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1.
J Sci Food Agric ; 104(3): 1824-1832, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37884460

ABSTRACT

BACKGROUND: Rice taste is closely associated with endosperm composition, which varies among different rice layers. Although clarifying the relationship between this difference and nutritional taste can guide rice breeding and cultivation practices, research on this topic is limited. RESULTS: Here, typical rice varieties having excellent and poor taste characteristics were selected to analyze the distribution characteristics and differences of their components. The varieties with excellent taste exhibited lower apparent amylose content (AAC) and protein content (PC), lesser short-chain (Fa) and long-chain (Fb3 ) amylopectin (AP) and more medium-chain (Fb1+2 ) AP, higher long-to-short chain ratio (Fa:Fb3 ), and higher nitrogen (N), magnesium (Mg) and calcium (Ca) content in layer 1 (L1) than the varieties with poor taste. Layer 2 (L2) played a key role in AAC and PC regulation in the varieties with excellent taste by reducing AAC and appropriately increasing PC, consequently improving rice taste. AP structure in layer 3 (L3) substantially affected the taste of the two types of varieties. The mineral content was the highest in L1, and increased potassium (K), Ca, and Mg content improved taste in all varieties. CONCLUSION: AAC in each layer contributes to rice taste. PC and minerals primarily act on L1 and L2, whereas AP acts on L2 and L3. Therefore, the endosperm formation process should be exploited for improving rice taste. Furthermore, key resources and cultivation should be identified and regulated, respectively, to improve rice taste. © 2023 Society of Chemical Industry.


Subject(s)
Oryza , Oryza/chemistry , Taste , Plant Breeding , Amylopectin/chemistry , Endosperm/chemistry , Amylose/analysis , Minerals/analysis , Magnesium/analysis , Starch/chemistry
2.
Zhongguo Dang Dai Er Ke Za Zhi ; 26(6): 659-664, 2024 Jun 15.
Article in Zh | MEDLINE | ID: mdl-38926385

ABSTRACT

In infants with severe bronchopulmonary dysplasia (sBPD), severe pulmonary lobar emphysema may occur as a complication, contributing to significant impairment in ventilation. Clinical management of these infants is extremely challenging and some may require lobectomy to improve ventilation. However, prior to the lobectomy, it is very difficult to assess whether the remaining lung parenchyma would be able to sustain adequate ventilation postoperatively. In addition, preoperative planning and perioperative management are also quite challenging in these patients. This paper reports the utility of selective bronchial occlusion in assessing the safety and efficacy of lobectomy in a case of sBPD complicated by severe right upper lobar emphysema. Since infants with sBPD already have poor lung development and significant lung injury, lobectomy should be viewed as a non-traditional therapy and be carried out with extreme caution. Selective bronchial occlusion test can be an effective tool in assessing the risks and benefits of lobectomy in cases with sBPD and lobar emphysema. However, given the technical difficulty, successful application of this technique requires close collaboration of an experienced interdisciplinary team.


Subject(s)
Bronchopulmonary Dysplasia , Infant, Premature , Pulmonary Emphysema , Humans , Pulmonary Emphysema/surgery , Bronchopulmonary Dysplasia/etiology , Infant, Newborn , Bronchi , Male , Pneumonectomy , Female
3.
Neuroimage ; 283: 120437, 2023 Dec 01.
Article in English | MEDLINE | ID: mdl-37924896

ABSTRACT

A cortical plasticity after long-duration single side deafness (SSD) is advocated with neuroimaging evidence while little is known about the short-duration SSDs. In this case-cohort study, we recruited unilateral sudden sensorineural hearing loss (SSNHL) patients and age-, gender-matched health controls (HC), followed by comprehensive neuroimaging analyses. The primary outcome measures were temporal alterations of varied dynamic functional network connectivity (dFNC) states, neurovascular coupling (NVC) and brain region volume at different stages of SSNHL. The secondary outcome measures were pure-tone audiograms of SSNHL patients before and after treatment. A total of 38 SSNHL patients (21 [55%] male; mean [standard deviation] age, 45.05 [15.83] years) and 44 HC (28 [64%] male; mean [standard deviation] age, 43.55 [12.80] years) were enrolled. SSNHL patients were categorized into subgroups based on the time from disease onset to the initial magnetic resonance imaging scan: early- (n = 16; 1-6 days), intermediate- (n = 9; 7-13 days), and late- stage (n = 13; 14-30 days) groups. We first identified slow state transitions between varied dFNC states at early-stage SSNHL, then revealed the decreased NVC restricted to the auditory cortex at the intermediate- and late-stage SSNHL. Finally, a significantly decreased volume of the left medial superior frontal gyrus (SFGmed) was observed only in the late-stage SSNHL cohort. Furthermore, the volume of the left SFGmed is robustly correlated with both disease duration and patient prognosis. Our study offered neuroimaging evidence for the evolvement from functional to structural brain alterations of SSNHL patients with disease duration less than 1 month, which may explain, from a neuroimaging perspective, why early-stage SSNHL patients have better therapeutic responses and hearing recovery.


Subject(s)
Hearing Loss, Sensorineural , Hearing Loss, Sudden , Humans , Male , Middle Aged , Adult , Female , Cohort Studies , Hearing Loss, Sensorineural/diagnostic imaging , Hearing Loss, Sudden/diagnostic imaging , Hearing Loss, Sudden/complications , Hearing Loss, Sudden/therapy , Hearing , Neuroimaging , Retrospective Studies
4.
Bioorg Med Chem ; 90: 117383, 2023 07 15.
Article in English | MEDLINE | ID: mdl-37352577

ABSTRACT

The MUS81-EME1/2 structure-specific endonucleases play a crucial role in the processing of stalled replication forks and recombination intermediates, and have been recognized as an attractive drug target to potentiate the anti-cancer efficacy of DNA-damaging agents. Currently, no bioactive small-molecule inhibitors of MUS81 are available. Here, we performed a high-throughput small-molecule inhibitors screening, using the FRET-based DNA cleavage assay. From 7920 compounds, we identified dyngo-4a as a potent inhibitor of MUS81 complexes. Dyngo-4a effectively inhibits the endonuclease activities of both MUS81-EME1 and MUS81-EME2 complexes, with IC50 values of 0.57 µM and 2.90 µM, respectively. Surface plasmon resonance (SPR) and electrophoretic mobility shift assay (EMSA) assays reveal that dyngo-4a directly binds to MUS81 complexes (KD âˆ¼ 0.61 µM) and prevents them from binding to DNA substrates. In HeLa cells, dyngo-4a significantly suppresses bleomycin-triggered H2AX serine 139 phosphorylation (γH2AX). Together, our results demonstrate that dyngo-4a is a potent MUS81 inhibitor, which could be further developed as a potentially valuable chemical tool to explore more physiological roles of MUS81 in the cells.


Subject(s)
DNA-Binding Proteins , Endodeoxyribonucleases , Humans , Endodeoxyribonucleases/chemistry , Endodeoxyribonucleases/genetics , Endodeoxyribonucleases/metabolism , DNA-Binding Proteins/chemistry , HeLa Cells , Fluorescence Resonance Energy Transfer , High-Throughput Screening Assays , Endonucleases/metabolism , DNA Replication , DNA/metabolism
5.
Eur Arch Otorhinolaryngol ; 280(1): 167-173, 2023 Jan.
Article in English | MEDLINE | ID: mdl-35701540

ABSTRACT

PURPOSE: This study aimed to explore whether sex is influences tinnitus severity and whether the risk factors for tinnitus severity are the same in tinnitus patients of different sexes. METHODS: This was a retrospective study of data from 1427 patients complaining of tinnitus in a local hospital otolaryngology clinic from November 2019 to January 2022. All patients were interviewed and assessed by otoscopy, pure-tone audiometry, tinnitus handicap inventory (THI), visual analogue scale (VAS), and tinnitus refinement test. RESULTS: THI values were higher in females than in males (P = 0.00). Types of tinnitus sounds (OR 0.667, P = 0.000) and degree of hearing loss (OR 1.318, P = 0.000) were risk factors for tinnitus severity in males. Types of tinnitus sounds (OR 0.789, P = 0.005), sensation level (OR 1.023, P = 0.037), tinnitus types (OR 1.163, P = 0.041), tinnitus location (OR 1.198, P = 0.026), and the degree of hearing loss (OR 1.303, P = 0.000) were risk factors for tinnitus severity in females. Sex was an influencing factor for tinnitus severity. There were different risk factors for the tinnitus severity in different sexes. CONCLUSION: The risk factors for tinnitus severity differed according to sex in tinnitus patients, and the risk factors for tinnitus severity were greater in women than in men. These findings add to the literature on sex differences in tinnitus and suggest that medical and psychological screening of affected individuals and customized tinnitus treatment for each individual with tinnitus are needed. TRIAL REGISTRATION NUMBER/DATE OF REGISTRATION: ChiCTR2200057958, 2022/3/24 (retrospectively registered trials).


Subject(s)
Deafness , Hearing Loss , Tinnitus , Humans , Male , Female , Retrospective Studies , Tinnitus/diagnosis , Tinnitus/epidemiology , Tinnitus/psychology , Hearing Loss/complications , Hearing Loss/diagnosis , Hearing Loss/epidemiology , Audiometry, Pure-Tone , Sound
6.
Eur Arch Otorhinolaryngol ; 280(6): 2763-2772, 2023 Jun.
Article in English | MEDLINE | ID: mdl-36525077

ABSTRACT

PURPOSE: To explore the diagnostic auditory indicators of high noise exposure and combine them into a diagnostic model of high noise exposure and possible development of hidden hearing loss (HHL). METHODS: We recruited 101 young adult subjects and divided them according to noise exposure history into high-risk and low-risk groups. All subjects completed demographic characteristic collection (including age, noise exposure, self-reported hearing status, and headset use) and related hearing examination. RESULTS: The 8 kHz (P = 0.039) and 10 kHz (P = 0.005) distortion product otoacoustic emission amplitudes (DPOAE) (DPs) in the high-risk group were lower than those in the low-risk group. The amplitudes of the summating potential (SP) (P = 0.017) and action potential (AP) (P = 0.012) of the electrocochleography (ECochG) in the high-risk group were smaller than those in the low-risk group. The auditory brainstem response (ABR) wave III amplitude in the high-risk group was higher than that in the low-risk group. When SNR = - 7.5 dB (P = 0.030) and - 5 dB (P = 0.000), the high-risk group had a lower speech discrimination score than that of the low-risk group. The 10 kHz DPOAE DP, ABR wave III amplitude and speech discrimination score under noise with SNR = - 5 dB were combined to construct a combination diagnostic indicator. The area under the ROC curve was 0.804 (95% CI 0.713-0.876), the sensitivity was 80.39%, and the specificity was 68.00%. CONCLUSIONS: We expect that high noise exposure can be detected early with this combined diagnostic indicator to prevent HHL or sensorineural hearing loss (SNHL). TRIAL REGISTRATION NUMBER/DATE OF REGISTRATION: ChiCTR2200057989, 2022/3/25.


Subject(s)
Deafness , Hearing Loss, Noise-Induced , Hearing Loss, Sensorineural , Hearing Loss , Noise, Occupational , Young Adult , Humans , Hearing/physiology , Noise, Occupational/adverse effects , Otoacoustic Emissions, Spontaneous , Audiometry , Hearing Loss, Sensorineural/diagnosis , Evoked Potentials, Auditory, Brain Stem/physiology , Auditory Threshold , Hearing Loss, Noise-Induced/diagnosis , Hearing Loss, Noise-Induced/etiology
7.
Bioorg Med Chem ; 73: 117022, 2022 11 01.
Article in English | MEDLINE | ID: mdl-36155320

ABSTRACT

The Holliday junction (HJ) branch migrator RuvAB complex plays a fundamental role during homologous recombination and DNA damage repair, and therefore, is an attractive target for the treatment of bacterial pathogens. Pseudomonas aeruginosa (P. aeruginosa, Pa) is one of the most common clinical opportunistic bacterial pathogens, which can cause a series of life-threatening acute or chronic infections. Here, we performed a high throughput small-molecule screening targeting PaRuvAB using the FRET-based HJ branch migration assay. We identified that corilagin, bardoxolone methyl (BM) and 10-(6'-plastoquinonyl) decyltriphenylphosphonium (SKQ1) could efficiently inhibit the branch migration activity of PaRuvAB, with IC50 values of 0.40 ± 0.04 µM, 0.38 ± 0.05 µM and 4.64 ± 0.27 µM, respectively. Further biochemical and molecular docking analyses demonstrated that corilagin directly bound to PaRuvB at the ATPase domain, and thus prevented ATP hydrolysis. In contrast, BM and SKQ1 acted through blocking the interactions between PaRuvA and HJ DNA. Finally, these compounds were shown to increase the susceptibility of P. aeruginosa to UV-C irradiation. Our work, for the first time, reports the small-molecule inhibitors of RuvA and RuvB from any species, providing valuable chemical tools to dissect the functional role of each individual protein in vivo.


Subject(s)
Escherichia coli Proteins , Adenosine Triphosphate/metabolism , Bacterial Proteins/metabolism , DNA Helicases , DNA Repair , DNA, Bacterial , DNA, Cruciform/metabolism , DNA-Binding Proteins/metabolism , Escherichia coli/metabolism , Escherichia coli Proteins/metabolism , Glucosides , Hydrolyzable Tannins , Molecular Docking Simulation , Oleanolic Acid/analogs & derivatives , Pseudomonas aeruginosa/metabolism , Recombination, Genetic
8.
J Acoust Soc Am ; 144(6): EL522, 2018 Dec.
Article in English | MEDLINE | ID: mdl-30599672

ABSTRACT

Underwater operational turbine noise emitted by China's first offshore wind farm in the East China Sea Bridge of Shanghai was measured and analyzed in this study. Two sensors were used in the measurement: a hydrophone recording the underwater sound and an accelerometer placed in the turbine tower detecting the tower vibrations. Measurements were performed at two different types of wind turbines: a Sinovel 3 MW SL3000 turbine and a Shanghai Electric 3.6 MW W3600 turbine. The two turbines show similar tower vibration characteristics, characterized by a number of tonal components, mainly in the low-frequency domain (30-500 Hz). The peak vibration frequencies changed with the wind speed until the turbine approached its nominal power rating. Spectral analysis of the underwater acoustic data showed that the amplitude spectra had a strong correlation with the spectra of the turbine vibration intensity level, indicating that the measured underwater noise was generated by the tower mechanical vibration.

9.
Org Biomol Chem ; 14(9): 2774-9, 2016 Mar 07.
Article in English | MEDLINE | ID: mdl-26859743

ABSTRACT

An iodine-catalyzed reaction of 2-aminobenzamides and mucobromic acid was described and utilized to synthesize a variety of 6-oxo-5,6-dihydrodibenzo[b,h][1,6]naphthyridine-11-carboxamide derivatives in refluxing THF. As the two bromine atoms in mucobromic acid were found missing in the dibenzonaphthyridine products, a domino-type reaction mechanism involving a double elimination of hydrogen bromide was proposed.

10.
J Acoust Soc Am ; 140(3): EL242, 2016 09.
Article in English | MEDLINE | ID: mdl-27914436

ABSTRACT

Typhoon induced sediment warming has been proven important to coastal sound-field change in this study. It was observed that the temperature of the bottom waters off the coast of Qingdao increased by 5 °C after the passage of typhoon Damrey in 2012. Sediment warming due to bottom-water temperature increase was calculated and the change in sediment sound speed was estimated. Transmission loss (TL) was simulated both with and without consideration of the change in sediment sound speed induced by temperature variation and results showed TL change could be >10 dB within a distance of 16 km.

11.
Hepatology ; 60(1): 349-61, 2014 Jul.
Article in English | MEDLINE | ID: mdl-24711261

ABSTRACT

UNLABELLED: A better understanding of hepatocyte senescence could be used to treat age-dependent disease processes of the liver. Whether continuously proliferating hepatocytes could avoid or reverse senescence has not yet been fully elucidated. We confirmed that the livers of aged mice accumulated senescent and polyploid hepatocytes, which is associated with accumulation of DNA damage and activation of p53-p21 and p16(ink4a)-pRB pathways. Induction of multiple rounds continuous cell division is hard to apply in any animal model. Taking advantage of serial hepatocyte transplantation assays in the fumarylacetoacetate hydrolase-deficient (Fah(-/-)) mouse, we studied the senescence of hepatocytes that had undergone continuous cell proliferation over a long time period, up to 12 rounds of serial transplantations. We demonstrated that the continuously proliferating hepatocytes avoided senescence and always maintained a youthful state. The reactivation of telomerase in hepatocytes after serial transplantation correlated with reversal of senescence. Moreover, senescent hepatocytes harvested from aged mice became rejuvenated upon serial transplantation, with full restoration of proliferative capacity. The same findings were also true for human hepatocytes. After serial transplantation, the high initial proportion of octoploid hepatocytes decreased to match the low level of youthful liver. CONCLUSION: These findings suggest that the hepatocyte "ploidy conveyer" is regulated differently during aging and regeneration. The findings of reversal of hepatocyte senescence could enable future studies on liver aging and cell therapy.


Subject(s)
Cell Proliferation , Cellular Senescence/physiology , Hepatocytes/cytology , Hepatocytes/transplantation , Liver Regeneration/physiology , Animals , Cyclin-Dependent Kinase Inhibitor p16/metabolism , Cyclin-Dependent Kinase Inhibitor p21/metabolism , Flow Cytometry , Hepatocytes/physiology , Hydrolases/genetics , Lac Operon , Liver/cytology , Liver/physiology , Male , Mice , Mice, 129 Strain , Mice, Knockout , Polyploidy , Telomerase/metabolism , Tumor Suppressor Protein p53/metabolism
12.
Pediatr Surg Int ; 31(9): 855-8, 2015 Sep.
Article in English | MEDLINE | ID: mdl-26169529

ABSTRACT

PURPOSE: To identify age risk factors of early recurrent intussusception after pneumatic enema reduction. Management opinions are proposed. METHODS: Two thousand two hundred and ninety-five intussusception patients' medical records from January 2009 to December 2011 were retrospectively reviewed and analyzed. RESULTS: Of the 2295 patients, the intussusception of 1917 of them was initially reduced by pneumatic enema, with 127 cases recurring within 72 h. The early recurrence rate is 6.62%. The early recurrence rate of patients younger than 1 year old is 2.1% (22/1032), while the rate for those older than 1 year is 11.9% (105/885). The difference is significant (P = 0.0001). There were no significant differences between age groups older than 1 year. One hundred and seventeen cases of recurrence happened within 48 h, which accounted for 92.1% of all early recurrence. Recurrence patients were treated again with pneumatic enema, with a successful reduction in 93.7%. They were followed up for 2-4 years; the long-term recurrent rate was 11.8% (14/119). No patient had poor prognosis because of delayed treatment. CONCLUSION: Intussusception patients older than 1 year tend to have greater early recurrence rate after pneumatic enema reduction; 92.1% of the early recurrent cases happened in 48 h. There is no need to hospitalize patients after pneumatic enema reduction. A repeat pneumatic enema is a good choice before surgical approach.


Subject(s)
Enema/methods , Intussusception/therapy , Air , Child , Child, Preschool , Female , Humans , Infant , Infant, Newborn , Male , Recurrence , Risk Factors , Treatment Outcome
13.
Mol Cancer ; 13: 179, 2014 Jul 28.
Article in English | MEDLINE | ID: mdl-25070035

ABSTRACT

BACKGROUND: A safe and effective adjuvant plays an important role in the development of a vaccine. However, adjuvants licensed for administration in humans remain limited. Here, for the first time, we developed a novel combination adjuvant alum-polysaccharide-HH2 (APH) with potent immunomodulating activities, consisting of alum, polysaccharide of Escherichia coli and the synthetic cationic innate defense regulator peptide HH2. METHODS: The adjuvant effects of APH were examined using NY-ESO-1 protein-based vaccines in prophylactic and therapeutic models. We further determined the immunogenicity and anti-tumor effect of NY-ESO-1-APH (NAPH) vaccine using adoptive cellular/serum therapy in C57/B6 and nude mice. Cell-mediated and antibody-mediated immune responses were evaluated. RESULTS: The APH complex significantly promoted antigen uptake, maturation and cross-presentation of dendritic cells and enhanced the secretion of TNF-α, MCP-1 and IFN-γ by human peripheral blood mononuclear cells compared with individual components. Vaccination of NAPH resulted in significant tumor regression or delayed tumor progression in prophylactic and therapeutic models. In addition, passive serum/cellular therapy potently inhibited tumor growth of NY-ESO-1-B16. Mice treated with NAPH vaccine produced higher antibody titers and greater antibody-dependent/independent cellular cytotoxicity. Therefore, NAPH vaccination effectively stimulated innate immunity, and boosted both arms of the adaptive humoral and cellular immune responses to suppress tumorigenesis and growth of melanoma. CONCLUSIONS: Our study revealed the potential application of APH complex as a novel immunomodulatory agent for vaccines against tumor refractory and growth.


Subject(s)
Cancer Vaccines/immunology , Carcinogenesis/pathology , Melanoma/immunology , Melanoma/pathology , Polysaccharides/immunology , Animals , Antibody Specificity/drug effects , Antigens, Neoplasm/immunology , Body Weight/drug effects , Cancer Vaccines/pharmacology , Carcinogenesis/drug effects , Carcinogenesis/immunology , Cell Proliferation/drug effects , Chemokines/blood , Cross-Priming/drug effects , Dendritic Cells/drug effects , Dendritic Cells/immunology , Disease Models, Animal , Female , Humans , Immunity, Innate/drug effects , Leukocytes, Mononuclear/metabolism , Lymphocytes, Tumor-Infiltrating/drug effects , Lymphocytes, Tumor-Infiltrating/pathology , Mice, Inbred C57BL , NF-kappa B/metabolism , Polysaccharides/pharmacology , Signal Transduction/drug effects , T-Lymphocytes, Cytotoxic/drug effects , T-Lymphocytes, Cytotoxic/immunology , Tumor Burden/drug effects , Vaccination
14.
Antimicrob Agents Chemother ; 58(9): 5342-9, 2014 Sep.
Article in English | MEDLINE | ID: mdl-24982064

ABSTRACT

To design and discover new antimicrobial peptides (AMPs) with high levels of antimicrobial activity, a number of machine-learning methods and prediction methods have been developed. Here, we present a new prediction method that can identify novel AMPs that are highly similar in sequence to known peptides but offer improved antimicrobial activity along with lower host cytotoxicity. Using previously generated AMP amino acid substitution data, we developed an amino acid activity contribution matrix that contained an activity contribution value for each amino acid in each position of the model peptide. A series of AMPs were designed with this method. After evaluating the antimicrobial activities of these novel AMPs against both Gram-positive and Gram-negative bacterial strains, DP7 was chosen for further analysis. Compared to the parent peptide HH2, this novel AMP showed broad-spectrum, improved antimicrobial activity, and in a cytotoxicity assay it showed lower toxicity against human cells. The in vivo antimicrobial activity of DP7 was tested in a Staphylococcus aureus infection murine model. When inoculated and treated via intraperitoneal injection, DP7 reduced the bacterial load in the peritoneal lavage solution. Electron microscope imaging and the results indicated disruption of the S. aureus outer membrane by DP7. Our new prediction method can therefore be employed to identify AMPs possessing minor amino acid differences with improved antimicrobial activities, potentially increasing the therapeutic agents available to combat multidrug-resistant infections.


Subject(s)
Amino Acids/chemistry , Anti-Infective Agents/therapeutic use , Antimicrobial Cationic Peptides/therapeutic use , Animals , Anti-Infective Agents/adverse effects , Anti-Infective Agents/chemical synthesis , Anti-Infective Agents/pharmacology , Antimicrobial Cationic Peptides/adverse effects , Antimicrobial Cationic Peptides/chemical synthesis , Antimicrobial Cationic Peptides/pharmacology , Drug Design , Gram-Negative Bacteria/drug effects , Gram-Positive Bacteria/drug effects , Humans , Male , Mice , Mice, Inbred BALB C , Microbial Sensitivity Tests , Microscopy, Electron , Models, Biological , Staphylococcal Infections/drug therapy , Staphylococcus aureus/drug effects , Staphylococcus aureus/ultrastructure , Structure-Activity Relationship
15.
BMC Neurosci ; 15: 136, 2014 Dec 24.
Article in English | MEDLINE | ID: mdl-25539640

ABSTRACT

BACKGROUND: Noise exposure (NE) is a severe modern health hazard that induces hearing impairment. However, the noise-induced ultrastructural changes of blood-labyrinth barrier (BLB) and the potential involvements of tight junction proteins (TJP) remain inconclusive. We investigated the effects of NE on not only the ultrastructure of cochlea and permeability of BLB but also the expression of TJP within the guinea pig cochlea. RESULTS: Male albino guinea pigs were exposed to white noise for 4 h or 2 consecutive days (115 dB sound pressure level, 6 hours per day) and the hearing impairments and light microscopic change of BLB were evaluated with auditory brainstem responses (ABR) and the cochlear sensory epithelia surface preparation, respectively. The cochlear ultrastructure and BLB permeability after NE 2d were revealed with transmission electron microscope (TEM) and lanthanum nitrate-tracing techniques, respectively. The potential alterations of TJPs Claudin-5 and Occludin were quantified with immunohistochemistry and western blot. NE induced significant hearing impairment and NE 2d contributed to significant outer hair cell (OHC) loss that is most severe in the first row of outer hair cells. Furthermore, the loosen TJ and an obvious leakage of lanthanum nitrate particles beneath the basal lamina were revealed with TEM. Moreover, a dose-dependent decrease of Claudin-5 and Occludin was observed in the cochlea after NE. CONCLUSIONS: All these findings suggest that both decrease of Claudin-5 and Occludin and increased BLB permeability are involved in the pathologic process of noise-induced hearing impairment; however, the causal relationship and underlying mechanisms should be further investigated.


Subject(s)
Capillary Permeability/physiology , Claudin-5/metabolism , Cochlea/physiopathology , Cochlea/ultrastructure , Noise/adverse effects , Occludin/metabolism , Animals , Blotting, Western , Epithelium/physiopathology , Evoked Potentials, Auditory, Brain Stem , Guinea Pigs , Hearing Loss, Noise-Induced/pathology , Hearing Loss, Noise-Induced/physiopathology , Immunohistochemistry , Lanthanum , Male , Microscopy, Electron, Transmission , Random Allocation
16.
Int J Med Sci ; 11(9): 870-9, 2014.
Article in English | MEDLINE | ID: mdl-25013366

ABSTRACT

MSCs-based therapy for cancer is a relatively new but rapidly growing area of research. Human term placenta, an attractive source of MSCs (PMSCs), appears to have great advantage due to its easy access without invasive procedures, its lack of ethical issues and its high-throughput and young age. In the present study, we isolated MSCs from placenta and characterized their morphology and differentiation capacities. We next investigated the underlying antitumor effects and the potential mechanism of PMSCs to express endostatin using adenoviral transduction (Ad-Endo) in a colorectal peritoneal carcinomatosis (CRPC) mouse model. For in vitro experiments, the migratory potential of Ad-Endo-PMSCs towards tumor cells was demonstrated using a double-chamber assay, and the anti-angiogenesis ability of endostatin from engineered PMSCs was evaluated using the tube formation assay. For the in vivo study, mice harboring CT26 colorectal cancer indicated a significant reduction in tumor nodules and a prolongation of survival following Ad-Endo-PMSCs therapy. These observations were associated with significantly decreased tumor cell proliferation and blood vessel counts as well as increased tumor cell apoptosis. These data suggested the potential of PMSCs-based gene therapy for the targeted delivery of therapeutic proteins in cancer.


Subject(s)
Carcinogenesis/genetics , Colorectal Neoplasms/genetics , Endostatins/biosynthesis , Peritoneum/pathology , Adenoviridae , Animals , Colorectal Neoplasms/pathology , Female , Gene Expression Regulation, Neoplastic , Genetic Therapy , Humans , Mesenchymal Stem Cells/cytology , Mesenchymal Stem Cells/metabolism , Mice , Placenta/cytology , Pregnancy
17.
Sci Rep ; 14(1): 16741, 2024 07 20.
Article in English | MEDLINE | ID: mdl-39033211

ABSTRACT

Diabetes retinopathy (DR) is a critical clinical disease with that causes irreversible visual damage in adults, and may even lead to permanent blindness in serious cases. Early identification and treatment of DR is critical. Our aim was to train and externally validate a prediction nomogram for early prediction of DR. 2381 patients with type 2 diabetes mellitus (T2DM) were retrospective study from the First Affiliated Hospital of Xinjiang Medical University in Xinjiang, China, hospitalised between Jan 1, 2019 and Jun 30, 2022. 962 patients with T2DM from the Suzhou BenQ Hospital in Jiangsu, China hospitalised between Jul 1, 2020 to Jun 30, 2022 were considered for external validation. The least absolute shrinkage and selection operator (LASSO) and multivariate logistic regression was performed to identify independent predictors and establish a nomogram to predict the occurrence of DR. The performance of the nomogram was evaluated using a receiver operating characteristic curve (ROC), a calibration curve, and decision curve analysis (DCA). Neutrophil, 25-hydroxyvitamin D3 [25(OH)D3], Duration of T2DM, hemoglobin A1c (HbA1c), and Apolipoprotein A1 (ApoA1) were used to establish a nomogram model for predicting the risk of DR. In the development and external validation groups, the areas under the curve of the nomogram constructed from the above five factors were 0.834 (95%CI 0.820-0.849) and 0.851 (95%CI 0.829-0.874), respectively. The nomogram demonstrated excellent performance in the calibration curve and DCA. This research has developed and externally verified that the nomograph model shows a good predictive ability in assessing DR risk in people with type 2 diabetes. The application of this model will help clinicians to intervene early, thus effectively reducing the incidence rate and mortality of DR in the future, and has far-reaching significance in improving the long-term health prognosis of diabetes patients.


Subject(s)
Diabetes Mellitus, Type 2 , Diabetic Retinopathy , Nomograms , Humans , Diabetes Mellitus, Type 2/complications , Diabetic Retinopathy/diagnosis , Male , Female , Middle Aged , Retrospective Studies , Aged , ROC Curve , Risk Factors , China/epidemiology
18.
Zhongguo Gu Shang ; 37(6): 5605-4, 2024 Jun 25.
Article in Zh | MEDLINE | ID: mdl-38910377

ABSTRACT

OBJECTIVE: To explore preemptive analgesic effect of preoperative intramural tramadol injection in percutaneous kyphoplasty (PKP) of vertebrae following local anesthesia. METHODS: From August 2019 to June 2021, 118 patients with thoraco lumbar osteoporotic fractures were treated and divided into observation group and control group, with 59 patients in each gruop. In observation group, there were 26 males and 33 females, aged from 57 to 80 years old with an average of (67.69±4.75)years old;14 patients on T11, 12 patients on T12, 18 patients on L1, 15 patients on L2;tramadol with 100 mg was injected intramuscularly half an hour before surgery in observation group. In control group, there were 24 males and 35 females, aged from 55 to 77 years old with an average of (68.00±4.43) years old;19 patients on T11, 11 patients on T12, 17patients on L1, 12 patients on L2;the same amount of normal saline was injected intramuscularly in control group. Observation indicators included operation time, intraoperative bleeding, visual analogue scale (VAS) evaluation and recording of preoperative (T0), intraoperative puncture(T1), and working cannula placement (T2) between two groups of patients, at the time of balloon dilation (T3), when the bone cement was injected into the vertebral body (T4), 2 hours after the operation (T5), and the pain degree at the time of discharge(T6);adverse reactions such as dizziness, nausea and vomiting were observed and recorded;the record the patient's acceptance of repeat PKP surgery. RESULTS: All patients were successfully completed PKP via bilateral pedicle approach, and no intravenous sedative and analgesic drugs were used during the operation. There was no significant difference in preoperative general data and VAS(T0) between two groups (P>0.05). There was no significant difference in operation time and intraoperative blood loss between the two groups (P>0.05). VAS of T1, T2, T3, T4 and T5 in observation group were all lower than those in control group(P<0.05), and there was no significant difference in T6 VAS (P>0.05). T6 VAS between two groups were significantly lower than those of T0, and the difference was statistically significant (P<0.05). There was no significant difference in incidence of total adverse reactions between two groups (P>0.05). There was a statistically significant difference in the acceptance of repeat PKP surgery (P<0.05). CONCLUSION: Half an hour before operation, intramuscular injection of tramadol has a clear preemptive analgesic effect for PKP of single-segment thoracolumbar osteoporotic fracture vertebral body under local anesthesia, which could increase the comfort of patients during operation and 2 hours after operation, and improve patients satisfaction with surgery.


Subject(s)
Anesthesia, Local , Kyphoplasty , Lumbar Vertebrae , Osteoporotic Fractures , Thoracic Vertebrae , Tramadol , Humans , Female , Male , Aged , Tramadol/administration & dosage , Middle Aged , Kyphoplasty/methods , Thoracic Vertebrae/surgery , Thoracic Vertebrae/injuries , Osteoporotic Fractures/surgery , Lumbar Vertebrae/surgery , Anesthesia, Local/methods , Aged, 80 and over , Analgesia/methods , Pain, Postoperative/drug therapy , Pain, Postoperative/prevention & control , Spinal Fractures/surgery , Analgesics, Opioid/administration & dosage
19.
Huan Jing Ke Xue ; 45(3): 1233-1242, 2024 Mar 08.
Article in Zh | MEDLINE | ID: mdl-38471840

ABSTRACT

Promoting regions with favorable conditions to take the lead in reaching a carbon peak is an inevitable step towards achieving the dual carbon goals under the "nationwide coordinated action" plan. Considering the differences among Chinese provinces, this study measured the peaking pressure of each province based on the spatial distribution of carbon emissions. We then constructed a provincial peaking capacity evaluation system based on five dimensions, namely, peaking pressure, emission reduction status, economic development, policy support, and resource endowment, to comprehensively evaluate the carbon peaking capacity of 30 provincial administrative regions in China, excluding Hong Kong, Macau, Taiwan, and Tibet, using the entropy value method to determine the index weights. The 30 provinces were divided into five peaking tiers according to the evaluation results. The results showed that:① 18 regions, such as Hainan and Beijing, displayed a surplus in carbon emission space; eight regions, including Hebei and Shandong, showed a deficit in carbon emission space; and the carbon emission spaces allocated to Zhejiang, Anhui, Henan, and Hubei were comparable to their respective actual emissions. ② Developed regions generally had a higher carbon peaking capacity than that of less developed regions, with Beijing and Shanghai showing outstanding carbon peaking capacity, whereas Jiangxi and Guizhou had more room to improve their capacity. Finally, differentiated peaking targets and priority actions were proposed according to the provinces' different peaking tiers and local conditions.

20.
Biochim Biophys Acta Mol Basis Dis ; 1870(3): 167024, 2024 03.
Article in English | MEDLINE | ID: mdl-38242180

ABSTRACT

Oxidative stress is the common mechanism of sensorineural hearing loss (SNHL) caused by many factors, such as noise, drugs and ageing. Here, we used tert-butyl hydroperoxide (t-BHP) to cause oxidative stress damage in HEI-OC1 cells and in an in vitro cochlear explant model. We observed lipid peroxidation, iron accumulation, mitochondrial shrinkage and vanishing of mitochondrial cristae, which caused hair cell ferroptosis, after t-BHP exposure. Moreover, the number of TUNEL-positive cells in cochlear explants and HEI-OC1 cells increased significantly, suggesting that t-BHP caused the apoptosis of hair cells. Administration of deferoxamine (DFOM) significantly attenuated t-BHP-induced hair cell loss and disordered hair cell arrangement in cochlear explants as well as HEI-OC1 cell death, including via apoptosis and ferroptosis. Mechanistically, we found that DFOM treatment reduced t-BHP-induced lipid peroxidation, iron accumulation and mitochondrial pathological changes in hair cells, consequently mitigating apoptosis and ferroptosis. Moreover, DFOM treatment alleviated GSH depletion caused by t-BHP and activated the Nrf2 signalling pathway to exert a protective effect. Furthermore, we confirmed that the protective effect of DFOM mainly depended on its ability to chelate iron by constructing Fth1 knockout (KO), TfR1 KO and Nrf2 KO HEI-OC1 cell lines using CRISPR/Cas9 technology and a Flag-Fth1 (overexpression) HEI-OC1 cell line using the FlpIn™ System. Our findings suggest that DFOM is a potential drug for SNHL treatment due to its ability to inhibit apoptosis and ferroptosis by chelating iron and scavenging reactive oxygen species (ROS).


Subject(s)
Deferoxamine , Ototoxicity , Humans , tert-Butylhydroperoxide/toxicity , tert-Butylhydroperoxide/metabolism , Deferoxamine/pharmacology , Ototoxicity/metabolism , NF-E2-Related Factor 2/genetics , NF-E2-Related Factor 2/metabolism , Hair Cells, Auditory/metabolism , Iron/metabolism
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