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2.
Ultrason Sonochem ; 108: 106978, 2024 Jul 03.
Article in English | MEDLINE | ID: mdl-38971086

ABSTRACT

Drying, as a critical step in the production of air-dried beef, has a direct impact on the quality of the final product. Innovatively, a composite system incorporating contact ultrasound (CU) and infrared radiation (IR) as auxiliary measures within a hot air drying (HAD) framework was built in this research, and the effects of these techniques on the drying kinetics, protein denaturation, and moisture transformation of air-dried beef were investigated. In comparison to HAD treatment, the integrated CU and IR (CU-IRD) system displayed marked enhancements in heat and moisture transport efficiency, thereby saving 36.84% of time expenditure and contributing favorably to the improved moisture distribution of the end-product. This was mainly ascribed to the denaturation of myosin induced by IR thermal effect and the micro-channel produced by CU sponge effect, thus increasing T2 relaxation time and the proportion of free water. In conclusion, the composite system solved the problem of surface hardening and reduces hardness and chewiness of air-dried beef by 40.42% and 45.25% respectively, but inevitably increased the energy burden by 41.60%.

3.
Genes (Basel) ; 15(6)2024 May 23.
Article in English | MEDLINE | ID: mdl-38927601

ABSTRACT

Apomixis is a common reproductive characteristic of Zanthoxylum plants, and RWP-RKs are plant-specific transcription factors known to regulate embryonic development. However, the genome-wide analysis and function prediction of RWP-RK family genes in Z. armatum are unclear. In this study, 36 ZaRWP-RK transcription factors were identified in the genome of Z. armatum, among which 15 genes belonged to the RKD subfamily and 21 belonged to the NLP subfamily. Duplication events of ZaRWP-RK genes were mainly segmental duplication, and synteny analysis revealed a close phylogenetic relationship between Z. armatum and Arabidopsis. The analysis of cis-elements indicated that ZaRWP-RK genes may be involved in the regulation of the embryonic development of Z. armatum by responding to plant hormones such as abscisic acid, auxin, and gibberellin. Results of a real-time PCR showed that the expression levels of most ZaRWP-RK genes were significantly increased from flowers to young fruits. Protein-protein interaction network analysis further revealed the potential roles of the ZaRWP-RK proteins in apomixis. Collectively, this study is expected to improve our understanding of ZaRWP-RK transcription factors and provide a theoretical basis for future investigations into the ZaRWP-RK genes and their regulatory mechanisms in the apomixis process of Z. armatum.


Subject(s)
Gene Expression Regulation, Plant , Phylogeny , Plant Proteins , Transcription Factors , Zanthoxylum , Zanthoxylum/genetics , Zanthoxylum/metabolism , Plant Proteins/genetics , Plant Proteins/metabolism , Transcription Factors/genetics , Transcription Factors/metabolism , Genome, Plant , Plant Growth Regulators/metabolism , Plant Growth Regulators/genetics , Apomixis/genetics , Arabidopsis/genetics
4.
Fish Shellfish Immunol ; 151: 109701, 2024 Jun 13.
Article in English | MEDLINE | ID: mdl-38878911

ABSTRACT

In the field of aquaculture, the enhancement of animal health and disease prevention is progressively being tackled using alternatives to antibiotics, including vaccines and probiotics. This study was designed to evaluate the potential of a recombinant Bacillus methylotrophicus, engineered to express the outer membrane channel protein TolC of Aeromonas hydrophila AH3 and the green fluorescent protein GFP, as an oral vaccine. Initially, the genes encoding tolC and GFP were cloned into a prokaryotic expression system, and anti-TolC mouse antiserum was generated. Subsequently, the tolC gene was subcloned into a modified pMDGFP plasmid, which was transformed into B. methylotrophicus WM-1 for protein expression. The recombinant B. methylotrophicus BmT was then administered to grass carp via co-feeding, and its efficacy as an oral vaccine was assessed. Our findings demonstrated successful expression of the 55 kDa TolC and 28 kDa GFP proteins, and the preparation of polyclonal antibodies with high specificity. The BmT exhibited stable expression of the GFP-TolC fusion protein and excellent genetic stability. Following oral immunization, significant elevations were observed in serum-specific IgM levels and the activities of acid phosphatase (ACP), alkaline phosphatase (AKP), superoxide dismutase (SOD), and lysozyme (LZM) in grass carp. Concurrently, significant upregulation of immune-related genes, including IFN-I, IL-10, IL-1ß, TNF-α, and IgT, was noted in the intestines, head kidney, and spleen of the grass carp. Colonization tests further revealed that the BmT persisted in the gut of immunized fish even after a fasting period of 7 days. Notably, oral administration of BmT enhanced the survival rate of grass carp following A. hydrophila infection. These results suggest that the oral BmT vaccine developed in this study holds promise for future applications in aquaculture.

5.
Biochem Biophys Res Commun ; 722: 150132, 2024 Aug 30.
Article in English | MEDLINE | ID: mdl-38788354

ABSTRACT

OBJECTIVE: The present study aims to investigate the protective potential of salidroside in both lung ischemia/reperfusion injury (LIRI) mice model and cell hypoxia/reoxygenation (H/R)model and the involvement of ferroptosis and JAK2/STAT3 pathway. MATERIALS AND METHODS: After we established the IR-induced lung injury model in mice, we administered salidroside and the ferroptosis inhibitor, ferrostatin-1, then assessed the lung tissue injury, ferroptosis (levels of reactive oxygen species level, malondialdehyde and glutathione), and inflammation in lung tissues. The levels of ferroptosis-related proteins (glutathione peroxidase 4, fibroblast-specific protein 1, solute carrier family 1 member 5 and glutaminase 2) in the lung tissue were measured with Western blotting. Next, BEAS-2B cells were used to establish an H/R cell model and treated with salidroside or ferrostatin-1 before the cell viability and the levels of lactate dehydrogenase (LDH), inflammatory factor, ferroptosis-related proteins were measured. The activation of the JAK2/STAT3 signaling pathway was measured with Western blotting, then its role was confirmed with STAT3 knockdown. RESULTS: Remarkably, salidroside was found to alleviate ferroptosis, inflammation, and lung injury in LIRI mice and the cell injury in H/R cell model. Severe ferroptosis were observed in LIRI mice models and H/R-induced BEAS-2B cells, which was alleviated by salidroside. Furthermore, salidroside could inhibit JAK2/STAT3 activation induced by LIRI. STAT3 knockdown could enhance the effect of salidroside treatment on H/R-induced cell damage and ferroptosis in vitro. CONCLUSIONS: Salidroside inhibits ferroptosis to alleviate lung ischemia reperfusion injury via the JAK2/STAT3 signaling pathway.


Subject(s)
Ferroptosis , Glucosides , Janus Kinase 2 , Phenols , Reperfusion Injury , STAT3 Transcription Factor , Signal Transduction , Phenols/pharmacology , Phenols/therapeutic use , Animals , Ferroptosis/drug effects , Janus Kinase 2/metabolism , Glucosides/pharmacology , STAT3 Transcription Factor/metabolism , Reperfusion Injury/drug therapy , Reperfusion Injury/metabolism , Reperfusion Injury/pathology , Signal Transduction/drug effects , Male , Mice , Humans , Mice, Inbred C57BL , Lung/pathology , Lung/drug effects , Lung/metabolism , Cell Line , Lung Injury/drug therapy , Lung Injury/metabolism , Lung Injury/pathology , Lung Injury/etiology
6.
Medicine (Baltimore) ; 103(16): e37662, 2024 Apr 19.
Article in English | MEDLINE | ID: mdl-38640318

ABSTRACT

BACKGROUND: Thoracic surgery without general anesthesia can be traced back to the First World War, and thoracic epidural block was used to complete the operation due to a large number of patients with gunshot wounds who needed emergency thoracic surgery. By reducing the intraoperative opioid dose, intraoperative and postoperative opioid-related adverse events such as respiratory depression, nausea and vomiting, delirium, hyperalgesia, and other side effects can be reduced to the benefit of patients. METHODS: A 72-year-old male patient was admitted to the hospital with a 5-day history of multifocal pain throughout the body caused by a fall. The injury was not treated at that time, and the pain gradually increased, accompanied by cough with difficulty expelling sputum. DIAGNOSES: Left lung contusion; traumatic pneumonia; multiple left rib fractures; left fluid pneumothorax; thyroid tumor of unknown nature, possibly malignant. Grade I tracheal stenosis; Sequelae of cerebral infarction. Because of goiter and severe tracheal compression, the patient was not intubated and received deopiated general anesthesia combined with epidural anesthesia to preserve spontaneous breathing. OUTCOMES: At the end of the video-assisted thoracoscopic exploration, the patient was immediately conscious and returned directly to the ward 6 min later. The patient was able to move freely after surgery and eat normally within 6 h of surgery. The postoperative visual analog scale score was 2 points, and there were no anesthetic complications during the follow-up. CONCLUSION: The opioid-free anesthesia strategy of tubeless general anesthesia, allowing spontaneous breathing combined with epidural anesthesia in elderly patients with tracheal stenosis undergoing video-assisted thoracoscopic surgery can not only avoid accidents and injuries caused by tracheal intubation and mechanical ventilation, but can also significantly reduce postoperative respiratory complications, optimize postoperative analgesia, and help achieve enhanced recovery after surgery.


Subject(s)
Anesthesia, Epidural , Tracheal Stenosis , Wounds, Gunshot , Male , Humans , Aged , Thoracic Surgery, Video-Assisted , Analgesics, Opioid , Constriction, Pathologic , Pain, Postoperative/drug therapy , Postoperative Complications/etiology
7.
J Proteome Res ; 23(5): 1559-1570, 2024 May 03.
Article in English | MEDLINE | ID: mdl-38603467

ABSTRACT

The ongoing evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to the emergence of different variants of concerns with immune evasion that have been prevalent over the past three years. Nanobodies, the functional variable regions of camelid heavy-chain-only antibodies, have garnered interest in developing neutralizing antibodies due to their smaller size, structural stability, ease of production, high affinity, and low immunogenicity, among other characteristics. In this work, we describe an integrated proteomics platform for the high-throughput screening of nanobodies against different SARS-CoV-2 spike variants. To demonstrate this platform, we immunized a camel with subunit 1 (S1) of the wild-type spike protein and constructed a nanobody phage library. The binding and neutralizing activities of the nanobodies against 72 spike variants were then measured, resulting in the identification of two nanobodies (C-282 and C-39) with broad neutralizing activity against six non-Omicron variants (D614G, Alpha, Beta, Gamma, Delta, Kappa) and five Omicron variants (BA.1-5). Their neutralizing capability was validated using in vitro pseudovirus-based neutralization assays. All these results demonstrate the utility of our proteomics platform to identify new nanobodies with broad neutralizing capability and to develop a treatment for patients with SARS-CoV-2 variant infection in the future.


Subject(s)
Antibodies, Neutralizing , Antibodies, Viral , COVID-19 , Camelus , Proteomics , SARS-CoV-2 , Single-Domain Antibodies , Spike Glycoprotein, Coronavirus , SARS-CoV-2/immunology , Antibodies, Neutralizing/immunology , Single-Domain Antibodies/immunology , Single-Domain Antibodies/chemistry , Proteomics/methods , Spike Glycoprotein, Coronavirus/immunology , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/genetics , Animals , Humans , COVID-19/immunology , COVID-19/virology , Antibodies, Viral/immunology , Neutralization Tests
8.
Aesthetic Plast Surg ; 48(11): 2034-2041, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38676769

ABSTRACT

BACKGROUND: As a rare auricular deformity, despite numerous surgical procedures for correcting moderate-to-severe question mark ears described in past studies, there remains a need to explore a more cost-effective approach. The optimal utilization of ear cartilage and surrounding skin while achieving superior outcomes continues to pose a significant challenge. METHODS: From 2018 to 2023, twenty-four patients with unilateral question mark ear were enrolled in this study. Seven of them were severe type deformities (absence of lower part of auricle), and seventeen were moderate (only cleft between helix and lobule). All patients were treated with new method using local cartilage and flap without damage in unaffected area. RESULTS: All patients were satisfied with significant improvement of question mark ear and the overall symmetrical appearance. The surgical scar was not obvious. No complications were observed. The follow-up period revealed that the corrective procedure kept producing the symmetrical and cosmetic results. CONCLUSION: Our new method enables optimal utilization of deformed tissue and surrounding skin, rendering this method effective and reliable for correcting moderate-to-severe question mark ears. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .


Subject(s)
Ear Cartilage , Esthetics , Plastic Surgery Procedures , Surgical Flaps , Humans , Female , Surgical Flaps/transplantation , Male , Ear Cartilage/surgery , Ear Cartilage/transplantation , Plastic Surgery Procedures/methods , Young Adult , Adult , Adolescent , Treatment Outcome , Retrospective Studies , Cohort Studies , Follow-Up Studies , Patient Satisfaction/statistics & numerical data , Child , Risk Assessment , Ear, External/surgery , Ear, External/abnormalities , Ear Auricle/surgery , Ear Auricle/abnormalities
9.
J Plast Reconstr Aesthet Surg ; 92: 237-243, 2024 May.
Article in English | MEDLINE | ID: mdl-38574570

ABSTRACT

BACKGROUND: The presence of polyotia in individuals with microtia is a rare deformity. Due to the intricate structure of the auricle, uncertain etiology, and challenging corrective techniques, it has always been a focal point in the field of plastic surgery. The present study presents a technique for correcting the combination of polyotia and microtia by utilizing residual ear tissue as graft material. METHODS: The retrospective study included 23 patients with polyotia and microtia from 2018 to 2022. The residual ear tissue was used to rectify auricular deformities in all patients. The patients were instructed to evaluate the satisfaction of the auricle shape using a visual analog scale (VAS) both before and 6 months after the surgical procedure. The esthetic outcomes of auricle subunits were simultaneously assessed by a senior physician pre- and postoperatively. RESULTS: The mean duration of follow-up in this study was 8.73 months. The preoperative VAS satisfaction score was recorded as 2.26 ± 0.86, while the post-operative VAS score significantly increased to 7.86 ± 0.86. The preoperative auricle esthetic outcomes score was recorded as 9.95 ± 1.74, while the post-operative score significantly increased to 24.04 ± 2.16. The follow-up period did not present any cases of flap necrosis, hematoma, infection, or wound dehiscence. CONCLUSION: The study demonstrates that comprehensive utilization of residual auricular tissue can lead to optimal outcomes in correcting polyotia with concha-type microtia. The utilization of residual ear tissue can be maximized to streamline the operation, minimize bodily harm, and enhance patient satisfaction.


Subject(s)
Congenital Microtia , Ear Auricle , Plastic Surgery Procedures , Humans , Congenital Microtia/surgery , Male , Retrospective Studies , Female , Plastic Surgery Procedures/methods , Child , Adolescent , Ear Auricle/surgery , Ear Auricle/abnormalities , Patient Satisfaction , Esthetics , Young Adult , Adult , Ear, External/surgery , Ear, External/abnormalities
10.
Cancer Immunol Immunother ; 73(3): 47, 2024 Feb 13.
Article in English | MEDLINE | ID: mdl-38349411

ABSTRACT

The response rate of anti-PD1 therapy is limited, and the influence of anti-PD1 therapy on cancer patients is unclear. To address these challenges, we conducted a longitudinal analysis of plasma proteomic changes with anti-PD1 therapy in non-small cell lung cancer (NSCLC), alveolar soft part sarcoma (ASPS), and lymphoma patients. We included 339 plasma samples before and after anti-PD1 therapy from 193 patients with NSCLC, ASPS, or lymphoma. The plasma proteins were detected using data-independent acquisition-mass spectrometry and customable antibody microarrays. Differential proteomic characteristics in responders (R) and non-responders (NR) before and after anti-PD1 therapy were elucidated. A total of 1019 proteins were detected using our in-depth proteomics platform and distributed across 10-12 orders of abundance. By comparing the differential plasma proteome expression between R and NR groups, 50, 206, and 268 proteins were identified in NSCLC, ASPS, and lymphoma patients, respectively. Th17, IL-17, and JAK-STAT signal pathways were identified upregulated in NR group, while cellular senescence and transcriptional misregulation pathways were activated in R group. Longitudinal proteomics analysis revealed the IL-17 signaling pathway was downregulated after treatment. Consistently, many proteins were identified as potential combinatorial therapeutic targets (e.g., IL-17A and CD22). Five noninvasive biomarkers (FLT4, SFTPB, GNPTG, F5, and IL-17A) were further validated in an independent lymphoma cohort (n = 39), and another three noninvasive biomarkers (KIT, CCL3, and TNFSF1) were validated in NSCLC cohort (n = 76). Our results provide molecular insights into the anti-PD1 therapy in cancer patients and identify new therapeutic strategies for anti-PD1-resistant patients.


Subject(s)
Anti-Infective Agents , Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Lymphoma , Humans , Interleukin-17 , Carcinoma, Non-Small-Cell Lung/drug therapy , Proteomics , Lung Neoplasms/drug therapy , Penicillins , Biomarkers , Transferases (Other Substituted Phosphate Groups)
11.
Mol Cell Proteomics ; 23(3): 100729, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38309569

ABSTRACT

Diagnosing, predicting disease outcome, and identifying effective treatment targets for virus-related cancers are lacking. Protein biomarkers have the potential to bridge the gap between prevention and treatment for these types of cancers. While it has been shown that certain antibodies against EBV proteins could be used to detect nasopharyngeal carcinoma (NPC), antibodies targeting are solely a tiny part of the about 80 proteins expressed by the EBV genome. Furthermore, it remains unclear what role other viruses play in NPC since many diseases are the result of multiple viral infections. For the first time, this study measured both IgA and IgG antibody responses against 646 viral proteins from 23 viruses in patients with NPC and control subjects using nucleic acid programmable protein arrays. Candidate seromarkers were then validated by ELISA using 1665 serum samples from three clinical cohorts. We demonstrated that the levels of five candidate seromarkers (EBV-BLLF3-IgA, EBV-BLRF2-IgA, EBV-BLRF2-IgG, EBV-BDLF1-IgA, EBV-BDLF1-IgG) in NPC patients were significantly elevated than controls. Additional examination revealed that NPC could be successfully diagnosed by combining the clinical biomarker EBNA1-IgA with the five anti-EBV antibodies. The sensitivity of the six-antibody signature at 95% specificity to diagnose NPC was comparable to the current clinically-approved biomarker combination, VCA-IgA, and EBNA1-IgA. However, the recombinant antigens of the five antibodies are easier to produce and standardize compared to the native viral VCA proteins. This suggests the potential replacement of the traditional VCA-IgA assay with the 5-antibodies combination to screen and diagnose NPC. Additionally, we investigated the prognostic significance of these seromarkers titers in NPC. We showed that NPC patients with elevated BLLF3-IgA and BDLF1-IgA titers in their serum exhibited significantly poorer disease-free survival, suggesting the potential of these two seromarkers as prognostic indicators of NPC. These findings will help develop serological tests to detect and treat NPC in the future.


Subject(s)
Nasopharyngeal Neoplasms , Proteome , Humans , Nasopharyngeal Carcinoma/diagnosis , Nasopharyngeal Neoplasms/diagnosis , Herpesvirus 4, Human/genetics , Capsid Proteins , Antigens, Viral , Biomarkers , Immunoglobulin G , Immunoglobulin A
12.
Aesthetic Plast Surg ; 48(9): 1679-1687, 2024 May.
Article in English | MEDLINE | ID: mdl-38379008

ABSTRACT

OBJECTIVES: Recently, radial cartilage incision (first-stage) at an early age combined with free auricular composite tissue grafting (second-stage) can effectively correct the concha-type microtia with the moderate or severe folded cartilage in the middle and upper third auricle, but radial cartilage incision's effects on the growth of the ear remain to be determined. The authors aimed to evaluate the effects of radial cartilage incision in young rabbits model. METHODS: Ten New Zealand white rabbits were included in our experiment. Two ears of each rabbit were divided randomly into two groups. The experimental group was operated with radial cartilage incision, and no intervention was given to the control group. The ear width, length, and perimeter were noted every two weeks. Auricular surface area was noted at 4 and 22 weeks old. The repeated measures ANOVA was used to describe ears' growth trend. A paired-sample's t test is conducted to test whether there are significant differences among the variables through the SPSS25.0 software. RESULTS: The growth tendencies of the ear length, width, and perimeter were observed and analyzed. The growth curves of the experimental ears were similar to that of the control. There was no significant difference in the increased ratio of surface area among the two groups. The cartilage of the experimental ears showed no change in biomechanical properties compared to that of control group. CONCLUSION: This study shows that radial cartilage incision at an early age does not influence the growth of rabbit ear length, width, perimeter, and surface area and also does not change the biomechanical properties of the cartilage. LEVEL OF EVIDENCE I: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors   www.springer.com/00266 .


Subject(s)
Ear Cartilage , Animals , Rabbits , Ear Cartilage/surgery , Random Allocation , Ear, External/surgery , Congenital Microtia/surgery , Plastic Surgery Procedures/methods , Female , Disease Models, Animal
13.
Heart Lung ; 64: 24-30, 2024.
Article in English | MEDLINE | ID: mdl-37984100

ABSTRACT

BACKGROUND: Thrombocytopenia is a common disorder during influenza that is related to high mortality. OBJECTIVES: A prospective study was performed to investigate the association of immunoglobulin subclass changes accompanying incident thrombocytopenia with clinical outcomes in patients with severe influenza. METHODS: 96 influenza patients were recruited and divided into two groups, patients with thrombocytopenia (n = 30) and patients without thrombocytopenia (n = 66). Plasma microarrays were used for quantitative analysis of immunoglobulins. The endpoint was 28-day mortality. Continuous platelet count, d-dimer, level of each Ig subclass and other variables were compared between the two groups. Kaplan-Meier curve was taken to analyze the 28-day survival rate of the two groups and Cox regression analysis was performed to identify variables independently associated with 28-day mortality. RESULTS: Patients with thrombocytopenia had significantly high values of d-dimer at admission and when platelet lowest with high SOFA score. Their IgA2, IgG2, and IgG4 values were also lower than those without thrombocytopenia. Patients without thrombocytopenia had a higher 28-day survival rate than those in the thrombocytopenia group. In the multivariate Cox regression model, age (HR = 1.036, 95%CI = 1.011-1.062), IgG2 (HR = 0.990, 95%CI = 0.982-0.998), platelet minimum within 28 days (HR = 0.991, 95%CI = 0.982-0.999) and d-dimer when platelet lowest (HR = 1.091, 95%CI = 1.047-1.137) were independently related to 28-day mortality. CONCLUSION: Decreased IgG2 may be associated with thrombocytopenia. A coexistence of thrombocytopenia, IgG2 reduction and d-dimer elevation may improve the accuracy of mortality prediction in patients with influenza pneumonia.


Subject(s)
Influenza, Human , Pneumonia , Thrombocytopenia , Humans , Immunoglobulin G , Influenza, Human/complications , Prospective Studies , Thrombocytopenia/complications , Retrospective Studies
14.
Eur J Med Res ; 28(1): 570, 2023 Dec 06.
Article in English | MEDLINE | ID: mdl-38053192

ABSTRACT

BACKGROUND: Alzheimer's disease (AD) and Parkinson's disease (PD), two common irreversible neurodegenerative diseases, share similar early stage syndromes, such as olfaction dysfunction. Yet, the potential comorbidity mechanism of AD and PD was not fully elucidated. METHODS: The gene expression profiles of GSE5281 and GSE8397 were downloaded from the Gene Expression Omnibus (GEO) database. We utilized a series of bioinformatics analyses to screen the overlapped differentially expressed genes (DEGs). The hub genes were further identified by the plugin CytoHubba of Cytoscape and validated in the hippocampus (HIP) samples of APP/PS-1 transgenic mice and the substantial nigra (SN) samples of A53T transgenic mice by real-time quantitative polymerase chain reaction (RT-qPCR). Meanwhile, the expression of the target genes in the olfactory epithelium/bulb was detected by RT-qPCR. Finally, molecular docking was used to screen potential compounds for the target gene. RESULTS: One hundred seventy-four overlapped DEGs were identified in AD and PD. Five of the top ten enrichment pathways mainly focused on the synapse. Five hub genes were identified and further validated. As a common factor in AD and PD, the changes of synaptosomal-associated protein 25 (SNAP25) mRNA in olfactory epithelium/bulb were significantly decreased and had a strong association with those in the HIP and SN samples. Pazopanib was the optimal compound targeting SNAP25, with a binding energy of - 9.2 kcal/mol. CONCLUSIONS: Our results provided a theoretical basis for understanding the comorbidity mechanism of AD and PD and highlighted that SNAP25 in the olfactory epithelium may serve as a potential target for early detection and intervention in both AD and PD.


Subject(s)
Alzheimer Disease , Parkinson Disease , Animals , Mice , Alzheimer Disease/genetics , Alzheimer Disease/metabolism , Gene Expression Profiling , Mice, Transgenic , Molecular Docking Simulation , Parkinson Disease/genetics , Synaptosomal-Associated Protein 25/genetics
15.
J Craniofac Surg ; 2023 Nov 27.
Article in English | MEDLINE | ID: mdl-38011621

ABSTRACT

Microtia is a congenital malformation of the external ear that often presents with other anatomical abnormalities and ipsilateral hearing loss (HL). The aim of this study was to present the correlation among important phenotypic abnormalities in microtia and their relationship with HL in a clinical population in China. In this study, a retrospective analysis was conducted on 307 patients diagnosed with microtia who visited the Department of Auricular Reconstruction of the Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, for surgical auricle reconstruction from April 2021 to April 2022. Standardized classification of ear malformations, craniofacial CT scans, and pure tone audiometric data were collected, and statistical analyses were performed using the rank sum test, Kruskal-Wallis test, and Spearman's rank correlation coefficient. The results showed that group differences between ear malformation and variations in the development of mandible, external auditory canal (EAC), and mastoid pneumatization were statistically significant and each had a positive correlation. Among them, the correlation between development of ear and EAC was the most significant (Ρ=0.72). Besides, the severity of HL (97% were conductive) was positively correlated with ear and EAC dysplasia with or without mandibular hypoplasia. Based on the statistical analysis of the correlation between ear malformation and HL, the authors strongly recommend that facial phenotype reconstruction and hearing improvement of microtia should be considered comprehensively, regardless of whether children with microtia show HL or not, early diagnosis of audiology evaluation and appropriate intervention measures should be implemented.

16.
J Neuroinflammation ; 20(1): 270, 2023 Nov 17.
Article in English | MEDLINE | ID: mdl-37978532

ABSTRACT

BACKGROUND: Subarachnoid hemorrhage (SAH) is an uncommon type of potentially fatal stroke. The pathophysiological mechanisms of brain injury remain unclear, which hinders the development of drugs for SAH. We aimed to investigate the pathophysiological mechanisms of SAH and to elucidate the cellular and molecular biological response to SAH-induced injury. METHODS: A cross-species (human and mouse) multiomics approach combining high-throughput data and bioinformatic analysis was used to explore the key pathophysiological processes and cells involved in SAH-induced brain injury. Patient data were collected from the hospital (n = 712). SAH was established in adult male mice via endovascular perforation, and flow cytometry, a bone marrow chimera model, qPCR, and microglial depletion experiments were conducted to explore the origin and chemotaxis mechanism of the immune cells. To investigate cell effects on SAH prognosis, murine neurological function was evaluated based on a modified Garcia score, pole test, and rotarod test. RESULTS: The bioinformatics analysis confirmed that inflammatory and immune responses were the key pathophysiological processes after SAH. Significant increases in the monocyte levels were observed in both the mouse brains and the peripheral blood of patients after SAH. Ly6C-high monocytes originated in the bone marrow, and the skull bone marrow contribute a higher proportion of these monocytes than neutrophils. The mRNA level of Ccl2 was significantly upregulated after SAH and was greater in CD11b-positive than CD11b-negative cells. Microglial depletion, microglial inhibition, and CCL2 blockade reduced the numbers of Ly6C-high monocytes after SAH. With CCR2 antagonization, the neurological function of the mice exhibited a slow recovery. Three days post-SAH, the monocyte-derived dendritic cell (moDC) population had a higher proportion of TNF-α-positive cells and a lower proportion of IL-10-positive cells than the macrophage population. The ratio of moDCs to macrophages was higher on day 3 than on day 5 post-SAH. CONCLUSIONS: Inflammatory and immune responses are significantly involved in SAH-induced brain injury. Ly6C-high monocytes derived from the bone marrow, including the skull bone marrow, infiltrated into mouse brains via CCL2 secreted from microglia. Moreover, Ly6C-high monocytes alleviated neurological dysfunction after SAH.


Subject(s)
Brain Injuries , Stroke , Subarachnoid Hemorrhage , Humans , Mice , Male , Animals , Monocytes , Subarachnoid Hemorrhage/complications , Brain Injuries/etiology , Macrophages , Mice, Inbred C57BL
17.
MedComm (2020) ; 4(5): e361, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37667740

ABSTRACT

The profile of antibodies against antigenic epitopes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during neutralizing antibody (NAb) decay has not been clarified. Using a SARS-CoV-2 proteome microarray that contained viral antigenic peptides, we analyzed the characteristics of the humoral response in patients with coronavirus disease 19 (COVID-19) in a longitudinal study. A total of 89 patients were recruited, and 226 plasma samples were serially collected in 2020. In the antigenic peptide microarray, the level of immunoglobulin G (IgG) antibodies against peptides within the S2 subunit (S-82) and a conserved gene region in variants of interest, open reading frame protein 10 (ORF10-3), were closely associated with the presence of SARS-CoV-2 NAbs. In an independent evaluation cohort of 232 plasma samples collected from 116 COVID-19 cases in 2020, S82-IgG titers were higher in NAbs-positive samples (p = 0.002) than in NAbs-negative samples using enzyme-linked immunosorbent assay. We further collected 66 plasma samples from another cohort infected by Omicron BA.1 virus in 2022. Compared with the samples with lower S82-IgG titers, NAb titers were significantly higher in the samples with higher S82-IgG titers (p = 0.04). Our findings provide insights into the understanding of the decay-associated signatures of SARS-CoV-2 NAbs.

18.
Ear Nose Throat J ; : 1455613231197768, 2023 Sep 21.
Article in English | MEDLINE | ID: mdl-37735888

ABSTRACT

Objective: Microtia patients with hemifacial microsomia (HFM) have a host of distinct anatomical disorder of skeletal and soft tissue asymmetries. The purpose of this study was to assess soft tissue discrepancies in microtia patients with HFM and their correlation with skeletal discrepancies. Methods: A total of 42 patients were enrolled and studied prospectively using a 3-dimensional superimposition and color mapping of the soft and hard tissues. Mirroring techniques created perfectly symmetric models for comparison. Differences between affected and normal sides were evaluated in 5 areas: retroauricular mastoid, malar, maxillary frontal, mandibular frontal, and gonion areas. Pearson correlations were used to assess the relationship between skeletal and soft tissue asymmetry. Results: Hard tissue asymmetry ranged from 0.79 mm (mandibular frontal) to 1.29 mm (malar), while soft tissue asymmetry ranged from 1.34 mm (maxillary frontal) to 5.26 mm (retroauricular mastoid). Correlations between skeletal and soft tissue asymmetry varied, with the strongest correlation observed at the retroauricular mastoid area and the weakest at the maxillary frontal area. Conclusion: There was a high correlation between bone and soft tissue hypoplasia at the retroauricular mastoid area, while the other evaluated areas showed poor correlation between skeletal and soft tissue asymmetries. Clinicians should assess each component separately for optimal treatment planning in microtia patients with HFM.

19.
Ear Nose Throat J ; : 1455613231198982, 2023 Sep 27.
Article in English | MEDLINE | ID: mdl-37752821

ABSTRACT

Object: Three-stage expansion method represents the most common form of microtia reconstruction in hemifacial microsomia (HFM). Although the complication related expander has lowered owing to the current advances, bony depression in mastoid region in microtia patients with hemifacial microsomia was observed in clinical work. The aim of this study was to quantify bony depression after retroauricular expander implantation and identify associated factors. Methods: 42 patients were enrolled and studied prospectively utilizing 3-dimensional (3D) evaluation. Craniofacial computed tomography (CT) was performed before the first (pre-expansion) and the second stage (post-expansion) and 3D quantification was done to quantify bony depression in mastoid region by using CT data. Univariate analysis was performed to identify factors associated with bony depression in mastoid region. Results: The mean level of mastoid depression was 0.83 mm (range: 0.07-4.08 mm), and the max level of mastoid depression was 1.40 mm (range: 0.20-6.65 mm). In univariate analysis, capsular duration of expansion and expansion volume were associated factors with mastoid depression. Conclusion: This study showed the possibility of mastoid depression following expander implantation for microtia reconstruction in hemifacial microsomia. Plastic surgeons should be aware of the possibility and associated factors of bony depression in mastoid region following expander implantation to optimize microtia reconstruction for patients with HFM.

20.
J Dermatolog Treat ; 34(1): 2248318, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37621164

ABSTRACT

BACKGROUND: Psoriasis is a chronic skin disease, and topical sequential therapy with a combination of calcipotriol and calcipotriol betamethasone is currently approved topical treatment. However, the exact mechanism by which this treatment regimen relieves psoriasis is unknown. METHOD: We assembled a cohort of 65 psoriasis patients and divided post-treatment cohort into responder group and non-responder group according to the Psoriasis Area Severity Index (PASI) score after 12-week treatment. We measured the expression levels of proteins in collected 130 serum samples using our in-depth proteomics platform with a data-independent acquisition mass spectrometer and antibody microarray. We performed bioinformatics analyses of the biologic processes and signaling pathways that were changed in the responder group and constructed a proteomics landscape of psoriasis pathogenesis response to treatment. We then validated the biomarkers of disease severity in an independent cohort of 88 samples using an enzyme-linked immunosorbent assay. RESULTS: We first identified 174 differentially expressed proteins (DEPs) for comparative analysis of proteins between responders and non-responders at baseline (p < 0.05). Then pathway analysis showed that the responders focused more on signaling molecules and interaction, complement and coagulation cascades, whereas the non-responders more on signal transduction and IL-17 signaling pathways. We further identified four candidate biomarkers (COLEC11, C1QA, BNC2, ITIH4) response to treatment. We also found 125 DEPs (p < 0.05) after treatment compared with before treatment in responder group. Pathway analysis showed an enrichment in pathways related to complement and coagulation cascades, phagosome, ECM-receptor interaction, cholesterol metabolism, vitamin digestion and absorption. CD14 was validated as potential biomarkers for the disease severity of psoriasis and treatment targets. CONCLUSION: In this work, we analyzed the response to topical sequential therapy and finally identified four biomarkers. Additionally, we found that topical sequential therapy may alleviate psoriasis by regulating lipid metabolism and modulating the immune response by affecting the complement activation process.


Subject(s)
Proteomics , Psoriasis , Humans , Psoriasis/drug therapy , Betamethasone/therapeutic use , Biomarkers , Computational Biology
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