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1.
Sci Rep ; 12(1): 7532, 2022 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-35534604

RESUMO

The Indian and Pacific Oceans surround the Maritime Continent (MC). Major modes of sea surface temperature variability in both oceans, including the Indian Ocean Dipole (IOD) and El Niño-Southern Oscillation (ENSO), can strongly affect precipitation on the MC. The prevalence of fires in the MC is closely associated with precipitation amount and terrestrial water storage in September and October. Precipitation and terrestrial water storage, which is a measurement of hydrological drought conditions, are significantly modulated by Indian Ocean Dipole (IOD) and El Niño events. We utilize long-term datasets to study the combined effects of ENSO and the IOD on MC precipitation during the past 100 years (1900-2019) and find that the reductions in MC precipitation and terrestrial water storage are more pronounced during years when El Niño and a positive phase of the IOD (pIOD) coincided. The combined negative effects are produced mainly through an enhanced reduction of upward motion over the MC. Coincident El Niño-pIOD events have occurred more frequently after 1965. However, climate models do not project a higher occurrence of coincident El Niño-pIOD events in a severely warming condition, implying that not the global warming but the natural variability might be the leading cause of this phenomenon.


Assuntos
El Niño Oscilação Sul , Aquecimento Global , Oceano Índico , Oceano Pacífico , Água
2.
Theriogenology ; 187: 119-126, 2022 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-35567989

RESUMO

RNA-seq technology can be used for the detection of miRNA transcripts in tissues and cells at specific periods and under specific treatment conditions, which can easily and effectively screen out differential transcripts. The purpose of this study was to compare miRNA expression in porcine cumulus cells before and after oocyte maturation, and to investigate the mechanism whereby cumulus cells may influence oocyte maturation. To that aim, cumulus cells surrounding GV- and MII-stage oocytes were isolated, and their differences in miRNA expression were examined using miRNA-seq. 143 differentially expressed miRNAs were identified, among which miR-101 was selected and further verified by qPCR. Moreover, miR-101 was found to target HAS2 through target gene prediction, luciferase-based co-transfection and cumulus cells transfection. Transfection of COCs with miR-101 mimics or inhibitor revealed that the miR-101 could inhibit oocyte IVM by regulating the expanding of CCSs, but had no effect on the embryo development competence. These findings demonstrated that miR-101 regulated oocyte maturation in vitro via targeting HAS2 in porcine cumulus cells.

3.
Gland Surg ; 11(4): 742-750, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35531104

RESUMO

Background: Human epidermal growth factor receptor 2 (HER2) inhibitors play a vital role in the treatment of HER2-positive breast cancer. Numerous studies have shown that traditional HER2 inhibitors and chemotherapeutics such as albumin-paclitaxel, liposomal doxorubicin, and cyclophosphamide (TAC regimen) have different degrees of cardiotoxicity. Pyrotinib is a novel small-molecule HER2 inhibitor and has no cardiotoxicity. Here, the purpose of this study was to investigate the cardiac safety of pyrotinib with TAC regimen for HER2-positive breast cancer. Methods: In this study, 22 patients with stage I-IIIA HER2-positive breast cancer were screened, enrolled, and assigned to receive either neoadjuvant or postoperative adjuvant treatment with pyrotinib (320-400 mg, once daily) combined with TAC (albumin-paclitaxel 260 mg/m2, liposomal doxorubicin 20 mg/m2, cyclophosphamide 600 mg/m2) from December 2019 to May 2021. Patients' heart function was monitored using electrocardiogram, echocardiogram, and serological indicators. ST segment and T wave change, left ventricular ejection fraction (LVEF, %), N-terminal pro-B-type natriuretic peptide (NT-pro-BNP), creatine kinase (CK), creatine kinase myoglobin band (CK-MB), together with patients' weight, white blood cells (WBC), red blood cells (RBC), platelets, plasma lipid, and glucose were recorded. Results: Before and after the 2nd, 4th, and 6th cycles of treatment, the incidence of abnormal electrocardiogram of patients enrolled in the neoadjuvant treatment group was 36.4%, 27.3%, 27.3%, and 27.3%, respectively, while in the postoperative adjuvant treatment, the incidence was 45.5%, 36.4%, 36.4%, and 36.4%, respectively. LVEF before and after treatment in the neoadjuvant chemotherapy group was 65.36%±2.25% and 65.00%±2.15% (t=1.305, P=0.221), while in the postoperative adjuvant treatment group, LVEF was 66.27%±2.69% and 65.18%±1.89% (t=1.359, P=0.204). Pyrotinib combined with a TAC regimen may have induced a decrease in RBC. No obvious abnormality was found in the level of NT-pro-BNP, CK, CK-MB, patients' weight, WBC, platelets, plasma lipid, or glucose in all enrolled patients during the entire treatment process. Conclusions: Our findings indicated that neither neoadjuvant nor postoperative adjuvant treatment using pyrotinib combined with a TAC regimen to treat patients with HER2-positive breast cancer increased cardiotoxicity. However, the treatment may have induced a decrease in RBC and further research is needed.

4.
Int J Nanomedicine ; 17: 1851-1864, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35502235

RESUMO

Nano silver is one of the most widely used engineering nanomaterials with antimicrobial activity against bacteria, fungi, and viruses. However, the widespread application of nano silver preparations in daily life raises concerns about public health. Although several review articles have described the toxicity of nano silver to specific major organs, an updated comprehensive review that clearly and systematically outlines the harmful effects of nano silver is lacking. This review begins with the routes of exposure to nano silver and its distribution in vivo. The toxic reactions are then discussed on three levels, from the organ to the cellular and subcellular levels. This review also provides new insights on adjusting the toxicity of nano silver by changing their size and surface functionalization and their combination with other materials to form a composite formulation. Finally, future development, challenges, and research directions are discussed.


Assuntos
Nanopartículas Metálicas , Nanoestruturas , Bactérias , Nanopartículas Metálicas/toxicidade
5.
FASEB J ; 36 Suppl 12022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35556351

RESUMO

Endothelial cell death is an early event in acute lung injury (ALI) leading to acute respiratory distress syndrome (ARDS) and bronchopulmonary dysplasia (BPD). We have previously shown that cytomix (lipopolysaccharide (LPS), interleukin (IL)-1ß, interferon-γ, and tumor necrosis factor-α), but not LPS alone, results in robust cell death in human pulmonary microvascular endothelial cells (hPMVEC). We hypothesized that the inflammatory cascade associated with cytomix treatment in hPMVEC would result in the release of HMGB1, a damage-associated molecular pattern (DAMP), which would enhance the pro-inflammatory response. Treatment of hPMVEC with cytomix for 24 hours resulted in a robust (25-fold) induction of HMGB1 protein levels in the media compared to controls. Cytomix treatment of hPMVEC resulted in nearly 5-fold greater cleaved caspase-1 protein levels and nearly 60-fold greater cleaved IL-1ß protein levels than in control hPMVEC. Viable hPMVEC numbers were significantly reduced after cytomix treatment. To assess the role of TLR4 in the inflammatory response of hPMVEC following cytomix treatment, we utilized TAK-242, a TLR4 antagonist. The cytomix-induced increase in media HMGB1 levels was significantly attenuated by TAK-242. TAK-242 also significantly attenuated the cytomix-induced increases in cleaved caspase-1 and cleaved IL-1ß. To assess the role of caspase 1 in the inflammatory response of hPMVEC following cytomix treatment, we utilized Ac-YVAD-CMK, a caspase-1 antagonist. Treatment with Ac-YVAD-CMK attenuated the cytomix-induced increase in media HMGB1 and cleaved IL-1ß; and partially restored viable cell numbers following cytomix treatment. To further understand the role of HMGB1 in the pro-inflammatory process we treated hPMVEC with an HMGB1 antibody; and found that the HMGB1 antibody significantly attenuated the increases in HMGB1 and cleaved IL-1ß release, as well as endothelial cell death caused by cytomix treatment. Our results demonstrate that treatment with cytomix results in release of HMGB1, which activates caspase 1 leading to greater HMGB1 production. Furthermore, HMGB1 activation of caspase-1 leads to cleaved IL-1ß production as well as hPMVEC death. Preventing the interaction of HMGB1 and TLR4 attenuated HMGB1 and cleaved IL-1ß release, and attenuated cytomix-induced reductions in viable cell numbers. We speculate that the release of damage-associated molecular patterns (DAMPs), such as HMGB1, may be crucial in the innate immune response of hPMVECs. These findings may have implications for the pathogenesis of ALI in inflammatory lung diseases.

6.
Front Pharmacol ; 13: 897669, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35571092

RESUMO

Backgroud: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease involving multiple systems with a high prevalence of nephritis and atherosclerosis. Jieduquyuziyin prescription is a famous prescription with immune modulating and inflammation controlling effects, which is efficacious in the treatment of SLE. The most critical herbs in this prescription are Qinghao and Biejia. The aim of this study was to evaluate the therapeutic effect of Qinghao-Biejia herb hair (QB) on mice with SLE combined with atherosclerosis. Materials and Methods: The effect of QB (identification using UPLC-TOF-MS) was assessed in female ApoE-/- mice intraperitoneally injected with 0.5 ml of pristane. Serum autoantibodies and lipid metabolic parameters were tested every 4 weeks, and spleen index, serum inflammatory biomarkers, renal injury, and aortic injury were observed after 16 weeks. The expression of signaling pathway in kidney tissues was observed by RT-qPCR and Western blot. Results: The mice of QB-treated group exhibited a significant reduced serum autoantibodies level, urine protein, and renal immune complex deposition. QB treatment reduced the levels of inflammatory cytokines and improved the renal pathological changes. In addition, there was a reduction in aortic atheromatous plaque and some improvement in dyslipidemia. Moreover, QB suppressed the expression of HMGB1, TLR4, and MyD88 to some extent. Conclusion: The present study implied that QB has clear efficacy for the treatment of SLE combined with atherosclerosis, and that inhibition of the HMGB1/TLR4 signaling pathway may be one of the therapeutic targets of QB for SLE combined with atherosclerosis.

7.
Eur Radiol ; 2022 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-35567603

RESUMO

OBJECTIVES: Immune checkpoint inhibitor (ICI)-associated myocarditis is a potentially fatal complication. Sparse published researches evaluated the prognostic value of cardiovascular magnetic resonance feature tracking (CMR-FT) for ICI-associated myocarditis. METHODS: In the single-center retrospective study, 52 patients with ICI-associated myocarditis and CMR were included from August 2018 to July 2021. The ICI-associated myocarditis was diagnosed by using the clinical criteria of the European Society of Cardiology guidelines. Major adverse cardiovascular events (MACE) were comprised of cardiovascular death, cardiogenic shock, cardiac arrest, and complete heart block. RESULTS: During a median follow-up of 171 days, 14 (27%) patients developed MACE. For patients with MACE, the global circumferential strain (GCS), global radial strain (GRS), global longitudinal strain (GLS), and left ventricular ejection fraction (LVEF) were significantly worse and native T1 values and late gadolinium enhancement (LGE) extent were significantly increased, compared with patients without MACE (p < 0.05). The GLS remained the independent factor associated with a higher risk of MACE (hazard ratio (HR): 2.115; 95% confidence interval (CI): 1.379-3.246; p = 0.001) when adjusting for LVEF, LGE extent, age, sex, body mass index, steroid treatment, and prior cardiotoxic chemotherapy or radiation. After adjustment for LVEF, the GLS remained the independent risk factor associated with a higher rate of MACE among patients with a preserved LVEF (HR: 1.358; 95% CI: 1.007-1.830; p = 0.045). CONCLUSIONS: GLS could provide independent prognostic value over GCS, GRS, traditional CMR features, and clinical features in patients with ICI-associated myocarditis. KEY POINTS: • The global circumferential strain (GCS), global radial strain (GRS), and global longitudinal strain (GLS) by cardiovascular magnetic resonance feature tracking were significantly impaired in patients with an immune checkpoint inhibitor (ICI)-associated myocarditis. • GLS was still significantly impaired in patients with preserved left ventricular ejection fraction. • The worse GLS was an independent risk factor over GCS, GRS, traditional CMR features, and clinical features for predicting major adverse cardiovascular events in patients with ICI-associated myocarditis.

9.
Front Plant Sci ; 13: 858636, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35401614

RESUMO

The goal of agriculture is to optimize the population yield, but natural selection has produced active competition among plants, which decreases population performance. Therefore, cultivar breeding should be based on group selection, increasing yield by weakening individual competitive responses. We hypothesize that this has occurred inadvertently to some degree, so modern cultivars have weakened competitive traits and responses, such as reduced root proliferation in response to neighboring roots. We conducted a field experiment with eight cultivars of spring wheat that have been released over the last hundred years, which we grew at two densities. Two contrasting wheat cultivars, a landrace and a modern cultivar, were used in a second field experiment on competition within and between the two cultivars to quantify their competitiveness. Finally, a greenhouse experiment was conducted with these two cultivars gown (a) in mixture and monoculture, (b) at four densities, (c) two watering levels, and (d) with permeable vs. non-permeable soil dividers, to study root proliferation responses to competition. Results of field experiment 1 showed that the population aboveground biomass (AGB) had increased, while belowground biomass had decreased over the course of breeding, so that the root to shoot ratio (R/S) was negatively correlated with the release year of the cultivar. The landrace had stronger competitiveness than the modern cultivar in the field experiment 2. There was clear evidence of root proliferation and a resultant reduction in AGB in response to neighboring roots in the greenhouse experiment, and the modern variety showed less root proliferation in response to neighbors. We conclude that the newer cultivar was a weaker competitor but higher-yielding in two ways: (1) it had higher reproductive effort and therefore less allocation to structures that increase competitive ability, and (2) it had reduced root proliferation in response to the roots of neighboring plants. Our results show that wheat plants change their biomass allocation in response to resource levels and the presence of neighboring roots. The presence of root proliferation in the modern cultivar, albeit less than in the landrace, suggests that further increases in yield via group selection are possible.

10.
Int J Womens Health ; 14: 583-591, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35479293

RESUMO

Background: Intravasation during transvaginal 4-dimensional hysterosalpingo-contrast sonography (TVS 4D-HyCoSy) may lead to false-negative results in tubal patency evaluation. Although the influencing factors associated with intravasation have been investigated, some factors are only identified during 4D-HyCoSy, thus currently no studies on preventing intravasation. However, several preprocedural features can be collected in advance, which may be valuable in predicting intravasation. Objective: The purpose of this study is to establish a nomogram incorporating the preprocedural features to predict the risk of intravasation before TVS 4D-HyCoSy. Methods: The data of 276 infertile women with patent fallopian tubes were analyzed retrospectively. They were assigned to the study group (n = 62) and the control group (n = 214) according to the development of intravasation. The preprocedural characteristics were collected to investigate the predictors independently associated with intravasation, which were then served as the construction of a nomogram. The performance of the nomogram was verified internally. Results: History of uterine curettage (OR = 2.341, P = 0.009), endometrial thickness (OR = 0.587, P < 0.001), and examination schedule (OR = 0.790, P = 0.024) were found to be the independent influencing factors associated with intravasation. The established nomogram incorporating these preprocedural features was useful for predicting the risk of intravasation prior to 4D-HyCoSy. It yielded net benefits when the predicted probability was less than 50%. Conclusion: The nomogram incorporating the preprocedural characteristics achieved a net benefit for clinical decision-making when the estimated risk was less than 50%. It is recommended to change the examination schedule for patients with an estimated risk greater than 50% and perform 4D-HyCoSy when the risk is less than 50%.

11.
Front Med (Lausanne) ; 9: 827174, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35479954

RESUMO

Frailty is a critical aging-related syndrome but the underlying metabolic mechanism remains poorly understood. The aim of this study was to identify novel biomarkers and reveal potential mechanisms of frailty based on the integrated analysis of metabolome and gut microbiome. In this study, twenty subjects consisted of five middle-aged adults and fifteen older adults, of which fifteen older subjects were divided into three groups: non-frail, pre-frail, and frail, with five subjects in each group. The presence of frailty, pre-frailty, or non-frailty was established according to the physical frailty phenotype (PFP). We applied non-targeted metabolomics to serum and feces samples and used 16S rDNA gene sequencing to detect the fecal microbiome. The associations between metabolites and gut microbiota were analyzed by the Spearman's correlation analysis. Serum metabolic shifts in frailty mainly included fatty acids and derivatives, carbohydrates, and monosaccharides. Most of the metabolites belonging to these classes increased in the serum of frail older adults. Propylparaben was found to gradually decrease in non-frail, pre-frail, and frail older adults. Distinct changes in fecal metabolite profiles and gut microbiota were also found among middle-aged adults, non-frail and frail older subjects. The relative abundance of Faecalibacteriu, Roseburia, and Fusicatenibacter decreased while the abundance of Parabacteroides and Bacteroides increased in frailty. The above altered microbes were associated with the changed serum metabolites in frailty, which included dodecanedioic acid, D-ribose, D-(-)-mannitol, creatine and indole, and their related fecal metabolites. The changed microbiome and related metabolites may be used as the biomarkers of frailty and is worthy of further mechanistic studies.

12.
Front Mol Biosci ; 9: 841209, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35463946

RESUMO

Background: Type 2 diabetes mellitus (T2DM) is a multifaceted disorder affecting epidemic proportion at global scope. Defective insulin secretion by pancreatic ß-cells and the inability of insulin-sensitive tissues to respond effectively to insulin are the underlying biology of T2DM. However, circulating biomarkers indicative of early diabetic onset at the asymptomatic stage have not been well described. We hypothesized that global and targeted mass spectrometry (MS) based metabolomic discovery can identify novel serological metabolic biomarkers specifically associated with T2DM. We further hypothesized that these markers can have a unique pattern associated with latent or early asymptomatic stage, promising an effective liquid biopsy approach for population T2DM risk stratification and screening. Methods: Four independent cohorts were assembled for the study. The T2DM cohort included sera from 25 patients with T2DM and 25 healthy individuals for the biomarker discovery and sera from 15 patients with T2DM and 15 healthy controls for the testing. The Pre-T2DM cohort included sera from 76 with prediabetes and 62 healthy controls for the model training and sera from 35 patients with prediabetes and 27 healthy controls for the model testing. Both global and targeted (amino acid, acylcarnitine, and fatty acid) approaches were used to deep phenotype the serological metabolome by high performance liquid chromatography-high resolution mass spectrometry. Different machine learning approaches (Random Forest, XGBoost, and ElasticNet) were applied to model the unique T2DM/Pre-T2DM metabolic patterns and contrasted with their effectiness to differentiate T2DM/Pre-T2DM from controls. Results: The univariate analysis identified unique panel of metabolites (n = 22) significantly associated with T2DM. Global metabolomics and subsequent structure determination led to the identification of 8 T2DM biomarkers while targeted LCMS profiling discovered 14 T2DM biomarkers. Our panel can effectively differentiate T2DM (ROC AUC = 1.00) or Pre-T2DM (ROC AUC = 0.84) from the controls in the respective testing cohort. Conclusion: Our serological metabolite panel can be utilized to identifiy asymptomatic population at risk of T2DM, which may provide utility in identifying population at risk at an early stage of diabetic development to allow for clinical intervention. This early detection would guide ehanced levels of care and accelerate development of clinical strategies to prevent T2DM.

13.
Hepatobiliary Surg Nutr ; 11(2): 212-226, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35464279

RESUMO

Background: Currently, there are no effective methods for assessing hepatic inflammation without resorting to histological examination of liver tissue obtained by biopsy. T2-weighted images (T2WI) are routinely obtained from liver magnetic resonance imaging (MRI) scan sequences. We aimed to establish a radiomics signature based on T2WI (T2-RS) for assessment of hepatic inflammation in people with nonalcoholic fatty liver disease (NAFLD). Methods: A total of 203 individuals with biopsy-confirmed NAFLD from two independent Chinese cohorts with liver MRI examination were enrolled in this study. The hepatic inflammatory activity score (IAS) was calculated by the unweighted sum of the histologic scores for lobular inflammation and ballooning. One thousand and thirty-two radiomics features were extracted from the localized region of interest (ROI) in the right liver lobe of T2WI and, subsequently, selected by minimum redundancy maximum relevance and least absolute shrinkage and selection operator (LASSO) methods. The T2-RS was calculated by adding the selected features weighted by their coefficients. Results: Eighteen radiomics features from Laplacian of Gaussian, wavelet, and original images were selected for establishing T2-RS. The T2-RS value differed significantly between groups with increasing grades of hepatic inflammation (P<0.01). The T2-RS yielded an area under the receiver operating characteristic (ROC) curve (AUROC) of 0.80 [95% confidence interval (CI): 0.71-0.89] for predicting hepatic inflammation in the training cohort with excellent calibration. The AUROCs of T2-RS in the internal cohort and external validation cohorts were 0.77 (0.61-0.93) and 0.75 (0.63-0.84), respectively. Conclusions: The T2-RS derived from radiomics analysis of T2WI shows promising utility for predicting hepatic inflammation in individuals with NAFLD.

14.
Front Neurol ; 13: 845318, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35386405

RESUMO

Mutations in the SACS gene have been linked to autosomal recessive spastic ataxia of Charlevoix Saguenay (ARSACS). It is a clinically and genetically heterogeneous disease characterized by slow progressive ataxia, spasticity, sensorimotor neuropathy, and a combination of other manifestations, such as lack of spasticity, hearing loss, and epileptic seizures. Currently, there have been very few case reports regarding the SACS gene mutation in Chinese patients. Here, we describe a 35-year-old Chinese patient carrying a novel variant in SACS (c.11486C>T) presenting with progressive ataxia and demyelinating peripheral neuropathy. We then reviewed 22 Chinese cases carrying SACS gene mutations, including our patient. All of them had a cerebellar ataxia gait and showed cerebellar atrophy on brain magnetic resonance imaging (MRI). A total of 28 SACS mutations were identified in these patients. Our study further expands the mutation spectrum of the SACS gene and contributes to the evaluation of genotype-phenotype correlations.

15.
Commun Biol ; 5(1): 326, 2022 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-35388144

RESUMO

Hepatic steatosis is the main characteristic of some liver metabolism diseases. However, unclear molecular mechanism of hepatic steatosis impedes the therapy of this hepatic steatosis. Glutathione-S-transferase mu 2 (GSTM2), as a member of phase II drug metabolizing enzymes (DMEs), regulates cellular antioxidant and detoxificant. GSTM2 was highly up-regulated in hepatic steatosis tissues and high-fat diet (HFD) fed mice. Loss-of-function GSTM2 mouse model demonstrated that GSTM2 protected mice from excess fat accumulation. Mechanistically, GSTM2 interacted with ASK1 and suppressed its phosphorylation and the activation of subsequent downstream p38-JNK signalling. Moreover, GSTM2 overexpression in the liver effectively ameliorated hepatic lipid accumulation. Therefore, we identified GSTM2 as an important negative regulator in progression of hepatic steatosis via both its detoxification/antioxidant and inhibition of ASK1-p38/JNK signalling. This study showed potential therapeutic function of the DME in progression of hepatic steatosis.


Assuntos
Hepatopatia Gordurosa não Alcoólica , Animais , Antioxidantes , Glutationa Transferase/genética , Camundongos , Hepatopatia Gordurosa não Alcoólica/metabolismo
16.
Org Lett ; 24(15): 2858-2862, 2022 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-35394795

RESUMO

An I2-DMSO-mediated cascade reaction using methyl ketones and 1,2,3,4-tetrahydroisoquinolines (THIQs) as commercially available substrates has been developed for the construction of pyrrolo[2,1-a]isoquinoline derivatives. This metal-free process involves N-H/α-C(sp3)-H difunctionalization of THIQ. Two C-C bonds and one C-N bond are formed in one pot under mild conditions. Besides, a quaternary carbon center has been constructed in this transformation efficiently.

17.
Biomed Res Int ; 2022: 5532118, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35378790

RESUMO

Aims: Cryptococcosis is an invasive fungal disease that is associated with an increasing prevalence along with a very high fatality and is primarily caused by Cryptococcus. However, its mechanism to cause pathogenicity is not yet completely understood. In this study, we aim to screen the lncRNA markers in human monocytic (THP-1) cells infected by Cryptococcus neoformans (C. neoformans) through high-throughput sequencing technology and to explore its effects on biological functions. Methods: We initially conducted an lncRNA microarray analysis of the THP-1 cells infected by C. neoformans and normal THP-1 cells. Based upon these data, RT-qPCR was used to verify the expressions of the selected lncRNAs and mRNAs. We then performed functional and pathway enrichment analyses. Lastly, target prediction was performed by using the lncRNA target tool which was based on the differentially expressed lncRNAs. Results: We determined 81 upregulated and 96 downregulated lncRNAs using microarray. In addition, the profiling data showed 42 upregulated and 57 downregulated genes and discovered that neuroactive ligand-receptor interaction, tyrosine metabolism, and phenylalanine metabolism are extremely impaired in the regulation of C. neoformans infection. GO enrichment analysis of the 99 differentially expressed mRNAs exhibited that these modules showed different signaling pathways and biological mechanisms like protein binding and metal ion binding. Moreover, lncRNAs and mRNAs were analyzed for their coexpression relations. A qRT-PCR analysis confirmed that the expression of the top 10 differently expressed mRNA and lincRNA. The expressions of the lncRNAs after C. neoformans infection in THP-1 cells were detected by RNA-sequence, suggesting that microarray analysis could reveal lncRNAs having functional significance that might be linked with the progression of patients. Conclusion: The current study analyzed the differential lncRNAs and mRNAs in C. neoformans infection and predicted the corresponding pathways and their correlations that can offer new potential insights into the mechanistic basis of this condition.


Assuntos
Criptococose , RNA Longo não Codificante , Criptococose/genética , Cryptococcus neoformans , Perfilação da Expressão Gênica , Redes Reguladoras de Genes , Humanos , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Células THP-1
18.
Exp Gerontol ; 163: 111796, 2022 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-35381315

RESUMO

Increased visceral fat is strongly associated with a series of metabolic complications. Postmenopausal women have an increased risk of visceral fat accumulation, metabolic disorders, and a high incidence of cardiovascular events. However, the effect of estrogen replacement therapy on visceral adipose tissue among postmenopausal women of different ages remains controversial, and the underlying mechanism remains unclear. Hence, it is important to understand when estrogen replacement therapy affects the function of visceral adipose tissue (VAT). Therefore, we collected VAT from pre- and post-menopausal females and we observed increased pro-inflammatory cytokines and insulin resistance-inducing factors, decreased insulin-sensitizing factors, and thermogenic factors in VAT of postmenopausal women. The analysis of adipocytes isolated from the VAT of females of different ages indicated that adiponectin and browning signature genes were significantly decreased with estrogen treatment in postmenopausal women, but were not altered in the young group. Estrogen supplementation in aged female mice (22 m) significantly prevented visceral fat accumulation. However, it deteriorated VAT function by inducing pro-inflammatory cytokines and insulin resistance-inducing factors and decreasing insulin-sensitizing and thermogenic factors. Mechanistically, estrogen induced the expression of long non-coding RNA Gas5 via binding ERα in premenopausal women, which therefore suppressed IGF2BP1 to maintain VAT function. After menopause, with the reversal of ERα/ERß ratio in VAT, estrogen supplementation mainly worked through ERß, which led to low expression levels of Gas5 and eventually caused VAT dysfunction. Our study demonstrated the adverse effects of estrogen supplementation on VAT function in aged postmenopausal population and further elucidated the involved mechanism.


Assuntos
Receptor alfa de Estrogênio , Resistência à Insulina , Idoso , Animais , Citocinas/metabolismo , Suplementos Nutricionais , Receptor alfa de Estrogênio/genética , Receptor beta de Estrogênio/metabolismo , Estrogênios/metabolismo , Estrogênios/farmacologia , Feminino , Humanos , Insulina/metabolismo , Gordura Intra-Abdominal/metabolismo , Camundongos , Obesidade Abdominal , Pós-Menopausa
19.
Life Sci ; 299: 120540, 2022 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-35398332

RESUMO

AIMS: In mammals, heat stress (HS) from high-temperature environments has multiple adverse effects on the well-being of the organism. Brown adipose tissue (BAT) is a thermogenesis tissue that protects against obesity, and as an endocrine organ that regulates the systemic metabolism, but it is unclear how heat stress affects BAT in normal and obese subjects. Understanding the transcriptomic profiles and lipidomics of BAT upon heat exposure provides insights into the adaptive changes associated with this process. MATERIALS AND METHODS: We constructed heat treatment (40 °C, 4 h) models for normal and obese mice, observed the effect of heat treatment on interscapular BAT (iBAT) and performed an assay for iBAT with RNA-seq and lipidomics to compare transcriptional programs and lipid dynamics. KEY FINDINGS: In normal mice, heat treatment caused an iBAT damage by decreasing the expression of genes involved in thermogenesis, adipogenesis and lipid metabolism. Furthermore, HS disturbed the acyl-chain composition of triacylglycerols (TAGs) and glycerophospholipids (PEs, PCs and CLs), accelerated the production of cholesterol esters, and caused the formation of giant lipid droplets rich in cholesterol esters in iBAT. Unexpectedly, in obese mice, heat treatment had a smaller effect on iBAT by improving the composition of the saturated glycerolipids, PEs and PCs and increasing the proportion of oxidized lipid in lipid droplets. SIGNIFICANCE: Our findings proved lipid droplets participated in the regulation of lipid components of iBAT in normal and obese mice after heat treatment, which provided a new view for the understanding of the adaptation of iBAT to high-temperature environments.


Assuntos
Tecido Adiposo Marrom , Transcriptoma , Tecido Adiposo Marrom/metabolismo , Animais , Ésteres do Colesterol/metabolismo , Humanos , Gotículas Lipídicas , Lipidômica , Mamíferos , Camundongos , Camundongos Obesos , Obesidade/metabolismo , Termogênese
20.
Diabetes Metab Syndr ; 16(4): 102479, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35427913

RESUMO

BACKGROUND: The use of exogenous insulin exposes the patients to sharps (insulin pen needles and lancets). Improper sharps disposal increases the risk of transmitting diseases such as hepatitis B, hepatitis C, Human Immunodeficiency Virus and other blood borne diseases. AIMS: To assess the knowledge, attitude and practices of sharp disposal among type 2 diabetes mellitus patients in the Northern Peninsular of Malaysia. METHODS: A self-administered, questionnaire-based, cross-sectional study was conducted at nine health clinics in the three Northern Peninsular Malaysia states. This study (NMRR-20-1757-56045 IIR) was approved by Medical Research and Ethics Committee, Malaysia. RESULTS: A total of 312 subjects were recruited in this study. The majority (46.15%) of the subjects had moderate knowledge regarding sharps disposal ranging from 60% to 70% of the knowledge score. The majority (59.60%) of the subjects had a positive attitude towards proper sharps disposal and 13.30% of the subjects had a strongly positive attitude. Sharps disposal practices among type 2 diabetes mellitus patients were poor since only two subjects reported correctly disposing of their used sharps. CONCLUSION: The study showed that the majority of the subjects had moderate knowledge, a positive attitude and poor sharp disposal practice.


Assuntos
Diabetes Mellitus Tipo 2 , Eliminação de Resíduos de Serviços de Saúde , Estudos Transversais , Diabetes Mellitus Tipo 2/epidemiologia , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Insulina , Malásia/epidemiologia
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