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1.
Surg Radiol Anat ; 2021 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-34642771

RESUMO

PURPOSE: To reveal differences in the pattern of trabecular architecture in the epiphysis and metaphysis of the proximal tibia. METHODS: The trabecular architecture of the proximal tibia was observed in 27 P45 plastinated knee specimens. RESULTS: In the medial and lateral condyles, under the articular cartilage surrounded by the medial or lateral meniscus, the cancellous bone is formed by thick and dense trabecular bands, which run longitudinally in the epiphysis and then pass through the epiphyseal line to terminate on the slanted cortex of the metaphysis. In the intercondylar eminence, the trabeculae are arranged basically in a network. In the central portion of the tibial metaphysis, cancellous bone consists of fine arcuate trabeculae, which extend to the anterior and posterior cortices, respectively. These trabeculae are intersected sparsely and form trusses over the medullary cavity. Near the areas of attachment of the iliotibial tract, tibial collateral ligament, anterior and posterior cruciate ligaments, and patellar ligament, the cancellous bone is locally reinforced with patchy trabeculae, dense radiating trabeculae, or two orthotropic trabecular bands. CONCLUSION: This study provides further accurate anatomical information on the trabeculae of the proximal tibia. The soft structures of knee joint, including the articular cartilage, menisci, and ligaments, and the slanted cortices of the metaphysis are important landmarks for the location of different arrangements of the cancellous architecture. The present results are beneficial for clinical diagnosis and treatment of pathologies of the knee joint, or the establishment of a finite element analysis model of the knee joint.

2.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 52(5): 832-838, 2021 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-34622601

RESUMO

Objective: To study the distributional characteristics of allergens in children with allergic diseases in Shaanxi province. Methods: A total of 4 622 children diagnosed with allergic diseases in the Asthma Center, Department of Pediatrics, Xijing Hospital from March 2015 to February 2019 were selected. Serum allergen-specific immunoglobulin E (sIgE) of 19 common kinds of allergens were examined with enzyme-linked immunosorbent assay (ELISA). The children were divided into different groups according to sex, age and geographical regions, and the distributional characteristics of allergens of the different groups were compared. Results: The overall positive rate for the 19 allergens of the 4 622 children was 62.8%. The ranking of the positive rates for individual allergens from high to low were as follows: 24.2% for milk, 18.0% for mold mix, 16.7% for dog dander, 16.4% for house dust mite, 11.7% for cat dander, 10.7% for cashew, 10.6% for weed pollen, 8.8% for egg white, 7.8% for house dust, 7.7% for tree pollen, 5.6% for amaranth, 4.9% for mulberry tree, 3.6% for mango, 3.2% for beef, 2.8% for cockroach, 2.1% for crab, 1.5% for shrimp, 0.8% for pineapple, and 0.3% for shellfish. Analysis based on sex showed that the allergen positive rates in boys were higher than those in girls. Analysis by age difference showed that generally the positive rates for inhaled allergens increased along with the increase in patient age, while the positive rates for ingested allergens decreased along with the increase in patient age. Analysis by geographical regions showed that the positive rate of house dust mite in the patients from the southern part of Shaanxi, the positive rate of weed pollen in the patients from the northern part of Shaanxi and the positive rates of milk and egg white in the patients from the central part of Shaanxi were higher than those in other areas. The cluster analysis and correlation analysis showed that the 19 allergens could be roughly divided into 4 categories. There were moderate correlations among tree pollen, mulberry tree and amaranth. There were moderate correlations among mulberry tree, mango and amaranth. There was moderate correlation between shrimp and crab, and there were mild or weak correlations among most of the other allergens. Conclusion: Among the 4 622 children with allergic diseases in Shaanxi Province who were treated in the Asthma Center, Department of Pediatrics, Xijing Hospital, male patients showed higher sensitivity to allergens. The positive rates of inhaled allergens increased, while the positive rates of ingested allergens decreased with increase in patient age. There were regional differences in the distribution of allergens. Some allergens were correlated with each other, which may be related to cross-reaction.


Assuntos
Asma , Hipersensibilidade , Alérgenos , Animais , Asma/epidemiologia , Gatos , Bovinos , Criança , Cães , Poeira , Humanos , Imunoglobulina E , Masculino
3.
Plant Sci ; 312: 111052, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34620447

RESUMO

Drought occurrence seriously affects the productivity and quality of apple crop worldwide. Autophagy, a conserved process for the degradation and recycling of unwanted cellular components, is considered to positively regulate the tolerance of various abiotic stresses in plants. In the current study, we isolated two ATG5 homologs genes, namely, MdATG5a and MdATG5b, from apple, demonstrating their responsiveness to drought and oxidative stresses. In addition to having the same cellular localization in the nucleus and cytoplasm, both MdATG5a and MdATG5b could interact with MdATG12. Transgenic apple plants overexpressing MdATG5a exhibited an improved drought tolerance, as indicated by less drought-related damage and higher photosynthetic capacities compared to wild-type (WT) plants under drought stress. The overexpression of MdATG5a improved antioxidant defenses in apple when exposed to drought via elevating both antioxidant enzyme activities and the levels of beneficial antioxidants. Furthermore, under drought stress, the overexpression of MdATG5a promoted the mobilization of starch to accumulate greater levels of soluble sugars, contributing to osmotic adjustments and supporting carbon skeletons for proline synthesis. Such changes in physiological responses may be associated with increased autophagic activities in the transgenic plants upon exposure to drought. Our results demonstrate that MdATG5a-mediated autophagy enhances drought tolerance of apple plants via improving antioxidant defenses and metabolic adjustments.

4.
Artigo em Inglês | MEDLINE | ID: mdl-34610440

RESUMO

BACKGROUND: Extragonadal yolk sac tumors (YSTs) occurring in the uterus are extremely rare. To report a uterine YST case in a prepubertal girl and review literature on uterine YST to outline clinical management in diagnosis and treatment. CASE: We present a case of a 2-year-old girl who presented with vaginal bleeding and a pelvic mass. The diagnosis of YST was confirmed via biopsy. After four cycles of neoadjuvant chemotherapy combined with cisplatin, etoposide, and bleomycin (PEB), vaginoscopic examination and laparoscopy revealed a uterine YST without metastasis. The patient was treated with laparoscopic hysterectomy and two cycles of PEB postoperatively. During the 18 months of follow-up, the patient remained disease-free. SUMMARY AND CONCLUSION: Primary uterine YST is extremely rare and no treatment guidelines have been established to date. Surgery combined with PEB chemotherapy is considered effective for uterine YST.

5.
Clin Lung Cancer ; 2021 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-34645582

RESUMO

BACKGROUND: Pleural effusion (PE) has been one of the promising sources of liquid biopsy in advanced lung cancer patients. However, its clinical utility is not widely accepted due to the lack of full estimation of its potential versus routine clinical samples. METHOD: A total of 164 advanced lung cancer patients were enrolled with 164 matched tumor tissue and PE-cfDNA, 153 accompanied plasma and 63 1PE-sDNA. RESULT: PE-cfDNA displayed significantly higher median mutant allele frequency and an overall mutation concordance rate of 65% to tissue, which was higher than PE-sDNA (43%) and plasma-cfDNA (43%). The discrepancies between PE-cfDNA and tumor tissue were high in several genes, including SMARCA4, PIK3CA, ERBB2, KM T2A, ALK and NF1. For clinically actionable mutations, the concordance rate between PE-cfDNA and tumor tissue is 87%. Eleven patients were identified with actionable mutations in PE-cfDNA and four patients benefited from PE-cfDNA-guided targeted. Meanwhile, PE-cfDNA recapitulated mutations of diverse tissue origins and provided more mutational information under the circumstance that tumor tissue or tumor tissue of different origins were unavailable. The combination of tumor tissue and PE-cfDNA profiling increased positive detection rates of patients compared to tumor tissue alone. Our finding highlighted the importance of PE-cfDNA in the optimal selection of patients for targeted therapy. CONCLUSION: The PE-cfDNA-based liquid biopsy displays better performance in the characterization of gene alterations than PE-sDNA and plasma-cfDNA. PE-cfDNA together with tumor tissue profiling optimizes comprehensively genomic profiling of lung cancer patients, which might be important for selecting patients for better treatment management.

6.
Appl Opt ; 60(25): 7563-7573, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34613222

RESUMO

In view of the functional requirements of high reliability and stability support of optical components of space remote sensors, a rigid-flexible, dual-mode coupling support structure for space-based rectangular curved prisms (SRCPs) was designed. In-depth studies of the support principle and engineering realization of the SRCPs and optimization of the flexible adhesive structure were performed. Static and dynamic simulations were conducted on the mirror subassembly by means of finite element analysis, and test verification was also performed. The tests revealed that the surface shape error of the mirror subassembly after mechanical testing was 0.021λ, the displacement of the mirror body was 0.008 mm, the inclination angle was ∼0.8'', the mass of the mirror subassembly was 4.79 kg, the fundamental frequency was 283 Hz, and the maximum amplification of the total rms acceleration was 4.37. All indexes were superior to those of the design requirements. On this basis, bonding tests and mechanical tests of a rectangular curved prism reflector, a rectangular curved prism, and a rectangular plane reflector employing this proposed support structure were continued. The test results verified the reliability, stability, and universal applicability of the proposed rigid-flexible, dual-mode peripheral bonding support structure.

7.
Zhongguo Zhen Jiu ; 41(10): 1171-4, 2021 Oct 12.
Artigo em Chinês | MEDLINE | ID: mdl-34628753

RESUMO

Through analyzing the indication distribution of the different acupoints located at the upper limbs recorded in Science of Acupoints and Science of Meridians and Acupoints, the industry planning teaching materials of traditional Chinese medicine, it is discovered that the acupoints located at the upper arms are commonly selected for the treatment of scrofula and goiter, while the acupoints below the elbow at the hand meridians and those at the lower limbs of the foot meridians which running through the neck, do not have the similar indications. Based on a further analysis on the literature at ancient and modern times, it is believed that the acupoints located on the lateral side of the upper arms, especially those at the large intestine meridian of hand-yangming perhaps have the specific effect in treatment of scrofula and goiter.


Assuntos
Bócio , Meridianos , Tuberculose dos Linfonodos , Pontos de Acupuntura , Braço , Humanos
9.
Cancer Nurs ; 2021 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-34483287

RESUMO

BACKGROUND: Compression therapy is a common method for treating breast cancer-related lymphedema. However, no specific evidence exists to guide practitioners on the morbidity of lymphedema, limb volume, and range of motion. OBJECTIVE: The aims of this study were to compare the effects of compression therapy and routine nursing during the treatment of breast cancer-related lymphedema and to provide a basis for better clinical decision-making. METHODS: The PubMed, Cochrane Library, EMBASE, Web of Science, CBM, CNKI, Wanfang, and VIP databases were searched through January 21, 2021. Meta-analysis and description of the outcomes were performed by using the RevMan 5.3 software. RESULTS: A total of 17 studies were included. A meta-analysis of 13 studies was conducted. The experimental group had a lower morbidity of lymphedema, the difference was significant, and there was no heterogeneity (P < .05; odds ratio, 0.35, I2 = 31%). There was no significant difference between the experimental group and control group in limb volume, and there was significant heterogeneity (P = .44, mean difference = 4.51, I2 = 85%). Regarding range of motion, the standardized mean difference of shoulder adduction, shoulder lift, shoulder abduction, and shoulder extension were 1.37, 0.69, 0.56, and 0.87, respectively, and the differences were significant; there was heterogeneity (P < .05, I2 = 92%). CONCLUSIONS: Compression therapy can reduce the morbidity of lymphedema and improve limb movement, but the effect on limb volume needs to be further explored. IMPLICATION FOR PRACTICE: In terms of therapeutic effectiveness and limb function, the results provide evidence that physicians can reduce the morbidity of lymphedema, reduce the degree of limb, and increase limb mobility by applying compression therapy.

10.
Acta Pharmacol Sin ; 2021 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-34480113

RESUMO

Spinal cord injury (SCI) is one kind of severe trauma for central nervous system. Myelin debris clearance and axon regeneration are essential for nerve regeneration after SCI. Metformin, a glucose-lowering drug, has been demonstrated to promote the locomotor functional recovery after SCI. In this study, we investigated the role and molecular mechanism of metformin on myelin preservation in a rat SCI model. SCI was induced in rats by compression at T9 level using a vascular clip. We showed that administration of metformin (50 mg·kg-1·d-1, ip) for 28 days significantly improved locomotor function in SCI rats. Metformin also ameliorated SCI-induced neuronal apoptosis and promoted axon regeneration in the spinal cord. Using co-immunofluorescence of IBa-1 and MBP, and luxol fasting blue (LFB) staining, we demonstrated that metformin promoted the transformation of M1 to M2 phenotype polarization of microglial cells, then greatly facilitated myelin debris clearance and protected the myelin in SCI rats. Furthermore, metformin ameliorated SCI-induced blockade of autophagic flux in the spinal cord, and enhanced the fusion of autophagosome and lysosome by inhibiting the AMPK-mTOR signaling pathway. Moreover, metformin significantly attenuated inflammatory responses in the spinal cord. In LPS-treated BV2 cells, pretreatment with metformin (2 mM) significantly enhanced autophagy level, suppressed inflammation and cell apoptosis. The protective effects were blocked in the presence of an autophagy inhibitor 3-methyladenine (3-MA, 5 mM), suggesting that the effect of metformin on autophagy in microglial cells is essential for the myelin preservation during nerve recovery. This study reveals a novel therapeutic effect of metformin in SCI recovery by regulating the activation of microglial cells and enhancing its autophagy level.

11.
Chem Commun (Camb) ; 57(74): 9418-9421, 2021 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-34528965

RESUMO

Fully π-conjugated sp2 carbon covalent organic frameworks upon integration with carboxylic electrolyte sites on the pore wall become highly luminescent sensors. The sensors feature dual channel responsiveness and are able to detect both acids and bases over a wide pH range and the neurotransmitter dopamine via ultrafast electron transfer under ambient conditions.

12.
Front Immunol ; 12: 695491, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34489943

RESUMO

Patients with liver disease are susceptible to infection with Vibrio vulnificus (V. vulnificus), but the specific reasons remain elusive. Through RNA-seq, we found that when mice with alcoholic liver disease (ALD) were infected with V. vulnificus by gavage, compared with the Pair group, the small intestinal genes affecting intestinal permeability were upregulated; and the number of differentially expressed genes related to immune functions (e.g., such as cell chemotaxis, leukocyte differentiation, and neutrophil degranulation) decreased in the liver, spleen, and blood. Further analysis showed that the number of white blood cells decreased in the Pair group, whereas those in the ALD mice did not change significantly. Interestingly, the blood bacterial load in the ALD mice was about 100 times higher than that of the Pair group. After the ALD mice were infected with V. vulnificus, the concentrations of T cell proliferation-promoting cytokines (IL-2, IL-23) decreased. Therefore, unlike the Pair group, ALD mice had weaker immune responses, lower T cell proliferation-promoting cytokines, and higher bacterial loads post-infection, possibly increasing their susceptibility to V. vulnificus infection. These new findings we presented here may help to advance the current understanding of the reasons why patients with liver disease are susceptible to V. vulnificus infection and provides potential targets for further investigation in the context of treatment options for V. vulnificus sepsis in liver disease patient.

13.
J Org Chem ; 2021 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-34494850

RESUMO

A tandem Michael addition-cyclization of nitroalkenes with 1,3-dicarbonyl compounds was developed using phase transfer catalyst (PTC), allowing for the synthesis of polysubstituted-[4,5]-dihydrofuran in high yields. A wide range of substrates were demonstrated by this one-step process. Meanwhile, nitro group was substituted to form corresponding nitrite ion detected in the aqueous phase providing a reasonable pathway for denitrating poisonous and explosive nitro-containing compounds. The proposed mechanism was also supported by our DFT calculations.

14.
Anal Chim Acta ; 1180: 338897, 2021 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-34538312

RESUMO

An europium functionalized metal-organic fluorescent probe, Eu3+@UiO-66-FDC was constructed by post-synthetic modification through coordination interactions. Eu3+@UiO-66-FDC displayed high selectivity and sensitivity toward Tryptophan (Trp) among all the 20 natural amino acids and other general compounds in food and biological samples, with a wide linear concentration range (0-1000 µM), low detection limit (0.29 µM), and a rapid response (<1 min). Besides, this probe was utilized to detect Trp in rabbit blood serum and milk samples with good recoveries, which were verified by high-performance liquid chromatography (HPLC). Notably, this fluorescent probe proved to be a recyclable material. Hence, this work provides a reliable and recyclable fluorescent probe applicable toward the detection of Trp in biological fluids and/or food products.


Assuntos
Európio , Corantes Fluorescentes , Animais , Metais , Coelhos , Triptofano
15.
Int J Med Robot ; : e2333, 2021 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-34533876

RESUMO

BACKGROUND: Recently, thymectomy using minimally invasive approaches has been increasing with the development of robotic video-assisted thoracoscopic surgery (R-VATS). Although multimodal approach is effective for robot assisted thymectomy, it is necessary to determine the approach (left, right or subxiphoid) associated with the least complications. METHODS: An electronic retrieval from PubMed, Embase, Web of Science, GreyNet International and The Cochrane Library. The single-arm meta-analysis was performed to compare the rate of complications of right- and left-side approaches by R-VATS. RESULTS: A total of 21 studies including 930 patients were identified. The pooled incidence of total complications was 12.2% (confidence interval: 10.0%-14.8%) for all studies. The overall complication rate was 17.3% for the right-side compared with 7.4% for the left side (P < 0.001, odds ratio = 2.484, 1.601-3.852). The pooled incidence of air leak was significantly higher for the right versus left side (5.1% vs. 1.2%, respectively; p = 0.004). The incidence of atrial fibrillation was higher for the right-side compared with the left-side approach (4% vs. 1.2%, respectively; p = 0.004). The open conversion rate was significantly higher for the right versus the left-side (6.5% vs. 2.9%, respectively; p = 0.004). However, there was no significant difference in the pooled incidence of pleural effusion and thoracic duct fistula when comparing the right- and left-side approaches. In subgroup analysis, in the left approach, the incidence of overall complications (28.6% vs. 5.5%, respectively; p = 0.002) and pleural effusion (14.3% vs. 1%, respectively; p = 0.002) was higher for the 'Old Age' group compared with the 'Youth' group; However, In the subgroup analysis of gender, there was no significant difference in the incidence of complications after thymectomy. CONCLUSION: Robotic video-assisted thoracoscopic surgery can be performed on the left- and right-sides; however, complications are minimal with the left-side approach. These data demonstrate that the incidence of overall complications, atrial fibrillation, open conversion ratios, and air leak rate of left-side R-VATS thymectomy are lower than those of right-side. Further subgroup analysis showed that the incidence of postoperative complications was higher in the older group.

16.
Lipids Health Dis ; 20(1): 109, 2021 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-34544437

RESUMO

BACKGROUND: Cancer patients often exhibit chemotherapy-associated changes in serum lipid profiles, however, their prognostic value before and after adjuvant chemotherapy on survival among non-small-cell lung cancer (NSCLC) patients is unknown. METHODS: NSCLC patients undergoing radical resection and subsequent adjuvant chemotherapy from 2013 to 2017 at Sun Yat-sen University Cancer Center were retrospectively reviewed. Fasted serum lipid levels were measured before and after chemotherapy. The optimal lipid cut-off values at baseline and fluctuation were determined using X-tile™. The fluctuations in serum lipid levels and disease-free survival (DFS) were assessed. RESULTS: Serum cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C), triglyceride, apolipoprotein (Apo) A-I, and ApoB all significantly increased after adjuvant chemotherapy. X-tile determined 1.52 mmol/L of HDL-C and 0.74 g/L of ApoB as the optimal cut-off values before chemotherapy. Patients with HDL-C ≥ 1.52 mmol/L (median DFS: not reached vs. 26.30 months, P = 0.0005) and a decreased HDL-C level after adjuvant chemotherapy (median DFS: 80.43 vs. 26.12 months, P = 0.0204) had a longer DFS. An HDL-C level that increased by ≥ 0.32 mmol/L after chemotherapy indicated a worse DFS. A high baseline ApoB level were associated with a superior DFS. In the univariate analysis and the multivariate Cox analyses, a high baseline HDL-C level and a HDL-C reduction after adjuvant chemotherapy were independent indicators for superior DFS. High baseline HDL-C was related to N0-1 stage (χ2 = 6.413, P = 0.011), and HDL-C fluctuation was significantly correlated with specific chemotherapy regimens (χ2 = 5.002, P = 0.025). CONCLUSIONS: Adjuvant chemotherapy increased various lipid levels in resected NSCLC patients. A higher HDL-C level before chemotherapy and a reduced HDL-C level after adjuvant chemotherapy were independent predictors of longer DFS in patients with curable NSCLC.

17.
Clin Lab ; 67(9)2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34542977

RESUMO

BACKGROUND: With the development of science and technology, self-service facilities have been widely used in hospitals. This study aimed to assess the microbial contamination characteristics on touch surfaces in outpatient, self-service facilities from Monday to Friday. METHODS: Touch surfaces in outpatient facilities were swabbed and surveyed for total microbial growth before and after work every morning. Selected bacteria were identified to screen for pathogenic organisms. RESULTS: There were 360 samples collected, 87 samples (24.2%) were culture-positive. Staphylococcus species were the main microbial contamination. The three most common bacteria were S. hominis, S. epidermidis and S. hemolyticus. After work, more microbial contamination was found on Monday (p = 0.029). There was no difference in sample positive rates between self-service facilities and manual service area. Although, the antibiotic resistance patterns of different staphylococcus species were different, the overall drug resistance rate is low. Only one S. aureus was methicillin-Sensitive S. aureus. CONCLUSIONS: The self-service facilities' touch surfaces microbial contamination were similar to manual service area, but the more used, the more microbial contamination was found. Hospitals should enhance cleaning times of self-service facilities to keep them clean, especially on Mondays.


Assuntos
Staphylococcus aureus , Tato , Humanos , Meticilina , Pacientes Ambulatoriais , Staphylococcus
18.
Chem Commun (Camb) ; 57(78): 10051-10054, 2021 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-34505863

RESUMO

We herein realize the first example of using a microporous HOF material (ZJU-HOF-1) with suitable pore cavities for highly efficient CO2/CO separation under dry and humid conditions.

19.
Life Sci ; 285: 119959, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34536496

RESUMO

AIMS: Early life stress (ELS) increases the risk of psychiatric diseases such as anxiety disorders and depression in later life. Hyperactivation of the basolateral amygdala (BLA) neurons plays a pivotal role in the pathogenesis of stress-related diseases. However, the functional roles of BLA neurons in ELS-induced anxiety disorders are not completely understood. MAIN METHODS: Mice were subjected to maternal separation (MS) during postnatal days 3 to 21 to mimic ELS. Anxiety-like behavior was tested by open field test (OFT), elevated plus maze (EPM), and novelty suppressed feeding (NSF). Then, c-fos expression, a proxy for neuronal activity, was evaluated by immunofluorescence. Finally, synaptic transmission and intrinsic excitability were measured by whole-cell patch-clamp recordings. KEY FINDINGS: MS significantly increased anxiety-like behavior in adulthood, as indicated by less time spent in the center area of the OFT, less time spent in and fewer entries to the open arms of the EPM, and increased latency to feed in NSF. Mechanistically, MS increased the expression of c-fos in BLA. MS enhanced the excitatory, but not inhibitory, synaptic transmission onto BLA projection neurons (PNs), which was caused by enhanced presynaptic glutamate release. Moreover, MS also markedly increased the intrinsic neuronal excitability of BLA PNs, probably due to the reduced medium afterhyperpolarization (mAHP) in BLA PNs. SIGNIFICANCE: Our results suggest that the changes of neuronal activity and synaptic transmission in the BLA PNs may play a crucial role in ELS-induced anxiety-like behavior, and these findings provide new insights into the pathological mechanisms of stress-related anxiety disorders.

20.
Acta Pharmacol Sin ; 2021 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-34561552

RESUMO

Sepsis is a dysregulated immune response to infection and potentially leads to life-threatening organ dysfunction, which is often seen in serious Covid-19 patients. Disulfiram (DSF), an old drug that has been used to treat alcohol addiction for decades, has recently been identified as a potent inhibitor of the gasdermin D (GSDMD)-induced pore formation that causes pyroptosis and inflammatory cytokine release. Therefore, DSF represents a promising therapeutic for the treatment of inflammatory disorders. Lactoferrin (LF) is a multifunctional glycoprotein with potent antibacterial and anti-inflammatory activities that acts by neutralizing circulating endotoxins and activating cellular responses. In addition, LF has been well exploited as a drug nanocarrier and targeting ligands. In this study, we developed a DSF-LF nanoparticulate system (DSF-LF NP) for combining the immunosuppressive activities of both DSF and LF. DSF-LF NPs could effectively block pyroptosis and inflammatory cytokine release from macrophages. Treatment with DSF-LF NPs showed remarkable therapeutic effects on lipopolysaccharide (LPS)-induced sepsis. In addition, this therapeutic strategy was also applied to treat ulcerative colitis (UC), and substantial treatment efficacy was achieved in a murine colitis model. The underlying mode of action of these DSF-LF-NPs may contribute to efficiently suppressing macrophage-mediated inflammatory responses and ameliorating the complications caused by sepsis and UC. As macrophage pyroptosis plays a pivotal role in inflammation, this safe and effective biomimetic nanomedicine may offer a versatile therapeutic strategy for treating various inflammatory diseases by repurposing DSF.

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