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1.
Carbohydr Polym ; 301(Pt A): 120292, 2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-36436850

RESUMO

In order to explore the contributions of hemicelluloses to the assembly and mechanical properties of cellulose networks, the bacterial cellulose (BC) composites containing xylan and glucomannan were prepared to mimic the polysaccharides network of plant cell walls. Both polysaccharides could induce the change of diameters of cellulose ribbons and influence the crystallization of cellulose. Besides, small-angle X-ray scattering (SAXS) demonstrated that xylan inhibited the assembly of microfibrils into cellulose ribbons, while glucomannan promoted the packing of microfibrils. The changes of cellulose crystalline structure and assembly pattern of cellulose contributed to the lower tensile strength and higher strain at break of the BC composites as compared with the BC. The results provide a profound insight into the structure-property relationships of cellulose networks affected by hemicelluloses, which could be conducive to the development of cellulose biomaterials.


Assuntos
Celulose , Xilanos , Celulose/química , Xilanos/química , Espalhamento a Baixo Ângulo , Difração de Raios X , Polissacarídeos/química , Bactérias/química
2.
J Nutr Biochem ; 111: 109178, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36228974

RESUMO

Dysregulated production of peptide hormones is the key pathogenic factor of various endocrine diseases. Endoplasmic reticulum (ER) associated degradation (ERAD) is a critical machinery in maintaining ER proteostasis in mammalian cells by degrading misfolded proteins. Dysfunction of ERAD leads to maturation defect of many peptide hormones, such as provasopressin (proAVP), which results in the occurrence of Central Diabetes Insipidus. However, drugs targeting ERAD to regulate the production of peptide hormones are very limited. Herbal products provide not only nutritional sources, but also alternative therapeutics for chronic diseases. Virtual screening provides an effective and high-throughput strategy for identifying protein structure-based interacting compounds extracted from a variety of dietary or herbal sources, which could be served as (pro)drugs for preventing or treating endocrine diseases. Here, we performed a virtual screening by directly targeting SEL1L of the most conserved SEL1L-HRD1 ERAD machinery. Further, we analyzed 58 top-ranked compounds and demonstrated that Cryptochlorogenic acid (CCA) showed strong affinity with the binding pocket of SEL1L with HRD1. Through structure-based docking, protein expression assays, and FACS analysis, we revealed that CCA enhanced ERAD activity and promoted the degradation of misfolded proAVP, thus facilitated the secretion of well-folded proAVP. These results provide us with insights into drug discovery strategies targeting ER protein homeostasis, as well as candidate compounds for treating hormone-related diseases.


Assuntos
Degradação Associada com o Retículo Endoplasmático , Hormônios Peptídicos , Animais , Retículo Endoplasmático/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Proteínas/metabolismo , Hormônios Peptídicos/metabolismo , Mamíferos/metabolismo
3.
J Ethnopharmacol ; 302(Pt A): 115761, 2023 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-36309113

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Houttuynia cordata Thunb. (HC, Saururaceae family) is a classical Traditional Chinese Medicine used to treat pneumonia clinically. The total flavonoids (HCF) and polysaccharides (HCP) are key medicinal components of H. cordata involved in its beneficial effect on viral pneumonia. AIM OF THE STUDY: The purpose of the study is to investigate the synergistic or complementary effects of combination of HCF and HCP on viral pneumonia as well as the mechanisms underlying. MATERIALS AND METHODS: HCF or HCP were administrated separately or combined in different proportions on influenza virus H1N1 - infected mice. The survival and lung weight of mice were recorded. The synergistic effect on HCF and HCP combination was calculated by Chou-Talalay method. H&E staining was performed to detect lung histomorphology. Western blot, immunohistochemistry and enzyme linked immunosorbent assay were done to analyze the representative protein expression in lung and intestine tissues. AB - PAS staining on intestine tissue sections was performed to evaluate the histopathology of intestines. Bacterial genomic DNA was extracted and sequenced for gut microbiota analysis. RESULTS: In H1N1 lethally infected mice, the combined administration of HCF and HCP significantly increased the survival rate and prolonged the life span of mice, compared with mono-drug therapy. The viral pneumonia was remarkably improved by HCF and HCP combination reflected by lower lung index, more intact lung morphology, and less inflammatory cells and mediators. Furthermore, the combination of HCF and HCP regulated intestinal microbiota, significantly reduced the proportion of pathogenic Proteobacteria and the secretion of proinflammatory cytokine in gut. The combined HCF and HCP showed synergistic effect on reducing lung and intestine injury. The complementary interaction was also found in HCF and HCP combined therapy, as HCF provided the significant antiviral activity and HCP markedly improved intestinal physical barrier and increased the protein expression involving removal of edema. CONCLUSIONS: Our findings indicated that combination of HCF and HCP from H. cordata synergistically alleviated H1N1-induced viral pneumonia in mice via multimodal regulation of both pulmonary and intestinal homeostasis, which might imply novel therapeutic strategy for treating viral pneumonia.

4.
J Pharm Biomed Anal ; 223: 115158, 2023 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-36410130

RESUMO

In the present study, a procyanidins-enriched fraction (PCE) from the rhizome of Fagopyrum dibotrys was obtained by anticomplement activity-guided fractionation. PCE could alleviate H1N1-induced ALI in mice by reducing weight loss, decreasing lung index, and regulating cytokine levels in lung tissue. PCE contained 76.5 ± 1.1% procyanidins with a mean degree of polymerization (mDP) of 5.24 ± 0.16. Meanwhile, thirty-three chemical constituents, including 27 procyanidins and 6 other compounds, were recognized by UPLC-Triple-TOF-MS/MS. Among them, twenty recognized procyanidins were composed of (epi)catechin with B-type link, while the rest consisted of (epi)catechin gallate. Furthermore, six compounds were obtained by preparative HPLC on a C18 column (250 × 10.0 mm, 5 µm), and their structures were confirmed by mass spectrum (MS), nuclear magnetic resonance (NMR), and specific rotation. The structure-activity relationship analysis indicated that DP and galloylation were closely related to the anticomplement activity of procyanidins. The obtained results revealed that anticomplement procyanidins were one kind of the potentially effective materials of F. dibotrys against H1N1 influenza virus infection, and the in vivo efficacy of these compounds was worthy of further investigation.


Assuntos
Lesão Pulmonar Aguda , Fagopyrum , Vírus da Influenza A Subtipo H1N1 , Influenza Humana , Proantocianidinas , Animais , Camundongos , Humanos , Proantocianidinas/farmacologia , Proantocianidinas/uso terapêutico , Espectrometria de Massas em Tandem , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/tratamento farmacológico
5.
Front Cell Dev Biol ; 10: 978962, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36393848

RESUMO

Early embryonic cell cycles usually alternate between S and M phases without any gap phase. When the gap phases are developmentally introduced in various cell types remains poorly defined especially during embryogenesis. To establish the cell-specific introduction of gap phases in embryo, we generate multiple fluorescence ubiquitin cell cycle indicators (FUCCI) in C. elegans. Time-lapse 3D imaging followed by lineal expression profiling reveals sharp and differential accumulation of the FUCCI reporters, allowing the systematic demarcation of cell cycle phases throughout embryogenesis. Accumulation of the reporters reliably identifies both G1 and G2 phases only in two embryonic cells with an extended cell cycle length, suggesting that the remaining cells divide either without a G1 phase, or with a brief G1 phase that is too short to be picked up by our reporters. In summary, we provide an initial picture of gap phase introduction in a metazoan embryo. The newly developed FUCCI reporters pave the way for further characterization of developmental control of cell cycle progression.

6.
Front Oncol ; 12: 987518, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36419882

RESUMO

Purpose: Recent studies have revealed the contrasting prognostic roles of body mass index (BMI) and tumor location in colorectal cancer (CRC). Given that right- and left-sided CRC may exhibit inverse effects on outcome and body weight, the present study aimed to examine whether the prognostic value of BMI and tumor location could be reciprocally stratified. Methods: This prospective, observational study recruited 4,086 patients diagnosed with stage III CRC from five independent clinical centers in China. The association of patients' outcomes with BMI and tumor location was evaluated hierarchically by Kaplan-Meier and Cox proportional-hazards models. Results: Although BMI was not associated with overall outcome, the association was significantly modified by tumor location. Among left-sided tumors, obesity and overweight were significantly associated with adverse overall survival (OS) and disease-specific survival (DSS). In contrast, among right-sided tumors, overweight was significantly associated with more favorable OS and DSS compared with the normal-weight group. The association of survival with tumor location did not reach statistical significance. However, hierarchical analysis by BMI revealed that left-sided tumors were associated with more favorable outcomes in the normal-weight group, while there was no statistically significant difference in the overweight or obese group. Conclusions: BMI and tumor location may have opposing effects on CRC prognosis, when stratified by each other, after adjusting for other known prognostic factors. These findings are the first to show the interactive prognostic impact of BMI and tumor location, which could be relevant to the stratification of patient management.

7.
Front Oncol ; 12: 1019153, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36419894

RESUMO

Copper is an essential trace element in an organism, and changes in copper levels in vivo often indicate a diseased state. Copper and immunity have been discussed since the last century, with copper deficiency significantly affecting the development and function of the immune system, such as increased host susceptibility to various pathogens, decreased number and impaired function of neutrophils, reduced antibacterial activity of macrophages, decreased proliferation of splenocytes, impaired B cell ability to produce antibodies and impaired function of cytotoxic T lymphocyte and helper T cells. In the past 20 years, some studies have shown that copper ions are related to the development of many tumors, including lung cancer, acute lymphoid leukaemia, multiple myeloma and other tumors, wherein copper ion levels were significantly elevated, and current studies reveal that copper ions are involved in the development, growth and metastasis of tumors through various pathways. Moreover, recent studies have shown that copper ions can regulate the expression of PD-L1, thus, attention should be paid to the important role of copper in tumor immunity. By exploring and studying copper ions and tumor immunity, new insights into tumor immunity could be generated and novel therapeutic approaches to improve the clinical prognosis of patients can be provided.

8.
Front Immunol ; 13: 1009530, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36389762

RESUMO

Tetrastigma hemsleyanum Diels et Gilg is a traditional Chinese herbal medicine with high medicinal value, and antitumor, antioxidant and anti-inflammatory biological activities. However, while several studies have focused on flavonoids in Tetrastigma hemsleyanum tubers, there are few studies on the enhanced immune effect of Tetrastigma hemsleyanum polysaccharides (THP). In this study, we evaluated the antitumor effect of THP in a lung tumor model and explored the mechanism of antitumor activity through intestinal flora. In addition, a cyclophosphamide (CTX)-induced immunosuppression model was used to declare the immunomodulatory effect of THP in the immunosuppressive state induced by antitumor drugs. The results showed that THP increased the content of ileum secreted immunoglobulin A (SIgA) and cecum short-chain fatty acids (SCFAs) and improved microbial community diversity, regulating the relative abundance of dominant microbiota flora from the phylum level to the genus level, and recovering the intestinal microflora disorder caused by tumors. Additionally, THP can increase the organ indices and improve immune organ atrophy. THP can upregulate routine blood counts and stimulate the production of the serum cytokines. THP also promoted the macrophage phagocytic index, NK-cell activation, and complement and immunoglobulin (IgG, IgA, IgM) levels. The detection of Splenic lymphocyte proliferation and T lymphocyte subsets also sideways reflects that THP can restore CTX-induced immune inhibition in mice. In conclusion, this study suggests that THP can effectively achieve the enhanced antitumor effects, regulate gut microbiota and improve the immunosuppression induced by antitumor drugs. Therefore, THP can enhance the immune capacity and provide novel immunomodulatory and antineoplastic adjuvant agents.


Assuntos
Microbioma Gastrointestinal , Vitaceae , Camundongos , Animais , Polissacarídeos/farmacologia , Polissacarídeos/uso terapêutico , Imunidade , Imunomodulação
9.
Front Cardiovasc Med ; 9: 995275, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36407434

RESUMO

Background: Ventricular septal rupture (VSR) is a type of cardiac rupture, usually complicated by acute myocardial infarction (AMI), with a high mortality rate and often poor prognosis. The aim of our study was to investigate the factors influencing the long-term prognosis of patients with VSR from different aspects, comparing the evaluation performance of the Gensini score, Sequential Organ Failure Assessment (SOFA) score and European Heart Surgery Risk Assessment System II (EuroSCORE II) score systems. Methods: This study retrospectively enrolled 188 patients with VSR between Dec 9, 2011 and Nov 21, 2021at the First Affiliated Hospital of Zhengzhou University. All patients were followed up until Jan 27, 2022 for clinical data, angiographic characteristics, echocardiogram outcomes, intraoperative, postoperative characteristics and major adverse cardiac events (MACEs) (30-day mortality, cardiac readmission). Cox proportional hazard regression analysis was used to explore the predictors of long-term mortality. Results: The median age of 188 VSR patients was 66.2 ± 9.1 years and 97 (51.6%) were males, and there were 103 (54.8%) patients in the medication group, 34 (18.1%) patients in the percutaneous transcatheter closure (TCC) group, and 51 (27.1%) patients in the surgical repair group. The average follow-up time was 857.4 days. The long-term mortality of the medically managed group, the percutaneous TCC group, and the surgical repair group was 94.2, 32.4, and 35.3%, respectively. Whether combined with cardiogenic shock (OR 0.023, 95% CI 0.001-0.054, P = 0.019), NT-pro BNP level (OR 0.027, 95% CI 0.002-0.34, P = 0.005), EuroSCORE II (OR 0.530, 95% CI 0.305-0.918, P = 0.024) and therapy group (OR 3.518, 95% CI 1.079-11.463, P = 0.037) were independently associated with long-term mortality in patients with VSR, and this seems to be independent of the therapy group. The mortality rate of surgical repair after 2 weeks of VSR was much lower than within 2 weeks (P = 0.025). The cut-off point of EuroSCORE II was determined to be 14, and there were statistically significant differences between the EuroSCORE II < 14 group and EuroSCORE II≥14 group (HR = 0.2596, 95%CI: 0.1800-0.3744, Logrank P < 0.001). Conclusion: Patients with AMI combined with VSR have a poor prognosis if not treated surgically, surgical repair after 2 weeks of VSR is a better time. In addition, EuroSCORE II can be used as a scoring system to assess the prognosis of patients with VSR.

10.
J Biol Chem ; : 102678, 2022 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-36356901

RESUMO

Metformin, an antidiabetic drug, shows some potent anti-tumor effects. However, the molecular mechanism of metformin in tumor suppression has not been clarified. Here we provided evidence using in vitro and in vivo data that metformin inhibited mevalonate pathway by downregulation of HMGCS1, a key enzyme in this pathway. Our results further demonstrated that metformin downregulated HMGCS1 expression through inhibition of transcription factor NRF2. Additionally, we determined that HMGCS1 was highly expressed in human liver and lung cancer tissues and associated with lower survival rates. In summary, our study indicated that metformin suppresses tumorigenesis through inhibition of the NRF2/HMGCS1 axis, which might be a potential target in cancer prevention and treatment.

11.
Animal Model Exp Med ; 2022 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-36369766

RESUMO

Pancreatic ductal adenocarcinoma (PDAC) is a highly malignant cancer of the digestive system common among humans. However, it is rarely reported in wild animals. In 2018, a giant panda died in the Beijing Zoo. During subsequent histological observation of the pancreas, it was discovered that the glandular epithelial cells had lost the pancreatic acinar structure, tubular areas with obvious structure in the pancreas, and the ductal epithelium was substituted by high columnar mucus cells. Masson staining showed that there were several fibrous tissue proliferative reactions around the ductal adenocarcinoma and immunohistochemical staining revealed that CK7 and CK19 were positively expressed in the pancreatic tissue. Therefore, the pathological diagnosis indicated that the panda had PDAC. In this paper, the panda's living conditions and pathological diagnosis results are examined, with the aim of providing a reference point for the future diagnosis of wild animal tumors.

12.
J Nutr Biochem ; : 109213, 2022 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-36370931

RESUMO

Diabetic retinopathy (DR) is one of the most prevalent microvascular complications caused by diabetes mellitus. Previous studies demonstrate that microvascular endothelial inflammation caused by chronic hyperglycemia and hyperlipidemia plays a key role in the pathogenesis of DR. However, the detailed mechanisms on how endothelial inflammation contributes to DR are not fully understood. The STING pathway is an important innate immune signaling pathway. Although STING has been implicated in multiple autoimmune and metabolic diseases, it is not clear whether STING is involved in the pathogenesis of DR. Thus, re-analysis of the public single cell RNA sequencing (sc-RNAseq) data demonstrated that STING was highly expressed in mouse retinal vessels by. Moreover, our results demonstrated that STING and p-TBK1 protein levels in retinal endothelial cells are significantly increased in mice fed with high fat diet compared with chow diet. In vitro, palmitic acid treatment on HRVECs induced mitochondrial DNA leakage into the cytosol, and augmented p-TBK1 protein and IFN-ß mRNA levels. As STING is localized to the ER, we analyzed the relation between STING activation and ER stress. In HRVECs, STING pathway was shown to be activated under chemical-induced ER stress, but attenuated when IRE1α was abolished by genetic deletion or pharmacological inhibition. Taken together, our findings revealed that STING signaling plays an important role in mediating lipotoxicity-induced endothelial inflammatory and injury, and IRE1α-XBP1 signaling potentiated STING signaling. Thus, targeting the IRE1α or STING pathways to alleviate endothelial inflammation provides candidate therapeutic target for treating DR as well as other microvascular complications.

13.
Cell Death Dis ; 13(11): 936, 2022 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-36344495

RESUMO

Long non-coding RNAs (lncRNAs) play key roles in cancer development and progression. However, the biological function and clinical significance of most lncRNAs in cervical cancer remain elusive. In this study, we explore the function and mechanism of lncRNA surfactant associated 1 (SFTA1P) in cervical cancer. We firstly identified SFTA1P by analyzing the RNA sequencing data of cervical cancer from our previous study and from The Cancer Genome Atlas (TCGA). We then verified SFTA1P expression by qRT-PCR. The cell proliferation and migration capacity of SFTA1P was assessed by using CCK-8, colony formation, transwell and wound healing assays. RNA pull-down, RNA immunoprecipitation (RIP), RNA stability and western blot assays were used to reveal potential mechanisms. Athymic nude mice were used to evaluate tumorigenicity and metastasis in vivo. SFTA1P is upregulated in cervical tumor tissues and its high expression is associated with poor prognosis. Biologically, knockdown of SFTA1P inhibited the proliferation, migration, and invasion of cervical cancer cells in vitro, as well as tumorigenesis and metastasis in vivo. Mechanistically, SFTA1P was shown to interact with polypyrimidine tract binding protein 1 (PTBP1) to regulate the stability of tropomyosin 4 (TPM4) mRNA, thereby resulting in malignant cell phenotypes. TPM4 knockdown could attenuate the suppression of cell progression induced by either SFTA1P or PTBP1 knockdown. Our findings demonstrate that SFTA1P can promote tumor progression by mediating the degradation of TPM4 mRNA through its interaction with PTBP1 protein. This provides a potential therapeutic strategy to target the SFTA1P-PTBP1-TPM4 axis in cervical cancer.


Assuntos
RNA Longo não Codificante , Neoplasias do Colo do Útero , Animais , Feminino , Humanos , Camundongos , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Ribonucleoproteínas Nucleares Heterogêneas/genética , Ribonucleoproteínas Nucleares Heterogêneas/metabolismo , Camundongos Nus , Proteína de Ligação a Regiões Ricas em Polipirimidinas/genética , Proteína de Ligação a Regiões Ricas em Polipirimidinas/metabolismo , Estabilidade de RNA/genética , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , RNA Mensageiro/genética , Tropomiosina/genética , Tropomiosina/metabolismo , Neoplasias do Colo do Útero/patologia
14.
Front Oncol ; 12: 973579, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36387106

RESUMO

Background: Extramammary Paget' s disease (EMPD) is a rare cutaneous malignant tumor, and the prognostic factors associated with penoscrotal EMPD remains unclear. The purpose of this study is to investigate prognostic factors and construct nomograms to predict the outcome of patients with EMPD located in the penis or scrotum. Methods: From the Surveillance, Epidemiology and End Results (SEER) database, we extracted 95 patients with primary EMPD located in the penis or scrotum as the training cohort. Forty-nine penoscrotal EMPD patients were included from two medical centers as the external validation cohort. Univariate and multivariate Cox regression model were applied to investigating risk factors of cancer-specific survival (CSS) and overall survival (OS). Based on the results of multivariate Cox regression analysis, the nomograms were constructed for predicting CSS and OS of patients with penoscrotal EMPD. The concordance index (C-index), receiver operating characteristic (ROC) curves and calibration curves were applied to evaluate the practicability and accuracy of the nomograms. Results: In the training cohort, multivariate Cox regression analysis showed that marital status and tumor stage were independent factors of CSS, and marital status, tumor stage and surgery are associated with OS independently in patients with penoscrotal EMPD. Based on these results, we developed nomograms to predict CSS and OS respectively. The C-index values were 0.778 for CSS, and 0.668 for OS in the training set, which displayed the good discriminations. In the external validation set, the C-index values were 0.945 for CSS, and 0.703 for OS. The areas under the curve (AUC) values of nomogram predicting 1-, 3-, and 5-year CSS were 0.815, 0.833, and 0.861 respectively, and 0.839, 0.654, and 0.667 for nomogram predicting 1-, 3-, and 5-year OS respectively. In the validation set, the AUC values of nomogram predicting 1-, 3-, and 5-year CSS were 0.944, 0.896, and 0.896 respectively, and 0.777, 0.762 and 0.692 for nomogram predicting 1-, 3-, and 5-year OS respectively. Additionally, the internal calibration curves also proved that our nomograms have good accuracy. Conclusions: By incorporating marital status, tumor stage and/or surgery, our nomograms can efficiently predict CSS and OS of patients with penoscrotal EMPD.

15.
Insects ; 13(11)2022 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-36354837

RESUMO

Spirodiclofen is one of the most widely used acaricides in China. The citrus red mite, Panonychus citri (McGregor) (Acari: Tetranychidae), is one of the most destructive citrus pests worldwide and has developed a high resistance to spirodiclofen. However, the molecular mechanism of spirodiclofen resistance in P. citri is still unknown. In this study, we identified a field spirodiclofen-resistant strain (DL-SC) that showed 712-fold resistance to spirodiclofen by egg bioassay compared to the susceptible strain. Target-site resistance was not detected as non-synonymous mutations were not found by amplification and sequencing of the ACCase gene of resistant and susceptible strains; in addition, the mRNA expression levels of ACCase were similar in both resistant and susceptible strains. The activity of detoxifying enzymes P450s and CCEs in the resistant strain was significantly higher than in the susceptible strain. The transcriptome expression data showed 19 xenobiotic metabolisms genes that were upregulated. Stage-specific expression profiling revealed that the most prominent upregulated gene, CYP385C10, in transcriptome data was significantly higher in resistant strains in all stages. Furthermore, functional analysis by RNAi indicated that the mortality caused by spirodiclofen was significantly increased by silencing the P450 gene CYP385C10. The current results suggest that overexpression of the P450 gene, CYP385C10, may be involved in spirodiclofen resistance in P. citri.

16.
Nat Commun ; 13(1): 7260, 2022 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-36434066

RESUMO

G-protein-signaling modulator 1 (GPSM1) exhibits strong genetic association with Type 2 diabetes (T2D) and Body Mass Index in population studies. However, how GPSM1 carries out such control and in which types of cells are poorly understood. Here, we demonstrate that myeloid GPSM1 promotes metabolic inflammation to accelerate T2D and obesity development. Mice with myeloid-specific GPSM1 ablation are protected against high fat diet-induced insulin resistance, glucose dysregulation, and liver steatosis via repression of adipose tissue pro-inflammatory states. Mechanistically, GPSM1 deficiency mainly promotes TNFAIP3 transcription via the Gαi3/cAMP/PKA/CREB axis, thus inhibiting TLR4-induced NF-κB signaling in macrophages. In addition, we identify a small-molecule compound, AN-465/42243987, which suppresses the pro-inflammatory phenotype by inhibiting GPSM1 function, which could make it a candidate for metabolic therapy. Furthermore, GPSM1 expression is upregulated in visceral fat of individuals with obesity and is correlated with clinical metabolic traits. Overall, our findings identify macrophage GPSM1 as a link between metabolic inflammation and systemic homeostasis.


Assuntos
Diabetes Mellitus Tipo 2 , Camundongos , Animais , Diabetes Mellitus Tipo 2/metabolismo , Camundongos Endogâmicos C57BL , Macrófagos/metabolismo , Obesidade/metabolismo , Inflamação/metabolismo , Homeostase , Inibidores de Dissociação do Nucleotídeo Guanina/metabolismo
17.
Ir J Med Sci ; 2022 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-36409423

RESUMO

Ovarian Brenner tumor with abnormally increased serum carbohydrate antigen 19-9 (CA19-9) level is extremely rare. A 70-year-old woman with abnormally elevated serum CA199 (1289 U/ml) found in routine physical examination. Pelvic CT and MRI scan revealed a large mass with large patches of calcification in the right adnexal area, and the patient achieved total hysterectomy and bilateral adnexectomy. Grossly, the right ovary had a solid enlargement of about 7.0 cm × 6.0 cm × 5.0 cm with irregular nodules and smooth surface and the cut surface of the mass showed that the tumor is cystic and solid. Microscopically, the tumor showed a background of fibrous tissue hyperplasia with nested and adenoid cell clusters with uniform cell size and clear boundaries. The cells were translucent with eosinophilic cytoplasm and calcification. Immunohistochemical staining showed CK7, CA125, and P63 presented diffusely strongly positive staining, while negativity for CK20, GATA3, AR, P53, and CgA. Ki-67 showed weak positive staining, about 1%. The serum CA199 level decreased significantly on the 5th day after surgery. Postoperative pathology and immunohistochemistry confirmed borderline Brenner tumor. This is the first to report a case of borderline Brenner tumor with an abnormally high serum level of CA199 before surgery. In clinical practice, the possibility of ovarian Brenner tumor should be considered when abnormal elevation of serum CA199 level cannot be reasonably explained.

18.
Molecules ; 27(22)2022 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-36431955

RESUMO

Qingdai-Mabo (QM), a traditional Chinese herbal formula composed of medicinal herb and fungus, has been used for treatment of cough and viral pneumonia. However, the underlying mechanism and bioactive components against anti-influenza A virus remain unclear. In the present study, ethyl acetate (EA) extract of QM decoctions was tested for its biological activity against acute lung injury (ALI) and its main components were identified using UPLC-MS/MS. In total, 18 bioactive components were identified, including 2-Methylquinaozlin-4(3H)-one (C1), which showed significant antiviral activity in vitro with an IC50 of 23.8 µg/mL. Furthermore, we validated the efficacy of C1 in ameliorating ALI lesions and inflammation in influenza A virus-infected mice. The results showed that C1 significantly reduced the lung index, downregulated neuraminidase (NA) and nucleoprotein (NP), and decreased the expression of pro-inflammatory molecules IFN-α, TNF-α, MCP-1, IL-6, and IL-8; however, they enhanced levels of IL-10 and IFN-γ in lung homogenate from mice infected by influenza A virus. In addition, C1 inhibited the recruitment of macrophages. These in vitro and in vivo studies suggested that the significant anti-influenza A virus activity contributed to its curative effect on lesions and inflammation of viral pneumonia in mice. Given its potential antiviral activity against influenza A virus, C1 is determined to be a main active component in the EA extract of QM. Taken together, the antiviral activity of C1 suggests its potential as an effective treatment against viral pneumonia via the inhibition of virus replication, but the mechanism C1 on antiviral research needs to be explored further.


Assuntos
Lesão Pulmonar Aguda , Vírus da Influenza A Subtipo H1N1 , Vírus da Influenza A , Pneumonia Viral , Camundongos , Animais , Antivirais/farmacologia , Antivirais/uso terapêutico , Cromatografia Líquida , Espectrometria de Massas em Tandem , Lesão Pulmonar Aguda/tratamento farmacológico , Inflamação/tratamento farmacológico , Pneumonia Viral/tratamento farmacológico , Extratos Vegetais/farmacologia
19.
Medicine (Baltimore) ; 101(43): e31410, 2022 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-36316839

RESUMO

There are different results on the effect of endotracheal tube (ETT) size on respiratory mechanics in patients undergoing mechanical ventilation, and there are few reports in adult laparoscopic surgery. The aim of this study was to investigate the effect of ETT size on airway resistance (RAW) and dynamic lung compliance (COMPL) in patients undergoing laparoscopic colorectal surgery. Seventy-two patients undergoing laparoscopic radical surgery for colorectal cancer under general anesthesia with endotracheal intubation were selected and divided into 3 groups (n = 24) using the random number table method Group A (ETT ID 7.0), Group B (ETT ID 7.5), and Group C (ETT ID 8.0). After mechanical ventilation, intraoperative RAW and COMPL were monitored in each of the 3 groups. In the non-pneumoperitoneal state, RAW in group ID7.0 is significantly higher than this in group ID7.5 and group ID8.0 (P < .05); the RAW between the 2 groups with ID7.5 and ID8.0 was not statistically significant (P > .05). The difference of COMPL between the 3 groups was statistically significant (P < .05); the COMPL of Group ID7.0 is lower than Group ID7.5, and Group ID7.5 is lower than Group ID8.0. In the pneumoperitoneal state, the RAW between ID7.0 group and ID8.0 group was statistically significant, the RAW difference between ID7.0 group and ID7.5 group, ID7.5 group and ID8.0 group not statistically significant (P > .05);the COMPL between the 3 groups was not statistically significant (P > .05). In the non-pneumoperitoneal state, the smaller the ETT internal diameter within a certain range, the higher RAW and the lower COMPL; in the pneumoperitoneal state, the RAW with the ID7.0 ETT was higher than that with the ID8.0 ETT, and the ETT size within a certain range had no effect on COMPL.


Assuntos
Resistência das Vias Respiratórias , Intubação Intratraqueal , Adulto , Humanos , Complacência Pulmonar , Intubação Intratraqueal/métodos , Respiração Artificial/métodos , Mecânica Respiratória
20.
Front Endocrinol (Lausanne) ; 13: 1018093, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36339429

RESUMO

Background: Gut microbiota has been reported to play an important role in diabetic kidney disease (DKD), however, the alterations of gut bacteria have not been determined. Methods: Studies comparing the differences of gut microbiome between patients with DKD and non-DKD individuals using high-throughput sequencing technology, were systematically searched and reviewed. Outcomes were set as gut bacterial diversity, microbial composition, and correlation with clinical parameters of DKD. Qualitative data were summarized and compared through a funnel R script, and quantitative data were estimated by meta-analysis. Results: A total of 15 studies and 1640 participants were included, the comparisons were conducted between DKD, diabetes mellitus (DM), non-diabetic kidney disease (NDKD), and healthy controls. There were no significant differences of α-diversity between DKD and DM, and between DKD and NDKD, however, significant lower microbial richness was found in DKD compared to healthy controls. Different bacterial compositions were found between DKD and non-DKD subjects. The phylum Actinobacteria were found to be enriched in DKD compared to healthy controls. At the genus level, we found the enrichment of Hungatella, Bilophila, and Escherichia in DKD compared to DM, patients with DKD showed lower abundances of Faecalibacterium compared to those with NDKD. The genera Butyricicoccus, Faecalibacterium, and Lachnospira were depleted in DKD compared to healthy controls, whereas Hungatella, Escherichia, and lactobacillus were significantly enriched. The genus Ruminococcus torques group was demonstrated to be inversely correlated with estimated glomerular filtration rate of DKD. Conclusions: Gut bacterial alterations was demonstrated in DKD, characterized by the enrichment of the genera Hungatella and Escherichia, and the depletion of butyrate-producing bacteria, which might be associated with the occurrence and development of DKD. Further studies are still needed to validate these findings, due to substantial heterogeneity. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42022340870.


Assuntos
Diabetes Mellitus , Nefropatias Diabéticas , Microbioma Gastrointestinal , Humanos , Taxa de Filtração Glomerular , Bactérias , Nível de Saúde
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