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1.
Mitochondrion ; : 101932, 2024 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-38986922

RESUMO

SIRT6, an evolutionarily conserved histone deacetylase, has been identified as a novel direct downstream target of Akt/FoxO3a and a tumor suppressor in colon cancer in our previous research. Nevertheless, the precise mechanisms through which SIRT6 hinders tumor development remain unclear. To ascertain whether SIRT6 directly impacts Survivin transcription, a ChIP assay was conducted using an anti-SIRT6 antibody to isolate DNA. YM155 was synthesized to explore Survivin's role in mitochondrial apoptosis, autophagy and tumor progression. Our investigation into the regulation of Survivin involved real-time fluorescence imaging in living cells, real-time PCR, immunohistochemistry, flow cytometry, and xenograft mouse assays. In this current study, we delved into the role of SIRT6 in colon cancer and established that activated SIRT6 triggers mitochondrial apoptosis by reducing Survivin expression. Subsequent examinations revealed that SIRT6 directly binds to the Survivin promoter, impeding its transcription. Notably, direct inhibition of Survivin significantly impeded colon cancer proliferation by inducing mitochondrial apoptosis and autophagy both in vitro and in vivo. More interestingly, Survivin inhibition reactivated the Akt/FoxO3a pathway and elevated SIRT6 levels, establishing a positive feedback loop. Our results identify Survivin as a novel downstream transcriptional target of SIRT6 that fosters tumor growth and holds promise as a prospective target for colon cancer therapy.

2.
Appl Opt ; 63(11): 2822-2830, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38856377

RESUMO

Local phase retardation (LPR) is increasingly recognized as a crucial biomarker for assessing disease progression. However, the presence of speckle noise significantly challenges its accuracy and polarization contrast. To address this challenge, we propose a signal-processing strategy aimed at reducing the impact of noise on LPR measurements. In this approach, the LPR is reconstructed by polar decomposition after averaging multiple Mueller matrices from different overlapping sub-spectra. To optimize measurement accuracy, we systematically combined and traversed different sub-spectral numbers and bandwidths. By examining the quarter-wave plate and glass slide, high-accuracy phase retardation measurements were successfully verified, and the maximum polarization contrast was improved by 23%. Moreover, experimental results from multi-tissue imaging vividly illustrate that the equivalent number of looks (ENL) and polarization contrast were improved by 18% and 19%, respectively. This outcome indicates that our proposed strategy can effectively reduce the noise spikes, enhancing tissue discrimination capabilities.

3.
Appl Opt ; 63(13): 3381-3389, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38856522

RESUMO

The collinear reflection Mueller matrix imaging polarimeter is suitable for characterizing thick samples with high-scattering depolarization such as biological tissues or in-situ living organs. Achieving fast detection and high measurement accuracy is vital to prevent artifacts and accurately assess polarization characteristics in these applications. This paper demonstrates a fast collinear reflection imaging polarimeter based on liquid crystal variable retarders (LCVRs-CRMMIP). We propose a novel compound calibration method (CCM), to the best of our knowledge, which enhances measurement accuracy through light intensity correction and an improved equivalent calibration sample model. This method surpasses the double-pass eigenvalue calibration method (dp-ECM), enhancing accuracy by over 23 times. Performance evaluations with standard samples, including mirrors, linear polarizers, and wave plates, reveal that the LCVRs-CRMMIP achieves rapid measurements (about 3 s) and high accuracy with an error of less than 0.0017.

4.
Spectrochim Acta A Mol Biomol Spectrosc ; 320: 124603, 2024 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-38878720

RESUMO

Iron-sulfur cluster conversion and nitrosyl modification are involved in regulating their functions and play critical roles in signaling for biological systems. Hereby, the photo-induced dynamic process of (Me4N)2[Fe2S2(NO)4] was monitored using time-resolved electron paramagnetic resonance (EPR) spectra, MS spectra and cellular imaging methods. Photo-irradiation and the solvent affect the reaction rates and products. Spectroscopic and kinetic studies have shown that the process involves at least three intermediates: spin-trapped NO free radical species with a gav at 2.040, and two other iron nitrosyl species, dinitrosyl iron units (DNICs) and mononitrosyl iron units (MNICs) with gav values at 2.031 and 2.024, respectively. Moreover, the [Fe2S2(NO)4]2- cluster could bind with ferritin and decompose gradually, and a binding state of dinitrosyl iron coordinated with Cys102 of the recombinant human heavy chain ferritin (rHuHF) was finally formed. This study provides insight into the photodynamic mechanism of nitrosyl iron - sulfur clusters to improve the understanding of physiological activity.


Assuntos
Ferro , Humanos , Espectroscopia de Ressonância de Spin Eletrônica , Ferro/química , Ferro/metabolismo , Óxidos de Nitrogênio/química , Óxidos de Nitrogênio/metabolismo , Ligação Proteica , Cinética , Proteínas Ferro-Enxofre/metabolismo , Proteínas Ferro-Enxofre/química , Enxofre/química , Enxofre/metabolismo , Ferritinas/química , Ferritinas/metabolismo , Luz
5.
Eur J Pharmacol ; 977: 176708, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-38843945

RESUMO

Excessive transforming growth factor ß1 (TGF-ß1) secreted by activated hepatic stellate cells (aHSCs) aggravates liver fibrosis via over-activation of TGF-ß1-mediated signaling pathways in a TGF-ß type I receptor (TßRI) dependent manner. TßRI with the C-terminal valine truncated (RIPΔ), as a novel TßRI-mimicking peptide, is an appealing anti-fibrotic candidate by competitive binding of TGF-ß1 to block TGF-ß1 signal transduction. Platelet-derived growth factor receptor ß (PDGFßR) is highly expressed on the surface of aHSCs in liver fibrosis. Herein, we designed a novel RIPΔ variant Z-RIPΔ (PDGFßR-specific affibody ZPDGFßR fused to the N-terminus of RIPΔ) for liver fibrosis therapy, and expect to improve the anti-liver fibrosis efficacy by specifically inhibiting the TGF-ß1 activity in aHSCs. Target peptide Z-RIPΔ was prepared in Escherichia coli by SUMO fusion system. Moreover, Z-RIPΔ specifically bound to TGF-ß1-activated aHSCs, inhibited cell proliferation and migration, and reduced the expression of fibrosis markers (α-SMA and FN) and TGF-ß1 pathway-related effectors (p-Smad2/3 and p-p38) in vitro. Furthermore, Z-RIPΔ specifically targeted the fibrotic liver, alleviated the liver histopathology, mitigated the fibrosis responses, and blocked TGF-ß1-mediated Smad and p38 MAPK cascades. More importantly, Z-RIPΔ exhibited a higher fibrotic liver-targeting capacity and stronger anti-fibrotic effects than its parent RIPΔ. Besides, Z-RIPΔ showed no obvious toxicity effects in treating both an in vitro cell model and an in vivo mouse model of liver fibrosis. In conclusion, Z-RIPΔ represents a promising targeted candidate for liver fibrosis therapy.


Assuntos
Células Estreladas do Fígado , Cirrose Hepática , Receptor do Fator de Crescimento Transformador beta Tipo I , Transdução de Sinais , Proteínas Smad , Fator de Crescimento Transformador beta1 , Proteínas Quinases p38 Ativadas por Mitógeno , Células Estreladas do Fígado/efeitos dos fármacos , Células Estreladas do Fígado/metabolismo , Células Estreladas do Fígado/patologia , Animais , Fator de Crescimento Transformador beta1/metabolismo , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/patologia , Cirrose Hepática/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Camundongos , Proteínas Smad/metabolismo , Masculino , Receptor do Fator de Crescimento Transformador beta Tipo I/metabolismo , Receptor do Fator de Crescimento Transformador beta Tipo I/antagonistas & inibidores , Transdução de Sinais/efeitos dos fármacos , Peptídeos/farmacologia , Peptídeos/química , Humanos , Camundongos Endogâmicos C57BL
6.
Artigo em Inglês | MEDLINE | ID: mdl-38943533

RESUMO

BACKGROUND: We aimed to verify the effectiveness of electroacupuncture on postoperative ileus prevention after abdominal surgery by meta-analysis and trial sequential analysis (TSA). METHODS: From inception to May 14, 2024, PubMed, the Cochrane Library, Web of Science, and Embase databases were searched. TSA was used to determine an optimal sample size and control false-positive findings. The primary outcome was the time to first defecation (hours). RESULTS: Fourteen studies were included, with 1105 participants. Meta-analysis and TSA revealed firm evidence for benefits that electroacupuncture shorted the time to first defecation (mean difference [MD] -12.73 h, I2 = 22%, P < 0.01), the time to first flatus (MD -7.03 h, I2 = 25%, P < 0.01), the time to start of sips of water (MD -12.02 h, I2 = 0%, P < 0.01), and the time to start of liquid diet (MD -12.97 h, I2 = 0%, P < 0.01) compared with usual care. While compared with sham electroacupuncture, meta-analysis and TSA also confirmed that electroacupuncture shortened the time to first defecation (MD -10.81 h, I2 = 31%, P = 0.02) and the time to first flatus (MD -10.81 h, I2 = 0%, P < 0.01). However, TSA revealed that firm evidence for benefit or futility was not reached for the length of hospital stay and the rates of postoperative prolonged ileus. CONCLUSIONS: Electroacupuncture shortened the duration of postoperative ileus in patients undergoing abdominal surgery, and the adverse events related to electroacupuncture were minor. Further investigation of the effect of electroacupuncture on the risk of prolonged postoperative ileus is warranted in the future.

7.
Opt Lett ; 49(12): 3464-3467, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38875646

RESUMO

Existing polarimetry, mainly focusing on harmonic generations, overlooks the differences in retardance (DRs) caused by illuminations with different wavelengths in nonlinear processes, consequently falling short in accuracy beyond frequency doubling. In this Letter, with DRs considered, we propose a universal nonlinear Stokes-Mueller (NSM) polarimetry design involving illuminations with different wavelengths. Then, we optimize the NSM measurement model, applied to sum-frequency generation (SFG) and difference frequency generation. To demonstrate the necessity of consideration of DRs, the processes of polarization measurement for SFG are simulated, where the condition number decreases by 51.2%, and the root mean square error of the nonlinear Mueller matrix decreases by 20.48%.

8.
Cell Death Dis ; 15(5): 350, 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38773070

RESUMO

Seipin is one key mediator of lipid metabolism that is highly expressed in adipose tissues as well as in the brain. Lack of Seipin gene, Bscl2, leads to not only severe lipid metabolic disorders but also cognitive impairments and motor disabilities. Myelin, composed mainly of lipids, facilitates nerve transmission and is important for motor coordination and learning. Whether Seipin deficiency-leaded defects in learning and motor coordination is underlined by lipid dysregulation and its consequent myelin abnormalities remains to be elucidated. In the present study, we verified the expression of Seipin in oligodendrocytes (OLs) and their precursors, oligodendrocyte precursor cells (OPCs), and demonstrated that Seipin deficiency compromised OPC differentiation, which led to decreased OL numbers, myelin protein, myelinated fiber proportion and thickness of myelin. Deficiency of Seipin resulted in impaired spatial cognition and motor coordination in mice. Mechanistically, Seipin deficiency suppressed sphingolipid metabolism-related genes in OPCs and caused morphological abnormalities in lipid droplets (LDs), which markedly impeded OPC differentiation. Importantly, rosiglitazone, one agonist of PPAR-gamma, substantially restored phenotypes resulting from Seipin deficiency, such as aberrant LDs, reduced sphingolipids, obstructed OPC differentiation, and neurobehavioral defects. Collectively, the present study elucidated how Seipin deficiency-induced lipid dysregulation leads to neurobehavioral deficits via impairing myelination, which may pave the way for developing novel intervention strategy for treating metabolism-involved neurological disorders.


Assuntos
Diferenciação Celular , Disfunção Cognitiva , Subunidades gama da Proteína de Ligação ao GTP , Bainha de Mielina , Células Precursoras de Oligodendrócitos , Animais , Subunidades gama da Proteína de Ligação ao GTP/metabolismo , Subunidades gama da Proteína de Ligação ao GTP/genética , Camundongos , Células Precursoras de Oligodendrócitos/metabolismo , Bainha de Mielina/metabolismo , Disfunção Cognitiva/metabolismo , Disfunção Cognitiva/patologia , Disfunção Cognitiva/genética , Metabolismo dos Lipídeos , Oligodendroglia/metabolismo , Oligodendroglia/patologia , Camundongos Endogâmicos C57BL , PPAR gama/metabolismo , PPAR gama/genética , Camundongos Knockout , Masculino , Rosiglitazona/farmacologia
9.
Appl Opt ; 63(9): 2331-2339, 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38568589

RESUMO

A new method, to the best of our knowledge, based on double-slit (DS) interference is proposed to accurately estimate the shear ratio of the system, with plane wave or spherical wave incidence. Existing shear ratio calibration methods, designed primarily for lateral shearing interferometry (LSI) with plane wave incidence, are not applicable to LSIs directly testing divergent or convergent spherical waves. Equations for calculating the shear ratio using the fringe spacing of the DS interferogram and the NA of the incident spherical wave are derived in this paper. The simulation result shows that the relative error of the shear ratio value is about 0.3%, when the shear ratio is 0.1. In the experiment, the quadriwave LSI is designed with a plug-in feature. The shear ratio at integer multiples of 1/6 Talbot distance from the modified Hartmann mask was calibrated using a DS, and the results were in good agreement with theoretical values, confirming the accuracy of the method. Subsequently, with the assistance of an inductance micrometer, the shear ratio was calibrated at intervals of 0.5 mm, and the results closely matched the theoretical variation of the shear ratio caused by displacement, confirming the high precision of the method.

11.
Front Endocrinol (Lausanne) ; 15: 1364316, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38590823

RESUMO

Background: Leukemia patients undergoing cryopreserved ovarian tissue transplantation (OTT) may carry a high risk of disease induction. Measurable residual disease (MRD) in bone marrow is linked to an elevated risk of relapse. It is controversial whether leukemia patients must be allowed to achieve measurable residual disease negative (MRD-negative) status instead of measurable residual disease positive (MRD-positive) status before ovarian tissue cryopreservation (OTC). Objective: To explore the safety and efficacy of OTT in acute leukemia patients with different MRD status by using xenotransplantation. Method: Cryopreserved ovarian tissue from 19 leukemia patients was thawed and xenotransplanted to ovariectomized BALB/C nude mice (n=36). The mice were divided into 2 groups based on the patient's MRD status before OTC: MRD-negative group (n=18) and MRD-positive group (n=18), additionally, a control group consisted of ovariectomized mice (n=9). Body weight was measured weekly and mortality, emaciation, and other abnormalities were recorded. Twenty-six weeks post-surgery, livers, spleens, uteruses, and ovarian grafts were removed for macroscopic and histological examinations to evaluate the efficacy of xenotransplantation and assess malignant cell contamination in mice. Results: Follicle growth was visible in the ovarian grafts of the MRD-negative and MRD-positive groups. Compared with the ovariectomized group, a significant decrease in body weight (p<0.01) was noted, the uterine volume was notably larger, estradiol (E2) levels were significantly higher (p<0.01), and follicle-stimulating hormone (FSH) levels were significantly lower (p<0.001) in the other two groups. Mice in the MRD-positive group showed a significantly higher incidence of death (p<0.001) and emaciation (p<0.01), compared to the MRD-negative group. Histological observation revealed the presence of malignant cells in the grafts, livers, and spleens of 3 mice in the MRD-positive group. No abnormalities were observed in the mice from the MRD-negative group in both macroscopic and histological observations except one mouse was sacrificed for ascites unrelated to leukemia relapse. Conclusion: For leukemia patients having ovarian tissue preserved in the first and only centralized human ovarian tissue cryobank in China, immunodeficient mice xenotransplantation can be a method to evaluate the safety and efficacy of OTT; the risk of malignant cell reimplantation due to OTT is higher in leukemia patients with MRD-positive status than those with MRD-negative status before OTC.


Assuntos
Medula Óssea , Leucemia , Feminino , Humanos , Animais , Camundongos , Transplante Heterólogo , Camundongos Nus , Emaciação , Camundongos Endogâmicos BALB C , Criopreservação , Recidiva
12.
Angew Chem Int Ed Engl ; 63(27): e202402800, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38411404

RESUMO

π-Conjugated chiral nanorings with intriguing electronic structures and chiroptical properties have attracted considerable interests in synthetic chemistry and materials science. We present the design principles to access new chiral macrocycles (1 and 2) that are essentially built on the key components of main-group electron-donating carbazolyl moieties or the π-expanded aza[7]helicenes. Both macrocycles show the unique molecular conformations with a (quasi) figure-of-eight topology as a result of the conjugation patterns of 2,2',7,7'-spirobifluorenyl in 1 and triarylamine-coupled aza[7]helicene-based building blocks in 2. This electronic nature of redox-active, carbazole-rich backbones enabled these macrocycles to be readily oxidized chemically and electrochemically, leading to the sequential production of a series of positively charged polycationic open-shell cyclophanes. Their redox-dependent electronic states of the resulting multispin polyradicals have been characterized by VT-ESR, UV/Vis-NIR absorption and spectroelectrochemical measurements. The singlet (ΔES-T=-1.29 kcal mol-1) and a nearly degenerate singlet-triplet ground state (ΔES-T(calcd)=-0.15 kcal mol-1 and ΔES-T(exp)=0.01 kcal mol-1) were proved for diradical dications 12+2⋅ and 22+2⋅, respectively. Our work provides an experimental proof for the construction of electron-donating new chiral nanorings, and more importantly for highly charged polyradicals with potential applications in chirospintronics and organic conductors.

13.
Autoimmunity ; 57(1): 2319204, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38409788

RESUMO

Background: Lupus Nephritis (LN) is the primary causation of kidney injury in systemic lupus erythematosus (SLE). Ferroptosis is a programmed cell death. Therefore, understanding the crosstalk between LN and ferroptosis is still a significant challenge. Methods: We obtained the expression profile of LN kidney biopsy samples from the Gene Expression Omnibus database and utilised the R-project software to identify differentially expressed genes (DEGs). Then, we conducted a functional correlation analysis. Ferroptosis-related genes (FRGs) and differentially expressed genes (DEGs) crossover to select FRGs with LN. Afterwards, we used CIBERSORT to assess the infiltration of immune cells in both LN tissues and healthy control samples. Finally, we performed immunohistochemistry on LN human renal tissue. Results: 10619 DEGs screened from the LN biopsy tissue were identified. 22 hub-ferroptosis-related genes with LN (FRGs-LN) were screened out. The CIBERSORT findings revealed that there were significant statistical differences in immune cells between healthy control samples and LN tissues. Immunohistochemistry further demonstrated a significant difference in HRAS, TFRC, ATM, and SRC expression in renal tissue between normal and control groups. Conclusion: We developed a signature that allowed us to identify 22 new biomarkers associated with FRGs-LN. These findings suggest new insights into the pathology and therapeutic potential of LN ferroptosis inhibitors and iron chelators.


Assuntos
Ferroptose , Lúpus Eritematoso Sistêmico , Nefrite Lúpica , Humanos , Nefrite Lúpica/genética , Ferroptose/genética , Apoptose , Biópsia
14.
Zhen Ci Yan Jiu ; 49(1): 79-87, 2024 Jan 25.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-38239142

RESUMO

Acupuncture treatment for functional constipation (FC) is characterized by precise efficacy, rapid onset of action in the early stages, long-term stable effects, and overall regulation. This paper reviews recent literatures on acupuncture treatment for FC, indicating that acupuncture acts from multiple perspectives and pathways, including promoting intestinal motility, regulating intestinal microbiota, modulating the brain-gut axis, alleviating intestinal inflammation, and improving rectal hyposensitivity. Future research could delve into the mechanical sensation conduction mechanisms of acupuncture in improving rectal hyposensitivity, identify key intestinal microbiota genera and metabolic characteristics regulated by acupuncture, explore the network relationships among different mechanisms, and clarify the differential mechanisms of various acupuncture treatment protocols to optimize clinical therapy and enhance the clinical efficacy of acupuncture for FC.


Assuntos
Terapia por Acupuntura , Constipação Intestinal , Humanos , Constipação Intestinal/terapia , Terapia por Acupuntura/métodos , Resultado do Tratamento , Motilidade Gastrointestinal , Sensação
15.
Appl Opt ; 63(2): 327-337, 2024 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-38227225

RESUMO

Source mask optimization (SMO) is a widely used computational lithography technique for compensating lithographic distortion. However, line-end shortening is still a key factor that cannot be easily corrected and affects the image fidelity of lithography at advanced nodes. This paper proposes a source mask optimization method that suppresses line-end shortening and improves lithography fidelity. An adaptive hybrid weight method is employed to increase the weights of the line end during the optimization, which adaptively updates the weights in each iteration according to the edge placement error (EPE). A cost function containing a penalty term based on the normalized image log slope (NILS) is established to ensure the fidelity of the overall feature when paying more attention to the line-end region. The scope of this penalty term is regulated by widening and extending the split contour to further reduce the line-end shortening. Simulation results show that the proposed method can effectively suppress the line-end shortening and improve the lithography fidelity compared with the traditional SMO method.

16.
Sci Total Environ ; 914: 169725, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38190903

RESUMO

In this study, metal-organic framework (MOF) nanofiber membranes (NFMs) UiO-66-Lys/PAN were prepared by electrospinning using polyacrylonitrile (PAN) as the matrix, UiO-66-NH2 as the filler, and lysine (Lys) as the functional monomer. The membranes were subsequently employed to extract cobalt ions from simulated radioactive wastewater. The findings showed that the best performance of the membrane was obtained with a 3 % MOF content (3%UiO-66-Lys/PAN). Specifically, the pure water flux (PWF) of the 3 % UiO-66-Lys/PAN membrane reached 872 L m-2 h-1 with a cobalt ion retention of 45.4 %. In addition, adsorption experiments indicated that the NFMs had a theoretical maximum adsorption capacity of 41.4 mg/g for cobalt ions. The Langmuir isotherm model and the pseudo-second-order kinetic model were observed in the adsorption process, suggesting that the membrane material showed uniform adsorption of cobalt ions on a monolayer level, with an endothermic absorption process. XPS analysis confirmed that 3%UiO-66-Lys/PAN facilitated the adsorption of cobalt ions through a coordination effect, with the N and O atoms serving as coordinating atoms. Moreover, the material displayed excellent radiation stability even when exposed to doses ranging from 20 to 200 kGy. This study validated the stability of the MOF NFMs under real irradiation with radioactive nuclides (60Co) and demonstrated efficient cobalt ion separation. This study has important practical implications for the treatment and disposal of small volumes of 60Co-containing radioactive wastewater for engineering applications.

17.
Chin J Integr Med ; 30(3): 251-259, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38212498

RESUMO

OBJECTIVE: To explore the mechanism of electroacupuncture (EA) in promoting recovery of the facial function with the involvement of autophagy, glial cell line-derived neurotrophic factor (GDNF), and phosphatidylinositol-3-kinase (PI3K)/mammalian target of rapamycin (mTOR) signaling pathway. METHODS: Seventy-two male Sprague-Dawley rats were randomly allocated into the control, sham-operated, facial nerve injury (FNI), EA, EA+3-methyladenine (3-MA), and EA+GDNF antagonist groups using a random number table, with 12 rats in each group. An FNI rat model was established with facial nerve crushing method. EA intervention was conducted at Dicang (ST 4), Jiache (ST 6), Yifeng (SJ 17), and Hegu (LI 4) acupoints for 2 weeks. The Simone's 10-Point Scale was utilized to monitor the recovery of facial function. The histopathological evaluation of facial nerves was performed using hematoxylin-eosin (HE) staining. The levels of Beclin-1, light chain 3 (LC3), and P62 were detected by immunohistochemistry (IHC), immunofluorescence, and reverse transcription-polymerase chain reaction, respectively. Additionally, IHC was also used to detect the levels of GDNF, Rai, PI3K, and mTOR. RESULTS: The facial functional scores were significantly increased in the EA group than the FNI group (P<0.05 or P<0.01). HE staining showed nerve axons and myelin sheaths, which were destroyed immediately after the injury, were recovered with EA treatment. The expressions of Beclin-1 and LC3 were significantly elevated and the expression of P62 was markedly reduced in FNI rats (P<0.01); however, EA treatment reversed these abnormal changes (P<0.01). Meanwhile, EA stimulation significantly increased the levels of GDNF, Rai, PI3K, and mTOR (P<0.01). After exogenous administration with autophagy inhibitor 3-MA or GDNF antagonist, the repair effect of EA on facial function was attenuated (P<0.05 or P<0.01). CONCLUSIONS: EA could promote the recovery of facial function and repair the facial nerve damages in a rat model of FNI. EA may exert this neuroreparative effect through mediating the release of GDNF, activating the PI3K/mTOR signaling pathway, and further regulating the autophagy of facial nerves.


Assuntos
Eletroacupuntura , Traumatismos do Nervo Facial , Ratos , Masculino , Animais , Ratos Sprague-Dawley , Fosfatidilinositol 3-Quinase/metabolismo , Traumatismos do Nervo Facial/terapia , Fosfatidilinositol 3-Quinases/metabolismo , Proteína Beclina-1 , Fator Neurotrófico Derivado de Linhagem de Célula Glial , Transdução de Sinais , Serina-Treonina Quinases TOR/metabolismo , Autofagia , Mamíferos/metabolismo
18.
J Invest Dermatol ; 144(1): 63-72.e4, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-37517516

RESUMO

Ubiquitin-specific protease 15 (USP15) plays a significant role in regulating various biological processes in several autoimmune diseases and cancers. However, its role in psoriatic keratinocytes (KCs) has not been extensively studied. In this study, we described that USP15 promotes proliferation and inflammation in KCs by stabilizing squamous cell carcinoma antigen 2. We discovered that the expression of USP15 and squamous cell carcinoma antigen 2 was elevated in lesions from patients with clinical psoriasis and an imiquimod-induced psoriatic dermatitis mouse model. USP15 was able to bind, deubiquitinate, and stabilize squamous cell carcinoma antigen 2. Knocking down USP15 resulted in reduced KC inflammation and impaired KC viability and clonogenicity. Topically applying USP15 small interfering RNA significantly ameliorated imiquimod-induced psoriatic dermatitis and reduced the infiltration of T cells and neutrophils. In addition, we determined that IL-22 was a key cytokine that upregulated the expression of USP15. These findings provide insights regarding the mechanisms involved in the proliferation and inflammation of KCs mediated by IL-22, suggesting a potential IL-22-USP15-squamous cell carcinoma antigen 2 axis in the pathogenesis of psoriatic KCs.


Assuntos
Dermatite , Interleucina 22 , Camundongos , Animais , Humanos , Imiquimode , Queratinócitos/metabolismo , Inflamação/patologia , Dermatite/patologia , Proliferação de Células , Proteases Específicas de Ubiquitina/genética , Proteases Específicas de Ubiquitina/metabolismo
19.
Front Microbiol ; 14: 1320567, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38125567

RESUMO

Introduction: Gut microbiota and metabolites have been identified to contribute to the pathogenesis of functional constipation (FC); however, the underlying mechanism(s) have not been elucidated, and the relationship between the gut microbiota and metabolites in FC has received limited attention in the literature. Methods: 16S rDNA sequencing and non-targeted metabolomic detection based on liquid chromatography-mass spectrometry (LC-MS/MS) technologies were combined to analyze the altered gut microbiome and metabolic profile of fecal samples from FC patients and healthy individuals (healthy control; HC). Results: The richness and diversity of gut microbiota significantly (p < 0.01) increased in FC patients. Compared to the HC group, 18 genera, including Intestinibacter, Klebsiella, and Akkermansia, exhibited statistically significant changes (p < 0.05). Metabolic analysis showed that metabolic profiles were also markedly altered with 79 metabolites, such as (-)-caryophyllene oxide, chenodeoxycholic acid, and biliverdin, indicating significant inter-group differences (p < 0.05). Besides, the primary bile acid biosynthesis, as well as the metabolic profile of porphyrin and chlorophyll, were the most dominant enriched pathways (FDR < 0.01), in which chenodeoxycholic acid and biliverdin were significantly enriched, respectively. Correlation analysis demonstrated a strong relationship between 10 genera and 19 metabolites (r > 0.6, FDR < 0.05), and notably, Intestinibacter showed a negative correlation with biliverdin (FDR < 0.001), which highlighted the interplay of the gut microbiota and metabolites in the pathogenesis of FC. Conclusion: Our research describes the characteristics of the gut microbiota and metabolic profiles and the correlation between the gut microbiota and metabolites in FC patients. This may contribute to the understanding of the underlying mechanisms involved in FC pathogenesis and may provide novel insights into therapeutic interventions.

20.
Appl Opt ; 62(34): 9009-9017, 2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-38108736

RESUMO

Polarization measurement is generally performed in scenes with a low signal-to-noise ratio (SNR) such as remote sensing and biological tissue detection. The spatially modulated polarimeter can satisfy the real-time measurement requirements in low SNR scenes by establishing the mapping between photon spatial distribution and polarization information. However, accurately measuring the polarization state under low-light illumination becomes highly challenging owing to the interference of background noise. In this paper, a deep learning method is proposed and applied to the high-accuracy reconstruction of polarization information at low light field. A reinforced two-layer deep convolutional neural network is designed to respectively extract global and local features of noise in this method. Accurate photon spatial distribution can be obtained by fusing and processing these features. Experimental results illustrate the excellent accuracy achieved by the proposed method with a maximum average value of the absolute measured error below 0.04. More importantly, the proposed method is well-performed for the reconstruction of Stokes vectors at low light fields of various levels without requiring changes to the model, enhancing its practicality and simplicity.

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