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1.
Artigo em Inglês | MEDLINE | ID: mdl-36633739

RESUMO

Industrial structure low-carbon restructuring is an essential channel to accelerate China's economic growth and fulfilling carbon emission reduction goals. Whether carbon emission trading pilot policy, as an influential carbon reduction instrument, fosters industrial structure low-carbon restructuring is of major significance to green economic development. This paper empirically investigates the shock of the carbon emission trading pilot policy on industrial structure low-carbon restructuring using the differences-in-differences (DID) and synthetic control method (SCM). Statistics reveal that sectors with low carbon productivity, such as electricity, steam, and hot water production and supply, ferrous metal smelting and pressing, etc., and sectors with high carbon productivity, such as electrical equipment and machinery, electronics and telecommunication equipment, etc. The industrial structure did not develop a stable trend of change before the 12th Five-Year Plan, but a stable trend of low-carbon restructuring emerged after such a period. Carbon emission trading pilot policy significantly facilitates industrial structural low-carbon restructuring. Carbon emission trading pilot policy inhibits energy-intensive industries in the industrial sector significantly, which promotes industrial structure low-carbon restructuring. Therefore, policymakers need to develop a nationwide carbon emission trading market that includes more industries to guide production factors to industrial sectors with high carbon productivity for industrial restructuring and dual carbon goals.

2.
iScience ; 26(1): 105736, 2023 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-36570769

RESUMO

Influenza A virus poses a constant challenge to human health. The highly conserved influenza matrix-2 (M2) protein is an attractive target for the development of a universal antibody-based drug. However, screening using antigens with subphysiological conformation in a nonmembrane environment significantly reduces the generation of efficient antibodies. Here, M2(1-46) was incorporated into nanodiscs (M2-nanodiscs) with M2 in a membrane-embedded tetrameric conformation, closely resembling its natural physiological state in the influenza viral envelope. M2-nanodisc generation, an antigen, was followed by Chiloscyllium plagiosum immunization. The functional vNARs were selected by phage display panning strategy from the shark immune library. One of the isolated vNARs, AM2H10, could specifically bind to tetrameric M2 instead of monomeric M2e (the ectodomain of M2 protein). Furthermore, AM2H10 blocked ion influx through amantadine-sensitive and resistant M2 channels. Our findings indicated the possibility of developing functional shark nanobodies against various influenza viruses by targeting the M2 protein.

3.
Front Microbiol ; 13: 977382, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36406407

RESUMO

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease, which is caused by severe fever with thrombocytopenia syndrome virus (SFTSV). The disease results in high mortality and increased morbidity and threatens global public health. Rapid detection of SFTSV is crucial for epidemic prevention in low-resource settings. Here we developed deployable, sensitive and rapid detection methods based on CRISPR/Cas12a or Cas13a technologies. The CRISPR/Cas12a-based detection assay could stably detect the SFTSV L or M genes at 10 cp/µl. The Cas13a-based method could detect the L gene as low as 0.75 cp/µl. For point-of-care testing, we combined fluorescence visualization and lateral flow detection with CRISPR/Cas-based assays. Furthermore, using the orthogonal DNA/RNA collateral activity of the Cas12a/Cas13a system, we present the dual-gene detection platform for SFTSV, which can simultaneously detect the L and M genes in a single tube. Based on the dual-gene detection, we designed multiplexed test strips to detect SFTSV. All our methods were initially validated using 52 clinical samples, showing 100% sensitivity and specificity. These new CRISPR/Cas-based detection methods are promising candidates for on-site detection of SFTSV.

4.
Front Cardiovasc Med ; 9: 922335, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36386331

RESUMO

Dysfunction of potassium voltage-gated channel subfamily Q member 1 (KCNQ1) is a primary cause of long QT syndrome type 1 (LQT1). Here, we report a missense mutation P441L in KCNQ1 C-terminus of a 37-year-old woman with severe LQT1 phenotype. Variant P441L transporting to the plasma membrane and interacting with KCNE1 were both markedly decreased, leading to potassium efflux disorder and eventually LQT1. Mutations between the C-terminal helix A and helix B of KCNQ1 have linked with low cardiac event risk, however, we firstly find variant P441L causing a severe LQT1 phenotype with a high risk of cardiac events.

5.
Int J Chron Obstruct Pulmon Dis ; 17: 2871-2891, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36411774

RESUMO

Purpose: As a common respiratory disease, chronic obstructive pulmonary disease (COPD) has a high morbidity and mortality. Current clinical therapies are not ideal and do not improve lung function or long-term life quality. It is very important to find new potential pathogenic mechanisms, biomarkers, and targets with therapeutic value in COPD. Methods: Serum samples collected from acute exacerbation and stable COPD and healthy participants were analyzed using label-free liquid chromatography tandem mass spectrometry to identify the differentially expressed proteins (DEPs) between two groups. Bioinformatics analyses were performed to determine the biological processes associated with those DEPs. Key proteins were validated by enzyme linked immunosorbent assay (ELISA). Results: In total, 661 proteins were detected in serum from patients with COPD and healthy participants. Compared with healthy participants, patients with acute exacerbation of COPD had 45 DEPs, 13 were upregulated and 32 were downregulated; and patients with stable COPD had 79 DEPs, 18 were upregulated and 61 were downregulated. Gene Ontology functional annotation results indicated that the DEPs identified in patients with COPD were associated with the terms cellular anatomical entity, binding, and cellular process. Kyoto Encyclopedia of Genes and Genomes functional annotation analysis and the Clusters of Orthologous Genes database analysis indicated that the functions of these DEPs were primarily in signal transduction mechanisms and amino acid transport and metabolism. The ELISA results for three key proteins of IGFBP2, LRG1 and TAGLN were consistent with the LC-MS/MS results and the area under the receiver operating characteristic of the combined index was 0.893 (95% CI: 0.813, 0.974). Conclusion: Our findings suggested pathogenic mechanisms underlying COPD stages and indicated three key proteins that may warrant further study as potential biomarkers for early diagnosis or prognosis of COPD or as therapeutic targets.


Assuntos
Proteômica , Doença Pulmonar Obstrutiva Crônica , Humanos , Proteômica/métodos , Biologia Computacional , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/genética , Cromatografia Líquida , Espectrometria de Massas em Tandem , Proteínas Sanguíneas , Biomarcadores
6.
World J Diabetes ; 13(11): 962-971, 2022 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-36437862

RESUMO

The adverse consequences resulting from diabetes are often presented as severe complications. Diabetic wounds are one of the most commonly occurring complications in diabetes, and the control and treatment of this is costly. Due to a series of pathophysiological mechanisms, diabetic wounds remain in the inflammatory phase for a prolonged period of time, and face difficulty in entering the proliferative phase, thus leading to chronic non-healing wounds. The current consensus on the treatment of diabetic wounds is through multidisciplinary comprehensive management, however, standard wound treatment methods are still limited and therefore, more effective methods are required. In recent years, defensins have been found to play diverse roles in a variety of diseases; however, the molecular mechanisms underlying these activities are still largely unknown. Defensins can be constitutively or inductively produced in the skin, therefore, their local distribution is affected by the microenvironment of these diabetic wounds. Current evidence suggests that defensins are involved in the diabetic wound pathogenesis, and can potentially promote the early completion of each stage, thus making research on defensins a promising area for developing novel treatments for diabetic wounds. In this review, we describe the complex function of human defensins in the development of diabetic wounds, and suggest potential thera-peutic benefits.

7.
Arch Sex Behav ; 2022 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-36253559

RESUMO

Gender-affirming surgery (GAS) is often sought after to alleviate the distress of those who suffer from gender dysphoria (GD). While many studies have shown that a significant percentage of people benefit from this procedure, a number of individuals later regret their decision of undergoing surgery. Studies have illustrated what regret depicts, categorizing regret based on intensity, persistency, and sources, in the hopes to prevent an unwanted irreversible intervention. Here, an in-depth interview with a 35-year-old transwoman from Taiwan who underwent feminizing GAS at the age of 31 illustrates her unique cultural upbringing and the course of her regret. Her experience best matches the characteristics of true regret and major regret based on the classifications of Pfäfflin and Wiepjes, respectively, indicating that she expected GAS to be the solution to her personal acceptance issue, but, in retrospect, regretted the diagnosis and treatment as her problems were not solved and worsened to the extent of secondary dysphoria. This case report hopes to shed light on the complexity of GD and regret after GAS, while encouraging the pre-surgical evaluation of psychological comorbidities and post-surgical psychotherapy, and ensuring that patients are informed and give full consent. In addition, more elaborate, long-term, large-scale qualitative research, especially within more conservative cultural settings, is needed.

8.
Biomed Pharmacother ; 156: 113807, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36242850

RESUMO

Since the end of 2019, the outbreak of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has triggered a pneumonia epidemic, posing a significant public health challenge in 236 countries, territories, and regions worldwide. Clinically, in addition to the symptoms of pulmonary infection, many patients with SARS-CoV-2 infections, especially those with a critical illness, eventually develop multiple organ failure in which damage to the kidney function is common, ultimately leading to severe consequences such as increased mortality and morbidity. To date, three coronaviruses have set off major global public health security incidents: Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV), Middle East Respiratory Syndrome Coronavirus (MERS-CoV), and SARS-CoV-2. Among the diseases caused by the coronaviruses, the coronavirus disease 2019 (COVID-19) has been the most impactful and harmful. Similar to with SARS-CoV-2 infections, previous studies have shown that kidney injury is also common and prominent in patients with the two other highly pathogenic coronaviruses. Therefore, in this review, we aimed to comprehensively summarize the epidemiological and clinical characteristics of these three pandemic-level infections, provide a deep analysis of the potential mechanism of COVID-19 in various types of kidney diseases, and explore the causes of secondary kidney diseases of SARS-CoV-2, so as to provide a reference for further research and the clinical prevention of kidney damage caused by coronaviruses.


Assuntos
COVID-19 , Coronavírus da Síndrome Respiratória do Oriente Médio , Humanos , SARS-CoV-2 , Pandemias , Rim
9.
Front Pharmacol ; 13: 980930, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36249739

RESUMO

The incidence rate of acute pancreatitis is increasing, and severe acute pancreatitis (SAP) is associated with a high mortality rate, which may be reduced by a deeper understanding of its pathogenesis. In addition, an early determination of the severity of acute pancreatitis remains challenging. The aim of this study was to match potential biomarkers for early identification and monitoring of acute pancreatitis and to shed light on the underlying pathogenic mechanisms of SAP. The expression levels of plasma exosomal microRNA (miRNA) in patients with pancreatitis have been associated with the disease. Thus, this study compared the expression levels of exosomal miRNA in plasma collected from four patients with SAP and from four healthy participants. Analyses of the miRNA expression profiles indicated that three previously unreported miRNAs were differentially expressed in the patient group: Novel1, which was downregulated, and Novel2 and Novel3, which were upregulated. The miRNA target genes for those novel miRNAs were predicted using Metascape. Of these miRNA target genes, those that were also differentially expressed at different time points after disease induction in a mouse model of acute pancreatitis were determined. The gene for complement component 3 (C3), a target gene of Novel3, was the only gene matched in both the patient group and the mouse model. C3 appeared at most of the time points assessed after induction of acute pancreatitis in mice. These findings are foundational evidence that C3 warrants further study as an early biomarker of SAP, for investigating underlying pathogenic mechanisms of SAP, and as a therapeutic target for ameliorating the occurrence or development of SAP.

10.
J Sex Med ; 19(10): 1517-1523, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36057523

RESUMO

BACKGROUND: Vaginal lubrication and contractions are among the top difficulties affecting sexual intercourse in women after spinal cord injury. AIM: This study aimed at determining if pudendal nerve stimulation (PNS) can improve vaginal lubrication and induce increases in vaginal pressure. METHODS: In anesthetized cats, a small piece of cotton was inserted into the vagina for 10 minutes with or without PNS to measure vaginal wetness by the weight increase of the vaginal cotton. Then, a small balloon catheter was inserted into the vagina to measure the pressure increase induced by PNS. Intensity response of the vagina to PNS (30 Hz, 0.2 ms, 5 seconds) was determined at 1-4 times of intensity threshold (T) for PNS to induce an observable vaginal pressure increase. Frequency response was determined at 2T intensity in a range of PNS frequencies (5-50 Hz). Finally, fatigue in vaginal pressure was determined by applying PNS (30 Hz, 2T) either continuously or intermittently (5 seconds on and 5 seconds off) for 4 minutes. OUTCOMES: The effectiveness of PNS in increasing vaginal wetness and pressure is evaluated. RESULTS: PNS significantly (P = .0327) increased the measurement of vaginal wetness from 15.8 ± 3.8 mg during control without stimulation to 32.4 ± 4.7 mg after stimulation. Vaginal pressure increased as PNS intensity or frequency increased. PNS (30 Hz, 2T) induced vaginal pressure increase ≥80% of the maximal response. Intermittent PNS induced significantly (P = .0354) smaller fatigue (45.6 ± 3.7%) in vaginal pressure than continuous PNS (69.1 ± 3.0%) during the 4-minute stimulation. CLINICAL TRANSLATION: This study raises the possibility of developing a novel pudendal neuromodulation device to improve female sexual function after spinal cord injury. STRENGTHS & LIMITATIONS: This study provides preclinical data supporting the development of a novel pudendal neuromodulation device. The limitation includes the lack of chemical analysis of the vaginal secretion. CONCLUSION: PNS can improve vaginal lubrication and induce increases in vaginal pressure. Chen J, Zhong Y, Wang J, et al. Vaginal Lubrication and Pressure Increase Induced by Pudendal Nerve Stimulation in Cats. J Sex Med 2022;19:1517-1523.


Assuntos
Nervo Pudendo , Vagina , Animais , Gatos , Estimulação Elétrica , Feminino , Lubrificação , Fadiga Muscular , Pressão , Nervo Pudendo/fisiologia , Vagina/fisiologia
11.
BMC Urol ; 22(1): 142, 2022 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-36057655

RESUMO

BACKGROUND: Bladder cancer (BC) is one of the most common malignancies of the genitourinary system. Animal models offer an important tool to explore tumour initiation, progression, and therapeutic mechanisms. Our aim is to construct an optimized orthotopic BC model which is predictable, reproducible, and convenient. METHODS: The optimized orthotopic BC model was constructed in male C57BL/6 mice utilizing microsyringes to inoculate them with a murine BC cell line (MB49). Anesthetised mice were inoculated with an MB49 cell suspension (10 µL) at approximately 5 × 106/mL. The whole process of modelling was observed and monitored every 3 days for 21 days utilizing HE staining and transabdominal ultrasonography (TUS). RESULTS: In this study, the model showed excellent success rates for tumour formation (96.67%) and metastatic rate (89.66%). Compared to the control group (sham operation), mice in the modelling group had serous cachexia, visible haematuresis and weight loss (all P < 0.05). The lungs, liver, ureter and kidneys were found to have tumour metastasis. Moreover, the average survival time (19.73 ± 1.69 d) of modelling mice was significantly shorter than that of the control mice (P < 0.05), which remained alive. CONCLUSION: Our study established a method using microsyringes to inject murine BC cells into the bladder wall, creating a stable transplantable BC model in mice.


Assuntos
Neoplasias da Bexiga Urinária , Animais , Linhagem Celular Tumoral , Modelos Animais de Doenças , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/patologia
13.
Neuromodulation ; 2022 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-35941016

RESUMO

OBJECTIVE: This study aimed at determining whether stimulation of sacral spinal roots can induce penile erection in cats. MATERIALS AND METHODS: In anesthetized cats, a 20-gauge catheter was inserted into the corpus cavernosum to measure the penile pressure. Stimulus pulses (5-80 Hz, 0.2 ms) were applied through bipolar hook electrodes to sacral ventral roots alone or to combined ventral and dorsal roots of a single S1-S3 segment to induce penile pressure increases and penile erection. RESULTS: Stimulation of the S1 or S2 ventral root at 30 to 40 Hz induced observable penile erection with rigidity and the largest increase (169 ± 11 cmH2O) in penile pressure. Continuous stimulation (10 minutes) of afferent and efferent axons by simultaneous stimulation of the S1 or S2 dorsal and ventral roots at 30 Hz also produced a large increase (190 ± 8 cmH2O) in penile pressure that was sustainable during the entire stimulation period. After a complete spinal cord transection at the T9-T10 level, simultaneous stimulation of the S1 or S2 dorsal and ventral roots induced large (186 ± 9 cmH2O) and sustainable increases in penile pressure. CONCLUSION: This study indicates the possibility to develop a novel neuromodulation device to restore penile erection after spinal cord injury using a minimally invasive surgical approach to insert a lead electrode through the sacral foramen to stimulate a sacral spinal root.

14.
Anal Chem ; 94(29): 10355-10366, 2022 07 26.
Artigo em Inglês | MEDLINE | ID: mdl-35830352

RESUMO

Hyperspectral images can be generated from mass spectrometry imaging (MSI) data for the intuitive data visualization purpose. However, hundreds of HSIs can be generated by different dimensionality reduction methods, which poses great challenges in selecting the high-quality images with the best intuitive visualization results of the MSI data. Here, we presented a novel approach that objectively evaluates the image quality of the hyperspectral images. The applicability of this method was demonstrated by analyzing the MSI data acquired from human prostate cancer biopsy samples and mouse brain tissue section, which harbored an intrinsic tissue heterogeneity. Our method was based on the information entropy and contrast measured from image information content and image definition, respectively. The heterogeneity of the MSI data from high-dimensional space was reduced to three-dimensional embeddings and thoroughly evaluated to achieve satisfactory visualization results. The application of information entropy and contrast can be used to choose the optimized visualization results rapidly and objectively from an extensive number of hyperspectral images and be adopted to evaluate and optimize different dimensionality reduction algorithms and their hyperparameter combinations. In conclusion, the information entropy-based strategy could be a bridge between chemometrician and biologists.


Assuntos
Algoritmos , Diagnóstico por Imagem , Animais , Entropia , Humanos , Masculino , Espectrometria de Massas/métodos , Camundongos
15.
Front Mol Biosci ; 9: 915993, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35874606

RESUMO

Primary biliary cholangitis (PBC) is an autoimmune-mediated chronic cholestatic liver disease, fatigue, and skin itching are the most common clinical symptoms. Its main pathological feature is the progressive damage and destruction of bile duct epithelial cells. Non-coding RNA (NcRNA, mainly including microRNA, long non-coding RNA and circular RNA) plays a role in the pathological and biological processes of various diseases, especially autoimmune diseases. Many validated ncRNAs are expected to be biomarkers for the diagnosis or treatment of PBC. This review will elucidate the pathogenesis of PBC and help to identify potential ncRNA biomarkers for PBC.

16.
Clin Respir J ; 16(8): 546-554, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35866671

RESUMO

Natural killer (NK) cells are regarded as the host's first line of defense against viral infection. Moreover, the involvement of NK cells in chronic obstructive pulmonary disease (COPD) has been documented. However, the specific mechanism and biological changes of NK cells in COPD development have not been determined. In this study, we extracted NK cells from the peripheral blood of 18 COPD patients who were recovering from an acute exacerbation and 45 healthy donors (HDs), then we labeled NK cells with different antibodies and analyzed with flow cytometry. The data showed that the frequencies of total NK cells in the peripheral blood of COPD patients were lower compared with HDs. Moreover, the inhibitory receptors on NK cells expressed higher levels and the expression of activating receptors were generally low. Importantly, both the expression levels of CD96 in NK cells and the frequencies of CD96+ NK cells were significantly upregulated in COPD patients. These findings suggest that surface receptor CD96 from NK cells may be a risk factor in the evolution of COPD.


Assuntos
Células Matadoras Naturais , Doença Pulmonar Obstrutiva Crônica , Antígenos CD/metabolismo , Citometria de Fluxo , Humanos , Células Matadoras Naturais/metabolismo
17.
J Transl Med ; 20(1): 315, 2022 07 14.
Artigo em Inglês | MEDLINE | ID: mdl-35836227

RESUMO

BACKGROUND: Enolase is an essential enzyme in the process of glycolysis and has been implicated in cancer progression. Though dysregulation of ENOs has been reported in multiple cancers, their prognostic value and specific role in bladder cancer (BLCA) remain unclear. METHODS: Multiple databases were employed to examine the expression of ENOs in BLCA. The expression of ENO1 was also validated in BLCA cell lines and tissue samples by western blotting and immunohistochemistry. Kaplan-Meier analysis, ROC curve, univariate and multivariate Cox regression were performed to evaluate the predictive capability of the ENO1. Gene ontology (GO) and Gene Set Enrichment Analyses (GSEA) analysis were employed to perform the biological processes enrichment. Function experiments were performed to explore the biological role of ENO1 in BLCA. The correlation of ENO1 with immune cell infiltration was explored by CIBERSORT. RESULTS: By analyzing three ENO isoforms in multiple databases, we identified that ENO1 was the only significantly upregulated gene in BLCA. High expression level of ENO1 was further confirmed in BLCA tissue samples. Aberrant ENO1 overexpression was associated with clinicopathological characteristics and unfavorable prognosis. Functional studies demonstrated that ENO1 depletion inhibited cancer cell aggressiveness. Furthermore, the expression level of ENO1 was correlated with the infiltration levels of immune cells and immune-related functions. CONCLUSIONS: Taken together, our results indicated that ENO1 might serve as a promising prognostic biomarker for prognosticating prognosis associated with the tumor immune microenvironment, suggesting that ENO1 could be a potential immune-related target against BLCA.


Assuntos
Neoplasias da Bexiga Urinária , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Proteínas de Ligação a DNA/genética , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Fosfopiruvato Hidratase/genética , Prognóstico , Microambiente Tumoral , Proteínas Supressoras de Tumor/genética , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/patologia
18.
Molecules ; 27(12)2022 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-35745003

RESUMO

Acute pancreatitis (AP) is a pancreatic inflammatory disease that varies greatly in course and severity. To further the understanding of the pathology of AP, we carried out data-independent acquisition-based proteomic analyses using proteins extracted from the plasma of patients with severe acute pancreatitis (SAP) (experimental group) and healthy volunteers (control group). Compared to the control group, there were 35 differentially expressed proteins (DEPs) in the plasma of patients with SAP. Of those, the expression levels for 6 proteins were significantly increased, and 29 proteins were significantly decreased. Moreover, six candidate biomarkers-VWF, ORM2, CD5L, CAT, IGLV3-10, and LTF-were matched as candidate biomarkers of the disease severity of AP. The area under the receiver operating characteristic of 0.903 (95% CI: 0.839, 0.967) indicated that this combination of these six candidate biomarkers had a good prediction accuracy for predicting the severity of AP. Our study provides specific DEPs that may be useful in the diagnosis and prognosis of SAP, which suggests new theoretical bases for the occurrence and development of SAP and offers potential novel treatment strategies for SAP.


Assuntos
Pancreatite , Doença Aguda , Biomarcadores , Proteínas Sanguíneas , Humanos , Pancreatite/diagnóstico , Proteômica , Curva ROC , Índice de Gravidade de Doença
19.
Drug Des Devel Ther ; 16: 1231-1254, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35517983

RESUMO

Purpose: This study aimed to reveal the multicomponent synergy mechanisms of SWP based on network pharmacology and metabolomics for exploring the relationships of active ingredients, biological targets, and crucial metabolic pathways. Materials: Network pharmacology, including TRRUST, GO, and KEGG, enrichment was used to discover the active ingredients and potential regulation mechanisms of SWP. LC-MS and multivariate data analysis method were further applied to analyze serum metabolomics profiling for discovering the potential metabolic mechanisms of SWP on AA induced by Cyclophosphamide (CTX) and 1-Acetyl-2-phenylhydrazine (APH). Results: A total of 27 important bioactive ingredients meeting the ADME (absorption, distribution, metabolism, and excretion) screening criteria from SWP were selected. Interaction networks were constructed and validated based on the 10 associated ingredients with the relevant targets. A total of 125 biomarkers were found by Metabolomics approach, which associated with the development of AA, mainly involved in amino acid metabolism and lipid metabolism. While SWP can reverse the above 12 metabolites changed by AA. Network analysis revealed the synergistic effects of SWP through the 43 crucial pathways, including Sphingolipid signaling pathway, Sphingolipid metabolism, Arginine and proline metabolism, VEGF signaling pathway, Estrogen signaling pathway. Conclusion: The study suggested that SWP is a useful alternative for the treatment of AA induced by CTX + APH. Its potential mechanisms are to improve hematopoietic microenvironment and promote bone marrow hematopoiesis therapies.


Assuntos
Anemia Aplástica , Medicamentos de Ervas Chinesas , Anemia Aplástica/induzido quimicamente , Anemia Aplástica/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Humanos , Metabolômica/métodos , Farmacologia em Rede , Esfingolipídeos
20.
Nat Commun ; 13(1): 2518, 2022 05 06.
Artigo em Inglês | MEDLINE | ID: mdl-35523813

RESUMO

The nervous and endocrine systems coordinate with each other to closely influence physiological and behavioural responses in animals. Here we show that WAKE (encoded by wide awake, also known as wake) modulates membrane levels of GABAA receptor Resistance to Dieldrin (Rdl), in insulin-producing cells of adult male Drosophila melanogaster. This results in changes to secretion of insulin-like peptides which is associated with changes in juvenile hormone biosynthesis in the corpus allatum, which in turn leads to a decrease in 20-hydroxyecdysone levels. A reduction in ecdysone signalling changes neural architecture and lowers the perception of the male-specific sex pheromone 11-cis-vaccenyl acetate by odorant receptor 67d olfactory neurons. These finding explain why WAKE-deficient in Drosophila elicits significant male-male courtship behaviour.


Assuntos
Proteínas de Drosophila , Insulinas , Acetatos , Animais , Corte , Drosophila/metabolismo , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/metabolismo , Sistema Endócrino/metabolismo , Masculino , Percepção , Feromônios , Receptores de GABA-A , Comportamento Sexual Animal/fisiologia
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