ABSTRACT
Background: The efficacy of Chinese herbal medicine (CHM) in managing irritable bowel syndrome with diarrhea (IBS-D) accompanied by anxiety and depression remains uncertain. Thus, a systematic review was carried out employing meta-analysis and network pharmacology to ascertain the efficacy and underlying mechanisms of CHM therapy. Methods: By conducting a systematic review, including literature search, screening, and data extraction, we identified 25 randomized controlled trials to assess CHM's effectiveness in treating irritable bowel syndrome alongside anxiety and depression. Network pharmacology was utilized to scrutinize the metabolite utility of CHM in addressing this condition. Potential primary mechanisms were synthesized using information sourced from the PubMed database. Results: Twenty-five studies, including 2055 patients, were analyzed, revealing significant treatment efficacy for IBS-D in the trial group compared to controls [OR = 4.01, 95% CI (2.99, 5.36), I2 = 0%] Additionally, treatment for depression [SMD = -1.08, 95% CI (-1.30, -0.86), p < 0.00001, I2 = 68%; SDS: SMD = -1.69, 95% CI (-2.48, -0.90), p < 0.0001, I2 = 96%] and anxiety [HAMA: SMD = -1.29, 95% CI (-1.68, -0.91), p < 0.00001, I2 = 89%; SAS: SMD = -1.75, 95% CI (-2.55, -0.95), p < 0.00001, I2 = 96%] significantly improved in the trial group. Furthermore, the trial group exhibited a significantly lower disease relapse rate [OR = 0.30, 95% CI (0.20, 0.44), p < 0.00001, I2 = 0%]. CHM treatment consistently improved IBS severity (IBS-SSS) and symptom scores. Network pharmacology analysis identified key chemical metabolites in traditional Chinese medicine formulations, including Beta-sitosterol, Stigmasterol, Quercetin, Naringenin, Luteolin, Kaempferol, Nobiletin, Wogonin, Formononetin, and Isorhamnetin. Utilizing the STRING database and Cytoscape v3.9.0 software, a protein-protein interaction (PPI) network revealed the top eight key targets: IL-6, TNF, PPARG, PTGS2, ESR1, NOS3, MAPK8, and AKT1, implicated in anti-inflammatory responses, antioxidant stress modulation, and neurotransmitter homeostasis maintenance. Conclusion: Chinese Herbal Medicine (CHM) offers a promising and safe treatment approach for patients dealing with Diarrheal Irritable Bowel Syndrome (IBS-D) accompanied by anxiety and depression; thus, indicating its potential for practical implementation. The most active metabolites of CHM could simultaneously act on the pathological targets of IBS-D, anxiety, and depression.The diverse scope of CHM's therapeutic role includes various aspects and objectives, underscoring its potential for broad utilization.
ABSTRACT
This study investigates the effects of forest aging on ectomycorrhizal (EcM) fungal community and foraging behavior and their interactions with plant-soil attributes. We explored EcM fungal communities and hyphal exploration types via rDNA sequencing and investigated their associations with plant-soil traits by comparing younger (~120 years) and older (~250 years) temperate forest stands in Northeast China. The results revealed increases in the EcM fungal richness and abundance with forest aging, paralleled by plant-soil feedback shifting from explorative to conservative nutrient use strategies. In the younger stands, Tomentella species were prevalent and showed positive correlations with nutrient availability in both the soil and leaves, alongside rapid increases in woody productivity. However, the older stands were marked by the dominance of the genera Inocybe, Hymenogaster, and Otidea which were significantly and positively correlated with soil nutrient contents and plant structural attributes such as the community-weighted mean height and standing biomass. Notably, the ratios of longer-to-shorter distance EcM fungal exploration types tended to decrease along with forest aging. Our findings underscore the integral role of EcM fungi in the aging processes of temperate forests, highlighting the EcM symbiont-mediated mechanisms adapting to nutrient scarcity and promoting sustainability in plant-soil consortia.
ABSTRACT
Parallel cascade selection molecular dynamics (PaCS-MD) is an enhanced conformational sampling method conducted as a "repetition of time leaps in parallel worlds", comprising cycles of multiple molecular dynamics (MD) simulations performed in parallel and selection of the initial structures of MDs for the next cycle. We developed PaCS-Toolkit, an optimized software utility enabling the use of different MD software and trajectory analysis tools to facilitate the execution of the PaCS-MD simulation and analyze the obtained trajectories, including the preparation for the subsequent construction of the Markov state model. PaCS-Toolkit is coded with Python, is compatible with various computing environments, and allows for easy customization by editing the configuration file and specifying the MD software and analysis tools to be used. We present the software design of PaCS-Toolkit and demonstrate applications of PaCS-MD variations: original targeted PaCS-MD to peptide folding; rmsdPaCS-MD to protein domain motion; and dissociation PaCS-MD to ligand dissociation from adenosine A2A receptor.
Subject(s)
Carrier Proteins , Molecular Dynamics Simulation , Protein Conformation , Software , Protein DomainsABSTRACT
BACKGROUND: The mitochondria-associated endoplasmic reticulum membrane (MAM) is the central hub for endoplasmic reticulum and mitochondria functional communication. It plays a crucial role in hepatic lipid homeostasis. However, even though MAM has been acknowledged to be rich in enzymes that contribute to lipid biosynthesis, no study has yet investigated the exact role of MAM on hepatic neutral lipid synthesis. OBJECTIVES: To address these gaps, this study investigated the systemic control mechanisms of MAM on neutral lipids synthesis by recruiting seipin, focusing on the role of the inositol trisphosphate receptor-1,4,5(Ip3r)-75 kDa glucose-regulated protein (Grp75)-voltage-dependent anion channel (Vdac) complex and their relevant Ca2+ signaling in this process. METHODS: To this end, a model animal for lipid metabolism, yellow catfish (Pelteobagrus fulvidraco), were fed 6 different diets containing a range of palmitic acid (PA) concentrations from 0-150 g/kg in vivo for 10 wk. In vitro, experiments were also conducted to intercept the MAM-mediated Ca2+ signaling in isolated hepatocytes by transfecting them with si-mitochondrial calcium uniporter (mcu). Because mcu was placed in the inner mitochondrial membrane (IMM), si-mcu cannot disrupt MAM's structural integrity. RESULTS: 1. Hepatocellular MAM subproteome analysis indicated excessive dietary PA intake enhanced hepatic MAM structure joined by activating Ip3r-Grp75-Vdac complexes. 2. Dietary PA intake induced hepatic neutral lipid accumulation through MAM recruiting Seipin, which activated lipid droplet biogenesis. Our findings also revealed a previously unidentified mechanism whereby MAM-recruited seipin and controlled hepatic lipid homeostasis, depending on Ip3r-Grp75-Vdac-controlled Ca2+ signaling and not only MAM's structural integrity. CONCLUSIONS: These results offer a novel insight into the MAM-recruited seipin in controlling hepatic lipid synthesis in a MAM structural integrity-dependent and Ca2+ signaling-dependent manner, highlighting the critical contribution of MAM in maintaining hepatic neutral lipid homeostasis.
ABSTRACT
BACKGROUND: The altered respiratory patterns have a significant impact on our health. However, the links between respiration patterns during spontaneous breathing and physical fitness remain unknown. Therefore, we sought to examine how the respiratory pattern during spontaneous breathing interacts with physical fitness. METHODS: A total of 610 participants (aged 20-59 years) were enrolled; 163 men (age = 41 ± 11) and 401 women (age = 42 ± 9) were included for analysis. The parameters of the respiration pattern were respiration rate (RR) and inhalation/exhalation (I/E) ratio. The physical fitness components were body size, visuomotor reaction time, balance, flexibility, hand grip strength, back extension strength, vertical jump height, number of push-ups, number of sit-ups, and the maximum rate of oxygen consumption. The data were analyzed separately for two gender groups. Participants within each gender group were further divided into two age categories (young: 20-39 years, middle-aged: 40-59 years) for the analysis, and both correlational and comparative tests were used to solidify the results. RESULTS: Neither RRs nor the I/E ratios were substantially correlated with physical fitness in women. In addition, the I/E ratios showed no significant correlation with physical fitness in young men, while the results from correlational and comparative tests were inconsistent in middle-aged men. Consistently, men with lower RRs exhibited significantly shorter visuomotor reaction times in two age groups, and demonstrated significantly higher vertical jump heights in the middle-aged group. CONCLUSIONS: In women, respiratory patterns were not correlated with physical fitness. The relationship between middle-aged men's I/E ratios and their physical fitness warrants further investigation. Men with lower RRs may have better visual-motor coordination and/or sustained attention, while middle-aged men with lower RRs may also have greater leg explosive power and neuromuscular coordination, which should be considered for physical assessment and health improvement.
Subject(s)
Hand Strength , Physical Fitness , Adult , Male , Middle Aged , Humans , Female , Cross-Sectional Studies , Exercise , Exercise TestABSTRACT
Choline plays a crucial role in hepatic lipid homeostasis by acting as a major methyl-group donor. However, despite this well-accepted fact, no study has yet explored how choline's methyl-donor function contributes to preventing hepatic lipid dysregulation. Moreover, the potential regulatory role of Ire-1α, an ER-transmembrane transducer for the unfolded protein response (UPRer), in choline-mediated hepatic lipid homeostasis remains unexplored. Thus, this study investigated the mechanism by which choline prevents hepatic lipid dysregulation, focusing on its role as a methyl-donor and the involvement of Ire-1α in this process. To this end, a model animal for lipid metabolism, yellow catfish (Pelteobagrus fulvidraco) were fed two different diets (adequate or deficient choline diets) in vivo for 10 weeks. The key findings of studies are as follows: 1. Dietary choline, upregulated selected lipolytic and fatty acid ß-oxidation transcripts promoting hepatic lipid homeostasis. 2. Dietary choline ameliorated UPRer and prevented hepatic lipid dysregulation mainly through ire-1α signalling, not perk or atf-6α signalling. 3. Choline inhibited the transcriptional expression level of ire-1α by activating site-specific DNA methylations in the promoter of ire-1α. 4. Choline-mediated ire-1α methylations reduced Ire-1α/Fas interactions, thereby further inhibiting Fas activity and reducing lipid droplet deposition. These results offer a novel insight into the direct and indirect regulation of choline on lipid metabolism genes and suggests a potential crosstalk between ire-1α signalling and choline-deficiency-induced hepatic lipid dysregulation, highlighting the critical contribution of choline as a methyl-donor in maintaining hepatic lipid homeostasis.
Subject(s)
Catfishes , Lipotropic Agents , Animals , Lipotropic Agents/metabolism , Choline/pharmacology , Choline/metabolism , Catfishes/metabolism , Liver/metabolism , Lipid Metabolism , Homeostasis , LipidsABSTRACT
Existing methods for Salient Object Detection in Optical Remote Sensing Images (ORSI-SOD) mainly adopt Convolutional Neural Networks (CNNs) as the backbone, such as VGG and ResNet. Since CNNs can only extract features within certain receptive fields, most ORSI-SOD methods generally follow the local-to-contextual paradigm. In this paper, we propose a novel Global Extraction Local Exploration Network (GeleNet) for ORSI-SOD following the global-to-local paradigm. Specifically, GeleNet first adopts a transformer backbone to generate four-level feature embeddings with global long-range dependencies. Then, GeleNet employs a Direction-aware Shuffle Weighted Spatial Attention Module (D-SWSAM) and its simplified version (SWSAM) to enhance local interactions, and a Knowledge Transfer Module (KTM) to further enhance cross-level contextual interactions. D-SWSAM comprehensively perceives the orientation information in the lowest-level features through directional convolutions to adapt to various orientations of salient objects in ORSIs, and effectively enhances the details of salient objects with an improved attention mechanism. SWSAM discards the direction-aware part of D-SWSAM to focus on localizing salient objects in the highest-level features. KTM models the contextual correlation knowledge of two middle-level features of different scales based on the self-attention mechanism, and transfers the knowledge to the raw features to generate more discriminative features. Finally, a saliency predictor is used to generate the saliency map based on the outputs of the above three modules. Extensive experiments on three public datasets demonstrate that the proposed GeleNet outperforms relevant state-of-the-art methods. The code and results of our method are available at https://github.com/MathLee/GeleNet.
ABSTRACT
OBJECTIVE: To detect the relative expression of IGLL1 (immunoglobulin lambda-like polypeptide 1) mRNA in bone marrow of children with T-cell acute lymphoblastic leukemia (T-ALL), and analyze its correlation with the clinical characteristics and prognosis of the patients, so as to clarify the clinical significance of IGLL1 in pediatric T-ALL patients. METHODS: A total of 56 pediatric T-ALL patients hospitalized in Children's Hospital of Soochow University from June 2012 to December 2017 and treated with CCLG-ALL 2008 regimen were selected. Transcriptome sequencing technology was used to detect the transcription level of IGLL1 gene in children with T-ALL. According to 25% of the IGLL1 transcription level (cutoff value:448), the enrolled children were divided into IGLL1 low expression group (17 cases) and IGLL1 high expression group (39 cases). Combined with clinical data, the correlation between the expression level of IGLL1 and prognosis of the patients was analyzed. RESULTS: The comparative analysis showed that the transcription level of IGLL1 was not correlated with the clinical characteristics of the patients, such as sex, age, bone marrow blast, white blood cell (WBC) count at initial diagnosis. The 5-year OS rate of patients with high IGLL1 expression was significantly higher than that of patients with low IGLL1 expression (76.9%±6.7% vs 47.1%±12.1%, P =0.018). Further comparison of relapse-free survival (RFS) rate between the two groups showed that the 5-year RFS rate of patients with high IGLL1 expression was higher than that of patients with low IGLL1 expression, but the difference between the two groups was not statistically significant (P =0.095). Multivariate COX analysis was conducted on common clinical prognostic factors (age, sex, WBC count at diagnosis, prednisone response on the 7th day, bone marrow response on the 15th day after treatment) and IGLL1 expression level, and the results showed that IGLL1 expression (P =0.012) and prednisone response (P =0.017) were independent risk factors for overall survival in pediatric T-ALL patients. CONCLUSION: In pediatric T-ALL, the OS rate of children with high expression of IGLL1 gene was significantly higher than that of children with low expression of IGLL1 gene, and the expression level of IGLL1 gene was an independent factor affecting the survival of children with T-ALL, which suggests that IGLL1 is a marker of good clinical prognosis of children with T-ALL.
Subject(s)
Immunoglobulin Light Chains, Surrogate , Precursor T-Cell Lymphoblastic Leukemia-Lymphoma , Child , Humans , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Clinical Relevance , Disease-Free Survival , Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/genetics , Prednisone/therapeutic use , Prognosis , Recurrence , Immunoglobulin Light Chains, Surrogate/geneticsABSTRACT
Introduction: Intensive and long-lasting office work is a common cause of muscular and mental disorders due to workplace stressors. Mindful and slow breathing exercises decrease psychological stress and improve mental health, whereas fast breathing increases neuronal excitability. This study aimed to explore the influence of 5 min of mindful breathing (MINDFUL), slow breathing (SLOW), fast breathing (FAST), and listening to music (MUSIC) on muscle tension and executive function during an intensive psychological task. Methods: Forty-eight participants (24 men and 24 women) were enrolled. Muscle tension was recorded using surface electromyography, and executive function was assessed using the Stroop Color and Word Test (Stroop Test). The respiration rate (RR), oxygen saturation (SpO2), end-tidal carbon dioxide (EtCO2), and the subjects' preferred method were also recorded. During the experiment, participants performed a one-time baseline test (watching a neutral video for 5 min) and then completed 5 min of MUSIC, MINDFUL, SLOW, and FAST in a random sequence. The Stroop Test was performed after each intervention, including the baseline test, and was followed by a 5 min rest before performing the next intervention. Results: None of the methods significantly influenced muscular activity and performance of the Stroop Test in both men and women, based on the average 5 min values. However, at the fifth minute, men's accuracy rate in the Stroop Test was significantly higher after SLOW than after MUSIC and FAST, and the reaction time after the SLOW was the shortest. SpO2 was significantly higher during SLOW than during MUSIC, and RR was relatively lower after SLOW than after MUSIC. Most men preferred SLOW, and most women preferred MUSIC, whereas FAST was the most unfavorable method for both men and women. Conclusion: Brief breathing exercises did not substantially affect muscle tension under psychological stress. SLOW demonstrated greater potential for sustaining executive function in men, possibly via its superior respiration efficiency on SpO2 and inhibition of RR.
ABSTRACT
Background and Objectives: The current study aimed to better understand the changes in respiration that occur with aging in men and women to provide accurate recommendations for breathing exercises to improve health. Materials and Methods: A total of 610 healthy subjects, aged 20 to 59, participated in the study. They performed quiet breathing while wearing two respiration belts (Vernier, Beaverton, OR, USA) at the height of the navel and at the xiphoid process to record abdominal motion (AM) and thoracic motion (TM), respectively. Vital capacity, representing maximal inhalation movement, was measured using a spirometer (Xindonghuateng, Beijing, China). After exclusion, 565 subjects (164 men, aged 41 ± 11; 401 women, aged 42 ± 9) were included for statistical analysis using the Kruskal-Wallis U test and stepwise multiple linear regression. Results: Abdominal motion and its contribution to spontaneous breathing were significantly larger for older men, while the contribution of thoracic motion was smaller for older men. There was no significant difference in thoracic motion between the younger and older men. The differences in women's respiratory movements among various ages were mild and negligible. The contribution of thoracic motion to spontaneous breathing in women was larger than in men for those of older ages (40-59 years), but not for those of younger ages (20-39 years). Additionally, men's and women's vital capacities were less in those of older ages, and the men's were larger than the women's. Conclusions: The findings indicate that men's abdominal contribution to spontaneous breathing increased from 20 to 59 years of age due to increased abdominal motion. Women's respiratory movements did not change much with aging. The maximal inhalation movement became smaller with aging for men and women. Healthcare professionals should focus on improving thoracic mobility when addressing health concerns about aging.
Subject(s)
Movement , Respiration , Male , Humans , Female , Aged , Young Adult , Adult , Middle Aged , Abdomen , Multivariate Analysis , ChinaABSTRACT
Acute lung injury (ALI) caused by sepsis is a common respiratory critical illness with high morbidity and mortality. Protein kinase C-alpha (PRKCA) plays a protective role in sepsis-induced ALI. However, the detailed molecular mechanism of PRKCA in ALI caused by sepsis is unclear. Animal and cell models of sepsis were established by cecal ligation and puncture (CLP)-surgery and lipopolysaccharide (LPS)/interferon-gamma (IFN-γ) treatment, respectively. Lentivirus transfection was used to overexpress PRKCA. H&E staining and lung injury in CLP-surgery mice were evaluated. Gene expression was evaluated using qPCR and Western blotting. The expression of TNF-α, IL-1ß, and IL-6 was examined using qPCR and ELISA. The expression of LC3 and TOM20 was evaluated using immunofluorescence assays. Cell apoptosis was assessed using a flow cytometry assay. The bond between miR-15a-5p and PDK4 was confirmed by dual-luciferase reporter gene and RNA immunoprecipitation assays. In vivo and in vitro, PRKCA overexpression reduced lung injury to prompt mitophagy and inhibit the inflammatory response, ROS production, and cell apoptosis. miR-15a-5p was highly expressed in macrophages treated with LPS/IFN-γ and was negatively mediated by PRKCA. The overexpression of miR-15a-5p reduced the effects of PRKCA upregulation in macrophages. miR-15a-5p could restrain mitophagy in LPS/IFN-γ-treated macrophages by directly targeting PDK4. Furthermore, PDK4 knockdown reversed the inhibition of cell apoptosis and inflammatory factor release caused by miR-15a-5p silencing. The PRKCA/miR-15a-5p/PDK4 axis alleviated ALI caused by sepsis by promoting mitophagy and repressing anti-inflammatory response.
Subject(s)
Acute Lung Injury , MicroRNAs , RNA, Long Noncoding , Sepsis , Animals , Mice , Acute Lung Injury/etiology , Apoptosis/genetics , Lipopolysaccharides , MicroRNAs/genetics , MicroRNAs/metabolism , Mitophagy , Protein Kinase C-alpha , Sepsis/complications , Sepsis/geneticsABSTRACT
High-fat diets (HFD) lead to impairment of chylomicrons (CMs) assembly and adversely influence intestinal lipid homeostasis. However, the mechanisms of HFD impairing CMs assembly have yet to be fully understood. Additionally, although choline, as a lipid-lowering agent, has been widely used and its deficiency has been closely linked to non-alcoholic steatohepatitis (NASH), the contribution of choline by functioning as a methyl donor in alleviating HFD-induced intestinal lipid deposition is unknown. Thus, this study was conducted to determine the mechanism of HFD impairing CMs assembly and also tested the effect of choline acting as a methyl donor in this process. To this end, in this study, four diets (control, HFD, choline and HFD + choline diet) were fed to yellow catfish for 10 weeks in vivo and their intestinal epithelial cells were isolated and incubated for 36 h in fatty acids (FA) with or without choline solution combining si-perk transfection in vitro. The key findings from this study as follows: (1) HFD caused impairment of CMs assembly main by unfolded protein response (UPRer). HFD activated perk and then induced UPRer, which led to endoplasmic reticulum dysfunction and further impaired CMs assembly via protein-protein interactions between Perk and Apob48. (2) Choline inhibited the transcriptional expression level of perk via activating the -211 CpG methylation site, which initiated the subsequent ameliorating effect on HFD-impaired CMs assembly and intestinal lipid dysfunction. These results provide a new insight into direct crosstalk between UPRer and CMs assembly, and also emphasize the critical contribution of choline acting as a methyl donor and shed new light on choline-deficient diet-induced NASH.
Subject(s)
Diet, High-Fat , Non-alcoholic Fatty Liver Disease , Humans , Choline/pharmacology , DNA Methylation , Non-alcoholic Fatty Liver Disease/etiology , Unfolded Protein Response , LipidsABSTRACT
BACKGROUND: Abdominal/diaphragmatic breathing exercises are popular worldwide and have been proven to be beneficial for physical performance. Is abdominal motion (AM) during spontaneous breathing correlated with physical fitness? The present study aimed to answer this question. METHODS: 434 women (aged 20-59) were enrolled and participated in respiration tests using two respiration belts (one was tied at the height of the xiphoid and another at the navel) to detect AM and thoracic motion (TM). They also performed physical fitness tests to measure body size, muscular strength, muscular power, muscular endurance, balance, flexibility, reaction time, and cardiorespiratory endurance. RESULTS: All the correlation coefficients between respiratory movements (AM, TM, AM + TM, AM/(AM + TM)) and physical fitness outcomes were less than 0.4/-0.4. Only AM and muscular power (countermovement jump height) had a weak correlation, with a correlation coefficient close to 0.4 in the 20-29-year age group (rs = 0.398, p = 0.011, n = 40). CONCLUSIONS: Women's respiratory movements during spontaneous breathing were not correlated with physical fitness. Future studies may focus on the relationship between AM and countermovement jump height in young women with a larger sample size and using ultrasound to directly test the excursion of the diaphragm.
Subject(s)
Cardiorespiratory Fitness , Physical Fitness , Adult , Body Height , Cross-Sectional Studies , Female , Humans , Muscle Strength , Physical Endurance , Respiration , Young AdultABSTRACT
Hodgkin lymphoma (HL)-related hemophagocytic lymphohistiocytosis (HLH) has been reported in the literature; however, there is almost no literature on the factors related to HL triggering HLH. One hundred forty patients with HL were retrospectively analyzed. The incidence of HL-related HLH (we call HL-related HLH as HL-HLH). And all HL-HLH patients in our cohort had HLH as the first manifestation and its clinical characteristics and the role of intrathoracic infection (ITI) in triggering HLH are discussed. The 140 patients with HL mainly included mixed-cellularity classic HL (MCCHL) in 81 (57.9%), nodular sclerosis classic HL (NSCHL) in 36 (25.7%), and lymphacyte-rich classic HL in 14 (10.0%) patients. Of the 137 patients who underwent chest computed tomography scans on admission, 44 had ITI, and most of these ITI were mildly ill and had no respiratory symptoms. Among 140 HL patients, 8 patients from MCCHL were diagnosed as HL-HLH. Among 81 MCCHL patients, 26 patients with ITI had a significantly higher incidence of HL-HLH than those without ITI (26.9% vs 1.8%, P = .002). The median survival time of 8 cases of HL-HLH was only 2 months. When HL patients were first admitted to the hospital, 5.7% had HLH as the first manifestation, and 32.1% had ITI. These ITI can cooperate with HL to trigger HLH, despite their mild illness. The prognosis of HL-HLH was poor.
Subject(s)
Hodgkin Disease , Lymphohistiocytosis, Hemophagocytic , Hodgkin Disease/complications , Hodgkin Disease/epidemiology , Hospitalization , Hospitals , Humans , Lymphohistiocytosis, Hemophagocytic/epidemiology , Retrospective StudiesABSTRACT
The mitochondrial unfolded protein response (UPRmt) is known as a conservative mechanism in response to mitochondrial dysfunction. Thus, based on UPRmt, this study was conducted to determine the mechanism of a high-fat diet (HFD) inducing mitochondrial dysfunction and its role in stimulating hepatic lipid dysregulation. The choline-activated alleviating effect was also evaluated. In vivo, yellow catfish were fed three diets (control, HFD, and HFD + choline diet) for 10 weeks. In vitro, hepatocytes isolated from yellow catfish and the HepG2 cell line were cultured and incubated with fatty acid (FA) for 48 h. (1) HFD-induced mitochondrial dysfunction via SIRT3/mtHSP70-mediated UPRmt. HFD inhibited the subcellular localization of SIRT3 into the mitochondrion, resulting in the up-regulating of mtHSP70 acetylation via lysine residues 493 and 507. The mtHSP70 acetylation promoted the stability of mtHSP70, which then led to the UPRmt and further mitochondrial dysfunction. (2) SIRT3/mtHSP70-mediated UPRmt regulated HFD/FA-induced hepatic lipid dysregulation. SIRT3/mtHSP70-mediated UPRmt reduced FA ß-oxidation via mitochondrial dysfunction and then led to lipid dysregulation. Additionally, the mtHSP70-ACOX1 interaction was confirmed. (3) Choline alleviated HFD-induced UPRmt via up-regulating the localization of SIRT3 into the mitochondrion, which in turn led to the subsequent ameliorating effect on HFD-induced hepatic lipid dysregulation. Through SIRT3-mediated mtHSP70 deacetylation, dietary choline alleviates HFD-induced hepatic lipid dysregulation via UPRmt. This provides the first proof of acetylation regulating UPRmt and the crosstalk between UPRmt and FA ß-oxidation.
Subject(s)
Sirtuin 3 , Choline/metabolism , Choline/pharmacology , Diet, High-Fat/adverse effects , Fatty Acids/metabolism , Liver/metabolism , Sirtuin 3/genetics , Sirtuin 3/metabolismABSTRACT
The treatment of tongue squamous cell carcinoma (TSCC) faces challenges because TSCC has an aggressive biological behavior and manifests usually as widespread metastatic disease. Therefore, it is particularly important to screen out and develop drugs that inhibit tumor invasion and metastasis. Two-dimensional (2D) cell culture has been used as in vitro models to study cellular biological behavior, but growing evidence now shows that the 2D systems can result in cell bioactivities that deviate appreciably the in vivo response. It is urgent to develop a novel 3D cell migration model in vitro to simulate the tumor microenvironment as much as possible and screen out effective anti-migration drugs. Sodium alginate, has a widely used cell encapsulation material, as significant advantages. We have designed a microfluidic device to fabricate a hollow alginate hydrogel microtube model. Based on the difference in liquid flow rate, TSCC cells (Cal27) were able to be evenly distributed in the hollow microtubes, which was confirmed though fluorescence microscope and laser scanning confocal microscope (LSCM). Our microfluidic device was cheap, and commercially available and could be assembled in a modular way, which are composed of a coaxial needle, silicone hose, and syringes. It was proved that the cells grow well in artificial microtubes with extracellular matrix (ECM) proteins by LSCM and flow cytometry. Periodic motility conferred a different motor state to the cells in the microtubes, more closely resembling the environment in vivo. The quantitative analysis of tumor cell migration could be achieved simply by determining the position of the cell in the microtube cross-section. We verified the anti-migration effects of three NSAIDs drugs (aspirin, indomethacin, and nimesulide) with artificial microtubes, obtaining the same results as conventional migration experiments. The results showed that among the three NSAIDs, nimesulide showed great anti-migration potential against TSCC cells. Our method holds great potential for application in the more efficient screening of anti-migration tumor drugs.
ABSTRACT
Patients with subcutaneous panniculitis-like T-cell lymphoma (SPTCL) are prone to the development of hemophagocytic lymphohistiocytosis (HLH). It is not known whether small infections in SPTCL patients can trigger the development of HLH. The clinical data were collected from 21 SPTCL patients admitted to our hospital from January 2006 to October 2019. Among 21 cases of SPTCL, six cases had HLH as the first manifestation (SPTCL/HLH), seven cases had intrathoracic infection (ITI), five cases were SPTCL/HLH, 13 cases had no ITI or HLH (SPTCL/no HLH). Two patients with SPTCL/noHLH healed spontaneously. We found that 28.6% of the SPTCL patients had HLH as the first presentation. ITI may cooperate with SPTCL to trigger HLH and a small number of SPTCL/noHLH can fully recover without treatment.
Subject(s)
Lymphohistiocytosis, Hemophagocytic , Lymphoma, T-Cell , Panniculitis , Humans , Lymphohistiocytosis, Hemophagocytic/diagnosis , Lymphohistiocytosis, Hemophagocytic/etiology , Lymphoma, T-Cell/complications , Lymphoma, T-Cell/diagnosis , Panniculitis/diagnosis , Panniculitis/etiologyABSTRACT
Cupping therapy is an important part of traditional Chinese medicine, and its efficacy has been gradually accepted and confirmed by modern clinical medicine, but its physiological mechanisms have no consensus. In the present paper, we summarized the related mechanisms from results of both domestic and international researches which include 1) blood circulation promotion theory, 2) neurological reflex theory, 3) gate theory of pain, 4) inflammation-immune reaction theory and 5) skin tension increase theory. We also reviewed progresses of clinical researches about application of cupping therapy to cardiovascular diseases, chronic musculoskeletal pain, migraine and other painful symptoms, as well as arthritis which effects involve the above mentioned blood-circulation promotion, tension-increase, gate theory and inflammation-immune reaction, respectively. We believe that the mechanisms of cupping therapy are not independent and should be explored further from different perspectives.
Subject(s)
Chronic Pain , Cupping Therapy , Humans , Inflammation , Medicine, Chinese Traditional , SkinABSTRACT
Existing RGB-D Salient Object Detection (SOD) methods take advantage of depth cues to improve the detection accuracy, while pay insufficient attention to the quality of depth information. In practice, a depth map is often with uneven quality and sometimes suffers from distractors, due to various factors in the acquisition procedure. In this article, to mitigate distractors in depth maps and highlight salient objects in RGB images, we propose a Hierarchical Alternate Interactions Network (HAINet) for RGB-D SOD. Specifically, HAINet consists of three key stages: feature encoding, cross-modal alternate interaction, and saliency reasoning. The main innovation in HAINet is the Hierarchical Alternate Interaction Module (HAIM), which plays a key role in the second stage for cross-modal feature interaction. HAIM first uses RGB features to filter distractors in depth features, and then the purified depth features are exploited to enhance RGB features in turn. The alternate RGB-depth-RGB interaction proceeds in a hierarchical manner, which progressively integrates local and global contexts within a single feature scale. In addition, we adopt a hybrid loss function to facilitate the training of HAINet. Extensive experiments on seven datasets demonstrate that our HAINet not only achieves competitive performance as compared with 19 relevant state-of-the-art methods, but also reaches a real-time processing speed of 43 fps on a single NVIDIA Titan X GPU. The code and results of our method are available at https://github.com/MathLee/HAINet.