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1.
Acta Pharm Sin B ; 14(4): 1772-1786, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38572096

RESUMO

Human monoamine oxidase B (hMAO-B) has emerged as a pivotal therapeutic target for Parkinson's disease. Due to adverse effects and shortage of commercial drugs, there is a need for novel, highly selective, and reversible hMAO-B inhibitors with good blood-brain barrier permeability. In this study, a high-throughput at-line nanofractionation screening platform was established with extracts from Chuanxiong Rhizoma, which resulted in the discovery of 75 active compounds, including phenolic acids, volatile oils, and phthalides, two of which were highly selective novel natural phthalide hMAO-B inhibitors that were potent, selective, reversible and had good blood‒brain permeability. Molecular docking and molecular dynamics simulations elucidated the inhibition mechanism. Sedanolide (IC50 = 103 nmol/L; SI = 645) and neocnidilide (IC50 = 131 nmol/L; SI = 207) demonstrated their excellent potential as hMAO-B inhibitors. They offset the limitations of deactivating enzymes associated with irreversible hMAO-B inhibitors such as rasagiline. In SH-SY5Y cell assays, sedanolide (EC50 = 0.962 µmol/L) and neocnidilide (EC50 = 1.161 µmol/L) exhibited significant neuroprotective effects, comparable to the positive drugs rasagiline (EC50 = 0.896 µmol/L) and safinamide (EC50 = 1.079 µmol/L). These findings underscore the potential of sedanolide as a novel natural hMAO-B inhibitor that warrants further development as a promising drug candidate.

2.
Oncol Lett ; 27(6): 245, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38638846

RESUMO

[This corrects the article DOI: 10.3892/ol.2018.8364.].

3.
Transl Oncol ; 44: 101932, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38492500

RESUMO

The genome of oral squamous cell carcinoma (OSCC) has been extensively characterized via bulk sequencing, revealing a multitude of genetic changes. The gene IGF2BP3, which encodes for the insulin-like growth factor 2 mRNA-binding protein 3, has been observed to be highly expressed in several types of cancer. This finding suggests that IGF2BP3 may play a significant role in the initiation and advancement of cancer. Nevertheless, the mechanisms by which IGF2BP3 contribute to OSCC are yet to be fully understood. In this study, we have observed that IGF2BP3 exhibits overexpression in OSCC. Based on our findings from bulk sequencing analysis, we have concluded that IGF2BP3 could potentially serve as a biomarker for predicting poor prognosis in OSCC. Moreover, it has been demonstrated that IGF2BP3 exhibits a significant association with the initiation and advancement of tumors both in vivo and in vitro. The evaluation of IGF2BP3 expression levels in relation to the cell cycle stage was conducted using single-cell RNA sequencing data. Tumor cells characterized by elevated IGF2BP3 expression demonstrated a higher percentage of cells in the G2/M transition phase. This study presents new findings indicating that the molecular target IGF2BP3 can serve as a prognostic indicator for tumors and has an impact on the development and progression of OSCC by influencing the regulation of the cell cycle.

4.
J Int Med Res ; 52(3): 3000605241236050, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38520253

RESUMO

OBJECTIVE: Acute respiratory infections are a major global public health concern. However, there are few epidemiological studies investigating pathogens associated with respiratory tract infections in Guizhou Province, China. METHODS: We collected 17,850 blood samples from Guizhou Provincial People's Hospital between November 2018 and May 2023 to investigate the epidemiological characteristics of respiratory pathogens and their spread during the SARS-CoV-2 epidemic in Guizhou Province. RESULTS: We identified influenza virus and Mycoplasma pneumoniae as the predominant pathogens involved in acute respiratory infections in the study area. Immunoglobulin M positivity for respiratory syncytial virus, influenza virus, and M. pneumoniae showed a strong correlation with the clinical diagnosis of pneumonia. Seasonal epidemic patterns were observed for influenza A and B viruses. Following the SARS-CoV-2 outbreak, there was a significant decrease in the positive rates for most respiratory pathogens, particularly influenza A and B, Legionella pneumophila, and respiratory syncytial virus. CONCLUSION: This retrospective study contributes to the epidemiological evidence regarding respiratory pathogens in Guizhou Province, thereby enhancing the surveillance network for respiratory pathogens in China and providing valuable guidance for local hospitals.


Assuntos
COVID-19 , Influenza Humana , Infecções Respiratórias , Humanos , Influenza Humana/epidemiologia , SARS-CoV-2 , Estudos Retrospectivos , COVID-19/epidemiologia , COVID-19/complicações , Infecções Respiratórias/epidemiologia , Infecções Respiratórias/diagnóstico , China/epidemiologia , Mycoplasma pneumoniae
5.
J Med Microbiol ; 73(3)2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38506717

RESUMO

Purpose. Metagenomic next-generation sequencing (mNGS) has been widely used in the diagnosis of infectious diseases, while its performance in diagnosis of tuberculous meningitis (TBM) is incompletely characterized. The aim of this study was to assess the performance of mNGS in the diagnosis of TBM, and illustrate the sensitivity and specificity of different methods.Methods. We retrospectively recruited TBM patients between January 2021 and March 2023 to evaluate the performance of mNGS on cerebrospinal fluid (CSF) samples, in comparison with conventional microbiological testing, including culturing of Mycobacterium tuberculosis (MTB), acid-fast bacillus (AFB) stain, reverse transcription PCR and Xpert MTB/RIF.Results. Of the 40 enrolled, 34 participants were diagnosed with TBM, including 15(44.12 %) definite and 19(55.88 %) clinical diagnosis based upon clinical manifestations, CSF parameters, brain imaging, pathogen evidence and treatment response. The mNGS method identified sequences of Mycobacterium tuberculosis complex (MTBC) in 11 CSF samples. In patients with definite TBM, the sensitivity, specificity, positive predictive value, negative predictive value and accuracy of mNGS were 78.57, 100, 100, 66.67 and 85 %, respectively. Compared to conventional diagnostic methods, the sensitivity of mNGS (78.57 %) was higher than AFB (0 %), culturing (0 %), RT-PCR (60 %) and Xpert MTB/RIF (14.29 %).Conclusions. Our study indicates that mNGS of CSF exhibited an overall improved sensitivity over conventional diagnostic methods for TBM and can be considered a front-line CSF test.


Assuntos
Mycobacterium tuberculosis , Tuberculose Meníngea , Humanos , Tuberculose Meníngea/diagnóstico , Estudos Retrospectivos , Sequenciamento de Nucleotídeos em Larga Escala , Mycobacterium tuberculosis/genética , Encéfalo
6.
Adv Sci (Weinh) ; : e2308783, 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38509587

RESUMO

As the population ages, the worldwide prevalence of Alzheimer's disease (AD) as the most common dementia in the elderly is increasing dramatically. However, a long-term challenge is to achieve rapid and accurate early diagnosis of AD by detecting hallmarks such as amyloid beta (Aß42). Here, a multi-channel microfluidic-based plasmonic fiber-optic biosensing platform is established for simultaneous detection and differentiation of multiple AD biomarkers. The platform is based on a gold-coated, highly-tilted fiber Bragg grating (TFBG) and a custom-developed microfluidics. TFBG excites a high-density, narrow-cladding-mode spectral comb that overlaps with the broad absorption of surface plasmons for high-precision interrogation, enabling ultrasensitive monitoring of analytes. In situ detection and in-parallel discrimination of different forms of Aß42 in cerebrospinal fluid (CSF) are successfully demonstrated with a detection of limit in the range of ≈30-170 pg mL-1, which is one order of magnitude below the clinical cut-off level in AD onset, providing high detection sensitivity for early diagnosis of AD. The integration of the TFBG sensor with multi-channel microfluidics enables simultaneous detection of multiple biomarkers using sub-µL sample volumes, as well as combining initial binding rate and real-time response time to differentiate between multiple biomarkers in terms of binding kinetics. With the advantages of multi-parameter, low consumption, and highly sensitive detection, the sensor represents an urgently needed potentials for large-scale diagnosis of diseases at early stage.

7.
J Esthet Restor Dent ; 36(3): 437-444, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38303586

RESUMO

OBJECTIVE: This study aimed to investigate the relationship between patient satisfaction of outcomes and tooth color changes during and after tooth bleaching. METHODS: In this clinical trial, 63 volunteers participated in an in-office bleaching procedure using a 40% hydrogen peroxide gel. The treatment consisted of two sessions, each comprising two 30-min applications of the bleaching gel. The L*, a*, and b* values of six maxillary anterior teeth were measured at baseline (T1), after the first bleaching session (T2), after the second bleaching session (T3), 1 week after the second in-office bleaching session (T4), and 3 weeks after the second in-office bleaching session (T5). The color differences (ΔE00 ) were calculated using CIEDE2000. A satisfaction scale with a score ranging from 0 to 3 was used to record participants' level of satisfaction with their tooth color at each time point. The data were statistically analyzed using repeated measures analysis of variance and logistic regression (α = 0.05). RESULTS: Significant correlations were observed between ΔL*, Δb*, and ΔE00 values at T3 and patient satisfaction (all p < 0.05). The regression model indicated a more pronounced impact of Δb* on patient satisfaction compared to ΔL*. The established regression models were as follows: Logit (PL*b* ) = -4.354 + 0.271ΔL* - 0.585Δb* and Logit (PΔE00 ) = -2.552 + 0.521ΔE00 . The findings suggested a minimum ΔE00 value of 4.90 for satisfactory results. A minimum ΔE00 value of 3.9, 5.0, and 6.8 was necessary for central incisors, lateral incisors, and canines, respectively, to achieve a satisfactory result. CONCLUSIONS: The ΔL*, Δb*, and ΔE00 values were found to be significantly correlated with patient satisfaction after bleaching. Δb* was identified as having a greater influence on patient satisfaction than ΔL* values in the regression model. Furthermore, attaining a minimum ΔE00 value of 4.90 is necessary to achieve satisfactory outcomes. A greater ΔE00 value is needed for canines than for incisors to achieve equivalent patient satisfaction. CLINICAL SIGNIFICANCE: This study emphasizes the importance of considering the extent of color change needed to achieve patient satisfaction after tooth bleaching procedures.


Assuntos
Clareadores Dentários , Clareamento Dental , Dente , Humanos , Cor , Peróxido de Hidrogênio , Incisivo , Satisfação do Paciente , Clareamento Dental/métodos
9.
Heliyon ; 10(3): e25827, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38352741

RESUMO

Objective: To investigate the difference and distribution of bone depth at different three-dimensional simulated paths to help optimize the insertion path for miniscrew placement in the infrazygomatic crest. Methods: Cone beam computed tomography scans of 80 adults (38 males and 42 females; mean age, 27.0 years) were assessed. For each subject, bone depth of 81 simulated insertion paths at different insertion points and three-dimensional angulations was measured in 160 infrazygomatic crests; the differences were evaluated using the adjusted Friedman test. The bone deficiency ratio for each path was calculated. Distributions of measurements were analyzed and reported as specially designed colormaps. Results: Bone depth increased, and bone deficiency ratio reduced mesially to distally (P < 0.001), apically to coronally (P < 0.01), and at a greater gingival and distal inclination (P < 0.05). The maximum bone depth (10.72 mm) was observed 13 mm above the maxillary occlusal plane in the mesiobuccal root of the maxillary second molar. The minimum bone depth (3.4 mm) was observed 17 mm above the maxillary occlusal plane in the distobuccal root of the maxillary first molar. No bone deficiency was detected at the paths of 13 mm above the maxillary occlusal plane at a gingival inclination of 70° and distal inclination of 30° in the mesiobuccal root of the maxillary second molar. The highest bone deficiency ratio is present 17 mm above the maxillary occlusal plane at a gingival inclination of 60° and a distal inclination of 0° in the distobuccal root of the maxillary first molar (89/160). Conclusion: Insertion paths located at 13 mm above the maxillary occlusal plane in the mesiobuccal root of the maxillary second molar were optimal. A gingival inclination of 70° and a distal inclination of 30° could be beneficial. The distobuccal root of the maxillary first molar region or above the 17 mm insertion plane may not be recommended.

10.
FASEB J ; 38(1): e23390, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-38169064

RESUMO

Lymph node metastasis (LNM) is one of the common features of oral tongue squamous cell carcinoma (OTSCC). LNM is also taken as a sign of advanced OTSCC and poor survival rate. Recently, single-cell RNA sequencing has been applied in investigating the heterogeneity of tumor microenvironment and discovering the potential biomarkers for helping the diagnosis and prognosticating. Pathogenesis of LNM in OTSCC remains unknown. Specifically, cancer-associated fibroblasts (CAFs) and epithelial tumor cells could foster the progression of tumors. Thus, in this study, we aimed to comprehensively analyze the roles of subpopulations of CAFs and epithelial tumor cells in lymph node metastatic OTSCC using the integration of OTSCC single-cell RNA sequencing datasets. Four distinct subtypes of CAFs, namely vascular CAFs, myofibroblast CAFs, inflammatory CAFs, and growth arrest CAFs were successfully discovered in LNM tumor and confirmed the roles of GAS and PTN pathways in the progression of tumor metastasis. In addition, NKAIN2+ epithelial cells and FN1+ epithelial cells specifically exhibited an upregulation of PTN, NRG, MIF, and SPP1 signaling pathways in the metastatic OTSCC. In doing so, we put forth some potential biomarkers that could be utilized for the purpose of diagnosing and prognosticating OTSCC during its metastatic phase and tried to confirm by immunofluorescence assays.


Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias da Língua , Humanos , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Neoplasias da Língua/genética , Neoplasias da Língua/patologia , Fibroblastos/patologia , Células Epiteliais/patologia , Biomarcadores , Metástase Linfática/patologia , Neoplasias de Cabeça e Pescoço/patologia , Análise de Sequência de RNA , Microambiente Tumoral
11.
J Infect Chemother ; 30(6): 544-547, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37992864

RESUMO

Streptococcus suis is a pathogen of emerging zoonotic diseases and meningoencephalitis is the most frequent clinical symptom of S. suis infection in humans. Rapid diagnosis of S. suis meningoencephalitis is critical for the treatment of the disease. While the current routine microbiological tests including bacterial culture and gram staining are poorly sensitive, diagnosis of S. suis meningoencephalitis by metagenomic next-generation sequencing (mNGS) has been rarely reported. Here, we report a 52-year-old female pork food producer with a broken finger developed S. suis meningoencephalitis. After her admission, no pathogenic bacteria were detected through bacterial culture and Gram staining microscopy in the cerebrospinal fluid obtained via lumbar puncture. However, mNGS identified the presence of S. suis in the sample. mNGS is a promising diagnostic tool for rapid diagnosis of rare infectious diseases in the central nervous system.

13.
Microbiol Spectr ; 12(1): e0224623, 2024 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-38047697

RESUMO

IMPORTANCE: Tuberculous meningitis is a life-threatening infection with high mortality and disability rates. Current diagnostic methods using cerebrospinal fluid (CSF) samples have limited sensitivity and lack predictive biomarkers for evaluating prognosis. This study's findings reveal excessive activation of the immune response during tuberculous meningitis (TBM) infection. Notably, a strong negative correlation was observed between CSF levels of monokine induced by interferon-γ (MIG) and the CSF/blood glucose ratio in TBM patients. MIG also exhibited the highest area under the curve with high sensitivity and specificity. This study suggests that MIG may serve as a novel biomarker for differentiating TBM infection in CSF or serum, potentially leading to improved diagnostic accuracy and better patient outcomes.


Assuntos
Tuberculose Meníngea , Humanos , Tuberculose Meníngea/diagnóstico , Tuberculose Meníngea/tratamento farmacológico , Curva ROC , Interferon gama , Soro , Biomarcadores , Líquido Cefalorraquidiano
14.
J Oral Rehabil ; 51(5): 886-897, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38151884

RESUMO

BACKGROUND: Botulinum toxin type A (BTX-A) is increasingly used to manage painful temporomandibular disorders (TMD). However, the effect of BTX-A on muscular TMD remains unclear. OBJECTIVE: To assess the efficacy, safety and optimal dose of BTX-A for treating TMD. METHODS: We conducted systematic literature searches in MEDLINE, Embase, Web of Science, ClinicalTrials.gov and Cochrane Library until March 2023. We extracted data from randomized controlled trials (RCTs) that evaluated the efficacy and safety of BTX-A in treating muscular TMD. We performed a meta-analysis using a random-effects model. RESULTS: Fifteen RCTs involving 504 participants met the inclusion criteria. BTX-A was significantly more effective than placebo in reducing pain intensity, as measured on a 0-10 scale, at 1 month (MD [95% CI] = -1.92 [-2.87, -0.98], p < .0001) and 6 months (MD [95% CI] -2.08, [-3.19 to -0.98]; p = .0002). A higher dosage of BTX-A (60-100 U bilaterally) was associated with a greater reduction in pain at 6 months (MD [95% CI] = -2.98 [-3.52, -2.44]; p < .001). BTX-A also resulted in decreased masseter muscle intensity (µV) (MD [95% CI] = -44.43 [-71.33, -17.53]; p = .001) at 1 month and occlusal force (kg) at 3 months (MD [95% CI] = -30.29 [-48.22 to -12.37]; p = .0009). There was no significant difference in adverse events between BTX-A and placebo. CONCLUSIONS: BTX-A is a safe and effective treatment for reducing pain and improving temporomandibular muscle and joint function in muscular TMD patients. A bilateral dose of 60-100 U might be an optimal choice for treating muscular TMD pain.


Assuntos
Toxinas Botulínicas Tipo A , Transtornos da Articulação Temporomandibular , Humanos , Toxinas Botulínicas Tipo A/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Dor/tratamento farmacológico , Transtornos da Articulação Temporomandibular/tratamento farmacológico , Resultado do Tratamento
15.
Ophthalmic Physiol Opt ; 44(2): 388-398, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38131130

RESUMO

PURPOSE: (1) To assess the feasibility of conducting tablet-based vision tests in hospital clinic waiting areas; (2) To test the hypothesis that increasing severity of diabetic macular oedema (DME) is associated with the performance of tablet-based surrogates of everyday tasks and self-reported visual function. METHODS: Sixty-one people with mild (n = 28), moderate (n = 24) or severe (n = 9) DME performed two tablet-based tests of 'real-world' visual function (visual search and face recognition) while waiting for appointments in a hospital outpatient clinic. Participants also completed a tablet-based version of a seven-item, visual-functioning (VF-7) patient-reported outcome measure. Test performance was compared to previously published 99% normative limits for normally sighted individuals. RESULTS: Thirty-four participants (56%; 95% confidence interval [CI] 43%-68%) exceeded normative limits for visual search, while eight (13%; 95% CI 65%-24%) exceeded normative limits for face discrimination. Search duration was significantly longer for people with severe DME than those with mild and moderate DME (p = 0.01). Face discrimination performance was not significantly associated with DME severity. VF-7 scores were statistically similar across DME severity groups. Median time to complete all elements (eligibility screening, both tablet-based tasks and the VF-7) was 22 (quartiles 19, 25) min. Further, 98% and 87% of participants, respectively, reported the search task and face discrimination task to be enjoyable, while 25% and 97%, respectively, reported finding the two tasks to be difficult. CONCLUSIONS: Portable tablet-based tests are quick, acceptable to patients and feasible to be performed in a clinic waiting area with minimal supervision. They have the potential to be piloted in patients' homes for self-monitoring.


Assuntos
Diabetes Mellitus , Retinopatia Diabética , Edema Macular , Humanos , Edema Macular/complicações , Estudos de Viabilidade , Acuidade Visual , Testes Visuais
16.
J Ethnopharmacol ; 319(Pt 3): 117253, 2024 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-37778522

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Rhizoma Drynariae, as the dried rhizome of Drynaria fortunei (Kunze ex Mett.) J. Sm., is a traditional Chinese medicine for treating the injury and bone broken of falling and beating. Total flavonoids is considered as the major and effective compounds for the therapeutic efficacy of Rhizoma Drynariae. AIM OF THE STUDY: To explore the effect of total flavonoids from Rhizoma Drynariae (TFRD) on bone regeneration and the underlying mechanisms. MATERIALS AND METHODS: The effect of TFRD in various doses on bone reconstruction in cranial bone defect rats was explored in vivo. The active ingredients in TFRD-medicated serum were characterized by serum pharmacochemistry and integrated by network pharmacology analysis and target prediction. To elucidate the underlying mechanism of TFRD on bone regeneration, experimental validation in vitro was executed to assess the influence of different concentrations of TFRD-medicated serum on osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). RESULTS: Micro-CT, histological examination, immunohistochemical analysis, and ELSA demonstrated that administration of TFRD could promote bone reconstruction in a rat cranial defect model. We identified 27 active components of TFRD using ultra-high-performance liquid chromatography coupled with tandem mass spectrometry (UHPLC-MS/MS). Results from CCK8, ALP, and Alizarin Red S staining revealed that TFRD-medicated serum notably enhanced BMSCs proliferation and osteogenic differentiation. qRT-PCR and Western blot harvested results consistent with those predicted by network pharmacology, providing further evidence that TFRD activated the TGF-ß signaling pathway to benefit bone regeneration. CONCLUSION: The active components of TFRD modulate the TGF-ß signaling pathway to facilitate osteogenesis, thereby repairing cranial bone defects.


Assuntos
Osteogênese , Polypodiaceae , Animais , Ratos , Farmacologia em Rede , Rizoma , Espectrometria de Massas em Tandem , Regeneração Óssea , Flavonoides/farmacologia , Flavonoides/uso terapêutico , Fator de Crescimento Transformador beta
17.
J Neuroinflammation ; 20(1): 277, 2023 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-38001534

RESUMO

Luteolin is a flavonoid found in high concentrations in celery and green pepper, and acts as a neuroprotectant. PSMC5 (proteasome 26S subunit, ATPase 5) protein levels were reduced after luteolin stimulation in activated microglia. We aimed to determine whether regulating PSMC5 expression could inhibit neuroinflammation, and investigate the underlying mechanisms.BV2 microglia were transfected with siRNA PSMC5 before the addition of LPS (lipopolysaccharide, 1.0 µg/ml) for 24 h in serum free DMEM. A mouse model of LPS-induced cognitive and motor impairment was established to evaluate the neuroprotective effects of shRNA PSMC5. Intracerebroventricular administration of shRNA PSMC5 was commenced 7 days prior to i.p. injection of LPS (750 µg/kg). Treatments and behavioral experiments were performed once daily for 7 consecutive days. Behavioral tests and pathological/biochemical assays were performed to evaluate LPS-induced hippocampal damage. Molecular dynamics simulation was used to confirm the interaction between PSMC5 and TLR4 (Toll-like receptor 4) in LPS-stimulated BV2 microglia. SiRNA PSMC5 inhibited BV2 microglial activation, and suppressed the release of inflammatory factors (IL-1ß, COX-2, PGE2, TNF-α, and iNOS) upon after LPS stimulation in BV2 microglia. LPS increased IκB-α and p65 phosphorylation, which was attenuated by siRNA PSMC5. Behavioral tests and pathological/biochemical assays showed that shRNA PSMC5 attenuated LPS-induced cognitive and motor impairments, and restored synaptic ultrastructure and protein levels in mice. ShRNA PSMC5 reduced pro-inflammatory cytokine (TNF-α, IL-1ß, PGE2, and NO) levels in the serum and brain, and relevant protein factors (iNOS and COX-2) in the brain. Furthermore, shRNA PSMC5 upregulated the anti-inflammatory mediators interleukin IL-4 and IL-10 in the serum and brain, and promoted a pro-inflammation-to-anti-inflammation phenotype shift in microglial polarization. Mechanistically, shRNA PSMC5 significantly alleviated LPS-induced TLR4 expression. The polarization of LPS-induced microglial pro-inflammation phenotype was abolished by TLR4 inhibitor and in the TLR-4-/- mouse, as in shRNA PSMC5 treatment. PSMC5 interacted with TLR4 via the amino sites Glu284, Met139, Leu127, and Phe283. PSMC5 site mutations attenuated neuroinflammation and reduced pro-inflammatory factors by reducing TLR4-related effects, thereby reducing TLR4-mediated MyD88 (myeloid differentiation factor 88)-dependent activation of NF-κB. PSMC5 could be an important therapeutic target for treatment of neurodegenerative diseases involving neuroinflammation-associated cognitive deficits and motor impairments induced by microglial activation.


Assuntos
Transtornos Motores , Transdução de Sinais , Animais , Camundongos , Cognição , Ciclo-Oxigenase 2/metabolismo , Inflamação/metabolismo , Lipopolissacarídeos/efeitos adversos , Luteolina/farmacologia , Microglia/metabolismo , Doenças Neuroinflamatórias , NF-kappa B/metabolismo , RNA Interferente Pequeno/metabolismo , Receptor 4 Toll-Like/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
18.
Microbiol Resour Announc ; 12(12): e0101123, 2023 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-37971261

RESUMO

In this study, we report a draft genome sequence of the endolichenic fungus Dothichiza sp. strain YAFEF048, isolated from the lichen Usnea longissima on Haba Snow Mountain. The genome resource will support future research into the endolichenic lifestyle and potential secondary metabolite diversity of this fungus.

19.
Mycobiology ; 51(5): 360-371, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37929012

RESUMO

Hispidin is an important styrylpyrone produced by Sanghuangporus sanghuang. To analyze hispidin biosynthesis in S. sanghuang, the transcriptomes of hispidin-producing and non-producing S. sanghuang were determined by Illumina sequencing. Five PKSs were identified using genome annotation. Comparative analysis with the reference transcriptome showed that two PKSs (ShPKS3 and ShPKS4) had low expression levels in four types of media. The gene expression pattern of only ShPKS1 was consistent with the yield variation of hispidin. The combined analyses of gene expression with qPCR and hispidin detection by liquid chromatography-mass spectrometry coupled with ion-trap and time-of-flight technologies (LCMS-IT-TOF) showed that ShPKS1 was involved in hispidin biosynthesis in S. sanghuang. ShPKS1 is a partially reducing PKS gene with extra AMP and ACP domains before the KS domain. The domain architecture of ShPKS1 was AMP-ACP-KS-AT-DH-KR-ACP-ACP. Phylogenetic analysis shows that ShPKS1 and other PKS genes from Hymenochaetaceae form a unique monophyletic clade closely related to the clade containing Agaricales hispidin synthase. Taken together, our data indicate that ShPKS1 is a novel PKS of S. sanghuang involved in hispidin biosynthesis.

20.
Yi Chuan ; 45(9): 793-800, 2023 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-37731233

RESUMO

Flowering represents the transition from vegetative stage to reproductive stage. As a photoperiod- sensitive crop, soybean can perceive changes in photoperiod to regulate flowering and reproductive periods, thereby influencing soybean yield and other agronomic traits, and determining the photoperiodic adaptability. Therefore, understanding the regulatory mechanisms of photoperiod on flowering and reproductive periods in soybean is one of the hotspots in soybean research. In this review, we introduce the molecular mechanisms of early flowering and early maturation during soybean domestication, and the molecular regulatory pathways of cultivated soybean expansion from the origin to high and low latitudes, respectively. At last, we summarize the research progress on photoperiod adaptability in wild soybean. Analyzing the regulatory mechanisms of photoperiod on soybean life history and domestication will provide valuable insights for the breeding of superior soybean varieties.


Assuntos
Glycine max , Fotoperíodo , Glycine max/genética , Melhoramento Vegetal , Agricultura , Domesticação
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