechanisms underlying these adaptations. We discover an expansion of innate immune system genes in the mudskippers that may provide defence against terrestrial pathogens. Several genes of the ammonia excretion pathway in the gills have experienced positive selection, suggesting their important roles in mudskippers’ tolerance to environmental ammonia. Some vision-related genes are differentially lost or mutated, illustrating genomic changes associated with aerial vision. Transcriptomic analyses of mudskippers exposed to air highlight regulatory pathways that are up- or down-regulated in response to hypoxia. The present study provides a valuable resource for understanding the molecular mechanisms underlying water-to-land transition of vertebrates