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2.
Brain Behav Immun ; 117: 412-427, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38320683

RESUMO

Rheumatoid arthritis (RA) patients have a high prevalence for depression. On the other hand, comorbid with depression is associated with worse prognosis for RA. However, little is known about the underlying mechanisms for the comorbidity between RA and depression. It remains to be elucidated which brain region is critically involved in the development of depression in RA, and whether alterations in the brain may affect pathological development of RA symptoms. Here, by combining clinical and animal model studies, we show that in RA patients, the level of depression is significantly correlated with the severity of RA disease activity and affects patients' quality of life. The collagen antibody-induced arthritis (CAIA) mouse model of RA also develops depression-like behaviors, accompanied by hyperactivity and alterations in gene expression reflecting cerebrovascular disruption in the lateral habenula (LHb), a brain region critical for processing negative valence. Importantly, inhibition of the LHb not only alleviates depression-like behaviors, but also results in rapid remission of RA symptoms and amelioration of RA-related pathological changes. Together, our study highlights a critical but previously overlooked contribution of hyperactive LHb to the comorbidity between RA and depression, suggesting that targeting LHb in conjunction with RA treatments may be a promising strategy for RA patients comorbid with depression.


Assuntos
Artrite Experimental , Artrite Reumatoide , Habenula , Animais , Camundongos , Humanos , Depressão/epidemiologia , Qualidade de Vida , Artrite Reumatoide/complicações , Comorbidade
3.
CVIR Endovasc ; 7(1): 16, 2024 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-38294662

RESUMO

PURPOSE: To analyze the selection of endovascular treatment strategies and the efficacy of various locations and types of splenic artery aneurysms (SAAs). METHODS: Sixty-three cases of patients diagnosed with SAA from January 2016 to October 2021 were collected, and their clinical data and follow-up results were analyzed. RESULTS: Among the 63 patients, 55 had true SAAs, and 8 had false SAAs. The average diameter of the true SAAs was 2.0 ± 0.8 cm. There were 10 cases of intra-aneurysm embolization, 24 cases of intra-aneurysm and aneurysm-bearing artery embolization, 10 cases of bare stent-assisted coil embolization, and 11 cases of stent grafts. The false SAAs had an average diameter of 2.3 ± 1.1 cm. Aneurysm-bearing artery embolization was applied in 5 cases, and stent grafts were applied in 3 cases. The incidence of complications after embolization of the aneurysm-bearing artery was higher (P < 0.01). Postembolization syndrome occurred in 10 patients; 7 patients developed splenic infarction to varying degrees, 1 patient had mildly elevated blood amylase, and 1 patient developed splenic necrosis with abscess formation, all of which improved after active treatment. The average length of hospital stay was 5.5 ± 3.2 days. The average follow-up time was 17.2 ± 16.1 months, and the aneurysm cavity of all patients was completely thrombotic. CONCLUSION: Endovascular treatments of SAAs are safe and effective. For various locations and types of SAAs, adequate selection of treatment is necessary. Stent grafts are recommended for their safety, economy, practicality, and preservation of the physiological functions of the human body.

4.
Front Immunol ; 14: 1195553, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37662902

RESUMO

Background: Studies of liver dysfunction in relation to bone and joint-related diseases are scarce, and its causality remains unclear. Our objective was to investigate whether serum liver enzymes are causally associated with bone and joint-related diseases using Mendelian randomization (MR) designs. Methods: Genetic data on serum liver enzymes (alkaline phosphatase (ALP); alanine transaminase (ALT); gamma-glutamyl transferase (GGT)) and six common bone and joint-related diseases (rheumatoid arthritis (RA), osteoporosis, osteoarthritis (OA), ankylosing spondylitis, psoriatic arthritis, and gout) were derived from independent genome-wide association studies of European ancestry. The inverse variance-weighted (IVW) method was applied for the main causal estimate. Complementary sensitivity analyses and reverse causal analyses were utilized to confirm the robustness of the results. Results: Using the IVW method, the positive causality between ALP and the risk of osteoporosis diagnosed by bone mineral density (BMD) at different sites was indicated (femoral neck, lumbar spine, and total body BMD, odds ratio (OR) [95% CI], 0.40 [0.23-0.69], 0.35 [0.19-0.67], and 0.33 [0.22-0.51], respectively). ALP was also linked to a higher risk of RA (OR [95% CI], 6.26 [1.69-23.51]). Evidence of potential harmful effects of higher levels of ALT on the risk of hip and knee OA was acquired (OR [95% CI], 2.48 [1.39-4.41] and 3.07 [1.49-6.30], respectively). No causal relationship was observed between GGT and these bone and joint-related diseases. The study also found that BMD were all negatively linked to ALP levels (OR [95% CI] for TBMD, FN-BMD, and LS-BMD: 0.993 [0.991-0.995], 0.993 [0.988-0.998], and 0.993 [0.989, 0.998], respectively) in the reverse causal analysis. The results were replicated via sensitivity analysis in the validation process. Conclusions: Our study revealed a significant association between liver function and bone and joint-related diseases.


Assuntos
Artrite Reumatoide , Osteoartrite do Joelho , Osteoporose , Humanos , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Alanina Transaminase , gama-Glutamiltransferase , Osteoporose/genética , Fosfatase Alcalina/genética , Corantes , Fígado
5.
Front Cell Dev Biol ; 11: 1161667, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37745305

RESUMO

The expression characteristics of non-coding RNA (ncRNA) in colon adenocarcinoma (COAD) are involved in regulating various biological processes. To achieve these functions, ncRNA and a member of the Argonaute protein family form an RNA-induced silencing complex (RISC). The RISC is directed by ncRNA, especially microRNA (miRNA), to bind the target complementary mRNAs and regulate their expression by interfering with mRNA cleavage, degradation, or translation. However, how to identify potential miRNA biomarkers and therapeutic targets remains unclear. Here, we performed differential gene screening based on The Cancer Genome Atlas dataset and annotated meaningful differential genes to enrich related biological processes and regulatory cancer pathways. According to the overlap between the screened differential mRNAs and differential miRNAs, a prognosis model based on a least absolute shrinkage and selection operator-based Cox proportional hazards regression analysis can be established to obtain better prognosis characteristics. To further explore the therapeutic potential of miRNA as a target of mRNA intervention, we conducted an immunohistochemical analysis and evaluated the expression level in the tissue microarray of 100 colorectal cancer patients. The results demonstrated that the expression level of POU4F1, DNASE1L2, and WDR72 in the signature was significantly upregulated in COAD and correlated with poor prognosis. Establishing a prognostic signature based on miRNA target genes will help elucidate the molecular pathogenesis of COAD and provide novel potential targets for RNA therapy.

6.
Langenbecks Arch Surg ; 408(1): 249, 2023 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-37380790

RESUMO

BACKGROUND: In laparoscopic low anterior resection for rectal cancer surgery, there has been controversy to whether the inferior mesenteric artery (IMA) should be ligated at the origin of its aorta (high ligation (HL)) or below the branches of the left colonic artery (LCA) (low ligation (LL)). This study was intended to clarify oncological outcome and long-term prognosis of retrospective analysis. METHODS: Analyzed the cases who underwent laparoscopic low anterior resection (LAR) in Shanghai Ruijin Hospital from January 2015 to December 2016, 357patients scheduled into 2 groups according to the level of IMA ligation: HL (n = 247) versus LL (n = 110). RESULTS: The primary endpoint is long-term outcomes, and the secondary endpoint is the incidence rate of major postoperative complications. There were no significant differences in 5-year overall survival (P = 0.92) and 5-year disease-free survival (P = 0.41). There were no differences between the clinical baseline levels in each group. The incidence of low anterior resection syndrome (LARS) in the two groups was statistically significant (P = 0.037). No significant differences were observed in operative time (P = 0.092) and intraoperative blood loss (P = 0.118). In the HL group, 6 cases (2.4%) had additional colonic excision due to poor anastomotic blood supply; none of the colonic anastomosis in the low ligation group had ischemic manifestations, and length from the proximal margin (P = 0.076), length from the distal margin (P = 0.184), the total number of lymph nodes excised (P = 0.065), and anastomotic leakage incidence (P = 0.33). CONCLUSION: Low ligation of the IMA which reserved LCA with vascular root lymph node dissection in laparoscopic low anterior resection for rectal cancer surgery may help protect the blood supply of the anastomosis, and will not increase postoperative complications while enhance recovery, without compromising radical excision and long-term prognosis.


Assuntos
Laparoscopia , Neoplasias Retais , Humanos , Estudos Retrospectivos , Complicações Pós-Operatórias/epidemiologia , Artéria Mesentérica Inferior/cirurgia , Neoplasias Retais/cirurgia , China
7.
Phytomedicine ; 116: 154840, 2023 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-37172477

RESUMO

BACKGROUND: Pancreatic intraepithelial neoplasia (PanIN) is the most common precursor lesion of pancreatic ductal adenocarcinoma (PDAC), which is a highly malignant tumor and lack of effective treatment. Although Xiao Chai Hu Tang (XCHT) has a good therapeutic effect on pancreatic cancer patients with advanced stage, the effect and mechanism of XCHT remains unclear in pancreatic tumorigenesis. PURPOSE: To assess the therapeutic effects of XCHT on the malignant transformation from PanIN to PDAC and to reveal its mechanisms of pancreatic tumorigenesis. METHODS: Syrian golden hamster were induced by N-Nitrosobis (2-oxopropyl) amine (BOP) to establish the pancreatic tumorigenesis model. The morphological changes of pancreatic tissue were observed by H&E and Masson staining; the Gene ontology (GO) analysis the transcriptional profiling changes; the mitochondrial ATP generation, mitochondrial redox status, mitochondrial DNA (mtDNA) N6-methyladenine (6mA) level and relative mtDNA genes expressions were examined. In addition, immunofluorescence detect the cell localization of 6mA in human pancreatic cancer PANC1 cell. Using the TCGA database, the prognostic effect of mtDNA 6mA demethylation ALKBH1 expression on pancreatic cancer patients was analyzed. RESULTS: We confirmed the mtDNA 6mA levels were gradually increased with the mitochondrial dysfunction in PanINs progression. XCHT showed the effect to inhibit the occurrence and development of pancreatic cancer in Syrian hamster pancreatic tumorigenesis model. In addition, the lack of ALKBH1 mediated mtDNA 6mA increase, mtDNA coded genes down-expression and abnormal redox status were rescued by XCHT. CONCLUSIONS: ALKBH1/mtDNA 6mA mediated mitochondrial dysfunction to induce the occurrence and progression of pancreatic cancer. XCHT can improve ALKBH1 expression and mtDNA 6mA level, regulate the oxidative stress and expression of mtDNA coded genes. This study investigated a new molecular mechanism of pancreatic tumorigenesis, and revealed the therapeutic efficacy of XCHT in pancreatic tumorigenesis for the first time.


Assuntos
Bupleurum , Neoplasias Pancreáticas , Animais , Cricetinae , Humanos , DNA Mitocondrial/genética , Mesocricetus , Carcinogênese , Transformação Celular Neoplásica , Neoplasias Pancreáticas/induzido quimicamente , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/genética , Mitocôndrias , Homólogo AlkB 1 da Histona H2a Dioxigenase , Neoplasias Pancreáticas
8.
Front Plant Sci ; 14: 1188981, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37255557

RESUMO

Currently, mechanical and chemical damage is the main way to carry out weed control. The use of chlorophyll fluorescence (CF) technology to nondestructively monitor the stress physiological state of weeds is significant to reveal the damage mechanism of mechanical and chemical stresses as well as complex stresses. Under simulated real field environmental conditions, different species and leaf age weeds (Digitaria sanguinalis 2-5 leaf age, and Erigeron canadensis 5-10 leaf age) were subjected to experimental treatments for 1-7 days, and fluorescence parameters were measured every 24 h using a chlorophyll fluorometer. The aim of this study was to investigate the changes in CF parameters of different species of weeds (Digitaria sanguinalis, Erigeron canadensis) at their different stress sites under chemical, mechanical and their combined stresses. The results showed that when weeds (Digitaria sanguinalis and Erigeron canadensis) were chemically stressed in different parts, their leaf back parts were the most severely stressed after 7 days, with photosynthetic inhibition reaching R=75%. In contrast, mechanical stress differs from its changes, and after a period of its stress, each parameter recovers somewhat after 1 to 2 days of stress, with heavy mechanical stress R=11%. Complex stress had the most significant effect on CF parameters, mainly in the timing and efficiency of changes in Fv/Fm, Fq'/Fm', ETR, Rfd, NPQ and Y(NO), with R reaching 71%-73% after only 3-4 days of complex stress, and its changes in complex stress were basically consistent with the pattern of changes in its chemical stress. The results of the study will help to understand the effects of mechanical and chemical stresses and combined stresses on CF parameters of weeds and serve as a guide for efficient weed control operations and conducting weed control in the future.

9.
Oncol Rep ; 50(1)2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37203394

RESUMO

Forkhead box D1 (FOXD1) serves a critical role in colorectal cancer (CRC). FOXD1 expression is an independent prognostic factor in patients with CRC; however, the molecular mechanism and signaling pathway of FOXD1 that regulates cell stemness and chemoresistance has not been fully characterized. The aim of the present study was to further validate the effect of FOXD1 on the proliferation and migration of CRC cells, and to delve into the possible potential of FOXD1 in the clinical treatment of CRC. The effect of FOXD1 on cell proliferation was assessed using Cell Counting Kit 8 (CCK­8) and colony formation assays. The effect of FOXD1 on cell migration was assessed by wound­healing and Transwell assays. The effect of FOXD1 on cell stemness was assessed by spheroid formation in vitro and limiting dilution assays in vivo. The expression of stemness associated proteins, leucine rich repeat containing G protein­coupled receptor 5 (LGR5), OCT4, Sox2 and Nanog, and epithelial­mesenchymal transition associated proteins, E­cadherin, N­cadherin and vimentin, were detected by western blotting. Proteins interrelationships were assessed by a co­immunoprecipitation assay. Oxaliplatin resistance was assessed using CCK­8 and apoptosis assays in vitro, and using a tumor xenograft model in vivo. By constructing FOXD1 overexpression and knockdown stably transfected strains of colon cancer cells, it was revealed that the overexpression of FOXD1 increased CRC cell stemness and chemoresistance. By contrast, knockdown of FOXD1 produced the opposite effects. These phenomena were caused by the direct interaction between FOXD1 and ß­catenin, thus promoting its nuclear translocation and the activation of downstream target genes, such as LGR5 and Sox2. Notably, inhibition of this pathway with a specific ß­catenin inhibitor (XAV­939) could impair the effects induced by the overexpression of FOXD1. In summary, these results indicated that FOXD1 may promote cell stemness and the chemoresistance of CRC by binding directly to ß­catenin and enhancing ß­catenin nuclear localization; therefore, it may be considered a potential clinical target.


Assuntos
Neoplasias Colorretais , Fatores de Transcrição Forkhead , beta Catenina , Humanos , beta Catenina/genética , beta Catenina/metabolismo , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Fatores de Transcrição Forkhead/genética , Fatores de Transcrição Forkhead/metabolismo , Regulação Neoplásica da Expressão Gênica , Oxaliplatina/farmacologia , Transdução de Sinais , Via de Sinalização Wnt/genética
10.
Org Biomol Chem ; 21(18): 3784-3788, 2023 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-37092356

RESUMO

An N-heterocyclic carbene-catalyzed cascade [3 + 2 + 1] annulation to assemble vinyl azides, aldehydes, and trihalomethyl reagents (Togni's reagent or CCl4) towards 1,3-oxazin-6-ones was reported. The cascade was triggered by an NHC-catalyzed single electron transfer (SET) between aldehydes and trihalomethyl reagents, followed by the addition of trihalomethyl radicals to vinyl azides, a denitrogenated transformation into iminyl radicals, a C-N radical coupling of iminyl radicals and ketyl radicals, and a base-controlled dehalogenative cyclization.

11.
Front Immunol ; 14: 1175513, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37063892

RESUMO

Introduction: The role of tumour secretory cytokines and peripheral circulatory cytokines in tumour progression has received increasing attention; however, the role of tumour-related inflammatory cytokines in colorectal cancer (CRC) remains unclear. In this study, the concentrations of various cytokines in the peripheral blood of healthy controls and patients with CRC at different stages were compared. Methods: Peripheral blood samples from 4 healthy participants and 22 colorectal cancer patients were examined. Luminex beads were used to evaluate concentration levels of 40 inflammatory cytokines in peripheral blood samples. Results: In peripheral blood, compared with healthy controls and early stage (I + II) CRC patients, advanced CRC (III + IV) patients had increased concentrations of mononuclear/macrophage chemotactic-related proteins (CCL7, CCL8, CCL15, CCL2, and MIF), M2 polarization-related factors (IL-1ß, IL-4), neutrophil chemotactic and N2 polarization-related cytokines (CXCL2, CXCL5, CXCL6, IL-8), dendritic cells (DCs) chemotactic-related proteins (CCL19, CCL20, and CCL21), Natural killer (NK) cell related cytokines (CXCL9, CXCL10), Th2 cell-related cytokines (CCL1, CCL11, CCL26), CXCL12, IL-2, CCL25, and CCL27, and decreased IFN-γ and CX3CL1 concentrations. The differential upregulation of cytokines in peripheral blood was mainly concentrated in CRC patients with distant metastasis and was related to the size of the primary tumour; however, there was no significant correlation between cytokine levels in peripheral blood and the propensity and mechanism of lymph node metastasis. Discussion: Different types of immune cells may share the same chemokine receptors and can co-localise in response to the same chemokines and exert synergistic pro-tumour or anti-tumour functions in the tumour microenvironment. Chemokines and cytokines affect tumour metastasis and prognosis and may be potential targets for treatment.


Assuntos
Neoplasias Colorretais , Citocinas , Humanos , Citocinas/metabolismo , Macrófagos/metabolismo , Neoplasias Colorretais/patologia , Microambiente Tumoral
12.
J Neurosci ; 43(8): 1387-1404, 2023 02 22.
Artigo em Inglês | MEDLINE | ID: mdl-36693757

RESUMO

Developing spinal circuits generate patterned motor outputs while many neurons with high membrane resistances are still maturing. In the spinal cord of hatchling frog tadpoles of unknown sex, we found that the firing reliability in swimming of inhibitory interneurons with commissural and ipsilateral ascending axons was negatively correlated with their cellular membrane resistance. Further analyses showed that neurons with higher resistances had outward rectifying properties, low firing thresholds, and little delay in firing evoked by current injections. Input synaptic currents these neurons received during swimming, either compound, unitary current amplitudes, or unitary synaptic current numbers, were scaled with their membrane resistances, but their own synaptic outputs were correlated with membrane resistances of their postsynaptic partners. Analyses of neuronal dendritic and axonal lengths and their activities in swimming and cellular input resistances did not reveal a clear correlation pattern. Incorporating these electrical and synaptic properties into a computer swimming model produced robust swimming rhythms, whereas randomizing input synaptic strengths led to the breakdown of swimming rhythms, coupled with less synchronized spiking in the inhibitory interneurons. We conclude that the recruitment of these developing interneurons in swimming can be predicted by cellular input resistances, but the order is opposite to the motor-strength-based recruitment scheme depicted by Henneman's size principle. This form of recruitment/integration order in development before the emergence of refined motor control is progressive potentially with neuronal acquisition of mature electrical and synaptic properties, among which the scaling of input synaptic strengths with cellular input resistance plays a critical role.SIGNIFICANCE STATEMENT The mechanisms on how interneurons are recruited to participate in circuit function in developing neuronal systems are rarely investigated. In 2-d-old frog tadpole spinal cord, we found the recruitment of inhibitory interneurons in swimming is inversely correlated with cellular input resistances, opposite to the motor-strength-based recruitment order depicted by Henneman's size principle. Further analyses showed the amplitude of synaptic inputs that neurons received during swimming was inversely correlated with cellular input resistances. Randomizing/reversing the relation between input synaptic strengths and membrane resistances in modeling broke down swimming rhythms. Therefore, the recruitment or integration of these interneurons is conditional on the acquisition of several electrical and synaptic properties including the scaling of input synaptic strengths with cellular input resistances.


Assuntos
Interneurônios , Natação , Animais , Natação/fisiologia , Xenopus laevis/fisiologia , Larva/fisiologia , Reprodutibilidade dos Testes , Interneurônios/fisiologia , Medula Espinal/fisiologia
13.
J Hum Genet ; 68(1): 11-16, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36316471

RESUMO

The vast majority of epidemiological studies suggested a link between systemic lupus erythematosus (SLE) and major depressive disorder (MDD). However, the causality for SLE on the risk of MDD remained unknown due to confounding factors or reverse causality. Herein, we investigated the causality between SLE and MDD in those of European ancestry by a Mendelian randomization (MR) approach. Summary genetic data of cases with SLE/MDD were derived from independent largest public genome-wide association study. Forty-six single nucleotide polymorphisms associated with SLE were used as instrumental variables. The main causal inference was carried out using the MRE-IVW method. Additional, reverse-direction MR and multivariable MR analyses were further performed. Result indicated that SLE was causally associated with a lower risk of MDD (using the MRE-IVW method, odds ratio [OR] = 0.983, 95% confidence interval [CI] = 0.974-0.991, p = 1.18 × 10-4). Complementary analysis found no heterogeneity or horizontal pleiotropy. Multivariate MR analysis yielded consistent results (OR = 0.981; 95% CI = 0.969-0.993; p = 2.75 × 10-3). Reverse-direction MR analysis suggested non-causal relationship of MDD on the risk of SLE (using the IVW method, OR = 0.846, 95% CI = 0.345-2.072; p = 0.714). Thus, this is the first study providing evidence of potential causal links between SLE and MDD and further related research is needed.


Assuntos
Transtorno Depressivo Maior , Lúpus Eritematoso Sistêmico , Humanos , Transtorno Depressivo Maior/epidemiologia , Transtorno Depressivo Maior/genética , Análise da Randomização Mendeliana/métodos , Estudo de Associação Genômica Ampla , Causalidade , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/epidemiologia , Lúpus Eritematoso Sistêmico/genética , Polimorfismo de Nucleotídeo Único
14.
Eur J Clin Invest ; 53(3): e13894, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36256472

RESUMO

BACKGROUND: The causal inference between leisure sedentary behaviour (LSB) and rheumatoid arthritis (RA) is still controversial because of potential residual confounding and reverse causality. METHODS: The present study used publicly available large-scale genome-wide association studies (GWAS) of LSB (television watching, computer use, and driving) and RA to perform a two-sample Mendelian randomization (MR) study to evaluate the causal effect of LSB on the risk of RA. We detected significant causal associations using the multiplicative random effects-inverse variance weighted (MRE-IVW) method, the maximum likelihood, robust adjusted profile scores, the weighted median, MR-Egger regression, and several complementary sensitivity analyses. Risk factor analysis was also conducted to further investigate potential mediators linking causal inference. RESULTS: Increased genetic liability to leisure television watching was significantly associated with a higher risk of RA (MRE-IVW method; OR = 2.46, 95% CI 1.77-3.41; p = 8.35 × 10-8 ). MR estimates indicated that prolonged leisure computer use was causally associated with a lower risk of RA (MRE-IVW method; OR = 0.23, 95% CI 0.12-0.46; p = 2.19 × 10-5 ). However, we found no evidence for a causal effect of leisure driving on the risk of RA (MRE-IVW method; OR = 0.59, 95% CI 0.10-3.41; p = 0.557). No pleiotropy was detected by the sensitivity analysis. CONCLUSIONS: This study supports a causal association between prolonged leisure television watching and an increased risk of RA. Additionally, prolonged computer use might be a protective factor for RA.


Assuntos
Artrite Reumatoide , Comportamento Sedentário , Humanos , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Polimorfismo de Nucleotídeo Único , Artrite Reumatoide/etiologia , Artrite Reumatoide/genética , Fatores de Risco
15.
J Ethnopharmacol ; 300: 115689, 2023 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-36096349

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Xiao Chai Hu Tang (XCHT) derived from the classic medical book Shang Han Lun (Treatise on Febrile Diseases) in the Eastern Han Dynasty, which has been widely used in China and other Asian countries for the treatment of inflammation and fibrosis of chronic pancreatitis (CP), but the therapeutic mechanism of XCHT in pancreatic fibrosis remains unclear. AIM OF THE STUDY: This study aimed to evaluate the intervention effects and explore pharmacological mechanism of XCHT on inflammation and fibrosis in cerulein-induced CP model. MATERIALS AND METHODS: Fifty male C57BL/6 mice were randomly divided into five main groups, 10 animals in each: Control, CP model (50 µg/kg cerulein), high dose XCHT-treated CP group (60 g/kg XCHT), medium dose XCHT-treated CP group (30 g/kg XCHT) and low dose XCHT-treated CP group (15 g/kg XCHT). Different doses of XCHT were given to mice by gavage twice a day for 2 weeks after the CP model induction. Pancreatic tissues were harvested and the pancreatic inflammation and fibrosis were evaluated by histological score, Sirius red staining, and alpha-smooth muscle actin (α-SMA) immunohistochemical staining. ELISA, IHC and RT-qPCR were performed to detect the expression of Vitamin D3 (VD3) and Vitamin D receptor (VDR) in serum and pancreatic tissues, respectively. The expressions of NLRP3 inflammasome related genes and molecules were assayed by WB, IHC and RT-qPCR. RESULTS: The pathohistological results demonstrated that XCHT markedly inhibited the fibrosis and chronic inflammation of cerulein-induced CP, indicated by reduction of collagen I, collagen III, α-SMA, and NLRP3 expressions. XCHT significantly increased VD3 and VDR expression while reduced the pancreatic NLRP3 expression. Correspondingly, XCHT decreased the levels of NLRP3 downstream targets IL-1ß, TNF-α and IL-6. CONCLUSIONS: These results revealed that XCHT suppressed the pancreatic fibrosis and chronic inflammation in cerulein-induced CP model by enhancing the VD3/VDR expression and inhibiting the secretion of NLRP3-assoicated inflammatory factors.


Assuntos
Ceruletídeo , Pancreatite Crônica , Actinas/metabolismo , Animais , Ceruletídeo/efeitos adversos , Colágeno/metabolismo , Modelos Animais de Doenças , Fibrose , Inflamassomos/metabolismo , Inflamação , Interleucina-6 , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Pancreatite Crônica/induzido quimicamente , Pancreatite Crônica/tratamento farmacológico , Pancreatite Crônica/metabolismo , Receptores de Calcitriol/uso terapêutico , Transdução de Sinais , Fator de Necrose Tumoral alfa , Vitamina D/efeitos adversos
16.
J Interv Med ; 5(3): 138-142, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36317150

RESUMO

Objectives: To evaluate the safety and efficacy of balloon-occluded retrograde transvenous obliteration (BRTO) using lauromacrogol sclerosant foam for gastric varices (GVs) with gastrorenal venous shunts. Methods: Data of GV patients treated with BRTO using lauromacrogol sclerosant foam in 2016-2020 were retrospectively analyzed along with procedural success rate, complications, and follow-up efficacy. Results: A total of 31 patients were treated with BRTO. The sclerosant foam was prepared by mixing iodinated oil, lauromacrogol, and air at a 1:2:3 ratio. The BRTO procedure was successfully completed in 93.5% of patients. One patient was allergic to the lauromacrogol injection. A mild postoperative fever occurred in three patients. One patient experienced grand mal seizures after the procedure. There was no significant difference in the median Child-Turcotte-Pugh scores before versus after BRTO. Complete GV resolution was observed in 93.1% of patients. One patient underwent endoscopic treatment for the development of high-risk esophageal varices. Another patient underwent transjugular intrahepatic portosystemic shunt placement for the aggravation of ascites. Conclusions: Lauromacrogol sclerosant foam is safe and effective in patients undergoing BRTO for GV.

17.
Sensors (Basel) ; 22(19)2022 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-36236326

RESUMO

Currently, integrated humidity sensors with fast-response time are widely needed. The most commonly used polyimide capacitive humidity sensor has a long response time, which is difficult to meet the need for a fast response. Most studies focusing on technology and materials have a high cost and are difficult to ensure compatability with the CMOS process. The dynamic compensation method can shorten the response time by only adding digital circuits or software processing. However, conventional compensation technology is not suitable for humidity sensors due to temperature coupling. This paper proposes a new dynamic compensation method for humidity sensors based on the decoupling of temperature factors by analyzing the coupling relationship between sensor dynamic characteristics and temperature. Simulations and experiments were used to verify the proposed method. The experimental results show that the proposed method reduces the humidity response time of the sensor by 85.6%. The proposed method can effectively shorten the response time of humidity sensors.

18.
Nat Commun ; 13(1): 4825, 2022 08 16.
Artigo em Inglês | MEDLINE | ID: mdl-35974004

RESUMO

Major depressive disorder is one of the most common mental health conditions. Meningeal lymphatics are essential for drainage of molecules in the cerebrospinal fluid to the peripheral immune system. Their potential role in depression-like behaviour has not been investigated. Here, we show in mice, sub-chronic variable stress as a model of depression-like behaviour impairs meningeal lymphatics in females but not in males. Manipulations of meningeal lymphatics regulate the sex difference in the susceptibility to stress-induced depression- and anxiety-like behaviors in mice, as well as alterations of the medial prefrontal cortex and the ventral tegmental area, brain regions critical for emotional regulation. Together, our findings suggest meningeal lymphatic impairment contributes to susceptibility to stress in mice, and that restoration of the meningeal lymphatics might have potential for modulation of depression-like behaviour.


Assuntos
Transtorno Depressivo Maior , Vasos Linfáticos , Animais , Feminino , Sistema Linfático , Vasos Linfáticos/fisiologia , Masculino , Meninges , Camundongos , Caracteres Sexuais , Estresse Psicológico
19.
Nat Commun ; 13(1): 3827, 2022 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-35780238

RESUMO

Oxidative carbene organocatalysis, inspired from Vitamin B1 catalyzed oxidative activation from pyruvate to acetyl coenzyme A, have been developed as a versatile synthetic method. To date, the α-, ß-, γ-, δ- and carbonyl carbons of (unsaturated)aldehydes have been successfully activated via oxidative N-heterocyclic carbene (NHC) organocatalysis. In comparison with chemical redox or photoredox methods, electroredox methods, although widely used in mechanistic study, were much less developed in NHC catalyzed organic synthesis. Herein, an iodide promoted electroredox NHC organocatalysis system was developed. This system provided general solutions for electrochemical single-electron-transfer (SET) oxidation of Breslow intermediate towards versatile transformations. Radical clock experiment and cyclic voltammetry results suggested an anodic radical coupling pathway.


Assuntos
Iodetos , Metano , Aldeídos , Metano/análogos & derivados , Regiões Promotoras Genéticas
20.
J Cell Mol Med ; 26(12): 3471-3482, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35579380

RESUMO

Colorectal cancer (CRC) is a worldwide disease with worse survival. Our objective is to identify previously unrecognized prognostic factors to better evaluate disease progression. Seven GEO datasets were collected and analysed using R software, followed by KEGG enrichment analysis and TFs network construction. LASSO-COX analysis was performed to select the most useful prognostic features. COX model was used to analyse prognostic factors associated with OS. The survival curve was constructed using Kaplan-Meier analysis. A Nomogram model was also constructed to predict prognosis. A total of 3559 differentially expressed genes (DEGs) and 66 differentially expressed transcription factors were identified. FOXD1 was identified as the most differentially expressed factor of TFs covering the most downstream DEGs and independent risk prognostic factor. Next, FOXD1 expression was detected using immunohistochemical staining in 131 CRC patients' tissue and the association between FOXD1 expression and clinicopathologic features was analysed. High expression of FOXD1 was correlated with TNM stage and pathological differentiation. Multivariate COX regression analyses confirmed that FOXD1 high-expression, TNM stage and tumour differentiation were independent prognostic risk factor of OS and DFS. Patients with high expression of FOXD1 were more likely to have poor overall survival and disease-free survival. The combination of FOXD1 and Plk2 which we have previously reported allowed us to predict the survival of post-surgical CRC patients more accurately, adding to the former prognostic model based on the TNM Stage. The results showed that patients with high expression of both FOXD1 and Plk2 have the worst survival. A combination of FOXD1 and Plk2 can better evaluate patients' survival.


Assuntos
Neoplasias Colorretais , Fatores de Transcrição Forkhead , Proteínas Serina-Treonina Quinases , Biomarcadores Tumorais/metabolismo , Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Intervalo Livre de Doença , Fatores de Transcrição Forkhead/biossíntese , Fatores de Transcrição Forkhead/genética , Fatores de Transcrição Forkhead/metabolismo , Humanos , Estimativa de Kaplan-Meier , Valor Preditivo dos Testes , Prognóstico , Modelos de Riscos Proporcionais , Proteínas Serina-Treonina Quinases/biossíntese , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/metabolismo
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